FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Poole, EM Shu, XO Caan, BJ Flatt, SW Holmes, MD Lu, W Kwan, ML Nechuta, SJ Pierce, JP Chen, WY AF Poole, Elizabeth M. Shu, XiaoOu Caan, Bette J. Flatt, Shirley W. Holmes, Michelle D. Lu, Wei Kwan, Marilyn L. Nechuta, Sarah J. Pierce, John P. Chen, Wendy Y. TI Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Vitamins; Survival; Mortality ID VITAMIN-D; COLORECTAL-CANCER; POSTMENOPAUSAL WOMEN; 25-HYDROXYVITAMIN D; PROSPECTIVE COHORT; RADIATION-THERAPY; RANDOMIZED-TRIAL; NURSES HEALTH; BETA-CAROTENE; LUNG-CANCER AB Vitamin supplement use after breast cancer diagnosis is common, but little is known about long-term effects on recurrence and survival. We examined postdiagnosis supplement use and risk of death or recurrence in the After Breast Cancer Pooling Project, a consortium of four cohorts of 12,019 breast cancer survivors from the United States and China. Post-treatment supplement use (vitamins A, B, C, D, E, and multivitamins) was assessed 1-5 years postdiagnosis. Associations with risk of recurrence, breast cancer-specific mortality, or total mortality were analyzed in Cox proportional hazards models separately by cohort. Individual cohort results were combined using random effects meta-analysis. Interactions with smoking, treatment, and hormonal status were examined. In multivariate models, vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95 % CI 0.79-0.99), and vitamin C with decreased risk of death (RR: 0.81; 95 % CI 0.72-0.92). However, when supplements were mutually adjusted, all associations were attenuated. There were no statistically significant associations with breast cancer mortality. The use of antioxidant supplements (multivitamins, vitamin C, or E) was not associated with recurrence, but was associated with a 16 % decreased risk of death (95 % CI 0.72-0.99). In addition, vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (p-interaction = 0.01). In this large consortium of breast cancer survivors, post-treatment use of vitamin supplements was not associated with increased risk of recurrence or death. Post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine. Stratification by ER status and considering antioxidants as a group may be more clinically relevant when evaluating associations with cancer risk and mortality. C1 [Poole, Elizabeth M.; Holmes, Michelle D.; Chen, Wendy Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Holmes, Michelle D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Shu, XiaoOu; Nechuta, Sarah J.] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA. [Shu, XiaoOu] Shanghai Inst Prevent Med, Shanghai, Peoples R China. [Caan, Bette J.; Kwan, Marilyn L.] Kaiser Permanente, Div Res, Oakland, CA USA. [Flatt, Shirley W.; Pierce, John P.] Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, San Diego, CA 92103 USA. [Lu, Wei] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Poole, EM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. EM nhlip@channing.harvard.edu OI Poole, Elizabeth/0000-0002-4680-4587 FU National Institutes of Health [R01 CA118229-03S1, R01 CA118229, R01 CA129059, P01 CA87969, T32 CA009001]; U.S. Army Medical Research and Materiel Command [DAMD 17-02-1-0607]; Susan G. Komen for the Cure [KG100988] FX The NHS thanks the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. This study was supported by the National Institutes of Health (R01 CA118229-03S1, R01 CA118229, R01 CA129059, P01 CA87969, and T32 CA009001); the U.S. Army Medical Research and Materiel Command (DAMD 17-02-1-0607); and Susan G. Komen for the Cure (KG100988). NR 34 TC 10 Z9 10 U1 2 U2 11 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 JUN PY 2013 VL 139 IS 2 BP 529 EP 537 DI 10.1007/s10549-013-2548-4 PG 9 WC Oncology SC Oncology GA 173HM UT WOS:000321069600023 PM 23660948 ER PT J AU Biswas, S Atienza, P Chipman, J Hughes, K Barrera, AMG Amos, CI Arun, B Parmigiani, G AF Biswas, Swati Atienza, Philamer Chipman, Jonathan Hughes, Kevin Barrera, Angelica M. Gutierrez Amos, Christopher I. Arun, Banu Parmigiani, Giovanni TI Simplifying clinical use of the genetic risk prediction model BRCAPRO SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BRCA2; Genetic counseling; FHAT; CancerGene; BRCAPRO; HughesRiskApps; Genetic risk ID CARRIER PROBABILITY ESTIMATION; OVARIAN-CANCER; FAMILY-HISTORY; BREAST; MUTATIONS; MANAGEMENT; MARKERS; WOMEN AB Health care providers need simple tools to identify patients at genetic risk of breast and ovarian cancers. Genetic risk prediction models such as BRCAPRO could fill this gap if incorporated into Electronic Medical Records or other Health Information Technology solutions. However, BRCAPRO requires potentially extensive information on the counselee and her family history. Thus, it may be useful to provide simplified version(s) of BRCAPRO for use in settings that do not require exhaustive genetic counseling. We explore four simplified versions of BRCAPRO, each using less complete information than the original model. BRCAPROLYTE uses information on affected relatives only up to second degree. It is in clinical use but has not been evaluated. BRCAPROLYTE-Plus extends BRCAPROLYTE by imputing the ages of unaffected relatives. BRCAPRO-LYTE-Simple reduces the data collection burden associated with BRCAPROLYTE and BRCAPROLYTE-Plus by not collecting the family structure. BRCAPRO-1Degree only uses first-degree affected relatives. We use data on 2,713 individuals from seven sites of the Cancer Genetics Network and MD Anderson Cancer Center to compare these simplified tools with the Family History Assessment Tool (FHAT) and BRCAPRO, with the latter serving as the benchmark. BRCAPROLYTE retains high discrimination; however, because it ignores information on unaffected relatives, it overestimates carrier probabilities. BRCAPROLYTE-Plus and BRCAPROLYTE-Simple provide better calibration than BRCAPROLYTE, so they have higher specificity for similar values of sensitivity. BRCAPROLYTE-Plus performs slightly better than BRCAPROLYTE-Simple. The Areas Under the ROC curve are 0.783 (BRCAPRO), 0.763 (BRCAPROLYTE), 0.772 (BRCAPROLYTE-Plus), 0.773 (BRCAPROLYTE-Simple), 0.728 (BRCAPRO-1Degree), and 0.745 (FHAT). The simpler versions, especially BRCAPROLYTE-Plus and BRCAPROLYTE-Simple, lead to only modest loss in overall discrimination compared to BRCAPRO in this dataset. Thus, we conclude that simplified implementations of BRCAPRO can be used for genetic risk prediction in settings where collection of complete pedigree information is impractical. C1 [Biswas, Swati] Univ Texas Dallas, Dept Math Sci, Richardson, TX 75080 USA. [Atienza, Philamer] Univ N Texas, Dept Biostat, Sch Publ Hlth, Hlth Sci Ctr, Ft Worth, TX USA. [Atienza, Philamer] Alcon Res Ltd, Ft Worth, TX USA. [Chipman, Jonathan; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hughes, Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barrera, Angelica M. Gutierrez; Arun, Banu] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol & Clin Canc Genet, Houston, TX 77030 USA. [Amos, Christopher I.] Dartmouth Coll, Geisel Coll Med, Dept Community & Family Med, Hanover, NH 03755 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Biswas, S (reprint author), Univ Texas Dallas, Dept Math Sci, FO 35,800 West Campbell Rd, Richardson, TX 75080 USA. EM swati.biswas@utdallas.edu OI Hughes, Kevin/0000-0003-4084-6484 FU Susan G Komen [KG081303]; National Cancer Institute [1R03CA173834-01, 2P30CA006516-47]; Dana Farber Cancer Institute FX This work was supported in part by Susan G Komen Grant KG081303, National Cancer Institute Grants 1R03CA173834-01 and 2P30CA006516-47 and the Dana Farber Cancer Institute. NR 19 TC 8 Z9 8 U1 0 U2 10 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 JUN PY 2013 VL 139 IS 2 BP 571 EP 579 DI 10.1007/s10549-013-2564-4 PG 9 WC Oncology SC Oncology GA 173HM UT WOS:000321069600027 PM 23690142 ER PT J AU Freedman, RA Pitcher, B Keating, NL Ballman, KV Mandelblatt, J Kornblith, AB Kimmick, GG Hurria, A Winer, EP Hudis, CA Cohen, HJ Muss, HB AF Freedman, Rachel A. Pitcher, Brandelyn Keating, Nancy L. Ballman, Karla V. Mandelblatt, Jeanne Kornblith, Alice B. Kimmick, Gretchen G. Hurria, Arti Winer, Eric P. Hudis, Clifford A. Cohen, Harvey Jay Muss, Hyman B. CA Alliance Clinical Trials Oncology TI Cognitive function in older women with breast cancer treated with standard chemotherapy and capecitabine on Cancer and Leukemia Group B 49907 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Cognitive function; Older women; Breast cancer; Age ID RECEIVING ADJUVANT CHEMOTHERAPY; MENOPAUSAL SYMPTOMS; DOSE CHEMOTHERAPY; FOLLOW-UP; SURVIVORS; IMPAIRMENT; FATIGUE; ADULTS; QUESTIONNAIRE; METAANALYSIS AB Cognitive changes in older women receiving chemotherapy are poorly understood. We examined self-reported cognitive function for older women who received adjuvant chemotherapy on Cancer and Leukemia Group B (CALGB) 49907. CALGB 49907 randomized 633 women aged >= 65 with stage I-III breast cancer to standard adjuvant chemotherapy (cyclophosphamide-methotrexate-5-fluorouracil or doxorubicin-cyclophosphamide) versus capecitabine. We examined self-reported cognitive function in 297 women (CALGB 361002) who enrolled on the quality of life substudy and had no gross impairment on cognitive screening. Women were evaluated using an 18-item instrument at six time points (baseline through 24 months). At each time point for each patient, we calculated a cognitive function score (CFS) defined as themean response of items 1-18 and defined impairment as a score >1.5 standard deviations above the overall average baseline score. Differences in scores by patient characteristics were evaluated using a Kruskal-Wallis test. A linear mixed-effects model was used to assess CFSs by treatment over time. Among 297 women, the median age was 71.5 (range 65-85) and 73 % had performance status of 0. Baseline depression and fatigue were reported in 6 and 14 % of patients, respectively. The average CFS at baseline was 2.08 (corresponding to "normal ability"), and baseline cognitive function did not differ by treatment regimen (p = 0.350). Over 24 months, women reported minimal changes at each time point and insignificant differences by treatment arm were observed. In a healthy group of older women, chemotherapy was not associated with longitudinal changes in self-reported cognitive function. C1 [Freedman, Rachel A.; Kornblith, Alice B.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Pitcher, Brandelyn] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Ballman, Karla V.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. [Mandelblatt, Jeanne] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Kimmick, Gretchen G.] Duke Med Oncol, Durham, NC USA. [Hurria, Arti] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Hurria, Arti] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA. [Hudis, Clifford A.] Mem Sloan Kettering, Dept Med Oncol, New York, NY USA. [Cohen, Harvey Jay] Duke Med Oncol, Ctr Study Aging, Durham, NC USA. [Muss, Hyman B.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org OI Ballman, Karla/0000-0002-4492-0357 FU Celgene through Cancer and Leukemia Group B Foundation; National Cancer Institute at the National Institutes of Health [U10 CA 84131, CA 127617, CA096940, CA129769, CA31946, CA33601]; National Institute on Aging at the National Institutes of Health [CA85850] FX We thank all of the breast cancer patients who shared their experiences while participating in this study. We also thank Dr. Andrew Saykin for his guidance in using his cognitive function measure and Jacqueline Lafky for her administrative and logistical support. We acknowledge support from Celgene provided through the Cancer and Leukemia Group B Foundation Young Investigator Award [RF]. This research was also supported in part by the National Cancer Institute at the National Institutes of Health [Grant # U10 CA 84131, CA 127617, CA096940, and CA129769 to JSM] and by the National Institute on Aging at the National Institutes of Health [Grant #CA85850 to HM]. The research for CALGB 49907 was also supported, in part, by the National Cancer Institute at the National Institutes of Health [Grant # CA31946 to the Cancer and Leukemia Group B (Monica Bernagnoli, MD, Chairman) and Grant # CA33601 to the CALGB Statistical Center (Stephen George, PhD)]. NR 42 TC 8 Z9 8 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 JUN PY 2013 VL 139 IS 2 BP 607 EP 616 DI 10.1007/s10549-013-2562-6 PG 10 WC Oncology SC Oncology GA 173HM UT WOS:000321069600031 PM 23681403 ER PT J AU Gainor, JF Shaw, AT AF Gainor, Justin F. Shaw, Alice T. TI The New Kid on the Block: RET in Lung Cancer SO CANCER DISCOVERY LA English DT Editorial Material ID FUSIONS; IDENTIFICATION; GENE; ADENOCARCINOMA; MUTATIONS; GEFITINIB; KIF5B-RET; ALK AB RET has recently been identified as a potential new oncogenic driver in a subset of patients with non-small cell lung cancer (NSCLC). In this issue of Cancer Discovery, Drilon and colleagues report preliminary trial data with a RET inhibitor in RET fusion-positive NSCLC, validating RET as a therapeutic target in lung cancer. C1 [Gainor, Justin F.; Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org NR 15 TC 6 Z9 6 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JUN PY 2013 VL 3 IS 6 BP 604 EP 606 DI 10.1158/2159-8290.CD-13-0174 PG 3 WC Oncology SC Oncology GA 180RV UT WOS:000321614100015 PM 23749525 ER PT J AU Killian, JK Kim, SY Miettinen, M Smith, C Merino, M Tsokos, M Quezado, M Smith, WI Jahromi, MS Xekouki, P Szarek, E Walker, RL Lasota, J Raffeld, M Klotzle, B Wang, ZF Jones, L Zhu, YL Wang, YH Waterfall, JJ O'Sullivan, MJ Bibikova, M Pacak, K Stratakis, C Janeway, KA Schiffman, JD Fan, JB Helman, L Meltzer, PS AF Killian, J. Keith Kim, Su Young Miettinen, Markku Smith, Carly Merino, Maria Tsokos, Maria Quezado, Martha Smith, William I., Jr. Jahromi, Mona S. Xekouki, Paraskevi Szarek, Eva Walker, Robert L. Lasota, Jerzy Raffeld, Mark Klotzle, Brandy Wang, Zengfeng Jones, Laura Zhu, Yuelin Wang, Yonghong Waterfall, Joshua J. O'Sullivan, Maureen J. Bibikova, Marina Pacak, Karel Stratakis, Constantine Janeway, Katherine A. Schiffman, Joshua D. Fan, Jian-Bing Helman, Lee Meltzer, Paul S. TI Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence in Gastrointestinal Stromal Tumor SO CANCER DISCOVERY LA English DT Article ID OF-FUNCTION MUTATIONS; IDH2 MUTATIONS; COPY-NUMBER; KIT; SUPPRESSORS; INHIBITION; HISTONE; UPDATE; ASSAY; SDHA AB Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance. SIGNIFICANCE: This study shows that SDH deficiency underlies pervasive DNA hypermethylation in multiple tumor lineages, generally defining the Krebs cycle as mitochondrial custodian of the methylome. We propose that this phenomenon may result from a failure of maintenance CpG demethylation, secondary to inhibition of the TET 5-methylcytosine dioxgenase demethylation pathway, by inhibitory metabolites that accumulate in tumors with Krebs cycle dysfunction. (c) 2013 AACR. C1 [Killian, J. Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Walker, Robert L.; Lasota, Jerzy; Raffeld, Mark; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J.; Helman, Lee; Meltzer, Paul S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Smith, William I., Jr.] Suburban Hosp, Bethesda, MD USA. [Xekouki, Paraskevi; Szarek, Eva; Pacak, Karel; Stratakis, Constantine] Eunice Kennedy Shriver NICHD, Bethesda, MD USA. [Jahromi, Mona S.; Schiffman, Joshua D.] Univ Utah, Salt Lake City, UT USA. [Klotzle, Brandy; Bibikova, Marina; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA. [Janeway, Katherine A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Sullivan, Maureen J.] Our Ladys Childrens Hosp, Dublin, Ireland. RP Meltzer, PS (reprint author), NCI, Genet Branch, 37 Convent Dr MSC 4265, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov FU Intramural Research Program of NIH; National Cancer Institute; Center for Cancer Research FX This work was supported by grants from the Intramural Research Program of NIH, the National Cancer Institute, and the Center for Cancer Research. NR 26 TC 105 Z9 109 U1 1 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JUN PY 2013 VL 3 IS 6 BP 648 EP 657 DI 10.1158/2159-8290.CD-13-0092 PG 10 WC Oncology SC Oncology GA 180RV UT WOS:000321614100022 PM 23550148 ER PT J AU Lum, G AF Lum, Gifford TI Severe Hyponatremia in a Schizophrenic Patient SO CLINICAL CHEMISTRY LA English DT Editorial Material ID BEER-DRINKERS; POTOMANIA C1 VA Boston Healthcare Syst, Boston, MA 02132 USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM gifford.lum@va.gov NR 10 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2013 VL 59 IS 6 BP 887 EP 889 DI 10.1373/clinchem.2012.194969 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 179VC UT WOS:000321548500005 PM 23719823 ER PT J AU Udell, JA Morrow, DA Braunwald, E Swedberg, K Bode, C Rifai, N Brunel, PC Prescott, MF Ren, F Hoffman, EB Scirica, BM AF Udell, Jacob A. Morrow, David A. Braunwald, Eugene Swedberg, Karl Bode, Christoph Rifai, Nader Brunel, Patrick C. Prescott, Margaret F. Ren, Fang Hoffman, Elaine B. Scirica, Benjamin M. TI Inhibition of the Renin-Angiotensin System Reduces the Rise in Serum Aldosterone in Acute Coronary Syndrome Patients with Preserved Left Ventricular Function: Observations from the AVANT GARDE-TIMI 43 Trial SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; NATRIURETIC-PEPTIDE; HEART-FAILURE; ORAL CAPTOPRIL; DYSFUNCTION; MORTALITY; MORBIDITY; SURVIVAL; ACTIVATION; EXTRACTION AB BACKGROUND: Acute coronary syndrome (ACS) activates neurohormonal pathways, including elevations in circulating aldosterone, with deleterious cardiovascular effects. We aimed to determine if early, more complete renin-angiotensin-aldosterone system inhibition (RAASI) in post-ACS patients without ventricular dysfunction or heart failure would result in a graded reduction in aldosterone concentrations. METHODS: We performed serial measurement of serum aldosterone within the Aliskiren and Valsartan to Reduce NT-proBNP via Renin-Angiotensin-Aldosterone-System Blockade (AVANT GARDE)-Thrombolysis in Myocardial Infarction (TIMI) 43 trial, a randomized double-blind, placebo controlled trial of RAASI by valsartan, aliskiren, or both in post-ACS patients with preserved ventricular function but increased natriuretic peptides. Aldosterone was measured at randomization and week 8. RESULTS: Median aldosterone concentrations were comparable across treatment arms at baseline (9.26 ng/dL; interquartile range 7.12-12.76; n = 1073). In the placebo group, there was a significant increase in aldosterone over 8 weeks (19.7% rise, 2.20 (0.36) ng/dL, P < 0.0001) that was significantly reduced across active RAASI therapies (1.36 (0.39) ng/dL with aliskiren; 1.02 (0.37) ng/dL with valsartan; and 0.85 (0.37) ng/dL with combination therapy, P trend = 0.008). Compared to placebo, RAASI monotherapy resulted in a pooled relative absolute aldosterone change of -1.01 (0.45) ng/dL (P < 0.026 vs placebo), and combination therapy resulted in a relative absolute aldosterone change of -1.35 (0.52) ng/dL (P = 0.01 vs placebo). No significant difference in aldosterone concentrations was achieved between dual vs single RAASI (P = 0.47). CONCLUSIONS: In ACS patients with preserved ventricular function but increased natriuretic peptides, serum aldosterone rises over time and is blunted by more complete RAASI. The clinical implications and role for RAASI in this population warrant further investigation. (C) 2013 American Association for Clinical Chemistry C1 [Udell, Jacob A.; Morrow, David A.; Braunwald, Eugene; Ren, Fang; Hoffman, Elaine B.; Scirica, Benjamin M.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Udell, Jacob A.; Morrow, David A.; Braunwald, Eugene; Hoffman, Elaine B.; Scirica, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Udell, Jacob A.] Womens Coll Hosp, Dept Med, Cardiovasc Div, Toronto, ON, Canada. [Udell, Jacob A.] Univ Toronto, Toronto, ON, Canada. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Emergency & Cardiovasc Med, Gothenburg, Sweden. [Bode, Christoph] Med Univ Klin, Dept Internal Med Cardiol, Freiburg, Germany. [Rifai, Nader] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Brunel, Patrick C.] Novartis Pharma AG, Clin Dev & Med Affairs, Basel, Switzerland. [Prescott, Margaret F.] Novartis Pharmaceut, Clin Dev & Med Affairs, E Hanover, NJ USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU Novartis Pharmaceuticals; Roche Diagnostics; Novartis; Bayer; Medtronic; Sanofi-Aventis FX AVANT GARDE-TIMI 43 was supported by a research grant to the TIMI Study Group from Novartis Pharmaceuticals. Reagents for NT-proBNP were provided via an unrestricted grant from Roche Diagnostics. D.A. Morrow, Novartis; K. Swedberg, Novartis; C. Bode, Bayer, Medtronic, and Sanofi-Aventis. NR 39 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2013 VL 59 IS 6 BP 959 EP 967 DI 10.1373/clinchem.2012.199729 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 179VC UT WOS:000321548500015 PM 23509108 ER PT J AU Kang, JX Gleason, ED AF Kang, Jing X. Gleason, Erin D. TI Omega-3 Fatty Acids and Hippocampal Neurogenesis in Depression SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Depression; docosahexaenoic acid (DHA); fat-1 mouse; hippocampus; neurogenesis; omega-3 fatty acids ID POLYUNSATURATED FATTY-ACID; PLACEBO-CONTROLLED TRIAL; BLOOD-CELL MEMBRANES; DOCOSAHEXAENOIC ACID; MAJOR DEPRESSION; DOUBLE-BLIND; FISH CONSUMPTION; FAT-1 MICE; EICOSAPENTAENOIC ACID; TRANSGENIC MICE AB The mammalian brain and central nervous system are especially dependent on the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA) for normative signaling and function, and research suggests that n-3 fatty acid deficiencies are one contributing factor in the increasing prevalence of depressive disorders. However, the reasons for which n-3 fatty acids and mood are connected remain unknown. Atrophy in the hippocampus is one of the most significant neuroanatomical findings in depressed patients, and current therapies for depression tend to increase hippocampal neurogenesis. We recently discovered that the fat-1 transgenic mouse, which has enriched levels of DHA in the brain because it can convert n-6 to n-3 fatty acids, exhibits increased hippocampal neurogenesis. This finding suggests a mechanism by which omega-3 could influence depression and mood; here we expand on the argument that n-3 fatty acids, and DHA in particular, may help prevent and treat depression by virtue of their effects on neurogenesis in the hippocampus. Because DHA can be obtained through the diet, increasing DHA intake in depressed patients or those at risk for depression may be one way of managing the disease and perhaps providing aid to those who have not been able to achieve remission via pharmacological means. C1 Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM jxkang@partners.org NR 60 TC 13 Z9 13 U1 2 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD JUN PY 2013 VL 12 IS 4 BP 460 EP 465 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 173UY UT WOS:000321108000004 PM 23574158 ER PT J AU Race, E Keane, MM Verfaellie, M AF Race, Elizabeth Keane, Margaret M. Verfaellie, Mieke TI Living in the moment: Patients with MTL amnesia can richly describe the present despite deficits in past and future thought SO CORTEX LA English DT Letter ID THINKING; MEMORY C1 [Race, Elizabeth; Keane, Margaret M.; Verfaellie, Mieke] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Race, Elizabeth; Keane, Margaret M.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02130 USA. [Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA. RP Race, E (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 150 S Huntington Ave 151-A, Boston, MA 02130 USA. EM race@bu.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [R01 MH093431]; NINDS NIH HHS [F32 NS073212] NR 5 TC 5 Z9 6 U1 0 U2 5 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD JUN PY 2013 VL 49 IS 6 BP 1764 EP 1766 DI 10.1016/j.cortex.2013.02.010 PG 3 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 174PZ UT WOS:000321169200025 PM 23535365 ER PT J AU Shen, L Zhang, Y AF Shen, Li Zhang, Yi TI 5-Hydroxymethylcytosine: generation, fate, and genomic distribution SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; ACTIVE DNA DEMETHYLATION; HOST-INDUCED MODIFICATION; DEOXYRIBONUCLEIC ACID; BASE-RESOLUTION; MAMMALIAN DNA; TET PROTEINS; 5-METHYLCYTOSINE; METHYLATION; 5-CARBOXYLCYTOSINE AB 5-Methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) in mammalian cells by the ten-eleven translocation (Tet) family of dioxygenases. While 5mC has been extensively studied, we have just started to understand the distribution and function of 5hmC in mammalian genomes. Despite the fact that this new epigenetic mark has only been discovered three years ago, exciting progress has been made in understanding its generation, fate, and genomic distribution. In this review we discuss these progresses as well as the recent advance in the single-base resolution mapping of 5hmC. C1 [Shen, Li; Zhang, Yi] Howard Hughes Med Inst, Boston, MA 02115 USA. [Shen, Li; Zhang, Yi] Program Cellular & Mol Med, Boston, MA 02115 USA. [Shen, Li; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Howard Hughes Med Inst, WAB 149G,200 Longwood Av, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu FU HHMI; NIH [U01DK089565] FX We thank Diana Cai and Dr Hao Wu for critical reading of the manuscript. This work was supported by HHMI and NIH (U01DK089565). Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 59 TC 50 Z9 51 U1 2 U2 31 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2013 VL 25 IS 3 BP 289 EP 296 DI 10.1016/j.ceb.2013.02.017 PG 8 WC Cell Biology SC Cell Biology GA 177ZF UT WOS:000321413200003 PM 23498661 ER PT J AU Beverly, EA Fitzgerald, S Sitnikov, L Ganda, OP Caballero, AE Weinger, K AF Beverly, Elizabeth A. Fitzgerald, Shane Sitnikov, Lilya Ganda, Om P. Caballero, A. Enrique Weinger, Katie TI Do Older Adults Aged 60-75 Years Benefit From Diabetes Behavioral Interventions? SO DIABETES CARE LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS; SELF-CARE; GLYCEMIC CONTROL; EDUCATIONAL INTERVENTIONS; META-ANALYSIS; MANAGEMENT; MELLITUS; METAANALYSIS; COMPLICATIONS AB OBJECTIVE-In this secondary analysis, we examined whether older adults with diabetes (aged 60-75 years) could benefit from self-management interventions compared with younger adults. Seventy-one community-dwelling older adults and 151 younger adults were randomized to attend a structured behavioral group, an attention control group, or one-to-one education. RESEARCH DESIGN AND METHODS-We measured AlC, self-care (3-day pedometer readings, blood glucose checks, and frequency of self-care), and psychosocial factors (quality of life, diabetes distress, frustration with self-care, depression, self-efficacy, and coping styles) at baseline and 3, 6, and 12 months postintervention. RESULTS-Both older (age 67 +/- 5 years, AlC 8.7 +/- 0.8%, duration 20 +/- 12 years, 30% type 1 diabetes, 83% white, 41% female) and younger (age 47 +/- 9 years, AlC 9.2 +/- 1.2%, 18 +/- 12 years with diabetes, 59% type 1 diabetes, 82% white, 55% female) adults had improved AlC equally overtime. Importantly, older and younger adults in the group conditions improved more and maintained improvements at 12 months (older structured behavioral group change in AlC -0.72 +/- 1.4%, older control group -0.65 +/- 0.9%, younger behavioral group -0.55 +/- 1.2%, younger control group -0.43 +/- 1.7%). Furthermore, frequency of self-care, glucose checks, depressive symptoms, quality of life, distress, frustration with self-care, self-efficacy, and emotional coping improved in older and younger participants at follow-up. CONCLUSIONS-The findings suggest that, compared with younger adults, older adults receive equal glycemic benefit from participating in self-management interventions. Moreover, older adults showed the greatest glycemic improvement in the two group conditions. Clinicians can safely recommend group diabetes interventions to community-dwelling older adults with poor glycemic control. C1 [Beverly, Elizabeth A.; Fitzgerald, Shane; Sitnikov, Lilya; Ganda, Om P.; Caballero, A. Enrique; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, Elizabeth A.; Ganda, Om P.; Caballero, A. Enrique; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Sitnikov, Lilya] Univ Vermont, Burlington, VT USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU National Institutes of Health (NIH) [R01-DK-060115]; Diabetes and Endocrinology Research Core NIH [P30-DK-36836]; NIH [T32-DK-007260]; Merck; Abbott; GlaxoSmithKline; Bristol-Myers Squibb; AstraZeneca; Daiichi-Sankyo FX This work was supported by National Institutes of Health (NIH) Grant R01-DK-060115 (to K.W.), Diabetes and Endocrinology Research Core NIH Grant P30-DK-36836, and NIH Training Grant T32-DK-007260. The following companies contributed glucose meters and test strips: Abbott Laboratories (Abbott Park, IL), Life Scan (Milpitas, CA), and Roche Diagnostics (Indianapolis, IN). O.P.G. has provided consulting services to Abbott; received payment for lectures from Merck, Abbott, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, and Daiichi-Sankyo; and has stock options with Bristol-Myers Squibb. A.E.C. serves on the advisory panels of the following companies: Eli Lilly and Company; Amylin Pharmaceuticals, Inc.; Takeda Pharmaceuticals America, Inc; sanofi-aventis; and Daiichi-Sankyo. No other potential conflicts of interest relevant to this article were reported. NR 40 TC 12 Z9 12 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2013 VL 36 IS 6 BP 1501 EP 1506 DI 10.2337/dc12-2110 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UJ UT WOS:000321472600012 PM 23315603 ER PT J AU Lacroix, M Battista, MC Doyon, M Menard, J Ardilouze, JL Perron, P Hivert, MF AF Lacroix, Marilyn Battista, Marie-Claude Doyon, Myriam Menard, Julie Ardilouze, Jean-Luc Perron, Patrice Hivert, Marie-France TI Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus SO DIABETES CARE LA English DT Article ID GLUCOSE-TOLERANCE; LIPID-METABOLISM; SENSITIVITY; WOMEN; RECOMMENDATIONS; HYPERGLYCEMIA; SECRETION; ALPHA AB OBJECTIVE-To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, beta-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. RESEARCH DESIGN AND METHODS-We performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), beta-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC(insulin/glucose)), and beta-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay. RESULTS-Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 +/- 3.84 vs. 11.92 +/- 4.59 mu g/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 mu g/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA(1c) at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = -0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC(insulin/glucose). CONCLUSIONS-Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements. C1 [Lacroix, Marilyn; Battista, Marie-Claude; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France] Univ Sherbrooke, Fac Med, Sherbrooke, PQ, Canada. [Doyon, Myriam; Menard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France] CHU Sherbrooke, Ctr Rech Clin Etienne Le Bel, Sherbrooke, PQ J1H 5N4, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Univ Sherbrooke, Fac Med, Sherbrooke, PQ, Canada. EM marie-france.hivert@usherbrooke.ca FU Fonds de la Recherche en Sante du Quebec (FRSQ); Diabete Quebec; Canadian Diabetes Association; Institute of Genetics-Canadian Institute of Health Research (CIHR) FX The study was supported by a Fonds de la Recherche en Sante du Quebec (FRSQ) operating grant (to M.-F.H.) and by Diabete Quebec (to P.P.). M.-F.H. is an FRSQ research scholar and was awarded a Clinical Scientist Award by the Canadian Diabetes Association and the Maud Menten Award from the Institute of Genetics-Canadian Institute of Health Research (CIHR). J.-L.A. is a CIHR scholar (New Investigator award). M.L. was supported by Diabete Quebec. Clinical assessments were performed at the Clinical Research Center Etienne-Le Bel (CRCEL) affiliated with the CHUS; the CRCEL is an FRSQ-supported research center. NR 30 TC 34 Z9 36 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2013 VL 36 IS 6 BP 1577 EP 1583 DI 10.2337/dc12-1731 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UJ UT WOS:000321472600022 PM 23300287 ER PT J AU Katon, JG Reiber, GE Nelson, KM AF Katon, Jodie G. Reiber, Gayle E. Nelson, Karin M. TI Peripheral Neuropathy Defined by Monofilament Insensitivity and Diabetes Status NHANES 1999-2004 SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; SENSORY NEUROPATHY; PREVALENCE; POLYNEUROPATHY; POPULATION; MELLITUS; FOOT AB OBJECTIVE-To determine whether diabetes status, including prediabetes, is associated with increased risk of peripheral neuropathy as defined by monofilament insensitivity. RESEARCH DESIGN AND METHODS-This study used data from the 1999-2004 National Health and Nutrition Examination Survey (n = 7,818). Peripheral neuropathy was defined as one or more insensate sites detected by a Semmes-Weinstein 10-g monofilament. Generalized linear models were used to directly estimate relative risks (RRs) for the association of diabetes status and peripheral neuropathy. RESULTS-After adjustment compared with no diabetes, prediabetes [RR 1.11(95% CI 0.92-1.34)] and undiagnosed diabetes [1.08 (0.73-1.61)] were associated with modest increases in risk of peripheral neuropathy, and diabetes was associated with a 74% higher risk of peripheral neuropathy [1.74 (1.50-2.01)]. CONCLUSIONS-Diabetes is associated with increased risk of peripheral neuropathy defined by monofilament insensitivity, but prediabetes and undiagnosed diabetes may be associated with only a modest increase in risk. C1 [Katon, Jodie G.; Reiber, Gayle E.; Nelson, Karin M.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Katon, Jodie G.; Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. [Nelson, Karin M.] Vet Affairs Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA. RP Katon, JG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. EM jkaton@uw.edu FU Office of Research and Development; Health Services Research and Development; U.S. Department of Veterans Affairs [TPP 61-026, RCS 98-353] FX This material is based on work supported by the Office of Research and Development, Health Services Research and Development, U.S. Department of Veterans Affairs, including a postdoctoral fellowship to J.G.K. (TPP 61-026) and a Senior Career Scientist Award to G.E.R. (grant RCS 98-353). NR 18 TC 6 Z9 6 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2013 VL 36 IS 6 BP 1604 EP 1606 DI 10.2337/dc12-1102 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UJ UT WOS:000321472600026 PM 23275365 ER PT J AU Copeland, KC Higgins, J El Ghormli, L Delahanty, L Grey, M Kriska, AM Lipman, TH Pyle, L Shepherd, J Hirst, K AF Copeland, Kenneth C. Higgins, Janine El Ghormli, Laure Delahanty, Linda Grey, Margaret Kriska, Andrea M. Lipman, Terri H. Pyle, Laura Shepherd, John Hirst, Kathryn CA TODAY Study Grp TI Treatment Effects on Measures of Body Composition in the TODAY Clinical Trial SO DIABETES CARE LA English DT Article ID SAGITTAL ABDOMINAL DIAMETER; CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS; WAIST CIRCUMFERENCE; GLYCEMIC CONTROL; ANTIHYPERGLYCEMIC AGENTS; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; ADIPOSE-TISSUE; YOUNG-ADULTS AB OBJECTIVE-The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial showed superiority of metformin plus rosiglitazone (M+R) over metformin alone (M), with metformin plus lifestyle (M+L) intermediate in maintaining glycemic control. We report here treatment effects on measures of body composition and their relationships to demographic and metabolic variables including glycemia. RESEARCH DESIGN AND METHODS-Measures of adiposity (BMI, waist circumference, abdominal height, percent and absolute fat, and bone mineral content [BMC] and density [BMD]) were analyzed as change from baseline at 6 and 24 months. RESULTS-Measures of fat accumulation were greatest in subjects treated with M+R and least in M+L. Although fat measures in M+L were less than those of M+R and M at 6 months, differences from M were no longer apparent at 24 months, whereas differences from M+R persisted at 24 months. The only body composition measure differing by race and/or ethnicity was waist circumference, greater in M+R than either M or M+L at both 6 and 24 months in whites. BMD and BMC increased in all groups, but increased less in M+R compared with the other two groups by 24 months. Measures of adiposity (increases in BMI, waist circumference, abdominal height, and fat) were associated with reduced insulin sensitivity and increased hemoglobin A(1c) (HbA(1c)), although effects of adiposity on HbA(1c) were less evident in those treated with M+R. CONCLUSIONS-Despite differential effects on measures of adiposity (with M+R resulting in the most and M+L in the least fat accumulation), group differences generally were small and unrelated to treatment effects in sustaining glycemic control. C1 [Copeland, Kenneth C.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Higgins, Janine] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. [El Ghormli, Laure; Pyle, Laura; Hirst, Kathryn] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. [Delahanty, Linda] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Grey, Margaret] Yale Univ, Sch Nursing, New Haven, CT 06520 USA. [Kriska, Andrea M.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Lipman, Terri H.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Shepherd, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP El Ghormli, L (reprint author), George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. EM elghorml@bsc.gwu.edu OI Kriska, Andrea/0000-0002-3522-0869 FU NIDDK of the National Institutes of Health [U01-DK61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [Washington University School of Medicine] [M01RR-00036]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [Children's Hospital Los Angeles] [M01-RR-00043-45]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [University of Colorado Denver] [M01-RR-00069]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [Children's Hospital of Pittsburgh] [M01-RR-00084]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [Massachusetts General Hospital] [M01-RR-01066]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [Yale University] [M01-RR00125]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [University of Oklahoma Health Sciences Center] [M01-RR-14467]; NCRR Clinical and Translational Science Award [Children's Hospital of Philadelphia] [UL1-RR-024134]; NCRR Clinical and Translational Science Award [Yale University] [UL1 -RR024139]; NCRR Clinical and Translational Science Award [Children's Hospital of Pittsburgh] [UL1-RR-024153]; NCRR Clinical and Translational Science Award [Case Western Reserve University] [UL1-RR024989]; NCRR Clinical and Translational Science Award [Washington University in St. Louis] [UL1-RR-024992]; NCRR Clinical and Translational Science Award [Massachusetts General Hospital] [UL1-RR-025758]; NCRR Clinical and Translational Science Award [University of Colorado Denver] [UL1-RR-025780] FX This work was completed with funding from the NIDDK of the National Institutes of Health (grants U01-DK61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254), the National Center for Research Resources (NCRR) General Clinical Research Centers Program (grants M01-RR-00036 [Washington University School of Medicine], M01-RR-00043-45 [Children's Hospital Los Angeles], M01-RR-00069 [University of Colorado Denver], M01-RR-00084 [Children's Hospital of Pittsburgh], M01-RR-01066 [Massachusetts General Hospital], M01-RR00125 [Yale University], and M01-RR-14467 [University of Oklahoma Health Sciences Center]), and the NCRR Clinical and Translational Science Awards (grants UL1-RR-024134 [Children's Hospital of Philadelphia], UL1 -RR024139 [Yale University], UL1-RR-024153 [Children's Hospital of Pittsburgh], UL1-RR024989 [Case Western Reserve University], UL1-RR-024992 [Washington University in St. Louis], UL1-RR-025758 [Massachusetts General Hospital], and UL1-RR-025780 [University of Colorado Denver]). NR 31 TC 7 Z9 7 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2013 VL 36 IS 6 BP 1742 EP 1748 DI 10.2337/dc12-2534 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UJ UT WOS:000321472600048 ER PT J AU Weinstock, RS Caprio, S Copeland, KC Gidding, SS Hirst, K Katz, LL Marcovina, S Nadeau, KJ Nathan, DM AF Weinstock, Ruth S. Caprio, Sonia Copeland, Kenneth C. Gidding, Samuel S. Hirst, Kathryn Katz, Lorraine L. Marcovina, Santica Nadeau, Kristen J. Nathan, David M. CA TODAY Study Grp TI Lipid and Inflammatory Cardiovascular Risk Worsens Over 3 Years in Youth With Type 2 Diabetes The TODAY clinical trial SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE CONTROL; LIPOPROTEIN CHOLESTEROL; LIFE-STYLE; FOLLOW-UP; COMPLICATIONS; ADOLESCENTS; ATHEROSCLEROSIS; PREVENTION; OVERWEIGHT; METFORMIN AB OBJECTIVE-Type 2 diabetes increases cardiovascular risk. We examined lipid profiles and inflammatory markers in 699 youth with recent-onset type 2 diabetes in the TODAY clinical trial and compared changes across treatment groups: metformin alone (M), metformin plus rosiglitazone (M+R), and metformin plus intensive lifestyle program (M+L). RESEARCH DESIGN AND METHODS-Multiethnic youth with type 2 diabetes received M, M+R, or M+L. Statin drugs were begun for LDL cholesterol (LDL) >= 130 mg/dL or triglycerides >= 300 mg/dL. Lipids, apolipoprotein B (apoB), LDL particle size, high-sensitivity c-reactive protein (hsCRP), homocysteine, plasminogen activator inhibitor-1 (PAT-1), and HbA(1c) were measured over 36 months or until loss of glycemic control. RESULTS-LDL, apoB, triglycerides, and non-HDL cholesterol (HDL) rose over 12 months and then stabilized over the next 24 months. Participants with LDL >= 130 mg/dL or using LDL-lowering therapy increased from 4.5 to 10.7% over 36 months, while 55.9% remained at LDL goal (<100 mg/dL) over that time. Treatment group did not impact LDL, apoB, or non-HDL. Small dense LDL (particle size, <= 0.263 relative flotation rate) was most common in M. Triglycerides were lower in M+L than M, and M+L attenuated the negative effect of hyperglycemia on triglycerides and HDL in females. hsCRP, PAI-1, and homocysteine increased over time. However, hsCRP was lower in M+R compared with M or M+L. CONCLUSIONS-Dyslipidemia and chronic inflammation were common in youth with type 2 diabetes and worsened over time. Diabetes treatment, despite some treatment group differences in lipid and inflammatory marker change over time, is generally inadequate to control this worsening risk. C1 [Weinstock, Ruth S.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Caprio, Sonia] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Copeland, Kenneth C.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Hirst, Kathryn] George Washington Univ, Washington, DC 20052 USA. [Katz, Lorraine L.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Nadeau, Kristen J.] Univ Colorado Denver, Denver, CO USA. [Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hirst, K (reprint author), George Washington Univ, Washington, DC 20052 USA. EM khirst@bsc.gwu.edu FU National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health [U01DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research Resources General Clinical Research Centers Program (Washington University School of Medicine) [M01-RR00036]; National Center for Research Resources General Clinical Research Centers Program (Children's Hospital Los Angeles) [M01-RR00043-45]; National Center for Research Resources General Clinical Research Centers Program (University of Colorado Denver) [M01-RR00069]; National Center for Research Resources General Clinical Research Centers Program (Children's Hospital of Pittsburgh) [M01-RR00084, ULI-RR024153]; National Center for Research Resources General Clinical Research Centers Program (Massachusetts General Hospital) [M01-RR01066, UL1-8R025758]; National Center for Research Resources General Clinical Research Centers Program (Yale University) [M01-RR00125, UL1-RR024139]; National Center for Research Resources General Clinical Research Centers Program (University of Oklahoma Health Sciences Center) [M01-RR14467]; National Center for Research Resources Clinical and Translational Science Award (Children's Hospital of Philadelphia) [UL1-RR024134]; National Center for Research Resources General Clinical Research Centers Program (Case Western Reserve University) [UL1RR024989]; National Center for Research Resources General Clinical Research Centers Program (Washington University in St. Louis) [ULI-RR024992]; National Center for Research Resources General Clinical Research Centers Program (University of Colorado Denver [UL1-RR025780]; Eli Lilly and Company; GlaxoSmithKline; Medtronic; AstraZeneca; Daiichi Sankyo FX This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health grants U01DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254; National Center for Research Resources General Clinical Research Centers Program grants M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children's Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and National Center for Research Resources Clinical and Translational Science Awards grants UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), ULI-RR024153 (Children's Hospital of Pittsburgh), UL1RR024989 (Case Western Reserve University), ULI-RR024992 (Washington University in St. Louis), UL1-8R025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver).; R.S.W. is site principal investigator with no salary support for industry-sponsored multicenter clinical trials funded by grants administered through the State University of New York Upstate Medical University from Eli Lilly and Company, GlaxoSmithKline, Medtronic, and AstraZeneca. K.C.C. receives a consulting fee and honorarium as a member of the Steering Committee for a research study conducted by Daiichi Sankyo. S.S.G. has a clinical trial of fish oil for high triglycerides in adolescents funded by GlaxoSmithKline. No other potential conflicts of interest relevant to this article were reported. NR 21 TC 44 Z9 44 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2013 VL 36 IS 6 BP 1758 EP 1764 DI 10.2337/dc12-2388 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UJ UT WOS:000321472600050 ER PT J AU Levitsky, LL Danis, RP Drews, KL Tamborlane, WV Haymond, MW Laffel, L Lipman, TH AF Levitsky, Lynne L. Danis, Ronald P. Drews, Kimberly L. Tamborlane, William V. Haymond, Morey W. Laffel, Lori Lipman, Terri H. CA TODAY Study Grp TI Retinopathy in Youth With Type 2 Diabetes Participating in the TODAY Clinical Trial SO DIABETES CARE LA English DT Article ID PREVALENCE; COHORT; COMPLICATIONS; ADOLESCENTS; PROGRAM AB OBJECTIVE-To determine the prevalence of retinopathy in 517 youth with type 2 diabetes of 2-8 years duration enrolled in the TODAY study. RESEARCH DESIGN AND METHODS-Retinal photographs were graded centrally for retinopathy using established standards. RESULTS-Retinopathy was identified in 13.7% of subjects. Prevalence increased with age, diabetes duration, and mean HbA(1c). Subjects in the highest BMI tertile had the lowest prevalence of retinopathy. CONCLUSIONS-Prevalence of retinopathy and its association with HbA(1c) and diabetes duration is similar to that previously reported in youth with type 1 diabetes and in adults with type 2 diabetes of known duration. The mechanism underlying the reduced risk of retinopathy in the most obese individuals is unknown. Follow-up of this cohort will help define the natural history of retinopathy in youth with type 2 diabetes. C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Danis, Ronald P.] Univ Wisconsin, Madison, WI 53706 USA. [Drews, Kimberly L.] George Washington Univ, Washington, DC 20052 USA. [Tamborlane, William V.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Haymond, Morey W.] Baylor Coll Med, Houston, TX 77030 USA. [Lipman, Terri H.] Childrens Hosp Philadelphia, Philadelphia, PA USA. RP Drews, KL (reprint author), George Washington Univ, Washington, DC 20052 USA. EM kdrews@bsc.gwu.edu FU National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; National Center for Research Resources General Clinical Research Centers Program [M01-RR00036, M01-RR00043-45, M01-RR00069, M01-RR00084, M01-RR01066, M01-RR00125, M01-RR14467]; National Center for Research Resources Clinical and Translational Science Awards [UL1-RR024134, UL1-RR024139, UL1-RR024153, UL1-RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780] FX This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254); the National Center for Research Resources General Clinical Research Centers Program (grant numbers M01-RR00036 [Washington University School of Medicine], M01-RR00043-45 [Children's Hospital Los Angeles], M01-RR00069 [University of Colorado Denver], M01-RR00084 [Children's Hospital of Pittsburgh], M01-RR01066 [Massachusetts General Hospital], M01-RR00125 [Yale University], and M01-RR14467 [University of Oklahoma Health Sciences Center]); and the National Center for Research Resources Clinical and Translational Science Awards (grant numbers UL1-RR024134 [Children's Hospital of Philadelphia], UL1-RR024139 [Yale University], UL1-RR024153 [Children's Hospital of Pittsburgh], UL1-RR024989 [Case Western Reserve University], UL1-RR024992 [Washington University in St. Louis], UL1-RR025758 [Massachusetts General Hospital], and UL1-RR025780 [University of Colorado Denver]). NR 13 TC 26 Z9 26 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2013 VL 36 IS 6 BP 1772 EP 1774 DI 10.2337/dc12-2387 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UJ UT WOS:000321472600052 ER PT J AU Griffith, JW Luster, AD AF Griffith, Jason W. Luster, Andrew D. TI Targeting cells in motion: Migrating toward improved therapies SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID RELAPSING MULTIPLE-SCLEROSIS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ALPHA-4 INTEGRIN EXPRESSION; NOVO RENAL-TRANSPLANTATION; CXC CHEMOKINE RECEPTOR-5; PLACEBO-CONTROLLED TRIAL; T-CELLS; SPHINGOSINE 1-PHOSPHATE; LYMPHOCYTE RECIRCULATION; DIFFERENTIALLY AFFECTS AB The development of clinical therapeutics that interfere with the migration of leukocytes has revolutionized the treatment of multiple sclerosis and holds great promise for the treatment of a wide range of inflammatory diseases. As the molecules essential for the multi-step adhesion cascade that mediates cellular migration have been elucidated, the number of potential targets available to modulate leukocyte trafficking has increased exponentially. In this Viewpoint, we briefly review our current understanding of these molecular targets and how these targets vary by tissue and leukocyte subset with emphasis on T cells. We then describe the two currently approved therapeutics that target cell migration, natalizumab and fingolimod, and discuss how an improved understanding of their function could pave the way for the development of safer and more efficacious therapies for inflammatory and autoimmune diseases. C1 [Griffith, Jason W.; Luster, Andrew D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Griffith, Jason W.; Luster, Andrew D.] Harvard Univ, Sch Med, Boston, MA USA. [Griffith, Jason W.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Luster, Andrew D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM aluster@mgh.harvard.edu FU NHLBI/NIH T32 training grant; NIAID; NCI at the NIH FX J.W.G. was supported by an NHLBI/NIH T32 training grant and A. D. L. was supported by grants from the NIAID and the NCI at the NIH. NR 75 TC 16 Z9 16 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 2013 VL 43 IS 6 BP 1430 EP 1435 DI 10.1002/eji.201243183 PG 6 WC Immunology SC Immunology GA 169MZ UT WOS:000320785700009 PM 23580465 ER PT J AU Ruiz-Riol, M Mothe, B Gandhi, RT Bhardwaj, N Scadden, DT Sanchez-Merino, V Brander, C AF Ruiz-Riol, Marta Mothe, Beatriz Gandhi, Rajesh T. Bhardwaj, Nina Scadden, David T. Sanchez-Merino, Victor Brander, Christian TI Influenza, but not HIV-specific CTL epitopes, elicits delayed-type hypersensitivity (DTH) reactions in HIV-infected patients SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Delayed-type hypersensitivity; Epitope-specific CTL; HIV infection; Homing markers ID CD8(+) T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN; SKIN-ASSOCIATED LYMPHOCYTES; ATOPIC-DERMATITIS; HOMING RECEPTOR; MEMORY CD4(+); EXPRESSION; VIRUS; RESPONSES; DISEASE AB The induction of cytotoxic T lymphocytes (CTLs) is believed to be an important defense mechanism against viral infections. The availability of simple, sensitive, specific and physiologically informative in vivo tests, applicable to humans, would greatly elucidate the nature of protective immune responses and facilitate immune monitoring in large vaccine trials. Here we studied the possibility of using defined HLA-A*02:01-restricted CTL epitopes from influenza matrix protein (GL9, GILGFVFTL) and HIV Gag p17 (SL9, SLYNTVATL) to elicit a cutaneous delayed-type hypersensitivity (DTH) reaction. Our results show that the GL9 but not the SL9 epitope was able to induce a DTH reaction. HIV infection status, HIV RNA level and CD4(+) T-cell counts were not predictive of the extent of DTH reactions. However, a markedly reduced expression of skin homing markers CD103 and cutaneous lymphocyte associated Ag (CLA) on epitope-specific CTL populations was associated with a lack of SL9 DTH reactivity. These data demonstrate that DTH reactions can be elicited by optimally defined CTL epitopes per se and point towards specific homing markers that are required for such reactions. These data may offer new insights into the immune pathogenesis of HIV infection and provide the basis of novel immune monitoring approaches for large-scale HIV vaccine trials. C1 [Ruiz-Riol, Marta; Mothe, Beatriz; Brander, Christian] HIVACAT, IrsiCaixa AIDS Res Inst, Barcelona, Spain. [Mothe, Beatriz] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Lluita Sida Fdn, E-08193 Barcelona, Spain. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Hematol Malignancies MGH Canc Ctr, Boston, MA 02114 USA. [Bhardwaj, Nina] NYU, Sch Med, Dept Med Pathol & Dermatol, New York, NY USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Sanchez-Merino, Victor] Hosp Clin Barcelona, Serv Immunol, Barcelona, Spain. [Sanchez-Merino, Victor] Hosp Clin Barcelona, IDIBAPS, AIDS Res Grp, HIVACAT, Barcelona, Spain. [Brander, Christian] ICREA, Barcelona, Spain. RP Brander, C (reprint author), Hosp Badalona Germans Trias & Pujol, Lab Retrovirol, Irsicaixa AIDS Res Inst, Ctra Canyet S-N, Barcelona 08916, Spain. EM cbrander@irsicaixa.es OI Brander, Christian/0000-0002-0548-5778 FU amfAR (American Foundation for AIDS Research) [02741-30-RGT] FX This work was funded by a grant from amfAR (American Foundation for AIDS Research, Grant 02741-30-RGT). We thank Lea Henry for excellent technical support and Alysse Wurzel, Walter Howard and Paula O'Connor for help with patient recruitment and follow-up. NR 41 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 2013 VL 43 IS 6 BP 1545 EP 1554 DI 10.1002/eji.201242732 PG 10 WC Immunology SC Immunology GA 169MZ UT WOS:000320785700022 PM 23504637 ER PT J AU Choi, NC Chun, TT Niemierko, A Ancukiewicz, M Fidias, PM Kradin, RL Mathisen, DJ Lynch, TJ Fischman, AJ AF Choi, Noah C. Chun, Tristen T. Niemierko, Andrzej Ancukiewicz, Marek Fidias, Panos M. Kradin, Richard L. Mathisen, Douglas J. Lynch, Thomas J. Fischman, Alan J. TI Potential of F-18-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE F-FDG PET; Personalized radiotherapy; Individualized therapy; Lung cancer; Chemoradiotherapy ID RADIATION-DOSE ESCALATION; FDG-PET; TUMOR-CONTROL; SOLID TUMORS; CHEMOTHERAPY; THERAPY; PROBABILITY; CISPLATIN; SURVIVAL; CRITERIA AB Purpose We investigated the metabolic response of lung cancer to radiotherapy or chemoradiotherapy by F-18-FDG PET and its utility in guiding timely supplementary therapy. Methods Glucose metabolic rate (MRglc) was measured in primary lung cancers during the 3 weeks before, and 10-12 days (S2), 3 months (S3), 6 months (S4), and 12 months (S5) after radiotherapy or chemoradiotherapy. The association between the lowest residual MRglc representing the maximum metabolic response (MRglc-MMR) and tumor control probability (TCP) at 12 months was modeled using logistic regression. Results We accrued 106 patients, of whom 61 completed the serial F-18-FDG PET scans. The median values of MRglc at S2, S3 and S4 determined using a simplified kinetic method (SKM) were, respectively, 0.05, 0.06 and 0.07 mu mol/min/g for tumors with local control and 0.12, 0.16 and 0.19 mu mol/min/g for tumors with local failure, and the maximum standard uptake values (SUVmax) were 1.16, 1.33 and 1.45 for tumors with local control and 2.74, 2.74 and 4.07 for tumors with local failure (p<0.0001). MRglc-MMR was realized at S2 (MRglc-S2) and the values corresponding to TCP 95 %, 90 % and 50 % were 0.036, 0.050 and 0.134 mu mol/min/g using the SKM and 0.70, 0.91 and 1.95 using SUVmax, respectively. Probability cut-off values were generated for a given level of MRglc-S2 based on its predicted TCP, sensitivity and specificity, and MRglc <= 0.071 mu mol/min/g and SUVmax <= 1.45 were determined as the optimum cut-off values for predicted TCP 80 %, sensitivity 100 % and specificity 63 %. Conclusion The cut-off values (MRglc <= 0.071 mu mol/min/g using the SKM and SUVmax <= 1.45) need to be tested for their utility in identifying patients with a high risk of residual cancer after standard dose radiotherapy or chemoradiotherapy and in guiding a timely supplementary dose of radiation or other means of salvage therapy. C1 [Choi, Noah C.; Chun, Tristen T.; Niemierko, Andrzej; Ancukiewicz, Marek] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Fidias, Panos M.; Lynch, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Kradin, Richard L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Mathisen, Douglas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Choi, NC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM nchoi@partners.org FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health [R01 EB002907] FX This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health (grant number R01 EB002907). NR 28 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JUN PY 2013 VL 40 IS 6 BP 832 EP 841 DI 10.1007/s00259-013-2348-4 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 179KO UT WOS:000321519400003 PM 23400506 ER PT J AU Treon, SP AF Treon, Steven P. TI Waldenstrom's macroglobulinaemia: an indolent B-cell lymphoma with distinct molecular and clinical features SO HEMATOLOGICAL ONCOLOGY LA English DT Article DE Waldenstrom's macroglobulinemia; MYD88; hyperviscosity; neuropathy; cryoglobulins; hepcidin ID COLD-REACTING AUTOANTIBODIES; IGM MONOCLONAL GAMMOPATHY; PERIPHERAL NEUROPATHY; SOMATIC MUTATION; ANTIBODY-ACTIVITY; BIOLOGIC ACTIVITY; 6Q DELETION; GENE; IMMUNOGLOBULINS; PARAPROTEINEMIA C1 [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Mayer 548,44 Binney St, Boston, MA 02215 USA. EM Steven_Treon@dfci.harvard.edu NR 59 TC 3 Z9 3 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD JUN PY 2013 VL 31 SU 1 SI SI BP 76 EP 80 DI 10.1002/hon.2071 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 165GX UT WOS:000320472600013 PM 23775655 ER PT J AU Fukuta, Y Doi, Y Muder, RR Agha, ME Hensler, AM Wagener, MM Clarke, LG AF Fukuta, Y. Doi, Y. Muder, R. R. Agha, M. E. Hensler, A. M. Wagener, M. M. Clarke, L. G. TI Risk factors for acquisition of multi-drug resistant Acinetobacter baumannii among cancer patients SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Meeting Abstract CT 28th International Congress of Chemotherapy and Infection Incorporating / 14th Asia-Pacific Congress of Clinical Microbiology and Infection CY JUN 05-08, 2013 CL Yokohama, JAPAN SP Int Soc Chemotherapy C1 [Fukuta, Y.; Doi, Y.; Clarke, L. G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Muder, R. R.] VA Pittsburgh Healthcare Syst, Infect Control, Pittsburgh, PA USA. [Agha, M. E.] Univ Pittsburgh, Med Ctr, Hilman Canc Ctr, Pittsburgh, PA USA. [Hensler, A. M.] Univ Pittsburgh, Med Ctr Shadyside, Pittsburgh, PA USA. [Wagener, M. M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. EM nana-yuri@hotmail.co.jp 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 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUN PY 2013 VL 42 SU 2 BP S140 EP S141 PG 2 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 178KS UT WOS:000321447400436 ER PT J AU Neilan, TG Coelho, OR Shah, RV Abbasi, SA Heydari, B Watanabe, E Chen, YC Mandry, D Pierre-Mongeon, F Blankstein, R Kwong, RY Jerosch-Herold, M AF Neilan, Tomas G. Coelho-Filho, Otavio R. Shah, Ravi V. Abbasi, Siddique A. Heydari, Bobak Watanabe, Eri Chen, Yucheng Mandry, Damien Pierre-Mongeon, Francois Blankstein, Ron Kwong, Raymond Y. Jerosch-Herold, Michael TI Myocardial Extracellular Volume Fraction From T1 Measurements in Healthy Volunteers and Mice Relationship to Aging and Cardiac Dimensions SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; extracellular matrix; myocardial fibrosis; T1 measurements ID CARDIOVASCULAR MAGNETIC-RESONANCE; DIASTOLIC HEART-FAILURE; HYPERTROPHIC CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; PARTITION-COEFFICIENT; GD-DTPA; GADOPENTETATE DIMEGLUMINE; BLOOD-FLOW; FIBROSIS; INFARCTION AB OBJECTIVES This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers. BACKGROUND Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. METHODS Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis. RESULTS In healthy volunteers (N = 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 +/- 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r = 0.74, p < 0.001), maximal left atrial volume index.(r = 0.67, p < 0.001), and indexed left ventricular mass. There were no differences in the ECV between segments in a slice or between slices. In mice (N = 12), the myocardial ECV ranged from 0.20 to 0.32 and increased with age (0.22 +/- 0.02 vs. 0.30 +/- 0.02, juvenile vs. aged mice, p < 0.001). In mice, the ECV correlated with the extent of myocardial fibrosis (r = 0.94, p < 0.001). CONCLUSIONS In healthy volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis. (c) 2013 by the American College of Cardiology Foundation C1 [Neilan, Tomas G.; Coelho-Filho, Otavio R.; Shah, Ravi V.; Abbasi, Siddique A.; Heydari, Bobak; Chen, Yucheng; Mandry, Damien; Pierre-Mongeon, Francois; Blankstein, Ron; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Neilan, Tomas G.; Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Coelho-Filho, Otavio R.] Univ Estadual Campinas, UNICAMP, Sch Med Sci, Div Cardiol, Sao Paulo, Brazil. [Watanabe, Eri; Jerosch-Herold, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Radiol, Boston, MA 02115 USA. [Pierre-Mongeon, Francois] Univ Montreal, Montreal Heart Inst, Dept Med, Div Noninvas Cardiol, Montreal, PQ, Canada. RP Jerosch-Herold, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mjerosch-herold@bics.bwh.harvard.edu OI Abbasi, Siddique/0000-0002-9601-7565 FU American Heart Association Fellow [12FTF12060588]; NIH T32 Training Grant [T32HL09430101A1]; Montreal Heart Institute Foundation, Montreal, Canada; National Institutes of Health [R01HL091157, R01HL090634-01A1] FX From *Noninvasive Cardiovascular Imaging, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; dagger Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; double dagger Cardiology Division, School of Medical Science, State University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil; Division of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and the parallel to Division of Noninvasive Cardiology, Department of Medicine, Montreal Heart Institute, Universite de Montreal, Montreal, Quebec, Canada. Dr. Neilan is supported by an American Heart Association Fellow to Faculty grant (12FTF12060588) and previously by an NIH T32 Training Grant (T32HL09430101A1). Dr. Mongeon receives financial support for research from the Montreal Heart Institute Foundation, Montreal, Canada. Dr. Kwong receives salary support from a research grant from the National Institutes of Health (R01HL091157). Dr. Jerosch-Herold is supported in part by a research grant from the National Institutes of Health (R01HL090634-01A1); and is listed as co-inventor on a pending patent application related to detection of diffuse fibrosis by MRI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Neilan and Coelho-Filho contributed equally to this work. NR 41 TC 23 Z9 24 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUN PY 2013 VL 6 IS 6 BP 672 EP 683 DI 10.1016/j.jcmg.2012.09.020 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 172CI UT WOS:000320977200006 PM 23643283 ER PT J AU Pearson, DA Santos, CW Aman, MG Arnold, LE Casat, CD Mansour, R Lane, DM Loveland, KA Bukstein, OG Jerger, SW Factor, P Vanwoerden, S Perez, E Cleveland, LA AF Pearson, Deborah A. Santos, Cynthia W. Aman, Michael G. Arnold, L. Eugene Casat, Charles D. Mansour, Rosleen Lane, David M. Loveland, Katherine A. Bukstein, Oscar G. Jerger, Susan W. Factor, Perry Vanwoerden, Salome Perez, Evelyn Cleveland, Lynne A. TI Effects of Extended Release Methylphenidate Treatment on Ratings of Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Behavior in Children with Autism Spectrum Disorders and ADHD Symptoms SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; EARLY INFANTILE-AUTISM; STIMULANT MEDICATION; MENTAL-RETARDATION; PSYCHIATRIC-DISORDERS; FOLLOW-UP; TRIAL; PHARMACOTHERAPY; PREVALENCE AB Objective: The purpose of this study was to examine the behavioral effects of four doses of psychostimulant medication, combining extended-release methylphenidate (MPH) in the morning with immediate-release MPH in the afternoon. Method: The sample comprised 24 children (19 boys; 5 girls) who met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age = 8.8 years, SD = 1.7; mean intelligence quotient [IQ] = 85; SD = 16.8). Effects of four dose levels of MPH on parent and teacher behavioral ratings were investigated using a within-subject, crossover, placebo-controlled design. Results: MPH treatment was associated with significant declines in hyperactive and impulsive behavior at both home and school. Parents noted significant declines in inattentive and oppositional behavior, and improvements in social skills. No exacerbation of stereotypies was noted, and side effects were similar to those seen in typically developing children with ADHD. Dose response was primarily linear in the dose range studied. Conclusions: The results of this study suggest that MPH formulations are efficacious and well-tolerated for children with ASD and significant ADHD symptoms. C1 [Pearson, Deborah A.; Santos, Cynthia W.; Mansour, Rosleen; Loveland, Katherine A.; Bukstein, Oscar G.; Factor, Perry; Vanwoerden, Salome; Perez, Evelyn; Cleveland, Lynne A.] Univ Texas Houston, Sch Med, Houston, TX 77054 USA. [Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Casat, Charles D.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lane, David M.] Rice Univ, Dept Psychol, Houston, TX 77251 USA. [Jerger, Susan W.] Univ Texas Dallas, Sch Behav & Brain Sci, Dallas, TX 75230 USA. RP Pearson, DA (reprint author), Univ Texas Houston, Sch Med, Dept Psychiat & Behav Sci, 1941 East Rd, Houston, TX 77054 USA. EM Deborah.A.Pearson@uth.tmc.edu FU National Institute of Mental Health (NIMH) [MH072263] FX This study was funded by grant number MH072263 from the National Institute of Mental Health (NIMH). NR 73 TC 9 Z9 11 U1 1 U2 32 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD JUN PY 2013 VL 23 IS 5 BP 337 EP 351 DI 10.1089/cap.2012.0096 PG 15 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 168LJ UT WOS:000320707000006 PM 23782128 ER PT J AU Joshi, G Biederman, J Petty, C Goldin, RL Furtak, SL Wozniak, J AF Joshi, Gagan Biederman, Joseph Petty, Carter Goldin, Rachel L. Furtak, Stephannie L. Wozniak, Janet TI Examining the Comorbidity of Bipolar Disorder and Autism Spectrum Disorders: A Large Controlled Analysis of Phenotypic and Familial Correlates in a Referred Population of Youth With Bipolar I Disorder With and Without Autism Spectrum Disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHIATRIC CO-MORBIDITY; CONDUCT DISORDER; ONSET MANIA; CHILDREN; ADOLESCENTS; INTERVIEW; CHILDHOOD; DIAGNOSIS; TRAITS; SCALE AB Objective: Although mood dysregulation is frequently associated with autism spectrum disorders (ASD) and autistic traits are common in youth with bipolar disorder, uncertainties remain regarding the comorbid occurrence of bipolar disorder and ASD. This study examines the clinical and familial correlates of bipolar disorder when it occurs with and without ASD comorbidity in a well-characterized, research-referred population of youth with bipolar disorder. We hypothesized that in youth with bipolar disorder, the clinical and familial correlates of bipolar disorder will be comparable irrespective of the comorbidity with ASD. Method: Clinical correlates and familial risk were assessed by secondary analysis of the data from a large family study of youth with bipolar I disorder (diagnosis based on DSM-IV criteria; probands n=157, relatives n=487; study period: November 1997-September 2002). Findings in bipolar I youth were compared with those in youth with attention-deficit/hyperactivity disorder (diagnosis based on DSM-III-R criteria) without bipolar I disorder (probands n=162, relatives n=511) and age- and sex-matched controls without bipolar I disorder or attention-deficit/hyperactivity disorder (probands n=136, relatives n=411). All subjects were comprehensively assessed using structured diagnostic interviews and a wide range of nonoverlapping measures assessing multiple dimensions of functioning. Results: Thirty percent (47/155) of the bipolar I probands met criteria for ASD (diagnosis based on DSM-III-R criteria). The mean +/- SD age at onset of bipolar I disorder was significantly earlier in the presence of ASD comorbidity (4.7 +/- 2.9 vs 6.3 +/- 3.7 years; P=.01).The phenotypic and familial correlates of bipolar disorder were similar in youth with and without ASD comorbidity. Conclusions: A clinically significant minority of youth with bipolar I disorder suffers from comorbid ASD. Phenotypic and familial correlates of bipolar disorder were typical of the disorder in the presence of ASD comorbidity. Bipolar I disorder comorbidity with ASD represents a very severe psychopathologic state in youth. C1 [Joshi, Gagan; Biederman, Joseph; Petty, Carter; Goldin, Rachel L.; Furtak, Stephannie L.; Wozniak, Janet] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Joshi, Gagan; Biederman, Joseph; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,YAW 6900, Boston, MA 02114 USA. EM joshi.gagan@mgh.harvard.edu FU Forest and Duke University; Schering-Plough; Shire; ElMindA; US Department of Defense; Johnson Johnson; Eli Lilly; Forest; National Institute of Mental Health (NIMH); Ethel DuPont Warren Fellowship Award; Pilot Research Award from the American Academy of Child and Adolescent Psychiatry; NIMH; McNeil Pediatrics (SynerMed Communications); Bristol-Myers Squibb; GlaxoSmithKline; Pfizer; Merck; Cephalon; McNeil; Abbott; Novartis; Organon; Otsuka; Takeda; New River; Janssen; Next Wave; Fundacion Areces; Medice; Spanish Child Psychiatry Association; Alza; AstraZeneca; Celltech; Esai; Glaxo; Gliatech; National Alliance for Research on Schizophrenia and Depression; National Institute on Drug Abuse, New River; National Institute of Child Health and Human Development; Noven; Neurosearch; Pharmacia; Prechter Foundation; Stanley Foundation; UCB; Wyeth; Merck/Schering-Plough; Zeo; Axon; Boehringer-Ingelheim; Covance; Jazz; King; Luitpold; Neurogen; Novadel; Sanofi-Aventis; Sepracor; Sunovion; UCB (Schwarz); National Institutes of Health [K08MH001503, R01MH066237, R01MH050657, R01HD036317]; Norma Fine Pediatric Psychopharmacology Fellowship Fund; Pediatric Psychopharmacology Council Fund; Heinz C. Prechter Bipolar Research Fund FX Dr Joshi currently receives research support from Forest and Duke University and is a coinvestigator for clinical trials sponsored by Schering-Plough, Shire, ElMindA, and US Department of Defense. In 2011, Dr Joshi received research support from Shire, Johnson & Johnson, Eli Lilly, Forest, Schering-Plough, ElMindA, and National Institute of Mental Health (NIMH). In previous years, Dr Joshi received research support from the following sources: Ethel DuPont Warren Fellowship Award (2005-2006), Pilot Research Award from the American Academy of Child and Adolescent Psychiatry (2005), NIMH (reviewer and member of the NIMH Editorial Board), McNeil Pediatrics (CME sponsored by SynerMed Communications), Bristol-Myers Squibb (site principal investigator [PI] for multicenter trial); and GlaxoSmithKline (site PI for multicenter trial); Shire (member of national advisory board) and was a subinvestigator for clinical trials sponsored by Shire, Johnson & Johnson, Pfizer, Merck, Cephalon, McNeil, Eli Lilly, Abbott, Novartis, Bristol-Myers Squibb, Organon, Otsuka, Takeda, and New River. Dr Biederman currently receives research support from ElMindA, Janssen, McNeil, Next Wave, and Shire. In 2011, Dr Biederman gave a single unpaid talk for Juste Pharmaceutical Spain and received honoraria from MGH Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. In 2010, Dr Biederman received a speaker's fee from Fundacion Dr. Manuel Camelo AC, provided single consultations for Shionogi and Cipher, and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr Biederman received speaker's fees from Fundacion Areces, Medice, and the Spanish Child Psychiatry Association. In previous years, Dr Biederman received research support, consultation fees, or speaker's fees from Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, National Alliance for Research on Schizophrenia and Depression, National Institute on Drug Abuse, New River, National Institute of Child Health and Human Development, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Prechter Foundation, Shire, Stanley Foundation, UCB, and Wyeth. In 2011-2012, Dr Wozniak received research support from Merck/Schering-Plough, McNeil, and Shire. In the past, she has received research support, consultation fees, or speaker's fees from Eli Lilly, Janssen, Johnson & Johnson, McNeil, Pfizer, and Shire. She is the author of the book Is Your Child Bipolar? published May 2008, Bantam Books. In 2011-2012, her spouse, John Winkelman, MD, PhD, received consultation fees from Pfizer, UCB, Zeo, and Sunovion for his role as consultant. He received research support from GlaxoSmithKline for his role as research study staff In the past, he has received research support, consultation fees, or speaker's fees from Axon, Boehringer-Ingelheim, Covance, Cephalon, Eli Lilly, GlaxoSmithKline, Impax, Jazz, King, Luitpold, Novartis, Neurogen, Novadel, Pfizer, Sanofi-Aventis, Sepracor, Sunovion, Takeda, UCB (Schwarz), Wyeth, and Zeo. Mr Petty and Mss Goldin and Furtak have no conflicts of interest to report.; This work was supported by National Institutes of Health grants K08MH001503 and R01MH066237 to Dr Wozniak and R01MH050657 and R01HD036317 to Dr Biederman. This work was also funded in part by the Norma Fine Pediatric Psychopharmacology Fellowship Fund, the Pediatric Psychopharmacology Council Fund, and the Heinz C. Prechter Bipolar Research Fund. NR 41 TC 18 Z9 18 U1 4 U2 27 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2013 VL 74 IS 6 BP 578 EP 586 DI 10.4088/JCP.12m07392 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 176QJ UT WOS:000321318900002 PM 23842009 ER PT J AU McHugh, RK Whitton, SW Peckham, AD Welge, JA Otto, MW AF McHugh, R. Kathryn Whitton, Sarah W. Peckham, Andrew D. Welge, Jeffrey A. Otto, Michael W. TI Patient Preference for Psychological vs Pharmacologic Treatment of Psychiatric Disorders: A Meta-Analytic Review SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID COGNITIVE-BEHAVIORAL THERAPY; DEPRESSION TREATMENT PREFERENCES; PRIMARY-CARE PATIENTS; RANDOMIZED-CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSION; PANIC DISORDER; COST-EFFECTIVENESS AB Objective: Evidence-based practice involves the consideration of efficacy and effectiveness, clinical expertise, and patient preference in treatment selection. However, patient preference for psychiatric treatment has been understudied, The aim of this meta-analytic review was to provide an estimate of the proportion of patients preferring psychological treatment relative to medication for psychiatric disorders. Data Sources: A literature search was conducted using PubMed, PsycINFO, and the Cochrane Collaboration library through August 2011 for studies written in English that assessed adult patient preferences for the treatment of psychiatric disorders. The following search terms and subject headings were used in combination: patient preference, consumer preference, therapeutics, psychotherapy, drug therapy, mental disorders, depression, anxiety, insomnia, bipolar disorder, schizophrenia, substance-related disorder, eating disorder, and personality disorder. In addition, the reference sections of identified articles were examined to locate any additional articles not captured by this search. Study Selection: Studies that assessed preferred type of treatment and included at least 1 psychological treatment and 1 pharmacologic treatment were included. Of the 644 articles identified, 34 met criteria for inclusion. Data Extraction: Authors extracted relevant data including the proportion of participants reporting preference for psychological or pharmacologic treatment. Results:The proportion of adult patients preferring psychological treatment was 0.75 (95% Cl, 0.69-0.80), which was significantly higher than equivalent preference (ie, higher than 0.50; P<.001). Sensitivity analyses suggested that younger patients (P=.05) and women (P<.01) were significantly more likely to choose psychological treatment. A preference for psychological treatment was consistently evident in both treatment-seeking and unselected (ie, non-treatment-seeking) samples (P<.001 for both) but was somewhat stronger for unselected samples. Conclusions: Aggregation of patient preferences across diverse settings yielded a significant 3-fold preference for psychological treatment. Given evidence for enhanced outcomes among those receiving their preferred psychiatric treatment and the trends for decreasing utilization of psychotherapy, strategies to maximize the linkage of patients to preferred care are needed. C1 [McHugh, R. Kathryn] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02478 USA. [McHugh, R. Kathryn] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Whitton, Sarah W.] Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA. [Peckham, Andrew D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Welge, Jeffrey A.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP McHugh, RK (reprint author), McLean Hosp, Proctor House 3 MS 222,115 Mill St, Belmont, MA 02478 USA. EM kmchugh@mclean.harvard.edu OI McHugh, R. Kathryn/0000-0002-3011-8697 FU National Institutes of Health Institutional Clinical and Translational Science Award [5ULIRR026314-02]; National Institute of Mental Health Excellence in Training Award [R25 MH08478]; Oxford University Press; Routledge; Springer; National Institute of Mental Health FX Dr Otto has been a consultant for MicroTransponder and has received book royalties from Oxford University Press, Routledge, and Springer. Drs McHugh, Whitton, and Welge and Mr Peckham have no conflicts of interest to report.; Supported in part by National Institutes of Health Institutional Clinical and Translational Science Award 5ULIRR026314-02 (Drs Whitton and Welge) and by National Institute of Mental Health Excellence in Training Award R25 MH08478 (Dr Otto).; The National Institutes of Health had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication. The National Institute of Mental Health had no role other than financial support. NR 68 TC 86 Z9 87 U1 5 U2 65 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2013 VL 74 IS 6 BP 595 EP 602 DI 10.4088/JCP.12r07757 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 176QJ UT WOS:000321318900004 PM 23842011 ER PT J AU Herr, MW Gray, ST Erman, AB Curry, WT Deschler, DG Lin, DT AF Herr, Marc W. Gray, Stacey T. Erman, Audrey B. Curry, William T. Deschler, Daniel G. Lin, Derrick T. TI Orbital Preservation in Patients with Esthesioneuroblastoma SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE esthesioneuro-blastoma; anterior craniofacial resection; orbital preservation; skull base ID OLFACTORY NEUROBLASTOMA; SURGICAL-MANAGEMENT; PARANASAL SINUSES; EXPERIENCE; EYE; CHEMOTHERAPY; RADIATION; NEOPLASMS; RESECTION; SURGERY AB Objectives Surgical resection in addition to adjuvant radiation with or without chemotherapy is the mainstay of treatment for esthesioneuroblastoma (ENB). However, management of patients with orbital involvement remains controversial. Historically, orbital exenteration has been advocated when there is evidence of periorbital invasion. Recently, the indications for orbital exenteration have become more selective and orbital preservation has been advocated. We report our experience with anterior craniofacial resection and orbital preservation in patients with ENB. Design Retrospective review of all patients diagnosed with esthesioneuroblastoma who underwent traditional open anterior craniofacial resection at the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary Cranial Base Center from 1997 to 2008. Results Sixteen patients were identified with a mean follow-up of 76 months. All patients underwent anterior craniofacial resection via an open approach and adjuvant proton beam radiation. Six of the 16 patients had evidence of either periorbital or lacrimal sac involvement at the time of surgery. All of these patients underwent periorbital resection to negative histologic margins with preservation of the orbit. Conclusion In our study, patients with ENB and periorbital invasion-who were treated with anterior craniofacial resection and periorbital resection with orbital preservation-had no evidence of decreased survival. In all patients, negative histologic margins of the periorbital resection were achieved. C1 [Herr, Marc W.; Gray, Stacey T.; Deschler, Daniel G.; Lin, Derrick T.] Massachusetts Gen Hosp, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Cranial Base Ctr, Boston, MA 02114 USA. [Erman, Audrey B.] Univ Arizona, Dept Otolaryngol Head & Neck Surg, Ctr Canc, Tucson, AZ USA. [Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Herr, MW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM marc_herr@meei.harvard.edu NR 17 TC 2 Z9 2 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD JUN PY 2013 VL 74 IS 3 BP 142 EP 145 DI 10.1055/s-0033-1338259 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 175ZQ UT WOS:000321272900007 PM 24436904 ER PT J AU Rosenberg, SM Partridge, AH AF Rosenberg, Shoshana M. Partridge, Ann H. TI Premature menopause in young breast cancer: effects on quality of life and treatment interventions SO JOURNAL OF THORACIC DISEASE LA English DT Review DE Premature menopause; young women; breast cancer; quality of life (QOL) ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; HOT FLASHES; ADJUVANT CHEMOTHERAPY; OVARIAN FAILURE; PHYSICAL-ACTIVITY; VASOMOTOR SYMPTOMS; BODY-COMPOSITION; SEXUAL PROBLEMS; BLACK COHOSH AB Many young women are at increased risk for premature menopause following adjuvant treatment for breast cancer. These women must deal with consequences of menopause, including loss of fertility and physiologic symptoms such as night sweats, hot flashes, vaginal dryness, and weight gain. These symptoms can be particularly distressing for young women and can adversely affect both health-related and psychosocial quality of life (QOL). While there are a wide range of pharmacologic and non-pharmacologic interventions available to help with these symptoms and in turn, improve QOL, there is little data available about the use and efficacy of these interventions in younger women who become menopausal as a result of their breast cancer treatment. Future studies should focus on this vulnerable population, with the goal of identifying effective strategies to relieve symptoms and improve quality of life in young breast cancer survivors. C1 [Rosenberg, Shoshana M.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Rosenberg, Shoshana M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenberg, SM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW601, Boston, MA 02215 USA. EM shoshana_rosenberg@dfci.harvard.edu FU NIH [5 R25 CA057711] FX Dr. Rosenberg is funded by NIH 5 R25 CA057711. NR 72 TC 14 Z9 14 U1 1 U2 7 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 JUN PY 2013 VL 5 SU 1 BP S55 EP S61 DI 10.3978/j.issn.2072-1439.2013.06.20 PG 7 WC Respiratory System SC Respiratory System GA 182ME UT WOS:000321746200008 PM 23819028 ER PT J AU Ryan, J Letai, A AF Ryan, Jeremy Letai, Anthony TI BH3 profiling in whole cells by fluorimeter or FACS SO METHODS LA English DT Article DE Mitochondria; Apoptosis; BCL-2; Flow Cytometry; Cancer; Chemotherapy ID REVERSIBLE MEMBRANE PERMEABILIZATION; STREPTOLYSIN-O; CYTOCHROME-C; MITOCHONDRIA; APOPTOSIS; PROTEINS; DEATH; SIGNALS AB Rapid analysis of a cell's propensity to undergo apoptosis through the mitochondrial pathway is hindered by the complex network of interactions between more than fifteen known members of the BCL2 family that govern the decision to undergo mitochondrial apoptosis, and measurement of protein levels alone fails to account for critical interactions between the proteins. To address this issue, we have developed two functional assays for same-day analysis of cell lines or primary tissue samples. Using defined inputs in the form of peptides derived primarily from the BH3 domains of pro-apoptotic members of the BCL2 family, we invoke a response in the mitochondria in the form of mitochondrial outer membrane permeabilization measured indirectly using potential sensitive dyes. BH3 profiling can be applied to any viable single cell suspension and provides a response from the sum total of all known and unknown interactions within the BCL2 family for each stimulus, and the pattern of response can provide both a cell's propensity towards mitochondrial apoptosis, or 'priming', as well as indicate dependencies on specific anti-apoptotic proteins. Described here are optimized conditions for both plate-based and FACS-based BH3 profiling for homogeneous and heterogeneous samples. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ryan, Jeremy; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Letai, Anthony] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Letai, A (reprint author), 450 Brookline Ave,Mayer 429, Boston, MA 02215 USA. EM Anthony_Letai@dfci.harvard.edu FU NIH [F31 CA150562, P01 CA139980, R01 CA129974] FX The authors gratefully acknowledge support from the following sources: NIH grants F31 CA150562, P01 CA139980, and R01 CA129974. A.L. is a Leukemia and Lymphoma Society Scholar. A.L. was a cofounder and formerly served on the scientific advisory board of Eutropics Pharmaceuticals, which has a license for BH3 profiling. NR 28 TC 32 Z9 32 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JUN 1 PY 2013 VL 61 IS 2 BP 156 EP 164 DI 10.1016/j.ymeth.2013.04.006 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175ML UT WOS:000321234700010 PM 23607990 ER PT J AU Peters, MAK Thompson, B Merabet, LB Wu, AD Shams, L AF Peters, Megan A. K. Thompson, Benjamin Merabet, Lotfi B. Wu, Allan D. Shams, Ladan TI Anodal tDCS to V1 blocks visual perceptual learning consolidation SO NEUROPSYCHOLOGIA LA English DT Article DE Transcranial direct current stimulation; Visual perception; Perceptual learning; External modulation of visual cortex; Contrast enhancement; Consolidation; Visual learning; Anodal tDCS ID DIRECT-CURRENT STIMULATION; HUMAN MOTOR CORTEX; EXCITABILITY CHANGES; ELECTROPHYSIOLOGICAL EVIDENCE; PHOSPHENE THRESHOLDS; MODULATION; HUMANS; IMPLICIT; NOISE AB This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Peters, Megan A. K.; Shams, Ladan] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Thompson, Benjamin] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand. [Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Vis Rehabil Ctr,Dept Ophthalmol, Boston, MA USA. [Wu, Allan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Shams, Ladan] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. RP Peters, MAK (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall, Los Angeles, CA 90095 USA. EM meganakpeters@ucla.edu; b.thompson@auckland.ac.nz; lotfi_merabet@meei.harvard.edu; allanwu@mednet.ucla.edu; lshams@psych.ucla.edu FU NSF [1057969]; Marsden Fund of New Zealand FX We thank Felipe Fregni for helpful discussions. MP was supported by an NSF graduate research fellowship. BT was supported by the Marsden Fund of New Zealand. LS was supported by NSF Grant 1057969. NR 35 TC 23 Z9 24 U1 2 U2 18 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 JUN PY 2013 VL 51 IS 7 BP 1234 EP 1239 DI 10.1016/j.neuropsychologia.2013.03.013 PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 179RQ UT WOS:000321539400011 PM 23562964 ER PT J AU Bernardino, I Castelhano, J Farivar, R Silva, ED Castelo-Branco, M AF Bernardino, Ines Castelhano, Joao Farivar, Reza Silva, Eduardo D. Castelo-Branco, Miguel TI Neural correlates of visual integration in Williams syndrome: Gamma oscillation patterns in a model of impaired coherence SO NEUROPSYCHOLOGIA LA English DT Article DE Williams syndrome; Low-gamma oscillations; 3D integration; Visual coherence; EEG/ERP ID DORSAL-STREAM; BAND ACTIVITY; FROM-MOTION; BRAIN; COGNITION; SYNCHRONIZATION; PERCEPTION; DISORDERS; ATTENTION; CHILDREN AB Williams syndrome (WS) is a clinical model of dorsal stream vulnerability and impaired visual integration. However, little is still known about the neurophysiological correlates of perceptual integration in this condition. We have used a 3D structure-from-motion (SFM) integrative task to characterize the neuronal underpinnings of 3D perception in WS and to probe whether gamma oscillatory patterns reflect changed holistic perception. Coherent faces were parametrically modulated in 3D depth (three different depth levels) to vary levels of stimulus ambiguity. We have found that the electrophysiological (EEG/ERP) correlates of such holistic percepts were distinct across groups. Independent component analysis demonstrated the presence of a novel component with a late positivity around 200 ms that was absent in controls. Source localization analysis of ERP signals showed a posterior occipital shift in WS and reduced parietal dorsal stream sources. Interestingly, low gamma-band oscillations (20-40 Hz) induced by this 3D perceptual integration task were significantly stronger and sustained during the stimulus presentation in WS whereas high gamma-band oscillations (60-90 Hz) were reduced in this clinical model of impaired visual coherence, as compared to controls. These observations suggest that dorsal stream processing of 3D SFM stimuli has distinct neural correlates in WS and different cognitive strategies are employed by these patients to reach visual coherence. Importantly, we found evidence for the presence of different sub-bands (20-40 Hz/60-90 Hz) within the gamma range which can be dissociated concerning the respective role On the coherent percept formation, both in typical and atypical development. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Bernardino, Ines; Castelhano, Joao; Silva, Eduardo D.; Castelo-Branco, Miguel] Univ Coimbra, IBILI, Visual Neurosci Lab, Fac Med, P-3000354 Coimbra, Portugal. [Farivar, Reza] Harvard Univ, Sch Med, Charlestown, MA USA. [Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Silva, Eduardo D.] Univ Hosp Coimbra, Dept Ophthalmol, Ctr Hereditary Eye Dis, Coimbra, Portugal. RP Castelo-Branco, M (reprint author), Univ Coimbra, IBILI, Visual Neurosci Lab, Fac Med, Azinhaga Santa Comba, P-3000354 Coimbra, Portugal. EM mcbranco@ibili.uc.pt RI Castelo-Branco, Miguel/E-5689-2010; OI Bernardino, Ines/0000-0003-3123-008X; Silva, Eduardo/0000-0002-2739-9854; Castelhano, Joao/0000-0002-8996-1515; Castelo-Branco, Miguel/0000-0003-4364-6373 FU Portuguese Foundation for Science and Technology [PTDC/SAU-NEU/68483/2006, PTDC/SAU-ORG/118380/2010, COMPETE, PEst-C/SAU/UI3282/2011, PIC/IC/82986/2007]; [SRFH/BD/41401/2007]; [SFRH/BD/65341/2009] FX We are grateful to the participants and their families for their participation and support, and Eugenio Rodriguez for his support in data analysis. This research was supported by the Portuguese Foundation for Science and Technology grant numbers: PTDC/SAU-NEU/68483/2006, PTDC/SAU-ORG/118380/2010, COMPETE, PEst-C/SAU/UI3282/2011 and PIC/IC/82986/2007 to M.C.B. (PI); and individual scholarships-SRFH/BD/41401/2007 to I.B. and SFRH/BD/65341/2009 to J.C. NR 61 TC 5 Z9 5 U1 0 U2 8 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 JUN PY 2013 VL 51 IS 7 BP 1287 EP 1295 DI 10.1016/j.neuropsychologia.2013.03.020 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 179RQ UT WOS:000321539400017 PM 23587664 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI In This Issue: Personalized Medicine SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), 10 N Grove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2013 VL 18 IS 6 BP 639 EP 639 DI 10.1634/theoncologist.2013-0211 PG 1 WC Oncology SC Oncology GA 172YL UT WOS:000321043200001 PM 23814156 ER PT J AU Chabner, BA Ellisen, LW Iafrate, AJ AF Chabner, Bruce A. Ellisen, Leif W. Iafrate, A. John TI Personalized Medicine: Hype or Reality SO ONCOLOGIST LA English DT Editorial Material ID CELL LUNG-CANCER; PHILADELPHIA-CHROMOSOME; THERAPY; MUTATIONS; MELANOMA; BRAF C1 [Chabner, Bruce A.; Ellisen, Leif W.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), 10 N Grove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 21 TC 4 Z9 4 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2013 VL 18 IS 6 BP 640 EP 643 DI 10.1634/theoncologist.2013-0210 PG 4 WC Oncology SC Oncology GA 172YL UT WOS:000321043200002 PM 23814157 ER PT J AU Doroshow, JH Sleijfer, S Stupp, R Anderson, K AF Doroshow, James H. Sleijfer, Stefan Stupp, Roger Anderson, Kenneth TI Cancer Clinical Trials-Do We Need a New Algorithm in the Age of Stratified Medicine? SO ONCOLOGIST LA English DT Editorial Material C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Sleijfer, Stefan] Erasmus Univ, Med Ctr, Inst Canc, Rotterdam, Netherlands. [Sleijfer, Stefan] Netherlands Ctr, Rotterdam, Netherlands. [Stupp, Roger] Univ Lausanne, Dept Clin Neurosci, Lausanne, Switzerland. [Stupp, Roger] Univ Zurich Hosp, Ctr Canc, CH-8091 Zurich, Switzerland. [Stupp, Roger] EORTC, Brussels, Belgium. [Anderson, Kenneth] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Anderson, Kenneth] Dana Farber Canc Inst, Kraft Family Blood Ctr, Boston, MA 02115 USA. RP Doroshow, JH (reprint author), NCI, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov NR 5 TC 4 Z9 4 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2013 VL 18 IS 6 BP 651 EP 652 DI 10.1634/theoncologist.2013-0190 PG 2 WC Oncology SC Oncology GA 172YL UT WOS:000321043200006 PM 23814160 ER PT J AU Lautenschlaeger, T George, A Klimowicz, AC Efstathiou, JA Wu, CL Sandler, H Shipley, WU Tester, WJ Hagan, MP Magliocco, AM Chakravarti, A AF Lautenschlaeger, Tim George, Asha Klimowicz, Alexander C. Efstathiou, Jason A. Wu, Chin-Lee Sandler, Howard Shipley, William U. Tester, William J. Hagan, Michael P. Magliocco, Anthony M. Chakravarti, Arnab TI Bladder Preservation Therapy for Muscle-Invading Bladder Cancers on Radiation Therapy Oncology Group Trials 8802, 8903, 9506, and 9706: Vascular Endothelial Growth Factor B Overexpression Predicts for Increased Distant Metastasis and Shorter Survival SO ONCOLOGIST LA English DT Article AB Background. From 1988 to 1999, the Radiation Therapy Oncology Group (RTOG) conducted four prospective studies (8802, 8903, 9506, 9706) of patients with clinical stage T2-4a muscle-invasive bladder cancer. Treatment was selective bladder preservation using transurethral surgery (TURBT) plus cisplatin-based induction and consolidation chemoradiation regimens, reserving radical cystectomy for invasive tumor recurrence. We investigated vascular endothelial growth factor (VEGF) pathway biomarkers in this unique clinical data-set (median follow-up of 3.1 years). Methods. A total of 43 patients with tissue available from the entry TURBT were included in this analysis. Expression of VEGF ligands and receptors were quantified and scored by the AQUA platform (HistoRX, now Genoptix, Carlsbad, CA) and analyzed after median split. Results. VEGF expression levels were not associated with increased rates of complete response to induction chemoradiation. Higher levels of cytoplasmic VEGF-B, VEGF-C, and VEGF-R2 were associated with decreased overall survival rates. The 3-year overall survival estimates for high and low expressers were 43.7% and 75% for VEGF-B cytoplasm (p = .01), 40.2% and 86.7% for VEGF-C cytoplasm (p = .01), and 49.7% and 66.7% for VEGF-R2 cytoplasm (p = .02). Higher expression levels of cytoplasm VEGF-B were associated with higher rates of distant failure (p = .01). [GRAPHICS] Conclusions. Although VEGF ligands and receptors do not appear to be associated with complete response to induction chemoradiation for muscle- invasive bladder cancer, we report significant associations with overall survival and distant failure for certain VEGF family members. C1 [Lautenschlaeger, Tim; Chakravarti, Arnab] Ohio State Univ, Wexner Med Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA. [George, Asha] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Klimowicz, Alexander C.] Univ Calgary, Translat Res Lab, Funct Tissue Imaging Unit, Calgary, AB, Canada. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Clark Ctr Radiat Oncol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Urol Res Lab, Boston, MA 02114 USA. [Shipley, William U.] Massachusetts Gen Hosp, Genitourinary Oncol Unit, Boston, MA 02114 USA. [Sandler, Howard] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Tester, William J.] Einstein Med Ctr, Div Med Oncol, Philadelphia, PA USA. [Hagan, Michael P.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. [Magliocco, Anthony M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Anat Pathol, Tampa, FL 33682 USA. [Magliocco, Anthony M.] Res Inst, Tampa, FL USA. RP Lautenschlaeger, T (reprint author), Ohio State Univ, Wexner Med Ctr, Arthur G James Comprehens Canc Ctr, Richard L Solove Res Inst,Dept Radiat Oncol, Wiseman Hall 385G,410 W 12th Ave, Columbus, OH 43210 USA. EM TL@osumc.edu FU RTOG [U10 CA21661]; CCOP from the National Cancer Institute (NCI) [U10 CA37422]; Pennsylvania Department of Health [4100054841]; Ohio State University Comprehensive Cancer Center FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG), and was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). The publication was supported by the 2010 Pennsylvania Department of Health Formula Grant 4100054841 (to AG), and funds from the Ohio State University Comprehensive Cancer Center (to AC). This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. We thank Vaia Dedousi-Huebner for writing and editorial assistance. NR 0 TC 7 Z9 9 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2013 VL 18 IS 6 BP 685 EP 686 DI 10.1634/theoncologist.2012-0461 PG 2 WC Oncology SC Oncology GA 172YL UT WOS:000321043200013 PM 23728940 ER PT J AU Luke, JJ Hodi, FS AF Luke, Jason J. Hodi, F. Stephen TI Ipilimumab, Vemurafenib, Dabrafenib, and Trametinib: Synergistic Competitors in the Clinical Management of BRAF Mutant Malignant Melanoma SO ONCOLOGIST LA English DT Article DE CTLA-4; Immunotherapy; BRAF; MEK; Resistance; Biomarker ID T-LYMPHOCYTE ANTIGEN-4; DOSE-ESCALATION TRIAL; RAF INHIBITOR RESISTANCE; UNRESECTABLE STAGE-III; METASTATIC MELANOMA; PHASE-II; CTLA-4 BLOCKADE; OPEN-LABEL; COMBINATION IMMUNOTHERAPY; SELECTIVE INHIBITOR AB There have been significant advances in the treatment of malignant melanoma with the U.S. Food and Drug Administration approval of two drugs in 2011, the first drugs approved in 13 years. The developments of immune checkpoint modulation via cytotoxic T-lymphocyte antigen-4 blockade, with ipilimumab, and targeting of BRAF(V600), with vemurafenib or dabrafenib, as well as MEK, with trametinib, have been paradigm changing both for melanoma clinical practice and for oncology therapeutic development. These advancements, however, reveal new clinical questions regarding combinations and optimal sequencing of these agents in patients with BRAF mutant disease. We review the development of these agents, putative biomarkers, and resistance mechanisms relevant to their use, and possibilities for sequencing and combining these agents. C1 [Luke, Jason J.] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Luke, JJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jason_Luke@dfci.harvard.edu FU Bristol-Myers Squibb; Genentech/Roche; Novartis; Pfizer; Synta FX The authors are fully responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. The authors wish to acknowledge StemScientific for providing editorial support. This support was funded by Bristol-Myers Squibb. Neither Bristol-Myers Squibb nor StemScientific influenced the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript.; F. Stephen Hodi: Genentech/Roche, Bristol-Myers Squibb, Novartis, Pfizer, and Synta (RF); Genentech/Roche, Novartis, and Bristol-Myers Squibb (C/A). The other author indicated no financial relationships. NR 72 TC 35 Z9 37 U1 0 U2 13 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2013 VL 18 IS 6 BP 717 EP 725 DI 10.1634/theoncologist.2012-0391 PG 9 WC Oncology SC Oncology GA 172YL UT WOS:000321043200018 PM 23709751 ER PT J AU Postow, MA Luke, JJ Bluth, DJ Ramaiya, N Panageas, KS Lawrence, DP Ibrahim, N Flaherty, KT Sullivan, RJ Ott, PA Callahan, DK Harding, JJ D'Angelo, SP Dickson, AA Schwartz, GK Chapman, PB Gnjatic, S Wolchok, JD Hodi, FS Carvajal, RD AF Postow, Michael A. Luke, Jason J. Bluth, Mark J. Ramaiya, Nikhil Panageas, Katherine S. Lawrence, Donald P. Ibrahim, Nageatte Flaherty, Keith T. Sullivan, Ryan J. Ott, Patrick A. Callahan, Margaret K. Harding, James J. D'Angelo, Sandra P. Dickson, Mark A. Schwartz, Gary K. Chapman, Paul B. Gnjatic, Sacha Wolchok, Jedd D. Hodi, F. Stephen Carvajal, Richard D. TI Ipilimumab for Patients With Advanced Mucosal Melanoma SO ONCOLOGIST LA English DT Article DE Mucosal melanoma; Ipilimumab; CTLA-4; Immunotherapy; Cancer-testis antigens ID KIT PROTEIN EXPRESSION; METASTATIC MELANOMA; ANTIGEN CT45; HUMAN CANCER; BIOCHEMOTHERAPY; MUTATIONS; DACARBAZINE; LYMPHOMAS; SURVIVAL; THERAPY AB The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma. C1 [Postow, Michael A.; Callahan, Margaret K.; Harding, James J.; D'Angelo, Sandra P.; Dickson, Mark A.; Schwartz, Gary K.; Chapman, Paul B.; Wolchok, Jedd D.; Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Bluth, Mark J.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Luke, Jason J.; Ibrahim, Nageatte; Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Ramaiya, Nikhil] Dana Farber Brigham & Womens Canc Ctr, Dept Radiol, Boston, MA USA. [Lawrence, Donald P.; Flaherty, Keith T.; Sullivan, Ryan J.] Massachusetts Gen Hosp Canc Ctr, Dept Med, Boston, MA USA. [Gnjatic, Sacha] Ludwig Inst Canc Res, New York, NY USA. [Gnjatic, Sacha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA. RP Carvajal, RD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma Sarcoma Oncol Serv, BAIC 1071, New York, NY 10021 USA. EM carvajar@mskcc.org FU National Institutes of Health [RC2CA148468]; Melanoma Research Alliance; Swim Across America; Cancer Research Institute; Lita Annenberg Hazen Foundation; Commonwealth Foundation for Cancer Research; Clinical and Translational Science Center at Weill Cornell Medical College [UL1-TR000457]; Bristol-Myers Squibb FX This study was supported by grants from the National Institutes of Health (RC2CA148468), the Melanoma Research Alliance, Swim Across America, the Cancer Research Institute, the Lita Annenberg Hazen Foundation, and the Commonwealth Foundation for Cancer Research. This investigation was supported by grant UL1-TR000457 of the Clinical and Translational Science Center at Weill Cornell Medical College.; Margaret K. Callahan: Bristol-Myers Squibb (RF); Jedd D. Wolchok: Bristol-Myers Squibb (C/A, RF); F. Stephen Hodi: Bristol-Myers Squibb (C/A, RF); Richard D. Carvajal: Bristol-Myers Squibb (RF). NR 29 TC 36 Z9 36 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2013 VL 18 IS 6 BP 726 EP 732 DI 10.1634/theoncologist.2012-0464 PG 7 WC Oncology SC Oncology GA 172YL UT WOS:000321043200019 PM 23716015 ER PT J AU Fecher, LA Agarwala, SS Hodi, FS Weber, JS AF Fecher, Leslie A. Agarwala, Sanjiv S. Hodi, F. Stephen Weber, Jeffrey S. TI Ipilimumab and Its Toxicities: A Multidisciplinary Approach SO ONCOLOGIST LA English DT Article DE Ipilimumab; CTLA-4; Antibody; Melanoma; Immune-mediated toxicity; immune-related adverse events; AEOSI ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; METASTATIC MELANOMA; ANTI-CTLA-4 ANTIBODY; AUTOIMMUNE HYPOPHYSITIS; MONOCLONAL-ANTIBODY; INDUCED SARCOIDOSIS; CLINICAL-RESPONSE; ADVERSE EVENTS; PHASE-II; CANCER AB The treatment for metastatic melanoma has evolved significantly in the past few years. Ipilimumab, an immunotherapy, is now in mainstream oncology practice given that it has shown improved overall survival in randomized clinical trials. Other immune modulating agents, such as programmed death receptor-1 and programmed death receptor ligand-1 antibodies, are showing promise in early clinical trials. This manuscript will review ipilimumab and its most common side effects. Immune-related adverse events (irAEs) are important to recognize early, and their presentation, timing of onset, and general recommendations for workup and management will be reviewed. Assembling a multidisciplinary team, as well as thorough education of the patient, is recommended to optimize patient care. C1 [Fecher, Leslie A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Agarwala, Sanjiv S.] St Lukes Canc Ctr, Bethlehem, PA USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weber, Jeffrey S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Fecher, LA (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,Room 473, Indianapolis, IN 46202 USA. EM lafecher@iu.edu FU Bristol-Myers Squibb; Genentech-Roche; sanofi-aventis FX The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. The authors also wish to acknowledge Jennifer Wietzke, Ph.D., and Rebecca Goldstein, Ph.D., from StemScientific, funded by Bristol-Myers Squibb, for providing editorial support. Neither Bristol-Myers Squibb nor StemScientific influenced the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript.; Leslie Fecher: Genentech-Roche, Bristol-Myers Squibb (C/A); Imedex LLC, Dava Oncology, First Consult LLC (H); Genentech-Roche, sanofi-aventis, Bristol-Myers Squibb (RF); F. Stephen Hodi: Bristol-Myers Squibb (C/A, RF); Jeffrey S. Weber: Bristol-Myers Squibb (RF, H). NR 56 TC 73 Z9 75 U1 1 U2 11 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 JUN PY 2013 VL 18 IS 6 BP 733 EP 743 DI 10.1634/theoncologist.2012-0483 PG 11 WC Oncology SC Oncology GA 172YL UT WOS:000321043200020 PM 23774827 ER PT J AU Taylor, JW Chi, AS Cahill, DP AF Taylor, Jennie W. Chi, Andrew S. Cahill, Daniel P. TI Tailored Therapy in Diffuse Gliomas: Using Molecular Classifiers to Optimize Clinical Management SO ONCOLOGY-NEW YORK LA English DT Review ID BRAIN-TUMOR GROUP; IDH2 MUTATIONS; ISOCITRATE DEHYDROGENASE; GLIOBLASTOMA-MULTIFORME; ONCOMETABOLITE 2-HYDROXYGLUTARATE; GRADE GLIOMA; RESECTION; OLIGODENDROGLIOMA; SURVIVAL; EXTENT AB Diffuse gliomas are the most common primary malignant brain tumors in adults and continue to be almost universally fatal. Nevertheless, a striking variability in outcome has long been observed, with a subset of patients having prolonged survival. Recent molecular discoveries have provided new insights into gliomagenesis and have enhanced clinical subclassification of gliomas. Mutations in the isocitrate dehydrogenase (IDH) genes occur frequently in low-grade astrocytomas and oligodendrogliomas (World Health Organization [WHO] grade II), and in higher-grade gliomas (WHO grades III and IV) that arise after malignant progression of low-grade tumors. IDH mutation has an established role as a favorable prognostic marker; however, the utility of IDH mutation in guiding treatment is still under investigation. A subset of IDH-mutant tumors, predominantly oligodendrogliomas, also harbor codeletion of chromosomes 1 p and 19q, a feature that predicts responsiveness to chemotherapy. Here, we review the current data regarding the prognostic and predictive value of IDH mutation and 1 p/19q codeletion in gliomas. We also discuss possible management algorithms using these biomarkers to tailor surgical and adjuvant therapy for specific diffuse gliomas. Ultimately, understanding the natural history of glioma subtypes and the predictive value of genetic markers may maximize survival and minimize treatment morbidity. C1 [Taylor, Jennie W.; Chi, Andrew S.] Massachusetts Gen Hosp, Ctr Canc, Div Neurooncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA. [Taylor, Jennie W.; Chi, Andrew S.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA. [Cahill, Daniel P.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurosurg, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Taylor, Jennie W.; Chi, Andrew S.; Cahill, Daniel P.] Harvard Univ, Sch Med, Boston, MA USA. RP Cahill, DP (reprint author), Massachusetts Gen Hosp, 55 Fruit St Yawkey 9E, Boston, MA 02114 USA. EM dcahill@partners.org NR 51 TC 7 Z9 8 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2013 VL 27 IS 6 BP 504 EP 514 PG 11 WC Oncology SC Oncology GA 174MH UT WOS:000321159200002 PM 23909061 ER PT J AU Jeon, JY Meyerhardt, JA AF Jeon, Justin Y. Meyerhardt, Jeffrey A. TI Exercise After Cancer Diagnosis: Time to Get Moving THE LEMANNE/CASSILETH/GUBILI ARTICLE REVIEWED SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; SURVIVORS; INTERVENTION; GUIDELINES; TRIAL; RISK; NUTRITION; INSULIN; IMPACT C1 [Jeon, Justin Y.] Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Jeon, JY (reprint author), Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. NR 18 TC 1 Z9 1 U1 0 U2 3 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2013 VL 27 IS 6 BP 585 EP + PG 3 WC Oncology SC Oncology GA 174MH UT WOS:000321159200015 PM 23909074 ER PT J AU Ciolino, JB Belin, MW Todani, A Al-Arfaj, K Rudnisky, CJ AF Ciolino, Joseph B. Belin, Michael W. Todani, Amit Al-Arfaj, Khalid Rudnisky, Christopher J. CA Boston Keratoprosthesis Type 1 TI Retention of the Boston Keratoprosthesis Type 1: Multicenter Study Results SO OPHTHALMOLOGY LA English DT Article ID UNIVERSITY-OF-CALIFORNIA; COMPLICATIONS; OUTCOMES; DAVIS AB Objective: To report the retention rate of the Boston keratoprosthesis type 1 and to identify risk factors for keratoprosthesis loss. Design: Cohort study. Participants: A total of 300 eyes of 300 patients who underwent implantation of the Boston keratoprosthesis type I device between January 2003 and July 2008 by 19 surgeons at 18 medical centers. Methods: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site. Main Outcome Measures: Keratoprosthesis retention. Results: A total cumulative number of 422 life-years of device implantation are included in this analysis. The average duration of follow-up was 17.1+/-14.8 months, with a range of 1 week to >6.1 years. Ninety-three percent of the 300 Boston keratoprosthesis implants were retained at their last follow-up, corresponding to a retention time of 396 patient-years or 1.42 years/keratoprosthesis. The probability of retention after 1 year and 2 years was 94% and 89%, respectively. During the study period, 21 (7%) eyes failed to retain the device; the reasons for keratoprosthesis loss include sterile keratolysis (9), fungal infections (8), dense retroprosthetic membranes (3), and bacterial endophthalmitis (1). Multivariate analysis demonstrated 3 independent risk factors for keratoprosthesis loss: autoimmune cause (hazard ratio [HR], 11.94; 95% confidence interval [CI], 3.31-43.11), ocular surface exposure requiring a concomitant tarsorrhaphy (HR, 3.43; 95% CI, 1.05-11.22), and number of prior failed penetrating keratoplasties (HR, 1.64; 95% CI, 1.18-2.28). Conclusions: The Boston keratoprosthesis type 1 seems to be a viable option for eyes that are not candidates for penetrating keratoplasty (PK). Ocular surface disease due to an autoimmune cause demonstrated the lowest retention rate. (C) 2013 by the American Academy of Ophthalmology. C1 [Ciolino, Joseph B.; Todani, Amit; Al-Arfaj, Khalid] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Ciolino, Joseph B.; Belin, Michael W.; Todani, Amit] Albany Med Coll, Dept Ophthalmol, Albany Med Ctr, Albany, NY 12208 USA. [Belin, Michael W.] Univ Arizona, Dept Ophthalmol, Tucson, AZ USA. [Al-Arfaj, Khalid] Dammam Univ, Dept Ophthalmol, Dammam, Saudi Arabia. [Rudnisky, Christopher J.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. RP Ciolino, JB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Joseph_Ciolino@meei.harvard.edu FU National Eye Institute [1K08EY019686-03]; New England Cornea Transplant Research Fund; Research to Prevent Blindness Career Development Award; Lion's Club of Massachusetts FX Supported by National Eye Institute 1K08EY019686-03 (J.B.C.), New England Cornea Transplant Research Fund (J.B.C.), Research to Prevent Blindness Career Development Award (J.B.C.), and Lion's Club of Massachusetts (J.B.C.). NR 13 TC 56 Z9 57 U1 0 U2 5 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 JUN PY 2013 VL 120 IS 6 BP 1195 EP 1200 DI 10.1016/j.ophtha.2012.11.025 PG 6 WC Ophthalmology SC Ophthalmology GA 167RJ UT WOS:000320650700024 PM 23499061 ER PT J AU Colby, K Pavan-Langston, D AF Colby, Kathryn Pavan-Langston, Deborah TI Oral Acyclovir for Herpes Simplex Blepharoconjunctivitis in Children Reply SO OPHTHALMOLOGY LA English DT Letter C1 [Colby, Kathryn; Pavan-Langston, Deborah] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Colby, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2013 VL 120 IS 6 BP E28 EP E9 PG 2 WC Ophthalmology SC Ophthalmology GA 167RJ UT WOS:000320650700002 PM 23732060 ER PT J AU Yoon, MK McCulley, TJ Horton, JC AF Yoon, Michael K. McCulley, Timothy J. Horton, Jonathan C. TI Brow Ptosis After Temporal Artery Biopsy SO OPHTHALMOLOGY LA English DT Letter C1 [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. [McCulley, Timothy J.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA. [Horton, Jonathan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Horton, Jonathan C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Horton, Jonathan C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA. RP Yoon, MK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 2013 VL 120 IS 6 BP E34 EP E34 PG 1 WC Ophthalmology SC Ophthalmology GA 167RJ UT WOS:000320650700010 PM 23732069 ER PT J AU Andrews, JR Prajapati, KG Eypper, E Shrestha, P Shakya, M Pathak, KR Joshi, N Tiwari, P Risal, M Koirala, S Karkey, A Dongol, S Wen, S Smith, AB Maru, D Basnyat, B Baker, S Farrar, J Ryan, ET Hohmann, E Arjyal, A AF Andrews, Jason R. Prajapati, Krishna G. Eypper, Elizabeth Shrestha, Poojan Shakya, Mila Pathak, Kamal R. Joshi, Niva Tiwari, Priyanka Risal, Manisha Koirala, Samir Karkey, Abhilasha Dongol, Sabina Wen, Shawn Smith, Amy B. Maru, Duncan Basnyat, Buddha Baker, Stephen Farrar, Jeremy Ryan, Edward T. Hohmann, Elizabeth Arjyal, Amit TI Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID BONE-MARROW; BLOOD CULTURE; DIAGNOSIS; TYPHI; EFFICACY; BROTH; BACT/ALERT; PARATYPHI; KATHMANDU; COUNTRIES AB Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings: Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories. C1 [Andrews, Jason R.; Eypper, Elizabeth; Ryan, Edward T.; Hohmann, Elizabeth] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Andrews, Jason R.; Maru, Duncan; Ryan, Edward T.; Hohmann, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Prajapati, Krishna G.; Shrestha, Poojan; Shakya, Mila; Pathak, Kamal R.; Joshi, Niva; Tiwari, Priyanka; Risal, Manisha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Basnyat, Buddha; Arjyal, Amit] Univ Oxford, Patan Hosp, Patan Acad Hlth Sci, Clin Res Unit, Kathmandu, Nepal. [Wen, Shawn; Smith, Amy B.] MIT, Lab D, Cambridge, MA USA. [Maru, Duncan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Baker, Stephen; Farrar, Jeremy] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Baker, Stephen; Farrar, Jeremy] Univ Oxford, Ctr Trop Med, Oxford, England. [Baker, Stephen] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jandrews6@partners.org OI Farrar, Jeremy/0000-0002-2700-623X FU Frederick Lovejoy Fund at Boston Children's Hospital; Harvard Global Health Institute; Li Ka Shing Foundation; National Institute of Allergy and Infectious Diseases [AI100023, AI077883] FX This study was supported by the Frederick Lovejoy Fund at Boston Children's Hospital, Harvard Global Health Institute, the Li Ka Shing Foundation, and the National Institute of Allergy and Infectious Diseases (AI100023 and AI077883). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 7 Z9 7 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2013 VL 7 IS 6 AR e2292 DI 10.1371/journal.pntd.0002292 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 175AL UT WOS:000321201300043 PM 23853696 ER PT J AU Sinclair, SJ Slavin-Mulford, J Antonius, D Stein, MB Siefert, CJ Haggerty, G Malone, JC O'Keefe, S Blais, MA AF Sinclair, Samuel Justin Slavin-Mulford, Jenelle Antonius, Daniel Stein, Michelle B. Siefert, Caleb J. Haggerty, Greg Malone, Johanna C. O'Keefe, Sheila Blais, Mark A. TI Development and Preliminary Validation of the Level of Care Index (LOCI) From the Personality Assessment Inventory (PAI) in a Psychiatric Sample SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE Level of Care Index; LOCI; psychiatric hospitalization; personality assessment inventory; PAI ID OBJECT RELATIONS SCALE; SUICIDE ATTEMPTERS; PSYCHOMETRIC PROPERTIES; HOSPITAL UTILIZATION; SERVICE UTILIZATION; INPATIENT SERVICE; SOCIAL COGNITION; CLINICAL UTILITY; SUBSTANCE-ABUSE; NORMATIVE DATA AB Research over the last decade has been promising in terms of the incremental utility of psychometric tools in predicting important clinical outcomes, such as mental health service utilization and inpatient psychiatric hospitalization. The purpose of this study was to develop and validate a new Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI). Logistic regression was initially used in a development sample (n = 253) of psychiatric patients to identify unique PAI indicators associated with inpatient (n = 75) as opposed to outpatient (n = 178) status. Five PAI variables were ultimately retained (Suicidal Ideation, Antisocial Personality-Stimulus Seeking, Paranoia-Persecution, Negative Impression Management, and Depression-Affective) and were then aggregated into a single LOCI and independently evaluated in a second validation sample (n = 252). Results indicated the LOCI effectively differentiated inpatients from outpatients after controlling for demographic variables and was significantly associated with both internalizing and externalizing risk factors for psychiatric admission (range of ds = 0.46 for history of arrests to 0.88 for history of suicidal ideation). The LOCI was additionally found to be meaningfully associated with measures of normal personality, performance-based tests of psychological functioning, and measures of neurocognitive (executive) functioning. The clinical implications of these findings and potential utility of the LOCI are discussed. C1 [Sinclair, Samuel Justin; Slavin-Mulford, Jenelle; Stein, Michelle B.; Malone, Johanna C.; O'Keefe, Sheila; Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sinclair, Samuel Justin; Stein, Michelle B.; Malone, Johanna C.; O'Keefe, Sheila; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Antonius, Daniel] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY USA. [Antonius, Daniel] NYU, Dept Psychiat, Sch Med, New York, NY 10003 USA. [Siefert, Caleb J.] Univ Michigan Dearborn, Dept Behav Sci, Dearborn, MI 48128 USA. [Haggerty, Greg] Nassau Univ, Von Tauber Inst Global Psychiat, Med Ctr, E Meadow, NY USA. RP Sinclair, SJ (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq 7th Floor, Boston, MA 02114 USA. EM SJSinclair@Partners.org NR 63 TC 4 Z9 4 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD JUN PY 2013 VL 25 IS 2 BP 606 EP 617 DI 10.1037/a0032085 PG 12 WC Psychology, Clinical SC Psychology GA 173DR UT WOS:000321058800027 PM 23458082 ER PT J AU Hartwell, KJ Prisciandaro, JJ Borckardt, J Li, XB George, MS Brady, KT AF Hartwell, Karen J. Prisciandaro, James J. Borckardt, Jeffery Li, Xingbao George, Mark S. Brady, Kathleen T. TI Real-Time fMRI in the Treatment of Nicotine Dependence: A Conceptual Review and Pilot Studies SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE real-time fMRI; real-time fMRI feedback; neurofeedback; nicotine dependence ID CORTEX ACTIVITY; FUNCTIONAL MRI; ACTIVATION; SMOKERS; NEUROFEEDBACK; BIOFEEDBACK; MODULATION; INTERFACE; RELAPSE AB Technical advances allowing for the analysis of functional MRI (fMRI) results in real time have led to studies exploring the ability of individuals to use neural feedback signals to modify behavior and regional brain activation. The use of real-time fMRI (rtfMRI) feedback has been explored for therapeutic benefit in a number of disease states, but to our knowledge, the potential therapeutic benefit of rtfMRI feedback in the treatment of addictive disorders has not been explored. This article will provide an overview of the development of rtfMRI and discussion of its potential uses in the treatment of addictions. We also describe a series of pilot studies that highlight some of the technical challenges in developing a rtfMRI feedback paradigm for use in addictions, specifically in nicotine dependence. Because the use of rtfMRI feedback is in its infancy, the work described is focused on establishing some of the basic parameters in optimizing the rtfMRI feedback, such as the type of feedback signal, region of interest for feedback and predicting which subjects are most likely to respond well to training. While rtfMRI feedback remains an intriguing possibility for the treatment of addictions, much work remains to be done in establishing its efficacy. C1 [Hartwell, Karen J.; Prisciandaro, James J.; Borckardt, Jeffery; Li, Xingbao; George, Mark S.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Hartwell, Karen J.; George, Mark S.; Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC USA. RP Hartwell, KJ (reprint author), Med Univ S Carolina, 67 President St,MSC 861, Charleston, SC 29425 USA. EM hartwelk@musc.edu FU NIDA NIH HHS [R33 DA026085, R33 DA026085-04, R33 DA036085-03] NR 45 TC 12 Z9 12 U1 2 U2 14 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2013 VL 27 IS 2 SI SI BP 501 EP 509 DI 10.1037/a0028215 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 170HS UT WOS:000320841600017 PM 22564200 ER PT J AU Schellhammer, PF Chodak, G Whitmore, JB Sims, R Frohlich, MW Kantoff, PW AF Schellhammer, Paul F. Chodak, Gerald Whitmore, James B. Sims, Robert Frohlich, Mark W. Kantoff, Philip W. TI Lower Baseline Prostate-specific Antigen Is Associated With a Greater Overall Survival Benefit From Sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) Trial SO UROLOGY LA English DT Article ID MITOXANTRONE PLUS PREDNISONE; CANCER; MEN; CORRELATE; ANEMIA AB OBJECTIVE To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial who were randomized to receive sipuleucel-T or control. METHODS The most powerful of these prognostic factors, baseline prostate-specific antigen (PSA), was subdivided into quartiles to evaluate treatment effect patterns. Cox regression analyses were used to assess predictors of overall survival (OS) and sipuleucel-T treatment effect within PSA quartiles. Median OS was estimated by the Kaplan-Meier method. RESULTS PSA was the strongest baseline prognostic factor (P<.0001). Furthermore, the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA. The OS hazard ratio for patients in the lowest baseline PSA quartile (<= 22.1 ng/mL) was 0.51 (95% confidence interval, 0.31-0.85) compared with 0.84 (95% confidence interval, 0.55-1.29) for patients in the highest PSA quartile (>134 ng/mL). Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile. Estimated 3-year survival in the lowest PSA quartile was 62.6% for sipuleucel-T patients and 41.6% for control patients, representing a 50% relative increase. CONCLUSION The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors, particularly those with lower baseline PSA values. These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer. (C) 2013 Elsevier Inc. C1 Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA. Weiss Mem Hosp, Midwest Prostate & Urol Hlth Ctr, Chicago, IL USA. Dendreon Corp, Seattle, WA USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM philip_kantoff@dfci.harvard.edu FU Dendreon Corporation FX This study was funded by Dendreon Corporation. NR 24 TC 70 Z9 73 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD JUN PY 2013 VL 81 IS 6 BP 1297 EP 1302 DI 10.1016/j.urology.2013.01.061 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 167BN UT WOS:000320605400061 PM 23582482 ER PT J AU Najafzadeh, M Marra, CA Lynd, L Wiseman, S AF Najafzadeh, Mehdi Marra, Carlo A. Lynd, Larry Wiseman, Sam TI Authors' Response to "Comparative Effectiveness and Personalized Medicine" by Dr. JC Hornberger SO VALUE IN HEALTH LA English DT Letter C1 [Najafzadeh, Mehdi] Mass Gen Hosp, Mongan Inst, Boston, MA USA. [Marra, Carlo A.; Lynd, Larry] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Wiseman, Sam] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. RP Najafzadeh, M (reprint author), Mass Gen Hosp, Mongan Inst, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2013 VL 16 IS 4 BP 697 EP 697 DI 10.1016/j.jval.2013.02.005 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 178IK UT WOS:000321440900030 PM 23796305 ER PT J AU Patel, MS Arron, MJ Sinsky, TA Green, EH Baker, DW Bowen, JL Day, S AF Patel, Mitesh S. Arron, Martin J. Sinsky, Thomas A. Green, Eric H. Baker, David W. Bowen, Judith L. Day, Susan TI Estimating the Staffing Infrastructure for a Patient-Centered Medical Home SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; HEALTH-CARE; GLYCEMIC CONTROL; COST SAVINGS; INNOVATION; SERVICES; QUALITY; MODEL; MANAGEMENT AB Background:The patient-centered medical home (PCMH) offers an innovative method of delivering primary care. However, the necessary staffing infrastructure is not well established. Objectives: To evaluate the roles of personnel within a PCMH and to propose necessary staffing ratios and associated incremental costs to implement this model of care. Methods: We sampled primary care clinical practices that either have successfully deployed or were in the process of implementing a PCMH practice model. We conducted targeted interviews of administrators from these practices and reviewed published literature on the personnel roles within a PCMH. Collectively, these data were compared with current staffing standards and used to inform an analytical model and sensitivity analysis. Results: Primary care practices that successfully transitioned to a PCMH have incorporated a range of new staff and functionalities. Based on our model, we estimated that 4.25 full-time equivalents (FTEs) should be allocated to staffing personnel per 1 physician FTE. Compared with the base-case model of current staffing in the United States of 2.68 FTEs per physician FTE, this is a 59% increase. After applying sensitivity analysis for variability in staffing and compensation, the incremental staffing FTE per physician FTE was 1.57 (range 1.41-1.73) and the incremental associated cost per member per month was $4.68 (range $3.79-$6.43). Conclusions: Our study suggests that additional staff with specific expertise and training is necessary to implement a PCMH. Further study and opportunities for funding additional staffing costs will be important for realizing the potential of the PCMH model of care. C1 [Patel, Mitesh S.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Patel, Mitesh S.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Day, Susan] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Arron, Martin J.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Sinsky, Thomas A.] Med Associates, Dubuque, IA USA. [Green, Eric H.] Mercy Catholic Med Ctr, Darby, PA USA. [Baker, David W.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Bowen, Judith L.] Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97201 USA. RP Patel, MS (reprint author), Univ Penn, 423 Guardian Dr,13th Fl, Philadelphia, PA 19104 USA. EM mpatel@mail.med.upenn.edu NR 47 TC 19 Z9 19 U1 2 U2 10 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 JUN PY 2013 VL 19 IS 6 BP 509 EP 516 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 171FO UT WOS:000320910700005 PM 23844711 ER PT J AU Dukkipati, SR Kuck, KH Neuzil, P Woollett, I Kautzner, J McElderry, HT Schmidt, B Gerstenfeld, EP Doshi, SK Horton, R Metzner, A d'Avila, A Ruskin, JN Natale, A Reddy, VY AF Dukkipati, Srinivas R. Kuck, Karl-Heinz Neuzil, Petr Woollett, Ian Kautzner, Josef McElderry, H. Thomas Schmidt, Boris Gerstenfeld, Edward P. Doshi, Shephal K. Horton, Rodney Metzner, Andreas d'Avila, Andre Ruskin, Jeremy N. Natale, Andrea Reddy, Vivek Y. TI Pulmonary Vein Isolation Using a Visually Guided Laser Balloon Catheter: The First 200-Patient Multicenter Clinical Experience SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; lasers; pulmonary vein isolation; visual guidance ID PAROXYSMAL ATRIAL-FIBRILLATION; VENOUS ISOLATION; ABLATION; FEASIBILITY; CRYOBALLOON AB Background Because of the technical difficulty with achieving pulmonary vein (PV) isolation in the treatment of patients with paroxysmal atrial fibrillation, novel catheter designs to facilitate the procedure are in development. A visually guided laser ablation (VGLA) catheter was designed to allow the operator to directly visualize target tissue for ablation and then deliver laser energy to perform point-to-point circumferential ablation. Single-center studies have demonstrated favorable safety and efficacy. We sought to determine the multicenter feasibility, efficacy, and safety of performing PV isolation using the VGLA catheter. Methods and Results This study includes the first 200 paroxysmal atrial fibrillation patients treated with the VGLA catheter (33 operators, 15 centers). After transseptal puncture, the VGLA catheter was used to perform PV isolation. Electric isolation was assessed using a circular mapping catheter. Using the VGLA catheter, 98.8% (95% confidence interval, 97.8%-99.5%) of targeted PVs were isolated using a mean of 1.07 catheters per patient. Fluoroscopy and procedure times were 31 +/- 21 (mean +/- SD) and 200 +/- 54 minutes, respectively, and improved with operator experience. There were no instances of stroke, transient ischemic attack, atrioesophageal fistulas, or significant PV stenosis. There was a 2% incidence of cardiac tamponade and a 2.5% incidence of phrenic nerve palsy. At 12 months, the drug-free rate of freedom from atrial arrhythmias after 1 or 2 procedures was 60.2% (95% confidence interval, 52.7%-67.4%). Conclusions In this multicenter experience of the first 200 patients treated with the VGLA catheter, PV isolation can be achieved in virtually all patients using a single VGLA catheter with an efficacy similar to radiofrequency ablation. C1 [Dukkipati, Srinivas R.; d'Avila, Andre; Reddy, Vivek Y.] Mt Sinai Sch Med, Helmsley Electrophysiol Ctr, New York, NY 10029 USA. [Kuck, Karl-Heinz; Metzner, Andreas] Asklepios Klin St Georg, Hamburg, Germany. [Neuzil, Petr] Homolka Hosp, Prague, Czech Republic. [Woollett, Ian] Sentara Cardiovasc Res Inst, Norfolk, VA USA. [Kautzner, Josef] IKEM, Prague, Czech Republic. [McElderry, H. Thomas] Univ Alabama Birmingham, Birmingham, AL USA. [Schmidt, Boris] Cardioangiol Ctr Bethanien CCB, Frankfurt, Germany. [Gerstenfeld, Edward P.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Doshi, Shephal K.] Pacific Heart Inst, Santa Monica, CA USA. [Horton, Rodney; Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Mt Sinai Sch Med, Helmsley Electrophysiol Ctr, 1 Gustave L Levy Pl,Box 1030, 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 CardioFocus, Inc. FX This study was supported by CardioFocus, Inc. NR 17 TC 32 Z9 35 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JUN PY 2013 VL 6 IS 3 BP 467 EP 472 DI 10.1161/CIRCEP.113.000431 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 169EH UT WOS:000320760200012 PM 23559674 ER PT J AU Gao, XL Wang, HZ Yang, J Liu, ZR AF Gao, Xueliang Wang, Haizhen Yang, Jenny Liu, Zhi-Ren TI Prevent protein interactions to prevent cancer metastasis SO EXPERT REVIEW OF PROTEOMICS LA English DT Editorial Material DE cancer metastasis; drug discovery; drug targets; inhibitor; protein-protein interaction ID DRUG DISCOVERY; TUMOR-GROWTH; IN-VIVO; BREAST; ANGIOGENESIS; INHIBITION; ACTIVATION; RECEPTOR; BIOLOGY C1 [Gao, Xueliang; Wang, Haizhen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yang, Jenny] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. [Liu, Zhi-Ren] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. RP Gao, XL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM xueliang_gao@dfci.harvard.edu NR 21 TC 1 Z9 1 U1 1 U2 6 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD JUN PY 2013 VL 10 IS 3 BP 207 EP 209 DI 10.1586/EPR.13.17 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 168LU UT WOS:000320708200001 PM 23777209 ER PT J AU Halczli, A Woolley, AB AF Halczli, Alyssa Woolley, Adam B. TI Medication underdosing and underprescribing: Issues that may contribute to polypharmacy, poor outcomes SO FORMULARY LA English DT Article AB Medication underdosing and underprescribing are often overlooked and can result in poor patient outcomes. They can also contribute to polypharmacy and significant cost to the healthcare system. Pharmacists can play a key role in preventing underdosing and underprescribing of medications by ensuring that patient-specific pharmacotherapy is prescribed and administered, and by providing patient and provider education regarding appropriate use of medications. While numerous examples of effective pharmacist-led interventions to reduce medication underdosing and underprescribing are described in the literature, further research is needed to elucidate new ways to improve patient outcomes and reduce unnecessary cost to the healthcare system. This article describes the clinical consequences of medication underdosing and underprescribing and provides examples of pharmacist-led interventions to address these medication issues. C1 [Halczli, Alyssa; Woolley, Adam B.] VA Boston Healthcare Syst, Boston, MA USA. [Woolley, Adam B.] Northeastern Univ, Sch Pharm, Dept Pharm Serv, Bouve Coll Hlth Sci, Boston, MA 02115 USA. RP Halczli, A (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 1082-801X J9 FORMULARY JI Formulary PD JUN PY 2013 VL 48 IS 6 BP 194 EP 196 PG 3 GA 170EH UT WOS:000320832400010 ER PT J AU Thiagarajan, P Afshar-Kharghan, V AF Thiagarajan, Perumal Afshar-Kharghan, Vahid TI Platelet Transfusion Therapy SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Platelet transfusion; Alloimmunization; Transfusion triggers; Pathogen reduction ID THROMBOTIC THROMBOCYTOPENIC PURPURA; MEMBRANE PHOSPHOLIPID ASYMMETRY; PATHOGEN INACTIVATION; STORED PLATELETS; CROSS-MATCH; PHOSPHATIDYLSERINE EXPOSURE; APHERESIS PLATELETS; BLEEDING DIATHESIS; BLOOD-PLATELETS; ACUTE-LEUKEMIA AB Platelet transfusion therapy has become an integral part of the treatment of patients with hematological and solid tumor malignancy receiving chemotherapy. Since its introduction almost 60 years ago, several advances and refinements have been introduced in the collection, storage, and administration to improve the safety and efficacy of platelet transfusion. This review summarizes the current practice and clinical approach to patients with thrombocytopenia. Existing evidence-based guidelines for appropriate platelet transfusion is reviewed. C1 [Thiagarajan, Perumal] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA. [Thiagarajan, Perumal] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Afshar-Kharghan, Vahid] MD Anderson Canc Ctr, Sect Benign Hematol, Houston, TX 77030 USA. RP Thiagarajan, P (reprint author), Michael E DeBakey VA Med Ctr, Mail Stop 113,2002 Holcombe Blvd, Houston, TX 77030 USA. EM perumalt@bcm.edu OI Thiagarajan, Perumal/0000-0003-2186-7036 FU Veterans Affairs Research Service FX Supported by a grant from the Veterans Affairs Research Service (P. Thiagarajan). NR 103 TC 12 Z9 12 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 2013 VL 27 IS 3 BP 629 EP + DI 10.1016/j.hoc.2013.03.004 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 168XJ UT WOS:000320740900012 PM 23714315 ER PT J AU Higgins, HW Jenkins, J Horn, TD Kroumpouzos, G AF Higgins, H. William Jenkins, Jennifer Horn, Thomas D. Kroumpouzos, George TI Pregnancy-Associated Hyperkeratosis of the Nipple A Report of 25 Cases SO JAMA DERMATOLOGY LA English DT Article ID NEVOID HYPERKERATOSIS; ACANTHOSIS NIGRICANS; HYPER-KERATOSIS; UNILATERAL HYPERKERATOSIS; TOPICAL CALCIPOTRIOL; AREOLA AB Importance: Reported physiologic nipple changes in pregnancy do not include hyperkeratosis and are expected to resolve or improve post partum. Hyperkeratosis of the nipple and/or areola can develop in the context of inflammatory diseases (such as atopic dermatitis), in acanthosis nigricans, as an extension of epidermal nevus, after estrogen treatment, and/or in nevoid hyperkeratosis of the nipple and areola. We performed a clinicopathologic analysis of cases of pregnancy-associated nipple hyperkeratosis. Observations: Twenty-five cases of pregnancy-associated nipple hyperkeratosis identified during a 5-year period (January 1, 2007, through December 31, 2012) are reported. The lesions were bilateral and involved predominantly the top of the nipple. Lesions were symptomatic in 17 patients (68%), causing tenderness or discomfort, pruritus, sensitivity to touch, and/or discomfort with breastfeeding. Nine patients (36%) experienced symptomatic aggravation only during pregnancy or breastfeeding. The lesions persisted post partum in 22 patients (88%). Histopathologic features were conspicuous orthokeratotic hyperkeratosis, with papillomatosis and acanthosis being mild or absent. Conclusions and Relevance: Pregnancy-associated hyperkeratosis of the nipple can be symptomatic and persist post partum. It may represent a physiologic change of pregnancy. The characteristic clinicopathologic features of this disorder allow differentiation from nevoid hyperkeratosis of the nipple and areola. We suggest that this distinctive clinicopathologic entity be called pregnancy-associated hyperkeratosis of the nipple. C1 [Higgins, H. William; Kroumpouzos, George] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Jenkins, Jennifer] Atrius Hlth, Dedham Med Associates, Div Dermatol, Dedham, MA USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Kroumpouzos, George] Atrius Hlth, South Shore Med Ctr, Norwell, MA USA. RP Kroumpouzos, G (reprint author), Rhode Isl Hosp, Dept Dermatol, APC 10,593 Eddy St, Providence, RI 02903 USA. EM gk@gkderm.com OI Kroumpouzos, George/0000-0002-5915-4640 NR 31 TC 4 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD JUN PY 2013 VL 149 IS 6 BP 722 EP 726 DI 10.1001/jamadermatol.2013.128 PG 5 WC Dermatology SC Dermatology GA 170MY UT WOS:000320857700011 PM 23616176 ER PT J AU Rogers, DJ Cunnane, MB Hartnick, CJ AF Rogers, Derek J. Cunnane, Mary Beth Hartnick, Christopher J. TI Vascular Compression of the Airway Establishing a Functional Diagnostic Algorithm SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID INNOMINATE-ARTERY COMPRESSION; SURGICAL-MANAGEMENT; COMPUTED-TOMOGRAPHY; ANOMALIES; CHILDREN; TRACHEA; ANESTHESIA; EXPOSURE; RISKS AB Importance: Pediatric imaging carries the risk of radiation exposure. Children frequently undergo computed tomography with angiography (CTA) for findings on bronchoscopy with limited knowledge regarding the necessity of such imaging. Objective: To report our experience with all pediatric patients at our institution over an 8-year period with airway symptoms warranting bronchoscopy followed by CTA for potential vascular anomaly. Goals were to report the percentage of positive findings seen on CTA leading to surgery; discuss relative radiation exposure risk and sedation risk for additional radio-logic studies; and propose a functional diagnostic algorithm. Design, Setting, and Participants: Retrospective chart review of 42 children aged 2 months to 11 years with tracheomalacia who underwent CTA between 2004 and 2012 in our tertiary aerodigestive center. Interventions: Bronchoscopy and CTA. Main Outcomes and Measures: Presence of vascular anomaly and need for thoracic surgery. Results: Of these 42 children, 21 (50%) had a vascular anomaly identified on CTA. Of these 21, 17 (81%) had innominate artery compression; 1 (5%) had double aortic arch; 1 (5%) had right aortic arch; 3 (14%) had bronchial compression by pulmonary artery; and 1 (5%) had dextrocardia with duplicated vena cava. Six (29%) of these 21 had clinical symptoms and CTA findings requiring thoracic surgery. The most common symptoms in children requiring thoracic surgery were cough, cyanosis, and stridor. Conclusions and Relevance: Deciding when to obtain imaging for bronchoscopic findings suggestive of vascular compression remains challenging. A diagnostic algorithm is proposed as a means to provide the best clinical care while weighing risks of additional radiation exposure vs sedation and exposure to general anesthesia. C1 [Rogers, Derek J.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, Boston, MA 02114 USA. [Cunnane, Mary Beth] Massachusetts Eye & Ear Infirm, Dept Pediat Neuroradiol, Boston, MA 02114 USA. [Cunnane, Mary Beth] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cunnane, Mary Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD JUN PY 2013 VL 139 IS 6 BP 586 EP 591 DI 10.1001/jamaoto.2013.3214 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 170MP UT WOS:000320856300006 PM 23787416 ER PT J AU Sabatini, ME Dizon, DS AF Sabatini, Mary E. Dizon, Don S. TI Why DOMA is unconstitutional, beyond the traditional views of same sex relationships SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Letter C1 [Sabatini, Mary E.] Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Vincent Mem Dept Obstet & Gynecol, Boston, MA 02114 USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Oncol Sexual Hlth Clin, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. RP Sabatini, ME (reprint author), Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Vincent Mem Dept Obstet & Gynecol, Boston, MA 02114 USA. EM msabatini@partners.org; ddizon@partners.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD JUN PY 2013 VL 30 IS 6 BP 861 EP 861 DI 10.1007/s10815-013-0020-3 PG 1 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 173EZ UT WOS:000321062200020 PM 23722937 ER PT J AU Guitton, TG Kinaci, A Ring, D AF Guitton, Thierry G. Kinaci, Ahmet Ring, David TI Diagnostic accuracy of 2-and 3-dimensional computed tomography and solid modeling of coronoid fractures SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Computed tomography; coronoid fracture; fracture classification; interobserver reliability; diagnostic performance characteristics ID PROXIMAL HUMERUS; RADIAL HEAD; ELBOW; DISLOCATION; RELIABILITY; CLASSIFICATION; AGREEMENT AB Purpose: This study measured the diagnostic performance characteristics and reliability of 2-dimensional (2DCT) and 3-dimensional (3DCT) computed tomography images and modeling of coronoid fractures. Method: The treating surgeon and first assistant evaluated 28 fractures for fracture type, specific characteristics, and proposed treatment. The observers evaluated the fractures 4 times: first based upon 2DCT computed images and radiographs; second with the addition of 3DCT images; third with the addition of 3D models; and finally based upon intra-operative exposure, which was considered the reference standard. Results: The diagnostic performance characteristics did not improve with more sophisticate imaging and models. The addition of 3DCT reconstructions improved the inter-observer reliability for fracture classification, characteristics, and proposed treatment. Conclusion: More sophisticated images and modeling improved reliability but not accuracy when characterizing coronoid fractures. Level of evidence: Level II, Diagnostic Study. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Guitton, Thierry G.; Kinaci, Ahmet; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 NR 23 TC 5 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUN PY 2013 VL 22 IS 6 BP 782 EP 786 DI 10.1016/j.jse.2013.02.009 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 172IP UT WOS:000320995800016 PM 23594717 ER PT J AU Reuben, DB Ganz, DA Roth, CP McCreath, HE Ramirez, KD Wenger, NS AF Reuben, David B. Ganz, David A. Roth, Carol P. McCreath, Heather E. Ramirez, Karina D. Wenger, Neil S. TI Effect of Nurse Practitioner Comanagement on the Care of Geriatric Conditions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality improvement; practice redesign; ACOVE; geriatric conditions ID RANDOMIZED-CONTROLLED-TRIAL; GUIDED CARE; COLLABORATIVE CARE; HEALTH-CARE; OLDER-PATIENTS; QUALITY; MANAGEMENT; INTERVENTION; ADULTS; DEPRESSION AB Objectives To determine whether community-based primary care physician (PCP)-nurse practitioner (NP) comanagement implementing the Assessing Care of Vulnerable Elders (ACOVE)-2 model: (case finding, delegation of data collection, structured visit notes, physician and patient education, and linkage to community resources) can improve the quality of care for geriatric conditions. Design Case study. Setting Two community-based primary care practices. Participants Patients aged 75 and older who screened positive for at least one condition: falls, urinary incontinence (UI), dementia, and depression. Intervention The ACOVE-2 model augmented by NP comanagement of conditions. Measurements Quality of care according to medical record review using ACOVE-3 quality indicators (QIs). Individuals receiving comanagement were compared with those who received PCP care alone in the same practices. Results Of 1,084 screened individuals, 658 (61%) screened positive for more than one condition; 485 of these were randomly selected for chart review and triggered a mean of seven QIs. A NP saw 49% for comanagement. Overall, individuals received 57% of recommended care. Quality scores for all conditions (falls, 80% vs 34%; UI, 66% vs 19%; dementia, 59% vs 38%) except depression (63% vs 60%) were higher for individuals who saw a NP. In analyses adjusted for sex and age of patient, number of conditions, site, and a NP estimate of medical management style, NP comanagement remained significantly associated with receiving recommended care (P<.001), as did NP estimate of medical management style (P=.02). Conclusion NP comanagement is associated with better quality of care for geriatric conditions in community-based primary care than usual care using the ACOVE-2 model. C1 [Reuben, David B.; Ganz, David A.; McCreath, Heather E.; Ramirez, Karina D.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. [Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA USA. [Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Ganz, David A.; Roth, Carol P.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA. [Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RP Reuben, DB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM dreuben@mednet.ucla.edu FU UniHealth Foundation; U.S. Department of Veterans Affairs, Veterans Health Administration, Veterans Affairs Health Services Research & Development Service (HSR&D) through the Veterans Affairs Greater Los Angeles HSR&D Center of Excellence [VA CD2 08-012-1]; National Institute on Aging [5P30AG028748] FX This project was supported by a grant from the UniHealth Foundation to DBR. DAG was supported by a Career Development Award from the U.S. Department of Veterans Affairs, Veterans Health Administration, Veterans Affairs Health Services Research & Development Service (HSR&D) through the Veterans Affairs Greater Los Angeles HSR&D Center of Excellence (Project VA CD2 08-012-1). Data collection and analysis was supported in part by the University of California at Los Angeles Claude Pepper Older Americans Independence Center funded by the National Institute on Aging (5P30AG028748). NR 23 TC 10 Z9 10 U1 7 U2 21 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 JUN PY 2013 VL 61 IS 6 BP 857 EP 867 DI 10.1111/jgs.12268 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 164KD UT WOS:000320407100001 PM 23772723 ER PT J AU Pawloski, PA Geiger, AM Haque, R Kamineni, A Fouayzi, H Ogarek, J Petersen, HV Bosco, JLF Thwin, SS Silliman, RA Field, TS AF Pawloski, Pamala A. Geiger, Ann M. Haque, Reina Kamineni, Aruna Fouayzi, Hassan Ogarek, Jessica Petersen, Hans V. Bosco, Jaclyn L. F. Thwin, Soe Soe Silliman, Rebecca A. Field, Terry S. TI Fracture Risk in Older, Long-Term Survivors of Early-Stage Breast Cancer SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE osteoporotic fractures; breast cancer survivors; postmenopausal women; cohort study; pharmacoepidemiology ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; INTERGROUP EXEMESTANE; SAFETY ANALYSIS; UNITED-STATES; TAMOXIFEN; CARE; TRIAL; OSTEOPOROSIS; MORTALITY AB Objectives To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors. Design A 10-year prospective cohort study beginning 5years after a diagnosis of breast cancer for survivors and match date for comparison women. Setting Six integrated healthcare systems. Participants Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer. Measurements Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk. Results No difference was observed in fracture rates between groups (hazard ratio (HR)=1.1, 95% confidence interval (CI)=0.9-1.3). The protective effect of tamoxifen was not statistically significant (HR=0.9, 95% CI=0.6-1.2). Conclusion Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use. C1 [Pawloski, Pamala A.] HealthPartners Inst Educ & Res, Minneapolis, MN USA. [Geiger, Ann M.] Wake Forest Sch Med, Winston Salem, NC USA. [Haque, Reina] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Kamineni, Aruna] Grp Hlth Res Inst, Seattle, WA USA. [Fouayzi, Hassan; Ogarek, Jessica; Field, Terry S.] Meyers Primary Care Inst, Worcester, MA USA. [Petersen, Hans V.] Lovelace Resp Res Inst, Albuquerque, NM USA. [Bosco, Jaclyn L. F.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. [Bosco, Jaclyn L. F.; Thwin, Soe Soe; Silliman, Rebecca A.] Boston Univ, Sch Med, Sect Geriatr, Boston Med Ctr, Boston, MA 02118 USA. [Thwin, Soe Soe] Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Pawloski, PA (reprint author), HealthPartners Inst Educ & Res, 8170 33rd Ave S,MS21111R, Bloomington, MN 55425 USA. EM pamala.a.pawloski@healthpartners.com FU Public Health Service from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [R01CA093772-05A2]; Novartis; International Serious Adverse Event Consortium; GlaxoSmithKline; Astra Zenica; Amgen; Pfizer; Merck; Sanofia Aventis FX Supported by Public Health Service Grant R01CA093772-05A2 (R Silliman, Principal Investigator) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. These findings were in part accepted for presentation at the 18th HMO Research Network Annual Conference, Seattle, Washington, May 2012.; The following conflicts of interest are reported for this study: receipt of salary for work performed on grants and contracts funded by commercial entities including Novartis and the International Serious Adverse Event Consortium (Pawloski); GlaxoSmithKline, Astra Zenica, Novartis, Amgen, Pfizer, Merck, Sanofia Aventis, and others (Petersen). NR 36 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2013 VL 61 IS 6 BP 888 EP 895 DI 10.1111/jgs.12269 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 164KD UT WOS:000320407100005 PM 23647433 ER PT J AU Espeland, MA Rejeski, WJ West, DS Bray, GA Clark, JM Peters, AL Chen, HY Johnson, KC Horton, ES Hazuda, HP AF Espeland, Mark A. Rejeski, W. Jack West, Delia S. Bray, George A. Clark, Jeanne M. Peters, Anne L. Chen, Haiying Johnson, Karen C. Horton, Edward S. Hazuda, Helen P. CA Action Hlth Diabet Res Grp TI Intensive Weight Loss Intervention in Older Individuals: Results from the Action for Health in Diabetes Type 2 Diabetes Mellitus Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE behavioral intervention; weight loss; physical activity; type 2 diabetes mellitus; cardiovascular disease risk factors ID LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; DISEASE RISK-FACTORS; LOOK-AHEAD TRIAL; CARDIOVASCULAR-DISEASE; KNEE OSTEOARTHRITIS; PHYSICAL-ACTIVITY; CLINICAL-TRIAL; ADULTS; OBESE AB Objectives To compare the effects of 4years of intensive lifestyle intervention on weight, fitness, and cardiovascular disease risk factors in older and younger individuals. Design Randomized controlled clinical trial. Setting Sixteen U.S. clinical sites. Participants Individuals with type 2 diabetes mellitus: 1,053 aged 65 to 76 and 4,092 aged 45 to 64. Interventions An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes mellitus support and education. Measurements Standardized assessments of weight, fitness (based on graded exercise testing), and cardiovascular disease risk factors. Results Over 4years, older individuals had greater intervention-related mean weight losses (6.2%) than younger participants (5.1%; interaction P=.006) and comparable relative mean increases in fitness (0.56 vs 0.53 metabolic equivalents; interaction P=.72). These benefits were seen consistently across subgroups of older adults formed according to many demographic and health factors. Of a panel of age-related health conditions, only self-reported worsening vision was associated with poorer intervention-related weight loss in older individuals. The intensive lifestyle intervention produced mean increases in high-density lipoprotein cholesterol (2.03mg/dL; P<.001) and decreases in glycated hemoglobin (0.21%; P<.001) and waist circumference (3.52cm; P<.001) over 4years that were at least as large in older as in younger individuals. Conclusion Intensive lifestyle intervention targeting weight loss and increased physical activity is effective in overweight and obese older individuals to produce sustained weight loss and improvements in fitness and cardiovascular risk factors. C1 [Espeland, Mark A.; Chen, Haiying] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC USA. [West, Delia S.] Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Clark, Jeanne M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Clark, Jeanne M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Peters, Anne L.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Espeland, MA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mespelan@wfubmc.edu OI Peters, Anne/0000-0003-0520-0776 FU National Institutes of Health; Department of Health and Human Services through the NIH [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Department of Veterans Affairs; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center; Massachusetts Institute of Technology General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center [M01RR000056]; Clinical Translational Research Center; Clinical and Translational Science Award [UL1 RR 024153]; NIH [DK 046204]; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX This work was funded under a cooperative agreement by the National Institutes of Health. The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.; This study is supported by the Department of Health and Human Services through the following cooperative agreements from the NIH: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; and Department of Veterans Affairs have contributed support. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service provided personnel, medical oversight, and use of facilities.; Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719), the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066), the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520), the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140), the University of Pittsburgh General Clinical Research Center (M01RR000056), the Clinical Translational Research Center funded by the Clinical and Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204), and the Frederic C. Bartter General Clinical Research Center (M01RR01346). NR 34 TC 16 Z9 18 U1 1 U2 15 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 JUN PY 2013 VL 61 IS 6 BP 912 EP 922 DI 10.1111/jgs.12271 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 164KD UT WOS:000320407100008 PM 23668423 ER PT J AU Hohman, MH Lee, LN Hadlock, TA AF Hohman, Marc H. Lee, Linda N. Hadlock, Tessa A. TI Two-Step Highly Selective Neurectomy for Refractory Periocular Synkinesis SO LARYNGOSCOPE LA English DT Editorial Material DE Facial paralysis; synkinesis; neurectomy; facial nerve ID BELLS-PALSY C1 [Hohman, Marc H.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Hohman, MH (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM marc_hohman@meei.harvard.edu NR 10 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2013 VL 123 IS 6 BP 1385 EP 1388 DI 10.1002/lary.23873 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 169MI UT WOS:000320784000013 PM 23315713 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Jens Skou-Nobel Prize in 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 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUN PY 2013 VL 88 IS 6 BP E55 EP E55 DI 10.1016/j.mayocp.2012.01.029 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 167TL UT WOS:000320657600002 PM 23726407 ER PT J AU Sung, CK Li, DW Andrews, E Drapkin, R Benjamin, T AF Sung, Chang K. Li, Dawei Andrews, Erik Drapkin, Ronny Benjamin, Thomas TI Promoter methylation of the SALL2 tumor suppressor gene in ovarian cancers SO MOLECULAR ONCOLOGY LA English DT Article DE SALL2; Ovarian cancer; Tumor suppressor; Promoter methylation; Polyoma T antigen ID RADIAL RAY SYNDROME; SV40-TRANSFORMED CELLS; CPG-ISLANDS; T-ANTIGEN; CARCINOMA; MUTATIONS; SURVIVAL; SPALT; GLYCOPROTEIN; P150(SAL2) AB The SALL2 gene product and transcription factor p150 were first identified in a search for tumor suppressors targeted for inactivation by the oncogenic mouse polyoma virus. SALL2 has also been identified as a cellular quiescence factor, essential for cells to enter and remain in a state of growth arrest under conditions of serum deprivation. p150 is a transcriptional activator of p21(Cip1/Waf1) and BAX, sharing important growth arrest and proapoptotic properties with p53. It also acts as a repressor of c-myc. Restoration of SALL2 expression in cells derived from a human ovarian carcinoma (OVCA) suppresses growth of the cells in immunodeficient mice. Here we examine the pattern of p150 expression in the normal human ovary, in OVCA-derived cell lines and in primary ovarian carcinomas. Immunohistochemical staining showed that p150 is highly expressed in surface epithelial cells of the normal human ovary. Expression is exclusively from the P2 promoter governing the E1A splice variant of p150. The P2 promoter is CpG-rich and susceptible to methylation silencing. p150 expression was restored in OVCA cell lines following growth in the presence of 5-azacytidine. In a survey of 210 cases of OVCA, roughly 90% across major and minor histological types failed to show expression of the protein. Immunological and biochemical approaches were used to show hypermethylation of the SALL2 P2 promoter in OVCA-derived cell lines and in a majority of primary tumors. These results bring together molecular biological and clinical evidence in support of a role of SALL2 as a suppressor of ovarian cancers. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Sung, Chang K.; Li, Dawei; Andrews, Erik; Benjamin, Thomas] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. [Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Benjamin, T (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, NRB-939,77 Ave Louis Pasteur, Boston, MA 02114 USA. EM thomas_benjamin@hms.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU National Cancer Institute [RO1 CA-092520]; Ovarian Cancer Research Fund; Mary Kay Foundation; Robert and Debra First Fund; Dana-Farber Women's Executive Council Genetic Fingerprinting Award; [P50 CA105009]; [U01 CA152990] FX This work has been supported by a grant from the National Cancer Institute RO1 CA-092520 to TB, grants P50 CA105009 and U01 CA152990, the Ovarian Cancer Research Fund, The Mary Kay Foundation, the Robert and Debra First Fund, and the Dana-Farber Women's Executive Council Genetic Finger-printing Award to RD. NR 52 TC 7 Z9 8 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 J9 MOL ONCOL JI Mol. Oncol. PD JUN PY 2013 VL 7 IS 3 BP 419 EP 427 DI 10.1016/j.molonc.2012.11.005 PG 9 WC Oncology SC Oncology GA 175LY UT WOS:000321233400011 PM 23273547 ER PT J AU Singh, A Lun, XQ Jayanthan, A Obaid, H Ruan, YB Strother, D Chi, SN Smith, A Forsyth, P Narendran, A AF Singh, Anjali Lun, Xueqing Jayanthan, Aarthi Obaid, Halah Ruan, Yibing Strother, Douglas Chi, Susan N. Smith, Amy Forsyth, Peter Narendran, Aru TI Profiling pathway-specific novel therapeutics in preclinical assessment for central nervous system atypical teratoid rhabdoid tumors (CNS ATRT): Favorable activity of targeting EGFR-ErbB2 signaling with lapatinib SO MOLECULAR ONCOLOGY LA English DT Article DE Lapatinib; Teratoid Rhabdoid tumors; Targeted therapeutics ID GROWTH-FACTOR RECEPTOR; KINASE INHIBITOR LAPATINIB; BREAST-CANCER CELLS; TERATOID/RHABDOID TUMOR; IN-VITRO; BRAIN-TUMORS; CYCLIN D1; FACTOR-II; INSULIN; MIGRATION AB Despite intensifying multimodal treatments, children with central nervous system atypical teratoid/rhabdoid tumor (CNS ATRT) continue to endure unacceptably high mortality rates. At present, concerted efforts are focusing on understanding the characteristic INI1 mutation and its implications for the growth and survival of these tumors. Additionally, pharmaceutical pipeline libraries constitute a significant source of potential agents that can be taken to clinical trials in a timely manner. However, this process requires efficient target validation and relevant preclinical studies. As an initial screening approach, a panel of 129 small molecule inhibitors from multiple pharmaceutical pipeline libraries was tested against three ATRT cell lines by in vitro cytotoxicity assays. Based on these data, agents that have strong activity and corresponding susceptible cellular pathways were identified. Target modulation, antibody array analysis, drug combination and in vivo xenograft studies were performed on one of the pathway inhibitors found in this screening. Approximately 20% of agents in the library showed activity with IC50 values of 1 mu M or less and many showed IC50 values less than 0.05 mu M. Intra cell line variability was also noted among some of the drugs. However, it was determined that agents capable of affecting pathways constituting ErbB2, mTOR, proteasomes, Hsp90, Polo like kinases and Aurora kinases were universally effective against the three ATRT cell lines. The first target selected for further analysis, the inhibition of ErbB2-EGFR pathway by the small molecule inhibitor lapatinib, indicated inhibition of cell migration properties and the initiation of apoptosis. Synergy between lapatinib and IGF-IR inhibition was also demonstrated by combination index (CI) values. Xenograft studies showed effective antitumor activity of lapatinib in vivo. We present an experimental approach to identifying agents and drug combinations for future clinical trials and provide evidence for the potential of lapatinib as an effective agent in the context of the biology and heterogeneity of its targets in ATRT. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Singh, Anjali; Lun, Xueqing; Jayanthan, Aarthi; Obaid, Halah; Ruan, Yibing; Chi, Susan N.; Smith, Amy; Narendran, Aru] Univ Calgary, POETIC, Lab Preclin & Drug Discovery Studies, Calgary, AB, Canada. [Strother, Douglas; Narendran, Aru] Alberta Childrens Prov Gen Hosp, Div Pediat Oncol & Transplant, Calgary, AB T3B 6A8, Canada. [Chi, Susan N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Amy] Arnold Palmer Hosp Children, MD Anderson Canc Ctr Orlando, Orlando, FL USA. [Forsyth, Peter] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Neurooncol, Tampa, FL 33682 USA. RP Narendran, A (reprint author), Alberta Childrens Prov Gen Hosp, Div Pediat Oncol, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM a.narendran@ucalgary.ca FU Kids Cancer Care Foundation of Alberta (KCCFA) Alberta Children's Hospital Foundation (ACHF); Brain Tumour Foundation of Canada; Canadian Institutes for Health Research (CIHR) Training Program in Genetics; Child Development and Health Graduate Studentship; Alberta Children's Hospital for Child and Maternal Health (ACHRI); McCarthy Tetrault Graduate Studentship; ACHF FX This research was supported by grants from the Kids Cancer Care Foundation of Alberta (KCCFA) Alberta Children's Hospital Foundation (ACHF) and the Brain Tumour Foundation of Canada. AJ holds a Canadian Institutes for Health Research (CIHR) Training Program in Genetics, Child Development and Health Graduate Studentship awarded by Alberta Children's Hospital for Child and Maternal Health (ACHRI) and a McCarthy Tetrault Graduate Studentship awarded by ACHF. NR 51 TC 11 Z9 11 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 J9 MOL ONCOL JI Mol. Oncol. PD JUN PY 2013 VL 7 IS 3 BP 497 EP 512 DI 10.1016/j.molonc.2013.01.001 PG 16 WC Oncology SC Oncology GA 175LY UT WOS:000321233400018 PM 23375777 ER PT J AU Middelbeek, RJW Chambers, MA Tantiwong, P Treebak, JT An, D Hirshman, MF Musi, N Goodyear, LJ AF Middelbeek, R. J. W. Chambers, M. A. Tantiwong, P. Treebak, J. T. An, D. Hirshman, M. F. Musi, N. Goodyear, L. J. TI Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle SO NUTRITION & DIABETES LA English DT Article DE obesity; insulin; diabetes; TBC1D1; AS160 ID TYPE-2 DIABETIC SUBJECTS; GLUT4 TRANSLOCATION; AKT SUBSTRATE; CONTRACTION; SENSITIVITY; OBESITY AB INTRODUCTION: Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal and cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 and TBC1D1 is critical for GLUT4 translocation facilitating glucose uptake, but their regulation in human skeletal muscle is not well understood. METHODS: Here, lean, obese and T2D subjects underwent a euglycemic-hyperinsulinemic clamp, and vastus lateralis muscle biopsies were obtained before, and at 30 and 180 min post insulin infusion. RESULTS: Obese and T2D subjects had higher body mass indexes and fasting insulin concentrations, and T2D subjects showed insulin resistance. Consistent with the clamp findings, T2D subjects had impaired insulin-stimulated phosphorylation of AS160 Thr(642), a site previously shown to be important in glucose uptake in rodents. Interestingly, insulin-stimulated phosphorylation of TBC1D1 Thr(590), a site shown to be regulated by insulin in rodents, was only increased in T2D subjects, although the functional significance of this difference is unknown. CONCLUSION: These data show that insulin differentially regulates AS160 and TBC1D1 phosphorylation in human skeletal muscle. Impaired insulin-stimulated glucose uptake in T2D subjects is accompanied by dysregulation of AS160 and TBC1D1 phosphorylation in skeletal muscle, suggesting that these proteins may regulate glucose uptake in humans. C1 [Middelbeek, R. J. W.; Chambers, M. A.; Treebak, J. T.; An, D.; Hirshman, M. F.; Goodyear, L. J.] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Tantiwong, P.; Musi, N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA. [Tantiwong, P.; Musi, N.] South Texas Vet Healthcare Syst, San Antonio, TX USA. [Goodyear, L. J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Goodyear, L. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Treebak, Jonas/B-4521-2017 OI Treebak, Jonas/0000-0003-1488-7012 FU National Institutes of Health [AR42238, K23-AG030979, RO1-DK80157, RO1-DK089229]; American Diabetes Association; VSBfonds Beurs; Scholten-Cordes Foundation; Haak Bastiaanse-Kuneman Foundation; NRSA [F32DK083183]; Danish Agency for Science, Technology and Innovation, Denmark FX This research was supported by the National Institutes of Health Grant AR42238 (to LJG). RJWM was supported by an American Diabetes Association mentor-based fellowship (to LJG), the VSBfonds Beurs, the Scholten-Cordes Foundation and the Haak Bastiaanse-Kuneman Foundation. MAC was supported by the NRSA grant F32DK083183. JTT was supported by a postdoctoral fellowship from The Danish Agency for Science, Technology and Innovation, Denmark. NM was supported by grants from the National Institutes of Health (K23-AG030979, RO1-DK80157 and RO1-DK089229) and the American Diabetes Association. Special thanks to Cell Signaling Technology (Danvers, MA, USA) for pan-TBC1D1 and TBC1D1 phospho-specific antibodies. This study was supported by the National Institutes of Health Grants AR42238 (to LJG) and K23-AG030979, RO1-DK80157, RO1-DK089229 and the American Diabetes Association (to NM). NR 20 TC 7 Z9 7 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-4052 J9 NUTR DIABETES JI Nutr. Diabetes PD JUN PY 2013 VL 3 AR UNSP e74 DI 10.1038/nutd.2013.13 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 171JO UT WOS:000320923000003 PM 23752133 ER PT J AU Hess, DR AF Hess, Dean R. TI Noninvasive Ventilation for Acute Respiratory Failure SO RESPIRATORY CARE LA English DT Article DE noninvasive ventilation; acute respiratory failure; COPD; acute cardiogenic pulmonary edema ID POSITIVE-PRESSURE VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; OBESITY HYPOVENTILATION SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; ACUTE LUNG INJURY; TOTAL FACE MASK; MECHANICAL VENTILATION; AIRWAY PRESSURE; SUPPORT VENTILATION AB Noninvasive ventilation (NW) for acute respiratory failure has gained much academic and clinical interest. Despite this, NIV is underutilized. The evidence strongly supports its use in patients presenting with an exacerbation of COPD and in patients with acute cardiogenic pulmonary edema. As reviewed in this paper, there is now evidence supporting or not supporting the use of NIV in various other presentations of acute respiratory failure. It is important not only to know when to initiate NIV, but also when this therapy is failing. Whether NW in the setting of acute respiratory failure can be managed appropriately outside the ICU setting is controversial. Although a variety of interfaces are available, the oronasal mask is the best initial interface in terms of leak prevention and patient comfort. Some critical care ventilators have NW modes that compensate well for leaks, but as a group the ventilators that are designed specifically for NW have better leak compensation. NW should be part of the armamentarium of all clinicians caring from patients with acute respiratory failure. (C) 2013 Daedalus Enterprises C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 187 TC 34 Z9 36 U1 0 U2 7 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 JUN PY 2013 VL 58 IS 6 BP 950 EP 969 DI 10.4187/respcare.02319 PG 20 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 164PV UT WOS:000320422900006 PM 23709194 ER PT J AU Mietto, C Pinciroli, R Patel, N Berra, L AF Mietto, Cristina Pinciroli, Riccardo Patel, Niti Berra, Lorenzo TI Ventilator Associated Pneumonia: Evolving Definitions and Preventive Strategies SO RESPIRATORY CARE LA English DT Article DE ventilator-associated pneumonia; VAP; nosocomial infections; mechanical ventilation; lung bacterial colonization; body positioning; endotracheal tube; modification; medical devices ID TRACHEAL TUBE CUFF; SUBGLOTTIC SECRETION DRAINAGE; COATED ENDOTRACHEAL-TUBES; REQUIRING MECHANICAL VENTILATION; INTENSIVE-CARE UNITS; RANDOMIZED-TRIAL; BACTERIAL-COLONIZATION; MUCUS SHAVER; SEMIRECUMBENT POSITION; CONTINUOUS ASPIRATION AB Ventilator-associated pneumonia (YAP) is one of the most frequent hospital-acquired infections occurring in intubated patients. Because YAP is associated with higher mortality, morbidity, and costs, there is a need to solicit further research for effective preventive measures. YAP has been proposed as an indicator of quality of care. Clinical diagnosis has been criticized to have poor accuracy and reliability. Thus, the Centers for Disease Control and Prevention has introduced a new definition based upon objective and recordable data. Institutions are nowadays reporting a YAP zero rate in surveillance programs, which is in discrepancy with clinical data. This reduction has been highlighted in epidemiological studies, but it can only be attributed to a difference in patient selection, since no additional intervention has been taken to modify pathogenic mechanisms in these studies. The principal determinant of YAP development is the presence of the endotracheal tube (ETT). Contaminated oropharyngeal secretions pool over the ETT cuff and subsequently leak down to the lungs through a hydrostatic gradient. Impairment of mucociliary motility and cough reflex cannot counterbalance with a proper clearance of secretions. Lastly, biofilm develops on the inner ETT surface and acts as a reservoir for microorganism inoculum to the lungs. New preventive strategies are focused on the improvement of secretions drainage and prevention of bacterial colonization. The influence of gravity on mucus flow and body positioning can facilitate the clearance of distal airways, with decreased colonization of the respiratory tract. A different approach proposes ETT modifications to limit the leakage of oropharyngeal secretions: subglottic secretion drainage and cuffs innovations have been addressed to reduce YAP incidence. Moreover, coated-ETTs have been shown to prevent biofilm formation, although there is evidence that ETT clearance devices (Mucus Shaver) are required to preserve the antimicrobial properties over time. Here, after reviewing the most noteworthy issues in YAP definition and pathophysiology, we will present the more interesting proposals for YAP prevention. (C) 2013 Daedalus Enterprises C1 [Mietto, Cristina; Pinciroli, Riccardo; Patel, Niti; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Medicine, Boston, MA 02114 USA. RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Medicine, 55 Fruit St, Boston, MA 02114 USA. EM lberra@partners.org NR 91 TC 33 Z9 38 U1 1 U2 18 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 JUN PY 2013 VL 58 IS 6 BP 990 EP 1003 DI 10.4187/respcare.02380 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 164PV UT WOS:000320422900010 PM 23709196 ER PT J AU Piriyapatsom, A Bittner, EA Hines, J Schmidt, UH AF Piriyapatsom, Annop Bittner, Edward A. Hines, Jessica Schmidt, Ulrich H. TI Sedation and Paralysis SO RESPIRATORY CARE LA English DT Article DE sedation; sedatives; critical illness; mechanical ventilation; neuromuscular blocking agent ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; RESPIRATORY-DISTRESS-SYNDROME; NEUROMUSCULAR BLOCKING-AGENTS; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SEDATION; ACUTE LUNG INJURY; CLINICAL-PRACTICE GUIDELINES; BREATHING CONTROLLED-TRIAL AB Sedation is used almost universally in the care of critically ill patients, especially in those who require mechanical ventilatory support or other life-saving invasive procedures. This review will focus on the sedation strategies for critically ill patients and the pharmacology of commonly used sedative agents. The role of neuromuscular blocking agents in the ICU will be examined and the pharmacology of commonly used agents is reviewed. Finally a strategy for rational use of these sedative and neuromuscular blocking agents in critically ill patients will be proposed. (C) 2013 Daedalus Enterprises C1 [Piriyapatsom, Annop; Bittner, Edward A.; Hines, Jessica; Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Schmidt, UH (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02115 USA. EM Uschinidt@partners.org NR 105 TC 2 Z9 2 U1 1 U2 4 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 JUN PY 2013 VL 58 IS 6 BP 1024 EP 1035 DI 10.4187/respcare.02232 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 164PV UT WOS:000320422900014 PM 23709198 ER PT J AU Kacmarek, RM AF Kacmarek, Robert M. TI Mechanical Ventilation Competencies of the Respiratory Therapist in 2015 and Beyond SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; manpower; education competencies; protocols ID HIGH-FREQUENCY OSCILLATION; INHALED NITRIC-OXIDE; DISTRESS-SYNDROME; PROTOCOLS; SUPPORT; ASSIST AB The evolution of critical care and mechanical ventilation has been dramatic and rapid over the last 10 years and can be expected to continue at this pace into the future. As a result, the competencies of the respiratory therapist regarding mechanical ventilation in 2015 and beyond are expected to also markedly increase. Respiratory therapists are expected to be the experts on the mechanical ventilator and all aspects of the application of mechanical ventilation. They will be considered consultants on all aspect of ventilatory support. This requires an expanded education in a number of areas. To achieve these levels of competency, as recommended by the third "2015 and Beyond" conference, the entry level education of the respiratory therapist of the future must be at the baccalaureate level. (C) 2013 Daedalus Enterprises C1 [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesiol, Cambridge, MA 02138 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 01460 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Warren 1225,55 Fruit St, Boston, MA 01460 USA. EM rkacmarek@partners.org NR 23 TC 5 Z9 5 U1 0 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 JUN PY 2013 VL 58 IS 6 BP 1087 EP 1092 DI 10.4187/respcare.02546 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 164PV UT WOS:000320422900022 PM 23709202 ER PT J AU Nurmi, EL Spilman, SL Whelan, F Scahill, LL Aman, MG McDougle, CJ Arnold, LE Handen, B Johnson, C Sukhodolsky, DG Posey, DJ Lecavalier, L Stigler, KA Ritz, L Tierney, E Vitiello, B McCracken, JT AF Nurmi, E. L. Spilman, S. L. Whelan, F. Scahill, L. L. Aman, M. G. McDougle, C. J. Arnold, L. E. Handen, B. Johnson, C. Sukhodolsky, D. G. Posey, D. J. Lecavalier, L. Stigler, K. A. Ritz, L. Tierney, E. Vitiello, B. McCracken, J. T. CA Res Units Pediat TI Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE autistic disorder; children; CNR1; leptin; risperidone; weight gain ID BODY-MASS INDEX; CB1 RECEPTOR ANTAGONIST; LEPTIN PROMOTER REGION; WHITE ADIPOSE-TISSUE; FOOD-INTAKE; HUMAN OBESITY; FTO GENE; ENDOCANNABINOID SYSTEM; SCHIZOPHRENIC-PATIENTS; LEPR POLYMORPHISMS AB Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N = 225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P = 1.0 x 10(-6)), CNR1 (P = 9.6 x 10(-5)) and the leptin (LEP) promoter (P = 1.4 x 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P = 1.3 x 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event. C1 [Nurmi, E. L.; Spilman, S. L.; Whelan, F.; McCracken, J. T.] UCLA Semel Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Scahill, L. L.; Sukhodolsky, D. G.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Aman, M. G.; Lecavalier, L.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [McDougle, C. J.] Massachusetts Gen Hosp, Dept Psychiat, Lurie Autism Ctr, Boston, MA 02114 USA. [Arnold, L. E.] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. [Handen, B.; Johnson, C.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Posey, D. J.; Stigler, K. A.] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. [Ritz, L.] NINDS, NIH, Bethesda, MD 20892 USA. [Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA. RP McCracken, JT (reprint author), UCLA Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM jmccracken@mednet.ucla.edu RI Nurmi, Erika/P-4627-2014; OI Nurmi, Erika/0000-0003-4893-8957; Sukhodolsky, Denis/0000-0002-5401-792X FU NIMH [T32MH073517, K23 MH094613, K24 MH010805, N01MH70010, N01MH80011, U10MH66768, N01MH70001, U10MH66766, N01MH70009, U10MH66764]; Korczak Foundation FX This work was partially supported by the following sources: NIMH grants T32MH073517 (ELN), K23 MH094613 (ELN), K24 MH010805 (JTM) and N01MH70010 (JTM), N01MH80011 and U10MH66768 (MGA), N01MH70001 and U10MH66766 (CJM), N01MH70009 and U10MH66764 (LLS) and a grant from the Korczak Foundation (LLS). Study medications were donated by Janssen Pharmaceutica. NR 87 TC 17 Z9 18 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JUN PY 2013 VL 3 AR e274 DI 10.1038/tp.2013.26 PG 8 WC Psychiatry SC Psychiatry GA 174VL UT WOS:000321184600008 PM 23799528 ER PT J AU Poelmans, G Franke, B Pauls, DL Glennon, JC Buitelaar, JK AF Poelmans, G. Franke, B. Pauls, D. L. Glennon, J. C. Buitelaar, J. K. TI AKAPs integrate genetic findings for autism spectrum disorders SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE A-kinase anchor proteins; autism spectrum disorders; genetics; genome-wide association studies ID DE-NOVO MUTATIONS; PROTEIN-KINASE-A; PERVASIVE DEVELOPMENTAL DISORDERS; COPY NUMBER VARIATION; LYMPHOBLASTOID CELL-LINES; MEDIAL PREFRONTAL CORTEX; CANDIDATE GENES; CLINICAL-IMPLICATIONS; REPETITIVE BEHAVIOR; EXPRESSION PROFILES AB Autism spectrum disorders (ASDs) are highly heritable, and six genome-wide association studies (GWASs) of ASDs have been published to date. In this study, we have integrated the findings from these GWASs with other genetic data to identify enriched genetic networks that are associated with ASDs. We conducted bioinformatics and systematic literature analyses of 200 top-ranked ASD candidate genes from five published GWASs. The sixth GWAS was used for replication and validation of our findings. Further corroborating evidence was obtained through rare genetic variant studies, that is, exome sequencing and copy number variation (CNV) studies, and/or other genetic evidence, including candidate gene association, microRNA and gene expression, gene function and genetic animal studies. We found three signaling networks regulating steroidogenesis, neurite outgrowth and (glutamatergic) synaptic function to be enriched in the data. Most genes from the five GWASs were also implicated-independent of gene size-in ASDs by at least one other line of genomic evidence. Importantly, A-kinase anchor proteins (AKAPs) functionally integrate signaling cascades within and between these networks. The three identified protein networks provide an important contribution to increasing our understanding of the molecular basis of ASDs. In addition, our results point towards the AKAPs as promising targets for developing novel ASD treatments. C1 [Poelmans, G.; Glennon, J. C.; Buitelaar, J. K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Poelmans, G.; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Pauls, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA USA. RP Poelmans, G (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, POB 9101,HP 204, NL-6500 HB Nijmegen, Netherlands. EM g.poelmans@donders.ru.nl RI Franke, Barbara/D-4836-2009 OI Franke, Barbara/0000-0003-4375-6572 FU European Community's Seventh Framework Programme [278948] FX The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no278948. We thank the families who made all the genetic studies of ASDs possible and the many investigators whose work drives the ASD genetics field forward. In particular, we are grateful to K Wang, H Hakonarson, LA Weiss and their collaborators for providing us with the detailed results from their GWASs. NR 108 TC 22 Z9 22 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JUN PY 2013 VL 3 AR e270 DI 10.1038/tp.2013.48 PG 11 WC Psychiatry SC Psychiatry GA 174VL UT WOS:000321184600004 PM 23756379 ER PT J AU Knobe, M Gradl, G AF Knobe, M. Gradl, G. TI Transplantation of Bone: Prerequisites for Immunologic and Inflammatory Conditions - an Overview SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA LA English DT Review ID GRAFT SUBSTITUTES; FRACTURE REPAIR; GROWTH-FACTORS; TNF-ALPHA; TGF-BETA; RESORPTION; OSTEOBLASTS; EXPRESSION; CYTOKINES; CELLS AB In this review we have summarized the conditions under which bone grafts have a suitable environment for ingrowth into surrounding bone. Among the topics discussed are the immunological properties of bone and differences between bone grafting and organ transplants. Local osteogenic immune changes following fracture and bone graft transplants are outlined. Moreover, techniques of bone graft harvesting are summarized. C1 [Knobe, M.; Gradl, G.] Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, D-52074 Aachen, Germany. [Gradl, G.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Gradl, G (reprint author), Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, Pauwelsstr 30, D-52074 Aachen, Germany. EM ggradl@ukaachen.de NR 47 TC 0 Z9 0 U1 0 U2 0 PU GALEN SRO PI PRAGUE 5 PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC SN 0001-5415 J9 ACTA CHIR ORTHOP TR JI Acta Chir. Orthop. Traumatol. Cechoslov. PD JUN PY 2013 VL 80 IS 3 BP 192 EP 196 PG 5 WC Orthopedics SC Orthopedics GA 175II UT WOS:000321223800002 PM 23777943 ER PT J AU Shah, K Quaas, J Rolston, D Bansal, S Bania, T Newman, D Wiener, D Lee, J AF Shah, Kaushal Quaas, Joshua Rolston, Daniel Bansal, Shalu Bania, Theodore Newman, David Wiener, Dan Lee, Jarone TI Magnitude of D-dimer matters for diagnosing pulmonary embolus SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID SIMPLE CLINICAL-MODEL; WHOLE-BLOOD ASSAY; COMPUTED-TOMOGRAPHY; EMERGENCY-DEPARTMENT; PRETEST PROBABILITY; WORK-UP; MANAGEMENT; ANGIOGRAPHY; THRESHOLD; INCREASE AB Objective: The objective of this study is to determine whether the magnitude of the D-dimer correlates with a higher likelihood of pulmonary embolus (PE). Methods: We performed an electronic chart review at our academic, tertiary care center, annual emergency department (ED) census greater than 100000. All patients with a chest computed tomographic (CT) scan with intravenous contrast and an elevated D-dimer level obtained in the ED between January 2001 and July 2008 were identified. Specific, predetermined, predefined data elements including sex, age, D-dimer level, and final ED diagnosis were recorded by a hypothesis-blinded extractor using a preformatted data form. D-dimer level less than 0.58 mu g/mL constitutes the normal laboratory reference range for our turbidometric D-dimer assay. Data were analyzed using standard statistical methods, and a linear regression analysis was performed for correlation analysis of D-dimer and diagnosis of PE. Results: We identified 544 subjects who had both a chest CT scan performed and an elevated D-dimer level obtained in the ED. Fifty-eight subjects (10.7%; mean D-dimer, 4.9 mu g/mL) were diagnosed with PE, and 486 (89.3%; mean D-dimer, 2.0) did not have a PE. The percentages of PE diagnoses for D-dimers in the ranges 0.58 to 1.0, 1.0 to 2.0, 2.0 to 5.0, 5.0 to 20.0, and greater than 20.0 (n=11) were 3.6%, 8.0%, 16.2%, 35.3%, and 45.5%, respectively. The positive predictive value of PE for D-dimer level cutoffs of greater than 0.58, greater than 1.0, greater than 2.0, greater than 5.0, and greater than 20.0 was 10.7%, 14.6%, 22.2%, 37.8%, and 45.5%, respectively. Increasing D-dimer values were strongly correlated with the presence of PE (odds ratio, 1.1685 per stratum; P < .001). Conclusion: Increasing magnitude of D-dimer correlates with increasing likelihood of PE diagnosed by CT angiography. (C) 2013 Elsevier Inc. All rights reserved. C1 [Shah, Kaushal; Newman, David] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Quaas, Joshua; Rolston, Daniel; Bania, Theodore; Wiener, Dan] St Lukes Roosevelt Hosp, Dept Emergency Med, New York, NY 10025 USA. [Bansal, Shalu] Mayo Clin & Mayo Grad Sch Med, Rochester, MN 55905 USA. [Lee, Jarone] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM lee.jarone@mgh.harvard.edu OI Rolston, Daniel/0000-0001-7595-2418; Lee, Jarone/0000-0002-4532-8523 NR 32 TC 4 Z9 5 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUN PY 2013 VL 31 IS 6 BP 942 EP 945 DI 10.1016/j.ajem.2013.03.009 PG 4 WC Emergency Medicine SC Emergency Medicine GA 167SO UT WOS:000320655100009 PM 23685058 ER PT J AU Lee, DC Peak, DA Jones, JS Domeier, RM Hendry, PL Rathlev, NK Swor, RA McLean, SA AF Lee, David C. Peak, David A. Jones, Jeffrey S. Domeier, Robert M. Hendry, Phyllis L. Rathlev, Niels K. Swor, Robert A. McLean, Samuel A. TI Variations in institutional review board reviews of a multi-center, Emergency Department (ED)-based genetic research protocol SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RESPONSES; STANDARD AB Introduction: In the United States, institutional review boards (IRBs) oversee the scientific, ethical, and regulatory aspects of research conducted on human subjects. Institutional variations in the interpretation and application of federal and local regulations concerning genetic testing can have significant impact on the implementation of such studies. Objective: We assessed variability in IRB review of a multi-center Emergency Department-based study examining genotypic and phenotypic predictors of pain and psychological outcomes after minor motor vehicle collision (Project CRASH). This is one of the first multi-center genetic research protocols based solely in the Emergency Department (ED). Methods: We performed an observational study of sites participating in Project CRASH. We collected IRB information and correspondence from each site. We collected data that included information regarding institution demographics, original IRB application characteristics, subsequent IRB correspondence, and time interval between submission and approval. Descriptive statistics were used in analysis. Results: All sites that initially agreed to participate in Project CRASH also participated in this study (n = 7). The time interval in receiving IRB approval varied between 20-760 days (median 105, IQR 21-225). One site appeared to be an outlier (760 days). The most commonly requested changes were changes to the consent form. Conclusion: Institutional interpretation of regulations regarding our ED-based genetic study was highly variable. Although the majority of our results are consistent with other similar published studies, the mean time interval for approval for this genetic study is far greater than other reported studies. (C) 2013 Elsevier Inc. All rights reserved. C1 [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY 11030 USA. [Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jones, Jeffrey S.] Spectrum Hlth, Dept Emergency Med, Grand Rapids, MI 49503 USA. [Domeier, Robert M.] St Joseph Mercy Hosp, Dept Emergency Med, Ann Arbor, MI 48197 USA. [Hendry, Phyllis L.] Univ Florida, Dept Emergency Med & Pediat, Jacksonville, FL 32608 USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA 01199 USA. [Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48073 USA. [McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA. RP Lee, DC (reprint author), N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY 11030 USA. EM dlee@nshs.edu OI McLean, Samuel/0000-0001-9482-3582 FU NIAMS NIH HHS [R01 AR056328] NR 5 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUN PY 2013 VL 31 IS 6 BP 967 EP 969 DI 10.1016/j.ajem.2013.03.003 PG 3 WC Emergency Medicine SC Emergency Medicine GA 167SO UT WOS:000320655100015 PM 23623236 ER PT J AU Carr, CE Rowedder, H Lui, CS Zlatkovsky, I Papalias, CW Bolander, J Myers, JW Bustillo, J Rothberg, JM Zuber, MT Ruvkun, G AF Carr, Christopher E. Rowedder, Holli Lui, Clarissa S. Zlatkovsky, Ilya Papalias, Chris W. Bolander, Jarie Myers, Jason W. Bustillo, James Rothberg, Jonathan M. Zuber, Maria T. Ruvkun, Gary TI Radiation Resistance of Sequencing Chips for in situ Life Detection SO ASTROBIOLOGY LA English DT Article DE Laboratory simulation experiments; Life-detection instruments; Nucleic acids; Mars; Panspermia ID BURROWS-WHEELER TRANSFORM; MURCHISON METEORITE; SUBSURFACE OCEAN; EXTRATERRESTRIAL NUCLEOBASES; CARBONACEOUS METEORITES; READ ALIGNMENT; MARS; ENCELADUS; PLANETS; SIMULATION AB Life beyond Earth may be based on RNA or DNA if such life is related to life on Earth through shared ancestry due to meteoritic exchange, such as may be the case for Mars, or if delivery of similar building blocks to habitable environments has biased the evolution of life toward utilizing nucleic acids. In this case, in situ sequencing is a powerful approach to identify and characterize such life without the limitations or expense of returning samples to Earth, and can monitor forward contamination. A new semiconductor sequencing technology based on sensing hydrogen ions released during nucleotide incorporation can enable massively parallel sequencing in a small, robust, optics-free CMOS chip format. We demonstrate that these sequencing chips survive several analogues of space radiation at doses consistent with a 2-year Mars mission, including protons with solar particle event-distributed energy levels and 1 GeV oxygen and iron ions. We find no measurable impact of irradiation at 1 and 5 Gy doses on sequencing quality nor on low-level hardware characteristics. Further testing is required to study the impacts of soft errors as well as to characterize performance under neutron and gamma irradiation and at higher doses, which would be expected during operation in environments with significant trapped energetic particles such as during a mission to Europa. Our results support future efforts to use in situ sequencing to test theories of panspermia and/or whether life has a common chemical basis. C1 [Carr, Christopher E.; Lui, Clarissa S.; Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA USA. [Carr, Christopher E.; Rowedder, Holli; Lui, Clarissa S.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Carr, Christopher E.; Rowedder, Holli; Lui, Clarissa S.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Zlatkovsky, Ilya; Papalias, Chris W.; Bolander, Jarie; Myers, Jason W.; Bustillo, James; Rothberg, Jonathan M.] Life Technol, San Francisco, CA USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,185 Cambridge St,CPZN 7250, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU NASA's ASTID program [NNX08AX15G] FX We thank Peter Guida, Adam Rusek, and the rest of the NSRL-associated staff for assistance with the irradiations, and Alan Natapoff at MIT for statistical advice. This work was funded by NASA's ASTID program (NNX08AX15G). NR 37 TC 1 Z9 1 U1 4 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1531-1074 J9 ASTROBIOLOGY JI Astrobiology PD JUN PY 2013 VL 13 IS 6 BP 560 EP 569 DI 10.1089/ast.2012.0923 PG 10 WC Astronomy & Astrophysics; Biology; Geosciences, Multidisciplinary SC Astronomy & Astrophysics; Life Sciences & Biomedicine - Other Topics; Geology GA 168LO UT WOS:000320707500006 PM 23734755 ER PT J AU Klosky, JL Hum, AM Zhang, N Ali, KS Srivastava, DK Klesges, RC Emmons, KM Ness, KK Stovall, M Robison, LL Hudson, MM AF Klosky, James L. Hum, Ashley M. Zhang, Nan Ali, Khatidja S. Srivastava, D. Kumar Klesges, Robert C. Emmons, Karen M. Ness, Kirsten K. Stovall, Marilyn Robison, Leslie L. Hudson, Melissa M. TI Smokeless and Dual Tobacco Use Among Males Surviving Childhood Cancer: A Report From the Childhood Cancer Survivor Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SMOKING-CESSATION; ADULT SURVIVORS AB Cancer survivors experience treatment-related complications that can be exacerbated by tobacco use. This study reports the prevalence of smokeless and dual tobacco use, compares these rates to the U. S. population, and examines tobacco risk factors among males surviving childhood cancer. Data from the Childhood Cancer Survivor Study (CCSS) 2007 survey were used (N 3378). Standardized incidence ratios (SIR) were obtained by comparing CCSS data with the National Survey on Drug Use and Health. Logistic regression was used to evaluate associations between risk factors and tobacco use. Amongmale survivors, 8.3% and 2.3% were current smokeless tobacco and dual tobacco users, respectively. Survivors were less likely than population males to report smokeless tobacco [SIR=0.64; 95% confidence interval (CI), 0.57-0.72) or dual tobacco (SIR=0.37; CI, 0.29-0.46) use; however, non-White survivors aged 35 to 49 years were more likely to use smokeless tobacco (SIR=2.32; CI, 1.27-3.90). Smokeless tobacco use was associated (P < 0.05) with younger age at diagnosis, lower education, being married or divorced/separated, and not living in the Northeastern United State, whereas history of cardiovascular-and/or pulmonary-toxic treatment was protective. Dual tobacco use was associated with younger age at diagnosis, lower education, divorce/separation, and high psychologic distress. Having active heart or circulatory conditions was protective. Although smokeless tobacco/dual tobacco use is generally low among childhood cancer survivors, these findings suggest that tobacco use screening should be expanded to include smokeless tobacco use, and that smokeless tobacco-specific education and cessation interventions should be provided to users. Screening and intervening for smokeless tobacco/dual tobacco use in childhood cancer survivors will reduce tobacco-related morbidity and mortality. (C) 2013 AACR. C1 [Klosky, James L.; Hum, Ashley M.; Ali, Khatidja S.] St Jude Childrens Res Hosp, Dept Psychol, Memphis, TN 38105 USA. [Zhang, Nan; Srivastava, D. Kumar] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Klesges, Robert C.; Ness, Kirsten K.; Robison, Leslie L.; Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Klesges, Robert C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Klosky, JL (reprint author), St Jude Childrens Res Hosp, Dept Psychol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM james.klosky@stjude.org OI Clawson, Ashley/0000-0003-4290-5310 FU National Cancer Institute [CA55727]; NIH Cancer Support (CORE) grant; American Lebanese Syrian Associated Charities FX This work was supported by National Cancer Institute grant CA55727 (to L. L. Robison, Principal Investigator), NIH Cancer Support (CORE) grant (to R. Gilbertson, Principal Investigator), and the American Lebanese Syrian Associated Charities. NR 25 TC 2 Z9 2 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2013 VL 22 IS 6 BP 1025 EP 1029 DI 10.1158/1055-9965.EPI-12-1302 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 167PF UT WOS:000320643200003 PM 23580700 ER PT J AU Yamauchi, M Lochhead, P Imamura, Y Kuchiba, A Liao, XY Qian, ZR Nishihara, R Morikawa, T Shima, K Wu, KN Giovannucci, E Meyerhardt, JA Fuchs, CS Chan, AT Ogino, S AF Yamauchi, Mai Lochhead, Paul Imamura, Yu Kuchiba, Aya Liao, Xiaoyun Qian, Zhi Rong Nishihara, Reiko Morikawa, Teppei Shima, Kaori Wu, Kana Giovannucci, Edward Meyerhardt, Jeffrey A. Fuchs, Charles S. Chan, Andrew T. Ogino, Shuji TI Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with Colorectal Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; OF-THE-LITERATURE; III COLON-CANCER; MICROSATELLITE INSTABILITY; ACTIVITY QUESTIONNAIRE; PERSONALIZED MEDICINE; SIGNALING PATHWAY; MODERATE EXERCISE AB Background: Higher levels of physical activity are associated with lower colorectal carcinoma incidence and mortality, perhaps through influencing energy balance, cellular prosta7 systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for COX-2) status on clinical outcome remain unknown. Methods: Using molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to postdiagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality HR, adjusting for clinical and other tumor variables including microsatellite instability status. Results: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (P-trend = 0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (P-trend = 0.84; P-interaction = 0.024, between physical activity and tumor PTGS2 status). Conclusions: Postdiagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors but not among patients with PTGS2-negative tumors. Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise. (c) 2013 AACR. C1 [Yamauchi, Mai; Lochhead, Paul; Imamura, Yu; Kuchiba, Aya; Liao, Xiaoyun; Qian, Zhi Rong; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yamauchi, Mai; Lochhead, Paul; Imamura, Yu; Kuchiba, Aya; Liao, Xiaoyun; Qian, Zhi Rong; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lochhead, Paul] Univ Aberdeen, Gastrointestinal Res Grp, Inst Med Sci, Aberdeen, Scotland. [Kuchiba, Aya; Nishihara, Reiko; Wu, Kana; Giovannucci, Edward] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02114 USA. [Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02114 USA. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan. [Shima, Kaori] Kagoshima Univ, Dept Oral Pathol, Kagoshima 890, Japan. [Giovannucci, Edward; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Div Gastroenterol,Channing Div Network Med,Med Sc, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org; shuji_ogino@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU NIH [P01 CA87969, P01 CA55075, 1UM1 CA167552, P50 CA127003, R01 CA151993, R01 CA137178]; Harvard University Knox Memorial Fellowship FX This work was supported by NIH grants [P01 CA87969 (to S.E. Hankinson), P01 CA55075 (to W.C. Willett), 1UM1 CA167552 (to W.C. Willett), P50 CA127003 (to C.S. Fuchs), R01 CA151993 (to S. Ogino), and R01 CA137178 (to A.T. Chan)]. P. Lochhead is a Scottish Government Clinical Academic Fellow and was supported by a Harvard University Knox Memorial Fellowship. A.T. Chan is a Damon Runyon Cancer Foundation Clinical Investigator. NR 89 TC 17 Z9 17 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2013 VL 22 IS 6 BP 1142 EP 1152 DI 10.1158/1055-9965.EPI-13-0108 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 167PF UT WOS:000320643200018 PM 23629521 ER PT J AU Valente, AM Lakdawala, NK Powell, AJ Evans, SP Cirino, AL Orav, EJ MacRae, CA Colan, SD Ho, CY AF Valente, Anne Marie Lakdawala, Neal K. Powell, Andrew J. Evans, Sarah P. Cirino, Allison L. Orav, E. John. MacRae, Calum A. Colan, Steven D. Ho, Carolyn Y. TI Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular Hypertrophy SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE cardiac MRI; cardiomyopathy, hypertrophic; echocardiography; genetics; humans ID LATE GADOLINIUM ENHANCEMENT; DILATED CARDIOMYOPATHY; HEART-ASSOCIATION; OF-CARDIOLOGY; ABNORMALITIES; PHENOTYPE; GUIDELINES; DIAGNOSIS; COMMITTEE; FAMILIES AB Background- Left ventricular hypertrophy (LVH) typically manifests during or after adolescence in sarcomere mutation carriers at risk for developing hypertrophic cardiomyopathy. Guidelines recommend serial imaging of mutation carriers without LVH (G+/LVH-) to monitor for phenotypic evolution, but the optimal strategy is undefined. Compared with echocardiography (echo), cardiac MRI (CMR) offers improved endocardial visualization and potential to assess scar. However, the incremental advantage offered by CMR for early diagnosis of hypertrophic cardiomyopathy is unclear. Therefore, we systematically compared echo and CMR in G+/LVH- subjects. Methods and Results- A total of 40 sarcomere mutation carriers with normal echo wall thickness (<12 mm or z score <2.5 in children) underwent concurrent CMR. Mean age was 21.7 +/- 11.1 years, 55% were female. If left ventricular wall thickness seemed nonuniform, the size and location of relatively thickened segments were noted. Late gadolinium enhancement was assessed with CMR. Diagnostic agreement between echo and CMR was good (90%), although CMR measurements of left ventricular wall thickness were approximate to 19% lower than echo. Four subjects had mild hypertrophy (12.6-14 mm; <= 2 segments) appreciated by CMR but not echo. No subjects had late gadolinium enhancement. During median 35-month follow-up, 2 subjects developed overt hypertrophic cardiomyopathy, including 1 with mild LVH by CMR at baseline. Conclusions- Echo is unlikely to miss substantial LVH; however, CMR identified mild hypertrophy in approximate to 10% of mutation carriers with normal echo wall thickness. CMR may be a useful adjunct in hypertrophic cardiomyopathy family screening, particularly in higher risk situations, or if echocardiographic images are suboptimal or suggest borderline LVH. C1 [Valente, Anne Marie; Lakdawala, Neal K.; Cirino, Allison L.; MacRae, Calum A.; Ho, Carolyn Y.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Valente, Anne Marie; Powell, Andrew J.; Evans, Sarah P.; Colan, Steven D.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Orav, E. John.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Lakdawala, Neal K.] VA Boston Healthcare Syst, Boston, MA USA. RP Ho, CY (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM cho@partners.org OI Ho, Carolyn/0000-0002-7334-7924 FU National Heart, Lung, and Blood Institute at the National Institutes of Health [5K23HL078901, 1P20HL101408] FX This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [5K23HL078901 and 1P20HL101408 to C.Y. Ho]. NR 33 TC 13 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2013 VL 6 IS 3 BP 230 EP 237 DI 10.1161/CIRCGENETICS.113.000037 PG 8 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 166TL UT WOS:000320580700003 PM 23690394 ER PT J AU Hedrich, CM Tsokos, GC AF Hedrich, Christian M. Tsokos, George C. TI Bridging the gap between autoinflammation and autoimmunity SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID EXONUCLEASE TREX1; IL-10 EXPRESSION; MUTATIONS; DISEASE; GENE; DNA C1 [Hedrich, Christian M.; Tsokos, George C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Rheumatol, Dept Med,Med Sch, Boston, MA 02215 USA. RP Hedrich, CM (reprint author), Beth Israel Deaconess Med Ctr CLS 937, Div Rheumatol, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA. EM chedrich@bidmc.harvard.edu NR 28 TC 3 Z9 3 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2013 VL 147 IS 3 SI SI BP 151 EP 154 DI 10.1016/j.clim.2013.03.006 PG 4 WC Immunology SC Immunology GA 168EO UT WOS:000320688700001 PM 23587745 ER PT J AU Luo, S Cha, JS Wilke, C Breen, C Zhou, LDH AF Luo, Su Cha, Jisun Wilke, Caroline Breen, Catherine Zhou, Linda Hua TI What Is Your Diagnosis? Primary Localized Cutaneous Nodular Amyloidosis SO CUTIS LA English DT Editorial Material ID OF-THE-LITERATURE; TERM-FOLLOW-UP; EXCISION C1 [Luo, Su; Cha, Jisun; Wilke, Caroline; Breen, Catherine; Zhou, Linda Hua] Roger Williams Med Ctr, Providence, RI 02908 USA. [Luo, Su; Cha, Jisun; Zhou, Linda Hua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol & Skin Surg, Boston, MA USA. [Wilke, Caroline; Breen, Catherine] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zhou, LDH (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, 50 Maude St, Providence, RI 02908 USA. EM lindahuazhou@yahoo.com NR 19 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2013 VL 91 IS 6 BP 271 EP + PG 3 WC Dermatology SC Dermatology GA 166PL UT WOS:000320569400002 PM 23837156 ER PT J AU Matsumoto, AM AF Matsumoto, Alvin M. TI Testosterone Administration in Older Men SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Hypogonadism; Aging; Diagnosis; Testosterone; Treatment ID CLINICAL-PRACTICE GUIDELINE; SEX-HORMONE LEVELS; SERUM TESTOSTERONE; ANDROGEN DEFICIENCY; ELDERLY-MEN; HYPOGONADAL MEN; HEALTHY-YOUNG; ADULT MEN; PROSTATE; THERAPY AB The only indication for testosterone administration in older men is testosterone replacement therapy for male hypogonadism. Compared with young hypogonadal men, the diagnosis and management of male hypogonadism in older men is more challenging. Both the clinical manifestations of androgen deficiency and low testosterone levels may be caused or modified by comorbid illnesses that occur and medications taken more frequently by older men, resulting in a greater likelihood for overdiagnosis of hypogonadism and subsequent inappropriate use of and inadequate response to testosterone treatment. It is important to use a systematic, holistic approach to the diagnosis and management of older men with hypogonadism. C1 [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Clin Res Unit, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Matsumoto, AM (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 South Columbian Way S-182-GRECC, Seattle, WA 98108 USA. EM alvin.matsumoto@va.gov NR 32 TC 7 Z9 8 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 2013 VL 42 IS 2 BP 271 EP + DI 10.1016/j.ecl.2013.02.011 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 168XK UT WOS:000320741000007 PM 23702401 ER PT J AU Rozman, PA Eskandar, E Madsen, JR Thesen, T Carlson, C Devinsky, O Kuzniecky, R Doyle, WK Ulbert, I Halgren, E Cash, SS AF Rozman, P. A. Eskandar, E. Madsen, J. R. Thesen, T. Carlson, C. Devinsky, O. Kuzniecky, R. Doyle, W. K. Ulbert, I Halgren, E. Cash, S. S. TI MULTI-UNIT ACTIVITY IN THE HUMAN NEOCORTEX AS A PREDICTOR OF SEIZURE ONSET SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Rozman, P. A.; Cash, S. S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rozman, P. A.; Eskandar, E.; Cash, S. S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Eskandar, E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Madsen, J. R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Madsen, J. R.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Thesen, T.; Carlson, C.; Devinsky, O.; Kuzniecky, R.; Doyle, W. K.] NYU, Med Ctr, Comprehens Epilepsy Ctr, New York, MA USA. [Ulbert, I] Natl Inst Neurosci, Budapest, Hungary. [Ulbert, I] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Ulbert, I] Peter Pazmany Catholic Univ, Dept Informat Technol, Budapest, Hungary. [Halgren, E.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Halgren, E.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Halgren, E.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 9 EP 10 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472000019 ER PT J AU Moura, LMVR Almeida, KT Bezerra, MP Kilbride, RD AF Moura, L. M. V. R. Almeida, K. T. Bezerra, M. P. Kilbride, R. D. TI TIME TO SPECIALIST EPILEPSY EVALUATION AND ITS RELATION TO SEIZURE CONTROL SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Moura, L. M. V. R.; Kilbride, R. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA. [Almeida, K. T.; Bezerra, M. P.] Univ Estado Rio De Janeiro, Hosp Univ Pedro Ernesto, Dept Neurol, Rio De Janeiro, Brazil. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 57 EP 57 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472000165 ER PT J AU Moura, LMVR Almeida, KT Kilbride, RD Cole, AJ Hoch, DB AF Moura, L. M. V. R. Almeida, K. T. Kilbride, R. D. Cole, A. J. Hoch, D. B. TI ADHERENCE TO EPILEPSY QUALITY INDICATORS IN SPECIALIZED EPILEPSY CARE CENTERS: A COMPARISON BETWEEN DISPARATE HEALTH CARE SYSTEMS SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Moura, L. M. V. R.; Kilbride, R. D.; Cole, A. J.; Hoch, D. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA. [Almeida, K. T.] Univ Estado Rio De Janeiro, Hosp Univ Pedro Ernesto, Dept Neurol, Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 58 EP 58 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472000166 ER PT J AU Almeida, KT Moura, LMVR Bezerra, MP Kilbride, RD AF Almeida, K. T. Moura, L. M. V. R. Bezerra, M. P. Kilbride, R. D. TI AVAILABILITY OF THE NEWER GENERATION OF ANTI-EPILEPTIC DRUGS IN TWO TERTIARY REFERRAL EPILEPSY CENTERS SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Almeida, K. T.; Bezerra, M. P.] Univ Estado Rio de Janeiro, Hosp Univ Pedro Ernesto, Dept Neurol, BR-20550011 Rio De Janeiro, Brazil. [Moura, L. M. V. R.; Kilbride, R. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 59 EP 59 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472000171 ER PT J AU Gill, SN Duron, RM Medina, MT Martinez-Juarez, I Alonso, MA Ochoa, A Jara-Prado, A Machado-Salas, J Tanaka, M Bailey, JN Delgado-Escueta, A AF Gill, S. N. Duron, R. M. Medina, M. T. Martinez-Juarez, I Alonso, M. A. Ochoa, A. Jara-Prado, A. Machado-Salas, J. Tanaka, M. Bailey, J. N. Delgado-Escueta, A. TI FOCAL SPIKES IN ASYMPTOMATIC MEMBERS OF JUVENILE MYOCLONIC EPILEPSY FAMILIES WITH MUTATED EPILEPSY GENES SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Gill, S. N.; Tanaka, M.; Delgado-Escueta, A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gill, S. N.; Duron, R. M.; Tanaka, M.; Bailey, J. N.; Delgado-Escueta, A.] VA Greater Los Angeles Healthcare Syst, Neurol Serv, Epilepsy Genet Genom Lab, Los Angeles, CA USA. [Gill, S. N.; Duron, R. M.; Tanaka, M.; Bailey, J. N.; Delgado-Escueta, A.] VA Greater Los Angeles Healthcare Syst, Res Serv, Epilepsy Genet Genom Lab, Los Angeles, CA USA. [Gill, S. N.; Duron, R. M.; Medina, M. T.; Martinez-Juarez, I; Alonso, M. A.; Ochoa, A.; Jara-Prado, A.; Machado-Salas, J.; Tanaka, M.; Bailey, J. N.; Delgado-Escueta, A.] Int GENESS Consortium, Los Angeles, CA USA. [Duron, R. M.] Lucas Med Ctr, Dept Neurol, Tegucigalpa, Honduras. [Duron, R. M.; Medina, M. T.] Natl Autonomous Univ, Dept Neurol, Tegucigalpa, Honduras. [Martinez-Juarez, I; Alonso, M. A.; Ochoa, A.; Jara-Prado, A.] Natl Inst Neurol & Neurosurg, Dept Neurol, Mexico City, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 194 EP 194 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472000616 ER PT J AU Ng, MC Kilbride, R Simon, MV Eskandar, E Cole, AJ AF Ng, M. C. Kilbride, R. Simon, M., V Eskandar, E. Cole, A. J. TI HIPPOCAMPOGRAPHY AND HIPPOCAMPECTOMY IN DOMINANT LESIONAL EXTRAHIPPOCAMPAL TEMPORAL LOBE EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Ng, M. C.; Kilbride, R.; Simon, M., V; Eskandar, E.; Cole, A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 265 EP 265 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472001140 ER PT J AU Mosher, JC Hamalainen, MS Nair, DR Alexopoulos, AV Burgess, RC So, NK Najm, IM AF Mosher, J. C. Haemaelaeinen, M. S. Nair, D. R. Alexopoulos, A., V Burgess, R. C. So, N. K. Najm, I. M. TI WIDE-BAND DETECTION AND LOCALIZATION OF NORMAL HIGH FREQUENCY OSCILLATIONS IN EVOKED RESPONSE MAGNETIC FIELDS SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Mosher, J. C.; Nair, D. R.; Alexopoulos, A., V; Burgess, R. C.; So, N. K.; Najm, I. M.] Cleveland Clin, Epilepsy Ctr, Cleveland, OH 44106 USA. [Haemaelaeinen, M. S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 266 EP 266 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472001143 ER PT J AU San-Juan, D Maldonado, LB Garduno, AJO Gonzalez-Aragon, MF Pathmanathan, JS Trenado, C Fregni, F AF San-Juan, D. Maldonado, L. B. Garduno, A. J. O. Gonzalez-Aragon, M. F. Pathmanathan, J. S. Trenado, C. Fregni, F. TI A RANDOMIZED CONTROLLED TRIAL OF CATHODAL TRANSCRANIAL DIRECT CURRENT STIMULATION IN PATIENTS WITH MULTIFOCAL EPILEPSY REFRACTORY TO PHARMACOLOGICAL TREATMENT SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [San-Juan, D.; Maldonado, L. B.; Garduno, A. J. O.; Gonzalez-Aragon, M. F.] Inst Nacl Neurol & Neurocirug, Mexico City, DF, Mexico. [Pathmanathan, J. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA USA. [Trenado, C.] Freiburg Univ Hosp, Freiburg, Germany. [Fregni, F.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Fregni, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 289 EP 290 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472001219 ER PT J AU Bartnikas, TB Steinbicker, AU Campagna, DR Blevins, S Woodward, LS Herrera, C Bloch, KD Justice, MJ Fleming, MD AF Bartnikas, Thomas B. Steinbicker, Andrea U. Campagna, Dean R. Blevins, Sherika Woodward, Lanette S. Herrera, Carolina Bloch, Kenneth D. Justice, Monica J. Fleming, Mark D. TI Identification and characterization of a novel murine allele of Tmprss6 SO HAEMATOLOGICA LA English DT Article ID IRON-DEFICIENCY ANEMIA; TRANSMEMBRANE SERINE-PROTEASE; GENOME-WIDE ASSOCIATION; MATRIPTASE-2 TMPRSS6; HEPCIDIN EXPRESSION; MICROCYTIC ANEMIA; COMMON VARIANTS; MUTATIONS; GENE; MICE AB Mutagenesis screens can establish mouse models of utility for the study of critical biological processes such as iron metabolism. Such screens can produce mutations in novel genes or establish novel alleles of known genes, both of which can be useful tools for study. In order to identify genes of relevance to hematologic as well as other phenotypes, we performed N-ethyl-N-nitrosourea mutagenesis in C57BL/6J mice. An anemic mouse was identified and a putative mutation was characterized by mapping, sequencing and in vitro activity analysis. The mouse strain was backcrossed for ten generations then phenotypically characterized with respect to a previously established null mouse strain. Potential modifying loci were identified by quantitative trait locus analysis. Mapping and sequencing in an anemic mouse termed hem8 identified an I286F substitution in Tmprss6, a serine protease essential for iron metabolism; this substitution impaired in vitro protease activity. After backcrossing to C57BL6/J for ten generations, the hem8(-/-) strain exhibited a phenotype similar in some but not all aspects to that of Tmprss6(-/-) mice. The hem8 and Tmprss6-null mutations were allelic. Both hem8(-/-) and Tmprss6(-/-) mice responded similarly to pharmacological modulators of bone morphogenetic protein signaling, a key regulator of iron metabolism. Quantitative trait locus analysis in the hem8 strain identified potential modifying loci on chromosomes 2, 4, 7 and 10. In conclusion, the hem8 mouse model carries a novel allele of Tmprss6. Potential uses for this strain in the study of iron metabolism are discussed. C1 [Bartnikas, Thomas B.; Herrera, Carolina] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Steinbicker, Andrea U.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Steinbicker, Andrea U.] Univ Munster, Dept Anesthesiol Intens Care & Pain Med, D-48149 Munster, Germany. [Campagna, Dean R.; Blevins, Sherika; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Woodward, Lanette S.; Justice, Monica J.] Baylor Coll Med, Dept Genet, Houston, TX 77030 USA. RP Bartnikas, TB (reprint author), Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. EM Thomas_Bartnikas@brown.edu FU National Institutes of Health [K99DK084122, R01DK082971, U01HD039372, R01CA115503, R01DK080011]; Deutsche Forschungsgemeinschaft [DFG SW 119/3-1]; Fondation Leducq FX This work was supported by National Institutes of Health grants K99DK084122 (to TBB), R01DK082971 (to KDB), U01HD039372 and R01CA115503 (to MJJ) and R01DK080011 (to MDF), Deutsche Forschungsgemeinschaft DFG SW 119/3-1 (to AUS) and a grant from the Fondation Leducq (to KDB). NR 48 TC 2 Z9 2 U1 0 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2013 VL 98 IS 6 BP 854 EP 861 DI 10.3324/haematol.2012.074617 PG 8 WC Hematology SC Hematology GA 157MH UT WOS:000319899800010 PM 23300183 ER PT J AU Brown, JR Messmer, B Werner, L Davids, MS Mikler, E Supko, JG Fisher, DC LaCasce, AS Armand, P Jacobsen, E Dalton, V Tesar, B Fernandes, SM McDonough, S Ritz, J Rassenti, L Kipps, TJ Neuberg, D Freedman, AS AF Brown, Jennifer R. Messmer, Bradley Werner, Lillian Davids, Matthew S. Mikler, Evgeny Supko, Jeffrey G. Fisher, David C. LaCasce, Ann S. Armand, Philippe Jacobsen, Eric Dalton, Virginia Tesar, Bethany Fernandes, Stacey M. McDonough, Sean Ritz, Jerome Rassenti, Laura Kipps, Thomas J. Neuberg, Donna Freedman, Arnold S. TI A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma SO HAEMATOLOGICA LA English DT Article ID SALVAGE THERAPY; FLUDARABINE; METHYLPREDNISOLONE; CYCLOPHOSPHAMIDE; COMBINATION; TRIAL; GUIDELINES; CAMPATH-1H; DIAGNOSIS AB This study assessed the safety and preliminary efficacy of escalated dose subcutaneous alemtuzumab in combination with rituximab in chronic lymphocytic leukemia. Twenty-eight patients with relapsed refractory chronic lymphocytic leukemia were treated on four dosing cohorts of weekly rituximab at 375 mg/m(2) and alemtuzumab doses that started at 30 mg three times per week and escalated to weekly dosing over four weeks, culminating with 90 mg weekly. One dose limiting toxicity of a rituximab infusion reaction was seen in cohort 2, but the regimen was otherwise well tolerated without evidence of differential toxicity by cohort. The overall response rate by National Cancer Institute-Working Group criteria was 61%, and the rate of complete bone marrow response was 43%, most of whom were negative for minimal residual disease. The addition of CT scan evaluation per International Workshop on Chronic Lymphocytic Leukemia 2008 criteria reduced the overall response rate to 14%. Median overall survival was 35 months, with 12 patients able to proceed to stem cell transplantation. Pharmacokinetic studies showed that chronic lymphocytic leukemia involving more than 80% of the bone marrow at study start was associated with lower trough concentrations of alemtuzumab and rituximab, and that higher trough serum concentrations of alemtuzumab were associated with complete bone marrow clearance. We conclude that escalated subcutaneous doses of alemtuzumab given weekly are well tolerated and result in excellent bone marrow clearance of chronic lymphocytic leukemia, helping patients to proceed to stem cell transplantation. This study is registered at ClinicalTrials.gov (Identifier:00330252). C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Dept Med Oncol, Boston, MA 02115 USA. EM jbrown2@partners.org FU NIH [K23 CA115682-01] FX JRB was supported by NIH grant K23 CA115682-01 and is a Scholar of the American Society of Hematology as well as a Scholar in Clinical Research of the Leukemia and Lymphoma Society. NR 28 TC 7 Z9 7 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2013 VL 98 IS 6 BP 964 EP 970 DI 10.3324/haematol.2013.086207 PG 7 WC Hematology SC Hematology GA 157MH UT WOS:000319899800025 PM 23645694 ER PT J AU Ioannou, GN Bryson, CL Weiss, NS Scott, JD Boyko, EJ AF Ioannou, George N. Bryson, Christopher L. Weiss, Noel S. Scott, John D. Boyko, Edward J. TI The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection: Are the data found in this sample applicable to other settings? Reply SO HEPATOLOGY LA English DT Letter C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. [Bryson, Christopher L.; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. [Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Scott, John D.] Univ Washington, Div Infect Dis, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2013 VL 57 IS 6 BP 2545 EP 2545 DI 10.1002/hep.26171 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 162PC UT WOS:000320276400053 PM 23197437 ER PT J AU Bleier, BS Nocera, AL Iqbal, H Hoang, JD Feldman, RE Han, X AF Bleier, Benjamin S. Nocera, Angela L. Iqbal, Hufsa Hoang, John D. Feldman, Rachel E. Han, Xue TI P-glycoprotein functions as an immunomodulator in healthy human primary nasal epithelial cells SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE P-glycoprotein; multidrug resistance; nasal epithelium; cell culture; cytokine secretion; immunomodulator; PSC 833; verapamil; rhodamine 123; sinusitis ID CHRONIC RHINOSINUSITIS; EXPRESSION; TRANSPORT; POLYPS; MRP1 AB Background P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent efflux pump that confers chemotherapeutic resistance in cancer cells. Recent studies suggest that P-gp may also function as an immunomodulator through regulation of cytokine transport. Sinonasal epithelial cells have been recognized as drivers of local innate and adaptive immunity and are known to overexpress P-gp in the setting of inflammation. The objective of this study is to therefore determine whether P-gp participates in the regulation of cytokine secretion in sinonasal epithelial cells. Methods Primary nasal epithelial cell cultures (PNECCs) were cultivated from 5 healthy patients. Membranous P-gp was quantified through quantitative fluorescent immunohistochemistry (Q-FIHC) and confirmed by enzyme-linked immunosorbent assay (ELISA). Sensitivity to inhibition was determined using a rhodamine 123 accumulation assay. Baseline and lipopolysaccharide (LPS)-stimulated cytokine secretion of interleukin 6 (IL-6), IL-8, granulocyte macrophage colony stimulating factor (GM-CSF), and thymic stromal lymphopoietin (TSLP) were quantified by ELISA and compared to LPS stimulated secretion in the setting of P-gp-specific inhibition. Differences in P-gp expression and cytokine secretion were compared using 2-tailed Student t tests with post hoc testing using the Bonferroni procedure. Results Membranous P-gp is detectable in PNECCs and upregulated following LPS exposure. P-gp is sensitive to inhibition by both PSC 833 and verapamil in a dose-dependent fashion. LPS stimulated secretion of normalized IL-6 (mean, 95% confidence interval [CI]) (79.67, 42.26-117.07), GM-CSF (39.92, 7.90-71.94), and TSLP (6.65, 5.35-7.96) was significantly reduced following P-gp inhibition (37.60, 11.54-63.65, p = 0.023; 7.64, 2.25-13.03, p = 0.044; and 5.13, 4.44-5.82, p = 0.038; respectively). Conclusion P-gp is functionally active in PNECCs. P-gp participates in modulation of epithelial secretion of LPS stimulated IL-6, GM-CSF, and TSLP. C1 [Bleier, Benjamin S.; Feldman, Rachel E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Nocera, Angela L.; Iqbal, Hufsa; Hoang, John D.; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Bleier, BS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02115 USA. EM benjamin_bleier@meei.harvard.edu FU American Rhinologic Society FX Funding sources for the study: Funded in part by a American Rhinologic Society New Investigator Grant. NR 16 TC 13 Z9 13 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JUN PY 2013 VL 3 IS 6 BP 433 EP 438 DI 10.1002/alr.21166 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 171LG UT WOS:000320929300002 PM 23520057 ER PT J AU Klein, C Krainc, D AF Klein, Christine Krainc, Dimitri TI Glucocerebrosidase Mutations Tipping Point Toward Parkinson Disease and Dementia? SO JAMA NEUROLOGY LA English DT Editorial Material ID LEWY BODY DISEASE; SYNUCLEIN; ALPHA; EXPRESSION; PATHOLOGY C1 [Klein, Christine] Univ Lubeck, Inst Neurogenet, D-23562 Lubeck, Germany. [Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Neurodegenerat Dis,Dept Neurol, Boston, MA USA. RP Klein, C (reprint author), Univ Lubeck, Inst Neurogenet, Maria Goeppert Str 1, D-23562 Lubeck, Germany. EM christine.klein@neuro.uni-luebeck.de NR 11 TC 0 Z9 0 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2013 VL 70 IS 6 BP 686 EP 688 DI 10.1001/jamaneurol.2013.87 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 160PV UT WOS:000320132600002 PM 23588619 ER PT J AU Dombroski, BA Galasko, DR Mata, IF Zabetian, CP Craig, UK Garruto, RM Oyanagi, K Schellenberg, GD AF Dombroski, Beth A. Galasko, Douglas R. Mata, Ignacio F. Zabetian, Cyrus P. Craig, Ulla-Katrina Garruto, Ralph M. Oyanagi, Kiyomitsu Schellenberg, Gerard D. TI C9orf72 Hexanucleotide Repeat Expansion and Guam Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex SO JAMA NEUROLOGY LA English DT Article ID KII PENINSULA; JAPAN; DISEASE; RISK; TAU; MUTATIONS; REGION; GENE; FTD; ALS AB Importance: High-prevalence foci of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) exist in Japanese on the Kii Peninsula of Japan and in the Chamorros of Guam. Clinical and neuropathologic similarities suggest that the disease in these 2 populations may be related. Recent findings showed that some of the Kii Peninsula ALS cases had pathogenic C9orf72 repeat expansions, a genotype that causes ALS in Western populations. Objectives: To perform genotyping among Guam residents to determine if the C9orf72 expanded repeat allele contributes to ALS-PDC in this population and to evaluate LRRK2 for mutations in the same population. Design and Setting: Case-control series from neurodegenerative disease research programs on Guam that screened residents for ALS, PDC, and dementia. Participants: Study participants included 24 with ALS and 22 with PDC and 43 older control subjects with normal cognition ascertained between 1956 and 2006. All but one participant were Chamorro, the indigenous people of Guam. A single individual of white race/ethnicity with ALS was ascertained on Guam during the study. Main Outcomes and Measures: Participants were screened for C9orf72 hexanucleotide repeat length. Participants with repeat numbers in great excess of 30 were considered to have pathogenic repeat expansions. LRRK2 was screened for point mutations by DNA sequencing. Results: We found a single individual with an expanded pathogenic hexanucleotide repeat. This individual of white race/ethnicity with ALS was living on Guam at the time of ascertainment but had been born in the United States. All Chamorro participants with ALS and PDC and control subjects had normal repeats, ranging from 2 to 17 copies. No pathogenic LRRK2 mutations were found. Conclusions and Relevance: Unlike participants with ALS from the Kii Peninsula, C9orf72 expansions do not cause ALS-PDC in Chamorros. Likewise, LRRK2 mutations do not cause Guam ALS-PDC. C1 [Dombroski, Beth A.; Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Garruto, Ralph M.] SUNY Binghamton, Lab Biomed Anthropol & Neurosci, Grad Program Biomed Anthropol, Binghamton, NY USA. [Oyanagi, Kiyomitsu] Tokyo Metropolitan Inst Neurosci, Dept Neuropathol, Tokyo, Japan. RP Schellenberg, GD (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Stellar Chance Labs, Room 609B,422 Curie Blvd, Philadelphia, PA 19104 USA. EM gerardsc@mail.med.upenn.edu OI Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306 FU National Institute on Aging [AG14382, P01-AG-017586, R37 AG11762]; National Institute of Neurological Disorders and Stroke [R01 NS065070] FX This work was supported by grants AG14382, P01-AG-017586, and R37 AG11762 from the National Institute on Aging and by grant R01 NS065070 from the National Institute of Neurological Disorders and Stroke. NR 20 TC 10 Z9 11 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2013 VL 70 IS 6 BP 742 EP 745 DI 10.1001/jamaneurol.2013.1817 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 160PV UT WOS:000320132600010 PM 23588498 ER PT J AU Jadhav, AP Zenonos, G Pless, M Jovin, TG Wechsler, L AF Jadhav, Ashutosh P. Zenonos, Georgios Pless, Misha Jovin, Tudor G. Wechsler, Lawrence TI A Variant of the Anterior Opercular Syndrome With Supranuclear Gaze Palsy SO JAMA NEUROLOGY LA English DT Editorial Material C1 [Jadhav, Ashutosh P.; Jovin, Tudor G.; Wechsler, Lawrence] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. [Zenonos, Georgios] Univ Pittsburgh, Med Ctr, Dept Neurosurg, Pittsburgh, PA 15213 USA. [Pless, Misha] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Jadhav, AP (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, Kaufmann Med Bldg,Ste 811,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jadhavap@upmc.edu NR 3 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 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2013 VL 70 IS 6 BP 800 EP 801 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 160PV UT WOS:000320132600023 PM 23753964 ER PT J AU Amparo, F Dastjerdi, MH Okanobo, A Ferrari, G Smaga, L Hamrah, P Jurkunas, U Schaumberg, DA Dana, R AF Amparo, Francisco Dastjerdi, Mohammad H. Okanobo, Andre Ferrari, Giulio Smaga, Leila Hamrah, Pedram Jurkunas, Ula Schaumberg, Debra A. Dana, Reza TI Topical Interleukin 1 Receptor Antagonist for Treatment of Dry Eye Disease SO JAMA OPHTHALMOLOGY LA English DT Article ID KERATOCONJUNCTIVITIS SICCA; OPHTHALMIC EMULSION; CORNEAL EPITHELIUM; DESICCATING STRESS; TEAR FLUID; CYCLOSPORINE; PREVALENCE; CELLS; CONJUNCTIVA; EXPRESSION AB Importance: The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. Objective: To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. Design and Setting: Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. Participants: Seventy-five patients with refractory DED. Interventions: Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. Main Outcomes and Measures: Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. Results: Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms. Conclusions and Relevance: Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. C1 [Amparo, Francisco; Dastjerdi, Mohammad H.; Okanobo, Andre; Ferrari, Giulio; Smaga, Leila; Hamrah, Pedram; Jurkunas, Ula; Dana, Reza] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Schaumberg, Debra A.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu RI ferrari, giulio/J-9260-2016 OI ferrari, giulio/0000-0001-6474-9908 FU Pfizer Inc; National Institutes of Health [K24 EY019098] FX Drs Dastjerdi and Dana report being listed as coinventors in a patent application pertaining to use of IL-1 blockers for ophthalmic use, licensed by Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary to Eleven Biotherapeutics Inc. Dr Schaumberg reports receiving support from Pfizer Inc; holding investments in Mimetogen and TearLab; being a consultant to Alcon, Allergan, Celtic, Eleven Biotherapeutics Inc, Inspire, Mimetogen, Pfizer Inc, and SARcode Bioscience; holding a proprietary interest in patent 11873478 covering compositions and methods for treating eye disorders and conditions; and receiving honoraria from Allergan and Pfizer Inc. Dr Dana reports holding equity in Eleven Biotherapeutics Inc.; This study was supported in part by grant K24 EY019098 from the National Institutes of Health (Drs Amparo, Dastjerdi, Okanobo, Ferrari, and Dana and Ms Smaga). NR 43 TC 27 Z9 27 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2013 VL 131 IS 6 BP 715 EP 723 DI 10.1001/jamaophthalmol.2013.195 PG 9 WC Ophthalmology SC Ophthalmology GA 170LR UT WOS:000320852700001 PM 23599118 ER PT J AU Schmidt, TA Sullivan, DA Knop, E Richards, SM Knop, N Liu, SH Sahin, A Darabad, RR Morrison, S Kam, WR Sullivan, BD AF Schmidt, Tannin A. Sullivan, David A. Knop, Erich Richards, Stephen M. Knop, Nadja Liu, Shaohui Sahin, Afsun Darabad, Raheleh Rahimi Morrison, Sheila Kam, Wendy R. Sullivan, Benjamin D. TI Transcription, Translation, and Function of Lubricin, a Boundary Lubricant, at the Ocular Surface SO JAMA OPHTHALMOLOGY LA English DT Article ID DRY EYE DISEASE; ARTICULAR-CARTILAGE; SYNOVIAL-FLUID; HYALURONIC-ACID; PROTEOGLYCAN 4; WORKSHOP 2007; ZONE PROTEIN; RECOMBINANT LUBRICIN; ARTIFICIAL MOUTH; LID WIPER AB Importance: Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear. Objective: To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage. Design, Setting, and Participants: Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage. Results: Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions. Conclusions and Relevance: Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage. C1 [Schmidt, Tannin A.; Morrison, Sheila] Univ Calgary, Fac Kinesiol, Human Performance Lab, Calgary, AB, Canada. [Schmidt, Tannin A.] Univ Calgary, Schulich Sch Engn, Ctr Bioengn Res & Educ, Calgary, AB, Canada. [Sullivan, David A.; Richards, Stephen M.; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Kam, Wendy R.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Sullivan, David A.; Richards, Stephen M.; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Kam, Wendy R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Knop, Erich; Knop, Nadja] Charite, Dept Anat, OSCB, D-13353 Berlin, Germany. [Sullivan, Benjamin D.] TearLab Corp, San Diego, CA USA. RP Sullivan, DA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM david.sullivan@schepens.harvard.edu FU National Institutes of Health [R01EY05612, 5 U42 RR006042]; Margaret S. Sinon Scholar in Ocular Surface Research fund; Natural Sciences and Engineering Research Council of Canada; Canadian Arthritis Network; Faculty of Kinesiology at the University of Calgary; Schulich School of Engineering Centre for Bioengineering Research and Education at the University of Calgary FX This research was supported by National Institutes of Health grant R01EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research fund, and funding from the Natural Sciences and Engineering Research Council of Canada, the Canadian Arthritis Network, and the Faculty of Kinesiology and the Schulich School of Engineering Centre for Bioengineering Research and Education at the University of Calgary. We acknowledge use of tissues procured by the National Disease Research Interchange with support from National Institutes of Health grant 5 U42 RR006042. NR 63 TC 19 Z9 20 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2013 VL 131 IS 6 BP 766 EP 776 DI 10.1001/jamaophthalmol.2013.2385 PG 11 WC Ophthalmology SC Ophthalmology GA 170LR UT WOS:000320852700008 PM 23599181 ER PT J AU Palioura, S Piris, A Chodosh, J AF Palioura, Sotiria Piris, Adriano Chodosh, James TI Conjunctivitis, Fever, and Tender Skin Nodules SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID FEBRILE NEUTROPHILIC DERMATOSIS; SWEETS-SYNDROME; INVOLVEMENT C1 [Palioura, Sotiria; Chodosh, James] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Piris, Adriano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2013 VL 131 IS 6 BP 791 EP 793 PG 3 WC Ophthalmology SC Ophthalmology GA 170LR UT WOS:000320852700015 PM 23764707 ER PT J AU Afshar, R Strassner, JP Seung, E Causton, B Cho, JL Harris, RS Hamilos, DL Medoff, BD Luster, AD AF Afshar, Roshi Strassner, James P. Seung, Edward Causton, Benjamin Cho, Josalyn L. Harris, R. Scott Hamilos, Daniel L. Medoff, Benjamin D. Luster, Andrew D. TI Compartmentalized chemokine-dependent regulatory T-cell inhibition of allergic pulmonary inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; regulatory T cells; chemokines; CCR4; CCR7; segmental allergen challenge ID RECEPTOR EXPRESSION; AIRWAY INFLAMMATION; ASTHMA; CCR7; DISEASE; HYPERRESPONSIVENESS; INDUCTION; TOLERANCE; MIGRATION; SUBSETS AB Background: Induction of endogenous regulatory T (Treg) cells represents an exciting new potential modality for treating allergic diseases, such as asthma. Treg cells have been implicated in the regulation of asthma, but the anatomic location in which they exert their regulatory function and the mechanisms controlling the migration necessary for their suppressive function in asthma are not known. Understanding these aspects of Treg cell biology will be important for harnessing their power in the clinic. Objective: We sought to determine the anatomic location at which Treg cells exert their regulatory function in the sensitization and effector phases of allergic asthma and to determine the chemokine receptors that control the migration of Treg cells to these sites in vivo in both mice and human subjects. Methods: The clinical efficacy and anatomic location of adoptively transferred chemokine receptor-deficient CD4(+)CD25(+) forkhead box protein 3-positive Treg cells was determined in the sensitization and effector phases of allergic airway inflammation in mice. The chemokine receptor expression profile was determined on Treg cells recruited into the human airway after bronchoscopic segmental allergen challenge of asthmatic patients. Results: We show that CCR7, but not CCR4, is required on Treg cells to suppress allergic airway inflammation during the sensitization phase. In contrast, CCR4, but not CCR7, is required on Treg cells to suppress allergic airway inflammation during the effector phase. Consistent with our murine studies, human subjects with allergic asthma had an increase in CCR4-expressing functional Treg cells in the lungs after segmental allergen challenge. Conclusion: The location of Treg cell function differs during allergic sensitization and allergen-induced recall responses in the lung, and this differential localization is critically dependent on differential chemokine function. C1 [Afshar, Roshi; Strassner, James P.; Seung, Edward; Causton, Benjamin; Cho, Josalyn L.; Hamilos, Daniel L.; Medoff, Benjamin D.; Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Cambridge, MA 02138 USA. [Causton, Benjamin; Cho, Josalyn L.; Harris, R. Scott; Medoff, Benjamin D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Cambridge, MA 02138 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, 149,13th St, Charlestown, MA 02129 USA. EM aluster@mgh.harvard.edu FU National Institutes of Health [R37AI0406, U19AI095261, T32 AI060548]; Merck; United Therapeutics FX Supported by grants from the National Institutes of Health (R37AI0406, U19AI095261, and T32 AI060548 to A.D.L.).; Disclosure of potential conflict of interest: D. L. Hamilos has consultant arrangements with and has received grants from Merck. R. S. Harris has consultant arrangements with Merck and has received grants from United Therapeutics. A. D. Luster has consultant arrangements with Amgen, Idera, Lilly, and Merck. The rest of the authors declare that they have no relevant conflicts of interest. NR 32 TC 12 Z9 13 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2013 VL 131 IS 6 BP 1644 EP + DI 10.1016/j.jaci.2013.03.002 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 166CT UT WOS:000320532800025 PM 23632297 ER PT J AU Hernandez, AF Hammill, BG Kociol, RD Eapen, ZJ Fonarow, GC Klaskala, W Mills, RM Curtis, LH AF Hernandez, Adrian F. Hammill, Bradley G. Kociol, Robb D. Eapen, Zubin J. Fonarow, Gregg C. Klaskala, Winslow Mills, Roger M. Curtis, Lesley H. TI Clinical Effectiveness of Anticoagulation Therapy Among Older Patients With Heart Failure and Without Atrial Fibrillation: Findings From the ADHERE Registry Linked to Medicare Claims SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Atrial fibrillation; anticoagulants; heart failure; outcome assessment (health care) ID LEFT-VENTRICULAR DYSFUNCTION; SYSTOLIC DYSFUNCTION; SINUS RHYTHM; ANTITHROMBOTIC THERAPY; RANDOMIZED-TRIAL; RISK; BENEFICIARIES; WARFARIN; OUTCOMES; STROKE AB Background: Patients with heart failure are at higher risk for thromboembolic events, even in the absence of atrial fibrillation, but the effect of anticoagulation therapy on outcomes is uncertain. Methods and Results: With data from a clinical registry linked to Medicare claims, we estimated the adjusted associations between anticoagulation and 1-year outcomes with the use of inverse probability of treatment weighting. Eligible patients had an ejection fraction <= 35%, had no concurrent atrial fibrillation, were alive at discharge, and had not received anticoagulation therapy before admission. Of 13,217 patients in 276 hospitals, 1,140 (8.6%) received anticoagulation therapy at discharge. Unadjusted rates of thromboembolic events and major adverse cardiovascular events did not differ by receipt of anticoagulation therapy. Patients discharged on anticoagulation therapy had lower unadjusted rates of all-cause mortality (27.2% vs 32.3%; P < .001) and readmission for heart failure (29.4% vs 35.4%; P < .001) and higher rates of bleeding events (5.2% vs 2.8%; P < .001). After adjustment for probability of treatment and discharge medications, there were no differences in all-cause mortality (hazard ratio 0.92; 95% confidence interval 0.80-1.06) or readmission for heart failure (0.91, 0.81-1.02), but patients receiving anticoagulation therapy were at higher risk for bleeding events (2.09, 1.47-2.97). Conclusions: Anticoagulation therapy at discharge is infrequent among older patients with heart failure and without atrial fibrillation. There were no statistically significant propensity-weighted associations between anticoagulation therapy and 1-year outcomes, except for a higher risk of bleeding. C1 [Hernandez, Adrian F.; Hammill, Bradley G.; Eapen, Zubin J.; Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Hernandez, Adrian F.; Eapen, Zubin J.; Curtis, Lesley H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Kociol, Robb D.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. [Kociol, Robb D.] Beth Israel Deaconess Med Ctr, CardioVasc Inst, Boston, MA 02215 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Klaskala, Winslow; Mills, Roger M.] Janssen Res & Dev LLC, Raritan, NJ USA. RP Hernandez, AF (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM adrian.hernandez@duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Duke University; Johnson Johnson; Amylin; American Heart Association Pharmaceutical Roundtable FX Funding: Research agreement between Duke University and Johnson & Johnson.; Dr Hernandez has received research funding (>$10,000) from Amylin and Johnson & Johnson and honoraria (<$10,000) from Corthera. Dr Eapen has received research fellowship funding (>$10,000) from the American Heart Association Pharmaceutical Roundtable. Dr Fonarow is a consultant or advisory board member with Novartis (>$10,000), Medtronic (<$10,000), and Gambro (<$10,000). Dr Mills is a full-time employee of Janssen Research and Development, a subsidiary of Johnson & Johnson. Dr Curtis has received research funding (>$10,000) from Johnson & Johnson. Drs Hernandez and Curtis have made available online detailed listings of financial disclosures (http://www.dcri.duke.edu/about-us/conflict-of-interest/). NR 26 TC 1 Z9 1 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2013 VL 19 IS 6 BP 401 EP 407 DI 10.1016/j.cardfail.2013.04.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167NX UT WOS:000320639800004 PM 23743489 ER PT J AU Jaussaud, N Chitsaz, S Meadows, A Wintermark, M Cambronero, N Azadani, AN Saloner, DA Chuter, TA Tseng, EE AF Jaussaud, N. Chitsaz, S. Meadows, A. Wintermark, M. Cambronero, N. Azadani, A. N. Saloner, D. A. Chuter, T. A. Tseng, E. E. TI Acute type A aortic dissection intimal tears by 64-slice computed tomography: a role for endovascular stent-grafting? SO JOURNAL OF CARDIOVASCULAR SURGERY LA English DT Article DE Aorta; Tomography, spiral computed; Lacerations ID INTERNATIONAL REGISTRY; SURGICAL-TREATMENT; THORACIC AORTA; MANAGEMENT; REPAIR; ANEURYSM; OUTCOMES; DISEASE; CT; PLACEMENT AB Aim. The goal of this study was to identify physical characteristics of primary intimal tears in patients arriving to the hospital alive with acute type A aortic dissection using 64-multislice computerized tomography (MSCT) in order to determine anatomic feasibility of endovascular stent-grafting (ESG) for future treatment. Methods. Radiology database was screened for acute type A aortic dissection since the time of acquisition of the 64-slice CT scanner and cross-referenced with surgical database. Seventeen patients met inclusion criteria. Images were reviewed for number, location, and size of intimal tears and aortic dimensions. Potential obstacles for ESG were determined. Results. Ascending aorta (29%) and sinotubular junction (29%) were the most frequent regions where intimal tears originated. Location of intimal tears in nearly 75% of patients was inappropriate for ESG, and 94% of patients did not have sufficient proximal or distal landing zone required for secure fixation. Only 71% of patients underwent surgical aortic dissection repair after imaging and 86% of entry tears detected on MSCT were confirmed on intraoperative documentation. Only one patient would have met all technical criteria for ESG using currently available devices. Conclusion. Location of intimal tear, aortic valve insufficiency, aortic diameter>38mm are major factors limiting use of ESG for acute type A dissection. Available stents used to treat type B aortic dissection do not address anatomic constraints present in type A aortic dissection in the majority of cases, such that development of new devices would be required. C1 [Jaussaud, N.; Chitsaz, S.; Cambronero, N.; Azadani, A. N.; Chuter, T. A.; Tseng, E. E.] Univ Calif San Francisco, Dept Surg, Med Ctr, Div Cardiothorac Surg, San Francisco, CA USA. [Jaussaud, N.; Chitsaz, S.; Meadows, A.; Wintermark, M.; Cambronero, N.; Azadani, A. N.; Saloner, D. A.; Chuter, T. A.; Tseng, E. E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Meadows, A.; Wintermark, M.; Saloner, D. A.] Univ Calif San Francisco, Med Ctr, Dept Radiol, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF Med Ctr, 500 Parnassus Ave Suite 405W Box 0118, San Francisco, CA 94143 USA. EM Elaine.Tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008; OI Wintermark, Max/0000-0002-6726-3951 FU American Heart Association; Northern California Institute for Research and Education; Federation Francaise de Cardiologie/Societe Frangaise de Cardiologie, Societe Francaise de Chirurugie Thoracique et Cardio-Vasculaire FX This work was supported by American Heart Association, Northern California Institute for Research and Education, and Federation Francaise de Cardiologie/Societe Francaise de Cardiologie, Societe Francaise de Chirurugie Thoracique et Cardio-Vasculaire. NR 36 TC 5 Z9 5 U1 0 U2 0 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 JUN PY 2013 VL 54 IS 3 BP 373 EP 381 PG 9 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA 168YF UT WOS:000320743200008 PM 22820738 ER PT J AU Guddati, AK Shaheen, S AF Guddati, Achuta K. Shaheen, Shagufta TI Characterization of disease progression in ovarian cancer by utilizing 'chemograms' of ovarian cancer stem cells SO JOURNAL OF CHEMOTHERAPY LA English DT Article DE Chemogram; Ovarian cancer; Cancer stem cells; Chemotherapy ID GENE-EXPRESSION PROFILE; MULLERIAN-INHIBITING SUBSTANCE; ACUTE MYELOID-LEUKEMIA; LABEL-RETAINING CELLS; SIDE-POPULATION CELLS; CISPLATIN RESISTANCE; INITIATING CELLS; PROGNOSTIC VALUE; LOW-GRADE; STEM/PROGENITOR CELLS AB Introduction: Ovarian cancer is one of the leading causes of death in women with cancer. First-line chemotherapy with platinum compounds and taxane compounds has been effective, but most patients develop a relapse of the disease due to drug resistance. There is growing evidence that this resistance may be due to the presence of ovarian cancer stem cells. Discussion: Cells with properties of cancer stem cells have been isolated from the ascitic fluid of ovarian cancer patients. This subset of cells is highly tumourigenic compared to the rest of the cells in the ascitic fluid. They are known to exude harmful chemicals from their cytoplasm and have been found to be resistant to chemotherapeutic agents. This property has been utilized to purify them by fluorescence assisted cytometry to yield a subset of cells which are called 'side population'. These cells exhibit the properties of cancer stem cells and their role in disease progression is being currently investigated. The course of the disease can be potentially characterized at the cellular level by closely studying this cell population. They can also be cultured in different combinations of chemotherapeutic agents at varying concentrations to obtain 'chemograms' which are sensitivity charts. Chemotherapeutic agents which produce the most effective kill curves can then be rationally used as a second-line chemotherapy if the disease relapses. These sensitivity charts can provide insight into emerging patterns of chemoresistance and also help discover surface markers that accurately identify ovarian cancer stem cells. Conclusion: The high rate of disease relapse in patients with ovarian cancer requires a new and different approach utilizing the sensitivity of cancer stem cells. Isolating and characterizing the resistance patterns of ovarian cancer stem cells may provide a rational approach towards an effective and individualized chemotherapeutic regimen. C1 [Guddati, Achuta K.; Shaheen, Shagufta] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. RP Guddati, AK (reprint author), Massachusetts Gen Hosp, 50 Fruit St, Boston, MA 02114 USA. EM aguddati@partners.org NR 90 TC 0 Z9 0 U1 0 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD JUN PY 2013 VL 25 IS 3 BP 184 EP 191 DI 10.1179/1973947812Y.0000000058 PG 8 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 152AB UT WOS:000319500400009 PM 23783145 ER PT J AU McCarthy, A Farrell, M Hedley-Whyte, T McGuone, D Kavanagh, E McNally, S Keogan, M Horgan, N Lynch, T O'Rourke, K AF McCarthy, A. Farrell, M. Hedley-Whyte, T. McGuone, D. Kavanagh, E. McNally, S. Keogan, M. Horgan, N. Lynch, T. O'Rourke, K. TI Granulomatosis with polyangiitis masquerading as giant cell arteritis SO JOURNAL OF NEUROLOGY LA English DT Letter ID WEGENERS-GRANULOMATOSIS C1 [McCarthy, A.; Lynch, T.; O'Rourke, K.] Mater Misericordiae Univ Hosp, Dublin Neurol Inst, Dublin 7, Ireland. [Farrell, M.] Beaumont Hosp, Dept Neuropathol, Dublin 9, Ireland. [Hedley-Whyte, T.; McGuone, D.] Massachusetts Gen Hosp, Dept Pathol, Charles S Kubik Lab Neuropathol, Boston, MA 02114 USA. [Hedley-Whyte, T.; McGuone, D.] Harvard Univ, Sch Med, Boston, MA USA. [Kavanagh, E.] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin 7, Ireland. [McNally, S.] Beaumont Hosp, Dept Neurosurg, Dublin 9, Ireland. [Keogan, M.] Beaumont Hosp, Dept Immunol, Dublin 9, Ireland. [Horgan, N.] Royal Victoria Eye & Ear Hosp, Dublin, Ireland. RP O'Rourke, K (reprint author), Mater Misericordiae Univ Hosp, Dublin Neurol Inst, 57 Eccles St, Dublin 7, Ireland. EM killian.orourke@gmail.com NR 7 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2013 VL 260 IS 6 BP 1661 EP 1663 DI 10.1007/s00415-013-6913-3 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 159LJ UT WOS:000320046600028 PM 23579235 ER PT J AU Serrano-Pozo, A Muzikansky, A Gomez-Isla, T Growdon, JH Betensky, RA Frosch, MP Hyman, BT AF Serrano-Pozo, Alberto Muzikansky, Alona Gomez-Isla, Teresa Growdon, John H. Betensky, Rebecca A. Frosch, Matthew P. Hyman, Bradley T. TI Differential Relationships of Reactive Astrocytes and Microglia to Fibrillar Amyloid Deposits in Alzheimer Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Amyloid plaques; Apolipoprotein E; Astrocytes; Microglia ID APOLIPOPROTEIN-E GENOTYPE; SENILE PLAQUES; A-BETA; CEREBRAL-CORTEX; SIZE DISTRIBUTION; APOE GENOTYPE; PROTEIN; RECEPTOR; BRAIN; ACCUMULATION AB Although it is clear that astrocytes and microglia cluster around dense-core amyloid plaques in Alzheimer disease (AD), whether they are primarily attracted to amyloid deposits or are just reacting to plaque-associated neuritic damage remains elusive. We postulate that astrocytes and microglia may differentially respond to fibrillar amyloid beta. Therefore, we quantified the size distribution of dense-core thioflavin-S (ThioS)-positive plaques in the temporal neocortex of 40 AD patients and the microglial and astrocyte responses in their vicinity (<= 50 mu m) and performed correlations between both measures. As expected, both astrocytes and microglia were clearly spatially associated with ThioS-positive plaques (p = 0.0001, <= 50 mu m vs >= 50 mu m from their edge), but their relationship to ThioS-positive plaque size differed: larger ThioS-positive plaques were associated with more surrounding activated microglia (p = 0.0026), but this effect was not observed with reactive astrocytes. Microglial response to dense-core plaques seems to be proportional to their size, which we postulate reflects a chemotactic effect of amyloid beta. By contrast, plaque-associated astrocytic response does not correlate with plaque size and seems to parallel the behavior of plaque-associated neuritic damage. C1 [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA USA. [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), Bldg 114,16th St 2009, Charlestown, MA 02129 USA. EM bhyman@partners.org OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU National Institutes of Health [P50AG05134, AG08487]; Fundacion Alfonso Martin Escudero (Madrid, Spain) FX This work was funded by the National Institutes of Health (grants P50AG05134 and AG08487). Dr. Alberto Serrano-Pozo was funded by a Research Fellowship from Fundacion Alfonso Martin Escudero (Madrid, Spain). NR 64 TC 31 Z9 31 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 BP 462 EP 471 DI 10.1097/NEN.0b013e3182933788 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400002 PM 23656989 ER PT J AU Rahgozar, K Wright, E Carrithers, LM Carrithers, MD AF Rahgozar, Kusha Wright, Erik Carrithers, Lisette M. Carrithers, Michael D. TI Mediation of Protection and Recovery From Experimental Autoimmune Encephalomyelitis by Macrophages Expressing the Human Voltage-Gated Sodium Channel NaV1.5 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alternative activation; Experimental autoimmune encephalomyelitis; Macrophage; Multiple sclerosis; Sodium channel ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; IMMUNE SURVEILLANCE; ARGINASE-I; INFLAMMATION; ACTIVATION; CELLS; POLARIZATION; REGENERATION; PLASTICITY AB Multiple sclerosis (MS) is the most common nontraumatic cause of neurologic disability in young adults. Despite treatment, progressive tissue injury leads to accumulation of disability in many patients. Here, our goal was to develop an immune-mediated strategy to promote tissue repair and clinical recovery in an MS animal model. We previously demonstrated that a variant of the voltage-gated sodium channel NaV1.5 is expressed intracellularly in human macrophages, and that it regulates cellular signaling. This channel is not expressed in mouse macrophages, which has limited the study of its functions. To overcome this obstacle, we developed a novel transgenic mouse model (C57BL6(c-fms-hSCN5A)), in which the human macrophage NaV1.5 splice variant is expressed in vivo in mouse macrophages. These mice were protected from experimental autoimmune encephalomyelitis, the mouse model of MS. During active inflammatory disease, NaV1.5-positive macrophages were found in spinal cord lesions where they formed phagocytic cell clusters; they expressed markers of alternative activation during recovery. NaV1.5-positive macrophages that were adoptively transferred into wild-type recipients with established experimental autoimmune encephalomyelitis homed to lesions and promoted recovery. These results suggest that NaV1.5-positive macrophages enhance recovery from CNS inflammatory disease and could potentially be developed as a cell-based therapy for the treatment of MS. C1 [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. [Rahgozar, Kusha; Wright, Erik; Carrithers, Lisette M.; Carrithers, Michael D.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Carrithers, Michael D.] Univ Wisconsin, Program Cellular & Mol Pathol, Madison, WI 53706 USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, 1300 Univ Ave,Room 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu FU VA Merit Award from the BLRD service; University of Wisconsin FX This work was supported by a VA Merit Award from the BLR&D service to Michael Carrithers and the University of Wisconsin. NR 42 TC 4 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 BP 489 EP 504 DI 10.1097/NEN.0b013e318293eb08 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400005 PM 23656992 ER PT J AU Edlow, BL Haynes, RL Takahashi, E Klein, JP Cummings, P Benner, T Greer, DM Greenberg, SM Wu, O Kinney, HC Folkerth, RD AF Edlow, Brian L. Haynes, Robin L. Takahashi, Emi Klein, Joshua P. Cummings, Peter Benner, Thomas Greer, David M. Greenberg, Steven M. Wu, Ona Kinney, Hannah C. Folkerth, Rebecca D. TI Disconnection of the Ascending Arousal System in Traumatic Coma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ARAS; Ascending reticular activating system; Coma; Consciousness; HARDI; High angular resolution diffusion imaging; TAI; TBI; Tractography; Traumatic axonal injury; Traumatic brain injury ID DIFFUSE AXONAL INJURY; PERSISTENT VEGETATIVE STATE; AMYLOID PRECURSOR PROTEIN; MINIMALLY CONSCIOUS STATE; CLOSED-HEAD INJURY; BRAIN-INJURY; ALZHEIMERS-DISEASE; NERVOUS-TISSUE; WATER RELAXATION; LATE RECOVERY AB Traumatic coma is associated with disruption of axonal pathways throughout the brain, but the specific pathways involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging to map the connectivity of axonal pathways that mediate the 2 critical components of consciousness-arousal and awareness-in the postmortem brain of a 62-year-old woman with acute traumatic coma and in 2 control brains. High angular resolution diffusion imaging tractography guided tissue sampling in the neuropathologic analysis. High angular resolution diffusion imaging tractography demonstrated complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei. In contrast, hemispheric arousal pathways connecting the thalamus and basal forebrain to the cerebral cortex were only partially disrupted, as were the cortical "awareness pathways." Neuropathologic examination, which used beta-amyloid precursor protein and fractin immunomarkers, revealed axonal injury in the white matter of the brainstem and cerebral hemispheres that corresponded to sites of high angular resolution diffusion imaging tract disruption. Axonal injury was also present within the gray matter of the hypothalamus, thalamus, basal forebrain, and cerebral cortex. We propose that traumatic coma may be a subcortical disconnection syndrome related to the disconnection of specific brainstem arousal nuclei from the thalamus and basal forebrain. C1 [Edlow, Brian L.; Klein, Joshua P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Klein, Joshua P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Folkerth, Rebecca D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Edlow, Brian L.; Takahashi, Emi; Benner, Thomas; Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Edlow, Brian L.; Greer, David M.; Greenberg, Steven M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,J Philip Kistler Stroke Re, Boston, MA 02115 USA. [Takahashi, Emi] Harvard Univ, Sch Med, Div Newborn Med, Boston Childrens Hosp, Boston, MA USA. [Takahashi, Emi] Harvard Univ, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Boston, MA USA. [Cummings, Peter] Off Chief Med Examiner, Boston, MA USA. [Wu, Ona] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, Yale New Haven Hosp, New Haven, CT 06510 USA. [Haynes, Robin L.; Kinney, Hannah C.; Folkerth, Rebecca D.] Harvard Univ, Sch Med, Dept Pathol, Boston Childrens Hosp, Boston, MA 02115 USA. RP Edlow, BL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Lunder 650, Boston, MA 02114 USA. EM bedlow@partners.org RI Haynes, Robin/M-4401-2016 OI Haynes, Robin/0000-0003-4909-9585 FU National Institutes of Health [R25NS065743, R01HD20991, R21HD069001, P41EB015896]; Center for Integration of Medicine & Innovative Technology; Neuropathology Division, Department of Pathology; Department of Neurology, Brigham; Women's Hospital, Boston, Mass; National Center for Research Resources [1S10RR016811-01] FX This work was supported by grants from the National Institutes of Health (R25NS065743 to Brian Edlow, R01HD20991 to Hannah Kinney, R21HD069001 to Emi Takahashi, and P41EB015896 to the Athinoula A. Martinos Center for Biomedical Imaging) and the Center for Integration of Medicine & Innovative Technology (to Brian Edlow). This work was also supported by the Neuropathology Division, Department of Pathology, and the Department of Neurology, Brigham and Women's Hospital, Boston, Mass. This work involved the use of instrumentation supported by the National Center for Research Resources (1S10RR016811-01 to the Athinoula A. Martinos Center for Biomedical Imaging). NR 87 TC 28 Z9 28 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 BP 505 EP 523 DI 10.1097/NEN.0b013e3182945bf6 PG 19 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400006 PM 23656993 ER PT J AU Suva, M Rheinbay, E Louis, D Bernstein, B AF Suva, Mario Rheinbay, Esther Louis, David Bernstein, Bradley TI Epigenetic Determinants of Cellular State in Glioblastoma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 20-23, 2013 CL Charleston, SC SP Amer Assoc Neuropathologists Inc C1 [Suva, Mario; Rheinbay, Esther; Louis, David; Bernstein, Bradley] Massachusetts Gen Hosp, Boston, MA 02114 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 MA 4 BP 541 EP 541 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400012 ER PT J AU Bit-Ivan, E Weintraub, S Hyman, B Arnold, S McCarty-Wood, E Shim, H Suh, E Van Deerlin, V Schneider, J Trojanowski, J Frosch, M Baker, M Rademakers, R Mesulam, MM Bigio, E AF Bit-Ivan, Esther Weintraub, Sandra Hyman, Bradley Arnold, Steven McCarty-Wood, Elisabeth Shim, HyungSub Suh, Eunran Van Deerlin, Vivianna Schneider, Julie Trojanowski, John Frosch, Matthew Baker, Matt Rademakers, Rosa Mesulam, M. Marsel Bigio, Eileen TI A Novel GRN Mutation: Clinicopathologic Report of Four Cases SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 20-23, 2013 CL Charleston, SC SP Amer Assoc Neuropathologists Inc C1 [Bit-Ivan, Esther; Weintraub, Sandra; Shim, HyungSub; Mesulam, M. Marsel; Bigio, Eileen] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Hyman, Bradley; Frosch, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arnold, Steven; McCarty-Wood, Elisabeth; Suh, Eunran; Van Deerlin, Vivianna; Trojanowski, John] Univ Penn, Philadelphia, PA 19104 USA. [Schneider, Julie] Rush Univ, Med Ctr, Chicago, IL USA. [Baker, Matt; Rademakers, Rosa] Mayo Clin Jacksonville, Jacksonville, FL 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 MA 48 BP 552 EP 553 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400056 ER PT J AU Kinney, H Edlow, B Witzel, T Wald, L McNab, J AF Kinney, Hannah Edlow, Brian Witzel, Thomas Wald, Lawrence McNab, Jennifer TI Human Hippocampal-caudal Brainstem Connectivity Determined by the Connectome: Implications for Seizure-Related, Sudden Death SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 20-23, 2013 CL Charleston, SC SP Amer Assoc Neuropathologists Inc C1 [Kinney, Hannah; Edlow, Brian; Witzel, Thomas; Wald, Lawrence; McNab, Jennifer] Harvard Univ, Sch Med, Boston, MA USA. [Edlow, Brian; Witzel, Thomas; Wald, Lawrence; McNab, Jennifer] Mass Gen Hosp, Boston, MA USA. [McNab, Jennifer] Stanford Univ, Stanford, CA 94305 USA. RI Witzel, Thomas/P-1402-2014 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 MA 110 BP 570 EP 570 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400118 ER PT J AU Davidson, C Liu, CH Vitte, J Giovannini, M McClatchey, A AF Davidson, Christian Liu, Ching-Hui Vitte, Jeremie Giovannini, Marco McClatchey, Andrea TI Heterogeneity Dictates Therapeutic Response In Nf2-Mutant Schwann Cells SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 20-23, 2013 CL Charleston, SC SP Amer Assoc Neuropathologists Inc C1 [Davidson, Christian; Liu, Ching-Hui; McClatchey, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vitte, Jeremie; Giovannini, Marco] House Ear Res Inst, Los Angeles, CA USA. RI Vitte, Jeremie/B-9874-2017 OI Vitte, Jeremie/0000-0002-2567-7988 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 MA 129 BP 575 EP 575 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400137 ER PT J AU Santagata, S Eberlin, L Norton, I Ide, J Feldman, D Liu, XH Wiley, J Orringer, D Gill, K Dunn, I Dias-Santagata, D Ligon, K Jolesz, F Golby, A Cooks, R Agar, N AF Santagata, Sandro Eberlin, Livia Norton, Isaiah Ide, Jennifer Feldman, Daniel Liu, Xiaohui Wiley, Joshua Orringer, Daniel Gill, Kristen Dunn, Ian Dias-Santagata, Dora Ligon, Keith Jolesz, Ferencc Golby, Alexandra Cooks, R. Agar, Nathalie TI Metabolite-imaging Mass Spectrometry to Guide Brain Surgery SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 20-23, 2013 CL Charleston, SC SP Amer Assoc Neuropathologists Inc C1 [Santagata, Sandro; Feldman, Daniel; Gill, Kristen; Ligon, Keith] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Norton, Isaiah; Ide, Jennifer; Liu, Xiaohui; Orringer, Daniel; Dunn, Ian; Agar, Nathalie] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Jolesz, Ferencc; Golby, Alexandra] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Eberlin, Livia; Wiley, Joshua; Cooks, R.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Dias-Santagata, Dora] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Cooks, R/G-1051-2015 OI Cooks, R/0000-0002-9581-9603 NR 0 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2013 VL 72 IS 6 MA 131 BP 575 EP 576 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 151IR UT WOS:000319454400139 ER PT J AU Holschneider, DP Guo, YM Wang, Z Roch, M Scremin, OU AF Holschneider, Daniel P. Guo, Yumei Wang, Zhuo Roch, Margareth Scremin, Oscar U. TI Remote Brain Network Changes after Unilateral Cortical Impact Injury and Their Modulation by Acetylcholinesterase Inhibition SO JOURNAL OF NEUROTRAUMA LA English DT Article DE cholinergic; diaschisis; functional brain mapping; functional connectivity; traumatic brain injury ID CEREBRAL BLOOD-FLOW; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; FUNCTIONAL CONNECTIVITY; MOTOR CORTEX; BASAL GANGLIA; RESTING-STATE; RAT-BRAIN; INDICATOR FRACTIONATION; SPATIAL NORMALIZATION AB We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [C-14]-iodoantipyrine. Quantitative autoradiographs were analyzed by statistical parametric mapping and functional connectivity (FC) analysis. CCI resulted in functional deficits in the ipsilesional basal ganglia, with increased activation contralesionally. Recruitment was also observed, especially contralesionally, of the red nucleus, superior colliculus, pedunculopontine tegmental nucleus, thalamus (ventrolateral n., central medial n.), cerebellum, and sensory cortex. FC decreased significantly within ipsi- and contralesional motor circuits and between hemispheres, but increased between midline cerebellum and select regions of the basal ganglia within each hemisphere. Physostigmine significantly increased functional brain activation in the cerebellar thalamocortical pathway (midline cerebellum -> ventrolateral thalamus -> motor cortex), subthalamic nucleus/zona incerta, and red nucleus and bilateral sensory cortex. In conclusion, CCI resulted in increased functional recruitment of contralesional motor cortex and bilateral subcortical motor regions, as well as recruitment of the cerebellar-thalamocortical circuit and contralesional sensory cortex. This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation. C1 [Holschneider, Daniel P.; Guo, Yumei; Wang, Zhuo] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.; Guo, Yumei; Wang, Zhuo] Univ So Calif, Keck Sch Med, Dept Behav Sci, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.; Roch, Margareth; Scremin, Oscar U.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Holschneider, DP (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, 1333 San Pablo St,MCH 51A,MC9151, Los Angeles, CA 90033 USA. EM holschne@usc.edu FU Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VARRD) [B5089R]; VARR&D Research Career Scientist award (OUS) FX This study was supported by a Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VARR&D) #B5089R and a VARR&D Research Career Scientist award (OUS). NR 93 TC 6 Z9 6 U1 0 U2 3 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 JUN PY 2013 VL 30 IS 11 BP 907 EP 919 DI 10.1089/neu.2012.2657 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 166WD UT WOS:000320589300002 PM 23343118 ER PT J AU Durazzo, TC Abadjian, L Kincaid, A Bilovsky-Muniz, T Boreta, L Gauger, GE AF Durazzo, Timothy C. Abadjian, Linda Kincaid, Adam Bilovsky-Muniz, Tobias Boreta, Lauren Gauger, Grant E. TI The Influence of Chronic Cigarette Smoking on Neurocognitive Recovery after Mild Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE cigarette smoking; cognition; mild traumatic brain injury; recovery ID ALCOHOL-DEPENDENT INDIVIDUALS; OXIDATIVE STRESS; NICOTINE ADDICTION; ANTIOXIDANT STATUS; TOBACCO-SMOKE; TEENAGE GIRLS; VITAMIN-C; IN-VITRO; HISTORY; DAMAGE AB The majority of the approximately 1.7 million civilians in the United States who seek emergency care for traumatic brain injury (TBI) are classified as mild (MTBI). Premorbid and comorbid conditions that commonly accompany MTBI may influence neurocognitive and functional recovery. This study assessed the influence of chronic smoking and hazardous alcohol consumption on neurocognitive recovery after MTBI. A comprehensive neurocognitive battery was administered to 25 non-smoking MTBI participants (nsMTBI), 19 smoking MTBI (sMTBI) 38 +/- 22 days (assessment point 1: AP1) and 230 +/- 36 (assessment point 2: AP2) days after injury. Twenty non-smoking light drinkers served as controls (CON). At AP1, nsMTBI and sMTBI were inferior to CON on measures of auditory-verbal learning and memory; nsMTBI performed more poorly than CON on processing speed and global neurocognition, and sMTBI performed worse than CON on working memory measures; nsMTBI were inferior to sMTBI on visuospatial memory. Over the AP1-AP2 interval, nsMTBI showed significantly greater improvement than sMTBI on measures of processing speed, visuospatial learning and memory, visuospatial skills, and global neurocognition, whereas sMTBI only showed significant improvement on executive skills. At AP2, sMTBI remained inferior to CON on auditory-verbal learning and auditory-verbal memory; there were no significant differences between nsMTBI and CON or among nsMTBI and sMTBI on any domain at AP2. Hazardous alcohol consumption was not significantly associated with change in any neurocognitive domain. For sMTBI, over the AP1-AP2 interval, greater lifetime duration of smoking and pack-years were related to significantly less improvement on multiple domains. Results suggest consideration of the effects of chronic cigarette smoking is necessary to understand the potential factors influencing neurocognitive recovery after MTBI. C1 [Durazzo, Timothy C.; Abadjian, Linda; Bilovsky-Muniz, Tobias; Boreta, Lauren; Gauger, Grant E.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Durazzo, Timothy C.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Kincaid, Adam; Gauger, Grant E.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 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 FU Department of Defense [W81XWII-05-2-0094]; National Institute on Drug Abuse [DA24136]; National Institute on Alcohol and Alcoholism [AA10788] FX This material is the result of work supported by the Department of Defense (W81XWII-05-2-0094 to TCD and GEG), National Institute on Drug Abuse (DA24136 to TCD), National Institute on Alcohol and Alcoholism (AA10788 to Dieter J. Meyerhoff), and with resources and the use of facilities at the San Francisco Veterans Affairs Medical Center, San Francisco, CA. We thank Dr. Geoffrey Manley and Michelle Meeker for invaluable assistance in recruitment, Hana Lee for assistance with neurocognitive assessment, and Dr. Dieter J. Meyerhoff for providing a portion of the neurocognitive data for control participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 74 TC 5 Z9 5 U1 0 U2 9 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 JUN PY 2013 VL 30 IS 11 BP 1013 EP 1022 DI 10.1089/neu.2012.2676 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 166WD UT WOS:000320589300012 PM 23421788 ER PT J AU Dreyer, KJ Dreyer, JL AF Dreyer, Keith J. Dreyer, Jonathon L. TI Imaging Informatics: Lead, Follow, or Become Irrelevant SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Dreyer, Keith J.; Dreyer, Jonathon L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dreyer, KJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St, Boston, MA 02114 USA. EM kdreyer@partners.org NR 5 TC 3 Z9 3 U1 2 U2 2 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 JUN PY 2013 VL 10 IS 6 BP 394 EP 396 DI 10.1016/j.jacr.2012.11.011 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 168EK UT WOS:000320688300003 PM 23735267 ER PT J AU Lalani, T Couto, CA Rosen, MP Baker, ME Blake, MA Cash, BD Fidler, JL Greene, FL Hindman, NM Katz, DS Kaur, H Miller, FH Qayyum, A Small, WC Sudakoff, GS Yaghmai, V Yarmish, GM Yee, J AF Lalani, Tasneem Couto, Corey A. Rosen, Max P. Baker, Mark E. Blake, Michael A. Cash, Brooks D. Fidler, Jeff L. Greene, Frederick L. Hindman, Nicole M. Katz, Douglas S. Kaur, Harmeet Miller, Frank H. Qayyum, Aliya Small, William C. Sudakoff, Gary S. Yaghmai, Vahid Yarmish, Gail M. Yee, Judy TI ACR Appropriateness Criteria Jaundice SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; jaundice; cholelithiasis; cholangitis; biliary tract; pancreatic malignancy ID BILE-DUCT STONES; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; MAGNETIC-RESONANCE CHOLANGIOPANCREATOGRAPHY; ROW COMPUTED-TOMOGRAPHY; MR CHOLANGIOPANCREATOGRAPHY; HILAR CHOLANGIOCARCINOMA; PREOPERATIVE EVALUATION; DIRECT CHOLANGIOGRAPHY; OBSTRUCTIVE-JAUNDICE; SUSPECTED CHOLEDOCHOLITHIASIS AB A fundamental consideration in the workup of a jaundiced patient is the pretest probability of mechanical obstruction. Ultrasound is the first-line modality to exclude biliary tract obstruction. When mechanical obstruction is present, additional imaging with CT or MRI can clarify etiology, define level of obstruction, stage disease, and guide intervention. When mechanical obstruction is absent, additional imaging can evaluate liver parenchyma for fat and iron deposition and help direct biopsy in cases where underlying parenchymal disease or mass is found. Imaging techniques are reviewed for the following clinical scenarios: (1) the patient with painful jaundice, (2) the patient with painless jaundice, and (3) the patient with a nonmechanical cause for jaundice. The ACR 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 [Lalani, Tasneem] Inland Imaging Associates, Seattle, WA USA. [Lalani, Tasneem] Univ Washington, Seattle, WA 98195 USA. [Couto, Corey A.] Spectrum Med Grp, South Portland, ME USA. [Rosen, Max P.] UMass Mem Med Sch, Worcester, MA USA. [Rosen, Max P.] UMass Sch Med, Worcester, MA USA. [Baker, Mark E.] Cleveland Clin, Cleveland, OH 44106 USA. [Blake, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cash, Brooks D.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Cash, Brooks D.] Amer Gastroenterol Assoc, Bethesda, MD USA. [Fidler, Jeff L.] Mayo Clin, Rochester, MN USA. [Greene, Frederick L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Hindman, Nicole M.] NYU, Med Ctr, New York, NY 10016 USA. [Katz, Douglas S.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Kaur, Harmeet] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Miller, Frank H.] Northwestern Univ, Feinberg Sch Med NMH, Chicago, IL 60611 USA. [Qayyum, Aliya; Yee, Judy] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Small, William C.] Emory Univ, Atlanta, GA 30322 USA. [Sudakoff, Gary S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Yaghmai, Vahid] Northwestern Univ, Chicago, IL 60611 USA. [Yarmish, Gail M.] Staten Isl Univ Hosp, Staten Isl, NY USA. RP Lalani, T (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM tlalani@inlandimaging.com OI Hindman, Nicole/0000-0003-4762-8041 NR 46 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2013 VL 10 IS 6 BP 402 EP 409 DI 10.1016/j.jacr.2013.02.020 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 168EK UT WOS:000320688300008 PM 23632132 ER PT J AU Ghoshhajra, BB Lee, AM Ferencik, M Elmariah, S Margey, RJP Onuma, O Panagia, M Abbara, S Hoffmann, U AF Ghoshhajra, Brian B. Lee, Ashley M. Ferencik, Maros Elmariah, Sammy Margey, Ronan J. P. Onuma, Oyere Panagia, Marcello Abbara, Suhny Hoffmann, Udo TI Interpreting the Interpretations: The Use of Structured Reporting Improves Referring Clinicians' Comprehension of Coronary CT Angiography Reports SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Structured reporting; coronary CT angiography; referring clinicians ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ACUTE CHEST-PAIN; PROGNOSTIC VALUE; ARTERY-DISEASE; COMMUNICATION; METAANALYSIS; MORTALITY; OUTCOMES AB Background: Efficiency of coronary CT angiography (CCTA) in clinical practice depends on precise reporting and accurate result interpretation. Objective: We sought to assess referring clinicians' understanding of patients' coronary artery disease (CAD) severity and to compare satisfactions of the free-form impression (FFI) with satisfactions of the structured impression (SI section of CCTA reports. Materials and Methods: Fifty clinical CCTA reports from May 2011 to April 2012 were retrospectively selected (25 FFI and 25 SI), to include cases with the entire spectrum of CAD (6 categories encompassing normal, minimal, mild, moderate, severe stenosis, and occlusion). A survey containing only randomized blinded impressions was distributed to 4 cardiologists and 2 cardiac imaging specialists. Clinician interpretation was examined regarding (Q1) worst stenosis severity, (Q2) number of vessels with significant stenosis, and (Q3) the presence of nonevaluable segments. Agreement proportions and Cohen's kappa were evaluated between FFI versus SI. Satisfactions were measured with respect to content, clarity, and clinical effectiveness. Results: Q1 agreement was excellent for both FFI and SI (by 6 categories: 80% versus 85%; P > .05; kappa: 0.87 versus 0.89; by no CAD versus nonsignificant versus significant CAD: 99% versus 97%; P > .05; kappa: 0.99 versus 0.94). Q2 agreement improved from fair to moderate (53% versus 68%; P = .04; kappa 0.31 versus 0.52). Q3 agreement was moderate (90% versus 87%; P > .05; kappa 0.57 versus 0.58). Satisfactions with impressions were high and similar for FFI and SI for clinicians. Conclusion: Structured impressions were shown to improve result interpretation agreement from fair to moderate with regard to the number of vessels with significant stenosis. C1 [Lee, Ashley M.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Lee, Ashley M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lee, Ashley M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, AM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM amlee@partners.org FU NHLBI NIH HHS [T32 HL076136] NR 24 TC 9 Z9 9 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 JUN PY 2013 VL 10 IS 6 BP 432 EP 438 DI 10.1016/j.jacr.2012.11.012 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 168EK UT WOS:000320688300012 PM 23485747 ER PT J AU Ahmed, FS Miller, LS AF Ahmed, Fayeza S. Miller, L. Stephen TI Relationship Between Theory of Mind and Functional Independence Is Mediated by Executive Function SO PSYCHOLOGY AND AGING LA English DT Article DE theory of mind; executive function; functional independence ID MILD COGNITIVE IMPAIRMENT; STRANGE STORIES TEST; OLDER-ADULTS; ASPERGER-SYNDROME; FRONTOTEMPORAL DEMENTIA; INSTRUMENTAL ACTIVITIES; ALZHEIMERS-DISEASE; INHIBITORY CONTROL; WORKING-MEMORY; MENTAL-STATE AB Theory of mind (ToM) is the ability to comprehend another person's perspective. Although there is much literature of ToM in children, there is a limited and somewhat inconclusive amount of studies examining ToM in a geriatric population. This study examined ToM's relationship to functional independence. Two tests of ToM, tests of executive function, and a measure of functional ability were administered to cognitively intact older adults. Results showed that 1 test of ToM (Strange Stories test) significantly accounted for variance in functional ability, whereas the other did not (Faux Pas test). In addition, Strange Stories test performance was partially driven by a verbal abstraction-based executive function: proverb interpretation. A multiple mediation model was employed to examine whether executive functions explained the relationship between the Strange Stories test and functional ability. Results showed that both the combined and individual indirect effects of the executive function measures mediated the relationship. We argue that, although components of ToM are associated with functional independence, ToM does not appear to account for additional variance in functional independence beyond executive function measures. C1 [Ahmed, Fayeza S.; Miller, L. Stephen] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. RP Ahmed, FS (reprint author), VA Puget Sound, Seattle, WA USA. EM ahmedfs@gmail.com NR 95 TC 2 Z9 2 U1 8 U2 30 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD JUN PY 2013 VL 28 IS 2 BP 293 EP 303 DI 10.1037/a0031365 PG 11 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 165OB UT WOS:000320492100001 PM 23795763 ER PT J AU Miao, J Wang, SB Park, WM Xia, Q Fang, XT Torriani, MP Wood, KB Li, GA AF Miao, Jun Wang, Shaobai Park, Won Man Xia, Qun Fang, Xiutong Torriani, Martin P. Wood, Kirkham B. Li, Guoan TI Segmental spinal canal volume in patients with degenerative spondylolisthesis SO SPINE JOURNAL LA English DT Article DE Lumbar degenerative spondylolisthesis; Spinal canal volume; Kinematics; Lumbar spine; Fluoroscopy ID LUMBAR SPINE; ASYMPTOMATIC INDIVIDUALS; SURGICAL-TREATMENT; INTERBODY FUSION; STENOSIS; ALIGNMENT; POSITION; TRENDS; IMAGE; ANGLE AB BACKGROUND CONTEXT: Lumbar degenerative spondylolisthesis (DS), typically characterized by the forward slippage of the superior vertebra of a lumbar motion segment, is a common spinal pathological condition in elderly individuals. Significant deformation and volume changes of the spinal canal can occur because of the vertebral slippage, but few data have been reported on these anatomic variations in DS patients. Whether to restore normal anatomy, such as reduction of the slippage and restoration of disc height, is still not clear in surgery. PURPOSE: This study was designed to determine the volume change of the spinal canal and detect specific anatomic factors affecting the spinal canal volume in DS patients. STUDY DESIGN/SETTING: A case-control study. METHODS: Nine asymptomatic volunteers (mean age 54.4) and 9 patients with L4/L5 DS (mean age 73.4) were recruited. All patients had intermittent claudication and different extent low back pain, and two patients also had leg pain. L4/L5 vertebral motion segment unit of each subject was reconstructed using three-dimensional computed tomography or magnetic resonance images in a solid modeling software. In vivo lumbar vertebral motion during functional postures (supine, standing upright, flexion, and extension) was determined using a dual fluoroscopic imaging technique. The volume of the spinal canal was measured at each functional posture. Various anatomic parameters (disc height, cross-sectional area of the canal, left-right diameter of the canal, anterior-posterior diameter of the canal, slippage, posture, intervertebral disc angle [ DA], etc.) that may potentially affect the canal volume were also measured, and their correlations with the volume change of spinal canal were analyzed. This study was funded by a 2-year, $275,000 grant from the National Institutes of Health. RESULTS: On average, spinal canal volume was larger at supine and flexion postures than at stand and extension postures in both the DS and the asymptomatic groups. Spinal canal volume of the DS patients were significantly lower than that of the asymptomatic subjects under all the four postures (p<.05). Correlation analysis showed that spinal canal volume was strongly affected by the posterior disc height (Pearson correlation coefficient gamma(b)=0.822) and the slippage percentage (gamma(b)=-0.593) and moderately affected by the anterior disc height (gamma(b)=0.300) and the DA (gamma(b)=-0.237). CONCLUSIONS: The volume of spinal canal is affected by multiple factors. Increased spinal canal volume at supine and flexion positions may explain the clinical observations of relief of symptoms at these postures in DS patients. The data also suggest that reduction of slipped vertebral body, decrease of DA, intervertebral distraction, and decompression could all be effective to increase the canal volume of DS patients thus to relieve clinical symptoms. (C) 2013 Elsevier Inc. All rights reserved. C1 [Miao, Jun; Wang, Shaobai; Park, Won Man; Fang, Xiutong; Torriani, Martin P.; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Miao, Jun; Xia, Qun] Tianjin Hosp, Dept Spinal Surg, Tianjin 300210, Peoples R China. [Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Park, Won Man] Kyung Hee Univ, Dept Mech Engn, Yongin 446701, South Korea. [Fang, Xiutong] Beijing Capital Med Univ, Beijing Shijitan Hosp, Dept Orthoped, Beijing 100038, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partner.org FU National Institutes of Health [R21AR057989]; NASS (North American Spine Society); SRS (Scoliosis Research Society); China Scholarship Council [2009912008] FX This study was supported by National Institutes of Health (R21AR057989), NASS (North American Spine Society), SRS (Scoliosis Research Society), and China Scholarship Council (2009912008). NR 30 TC 8 Z9 11 U1 4 U2 6 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 JUN PY 2013 VL 13 IS 6 BP 706 EP 712 DI 10.1016/j.spinee.2013.02.017 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 166XY UT WOS:000320595200015 PM 23541448 ER PT J AU Grabowski, EF Kushak, RI Liu, BH Ingelfinger, JR AF Grabowski, Eric F. Kushak, Rafail I. Liu, Bohan Ingelfinger, Julie R. TI Shiga toxin downregulates tissue factor pathway inhibitor, modulating an increase in the expression of functional tissue factor on endothelium SO THROMBOSIS RESEARCH LA English DT Article DE Endothelial cells; Hemolytic uremic syndrome (HUS); Shiga toxin (Stx); Tissue factor (TF); Tissue factor pathway inhibitor (TFPI) ID HEMOLYTIC-UREMIC SYNDROME; TUMOR-NECROSIS-FACTOR; ESCHERICHIA-COLI; CELLS; ALPHA; PATHOGENESIS; VEROTOXIN; RECEPTOR; IDENTIFICATION; CYTOKINES AB Introduction: Endothelial expression of tissue factor (TF) may play a major role in (Stx)-related hemolytic uremic syndrome. We examined human umbilical vein endothelial cell (HUVEC) monolayers to determine the interaction between TF and TF pathway inhibitor (TFPI), hypothesizing that changes in TFPI modulate TF expression. Materials and Methods: We studied 1) cell surface expression of globotriasylceramide (Gb3, the receptor for Stx) with Stx-1 (10 pM), TNF alpha (20 Ng/ml), or Stx-1 plus TNFa compared to control, 2) gene expression of TF and TFPI, 3) total cellular and cell surface antigenic TF and TFPI, 4) TFPI secretion into supernatant, and 5) factor Xa production. Results and Conclusions: Gb3 expression, negligible with control and Stx-1 alone, increased significantly with TNFa and with Stx-1 plus TNF alpha. TF mRNA increased 1.25 +/- 0.32-fold (N = 9; p = 0.041) with Stx-1 alone vs. 2.82 +/- 0.92-fold (N = 13; p < 0.0005) with TNFa alone. However, Stx-1 plus TNFa yielded a 6.51 +/- 3.48-fold increase (N = 17; p < 0.0005). TFPI mRNA decreased with TNFa (p < 0.001) and Stx-1 plus TNF alpha (p < 0.0005). Total cellular and cell surface TF antigen increased significantly with TNF alpha, but no further with Stx-1 plus TNF alpha. Total TFPI cellular and cell surface antigen levels, and TFPI secretion decreased significantly with Stx-1 plus TNF alpha. Median factor Xa production for Stx-1 plus TNF alpha vs TNF alpha alone increased (p < 0.001) 3.24-fold. Our results indicate that a subinhibitory concentration of Stx-1 plus TNFa impairs TFPI gene expression, synthesis, cell-surface association, and secretion, leading to augmented functional TF. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Grabowski, Eric F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grabowski, EF (reprint author), Massachusetts Gen Hosp, Yawkey 8B,55 Fruit St, Boston, MA 02114 USA. EM Grabowski.Eric@MGH.Harvard.edu FU NHLBI [R01HL089332] FX This work was supported by NHLBI R01HL089332, "Tissue Factor, Flow, and Platelet Adhesion/Aggregation on Activated Endothelium." EG, RK, and JI designed the experiments and wrote the paper, while EG and RK directed and conducted the experiments. BL performed special data analysis and Figure revision. We thank Kylee Yam, Ming Cheung, Emily Bilouris, and Amy Skaria for expert technical help with the experiments and data analysis. We are grateful to Brian Healy of the MGH Biostatistics Center for help with the statistical analyses. NR 35 TC 4 Z9 5 U1 1 U2 7 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 JUN PY 2013 VL 131 IS 6 BP 521 EP 528 DI 10.1016/j.thromres.2013.03.006 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 166ZI UT WOS:000320599400022 PM 23642803 ER PT J AU Morinelli, TA Lee, MH Kendall, RT Luttrell, LM Walker, LP Ullian, ME AF Morinelli, Thomas A. Lee, Mi-Hye Kendall, Ryan T. Luttrell, Louis M. Walker, Linda P. Ullian, Michael E. TI Angiotensin II activates NF-kappa B through AT(1A) receptor recruitment of beta-arrestin in cultured rat vascular smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE angiotensin receptor; NF-kappa B; beta-arrestins; signal transduction; vascular smooth muscle cells; cyclooxygenase-2 ID NUCLEAR-LOCALIZATION SEQUENCE; SIGNAL-TRANSDUCTION; TYROSINE KINASES; EXPRESSION; PATHWAY; CYCLOOXYGENASE-2; IDENTIFICATION; TRANSCRIPTION; PHOSPHORYLATION; MOLECULE AB Activation of the angiotensin type 1A receptor (AT(1A)R) in rat aorta vascular smooth muscle cells (RASMC) results in increased synthesis of the proinflammatory enzyme cyclooxygenase-2 (COX-2). We previously showed that nuclear localization of internalized AT(1A)R results in activation of transcription of the gene for COX-2, i.e., prostaglandin-endoperoxide synthase-2. Others have suggested that ANG II stimulation of COX-2 protein synthesis is mediated by NF-kappa B. The purpose of the present study was to examine the interrelationship between AT(1A)R activation, beta-arrestin recruitment, and NF-kappa B activation in the ability of ANG II to increase COX-2 protein synthesis in RASMC. In the present study we utilized RASMC, inhibitors of the NF-kappa B pathway, beta-arrestin knockdown, radioligand binding, immunoblotting, and immunofluorescence to characterize the roles of AT(1A)R internalization, NF-kappa B activation, and beta-arrestin in ANG II-induced COX-2 synthesis. Ro-106-9920 or parthenolide, agents that inhibit the initial steps of NF-kappa B activation, blocked ANG II-induced p65 NF-kappa B nuclear localization, COX-2 protein expression, beta-arrestin recruitment, and AT(1A)R internalization without inhibiting ANG II-induced p42/44 ERK activation. Curcumin, an inhibitor of NF-kappa B-induced transcription, blocked ANG II-induced COX-2 protein expression without altering AT(1A)R internalization, ANG II-induced p65 NF-kappa B nuclear localization, or p42/44 ERK activation. Small interfering RNA-induced knockdown of beta-arrestin-1 and -2 inhibited ANG II-induced p65 NF-kappa B nuclear localization. In vascular smooth muscle cells, internalization of the activated AT(1A)R mediated by beta-arrestins activates the NF-kappa B pathway, producing nuclear localization of the transcription factor and initiation of COX-2 protein synthesis, thereby linking internalization of the receptor with the NF-kappa B pathway. C1 [Morinelli, Thomas A.; Walker, Linda P.; Ullian, Michael E.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Lee, Mi-Hye; Kendall, Ryan T.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. [Luttrell, Louis M.; Ullian, Michael E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Morinelli, TA (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,MSC 629, Charleston, SC 29425 USA. EM morinelt@musc.edu FU Dialysis Clinic, Incorporated; National Institute of Diabetes and Digestive and Kidney Diseases [DK-055524]; National Center for Research Resources [1S10 RR-027777-01]; Research Service of the Veterans Affairs Medical Center of Charleston, SC FX This project was supported by Dialysis Clinic, Incorporated, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-055524 (L. M. Luttrell), National Center for Research Resources Grant 1S10 RR-027777-01 (FLIPR Tetra, L. M. Luttrell and T. A. Morinelli), and the Research Service of the Veterans Affairs Medical Center of Charleston, SC. NR 33 TC 7 Z9 7 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2013 VL 304 IS 12 BP C1176 EP C1186 DI 10.1152/ajpcell.00235.2012 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 164XJ UT WOS:000320445300009 PM 23576578 ER PT J AU Miller, MW Knaub, LA Olivera-Fragoso, LF Keller, AC Balasubramaniam, V Watson, PA Reusch, JEB AF Miller, Matthew W. Knaub, Leslie A. Olivera-Fragoso, Luis F. Keller, Amy C. Balasubramaniam, Vivek Watson, Peter A. Reusch, Jane E. B. TI Nitric oxide regulates vascular adaptive mitochondrial dynamics SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE endothelial nitric oxide synthase; vascular mitochondria ID SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; SUPEROXIDE-DISMUTASE; DIABETES-MELLITUS; OXIDATIVE STRESS; SKELETAL-MUSCLE; PULMONARY-HYPERTENSION; IN-VIVO; DYSFUNCTION; SYNTHASE AB Cardiovascular disease risk factors, such as diabetes, hypertension, dyslipidemia, obesity, and physical inactivity, are all correlated with impaired endothelial nitric oxide synthase (eNOS) function and decreased nitric oxide (NO) production. NO-mediated regulation of mitochondrial biogenesis has been established in many tissues, yet the role of eNOS in vascular mitochondrial biogenesis and dynamics is unclear. We hypothesized that genetic eNOS deletion and 3-day nitric oxide synthase (NOS) inhibition in rodents would result in impaired mitochondrial biogenesis and defunct fission/fusion and autophagy profiles within the aorta. We observed a significant, eNOS expression-dependent decrease in mitochondrial electron transport chain (ETC) protein subunits from complexes I, II, III, and V in eNOS heterozygotes and eNOS null mice compared with age-matched controls. In response to NOS inhibition with N-G-nitro-L-arginine methyl ester (L-NAME) treatment in Sprague Dawley rats, significant decreases were observed in ETC protein subunits from complexes I, III, and IV as well as voltage-dependent anion channel 1. Decreased protein content of upstream regulators of mitochondrial biogenesis, cAMP response element-binding protein and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, were observed in response to 3-day L-NAME treatment. Both genetic eNOS deletion and NOS inhibition resulted in decreased manganese superoxide dismutase protein. L-NAME treatment resulted in significant changes to mitochondrial dynamic protein profiles with decreased fusion, increased fission, and minimally perturbed autophagy. In addition, L-NAME treatment blocked mitochondrial adaptation to an exercise intervention in the aorta. These results suggest that eNOS/NO play a role in basal and adaptive mitochondrial biogenesis in the vasculature and regulation of mitochondrial turnover. C1 [Miller, Matthew W.; Knaub, Leslie A.; Keller, Amy C.; Balasubramaniam, Vivek; Watson, Peter A.; Reusch, Jane E. B.] Univ Colorado, Aurora, CO USA. [Miller, Matthew W.; Knaub, Leslie A.; Keller, Amy C.; Watson, Peter A.; Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Olivera-Fragoso, Luis F.] Univ Puerto Rico, San Juan, PR 00936 USA. [Balasubramaniam, Vivek] Childrens Hosp, Aurora, CO USA. RP Reusch, JEB (reprint author), Univ Colorado Denver, Div Endocrinol Diabet & Metab, Anschutz Med Campus,12801 E 17th Ave,MS8106, Aurora, CO 80045 USA. EM jane.reusch@ucdenver.edu FU National Heart, Lung, and Blood Institute [1R25-HL-103286-02] FX This work was supported by National Heart, Lung, and Blood Institute Grant 1R25-HL-103286-02. NR 68 TC 22 Z9 24 U1 2 U2 27 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 JUN PY 2013 VL 304 IS 12 BP H1624 EP H1633 DI 10.1152/ajpheart.00987.2012 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 164XB UT WOS:000320444300004 PM 23585138 ER PT J AU Trivedi, MH Morris, DW Wisniewski, SR Lesser, I Nierenberg, AA Daly, E Kurian, BT Gaynes, BN Balasubramani, GK Rush, AJ AF Trivedi, Madhukar H. Morris, David W. Wisniewski, Stephen R. Lesser, Ira Nierenberg, Andrew A. Daly, Ella Kurian, Benji T. Gaynes, Bradley N. Balasubramani, G. K. Rush, A. John TI Increase in Work Productivity of Depressed Individuals With Improvement in Depressive Symptom Severity SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; MEASUREMENT-BASED CARE; ILLNESS RATING-SCALE; FORM HEALTH SURVEY; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; CLINICAL-PRACTICE AB Objective: The authors sought to identify baseline clinical and sociodemographic characteristics associated with work productivity in depressed outpatients and to assess the effect of treatment on work productivity. Method: Employed depressed outpatients 18-75 years old who completed the Work Productivity and Activity Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial (level 1), either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided (level 2). Participants' clinical "and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time. Results: Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all independently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression. Conclusions: Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to persistent impairment in occupational productivity, implying a need for additional, possibly novel, treatments. C1 [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75235 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Calif Los Angeles, Dept Psychiat, Geffen Sch Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75235 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU Abbott Laboratories; Abdi Ibrahim; Agency for Healthcare Research and Quality; Akzo (Organon Pharmaceuticals); Alkermes; AstraZeneca; Axon Advisors; Bristol-Myers Squibb; Cephalon; Corcept Therapeutics; Cyberonics; Eli Lilly; Evotec; Fabre Kramer Pharmaceuticals; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products; Johnson Johnson PRD; Libby; Lundbeck; Mead Johnson; MedAvante; Medtronic; Merck; National Institute on Drug Abuse; NARSAD; Naurex; Neuronetics; NIMH; Novartis; Otsuka Pharmaceuticals; Pamlab; Parke-Davis Pharmaceuticals; Pfizer; PgxHealth; Pharmacia Upjohn; Predix Pharmaceuticals (Epix); Rexahn Pharmaceuticals; Roche Products; Sepracor; Shire Development; Sierra; SK Life and Science; Solvay Pharmaceuticals; Takeda; Transcept; Vantage Point; Wyeth-Ayerst Laboratories; Basilea Pharmaceutica; Brain Cells; Cederroth; Dainippon Sumitomo; EpiQ; Genaissance; Janssen Pharmaceutica; Jazz Pharmaceuticals; Innapharma; Lichtwer Pharma; Massachusetts General Psychiatry Academy; Janssen Pharmaceuticals; Johnson Johnson; Rexahn; Targacept; M-3 Corporation; Robert Wood Johnson Foundation; Shire Pharmaceuticals; Wyeth-Ayerst; Duke-National University of Singapore Graduate Medical School; Brain Resource; Otsuka; University of Michigan; Singapore College of Family Physicians; NIMH [N01MH90003] FX Dr. Trivedi has received research support from or served as an adviser, consultant, or speaker for Abbott Laboratories, Abdi Ibrahim, Agency for Healthcare Research and Quality, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Corcept Therapeutics, Cyberonics, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Mead Johnson, MedAvante, Medtronic, Merck, National Institute on Drug Abuse, NARSAD, Naurex, Neuronetics, NIMH, Novartis, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), Rexahn Pharmaceuticals, Roche Products, Sepracor, Shire Development, Sierra, SK Life and Science, Solvay Pharmaceuticals, Takeda, Transcept, Vantage Point, and Wyeth-Ayerst Laboratories. Dr. Wisniewski has served as a consultant for Dey Pharmaceuticals and Venebio and has received grant support from Eli Lilly. Dr. Lesser has received grant support from NIMH. Dr. Nierenberg has received research support from or served as an adviser, consultant, or speaker for AstraZeneca, Basilea Pharmaceutica, Brain Cells, Bristol-Myers Squibb, Cederroth, Cyberonics, Dainippon Sumitomo, Eli Lilly, EpiQ, Forest Pharmaceuticals, Genaissance, GlaxoSmithKline, Janssen Pharmaceutica, Jazz Pharmaceuticals, Innapharma, Lichtwer Pharma, Eli Lilly, Merck, Neuronetics, Novartis, Organon, Pamlab, Pfizer, PGx Health, NIMH, NARSAD, Sepracor, Shire, Stanley Foundation, Targacept, Takeda, Wyeth-Ayerst Laboratories, and Massachusetts General Psychiatry Academy (MGHPA talks are supported through Independent Medical Education grants from AstraZeneca, Eli Lilly, and Janssen Pharmaceuticals); he has equity holdings (excluding mutual funds/blind trusts) in Appliance Computing. Dr. Daly is currently a full-time employee and stockholder of Johnson & Johnson PRD; at the time of this study, she was an assistant professor at the University of Texas Medical Center, Dallas, where she continues to hold a position as adjunct faculty. Dr. Kurian has received research grant support from Evotec, Forest Pharmaceuticals, Johnson & Johnson, Naurex, NIMH, Pfizer, Rexahn, and Targacept. Dr. Gaynes has received research support from or served as an adviser, consultant, or speaker for the Agency for Healthcare Research and Quality, Bristol-Myers Squibb, GlaxoSmithKline, M-3 Corporation, NImH, Novartis, Ovation Pharmaceuticals, Pfizer, Robert Wood Johnson Foundation, Shire Pharmaceuticals, and Wyeth-Ayerst. Dr. Rush has received research support from Duke-National University of Singapore Graduate Medical School and NIMH; consulting fees from Brain Resource, Otsuka, and University of Michigan; speaking fees from Singapore College of Family Physicians; royalties from Guilford Publications and the University of Texas Southwestern Medical Center; and travel support from Collegium Internationale Neuro-PsychoPharmacologicum. The other authors report no financial relationships with commercial interests.; Supported by NIMH contract N01MH90003 to University of Texas Southwestern Medical Center at Dallas (principal investigator, Dr. Rush). Medications for this trial were provided at no cost by Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth. NR 39 TC 24 Z9 24 U1 0 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2013 VL 170 IS 6 BP 633 EP 641 DI 10.1176/appi.ajp.2012.12020250 PG 9 WC Psychiatry SC Psychiatry GA 159VG UT WOS:000320074800013 PM 23558394 ER PT J AU Merkow, RP Bentrem, DJ Winchester, DP Stewart, AK Ko, CY Bilimoria, KY AF Merkow, Ryan P. Bentrem, David J. Winchester, David P. Stewart, Andrew K. Ko, Clifford Y. Bilimoria, Karl Y. TI Effect of Including Cancer-Specific Variables on Risk-Adjusted Hospital Surgical Quality Comparisons SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Endocrine Cancer Parallel Session at the 65th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) / Presidential Plenary Session CY MAR 21-24, 2012 CL Orlando, FL SP Soc Surg Oncol (SSO) ID IMPROVEMENT PROGRAM; SURGERY; MORTALITY; SAFETY; CARE AB Quality initiatives are increasingly focusing on the quality of oncologic surgery. However, there is concern that a lack of cancer-specific variables may make risk-adjusted hospital quality comparisons inadequate. Our objective was to assess whether hospital quality rankings for cancer surgery are influenced by the addition of cancer-specific variables to the risk-adjusted models. Patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and National Cancer Data Base (NCDB) who underwent colon or rectal resection for cancer were linked (2006-2008). Hierarchical models were developed predicting ACS NSQIP outcomes based on ACS NSQIP only vs a model using NSQIP and NCDB-derived cancer variables (e.g., stage and neoadjuvant therapy). Changes in hospital quality rankings were compared. A total of 11,405 patients underwent colon (n = 9,678, 146 hospitals) or rectal (n = 1,727, 135 hospitals) resection for cancer (2006-2008). Hospital-level complication rates (and standard deviation) after colon surgery were 2.2 % (+/- 2.7 %) for mortality and 17.2 % (+/- 8.7 %) for serious morbidity. After rectal cancer resection, complication rates were 0.9 % (+/- 3.8 %) for mortality and 22.3 % (+/- 20.4 %) for serious morbidity. When cancer-specific variables were included in risk-adjustment, outlier agreement was very good (kappa > 0.85), and hospital odds ratio correlations were nearly identical (R > 0.98) for all outcomes assessed. Median changes in hospital rankings with the addition of the cancer-specific variables ranged from 1 to 2 after colon resection to 2-4 after rectal resection. Addition of the available cancer-specific variables to risk-adjustment models did not affect hospital quality rankings for cancer surgery. Existing ACS NSQIP risk-adjustment variables appears to be sufficient for accurate comparisons of hospital quality. C1 [Merkow, Ryan P.; Winchester, David P.; Stewart, Andrew K.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Northwestern Inst Comparat Effectiveness Res NICE, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado Denver, Dept Surg, Aurora, CO USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. EM kbilimoria@facs.org NR 18 TC 6 Z9 6 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 JUN PY 2013 VL 20 IS 6 BP 1766 EP 1773 DI 10.1245/s10434-013-2867-z PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 147LS UT WOS:000319169100004 PM 23354565 ER PT J AU Win, AK Parry, S Parry, B Kalady, MF Macrae, FA Ahnen, DJ Young, GP Lipton, L Winship, I Boussioutas, A Young, JP Buchanan, DD Arnold, J Le Marchand, L Newcomb, PA Haile, RW Lindor, NM Gallinger, S Hopper, JL Jenkins, MA AF Win, Aung Ko Parry, Susan Parry, Bryan Kalady, Matthew F. Macrae, Finlay A. Ahnen, Dennis J. Young, Graeme P. Lipton, Lara Winship, Ingrid Boussioutas, Alex Young, Joanne P. Buchanan, Daniel D. Arnold, Julie Le Marchand, Loic Newcomb, Polly A. Haile, Robert W. Lindor, Noralane M. Gallinger, Steven Hopper, John L. Jenkins, Mark A. TI Risk of Metachronous Colon Cancer Following Surgery for Rectal Cancer in Mismatch Repair Gene Mutation Carriers SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; POUCH-ANAL ANASTOMOSIS; QUALITY-OF-LIFE; LYNCH-SYNDROME; FAMILY AB Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer. This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan-Meier method. During median 9 years (range 1-32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81-37.19 per 1,000 person-years). Cumulative risk of metachronous colon cancer was 19 % (95 % CI 9-31 %) at 10 years, 47 (95 % CI 31-68 %) at 20 years, and 69 % (95 % CI 45-89 %) at 30 years after surgical resection. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01-1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III. Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered. C1 [Win, Aung Ko; Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia. [Parry, Susan; Arnold, Julie] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand. [Parry, Susan] Middlemore Hosp, Dept Gastroenterol, Auckland 6, New Zealand. [Parry, Bryan] Auckland City Hosp, Colorectal Surg Unit, Auckland, New Zealand. [Kalady, Matthew F.] Cleveland Clin, Inst Digest Dis, Dept Colorectal Surg, Cleveland, OH 44106 USA. [Macrae, Finlay A.; Winship, Ingrid] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver VA Med Ctr, Denver, CO 80202 USA. [Young, Graeme P.] Flinders Univ S Australia, Flinders Ctr Innovat Canc, Adelaide, SA 5001, Australia. [Lipton, Lara] Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. [Winship, Ingrid] Univ Melbourne, Dept Med, Parkville, Vic 3052, Australia. [Boussioutas, Alex] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic, Australia. [Boussioutas, Alex] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Boussioutas, Alex] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia. [Young, Joanne P.; Buchanan, Daniel D.] Queensland Inst Med Res, Canc & Populat Studies Grp, Bancroft Ctr, Herston, Qld 4006, Australia. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Haile, Robert W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gallinger, Steven] Canc Care Ontario, Toronto, ON, Canada. RP Win, AK (reprint author), Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia. EM SParry@adhb.govt.nz RI Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Boussioutas, Alex/0000-0002-8109-6897; Win, Aung Ko/0000-0002-2794-5261; Buchanan, Daniel/0000-0003-2225-6675; Winship, Ingrid/0000-0001-8535-6003 FU National Cancer Institute, National Institutes of Health under RFA [CA-95-011]; Picchi Brothers Foundation Cancer Council Victoria Cancer Research Scholarship, Australia FX This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. Collaborating centers include Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799) [USC], Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). AKW is supported by the Picchi Brothers Foundation Cancer Council Victoria Cancer Research Scholarship, Australia. MAJ is a Senior Research Fellow and JLH is an Australia Fellow of the National Health and Medical Research Council, Australia. NR 24 TC 29 Z9 31 U1 0 U2 7 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 JUN PY 2013 VL 20 IS 6 BP 1829 EP 1836 DI 10.1245/s10434-012-2858-5 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 147LS UT WOS:000319169100011 PM 23358792 ER PT J AU In, H Jiang, W Lipsitz, SR Neville, BA Weeks, JC Greenberg, CC AF In, Haejin Jiang, Wei Lipsitz, Stuart R. Neville, Bridget A. Weeks, Jane C. Greenberg, Caprice C. TI Variation in the Utilization of Reconstruction Following Mastectomy in Elderly Women SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID LINEAR MIXED MODELS; BREAST RECONSTRUCTION; COMORBIDITY INDEX; CANCER; SURGERY; DETERMINANTS; POPULATION; DATABASES; IMMEDIATE; REASONS AB Regardless of their age, women who choose to undergo postmastectomy reconstruction report improved quality of life as a result. However, actual use of reconstruction decreases with increasing age. Whereas this may reflect patient preference and clinical factors, it may also represent age-based disparity. Women aged 65 years or older who underwent mastectomy for DCIS/stage I/II breast cancer (2000-2005) were identified in the SEER-Medicare database. Overall and institutional rates of reconstruction were calculated. Characteristics of hospitals with higher and lower rates of reconstruction were compared. Pseudo-RA(2) statistics utilizing a patient-level logistic regression model estimated the relative contribution of institution and patient characteristics. A total of 19,234 patients at 716 institutions were examined. Overall, 6 % of elderly patients received reconstruction after mastectomy. Institutional rates ranged from zero to > 40 %. Whereas 53 % of institutions performed no reconstruction on elderly patients, 5.6 % performed reconstructions on more than 20 %. Although patient characteristics (%Delta RA(2)A = 70 %), and especially age (%Delta RA(2)A = 34 %), were the primary determinants of reconstruction, institutional characteristics also explained some of the variation (%Delta RA(2)A = 16 %). This suggests that in addition to appropriate factors, including clinical characteristics and patient preferences, the use of reconstruction among older women also is influenced by the institution at which they receive care. Variation in the likelihood of reconstruction by institution and the association with structural characteristics suggests unequal access to this critical component of breast cancer care. Increased awareness of a potential age disparity is an important first step to improve access for elderly women who are candidates and desire reconstruction. C1 [In, Haejin; Jiang, Wei; Lipsitz, Stuart R.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [In, Haejin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [In, Haejin] Univ Chicago, Med Ctr, Dept Surg, Chicago, IL 60637 USA. [Neville, Bridget A.; Weeks, Jane C.; Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Greenberg, Caprice C.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, Madison, WI USA. RP In, H (reprint author), Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. EM Haejin.In@uchospitals.edu RI JIANG, WEI /F-3930-2015 FU National Cancer Institute [R25 CA92203] FX This study used the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare database. This resource has been made available to the research community through collaborative efforts of the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS). We acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services; and the SEER Program tumor registries in the creation of the SEER-Medicare database. Haejin In was supported by a National Cancer Institute training grant (R25 CA92203), titled "Program in Cancer Outcomes Research Training". NR 27 TC 17 Z9 17 U1 1 U2 4 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 JUN PY 2013 VL 20 IS 6 BP 1872 EP 1879 DI 10.1245/s10434-012-2821-5 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 147LS UT WOS:000319169100017 PM 23263733 ER PT J AU Svensson, LG Adams, DH Bonow, RO Kouchoukos, NT Miller, DC O'Gara, PT Shahian, DM Schaff, HV Akins, CW Bavaria, JE Blackstone, EH David, TE Desai, ND Dewey, TM D'Agostino, RS Gleason, TG Harrington, KB Kodali, S Kapadia, S Leon, MB Lima, B Lytle, BW Mack, MJ Reardon, M Reece, TB Reiss, GR Roselli, EE Smith, CR Thourani, VH Tuzcu, EM Webb, J Williams, MR AF Svensson, Lars G. Adams, David H. Bonow, Robert O. Kouchoukos, Nicholas T. Miller, D. Craig O'Gara, Patrick T. Shahian, David M. Schaff, Hartzell V. Akins, Cary W. Bavaria, Joseph E. Blackstone, Eugene H. David, Tirone E. Desai, Nimesh D. Dewey, Todd M. D'Agostino, Richard S. Gleason, Thomas G. Harrington, Katherine B. Kodali, Susheel Kapadia, Samir Leon, Martin B. Lima, Brian Lytle, Bruce W. Mack, Michael J. Reardon, Michael Reece, T. Brett Reiss, G. Russell Roselli, Eric E. Smith, Craig R. Thourani, Vinod H. Tuzcu, E. Murat Webb, John Williams, Mathew R. CA Writing Comm Members TI Aortic Valve and Ascending Aorta Guidelines for Management and Quality Measures SO ANNALS OF THORACIC SURGERY LA English DT Article ID PROSTHESIS-PATIENT MISMATCH; COREVALVE REVALVING SYSTEM; VALVULAR HEART-DISEASE; HYPOTHERMIC CIRCULATORY ARREST; LEFT-VENTRICULAR DYSFUNCTION; HIGH-RISK PATIENTS; ANTEGRADE CEREBRAL PERFUSION; LONG-TERM SURVIVAL; EDWARDS SAPIEN VALVE; PROSPECTIVE RANDOMIZED-TRIAL C1 [Svensson, Lars G.] Cleveland Clin, Cleveland, OH 44195 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Cardiac Thoracic & Vasc Surg Inc, St Louis, MO USA. Falk Cardiovasc Res Ctr, Palo Alto, CA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Toronto Gen Hosp, Toronto, ON, Canada. Inst Technol, Dallas, TX USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. Columbia Univ, Med Ctr, New York, NY USA. Baylor Hlth Care Syst, Dallas, TX USA. Methodist Hosp, Houston, TX 77030 USA. Univ Colorado, Boulder, CO 80309 USA. Dean Hlth Syst, Madison, WI USA. Emory Univ, Sch Med, Atlanta, GA USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. RP Svensson, LG (reprint author), Cleveland Clin, 9500 Euclid Ave,Desk F-25 CT Surg, Cleveland, OH 44195 USA. OI Schaff, Hartzell/0000-0003-0994-027X NR 462 TC 37 Z9 39 U1 3 U2 17 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 JUN PY 2013 VL 95 IS 6 SU S BP S1 EP S66 DI 10.1016/j.athoracsur.2013.01.083 PG 66 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 162ZD UT WOS:000320303900001 PM 23688839 ER PT J AU Kanda, M Sadakari, Y Borges, M Topazian, M Farrell, J Syngal, S Lee, J Kamel, I Lennon, AM Knight, S Fujiwara, S Hruban, RH Canto, MI Goggins, M AF Kanda, Mitsuro Sadakari, Yoshihiko Borges, Michael Topazian, Mark Farrell, James Syngal, Sapna Lee, Jeffrey Kamel, Ihab Lennon, Anne Marie Knight, Spencer Fujiwara, Sho Hruban, Ralph H. Canto, Marcia Irene Goggins, Michael TI Mutant TP53 in Duodenal Samples of Pancreatic Juice From Patients With Pancreatic Cancer or High-Grade Dysplasia SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Tumor; Biomarker; Diagnostic; Early Detection ID HIGH-RISK INDIVIDUALS; INTRAEPITHELIAL NEOPLASIA; K-RAS; FAMILY-HISTORY; MUTATIONS; P53; DIAGNOSIS; PROGRESSION; CARCINOMA; LESIONS AB BACKGROUND & AIMS: Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer. METHODS: We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls. RESULTS: TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions. CONCLUSIONS: We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701. C1 [Kanda, Mitsuro; Sadakari, Yoshihiko; Borges, Michael; Knight, Spencer; Fujiwara, Sho; Hruban, Ralph H.; Goggins, Michael] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Kamel, Ihab] Johns Hopkins Med Inst, Dept Radiol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Lennon, Anne Marie] Johns Hopkins Med Inst, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Hruban, Ralph H.; Goggins, Michael] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA. [Topazian, Mark] Mayo Clin, Rochester, MI USA. [Farrell, James] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Jeffrey] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Syngal, Sapna] Univ Calif Los Angeles, Los Angeles, CA USA. RP Goggins, M (reprint author), Johns Hopkins Med Inst, Dept Pathol, 1550 Orleans St, Baltimore, MD 21231 USA. EM mgoggins@jhmi.edu RI Kanda, Mitsuro/M-4891-2014 FU National Institutes of Health [CA62924, R01CA120432, RC2CA148376]; Lustgarten Foundation for Pancreatic Cancer Research; Jimmy V Foundation; Michael Rolfe Foundation; Alan Graff Foundation; Karp Family H.H. Metals, Inc; Fund for Cancer Research; Susan Wojcicki and Dennis Troper; Michael Hooven and Susan Spies; Hugh and Rachel Victor FX Supported by National Institutes of Health grants (CA62924, R01CA120432, and RC2CA148376), the Lustgarten Foundation for Pancreatic Cancer Research, the Jimmy V Foundation, Susan Wojcicki and Dennis Troper, the Michael Rolfe Foundation, the Alan Graff Foundation, Karp Family H.H. Metals, Inc, Fund for Cancer Research, Michael Hooven and Susan Spies, and Hugh and Rachel Victor. Recombinant secretin was provided for this study by ChiRhoClin, Inc, and Repligen. NR 31 TC 35 Z9 35 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2013 VL 11 IS 6 BP 719 EP + DI 10.1016/j.cgh.2012.11.016 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 162ZZ UT WOS:000320306400024 PM 23200980 ER PT J AU Yeh, DD Velmahos, GC AF Yeh, D. D. Velmahos, G. C. TI Disease-specific nutrition therapy: one size does not fit all SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY LA English DT Review DE Nutrition; Immunonutrition; Renal failure; Hepatic failure; Obesity; Pulmonary failure ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; SEVERE ACUTE-PANCREATITIS; EARLY ENTERAL NUTRITION; GAMMA-LINOLENIC ACID; SYSTEMIC INFLAMMATORY RESPONSE; TOTAL PARENTERAL-NUTRITION; SHORT-BOWEL SYNDROME; MECHANICALLY VENTILATED PATIENTS; ACUTE LUNG INJURY AB The delivery of adequate nutrition is an integral part of the care of the critically ill surgical patient, and the provision of nutrition may have a greater impact on outcome than many other therapies commonly employed in the treatment of certain disease states. A review of the existing literature was performed to summarize the evidence for utilizing disease-specific nutrition in critically ill surgical patients. Enteral nutrition, unless specifically contraindicated, is always preferable to parenteral nutrition. Methodological heterogeneity and conflicting results plague research in immunonutrition, and routine use is not currently recommended in critically ill patients. There is currently insufficient evidence to recommend the routine initial use of most disease-specific formulas, as most patients with the disease in question will tolerate standard enteral formulas. However, the clinician should closely monitor for signs of intolerance and utilize disease-specific formulas when appropriate. C1 [Yeh, D. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA. [Velmahos, G. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Chief Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston 165 Cambridge St 810, Boston, MA 02114 USA. EM Dyeh2@partners.org NR 171 TC 1 Z9 1 U1 0 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-9933 J9 EUR J TRAUMA EMERG S JI Eur. J. Trauma Emerg. Surg. PD JUN PY 2013 VL 39 IS 3 BP 215 EP 233 DI 10.1007/s00068-013-0264-8 PG 19 WC Emergency Medicine SC Emergency Medicine GA 159MR UT WOS:000320050000003 PM 26815228 ER PT J AU Surman, CBH Hammerness, PG Pion, K Faraone, SV AF Surman, Craig B. H. Hammerness, Paul G. Pion, Katie Faraone, Stephen V. TI Do stimulants improve functioning in adults with ADHD? A review of the literature SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Attention deficit hyperactivity isorder; ADHD; Pharmacotherapy; Stimulant; Function; Quality of life ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SALTS EXTENDED-RELEASE; DOUBLE-BLIND; EFFICACY; QUALITY; LIFE; PREVALENCE; SAFETY; METHYLPHENIDATE AB ADHD is prevalent in adulthood and stimulant pharmacotherapy is the primary treatment for uncomplicated presentations. ADHD is associated with significant functional impairment in major life roles. Measurement of the efficacy of stimulant treatment for adult ADHD therefore should include assessment of improvement in role function. A literature search was conducted to identify studies that measured change in function with stimulant treatment in adult ADHD using measures other than global clinical impression or global assessment of function ratings. Five studies were identified that met our search criteria. Evidence of functional improvement with stimulant treatment was found with the following validated self-report measures of functional wellbeing employed across these studies: the Medical Outcome Study 36-item Short Form Health Survey; ADHD Impact Module for Adults; Quality of Life Enjoyment and Satisfaction scale-Short Form; Sheehan Disability Scale, and Social Adjustment Scale-Self-Report. We conclude that investigations using self-report scales provide evidence that stimulant treatment translates into measurable improvement in daily function for adults with ADHD. Further investigation could better characterize the mediators and moderators of individual improvement, an important step towards the personalization of treatment for ADHD in adulthood. (c) 2012 Elsevier B.V. and ECNP. All rights reserved. C1 [Surman, Craig B. H.; Hammerness, Paul G.; Pion, Katie] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Suite 2000,185 Alewife Brook Pkwy, Cambridge, MA 02138 USA. EM csurman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Abbott; Alza; Cephalon; Eli Lilly; Hilda and Preston Davis Foundation; McNeil; Merck; National Institutes of Health; New River; Nordic Naturals; Organon; Pfizer; Shire; Takeda; Ortho-McNeil Janssen; Elminda Ltd.; GlaxoSmithKline; Johnson Johnson; Novartis; Alcobra; National Institutes of Health (NIH); Humana/Springer; Guilford Press; Oxford University Press FX Dr. Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck, National Institutes of Health, New River, Nordic Naturals, Organon, Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil, Novartis, and Shire; and has been a consultant/advisor for McNeil, Shire, Somaxon 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, http://www.mghcme.org. Dr Surman receives royalties from books: "ADHD in Adults: A Practical Guide to Evaluation and Management" (Humana/Springer) and "FAST MINDS: How To Thrive If You Have ADHD (Or Think You Might)".; In the past 2 years, Dr. Hammerness has participated in CME activities/professional talks supported by the following pharmaceutical companies: Ortho-McNeil Janssen, Shire. Dr. Hammerness has 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 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, http://www.mghcme.org.; In the past year, Dr. Faraone received consulting income and research support from Shire and Alcobra and research support from 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. Dr. Faraone receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health and Genetics of Mental Disorders and from Oxford University Press: Schizophrenia: The Facts. NR 36 TC 17 Z9 18 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JUN PY 2013 VL 23 IS 6 BP 528 EP 533 DI 10.1016/j.euroneuro.2012.02.010 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 159US UT WOS:000320073400011 PM 23391411 ER PT J AU Reardon, DA Wucherpfennig, KW Freeman, G Wu, CJ Chiocca, EA Wen, PY Curry, WT Mitchell, DA Fecci, PE Sampson, JH Dranoff, G AF Reardon, David A. Wucherpfennig, Kai W. Freeman, Gordon Wu, Catherine J. Chiocca, E. Antonio Wen, Patrick Y. Curry, William T., Jr. Mitchell, Duane A. Fecci, Peter E. Sampson, John H. Dranoff, Glenn TI An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma SO EXPERT REVIEW OF VACCINES LA English DT Review DE dendritic cells; glioblastoma; immunosuppression; immunotherapy; vaccine ID GROWTH-FACTOR RECEPTOR; CENTRAL-NERVOUS-SYSTEM; REGULATORY T-CELLS; COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; ANTITUMOR IMMUNE-RESPONSES; RESISTANT PROSTATE-CANCER; PROGRESSION-FREE SURVIVAL; HIGH-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA AB Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancers, including GBM. Much historical dogma depicting the CNS as immunoprivileged has been replaced by data demonstrating CNS immunocompetence and active interaction with the peripheral immune system. Several glioma antigens have been identified for potential immunotherapeutic exploitation. Active immunotherapy studies for GBM, supported by preclinical data, have focused on tumor lysate and synthetic antigen vaccination strategies. Results to date confirm consistent safety, including a lack of autoimmune reactivity; however, modest efficacy and variable immunogenicity have been observed. These findings underscore the need to optimize vaccination variables and to address challenges posed by systemic and local immunosuppression inherent to GBM tumors. Additional immunotherapy strategies are also in development for GBM. Future studies may consider combinatorial immunotherapy strategies with complimentary actions. C1 [Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Wucherpfennig, Kai W.; Freeman, Gordon; Wu, Catherine J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wu, Catherine J.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA. [Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Curry, William T., Jr.; Fecci, Peter E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Mitchell, Duane A.; Sampson, John H.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Reardon, DA (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. EM david_reardon@dfci.harvard.edu FU Celldex Therapeutics FX JH Sampson has a consultancy, honoraria and research funding with Celldex Therapeutics. G Freeman has a consultancy with CoStim Pharmaceuticals and grants/patents/pending royalties with Bristol-Myers Squibb/Medarex, Roche/Genentech, Merck, EMD-Serono, Boehringer-Ingelheim, GlaxoSmithKline and CoStim Pharmaceuticals. DA Mitchell and JH Sampson have grants/patents/pending royalties through Celldex Therapeutics and Annias Immunotherapeutics. 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 241 TC 26 Z9 26 U1 0 U2 14 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 JUN PY 2013 VL 12 IS 6 BP 597 EP 615 DI 10.1586/ERV.13.41 PG 19 WC Immunology SC Immunology GA 161CO UT WOS:000320169300008 PM 23750791 ER PT J AU Fusco, DN Brisac, C John, SP Huang, YW Chin, CR Xie, T Zhao, H Jilg, N Zhang, LL Chevaliez, S Wambua, D Lin, WY Peng, L Chung, RT Brass, AL AF Fusco, Dahlene N. Brisac, Cynthia John, Sinu P. Huang, Yi-Wen Chin, Christopher R. Xie, Tiao Zhao, Hong Jilg, Nikolaus Zhang, Leiliang Chevaliez, Stephane Wambua, Daniel Lin, Wenyu Peng, Lee Chung, Raymond T. Brass, Abraham L. TI A Genetic Screen Identifies Interferon-alpha Effector Genes Required to Suppress Hepatitis C Virus Replication SO GASTROENTEROLOGY LA English DT Article DE Treatment; Gene Regulation; Virology; Mechanism ID RAT-LIVER; PATHWAYS; PROTEINS; CELLS; EXPRESSION; COFACTOR; GAMMA AB BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-alpha (IFN alpha) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFN alpha (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFN alpha. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach. METHODS: We performed an unbiased genome-wide small interfering RNA screen to identify IEGs that inhibit HCV. Huh7.5.1 hepatoma cells were transfected with small interfering RNAs incubated with IFN alpha and then infected with JFH1 HCV. Cells were stained using HCV core antibody, imaged, and analyzed to determine the percent infection. Candidate IEGs detected in the screen were validated and analyzed further. RESULTS: The screen identified 120 previously unreported IEGs. From these, we more fully evaluated the following: asparagine-linked glycosylation 10 homolog (yeast, alpha-1,2-glucosyltransferase); butyrylcholinesterase; dipeptidylpeptidase 4 (CD26, adenosine deaminase complexing protein 2); glucokinase (hexokinase 4) regulator; guanylate cyclase 1, soluble, beta 3; MYST histone acetyltransferase 1; protein phosphatase 3 (formerly 2B), catalytic subunit, beta isoform; peroxisomal proliferator-activated receptor-gamma-DBD-interacting protein 1; and solute carrier family 27 (fatty acid transporter), member 2; and demonstrated that they enabled IFN alpha-mediated suppression of HCV at multiple steps of its life cycle. Expression of these genes had more potent effects against flaviviridae because a subset was required for IFN alpha to suppress dengue virus but not influenza A virus. In addition, many of the host genes detected in this screen (92%) were not transcriptionally stimulated by IFN alpha; these genes represent a heretofore unknown class of non-IFN-stimulated gene IEGs. CONCLUSIONS: We performed a whole-genome loss-of-function screen to identify genes that mediate the effects of IFN alpha against human pathogenic viruses. We found that IFN alpha restricts HCV via actions of general and specific IEGs. C1 [Fusco, Dahlene N.; Brisac, Cynthia; Jilg, Nikolaus; Chevaliez, Stephane; Wambua, Daniel; Lin, Wenyu; Peng, Lee; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [John, Sinu P.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Huang, Yi-Wen] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan. [Huang, Yi-Wen] Cathay Gen Hosp, Med Ctr, Hosp Liver Ctr, Taipei, Taiwan. [Huang, Yi-Wen] Taipei Med Univ, Sch Med, Taipei, Taiwan. [Chin, Christopher R.; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01605 USA. [Xie, Tiao] Harvard Univ, Sch Med, Image & Data Anal Core, Boston, MA USA. [Zhao, Hong] Peking Univ, Hosp Beijing 1, Dept Infect Dis, Beijing, Peoples R China. [Zhang, Leiliang] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China. [Zhang, Leiliang] Peking Union Med Coll, Beijing 100021, Peoples R China. [Chevaliez, Stephane] Univ Paris Est, Dept Virol, Hosp Univ Henri Mondor, Creteil, France. [John, Sinu P.; Chin, Christopher R.; Brass, Abraham L.] Ragon Inst, Charlestown, MA USA. RP Brass, AL (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, 55 Lake Ave North, Worcester, MA 01605 USA. EM rtchung@partners.org; abraham.brass@umassmed.edu FU NIH [U19 AI082630, 1R01AI091786]; American Association for the Study of Liver Disease; ANRS (French National Agency for Research on AIDS and Viral Hepatitis); Gilead FX This work was supported by NIH U19 AI082630 (R. T. Chung, A. L. Brass, and D. N. Fusco). D. N. Fusco is grateful for support from a Clinical and Translational Research Award from the American Association for the Study of Liver Disease. S. Chevalier is grateful for support from ANRS (French National Agency for Research on AIDS and Viral Hepatitis) and Gilead. A. L. Brass is grateful to the Charles H. Hood Foundation, the Bill and Melinda Gates Foundation, the Phillip T. and Susan M. Ragon Foundation, the University of Massachusetts Medical School Center for AIDS Research, and the NIH (1R01AI091786) for their generous support. NR 30 TC 21 Z9 21 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2013 VL 144 IS 7 BP 1438 EP U210 DI 10.1053/j.gastro.2013.02.026 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 151ZI UT WOS:000319498500027 PM 23462180 ER PT J AU Gao, T Zhou, DW Yang, CH Singh, T Penzo-Mendez, A Maddipati, R Tzatsos, A Bardeesy, N Avruch, J Stanger, BZ AF Gao, Tao Zhou, Dawang Yang, Chenghua Singh, Tarjinder Penzo-Mendez, Alfredo Maddipati, Ravikanth Tzatsos, Alexandros Bardeesy, Nabeel Avruch, Joseph Stanger, Ben Z. TI BASIC AND TRANSLATIONAL-PANCREAS SO GASTROENTEROLOGY LA English DT Editorial Material DE Mouse Model; Signal Transduction; Hpo; Wts ID HIPPO SIGNALING PATHWAY; ORGAN SIZE CONTROL; YAP; KINASES; LIVER; MST1; PROLIFERATION; INACTIVATION; REGENERATION; MAMMALS AB BACKGROUND & AIMS: The Hippo signaling pathway is a context-dependent regulator of cell proliferation, differentiation, and apoptosis in species ranging from Drosophila to humans. In this study, we investigated the role of the core Hippo kinases-Mst1 and Mst2-in pancreatic development and homeostasis. METHODS: We used a Cre/LoxP system to create mice with pancreas-specific disruptions in Mst1 and Mst2 (Pdx1-Cre; Mst1(-/-); Mst2(fl/fl) mice), the mammalian orthologs of Drosophila Hippo. We used a transgenic approach to overexpress Yap, the downstream mediator of Hippo signaling, in the developing pancreas of mice. RESULTS: Contrary to expectations, the pancreatic mass of Pdx1-Cre; Mst1(-/-); Mst2(fl/fl) mice was reduced compared with wild-type mice, largely because of postnatal de-differentiation of acinar cells into duct-like cells. Development of this phenotype coincided with postnatal reactivation of YAP expression. Ectopic expression of YAP during the secondary transition (a stage at which YAP is normally absent) blocked differentiation of the endocrine and exocrine compartments, whereas loss of a single Yap allele reduced acinar de-differentiation. The phenotype of Pdx1-Cre; Mst1(-/-); Mst2(fl/fl) mice recapitulated cellular and molecular changes observed during chemicalinduced pancreatitis in mice. CONCLUSIONS: The mammalian Hippo kinases, and YAP, maintain postnatal pancreatic acinar differentiation in mice. C1 [Gao, Tao; Yang, Chenghua; Singh, Tarjinder; Penzo-Mendez, Alfredo; Maddipati, Ravikanth; Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Gao, Tao; Yang, Chenghua; Penzo-Mendez, Alfredo; Maddipati, Ravikanth; Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Zhou, Dawang; Tzatsos, Alexandros; Bardeesy, Nabeel; Avruch, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zhou, Dawang] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen, Fujian, Peoples R China. RP Stanger, BZ (reprint author), Univ Penn, Perelman Sch Med, 421 Curie Blvd, Philadelphia, PA 19104 USA. EM bstanger@exchange.upenn.edu FU NCI NIH HHS [K99 CA158582, P30 CA016520, R01 CA133557, R01 CA136567]; NIDDK NIH HHS [P30 DK043351, DK083111, DP2 DK083111, P30 DK040561, P30 DK050306, P30-DK050306, R01 DK083355, T32 DK007066]; PHS HHS [GSE35004] NR 23 TC 37 Z9 37 U1 1 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2013 VL 144 IS 7 BP 1543 EP U380 DI 10.1053/j.gastro.2013.02.037 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 151ZI UT WOS:000319498500037 PM 23454691 ER PT J AU Press, MJ Scanlon, DP Ryan, AM Zhu, JS Navathe, AS Mittler, JN Volpp, KG AF Press, Matthew J. Scanlon, Dennis P. Ryan, Andrew M. Zhu, Jingsan Navathe, Amol S. Mittler, Jessica N. Volpp, Kevin G. TI Limits Of Readmission Rates In Measuring Hospital Quality Suggest The Need For Added Metrics SO HEALTH AFFAIRS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; MORTALITY-RATES; HEALTH-CARE; PERFORMANCE-MEASURES; TEACHING STATUS; TRIAL AB Recent national policies use risk-standardized readmission rates to measure hospital performance on the theory that readmissions reflect dimensions of the quality of patient care that are influenced by hospitals. In this article our objective was to assess readmission rates as a hospital quality measure. First we compared quartile rankings of hospitals based on readmission rates in 2009 and 2011 to see whether hospitals maintained their relative performance or whether shifts occurred that suggested either changes in quality or random variation. Next we examined the relationship between readmission rates and several commonly used hospital quality indicators, including risk-standardized mortality rates, volume, teaching status, and process-measure performance. We found that quartile rankings fluctuated and that readmission rates for lower-performing hospitals in 2009 tended to improve by 2011, while readmission rates for higher-performing hospitals tended to worsen. Regression to the mean (a form of statistical noise) accounted for a portion of the changes in hospital performance. We also found that readmission rates were higher in teaching hospitals and were weakly correlated with the other indicators of hospital quality. Policy makers should consider augmenting the use of readmission rates with other measures of hospital performance during care transitions and should build on current efforts that take a communitywide approach to the readmissions issue. C1 [Press, Matthew J.] Weill Cornell Med Coll, New York, NY USA. [Scanlon, Dennis P.] Penn State Univ, Hlth Policy & Adm, Coll Hlth & Human Dev, State Coll, PA USA. [Ryan, Andrew M.] Weill Cornell Med Coll, Div Outcomes & Effectiveness Res, New York, NY USA. [Zhu, Jingsan] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Navathe, Amol S.] Harvard Univ, Sch Med, Boston, MA USA. [Navathe, Amol S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Navathe, Amol S.] Harvard Vanguard Med Associates, Boston, MA USA. [Mittler, Jessica N.] Penn State Univ, Dept Hlth Policy Adm, State Coll, PA USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Center, Philadelphia, PA USA. RP Press, MJ (reprint author), Weill Cornell Med Coll, New York, NY USA. EM map9069@med.cornell.edu FU Commonwealth Fund; Department of Veterans Affairs Health Services Research and Development (VA HSRD); Agency for Healthcare Research and Quality [K01HS018546-01] FX Some results from this study were presented at the Society of General Internal Medicine Annual Meeting, Orlando, Florida, May 2012. This project was funded by the Commonwealth Fund (principal investigator: Dennis Scanlon). The authors thank the Department of Veterans Affairs Health Services Research and Development (VA HSR&D) for the support of Kevin Volpp. Matthew Press is supported in part by funds provided to him as a Nanette Laitman Clinical Scholar in Public Health at Weill Cornell Medical College. Andrew Ryan is supported by Grant No. K01HS018546-01 from the Agency for Healthcare Research and Quality. The authors also thank Andrea Troxel of the University of Pennsylvania for statistical advice. NR 36 TC 23 Z9 23 U1 4 U2 13 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 JUN PY 2013 VL 32 IS 6 BP 1083 EP 1091 DI 10.1377/hlthaff.2012.0518 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 163XV UT WOS:000320372800010 PM 23733983 ER PT J AU Olfson, M Marcus, SC AF Olfson, Mark Marcus, Steven C. TI Decline In Placebo-Controlled Trial Results Suggests New Directions For Comparative Effectiveness Research SO HEALTH AFFAIRS LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; ACUTE MYOCARDIAL-INFARCTION; RESEARCH-AND-DEVELOPMENT; ACTIVE-CONTROL TRIALS; BIOMEDICAL-RESEARCH; OUTCOMES; DESIGN; TRENDS; ISSUES; SIZE AB The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy. C1 [Olfson, Mark] Columbia Univ, New York, NY 10027 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equity 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 Olfson, M (reprint author), Columbia Univ, New York, NY 10027 USA. EM mo49@columbia.edu FU Agency for Healthcare Research and Quality [U19 HS021112]; New York State Psychiatric Institute FX Mark Olfson's work on this project was supported by the Agency for Healthcare Research and Quality (Grant No. U19 HS021112) and the New York State Psychiatric Institute. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. No human subjects were involved in the conduct of this study. Steven Marcus had access to all of the extracted data in the study and takes responsibility for the accuracy of the data analysis. A bibliography of the 315 articles selected for review is available from Olfson on request. NR 48 TC 7 Z9 7 U1 1 U2 5 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUN PY 2013 VL 32 IS 6 BP 1116 EP 1125 DI 10.1377/hlthaff.2012.1353 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 163XV UT WOS:000320372800014 PM 23733987 ER PT J AU Morrison, P Nikolajski, C Zickmund, S AF Morrison, Penelope Nikolajski, Cara Zickmund, Susan TI 'When we think about risk, we think about rights': community-based organisations' staff members' perspectives on risk, resiliency and rights in Juiz de Fora, Brazil SO HEALTH RISK & SOCIETY LA English DT Article DE public health; risk; risk perception; young people; Brazil ID SAO-PAULO; PROTECTIVE FACTORS; SEXUAL-BEHAVIOR; DRUG-USE; HEALTH; ADOLESCENTS; YOUTH; CHILDREN; CONFLICT; STUDENTS AB In this article, we draw on a qualitative case study undertaken in 2008 and 2009 of staff working at community-based organisations for at-risk youth in Juiz de Fora, Brazil, to examine staff members' perspectives of adolescent health-risk behaviours and resiliency. We use these data to explore how recent policy changes in Brazil have led to a shift in the ways in which adolescent risk taking is perceived by those working in youth services, and to suggest the influence that this has had on the way in which these entities promote resiliency among the population they serve. Specifically, we argue that Brazil's Child and Adolescent Act of 1990, a policy derived from the United Nations Convention on the Rights of the Child, has been instrumental in reframing for the community-based organisations the question of adolescent health-risk behaviours into a rights-based framework and has shifted the perceptions of those working at such organisations as to who a youth at-risk' is, why young people engage in risk taking and how best to promote resiliency. This work has implications for understanding both how risk and resiliency are constructed in different social and cultural contexts and how such concepts may change over time due to shifting socio-political climates. C1 [Morrison, Penelope] Univ Pittsburgh, RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA 15260 USA. [Nikolajski, Cara] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Zickmund, Susan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Morrison, P (reprint author), Univ Pittsburgh, RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA 15260 USA. EM morrisonpk@upmc.edu NR 62 TC 0 Z9 0 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1369-8575 J9 HEALTH RISK SOC JI Health Risk Soc. PD JUN 1 PY 2013 VL 15 IS 4 BP 347 EP 362 DI 10.1080/13698575.2013.796347 PG 16 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 160DV UT WOS:000320098100004 ER PT J AU Pretorius, E Lipinski, B AF Pretorius, E. Lipinski, B. TI Differences in Morphology of Fibrin Clots Induced with Thrombin and Ferric Ions and Its Pathophysiological Consequences SO HEART LUNG AND CIRCULATION LA English DT Article DE Scanning electron microscopy; Fibrin; Ferric iron AB The activation of blood coagulation leads to the formation of thrombin that, in turn, converts soluble plasma fibrinogen into insoluble fibrin clot. In healthy individuals, fibrin is effectively degraded; however, in prothrombotic states, proteolysis of fibrin clots are often delayed or even inhibited, and is associated with altered fibrin structure. We have previously shown that in inflammatory conditions like stroke and diabetes, this fibrin forms dense matted deposits. Although there are several factors that modify fibrin structure and delay fibrinolysis in these conditions, no mechanism is yet known to be responsible for a persistent presence of thrombi in the coronary and/or cerebral circulations. It seems, therefore, desirable to better understand this phenomenon in order to improve the effectiveness of thrombolytic therapies. Here, we show that ferric ions can activate non-enzymatic blood coagulation resulting in the formation of fibrin-like dense matted deposits (DMD) demonstrable by electron scanning microscopy (SEM). These DMDs are similar to those found in stroke and diabetes. On the basis of these findings we can conclude that the spontaneous formation of fibrin-like dense deposits in patients' blood may be a consequence of what is known as iron overload. Therefore, it is possible that inactivation of unbound iron in blood by small molecular weight chelating agents may prevent thrombotic consequences of the excessive accumulation of iron in the circulation. (c) 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. C1 [Pretorius, E.] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa. [Lipinski, B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa. EM resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384 NR 9 TC 9 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1443-9506 J9 HEART LUNG CIRC JI Heart Lung Circ. PD JUN PY 2013 VL 22 IS 6 BP 447 EP 449 DI 10.1016/j.hlc.2012.10.010 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 162WA UT WOS:000320295500008 PM 23219312 ER PT J AU Souter, I Smith, KW Williams, PL Ehrlich, S Hauser, R AF Souter, I. Smith, K. W. Williams, P. L. Ehrlich, S. Hauser, R. TI Association of urinary phthalate (UrP) metabolite concentrations with ovarian response and early in-vitro fertilization (IVF) outcomes SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 29th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUL 07-10, 2013 CL London, ENGLAND SP European Soc Human Reprod & Embryol (ESHRE) C1 [Souter, I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Smith, K. W.; Williams, P. L.; Ehrlich, S.; Hauser, R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2013 VL 28 SU 1 BP 36 EP 37 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 165FD UT WOS:000320467700080 ER PT J AU Anderson, RA McLaughlin, M Woods, DC Tilly, JL Telfer, EE AF Anderson, R. A. McLaughlin, M. Woods, D. C. Tilly, J. L. Telfer, E. E. TI Evaluation of oogonial stem cells and neo-oogenesis in ovaries of girls and women with Turner Syndrome: a pilot study SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 29th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUL 07-10, 2013 CL London, ENGLAND SP European Soc Human Reprod & Embryol (ESHRE) C1 [Anderson, R. A.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland. [McLaughlin, M.; Telfer, E. E.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland. [Woods, D. C.; Tilly, J. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Woods, D. C.; Tilly, J. L.] Harvard Univ, Sch Med, Dept OB GYN & Reprod Biol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2013 VL 28 SU 1 BP 52 EP 52 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 165FD UT WOS:000320467700115 ER PT J AU Sawicki, DE Machado, MA AF Sawicki, Darlene E. Machado, Monique A. TI NANDA-I With NIC NOC'n on Heaven's Door SO INTERNATIONAL JOURNAL OF NURSING KNOWLEDGE LA English DT Article DE NANDA-I; NNN; nursing language C1 [Machado, Monique A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Machado, MA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM m.a.machado81@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-3087 J9 INT J NURS KNOWL JI Int. J. Nurs. Knowl. PD JUN PY 2013 VL 24 IS 2 BP 64 EP 65 DI 10.1111/j.2047-3095.2013.01238.x PG 2 WC Nursing SC Nursing GA 161LU UT WOS:000320195300002 PM 23556468 ER PT J AU Barbesino, G Tomer, Y AF Barbesino, Giuseppe Tomer, Yaron TI Clinical Utility of TSH Receptor Antibodies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID THYROID-STIMULATING-ANTIBODY; AMIODARONE-INDUCED THYROTOXICOSIS; GRAVES-DISEASE; THYROTROPIN RECEPTOR; NEONATAL HYPERTHYROIDISM; BLOCKING AUTOANTIBODIES; PAINLESS THYROIDITIS; RADIOIODINE THERAPY; POLYETHYLENE-GLYCOL; SILENT THYROIDITIS AB Context: TSH receptor antibodies (TRAb) cause Graves' disease (GD) hyperthyroidism. Widely available TRAb measurement methods have been significantly improved recently. However, the role of TRAb measurement in the differential diagnosis of hyperthyroidism, the prediction of remission of GD hyperthyroidism, the prediction of fetal/neonatal thyrotoxicosis, and the clinical assessment of Graves' ophthalmopathy (GO) are controversial. Evidence Acquisition: We reviewed and analyzed the literature reporting primary data on the clinical use of TRAb. We focused our analyses on clinical studies analyzing third-generation TRAb assays. Evidence Synthesis: The performance of TRAb in the differential diagnosis of overt hyperthyroidism is excellent, with sensitivity and specificity in the upper 90%. TRAb can accurately predict short-term relapses of hyperthyroidism after a course of antithyroid drugs but are less effective in predicting long-term relapses or remissions. Pregnancies in women with GD with negative TRAb are highly unlikely to result in fetal hyperthyroidism, whereas high titers of TRAb in pregnancy require careful fetal monitoring. GD patients with GO frequently have high TRAb levels. However, there are insufficient data to use the test to predict the clinical course of GO and response to treatment. Conclusions: Third-generation TRAb assays are suitable in the differential diagnosis of hyperthyroidism. In GD, TRAbshould be tested before deciding whether methimazole can be stopped. TRAb should be used in pregnant women with GD to assess the risk of fetal thyrotoxicosis. The use of TRAb in GO requires further studies. C1 [Barbesino, Giuseppe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Endocrinol,Thyroid Unit, Boston, MA 02114 USA. [Tomer, Yaron] Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Barbesino, G (reprint author), Massachusetts Gen Hosp, Thyroid Unit, Div Endocrinol, Boston, MA 02114 USA. EM gbarbesino@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases [DK061659, DK067555, DK073681] FX This work was supported by Grants DK061659, DK067555, and DK073681 from National Institute of Diabetes and Digestive and Kidney Diseases ( to Y.T.). NR 86 TC 38 Z9 39 U1 3 U2 16 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 JUN PY 2013 VL 98 IS 6 BP 2247 EP 2255 DI 10.1210/jc.2012-4309 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155GS UT WOS:000319736500026 PM 23539719 ER PT J AU Rhee, CM Curhan, GC Alexander, EK Bhan, I Brunelli, SM AF Rhee, Connie M. Curhan, Gary C. Alexander, Erik K. Bhan, Ishir Brunelli, Steven M. TI Subclinical Hypothyroidism and Survival: The Effects of Heart Failure and Race SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ALL-CAUSE MORTALITY; MILD THYROID-DYSFUNCTION; RISK-FACTORS; CARDIOVASCULAR-DISEASE; COGNITIVE FUNCTION; REFERENCE LIMITS; NATIONAL-HEALTH; SERUM TSH; AGE; ADULTS AB Context: Studies examining the association between subclinical hypothyroidism and mortality have yielded conflicting results. Emerging data suggest these associations may depend upon underlying congestive heart failure (CHF) and/or race, but this has not been empirically determined. Objective: Our objective was to examine the association between subclinical hypothyroidism and hypothyroidism overall with mortality according to pre-existing CHF and race. Design and Participants: We examined the associations of subclinical hypothyroidism (TSH higher than assay upper limit of normal; total T-4 within reference) and hypothyroidism overall (TSH higher than assay upper limit of normal; total T-4 below lower limit of normal or within reference) with all-cause mortality among Third National Health and Nutrition Examination Survey participants stratified by CHF and race using multivariable Cox models. To confirm whether differences between strata were statistically significant, we tested for interaction on the basis of CHF (separately) and race by likelihood ratio testing. Results: There were 14 130 (95.0%) euthyroid controls and 749 (5.0%) participants with hypothyroidism, 691 (4.6%) of whom had subclinical disease. Subclinical hypothyroidism vs euthyroidism was associated with greater mortality in those with CHF but not in those without: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) = 1.44 (1.01-2.06) and 0.97 (0.85-1.11), respectively (P interaction = .03). Similar findings were observed for hypothyroidism overall. Hypothyroidism overall vs euthyroidism was associated with greater mortality in Black participants (HR = 1.44 [95% CI = 1.03-2.03]) but not in non-Blacks (HR = 0.95 [95% CI = 0.83-1.08]) (P interaction = .03). Conclusion: Among participants with CHF, subclinical hypothyroidism and hypothyroidism overall are associated with greater death risk. Additional studies are needed to confirm findings and explore possible mechanisms for the differential hypothyroidism-mortality association across race. C1 [Rhee, Connie M.; Curhan, Gary C.; Brunelli, Steven M.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA. [Curhan, Gary C.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Alexander, Erik K.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. [Brunelli, Steven M.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. [Rhee, Connie M.; Curhan, Gary C.; Alexander, Erik K.; Bhan, Ishir; Brunelli, Steven M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Curhan, Gary C.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02114 USA. [Brunelli, Steven M.] DaVita Clin Res, Minneapolis, MN 55404 USA. RP Rhee, CM (reprint author), Brigham & Womens Hosp, 75 Francis St,MRB-4, Boston, MA 02115 USA. EM crhee@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [DK093201, DK079056, DK91417]; Veracyte, Inc; Asuragen, Inc; Genzyme, Inc. FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health: DK093201 (to C.M.R.) and DK079056 (to S.M.B.), and DK91417 (to G.C.C.).; Disclosure Summary: C.M.R., G.C.C., and I.B. have nothing to declare. E.K.A. receives research support from Veracyte, Inc; Asuragen, Inc; and Genzyme, Inc. Since completing work on this study, S.M.B. has become a full-time employee at DaVita Clinical Research. NR 44 TC 20 Z9 21 U1 0 U2 1 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 JUN PY 2013 VL 98 IS 6 BP 2326 EP 2336 DI 10.1210/jc.2013-1039 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155GS UT WOS:000319736500037 PM 23720788 ER PT J AU Garcia, JM Swerdloff, R Wang, C Kyle, M Kipnes, M Biller, BMK Cook, D Yuen, KCJ Bonert, V Dobs, A Molitch, ME Merriam, GR AF Garcia, J. M. Swerdloff, R. Wang, C. Kyle, M. Kipnes, M. Biller, B. M. K. Cook, D. Yuen, K. C. J. Bonert, V. Dobs, A. Molitch, M. E. Merriam, G. R. TI Macimorelin (AEZS-130)-Stimulated Growth Hormone (GH) Test: Validation of a Novel Oral Stimulation Test for the Diagnosis of Adult GH Deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-COMPOSITION; GHRELIN-STIMULATION; ENDOCRINE-SOCIETY; DOUBLE-BLIND; SECRETAGOGUE; MEN; REPLACEMENT; SECRETION; SAFETY; MASS AB Context: In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion. Objective: The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD. Design: This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29) NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone. Main Outcome Measure: Peak GH area under the receiver operating characteristic curve after macimorelin was measured. Results: Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 +/- 5.69 and 17.71 +/- 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with82% sensitivity, 92% specificity, and13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported. Conclusion: Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test. C1 [Garcia, J. M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Swerdloff, R.; Wang, C.] Harbor UCLA Med Ctr, Torrance, CA 90502 USA. [Swerdloff, R.; Wang, C.] Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Kyle, M.] Radiant Res Inc, Chicago, IL 60654 USA. [Kipnes, M.] DGD Clin, San Antonio, TX 78229 USA. [Biller, B. M. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. [Cook, D.; Yuen, K. C. J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Bonert, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Dobs, A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Molitch, M. E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Merriam, G. R.] Univ Washington, Vet Affairs Puget Sound HCS, Seattle, WA 98108 USA. [Merriam, G. R.] Univ Washington, Vet Affairs Puget Sound HCS, Tacoma, WA 98108 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Ardana Biosciences Ltd and later; AEterna Zentaris Inc; facilities and services of the Michael E. DeBakey Veterans Affairs Medical Center and the Veterans Affairs Puget Sound Health Care System; Ardana Biosciences and/or terna Zentaris Inc.; Helsinn Therapeutics, Inc.; consulted for Novo Nordisk and Pfizer; Eli Lilly; Genentech; Pfizer; consulted for Novo Nordisk and Teva; Ipsen; Eli Lilly Co; Novo Nordisk; Novartis; Corcept and has consulted for Novo Nordisk; Corcept FX This work was supported by Ardana Biosciences Ltd and later by AEterna Zentaris Inc and by the facilities and services of the Michael E. DeBakey Veterans Affairs Medical Center and the Veterans Affairs Puget Sound Health Care System. All investigators received research support from Ardana Biosciences and/or terna Zentaris Inc.; J.M.G. is a consultant for AEterna Zentaris Inc and Helsinn Therapeutics Inc and receives research support from Helsinn Therapeutics, Inc. B.M.K.B. has served as a consultant to terna Zentaris Inc and received research support from and consulted for Novo Nordisk and Pfizer. K.C.J.Y. has received research support from and consulted for Novo Nordisk and Pfizer. G.R.M. has received research support from Eli Lilly, Genentech, and Pfizer and consulted for Novo Nordisk and Teva. M. E. M. received research support from Ipsen, Eli Lilly & Co, Novo Nordisk, Novartis, and Corcept and has consulted for Novo Nordisk, Corcept, and Novartis. The other authors have nothing to declare. NR 27 TC 11 Z9 11 U1 1 U2 6 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 JUN PY 2013 VL 98 IS 6 BP 2422 EP 2429 DI 10.1210/jc.2013-1157 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155GS UT WOS:000319736500049 PM 23559086 ER PT J AU Yuen, KCJ Conway, GS Popovic, V Merriam, GR Bailey, T Hamrahian, AH Biller, BMK Kipnes, M Moore, JA Humphriss, E Bright, GM Cleland, JL AF Yuen, Kevin C. J. Conway, Gerard S. Popovic, Vera Merriam, George R. Bailey, Timothy Hamrahian, Amir H. Biller, Beverly M. K. Kipnes, Mark Moore, Jerome A. Humphriss, Eric Bright, George M. Cleland, Jeffrey L. TI A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317): Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Growth Hormone-Deficient Adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PREPARATION NUTROPIN DEPOT; GH DEFICIENCY; REPLACEMENT THERAPY; PHARMACODYNAMIC CHARACTERISTICS; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; ENDOCRINE-SOCIETY; BODY-COMPOSITION; VISCERAL FAT; HALF-LIFE AB Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3-5.0 mu g/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between -1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing. C1 [Yuen, Kevin C. J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Conway, Gerard S.] Univ Coll London Hosp, London NW1 2BU, England. [Popovic, Vera] Univ Belgrade, Fac Med, Belgrade 11000, Serbia. Clin Ctr Serbia, Dept Neuroendocrinol, Belgrade 11000, Serbia. [Merriam, George R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst & Metab Endocrinol, Seattle, WA 98493 USA. [Merriam, George R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst & Metab Endocrinol, Tacoma, WA 98493 USA. [Bailey, Timothy] AMCR Inst, Escondido, CA 92026 USA. [Hamrahian, Amir H.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Kipnes, Mark] Endocrinol Diabet & Glandular Dis Clin, San Antonio, TX 78229 USA. [Moore, Jerome A.] Pacific Biodev LLC, Emeryville, CA 94608 USA. [Humphriss, Eric; Bright, George M.; Cleland, Jeffrey L.] Versartis Inc, Redwood City, CA 94065 USA. RP Bright, GM (reprint author), Versartis Inc, 275 Shoreline Dr,Suite 450, Redwood City, CA 94065 USA. EM gbright@versartis.com FU Versartis, Inc.; National Center for Advancing Translational Sciences at the National Institutes of Health [UL1RR024140]; Harvard Clinical and Translational Science Center from the National Center for Research Resources [1 UL1 RR025758-04] FX This work was supported by Versartis, Inc., the National Center for Advancing Translational Sciences at the National Institutes of Health (grant UL1RR024140 to K.C.J.Y.) and the Harvard Clinical and Translational Science Center from the National Center for Research Resources (grant 1 UL1 RR025758-04 to B.M.K.B.). NR 38 TC 17 Z9 19 U1 0 U2 15 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 JUN PY 2013 VL 98 IS 6 BP 2595 EP 2603 DI 10.1210/jc.2013-1437 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155GS UT WOS:000319736500069 PM 23585663 ER PT J AU Prudente, S Morini, E Marselli, L Baratta, R Copetti, M Mendonca, C Andreozzi, F Chandalia, M Pellegrini, F Bailetti, D Alberico, F Shah, H Abate, N Sesti, G Frittitta, L Marchetti, P Doria, A Trischitta, V AF Prudente, Sabrina Morini, Eleonora Marselli, Lorella Baratta, Roberto Copetti, Massimiliano Mendonca, Christine Andreozzi, Francesco Chandalia, Manisha Pellegrini, Fabio Bailetti, Diego Alberico, Federica Shah, Hetal Abate, Nicola Sesti, Giorgio Frittitta, Lucia Marchetti, Piero Doria, Alessandro Trischitta, Vincenzo TI Joint Effect of Insulin Signaling Genes on Insulin Secretion and Glucose Homeostasis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; CARDIOVASCULAR RISK; RESISTANCE; POLYMORPHISM; RECEPTOR; VARIANT; ISLETS; TISSUE; ONSET AB Context: Reduced insulin signaling in insulin secreting beta-cells causes defective insulin secretion and hyperglycemia in mice. Objective: We investigated whether functional polymorphisms affecting insulin signaling (ie, ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; and TRIB3 Q84R, rs2295490) exert a joint effect on insulin secretion and abnormal glucose homeostasis (AGH). Design: Insulin secretion was evaluated by 1) the disposition index (DI) from an oral glucose tolerance test (OGTT) in 829 individuals; 2) insulin secretion stimulation index (SI) in islets from nondiabetic donors after glucose (n = 92) or glibenclamide (n = 89) stimulation. AGH (including impaired fasting glucose and/or impaired glucose tolerance or type 2 diabetes; T2D) was evaluated in case-control studies from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) Consortium (n = 6607). Results: Genotype risk score, obtained by totaling individual weighted risk allele effects, was associated with the following: 1) DI (P = .005); 2) glucose and glibenclamide SI (P = .46 and P = .009); or 3) AGH(odds ratio 1.08, 95% confidence interval 1.03-1.13; P = .001). We observed an inverse relationship between genetic effect and age at AGH onset, as indicated by a linear correlation between AGH-genotype risk score odds ratios and age-at-diagnosis cutoffs (R-2 = 0.80, P < .001). Conclusions: Functional polymorphisms affecting insulin signaling exert a joint effect on both in vivo and in vitro insulin secretion as well as on early-onset AGH. Our data provide further evidence that abnormal insulin signaling reduces beta-cell function and impairs glucose homeostasis. C1 [Prudente, Sabrina; Bailetti, Diego; Alberico, Federica; Trischitta, Vincenzo] Ist Ricovero Cura Carattere Sci, Casa Sollievo Sofferenza Mendel Lab, I-71013 San Giovanni Rotondo, Italy. [Copetti, Massimiliano; Pellegrini, Fabio] Ist Ricovero Cura Carattere Sci, Unit Biostat, I-71013 San Giovanni Rotondo, Italy. [Trischitta, Vincenzo] Ist Ricovero Cura Carattere Sci, Res Unit Diabet & Endocrine Dis, I-71013 San Giovanni Rotondo, Italy. [Morini, Eleonora; Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy. [Marselli, Lorella; Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy. [Baratta, Roberto; Frittitta, Lucia] Univ Catania, Dept Mol & Clin Biomed, I-95125 Catania, Italy. [Mendonca, Christine; Shah, Hetal; Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA. [Andreozzi, Francesco; Sesti, Giorgio] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Copetti, Massimiliano; Abate, Nicola] Univ Texas SW Med Ctr Dallas, Dept Med, Div Endocrinol & Metab, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA. [Pellegrini, Fabio] Consorzio Mario Negri Sud, Unit Biostat, Chieti, Italy. [Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Doria, Alessandro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Prudente, S (reprint author), CSS Mendel Inst, Viale Regina Margherita 261, I-00198 Rome, Italy. EM s.prudente@css-mendel.it; vincenzo.trischitta@uniroma1.it RI Sesti, Giorgio/B-1509-2012; Marchetti, Piero/J-7439-2013; Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016; Copetti, Massimiliano/K-3186-2016; OI Marchetti, Piero/0000-0003-4907-0635; Prudente, Sabrina/0000-0001-9220-8981; Sesti, Giorgio/0000-0002-1618-7688; Trischitta, Vincenzo/0000-0003-1174-127X; Copetti, Massimiliano/0000-0002-7960-5947; Andreozzi, Francesco/0000-0001-9375-1513 FU Italian Ministry of Health; European Union [LSHM-CT-2004-512013]; University of Rome "Sapienza" FX This work was partly supported by the Italian Ministry of Health (Ricerca Corrente 2011 and 2012, to S.P., F.P., and V.T) and by the European Union (FP6 EUGENE2 Grant LSHM-CT-2004-512013, to G.S.). The source of funding for our manuscript is the University of Rome "Sapienza". NR 24 TC 8 Z9 8 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2013 VL 98 IS 6 BP E1143 EP E1147 DI 10.1210/jc.2012-4282 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155GS UT WOS:000319736500016 PM 23633196 ER PT J AU Serra, V Eichhorn, PJA Garcia-Garcia, C Ibrahim, YH Prudkin, L Sanchez, G Rodriguez, O Anton, P Parra, JL Marlow, S Scaltriti, M Perez-Garcia, J Prat, A Arribas, J Hahn, WC Kim, SY Baselga, J AF Serra, Violeta Eichhorn, Pieter J. A. Garcia-Garcia, Celina Ibrahim, Yasir H. Prudkin, Ludmila Sanchez, Gertrudis Rodriguez, Olga Anton, Pilar Parra, Josep-Lluis Marlow, Sara Scaltriti, Maurizio Perez-Garcia, Jose Prat, Aleix Arribas, Joaquin Hahn, William C. Kim, So Young Baselga, Jose TI RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RIBOSOMAL S6 KINASE; CAP-DEPENDENT TRANSLATION; DUAL PI3K/MTOR INHIBITOR; VIVO ANTITUMOR-ACTIVITY; PROTEIN-KINASE; FUNCTIONAL-CHARACTERIZATION; CELL-PROLIFERATION; INDUCED SENESCENCE; RNAI SCREEN; PHASE-I AB The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases RPS6KA2 (RSK3) and RPS6KA6 (RSK4). We demonstrate that overexpression of RSK3 or RSK4 supports proliferation upon PI3K inhibition both in vitro and in vivo, in part through the attenuation of the apoptotic response and upregulation of protein translation. Notably, the addition of MEK- or RSK-specific inhibitors can overcome these resistance phenotypes, both in breast cancer cell lines and patient-derived xenograft models with elevated levels of RSK activity. These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK. C1 [Serra, Violeta; Garcia-Garcia, Celina; Ibrahim, Yasir H.; Rodriguez, Olga; Anton, Pilar; Baselga, Jose] Vall dHebron Inst Oncol, Barcelona, Spain. [Eichhorn, Pieter J. A.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Prudkin, Ludmila; Sanchez, Gertrudis] Vall dHebron Inst Oncol, Mol Pathol Grp, Barcelona, Spain. [Parra, Josep-Lluis; Arribas, Joaquin] Vall dHebron Inst Oncol, Growth Factors Grp, Barcelona, Spain. [Marlow, Sara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Scaltriti, Maurizio; Baselga, Jose] Human Oncol & Pathogenesis Program, New York, NY USA. [Scaltriti, Maurizio; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Perez-Garcia, Jose] Vall dHebron Inst Oncol, Breast Canc & Melanoma Grp, Barcelona, Spain. [Prat, Aleix] Vall dHebron Inst Oncol, Translat Genom Unit, Barcelona, Spain. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Kim, So Young] Duke Univ, Med Ctr, Duke RNAi Screening Facil, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. RP Kim, SY (reprint author), Duke Univ, Med Ctr, Box 3053, Durham, NC 27710 USA. EM soyoung.kim@duke.edu; baselgaj@mskcc.org RI Arribas, Joaquin/M-4482-2014; Prat, Aleix/P-8561-2014 OI Arribas, Joaquin/0000-0002-0504-0664; Prat, Aleix/0000-0003-2377-540X FU Breast Cancer Research Foundation; European Research Council [AdG09250244]; Instituto de Salud Carlos III [Intrasalud PSO9/00623]; Novartis; FERO foundation; DFCI-Novartis Drug Discovery Program [R01 CA130988, RC2 CA148268, U54CA112962]; Snyder Medical Research Foundation FX The authors thank Anna Schinzel of the DFCI RNAi facility for assistance with reagents and Sadhna Vora and Jeff Engelman for helpful discussion. The authors also thank Emmanuelle Di Tomaso and Michel Maira (Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA, and Basel, Switzerland) for the supply of BEZ235 and BKM120. S.Y. Kim thanks Joseph Nevins for advice and generous support. This research was supported by the Breast Cancer Research Foundation (to J. Baselga), the European Research Council (AdG09250244 to J. Baselga), the Instituto de Salud Carlos III (Intrasalud PSO9/00623 to J. Baselga), a noncommercial research agreement with Novartis (to J. Baselga), FERO foundation supporting research grants (to J. Baselga), the DFCI-Novartis Drug Discovery Program (to W.C. Hahn), R01 CA130988 (to W.C. Hahn), RC2 CA148268 (to W.C. Hahn), U54CA112962 (to W.C. Hahn), and the Snyder Medical Research Foundation (to W.C. Hahn) NR 70 TC 35 Z9 36 U1 3 U2 18 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2013 VL 123 IS 6 BP 2551 EP 2563 DI 10.1172/JCI66343 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 160CD UT WOS:000320093100026 PM 23635776 ER PT J AU Nemlich, Y Greenberg, E Ortenberg, R Besser, MJ Barshack, I Jacob-Hirsch, J Jacoby, E Eyal, E Rivkin, L Prieto, VG Chakravarti, N Duncan, LM Kallenberg, DM Galun, E Bennett, DC Amariglio, N Bar-Eli, M Schachter, J Rechavi, G Markel, G AF Nemlich, Yael Greenberg, Eyal Ortenberg, Rona Besser, Michal J. Barshack, Iris Jacob-Hirsch, Jasmine Jacoby, Elad Eyal, Eran Rivkin, Ludmila Prieto, Victor G. Chakravarti, Nitin Duncan, Lyn M. Kallenberg, David M. Galun, Eitan Bennett, Dorothy C. Amariglio, Ninette Bar-Eli, Menashe Schachter, Jacob Rechavi, Gideon Markel, Gal TI MicroRNA-mediated loss of ADAR1 in metastatic melanoma promotes tumor growth SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DOUBLE-STRANDED-RNA; TO-INOSINE RNA; GENE-EXPRESSION; SYSTEMATIC IDENTIFICATION; ADENOSINE-DEAMINASE; CELL-PROLIFERATION; HUMAN CANCER; HUMAN BRAIN; TARGETS; DICER AB Some solid tumors have reduced posttranscriptional RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes, but the functional significance of this alteration has been unclear. Here, we found the primary RNA-editing enzyme ADAR1 is frequently reduced in metastatic melanomas. In situ analysis of melanoma samples using progression tissue microarrays indicated a substantial downregulation of ADAR1 during the metastatic transition. Further, ADAR1 knockdown altered cell morphology, promoted in vitro proliferation, and markedly enhanced the tumorigenicity in vivo. A comparative whole genome expression microarray analysis revealed that ADAR1 controls the expression of more than 100 microRNAs (miRNAs) that regulate many genes associated with the observed phenotypes. Importantly, we discovered that ADAR1 fundamentally regulates miRNA processing in an RNA binding-dependent, yet RNA editing-independent manner by regulating Dicer expression at the translational level via let-7. In addition, ADAR1 formed a complex with DGCR8 that was mutually exclusive with the DGCR8-Drosha complex that processes pri-miRNAs in the nucleus. We found that cancer cells silence ADAR1 by overexpressing miR-17 and miR-432, which both directly target the ADAR1 transcript. We further demonstrated that the genes encoding miR-17 and miR-432 are frequently amplified in melanoma and that aberrant hypomethylation of the imprinted DLK1-DIO3 region in chromosome 14 can also drive miR-432 overexpression. C1 [Nemlich, Yael; Greenberg, Eyal; Ortenberg, Rona; Besser, Michal J.; Schachter, Jacob; Markel, Gal] Ella Inst Melanoma, Ramat Gan, Israel. [Nemlich, Yael; Greenberg, Eyal; Ortenberg, Rona; Besser, Michal J.; Rechavi, Gideon; Markel, Gal] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Barshack, Iris] Sheba Med Ctr, Inst Pathol, Ramat Gan, Israel. [Jacob-Hirsch, Jasmine; Jacoby, Elad; Eyal, Eran; Amariglio, Ninette; Rechavi, Gideon] Sheba Med Ctr, Canc Res Ctr, Ramat Gan, Israel. [Jacoby, Elad] Sheba Med Ctr, Dept Pediat Hematooncol, Ramat Gan, Israel. [Rivkin, Ludmila; Galun, Eitan] Hadassah Hebrew Univ Hosp, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel. [Prieto, Victor G.; Chakravarti, Nitin] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. [Kallenberg, David M.; Bennett, Dorothy C.] Univ London, Biomed Sci Res Ctr, London, England. [Bar-Eli, Menashe] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Markel, Gal] Sheba Med Ctr, Talpiot Med Leadership Program, Ramat Gan, Israel. RP Markel, G (reprint author), Sheba Med Ctr, Ella Inst Melanoma, IL-52621 Ramat Gan, Israel. EM markel@post.tau.ac.il RI Bennett, Dorothy/C-2418-2008 OI Bennett, Dorothy/0000-0002-3639-7527 FU Israel Science Foundation [1489/10, 41/11.1]; Carol Fingerut Foundation for Cancer Research; Wellcome Trust [078327]; Planning and Budgeting Committee; Flight Attendants Medical Research Institute (FAMRI); Israel Ministry for Science and Technology; I-CORE ISF [41/11.1]; SFB DFG [841] FX G. Markel is supported by the Israel Science Foundation (grant 1489/10) and the Carol Fingerut Foundation for Cancer Research (grant 2008). D.M. Kallenberg is supported by Wellcome Trust (grant 078327). G. Rechavi is supported by the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation (grant no. 41/11.1), the Flight Attendants Medical Research Institute (FAMRI), the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation (grant no. 41/11.1), and the Israel Ministry for Science and Technology (Scientific Infrastructure Program, grant 2010). G. Rechavi holds the Djerassi Chair in Oncology, Tel Aviv University. E. Galun is supported by an I-CORE ISF grant (grant no. 41/11.1) and an SFB DFG grant (grant no. 841). The authors would like to thank Michael Aronson for his support in this work. This work was performed in partial fulfillment of the requirements for a Ph.D. degree for Yael Nemlich, Sackler Faculty of Medicine, Tel Aviv University. NR 63 TC 47 Z9 49 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2013 VL 123 IS 6 BP 2703 EP 2718 DI 10.1172/JCI62980 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 160CD UT WOS:000320093100039 PM 23728176 ER PT J AU Imel, ZE Laska, K Jakupcak, M Simpson, TL AF Imel, Zac E. Laska, Kevin Jakupcak, Matthew Simpson, Tracy L. TI Meta-Analysis of Dropout in Treatments for Posttraumatic Stress Disorder SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE PTSD; clinical trials; dropout; psychotherapy ID RANDOMIZED CONTROLLED-TRIAL; EYE-MOVEMENT DESENSITIZATION; NARRATIVE EXPOSURE THERAPY; COGNITIVE PROCESSING THERAPY; AFRICAN REFUGEE SETTLEMENT; BONA-FIDE PSYCHOTHERAPIES; SUBSTANCE USE DISORDERS; CHILDHOOD SEXUAL-ABUSE; PROLONGED EXPOSURE; IMAGINAL EXPOSURE AB Objective: Many patients drop out of treatments for posttraumatic stress disorder (PTSD); some clinicians believe that trauma-focused treatments increase dropout. Method: We conducted a meta-analysis of dropout among active treatments in clinical trials for PTSD (42 studies; 17 direct comparisons). Results: The average dropout rate was 18%, but it varied significantly across studies. Group modality and greater number of sessions, but not trauma focus, predicted increased dropout. When the meta-analysis was restricted to direct comparisons of active treatments, there were no differences in dropout. Differences in trauma focus between treatments in the same study did not predict dropout. However, trauma-focused treatments resulted in higher dropout compared with present-centered therapy (PCT), a treatment originally designed as a control but now listed as a research-supported intervention for PTSD. Conclusion: Dropout varies between active interventions for PTSD across studies, but variability is primarily driven by differences between studies. There do not appear to be systematic differences across active interventions when they are directly compared in the same study. The degree of clinical attention placed on the traumatic event does not appear to be a primary cause of dropout from active treatments. However, comparisons of PCT may be an exception to this general pattern, perhaps because of a restriction of variability in trauma focus among comparisons of active treatments. More research is needed comparing trauma-focused interventions to trauma-avoidant treatments such as PCT. C1 [Imel, Zac E.] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84112 USA. [Imel, Zac E.; Jakupcak, Matthew; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Laska, Kevin] Bedford VA Med Ctr, Bedford, MA USA. RP Imel, ZE (reprint author), Univ Utah, Dept Educ Psychol, 1705 Campus Ctr Dr RM 327, Salt Lake City, UT 84112 USA. EM zac.imel@utah.edu OI imel, zachary/0000-0001-9645-7184 FU NCRR NIH HHS [UL1 RR025014, UL1RR025014]; NIDA NIH HHS [R34 DA034860] NR 73 TC 50 Z9 50 U1 12 U2 44 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2013 VL 81 IS 3 BP 394 EP 404 DI 10.1037/a0031474 PG 11 WC Psychology, Clinical SC Psychology GA 150RA UT WOS:000319407300003 PM 23339535 ER PT J AU Suvak, MK Taft, CT Goodman, LA Dutton, MA AF Suvak, Michael K. Taft, Casey T. Goodman, Lisa A. Dutton, Mary Ann TI Dimensions of Functional Social Support and Depressive Symptoms: A Longitudinal Investigation of Women Seeking Help for Intimate Partner Violence SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE intimate partner violence; social support; depression; multilevel modeling; longitudinal ID POSTTRAUMATIC-STRESS-DISORDER; DOMESTIC VIOLENCE; BATTERED WOMEN; ADVOCACY INTERVENTION; PROTECTIVE FACTORS; ABUSIVE PARTNERS; MENTAL-HEALTH; METAANALYSIS; ADULTS; RISK AB Objective: We examined 4 separate dimensions of functional social support (tangible, appraisal, self-esteem, and belonging) as predictors of change in depression over 4.5 years in a sample of women reporting intimate partner violence. Method: Participants were recruited as they sought help for violence perpetrated by a current or former male partner. Three hundred eighty-eight participants completed the Interpersonal Support Evaluation List (Cohen, Mermelstein, Kamarck, & Hoberman, 1985), the Conflict Tactics Scale-2 (Straus, Hamby, Boney-McCoy, & Sugarman, 1996), and the Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977) at the baseline assessment. Participants were reevaluated on 9 follow-up assessment occasions over approximately 4.5 years, during which they completed the CES-D. Results: Growth curve analyses revealed that belonging, or the perceived availability of people one can do things with, was the only dimension that predicted changes in depressive symptoms when controlling for initial depressive symptom levels. Higher levels of belonging support reported at the baseline assessment were associated with larger decreases in depression. Conclusions: The findings of the current study suggest that interventions should consider ways to get survivors connected to informal social networks. Neither perceived availability of material aid nor availability of someone to talk about one's problems or serve as a positive comparison when comparing oneself to others was associated with decreased depression over time. Only perceived availability of people one can do things with (i.e., belonging support) exhibited salutary effects. C1 [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Taft, Casey T.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Goodman, Lisa A.] Boston Coll, Dept Counseling & Dev Psychol, Sch Educ, Chestnut Hill, MA 02167 USA. [Dutton, Mary Ann] Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20057 USA. RP Suvak, MK (reprint author), Suffolk Univ, Dept Psychol, 41 Temple St D609, Boston, MA 02114 USA. EM msuvak@suffolk.edu FU NIMH NIH HHS [1F32MH071011-1, F32 MH071011] NR 54 TC 4 Z9 4 U1 6 U2 28 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2013 VL 81 IS 3 BP 455 EP 466 DI 10.1037/a0031787 PG 12 WC Psychology, Clinical SC Psychology GA 150RA UT WOS:000319407300009 PM 23398492 ER PT J AU Palli, MBA Reyes-Habito, CM Lima, XT Kimball, AB AF Palli, Ma Beatrice Alora Reyes-Habito, Claire Marie Lima, Xinaida T. Kimball, Alexa B. TI A Single-Center, Randomized Double-Blind, Parallel-Group Study to Examine the Safety and Efficacy of 3mg Drospirenone/0.02mg Ethinyl Estradiol Compared With Placebo in the Treatment of Moderate Truncal Acne Vulgaris SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID CONTROLLED-TRIAL; 24/4 REGIMEN; NORGESTIMATE AB Background: Acne is a common disease of the face, chest and back, initially triggered by androgens. 3mg Drospirenone (DRSP)/0.02mg ethinyl estradiol (EE), an oral contraceptive and antiandrogen, has been effective in treatment studies of facial acne in women, but investigations on its efficacy for truncal acne are limited. Objective: In this study, we sought to evaluate the safety and efficacy of 3mg DRSP/0.02mg EE versus placebo in the treatment of truncal acne in women. Methods: Females, age 18-45, with 10 to 50 truncal acne lesions, were randomized in this double-blind study to 3mg DRSP/0.02mg EE (n=15) or placebo (n=10) administered in a 24/4 regimen given for 24 weeks. Noninflammatory, inflammatory and total truncal acne lesion counts were assessed from baseline to endpoint and mean percent change compared. Investigator Global Assessment (IGA) and Subject Global Assessment (SGA) were assessed based on scoring scales, and the percentage of subjects rated as success with clear (score 0) or almost clear (score 1) were computed. Results: The 3mg DRSP/0.02mg EE group had significant reductions in mean percent change in noninflammatory, inflammatory and total lesions by 52.1%, 53.2%, and 57.3%, respectively, compared to placebo with -9.2%, 18.2% and 17.0%, respectively, by week 24 (p = 0.02, 0.05 and 0.02, respectively). The percentage of subjects on 3mg DRSP/0.02mg EE rated as treatment success were 53.3% and 60% based on IGA and SGA respectively. The regimen was also well tolerated by patients. Conclusions: 3mg DRSP/0.02 mg EE is a safe and significantly effective treatment for moderate truncal acne. C1 [Palli, Ma Beatrice Alora; Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Palli, Ma Beatrice Alora; Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Palli, Ma Beatrice Alora; Reyes-Habito, Claire Marie; Kimball, Alexa B.] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA. [Lima, Xinaida T.] Univ Estadual Campinas, Dept Dermatol, Sao Paulo, Brazil. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Bayer FX This research was funded by Bayer. A.B.K. was a consultant of Bayer at the time of the study. NR 13 TC 10 Z9 11 U1 0 U2 1 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD JUN PY 2013 VL 12 IS 6 BP 633 EP 637 PG 5 WC Dermatology SC Dermatology GA 163NP UT WOS:000320344500005 PM 23839178 ER PT J AU Ladizinski, B Carter, JB Lee, KC Aaron, DM AF Ladizinski, Barry Carter, Joi B. Lee, Kachiu C. Aaron, Denise M. TI Diagnosis of Herpes Simplex Virus-Induced Erythema Multiforme Confounded by Previous Infection With Mycoplasma Pneumonia SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID GENITAL HERPES; SEROLOGY; ASSAY AB Erythema multiforme (EM) is an immune-mediated hypersensitivity reaction often related to viral infection or medications. Infection-induced EM is typically self-limited and commonly caused by herpes simplex virus (HSV) or Mycoplasma pneumoniae (MP); recurrent EM is almost always associated with HSV. We present a concise overview of diagnostic techniques for HSV and MR as repeatedly elevated MP titers in our case led to a delayed diagnosis of HSV-induced EM. C1 [Ladizinski, Barry] Duke Univ Hosp, Dept Dermatol, Durham, NC 27708 USA. [Carter, Joi B.] Mass Gen Hosp, Dept Dermatol, Boston, MA USA. [Lee, Kachiu C.] Brown Univ Hosp, Dept Dermatol, Providence, RI USA. [Aaron, Denise M.] Dartmouth Hitchcock Med Ctr, Dept Dermatol, Lebanon, NH 03766 USA. RP Ladizinski, B (reprint author), Duke Univ Hosp, Dept Dermatol, Durham, NC 27708 USA. EM barryladizinski@gmail.com NR 8 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD JUN PY 2013 VL 12 IS 6 BP 707 EP 709 PG 3 WC Dermatology SC Dermatology GA 163NP UT WOS:000320344500019 PM 23839193 ER PT J AU Martindale, JL AF Martindale, Jennifer L. TI IMAGING ABNORMALITIES ASSOCIATED WITH CARBON MONOXIDE TOXICITY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID BRAIN C1 [Martindale, Jennifer L.] Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Martindale, JL (reprint author), Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency Progra, 55 Fruit St, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2013 VL 44 IS 6 BP 1140 EP 1141 DI 10.1016/j.jemermed.2012.07.069 PG 2 WC Emergency Medicine SC Emergency Medicine GA 161TX UT WOS:000320217300014 PM 23478185 ER PT J AU Wen, LS Xu, J Steptoe, AP Sullivan, AF Walline, JH Yu, XZ Camargo, CA AF Wen, Leana S. Xu, Jun Steptoe, Anne P. Sullivan, Ashley F. Walline, Joseph H. Yu, Xuezhong Camargo, Carlos A., Jr. TI EMERGENCY DEPARTMENT CHARACTERISTICS AND CAPABILITIES IN BEIJING, CHINA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE international emergency medicine; China; Emergency Department classification; health policy; Emergency Department crowding ID MEDICINE AB Background: Emergency Departments (EDs) are a critical, yet heterogeneous, part of international emergency care. Objectives: We sought to describe the characteristics, resources, capabilities, and capacity of EDs in Beijing, China. Methods: Beijing EDs accessible to the general public 24 h per day/7 days per week were surveyed using the National ED Inventories survey instrument (vvvvvv.emnet-nedi.org). ED staff were asked about ED characteristics during the calendar year 2008. Results: Thirty-six EDs participated (88% response rate). All were located in hospitals and were independent hospital departments. Participating EDs saw a median of 80,000 patients (interquartile range 40,000-118,508). The vast majority (91%; 95% confidence interval [CI] 78-98%) had a contiguous layout, with medical and surgical care provided in one area. Most EDs (55%) saw only adults; 39% saw both adults and children, and 6% saw only children. Availability of technological and consultant resource in EDs was high. The typical ED length of stay was between land 6 h in 49% of EDs (95% CI 32-67%), whereas in the other half, patients reportedly remained for over 6 h; 36% (95% CI 21-54%) of respondents considered their ED over capacity. Conclusions: Beijing EDs have high volume, long length of stay, and frequent reports of EDs being over capacity. To meet its rapidly growing health needs in urban areas, China should consider improving urban ED capacity and training more Emergency Medicine specialists capable of efficiently staffing its crowded EDs. (C) 2013 Elsevier Inc. C1 [Wen, Leana S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Boston, MA 02114 USA. [Xu, Jun; Yu, Xuezhong] Beijing Union Med Coll Hosp, Dept Emergency Med, Beijing, Peoples R China. [Steptoe, Anne P.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Walline, Joseph H.] St Louis Univ, Div Emergency Med, St Louis, MO 63103 USA. RP Xu, J (reprint author), Beijing Union Med Coll Hosp, Dept Emergency Med, 1 Shuaifuyuan, Beijing, Peoples R China. OI Wen, Leana/0000-0003-0259-0537 NR 14 TC 2 Z9 2 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2013 VL 44 IS 6 BP 1174 EP 1179 DI 10.1016/j.jemermed.2012.07.083 PG 6 WC Emergency Medicine SC Emergency Medicine GA 161TX UT WOS:000320217300023 PM 23473821 ER PT J AU Chung, KC Kim, HM Haase, SC Lawton, J Ozer, K Waljee, JF Nellans, K Malay, S Shauver, MJ Rozental, TD Appleton, P Rodriguez, E Herder, L Wagner, K Blazar, P Earn, B Floyd, WE Leversedge, F Pico, KS Richards, MJ Ruch, DS Finley, S Kalliainen, LK Fletcher, JW Heinrich, CA Ward, CM Hill, BW Bamberger, B Robinson, C Palmer, B Ring, D Jupiter, JB Reddy, R Dennison, D Kakar, S Shin, A Scrabeck, T Hoyen, H Malone, K Sebastin, S Tay, PL Gaston, G Connell, B Neumeister, M Berry, NN Bueno, RA McAndrew, M Koechle, J Perey, B Zomar, M Wolf, JM Rodner, CM Cote, M Clark, T Lehman, T Carl, K Bozentka, D Levin, S Steinberg, D Horan, A Knox, D Hammert, W McIntyre, AW Friedrich, JB Allan, CH Hanel, DP Huang, JI Ko, JH Vedder, NB Boman, D Cooper, CL Grewal, R MacDermid, J Kelly, K Millman, K Li, ZY Koman, A Smith, B Bullard, D AF Chung, Kevin C. Kim, H. Myra Haase, Steven C. Lawton, Jeffrey Ozer, Kagan Waljee, Jennifer F. Nellans, Kate Malay, Sunitha Shauver, Melissa J. Rozental, Tamara D. Appleton, Paul Rodriguez, Edward Herder, Lindsay Wagner, Katiri Blazar, Philip Earn, Brandon Floyd, W. Emerson Leversedge, Fraser Pico, Katherine S. Richards, Marc J. Ruch, David S. Finley, Suzanne Kalliainen, Loree K. Fletcher, James W. Heinrich, Cherrie A. Ward, Christian M. Hill, Brian W. Bamberger, Brent Robinson, Carla Palmer, Brandi Ring, David Jupiter, Jesse B. Reddy, Rajesh Dennison, David Kakar, Sanjeev Shin, Alexander Scrabeck, Tyson Hoyen, Harry Malone, Kevin Sebastin, Sandeep Tay, Pub Ling Gaston, Glenn Connell, Benjamin Neumeister, Michael Berry, Nada N. Bueno, Reuben A., Jr. McAndrew, Mark Koechle, Jennifer Perey, Bertrand Zomar, Mauri Wolf, Jennifer Moriatis Rodner, Craig M. Cote, Mark Clark, Tod Lehman, Thomas Carl, Kathy Bozentka, David Levin, Scott Steinberg, David Horan, Annamarie Knox, Denise Hammert, Warren McIntyre, Allison W. Friedrich, Jeffrey B. Allan, Christopher H. Hanel, Douglas P. Huang, Jerry I. Ko, Jason H. Vedder, Nicholas B. Boman, David Cooper, Claudette L. Grewal, Ruby MacDermid, Joy Kelly, Kate Millman, Kristie Li, Zhongyu Koman, Andrew Smith, Beth Bullard, Debra CA Wrist Radius Injury Surgical Trial TI Reflections 1 Year Into the 21-Center National Institutes of Health-Funded WRIST Study: A Primer on Conducting a Multicenter Clinical Trial SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal radius fracture; randomized clinical trials; multicenter trials ID DISTAL RADIUS FRACTURES; STATES MEDICARE POPULATION; UNITED-STATES; SEASONAL-VARIATION; OLDER-PEOPLE; EXPERIENCE; BARRIERS; OUTCOMES; WOMEN; RECRUITMENT AB The Wrist and Radius Injury Surgery Trial (WRIST) study group is a collaboration of 21 hand surgery centers in the United States, Canada, and Singapore, to showcase the interest and capability of hand surgeons to conduct a multicenter clinical trial. The WRIST study group was formed in response to the seminal systematic review by Margaliot et al and the Cochrane report that indicated marked deficiency in the quality of evidence in the distal radius fracture literature. Since the initial description of this fracture by Cones in 1814, over 2,000 studies have been published on this subject; yet, high-level studies based on the principles of evidence-based medicine are lacking. As we continue to embrace evidence-based medicine to raise the quality of research, the lessons learned during the organization and conduct of WRIST can serve as a template for others contemplating similar efforts. This article traces the course of WRIST by sharing the triumphs and, more important, the struggles faced in the first year of this study. (Copyright (C) 2013 by the American Society for Surgery of the Hand All rights reserved.) C1 [Chung, Kevin C.; Kim, H. Myra; Haase, Steven C.; Lawton, Jeffrey; Ozer, Kagan; Waljee, Jennifer F.; Nellans, Kate; Malay, Sunitha; Shauver, Melissa J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rozental, Tamara D.; Appleton, Paul; Rodriguez, Edward; Herder, Lindsay; Wagner, Katiri] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Blazar, Philip; Earn, Brandon; Floyd, W. Emerson] Brigham & Womens Hosp, Boston, MA 02115 USA. [Leversedge, Fraser; Pico, Katherine S.; Richards, Marc J.; Ruch, David S.; Finley, Suzanne] Duke Univ, Durham, NC 27706 USA. [Bamberger, Brent; Robinson, Carla; Palmer, Brandi] Kettering Hlth Network, Kettering, England. [Ring, David; Jupiter, Jesse B.; Reddy, Rajesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dennison, David; Kakar, Sanjeev; Shin, Alexander; Scrabeck, Tyson] Mayo Clin, Rochester, MN USA. [Sebastin, Sandeep; Tay, Pub Ling] Natl Univ Singapore, Singapore 117548, Singapore. [Neumeister, Michael; Berry, Nada N.; Bueno, Reuben A., Jr.; McAndrew, Mark; Koechle, Jennifer] So Illinois Univ, Carbondale, IL 62901 USA. [Perey, Bertrand; Zomar, Mauri] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Wolf, Jennifer Moriatis; Rodner, Craig M.; Cote, Mark] Univ Connecticut, Storrs, CT USA. [Clark, Tod] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. [Lehman, Thomas; Carl, Kathy] Univ Oklahoma, Norman, OK 73019 USA. [Bozentka, David; Levin, Scott; Steinberg, David; Horan, Annamarie; Knox, Denise] Univ Penn, Philadelphia, PA 19104 USA. [Hammert, Warren; McIntyre, Allison W.] Univ Rochester, Rochester, NY 14627 USA. [Friedrich, Jeffrey B.; Allan, Christopher H.; Hanel, Douglas P.; Huang, Jerry I.; Ko, Jason H.; Vedder, Nicholas B.; Boman, David; Cooper, Claudette L.] Univ Washington, Seattle, WA 98195 USA. [Grewal, Ruby; MacDermid, Joy; Kelly, Kate; Millman, Kristie] Univ Western Ontario, London, ON N6A 3K7, Canada. [Li, Zhongyu; Koman, Andrew; Smith, Beth; Bullard, Debra] Wake Forest Univ, Winston Salem, NC 27109 USA. RP Chung, KC (reprint author), Univ Michigan Hlth Syst, Sect Plast Surg, Taubman Ctr 2130, SPC 5340,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM kecchung@med.umich.edu RI MacDermid, Joy/H-7837-2013; Waljee, Jennifer/A-1319-2014; OI MacDermid, Joy/0000-0001-9311-7379; Shauver, Melissa/0000-0001-5882-5986; Shin, Alexander/0000-0001-9658-8192 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute on Aging [R01 AR062066]; Midcareer Investigator Award in Patient-Oriented Research [K24 AR053120] FX Supported in part by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging (R01 AR062066) and a Midcareer Investigator Award in Patient-Oriented Research (K24 AR053120) (to K.C.C.). NR 33 TC 0 Z9 0 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2013 VL 38A IS 6 BP 1194 EP 1201 DI 10.1016/j.jhsa.2013.02.027 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 163MV UT WOS:000320342500022 ER PT J AU Hageman, MGJS Guitton, TG Ring, D AF Hageman, Michiel G. J. S. Guitton, Thierry G. Ring, David CA Sci Variation Grp TI How Surgeons Make Decisions When the Evidence Is Inconclusive SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Decision making; evidence-based medicine; treatment ID TRIAL AB Purpose To address the factors that surgeons use to decide between 2 options for treatment when the evidence is inconclusive. Methods We tested the null hypothesis that the factors surgeons use do not vary by training, demographics, and practice. A total of 337 surgeons rated the importance of 7 factors when deciding between treatment and following the natural history of the disease and 12 factors when deciding between 2 operative treatments using a 5-point Likert scale between "very important" and "very unimportant." Results According to the percentages of statements rated very important or somewhat important, the most popular factors influencing recommendations when evidence is inconclusive between treatment and following the natural course of the illness were "works in my hands," "familiarity with the treatment," and "what my mentor taught me." The most important factors when evidence shows no difference between 2 surgeries were "fewer complications," "quicker recovery," "burns fewer bridges," "works in my hands" and "familiarity with the procedure." Europeans rated "works in my hands" and "cheapest/most resourceful" of significantly greater importance and "what others are doing," "highest reimbursement," and "shorter procedure" of significantly lower importance than surgeons in the United States. Observers with fewer than 10 years in independent practice rated "what my mentor taught me," "what others are doing" and "highest reimbursement" of significantly lower importance compared to observers with 10 or more years in independent practice. Conclusions Surgeons deciding between 2 treatment options, when the evidence is inconclusive, fall back to factors that relate to their perspective and reflect their culture and circumstances, more so than factors related to the patient's perspective, although this may be different for younger surgeons. Clinical relevance Hand surgeons might benefit from consensus fallback preferences when evidence is inconclusive. It is possible that falling back to personal comfort makes us vulnerable to unhelpful commercial and societal influences. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Hageman, Michiel G. J. S.; Guitton, Thierry G.; Ring, David; Sci Variation Grp] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Fernandes, C/F-9839-2012; Page, Richard/K-6327-2015; OI Miller, Anna/0000-0002-7056-8502; Beeres, Frank/0000-0002-7277-3438; harvey, edward/0000-0003-3934-8920; Swiontkowski, Marc/0000-0001-7036-1782; Aita, Marcio Aurelio Aita/0000-0002-9062-265X; Jubel, Axel/0000-0003-4402-4816; Goldfarb, Charles/0000-0001-9672-8853; Borris, Lars/0000-0002-0527-1518; Guitton, Thierry/0000-0002-2599-1985; Streubel, Philipp/0000-0002-4585-1779; Fernandes, C/0000-0003-0146-6091; Page, Richard/0000-0002-2225-7144; Kanakaris, Nikolaos/0000-0002-1695-1519; Frihagen, Frede/0000-0002-4811-669X; Ladd, Amy/0000-0003-0948-1034 FU Marti-Keunig Eckhart Stichting; Anna Foundation FX M.G.H. is supported by Dutch research grants from Marti-Keunig Eckhart Stichting and Anna Foundation. NR 12 TC 11 Z9 11 U1 0 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2013 VL 38A IS 6 BP 1202 EP 1208 DI 10.1016/j.jhsa.2013.02.032 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 163MV UT WOS:000320342500023 PM 23647639 ER PT J AU Raizman, NM Ring, D Hammert, WC AF Raizman, Noah M. Ring, David Hammert, Warren C. TI Evidence-Based Reviews of Hand and Upper Extremity Surgery SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Hand & Upper Extrem Inst Greater Washington, Washington, DC USA. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Hammert, Warren C.] Univ Rochester, Med Ctr, Dept Orthopaed Surg, Rochester, NY 14642 USA. RP Hammert, WC (reprint author), Univ Rochester, Med Ctr, Dept Orthopaed Surg, 601 Elmwood Ave,Box 665, Rochester, NY 14642 USA. EM warren_hammert@urmcrochester.edu 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2013 VL 38A IS 6 BP 1247 EP 1251 DI 10.1016/j.jhsa.2013.02.031 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 163MV UT WOS:000320342500034 PM 23591022 ER PT J AU Suswam, EA Shacka, JJ Walker, K Lu, L Li, XL Si, Y Zhang, XW Zheng, L Nabors, LB Cao, HP King, PH AF Suswam, Esther A. Shacka, John J. Walker, Kiera Lu, Liang Li, Xuelin Si, Ying Zhang, Xiaowen Zheng, Lei Nabors, L. Burt Cao, Heping King, Peter H. TI Mutant tristetraprolin: a potent inhibitor of malignant glioma cell growth SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE RNA stability; VEGF; IL-6; IL-8; Post-transcriptional gene regulation ID MESSENGER-RNA STABILITY; ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; SIGNALING PATHWAY; RICH ELEMENTS; UP-REGULATION; BRF PROTEINS; CANCER CELLS; BINDING; HUR AB Malignant gliomas rely on the production of certain critical growth factors including VEGF, interleukin (IL)-6 and IL-8, to fuel rapid tumor growth, angiogenesis, and treatment resistance. Post-transcriptional regulation through adenine and uridine-rich elements of the 3' untranslated region is one mechanism for upregulating these and other growth factors. In glioma cells, we have shown that the post-transcriptional machinery is optimized for growth factor upregulation secondary to overexpression of the mRNA stabilizer, HuR. The negative regulator, tristetraprolin (TTP), on the other hand, may be suppressed because of extensive phosphorylation. Here we test that possibility by analyzing the phenotypic effects of a mutated form of TTP (mt-TTP) in which 8 phosphoserine residues were converted to alanines. We observed a significantly enhanced negative effect on growth factor expression in glioma cells at the post-transcriptional and transcriptional levels. The protein became stabilized and displayed significantly increased antiproliferative effects compared to wild-type TTP. Macroautophagy was induced with both forms of TTP, but inhibition of autophagy did not affect cell viability. We conclude that glioma cells suppress TTP function through phosphorylation of critical serine residues which in turn contributes to growth factor upregulation and tumor progression. C1 [Suswam, Esther A.; Walker, Kiera; Lu, Liang; Li, Xuelin; Si, Ying; Zheng, Lei; Nabors, L. Burt; King, Peter H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Shacka, John J.; Lu, Liang; Li, Xuelin; Si, Ying; King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Zhang, Xiaowen] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Cao, Heping] ARS, Utilizat Res Unit, So Reg Res Ctr, USDA, New Orleans, LA 70124 USA. [King, Peter H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [King, Peter H.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA. RP Suswam, EA (reprint author), Univ Alabama Birmingham, Dept Neurol, 1720 2nd Ave South,WTI410C, Birmingham, AL 35294 USA. EM easuswam@uab.edu; pking@uab.edu FU Department of Veterans Affairs Research; National Institutes of Health [RO1 NS064133, CA131468, NS057664] FX Grant support: Department of Veterans Affairs Research, Merit Review grants (PHK and JJS), National Institutes of Health grants (RO1 NS064133 to PHK, CA131468 to EAS, and NS057664 to LL). The sponsors played no role in the design of experiments, interpretation of results, or writing this manuscript. NR 50 TC 11 Z9 11 U1 0 U2 13 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 JUN PY 2013 VL 113 IS 2 BP 195 EP 205 DI 10.1007/s11060-013-1112-8 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 162CD UT WOS:000320241100005 PM 23525947 ER PT J AU Backes, DM Siddiq, A Cox, DG Calboli, FCF Gaziano, JM Ma, J Stampfer, M Hunter, DJ Camargo, CA Michaud, DS AF Backes, Danielle M. Siddiq, Afshan Cox, David G. Calboli, Federico C. F. Gaziano, J. Michael Ma, Jing Stampfer, Meir Hunter, David J. Camargo, Carlos A. Michaud, Dominique S. TI Single-nucleotide polymorphisms of allergy-related genes and risk of adult glioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Brain tumors; Glioma; Allergies; Single-nucleotide polymorphisms; Cohort studies ID IGE LEVELS; INNATE IMMUNITY; ASTHMA; SUSCEPTIBILITY; GLIOBLASTOMA; METAANALYSIS; ASSOCIATION; VARIANTS AB Previous studies have shown an inverse association between allergies and glioma risk; however, results for associations between single nucleotide polymorphisms (SNPs) of allergy-related genes and glioma risk have been inconsistent and restricted to a small number of SNPs. The objective of this study was to examine the association between 166 SNPs of 21 allergy-related genes and glioma risk in a nested case-control study of participants from three large US prospective cohort studies. Blood collection took place between 1982 and 1994 among the 562 included Caucasian participants (143 cases and 419 matched controls) prior to case diagnosis. Custom Illumina assay chips were used for genotyping. Logistic regression analyses, controlling for age and study cohort, were used to determine associations between each SNP and glioma risk. Statistically significant associations were found between rs2494262 and rs2427824 of the FCER1A gene, which encodes the alpha chain of the high affinity immunoglobulin E receptor, and glioma risk (nominal trend p values 0.01 and 0.03, respectively). Significant associations were also found between SNPs in IL10, ADAM33, NOS1 and IL4R and glioma risk. However, our analyses were not corrected for multiple comparisons and need to be interpreted with caution. Our findings with FCER1A SNPs provide further support for the link between allergies and risk of glioma. C1 [Backes, Danielle M.; Michaud, Dominique S.] Brown Univ, Brown Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Siddiq, Afshan; Cox, David G.; Calboli, Federico C. F.; Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, London SW7 2AZ, England. [Cox, David G.] UCBL1, CNRS, INSERM, U1052,UMR 5286,Lyon Canc Res Ctr, F-69008 Lyon, France. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Ma, Jing; Stampfer, Meir; Hunter, David J.; Camargo, Carlos A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ma, Jing; Stampfer, Meir; Hunter, David J.; Camargo, Carlos A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Michaud, DS (reprint author), Brown Univ, Brown Publ Hlth, Dept Epidemiol, POB G-S121-2, Providence, RI 02912 USA. EM dominique_michaud@brown.edu RI Michaud, Dominique/I-5231-2014; Cox, David/A-2023-2009 OI Cox, David/0000-0002-2152-9259 FU National Institutes of Health [R01 CA114205, P01 CA097193, P01 CA087969, P01 CA055075] FX We thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This work was supported by the National Institutes of Health [grant numbers R01 CA114205 to DSM, P01 CA097193 to JMG, P01 CA087969 to MS, P01 CA055075 to Dr. Willett]. This research complies with the current laws of the country in which it was performed. NR 29 TC 7 Z9 7 U1 0 U2 5 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 JUN PY 2013 VL 113 IS 2 BP 229 EP 238 DI 10.1007/s11060-013-1122-6 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 162CD UT WOS:000320241100008 PM 23525950 ER PT J AU Shonka, NA Theeler, B Cahill, D Yung, A Smith, L Lei, XD Gilbert, MR AF Shonka, Nicole A. Theeler, Brett Cahill, Daniel Yung, Alfred Smith, Lynette Lei, Xiudong Gilbert, Mark R. TI Outcomes for patients with anaplastic astrocytoma treated with chemoradiation, radiation therapy alone or radiation therapy followed by chemotherapy: a retrospective review within the era of temozolomide SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Anaplastic astrocytoma; Radiation therapy; Chemotherapy; Treatment ID MALIGNANT GLIOMAS; PHASE-III; GLIOBLASTOMA; RADIOTHERAPY; NECROSIS; BRAIN; DIBROMODULCITOL; SURVIVAL; TRIAL AB Treatment for anaplastic astrocytoma (AA) is controversial. To assess three primary treatment approaches, patients from a single institution were retrospectively evaluated. To represent modern treatment selection, patients diagnosed with AA from December 2003 to December 2009 were selected. Those with insufficient data, incomplete pathology, and transformation or reclassification to glioblastoma in fewer than 6 months were excluded. A total of 163 patients were included in the final analyses. Median follow-up time was 4.2 years (range 0.5-7.8 years). Median age and Karnofsky performance status at diagnosis were 39.2 years and 90, respectively. 23.6 % of patients underwent biopsy, and 72.2 % underwent resection. Approximately 31 % received concurrent chemoradiation (CRT), 26.1 % had radiation therapy alone (RT), 38.2 % had radiation therapy followed by chemotherapy (RT-C), and 3 % were treated only with chemotherapy. Temozolomide was used almost exclusively during CRT (94.2 %) and adjuvantly. A median of 9.5 cycles of adjuvant chemotherapy was given. The combination of radiation and chemotherapy, either concurrent or sequential trended toward a higher rate of radiation necrosis. Median progression free survival (PFS) favored RT (not reached) over CRT (1.5 years) and RT-C (3.6 years) adjusted for pairwise comparison (p = 0.033, p = 0.050). Median overall survival (OS) was 5.7 years, and did not differ significantly by treatment group. OS for patients with AA did not vary by initial treatment selection. Although the longer PFS in those receiving RT versus CRT may be confounded by pseudoprogression, the equivalent OS among groups supports RT. C1 [Shonka, Nicole A.; Smith, Lynette] Univ Nebraska Med Ctr, Nebraska Med Ctr 987680, Omaha, NE 68198 USA. [Theeler, Brett] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Cahill, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yung, Alfred; Lei, Xiudong; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Shonka, NA (reprint author), Univ Nebraska Med Ctr, Nebraska Med Ctr 987680, Omaha, NE 68198 USA. EM nshonka@unmc.edu RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Cahill, Daniel/0000-0003-2552-6546 FU NCI NIH HHS [P30 CA016672] NR 21 TC 12 Z9 13 U1 0 U2 5 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 JUN PY 2013 VL 113 IS 2 BP 305 EP 311 DI 10.1007/s11060-013-1116-4 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 162CD UT WOS:000320241100016 PM 23526410 ER PT J AU Prabhakar, AM Harvey, HB Hirsch, JA Wicky, S Oklu, R AF Prabhakar, Anand M. Harvey, H. Benjamin Hirsch, Joshua A. Wicky, Stephan Oklu, Rahmi TI Medical Device Excise Tax: Implications for Interventional Radiologists SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID HEALTH REFORM C1 [Prabhakar, Anand M.; Harvey, H. Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging, Boston, MA 02114 USA. [Wicky, Stephan; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurointervent Radiol, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, 55 Fruit St,GRB 290A, Boston, MA 02114 USA. EM rahmioklu@gmail.com NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2013 VL 24 IS 6 BP 795 EP 796 DI 10.1016/j.jvir.2013.02.027 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 158FY UT WOS:000319956100006 PM 23707088 ER PT J AU Grady, CD Schwarz, EB Emeremni, CA Yabes, J Akers, A Zite, N Borrero, S AF Grady, Cynthia D. Schwarz, Eleanor Bimla Emeremni, Chetachi A. Yabes, Jonathan Akers, Aletha Zite, Nikki Borrero, Sonya TI Does a History of Unintended Pregnancy Lessen the Likelihood of Desire for Sterilization Reversal? SO JOURNAL OF WOMENS HEALTH LA English DT Article ID TUBAL-STERILIZATION; UNITED-STATES; FEMALE STERILIZATION; REGRET AB Background: Unintended pregnancy has been significantly associated with subsequent female sterilization. Whether women who are sterilized after experiencing an unintended pregnancy are less likely to express desire for sterilization reversal is unknown. Methods: This study used national, cross-sectional data collected by the 2006-2010 National Survey of Family Growth. The study sample included women ages 15-44 who were surgically sterile from a tubal sterilization at the time of interview. Multivariable logistic regression was used to examine the relationship between a history of unintended pregnancy and desire for sterilization reversal while controlling for potential confounders. Results: In this nationally representative sample of 1,418 women who were sterile from a tubal sterilization, 78% had a history of at least one unintended pregnancy and 28% expressed a desire to have their sterilization reversed. In unadjusted analysis, having a prior unintended pregnancy was associated with higher odds of expressing desire for sterilization reversal (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.15-2.79). In adjusted analysis controlling for sociodemographic factors, unintended pregnancy was no longer significantly associated with desire for reversal (OR: 1.46; 95% CI: 0.91-2.34). Conclusion: Among women who had undergone tubal sterilization, a prior history of unintended pregnancy did not decrease desire for sterilization reversal. C1 [Grady, Cynthia D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Schwarz, Eleanor Bimla; Yabes, Jonathan; Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Schwarz, Eleanor Bimla] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Emeremni, Chetachi A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Yabes, Jonathan; Akers, Aletha] Univ Pittsburgh, Res Ctr, Hlth Care Data Ctr, Pittsburgh, PA 15213 USA. [Zite, Nikki] Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Borrero, S (reprint author), Univ Pittsburgh, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu OI Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU National Center for Research Resources; National Center For Advancing Translational Sciences of the National Institutes of Health [2KL2 RR024154-06] FX Dr. Borrero's effort on this project was supported by the National Center for Research Resources and the National Center For Advancing Translational Sciences of the National Institutes of Health through Grant Number 2KL2 RR024154-06. NR 20 TC 3 Z9 3 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 JUN PY 2013 VL 22 IS 6 BP 501 EP 506 DI 10.1089/jwh.2012.3885 PG 6 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 161BE UT WOS:000320164600006 PM 23621776 ER PT J AU Mauguen, A Pignon, JP Burdett, S Domerg, C Fisher, D Paulus, R Mandrekar, SJ Belani, CP Shepherd, FA Eisen, T Pang, H Collette, L Sause, WT Dahlberg, SE Crawford, J O'Brien, M Schild, SE Parmar, M Tierney, JF Le Pechoux, C Michiels, S AF Mauguen, Audrey Pignon, Jean-Pierre Burdett, Sarah Domerg, Caroline Fisher, David Paulus, Rebecca Mandrekar, Samithra J. Belani, Chandra P. Shepherd, Frances A. Eisen, Tim Pang, Herbert Collette, Laurence Sause, William T. Dahlberg, Suzanne E. Crawford, Jeffrey O'Brien, Mary Schild, Steven E. Parmar, Mahesh Tierney, Jayne F. Le Pechoux, Cecile Michiels, Stefan CA Surrogate Lung Project Collaborati TI Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data SO LANCET ONCOLOGY LA English DT Article ID PROGRESSION-FREE SURVIVAL; COLORECTAL-CANCER; CLINICAL-TRIALS; TUMOR RESPONSE; VALIDATION; TIME AB Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods We analysed individual patients' data from 15071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (square(2)=0.83, 95% CI 0.83-0.83 in trials without radiotherapy, and 0.87, 0.87-0.87 in trials with radiotherapy) and excellent at trial level (R-2=0.92, 95% CI 0.88-0.95 in trials without radiotherapy and 0.99, 0.98-1.00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (square(2) range 0.77-0.85, dependent on the regimen being assessed) and trial level (R-2 range 0.89-0.97). In studies with data on locoregional control, individual-level correlations were good (square(2)=0.71, 95% CI 0.71-0.71 for concurrent chemotherapy and square(2)=0.61, 0.61-0.61 for modified vs standard radiotherapy) and trial-level correlations very good (R-2=0.85, 95% CI 0.77-0.92 for concurrent chemotherapy and R-2=0.95, 0.91-0.98 for modified vs standard radiotherapy). Interpretation We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted. C1 [Mauguen, Audrey; Pignon, Jean-Pierre; Domerg, Caroline; Michiels, Stefan] Inst Gustave Roussy, Metaanal Unit, Dept Biostat & Epidemiol, F-94805 Villejuif, France. [Le Pechoux, Cecile] Inst Gustave Roussy, Dept Radiotherapy, F-94805 Villejuif, France. [Burdett, Sarah; Fisher, David; Parmar, Mahesh; Tierney, Jayne F.] MRC Clin Trials Unit, London, England. [Paulus, Rebecca] RTOG Stat Ctr, Philadelphia, PA USA. [Mandrekar, Samithra J.; Schild, Steven E.] Mayo Clin, Rochester, MN USA. [Mandrekar, Samithra J.; Schild, Steven E.] North Cent Canc Treatment Grp, Rochester, MN USA. [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Shepherd, Frances A.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Shepherd, Frances A.] NCIC Clin Trials Grp, Toronto, ON, Canada. [Eisen, Tim] Cambridge Biomed Res Ctr, Cambridge, England. [Pang, Herbert; Crawford, Jeffrey] Duke Univ, Canc & Leukemia Grp B, Ctr Stat, Durham, NC USA. [Collette, Laurence] EORTC Headquarters, Brussels, Belgium. [Sause, William T.] Intermt Med Ctr, Murray, UT USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [O'Brien, Mary] Royal Marsden Hosp, London SW3 6JJ, England. [Michiels, Stefan] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Michiels, Stefan] Univ Paris 11, Paris, France. RP Pignon, JP (reprint author), Inst Gustave Roussy, Metaanal Unit, Dept Biostat & Epidemiol, 114 Rue Edoudard Vaillant, F-94805 Villejuif, France. EM jppignon@igr.fr RI koning, caro/A-5339-2008; Michiels, Stefan/L-1516-2013; Higgins, Julian/H-4008-2011; OI Michiels, Stefan/0000-0002-6963-2968; Higgins, Julian/0000-0002-8323-2514; Belani, Chandra/0000-0001-5049-5329; schild, steven/0000-0002-2850-4126; Mauguen, Audrey/0000-0003-3236-6093; DAUTZENBERG, Bertrand/0000-0001-6937-8907 FU Programme Hospitalier de Recherche Clinique; Ligue Nationale Contre le Cancer; British Medical Research Council; Sanofi Aventis; Sanofi-Aventis FX Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, Sanofi Aventis.; This study was sponsored by Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, and Sanofi-Aventis. We thank the participating collaborative groups: Study Group of Adjuvant Chemotherapy for Lung Cancer, Arbeitsgemeinschaft Radioonkologie der Deutschen Krebsgesellschaft, Groupe d'Etude et de Traitement des Cancers Bronchiques, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, European Organization for Research and Treatment of Cancer, Groupe d'Oncologie Thoracique Lyon-Saint-Etienne-Groupe Francais de Pneumo-Cancerologie, Japan Clinical Oncology Group, Japan Lung Cancer Research Group, Medical Research Council, North Central Cancer Treatment Group, National Cancer Institute of Canada Clinical Trial Group, Radiation Therapy Oncology Group, and West Japan Study Group for Lung Cancer Surgery, and the clinical investigators of the trials and the patients. NR 28 TC 41 Z9 41 U1 0 U2 10 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 JUN PY 2013 VL 14 IS 7 BP 619 EP 626 DI 10.1016/S1470-2045(13)70158-X PG 8 WC Oncology SC Oncology GA 163XH UT WOS:000320371100048 PM 23680111 ER PT J AU Marak, CP Dorokhova, O Guddati, AK AF Marak, Creticus P. Dorokhova, Olena Guddati, Achuta K. TI Solitary fibrous tumor of the pleura SO MEDICAL ONCOLOGY LA English DT Article DE Solitary; Fibrous tumor; Pleura; Hemangiopericytoma ID DOEGE-POTTER-SYNDROME; SURGICAL-TREATMENT; LOCALIZED BENIGN; MESOTHELIOMA; HYPOGLYCEMIA; EXPRESSION; DIAGNOSIS; RESECTION; GIANT AB Solitary fibrous tumor of the pleura (SFTP) is a rare tumor of mesenchymal origin which can grow to a large size and present with symptoms of cough and pleuritic chest pain. No specific etiological factors for SFTPs are known and they may grow undetected for several years. These tumors are usually benign and may mimic a variety of malignancies. SFTPs are often detected as peripheral opacities on chest X-ray. Unfortunately, fine needle aspiration rarely provides adequate information for a definitive diagnosis. Imaging with computed tomography provides details about the size and extent of any invasion into adjacent tissues. Surgical resection is the mainstay of treatment, and immunohistochemistry of the resected tumor often provides confirmation of the diagnosis. Some SFTPs have been observed to be malignant, and surgical intervention is often lifesaving. There is no adequate data to support the usage of radiotherapy and chemotherapy in the treatment of SFTPs. This tumor exemplifies malignancies which require surgical resection to preempt worse outcomes. Awareness of their presentation and clinical course may help the clinician provide a prompt referral to the thoracic surgeon for resection. C1 [Marak, Creticus P.] Yeshiva Univ, Albert Einstein Coll Med, Montefiore Hosp, Div Pulm & Crit Care Med, New York, NY 10033 USA. [Dorokhova, Olena] Yeshiva Univ, Albert Einstein Coll Med, Montefiore Hosp, Dept Pathol, New York, NY 10033 USA. [Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Internal Med, Boston, MA 02115 USA. RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Internal Med, 50 Fruit St, Boston, MA 02115 USA. EM aguddati@partners.org NR 42 TC 3 Z9 5 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD JUN PY 2013 VL 30 IS 2 AR UNSP 573 DI 10.1007/s12032-013-0573-0 PG 6 WC Oncology SC Oncology GA 151HD UT WOS:000319450400080 PM 23576139 ER PT J AU Shaheen, S Guddati, AK AF Shaheen, Shagufta Guddati, Achuta K. TI Secondary mucosa-associated lymphoid tissue (MALT) lymphoma of the colon SO MEDICAL ONCOLOGY LA English DT Article DE MALT; Secondary; Colon; Adenocarcinoma; Lymphoma ID HELICOBACTER-PYLORI ERADICATION; OF-THE-LITERATURE; GASTRIC LYMPHOMA; RECTUM; RADIOTHERAPY; REGRESSION; PROGNOSIS; FEATURES AB Mucosa-associated lymphoid tissue (MALT)type lymphomas most commonly occur in the stomach and have been associated with Helicobacter pylori infection. However, MALT-type lymphoma of the colon is a rare entity. It commonly manifests with symptoms of weight loss, low-grade fever, constipation, melena, and hematochezia. Unlike gastric lymphoma, it is difficult to detect MALT-type lymphoma of the colon by imaging. Colonoscopy may reveal lesions whose biopsy most commonly shows abundant B lymphocytes. There is no universal immunohistochemistry profile for MALT-type lymphoma but CD 20 staining is commonly seen. Trisomies and translocations have been described and their presence has been correlated with treatment response. Due to the rarity of colonic MALT-type lymphoma, no standard guidelines are available for its management. It often occurs individually and rarely occurs simultaneously with concurrent colon adenocarcinoma. This case report describes the presentation and clinical course of a secondary MALT-type lymphoma in a patient who underwent colectomy for a prior colon adenocarcinoma. C1 [Shaheen, Shagufta; Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, 50 Fruit St, Boston, MA 02115 USA. EM aguddati@partners.org NR 24 TC 2 Z9 2 U1 0 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD JUN PY 2013 VL 30 IS 2 AR UNSP 502 DI 10.1007/s12032-013-0502-2 PG 4 WC Oncology SC Oncology GA 151HD UT WOS:000319450400011 PM 23423787 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Workload and transmission data for the installation of a digital breast tomosynthesis system SO MEDICAL PHYSICS LA English DT Article DE radiation protection; x rays; shielding; workload; transmission; breast tomosynthesis ID MAMMOGRAPHY; FACILITIES; SCATTER; KVP AB Purpose: Digital breast tomosynthesis (DBT) differs from conventional mammography in target/filter, kVp range, and imaging geometry. The aim of this study was to assess the breast input exposure of a DBT system by completing a workload survey of DBT installations, and to determine the parameters alpha, beta, and gamma in the Archer equation for the primary radiation generated by the clinical workload distributions. Methods: The authors conducted a retrospective survey of the x-ray breast imaging performed between September 2011 and September 2012 in three clinical DBT rooms equipped with Selenia Dimensions systems (Hologic Inc., Bedford, MA). A total of 343 examinations were analyzed to calculate the workload (mA-minute) and the primary air kerma at 1 m from the source (K-1). Transmission curves were calculated for the primary radiation generated by the workload distributions of the DBT rooms, and were fitted to the Archer equation. Results: There were large variations in patient volume and workload in the three examination rooms. In all these rooms, the average tube voltage (kVp) was about 31, the average K-1 per patient was 16-21 mGy, and the average mA-minute per patient was 1.4-2.2 times higher than that of the mammography room described in NCRP Report No. 147. Most DBT screening examinations consisted of four two-dimensional mammographic views plus four tomosynthesis scans; the numbers of views acquired in diagnostic examinations varied widely. Tomosynthesis scans contributed about 30% of total mA-minute and about 50% of K-1. For the primary radiation generated by the clinical workload distributions, a was similar to that of 40-45 kVp W/Al (target/filter), and alpha + beta was similar to that of 30 kVp W/Al. Conclusions: The workload (mA-minute and K1) distributions of mammographic examinations with DBT differ from conventional mammography. A field survey of patient volume and x-ray tube usage is important for the shielding design of DBT facilities. The clinical workloads and transmission data presented in this paper may be useful for clinical medical physicists. (C) 2013 American Association of Physicists in Medicine. C1 [Liu, Bob] Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Webster Ctr Adv Res & Educ Radiat, Dept Radiol, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 10 TC 3 Z9 3 U1 0 U2 12 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 JUN PY 2013 VL 40 IS 6 AR 063901 DI 10.1118/1.4803470 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 157IF UT WOS:000319889100040 PM 23718617 ER PT J AU Chang, I Majid, S Saini, S Zaman, MS Yamamura, S Chiyomaru, T Shahryari, V Fukuhara, S Deng, GR Dahiya, R Tanaka, Y AF Chang, Inik Majid, Shahana Saini, Sharanjot Zaman, Mohd S. Yamamura, Soichiro Chiyomaru, Takeshi Shahryari, Varahram Fukuhara, Shinichiro Deng, Guoren Dahiya, Rajvir Tanaka, Yuichiro TI Hrk Mediates 2-Methoxyestradiol- Induced Mitochondrial Apoptotic Signaling in Prostate Cancer Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BH3-ONLY PROTEINS; MEMBRANE PERMEABILIZATION; PROMOTER METHYLATION; BCL-2 PROTEINS; GENE; BAX; INACTIVATION; EXPRESSION; TARGET; IDENTIFICATION AB Prostate cancer is one of the most prevalent cancers in males and ranks as the second most common cause of cancer-related deaths. 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, is a promising anticancer agent for various types of cancers. Although 2-ME has been shown to activate c-Jun-NH2-kinase (JNK) and mitochondrial-dependent apoptotic signaling pathways, the underlying mechanisms, including downstream effectors, remain unclear. Here, we report that the human Bcl-2 homology 3 (BH3)-only protein harakiri (Hrk) is a critical effector of 2-ME-induced JNK/mitochondria-dependent apoptosis in prostate cancer cells. Hrk mRNA and protein are preferentially upregulated by 2-ME, and Hrk induction is dependent on the JNK activation of c-Jun. Hrk knockdown prevents 2-ME-mediated apoptosis by attenuating the decrease in mitochondrial membrane potential, subsequent cytochrome c (cyt c) release, and caspase activation. Involvement of the proapoptotic protein Bak in this process suggested the possible interaction between Hrk and Bak. Thus, Hrk activation by 2-ME or its overexpression displaced Bak from the complex with antiapoptotic protein Bcl-xL, whereas deletion of the Hrk BH3 domain abolished its interaction with Bcl-xL, reducing the proapoptotic function of Hrk. Finally, Hrk is also involved in the 2-ME-mediated reduction of X-linked inhibitor of apoptosis through Bak activation in prostate cancer cells. Together, our findings suggest that induction of the BH3-only protein Hrk is a critical step in 2-ME activation of the JNK-induced apoptotic pathway, targeting mitochondria by liberating proapoptotic protein Bak. (C) 2013 AACR. C1 [Tanaka, Yuichiro] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA. [Tanaka, Yuichiro] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Tanaka, Y (reprint author), San Francisco VA Med Ctr, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA. EM yuichiro.tanaka@ucsf.edu FU Veterans Affairs Merit Review grant; Research Enhancement Award Program FX This study was supported by the Veterans Affairs Merit Review grant and Research Enhancement Award Program (Y. Tanaka). NR 39 TC 6 Z9 7 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 JUN PY 2013 VL 12 IS 6 BP 1049 EP 1059 DI 10.1158/1535-7163.MCT-12-1187 PG 11 WC Oncology SC Oncology GA 160HT UT WOS:000320110500020 PM 23580416 ER PT J AU Hu, J Locasale, JW Bielas, JH O'Sullivan, J Sheahan, K Cantley, LC Vander Heiden, MG Vitkup, D AF Hu, Jie Locasale, Jason W. Bielas, Jason H. O'Sullivan, Jacintha Sheahan, Kieran Cantley, Lewis C. Vander Heiden, Matthew G. Vitkup, Dennis TI Heterogeneity of tumor-induced gene expression changes in the human metabolic network SO NATURE BIOTECHNOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GLUTAMINE-METABOLISM; CANCER METABOLISM; PYRUVATE-KINASE; CELL-METABOLISM; HYPOXIA; GROWTH; HYDROXYLASES; LIPOGENESIS; INHIBITION AB Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., upregulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation) are very heterogeneous. Our analysis also suggests that the expression changes of some metabolic genes (e.g., isocitrate dehydrogenase and fumarate hydratase) may enhance or mimic the effects of recurrent mutations in tumors. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy. C1 [Hu, Jie; Vitkup, Dennis] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10027 USA. [Hu, Jie; Vitkup, Dennis] Columbia Univ, Initiat Syst Biol, New York, NY USA. [Locasale, Jason W.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Bielas, Jason H.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Translat Res Program, Seattle, WA 98104 USA. [Bielas, Jason H.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [O'Sullivan, Jacintha; Sheahan, Kieran] St Vincents Univ Hosp, Dublin 4, Ireland. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Cantley, Lewis C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Sch Med, Boston, MA 02215 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vitkup, Dennis] Columbia Univ, Dept Biomed Informat, New York, NY USA. RP Vitkup, D (reprint author), Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10027 USA. EM dv2121@columbia.edu RI Cantley, Lewis/D-1800-2014; Hu, Jie/J-5075-2012; OI Cantley, Lewis/0000-0002-1298-7653; O'Sullivan, Jacintha/0000-0001-8622-9858; Locasale, Jason/0000-0002-7766-3502 FU US National Institutes of Health [GM079759]; US National Centers for Biomedical Computing [U54CA121852]; NIH Pathway to Independence Award [R00CA168997]; Ellison Medical Foundation New Scholar [AG-NS-0577-09]; National Institute of Environmental Health Sciences [R01ES019319]; New Development Funds from the Fred Hutchinson Cancer Research Center; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; National Cancer Institute FX We would like to sincerely thank the members of the Vitkup laboratory for discussions. This work was supported by US National Institutes of Health grant GM079759 to D.V. and US National Centers for Biomedical Computing grant U54CA121852 to Columbia University. J.W.L. is supported by an NIH Pathway to Independence Award R00CA168997. J.H.B. is supported by an Ellison Medical Foundation New Scholar award AG-NS-0577-09, a National Institute of Environmental Health Sciences grant R01ES019319, and New Development Funds from the Fred Hutchinson Cancer Research Center. M.G.V.H. acknowledges support from the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, the Smith Family and the National Cancer Institute. NR 50 TC 84 Z9 86 U1 0 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2013 VL 31 IS 6 BP 522 EP U11 DI 10.1038/nbt.2530 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 160IO UT WOS:000320113200023 PM 23604282 ER PT J AU Allareddy, V Karimbux, NY Dodson, TB Lee, MK AF Allareddy, Veerasathpurush Karimbux, Nadeem Y. Dodson, Thomas B. Lee, Min Kyeong TI Predictors of never events in patients undergoing radical dissection of cervical lymph nodes SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID SMALL-AREA VARIATIONS; RISK ADJUSTMENT; ADVERSE EVENTS; HEALTH-CARE; COMPLICATIONS; HOSPITALIZATION; MORTALITY; QUALITY; RATES AB Objective. The aim of this study was to identify variables associated with infection-related never events in patients undergoing radical neck dissections for head and neck cancer. Study Design. All hospitalizations with head and neck cancer that underwent radical dissection of cervical lymph nodes were selected from the Nationwide Inpatient Sample. Predictor variables included patient and hospital-level factors. Outcome variable was occurrence of >= 1 never events. Association between predictor and outcome variables was examined by using bivariate and multivariable logistic regression models. Results. There were 10,660 hospitalizations. At least 1 never event occurred in 7.8% of hospitalizations. Teaching hospitals were associated with higher odds of having >= 1 never event compared with nonteaching hospitals (odds ratio 1.92; P = .02). Presence of comorbid conditions and race were other significant predictors of never events. Conclusions. Teaching hospitals and presence of comorbid conditions were associated with higher odds of experiencing a never event. C1 [Allareddy, Veerasathpurush; Lee, Min Kyeong] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Karimbux, Nadeem Y.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Outcomes, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Lee, MK (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM minkyeong_lee@hsdm.harvard.edu NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD JUN PY 2013 VL 115 IS 6 BP 710 EP 716 DI 10.1016/j.oooo.2012.09.004 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 163WN UT WOS:000320368600012 PM 23246228 ER PT J AU Festa, F Rollins, SM Vattem, K Hathaway, M Lorenz, P Mendoza, EA Yu, XB Qiu, J Kilmer, G Jensen, P Webb, B Ryan, ET LaBaer, J AF Festa, Fernanda Rollins, Sean M. Vattem, Krishna Hathaway, Margarita Lorenz, Phillip Mendoza, Eliseo A. Yu, Xiaobo Qiu, Ji Kilmer, Greg Jensen, Penny Webb, Brian Ryan, Ed T. LaBaer, Joshua TI Robust microarray production of freshly expressed proteins in a human milieu SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Human Coupled IVT; In vitro transcription and translation; NAPPA; Protein microarray ID HUMORAL IMMUNE-RESPONSES; RHEUMATOID-ARTHRITIS; CANCER; AUTOANTIBODIES; GENERATION; PROTEOME; ARRAYS; DNA AB Purpose In vitro transcription/translation (IVTT) systems are widely used in proteomics. For clinical applications, mammalian systems are preferred for protein folding and activity; however, the level of protein obtained is low. A new system extracted from human cells (1-Step Human Coupled IVT (HCIVT)) has the potential to overcome this problem and deliver high yields of protein expressed in a human milieu. Experimental design Western blots and self-assembled protein microarrays were used to test the efficiency of protein synthesis by HCIVT compared to rabbit reticulocyte lysate (RRL). The arrays were also used to measure the immune response obtained from serum of patients exposed to pathogens or vaccine. Results HCIVT performed better than RRL in all experiments. The yield of protein synthesized in HCIVT is more than ten times higher than RRL, in both Western blot and protein microarrays. Moreover, HCIVT showed a robust lot-to-lot reproducibility. In immune assays, the signals of many antigens were detected only in HCIVT-expressed arrays, mainly due to the reduction in the background signal and the increased levels of protein on the array. Conclusion and clinical relevance HCIVT is a robust in vitro transcription and translation system that yields high levels of protein produced in a human milieu. It can be used in applications where protein expression in a mammalian system and high yields are needed. The increased immunogenic response of HCIVT-expressed proteins will be critical for biomarker discovery in many diseases, including cancer. C1 [Festa, Fernanda; Hathaway, Margarita; Lorenz, Phillip; Mendoza, Eliseo A.; Yu, Xiaobo; Qiu, Ji; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ 85287 USA. [Rollins, Sean M.; Ryan, Ed T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rollins, Sean M.] Fitchburg State Univ, Fitchburg, MA USA. RP LaBaer, J (reprint author), Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, 1001 S McAllister Ave, Tempe, AZ 85287 USA. EM jlabaer@asu.edu RI Yu, Xiaobo/F-5997-2015 OI Rollins, Sean/0000-0002-3724-1989; FU NIH [U01CA117374, U01AI077883]; Virginia G. Piper Foundation FX The authors would like to thank Garrick Wallstrom for his help in the data analysis and Deborah Paterick for the preparation of the NAPPA schematic figure. This project was supported by the NIH grant U01CA117374, U01AI077883, and Virginia G. Piper Foundation. NR 33 TC 16 Z9 16 U1 0 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1862-8346 EI 1862-8354 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD JUN PY 2013 VL 7 IS 5-6 SI SI BP 372 EP 377 DI 10.1002/prca.201200063 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 166KZ UT WOS:000320554800007 PM 23027544 ER PT J AU Gu, JW Xu, XG Caracappa, PF Liu, B AF Gu, Jianwei Xu, X. George Caracappa, Peter F. Liu, Bob TI Fetal doses to pregnant patients from CT with tube current modulation calculated using Monte Carlo simulations and realistic phantoms SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID MULTIDETECTOR CT; REDUCTION; ORGAN; FETUS; MDCT; DOSIMETRY; SCANNER AB To investigate the radiation dose to the fetus using retrospective tube current modulation (TCM) data selected from archived clinical records. This paper describes the calculation of fetal doses using retrospective TCM data and Monte Carlo (MC) simulations. Three TCM schemes were adopted for use with three pregnant patient phantoms. MC simulations were used to model CT scanners, TCM schemes and pregnant patients. Comparisons between organ doses from TCM schemes and those from non-TCM schemes show that these three TCM schemes reduced fetal doses by 14, 18 and 25 , respectively. These organ doses were also compared with those from ImPACT calculation. It is found that the difference between the calculated fetal dose and the ImPACT reported dose is as high as 46 . This work demonstrates methods to study organ doses from various TCM protocols and potential ways to improve the accuracy of CT dose calculation for pregnant patients. C1 [Gu, Jianwei; Xu, X. George; Caracappa, Peter F.] Rensselaer Polytech Inst, Program Nucl Engn & Engn Phys, Troy, NY 12180 USA. [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Xu, XG (reprint author), Rensselaer Polytech Inst, Program Nucl Engn & Engn Phys, Troy, NY 12180 USA. EM xug2@rpi.edu FU National Cancer Institute [R01CA116743] FX Dr Xinhua Li from Massachusetts General Hospital provided help in CTDI measurements. The CT scanner modelling and MC computing resources were made available from a project funded by the National Cancer Institute (R01CA116743). NR 26 TC 7 Z9 8 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JUN PY 2013 VL 155 IS 1 BP 64 EP 72 DI 10.1093/rpd/ncs312 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 162OO UT WOS:000320274900008 PM 23222824 ER PT J AU Davidson, CL Babson, KA Bonn-Miller, MO Souter, T Vannoy, S AF Davidson, Collin L. Babson, Kimberly A. Bonn-Miller, Marcel O. Souter, Tasha Vannoy, Steven TI The Impact of Exercise on Suicide Risk: Examining Pathways through Depression, PTSD, and Sleep in an Inpatient Sample of Veterans SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; LATE-LIFE DEPRESSION; PHYSICAL-ACTIVITY; PRIMARY-CARE; MENTAL-HEALTH; MAJOR DEPRESSION; COMMUNITY SAMPLE; OLDER-ADULTS AB Suicide has a large public health impact. Although effective interventions exist, the many people at risk for suicide cannot access these interventions. Exercise interventions hold promise in terms of reducing suicide because of their ease of implementation. While exercise reduces depression, and reductions in depressive symptoms are linked to reduced suicidal ideation, no studies have directly linked exercise and suicide risk. The current study examined this association, including potential mediators (i.e., sleep disturbance, posttraumatic stress symptoms, and depression), in a sample of Veterans. SEM analyses revealed that exercise was directly and indirectly associated with suicide risk. Additionally, exercise was associated with fewer depressive symptoms and better sleep patterns, each of which was, in turn, related to lower suicide risk. C1 [Davidson, Collin L.] Denver VA Med Ctr, VA VISN MIRECC 19, Denver, CO USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Babson, Kimberly A.; Souter, Tasha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VAMC, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Souter, Tasha] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Vannoy, Steven] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Davidson, CL (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM collin.davidson@va.gov OI Babson, Kimberly/0000-0002-9233-8230; Vannoy, Steven/0000-0003-3029-8306 NR 73 TC 14 Z9 14 U1 8 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD JUN PY 2013 VL 43 IS 3 BP 279 EP 289 DI 10.1111/sltb.12014 PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 161GO UT WOS:000320180700005 PM 23901428 ER PT J AU Dai, HB Yu, ZY Fan, X Liu, N Yan, M Chen, Z Lo, EH Hajjar, KA Wang, XY AF Dai, Haibin Yu, Zhanyang Fan, Xiang Liu, Ning Yan, Min Chen, Zhong Lo, Eng H. Hajjar, Katherine A. Wang, Xiaoying TI Dysfunction of annexin A2 contributes to hyperglycaemia-induced loss of human endothelial cell surface fibrinolytic activity SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Annexin A2; hyperglycaemia; fibrinolytic activity; advanced glycation end-product; human brain microvascular endothelial cells ID TISSUE-PLASMINOGEN-ACTIVATOR; GLYCATION END-PRODUCTS; CAROTID-ARTERY; POTENTIAL ROLE; IN-VITRO; T-PA; RECEPTOR; ATHEROSCLEROSIS; INHIBITOR-1; THROMBOSIS AB Hyperglycaemia impairs fibrinolytic activity on the surface of endothelial cells, but the underlying mechanisms are not fully understood. In this study, we tested the hypothesis that hyperglycaemia causes dysfunction of the endothelial membrane protein annexin A2, thereby leading to an overall reduction of fibrinolytic activity. Hyperglycaemia for 7 days significantly reduced cell surface fibrinolytic activity in human brain microvascular endothelial cells (HBMEC). Hyperglycaemia also decreased tissue type plasminogen activator (t-PA), plasminogen, and annexin A2 mRNA and protein expression, while increasing plasminogen activator inhibitor-1 (PAI-1). No changes in p11 mRNA or protein expression were detected. Hyperglycaemia significantly increased AGE-modified forms of total cellular and membrane annexin A2. The hyperglycemia-associated reduction in fibrinolytic activity was fully restored upon incubation with recombinant annexin A2 (rA2), but not AGE-modified annexin A2 or exogenous t-PA. Hyperglycaemia decreased t-PA, upregulated PAI-1 and induced AGE-related disruption of annexin A2 function, all of which contributed to the overall reduction in endothelial cell surface fibrinolytic activity. Further investigations to elucidate the underlying molecular mechanisms and pathophysiological implications of A2 derivatisation might ultimately lead to a better understanding of mechanisms of impaired vascular fibrinolysis, and to development of new interventional strategies for the thrombotic vascular complications in diabetes. C1 [Dai, Haibin; Yan, Min; Chen, Zhong] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China. [Dai, Haibin; Yu, Zhanyang; Fan, Xiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. [Dai, Haibin; Yu, Zhanyang; Fan, Xiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Dai, Haibin; Yu, Zhanyang; Fan, Xiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. [Hajjar, Katherine A.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA. RP Dai, HB (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China. EM haibindai@zju.edu.cn; wangxi@helix.mgh.harvard.edu OI Dai, Haibin/0000-0002-5768-2714 FU National Institute of Health [R01-NS065998, UO1-NS072324, P01-NS55104, R01-HL042493, R01-HL090895]; China National Natural Science Foundation [81173040] FX This work was supported in part by the National Institute of Health grants R01-NS065998 and UO1-NS072324 (to X. Wang), P01-NS55104 (to E.H. Lo), and R01-HL042493 and R01-HL090895 (to K.A. Hajjar); and the China National Natural Science Foundation grant 81173040 (to H. Dai). NR 41 TC 11 Z9 12 U1 1 U2 7 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 2013 VL 109 IS 6 BP 1070 EP 1078 DI 10.1160/TH12-12-0944 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 163RY UT WOS:000320355800012 PM 23572070 ER PT J AU Gao, CY Xie, R Li, W Zhou, J Liu, SC Cao, FL Liu, Y Ma, RS Si, Y Liu, Y Bi, YY Gilbert, GE Shi, JL AF Gao, Chunyan Xie, Rui Li, Wen Zhou, Jin Liu, Shuchuan Cao, Fenglin Liu, Yue Ma, Ruishuang Si, Yu Liu, Yan Bi, Yayan Gilbert, Gary E. Shi, Jialan TI Endothelial cell phagocytosis of senescent neutrophils decreases procoagulant activity SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Phagocytosis; endothelial cell; neutrophil; procoagulant activity; lactadherin ID ACUTE PROMYELOCYTIC LEUKEMIA; PHOSPHATIDYL-L-SERINE; APOPTOTIC CELLS; TISSUE FACTOR; BACTERIAL LIPOPOLYSACCHARIDE; DEPENDENT PHAGOCYTOSIS; EXTRACELLULAR TRAPS; BLOOD-COAGULATION; KUPFFER CELLS; WHOLE-BLOOD AB Abundant senescent neutrophils traverse the vascular compartment and may contribute to pathologic conditions. For example, they become procoagulant when undergoing apoptosis and may contribute to thrombosis or inflammation. Our previous studies demonstrated a dominant clearance pathway in which the neutrophils can be phagocytosed by liver macrophages. The aim of this study was to explore an alternate pathway of neutrophil clearance by endothelial cells. Phagocytosis of the neutrophils by endothelial cells was performed using various experimental approaches including flow cytometry, confocal microscopy and electron microscopy assays in vitro and in vivo. Procoagulant activity of cultured neutrophils was evaluated by coagulation time, factor Xase and prothrombinase assays. Lactadherin functioned as a novel probe for the detection of phosphatidylserine on apoptotic cells, an opsonin (bridge) between apoptotic cell and phagocyte for promoting phagocytosis, and an efficient anticoagulant for inhibition of factor Xase and thrombin formation. When cultured, purified human neutrophils spontaneously entered apoptosis and developed, procoagulant activity that was directly related to the degree of phosphatidylserine exposure. Co-culture of aged neutrophils and endothelial cells resulted in phagocytosis of the neutrophils and prolonged coagulation time. Lactadherin diminished the procoagulant activity and increased the rate of neutrophil clearance. In vivo, neutrophils were sequestered by endothelial cells after blockade of Kupffer cells, a process that was dependent upon both phosphatidylserine exposure and P-selectin expression. Thus, the ability of endothelial cells to clear senescent neutrophils may limit the procoagulant and/or inflammatory impact of these cells. C1 [Gao, Chunyan; Xie, Rui; Li, Wen; Zhou, Jin; Liu, Shuchuan; Cao, Fenglin; Liu, Yue; Ma, Ruishuang; Si, Yu; Liu, Yan; Shi, Jialan] Heilongjiang Inst Hematol & Oncol, Dept Hematol, Harbin, Peoples R China. [Bi, Yayan] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin 150001, Peoples R China. [Gilbert, Gary E.; Shi, Jialan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Shi, JL (reprint author), Harbin Med Univ, Affiliated Hosp 1, Dept Med, 23 Youzheng St, Harbin 150001, Peoples R China. EM jialan_shi@hms.harvard.edu FU National Natural Science Foundation of China [30871227, 81270588]; Science Foundation of Heilongjiang Province [GB08C401-02] FX This work was supported by grants from the National Natural Science Foundation of China (30871227 and 81270588), and the Science Foundation of Heilongjiang Province (GB08C401-02). NR 49 TC 8 Z9 8 U1 2 U2 10 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 2013 VL 109 IS 6 BP 1079 EP 1090 DI 10.1160/TH12-12-0894 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 163RY UT WOS:000320355800013 PM 23571768 ER PT J AU Dzik, WS Cserti-Gazdewich, CM Stowell, C AF Dzik, Walter Sunny Cserti-Gazdewich, Christine M. Stowell, Christopher TI Tissue hypoxia results in lactic acidosis SO TRANSFUSION LA English DT Article C1 [Dzik, Walter Sunny; Cserti-Gazdewich, Christine M.; Stowell, Christopher] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 3 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2013 VL 53 IS 6 BP 1168 EP 1168 DI 10.1111/j.1537-2995.2012.03926.x PG 1 WC Hematology SC Hematology GA 161HI UT WOS:000320183000005 PM 23750930 ER PT J AU Saxena, R Welt, CK AF Saxena, R. Welt, C. K. TI Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes SO ACTA DIABETOLOGICA LA English DT Article DE Testosterone; FSH; Hyperandrogenism; Triglycerides ID GENOME-WIDE ASSOCIATION; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; SUSCEPTIBILITY LOCI; SYNDROME PCOS; COMMON VARIANTS; FAMILY-HISTORY; ADMIXTURE MAP; TCF7L2 GENE; FTO GENE AB Polycystic ovary syndrome (PCOS) is a disorder of irregular menses, hyperandrogenism and/or polycystic ovary morphology. A large proportion of women with PCOS also exhibit insulin resistance, beta-cell dysfunction, impaired glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that genetic variants that predispose to risk of T2D also result in risk of PCOS. Variants robustly associated with T2D in candidate gene or genome-wide association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years. Metabolic, reproductive and anthropomorphic data were examined as a function of the T2D variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. There was a nominal association between variants in KCNJ11 and risk of PCOS. However, a risk score of 33 independent T2D-associated variants from GWAS was not significantly associated with PCOS. T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes risk variants are not important risk variants for PCOS. C1 [Saxena, R.] Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA. [Saxena, R.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Welt, C. K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU National Institutes of Health [U01 HD 4417, 1R01HD065029]; ADA [1-10-CT-57]; National Center for Research Resources [M01-RR-01066]; Harvard Clinical and Translational Science Center [1 UL1 RR025758] FX This work was supported by the National Institutes of Health U01 HD 4417 and 1R01HD065029, ADA 1-10-CT-57, and 1 UL1 RR025758 Harvard Clinical and Translational Science Center and M01-RR-01066 from the National Center for Research Resources. NR 46 TC 8 Z9 8 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD JUN PY 2013 VL 50 IS 3 BP 451 EP 457 DI 10.1007/s00592-012-0383-4 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 159SP UT WOS:000320066500021 PM 22389004 ER PT J AU Serrano-Pozo, A Gomez-Isla, T Growdon, JH Frosch, MP Hyman, BT AF Serrano-Pozo, Alberto Gomez-Isla, Teresa Growdon, John H. Frosch, Matthew P. Hyman, Bradley T. TI A Phenotypic Change But Not Proliferation Underlies Glial Responses in Alzheimer Disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; POSITRON-EMISSION-TOMOGRAPHY; PROTEIN TRANSGENIC MICE; MICROGLIAL CELLS; MOUSE MODEL; NEUROFIBRILLARY TANGLES; AMYLOID DEPOSITION; SENILE DEMENTIA; APOE GENOTYPE; NEURON LOSS AB Classical immunohistochemical studies in the Alzheimer disease (AD) brain reveal prominent glial reactions, but whether this pathological feature is due primarily to cell proliferation or to a phenotypic change of existing resting cells remains controversial. We performed double-fluorescence immunohistochemical studies of astrocytes and microglia, followed by unbiased stereology-based quantitation in temporal cortex of 40 AD patients and 32 age-matched nondemented subjects. Glial fibrillary acidic protein (GFAP) and major histocompatibility complex II (MHC2) were used as markers of astrocytic and microglial activation, respectively. Aldehyde dehydrogenase 1 L1 and glutamine synthetase were used as constitutive astrocytic markers, and ionized calcium-binding adaptor molecule 1 (IBA1) as a constitutive microglial marker. As expected, AD patients had higher numbers of GFAP(+) astrocytes and MHC2(+) microglia than the nondemented subjects. However, both groups had similar numbers of total astrocytes and microglia and, in the AD group, these total numbers remained essentially constant over the clinical course of the disease. The GFAP immunoreactivity of astrocytes, but not the MHC2 immunoreactivity of microglia, increased in parallel with the duration of the clinical illness in the AD group. Cortical atrophy contributed to the perception of increased glia density. We conclude that a phenotypic change of existing glial cells, rather than a marked proliferation of glial precursors, accounts for the majority of the glial responses observed in the AD brain. C1 [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab, Dept Pathol, Boston, MA 02114 USA. [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hyman, BT (reprint author), MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, 16th St,Bldg 114, Charlestown, MA 02129 USA. EM bhyman@partners.org OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU NIH [AG08487, P50-AG05134]; Fundacion Alfonso Martin Escudero (Madrid, Spain) FX Supported by NIH grants AG08487 and P50-AG05134 (to B.T.H.). A.S.-P. was awarded a fellowship from Fundacion Alfonso Martin Escudero (Madrid, Spain). NR 64 TC 20 Z9 20 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2013 VL 182 IS 6 BP 2332 EP 2344 DI 10.1016/j.ajpath.2013.02.031 PG 13 WC Pathology SC Pathology GA 155WT UT WOS:000319781800036 PM 23602650 ER PT J AU He, LZ Marneros, AG AF He, Lizhi Marneros, Alexander G. TI Macrophages Are Essential for the Early Wound Healing Response and the Formation of a Fibrovascular Scar SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULARIZATION; VASCULAR ENDOTHELIUM; MACULAR DEGENERATION; MICE; EXPRESSION; CELLS; PROGENITORS; DEPLETION AB After wounding, multiple cell types interact to form a fibrovascular scar; the formation and cellular origins of these scars are incompletely understood. We used a laser-injury wound model of choroidal neovascularization in the eye to determine the spatiotemporal cellular events that Lead to formation of a fibrovascular scar. After Laser injury, F4/80(+) myeloid cells infiltrate the wound site and induce smooth muscle actin (SMA) expression in adjacent retinal pigment epithelial cells, with subsequent formation of a SMA(+)NG2(+) myofibroblastic scaffold, into which endothelial cells then infiltrate to form a fibrovascular Lesion. Cells of the fibrovascular scaffold express the proangiogenic factor IL-1 beta strongly, whereas retinal pigment epithelial cells are the main source of VEGF-A. Subsequent choroidal neovascularization is limited to the area demarcated by this myofibroblastic scaffold and occurs independently of epithelial- or myeloid-derived VEGF-A. The SMA(+)NG2(+) myofibroblastic cells, F4/80(+) macrophages, and adjacent epithelial cells actively proliferate in the early phase of the wound healing response. Cell-lineage tracing experiments suggest that the SMA(+)NG2(+) myofibroblastic scaffold originates from choroidal pericyte-like cells. Targeted ablation of macrophages inhibits the formation of this fibrovascular scaffold, and expression analysis reveals that these macrophages are Arg1(+)YM1(+)F4/80(+) alternatively activated M2-Like macrophages, which do not require IL-4/STAT6 or IL-10 signaling for their activation. Thus, macrophages are essential for the early wound healing response and the formation of a fibrovascular scar. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA. RP Marneros, AG (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Bldg 149,13th St Rm 3-216, Charlestown, MA 02129 USA. EM amarneros@partners.org FU NIH-NEI [R01-EY019297] FX Supported by NIH-NEI grant R01-EY019297 (A.G.M.). NR 32 TC 27 Z9 32 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2013 VL 182 IS 6 BP 2407 EP 2417 DI 10.1016/j.ajpath.2013.02.032 PG 11 WC Pathology SC Pathology GA 155WT UT WOS:000319781800042 PM 23602833 ER PT J AU Shi, YX Lo, CS Chenier, I Maachi, H Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Shi, Yixuan Lo, Chao-Sheng Chenier, Isabelle Maachi, Hasna Filep, Janos G. Ingelfinger, Julie R. Zhang, Shao-Ling Chan, John S. D. TI Overexpression of catalase prevents hypertension and tubulointerstitial fibrosis and normalization of renal angiotensin-converting enzyme-2 expression in Akita mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE catalase; hypertension; angiotensin-converting enzyme-2; tubulointerstitial fibrosis ID PROXIMAL TUBULAR CELLS; DIABETIC KIDNEY-DISEASE; TRANSGENIC MICE; OXIDATIVE STRESS; GENE-EXPRESSION; BLOOD-PRESSURE; APOPTOSIS; ACE2; CARBOXYPEPTIDASE; NEPHROPATHY AB We investigated the relationship among oxidative stress, hypertension, renal injury, and angiotensin-converting enzyme-2 (ACE2) expression in type 1 diabetic Akita mice. Blood glucose, blood pressure, and albuminuria were monitored for up to 5 mo in adult male Akita and Akita catalase (Cat) transgenic (Tg) mice specifically overexpressing Cat, a key antioxidant enzyme in their renal proximal tubular cells (RPTCs). Same-age non-Akita littermates and Cat-Tg mice served as controls. In separate studies, adult male Akita mice (14 wk) were treated with ANG 1-7 (500 mu g.kg(-1).day(-1) sc) +/- A-779, an antagonist of the Mas receptor (10 mg.kg(-1).day(-1) sc), and euthanized at the age of 18 wk. The left kidneys were processed for histology and apoptosis studies. Renal proximal tubules were isolated from the right kidneys to assess protein and gene expression. Urinary angiotensinogen (AGT), angiotensin II (ANG II), and ANG 1-7 were quantified by specific ELISAs. Overexpression of Cat attenuated renal oxidative stress; prevented hypertension; normalized RPTC ACE2 expression and urinary ANG 1-7 levels (both were low in Akita mice); ameliorated glomerular filtration rate, albuminuria, kidney hypertrophy, tubulointerstitial fibrosis, and tubular apoptosis; and suppressed profibrotic and proapoptotic gene expression in RPTCs of Akita Cat-Tg mice compared with Akita mice. Furthermore, daily administration of ANG 1-7 normalized systemic hypertension in Akita mice, which was reversed by A-779. These data demonstrate that Cat overexpression prevents hypertension and progression of nephropathy and highlight the importance of intrarenal oxidative stress and ACE2 expression contributing to hypertension and renal injury in diabetes. C1 [Shi, Yixuan; Lo, Chao-Sheng; Chenier, Isabelle; Maachi, Hasna; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, Ctr Hosp Univ Montreal CRCHUM, Hotel Dieu Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada. [Filep, Janos G.] Univ Montreal, Maisonneuve Rosemont Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, Ctr Hosp Univ Montreal CRCHUM, Hotel Dieu Hosp, Ctr Rech, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU Kidney Foundation of Canada; Canadian Institutes of Health Research [MOP-84363, MOP-93650, MOP-106688, MOP-86450, MOP-12573]; National Heart, Lung, and Blood Institute Grant [HL-48455]; Foundation of the CHUM FX This work was supported in part by grants from the Kidney Foundation of Canada (to J. S. Chan); Canadian Institutes of Health Research Grants MOP-84363, MOP-93650, and MOP-106688 (to J. S. Chan), MOP-86450 (to S. L. Zhang), and MOP-12573 (to J. G. Filep); National Heart, Lung, and Blood Institute Grant HL-48455 (to J. R. Ingelfinger); and Foundation of the CHUM. NR 49 TC 9 Z9 9 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2013 VL 304 IS 11 BP F1335 EP F1346 DI 10.1152/ajprenal.00405.2012 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 156GQ UT WOS:000319810300003 PM 23552863 ER PT J AU Borzecki, AM Cevasco, M Mull, H Shin, M Itani, K Rosen, AK AF Borzecki, Ann M. Cevasco, Marisa Mull, Hillary Shin, Marlena Itani, Kamal Rosen, Amy K. TI Improving the identification of Postoperative Wound Dehiscence missed by the Patient Safety Indicator algorithm SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Postoperative wound dehiscence; Adverse events; Quality of care; Patient safety; Quality indicators AB BACKGROUND: The Patient Safety Indicator (PSI) Postoperative Wound Dehiscence (PWD) is an administrative data-based algorithm that flags cases using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 54.61 (abdominal wall disruption reclosure). We examined how often PWD missed events and explored ways to improve event identification. METHODS: We selected 125 high-risk unflagged cases based on predicted probability and the presence of clinically relevant codes. We determined the false-negative proportion and associated reasons through chart review and calculated likelihood ratios of associated codes. RESULTS: Thirty-two percent of cases were false negatives, 60% of which lacked any abdominal wall repair codes. All individual codes had low likelihood ratios; the combination of diagnosis code 998.3x (operative wound disruption) and particular abdominal wall repair procedure codes occurred exclusively in false-negative cases (representing 24% of false-negative cases). CONCLUSIONS: Among high-risk cases, the PWD algorithm frequently missed events. Coder training to clarify assignment of abdominal wall repair codes, plus adding specific code combinations to the algorithm, would improve event identification. Published by Elsevier Inc. C1 [Borzecki, Ann M.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Borzecki, Ann M.; Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Cevasco, Marisa; Itani, Kamal] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Cevasco, Marisa] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Mull, Hillary; Shin, Marlena; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Mull, Hillary; Itani, Kamal; Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Itani, Kamal] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Borzecki, AM (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. EM amb@bu.edu FU US Department of Veterans Affairs Health Services Research and Development Service [SDR 07-002] FX This study was funded by the US Department of Veterans Affairs Health Services Research and Development Service grant number SDR 07-002. The funding agency had no involvement in: study design, data collection, interpretation or analysis, manuscript writing or the decision to submit this work for publication. NR 21 TC 1 Z9 1 U1 1 U2 2 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 JUN PY 2013 VL 205 IS 6 BP 674 EP 680 DI 10.1016/j.amjsurg.2012.07.040 PG 7 WC Surgery SC Surgery GA 156DY UT WOS:000319802500009 PM 23395582 ER PT J AU Lahtinen, AM Havulinna, AS Noseworthy, PA Jula, A Karhunen, PJ Perola, M Newton-Cheh, C Salomaa, V Kontula, K AF Lahtinen, Annukka M. Havulinna, Aki S. Noseworthy, Peter A. Jula, Antti Karhunen, Pekka J. Perola, Markus Newton-Cheh, Christopher Salomaa, Veikko Kontula, Kimmo TI Prevalence of arrhythmia-associated gene mutations and risk of sudden cardiac death in the Finnish population SO ANNALS OF MEDICINE LA English DT Article DE Arrhythmia; genetic epidemiology; genetics; mutation; sudden cardiac death ID LONG-QT SYNDROME; POLYMORPHIC VENTRICULAR-TACHYCARDIA; T-WAVE ALTERNANS; RYANODINE RECEPTOR; FOUNDER MUTATIONS; UNEXPLAINED DEATH; HEART-DISEASE; PLAKOPHILIN-2 MUTATIONS; CARDIOVASCULAR RISK; INTERVAL DURATION AB Background. Sudden cardiac death (SCD) remains a major cause of death in Western countries. It has a heritable component, but previous molecular studies have mainly focused on common genetic variants. We studied the prevalence, clinical phenotypes, and risk of SCD presented by ten rare mutations previously associated with arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, or catecholaminergic polymorphic ventricular tachycardia. Methods. The occurrence of ten arrhythmia-associated mutations was determined in four large prospective population cohorts (FINRISK 1992, 1997, 2002, and Health 2000, n = 28,465) and two series of forensic autopsies (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 825). Follow-up data were collected from national registries. Results. The ten mutations showed a combined prevalence of 79 per 10,000 individuals in Finland, and six of them showed remarkable geographic clustering. Of a total of 715 SCD cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W. Conclusions. Arrhythmia-associated mutations are prevalent in the general Finnish population but do not seem to present a major risk factor for SCD, at least during a mean of 10-year follow-up of a random adult population sample. C1 [Lahtinen, Annukka M.; Kontula, Kimmo] Univ Helsinki, Res Programs Unit, FIN-00290 Helsinki, Finland. [Lahtinen, Annukka M.; Kontula, Kimmo] Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland. [Havulinna, Aki S.; Perola, Markus; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland. [Noseworthy, Peter A.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Noseworthy, Peter A.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Noseworthy, Peter A.; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Jula, Antti] Natl Inst Hlth & Welf, Turku, Finland. [Karhunen, Pekka J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Karhunen, Pekka J.] Tampere Univ Hosp, Ctr Lab Med, Tampere, Finland. [Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland. RP Kontula, K (reprint author), Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland. EM kimmo.kontula@hus.fi OI Tuiskula, Annukka/0000-0002-6538-635X FU Finnish Cultural Foundation; Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology; Burroughs Wellcome Fund travel grant; Finnish Academy SALVE program 'Pubgensense ' [10404]; Wellcome Trust; Academy of Finland [129494, 139635]; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; National Institutes of Health [HL080025, HL098283]; Doris Duke Charitable Foundation; Burroughs Wellcome Fund FX The authors report no conflicts of interest. This study was supported by the Finnish Cultural Foundation (to A. M. L.); the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology (to P.A.N.); a Burroughs Wellcome Fund travel grant (to P.A.N.); Finnish Academy SALVE program 'Pubgensense ' (#10404 to M. P.); the Wellcome Trust, the Academy of Finland (to K. K. and #129494 and #139635 to V. S.); the Finnish Foundation for Cardiovascular Research (to K. K. and V. S.); the Sigrid Juselius Foundation (to K. K. and V. S.); the National Institutes of Health (HL080025, HL098283 to C. N.-C.); the Doris Duke Charitable Foundation (to C. N.-C.); and the Burroughs Wellcome Fund (to C.N.-C.). NR 56 TC 9 Z9 9 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PD JUN PY 2013 VL 45 IS 4 BP 328 EP 335 DI 10.3109/07853890.2013.783995 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 156RZ UT WOS:000319841400004 PM 23651034 ER PT J AU Navarro-Millan, I Charles-Schoeman, C Yang, S Bathon, JM Bridges, SL Chen, L Cofield, SS Dell'Italia, LJ Moreland, LW O'Dell, JR Paulus, HE Curtis, JR AF Navarro-Millan, Iris Charles-Schoeman, Christina Yang, Shuo Bathon, Joan M. Bridges, S. Louis, Jr. Chen, Lang Cofield, Stacey S. Dell'Italia, Louis J. Moreland, Larry W. O'Dell, James R. Paulus, Harold E. Curtis, Jeffrey R. TI Changes in Lipoproteins Associated With Methotrexate or Combination Therapy in Early Rheumatoid Arthritis: Results From the Treatment of Early Rheumatoid Arthritis Trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; HIGH-DENSITY-LIPOPROTEIN; MYOCARDIAL-INFARCTION; LIPID PROFILES; RECEPTOR INHIBITION; DOUBLE-BLIND; ATHEROSCLEROSIS; CHOLESTEROL; TOCILIZUMAB; DISEASE AB Objective To study changes in lipid profiles at 24 weeks among patients with early rheumatoid arthritis (RA) participating in the Treatment of Early RA (TEAR) trial and randomized to receive methotrexate (MTX) plus etanercept, triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or aggressively titrated MTX monotherapy. Methods This TEAR substudy included 459 participants with biologic specimens. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured at 0 and 24 weeks. Results At 24 weeks, there were statistically significant increases in mean cholesterol levels in the MTX plus etanercept, triple therapy, and MTX monotherapy arms. The observed increases were 31.4 mg/dl, 28.7 mg/dl, and 30 mg/dl in LDL cholesterol, 19.3 mg/dl, 22.3 mg/dl, and 20.6 mg/dl in HDL cholesterol, and 56.8 mg/dl, 53 mg/dl, and 57.3 mg/dl in total cholesterol (P < 0.0001 versus baseline for each comparison). There was a statistically significant decrease in the ratio of total cholesterol to HDL cholesterol at 24 weeks in all 3 treatment groups versus baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C-reactive protein, but not the Disease Activity Score in 28 joints, was associated with change in LDL cholesterol (P = 0.03) and total cholesterol (P = 0.01). Baseline glucocorticoid use was associated with changes in HDL cholesterol (P = 0.03) and total cholesterol (P = 0.02). Conclusion Levels of total cholesterol, LDL cholesterol, and HDL cholesterol increased comparably shortly after initiation of MTX plus etanercept, triple therapy, and MTX monotherapy among patients with early RA with active disease participating in a clinical trial. The clinical relevance of short-term changes in traditional lipids on cardiovascular outcomes remains to be determined. C1 [Navarro-Millan, Iris; Yang, Shuo; Bridges, S. Louis, Jr.; Chen, Lang; Cofield, Stacey S.; Dell'Italia, Louis J.; Curtis, Jeffrey R.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Charles-Schoeman, Christina; Paulus, Harold E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Bathon, Joan M.] Columbia Univ, New York, NY USA. [Dell'Italia, Louis J.] Birmingham VA Med Ctr, Birmingham, AL USA. [Moreland, Larry W.] Univ Pittsburgh, Pittsburgh, PA USA. [O'Dell, James R.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Curtis, JR (reprint author), Univ Alabama Birmingham, 510 20th St South,FOT 802D, Birmingham, AL 35294 USA. EM jcurtis@uab.edu FU Arthritis Foundation; NIH (National Heart, Lung, and Blood Institute) [5K23-HL-094834]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [R21-AR-057913-01A1]; Margaret J. Miller Endowed Professor of Arthritis Research Chair at the University of Pittsburgh; NIH [AR-053351, R01-AR-052658]; Agency for Healthcare Research and Quality [R01-HS-018517]; Amgen FX Supported by the Arthritis Foundation (grant to Dr. Curtis). Dr. Charles-Schoeman's work was supported by the NIH (National Heart, Lung, and Blood Institute grant 5K23-HL-094834 and National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R21-AR-057913-01A1). Dr. Moreland's work was supported by the Margaret J. Miller Endowed Professor of Arthritis Research Chair at the University of Pittsburgh. Dr. Curtis' work was supported by the NIH (grant AR-053351) and the Agency for Healthcare Research and Quality (grant R01-HS-018517). The Treatment of Early Rheumatoid Arthritis (TEAR) biorepository was funded by the NIH (grant R01-AR-052658 to Dr. Bridges). The TEAR trial was supported by Amgen. NR 39 TC 38 Z9 40 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2013 VL 65 IS 6 BP 1430 EP 1438 DI 10.1002/art.37916 PG 9 WC Rheumatology SC Rheumatology GA 155IG UT WOS:000319740600004 PM 23460074 ER PT J AU Wofsy, D Hillson, JL Diamond, B AF Wofsy, David Hillson, Jan L. Diamond, Betty TI Comparison of Alternative Primary Outcome Measures for Use in Lupus Nephritis Clinical Trials SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CYCLOPHOSPHAMIDE; THERAPY AB Objective Clinical trials of therapies for lupus nephritis have used many different primary outcome measures, ranging from complete response to time to end-stage renal disease. The objective of this study was to compare several possible outcome measures, using data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which outcome measure, if any, was best able to discern differences among treatment groups. Methods Study patients received either abatacept or placebo, on a background of mycophenolate mofetil and glucocorticoids. Using data from this trial, the following primary outcome measures at 24 and 52 weeks were compared: complete response rate, major clinical response rate, total response rate (complete plus partial response), improvement in proteinuria, improvement in estimated glomerular filtration rate, and frequency of treatment failure. Time to complete response was also evaluated. Results Complete response rate, major clinical response rate, and time to complete response were the measures that best discriminated between the abatacept groups and placebo, and the sensitivities of these 3 measures were comparable. For these measures, sample sizes of 50 patients would have been sufficient to demonstrate a statistically significant difference between treatment and control at 52 weeks. Each of the other measures also discriminated between treatment and control, but much larger group sizes would have been required to determine statistical significance. Conclusion The choice of primary outcome measure can substantially influence the ability to detect therapeutic benefit in lupus nephritis trials. This study suggests that complete response rate, major clinical response rate at 52 weeks, and time to complete response may be the most sensitive outcome measures for detecting differences among therapeutic regimens. C1 [Wofsy, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hillson, Jan L.] Bristol Myers Squibb Co, Princeton, NJ USA. [Diamond, Betty] Feinstein Inst Med Res, Manhasset, NY USA. RP Wofsy, D (reprint author), San Francisco VA Med Ctr, Arthrit Immunol Unit 111R, 4150 Clement St, San Francisco, CA 94121 USA. EM wofsyd@medsch.ucsf.edu FU Rosalind Russell Medical Research Center for Arthritis at the University of California, San Francisco FX Supported by the Rosalind Russell Medical Research Center for Arthritis at the University of California, San Francisco. NR 8 TC 31 Z9 31 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2013 VL 65 IS 6 BP 1586 EP 1591 DI 10.1002/art.37940 PG 6 WC Rheumatology SC Rheumatology GA 155IG UT WOS:000319740600021 PM 23529285 ER PT J AU Vudattu, NK Strle, K Steere, AC Drouin, EE AF Vudattu, Nalini K. Strle, Klemen Steere, Allen C. Drouin, Elise E. TI Dysregulation of CD4+CD25high T Cells in the Synovial Fluid of Patients With Antibiotic-Refractory Lyme Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INDUCED TNF RECEPTOR; BORRELIA-BURGDORFERI; AUTOIMMUNE-DISEASES; CUTTING EDGE; JOINT FLUID; SUPPRESSION; RESPONSES; LIGAND; INFLAMMATION; MOLECULES AB Objective To examine the role of immune dysregulation in antibiotic-refractory Lyme arthritis by comparing the phenotype, frequency, and function of CD4+ Teff cells and Treg cells in patients with antibiotic- responsive arthritis and patients with antibiotic-refractory arthritis. Methods Matched peripheral blood and synovial fluid samples from 15 patients with antibiotic-responsive arthritis were compared with those from 16 patients with antibiotic-refractory arthritis, using flow cytometry, suppression assays, and cytokine assays. Results Critical differences between the 2 patient groups were observed in the synovial fluid CD4+CD25high population, a cell subset usually composed of FoxP3-positive Treg cells. In patients with antibiotic-refractory arthritis, this cell population often had fewer FoxP3-positive cells and a greater frequency of FoxP3-negative (Teff) cells compared with patients with antibiotic-responsive arthritis. Moreover, the expression of glucocorticoid-induced tumor necrosis factor receptor and OX40 on CD4+CD25high cells was significantly higher in the antibody-refractory group. Suppression assays showed that CD4+CD25high cells in patients with antibiotic-refractory arthritis did not effectively suppress proliferation of CD4+CD25- cells or secretion of interferon- and tumor necrosis factor , whereas those cells in patients with antibiotic-responsive arthritis did suppress proliferation of CD4+CD25- cells and secretion of interferon- and tumor necrosis factor . Finally, in the antibiotic-refractory group, higher ratios of CD25high FoxP3-negative cells to CD25high FoxP3-positive cells correlated directly with a longer duration of arthritis after antibiotic treatment. Conclusion Patients with antibiotic-refractory Lyme arthritis often have lower frequencies of Treg cells, higher expression of activation coreceptors, and less effective inhibition of proinflammatory cytokines. This suggests that immune responses in these patients are excessively amplified, leading to immune dysregulation and antibiotic-refractory arthritis. C1 [Vudattu, Nalini K.; Strle, Klemen; Steere, Allen C.; Drouin, Elise E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vudattu, Nalini K.; Strle, Klemen; Steere, Allen C.; Drouin, Elise E.] Harvard Univ, Sch Med, Boston, MA USA. RP Drouin, EE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA. EM edrouin@partners.org RI Vudattu, Nalini/L-1779-2014 OI Vudattu, Nalini/0000-0001-6705-3332 FU NIH [AI-101175, AR-20358]; Mathers Foundation; English, Bonter; Mitchell Foundation; Eshe Fund; Lyme/Arthritis Research Fund at Massachusetts General Hospital; Massachusetts General Hospital; Walter J. and Lille A. Berbecker Foundation; Arthritis Foundation FX Supported by the NIH (grants AI-101175 and AR-20358), the Mathers Foundation, the English, Bonter, Mitchell Foundation, the Eshe Fund, and the Lyme/Arthritis Research Fund at Massachusetts General Hospital. Dr. Vudattu is recipient of a Postdoctoral Fellowship from the Walter J. and Lille A. Berbecker Foundation. Dr. Strle is recipient of Postdoctoral Fellowships from the Walter J. and Lille A. Berbecker Foundation and the Arthritis Foundation. NR 46 TC 13 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JUN PY 2013 VL 65 IS 6 BP 1643 EP 1653 DI 10.1002/art.37910 PG 11 WC Rheumatology SC Rheumatology GA 155IG UT WOS:000319740600027 PM 23450683 ER PT J AU Giralt, S McCarthy, PL Anderson, KC Carter, SL Richardson, PG Rajkumar, SV Laport, GG Stadtmauer, EA Pasquini, MC Horowitz, MM AF Giralt, Sergio McCarthy, Philip L. Anderson, Kenneth C. Carter, Shelly L. Richardson, Paul G. Rajkumar, S. Vincent Laport, Ginna G. Stadtmauer, Edward A. Pasquini, Marcelo C. Horowitz, Mary M. TI Anatomy of a Successful Practice-Changing Study: A Blood and Marrow Transplantation Clinical Trials Network-National Cancer Institute Cooperative Group Collaboration SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; LENALIDOMIDE C1 [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA. [Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. [Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Rajkumar, S. Vincent] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA. [Laport, Ginna G.] Stanford Univ, Ctr Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Myeloma Program, Philadelphia, PA 19104 USA. [Pasquini, Marcelo C.; Horowitz, Mary M.] Med Coll Wisconsin, Div Hematol & Oncol, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Div Hematol & Oncol, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM marymh@mcw.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833 FU NCI NIH HHS [U10 CA021115, U24 CA076518, CA33601, CA31946, U10 CA031946, CA21115, U10 CA033601]; NHLBI NIH HHS [U01 HL069294, U10 HL069294, U10 HL069315, U10 HL069348, U10 HL069286, U10 HL069291, HL069294] NR 5 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2013 VL 19 IS 6 BP 858 EP 859 DI 10.1016/j.bbmt.2013.03.015 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 156TX UT WOS:000319847900005 PM 23545332 ER PT J AU Kim, HT Armand, P AF Kim, Haesook T. Armand, Philippe TI Clinical Endpoints in Allogeneic Hematopoietic Stem Cell Transplantation Studies: The Cost of Freedom SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Allogeneic transplantation; Clinical endpoints; Competing risks data ID BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; UMBILICAL-CORD BLOOD; CONSENSUS DEVELOPMENT PROJECT; TREATMENT-RELATED MORTALITY; ACUTE MYELOID-LEUKEMIA; COMPETING RISKS DATA; WORKING GROUP-REPORT; CUMULATIVE INCIDENCE; UNRELATED DONORS AB When designing a study for allogeneic hematopoietic stem cell transplantation (HSCT), many choices must be made, including conditioning regimen, stem cell source, and graft-versus-host disease (GVHD) prevention method. For each of these, there are a growing number of options, which can be combined into a bewildering number of possible HSCT protocols. To properly interpret the results of a given strategy and compare them with others, it is essential that there be agreement on the definitions and estimation methods of HSCT endpoints. We report a survey of the recent HSCT literature that confirms the heterogeneity of endpoint definitions and estimation methods used. Unfortunately, this heterogeneity may lead to significant biases in the estimates of key endpoints, including nonrelapse mortality, relapse, GVHD, or engraftment. This can preclude adequate comparisons among studies, even though such comparisons are the major tool with which to improve HSCT outcome. In the context of our survey, we discuss some of the statistical issues that arise when dealing with HSCT endpoints and the ramifications of the choice of endpoint definition, when the endpoint occurs in the context of competing risks. Our hope is to generate discussion and motivate a search for consensus among those who perform transplantations and statisticians. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 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 NIAID [U19 AI29530]; NCI [PO1 CA142106]; American Society of Hematology; ASCO/Conquer Cancer Foundation FX Supported by NIAID U19 AI29530, and NCI PO1 CA142106. P.A. is a recipient of an American Society of Hematology Scholar Award and an ASCO/Conquer Cancer Foundation Career Development Award. NR 32 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2013 VL 19 IS 6 BP 860 EP 866 DI 10.1016/j.bbmt.2013.01.003 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 156TX UT WOS:000319847900006 PM 23305679 ER PT J AU Hitzler, JK He, WS Doyle, J Cairo, M Camitta, BM Chan, KW Perez, MAD Fraser, C Gross, TG Horan, JT Kennedy-Nasser, AA Kitko, C Kurtzberg, J Lehmann, L O'Brien, T Pulsipher, MA Smith, FO Zhang, MJ Eapen, M Carpenter, PA AF Hitzler, Johann K. He, Wensheng Doyle, John Cairo, Mitchell Camitta, Bruce M. Chan, Ka Wah Perez, Miguel A. Diaz Fraser, Christopher Gross, Thomas G. Horan, John T. Kennedy-Nasser, Alana A. Kitko, Carrie Kurtzberg, Joanne Lehmann, Leslie O'Brien, Tracey Pulsipher, Michael A. Smith, Franklin O. Zhang, Mei-Jie Eapen, Mary Carpenter, Paul A. CA CIBMTR Pediat Canc Working Comm TI Outcome of Transplantation for Acute Myelogenous Leukemia in Children with Down Syndrome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic stem cell transplantation; Down syndrome; Trisomy 21; AML; ALL; Relapse; Pediatric ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ONCOLOGY GROUP; THERAPY; TOXICITY; DISEASE; REGIMEN; TRIAL; RISK AB Data on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P<.001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P=.04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML Overall mortality risk (HR, 2.86; P<.001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Hitzler, Johann K.; Doyle, John] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [He, Wensheng; Zhang, Mei-Jie; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Cairo, Mitchell] New York Med Coll, Valhalla, NY 10595 USA. [Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Chan, Ka Wah] Texas Transplant Inst, San Antonio, TX USA. [Perez, Miguel A. Diaz] Hosp Nino Jesus, Madrid, Spain. [Fraser, Christopher] Royal Childrens Hosp, Herston, Qld, Australia. [Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA. [Horan, John T.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA. [Kennedy-Nasser, Alana A.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Kitko, Carrie] Univ Michigan, Ann Arbor, MI 48109 USA. [Kurtzberg, Joanne] Duke Univ, Durham, NC USA. [Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA USA. [O'Brien, Tracey] Sydney Childrens Hosp, Sydney, NSW, Australia. [Pulsipher, Michael A.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Smith, Franklin O.] Univ Cincinnati, Inst Canc, Cincinnati, OH USA. [Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Carpenter, PA (reprint author), Fred Hutchinson Canc Res Ctr, D5-290,1024 Fairview Ave N, Seattle, WA 98109 USA. EM pcarpent@fhcrc.org FU Public Health Service from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases [U24-CA76518]; Health Resources and Services Administration [HHSH234200637015C] FX Supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases and HHSH234200637015C, from the Health Resources and Services Administration. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 24 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2013 VL 19 IS 6 BP 893 EP 897 DI 10.1016/j.bbmt.2013.02.017 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 156TX UT WOS:000319847900010 PM 23467128 ER PT J AU Bar, M Sandmaier, BM Inamoto, Y Bruno, B Hari, P Chauncey, T Martin, PJ Storb, R Maloney, DG Storer, B Flowers, MED AF Bar, Merav Sandmaier, Brenda M. Inamoto, Yoshihiro Bruno, Benedetto Hari, Parameswaran Chauncey, Thomas Martin, Paul J. Storb, Rainer Maloney, David G. Storer, Barry Flowers, Mary E. D. TI Donor Lymphocyte Infusion for Relapsed Hematological Malignancies after Allogeneic Hematopoietic Cell Transplantation: Prognostic Relevance of the Initial CD3(+) T Cell Dose SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Donor lymphocyte infusion (DLI); Hematopoietic cell transplantation (HCT); CD3(+) T cells; Graft-versus-host disease (GVHD); Adoptive immunotherapy for relapse after HCT ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; LEUKOCYTE INFUSIONS; ADOPTIVE IMMUNOTHERAPY; CHRONIC GRAFT; MULTIPLE-MYELOMA; WORKING PARTY; CHEMOTHERAPY AB The impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patients with chronic myeloid leukemia but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3(+) cell dose on graft-versus-host disease (GVHD) and overall survival after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high- or reduced-intensity conditioning. The cohort included 225 patients. Initial DLI CD3(+) cell dose per kilogram of recipient body weight was <= 1 x 10(7) (n = 84; group A), >1.0 to <10 x 10(7) (n = 58; group B), and >= 10 x 10(7) (n = 66; group C). The initial cell dose was unknown for the remaining 17 patients. Cumulative incidence rates of GVHD at 12 months after DLI were 21%, 45%, and 55% for groups A, B, and C, respectively. Multivariate analysis showed that initial DLI CD3(+) cell >= 10 x 10(7) dose per kilogram is associated with an increased risk of GVHD after DLI (P = .03). Moreover, an initial DLI CD3(+) cell dose of 10 x 10(7) or higher did not decrease the risk of relapse and did not improve overall survival. Thus, these results support the use of less than 10 x 10(7) CD3(+) cell per kilogram as the initial cell dose of DLI for treatment of persistent or recurrent hematological malignancy after HCT. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Bar, Merav; Sandmaier, Brenda M.; Inamoto, Yoshihiro; Chauncey, Thomas; Martin, Paul J.; Storb, Rainer; Maloney, David G.; Storer, Barry; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Bar, Merav; Sandmaier, Brenda M.; Chauncey, Thomas; Martin, Paul J.; Storb, Rainer; Maloney, David G.; Flowers, Mary E. D.] Univ Washington, Dept Med, Seattle, WA USA. [Bruno, Benedetto; Storer, Barry] Univ Turin, Turin, Italy. [Hari, Parameswaran] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Storer, Barry] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Bar, M (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024, Seattle, WA 98109 USA. EM mbar@u.washington.edu OI Hari, Parameswaran/0000-0002-8800-297X FU National Institutes of Health [CA78902, CA018029] FX This study was supported in part by grants CA78902 and CA018029 from the National Institutes of Health. NR 36 TC 25 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2013 VL 19 IS 6 BP 949 EP 957 DI 10.1016/j.bbmt.2013.03.001 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 156TX UT WOS:000319847900018 PM 23523892 ER PT J AU Pidala, J Chai, XY Martin, P Inamoto, Y Cutler, C Palmer, J Weisdorf, D Pavletic, S Arora, M Jagasia, M Jacobsohn, D Lee, SJ AF Pidala, Joseph Chai, Xiaoyu Martin, Paul Inamoto, Yoshihiro Cutler, Corey Palmer, Jeanne Weisdorf, Daniel Pavletic, Steven Arora, Mukta Jagasia, Madan Jacobsohn, David Lee, Stephanie J. TI Hand Grip Strength and 2-Minute Walk Test in Chronic Graft-versus-Host Disease Assessment: Analysis from the Chronic GVHD Consortium SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hand grip strength; Two minute walk test; Chronic graft vs. host disease ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HUMAN ACTIVITY PROFILE; CLINICAL-TRIALS; PROGNOSTIC VALUE; PINCH STRENGTH; CRITERIA AB Hand grip strength (HGS) and the 2-minute walk test (2MWT) have been proposed as elements of chronic graft-versus-host disease (GVHD) assessment in clinical trials. Using all available data (n = 584 enrollment visits, 1689 follow-up visits, total of 2273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, MOS 36-Item Short-Form Health Survey [SF-36], and Functional Assessment of Cancer Therapy [FACT]-Bone Marrow Transplantation quality of life instruments and Human Activity Profile [HAP]), chronic GVHD global severity (National Institutes of Health global score, clinician global score; and patient-reported global score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival, nonrelapse mortality, and failure-free survival) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all P < .001). Fewer associations were detected with the HGS. The 2MWT and HGS both had significant association with global chronic GVHD severity. In multivariable analysis, 2MWT was significantly associated with overall survival, nonrelapse mortality, and failure-free survival, whereas no association was found for HGS. 2MWT and HGS were not sensitive to National Institutes of Health or clinician-reported response. Based on independent association with mortality, these data support the importance of the 2MWT for identification of high-risk chronic GVHD patients. However, change in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in clinical trials. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Chai, Xiaoyu; Martin, Paul; Inamoto, Yoshihiro; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Weisdorf, Daniel; Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Pavletic, Steven] NCI, Bethesda, MD 20892 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Pidala, J (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Joseph.pidala@moffitt.org FU NIAID [U54 AI 083028]; [CA 118953] FX Supported by grant CA 118953 (principle investigator, S.J.L.) and NIAID U54 AI 083028 (principle investigator, S.J.L.). NR 38 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2013 VL 19 IS 6 BP 967 EP 972 DI 10.1016/j.bbmt.2013.03.014 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 156TX UT WOS:000319847900020 PM 23542686 ER PT J AU Chen, YB Coughlin, E Kennedy, KF Alyea, EP Armand, P Attar, EC Ballen, KK Cutler, C Dey, BR Koreth, J McAfee, SL Spitzer, TR Antin, JH Soiffer, RJ Ho, VT AF Chen, Yi-Bin Coughlin, Erin Kennedy, Kevin F. Alyea, Edwin P. Armand, Philippe Attar, Eyal C. Ballen, Karen K. Cutler, Corey Dey, Bimalangshu R. Koreth, John McAfee, Steven L. Spitzer, Thomas R. Antin, Joseph H. Soiffer, Robert J. Ho, Vincent T. TI Busulfan Dose Intensity and Outcomes in Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation for Myelodysplastic Syndrome or Acute Myeloid Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Busulfan; Reduced intensity transplant; Conditioning regimen ID ACUTE MYELOGENOUS LEUKEMIA; CONDITIONING REGIMEN; COMPLETE REMISSION; PATIENTS OLDER; AGE; CYTOGENETICS; STANDARD; IMPACT; GVHD; MDS AB Comparisons of myeloablative conditioning versus reduced-intensity conditioning (RIC) have demonstrated a tradeoff between relapse and toxicity. Dose intensity across RIC regimens vary and may affect treatment outcomes. In this retrospective analysis, we investigated the effect of i.v. busulfan dosing (total dose 3.2 mg/kg versus 6.4 mg/kg) in RIC regimens that combined fludarabine and busulfan on outcomes in patients who were undergoing hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). A total of 217 consecutive patients with MDS or AML underwent first busulfan and fludarabine RIC peripheral blood stem cell transplantation from well-matched related or unrelated donors at our institutions between 2004 and 2009. Of the 217 patients, 135 patients received Bu1 (3.2 mg/kg of busulfan) and 82 patients received Bu2 (6.4 mg/kg of busulfan), both with daily fludarabine (30 mg/m(2)/day for 4 days). The choice of RIC regimen was based on temporal institutional standard, enrollment on protocols, and physician choice. Patients had similar characteristics with a few notable differences: Patients who received Bu1 were younger (median age 61 versus 64 years, P <. 001), received more single-antigen mismatched unrelated grafts (14.1% versus 1.2%, P <. 001), received more sirolimus-based graft-versus-host disease (GVHD) prophylaxis regimens (63% versus 45%, P < .0001), received less antithymocyte globulin for GVHD prophylaxis (0% versus 22%, P < .001), and had less enrollment on a clinical trial that used prophylactic rituximab for the prevention of chronic GVHD (2.2% versus 11.0%, P = .011). Clinical disease status was similar between the groups. Median follow-up for survivors was 4.4 years for Bu1 and 3.2 years for Bu2. Because of the differences in characteristics, the 2 groups were compared with the adjustment of a propensity score that predicted Bu2 to account for measured differences. The day +200 cumulative incidence rates of grades II to IV acute GVHD (Bu1, 17%, versus Bu2, 8.5%; hazard ratio [HR], .56; 95% confidence interval [CI], .22 to 1.41; P = .22) or grades III to IV acute GVHD (Bu1, 6.7%, versus Bu2, 4.9%) were not different. The 2-year cumulative incidence of chronic GVHD was not significantly different between Bu1 and Bu2 (41.5% versus 28%, respectively; HR, .70; CI, .42 to 1.17; P = .09). Two-year nonrelapse mortality rates were similar for Bu1 and Bu2 (8.9% versus 9.8%, respectively; HR, .80; CI, .29 to 2.21; P = .67). Two-year progression-free survival and overall survival were also similar between Bu1 and Bu2 (progression-free survival: 40.6% versus 39.3%, respectively; HR, .82; CI, .57 to 1.30; P = .33; and overall survival: 47.4% versus 48.8%, respectively; HR, .96; CI, .64 to 1.44; P = .85). Subset analysis defined by clinical disease and cytogenetic risk with the propensity risk score applied suggest that in patients with high clinical disease risk and nonadverse cytogenetics, the higher dose busulfan RIC regimen may be of marginal benefit (2-year progression-free survival: HR, .54; CI, .29 to 1.03; P = .062). For the majority of patients with MDS or AML undergoing busulfan and fludarabine RIC peripheral blood stem cell transplantation, however, the dose of busulfan (3.2 mg/kg versus 6.4 mg/kg) is not associated with significant differences in overall outcomes. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Chen, Yi-Bin; Coughlin, Erin; Attar, Eyal C.; Ballen, Karen K.; Dey, Bimalangshu R.; McAfee, Steven L.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Alyea, Edwin P.; Armand, Philippe; Cutler, Corey; Koreth, John; Antin, Joseph H.; Soiffer, Robert J.; Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Chen, YB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplant Unit,Canc Ctr, Cox 106,55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU MGH Mary "Nan" DiPiero Leukemia Research Fund; MGH Clinical Research Scholar Award; Otsuka Pharmaceuticals, Inc. FX This research was supported by the MGH Mary "Nan" DiPiero Leukemia Research Fund. Y.C. is supported by an MGH Clinical Research Scholar Award.; Y.C. reports receiving consulting fees and funding to conduct clinical trials from Otsuka Pharmaceuticals, Inc. The remaining authors have no relevant conflicts of interest to disclose. NR 21 TC 21 Z9 21 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2013 VL 19 IS 6 BP 981 EP 987 DI 10.1016/j.bbmt.2013.03.016 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 156TX UT WOS:000319847900022 PM 23562738 ER PT J AU Chen, YB Cutler, CS AF Chen, Y-B Cutler, C. S. TI Biomarkers for acute GVHD: can we predict the unpredictable? SO BONE MARROW TRANSPLANTATION LA English DT Review DE GVHD; biomarkers; transplant ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; SERUM CYTOKINE LEVELS; CLINICAL-TRIALS NETWORK; NECROSIS-FACTOR-ALPHA; BLOOD UREA NITROGEN; SOLUBLE INTERLEUKIN-2-RECEPTOR; COMPLICATIONS; MIGRATION AB Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-alpha, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3 alpha, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized. C1 [Chen, Y-B] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Boston, MA 02114 USA. [Cutler, C. S.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Cox 106, Boston, MA 02114 USA. EM ychen6@partners.org FU Millennium Pharmaceuticals, Inc.; Seattle Genetics FX Dr Y-B Chen has received funding for clinical trials from Millennium Pharmaceuticals, Inc. and has served as a consultant for and received funding for clinical trials from Seattle Genetics. NR 53 TC 13 Z9 14 U1 0 U2 6 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 JUN PY 2013 VL 48 IS 6 BP 755 EP 760 DI 10.1038/bmt.2012.143 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 158JW UT WOS:000319967200002 PM 22863728 ER PT J AU Shaughnessy, P Uberti, J Devine, S Maziarz, RT Vose, J Micallef, I Jacobsen, E McCarty, J Stiff, P Artz, A Ball, ED Berryman, R Dugan, M Joyce, R Hsu, FJ Johns, D McSweeney, P AF Shaughnessy, P. Uberti, J. Devine, S. Maziarz, R. T. Vose, J. Micallef, I. Jacobsen, E. McCarty, J. Stiff, P. Artz, A. Ball, E. D. Berryman, R. Dugan, M. Joyce, R. Hsu, F. J. Johns, D. McSweeney, P. TI Plerixafor and G-CSF for autologous stem cell mobilization in patients with NHL, Hodgkin's lymphoma and multiple myeloma: results from the expanded access program SO BONE MARROW TRANSPLANTATION LA English DT Article DE plerixafor; mobilization; autologous transplant ID BONE-MARROW TRANSPLANTATION; RANDOMIZED TRIAL; CHEMOTHERAPY; ALGORITHM; KINETICS AB Before US regulatory approval, an expanded access program provided plerixafor to patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma (MM) who had not previously failed mobilization and were otherwise candidates for auto-SCT. Patients received granulocyte-CSF (G-CSF) 10 mcg/kg daily and plerixafor 0.24 mg/kg starting on day 4 with apheresis on day 5; all repeated daily until collection was complete. Overall, 104 patients received >= 1 dose of plerixafor. The addition of plerixafor to G-CSF resulted in a median threefold increase in peripheral blood CD34+ cell count between days 4 and 5. Among 43 NHL patients, 74% met the target of >= 5 x 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-5 days); among 7 HD patients, 57% met the target of >= 5 x 10(6) CD34+ cells/kg (median, 2 days apheresis, range 1-3); and among 54 MM patients, 89% met the target of >= 6 x 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-4). Overall, 93% of patients had >= 2 x 10(6) CD34+ cells/kg collected within 1-3 days. Plerixafor-related toxicities were minimal. Engraftment kinetics, graft durability and transplant outcomes demonstrated no unexpected outcomes. Efficacy and safety results were similar to results in phase II and III clinical trials. C1 [Shaughnessy, P.] Texas Transplant Inst, San Antonio, TX 78229 USA. [Uberti, J.] Karmanos Canc Inst, Detroit, MI USA. [Devine, S.] Ohio State Univ, Dept Internal Med Hematol Oncol, Columbus, OH 43210 USA. [Maziarz, R. T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Vose, J.] Univ Nebraska Med Ctr, Omaha, NE USA. [Micallef, I.] Mayo Clin, Rochester, MN USA. [Jacobsen, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McCarty, J.] Virginia Commonwealth Univ, Richmond, VA USA. [Stiff, P.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Artz, A.] Univ Chicago, Chicago, IL 60637 USA. [Ball, E. D.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Berryman, R.] Baylor Blood & Marrow Transplant Ctr, Dallas, TX USA. [Dugan, M.] Indiana Blood & Marrow Transplantat, Beech Grove, IN USA. [Joyce, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hsu, F. J.; Johns, D.] Sanofi Oncol, Cambridge, MA USA. [McSweeney, P.] Rocky Mt Canc Ctr, Denver, CO USA. RP Shaughnessy, P (reprint author), Texas Transplant Inst, 4410 Med Dr Suite 410, San Antonio, TX 78229 USA. EM paul.shaughnessy@mhshealth.com; paul.shaughnessy@mhshealth.com FU Sanofi Oncology; Genzyme; Sanofi/Genzyme FX This study was sponsored by Sanofi Oncology (previously Genzyme Corporation). PS, RTM, JMC, SD, MD and PMS received honoraria and research funding from Genzyme. IM, JV and PS received research funding from Sanofi/Genzyme. FJH is a former Genzyme employee and is now an employee of Zyngenia, Inc. DJ is an employee of Sanofi Oncology (formerly Genzyme). All the other author declare no conflicts of interest. NR 16 TC 14 Z9 14 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2013 VL 48 IS 6 BP 777 EP 781 DI 10.1038/bmt.2012.219 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 158JW UT WOS:000319967200005 PM 23178544 ER PT J AU Akpek, G Pasquini, MC Logan, B Agovi, MA Lazarus, HM Marks, DI Bornhaeuser, M Ringden, O Maziarz, RT Gupta, V Popat, U Maharaj, D Bolwell, BJ Rizzo, JD Ballen, KK Cooke, KR McCarthy, PL Ho, VT AF Akpek, G. Pasquini, M. C. Logan, B. Agovi, M-A Lazarus, H. M. Marks, D. I. Bornhaeueser, M. Ringden, O. Maziarz, R. T. Gupta, V. Popat, U. Maharaj, D. Bolwell, B. J. Rizzo, J. D. Ballen, K. K. Cooke, K. R. McCarthy, P. L. Ho, V. T. CA CIBMTR TI Effects of spleen status on early outcomes after hematopoietic cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE engraftment; splenectomy; spleen; SCT; myeloproliferative disease ID BONE-MARROW-TRANSPLANTATION; CHRONIC GRANULOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; VERSUS-HOST DISEASE; PRIMARY MYELOFIBROSIS; RADIATION INJURY; HLA MISMATCH; SPLENECTOMY; STEM; GRAFT AB To assess the impact of spleen status on engraftment, and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil engraftment (NE) and platelet engraftment (PE) were 15 vs 18 days and 22 vs 24 days for the SP and NS groups, respectively (P < 0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds ratio of days +14 and +21 NE and day +28 PE were 3.26, 2.25 and 1.28 for SP, and 0.56, 0.55, and 0.82 for SM groups compared to NS (P < 0.001), respectively. Among patients with SM, use of peripheral blood grafts improved NE at day +21, and CD34+ cell dose >5.7 x 10(6)/kg improved PE at day +28. After adjusting variables by Cox regression, the incidence of GVHD and OS were not different among groups. SM is associated with delayed engraftment, whereas SP prior to HCT facilitates early engraftment without having an impact on survival. C1 [Akpek, G.] Univ Maryland, Marlene & Stewart Greenbaum Canc Ctr, Baltimore, MD 21201 USA. [Pasquini, M. C.; Logan, B.; Agovi, M-A; Rizzo, J. D.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Lazarus, H. M.; Cooke, K. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Marks, D. I.] Bristol Childrens Hosp, Bristol, Avon, England. [Bornhaeueser, M.] Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Ringden, O.] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Maziarz, R. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gupta, V.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Popat, U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Maharaj, D.] Bethesda Hlth City, Boynton Beach, FL USA. [Bolwell, B. J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Ballen, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, P. L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Ho, V. T.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Akpek, G (reprint author), Banner MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy Program, 2940 E Banner Gateway Dr, Gilbert, AZ 85234 USA. EM GAkpek@mdanderson.org FU Public Health Service from the National Cancer Institute [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia and Lymphoma Society; the Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense or any other agency of the U.S. Government. NR 30 TC 17 Z9 17 U1 1 U2 6 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 JUN PY 2013 VL 48 IS 6 BP 825 EP 831 DI 10.1038/bmt.2012.249 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 158JW UT WOS:000319967200014 PM 23222382 ER PT J AU Culley, DJ Cotran, EK Karlsson, E Palanisamy, A Boyd, JD Xie, Z Crosby, G AF Culley, D. J. Cotran, E. K. Karlsson, E. Palanisamy, A. Boyd, J. D. Xie, Z. Crosby, G. TI Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE astrocytes; isoflurane ID VOLATILE ANESTHETICS; NERVOUS-SYSTEM; CELLS; BRAIN; GLIA; ACTIVATION; MEMORY; NEUROGENESIS; PERSPECTIVE; IMPAIRMENT AB More than half of the cells in the brain are glia and yet the impact of general anaesthetics on these cells is largely unexamined. We hypothesized that astroglia, which are strongly implicated in neuronal well-being and synapse formation and function, are vulnerable to adverse effects of isoflurane. Cultured rat astrocytes were treated with 1.4 isoflurane in air or air alone for 4 h. Viability, proliferation, and cytoskeleton were assessed by colorimetric assay, immunocytochemistry, or a migration assay at the end of treatment or 2 days later. Also, primary rat cortical neurones were treated for 4 days with conditioned medium from control [astrocyte-conditioned media (ACM)], or isoflurane-exposed astrocytes (Iso-ACM) and synaptic puncta were assessed by synapsin 1 and PSD-95 immunostaining. By several measures, isoflurane did not kill astrocytes. Nor, based on incorporation of a thymidine analogue, did it inhibit proliferation. Isoflurane had no effect on F-actin but reduced expression of -tubulin and glial fibrillary acidic protein both during exposure (P0.05 and P0.001, respectively) and 2 days later (P0.01), but did not impair astrocyte motility. ACM increased formation of PSD-95 but not synapsin 1 positive puncta in neuronal cultures, and Iso-ACM was equally effective. Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro, but did not affect their viability, proliferation, motility, and ability to support synapses. C1 [Culley, D. J.; Cotran, E. K.; Karlsson, E.; Palanisamy, A.; Crosby, G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Boyd, J. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard NeuroDiscovery Ctr,LDDN, Cambridge, MA 02139 USA. [Xie, Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Culley, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. EM dculley@zeus.bwh.harvard.edu FU National Institutes of Health [K08 GM077057, R01 GM088817]; Milton Fund of Harvard University; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA FX This study was supported by National Institutes of Health grants K08 GM077057 (D.J.C.), R01 GM088817 (G.C.), the Milton Fund of Harvard University (D.J.C.), and the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA. NR 38 TC 19 Z9 20 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 2013 VL 110 SU 1 SI SI BP 19 EP 28 DI 10.1093/bja/aet169 PG 10 WC Anesthesiology SC Anesthesiology GA 156JK UT WOS:000319817700004 ER PT J AU Zhang, L Zhang, J Yang, L Dong, Y Zhang, Y Xie, Z AF Zhang, L. Zhang, J. Yang, L. Dong, Y. Zhang, Y. Xie, Z. TI Isoflurane and sevoflurane increase interleukin-6 levels through the nuclear factor-kappa B pathway in neuroglioma cells SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthetic; interleukin-6; NF-kappa B ID AMYLOID PROTEIN-LEVELS; PYRROLIDINE DITHIOCARBAMATE; COGNITIVE DYSFUNCTION; CYTOKINE EXPRESSION; INDUCED APOPTOSIS; AGED RATS; ACTIVATION; ANESTHETICS; BEHAVIOR; BRAIN AB Isoflurane can increase pro-inflammatory cytokine interleukin (IL)-6 levels. However, the up-stream mechanism remains unknown. Nuclear factor-kappa B (NF-B) promotes the generation of pro-inflammatory cytokines. We examined the effects of isoflurane and sevoflurane on the NF-B signalling pathway and its association with IL-6 levels in cultured cells. H4 human neuroglioma cells (H4 cells), and mouse primary neurones and microglia were treated with 2 isoflurane or 4.1 sevoflurane for 6 h, for analysis of IL-6 and NF-B. Pyrrolidine dithiocarbamate (an NF-B inhibitor) or 2-deoxy-d-glucose (2-DG) (an inhibitor of glucose glycolysis) was applied 1 h before anaesthetic treatment. Isoflurane or sevoflurane treatment increased the levels of IL-6 [isoflurane: 410 (54); sevoflurane: 290 (24)], the nuclear levels of NF-B [isoflurane: 170 (36); sevoflurane: 320 (30)], and the transcription activity of NF-B in H4 cells. Moreover, isoflurane enhanced the transcription activity of NF-B in mouse microglia, but not primary neurones. Finally, pyrrolidine dithiocarbamate and 2-DG attenuated isoflurane-induced increases in IL-6 and NF-B, and the transcription activity of NF-B. These studies in H4 cells suggest that the NF-B signalling pathway could contribute to isoflurane or sevoflurane-induced neuroinflammation. This could lead to the targeted intervention of anaesthetic-induced neuroinflammation. C1 [Zhang, L.; Zhang, J.; Yang, L.; Dong, Y.; Zhang, Y.; Xie, Z.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Zhang, L.; Zhang, J.; Yang, L.; Dong, Y.; Zhang, Y.; Xie, Z.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Zhang, L.] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Anesthesiol, Shanghai 200011, Peoples R China. [Zhang, J.] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Anesthesiol, Tongji Med Coll, Wuhan 430030, Peoples R China. RP Xie, Z (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health, Bethesda, MD, USA [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, IL, USA; Cure Alzheimer's Fund, Wellesley, MA, USA FX This research was supported by R21AG038994, R01 GM088801 and R01 AG041274 from National Institutes of Health, Bethesda, MD, USA; investigator-initiated research grant from Alzheimer's Association, Chicago, IL, USA; and Cure Alzheimer's Fund, Wellesley, MA, USA to Z.X. Isoflurane and sevoflurane were generously provided by the Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. These studies are attributed to the Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School. NR 41 TC 33 Z9 35 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 2013 VL 110 SU 1 SI SI BP 82 EP 91 DI 10.1093/bja/aet115 PG 10 WC Anesthesiology SC Anesthesiology GA 156JK UT WOS:000319817700010 ER PT J AU Wu, B Hur, S AF Wu, Bin Hur, Sun TI Viral counterattack against the host innate immune system SO CELL RESEARCH LA English DT Editorial Material ID PARAMYXOVIRUS V PROTEINS; DSRNA RECOGNITION; MDA5 FILAMENTS; RIG-I; RNA C1 [Wu, Bin; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wu, Bin; Hur, Sun] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM hur@idi.harvard.edu RI Wu, Bin/C-4715-2015 NR 10 TC 2 Z9 2 U1 0 U2 3 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JUN PY 2013 VL 23 IS 6 BP 735 EP 736 DI 10.1038/cr.2013.32 PG 2 WC Cell Biology SC Cell Biology GA 156FL UT WOS:000319807100002 PM 23478300 ER PT J AU Gupta, H Ramanan, B Gupta, PK Fang, X Polich, A Modrykamien, A Schuller, D Morrow, LE AF Gupta, Himani Ramanan, Bala Gupta, Prateek K. Fang, Xiang Polich, Ann Modrykamien, Ariel Schuller, Dan Morrow, Lee E. TI Impact of COPD on Postoperative Outcomes Results From a National Database SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; ABDOMINAL WOUND DEHISCENCE; AFFAIRS SURGICAL RISK; NUTRITIONAL-STATUS; NONCARDIAC SURGERY; PROGNOSTIC VALUE; RENAL-FAILURE; OLDER-ADULTS; MORTALITY; CARE AB Background: Although COPD affects large sections of the population, its effects on postoperative outcomes have not been rigorously studied. The objectives of this study were to describe the prevalence of COPD in patients undergoing surgery and to analyze the associations between COPD and postoperative morbidity, mortality, and hospital length of stay. Methods: Patients with COPD who underwent surgery were identified from the National Surgical Quality Improvement Program database (2007-2008). Univariate and multivariate analyses were performed on this multicenter, prospective data set (N = 468,795). Results: COPD was present in 22,576 patients (4.82%). These patients were more likely to be older, men, white, smokers, and taking corticosteroids and had a lower BMI (P <.0001 for each). Median length of stay was 4 days for patients with COPD vs 1 day in those without COPD (P <.0001). Thirty-day morbidity rates were 25.8% and 10.2% for patients with and without COPD, respectively (P <.0001). Thirty-day death rates were 6.7% and 1.4% for patients with and without COPD, respectively (P <.0001). After controlling for >50 comorbidities through logistic regression modeling, COPD was independently associated with higher postoperative morbidity (OR, 1.35; 95% CI, 1.30-1.40; P <.0001) and mortality (OR, 1.29; 95% CI, 1.19-1.39; P <.0001). Multivariate analyses with each individual postoperative complication as the outcome of interest showed that COPD was associated with increased risk for postoperative pneumonia, respiratory failure, myocardial infarction, cardiac arrest, sepsis, return to the operating room, and renal insufficiency or failure (P <.05 for each). Conclusions: COPD is common among patients undergoing surgery and is associated with increased morbidity, mortality, and length of stay. C1 [Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Ramanan, Bala] Creighton Univ, Dept Surg, Omaha, NE 68178 USA. [Fang, Xiang] Creighton Univ, Biostat Core, Omaha, NE 68178 USA. [Polich, Ann] Creighton Univ, Dept Med, Omaha, NE 68178 USA. [Modrykamien, Ariel; Schuller, Dan; Morrow, Lee E.] Creighton Univ, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA. [Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA. RP Gupta, PK (reprint author), Univ Wisconsin Hosp & Clin, Dept Surg, 600 Highland Ave, Madison, WI 53792 USA. EM pgupta@uwhealth.org NR 42 TC 21 Z9 23 U1 1 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 JUN PY 2013 VL 143 IS 6 BP 1599 EP 1606 DI 10.1378/chest.12-1499 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 159UN UT WOS:000320072900018 PM 23287892 ER PT J AU Kinsey, CM Folch, E Majid, A Channick, CL AF Kinsey, C. Matthew Folch, Erik Majid, Adnan Channick, Colleen L. TI Evaluation and Management of Pill Aspiration Case Discussion and Review of the Literature SO CHEST LA English DT Editorial Material ID IRON TABLET; BRONCHIAL NECROSIS; FERROUS SULFATE; FOREIGN-BODY; INHALATION; LUNG AB Pill aspiration represents a unique type of foreign body aspiration requiring a distinct diagnostic and therapeutic approach. In many cases, the "foreign body" itself may no longer be present, whereas the airway manifestations may persist for months to years. Limited data exist to guide management decisions. We report two cases of severe airway injury secondary to pill aspiration and provide a review of the literature. Endobronchial surveillance may be important to identify impending airway obstruction via secretions, edema, granulation tissue, or fibrotic stricture. In many cases, the airway sequelae of pill aspiration can be effectively managed with bronchoscopy. C1 [Kinsey, C. Matthew; Channick, Colleen L.] Massachusetts Gen Hosp, Pulm Special Procedures Unit, Boston, MA 02114 USA. [Folch, Erik; Majid, Adnan] Beth Israel Deaconess Med Ctr, Div Thorac Surg & Intervent Pulmonol, Boston, MA 02215 USA. [Kinsey, C. Matthew; Folch, Erik; Majid, Adnan; Channick, Colleen L.] Harvard Univ, Sch Med, Boston, MA USA. RP Channick, CL (reprint author), Massachusetts Gen Hosp, Pulm Special Procedures Unit, 55 Fruit St,Bigelow 952, Boston, MA 02114 USA. EM cchannick@partners.org OI Folch, Erik/0000-0001-7076-7328 NR 16 TC 7 Z9 7 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2013 VL 143 IS 6 BP 1791 EP 1795 DI 10.1378/chest.12-1571 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 159UN UT WOS:000320072900043 PM 23732590 ER PT J AU Levsky, JM Moy, MP Haramati, LB AF Levsky, Jeffrey M. Moy, Matthew P. Haramati, Linda B. TI Basis of Estimating Pleural Effusion Size on CT Scan Reasonable Grouping of Volume Percentage Response SO CHEST LA English DT Letter C1 [Levsky, Jeffrey M.; Haramati, Linda B.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Levsky, Jeffrey M.; Haramati, Linda B.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Moy, Matthew P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Levsky, JM (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 111 E 210 St, Bronx, NY 10467 USA. EM jlevsky@montefiore.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2013 VL 143 IS 6 BP 1839 EP 1840 DI 10.1378/chest.13-0569 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 159UN UT WOS:000320072900060 PM 23732611 ER PT J AU Oberg, K Casanovas, O Castano, JP Chung, D Delle Fave, G Denefle, P Harris, P Khan, MS Kulke, MH Scarpa, A Tang, LH Wiedenmann, B AF Oberg, Kjell Casanovas, Oriol Castano, Justo P. Chung, Daniel Delle Fave, Gianfranco Denefle, Patrice Harris, Philip Khan, Mohid S. Kulke, Matthew H. Scarpa, Aldo Tang, Laura H. Wiedenmann, Bertram TI Molecular Pathogenesis of Neuroendocrine Tumors: Implications for Current and Future Therapeutic Approaches SO CLINICAL CANCER RESEARCH LA English DT Review ID PANCREATIC ENDOCRINE TUMORS; SOMATOSTATIN RECEPTORS; REVEALS ALTERATIONS; MESSENGER-RNA; BREAST-CANCER; MTOR PATHWAY; CELLS; EXPRESSION; RESISTANCE; INHIBITION AB The treatment landscape and biologic understanding of neuroendocrine tumors ( NET) has shifted dramatically in recent years. Recent studies have shown that somatostatin analogues have the potential not only to control symptoms of hormone hypersecretion but also have the ability to slow tumor growth in patients with advanced carcinoid. The results of clinical trials have further shown that the VEGF pathway inhibitor sunitinib and the mTOR inhibitor everolimus have efficacy in patients with advanced pancreatic NETs. The efficacy of these targeted therapies in NET suggests that the molecular characterization of NETs may provide an avenue to predict both which patients may benefit most from the treatment and to overcome potential drug resistance. Recent genomic studies of NETs have further suggested that pathways regulating chromatin remodeling and epigenetic modification may play a key role in regulating NET growth. These observations offer the potential for new therapeutic and diagnostic advances for patients with NET. (C) 2013 AACR. C1 [Oberg, Kjell] Univ Uppsala Hosp, Dept Endocrine Oncol, S-75185 Uppsala, Sweden. [Casanovas, Oriol] Catalan Inst Oncol IDIBELL, Translat Res Lab, Tumor Angiogenesis Grp, Barcelona, Spain. [Castano, Justo P.] Univ Cordoba, Hosp Univ Reina Sofia, IMIBIC, Dept Cell Biol Physiol & Immunol, Cordoba, Spain. [Castano, Justo P.] CIBERobn, Cordoba, Spain. [Chung, Daniel] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, Daniel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kulke, Matthew H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Delle Fave, Gianfranco] Univ Roma La Sapienza, Sch Med, Dept Translat Med, Rome, Italy. [Scarpa, Aldo] Univ & Hosp Trust Verona, Dept Pathol & Diagnost, Verona, Italy. [Scarpa, Aldo] Univ & Hosp Trust Verona, ARC NET Ctr Appl Res Canc, Verona, Italy. [Denefle, Patrice] Ipsen Ltd, Translat Sci, Les Ulis, France. [Harris, Philip] Ipsen Ltd, Sci Affairs, Slough, Berks, England. [Khan, Mohid S.] Univ Coll London Hosp, Div Gastrointestinal Serv, London, England. [Tang, Laura H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Wiedenmann, Bertram] Charite, Dept Internal Med, Div Gastroenterol Hepatol & Metab, Berlin, Germany. RP Oberg, K (reprint author), Univ Uppsala Hosp, Dept Endocrine Oncol, S-75185 Uppsala, Sweden. EM kjell.oberg@medsci.uu.se RI Castano, Justo P/A-7124-2010; scarpa, aldo/K-6832-2016; OI Castano, Justo P/0000-0002-3145-7287; scarpa, aldo/0000-0003-1678-739X; Casanovas, Oriol/0000-0002-4298-3995 FU Ipsen; Novartis FX K. Oberg has received honoraria from the speakers' bureau and is a consultant/advisory board member of USD, EUR. O. Casanovas has received honoraria from the speakers' bureaus of Ipsen and Pfizer and is a consultant/advisory board member of TEVA and Ipsen. J.P. Castano has a commercial research grant from Ipsen and has received honoraria from the speakers' bureaus of Ipsen and Novartis. D. Chung is a consultant/advisory board member of Ipsen. M.S. Khan has received honoraria from the speakers' bureaus of Ipsen and Novartis. M.H. Kulke has commercial research grants from Novartis and Ipsen and is a consultant/advisory board member of Ipsen, Novartis, Pfizer, and Lexicon. B. Wiedenmann has received honoraria from the speakers' bureaus of Pfizer, Novartis, and IOSEN Biotech and is a consultant/advisory board member of Pfizer, Novartis, and Ipsen. No potential conflicts of interest were disclosed by the other authors. NR 67 TC 28 Z9 29 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 2842 EP 2849 DI 10.1158/1078-0432.CCR-12-3458 PG 8 WC Oncology SC Oncology GA 155FF UT WOS:000319732000010 PM 23459719 ER PT J AU Ouillette, P Saiya-Cork, K Seymour, E Li, C Shedden, K Malek, SN AF Ouillette, Peter Saiya-Cork, Kamlai Seymour, Erlene Li, Cheng Shedden, Kerby Malek, Sami N. TI Clonal Evolution, Genomic Drivers, and Effects of Therapy in Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; SHORT SURVIVAL; COPY NUMBER; MDM2 INHIBITORS; MUTATION STATUS; P53 MUTATIONS; GENE MUTATION; WIDE ANALYSIS; ABERRATIONS; RESISTANCE AB Purpose: The identification of gene mutations and structural genomic aberrations that are critically involved in chronic lymphocytic leukemia (CLL) pathogenesis is still evolving. One may postulate that genomic driver lesions with effects on CLL cell proliferation, apoptosis thresholds, or chemotherapy resistance should increase in frequency over time when measured sequentially in a large CLL cohort. Experimental Design: We sequentially sampled a large well-characterized CLL cohort at a mean of 4 years between samplings and measured acquired copy number aberrations (aCNA) and LOH using single-nucleotide polymorphism (SNP) 6.0 array profiling and the mutational state of TP53, NOTCH1, and SF3B1 using Sanger sequencing. The paired analysis included 156 patients, of whom 114 remained untreated and 42 received intercurrent therapies, predominantly potent chemoimmunotherapy, during the sampling interval. Results: We identify a strong effect of intercurrent therapies on the frequency of acquisition of aCNAs in CLL. Importantly, the spectrum of acquired genomic changes was largely similar in patients who did or did not receive intercurrent therapies; therefore, various genomic changes that become part of the dominant clones are often already present in CLL cell populations before therapy. Furthermore, we provide evidence that therapy of CLL with preexisting TP53 mutations results in outgrowth of genomically very complex clones, which dominate at relapse. Conclusions: Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations. (c) 2013 AACR. C1 [Ouillette, Peter; Saiya-Cork, Kamlai; Seymour, Erlene; Malek, Sami N.] Univ Michigan, Div Hematol & Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. [Shedden, Kerby] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Malek, SN (reprint author), Univ Michigan, Div Hematol & Oncol, Dept Internal Med, 1500 E,Med Ctr Dr, Ann Arbor, MI 48109 USA. EM smalek@med.umich.edu FU NIH [CA136537]; Clinical Scholars Award of the Leukemia and Lymphoma Society of America; Translational Research Program of the Leukemia and Lymphoma Society of America; collaborative research grant by the Lymphoma Research Foundation; NIH through the University of Michigan's Cancer Center Support Grant [5 P30 CA46592] FX This work was supported by the NIH through CA136537 (to S.N. Malek), a Clinical Scholars Award of the Leukemia and Lymphoma Society of America (to S.N. Malek), the Translational Research Program of the Leukemia and Lymphoma Society of America (to S.N. Malek), and a collaborative research grant by the Lymphoma Research Foundation. This research is supported (in part) by the NIH through the University of Michigan's Cancer Center Support Grant (5 P30 CA46592). NR 41 TC 30 Z9 30 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 2893 EP 2904 DI 10.1158/1078-0432.CCR-13-0138 PG 12 WC Oncology SC Oncology GA 155FF UT WOS:000319732000015 PM 23620403 ER PT J AU Martin, ES Belmont, PJ Sinnamon, MJ Richard, LG Yuan, J Coffee, EM Roper, J Lee, L Heidari, P Lunt, SY Goel, G Ji, XD Xie, Z Xie, T Lamb, J Weinrich, SL VanArsdale, T Bronson, RT Xavier, RJ Vander Heiden, MG Kan, JLC Mahmood, U Hung, KE AF Martin, Eric S. Belmont, Peter J. Sinnamon, Mark J. Richard, Larissa Georgeon Yuan, Jing Coffee, Erin M. Roper, Jatin Lee, Lydia Heidari, Pedram Lunt, Sophia Y. Goel, Gautam Ji, Xiadong Xie, Zhi Xie, Tao Lamb, John Weinrich, Scott L. VanArsdale, Todd Bronson, Roderick T. Xavier, Ramnik J. Vander Heiden, Matthew G. Kan, Julie L. C. Mahmood, Umar Hung, Kenneth E. TI Development of a Colon Cancer GEMM-Derived Orthotopic Transplant Model for Drug Discovery and Validation SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC COLORECTAL-CANCER; SYNTHETIC LETHAL INTERACTIONS; TARGETED THERAPIES; ONCOGENIC KRAS; MOUSE MODEL; CELLS; RAS; TUMORS; MUTATIONS; PIK3CA AB Purpose: Effective therapies for KRAS-mutant colorectal cancer (CRC) are a critical unmet clinical need. Previously, we described genetically engineered mouse models (GEMM) for sporadic Kras-mutant and non-mutant CRC suitable for preclinical evaluation of experimental therapeutics. To accelerate drug discovery and validation, we sought to derive low-passage cell lines from GEMM Kras-mutant and wild-type tumors for in vitro screening and transplantation into the native colonic environment of immunocompetent mice for in vivo validation. Experimental Design: Cell lines were derived from Kras-mutant and non-mutant GEMM tumors under defined media conditions. Growth kinetics, phosphoproteomes, transcriptomes, drug sensitivity, and metabolism were examined. Cell lines were implanted in mice and monitored for in vivo tumor analysis. Results: Kras-mutant cell lines displayed increased proliferation, mitogen-activated protein kinase signaling, and phosphoinositide-3 kinase signaling. Microarray analysis identified significant overlap with human CRC-related gene signatures, including KRAS-mutant and metastatic CRC. Further analyses revealed enrichment for numerous disease-relevant biologic pathways, including glucose metabolism. Functional assessment in vitro and in vivo validated this finding and highlighted the dependence of Kras-mutant CRC on oncogenic signaling and on aerobic glycolysis. Conclusions: We have successfully characterized a novel GEMM-derived orthotopic transplant model of human KRAS-mutant CRC. This approach combines in vitro screening capability using low-passage cell lines that recapitulate human CRC and potential for rapid in vivo validation using cell line-derived tumors that develop in the colonic microenvironment of immunocompetent animals. Taken together, this platform is a clear advancement in preclinical CRC models for comprehensive drug discovery and validation efforts. (c) 2013 AACR. C1 [Martin, Eric S.; Bronson, Roderick T.] Dana Farber Canc Inst, San Diego, CA USA. [Belmont, Peter J.; Yuan, Jing; Ji, Xiadong; Xie, Zhi; Xie, Tao; Lamb, John; Weinrich, Scott L.; VanArsdale, Todd; Kan, Julie L. C.] Pfizer Global Res & Dev, Oncol Res Unit, San Diego, CA 92121 USA. [Sinnamon, Mark J.; Richard, Larissa Georgeon; Coffee, Erin M.; Roper, Jatin; Lee, Lydia; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA. [Lunt, Sophia Y.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Boston, MA USA. [Heidari, Pedram; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Martin, ES (reprint author), Pfizer Global Res & Dev, 10724 Sci Ctr Dr CB3-2227, San Diego, CA 92121 USA. EM Eric.Martin@pfizer.com; kenneth.hung@tufts.edu OI Lunt, Sophia/0000-0003-4522-6065; Roper, Jatin/0000-0002-8851-1352 FU NCI NIH HHS [U01 CA084301]; NIDDK NIH HHS [K08 DK078033, P30 DK043351, R03 DK088014] NR 46 TC 13 Z9 13 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 2929 EP 2940 DI 10.1158/1078-0432.CCR-12-2307 PG 12 WC Oncology SC Oncology GA 155FF UT WOS:000319732000018 PM 23403635 ER PT J AU Chauhan, D Ray, A Viktorsson, K Spira, J Paba-Prada, C Munshi, N Richardson, P Lewensohn, R Anderson, KC AF Chauhan, Dharminder Ray, Arghya Viktorsson, Kristina Spira, Jack Paba-Prada, Claudia Munshi, Nikhil Richardson, Paul Lewensohn, Rolf Anderson, Kenneth C. TI In Vitro and In Vivo Antitumor Activity of a Novel Alkylating Agent, Melphalan-Flufenamide, against Multiple Myeloma Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID FLUOROPHENYLALANINE ETHYL-ESTER; PRODRUG J1; CLINICAL RESISTANCE; RANDOMIZED-TRIAL; AMINOPEPTIDASE-N; DRUG-RESISTANCE; APOPTOSIS; THALIDOMIDE; INHIBITOR; CHEMOTHERAPY AB Purpose: The alkylating agent melphalan prolongs survival in patients with multiple myeloma; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (mel-flufen), a novel dipeptide prodrug of melphalan in multiple myeloma. Experimental Design: Multiple myeloma cell lines, primary patient cells, and the human multiple myeloma xenograft animal model were used to study the antitumor activity of mel-flufen. Results: Low doses of mel-flufen trigger more rapid and higher intracellular concentrations of melphalan in multiple myeloma cells than are achievable by free melphalan. Cytotoxicity analysis showed significantly lower IC50 of mel-flufen than melphalan in multiple myeloma cells. Importantly, mel-flufen induces apoptosis even in melphalan-and bortezomib-resistant multiple myeloma cells. Mechanistic studies show that siRNA knockdown of aminopeptidase N, a key enzyme mediating intracellular conversion of mel-flufen to melphalan, attenuates anti-multiple myeloma activity of mel-flufen. Furthermore, mel-flufen-induced apoptosis was associated with: (i) activation of caspases and PARP cleavage; (ii) reactive oxygen species generation; (iii) mitochondrial dysfunction and release of cytochrome c; and (iv) induction of DNA damage. Moreover, mel-flufen inhibits multiple myeloma cell migration and tumor-associated angiogenesis. Human multiple myeloma xenograft studies showed amore potent inhibition of tumor growth in mice treated withmel-flufen than mice receiving equimolar doses of melphalan. Finally, combining mel-flufen with lenalidomide, bortezomib, or dexamethasone triggers synergistic anti-multiple myeloma activity. Conclusion: Our preclinical study supports clinical evaluation of mel-flufen to enhance therapeutic potential of melphalan, overcome drug-resistance, and improve multiple myeloma patient outcome. (C) 2013 AACR. C1 [Chauhan, Dharminder; Ray, Arghya; Paba-Prada, Claudia; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Chauhan, Dharminder; Ray, Arghya; Paba-Prada, Claudia; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Viktorsson, Kristina; Lewensohn, Rolf] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Viktorsson, Kristina; Lewensohn, Rolf] Karolinska Univ Hosp, Stockholm, Sweden. [Spira, Jack] Karolinska Inst Sci Pk, Oncopeptides AB, Solna, Sweden. RP Chauhan, D (reprint author), Dana Farber Canc Inst, M561,450 Brookline Ave, Boston, MA 02215 USA. EM Dharminder_Chauhan@dfci.harvard.edu; Rolf.lewensohn@ki.se; Kenneth_Anderson@dfci.harvard.edu FU NIH [P50100707, CA078378]; Swedish Cancer Society, Swedish Research Council and Stockholm Cancer Society FX This investigation was supported by NIH grants P50100707 and CA078378 (to D. Chauhan and K. C. Anderson); Swedish Cancer Society, Swedish Research Council and Stockholm Cancer Society (to K. Viktorsson and R. Lewensohn). NR 47 TC 12 Z9 14 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 3019 EP 3031 DI 10.1158/1078-0432.CCR-12-3752 PG 13 WC Oncology SC Oncology GA 155FF UT WOS:000319732000026 PM 23584492 ER PT J AU Socinski, MA Goldman, J El-Hariry, I Koczywas, M Vukovic, V Horn, L Paschold, E Salgia, R West, H Sequist, LV Bonomi, P Brahmer, J Chen, LC Sandler, A Belani, CP Webb, T Harper, H Huberman, M Ramalingam, S Wong, KK Teofilovici, F Guo, W Shapiro, GI AF Socinski, Mark A. Goldman, Jonathan El-Hariry, Iman Koczywas, Marianna Vukovic, Vojo Horn, Leora Paschold, Eugene Salgia, Ravi West, Howard Sequist, Lecia V. Bonomi, Philip Brahmer, Julie Chen, Lin-Chi Sandler, Alan Belani, Chandra P. Webb, Timothy Harper, Harry Huberman, Mark Ramalingam, Suresh Wong, Kwok-Kin Teofilovici, Florentina Guo, Wei Shapiro, Geoffrey I. TI A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID POTENT ANTITUMOR-ACTIVITY; HSP90 INHIBITOR; B-RAF; ANAPLASTIC LYMPHOMA; KINASE INHIBITORS; FUSION ONCOGENE; ALK; EML4-ALK; RESISTANCE; CHAPERONE AB Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non-small cell lung cancer (NSCLC). Experimental Design: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n 1) or PCR-based assays (n = 3), in crizotinib-naive patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia. Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement. C1 [Socinski, Mark A.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA. [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Goldman, Jonathan] Premiere Oncol, Santa Monica, CA USA. [Koczywas, Marianna] City Hope Natl Med Ctr, Duarte, CA USA. [El-Hariry, Iman; Vukovic, Vojo; Teofilovici, Florentina; Guo, Wei] Synta Pharmaceut Corp, Lexington, KY USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huberman, Mark] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wong, Kwok-Kin; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Paschold, Eugene] Piedmont Hematol Oncol Associates, Winston Salem, NC USA. [Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Bonomi, Philip] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [West, Howard] Swedish Canc Ctr, Seattle, WA USA. [Brahmer, Julie] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Chen, Lin-Chi] Nevada Canc Inst, Las Vegas, NV USA. [Sandler, Alan] Knight Canc Inst, OHSU, Portland, OR USA. [Webb, Timothy] Genesis Canc Ctr, Hot Springs, AR USA. [Harper, Harry] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Ramalingam, Suresh] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RP Socinski, MA (reprint author), Univ Pittsburgh, UPMC Canc Pavil, 5150 Ctr Ave,5th Floor, Pittsburgh, PA 15232 USA. EM socinskima@upmc.edu; geoffrey_shapiro@dfci.harvard.edu OI Belani, Chandra/0000-0001-5049-5329; wong, kwok kin/0000-0001-6323-235X FU Synta Pharmaceuticals; Dana-Farber/Harvard Cancer Center Specialized Program for Research Excellence (SPORE) in Lung Cancer NIH [P50 CA90578] FX This study was supported by Synta Pharmaceuticals. K.-K. Wong and G.I. Shapiro were also supported by the Dana-Farber/Harvard Cancer Center Specialized Program for Research Excellence (SPORE) in Lung Cancer NIH grant (P50 CA90578). NR 49 TC 103 Z9 106 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 3068 EP 3077 DI 10.1158/1078-0432.CCR-12-3381 PG 10 WC Oncology SC Oncology GA 155FF UT WOS:000319732000031 PM 23553849 ER PT J AU LoRusso, P Janne, PA Oliveira, M Rizvi, N Malburg, L Keedy, V Yee, L Copigneaux, C Hettmann, T Wu, CY Ang, A Halim, AB Beckman, RA Beaupre, D Berlin, J AF LoRusso, Patricia Jaenne, Pasi A. Oliveira, Moacyr Rizvi, Naiyer Malburg, Lisa Keedy, Vicki Yee, Lorrin Copigneaux, Catherine Hettmann, Thore Wu, Chi-Yuan Ang, Agnes Halim, Abdel-Baset Beckman, Robert A. Beaupre, Darrin Berlin, Jordan TI Phase I Study of U3-1287, a Fully Human Anti-HER3 Monoclonal Antibody, in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE; BREAST-CANCER; RECEPTOR INTERACTIONS; SIGNALING NETWORK; OVARIAN-CANCER; MESSENGER-RNA; THERAPY; HER3 AB Purpose: HER3 is a key dimerization partner for other HER family members, and its expression is associated with poor prognosis. This first-in-human study of U3-1287 (NCT00730470), a fully human anti-HER3 monoclonal antibody, evaluated its safety, tolerability, and pharmacokinetics in patients with advanced solid tumor. Experimental Design: The study was conducted in 2 parts: part 1-sequential cohorts received escalating doses (0.3-20 mg/kg) of U3-1287 every 2 weeks, starting 3 weeks after the first dose; part 2-additional patients received 9, 14, or 20 mg/kg U3-1287 every 2 weeks, based on observed tolerability and pharmacokinetics from part 1. Recommended phase II dose, adverse event rates, pharmacokinetics, and tumor response were determined. Results: Fifty-seven patients (part 1: 26; part 2: 31) received U3-1287. As no dose-limiting toxicities were reported, the maximum-tolerated dose was not reached. The maximum-administered dose was 20 mg/kg every 2 weeks. The most frequent adverse events related to U3-1287 were fatigue (21.1%), diarrhea (12.3%), nausea (10.5%), decreased appetite (7.0%), and dysgeusia (5.3%). No patient developed anti-U3-1287 antibodies. In these heavily pretreated patients, stable disease was maintained 9 weeks or more in 19.2% in part 1 and 10 weeks or more in 25.8% in part 2. Conclusion: U3-1287 treatment was well tolerated, and some evidence of disease stabilization was observed. Pharmacokinetic data support U3-1287 dosing of 9 to 20 mg/kg every 2 to 3 weeks. Combination studies of U3-1287 are ongoing. C1 [LoRusso, Patricia; Malburg, Lisa] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oliveira, Moacyr] Northwest Med Specialties, Tacoma, WA USA. [Yee, Lorrin] Vista Oncol, Olympia, WA USA. [Rizvi, Naiyer] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Keedy, Vicki; Berlin, Jordan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Copigneaux, Catherine; Halim, Abdel-Baset; Beckman, Robert A.] Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Hettmann, Thore] U3 Pharma GmbH, Munich, Germany. [Wu, Chi-Yuan; Ang, Agnes; Beaupre, Darrin] Amgen Inc, Thousand Oaks, CA 91320 USA. RP LoRusso, P (reprint author), Karmanos Canc Inst, 4100 John R St, Detroit, MI 48201 USA. EM lorussop@karmanos.org FU Daiichi Sankyo Pharmaceutical Development and Amgen, Inc.; U3 Pharma; Amgen and Daiichi Sankyo Pharmaceutical FX This study was sponsored by Daiichi Sankyo Pharmaceutical Development and Amgen, Inc. Funding for medical writing support was provided by Daiichi Sankyo.; P.M. LoRusso has a commercial research grant from U3 Pharma. P.A. Janne is a consultant/advisory board member of Amgen, Boehringer Ingelheim, Roche, Pfizer, Astra Zeneca, Clovis Oncology, and Lab Corp. V.L. Keedy has other commercial research support from Amgen and Daiichi Sankyo Pharmaceutical. L. Yee is a consultant/advisory board member of Dendreon, Spectrum Pharmaceutical, and Sanofi Aventis. C. Copigneaux is employed (other than primary affiliation; e.g., consulting) as a director (clinical development) at Daiichi Sankyo. A. Ang has ownership interest (including patents) in Amgen Inc. R.A. Beckman is employed (other than primary affiliation; e.g., consulting) as Chief ScientificOfficer of Onco-Mind, LLC.J. Berlin is a consultant/advisory board member of Amgen. No potential conflicts of interest were disclosed by the other authors. NR 36 TC 45 Z9 46 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 3078 EP 3087 DI 10.1158/1078-0432.CCR-12-3051 PG 10 WC Oncology SC Oncology GA 155FF UT WOS:000319732000032 PM 23591447 ER PT J AU Lee, RJ Saylor, PJ Michaelson, MD Rothenberg, SM Smas, ME Miyamoto, DT Gurski, CA Xie, WL Maheswaran, S Haber, DA Goldin, JG Smith, MR AF Lee, Richard J. Saylor, Philip J. Michaelson, M. Dror Rothenberg, S. Michael Smas, Malgorzata E. Miyamoto, David T. Gurski, Carol A. Xie, Wanling Maheswaran, Shyamala Haber, Daniel A. Goldin, Jonathan G. Smith, Matthew R. TI A Dose-Ranging Study of Cabozantinib in Men with Castration-Resistant Prostate Cancer and Bone Metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II; C-MET; CLINICAL-TRIALS; END-POINTS; EXPRESSION; RECEPTOR; INHIBITION; PREDNISONE; SUNITINIB AB Background: Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study of cabozantinib (100 mg daily) showed improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AE) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses. Experimental Design: An adaptive design was used to determine the lowest active daily dose among 60, 40, and 20 mg. The primary endpoint was week 6 bone scan response, defined as >= 30% decrease in bone scan lesion area. The secondary endpoint was change in circulating tumor cells (CTC). Results: Among 11 evaluable subjects enrolled at 40 mg, there were 9 partial responses (PR), 1 complete response, and 1 stable disease (SD). Of 10 subjects subsequently enrolled at 20 mg, there were 1 PR, 5 SDs, and 4 with progressive disease. Among 13 subjects enrolled on the 40mgexpansion cohort, there were 6 PRs and 7 SDs. No subjects required dose reduction or treatment interruption at 6 or 12 weeks; 3 subjects at dose level 0 discontinued due to AEs by 12 weeks. At 40 mg, median treatment duration was 27 weeks. 58% of subjects with >= 5 CTCs/7.5mL at baseline converted to <5. Conclusions: Cabozantinib 40 mg daily was associated with a high rate of bone scan response. Cabozantinib 40 mg daily was associated with better tolerability than previously reported for cabozantinib 100 mg daily. These observations informed the design of phase III studies of cabozantinib in mCRPC. C1 [Lee, Richard J.; Saylor, Philip J.; Michaelson, M. Dror; Rothenberg, S. Michael; Smas, Malgorzata E.; Miyamoto, David T.; Gurski, Carol A.; Maheswaran, Shyamala; Haber, Daniel A.; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Xie, Wanling] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldin, Jonathan G.] Univ Calif Los Angeles, Ctr Comp Vis & Imaging Biomarkers, Los Angeles, CA USA. RP Lee, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7018, Boston, MA 02114 USA. EM rjlee@partners.org OI Michaelson, Dror/0000-0001-9249-6338 FU Exelixis, Inc.; South San Francisco, CA; Department of Defense Prostate Cancer Research Program [W81XWH-09-1-0471]; Conquer Cancer Foundation; NIH [5K24CA121990]; Prostate Cancer Foundation FX This study was supported by Exelixis, Inc., South San Francisco, CA; by the Department of Defense Prostate Cancer Research Program (Award W81XWH-09-1-0471 to R.J. Lee); the Conquer Cancer Foundation (Career Development Award to R.J. Lee); the NIH [Midcareer Investigator Award No. 5K24CA121990 to M.R. Smith]; and competitive research awards from the Prostate Cancer Foundation. NR 26 TC 40 Z9 42 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2013 VL 19 IS 11 BP 3088 EP 3094 DI 10.1158/1078-0432.CCR-13-0319 PG 7 WC Oncology SC Oncology GA 155FF UT WOS:000319732000033 PM 23553848 ER PT J AU Young, B AF Young, Bessie TI Geography and ESRD Care: What Contributes Most to Hemodialysis Patient-Provider Visit Variation? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CLINICAL-PERFORMANCE TARGETS; STAGE RENAL-DISEASE; REGIONAL-VARIATIONS; PHYSICIAN CONTACT; OUTCOMES; FREQUENCY; QUALITY C1 [Young, Bessie] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Kidney Res Inst, Div Nephrol, Seattle, WA 98195 USA. RP Young, B (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 111-A RDU,1660 S Columbian Way, Seattle, WA 98108 USA. EM youngb@u.washington.edu NR 20 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2013 VL 8 IS 6 BP 898 EP 900 DI 10.2215/CJN.03970413 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 160VZ UT WOS:000320149900003 PM 23749447 ER PT J AU Isakova, T Barchi-Chung, A Enfield, G Smith, K Vargas, G Houston, J Xie, HL Wahl, P Schiavenato, E Dosch, A Gutierrez, OM Diego, J Lenz, O Contreras, G Mendez, A Weiner, RB Wolf, M AF Isakova, Tamara Barchi-Chung, Allison Enfield, Gwen Smith, Kelsey Vargas, Gabriella Houston, Jessica Xie, Huiliang Wahl, Patricia Schiavenato, Eva Dosch, Austin Gutierrez, Orlando M. Diego, Jorge Lenz, Oliver Contreras, Gabriel Mendez, Armando Weiner, Rory B. Wolf, Myles TI Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GROWTH-FACTOR 23; CARDIOVASCULAR EVENTS; PARATHYROID-HORMONE; PHOSPHORUS; FGF-23; MEN; INITIATION; DIALYSIS; CALCIUM AB Background Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited. Design, setting, participants, & measurements In this 2 X 2 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline. Results Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet X time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC X time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet X LC X time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. Conclusion The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3-4 and normal serum phosphate levels. C1 [Isakova, Tamara; Barchi-Chung, Allison; Smith, Kelsey; Vargas, Gabriella; Houston, Jessica; Wahl, Patricia; Schiavenato, Eva; Dosch, Austin; Diego, Jorge; Lenz, Oliver; Contreras, Gabriel; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Enfield, Gwen] Univ Miami, Miller Sch Med, Clin Res Ctr, Miami, FL 33136 USA. [Xie, Huiliang] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Mendez, Armando] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Diabet Res Inst, Miami, FL 33136 USA. [Gutierrez, Orlando M.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Weiner, Rory B.] Massachusetts Gen Hosp, Dept Med, Cardiol Unit, Boston, MA 02114 USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, 1120 NW 14th St,CRB 819, Miami, FL 33136 USA. EM mwolf2@med.miami.edu RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 FU Shire Pharmaceuticals; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK087858, R01DK076116, R01DK081374]; University of Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences [1UL1TR000460]; National Institute on Minority Health and Health Disparities FX This study was supported by a grant from Shire Pharmaceuticals and by grants from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases: K23DK087858 (T.I.), R01DK076116 (M.W.) and R01DK081374 (M.W.).; The project described was supported by grant no. 1UL1TR000460, University of Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 19 TC 36 Z9 39 U1 0 U2 32 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2013 VL 8 IS 6 BP 1009 EP 1018 DI 10.2215/CJN.09250912 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 160VZ UT WOS:000320149900018 PM 23471131 ER PT J AU Hoenig, MP Shapiro, E Hladik, GA AF Hoenig, Melanie P. Shapiro, Evelyn Hladik, Gerald A. TI Lessons Learned from the ASN Renal Educator Listserv and Survey SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MEDICAL-EDUCATION; CURRICULUM; STUDENTS AB Nephrology ranks next to last in career choices among US medical school graduates. The American Society of Nephrology established a Workforce Committee to help address this issue. Surveys of US medical students indicate that experiences during kidney pathophysiology courses in the preclerkship years may impact their decision to consider a career in nephrology. In October of 2011, preclinical kidney physiology and pathophysiology course directors at US medical schools were surveyed about teaching methods, curricular content, resources, and institutional support for teaching to identify what worked well and what impairs their teaching efforts. A Listserv of these educators, the American Society of Nephrology Renal Educators Listserv, was used to electronically administer the survey. Course leaders from 62 of 114 (54.4%) surveyed medical schools responded. Most of these educators are nephrologists, but physiologists and other clinicians also lead courses; 60% of course directors noted that lectures are videotaped, resulting in decreased attendance. A range of resources is used: 68% use audience response systems, 16% use the simulation center, and none of the educators indicated use of social media (such as Twitter or Facehook); 50% of respondents receive no remuneration, and 68% receive no full-time equivalent for their efforts. Audience response systems, virtual microscopy, and flash animations were identified as valuable teaching tools. Course directors, during subsequent dialogue on the American Society of Nephrology Renal Educators Listserv, have cited incorporation of case scenarios and integration of clinical exposure during preclinical years as methods that inspired interest. Hopefully, adoption of such approaches will ultimately serve to stimulate interest in nephrology. C1 [Hoenig, Melanie P.] Joslin Clin, Div Nephrol, Boston, MA 02215 USA. [Hoenig, Melanie P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hoenig, Melanie P.] Harvard Univ, Sch Med, Boston, MA USA. [Shapiro, Evelyn] Amer Soc Nephrol, Washington, DC USA. [Hladik, Gerald A.] Univ N Carolina, Sch Med, Div Nephrol, Chapel Hill, NC USA. [Hladik, Gerald A.] Univ N Carolina, Kidney Ctr, Chapel Hill, NC USA. RP Hoenig, MP (reprint author), Joslin Clin, Renal Unit, Boston, MA 02215 USA. EM Melanie.Hoenig@joslin.harvard.edu NR 36 TC 8 Z9 8 U1 1 U2 6 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 JUN PY 2013 VL 8 IS 6 BP 1054 EP 160 DI 10.2215/CJN.07410712 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 160VZ UT WOS:000320149900024 PM 23293124 ER PT J AU Runz, H AF Runz, Heiko TI Lipids: new biology and therapeutic targets revealed through human genetics SO CLINICAL LIPIDOLOGY LA English DT Editorial Material ID PATHWAYS AB This year's Deuel Conference on Lipids focused on the seminal contribution of human genetics to lipid biology and disease. Named in honor of Harry J Deuel Jr, famous single author of the three-volume textbook The Lipids (Interscience Publishers Inc., NY, USA) and established in 1955, the Deuel Conference is considered the longest-standing annual meeting on lipid metabolism in the USA. The 2013 meeting took place at the Silverado Resort of Napa Valley (CA, USA) and was characterized by first-rank scientific contributions and discussions in a friendly and informal setting. Four scientific sessions over 2 and a half days, a poster session and generous breaks allowed for stimulating scientific, as well as social interactions of scientists from academia and industry alike. C1 [Runz, Heiko] Heidelberg Univ, Inst Human Genet, Mol Med Partnership Unit, D-69120 Heidelberg, Germany. [Runz, Heiko] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Runz, H (reprint author), Heidelberg Univ, Inst Human Genet, Mol Med Partnership Unit, INF 350, D-69120 Heidelberg, Germany. EM heiko.runz@med.uni-heidelberg.de NR 15 TC 0 Z9 0 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 J9 CLIN LIPIDOL JI Clin. Lipidol. PD JUN PY 2013 VL 8 IS 3 BP 295 EP 298 DI 10.2217/CLP.13.22 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 158KX UT WOS:000319970500011 ER PT J AU Magidson, JF Wang, S Lejuez, CW Iza, M Blanco, C AF Magidson, Jessica F. Wang, Shuai Lejuez, C. W. Iza, Miren Blanco, Carlos TI PROSPECTIVE STUDY OF SUBSTANCE-INDUCED AND INDEPENDENT MAJOR DEPRESSIVE DISORDER AMONG INDIVIDUALS WITH SUBSTANCE USE DISORDERS IN A NATIONALLY REPRESENTATIVE SAMPLE SO DEPRESSION AND ANXIETY LA English DT Article DE major depressive disorder; substance-related disorder; classification; epidemiology; substance use ID PSYCHIATRIC RESEARCH INTERVIEW; ALCOHOL-USE DISORDER; EPIDEMIOLOGIC SURVEY; ANXIETY DISORDERS; DEPENDENT PATIENTS; MENTAL-DISORDERS; DSM-IV; RELIABILITY; MOOD; COMORBIDITY AB Background Depression and substance use disorders (SUDs) commonly co-occur, which presents diagnostic challenges in classifying independent major depressive disorder (MDD) versus substance-induced depressive disorder (SIDD). It remains unclear if distinct characteristics and/or patterns in temporal course distinguish MDD-SUD and SIDD to guide these decisions. Further, evidence suggests that a significant portion of individuals with SIDD are later reclassified as having independent MDD. Continued research to improve our understanding of differences between these two and changes in reclassification over time is necessary for diagnostic clarification and to guide clinical decisions when treating depression in the context of SUDs. Methods The current study compared individuals with MDD-SUD versus SIDD at baseline and examined reclassification of DSM-IV Axis I diagnoses over a 3-year follow up in a large, nationally representative epidemiological sample (n = 2,121). Results Findings demonstrated that SIDD was extremely rare at both time points. At baseline, individuals with SIDD were more likely to be non-White, have less education, less likely to have insurance, less likely to have dysthymia or alcohol abuse, and more likely to have drug dependence compared to those with independent MDD. Of individuals with SIDD at Wave 1 who had a depressive episode between Waves 1 and 2, the overwhelming majority (>95%) had an independent MDD, not SIDD, episode. There were no significant group differences in the incidence of other mood disorders or SUDs at Wave 2. Conclusions Findings have important etiological and treatment implications for the classification and treatment of depression in the context of SUDs. (C) 2013 Wiley Periodicals, Inc. C1 [Magidson, Jessica F.; Lejuez, C. W.] Univ Maryland, College Pk, MD 20742 USA. [Magidson, Jessica F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wang, Shuai; Iza, Miren; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. RP Magidson, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM jmagidson@partners.org RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU National Institute on Alcohol Abuse and Alcoholism; NIH [DA019606, DA020783, DA023200, DA023973, MH082773, R36DA034513]; New York State Psychiatric Institute FX The National Epidemiologic Survey on alcohol and related conditions was sponsored by the National Institute on Alcohol Abuse and Alcoholism with supplemental support from the National Institute on Drug Abuse. Work on this manuscript was supported by NIH grants DA019606, DA020783, DA023200, DA023973, and MH082773 (Blanco), R36DA034513 (Magidson), and the New York State Psychiatric Institute (Blanco). NR 25 TC 6 Z9 6 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2013 VL 30 IS 6 BP 538 EP 545 DI 10.1002/da.22122 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 157CC UT WOS:000319872200005 PM 23649540 ER PT J AU Olson, J Kalina, C Berg, D AF Olson, Jonathan Kalina, Carol Berg, Daniel TI Foam Dressing as a Suturing Model SO DERMATOLOGIC SURGERY LA English DT Letter ID FLAP MECHANICS C1 [Olson, Jonathan; Berg, Daniel] Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA. [Kalina, Carol] Vet Affairs Puget Sound Healthcare Syst, Dermatol Sect, Seattle, WA USA. RP Olson, J (reprint author), Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA. NR 5 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JUN PY 2013 VL 39 IS 6 BP 952 EP 953 DI 10.1111/dsu.12169 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA 157ST UT WOS:000319920100020 PM 23464974 ER PT J AU Spiegelman, BM AF Spiegelman, Bruce M. TI Banting Lecture 2012 Regulation of Adipogenesis: Toward New Therapeutics for Metabolic Disease SO DIABETES LA English DT Article ID BROWN ADIPOSE-TISSUE; COACTIVATOR; MUSCLE; FAT; THERMOGENESIS; ADIPOCYTES; DISTINCT; PRDM16; DRIVES; BEIGE AB The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Bruce M. Spiegelman, PhD, of Harvard Medical School and the Dana-Farber Cancer Institute in Boston, received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 72nd Scientific Sessions, 8-12 June 2012, Philadelphia, Pennsylvania. He presented the Banting Lecture, "Transcriptional Control of Adipogenesis Toward a New Generation of Therapeutics for Metabolic Disease," on Sunday, 10 June 2012. In his lecture, Dr. Spiegelman described the discovery of several transcriptional components that control adipose cell development: PPAR-gamma, PGC1-alpha, and PRDM16. He also described the cloning and characterization of beige fat cells, the thermogenic "brown-like" cells that can develop in white fat depots. Lastly, Dr. Spiegelman discussed irisin, a newly discovered regulatory hormone that converts white fat into the more thermogenic beige fat. Dr. Spiegelman's research has found that irisin, which is induced by exercise, appears to activate some of the same health benefits as exercise, including improvement of glycemic control. Understanding the regulation of adipose tissue, white, brown, and beige, can potentially lead to the development of a new generation of therapeutics for diabetes prevention and treatment. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU National Institutes of Health (the National Institute of Diabetes and Digestive and Kidney Diseases specifically); JPB Foundation FX This work has been funded by the National Institutes of Health (the National Institute of Diabetes and Digestive and Kidney Diseases specifically) and by The JPB Foundation. NR 17 TC 52 Z9 62 U1 3 U2 30 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2013 VL 62 IS 6 BP 1774 EP 1782 DI 10.2337/db12-1665 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 156SU UT WOS:000319845000001 PM 23704518 ER PT J AU Sacks, H Symonds, ME AF Sacks, Harold Symonds, Michael E. TI Anatomical Locations of Human trovvn Adipose Tissue Functional Relevance and Implications in Obesity and Type 2 Diabetes SO DIABETES LA English DT Article ID BROWN ADIPOSE; ADULT HUMANS; SKIN TEMPERATURE; ENERGY-BALANCE; GLUCOSE-UPTAKE; COLD-EXPOSURE; FAT; THERMOGENESIS; AGE; IDENTIFICATION AB We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms. C1 [Sacks, Harold] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90095 USA. [Symonds, Michael E.] Univ Nottingham, Early Life Nutr Res Unit, Acad Div Child Hlth, Sch Clin Sci,Univ Hosp, Nottingham NG7 2RD, England. RP Sacks, H (reprint author), VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90095 USA. EM hsacks@hotmail.com OI Symonds, Michael/0000-0001-9649-8963 NR 50 TC 45 Z9 46 U1 0 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2013 VL 62 IS 6 BP 1783 EP 1790 DI 10.2337/db12-1430 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 156SU UT WOS:000319845000002 PM 23704519 ER PT J AU Kelly, JF Hoeppner, BB AF Kelly, John F. Hoeppner, Bettina B. TI Does Alcoholics Anonymous work differently for men and women? A moderated multiple-mediation analysis in a large clinical sample SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcoholics Anonymous; Gender; Recovery; Addiction treatment; 12-Step; Women ID GENDER-DIFFERENCES; BEHAVIOR-CHANGE; SOCIAL ROLES; INDUSTRIALIZED COUNTRIES; PROJECT MATCH; MECHANISMS; DEPRESSION; PARTICIPATION; OUTCOMES; ASSOCIATION AB Background: Alcoholics Anonymous (AA) began as a male organization, but about one third is now female. Studies have found that women participate at least as much as men and benefit equally from AA, but it is unclear whether women benefit from AA in the same or different ways as men. This study tested whether gender moderated the mechanisms through which AA aids recovery. Methods: A cohort study of alcohol dependent adults (N = 1726; 24% female; Project MATCH) was assessed on AA attendance during treatment; with mediators at 9 months; outcomes (Percent Days Abstinent [PDA] and Drinks per Drinking Day [DDD]) at 15 months. Multiple mediator models tested whether purported mechanisms (i.e., self-efficacy, depression, social networks, spirituality/religiosity) explained AA's effects differently for men and women controlling for baseline values, mediators, treatment, and other confounders. Results: For PDA, the proportion of AA's effect accounted for by the mediators was similar for men (53%) and women (49%). Both men and women were found to benefit from changes in social factors but these mechanisms were more important among men. For DDD, the mediators accounted for 70% of the effect of AA for men and 41% for women. Again, men benefitted mostly from social changes. Independent of AA's effects, negative affect self-efficacy was shown to have a strong relationship to outcome for women but not men. Conclusions: The recovery benefits derived from AA differ in nature and magnitude between men and women and may reflect differing needs based on recovery challenges related to gender-based social roles and drinking contexts. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [R21 AA016762]; National Institute on Drug Abuse [K01 DA027097] FX This research was supported by a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA, R21 AA016762; Mechanisms and Moderators of Behavior Change in Alcoholics Anonymous) and a grant from the National Institute on Drug Abuse (K01 DA027097). NIAAA and NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 59 TC 3 Z9 4 U1 2 U2 26 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 JUN 1 PY 2013 VL 130 IS 1-3 BP 186 EP 193 DI 10.1016/j.drugalcdep.2012.11.005 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 154ZK UT WOS:000319715000024 PM 23206376 ER PT J AU McKenna, JT Kocsis, B McCarley, RW AF McKenna, James T. Kocsis, Bernat McCarley, Robert W. TI Aberrant cortical neuroplasticity in the OSA patient (Commentary on Opie et al.) SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article ID THETA-BURST STIMULATION; OBSTRUCTIVE SLEEP-APNEA; CORTEX C1 [McKenna, James T.; McCarley, Robert W.] Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA. [Kocsis, Bernat] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Psychiat, Sch Med, Boston, MA 02215 USA. RP McKenna, JT (reprint author), Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 NR 8 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2013 VL 37 IS 11 BP 1843 EP 1843 DI 10.1111/ejn.12221 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 156PK UT WOS:000319834600012 PM 23725099 ER PT J AU Farhat, MR Loring, SH Riskind, P Weinhouse, G AF Farhat, Maha R. Loring, Stephen H. Riskind, Peter Weinhouse, Gerald TI Disturbance of respiratory muscle control in a patient with early-stage multiple sclerosis SO EUROPEAN RESPIRATORY JOURNAL LA English DT Letter ID DYSFUNCTION; INVOLVEMENT C1 [Farhat, Maha R.] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. [Loring, Stephen H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anaesthesia & Crit Care, Boston, MA 02215 USA. [Riskind, Peter] Univ Massachusetts, Mem Hosp, Dept Neurol, Worcester, MA 01605 USA. [Weinhouse, Gerald] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pulm & Crit Care, Boston, MA USA. RP Farhat, MR (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM mrfarhat@partners.org OI Farhat, Maha/0000-0002-3871-5760 NR 10 TC 1 Z9 1 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUN PY 2013 VL 41 IS 6 BP 1454 EP 1456 DI 10.1183/09031936.00172312 PG 3 WC Respiratory System SC Respiratory System GA 161RT UT WOS:000320211700030 PM 23728406 ER PT J AU Rinne, ML Lee, EQ Nayak, L Norden, AD Beroukhim, R Wen, PY Reardon, DA AF Rinne, Mikael L. Lee, Eudocia Q. Nayak, Lakshmi Norden, Andrew D. Beroukhim, Rameen Wen, Patrick Y. Reardon, David A. TI Update on bevacizumab and other angiogenesis inhibitors for brain cancer SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE angiogenesis; brain metastases; glioblastoma; malignant glioma; vascular endothelial growth factor ID PHASE-II TRIAL; RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; ENDOTHELIAL GROWTH-FACTOR; NERVOUS-SYSTEM METASTASES; TYROSINE KINASE INHIBITOR; PROGRESSION-FREE SURVIVAL; SINGLE-AGENT BEVACIZUMAB; INTEGRATED GENOMIC ANALYSIS AB Introduction: Primary and metastatic brain tumors remain a major challenge. The most common primary adult malignant brain tumor, glioblastoma (GBM), confers a dismal prognosis as does the development of CNS metastases for most systemic malignancies. Anti-angiogenic therapy has been a major clinical research focus in neuro-oncology over the past 5 years. Areas covered: Culmination of this work includes US FDA accelerated approval of bevacizumab for recurrent GBM and the completion of two placebo-controlled Phase III studies of bevacizumab for newly diagnosed GBM. A multitude of anti-angiogenics are in evaluation for neurooncology patients but none has thus far surpassed the therapeutic benefit of bevacizumab. Expert opinion: These agents demonstrate adequate safety and the majority of GBM patients derive benefit. Furthermore, their anti-permeability effect can substantially decrease tumor-associated edema leading to stable or improved neurologic function and quality of life. In particular, anti-angiogenics significantly prolong progression-free survival-a noteworthy achievement in the context of infiltrative and destructive brain tumors like GBM; however, in a manner analogous to other cancers, their impact on overall survival for GBM patients is modest at best. Despite substantial clinical research efforts, many fundamental questions regarding anti-angiogenic agents in brain tumor patients remain unanswered. C1 [Rinne, Mikael L.; Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Beroukhim, Rameen; Wen, Patrick Y.; Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Rinne, Mikael L.; Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Beroukhim, Rameen; Reardon, David A.] Brigham & Womens Hosp, Ctr Neurooncol, Dept Med Oncol, Boston, MA 02215 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW460F, Boston, MA 02115 USA. EM david_reardon@dfci.harvard.edu FU Merck/Schering-Plough; Roche/Genentech; Merck KGaA/EMD Serono (G) FX DA Reardon has received financial compensation as a consultant for Merck/Schering-Plough, Roche/Genentech, and Merck KGaA/EMD Serono (G). He is a member of the speakers' bureau for Merck/Schering-Plough and Roche/Genentech. R Beroukhim has received financial compensation as a consultant for Novartis. P Wen has received funds or other from Amgen, Astra Zeneca, Exelixis, Eisai, Genentech, Merck, Novartis, Medimmune, Sanofi Aventis, Vascular Biogenics and Stemline. E Lee is a member of the advisory board to Novartis. NR 172 TC 17 Z9 18 U1 3 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 EI 1744-7623 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD JUN PY 2013 VL 18 IS 2 BP 137 EP 153 DI 10.1517/14728214.2013.794784 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156QM UT WOS:000319837500003 PM 23668489 ER PT J AU Tecilazich, F Dinh, TL Veves, A AF Tecilazich, Francesco Dinh, Thanh L. Veves, Aristidis TI Emerging drugs for the treatment of diabetic ulcers SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE diabetes; foot ulceration; growth factors; new treatments ID ENDOTHELIAL PROGENITOR CELLS; PROTEIN-TYROSINE PHOSPHATASES; RANDOMIZED CLINICAL-TRIAL; FIBROBLAST-GROWTH-FACTOR; PLATELET-RICH PLASMA; SMOOTH-MUSCLE-CELLS; SHOCK-WAVE THERAPY; FOOT ULCERS; SUBSTANCE-P; NEUROPEPTIDE-Y AB Introduction: Diabetic ulcers are chronic nonhealing ulcerations that despite the available medical tools still result in high amputation rates. Growing evidence suggests that alteration of the biochemical milieu of the chronic wound plays a significant role in impaired diabetic wound healing. Areas covered: The basic pathophysiology and the conventional treatment strategy of diabetic foot ulcers have been reviewed in the first section. In the second part, the most up-to-date bench and translational research in the field are described. The third section focuses on the drugs currently under development and the ongoing clinical trials evaluating their safety and efficacy. Finally, the major drug development issues and the possible scientific approaches to overcome them are analyzed. Expert opinion: Significant strides in understanding the chronic wound development have led to the development of topical therapies to address aberrant expression of growth factors and overexpression of inflammatory cytokines. Current research in the laboratory suggests that while decreased growth factor expression occurs at the local wound level, increased systemic serum levels of growth factors suggest growth factor resistance. C1 [Tecilazich, Francesco; Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. [Tecilazich, Francesco; Veves, Aristidis] Beth Israel Deaconess Foot Ctr, Microcirculat Lab, Boston, MA USA. [Dinh, Thanh L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Podiatry, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu FU National Institutes of Health [R01-NS046710, R01-DK076937, R01 NS066205] FX This work was supported by National Institutes of Health Grants R01-NS046710, R01-DK076937 and R01 NS066205 to Aristidis Veves. All authors state no conflict of interest. NR 102 TC 3 Z9 5 U1 2 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD JUN PY 2013 VL 18 IS 2 BP 207 EP 217 DI 10.1517/14728214.2013.802305 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156QM UT WOS:000319837500007 PM 23687931 ER PT J AU Correll, M Johnson, CK Ferrari, G Brizzio, M Mak, AWC Quackenbush, J Shaw, RE Zapolanski, A Grau, JB AF Correll, Mick Johnson, Christopher K. Ferrari, Giovanni Brizzio, Mariano Mak, Andrew W. C. Quackenbush, John Shaw, Richard E. Zapolanski, Alex Grau, Juan B. TI Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting SO GENOMICS LA English DT Article DE Cardiovascular surgery; Ultra-high throughput sequencing; Gene polymorphisms; Platelets ID CARDIOVASCULAR OUTCOMES; ANTIPLATELET THERAPY; HEART-ASSOCIATION; CYP2C19 GENOTYPE; TASK-FORCE; REACTIVITY; INTERVENTION; RESPONSIVENESS; POLYMORPHISMS; INHIBITION AB Clopidogrel is an oral antiplatelet pro-drug prescribed to 40 million patients worldwide who are at risk for thrombotic events or receiving percutaneous coronary intervention (PCI). However about a fifth of patients treated with clopidogrel do not respond adequately to the drug. From a cohort of 105 patients on whom we had functional data on clopidogrel response, we used ultra-high throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to respond. Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predicted if a patient would respond to clopidogrel 52.4% of the time. Similarly, testing of the ABCB1 gene only correctly foretold response in 51 (48.6%) patients. These results are clinically relevant and suggest that until additional genetic factors are discovered that predict response more completely, functional assays are more appropriate for clinical use. (C) 2013 Elsevier Inc. All rights reserved. C1 [Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA. [Johnson, Christopher K.; Ferrari, Giovanni; Brizzio, Mariano; Mak, Andrew W. C.; Quackenbush, John; Shaw, Richard E.; Zapolanski, Alex; Grau, Juan B.] Columbia Univ Coll Phys & Surg, Valley Columbia Heart Ctr, Ridgewood, NJ 07450 USA. [Ferrari, Giovanni; Grau, Juan B.] Univ Penn, Sch Med, Glenolden, PA 19036 USA. RP Grau, JB (reprint author), Valley Columbia Heart Ctr, 223 North Van Dien Ave, Ridgewood, NJ 07450 USA. EM jbg2136@columbia.edu OI Ferrari, Giovanni/0000-0002-8863-2496 FU NHLBI NIH HHS [P01 HL083069]; NLM NIH HHS [R01 LM010129] NR 25 TC 1 Z9 3 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2013 VL 101 IS 6 BP 313 EP 317 DI 10.1016/j.ygeno.2013.01.005 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 156SS UT WOS:000319844800001 PM 23462555 ER PT J AU Bentov, I Damodarasamy, M Plymate, S Reed, MJ AF Bentov, Itay Damodarasamy, Mamatha Plymate, Stephen Reed, May J. TI B16/F10 tumors in aged 3D collagen in vitro simulate tumor growth and gene expression in aged mice in vivo SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE Aged; Mice; Gene expression; B16/F10 melanoma tumors; 3D collagen ID HORMONE RECEPTOR; HUMAN-MELANOMA; CANCER; OLD; CELLS; GELS AB Although the incidence of cancer rises with age, tumor growth is often slowed in older hosts. The B16/F10 melanoma cell line is commonly used in murine models of age-related tumor growth suppression. We wished to determine if the growth pattern and gene expression of B16/10 tumors grown in aged mice could be simulated in 3D collagen matrices derived from aged mice. Outcome measures were tumor size in vitro and gene expression of the key growth regulatory molecules: growth hormone receptor (GHR), IL-10R beta, IL-4R alpha, and IL-6. B16/F10 tumors were grown in 20-25-mo-old C57/BL6 male mice. Tumor sizes ranged from 30 to 4,910 mg in vivo. Tumors from a subset of mice were removed after euthanasia, and equivalent amounts of each tumor were placed in aged 3D collagen and grown for 5 d. Tumor sizes in aged 3D collagen correlated highly with their original tumor size in vivo. Gene expression changes noted in vivo were also maintained during tumor growth in aged 3D collagen in vitro. The relative expression of GHR was increased, IL-10R beta was unchanged, and IL-4R alpha and IL-6 were decreased in the larger tumors relative to the smaller tumors in vitro, in a pattern similar to that noted in vivo. We propose that 3D matrices from aged mice provide an in vitro model of tumor growth that correlates highly with tumor size and expression of key regulatory molecules in vivo. C1 [Bentov, Itay] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA. [Damodarasamy, Mamatha; Plymate, Stephen; Reed, May J.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. [Plymate, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Reed, May J.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. RP Reed, MJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Box 359625,325 9th Ave, Seattle, WA 98104 USA. EM mjr@uw.edu FU [U54 CA126540]; [R01 AG015837]; [R21 AG033391] FX The authors thank Nathan Karres, Margaret Eugenio, and Matthew NR Johnson for assistance with the tumor samples. This work was supported by U54 CA126540, R01 AG015837, and R21 AG033391. NR 23 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUN PY 2013 VL 49 IS 6 BP 395 EP 399 DI 10.1007/s11626-013-9623-3 PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 162QG UT WOS:000320279500001 PM 23661088 ER PT J AU Rosenberg, AR Dussel, V Kang, T Geyer, JR Gerhardt, CA Feudtner, C Wolfe, J AF Rosenberg, Abby R. Dussel, Veronica Kang, Tammy Geyer, J. Russel Gerhardt, Cynthia A. Feudtner, Chris Wolfe, Joanne TI Psychological Distress in Parents of Children With Advanced Cancer SO JAMA PEDIATRICS LA English DT Article ID POSTTRAUMATIC STRESS SYMPTOMS; BEREAVED PARENTS; CHILDHOOD-CANCER; GENERAL-POPULATION; PEDIATRIC CANCER; SCREENING SCALES; MENTAL-HEALTH; ADJUSTMENT; FAMILY; ILLNESS AB Importance: Parent psychological distress can impact the well-being of childhood cancer patients and other children in the home. Recognizing and alleviating factors of parent distress may improve overall family survivorship experiences following childhood cancer. Objectives: To describe the prevalence and factors of psychological distress (PD) among parents of children with advanced cancer. Design: Cohort study embedded within a randomized clinical trial (Pediatric Quality of Life and Evaluation of Symptoms Technology [PediQUEST] study). Setting: Multicenter study conducted at 3 children's hospitals (Boston Children's Hospital, Children's Hospital of Philadelphia, and Seattle Children's Hospital). Participants: Parents of children with advanced (progressive, recurrent, or refractory) cancer. Main Outcome Measure: Parental PD, as measured by the Kessler-6 Psychological Distress Scale. Results: Eighty-six of 104 parents completed the Survey About Caring for Children With Cancer (83% par-ticipation); 81 parents had complete Kessler-6 Psychological Distress Scale data. More than 50% of parents reported high PD and 16% met criteria for serious PD (compared with US prevalence of 2%-3%). Parent perceptions of prognosis, goals of therapy, child symptoms/suffering, and financial hardship were associated with PD. In multivariate analyses, average parent Kessler-6 Psychological Distress Scale scores were higher among parents who believed their child was suffering highly and who reported great economic hardship. Conversely, PD was significantly lower among parents whose prognostic understanding was aligned with concrete goals of care. Conclusions and Relevance: Parenting a child with advanced cancer is strongly associated with high to severe levels of PD. Interventions aimed at aligning prognostic understanding with concrete care goals and easing child suffering and financial hardship may mitigate parental PD. C1 [Rosenberg, Abby R.; Geyer, J. Russel] Univ Washington, Seattle Childrens Hosp, Div Pediat Hematol Oncol, Seattle, WA 98195 USA. [Rosenberg, Abby R.; Geyer, J. Russel] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Rosenberg, Abby R.; Geyer, J. Russel] Univ Washington, Seattle, WA 98195 USA. [Dussel, Veronica; Wolfe, Joanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Wolfe, Joanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Kang, Tammy; Feudtner, Chris] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gerhardt, Cynthia A.] Ohio State Univ, Columbus, OH 43210 USA. [Gerhardt, Cynthia A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 450 Brookline Ave, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu RI Gerhardt, Cynthia/E-3109-2011 FU National Institutes of Health/National Cancer Institute [1K07 CA096746-01]; Charles H. Hood Foundation Child Health Research Award; American Cancer Society Pilot and Exploratory Project Award; Ruth L. Kirschstein National Research Service Award [T32CA009351] FX Funding/Support: This project was part of the Pedi-QUEST study and funded by National Institutes of Health/National Cancer Institute grant 1K07 CA096746-01, a Charles H. Hood Foundation Child Health Research Award, and an American Cancer Society Pilot and Exploratory Project Award in Palliative Care of Cancer Patients and Their Families. Dr Rosenberg was supported by Ruth L. Kirschstein National Research Service Award T32CA009351. NR 41 TC 22 Z9 23 U1 1 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 J9 JAMA PEDIATR JI JAMA Pediatr. PD JUN PY 2013 VL 167 IS 6 BP 537 EP 543 DI 10.1001/jamapediatrics.2013.628 PG 7 WC Pediatrics SC Pediatrics GA 156NR UT WOS:000319829700008 PM 23545569 ER PT J AU Duda, DG Munn, LL Jain, RK AF Duda, Dan G. Munn, Lance L. Jain, Rakesh K. TI Can We Identify Predictive Biomarkers for Antiangiogenic Therapy of Cancer Using Mathematical Modeling? SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III; BEVACIZUMAB; VEGF; ANGIOGENESIS; TRIALS; IMPACT; CELLS C1 [Duda, Dan G.; Munn, Lance L.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. [Duda, Dan G.; Munn, Lance L.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R01-CA115767, P01-CA080124, R01-CA085140, R01-CA126642, R01-CA149285, R01-CA159258, R21-CA139168] NR 24 TC 7 Z9 7 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUN PY 2013 VL 105 IS 11 BP 762 EP 765 DI 10.1093/jnci/djt114 PG 4 WC Oncology SC Oncology GA 160QK UT WOS:000320134100006 PM 23670727 ER PT J AU Soeteman, DI Stout, NK Ozanne, EM Greenberg, C Hassett, MJ Schrag, D Punglia, RS AF Soeteman, Djra I. Stout, Natasha K. Ozanne, Elissa M. Greenberg, Caprice Hassett, Michael J. Schrag, Deborah Punglia, Rinaa S. TI Modeling the Effectiveness of Initial Management Strategies for Ductal Carcinoma In Situ SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL ADJUVANT BREAST; LOCAL RECURRENCE; OLDER WOMEN; CANCER; RADIOTHERAPY; TAMOXIFEN; TRIAL; SURVIVAL; DIAGNOSIS; OUTCOMES AB The prevalence of ductal carcinoma in situ (DCIS) and the marked variability in patterns of care highlight the need for comparative effectiveness research. We sought to quantify the tradeoffs among alternative management strategies for DCIS with respect to disease outcomes and breast preservation. We developed a disease simulation model integrating data from the published literature to simulate the clinical events after six treatments (lumpectomy alone, lumpectomy with radiation, lumpectomy with radiation and tamoxifen, lumpectomy with tamoxifen, and mastectomy with and without breast reconstruction) for women with newly diagnosed DCIS. Outcomes included disease-free, invasive disease-free, and overall survival and breast preservation. For a cohort of 1 million simulated women aged 45 years at diagnosis, both mastectomy and lumpectomy with radiation and tamoxifen were associated with a 12-month improvement in overall survival relative to lumpectomy alone. Adding radiation therapy to lumpectomy resulted in a 6-month improvement in overall survival but decreased long-term breast-preservation outcomes (likelihood of lifetime breast preservation 0.781 vs 0.843 for lumpectomy alone). This decrement with radiation therapy was mitigated by the addition of tamoxifen (likelihood of lifetime breast preservation 0.846). Overall survival benefits of the six management strategies for DCIS are within 1 year, suggesting that treatment decisions can be informed by the patients preference for breast preservation and disutility for recurrence. Our delineation of personalized outcomes for each strategy can help patients understand the implications of their treatment choice, so their decisions may reflect their own personal values and help improve the quality of care for patients with DCIS. C1 [Soeteman, Djra I.] Harvard Univ, Ctr Hlth Decis Sci, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Stout, Natasha K.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Ozanne, Elissa M.] Univ Calif San Francisco, Dept Surg, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Greenberg, Caprice] Univ Wisconsin, Dept Surg, Madison, WI USA. [Hassett, Michael J.; Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Punglia, Rinaa S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Soeteman, DI (reprint author), Harvard Univ, Ctr Hlth Decis Sci, Sch Publ Hlth, 718 Huntington Ave,2nd Fl, Boston, MA 02115 USA. EM dsoetema@hsph.harvard.edu FU Agency for Healthcare Research and Quality (AHRQ) [HHSA290200500161] FX This work was supported by contract HHSA290200500161 from the Agency for Healthcare Research and Quality (AHRQ). The views expressed in this article are those of the authors, and no official endorsement by AHRQ or the US Department of Health and Human Services is intended or should be inferred. NR 32 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUN PY 2013 VL 105 IS 11 BP 774 EP 781 DI 10.1093/jnci/djt096 PG 8 WC Oncology SC Oncology GA 160QK UT WOS:000320134100008 PM 23644480 ER PT J AU Ganz, PA Kwan, L Castellon, SA Oppenheim, A Bower, JE Silverman, DHS Cole, SW Irwin, MR Ancoli-Israel, S Belin, TR AF Ganz, Patricia A. Kwan, Lorna Castellon, Steven A. Oppenheim, Amy Bower, Julienne E. Silverman, Daniel H. S. Cole, Steve W. Irwin, Michael R. Ancoli-Israel, Sonia Belin, Thomas R. TI Cognitive Complaints After Breast Cancer Treatments: Examining the Relationship With Neuropsychological Test Performance SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STANDARD-DOSE CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; WORKING-MEMORY; SYSTEMIC CHEMOTHERAPY; VERBAL MEMORY; SURVIVORS; WOMEN; DYSFUNCTION; SYMPTOMS; THERAPY AB Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established. Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance. One hundred eighty-nine breast cancer patients, aged 2165 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (> 1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments (P .01), poorer NP verbal memory performance (P .02), and higher depressive symptoms (P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance (P .03) and higher depressive symptoms (P < .001), whereas combined chemotherapy and radiation treatment (P .05) approached statistical significance. About one in five postadjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research. C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Belin, Thomas R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Ganz, Patricia A.; Kwan, Lorna; Oppenheim, Amy] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. [Ganz, Patricia A.; Cole, Steve W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Silverman, Daniel H. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Bower, Julienne E.; Irwin, Michael R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Castellon, Steven A.; Bower, Julienne E.; Irwin, Michael R.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Bower, Julienne E.; Cole, Steve W.; Irwin, Michael R.] Univ Calif Los Angeles, Semel Inst, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. [Castellon, Steven A.] VA Greater Los Angeles Hlth Care Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, A2-125 CHS,Box 956900, Los Angeles, CA 90095 USA. EM pganz@mednet.ucla.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU National Cancer Institute [R01 CA 109650, R01-AG034588, R01-AG026364, R01-CA119159, R01-HL079955, R01 HL095799, P30-AG028748, UL RR 033176, R01CA112035]; Breast Cancer Research Foundation; National Institutes of Health; Cousins Center for Psychoneuroimmunology FX This research was supported by funding from the National Cancer Institute R01 CA 109650 and the Breast Cancer Research Foundation (to PAG); the National Institutes of Health and National Cancer Institute R01-AG034588; R01-AG026364; R01-CA119159; R01-HL079955; R01 HL095799; P30-AG028748; UL RR 033176 (to MRI), and the Cousins Center for Psychoneuroimmunology (to MRI); the National Cancer Institute R01CA112035 (to SA-I). NR 51 TC 43 Z9 44 U1 1 U2 31 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUN PY 2013 VL 105 IS 11 BP 791 EP 801 DI 10.1093/jnci/djt073 PG 11 WC Oncology SC Oncology GA 160QK UT WOS:000320134100010 PM 23606729 ER PT J AU Choi, HR Kwon, YM Freiberg, AA Nelson, SB Malchau, H AF Choi, Ho-Rim Kwon, Young-Min Freiberg, Andrew A. Nelson, Sandra B. Malchau, Henrik TI Periprosthetic Joint Infection with Negative Culture Results: Clinical Characteristics and Treatment Outcome SO JOURNAL OF ARTHROPLASTY LA English DT Article DE periprosthetic joint infection; negative culture result; clinical characteristics; treatment outcomes ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; EXCHANGE ARTHROPLASTY; DIAGNOSIS; FLUID; COUNT AB Negative culture result is frequently encountered in periprosthetic joint infection, but its clinical feature has not been well studied. In this study, clinical characteristics and treatment outcome were compared in two patient groups: (1) 40 periprosthetic joint infections with negative culture results (culture-negative group) and (2) 135 patients with positive culture results (culture-positive group). In comparison of two groups, the culture-negative group showed significantly higher incidence of prior antibiotic use (p = 0.005), higher incidence of prior resection surgery (p<0.001) and lower ESR (p = 0.02) than the culture-positive group. The success rate of infection control was higher in the culture-negative group (p = 0.006), which suggests that culture negativity may not necessarily be a negative prognostic factor for periprosthetic joint infection. (C) 2013 Published by Elsevier Inc. C1 [Choi, Ho-Rim; Kwon, Young-Min; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, Boston, MA 02114 USA. [Freiberg, Andrew A.] Massachusetts Gen Hosp, Dept Orthoped Surg, Adult Reconstruct Serv, Boston, MA 02114 USA. [Nelson, Sandra B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. OI Malchau, Henrik/0000-0002-4291-2441 NR 22 TC 14 Z9 16 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 2013 VL 28 IS 6 BP 899 EP 903 DI 10.1016/j.arth.2012.10.022 PG 5 WC Orthopedics SC Orthopedics GA 156TI UT WOS:000319846400005 PM 23523496 ER PT J AU Hess, PL Grau-Sepulveda, MV Hernandez, AF Peterson, ED Bhatt, DL Schwamm, LH Yancy, CW Fonarow, GC Al-Khatib, SM AF Hess, Paul L. Grau-Sepulveda, Maria V. Hernandez, Adrian F. Peterson, Eric D. Bhatt, Deepak L. Schwamm, Lee H. Yancy, Clyde W. Fonarow, Gregg C. Al-Khatib, Sana M. CA Get Guidelines Steering Comm & Hos TI Age Differences in the Use of Implantable Cardioverter-Defibrillators Among Older Patients Hospitalized with Heart Failure SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE age; implantable; defibrillator; heart failure; healthcare disparities; sex ID SUDDEN CARDIAC DEATH; PRACTICE SETTING FINDINGS; PRIMARY PREVENTION; MYOCARDIAL-INFARCTION; IMPROVE HF; OF-LIFE; OUTCOMES; CARE; SEX; DISPARITIES AB Age and ICD Use Among Older HF Patients Introduction Practice guidelines recommend the use of ICDs in patients with heart failure (HF) and a left ventricular ejection fraction (LVEF) of 35% in the absence of contraindications. Methods and Results We performed an analysis of ICD use among patients admitted with HF with LVEF of 35% and discharged alive from 251 hospitals participating in the American Heart Association's Get With The Guidelines-HF Program between January 2005 and September 2011. Among 35,772 guideline-eligible patients, 17,639 received an ICD prior to hospitalization (10,886), during hospitalization (4,876), or were discharged with plans to undergo ICD placement after hospitalization (1,877). After adjustment, increasing age was associated with lower ICD use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.87-0.91 per 5-year increase in age, P < 0.0001). Compared with patient age < 55 years, older age groups 65 years were less likely to receive an ICD (P < 0.003). Compared with men in the same age group, women were significantly less likely to receive an ICD; this difference was more marked with increasing age (P value for interaction = 0.006). There was a temporal increase in ICD use (adjusted OR 1.23, 95% CI 1.15-1.31 of ICD use per year) that was similar in each age group (P value for interaction = 0.665). Conclusions Eligible older HF patients age 65 years were significantly less likely to receive an ICD. With increasing age, women were less likely to receive an ICD than men. ICD use significantly increased over time in all age groups; however, age-related differences in ICD use persisted. C1 [Hess, Paul L.; Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.; Al-Khatib, Sana M.] Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC 27715 USA. [Hess, Paul L.; Hernandez, Adrian F.; Peterson, Eric D.; Al-Khatib, Sana M.] Duke Univ, Dept Med, Sch Med, Durham, NC 27715 USA. [Bhatt, Deepak L.] Vet Affairs Boston Hlth Syst, Boston, MA USA. [Bhatt, Deepak L.; Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Yancy, Clyde W.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. RP Hess, PL (reprint author), Duke Univ, Duke Clin Res Inst, Sch Med, POB 17969, Durham, NC 27715 USA. EM p.hess@duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association; Medtronic; Ortho-McNeil; American Heart Association Pharmaceuticals Roundtable; GlaxoSmithKline; GWTG Young Investigator Database Research Seed Grant; NIH [HL069749-09] FX Funding for the GWTG-HF program is provided by the American Heart Association. The GWTG-HF program is supported in part by Medtronic, Ortho-McNeil, and the American Heart Association Pharmaceuticals Roundtable. GWTG-HF was funded in the past by GlaxoSmithKline. This analysis was funded by the GWTG Young Investigator Database Research Seed Grant. The sponsors of GWTG-HF had no role in the design or conduct of the study or the management, analysis, or interpretation of the data. P.L. Hess was funded by NIH T-32 training grant HL069749-09. NR 31 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUN PY 2013 VL 24 IS 6 BP 664 EP 671 DI 10.1111/jce.12100 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 157LV UT WOS:000319898500010 PM 23437793 ER PT J AU Lee, J Radhakrishnan, H Wu, WC Daneshmand, A Climov, M Ayata, C Boas, DA AF Lee, Jonghwan Radhakrishnan, Harsha Wu, Weicheng Daneshmand, Ali Climov, Mihail Ayata, Cenk Boas, David A. TI Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acute stroke; animal models; cerebral blood flow measurement; microscopy; optical imaging ID FLUORESCENCE CORRELATION SPECTROSCOPY; ISCHEMIC-STROKE; IN-VIVO; NONERGODIC MEDIA; DIFFUSION; RAT; MICROSCOPY; PERFUSION; CORTEX; MRI AB This paper describes a novel optical method for label-free quantitative imaging of cerebral blood flow (CBF) and intracellular motility (IM) in the rodent cerebral cortex. This method is based on a technique that integrates dynamic light scattering (DLS) and optical coherence tomography (OCT), named DLS-OCT. The technique measures both the axial and transverse velocities of CBF, whereas conventional Doppler OCT measures only the axial one. In addition, the technique produces a three-dimensional map of the diffusion coefficient quantifying nontranslational motions. In the DLS-OCT diffusion map, we observed high-diffusion spots, whose locations highly correspond to neuronal cell bodies and whose diffusion coefficient agreed with that of the motion of intracellular organelles reported in vitro in the literature. Therefore, the present method has enabled, for the first time to our knowledge, label-free imaging of the diffusion-like motion of intracellular organelles in vivo. As an example application, we used the method to monitor CBF and IM during a brief ischemic stroke, where we observed an induced persistent reduction in IM despite the recovery of CBF after stroke. This result supports that the IM measured in this study represent the cellular energy metabolism-related active motion of intracellular organelles rather than free diffusion of intracellular macromolecules. C1 [Lee, Jonghwan; Wu, Weicheng; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Radhakrishnan, Harsha] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA. [Daneshmand, Ali; Climov, Mihail; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA. RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, 149 13th St,Room 2280, Charlestown, MA 02129 USA. EM jonghwan@nmr.mgh.harvard.edu OI Climov, Mihail/0000-0001-9150-8608 FU NIH [R01-NS057476, R01-EB000790, P01NS055104]; AFOSR [MFEL FA9550-07-1-0101] FX This study was supported by the NIH (R01-NS057476, R01-EB000790, P01NS055104) and the AFOSR (MFEL FA9550-07-1-0101). NR 43 TC 19 Z9 19 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2013 VL 33 IS 6 BP 819 EP 825 DI 10.1038/jcbfm.2013.20 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 156KP UT WOS:000319821100004 PM 23403378 ER PT J AU Abrahamson, EE Foley, LM DeKosky, ST Hitchens, TK Ho, C Kochanek, PM Ikonomovic, MD AF Abrahamson, Eric E. Foley, Lesley M. DeKosky, Steven T. Hitchens, T. Kevin Ho, Chien Kochanek, Patrick M. Ikonomovic, Milos D. TI Cerebral blood flow changes after brain injury in human amyloid-beta knock-in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Alzheimer's disease; amyloid; arterial spin-labeling MRI; blood flow; brain injury; statin ID TRAUMA-INDUCED INCREASES; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; A-BETA; FUNCTIONAL HYPEREMIA; REDUCTASE INHIBITORS; OXIDATIVE STRESS; SIMVASTATIN; ACTIVATION AB Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer's disease (AD). Increased brain concentrations of amyloid-beta (A beta) peptides and impaired cerebral blood flow (CBF) are shared pathologic features of TBI and AD and promising therapeutic targets. We used arterial spin-labeling magnetic resonance imaging to examine if CBF changes after TBI are influenced by human A beta and amenable to simvastatin therapy. CBF was measured 3 days and 3 weeks after controlled cortical impact (CCI) injury in transgenic human A beta-expressing APP(NLh/NLh) mice compared to murine A beta-expressing C57Bl/6J wild types. Compared to uninjured littermates, CBF was reduced in the cortex of the injured hemisphere in both A beta transgenics and wild types; deficits were more pronounced in the transgenic group, which exhibited injury-induced increased concentrations of human A beta. In the hemisphere contralateral to CCI, CBF levels were stable in A beta transgenic mice but increased in wild-type mice, both relative to uninjured littermates. Post-injury treatment of A beta transgenic mice with simvastatin lowered brain A beta concentrations, attenuated deficits in CBF ipsilateral to injury, restored hyperemia contralateral to injury, and reduced brain tissue loss. Future studies examining long-term effects of simvastatin therapy on CBF and chronic neurodegenerative changes after TBI are warranted. C1 [Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Foley, Lesley M.; Hitchens, T. Kevin; Ho, Chien] Carnegie Mellon Univ, Dept Biol Sci, VA Pittsburgh Healthcare Syst, Pittsburgh NMR Ctr Biomed Res, Pittsburgh, PA 15213 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Kochanek, Patrick M.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Kochanek, Patrick M.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, BSTWR S-521,200 Lothrop St, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu RI Kochanek, Patrick/D-2371-2015; Ho, Chien/O-6112-2016 OI Kochanek, Patrick/0000-0002-2627-913X; Ho, Chien/0000-0002-4094-9232 FU NIH [P50 NS30318]; National Institutes of Health [P41-EB001977] FX Supported by NIH P50 NS30318. The Pittsburgh NMR Center for Biomedical Research is supported by a grant from the National Institutes of Health (P41-EB001977). We acknowledge expert technical assistance provided by Mr. William Paljug, Mr. John Melick, and Ms. Lan Shao. NR 37 TC 5 Z9 5 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2013 VL 33 IS 6 BP 826 EP 833 DI 10.1038/jcbfm.2013.24 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 156KP UT WOS:000319821100005 PM 23443172 ER PT J AU Huang, S Kim, JK Atochin, DN Farrar, CT Huang, PL Suh, JY Kwon, SJ Shim, WH Cho, H Cho, G Kim, YR AF Huang, Shuning Kim, Jeong Kon Atochin, Dmitriy N. Farrar, Christian T. Huang, Paul L. Suh, Ji Yeon Kwon, Seon Joo Shim, Woo Hyun Cho, Hyungjoon Cho, Gyunggoo Kim, Young Ro TI Cerebral blood volume affects blood-brain barrier integrity in an acute transient stroke model SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; cerebral blood volume; stroke; water exchange; MRI ID ACUTE ISCHEMIC-STROKE; WATER EXCHANGE; HEMORRHAGIC TRANSFORMATION; MAGNETIC-RESONANCE; MATRIX METALLOPROTEINASES; EDEMA FORMATION; PERFUSION CT; RAT-BRAIN; GD-DTPA; MRI AB Insufficient vascular reserve after an ischemic stroke may induce biochemical cascades that subsequently deteriorate the blood-brain barrier (BBB) function. However, the direct relationship between poor cerebral blood volume (CBV) restoration and BBB disruption has not been examined in acute stroke. To quantify BBB integrity at acute stages of transient stroke, in particular for cases in which extravasation of the standard contrast agent (Gd-DTPA) is not observed, we adopted the water exchange index (WEI), a novel magnetic resonance image-derived parameter to estimate the water permeability across the BBB. The apparent diffusion coefficient (ADC) and R-2 relaxation rate constant were also measured for outlining the tissue abnormality, while fractional CBV and WEI were quantified for assessing vascular alterations. The significantly decreased ADC and R-2 in the ischemic cortices did not correlate with the changes in CBV or WEI. In contrast, a strong negative correlation between the ipsilesional WEI and CBV was found, in which stroke mice were clustered into two groups: (1) high WEI and low CBV and (2) normal WEI and CBV. The low CBV observed for mice with a disrupted BBB, characterized by a high WEI, indicates the importance of CBV restoration for maintaining BBB stability in acute stroke. C1 [Huang, Shuning; Kim, Jeong Kon; Farrar, Christian T.; Suh, Ji Yeon; Kwon, Seon Joo; Shim, Woo Hyun; Kim, Young Ro] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Kim, Jeong Kon; Cho, Gyunggoo] Korea Basic Sci Inst, Div Magnet Resonance, Ochang, South Korea. [Kim, Jeong Kon; Suh, Ji Yeon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Charlestown, MA 02129 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. [Cho, Hyungjoon; Kim, Young Ro] Ulsan Natl Inst Sci & Technol, Ulsan, South Korea. RP Kim, YR (reprint author), Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Bldg 149,13th St, Charlestown, MA 02129 USA. EM spmn@nmr.mgh.harvard.edu RI Cho, HyungJoon/F-1423-2010; Atochin, Dmitriy/Q-3150-2016 FU American Heart Association (SDG) [0835451N]; Basic Science Research Program [2011-0028826]; Advanced Research Center through the National Research Foundation of Korea (NRF) [2012-0008999]; Ministry of Education, Science of Technology; National Institutes of Health [K25-AG029415] FX The authors gratefully acknowledge financial support from the American Heart Association (SDG #0835451N), the Basic Science Research Program (No. 2011-0028826), and Advanced Research Center (No. 2012-0008999) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science of Technology and the National Institutes of Health (K25-AG029415). NR 39 TC 5 Z9 7 U1 5 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2013 VL 33 IS 6 BP 898 EP 905 DI 10.1038/jcbfm.2013.27 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 156KP UT WOS:000319821100013 PM 23462571 ER PT J AU Ayata, C Shin, HK Dilekoz, E Atochin, DN Kashiwagi, S Eikermann-Haerter, K Huang, PL AF Ayata, Cenk Shin, Hwa Kyoung Dilekoez, Ergin Atochin, Dmitriy N. Kashiwagi, Satoshi Eikermann-Haerter, Katharina Huang, Paul L. TI Hyperlipidemia disrupts cerebrovascular reflexes and worsens ischemic perfusion defect SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apolipoprotein E knockout mice; autoregulation; hypercapnia; hypercholesterolemia; middle cerebral artery occlusion; neurovascular coupling ID APOLIPOPROTEIN-E-DEFICIENT; CEREBRAL-BLOOD-FLOW; FAMILIAL HYPERCHOLESTEROLEMIA; DENSITY-LIPOPROTEIN; CO2 REACTIVITY; MICE; ATHEROSCLEROSIS; DYSFUNCTION; STROKE; BRAIN AB Hyperlipidemia is a highly prevalent risk factor for coronary and cervical atherosclerosis and stroke. However, even in the absence of overt atherosclerosis, hyperlipidemia disrupts endothelial and smooth muscle function. We investigated the impact of hyperlipidemia on resting-brain perfusion, fundamental cerebrovascular reflexes, and dynamic perfusion defect during acute focal ischemia in hyperlipidemic apolipoprotein E knockout mice before the development of flow-limiting atherosclerotic stenoses. Despite elevated blood pressures, absolute resting cerebral blood flow was reduced by 20% in apolipoprotein E knockout compared with wild type when measured by [C-14]-iodoamphetamine technique. Noninvasive, high spatiotemporal resolution laser speckle flow imaging revealed that the lower autoregulatory limit was elevated in apolipoprotein E knockout mice (60 vs. 40 mm Hg), and cortical hyperemic responses to hypercapnia and functional activation were attenuated by 30% and 64%, respectively. Distal middle cerebral artery occlusion caused significantly larger perfusion defects and infarct volumes in apolipoprotein E knockout compared with wild type. Cerebrovascular dysfunction showed a direct relationship to the duration of high-fat diet. These data suggest that hyperlipidemia disrupts cerebral blood flow regulation and diminishes collateral perfusion in acute stroke in the absence of hemodynamically significant atherosclerosis. C1 [Ayata, Cenk; Shin, Hwa Kyoung; Dilekoez, Ergin; Eikermann-Haerter, Katharina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv & Neurosci Intens Care Un, Charlestown, MA 02129 USA. [Atochin, Dmitriy N.; Kashiwagi, Satoshi; Huang, Paul L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Atochin, Dmitriy N.; Kashiwagi, Satoshi; Huang, Paul L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Atochin, Dmitriy/Q-3150-2016 FU National Institutes of Health [NS055104, NS061505, NS33335]; American Heart Association [SDG0835344N]; National Research Foundation (NRF) of Korea; Ministry of Education, Science and Technology, Harvard Catalyst [2010-0007470]; Harvard Clinical and Translational Science Center (NIH) [UL1RR025758]; Harvard University and its affiliated academic health care centers; Deane Institute for Integrative Research in Stroke and Atrial Fibrillation; Andrew David Heitman Foundation FX This work was supported by the National Institutes of Health (NS055104, NS061505, NS33335), American Heart Association (SDG0835344N), Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (Grants 2010-0007470), Harvard Catalyst. The Harvard Clinical and Translational Science Center (NIH Award #UL1RR025758 and financial contributions from Harvard University and its affiliated academic health care centers), the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation, and Neuroendovascular Research Fund from the Andrew David Heitman Foundation. NR 38 TC 11 Z9 13 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2013 VL 33 IS 6 BP 954 EP 962 DI 10.1038/jcbfm.2013.38 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 156KP UT WOS:000319821100020 PM 23486293 ER PT J AU Basile, JN Bloch, MJ AF Basile, Jan N. Bloch, Michael J. TI Determining the Relative Antihypertensive Potency and Relative Cardiovascular Risk Reduction Associated With Different Thiazide and Thiazide-Type Diuretics SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. RP Bloch, MJ (reprint author), Univ Hlth Syst, 1500 East 2nd St,Suite 302, Reno, NV 89502 USA. EM mbloch@aol.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2013 VL 15 IS 6 BP 359 EP 361 DI 10.1111/jch.12079 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 157MA UT WOS:000319899000001 PM 23730981 ER PT J AU Sharma, DB Bondell, HD Zhang, HH AF Sharma, Dhruv B. Bondell, Howard D. Zhang, Hao Helen TI Consistent Group Identification and Variable Selection in Regression With Correlated Predictors SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE Coefficient shrinkage; Correlation; Oracle properties; Penalization; Structure identification; Supervised clustering ID ORACLE PROPERTIES; ADAPTIVE LASSO; ELASTIC-NET; SHRINKAGE; MODEL AB Statistical procedures for variable selection have become integral elements in any analysis. Successful procedures are characterized by high predictive accuracy, yielding interpretable models while retaining computational efficiency. Penalized methods that perform coefficient shrinkage have been shown to be successful in many cases. Models with correlated predictors are particularly challenging to tackle. We propose a penalization procedure that performs variable selection while clustering groups of predictors automatically. The oracle properties of this procedure, including consistency in group identification, are also studied. The proposed method compares favorably with existing selection approaches in both prediction accuracy and model discovery, while retaining its computational efficiency. Supplementary materials are available online. C1 [Sharma, Dhruv B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sharma, Dhruv B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bondell, Howard D.; Zhang, Hao Helen] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. RP Sharma, DB (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM dbsharma@hsph.harvard.edu; howard_bondell@ncsu.edu; helen_zhang@ncsu.edu FU NIH (National Institutes of Health) [P01-CA-134294, R01-MH-084022, P01-CA-142538, R01-CA-085848, P01-CA-142538.]; NSF (National Science Foundation) [DMS-1005612, DMS-0645293] FX The authors are grateful to the editor, an associate editor, and two anonymous referees for their valuable comments. Sharma's research was supported in part by the NIH (National Institutes of Health) grant P01-CA-134294. Bondell's research was supported in part by the NSF (National Science Foundation) grant DMS-1005612 and NIH grants R01-MH-084022 and P01-CA-142538. Zhang's research was supported in part by the NSF grant DMS-0645293 and NIH grants R01-CA-085848 and P01-CA-142538. NR 22 TC 8 Z9 9 U1 0 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1061-8600 EI 1537-2715 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD JUN PY 2013 VL 22 IS 2 BP 319 EP 340 DI 10.1080/15533174.2012.707849 PG 22 WC Statistics & Probability SC Mathematics GA 158FD UT WOS:000319954000006 PM 23772171 ER PT J AU Reinherz, EL Kung, PC Goldstein, G Schlossman, SF AF Reinherz, Ellis L. Kung, Patrick C. Goldstein, Gideon Schlossman, Stuart F. TI Separation of functional subsets of human T cells by a monoclonal antibody (Reprinted from Proceedings of the National Academy of Sciences, U.S.A., vol 76, pg 4061-4065, 1979) SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID HUMAN LYMPHOCYTE SUBPOPULATIONS; IMMUNOLOGICAL FUNCTIONS; SUPPRESSOR; SUBCLASSES; DISEASE; BLOOD; TH2+ AB A monoclonal antibody was produced to human peripheral blood T cells. This hybridoma antibody, termed OKT4, was reactive by indirect immunofluorescence with only 55-60% of the peripheral blood T cell population (OKT4(+)) and unreactive with normal B cells, null cells, and macrophages. The OKT4(-) T cell population contained the previously described TH2+ subset that has been shown to contain cytotoxie/suppressor cells. With cell-sorter separation of OKT4(+) and OKT4(-) cells, it was shown that these T cell subsets were functionally discrete. Both gave proliferative responses with concanavalin A, alloantigens, and phytohemagglutinin, although OKT4(+) cells were much more responsive to the latter. OKT4(+) cells alone responded to soluble antigens whereas OKT4(-) cells alone were cytotoxic after alloantigenic sensitization of unfractionated T cells. However, both OKT4(+) and OKT4(-) cells were required during sensitization for optimal development of cytotoxicity. These data suggest that the OKT4(+) subset represents a helper population and that the OKTA4(-) subset contains the cytotoxic effector population. OKT4 could be a valuable reagent for determining alterations of these functional subsets in human diseases. C1 [Reinherz, Ellis L.; Schlossman, Stuart F.] Harvard Univ, Sch Med, Sidney Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. [Kung, Patrick C.; Goldstein, Gideon] Ortho Pharmaceut Corp, Div Immunosci, Raritan, NJ 08869 USA. RP Reinherz, EL (reprint author), Sidney Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 0 Z9 0 U1 2 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2013 VL 190 IS 11 BP 5346 EP 5350 PG 5 WC Immunology SC Immunology GA 147XY UT WOS:000319205900004 PM 23687191 ER PT J AU Kung, PC Goldstein, G Reinherz, EL Schlossman, SF AF Kung, Patrick C. Goldstein, Gideon Reinherz, Ellis L. Schlossman, Stuart F. TI Monoclonal Antibodies Defining Distinctive Human T Cell Surface Antigens (Reprinted from Science, vol 206, pg 347, 1979) SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID GLOBULIN; SUBSET AB Three novel monoclonal antibodies. (designated OKT1, OKT3 and OKT4) were generated against surface determinants of human peripheral T cells. Both OKT1 and OKT3 reacted with till human peripheral T cells and 5 to 10 percent of thymocytes but differed in their reactivities with T cell lines. By contrast, OKT4 reacted with 55 percent of human peripheral T cells and 80 percent of thymocytes, three antibodies were selective for T cells in the peripheral blood in that they did not react with normal B cells, null cells, monocytes. or granulocytes. C1 [Kung, Patrick C.; Goldstein, Gideon] Ortho Pharmaceut Corp, Raritan, NJ 08869 USA. [Reinherz, Ellis L.; Schlossman, Stuart F.] Harvard Univ, Sch Med, Sidney Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Kung, PC (reprint author), Ortho Pharmaceut Corp, Raritan, NJ 08869 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2013 VL 190 IS 11 BP 5351 EP 5353 PG 3 WC Immunology SC Immunology GA 147XY UT WOS:000319205900005 PM 23687192 ER PT J AU Giallourakis, CC Benita, Y Molinie, B Cao, ZF Despo, O Pratt, HE Zukerberg, LR Daly, MJ Rioux, JD Xavier, RJ AF Giallourakis, Cosmas C. Benita, Yair Molinie, Benoit Cao, Zhifang Despo, Orion Pratt, Henry E. Zukerberg, Lawrence R. Daly, Mark J. Rioux, John D. Xavier, Ramnik J. TI Genome-wide Analysis of Immune System Genes by Expressed Sequence Tag Profiling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONCODING RNAS; FRUCTOSE 1,6-BISPHOSPHATASE; IMMUNOLOGICAL GENOME; DATABASE; CELLS; IDENTIFICATION; TRANSCRIPTOME; INFORMATION; ANNOTATION; MECHANISMS AB Profiling studies of mRNA and microRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some instances, functional studies have been subsequently pursued. Recent efforts such as the Encyclopedia of DNA Elements have demonstrated the benefit of coupling RNA sequencing analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including noncoding RNAs. As a result, we have established the Immunogene database, representing an integrated EST road map of gene expression in human immune cells, which can be used to further investigate the function of coding and noncoding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus, we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes. C1 [Giallourakis, Cosmas C.; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Giallourakis, Cosmas C.; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Zukerberg, Lawrence R.; Daly, Mark J.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Giallourakis, Cosmas C.; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Benita, Yair; Cao, Zhifang; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Daly, Mark J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA. [Daly, Mark J.; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA. [Rioux, John D.] Univ Montreal, Lab Genet & Genom Med Inflammat, Montreal, PQ H1T 1C8, Canada. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu RI Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU National Institutes of Health [DK083756, DK086502, HL088297, DK043351] FX This work was supported by Grants DK083756, DK086502, HL088297, and DK043351 from the National Institutes of Health (to R.J.X.). NR 37 TC 5 Z9 5 U1 1 U2 19 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2013 VL 190 IS 11 BP 5578 EP 5587 DI 10.4049/jimmunol.1203471 PG 10 WC Immunology SC Immunology GA 147XY UT WOS:000319205900028 PM 23616578 ER PT J AU Eisenberg, G Uzana, R Pato, A Frankenburg, S Merims, S Yefenof, E Ferrone, S Peretz, T Machenkin, A Lotem, M AF Eisenberg, Galit Uzana, Ronny Pato, Aviad Frankenburg, Shoshana Merims, Sharon Yefenof, Eitan Ferrone, Soldano Peretz, Tamar Machenkin, Arthur Lotem, Michal TI Imprinting of Lymphocytes with Melanoma Antigens Acquired by Trogocytosis Facilitates Identification of Tumor-Reactive T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADOPTIVE TRANSFER THERAPY; FLOW-CYTOMETRY; INFILTRATING LYMPHOCYTES; MEMBRANE-FRAGMENTS; TARGET-CELLS; NK CELLS; B-CELL; CAPTURE; ACTIVATION; GENERATION AB Trogocytosis is a contact-dependent intercellular transfer of membrane fragments and associated molecules from APCs to effector lymphocytes. We previously demonstrated that trogocytosis also occurs between tumor target and cognate melanoma Ag-specific cytotoxic T cells (CTL). In this study, we show that, following trogocytosis, immune effector cells acquire molecular components of the tumor, including surface Ags, which are detectable by specific mAbs. We demonstrate that CD8(+) and CD4(+) T cells from melanoma patients' PBMC and tumor-infiltrating lymphocytes (TIL) capture melanoma Ags, enabling identification of trogocytosing lymphocytes by staining with Ag-specific Abs. This finding circumvents the necessity of tumor prelabeling, which in the past was mandatory to detect membrane-capturing T cells. Through the detection of melanoma Ags on TIL, we sorted trogocytosing T cells and verified their preferential reactivity and cytotoxicity. Furthermore, tumor Ag imprinted T cells were detected at low frequency in fresh TIL cultures shortly after extraction from the tumor. Thus, T cell imprinting by tumor Ags may allow the enrichment of melanoma Ag-specific T cells for research and potentially even for the adoptive immunotherapy of patients with cancer. The Journal of Immunology, 2013, 190: 5856-5865. C1 [Eisenberg, Galit; Uzana, Ronny; Pato, Aviad; Frankenburg, Shoshana; Merims, Sharon; Peretz, Tamar; Machenkin, Arthur; Lotem, Michal] Hadassah Med Org, Sharett Inst Oncol, IL-91120 Jerusalem, Israel. [Yefenof, Eitan] Hebrew Univ Jerusalem, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. [Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Machenkin, A (reprint author), Hadassah Med Org, Sharett Inst Oncol, POB 12000, IL-91120 Jerusalem, Israel. EM arthurm@hadassah.org.il; mlotem@hadassah.org.il FU Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; United States-Israel Binational Science Foundation; Israel Cancer Association FX This work was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the United States-Israel Binational Science Foundation, the Israel Cancer Association, the Chief Scientist of the Israel Ministry of Health (Grant 4886), and a Perlstein Family donation. This work was also supported by Public Health Service Grants RO1 CA110249 and RO1 CA138188 awarded by the National Cancer Institute. NR 38 TC 7 Z9 7 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2013 VL 190 IS 11 BP 5856 EP 5865 DI 10.4049/jimmunol.1202879 PG 10 WC Immunology SC Immunology GA 147XY UT WOS:000319205900057 PM 23626012 ER PT J AU Cai, CS Twyford, P Fried, S AF Cai, Changsi Twyford, Perry Fried, Shelley TI The response of retinal neurons to high-frequency stimulation SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID ACTION-POTENTIAL INITIATION; ISOLATED CHICKEN RETINA; GANGLION-CELLS; ELECTRICAL-STIMULATION; VISUAL-PERCEPTION; CONDUCTION BLOCK; NATURAL SCENES; PULSE TRAINS; MAMMALIAN RETINA; IN-VITRO AB Objective. High-rate pulse trains have proven to be effective in cochlear prosthetics and, more recently, have been shown to elicit a wide range of interesting response properties in axons of the peripheral nervous system. Surprisingly, the effectiveness of such trains for use in retinal prostheses has not been explored. Approach. Using cell-attached patch clamp methods, we measured the in vitro response of two rabbit retinal ganglion cell types, OFF-brisk transient (OFF-BT) and ON-OFF directionally selective (DS), to trains of biphasic pulses delivered at 2000 pulses per second (PPS). Main Results. For OFF-BT cells, response onset occurred at similar to 20 mu A, and maximum response occurred at similar to 40 mu A. Interestingly, spiking levels decreased for further increases in amplitude. In contrast, DS cells had a spiking onset at similar to 25 mu A and maintained strong spiking as stimulus amplitude was increased, even at the highest levels tested. Thus, a low-amplitude stimulus train at 2000 PPS (similar to 25 mu A) will activate OFF-BT cells strongly, while simultaneously activating DS cells only weakly. In contrast, a high amplitude train (similar to 75 mu A) will activate DS cells strongly while suppressing responses in OFF-BT cells. Significance. The response differences between cell types suggest some forms of preferential activation may be possible, and further testing is warranted. Further, the scope of the response differences found here suggests activation mechanisms that are more complex than those described in previous studies. C1 [Cai, Changsi; Twyford, Perry; Fried, Shelley] VA Boston Healthcare Syst, Boston, MA USA. [Cai, Changsi] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China. [Cai, Changsi; Twyford, Perry; Fried, Shelley] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Cai, Changsi; Twyford, Perry; Fried, Shelley] Harvard Univ, Sch Med, Boston, MA USA. [Cai, Changsi] Aarhus Univ, CFIN, Aarhus, Denmark. RP Fried, S (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM fried.shelley@mgh.harvard.edu FU VA Boston Healthcare System [1 I01RX000350]; NIH [1 R01EY019967-01] FX This work was funded in part by the VA Boston Healthcare System (1 I01RX000350) and the NIH (1 R01EY019967-01). NR 62 TC 9 Z9 9 U1 2 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2013 VL 10 IS 3 AR UNSP 036009 DI 10.1088/1741-2560/10/3/036009 PG 14 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 152DM UT WOS:000319510800012 PM 23594620 ER PT J AU Perge, JA Homer, ML Malik, WQ Cash, S Eskandar, E Friehs, G Donoghue, JP Hochberg, LR AF Perge, Janos A. Homer, Mark L. Malik, Wasim Q. Cash, Sydney Eskandar, Emad Friehs, Gerhard Donoghue, John P. Hochberg, Leigh R. TI Intra-day signal instabilities affect decoding performance in an intracortical neural interface system SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID HIPPOCAMPAL PYRAMIDAL CELLS; BRAIN-MACHINE INTERFACE; LOCAL-FIELD POTENTIALS; FALSE DISCOVERY RATE; PRIMARY MOTOR CORTEX; CORTICAL CONTROL; SPIKING ACTIVITY; MUSCLE-ACTIVITY; TETRAPLEGIA; ENSEMBLE AB Objective. Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach. To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results. 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 +/- 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 +/- 6.5 mu V or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional 'bias' in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions. Significance. We anticipate that signal acquisition and decoding methods that can adapt to the reported instabilities will further improve the performance of intracortically-based NISs. C1 [Perge, Janos A.; Malik, Wasim Q.; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Perge, Janos A.; Homer, Mark L.; Malik, Wasim Q.; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Perge, Janos A.; Malik, Wasim Q.; Donoghue, John P.; Hochberg, Leigh R.] Rehabil R&D Serv, Dept Vet Affairs Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Homer, Mark L.] Brown Univ, Providence, RI 02912 USA. [Malik, Wasim Q.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cash, Sydney; Eskandar, Emad; Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA USA. [Cash, Sydney; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Friehs, Gerhard] Rhode Isl Hosp, Dept Neurosurg, Providence, RI USA. [Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. RP Perge, JA (reprint author), Brown Univ, Sch Engn, Providence, RI 02912 USA. EM janos_perge@brown.edu OI Hochberg, Leigh/0000-0003-0261-2273 FU NIH: NIDCD [R01DC009899]; NIH: NICHD-NCMRR [N01HD53403, N01HD10018]; Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs [B6310N, B6453R, B6459L]; DARPA REPAIR [N66001-10-C-2010]; Department of Defense (CIMIT USAMRAA); Doris Duke Charitable Foundation; MGH-Deane Institute; Katie Samson Foundation; Cyberkinetics Neurotechnology Systems, Inc.; Massachusetts General Hospital; Spaulding Rehabilitation Hospital FX We are grateful to participants S3, A1, and T1 for their dedication to this research, to the caregiver staff at The Boston Home, to Cindy Chestek for valuable comments on the manuscript, and to John Simeral for contributing analysis software. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. This work was supported by NIH: NIDCD (R01DC009899) and NICHD-NCMRR (N01HD53403, N01HD10018); Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs (B6310N, B6453R, and B6459L); DARPA REPAIR (N66001-10-C-2010); Department of Defense (CIMIT USAMRAA); Doris Duke Charitable Foundation, MGH-Deane Institute, and Katie Samson Foundation. The pilot clinical trial from which these data are derived was sponsored in part by Cyberkinetics Neurotechnology Systems, Inc. JPD is a former Chief Scientific Officer and director of Cyberkinetics Neurotechnology Systems, Inc. (CKI); he held stocks and received compensation. LRH received research support from Massachusetts General and Spaulding Rehabilitation Hospitals, which in turn received clinical trial support from CKI. CKI ceased operations in 2009. The BrainGate pilot clinical trial is now directed by Massachusetts General Hospital. CAUTION: Investigational Device. Limited by Federal Law to Investigational Use. NR 67 TC 29 Z9 29 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2013 VL 10 IS 3 AR 036004 DI 10.1088/1741-2560/10/3/036004 PG 14 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 152DM UT WOS:000319510800007 PM 23574741 ER PT J AU Naab, F Brown, R Heidrich, S AF Naab, Florence Brown, Roger Heidrich, Susan TI Psychosocial Health of Infertile Ghanaian Women and Their Infertility Beliefs SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE Beliefs; infertility; psychosocial; women ID REPRESENTATIONAL APPROACH; PATIENT EDUCATION; TREATMENT-SEEKING; SOUTH-AFRICA; RESPONSES; PREVALENCE; VALIDATION; CHILDREN; STRESS; TRIAL AB Purpose The purpose of this study was to describe infertile women's psychosocial health problems and their infertility-related beliefs and examine the relationships between their beliefs about infertility and psychosocial health problems. Design The study was a descriptive correlational cross-sectional survey. Women (N = 203) who were receiving treatment for fertility problems in two public hospitals in Ghana were recruited. Methods Participants completed a Fertility Belief Questionnaire; measures of infertility-related stress, anxiety, social isolation, perceived stigma, and depressive symptoms; and sociodemographic and infertility-related health questions. Descriptive statistics, Pearson's correlations, and hierarchical regression analyses were performed. Findings The women reported high levels of infertility-related stress, low levels of anxiety, some social isolation, low levels of perceived stigma, and high levels of depressive symptoms. Beliefs that infertility has negative consequences and that one has a poor understanding of infertility were significantly related to infertility-related stress, social isolation, and depressive symptoms. Belief that infertility could be managed by personal control was significantly related to lower levels of anxiety and perceived stigma. Beliefs about consequences, illness coherence, and personal control explained significant proportions of the variances in anxiety, stress, social isolation, perceived stigma, and depressive symptoms. Conclusions Infertile women in Ghana have psychosocial health problems that are associated with their beliefs about infertility. Clinical Relevance Findings have implications for nursing care of infertile women in Ghana. C1 [Naab, Florence] Univ Ghana, Dept Maternal & Child Hlth, Sch Nursing, Coll Hlth Sci, Legon, Accra, Ghana. [Brown, Roger] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Brown, Roger] Univ Wisconsin, Sch Med, Madison, WI USA. [Brown, Roger] Univ Wisconsin, Sch Publ Hlth, Madison, WI USA. [Heidrich, Susan] Univ Wisconsin, Madison, WI USA. [Heidrich, Susan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Naab, F (reprint author), Univ Ghana, Dept Maternal & Child Hlth, Sch Nursing, Coll Hlth Sci, POB LG 43, Legon Boundary, Accra, Ghana. EM florencenaab@yahoo.com NR 41 TC 4 Z9 4 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD JUN PY 2013 VL 45 IS 2 BP 132 EP 140 DI 10.1111/jnu.12013 PG 9 WC Nursing SC Nursing GA 157OA UT WOS:000319906400005 PM 23731032 ER PT J AU Sherry, D Fennessy, MM Benavente, VG Ruppar, TM Collins, EG AF Sherry, Daisy Fennessy, Michelle M. Benavente, Viola G. Ruppar, Todd M. Collins, Eileen G. TI Important Considerations When Applying for a Postdoctoral Fellowship SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE Postdoctoral nurse fellowship; graduate training; nurse education ID OPPORTUNITIES; GRANTS; NINR AB Purpose To examine important decision points that graduates should consider before applying for a postdoctoral fellowship. Methods A literature review was performed. Findings and Conclusions A synthesis of the present data on the postdoctoral fellowship, eligibility criteria, application process, and important considerations was provided. Experiential knowledge from four present postdoctoral fellows was included. The goals, advantages, and disadvantages of the fellowship were discussed. In conclusion, the postdoctoral fellowship was examined to offer important considerations in the decision to pursue this opportunity. Clinical Relevance The clinical relevance of this article is related to the training and education of nurses to become the next generation of independent, successful scholars and scientists. Postdoctoral training adds valuable contributions and quality to the field of nursing. C1 [Sherry, Daisy] US Dept Vet Affairs, Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [Fennessy, Michelle M.] Univ Calif Davis Hlth Syst, Betty Irene Moore Sch Nursing, Sacramento, CA USA. [Benavente, Viola G.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Ruppar, Todd M.] Univ Missouri, Sinclair Sch Nursing, Columbia, MO USA. [Collins, Eileen G.] US Dept Vet Affairs, Dept Rehabil, Hines, IL 60141 USA. RP Sherry, D (reprint author), US Dept Vet Affairs, Edward Hines Jr VA Hosp, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM daisyc6@juno.com RI Ruppar, Todd/B-8091-2015 OI Ruppar, Todd/0000-0003-0794-5544 FU U.S. Department of Veterans Affairs; Gordon & Betty Moore Foundation; Ruth L. Kirschstein National Research Institutional Training Program; National Institutes of Health, National Institute of Nursing Research [T32NR007106]; John A. Hartford Foundation; Atlantic Philanthropies Claire M. Fagin Fellowship FX Dr. Sherry is funded by the U.S. Department of Veterans Affairs Postdoctoral Fellowship. Dr. Fennessy is funded by a fellowship through the Gordon & Betty Moore Foundation. Dr. Benavente is funded by a Ruth L. Kirschstein National Research Institutional Training Program funded by the National Institutes of Health, National Institute of Nursing Research, T32NR007106 Biobehavioral Nursing Research Training Program (principal investigator Dr. Carol Landis). Dr. Ruppar is funded by a John A. Hartford Foundation and Atlantic Philanthropies Claire M. Fagin Fellowship. NR 21 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD JUN PY 2013 VL 45 IS 2 BP 210 EP 218 DI 10.1111/jnu.12012 PG 9 WC Nursing SC Nursing GA 157OA UT WOS:000319906400014 PM 23452068 ER PT J AU Epstein, AS Volandes, AE Chen, LY Gary, KA Li, YL Agre, P Levin, TT Reidy, DL Meng, RD Segal, NH Yu, KH Abou-Alfa, GK Janjigian, YY Kelsen, DP O'Reilly, EM AF Epstein, Andrew S. Volandes, Angelo E. Chen, Ling Y. Gary, Kristen A. Li, Yuelin Agre, Patricia Levin, Tomer T. Reidy, Diane L. Meng, Raymond D. Segal, Neil H. Yu, Kenneth H. Abou-Alfa, Ghassan K. Janjigian, Yelena Y. Kelsen, David P. O'Reilly, Eileen M. TI A Randomized Controlled Trial of a Cardiopulmonary Resuscitation Video in Advance Care Planning for Progressive Pancreas and Hepatobiliary Cancer Patients SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-06, 2012 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) ID OF-LIFE DISCUSSIONS; HOSPITALIZED-PATIENTS; ILL PATIENTS; DIRECTIVES; DETERMINANTS; PREFERENCES; PHYSICIANS; PROGNOSES; SUPPORT; COHORT AB Background: Cardiopulmonary resuscitation (CPR) is an important advance directive (AD) topic in patients with progressive cancer; however such discussions are challenging. Objective: This study investigates whether video educational information about CPR engenders broader advance care planning (ACP) discourse. Methods: Patients with progressive pancreas or hepatobiliary cancer were randomized to an educational CPR video or a similar CPR narrative. The primary end-point was the difference in ACP documentation one month posttest between arms. Secondary end-points included study impressions; pre- and post-intervention knowledge of and preferences for CPR and mechanical ventilation; and longitudinal patient outcomes. Results: Fifty-six subjects were consented and analyzed. Rates of ACP documentation (either formal ADs or documented discussions) were 40% in the video arm (12/30) compared to 15% in the narrative arm (4/26), OR=3.6 [95% CI: 0.9-18.0], p = 0.07. Post-intervention knowledge was higher in both arms. Posttest, preferences for CPR had changed in the video arm but not in the narrative arm. Preferences regarding mechanical ventilation did not change in either arm. The majority of subjects in both arms reported the information as helpful and comfortable to discuss, and they recommended it to others. More deaths occurred in the video arm compared to the narrative arm, and more subjects died in hospice settings in the video arm. Conclusions: This pilot randomized trial addressing downstream ACP effects of video versus narrative decision tools demonstrated a trend towards more ACP documentation in video subjects. This trend, as well as other video effects, is the subject of ongoing study. C1 [Epstein, Andrew S.; Chen, Ling Y.; Gary, Kristen A.; Li, Yuelin; Agre, Patricia; Levin, Tomer T.; Reidy, Diane L.; Meng, Raymond D.; Segal, Neil H.; Yu, Kenneth H.; Abou-Alfa, Ghassan K.; Janjigian, Yelena Y.; Kelsen, David P.; O'Reilly, Eileen M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Epstein, AS (reprint author), Mem Sloan Kettering Canc Ctr, Div Gastrointestinal Med Oncol, 300 E 66th St,Room 1013, New York, NY 10065 USA. EM epsteina@mskcc.org RI Levin, Tomer/D-2997-2016 OI Levin, Tomer/0000-0001-5054-5103 FU NCI NIH HHS [P30 CA008748] NR 34 TC 23 Z9 23 U1 5 U2 14 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 JUN PY 2013 VL 16 IS 6 BP 623 EP 631 DI 10.1089/jpm.2012.0524 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 155GW UT WOS:000319736900010 PM 23725233 ER PT J AU Rosenberg, AR Baker, KS Syrjala, KL Back, AL Wolfe, J AF Rosenberg, Abby R. Baker, K. Scott Syrjala, Karen L. Back, Anthony L. Wolfe, Joanne TI Promoting Resilience among Parents and Caregivers of Children with Cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CHILDHOOD-CANCER; PEDIATRIC ONCOLOGY; PSYCHOSOCIAL CARE; PSYCHOLOGICAL DISTRESS; INDIVIDUAL-DIFFERENCES; FAMILY RESILIENCE AB Background: Promoting resilience is an aspect of psychosocial care that affects patient and whole-family wellbeing. There is little consensus about how to define or promote resilience during and after pediatric cancer. Objectives: The aims of this study were (1) to review the resilience literature in pediatric cancer settings; (2) to qualitatively ascertain caregiver-reported perceptions of resilience; and (3) to develop an integrative model of fixed and mutable factors of resilience among family members of children with cancer, with the goal of enabling better study and promotion of resilience among pediatric cancer families. Methods: The study entailed qualitative analysis of small group interviews with eighteen bereaved parents and family members of children with cancer treated at Seattle Children's Hospital. Small-group interviews were conducted with members of each bereaved family. Participant statements were coded for thematic analysis. An integrative, comprehensive framework was then developed. Results: Caregivers' personal appraisals of the cancer experience and their child's legacy shape their definitions of resilience. Described factors of resilience include baseline characteristics (i.e., inherent traits, prior expectations of cancer), processes that evolve over time (i.e., coping strategies, social support, provider interactions), and psychosocial outcomes (i.e., post-traumatic growth and lack of psychological distress). These elements were used to develop a testable model of resilience among family members of children with cancer. Conclusions: Resilience is a complex construct that may be modifiable. Once validated, the proposed framework will not only serve as a model for clinicians, but may also facilitate the development of interventions aimed at promoting resilience in family members of children with cancer. C1 [Rosenberg, Abby R.; Baker, K. Scott] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Rosenberg, Abby R.; Baker, K. Scott; Syrjala, Karen L.; Back, Anthony L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rosenberg, Abby R.; Baker, K. Scott; Syrjala, Karen L.; Back, Anthony L.] Univ Washington, Seattle, WA 98195 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolfe, Joanne] Childrens Hosp, Boston, MA 02115 USA. [Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenberg, AR (reprint author), Seattle Childrens Hosp, Div Pediat Hematol Oncol, M-S MB 8-501,POB 5371, Seattle, WA 98105 USA. EM abby.rosenberg@seattlechildrens.org FU Ruth L. Kirschstein National Research Service Award [T32CA009351]; Conquer Cancer Foundation of ASCO Jane C. Wright Young Investigator Award; ASCO; Conquer Cancer Foundation Board of Directors FX Abby R. Rosenberg is a St. Baldrick's Foundation Fellow and was supported by the Ruth L. Kirschstein National Research Service Award T32CA009351 and a Conquer Cancer Foundation of ASCO Jane C. Wright Young Investigator Award, supported by the ASCO and the Conquer Cancer Foundation Board of Directors. Any opinions, findings, and conclusions expressed in this material are those of the authors and do not necessarily reflect those of the American Society of Clinical Oncology, the Conquer Cancer Foundation, or the ASCO and the Conquer Cancer Foundation Board of Directors. NR 53 TC 22 Z9 23 U1 6 U2 42 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 JUN PY 2013 VL 16 IS 6 BP 645 EP 652 DI 10.1089/jpm.2012.0494 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 155GW UT WOS:000319736900013 PM 23646887 ER PT J AU Smith, AK Thai, JN Bakitas, MA Meier, DE Spragens, LH Temel, JS Weissman, DE Rabow, MW AF Smith, Alexander K. Thai, Julie N. Bakitas, Marie A. Meier, Diane E. Spragens, Lynn H. Temel, Jennifer S. Weissman, David E. Rabow, Michael W. TI The Diverse Landscape of Palliative Care Clinics SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OUTPATIENT; CANCER; ONCOLOGY; CENTERS AB Background: Many health care organizations are interested in instituting a palliative care clinic. However, there are insufficient published data regarding existing practices to inform the development of new programs. Objective: Our objective was to obtain in-depth information about palliative care clinics. Methods: We conducted a cross-sectional survey of 20 outpatient palliative care practices in diverse care settings. The survey included both closed-and open-ended questions regarding practice size, utilization of services, staffing, referrals, services offered, funding, impetus for starting, and challenges. Results: Twenty of 21 (95%) practices responded. Practices self-identified as: hospital-based (n = 7), within an oncology division/cancer center (n = 5), part of an integrated health system (n = 6), and hospice-based (n = 2). The majority of referred patients had a cancer diagnosis. Additional common diagnoses included chronic obstructive pulmonary disease, neurologic disorders, and congestive heart failure. All practices ranked "pain management" and "determining goals of care" as the most common reasons for referrals. Twelve practices staffed fewer than 5 half-days of clinic per week, with 7 operating only one half-day per week. Practices were staffed by a mixture of physicians, advanced practice nurses or nurse practitioners, nurses, or social workers. Eighteen practices expected their practice to grow within the next year. Eleven practices noted a staffing shortage and 8 had a wait time of a week or more for a new patient appointment. Only 12 practices provide 24/7 coverage. Billing and institutional support were the most common funding sources. Most practices described starting because inpatient palliative providers perceived poor quality outpatient care in the outpatient setting. The most common challenges included: funding for staffing (11) and being overwhelmed with referrals (8). Conclusions: Once established, outpatient palliative care practices anticipate rapid growth. In this context, outpatient practices must plan for increased staffing and develop a sustainable financial model. C1 [Smith, Alexander K.; Thai, Julie N.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94941 USA. [Rabow, Michael W.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94941 USA. [Smith, Alexander K.; Thai, Julie N.] San Francisco VA Med Ctr, San Francisco, CA USA. [Bakitas, Marie A.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Sect Palliat Med, Dept Anesthesiol, Lebanon, NH 03766 USA. [Meier, Diane E.] Mt Sinai Med Ctr, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Spragens, Lynn H.] Spragens & Associates LLC, Durham, NC USA. [Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weissman, David E.] Med Coll Wisconsin, Palliat Care Ctr, Dept Internal Med, Milwaukee, WI 53226 USA. RP Smith, AK (reprint author), Univ Calif San Francisco, 4150 Clement St 181G, San Francisco, CA 94941 USA. EM aksmith@ucsf.edu OI Bakitas, Marie/0000-0002-2913-2053 FU National Center for Research Resources UCSF-CTSI [UL1 RR024131]; NINR [1R01NR011871-01] FX Dr. Smith was supported by the National Center for Research Resources UCSF-CTSI (UL1 RR024131). Marie A. Bakitas, APRN, DnSc, was support by NINR grant number 1R01NR011871-01. NR 9 TC 16 Z9 16 U1 1 U2 8 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 JUN PY 2013 VL 16 IS 6 BP 661 EP 668 DI 10.1089/jpm.2012.0469 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 155GW UT WOS:000319736900015 PM 23662953 ER PT J AU Qiu, JY Chen, WJ Gao, XF Xu, Y Tong, HQ Yang, M Xiao, ZP Yang, M AF Qiu, Jianyin Chen, Weijun Gao, Xiufei Xu, Yong Tong, Huiqi Yang, Min Xiao, Zeping Yang, Min TI A randomized controlled trial of group cognitive behavioral therapy for Chinese breast cancer patients with major depression SO JOURNAL OF PSYCHOSOMATIC OBSTETRICS AND GYNECOLOGY LA English DT Article DE Breast cancer; group cognitive behavioral therapy; major depression ID WOMEN; PREVALENCE; DISORDERS; SURVIVORS; INTERVENTION; SYMPTOMS; EFFICACY; ANXIETY AB Background: This study aims to evaluate the effects of Group Cognitive Behavioral Therapy (GCBT) in treating major depression in Chinese women with breast cancer. Methods: Sixty-two breast cancer patients diagnosed with major depression were randomly assigned to GCBT group (N=31) or a waiting list control group provided with an educational booklet (N=31). The primary outcome measure was the 17-Item Hamilton Depression Rating Scale (17-HAMD). The second outcome measures were Self-Rating Anxiety Scale, Functional Assessment of Cancer Therapy - Breast and Self-Esteem Scale (SES). Assessments were carried out at completion of the study and six-month afterwards. Results: Patients in the GCBT group had a significant reduction in the 17-HAMD mean score by 9 points (p<0.001), more than any reduction among patients in the control group from baseline to the end of therapy and a significant 7 points (p<0.001) more reduction from baseline to six-month follow-up. GCBT also yielded significantly greater improvement than the control group with regard to quality of life (QoL; p<0.01) and self-esteem (p<0.05). No significant differences were found between groups on improving anxiety (p>0.05). Conclusion: The results of this trial suggest that GCBT is effective for treating major depression, as well as for improving QoL and self-esteem in breast cancer patients. C1 [Qiu, Jianyin; Chen, Weijun; Xu, Yong; Xiao, Zeping] Shanghai Jiao Tong Univ, Dept Clin Psychol, Shanghai Mental Hlth Ctr, Sch Med, Shanghai 200030, Peoples R China. [Gao, Xiufei] Shanghai Univ TCM, Longhua Hosp, Dept Breast Care, Shanghai, Peoples R China. [Tong, Huiqi] San Francisco VA Med Ctr, Womens Clin, San Francisco, CA USA. [Yang, Min; Yang, Min] Univ Nottingham, Dept Psychiat, Nottingham NG7 2RD, England. RP Yang, M (reprint author), Univ Nottingham, Dept Psychiat, Univ Pk, Nottingham NG7 2RD, England. EM Min.Yang@nottingham.ac.uk FU WHO [WP/2006/CHN/MNH/2.4/001] FX This study was funded by grant number WP/2006/CHN/MNH/2.4/001 from WHO. NR 42 TC 8 Z9 10 U1 3 U2 26 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0167-482X J9 J PSYCHOSOM OBST GYN JI J. Psychosomat. Obstet. Gynecol. PD JUN PY 2013 VL 34 IS 2 BP 60 EP 67 DI 10.3109/0167482X.2013.766791 PG 8 WC Psychology, Clinical; Obstetrics & Gynecology; Psychiatry SC Psychology; Obstetrics & Gynecology; Psychiatry GA 155LB UT WOS:000319748300002 PM 23646866 ER PT J AU Appleton, KM Luttrell, LM AF Appleton, Kathryn M. Luttrell, Louis M. TI Emergent biological properties of arrestin pathway-selective biased agonism SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE Arrestin; functional genomics; functional selectivity; G protein-coupled receptor; heterotrimeric G protein; pharmacology ID PROTEIN-COUPLED RECEPTOR; PARATHYROID-HORMONE; BETA(2)-ADRENERGIC RECEPTOR; CRYSTAL-STRUCTURE; CARDIAC MYOCYTES; LIGAND EFFICACY; IN-VIVO; ACTIVATION; REVEALS; ALLOSTERISM AB Our growing appreciation of the pluridimensionality of G protein-coupled receptor ( GPCR) signaling, combined with the phenomenon of orthosteric ligand "bias'', has created the possibility of drugs that selectively modulate different aspects of GPCR function for therapeutic benefit. When viewed from the short-term perspective, e.g. changes in receptor conformation, effector coupling or second messenger generation, biased ligands appear to activate a subset of the response profile produced by a conventional agonist. Yet when examined in vivo, the limited data available suggest that biased ligand effects can diverge from their conventional counterparts in ways that cannot be predicted from their in vitro efficacy profile. What is currently missing, at least with respect to G protein and arrestin pathway-selective ligands, is a rational framework for relating the in vitro efficacy of a "biased'' agonist to its in vivo actions that will enable drug screening programs to identify ligands with the desired biological effects. C1 [Appleton, Kathryn M.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Coll Med, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Coll Med, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Luttrell, LM (reprint author), Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 CSB,MSC624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NIDDK NIH HHS [DK55524, DK64353] NR 34 TC 5 Z9 5 U1 0 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PD JUN PY 2013 VL 33 IS 3 BP 153 EP 161 DI 10.3109/10799893.2013.769004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 155LI UT WOS:000319749200005 PM 23448506 ER PT J AU Appleton, KM Lee, MH Alele, C Luttrell, DK Peterson, YK Luttrell, LM AF Appleton, Kathryn M. Lee, Mi-Hye Alele, Christine Luttrell, Deirdre K. Peterson, Yuri K. Luttrell, Louis M. TI DISSOCIATION OF ARRESTIN-DEPENDENT SIGNALING FROM RECEPTOR DESENSITIZATION USING FUNCTIONALLY-SELECTIVE PARATHYROID HORMONE RECEPTOR LIGANDS SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Meeting Abstract C1 [Appleton, Kathryn M.; Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Lee, Mi-Hye; Alele, Christine; Luttrell, Louis M.] Med Univ S Carolina, Dept Med & Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Deirdre K.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 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 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PD JUN PY 2013 VL 33 IS 3 BP 184 EP 184 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 155LI UT WOS:000319749200011 ER PT J AU Leonard, A Appleton, KM Luttrell, LM Peterson, YK AF Leonard, Anthony Appleton, Kathryn M. Luttrell, Louis M. Peterson, Yuri K. TI A HIGH-CONTENT, LIVE-CELL, AND REAL-TIME APPROACH TO THE QUANTITATION OF LIGAND INDUCED B-ARRESTIN2 AND CLASS A/CLASS B GPCR MOBILIZATION SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Meeting Abstract C1 [Leonard, Anthony; Appleton, Kathryn M.; Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med & Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 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 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PD JUN PY 2013 VL 33 IS 3 BP 199 EP 199 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 155LI UT WOS:000319749200057 ER PT J AU McDougle, CJ AF McDougle, Christopher J. TI Sounding a Wake-Up Call: Improving the Lives of Adults With Autism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [McDougle, Christopher J.] Massachusetts Gen Hosp, Lexington, MA 02421 USA. RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat & Pediat, 1 Maguire Rd, Lexington, MA 02421 USA. EM cmcdougle@partners.org NR 9 TC 4 Z9 4 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2013 VL 52 IS 6 BP 566 EP 568 DI 10.1016/j.jaac.2013.03.013 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 160UZ UT WOS:000320147300003 PM 23702444 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Lou Gehrig, Angelina Jolie, and Cancer Genetics 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. [Burstein, Harold J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 2 Z9 2 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2013 VL 11 IS 6 BP 631 EP 632 PG 2 WC Oncology SC Oncology GA 158MJ UT WOS:000319975400001 PM 23744861 ER PT J AU Kumar, P Moy, B AF Kumar, Pallavi Moy, Beverly TI Cancer Health Disparities and the Cost of Cancer Care: Payment Model Issues SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID AMERICAN SOCIETY; INSURANCE; MEDICAID; ASSOCIATION C1 [Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 13 TC 3 Z9 3 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2013 VL 11 IS 6 BP 633 EP 636 PG 4 WC Oncology SC Oncology GA 158MJ UT WOS:000319975400002 PM 23744862 ER PT J AU Ettinger, DS Akerley, W Borghaei, H Chang, AC Cheney, RT Chirieac, LR D'Amico, TA Demmy, TL Govindan, R Grannis, FW Grant, SC Horn, L Jahan, TM Komaki, R Kong, FM Kris, MG Krug, LM Lackner, RP Lennes, IT Loo, BW Martins, R Otterson, GA Patel, JD Pinder-Schenck, MC Pisters, KM Reckamp, K Riely, GJ Rohren, E Shapiro, TA Swanson, SJ Tauer, K Wood, DE Yang, SC Gregory, K Hughes, M AF Ettinger, David S. Akerley, Wallace Borghaei, Hossein Chang, Andrew C. Cheney, Richard T. Chirieac, Lucian R. D'Amico, Thomas A. Demmy, Todd L. Govindan, Ramaswamy Grannis, Frederic W., Jr. Grant, Stefan C. Horn, Leora Jahan, Thierry M. Komaki, Ritsuko Kong, Feng-Ming (Spring) Kris, Mark G. Krug, Lee M. Lackner, Rudy P. Lennes, Inga T. Loo, Billy W., Jr. Martins, Renato Otterson, Gregory A. Patel, Jyoti D. Pinder-Schenck, Mary C. Pisters, Katherine M. Reckamp, Karen Riely, Gregory J. Rohren, Eric Shapiro, Theresa A. Swanson, Scott J. Tauer, Kurt Wood, Douglas E. Yang, Stephen C. Gregory, Kristina Hughes, Miranda TI Non-Small Cell Lung Cancer, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID SUBSOLID PULMONARY NODULES; NEEDLE ASPIRATION; COMPUTED-TOMOGRAPHY; TOBACCO DEPENDENCE; FLEISCHNER-SOCIETY; UNITED-STATES; CT SCANS; EPIDEMIOLOGY; MANAGEMENT; MORTALITY AB These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail. C1 [Ettinger, David S.] Sidney Kimmel Comprehens Canc Ctr Johns Hop, Sidney, BC, Canada. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chang, Andrew C.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Chirieac, Lucian R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Grannis, Frederic W., Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Grant, Stefan C.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Horn, Leora] Univ Alabama, Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Jahan, Thierry M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahan, Thierry M.] UCSF Helen Diller Family, Comprehens Canc Ctr, San Francisco, CA USA. [Komaki, Ritsuko] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kong, Feng-Ming (Spring); Kris, Mark G.; Krug, Lee M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lackner, Rudy P.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Martins, Renato] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Patel, Jyoti D.] Solove Res Inst, Columbus, OH USA. [Pinder-Schenck, Mary C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Pinder-Schenck, Mary C.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Gregory, Kristina; Hughes, Miranda] Univ Tennessee, Inst Canc, Knoxville, TN 37996 USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hop, Sidney, BC, Canada. OI Chang, Andrew/0000-0001-9506-0425; Reckamp, Karen/0000-0002-9213-0325 FU Exelixis Inc.; Abraxis Oncology; Boehringer Ingelheim GmbH; Celgene Corporation; Genentech, Inc.; GlaxoSmithKline; Pfizer Inc; Pharmacyclics; Eli Lilly and Company; Eisai, Inc.; Millennium; Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Endo Pharmaceuticals and HealthTronics; Genentech; ARIAD Pharmaceuticals, Inc. FX Dr. Martins: PI for Bayer HealthCare; Eisai Inc.; Genentech, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer Inc. Receives research funding from Exelixis Inc.; Dr. Otterson: Receives research funding from Abraxis Oncology; Boehringer Ingelheim GmbH; Celgene Corporation; Genentech, Inc.; GlaxoSmithKline; Pfizer Inc; and Pharmacyclics. Consultant for Abraxis Bioscience, Inc. Advisory board member for Genentech, Inc.; Dr. Patel: Receives research funding from Eli Lilly and Company. Advisory board member for Genentech, Inc.; Supported by educational grants from Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; and ARIAD Pharmaceuticals, Inc. NR 36 TC 105 Z9 122 U1 3 U2 11 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 JUN PY 2013 VL 11 IS 6 BP 645 EP 653 PG 9 WC Oncology SC Oncology GA 158MJ UT WOS:000319975400004 PM 23744864 ER PT J AU Biermann, JS Adkins, DR Agulnik, M Benjamin, RS Brigman, B Butrynski, JE Cheong, D Chow, W Curry, WT Frassica, DA Frassica, FJ Hande, KR Hornicek, FJ Jones, RL Mayerson, J McGarry, SV McGrath, B Morris, CD O'Donnell, RJ Randall, RL Santana, VM Satcher, RL Siegel, HJ von Mehren, M Bergman, MA Sundar, H AF Biermann, J. Sybil Adkins, Douglas R. Agulnik, Mark Benjamin, Robert S. Brigman, Brian Butrynski, James E. Cheong, David Chow, Warren Curry, William T. Frassica, Deborah A. Frassica, Frank J. Hande, Kenneth R. Hornicek, Francis J. Jones, Robin L. Mayerson, Joel McGarry, Sean V. McGrath, Brian Morris, Carol D. O'Donnell, Richard J. Randall, R. Lor Santana, Victor M. Satcher, Robert L. Siegel, Herrick J. von Mehren, Margaret Bergman, Mary Anne Sundar, Hema TI Bone Cancer Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID GIANT-CELL TUMOR; SCANDINAVIAN-SARCOMA-GROUP; HIGH-GRADE OSTEOSARCOMA; TERM-FOLLOW-UP; POSITRON-EMISSION-TOMOGRAPHY; CORE NEEDLE-BIOPSY; CARBON ION RADIOTHERAPY; DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA; INTENSITY-MODULATED RADIOTHERAPY; SELECTIVE ARTERIAL EMBOLIZATION AB Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma. C1 [Biermann, J. Sybil] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Adkins, Douglas R.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Adkins, Douglas R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Agulnik, Mark] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Butrynski, James E.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cheong, David] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Chow, Warren] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Curry, William T.; Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Frassica, Deborah A.; Frassica, Frank J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Hande, Kenneth R.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jones, Robin L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Mayerson, Joel] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Mayerson, Joel] Solove Res Inst, Columbus, OH USA. [McGarry, Sean V.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [McGrath, Brian] Roswell Pk Canc Inst, Buffalo, NY USA. [Morris, Carol D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Santana, Victor M.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Siegel, Herrick J.] Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA. [Bergman, Mary Anne] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Biermann, JS (reprint author), Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. NR 236 TC 23 Z9 23 U1 0 U2 12 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 JUN PY 2013 VL 11 IS 6 BP 688 EP 723 PG 36 WC Oncology SC Oncology GA 158MJ UT WOS:000319975400008 PM 23744868 ER PT J AU Wachen, JS Shipherd, JC Suvak, M Vogt, D King, LA King, DW AF Wachen, Jennifer Schuster Shipherd, Jillian C. Suvak, Michael Vogt, Dawne King, Lynda A. King, Daniel W. TI Posttraumatic Stress Symptomatology as a Mediator of the Relationship Between Warzone Exposure and Physical Health Symptoms in Men and Women SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID GULF-WAR VETERANS; SEXUAL-HARASSMENT; PERCEIVED HEALTH; MILITARY PERSONNEL; COMBAT EXPOSURE; CHRONIC PAIN; DISORDER; ILLNESS; TRAUMA; SAMPLE AB The mediating role of posttraumatic stress symptomatology (PSS) on the association between warzone exposure and physical health symptoms in 7 bodily systems (cardiovascular, dermatological, gastrointestinal, genitourinary, musculoskeletal, neurological, and pulmonary) was examined. We also examined if mediation effects varied as a function of sex. A sample of 317 U. S. Gulf war veterans was assessed for warzone exposure, PSS, and physical health symptoms 10 years after deployment. PSS was significantly associated with postdeployment physical health in all symptom categories when accounting for predeployment health (with effect sizes ranging from a 1.27-1.64 increase in the likelihood of postdeployment physical health symptoms with a 1 standard deviation increase in the PSS symptoms). PSS severity mediated the relationship between warzone exposure and postdeployment symptoms in all physical health domains (with percent mediation ranging 44%-75%). A significant Warzone Exposure x PSS interaction emerged for 5 outcomes such that the effect of PSS on physical health was stronger for veterans reporting lower warzone exposure. No significant interactions with sex emerged. These findings suggest the important influence of PSS on physical health symptoms for both men and women. C1 [Wachen, Jennifer Schuster; Shipherd, Jillian C.; Suvak, Michael; Vogt, Dawne; King, Lynda A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Wachen, Jennifer Schuster; Shipherd, Jillian C.; Vogt, Dawne; King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. RP Wachen, JS (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM Jennifer.Wachen@va.gov NR 48 TC 4 Z9 4 U1 6 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2013 VL 26 IS 3 BP 319 EP 328 DI 10.1002/jts.21818 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 157GA UT WOS:000319882800003 PM 23695839 ER PT J AU Wolf, EJ Harrington, KM Reardon, AF Castillo, D Taft, CT Miller, MW AF Wolf, Erika J. Harrington, Kelly M. Reardon, Annemarie F. Castillo, Diane Taft, Casey T. Miller, Mark W. TI A Dyadic Analysis of the Influence of Trauma Exposure and Posttraumatic Stress Disorder Severity on Intimate Partner Aggression SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MALE VIETNAM VETERANS; INTERDEPENDENCE MODEL; RELATIONSHIP ABUSE; SYMPTOMS; PERPETRATION; SCALE; PTSD; ASSOCIATIONS; DISTRESS AB This study used structural equation modeling to evaluate a mediation model of the relationship between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and perpetration of intimate partner physical and psychological aggression in trauma-exposed veterans and their cohabitating spouses (n = 286 couples; 88% male veteran and female spouse, 80.8% White, non-Hispanic). Dyadic data analyses were used to simultaneously evaluate actor and partner effects using the actor-partner interdependence model (Kashy & Kenny, 2000). The primary hypothesis was that PTSD would mediate the association between trauma exposure and intimate partner physical and psychological aggression with these effects evident both within and across members of a couple (i.e., actor and partner effects). The best-fitting model included (a) equivalent actor and partner direct effects of trauma on veterans' acts of psychological aggression (beta = .17 to .20, p = .001), and (b) equivalent actor and partner indirect effects via PTSD on veterans' acts of physical aggression (beta = .08 to .10, p < .001). There were no direct or indirect effects predicting the spouses' aggression. Results suggest it is important to consider the trauma histories and possible presence of PTSD in both partners as this may be a point of intervention when treating distressed couples. C1 [Wolf, Erika J.; Reardon, Annemarie F.; Taft, Casey T.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wolf, Erika J.; Taft, Casey T.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Harrington, Kelly M.] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA. [Castillo, Diane] VA New Mexico Healthcare Syst, Albuquerque, NM USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU Intramural VA [CDA-2-067-10S]; NIMH NIH HHS [R01 MH079806] NR 47 TC 6 Z9 6 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2013 VL 26 IS 3 BP 329 EP 337 DI 10.1002/jts.21805 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 157GA UT WOS:000319882800004 PM 23636815 ER PT J AU Sripada, RK Rauch, SAM Tuerk, PW Smith, E Defever, AM Mayer, RA Messina, M Venners, M AF Sripada, Rebecca K. Rauch, Sheila A. M. Tuerk, Peter W. Smith, Erin Defever, Andrew M. Mayer, Rebecca A. Messina, Michael Venners, Margaret TI Mild Traumatic Brain Injury and Treatment Response in Prolonged Exposure for PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; RANDOMIZED CONTROLLED-TRIAL; THERAPY; VETERANS; IRAQ; METAANALYSIS; AFGHANISTAN; MECHANISMS; CLINICIAN AB A proportion of U.S. veterans returning from Iraq and Afghanistan have experienced mild traumatic brain injury (mTBI), which is associated with increased risk for developing posttraumatic stress disorder (PTSD). Prolonged Exposure (PE) has proven effectiveness in the treatment of PTSD; however, some clinicians have reservations about using PE with individuals with a history of mTBI. We examined the impact of PE for veterans with PTSD and with or without a history of mTBI in a naturalistic sample of 51 veterans who received PE at a Veterans Health Administration PTSD clinic. We also analyzed previously collected data from a controlled trial of 22 veterans randomly assigned to PE or present centered therapy. For both sets of data, we found that PE reduced symptom levels and we also did not detect an effect for mTBI, suggesting that PE may be helpful for individuals with PTSD and a history of mTBI. C1 [Sripada, Rebecca K.; Rauch, Sheila A. M.; Smith, Erin; Defever, Andrew M.; Mayer, Rebecca A.; Messina, Michael; Venners, Margaret] Univ Michigan, Sch Med, VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Tuerk, Peter W.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. RP Sripada, RK (reprint author), VA Serious Mental Illness Treatment Resource & Ev, Ann Arbor, MI USA. EM rekaufma@umich.edu RI Rauch, Sheila/K-4450-2015; OI Rauch, Sheila/0000-0001-9686-4011; Sripada, Rebecca/0000-0002-2844-3458 NR 48 TC 14 Z9 14 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2013 VL 26 IS 3 BP 369 EP 375 DI 10.1002/jts.21813 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 157GA UT WOS:000319882800009 PM 23696427 ER PT J AU Steenkamp, MM Litz, BT Dickstein, BD Salters-Pedneault, K Hofmann, SG AF Steenkamp, Maria M. Litz, Brett T. Dickstein, Benjamin D. Salters-Pedneault, Kristalyn Hofmann, Stefan G. TI What Is the Typical Response to Sexual Assault? Reply to Bonanno (2013) SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; RESILIENCE; TRAJECTORIES; TRAUMA; SYMPTOMS; INJURY; SURVIVORS; EVENTS; US AB We respond to Bonanno's (2013) comment on our longitudinal evaluation of sexual assault survivors. Bonanno posits that minor disruption in functioning is the modal response to any stressor or trauma, yet most women we studied had marked initial symptoms in the immediate months following assault, which gradually improved over time. We argue that sexual violence is one example of intentional and malicious victimization, which differs from other experiences studied by Bonanno, such as spinal cord injury. Our study also differed from most previous studies in that it specifically examined the acute reactions period, which is the only period that can distinguish between resilience and recovery: Both trajectories ultimately involve good adaptation, but are distinguished by the degree of initial postevent disruption. We address Bonanno's contention that our results should be dismissed on methodological and statistical grounds. Our findings suggest that prior research about the frequency of resilience may in part be confounded by the degree and type of stress exposure. C1 [Steenkamp, Maria M.; Litz, Brett T.; Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Steenkamp, Maria M.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Dickstein, Benjamin D.] VA Cincinnati Healthcare Syst, Cincinnati, OH USA. [Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT 06226 USA. RP Steenkamp, MM (reprint author), Boston Vet Affairs Med Ctr, 150 South Huntington Ave 13B-73, Boston, MA 02130 USA. EM maria.steenkamp2@va.gov RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 18 TC 1 Z9 1 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2013 VL 26 IS 3 BP 394 EP 396 DI 10.1002/jts.21804 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 157GA UT WOS:000319882800013 PM 23737299 ER PT J AU Hoban, R Bucher, S Neuman, I Chen, MH Tesfaye, N Spector, JM AF Hoban, Rebecca Bucher, Sherri Neuman, Ida Chen, Minghua Tesfaye, Neghist Spector, Jonathan M. TI 'Helping Babies Breathe' Training in Sub-Saharan Africa: Educational Impact and Learner Impressions SO JOURNAL OF TROPICAL PEDIATRICS LA English DT Article DE neonatal resuscitation; international child health; developing countries; educational intervention; neonatal mortality ID NEONATAL RESUSCITATION; SETTINGS AB Background: Poor resuscitation contributes significantly to neonatal deaths globally. Helping Babies Breathe (HBB) is a new evidence-based neonatal resuscitation curriculum for low-resource settings. Objective: We sought to characterize knowledge changes after national-level HBB training in Ethiopia, factors correlated with successful training, resuscitation skills and trainees' perceptions. Methods: Trainees completed multiple-choice questionnaires (MCQ) before and after a 2-day course. After training, bag-mask ventilation (BMV) skills were assessed and feedback questionnaires completed. Results: Resuscitation knowledge improved from 8.7/10 (SD 1.4) to 9.4/10 (SD 1.1; p = 0.003). Correct MCQ responses relating to essential aspects of resuscitation increased 68-79%. Pre-training knowledge differences between physicians and non-physicians disappeared. MCQ scores increased as trainer:trainee ratio decreased (p = 0.004). Mean post-HBB BMV scores [5.7/7 (SD 1.6)] were not impacted by trainer:trainee ratio. Conclusions: Ethiopian HBB training improved neonatal resuscitation knowledge and was well received. Lower trainer:trainee ratio was associated with increased MCQ scores. HBB eliminated baseline knowledge differences between Ethiopian healthworker cadres. C1 [Hoban, Rebecca] Rush Univ, Med Ctr, Dept Pediat, Div Neonatol, Chicago, IL 60612 USA. [Bucher, Sherri] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA. [Bucher, Sherri] Indiana Univ Sch Med, IU Kenya Program, Indianapolis, IN USA. [Chen, Minghua] Tufts Med Ctr, Div Newborn Med, Boston, MA USA. [Spector, Jonathan M.] Massachusetts Gen Hosp, Dept Neonatol, Boston, MA 02114 USA. [Spector, Jonathan M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hoban, R (reprint author), Rush Univ, Med Ctr, Dept Pediat, Div Neonatol, 1653 W Congress Pkwy,622 Murdock Bldg, Chicago, IL 60612 USA. EM Rebecca.hoban@gmail.com FU Laerdal Foundation FX We thank the Ethiopian MoH and all who contributed to HBB Ethiopia including Laerdal Foundation, UNICEF, Nalini Singhal, Jonathan Davis, Eileen Schoen and the AAP for permission to publish the HBB BMV test and modified MCQ test. The funding sponsors of HBB Ethiopia did not contribute to the study design, analysis or interpretation of the data. HBB trainers, some from funding partners, did assist in data collection during the training. Ida Neuman of UNICEF assisted with the writing of the manuscript. S.B.'s travel expenses to Ethiopia were supported by the Laerdal Foundation. All authors have made substantial contributions to (i) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (ii) drafting the article or revising it critically for important intellectual content and (3) final approval of the version to be submitted. Specifically, R. H., S. B. and J.S. contributed to the design of the study. R. H. performed the literature review. All authors except M. C. made significant contributions to data collection. M. C. performed the statistical analysis. R. H. wrote the bulk of the manuscript, with all authors contributing to editing of the manuscript. All authors approved the final manuscript. NR 12 TC 12 Z9 12 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0142-6338 J9 J TROP PEDIATRICS JI J. Trop. Pediatr. PD JUN PY 2013 VL 59 IS 3 BP 180 EP 186 DI 10.1093/tropej/fms077 PG 7 WC Pediatrics; Tropical Medicine SC Pediatrics; Tropical Medicine GA 156IE UT WOS:000319814500004 PM 23335632 ER PT J AU White, JM Mimiaga, MJ Reisner, SL Mayer, KH AF White, Jaclyn M. Mimiaga, Matthew J. Reisner, Sari L. Mayer, Kenneth H. TI HIV Sexual Risk Behavior among Black Men Who Meet Other Men on the Internet for Sex SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE MSM; Internet; African American/Black; HIV; Sexual risk ID AFRICAN-AMERICAN MEN; CAGE QUESTIONNAIRE; EVOLUTIONARY TREES; MAXIMUM-LIKELIHOOD; HIDDEN POPULATIONS; UNITED-STATES; CONDOM USE; MSM; PREVENTION; PARTNERS AB Using the Internet to meet sexual partners is associated with increased HIV risk behavior, including substance use, sex with multiple or anonymous partners, and unprotected anal sex (UAS), among diverse samples of MSM, yet little is known about Internet use and HIV risk among Black MSM specifically. In 2008, a sample of 197 Black MSM completed an interviewer-administered assessment and voluntary HIV counseling and testing. One fifth of the sample (20 %) reported meeting a sexual partner via the Internet in the past 12 months. Men who met sexual partners over the Internet had significantly more male sex partners (M = 13.44, SD = 20.01) than men who did not meet partners in this manner (M = 4.11, SD = 4.14, p < 0.001) and reported significantly higher rates of UAS (p < 0.05). Adjusting for sociodemographic and other HIV-related covariates, factors significantly associated with the increased odds of engaging in at least one episode of UAS with a male partner in the past 12 months included: meeting sexual partners on the Internet, identifying as gay, and lower knowledge about HIV transmission. These findings highlight the unique HIV risk behaviors among Black MSM meeting sexual partners via the Internet and warrant tailoring of prevention activities to address the specific behaviors and social influences that may contribute to increased HIV spread among this population. C1 [White, Jaclyn M.; Mimiaga, Matthew J.; Reisner, Sari L.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mmimiaga@partners.org FU HIV/AIDS Bureau, Massachusetts Department of Public Health FX This work was funded by the HIV/AIDS Bureau, Massachusetts Department of Public Health. NR 53 TC 12 Z9 12 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD JUN PY 2013 VL 90 IS 3 BP 464 EP 481 DI 10.1007/s11524-012-9701-y PG 18 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 154NQ UT WOS:000319683100008 PM 22689294 ER PT J AU Kim, SP Karnes, RJ Nguyen, PL Ziegenfuss, JY Han, LC Thompson, RH Trinh, QD Sun, M Boorjian, SA Beebe, TJ Tilburt, JC AF Kim, Simon P. Karnes, R. Jeffrey Nguyen, Paul L. Ziegenfuss, Jeanette Y. Han, Leona C. Thompson, R. Houston Quoc-Dien Trinh Sun, Maxine Boorjian, Stephen A. Beebe, Timothy J. Tilburt, Jon C. TI Clinical Implementation of Quality of Life Instruments and Prediction Tools for Localized Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; nomograms; urology; radiation oncology ID RADICAL PROSTATECTOMY; RESPONSE RATES; INDEX; MEN; VALIDATION; CARCINOMA; SURVIVORS; UPDATE; STAGE; CARE AB Purpose: Although clinical guidelines recommend assessing quality of life, cancer aggressiveness and life expectancy for making localized prostate cancer treatment decisions, it is unknown whether instruments that objectively measure such outcomes have disseminated into clinical practice. In this context we determined whether quality of life and prediction instruments for prostate cancer have been adopted by radiation oncologists and urologists in the United States. Materials and Methods: Using a nationally representative mail survey of 1,422 prostate cancer specialists in the United States, we queried about self-reported clinical implementation of quality of life instruments, prostate cancer nomograms and life expectancy prediction tools in late 2011. The Pearson chi-square test and multivariate logistic regression were used to determine differences in the use of each instrument by physician characteristics. Results: A total of 313 radiation oncologists and 328 urologists completed the survey for a 45% response rate. Although 55% of respondents reported using prostate cancer nomograms, only 27% and 23% reported using quality of life and life expectancy prediction instruments, respectively. On multivariate analysis urologists were less likely to use quality of life instruments than radiation oncologists (OR 0.40, p < 0.001). Physicians who spent 30 minutes or more counseling patients were consistently more likely to use quality of life instruments (OR 2.57, p < 0.001), prostate cancer nomograms (OR 1.83, p = 0.009) and life expectancy prediction tools (OR 1.85, p = 0.02) than those who spent less than 15 minutes. Conclusions: Although prostate cancer nomograms have been implemented into clinical practice to some degree, the use of quality of life and life expectancy tools has been more limited. Increased attention to implementing validated instruments into clinical practice may facilitate shared decision making for patients with prostate cancer. C1 [Kim, Simon P.; Karnes, R. Jeffrey; Thompson, R. Houston; Boorjian, Stephen A.] Mayo Clin, Dept Urol, Rochester, MN 55905 USA. [Han, Leona C.; Beebe, Timothy J.] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN 55905 USA. [Tilburt, Jon C.] Mayo Clin, Knowledge & Evaluat Unit, Rochester, MN 55905 USA. [Han, Leona C.; Tilburt, Jon C.] Mayo Clin, Biomed Eth Res Unit, Rochester, MN 55905 USA. [Ziegenfuss, Jeanette Y.] HealthPartners Inst Educ & Res, Minneapolis, MN USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Quoc-Dien Trinh; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Sun, Maxine] Univ Montreal, Ctr Hlth, Fac Med, Dept Publ Hlth, Montreal, PQ, Canada. RP Tilburt, JC (reprint author), Mayo Clin, Dept Internal Med, 200 1st St Southwest, Rochester, MN 55905 USA. EM tilburt.jon@mayo.edu FU Informed Medical Decisions Foundation Robert Derzon Award; Mayo Clinic Healthcare Delivery Research Scholars Program; Heritage Medical Research Institute-Prostate Cancer Foundation Young Investigator Award FX Supported by the Informed Medical Decisions Foundation Robert Derzon Award, Mayo Clinic Healthcare Delivery Research Scholars Program and Heritage Medical Research Institute-Prostate Cancer Foundation Young Investigator Award. NR 29 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2013 VL 189 IS 6 BP 2092 EP 2098 DI 10.1016/j.juro.2012.11.174 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 158PY UT WOS:000319985900022 PM 23219546 ER PT J AU Chuang, PY Fu, J He, JC AF Chuang, Peter Y. Fu, Jia He, John C. TI Capturing the in vivo molecular signature of the podocyte SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID GLOMERULI AB The podocyte has an essential role in glomerular function. When cultured ex vivo, podocytes do not recapitulate their in vivo phenotype. Several technical barriers have prevented isolation of podocytes from animals with sufficient yield and purity to allow genome-wide assessment of their molecular fingerprint. Boerries et al. overcame some of these barriers and characterized the transcriptome and proteome of freshly isolated podocytes. These data sets and isolation protocol are valuable resources for the podocyte research community. C1 [Chuang, Peter Y.; He, John C.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Fu, Jia] Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing 210008, Jiangsu, Peoples R China. [He, John C.] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. RP Chuang, PY (reprint author), Mt Sinai Sch Med, Dept Med, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU NIDDK NIH HHS [P01-DK56492, R01 DK088541, 5K08-DK082760, K08 DK082760, 1R01-DK088541, R01 DK078897, P01 DK056492] NR 9 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2013 VL 83 IS 6 BP 986 EP 988 DI 10.1038/ki.2013.65 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 155ID UT WOS:000319740300003 PM 23727999 ER PT J AU Friedman, AN Yu, ZS Tabbey, R Denski, C Tamez, H Wenger, J Thadhani, R Li, Y Watkins, BA AF Friedman, Allon N. Yu, Zhangsheng Tabbey, Rebeka Denski, Cheryl Tamez, Hector Wenger, Julia Thadhani, Ravi Li, Yong Watkins, Bruce A. TI Inverse relationship between long-chain n-3 fatty acids and risk of sudden cardiac death in patients starting hemodialysis SO KIDNEY INTERNATIONAL LA English DT Article DE fatty acids; hemodialysis; n-3; omega-3; sudden cardiac death ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; FISH-OIL SUPPLEMENTATION; UNITED-STATES; CARDIOVASCULAR EVENTS; TERM HEMODIALYSIS; DIALYSIS PATIENTS; CONTROLLED-TRIAL; DISEASE; BLOOD; OMEGA-3-FATTY-ACIDS AB Experimental and clinical evidence suggests that long-chain n-3 fatty acids may protect against sudden cardiac death, the leading cause of mortality in hemodialysis patients. Here we investigated whether long-chain n-3 fatty acids have a protective relationship with sudden cardiac death in 100 patients who died of sudden cardiac death during the first year of starting hemodialysis and 300 patients who survived. Individuals were selected from a nationally representative cohort of over 1000 US hemodialysis units in 2004-2005. The odds of sudden cardiac death were calculated by quartile of long-chain n-3 fatty acid levels over the first year. There was a significant inverse relationship between long-chain n-3 fatty acids and the risk of sudden cardiac death even after adjusting for relevant comorbid conditions, biochemical values, and dietary fats. The odds of sudden cardiac death at 1 year for the second, third, and fourth quartile groups of long-chain n-3 fatty acids were 0.37, 0.22, and 0.20, respectively, compared with the lowest quartile. This significant inverse relationship was maintained even during the highest-risk first few months on hemodialysis. Thus, long-chain n-3 fatty acids are strongly and independently associated with a lower risk of sudden cardiac death in hemodialysis patients throughout the first year of hemodialysis. C1 [Friedman, Allon N.] Indiana Univ Sch Med, Dept Med, Div Nephrol, Indianapolis, IN 46202 USA. [Yu, Zhangsheng; Tabbey, Rebeka; Denski, Cheryl] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Tamez, Hector; Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Li, Yong; Watkins, Bruce A.] Univ Connecticut, Dept Nutr Sci, Lipid Chem & Mol Biol Lab, Storrs, CT USA. RP Friedman, AN (reprint author), Indiana Univ Sch Med, Dept Med, Div Nephrol, 535 Barnhill Dr,RT 150R, Indianapolis, IN 46202 USA. EM allfried@iupui.edu FU National Institutes of Health [DK084403, DK094872, HL112746]; National Kidney Foundation FX ANF was supported by funding from the National Institutes of Health (DK084403) and the National Kidney Foundation. RT is supported by funding from the National Institutes of Health (DK094872, HL112746). NR 41 TC 12 Z9 12 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2013 VL 83 IS 6 BP 1130 EP 1135 DI 10.1038/ki.2013.4 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 155ID UT WOS:000319740300021 PM 23389417 ER PT J AU Bhensdadia, NM Hunt, KJ Lopes-Virella, MF Tucker, JM Mataria, MR Alge, JL Neely, BA Janech, MG Arthur, JM AF Bhensdadia, Nishant M. Hunt, Kelly J. Lopes-Virella, Maria F. Tucker, J. Michael Mataria, Mohammad R. Alge, Joseph L. Neely, Benjamin A. Janech, Michael G. Arthur, John M. CA Vet Affairs Diabet Trial VADT Stud TI Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE biological markers; chronic kidney disease; diabetes; diabetic nephropathy; type 2 diabetes; urine ID GELATINASE-ASSOCIATED LIPOCALIN; CLINICAL PROTEINURIA; GLUCOSE CONTROL; BLOOD-PRESSURE; RISK-FACTORS; MICROALBUMINURIA; NEPHROPATHY; COMPLICATIONS; INSUFFICIENCY; ALBUMINURIA AB Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary albumin to creatinine ratio is used as a predictor for the development of nephropathy but it is neither sensitive nor specific. Here we used liquid chromatography/mass spectrometry on urine of eight normoalbuminuric patients with type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss of renal function. Initial verification of seven markers (agrin, haptoglobin, mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and uromodulin) in the urine of an additional 30 patients showed that haptoglobin was the best predictor of early renal functional decline. We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio < 300mg/g). In comparing the highest to lowest tertiles, the odds ratio for having early renal function decline was 2.70 (CI: 1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI 1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance. Thus, the haptoglobin to creatinine ratio may be useful to predict patients with type 2 diabetes at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate. C1 [Bhensdadia, Nishant M.; Hunt, Kelly J.; Lopes-Virella, Maria F.; Tucker, J. Michael; Mataria, Mohammad R.; Alge, Joseph L.; Neely, Benjamin A.; Janech, Michael G.; Arthur, John M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.; Janech, Michael G.; Arthur, John M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, 829 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM arthurj@musc.edu OI Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066; Janech, Michael/0000-0002-3202-4811 FU Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; NIH [R01 DK080234, UL1 RR029882, ULI RR029882]; Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA Merit Review Award FX This study was supported by a merit review award (JMA) and a career development 2 award (MGJ) from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs and NIH grants R01 DK080234 and UL1 RR029882. The VADT study was sponsored by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. Portions of the data were presented in abstract form at the 2012 American Society of Nephrology meeting.; Sources of support that require acknowledgment:; VA Merit Review Award; NIH R01DK080234; ULI RR029882 NR 41 TC 19 Z9 23 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2013 VL 83 IS 6 BP 1136 EP 1143 DI 10.1038/ki.2013.57 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 155ID UT WOS:000319740300022 PM 23536133 ER PT J AU Merchant, ML Niewczas, MA Ficociello, LH Lukenbill, JA Wilkey, DW Li, M Khundmiri, SJ Warram, JH Krolewski, AS Klein, JB AF Merchant, Michael L. Niewczas, Monika A. Ficociello, Linda H. Lukenbill, Janice A. Wilkey, Daniel W. Li, Ming Khundmiri, Syed J. Warram, James H. Krolewski, Andrzej S. Klein, Jon B. TI Plasma kininogen and kininogen fragments are biomarkers of progressive renal decline in type 1 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE ACE inhibitors; diabetic nephropathy; mass spectrometry; microalbuminuria; proteomic analysis ID B2 RECEPTORS; BRADYKININ; MICROALBUMINURIA; NEPHROPATHY; MICE; MECHANISMS; PATHWAYS; INJURY; RISK AB The ability of microalbuminuria to predict early progressive renal function decline in type 1 diabetic patients has been questioned. To resolve this, we determined the plasma proteome differences between microalbuminuric patients with type 1 diabetes and stable renal function (controls) and patients at risk for early progressive renal function decline (cases) and asked whether these differences have value as surrogate biomarkers. Mass spectrometry was used to analyze small (< 3 kDa) plasma peptides isolated from well-matched case and control plasma obtained at the beginning of an 8-12 year follow-up period. A Spearman analysis of plasma peptide abundance and the rate of renal function decline during follow-up identified seven masses with a significant negative correlation with early progressive renal function decline. Tandem mass spectrometry identified three fragments of high-molecular-weight kininogen. Increased plasma high-molecular-weight kininogen in the cases was confirmed by immunoblot. One peptide, des-Arg9-BK(1-8), induced Erk1/2 phosphorylation when added apically to two proximal tubular cell lines grown on permeable inserts. Thus, we have identified plasma protein fragments, some of which have biological activity with moderate to strong correlation, with early progressive renal function decline in microalbuminuric patients with type 1 diabetes. Other peptides are candidates for validation as candidate biomarkers of diabetes-associated renal dysfunction. C1 [Merchant, Michael L.; Lukenbill, Janice A.; Wilkey, Daniel W.; Li, Ming; Khundmiri, Syed J.; Klein, Jon B.] Univ Louisville, Kidney Dis Program, Louisville, KY 40292 USA. [Merchant, Michael L.; Lukenbill, Janice A.; Wilkey, Daniel W.; Li, Ming; Khundmiri, Syed J.; Klein, Jon B.] Univ Louisville, Clin Prote Ctr, Louisville, KY 40292 USA. [Niewczas, Monika A.; Ficociello, Linda H.; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Klein, Jon B.] Vet Adm Med Ctr, Louisville, KY 40202 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Room 368,1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu; jon.klein@louisville.edu RI Merchant, Michael/F-7109-2013; Merchant, Michael/N-7444-2013 OI Merchant, Michael/0000-0003-4128-4057 FU National Institutes of Health [R01 DK067638, R01 DK041526]; Office of Research and Development, Medical Research Service, Department of Veterans Affairs; ADA [7-03-MN- 28, U01 DK085673-01, R01 DK091584-01A1]; DOE [DE-FG02-05ER6406] FX We thank Nina Lesousky for Technical Support regarding OK cells. This work was supported by National Institutes of Health grants R01 DK067638 (A.S.K. and J.B.K.), R01 DK041526 (A.S.K.), ADA Grant 7-03-MN- 28 (M.A.N.), U01 DK085673-01 (M.L.M. and J.B.K.), R01 DK091584-01A1 (M.L.M.), DOE DE-FG02-05ER6406 (J.B.K. and M.L.M.), and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (J.B.K.). NR 25 TC 11 Z9 11 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2013 VL 83 IS 6 BP 1177 EP 1184 DI 10.1038/ki.2013.8 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 155ID UT WOS:000319740300027 PM 23466993 ER PT J AU Huang, JM Mckee, M Huang, HD Xiang, A Davidson, AJ Lu, HAJ AF Huang, Jianmin Mckee, Mary Huang, Hong D. Xiang, Alice Davidson, Alan J. Lu, Hua A. J. TI A zebrafish model of conditional targeted podocyte ablation and regeneration SO KIDNEY INTERNATIONAL LA English DT Article DE ablation; kidney regeneration; nitroreductase; podocyte; zebrafish ID CHRONIC KIDNEY-DISEASE; TRANSGENIC ZEBRAFISH; IGA NEPHROPATHY; INJURY; GLOMERULOSCLEROSIS; PROTEINURIA; CELLS; NITROREDUCTASE; EXPRESSION; PRONEPHROS AB Podocytes are specialized cells that contribute critically to the normal structure and function of the glomerular filtration barrier. Their depletion plays an important role in the pathogenesis of glomerulosclerosis. Here, we report generation of a genetic model of conditional podocyte ablation and regeneration in zebrafish using a bacterial nitroreductase strategy to convert a prodrug, metronidazole, into a cytotoxic metabolite. A transgenic zebrafish line was generated that expresses green fluorescence protein (GFP) and the nitroreductase fusion protein under the control of the podocin promoter Tg(podocin: nitroreductase-GFP). Treatment of these transgenic zebrafish with metronidazole results in podocyte apoptosis, a loss of nephrin and podocin expression, foot process effacement, and a leaky glomerular filtration barrier. Following metronidazole washout, proliferating cells were detected in the glomeruli of recovering transgenic fish with a restoration of nitroreductase-GFP fluorescence, nephrin and podocin expression, a reestablishment of normal foot process architecture, and glomerular barrier function. Thus, our studies show that zebrafish podocytes are capable of regenerating following depletion, and establish the Tg(podocin: NTR-GFP) fish as a new model to study podocyte injury and repair. C1 [Huang, Jianmin; Mckee, Mary; Huang, Hong D.; Xiang, Alice; Lu, Hua A. J.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Ctr Syst Biol,Program Membrane Biol, Boston, MA 02114 USA. [Huang, Jianmin; Mckee, Mary; Huang, Hong D.; Xiang, Alice; Lu, Hua A. J.] Harvard Univ, Sch Med, Boston, MA USA. [Davidson, Alan J.] Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1, New Zealand. RP Lu, HAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Div Nephrol,Dept Med, CPZN 8150,185 Cambridge St, Boston, MA 02114 USA. EM Halu@partners.org FU NIH [DK075940, RO3 DK084295]; American Society of Nephrology (ASN); Center for Regenerative Medicine; Boston Area Diabetes and Endocrinology Research Center (NIH) [DK-57521]; Center for the Study of Inflammatory Bowel Disease (NIH) [DK-43351] FX We thank Dr Dennis Brown for assistance with electron microscopy analysis; Dr Yawei Kong for assistance with generating the constructs and transgenic zebrafish; Drs J Malicki, Lem (Tufts University, Boston), Tepass, and Silva-Gagliardi (University of Toronto, Canada) for providing anti-crumbs antibody (panCrb); and Dr Iain Drummond for assistance with image analysis of zebrafish and providing constructs for probe generation. We thank Renee Ethier and David Machon in the zebrafish facility at Massachusetts General Hospital for their dedicated support and Dr Patricia K Donahoe for providing support for image acquisition and analysis. Dr AJD is supported by the Rutherford Foundation, Marsden Fund, and the Auckland Medical Research Foundation. HJL is supported by NIH KO8 grant DK075940, NIH RO3 DK084295, and a Gottschalk research grant from the American Society of Nephrology (ASN). The zebrafish facility is supported by the Center for Regenerative Medicine (MGH). The Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (NIH DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (NIH DK-43351). NR 45 TC 13 Z9 16 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2013 VL 83 IS 6 BP 1193 EP 1200 DI 10.1038/ki.2013.6 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 155ID UT WOS:000319740300029 PM 23466998 ER PT J AU Freeman, MP Hirschberg, AM Wang, B Petrillo, LF Connors, S Regan, S Joffe, H Cohen, LS AF Freeman, Marlene P. Hirschberg, April M. Wang, Betty Petrillo, Laura F. Connors, Stephanie Regan, Susan Joffe, Hadine Cohen, Lee S. TI Duloxetine for major depressive disorder and daytime and nighttime hot flashes associated with the menopausal transition SO MATURITAS LA English DT Article DE Depression; Major depressive disorder; Menopause; Vasomotor symptoms; Hot flashes; Anxiety ID SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; PERIMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; DOUBLE-BLIND; EFFICACY; MOOD AB Background: We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety. Methods: After a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n=19) received eight weeks of open-label treatment with duloxetine (60 mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7). Results: Of 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for >= 1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14-18), and 6.5 (IQR 4-11.5), respectively, reflecting a significant decrease (p=.0006). The response and remission rates were 56.3% (all responders were also remitters, having >= 50% decrease in HAM-D scores and final scores <= 7). Anxiety improved with treatment (p=.012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p=.009 and p=.008, respectively). Daytime but not nighttime hot flashes improved significantly. Conclusions: These data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Freeman, Marlene P.; Wang, Betty; Petrillo, Laura F.; Joffe, Hadine; Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Hirschberg, April M.; Connors, Stephanie; Regan, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, 185 Cambridge St, Boston, MA 02114 USA. EM mfreeman@partners.org OI Regan, Susan/0000-0003-0940-2017 FU Lilly FX This study was an Investigator Initiated Trial funded by Lilly. The sponsor had no input in the study design, implementation, or data analysis. NR 32 TC 3 Z9 3 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD JUN PY 2013 VL 75 IS 2 BP 170 EP 174 DI 10.1016/j.maturitas.2013.03.007 PG 5 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 160WG UT WOS:000320150600013 PM 23602542 ER PT J AU Courville, EL Wu, Y Kourda, J Roth, CG Brockmann, J Muzikansky, A Fathi, AT de Leval, L Orazi, A Hasserjian, RP AF Courville, Elizabeth L. Wu, Yue Kourda, Jihen Roth, Christine G. Brockmann, Jillian Muzikansky, Alona Fathi, Amir T. de Leval, Laurence Orazi, Attilio Hasserjian, Robert P. TI Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia SO MODERN PATHOLOGY LA English DT Article DE acute myeloid leukemia; chronic myelomonocytic leukemia; cytogenetics ID MYELODYSPLASIA-RELATED CHANGES; PROGNOSTIC SCORING SYSTEM; CYTOGENETIC ABNORMALITIES; MULTILINEAGE DYSPLASIA; RETROSPECTIVE ANALYSIS; NPM1 MUTATIONS; CLASSIFICATION; PROPOSALS; FEATURES; HISTORY AB Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P < 0.01) and less likely to receive aggressive treatment (P = 0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P = 0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases. C1 [Courville, Elizabeth L.; Brockmann, Jillian; Muzikansky, Alona; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Yue; Orazi, Attilio] Weill Cornell Med Coll, Dept Pathol, New York, NY USA. [Kourda, Jihen; de Leval, Laurence] Inst Univ Pathol, Lausanne, Switzerland. [Roth, Christine G.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Fathi, Amir T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 244, Boston, MA 02114 USA. EM rhasserjian@partners.org NR 42 TC 6 Z9 6 U1 1 U2 6 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 JUN PY 2013 VL 26 IS 6 BP 751 EP 761 DI 10.1038/modpathol.2012.218 PG 11 WC Pathology SC Pathology GA 156EY UT WOS:000319805800001 PM 23307061 ER PT J AU Krings, G Ramachandran, R Jain, D Wu, TT Yeh, MM Torbenson, M Kakar, S AF Krings, Gregor Ramachandran, Rageshree Jain, Dhanpat Wu, Tsung-Teh Yeh, Matthew M. Torbenson, Michael Kakar, Sanjay TI Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma SO MODERN PATHOLOGY LA English DT Article DE arginase; cholangiocarcinoma; glypican 3; scirrhous hepatocellular carcinoma ID TISSUE MICROARRAY ANALYSIS; LIVER-TRANSPLANTATION; INTRAHEPATIC CHOLANGIOCARCINOMA; CYTOKERATIN-19 EXPRESSION; HEPATOCYTE PARAFFIN-1; METASTATIC CARCINOMA; NEOPLASTIC TISSUES; ONCOFETAL PROTEIN; NEEDLE-BIOPSY; MARKER AB Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma-associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26% and 74%, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11%; P<0.001), cytokeratin 19 (26 vs 2%; P<0.001), and cytokeratin 7 (53 vs 2%; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80% of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79% and 85% of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100% sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting. C1 [Krings, Gregor; Ramachandran, Rageshree; Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Jain, Dhanpat] Yale Univ, Dept Pathol, New Haven, CT USA. [Wu, Tsung-Teh] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Yeh, Matthew M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Torbenson, Michael] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Kakar, Sanjay] Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. RP Kakar, S (reprint author), San Francisco VA Med Ctr, Dept Anat Pathol, 4150 Clement St, San Francisco, CA 94121 USA. EM sanjay.kakar@ucsf.edu FU Department of Pathology, University of California, San Francisco FX The study was funded by the Department of Pathology, University of California, San Francisco. NR 50 TC 16 Z9 18 U1 0 U2 3 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 JUN PY 2013 VL 26 IS 6 BP 782 EP 791 DI 10.1038/modpathol.2012.243 PG 10 WC Pathology SC Pathology GA 156EY UT WOS:000319805800004 PM 23348905 ER PT J AU Osborn, MJ Starker, CG McElroy, AN Webber, BR Riddle, MJ Xia, L DeFeo, AP Gabriel, R Schmidt, M von Kalle, C Carlson, DF Maeder, ML Joung, JK Wagner, JE Voytas, DF Blazar, BR Tolar, J AF Osborn, Mark J. Starker, Colby G. McElroy, Amber N. Webber, Beau R. Riddle, Megan J. Xia, Lily DeFeo, Anthony P. Gabriel, Richard Schmidt, Manfred von Kalle, Christof Carlson, Daniel F. Maeder, Morgan L. Joung, J. Keith Wagner, John E. Voytas, Daniel F. Blazar, Bruce R. Tolar, Jakub TI TALEN-based Gene Correction for Epidermolysis Bullosa SO MOLECULAR THERAPY LA English DT Article ID ZINC-FINGER NUCLEASES; DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS; STEM-CELLS; THERAPY; TARGET; EFFECTORS; VECTORS; DESIGN; KERATINOCYTES AB Recessive dystrophic epidermolysis bullosa (RDEB) is characterized by a functional deficit of type VII collagen protein due to gene defects in the type VII collagen gene (COL7A1). Gene augmentation therapies are promising, but run the risk of insertional mutagenesis. To abrogate this risk, we explored the possibility of using engineered transcription activator-like effector nucleases (TALEN) for precise genome editing. We report the ability of TALEN to induce site-specific double-stranded DNA breaks (DSBs) leading to homology-directed repair (HDR) from an exogenous donor template. This process resulted in COL7A1 gene mutation correction in primary fibroblasts that were subsequently reprogrammed into inducible pluripotent stem cells and showed normal protein expression and deposition in a teratoma-based skin model in vivo. Deep sequencing-based genome-wide screening established a safety profile showing on-target activity and three off-target (OT) loci that, importantly, were at least 10 kb from a coding sequence. This study provides proof-of-concept for TALEN-mediated in situ correction of an endogenous patient-specific gene mutation and used an unbiased screen for comprehensive TALEN target mapping that will cooperatively facilitate translational application. C1 [Osborn, Mark J.; McElroy, Amber N.; Webber, Beau R.; Riddle, Megan J.; Xia, Lily; DeFeo, Anthony P.; Wagner, John E.; Blazar, Bruce R.; Tolar, Jakub] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Osborn, Mark J.; Starker, Colby G.; Carlson, Daniel F.; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Starker, Colby G.; Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Gabriel, Richard; Schmidt, Manfred; von Kalle, Christof] Natl Ctr Tumor Dis, Dept Translat Oncol, Heidelberg, Germany. [Gabriel, Richard; Schmidt, Manfred; von Kalle, Christof] German Canc Res Ctr, Heidelberg, Germany. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tolar, J (reprint author), Univ Minnesota, Sch Med, MMC 366,420 Delaware St SE, Minneapolis, MN 55455 USA. EM tolar003@umn.edu OI Tolar, Jakub/0000-0002-0957-4380 FU Epidermolysis Bullosa Research Fund; Jackson Gabriel Silver Foundation; DebRA International; University of Minnesota Academic Health Center; Pioneering Unique Cures for Kids foundation; Children's Cancer Research Fund; Minneapolis; Minnesota; United States of America Department of Defense; National Institutes of Health [R01 GM098861]; National Institutes of Health Director's Pioneer Award [DP1 OD006862]; Jim and Ann Orr MGH Research Scholar Award; National Science Foundation FX This study was supported in part by grants from Epidermolysis Bullosa Research Fund, Jackson Gabriel Silver Foundation, DebRA International, University of Minnesota Academic Health Center, Pioneering Unique Cures for Kids foundation, Children's Cancer Research Fund, Minneapolis, Minnesota, and the United States of America Department of Defense. D. F. V. was supported by National Institutes of Health (R01 GM098861). J.K.J. was supported by a National Institutes of Health Director's Pioneer Award DP1 OD006862, and the Jim and Ann Orr MGH Research Scholar Award. M. L. M was supported by a National Science Foundation Graduate Research Fellowship. D. F. V. is a listed inventor on a patent application titled "TAL effector-mediated DNA modification," which is co-owned by Iowa State Univ. and the Univ. of Minnesota, and has been licensed to Cellectis, a European biotechnology company. J.K.J. has a financial interest in Transposagen Biopharmaceuticals. J.K.J.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. The other authors declare no conflict of interest. NR 49 TC 109 Z9 116 U1 6 U2 49 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 JUN PY 2013 VL 21 IS 6 BP 1151 EP 1159 DI 10.1038/mt.2013.56 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156YB UT WOS:000319859000009 PM 23546300 ER PT J AU Lee, YK Cowan, CA AF Lee, Youn-Kyoung Cowan, Chad A. TI White to brite adipocyte transition and back again SO NATURE CELL BIOLOGY LA English DT Editorial Material ID BROWN ADIPOSE-TISSUE; FAT; OBESITY; ADULTS; CELLS; MICE AB Identification and characterization of a third type of adipocyte known as brite (brown-in-white) adipocytes has drawn considerable attention, as these cells are thought to regulate energy expenditure and may help combat obesity. Remarkably, white adipocytes can adopt the characteristics of brite adipocytes following cold stimulation, and this process is reversible in vivo. C1 [Lee, Youn-Kyoung] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Lee, YK (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM ccowan@fas.harvard.edu NR 14 TC 9 Z9 9 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2013 VL 15 IS 6 BP 568 EP 569 PG 2 WC Cell Biology SC Cell Biology GA 156EM UT WOS:000319804200005 PM 23728463 ER PT J AU Settembre, C De Cegli, R Mansueto, G Saha, PK Vetrini, F Visvikis, O Huynh, T Carissimo, A Palmer, D Klisch, TJ Wollenberg, AC Di Bernardo, D Chan, L Irazoqui, JE Ballabio, A AF Settembre, Carmine De Cegli, Rossella Mansueto, Gelsomina Saha, Pradip K. Vetrini, Francesco Visvikis, Orane Tuong Huynh Carissimo, Annamaria Palmer, Donna Klisch, Tiemo Juergen Wollenberg, Amanda C. Di Bernardo, Diego Chan, Lawrence Irazoqui, Javier E. Ballabio, Andrea TI TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop SO NATURE CELL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; LYSOSOMAL BIOGENESIS; NETWORK REVEALS; GENE-EXPRESSION; TRANSGENIC MICE; PPAR-ALPHA; AUTOPHAGY; COACTIVATORS; FIBROBLAST-GROWTH-FACTOR-21 AB The lysosomal autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc 1 alpha and Ppar 1 alpha. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism. C1 [Settembre, Carmine; De Cegli, Rossella; Mansueto, Gelsomina; Carissimo, Annamaria; Di Bernardo, Diego; Ballabio, Andrea] Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy. [Settembre, Carmine; Vetrini, Francesco; Tuong Huynh; Palmer, Donna; Klisch, Tiemo Juergen; Ballabio, Andrea] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Settembre, Carmine; Vetrini, Francesco; Tuong Huynh; Klisch, Tiemo Juergen; Ballabio, Andrea] Texas Children Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Settembre, Carmine; Ballabio, Andrea] Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy. [Saha, Pradip K.; Chan, Lawrence] Baylor Coll Med, Dept Med, Diabet & Endocrinol Res Ctr, Div Diabet,Dept Pediat, Houston, TX 77030 USA. [Visvikis, Orane; Wollenberg, Amanda C.; Irazoqui, Javier E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02115 USA. [Di Bernardo, Diego] Univ Naples Federico II, Dept Syst & Comp Sci, I-80125 Naples, Italy. [Chan, Lawrence] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Chan, Lawrence] Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA. [Chan, Lawrence] St Lukes Episcopal Hosp, Houston, TX 77030 USA. RP Settembre, C (reprint author), Telethon Inst Genet & Med TIGEM, Via Pietro Castellino 111, I-80131 Naples, Italy. EM settembre@tigem.it; ballabio@tigem.it RI di Ronza, Alberto/H-7674-2016; VISVIKIS, ORANE/N-1818-2016; OI di Ronza, Alberto/0000-0002-9813-5143; VISVIKIS, ORANE/0000-0001-7719-5836; Irazoqui, Javier/0000-0001-6553-1329; SETTEMBRE, Carmine/0000-0002-5829-8589; BALLABIO, Andrea/0000-0003-1381-4604; di Bernardo, Diego/0000-0002-1911-7407 FU Italian Telethon Foundation [TGM11CB6, TGM11SB1]; Beyond Batten Disease Foundation; European Research Council [250154]; March of Dimes [6-FY11-306]; US National Institutes of Health [R01-NS078072, R01-HL51586]; Diabetes and Endocrinology Research Center [P30-DK079638]; Mouse Metabolism Core at Baylor College of Medicine; Cancer Prevention and Research Institute of Texas [RP110390]; Fund for Medical Discovery postdoctoral fellowship from the Massachusetts General Hospital; National Institute of General Medical Sciences of the National Institutes of Health [R01GM101056-01] FX We thank G. Karsenty, D. Moore, H. Zoghbi, S. Colamarino, E. Abrams, D. Sabatini and R. Zoncu for critical reading of the manuscript. We thank G. Diez-Roux for critical reading of the manuscript, helpful discussions and support in manuscript preparation. We are also grateful to D. Medina, C. Spampanato and F. Annunziata for their contribution. We thank A. Soukas for help with the oil red O staining of C. elegans. We acknowledge the support of the Italian Telethon Foundation grant numbers TGM11CB6 (C.S., R.D.C. and A.B) and TGM11SB1 (A.C. and D.D.B.); the Beyond Batten Disease Foundation (C.S., F.V., T.H. and A.B.); European Research Council Advanced Investigator grant no. 250154 (A.B.); March of Dimes #6-FY11-306 (A.B.); US National Institutes of Health (R01-NS078072) (A.B.). This work was supported in part by grants from the US National Institutes of Health (R01-HL51586) to L.C. and the Diabetes and Endocrinology Research Center (P30-DK079638, L.C.) and the Mouse Metabolism Core (P.K.S.) at Baylor College of Medicine. T.J.K. is in part supported by the Cancer Prevention and Research Institute of Texas (RP110390). O.V. was funded by a Fund for Medical Discovery postdoctoral fellowship from the Massachusetts General Hospital. This study was funded in part by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM101056-01 to J.E.I. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 56 TC 152 Z9 158 U1 4 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2013 VL 15 IS 6 BP 647 EP + DI 10.1038/ncb2718 PG 23 WC Cell Biology SC Cell Biology GA 156EM UT WOS:000319804200015 PM 23604321 ER PT J AU O'Rourke, EJ Ruvkun, G AF O'Rourke, Eyleen J. Ruvkun, Gary TI MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability SO NATURE CELL BIOLOGY LA English DT Article ID PROTEIN SUBCELLULAR-LOCALIZATION; CAENORHABDITIS-ELEGANS; C. ELEGANS; LIFE-SPAN; LYSOSOMAL BIOGENESIS; LIPID-METABOLISM; GENE-EXPRESSION; FAT; HOMEOSTASIS; STARVATION AB Fat is stored or mobilized according to food availability. Malfunction of the mechanisms that ensure this coordination underlie metabolic diseases in humans. In mammals, lysosomal and autophagic function is required for normal fat storage and mobilization in the presence or absence of food. Autophagy is tightly linked to nutrients. However, if and how lysosomal lipolysis is coupled to nutritional status remains to be determined. Here we identify MXL-3 and HLH-30 as transcriptional switches coupling lysosomal lipolysis and autophagy to nutrient availability and controlling fat storage and ageing in Caenorhabditis elegans. Transcriptional coupling of lysosomal lipolysis and autophagy to nutrients is also observed in mammals. Thus, MXL-3 and HLH-30 orchestrate an adaptive and conserved cellular response to nutritional status and regulate lifespan. C1 [O'Rourke, Eyleen J.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [O'Rourke, Eyleen J.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM eorourke@molbio.mgh.harvard.edu; ruvkun@molbio.mgh.harvard.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU Human Frontiers Science Program Postdoctoral fellowship; [R01DK070147]; [K99DK087928] FX We thank members of the Ruvkun, Ausubel and Kaplan laboratories for helpful comments, especially S. Curran, A. Lee-Conery and M. Wang for help with longevity experiments, J. Larkins-Ford for carrying out Biosort analyses, J. Xu for help with qRT-PCR experiments, J. Bai for acquiring confocal microscopy images, and J. Melo, C. Danna and A. Frand for helpful reading of the manuscript. We are grateful to R. Niedra, B. Seed, Y. Namiki and M. Oettinger for sharing expertise and reagents for mammalian experiments, and thanks H. Y. Mak, A. Soukas, M. Van Gilst, M. Freeman, A. Saghatelian and A. Tyler for protocols, access to equipment and discussions on lipid measurements. We are also grateful to A. Mah and D. Baillie for generating some transgenic strains used early in this project but not presented here, and thank N. Martinez and M. Walhout for sharing reagents and expertise on yeast one-hybrid experiments. We would like to thank the National Bioresource Project, the C. elegans Genetics Center, C. Bargmann and G. Hermann for strains. E.J.O'R. was a recipient of a Human Frontiers Science Program Postdoctoral fellowship. This work was supported by grants R01DK070147 to G.R. and K99DK087928 to E.J.O'R. NR 33 TC 73 Z9 88 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2013 VL 15 IS 6 BP 668 EP + DI 10.1038/ncb2741 PG 20 WC Cell Biology SC Cell Biology GA 156EM UT WOS:000319804200017 PM 23604316 ER PT J AU Diaz, LA Polyak, K AF Diaz, Luis A., Jr. Polyak, Kornelia TI Tracking tumor resistance using 'liquid biopsies' SO NATURE MEDICINE LA English DT Editorial Material ID CANCER; PLASMA; CELLS; DNA AB Cancers are known to evolve in response to therapy, which may result in drug resistance. However, following this process in patients is challenging, as repeated biopsies of tumor tissue involves invasive procedures and tumor heterogeneity confounds interpretation of analyses. A recent study by Murtaza et al. 1 describes an approach to trace the genomic evolution of tumors in response to therapy by sampling circulating cell-free tumor DNA (ctDNA) from patient plasma at different time points during treatment. This strategy allowed the authors to detect mutations associated with therapy resistance. We asked three experts to comment on this study and its implications for studying and treating tumors in the clinic. C1 [Diaz, Luis A., Jr.] Johns Hopkins, Swim Across Amer Lab, Baltimore, MD 21218 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Diaz, LA (reprint author), Johns Hopkins, Swim Across Amer Lab, Baltimore, MD 21218 USA. NR 14 TC 1 Z9 1 U1 5 U2 33 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 JUN PY 2013 VL 19 IS 6 BP 676 EP 677 DI 10.1038/nm.3233 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 158OK UT WOS:000319981600014 ER PT J AU Krop, IE AF Krop, Ian E. TI TARGETED THERAPIES HER2-positive breast cancer-sifting through many good options SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID TRASTUZUMAB PLUS DOCETAXEL; PHASE-3 TRIAL; LAPATINIB; MULTICENTER AB The addition of lapatinib to paclitaxel improves survival in patients with newly diagnosed HER2-positive metastatic breast cancer, further validating the importance of HER2 signalling as a target in this cancer subtype. However, the availability of other more-effective and less-toxic HER2-targeted therapies limits the clinical usefulness of the regimen. C1 Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Krop, IE (reprint author), Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ikrop@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JUN PY 2013 VL 10 IS 6 BP 312 EP 313 DI 10.1038/nrclinonc.2013.72 PG 3 WC Oncology SC Oncology GA 152VU UT WOS:000319560300004 PM 23629473 ER PT J AU Ning, MM Lopez, M Sarracino, D Cao, J Karchin, M McMullin, D Wang, X Buonanno, FS Lo, EH AF Ning, M. M. Lopez, M. Sarracino, D. Cao, J. Karchin, M. McMullin, D. Wang, X. Buonanno, F. S. Lo, E. H. TI Pharmaco-proteomics opportunities for individualizing neurovascular treatment SO NEUROLOGICAL RESEARCH LA English DT Review DE Patent foramen ovale (PFO)-related stroke; Proteomics; Cardiac arrest; Therapeutic hypothermia; Thrombolysis ID PATENT FORAMEN OVALE; ACUTE ISCHEMIC-STROKE; HOSPITAL CARDIAC-ARREST; FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; BLOOD-BRAIN-BARRIER; INTERNATIONAL LIAISON COMMITTEE; AMERICAN-HEART-ASSOCIATION; EVALUATION TRIAL EPITHET; THERAPEUTIC HYPOTHERMIA AB Neurovascular disease often involves multi-organ system injury. For example, patent foramen ovale (PFO) related ischemic strokes involve not just the brain, but also the heart, the lung, and the peripheral vascular circulation. For higher-risk but high-reward systemic therapy (e.g., thrombolytics, therapeutic hypothermia (TH), PFO closure) to be implemented safely, very careful patient selection and close monitoring of disease progression and therapeutic efficacy are imperative. For example, more than a decade after the approval of therapeutic hypothermic and intravenous thrombolysis treatments, they both remain extremely underutilized, in part due to lack of clinical tools for patient selection or to follow therapeutic efficacy. Therefore, in understanding the complexity of the global effects of clinical neurovascular diseases and their therapies, a systemic approach may offer a unique perspective and provide tools with clinical utility. Clinical proteomic approaches may be promising to monitor systemic changes in complex multi-organ diseases - especially where the disease process can be 'sampled' in clinically accessible fluids such as blood, urine, and CSF. Here, we describe a 'pharmaco-proteomic' approach to three major challenges in translational neurovascular research directly at bedside - in order to better stratify risk, widen therapeutic windows, and explore novel targets to be validated at the bench - (i) thrombolytic treatment for ischemic stroke, (ii) therapeutic hypothermia for post-cardiac arrest syndrome, and (iii) treatment for PFO related paradoxical embolic stroke. In the future, this clinical proteomics approach may help to improve patient selection, ensure more precise clinical phenotyping for clinical trials, and individualize patient treatment. C1 [Ning, M. M.; Lopez, M.; Sarracino, D.; Cao, J.; Karchin, M.; McMullin, D.; Buonanno, F. S.; Lo, E. H.] Massachusetts Gen Hosp, Dept Neurol, Clin Prote Res Ctr, Boston, MA 02114 USA. [Ning, M. M.; Lopez, M.; Sarracino, D.; Cao, J.; Karchin, M.; McMullin, D.; Wang, X.; Buonanno, F. S.; Lo, E. H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ning, M. M.; Wang, X.; Buonanno, F. S.; Lo, E. H.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Lopez, M.; Sarracino, D.] Thermo Fisher BRIMS, Cambridge, MA USA. RP Ning, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,ACC-739C, Boston, MA 02114 USA. EM ning@hms.harvard.edu; lo@helix.mgh.harvard.edu RI Wang, Xiangdong/F-2913-2014 FU NIH/NINDS [R01 NS067139, P01-NS55104] FX This work was supported by the NIH/NINDS: R01 NS067139 (Ning) and P01-NS55104 (Lo). NR 138 TC 10 Z9 10 U1 0 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0161-6412 EI 1743-1328 J9 NEUROL RES JI Neurol. Res. PD JUN PY 2013 VL 35 IS 5 BP 448 EP 456 DI 10.1179/1743132813Y.0000000213 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156IY UT WOS:000319816500003 PM 23711324 ER PT J AU Duong, TQ AF Duong, Timothy Q. TI Magnetic resonance imaging of perfusion-diffusion mismatch in rodent and non-human primate stroke models SO NEUROLOGICAL RESEARCH LA English DT Review DE Magnetic resonance imaging; Perfusion-diffusion mismatch; Apparent diffusion coefficient; Cerebral blood flow; Diffusion-weighted imaging; Perfusion-weighted imaging; Experimental stroke model; Rodents; Oxygen challenge; Predictive mode; Rats; Hyperperfusion; Functional magnetic resonance imaging ID ISCHEMIC TISSUE FATE; CEREBRAL-BLOOD-FLOW; QUANTITATIVE PREDICTION; PLASMINOGEN ACTIVATOR; FOCAL ISCHEMIA; FUNCTIONAL MRI; BRAIN-INJURY; RAT-BRAIN; BASE-LINE; BOLD AB Stroke is a leading cause of death and long-term disability. Non-invasive magnetic resonance imaging (MRI) has been widely used for the early detection of ischemic stroke and the longitudinal monitoring of novel treatment strategies. Recent advances in MRI techniques have enabled improved sensitivity and specificity to detecting ischemic brain injury and monitoring functional recovery. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study experimental stroke in rats and non-human primates. C1 [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA. RP Duong, TQ (reprint author), Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NIH [R01-NS45879]; American Heart Association [EIA 0940104N, SDG 0830293N] FX This work was supported by the NIH (R01-NS45879) and the American Heart Association (EIA 0940104N and SDG 0830293N). NR 46 TC 2 Z9 2 U1 0 U2 4 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD JUN PY 2013 VL 35 IS 5 BP 465 EP 469 DI 10.1179/1743132813Y.0000000211 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156IY UT WOS:000319816500005 PM 23594679 ER PT J AU Beacham, BL Deatrick, JA AF Beacham, Barbara L. Deatrick, Janet A. TI Health Care Autonomy in Children with Chronic Conditions Implications for Self-Care and Family Management SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE Child; Development; Chronic health conditions; Family management; Self-care; Autonomy ID CHRONIC ILLNESS; ADOLESCENT AUTONOMY; CHILDHOOD; PERSPECTIVES; PERCEPTIONS; ADHERENCE; SUPPORT; IMPACT; STYLE AB Health care autonomy typically occurs during late adolescence but health care providers and families often expect children with chronic health conditions to master self-care earlier. Few studies have examined the development of health care autonomy as it pertains to self-care and family management. This review links the 3 concepts and discusses the implications for families and health care providers. Case studies are provided as exemplars to highlight areas where intervention and research is needed. C1 [Beacham, Barbara L.; Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Beacham, BL (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Room 243 2Lower Claire M Fagin Hall,418 Curie Blv, Philadelphia, PA 19104 USA. EM blynne@nursing.upenn.edu FU National Institutes of Health, National Institute of Nursing Research [F31NR11524, T32NR007100]; Sigma Theta Tau Xi Chapter, University of Pennsylvania FX This work was supported by grant nos. F31NR11524 and T32NR007100 from the National Institutes of Health, National Institute of Nursing Research and by a grant from the Sigma Theta Tau Xi Chapter, University of Pennsylvania. NR 27 TC 4 Z9 6 U1 2 U2 22 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 2013 VL 48 IS 2 BP 305 EP + DI 10.1016/j.cnur.2013.01.010 PG 14 WC Nursing SC Nursing GA 158FJ UT WOS:000319954600010 PM 23659815 ER PT J AU Hebert, PL McBean, AM O'Connor, H Frank, B Good, C Maciejewski, ML AF Hebert, Paul L. McBean, Alexander Marshall O'Connor, Heidi Frank, Barbara Good, Charles Maciejewski, Matthew L. TI Time until incident dementia among Medicare beneficiaries using centrally acting or non-centrally acting ACE inhibitors SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE dementia; hypertension; centrally active; ACE inhibitor; Alzheimer's; Medicare; pharmacoepidemiology ID CONVERTING ENZYME-INHIBITORS; ALZHEIMERS-DISEASE; INSTRUMENTAL VARIABLES; PRESCRIBING PREFERENCE; COGNITIVE IMPAIRMENT; PROSPECTIVE COHORT; PROPENSITY-SCORE; ANGIOTENSIN; PERINDOPRIL; PERFORMANCE AB Background Centrally active (CA) angiotensin-converting enzyme inhibitors (ACEIs) are able to cross the blood-brain barrier. Small observational studies and mouse models suggest that use of CA versus non-CA ACEIs is associated with a reduced incidence of Alzheimer's disease and related dementias (ADRD). Objective The aim of this research was to assess the effect of CA versus non-CA ACEI use on incident ADRD. Design This is a retrospective cohort study with a non-equivalent control group. Setting and patients This study used a national random sample of Medicare beneficiaries enrolled in Part D with an ACEI prescription. A prevalent ACEI user cohort included beneficiaries (n=107179) with an ACEI prescription prior to 30 April 2007; beneficiaries without an ACEI prescription before this date were defined as incident ACEI users (n=9840). Measurements The main outcome was time until first diagnosis of ADRD in Medicare claims. Results The unadjusted, propensity-matched and instrumental variable analyses of both the prevalent and incident ACEI user cohorts consistently showed similar time until incident ADRD in those taking CA ACEIs compared with those who took non-CA ACEIs. Limitations The limitations of this study include the use of observational data, relatively short follow-up time and claims-based measure of cognitive decline. Conclusions In this analysis of Medicare beneficiaries who were prevalent or incident users of ACEIs in 2007-2009, the use of CA ACEIs was unrelated to cognitive decline within 3years of index prescription. Continued follow-up of these patients and more sensitive measures of cognitive decline are necessary to determine whether a cognitive benefit of CA ACEIs is realized in the long term. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Hebert, Paul L.] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Hebert, Paul L.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [McBean, Alexander Marshall; O'Connor, Heidi; Frank, Barbara; Good, Charles] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Div Gen Internal Med, Dept Med, Durham, NC 27705 USA. RP Maciejewski, ML (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27705 USA. EM mlm34@duke.edu FU Centers for Medicare and Medicaid Services (CMS) [HHSM-500-2005-00271]; VA Health Services Research and Development Service (HSR&D) Research Career Scientist Award [RCS-10-391] FX This project was supported by the Centers for Medicare and Medicaid Services (CMS) contract HHSM-500-2005-00271. Dr. Maciejewski is supported by a VA Health Services Research and Development Service (HSR&D) Research Career Scientist Award (RCS-10-391). NR 29 TC 6 Z9 7 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2013 VL 22 IS 6 BP 641 EP 648 DI 10.1002/pds.3449 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 157DG UT WOS:000319875400010 PM 23620414 ER PT J AU Chan, ED Chan, MM Chan, MM AF Chan, Edward D. Chan, Michael M. Chan, Mallory M. TI Pulse oximetry: Understanding its basic principles facilitates appreciation of its limitations SO RESPIRATORY MEDICINE LA English DT Review DE Pulse oximetry; Oxygen saturation; Co-oximetry; Carboxyhemoglobin; Methemoglobin ID DECREASED OXYGEN-SATURATION; SICKLE-CELL-DISEASE; NAIL POLISH; HEMOGLOBIN KOLN; ANEMIA; SULFHEMOGLOBINEMIA; DESATURATION; ACCURACY; READINGS; BLOOD AB Pulse oximetry has revolutionized the ability to monitor oxygenation in a continuous, accurate, and non-invasive fashion. Despite its ubiquitous use, it is our impression and supported by studies that many providers do not know the basic principles behind its mechanism of function. This knowledge is important because it provides the conceptual basis of appreciating its Limitations and recognizing when pulse oximeter readings may be erroneous. In this review, we discuss how pulse oximeters are able to distinguish oxygenated hemoglobin from deoxygenated hemoglobin and how they are able to recognize oxygen saturation only from the arterial compartment of blood. Based on these principles, we discuss the various conditions that can cause spurious readings and the mechanisms underlying them. Published by Elsevier Ltd. C1 [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Chan, Michael M.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Chan, Mallory M.] Univ Colorado, Denver Sch Med, Aurora, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 55 TC 24 Z9 26 U1 8 U2 50 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUN PY 2013 VL 107 IS 6 BP 789 EP 799 DI 10.1016/j.rmed.2013.02.004 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 155ZO UT WOS:000319789700001 PM 23490227 ER PT J AU Chervin, RD Chesson, AL Benca, RM Greenough, GP O'Hearn, DJ Auckley, DH Littner, M Mullington, JM Malhotra, A Berry, RB Malhotra, RK Schulman, DA AF Chervin, Ronald D. Chesson, Andrew L., Jr. Benca, Ruth M. Greenough, Glen P. O'Hearn, Daniel J. Auckley, Dennis H. Littner, Michael Mullington, Janet M. Malhotra, Atul Berry, Richard B. Malhotra, Raman K. Schulman, David A. TI Organization and Structure for Sleep Medicine Programs at Academic Institutions: Part 1-Current Challenges SO SLEEP LA English DT Editorial Material ID DISORDERS; CENTERS C1 [Chervin, Ronald D.] Univ Michigan, Dept Neurol, Sleep Disorders Ctr, Ann Arbor, MI 48109 USA. [Chesson, Andrew L., Jr.] Louisiana State Univ, Sch Med, Dept Neurol, Div Sleep Med, Shreveport, LA USA. [Benca, Ruth M.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Greenough, Glen P.] Dartmouth Hitchcock Med Ctr, Sleep Disorders Ctr, Lebanon, NH 03766 USA. [O'Hearn, Daniel J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Auckley, Dennis H.] MetroHlth Med Ctr, Div Pulm Crit Care & Sleep Med, Cleveland, OH USA. [Auckley, Dennis H.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Littner, Michael] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. [Mullington, Janet M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA. [Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA. [Berry, Richard B.] Univ Florida, Gainesville, FL USA. [Malhotra, Raman K.] SLUcare Sleep Disorders Ctr, St Louis, MO USA. [Schulman, David A.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA. RP Chervin, RD (reprint author), Univ Michigan, Sleep Disorders Ctr, Michael S Aldrich Sleep Disorders Lab, C728 Med Inn Bldg,1500 East Med Ctr Dr, Ann Arbor, MI 48109 USA. FU NHLBI NIH HHS [R01 HL085188, R01 HL090897, K24 HL093218] NR 10 TC 0 Z9 0 U1 1 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUN 1 PY 2013 VL 36 IS 6 BP 795 EP 801 DI 10.5665/sleep.2690 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 155HX UT WOS:000319739700001 PM 23729918 ER PT J AU Chesson, AL Chervin, RD Benca, RM Greenough, GP O'Hearn, DJ Auckley, DH Littner, M Mullington, JM Malhotra, A Berry, RB Malhotra, RK Schulman, DA AF Chesson, Andrew L., Jr. Chervin, Ronald D. Benca, Ruth M. Greenough, Glen P. O'Hearn, Daniel J. Auckley, Dennis H. Littner, Michael Mullington, Janet M. Malhotra, Atul Berry, Richard B. Malhotra, Raman K. Schulman, David A. TI Organization and Structure for Sleep Medicine Programs at Academic Institutions: Part 2-Goals and Strategies to Optimize Patient Care, Education, and Discovery SO SLEEP LA English DT Editorial Material C1 [Chesson, Andrew L., Jr.] Louisiana State Univ, Sch Med, Dept Neurol, Div Sleep Med, Shreveport, LA USA. [Chervin, Ronald D.] Univ Michigan, Dept Neurol, Sleep Disorders Ctr, Ann Arbor, MI USA. [Benca, Ruth M.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Greenough, Glen P.] Dartmouth Hitchcock Med Ctr, Sleep Disorders Ctr, Lebanon, NH 03766 USA. [O'Hearn, Daniel J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Auckley, Dennis H.] MetroHlth Med Ctr, Div Pulm Crit Care & Sleep Med, Cleveland, OH USA. [Auckley, Dennis H.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Littner, Michael] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. [Mullington, Janet M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA. [Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA. [Berry, Richard B.] Univ Florida, Gainesville, FL USA. [Malhotra, Raman K.] SLUcare Sleep Disorders Ctr, St Louis, MO USA. [Schulman, David A.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA. RP Chesson, AL (reprint author), LSUHSC, Sch Med, 1501 Kings Highway,POB 33932, Shreveport, LA 71130 USA. FU NHLBI NIH HHS [K24 HL093218, R01 HL085188, R01 HL090897] NR 3 TC 0 Z9 0 U1 0 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUN 1 PY 2013 VL 36 IS 6 BP 803 EP 811 DI 10.5665/sleep.2692 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 155HX UT WOS:000319739700002 PM 23729919 ER PT J AU Hyder, O Hatzaras, I Sotiropoulos, GC Paul, A Alexandrescu, S Marques, H Pulitano, C Barroso, E Clary, BM Aldrighetti, L Ferrone, CR Zhu, AX Bauer, TW Walters, DM Groeschl, R Gamblin, TC Marsh, JW Nguyen, KT Turley, R Popescu, I Hubert, C Meyer, S Choti, MA Gigot, JF Mentha, G Pawlik, TM AF Hyder, Omar Hatzaras, Ioannis Sotiropoulos, Georgios C. Paul, Andreas Alexandrescu, Sorin Marques, Hugo Pulitano, Carlo Barroso, Eduardo Clary, Bryan M. Aldrighetti, Luca Ferrone, Cristina R. Zhu, Andrew X. Bauer, Todd W. Walters, Dustin M. Groeschl, Ryan Gamblin, T. Clark Marsh, J. Wallis Nguyen, Kevin T. Turley, Ryan Popescu, Irinel Hubert, Catherine Meyer, Stephanie Choti, Michael A. Gigot, Jean-Francois Mentha, Gilles Pawlik, Timothy M. TI Recurrence after operative management of intrahepatic cholangiocarcinoma SO SURGERY LA English DT Article; Proceedings Paper CT 65th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO) CY MAR 21-24, 2012 CL Orlando, FL SP Soc Surg Oncol (SSO) ID PROGNOSTIC-FACTORS; SURGICAL RESECTION; PREDICTIVE FACTORS; SURGERY; SURVIVAL; RADIOTHERAPY AB Introduction. Data on recurrence after operation for intrahepatic cholarigiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC. Methods. We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrencefree survival (RFS) were analyzed. Results. During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepdtic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size cm (H.R., 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. Conclusion. Recurrence after operative intervention for ICC was common. Disease recurred both at intraand extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence. C1 [Hyder, Omar; Hatzaras, Ioannis; Choti, Michael A.; Pawlik, Timothy M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Sotiropoulos, Georgios C.; Paul, Andreas] Univ Hosp Essen, Dept Surg, Essen, Germany. [Alexandrescu, Sorin; Popescu, Irinel] Inst Digest Dis & Liver Transplantat Fundeni, Bucharest, Romania. [Marques, Hugo; Barroso, Eduardo] Curry Cabral Hosp, Dept Surg, Lisbon, Portugal. [Pulitano, Carlo; Aldrighetti, Luca] Univ Milan, Osped San Raffaele, Dept Surg, I-20127 Milan, Italy. [Clary, Bryan M.; Turley, Ryan] Duke Med Ctr, Dept Surg, Durham, NC USA. [Ferrone, Cristina R.; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bauer, Todd W.] Univ Virginia, Dept Surg, Charlottesville, VA USA. [Walters, Dustin M.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Groeschl, Ryan; Gamblin, T. Clark] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Marsh, J. Wallis; Nguyen, Kevin T.; Hubert, Catherine; Gigot, Jean-Francois] Clin Univ St Luc, Dept Surg, B-1200 Brussels, Belgium. [Meyer, Stephanie; Mentha, Gilles] Hop Univ Geneve, Dept Surg, Geneva, Switzerland. RP Pawlik, TM (reprint author), Dept Surg, Div Surg Oncol, Blalock 688,600 N Wolfe St, Baltimore, MD 21287 USA. EM tpawlik1@jhmi.edu RI Hyder, Omar/D-1441-2013; POPESCU, IRINEL/B-3048-2008 OI Hyder, Omar/0000-0002-0965-5543; FU NCI NIH HHS [P30 CA006973] NR 31 TC 42 Z9 45 U1 0 U2 16 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2013 VL 153 IS 6 BP 811 EP 818 PG 8 WC Surgery SC Surgery GA 157JC UT WOS:000319891400009 PM 23499016 ER PT J AU Upadhyaya, P Smith, R Swift, UM Warshaw, AL Harken, AH AF Upadhyaya, Pooja Smith, Randi Swift, Upasna Mini Warshaw, Andrew L. Harken, Alden H. TI Mentoring for global health missions SO SURGERY LA English DT Editorial Material C1 [Upadhyaya, Pooja] Mobilizing Hlth, San Francisco, CA USA. [Smith, Randi] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Swift, Upasna Mini] Alameda Cty Med Ctr, Dept Med, Oakland, CA USA. [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Harken, Alden H.] Univ Calif, Dept Surg, Oakland, CA 94602 USA. RP Harken, AH (reprint author), Univ Calif, Dept Surg, 1411 E 31st St, Oakland, CA 94602 USA. EM aharken@acmedctr.org NR 5 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2013 VL 153 IS 6 BP 866 EP 870 DI 10.1016/j.surg.2013.01.002 PG 5 WC Surgery SC Surgery GA 157JC UT WOS:000319891400016 PM 23489941 ER PT J AU Shonka, N Piao, Y Gilbert, M Yung, A Chang, S DeAngelis, LM Lassman, AB Liu, J Cloughesy, T Robins, HI Lloyd, R Chen, A Prados, M Wen, PY Heymach, J de Groot, J AF Shonka, Nicole Piao, Yuji Gilbert, Mark Yung, Alfred Chang, Susan DeAngelis, Lisa M. Lassman, Andrew B. Liu, Jun Cloughesy, Timothy Robins, H. Ian Lloyd, Rita Chen, Alice Prados, Michael Wen, Patrick Y. Heymach, John de Groot, John TI Cytokines associated with toxicity in the treatment of recurrent glioblastoma with aflibercept SO TARGETED ONCOLOGY LA English DT Article DE Glioblastoma; Aflibercept; VEGF; Cytokines; Toxicity ID ADVANCED SOLID TUMORS; GROWTH-FACTOR TRAP; CELL LUNG-CANCER; PHASE-II; RADIOTHERAPY; BIOMARKERS; INHIBITOR; SUNITINIB; AXITINIB; PROSTATE AB Plasma profiling of patients treated with antiangiogenic agents may identify markers that correlate with toxicity. Objectives were to correlate changes in cytokine and angiogenic factors as potential markers of toxicity to aflibercept. Circulating cytokine and angiogenic factors were measured in 28 patients with recurrent glioblastoma in a single-arm phase II study of aflibercept. Plasma samples were analyzed at baseline, 24 h, and 28 days using multiplex assays or ELISA. We evaluated log-transformed baseline biomarker expressions with Cox proportional hazard regression models to assess the effect of markers on any grade II-IV (Gr II-IV) toxicity, on-target toxicity (hypertension, proteinuria, thromboembolism), and fatigue. All tests were two sided with a statistical significance level of p = 0.05. Among 28 pts, there were 116 Gr II-IV events. Changes in IL-13 from baseline to 24 h predicted on-target toxicities. Increases in IL-1b, IL-6, and IL-10 at 24 h were significantly associated with fatigue. Progression-free survival was 14.9 months for patients in the all-toxicity group and 9.0 months for patients in the on-target toxicity group compared to 4.3 months for those who did not develop any Gr II-IV toxicity (p = 0.002 and p = 0.045, respectively). Toxicity from antiangiogenic therapy remains an important cause of antiangiogenic treatment discontinuation and patient morbidity. Changes in IL6, IL10, and IL13 were repeatedly correlated with toxicity. Profiling of IL-13 as a surrogate for endothelial dysfunction could individualize patients at risk during antiangiogenic therapy, as could identifying those at higher risk for fatigue using IL-6 and IL-10. C1 [Shonka, Nicole] Univ Nebraska Med Ctr, Div Oncol & Hematol, Omaha, NE 68198 USA. [Piao, Yuji; Gilbert, Mark; Yung, Alfred; Liu, Jun; Heymach, John; de Groot, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chang, Susan; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lassman, Andrew B.] New York Presbyterian Columbia Univ, Dept Neurol, New York, NY 10032 USA. [Lassman, Andrew B.] New York Presbyterian Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Robins, H. Ian; Lloyd, Rita] Univ Wisconsin, Sch Med, Madison, WI 53792 USA. [Chen, Alice] NCI, NIH, Bethesda, MD 20892 USA. [Chen, Alice] CTEP, Bethesda, MD USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shonka, N (reprint author), Univ Nebraska Med Ctr, Div Oncol & Hematol, Omaha, NE 68198 USA. EM nshonka@unmc.edu FU National Institutes of Health [U01-CA62399, 1R21A126127]; ASCO FX Funding was received from the National Institutes of Health [U01-CA62399 to NABTC, 1R21A126127 to J. de G.] and the ASCO Career Development Award [to J. de G.]. NR 34 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 EI 1776-260X J9 TARGET ONCOL JI Target. Oncol. PD JUN PY 2013 VL 8 IS 2 BP 117 EP 125 DI 10.1007/s11523-013-0254-0 PG 9 WC Oncology SC Oncology GA 155VN UT WOS:000319776600005 PM 23345034 ER PT J AU Sujoy, V Pinto, A Nose, V AF Sujoy, Victoria Pinto, Andre Nose, Vania TI Columnar Cell Variant of Papillary Thyroid Carcinoma: A Study of 10 Cases with Emphasis on CDX2 Expression SO THYROID LA English DT Article ID AGGRESSIVE VARIANT; MARKER; CANCER; TUMORS; BRAF AB Background: Columnar cell variant is a recognized rare variant of papillary thyroid carcinoma (PTC) that has an uncertain clinical course. This variant has two subvariants, and one is regarded as a more aggressive form in comparison to the more common classical and follicular variants. These tumors have morphological resemblance with endometrial or colonic adenocarcinoma. CDX2, a transcription factor of the caudal homeobox family, plays a key role in intestinal development and differentiation, and it is widely used as a marker to detect adenocarcinomas of intestinal and colonic origin. CDX2 has been rarely reported in PTC. Methods: We studied 10 cases of columnar cell variant of PTC (CCV-PTC). The histological, architectural, and cytological features fulfilled the diagnostic criteria of the CCV-PTC, as defined by the current World Health Organization classification. Ten patients (six men and four women) ranging in age from 32 to 90 years (mean, 58.3 years) presented with tumors classified as indolent (four cases) or aggressive (six cases); three harbored a BRAF(V600E) mutation. All cases were beta-catenin negative. The Ki-67 proliferative index was up to 50%. All cases were thyroid transcription factor-1-positive. Using paraffin-embedded blocks, immunohistochemistry for CDX2 was performed to evaluate the reactivity of this antibody to this variant of PTC. Results: Nuclear positivity for CDX2 was detected in one out of the 10 cases studied (10%); the other nine cases did not express CDX2. Conclusion: Only one of our cases showed nuclear positivity for CDX2. Therefore, our study failed to confirm it as a marker for CCV-PTC. The absence of CDX2 in the majority of the cases does not support the theory of CDX2 playing a role in the intestinal phenotype of these tumors. C1 [Sujoy, Victoria; Pinto, Andre] Univ Miami, Dept Pathol, Miami, FL USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Nose, V (reprint author), Massachusetts Gen Hosp, Warren 214 55 Fruit St, Boston, MA 02114 USA. EM vnose@partners.org NR 23 TC 4 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUN PY 2013 VL 23 IS 6 BP 714 EP 719 DI 10.1089/thy.2012.0455 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 159GB UT WOS:000320032500011 PM 23488912 ER PT J AU Pretorius, E Vermeulen, N Bester, J Lipinski, B Kell, DB AF Pretorius, Etheresia Vermeulen, Natasha Bester, Janette Lipinski, Boguslaw Kell, Douglas B. TI A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE Ferric iron; iron chelation; platelet rich plasma; purified fibrinogen; scanning electron microscopy ID LABILE PLASMA IRON; PERIPHERAL ARTERIAL-DISEASE; NONTRANSFERRIN-BOUND IRON; INDUCED OXIDATIVE STRESS; ALZHEIMERS-DISEASE; AORTIC INTIMA; CARDIOVASCULAR-DISEASES; MAGNETIC-RESONANCE; PARKINSONS-DISEASE; DIABETES-MELLITUS AB Aims: Inflammatory diseases associated with iron overload are characterized by a changed coagulation profile, where there is a persistent presence of fibrin-like material of dense-matted deposits (DMDs). It is believed that one source of such material is a result of the activation of blood coagulation without the generation of thrombin, causing clots to become resistant to fibrinolytic dissolution. The aim of the current manuscript therefore is to apply a novel scanning electron microscopy method for assessing the role of functional chelation in the prevention or reversal of iron-induced fibrin formation. Methods and results: Purified fibrinogen and platelet-rich plasma were exposed to chelating agents followed by iron, to determine the chelating effects. We show that there is another, pathological pathway of fibrin formation initiated by free iron (initially as Fe (III)), leading to the formation of highly reactive oxygen species such as the hydroxyl radical that can oxidize and insolubilize proteins, a process that might be inhibited by iron-chelating compounds. The final product of such a pathway is a fibrin-like material, termed DMDs that are remarkably resistant to proteolytic degradation. Conclusions: Scanning electron microscopy shows that iron-chelating agents are effective inhibitors of DMD formation. The most active inhibitors of DMD formation proved to be Desferal, Clioquinol and Curcumin, whereas Epigallocatechin gallate and Deferiprone were less effective. The functional model we describe may point the clinical utility of various substances in iron-mediated degenerative diseases. C1 [Pretorius, Etheresia; Vermeulen, Natasha; Bester, Janette] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Kell, Douglas B.] Univ Manchester, Sch Chem, Manchester, Lancs, England. [Kell, Douglas B.] Univ Manchester, Manchester Inst Biotechnol, Manchester, Lancs, England. RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa. EM resia.pretorius@up.ac.za OI Kell, Douglas/0000-0001-5838-7963 NR 76 TC 19 Z9 19 U1 1 U2 14 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6516 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD JUN PY 2013 VL 23 IS 5 BP 352 EP 359 DI 10.3109/15376516.2012.762082 PG 8 WC Toxicology SC Toxicology GA 155KC UT WOS:000319745600009 PM 23278212 ER PT J AU Venkataramani, AS Maughan-Brown, B AF Venkataramani, Atheendar S. Maughan-Brown, Brendan TI Effects of Household Shocks and Poverty on the Timing of Traditional Male Circumcision and HIV Risk in South Africa SO AIDS AND BEHAVIOR LA English DT Article DE Economic shocks; Poverty; Male circumcision; HIV; South Africa ID SEXUAL-BEHAVIOR; INFECTION; PREVENTION; HEALTH; ACCEPTABILITY; COMPLICATIONS; INTERVENTION; PREVALENCE; WEALTH; MALAWI AB Poverty may influence HIV risk by increasing vulnerability to economic shocks and thereby preventing key health investments. We explored this possibility by examining the relationship between household shocks and the timing of traditional male circumcision, a practice associated with considerable expense and whose HIV-prevention benefits are larger when done earlier, even within young adulthood. Using unique data on a sample of Xhosa men, a group that almost universally practices traditional circumcision, we found that respondents in the poorest households delayed circumcision by 2 years if a household member experienced loss of income or death and/or illness. The impact of these shocks declined with increasing household income. Our findings suggest that interventions that work to mitigate the impact of shocks among the poor may be useful in HIV prevention efforts. More generally, they illustrate that the relationship between HIV and wealth may be more nuanced than assumed in previous work. C1 [Venkataramani, Atheendar S.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02138 USA. [Maughan-Brown, Brendan] Univ Cape Town, SALDRU, ZA-7701 Cape Town, South Africa. RP Maughan-Brown, B (reprint author), Univ Cape Town, SALDRU, ZA-7701 Cape Town, South Africa. EM brendan.maughanbrown@gmail.com NR 27 TC 0 Z9 0 U1 1 U2 11 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 JUN PY 2013 VL 17 IS 5 BP 1668 EP 1674 DI 10.1007/s10461-013-0459-3 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 150SZ UT WOS:000319412800009 PM 23536141 ER PT J AU Vogenthaler, NS Kushel, MB Hadley, C Frongillo, EA Riley, ED Bangsberg, DR Weiser, SD AF Vogenthaler, Nicholas S. Kushel, Margot B. Hadley, Craig Frongillo, Ed A., Jr. Riley, Elise D. Bangsberg, David R. Weiser, Sheri D. TI Food Insecurity and Risky Sexual Behaviors Among Homeless and Marginally Housed HIV-Infected Individuals in San Francisco SO AIDS AND BEHAVIOR LA English DT Article DE Food insecurity; HIV/AIDS; Sexual risk ID INJECTION-DRUG USERS; INSUFFICIENCY; HIV/AIDS; ATLANTA; HAART; VULNERABILITY; PREVALENCE; SYMPTOMS; POVERTY; AFRICA AB Food insecurity is common among HIV-infected populations in resource-rich and resource-poor countries. We hypothesized that food insecurity would be associated with risky sexual behaviors. We examined this hypothesis among all sexually active participants (n = 154) in the Research on Access to Care in the Homeless (REACH) cohort in San Francisco. The outcomes were unprotected vaginal or anal sex and multiple sexual partners during the prior 90 days. Associations were examined using repeated measures multivariable logistic regression analyses. Food insecurity was independently associated with unprotected sexual activity (AOR = 2.01 for each five point increase in HFIAS scale, 95 % CI 1.31-3.10) and multiple sexual partners (AOR = 1.54 for each five-point increase in HFIAS scale, 95 % CI 1.05-2.29). Food insecurity is a risk factor for unprotected sexual activity and multiple sexual partners among homeless and marginally housed HIV-infected individuals in San Francisco. Measures to alleviate food insecurity may play a role in decreasing secondary HIV transmission. C1 [Vogenthaler, Nicholas S.] Hennepin Cty Med Ctr, Div Infect Dis, Minneapolis, MN 55415 USA. [Kushel, Margot B.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Hadley, Craig] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. [Frongillo, Ed A., Jr.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Riley, Elise D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. RP Vogenthaler, NS (reprint author), Hennepin Cty Med Ctr, Div Infect Dis, 701 Pk Ave,O1, Minneapolis, MN 55415 USA. EM nicholas.vogenthaler@hcmed.org RI Nguyen, Giang/D-9027-2016 FU NCRR NIH HHS [UL1 RR024131]; NIAID NIH HHS [P30 AI060354]; NIMH NIH HHS [K-24 MH 87227, K23 MH079713, K23 MH079713-01, K24 MH087227, R01 MH054907]; PHS HHS [R0-1 54907] NR 35 TC 12 Z9 13 U1 0 U2 11 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 JUN PY 2013 VL 17 IS 5 BP 1688 EP 1693 DI 10.1007/s10461-012-0355-2 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 150SZ UT WOS:000319412800012 PM 23086429 ER PT J AU O'Cleirigh, C Newcomb, ME Mayer, KH Skeer, M Traeger, L Safren, SA AF O'Cleirigh, Conall Newcomb, Michael E. Mayer, Kenneth H. Skeer, Margie Traeger, Lara Safren, Steven A. TI Moderate Levels of Depression Predict Sexual Transmission Risk in HIV-Infected MSM: A Longitudinal Analysis of Data From Six Sites Involved in a "Prevention for Positives" Study SO AIDS AND BEHAVIOR LA English DT Article DE HIV prevention with positives; Men who have sex with men; Sexual risk; Depression ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONTROLLED-TRIAL; YOUNG MEN; WOMEN; THERAPY; SCALE AB Depression is highly comorbid with HIV and may contribute to increased sexual transmission risk behavior (TRB) amongst HIV-infected MSM, the largest risk group for HIV in the U.S. However, examinations of this effect are inconsistent. The present longitudinal analyses of 746 HIV-infected MSM is from a multi-site "prevention for positives" study. A non-linear association between depression and TRB emerged. Moderate levels of depression (compared to either low or high levels) were associated with a more modest decline in the odds of sexual risk behavior over 12-month follow-up. Assessing depression in HIV primary care settings may help to identify those at risk and integrating the treatment of depression into secondary prevention and treatment initiatives may decrease the likelihood of sexual risk and help to contain the epidemic among MSM. C1 [O'Cleirigh, Conall; Newcomb, Michael E.; Traeger, Lara; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [O'Cleirigh, Conall; Newcomb, Michael E.; Mayer, Kenneth H.; Traeger, Lara; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [O'Cleirigh, Conall; Newcomb, Michael E.; Mayer, Kenneth H.; Skeer, Margie; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Hosp, Boston, MA USA. RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cocleirigh@partners.org FU NIDA NIH HHS [R34 DA031038]; NIMH NIH HHS [R01 MH095624, K24 MH094214, K24MH094214]; PHS HHS [H97HA01293-01-00] NR 24 TC 24 Z9 24 U1 1 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 JUN PY 2013 VL 17 IS 5 BP 1764 EP 1769 DI 10.1007/s10461-013-0462-8 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 150SZ UT WOS:000319412800020 PM 23605154 ER PT J AU Simon, HB AF Simon, Harvey B. TI The Write Stuff: How Good Writing Can Enhance Patient Care and Professional Growth SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID SHARED DECISION-MAKING; HEALTH LITERACY; COHORT; RECORD C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. [Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, HB (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 13 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2013 VL 126 IS 6 BP 467 EP 471 DI 10.1016/j.amjmed.2012.11.020 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 146TY UT WOS:000319116400018 PM 23561628 ER PT J AU Clair, C Meigs, JB Rigotti, NA AF Clair, Carole Meigs, James B. Rigotti, Nancy A. TI Smoking Behavior among US Adults with Diabetes or Impaired Fasting Glucose SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Diabetes; Impaired fasting glucose; Smoking ID CIGARETTE-SMOKING; NATIONAL-HEALTH; BODY-FAT; RISK; INDIVIDUALS; POPULATION; DISEASE; TRENDS AB BACKGROUND: Cigarette smoking is a well-known cardiovascular risk factor and its impact on cardiovascular disease is even greater among people with diabetes. The aim of this study is to compare the prevalence and determinants of smoking among US adults with diabetes or impaired fasting glucose, and those without diabetes or impaired fasting glucose. METHODS: Weanalyzed data from the National Health and Nutrition Examination Surveys (1999-2008). Age-adjusted prevalence of smoking was calculated, and we used logistic regression models to identify the correlates of smoking among people with diabetes, impaired fasting glucose, and normal glucose metabolism. RESULTS: Among 24,649 participants >= 20 years old, age-adjusted smoking prevalence was 25.7% in 3111 individuals with diabetes, 24.2% in 3557 individuals with impaired fasting glucose, and 24.1% in 17,981 individuals without diabetes. Smoking prevalence did not differ across groups or change over time (1999-2008) in any group. Younger age, less education, more alcohol consumption, less physical activity, and major depression symptoms were associated with smoking in people with diabetes, impaired fasting glucose, and normal glucose metabolism. CONCLUSIONS: In the US, smoking prevalence among people with diabetes and impaired fasting glucose has not changed and is comparable with the nondiabetic population. Tobacco control efforts should be intensified among this population at high risk for complications and mortality. (C) 2013 Elsevier Inc. All rights reserved. C1 [Clair, Carole; Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. RP Clair, C (reprint author), Dept Ambulatory Care & Community Med, 44 Bugnon Ave, CH-1011 Lausanne, Switzerland. EM carole.willi@gmail.com RI Clair, Carole/D-9786-2014 OI Clair, Carole/0000-0001-5281-0943 FU Swiss National Science Foundation [PBLAP3-127728/1]; SICPA foundation; National Heart Lung and Blood Institute [K24-HL04440]; National Institute of Diabetes and Digestive Kidney Disease [K24 DK080140]; Pfizer; Nabi Biopharmaceuticals FX CC was supported by a grant from the Swiss National Science Foundation, PBLAP3-127728/1, and by a grant from the SICPA foundation. NAR's effort was supported by a grant from the National Heart Lung and Blood Institute (K24-HL04440). JBM was supported by National Institute of Diabetes and Digestive Kidney Disease grant K24 DK080140.; Conflict of Interest: CC does not report any conflict of interest. NAR has consulted without pay for Pfizer and Free and Clear, Inc. about smoking cessation and has conducted research projects sponsored by Pfizer and Nabi Biopharmaceuticals. JBM does not report any conflicts of interest. NR 14 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2013 VL 126 IS 6 BP 541 EP U117 DI 10.1016/j.amjmed.2012.11.029 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 146TY UT WOS:000319116400031 ER PT J AU Willett, LL Estrada, CA Adams, M Arora, V Call, S Chacko, K Chaudhry, S Halvorsen, AJ Hopkins, R McDonald, FS AF Willett, Lisa L. Estrada, Carlos A. Adams, Michael Arora, Vineet Call, Stephanie Chacko, Karen Chaudhry, Saima Halvorsen, Andrew J. Hopkins, Robert McDonald, Furman S. TI Challenges with Continuity Clinic and Core Faculty Accreditation Requirements SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID INTERNAL-MEDICINE; PROGRAM-DIRECTORS; EDUCATION C1 [Willett, Lisa L.] Univ Alabama Birmingham, Dept Med, Div Gen Internal Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA. [Adams, Michael] Medstar Georgetown Univ Hosp, Washington, DC USA. [Arora, Vineet] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Call, Stephanie] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA. [Chacko, Karen] Univ Colorado, Primary Care Internal Med Residency Program, Denver, CO 80202 USA. [Chacko, Karen] Univ Colorado, Internal Med Residency Program, Denver, CO 80202 USA. [Chaudhry, Saima] Hofstra North Shore LIJ Sch Med, Dept Med, Internal Med Residency Program, Hempstead, NY USA. [Halvorsen, Andrew J.] Mayo Clin, Dept Med, Internal Med Residency Off Educ Innovat, Rochester, MI USA. [Hopkins, Robert] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Hopkins, Robert] Univ Arkansas Med Sci, Div Gen Internal Med, Little Rock, AR 72205 USA. [McDonald, Furman S.] Mayo Clin, Dept Med, Rochester, MI USA. [McDonald, Furman S.] Mayo Clin, Div Gen, Rochester, MI USA. [McDonald, Furman S.] Mayo Clin, Hosp Internal Med, Rochester, MI USA. RP Willett, LL (reprint author), Univ Alabama Birmingham, Dept Med, Div Gen Internal Med, BDB 341,1720 2nd Ave S, Birmingham, AL 35294 USA. EM lwillett@uab.edu OI Arora, Vineet/0000-0002-4745-7599 NR 16 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2013 VL 126 IS 6 BP 550 EP 556 DI 10.1016/j.amjmed.2013.02.008 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 146TY UT WOS:000319116400033 PM 23684398 ER PT J AU Wasserman, MS Rose, AJ AF Wasserman, Michael S. Rose, Adam J. TI An Unusual Presenting Complaint for Herpes Zoster SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Wasserman, Michael S.; Rose, Adam J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Wasserman, Michael S.; Rose, Adam J.] VA Boston Healthcare Syst, Boston, MA USA. [Rose, Adam J.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Wasserman, MS (reprint author), 72 East Concord St,A-208, Boston, MA 02118 USA. EM michaelswasserman@gmail.com NR 2 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2013 VL 126 IS 6 BP E3 EP E4 DI 10.1016/j.amjmed.2013.01.015 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 146TY UT WOS:000319116400002 PM 23541377 ER PT J AU Kerr, DA Lopez, HU Deshpande, V Hornicek, FJ Duan, ZF Zhang, YX Rosenberg, AE Borger, DR Nielsen, GP AF Kerr, Darcy A. Lopez, Hector U. Deshpande, Vikram Hornicek, Francis J. Duan, Zhenfeng Zhang, Yaxia Rosenberg, Andrew E. Borger, Darrel R. Nielsen, G. Petur TI Molecular Distinction of Chondrosarcoma From Chondroblastic Osteosarcoma Through IDH1/2 Mutations SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE IDH1; IDH2; chondrosarcoma; dedifferentiation; osteosarcoma ID ISOCITRATE DEHYDROGENASE 1; IDH2 MUTATIONS; MYELOPROLIFERATIVE NEOPLASMS; MAFFUCCI SYNDROME; OLLIER DISEASE; CANCER; TUMORS; 2-HYDROXYGLUTARATE; DIFFERENTIATION; LEUKEMIA AB Distinguishing chondrosarcoma from chondroblastic osteosarcoma can be difficult and highly subjective, especially on a small biopsy specimen. This distinction is critical in determining the most accurate prognosis and appropriate treatment modality, as adjuvant chemotherapy with surgery is standard treatment for osteosarcoma, whereas chondrosarcoma is generally treated by surgical excision alone. Cartilaginous neoplasms have recently been shown to frequently (56%) harbor gene mutations in the metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and IDH2 (IDH1 > IDH2), whereas other mesenchymal tumors lack these genetic aberrations. We investigated whether the presence of IDH1/2 mutations can be used to distinguish chondrosarcoma from chondroblastic osteosarcoma. Tumors including 25 predominantly high-grade chondrosarcomas and 65 osteosarcomas (44 chondroblastic osteosarcomas and 21 mixed osteosarcomas with a chondroblastic component) were evaluated, and a total of 59 cases (66%) were suitable for genotyping. Mutational analysis was performed using a multiplexed polymerase chain reaction genotyping platform to query for hotspot mutations in the genes IDH1 at codon R132. IDH1-negative cases underwent Sanger sequencing of IDH2 exon 4. No osteosarcomas (0/36) and 61% of chondrosarcomas (14/23) harbored a somatic mutation in IDH1/2, with the majority (86%) of mutations found in the IDH1 gene. IDH1/2 mutation analysis appears to be a promising biomarker for the distinction of chondrosarcoma from chondroblastic osteosarcoma. A positive result strongly favors the diagnosis of chondrosarcoma over chondroblastic osteosarcoma. The presence of IDH1/2 mutations can also help confirm the diagnosis of dedifferentiated chondrosarcoma when the tumor displays osteosarcomatous differentiation. C1 [Kerr, Darcy A.; Deshpande, Vikram; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lopez, Hector U.; Borger, Darrel R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Kerr, Darcy A.; Deshpande, Vikram; Hornicek, Francis J.; Duan, Zhenfeng; Borger, Darrel R.; Nielsen, G. Petur] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Yaxia; Rosenberg, Andrew E.] Univ Miami, Dept Pathol, Miami, FL USA. [Zhang, Yaxia; Rosenberg, Andrew E.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, MGH Pathol Serv, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM gnielsen@partners.org FU Vickery Grant, MGH Pathology Department FX Supported by a Vickery Grant, MGH Pathology Department. D.R.B. is a paid consultant for Bio-Reference Laboratories Inc. (licensee of SNaPshot). For the remaining authors none were declared. NR 28 TC 21 Z9 21 U1 0 U2 7 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 JUN PY 2013 VL 37 IS 6 BP 787 EP 795 DI 10.1097/PAS.0b013e31827ab703 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 145WE UT WOS:000319049000001 PM 23598960 ER PT J AU Gilks, CB Oliva, E Soslow, RA AF Gilks, C. Blake Oliva, Esther Soslow, Robert A. TI Poor Interobserver Reproducibility in the Diagnosis of High-grade Endometrial Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial carcinoma; subtype diagnosis; reproducibility; serous; endometrioid ID GYNECOLOGIC-ONCOLOGY-GROUP; CLEAR-CELL; CLINICOPATHOLOGICAL ANALYSIS; SEROUS CARCINOMAS; OVARIAN-CARCINOMA; BREAST-CANCER; TRIAL; DIFFERENTIATION; RADIOTHERAPY; MULTICENTER AB Patients with high-grade subtypes of endometrial carcinoma (grade 3 endometrioid, serous, clear cell, or carcinosarcoma) have a relatively poor prognosis. The specific subtype may be used to guide patient management, but there is little information on the reproducibility of subtype diagnosis in cases of high-grade endometrial carcinoma. Fifty-six cases diagnosed as a high-grade subtype of endometrial carcinoma were identified from the pathology archives of Vancouver General Hospital. All slides for each case were reviewed independently by 3 pathologists, who diagnosed the specific tumor subtype(s) and assigned the percentage of each subtype for mixed tumors. Agreement between observers was categorized as follows: major disagreement: (A) no consensus for low-grade endometrioid versus high- grade carcinoma (any subtype), or (B) no consensus with respect to the predominant high- grade subtype present; minor disagreement: consensus was reached about the cell type of the predominant component of a mixed tumor, but there was disagreement about the subtype of the minor component. A tissue microarray was constructed from these cases and immunostained for p16, ER, PR, PTEN, and p53. In 35 of 56 (62.5%) cases, there was agreement between all 3 reviewers regarding the subtype diagnosis of the exclusive (in pure tumors) or predominant (in mixed tumors) high- grade component. Of these cases, there was a minor disagreement (ie, disagreement about the minor high- grade component subtype in a mixed tumor) in 4 cases (4/56, 7.1%). In 20 of 56 (35.8%) cases there was a major disagreement; in 17 (30.4%) of these cases there was no consensus about the major subtype diagnosis, whereas in 3 (5.4%) cases there was disagreement about whether a component of high- grade endometrial carcinoma was present. In the final case, all 3 reviewers diagnosed the case as low-grade endometrioid carcinoma, disagreeing with the original diagnosis of high- grade carcinoma. The most frequent areas of disagreement were serous versus clear cell (7 cases) and serous versus grade 3 endometrioid (6 cases). Immunostaining results using the 5-marker immunopanel were then used to adjudicate in the 6 cases in which there was disagreement between reviewers with respect to serous versus endometrioid carcinoma, and these supported a diagnosis of serous carcinoma in 4 of 6 cases and endometrioid carcinoma in 2 of 6 cases. Pairwise comparison between the reviewers for the 20 cases classified as showing major disagreement was as follows: reviewer 1 and reviewer 2 agreed in 5/20 cases, reviewer 1 and reviewer 3 agreed in 7/20 cases, and reviewer 2 and reviewer 3 agreed in 8/20 cases, indicating that disagreements were not because of a single reviewer holding outlier opinions. Diagnostic consensus among 3 reviewers about the exclusive or major subtype of high- grade endometrial carcinoma was reached in only 35/56 (62.5%) cases, and in 4 of these cases there was disagreement about the minor component present. This poor reproducibility did not reflect systematic bias on the part of any 1 reviewer. There is a need for molecular tools to aid in the accurate and reproducible diagnosis of high- grade endometrial carcinoma subtype. C1 [Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Gilks, C. Blake] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Gilks, CB (reprint author), Vancouver Gen Hosp, Dept Pathol & Lab Med, Rm 1503,1st Floor JPPN,855 West 12th Ave, Vancouver, BC V5Z 1M9, Canada. EM blake.gilks@vch.ca OI Soslow, Robert/0000-0002-7269-5898 NR 34 TC 53 Z9 53 U1 2 U2 7 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 JUN PY 2013 VL 37 IS 6 BP 874 EP 881 DI 10.1097/PAS.0b013e31827f576a PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 145WE UT WOS:000319049000011 PM 23629444 ER PT J AU Shanmugasundararaj, S Zhou, XJ Neunzig, J Bernhardt, R Cotten, JF Ge, R Miller, KW Raines, DE AF Shanmugasundararaj, Sivananthaperumal Zhou, Xiaojuan Neunzig, Jens Bernhardt, Rita Cotten, Joseph F. Ge, Rile Miller, Keith W. Raines, Douglas E. TI . Carboetomidate: An Analog of Etomidate That Interacts Weakly with 11 beta-Hydroxylase SO ANESTHESIA AND ANALGESIA LA English DT Article ID ADRENOCORTICAL-FUNCTION; CYTOCHROME P4502B4; ANESTHETIC ETOMIDATE; ANGSTROM RESOLUTION; BINDING; COORDINATION; INHIBITION; IMIDAZOLE; INSIGHT AB BACKGROUND: Carboetomidate is a pyrrole etomidate analog that is 3 orders of magnitude less potent an inhibitor of in vitro cortisol synthesis than etomidate (an imidazole) and does not inhibit in vivo steroid production. Although carboetomidate's reduced functional effect on steroid synthesis is thought to reflect lower binding affinity to 11 beta-hydroxylase, differential binding to this enzyme has never been experimentally demonstrated. In the current study, we tested the hypothesis that carboetomidate and etomidate bind with differential affinity to 11 beta-hydroxylase by comparing their abilities to inhibit photoaffinity labeling of purified enzyme by a photoactivatable etomidate analog and to modify the enzyme's absorption spectrum in a way that is indicative of ligand binding. In addition, we made a preliminary exploration of the manner in which etomidate and carboetomidate might differentially interact with this site using spectroscopic methods as well as molecular modeling techniques to better understand the structural basis for their selectivity. METHODS: The ability of azi-etomidate to inhibit cortisol synthesis was tested by assessing its ability to inhibit cortisol synthesis by H295R cells. The binding affinities of etomidate and carboetomidate to 11 beta-hydroxylase were compared by assessing their abilities to (1) inhibit photoincorporation of the photolabile etomidate analog [H-3]azi-etomidate into the enzyme and (2) modify the absorption spectrum of the enzyme's heme group. In silico docking studies of etomidate, carboetomidate, and azi-etomidate binding to 11 beta-hydroxylase were performed using the computer software GOLD. RESULTS: Similar to etomidate, azi-etomidate potently inhibits in vitro cortisol synthesis. Etomidate inhibited [H-3]azi-etomidate photolabeling of 11 beta-hydroxylase in a concentration-dependent manner. At a concentration of 40 mu M, etomidate reduced photoincorporation of [H-3] azi-etomidate by 96% +/- 1% whereas carboetomidate had no experimentally detectable effect. On addition of etomidate to 11 beta-hydroxylase, a type 2 difference spectrum was produced indicative of etomidate complexation with the enzyme's heme iron; carboetomidate had no effect whereas azi-etomidate produced a reverse type 1 spectrum. Computer modeling studies predicted that etomidate, carboetomidate, and azi-etomidate can fit into the heme-containing pocket that forms 11 beta-hydroxylase's active site and pose with their carbonyl oxygens interacting with the heme iron and their phenyl rings stacking with phenylalanine-80. However, additional unique poses were identified for etomidate and azi-etomidate that likely account for their higher affinities. CONCLUSIONS: Carboetomidate's reduced ability to suppress in vitro and in vivo steroid synthesis as compared with etomidate reflects its lower binding affinity to 11 beta-hydroxylase and may be attributed to carboetomidate's inability to form a coordination bond with the heme iron located at the enzyme's active site. C1 [Shanmugasundararaj, Sivananthaperumal; Zhou, Xiaojuan; Cotten, Joseph F.; Ge, Rile; Miller, Keith W.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Neunzig, Jens; Bernhardt, Rita] Univ Saarland, Inst Biochem, Saarbrucken, Germany. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health, Bethesda, MD [R01-GM087316, R21-DA029253]; Deutsche Forschungsgemeinschaft [FOR 13698]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; National Institutes of Health [P41 RR-01081]; [K08-GM083216] FX This research was supported by grants to D.E.R. (R01-GM087316 and R21-DA029253 from the National Institutes of Health, Bethesda, MD), R.B. (FOR 13698 from the Deutsche Forschungsgemeinschaft), J.F.C. (K08-GM083216), and by the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital.; The authors thank Prof. Hermans (Department of Pharmacology and Toxicology, Cardiovascular Research Institute, University Maastricht, the Netherlands) for providing them with the published homology model and Wolfgang Reinle for preparation of the protein. Molecular graphics images were produced using the University of California, San Francisco Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by National Institutes of Health P41 RR-01081). NR 26 TC 3 Z9 4 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2013 VL 116 IS 6 BP 1249 EP 1256 DI 10.1213/ANE.0b013e31828b3637 PG 8 WC Anesthesiology SC Anesthesiology GA 154XU UT WOS:000319710800011 PM 23492967 ER PT J AU Bateman, BT Mhyre, JM Ehrenfeld, J Kheterpal, S Abbey, KR Argalious, M Berman, MF St Jacques, P Levy, W Loeb, RG Paganelli, W Smith, KW Wethington, KL Wax, D Pace, NL Tremper, K Sandberg, WS AF Bateman, Brian T. Mhyre, Jill M. Ehrenfeld, Jesse Kheterpal, Sachin Abbey, Kenneth R. Argalious, Maged Berman, Mitchell F. St Jacques, Paul Levy, Warren Loeb, Robert G. Paganelli, William Smith, Kelly W. Wethington, Kevin L. Wax, David Pace, Nathan L. Tremper, Kevin Sandberg, Warren S. TI The Risk and Outcomes of Epidural Hematomas After Perioperative and Obstetric Epidural Catheterization: A Report from the Multicenter Perioperative Outcomes Group Research Consortium SO ANESTHESIA AND ANALGESIA LA English DT Article ID REGIONAL-ANESTHESIA; COMPLICATIONS; THERAPY AB BACKGROUND: In this study, we sought to determine the frequency and outcomes of epidural hematomas after epidural catheterization. METHODS: Eleven centers participating in the Multicenter Perioperative Outcomes Group used electronic anesthesia information systems and quality assurance databases to identify patients who had epidural catheters inserted for either obstetrical or surgical indications. From this cohort, patients undergoing laminectomy for the evacuation of hematoma within 6 weeks of epidural placement were identified. RESULTS: Seven of 62,450 patients undergoing perioperative epidural catheterizations developed hematoma requiring surgical evacuation. The event rate was 11.2 x 10(-5)(95% confidence interval [CI], 4.5 x 10(-5) to 23.1 x 10(-5)). Four of the 7 had anticoagulation/antiplatelet therapy that deviated from American Society of Regional Anesthesia guidelines. None of 79,837 obstetric patients with epidural catheterizations developed hematoma (upper limit of the 95% CI, 4.6 x 10(-5)). The hematoma rate in obstetric epidural catheterizations was significantly lower than in perioperative epidural catheterizations (P = 0.003). CONCLUSIONS: In this series, the 95% CI for the frequency of epidural hematoma requiring laminectomy after epidural catheter placement for perioperative anesthesia/analgesia was 1 event per 22,189 placements to 1 event per 4330 placements. Risk was significantly lower in obstetric epidurals. C1 [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bateman, Brian T.] Harvard Univ, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Mhyre, Jill M.; Kheterpal, Sachin; Tremper, Kevin] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA. [Ehrenfeld, Jesse] Vanderbilt Univ, Dept Anesthesiol & Biomed Informat, Nashville, TN USA. [Abbey, Kenneth R.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Argalious, Maged] Cleveland Clin, Cleveland, OH 44106 USA. [Berman, Mitchell F.] Columbia Univ, Dept Anesthesiol, New York, NY USA. [St Jacques, Paul; Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [St Jacques, Paul; Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [St Jacques, Paul; Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37212 USA. [Levy, Warren] Univ Penn, Dept Anesthesia, Perelman Sch Med, Philadelphia, PA 19104 USA. [Loeb, Robert G.] Univ Arizona, Dept Anesthesiol, Tucson, AZ USA. [Paganelli, William] Univ Vermont, Fletcher Allen Hlth Care, Burlington, VT USA. [Smith, Kelly W.; Wethington, Kevin L.; Pace, Nathan L.] Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA. [Argalious, Maged] Mt Sinai Sch Med, Dept Anesthesiol, New York, NY USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM BBateman@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140 NR 10 TC 35 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2013 VL 116 IS 6 BP 1380 EP 1385 DI 10.1213/ANE.0b013e318251daed PG 6 WC Anesthesiology SC Anesthesiology GA 154XU UT WOS:000319710800029 PM 22504213 ER PT J AU Crane, C Cornejo, A Lyons, R Alter, GJ AF Crane, Curtis Cornejo, Agustin Lyons, Robert Alter, Gary J. TI Urethral Reconstruction Using a Prefabricated Pedicled Gracilis Flap SO ANNALS OF PLASTIC SURGERY LA English DT Article DE urethral injury; urethral disruption; urethral reconstruction; pedicled gracilis flap; Fournier reconstruction AB This case study describes a patient who experienced an iatrogenic urethral injury because of a Fournier gangrene debridement. Because of the extent of the debridement, which resected all penile and scrotal dartos tissue, no local flaps that would typically be used to reconstruct a urethral disruption were possible. The authors chose to use a prefabricated pedicled gracilis flap to restore urethral continuity. C1 [Crane, Curtis; Alter, Gary J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Plast Surg, San Antonio, TX 78229 USA. [Cornejo, Agustin] Univ Texas Hlth Sci Ctr San Antonio, Dept Gen Surg, San Antonio, TX 78229 USA. [Lyons, Robert] South Texas Vet Hlth Care Syst, Audie L Murphy Surg Serv, San Antonio, TX USA. [Alter, Gary J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Crane, C (reprint author), Dept Plast Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cnd51924@yahoo.com NR 5 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 2013 VL 70 IS 6 BP 691 EP 693 DI 10.1097/SAP.0b013e3182414843 PG 3 WC Surgery SC Surgery GA 146DA UT WOS:000319068200020 PM 22791063 ER PT J AU Zhao, GF Yu, YM Kaneki, M Tompkins, RG Fischman, AJ AF Zhao, Gaofeng Yu, Yong-Ming Kaneki, Masao Tompkins, Ronald G. Fischman, Alan J. TI Simvastatin Protects Hepatocytes From Apoptosis by Suppressing the TNF-alpha/Caspase-3 Signaling Pathway in Mice With Burn Injury SO ANNALS OF SURGERY LA English DT Article DE Apoptosis; Caspase-3; Hepatocyte; Simvastatin; tumor necrosis factor alpha ID INDUCED OXIDATIVE INJURY; INDUCED LIVER-INJURY; THERMAL-INJURY; REMOTE ORGANS; STRESS; CANCER; TNF; ROSUVASTATIN; INFECTION; RATS AB Objective: To investigate the liver cellular apoptosis in response to burn injury and find out if statin treatment can ameliorate this process. The hypothesis is that statin may modulate apoptosis-related gene expression and thereby reduce hepatocytic apoptosis after burn injury. Methods: Mice were subjected to 30% full-thickness burn injury and then treated either with or without simvastatin. The livers were harvested for histological assessment and determinations of gene expression. To investigate the mechanism involved, tumor necrosis factor (TNF)-alpha and caspase-3 knockout (KO) mice were also used to evaluate the effects of burn injury and simvastatin treatment on burn-induced liver injury. The effects of simvastatin on TNF-alpha and caspase-3 expressions were also evaluated in cultured mouse hepatocytes. Results: Burn injury induced significant liver damage, which was indicated by striking levels of apoptosis. Simvastatin reduced the apoptotic index in the livers of mice with burn injury and this effect could be abrogated by TNF-alpha or caspase-3 inhibitors. Simvastatin also decreased burn-induced TNF-alpha and caspase-3 expression in the liver. TNF-alpha and caspase-3 KO mice demonstrated lower levels of apoptotic hepatocytes in response to burn, and simvastatin did not further decrease hepatocyte apoptosis in either strain of KO mice. An in vitro study demonstrated that simvastatin suppresses TNF-alpha and caspase-3 expression in primary cultures of mouse hepatocytes. Conclusions: Simvastatin reduces mouse hepatocyte apoptosis by suppressing expression of the TNF-alpha/caspase-3 pathway. C1 [Zhao, Gaofeng] Massachusetts Gen Hosp, Shriners Hosp Children, Surg Serv, Boston, MA 02114 USA. [Zhao, Gaofeng] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhao, GF (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Surg Serv, 55 Fruit St, Boston, MA 02114 USA. EM jingxizh@yahoo.com FU Shriners Hospitals for Children [87100]; National Institutes of Health [P50 21700] FX This study was supported in part by grants from Shriners Hospitals for Children (Shriners grant 87100) and the National Institutes of Health (P50 21700). The authors declare no conflicts of interest. NR 27 TC 1 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 2013 VL 257 IS 6 BP 1129 EP 1136 DI 10.1097/SLA.0b013e318273fdca PG 8 WC Surgery SC Surgery GA 145VP UT WOS:000319047300031 PM 23275311 ER PT J AU Joehanes, R Ying, SX Huan, TX Johnson, AD Raghavachari, N Wang, R Liu, PC Woodhouse, KA Sen, SK Tanriverdi, K Courchesne, P Freedman, JE O'Donnell, CJ Levy, D Munson, PJ AF Joehanes, Roby Ying, Saixia Huan, Tianxiao Johnson, Andrew D. Raghavachari, Nalini Wang, Richard Liu, Poching Woodhouse, Kimberly A. Sen, Shurjo K. Tanriverdi, Kahraman Courchesne, Paul Freedman, Jane E. O'Donnell, Christopher J. Levy, Daniel Munson, Peter J. TI Gene Expression Signatures of Coronary Heart Disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE biomarkers; coronary artery disease; coronary heart disease; gene expression; myocardial infarction; transcriptomics ID GENOME-WIDE ASSOCIATION; UBIQUITIN-PROTEASOME SYSTEM; BLOOD MONONUCLEAR-CELLS; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; GRANZYME-B; NONDIABETIC PATIENTS; WHOLE-BLOOD; APOPTOSIS; PROTEIN AB Objective-To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and 188 age-and sex-matched controls who were participants in the Framingham Heart Study. Approach and Results-A total of 35 genes were differentially expressed in cases with CHD versus controls at false discovery rate< 0.5, including GZMB, TMEM56, and GUK1. Cluster analysis revealed 3 gene clusters associated with CHD, 2 linked to increased erythrocyte production and a third to reduced natural killer and T cell activity in cases with CHD. Exon-level results corroborated and extended the gene-level results. Alternative splicing analysis suggested that GUK1 and 38 other genes were differentially spliced in cases with CHD versus controls. Gene Ontology analysis linked ubiquitination and T-cell-related pathways with CHD. Conclusions-Two bioinformatically defined groups of genes show consistent associations with CHD. Our findings are consistent with the hypotheses that hematopoesis is upregulated in CHD, possibly reflecting a compensatory mechanism, and that innate immune activity is disrupted in CHD or altered by its treatment. Transcriptomic signatures may be useful in identifying pathways associated with CHD and point toward novel therapeutic targets for its treatment and prevention. C1 [Joehanes, Roby; Huan, Tianxiao; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI Framingham Heart Study, Framingham, MA USA. [Joehanes, Roby; Huan, Tianxiao; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Joehanes, Roby; Ying, Saixia; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Raghavachari, Nalini; Wang, Richard; Liu, Poching; Woodhouse, Kimberly A.] NHLBI, DNA Sequencing & Genom Core, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Sen, Shurjo K.] NHGRI, NIH, Bethesda, MD 20892 USA. [Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Sch Med, High Throughput Gene Express Biomarker Core, Worcester, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Munson, PJ (reprint author), Ctr Informat Technol, Math & Stat Comp Lab, NIH Bldg 12A,Room 2039, Bethesda, MD 20892 USA. EM Levyd@NIH.Gov; Munson@helix.nih.gov RI Huan, Tianxiao/D-6020-2014; Johnson, Andrew/G-6520-2013 FU Center for Population Studies; Boston University School of Medicine; National Heart, Lung, and Blood Institute [N01-HC-25195]; Intramural Research Programs of the National Heart, Lung, and Blood Institute, the Center for Information Technology of the National Institutes of Health FX This work was supported by funds from the Center for Population Studies and the Intramural Research Programs of the National Heart, Lung, and Blood Institute, the Center for Information Technology of the National Institutes of Health, and from Boston University School of Medicine. The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute contract N01-HC-25195. NR 47 TC 29 Z9 29 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2013 VL 33 IS 6 BP 1418 EP + DI 10.1161/ATVBAHA.112.301169 PG 37 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 146UR UT WOS:000319119500044 PM 23539218 ER PT J AU van Eijsden, RGE Stassen, C Daenen, L Van Mulders, SE Bapat, PM Siewers, V Goossens, KVY Nielsen, J Delvaux, FR Van Hummelen, P Devreese, B Willaert, RG AF van Eijsden, Rudy G. E. Stassen, Catherine Daenen, Luk Van Mulders, Sebastiaan E. Bapat, Prashant M. Siewers, Verena Goossens, Katty V. Y. Nielsen, Jens Delvaux, Freddy R. Van Hummelen, Paul Devreese, Bart Willaert, Ronnie G. TI A universal fixation method based on quaternary ammonium salts (RNAlater) for omics-technologies: Saccharomyces cerevisiae as a case study SO BIOTECHNOLOGY LETTERS LA English DT Article DE Fluxomics; Genomics; Omics; RNAlater; Saccharomyces cerevisiae; Transcriptomics ID TISSUE STORAGE METHODS; MESSENGER-RNA; PRESERVATION; METABOLISM; NUMBER; FROZEN; YEAST; PCR; DNA AB Genomics, transcriptomics, proteomics and fluxomics are powerful omics-technologies that play a major role in today's research. For each of these techniques good sample quality is crucial. Major factors contributing to the quality of a sample is the actual sampling procedure itself and the way the sample is stored directly after sampling. It has already been described that RNAlater can be used to store tissues and cells in a way that the RNA quality and quantity are preserved. In this paper, we demonstrate that quaternary ammonium salts (RNAlater) are also suitable to preserve and store samples from Saccharomyces cerevisiae for later use with the four major omics-technologies. Moreover, it is shown that RNAlater also preserves the cell morphology and the potential to recover growth, permitting microscopic analysis and yeast cell culturing at a later stage. C1 [van Eijsden, Rudy G. E.] VIB, VIB Nucle Core, Louvain, Belgium. [Stassen, Catherine; Devreese, Bart] Univ Ghent, Dept Biochem & Microbiol, Lab Prot Biochem & Biomol Engn, B-9000 Ghent, Belgium. [Daenen, Luk; Van Mulders, Sebastiaan E.; Delvaux, Freddy R.] Katholieke Univ Leuven, Ctr Malting & Brewing Sci, Dept Microbial & Mol Syst, Louvain, Belgium. [Bapat, Prashant M.] Tech Univ Denmark, Ctr Microbial Biotechnol, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Siewers, Verena; Nielsen, Jens] Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden. [Goossens, Katty V. Y.; Willaert, Ronnie G.] Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Struct Biol, B-1050 Brussels, Belgium. [Van Hummelen, Paul] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Goossens, KVY (reprint author), Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Struct Biol, Pl Laan 2, B-1050 Brussels, Belgium. EM rudy.vaneijsden@vib.be; catherine.stassen@vub.ac.be; prashant.bapat@gmail.com; siewers@chalmers.se; katty.goossens@vub.ac.be; nielsenj@chalmers.se; freddy.delvaux@biw.kuleuven.be; paul_vanhummelen@dfci.harvard.edu; bart.devreese@ugent.be; ronnie.willaert@vub.ac.be RI Devreese, Bart/B-2011-2009; OI Devreese, Bart/0000-0002-9764-2581; Nielsen, Jens/0000-0002-9955-6003 FU Belgian Federal Science Policy Office; Danish Agency for Space and Technology; European Space Agency (ESA) PRODEX program FX The Belgian Federal Science Policy Office, the Danish Agency for Space and Technology, and the European Space Agency (ESA) PRODEX program supported this work. NR 28 TC 4 Z9 5 U1 1 U2 23 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-5492 EI 1573-6776 J9 BIOTECHNOL LETT JI Biotechnol. Lett. PD JUN PY 2013 VL 35 IS 6 BP 891 EP 900 DI 10.1007/s10529-013-1163-0 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 150YK UT WOS:000319427500008 PM 23417260 ER PT J AU Kaplan, JR Kowalczyk, KJ Borza, T Gu, XM Lipsitz, SR Nguyen, PL Friedlander, DF Trinh, QD Hu, JC AF Kaplan, Joshua R. Kowalczyk, Keith J. Borza, Tudor Gu, Xiangmei Lipsitz, Stuart R. Nguyen, Paul L. Friedlander, David F. Quoc-Dien Trinh Hu, Jim C. TI Patterns of care and outcomes of radiotherapy for lymph node positivity after radical prostatectomy SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; radical prostatectomy; radiation therapy; outcomes ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CLINICAL-TRIAL; TERM-FOLLOW-UP; RADIATION-THERAPY; ADJUVANT RADIOTHERAPY; PELVIC LYMPHADENECTOMY; HORMONAL-THERAPY; ANTIGEN LEVEL; CANCER; RISK AB Objective To evaluate the use and outcomes of adjuvant radiation therapy (ART) for men with lymph node (LN)-positive disease after radical prostatectomy (RP) using a population-based approach. Patients and Methods Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 1995 to 2007 was used to identify 577 men with LN metastases discovered during RP and absence of distant metastases, of which 177 underwent ART 1 year of RP. Propensity score models were used to compare overall mortality and prostate cancer-specific mortality (PCSM) for men that did and those that did not receive ART. Results Men in both groups received adjuvant androgen-deprivation therapy at similar rates after propensity weighting adjustments (33.6% vs 33.7%, P=0.977). ART was not associated with differences in overall (5.09 vs 3.77 events per 100 person-years, P=0.153) or PCSM (2.89 vs 1.31, P=0.090) relative to men who did not receive ART. Conclusions ART after RP in men with LN-positive prostate cancer was not associated with improved overall or disease-specific survival, in contrast to previous single-centre studies. Prospective randomised studies are needed to assess the effectiveness of ART in this patient population. C1 [Kaplan, Joshua R.; Borza, Tudor] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA. [Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Gu, Xiangmei; Lipsitz, Stuart R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Friedlander, David F.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. RP Kaplan, JR (reprint author), 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM jrkaplan@partners.org OI Kaplan, Joshua/0000-0001-6153-3829 FU Department of Defense Prostate Cancer Physician Training Award [W81XWH-08-1-0283] FX This work was supported by a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283) presented to Dr Hu. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. NR 34 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2013 VL 111 IS 8 BP 1208 EP 1214 DI 10.1111/bju.12079 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 152GW UT WOS:000319520800020 PM 23551838 ER PT J AU Schiavina, R Borghesi, M Brunocilla, E Manferrari, F Fiorentino, M Vagnoni, V Baccos, A Pultrone, CV Rocca, GC Rizzi, S Martorana, G AF Schiavina, Riccardo Borghesi, Marco Brunocilla, Eugenio Manferrari, Fabio Fiorentino, Michelangelo Vagnoni, Valerio Baccos, Alessandro Pultrone, Cristian Vincenzo Rocca, Giovanni Christian Rizzi, Simona Martorana, Giuseppe TI Differing risk of cancer death among patients with lymph node metastasis after radical prostatectomy and pelvic lymph node dissection: identification of risk categories according to number of positive nodes and Gleason score SO BJU INTERNATIONAL LA English DT Article DE radical prostatectomy; pelvic lymph node dissection; Gleason score; lymph node metastasis; survival ID STAGE D1 T1-3; ANDROGEN DEPRIVATION; EXTRANODAL EXTENSION; DISEASE PROGRESSION; PROGNOSTIC-FACTORS; SURVIVAL; RECURRENCE; IMPACT; THERAPY AB What's known on the subject? and What does the study add? Lymph node (LN) status is one of the most important prognostic variables in patients undergoing radical prostatectomy, but not all patients with node-positive PCa are at the same risk of recurrence and cancer-specific death. In this study we evaluated the role of pathological variables in stratifying the risk of cancer death in patients with prostate cancer. Patients with 1-3 positive LNs and Gleason score (GS) 7 experienced better CSS and OS than those with >3 metastatic LNs and/or GS >7. This evidence could allow urologists to better predict oncological outcomes of patients and select more appropriate therapeutic management. Objectives To evaluate the outcomes in patients with node-positive prostate cancer (PCa) after radical prostatectomy (RP) and pelvic lymph node dissection (PLND) according to the number of positive lymph nodes (LNs). To identify different risk groups among patients with node-positive PCa. Patients and Methods We evaluated 98 consecutive patients with pN1M0 PCa who underwent RP between November 1995 and May 2011. Kaplan-Meier and Cox proportional univariable and multivariable regression models were used to analyse the survival rates. Patients were divided into two groups according to number of positive LNs using the most informative positive LN theshold for predicting survival, then into three different risk groups according to number of positive LNs and pathological Gleason score (GS). Results Mean (range) follow-up was 68.4 (10-192) months. Patients with 1-3 positive LNs (n = 75; 76.5%) had significantly better cancer-specific survival (CSS) and overall survival (OS) compared with those with >3 positive nodes (n = 23; 23.4%; P < 0.01). Patients with 1-3 positive LNs and pathological GS 7 (Group 1) had significantly better CSS than those with >3 positive LNs or GS 8-10 (Group 2 [P = 0.015]). Group 2 patients, moreover, had significantly better CSS (P = 0.019) and OS (P = 0.021) than those with >3 positive LNs and GS 8-10 (Group 3). Conclusions Patients with 1-3 positive LNs have higher CSS and OS rates than those with >3 metastatic LNs. Taking into account the pathological GS, as well as the number of positive nodes, three risk group categories with considerable differences in terms of survival can be found. Patients with LN-positive PCa should be stratified into different groups according to these two measures, to obtain a better prediction of oncological outcomes. C1 [Schiavina, Riccardo; Borghesi, Marco; Brunocilla, Eugenio; Manferrari, Fabio; Vagnoni, Valerio; Baccos, Alessandro; Pultrone, Cristian Vincenzo; Rocca, Giovanni Christian; Rizzi, Simona; Martorana, Giuseppe] Univ Bologna, S Orsola M Malpighi Hosp, Dept Urol, I-40138 Bologna, Italy. [Fiorentino, Michelangelo] Univ Bologna, S Orsola M Malpighi Hosp, Dept Pathol & Mol Oncol, I-40138 Bologna, Italy. [Fiorentino, Michelangelo] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schiavina, R (reprint author), Univ Bologna, S Orsola M Malpighi Hosp, Dept Urol, Palogi 9 St, I-40138 Bologna, Italy. EM rschiavina@yahoo.it OI Borghesi, Marco/0000-0001-6021-6805 NR 31 TC 11 Z9 11 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2013 VL 111 IS 8 BP 1237 EP 1244 DI 10.1111/j.1464-410X.2012.11602.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 152GW UT WOS:000319520800024 PM 23331345 ER PT J AU Bianchi, M Becker, A Hansen, J Trinh, QD Tian, Z Abdollah, F Briganti, A Shariat, SF Perrotte, P Montorsi, F Karakiewicz, PI Sun, M AF Bianchi, Marco Becker, Andreas Hansen, Jens Quoc-Dien Trinh Tian, Zhe Abdollah, Firas Briganti, Alberto Shariat, Shahrokh F. Perrotte, Paul Montorsi, Francesco Karakiewicz, Pierre I. Sun, Maxine TI Conditional survival after nephrectomy for renal cell carcinoma (RCC): changes in future survival probability over time SO BJU INTERNATIONAL LA English DT Article DE renal cell carcinoma; RCC; conditional survival; nephrectomy ID CANCER; DEATH AB Objective To examine the impact of length of survival on future survival probability, otherwise known as the effect of conditional survival (CS), after nephrectomy (NT) in patients diagnosed with renal cell carcinoma (RCC). Patients and Methods Overall, 42090 patients with RCC who underwent NT were abstracted from the Surveillance, Epidemiology, and End Results database (1988-2008). Based on cumulative survival estimates, CS rates were derived according to patient and disease characteristics. Separate multivariable Cox regression analyses were performed for the prediction of cancer-specific mortality (CSM), according to 1-, 2-, 3-, 4- and 5-year survival postoperatively. Results Immediately after surgery, the 5-year cancer-specific survival rate was 83.5%. Amongst patients who survived 1, 2, 3, 4, and 5 years after NT, the probability rates for surviving an additional 5 years were 87.0, 89.6, 90.9, 92.0 and 92.3%, respectively. Provided that patients survived 1 and 2 years after NT, the probability of being CSM-free for another 5 years increased by +4.1 and 4.3% for stage III and +12.9 and 10.3% for stage IV disease, respectively. Similar observations were recorded for patient age, grade, nodal stage and tumour size, and were confirmed upon multivariable analyses. Conclusion Survival probabilities vary according to length of survival after NT. Specifically, even amongst patients with more advanced disease at surgery, a more favourable prognosis can be achieved after surviving for 1-2 years. C1 [Bianchi, Marco; Becker, Andreas; Quoc-Dien Trinh; Tian, Zhe; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada. [Bianchi, Marco; Abdollah, Firas; Briganti, Alberto; Montorsi, Francesco] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy. [Becker, Andreas; Hansen, Jens] Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA. [Shariat, Shahrokh F.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA. [Perrotte, Paul; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 3J4, Canada. RP Becker, A (reprint author), Univ Montreal, Ctr Hlth, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM a.becker@uke.de FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Sante du Qubec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX P. I. K. is partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Qubec, the University of Montreal Department of Surgery and the University of Montreal Health Centre (CHUM) Foundation. All authors made substantial contribution to the preparation of the current manuscript and consented to its final format prior to submission. NR 16 TC 6 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2013 VL 111 IS 8 BP E283 EP E289 DI 10.1111/bju.12115 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 152GW UT WOS:000319520800002 PM 23714646 ER PT J AU Wu, CW Aronson, WJ Terris, MK Presti, JC Kane, CJ Amling, CL Freedland, SJ AF Wu, Chenwei Aronson, William J. Terris, Martha K. Presti, Joseph C., Jr. Kane, Christopher J. Amling, Christopher L. Freedland, Stephen J. TI Diabetes predicts metastasis after radical prostatectomy in obese men: results from the SEARCH database SO BJU INTERNATIONAL LA English DT Article DE diabetes; obesity; race; prostate cancer; metastasis ID CANCER-SPECIFIC MORTALITY; SERUM TESTOSTERONE LEVEL; BODY-MASS INDEX; GROWTH-FACTOR-I; PATHOLOGICAL STAGE; UNITED-STATES; SEX-HORMONES; RISK; MELLITUS; INSULIN AB What's known on the subject? and What does the study add? Diabetes is known to be associated with a slightly lower risk of prostate cancer. Only a limited number of studies have examined the impact of diabetes on prostate cancer outcomes, with mixed results. This study builds on our prior work showing that on the whole, diabetes is not a risk factor for progression to metastases after surgery. However, intriguingly we found a significant interaction with obesity for modifying the relationship between diabetes and progression. If confirmed in future studies, this suggests the mechanisms by which diabetes alters prostate cancer aggressiveness may differ in obese and non-obese men. Objective To examine the association between diabetes and metastasis risk after radical prostatectomy (RP) and to determine if race or obesity modifies this relationship. Patients and Methods Patients comprised 2058 US veterans with prostate cancer (PCa) enrolled in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database and treated with RP between 1988 and 2010. The association of diabetes with metastasis risk or secondary treatment rates was examined using Cox proportional hazards, adjusting for preoperative and, separately, clinical and postoperative findings. The effect modification by race (black vs white) and obesity (body mass index [BMI] 30 vs <30kg/m2) was tested via interaction terms. Results Men with diabetes had higher BMIs and were more likely to be non-white (all P 0.001). On multivariable analysis, diabetes was not associated with metastasis risk (P 0.45), but, among men with diabetes, longer diabetes duration was associated with higher metastasis risk (P 0.035). When stratified by obesity, diabetes was linked with higher metastasis risk in obese but not in non-obese men (P-interaction 0.037), but there was no significant interaction with race (P-interaction 0.56). Diabetes also predicted more aggressive secondary treatment among obese men but less aggressive treatment among non-obese men (hazard ratio 1.39 vs 0.63, P-interaction = 0.006). Where applicable, results were similar for both pre- and postoperative models. Conclusions Diabetes was not associated with metastasis risk overall. Stratification by obesity yielded significant differences, with diabetes linked to a fourfold higher metastasis risk in obese men, despite predicting more aggressive secondary treatment. Longer diabetes duration was also associated with increased metastasis risk. C1 [Wu, Chenwei; Freedland, Stephen J.] Duke Univ, Sch Med, Durham, NC USA. [Wu, Chenwei; Freedland, Stephen J.] Duke Univ, Med Ctr, Durham VA Med Ctr, Urol Sect, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Surg, Div Urol Surg, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC USA. [Aronson, William J.] UCLA Hlth Syst, Dept Urol, Los Angeles, CA USA. [Aronson, William J.] VA Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Sch Med, Dept Urol, Palo Alto, CA USA. [Presti, Joseph C., Jr.] VA Palo Alto Healthcare Syst, Urol Sect, Palo Alto, CA USA. [Kane, Christopher J.] UC San Diego Hlth Syst, Dept Surg, Div Urol, San Diego, CA USA. [Terris, Martha K.] Med Coll Georgia, Dept Surg, Urol Sect, Augusta, GA 30912 USA. [Terris, Martha K.] Charlie Norwood VA Med Ctr, Urol Sect, Augusta, GA USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. RP Freedland, SJ (reprint author), DUMC 2626 Suite 475, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU American Urological Association Foundation/Astellas Rising Star in Urology Award (S.J.F.); Howard Hughes Medical Institute Medical Research Fellows scholarship (C. W.) FX This work was supported by the American Urological Association Foundation/Astellas Rising Star in Urology Award (S.J.F.) and a Howard Hughes Medical Institute Medical Research Fellows scholarship (C.W.) NR 39 TC 7 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2013 VL 111 IS 8 BP E310 EP E318 DI 10.1111/j.1464-410X.2012.11687.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 152GW UT WOS:000319520800006 PM 23305170 ER PT J AU Lin, NU Thomssen, C Cardoso, F Cameron, D Cufer, T Fallowfield, L Francis, PA Kyriakides, S Pagani, O Senkus, E Costa, A Winer, EP AF Lin, Nancy U. Thomssen, Christoph Cardoso, Fatima Cameron, David Cufer, Tanja Fallowfield, Lesley Francis, Prudence A. Kyriakides, Stella Pagani, Olivia Senkus, Elzbieta Costa, Alberto Winer, Eric P. CA ESO-MBC Task Force TI International guidelines for management of metastatic breast cancer (MBC) from the European School of Oncology (ESO)-MBC Task Force: Surveillance, staging, and evaluation of patients with early-stage and metastatic breast cancer SO BREAST LA English DT Review DE Breast cancer; Guidelines; ABC; Surveillance; Staging; Evaluation; Follow-up ID CIRCULATING TUMOR-CELLS; POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSTIC FOLLOW-UP; CLINICAL-ONCOLOGY; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; BONE METASTASES; ECONOMIC-EVALUATION; SURVIVAL; WOMEN AB In clinical practice, the surveillance and follow-up of patients with breast cancer (BC) is quite variable. At the 7th European Breast Cancer Conference, the ESO-MBC Task Force convened a series of lectures, followed by open debate, on the use of physical examination, imaging, and laboratory tests in patients with early-stage BC, and for restaging evaluations and follow-up among patients with MBC. Based on the available data, the Task Force recommends against intensive, routine radiologic or blood-based surveillance (with the exception of mammography) in patients with early-stage BC. As systemic therapies for MBC continue to improve, this question might be re-visited in the context of a carefully controlled clinical trial in specific BC subtypes. For patients with MBC, response to therapy should generally be assessed 2-3 months after initiation of treatment, and thereafter every 2-4 months for endocrine therapy or every 2-4 cycles for chemotherapy, depending on the dynamics of the disease, the location and extent of metastatic involvement, and type of treatment. Additional testing should be performed irrespective of the planned intervals if progression of disease is suspected (e.g. in the case of specific symptoms). Use of tumor markers is not recommended for surveillance of early-stage patients, but may be helpful in monitoring response to therapy in patients with metastatic disease. However, change in tumor markers alone should not be used for decision-making. Moving forward, enhanced efforts to document quality of life over time should be made in order to more fully evaluate the risk/benefit ratio of available options. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Thomssen, Christoph] Univ Halle Wittenberg, Dept Gynecol, D-06097 Halle, Saale, Germany. [Cardoso, Fatima] Champalimaud Canc Ctr, Breast Canc Unit, P-1400048 Lisbon, Portugal. [Cameron, David] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland. [Cufer, Tanja] Univ Clin Golnik, Golnik 4204, Slovenia. [Fallowfield, Lesley] Univ Sussex, Brighton & Sussex Med Sch, Sussex Hlth Outcomes Res & Educ Canc SHORE C, Falmer BN1 9RX, England. [Francis, Prudence A.] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic 8006, Australia. [Kyriakides, Stella] Europa Donna Cyprus, CY-1101 Nicosia, Cyprus. [Pagani, Olivia] Osped San Giovanni Bellinzona, Inst Oncol Southern Switzerland, CH-6500 Bellinzona, Switzerland. [Senkus, Elzbieta] Med Univ Gdansk, Dept Oncol & Radiotherapy, PL-80211 Gdansk, Poland. [Costa, Alberto] European Sch Oncol, Milan, Italy. [Costa, Alberto] Maugeri Fdn Breast Unit, Pavia, Italy. RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Canc Unit, Av Brasilia Doca Pedroucos, P-1400048 Lisbon, Portugal. EM nlin@partners.org; christoph.thomssen@medizin.uni-halle.de; fatimacardoso@fundacaochampalimaud.pt; d.cameron@ed.ac.uk; tanja.cufer@klinika-golnik.si; LJ.Fallowfield@Sussex.ac.uk; prue.francis@petermac.org; cysky@cytanet.com.cy; olivia.pagani@eoc.ch; elsenkus@gumed.edu.pl; acosta@eso.net; ewiner@partners.org RI Francis, Prudence/J-4003-2012; OI Fallowfield, Lesley/0000-0002-3328-4447; Senkus, Elzbieta/0000-0001-6855-397X; Gligorov, Joseph/0000-0002-9900-6386; Fallowfield, Lesley/0000-0003-0577-4518; Cardoso, Fatima/0000-0002-6692-2249 FU European School of Oncology FX This work was supported by the European School of Oncology. NR 71 TC 26 Z9 27 U1 0 U2 25 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD JUN PY 2013 VL 22 IS 3 BP 203 EP 210 DI 10.1016/j.breast.2013.03.006 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 151XE UT WOS:000319492900001 PM 23601761 ER PT J AU Nahleh, ZA Lin, NU Wolff, AC Cardoso, F AF Nahleh, Zeina A. Lin, Nancy U. Wolff, Antonio C. Cardoso, Fatima CA BIG-NABCG Collaboration TI Perceptions and needs of women with metastatic breast cancer: A focus on clinical trials SO BREAST LA English DT Article DE Perceptions; Metastatic; Breast; Cancer; BIG-NABCG ID SURVIVAL AB Many patients are living longer with Metastatic Breast Cancer (MBC) than ever before. However, complete responses remain uncommon, and progression of disease is often inevitable. The experience of living with MBC exposes patients to a wide variety of clinical, psychological, social and spiritual issues. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs, experiences, and perceptions of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of these patients. Fortunately, the tide is turning. This communication represents a joint effort of the Breast International Group and the National Cancer Institute (NCI)-sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions and needs of patients living with MBC and current obstacles facing them, and recommends strategies for better addressing some of these unmet needs. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Nahleh, Zeina A.] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wolff, Antonio C.] Johns Hopkins Kimmel Comprehens Canc Ctr, Breast Canc Program, Baltimore, MD 21287 USA. [Cardoso, Fatima] Champalimaud Canc Ctr, P-1400048 Lisbon, Portugal. RP Nahleh, ZA (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, 4800 Alberta Ave, El Paso, TX 79905 USA. EM Zeina.nahleh@ttuhsc.edu; Nancy_Lin@dfci.harvard.edu; awolff@jhmi.edu; fatimacardoso@fundacaochampalimaud.pt OI Wolff, Antonio/0000-0003-3734-1063; Cardoso, Fatima/0000-0002-6692-2249 FU NCI NIH HHS [P30 CA006973] NR 22 TC 2 Z9 2 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD JUN PY 2013 VL 22 IS 3 BP 370 EP 373 DI 10.1016/j.breast.2013.02.017 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 151XE UT WOS:000319492900027 PM 23535510 ER PT J AU Picaud, S Da Costa, D Thanasopoulou, A Filippakopoulos, P Fish, PV Philpott, M Fedorov, O Brennan, P Bunnage, ME Owen, DR Bradner, JE Taniere, P O'Sullivan, B Muller, S Schwaller, J Stankovic, T Knapp, S AF Picaud, Sarah Da Costa, David Thanasopoulou, Angeliki Filippakopoulos, Panagis Fish, Paul V. Philpott, Martin Fedorov, Oleg Brennan, Paul Bunnage, Mark E. Owen, Dafydd R. Bradner, James E. Taniere, Philippe O'Sullivan, Brendan Mueller, Susanne Schwaller, Juerg Stankovic, Tatjana Knapp, Stefan TI PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains SO CANCER RESEARCH LA English DT Article ID BONE-MARROW-CELLS; C-MYC; AURORA-B; KINASE INHIBITORS; STRUCTURAL BASIS; EXPRESSION; CANCER; BRD4; RECOGNITION; LEUKEMIA AB Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT) are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression. BET proteins are recruited on transcriptionally active chromatin via their two N-terminal bromodomains (BRD), a protein interaction module that specifically recognizes acetylated lysine residues in histones H3 and H4. Inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer. Here, we present a potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails. Cocrystal structures showed that PFI-1 acts as an acetyl-lysine (K-ac) mimetic inhibitor efficiently occupying the K-ac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G(1) cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Intriguingly, cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target. (C) 2013 AACR. C1 [Picaud, Sarah; Filippakopoulos, Panagis; Philpott, Martin; Fedorov, Oleg; Brennan, Paul; Mueller, Susanne; Knapp, Stefan] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, Oxon, England. [Knapp, Stefan] Univ Oxford, Nuffield Dept Clin Med, Target Discovery Inst, Oxford OX3 7DQ, Oxon, England. [Da Costa, David; Stankovic, Tatjana] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England. [Taniere, Philippe; O'Sullivan, Brendan] Queen Elizabeth Med Ctr, Dept Cellular Pathol, Birmingham, W Midlands, England. [Fish, Paul V.; Bunnage, Mark E.; Owen, Dafydd R.] Pfizer Worldwide R&D, Pfizer Worldwide Med Chem, Sandwich, Kent, England. [Thanasopoulou, Angeliki; Schwaller, Juerg] Univ Basel, Dept Biomed, Lab Childhood Leukemia, CH-4031 Basel, Switzerland. [Thanasopoulou, Angeliki; Schwaller, Juerg] Univ Basel, Childrens Hosp, CH-4031 Basel, Switzerland. [Knapp, Stefan] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Knapp, S (reprint author), Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, Oxon, England. EM j.schwaller@unibas.ch; t.stankovic@bham.ac.uk; stefan.knapp@sgc.ox.ac.uk RI Fedorov, Oleg/B-6412-2014; schwaller, juerg/A-3044-2016; OI Fedorov, Oleg/0000-0001-9004-1815; Filippakopoulos, Panagis/0000-0002-1515-1317; Knapp, Stefan/0000-0001-5995-6494; Muller-Knapp, Susanne/0000-0003-2402-4157 FU Wellcome Trust Career-Development Fellowship [095751/Z/11/Z]; Gertrude von Meissner Foundation; Swiss National Research Foundation (SNF) [31003A-130661]; Swiss Cancer League [OCS02357-2009]; Swiss Bridge Award FX S. Picaud, M. Philpott, O. Fedorov, P. Brennan, S. Muller, and S. Knapp are supported by the SGC, a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canada Foundation for Innovation, Genome Canada, GlaxoSmithKline, Pfizer, Eli Lilly, Takeda, AbbVie, the Novartis Research Foundation, the Ontario Ministry of Research and Innovation, and the Wellcome Trust. P. Filippakopoulos is supported by a Wellcome Trust Career-Development Fellowship (095751/Z/11/Z). J. Schwaller was supported by the Gertrude von Meissner Foundation, the Swiss National Research Foundation (SNF, 31003A-130661), the Swiss Cancer League (OCS02357-2009), and the Swiss Bridge Award. NR 46 TC 87 Z9 88 U1 5 U2 45 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 JUN 1 PY 2013 VL 73 IS 11 BP 3336 EP 3346 DI 10.1158/0008-5472.CAN-12-3292 PG 11 WC Oncology SC Oncology GA 155GV UT WOS:000319736800015 PM 23576556 ER PT J AU Price, RL Song, J Bingmer, K Kim, TH Yi, JY Nowicki, MO Mo, XK Hollon, T Murnan, E Alvarez-Breckenridge, C Fernandez, S Kaur, B Rivera, A Oglesbee, M Cook, C Chiocca, EA Kwon, CH AF Price, Richard L. Song, Jieun Bingmer, Katherine Kim, Tae Hyong Yi, Ji-Yeun Nowicki, Michal O. Mo, Xiaokui Hollon, Todd Murnan, Eric Alvarez-Breckenridge, Christopher Fernandez, Soledad Kaur, Balveen Rivera, Andreana Oglesbee, Michael Cook, Charles Chiocca, E. Antonio Kwon, Chang-Hyuk TI Cytomegalovirus Contributes to Glioblastoma in the Context of Tumor Suppressor Mutations SO CANCER RESEARCH LA English DT Article ID NEURAL STEM/PROGENITOR CELLS; MURINE CYTOMEGALOVIRUS; BRAIN-TUMORS; DNA-SEQUENCE; IN-VIVO; INFECTION; ASTROCYTOMAS; ASSOCIATION; PATHWAYS; GLIOMAS AB To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1(loxP/+); Trp53(-/+) genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans. (C) 2013 AACR. C1 [Price, Richard L.; Song, Jieun; Bingmer, Katherine; Kim, Tae Hyong; Yi, Ji-Yeun; Hollon, Todd; Murnan, Eric; Alvarez-Breckenridge, Christopher; Kaur, Balveen; Chiocca, E. Antonio; Kwon, Chang-Hyuk] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Neurooncol Ctr, Columbus, OH 43210 USA. [Song, Jieun; Kim, Tae Hyong; Yi, Ji-Yeun; Murnan, Eric; Kwon, Chang-Hyuk] Ohio State Univ, Med Ctr, Solid Tumor Program, James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Mo, Xiaokui; Fernandez, Soledad] Ohio State Univ, Med Ctr, Ctr Biostat, Columbus, OH 43210 USA. [Rivera, Andreana] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Oglesbee, Michael] Ohio State Univ, Med Ctr, Dept Vet Biosci, Columbus, OH 43210 USA. [Cook, Charles] Ohio State Univ, Med Ctr, Dept Surg, Columbus, OH 43210 USA. [Nowicki, Michal O.; Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurol Surg, Boston, MA 02115 USA. [Nowicki, Michal O.; Chiocca, E. Antonio] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Brigham & Womens Faulkner Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM EAChiocca@partners.org; Chang-Hyuk.Kwon@osumc.edu RI Cook, Charles/D-5574-2009; Kwon, Chang-hyuk/E-3450-2011; kaur, Balveen/E-3355-2011; OI Cook, Charles/0000-0003-4446-3616; SONG, JIEUN/0000-0001-7886-1765 FU NIH [P30NS045758-06, R01NS064607]; Viral Oncology Program Grant; Dardinger Neuro-oncology Fund; Jeffrey Thomas Hayden Foundation; OSU MBCG Program grant; OSU CCC Start-up Fund FX This study was funded by NIH P30NS045758-06, R01NS064607 (B. Kaur), a Viral Oncology Program Grant, the Dardinger Neuro-oncology Fund, the Jeffrey Thomas Hayden Foundation (E.A. Chiocca), OSU MBCG Program grant (E.A. Chiocca and C.-H. Kwon), and OSU CCC Start-up Fund (C.-H. Kwon) NR 40 TC 22 Z9 22 U1 0 U2 9 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 JUN 1 PY 2013 VL 73 IS 11 BP 3441 EP 3450 DI 10.1158/0008-5472.CAN-12-3846 PG 10 WC Oncology SC Oncology GA 155GV UT WOS:000319736800024 PM 23729642 ER PT J AU Pender-Cudlip, MC Krag, KJ Martini, D Yu, J Guidi, A Skinner, SS Zhang, Y Qu, XY He, CW Xu, Y Qian, SY Kang, JX AF Pender-Cudlip, Marilla C. Krag, Karen J. Martini, David Yu, Jeanne Guidi, Anthony Skinner, Sandy S. Zhang, Yu Qu, Xiying He, Chengwei Xu, Yi Qian, Steven Y. Kang, Jing X. TI Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue SO CANCER SCIENCE LA English DT Article ID FATTY-ACIDS; EICOSAPENTAENOIC ACID; DELTA-6 DESATURASE; GENETIC-VARIANTS; DIETARY N-3; RAT-LIVER; METABOLISM; DISEASE; RISK; MICE AB Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE2), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE2 levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE2 levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P<0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P<0.001), and was higher in ER than in ER+ patients, indicating genotype-related trends. Similarly, PGE2 levels were increased in cancerous tissue, particularly in ER patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE2 levels are increased in breast tumors, particularly those of the ER genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment. C1 [Pender-Cudlip, Marilla C.; Zhang, Yu; Qu, Xiying; He, Chengwei; Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol,Dept Med, Boston, MA 02115 USA. [Krag, Karen J.; Martini, David; Yu, Jeanne] Mass Gen North Shore Canc Ctr, Danvers, MA USA. [Guidi, Anthony; Skinner, Sandy S.] North Shore Med Ctr, Salem, MA USA. [Xu, Yi; Qian, Steven Y.] N Dakota State Univ, Fargo, ND 58105 USA. RP Kang, JX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol,Dept Med, Boston, MA 02115 USA. EM kang.jing@mgh.harvard.edu FU READ Charitable Trust (Salem, MA, USA) FX We thank the READ Charitable Trust (Salem, MA, USA) for their generous financial support of this study and Erin D. Gleason for manuscript edits and preparation. NR 40 TC 15 Z9 16 U1 2 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JUN PY 2013 VL 104 IS 6 BP 760 EP 764 DI 10.1111/cas.12129 PG 5 WC Oncology SC Oncology GA 150PZ UT WOS:000319404600015 PM 23414387 ER PT J AU Todoran, TM Zile, MR AF Todoran, Thomas M. Zile, Michael R. TI Neuromodulation Device Therapy for Treatment of Hypertensive Heart Disease SO CIRCULATION JOURNAL LA English DT Review DE Baroreflex activation therapy; Hypertension; Spinal cord stimulation; Sympathetic renal denervation; Vagal nerve stimulation ID RENAL SYMPATHETIC DENERVATION; BAROREFLEX ACTIVATION THERAPY; LEFT-VENTRICULAR HYPERTROPHY; DRUG-RESISTANT HYPERTENSION; LOWERS BLOOD-PRESSURE; RHEOS PIVOTAL TRIAL; LEFT ATRIAL VOLUME; BARORECEPTOR STIMULATION; MULTICENTER FEASIBILITY; DIASTOLIC DYSFUNCTION AB Hypertensive heart disease (HHD) is the leading cause of mortality and morbidity in the United States. Despite the availability of medical therapy it remains a challenge to treat. Autonomic nervous system imbalance resulting in overactivity of the sympathetic nervous system and under activity of the parasympathetic nervous system is integral in the development of hypertension and ultimately the development of HHD. Emerging data suggest that neuromodulation device therapy for treatment of HHD is promising. C1 Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Todoran, TM (reprint author), 25 Courtenay Dr,MSC 592, Charleston, SC 29425 USA. EM todoran@musc.edu FU CVRx; Medtronic FX T.M.T. has nothing to disclose. M.R.Z. is a consultant for and receives research funds from CVRx and Medtronic. NR 47 TC 3 Z9 4 U1 1 U2 8 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD JUN PY 2013 VL 77 IS 6 BP 1351 EP 1363 DI 10.1253/circj.CJ-13-0390 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 154CG UT WOS:000319648500001 PM 23657125 ER PT J AU Warren, SR Raisch, DW Campbell, HM Guarino, PD Kaufman, JS Petrokaitis, E Goldfarb, DS Gaziano, JM Jamison, RL AF Warren, Stuart R. Raisch, Dennis W. Campbell, Heather M. Guarino, Peter D. Kaufman, James S. Petrokaitis, Elizabeth Goldfarb, David S. Gaziano, J. Michael Jamison, Rex L. CA Vet Affairs Site Investigators TI Medication adherence assessment in a clinical trial with centralized follow-up and direct-to-patient drug shipments SO CLINICAL TRIALS LA English DT Article ID SELF-REPORT; THERAPY; AGREEMENT AB Background Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel. Purpose To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up. Methods Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (>= 85.7%) and liberal (>= 71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures. Results Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p = 0.005 for the stringent and p = 0.003 for the liberal definition; questionnaire: p = 0.002 for both adherence definitions). Limitations Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias. Conclusions Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required. C1 [Warren, Stuart R.; Raisch, Dennis W.; Campbell, Heather M.] VA Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM 87106 USA. [Warren, Stuart R.; Raisch, Dennis W.; Campbell, Heather M.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Guarino, Peter D.; Petrokaitis, Elizabeth] VA Connecticut Healthcare Syst, VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Kaufman, James S.] VA Boston Healthcare Syst, Renal Sect, Boston, MA USA. [Kaufman, James S.] Boston Univ, Sch Med, Renal Sect, Boston, MA 02118 USA. [Goldfarb, David S.] New York Harbor Healthcare Syst, Nephrol Sect, New York, NY USA. [Goldfarb, David S.] NYU, Sch Med, Nephrol Sect, New York, NY USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat MAVERI, Boston, MA USA. [Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Jamison, Rex L.] Vet Affairs VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Jamison, Rex L.] Stanford Univ, Dept Med, Sch Med, Div Nephrol, Stanford, CA 94305 USA. RP Warren, SR (reprint author), VA Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, 2401 Ctr Ave SE, Albuquerque, NM 87106 USA. EM stuart.warren@va.gov OI Goldfarb, David/0000-0002-9215-1273 FU Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development; PamLab LLC; Abbott Laboratories FX This study was sponsored by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and was supported in part by PamLab LLC and Abbott Laboratories. NR 29 TC 2 Z9 2 U1 0 U2 9 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 JUN PY 2013 VL 10 IS 3 BP 441 EP 448 DI 10.1177/1740774511410331 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 148FI UT WOS:000319228200010 PM 21813583 ER PT J AU Kuruvilla, MS Green, JR Ayaz, H Murman, DL AF Kuruvilla, Mili S. Green, Jordan R. Ayaz, Hasan Murman, Daniel L. TI Neural correlates of cognitive decline in ALS: An fNIRS study of the prefrontal cortex SO COGNITIVE NEUROSCIENCE LA English DT Article DE ALS; Cognition; fNIRS; Functional near infrared spectroscopy; N-back ID AMYOTROPHIC-LATERAL-SCLEROSIS; WORKING-MEMORY; AUDITORY-CORTEX; VERBAL FLUENCY; BRAIN; RETRIEVAL; WORKLOAD; MRI; PET AB Functional near infrared spectroscopy (fNIRS) is a clinically feasible functional neuroimaging modality for detecting early cortical changes due to neurodegenerative diseases that affect cognition. The objective of this preliminary investigation was to test for reduced prefrontal activity in persons with cognitive impairments due to amyotrophic lateral sclerosis (ALS). Participants were required to complete two N-back working memory tasks of increasing complexity during fNIRS recordings. Five participants with ALS and age- and gender-matched healthy participants comprised the experimental and control groups, respectively. Significant reductions in prefrontal oxygenation levels were observed for the left and right hemispheres in the ALS group compared to the control group. Reduced prefrontal activation despite intact behavioral performance for a working memory task may suggest early neuroanatomical, neurophysiological and/or compensatory mechanisms in affected individuals. The fNIRS-derived oxygenation measure shows promise as a sensitive neural marker to identify early neuropsychological impairments due to ALS. C1 [Kuruvilla, Mili S.] Univ Nebraska Med Ctr, Munroe Meyer Inst Genet & Rehabil, Omaha, NE 68198 USA. [Green, Jordan R.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Ayaz, Hasan] Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA. [Murman, Daniel L.] Univ Nebraska Med Ctr, Dept Neurol Sci, Omaha, NE 68198 USA. RP Kuruvilla, MS (reprint author), Univ Nebraska Med Ctr, Munroe Meyer Inst Genet & Rehabil, 985450 Nebraska Med Ctr, Omaha, NE 68198 USA. EM mili.kuruvilla@unmc.edu OI Kuruvilla-Dugdale, Mili/0000-0001-7900-2364; Ayaz, Hasan/0000-0001-5514-2741 FU Barkley Trust; NIH-NIDCD [R01 DC009890]; Munroe Meyer Institute of Genetics and Rehabilitation FX This research was funded by the Barkley Trust, an NIH-NIDCD grant R01 DC009890, and a seed grant from the Munroe Meyer Institute of Genetics and Rehabilitation. The authors would like to thank Cynthia Didion, Lori Synhorst, Jun Wang, and Suyash Joshi for their help with data collection and analysis. NR 37 TC 1 Z9 1 U1 2 U2 12 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PD JUN 1 PY 2013 VL 4 IS 2 BP 115 EP 121 DI 10.1080/17588928.2013.797889 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 151YA UT WOS:000319495100008 PM 24073736 ER PT J AU Fonseca, R Pitman, MB AF Fonseca, R. Pitman, M. B. TI Lymphangioma of the pancreas: a multimodal approach to pre-operative diagnosis SO CYTOPATHOLOGY LA English DT Article DE EUS-FNA; endoscopic ultrasound-guided FNA; lymphangioma; pancreas; multimodal diagnosis; cytology ID CYST-FLUID ANALYSIS; FINE-NEEDLE-ASPIRATION; PAPILLARY MUCINOUS NEOPLASMS; EUS-GUIDED FNA; DIFFERENTIAL-DIAGNOSIS; LESIONS; MANAGEMENT; CYSTADENOMA; CYTOLOGY AB Background: Lymphangioma of the pancreas is an extremely rare benign tumour of lymphatic origin, with only four cases diagnosed by EUS-FNA reported to date. Methods and materials: Five cases of either cytologically or histologically diagnosed pancreatic lymphangioma with pre-operative cytological analysis by EUS-FNAC were reviewed. Results: All patients were female, with a mean age of 56.4years. By imaging, the cystic lesions ranged in size from 2 to 7cm (mean 4.5cm) and were mainly located in the head of the pancreas. All cysts had thin walls and no cyst demonstrated a mural nodule. Diagnosis based on imaging features was benign in all cases due to the absence of high-risk features. Four samples were sent for biochemical analysis, which showed low CEA levels (range, <0.519.4ng/ml; mean, 5.45ng/ml) and CA 19.9 and CA 72.4 levels within normal range. All cyst fluids showed numerous small lymphocytes with no atypia; no epithelial cells were present, including no gastrointestinal contamination. Flow cytometry in two cases showed T lymphocytes with a mature phenotype. Surgical resection in two patients confirmed the cytological diagnosis. Benign clinical follow-up was available in three patients at 2, 3 and 3.5years. Conclusion: A multimodal approach to cytological diagnosis (combining clinical, radiological and cyst fluid gross, biochemical and cytological characteristics) can lead to the diagnosis of this cystic neoplasm and distinguish it from other more common cysts in the pancreas, potentially avoiding the need for unnecessary surgery. C1 [Fonseca, R.] Inst Portugues Oncol Francisco Gentil, Dept Pathol, P-1099023 Lisbon, Portugal. [Pitman, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Labs, Boston, MA USA. RP Fonseca, R (reprint author), Inst Portugues Oncol Francisco Gentil, Dept Pathol, R Prof Lima Basto, P-1099023 Lisbon, Portugal. EM ricardo.fonseca@netcabo.pt NR 26 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0956-5507 J9 CYTOPATHOLOGY JI Cytopathology PD JUN PY 2013 VL 24 IS 3 BP 172 EP 176 DI 10.1111/j.1365-2303.2011.00897.x PG 5 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 151OM UT WOS:000319469900004 PM 21810124 ER PT J AU Zhang, Y Harrison, JM Nateras, OS Chalfin, S Duong, TQ AF Zhang, Yi Harrison, Joseph M. Nateras, Oscar San Emeterio Chalfin, Steven Duong, Timothy Q. TI Decreased retinal-choroidal blood flow in retinitis pigmentosa as measured by MRI SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article DE Retinal diseases; Magnetic resonance imaging; Electroretinography; Retinal degeneration ID MANGANESE-ENHANCED MRI; RAT RETINA; FUNCTIONAL MRI; MOUSE MODEL; MORPHOLOGICAL-CHANGES; ABYSSINIAN CATS; VASCULAR LAYERS; ANATOMICAL MRI; IN-VIVO; DEGENERATION AB To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP). MRI studies were performed in 6 RP patients (29-67 years) and 5 healthy volunteers (29-64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial spin-labeling technique at 0.5 x 0.8 x 6.0 mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed. Basal BF in the posterior retinal-choroid was 142 +/- A 16 ml/100ml/min (or 1.14 +/- A 0.13 mu l/mm(2)/min) in the control group and was 70 +/- 19 ml/100ml/min (or 0.56 +/- A 0.15 mu l/mm(2)/min) in the RP group. Retinal-choroidal BF was significantly reduced by 52 +/- A 8 % in RP patients compared to controls (P < 0.05). ERG a- and b-wave amplitudes of RP patients were reduced, and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P < 0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2). This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal-choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG. C1 [Zhang, Yi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Zhang, Yi; Nateras, Oscar San Emeterio; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Harrison, Joseph M.; Chalfin, Steven; 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 Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU Clinical Translational Science Award Pilot Grant; Translational Technology Resource grant [UL1TR000149]; NIH/NEI [R01 EY014211, EY018855]; Department of Veterans Affairs MERIT awards; Translational Science Training award through the University of Texas System Graduate Program Initiative FX This work was supported by a Clinical Translational Science Award Pilot Grant and a Translational Technology Resource grant (parent grant UL1TR000149), NIH/NEI (R01 EY014211 and EY018855), and Department of Veterans Affairs MERIT awards to TQD. YZ was supported by a Translational Science Training award through the University of Texas System Graduate Program Initiative. NR 65 TC 14 Z9 15 U1 0 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD JUN PY 2013 VL 126 IS 3 BP 187 EP 197 DI 10.1007/s10633-013-9374-1 PG 11 WC Ophthalmology SC Ophthalmology GA 151QX UT WOS:000319476400002 PM 23408312 ER PT J AU Moon, HS Dalamaga, M Kim, SY Polyzos, SA Hamnvik, OP Magkos, F Paruthi, J Mantzoros, CS AF Moon, Hyun-Seuk Dalamaga, Maria Kim, Sang-Yong Polyzos, Stergios A. Hamnvik, Ole-Petter Magkos, Faidon Paruthi, Jason Mantzoros, Christos S. TI Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals SO ENDOCRINE REVIEWS LA English DT Review ID FATTY LIVER-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; HEPATIC STELLATE CELLS; DIET-INDUCED OBESITY; RECOMBINANT HUMAN LEPTIN; TYROSINE-PHOSPHATASE SHP-2; VIRUS-INFECTED PATIENTS; METHIONYL HUMAN LEPTIN; EMERGING CLINICAL-APPLICATIONS; TERM METRELEPTIN TREATMENT AB Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes. C1 [Moon, Hyun-Seuk; Kim, Sang-Yong; Hamnvik, Ole-Petter; Magkos, Faidon; Paruthi, Jason; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Dalamaga, Maria] Univ Athens, Sch Med, Attikon Gen Univ Hosp, Dept Clin Biochem, Athens 15784, Greece. [Kim, Sang-Yong] Chosun Univ, Sch Med, Div Endocrinol & Metab, Kwangju 501717, South Korea. [Polyzos, Stergios A.] Aristotle Univ Thessaloniki, Ippokrat Hosp, Med Clin 2, Thessaloniki 11527, Greece. [Hamnvik, Ole-Petter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Endocrinol Sect, Boston, MA 02118 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, JP9B52A,150 South Huntington Ave, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu RI Hamnvik, Ole-Petter/D-1719-2011; Moon, Hyun-Seuk/G-8576-2015; OI Moon, Hyun-Seuk/0000-0002-5216-2090; Polyzos, Stergios/0000-0001-9232-4042; Dalamaga, Maria/0000-0002-7008-388X FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913, AG032030]; VA Merit award [10684957]; Beth Israel Deaconess Medical Center FX The Mantzoros laboratory is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants 58785, 79929, 81913, and AG032030 and a VA Merit award (Grant 10684957). The Mantzoros Laboratory is also supported by a discretionary grant from Beth Israel Deaconess Medical Center. NR 321 TC 74 Z9 80 U1 0 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2013 VL 34 IS 3 BP 377 EP 412 DI 10.1210/er.2012-1053 PG 36 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 154KN UT WOS:000319674300003 PM 23475416 ER PT J AU Olivry, T Bizikova, P Paps, JS Dunston, S Lerner, EA Yosipovitch, G AF Olivry, Thierry Bizikova, Petra Paps, Judy S. Dunston, Stan Lerner, Ethan A. Yosipovitch, Gil TI Cowhage can induce itch in the atopic dog SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE canine; dog; itch; model; pruritus ID PROTEINASE-ACTIVATED RECEPTOR-2; DERMATITIS; SKIN; HISTAMINE; AGENTS; MODEL AB Itch is a cardinal symptom of atopic dermatitis in humans and dogs. Until now, experimental induction of itch in dogs has proven difficult. The objectives of this study were to determine whether protease-rich spicules, protein extracts and the protease mucunain of the tropical legume cowhage provoked itch and inflammation when rubbed onto canine skin. Native spicules variably induced itch manifestations in about half of the dogs, while challenges with protease-deactivated spicules remained negative. The epicutaneous application of cowhage extract and mucunain after microneedle roller usage also induced pruritus and inflammation. Importantly, there was an interindividual inconsistency in pruritus and inflammation induction and also marked differences in pruritus intensity after challenge. In conclusion, cowhage spicules, protein-rich extracts and mucunain can all induce pruritus and inflammation in dogs as in other species, but the inconsistency of provocation is currently a limitation of this challenge type for future studies of pruritus in dogs. C1 [Olivry, Thierry; Bizikova, Petra; Paps, Judy S.; Dunston, Stan] NC State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC USA. [Olivry, Thierry; Bizikova, Petra] NC State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC USA. [Lerner, Ethan A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Yosipovitch, Gil] Wake Forest Univ, Med Ctr, Dept Dermatol, Winston Salem, NC 27109 USA. RP Olivry, T (reprint author), N Carolina State Univ, Coll Vet Med, Dept Clin Sci, 1060 Williams Moore Dr, Raleigh, NC 27607 USA. EM tolivry@ncsu.edu FU Novartis Animal Health FX This study was funded by Novartis Animal Health. The authors thank Dr. Kristine Rossbach for her help during pilot challenges. The author also thanks GY and EL who designed the study; JS, PB and SD who performed the research and analysed the data; and PB, GY and EL who wrote the manuscript. NR 15 TC 4 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JUN PY 2013 VL 22 IS 6 BP 435 EP 437 DI 10.1111/exd.12158 PG 3 WC Dermatology SC Dermatology GA 151PE UT WOS:000319471800017 PM 23711071 ER PT J AU Sawyer, TK Wu, JC Sawyer, JR English, JM AF Sawyer, Tomi K. Wu, Joe C. Sawyer, Jonathon R. English, Jessie M. TI Protein kinase inhibitors: breakthrough medicines and the next generation SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Editorial Material DE kinase inhibitor; protein kinase; proteins; small-molecule ID DRUG AB In this issue of Expert Opinion on Investigational Drugs, several protein kinases families and pathways underlying cancer and other diseases are reviewed and several small molecule inhibitors that are in clinical trials are further described. Highlights of these reviews and drug evaluations are summarized in this editorial. C1 [Sawyer, Tomi K.] Aileron Therapeut, Cambridge, MA 02139 USA. [Wu, Joe C.] GlaxoSmithKline PLC, Cambridge, MA 02139 USA. [Sawyer, Jonathon R.] Providence Coll, Providence, RI 02908 USA. [English, Jessie M.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. RP Sawyer, TK (reprint author), Aileron Therapeut, Cambridge, MA 02139 USA. EM sawyerkrt@aol.com NR 14 TC 6 Z9 8 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2013 VL 22 IS 6 BP 675 EP 678 DI 10.1517/13543784.2013.804509 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 150TP UT WOS:000319414400001 PM 23705633 ER PT J AU Kurihara, T Jones, CN Yu, YM Fischman, AJ Watada, S Tompkins, RG Fagan, SP Irimia, D AF Kurihara, Tomohiro Jones, Caroline N. Yu, Yong-Ming Fischman, Alan J. Watada, Susumu Tompkins, Ronald G. Fagan, Shawn P. Irimia, Daniel TI Resolvin D2 restores neutrophil directionality and improves survival after burns SO FASEB JOURNAL LA English DT Article DE chemotaxis; microfluidics; inflammation; innate immunity; lipid mediators ID THERMAL-INJURY; D1; SEPSIS; INFECTION; MEDIATORS; TRAUMA; INFLAMMATION; MICE; RESOLUTION; MORTALITY AB Following severe burns and trauma injuries, the changes of neutrophil migratory phenotype are a double-edged sword. Activated neutrophils migrate into injured tissues and help contain microbial infections, but they can also enter normal tissues and damage vital organs. Depleting the neutrophils from circulation protects vital organs against neutrophil-induced damage but leaves the body exposed to infectious complications. Here we show that restoring normal neutrophil migratory phenotype in rats with burn injuries correlates with improved survival in a classical double-injury model of sequential burn and septic insults. We uncovered that the directionality of neutrophils from burned rats can be restored both in vitro by 1 nM resolvin D2 (RvD2) and in vivo by RvD2 for 7 d, 25 ng/kg body mass (8-10 ng/rat). Restoring neutrophil directionality dramatically increases survival after a second septic insult at d 9 postburn. Survival of RvD2-treated animals increases from 0 to 100% after lipopolysaccharide injection and is extended by 1 wk after cecal ligation. Survival does not significantly increase when the restoration of neutrophil directionality is incomplete, following shorter regimens of RvD2. We conclude that restoring neutrophil directionality using RvD2 could have prophylactic value and delay lethal complications after burn injuries.-Kurihara T., Jones, C. N., Yu, Y.-M., Fischman, A. J., Watada, S., Tompkins, R. G., Fagan, S. P., Irimia, D. Resolvin D2 restores neutrophil directionality and improves survival after burns. C1 [Kurihara, Tomohiro; Jones, Caroline N.; Yu, Yong-Ming; Fischman, Alan J.; Watada, Susumu; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel] Shriners Hosp Children, Boston, MA USA. [Kurihara, Tomohiro; Jones, Caroline N.; Yu, Yong-Ming; Watada, Susumu; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jones, Caroline N.; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA USA. [Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA USA. RP Irimia, D (reprint author), MGH CNY, 114 16th St,1404, Boston, MA 02129 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU Shriners Burns Hospital; U.S. National Institutes of Health [GM-092804, GM-007035, DE-019938] FX This work was supported in part by funds from Shriners Burns Hospital and U.S. National Institutes of Health grants GM-092804, GM-007035, and DE-019938. NR 44 TC 30 Z9 30 U1 0 U2 11 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 JUN PY 2013 VL 27 IS 6 BP 2270 EP 2281 DI 10.1096/fj.12-219519 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 154II UT WOS:000319667600017 PM 23430978 ER PT J AU Sachse, CC Kim, YH Agsten, M Huth, T Alzheimer, C Kovacs, DM Kim, DY AF Sachse, Carolyn C. Kim, Young Hye Agsten, Marianne Huth, Tobias Alzheimer, Christian Kovacs, Dora M. Kim, Doo Yeon TI BACE1 and presenilin/gamma-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels SO FASEB JOURNAL LA English DT Article DE MinK; MiRP; Alzheimer's disease; KCNQ1 ID LONG QT SYNDROME; ALZHEIMERS-DISEASE; BETA-SECRETASE; I-KS; SODIUM-CHANNELS; TARGETED DISRUPTION; MEDIATED CLEAVAGE; NEURONAL-ACTIVITY; ALPHA-SECRETASE; GAMMA-SECRETASE AB BACE1 and presenilin (PS)/gamma-secretase play a major role in Alzheimer's disease pathogenesis by regulating amyloid-beta peptide generation. We recently showed that these secretases also regulate the processing of voltage-gated sodium channel auxiliary beta-subunits and thereby modulate membrane excitability. Here, we report that KCNE1 and KCNE2, auxiliary subunits of voltage-gated potassium channels, undergo sequential cleavage mediated by either alpha-secretase and PS/gamma-secretase or BACE1 and PS/gamma-secretase in cells. Elevated alpha-secretase or BACE1 activities increased C-terminal fragment (CTF) levels of KCNE1 and 2 in human embryonic kidney (HEK293T) and rat neuroblastoma (B104) cells. KCNE-CTFs were then further processed by PS/gamma-secretase to KCNE intracellular domains. These KCNE cleavages were specifically blocked by chemical inhibitors of the secretases in the same cell models. We also verified our results in mouse cardiomyocytes and cultured primary neurons. Endogenous KCNE1- and KCNE2-CTF levels increased by 2- to 4-fold on PS/gamma-secretase inhibition or BACE1 overexpression in these cells. Furthermore, the elevated BACE1 activity increased KCNE1 processing and shifted KCNE1/KCNQ1 channel activation curve to more positive potentials in HEK cells. KCNE1/KCNQ1 channel is a cardiac potassium channel complex, and the positive shift would lead to a decrease in membrane repolarization during cardiac action potential. Together, these results clearly showed that KCNE1 and KCNE2 cleavages are regulated by BACE1 and PS/gamma-secretase activities under physiological conditions. Our results also suggest a functional role of KCNE cleavage in regulating voltage-gated potassium channels.-Sachse, C. C., Kim, Y. H., Agsten, M., Huth, T., Alzheimer, C., Kovacs, D. M., and Kim, D. Y. BACE1 and presenilin/gamma-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels. C1 [Sachse, Carolyn C.; Kim, Young Hye; Kovacs, Dora M.; Kim, Doo Yeon] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,Med Sch, Charlestown, MA USA. [Kim, Young Hye] Korea Basic Sci Inst, Div Mass Spectrometry Res, Ochang, South Korea. [Agsten, Marianne; Huth, Tobias; Alzheimer, Christian] Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany. RP Kim, DY (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM dkim@helix.mgh.harvard.edu OI Huth, Tobias/0000-0002-6414-8923 FU Cure Alzheimer's fund; U.S. National Institutes of Health/National Institute on Aging; Dr. Ernst und Anita Bauer-Stiftung; Johannes und Frieda Marohn-Stiftung FX The authors thank Stephanie Hartmann (University of Erlangen-Nurnberg) for her contribution in revising this manuscript and Dr. Jordan Tang (University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA) for BACE1 inhibitor DR9. This work is supported by grants from the Cure Alzheimer's fund to D.Y.K, the U.S. National Institutes of Health/National Institute on Aging to D.M.K and D.Y.K., the Dr. Ernst und Anita Bauer-Stiftung to S.H., and the Johannes und Frieda Marohn-Stiftung to T.H. and C.A. NR 48 TC 11 Z9 11 U1 0 U2 12 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 JUN PY 2013 VL 27 IS 6 BP 2458 EP 2467 DI 10.1096/fj.12-214056 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 154II UT WOS:000319667600033 PM 23504710 ER PT J AU Righi, V Constantinou, C Mintzopoulos, D Khan, N Mupparaju, SP Rahme, LG Swartz, HM Szeto, HH Tompkins, RG Tzika, AA AF Righi, Valeria Constantinou, Caterina Mintzopoulos, Dionyssios Khan, Nadeem Mupparaju, S. P. Rahme, Laurence G. Swartz, Harold M. Szeto, Hazel H. Tompkins, Ronald G. Tzika, A. Aria TI Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo P-31 nuclear magnetic resonance and electron paramagnetic resonance spectroscopy SO FASEB JOURNAL LA English DT Article DE physiology; molecular medicine; mice; mitochondria; oxidative stress ID INSULIN-RESISTANCE; INDUCED APOPTOSIS; NMR-SPECTROSCOPY; DOWN-REGULATION; PEPTIDE; INJURY; ACONITASE; METABOLISM; MODULATION; DYSFUNCTION AB Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy to noninvasively measure high-energy phosphate levels; mitochondrial aconitase activity measurements that directly correlate with TCA cycle flux, as measured by gas chromatography mass spectrometry (GC-MS); and electron paramagnetic resonance (EPR) to assess oxidative stress. At 6 h postburn, the oxidative ATP synthesis rate was increased 5-fold in burned mice given a single dose of SS-31 relative to untreated burned mice (P=0.002). Furthermore, SS-31 administration in burned animals decreased mitochondrial aconitase activity back to control levels. EPR revealed a recovery in redox status of the SS-31-treated burn group compared to the untreated burn group (P<0.05). Our multidisciplinary convergent results suggest that SS-31 promotes recovery of mitochondrial function after burn injury by increasing ATP synthesis rate, improving mitochondrial redox status, and restoring mitochondrial coupling. These findings suggest use of noninvasive in vivo NMR and complementary EPR offers an approach to monitor the effectiveness of mitochondrial protective agents in alleviating burn injury symptoms. C1 [Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, Boston, MA 02114 USA. [Constantinou, Caterina; Rahme, Laurence G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Surg Lab,Dept Surg, Boston, MA 02114 USA. [Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Rahme, Laurence G.; Tompkins, Ronald G.; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Burns, Boston, MA 02114 USA. [Righi, Valeria; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Righi, Valeria; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02114 USA. [Khan, Nadeem; Mupparaju, S. P.; Swartz, Harold M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch,Dept Diagnost Radiol, Electron Paramagnet Resonance EPR Ctr Viable Syst, Hanover, NH 03756 USA. [Szeto, Hazel H.] Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, 51 Blossom St,Rm 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu OI Righi, Valeria/0000-0003-2394-8462; Constantinou, Caterina/0000-0003-3589-0739 FU U.S. National Institute Institutes of Health (NIH) [P50GM021700]; Shriner's Hospital for Children [8893, 8892]; U.S. Defense Medical Research and Development Program (DMRDP) [DM103014] FX This work was supported in part by a U.S. National Institute Institutes of Health (NIH) center grant (P50GM021700) to R. G. T. (A. A. T., director of the NMR core), Shriner's Hospital for Children research grants to A. A. T. (8893) and L. G. R. (8892), and a research support grant (DM103014) from the U.S. Defense Medical Research and Development Program (DMRDP). The authors thank Dr. Alan J. Fischman for his advice. The authors also thank Dr. Ann Power Smith (Write Science Right, Las Vegas, NV, USA) for editorial assistance. Disclosure: the SS peptides technology has been licensed for commercial development to Stealth Peptides Inc. (Newton Centre, MA, USA) by the Cornell Research Foundation (CRF), and both CRF and H. H. S. have financial interests. NR 45 TC 6 Z9 6 U1 2 U2 9 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 JUN PY 2013 VL 27 IS 6 BP 2521 EP 2530 DI 10.1096/fj.12-220764 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 154II UT WOS:000319667600040 PM 23482635 ER PT J AU Avior, Y Bomze, D Ramon, O Nahmias, Y AF Avior, Yishai Bomze, David Ramon, Ory Nahmias, Yaakov TI Flavonoids as dietary regulators of nuclear receptor activity SO FOOD & FUNCTION LA English DT Review ID PROLIFERATOR-ACTIVATED RECEPTOR; PREGNANE X-RECEPTOR; OBESE ZUCKER RATS; CITRUS POLYMETHOXYLATED FLAVONES; ALPHA-INDEPENDENT MECHANISMS; APOLIPOPROTEIN-B SECRETION; CYP3A4 GENE-EXPRESSION; ESTROGEN-LIKE ACTIVITY; NITRIC-OXIDE SYNTHASE; BONE-MINERAL DENSITY AB Metabolic diseases such as obesity, type II diabetes, and dyslipidemia are a rising cause of mortality worldwide. The progression of many metabolic diseases is fundamentally regulated on the transcriptional level by a family of ligand-activated transcription factors, called nuclear receptors, which detect and respond to metabolic changes. Their role in maintaining metabolic homeostasis makes nuclear receptors an important pharmaceutical and dietary target. This review will present the growing evidence that flavonoids, natural secondary plant metabolites, are important regulators of nuclear receptor activity. Structural similarities between flavonoids and cholesterol derivatives combined with the promiscuous nature of most nuclear receptors provide a wealth of possibilities for pharmaceutical and dietary modulation of metabolism. While the challenges of bringing flavonoid-derived therapeutics to the market are significant, we consider this rapidly growing field to be an essential aspect of the functional food initiative and an important mine for pharmaceutical compounds. C1 [Avior, Yishai; Ramon, Ory; Nahmias, Yaakov] Hebrew Univ Jerusalem, Ctr Bioengn, Sch Engn & Comp Sci, IL-91904 Jerusalem, Israel. [Bomze, David; Nahmias, Yaakov] Hebrew Univ Jerusalem, Inst Life Sci, Dept Cell & Dev Biol, IL-91904 Jerusalem, Israel. [Nahmias, Yaakov] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Avior, Y (reprint author), Hebrew Univ Jerusalem, Ctr Bioengn, Sch Engn & Comp Sci, Edmond J Safra Campus Givat Ram,Silberman 3-512, IL-91904 Jerusalem, Israel. EM ynahmias@cs.huji.ac.il RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU European Research Council Starting Grant [TMIHCV 242699] FX This work was supported by the European Research Council Starting Grant (TMIHCV 242699). Resources were provided by National Institute of Diabetes and Digestive and Kidney Diseases (K01DK080241) and the Harvard Clinical Nutrition Research Center (P30-DK040561). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 209 TC 15 Z9 15 U1 2 U2 36 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2042-6496 EI 2042-650X J9 FOOD FUNCT JI Food Funct. PD JUN PY 2013 VL 4 IS 6 BP 831 EP 844 DI 10.1039/c3fo60063g PG 14 WC Biochemistry & Molecular Biology; Food Science & Technology SC Biochemistry & Molecular Biology; Food Science & Technology GA 152GE UT WOS:000319518700001 PM 23598551 ER PT J AU Chan, BK Abedon, ST Loc-Carrillo, C AF Chan, Benjamin K. Abedon, Stephen T. Loc-Carrillo, Catherine TI Phage cocktails and the future of phage therapy SO FUTURE MICROBIOLOGY LA English DT Review DE antibacterial; antibiotic resistance; bacteriophage; diversity of bacterial; pathogen; phage cocktail; polyphage ID ESCHERICHIA-COLI O157H7; IN-VIVO; PSEUDOMONAS-AERUGINOSA; BACTERIOPHAGE THERAPY; PERSONALIZED MEDICINE; CAMPYLOBACTER-JEJUNI; INFLUENZA VACCINES; BROILER-CHICKENS; HOST-RANGE; RESISTANCE AB Viruses of bacteria, known as bacteriophages or phages, were discovered nearly 100 years ago. Their potential as antibacterial agents was appreciated almost immediately, with the first 'phage therapy' trials predating Fleming's discovery of penicillin by approximately a decade. In this review, we consider phage therapy that can be used for treating bacterial infections in humans, domestic animals and even biocontrol in foods. Following an overview of the topic, we explore the common practice - both experimental and, in certain regions of the world, clinical - of mixing therapeutic phages into cocktails consisting of multiple virus types. We conclude with a discussion of the commercial and medical context of phage cocktails as therapeutic agents. In comparing off-the-shelf versus custom approaches, we consider the merits of a middle ground, which we deem 'modifiable'. Finally, we explore a regulatory framework for such an approach based on an influenza vaccine model. C1 [Chan, Benjamin K.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Abedon, Stephen T.] Ohio State Univ, Dept Microbiol, Mansfield, OH USA. [Loc-Carrillo, Catherine] Univ Utah, Dept Orthoped, Salt Lake City, UT 84112 USA. [Loc-Carrillo, Catherine] US Dept Vet Affairs, Hlth Care Syst, Salt Lake City, UT USA. RP Loc-Carrillo, C (reprint author), Univ Utah, Dept Orthoped, Salt Lake City, UT 84112 USA. EM c.loc.carrillo@hsc.utah.edu RI Loc Carrillo, Catherine/B-5461-2014 OI Loc Carrillo, Catherine/0000-0002-7265-1203 NR 103 TC 101 Z9 104 U1 29 U2 165 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 EI 1746-0921 J9 FUTURE MICROBIOL JI Future Microbiol. PD JUN PY 2013 VL 8 IS 6 BP 769 EP 783 DI 10.2217/FMB.13.47 PG 15 WC Microbiology SC Microbiology GA 151EH UT WOS:000319443000014 PM 23701332 ER PT J AU Schmeler, KM Ramirez, PT Reyes-Martinez, CA Chernofsky, MR del Carmen, MG Diaz-Montes, TP Padilla, L Tejada-Berges, T Tarraza, H Bermudez, A Trimble, EL AF Schmeler, Kathleen M. Ramirez, Pedro T. Reyes-Martinez, Cesar A. Chernofsky, Mildred R. del Carmen, Marcela G. Diaz-Montes, Teresa P. Padilla, Luis Tejada-Berges, Trevor Tarraza, Hector Bermudez, Adriana Trimble, Edward L. TI The Central America Gynecologic Oncology Education Program (CONEP): Improving gynecologic oncology education and training on a global scale SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID VISUAL INSPECTION; ACETIC-ACID C1 [Schmeler, Kathleen M.; Ramirez, Pedro T.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77230 USA. [Reyes-Martinez, Cesar A.] Hosp Gen San Juan, Dept Obstet & Ginecol, De Dios, Guatemala. [Chernofsky, Mildred R.] Sibley Mem Hosp, Sibley Ctr Gynecol Oncol & Adv Pelv Surg, Washington, DC USA. [del Carmen, Marcela G.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. [Diaz-Montes, Teresa P.] Johns Hopkins Med Inst, Dept Gynecol Oncol, Baltimore, MD USA. [Padilla, Luis] Univ New Mexico, Dept Gynecol Oncol, Albuquerque, NM 87131 USA. [Tejada-Berges, Trevor] Women & Infants Hosp Rhode Isl, Dept Gynecol Oncol, Providence, RI USA. [Tarraza, Hector] Maine Med Ctr, Dept Gynecol Oncol, Portland, ME USA. [Bermudez, Adriana] Buenos Aires Univ Hosp, Gynecol Oncol Unit, Buenos Aires, DF, Argentina. [Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. RP Schmeler, KM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, POB 301439, Houston, TX 77230 USA. EM kschmele@mdanderson.org NR 10 TC 6 Z9 6 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2013 VL 129 IS 3 BP 445 EP 447 DI 10.1016/j.ygyno.2013.03.013 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 151SK UT WOS:000319480300002 PM 23528927 ER PT J AU Taylor, WC King, KE Shegog, R Paxton, RJ Evans-Hudnall, GL Rempel, DM Chen, V Yancey, AK AF Taylor, Wendell C. King, Kathryn E. Shegog, Ross Paxton, Raheem J. Evans-Hudnall, Gina L. Rempel, David M. Chen, Vincent Yancey, Antronette K. TI Booster Breaks in the workplace: participants' perspectives on health-promoting work breaks SO HEALTH EDUCATION RESEARCH LA English DT Article ID PHYSICAL-ACTIVITY INTERVENTIONS; SEDENTARY BEHAVIOR; AFRICAN-AMERICAN; TIME; DETERMINANTS; MORTALITY; BELIEFS; OBESITY; LIFE AB Increasing sedentary work has been associated with greater cardiovascular and metabolic risk, as well as premature mortality. Interrupting the sedentary workday with health-promoting work breaks can counter these negative health effects. To examine the potential sustainability of work-break programs, we assessed the acceptance of these breaks among participants in a Booster Break program. We analyzed qualitative responses from 35 participants across five worksites where one 15-min physical activity break was taken each workday. Two worksites completed a 1-year intervention and three worksites completed a 6-month intervention. Responses to two open-ended questions about the acceptance and feasibility of Booster Breaks were obtained from a survey administered after the intervention. Three themes for benefits and two themes for barriers were identified. The benefit themes were (i) reduced stress and promoted enjoyment, (ii) increased health awareness and facilitated behavior change, and (iii) enhanced workplace social interaction. The barrier themes were the need for (iv) greater variety in Booster Break routines and (v) greater management support. This study provides empirical support for the acceptance and feasibility of Booster Breaks during the workday. Emphasizing the benefits and minimizing the barriers are strategies that can be used to implement Booster Breaks in other workplaces. C1 [Taylor, Wendell C.; King, Kathryn E.; Chen, Vincent] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA. [Shegog, Ross] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA. [Paxton, Raheem J.] Univ Texas MD Anderson Canc Ctr, Dorothy I Height Ctr Hlth Equ & Evaluat Res D CHE, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Evans-Hudnall, Gina L.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Rempel, David M.] Univ Calif San Francisco, Div Occupat & Environm Med, San Francisco, CA 94143 USA. [Rempel, David M.] Univ Calif Berkeley, Ergon Program, Dept Bioengn, Richmond, CA 94804 USA. [Yancey, Antronette K.] UCLA Fielding Sch Publ Hlth, UCLA Kaiser Permanente Ctr Hlth Equ, Dept Hlth Serv, Los Angeles, CA 90095 USA. RP Taylor, WC (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, 7000 Fannin St,Suite 2670, Houston, TX 77030 USA. EM Wendell.C.Taylor@uth.tmc.edu OI Paxton, Raheem/0000-0001-9430-7051 FU NCI NIH HHS [K01 CA158000]; NINR NIH HHS [R03NR10291] NR 40 TC 8 Z9 8 U1 2 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD JUN PY 2013 VL 28 IS 3 BP 414 EP 425 DI 10.1093/her/cyt001 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 153YP UT WOS:000319639000005 PM 23466367 ER PT J AU Schliamser, JE Kadish, AH Subacius, H Shalaby, A Schaechter, A Levine, J Goldberger, JJ AF Schliamser, Jorge E. Kadish, Alan H. Subacius, Haris Shalaby, Alaa Schaechter, Andi Levine, Joseph Goldberger, Jeffrey J. CA DEFINITE Investigators TI Significance of follow-up left ventricular ejection fraction measurements in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation trial (DEFINITE) SO HEART RHYTHM LA English DT Article DE Nonischemic cardiomyopathy; Implantable cardioverter-defibrillator; Sudden cardiac death ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SUDDEN CARDIAC DEATH; DILATED CARDIOMYOPATHY; HEART-FAILURE; RISK STRATIFICATION; VARIABILITY; OUTCOMES AB BACKGROUND As left ventricular ejection fraction (LVEF) may improve, worsen, or remain the same over time, patients' prognosis may also be expected to change because of the change in LVEF, among other factors. OBJECTIVE To evaluate the effect of LVEF change on outcome in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial. METHODS Patients with nonischemic cardiomyopathy with LVEF<36%, history of symptomatic heart failure, and the presence of significant ventricular ectopic activity were enrolled in the DEFINITE trial. Follow-up LVEF measurements were obtained annually in only a minority (17%) of trial participants. This study therefore evaluated survival and arrhythmic end points in patients whose LVEF was reassessed between 90 and 730 days after enrollment. RESULTS During the 90-730-day postrandomization period, 187 of 449 (42%) enrolled patients who survived at least 90 days had at least 1 follow-up LVEF measurement; these patients were younger and white; had diabetes, better 6-minute walk test results, and higher BMI; were more likely to have appropriate shocks; and had fewer deaths compared to those without follow-up LVEF measurements. Patients whose LVEF improved had reduced mortality compared to patients whose LVEF decreased (hazard ratio 0.09; 95% confidence interval 0.02-0.39; P = .001). Survival free of appropriate shocks was not significantly related to LVEF improvement during follow-up. CONCLUSIONS LVEF improvement was associated with improved survival, but not with a significant decrease in appropriate shocks. These data highlight that appropriate caution should be exercised not to extrapolate the positive effect of improved LVEF to the elimination of arrhythmic events. C1 [Schliamser, Jorge E.; Kadish, Alan H.; Subacius, Haris; Schaechter, Andi; Goldberger, Jeffrey J.] Northwestern Univ, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Schliamser, Jorge E.; Kadish, Alan H.; Subacius, Haris; Schaechter, Andi; Goldberger, Jeffrey J.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. [Kadish, Alan H.] Touro Coll, Brooklyn, NY USA. [Kadish, Alan H.] New York Med Coll, Valhalla, NY 10595 USA. [Shalaby, Alaa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Levine, Joseph] St Francis Hosp, Ctr Heart, Roslyn, NY USA. RP Goldberger, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, 251 E Huron St,Feinberg 8-503, Chicago, IL 60611 USA. EM j-goldberger@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220 FU St Jude Medical; Sylmar; Medtronic; Boston Scientific; Biotronik FX DEFINITE was funded by St Jude Medical, Sylmar, CA. Dr Kadish is a consultant for Impulse Dynamics and Backbeat Medical AK. Dr Shalaby has received significant research support from St Jude Medical. Dr Levine is an ad hoc consultant for St Jude Medical and Medtronic. Dr Goldberger is Director of the Path to Improved Risk Stratification, NFP, a not-for-profit think tank on the risk stratification for the prevention of sudden cardiac death, which has received unrestricted educational grants from Medtronic, Boston Scientific, and St Jude Medical. He has received grant support and/or honoraria from Medtronic, Biotronik, and St Jude Medical. NR 19 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUN PY 2013 VL 10 IS 6 BP 838 EP 846 DI 10.1016/j.hrthm.2013.02.017 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 152BJ UT WOS:000319504200017 PM 23422221 ER PT J AU Chan, AC Lam, EY Srinivasan, VJ AF Chan, Aaron C. Lam, Edmund Y. Srinivasan, Vivek J. TI Comparison of Kasai Autocorrelation and Maximum Likelihood Estimators for Doppler Optical Coherence Tomography SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Cramer-Rao bound (CRB); Doppler optical coherence tomography; Doppler ultrasound; frequency estimation; maximum likelihood estimation (MLE) ID BLOOD-FLOW; FREQUENCY ESTIMATOR; MEAN FREQUENCY; HIGH-SPEED; VELOCITY; ULTRASOUND; RESOLUTION; FILTER AB In optical coherence tomography (OCT) and ultrasound, unbiased Doppler frequency estimators with low variance are desirable for blood velocity estimation. Hardware improvements in OCT mean that ever higher acquisition rates are possible, which should also, in principle, improve estimation performance. Paradoxically, however, the widely used Kasai autocorrelation estimator's performance worsens with increasing acquisition rate. We propose that parametric estimators based on accurate models of noise statistics can offer better performance. We derive a maximum likelihood estimator (MLE) based on a simple additive white Gaussian noise model, and show that it can outperform the Kasai autocorrelation estimator. In addition, we also derive the Cramer Rao lower bound (CRLB), and show that the variance of the MLE approaches the CRLB for moderate data lengths and noise levels. We note that the MLE performance improves with longer acquisition time, and remains constant or improves with higher acquisition rates. These qualities may make it a preferred technique as OCT imaging speed continues to improve. Finally, our work motivates the development of more general parametric estimators based on statistical models of decorrelation noise. C1 [Chan, Aaron C.; Lam, Edmund Y.] Univ Hong Kong, Dept Elect & Elect Engn, Pokfulam, Hong Kong, Peoples R China. [Srinivasan, Vivek J.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Srinivasan, Vivek J.] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Lam, EY (reprint author), Univ Hong Kong, Dept Elect & Elect Engn, Pokfulam, Pokfulam, Hong Kong, Peoples R China. EM cwachan@eee.hku.hk; elam@eee.hku.hk; vjsriniv@ucdavis.edu FU University Research Committee of the University of Hong Kong [10401797]; National Institutes of Health [R00NS067050, EB001954 R01]; American Heart Association [11IRG5440002]; Glaucoma Research Foundation Catalyst for a Cure FX This work was supported in part by the University Research Committee of the University of Hong Kong under Project 10401797, in part by in part by the National Institutes of Health (R00NS067050, EB001954 R01), in part by the American Heart Association (11IRG5440002), and in part by the Glaucoma Research Foundation Catalyst for a Cure. NR 36 TC 8 Z9 8 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 2013 VL 32 IS 6 BP 1033 EP 1042 DI 10.1109/TMI.2013.2248163 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 154UQ UT WOS:000319701800006 PM 23446044 ER PT J AU Valenza, G Citi, L Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Scilingo, Enzo Pasquale Barbieri, Riccardo TI Point-Process Nonlinear Models With Laguerre and Volterra Expansions: Instantaneous Assessment of Heartbeat Dynamics SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE Bispectrum; heart rate variability (HRV); high order statistics; Laguerre expansion; nonlinear analysis; point process; trispectrum; Wiener-Volterra model ID HIGHER-ORDER SPECTRA; TIME-SERIES ANALYSIS; RATE-VARIABILITY; SYSTEM-IDENTIFICATION; CARDIOVASCULAR VARIABILITY; AUTONOMIC MODULATION; APPROXIMATE ENTROPY; STATISTICAL-METHODS; PERIOD VARIABILITY; GAUSSIAN INPUTS AB In the last decades, mathematical modeling and signal processing techniques have played an important role in the study of cardiovascular control physiology and heartbeat nonlinear dynamics. In particular, nonlinear models have been devised for the assessment of the cardiovascular system by accounting for short-memory second-order nonlinearities. In this paper, we introduce a novel inverse Gaussian point process model with Laguerre expansion of the nonlinear Volterra kernels. Within the model, the second-order nonlinearities also account for the long-term information given by the past events of the nonstationary non-Gaussian time series. In addition, the mathematical link to an equivalent cubic input-output Wiener-Volterra model allows for a novel instantaneous estimation of the dynamic spectrum, bispectrum and trispectrum of the considered inter-event intervals. The proposed framework is tested with synthetic simulations and two experimental heartbeat interval datasets. Applications on further heterogeneous datasets such as milling inserts, neural spikes, gait from short walks, and geyser geologic events are also reported. Results show that our model improves on previously developed models and, at the same time, it is able to provide a novel instantaneous characterization and tracking of the inherent nonlinearity of heartbeat dynamics. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA. [Valenza, Gaetano; Scilingo, Enzo Pasquale] Univ Pisa, Dept Informat Engn, I-56126 Pisa, Italy. [Valenza, Gaetano; Scilingo, Enzo Pasquale] Univ Pisa, Res Ctr E Piaggio, I-56126 Pisa, Italy. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@ieee.org; e.scilingo@centropiaggio.unipi.it; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Scilingo, Enzo Pasquale/0000-0003-2588-4917; Valenza, Gaetano/0000-0001-6574-1879 FU NIH [R01-HL0845 02]; EU Commission [ICT-247777 Psyche] FX This work was supported in part by the NIH Grant R01-HL0845 02 and by the EU Commission under contract ICT-247777 Psyche. NR 89 TC 25 Z9 25 U1 0 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-587X EI 1941-0476 J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD JUN PY 2013 VL 61 IS 11 BP 2914 EP 2926 DI 10.1109/TSP.2013.2253775 PG 13 WC Engineering, Electrical & Electronic SC Engineering GA 153HQ UT WOS:000319592700015 ER PT J AU Brody, AL Mukhin, AG La Charite, J Ta, K Farahi, J Sugar, CA Mamoun, MS Vellios, E Archie, M Kozman, M Phuong, J Arlorio, F Mandelkern, MA AF Brody, Arthur L. Mukhin, Alexey G. La Charite, Jaime Ta, Karen Farahi, Judah Sugar, Catherine A. Mamoun, Michael S. Vellios, Evan Archie, Meena Kozman, Maggie Phuong, Jonathan Arlorio, Franca Mandelkern, Mark A. TI Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Age; nicotine dependence; nicotinic acetylcholine receptor; positron emission tomography; tobacco ID SMOKING-CESSATION; TOBACCO SMOKING; HUMAN-BRAIN; AFRICAN-AMERICAN; UNITED-STATES; YOUNG-ADULTS; BINDING; ABSTINENCE; OCCUPANCY; PET AB One-third of smokers primarily use menthol cigarettes and usage of these cigarettes leads to elevated serum nicotine levels and more difficulty quitting in standard treatment programmes. Previous brain imaging studies demonstrate that smoking (without regard to cigarette type) leads to up-regulation of beta*(2)-containing nicotinic acetylcholine receptors (nAChRs). We sought to determine if menthol cigarette usage results in greater nAChR up-regulation than non-menthol cigarette usage. Altogether, 114 participants (22 menthol cigarette smokers, 41 non-menthol cigarette smokers and 51 non-smokers) underwent positron emission tomography scanning using the alpha(4)beta*(2) nAChR radioligand 2-[F-18]fluoro-A-85380 (2-FA). In comparing menthol to non-menthol cigarette smokers, an overall test of 2-FA total volume of distribution values revealed a significant between-group difference, resulting from menthol smokers having 9-28% higher alpha(4)beta*(2) nAChR densities than non-menthol smokers across regions. In comparing the entire group of smokers to non-smokers, an overall test revealed a significant between-group difference, resulting from smokers having higher alpha(4)beta*(2) nAChR levels in all regions studied (36-42%) other than thalamus (3%). Study results demonstrate that menthol smokers have greater up-regulation of nAChRs than non-menthol smokers. This difference is presumably related to higher nicotine exposure in menthol smokers, although other mechanisms for menthol influencing receptor density are possible. These results provide additional information about the severity of menthol cigarette use and may help explain why these smokers have more trouble quitting in standard treatment programmes. C1 [Brody, Arthur L.; Sugar, Catherine A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Brody, Arthur L.; La Charite, Jaime; Ta, Karen; Mamoun, Michael S.; Vellios, Evan; Archie, Meena; Kozman, Maggie; Phuong, Jonathan; Arlorio, Franca; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA. [Mukhin, Alexey G.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Farahi, Judah] VA Greater Los Angeles Healthcare Syst, Dept Radiochem, Los Angeles, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU Tobacco-Related Disease Research Program [19XT-0135]; National Institute on Drug Abuse [R01 DA20872]; Veterans Affairs Type I Merit Review Award; Richard Metzner Chair in Clinical Neuropharmacology; Pfizer, Inc.; Phillip Morris, Inc. FX This study was supported by the Tobacco-Related Disease Research Program [A.L.B. (19XT-0135)], the National Institute on Drug Abuse [A.L.B. (R01 DA20872)] and a Veterans Affairs Type I Merit Review Award (A.L.B.), as well as by an endowment from the Richard Metzner Chair in Clinical Neuropharmacology (A.L.B.). The sponsors had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data or preparation, review or approval of the manuscript.; Drs Brody and Mandelkern were previously co-investigators on a grant funded by Pfizer, Inc., which was unrelated to this study. Dr Mukhin is a co-investigator on a grant from Phillip Morris, Inc., for research unrelated to this study. NR 57 TC 18 Z9 19 U1 0 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2013 VL 16 IS 5 BP 957 EP 966 DI 10.1017/S1461145712001022 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 146WW UT WOS:000319127100003 PM 23171716 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI The Red Journal's Most Downloaded Articles of 2012 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID CLINICAL TARGET VOLUME; MODULATED PELVIC RADIOTHERAPY; ADVANCED PANCREATIC-CANCER; TERM-FOLLOW-UP; RADIATION-THERAPY; BRACHIAL-PLEXUS; BREAST-CANCER; POSTMASTECTOMY RADIATION; POSTOPERATIVE TREATMENT; CONSENSUS GUIDELINES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 35 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2013 VL 86 IS 2 BP 218 EP 221 DI 10.1016/j.ijrobp.2013.03.011 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 151ZZ UT WOS:000319500200009 PM 23643376 ER PT J AU Bahig, H Roberge, D Bosch, W Levin, W Petersen, I Haddock, M Freeman, C DeLaney, TF Abrams, RA Indelicato, DJ Baldini, EH Hitchcock, Y Kirsch, DG Kozak, KR Wolfson, A Wang, D AF Bahig, Houda Roberge, David Bosch, Walter Levin, William Petersen, Ivy Haddock, Michael Freeman, Carolyn DeLaney, Thomas F. Abrams, Ross A. Indelicato, Danny J. Baldini, Elizabeth H. Hitchcock, Ying Kirsch, David G. Kozak, Kevin R. Wolfson, Aaron Wang, Dian TI Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID POSTOPERATIVE RADIOTHERAPY; TUMORS; CONSENSUS; IMAGES AB Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV) 3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm 3 (7413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm 3 (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa Z 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. (C) 2013 Elsevier Inc. C1 [Bahig, Houda; Roberge, David; Indelicato, Danny J.] Ctr Hosp Univ Montreal, Dept Radiat Oncol, Montreal, PQ, Canada. [Bosch, Walter] Washington Univ, Dept Radiat Oncol, St Louis, MO USA. [Levin, William] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Petersen, Ivy; Haddock, Michael] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Freeman, Carolyn] McGill Univ, Ctr Hlth, Div Radiat Oncol, Montreal, PQ, Canada. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Abrams, Ross A.] Rush Univ, Dept Radiat Oncol, Med Ctr, Chicago, IL 60612 USA. [Indelicato, Danny J.] Univ Florida, Med Ctr, Dept Radiat Oncol, Jacksonville, FL 32209 USA. [Baldini, Elizabeth H.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hitchcock, Ying] Univ Utah, Med Ctr, Dept Radiat Oncol, Salt Lake City, UT USA. [Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Kozak, Kevin R.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI USA. [Wolfson, Aaron] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA. [Wang, Dian] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. RP Roberge, D (reprint author), Hop Notre Came, Radiat Oncol, TS-3366,1560 Sherbrooke Est, Montreal, PQ H2L 4M1, Canada. EM david.roberge.chum@ssss.gouv.qc.ca OI Indelicato, Daniel/0000-0001-5765-1873 FU National Cancer Institute (NCI) [U10 CA37422] FX Community Clinical Oncology Program (CCOP) grant U10 CA37422 from the National Cancer Institute (NCI). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NCI. NR 16 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2013 VL 86 IS 2 BP 298 EP 303 DI 10.1016/j.ijrobp.2013.01.032 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 151ZZ UT WOS:000319500200021 PM 23474110 ER PT J AU Coen, JJ Paly, JJ Niemierko, A Kaufman, DS Heney, NM Spiegel, DY Efstathiou, JA Zietman, AL Shipley, WU AF Coen, John J. Paly, Jonathan J. Niemierko, Andrzej Kaufman, Donald S. Heney, Niall M. Spiegel, Daphne Y. Efstathiou, Jason A. Zietman, Anthony L. Shipley, William U. TI Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID PROSTATE-CANCER; RADICAL CYSTECTOMY; SELECTIVE BLADDER; RECURRENCE; RADIATION; RISK; PRESERVATION; CHEMOTHERAPY; RADIOTHERAPY; PROBABILITY AB Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BIDFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions. (C) 2013 Elsevier Inc. C1 [Coen, John J.; Paly, Jonathan J.; Niemierko, Andrzej; Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kaufman, Donald S.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Heney, Niall M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Coen, JJ (reprint author), Hartford Hosp, Helen & Harry Gray Canc Ctr, Dept Radiat Oncol, 80 Seymour St, Hartford, CT 06102 USA. EM jcoen@harthosp.org NR 21 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2013 VL 86 IS 2 BP 311 EP 316 DI 10.1016/j.ijrobp.2013.01.020 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 151ZZ UT WOS:000319500200023 PM 23474117 ER PT J AU Grassberger, C Dowdell, S Lomax, A Sharp, G Shackleford, J Choi, N Willers, H Paganetti, H AF Grassberger, Clemens Dowdell, Stephen Lomax, Antony Sharp, Greg Shackleford, James Choi, Noah Willers, Henning Paganetti, Harald TI Motion Interplay as a Function of Patient Parameters and Spot Size in Spot Scanning Proton Therapy for Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADIOTHERAPY; TARGETS; VOLUME; BEAM AB Purpose: To quantify the impact of respiratory motion on the treatment of lung tumors with spot scanning proton therapy. Methods and Materials: Four-dimensional Monte Carlo simulations were used to assess the interplay effect, which results from relative motion of the tumor and the proton beam, on the dose distribution in the patient. Ten patients with varying tumor sizes (2.6-82.3 cc) and motion amplitudes (3-30 mm) were included in the study. We investigated the impact of the spot size, which varies between proton facilities, and studied single fractions and conventionally fractionated treatments. The following metrics were used in the analysis: minimum/maximum/mean dose, target dose homogeneity, and 2-year local control rate (2y-LC). Results: Respiratory motion reduces the target dose homogeneity, with the largest effects observed for the highest motion amplitudes. Smaller spot sizes (sigma approximate to 3 mm) are inherently more sensitive to motion, decreasing target dose homogeneity on average by a factor 2.8 compared with a larger spot size (sigma approximate to 13 mm). Using a smaller spot size to treat a tumor with 30-mm motion amplitude reduces the minimum dose to 44.7% of the prescribed dose, decreasing modeled 2y-LC from 87.0% to 2.7%, assuming a single fraction. Conventional fractionation partly mitigates this reduction, yielding a 2y-LC of 71.6%. For the large spot size, conventional fractionation increases target dose homogeneity and prevents a deterioration of 2y-LC for all patients. No correlation with tumor volume is observed. The effect on the normal lung dose distribution is minimal: observed changes in mean lung dose and lung V-20 are <0.6 Gy(RBE) and <1.7%, respectively. Conclusions: For the patients in this study, 2y-LC could be preserved in the presence of interplay using a large spot size and conventional fractionation. For treatments using smaller spot sizes and/or in the delivery of single fractions, interplay effects can lead to significant deterioration of the dose distribution and lower 2y-LC. (C) 2013 Elsevier Inc. C1 [Grassberger, Clemens; Dowdell, Stephen; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grassberger, Clemens; Dowdell, Stephen; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Grassberger, Clemens; Lomax, Antony] Paul Scherrer Inst, Ctr Proton Radiotherapy, Villigen, Switzerland. RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM Grassberger.Clemens@mgh.harvard.edu OI Shackleford, James/0000-0002-7987-651X FU National Cancer Institute [R01 CA111590] FX This project was supported by the National Cancer Institute Grant No. R01 CA111590. We thank Ben Clasie, Antje Knopf, and Joost Verburg for their assistance. NR 15 TC 35 Z9 35 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2013 VL 86 IS 2 BP 380 EP 386 DI 10.1016/j.ijrobp.2013.01.024 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 151ZZ UT WOS:000319500200033 PM 23462423 ER PT J AU Geng, EH Bwana, MB Muyindike, W Glidden, DV Bangsberg, DR Neilands, TB Bernheimer, I Musinguzi, N Yiannoutsos, CT Martin, JN AF Geng, Elvin H. Bwana, Mwebesa B. Muyindike, Winnie Glidden, David V. Bangsberg, David R. Neilands, Torsten B. Bernheimer, Ingrid Musinguzi, Nicolas Yiannoutsos, Constantin T. Martin, Jeffrey N. TI Failure to Initiate Antiretroviral Therapy, Loss to Follow-up and Mortality Among HIV-Infected Patients During the Pre-ART Period in Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; Africa; loss to follow-up; mortality ID SAMPLING-BASED APPROACH; FOOD INSECURITY; COMPETING RISKS; SOUTH-AFRICA; TUBERCULOSIS; PROGRAMS; OUTCOMES; CARE; ACCEPTANCE; COUNTRIES AB Background: Delays and failures in initiation of antiretroviral therapy (ART) among treatment eligible patients may compromise the effectiveness of HIV care in Africa. An accurate understanding, however, of the pace and completeness of ART initiation and mortality during the waiting period is obscured by frequent losses to follow-up. Methods: We evaluated newly ART-eligible HIV-infected adults from 2007 to 2011 in a prototypical clinic in Mbarara, Uganda. A random sample of patients lost to follow-up was tracked in the community to determine vital status and ART initiation after leaving the original clinic. Outcomes among the tracked patients were incorporated using probability weights, and a competing risks approach was used in analyses. Results: Among 2633 ART-eligible patients, 490 were lost to follow-up, of whom a random sample of 132 was tracked and 111 (84.0%) had outcomes ascertained. After incorporating the outcomes among the lost, the cumulative incidence of ART initiation at 30, 90, and 365 days after eligibility was 16.0% [ 95% confidence interval (CI): 14.2 to 17.7], 64.5% (95% CI: 60.9 to 68.1), and 81.7% (95% CI: 77.7 to 85.6). Death before ART was 7.7% at 1 year. Male sex, higher CD4 count, and no education were associated with delayed ART initiation. Lower CD4 level, malnourishment, and travel time to clinic were associated with mortality. Conclusions: Using a sampling-based approach to account for losses to follow-up revealed that both the speed and the completeness of ART initiation were suboptimal in a prototypical large clinic in Uganda. Improving the kinetics of ART initiation in Africa is needed to make ART more in real-world populations. C1 [Geng, Elvin H.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div HIV AIDS, San Francisco, CA 94110 USA. [Geng, Elvin H.; Bwana, Mwebesa B.; Muyindike, Winnie; Glidden, David V.; Bangsberg, David R.; Musinguzi, Nicolas; Yiannoutsos, Constantin T.; Martin, Jeffrey N.] East Africa Int Epidemiol Databases Evaluate AIDS, Indianapolis, IN USA. [Bwana, Mwebesa B.; Muyindike, Winnie; Bangsberg, David R.; Musinguzi, Nicolas] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Glidden, David V.; Bernheimer, Ingrid; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Neilands, Torsten B.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA 94110 USA. [Yiannoutsos, Constantin T.] Indiana Univ, Dept Biostat, Indianapolis, IN 46204 USA. RP Geng, EH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, 995 Potrero Ave,Bldg 80, San Francisco, CA 94110 USA. EM genge@php.ucsf.edu FU National Institutes of Health [K23 AI084544, U01 AI069911, P30 AI027763]; United States President's Emergency Plan for AIDS Relief FX Supported by the National Institutes of Health Grants K23 AI084544, U01 AI069911, and P30 AI027763; the United States President's Emergency Plan for AIDS Relief. NR 32 TC 34 Z9 34 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2013 VL 63 IS 2 BP E64 EP E71 DI 10.1097/QAI.0b013e31828af5a6 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 146SY UT WOS:000319112500004 PM 23429504 ER PT J AU Joshi, G Wozniak, J Petty, C Martelon, MK Fried, R Bolfek, A Kotte, A Stevens, J Furtak, SL Bourgeois, M Caruso, J Caron, A Biederman, J AF Joshi, Gagan Wozniak, Janet Petty, Carter Martelon, Mary Kate Fried, Ronna Bolfek, Anela Kotte, Amelia Stevens, Jonathan Furtak, Stephannie L. Bourgeois, Michelle Caruso, Janet Caron, Ashley Biederman, Joseph TI Psychiatric Comorbidity and Functioning in a Clinically Referred Population of Adults with Autism Spectrum Disorders: A Comparative Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Psychiatric comorbidity; Adults ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; ASPERGER-SYNDROME; YOUNG-ADULTS; INTELLECTUAL DISABILITY; RESONANCE SPECTROSCOPY; BIPOLAR DISORDER; ANXIETY SYMPTOMS; AMYGDALA VOLUME AB To systematically examine the patterns of psychiatric comorbidity and functioning in clinically referred adults with autism spectrum disorders (ASD). Psychiatrically referred adults with and without ASD were compared on measures assessing for psychiatric comorbidity and psychosocial functioning. Sixty-three adults with ASD participated in the study (mean age: 29 +/- A 11 years). Adults with ASD in their lifetime suffered from a higher burden of psychiatric disorders (6 +/- A 3.4 vs. 3.5 +/- A 2.7; p < 0.001) including major depressive disorder and multiple anxiety disorders, and were functionally more impaired with a significant proportion having received both counseling and pharmacotherapy. Adults with ASD have high levels of psychiatric comorbidity and dysfunction comparable to a clinically referred population of adults without ASD. C1 [Joshi, Gagan; Wozniak, Janet; Petty, Carter; Martelon, Mary Kate; Fried, Ronna; Bolfek, Anela; Kotte, Amelia; Stevens, Jonathan; Furtak, Stephannie L.; Bourgeois, Michelle; Caruso, Janet; Caron, Ashley; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Joshi, Gagan; Wozniak, Janet; Fried, Ronna; Bolfek, Anela; Kotte, Amelia; Stevens, Jonathan; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM joshi.gagan@mgh.harvard.edu OI Kotte, Amelia/0000-0002-0198-7914 NR 65 TC 47 Z9 47 U1 8 U2 38 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2013 VL 43 IS 6 BP 1314 EP 1325 DI 10.1007/s10803-012-1679-5 PG 12 WC Psychology, Developmental SC Psychology GA 154NJ UT WOS:000319682400007 PM 23076506 ER PT J AU Waslawski, S Lo, ES Ewing, SA Young, VB Aronoff, DM Sharp, SE Novak-Weekley, SM Crist, AE Dunne, WM Hoppe-Bauer, J Johnson, M Brecher, SM Newton, DW Walk, ST AF Waslawski, Sheila Lo, Eugene S. Ewing, Sarah A. Young, Vincent B. Aronoff, David M. Sharp, Susan E. Novak-Weekley, Susan M. Crist, Arthur E., Jr. Dunne, W. Michael Hoppe-Bauer, Joan Johnson, Michelle Brecher, Stephen M. Newton, Duane W. Walk, Seth T. TI Clostridium difficile Ribotype Diversity at Six Health Care Institutions in the United States SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID EPIDEMIOLOGY; INFECTION AB Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart. C1 [Waslawski, Sheila; Lo, Eugene S.; Ewing, Sarah A.; Young, Vincent B.; Aronoff, David M.; Walk, Seth T.] Univ Michigan Hosp & Hlth Syst, Div Infect Dis, Dept Internal Med, Ann Arbor, MI USA. [Young, Vincent B.; Aronoff, David M.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Sharp, Susan E.] Kaiser Permanente NW, Portland, OR USA. [Novak-Weekley, Susan M.] So Calif Permanente Med Grp, Reg Reference Labs, North Hollywood, CA USA. [Crist, Arthur E., Jr.] York Hosp, Dept Lab Serv, Div Clin Microbiol, York, PA USA. [Dunne, W. Michael] BioMerieux, Durham, NC USA. [Dunne, W. Michael; Hoppe-Bauer, Joan; Johnson, Michelle] Barnes Jewish Hosp, Dept Microbiol, St Louis, MO 63110 USA. [Brecher, Stephen M.] VA Boston Healthcare Syst, Boston, MA USA. [Newton, Duane W.] Univ Michigan Hosp & Hlth Syst, Dept Pathol, Clin Microbiol Labs, Ann Arbor, MI USA. [Walk, Seth T.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. RP Walk, ST (reprint author), Univ Michigan Hosp & Hlth Syst, Div Infect Dis, Dept Internal Med, Ann Arbor, MI USA. EM seth.walk@montana.edu FU Department of Pathology at the University of Michigan; National Institutes of Health [1U19AI090871-01, 1K01AI09728101A1] FX This work was supported by institutional funds from the Department of Pathology at the University of Michigan. Additional support came from the National Institutes of Health grants 1U19AI090871-01 (to V.B.Y. and D.M.A.) and 1K01AI09728101A1 (to S.T.W.). NR 15 TC 13 Z9 14 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2013 VL 51 IS 6 BP 1938 EP 1941 DI 10.1128/JCM.00056-13 PG 4 WC Microbiology SC Microbiology GA 147VV UT WOS:000319197800047 PM 23554188 ER PT J AU Nair, BG Horibe, M Newman, SF Wu, WY Schwid, HA AF Nair, Bala G. Horibe, Mayumi Newman, Shu-Fang Wu, Wei-Ying Schwid, Howard A. TI Near real-time notification of gaps in cuff blood pressure recordings for improved patient monitoring SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE Decision support; Anesthesia information management system; Patient monitoring; Blood pressure monitoring; Real-time reminders ID DOCUMENTATION; PERFORMANCE; QUALITY AB Blood pressure monitoring during anesthesia is an American Society of Anesthesiology standard. However, the anesthesia provider sometimes fails to engage the patient monitor to make periodic (generally every 3-5 min) measurements of Non-Invasive Blood Pressure (NIBP), which can lead to extended periods (> 5 min) when blood pressure is not monitored. We describe a system to automatically detect such gaps in NIBP measurement and notify clinicians in real-time to initiate measurement. We applied a decision support system called the Smart Anesthesia Messenger (SAM) to notify the anesthesia provider if NIBP measurements have not been made in the last 7 min. Notification messages were generated only if direct arterial blood pressure was not being monitored. NIBP gaps were analyzed for 9 months before and after SAM notification was initiated (12,000 cases for each period). SAM notification was able to reduce the occurrence of extended NIBP gaps > 15 min from 15.7 +/- A 4.5 to 6.7 +/- A 2.0 instances per 1,000 cases (p < 0.001). In addition, for extended gaps (> 15 min) the mean gap duration declined from 23.1 +/- A 2.0 to 18.6 +/- A 1.1 min after SAM notification was initiated (p < 0.001). However, for 7-15 min gaps, SAM notification was not effective in reducing the occurrence. The maximum gap encountered before SAM was 64 min, while it was 27 min with SAM notification. Real-time notification using SAM is an effective way to reduce both the number of instances and the duration of inadvertent, extended (> 15 min) gaps in blood pressure measurements in the operating room. However, the frequency of gaps < 15 min could not be reduced using the current configuration of SAM. C1 [Nair, Bala G.; Schwid, Howard A.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Horibe, Mayumi] VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA USA. [Newman, Shu-Fang] Univ Washington, Patient Care Serv, Seattle, WA 98195 USA. [Wu, Wei-Ying] Natl Dong Hwa Univ, Dept Appl Math, Hualien, Taiwan. RP Nair, BG (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, BB-1469 Hlth Sci Bldg,1959 NE Pacific St,Mail Box, Seattle, WA 98195 USA. EM nairbg@uw.edu FU Laura Cheney Patient Safety grant by the University of Washington FX This research was supported by Laura Cheney Patient Safety grant provided by the University of Washington. We would also like to thank Rafael Vergara for his daily support of the SAM system. NR 15 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1387-1307 J9 J CLIN MONIT COMPUT JI J. Clin. Monitor. Comp. PD JUN PY 2013 VL 27 IS 3 BP 265 EP 271 DI 10.1007/s10877-012-9425-2 PG 7 WC Anesthesiology SC Anesthesiology GA 146DW UT WOS:000319070600009 PM 23283561 ER PT J AU Pirl, WF Jacobsen, PB Deshields, TL AF Pirl, William F. Jacobsen, Paul B. Deshields, Teresa L. TI Opportunities for Improving Psychosocial Care for Cancer Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RANDOMIZED-TRIAL; BREAST-CANCER; DEPRESSION; MANAGEMENT; ONCOLOGISTS; NEEDS C1 [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Deshields, Teresa L.] Siteman Canc Ctr, Siteman Counseling Serv, St Louis, MO USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2013 VL 31 IS 16 BP 1920 EP 1921 DI 10.1200/JCO.2012.48.0566 PG 2 WC Oncology SC Oncology GA 154FP UT WOS:000319657600009 PM 23610106 ER PT J AU Metzger, O Procter, M de Azambuja, E Leyland-Jones, B Gelber, RD Dowsett, M Loi, S Saini, KS Cameron, D Untch, M Smith, I Gianni, L Baselga, J Jackisch, C Bell, R Sotiriou, C Viale, G Piccart-Gebhart, M AF Metzger-Filho, Otto Procter, Marion de Azambuja, Evandro Leyland-Jones, Brian Gelber, Richard D. Dowsett, Mitchell Loi, Sherene Saini, Kamal S. Cameron, David Untch, Michael Smith, Ian Gianni, Luca Baselga, Jose Jackisch, Christian Bell, Richard Sotiriou, Christos Viale, Giuseppe Piccart-Gebhart, Martine TI Magnitude of Trastuzumab Benefit in Patients With HER2-Positive, Invasive Lobular Breast Carcinoma: Results From the HERA Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT CHEMOTHERAPY; PROGNOSTIC VALUE; CANCER; AMPLIFICATION; EXPRESSION; IMMUNOHISTOCHEMISTRY; OVEREXPRESSION; ASSOCIATION; RECEPTORS; ESTROGEN AB Purpose To evaluate the benefit of adjuvant trastuzumab in patients diagnosed with human epidermal growth factor receptor 2 (HER2) -positive invasive lobular carcinoma (ILC) enrolled onto the Herceptin Adjuvant (HERA) trial. Patients and Methods Patients randomly assigned to receive one year of trastuzumab and one year of observation in the HERA trial were included (n = 3,401). Centrally reviewed estrogen receptor (ER), progesterone receptor (PgR), and HER2 copy numbers were used. First site-specific relapse pattern was evaluated for ILC and invasive ductal carcinoma (IDC). The magnitude of trastuzumab benefit was assessed using the Cox proportional hazards model for disease-free survival (DFS) and overall survival (OS). Results Median follow-up time was 4 years. A total of 187 ILC and 3,213 IDC patients were included. High Allred scores (6 to 8) were more common in patients with ILC than IDC for both ER (36.9% v 22.7%) and PgR (44.1% v 28.5%). A trend toward decreased HER2 copy number was observed in the ILC group. The ILC and IDC subgroups had similar patterns of first site of disease relapse. DFS hazard ratios (HRs) comparing 1 year of trastuzumab versus observation were 0.63 for ILC (95% CI, 0.34 to 1.15) and 0.77 for IDC (95% CI, 0.67 to 0.89; P for interaction = .49). The OS HRs comparing 1 year of trastuzumab versus observation were 0.60 for ILC (95% CI, 0.27 to 1.31) and 0.86 for IDC (95% CI, 0.71 to 1.06; P for interaction = .29). Conclusion In this retrospective analysis, there was no suggestion that patients in the ILC cohort experienced a different magnitude of benefit from adjuvant trastuzumab than those in the IDC cohort. (c) 2013 by American Society of Clinical Oncology C1 [Metzger-Filho, Otto] Harvard Univ, Sch Med, Dana Farber Canc Inst, Sch Publ Hlth, Boston, MA 02115 USA. [Metzger-Filho, Otto; de Azambuja, Evandro; Saini, Kamal S.; Sotiriou, Christos; Piccart-Gebhart, Martine] Inst Jules Bordet, B-1000 Brussels, Belgium. [Metzger-Filho, Otto; de Azambuja, Evandro; Saini, Kamal S.; Sotiriou, Christos; Piccart-Gebhart, Martine] Univ Libre Brussels, Brussels, Belgium. [Procter, Marion] Frontier Sci Scotland, Kincraig, Scotland. [Dowsett, Mitchell; Smith, Ian] Royal Marsden Hosp, London, England. [Smith, Ian] Inst Canc Res, London, England. [Cameron, David] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Leyland-Jones, Brian] Edith Sanford Breast Res, Sioux Falls, SD USA. [Loi, Sherene] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Bell, Richard] Andrew Love Canc Ctr, Geelong, Vic, Australia. [Untch, Michael] HELIOS Klin, Berlin, Germany. [Jackisch, Christian] Klinikum Offenbach, Offenbach, Germany. [Gianni, Luca] San Raffaele Inst, Milan, Italy. [Viale, Giuseppe] European Inst Oncol, Milan, Italy. [Viale, Giuseppe] Univ Milan, Milan, Italy. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Piccart-Gebhart, M (reprint author), Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium. EM martine.piccart@bordet.be RI Loi, Sherene/H-1979-2016; OI Loi, Sherene/0000-0001-6137-9171 FU Roche FX Marion Procter, Roche; Richard D. Gelber, Roche; Mitchell Dowsett, Roche; David Cameron, Roche NR 27 TC 9 Z9 11 U1 0 U2 5 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 JUN 1 PY 2013 VL 31 IS 16 BP 1954 EP U254 DI 10.1200/JCO.2012.46.2440 PG 8 WC Oncology SC Oncology GA 154FP UT WOS:000319657600015 PM 23589556 ER PT J AU Warren, JL Harlan, LC Stevens, J Little, RF Abel, GA AF Warren, Joan L. Harlan, Linda C. Stevens, Jennifer Little, Richard F. Abel, Gregory A. TI Multiple Myeloma Treatment Transformed: A Population-Based Study of Changes in Initial Management Approaches in the United States SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; STANDARD CHEMOTHERAPY; PLUS THALIDOMIDE; ELDERLY-PATIENTS; SURVIVAL; TRIAL; PREDNISONE; MELPHALAN; DEXAMETHASONE AB Purpose Despite improved outcomes for multiple myeloma, little is known about changes in initial treatment at the population level for US patients. We report trends in treatment practices. Patients and Methods Patients (n = 1,976) with newly diagnosed myeloma in 1999, 2003, and 2007 were examined by using the National Cancer Institute's Patterns of Care Studies. We assessed use of common chemotherapies (melphalan, vincristine, and doxorubicin), novel agents (thalidomide, bortezomib, or lenalidomide), or hematopoietic stem-cell transplantation (HSCT) during the first year after diagnosis. By using logistic regression, we evaluated the association of race and insurance status with receipt of high-cost treatments-transplantation or novel agents. Results From 1999 to 2007, use of melphalan alone dropped from 32.0% to 4.1%, and vincristine and doxorubicin use declined from 18.2% to 0.4%. The percentage of patients receiving any novel agent rose from 3.9% in 1999 to 75.5% in 2007. HSCT increased from 11.1% in 1999 to 21.7% in 2007. For white patients, use of novel agents was lower for those with Medicare only (42.6%) than for those with private insurance (50.2%). For patients of other races, those with Medicare only or Medicaid were less likely to receive novel agents or transplantation compared with those with private insurance. Conclusion Initial treatment for multiple myeloma has changed markedly. Most patients now receive novel agents, with a decline in the use of traditional chemotherapy. Use of transplantation and novel agents varies with race and insurance. These findings document rapid changes in patterns of care and highlight addressable disparities in myeloma care. (c) 2013 by American Society of Clinical Oncology C1 [Warren, Joan L.; Harlan, Linda C.; Little, Richard F.] NCI, Bethesda, MD 20892 USA. [Stevens, Jennifer] Informat Management Serv Inc, Silver Spring, MD USA. [Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Warren, JL (reprint author), NCI, 6130 Execut Blvd,Room 4005,MSC 7344, Bethesda, MD 20892 USA. EM joan_warren@nih.gov NR 26 TC 19 Z9 19 U1 2 U2 5 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 JUN 1 PY 2013 VL 31 IS 16 BP 1984 EP + DI 10.1200/JCO.2012.46.3323 PG 7 WC Oncology SC Oncology GA 154FP UT WOS:000319657600019 PM 23569317 ER PT J AU Diamond, JR Salgia, R Varella-Garcia, M Kanteti, R LoRusso, PM Clark, JW Xu, LG Wilner, K Eckhardt, SG Ching, KA Lira, ME Schoenmakers, EFPM Christensen, JG Camidge, DR AF Diamond, Jennifer R. Salgia, Ravi Varella-Garcia, Marileila Kanteti, Rajani LoRusso, Patricia M. Clark, Jeffrey W. Xu, Ling-Guo Wilner, Keith Eckhardt, S. Gail Ching, Keith A. Lira, Maruja E. Schoenmakers, Eric F. P. M. Christensen, James G. Camidge, D. Ross TI Initial Clinical Sensitivity and Acquired Resistance to MET Inhibition in MET-Mutated Papillary Renal Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; ADVANCED SOLID TUMORS; C-MET; SIGNALING PATHWAY; AMG 102; CANCER; MUTATIONS; RECEPTOR; CRIZOTINIB; SURVIVAL C1 [Diamond, Jennifer R.; Varella-Garcia, Marileila; Xu, Ling-Guo; Eckhardt, S. Gail; Camidge, D. Ross] Univ Colorado, Ctr Canc, Aurora, CO USA. [Salgia, Ravi; Kanteti, Rajani] Univ Chicago, Chicago, IL 60637 USA. [LoRusso, Patricia M.] Karmanos Canc Inst, Detroit, MI USA. [Clark, Jeffrey W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilner, Keith; Ching, Keith A.; Lira, Maruja E.; Schoenmakers, Eric F. P. M.; Christensen, James G.] Pfizer, San Diego, CA USA. RP Diamond, JR (reprint author), Univ Colorado, Ctr Canc, Aurora, CO USA. FU National Institutes of Health (NIH)/National Cancer Institute (NCI) [5R01CA100750-06, 5R01CA125541-05, 5K12CA086913-10]; Pfizer FX Supported in part by National Institutes of Health (NIH)/National Cancer Institute (NCI) Grants No. 5R01CA100750-06 (R.S.) and 5R01CA125541-05, and by NIH/NCI Grant No. 5K12CA086913-10 (J.R.D.). We thank Pamela Vizcarra for preparing the tumor slides for analysis.; Patricia M. LoRusso, Pfizer; Jeffrey W. Clark, Pfizer; S. Gail Eckhardt, Pfizer NR 25 TC 7 Z9 7 U1 1 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 JUN 1 PY 2013 VL 31 IS 16 BP E254 EP E258 DI 10.1200/JCO.2012.46.4289 PG 5 WC Oncology SC Oncology GA 154FP UT WOS:000319657600004 PM 23610116 ER PT J AU Meir, JU Milsom, WK AF Meir, Jessica U. Milsom, William K. TI High thermal sensitivity of blood enhances oxygen delivery in the high-flying bar-headed goose SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE blood-oxygen affinity; oxygen-hemoglobin equilibrium curve; temperature effect; CO2 Bohr effect; Anser indicus; high altitude ID HIGH-ALTITUDE; DISSOCIATION CURVE; BIRD BLOOD; RESPIRATORY PROPERTIES; BODY-TEMPERATURE; HEMOGLOBIN; AFFINITY; EQUILIBRIUM; EXERCISE; HYPOXIA AB The bar-headed goose (Anser indicus) crosses the Himalaya twice a year at altitudes where oxygen (O-2) levels are less than half those at sea level and temperatures are below -20 degrees C. Although it has been known for over three decades that the major hemoglobin (Hb) component of bar-headed geese has an increased affinity for O-2, enhancing O-2 uptake, the effects of temperature and interactions between temperature and pH on bar-headed goose Hb-O-2 affinity have not previously been determined. An increase in breathing of the hypoxic and extremely cold air experienced by a bar-headed goose at altitude (due to the enhanced hypoxic ventilatory response in this species) could result in both reduced temperature and reduced levels of CO2 at the blood-gas interface in the lungs, enhancing O-2 loading. In addition, given the strenuous nature of flapping flight, particularly in thin air, blood leaving the exercising muscle should be warm and acidotic, facilitating O-2 unloading. To explore the possibility that features of blood biochemistry in this species could further enhance O-2 delivery, we determined the P-50 (the partial pressure of O-2 at which Hb is 50% saturated) of whole blood from bar-headed geese under conditions of varying temperature and [CO2]. We found that blood-O-2 affinity was highly temperature sensitive in bar-headed geese compared with other birds and mammals. Based on our analysis, temperature and pH effects acting on blood-O-2 affinity (cold alkalotic lungs and warm acidotic muscle) could increase O-2 delivery by twofold during sustained flapping flight at high altitudes compared with what would be delivered by blood at constant temperature and pH. C1 [Meir, Jessica U.; Milsom, William K.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada. RP Meir, JU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jmeir@partners.org FU National Science Foundation International Research Fellowship Program (IRFP) [OISE-0855669]; National Science Foundation RAPID Grant [OISE-1154099]; Natural Sciences and Engineering Research Council of Canada grant FX This work was funded by a National Science Foundation International Research Fellowship Program (IRFP) post-doctoral fellowship (OISE-0855669 to J.U.M.) and National Science Foundation RAPID Grant (OISE-1154099 to J.U.M.), and a Natural Sciences and Engineering Research Council of Canada grant (to W.K.M.). NR 34 TC 9 Z9 10 U1 12 U2 99 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JUN PY 2013 VL 216 IS 12 BP 2172 EP 2175 DI 10.1242/jeb.085282 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 154GG UT WOS:000319659900010 PM 23470665 ER PT J AU Chang, A Bowen, JL Buranosky, RA Frankel, RM Ghosh, N Rosenblum, MJ Thompson, S Green, ML AF Chang, Anna Bowen, Judith L. Buranosky, Raquel A. Frankel, Richard M. Ghosh, Nivedita Rosenblum, Michael J. Thompson, Sara Green, Michael L. TI Transforming Primary Care Training-Patient-Centered Medical Home Entrustable Professional Activities for Internal Medicine Residents SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; entrustable professional activities; graduate medical education; internal medicine; primary care ID TASK-FORCE; EDUCATION; ORGANIZATION; DIRECTORS; REFORM AB The U.S. faces a critical gap between residency training and clinical practice that affects the recruitment and preparation of internal medicine residents for primary care careers. The patient-centered medical home (PCMH) represents a new clinical microsystem that is being widely promoted and implemented to improve access, quality, and sustainability in primary care practice. We address two key questions regarding the training of internal medicine residents for practice in PCMHs. First, what are the educational implications of practice transformations to primary care home models? Second, what must we do differently to prepare internal medicine residents for their futures in PCMHs? The 2011 Society of General Internal Medicine (SGIM) PCMH Education Summit established seven work groups to address the following topics: resident workplace competencies, teamwork, continuity of care, assessment, faculty development, 'medical home builder' tools, and policy. The output from the competency work group was foundational for the work of other groups. The work group considered several educational frameworks, including developmental milestones, competencies, and entrustable professional activities (EPAs). The competency work group defined 25 internal medicine resident PCMH EPAs. The 2011 National Committee for Quality Assurance (NCQA) PCMH standards served as an organizing framework for EPAs. The list of PCMH EPAs has the potential to begin to transform the education of internal medicine residents for practice and leadership in the PCMH. It will guide curriculum development, learner assessment, and clinical practice redesign for academic health centers. C1 [Chang, Anna] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94118 USA. [Bowen, Judith L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bowen, Judith L.] Vet Hlth Adm Off Acad Affiliat, Washington, DC USA. [Buranosky, Raquel A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Frankel, Richard M.] Indiana Univ Sch Med, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. [Ghosh, Nivedita] Harvard Univ, Sch Med, Brigham & Womens Adv Primary Care Associates, Boston, MA USA. [Rosenblum, Michael J.] Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. [Thompson, Sara] Univ Washington, Sch Med, Grp Hlth Family Med Residency, Seattle, WA USA. [Green, Michael L.] Yale Univ, Sch Med, New Haven, CT USA. RP Chang, A (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA. EM anna.chang@ucsf.edu FU Josiah Macy Jr. Foundation; United Health Foundation FX Josiah Macy Jr. Foundation supported the Education Summit. Additional financial support for the Summit was provided by the United Health Foundation. The American College of Physicians, Primary Care Progress, and the Veterans Health Administration office of Academic Affiliations provided in-kind support. NR 39 TC 27 Z9 28 U1 3 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 IS 6 BP 801 EP 809 DI 10.1007/s11606-012-2193-3 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 151OB UT WOS:000319468800013 PM 22997002 ER PT J AU Kohler, MJ Amezaga, M Drozd, J Crowley, ST Gulanski, B Anderson, DR Fraenkel, L AF Kohler, Minna J. Amezaga, Matxalen Drozd, James Crowley, Susan T. Gulanski, Barbara Anderson, Daren R. Fraenkel, Liana TI Use of a Computerized Order Set to Increase Prescription of Calcium and Vitamin D Supplementation in Patients Receiving Glucocorticoids SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE glucocorticoid-induced osteoporosis; adherence; calcium; vitamin D; prednisone ID DECISION-SUPPORT-SYSTEMS; CORTICOSTEROID-INDUCED OSTEOPOROSIS; RHEUMATOID-ARTHRITIS; CONTROLLED-TRIAL; BONE LOSS; MANAGEMENT; PREVENTION; CARE; MEDICATION; FRACTURE AB American College of Rheumatology guidelines recommend that patients taking glucocorticoids also take calcium and vitamin D supplements, regardless of the dose or intended duration of glucocorticoid use, to decrease their risk of glucocorticoid-induced osteopenia or osteoporosis (GIOP). To increase the number of prescriptions made for calcium and vitamin D in patients who receive a prescription for glucocorticoids using an automated, computerized order set. Pre-post test design. A total of 1,041 outpatients receiving care at a single VA medical center. We developed an automated order set in which calcium and vitamin D were automatically co-ordered with glucocorticoid prescriptions of at least 2-week duration. We tested the impact of the order set by comparing the number of calcium and vitamin D prescriptions in patients taking glucocorticoids during a 12-month period before (T1) and after (T2) implementation. The automated order set could be modified by the treating physician, and it was not generated for patients with hypercalcemia. A total of 535 patients during T1 and 506 patients during T2 had a glucocorticoid prescription of at least 2-week duration. The percent of co-prescriptions for calcium increased from 37 to 49 % and vitamin D from 38 to 53 % (both p < 0.0001) after the new automated order set was implemented. Implementation of an automatic prescription for calcium and vitamin D supplementation modestly increases the number of patients on glucocorticoids who are prescribed calcium and vitamin D supplementation. C1 [Kohler, Minna J.] Harvard Univ, Sch Med, Div Rheumatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amezaga, Matxalen] Baylor Coll Med, Sect Rheumatol Allergy & Immunol, Houston, TX 77030 USA. [Drozd, James; Crowley, Susan T.; Gulanski, Barbara; Fraenkel, Liana] Vet Affairs VA Connecticut Healthcare Syst, West Haven, CT USA. [Crowley, Susan T.; Gulanski, Barbara; Fraenkel, Liana] Yale Univ, Sch Med, New Haven, CT USA. [Anderson, Daren R.] Community Hlth Ctr Inc, Middletown, CT USA. RP Kohler, MJ (reprint author), Harvard Univ, Sch Med, Div Rheumatol, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM mkohler@partners.org FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [5 T32 AR007107]; NIAMS [K24 AR060231-01] FX Dr. Kohler's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 5 T32 AR007107 Training Program for Investigative Rheumatology. Dr. Fraenkel is supported by the NIAMS K24 AR060231-01. NR 21 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2013 VL 28 IS 6 BP 825 EP 829 DI 10.1007/s11606-013-2360-1 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 151OB UT WOS:000319468800016 PM 23404201 ER PT J AU Arakaki, R Woo, E Kroshinsky, D AF Arakaki, R. Woo, E. Kroshinsky, D. TI The impact of dermatology consultations on antibiotic usage for suspected cases of cellulitis presenting to outpatient internal medicine offices SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Medical-Dermatology-Society CY FEB 28, 2013 CL Miami Beach, FL SP Med Dermatol Soc C1 [Arakaki, R.] Harvard Univ, Sch Med, Boston, MA USA. [Woo, E.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2013 VL 133 IS 6 MA 1 BP 1694 EP 1694 PG 1 WC Dermatology SC Dermatology GA 146VE UT WOS:000319121500047 ER PT J AU Dolfi, DV Mansfield, KD Polley, AM Doyle, SA Freeman, GJ Pircher, H Schmader, KE Wherry, EJ AF Dolfi, Douglas V. Mansfield, Kathleen D. Polley, Antonio M. Doyle, Susan A. Freeman, Gordon J. Pircher, Hanspeter Schmader, Kenneth E. Wherry, E. John TI Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE CD57; PD-1; KLRG-1; Eomes; CD107; exhaustion ID CHRONIC VIRAL-INFECTION; IFN-GAMMA PRODUCTION; TRANSCRIPTION FACTOR; HUMAN EFFECTOR; OLDER-ADULTS; MEMORY; EXPRESSION; EXHAUSTION; DIFFERENTIATION; PROTECTION AB Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects. C1 [Dolfi, Douglas V.; Mansfield, Kathleen D.; Polley, Antonio M.; Wherry, E. John] Univ Penn, Perelman Sch Med, Dept Microbiol, Inst Immunol, Philadelphia, PA 19104 USA. [Doyle, Susan A.; Schmader, Kenneth E.] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Doyle, Susan A.; Schmader, Kenneth E.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. [Pircher, Hanspeter] Univ Freiburg, Dept Immunol, D-79106 Freiburg, Germany. RP Wherry, EJ (reprint author), Univ Penn, PerelmanSch Med, Dept Microbiol, 421 Curie Blvd,Room 312, Philadelphia, PA 19104 USA. EM wherry@mail.med.upenn.edu FU U.S. National Institutes of Health [P01-A1078897, U19-AI082630]; U.S. grant [BAA 266200500030C] FX This work was funded by U.S. National Institutes of Health grants P01-A1078897 and U19-AI082630 to G.J.F. and E.J.W. and U.S. grant BAA 266200500030C to G.J.F., K. E. S., and E.J.W. The authors thank the members of the Wherry lab for discussions and critical reading of the manuscript and Sarah J. Ratcliffe for statistical analysis. NR 60 TC 21 Z9 21 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 2013 VL 93 IS 6 BP 825 EP 836 DI 10.1189/jlb.0912438 PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 155DZ UT WOS:000319727700003 PM 23440501 ER PT J AU Ponte, PR AF Ponte, Patricia Reid TI Structure, Process, and Empirical Outcomes-the Magnet (R) Journey of Continuous Improvement SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB The chairperson of the Commission on Magnet (R) Recognition provides an overview of current and future initiatives supporting cultures of excellence. The article examines the evolving focus on outcomes data and evidence, as well as the commitment of the commission to advancing nursing education at all levels. C1 [Ponte, Patricia Reid] Patient Care Serv, Boston, MA USA. [Ponte, Patricia Reid] Dana Farber Canc Inst, Boston, MA 02215 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Nursing Serv, Boston, MA 02115 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Clin Serv, Boston, MA 02115 USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1632, Boston, MA 02215 USA. EM pat_reid_ponte@dfci.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2013 VL 43 IS 6 BP 309 EP 310 DI 10.1097/NNA.0b013e3182942b49 PG 2 WC Nursing SC Nursing GA 152VS UT WOS:000319560100001 ER PT J AU Ponte, PR O'Neill, K AF Ponte, Patricia Reid O'Neill, Kathleen TI Hiring Into Advanced Practice Positions The Nurse Practitioner Versus Physician Assistants Debate SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PRIMARY-CARE OUTCOMES; DOCTORS; TRIAL AB Nurse practitioners (NPs) and physician assistants (PAs) have long been part of the care model at our institution. Over the years, however, we have demonstrated a preference for NPs based on the belief that they can better meet our patients' needs. A recent evaluation of our care model led us to question these preferential hiring practices. After carefully examining NP and PA education and licensure requirements, scope of practice, and roles at our institution, we concluded that similarities between the roles far outweighed the differences and that our preferential hiring practices should be replaced by an individualized approach, in which advanced practice positions are filled by whichever candidate best meets the role requirements. This inclusive and analytic approach may be a useful model for other nurse leaders considering the NP/PA question. C1 [Ponte, Patricia Reid] Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02215 USA. [Ponte, Patricia Reid] Dana Farber Canc Inst, Boston, MA 02215 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Oncol Nursing Serv, Boston, MA 02115 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Clin Serv, Boston, MA 02115 USA. [O'Neill, Kathleen] Simmons Sch Nursing & Hlth Sci Boston, Boston, MA USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1632, Boston, MA 02215 USA. EM pat_reid_ponte@dfci.harvard.edu NR 26 TC 1 Z9 1 U1 5 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2013 VL 43 IS 6 BP 329 EP 335 DI 10.1097/NNA.0b013e3182942c73 PG 7 WC Nursing SC Nursing GA 152VS UT WOS:000319560100008 ER PT J AU Gordon, PE Faquin, WC Lahey, E Kaban, LB AF Gordon, Paul E. Faquin, William C. Lahey, Edward Kaban, Leonard B. TI Floor-of-Mouth Dermoid Cysts: Report of 3 Variants and a Suggested Change in Terminology SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID GASTROINTESTINAL CYST AB Purpose: Dermoid cyst is a frequently used descriptive term, but its definition changes according to the clinician (eg, dermatologists, neurologists, gynecologists, oral and maxillofacial surgeons, and plastic surgeons). It is sometimes used synonymously with teratoma. In oral and maxillofacial surgery, it is applied to describe congenital floor-of-mouth cysts of 3 histologic types: epidermoid, dermoid, and teratoid. This terminology is confusing and has led to some ambiguity in the literature. The purpose of this report is to document 3 cases illustrating the utility of a more specific term, congenital germline fusion cyst of the floor of the mouth. Patients and Methods: Patients who presented with floor-of-mouth swelling were evaluated by history, clinical examination, and imaging studies (magnetic resonance imaging and computed tomography). Results: Three cases (1 epidermoid variant, 1 dermoid variant, and 1 teratoid variant) are documented to illustrate the new terminology. Conclusion: Congenital germline fusion cyst is more reflective of the embryologic origins of the lesion than dermoid cyst and is inclusive of all 3 histologic variants. (C) 2013 American Association of Oral and Maxillofacial Surgeons C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg,Med Sch, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol,Med Sch, Boston, MA 02115 USA. RP Gordon, PE (reprint author), 55 Fruit St,Wang ACC Suite 230, Boston, MA 02114 USA. EM pgordon4@partners.org FU Massachusetts General Hospital Department of Oral and Maxillofacial Education and Research Fund FX This work was funded by the Massachusetts General Hospital Department of Oral and Maxillofacial Education and Research Fund. NR 19 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2013 VL 71 IS 6 BP 1034 EP 1041 DI 10.1016/j.joms.2012.12.008 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 150IU UT WOS:000319384600009 PM 23434158 ER PT J AU Peacock, ZS Tricomi, BJ Murphy, BA Magill, JC Kaban, LB Troulis, MJ AF Peacock, Zachary S. Tricomi, Brad J. Murphy, Brian A. Magill, John C. Kaban, Leonard B. Troulis, Maria J. TI Automated Continuous Distraction Osteogenesis May Allow Faster Distraction Rates: A Preliminary Study SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CLINICAL-APPLICATION; BONE-FORMATION; ANIMAL-MODEL; DEVICE; FREQUENCY; MINIPIGS; CONDYLE; TISSUES; DISC; REGENERATION AB Purpose: To determine if automated continuous distraction osteogenesis (DO) at rates faster than 1 mm/day results in bone formation by clinical and radiographic criteria, in a minipig model. Materials and Methods: An automated, continuous, curvilinear distraction device was placed across a mandibular osteotomy in 10 minipigs. After 12 mm of distraction and 24 days of fixation, the animals were sacrificed and bone healing was evaluated. The continuous distraction rates were 1.5 mm/day (n = 5) and 3 mm/day (n = 5). A semiquantitative scale was used to assess the ex vivo clinical appearance of the distraction gap (3 = osteotomy not visible; 2 = <50% visible; 1 = >50% visible; 0 = 100% visible), stability (3 = no mobility; 2 and 1 = mobility in 1 plane or 2 planes, respectively; 0 = mobility in 3 planes), and radiographic density (4 = 100% of gap opaque; 3 = >75%; 2 = 50% to 75%; 1 = <50%; 0 = radiolucent). Groups of 4 minipigs distracted discontinuously at 1, 2, and 4 mm/day served as controls. Results: Automated, continuous DO at 1.5-mm/day and 3-mm/day had similar bone formation compared to discontinuous DO at 1-mm/day. The continuous DO 1.5-mm/day group had significantly higher scores for appearance and radiographic density compared with the discontinuous 4-mm/day group. The continuous DO 3-mm/day group had significantly higher scores for appearance and radiographic density compared with the discontinuous 4-mm/day group and greater stability compared with the discontinuous 2- and 4-mm/day groups. Conclusions: Results of this preliminary study indicate that continuous DO at rates of 1.5 and 3.0 mm/day produces better bone formation compared with discontinuous DO at rates faster than 1 mm/day. (C) 2013 American Association of Oral and Maxillofacial Surgeons C1 [Peacock, Zachary S.; Tricomi, Brad J.; Murphy, Brian A.; Magill, John C.; Kaban, Leonard B.; Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org FU NIH/NIDCR SBIR [5R44DE014803-03]; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Hanson Foundation (Boston, MA) FX This work was funded by NIH/NIDCR SBIR grant 5R44DE014803-03; the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; and the Hanson Foundation (Boston, MA). NR 43 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2013 VL 71 IS 6 BP 1073 EP 1084 DI 10.1016/j.joms.2012.11.015 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 150IU UT WOS:000319384600014 PM 23499159 ER PT J AU Mull, HJ Borzecki, AM Hickson, K Itani, KMF Rosen, AK AF Mull, Hillary J. Borzecki, Ann M. Hickson, Kathleen Itani, Kamal M. F. Rosen, Amy K. TI Development and Testing of Tools to Detect Ambulatory Surgical Adverse Events SO JOURNAL OF PATIENT SAFETY LA English DT Article DE surgical adverse event; trigger tool; ambulatory surgery; NSQIP ID QUALITY IMPROVEMENT PROGRAM; RETURN HOSPITAL VISITS; OF-VETERANS-AFFAIRS; POSTDISCHARGE SYMPTOMS; OUTPATIENT SURGERY; AMERICAN-COLLEGE; CARE; READMISSIONS AB Objectives: Numerous health-care systems in the United States, including the Veterans Health Administration (VA), use the National Surgical Quality Improvement Program (NSQIP) to detect surgical adverse events (AEs). VASQIP sampling methodology excludes many routine ambulatory surgeries from review. Triggers, algorithms derived from clinical logic to flag cases where AEs have most likely occurred, could complement VASQIP by detecting a higher yield of ambulatory surgeries with a true surgical AE. Methods: We developed and tested a set of ambulatory surgical AE trigger algorithms using a sample of fiscal year 2008 ambulatory surgeries from the VA Boston Healthcare System. We used VA Boston VASQIP-assessed cases to refine triggers and VASQIP-excluded cases to test how many trigger-flagged surgeries had a nurse chart reviewdetected surgical AE. Chart review was performed using the VA electronic medical record. We calculated the ratio of cases with a true surgical AE over flagged cases (i.e., the positive predictive value [PPV]), and the 95% confidence interval for each trigger. Results: Compared with the VASQIP rate (9 AEs, or 2.8%, of the 322 charts assessed), nurse chart review of the 198 trigger-flagged surgeries yielded more cases with at least 1 AE (47 surgeries with an AE, or 6.0%, of the 782 VASQIP-excluded ambulatory surgeries). Individual trigger PPVs ranged from 12.4% to 58.3%. Conclusions: In comparison with VASQIP, our set of triggers identified a higher rate of surgeries with AEs in fewer chart-reviewed cases. Because our results are based on a relatively small sample, further research is necessary to confirm these findings. C1 [Mull, Hillary J.; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA. [Mull, Hillary J.; Borzecki, Ann M.; Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Borzecki, Ann M.; Hickson, Kathleen] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Hickson, Kathleen] VA Boston Healthcare Syst, West Roxbury, MA USA. [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, West Roxbury, MA USA. [Borzecki, Ann M.; Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Mull, HJ (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM hjmull@bu.edu FU VA Boston Healthcare System Department of Surgery FX This research was funded through the VA Boston Healthcare System Department of Surgery. NR 39 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD JUN PY 2013 VL 9 IS 2 BP 96 EP 102 DI 10.1097/PTS.0b013e31827d1a88 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 151FI UT WOS:000319445700007 PM 23370221 ER PT J AU Green, AD Belkind-Gerson, J Surjanhata, BC Mousa, H Kuo, B Di Lorenzo, C AF Green, Alex D. Belkind-Gerson, Jaime Surjanhata, Brian C. Mousa, Hayat Kuo, Braden Di Lorenzo, Carlo TI Wireless Motility Capsule Test in Children with Upper Gastrointestinal Symptoms SO JOURNAL OF PEDIATRICS LA English DT Article ID HEALTHY; TRANSIT; GASTROPARESIS AB Objective To compare scintigraphic gastric emptying and antroduodenal manometry (ADM) studies with the wireless motility capsule test in symptomatic pediatric patients. Study design Patients aged 8-17 years with severe upper gastrointestinal symptoms (ie, nausea, vomiting, retching, abdominal pain) referred for ADM were recruited. A standardized protocol for ADM was used. On a different day, participants were given a standardized meal and then swallowed the wireless motility capsule. A wireless receiver unit worn during the study recorded transmitted data. If not performed previously, a 2-hour scintigraphic gastric emptying study was completed at the time of ADM testing. Results A total of 22 patients were recruited, of whom 21 had complete scintigraphic gastric emptying study data and 20 had complete ADM data. The wireless motility capsule test had 100% sensitivity and 50% specificity in detecting gastroparesis compared with the 2-hour scintigraphic gastric emptying study. The wireless motility capsule test detected motor abnormalities in 17 patients, compared with 10 detected by ADM. Dichotomous comparison yielded a diagnostic difference between ADM and the wireless motility capsule test (P<.01). Migrating motor complexes were recognized in all patients by both ADM and the wireless motility capsule test. The wireless motility capsule test was well tolerated in all patients, and there were no side effects. Conclusion In symptomatic pediatric patients, the wireless motility capsule test is highly sensitive compared with scintigraphic gastric emptying studies in detecting gastroparesis, and seems to be more sensitive than ADM in detecting motor abnormalities. C1 [Green, Alex D.; Mousa, Hayat; Di Lorenzo, Carlo] Ohio State Univ, Nationwide Childrens Hosp, Dept Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA. [Belkind-Gerson, Jaime] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Gastroenterol, Boston, MA USA. [Surjanhata, Brian C.; Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. RP Green, AD (reprint author), 500 Parnassus Ave, San Francisco, CA 94143 USA. EM alex.green@ucsf.edu NR 14 TC 8 Z9 8 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2013 VL 162 IS 6 BP 1181 EP 1187 DI 10.1016/j.jpeds.2012.11.040 PG 7 WC Pediatrics SC Pediatrics GA 152AV UT WOS:000319502700021 PM 23290514 ER PT J AU Smith, VC Hwang, SS Dukhovny, D Young, S Pursley, DM AF Smith, V. C. Hwang, S. S. Dukhovny, D. Young, S. Pursley, D. M. TI Neonatal intensive care unit discharge preparation, family readiness and infant outcomes: connecting the dots SO JOURNAL OF PERINATOLOGY LA English DT Article DE intensive care units neonatal; intensive care neonatal; infant preterm; newborn readiness; patient discharge; education ID BIRTH-WEIGHT INFANTS; HIGH-RISK NEONATE; HOSPITAL DISCHARGE; PRETERM INFANTS; RANDOMIZED-TRIAL; CENTERED CARE; BRONCHOPULMONARY DYSPLASIA; POSTPARTUM DISCHARGE; MOTHERS; INTERVENTION AB Neonatal intensive care unit (NICU) discharge readiness is defined as the masterful attainment of technical skills and knowledge, emotional comfort, and confidence with infant care by the primary caregivers at the time of discharge. NICU discharge preparation is the process of facilitating comfort and confidence as well as the acquisition of knowledge and skills to successfully make the transition from the NICU to home. In this paper, we first review the literature about discharge readiness as it relates to the NICU population. Understanding that discharge readiness is achieved, in part, through successful discharge preparation, we then outline an approach to NICU discharge preparation. C1 [Smith, V. C.; Dukhovny, D.; Pursley, D. M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neonatol, Boston, MA 02215 USA. [Hwang, S. S.] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. [Young, S.] Beth Israel Deaconess Med Ctr, Dept Nursing, Boston, MA 02215 USA. RP Smith, VC (reprint author), Harvard Univ, BIDMC, Sch Med, Dept Neonatol, 330 Brookline Ave,Rose 318, Boston, MA 02215 USA. EM vsmith1@bidmc.harvard.edu NR 52 TC 13 Z9 15 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD JUN PY 2013 VL 33 IS 6 BP 415 EP 421 DI 10.1038/jp.2013.23 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 154FM UT WOS:000319657300001 PM 23492936 ER PT J AU Lubelski, D Abdullah, KG Steinmetz, MP Masters, F Benzel, EC Mroz, TE Shin, JH AF Lubelski, Daniel Abdullah, Kalil G. Steinmetz, Michael P. Masters, Frank Benzel, Edward C. Mroz, Thomas E. Shin, John H. TI Lateral Extracavitary, Costotransversectomy, and Transthoracic Thoracotomy Approaches to the Thoracic Spine Review of Techniques and Complications SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Review DE lateral extracavitary; costotransversectomy; thoracotomy; thoracic spine; spine complications ID SUBARACHNOID-PLEURAL FISTULA; LUMBAR SPINE; SURGICAL-TREATMENT; THORACOLUMBAR SPINE; DISC HERNIATIONS; POSTEROLATERAL APPROACH; CORD DECOMPRESSION; POSTERIOR APPROACH; ANTERIOR EXPOSURE; MANAGEMENT AB Study Design: Systematic review. Objective: The authors review complications, as reported in the literature, associated with ventral and posterolateral approaches to the thoracic spine. Summary of Background: The lateral extracavitary, costotransversectomy, and transthoracic thoracotomy techniques allow surgeons to access the ventral thoracic spine for a wide range of spinal disorders including tumor, degeneration, trauma, and infection. Although the transthoracic thoracotomy has been used traditionally to reach the ventral thoracic spine when access to the vertebral body is required, modifications to the various dorsal approaches have enabled surgeons to achieve goals of decompression, reconstruction, and stabilization through a single approach. Methods: A systematic Medline search from 1991 to 2011 was performed to identify series reporting clinical data related to these surgical approaches. The morbidity associated with each approach is reviewed and strategies for complications avoidance are discussed. Results: Four thousand six hundred seventy-seven articles that assessed outcomes of the approaches to the thoracic spine were identified; of these 31 studies that consisted of 774 patients were selected for inclusion. A mean complication rate of 39%, 17%, and 15% for thoracotomy, lateral extracavitary, and costotransversectomy, respectively, was determined. The thoracotomy approach had the highest reoperation (3.5%) and mortality rates (1.5%). The specific complications and neurological outcomes were categorized. Conclusions: Outcomes of the surgical approaches to the thoracic spine have been reported with great detail in the literature. There are limited studies comparing the respective advantages and disadvantages and the differences in technique and outcome between these approaches. The present review suggests that in contrast to the historical experience of the laminectomy for thoracic spine disorders, these alternative approaches are safe and rarely associated with neurological deterioration. The differences between these approaches are based on their complication profiles. A thorough understanding of the regional anatomy will help avoid approach-related complications. C1 [Lubelski, Daniel; Abdullah, Kalil G.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Lubelski, Daniel; Abdullah, Kalil G.; Steinmetz, Michael P.; Masters, Frank] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Steinmetz, Michael P.] Metrohlth Med Ctr, Cleveland, OH USA. [Benzel, Edward C.; Mroz, Thomas E.] Ctr Spine Hlth, Dept Neurosurg, Neurol Inst, Cleveland, OH USA. [Mroz, Thomas E.] Cleveland Clin, Dept Orthoped Surg, Cleveland, OH 44106 USA. [Shin, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Shin, JH (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,WAC 745, Boston, MA 02114 USA. EM shin.john@mgh.harvard.edu NR 76 TC 9 Z9 12 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD JUN PY 2013 VL 26 IS 4 BP 222 EP 232 DI 10.1097/BSD.0b013e31823f3139 PG 11 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 151IX UT WOS:000319455000015 PM 22143047 ER PT J AU Niess, H Conrad, C Kleespies, A Haas, F Bao, Q Jauch, KW Graeb, C Bruns, CJ AF Niess, Hanno Conrad, Claudius Kleespies, Axel Haas, Florian Bao, Qi Jauch, Karl-Walter Graeb, Christian Bruns, Christiane J. TI Surgery for Metastasis to the Pancreas: Is it Safe and Effective? SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE pancreatic metastasis; metastasectomy; renal cell carcinoma; pancreatic surgery ID RENAL-CELL CARCINOMA; OF-THE-LITERATURE; PULMONARY RESECTION; SURGICAL-TREATMENT; TUMORS; SURVIVAL; COMPLICATIONS AB Background Pancreatic metastases are rare and only sparse data exists on treatment options. After recent advances in pancreatic surgery, metastasectomies have become promising treatment alternatives. Methods Twenty-six patients underwent pancreatic metastasectomy between 1991 and 2010 at our institution. Data was evaluated retrospectively. Results Renal cell carcinoma was the most common origin of pancreatic metastases (n=16; 62%). Other primaries include gall bladder carcinoma, leiomyosarcoma, colon cancer (all n=2), and others. The median time interval between primary tumor and pancreatic resection was 5.3 years [024]. Eleven pancreatic head resections (42%), fourteen distal pancreatectomies (54%), and one total pancreatectomy were performed (4%). The estimated 3- and 5-year survival rates were 73.2% and 52.3%, respectively. The estimated median overall survival was 63 months (CI: 37.888.1 months). There' was no perioperative death. The complication rate and relaparotomy rate was 31% and 19%, respectively. Patients suffering from synchronous metastases at the time of pancreatic surgery had a statistically significant shorter median overall survival time (11 months vs. 64 months). Conclusions Despite the operative risk involved, we believe that pancreatic resection should be considered in selected patients with good performance status, stable disease and isolated pancreatic metastases. J. Surg. Oncol. 2013;107:859864. (c) 2013 Wiley Periodicals, Inc. C1 [Niess, Hanno; Kleespies, Axel; Haas, Florian; Bao, Qi; Jauch, Karl-Walter; Bruns, Christiane J.] Univ Munich, Dept Surg, Munich, Germany. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Graeb, Christian] Klinikum Hof, Dept Surg, Hof, Germany. RP Conrad, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM cconrad@partners.org NR 24 TC 13 Z9 13 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN PY 2013 VL 107 IS 8 BP 859 EP 864 DI 10.1002/jso.23333 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 150WH UT WOS:000319421700012 PM 23637007 ER PT J AU Akins, CW AF Akins, Cary W. TI The Impact of Aortic Valve Replacement for Aortic Stenosis on Mitral Valve Dynamics: A Surgeon's View SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID HEART-VALVE C1 [Akins, Cary W.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Akins, Cary W.] Harvard Univ, Sch Med, Boston, MA USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, 55 Fruit St, Boston, MA 02114 USA. EM caryakins@comcast.net NR 9 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUN PY 2013 VL 26 IS 6 BP 615 EP 617 DI 10.1016/j.echo.2013.04.006 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151YL UT WOS:000319496200008 PM 23711343 ER PT J AU Wright, CD AF Wright, Cameron D. TI Historical perspectives of The American Association for Thoracic Surgery: Herbert Sloan SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2013 VL 145 IS 6 BP 1428 EP 1430 DI 10.1016/j.jtcvs.2013.04.001 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 146CK UT WOS:000319066300015 PM 23583173 ER PT J AU Yechoor, P Blaustein, AS Bakaeen, FG Cornwell, LD Coselli, JS LeMaire, SA Chu, D AF Yechoor, Poornima Blaustein, Alvin S. Bakaeen, Faisal G. Cornwell, Lorraine D. Coselli, Joseph S. LeMaire, Scott A. Chu, Danny TI The natural history of moderate aortic stenosis in a veteran population SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CARDIOVASCULAR MORTALITY; VALVE DISEASE; PROGRESSION; MANAGEMENT; MILD AB Objective: Our objective was to evaluate the natural history of moderate aortic stenosis in veterans-a unique patient population with significant comorbidities. Methods: We retrospectively reviewed the records of all patients who underwent echocardiography at a single veterans affairs hospital during 2006. We identified consecutive patients who had moderate aortic stenosis as indicated by a mean transaortic gradient of 25 to 40 mm Hg, peak aortic jet velocity of 3 to 4 m/s, or aortic valve area of 1.0 to 1.5 cm(2). The primary end point was defined as survival without aortic valve replacement. Results: Of the 104 patients (mean age, 74 +/- 10 years), 49% had diabetes, 21% had peripheral vascular disease, 21% were current smokers, 18% had chronic obstructive pulmonary disease, 60% had coronary artery disease, 89% had hypertension, and 31% had a body mass index of 30 kg/m(2) or more. Mean ejection fraction was 49% +/- 12%. During the mean follow-up period of 22 months (range, 1-67 months), 30% of patients underwent aortic valve replacement-26% for symptomatic severe aortic stenosis and 4% concomitantly with coronary artery bypass grafting as the primary indicated operation-and 61% died. Event-free survivals were 48%, 24%, and 15% at 1, 3, and 5 years, respectively. Conclusions: Our cohort of military veteran patients had significant comorbidities. Event-free survival for such patients who have moderate aortic stenosis is significantly lower than previously reported data suggest. Within this unique group of patients, identifying factors that accelerate the progression of moderate aortic stenosis would help surgeons select patients who may benefit from early aortic valve replacement for moderate aortic stenosis. C1 St Lukes Episcopal Hosp, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Baylor Coll Med,Div Cardiothorac Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Baylor Coll Med,Div Cardiol, Houston, TX 77030 USA. RP Chu, D (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiothorac Surg, 1 Baylor Plaza, Houston, TX 77030 USA. EM dchumd@gmail.com FU Michael E. DeBakey Veterans Affairs Health Services Research & Development Center of Excellence [HFP90-020]; Baylor College of Medicine FX Funded by the Michael E. DeBakey Veterans Affairs Health Services Research & Development Center of Excellence (HFP90-020); internal funding from Baylor College of Medicine. NR 25 TC 4 Z9 4 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2013 VL 145 IS 6 BP 1550 EP 1553 DI 10.1016/j.jtcvs.2012.05.013 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 146CK UT WOS:000319066300038 PM 22664178 ER PT J AU Barshes, NR Ozaki, CK Kougias, P Belkin, M AF Barshes, Neal R. Ozaki, C. Keith Kougias, Panos Belkin, Michael TI A cost-effectiveness analysis of infrainguinal bypass in the absence of great saphenous vein conduit SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CRITICAL LIMB ISCHEMIA; INFRAPOPLITEAL ARTERIES; POLYTETRAFLUOROETHYLENE BYPASS; TIBIAL BYPASS; SALVAGE; GRAFTS; METAANALYSIS; MULTICENTER; MANAGEMENT; PATCH AB Background: Good-quality great saphenous vein (GSV) is the preferred conduit for infrainguinal surgical revascularizations, but it is not available in all patients. We sought to identify the alternative conduit that would maximize cost-effectiveness in the context of infrapopliteal bypass for critical limb ischemia and nonhealing foot wounds. Methods: A Markov model was used to create a detailed simulation of 10-year outcomes in a hypothetical Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT) III-type patient cohort undergoing infrainguinal bypass for nonhealing foot wounds. The following management options were evaluated: (1) conservative therapy (local wound care, amputation as needed); (2) primary amputation; (3) bypass with autologous alternative vein (AAV), including arm or lesser saphenous vein; (4) bypass with GSV <3 mm in diameter; (5) bypass with polytetrafluoroethylene (PTFE); (6) cryopreserved venous allograft; and (7) cryopreserved arterial allograft. Estimates of 10-year total costs were incorporated into the model. Cost-effectiveness was measured in terms of incremental United States dollars per additional year of ambulation. Results: Bypass with AAV had the highest effectiveness as measured in median years of ambulation. After primary amputation, bypass with PTFE had the lowest total costs. With incremental cost-effectiveness ratios of $5325 and $21,228, bypass with PTFE or AAV appeared to be cost-effective alternatives to conservative therapy for nonhealing ischemic wounds. Primary amputation, GSV <3 mm, and allograft options were dominated (ie, more costly and less effective). Primary amputation was weakly dominated. Conclusions: Bypass with PTFE or AAV appears to be a cost-effective option for the management of critical limb ischemia and nonhealing foot wounds when good-quality GSV is not available. C1 [Barshes, Neal R.; Kougias, Panos] Baylor Coll Med, Div Vasc & Endovasc Surg, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Ozaki, C. Keith; Belkin, Michael] Brigham & Womens Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. RP Barshes, NR (reprint author), Baylor Coll Med, Div Vasc & Endovasc Surg, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. EM nbarshes@bcm.tmc.edu NR 25 TC 6 Z9 6 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2013 VL 57 IS 6 BP 1466 EP 1470 DI 10.1016/j.jvs.2012.11.115 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 150KN UT WOS:000319389400003 PM 23395205 ER PT J AU Gasper, WJ Reilly, LM Rapp, JH Grenon, SM Hiramoto, JS Sobel, JD Chuter, TAM AF Gasper, Warren J. Reilly, Linda M. Rapp, Joseph H. Grenon, S. Marlene Hiramoto, Jade S. Sobel, Julia D. Chuter, Timothy A. M. TI Assessing the anatomic applicability of the multibranched endovascular repair of thoracoabdominal aortic aneurysm technique SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Western-Vascular-Society CY SEP 22-25, 2012 CL Park City, UT SP Western Vasc Soc ID UNITED-STATES; STENT GRAFTS; EXPERIENCE AB Background: Multibranched endovascular aneurysm repair (MBEVAR) has the potential to lower the morbidity and mortality rates of thoracoabdominal aneurysm repair, but the applicability of the technique is unknown. Our aim was to estimate the prevalence of anatomic suitability for MBEVAR. Methods: Retrospective review of patients referred for a prospective trial of MBEVAR between November 2005 and July 2012. Anatomic suitability was assessed on three-dimensional computed tomography scan reconstructions according to the current criteria for a custom-made stent graft or a fixed, off-the-shelf stent graft in both standard (22F) and low-profile (18F) delivery systems. Results: A total of 250 contrast-enhanced computed tomography scans were reviewed, 49 of which were excluded due to inadequate aneurysm size. Of 201 candidates for repair, 149 (74%) were men and 86 (43%) had Crawford classification type IV/paravisceral aneurysms; 109 (58%) were anatomically suitable for a single-stage repair with a custom-made, low-profile stent graft. Another 58 (29%) could have been made suitable for MBEVAR with an adjunct procedure, including angiogram with visceral or renal artery stenting (n = 23), carotid-subclavian bypass (n = 5), or iliac bypass for device insertion (n = 17), or to preserve internal iliac artery flow because of an iliac aneurysm (n = 9), or dissection (n = 8). There was no association between suitability and gender, aneurysm diameter, or type. However, women were significantly more likely to need a conduit or low-profile device (P = .003). Patients with type B aortic dissections were significantly less likely to have anatomy suitable for repair (P = .035) and more likely to require a multistage repair. Thirty-four patients would have been unsuitable for repair because of renal artery anatomy (n = 14), visceral artery anatomy (n = 4), lack of a proximal landing zone due to an arch aneurysm (n = 7), or inadequate access arteries (n = 9). The low-profile device increased the number of patients who would have been suitable for a single-stage repair by 16. The off-the-shelf graft has the advantage of a faster assessment-to-treatment time, but only 64 patients would have been suitable for a single-stage repair and another 30 could have been made suitable with an adjunct procedure. Conclusions: Most patients would have been suitable or could have been made suitable for a thoracoabdominal stent graft using current anatomic criteria. The applicability of MBEVAR will continue to change as the experience with the technique grows and devices evolve, as evidenced by the potential reduction in iliac bypasses after the introduction of a low-profile device and the ability to treat symptomatic or urgent patients with the off-the-shelf device. C1 [Gasper, Warren J.; Reilly, Linda M.; Hiramoto, Jade S.; Sobel, Julia D.; Chuter, Timothy A. M.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Rapp, Joseph H.; Grenon, S. Marlene] San Francisco VA Med Ctr, Vasc Surg Sect, San Francisco, CA USA. RP Gasper, WJ (reprint author), Univ Calif San Francisco, Div Vasc & Endovasc Surg, 400 Parnassus Ave,Box 0222, San Francisco, CA 94143 USA. EM Warren.Gasper@ucsf.edu NR 23 TC 17 Z9 17 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2013 VL 57 IS 6 BP 1553 EP 1558 DI 10.1016/j.jvs.2012.12.021 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 150KN UT WOS:000319389400017 PM 23395201 ER PT J AU Berry, K Ioannou, GN AF Berry, Kristin Ioannou, George N. TI Serum alpha-fetoprotein level independently predicts posttransplant survival in patients with hepatocellular carcinoma SO LIVER TRANSPLANTATION LA English DT Article ID LIVER-TRANSPLANTATION; CIRRHOSIS; VALIDATION; ALLOCATION AB We aimed to determine whether combining serum alpha-fetoprotein (AFP) level with hepatocellular carcinoma (HCC) tumor burden would allow better stratification of posttransplant survival for patients with HCC undergoing liver transplantation. Adjusting for donor and recipient characteristics, we calculated the risk of posttransplant mortality associated with serum AFP level or HCC tumor burden for all first-time adult liver transplants performed in the United States between 2002 and 2011 (n=45,267). Serum AFP level, rather than tumor burden, was the tumor characteristic most strongly associated with posttransplant survival. Although recipients with HCC and a serum AFP level15 ng/mL at the time of transplantation had no excess posttransplant mortality [adjusted hazard ratio (AHR)=1.02, 95% confidence interval (CI)=0.93-1.12], patients with a serum AFP level of 16 to 65 ng/mL (AHR=1.38, 95% CI=1.23-1.54), patients with a serum AFP level of 66 to 320 ng/mL (AHR=1.65, 95% CI=1.45-1.88), and patients with a serum AFP level>320 ng/mL (AHR=2.37, 95% CI=2.06-2.73) had progressively worse posttransplant mortality in comparison with recipients without HCC. Patients with a tumor burden exceeding the Milan criteria (who are usually excluded from transplantation) had excellent posttransplant survival if their serum AFP level was 0 to 15 ng/mL (AHR=0.97, 95% CI=0.66-1.43). In contrast, patients within the Milan criteria (who are routinely considered to be transplant candidates) had poor survival if their serum AFP level was substantially elevated (for a serum AFP level66 ng/mL, AHR=1.93, 95% CI=1.74-2.15). Changes in serum AFP level while patients were on the waiting list corresponded closely to changes in posttransplant mortality. In conclusion, the absolute serum AFP level and changes in the serum AFP level strongly predict posttransplant survival independently of the tumor burden. We hope that these data, in combination with other factors, can be used to inform future studies and ongoing discussions aimed at improving the eligibility criteria for liver transplantation for patients with HCC. Liver Transpl 19:634-645, 2013. (c) 2013 AASLD. C1 [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, 1660 South Columbian Way,S-111 Gastro, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Veterans Affairs Office of Research and Development; Health Resources and Services Administration [231-00-0115] FX This study was supported by the Research Enhancement Award Program of the Veterans Affairs Office of Research and Development.; This research is based on data derived from the United Network for Organ Sharing in October 2011. This work was supported in part by Health Resources and Services Administration contract 231-00-0115. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 16 TC 37 Z9 37 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2013 VL 19 IS 6 BP 634 EP 645 DI 10.1002/lt.23652 PG 12 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 152FZ UT WOS:000319518000010 PM 23536495 ER PT J AU Tewarie, NMSB Burgers, IAV Dawood, Y den Boon, HC den Brok, MGHE Klunder, JH Koopmans, KB Rademaker, E van den Broek, HB van den Bersselaar, SM Witjes, JJ Van Noorden, CJF Atai, NA AF Tewarie, Nishita M. S. Baldewpersad Burgers, Ilsa A. V. Dawood, Yousif den Boon, Hannah C. den Brok, Melina G. H. E. Klunder, Jet H. Koopmans, Kristijn B. Rademaker, Emma van den Broek, Hans B. van den Bersselaar, Sil M. Witjes, Julia J. Van Noorden, Cornelis J. F. Atai, Nadia A. TI NADP(+)-dependent IDH1(R132) mutation and its relevance for glioma patient survival SO MEDICAL HYPOTHESES LA English DT Article ID ISOCITRATE DEHYDROGENASE 1; MGMT PROMOTER METHYLATION; HIGH-GRADE GLIOMAS; IDH2 MUTATIONS; ONCOMETABOLITE 2-HYDROXYGLUTARATE; GENETIC ALTERATIONS; MUTANT IDH1; IN-VIVO; GLIOBLASTOMA; CANCER AB The isocitrate dehydrogenase 1 (IDH1) mutation occurs in high frequency in glioma and secondary glioblastoma (GBM). Mutated IDH1 produces the oncometabolite 2-hydroxyglutarate rather than a-ketoglutarate or isocitrate. The oncometabolite is considered to be the major cause of the association between the IDH1 mutation and gliomagenesis. On the other hand, the IDH1 mutation in GBM is associated with prolonged patient survival. This association is not well understood yet but IDH1 involvement in epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme is considered to be an important mechanism. However, it was shown recently that the IDH1 mutation and MGMT silencing are independent prognostic factors. Here, we hypothesize that the IDH1 mutation reduces the capacity to produce NADPH and thus reduces the capacity to scavenge reactive oxygen species that are generated during irradiation and chemotherapy. IDH1 activity is responsible for two-thirds of the NADPH production capacity in normal brain, whereas the IDH1 mutation reduces this capacity by almost 40%. Therefore, we hypothesize that the reduced NADPH production capacity due to the IDH1 mutation renders GBM cells more vulnerable to irradiation and chemotherapy thus prolonging survival of the patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Tewarie, Nishita M. S. Baldewpersad; Burgers, Ilsa A. V.; Dawood, Yousif; den Boon, Hannah C.; den Brok, Melina G. H. E.; Klunder, Jet H.; Koopmans, Kristijn B.; Rademaker, Emma; van den Broek, Hans B.; van den Bersselaar, Sil M.; Witjes, Julia J.; Van Noorden, Cornelis J. F.; Atai, Nadia A.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Atai, Nadia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci,Dept Neurol, Boston, MA 02129 USA. RP Van Noorden, CJF (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. FU Academic Medical Center (AMC) FX For the preparation of the manuscript the authors wish to thank M. Arendse. This study was supported by an Academic Medical Center (AMC) scholarship (NAA). NR 52 TC 8 Z9 8 U1 0 U2 18 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUN PY 2013 VL 80 IS 6 BP 728 EP 731 DI 10.1016/j.mehy.2013.02.022 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 153WZ UT WOS:000319634800012 ER PT J AU Carbonell, CF Chitnis, T AF Carbonell, C. Fernandez Chitnis, T. TI Inflammatory demyelinating diseases in children: an update SO MINERVA PEDIATRICA LA English DT Article DE Child; Multiple sclerosis; Neuromyelitis optica; Encephalomyelitis ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; PEDIATRIC MULTIPLE-SCLEROSIS; ACUTE TRANSVERSE MYELITIS; NEUROMYELITIS-OPTICA-IGG; TERM-FOLLOW-UP; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CLINICALLY ISOLATED SYNDROMES; EPSTEIN-BARR-VIRUS; B-CELL FOLLICLES; EARLY-ONSET AB Inflammatory demyelinating diseases (DD) affecting the central nervous system (CNS) are increasingly recognized in children. During the past decade significant advances have been made in this field. Pediatric DD are important not just because 3-5% of MS cases are diagnosed in childhood, but also because their pathogenesis may provide unique insights into the earliest events and triggers of acquired CNS DD. The purpose of this article is to offer an update into pediatric DD for the general pediatrician and child neurologist. Current evidence on epidemiology, pathology, diagnosis, management and prognosis are reviewed for both monophasic (ADEM and CIS) and polyphasic/chronic DD (MS and NMO). We also review new research advances including novel biomarkers and treatments from the latest literature. C1 [Carbonell, C. Fernandez; Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Dept Child Neurol, Boston, MA 02114 USA. [Carbonell, C. Fernandez; Chitnis, T.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Chitnis, T (reprint author), 75 Fruit St,ACC708, Boston, MA 02114 USA. EM tchitnis@partners.org NR 199 TC 1 Z9 1 U1 2 U2 14 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4946 EI 1827-1715 J9 MINERVA PEDIATR JI Minerva Pediat. PD JUN PY 2013 VL 65 IS 3 BP 307 EP 323 PG 17 WC Pediatrics SC Pediatrics GA 152JS UT WOS:000319528600007 ER PT J AU Abels, ER van der Vos, KE Skog, J Hickman, SE El Khoury, J Breakefield, XO AF Abels, Erik R. van der Vos, Kristan E. Skog, Johan Hickman, Suzanne E. El Khoury, Joseph Breakefield, Xandra O. TI Glioblastoma Transfer miRNAs into Microglial Cells through Extracellular Vesicles SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Abels, Erik R.; van der Vos, Kristan E.; Skog, Johan; Hickman, Suzanne E.; El Khoury, Joseph; Breakefield, Xandra O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skog, Johan] Columbia Univ, Med Ctr, Exosome Diagnost Inc, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 304 BP S116 EP S117 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400303 ER PT J AU Badr, CE Amante, R Van Hoppe, S Tannous, BA AF Badr, Christian E. Amante, Romain Van Hoppe, Stephanie Tannous, Bakhos A. TI An RNAi Screening Platform To Identify Modulators of Glioma Stem Cells Viability and Differentiation SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Badr, Christian E.; Amante, Romain; Van Hoppe, Stephanie; Tannous, Bakhos A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2013 VL 21 SU 1 MA 458 BP S176 EP S176 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400457 ER PT J AU Golebiowski, D van der Bom, IMJ Kwon, CS Maitland, S Kuhn, AL Bishop, N Curren, E Silva, N Miller, A Westmoreland, S Gounis, M Martin, DR Asaad, W Sena-Esteves, M AF Golebiowski, Diane van der Bom, Imramsjah M. J. Kwon, Churl-Su Maitland, Stacy Kuehn, Anna Luisa Bishop, Nina Curren, Elizabeth Silva, Nilsa Miller, Andrew Westmoreland, Susan Gounis, Matthew Martin, Douglas R. Asaad, Wael Sena-Esteves, Miguel TI Safety Study of Intracranial AAVrh8-Mediated Gene Transfer of beta-Hexosaminidase in Non-Human Primates SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Golebiowski, Diane; van der Bom, Imramsjah M. J.; Maitland, Stacy; Kuehn, Anna Luisa; Bishop, Nina; Gounis, Matthew; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Worcester, MA USA. [Kwon, Churl-Su] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Curren, Elizabeth; Silva, Nilsa; Miller, Andrew; Westmoreland, Susan] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Martin, Douglas R.] Auburn Univ, Scott Ritchey Res Ctr, Auburn, AL 36849 USA. [Asaad, Wael] Rhode Isl Hosp, Providence, RI USA. [Asaad, Wael] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 387 BP S149 EP S149 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400386 ER PT J AU Hudry, E Dashkoff, J Lee, A Takeda, S Koffie, RM Hashimoto, T Scheel, M Spires-Jones, T Arbel-Ornath, M Betensky, RA Davidson, BL Hyman, BT AF Hudry, Eloise Dashkoff, Jonathan Lee, Allyson Takeda, Shuko Koffie, Robert M. Hashimoto, Tadafumi Scheel, Maria Spires-Jones, Tara Arbel-Ornath, Michal Betensky, Rebecca A. Davidson, Beverly L. Hyman, Bradley T. TI Gene Transfer of Human Apoe epsilon 2 Alleviate the Progression of Amyloid Deposition In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Hudry, Eloise; Dashkoff, Jonathan; Lee, Allyson; Takeda, Shuko; Koffie, Robert M.; Hashimoto, Tadafumi; Spires-Jones, Tara; Arbel-Ornath, Michal; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Hudry, Eloise; Dashkoff, Jonathan; Lee, Allyson; Takeda, Shuko; Koffie, Robert M.; Hashimoto, Tadafumi; Spires-Jones, Tara; Arbel-Ornath, Michal; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA USA. [Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. [Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Physiol & Mol Biophys, Iowa City, IA USA. [Betensky, Rebecca A.] Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 283 BP S108 EP S108 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400282 ER PT J AU Lai, CP Mardini, O Maguire, CA Tannous, BA Breakefield, XO AF Lai, Charles P. Mardini, Osama Maguire, Casey A. Tannous, Bakhos A. Breakefield, Xandra O. TI Non-Invasive In Vivo Imaging, Biodistribution and Clearance Analyses of Intravenously Administered Extracellular Vesicles SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Lai, Charles P.; Mardini, Osama; Maguire, Casey A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Charlestown, MA USA. [Lai, Charles P.; Mardini, Osama; Maguire, Casey A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Neurosci Program, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2013 VL 21 SU 1 MA 103 BP S42 EP S43 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400104 ER PT J AU Maguire, CA Crommentuijn, MHW Mu, DK Hudry, E Serrano-Pozo, A Hyman, B Tannous, BA AF Maguire, Casey A. Crommentuijn, Matheus H. W. Mu, Dakai Hudry, Eloise Serrano-Pozo, Alberto Hyman, Bradley Tannous, Bakhos A. TI Mouse Gender Influences Brain Expression of a Reporter Gene by Intravascularly-Administered AAV9 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Maguire, Casey A.; Crommentuijn, Matheus H. W.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Charlestown, MA USA. [Maguire, Casey A.; Mu, Dakai; Hudry, Eloise; Serrano-Pozo, Alberto; Hyman, Bradley; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Crommentuijn, Matheus H. W.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp,Dept Neurosurg, Amterstam, Netherlands. [Mu, Dakai; Hudry, Eloise; Serrano-Pozo, Alberto; Hyman, Bradley] Massachusetts Gen Hosp, Charlestown, MA USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 540 BP S208 EP S208 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400539 ER PT J AU Taherian, M Prabhakar, S Fulci, G Sena-Esteves, M Breakefield, XO Brenner, GJ AF Taherian, Mehran Prabhakar, Shilpa Fulci, Giulia Sena-Esteves, Miguel Breakefield, Xandra O. Brenner, Gary J. TI Mechanisms of Caspase-1 Mediated Schwannoma Regression SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Taherian, Mehran; Prabhakar, Shilpa; Fulci, Giulia; Breakefield, Xandra O.; Brenner, Gary J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sena-Esteves, Miguel] U Mass Med Sch, Worcester, MA USA. [Prabhakar, Shilpa; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 286 BP S109 EP S109 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400285 ER PT J AU Tsai, SQ Reyon, D Khayter, C Joung, JK AF Tsai, Shengdar Q. Reyon, Deepak Khayter, Cyd Joung, J. Keith TI Precise Modification of Human Genes Directed by Single-Stranded DNA Oligonucleotides and TALENs SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Tsai, Shengdar Q.; Reyon, Deepak; Khayter, Cyd; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA USA. [Tsai, Shengdar Q.; Reyon, Deepak; Khayter, Cyd; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Tsai, Shengdar Q.; Reyon, Deepak; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2013 VL 21 SU 1 MA 490 BP S189 EP S189 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400489 ER PT J AU Turunen, HT Velez, MVL Shelke, R Xiao, R Bennett, J Vandenberghe, LH AF Turunen, Heikki T. Velez, Maria Victoria Luna Shelke, Rajani Xiao, Ru Bennett, Jean Vandenberghe, Luk H. TI Comparing Dual AAV Vector Strategy Efficiencies for Gene Therapy In Vitro and In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Turunen, Heikki T.; Shelke, Rajani; Xiao, Ru; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Velez, Maria Victoria Luna] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. [Velez, Maria Victoria Luna; Bennett, Jean] Univ Penn, Sch Med, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2013 VL 21 SU 1 MA 330 BP S127 EP S127 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400329 ER PT J AU van Rijn, S Nilsson, J Noske, DP Vandertop, WP Tannous, BA Wurdinger, T AF van Rijn, Sjoerd Nilsson, Jonas Noske, David P. Vandertop, W. Peter Tannous, Bakhos A. Wuerdinger, Thomas TI Transcription Factor Activity Analysis Using a Functional Multiplex Gaussia Luciferase-Based Reporter Assay SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [van Rijn, Sjoerd; Nilsson, Jonas; Noske, David P.; Vandertop, W. Peter; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Amsterdam, Netherlands. [Nilsson, Jonas] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Tannous, Bakhos A.; Wuerdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2013 VL 21 SU 1 MA 321 BP S123 EP S124 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400320 ER PT J AU Charvet, L Serafin, D Vazquez, K Ackerson, J Braaten, E Brown, T O'Donnell, E Parrish, J Preston, T Zaccariello, M Belman, A Casper, C Chitnis, T Gorman, M Julian, L Ness, J Patterson, M Rodriguez, M Waubant, E Weinstock-Guttman, B Yeh, A Benedict, R Krupp, L AF Charvet, L. Serafin, D. Vazquez, K. Ackerson, J. Braaten, E. Brown, T. O'Donnell, E. Parrish, J. Preston, T. Zaccariello, M. Belman, A. Casper, C. Chitnis, T. Gorman, M. Julian, L. Ness, J. Patterson, M. Rodriguez, M. Waubant, E. Weinstock-Guttman, B. Yeh, A. Benedict, R. Krupp, L. TI Longitudinal Evaluation of Cognitive Impairment in Pediatric MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 2nd Conference of the International-MS-Cognition-Society (IMSCOGS ) CY JUN 28-29, 2013 CL Zurich, SWITZERLAND SP Int MS Cognit Soc C1 [Charvet, L.; Serafin, D.; Vazquez, K.; Preston, T.; Belman, A.; Krupp, L.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Ackerson, J.; Ness, J.] Univ Alabama, Tuscaloosa, AL USA. [Parrish, J.; Weinstock-Guttman, B.; Benedict, R.] SUNY Buffalo, Buffalo, NY 14260 USA. [Braaten, E.; O'Donnell, E.; Chitnis, T.; Gorman, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, T.; Zaccariello, M.; Patterson, M.; Rodriguez, M.] Mayo Clin, Rochester, MN USA. [Casper, C.] Univ Utah, Salt Lake City, UT USA. [Julian, L.; Waubant, E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yeh, A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD JUN PY 2013 VL 19 IS 7 MA 8 BP 972 EP 972 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 152YK UT WOS:000319567900033 ER PT J AU Adamala, K Szostak, JW AF Adamala, Katarzyna Szostak, Jack W. TI Competition between model protocells driven by an encapsulated catalyst SO NATURE CHEMISTRY LA English DT Article ID SELF-REPRODUCTION; VESICLES; LIFE; MEMBRANES; CELL; CHEMISTRY; LIPOSOMES; ORIGIN AB The advent of Darwinian evolution required the emergence of molecular mechanisms for the heritable variation of fitness. One model for such a system involves competing protocell populations, each consisting of a replicating genetic polymer within a replicating vesicle. In this model, each genetic polymer imparts a selective advantage to its protocell by, for example, coding for a catalyst that generates a useful metabolite. Here, we report a partial model of such nascent evolutionary traits in a system that consists of fatty-acid vesicles containing a dipeptide catalyst, which catalyses the formation of a second dipeptide. The newly formed dipeptide binds to vesicle membranes, which imparts enhanced affinity for fatty acids and thus promotes vesicle growth. The catalysed dipeptide synthesis proceeds with higher efficiency in vesicles than in free solution, which further enhances fitness. Our observations suggest that, in a replicating protocell with an RNA genome, ribozyme-catalysed peptide synthesis might have been sufficient to initiate Darwinian evolution. C1 [Adamala, Katarzyna; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Adamala, Katarzyna; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Adamala, Katarzyna] Univ Roma Tre, Dipartimento Biol, Rome, Italy. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Adamala, Kate/0000-0003-1066-7207 FU National Aeronautics and Space Administration Exobiology [NNX07AJ09G] FX J.W.S. is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by National Aeronautics and Space Administration Exobiology grant NNX07AJ09G. We thank A. Engelhart, C. Hentrich, I. Budin and R. Wieczorek for discussions and help with manuscript preparation. NR 24 TC 52 Z9 58 U1 8 U2 101 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1755-4330 J9 NAT CHEM JI Nat. Chem. PD JUN PY 2013 VL 5 IS 6 BP 495 EP 501 DI 10.1038/NCHEM.1650 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 150QC UT WOS:000319404900012 PM 23695631 ER PT J AU Lonsdale, J Thomas, J Salvatore, M Phillips, R Lo, E Shad, S Hasz, R Walters, G Garcia, F Young, N Foster, B Moser, M Karasik, E Gillard, B Ramsey, K Sullivan, S Bridge, J Magazine, H Syron, J Fleming, J Siminoff, L Traino, H Mosavel, M Barker, L Jewell, S Rohrer, D Maxim, D Filkins, D Harbach, P Cortadillo, E Berghuis, B Turner, L Hudson, E Feenstra, K Sobin, L Robb, J Branton, P Korzeniewski, G Shive, C Tabor, D Qi, LQ Groch, K Nampally, S Buia, S Zimmerman, A Smith, A Burges, R Robinson, K Valentino, K Bradbury, D Cosentino, M Diaz-Mayoral, N Kennedy, M Engel, T Williams, P Erickson, K Ardlie, K Winckler, W Getz, G DeLuca, D MacArthur, D Kellis, M Thomson, A Young, T Gelfand, E Donovan, M Meng, Y Grant, G Mash, D Marcus, Y Basile, M Liu, J Zhu, J Tu, ZD Cox, NJ Nicolae, DL Gamazon, ER Im, HK Konkashbaev, A Pritchard, J Stevens, M Flutre, T Wen, XQ Dermitzakis, ET Lappalainen, T Guigo, R Monlong, J Sammeth, M Koller, D Battle, A Mostafavi, S McCarthy, M Rivas, M Maller, J Rusyn, I Nobel, A Wright, F Shabalin, A Feolo, M Sharopova, N Sturcke, A Paschal, J Anderson, JM Wilder, EL Derr, LK Green, ED Struewing, JP Temple, G Volpi, S Boyer, JT Thomson, EJ Guyer, MS Ng, C Abdallah, A Colantuoni, D Insel, TR Koester, SE Little, AR Bender, PK Lehner, T Yao, Y Compton, CC Vaught, JB Sawyer, S Lockhart, NC Demchok, J Moore, HF AF Lonsdale, John Thomas, Jeffrey Salvatore, Mike Phillips, Rebecca Lo, Edmund Shad, Saboor Hasz, Richard Walters, Gary Garcia, Fernando Young, Nancy Foster, Barbara Moser, Mike Karasik, Ellen Gillard, Bryan Ramsey, Kimberley Sullivan, Susan Bridge, Jason Magazine, Harold Syron, John Fleming, Johnelle Siminoff, Laura Traino, Heather Mosavel, Maghboeba Barker, Laura Jewell, Scott Rohrer, Dan Maxim, Dan Filkins, Dana Harbach, Philip Cortadillo, Eddie Berghuis, Bree Turner, Lisa Hudson, Eric Feenstra, Kristin Sobin, Leslie Robb, James Branton, Phillip Korzeniewski, Greg Shive, Charles Tabor, David Qi, Liqun Groch, Kevin Nampally, Sreenath Buia, Steve Zimmerman, Angela Smith, Anna Burges, Robin Robinson, Karna Valentino, Kim Bradbury, Deborah Cosentino, Mark Diaz-Mayoral, Norma Kennedy, Mary Engel, Theresa Williams, Penelope Erickson, Kenyon Ardlie, Kristin Winckler, Wendy Getz, Gad DeLuca, David MacArthur, Daniel Kellis, Manolis Thomson, Alexander Young, Taylor Gelfand, Ellen Donovan, Molly Meng, Yan Grant, George Mash, Deborah Marcus, Yvonne Basile, Margaret Liu, Jun Zhu, Jun Tu, Zhidong Cox, Nancy J. Nicolae, Dan L. Gamazon, Eric R. Im, Hae Kyung Konkashbaev, Anuar Pritchard, Jonathan Stevens, Matthew Flutre, Timothee Wen, Xiaoquan Dermitzakis, Emmanouil T. Lappalainen, Tuuli Guigo, Roderic Monlong, Jean Sammeth, Michael Koller, Daphne Battle, Alexis Mostafavi, Sara McCarthy, Mark Rivas, Manual Maller, Julian Rusyn, Ivan Nobel, Andrew Wright, Fred Shabalin, Andrey Feolo, Mike Sharopova, Nataliya Sturcke, Anne Paschal, Justin Anderson, James M. Wilder, Elizabeth L. Derr, Leslie K. Green, Eric D. Struewing, Jeffery P. Temple, Gary Volpi, Simona Boyer, Joy T. Thomson, Elizabeth J. Guyer, Mark S. Cathy Ng Abdallah, Assya Colantuoni, Deborah Insel, Thomas R. Koester, Susan E. Little, A. Roger Bender, Patrick K. Lehner, Thomas Yao, Yin Compton, Carolyn C. Vaught, Jimmie B. Sawyer, Sherilyn Lockhart, Nicole C. Demchok, Joanne Moore, Helen F. TI The Genotype-Tissue Expression (GTEx) project SO NATURE GENETICS LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; DISEASE AB Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues. C1 [Lonsdale, John; Thomas, Jeffrey; Salvatore, Mike; Phillips, Rebecca; Lo, Edmund; Shad, Saboor] Natl Dis Res Interchange, Philadelphia, PA USA. [Hasz, Richard] Gift Life Donor Program, Philadelphia, PA USA. [Walters, Gary] LifeNet Hlth, Virginia Beach, VA USA. [Garcia, Fernando] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Young, Nancy] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Foster, Barbara; Moser, Mike; Karasik, Ellen; Gillard, Bryan; Ramsey, Kimberley] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Sullivan, Susan; Bridge, Jason] Upstate New York Transplant Serv, Buffalo, NY USA. [Magazine, Harold; Syron, John; Fleming, Johnelle] Sci Care Inc, Phoenix, AZ USA. [Siminoff, Laura; Traino, Heather; Mosavel, Maghboeba; Barker, Laura] Virginia Commonwealth Univ, Richmond, VA USA. [Jewell, Scott; Rohrer, Dan; Maxim, Dan; Filkins, Dana; Harbach, Philip; Cortadillo, Eddie; Berghuis, Bree; Turner, Lisa; Hudson, Eric; Feenstra, Kristin] Van Andel Inst, Grand Rapids, MI USA. [Sobin, Leslie; Robb, James; Branton, Phillip; Korzeniewski, Greg; Shive, Charles; Tabor, David; Qi, Liqun; Groch, Kevin; Nampally, Sreenath; Buia, Steve; Zimmerman, Angela; Smith, Anna; Burges, Robin; Robinson, Karna; Valentino, Kim; Bradbury, Deborah; Cosentino, Mark; Diaz-Mayoral, Norma; Kennedy, Mary; Engel, Theresa; Williams, Penelope] SAIC Frederick Inc, Frederick, MD USA. [Erickson, Kenyon] Sapient Govt Serv, Arlington, VA USA. [Ardlie, Kristin; Winckler, Wendy; Getz, Gad; DeLuca, David; MacArthur, Daniel; Kellis, Manolis; Thomson, Alexander; Young, Taylor; Gelfand, Ellen; Donovan, Molly; Meng, Yan; Grant, George] Broad Inst Harvard & MIT, Cambridge, MA USA. [Getz, Gad; MacArthur, Daniel] Massachusetts Gen Hosp, Res Ctr, Boston, MA 02114 USA. [Kellis, Manolis] MIT, Cambridge, MA 02139 USA. [Mash, Deborah; Marcus, Yvonne; Basile, Margaret] Univ Miami, Sch Med, Miami, FL USA. [Liu, Jun] Harvard Univ, Boston, MA 02115 USA. [Zhu, Jun; Tu, Zhidong] Mt Sinai Sch Med, New York, NY USA. [Cox, Nancy J.; Nicolae, Dan L.; Gamazon, Eric R.; Im, Hae Kyung; Konkashbaev, Anuar; Pritchard, Jonathan; Stevens, Matthew; Flutre, Timothee; Wen, Xiaoquan] Univ Chicago, Chicago, IL 60637 USA. [Pritchard, Jonathan] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Univ Geneva, Geneva, Switzerland. [Guigo, Roderic; Monlong, Jean; Sammeth, Michael] Ctr Genom Regulat, Barcelona, Spain. [Koller, Daphne; Battle, Alexis; Mostafavi, Sara] Stanford Univ, Palo Alto, CA 94304 USA. [McCarthy, Mark; Rivas, Manual; Maller, Julian] Univ Oxford, Oxford, England. [Rusyn, Ivan; Nobel, Andrew; Wright, Fred; Shabalin, Andrey] Univ N Carolina, Chapel Hill, NC USA. [Feolo, Mike; Sharopova, Nataliya; Sturcke, Anne; Paschal, Justin; Anderson, James M.; Wilder, Elizabeth L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Derr, Leslie K.] NIH, Div Program Coordinat Planning & Strateg Initiat, Off Strateg Coordinat Common Fund, Off Director, Bethesda, MD 20892 USA. [Green, Eric D.; Struewing, Jeffery P.; Temple, Gary; Volpi, Simona; Boyer, Joy T.; Thomson, Elizabeth J.; Guyer, Mark S.; Cathy Ng; Abdallah, Assya; Colantuoni, Deborah] NHGRI, Bethesda, MD 20892 USA. [Insel, Thomas R.; Koester, Susan E.; Little, A. Roger; Bender, Patrick K.; Lehner, Thomas; Yao, Yin] NIMH, Bethesda, MD 20892 USA. [Compton, Carolyn C.; Vaught, Jimmie B.; Sawyer, Sherilyn; Lockhart, Nicole C.; Demchok, Joanne; Moore, Helen F.] NCI, Bethesda, MD 20892 USA. RP Getz, G (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA. EM winckler@broadinstitute.org; gadgetz@broadinstitute.org; struewij@mail.nih.gov RI Sammeth, Michael/C-1157-2014; Little, A/O-6191-2014; Guigo, Roderic/D-1303-2010; Rusyn, Ivan/S-2426-2016; Struewing, Jeffery/I-7502-2013; OI Sammeth, Michael/0000-0002-6528-9883; Little, A/0000-0001-6831-0177; Guigo, Roderic/0000-0002-5738-4477; Maller, Julian/0000-0002-1565-9559; Gamazon, Eric/0000-0003-4204-8734; Struewing, Jeffery/0000-0002-4848-3334; Shabalin, Andrey/0000-0003-0309-6821; Lappalainen, Tuuli/0000-0002-7746-8109; Monlong, Jean/0000-0002-9737-5516; Wen, Xiaoquan/0000-0001-8990-2737 NR 18 TC 420 Z9 421 U1 8 U2 44 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2013 VL 45 IS 6 BP 580 EP 585 DI 10.1038/ng.2653 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 152XA UT WOS:000319563900002 ER PT J AU den Hoed, M Eijgelsheim, M Esko, T Brundel, BJJM Peal, DS Evans, DM Nolte, IM Segre, AV Holm, H Handsaker, RE Westra, HJ Johnson, T Isaacs, A Yang, J Lundby, A Zhao, JH Kim, YJ Go, MJ Almgren, P Bochud, M Boucher, G Cornelis, MC Gudbjartsson, D Hadley, D van der Harst, P Hayward, C den Heijer, M Igl, W Jackson, AU Kutalik, Z Luan, J Kemp, JP Kristiansson, K Ladenvall, C Lorentzon, M Montasser, ME Njajou, OT O'Reilly, PF Padmanabhan, S Pourcain, BS Rankinen, T Salo, P Tanaka, T Timpson, NJ Vitart, V Waite, L Wheeler, W Zhang, WH Draisma, HHM Feitosa, MF Kerr, KF Lind, PA Mihailov, E Onland-Moret, NC Song, C Weedon, MN Xie, WJ Yengo, L Absher, D Albert, CM Alonso, A Arking, DE de Bakker, PIW Balkau, B Barlassina, C Benaglio, P Bis, JC Bouatia-Naji, N Brage, S Chanock, SJ Chines, PS Chung, M Darbar, D Dina, C Dorr, M Elliott, P Felix, SB Fischer, K Fuchsberger, C de Geus, EJC Goyette, P Gudnason, V Harris, TB Hartikainen, AL Havulinna, AS Heckbert, SR Hicks, AA Hofman, A Holewijn, S Hoogstra-Berends, F Hottenga, JJ Jensen, MK Johansson, A Junttila, J Kaab, S Kanon, B Ketkar, S Khaw, KT Knowles, JW Kooner, AS Kors, JA Kumari, M Milani, L Laiho, P Lakatta, EG Langenberg, C Leusink, M Liu, YM Luben, RN Lunetta, KL Lynch, SN Markus, MRP Marques-Vidal, P Leach, IM McArdle, WL McCarroll, SA Medland, SE Miller, KA Montgomery, GW Morrison, AC Muller-Nurasyid, M Navarro, P Nelis, M O'Connell, JR O'Donnell, CJ Ong, KK Newman, AB Peters, A Polasek, O Pouta, A Pramstaller, PP Psaty, BM Rao, DC Ring, SM Rossin, EJ Rudan, D Sanna, S Scott, RA Sehmi, JS Sharp, S Shin, JT Singleton, AB Smith, AV Soranzo, N Spector, TD Stewart, C Stringham, HM Tarasov, KV Uitterlinden, AG Vandenput, L Hwang, SJ Whitfield, JB Wijmenga, C Wild, SH Willemsen, G Wilson, JF Witteman, JCM Wong, A Wong, QN Jamshidi, Y Zitting, P Boer, JMA Boomsma, DI Borecki, IB van Duijn, CM Ekelund, U Forouhi, NG Froguel, P Hingorani, A Ingelsson, E Kivimaki, M Kronmal, RA Kuh, D Lind, L Martin, NG Oostra, BA Pedersen, NL Quertermous, T Rotter, JI van der Schouw, YT Verschuren, WMM Walker, M Albanes, D Arnar, DO Assimes, TL Bandinelli, S Boehnke, M de Boer, RA Bouchard, C Caulfield, WLM Chambers, JC Curhan, G Cusi, D Eriksson, J Ferrucci, L van Gilst, WH Glorioso, N de Graaf, J Groop, L Gyllensten, U Hsueh, WC Hu, FB Huikuri, HV Hunter, DJ Iribarren, C Isomaa, B Jarvelin, MR Jula, A Kahonen, M Kiemeney, LA van der Klauw, MM Kooner, JS Kraft, P Iacoviello, L Lehtimaki, T Lokki, MLL Mitchell, BD Navis, G Nieminen, MS Ohlsson, C Poulter, NR Qi, L Raitakari, OT Rimm, EB Rioux, JD Rizzi, F Rudan, I Salomaa, V Sever, PS Shields, DC Shuldiner, AR Sinisalo, J Stanton, AV Stolk, RP Strachan, DP Tardif, JC Thorsteinsdottir, U Tuomilehto, J van Veldhuisen, DJ Virtamo, J Viikari, J Vollenweider, P Waeber, G Widen, E Cho, YS Olsen, JV Visscher, PM Willer, C Franke, L Erdmann, J Thompson, JR Pfeufer, A Sotoodehnia, N Newton-Cheh, C Ellinor, PT Stricker, BHC Metspalu, A Perola, M Beckmann, JS Smith, GD Stefansson, K Wareham, NJ Munroe, PB Sibon, OCM Milan, DJ Snieder, H Samani, NJ Loos, RJF AF den Hoed, Marcel Eijgelsheim, Mark Esko, Tonu Brundel, Bianca J. J. M. Peal, David S. Evans, David M. Nolte, Ilja M. Segre, Ayellet V. Holm, Hilma Handsaker, Robert E. Westra, Harm-Jan Johnson, Toby Isaacs, Aaron Yang, Jian Lundby, Alicia Zhao, Jing Hua Kim, Young Jin Go, Min Jin Almgren, Peter Bochud, Murielle Boucher, Gabrielle Cornelis, Marilyn C. Gudbjartsson, Daniel Hadley, David van der Harst, Pim Hayward, Caroline den Heijer, Martin Igl, Wilmar Jackson, Anne U. Kutalik, Zoltan Luan, Jian'an Kemp, John P. Kristiansson, Kati Ladenvall, Claes Lorentzon, Mattias Montasser, May E. Njajou, Omer T. O'Reilly, Paul F. Padmanabhan, Sandosh Pourcain, Beate St. Rankinen, Tuomo Salo, Perttu Tanaka, Toshiko Timpson, Nicholas J. Vitart, Veronique Waite, Lindsay Wheeler, William Zhang, Weihua Draisma, Harmen H. M. Feitosa, Mary F. Kerr, Kathleen F. Lind, Penelope A. Mihailov, Evelin Onland-Moret, N. Charlotte Song, Ci Weedon, Michael N. Xie, Weijia Yengo, Loic Absher, Devin Albert, Christine M. Alonso, Alvaro Arking, Dan E. de Bakker, Paul I. W. Balkau, Beverley Barlassina, Cristina Benaglio, Paola Bis, Joshua C. Bouatia-Naji, Nabila Brage, Soren Chanock, Stephen J. Chines, Peter S. Chung, Mina Darbar, Dawood Dina, Christian Doerr, Marcus Elliott, Paul Felix, Stephan B. Fischer, Krista Fuchsberger, Christian de Geus, Eco J. C. Goyette, Philippe Gudnason, Vilmundur Harris, Tamara B. Hartikainen, Anna-Liisa Havulinna, Aki S. Heckbert, Susan R. Hicks, Andrew A. Hofman, Albert Holewijn, Suzanne Hoogstra-Berends, Femke Hottenga, Jouke-Jan Jensen, Majken K. Johansson, Asa Junttila, Juhani Kaeaeb, Stefan Kanon, Bart Ketkar, Shamika Khaw, Kay-Tee Knowles, Joshua W. Kooner, Angrad S. Kors, Jan A. Kumari, Meena Milani, Lili Laiho, Paeivi Lakatta, Edward G. Langenberg, Claudia Leusink, Maarten Liu, Yongmei Luben, Robert N. Lunetta, Kathryn L. Lynch, Stacey N. Markus, Marcello R. P. Marques-Vidal, Pedro Leach, Irene Mateo McArdle, Wendy L. McCarroll, Steven A. Medland, Sarah E. Miller, Kathryn A. Montgomery, Grant W. Morrison, Alanna C. Mueller-Nurasyid, Martina Navarro, Pau Nelis, Mari O'Connell, Jeffrey R. O'Donnell, Christopher J. Ong, Ken K. Newman, Anne B. Peters, Annette Polasek, Ozren Pouta, Anneli Pramstaller, Peter P. Psaty, Bruce M. Rao, Dabeeru C. Ring, Susan M. Rossin, Elizabeth J. Rudan, Diana Sanna, Serena Scott, Robert A. Sehmi, Jaban S. Sharp, Stephen Shin, Jordan T. Singleton, Andrew B. Smith, Albert V. Soranzo, Nicole Spector, Tim D. Stewart, Chip Stringham, Heather M. Tarasov, Kirill V. Uitterlinden, Andre G. Vandenput, Liesbeth Hwang, Shih-Jen Whitfield, John B. Wijmenga, Cisca Wild, Sarah H. Willemsen, Gonneke Wilson, James F. Witteman, Jacqueline C. M. Wong, Andrew Wong, Quenna Jamshidi, Yalda Zitting, Paavo Boer, Jolanda M. A. Boomsma, Dorret I. Borecki, Ingrid B. van Duijn, Cornelia M. Ekelund, Ulf Forouhi, Nita G. Froguel, Philippe Hingorani, Aroon Ingelsson, Erik Kivimaki, Mika Kronmal, Richard A. Kuh, Diana Lind, Lars Martin, Nicholas G. Oostra, Ben A. Pedersen, Nancy L. Quertermous, Thomas Rotter, Jerome I. van der Schouw, Yvonne T. Verschuren, W. M. Monique Walker, Mark Albanes, Demetrius Arnar, David O. Assimes, Themistocles L. Bandinelli, Stefania Boehnke, Michael de Boer, Rudolf A. Bouchard, Claude Caulfield, W. L. Mark Chambers, John C. Curhan, Gary Cusi, Daniele Eriksson, Johan Ferrucci, Luigi van Gilst, Wiek H. Glorioso, Nicola de Graaf, Jacqueline Groop, Leif Gyllensten, Ulf Hsueh, Wen-Chi Hu, Frank B. Huikuri, Heikki V. Hunter, David J. Iribarren, Carlos Isomaa, Bo Jarvelin, Marjo-Riitta Jula, Antti Kahonen, Mika Kiemeney, Lambertus A. van der Klauw, Melanie M. Kooner, Jaspal S. Kraft, Peter Iacoviello, Licia Lehtimaki, Terho Lokki, Marja-Liisa L. Mitchell, Braxton D. Navis, Gerjan Nieminen, Markku S. Ohlsson, Claes Poulter, Neil R. Qi, Lu Raitakari, Olli T. Rimm, Eric B. Rioux, John D. Rizzi, Federica Rudan, Igor Salomaa, Veikko Sever, Peter S. Shields, Denis C. Shuldiner, Alan R. Sinisalo, Juha Stanton, Alice V. Stolk, Ronald P. Strachan, David P. Tardif, Jean-Claude Thorsteinsdottir, Unnur Tuomilehto, Jaako van Veldhuisen, Dirk J. Virtamo, Jarmo Viikari, Jorma Vollenweider, Peter Waeber, Gerard Widen, Elisabeth Cho, Yoon Shin Olsen, Jesper V. Visscher, Peter M. Willer, Cristen Franke, Lude Erdmann, Jeanette Thompson, John R. Pfeufer, Arne Sotoodehnia, Nona Newton-Cheh, Christopher Ellinor, Patrick T. Stricker, Bruno H. Ch Metspalu, Andres Perola, Markus Beckmann, Jacques S. Smith, George Davey Stefansson, Kari Wareham, Nicholas J. Munroe, Patricia B. Sibon, Ody C. M. Milan, David J. Snieder, Harold Samani, Nilesh J. Loos, Ruth J. F. CA Global BPgen Consortium CARDIoGRAM Consortium PR GWGWAS Consortium QRS GWGWAS Consortium QT-IGCGC Consortium CHARGE-AF Consortium TI Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; SUSCEPTIBILITY LOCI; ATRIAL-FIBRILLATION; QRS DURATION; QT INTERVAL; PR INTERVAL; DISEASE; DROSOPHILA; LIBRARY AB Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. C1 [den Hoed, Marcel; Zhao, Jing Hua; Luan, Jian'an; Brage, Soren; Langenberg, Claudia; Ong, Ken K.; Scott, Robert A.; Sharp, Stephen; Ekelund, Ulf; Forouhi, Nita G.; Wareham, Nicholas J.; Loos, Ruth J. 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[Shields, Denis C.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland. [Shields, Denis C.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 2, Ireland. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Stanton, Alice V.] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Tuomilehto, Jaako] Natl Inst Hlth & Welf, Diabet Unit, Helsinki, Finland. Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. Hosp Univ La Paz, Grp RD06 0014 0015, Red RECAVA, Madrid, Spain. [Tuomilehto, Jaako] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland. [Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea. [Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Willer, Cristen] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Franke, Lude] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol Sci, London, England. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Gen, D-23538 Lubeck, Germany. [Erdmann, Jeanette] DZHK, Lubeck, Germany. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Pfeufer, Arne] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Munich, Germany. [Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany. [Sotoodehnia, Nona] Univ Washington, Sch Med, Div Cardiol, Dept Med, Seattle, WA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovacular Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands. [Beckmann, Jacques S.] CHUV Univ Hosp, Serv Med Genet, Lausanne, Switzerland. [Milan, David J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, NIHR Leicester Biomed Res Unit Cardiovasc, Leicester, Leics, England. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA. RP Loos, RJF (reprint author), Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England. EM ruth.loos@mssm.edu RI Wijmenga, Cisca/D-2173-2009; Lundby, Alicia/H-3322-2013; Evans, David/H-6325-2013; Lind, Penelope/B-2553-2009; Colaus, PsyColaus/K-6607-2013; Stanton, Alice/F-4697-2012; de Bakker, Paul/B-8730-2009; van der Klauw, Melanie/A-2138-2014; Kiemeney, Lambertus/D-3357-2009; Singleton, Andrew/C-3010-2009; Pfeufer, Arne/B-6634-2013; van Veldhuisen, Dirk Jan/E-8967-2014; Erdmann, Jeanette/P-7513-2014; Marques-Vidal, Pedro/C-9449-2009; Franke, Lude/P-7036-2016; Fox, Laura /C-6249-2016; Padmanabhan, Sandosh/S-3963-2016; Wong, Andrew/M-8899-2016; Kerr, Kathleen/A-2893-2013; Davey Smith, George/A-7407-2013; Beckmann, Jacques S /A-9772-2008; Yengo, Loic/D-2692-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Graaf, J./H-8038-2014; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Alonso, Alvaro/A-4917-2010; Johansson, Asa/G-5270-2011; Peters, Annette/A-6117-2011; Bouchard, Claude/A-7637-2009; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015; Yang, Jian/A-5852-2010; Bochud, Murielle/A-3981-2010; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; van der Schouw, Yvonne/F-8327-2014; Pramstaller, Peter/C-2357-2008; Newman, Anne/C-6408-2013; Medland, Sarah/C-7630-2013; Albanes, Demetrius/B-9749-2015; Darbar, Dawood/C-9079-2015; Dina, Christian/D-3535-2015; Milani, Lili/C-8759-2011; Rioux, John/A-9599-2015; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason, Vilmundur/K-6885-2015 OI de Bakker, Paul/0000-0001-7735-7858; van der Klauw, Melanie/0000-0001-7178-009X; Kiemeney, Lambertus/0000-0002-2368-1326; Markus, Marcello Ricardo Paulista/0000-0002-6234-4955; Navarro, Pau/0000-0001-5576-8584; Iacoviello, Licia/0000-0003-0514-5885; Visscher, Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Kemp, John/0000-0002-9105-2249; Evans, David/0000-0003-0663-4621; Mitchell, Braxton/0000-0003-4920-4744; Timpson, Nicholas/0000-0002-7141-9189; Sinisalo, Juha/0000-0002-0169-5137; de Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020; Erdmann, Jeanette/0000-0002-4486-6231; Olsen, Jesper/0000-0002-4747-4938; Luben, Robert/0000-0002-5088-6343; Jamshidi, Yalda/0000-0003-0151-6482; Soranzo, Nicole/0000-0003-1095-3852; Wijmenga, Cisca/0000-0002-5635-1614; St Pourcain, Beate/0000-0002-4680-3517; Kumari, Meena/0000-0001-9716-1035; Forouhi, Nita/0000-0002-5041-248X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Vandenput, Liesbeth/0000-0002-1712-6131; Lundby, Alicia/0000-0002-1612-6041; Lind, Penelope/0000-0002-3887-2598; sanna, serena/0000-0002-3768-1749; Marques-Vidal, Pedro/0000-0002-4548-8500; Gudbjartsson, Daniel/0000-0002-5222-9857; Monsalve, Beatriz Elena/0000-0002-5994-866X; Johnson, Toby/0000-0002-5998-3270; Fuchsberger, Christian/0000-0002-5918-8947; Padmanabhan, Sandosh/0000-0003-3869-5808; den Hoed, Marcel/0000-0001-8081-428X; Stanton, Alice/0000-0002-4961-165X; Esko, Tonu/0000-0003-1982-6569; Kristiansson, Kati/0000-0003-4688-107X; Bouatia-Naji, Nabila/0000-0001-5424-2134; Willer, Cristen/0000-0001-5645-4966; Franke, Lude/0000-0002-5159-8802; Wong, Andrew/0000-0003-2079-4779; Davey Smith, George/0000-0002-1407-8314; Beckmann, Jacques S /0000-0002-9741-1900; Yengo, Loic/0000-0002-4272-9305; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Lunetta, Kathryn/0000-0002-9268-810X; Song, Ci/0000-0002-0947-9068; Kivimaki, Mika/0000-0002-4699-5627; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139; Alonso, Alvaro/0000-0002-2225-8323; Johansson, Asa/0000-0002-2915-4498; Rudan, Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845; Yang, Jian/0000-0003-2001-2474; Bochud, Murielle/0000-0002-5727-0218; Hayward, Caroline/0000-0002-9405-9550; van der Schouw, Yvonne/0000-0002-4605-435X; Newman, Anne/0000-0002-0106-1150; Medland, Sarah/0000-0003-1382-380X; Darbar, Dawood/0000-0002-4103-5977; Dina, Christian/0000-0002-7722-7348; Milani, Lili/0000-0002-5323-3102; Rioux, John/0000-0001-7560-8326; Gudnason, Vilmundur/0000-0001-5696-0084 FU British Heart Foundation [PG/12/38/29615]; Chief Scientist Office [CZB/4/710]; Medical Research Council [G0401527, G0600705, G0801056, G1000143, G1002084, G9815508, MC_PC_15018, MC_PC_U127592696, MC_U106179471, MC_U106179472, MC_U106179473, MC_U106188470, MC_U123092720, MC_U127592696, MC_UP_A100_1003, MC_UU_12013/1, MC_UU_12013/3, MC_UU_12013/4]; NCATS NIH HHS [UL1 TR000124]; NHLBI NIH HHS [K24 HL105780, R00 HL094535, R01 HL090620, R01 HL092217, R01 HL105756, R01 HL111314, U19 HL065962]; NIDA NIH HHS [R21 DA026982]; NIDDK NIH HHS [P30 DK020572, P30 DK063491]; NIGMS NIH HHS [T32 GM007753]; Wellcome Trust [092731] NR 47 TC 72 Z9 72 U1 2 U2 67 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2013 VL 45 IS 6 BP 621 EP + DI 10.1038/ng.2610 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 152XA UT WOS:000319563900009 PM 23583979 ER PT J AU Monda, KL Chen, GK Taylor, KC Palmer, C Edwards, TL Lange, LA Ng, MCY Adeyemo, AA Allison, MA Bielak, LF Chen, GJ Graff, M Irvin, MR Rhie, SK Li, G Liu, YM Liu, YF Lu, YC Nalls, MA Sun, YV Wojczynski, MK Yanek, LR Aldrich, MC Ademola, A Amos, CI Bandera, EV Bock, CH Britton, A Broeckel, U Cai, QY Caporaso, NE Carlson, CS Carpten, J Casey, G Chen, WM Chen, F Chen, YDI Chiang, CWK Coetzee, GA Demerath, E Deming-Halverson, SL Driver, RW Dubbert, P Feitosa, MF Feng, Y Freedman, BI Gillanders, EM Gottesman, O Guo, XQ Haritunians, T Harris, T Harris, CC Hennis, AJM Hernandez, DG McNeill, LH Howard, TD Howard, BV Howard, VJ Johnson, KC Kang, SJ Keating, BJ Kolb, S Kuller, LH Kutlar, A Langefeld, CD Lettre, G Lohman, K Lotay, V Lyon, H Manson, JE Maixner, W Meng, YA Monroe, KR Morhason-Bello, I Murphy, AB Mychaleckyj, JC Nadukuru, R Nathanson, KL Nayak, U N'Diaye, A Nemesure, B Wu, SY Leske, MC Neslund-Dudas, C Neuhouser, M Nyante, S Ochs-Balcom, H Ogunniyi, A Ogundiran, TO Ojengbede, O Olopade, OI Palmer, JR Ruiz-Narvaez, EA Palmer, ND Press, MF Rampersaud, E Rasmussen-Torvik, LJ Rodriguez-Gil, JL Salako, B Schadt, EE Schwartz, AG Shriner, DA Siscovick, D Smith, SB Wassertheil-Smoller, S Speliotes, EK Spitz, MR Sucheston, L Taylor, H Tayo, BO Tucker, MA Van Den Berg, DJ Edwards, DRV Wang, Z Wiencke, JK Winkler, TW Witte, JS Wrensch, M Wu, XF Yang, JJ Levin, AM Young, TR Zakai, NA Cushman, M Zanetti, KA Zhao, JH Zhao, W Zheng, YL Zhou, J Ziegler, RG Zmuda, JM Fernandes, JK Gilkeson, GS Kamen, DL Hunt, KJ Spruill, IJ Ambrosone, CB Ambs, S Arnett, DK Atwood, L Becker, DM Berndt, SI Bernstein, L Blot, WJ Borecki, IB Bottinger, EP Bowden, DW Burke, G Chanock, SJ Cooper, RS Ding, JZ Duggan, D Evans, MK Fox, C Garvey, WT Bradfield, JP Hakonarson, H Grant, SFA Hsing, A Chu, L Hu, JJ Huo, DZ Ingles, SA John, EM Jordan, JM Kabagambe, EK Kardia, SLR Kittles, RA Goodman, PJ Klein, EA Kolonel, LN Le Marchand, L Liu, SM McKnight, B Millikan, RC Mosley, TH Padhukasahasram, B Williams, LK Patel, SR Peters, U Pettaway, CA Peyser, PA Psaty, BM Redline, S Rotimi, CN Rybicki, BA Sale, MM Schreiner, PJ Signorello, LB Singleton, AB Stanford, JL Strom, SS Thun, MJ Vitolins, M Zheng, W Moore, JH Williams, SM Ketkar, S Zhu, XF Zonderman, AB Kooperberg, C Papanicolaou, GJ Henderson, BE Reiner, AP Hirschhorn, JN Loos, RJF North, KE Haiman, CA AF Monda, Keri L. Chen, Gary K. Taylor, Kira C. Palmer, Cameron Edwards, Todd L. Lange, Leslie A. Ng, Maggie C. Y. Adeyemo, Adebowale A. Allison, Matthew A. Bielak, Lawrence F. Chen, Guanjie Graff, Mariaelisa Irvin, Marguerite R. Rhie, Suhn K. Li, Guo Liu, Yongmei Liu, Youfang Lu, Yingchang Nalls, Michael A. Sun, Yan V. Wojczynski, Mary K. Yanek, Lisa R. Aldrich, Melinda C. Ademola, Adeyinka Amos, Christopher I. Bandera, Elisa V. Bock, Cathryn H. Britton, Angela Broeckel, Ulrich Cai, Quiyin Caporaso, Neil E. Carlson, Chris S. Carpten, John Casey, Graham Chen, Wei-Min Chen, Fang Chen, Yii-Der I. Chiang, Charleston W. K. Coetzee, Gerhard A. Demerath, Ellen Deming-Halverson, Sandra L. Driver, Ryan W. Dubbert, Patricia Feitosa, Mary F. Feng, Ye Freedman, Barry I. Gillanders, Elizabeth M. Gottesman, Omri Guo, Xiuqing Haritunians, Talin Harris, Tamara Harris, Curtis C. Hennis, Anselm J. M. Hernandez, Dena G. McNeill, Lorna H. Howard, Timothy D. Howard, Barbara V. Howard, Virginia J. Johnson, Karen C. Kang, Sun J. Keating, Brendan J. Kolb, Suzanne Kuller, Lewis H. Kutlar, Abdullah Langefeld, Carl D. Lettre, Guillaume Lohman, Kurt Lotay, Vaneet Lyon, Helen Manson, Joann E. Maixner, William Meng, Yan A. Monroe, Kristine R. Morhason-Bello, Imran Murphy, Adam B. Mychaleckyj, Josyf C. Nadukuru, Rajiv Nathanson, Katherine L. Nayak, Uma N'Diaye, Amidou Nemesure, Barbara Wu, Suh-Yuh Leske, M. Cristina Neslund-Dudas, Christine Neuhouser, Marian Nyante, Sarah Ochs-Balcom, Heather Ogunniyi, Adesola Ogundiran, Temidayo O. Ojengbede, Oladosu Olopade, Olufunmilayo I. Palmer, Julie R. Ruiz-Narvaez, Edward A. Palmer, Nicholette D. Press, Michael F. Rampersaud, Evandine Rasmussen-Torvik, Laura J. Rodriguez-Gil, Jorge L. Salako, Babatunde Schadt, Eric E. Schwartz, Ann G. Shriner, Daniel A. Siscovick, David Smith, Shad B. Wassertheil-Smoller, Sylvia Speliotes, Elizabeth K. Spitz, Margaret R. Sucheston, Lara Taylor, Herman Tayo, Bamidele O. Tucker, Margaret A. Van Den Berg, David J. Edwards, Digna R. Velez Wang, Zhaoming Wiencke, John K. Winkler, Thomas W. Witte, John S. Wrensch, Margaret Wu, Xifeng Yang, James J. Levin, Albert M. Young, Taylor R. Zakai, Neil A. Cushman, Mary Zanetti, Krista A. Zhao, Jing Hua Zhao, Wei Zheng, Yonglan Zhou, Jie Ziegler, Regina G. Zmuda, Joseph M. Fernandes, Jyotika K. Gilkeson, Gary S. Kamen, Diane L. Hunt, Kelly J. Spruill, Ida J. Ambrosone, Christine B. Ambs, Stefan Arnett, Donna K. Atwood, Larry Becker, Diane M. Berndt, Sonja I. Bernstein, Leslie Blot, William J. Borecki, Ingrid B. Bottinger, Erwin P. Bowden, Donald W. Burke, Gregory Chanock, Stephen J. Cooper, Richard S. Ding, Jingzhong Duggan, David Evans, Michele K. Fox, Caroline Garvey, W. Timothy Bradfield, Jonathan P. Hakonarson, Hakon Grant, Struan F. A. Hsing, Ann Chu, Lisa Hu, Jennifer J. Huo, Dezheng Ingles, Sue A. John, Esther M. Jordan, Joanne M. Kabagambe, Edmond K. Kardia, Sharon L. R. Kittles, Rick A. Goodman, Phyllis J. Klein, Eric A. Kolonel, Laurence N. Le Marchand, Loic Liu, Simin McKnight, Barbara Millikan, Robert C. Mosley, Thomas H. Padhukasahasram, Badri Williams, L. Keoki Patel, Sanjay R. Peters, Ulrike Pettaway, Curtis A. Peyser, Patricia A. Psaty, Bruce M. Redline, Susan Rotimi, Charles N. Rybicki, Benjamin A. Sale, Michele M. Schreiner, Pamela J. Signorello, Lisa B. Singleton, Andrew B. Stanford, Janet L. Strom, Sara S. Thun, Michael J. Vitolins, Mara Zheng, Wei Moore, Jason H. Williams, Scott M. Ketkar, Shamika Zhu, Xiaofeng Zonderman, Alan B. Kooperberg, Charles Papanicolaou, George J. Henderson, Brian E. Reiner, Alex P. Hirschhorn, Joel N. Loos, Ruth J. F. North, Kari E. Haiman, Christopher A. CA NABEC Consortium UKBECEC Consortium BioBank Japan Project AGEN Consortium TI A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTILOCUS GENOTYPE DATA; COMMON VARIANTS; POSITIVE SELECTION; SEQUENCE VARIANTS; HUMAN-POPULATIONS; GENETIC-VARIATION; ADULT OBESITY; FTO GENE; RISK AB Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 x 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 x 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 x 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 x 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations. C1 [Monda, Keri L.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Taylor, Kira C.; Graff, Mariaelisa; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Chen, Gary K.; Rhie, Suhn K.; Casey, Graham; Coetzee, Gerhard A.; Feng, Ye; Monroe, Kristine R.; Van Den Berg, David J.; Ingles, Sue A.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Taylor, Kira C.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. [Palmer, Cameron; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Edwards, Todd L.] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Ctr Human Genet Res, Nashville, TN USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Ng, Maggie C. Y.; Palmer, Nicholette D.; Shriner, Daniel A.; Zhou, Jie; Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA. [Ng, Maggie C. Y.; Howard, Timothy D.; Palmer, Nicholette D.; Bowden, Donald W.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Adeyemo, Adebowale A.; Chen, Guanjie; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Bielak, Lawrence F.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Howard, Virginia J.; Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Rhie, Suhn K.; Casey, Graham; Coetzee, Gerhard A.; Van Den Berg, David J.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Li, Guo; Siscovick, David; McKnight, Barbara; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Liu, Youfang; Jordan, Joanne M.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA. [Lu, Yingchang; Gottesman, Omri; Lotay, Vaneet; Nadukuru, Rajiv; Winkler, Thomas W.; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA. [Nalls, Michael A.; Britton, Angela; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Sun, Yan V.] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Wojczynski, Mary K.; Ademola, Adeyinka; Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Yanek, Lisa R.; Becker, Diane M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Aldrich, Melinda C.; Cai, Quiyin; Deming-Halverson, Sandra L.; Blot, William J.; Kabagambe, Edmond K.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA. [Aldrich, Melinda C.; Cai, Quiyin; Deming-Halverson, Sandra L.; Blot, William J.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37212 USA. [Ademola, Adeyinka; Ogundiran, Temidayo O.] Univ Ibadan, Coll Med, Dept Surg, Ibadan, Nigeria. [Amos, Christopher I.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Amos, Christopher I.] Dartmouth Coll, Geissel Sch Med, Dept Family & Community Med, Hanover, NH 03755 USA. [Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA. [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Broeckel, Ulrich] Med Coll Wisconsin, Dept Pediat, Sect Genom Pediat, Milwaukee, WI 53226 USA. [Caporaso, Neil E.; Tucker, Margaret A.; Ziegler, Regina G.; Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Carlson, Chris S.; Kolb, Suzanne; Peters, Ulrike; Stanford, Janet L.; Kooperberg, Charles; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Carpten, John; Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Chen, Wei-Min; Chen, Fang; Mychaleckyj, Josyf C.; Nayak, Uma] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Chen, Yii-Der I.; Guo, Xiuqing; Haritunians, Talin] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Chiang, Charleston W. K.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA 90033 USA. [Demerath, Ellen; Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Driver, Ryan W.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Dubbert, Patricia] South Cent VA Mental Illness Res & Clin Ctr, Little Rock, AR USA. [Dubbert, Patricia] VA Geriatr Res Educ & Clin Ctr, Little Rock, AR USA. [Dubbert, Patricia] Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Gillanders, Elizabeth M.; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Harris, Tamara; Ketkar, Shamika] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Harris, Curtis C.; Zanetti, Krista A.; Ambs, Stefan; Zhu, Xiaofeng] NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hennis, Anselm J. M.; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Hennis, Anselm J. 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[Kuller, Lewis H.; Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Kutlar, Abdullah] Georgia Hlth Sci Univ, Dept Med, Sickle Cell Ctr, Augusta, GA USA. [Langefeld, Carl D.; Lohman, Kurt] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Lyon, Helen; N'Diaye, Amidou] Childrens Hosp, Div Genet, Program Genom & Endocrinol, Boston, MA 02115 USA. [Lyon, Helen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Maixner, William; Smith, Shad B.] Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC USA. [Morhason-Bello, Imran; Ojengbede, Oladosu] Broad Inst Harvard & MIT, Metab Dis Initiat, Cambridge, MA USA. [Murphy, Adam B.] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. 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[Goodman, Phyllis J.] SWOG Stat Ctr, Southwest Oncol Grp, Seattle, WA USA. [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Padhukasahasram, Badri; Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA. [Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA. [Patel, Sanjay R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Moore, Jason H.; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Inst Quantitat Biomed Sci, Lebanon, NH 03756 USA. [Moore, Jason H.; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Lebanon, NH 03756 USA. [Moore, Jason H.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA. [Ketkar, Shamika] Washington Univ, Human & Stat Genet Program, Div Biol & Biomed Sci, St Louis, MO USA. [Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostatist, Cleveland, OH 44106 USA. [Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Lab Populat Sci, NIH, Baltimore, MD USA. [Papanicolaou, George J.] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA. RP North, KE (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. EM kari_north@unc.edu; haiman@usc.edu RI Singleton, Andrew/C-3010-2009; Liu, Simin/I-3689-2014; Bandera, Elisa/M-4169-2014; Tucker, Margaret/B-4297-2015; Feitosa, Mary/K-8044-2012; OI Zonderman, Alan B/0000-0002-6523-4778; Liu, Simin/0000-0003-2098-3844; Patel, Sanjay/0000-0002-9142-5172; Chiang, Charleston/0000-0002-0668-7865; Allison, Matthew/0000-0003-0777-8272; Bandera, Elisa/0000-0002-8789-2755; Feitosa, Mary/0000-0002-0933-2410; Ruiz-Narvaez, Edward/0000-0002-0339-5824; Palmer, Julie/0000-0002-6534-335X; Nathanson, Katherine/0000-0002-6740-0901; Adeyemo, Adebowale/0000-0002-3105-3231 FU Intramural NIH HHS [Z01 HG200362-01]; NCATS NIH HHS [KL2 TR000446, UL1 TR000055, UL1 TR000124, UL1 TR000150, UL1 TR000439, UL1TR000124]; NCI NIH HHS [CA056678, CA082664, CA092447, CA092579, CA100374, CA127298, CA1326792, CA140388, CA148085, CA164973, CA54281, CA58223, CA63464, CA68485, CA68578, CA73629, CA77305, CA88164, K07 CA136969, P30 CA016086, P30 CA016672, P50 CA058223, P50 CA125183, R01 CA054281, R01 CA055769, R01 CA056678, R01 CA058420, R01 CA063464, R01 CA073629, R01 CA077305, R01 CA082664, R01 CA088164, R01 CA089085, R01 CA092447, R01 CA092579, R01 CA098663, R01 CA100374, R01 CA100598, R01 CA111646, R01 CA114379, R01 CA121197, R01 CA127219, R01 CA133996, R01 CA141712, R01 CA141716, R01 CA142996, RC2 CA148085, RFA CA-06-503, U01 CA127298, U01 CA69417, U10 CA037429, U19 CA148127, UM1 CA164974]; NCRR NIH HHS [1UL1RR024975-01, 2M01RR010284, M01 RR07122, M01RR00080, UL1 RR024156, UL1 RR024975, UL1 RR025005, UL1 RR033176, UL1-RR-024156, UL1-RR-025005, UL1RR025005, UL1RR033176]; NHGRI NIH HHS [HG004726, N01HG25487, R01 HG003054, R01-HG003054, U01 HG004402, U01 HG004424, U01 HG004726, U01 HG004790, U01 HG005152, U01 HG005157, U01 HG006830, U01HG004402, Z01HG200362]; NHLBI NIH HHS [N01-HC-95163, HL 46380, HL087660, HL100245, HL101161, HL54471, HL54472, HL54473, HL54495, HL54496, HL54509, HL54515, N01 HC-55222, N01 HC005187, N01 HC015103, N01 HC045134, N01 HC045204, N01 HC045205, N01 HC048047, N01 HC048048, N01 HC048050, N01 HC065226, N01 HC075150, N01 HC085079, N01 HC095095, N01 HC095159, N01 HC095169, N01 HC095170, N01 HC095171, N01 HC095172, N01-HC-05187, N01-HC-35129, N01-HC-45133, N01-HC-45204, N01-HC-45205, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-65226, N01-HC-75150, 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-85239, N01-HC-95095, N01-HC-95100, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N01-HC-95170, N01-HC-95171, N01-HC-95172, N01HC55222, N02 HL64278, N02-HL-6-4278, N02-HL-64278, R01 HL046380, R01 HL053353, R01 HL055673, R01 HL058625, R01 HL059367, R01 HL059684, R01 HL071025, R01 HL071051, R01 HL071205, R01 HL071250, R01 HL071251, R01 HL071252, R01 HL071258, R01 HL071259, R01 HL074166, R01 HL079055, R01 HL080295, R01 HL085251, R01 HL086694, R01 HL086718, R01 HL087641, R01 HL087652, R01 HL087660, R01 HL087698, R01 HL087700, R01 HL088215, R01 HL101161, R01 HL105756, R01 HL117078, R01 HL55673, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, R01-HL-087700, R01-HL-088215, R01-HL053353, R01-HL074166, R01-HL086718, R01HL086694, R01HL087641, R01HL59367, R37 HL045508, R37-HL045508, RC1 HL100245, SC1 HL095100, U01 HL054471, U01 HL054472, U01 HL054473, U01 HL054495, U01 HL054509, U01 HL054512, U01 HL072518, U01-HL054512]; NIA NIH HHS [1R01AG032098-01A1, AG-023629, AG-027058, AG-20098, N01 AG062101, N01 AG062103, N01 AG062106, R01 AG015928, R01 AG023629, R01 AG027058, Z01-AG000513]; NIAID NIH HHS [R01 AI061774, R01 AI079139]; NIAMS NIH HHS [K23 AR052364, P60 AR062755]; NICHD NIH HHS [N01-HD-3-3175, R01 HD056465, R24 HD050924]; NIDDK NIH HHS [DK063491, K23 DK080145, P30 DK058404, R01 DK053591, R01 DK064695, R01 DK066358, R01 DK075681, R01 DK075787, R01 DK084350, R01 DK087914, R01-DK-075681, R01-DK-8925601, R01-DK075787, R01DK075787, T32 DK007734]; NIEHS NIH HHS [ES007784, ES011126, ES10126, N01HG25487, R01 ES006717, R01 ES011126]; NIGMS NIH HHS [P20 GM103534, S06GM008016-320107, S06GM008016-380111, S06GM08016]; NIMHD NIH HHS [P20 MD006899]; NINDS NIH HHS [U01 NS041588]; NLM NIH HHS [R01 LM010098]; PHS HHS [HHSC268200782096C, HHSN26800625226C, HHSN268200625226C, HHSN268200782096C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201100046C, HHSN26820110005C, HHSN26820110006C, HHSN26820110007C, HHSN26820110008C, HHSN26820110009C, HHSN268201200036C, HHSN271201100004C] NR 48 TC 77 Z9 81 U1 1 U2 43 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2013 VL 45 IS 6 BP 690 EP + DI 10.1038/ng.2608 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 152XA UT WOS:000319563900019 PM 23583978 ER PT J AU Gunta, SS Thadhani, RI Mak, RH AF Gunta, Sujana S. Thadhani, Ravi I. Mak, Robert H. TI The effect of vitamin D status on risk factors for cardiovascular disease SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID CHRONIC KIDNEY-DISEASE; RENIN-ANGIOTENSIN SYSTEM; RANDOMIZED CONTROLLED-TRIAL; LEFT-VENTRICULAR HYPERTROPHY; NUTRITION EXAMINATION SURVEY; PLASMA 25-HYDROXYVITAMIN D; IMMATURE DENDRITIC CELLS; CHRONIC HEART-FAILURE; D-RECEPTOR ACTIVATORS; 3RD NATIONAL-HEALTH AB Vitamin-D-related pathways are implicated in various endocrine, inflammatory and endothelial functions. An estimated 1 billion people in the world have vitamin D deficiency or insufficiency, and undiagnosed vitamin D deficiency is common. Vitamin D deficiency is associated with substantial increases in the incidence of hypertension, hyperlipidaemia, myocardial infarction and stroke, as well as in diseases such as chronic kidney disease and type 2 diabetes. Low vitamin D levels also upregulate the renin-angiotensin-aldosterone system, increase inflammation and cause endothelial dysfunction. However, the role of vitamin D deficiency in cardiovascular morbidity and mortality is an emerging and hotly debated topic. Epidemiological studies suggest an association between low vitamin D levels and risk factors for cardiovascular disease, but a causal relationship has not been established, and clinical trials and meta-analyses have not demonstrated convincing evidence that vitamin D therapy improves cardiovascular outcomes. Some evidence suggests that vitamin D status is a biomarker of lifestyle, since unhealthy and sedentary lifestyles are associated with vitamin D insufficiency or deficiency and are also risk factors for cardiovascular complications. C1 [Gunta, Sujana S.; Mak, Robert H.] Univ Calif San Diego, Div Pediat Nephrol, La Jolla, CA 92093 USA. [Thadhani, Ravi I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med, Boston, MA 02115 USA. RP Mak, RH (reprint author), Univ Calif San Diego, Div Pediat Nephrol, 9500 Gilman Dr,MC 0634, La Jolla, CA 92093 USA. EM romak@ucsd.edu FU NIDDK NIH HHS [R01DK084974, K24DK094872‑01, U01 DK‑3‑012]; NIEHS NIH HHS [P30 ES002109] NR 119 TC 25 Z9 25 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD JUN PY 2013 VL 9 IS 6 BP 337 EP 347 DI 10.1038/nrneph.2013.74 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 152BH UT WOS:000319504000008 PM 23609564 ER PT J AU McKenna, MJ AF McKenna, Michael J. TI In Memory of Saumil Nalin Merchant, M.D. Obituary SO OTOLOGY & NEUROTOLOGY LA English DT Biographical-Item C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP McKenna, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. EM michael_mckenna@meei.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUN PY 2013 VL 34 IS 4 BP 595 EP 596 DI 10.1097/MAO.0b013e318287c9a1 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 146AV UT WOS:000319062100006 ER PT J AU Dilwali, S Lysaght, A Roberts, D Barker, FG McKenna, MJ Stankovic, KM AF Dilwali, Sonam Lysaght, Andrew Roberts, Daniel Barker, Fred G., II McKenna, Michael J. Stankovic, Konstantina M. TI Sporadic Vestibular Schwannomas Associated With Good Hearing Secrete Higher Levels of Fibroblast Growth Factor 2 Than Those Associated With Poor Hearing Irrespective of Tumor Size SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Acoustic neuroma; Cytokine array; FGF2; Hearing loss; Sporadic vestibular schwannoma ID NEUROFIBROMATOSIS TYPE-2 GENE; ACOUSTIC NEUROMAS; HAIR-CELLS; NOISE EXPOSURE; EXPRESSION; PROLIFERATION; INHIBITION; DISEASE; COCHLEA; CANCER AB Hypothesis: We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential. Background: Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions. Methods: Fresh surgical specimens of VS were incubated in sterile PBS at 37 degrees C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition >= 70% and pure-tone average <= 30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group). Results: Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay. Conclusion: This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS. C1 [Dilwali, Sonam; Lysaght, Andrew; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02138 USA. [Dilwali, Sonam; Lysaght, Andrew; Stankovic, Konstantina M.] MIT, Cambridge, MA 02139 USA. [Dilwali, Sonam; Lysaght, Andrew; Roberts, Daniel; McKenna, Michael J.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, Boston, MA 02114 USA. [Roberts, Daniel; McKenna, Michael J.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Barker, Fred G., II] Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. RP Stankovic, KM (reprint author), 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [T32 DC 00038, K08DC010419]; Bertarelli Foundation FX This project was supported by National Institute on Deafness and Other Communication Disorders Grants T32 DC 00038 (S.D. and A.L.) and K08DC010419 (K.M.S.), and the Bertarelli Foundation (K.M.S.). NR 43 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUN PY 2013 VL 34 IS 4 BP 748 EP 754 DI 10.1097/MAO.0b013e31828048ec PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 146AV UT WOS:000319062100030 PM 23512073 ER PT J AU Mougey, EB Chen, C Tantisira, KG Blake, KV Peters, SP Wise, RA Weiss, ST Lima, JJ AF Mougey, E. B. Chen, C. Tantisira, K. G. Blake, K. V. Peters, S. P. Wise, R. A. Weiss, S. T. Lima, J. J. TI Pharmacogenetics of asthma controller treatment SO PHARMACOGENOMICS JOURNAL LA English DT Article DE asthma; Caucasians; controller; genes; pharmacogenetics; polymorphisms ID AIRWAY SMOOTH-MUSCLE; MUSCARINIC RECEPTOR SUBTYPES; IMPROVED LUNG-FUNCTION; GUINEA-PIG TRACHEA; INHALED CORTICOSTEROIDS; PERSISTENT ASTHMA; POLYMORPHISM; MONTELUKAST; ASSOCIATION; SALMETEROL AB The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in beta 2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100 mu g bid), fluticasone propionate (100 mu g) + salmeterol (50 mu g) (FP/Salm) or montelukast (5 or 10 mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (Delta FEV1% pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P = 2.8 x 10(-5)), and rs1461496 in HSPA8 associated with Delta FEV1% pred. For fluticasone, five SNPs in CRHR1 (P = 1.9 x 10(-4)), and three SNPs in COL2A1 associated with ACQ slope and Delta FEV1% pred, respectively. For montelukast, four SNPs in CHRM2 associated with Delta FEV1% pred and predicted an opposite effect compared with fluticasone (P = 9 x 10(-3)). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment. C1 [Mougey, E. B.; Blake, K. V.; Peters, S. P.; Wise, R. A.; Lima, J. J.] ALA Asthma Clin Res Ctr, Jacksonville, FL USA. [Mougey, E. B.; Blake, K. V.; Lima, J. J.] Nemours Childrens Clin, Ctr Pharmacogenet & Translat Res, Jacksonville, FL 32207 USA. [Chen, C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat,Sch Publ Hlth, Boston, MA 02115 USA. [Tantisira, K. G.; Weiss, S. T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Peters, S. P.] Wake Forest Univ, Translat Sci Inst, Hlth Sci Ctr, Ctr Genom & Personalized Med Res, Winston Salem, NC 27109 USA. [Wise, R. A.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Wise, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Lima, JJ (reprint author), Nemours Childrens Clin, Ctr Pharmacogenet & Translat Res, 807 Childrens Way, Jacksonville, FL 32207 USA. EM Jlima@nemours.org OI Wise, Robert/0000-0002-8353-2349 FU Merck; Boehringer-Ingelheim; GSK; Merck Forest; National Institutes of Health [R01HL071394, R01HL074755, K23HL081245, R01HL092197, U01HL065899]; American Lung Association FX Edward Mougey and John Lima received funding from Merck to characterize associations between transporter SNPs, and the pharmacokinetics and pharmacodynamics of montelukast. Stephen Peters received compensation as a consultant to the ALA-ACRC DCC. Robert Wise received compensation as a consultant to the following companies: Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, Sunovion, Centocor, Genentech, Medimmune, Intermune and Pfizerone. Dr Wise is also funded by the following companies: Boehringer-Ingelheim, GSK, Merck Forest.; We acknowledge the ALA-ACRC investigators and research teams who conducted the LOCCS and LODO trials. We would also like to acknowledge Stacey Gray for help with preparation of the manuscript. This work was supported by the National Institutes of Health (R01HL071394, R01HL074755, K23HL081245, R01HL092197, and U01HL065899) and the American Lung Association. NR 57 TC 13 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2013 VL 13 IS 3 BP 242 EP 250 DI 10.1038/tpj.2012.5 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 151GL UT WOS:000319448600006 PM 22370858 ER PT J AU Perlis, RH Fijal, B Dharia, S Houston, JP AF Perlis, R. H. Fijal, B. Dharia, S. Houston, J. P. TI Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder SO PHARMACOGENOMICS JOURNAL LA English DT Article DE anxiety; CRF receptor type 1; duloxetine; single nucleotide polymorphisms ID MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; ANTIDEPRESSANT TREATMENT; DOUBLE-BLIND; ASSOCIATION; ADULTS; GENE AB We examined genetic associations with duloxetine response in generalized anxiety disorder (GAD). Three pooled studies in patients with GAD receiving duloxetine 60-120mg per day (N=164) or placebo (N=95) were used. Associations between 825 single-nucleotide polymorphisms (SNPs) in 61 candidate genes with change in Hamilton Anxiety Scale scores were examined with set-based testing (adjusted for the number of SNPs within each gene); sets with two-sided adjusted P <= 0.05 were examined using repeated measure analysis. Follow-up analysis explored associations of these SNPs with change in Hamilton Rating Scale for Depression-Anxiety Subscale in a 6-week study in duloxetine-treated patients with major depressive disorder (MDD) (N=241). Variants in corticotropin-releasing hormone receptor 1 (CRHR1), dopamine receptor D3 (DRD3), nuclear receptor subfamily group C, member 1 (NR3C1) and phosphodiesterase 1A (PDE1A) were associated with duloxetine response in GAD. Only rs4792888 in CRHR1 showed modest evidence of association with duloxetine response in MDD (P=0.029 in GAD, P=0.054 in MDD). In conclusion, CRHR1 variation merits investigation in pathophysiology of anxiety and its treatment response. C1 [Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Pharmacogen Lab, Boston, MA 02114 USA. [Perlis, R. H.] Harvard Univ, Sch Med, Boston, MA USA. [Fijal, B.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Dharia, S.] PharmaNet i3, Ann Arbor, MI USA. [Houston, J. P.] Lilly USA LLC, Indianapolis, IN 46285 USA. [Houston, J. P.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. RP Houston, JP (reprint author), Lilly USA LLC, Lilly Corp Ctr Mail Code 4103, Indianapolis, IN 46285 USA. EM houston_john_p@lilly.com FU Eli Lilly and Company FX We thank Dr Alexandra Heinloth, Ms Laura Tyler and Ms Barbara McLean for writing and editorial assistance. The parent studies were registered at: http://www.clinicaltrials.gov/ct2/home: NCT00122850, NCT00122863, NCT00122837, and NCT00191061. This work was supported by Eli Lilly and Company and/or any of its subsidiaries. NR 22 TC 11 Z9 11 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2013 VL 13 IS 3 BP 280 EP 285 DI 10.1038/tpj.2011.62 PG 6 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 151GL UT WOS:000319448600011 PM 22249355 ER PT J AU Gordon, CR Susarla, SM Yaremchuk, MJ AF Gordon, Chad R. Susarla, Srinivas M. Yaremchuk, Michael J. TI Reply: Quantitative Assessment of Medial Orbit Fracture Repair Using Computer-Designed Anatomical Plates SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Gordon, Chad R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Susarla, Srinivas M.; Yaremchuk, Michael J.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg, Boston, MA 02116 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg, WACC 435, Boston, MA 02116 USA. EM dr.y@dryaremchuk.com OI Susarla, Srinivas/0000-0003-0155-8260 NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2013 VL 131 IS 6 BP 912E EP 913E DI 10.1097/PRS.0b013e31828bd2ee PG 3 WC Surgery SC Surgery GA 152YG UT WOS:000319567500006 PM 23714814 ER PT J AU Heit, YI Lancerotto, L Del Vecchio, DA Orgill, DP AF Heit, Yvonne I. Lancerotto, Luca Del Vecchio, Dan A. Orgill, Dennis P. TI Reply: The Effects of Negative Pressure on Blood Supply and the Adipogenic Role of Edema SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Heit, Yvonne I.] Univ Magdeburg, Dept Plast Aesthet & Hand Surg, D-39106 Magdeburg, Germany. [Lancerotto, Luca] Univ Padua, Clin Plast Surg, Padua, Italy. [Del Vecchio, Dan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. [Orgill, Dennis P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Plast Surg, Boston, MA 02115 USA. RP Orgill, DP (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dorgill@partners.org OI Orgill, Dennis/0000-0002-8279-7310 NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2013 VL 131 IS 6 BP 932E EP 932E DI 10.1097/PRS.0b013e31828bd2b3 PG 1 WC Surgery SC Surgery GA 152YG UT WOS:000319567500024 PM 23714832 ER PT J AU Reish, RG Damjanovic, B Austen, WG Winograd, J Liao, EC Cetrulo, CL Balkin, DM Colwell, AS AF Reish, Richard G. Damjanovic, Branimir Austen, William G., Jr. Winograd, Jonathan Liao, Eric C. Cetrulo, Curtis L. Balkin, Daniel M. Colwell, Amy S. TI Infection following Implant-Based Reconstruction in 1952 Consecutive Breast Reconstructions: Salvage Rates and Predictors of Success SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ACELLULAR DERMAL MATRIX; COMPLICATIONS; PROSTHESIS; MANAGEMENT; ALLODERM; SURGEONS; ENOUGH; RISK AB Background: Few studies address salvage rates for infection in implant-based breast reconstruction. An understanding of success rates and clinical predictors of failure may help guide management. Method: A retrospective analysis of multisurgeon consecutive implant reconstructions from 2004 to 2010 was performed. Results: Immediate implant-based reconstructions (n = 1952) were performed in 1241 patients. Ninety-nine reconstruction patients (5.1 percent) were admitted for breast erythema and had a higher incidence of smoking (p = 0.007), chemotherapy (p = 0.007), radiation therapy (p = 0.001), and mastectomy skin necrosis (p < 0.0001). There was no difference in age, body mass index, or acellular dermal matrix usage. With intravenous antibiotics, 25 (25.3 percent) reconstruction patients cleared the infection, whereas 74 (74.7 percent) underwent attempted operative salvage (n = 18) or explantation (n = 56). Patients who failed to clear infection had a higher mean white blood cell count at admission (p < 0.0001). Of the attempted operative salvage group, 12 cleared the infection with immediate implant exchange and six eventually lost the implant. Patients who failed implant salvage were more likely to have methicillin-resistant Staphylococcus aureus (p = 0.004). The total explantation rate was 3.2 percent. Following explantation, 32 patients underwent attempted secondary tissue expander insertion. Twenty-six were successful and six had recurrent infection and implant loss. There were no differences in time interval to tissue expander insertion between successful and unsuccessful secondary operations. Conclusions: Salvage with intravenous antibiotics and implant exchange was successful in 37.3 percent of patients. Smoking, irradiation, chemotherapy, and mastectomy skin necrosis were predictors for developing infection. Patients with a higher white blood cell count at admission and methicillin-resistant S. aureus were more likely to fail implant salvage. There was no association with time interval to tissue expander insertion and secondary explantation. C1 [Reish, Richard G.; Damjanovic, Branimir; Austen, William G., Jr.; Winograd, Jonathan; Liao, Eric C.; Cetrulo, Curtis L.; Balkin, Daniel M.; Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Colwell, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, 15 Parkman St, Boston, MA 02114 USA. EM acolwell@partners.org NR 20 TC 33 Z9 34 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2013 VL 131 IS 6 BP 1223 EP 1230 DI 10.1097/PRS.0b013e31828bd377 PG 8 WC Surgery SC Surgery GA 152YG UT WOS:000319567500036 PM 23714788 ER PT J AU Schacht, JP Anton, RF Randall, PK Li, XB Henderson, S Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Randall, Patrick K. Li, Xingbao Henderson, Scott Myrick, Hugh TI Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics SO PSYCHOPHARMACOLOGY LA English DT Article DE Alcoholism; Anticonvulsant; Craving; Neuroimaging; Relapse ID ANTERIOR CINGULATE CORTEX; COMPULSIVE DRINKING SCALE; PREFRONTAL CORTEX; DEPENDENT INDIVIDUALS; ABSTINENT ALCOHOLICS; ETHANOL WITHDRAWAL; RECEPTOR FUNCTION; GENE-EXPRESSION; DOUBLE-BLIND; GABAPENTIN AB Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking. C1 [Schacht, Joseph P.; Anton, Raymond F.; Randall, Patrick K.; Li, Xingbao; Henderson, Scott; Myrick, Hugh] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute on Alcohol Abuse and Alcoholism [T32 AA007474, K05 AA017435]; Hythiam, Inc. FX This work was conducted under an unrestricted grant from Hythiam, Inc. This funding source had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the paper, or in the decision to submit for publication. Drs. Schacht and Anton are supported by grants from the National Institute on Alcohol Abuse and Alcoholism (T32 AA007474 and K05 AA017435). Portions of this work were presented as a poster at the 34th Annual Meeting of the Research Society on Alcoholism (June 2011, Atlanta, GA, USA). NR 57 TC 10 Z9 11 U1 10 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 2013 VL 227 IS 4 BP 627 EP 637 DI 10.1007/s00213-013-2996-x PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 150XF UT WOS:000319424200006 PM 23389755 ER PT J AU Doyle, PJ Hula, WD Hula, SNA Stone, CA Wambaugh, JL Ross, KB Schumacher, JG AF Doyle, Patrick J. Hula, William D. Hula, Shannon N. Austermann Stone, Clement A. Wambaugh, Julie L. Ross, Katherine B. Schumacher, James G. TI Self- and surrogate-reported communication functioning in aphasia SO QUALITY OF LIFE RESEARCH LA English DT Article DE Outcomes assessment; Self-assessment; Factor analysis; Aphasia ID QUALITY-OF-LIFE; STROKE IMPACT SCALE; MEASUREMENT INVARIANCE; FACTORIAL INVARIANCE; PSYCHOMETRIC EVALUATION; OUTCOME MEASURE; RASCH ANALYSIS; CES-D; PROXY; RELIABILITY AB To evaluate the dimensionality and measurement invariance of the aphasia communication outcome measure (ACOM), a self- and surrogate-reported measure of communicative functioning in aphasia. Responses to a large pool of items describing communication activities were collected from 133 community-dwelling persons with aphasia of a parts per thousand yen 1 month post-onset and their associated surrogate respondents. These responses were evaluated using confirmatory and exploratory factor analysis. Chi-square difference tests of nested factor models were used to evaluate patient-surrogate measurement invariance and the equality of factor score means and variances. Association and agreement between self- and surrogate reports were examined using correlation and scatterplots of pairwise patient-surrogate differences. Three single-factor scales (Talking, Comprehension, and Writing) approximating patient-surrogate measurement invariance were identified. The variance of patient-reported scores on the Talking and Writing scales was higher than surrogate-reported variances on these scales. Correlations between self- and surrogate reports were moderate-to-strong, but there were significant disagreements in a substantial number of individual cases. Despite minimal bias and relatively strong association, surrogate reports of communicative functioning in aphasia are not reliable substitutes for self-reports by persons with aphasia. Furthermore, although measurement invariance is necessary for direct comparison of self- and surrogate reports, the costs of obtaining invariance in terms of scale reliability and content validity may be substantial. Development of non-invariant self- and surrogate report scales may be preferable for some applications. C1 [Doyle, Patrick J.; Hula, William D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. [Doyle, Patrick J.; Hula, William D.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Hula, Shannon N. Austermann] VA Pittsburgh Healthcare Syst, Res Serv, Pittsburgh, PA USA. [Stone, Clement A.] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA. [Wambaugh, Julie L.] VA Salt Lake City Healthcare Syst, Res Serv, Salt Lake City, UT USA. [Wambaugh, Julie L.] Univ Utah, Dept Commun Sci & Disorders, Salt Lake City, UT USA. [Ross, Katherine B.] Phoenix VA Healthcare Syst, Audiol & Speech Pathol, Phoenix, AZ USA. [Schumacher, James G.] VA Pittsburgh Healthcare Syst, Audiol & Speech Pathol, Pittsburgh, PA USA. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. EM william.hula@va.gov FU VA Rehabilitation Research & Development Merit Review Award [C6098R]; Career Development Award [6210 M]; VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center FX This work was supported by VA Rehabilitation Research & Development Merit Review Award C6098R, Career Development Award 6210 M, and the VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center. An earlier version of this work was presented at the Clinical Aphasiology Conference, May 27, 2010, Isle of Palms, SC, USA. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 58 TC 3 Z9 3 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD JUN PY 2013 VL 22 IS 5 BP 957 EP 967 DI 10.1007/s11136-012-0224-5 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 152FQ UT WOS:000319516800004 PM 22729711 ER PT J AU Cella, D Butt, Z Kindler, HL Fuchs, CS Bray, S Barlev, A Oglesby, A AF Cella, David Butt, Zeeshan Kindler, Hedy Lee Fuchs, Charles S. Bray, Sarah Barlev, Arie Oglesby, Alan TI Validity of the FACT Hepatobiliary (FACT-Hep) questionnaire for assessing disease-related symptoms and health-related quality of life in patients with metastatic pancreatic cancer SO QUALITY OF LIFE RESEARCH LA English DT Article DE Health-related quality of life; Questionnaire; Pancreatic cancer; Patient-reported outcomes ID FUNCTIONAL ASSESSMENT; INSTRUMENTS; THERAPY; VALIDATION; INDEX AB Evaluate reliability and validity of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire and its derivative FACT Hepatobiliary Symptom Indexes (FHSI-18 and FHSI-8) in people with metastatic pancreatic cancer. Self-reported questionnaire data from a randomized controlled Phase II study evaluating the efficacy and safety of conatumumab (AMG 655), ganitumab (AMG 479) or placebo combined with gemcitabine were evaluated. The following were assessed: internal consistency, using Cronbach's alpha; discriminant validity, comparing baseline patient-reported outcomes (PRO) scores across Eastern Cooperative Oncology Group (ECOG) performance status (PS) levels; and ability to detect change, comparing change from baseline PRO score at each cycle across PS and tumour response groups. The analysis included 96 patients. All scale scores demonstrated good internal consistency (Cronbach's alpha > 0.7) and discriminant validity. Baseline scores were significantly poorer among patients with PS = 1 versus patients with PS = 0 (e.g. difference in FACT-Hep total score -17.27; p < 0.001). Ability to detect change was established for Cycles 2/3 versus baseline; PRO scores reduced in the PS-worsened group versus the PS-stable group (e.g. difference in FACT-Hep total score -24.29; p < 0.001). All PRO scale scores showed significant decline for progressive disease versus stable disease (e.g. difference in FACT-Hep total score -12.58; p = 0.004). Changes on the FHSI-18 and FHSI-8 scales were similar in magnitude whether ECOG improved or worsened. FACT-Hep detects change and is a reliable and valid instrument for measuring health-related quality of life in patients with metastatic pancreatic cancer. C1 [Cella, David; Butt, Zeeshan] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Kindler, Hedy Lee] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bray, Sarah] Amgen Inc, Cambridge, England. [Barlev, Arie; Oglesby, Alan] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Cella, D (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 720 N Lake Shore Dr,7th Floor, Chicago, IL 60611 USA. EM d-cella@northwestern.edu FU Amgen Inc.; National Center for Research Resources, National Institutes of Health [KL2RR025740] FX Medical writing assistance was provided by ApotheCom ScopeMedical Ltd, funded by Amgen Inc. All authors had full access to the data and had final responsibility for the decision to submit the manuscript. This study was funded by Amgen Inc. Zeeshan Butt's work on this manuscript was supported in part by grant KL2RR025740 from the National Center for Research Resources, National Institutes of Health. NR 22 TC 6 Z9 6 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD JUN PY 2013 VL 22 IS 5 BP 1105 EP 1112 DI 10.1007/s11136-012-0217-4 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 152FQ UT WOS:000319516800019 PM 22678353 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Digital Breast Tomosynthesis: A Better Mammogram SO RADIOLOGY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 5 Parkman St,Suite 219, Boston, MA 02114 USA. EM dkopans@partners.org NR 3 TC 5 Z9 5 U1 0 U2 13 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2013 VL 267 IS 3 BP 968 EP 969 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151FF UT WOS:000319445400041 PM 23704296 ER PT J AU Wicky, S Pinto, EG Oklu, R AF Wicky, Stephan Pinto, Erique Guedes Oklu, Rahmi TI Catheter-Directed Thrombolysis of Arterial Thrombosis SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE thrombosis; catheter-directed thrombolysis; artery ID ACUTE LIMB ISCHEMIA; PERIPHERAL ARTERIAL; RANDOMIZED TRIAL; LOWER-EXTREMITY; ANGIOJET; SYSTEM; THROMBECTOMY; SURGERY; THROMBOEMBOLECTOMY; STREPTOKINASE AB Thrombotic or embolic arterial occlusive disease can lead to profound ischemia and, without emergent revascularization, is associated with significant morbidity and mortality. Significant advances in the management of arterial occlusive disease range from newer thrombolytic agents to innovative catheter designs to enhance thrombolysis and thrombectomy. Most of these advances have been directed toward the management of acute limb ischemia; therefore, we review the management of limb ischemia with emphasis on endovascular interventions. C1 [Wicky, Stephan; Pinto, Erique Guedes; Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@partners.org NR 32 TC 6 Z9 7 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD JUN PY 2013 VL 39 IS 4 BP 441 EP 445 DI 10.1055/s-0033-1334482 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 152AM UT WOS:000319501600014 PM 23483456 ER PT J AU Oklu, R Wicky, S AF Oklu, Rahmi Wicky, Stephan TI Catheter-Directed Thrombolysis of Deep Venous Thrombosis SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE thrombosis; catheter-directed thrombolysis; vein; DVT ID PERCUTANEOUS MECHANICAL THROMBECTOMY; TISSUE-PLASMINOGEN-ACTIVATOR; VASC INTERV RADIOL; QUALITY IMPROVEMENT GUIDELINES; RANDOMIZED CONTROLLED-TRIAL; VEIN-THROMBOSIS; PHARMACOMECHANICAL THROMBECTOMY; POSTTHROMBOTIC SYNDROME; PULMONARY-EMBOLISM; OF-LIFE AB Venous thrombosis is a major public health problem associated with significant morbidity and mortality and has a substantial impact on the quality of life. Over the years, it has becomemore apparent that anticoagulation alone in the treatment of deep venous thrombosis (DVT) is insufficient in the prevention of postthrombotic syndrome, which adversely impacts the quality of life of the patient, and it is insufficient in preventing recurrence of DVT. With the advent of innovative catheter designs to deliver thrombolytic therapies in the treatment of DVT, there have been significant advances in the management of DVT. We review the management of DVT with emphasis on catheter-directed interventions. C1 [Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@partners.org NR 48 TC 8 Z9 11 U1 0 U2 9 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD JUN PY 2013 VL 39 IS 4 BP 446 EP 451 DI 10.1055/s-0033-1334142 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 152AM UT WOS:000319501600015 PM 23483455 ER PT J AU Sun, N Liu, Y Qin, L Lee, H Weissleder, R Ham, D AF Sun, Nan Liu, Yong Qin, Ling Lee, Hakho Weissleder, Ralph Ham, Donhee TI Small NMR biomolecular sensors SO SOLID-STATE ELECTRONICS LA English DT Article; Proceedings Paper CT 42nd European Solid-State Device Research Conference (ESSDERC) CY SEP, 2012 CL Bordeaux, FRANCE DE Nuclear magnetic resonance (NMR); Radio-frequency (RF) integrated circuits; CMOS integrated circuits; Biomolecular sensing; Biosensor Magnetic particles ID NUCLEAR-MAGNETIC-RESONANCE; CMOS TECHNOLOGY; CELLS; MANIPULATION; OSCILLATORS; BIOSENSOR; HYBRID; SYSTEM; NOISE AB By combining the physics of nuclear magnetic resonance (NMR) and silicon radio-frequency (RF) integrated circuits, we recently created progressively smaller NMR systems, which we originally reported in Refs. [1-4 Our strategy for NMR system miniaturization proved effective, culminating in the smallest prototype 13,4] that weighs 0.1 kg and can be held at the palm of the hand. These small, low-cost NMR systems can be useful as biomolecular sensors in the personalized medicine setting, and we demonstrated their ability to detect proteins, compounds, and human cancer cells. The present paper, which is not a new technical contribution, reviews these developments. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Sun, Nan] Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA. [Liu, Yong] IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA. [Qin, Ling; Ham, Donhee] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Sun, N (reprint author), Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA. EM nansun@mail.utexas.edu; donhee@seas.harvard.edu RI Liu, Yong/J-3636-2014 NR 37 TC 9 Z9 9 U1 5 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0038-1101 J9 SOLID STATE ELECTRON JI Solid-State Electron. PD JUN PY 2013 VL 84 BP 13 EP 21 DI 10.1016/j.sse.2013.02.005 PG 9 WC Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Engineering; Physics GA 152QV UT WOS:000319547100003 ER PT J AU Devan, WJ Falcone, GJ Anderson, CD Jagiella, JM Schmidt, H Hansen, BM Jimenez-Conde, J Giralt-Steinhauer, E Cuadrado-Godia, E Soriano, C Ayres, AM Schwab, K Kassis, SB Valant, V Pera, J Urbanik, A Viswanathan, A Rost, NS Goldstein, JN Freudenberger, P Stogerer, EM Norrving, B Tirschwell, DL Selim, M Brown, DL Silliman, SL Worrall, BB Meschia, JF Kidwell, CS Montaner, J Fernandez-Cadenas, I Delgado, P Greenberg, SM Roquer, J Lindgren, A Slowik, A Schmidt, R Woo, D Rosand, J Biffi, A AF Devan, William J. Falcone, Guido J. Anderson, Christopher D. Jagiella, Jeremiasz M. Schmidt, Helena Hansen, Bjorn M. Jimenez-Conde, Jordi Giralt-Steinhauer, Eva Cuadrado-Godia, Elisa Soriano, Carolina Ayres, Alison M. Schwab, Kristin Kassis, Sylvia Baedorf Valant, Valerie Pera, Joanna Urbanik, Andrzej Viswanathan, Anand Rost, Natalia S. Goldstein, Joshua N. Freudenberger, Paul Stoegerer, Eva-Maria Norrving, Bo Tirschwell, David L. Selim, Magdy Brown, Devin L. Silliman, Scott L. Worrall, Bradford B. Meschia, James F. Kidwell, Chelsea S. Montaner, Joan Fernandez-Cadenas, Israel Delgado, Pilar Greenberg, Steven M. Roquer, Jaume Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Woo, Daniel Rosand, Jonathan Biffi, Alessandro CA Int Stroke Genetics Consortium TI Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage SO STROKE LA English DT Article DE common genetic variants; genetics; genes; heritability; intracerebral hemorrhage; stroke ID APOLIPOPROTEIN-E GENOTYPE; COMMON SNPS EXPLAIN; AMYLOID ANGIOPATHY; HEMATOMA EXPANSION; ALZHEIMER-DISEASE; LARGE PROPORTION; INCREASES RISK; HUMAN HEIGHT; ASSOCIATION; WARFARIN AB Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results-ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOE loci and at 12% (SE, 4%) for APOE. Conclusions-Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified. C1 [Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Ayres, Alison M.; Schwab, Kristin; Kassis, Sylvia Baedorf; Valant, Valerie; Viswanathan, Anand; Rost, Natalia S.; Greenberg, Steven M.; Roquer, Jaume; Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Roquer, Jaume; Biffi, Alessandro] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Kassis, Sylvia Baedorf; Valant, Valerie; Rost, Natalia S.; Roquer, Jaume; Biffi, Alessandro] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Kassis, Sylvia Baedorf; Valant, Valerie; Rost, Natalia S.; Roquer, Jaume; Biffi, Alessandro] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Jagiella, Jeremiasz M.; Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Schmidt, Helena; Freudenberger, Paul] Med Univ Graz, Inst Mol Biol & Med Biochem, Graz, Austria. [Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Univ Autonoma Barcelona, Neurovasc Res Unit, Dept Neurol, E-08193 Barcelona, Spain. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Cuadrado-Godia, Elisa; Soriano, Carolina; Rosand, Jonathan] Univ Autonoma Barcelona, Program Inflammat & Cardiovasc Disorders, Inst Hosp Mar Invest Med, E-08193 Barcelona, Spain. [Urbanik, Andrzej; Schmidt, Reinhold] Med Univ Graz, Dept Radiol, Graz, Austria. [Stoegerer, Eva-Maria] Med Univ Graz, Dept Neurol, Graz, Austria. [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Kidwell, Chelsea S.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Neurovasc Res Lab, Hosp Vall dHebron, Inst Recerca, E-08193 Barcelona, Spain. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Neurovasc Unit, Hosp Vall dHebron, Inst Recerca, E-08193 Barcelona, Spain. [Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI JIMENEZ-CONDE, JORDI/C-1941-2012; Montaner, Joan/D-3063-2015; Goldstein, Joshua/H-8953-2016; IBIS, NEUROVASCULAR/O-1855-2015; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Hansen, Bjorn/0000-0001-8661-9063; Brown, Devin/0000-0002-9815-3421; Norrving, Bo/0000-0002-8024-5096; Ayres, Alison/0000-0002-5492-1695; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke grant [R01NS059727]; Keane Stroke Genetics Research Fund; Edward and Maybeth Sonn Research Fund; University of Michigan General Clinical Research Center grant [M01 RR000042]; National Center for Research Resources; Spain's Ministry of Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Red HERACLES) [RD06/0009]; Polish Ministry of Education grant [N N402 083934]; Swedish Research Council [K2010-61X-20378-04-3]; Swedish Stroke Association; Lund University; King Gustav V and Queen Victoria's foundations; EUSTROKE 7FP Health [F2-08-202213]; Spanish Government [PI10/01212]; Austrian Science Fund (FWF) [P20545-P05, P13180]; Medical University of Graz; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775011 N]; American Brain Foundation Clinical Research Training Fellowship; National Institutes of Health-National Institute of Neurological Disorders and Stroke [R01NS059727, 1K23NS064052, 5K23NS059774, 5R01AG026484-08, U01NS069208, U01NS069763, R01NS063925]; National Institutes of Health [5R01NS070834-03]; Miguel Servet program from the Spanish Ministry of Health [CP09/136]; CSL Behring; Hoffman La-Roche FX All funding entities had no involvement in design, collection, analysis, and interpretation, writing of the report, and in the decision to submit the article for publication. Genetics of Cerebral Hemorrhage on Anticoagulation: This study was funded by the National Institutes of Health-National Institute of Neurological Disorders and Stroke grant R01NS059727, the Keane Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research Fund, by the University of Michigan General Clinical Research Center grant M01 RR000042, and by a grant from the National Center for Research Resources. Hospital del Mar Intracerebral Hemorrhage (ICH) Study: This study was funded by Spain's Ministry of Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Red HERACLES RD06/0009. FEDER). The Jagiellonian University Hemorrhagic Stroke Study: This study is supported by the Polish Ministry of Education grant N N402 083934. The Lund Stroke Register ICH Study: This study was funded by the Swedish Research Council (K2010-61X-20378-04-3), the Swedish Stroke Association, the Lund University, and the King Gustav V and Queen Victoria's foundations. The Hospital Vall d'Hebron ICH Study: This study received the European Stroke Network grants EUSTROKE 7FP Health F2-08-202213 and the Spanish Government grant PI10/01212. The Medical University of Graz ICH Study: Control subjects of this study are from the Austrian Stroke Prevention Study, a population-based study funded by the Austrian Science Fund (FWF) grants P20545-P05 and P13180. The Medical University of Graz supports the databank of the Austrian Stroke Prevention Study. The authors are supported by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775011 N; Drs Biffi and Anderson), an American Brain Foundation Clinical Research Training Fellowship (Dr Anderson), the National Institutes of Health-National Institute of Neurological Disorders and Stroke (Dr Rost [1K23NS064052], Dr Goldstein [5K23NS059774], Dr Greenberg [5R01AG026484-08], and Dr Roquer [R01NS059727, U01NS069208, U01NS069763, R01NS063925]), the National Institutes of Health (5R01NS070834-03; Dr Greenberg), and the Miguel Servet program from the Spanish Ministry of Health (CP09/136; Dr Delgado).; Dr Goldstein has received consultancy fees, travel and accommodation expenses reimbursement, and grant support from CSL Behring. Dr Greenberg has received consultancy fees and support from Hoffman La-Roche. The other authors have no conflicts to report. NR 29 TC 23 Z9 24 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2013 VL 44 IS 6 BP 1578 EP U191 DI 10.1161/STROKEAHA.111.000089 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 151MU UT WOS:000319465400022 PM 23559261 ER PT J AU Brouwers, HB Backes, D Kimberly, WT Schwab, K Romero, JM Velthuis, BK Klijn, CJM Ogilvy, CS Regli, L Greenberg, SM Rosand, J Rinkel, GJE Goldstein, JN AF Brouwers, H. Bart Backes, Daan Kimberly, W. Taylor Schwab, Kristin Romero, Javier M. Velthuis, Birgitta K. Klijn, Catharina J. M. Ogilvy, Christopher S. Regli, Luca Greenberg, Steven M. Rosand, Jonathan Rinkel, Gabriel J. E. Goldstein, Joshua N. TI Computed Tomography Angiography Spot Sign Does Not Predict Case Fatality in Aneurysmal Subarachnoid Hemorrhage With Intraparenchymal Extension SO STROKE LA English DT Article DE CTA spot sign; in-hospital death; intracerebral hemorrhage; subarachnoid hemorrhage ID ACUTE INTRACEREBRAL HEMORRHAGE; IN-HOSPITAL MORTALITY; HEMATOMA EXPANSION; IDENTIFIES PATIENTS; HIGHEST RISK; OUTCOMES; SCORE AB Background and Purpose-Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Methods-We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. Results-In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. Conclusions-The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. C1 [Brouwers, H. Bart; Kimberly, W. Taylor; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Brouwers, H. Bart; Kimberly, W. Taylor; Schwab, Kristin; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Brouwers, H. Bart; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Brouwers, H. Bart; Backes, Daan; Klijn, Catharina J. M.; Regli, Luca; Rinkel, Gabriel J. E.] Rudolf Magnus Inst Neurosci, Dept Neurol & Neurosurg, NL-3508 TA Utrecht, Netherlands. [Velthuis, Birgitta K.] Univ Utrecht, Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [Regli, Luca] Univ Zurich, Univ Zurich Hosp, Dept Neurosurg, Zurich, Switzerland. RP Brouwers, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM brouwers@chgr.mgh.harvard.edu RI Klijn, C.J.M. (Karin)/E-1700-2016; Goldstein, Joshua/H-8953-2016 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [R01NS073344, R01NS059727, 5K23NS059774]; American Heart Association Grant [0755984T]; Andrew D. Heitman Neurovascular Research Fund; NIH-NINDS SPOTRIAS fellowship [P50NS051343]; NIH; AHA; NINDS FX The project described was supported by grant numbers R01NS073344, R01NS059727, and 5K23NS059774 from the National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS), American Heart Association Grant Number 0755984T, and the Andrew D. Heitman Neurovascular Research Fund. Dr Brouwers was supported by the NIH-NINDS SPOTRIAS fellowship grant P50NS051343. Dr Kimberly received a research grant from Andrew D. Heitman Neurovascular Research Fund. Dr Greenberg received a research grant from NIH. Dr Rosand received a research grant from NIH and AHA; Dr Goldstein received a research grant from NINDS. NR 16 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2013 VL 44 IS 6 BP 1590 EP 1594 DI 10.1161/STROKEAHA.111.000586 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 151MU UT WOS:000319465400024 PM 23572475 ER PT J AU Adib-Samii, P Rost, N Traylor, M Devan, W Biffi, A Lanfranconi, S Fitzpatrick, K Bevan, S Kanakis, A Valant, V Gschwendtner, A Malik, R Richie, A Gamble, D Segal, H Parati, EA Ciusani, E Holliday, EG Maguire, J Wardlaw, J Worrall, B Bis, J Wiggins, KL Longstreth, W Kittner, SJ Cheng, YC Mosley, T Falcone, GJ Furie, KL Leiva-Salinas, C Lau, BC Khan, MS Sharma, P Fornage, M Mitchell, BD Psaty, BM Sudlow, C Levi, C Boncoraglio, GB Rothwell, PM Meschia, J Dichgans, M Rosand, J Markus, HS AF Adib-Samii, Poneh Rost, Natalia Traylor, Matthew Devan, William Biffi, Alessandro Lanfranconi, Silvia Fitzpatrick, Kaitlin Bevan, Steve Kanakis, Allison Valant, Valerie Gschwendtner, Andreas Malik, Rainer Richie, Alexa Gamble, Dale Segal, Helen Parati, Eugenio A. Ciusani, Emilio Holliday, Elizabeth G. Maguire, Jane Wardlaw, Joanna Worrall, Bradford Bis, Joshua Wiggins, Kerri L. Longstreth, Will Kittner, Steve J. Cheng, Yu-Ching Mosley, Thomas Falcone, Guido J. Furie, Karen L. Leiva-Salinas, Carlos Lau, Benison C. Khan, Muhammed Saleem Sharma, Pankaj Fornage, Myriam Mitchell, Braxton D. Psaty, Bruce M. Sudlow, Cathie Levi, Christopher Boncoraglio, Giorgio B. Rothwell, Peter M. Meschia, James Dichgans, Martin Rosand, Jonathan Markus, Hugh S. CA Australian Stroke Genetics Collabo Wellcome Trust Case-Control Consor METASTROKE Int Stroke Genetics Consortium TI 17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status SO STROKE LA English DT Article DE genetics; Genome-wide Association Study; leukoaraiosis; small-vessel disease; stroke ID GENOME-WIDE ASSOCIATION; ATRIAL-FIBRILLATION; RISK; METAANALYSIS; CLASSIFICATION; POPULATION; EXPRESSION; SUBTYPES; COHORT; MRI AB Background and Purpose-Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods-We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results-Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions-This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction. C1 [Adib-Samii, Poneh; Traylor, Matthew; Lanfranconi, Silvia; Bevan, Steve; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Rost, Natalia; Devan, William; Biffi, Alessandro; Fitzpatrick, Kaitlin; Kanakis, Allison; Valant, Valerie; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rost, Natalia; Devan, William; Biffi, Alessandro; Fitzpatrick, Kaitlin; Kanakis, Allison; Valant, Valerie; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rost, Natalia] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Gschwendtner, Andreas; Malik, Rainer; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany. [Richie, Alexa; Gamble, Dale; Maguire, Jane] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Segal, Helen; Rothwell, Peter M.] Univ Oxford, Nuffield Dept Neurosci, Stroke Prevent Res Unit, Oxford OX1 2JD, England. [Parati, Eugenio A.; Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Ciusani, Emilio] Fdn IRCCS Ist Neurol Carlo Besta, Lab Clin Pathol & Med Genet, Milan, Italy. [Holliday, Elizabeth G.; Levi, Christopher] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Hunter Med Res Inst, Callaghan, NSW 2308, Australia. [Holliday, Elizabeth G.; Levi, Christopher] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Meschia, James] Univ Newcastle, Prior Res Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Meschia, James] Univ Newcastle, Fac Hlth, Sch Nursing & Midwifery, Callaghan, NSW 2308, Australia. [Wardlaw, Joanna; Levi, Christopher] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Wardlaw, Joanna; Levi, Christopher] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Worrall, Bradford] Univ Virginia, Charlottesville, VA USA. [Bis, Joshua; Wiggins, Kerri L.; Longstreth, Will] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Kittner, Steve J.; Cheng, Yu-Ching] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Kittner, Steve J.] Vet Affairs Med Ctr, Baltimore, MD USA. [Mosley, Thomas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Furie, Karen L.] Brown Univ, Dept Neurol, Providence, RI 02912 USA. [Leiva-Salinas, Carlos; Lau, Benison C.] Univ Virginia, Dept Radiol, Charlottesville, VA USA. [Khan, Muhammed Saleem; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Markus, HS (reprint author), Univ London, London SW17 0RE, England. EM hmarkus@sgul.ac.uk RI Boncoraglio, Giorgio/B-8647-2011; Blackwell, Jenefer/H-3015-2015; Falcone, Guido/L-2287-2016; OI Mitchell, Braxton/0000-0003-4920-4744; Falcone, Guido/0000-0002-6407-0302; Wardlaw, Joanna/0000-0002-9812-6642; Traylor, Matthew/0000-0001-6624-8621; Gillman, Matthew/0000-0002-2340-6930; Plomin, Robert/0000-0002-0756-3629; Bevan, Steve/0000-0003-0490-6830 FU Stroke Association; MRC (Training Fellowship); NINDS [K23NS064052]; Wellcome Trust (WTCCC2); Intramural Research Program (NIA); Intramural Research Program (MGH); Intramural Research Program (ISGS); National Institute for Neurological Disorders and Stroke (SWISS); National Institute for Neurological Disorders and Stroke (GASROS); National Institute for Neurological Disorders and Stroke (ISGS); National Institute for Neurological Disorders and Stroke (CHS); National Institute for Neurological Disorders and Stroke (HVH); National Institute for Neurological Disorders and Stroke (GEOS); Bugher Foundation of the American Heart Association; MGH Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (GASROS); National Institutes of Health Genes, Environment and Health Initiative, Medical Research Service of the Department of Veterans Affairs and Centers for Disease Control (GEOS); National Health & Medical Research Council (ASGC); Italian Ministry of Health (Milan); National Human Genome Research Institute (GASROS); National Human Genome Research Institute (ARIC); National Heart, Lung, and Blood Institute (ARIC); National Heart, Lung, and Blood Institute (CHS); National Heart, Lung, and Blood Institute (HVH); Henry Smith Charity; British Council (BRAINS) FX The principal funding for this study was provided by the Stroke Association. The authors are supported by MRC (Training Fellowship, Dr Adib-Samii) and NINDS (K23NS064052, Dr Rost). Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust (WTCCC2), the Intramural Research Program (NIA; MGH, ISGS), National Institute for Neurological Disorders and Stroke (SWISS, GASROS, ISGS, CHS, HVH, GEOS), Bugher Foundation of the American Heart Association, MGH Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (GASROS), National Institutes of Health Genes, Environment and Health Initiative, Medical Research Service of the Department of Veterans Affairs and Centers for Disease Control (GEOS), National Health & Medical Research Council (ASGC), Italian Ministry of Health (Milan), National Human Genome Research Institute (GASROS), ARIC), National Heart, Lung, and Blood Institute (ARIC, CHS, HVH), Henry Smith Charity, and the British Council (BRAINS). NR 35 TC 21 Z9 21 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2013 VL 44 IS 6 BP 1609 EP + DI 10.1161/STROKEAHA.113.679936 PG 31 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 151MU UT WOS:000319465400028 PM 23674528 ER PT J AU Dirnagl, U Hakim, A Macleod, M Fisher, M Howells, D Alan, SM Steinberg, G Planas, A Boltze, J Savitz, S Iadecola, C Meairs, S AF Dirnagl, Ulrich Hakim, Antoine Macleod, Malcolm Fisher, Marc Howells, David Alan, Stuart M. Steinberg, Gary Planas, Anna Boltze, Johannes Savitz, Sean Iadecola, Costantino Meairs, Stephen TI A Concerted Appeal for International Cooperation in Preclinical Stroke Research SO STROKE LA English DT Article DE cerebral ischemia; roadblock; translational medicine ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE ISCHEMIC-STROKE; NEUROLOGICAL DISEASE; NEUROVASCULAR UNIT; CLINICAL STROKE; EMBOLIC STROKE; CARDIAC-ARREST; THROMBOLYSIS; MECHANISMS; BEDSIDE C1 [Dirnagl, Ulrich] Charite, Ctr Stroke Res, Dept Neurol & Expt Neurol, D-10098 Berlin, Germany. [Hakim, Antoine] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Macleod, Malcolm] Univ Edinburgh, Ctr Clin Brain Sci, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA. [Howells, David] Melbourne Brain Ctr, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia. [Alan, Stuart M.] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Steinberg, Gary] Stanford Univ, Sch Med, Dept Neurosurg, Stanford Stroke Ctr, Stanford, CA 94305 USA. [Steinberg, Gary] Stanford Univ, Sch Med, Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA. [Planas, Anna] Univ Barcelona, Invest Biomed August Pi & Sunyer IDIBAPS, E-08007 Barcelona, Spain. [Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, Leipzig, Germany. [Boltze, Johannes] Translat Ctr Regenerat Med, Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boltze, Johannes] Harvard Univ, Sch Med, Boston, MA USA. [Savitz, Sean] Univ Texas Med Sch Houston, Stroke Team, Dept Neurol, Houston, TX USA. [Iadecola, Costantino] Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY USA. [Meairs, Stephen] Heidelberg Univ, Dept Neurol, Univ Med Mannheim, Heidelberg, Germany. RP Dirnagl, U (reprint author), Charite, Ctr Stroke Res Berlin, Dept Neurol & Expt Neurol, Campus Mitte, D-10098 Berlin, Germany. EM Ulrich.dirnagl@charite.de RI Planas, Anna /J-5991-2014; OI Planas, Anna /0000-0002-6147-1880; Howells, David/0000-0002-2512-7724; Dirnagl, Ulrich/0000-0003-0755-6119; Macleod, Malcolm Robert/0000-0001-9187-9839 FU Medical Research Council [G0800803]; NINDS NIH HHS [R01 NS034179, R01 NS073666]; National Centre for the Replacement, Refinement and Reduction of Animals in Research [NC/L000970/1] NR 66 TC 39 Z9 39 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2013 VL 44 IS 6 BP 1754 EP 1760 DI 10.1161/STROKEAHA.113.000734 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 151MU UT WOS:000319465400054 PM 23598526 ER PT J AU Horgan, S Meireles, OR Jacobsen, GR Sandler, BJ Ferreres, A Ramamoorthy, S Savides, T Katagiri, T Dotai, T Sedrak, M Majid, SF Nijhawan, S Talamini, MA AF Horgan, Santiago Meireles, Ozanan R. Jacobsen, Garth R. Sandler, Bryan J. Ferreres, Alberto Ramamoorthy, Sonia Savides, Thomas Katagiri, Toshio Dotai, Takayuki Sedrak, Michael Majid, Saniea F. Nijhawan, Sheetal Talamini, Mark A. TI Broad clinical utilization of NOTES: is it safe? SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons (SAGES) CY MAR 30-APR 02, 2011 CL San Antonio, TX SP Soc Amer Gastrointestinal & Endoscop Surg (SAGES) DE Achalasia; Cholecystectomy; Clinical papers/trials/research; Endoscopy; NOTES; Obesity ID ENDOSCOPIC CHOLECYSTECTOMY; PORCINE MODEL; SURGERY; SURVIVAL AB Natural orifice transluminal endoscopic surgery (NOTES) has been the focus of several studies as a less invasive alternative to conventional laparoscopy to access and treat intracavitary organs. For the last 5 years, much has been accomplished with animal studies, yet the clinical utilization of this novel technique is still modest. After 2 years of experience in the laboratory, we started our clinical experience. We report our experience with clinical utilization of NOTES procedures from 2007 to 2010. Under UCSD institutional review board-approved trials, 104 patients were enrolled under seven different NOTES protocols from 2007 to 2010, where a NOTES procedure was offered as an alternative to conventional treatments. The treated pathologies were cholelithiasis, biliary dyskinesia, acute and chronic appendicitis, ventral hernias, morbid obesity, and achalasia. The access routes included transgastric (TG), transvaginal (TV), transesophageal (TE), and perirectal (PR). Among the 104 patients enrolled, 103 underwent a surgical procedure starting with diagnostic laparoscopy, and 94 cases were deemed appropriate to proceed via a NOTES approach. There were 9 aborted NOTES procedures at the time of the initial peritoneoscopy before creating a NOTES access route. The reasons to not proceed with a NOTES procedure in the TV cholecystectomy group (n = 5) were a large amount of pelvic adhesions in 4 patients and a severe inflammation of the gallbladder in 1 patient. In the TG cholecystectomy group (n = 1), it was severe inflammation of the gallbladder. In the TG appendectomy group (n = 1), it was the presence of localized peritonitis. In the TE endoscopic myotomy group (n = 2), it was the presence of megaesophagus with an inability to clean the esophagus of food debris. The NOTES procedures performed were 48 TV cholecystectomies, 4 TV appendectomies, 8 TG cholecystectomies, 2 PR peritoneoscopies, 3 TG appendectomies, 3 TV ventral hernia repairs, 5 TE endoscopic myotomies, 3 TV sleeve gastrectomies, and 18 TG sleeve gastrectomies. The average body mass indexes for those in the sleeve gastrectomy group was 42.1 kg/m(2) (TG route) and 40.6 kg/m(2) (TV route). There were no intraoperative complication and no conversions to standard laparoscopy during these procedures. The average hospital stay was 1-2 days. One patient who underwent TV cholecystectomy required an emergency department visit for nausea and vomiting. To date, 3 patients who underwent TV cholecystectomy have become pregnant and delivered normally. NOTES is safe, feasible, and reproducible with previous training in the laboratory and a consistent team at a high-volume center. Prospective randomized studies of a large patient population are necessary to assess long-term results. C1 [Horgan, Santiago; Jacobsen, Garth R.; Sandler, Bryan J.; Ferreres, Alberto; Ramamoorthy, Sonia; Savides, Thomas; Katagiri, Toshio; Dotai, Takayuki; Sedrak, Michael; Majid, Saniea F.; Nijhawan, Sheetal; Talamini, Mark A.] Univ Calif San Diego, Dept Surg, Div Minimally Invas Surg, San Diego, CA 92103 USA. [Meireles, Ozanan R.] Harvard Univ, Sch Med, Dept Surg, Div Minimally Invas Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Meireles, OR (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Minimally Invas Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM shorgan@ucsd.edu; omeireles@partners.org NR 16 TC 9 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD JUN PY 2013 VL 27 IS 6 BP 1872 EP 1880 DI 10.1007/s00464-012-2736-z PG 9 WC Surgery SC Surgery GA 150AF UT WOS:000319361900004 PM 23479251 ER PT J AU Lane, BF Wong-You-Cheong, JJ Javitt, MC Glanc, P Brown, DL Dubinsky, T Harisinghani, MG Harris, RD Khati, NJ Mitchell, DG Pandharipande, PV Pannu, HK Podrasky, AE Shipp, TD Siegel, CL Simpson, L Wall, DJ Zelop, CM AF Lane, Barton F. Wong-You-Cheong, Jade J. Javitt, Marcia C. Glanc, Phyllis Brown, Douglas L. Dubinsky, Theodore Harisinghani, Mukesh G. Harris, Robert D. Khati, Nadia J. Mitchell, Donald G. Pandharipande, Pari V. Pannu, Harpreet K. Podrasky, Anne E. Shipp, Thomas D. Siegel, Cary Lynn Simpson, Lynn Wall, Darci J. Zelop, Carolyn M. TI ACR Appropriateness Criteria (R) First Trimester Bleeding SO ULTRASOUND QUARTERLY LA English DT Article DE Appropriateness Criteria; vaginal bleeding; early pregnancy; ectopic pregnancy; threatened abortion; first trimester bleeding ID EARLY INTRAUTERINE PREGNANCY; GESTATIONAL TROPHOBLASTIC DISEASE; EMBRYONIC HEART-RATE; ECTOPIC PREGNANCY; INTRADECIDUAL SIGN; 1ST-TRIMESTER PREGNANCIES; INTERSTITIAL PREGNANCY; TRANSVAGINAL US; ENDOVAGINAL US; CORPUS-LUTEUM AB Vaginal bleeding is not uncommon in the first trimester of pregnancy. Ultrasound is the foremost modality for evaluating normal development of the gestational sac and embryo and for discriminating the causes of bleeding. While correlation with quantitative beta HCG and clinical presentation is essential, sonographic criteria permit diagnosis of failed pregnancies, ectopic pregnancy, gestational trophoblastic disease and spontaneous abortion. The American College of Radiology Appropriateness Criteria guidelines have been updated to incorporate recent data. A failed pregnancy may be diagnosed when there is absence of cardiac activity in an embryo exceeding 7 mm in crown rump length or absence of an embryo when the mean sac diameter exceeds 25 mm. In a stable patient with no intrauterine pregnancy and normal adnexae, close monitoring is advised. The diagnosis of ectopic pregnancy should be based on positive findings rather than on the absence of an intrauterine sac above a threshold level of beta HCG. Following abortion, ultrasound can discriminate retained products of conception from clot and arteriovenous fistulae. The American College of Radiology Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every two 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 [Lane, Barton F.; Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Javitt, Marcia C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Brown, Douglas L.; Wall, Darci J.] Mayo Clin, Rochester, MN USA. [Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA. [Harisinghani, Mukesh G.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Khati, Nadia J.] George Washington Univ Hosp, Washington, DC USA. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Podrasky, Anne E.] Baptist Hosp Miami, South Miami Ctr Women & Infants, Miami, FL USA. [Shipp, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Simpson, Lynn] Columbia Univ, New York, NY USA. [Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA. RP Wong-You-Cheong, JJ (reprint author), Univ Maryland, Med Ctr, Dept Diagnost Radiol, 22 S Greene St, Baltimore, MD 21201 USA. EM jwong@umm.edu NR 61 TC 2 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD JUN PY 2013 VL 29 IS 2 BP 91 EP 96 DI 10.1097/RUQ.0b013e31829158c2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 152AZ UT WOS:000319503100002 PM 23665531 ER PT J AU Gavin, J Gu, XK Gornik, HL Olin, JW Kim, ESH Mace, PD Gray, BH Bachrach, JM Jaff, MR McBane, RD Matsumoto, AH Kline-Rogers, E Froehlich, JB AF Gavin, Jordan Gu, Xiaokui Gornik, Heather L. Olin, Jeffrey W. Kim, Esther S. H. Mace, Pamela D. Gray, Bruce H. Bachrach, J. Michael Jaff, Michael R. McBane, Robert D. Matsumoto, Alan H. Kline-Rogers, Eva Froehlich, James B. TI Factors associated with delay in diagnosis of patients with fibromuscular dysplasia: A report from the United States Registry for Fibromuscular Dysplasia SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Gavin, Jordan; Gu, Xiaokui; Kline-Rogers, Eva; Froehlich, James B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gornik, Heather L.; Kim, Esther S. H.; Mace, Pamela D.] Cleveland Clin, Cleveland, OH 44106 USA. [Olin, Jeffrey W.] Mt Sinai, New York, NY USA. [Gray, Bruce H.] Greenville Hosp Syst, Greenville, SC USA. [Bachrach, J. Michael] North Cent Heart, Sioux Falls, SD USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McBane, Robert D.] Mayo Clin, Rochester, MN USA. [Matsumoto, Alan H.] Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD JUN PY 2013 VL 18 IS 3 BP 156 EP 157 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 153MS UT WOS:000319606800018 ER PT J AU van der Pluijm, W Di Eusanio, M Fattori, R Voehringer, M Myrmel, T Peterson, MD O'Gara, P Russo, MJ Evangelista, A Montgomery, DG Eagle, KA Isselbacher, EM Nienaber, CA AF van der Pluijm, Wouter Di Eusanio, Marco Fattori, Rossella Voehringer, Matthias Myrmel, Truls Peterson, Mark D. O'Gara, Patrick Russo, Mark J. Evangelista, Arturo Montgomery, Daniel G. Eagle, Kim A. Isselbacher, Eric M. Nienaber, Christoph A. TI Vessel involvement in Marfan syndrome patients SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [van der Pluijm, Wouter; Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Di Eusanio, Marco; Fattori, Rossella] Univ Hosp S Orsola, Bologna, Italy. [Voehringer, Matthias] Robert Bosch Krankenhaus, Stuttgart, Germany. [Myrmel, Truls] Univ Tromso Hosp, N-9012 Tromso, Norway. [Peterson, Mark D.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Russo, Mark J.] Univ Chicago, Chicago, IL 60637 USA. [Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Barcelona, Spain. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD JUN PY 2013 VL 18 IS 3 BP 161 EP 161 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 153MS UT WOS:000319606800027 ER PT J AU Weinberg, I Gu, XK Giri, J Olin, JW Froehlich, J Gornik, HL Rogers, KR Jaff, MR AF Weinberg, Ido Gu, Xiaokui Giri, Jay Olin, Jeffery W. Froehlich, James Gornik, Heather L. Rogers, Kevin R. Jaff, Michael R. TI Patterns of medication use in 615 patients with fibromuscular dysplasia. A report of the United States Registry for Fibromuscular Dysplasia SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Gu, Xiaokui; Froehlich, James] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Giri, Jay] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Olin, Jeffery W.] Mt Sinai New York, Zena & Michael Wiener Cardiovasc Inst, New York, NY USA. [Olin, Jeffery W.] Mt Sinai New York, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA. [Gornik, Heather L.] Case Western Reserve Univ, Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Gornik, Heather L.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Rogers, Kevin R.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD JUN PY 2013 VL 18 IS 3 BP 168 EP 168 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 153MS UT WOS:000319606800041 ER PT J AU Bergman, BG Greene, MC Hoeppner, BB Slaymaker, V Kelly, JF AF Bergman, B. G. Greene, M. C. Hoeppner, B. B. Slaymaker, V. Kelly, J. F. TI PSYCHIATRIC COMORBIDITY AND 12-STEP PARTICIPATION: A LONGITUDINAL INVESTIGATION OF TREATED YOUNG ADULTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Bergman, B. G.; Greene, M. C.; Hoeppner, B. B.; Slaymaker, V.; Kelly, J. F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 16A EP 16A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300022 ER PT J AU Labbe, AK Greene, MC Bergman, BG Hoeppner, BB Kelly, JF AF Labbe, A. K. Greene, M. C. Bergman, B. G. Hoeppner, B. B. Kelly, J. F. TI DOES AGE MATTER? THE EFFECT OF AGE COMPOSTION OF 12-STEP GROUPS ON YOUNG ADULT PARTICIPATION AND SUBSTANCE USE OUTCOME SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Labbe, A. K.; Greene, M. C.; Bergman, B. G.; Hoeppner, B. B.; Kelly, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Ctr Addict Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 16A EP 16A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300023 ER PT J AU Batki, SL Lasher, BA Metzler, T Heinz, AJ Herbst, E Waldrop, A Neylan, TC Kalapatapu, R AF Batki, S. L. Lasher, B. A. Metzler, T. Heinz, A. J. Herbst, E. Waldrop, A. Neylan, T. C. Kalapatapu, R. TI PREDICTORS OF OUTCOME IN A PILOT CONTROLLED TRIAL OF TOPIRAMATE FOR ALCOHOL DEPENDENCE IN VETERANS WITH PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Batki, S. L.; Lasher, B. A.; Metzler, T.; Heinz, A. J.; Herbst, E.; Waldrop, A.; Neylan, T. C.; Kalapatapu, R.] San Francisco VA Med Ctr, UCSF Dept Psychiat, Addict Res Program, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 17A EP 17A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300026 ER PT J AU Santos, GM Lasher, A Heinz, AJ Kalapatapu, R Herbst, E Metzler, T Waldrop, A Neylan, TC Tarasovsky, G Prathikanti, S Jatlow, P Batki, SL AF Santos, G-M Lasher, A. Heinz, A. J. Kalapatapu, R. Herbst, E. Metzler, T. Waldrop, A. Neylan, T. C. Tarasovsky, G. Prathikanti, S. Jatlow, P. Batki, S. L. TI URINARY ETHYL GLUCURONIDE AND ETHYL SULFATE TESTING TO EVALUATE THE EFFICACY OF TOPIRAMATE TREATMENT OF ALCOHOL DEPENDENCE IN VETERANS WITH PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Santos, G-M; Lasher, A.; Heinz, A. J.; Kalapatapu, R.; Herbst, E.; Metzler, T.; Waldrop, A.; Neylan, T. C.; Tarasovsky, G.; Prathikanti, S.; Jatlow, P.; Batki, S. L.] San Francisco VA Med Ctr, UCSF Dept Psychiat, Addict Res Program, San Francisco, CA 94121 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 19A EP 19A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300036 ER PT J AU Chen, S Charness, ME AF Chen, S. Charness, M. E. TI ANTAGONISM OF ALCOHOL INHIBITION OF L1-MEDIATED CELL ADHESION AND AXON OUTGROWTH IN CEREBELLAR GRANULE NEURONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, West Roxbury, MA 02132 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 49A EP 49A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300156 ER PT J AU Dou, X Menkari, CE Charness, ME AF Dou, X. Menkari, C. E. Charness, M. E. TI MULTIPLE KINASES REGULATE L1 SENSITIVITY TO ETHANOL THROUGH PHOSPHORYLATION OF THE L1 CYTOPLASMIC DOMAIN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Dou, X.; Menkari, C. E.; Charness, M. E.] Harvard Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 111A EP 111A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300403 ER PT J AU Below, MC Brandon, KO Goldman, MS AF Below, M. C. Brandon, K. O. Goldman, M. S. TI GROUPDRINK: SOCIAL FACILITATION OF DRINKING IN COLLEGE STUDENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Below, M. C.; Brandon, K. O.; Goldman, M. S.] Univ S Florida, Dept Psychol, Alcohol & Subst Use Res Inst, Tampa, FL 33620 USA. [Below, M. C.; Brandon, K. O.; Goldman, M. S.] VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 156A EP 156A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300584 ER PT J AU Wilhelm, CJ Hashimoto, JG Andrew, MR Roberts, ML Loftis, JM Wiren, KM AF Wilhelm, C. J. Hashimoto, J. G. Andrew, M. R. Roberts, M. L. Loftis, J. M. Wiren, K. M. TI PRO-INFLAMMATORY ACTIVATION FOLLOWING CHRONIC INTOXICATION IN FEMALE BUT NOT MALE MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 171A EP 171A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300641 ER PT J AU Rasmussen, DD Kincaid, CL Froehlich, JC AF Rasmussen, D. D. Kincaid, C. L. Froehlich, J. C. TI PRAZOSIN DECREASES ALCOHOL DRINKING DURING WITHDRAWAL IN RATS WITH A PROLONGED HISTORY OF VOLUNTARY HIGH ALCOHOL DRINKING AND DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 174A EP 174A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300656 ER PT J AU Rasmussen, DD Kincaid, CL Froehlich, JC AF Rasmussen, D. D. Kincaid, C. L. Froehlich, J. C. TI PRAZOSIN plus NALTREXONE DECREASES ALCOHOL DRINKING MORE EFFECTIVELY THAN DOES EITHER DRUG ALONE IN P RATS WITH HISTORY OF PROLONGED ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 175A EP 175A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998300657 ER PT J AU Cates, LN Nadav, T Crabbe, JC Phillips, TJ Roberts, AJ AF Cates, L. N. Nadav, T. Crabbe, J. C. Phillips, T. J. Roberts, A. J. TI FENOFIBRATE, BUT NOT TESAGLITAZAR, REDUCED ETHANOL DRINKING IN HIGH DRINKING-IN-THE-DARK MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Cates, L. N.; Nadav, T.; Crabbe, J. C.; Phillips, T. J.; Roberts, A. J.] Scripps Res Inst, La Jolla, CA 92037 USA. [Cates, L. N.; Nadav, T.; Crabbe, J. C.; Phillips, T. J.; Roberts, A. J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Cates, L. N.; Nadav, T.; Crabbe, J. C.; Phillips, T. J.; Roberts, A. J.] Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 245A EP 245A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301123 ER PT J AU Gubner, NR Phillips, TJ AF Gubner, N. R. Phillips, T. J. TI THE EFFECT OF NICOTINE IN COMBINATION WITH ETHANOL ON THE DEVELOPMENT OF BEHAVIORAL SENSITIZATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Gubner, N. R.; Phillips, T. J.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 248A EP 248A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301135 ER PT J AU Buck, KJ Walter, NAR Denmark, DL AF Buck, K. J. Walter, N. A. R. Denmark, D. L. TI SUPRAMOLECULAR ORGANIZATION OF MITOCHONDRIAL RESPIRATORY CHAIN COMPLEXES EXHIBITS STRAIN-DEPENDENCE IN C57BL6/J AND DBA/2J MOUSE BRAIN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR 97239 USA. Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 253A EP 253A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301153 ER PT J AU Leite-Morris, KA AF Leite-Morris, K. A. TI NEUROCHEMISTRY AND NEUROPHARMACOLOGY OF THE GABA-B RECEPTOR IN A RODENT MODEL OF ALCOHOL BINDGE DRINKING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Leite-Morris, K. A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Leite-Morris, K. A.] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. [Leite-Morris, K. A.] Boston Univ, Sch Med, Dept Expt Therapeut, Boston, MA 02118 USA. [Leite-Morris, K. A.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 255A EP 255A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301160 ER PT J AU Simpson, TL Stappenbeck, CA Luterek, JA Lehavot, K Kaysen, DL AF Simpson, T. L. Stappenbeck, C. A. Luterek, J. A. Lehavot, K. Kaysen, D. L. TI AN EVENT LEVEL EVALUATION OF THE INTERPLAY BETWEEN PTSD SYMPTOMS AND ALCOHOL CONSUMPTION AMONG INDIVIDUALS WITH COMORBID PTSD AND ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Simpson, T. L.; Stappenbeck, C. A.; Luterek, J. A.; Lehavot, K.; Kaysen, D. L.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 270A EP 270A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301221 ER PT J AU Lapham, GT Rubinsky, AD Hawkins, EJ Williams, EC Kivlahan, DJ Bradley, KA AF Lapham, G. T. Rubinsky, A. D. Hawkins, E. J. Williams, E. C. Kivlahan, D. J. Bradley, K. A. TI ANNUAL ALCOHOL SCREENING MAY NOT BE NECESSARY FOR NONDRINKERS WITH MULTIPLE PRIOR NEGATIVE SCREENS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Lapham, G. T.; Rubinsky, A. D.; Hawkins, E. J.; Williams, E. C.; Kivlahan, D. J.; Bradley, K. A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 286A EP 286A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301286 ER PT J AU Kelly, JF Hoeppner, BB AF Kelly, J. F. Hoeppner, B. B. TI DO MEN AND WOMEN BENEFIT DIFFERENTLY FROM ALCOHOLICS ANONYMOUS? A MODERATED MULTIPLE MEDIATION ANALYSIS IN A LARGE CLINICAL SAMPLE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 22-26, 2013 CL Orlando, FL SP Res Soc Alcoholism C1 [Kelly, J. F.; Hoeppner, B. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2013 VL 37 SU 2 SI SI BP 292A EP 292A PG 1 WC Substance Abuse SC Substance Abuse GA 145EU UT WOS:000318998301309 ER PT J AU Walkey, AJ Greiner, MA Heckbert, SR Jensen, PN Piccini, JP Sinner, MF Curtis, LH Benjamin, EJ AF Walkey, Allan J. Greiner, Melissa A. Heckbert, Susan R. Jensen, Paul N. Piccini, Jonathan P. Sinner, Moritz F. Curtis, Lesley H. Benjamin, Emelia J. TI Atrial fibrillation among Medicare beneficiaries hospitalized with sepsis: Incidence and risk factors SO AMERICAN HEART JOURNAL LA English DT Article ID ICD-9-CM CODES; UNITED-STATES; HEART; EPIDEMIOLOGY; OUTCOMES; SURGERY; STROKE; COHORT; GUIDELINES; ACCURACY AB Background Newly diagnosed atrial fibrillation (AF) during severe sepsis is associated with increased risks of in-hospital stroke and mortality. However, the prevalence, incidence, and risk factors associated with AF during the sepsis syndromes are unclear. Methods We identified patients with preexisting, newly diagnosed, or no AF in a nationally representative 5% sample of Medicare beneficiaries hospitalized with sepsis between 2004 and 2007. We identified multivariable-adjusted demographic and clinical characteristics associated with development of newly diagnosed AF during a sepsis hospitalization. Results A total of 60,209 beneficiaries had a sepsis hospitalization. Mean age was 80.2 years, 44.4% were men, and 83.1% were white. Atrial fibrillation occurred during 25.5% (95% CI 25.2-25.9) of sepsis hospitalizations, including 18.3% (18.0%-18.7%) with preexisting AF and 7.2% (7.0%-7.4%) with newly diagnosed AF. Patients with sepsis requiring intensive care had a greater risk of newly diagnosed AF (10.7%, 95% CI 10.3%-11.1%) compared with patients who did not require intensive care (4.4%, 4.2%-4.5%, P < .001). In multivariable analysis, factors associated with newly diagnosed AF during sepsis included older age, white race, acute organ dysfunction, intensive care unit admission, mechanical ventilation, right heart catheterization, diagnosis of endocarditis, and coronary artery bypass graft surgery. Cardiovascular comorbid conditions generally were not associated with increased risk for newly diagnosed AF during sepsis. Conclusions Atrial fibrillation is common among critically ill patients with sepsis. Acute factors, rather than preexisting cardiovascular comorbid conditions, are associated with increased risk for newly diagnosed AF during sepsis, suggesting that mechanisms of newly diagnosed AF during sepsis may differ from the general population of patients with AF. C1 [Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Pulm Ctr, Boston, MA 02118 USA. [Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, Boston, MA 02118 USA. [Greiner, Melissa A.; Piccini, Jonathan P.; Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Heckbert, Susan R.; Jensen, Paul N.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Piccini, Jonathan P.; Curtis, Lesley H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Sinner, Moritz F.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Sinner, Moritz F.] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA. RP Walkey, AJ (reprint author), 72 East Concord St,R-304, Boston, MA 02118 USA. EM alwalkey@bu.edu OI Walkey, Allan/0000-0003-4685-6894; Benjamin, Emelia/0000-0003-4076-2336 FU Bayer HealthCare; Boston Scientific; Johnson Johnson FX Dr Piccini reported receiving research support from Bayer HealthCare, Boston Scientific, and Johnson & Johnson and receiving personal income for participation on an advisory board for Sanofi-Aventis. Dr Curtis reported receiving research support from Johnson & Johnson. Drs Piccini and Curtis have made available online detailed listings of financial disclosures (http://www.dcri.duke.edu/about-us/conflict-of-interest/). No other disclosures were reported. NR 32 TC 26 Z9 26 U1 0 U2 9 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 JUN PY 2013 VL 165 IS 6 BP 949 EP + DI 10.1016/j.ahj.2013.03.020 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151DD UT WOS:000319439900017 PM 23708166 ER PT J AU Albayrak, O Putter, C Volckmar, AL Cichon, S Hoffmann, P Nothen, MM Jockel, KH Schreiber, S Wichmann, HE Faraone, SV Neale, BM Herpertz-Dahlmann, B Lehmkuhl, G Sinzig, J Renner, TJ Romanos, M Warnke, A Lesch, KP Reif, A Schimmelmann, BG Scherag, A Hebebrand, J Hinney, A AF Albayrak, Oezguer Puetter, Carolin Volckmar, Anna-Lena Cichon, Sven Hoffmann, Per Noethen, Markus M. Joeckel, Karl-Heinz Schreiber, Stefan Wichmann, H-Erich Faraone, Stephen V. Neale, Benjamin M. Herpertz-Dahlmann, Beate Lehmkuhl, Gerd Sinzig, Judith Renner, Tobias J. Romanos, Marcel Warnke, Andreas Lesch, Klaus-Peter Reif, Andreas Schimmelmann, Benno G. Scherag, Andre Hebebrand, Johannes Hinney, Anke CA Psychiat GWAS Consortium ADHD Subg TI Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE body mass index; inattention; genetic risk factor; genome wide association study; weight regulation ID GENOME-WIDE ASSOCIATION; DEFICIT HYPERACTIVITY DISORDER; FACTOR GENE BDNF; BODY-MASS INDEX; NEUROTROPHIC FACTOR; CONDUCT DISORDER; GROWTH DEFICITS; CHILDREN; ADHD; ADOLESCENTS AB Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; P=3.4x104; Pcorr=0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P=7.2x104; Pcorr=0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity. (c) 2013 Wiley Periodicals, Inc. C1 [Albayrak, Oezguer; Volckmar, Anna-Lena; Hebebrand, Johannes; Hinney, Anke] Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychotherapy &, LVR Klinikum Essen, D-45147 Essen, Germany. [Puetter, Carolin; Joeckel, Karl-Heinz; Scherag, Andre] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, D-45147 Essen, Germany. [Cichon, Sven] Res Ctr Julich, Struct & Funct Org Brain, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, Sven; Hoffmann, Per; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Hoffmann, Per; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Schreiber, Stefan] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Popgen Study Grp, Kiel, Germany. [Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiologyl, KORA Study Grp, Munich, Germany. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Herpertz-Dahlmann, Beate] Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat, Aachen, Germany. [Lehmkuhl, Gerd; Sinzig, Judith] Univ Cologne, Dept Child & Adolescent Psychiat, Cologne, Germany. [Sinzig, Judith] LVR Linikum Bonn, Dept Child & Adolescent Psychiat & Psychotherapy, Bonn, Germany. [Renner, Tobias J.; Romanos, Marcel; Warnke, Andreas] Univ Wurzburg, Dept Child & Adolescent Psychiat, Wurzburg, Germany. [Romanos, Marcel] Univ Munich, Dept Child & Adolescent Psychiat, Munich, Germany. [Lesch, Klaus-Peter; Reif, Andreas] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. [Schimmelmann, Benno G.] Univ Bern, Univ Hosp Child & Adolescent Psychiat, CH-3012 Bern, Switzerland. RP Albayrak, O (reprint author), Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychotherapy &, LVR Klinikum Essen, Wickenburgstr 21, D-45147 Essen, Germany. EM oezguer.albayrak@uni-due.de RI Romanos, Marcel/D-7695-2017; Hinney, Anke/D-6953-2011; Renner, Tobias/I-2120-2013; Lesch, Klaus-Peter/J-4906-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Schreiber, Stefan/B-6748-2008 OI Sinzig, Judith/0000-0002-3693-3318; Hinney, Anke/0000-0001-5659-0706; Scherag, Andre/0000-0002-9406-4704; Nothen, Markus/0000-0002-8770-2464; Faraone, Stephen/0000-0002-9217-3982; Lesch, Klaus-Peter/0000-0001-8348-153X; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Schreiber, Stefan/0000-0003-2254-7771 FU German Ministry for Education and Research (National Genome Research Net plus) [01GS0820, 01KU0903]; German Research Foundation [DFG HE 1446/9-1, KFO 125/1-1, SCHA 542/10-2, ME 1923/5-1, ME 1923/5-3]; European Community [245009]; US National of Institute of Health [R13MH059126, R01MH62873, R01MH081803, K23MH066275]; Children's Hospital of Philadelphia [UL1-RR-024134]; NHMRC (Australia); Sidney Sax Public Health Fellowship [443036] FX Grant sponsor: German Ministry for Education and Research (National Genome Research Net plus); Grant numbers: 01GS0820, 01KU0903; Grant sponsor: German Research Foundation; Grant numbers: DFG HE 1446/9-1, KFO 125/1-1, SCHA 542/10-2, ME 1923/5-1, ME 1923/5-3; Grant sponsor: European Community's Seventh Framework Programme (FP7/2007-2013); Grant number: 245009; Grant sponsor: US National of Institute of Health Grants; Grant numbers: R13MH059126, R01MH62873, R01MH081803, K23MH066275; Grant sponsor: Children's Hospital of Philadelphia; Grant number: UL1-RR-024134; Grant sponsor: NHMRC (Australia) and Sidney Sax Public Health Fellowship; Grant number: 443036. NR 78 TC 22 Z9 22 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2013 VL 162B IS 4 BP 295 EP 305 DI 10.1002/ajmg.b.32144 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 150UF UT WOS:000319416100001 PM 23533005 ER PT J AU Pato, MT Sobell, JL Medeiros, H Abbott, C Sklar, BM Buckley, PF Bromet, EJ Escamilla, MA Fanous, AH Lehrer, DS Macciardi, F Malaspina, D McCarroll, SA Marder, SR Moran, J Morley, CP Nicolini, H Perkins, DO Purcell, SM Rapaport, MH Sklar, P Smoller, JW Knowles, JA Pato, CN AF Pato, Michele T. Sobell, Janet L. Medeiros, Helena Abbott, Colony Sklar, Brooke M. Buckley, Peter F. Bromet, Evelyn J. Escamilla, Michael A. Fanous, Ayman H. Lehrer, Douglas S. Macciardi, Fabio Malaspina, Dolores McCarroll, Steve A. Marder, Stephen R. Moran, Jennifer Morley, Christopher P. Nicolini, Humberto Perkins, Diana O. Purcell, Shaun M. Rapaport, Mark H. Sklar, Pamela Smoller, Jordan W. Knowles, James A. Pato, Carlos N. CA Genomic Psychiat Cohort Consortium TI The genomic psychiatry cohort: Partners in discovery SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetic epidemiology; schizophrenia; bipolar disorder; repository ID BIPOLAR-DISORDER; DIAGNOSTIC INTERVIEW; WIDE ASSOCIATION; COMMON VARIANTS; SCHIZOPHRENIA; RELIABILITY; RISK; FEATURES; LINKAGE; SYSTEM AB The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested casecontrol studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants. (c) 2013 Wiley Periodicals, Inc. C1 [Pato, Michele T.; Sobell, Janet L.; Medeiros, Helena; Abbott, Colony; Sklar, Brooke M.; Knowles, James A.; Pato, Carlos N.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Buckley, Peter F.] Georgia Regents Univ, Dept Psychiat, Augusta, GA USA. [Bromet, Evelyn J.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Escamilla, Michael A.] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, El Paso, TX USA. [Fanous, Ayman H.] Vet Adm Med Ctr, Dept Psychiat, Washington, DC 20422 USA. [Lehrer, Douglas S.] Wright State Univ, Dept Psychiat, Dayton, OH 45435 USA. [Macciardi, Fabio] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. [Malaspina, Dolores] NYU, Dept Psychiat, New York, NY 10016 USA. [McCarroll, Steve A.; Moran, Jennifer] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [McCarroll, Steve A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Marder, Stephen R.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Morley, Christopher P.] SUNY Upstate Med Univ, Dept Family Med, Syracuse, NY 13210 USA. [Morley, Christopher P.] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA. [Morley, Christopher P.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Nicolini, Humberto] Carracci Med Grp, Mexico City, DF, Mexico. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genome Res, Boston, MA 02114 USA. [Rapaport, Mark H.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Smoller, Jordan W.] Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. RP Pato, CN (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, 2250 Alcazar St, Los Angeles, CA 90033 USA. RI Macciardi, Fabio/N-3768-2014; Morley, Christopher P/K-1907-2014; OI Macciardi, Fabio/0000-0003-0537-4266; Lehrer, Douglas/0000-0002-3014-9119; Morley, Christopher P/0000-0003-0185-7148; Nicolini, Humberto/0000-0003-2494-0067; Moran, Jennifer/0000-0002-5664-4716 FU NIH [MH085548, MH085542]; Stanley Center for Psychiatric Research; Broad Institute of MIT; Broad Institute of Harvard FX Grant sponsor: NIH; Grant numbers: MH085548; MH085542; Grant sponsor: Stanley Center for Psychiatric Research; Grant sponsor: Broad Institute of MIT and Harvard. NR 35 TC 12 Z9 12 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2013 VL 162B IS 4 BP 306 EP 312 DI 10.1002/ajmg.b.32160 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 150UF UT WOS:000319416100002 PM 23650244 ER PT J AU Stewart, SE Mayerfeld, C Arnold, PD Crane, JR O'Dushlaine, C Fagerness, JA Yu, D Scharf, JM Chan, E Kassam, F Moya, PR Wendland, JR Delorme, R Richter, MA Kennedy, JL Veenstra-VanderWeele, J Samuels, J Greenberg, BD McCracken, JT Knowles, JA Fyer, AJ Rauch, SL Riddle, MA Grados, MA Bienvenu, OJ Cullen, B Wang, Y Shugart, YY Piacentini, J Rasmussen, S Nestadt, G Murphy, DL Jenike, MA Cook, EH Pauls, DL Hanna, GL Mathews, CA AF Stewart, S. E. Mayerfeld, C. Arnold, P. D. Crane, J. R. O'Dushlaine, C. Fagerness, J. A. Yu, D. Scharf, J. M. Chan, E. Kassam, F. Moya, P. R. Wendland, J. R. Delorme, R. Richter, M. A. Kennedy, J. L. Veenstra-VanderWeele, J. Samuels, J. Greenberg, B. D. McCracken, J. T. Knowles, J. A. Fyer, A. J. Rauch, S. L. Riddle, M. A. Grados, M. A. Bienvenu, O. J. Cullen, B. Wang, Y. Shugart, Y. Y. Piacentini, J. Rasmussen, S. Nestadt, G. Murphy, D. L. Jenike, M. A. Cook, E. H. Pauls, D. L. Hanna, G. L. Mathews, C. A. TI Meta-analysis of association between obsessive-compulsive disorder and the 3 ' region of neuronal glutamate transporter gene SLC1A1 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive-compulsive disorder; OCD; candidate gene; meta-analysis; SLC1A1; glutamate ID COMPLEX SEGREGATION ANALYSIS; FAMILY-BASED ASSOCIATION; OPEN-LABEL TRIAL; GENDER-RELATED DIFFERENCES; GENOME-WIDE ASSOCIATION; OCD-LIKE BEHAVIORS; PEDIATRIC PROBANDS; LINKAGE ANALYSIS; CANDIDATE GENE; COMORBIDITY AB The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3 end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P=0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N=358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P=0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD. (c) 2013 Wiley Periodicals, Inc. C1 [Stewart, S. E.; Rauch, S. L.; Jenike, M. A.] McLean Hosp, Belmont, MA 02178 USA. [Stewart, S. E.; Rauch, S. L.; Jenike, M. A.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stewart, S. E.; Mayerfeld, C.; Crane, J. R.; Fagerness, J. A.; Yu, D.; Scharf, J. M.; Rauch, S. L.; Murphy, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Stewart, S. E.; Scharf, J. M.; Jenike, M. A.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, S. E.; Chan, E.; Kassam, F.] Univ British Columbia, Vancouver, BC V5Z 4H4, Canada. [Stewart, S. E.] British Columbia Mental Hlth & Addict Res Inst Va, Vancouver, BC, Canada. [Arnold, P. D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Arnold, P. D.; Richter, M. A.; Kennedy, J. L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [O'Dushlaine, C.; Scharf, J. M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Boston, MA USA. [Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scharf, J. M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Moya, P. R.; Wendland, J. R.; Shugart, Y. Y.; Murphy, D. L.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Wendland, J. R.] F Hoffmann La Roche & Co Ltd, Pharma Res & Early Dev, CNS Clin Biomarker Grp, CH-4002 Basel, Switzerland. [Delorme, R.] Robert Debre Hosp, AP HP, Dept Child & Adolescent Psychiat, INSERM,U955, Paris, France. [Delorme, R.] Inst Mondor Rech Biomed, Creteil, France. [Delorme, R.] French Natl Sci Fdn, Fdn Fondamental, Paris, France. [Richter, M. A.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Clin OCD & Related Disorders, Toronto, ON M4N 3M5, Canada. [Kennedy, J. L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Lab, Toronto, ON, Canada. [Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN USA. [Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Pediat, Nashville, TN USA. [Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Pharmacol, Nashville, TN USA. [Veenstra-VanderWeele, J.] Vanderbilt Brain Inst, Nashville, TN USA. [Samuels, J.; Riddle, M. A.; Grados, M. A.; Bienvenu, O. J.; Cullen, B.; Wang, Y.; Rasmussen, S.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Knowles, J. A.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90024 USA. [Fyer, A. J.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rauch, S. L.] Partners Psychiat & Mental Hlth, Belmont, MA USA. [Cook, E. H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. [Hanna, G. L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Mathews, C. A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Stewart, SE (reprint author), Univ British Columbia, Dept Psychiat, A3-118,West 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM evelyn.stewart@ubc.ca RI Stewart, Evelyn/K-6961-2014; Veenstra-VanderWeele, Jeremy/K-1935-2015; OI Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Samuels, Jack/0000-0002-6715-7905; Hanna, Gregory/0000-0002-0742-6990; Stewart, S. Evelyn/0000-0002-0994-6383 FU Eli Lilly Canada Inc; Ontario Mental Health Foundation; Obsessive-Compulsive Foundation; Novartis; Seaside Therapeutics; Roche; Forest; Cyberonics; Medtronic FX Grant sponsor: Eli Lilly Canada Inc, Ontario Mental Health Foundation and the Obsessive-Compulsive Foundation; Grant sponsor: Novartis, Seaside Therapeutics, Roche, and Forest; Grant sponsor: Cyberonics and Medtronic. NR 87 TC 27 Z9 28 U1 1 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2013 VL 162B IS 4 BP 367 EP 379 DI 10.1002/ajmg.b.32137 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 150UF UT WOS:000319416100005 PM 23606572 ER PT J AU Tirumani, SH Shinagare, AB Sakellis, C Saboo, SS Jagannathan, JP Krajewski, KM Ramaiya, NH AF Tirumani, Sree Harsha Shinagare, Atul B. Sakellis, Christopher Saboo, Sachin S. Jagannathan, Jyothi P. Krajewski, Katherine M. Ramaiya, Nikhil H. TI Merkel Cell Carcinoma: A Primer for the Radiologist SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE Merkel cell carcinoma; PET/CT; sentinel lymph node biopsy ID OF-THE-LITERATURE; SINGLE INSTITUTION; CASE SERIES; RADIATION; SKIN; DIAGNOSIS; HEAD; NECK; CHEMOTHERAPY; MANAGEMENT AB OBJECTIVE. Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor. The purpose of this review is to provide a comprehensive description of the staging, workup, treatment, and follow-up of MCC. CONCLUSION. Sentinel lymph node mapping and PET/CT are the cornerstones of staging of MCC. MCC is a radiosensitive tumor, and hence radiotherapy plays a major role in its management. Close follow-up with PET/CT helps in detecting recurrences of MCC. C1 [Tirumani, Sree Harsha; Sakellis, Christopher; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Shinagare, Atul B.; Sakellis, Christopher; Saboo, Sachin S.; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 56 TC 7 Z9 7 U1 1 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 JUN PY 2013 VL 200 IS 6 BP 1186 EP 1196 DI 10.2214/AJR.12.9884 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151GC UT WOS:000319447700025 PM 23701052 ER PT J AU Kang, SK Huang, WC Lee, VS Chandarana, H AF Kang, Stella K. Huang, William C. Lee, Vivian S. Chandarana, Hersh TI MR Renographic Measurement of Renal Function in Patients Undergoing Partial Nephrectomy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE MR renography; partial nephrectomy; renal function ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CONTRAST-ENHANCED MRI; RADICAL NEPHRECTOMY; CELL CARCINOMA; UNITED-STATES; RISK-FACTORS; DYNAMIC MRI; MORTALITY; MODEL AB OBJECTIVE. The purpose of this review is to describe the role of functional renal MRI, or MR renography, in the care of patients with renal masses undergoing partial nephrectomy. CONCLUSION. MR renography can be used to monitor renal functional outcome for patients undergoing partial nephrectomy and may help guide patient selection in this population with elevated risk of chronic kidney disease. C1 [Kang, Stella K.; Chandarana, Hersh] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA. [Huang, William C.] NYU, Langone Med Ctr, Dept Urol, New York, NY USA. [Lee, Vivian S.] Univ Utah Hlth Sci, Dept Radiol, Salt Lake City, UT USA. RP Kang, SK (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, White Bldg,Rm 270,55 Fruit St, Boston, MA 02114 USA. EM skang4@partners.org RI Kang, Stella/O-7003-2015; OI Chandarana, Hersh/0000-0002-6807-4589; Kang, Stella/0000-0003-2402-3787; Huang, William/0000-0001-5261-0650 FU NIDDK NIH HHS [R01 DK063183, R01 DK088375] NR 41 TC 2 Z9 2 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 JUN PY 2013 VL 200 IS 6 BP 1204 EP 1209 DI 10.2214/AJR.12.10276 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151GC UT WOS:000319447700027 PM 23701054 ER PT J AU Kreydin, EI Barrisford, GW Feldman, AS Preston, MA AF Kreydin, Evgeniy I. Barrisford, Glen W. Feldman, Adam S. Preston, Mark A. TI Testicular Cancer: What the Radiologist Needs to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT; diagnosis; diagnostic performance; evidence-based medicine; MRI; staging; testicular cancer; testis cancer ID GERM-CELL TUMORS; POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-PRACTICE GUIDELINES; LYMPH-NODE METASTASES; EUROPEAN CONSENSUS CONFERENCE; TESTIS CANCER; STAGE-I; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; VIABLE TUMOR AB OBJECTIVE. The purpose of this article is to review current imaging techniques and evolving technologies that are being used for detection and management of testicular cancer. CONCLUSION. The primary goal of cancer imaging is accurate disease characterization at diagnosis and through all stages of management. Knowledge of the disease and diagnostic performance characteristics of each technique is critical to identify the appropriate modality for staging disease and to monitor for treatment response and recurrence that may dictate further intervention. C1 [Kreydin, Evgeniy I.; Barrisford, Glen W.; Feldman, Adam S.; Preston, Mark A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Preston, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM mpreston1@partners.org NR 65 TC 7 Z9 8 U1 0 U2 10 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 JUN PY 2013 VL 200 IS 6 BP 1215 EP 1225 DI 10.2214/AJR.12.10319 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151GC UT WOS:000319447700029 PM 23701056 ER PT J AU Uppot, RN Gervais, DA AF Uppot, Raul N. Gervais, Debra A. TI Imaging-Guided Adrenal Tumor Ablation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE cryoablation; functioning adrenal tumors; microwave ablation; radiofrequency ablation; renal tumors ID PERCUTANEOUS RADIOFREQUENCY ABLATION; IRREVERSIBLE ELECTROPORATION; METASTATIC PHEOCHROMOCYTOMA; MICROWAVE ABLATION; ADRENOCORTICAL CARCINOMA; RENAL TUMORS; NEOPLASMS; CRYOABLATION; EXPERIENCE; HYPERTENSION AB OBJECTIVE. The purpose of this review is to describe the indications for and approach to imaging-guided ablation of the adrenal gland. CONCLUSION. Imaging-guided radiofrequency ablation of the adrenal glands is an effective procedure in the local control of primary or metastatic adrenal malignancy and is an alternative minimally invasive therapy for functioning adrenal tumors. Potential complications of hypertensive crises can be managed by preprocedure administration of alpha- and beta-blockers in coordination with the anesthesiology department. C1 [Uppot, Raul N.; Gervais, Debra A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Gervais, Debra A.] Harvard Univ, Sch Med, Div Pediat Imaging, Dept Radiol, Boston, MA 02114 USA. RP Uppot, RN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM ruppot@partners.org NR 49 TC 9 Z9 9 U1 0 U2 6 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 JUN PY 2013 VL 200 IS 6 BP 1226 EP 1233 DI 10.2214/AJR.12.10328 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151GC UT WOS:000319447700030 PM 23701057 ER PT J AU Elmi, A Hedgire, SS Pargaonkar, V Cao, K McDermott, S Harisinghani, M AF Elmi, Azadeh Hedgire, Sandeep S. Pargaonkar, Vivek Cao, Kai McDermott, Shaunagh Harisinghani, Mukesh TI Is Early Colonoscopy Beneficial in Patients With CT-Diagnosed Diverticulitis? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cancer; colon; CT; diverticular disease; diverticulitis; endoscopy ID COLORECTAL-CANCER; COLON-CANCER; SIGMOID DIVERTICULITIS; CONTRAST ENEMA; HELICAL CT; DISEASE; DIFFERENTIATION; RISK AB OBJECTIVE. The purpose of this study was to establish CT criteria as an indication for colonoscopy in patients with acute diverticulitis. MATERIALS AND METHODS. The study was composed of patients diagnosed with acute diverticulitis on contrast-enhanced CT (CECT) from January 2000 to December 2004. Patients without subsequent colonoscopy were excluded. Findings on CT were correlated with patient outcomes over follow-up. Sensitivity, specificity, and predictive values of the imaging parameters for prediction of colon cancer were calculated. Outcomes were also compared between men and women. RESULTS. Of 1034 patients with a CT diagnosis of diverticulitis, 402 (235 women and 167 men; mean age, 63.3 years) had available endoscopic colonic evaluation after CECT. The mean follow-up was 5.3 years. Seventy-eight patients had polyps (71% adenomatous) and nine patients (2.2%) were diagnosed with colon cancer (seven women, two men). The odds ratio for diagnosis of colon cancer was 23.35 in patients with mesenteric or retroperitoneal lymphnodes, 4.67 for abscess, and 24.43 in patients with obstruction and localized mass reported on CT. A significant correlation was found between the location of diverticulitis and cancer (p < 0.001). The diagnosis of cancer was made within 6 months from the date of CECT in eight patients. The odds of cancer were 2.5 times higher in women. CONCLUSION. On the basis of the significant correlation of complicated diverticulitis or presence of lymph nodes with new diagnoses of colon cancer, we recommend early colonoscopy in patients with wall thickness more than 6 mm, abscess, obstruction, or lymph nodes seen on CECT. C1 [Elmi, Azadeh; Hedgire, Sandeep S.; Pargaonkar, Vivek; Cao, Kai; McDermott, Shaunagh; Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Elmi, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM aelmi@partners.org NR 23 TC 18 Z9 18 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 JUN PY 2013 VL 200 IS 6 BP 1269 EP 1274 DI 10.2214/AJR.12.9539 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151GC UT WOS:000319447700036 PM 23701063 ER PT J AU Pandharipande, PV Eisenberg, JD Avery, LL Gunn, ML Kang, SK Megibow, AJ Turan, EA Harvey, HB Kong, CY Dowling, EC Halpern, EF Donelan, K Gazelle, GS AF Pandharipande, Pari V. Eisenberg, Jonathan D. Avery, Laura L. Gunn, Martin L. Kang, Stella K. Megibow, Alec J. Turan, Ekin A. Harvey, H. Benjamin Kong, Chung Yin Dowling, Emily C. Halpern, Elkan F. Donelan, Karen Gazelle, G. Scott TI How Radiation Exposure Histories Influence Physician Imaging Decisions: A Multicenter Radiologist Survey Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; physician decision making; radiation-induced cancer risks; survey research ID SUNK COST; IONIZING-RADIATION; QUALITY-ASSURANCE; CANCER-RISKS AB OBJECTIVE. The purpose of this article is to evaluate the influence of patient radiation exposure histories on radiologists' imaging decisions. MATERIALS AND METHODS. We conducted a physician survey study in three academic medical centers. Radiologists were asked to make an imaging recommendation for a hypothetical patient with a history of multiple CT scans. We queried radiologists' decision making, evaluating whether they incorporated cancer risks from previous imaging, reported acceptance (or rejection) of the linear no-threshold model, and understood linear no-threshold model implications in this setting. Consistency between radiologists' decisions and their linear no-threshold model beliefs was evaluated; those acting in accordance with the linear no-threshold model were expected to disregard previously incurred cancer risks. A Fisher exact test was used to verify the generalizability of results across institutions and training levels (residents, fellows, and attending physicians). RESULTS. Fifty-six percent (322/578) of radiologists completed the survey. Most (92% [295/322]) incorporated risks from the patient's exposure history during decision making. Most (61% [196/322]) also reported acceptance of the linear no-threshold model. Fewer (25% [79/322]) rejected the linear no-threshold model; 15% (47/322) could not judge. Among radiologists reporting linear no-threshold model acceptance or rejection, the minority (36% [98/275]) made decisions that were consistent with their linear no-threshold model beliefs. This finding was not statistically different across institutions (p = 0.070) or training levels (p = 0.183). Few radiologists (4% [13/322]) had an accurate understanding of linear no-threshold model implications. CONCLUSION. Most radiologists, when faced with patient exposure histories, make decisions that contradict their self-reported acceptance of the linear no-threshold model and the linear no-threshold model itself. These findings underscore a need for educational initiatives. C1 [Pandharipande, Pari V.; Eisenberg, Jonathan D.; Turan, Ekin A.; Harvey, H. Benjamin; Kong, Chung Yin; Dowling, Emily C.; Halpern, Elkan F.; Donelan, Karen; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Pandharipande, Pari V.; Eisenberg, Jonathan D.; Avery, Laura L.; Kang, Stella K.; Turan, Ekin A.; Kong, Chung Yin; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Pandharipande, Pari V.; Avery, Laura L.; Harvey, H. Benjamin; Kong, Chung Yin; Halpern, Elkan F.; Donelan, Karen; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Eisenberg, Jonathan D.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA. [Gunn, Martin L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Kang, Stella K.; Megibow, Alec J.] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Fl, Boston, MA 02114 USA. EM pari@mgh-ita.org RI Kang, Stella/O-7003-2015; OI Gunn, Martin/0000-0001-9879-8660 FU National Cancer Institute [K07CA133097, K25CA133141]; Medical Imaging and Technology Alliance; GE Healthcare FX This study was supported in part by the National Cancer Institute (awards K07CA133097 to P. V. Pandharipande and K25CA133141 to C. Y. Kong). The research content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. P. V. Pandharipande receives research funding from the Medical Imaging and Technology Alliance for unrelated research. E. F. Halpern is a consultant for Hologic. K. Donelan receives research funding from GE Healthcare and from the Medical Imaging and Technology Alliance for unrelated research. G. S. Gazelle is a consultant for GE Healthcare. NR 19 TC 15 Z9 15 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2013 VL 200 IS 6 BP 1275 EP 1283 DI 10.2214/AJR.12.10011 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151GC UT WOS:000319447700037 PM 23701064 ER PT J AU Caplan, L Clegg, DO Inman, RD AF Caplan, Liron Clegg, Daniel O. Inman, Robert D. TI Ankylosing Spondylitis Clinical Registries: Principles, Practices and Possibilities SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the SPondyloArthritis-Research-and-Treatment-Network (SPARTAN)-Group-for-Research-and-Assessment-of-Psoriasis-and-Psoriatic-A rthritis (GRAPPA) CY JUL 27-28, 2012 CL Portland, OR SP SPondyloArthritis Res & Treatment Network (SPARTAN), Grp Res & Assessment Psoriasis & Psoriat Arthrit (GRAPPA) DE Clinical registry; Spondyloathritis; Ankylosing spondylitis AB The need for a rigorously developed longitudinal registry of patients with spondyloarthritis (SpA) is clear and urgent. Like randomized controlled trials, registries rely on a prospective, systematic protocol-driven approach to data acquisition to assess outcomes for a prescribed cohort of patients. Registries seek to capture large numbers of patients across large geographic zones and can serve as a valuable resource for patient advocacy, patient education and support, incidence and prevalence, and broad demographic profiles. Building on 3 existing registries the Prospective Study of Outcomes in Ankylosing Spondylitis, the Program to Understand the Longterm Outcomes of Spondyloarthritis (PULSAR) and the University Health Network Spondyloarthritis Program-these registries and the Spondylitis Association of America propose to form a combined registry of North American SpA patients. The combined registry would, ideally, complement ongoing clinical goals and improve patient care. C1 [Caplan, Liron] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. [Clegg, Daniel O.] Univ Utah, Sch Med, George E Whalen Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT USA. [Inman, Robert D.] Univ Toronto, Toronto, ON, Canada. RP Clegg, DO (reprint author), Univ Utah Hlth Care, 50 North Med Dr, Salt Lake City, UT 84132 USA. EM daniel.clegg@hsc.utah.edu NR 1 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JUN PY 2013 VL 345 IS 6 BP 437 EP 439 DI 10.1097/MAJ.0b013e3182937335 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 151CH UT WOS:000319437700005 PM 23841118 ER PT J AU Melo, MFV Eikermann, M AF Melo, Marcos F. Vidal Eikermann, Matthias TI Protect the Lungs during Abdominal Surgery It May Change the Postoperative Outcome SO ANESTHESIOLOGY LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; LOWER TIDAL VOLUMES; MECHANICAL VENTILATION; INJURY; SURFACTANT; PRESSURE; MODEL C1 [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA USA. [Eikermann, Matthias] Univ Klinikum Essen, Univ Duisburg Essen, Klin Anasthesiol & Intensivmed, Essen, Germany. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. EM meikermann@partners.org NR 16 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2013 VL 118 IS 6 BP 1254 EP 1257 DI 10.1097/ALN.0b013e3182910309 PG 4 WC Anesthesiology SC Anesthesiology GA 149PZ UT WOS:000319334700005 PM 23535504 ER PT J AU Brueckmann, B Villa-Uribe, JL Bateman, BT Rosse-Sundrup, MG Hess, DR Schlett, CL Eikermann, M AF Brueckmann, Britta Villa-Uribe, Jose L. Bateman, Brian T. Rosse-Sundrup, Martina G. Hess, Dean R. Schlett, Christopher L. Eikermann, Matthias TI Development and Validation of a Score for Prediction of Postoperative Respiratory Complications SO ANESTHESIOLOGY LA English DT Article ID MAJOR NONCARDIAC SURGERY; OBSTRUCTIVE SLEEP-APNEA; TRACHEAL INTUBATION; UNPLANNED INTUBATION; RISK STRATIFICATION; FAILURE; MORTALITY; OUTCOMES; SYSTEM; INDEX AB Background: Postoperative respiratory failure is associated with increased morbidity and mortality, as well as high costs of hospital care. Methods: Using electronic anesthesia records, billing data, and chart review, the authors developed and validated a score predicting reintubation in the hospital after primary extubation in the operating room, leading to unplanned mechanical ventilation within the first 3 postoperative days. Using multivariable logistic regression analysis, independent predictors were determined and a score postulated and validated. Results: In the entire cohort (n = 33,769 surgical cases within 29,924 patients), reintubation occurred in 137 cases (0.41%). Of those, 16%, (n = 22) died subsequently, whereas the mortality in patients who were not reintubated was 0.26% (P < 0.0001). Independent predictors for reintubation were: American Society of Anesthesiologist Score 3 or more, emergency surgery, high-risk surgical service, history of congestive heart failure, and chronic pulmonary disease. A point value of 3, 3, 2, 2, and 1 were assigned to these predictors, respectively, based on their beta coefficient in the predictive model. The score yielded a calculated area under the curve of 0.81, whereas each point increment was associated with a 1.7-fold (odds ratio: 1.72 [95% CI, 1.55-1.91]) increase in the odds for reintubation in the training dataset. Using the validation dataset (n = 16,884), the score had an area under the curve of 0.80 and similar estimated probabilities for reintubation. Conclusion: The authors developed and validated a score for the prediction of postoperative respiratory complications, a simple, 11-point score that can be used preoperatively by anesthesiologists to predict severe postoperative respiratory complications. C1 [Brueckmann, Britta; Villa-Uribe, Jose L.; Bateman, Brian T.; Rosse-Sundrup, Martina G.; Hess, Dean R.; Schlett, Christopher L.; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02115 USA. EM meiker-mann@partners.org NR 31 TC 46 Z9 49 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2013 VL 118 IS 6 BP 1276 EP 1285 DI 10.1097/ALN.0b013e318293065c PG 10 WC Anesthesiology SC Anesthesiology GA 149PZ UT WOS:000319334700009 PM 23571640 ER PT J AU Bakaeen, FG Chu, D Kelly, RF Ward, HB Jessen, ME Chen, GJ Petersen, NJ Holman, WL AF Bakaeen, Faisal G. Chu, Danny Kelly, Rosemary F. Ward, Herbert B. Jessen, Michael E. Chen, G. John Petersen, Nancy J. Holman, William L. TI Performing Coronary Artery Bypass Grafting Off-Pump May Compromise Long-Term Survival in a Veteran Population SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-30, 2013 CL Los Angeles, CA SP Soc Thorac Surg ID ON-PUMP; RANDOMIZED-TRIAL; REDUCE MORBIDITY; CARDIAC-SURGERY; OUTCOMES; REVASCULARIZATION; MORTALITY; METAANALYSIS; STROKE; PATENCY AB Background. There are ample data regarding the short-term outcomes of on-pump and off-pump coronary artery bypass grafting (CABG), but little is known about the long-term survival associated with these approaches. Methods. Using the Veterans Affairs (VA) Continuous Improvement in Cardiac Surgery Program, we identified all VA patients (n = 65,097) who underwent primary isolated CABG from October 1997 to April 2011. The primary outcome measure was all-cause mortality. Age, 17 preoperative risk factors, and year of operation were used to calculate propensity scores for each patient. A greedy-match algorithm using the propensity scores matched 8,911 off-pump with 26,733 on-pump patients. Survival functions were estimated by the Kaplan-Meier method and compared by using the log-rank test. Results. In the complete cohort, off-pump was used in 11,629 of 65,097 (17.9%) operations. For the matched cohort, the median follow-up was 6.7 years (interquartile range, 3.72 to 9.35 years). Risk-adjusted mortality did not differ significantly between the off-pump and on-pump groups at 1 year (4.67% vs 4.78%; risk ratio [RR], 0.98; 95% confidence interval [CI], 0.88 to 1.09) or 3 years (9.21% vs 8.89%; RR, 1.04; 95% CI, 0.96 to 1.12). However, risk-adjusted mortality was higher in the off-pump group at 5 years (14.47% vs 13.45%; RR, 1.08; 95% CI 1.02 to 1.15) and 10 years (25.18% vs 23.57%; RR, 1.07; 95% CI, 1.03 to 1.12). Overall, the hazard ratio for off-pump vs on-pump was 1.06 (95% CI, 1.00 to 1.13; p = 0.04). Conclusions. Off-pump CABG may be associated with decreased long-term survival. Further studies are needed to identify the reasons behind this finding. (C) 2013 by The Society of Thoracic Surgeons C1 Michael E DeBakey VA Med Ctr, Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX USA. St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX USA. Univ Minnesota, Minneapolis Vet Affairs Med Ctr, Div Cardiothorac Surg, Minneapolis, MN USA. Univ Texas SW Med Ctr Dallas, Div Cardiothorac Surg, Dallas, TX 75390 USA. Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Houston, TX USA. Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77005 USA. EM fbakaeen@bcm.edu NR 29 TC 16 Z9 17 U1 0 U2 1 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 JUN PY 2013 VL 95 IS 6 BP 1952 EP 1960 DI 10.1016/j.athoracsur.2013.02.064 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 149QF UT WOS:000319335400027 PM 23647861 ER PT J AU Zartman, AL Hilsabeck, RC Guarnaccia, CA Houtz, A AF Zartman, Andrea L. Hilsabeck, Robin C. Guarnaccia, Charles A. Houtz, Andrew TI The Pillbox Test: An Ecological Measure of Executive Functioning and Estimate of Medication Management Abilities SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Assessment; Executive functions; Test construction ID COGNITIVE FUNCTION; OLDER-ADULTS; ALZHEIMERS-DISEASE; PERFORMANCE; IMPAIRMENT; DECLINE; PREDICTORS; MEMORY; SCHIZOPHRENIA; ASSOCIATION AB Studies indicate that executive functioning (EF) is a strong predictor of everyday function. However, assessment can be problematic as no single standardized instrument is known to measure all EF domains simultaneously. Thus, the Pillbox Test was developed as a new measure tapping four EF factors through the real-time assessment of medication management, a complex instrumental activity of daily living. The Pillbox Test showed good criterion-related validity and was effective in differentiating graduated levels of executive dysfunction between a mixed neurological group, medical control group, and healthy community control group. This test also showed good convergent validity as it correlated significantly in expected directions with established EF measures in all four of selected EF domains and the Direct Assessment of Functional Status. Finally, a receiver operator characteristic curve found a sensitivity of 75 and specificity of 87.5, suggesting that the Pillbox Test is a promising new ecological measure of EF. C1 [Zartman, Andrea L.; Guarnaccia, Charles A.] Univ N Texas, Dept Psychol, Denton, TX 76203 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Houtz, Andrew] Cognit Solut, Ft Worth, TX USA. RP Zartman, AL (reprint author), VA North Texas Hlth Care Syst, Mental Hlth 4500 S Lancaster Rd 116A, Dallas, TX 75216 USA. EM andrea.zartman@va.gov NR 64 TC 7 Z9 7 U1 4 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JUN PY 2013 VL 28 IS 4 BP 307 EP 319 DI 10.1093/arclin/act014 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA 148XI UT WOS:000319281500001 PM 23502807 ER PT J AU Thaler, NS Goldstein, G Pettegrew, JW Luther, JF Reynolds, CR Allen, DN AF Thaler, Nicholas S. Goldstein, Gerald Pettegrew, Jay W. Luther, James F. Reynolds, Cecil R. Allen, Daniel N. TI Developmental Aspects of Working and Associative Memory SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Learning and memory; Assessment ID SHORT-TERM-MEMORY; TEMPORAL-LOBE; BRIEF-HISTORY; LONG-TERM AB Developmental differences between working and long-term associative memory were evaluated through a cross-sectional age difference study based on data from a memory batterys standardization sample. The scores of 856 children and adolescents ranging from 5 to 17 years of age were compared on memory subtests that assess verbal working and long-term memory. Data were examined using curve fitting and ANOVA procedures that evaluated age group and years of age differences. The major finding was that the developmental trajectories across age differed substantially between the two memory domains. The working memory trajectory was linear until age 11, whereas the long-term memory trajectory was curvilinear with an inflection point at age 8. Both trajectories plateaued after age 11. ANOVAs produced significant interactions between tests of working and associative memory with age, supporting the view that the age trajectories had differing courses. The results are discussed in terms of neurobiological implications for the two memory systems studied. C1 [Thaler, Nicholas S.; Allen, Daniel N.] Univ Nevada, Las Vegas, NV 89154 USA. [Goldstein, Gerald; Luther, James F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Pettegrew, Jay W.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Reynolds, Cecil R.] Texas A&M Univ, College Stn, TX USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM ggold@nb.net FU Mental Illness Research, Education, and Clinical Center (MIRECC) VISN-IV, Pittsburgh, PA; Medical Research Service, Department of Veterans Affairs FX This research was supported by the Mental Illness Research, Education, and Clinical Center (MIRECC) VISN-IV, Pittsburgh, PA, and by the Medical Research Service, Department of Veterans Affairs. NR 28 TC 3 Z9 3 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JUN PY 2013 VL 28 IS 4 BP 348 EP 355 DI 10.1093/arclin/acs114 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 148XI UT WOS:000319281500004 PM 23341435 ER PT J AU Meadows, ME Chang, G Jones, JA Antin, JR Orav, EJ AF Meadows, Mary-Ellen Chang, Grace Jones, Jennifer A. Antin, Joseph R. Orav, E. John TI Predictors of Neuropsychological Change in Patients with Chronic Myelogenous Leukemia and Myelodysplastic Syndrome SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Cancer; Neuropsychology; Hematological malignancy; Cognition; Cancer treatment; Hematopoietic stem cell transplantation ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SELECTIVE REMINDING TEST; QUALITY-OF-LIFE; CANCER-PATIENTS; COGNITIVE FUNCTION; NORMATIVE DATA; ADULT SURVIVORS; VERBAL FLUENCY; CHEMOTHERAPY AB This study examined the course of neuropsychological functioning in patients with chronic myelogeous leukemia (n 91) or myelodysplastic syndrome (n 15) who underwent standard treatment for their disease or allogeneic hematopoietic stem cell transplantation (HSCT) at baseline, 12 months, and 18 months post-treatment. At baseline, 23 of the participants (n 75) in the longitudinal sample had Z-scores on at least one of the neuropsychological tests that were 1.4. Participants in the study showed improvement over baseline at the 12 and 18 months assessments. The average Z-scores for the six cognitive domains in the longitudinal data set over the course of the study ranged from 0.89 to 0.59. Significant predictors of change in neuropsychological test scores included age, with older participants showing less improvement over time. Other predictors included baseline cognitive domains (language, memory, and attention), previous cocaine use, disease status, intelligence quotient, and quality of life measures. Findings support previous studies in patients with hematological malignancies who showed cognitive impairments at baseline prior to HSCT. However, there was little evidence for further cognitive decline over the course of 18 months. C1 [Meadows, Mary-Ellen] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Meadows, Mary-Ellen; Chang, Grace; Jones, Jennifer A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Meadows, Mary-Ellen; Chang, Grace; Antin, Joseph R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Antin, Joseph R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Orav, E. John] Harvard Univ, Sch Med, Dept Med Biostat, Boston, MA USA. RP Meadows, ME (reprint author), Brigham & Womens Hosp, Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM mmeadows@partners.org FU American Cancer Society [RSG-01-246-01-PBP]; National Institute on Alcohol Abuse and Alcoholism [K24 AA 000289] FX This work was supported in part by the American Cancer Society (RSG-01-246-01-PBP to GC) and the National Institute on Alcohol Abuse and Alcoholism (K24 AA 000289 to GC). NR 56 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JUN PY 2013 VL 28 IS 4 BP 363 EP 374 DI 10.1093/arclin/acs141 PG 12 WC Psychology, Clinical; Psychology SC Psychology GA 148XI UT WOS:000319281500006 PM 23391504 ER PT J AU Goyal, RK Chaudhury, A AF Goyal, Raj K. Chaudhury, Arun TI Structure activity relationship of synaptic and junctional neurotransmission SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Review DE Postsynaptic potentials; Junction potentials; Smooth muscle neuromuscular transmission; Autonomic ganglia; Enteric nervous system; Nonsynaptic neurotransmission; Modes of neurotransmission ID ENTERIC NERVOUS-SYSTEM; GUINEA-PIG ILEUM; NICOTINIC ACETYLCHOLINE-RECEPTORS; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE SYNTHASE; DENSE-CORED VESICLES; PURINERGIC NEUROMUSCULAR-TRANSMISSION; ELECTRON MICROSCOPIC IDENTIFICATION; INHIBITORY POSTSYNAPTIC POTENTIALS; SYMPATHETIC PREGANGLIONIC NEURONS AB Chemical neurotransmission may include transmission to local or remote sites. Locally, contact between 'bare' portions of the bulbous nerve terminal termed a varicosity and the effector cell may be in the form of either synapse or non-synaptic contact. Traditionally, all local transmissions between nerves and effector cells are considered synaptic in nature. This is particularly true for communication between neurons. However, communication between nerves and other effectors such as smooth muscles has been described as nonsynaptic or junctional in nature. Nonsynaptic neurotransmission is now also increasingly recognized in the CNS. This review focuses on the relationship between structure and function that orchestrate synaptic and junctional neurotransmissions. A synapse is a specialized focal contact between the presynaptic active zone capable of ultrafast release of soluble transmitters and the postsynaptic density that cluster ionotropic receptors. The presynaptic and the postsynaptic areas are separated by the 'closed' synaptic cavity. The physiological hallmark of the synapse is ultrafast postsynaptic potentials lasting milliseconds. In contrast, junctions are juxtapositions of nerve terminals and the effector cells without clear synaptic specializations and the junctional space is 'open' to the extracellular space. Based on the nature of the transmitters, postjunctional receptors and their separation from the release sites, the junctions can be divided into 'close' and 'wide' junctions. Functionally, the 'close' and the 'wide' junctions can be distinguished by postjunctional potentials lasting similar to 1 s and tens of seconds, respectively. Both synaptic and junctional communications are common between neurons; however, junctional transmission is the rule at many neuro-non-neural effectors. Published by Elsevier B.V. C1 [Goyal, Raj K.] VA Boston Healthcare Syst, GI Div, Ctr Swallowing & Motil Disorders, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goyal, RK (reprint author), Harvard Univ, Sch Med, VA Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-062867] FX This work was supported by a National Institute of Diabetes and Digestive and Kidney Diseases grant (DK-062867). The authors wish to thank Antonietta D'Urso for help with preparation of manuscript. We also thank Dr. Joel Bornstein for his constructive criticisms. NR 231 TC 11 Z9 11 U1 2 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 EI 1872-7484 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD JUN PY 2013 VL 176 IS 1-2 BP 11 EP 31 DI 10.1016/j.autneu.2013.02.012 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 151UO UT WOS:000319485900004 PM 23535140 ER PT J AU Sylvia, L AF Sylvia, L. TI NEWTx Program for Bipolar Disorders SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE nutrition; exercise; bipolar disorder; cognitive behavioral therapy C1 [Sylvia, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 10 EP 10 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800007 ER PT J AU Thase, ME AF Thase, M. E. TI Clustering of depressive and manic symptoms in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar affective disorder; depression; hypomania; mania; mixed states C1 [Thase, M. E.] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 18 EP 18 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800029 ER PT J AU Reilly-Harrington, NA Sylvia, LG Leon, AC Shesler, LW Ketter, TA Bowden, CL Calabrese, JR Friedman, ES Ostacher, MJ Iosifescu, DV Rabideau, D Nierenberg, AA AF Reilly-Harrington, N. A. Sylvia, L. G. Leon, A. C. Shesler, L. W. Ketter, T. A. Bowden, C. L. Calabrese, J. R. Friedman, E. S. Ostacher, M. J. Iosifescu, D. V. Rabideau, D. Nierenberg, A. A. TI The medication recommendation tracking form: a novel tool for tracking changes in prescribed medication, clinical decision making, and use in comparative effectiveness research SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar; comparative effectiveness; training; assessment; methodology C1 [Reilly-Harrington, N. A.; Sylvia, L. G.; Leon, A. C.; Shesler, L. W.; Ketter, T. A.; Bowden, C. L.; Calabrese, J. R.; Friedman, E. S.; Ostacher, M. J.; Iosifescu, D. V.; Rabideau, D.; Nierenberg, A. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 20 EP 21 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800035 ER PT J AU Thase, ME AF Thase, M. E. TI Clinical perspective on RDoC and ROAMER utility SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar disorder; depression; dimensional assessment; RDOCs; ROAMER; cognitive dysfunction; insomnia C1 [Thase, M. E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Thase, M. E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 37 EP 37 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800079 ER PT J AU Iosifescu, DV Gilmer, W Fan, A Rappaport, M Deckersbach, T Nierenberg, AA AF Iosifescu, D. V. Gilmer, W. Fan, A. Rappaport, M. Deckersbach, T. Nierenberg, A. A. TI Memantine, a glutamate NMDA receptor antagonist, for cognitive deficits in euthymic bipolar subjects SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE memantine; glutamate NMDA receptor antagonist; cognition; attention; memory; social function C1 [Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY USA. [Gilmer, W.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Fan, A.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Rappaport, M.] Emory Univ, Sch Med, Atlanta, GA USA. [Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA. [Deckersbach, T.; Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 40 EP 40 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800084 ER PT J AU Biederman, J AF Biederman, J. TI Further evidence for robust familiality of pediatric bipolar-I disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE familiality meta-analysis C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 63 EP 64 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800139 ER PT J AU Stange, JP Sylvia, L Magalhaes, PVS Frank, E Otto, MW Miklowitz, DJ Berk, M Nierenberg, AA Deckersbach, T AF Stange, J. P. Sylvia, L. Magalhaes, P. V. S. Frank, E. Otto, M. W. Miklowitz, D. J. Berk, M. Nierenberg, A. A. Deckersbach, T. TI Extreme attributions predict transition from depression to mania in bipolar disorder: results from STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE attributional style; cognitive flexibility; course of illness; mania; depression C1 [Stange, J. P.] Temple Univ, Philadelphia, PA 19122 USA. [Sylvia, L.; Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Magalhaes, P. V. S.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil. [Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. [Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia. [Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 78 EP 78 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800174 ER PT J AU Eisner, L Gironde, S Deckersbach, T AF Eisner, L. Gironde, S. Deckersbach, T. TI Enhancing emotion regulation in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE mindfulness; emotion regulation; distress tolerance; group therapy C1 [Eisner, L.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA USA. [Eisner, L.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Res Program, Boston, MA USA. [Gironde, S.] McLean Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 97 EP 98 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800223 ER PT J AU Biederman, J Woodworth, K Martelon, M AF Biederman, J. Woodworth, K. Martelon, M. TI Personal and familial correlates of the child behavior checklist (CBCL)-severe dysregulation profile SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE mood disorders; severity of illness index; screening instrument C1 [Biederman, J.; Woodworth, K.; Martelon, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 112 EP 112 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800260 ER PT J AU Wozniak, J Hernandez, M AF Wozniak, J. Hernandez, M. TI High level of persistence of pediatric bipolar-1 disorder from childhood onto adolescent years: a four year prospective longitudinal follow-up study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar disorder; children; adolescent; course; follow-up C1 [Wozniak, J.; Hernandez, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 116 EP 116 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800269 ER PT J AU Fried, R Biederman, J Kenworthy, T Wozniak, J AF Fried, R. Biederman, J. Kenworthy, T. Wozniak, J. TI Distinguishing the executive functioning deficits of pediatric bipolar disorder from attention deficit hyperactivity disorder utilizing computerized assessment SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE neuropsychology; CANTAB; executive funcitning; bipolar youth C1 [Fried, R.; Biederman, J.; Kenworthy, T.; Wozniak, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 128 EP 128 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800298 ER PT J AU Ketter, TA Sachs, G Lu, K Laszlovszky, I Nagy, K Starace, A Durgam, S AF Ketter, T. A. Sachs, G. Lu, K. Laszlovszky, I. Nagy, K. Starace, A. Durgam, S. TI Long-term safety and tolerability of open-label cariprazine in patients with bipolar I disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE cariprazine; bipolar disorder; acute mania; clinical trial C1 [Ketter, T. A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Sachs, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lu, K.; Starace, A.; Durgam, S.] Forest Res Inst, Jersey City, NJ USA. [Laszlovszky, I.; Nagy, K.] Gedeon Richter Plc, Budapest, Hungary. NR 0 TC 0 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 134 EP 134 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800312 ER PT J AU Loebel, A Cucchiaro, J Silva, R Hsu, J Sarma, K Sachs, G Calabrese, JR AF Loebel, A. Cucchiaro, J. Silva, R. Hsu, J. Sarma, K. Sachs, G. Calabrese, J. R. TI Lurasidone adjunctive to lithium or valproate for the treatment of bipolar I depression: results of a 6-week, double-blind, placebo-controlled study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar disorder; depression; atypical antipsychotics; randomized clinical trial C1 [Loebel, A.; Cucchiaro, J.; Silva, R.; Hsu, J.; Sarma, K.] Sunovion Pharmaceut Inc, Ft Lee, NJ USA. [Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sachs, G.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 137 EP 138 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800322 ER PT J AU Loebel, A Cucchiaro, J Silva, R Sarma, K Kroger, H Calabrese, JR Sachs, G AF Loebel, A. Cucchiaro, J. Silva, R. Sarma, K. Kroger, H. Calabrese, J. R. Sachs, G. TI Lurasidone monotherapy for the treatment of bipolar I depression: results of a 6-week, double-blind, placebo-controlled study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar disorder; depression; atypical antipsychotics; randomized clinical trial C1 [Loebel, A.; Cucchiaro, J.; Silva, R.; Sarma, K.; Kroger, H.] Sunovion Pharmaceut Inc, Ft Lee, NJ USA. [Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sachs, G.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 138 EP 138 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800323 ER PT J AU Sachs, G Siu, C Cucchiaro, J Silva, R Grossman, F Hsu, J Kalali, A Loebel, A AF Sachs, G. Siu, C. Cucchiaro, J. Silva, R. Grossman, F. Hsu, J. Kalali, A. Loebel, A. TI Effect of personality traits on treatment outcomes in bipolar depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar depression; personality traits; treatment outcomes C1 [Sachs, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Siu, C.] Data Power Inc, Flemington, NJ USA. [Cucchiaro, J.; Silva, R.; Grossman, F.; Hsu, J.; Loebel, A.] Sunivion Pharmaceut Inc, Ft Lee, NJ USA. Quintiles, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 139 EP 139 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800325 ER PT J AU Deckersbach, T Peters, A Sylvia, L Urdahl, A Magalhaes, PVS Otto, MW Frank, E Miklowitz, DJ Berk, M Kinrys, G Nierenberg, AA AF Deckersbach, T. Peters, A. Sylvia, L. Urdahl, A. Magalhaes, P. V. S. Otto, M. W. Frank, E. Miklowitz, D. J. Berk, M. Kinrys, G. Nierenberg, A. A. TI The role of co-morbid anxiety in psychosocial treatment for acute bipolar depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE lamotrigine; adolescents; depression; bipolar C1 [Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA. [Deckersbach, T.; Sylvia, L.; Kinrys, G.; Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peters, A.] Univ Illinois, Chicago, IL USA. [Urdahl, A.] Childrens Hosp Wisconsin, Community Serv, Milwaukee, WI 53201 USA. [Magalhaes, P. V. S.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil. [Otto, M. W.] Boston Univ, Boston, MA 02215 USA. [Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. [Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 146 EP 146 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800343 ER PT J AU Sylvia, L Salcedo, S Peters, AT Magalhaes, PVS Frank, E Miklowitz, DJ Otto, MW Berk, M Bernstein, EE Nierenberg, AA Deckersbach, T AF Sylvia, L. Salcedo, S. Peters, A. T. Magalhaes, P. V. S. Frank, E. Miklowitz, D. J. Otto, M. W. Berk, M. Bernstein, E. E. Nierenberg, A. A. Deckersbach, T. TI Sleep disturbance moderates psychotherapy outcomes in patients with bipolar disorder: a STEP-BD report SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE sleep disturbance; insomnia; hypersomnia; psychotherapy; depressive episode C1 [Sylvia, L.; Salcedo, S.; Otto, M. W.; Bernstein, E. E.; Nierenberg, A. A.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peters, A. T.] Univ Illinois, Chicago, IL USA. [Magalhaes, P. V. S.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil. [Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. [Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia. [Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA. RI Magalhaes, Pedro/A-8519-2008 OI Magalhaes, Pedro/0000-0002-5644-6357 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 147 EP 147 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800345 ER PT J AU Sylvia, L Leon, A Nierenberg, AA Bowden, C Friedman, E Greiter, E Iosifescu, DV Thase, ME Ketter, TA Calabrese, JR Rabideau, D Ostacher, M Reilly-Harrington, NA AF Sylvia, L. Leon, A. Nierenberg, A. A. Bowden, C. Friedman, E. Greiter, E. Iosifescu, D. V. Thase, M. E. Ketter, T. A. Calabrese, J. R. Rabideau, D. Ostacher, M. Reilly-Harrington, N. A. TI Predictors and outcomes of quality of life and life functioning in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE bipolar disorder; life functioning; quality of life; lithium C1 [Sylvia, L.; Nierenberg, A. A.; Greiter, E.; Rabideau, D.; Reilly-Harrington, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leon, A.] Weill Cornell Med Coll, New York, NY USA. [Bowden, C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Friedman, E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY USA. [Thase, M. E.] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ketter, T. A.; Ostacher, M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Reilly-Harrington, N. A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 148 EP 148 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800348 ER PT J AU Kozhevnikov, M Kozhevnikov, M Yu, CJ Blazhenkova, O AF Kozhevnikov, Maria Kozhevnikov, Michael Yu, Chen Jiao Blazhenkova, Olesya TI Creativity, visualization abilities, and visual cognitive style SO BRITISH JOURNAL OF EDUCATIONAL PSYCHOLOGY LA English DT Article ID MENTAL-IMAGERY; SPATIAL VISUALIZATION; DOMAIN SPECIFICITY; OBJECT; METAANALYSIS; POTENTIALS; VALIDITY AB Background Despite the recent evidence for a multi-component nature of both visual imagery and creativity, there have been no systematic studies on how the different dimensions of creativity and imagery might interrelate. Aims The main goal of this study was to investigate the relationship between different dimensions of creativity (artistic and scientific) and dimensions of visualization abilities and styles (object and spatial). In addition, we compared the contributions of object and spatial visualization abilities versus corresponding styles to scientific and artistic dimensions of creativity. Samples Twenty-four undergraduate students (12 females) were recruited for the first study, and 75 additional participants (36 females) were recruited for an additional experiment. Method Participants were administered a number of object and spatial visualization abilities and style assessments as well as a number of artistic and scientific creativity tests. Results The results show that object visualization relates to artistic creativity and spatial visualization relates to scientific creativity, while both are distinct from verbal creativity. Furthermore, our findings demonstrate that style predicts corresponding dimension of creativity even after removing shared variance between style and visualization ability. The results suggest that styles might be a more ecologically valid construct in predicting real-life creative behaviour, such as performance in different professional domains. C1 [Kozhevnikov, Maria; Yu, Chen Jiao] Natl Univ Singapore, Dept Psychol, Singapore 117570, Singapore. [Kozhevnikov, Maria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kozhevnikov, Michael] Norfolk State Univ, Dept Engn, Norfolk, VA USA. [Blazhenkova, Olesya] Sabanci Univ, Fac Arts & Social Sci, Istanbul, Turkey. RP Kozhevnikov, M (reprint author), Natl Univ Singapore, Dept Psychol, Block AS4,Level 2,9 Arts Link, Singapore 117570, Singapore. EM mkozhevn@nmr.mgh.harvard.edu RI Blazhenkova, Olesya/H-8367-2016 OI Blazhenkova, Olesya/0000-0002-9513-7258 NR 52 TC 15 Z9 15 U1 3 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0998 EI 2044-8279 J9 BRIT J EDUC PSYCHOL JI Br. J. Educ. Psychol. PD JUN PY 2013 VL 83 IS 2 BP 196 EP 209 DI 10.1111/bjep.12013 PG 14 WC Psychology, Educational SC Psychology GA 148WC UT WOS:000319277900002 PM 23692530 ER PT J AU Galsky, MD Hendricks, R Svatek, R Bangs, R Hoffman-Censits, J Clement, J Dreicer, R Guancial, E Hahn, N Lerner, SP O'Donnell, PH Quale, DZ Siefker-Radtke, A Shipley, W Sonpavde, G Vaena, D Vinson, J Rosenberg, J AF Galsky, Matthew D. Hendricks, Ryan Svatek, Robert Bangs, Rick Hoffman-Censits, Jean Clement, Jessica Dreicer, Robert Guancial, Elizabeth Hahn, Noah Lerner, Seth P. O'Donnell, Peter H. Quale, Diane Zipursky Siefker-Radtke, Arlene Shipley, William Sonpavde, Guru Vaena, Daniel Vinson, Jacob Rosenberg, Jonathan TI Critical analysis of contemporary clinical research in muscle-invasive and metastatic urothelial cancer SO CANCER LA English DT Article DE bladder cancer; urothelial cancer; metastatic; clinical trials ID BLADDER-CANCER; NEOADJUVANT CHEMOTHERAPY; PHASE-III; METHOTREXATE; VINBLASTINE; CISPLATIN; CLINICALTRIALS.GOV; DOXORUBICIN; CARCINOMA; TRIAL AB BACKGROUND There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities. METHODS These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites. RESULTS Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients). CONCLUSIONS The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease. Cancer 2013;119:19941998. (c) 2013 American Cancer Society. C1 [Galsky, Matthew D.; Hendricks, Ryan] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Svatek, Robert] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bangs, Rick; Quale, Diane Zipursky] Bladder Canc Advocacy Network, Bethesda, MD USA. [Hoffman-Censits, Jean] Jefferson Kimmel Canc Ctr, Philadelphia, PA USA. [Clement, Jessica] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Dreicer, Robert] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Guancial, Elizabeth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hahn, Noah] Indiana Univ, IU Simon Canc Ctr, Indianapolis, IN 46204 USA. [Lerner, Seth P.] Baylor Coll Med, Houston, TX 77030 USA. [O'Donnell, Peter H.] Univ Chicago, Chicago, IL 60637 USA. [Siefker-Radtke, Arlene] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shipley, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sonpavde, Guru] Univ Alabama Birmingham, Birmingham, AL USA. [Vaena, Daniel] Univ Iowa, Iowa City, IA USA. [Vinson, Jacob; Rosenberg, Jonathan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Galsky, MD (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu NR 13 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2013 VL 119 IS 11 BP 1994 EP 1998 DI 10.1002/cncr.27973 PG 5 WC Oncology SC Oncology GA 148VU UT WOS:000319277000012 PM 23456777 ER PT J AU Cury, FL Hunt, D Roach, M Shipley, W Gore, E Hsu, IC Krisch, RE Seider, MJ Sandler, H Lawton, C AF Cury, Fabio L. Hunt, Daniel Roach, Mack, III Shipley, William Gore, Elizabeth Hsu, I-Chow Krisch, Robert E. Seider, Michael J. Sandler, Howard Lawton, Colleen TI Prostate-specific antigen response after short-term hormone therapy plus external-beam radiotherapy and outcome in patients treated on Radiation Therapy Oncology Group study 9413 SO CANCER LA English DT Article DE prostate cancer; radiation therapy; androgen-deprivation therapy; prostate-specific antigen; prediction of outcomes ID NEOADJUVANT ANDROGEN DEPRIVATION; CANCER-SPECIFIC MORTALITY; PHASE-III TRIAL; SUPPRESSION THERAPY; DOSE RADIOTHERAPY; PRETREATMENT PSA; FAILURE; VELOCITY; DISEASE; RISK AB BACKGROUND The objective of this study was to assess the impact of a prostate-specific antigen (PSA) complete response (PSA-CR), measured at the end of external-beam radiotherapy and short-term hormone therapy, on treatment outcomes. METHODS The phase 3 Radiation Therapy Oncology Group 9413 trial, as part of its original protocol, used the assessment of PSA-CR (ie, PSA 0.3 ng/mL) at the end of short-term HT as a secondary endpoint. Short-term HT consisted of futamide plus a lutenizing hormone-releasing hormone agonist for 4 months. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. Cumulative incidence was used to estimate biochemical failure, distant metastasis, and disease-specific survival. Univariate and multivariate analyses were performed to correlate PSA-CR after short-term hormone therapy with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone status. Phoenix consensus definition was used to define PSA failure. RESULTS For 1070 evaluable patients, the median PSA at the end of short-term hormone therapy was 0.2 ng/mL. In total, 744 patients (70%) had a PSA-CR. At a median follow-up of 7.2 years, failure to obtain a PSA-CR was associated significantly with worse disease-specific survival (P = .0003; hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.38-2.97), with worse disease-free survival (P = .003; HR, 1.28; 95% CI, 1.09-1.50), and with a higher incidence of distant metastasis (P = .0002; HR, 1.92; 95% CI, 1.37-2.69) and biochemical failure (P < .0001; HR, 1.57; 95% CI, 1.29-1.91). Other factors that were associated with worse disease-specific survival were Gleason scores from 8 to 10 (P = .0002; HR, 3.06; 95% CI, 1.71-5.47) and PSA levels >20 ng/mL (P = .04; HR, 1.55; 95% CI, 1.02-2.30). CONCLUSIONS The current results indicated that failure to obtain a PSA-CR (PSA 0.3 ng/mL) after short-term hormone therapy and external-beam radiotherapy appears to be an independent predictor of unfavorable outcomes and could help identify patients who may benefit from the addition of long-term androgen ablation. Cancer 2013;119:19992004. (c) 2013 American Cancer Society. C1 [Cury, Fabio L.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Hunt, Daniel] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Roach, Mack, III; Hsu, I-Chow] Univ Calif San Francisco, Dept Radiat Oncol, Helen Diller Comprehens Canc Ctr, San Francisco, CA USA. [Shipley, William] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gore, Elizabeth; Lawton, Colleen] Med Coll Wisconsin, Madison, WI USA. [Krisch, Robert E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Seider, Michael J.] Akron City Hosp, Akron, OH USA. [Sandler, Howard] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. RP Cury, FL (reprint author), 1650 Cedar Ave,D5-400, Montreal, PQ H3G 1A4, Canada. EM fabio.cury@muhc.mcgill.ca FU RTOG [U10 CA21661]; Community Clinical Oncology Program from the National Cancer Institute [U10 CA37422]; Pennsylvania Department of Health Formula Grant [4100050889] FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG) and was supported by RTOG grant U10 CA21661, Community Clinical Oncology Program grant U10 CA37422 from the National Cancer Institute, and the 2009 Pennsylvania Department of Health Formula Grant 4100050889. NR 23 TC 5 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2013 VL 119 IS 11 BP 1999 EP 2004 DI 10.1002/cncr.28019 PG 6 WC Oncology SC Oncology GA 148VU UT WOS:000319277000013 PM 23504930 ER PT J AU Zhu, JY Sharma, DB Chen, AB Johnson, BE Weeks, JC Schrag, D AF Zhu, Junya Sharma, Dhruv B. Chen, Aileen B. Johnson, Bruce E. Weeks, Jane C. Schrag, Deborah TI Comparative effectiveness of three platinum-doublet chemotherapy regimens in elderly patients with advanced nonsmall cell lung cancer SO CANCER LA English DT Article DE nonsmall cell lung cancer; survival; first-line chemotherapy; platinum-doublet; propensity score analysis; SEER-Medicare ID PHASE-III TRIAL; PACLITAXEL PLUS CARBOPLATIN; RANDOMIZED CONTROLLED-TRIALS; SEER-MEDICARE DATA; LEUKEMIA GROUP-B; PROPENSITY SCORE; COMORBIDITY INDEX; MULTICENTER TRIAL; CISPLATIN; COMBINATION AB BACKGROUND Randomized trials report equivalent efficacy among various combinations of platinum-based regimens in advanced nonsmall cell lung cancer (NSCLC). Their relative effectiveness and comparability based on squamous versus nonsquamous histology is uncertain. METHODS The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to identify first-line chemotherapy agents administered to Medicare beneficiaries with stage IIIB or IV NSCLC diagnosed from 2000 to 2007. Overall survival was compared between patients who received the 3 most common regimens: carboplatin-paclitaxel, carboplatin-gemcitabine, and carboplatin-docetaxel. Stratified analyses distinguished between the outcomes of patients with squamous versus nonsquamous cell histology. Multivariable Cox proportional hazards models and propensity score analyses facilitated adjustment for imbalance in measurable patient characteristics. RESULTS Of the 15,318 patients who received first-line chemotherapy, 43.1% received carboplatin-paclitaxel, 14.3% received carboplatin-gemcitabine, 8.5% received carboplatin-docetaxel, and 34.1% received other regimens. The median survival was 8.0 months (interquartile range [IQR], 3.5-17.4 months) for carboplatin-paclitaxel, 7.3 months (IQR, 3.4-15.2 months) for carboplatin-gemcitabine, and 7.5 months (IQR, 3.2-16.0 months) for carboplatin-docetaxel. Both multivariable and propensity score-adjusted Cox models demonstrated a slight inferiority associated with carboplatin-gemcitabine or carboplatin-docetaxel versus carboplatin-paclitaxel, with a hazard ratio of 1.10 (95% confidence interval, 1.04-1.15) and 1.09 (95% confidence interval, 1.02-1.16), respectively, in propensity score-stratified models. Among the subgroup of 2063 patients with squamous carcinoma, propensity score-stratified analyses had a higher risk of death (hazard ratio, 1.20; 95% confidence interval, 1.07-1.35) associated with carboplatin-gemcitabine versus carboplatin-paclitaxel. CONCLUSIONS Carboplatin-paclitaxel was associated with slightly better survival compared with carboplatin-gemcitabine or carboplatin-docetaxel within the Medicare population with advanced NSCLC, and this was most pronounced for patients who had squamous cell histology. Cancer 2013;119:20482060. (c) 2013 American Cancer Society. C1 [Zhu, Junya] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. [Sharma, Dhruv B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Chen, Aileen B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Johnson, Bruce E.; Weeks, Jane C.; Schrag, Deborah] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnson, Bruce E.; Weeks, Jane C.; Schrag, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Bruce E.; Weeks, Jane C.; Schrag, Deborah] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Internal Med, Boston, MA 02115 USA. RP Zhu, JY (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA. EM junya_zhu@dfci.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 FU Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program [HHSA290201000006I]; National Cancer Institute (NCI) [RC2CA148185-01]; NCI [PO1-CA134294]; Sanofi; Genentech; Astra Zeneca FX This project was funded under contract no. HHSA290201000006I (to Drs. Schrag and Schneeweiss) from the Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. Project support was also obtained from the National Cancer Institute (NCI) RC2CA148185-01 (to Dr. Weeks). Dr. Sharma was supported by NCI grant PO1-CA134294. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the AHRQ, the NCI, or the U.S. Department of Health and Human Services.; Dr. Johnson is a paid consultant to Sanofi, Genentech, and Astra Zeneca. NR 54 TC 10 Z9 10 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2013 VL 119 IS 11 BP 2048 EP 2060 DI 10.1002/cncr.28022 PG 13 WC Oncology SC Oncology GA 148VU UT WOS:000319277000019 PM 23564469 ER PT J AU Rhondali, W Perez-Cruz, P Hui, D Chisholm, GB Dalal, S Baile, W Chittenden, E Bruera, E AF Rhondali, Wadih Perez-Cruz, Pedro Hui, David Chisholm, Gary B. Dalal, Shalini Baile, Walter Chittenden, Eva Bruera, Eduardo TI Patientphysician communication about code status preferences A Randomized Controlled Trial SO CANCER LA English DT Article DE code status; advanced cancer; communication; patient preferences; randomized controlled trial ID NOT-RESUSCITATE ORDERS; BREAKING BAD-NEWS; SYMPTOM ASSESSMENT SCALE; LIFE DECISION-MAKING; INTENSIVE-CARE-UNIT; CANCER-PATIENTS; PATIENT PREFERENCES; PALLIATIVE CARE; CARDIOPULMONARY-RESUSCITATION; CLINICAL-TRIALS AB BACKGROUND Code status discussions are important in cancer care, but the best modality for such discussions has not been established. The objective of this study was to determine the impact of a physician ending a code status discussion with a question (autonomy approach) versus a recommendation (beneficence approach) on patients' do-not-resuscitate (DNR) preference. METHODS Patients in a supportive care clinic watched 2 videos showing a physicianpatient discussion regarding code status. Both videos were identical except for the ending: one ended with the physician asking for the patient's code status preference and the other with the physician recommending DNR. Patients were randomly assigned to watch the videos in different sequences. The main outcome was the proportion of patients choosing DNR for the video patient. RESULTS A total of 78 patients completed the study, and 74% chose DNR after the question video, whereas 73% chose DNR after the recommendation video. Median physician compassion score was very high and not different for both videos. All 30 of 30 patients who had chosen DNR for themselves and 30 of 48 patients who had not chosen DNR for themselves chose DNR for the video patient (100% versus 62%). Age (odds ratio=1.1/year) and white ethnicity (odds ratio=9.43) predicted DNR choice for the video patient. CONCLUSIONS Ending DNR discussions with a question or a recommendation did not impact DNR choice or perception of physician compassion. Therefore, both approaches are clinically appropriate. All patients who chose DNR for themselves and most patients who did not choose DNR for themselves chose DNR for the video patient. Age and race predicted DNR choice. Cancer 2013;119:20672073. (c) 2013 American Cancer Society. C1 [Rhondali, Wadih; Perez-Cruz, Pedro; Hui, David; Dalal, Shalini; Bruera, Eduardo] Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Houston, TX 77030 USA. [Rhondali, Wadih] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Dept Palliat Care, Lyon, France. [Perez-Cruz, Pedro] Pontificia Univ Catolica Chile, Fac Med, Dept Med Interna, Programa Med Paliat, Santiago, Chile. [Chisholm, Gary B.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Baile, Walter] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. [Chittenden, Eva] Massachusetts Gen Hosp, Dept Palliat Care, Boston, MA 02114 USA. RP Bruera, E (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Unit 1414, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ebruera@mdanderson.org RI Rhondali, Wadih/K-2348-2013 OI Rhondali, Wadih/0000-0001-7740-1476 FU National Institutes of Health [R01NR010162-01A1, R01CA1222292.01, R01CA12 4481-01]; University of Texas MD Anderson Cancer Center support grant [CA 016672] FX Dr. Bruera is supported in part by National Institutes of Health grants R01NR010162-01A1, R01CA1222292.01, and R01CA12 4481-01 and in part by the University of Texas MD Anderson Cancer Center support grant CA 016672. NR 46 TC 11 Z9 11 U1 3 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2013 VL 119 IS 11 BP 2067 EP 2073 DI 10.1002/cncr.27981 PG 7 WC Oncology SC Oncology GA 148VU UT WOS:000319277000021 PM 23564395 ER PT J AU Kang, JX Liu, A AF Kang, Jing X. Liu, Angela TI The role of the tissue omega-6/omega-3 fatty acid ratio in regulating tumor angiogenesis SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Omega-3 fatty acids; Omega-6 fatty acids; Fatty acid ratio; Angiogenesis; Cancer; Inflammation ID FAT-1 TRANSGENIC MICE; ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER; ARACHIDONIC-ACID; LIPID MEDIATORS; CELL MIGRATION; BREAST-CANCER; IN-VIVO; VEGF-C; ELEVATED OMEGA-3-FATTY-ACIDS AB Angiogenesis is a necessary step in tumor growth and metastasis. It is well established that the metabolites of omega-6 and omega-3 fatty acids, which must be obtained through the diet and cannot be synthesized de novo in mammals, have differential effects on cellular processes. Omega-6 fatty acid (n-6 FA)-derived metabolites promote angiogenesis by increasing growth factor expression whereas omega-3 fatty acids (n-3 FA) have anti-angiogenic and antitumor properties. However, most studies thus far have failed to account for the role of the n-6 FA/n-3 FA ratio in angiogenesis and instead examined the absolute levels of n-6 and n-3 FA. This review highlights the biochemical interactions between n-6 and n-3 FA and focuses on how the n-6/n-3 FA ratio in tissues modulates tumor angiogenesis. We suggest that future work should consider the n-6/n-3 FA ratio to be a key element in experimental design and analysis. Furthermore, we recommend that clinical interventions should aim to both reduce n-6 metabolites and simultaneously increase n-3 FA intake. C1 [Kang, Jing X.; Liu, Angela] Harvard Univ, Sch Med, Boston, MA USA. [Kang, Jing X.; Liu, Angela] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Charlestown, MA 02129 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149-13th St,Room 4001, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 97 TC 19 Z9 21 U1 2 U2 45 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 EI 1573-7233 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2013 VL 32 IS 1-2 SI SI BP 201 EP 210 DI 10.1007/s10555-012-9401-9 PG 10 WC Oncology SC Oncology GA 147DQ UT WOS:000319146200015 PM 23090260 ER PT J AU Peisley, A Hur, S AF Peisley, Alys Hur, Sun TI Multi-level regulation of cellular recognition of viral dsRNA SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Antiviral innate immunity; Double-stranded RNA; PKR; OAS; ADAR; TLR3; RIG-I; MDA5 ID DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTOR-3; PROTEIN-KINASE PKR; 2'-5' OLIGOADENYLATE SYNTHETASE; ANTIVIRAL INNATE IMMUNITY; HEPATITIS-DELTA VIRUS; INDUCIBLE GENE-I; RIG-I; BINDING DOMAIN; MESSENGER-RNA AB Effective antiviral immunity depends on accurate recognition of viral RNAs by the innate immune system. Double-stranded RNA (dsRNA) often accumulates in virally infected cells and was initially considered a unique viral signature that was sufficient to initiate antiviral response through dsRNA receptors and dsRNA-dependent effectors such as Toll-like receptor 3, retinoic acid inducible gene-1, protein kinase RNA-activated and oligoadenylate synthetase. However, dsRNA is also present in many cellular RNAs, raising a question of how these receptors and effectors discriminate between viral and cellular dsRNAs. Accumulating evidence suggests that innate immune sensors detect not only dsRNA structure but also other and often multiple features of RNA such as length, sequence, cellular location, post-transcriptional processing and modification, which are divergent between viral and cellular RNAs. This review summarizes recent findings on the substrate specificities of a few selected dsRNA-dependent effectors and receptors, which have revealed more complex mechanisms involved in cellular discrimination between self and non-self RNA. C1 [Peisley, Alys; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Peisley, Alys; Hur, Sun] Childrens Hosp, Program Cellular & Mol Med, Ctr Life Sci Boston, Boston, MA 02115 USA. RP Hur, S (reprint author), Childrens Hosp, Program Cellular & Mol Med, Ctr Life Sci Boston, 3 Blackfan Circle, Boston, MA 02115 USA. EM hur@idi.harvard.edu NR 158 TC 9 Z9 9 U1 0 U2 17 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUN PY 2013 VL 70 IS 11 BP 1949 EP 1963 DI 10.1007/s00018-012-1149-4 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148CK UT WOS:000319220100006 PM 22960755 ER PT J AU Valente, AJ Yoshida, T Izadpanah, R Delafontaine, P Siebenlist, U Chandrasekar, B AF Valente, Anthony J. Yoshida, Tadashi Izadpanah, Reza Delafontaine, Patrice Siebenlist, Ulrich Chandrasekar, Bysani TI Interleukin-18 enhances IL-18R/Noxl binding, and mediates TRAF3IP2-dependent smooth muscle cell migration. Inhibition by simvastatin SO CELLULAR SIGNALLING LA English DT Article DE Interleukin-18; TRAF3IP2; Nox1; Oxidative stress; SMC migration; Vascular diseases ID KAPPA-B KINASE; NADPH OXIDASE; CIKS ACT1; EXPRESSION; NOX1; ACTIVATION; STATINS; PROTEIN; ATHEROSCLEROSIS; PROLIFERATION AB We investigated the role of TRAF3 interacting protein 2 (TRAF3IP2), a redox-sensitive adapter protein and an upstream regulator of IKK and JNK in interleukin (IL)-18 induced smooth muscle cell migration, and the mechanism of its inhibition by simvastatin. The pleiotropic cytokine IL-18 induced human coronary artery SMC migration through the induction of TRAF3IP2. IL-18 induced Nox1-dependent ROS generation, TRAF3IP2 expression, and IKK/NF-kappa B and JNK/AP-1 activation. IL-18 induced its own expression and that of its receptor subunit IL-18R alpha. Using co-IP/IB and GST pull-down assays, we show for the first time that the subunits of the IL-18R heterodimer physically associate with Nox1 under basal conditions, and IL-18 appears to enhance their binding. Importantly, the HMG-coA reductase inhibitor simvastatin attenuated IL-18-induced TRAF3IP2 induction. These inhibitory effects were reversed by mevalonate and geranylgeranylpyrophosphate (GGPP), but not by famesylpyrophosphate (FPP). Interestingly, simvastatin, GGPP, FPP, or Rac1 inhibition did not modulate ectopically expressed TRAF3IP2. These results demonstrate that the promigratory effects of IL-18 are mediated through TRAF3IP2 in a redox-sensitive manner, and this may involve IL-18R/Nox1 physical association. Further, Simvastatin inhibits inducible, but not ectopically-xpressed TRAF3IP2. Targeting TRAF3IP2 may blunt progression of hyperplastic vascular diseases in vivo. (C) 2013 Elsevier Inc. All rights reserved. C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Yoshida, Tadashi; Izadpanah, Reza; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu FU Department of Veterans Affairs Research Career Scientist award; VA Office of Research and Development Biomedical Laboratory Research and Development Service Award [1I01BX000246]; NIH/NHLBI [HL-86787]; NHLBI [HL-70241, HL-80682] FX BC is a recipient of the Department of Veterans Affairs Research Career Scientist award, and is supported by VA Office of Research and Development Biomedical Laboratory Research and Development Service Award 1I01BX000246 and the NIH/NHLBI grant HL-86787. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government. PD is supported by NHLBI grants HL-70241 and HL-80682. The authors gratefully acknowledge the excellent technical assistance of Maria Gamez. NR 27 TC 8 Z9 9 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2013 VL 25 IS 6 BP 1447 EP 1456 DI 10.1016/j.cellsig.2013.03.007 PG 10 WC Cell Biology SC Cell Biology GA 147OD UT WOS:000319176000013 PM 23541442 ER PT J AU Leung, DT Uddin, T Xu, P Aktar, A Johnson, RA Rahman, MA Alam, MM Bufano, MK Eckhoff, G Wu-Freeman, Y Yu, YN Sultana, T Khanam, F Saha, A Chowdhury, F Khan, AI Charles, RC LaRocque, RC Harris, JB Calderwood, SB Kovac, P Qadri, F Ryan, ET AF Leung, Daniel T. Uddin, Taher Xu, Peng Aktar, Amena Johnson, Russell A. Rahman, Mohammad Arif Alam, Mohammad Murshid Bufano, Meagan Kelly Eckhoff, Grace Wu-Freeman, Ying Yu, Yanan Sultana, Tania Khanam, Farhana Saha, Amit Chowdhury, Fahima Khan, Ashraf I. Charles, Richelle C. LaRocque, Regina C. Harris, Jason B. Calderwood, Stephen B. Kovac, Pavol Qadri, Firdausi Ryan, Edward T. TI Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MEMORY B-CELL; INFLUENZAE TYPE-B; CONJUGATE VACCINE; PNEUMOCOCCAL POLYSACCHARIDES; CAPSULAR POLYSACCHARIDE; HOUSEHOLD CONTACTS; ANTIBODY-RESPONSES; ESCHERICHIA-COLI; HEALTHY-CHILDREN; IMMUNOGENICITY AB Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group. C1 [Leung, Daniel T.; Uddin, Taher; Aktar, Amena; Johnson, Russell A.; Rahman, Mohammad Arif; Alam, Mohammad Murshid; Sultana, Tania; Khanam, Farhana; Saha, Amit; Chowdhury, Fahima; Khan, Ashraf I.; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Leung, Daniel T.; Bufano, Meagan Kelly; Wu-Freeman, Ying; Yu, Yanan; Sultana, Tania; Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Eckhoff, Grace; Charles, Richelle C.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 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), ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh. EM dleung@partners.org RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012; OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801 FU ICDDR; Intramural Research Program of the National Institutes of Health; NIDDK; National Institutes of Health; National Institute of Allergy & Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, K08 AI089721, K08AI100923]; Fogarty International Center, Training Grant in Vaccine Development and Public Health [TW005572]; Career Development Award [K01 TW07409, TW07144]; Fogarty International Clinical Research Scholars award [R24 TW007988]; Swedish International Development Cooperation Agency; Physician Scientist Early Career Award from the Howard Hughes Medical Institute; Thrasher Research Fund Early Career Award; American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund FX This work was supported by the ICDDR, B and its donors, which provide unrestricted support to ICDDR, B 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 Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (U01 AI058935 [to S.B.C. and E.T.R.], R03 AI063079 [to F.Q.], U01 AI077883 [to E.T.R.], K08 AI089721 [to R.C.C.], and K08AI100923 [to D.T.L.]) and the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [to T.U., M.M.A., F.K., and F.Q.]), a Career Development Award (K01 TW07409 [to J.B.H.] and TW07144 [to R.C.L.]), and a Fogarty International Clinical Research Scholars award (R24 TW007988 [to R.A.J. and T.U.]), as well as by the Swedish International Development Cooperation Agency (to F.Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R.C.L.), a Thrasher Research Fund Early Career Award (to D.T.L.), and a postdoctoral fellowship in tropical infectious diseases from the American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund (to D.T.L.). NR 53 TC 9 Z9 9 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2013 VL 20 IS 6 BP 780 EP 788 DI 10.1128/CVI.00035-13 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151HO UT WOS:000319451500002 PM 23515016 ER PT J AU Diaz, PI Hong, BY Frias-Lopez, J Dupuy, AK Angeloni, M Abusleme, L Terzi, E Ioannidou, E Strausbaugh, LD Dongari-Bagtzoglou, A AF Diaz, Patricia I. Hong, Bo-Young Frias-Lopez, Jorge Dupuy, Amanda K. Angeloni, Mark Abusleme, Loreto Terzi, Evimaria Ioannidou, Effie Strausbaugh, Linda D. Dongari-Bagtzoglou, Anna TI Transplantation-Associated Long-Term Immunosuppression Promotes Oral Colonization by Potentially Opportunistic Pathogens without Impacting Other Members of the Salivary Bacteriome SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ORGAN-TRANSPLANTATION; INFECTION; MICROBIOME; RECIPIENTS; PERIODONTITIS; COMMUNITIES; MICROFLORA; FLORA AB Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome. C1 [Diaz, Patricia I.; Hong, Bo-Young; Angeloni, Mark; Abusleme, Loreto; Ioannidou, Effie; Dongari-Bagtzoglou, Anna] Univ Connecticut, Ctr Hlth, Dept Oral Hlth & Diagnost Sci, Div Periodontol, Farmington, CT USA. [Frias-Lopez, Jorge] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Dupuy, Amanda K.; Strausbaugh, Linda D.] Univ Connecticut, Ctr Appl Genet & Technol, Storrs, CT USA. [Abusleme, Loreto] Univ Chile, Fac Dent, Lab Oral Microbiol, Santiago, Chile. [Terzi, Evimaria] Boston Univ, Dept Comp Sci, Boston, MA 02215 USA. RP Diaz, PI (reprint author), Univ Connecticut, Ctr Hlth, Dept Oral Hlth & Diagnost Sci, Div Periodontol, Farmington, CT USA. EM pdiaz@uchc.edu; adongari@uchc.edu FU National Institutes of Health (NIH) [R21DE016466, R01DE021578] FX This study was supported by grants R21DE016466 and R01DE021578 from the National Institutes of Health (NIH). NR 43 TC 16 Z9 16 U1 1 U2 24 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2013 VL 20 IS 6 BP 920 EP 930 DI 10.1128/CVI.00734-12 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151HO UT WOS:000319451500020 PM 23616410 ER PT J AU Kocsis, B Brown, RE McCarley, RW Hajos, M AF Kocsis, Bernat Brown, Ritchie E. McCarley, Robert W. Hajos, Mihaly TI Impact of Ketamine on Neuronal Network Dynamics: Translational Modeling of Schizophrenia-Relevant Deficits SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Gamma oscillation; Mismatch negativity; N-methyl-d-aspartate receptors receptors; P300; Theta rhythm ID NMDA RECEPTOR HYPOFUNCTION; PARVALBUMIN-CONTAINING INTERNEURONS; MEDIAL PREFRONTAL CORTEX; HIPPOCAMPAL THETA-RHYTHM; STEADY-STATE RESPONSES; RAT VISUAL-CORTEX; LOW-DOSE KETAMINE; GAMMA-OSCILLATIONS; MISMATCH NEGATIVITY; WORKING-MEMORY AB Subanesthetic doses of the psychomimetic, ketamine, have been used for many years to elicit behavioral effects reminiscent of schizophrenia in both healthy humans and in animal models of the disease. More recently, there has been a move toward the use of simple neurophysiological measures (event-related potentials, brain oscillations) to assay the functional integrity of neuronal circuits in schizophrenia as these measures can be assessed in patients, healthy controls, intact animals, and even in brain slices. Furthermore, alterations of these measures are correlated with basic information processing deficits that are now considered central to the disease. Thus, here we review recent studies that determine the effect of ketamine on these measures and discuss to what extent they recapitulate findings in patients with schizophrenia. In particular, we examine methodological differences between human and animal studies and compare in vivo and in vitro effects of ketamine. Ketamine acts on multiple cortical and subcortical sites, as well as on receptors other than the N-methyl-d-aspartate receptor. Acute ketamine models' changes correlated with psychotic states (e.g. increased baseline gamma-band oscillations), whereas chronic ketamine causes cortical circuit changes and neurophysiological deficits (e.g. impaired event-related gamma-band oscillations) correlated with cognitive impairments in schizophrenia. C1 [Kocsis, Bernat] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Lab Neurophysiol,Dept Psychiat, Boston, MA 02215 USA. [Brown, Ritchie E.; McCarley, Robert W.] VA Boston Healthcare Syst, Dept Psychiat, Lab Neurosci, Brockton, MA USA. [Brown, Ritchie E.; McCarley, Robert W.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Hajos, Mihaly] Yale Univ, Sch Med, Comparat Med Sect, Brady Mem Lab, New Haven, CT 06510 USA. RP Kocsis, B (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Lab Neurophysiol,Dept Psychiat, 330 Brookline Ave,CLS 710, Boston, MA 02215 USA. EM bernat_kocsis@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132 FU Department of Veterans Affairs Medical Research Service Award; National Institute of Health [MH087777, HL095491, MH039683, MH094803] FX This work was supported by a Department of Veterans Affairs Medical Research Service Award (to RWM) and grants from the National Institute of Health: MH087777 (BK), HL095491 (BK and RWM), MH039683 (RWM), MH094803 (REB). NR 209 TC 33 Z9 33 U1 2 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD JUN PY 2013 VL 19 IS 6 SI SI BP 437 EP 447 DI 10.1111/cns.12081 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 149US UT WOS:000319347500009 PM 23611295 ER PT J AU Finnerty, CC Jeschke, MG Qian, WJ Kaushal, A Xiao, WZ Liu, T Gritsenko, MA Moore, RJ Camp, DG Moldawer, LL Elson, C Schoenfeld, D Gamelli, R Gibran, N Klein, M Arnoldo, B Remick, D Smith, RD Davis, R Tompkins, RG Herndon, DN AF Finnerty, Celeste C. Jeschke, Marc G. Qian, Wei-Jun Kaushal, Amit Xiao, Wenzhong Liu, Tao Gritsenko, Marina A. Moore, Ronald J. Camp, David G., II Moldawer, Lyle L. Elson, Constance Schoenfeld, David Gamelli, Richard Gibran, Nicole Klein, Matthew Arnoldo, Brett Remick, Daniel Smith, Richard D. Davis, Ronald Tompkins, Ronald G. Herndon, David N. CA Investigators Inflammation & Host TI Determination of Burn Patient Outcome by Large-Scale Quantitative Discovery Proteomics SO CRITICAL CARE MEDICINE LA English DT Article DE biomarker; burn; inflammation; liquid chromatography-mass spectrometry; plasma proteins; proteomic profiling ID ACTIVATED PROTEIN-C; MASS-SPECTROMETRY; INSULIN THERAPY; SEVERE SEPSIS; INJURY; INFLAMMATION; MANAGEMENT; SUPPORT; TRAUMA; TIME AB Objectives: Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry and multiplex cytokine analysis to profile the plasma proteome of survivors and nonsurvivors of massive burn injury to determine the proteomic survival signature following a major burn injury. Design: Proteomic discovery study. Setting: Five burn hospitals across the United States. Patients: Thirty-two burn patients (16 nonsurvivors and 16 survivors), 19-89 years old, were admitted within 96 hours of injury to the participating hospitals with burns covering more than 20% of the total body surface area and required at least one surgical intervention. Interventions: None. Measurements and Main Results: We found differences in circulating levels of 43 proteins involved in the acute-phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. Interleukin-4, interleukin-8, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, and beta 2-microglobulin correlated well with survival and may serve as clinical biomarkers. Conclusions: These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale liquid chromatography-mass spectrometry-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma, or critical illness. (Crit Care Med 2013; 41: 1421-1434) C1 [Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Finnerty, Celeste C.; Herndon, David N.] Shriners Hosp Children, Galveston, TX 77550 USA. [Finnerty, Celeste C.] Univ Texas Med Branch, Sealy Ctr Mol Med, Inst Translat Sci, Galveston, TX 77555 USA. [Jeschke, Marc G.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, Toronto, ON, Canada. [Jeschke, Marc G.] Univ Toronto, Div Plast Surg, Toronto, ON, Canada. [Qian, Wei-Jun; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Qian, Wei-Jun; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [Kaushal, Amit; Xiao, Wenzhong; Davis, Ronald] Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Stanford, CA 94305 USA. [Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA. [Elson, Constance; Schoenfeld, David; Tompkins, Ronald G.] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. [Elson, Constance; Schoenfeld, David; Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. [Gamelli, Richard] Loyola Univ, Stritch Sch Med, Dept Surg, Maywood, IL 60153 USA. [Gibran, Nicole; Klein, Matthew] Univ Washington, Harborview Med Ctr, Sch Med, Dept Surg, Seattle, WA 98104 USA. [Arnoldo, Brett] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Remick, Daniel] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Finnerty, CC (reprint author), Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. EM ccfinner@utmb.edu RI Smith, Richard/J-3664-2012; OI Smith, Richard/0000-0002-2381-2349; Remick, Daniel/0000-0002-2615-3713 FU National Institute of General Medical Sciences [U54 GM-62119-04, P50 GM-60338, R01 GM-56687, T32 GM-008256, 8 P41 GM103493-10]; National Institutes of Health National Center for Research Resources [RR018522, 5P41RR018522-10]; NIH [KL2RR029875, UL1RR029876]; U.S. Department of Energy [DE-AC05-76RL01830] FX Supported, in part, by a Large Scale Collaborative Research Grant from the National Institute of General Medical Sciences (U54 GM-62119-04) awarded to Dr. Tompkins at the Massachusetts General Hospital, Boston, MA and in part, by research grants awarded to Dr. Herndon at the University of Texas Medical Branch, Galveston, TX, by the National Institute of General Medical Sciences (P50 GM-60338, R01 GM-56687, T32 GM-008256). Portions of the research were supported by a grant from the National Institutes of Health National Center for Research Resources (RR018522 and 5P41RR018522-10) and National Institute of General Medical Sciences (8 P41 GM103493-10). Dr. Finnerty is an ITS Career Development Scholar supported, in part, by NIH KL2RR029875 and NIH UL1RR029876. LC-MS proteomic analyses were performed in the Environmental Molecular Sciences Laboratory, a U.S. Department of Energy national scientific user facility located at the Pacific Northwest National Laboratory in Richland, WA. The Pacific Northwest National Laboratory is a multiprogram national laboratory operated by Battelle Memorial Institute for the U.S. Department of Energy under Contract DE-AC05-76RL01830. NR 27 TC 19 Z9 20 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2013 VL 41 IS 6 BP 1421 EP 1434 DI 10.1097/CCM.0b013e31827c072e PG 14 WC Critical Care Medicine SC General & Internal Medicine GA 148TC UT WOS:000319269400024 PM 23507713 ER PT J AU Akgun, KM Tate, JP Pisani, M Fried, T Butt, AA Gibert, CL Huang, L Rodriguez-Barradas, MC Rimland, D Justice, AC Crothers, K AF Akguen, Kathleen M. Tate, Janet P. Pisani, Margaret Fried, Terri Butt, Adeel A. Gibert, Cynthia L. Huang, Laurence Rodriguez-Barradas, Maria C. Rimland, David Justice, Amy C. Crothers, Kristina TI Medical ICU Admission Diagnoses and Outcomes in Human Immunodeficiency Virus-Infected and Virus-Uninfected Veterans in the Combination Antiretroviral Era SO CRITICAL CARE MEDICINE LA English DT Article DE 30-day mortality; comorbidity; human immunodeficiency virus; medical ICU; Veterans Aging Cohort Study Index ID INTENSIVE-CARE-UNIT; HIV-NEGATIVE VETERANS; CIGARETTE-SMOKING; THERAPY ERA; HEPATITIS-C; MORTALITY; SURVIVAL; IMPACT; COHORT; RISK AB Objectives: Human immunodeficiency virus (HIV)-infected (HIV+) patients on combination antiretroviral therapy are living longer but have increased risk for aging-associated disease which may lead to increasing critical care requirements. We compare medical ICU admission characteristics and outcomes among HIV infected and demographically similar uninfected patients (uninfected) and considered whether an index which combines routine clinical biomarkers (the Veterans Aging Cohort Study Index) predicts 30-day medical ICU mortality. Design: Observational data analyses (Veterans Aging Cohort Study). Setting: Eight Veterans Affairs medical centers nationwide. Patients: HIV infected and uninfected with a medical ICU admission between 2002 and 2010. Intervention: None. Measurements and Main Results: Medical ICU admission was determined using bedsection (Veterans Affairs) and revenue center codes (Medicare). For Veterans Affairs admissions, we used clinical data to calculate Veterans Aging Cohort Study Index scores and multivariable logistic regression to determine factors associated with 30-day mortality. Overall, 539 of 3,620 (15%) HIV infected and 375 of 3,639 (10%) uninfected had a medical ICU admission; 72% and 78%, respectively, were Veterans Affairs based. HIV+ patients were younger at admission (p < 0.0001). Although most HIV+ patients were on antiretroviral therapy (71%) with undetectable HIV-1 RNA (54%), compared with uninfected they were more commonly admitted with respiratory diagnoses or infections (21% vs. 12%), were more likely to require mechanical ventilation (17% vs. 9%; p = 0.001), and had a higher mortality rate (18.6% vs. 11.2%, p = 0.003). Cardiovascular diagnoses were less common among HIV infected (18% vs. 29%; p < 0.0001). In logistic regression (c-statistic 0.87), a 5-point increment in Veterans Aging Cohort Study Index was associated with an odds ratio of death of 1.22 (95% confidence interval 1.14-1.30) among HIV infected and of 1.50 (95% confidence interval 1.29-1.76) among uninfected; infection/sepsis and respiratory diagnoses were also associated with mortality. Conclusions: Medical ICU admission was frequent, 30-day mortality higher, and mechanical ventilation more common in HIV infected compared with uninfected. The Veterans Aging Cohort Study Index calculated at medical ICU admission predicted 30-day mortality for HIV infected and uninfected. As more individuals age with HIV, their requirements for medical ICU care may be greater than demographically similar uninfected individuals. C1 [Akguen, Kathleen M.; Tate, Janet P.; Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA. [Akguen, Kathleen M.; Tate, Janet P.; Pisani, Margaret; Fried, Terri; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Fried, Terri] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Gibert, Cynthia L.] VAMC, Dept Med, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Washington, DC USA. [Huang, Laurence] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E De Bakey VAMC, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Rimland, David] Atlanta VA, Dept Med, Decatur, GA USA. [Rimland, David] Emory Univ, Decatur, GA USA. [Crothers, Kristina] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Akgun, KM (reprint author), VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA. EM kathleen.akgun@yale.edu RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Crothers, Kristina/0000-0001-9702-0371 FU Association of Subspecialty Physicians and CHEST Foundation of the American College of Chest Physicians T. Franklin Williams Award; National Institutes of Health, National Heart, Lung, and Blood Institute [K24 HL087713, R01 HL090342]; National Institute on Alcohol Abuse and Alcoholism [5U01AA013566-05]; National Institutes of Health; ASP-ACCP; Merck; ATS FX Supported, in part, by Association of Subspecialty Physicians and CHEST Foundation of the American College of Chest Physicians T. Franklin Williams Award (KMA); National Institutes of Health, National Heart, Lung, and Blood Institute K24 HL087713 (LH); National Institute on Alcohol Abuse and Alcoholism 5U01AA013566-05 (AJ); and National Institutes of Health, National Heart, Lung, and Blood Institute R01 HL090342 (KC).; Drs. Akgun, Tate, Gibert, Huang, Rodriguez-Barradas, Rimland, Justice, and Crothers received grant support from the National Institutes of Health. Dr. Akgun received grant support from ASP-ACCP (T Franklin Williams Award). Dr. Butt received grant support from Merck. Dr. Rodriguez-Barradas received support for travel from NIH. Dr. Butt lectured for Gilead. Dr. Crothers received educational presentation funding from ATS. NR 48 TC 26 Z9 27 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2013 VL 41 IS 6 BP 1458 EP 1467 DI 10.1097/CCM.0b013e31827caa46 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 148TC UT WOS:000319269400028 PM 23507717 ER PT J AU Clark, BJ Williams, A Feemster, LMC Bradley, KA Macht, M Moss, M Burnham, EL AF Clark, Brendan J. Williams, Andre Feemster, Laura M. Cecere Bradley, Katharine A. Macht, Madison Moss, Marc Burnham, Ellen L. CA NHLBI ARDS Network Investigators TI Alcohol Screening Scores and 90-Day Outcomes in Patients With Acute Lung Injury SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; alcohol misuse; alcohol use disorder; alcohol use disorders identification test; unhealthy alcohol use ID RESPIRATORY-DISTRESS-SYNDROME; DISORDERS IDENTIFICATION TEST; MECHANICALLY VENTILATED PATIENTS; CRITICALLY-ILL PATIENTS; RISK-FACTORS; TEST AUDIT; EPITHELIAL PERMEABILITY; HOSPITAL MORTALITY; CIGARETTE-SMOKING; CLINICAL-TRIAL AB Objectives: The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test that correspond to past-year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with acute lung injury. Design: Secondary analysis. Setting: The Acute Respiratory Distress Syndrome Network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multicenter clinical trials in patients with acute lung injury. Subjects: Patients meeting consensus criteria for acute lung injury enrolled in one of three recent Acute Respiratory Distress Syndrome Network clinical trials. Interventions: None. Measurements and Main Results: Of 1,133 patients enrolled in one of three Acute Respiratory Distress Syndrome Network studies, 1,037 patients had an Alcohol Use Disorders Identification Test score available for analysis. Alcohol misuse was common with 70 (7%) of patients having Alcohol Use Disorders Identification Test scores in zone 3 and 129 (12%) patients in zone 4. There was a U-shaped association between validated Alcohol Use Disorders Identification Test zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients having Alcohol Use Disorders Identification Test zone 4 compared with those in zone 2 (adjusted odds ratio 1.70; 95% confidence interval 1.00, 2.87; p = 0.048). Conclusions: Severe but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in acute lung injury patients. C1 [Clark, Brendan J.; Macht, Madison; Moss, Marc; Burnham, Ellen L.] Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Williams, Andre] Natl Jewish Hlth, Dept Biostat & Bioinformat, Denver, CO USA. [Feemster, Laura M. Cecere] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Feemster, Laura M. Cecere] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Clark, BJ (reprint author), Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA. EM brendan.clark@ucdenver.edu FU National Institutes of Health [K24-HL-089223, R24-AA-019661-01A1, N01 HR56167]; VA HSRD fellowship [TPM 61-037]; National Heart and Lung Bloos Institute; VA HSRD Fellowship FX Supported, in part, by National Institutes of Health (K24-HL-089223, R24-AA-019661-01A1) and National Institutes of Health contract N01 HR56167; VA HSR&D fellowship (TPM 61-037) to Dr. Cecere.; Dr. Clark received grant support from the National Heart and Lung Bloos Institute. Dr. Feemster received grant support and funding for research for this study from the VA HSR&D Fellowship. Dr. Burnham received travel support from NIH. NR 58 TC 14 Z9 14 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2013 VL 41 IS 6 BP 1518 EP 1525 DI 10.1097/CCM.0b013e318287f1bb PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 148TC UT WOS:000319269400035 PM 23538449 ER PT J AU Jin, J Phitayakorn, R Wilhelm, S McHenry, CR AF Jin, Judy Phitayakorn, Roy Wilhelm, Scott McHenry, Christopher R. TI Advances in management of thyroid cancer SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID FINE-NEEDLE-ASPIRATION; POSITRON-EMISSION-TOMOGRAPHY; RECOMBINANT HUMAN THYROTROPIN; DIFFUSE SCLEROSING VARIANT; RADIOACTIVE IODINE THERAPY; STIMULATING HORMONE-LEVEL; LYMPH-NODE DISSECTION; HYPERFRACTIONATED ACCELERATED RADIOTHERAPY; HISTONE DEACETYLASE INHIBITOR; SUFFICIENT SURGICAL-TREATMENT C1 [Jin, Judy] Cleveland Clin Fdn, Dept Endocrine Surg, Cleveland, OH 44195 USA. [Phitayakorn, Roy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wilhelm, Scott; McHenry, Christopher R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [McHenry, Christopher R.] Metrohlth Med Ctr, Cleveland, OH USA. RP Jin, J (reprint author), Cleveland Clin Fdn, Dept Endocrine Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA. OI Phitayakorn, Roy/0000-0002-8327-1484 NR 288 TC 5 Z9 7 U1 0 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 EI 1535-6337 J9 CURR PROB SURG JI Curr. Probl. Surg. PD JUN PY 2013 VL 50 IS 6 BP 241 EP 289 DI 10.1067/j.cpsurg.2013.02.001 PG 49 WC Surgery SC Surgery GA 149IG UT WOS:000319311600002 PM 23672743 ER PT J AU Le, XN Pugach, EK Hettmer, S Storer, NY Liu, JN Wills, AA DiBiase, A Chen, EY Ignatius, MS Poss, KD Wagers, AJ Langenau, DM Zon, LI AF Le, Xiuning Pugach, Emily K. Hettmer, Simone Storer, Narie Y. Liu, Jianing Wills, Airon A. DiBiase, Antony Chen, Eleanor Y. Ignatius, Myron S. Poss, Kenneth D. Wagers, Amy J. Langenau, David M. Zon, Leonard I. TI A novel chemical screening strategy in zebrafish identifies common pathways in embryogenesis and rhabdomyosarcoma development SO DEVELOPMENT LA English DT Article DE RAS; Embryogenesis; Rhabdomyosarcoma; Translational control; Zebrafish ID TRANSLATION INITIATION; TRANSGENIC ZEBRAFISH; CHLOROMETHYL KETONE; SIGNALING PATHWAYS; RAS ONCOGENES; MAP KINASE; IN-VIVO; CANCER; TARGETS; MTOR AB The zebrafish is a powerful genetic model that has only recently been used to dissect developmental pathways involved in oncogenesis. We hypothesized that operative pathways during embryogenesis would also be used for oncogenesis. In an effort to define RAS target genes during embryogenesis, gene expression was evaluated in Tg(hsp70-HRAS(G12V)) zebrafish embryos subjected to heat shock. dusp6 was activated by RAS, and this was used as the basis for a chemical genetic screen to identify small molecules that interfere with RAS signaling during embryogenesis. A KRAS(G12D)-induced zebrafish embryonal rhabdomyosarcoma was then used to assess the therapeutic effects of the small molecules. Two of these inhibitors, PD98059 and TPCK, had anti-tumor activity as single agents in both zebrafish embryonal rhabdomyosarcoma and a human cell line of rhabdomyosarcoma that harbored activated mutations in NRAS. PD98059 inhibited MEK1 whereas TPCK suppressed S6K1 activity; however, the combined treatment completely suppressed eIF4B phosphorylation and decreased translation initiation. Our work demonstrates that the activated pathways in RAS induction during embryogenesis are also important in oncogenesis and that inhibition of these pathways suppresses tumor growth. C1 [Le, Xiuning; Pugach, Emily K.; Storer, Narie Y.; DiBiase, Antony; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. [Le, Xiuning; Pugach, Emily K.; Storer, Narie Y.; DiBiase, Antony; Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Le, Xiuning; Pugach, Emily K.; Storer, Narie Y.; DiBiase, Antony; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. [Hettmer, Simone; Liu, Jianing; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Joslin Diabet Ctr, Howard Hughes Med Inst,Dept Stem Cell & Regenera, Boston, MA 02115 USA. [Wills, Airon A.; Poss, Kenneth D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Cell Biol, Durham, NC 27710 USA. [Chen, Eleanor Y.; Ignatius, Myron S.; Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. [Chen, Eleanor Y.; Ignatius, Myron S.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU National Institutes of Health [5 R01 CA103846-10, K01AR05562190, R01CA154923, R21CA156056, 1U54CA168512, RO1 HL088582-01S1, GM074057, HL081674]; Howard Hughes Medical Institute; American Cancer Society; Harvard Stem Cell Institute; Sarcoma Foundation of America; Alex Lemonade Stand Foundation; Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant [SU2C-AACR-IRG1111]; Hope Street Kids; P.A.L.S. FX L.I.Z. is supported by the National Institutes of Health [5 R01 CA103846-10] and Howard Hughes Medical Institute. D. M. L. is supported by the National Institutes of Health [K01AR05562190, R01CA154923, R21CA156056 and 1U54CA168512], The American Cancer Society, The Harvard Stem Cell Institute, The Sarcoma Foundation of America, and Alex Lemonade Stand Foundation. A.J.W. is supported by a Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant [SU2C-AACR-IRG1111] and the National Institutes of Health [RO1 HL088582-01S1]. K. D. P. is supported by the National Institutes of Health [GM074057 and HL081674]. S. H. is supported by Hope Street Kids and P.A.L.S. Bermuda/St. Baldrick's. Deposited in PMC for release after 6 months. NR 40 TC 21 Z9 22 U1 0 U2 13 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 1 PY 2013 VL 140 IS 11 BP 2354 EP 2364 DI 10.1242/dev.088427 PG 11 WC Developmental Biology SC Developmental Biology GA 145UK UT WOS:000319043400011 PM 23615277 ER PT J AU Altman, RK Danik, SB Barrett, CD AF Altman, Robert K. Danik, Stephan B. Barrett, Conor D. TI Uncontrolled forward motion of an ablation catheter through a recently available deflectable sheath SO EUROPACE LA English DT Editorial Material C1 [Altman, Robert K.; Danik, Stephan B.; Barrett, Conor D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Barrett, CD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM cdbarrett@partners.org OI Altman, Robert/0000-0002-1612-3561 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD JUN PY 2013 VL 15 IS 6 BP 786 EP 786 DI 10.1093/europace/eut008 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151NW UT WOS:000319468300008 PM 23362018 ER PT J AU Kuntz, J Gupta, R Schonberg, SO Semmler, W Kachelriess, M Bartling, S AF Kuntz, Jan Gupta, Rajiv Schoenberg, Stefan O. Semmler, Wolfhard Kachelriess, Marc Bartling, Soenke TI Real-time X-ray-based 4D image guidance of minimally invasive interventions SO EUROPEAN RADIOLOGY LA English DT Article DE Intervention guidance; 4D imaging; Compressed sensing; Catheter lab; Minimally invasive ID COMPRESSED SENSING PICCS; RECONSTRUCTION ALGORITHMS; CT FLUOROSCOPY; PERFORMANCE; RADIATION; SCANNER; BEAM AB A new technology is introduced that enables real-time 4D (three spatial dimensions plus time) X-ray guidance for vascular catheter interventions with acceptable levels of ionising radiation. The enabling technology is a combination of low-dose tomographic data acquisition with novel compressed sensing reconstruction and use of prior image information. It was implemented in a prototype set-up consisting of a gantry-based flat detector system. In pigs (n = 5) angiographic interventions were simulated. Radiation dosage on a per time base was compared with the "gold standard" of X-ray projection imaging. Contrary to current image guidance methods that lack permanent 4D updates, the spatial position of interventional instruments could be resolved in continuous, spatial 4D guidance; the movement of the guide wire as well as the expansion of stents could be precisely tracked in 3D angiographic road maps. Dose rate was 23.8 mu Gy/s, similar to biplane standard angiographic fluoroscopy, which has a dose rate of 20.6 mu Gy/s. Real-time 4D X-ray image-guidance with acceptable levels of radiation has great potential to significantly influence the field of minimally invasive medicine by allowing faster and safer interventions and by enabling novel, much more complex procedures for vascular and oncological minimally invasive therapy. aEuro cent Real-time 4D (three spatial dimensions plus time) angiographic intervention guidance is realistic. aEuro cent Low-dose tomographic data acquisition with special compressed sensing-based algorithms is enabled. aEuro cent Compared with 4D CT fluoroscopy, this method reduces radiation to acceptable levels. aEuro cent Once implemented, vascular interventions may become safer and faster. aEuro cent More complex intervention approaches may be developed. C1 [Kuntz, Jan; Semmler, Wolfhard; Kachelriess, Marc; Bartling, Soenke] German Canc Res Ctr, Dept Med Phys Radiol, D-69120 Heidelberg, Germany. [Gupta, Rajiv] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Schoenberg, Stefan O.; Bartling, Soenke] Heidelberg Univ, Med Fac Mannheim, Inst Clin Radiol & Nucl Med, D-68167 Mannheim, Germany. RP Bartling, S (reprint author), German Canc Res Ctr, Dept Med Phys Radiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM j.kuntz@dkfz.de; rgupta1@partners.org; stefan.schoenberg@umm.de; semmler.office@dkfz.de; marc.kachelriess@dkfz.de; soenkebartling@gmx.de OI Bartling, Sonke/0000-0001-5434-9433 FU DFG (German Research Foundation) [KA 1678/6-1, BA 3546/2-1]; Siemens Healthcare FX The research is funded by DFG (German Research Foundation) grant (KA 1678/6-1 and BA 3546/2-1) and Siemens Healthcare. We acknowledge Stefan Sawall's support in the creation of the reconstruction algorithm and his contribution to the discussion of the methodology. We thank Dr. Michaela Socher and Roland Galmbacher for animal handling. Furthermore, we would like to acknowledge Barbara Flach and Rolf Kueres for help during experimental set-ups and discussion of future developments. We would like to thank Dr. Michael Grasruck, Dr. Andreas Maier and Dr. Yiannis Kyriakou for extensive help with the experimental set-up, as well as discussion of applications, clinical implementation and future developments. NR 25 TC 4 Z9 4 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JUN PY 2013 VL 23 IS 6 BP 1669 EP 1677 DI 10.1007/s00330-012-2761-2 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 148TP UT WOS:000319270800025 PM 23314598 ER PT J AU Newmark, RE Schon, K Ross, RS Stern, CE AF Newmark, Randall E. Schon, Karin Ross, Robert S. Stern, Chantal E. TI Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory SO HIPPOCAMPUS LA English DT Article DE high-resolution fMRI; dentate gyrus; CA3; CA1; delayed match-to-sample ID MEDIAL TEMPORAL-LOBE; LONG-TERM-MEMORY; COMPLEMENTARY-LEARNING-SYSTEMS; HIGH-RESOLUTION FMRI; LAYER-III NEURONS; TO-SAMPLE TASK; DENTATE GYRUS; PATTERN SEPARATION; PERIRHINAL CORTEX; PERSISTENT ACTIVITY AB The hippocampus and medial temporal lobes (MTL) support the successful formation of new memories without succumbing to interference from related, older memories. Computational models and animal findings have implicated the dentate gyrus (DG), CA3, CA1, and entorhinal cortex (EC) in the disambiguation and encoding of well-established, episodic events that share common elements. However, it is unknown if these hippocampal subfields and MTL (entorhinal, perirhinal, parahippocampal) cortices also contribute during working memory when overlapping stimuli that share related features are rapidly encoded and subsequently maintained over a brief temporal delay. We hypothesized that activity in CA3/DG hippocampal subfields would be greater for the rapid encoding of stimuli with overlapping features than for the rapid encoding of stimuli with distinct features. In addition, we predicted that CA1 and EC, regions that are associated with creating long-term episodic representations, would show greater sustained activity across both encoding and delay periods for representations of stimuli with overlapping features than for those with distinct features. We used high-resolution fMRI during a delayed matching-to-sample (DMS) task using face pairs that either shared (overlapping condition, OL) or did not share (non-overlapping condition, NOL) common elements. We contrasted the OL condition with the NOL condition separately at sample (encoding) and during a brief delay (maintenance). At sample, we observed activity localized to CA3/DG, the subiculum, and CA1. At delay, we observed activity localized to the subiculum and CA1 and activity within the entorhinal, perirhinal, and parahippocampal cortices. Our findings are consistent with our hypotheses and suggest that CA3/DG, CA1 and the subiculum support the disambiguation and encoding of overlapping representations while CA1, subiculum and entorhinal cortex maintain these overlapping representations during working memory. (c) 2013 Wiley Periodicals, Inc. C1 [Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Boston Univ, Dept Psychol, Ctr Memory & Brain, Boston, MA 02215 USA. [Newmark, Randall E.; Stern, Chantal E.] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA. [Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Boston Univ, CELEST, Boston, MA 02215 USA. [Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Stern, CE (reprint author), Ctr Memory & Brain, 2 Cummington Mall,109, Boston, MA 02215 USA. EM chantal@bu.edu OI Schon, Karin/0000-0003-2963-8449; Ross, Robert/0000-0002-3987-881X FU National Science Foundation Science of Learning Center [NSF SMA-0835976, NSF SBE-0354378]; NIH NCRR; NCRR Biomedical Technology Program of the National Center for Research Resources [NIH S10RR021110, P41RR14075] FX Grant sponsor: National Science Foundation Science of Learning Center; Grant number: NSF SMA-0835976 and NSF SBE-0354378; Grant sponsors: NIH NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program and NCRR Biomedical Technology Program of the National Center for Research Resources; Grant numbers: NIH S10RR021110 and P41RR14075. NR 99 TC 20 Z9 20 U1 3 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PD JUN PY 2013 VL 23 IS 6 BP 467 EP 475 DI 10.1002/hipo.22106 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 149CJ UT WOS:000319295300005 PM 23504938 ER PT J AU Garvin, EC Cannuscio, CC Branas, CC AF Garvin, Eugenia C. Cannuscio, Carolyn C. Branas, Charles C. TI Greening vacant lots to reduce violent crime: a randomised controlled trial SO INJURY PREVENTION LA English DT Article ID NEIGHBORHOOD DISORDER; COLLECTIVE EFFICACY; INNER-CITY; FEAR; HEALTH; ENVIRONMENT; OUTCOMES; STRESS; INJURY; SPACES AB Background Vacant lots are often overgrown with unwanted vegetation and filled with trash, making them attractive places to hide illegal guns, conduct illegal activities such as drug sales and prostitution, and engage in violent crime. There is some evidence that greening vacant lots is associated with reductions in violent crime. Methods We performed a randomised controlled trial of vacant lot greening to test the impact of this intervention on police reported crime and residents' perceptions of safety and disorder. Greening consisted of cleaning the lots, planting grass and trees, and building a wooden fence around the perimeter. We randomly allocated two vacant lot clusters to the greening intervention or to the control status (no intervention). Administrative data were used to determine crime rates, and local resident interviews at baseline (n = 29) and at follow-up (n = 21) were used to assess perceptions of safety and disorder. Results Unadjusted difference-in-differences estimates showed a non-significant decrease in the number of total crimes and gun assaults around greened vacant lots compared with control. People around the intervention vacant lots reported feeling significantly safer after greening compared with those living around control vacant lots (p < 0.01). Conclusions In this study, greening was associated with reductions in certain gun crimes and improvements in residents' perceptions of safety. A larger randomised controlled trial is needed to further investigate the link between vacant lot greening and violence reduction. C1 [Garvin, Eugenia C.] Univ Penn, Perelman Sch Med, Robert Wood Johnson Clin Scholars, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.] Univ Penn, Perelman Sch Med, VA Ctr Hlth Equ Res & Promot, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Branas, Charles C.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Garvin, EC (reprint author), Univ Penn, Perelman Sch Med, Robert Wood Johnson Clin Scholars, 13th Fl Blockley Hall,423 Gaurdian Dr, Philadelphia, PA 19104 USA. EM eugenia.garvin@uphs.upenn.edu FU Robert Wood Johnson Health and Society Scholars Educational Fund FX This work was supported by a grant from the Robert Wood Johnson Health and Society Scholars Educational Fund (no grant number). The funders played no role in study design, data collection or data analysis. NR 40 TC 31 Z9 31 U1 6 U2 51 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD JUN PY 2013 VL 19 IS 3 BP 198 EP 203 DI 10.1136/injuryprev-2012-040439 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 147YS UT WOS:000319208700009 PM 22871378 ER PT J AU Peacock, ZS Lam, DK Cox, DP Schmidt, BL AF Peacock, Z. S. Lam, D. K. Cox, D. P. Schmidt, B. L. TI Metastatic epithelioid angiosarcoma to the mandible: report of a case and review of the literature SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review DE epithelioid angiosarcoma; mandibular condyle; vascular malignancy; renal cell carcinoma ID DIFFERENTIAL-DIAGNOSIS; HEMANGIOENDOTHELIOMA; CARCINOMA; BONE AB Angiosarcoma and its epithelioid variant are vascular malignancies that rarely affect the facial skeleton. Epithelioid angiosarcoma resembles carcinoma and can be difficult to diagnose. A case is presented of metastatic epithelioid angiosarcoma to the mandible from an angiosarcomatoid portion of renal carcinoma. The diagnostic challenge is outlined and the literature is reviewed. C1 [Peacock, Z. S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lam, D. K.] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA USA. [Cox, D. P.] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA. [Schmidt, B. L.] NYU, Dept Oral & Maxillofacial Surg, New York, NY USA. [Schmidt, B. L.] NYU, Bluestone Ctr Clin Res, New York, NY USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org OI Schmidt, Brian/0000-0002-2409-8984 NR 10 TC 4 Z9 4 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD JUN PY 2013 VL 42 IS 6 BP 702 EP 706 DI 10.1016/j.ijom.2013.02.005 PG 5 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 152NI UT WOS:000319538000003 PM 23499149 ER PT J AU Meschia, JF Worrall, BB Brown, RD Ay, H McArdle, PF Rundek, T Kittner, SJ AF Meschia, James F. Worrall, Bradford B. Brown, Robert D. Ay, Hakan McArdle, Patrick F. Rundek, Tatjana Kittner, Steven J. TI NINDS stroke genetics network (SiGN) experience with the causative classification system SO INTERNATIONAL JOURNAL OF STROKE LA English DT Letter C1 [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Worrall, Bradford B.] Univ Virginia, Charlottesville, VA USA. [Brown, Robert D.] Mayo Clin, Rochester, MN USA. [Ay, Hakan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McArdle, Patrick F.; Kittner, Steven J.] Univ Maryland, Baltimore, MD 21201 USA. [Rundek, Tatjana] Univ Miami, Miami, FL USA. RP Meschia, JF (reprint author), Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM meschia.james@mayo.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD JUN PY 2013 VL 8 IS 4 BP E9 EP E9 DI 10.1111/j.1747-4949.2012.00944.x PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 150NX UT WOS:000319398900003 PM 23692494 ER PT J AU Jeon, HJ Peng, DH Chua, HC Srisurapanont, M Fava, M Bae, JN Chang, SM Hong, JP AF Jeon, Hong Jin Peng, Daihui Chua, Hong Choon Srisurapanont, Manit Fava, Maurizio Bae, Jae-Nam Chang, Sung Man Hong, Jin Pyo TI Melancholic features and hostility are associated with suicidality risk in Asian patients with major depressive disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Melancholic; Suicidality; Hostility; Asian; Major depressive disorder ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; UNIPOLAR DEPRESSION; LIFETIME PREVALENCE; MENTAL-DISORDERS; ANGER ATTACKS; FLUOXETINE TREATMENT; ALCOHOL DEPENDENCE; MOOD DISORDERS; DSM-IV; IDEATION AB Background: Suicide rates are higher in East-Asians than other populations, and especially high in Koreans. However, little is known about suicidality risk and melancholic features in Asian patients with major depressive disorder (MDD). Method: Drug-free MDD outpatients were included from 13 centers across five ethnicities consisting of Chinese (n = 290), Korean (n = 101), Thai (n = 102), Indian (n = 27), and Malay (n = 27). All were interviewed using the Mini-International Neuropsychiatric Interview (MINI.), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Symptoms Checklist 90-Revised (SCL-90-R). Results: Of 547 subjects, 177 MDD patients showed melancholic features (32.4%). These melancholic MDD patients revealed significantly higher suicidality risk (p < 0.0001), hostility (p = 0.037), and severity of depression (p < 0.0001) than those MDD patients without melancholic features. Suicidality risk was significantly higher in MDD with melancholic features than those without in subjects with lower hostility, whereas it showed no difference in higher hostility. Adjusted odds ratios of melancholic features and hostility for moderate to high suicidality risk were 1.79 (95% CI = 1.15-2.79) and 2.45 (95% CI = 1.37-4.38), after adjusting for age, sex, education years, and depression severity. Post-hoc analyses showed that suicidality risk was higher in Korean and Chinese than that of Thai, Indian and Malay in MDD subjects with melancholic features, although depression severity showed no significant differences among the ethnicities. Conclusions: Suicidality risk is associated with both melancholic features and hostility and it shows cross-ethnic differences in Asian MDD patients, independent of depression severity. (c) 2013 Elsevier B.V. All rights reserved. C1 [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Peng, Daihui] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Chua, Hong Choon] Inst Mental Hlth, Dept Psychiat, Singapore, Singapore. [Srisurapanont, Manit] Chiang Mai Univ, Dept Psychiat, Chiang Mai 50000, Thailand. [Bae, Jae-Nam] Inha Univ, Dept Psychiat, Coll Med, Inchon, South Korea. [Chang, Sung Man] Kyungpook Natl Univ, Dept Psychiat, Sch Med, Taegu, South Korea. RP Hong, JP (reprint author), Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, 388-1 Pungnap 2Dong, Seoul 138736, South Korea. EM jphong@amc.seoul.kr OI Bae, Jae Nam/0000-0002-5024-6231; Srisurapanont, Manit/0000-0001-6203-1206 FU Lundbeck; Duke-National University of Singapore Office of Clinical Research; Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2011-0013064] FX This work was supported by Lundbeck and the Duke-National University of Singapore Office of Clinical Research. Neither had a further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; This study was supported by an unrestricted research grants from Lundbeck and from the Duke-National University of Singapore Office of Clinical Research. This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064). We thank Aya Inamori, Research Assistant at the MGH Depression Clinical and research Program for reviewing this manuscript. NR 34 TC 14 Z9 15 U1 3 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN PY 2013 VL 148 IS 2-3 BP 368 EP 374 DI 10.1016/j.jad.2013.01.001 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 143ZX UT WOS:000318909700029 PM 23414572 ER PT J AU Schwartz, AV Schafer, AL Grey, A Vittinghoff, E Palermo, L Lui, LYL Wallace, RB Cummings, SR Black, DM Bauer, DC Reid, IR AF Schwartz, Ann V. Schafer, Anne L. Grey, Andrew Vittinghoff, Eric Palermo, Lisa Lui, Li-Yung L. Wallace, Robert B. Cummings, Steven R. Black, Dennis M. Bauer, Douglas C. Reid, Ian R. TI Effects of antiresorptive therapies on glucose metabolism: Results from the FIT, HORIZON-PFT, and FREEDOM trials SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ANTIRESORPTIVE THERAPY; GLUCOSE; DIABETES; WEIGHT ID FRACTURE INTERVENTION TRIAL; POSTMENOPAUSAL OSTEOPOROTIC WOMEN; YEARLY ZOLEDRONIC ACID; BONE TURNOVER; OLDER MEN; UNDERCARBOXYLATED OSTEOCALCIN; BIOCHEMICAL MARKERS; VERTEBRAL FRACTURES; INSULIN-RESISTANCE; ENERGY-METABOLISM AB In rodent models, undercarboxylated osteocalcin (ucOC) acts as a hormone that promotes insulin sensitivity and secretion. If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes. We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N=6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N=7113) of zoledronic acid (3 years), and Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N=7076) of denosumab (3 years). Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM in all participants. Weight was measured annually in all trials. Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose. Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant: 0.47mg/dL in FIT, 0.20mg/dL in HORIZON-PFT, and 0.09mg/dL in FREEDOM, all p>0.6. Weight change differed between treatment and placebo groups in FIT (0.32kg, p=0.003) and FREEDOM (0.31kg, p=0.023) but not in HORIZON-PFT (0.15kg, p=0.132). In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively. Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (pooled relative risk [RR]=0.90; 95% confidence interval [CI] 0.741.10). Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight, or diabetes risk in postmenopausal women. Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans. C1 [Schwartz, Ann V.; Schafer, Anne L.; Vittinghoff, Eric; Palermo, Lisa; Black, Dennis M.; Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94107 USA. [Schafer, Anne L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Grey, Andrew; Reid, Ian R.] Univ Auckland, Auckland 1, New Zealand. [Lui, Li-Yung L.; Cummings, Steven R.] Calif Pacific Med Ctr, San Francisco, CA USA. [Wallace, Robert B.] Univ Iowa, Iowa City, IA USA. RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA. EM aschwartz@psg.ucsf.edu FU Department of Veterans Affairs [5 IK2 CX000549-02]; Merck Co., Inc.; Novartis Pharma; Amgen Inc. FX ALS was supported by a career development award from the Department of Veterans Affairs (5 IK2 CX000549-02). The clinical trials were supported by their respective sponsors. The Fracture Intervention Trial was sponsored by Merck & Co., Inc.; Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) was sponsored by Novartis Pharma; and the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 months (FREEDOM) trial was sponsored by Amgen Inc. This study was not financially supported by the trial sponsors. NR 36 TC 40 Z9 41 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2013 VL 28 IS 6 BP 1348 EP 1354 DI 10.1002/jbmr.1865 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149VS UT WOS:000319350100013 PM 23322676 ER PT J AU Komatsu, Y Yu, PB Kamiya, N Pan, HC Fukuda, T Scott, GJ Ray, MK Yamamura, K Mishina, Y AF Komatsu, Yoshihiro Yu, Paul B. Kamiya, Nobuhiro Pan, Haichun Fukuda, Tomokazu Scott, Gregory J. Ray, Manas K. Yamamura, Ken-ichi Mishina, Yuji TI Augmentation of smad-dependent BMP signaling in neural crest cells causes craniosynostosis in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BMP; CRANIOSYNOSTOSIS; NEURAL CREST CELLS; SMAD-SIGNALING; SUTURE ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; CALVARIAL BONE-DEVELOPMENT; SKULL VAULT; I RECEPTOR; OSTEOBLAST APOPTOSIS; SUTURE DEVELOPMENT; MOUSE MODEL; KAPPA-B; FGF; GROWTH AB Craniosynostosis describes conditions in which one or more sutures of the infant skull are prematurely fused, resulting in facial deformity and delayed brain development. Approximately 20% of human craniosynostoses are thought to result from gene mutations altering growth factor signaling; however, the molecular mechanisms by which these mutations cause craniosynostosis are incompletely characterized, and the causative genes for diverse types of syndromic craniosynostosis have yet to be identified. Here, we show that enhanced bone morphogenetic protein (BMP) signaling through the BMP type IA receptor (BMPR1A) in cranial neural crest cells, but not in osteoblasts, causes premature suture fusion in mice. In support of a requirement for precisely regulated BMP signaling, this defect was rescued on a Bmpr1a haploinsufficient background, with corresponding normalization of Smad phosphorylation. Moreover, in vivo treatment with LDN-193189, a selective chemical inhibitor of BMP type I receptor kinases, resulted in partial rescue of craniosynostosis. Enhanced signaling of the fibroblast growth factor (FGF) pathway, which has been implicated in craniosynostosis, was observed in both mutant and rescued mice, suggesting that augmentation of FGF signaling is not the sole cause of premature fusion found in this model. The finding that relatively modest augmentation of Smad-dependent BMP signaling leads to premature cranial suture fusion suggests an important contribution of dysregulated BMP signaling to syndromic craniosynostoses and potential strategies for early intervention. C1 [Komatsu, Yoshihiro; Kamiya, Nobuhiro; Pan, Haichun; Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Komatsu, Yoshihiro; Kamiya, Nobuhiro; Fukuda, Tomokazu; Mishina, Yuji] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Yu, Paul B.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Yu, Paul B.] Harvard Univ, Sch Med, Boston, MA USA. [Kamiya, Nobuhiro] Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA. [Fukuda, Tomokazu] Tohoku Univ, Grad Sch Agr Sci, Sendai, Miyagi 980, Japan. [Scott, Gregory J.; Ray, Manas K.; Mishina, Yuji] NIEHS, Knock Out Core, NIH, Res Triangle Pk, NC 27709 USA. [Yamamura, Ken-ichi] Kumamoto Univ, Inst Mol Embryol & Genet, Kumamoto, Japan. RP Mishina, Y (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 North Univ Ave, Ann Arbor, MI 48109 USA. EM mishina@umich.edu OI Yu, Paul/0000-0003-2145-4944 FU National Institutes of Health [K99DE021054, K08HL079943, R01AR057374, R01DE020843, ES071003-11]; Japan Society for the Promotion of Science FX This study was supported by the National Institutes of Health (K99DE021054 to YK; K08HL079943 and R01AR057374 to PBY; and R01DE020843 and ES071003-11 to YM) and a fellowship from the Japan Society for the Promotion of Science (YK). NR 55 TC 16 Z9 16 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2013 VL 28 IS 6 BP 1422 EP 1433 DI 10.1002/jbmr.1857 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149VS UT WOS:000319350100020 PM 23281127 ER PT J AU Hashash, JG Nasr, JY Francis, F AF Hashash, J. G. Nasr, J. Y. Francis, Fadi TI Gastrointestinal: Mucinous and signet cell adenocarcinoma of the appendix SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article C1 [Hashash, J. G.; Nasr, J. Y.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. [Francis, Fadi] VA Pittsburgh Healthcare Syst, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. RP Hashash, JG (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JUN PY 2013 VL 28 IS 6 BP 903 EP 903 DI 10.1111/jgh.12226 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149RX UT WOS:000319339900004 PM 23692577 ER PT J AU de Mena, L Samaranch, L Coto, E Cardo, LF Ribacoba, R Lorenzo-Betancor, O Pastor, P Wang, L Irigoyen, J Mata, IF Diaz, M Moris, G Menendez, M Corao, AI Lorenzo, E Alvarez, V AF de Mena, Lorena Samaranch, LLuis Coto, Eliecer Cardo, Lucia F. Ribacoba, Rene Lorenzo-Betancor, Oswaldo Pastor, Pau Wang, Li Irigoyen, Jaione Mata, Ignacio F. Diaz, Marta Moris, German Menendez, Manuel Corao, Ana I. Lorenzo, Elena Alvarez, Victoria TI Mutational Screening of PARKIN Identified a 3 ' UTR Variant (rs62637702) Associated with Parkinson's Disease SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 11th International Symposium on VIP, PACAP and Related Peptides CY AUG 27-31, 2013 CL Univ Pecs, Pecs, HUNGARY HO Univ Pecs DE Parkinson's disease; Parkin; Mutation; DNA polymorphisms; Genetic risk; Genetics ID ALPHA-SYNUCLEIN EXPRESSION; RISK; GENE AB PRKN mutations have been linked to Parkinson's disease (PD). Most of the mutational screenings have focused on the coding exons. The 3' untranslated region (UTR) could also harbor functionally relevant nucleotide changes. We performed a mutational screening of PRKN in a cohort of early-onset PD patients (n = 235) from Spain. We found 16 mutations (five new): 16 patients (7 %) carried two mutations and only one mutation was found in 28 (12 %). Patients with two mutations had significantly lower mean age (30 +/- 9 years) compared to patients with one (40 +/- 7) or no mutation (42 +/- 7). We found a total of 15 nucleotide variants (three new) in the 3' UTR region. The frequency of carriers of the rare rs62637702 G allele (*94A/G) was significantly lower among the patients compared to healthy controls (n = 418) (0.03 vs. 0.004; p < 0.001), suggesting a protective role for this allele. In order to investigate the basal effect of this variant, we performed luciferase assays. No different basal activity was observed between the two alleles. In conclusion, the rs62637702 polymorphism was associated with PD. This could be a surrogate marker for disease risk, in linkage disequilibrium with other non-identified functional variant. C1 [de Mena, Lorena; Coto, Eliecer; Cardo, Lucia F.; Diaz, Marta; Corao, Ana I.; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo, Spain. [Samaranch, LLuis; Lorenzo-Betancor, Oswaldo; Pastor, Pau; Irigoyen, Jaione; Lorenzo, Elena] Univ Navarra, CIMA, Ctr Appl Med Res, Neurogenet Lab,Div Neurosci, E-31080 Pamplona, Spain. [Ribacoba, Rene; Moris, German; Menendez, Manuel] Hosp Univ Cent Asturias, Asturias, Spain. [Ribacoba, Rene; Moris, German; Menendez, Manuel] Hosp Univ Alvarez Buylla Mieres, Asturias, Spain. [Coto, Eliecer] Univ Oviedo, Dept Med, Oviedo, Spain. [Lorenzo-Betancor, Oswaldo; Pastor, Pau; Irigoyen, Jaione; Lorenzo, Elena] Univ Navarra, Sch Med, Clin Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain. [Wang, Li] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA. [Wang, Li] Univ Utah, Sch Med, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA. [Mata, Ignacio F.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Mata, Ignacio F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Alvarez, Victoria] Hosp Cent Asturias Maternidad, Oviedo 33006, Spain. RP Alvarez, V (reprint author), Hosp Cent Asturias Maternidad, Oviedo 33006, Spain. EM victoria.alvarez@sespa.princast.es RI Pastor, Pau/C-9834-2009; OI Pastor, Pau/0000-0002-7493-8777; Moris, German/0000-0001-7608-2194; Fernandez Mata, Ignacio/0000-0003-1198-0633 FU Spanish Fondo de Investigaciones Sanitarias-Fondos FEDER European Union [FIS-05/008, 08/0915, 11/0093]; FICYT-Principado de Asturias; Spanish Ministry of Science and Technology; European Social Fund; Spanish Ministry of Education and Science [SAF2006-10126]; Fundacio La Marato de TV3 [061131]; UTE project FIMA, Spain; Fundacion Parkinson Asturias; Obra Social Cajastur FX The authors thank the Fundacion Parkinson Asturias and Obra Social Cajastur for their support. This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias-Fondos FEDER European Union (FIS-05/008, 08/0915, and 11/0093). LFC and LDM are predoctoral fellowships of FICYT-Principado de Asturias. LS held a Torres Quevedo fellowship from the Spanish Ministry of Science and Technology, co-financed by the European Social Fund. This study was supported by a grant from the Spanish Ministry of Education and Science (SAF2006-10126: 2006-2009), by the project 061131 from the Fundacio La Marato de TV3 and by the UTE project FIMA, Spain to PP. We thank all participating subjects and their relatives for their contribution to the study. We thank Drs. Maria A. Pastor, Jose Obeso, Maria R Luquin, Maria C Rodriguez-Oroz, and Mario Riverol for recruiting some subjects for the study. NR 21 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JUN PY 2013 VL 50 IS 2 BP 264 EP 269 DI 10.1007/s12031-012-9942-y PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 148UX UT WOS:000319274200005 PM 23275044 ER PT J AU Saria, MG Corle, C Hu, J Rudnick, JD Phuphanich, S Mrugala, MM Crew, LK Bota, DA Fu, BD Kim, RY Brown, T Feely, H Brechlin, J Brown, BD Drappatz, J Wen, PY Chen, CC Carter, B Lee, JW Kesari, S AF Saria, Marlon G. Corle, Courtney Hu, Jethro Rudnick, Jeremy D. Phuphanich, Surasak Mrugala, Maciej M. Crew, Laura K. Bota, Daniela A. Fu, Beverly Dan Kim, Ryan Y. Brown, Tiffany Feely, Homira Brechlin, Joanne Brown, Bradley D. Drappatz, Jan Wen, Patrick Y. Chen, Clark C. Carter, Bob Lee, Jong Woo Kesari, Santosh TI Retrospective analysis of the tolerability and activity of lacosamide in patients with brain tumors SO JOURNAL OF NEUROSURGERY LA English DT Article DE seizure; antiepileptic drug; primary brain tumor; oncology ID EPILEPSY; MANAGEMENT; SEIZURES AB Object. The object of this study was to determine the tolerability and activity of lacosamide in patients with brain tumors. Methods. The authors reviewed the medical records at 5 US academic medical centers with tertiary brain tumor programs, seeking all patients in whom a primary brain tumor had been diagnosed and who were taking lacosamide. Results. The authors identified 70 patients with primary brain tumors and reviewed seizure frequency and toxicities. The majority of the patients had gliomas (96%). Fifty-five (78%) had partial seizures only, and 12 (17%) had generalized seizures. Most of the patients (74%) were started on lacosamide because of recurrent seizures. Forty-six patients (66%) reported a decrease in seizure frequency, and 21 patients (30%) reported stable seizures. Most of the patients (54 [77%]) placed on lacosamide did not report any toxicities. Conclusions. This retrospective analysis demonstrated that lacosamide was both well tolerated and active as an add-on antiepileptic drug (AED) in patients with brain tumors. Lacosamide's novel mechanism of action will allow for concurrent use with other AEDs, as documented by its activity across many different types of AEDs used in this patient population. Larger prospective studies are warranted. C1 [Saria, Marlon G.; Corle, Courtney; Kim, Ryan Y.; Brown, Tiffany; Feely, Homira; Brechlin, Joanne; Brown, Bradley D.; Kesari, Santosh] Univ Calif San Diego, Moores Canc Ctr, Dept Neurosci, La Jolla, CA 92093 USA. [Feely, Homira; Chen, Clark C.; Carter, Bob] Univ Calif San Diego, Moores Canc Ctr, Dept Neurosurg, La Jolla, CA 92093 USA. [Hu, Jethro; Rudnick, Jeremy D.; Phuphanich, Surasak] Cedars Sinai Med Ctr, Dept Neurol & Neurosurg, Cochran Brain Tumor Ctr, Los Angeles, CA USA. [Bota, Daniela A.; Fu, Beverly Dan] Univ Calif Irvine, Sch Med, Dept Neurol, Irvine, CA 92717 USA. [Bota, Daniela A.] Univ Calif Irvine, Sch Med, Dept Neurol Surg, Irvine, CA 92717 USA. [Bota, Daniela A.] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Irvine, CA 92717 USA. [Mrugala, Maciej M.] Univ Washington, Dept Neurol, Sch Med, Seattle, WA USA. [Crew, Laura K.] Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. [Mrugala, Maciej M.; Crew, Laura K.] Univ Washington, Sch Med, Neurooncol Ctr, Seattle, WA 98195 USA. [Drappatz, Jan; Wen, Patrick Y.; Lee, Jong Woo] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Drappatz, Jan; Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kesari, S (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM skesari@ucsd.edu RI Kesari, Santosh/E-8461-2013 FU NIH [3P30CA023100-25S8]; American Cancer Society; NM; Novartis; Merck; Bristol Meyers Squibb FX This work was supported in part by NIH Grant No. 3P30CA023100-25S8 (S.K.). Dr. Mrugala is on the speakers' bureau of and is a consultant for UCB Pharma. Dr. Bota serves on the speakers' bureau of Merck, Roche, and Eisai; serves on the clinical advisory board of Epitopoietic Research Corp.; has received research support from the American Cancer Society; and receives institutional support from the University of California, Irvine, for stem cell research. Dr. Kesari is on the speakers' bureau of UCB Pharma, Genentech, and Merck and has received research support from the NM, Novartis, Merck, and Bristol Meyers Squibb. NR 14 TC 12 Z9 12 U1 0 U2 5 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 2013 VL 118 IS 6 BP 1183 EP 1187 DI 10.3171/2013.1.JNS12397 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 150BY UT WOS:000319366400008 PM 23451905 ER PT J AU Elder, JB Chiocca, EA AF Elder, J. Bradley Chiocca, E. Antonio TI Glioblastoma multiforme and laser interstitial thermal therapy SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID METASTASES; LIVER; AGE C1 [Elder, J. Bradley] Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Elder, JB (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 2013 VL 118 IS 6 BP 1199 EP 1200 DI 10.3171/2012.9.JNS121563 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 150BY UT WOS:000319366400012 PM 23560576 ER PT J AU Duhaime, AC Stufflebeam, SM AF Duhaime, Ann-Christine Stufflebeam, Steven M. TI Connectivity via magnetoencephalography SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID IMAGING APPROACH; MILD; MEG C1 [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. [Stufflebeam, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 2013 VL 118 IS 6 BP 1304 EP 1305 DI 10.3171/2012.10.JNS121408 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 150BY UT WOS:000319366400029 PM 23600936 ER PT J AU Yoon, MK Parsa, AT Horton, JC AF Yoon, Michael K. Parsa, Andrew T. Horton, Jonathan C. TI Skull thickening, paranasal sinus expansion, and sella turcica shrinkage from chronic intracranial hypotension SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE enophthalmos; ventriculoperitoneal shunt; cerebrospinal fluid; hydrocephalus; pneumocephalus; Sunken Eyes, Sagging Brain Syndrome ID BILATERAL ENOPHTHALMOS; BRAIN-SYNDROME; HYDROCEPHALUS; SHUNTS; MANAGEMENT; PRESSURE; VALVE AB In children or young adults, the morphology of the skull can be altered by excessive drainage of CSF following placement of a ventriculoperitoneal (VP) shunt. In Sunken Eyes, Sagging Brain Syndrome, gradual enlargement of the orbital cavity occurs from low or negative intracranial pressure (ICP), leading to progressive bilateral enophthalmos. The authors report several heretofore unrecognized manifestations of this syndrome, which developed in a 29-year-old man with a history of VP shunt placement following a traumatic brain injury at the age of 9 years. Magnetic resonance imaging showed typical features of chronic intracranial hypotension, and lumbar puncture yielded an unrecordable subarachnoid opening pressure. The calvaria was twice its normal thickness, owing to contraction of the inner table. The paranasal sinuses were expanded, with aeration of the anterior clinoid processes, greater sphenoid wings, and temporal bones. The sella turcica showed a 50% reduction in cross-sectional area as compared with that in control subjects, resulting in partial extrusion of the pituitary gland. These new features broaden the spectrum of clinical findings associated with low ICP. Secondary installation of a valve to restore normal ICP is recommended to halt progression of these rare complications of VP shunt placement. C1 [Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Parsa, Andrew T.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Horton, Jonathan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Horton, Jonathan C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Horton, Jonathan C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. RP Horton, JC (reprint author), Univ Calif San Francisco, 10 Koret Way, San Francisco, CA 94143 USA. EM hortonj@vision.ucsf.edu FU National Eye Institute [EY10217]; Research to Prevent Blindness FX This work was supported by National Eye Institute Grant No. EY10217 and Research to Prevent Blindness. NR 33 TC 3 Z9 3 U1 1 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD JUN PY 2013 VL 11 IS 6 BP 667 EP 672 DI 10.3171/2013.2.PEDS12560 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 150CD UT WOS:000319366900009 PM 23540524 ER PT J AU Knobe, M Gradl, G Maier, KJ Drescher, W Jansen-Troy, A Prescher, A Knechtel, T Antony, P Pape, HC AF Knobe, Matthias Gradl, Gertraud Maier, Klaus-Juergen Drescher, Wolf Jansen-Troy, Arne Prescher, Andreas Knechtel, Toralf Antony, Pia Pape, Hans-Christoph TI Rotationally Stable Screw-Anchor Versus Sliding Hip Screw Plate Systems in Stable Trochanteric Femur Fractures: A Biomechanical Evaluation SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE helical blade; hip screw; rotationally stable screw-anchor; biomechanical testing; trochanteric fracture; cutout; migration ID UNSTABLE INTERTROCHANTERIC FRACTURES; PERCUTANEOUS COMPRESSION PLATE; HELICAL BLADE; INTRAMEDULLARY NAIL; CUTOUT RESISTANCE; CANCELLOUS BONE; FEMORAL-NECK; LAG SCREWS; FIXATION; IMPLANT AB Objectives: The rotationally stable screw-anchor plate system (RoSA) is unique in using a novel screw-blade combination. This investigation tested the hypothesis whether RoSA is advantageous over the sliding hip screw plate system (SHS) with regard to stiffness, failure load, displacement, and migration in stable trochanteric femur fractures (OTA 31A1.1). Methods: Thirteen femur pairs (mean age = 79 years; range, 64-92 years) received implants of either the RoSA or SHS (Koenigsee Implants, Allendorf, Germany). Beginning with 300 N and under consecutive 300 N load-increase steps (2000 cycles, 0.5 Hz) the femurs were cycled until failure. Specimens were evaluated for fragment displacement in both frontal and rotational planes and for migration. A survival analysis was carried out. Results: With regard to stiffness (526 +/- 195 N/mm vs 358 +/- 143 N/mm; P = 0.006) and the failure load (2838 +/- 781 N vs 2262 +/- 863 N; P = 0.012), the RoSA proved superior to the SHS. Furthermore, RoSA demonstrated higher rotational stability in comparison to the SHS (1800 N: 0 +/- 0 degrees vs 1.1 +/- 1.3 degrees; P = 0.015; failure point: 0 + 0 degrees vs 2.3 + 2.6 degrees; P = 0.008), measuring rotation about femoral neck axis over time. Whereas cutout occurred only in the RoSA system (n = 3; P = 0.110), the SHS underwent plastic deformation in 7 cases (n = 7; P = 0.003). In one case (7%), the insertion of the RoSA blade resulted in iatrogenic cut-through caused by a jamming of the screw and the blade. Conclusions: The fixation of stable trochanteric femur fractures with RoSA in cadavers led to greater primary stability under cyclic load, with significant advantages with regard to stiffness, failure load, and rotational stability, compared with the SHS. A detrimental effect was its migration tendency, which began at 1800 N and occurred in the cranial direction. A meticulous insertion technique was a prerequisite to avoid iatrogenic perforation of the femoral head. Our results will have to be substantiated by further biomechanical and clinical trials using an optimized RoSA system. C1 [Knobe, Matthias; Knechtel, Toralf; Antony, Pia; Pape, Hans-Christoph] Univ Aachen, Med Ctr, Dept Orthopaed Trauma, D-52074 Aachen, Germany. [Gradl, Gertraud] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Maier, Klaus-Juergen] RoMed Hosp, Dept Surg, Bad Aibling, Germany. [Drescher, Wolf] Univ Aachen, Med Ctr, Dept Orthopaed Surg, D-52074 Aachen, Germany. [Jansen-Troy, Arne] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn, Aachen, Germany. [Prescher, Andreas] Univ Aachen, Med Ctr, Dept Mol & Cellular Anat, D-52074 Aachen, Germany. RP Knobe, M (reprint author), Univ Aachen, Med Ctr, Dept Orthopaed & Trauma Surg, 30 Pauwels St, D-52074 Aachen, Germany. EM mknobe@ukaachen.de NR 39 TC 3 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD JUN PY 2013 VL 27 IS 6 BP E127 EP E136 DI 10.1097/BOT.0b013e318278112a PG 10 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 151GA UT WOS:000319447500001 PM 23114419 ER PT J AU Yankeelov, TE Peterson, TE Abramson, RG Izquierdo-Garcia, D Arlinghaus, LR Li, X Atuegwu, NC Catana, C Manning, HC Fayad, ZA Gore, JC AF Yankeelov, Thomas E. Peterson, Todd E. Abramson, Richard G. Izquierdo-Garcia, David Arlinghaus, Lori R. Li, Xia Atuegwu, Nkiruka C. Catana, Ciprian Manning, H. Charles Fayad, Zahi A. Gore, John C. TI Simultaneous PET-MRI in oncology: A solution looking for a problem (vol 30, pg 1342, 2012) SO MAGNETIC RESONANCE IMAGING LA English DT Correction C1 [Yankeelov, Thomas E.; Peterson, Todd E.; Abramson, Richard G.; Arlinghaus, Lori R.; Li, Xia; Atuegwu, Nkiruka C.; Manning, H. Charles; Gore, John C.] Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37232 USA. [Yankeelov, Thomas E.; Peterson, Todd E.; Abramson, Richard G.; Arlinghaus, Lori R.; Li, Xia; Atuegwu, Nkiruka C.; Manning, H. Charles; Gore, John C.] Vanderbilt Univ, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. [Yankeelov, Thomas E.; Peterson, Todd E.; Gore, John C.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37232 USA. [Yankeelov, Thomas E.; Manning, H. Charles; Gore, John C.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA. [Yankeelov, Thomas E.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. [Izquierdo-Garcia, David; Fayad, Zahi A.] Mt Sinai Med Ctr, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Izquierdo-Garcia, David] Mt Sinai Med Ctr, Dept Radiol, New York, NY 10029 USA. [Catana, Ciprian] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Catana, Ciprian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Manning, H. Charles] Vanderbilt Univ, Dept Neurosurg, Nashville, TN 37232 USA. [Fayad, Zahi A.] Mt Sinai Med Ctr, Dept Cardiol, New York, NY 10029 USA. [Gore, John C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Yankeelov, TE (reprint author), Vanderbilt Univ, Med Ctr, Inst Imaging Sci, Med Ctr AA 1105, Nashville, TN 37232 USA. EM thomas.yankeelov@vanderbilt.edu NR 1 TC 1 Z9 1 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JUN PY 2013 VL 31 IS 5 BP 796 EP 796 DI 10.1016/j.mri.2013.01.015 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146PM UT WOS:000319103000023 ER PT J AU Hausmann, LRM Gao, S Mor, MK Schaefer, JH Fine, MJ AF Hausmann, Leslie R. M. Gao, Shasha Mor, Maria K. Schaefer, James H., Jr. Fine, Michael J. TI Understanding Racial and Ethnic Differences in Patient Experiences With Outpatient Health Care in Veterans Affairs Medical Centers SO MEDICAL CARE LA English DT Article DE race and ethnicity; disparities; CAHPS; health care experiences; Veterans ID UNITED-STATES; MANAGED CARE; SATISFACTION; DISPARITIES; ASSESSMENTS; RACE/ETHNICITY; PERCEPTIONS; PROVIDERS AB Background: Racial and ethnic differences in patient health care experiences have not been well examined in the Veterans Affairs (VA) Healthcare System. Objectives: To examine racial/ethnic differences in outpatient health care experiences within and between VA medical facilities. Research Design: We assessed within-facility and between-facility racial/ethnic differences in responses to the 2010 VA Survey of Healthcare Experiences of Patients using mixed-effects multinomial regression. Subjects: A total of 211,459 respondents (53.2%) to a random survey of outpatients from 910 VA medical facilities (71.9% non-Hispanic white, 15.1% non-Hispanic black, 6.4% Hispanic, and 6.7% Other race/ethnicity). Measures: Negative and positive patient-reported experiences in 8 domains of health care. Results: Between-facility effects for black race were higher for 7 domains of negative experiences [risk differences (RDs): 0.37% to 1.64%] and lower for 6 domains of positive experiences (RDs: -0.69% to -2.54%). Between-facility effects for Hispanic ethnicity were higher for 5 domains of negative experiences (RDs: 0.60%-1.34%) and lower for 5 domains of positive experiences (RDs: -1.00% to -1.88%). Hispanic ethnicity was also associated with higher within-facility rates of positive experiences for 5 domains of care (RDs: 2.97%-4.08%). Other race/ethnicity was associated with significantly higher within-facility rates of negative experiences (RDs: 2.04%-3.95%) and lower rates of positive experiences for all 8 domains (RDs: -2.05% to -4.70%). Conclusions: In a national random sample of Veterans managed in the VA Healthcare System, we demonstrated significant within-facility and between-facility racial and ethnic differences in outpatient health care experiences, with differing patterns for each minority group. C1 [Hausmann, Leslie R. M.; Gao, Shasha; Mor, Maria K.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hausmann, Leslie R. M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Schaefer, James H., Jr.] Off Informat & Analyt, Dept Vet Affairs, Durham, NC USA. RP Hausmann, LRM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com FU Center for Health Equity Research and Promotion (CHERP) VISN4 Pilot Research Program [LIP 72-051]; Veterans Affairs Health Services Research and Development Career Development Program [RCD 06-287] FX Supported by the Center for Health Equity Research and Promotion (CHERP) VISN4 Pilot Research Program (LIP 72-051). L.R.M.H.'s effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287). NR 33 TC 14 Z9 14 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2013 VL 51 IS 6 BP 532 EP 539 DI 10.1097/MLR.0b013e318287d6e5 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 145VD UT WOS:000319045800010 PM 23673395 ER PT J AU Iezzoni, LI Yu, J Wint, AJ Smeltzer, SC Ecker, JL AF Iezzoni, Lisa I. Yu, Jun Wint, Amy J. Smeltzer, Suzanne C. Ecker, Jeffrey L. TI Prevalence of Current Pregnancy Among US Women With and Without Chronic Physical Disabilities SO MEDICAL CARE LA English DT Article DE disability; pregnancy; movement difficulties; National Health Interview Survey ID HEALTH-CARE; MOTHERHOOD; EXPERIENCES AB Background: The number of US women of childbearing age who have chronic physical disabilities (CPD) is increasing. However, little is known about their reproductive experiences. Historically, women with physical disabilities have confronted stigmatized attitudes about becoming pregnant. Objectives: To explore the national prevalence of current pregnancy among women with and without CPD; examine differences in current pregnancy prevalence between these 2 groups of women. Research Design: Bivariable and multivariable analyses of cross-sectional, nationally representative National Health Interview Survey data from 2006 to 2011. Subjects: Forty-seven thousand six hundred twenty-nine civilian, noninstitutionalized women aged 18-49 years. Measures: National Health Interview Survey asks women ages 18-49 if they are currently pregnant; it also asks about various movement difficulties. We used responses from 8 movement difficulty and other questions to identify women with CPD. Results: Six thousand forty-three (12.7%) sampled women report CPD. Compared with other women, women with CPD are significantly: older; more likely to be black and less likely to be Asian or Hispanic; more likely to be divorced or separated; more likely to have less than a high school education; less likely to be employed; and have much lower incomes. Across all women, 3.5% report being currently pregnant: 3.8% of women without CPD and 2.0% with CPD. Controlling for sociodemographic factors, the adjusted odds ratio (95% confidence interval) of current pregnancy is 0.83 (95% confidence interval, 0.65-1.05; P = 0.12) for women with CPD compared with nondisabled women. Conclusions: Women with CPD do become pregnant, and their numbers will likely grow. Obstetrical practitioners therefore require training about the special needs of these women. C1 [Iezzoni, Lisa I.; Yu, Jun; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Smeltzer, Suzanne C.] Villanova Univ, Coll Nursing, Ctr Nursing Res, Villanova, PA 19085 USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [1R21HD068756-01A1] FX Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Grant no. 1R21HD068756-01A1). NR 24 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2013 VL 51 IS 6 BP 555 EP 562 DI 10.1097/MLR.0b013e318290218d PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 145VD UT WOS:000319045800013 PM 23604018 ER PT J AU Stewart, DS Hotta, M Desai, R Forman, SA AF Stewart, Deirdre S. Hotta, Mayo Desai, Rooma Forman, Stuart A. TI State-Dependent Etomidate Occupancy of Its Allosteric Agonist Sites Measured in a Cysteine-Substituted GABA(A) Receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID ANESTHETIC BINDING-SITE; A RECEPTORS; GENERAL-ANESTHETICS; SUBUNIT INTERFACE; AZI-ETOMIDATE; MODULATION; ACTIVATION; MUTATIONS; PROPOFOL; MODEL AB A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant g-aminobutyric acid type A (GABA(A)) receptor with unique characteristics allowing the determination of allosteric agonist site occupancy in both inactive and active receptors. Etomidate, the allosteric agonist, is an anesthetic that activates or modulates alpha 1 beta 2 gamma 2L GABA(A) receptors via transmembrane sites near beta 2M286 residues in M3 domains. Voltage-clamp electrophysiology studies of alpha 1 beta 2M286C gamma 2L receptors show that GABA is an efficacious agonist and that etomidate modulates GABA-activated activity, but direct etomidate agonism is absent. Quantitative analysis of mutant activity using an established Monod-Wyman-Changeux (MWC) allosteric model indicates that the intrinsic efficacy of etomidate, defined as its relative affinity for active versus inactive receptors, is lower than in wild-type receptors. Para-chloromercuribenzene sulfonate covalently modifies beta 2M286C side-chain sulfhydryls, irreversibly altering GABA-induced currents. Etomidate concentration dependently reduces the apparent rate of beta 2M286C-pCMBS bond formation, tracked electrophysiologically. High etomidate concentrations completely protect the beta 2M286C suflhydryl from covalent modification, suggesting close steric interactions. The 50% protective etomidate concentration (PC50) is 14 mu M in inactive receptors and 1.1 to 2.2 mu M during GABA-activation, experimentally demonstrating that activated receptors bind etomidate more avidly than do inactive receptors. The experimental PC50 values are remarkably close to, and therefore validate, MWC model predictions for etomidate dissociation constants in both inactive and active receptors. Our results support MWC models as valid frameworks for understanding the agonism, coagonism, and modulation of ligand-gated ion channels. C1 [Hotta, Mayo; Desai, Rooma; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Beecher Mallinckrodt Res Labs, Boston, MA 02114 USA. [Hotta, Mayo; Desai, Rooma; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Forman, Stuart A.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Stewart, Deirdre S.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 444,55 Fruit St, Boston, MA 02114 USA. EM saforman@partners.org FU National Institutes of Health National Institute of General Medical Sciences [GM58448, GM089745] FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grants GM58448 and GM089745]. NR 25 TC 9 Z9 9 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 2013 VL 83 IS 6 BP 1200 EP 1208 DI 10.1124/dmd.112.084558 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 146RY UT WOS:000319109700005 PM 23525330 ER PT J AU Scharf, JM Yu, D Mathews, CA Neale, BM Stewart, SE Fagerness, JA Evans, P Gamazon, E Edlund, CK Service, SK Tikhomirov, A Osiecki, L Illmann, C Pluzhnikov, A Konkashbaev, A Davis, LK Han, B Crane, J Moorjani, P Crenshaw, AT Parkin, MA Reus, VI Lowe, TL Rangel-Lugo, M Chouinard, S Dion, Y Girard, S Cath, DC Smit, JH King, RA Fernandez, TV Leckman, JF Kidd, KK Kidd, JR Pakstis, AJ State, MW Herrera, LD Romero, R Fournier, E Sandor, P Barr, CL Phan, N Gross-Tsur, V Benarroch, F Pollak, Y Budman, CL Bruun, RD Erenberg, G Naarden, AL Lee, PC Weiss, N Kremeyer, B Berrio, GB Campbell, DD Silgado, JCC Ochoa, WC Restrepo, SCM Muller, H Duarte, AVV Lyon, GJ Leppert, M Morgan, J Weiss, R Grados, MA Anderson, K Davarya, S Singer, H Walkup, J Jankovic, J Tischfield, JA Heiman, GA Gilbert, DL Hoekstra, PJ Robertson, MM Kurlan, R Liu, C Gibbs, JR Singleton, A Hardy, J Strengman, E Ophoff, RA Wagner, M Moessner, R Mirel, DB Posthuma, D Sabatti, C Eskin, E Conti, DV Knowles, JA Ruiz-Linares, A Rouleau, GA Purcell, S Heutink, P Oostra, BA McMahon, WM Freimer, NB Cox, NJ Pauls, DL AF Scharf, J. M. Yu, D. Mathews, C. A. Neale, B. M. Stewart, S. E. Fagerness, J. A. Evans, P. Gamazon, E. Edlund, C. K. Service, S. K. Tikhomirov, A. Osiecki, L. Illmann, C. Pluzhnikov, A. Konkashbaev, A. Davis, L. K. Han, B. Crane, J. Moorjani, P. Crenshaw, A. T. Parkin, M. A. Reus, V. I. Lowe, T. L. Rangel-Lugo, M. Chouinard, S. Dion, Y. Girard, S. Cath, D. C. Smit, J. H. King, R. A. Fernandez, T. V. Leckman, J. F. Kidd, K. K. Kidd, J. R. Pakstis, A. J. State, M. W. Herrera, L. D. Romero, R. Fournier, E. Sandor, P. Barr, C. L. Phan, N. Gross-Tsur, V. Benarroch, F. Pollak, Y. Budman, C. L. Bruun, R. D. Erenberg, G. Naarden, A. L. Lee, P. C. Weiss, N. Kremeyer, B. Berrio, G. B. Campbell, D. D. Cardona Silgado, J. C. Ochoa, W. C. Mesa Restrepo, S. C. Muller, H. Valencia Duarte, A. V. Lyon, G. J. Leppert, M. Morgan, J. Weiss, R. Grados, M. A. Anderson, K. Davarya, S. Singer, H. Walkup, J. Jankovic, J. Tischfield, J. A. Heiman, G. A. Gilbert, D. L. Hoekstra, P. J. Robertson, M. M. Kurlan, R. Liu, C. Gibbs, J. R. Singleton, A. Hardy, J. Strengman, E. Ophoff, R. A. Wagner, M. Moessner, R. Mirel, D. B. Posthuma, D. Sabatti, C. Eskin, E. Conti, D. V. Knowles, J. A. Ruiz-Linares, A. Rouleau, G. A. Purcell, S. Heutink, P. Oostra, B. A. McMahon, W. M. Freimer, N. B. Cox, N. J. Pauls, D. L. CA North Amer Brain Expression UK Human Brain Expression Database TI Genome-wide association study of Tourette's syndrome SO MOLECULAR PSYCHIATRY LA English DT Article DE genetics; GWAS; neurodevelopmental disorder; tics; Tourette's syndrome ID COPY NUMBER VARIANTS; COMMON VARIANTS; SLITRK1 VAR321; SCHIZOPHRENIA; FAMILY; INDIVIDUALS; DEPENDENCE; MUTATIONS; DISORDER; POLR3B AB Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P < 5 x 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P = 1.85 x 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal ( P = 3.6 x 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. C1 [Scharf, J. M.; Yu, D.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Osiecki, L.; Illmann, C.; Crane, J.; Purcell, S.; Pauls, D. L.] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Scharf, J. M.; Yu, D.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Osiecki, L.; Illmann, C.; Crane, J.; Purcell, S.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Movement Disorders Unit, Boston, MA 02114 USA. [Scharf, J. M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Scharf, J. M.; Neale, B. M.; Purcell, S.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Mathews, C. A.; Reus, V. I.; Lowe, T. L.; Rangel-Lugo, M.; Lee, P. C.; Weiss, N.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neale, B. M.; Moorjani, P.; Crenshaw, A. T.; Parkin, M. A.; Mirel, D. B.; Purcell, S.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Neale, B. M.; Purcell, S.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Stewart, S. E.] Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada. [Evans, P.; Gamazon, E.; Tikhomirov, A.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Cox, N. J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Evans, P.; Gamazon, E.; Tikhomirov, A.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Cox, N. J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Edlund, C. K.; Conti, D. V.] Univ So Calif, Dept Prevent Med, Div Biostat, Los Angeles, CA 90089 USA. [Edlund, C. K.] Univ So Calif, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA. [Service, S. K.; Strengman, E.; Ophoff, R. A.; Freimer, N. B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA USA. [Han, B.; Eskin, E.] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA. [Moorjani, P.] Harvard Univ, Dept Genet, Cambridge, MA 02138 USA. [Chouinard, S.; Dion, Y.; Girard, S.; Rouleau, G. A.] Univ Montreal, Montreal, PQ, Canada. [Cath, D. C.; Smit, J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Cath, D. C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [King, R. A.; Fernandez, T. V.; Leckman, J. F.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Kidd, K. K.; Kidd, J. R.; Pakstis, A. J.; State, M. W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Herrera, L. D.; Romero, R.; Fournier, E.] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Sandor, P.; Barr, C. L.; Phan, N.] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. [Sandor, P.] Univ Toronto, Dept Psychiat, Div Child Psychiat, Toronto, ON, Canada. [Barr, C. L.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Gross-Tsur, V.; Pollak, Y.] Shaare Zedek Med Ctr, Neuropediat Unit, Jerusalem, Israel. [Benarroch, F.] Hadassah Hebrew Univ, Med Ctr, Herman Dana Div Child & Adolescent Psychiat, Jerusalem, Israel. [Budman, C. L.; Bruun, R. D.] North Shore Long Isl Jewish Med Ctr, Manhasset, NY USA. [Budman, C. L.] Hofstra Univ, Sch Med, Hempstead, NY 11550 USA. [Bruun, R. D.] NYU, Med Ctr, New York, NY 10016 USA. [Erenberg, G.] Cleveland Clin, Cleveland, OH 44106 USA. [Naarden, A. L.] Med City Dallas Hosp, Dept Clin Res, Dallas, TX USA. [Kremeyer, B.; Campbell, D. D.; Muller, H.; Robertson, M. M.; Hardy, J.; Ruiz-Linares, A.] UCL, London, England. [Kremeyer, B.] Wellcome Trust Sanger Inst, Cambridge, England. [Berrio, G. B.; Cardona Silgado, J. C.; Ochoa, W. C.; Mesa Restrepo, S. C.; Valencia Duarte, A. V.] Univ Antioquia, Medellin, Colombia. [Campbell, D. D.] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Campbell, D. D.] Univ Hong Kong, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China. [Valencia Duarte, A. V.] Univ Pontificia Bolivariana, Medellin, Colombia. [Lyon, G. J.; Leppert, M.; Morgan, J.; Weiss, R.; McMahon, W. M.] Univ Utah, Salt Lake City, UT USA. [Lyon, G. J.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 11724 USA. [Grados, M. A.; Anderson, K.; Davarya, S.; Singer, H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Walkup, J.] Weill Cornell Med Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, New York, NY USA. [Jankovic, J.] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, J.] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. [Tischfield, J. A.; Heiman, G. A.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Tischfield, J. A.; Heiman, G. A.] Rutgers State Univ, Human Genet Inst New Jersey, Piscataway, NJ USA. [Gilbert, D. L.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Gilbert, D. L.] Univ Cincinnati, Cincinnati, OH USA. [Hoekstra, P. J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Robertson, M. M.] St Georges Hosp & Med Sch, London, England. [Kurlan, R.] Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA. [Liu, C.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Gibbs, J. R.; Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Strengman, E.; Ophoff, R. A.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Wagner, M.; Moessner, R.] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Posthuma, D.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands. [Posthuma, D.; Heutink, P.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands. [Posthuma, D.] Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands. [Sabatti, C.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Eskin, E.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Knowles, J. A.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Purcell, S.] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA. [Oostra, B. A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. RP Pauls, DL (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. EM jscharf@partners.org; dpauls@pngu.mgh.harvard.edu RI Hoekstra, Pieter/O-4396-2014; reus, victor/I-7923-2015; Gilbert, Donald/D-6443-2016; Wagner, Michael/E-2325-2011; Trabzuni, Daniah/C-4034-2012; Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; Lyon, Gholson/D-2765-2014; Singleton, Andrew/C-3010-2009; Weale, Michael/F-2587-2010; Stewart, Evelyn/K-6961-2014 OI Fernandez, Thomas V/0000-0003-0830-022X; Tischfield, Jay/0000-0003-3217-8287; Gamazon, Eric/0000-0003-4204-8734; Stewart, S. Evelyn/0000-0002-0994-6383; reus, victor/0000-0002-8193-5697; Gilbert, Donald/0000-0002-9245-6878; Wagner, Michael/0000-0003-2589-6440; Trabzuni, Daniah/0000-0003-4826-9570; Campbell, Desmond/0000-0003-1085-714X; Barr, Cathy/0000-0003-0361-0106; Lyon, Gholson/0000-0002-5869-0716; Weale, Michael/0000-0003-4593-1186; FU NIH; Tourette Syndrome Association (TSA); Psyadon; Shire; Solway; UCB Pharma; Janssen; Eli Lilly; Pfizer; Prestwick; Psyadon Pharmaceuticals; Otsuka Pharmaceuticals; NINDS; TSA; Talecris Biotherapeutics; Klingenstein Third Generation Foundation; John Wiley and Sons; McGraw Hill; Oxford University Press; Allergan; Allon Therapeutics; Ceregene; Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation; EMD Serono; Huntington's Disease Society of America; Huntington Study Group; Impax Pharmaceuticals; Ipsen Limited; Lundbeck; Medtronic; Merz Pharmaceuticals; Michael J Fox Foundation for Parkinson Research; National Institutes of Health; National Parkinson Foundation; Neurogen; St Jude Medical; Teva Pharmaceutical Industries; University of Rochester; Parkinson Study Group; Tourette Syndrome Association; Judah Foundation; NIH [NS40024, NS16648, NS037484, NS043538, MH079489, MH085057]; Tourette Syndrome Association International Consortium for Genetics; American Recovery and Re-investment Act (ARRA) [NS40024-07S1, NS16648-29S1]; American Academy of Neurology Foundation Grant; National Center for Research Resources [U54 RR020278]; New Jersey Center for Tourette Syndrome & Associated Disorders (through New Jersey Department of Health and Senior Services) [08-1827-FS-N-0, P01MH049351, R01MH061940, K05MH076273, T32MH018268]; UK Medical Research Council; Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services project [Z01 AG000932-02]; NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH contract [HHSN268200782096C]; NIMH; Guilford Press; Oxford Press FX Drs Pauls, Scharf, Mathews, Cox, Freimer, McMahon, Heutink, Oostra, Grados, King, Rouleau, Sandor and Budman have all received research support from the NIH and the Tourette Syndrome Association (TSA) on behalf of the TSA International Consortium for Genetics (TSAICG). Drs Scharf, Mathews and Grados have received honoraria and travel support from the TSA. Dr Mathews is a member of the TSA Medical Advisory Board. Dr Sandor has received support and consulting fees from Psyadon, Shire, Solway, UCB Pharma, Janssen, Eli Lilly, Pfizer and Prestwick. Dr Budman has been funded by Psyadon Pharmaceuticals, Otsuka Pharmaceuticals and NINDS and is a member of the National TSA Medical Advisory Board, LI TSA and LI CHADD Medical Advisory Boards. Dr Hoekstra has received honoraria for advice through Desitin, Eli Lilly and Shire. Dr Dion has received honoraria from Biovail Pharma, Pfizer and Eli Lilly. Dr Leckman has been funded by the NIH, the TSA, Talecris Biotherapeutics, Klingenstein Third Generation Foundation, John Wiley and Sons, McGraw Hill and Oxford University Press. Dr Walkup receives research support, travel support for paid and unpaid activities, serves in an unpaid position on the Medical Advisory Board and receives an honorarium for an Educational Meeting from the TSA. He receives royalties from Guilford Press and Oxford Press. He received free medication and placebo from Lilly, Pfizer and Abbott for NIH-funded studies. Dr Jankovic has received research grants from the following: Allergan, Allon Therapeutics, Ceregene, Chelsea Therapeutics, Diana Helis Henry Medical Research Foundation, EMD Serono, Huntington's Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck, Medtronic, Merz Pharmaceuticals, Michael J Fox Foundation for Parkinson Research, National Institutes of Health, National Parkinson Foundation, Neurogen, St Jude Medical, Teva Pharmaceutical Industries, University of Rochester and Parkinson Study Group. He has served as a consultant or advisory committee member for Allergan, Chelsea Therapeutics, EMD Serono, Lundbeck, Merz Pharmaceuticals, Michael J Fox Foundation for Parkinson Research and Teva Pharmaceutical Industries. He also serves on the editorial boards for Elsevier, Medlink: Neurology, Neurology in Clinical Practice, Neurotoxin Institute, Scientiae and UpToDate. Dr Knowles is on the Scientific Advisory Committee for Next-Generation Sequencing of Life Technologies, and is a technical advisor to SoftGenetics. Ms Anderson, Dr Barr, Dr Benarroch, Mr Berrio, Dr Bruun, Mr Campbell, Dr Cath, Dr Chouinard, Dr Conti, Ms Crane, Mr Crenshaw, Ms Davarya, Dr Davis, Ms Duarte, Mr Edlund, Dr Erenberg, Dr Eskin, Dr Evans, Mr Fagerness, Dr Fernandez, Mr Fournier, Mr Gamazon, Mr Gibbs, Dr Gilbert, Dr Girard, Dr Gross-Tsur, Dr Han, Dr Hardy, Dr Heiman, Dr Herrera, Dr Heutink, Dr Illmann, Dr J Kidd, Dr K Kidd, Mr. Konkashbaev, Dr Kremeyer, Dr Kurlan, Dr Lee, Dr Leppert, Dr Liu, Dr Lowe, Dr Lyon, Dr Mirel, Dr Moessner, Ms Moorjani, Mr Morgan, Mr Muller, Dr Naarden, Dr Neale, Dr Ochoa, Dr Ophoff, Ms Osiecki, Dr Pakstis, Ms Parkin, Mr Phan, Dr Pluzhnikov, Dr Pollak, Dr Posthuma, Dr Purcell, Dr Rangel-Lugo, Dr Restrepo, Dr Reus, Ms Rivas, Dr Robertson, Ms Romero, Dr Ruiz-Linares, Dr Sabatti, Ms Service, Mr Silgado, Dr Singer, Dr Singleton, Dr Smit, Dr State, Dr Stewart, Mr. Strengman, Dr Tikhomirov, Dr Tischfield, Dr Wagner, Dr N Weiss, Dr R Weiss and Ms Yu declare no conflict of interest.; We are grateful to all the patients with Tourette's syndrome who generously agreed to participate in this study. Furthermore, the members of the Tourette Syndrome Association International Consortium for Genetics are deeply indebted to the Tourette Syndrome Association for their guidance and support. We also thank Libby Bernier and Janelle Alabiso for their assistance in manuscript preparation and Stephan Ripke for help with meta-analysis figures. This work was supported by a grant from the Judah Foundation, NIH Grants NS40024 to DLP and the Tourette Syndrome Association International Consortium for Genetics, NIH Grant NS16648 and a grant from the Tourette Syndrome Association to DLP, NIH Grant NS037484 to NBF, NIH Grant NS043538 to AR-L, American Recovery and Re-investment Act (ARRA) awards NS40024-07S1 and NS16648-29S1 to DLP, NIH Grant MH079489, and an American Academy of Neurology Foundation Grant and NIH Grant MH085057 to JMS. The Broad Institute Center for Genotyping and Analysis was supported by Grant U54 RR020278 from the National Center for Research Resources. Support was also provided by the New Jersey Center for Tourette Syndrome & Associated Disorders (through New Jersey Department of Health and Senior Services: 08-1827-FS-N-0) to GAH and JAT and P01MH049351, R01MH061940, K05MH076273 and T32MH018268 to JFL. Funding support for generation of the eQTL data was provided by the UK Medical Research Council and the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services project Z01 AG000932-02. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). The data sets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0 00092.v1.p1 through dbGaP accession number phs000092.v1.p. None of the funding agencies for this project (NINDS, NIMH, the Tourette Syndrome Association and the Judah Foundation) had any influence or played any role in (1) the design or conduct of the study; (2) management, analysis or interpretation of the data; and (3) preparation, review or approval of the manuscript. NR 55 TC 56 Z9 56 U1 3 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2013 VL 18 IS 6 BP 721 EP 728 DI 10.1038/mp.2012.69 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 151HP UT WOS:000319451600015 PM 22889924 ER PT J AU Hett, EC Slater, LH Mark, KG Kawate, T Monks, BG Stutz, A Latz, E Hung, DT AF Hett, Erik C. Slater, Louise H. Mark, Kevin G. Kawate, Tomohiko Monks, Brian G. Stutz, Andrea Latz, Eicke Hung, Deborah T. TI Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis SO NATURE CHEMICAL BIOLOGY LA English DT Article ID ANTHRAX LETHAL TOXIN; NF-KAPPA-B; INFLAMMASOME ACTIVATION; MACROPHAGE APOPTOSIS; MURINE MACROPHAGES; NLRP3 EXPRESSION; IKK COMPLEX; PKR; MAP; SUSCEPTIBILITY AB Formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. Pyroptotic cell death induced by anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1 activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in a phenotypic screen as a small molecule that protects macrophages from LT-induced death. Using chemical proteomics, we identified protein kinase R (PKR) as the target of 7DG and show that RNAi knockdown of PKR phenocopies treatment with 7DG. Further, we show that PKR's role in ASC assembly and caspase-1 activation induced by several different inflammasome stimuli is independent of PKR's kinase activity, demonstrating that PKR has a previously uncharacterized role in caspase-1 activation and pyroptosis that is distinct from its reported kinase-dependent roles in apoptosis and inflammasome formation in lipopolysaccharide-primed cells. Remarkably, PKR has different roles in two distinct cell death pathways and has a broad role in inflammasome function relevant in other diseases. C1 [Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Monks, Brian G.; Latz, Eicke] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA USA. [Monks, Brian G.; Stutz, Andrea; Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany. [Latz, Eicke] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. RP Hett, EC (reprint author), Pfizer, Worldwide Med Chem, Chem Biol Grp, Cambridge, MA USA. EM hett@molbio.mgh.harvard.edu; hung@molbio.mgh.harvard.edu RI Monks, Brian/B-8362-2015; Latz, Eicke/H-3951-2014 OI Monks, Brian/0000-0003-4008-3093; Latz, Eicke/0000-0003-1488-5666 FU US National Institutes of Health (NIH) National Research Service Award fellowship [F32AI084323]; NIH [U54 AI057159] FX E.C.H. was funded by an US National Institutes of Health (NIH) National Research Service Award fellowship F32AI084323. This work was supported in part by NIH U54 AI057159 to D.T.H.). NR 45 TC 29 Z9 29 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JUN PY 2013 VL 9 IS 6 BP 398 EP + DI 10.1038/NCHEMBIO.1236 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 149NS UT WOS:000319328200012 PM 23603659 ER PT J AU Sokolovska, A Becker, CE Ip, WKE Rathinam, VAK Brudner, M Paquette, N Tanne, A Vanaja, SK Moore, KJ Fitzgerald, KA Lacy-Hulbert, A Stuart, LM AF Sokolovska, Anna Becker, Christine E. Ip, W. K. Eddie Rathinam, Vijay A. K. Brudner, Matthew Paquette, Nicholas Tanne, Antoine Vanaja, Sivapriya K. Moore, Kathryn J. Fitzgerald, Katherine A. Lacy-Hulbert, Adam Stuart, Lynda M. TI Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function SO NATURE IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR; INNATE IMMUNE-SYSTEM; H+-ATPASE ACTIVITY; PROTEOLYTIC CLEAVAGE; STAPHYLOCOCCUS-AUREUS; NALP3 INFLAMMASOME; BACTERIAL LIGANDS; DENDRITIC CELLS; MATURATION; ACIDIFICATION AB Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates many functions of these organelles that allow phagosomes to participate in processes that are essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3 inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3 inflammasome and caspase-1 in host defense. C1 [Sokolovska, Anna; Becker, Christine E.; Ip, W. K. Eddie; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Lacy-Hulbert, Adam; Stuart, Lynda M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sokolovska, Anna; Becker, Christine E.; Ip, W. K. Eddie; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Lacy-Hulbert, Adam; Stuart, Lynda M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sokolovska, Anna; Becker, Christine E.; Ip, W. K. Eddie; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Lacy-Hulbert, Adam; Stuart, Lynda M.] Harvard Univ, Sch Med, Boston, MA USA. [Rathinam, Vijay A. K.; Vanaja, Sivapriya K.; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA. [Moore, Kathryn J.] NYU, Med Ctr, Dept Med, New York, NY 10016 USA. [Moore, Kathryn J.] NYU, Med Ctr, Dept Cell Biol, New York, NY 10016 USA. [Stuart, Lynda M.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Stuart, LM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM asokolovska@partners.org; lstuart@partners.org OI Lacy-Hulbert, Adam/0000-0003-2162-0156; Moore, kathryn/0000-0003-2505-2547 FU US National Institutes of Health; National Institute of Allergy and Infectious Diseases [RO1 AI079198, RO1 AI093752]; National Institutes of Health National Institute on Aging [RO1 AG020255]; Crohns' and Colitis and Hood foundations; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [RO1 DK093695]; Massachusetts General Hospital Executive Committee on Research; New England Regional Center of Excellence-Biodefense and Emerging Infectious Diseases [U54 AI057159] FX This work was funded by grants from US National Institutes of Health National Institute of Allergy and Infectious Diseases to L.M.S. (RO1 AI079198) and K.A.F. (RO1 AI093752), National Institutes of Health National Institute on Aging to K.J.M. (RO1 AG020255), grants from the Crohns' and Colitis and Hood foundations and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases to A.L.-H. (RO1 DK093695), and postdoctoral fellowships from Massachusetts General Hospital Executive Committee on Research to A.S. and New England Regional Center of Excellence-Biodefense and Emerging Infectious Diseases (U54 AI057159 to N.P.). Electron microscopy was performed by M. McKee in the Microscopy Core of the Center for Systems Biology. NR 55 TC 57 Z9 59 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2013 VL 14 IS 6 BP 543 EP + DI 10.1038/ni.2595 PG 13 WC Immunology SC Immunology GA 146RG UT WOS:000319107600007 PM 23644505 ER PT J AU Mingueneau, M Kreslavsky, T Gray, D Heng, T Cruse, R Ericson, J Bendall, S Spitzer, M Nolan, G Kobayashi, K von Boehmer, H Mathis, D Benoist, C Best, AJ Knell, J Goldrath, A Jojic, V Koller, D Shay, T Regev, A Cohen, N Brennan, P Brenner, M Kim, F Rao, TN Wagers, A Heng, T Ericson, J Rothamel, K Ortiz-Lopez, A Mathis, D Bezman, NA Sun, JC Min-Oo, G Kim, CC Lanier, LL Miller, J Brown, B Merad, M Gautier, EL Jakubzick, C Randolph, GJ Monach, P Blair, DA Dustin, ML Shinton, SA Hardy, RR Laidlaw, D Collins, J Gazit, R Rossi, DJ Malhotra, N Sylvia, K Kang, J Kreslavsky, T Fletcher, A Elpek, K Bellemare-Pelletier, A Malhotra, D Turley, S AF Mingueneau, Michael Kreslavsky, Taras Gray, Daniel Heng, Tracy Cruse, Richard Ericson, Jeffrey Bendall, Sean Spitzer, Matt Nolan, Garry Kobayashi, Koichi von Boehmer, Harald Mathis, Diane Benoist, Christophe Best, Adam J. Knell, Jamie Goldrath, Ananda Jojic, Vladimir Koller, Daphne Shay, Tal Regev, Aviv Cohen, Nadia Brennan, Patrick Brenner, Michael Kim, Francis Rao, Tata Nageswara Wagers, Amy Heng, Tracy Ericson, Jeffrey Rothamel, Katherine Ortiz-Lopez, Adriana Mathis, Diane Bezman, Natalie A. Sun, Joseph C. Min-Oo, Gundula Kim, Charlie C. Lanier, Lewis L. Miller, Jennifer Brown, Brian Merad, Miriam Gautier, Emmanuel L. Jakubzick, Claudia Randolph, Gwendalyn J. Monach, Paul Blair, David A. Dustin, Michael L. Shinton, Susan A. Hardy, Richard R. Laidlaw, David Collins, Jim Gazit, Roi Rossi, Derrick J. Malhotra, Nidhi Sylvia, Katelyn Kang, Joonsoo Kreslavsky, Taras Fletcher, Anne Elpek, Kutlu Bellemare-Pelletier, Angelique Malhotra, Deepali Turley, Shannon CA Immunological Genome Consortium TI The transcriptional landscape of alpha beta T cell differentiation SO NATURE IMMUNOLOGY LA English DT Article ID SELECTION IN-VIVO; GENE-EXPRESSION ANALYSIS; NEGATIVE SELECTION; POSITIVE SELECTION; PRE-TCR; C-MYC; CLONAL DELETION; LYMPHOCYTE DEVELOPMENT; INDUCED PROLIFERATION; THYMOCYTE SELECTION AB The differentiation of abT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation. C1 [Mingueneau, Michael; Cruse, Richard; Ericson, Jeffrey; Mathis, Diane; Benoist, Christophe; Heng, Tracy; Ericson, Jeffrey; Rothamel, Katherine; Ortiz-Lopez, Adriana; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA. [Kreslavsky, Taras; Kobayashi, Koichi; von Boehmer, Harald; Kreslavsky, Taras; Fletcher, Anne; Elpek, Kutlu; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Turley, Shannon] Dana Farber Canc Inst, Boston, MA USA. [Gray, Daniel] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia. [Gray, Daniel] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Mol Genet Canc Div, Parkville, Vic 3050, Australia. [Gray, Daniel] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3050, Australia. [Heng, Tracy] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia. [Bendall, Sean; Spitzer, Matt; Nolan, Garry] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Palo Alto, CA 94304 USA. [Kobayashi, Koichi] Texas A&M Hlth Sci Ctr, Dept Microbial & Mol Pathogenesis, College Stn, TX USA. [Best, Adam J.; Knell, Jamie; Goldrath, Ananda] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [Jojic, Vladimir; Koller, Daphne] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Shay, Tal; Regev, Aviv] MIT, Broad Inst, Cambridge, MA 02139 USA. [Shay, Tal; Regev, Aviv] MIT, Dept Biol, Cambridge, MA USA. [Cohen, Nadia; Brennan, Patrick; Brenner, Michael] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Kim, Francis; Rao, Tata Nageswara; Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bezman, Natalie A.; Sun, Joseph C.; Min-Oo, Gundula; Kim, Charlie C.; Lanier, Lewis L.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Miller, Jennifer; Brown, Brian; Merad, Miriam; Gautier, Emmanuel L.; Jakubzick, Claudia; Randolph, Gwendalyn J.] Mt Sinai Hosp, Icahn Med Inst, New York, NY 10029 USA. [Gautier, Emmanuel L.; Randolph, Gwendalyn J.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Monach, Paul] Boston Univ, Dept Med, Boston, MA 02215 USA. [Blair, David A.; Dustin, Michael L.] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA. [Shinton, Susan A.; Hardy, Richard R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Laidlaw, David] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. [Collins, Jim] Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Boston, MA 02215 USA. [Gazit, Roi; Rossi, Derrick J.] Childrens Hosp, Program Mol Med, Boston, MA 02115 USA. [Malhotra, Nidhi; Sylvia, Katelyn; Kang, Joonsoo] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Kreslavsky, Taras; Fletcher, Anne; Elpek, Kutlu; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Turley, Shannon] Harvard Univ, Sch Med, Boston, MA USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu; cbdm@hms.harvard.edu RI Gray, Daniel/A-3293-2013; Gautier, Emmanuel L./E-2259-2017; OI Gray, Daniel/0000-0002-8457-8242; Gautier, Emmanuel L./0000-0003-2976-7566; Malhotra, Deepali/0000-0002-8215-7639; Dustin, Michael/0000-0003-4983-6389; Miller, Jennifer/0000-0002-3591-369X FU US National Institutes of Health [AI072073]; Human Frontier Science Program [HFSP-LT000096]; National Health and Medical Research Council [637353]; Australian Research Council [LP110201169] FX We thank K. Hattori, A. Ortiz-Lopez and N. Asinovski for technical assistance with mice and antibodies; J. Moore and A. Kressler for flow cytometry; and C. Laplace for assistance with figure preparation. Supported by the US National Institutes of Health (AI072073), the Human Frontier Science Program (HFSP-LT000096 to M. M.), the National Health and Medical Research Council (637353 to D.G.) and the Australian Research Council (LP110201169 to, T.H.). NR 92 TC 71 Z9 71 U1 0 U2 41 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2013 VL 14 IS 6 BP 619 EP + DI 10.1038/ni.2590 PG 16 WC Immunology SC Immunology GA 146RG UT WOS:000319107600015 PM 23644507 ER PT J AU Kargi, AY Merriam, GR AF Kargi, Atil Y. Merriam, George R. TI Diagnosis and treatment of growth hormone deficiency in adults SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Article ID QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; GH REPLACEMENT THERAPY; BONE-MINERAL DENSITY; INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK MARKERS; PLACEBO-CONTROLLED TRIAL; INSULIN TOLERANCE-TEST; LONG-TERM MORTALITY; BODY-MASS INDEX AB The availability of synthetic recombinant human growth hormone (GH) in potentially unlimited quantities since the 1980s has improved understanding of the many nonstatural effects of GH on metabolism, body composition, physical and psychological function, as well as the consequences of GH deficiency in adult life. Adult GH deficiency is now recognized as a distinct if nonspecific syndrome with considerable adverse health consequences. GH replacement therapy in lower doses than those used in children can reverse many of these abnormalities and restore functional capacities toward or even to normal; if dosed appropriately, GH therapy has few adverse effects. Although some doubts remain about possible long-term risks of childhood GH therapy, most registries of adult GH replacement therapy, albeit limited in study size and duration, have not shown an increased incidence of cancers or of cardiovascular morbidity or mortality. C1 [Kargi, Atil Y.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA. [Merriam, George R.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Merriam, George R.] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Merriam, GR (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Box 356426, Seattle, WA 98195 USA. EM merriam@uw.edu FU National Institute of Aging, US National Institutes of Health FX The authors thank P. Asberry, S. Brickle, M. Kletke and L. Smith for their assistance with the work of the research group. The authors gratefully acknowledge research support from the National Institute of Aging, US National Institutes of Health, and from the facilities and resources of the US Department of Veterans Affairs Puget Sound Health Care System. NR 136 TC 12 Z9 13 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD JUN PY 2013 VL 9 IS 6 BP 335 EP 345 DI 10.1038/nrendo.2013.77 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149QK UT WOS:000319335900007 PM 23629539 ER PT J AU Cahan, P Daley, GQ AF Cahan, Patrick Daley, George Q. TI Origins and implications of pluripotent stem cell variability and heterogeneity SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID GENE-EXPRESSION SIGNATURES; TRANSCRIPTIONAL REGULATORY CIRCUITRY; HUMAN SOMATIC-CELLS; MOUSE ES CELLS; SELF-RENEWAL; COPY NUMBER; REGENERATIVE MEDICINE; MOLECULAR SIGNATURE; IPS CELLS; DIFFERENTIATION PROPENSITY AB Pluripotent stem cells constitute a platform to model disease and developmental processes and can potentially be used in regenerative medicine. However, not all pluripotent cell lines are equal in their capacity to differentiate into desired cell types in vitro. Genetic and epigenetic variations contribute to functional variability between cell lines and heterogeneity within clones. These genetic and epigenetic variations could 'lock' the pluripotency network resulting in residual pluripotent cells or alter the signalling response of developmental pathways leading to lineage bias. The molecular contributors to functional variability and heterogeneity in both embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are only beginning to emerge, yet they are crucial to the future of the stem cell field. C1 [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol & Oncol,Manton Ctr Orphan Dis, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Harvard Stem Cell Inst, Dept Biol Chem & Mol Pharmacol,Med Sch, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol & Oncol,Manton Ctr Orphan Dis, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Cahan, Patrick/0000-0003-3652-2540 FU US National Institutes of Health (NIH) [UO 1-HL100001, R24-DK092760, P50HG005550, RC2-HL102815, RC4DK 090913]; Roche Foundation for Anemia Research; Alex's Lemonade Stand Foundation; Doris Duke Charitable Foundation; Ellison Medical Foundation; National Heart, Lung, and Blood Institute (NHLBI) [T32HL007623, 2T32HL66987-11] FX G.Q.D. is supported by grants from the US National Institutes of Health (NIH) (UO 1-HL100001 Progenitor cell biology consortium, R24-DK092760, P50HG005550 and special funds from the ARRA stimulus package- RC2-HL102815, RC4DK 090913), the Roche Foundation for Anemia Research, Alex's Lemonade Stand Foundation, Doris Duke Charitable Foundation and the Ellison Medical Foundation. G.Q.D. is an affiliate member of the Broad Institute and an investigator of the Manton Center for Orphan Disease Research and the Howard Hughes Medical Institute. P.C. is supported by grants T32HL007623 and 2T32HL66987-11 from the National Heart, Lung, and Blood Institute (NHLBI). The authors would like to thank R. Zhao and A. De Los Angeles for helpful discussions. NR 116 TC 92 Z9 93 U1 5 U2 88 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JUN PY 2013 VL 14 IS 6 BP 357 EP 368 DI 10.1038/nrm3584 PG 12 WC Cell Biology SC Cell Biology GA 151LO UT WOS:000319462200012 PM 23673969 ER PT J AU Kilbride, RD Reynolds, AS Szaflarski, JP Hirsch, LJ AF Kilbride, R. D. Reynolds, A. S. Szaflarski, J. P. Hirsch, L. J. TI Clinical Outcomes Following Prolonged Refractory Status Epilepticus (PRSE) SO NEUROCRITICAL CARE LA English DT Article DE Status epilepticus; PRSE; Neuro ICU; Outcomes ID COMA AB To define the clinical profile and outcome of patients in prolonged refractory status epilepticus (PRSE), and investigate possible predictors of outcome. We reviewed 63 consecutive patients with PRSE cared for in the medical and neurointensive care units of three academic medical centers over a 9-year period. For this multi-center retrospective cohort study, PRSE was defined as SE that persisted despite at least 1 week of induced coma. Variables examined for their relationship to outcome included etiology, EEG, neuroimaging, and age. Forty-two (66 %) of 63 patients in PRSE survived to discharge from hospitalization. Fourteen (22 %) patients had a good outcome (mRS a parts per thousand currency sign 3) at last available follow up (at least 6 months post-PRSE). Of these, 6 (10 %) individuals had no significant disability and were able to carry out all usual activities (mRS = 1). Normal neuroimaging and a reactive EEG at onset of PRSE were associated with good outcome. Good or excellent clinical outcomes were possible in patients in PRSE for up to 79 days, and in patients up to 69 years old. Good outcome is not unusual in PRSE, including in some older patients, in a variety of diagnoses, and despite months of coma. C1 [Kilbride, R. D.] Massachusetts Gen Hosp, Div Epilepsy, Boston, MA 02114 USA. [Reynolds, A. S.] Neurol Inst, Comprehens Epilepsy Ctr, New York, NY 10032 USA. [Szaflarski, J. P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Hirsch, L. J.] Yale Univ, Sch Med, Comprehens Epilepsy Ctr, Div Epilepsy & EEG,Crit Care EEG Program, New Haven, CT 06510 USA. RP Kilbride, RD (reprint author), Massachusetts Gen Hosp, Div Epilepsy, 55 Fruit St, Boston, MA 02114 USA. EM rkilbride@partners.org OI Reynolds, Alexandra/0000-0002-6364-6250 FU American Epilepsy Society FX This study was conducted on behalf of the Critical Care EEG Monitoring Research Consortium. The Critical Care EEG Monitoring Research Consortium receives support from the American Epilepsy Society. NR 12 TC 13 Z9 15 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2013 VL 18 IS 3 BP 374 EP 385 DI 10.1007/s12028-013-9823-4 PG 12 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 147II UT WOS:000319159600013 PM 23479069 ER PT J AU Schorge, JO AF Schorge, John O. TI Nonsurgical Treatment of Endometrial Hyperplasia Is the Road Less Traveled the One We Should be Taking More? SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID CANCER; ADENOCARCINOMA; HYSTERECTOMY; PROGESTIN; OUTCOMES C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. EM jschorge@partners.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2013 VL 121 IS 6 BP 1155 EP 1157 DI 10.1097/AOG.0b013e3182951846 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 151BR UT WOS:000319436100002 PM 23812445 ER PT J AU Orrell, C Levison, J Ciaranello, A Bekker, LG Kuritzkes, DR Freedberg, KA Wood, R AF Orrell, Catherine Levison, Julie Ciaranello, Andrea Bekker, Linda-Gail Kuritzkes, Daniel R. Freedberg, Kenneth A. Wood, Robin TI Resistance in Pediatric Patients Experiencing Virologic Failure With First-line and Second-line Antiretroviral Therapy SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pediatric; antiretroviral therapy; genotype; resource-limited setting; virologic failure; resistance ID DRUG-RESISTANCE; CHILDREN AB We examined HIV-1 resistance in children failing first-line and second-line antiretroviral therapy in South Africa, all with clade C virus. Those exposed to full-dose ritonavir had multiple protease resistance mutations. Nineteen percent had wild-type virus. Appropriate antiretroviral therapy sequencing in sub-Saharan African children is essential for prolong treatment options. C1 [Orrell, Catherine; Bekker, Linda-Gail; Wood, Robin] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Levison, Julie; Ciaranello, Andrea; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Levison, Julie; Ciaranello, Andrea; Kuritzkes, Daniel R.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Levison, Julie; Ciaranello, Andrea; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Levison, Julie; Kuritzkes, Daniel R.; Freedberg, Kenneth A.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Orrell, C (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, Anzio Rd, ZA-7925 Cape Town, South Africa. EM catherine.orrell@hiv-research.org.za OI Orrell, Catherine/0000-0003-1134-7475 FU ARRA PEPFAR [R01 AI085736, K01 AI078754]; IMPAACT network (NIAID); IMPAACT network (National Institute of Child Health and Human Development); AIDS Clinical Trials Group (National Institutes of Health) [UM1 AI068636] FX This work was completed through support from an ARRA PEPFAR supplement to National Institute of Allergy and Infectious Diseases (NIAID) R01 AI085736 to K.A.F., K01 AI078754 and IMPAACT network (NIAID and National Institute of Child Health and Human Development) to A.L.C. and by a Virology Specialty Laboratory subcontract from the AIDS Clinical Trials Group (National Institutes of Health grant UM1 AI068636) to D.R.K. The authors have no other funding or conflicts of interest to disclose. NR 10 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 2013 VL 32 IS 6 BP 644 EP 647 DI 10.1097/INF.0b013e3182829092 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 147ZR UT WOS:000319211700018 PM 23303240 ER PT J AU Yuen, KCJ Biller, BMK Katznelson, L Rhoads, SA Gurel, MH Chu, O Corazzini, V Spiller, K Gordon, MB Salvatori, R Cook, DM AF Yuen, Kevin C. J. Biller, Beverly M. K. Katznelson, Laurence Rhoads, Sharon A. Gurel, Michelle H. Chu, Olivia Corazzini, Valentina Spiller, Kellie Gordon, Murray B. Salvatori, Roberto Cook, David M. TI Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults SO PITUITARY LA English DT Article DE Glucagon stimulation test; Growth hormone; Growth hormone deficiency; Central adrenal insufficiency; Cortisol ID GH DEFICIENCY; (GH)-RELEASING HORMONE; ENDOCRINE-SOCIETY; DIAGNOSIS; ACTH; ARGININE; RELEASE; TIME; MEN AB Weight-based (WB: 0.03 mg/kg) and fixed dose (FD: 1-1.5 mg) regimens of the glucagon stimulation test (GST) have been used to evaluate GH and cortisol secretion in children and adults, respectively. However, experience of the WB regimen in assessing GH and cortisol secretion in adults are limited. We describe a multicenter experience using WB and FD regimens in evaluating GH and cortisol secretion in adults suspected of GH deficiency and central adrenal insufficiency. Retrospective case series of GSTs (n = 515) performed at five tertiary centers. Peak and nadir glucose, and peak GH and peak cortisol responses occurred later with WB (mean dose: 2.77 mg) compared to FD (mean dose: 1.20 mg) regimens. Main side-effects were nausea and vomiting, particularly in younger females. Nausea was comparable but vomiting was more frequent in the WB regimen (WB: 10.0 % vs FD: 2.4 %; P < 0.05). Peak and nadir glucose, Delta GH, and peak and Delta cortisol were higher in the WB regimen. In both regimens, age correlated negatively with peak cortisol levels, and body mass index (BMI), fasting, peak and nadir glucose correlated negatively with peak GH levels. WB and FD regimens can induce adult GH and cortisol secretion, but peak responses occur later in the WB regimen. Both regimens are relatively safe, and vomiting was more prevalent in the WB regimen. As age, BMI, and glucose tolerance negatively correlated with peak GH and cortisol levels, the WB regimen may be more effective than the FD regimen in older overweight glucose intolerant patients. C1 [Yuen, Kevin C. J.; Rhoads, Sharon A.; Cook, David M.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. [Biller, Beverly M. K.; Gurel, Michelle H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02459 USA. [Katznelson, Laurence; Chu, Olivia] Stanford Univ, Sch Med, Dept Med, Div Endocrinol, Stanford, CA 94305 USA. [Katznelson, Laurence; Chu, Olivia] Stanford Univ, Sch Med, Dept Neurosurg, Div Endocrinol, Stanford, CA 94305 USA. [Corazzini, Valentina; Salvatori, Roberto] Johns Hopkins Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21287 USA. [Spiller, Kellie; Gordon, Murray B.] Allegheny Gen Hosp, Div Endocrinol, Pittsburgh, PA 15212 USA. RP Yuen, KCJ (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd,Mailcode L607, Portland, OR 97239 USA. EM yuenk@ohsu.edu FU Novo Nordisk FX KCJY, BMKB and MBG have received research grants and consulting honoraria from Novo Nordisk. RS and DMC have received consulting honoraria from Novo Nordisk. This research did not receive any specific grant from any funding agency in the public, commercial or non-profit sector. NR 30 TC 13 Z9 13 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-341X J9 PITUITARY JI Pituitary PD JUN PY 2013 VL 16 IS 2 BP 220 EP 230 DI 10.1007/s11102-012-0407-7 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149CL UT WOS:000319295500013 PM 22806554 ER PT J AU Yu, ZT Liu, B Mukherjee, P Newburg, DS AF Yu, Zhuo-Teng Liu, Bo Mukherjee, Purna Newburg, David S. TI Trametes versicolor Extract Modifies Human Fecal Microbiota Composition In vitro SO PLANT FOODS FOR HUMAN NUTRITION LA English DT Article DE Trametes versicolor; PSP; Fecal microbiota; In vitro fermentation ID BETA-GALACTOSIDASE; FERMENTATION; PROBIOTICS; PREBIOTICS; GROWTH; CANCER; RATS AB Trametes versicolor is a mushroom used as a traditional Chinese medicine (Yun-zhi) for a wide array of seemingly disparate conditions. We hypothesized that many of its multiple purported activities could be mediated through stimulation of beneficial mutualist components of the microbiota. Human fecal microbiota was cultured anaerobically to determine its ability to ferment a common extract of T. versicolor, designated polysaccharide peptide (PSP), and the ability of PSP to alter the composition of the microbial community. The presence of PSP and fructooligosaccharides (FOS, a common prebiotic) in the medium, but not cellulose, significantly increased levels of Bifidobacterium spp. PSP also elevated Lactobacillus spp., while reducing Clostridium spp., Staphylococcus spp. and Enterococcus spp. Levels of Streptococcus spp., Bacteroides spp. and Escherichia did not significantly change. Fermentation of PSP increased the concentration of organic acids (lactate and short-chain fatty acids), decreased the pH, and induced beta-galactosidase and beta-glucosidase activities. The genera of the human microbiota that are promoted by FOS and other prebiotics are also stimulated by the Trametes versicolor extract, PSP. Thus, Trametes versicolor, a common East Asian botanical, contains putative prebiotic agents that alter human gut microbiota and pH. This prebiotic-like activity may help explain some of the plethora of the health benefits attributed to this traditional Chinese medicine. C1 [Yu, Zhuo-Teng; Liu, Bo; Newburg, David S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. RP Newburg, DS (reprint author), Boston Coll, Dept Biol, Program Glycobiol, Higgins Hall,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM david.newburg@bc.edu FU NIH [HD013021, HD059140, AI075563] FX We thank Winsor Health Products, Ltd. for their gift of PSP and partial support, Dr. Gherman Wiederschain for helpful assistance with the manuscript, and the NIH for grants HD013021, HD059140, and AI075563. NR 20 TC 4 Z9 6 U1 2 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0921-9668 J9 PLANT FOOD HUM NUTR JI Plant Food Hum. Nutr. PD JUN PY 2013 VL 68 IS 2 BP 107 EP 112 DI 10.1007/s11130-013-0342-4 PG 6 WC Plant Sciences; Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Plant Sciences; Chemistry; Food Science & Technology; Nutrition & Dietetics GA 149BY UT WOS:000319294200002 PM 23435630 ER EF