FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ahn, AC Gow, BJ Martinsen, OG Zhao, M Grodzinsky, AJ Baikie, ID AF Ahn, Andrew C. Gow, Brian J. Martinsen, Orjan G. Zhao, Min Grodzinsky, Alan J. Baikie, Iain D. TI Applying the Kelvin probe to biological tissues: Theoretical and computational analyses SO PHYSICAL REVIEW E LA English DT Article ID CAPACITANCE; MICROSCOPY; MONOLAYERS; CORROSION; CELLS AB The Kelvin probe measures surface electrical potential without making physical contact with the specimen. It relies on capacitive coupling between an oscillating metal tip that is normal to a specimen's surface. Kelvin probes have been increasingly used to study surface and electrical properties of metals and semiconductors and are capable of detecting material surface potentials with submillivolt resolution at a micrometer spatial scale. Its capability for measuring electrical potential without being confounded by electrode-specimen contact makes extending its use towards biological materials particularly appealing. However, the theoretical basis for applying the Kelvin probe to dielectric or partially conductive materials such as biological tissue has not been evaluated and remains unclear. This study develops the theoretical basis underlying Kelvin probe measurements in five theoretical materials: highly conductive, conductive dielectric with rapid charge relaxation, conductive dielectric with slow charge relaxation, perfect dielectric, and tissue with a bulk serial resistance. These theoretically derived equations are then computationally analyzed using parameters from both theoretical specimens and actual biomaterials-including wet skin, dry skin, cerebrospinal fluid, and tendon. Based on these analyses, a Kelvin probe performs in two distinct ways depending on the charge relaxation rates of the sample: The specimen is treated either as a perfect dielectric or as highly conductive material. Because of their rapid relaxation rate and increased permittivity biomaterials behave similarly to highly conductive materials, such as metal, when evaluated by the Kelvin probe. These results indicate that the Kelvin probe can be readily applied to studying the surface potential of biological tissue. C1 [Ahn, Andrew C.; Gow, Brian J.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Martinsen, Orjan G.] Univ Oslo, Dept Phys, NO-0316 Oslo, Norway. [Martinsen, Orjan G.] Oslo Univ Hosp, Rikshosp, Dept Biomed & Clin Engn, NO-0027 Oslo, Norway. [Zhao, Min] UC Davis Sch Med, Dermatol & Ophthalmol Res Inst Regenerat Cures, Sacramento, CA 95817 USA. [Zhao, Min] Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, Scotland. [Grodzinsky, Alan J.] MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA. [Baikie, Iain D.] KP Technol Ltd, Wick KW1 5LE, Scotland. RP Ahn, AC (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM aahn1@partners.org RI Martinsen, Orjan/M-4459-2014 OI Martinsen, Orjan/0000-0003-1632-4352 FU National Center for Complementary Alternative Medicine (NCCAM) [R21AT005249, P30AT005895] FX This research was supported by Grants No. R21AT005249 and No. P30AT005895 of the National Center for Complementary Alternative Medicine (NCCAM). NR 21 TC 1 Z9 1 U1 1 U2 15 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD JUN 1 PY 2012 VL 85 IS 6 AR 061901 DI 10.1103/PhysRevE.85.061901 PN 1 PG 13 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 951BG UT WOS:000304695000009 PM 23005121 ER PT J AU Myaskovsky, L Doebler, DA Posluszny, DM Dew, MA Unruh, M Crowley-Matoka, M Switzer, GE Dabbs, AD Chang, CCH DiMartini, AF Shapiro, R Tan, HK AF Myaskovsky, Larissa Doebler, Donna Almario Posluszny, Donna M. Dew, Mary Amanda Unruh, Mark Crowley-Matoka, Megan Switzer, Galen E. Dabbs, Annette DeVito Chang, Chung-Chou H. DiMartini, Andrea F. Shapiro, Ron Tan, Henkie TI Rates and correlates of health maintenance behaviors after living kidney donation SO PROGRESS IN TRANSPLANTATION LA English DT Article ID QUALITY-OF-LIFE; TERM-FOLLOW-UP; DONOR NEPHRECTOMY; TRANSPLANTATION; OUTCOMES; CONSEQUENCES; DISEASE; IMPACT AB Context and Objective-Donating a kidney may provide an opportunity for donors to reevaluate their health maintenance behaviors (eg, regular exercise, smoking cessation, medical checkups). Although the effect of donation on donors' health, quality of life, and financial outcomes has received growing attention, no studies have examined whether donation is related to changes in health maintenance behaviors. The study aims were to (I) describe and compare kidney donors' health maintenance behaviors before and after donation, and (2) determine the correlates of health maintenance behaviors after donation. Design, Setting, Participants and Measures-We conducted a telephone-interview study with 85 randomly selected laparoscopic kidney donors in a major US transplant center to assess health behaviors before and after donation, postdonation characteristics (eg, quality of life, postsurgical pain), and demographics. Results-Sample demographics included a median age of 48 years; 55% were female, 82% were white, 71% were married, and 52% were college graduates. Few health behaviors changed significantly from before to after donation. Only the rate of medical checkups increased after donation (P<.001). Logistic regression was used to examine the association of demographics and postdonation characteristics with postdonation health maintenance behaviors, after adjusting for predonation behavior. Older age, higher income, less postsurgical pain, and better physical functioning were associated with more exercise after donation. Longer time since donation was associated with a higher prevalence of obesity. Conclusions-These results may help identify donors who are at greater risk for poor health maintenance behaviors after donation and suggest areas of health behavior that should be the focus of education sessions before donation. (Progress in Transplantation. 2012;22:147-154) (C) 2012 NATCO, The Organization for Transplant Professionals doi: http://dx.doi.org/10.7182/pit2012287 C1 [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Myaskovsky, Larissa; Doebler, Donna Almario; Posluszny, Donna M.; Dew, Mary Amanda; Unruh, Mark; Switzer, Galen E.; Dabbs, Annette DeVito; Chang, Chung-Chou H.; DiMartini, Andrea F.; Shapiro, Ron; Tan, Henkie] Univ Pittsburgh, Pittsburgh, PA USA. [Crowley-Matoka, Megan] Northwestern Univ, Evanston, IL USA. RP Myaskovsky, L (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM larissa.myaskovsky@va.gov FU UPMC Starzl Transplant Institute [XNV 72-069]; VA Health Services Research and Development Division [IIR 06-220] FX Funding for this project was provided by grant XNV 72-069 from the UPMC Starzl Transplant Institute and grant IIR 06-220 from the VA Health Services Research and Development Division. NR 41 TC 4 Z9 4 U1 0 U2 1 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1526-9248 J9 PROG TRANSPLANT JI Prog. Transplant. PD JUN PY 2012 VL 22 IS 2 BP 147 EP 154 DI 10.7182/pit2012287 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 956NA UT WOS:000305095200006 PM 22878071 ER PT J AU Greenfield, BL Venner, KL Kelly, JF Slaymaker, V Bryan, AD AF Greenfield, Brenna L. Venner, Kamilla L. Kelly, John F. Slaymaker, Valerie Bryan, Angela D. TI The Impact of Depression on Abstinence Self-Efficacy and Substance Use Outcomes Among Emerging Adults in Residential Treatment SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE emerging adults; substance use disorder; residential treatment; abstinence self-efficacy; major depressive disorder ID RANDOMIZED CONTROLLED-TRIAL; DRUG-USE CONSEQUENCES; USE DISORDERS; RETEST RELIABILITY; RELAPSE PREVENTION; ALCOHOL-USE; DRINKING; PREDICTORS; PREVALENCE; MECHANISMS AB A large proportion of emerging adults treated for substance use disorder (SUD) present with symptoms of negative affect and major depressive disorder (MDD). However, little is known regarding how these comorbidities influence important mechanisms of treatment response, such as increases in abstinence self-efficacy (ASE). This study tested the degree to which MDD and/or depressive symptoms interacted with during-treatment changes in ASE and examined these variables' relation to outcome at 3 months' posttreatment. Participants (N = 302; 74% male) completed measures at intake, midtreatment, end-of-treatment, and at 3-month follow-up. ASE was measured with the Alcohol and Drug Use Self-Efficacy (ADUSE) scale; depressive symptoms were assessed with the Brief Symptom Inventory 18 (BSI 18) Depression scale; and current MDD diagnoses were deduced from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Random coefficient regression analyses focused on during-treatment changes in ASE, with BSI 18 scores and MDD diagnosis included as moderators. At intake, individuals with MDD or high levels of depressive symptoms had significantly lower ASE, particularly in negative affect situations. No evidence for moderation was found: ASE significantly increased during treatment regardless of MDD status. There was a main effect of BSI 18 Depression scores: those with lower BSI 18 scores had lower ASE scores at each time point. MOD and BSI 18 Depression did not predict 3-month outcome, but similar to previous findings ASE did predict abstinence status at 3 months. Treatment-seeking emerging adults with MDD merit particular clinical attention because of their lower reported self-efficacy throughout treatment. C1 [Greenfield, Brenna L.; Venner, Kamilla L.; Bryan, Angela D.] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87106 USA. [Greenfield, Brenna L.; Venner, Kamilla L.; Bryan, Angela D.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87106 USA. [Kelly, John F.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Slaymaker, Valerie] Hazelden Fdn, Hazelden Grad Sch Addict Studies, Ctr City, MN USA. RP Greenfield, BL (reprint author), Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, 2650 Yale SE,MSC11-6280, Albuquerque, NM 87106 USA. EM brenna@unm.edu FU NIAAA NIH HHS [1R21AA018185-01A, R21 AA018185, R21 AA018185-01A2] NR 52 TC 13 Z9 14 U1 6 U2 15 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2012 VL 26 IS 2 BP 246 EP 254 DI 10.1037/a0026917 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 956NX UT WOS:000305097500008 PM 22288980 ER PT J AU Mattson, RE O'Farrell, TJ Lofgreen, AM Cunningham, K Murphy, CM AF Mattson, Richard E. O'Farrell, Timothy J. Lofgreen, Ashton M. Cunningham, Karlene Murphy, Christopher M. TI The Role of Illicit Substance Use in a Conceptual Model of Intimate Partner Violence in Men Undergoing Treatment for Alcoholism SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE violence; intimate partners; substance use; substance abuse; drugs ID DRUG-USE; PHYSICAL AGGRESSION; DYADIC ADJUSTMENT; STRUCTURAL MODELS; EARLY MARRIAGE; ABUSE; MEDIATION; COEFFICIENT; STATISTICS; VALIDATION AB Illicit substance use (ISU) predicts intimate partner violence (IPV) above and beyond alcohol use and other known IPV correlates. Stuart and colleagues (2008) provided evidence for a theoretical framework by which ISU contributes both directly and indirectly to IPV. We sought to replicate and extend their findings using data from 181 married or cohabiting heterosexual couples in which the male had recently begun a substance abuse treatment program and met criteria for alcohol dependence (97%) or abuse (3%). Using SEM, we found that (a) Stuart et al.'s model provided a good fit to the data; (b) men's cocaine use and women's sedative use emerged as particularly relevant to their respective perpetration of IPV; (c) a positive association between men's antisociality and physical aggression was mediated by increased stimulant use; and (d) the specific pattern of IPV predicted by women's sedative use differed across levels of aggression severity. These findings not only highlight the direct role of ISU in relationship aggression, but also support a larger theory-driven model comprising various proximal and distal precursors of IPV. C1 [Mattson, Richard E.; Lofgreen, Ashton M.; Cunningham, Karlene] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [O'Farrell, Timothy J.] VA Boston Hlth Care Syst, Dept Psychiat, Families & Addict Program, Boston, MA USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Murphy, Christopher M.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. RP O'Farrell, TJ (reprint author), VA Boston, VAMC 116B1,940 Belmont St, Brockton, MA 02301 USA. EM timothy_ofarrell@hms.harvard.edu FU NIAAA NIH HHS [R01 AA010796, R01 AA010796-04] NR 67 TC 17 Z9 17 U1 1 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2012 VL 26 IS 2 BP 255 EP 264 DI 10.1037/a0025030 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 956NX UT WOS:000305097500009 PM 21875168 ER PT J AU Green, KE Feinstein, BA AF Green, Kelly E. Feinstein, Brian A. TI Substance Use in Lesbian, Gay, and Bisexual Populations: An Update on Empirical Research and Implications for Treatment SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE substance use; lesbian; gay; bisexual; review; treatment ID CLUB DRUG-USE; ALCOHOL-RELATED PROBLEMS; HOMOSEXUALLY ACTIVE MEN; NEW-YORK-CITY; SEXUAL ORIENTATION; ABUSE TREATMENT; RISK BEHAVIORS; USE DISORDERS; COLLEGE-STUDENTS; RANDOMIZED-TRIAL AB Historically, substance use problems were thought to be more prevalent in lesbian, gay, and bisexual (LGB) populations, and correcting skewed perceptions about substance abuse among LGB individuals is critically important. This review provides an update on empirical evidence on LGB substance use patterns and treatment outcome, with specific focus on clinical implications of findings. Compared to earlier studies, the recent research included in this review has used more sophisticated methodologies and more representative samples, and also has investigated multiple dimensions of sexual orientation in relation to substance use patterns. Findings from recent research suggest that lesbians and bisexual women are at greater risk for alcohol and drug use disorders and related problems, and that gay and bisexual men are at greater risk for illicit drug use and related problems. Several sociocultural factors have emerged as correlates of substance use patterns in LGB populations (e.g., affiliation with gay culture, HIV status), and several demographic characteristics (e.g., female, older age) do not appear to be as robust of protective factors against substance abuse for LGB individuals compared to heterosexual populations. Bisexual identity and/or behavior in particular seem to be related to increased risk for substance abuse. In terms of treatment outcome, limitations of extant research prevent conclusions about the relative impact of LGB-specific interventions, and further research that includes women and uses more equivalent comparison interventions is needed. Clinical implications of research findings are discussed for case identification, selection of treatment goals (e.g., moderation vs. abstinence), targets for intervention, and specific treatment modalities. C1 [Green, Kelly E.] VA Boston Healthcare Syst, Psychol Serv, Brockton, MA 02310 USA. [Green, Kelly E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Feinstein, Brian A.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA. RP Green, KE (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 940 Belmont St, Brockton, MA 02310 USA. EM Kelly.Green3@va.gov FU NIAAA NIH HHS [T32 AA007569, T32 AA007569-05, T32 AA07569] NR 68 TC 49 Z9 49 U1 5 U2 21 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 2012 VL 26 IS 2 BP 265 EP 278 DI 10.1037/a0025424 PG 14 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 956NX UT WOS:000305097500010 PM 22061339 ER PT J AU Carmody, TP Delucchi, K Simon, JA Duncan, CL Solkowitz, SN Huggins, J Lee, SK Hall, SM AF Carmody, Timothy P. Delucchi, Kevin Simon, Joel A. Duncan, Carol L. Solkowitz, Sharon N. Huggins, Joy Lee, Sharon K. Hall, Sharon M. TI Expectancies Regarding the Interaction Between Smoking and Substance Use in Alcohol-Dependent Smokers in Early Recovery SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE smoking cessation; tobacco use; nicotine dependence; alcohol dependence; expectancies ID ADDICTION SEVERITY INDEX; FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE DEPENDENCE; ABUSE TREATMENT; CESSATION INTERVENTIONS; ABSTINENCE; DISORDERS; TOBACCO; METAANALYSIS; INDIVIDUALS AB The purpose of this study was to investigate expectancies regarding the interaction between cigarette smoking and use of alcohol among alcohol-dependent smokers in early recovery, using the Nicotine and Other Substances Interaction Expectancies Questionnaire (NOSIE). Participants were 162 veterans, 97% male, with a mean age of 50 years, enrolled in a clinical trial aimed at determining the efficacy of an intensive smoking cessation intervention versus usual care. At baseline, participants were assessed on measures of smoking behavior, abstinence thoughts about alcohol and tobacco use, symptoms of depression, and smoking-substance use interaction expectancies. In addition, biologically verified abstinence from tobacco and alcohol was assessed at 26 weeks. Participants reported that they expected smoking to have less of an impact on substance use than substance use has on smoking (p < .001). Severity of depressive symptoms was significantly associated with the expectancy that smoking provides a way of coping with the urge to use other substances (p < .01). The expectation that smoking increases substance urges/use was predictive of prospectively measured and biologically verified abstinence from smoking at 26 weeks (p < .03). The results add to our knowledge of smoking-substance use interaction expectancies among alcohol-dependent smokers in early recovery and will inform the development of more effective counseling interventions for concurrent alcohol and tobacco use disorders. C1 [Carmody, Timothy P.; Simon, Joel A.; Duncan, Carol L.; Solkowitz, Sharon N.; Huggins, Joy; Lee, Sharon K.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Delucchi, Kevin; Hall, Sharon M.] Univ Calif San Francisco, Treatment Res Ctr, Dept Psychiat, San Francisco, CA 94143 USA. RP Carmody, TP (reprint author), Vet Affairs Med Ctr, Mental Hlth Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.carmody@va.gov FU NIDA NIH HHS [P50 DA09253, P50 DA009253-09, P50 DA009253] NR 36 TC 8 Z9 8 U1 1 U2 4 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 2012 VL 26 IS 2 BP 358 EP 363 DI 10.1037/a0024424 PG 6 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 956NX UT WOS:000305097500021 PM 21707127 ER PT J AU Hess, DR AF Hess, Dean R. TI The Growing Role of Noninvasive Ventilation in Patients Requiring Prolonged Mechanical Ventilation SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 49th Respiratory Care Journal Conference on Chronically Critically Ill Patient CY SEP 09-10, 2011 CL St Petersburg, FL SP Amer Resp Care Fdn DE amyotrophic lateral sclerosis; bi-level pressure ventilation; chronic obstructive pulmonary disease; cystic fibrosis; Duchenne muscular dystrophy; noninvasive ventilation; obesity hypoventilation syndrome; restrictive thoracic disorder ID POSITIVE-PRESSURE VENTILATION; OBESITY-HYPOVENTILATION SYNDROME; OBSTRUCTIVE PULMONARY-DISEASE; DUCHENNE MUSCULAR-DYSTROPHY; CHRONIC RESPIRATORY-FAILURE; STABLE HYPERCAPNIC COPD; RANDOMIZED CROSSOVER TRIAL; PROPORTIONAL ASSIST VENTILATION; AMYOTROPHIC-LATERAL-SCLEROSIS; NOCTURNAL NASAL VENTILATION AB For many patients with chronic respiratory failure requiring ventilator support, noninvasive ventilation (NIV) is preferable to invasive support by tracheostomy. Currently available evidence does not support the use of nocturnal NIV in unselected patients with stable COPD. Several European studies have reported benefit for high intensity NIV, in which setting of inspiratory pressure and respiratory rate are selected to achieve normocapnia. There have also been studies reporting benefit for the use of NIV as an adjunct to exercise training. NIV may be useful as an adjunct to airway clearance techniques in patients with cystic fibrosis. Accumulating evidence supports the use of NIV in patients with obesity hypoventilation syndrome. There is considerable observational evidence supporting the use of NIV in patients with chronic respiratory failure related to neuromuscular disease, and one randomized controlled trial reported that the use of NIV was life-prolonging in patients with amyotrophic lateral sclerosis. A variety of interfaces can be used to provide NIV in patients with stable chronic respiratory failure. The mouthpiece is an interface that is unique in this patient population, and has been used with success in patients with neuromuscular disease. Bi-level pressure ventilators are commonly used for NIV, although there are now a new generation of intermediate ventilators that are portable, have a long battery life, and can be used for NIV and invasive applications. Pressure support ventilation, pressure controlled ventilation, and volume controlled ventilation have been used successfully for chronic applications of NIV. New modes have recently become available, but their benefits await evidence to support their widespread use. The success of NIV in a given patient population depends on selection of an appropriate patient, selection of an appropriate interface, selection of an appropriate ventilator and ventilator settings, the skills of the clinician, the motivation of the patient, and the support of the family. 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, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 192 TC 16 Z9 17 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 2012 VL 57 IS 6 BP 900 EP 920 DI 10.4187/respcare.01692 PG 21 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 955UY UT WOS:000305047600006 PM 22663966 ER PT J AU Atwood, CW AF Atwood, Charles W., Jr. TI "The Times They Are A Changin:" Home Diagnosis of Sleep Apnea Has Arrived Commentary on Rosen et al. A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: The HomePAP Study. SLEEP 2012;35:757-767 SO SLEEP LA English DT Editorial Material ID OUTCOMES C1 [Atwood, Charles W., Jr.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Med Ctr, UPMC Sleep Med Ctr, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Pulm Sect, Pittsburgh, PA USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Sleep Disorders Program, Pittsburgh, PA USA. RP Atwood, CW (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Med Ctr, UPMC Sleep Med Ctr, 3459 5th Ave,NW628 MUH, Pittsburgh, PA 15213 USA. EM atwoodcw@upmc.edu NR 8 TC 2 Z9 2 U1 0 U2 0 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 2012 VL 35 IS 6 BP 735 EP 736 DI 10.5665/sleep.1848 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 952CM UT WOS:000304767300003 PM 22654184 ER PT J AU Kim, Y Bolortuya, Y Chen, LC Basheer, R McCarley, RW Strecker, RE AF Kim, Youngsoo Bolortuya, Yunren Chen, Lichao Basheer, Radhika McCarley, Robert W. Strecker, Robert E. TI Decoupling of Sleepiness from Sleep Time and Intensity during Chronic Sleep Restriction: Evidence for a Role of the Adenosine System SO SLEEP LA English DT Article DE Chronic sleep restriction; rat; allostasis; sleep latency; adenosine; receptor ID HOMEOSTATIC REGULATION; DOSE-RESPONSE; A(1) RECEPTOR; RISK-FACTOR; DEPRIVATION; RATS; BRAIN; RECOVERY; DURATION; MICE AB Study Objective: Sleep responses to chronic sleep restriction (CSR) might be very different from those observed after short-term total sleep deprivation. For example, after sleep restriction continues for several consecutive days, animals no longer express compensatory increases in daily sleep time and sleep intensity. However, it is unknown if these allostatic, or adaptive, sleep responses to CSR are paralleled by behavioral and neurochemical measures of sleepiness. Design: This study was designed to investigate CSR-induced changes in (1) sleep time and intensity as a measure of electrophysiological sleepiness, (2) sleep latency as a measure of behavioral sleepiness, and (3) brain adenosine A1 (A1R) and A2a receptor (A2aR) mRNA levels as a putative neurochemical correlate of sleepiness. Subjects: Male Sprague-Dawley rats Interventions: A 5-day sleep restriction (SR) protocol consisting of 18-h sleep deprivation and 6-h sleep opportunity each day. Measurement and Results: Unlike the first SR day, rats did not sleep longer or deeper on days 2 through 5, even though they exhibited significant elevations of behavioral sleepiness throughout all 5 SR days. For all SR days and recovery day 1, A1R mRNA in the basal forebrain was maintained at elevated levels, whereas A2aR mRNA in the frontal cortex was maintained at reduced levels. Conclusion: CSR leads to a decoupling of sleepiness from sleep time and sleep intensity, suggesting that there are at least two different sleep regulatory systems: one mediating sleepiness (homeostatic) and the other mediating sleep time/intensity (allostatic). The time course of changes observed in adenosine receptor mRNA levels suggests that the basal forebrain and cortical adenosine system might mediate sleepiness rather than sleep time or intensity. C1 [Kim, Youngsoo] VA Boston Healthcare Syst, Res Serv, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Res Serv, Brockton, MA 02301 USA. RP Kim, Y (reprint author), VA Boston Healthcare Syst, Res Serv, 151-C,940 Belmont St, Brockton, MA 02301 USA. EM youngsoo_kim@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veterans Affairs Medical Research Service [T32 HL07901, R37 MH039683, P50 HL060292, HL095491] FX We thank Ritchie E. Brown and Michael A. Christie for helpful discussions. This research was supported by: Department of Veterans Affairs Medical Research Service Award (RES), T32 HL07901 (YK), R37 MH039683 (RWM & RES), P50 HL060292 (RES & RWM), HL095491 (RWM & RES). NR 36 TC 21 Z9 21 U1 2 U2 7 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 2012 VL 35 IS 6 BP 861 EP 869 DI 10.5665/sleep.1890 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 952CM UT WOS:000304767300024 PM 22654205 ER PT J AU Biering-Sorensen, F Krassioukov, A Alexander, MS Donovan, W Karlsson, AK Mueller, G Perkash, I Sheel, AW Wecht, J Schilero, GJ AF Biering-Sorensen, F. Krassioukov, A. Alexander, M. S. Donovan, W. Karlsson, A-K Mueller, G. Perkash, I. Sheel, A. William Wecht, J. Schilero, G. J. TI International Spinal Cord Injury Pulmonary Function Basic Data Set SO SPINAL CORD LA English DT Article DE spinal cord injury; international data set; pulmonary function; pneumonia; sleep apnea; ventilator ID FORCED VITAL CAPACITY; MORTALITY; SLEEP; DEATH; FEV1; FVC AB Objectives: To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. Setting: International. Methods: The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. Results: The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion, if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk). Spinal Cord (2012) 50, 418-421; doi:10.1038/sc.2011.183; published online 24 January 2012 C1 [Biering-Sorensen, F.] Rigshosp, Clin Spinal Cord Injuries, Ctr Neurosci, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, DK-2100 Copenhagen O, Denmark. [Krassioukov, A.; Sheel, A. William] Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada. [Krassioukov, A.; Sheel, A. William] Vancouver Coastal Hlth, Vancouver, BC, Canada. [Alexander, M. S.] Renown Rehabil Hosp, Reno, NV USA. [Donovan, W.] Univ Texas Hlth Sci Ctr, Baylor Coll Med, Houston, TX USA. [Karlsson, A-K] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Mueller, G.] Swiss Parapleg Ctr, Clin Trial Unit, Nottwil, Switzerland. [Perkash, I.] Stanford Univ, Palo Alto, CA 94304 USA. [Perkash, I.] Vet Adm Palo Alto, Palo Alto, CA USA. [Wecht, J.; Schilero, G. J.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Wecht, J.; Schilero, G. J.] Mt Sinai Sch Med, New York, NY USA. RP Biering-Sorensen, F (reprint author), RIGSHOSP TH2091, Clin Spinal Cord Injuries, Ctr Neurosci, 9 Blegdamsvej, DK-2100 Copenhagen O, Denmark. EM finbs@rh.dk FU Coloplast A/S, Denmark FX Coloplast A/S, Denmark has supported the work with this Data Set with an unconditional grant. We are thankful for comments and suggestions received from Lawrence Vogel, Susan Charlifue, Gordana Savic and Michael DeVivo. NR 15 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUN PY 2012 VL 50 IS 6 BP 418 EP 421 DI 10.1038/sc.2011.183 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 951LC UT WOS:000304721100005 PM 22270192 ER PT J AU Lubitz, CC Nagarkatti, SS Faquin, WC Samir, AE Hassan, MC Barbesino, G Ross, DS Randolph, GW Gaz, RD Stephen, AE Hodin, RA Daniels, GH Parangi, S AF Lubitz, Carrie C. Nagarkatti, Sushruta S. Faquin, William C. Samir, Anthony E. Hassan, Maria C. Barbesino, Giuseppe Ross, Douglas S. Randolph, Gregory W. Gaz, Randall D. Stephen, Antonia E. Hodin, Richard A. Daniels, Gilbert H. Parangi, Sareh TI Diagnostic Yield of Nondiagnostic Thyroid Nodules Is Not Altered by Timing of Repeat Biopsy SO THYROID LA English DT Article ID FINE-NEEDLE-ASPIRATION; MANAGEMENT AB Background: Guidelines from the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference recommend a repeat fine-needle aspiration biopsy (FNAB) after 3 months for thyroid nodules with a nondiagnostic (ND) result. Our aims were to assess which factors influenced their clinical management and to determine if the timing of the repeat FNAB affects the diagnostic yield. Methods: A retrospective institutional review of 298 patients from 1/2006 to 12/2007 with an ND FNAB was performed. The factors influencing the next step in management, including age, gender, history of radiation, presence of Hashimoto's thyroiditis, thyroid-stimulating hormone levels, and ultrasound characteristics, were evaluated. The effect of the time of the repeat FNABs on their diagnostic yield was assessed. Results: Of the 298 patients in our cohort, 9% were referred directly for surgery, 76% had a repeat FNAB, and 15% were observed. Tumor size was the only independent variable correlated with treatment strategy after a ND FNAB. There was not a significant difference in diagnostic yields between repeat FNABs performed earlier than 3 months compared to those preformed later (p=0.58). Conclusion: The timing of repeat FNAB for an initial ND FNAB does not affect diagnostic yield of the repeat FNAB. C1 [Lubitz, Carrie C.; Nagarkatti, Sushruta S.; Hassan, Maria C.; Randolph, Gregory W.; Gaz, Randall D.; Stephen, Antonia E.; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Endocrine Surg Unit, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Barbesino, Giuseppe; Ross, Douglas S.; Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Thyroid Unit, Boston, MA 02114 USA. RP Lubitz, CC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Endocrine Surg Unit, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM clubitz@partners.org OI Samir, Anthony/0000-0002-7801-8724 FU NCI NIH HHS [R01 CA149738] NR 11 TC 19 Z9 19 U1 0 U2 1 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 2012 VL 22 IS 6 BP 590 EP 594 DI 10.1089/thy.2011.0442 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 955EZ UT WOS:000305001200006 PM 22667452 ER PT J AU Kim, SB Williams, SB Cheng, SC Sanda, MG Wagner, AA AF Kim, Sarah B. Williams, Stephen B. Cheng, Su-Chun Sanda, Martin G. Wagner, Andrew A. TI Evaluation of Patient-reported Quality-of-life Outcomes After Renal Surgery SO UROLOGY LA English DT Article ID RECOVERY EVALUATION CARE; CELL CARCINOMA; PROSTATE-CANCER; HEALTH SURVEY; VALIDATION; CONVALESCENCE; NEPHRECTOMY; IMPACT; MEN AB OBJECTIVE To assess the feasibility of 2 patient-reported health-related quality of life (HRQOL) instruments, Convalescence and Recovery Evaluation (CARE), and SF-12, as tools for evaluating HRQOL outcome consequences after renal surgery, and to determine which domains of these HRQOL instruments are most sensitive to HRQOL outcome effects of renal surgery. METHODS Patients completed CARE and SF-12 preoperatively (baseline) and at 2, 4, 12, and 24 weeks after surgery. Clinical data, patient response rate, HRQOL changes over time, and likelihood of patient return to baseline HRQOL were evaluated. RESULTS Seventy-one patients were enrolled. Sixty patients completed the baseline and at least 1 follow-up set of questionnaires. The CARE pain, gastrointestinal (GI), and activity domain scores and the SF-12 physical composite score (PCS) were sensitive to changes in HRQOL (all P<.05), whereas other domain subscores of these instruments did not change from presurgical baseline to postsurgical follow-up. Postsurgical HRQOL effects detected by the CARE pain, GI, and activity domains, and SF-12 PCS were most evident at 2 weeks (all P<.001). The CARE composite score demonstrated that 74% and 50% of patients returned to within 90% of baseline 4 weeks after radical and partial nephrectomy, respectively. CONCLUSION Evaluation of patient-reported HRQOL outcomes after renal surgery is feasible; our findings suggest that the activity, pain, and GI domains of CARE and PCS subscores of the SF-12 are sensitive measures of HRQOL outcome consequences of renal surgery and represent appropriate measures of either care quality or comparative effectiveness analyses of robotic, laparoscopic, and open renal surgery. UROLOGY 79: 1268-1273, 2012. (c) 2012 Elsevier Inc. C1 [Wagner, Andrew A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Wagner, Andrew A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Urol, Boston, MA 02215 USA. St Joseph Hosp, Ctr Canc Prevent & Treatment, Div Urol Oncol, Orange, CA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Wagner, AA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, 330 Brookline Ave,Rabb 440, Boston, MA 02215 USA. EM awagner@bidmc.harvard.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 FU Dana Farber/Harvard Cancer Center: Kidney Cancer SPORE; Kidney Cancer Association FX This project was supported by a joint Developmental Award from the Dana Farber/Harvard Cancer Center: Kidney Cancer SPORE and the Kidney Cancer Association. NR 16 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2012 VL 79 IS 6 BP 1268 EP 1273 DI 10.1016/j.urology.2012.02.047 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 951KX UT WOS:000304720600023 PM 22542421 ER PT J AU Saboo, SS Krajewski, KM Jagannathan, JP Ramaiya, N AF Saboo, Sachin S. Krajewski, Katherine M. Jagannathan, Jyothi P. Ramaiya, Nikhil TI IVC Tumor Thrombus: An Advanced Case of Rare Extraosseous Ewing Sarcoma of the Adrenal Gland SO UROLOGY LA English DT Editorial Material AB Extraosseous Ewing sarcoma (ES) of the adrenal gland is a rare, aggressive tumor of young adults, with <10 cases reported. We present the radiological findings of an unusual case of adrenal and renal vein tumor thrombosis extending into the inferior vena cava, secondary to ES of the adrenal gland in a 26-year-old female. UROLOGY 79: e77-e78, 2012. (c) 2012 Elsevier Inc. C1 [Saboo, Sachin S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. [Saboo, Sachin S.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Saboo, SS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM ssaboo@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2012 VL 79 IS 6 BP E77 EP E78 DI 10.1016/j.urology.2012.03.008 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 951KX UT WOS:000304720600001 PM 22656426 ER PT J AU Todoran, TM Connors, G Engelson, BA Sobieszczyk, PS Eisenhauer, AC Kinlay, S AF Todoran, Thomas M. Connors, Gerard Engelson, Brian A. Sobieszczyk, Piotr S. Eisenhauer, Andrew C. Kinlay, Scott TI Femoral artery percutaneous revascularization for patients with critical limb ischemia: Outcomes compared to patients with claudication over 2.5 years SO VASCULAR MEDICINE LA English DT Article DE amputation; angioplasty; atherosclerosis; claudication (see intermittent claudication); femoral artery; ischemia; leg; longitudinal studies; outcome assessment (health care); peripheral arterial disease ID INFRAINGUINAL BYPASS; LOWER-EXTREMITY; INTERVENTIONS; ANGIOPLASTY; SALVAGE; DISEASE; SURGERY; EVENTS; TRIAL; MULTICENTER AB Patients with critical limb ischemia have higher rates of death and amputation after revascularization compared to patients with intermittent claudication. However, the differences in patency after percutaneous revascularization of the superficial femoral artery are uncertain and impact the long-term risk of amputation and function in critical limb ischemia. We identified 171 limbs from 136 consecutive patients who had angioplasty and/or stenting for superficial femoral artery stenoses or occlusions from July 2003 through June 2007. Patients were followed for primary and secondary patency, death and amputation up to 2.5 years, and 111 claudicants were retrospectively compared to the 25 patients with critical limb ischemia. Successful percutaneous revascularization occurred in 128 of 142 limbs (90%) with claudication versus 25 of 29 limbs (86%) with critical limb ischemia (p = 0.51). Overall secondary patency at 2.5 years was 91% for claudication and 88% for critical limb ischemia. In Cox proportional hazards models, percutaneous revascularization for critical limb ischemia had similar long-term primary patency (adjusted hazard ratio = 1.1, 95% CI = 0.4, 2.6; p = 0.89) and secondary patency (adjusted hazard ratio = 1.1, 95% CI = 0.2, 6.0; p = 0.95) to revascularization for claudication. Patients with critical limb ischemia had higher mortality and death rates compared to claudicants, with prior statin use associated with less death (p = 0.034) and amputation (p = 0.010), and prior clopidogrel use associated with less amputation (p = 0.034). In conclusion, percutaneous superficial femoral artery revascularization is associated with similar long-term durability in both groups. Intensive treatment of atherosclerosis risk factors and surveillance for restenosis likely contribute to improving the long-term outcomes of both manifestations of peripheral artery disease. C1 [Kinlay, Scott] VA Boston Healthcare Syst, Intervent Cardiol & Vasc Med, Div Cardiovasc, Boston, MA USA. [Todoran, Thomas M.] Med Univ S Carolina, Div Cardiovasc, Charleston, SC 29425 USA. [Connors, Gerard] Princess Alexandra Hosp, Div Cardiovasc, Brisbane, Qld 4102, Australia. [Connors, Gerard] Greenslopes Hosp, Brisbane, Qld, Australia. [Connors, Gerard] Univ Queensland, Brisbane, Qld, Australia. [Engelson, Brian A.; Sobieszczyk, Piotr S.; Eisenhauer, Andrew C.; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc, Intervent & Vasc Med Sect, Boston, MA 02115 USA. [Engelson, Brian A.; Sobieszczyk, Piotr S.; Eisenhauer, Andrew C.; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Intervent Cardiol & Vasc Med, Div Cardiovasc, W Roxbury, MA 02132 USA. EM Scott.kinlay@va.gov NR 23 TC 4 Z9 4 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 2012 VL 17 IS 3 BP 138 EP 144 DI 10.1177/1358863X12440141 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 951KR UT WOS:000304719900002 PM 22496125 ER PT J AU Weinberg, I Giri, J Calfon, MA Hawkins, BM Weinberg, MD Schainfeld, RM Jaff, MR AF Weinberg, Ido Giri, Jay Calfon, Marcella A. Hawkins, Beau M. Weinberg, Mitchell D. Schainfeld, Robert M. Jaff, Michael R. TI Anatomic correlates of supranormal ankle brachial indices (ABI) SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Weinberg, Ido; Giri, Jay; Calfon, Marcella A.; Hawkins, Beau M.; Weinberg, Mitchell D.; Schainfeld, Robert M.; Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 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 2012 VL 17 IS 3 MA 10 BP 200 EP 201 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 951KR UT WOS:000304719900019 ER PT J AU Baron, JM Johnson, SM Ledford-Kraemer, MR Hayward, CP Meijer, P Van Cott, EM AF Baron, Jason M. Johnson, Stephen M. Ledford-Kraemer, Marlies R. Hayward, Catherine P. Meijer, Piet Van Cott, Elizabeth M. TI Protein C Assay Performance An Analysis of North American Specialized Coagulation Laboratory Association Proficiency Testing Results SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Protein C; Quality assurance; Hypercoagulability AB To determine the performance and frequency of protein C reagents currently used by clinical laboratories, we analyzed North American Specialized Coagulation Laboratory Association (NASCOLA) protein C proficiency testing data from 6 surveys conducted in 2009 and 2010 (2009-1 to 2009-3 and 2010-1 to 2010-3). Interlaboratory coefficients of variation (CV) for commonly used reagents on a survey with normal protein C ranged from 8% to 12% for antigenic assays, from 4% to 7% for chromogenic activity assays, and from 7% to 22% for clot-based activity assays. CVs for commonly used reagents on specimens with abnormal protein C ranged from 15% to 24% for antigenic, 4% to 11% for chromogenic, and 10% to 17% for clot-based assays (averaged across 3 surveys). Some reagents were used by relatively few laboratories and therefore additional study may be needed for those reagents. For all commonly used reagents, biases were usually small and often not statistically significant. All assessed reagents were clinically accurate, and were considered acceptable options for a specialized coagulation laboratory. C1 [Baron, Jason M.; Van Cott, Elizabeth M.] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Johnson, Stephen M.] Tufts Med Ctr, Dept Pathol, Boston, MA USA. [Ledford-Kraemer, Marlies R.] CLOT ED, Islamorada, FL USA. [Hayward, Catherine P.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Hayward, Catherine P.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. RP Van Cott, EM (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, GRJ 235,55 Fruit St, Boston, MA 02114 USA. OI Hayward, Catherine/0000-0002-2843-0817 NR 8 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2012 VL 137 IS 6 BP 909 EP 915 DI 10.1309/AJCP8MWU4QSTCLPU PG 7 WC Pathology SC Pathology GA 949KS UT WOS:000304575700008 PM 22586050 ER PT J AU Sheehy, E O'Connor, KJ Luskin, RS Howard, RJ Cornell, D Finn, J Mone, T Selck, FW Delmonico, FL AF Sheehy, E. O'Connor, K. J. Luskin, R. S. Howard, R. J. Cornell, D. Finn, J. Mone, T. Selck, F. W. Delmonico, F. L. TI Investigating Geographic Variation in Mortality in the Context of Organ Donation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Donation rate; donation service area; organ allocation; organ donation ID UNITED-STATES; PROCUREMENT; TRANSPLANTATION; PERFORMANCE; DONORS; TRENDS AB Organ procurement organizations (OPOs) report a nearly fourfold difference in donor availability as measured by eligible deaths per million population (PMP) based on hospital referrals. We analyzed whether mortality data help explain geographic variation in organ supply as measured by the number of eligible deaths for organ donation. Using the 2007 National Center for Health Statistics mortality data, we analyzed deaths occurring in acute care hospitals, aged = 70 years from cerebrovascular accidents and trauma. These deaths were mapped at the county level and compared to eligible deaths reported by OPOs. In 2007, there were 2 428 343 deaths reported in the United States with 42 339 in-hospital deaths = 70 years from cerebrovascular accidents (CVA) or trauma that were correlated with eligible deaths PMP (r2= 0.79.) Analysis revealed a broad range in the death rate across OPOs: trauma deaths: 44118 PMP; deaths from CVA: 34118 PMP; and combined CVA and trauma: 91229 PMP. Mortality data demonstrate that deaths by neurologic criteria of people who are likely to be suitable deceased donors are not evenly distributed across the nation. These deaths are correlated with eligible deaths for organ donation. Regional availability of organs is affected by deaths which should be accounted for in the organ allocation system. C1 [Sheehy, E.; Luskin, R. S.] New England Organ Bank Inc, Waltham, MA USA. [O'Connor, K. J.] LifeCtr NW, Bellevue, WA USA. [Howard, R. J.; Cornell, D.] LifeQuest Organ Recovery Serv, Gainesville, FL USA. [Finn, J.] Midwest Transplant Network, Westwood, KS USA. [Mone, T.] OneLegacy, Los Angeles, CA USA. [Selck, F. W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Delmonico, F. L.] New England Organ Bank Inc, Boston, MA USA. [Delmonico, F. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sheehy, E (reprint author), New England Organ Bank Inc, Waltham, MA USA. EM ellenhsheehy@gmail.com NR 20 TC 14 Z9 14 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2012 VL 12 IS 6 BP 1598 EP 1602 DI 10.1111/j.1600-6143.2011.03981.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 948SM UT WOS:000304522900031 PM 22443186 ER PT J AU Sheehan, WJ Hoffman, EB Fu, CX Baxi, SN Bailey, A King, EM Chapman, MD Lane, JP Gaffin, JM Permaul, P Gold, DR Phipatanakul, W AF Sheehan, William J. Hoffman, Elaine B. Fu, Chunxia Baxi, Sachin N. Bailey, Ann King, Eva-Maria Chapman, Martin D. Lane, Jeffrey P. Gaffin, Jonathan M. Permaul, Perdita Gold, Diane R. Phipatanakul, Wanda TI Endotoxin exposure in inner-city schools and homes of children with asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID DAY-CARE-CENTERS; HOUSE-DUST ENDOTOXIN; ENVIRONMENTAL INTERVENTION; AGE-CHILDREN; CHILDHOOD; ALLERGEN; WHEEZE; DETERMINANTS; COCKROACH; SYMPTOMS AB Background: Endotoxins are stimulators of the immune system and, despite their potential to protect against allergy, have been associated with early wheezing and asthma morbidity. Objective: To compare inner-city school endotoxin exposure with home endotoxin exposure in children with asthma. Methods: Students with asthma were recruited from 12 urban elementary schools. Settled and airborne dust samples, linked to enrolled students, were collected from school classrooms, gymnasiums, and cafeterias twice during the academic year. For comparison, settled dust was collected once from the bedrooms of students with asthma. Results: Two hundred twenty-nine school settled dust samples and 118 bedroom settled dust samples were collected and analyzed for endotoxin. The median endotoxin concentration for school samples was 13.4 EU/mg (range, 0.7-360.7 EU/mg) and for home samples was 7.0 EU/mg (range = LLOD-843.0 EU/mg). The median concentration within each individual school varied from 6.6 EU/mg to 24.0 EU/mg. One hundred four students with asthma had matched classroom and bedroom endotoxin exposure measurements performed in the same season and demonstrated significantly higher concentrations of endotoxin in the students' classrooms (mean log value, 1.13 vs 0.99, P = .04). The median of the classrooms was 12.5 EU/mg compared with their bedrooms, with a median of 7.0 EU/mg. Within the school environment, no significant difference was seen between the fall and spring samples (mean log value 1.14 vs 1.09; P = .35). Conclusion: Inner-city children with asthma were exposed to higher concentrations of endotoxin in their classrooms as compared with their bedrooms. Further studies are needed to evaluate school endotoxin exposure as a factor in asthma morbidity. (C) 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Sheehan, William J.; Baxi, Sachin N.; Phipatanakul, Wanda] Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02115 USA. [Sheehan, William J.; Baxi, Sachin N.; Gaffin, Jonathan M.; Permaul, Perdita; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Hoffman, Elaine B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fu, Chunxia; Bailey, Ann; Gold, Diane R.; Phipatanakul, Wanda] Brigham & Womens Hosp, Channing Lab, Div Resp Epidemiol, Boston, MA 02115 USA. [King, Eva-Maria; Chapman, Martin D.] Indoor Biotechnol Inc, Charlottesville, VA USA. [Gaffin, Jonathan M.] Childrens Hosp, Dept Pediat, Div Pulmonol, Boston, MA 02115 USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy & Immunol, Boston, MA 02114 USA. RP Phipatanakul, W (reprint author), Childrens Hosp, Dept Pediat, Div Allergy & Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU Foundation of ACAAI; NIH [R01 AI 073964, R01 AI 073964-02S1]; Harvard Catalyst Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; [T32-AI-007512] FX Foundation of ACAAI, Young Faculty Support Award (Dr. Phipatanakul) NIH Grants: R01 AI 073964 and R01 AI 073964-02S1. Dr. Sheehan received partial support from T32-AI-007512. This work was conducted with support from Harvard Catalyst Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. NR 31 TC 23 Z9 23 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUN PY 2012 VL 108 IS 6 BP 418 EP 422 DI 10.1016/j.anai.2012.04.003 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 948SC UT WOS:000304521900008 PM 22626594 ER PT J AU Kradin, RL Sheldon, TA Nielsen, P Selig, M Hunt, J AF Kradin, Richard L. Sheldon, Thomas A. Nielsen, Petur Selig, Martin Hunt, Jennifer TI Malacoplakia of the tongue complicating the site of irradiation for squamous cell carcinoma with review of the literature SO ANNALS OF DIAGNOSTIC PATHOLOGY LA English DT Review DE Malacoplakia; Gram-negative bacilli; Tongue; Infection; Macrophage ID MALAKOPLAKIA; PATHOGENESIS AB Malacoplakia is a benign and uncommon inflammatory response that develops most frequently in the genitourinary tract but has been reported at other sites. We report the case of 67-year-old man who presented with a lesion at the base of the tongue 7 months after chemoradiation for biopsy-proven invasive squamous cell carcinoma of the tongue. The lesion showed intense avidity by positron emission tomography and was biopsied with the putative clinical diagnosis of recurrent malignancy. Histologically, the lesion showed the characteristics of malacoplakia as well as abundant intracellular gram-negative bacilli. Ultrastructural analysis revealed giant lysosomes, intracytoplasmic calcific concretions (Michaelis-Gutman bodies), and partially digested gram-negative bacilli within vacuolated lysosomes of macrophages. To our knowledge, this is the seventh reported case of malacoplakia of the tongue and the first to develop at the site of prior radiation treatment of a carcinoma. The clinical features of this case, a review of previously reported cases, and a consideration of pathogenesis are presented. (C) 2012 Elsevier Inc. All rights reserved. C1 [Kradin, Richard L.; Nielsen, Petur; Selig, Martin; Hunt, Jennifer] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kradin, Richard L.; Nielsen, Petur; Selig, Martin; Hunt, Jennifer] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sheldon, Thomas A.] Concord Hosp, Payson Ctr Canc Care, Concord, NH 03301 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org NR 15 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1092-9134 J9 ANN DIAGN PATHOL JI Ann. Diagn. Pathol. PD JUN PY 2012 VL 16 IS 3 BP 214 EP 218 DI 10.1016/j.anndiagpath.2011.02.001 PG 5 WC Pathology SC Pathology GA 948GE UT WOS:000304490800009 PM 21530340 ER PT J AU Zaman, K Thurlimann, B Huober, J Schonenberger, A Pagani, O Luthi, J Simcock, M Giobbie-Hurder, A Berthod, G Genton, C Brauchli, P Aebi, S AF Zaman, K. Thuerlimann, B. Huober, J. Schoenenberger, A. Pagani, O. Luethi, J. Simcock, M. Giobbie-Hurder, A. Berthod, G. Genton, C. Brauchli, P. Aebi, S. CA Swiss Grp Clinical Canc Res SAKK TI Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07) SO ANNALS OF ONCOLOGY LA English DT Article DE aromatase inhibitors; BIG 1-98; bone; breast cancer; endocrine therapy; tamoxifen ID QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITOR; RANDOMIZED-TRIAL; ANASTROZOLE; FRACTURES; OSTEOPOROSIS; COMBINATION; EXEMESTANE; THERAPY AB Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy. C1 [Zaman, K.; Berthod, G.] Univ Hosp, CePO, Breast Ctr, Lausanne, Switzerland. [Thuerlimann, B.; Huober, J.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Schoenenberger, A.] Kantonsspital, Dept Oncol, Aarau, Switzerland. [Pagani, O.] Osped Italiano, Oncol Inst So Switzerland, Lugano, Switzerland. [Luethi, J.] Hosp Thun, Dept Oncol, Bern, Switzerland. [Simcock, M.; Genton, C.; Brauchli, P.] SAKK Coordinating Ctr, Bern, Switzerland. [Giobbie-Hurder, A.] Dana Farber Canc Inst, Ctr Stat, Int Breast Canc Study Grp, Boston, MA 02115 USA. [Aebi, S.] Univ Hosp, Div Med Oncol, Bern, Switzerland. RP Zaman, K (reprint author), Univ Hosp CHUV, Multidisciplinary Ctr Oncol, 46 Rue Bugnon, CH-1011 Lausanne, Switzerland. EM Khalil.Zaman@chuv.ch RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU State Secretariat for Education and Research (SER); Novartis Switzerland; Novartis FX State Secretariat for Education and Research (SER); Novartis Switzerland.; The following authors have declared conflict of interest-BT: stock of Novartis, travel grant for educational activities from Novartis, and honorarium from Astrazeneca for educational activities; JH: advisory relationship with Novartis and Astrazeneca and honorarium from Novartis and Astrazeneca. The following authors have declared no conflict of interest: KZ, AS, OP, JL, MS, AG-H, GB, CG, PB, and SA. NR 39 TC 11 Z9 11 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2012 VL 23 IS 6 BP 1474 EP + DI 10.1093/annonc/mdr448 PG 8 WC Oncology SC Oncology GA 948WO UT WOS:000304534000016 PM 22003243 ER PT J AU Heng, DY MacKenzie, MJ Vaishampayan, UN Bjarnason, GA Knox, JJ Tan, MH Wood, L Wang, Y Kollmannsberger, C North, S Donskov, F Rini, BI Choueiri, TK AF Heng, D. Y. MacKenzie, M. J. Vaishampayan, U. N. Bjarnason, G. A. Knox, J. J. Tan, M. H. Wood, L. Wang, Y. Kollmannsberger, C. North, S. Donskov, F. Rini, B. I. Choueiri, T. K. TI Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy SO ANNALS OF ONCOLOGY LA English DT Article DE primary refractory; renal cell carcinoma; VEGF; mTOR ID PHASE-III TRIAL; DOUBLE-BLIND; SORAFENIB; SUNITINIB AB Background: A subset of patients treated with initial anti-vascular endothelial growth factor (VEGF) therapy exhibit progressive disease (PD) as the best response per RECIST criteria. Methods: Data from patients with metastatic renal cell carcinoma (mRCC) treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Results: One thousand and fifty-six assessable patients received initial VEGF inhibitors and 272 (26%) of these patients had PD as best response. Initial treatment included sunitinib (n = 203), sorafenib (n = 51), or bevacizumab (n = 18). Six percent of patients were at favorable risk, 55% at intermediate risk, and 39% at poor risk. On multivariable analysis, predictors of PD were Karnofsky performance status < 80% [odds ratio (OR) = 2.3, P < 0.0001], diagnosis to treatment < 1 year (OR = 2.1, P < 0.0001), neutrophilia (OR = 1.9, P = 0.0021), thrombocytosis (OR = 1.7, P = 0.0068), and anemia (OR = 1.6, P = 0.0058). Median progression-free survival (PFS) in patients with PD versus without PD was 2.4 versus 11 months (P < 0.0001) and overall survival (OS) was 6.8 versus 29 months (P < 0.0001), respectively. One hundred and eight (40%) VEGF-refractory patients proceeded to receive further systemic therapies. Response rate, PFS, and OS for subsequent therapy were 9%, 2.5 months, and 7.4 months, respectively, with no statistical differences between patients who received VEGF versus mammalian target of rapamycin (mTOR) inhibitors. Conclusions: Primary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR and anti-VEGF agents produce similar outcomes. C1 [Heng, D. Y.; Wang, Y.] Univ Calgary, Dept Med Oncol, Tom Baker Canc Ctr, Alberta Hlth Serv Canc Care, Calgary, AB T2N 4N2, Canada. [MacKenzie, M. J.] London Reg Hlth Sci Ctr, Dept Oncol, London, ON, Canada. [Vaishampayan, U. N.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Bjarnason, G. A.] Sunnybrook Odette Canc Ctr, Dept Oncol, Toronto, ON, Canada. [Knox, J. J.] Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. [Tan, M. H.] Natl Canc Ctr, Inst Bioengn & Nanotechnol, Dept Oncol, Singapore, Singapore. [Wood, L.] Queen Elizabeth 2 Hlth Sci Ctr, Dept Oncol, Halifax, NS, Canada. [Kollmannsberger, C.] BC Canc Agcy, Dept Oncol, Vancouver, BC, Canada. [North, S.] Univ Alberta, Dept Oncol, Alberta Hlth Serv Canc Care, Cross Canc Inst, Edmonton, AB, Canada. [Donskov, F.] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Rini, B. I.] Cleveland Clin Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH USA. [Choueiri, T. K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, T. K.] Harvard Univ, Sch Med, Boston, MA USA. RP Heng, DY (reprint author), Univ Calgary, Dept Med Oncol, Tom Baker Canc Ctr, Alberta Hlth Serv Canc Care, 1331-29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Pfizer; Novartis; Bayer FX DYH, JJK, GAB, CK, SN have received consulting honoraria from Pfizer and Novartis. JK, FD, GB, BR, TC have received research funding from Pfizer and Novartis. JK has received research funding from Bayer. This project received no direct or indirect industry or pharmaceutical company funding. The other authors declare no conflicts of interest. NR 20 TC 52 Z9 55 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2012 VL 23 IS 6 BP 1549 EP + DI 10.1093/annonc/mdr533 PG 7 WC Oncology SC Oncology GA 948WO UT WOS:000304534000028 PM 22056973 ER PT J AU Said, SM Ashikhmina, E Greason, KL Suri, RM Park, SJ Daly, RC Burkhart, HM Dearani, JA Sundt, TM Schaff, HV AF Said, Sameh M. Ashikhmina, Elena Greason, Kevin L. Suri, Rakesh M. Park, Soon J. Daly, Richard C. Burkhart, Harold M. Dearani, Joseph A. Sundt, Thoralf M., III Schaff, Hartzell V. TI Do Pericardial Bioprostheses Improve Outcome of Elderly Patients Undergoing Aortic Valve Replacement? SO ANNALS OF THORACIC SURGERY LA English DT Article ID PORCINE; BOVINE; DURABILITY; PERIMOUNT; SIZE AB Background. Pericardial bioprostheses have favorable echocardiographic hemodynamics in the aortic position compared with porcine valves; however, there are few data comparing clinical outcomes. Our objective was to assess the late results of the two valve types. Methods. We reviewed 2,979 patients aged 65 years or older undergoing aortic valve replacement with pericardial (n = 1,976) or porcine (n = 1,003) prostheses between January 1993 and December 2007. The most common pericardial prostheses were Carpentier-Edwards Perimount and Mitroflow, and the most common porcine valves were Medtronic Mosaic, Carpentier-Edwards, Hancock modified orifice, and St. Jude Biocor. Follow-up extended to a maximum of 16 years (mean, 5.2 +/- 3.5 years). Results. Survival at 5, 10 and 12 years was, respectively, 68%, 33%, and 21% overall, was 68%, 30%, and 16% for patients with pericardial bioprosthesis, and was 69%, 38% and 27% for the porcine group. In a multivariate model, long-term survival was reduced in patients with diabetes, renal failure, prior myocardial infarction, congestive heart failure, and older age, but late survival was not higher in the pericardial valve group. Overall freedom from reoperation was 96%, 92%, and 90% at 5, 10, and 12 years, and freedom from explant was 98%, 96%, and 94% during the same period. The reason for explant was structural valve deterioration in 50 patients (2%). Conclusions. Despite the better hemodynamic performance documented in prior investigations, pericardial valves do not confer any survival advantage over porcine valves in patients aged 65 years or older undergoing aortic valve replacement. (Ann Thorac Surg 2012;93:1868-75) (C) 2012 by The Society of Thoracic Surgeons C1 [Said, Sameh M.] Mayo Clin, Div Cardiovasc Surg, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Anesthesia, Boston, MA 02115 USA. RP Said, SM (reprint author), Mayo Clin, Div Cardiovasc Surg, 200 1st St SW, Rochester, MN 55905 USA. EM schaft@mayo.edu OI Schaff, Hartzell/0000-0003-0994-027X NR 17 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2012 VL 93 IS 6 BP 1868 EP 1875 DI 10.1016/j.athoracsur.2012.01.061 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 947VG UT WOS:000304460000026 PM 22440366 ER PT J AU Cervera, R Bakaeen, FG Cornwell, LD Wang, XL Coselli, JS LeMaire, SA Chu, D AF Cervera, Roberto Bakaeen, Faisal G. Cornwell, Lorraine D. Wang, Xing Li Coselli, Joseph S. LeMaire, Scott A. Chu, Danny TI Impact of Functional Status on Survival After Coronary Artery Bypass Grafting in a Veteran Population SO ANNALS OF THORACIC SURGERY LA English DT Article ID AORTIC-VALVE-REPLACEMENT; HIGH-RISK PATIENTS; CARDIAC-SURGERY; LATE MORTALITY; FRAILTY; OLDER; OUTCOMES; AGE; DISEASE; INDEX AB Background. Although functional impairment has been shown to be an adverse outcome of frailty, little is known of its effect on patients after cardiac operations. We aimed to assess the effect of limited functional status on long-term survival after coronary artery bypass grafting (CABG). Methods. We reviewed prospectively gathered data from 1,503 consecutive patients who underwent isolated CABG between 1997 and 2009. We compared the outcomes of 318 patients with limited functional status and 1,185 patients without any functional impairment. The mean follow-up period was 65 months (range, 1 to 157 months). We assessed the relationship between functional status impairment and long-term survival by Cox regression analysis adjusted for confounding factors. Results. Functionally impaired patients were slightly older (63 +/- 9 vs 62 +/- 8 years, p = 0.05) and had more risk factors for adverse outcomes than patients who were functionally unimpaired. After adjustment for potential confounding variables by multivariate logistic regression analysis, preoperative limited functional status was not an independent predictor (odds ratio [95% confidence interval]) of 30-day mortality (1.4 [0.3 to 5.8], p = 0.67) or major adverse cardiac events (1.3 [0.5 to 3.3], p = 0.71), nor was it predictive of reduced long-term survival (10-year hazard ratio 1.0 [0.7 to 1.4], p = 0.85). Conclusions. Limited functional status was not an independent risk factor for early postoperative complications or death. Long-term survival in patients whose functional status was impaired before they underwent CABG was similar to that of patients who were functionally independent. C1 [Chu, Danny] Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Surg, Houston, TX USA. RP Chu, D (reprint author), Baylor Coll Med, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchu@bcm.edu NR 21 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2012 VL 93 IS 6 BP 1950 EP 1955 DI 10.1016/j.athoracsur.2012.02.071 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 947VG UT WOS:000304460000038 PM 22560262 ER PT J AU Carrick, R Ge, L Lee, LC Zhang, ZH Mishra, R Axel, L Guccione, JM Grossi, EA Ratcliffe, MB AF Carrick, Richard Ge, Liang Lee, Lik Chuan Zhang, Zhihong Mishra, Rakesh Axel, Leon Guccione, Julius M. Grossi, Eugene A. Ratcliffe, Mark B. TI Patient-Specific Finite Element-Based Analysis of Ventricular Myofiber Stress After Coapsys: Importance of Residual Stress SO ANNALS OF THORACIC SURGERY LA English DT Article ID ISCHEMIC MITRAL REGURGITATION; VOLUME REDUCTION SURGERY; DILATED CARDIOMYOPATHY; PAPILLARY-MUSCLE; REPAIR TECHNIQUE; ANNULOPLASTY; VALVE; MODEL AB Background. We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc, Maple Grove, MN) implantation using a finite element model of the left ventricle (LV). Chronic ischemic mitral regurgitation is caused by LV remodeling after posterolateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases chronic ischemic mitral regurgitation. Methods. Finite element models of the LV were based on magnetic resonance images obtained before (preoperatively) and after (postoperatively) coronary artery bypass grafting with Coapsys implantation in a single patient. To determine the effect of Coapsys and LV before stress, virtual Coapsys was performed on the preoperative model. Diastolic and systolic material variables in the preoperative, postoperative, and virtual Coapsys models were adjusted so that model LV volume agreed with magnetic resonance imaging data. Chronic ischemic mitral regurgitation was abolished in the postoperative models. In each case, myofiber stress and pump function were calculated. Results. Both postoperative and virtual Coapsys models shifted end-systolic and end-diastolic pressure-volume relationships to the left. As a consequence and because chronic ischemic mitral regurgitation was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at end-diastole and end-systole in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV prestress was necessary for accurate calculation of LV myofiber stress, especially in the remote zone. Conclusions. Coapsys decreases myofiber stress at end-diastole and end-systole. The improvement in myofiber stress may contribute to the long-term effect of Coapsys on LV remodeling. C1 Univ Vermont, Coll Med, Burlington, VT USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. NYU, Dept Cardiothorac Surg, New York, NY USA. NYU, Dept Radiol, New York, NY 10016 USA. New York Harbor Vet Affairs Med Ctr, New York, NY USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratclifte@va.gov OI GROSSI, eugene/0000-0002-2066-7035; Axel, Leon/0000-0003-0608-4690 FU NIH [R01-HL084431, R01-HL077921, R01-HL086400]; University of Vermont FX This study was supported by NIH grants R01-HL084431 (M.B.R.), R01-HL077921 (J.M.G.), and R01-HL086400 (J.M.G.). RC. was supported by a Summer Research Fellowship from the University of Vermont. This support is gratefully acknowledged. NR 30 TC 14 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2012 VL 93 IS 6 BP 1964 EP 1971 DI 10.1016/j.athoracsur.2012.03.001 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 947VG UT WOS:000304460000040 PM 22560323 ER PT J AU Jernigan, MG Press, EG Nguyen, MH Clancy, CJ Shields, RK AF Jernigan, Meredith G. Press, Ellen G. Nguyen, M. Hong Clancy, Cornelius J. Shields, Ryan K. TI The Combination of Doripenem and Colistin Is Bactericidal and Synergistic against Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RISK-FACTORS; INFECTION; OUTCOMES; PHARMACOKINETICS; ACQUISITION; PREDICTORS; MORTALITY; IMPACT AB We tested two-drug combinations of doripenem, colistin, gentamicin, and doxycycline against 12 carbapenemase-producing Klebsiella pneumoniae (KPC) isolates by time-kill. The combination of doripenem and colistin reduced the starting inocula by 2 logs for each isolate (range, 2.02 to 6.01 log(10)) and was bactericidal and synergistic against 75 and 50%, respectively. Among colistin- and pan-drug-resistant isolates, synergy was identified in 60 and 67%, respectively. All other combinations were inferior. We are currently evaluating the combination of doripenem and colistin as a frontline therapy for KPC infection. C1 [Press, Ellen G.; Nguyen, M. Hong; Clancy, Cornelius J.; Shields, Ryan K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Jernigan, Meredith G.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM cjc76@pitt.edu FU National Center for Research Resources [KL2 RR024154] FX The project described was supported by award number KL2 RR024154 from the National Center for Research Resources to R.K.S. NR 24 TC 37 Z9 43 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2012 VL 56 IS 6 BP 3395 EP 3398 DI 10.1128/AAC.06364-11 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 947LZ UT WOS:000304432800082 PM 22430958 ER PT J AU Roemer, FW Kwoh, CK Hannon, MJ Green, SM Jakicic, JM Boudreau, R Crema, MD Moore, CE Guermazi, A AF Roemer, Frank W. Kwoh, C. Kent Hannon, Michael J. Green, Stephanie M. Jakicic, John M. Boudreau, Robert Crema, Michel D. Moore, Carolyn E. Guermazi, Ali TI Risk factors for magnetic resonance imaging-detected patellofemoral and tibiofemoral cartilage loss during a six-month period: The Joints On Glucosamine study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYMPTOMATIC KNEE OSTEOARTHRITIS; RADIOGRAPHIC OSTEOARTHRITIS; DISEASE PROGRESSION; MULTICENTER OSTEOARTHRITIS; MENISCAL EXTRUSION; NATURAL-HISTORY; ASSOCIATION; FRAMINGHAM; SYNOVITIS; VOLUME AB Objective To assess several baseline risk factors that may predict patellofemoral and tibiofemoral cartilage loss during a 6-month period. Methods For 177 subjects with chronic knee pain, 3T magnetic resonance imaging (MRI) of both knees was performed at baseline and followup. Knees were semiquantitatively assessed, evaluating cartilage morphology, subchondral bone marrow lesions, meniscal morphology/extrusion, synovitis, and effusion. Age, sex, and body mass index (BMI), bone marrow lesions, meniscal damage/extrusion, synovitis, effusion, and prevalent cartilage damage in the same subregion were evaluated as possible risk factors for cartilage loss. Logistic regression models were applied to predict cartilage loss. Models were adjusted for age, sex, treatment, and BMI. Results Seventy-nine subregions (1.6%) showed incident or worsening cartilage damage at followup. None of the demographic risk factors was predictive of future cartilage loss. Predictors of patellofemoral cartilage loss were effusion, with an adjusted odds ratio (OR) of 3.5 (95% confidence interval [95% CI] 1.39.4), and prevalent cartilage damage in the same subregion with an adjusted OR of 4.3 (95% CI 1.314.1). Risk factors for tibiofemoral cartilage loss were baseline meniscal extrusion (adjusted OR 3.6 [95% CI 1.310.1]), prevalent bone marrow lesions (adjusted OR 4.7 [95% CI 1.119.5]), and prevalent cartilage damage (adjusted OR 15.3 [95% CI 4.947.4]). Conclusion Cartilage loss over 6 months is rare, but may be detected semiquantitatively by 3T MRI and is most commonly observed in knees with Kellgren/Lawrence grade 3. Predictors of patellofemoral cartilage loss were effusion and prevalent cartilage damage in the same subregion. Predictors of tibiofemoral cartilage loss were prevalent cartilage damage, bone marrow lesions, and meniscal extrusion. C1 [Roemer, Frank W.] Boston Univ, Med Ctr, Dept Radiol, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Roemer, Frank W.] Klinikum Augsburg, Augsburg, Germany. [Kwoh, C. Kent; Hannon, Michael J.; Green, Stephanie M.; Jakicic, John M.; Boudreau, Robert] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Crema, Michel D.] Inst Diagnost Imaging, Ribeirao Preto, Brazil. [Crema, Michel D.] Univ Sao Paulo, BR-14049 Ribeirao Preto, Brazil. [Moore, Carolyn E.] Texas Womans Univ, Houston, TX USA. RP Roemer, FW (reprint author), Boston Univ, Med Ctr, Dept Radiol, Quantitat Imaging Ctr, FGH Bldg,3rd Floor,820 Harrison Ave, Boston, MA 02118 USA. EM froemer@bu.edu OI Boudreau, Robert/0000-0003-0162-5187 FU Beverage Institute for Health & Wellness, the Coca Cola Company; Multidisciplinary Clinical Research Center for Musculoskeletal and Skin Diseases at the University of Pittsburgh (NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases) [P60]; Beverage Institute for Health Wellness; Jenny Craig; Alere Wellbeing; Facet Solutions; Genzyme; Stryker; Merck Serono; AstraZeneca; General Electric Healthcare FX The Joints On Glucosamine study is funded by a grant from the Beverage Institute for Health & Wellness, the Coca Cola Company. The statistical analysis was partially supported by the Multidisciplinary Clinical Research Center for Musculoskeletal and Skin Diseases at the University of Pittsburgh (NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases P60 grant).; Drs. Roemer and Guermazi own stock or stock options in Boston Imaging Core Lab; Dr. Roemer is vice president and Dr. Guermazi is president of Boston Imaging Core Lab. Dr. Kwoh has received a research grant from the Beverage Institute for Health & Wellness. Dr. Jakicic has received consulting fees, speaking fees, and/or honoraria from Jenny Craig and Alere Wellbeing (less than $10,000 each). Dr. Crema owns stock or stock options in Boston Imaging Core Lab. Dr. Guermazi has received consulting fees, speaking fees, and/or honoraria from Facet Solutions, Genzyme, and Stryker (less than $10,000 each) and from Merck Serono and AstraZeneca (more than $10,000 each) and has received a research grant from General Electric Healthcare. NR 51 TC 29 Z9 29 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 2012 VL 64 IS 6 BP 1888 EP 1898 DI 10.1002/art.34353 PG 11 WC Rheumatology SC Rheumatology GA 948SE UT WOS:000304522100022 PM 22213129 ER PT J AU Washington, S Caughey, AB Cheng, YW Bryant, AS AF Washington, Sierra Caughey, Aaron B. Cheng, Yvonne W. Bryant, Allison S. TI Racial and Ethnic Differences in Indication for Primary Cesarean Delivery at Term: Experience at One U.S. Institution SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article DE cesarean delivery; disparity; race and ethnicity ID HEALTH-CARE BENEFICIARIES; US MILITARY HOSPITALS; BREECH PRESENTATION; SECTION DELIVERY; RATES; RISK; RACE; POPULATION; CALIFORNIA; PREMIUMS AB Background Black and Latina women in the United States are known to undergo cesarean delivery at a higher rate than other women. We sought to explore the role of medical indications for cesarean delivery as a potential explanation for these differences. Methods A retrospective cohort study was conducted of 11,034 primiparas delivering at term at the University of California, San Francisco, between 1990 and 2008. We used multivariable analyses to evaluate racial and ethnic differences in risks of, and indications for, cesarean delivery. Results The overall rate of cesarean delivery in our cohort was 21.9 percent. Black and Latina women were at significantly higher odds of undergoing cesarean delivery than white women (adjusted odds ratio or AOR: 1.54; 95% CI: 1.30, 1.83, and 1.21; 95% CI: 1.03, 1.43, respectively). Black women were at significantly higher odds of undergoing cesarean delivery for nonreassuring fetal heart tracings than white women (AOR: 2.19; 95% CI: 1.55, 3.09), and black women (AOR: 1.55; 95% CI: 1.21, 1.98), Latina women (AOR: 1.48; 95% CI: 1.19, 1.85), and Asian women (AOR: 1.47; 95% CI: 1.22, 1.85) were at significantly higher odds of undergoing cesarean delivery for failure to progress. Black, Latina, and Asian women were at significantly lower odds of undergoing cesarean delivery for malpresentation than white women (AOR: 0.56; 95% CI: 0.34, 0.89, 0.66; 95% CI: 0.44, 0.98, and 0.55; 95% CI: 0.40, 0.76, respectively). Conclusions Racial and ethnic differences exist in specific indications for cesarean delivery among primiparas. Clarifying the possible reasons for increased cesareans for nonreassuring fetal heart tracing in black women, in particular, may help to decrease excess cesarean deliveries in this racial and ethnic group. (BIRTH 39:2 June 2012) C1 [Washington, Sierra; Caughey, Aaron B.; Cheng, Yvonne W.; Bryant, Allison S.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Cheng, Yvonne W.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Bryant, Allison S.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Washington, Sierra] Indiana Univ, Dept Obstet & Gynecol, Indianapolis, IN USA. RP Bryant, AS (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St,Founders 4, Boston, MA 02114 USA. FU National Institutes of Health (NIH/NCRR/OD UCSF-CTSI), Washington, DC [KL2 RR024130]; Robert Wood Johnson Foundation, Princeton, New Jersey, United States of America [RWJF-63524, RWJF-61535] FX Funding for this publication was supported by grants from the National Institutes of Health (NIH/NCRR/OD UCSF-CTSI Grant No. KL2 RR024130), Washington, DC, and from the Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation (Grant No. RWJF-63524), Princeton, New Jersey, United States of America, to Dr Allison Bryant. Dr Aaron Caughey is supported by the Robert Wood Johnson Foundation as a Physician Faculty Scholar (Grant No. RWJF-61535), Princeton, New Jersey, United States of America. NR 37 TC 15 Z9 15 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD JUN PY 2012 VL 39 IS 2 BP 128 EP 134 PG 7 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 949SY UT WOS:000304597400006 PM 23281861 ER PT J AU Wu, AHB Lorizio, W Tchu, S Lynch, K Gerona, R Ji, WY Ruan, WM Ruddy, KJ Desantis, SD Burstein, HJ Ziv, E AF Wu, Alan H. B. Lorizio, Wendy Tchu, Simone Lynch, Kara Gerona, Roy Ji, Wuyang Ruan, Weiming Ruddy, Kathryn J. Desantis, Stephen D. Burstein, Harold J. Ziv, Elad TI Estimation of tamoxifen metabolite concentrations in the blood of breast cancer patients through CYP2D6 genotype activity score SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Tamoxifen; Endoxifen; Genotype; Activity score; CYP2D6 ID THERAPY; WOMEN; PHARMACOGENOMICS; POLYMORPHISMS; PERFORMANCE; EXPOSURE; OUTCOMES; IMPACT AB Tamoxifen, a prodrug used for adjuvant breast cancer therapy, requires conversion to the active metabolite endoxifen through CYP 2D6. We aimed to construct an algorithm to predict endoxifen concentrations based on a patient's CYP 2D6 genotype, demographic factors, and co-medication use. Eighty-eight women enrolled in the UCSF TamGen II study and 81 women enrolled in a prospective study at Dana-Farber Cancer Institute were included in this analysis. All the women had been on tamoxifen for at least 3 months before blood collection. Demographic information included the patient's age, race/ethnicity, body mass index (where available), and self-reported and measured medications and herbals that affect 2D6 activity. DNA was extracted and genotyped for 2D6 (Amplichip, Roche Diagnostics). An activity score was calculated based on genotypes and adjusted for use of medications known to inhibit 2D6. Serum was tested for tamoxifen and metabolite concentrations and for the presence of drugs by liquid chromatography/mass spectrometry. Univariate and multivariate regression analysis were computed for age, body mass index, ethnicity, and adjusted activity score to predict tamoxifen metabolite concentrations in the training data-set of UCSF patients, and the resulting algorithm was validated in the Dana-Farber patients. For the training set, the correlation coefficient (r (2)) for log endoxifen and N-desmethyltamoxifen:endoxifen ratio to activity score, age, and race, were 0.520 and 0.659, respectively; 0.324 and 0.567 for the validation; and 0.396 and 0.615 for both the datasets combined. An algorithm that incorporates genotype and demographic variables can be used to predict endoxifen concentrations for women on tamoxifen therapy. If endoxifen levels are confirmed to be predictive of tamoxifen benefit, then this algorithm may be helpful to determine which women warrant endoxifen testing. C1 [Wu, Alan H. B.; Tchu, Simone; Lynch, Kara; Gerona, Roy; Ji, Wuyang; Ruan, Weiming] San Francisco Gen Hosp, Dept Lab Med, San Francisco, CA 94110 USA. [Lorizio, Wendy; Ziv, Elad] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Ruddy, Kathryn J.; Desantis, Stephen D.; Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wu, AHB (reprint author), San Francisco Gen Hosp, Dept Lab Med, 1001 Potrero Ave,Room 2M27, San Francisco, CA 94110 USA. EM wualan@labmed2.ucsf.edu; wlorizio@medicine.ucsf.edu; Simone.Tchu@ucsf.edu; kara.lynch@ucsf.edu; Roy.Gerona@ucsf.edu; jiwuyang5@gmail.com; weiming0603@gmail.com; kruddy@partners.org; Stephen_Desantis@dfci.harvard.edu; hal_burstein@dfci.harvard.edu; elad.ziv@ucsf.edu RI Ziv, Elad/L-5396-2014 FU NCI NIH HHS [R01 CA120120] NR 23 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2012 VL 133 IS 2 BP 677 EP 683 DI 10.1007/s10549-012-1963-2 PG 7 WC Oncology SC Oncology GA 949XJ UT WOS:000304610600026 PM 22294487 ER PT J AU Metcalfe, KA Mian, N Enmore, M Poll, A Llacuachaqui, M Nanda, S Sun, P Hughes, KS Narod, SA AF Metcalfe, Kelly A. Mian, Nida Enmore, Melissa Poll, Aletta Llacuachaqui, Marcia Nanda, Sonia Sun, Ping Hughes, Kevin S. Narod, Steven A. TI Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BRCA2; Breast cancer Genetic testing; Jewish ID HEREDITARY BREAST-CANCER; PROPHYLACTIC SURGERY; FOUNDER MUTATIONS; OVARIAN-CANCER; INCREASED RISK; EVENT SCALE; IMPACT; DISTRESS; CARRIERS; SURVEILLANCE AB There are two mutations in BRCA1 and one in BRCA2, which are present in up to 2.5% of Jewish women. Population genetic testing for Jewish women has been proposed; however, it is unclear how this would impact the uptake of cancer prevention options and psychosocial functioning in women with a positive result. Two thousand and eighty unselected Jewish women were tested for the Jewish BRCA mutations, and 1.1% were positive. Cancer-related distress was measured before testing, and at 1 and 2 years post-testing. Information on uptake of cancer risk reduction options was collected at 2 years. Breast and ovarian cancer risks were estimated using BRCAPRO. Within 2 years of receiving a positive result, 11.1% of women had prophylactic mastectomy, and 89.5% had a prophylactic oophorectomy. The mean breast cancer risk was estimated to be 37.2% at time of testing, compared to 20.9% at 2 years post-testing. The mean ovarian cancer risk was estimated to be 24.5% at time of testing, compared to 7.5% at 2 years following testing. Distress decreased between 1 and 2 years for women with prophylactic mastectomy and oophorectomy (P = 0.02), and for women with prophylactic oophorectomy only (P = 0.04) but not for those with neither surgery. The majority of Jewish women with a BRCA mutation identified through a population screening elected prophylactic oophorectomy, but a few had a prophylactic mastectomy. Uptake of either surgery resulted in decreased distress. Provision of population BRCA testing resulted in reduced risks of breast and ovarian cancers in women with a mutation. C1 [Metcalfe, Kelly A.; Mian, Nida; Enmore, Melissa; Poll, Aletta; Llacuachaqui, Marcia; Nanda, Sonia; Sun, Ping; Narod, Steven A.] Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada. [Metcalfe, Kelly A.] Univ Toronto, Lawrence S Bloomberg Fac Nursing, Toronto, ON, Canada. [Hughes, Kevin S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Narod, Steven A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Narod, SA (reprint author), Womens Coll Res Inst, 790 Bay St, Toronto, ON M5G 1N8, Canada. EM Steven.narod@wchospital.ca OI Hughes, Kevin/0000-0003-4084-6484 NR 23 TC 23 Z9 23 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2012 VL 133 IS 2 BP 735 EP 740 DI 10.1007/s10549-011-1941-0 PG 6 WC Oncology SC Oncology GA 949XJ UT WOS:000304610600032 PM 22240989 ER PT J AU Kimball, AB AF Kimball, A. B. TI A new era in skin care: the omics revolution SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material C1 [Kimball, A. B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 7 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUN PY 2012 VL 166 SU 2 SI SI DI 10.1111/j.1365-2133.2012.10858.x PG 2 WC Dermatology SC Dermatology GA 953VJ UT WOS:000304901000001 ER PT J AU Reardon, DA Conrad, CA Cloughesy, T Prados, MD Friedman, HS Aldape, KD Mischel, P Xia, J DiLea, C Huang, J Mietlowski, W Dugan, M Chen, W Yung, WKA AF Reardon, David A. Conrad, Charles A. Cloughesy, Timothy Prados, Michael D. Friedman, Henry S. Aldape, Kenneth D. Mischel, Paul Xia, Jane DiLea, CliVord Huang, Jerry Mietlowski, William Dugan, Margaret Chen, Wei Yung, W. K. Alfred TI Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Glioblastoma; Tyrosine kinase inhibitor; Epidermal growth factor receptor; Vascular endothelial growth factor receptor; RAD001 ID EPIDERMAL-GROWTH-FACTOR; BEVACIZUMAB PLUS IRINOTECAN; CONFERS ENHANCED TUMORIGENICITY; NUDE-MOUSE MODEL; MALIGNANT GLIOMA; TARGETED THERAPY; REDUCES GROWTH; BRAIN-TUMORS; TRIAL; EXPRESSION AB Vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) play a significant role in glioblastoma angiogenesis and proliferation, making tyrosine kinase (TK) receptors logical targets for treatment. We evaluated AEE788, a reversible TK inhibitor that inhibits EGFR and VEGFR, in recurrent glioblastoma patients. In this dose-escalation, phase I study, patients with recurrent glioblastoma received AEE788 once daily in 28-day cycles in stratified subgroups: those receiving (1) non-enzyme-inducing anticonvulsants drugs or no anticonvulsants (Group A) and (2) enzyme-inducing anticonvulsant drugs (Group B). A dose-expansion phase stratified patients by surgical eligibility. Primary objectives were to determine dose-limiting toxicity (DLT) and maximum tolerated dose; secondary objectives included evaluating (1) safety/tolerability, (2) pharmacokinetics, and (3) preliminary antitumor activity. Sixty-four glioblastoma patients were enrolled. Two Group A patients experienced DLTs (proteinuria and stomatitis) at 550 mg; 550 mg was, therefore, the highest dose evaluated and dose limiting. One Group B patient receiving 800 mg experienced a DLT (diarrhea). The initially recommended dose for dose-expansion phase for Group A was 400 mg; additional patients received 250 mg to assess the hepatotoxicity. Most frequently reported adverse events (AEs) included diarrhea and rash. Serious AEs, most commonly grade 3/4 liver function test elevations, were responsible for treatment discontinuation in 17% of patients. AEE788 concentrations were reduced by EIACD. The best overall response was stable disease (17%). Continuous, once-daily AEE788 was associated with unacceptable toxicity and minimal activity for the treatment of recurrent glioblastoma. The study was, therefore, discontinued prematurely. C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Conrad, Charles A.; Aldape, Kenneth D.; Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cloughesy, Timothy; Mischel, Paul; Chen, Wei] Univ Calif Los Angeles, Los Angeles, CA USA. [Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Friedman, Henry S.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Xia, Jane; DiLea, CliVord; Huang, Jerry; Mietlowski, William; Dugan, Margaret] Novartis Pharmaceut, E Hanover, NJ USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 460F, Boston, MA 02215 USA. EM David_Reardon@DFCI.harvard.edu FU NCATS NIH HHS [UL1 TR000124] NR 45 TC 22 Z9 22 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 2012 VL 69 IS 6 BP 1507 EP 1518 DI 10.1007/s00280-012-1854-6 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 950BB UT WOS:000304622600013 PM 22392572 ER PT J AU De Costa, AMA Schuyler, CA Walker, DD Young, MRI AF De Costa, Anna-Maria A. Schuyler, Corinne A. Walker, David D. Young, M. Rita I. TI Characterization of the evolution of immune phenotype during the development and progression of squamous cell carcinoma of the head and neck SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE HNSCC; Premalignant; Immunoediting; Th1/Tc1 cells; Th17 cells ID T-CELLS; PD-1 EXPRESSION; TH17 CELLS; CANCER; MODEL; DYSFUNCTION; MICE; INFLAMMATION; LYMPHOCYTES; INTERFERON AB While studies have indicated that squamous cell carcinoma of the head and neck (HNSCC) is associated with immune suppression, these studies did not analyze the immune response at the dysplastic stage. The present study utilized a mouse model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis to examine the alterations in immune phenotype at the premalignant and malignant stages of HNSCC. Cervical lymph nodes of HNSCC-bearing mice were found to contain a greater number of cells, including a greater number of conventional (Tconv) and regulatory (Treg) T cells, compared to cervical lymph nodes of control and premalignant lesion-bearing mice, though the Tconv cells appear to be less proliferative and the Treg cells appear to be less suppressive at the HNSCC stage. Premalignant lesion-bearing mouse lymph nodes consist of a greater percentage of Tconv cells expressing markers for activation, memory, and exhaustion compared to both control and HNSCC-bearing mice. Also, lymph nodes' cells from both premalignant lesion-bearing and HNSCC-bearing mice include increased levels of Th1, Tc1, and Th17 cells, with no differences in levels of Th2 cells, compared to control mice. The data show that while there is the expected increase in immunosuppressive Tregs in lymph nodes when HNSCC is present, there is also an unexpected increase in immune populations usually associated with a beneficial antitumor response, including Tconv cells and Th1 and Tc1 cells. In addition, the results demonstrate that the premalignant stage of HNSCC development is associated with a robust immune response involving an increase in inflammatory Th1, Tc1, and Th17 cells. C1 [De Costa, Anna-Maria A.; Schuyler, Corinne A.; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Walker, David D.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29401 USA. [De Costa, Anna-Maria A.; Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Medical Research Service of the Department of Veterans Affairs; National Institutes of Health [RO1 CA128837, RO1 DE018268] FX This work was supported by the Medical Research Service of the Department of Veterans Affairs and by grants RO1 CA128837 and RO1 DE018268 from the National Institutes of Health to MRIY. NR 37 TC 11 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JUN PY 2012 VL 61 IS 6 BP 927 EP 939 DI 10.1007/s00262-011-1154-8 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA 950AU UT WOS:000304621900017 PM 22116344 ER PT J AU Carrithers, MD AF Carrithers, Michael D. TI Current Immunotherapy of Multiple Sclerosis and Future Challenges: Relevance of Immune-Mediated Repair SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE Brain; demyelination; immune surveillance; innate immunity; interferon; lymphocyte; natalizumab ID PLACEBO-CONTROLLED TRIAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CENTRAL-NERVOUS-SYSTEM; CONTROLLED PHASE IIB; DOUBLE-BLIND; T-CELLS; GLATIRAMER ACETATE; INTERFERON-BETA; IN-VITRO; INTRAMUSCULAR INTERFERON AB Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system and can cause severe neurological disability. Current immune therapy with beta-interferons, glatiramer acetate, immune suppressives, or selective adhesion molecule inhibitors can reduce the frequency and severity of acute attacks in a majority of patients but have little effect on the progressive phase of the disease. Patients who require aggressive immune therapy are also at risk for the development of potentially fatal opportunistic infections. Here current and emerging immune therapy options are discussed, and immune-mediated strategies to preserve normal immune surveillance and mediate tissue repair are proposed. C1 [Carrithers, Michael D.] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Neurol Serv, Madison, WI USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Dept Neurol, 1300 Univ Ave, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu NR 96 TC 3 Z9 3 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD JUN PY 2012 VL 13 IS 8 BP 1409 EP 1417 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 949SQ UT WOS:000304596600005 PM 22339217 ER PT J AU Ibrahimi, OA Kilmer, SL AF Ibrahimi, Omar A. Kilmer, Suzanne L. TI Long-Term Clinical Evaluation of a 800-nm Long-Pulsed Diode Laser with a Large Spot Size and Vacuum-Assisted Suction for Hair Removal SO DERMATOLOGIC SURGERY LA English DT Article ID MODE RUBY-LASER; FOLLOW-UP; REDUCTION; ALEXANDRITE; DAMAGE; TRIAL; LIGHT; NM AB Background The long-pulsed diode (800810-nm) laser is one of the most commonly used and effective lasers for hair removal. Limitations of currently available devices include a small treatment spot size, treatment-associated pain, and the need for skin cooling. Objective To evaluate the long-term hair reduction capabilities of a long-pulsed diode laser with a large spot size and vacuum assisted suction. Methods Thirty-five subjects were enrolled in a prospective, self-controlled, single-center study of axillary hair removal. The study consisted of three treatments using a long-pulsed diode laser with a large spot size and vacuum-assisted suction at 4- to 6-week intervals with follow-up visits 6 and 15 months after the last treatment. Hair clearance was quantified using macro hair-count photographs taken at baseline and at 6- and 15-month follow-up visits. Changes in hair thickness and color, levels of treatment-associated pain, and adverse events were additional study endpoints. Results There was statistically significant hair clearance at the 6 (54%) and 15-month (42%) follow-up visits. Remaining hairs were thinner and lighter at the 15-month follow-up visit, and the majority of subjects reported feeling up to mild to moderate pain during treatment without the use of pretreatment anesthesia or skin cooling. Conclusions A long-pulsed diode laser with a large spot size and vacuum-assisted suction is safe and effective for long-term hair removal. This is the largest prospective study to evaluate long-term hair removal and the first to quantify decreases in hair thickness and darkness with treatment. C1 [Ibrahimi, Omar A.] Univ Connecticut, Ctr Hlth, Dept Dermatol, Farmington, CT 06032 USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Kilmer, Suzanne L.] Laser & Skin Surg Ctr No Calif, Sacramento, CA USA. RP Ibrahimi, OA (reprint author), Univ Connecticut, Ctr Hlth, Dept Dermatol, 21 South Rd,2nd Floor, Farmington, CT 06032 USA. EM omar.ibrahimi@gmail.com NR 16 TC 5 Z9 5 U1 0 U2 3 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 2012 VL 38 IS 6 BP 912 EP 917 DI 10.1111/j.1524-4725.2012.02380.x PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 948UK UT WOS:000304528100013 PM 22455549 ER PT J AU Barrett, LF AF Barrett, Lisa Feldman TI Emotions Are Real SO EMOTION LA English DT Article DE emotion; affect; social construction; conceptual acts ID BILATERAL AMYGDALA DAMAGE; DEEP BRAIN-STIMULATION; HUNTINGTONS-DISEASE; BASIC EMOTIONS; PREFRONTAL CORTEX; NATURAL KINDS; PSYCHOLOGICAL CONSTRUCTION; EXPRESSION RECOGNITION; HIPPOCAMPAL-FORMATION; IMPAIRED RECOGNITION AB It is obvious that emotions are real, but the question is what kind of "real" are they? In this article, I outline a theoretical approach where emotions are a part of social reality. I propose that physical changes (in the face, voice, and body, or neural circuits for behavioral adaptations like freezing, fleeing, or fighting) transform into an emotion when those changes take on psychological functions that they cannot perform by their physical nature alone. This requires socially shared conceptual knowledge that perceivers use to create meaning from these physical changes (as well as the circuitry that supports this meaning making). My claim is that emotions are, at the same time, socially constructed and biologically evident. Only when we understand all the elements that construct emotional episodes, in social, psychological, and biological terms, will we understand the nature of emotion. C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. EM l.barrett@neu.edu FU NIH HHS [DP1OD003312] NR 148 TC 66 Z9 67 U1 7 U2 56 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2012 VL 12 IS 3 BP 413 EP 429 DI 10.1037/a0027555 PG 17 WC Psychology, Experimental SC Psychology GA 948OO UT WOS:000304512700001 PM 22642358 ER PT J AU Campos, SM Dizon, DS AF Campos, Susana M. Dizon, Don S. TI Antimitotic Inhibitors SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Microtubule-targeting agents; Microtubule resistance; Epothilones; Eribulin; Cabazitaxel; Aurora kinase inhibitors; PLK inhibitors; KSP inhibitors ID METASTATIC BREAST-CANCER; ADVANCED SOLID TUMORS; RESISTANT PROSTATE-CANCER; MICROTUBULE-STABILIZING AGENTS; GYNECOLOGIC-ONCOLOGY-GROUP; PRIMARY PERITONEAL CANCER; PHASE-II TRIAL; IXABEPILONE PLUS CAPECITABINE; ALBUMIN-BOUND PACLITAXEL; TUBULIN-BINDING AGENTS AB Of the agents available in the treatment of both solid and hematologic cancers, microtubule-targeted agents are among the most widely used and exploiting other mechanisms involving the microtubule and its role in mitosis is an area of continued interest. This review will focus on novel microtubule-targeted agents, both recently approved (eg, ixabepilone and eribulin) and in later-stage clinical trials, and kinase inhibitors that aim to directly inhibit the mitotic spindle, such as the aurora kinase, pololike kinase, and kinsein-spindle protein inhibitors. C1 [Dizon, Don S.] Brown Univ, Warren Alpert Med Sch, Program Womens Oncol, Women & Infants Hosp, Providence, RI 02905 USA. [Campos, Susana M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Program Gynecol Oncol,Dept Med Oncol, Boston, MA 02215 USA. RP Dizon, DS (reprint author), Brown Univ, Warren Alpert Med Sch, Program Womens Oncol, Women & Infants Hosp, 101 Dudley St, Providence, RI 02905 USA. EM ddizon@wihri.org NR 143 TC 9 Z9 9 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 2012 VL 26 IS 3 BP 607 EP + DI 10.1016/j.hoc.2012.01.007 PG 24 WC Oncology; Hematology SC Oncology; Hematology GA 949JF UT WOS:000304571800009 PM 22520982 ER PT J AU Lee, W Nelson, R Akmal, Y Mailey, B McKenzie, S Artinyan, A Ashing-Giwa, KT Chen, YJ Garcia-Aguilar, J Kim, J AF Lee, Wendy Nelson, Rebecca Akmal, Yasir Mailey, Brian McKenzie, Shaun Artinyan, Avo Ashing-Giwa, Kimlin Tam Chen, Yi-Jen Garcia-Aguilar, Julio Kim, Joseph TI Racial and ethnic disparities in outcomes with radiation therapy for rectal adenocarcinoma SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE Rectal cancer; Radiation; Neoadjuvant; Disparities ID PATHOLOGICAL COMPLETE RESPONSE; COLORECTAL-CANCER TREATMENTS; PREOPERATIVE CHEMORADIATION; SOCIOECONOMIC-STATUS; PREDICTIVE FACTORS; ADJUVANT THERAPY; SURVIVAL; CHEMORADIOTHERAPY; RADIOTHERAPY; CAPECITABINE AB Race/ethnicity may modify cancer outcomes and manifest as survival disparities for patients with rectal cancer. Our objective was to determine whether disparate rectal cancer outcomes result from variable efficacy of radiation therapy for major racial/ethnic groups. The Los Angeles County Cancer Surveillance Program (CSP) identified patients with rectal adenocarcinoma between the years 1988 and 2006. Patients who underwent curative-intent surgery were grouped by race/ethnicity and by receipt (yes vs. no) and timing (neoadjuvant vs. adjuvant) of radiation therapy. The impact of receipt and timing of radiation therapy on overall survival was then assessed. Of 4,961 patients in CSP, 2,229 (45%) received radiation therapy. Overall, there was no difference in survival among patients according to receipt of radiation therapy. We then examined the radiation cohort, wherein 919 (41%) and 1,310 (59%) patients received neoadjuvant or adjuvant radiation, respectively. Overall, patients who received neoadjuvant compared to adjuvant radiation had improved survival (median survival (MS), 9.4 vs. 6.8 years, respectively; p < 0.001). Among those patients who received neoadjuvant radiation, whites, Hispanics, and Asians had significantly longer survival than blacks (MS, 10.4, 10.4, and 10.4 vs. 4.4 years, respectively; p = 0.003). On multivariate analysis, race/ethnicity was an independent predictor of survival (p = 0.001). To our knowledge, this is the first study examining the efficacy of radiation therapy for racial/ethnic groups with rectal cancer. Disparate outcomes were observed for the administration of radiation therapy for select racial/ethnic groups. The reasons for these disparities in outcomes should be investigated to better optimize radiation therapy for patients with rectal cancer. C1 [Lee, Wendy; Akmal, Yasir; Mailey, Brian; Garcia-Aguilar, Julio; Kim, Joseph] City Hope Comprehens Canc Ctr, Dept Surg, Duarte, CA 91010 USA. [Nelson, Rebecca] City Hope Comprehens Canc Ctr, Dept Biostat, Duarte, CA 91010 USA. [McKenzie, Shaun] Univ Kentucky, Sch Med, Dept Surg, Lexington, KY 40536 USA. [Ashing-Giwa, Kimlin Tam] City Hope Comprehens Canc Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Chen, Yi-Jen] City Hope Comprehens Canc Ctr, Dept Radiat Oncol, Duarte, CA 91010 USA. [Artinyan, Avo] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Artinyan, Avo] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Res Ctr Excellence, Houston, TX 77030 USA. [Artinyan, Avo] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv, Houston, TX 77030 USA. RP Kim, J (reprint author), City Hope Comprehens Canc Ctr, Dept Surg, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM jokim@coh.org RI Nelson, Rebecca/C-4438-2014 NR 32 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD JUN PY 2012 VL 27 IS 6 BP 737 EP 749 DI 10.1007/s00384-011-1378-2 PG 13 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 947VQ UT WOS:000304461400007 PM 22159751 ER PT J AU Mureithi, MW Poole, D Naranbhai, V Reddy, S Mkhwanazi, NP Sibeko, S Werner, L Karim, QA Karim, SA Ndung'u, T Altfeld, M AF Mureithi, Marianne W. Poole, Danielle Naranbhai, Vivek Reddy, Shabashini Mkhwanazi, Nompumelelo P. Sibeko, Sengeziwe Werner, Lise Karim, Quarraisha Abdool Karim, Salim Abdool Ndung'u, Thumbi Altfeld, Marcus CA CAPRISA 004 Trial Grp TI Preservation HIV-1-Specific IFN gamma+CD4+T-Cell Responses in Breakthrough Infections After Exposure to Tenofovir Gel in the CAPRISA 004 Microbicide Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; vaginal microbicide; tenofovir; HIV-1-specific CD4+T-cell help ID ACUTE HIV-1 INFECTION; T-CELL RESPONSES; DENDRITIC CELLS; CD4(+); VACCINE AB The Centre for the AIDS Program of Research in South Africa 004 trial demonstrated reduction of sexual HIV-1 acquisition in women using a vaginal microbicide containing tenofovir. A better understanding of the consequences of antiretroviral-containing microbicides for immune responses in individuals with intercurrent HIV-1 infection is needed for future trials combining the use of microbicides with HIV-1 vaccines. Investigation of immune responses in women who acquired HIV-1 although using tenofovir gel showed significantly higher (P = 0.01) Gag-specific IFN gamma+ CD4+ T-cell responses. The use of tenofovir-containing gel around the time of infection can modulate HIV-1 immunity, and these immunological changes need to be considered in future trials combining vaccines and microbicides. C1 [Altfeld, Marcus] Harvard Univ, Sch Med, Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Charlestown, MA 02129 USA. [Mureithi, Marianne W.; Poole, Danielle; Naranbhai, Vivek; Reddy, Shabashini; Mkhwanazi, Nompumelelo P.; Ndung'u, Thumbi; Altfeld, Marcus] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Program, Durban, South Africa. [Mureithi, Marianne W.; Poole, Danielle; Naranbhai, Vivek; Reddy, Shabashini; Mkhwanazi, Nompumelelo P.; Ndung'u, Thumbi; Altfeld, Marcus] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV KRITH, Durban, South Africa. [Naranbhai, Vivek; Sibeko, Sengeziwe; Werner, Lise; Karim, Quarraisha Abdool; Karim, Salim Abdool] Univ KwaZulu Natal, Ctr AIDS Program Res S Africa CAPRISA, Durban, South Africa. [Karim, Quarraisha Abdool; Karim, Salim Abdool] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Ragon Inst Massachusetts Gen Hosp MIT & Harvard, 149 13th St, Charlestown, MA 02129 USA. EM maltfeld@partners.org RI Abdool Karim, Salim Safurdeen/N-5947-2013 OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133 FU KwaZulu-Natal Research Institute for TB and HIV (K-RITH); Doris Duke Charitable Foundation; United States Agency for International Development (USAID); FHI360 [USAID] [GPO-A-00-05-00022-00, 132119]; Technology Innovation Agency (LIFElab) of the South African government's Department of Science Technology; CONRAD, Eastern Virginia Medical School [USAID] [GP00-08-00005-00, PPA-09-046]; National Institutes of Health Office of the Director, Fogarty International Center [R24 TW007988] FX Supported through the KwaZulu-Natal Research Institute for TB and HIV (K-RITH) and by a grant from the Doris Duke Charitable Foundation to MA. The parent trial (CAPRISA 004) was supported by the United States Agency for International Development (USAID), FHI360 [USAID co-operative agreement # GPO-A-00-05-00022-00, contract # 132119], and the Technology Innovation Agency (LIFElab) of the South African government's Department of Science & Technology. Tenofovir was provided by Gilead Sciences and the gel was manufactured and supplied for the CAPRISA 004 trial by CONRAD. The current studies are part of the CAPRISA TRAPS (Tenofovir gel Research for AIDS Prevention Science) Program, which is funded by CONRAD, Eastern Virginia Medical School [USAID co-operative grant # GP00-08-00005-00, subproject agreement # PPA-09-046]. The views expressed by the authors do not necessarily reflect the views of USAID, Gilead Sciences, Eastern Virginia Medical School or CONRAD.; The authors Q. A. K. and S. S. A. K. are coinventors with investigators from Gilead Sciences on two pending patents on tenofovir gel. The authors S. S. A. K. once received $2500 for serving on an Advisory Panel on PrEP for Merck. M. A. once received $1500 as a CME Honorarium from Gilead Science. M. W. M. was supported by the National Institutes of Health Office of the Director, Fogarty International Center, through the International Clinical Research Fellows Program at Vanderbilt (R24 TW007988). NR 22 TC 8 Z9 8 U1 0 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 2012 VL 60 IS 2 BP 124 EP 127 DI 10.1097/QAI.0b013e31824f53a9 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 947NL UT WOS:000304436600012 PM 22362152 ER PT J AU Mosam, A Shaik, F Uldrick, TS Esterhuizen, T Friedland, GH Scadden, DT Aboobaker, J Coovadia, HM AF Mosam, Anisa Shaik, Fahmida Uldrick, Thomas S. Esterhuizen, Tonya Friedland, Gerald H. Scadden, David T. Aboobaker, Jamila Coovadia, Hoosen M. TI A Randomized Controlled Trial of Highly Active Antiretroviral Therapy Versus Highly Active Antiretroviral Therapy and Chemotherapy in Therapy-Naive Patients With HIV-Associated Kaposi Sarcoma in South Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE Kaposi sarcoma; AIDS; HIV; highly active antiretroviral therapy; South Africa ID PEGYLATED-LIPOSOMAL DOXORUBICIN; QUALITY-OF-LIFE; MULTICENTRIC CASTLEMAN DISEASE; CLINICAL-TRIALS; IMMUNE RECONSTITUTION; INFLAMMATORY SYNDROME; AIDS; HERPESVIRUS; INDIVIDUALS; REPLICATION AB Background: The optimal approach to HIV-associated Kaposi sarcoma (HIV-KS) in sub-Saharan Africa is unknown. With large-scale rollout of highly active antiretroviral therapy (HAART) in South Africa, we hypothesized that survival in HIV-KS would improve and administration of chemotherapy in addition to HAART would be feasible and improve KS-specific outcomes. Methods: We conducted a randomized, controlled, open-label trial with intention-to-treat analysis. Treatment-naive patients from King Edward VIII Hospital, Durban, South Africa, a public-sector tertiary referral center, with HIV-KS, but no symptomatic visceral disease or fungating lesions requiring urgent chemotherapy, were randomized to HAART alone or HAART and chemotherapy (CXT). HAART arm received stavudine, lamivudine, and nevirapine (Triomune; CXT arm received Triomune plus bleomycin, doxorubicin, and vincristine every 3 weeks. When bleomycin, doxorubicin, and vincristine were not available, oral etoposide (50-100 mg for 1-21 days of a 28-day cycle) was substituted. Primary outcome was overall KS response using AIDS Clinical Trial Group criteria 12 months after HAART initiation. Secondary comparisons included time to response, progression-free survival, overall survival, adverse events, HIV control, CD4 reconstitution, adherence, and quality of life. Results: Fifty-nine subjects were randomized to HAART and 53 to CXT; 12-month overall KS response was 39% in the HAART arm and 66% in the CXT arm (difference, 27%; 95% confidence interval, 9%-43%; P = 0.005). At 12 months, 77% were alive (no survival difference between arms; P = 0.49), 82% had HIV viral load <50 copies per milliliter without difference between the arms (P = 0.47); CD4 counts and quality-of-life measures improved in all patients. Conclusions: HAART with chemotherapy produced higher overall KS response over 12 months, whereas HAART alone provided similar improvement in survival and select measures of morbidity. In Africa, with high prevalence of HIV and human herpes virus-8 and limited resources, HAART alone provides important benefit in patients with HIV-KS. C1 [Mosam, Anisa] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Dermatol, ZA-4013 Durban, South Africa. [Shaik, Fahmida; Uldrick, Thomas S.] Univ KwaZulu Natal, CAPRISA, ZA-4013 Durban, South Africa. [Uldrick, Thomas S.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Esterhuizen, Tonya] Univ KwaZulu Natal, Dept Bioeth, ZA-4013 Durban, South Africa. [Friedland, Gerald H.] Yale Univ, Dept Internal Med, Infect Dis Sect, Friedland AIDS Program, New Haven, CT USA. [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA USA. [Coovadia, Hoosen M.] Univ Witwatersrand, Johannesburg, South Africa. RP Mosam, A (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Dermatol, Rm 327 3rd Floor Med Sch,Private Bag X 7, ZA-4013 Durban, South Africa. EM mosama@ukzn.ac.za FU National Research Foundation [GUN 2054349]; National Cancer Institute AIDS Malignancy Consortium, an AIDS Community Research Initiative of America [14]; Fogarty International Center, National Institutes of Health [D43TW00231]; Irene Diamond Fund; Doris Duke Charitable Foundation FX Supported by the National Research Foundation Thuthuka Grant GUN 2054349, National Cancer Institute AIDS Malignancy Consortium Grant Supplement 14, an AIDS Community Research Initiative of America Grant, and a Training Supplement to the Columbia University-Southern African Fogarty AIDS International Training and Research Programme, Fogarty International Center, National Institutes of Health (grant # D43TW00231), and the Irene Diamond Fund and Doris Duke Charitable Foundation. Triomune donated by Cipla-Medpro. NR 35 TC 37 Z9 38 U1 0 U2 3 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 2012 VL 60 IS 2 BP 150 EP 157 DI 10.1097/QAI.0b013e318251aedd PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 947NL UT WOS:000304436600016 PM 22395672 ER PT J AU Vazquez, GH Tondo, L Mazzarini, L Gonda, X AF Vazquez, Gustavo H. Tondo, Leonardo Mazzarini, Lorenzo Gonda, Xenia TI Affective temperaments in general population: A review and combined analysis from national studies SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Affective temperament; Gender differences; General population; Nonclinical population; TEMPS-A ID A BUENOS-AIRES; TEMPS-A; PSYCHOMETRIC VALIDATION; INTERNAL CONSISTENCY; BEHAVIORAL-GENETICS; SAN-DIEGO; QUESTIONNAIRE; PERSONALITY; TRAITS; ENDOPHENOTYPE AB Background: The aim of this study was to investigate the characteristics of affective temperaments in general non-clinical population in different countries Method: We performed a detailed search of published studies (one unpublished) investigating affective temperaments in non-clinical populations by administering the Temperament Evaluation of Memphis, Paris and San Diego Auto-questionnaire (TEMPS-A) in its 110-items version. We have included a total of six studies published from different countries (Argentina, Germany, Hungary, Korea. Lebanon, and Portugal) and one unpublished with preliminary data from Spain. We analyzed the combined data from the collected studies. Results: We found significant gender differences, with men scoring higher in irritable and hyperthymic, and women in anxious, depressive and cyclothymic temperaments. Age had a significant effect in women with depressive temperament. Correlations among temperament scores have shown positive associations between depressive and anxious, and cyclothymic and irritable. Conclusions: There was a similarity in gender differences and the association between different affective temperaments. Our results indicate that affective temperaments show both universal and distinctive characteristics. Limitation: The sample populations in different countries were not homogeneous for age and socio-economic composition. In the Korean study of Kang et al. the version of the TEMPS was not validated. (C) 2011 Elsevier B.V. All rights reserved. C1 [Vazquez, Gustavo H.] Univ Palermo, Dept Neurosci, RA-1425 Buenos Aires, DF, Argentina. [Vazquez, Gustavo H.; Tondo, Leonardo] Harvard Univ, Sch Med, Dept Psychiat, Int Consortium Bipolar Disorders Res, Boston, MA 02115 USA. [Vazquez, Gustavo H.; Tondo, Leonardo] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Vazquez, Gustavo H.; Tondo, Leonardo] Massachusetts Gen Hosp, McLean Div, Belmont, MA USA. [Tondo, Leonardo] Lucio Bini Mood Disorder Ctr, Cagliari, Sardinia, Italy. [Mazzarini, Lorenzo] Univ Roma La Sapienza, Sch Med 2, St Andrea Hosp, Dept Neurosci,Unit Psychiat, Rome, Italy. [Mazzarini, Lorenzo] Suore Hosp Sacred Heart Jesus, Dept Neuropsychiat, Viterbo, Italy. [Gonda, Xenia] Semmelweis Univ, Dept Clin & Theoret Mental Hlth, Kutvolgyi Clin Ctr, Budapest, Hungary. [Gonda, Xenia] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Budapest, Hungary. RP Vazquez, GH (reprint author), Univ Palermo, Dept Neurosci, Mario Bravo 1259, RA-1425 Buenos Aires, DF, Argentina. EM gvazquez@palermo.edu NR 27 TC 23 Z9 23 U1 0 U2 4 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 2012 VL 139 IS 1 BP 18 EP 22 DI 10.1016/j.jad.2011.06.032 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 948GC UT WOS:000304490600003 PM 21774989 ER PT J AU Dip, PV Saw, WG Roessle, M Marshansky, V Gruber, G AF Dip, Phat Vinh Saw, Wuan Geok Roessle, Manfred Marshansky, Vladimir Grueber, Gerhard TI Solution structure of subunit a, a (104-363), of the Saccharomyces cerevisiae V-ATPase and the importance of its C-terminus in structure formation SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Vacuolar ATPase; V1VO ATPase; V-1 ATPase; Vph1p; Subunit a; Cytohesin-2; Small angle X-ray scattering ID ELECTRON-MICROSCOPY; VACUOLAR ATPASE; 3-DIMENSIONAL STRUCTURE; SOLUTION SCATTERING; EXCHANGE FACTOR; DOMAIN; ARNO; A2-SUBUNIT; PROTEINS AB The 95 kDa subunit a of eukaryotic V-ATPases consists of a C-terminal, ion-translocating part and an N-terminal cytosolic domain. The latter's N-terminal domain (similar to 40 kDa) is described to bind in an acidification-dependent manner with cytohesin-2 (ARNO), giving the V-ATPase the putative function as pH-sensing receptor. Recently, the solution structure of the very N-terminal segment of the cytosolic N-terminal domain has been solved. Here we produced the N-terminal truncated form SCa (104-363) of the N-terminal domain (SCa (1-363)) of the Saccharomyces cerevisiae V-ATPase and determined its low resolution solution structure, derived from SAXS data. SCa (104-363) shows an extended S-like conformation with a width of about 3.88 nm and a length of 11.4 nm. The structure has been superimposed into the 3D reconstruction of the related A(1)A(O) ATP synthase from Pyrococcus furiosus, revealing that the SCa (104-363) fits well into the density of the collar structure of the enzyme complex. To understand the importance of the C-terminus of the protein SCa (1-363), and to determine the localization of the N- and C-termini in SCa (104-363), the C-terminal truncated form SCa (106-324) was produced and analyzed by SAXS. Comparison of the SCa (104-363) and SCa (106-324) shapes showed that the additional loop region in SCa (104-363) consists of the C-terminal residues. Whereas SCa (104-363) is monomeric in solution, SCa (106-324) forms a dimer, indicating the importance of the very C-terminus in structure formation. Finally, the solution structure of SCa (104-363) and SCa (106-324) will be discussed in terms of the topological arrangement of subunit a and cytoheisn-2 in V-ATPases. C1 [Dip, Phat Vinh; Saw, Wuan Geok; Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Roessle, Manfred] DESY, EMBL, Hamburg Outstn, D-22603 Hamburg, Germany. [Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. RP Gruber, G (reprint author), Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore. EM ggrueber@ntu.edu.sg OI Dip, Phat Vinh/0000-0002-1535-9644 FU A*STAR BMRC [09/1/22/19/609] FX We thank Dr. S.M. Malathy Sony for her support in SAXS data analysis and art. Phat Vinh Dip is grateful to receive the Singapore International Graduate Award (SINGA). This research was supported by A*STAR BMRC (09/1/22/19/609). NR 29 TC 6 Z9 6 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD JUN PY 2012 VL 44 IS 3 BP 341 EP 350 DI 10.1007/s10863-012-9442-3 PG 10 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 949YG UT WOS:000304613700006 PM 22562380 ER PT J AU Mamon, HJ AF Mamon, Harvey J. TI Long-Term Follow-Up of a Paradigm-Changing Study: The Paradigm Still Holds SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RECTAL-CANCER; PREOPERATIVE RADIOTHERAPY; CHEMORADIATION THERAPY; NONOPERATIVE TREATMENT; PATHOLOGICAL RESPONSE; GASTRIC-CARCINOMA; PLUS RADIOTHERAPY; CHEMORADIOTHERAPY; TRIAL; SURVIVAL C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mamon, HJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2012 VL 30 IS 16 BP 1901 EP 1903 DI 10.1200/JCO.2012.41.8863 PG 3 WC Oncology SC Oncology GA 949SS UT WOS:000304596800005 PM 22529256 ER PT J AU Jakubowiak, AJ Benson, DM Bensinger, W Siegel, DSD Zimmerman, TM Mohrbacher, A Richardson, PG Afar, DEH Singhal, AK Anderson, KC AF Jakubowiak, Andrzej J. Benson, Don M. Bensinger, William Siegel, David S. D. Zimmerman, Todd M. Mohrbacher, Ann Richardson, Paul G. Afar, Daniel E. H. Singhal, Anil K. Anderson, Kenneth C. TI Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY AB Purpose To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM). Patients and Methods Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m(2) IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria. Results Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months. Conclusion The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM. C1 [Jakubowiak, Andrzej J.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Jakubowiak, Andrzej J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Jakubowiak, Andrzej J.; Benson, Don M.; Richardson, Paul G.; Anderson, Kenneth C.] Multiple Myeloma Res Consortium, Norwalk, CT USA. [Benson, Don M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Siegel, David S. D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Mohrbacher, Ann] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Afar, Daniel E. H.; Singhal, Anil K.] Abbott Biotherapeut, Redwood City, CA USA. [Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jakubowiak, AJ (reprint author), Univ Chicago, Med Ctr, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM ajakubowiak@medicine.bsd.uchicago.edu FU PDL BioPharma; Millennium Pharmaceuticals; Abbott Biotherapeutics FX William Bensinger, PDL BioPharma; David S. D. Siegel, Millennium Pharmaceuticals; Supported by Abbott Biotherapeutics. NR 16 TC 101 Z9 101 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 2012 VL 30 IS 16 BP 1960 EP 1965 DI 10.1200/JCO.2011.37.7069 PG 6 WC Oncology SC Oncology GA 949SS UT WOS:000304596800017 PM 22291084 ER PT J AU Fisch, MJ Lee, JW Weiss, M Wagner, LI Chang, VT Cella, D Manola, JB Minasian, LM McCaskill-Stevens, W Mendoza, TR Cleeland, CS AF Fisch, Michael J. Lee, Ju-Whei Weiss, Matthias Wagner, Lynne I. Chang, Victor T. Cella, David Manola, Judith B. Minasian, Lori M. McCaskill-Stevens, Worta Mendoza, Tito R. Cleeland, Charles S. TI Prospective, Observational Study of Pain and Analgesic Prescribing in Medical Oncology Outpatients With Breast, Colorectal, Lung, or Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RACIAL-DIFFERENCES; PREVALENCE; MANAGEMENT; CARE; COMMUNICATION; PERCEPTIONS; VALIDATION; PHYSICIANS; ATTITUDES; RELIEF AB Purpose Pain is prevalent among patients with cancer, yet pain management patterns in outpatient oncology are poorly understood. Patients and Methods A total of 3,123 ambulatory patients with invasive cancer of the breast, prostate, colon/rectum, or lung were enrolled onto this prospective study regardless of phase of care or stage of disease. At initial assessment and 4 to 5 weeks later, patients completed a 25-item measure of pain, functional interference, and other symptoms. Providers recorded analgesic prescribing. The pain management index was calculated to assess treatment adequacy. Results Of the 3,023 patients we identified to be at risk for pain, 2,026 (67%) reported having pain or requiring analgesics at initial assessment; of these 2,026 patients, 670 (33%) were receiving inadequate analgesic prescribing. We found no difference in treatment adequacy between the initial and follow-up visits. Multivariable analysis revealed that the odds of a non-Hispanic white patient having inadequate pain treatment were approximately half those of a minority patient after adjusting for other explanatory variables (odds ratio, 0.51; 95% CI, 0.37 to 0.70; P = .002). Other significant predictors of inadequate pain treatment were having a good performance status, being treated at a minority treatment site, and having nonadvanced disease without concurrent treatment. Conclusion Most outpatients with common solid tumors must confront issues related to pain and the use of analgesics. There is significant disparity in pain treatment adequacy, with the odds of undertreatment twice as high for minority patients. These findings persist over 1 month of follow-up, highlighting the complexity of these problems. C1 [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. [Lee, Ju-Whei; Manola, Judith B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Wagner, Lynne I.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Chang, Victor T.] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. [Chang, Victor T.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Minasian, Lori M.; McCaskill-Stevens, Worta] NCI, Bethesda, MD 20892 USA. RP Fisch, MJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Unit 410,1515 Holcombe Blvd, Houston, TX 77030 USA. EM mfisch@mdanderson.org FU Public Health Service [CA37604, CA23318, CA026582, CA17145]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX Supported in part by Public Health Service Grants No. CA37604, CA23318, CA026582, and CA17145 and grants from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 29 TC 89 Z9 91 U1 4 U2 17 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 2012 VL 30 IS 16 BP 1980 EP 1988 DI 10.1200/JCO.2011.39.2381 PG 9 WC Oncology SC Oncology GA 949SS UT WOS:000304596800020 PM 22508819 ER PT J AU Ignatiadis, M Singhal, SK Desmedt, C Haibe-Kains, B Criscitiello, C Andre, F Loi, S Piccart, M Michiels, S Sotiriou, C AF Ignatiadis, Michail Singhal, Sandeep K. Desmedt, Christine Haibe-Kains, Benjamin Criscitiello, Carmen Andre, Fabrice Loi, Sherene Piccart, Martine Michiels, Stefan Sotiriou, Christos TI Gene Modules and Response to Neoadjuvant Chemotherapy in Breast Cancer Subtypes: A Pooled Analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXPRESSION PROFILES; PREOPERATIVE CHEMOTHERAPY; MOLECULAR SUBTYPES; TARGETED THERAPIES; IMMUNE-RESPONSE; PHASE-3 TRIAL; MUTANT-CELLS; PROGNOSIS; SIGNATURE; SURVIVAL AB Purpose To investigate the association between chemotherapy response and gene expression modules describing important biologic processes and druggable oncogenic pathways in breast cancer (BC) subtypes. Patients and Methods We searched for publicly available gene expression studies evaluating anthracycline with or without taxane-based neoadjuvant chemotherapy and identified eight studies with 996 patients. We computed 17 gene modules and calculated odds ratios (ORs) for pathologic complete response (pCR) for one-unit increases in scaled modules with and without adjustment for clinicopathologic characteristics. Added predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and integrated discrimination index (IDI). We used the false discovery rate (FDR) to adjust for multiple testing. Results High immune module scores were associated with increased pCR probability in all BC subtypes. High module scores of chromosomal instability, phosphatase and tensin homolog (PTEN) loss, and E2F3 transcription factor were associated with increased pCR probability in estrogen receptor (ER) -negative/human epidermal growth factor receptor 2 (HER2) -negative and ER-positive/HER2-negative but not in HER2-positive tumors (interactions between HER2 and each of these modules for their association with pCR: P < .05; FDR, 0.17; trend for interaction between HER2 and PTEN). High values of insulin-like growth factor 1 activation module were associated with increased pCR probability only in ER-positive/HER2-negative tumors (interaction between insulin-like growth factor 1 and ER: P = .002; FDR, 0.03). When adding the immune module to clinicopathologic characteristics, we observed substantial increases in predictive accuracy for pCR in the HER2-positive subtype (IDI, 0.093; P = .004; increase in AUC from 0.760 to 0.836). Conclusion Different processes and pathways are associated with pCR in different BC subtypes. C1 [Ignatiadis, Michail] Univ Libre Brussels, Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Haibe-Kains, Benjamin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haibe-Kains, Benjamin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Andre, Fabrice] Univ Paris 11, Inst Gustave Roussy, Paris, France. RP Ignatiadis, M (reprint author), Univ Libre Brussels, Inst Jules Bordet, Dept Med Oncol, 121 Blvd Waterloo, B-1000 Brussels, Belgium. EM michail.ignatiadis@bordet.be RI Loi, Sherene/H-1979-2016; Haibe-Kains, Benjamin/D-3702-2011; Michiels, Stefan/L-1516-2013 OI Loi, Sherene/0000-0001-6137-9171; Desmedt, Christine/0000-0002-5223-5579; Haibe-Kains, Benjamin/0000-0002-7684-0079; Michiels, Stefan/0000-0002-6963-2968 FU Breast Cancer Research Foundation; Fonds de la Recherche Scientifique; MEDIC Foundation; la Fondation Luxembourgeoise contre le Cancer; Les Amis de l'Institut Bordet; Greek Ministry of Education, Lifelong Learning & Religious Affairs [266] FX Supported in part by grants from the Breast Cancer Research Foundation, Fonds de la Recherche Scientifique, MEDIC Foundation, la Fondation Luxembourgeoise contre le Cancer and "Les Amis de l'Institut Bordet" (M. I., C. S.) and by the Greek Operational Program "Education & Lifelong Learning" ESPA-THALIS #266 of the Greek Ministry of Education, Lifelong Learning & Religious Affairs (M.I.). NR 58 TC 113 Z9 116 U1 0 U2 6 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 2012 VL 30 IS 16 BP 1996 EP 2004 DI 10.1200/JCO.2011.39.5624 PG 9 WC Oncology SC Oncology GA 949SS UT WOS:000304596800022 PM 22508827 ER PT J AU Anesi, GL Levine, D Attar, EC Fathi, AT AF Anesi, George L. Levine, Danielle Attar, Eyal C. Fathi, Amir T. TI Bilateral Ear Swelling and Erythema After Chemotherapy: A Case of Ara-C Ears SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LEUKEMIA; THERAPY C1 [Anesi, George L.; Levine, Danielle; Attar, Eyal C.; Fathi, Amir T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Anesi, GL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2012 VL 30 IS 16 BP E146 EP E146 DI 10.1200/JCO.2011.39.5970 PG 1 WC Oncology SC Oncology GA 949SS UT WOS:000304596800001 PM 22508815 ER PT J AU Fiore, C Bailey, D Conlon, N Wu, XQ Martin, N Fiorentino, M Finn, S Fall, K Andersson, SO Andren, O Loda, M Flavin, R AF Fiore, Christopher Bailey, Dyane Conlon, Niamh Wu, Xiaoqiu Martin, Neil Fiorentino, Michelangelo Finn, Stephen Fall, Katja Andersson, Swen-Olof Andren, Ove Loda, Massimo Flavin, Richard TI Utility of multispectral imaging in automated quantitative scoring of immunohistochemistry SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID PTEN TUMOR-SUPPRESSOR; PROSTATE-CANCER; ALPHA-CATENIN; INTEROBSERVER REPRODUCIBILITY; RECEPTOR EXPRESSION; TISSUE MICROARRAY; BREAST-CARCINOMA; GROWTH; CELLS; OVEREXPRESSION AB Background Automated scanning devices and image analysis software provide a means to overcome the limitations of manual semiquantitative scoring of immunohistochemistry. Common drawbacks to automated imaging systems include an inability to classify tissue type and an inability to segregate cytoplasmic and nuclear staining. Methods Immunohistochemistry for the membranous marker a-catenin, the cytoplasmic marker stathmin and the nuclear marker Ki-67 was performed on tissue microarrays (TMA) of archival formalin-fixed paraffin-embedded tissue comprising 471 (alpha-catenin and stathmin) and 511 (Ki-67) cases of prostate adenocarcinoma. These TMA were quantitatively analysed using two commercially available automated image analysers, the Ariol SL-50 system and the Nuance system from CRi. Both systems use brightfield microscopy for automated, unbiased and standardised quantification of immunohistochemistry, while the Nuance system has spectral deconvolution capabilities. Results Overall concordance between scores from both systems was excellent (r=0.90; 0.83-0.95). The software associated with the multispectral imager allowed accurate automated classification of tissue type into epithelial glandular structures and stroma, and a single-step segmentation of staining into cytoplasmic or nuclear compartments allowing independent evaluation of these areas. The Nuance system, however, was not able to distinguish reliably between tumour and non-tumour tissue. In addition, variance in the labour and time required for analysis between the two systems was also noted. Conclusion Despite limitations, this study suggests some beneficial role for the use of a multispectral imaging system in automated analysis of immunohistochemistry. C1 [Conlon, Niamh; Finn, Stephen; Flavin, Richard] St James Hosp, Dept Pathol, Trinity Coll, Dublin 8, Ireland. [Fiore, Christopher; Bailey, Dyane; Wu, Xiaoqiu; Fiorentino, Michelangelo; Finn, Stephen; Loda, Massimo; Flavin, Richard] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Fiore, Christopher; Bailey, Dyane; Wu, Xiaoqiu; Fiorentino, Michelangelo; Finn, Stephen; Loda, Massimo; Flavin, Richard] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Martin, Neil] Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Pathol Unit, Addarii Inst, Bologna, Italy. [Fall, Katja] Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden. [Fall, Katja; Andersson, Swen-Olof; Andren, Ove] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Flavin, R (reprint author), St James Hosp, Dept Pathol, Trinity Coll, Jamess St, Dublin 8, Ireland. EM flavinrichard@gmail.com RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Finn, Stephen/0000-0002-8628-5814; Fall, Katja/0000-0002-3649-2639 FU Prostate Cancer Foundation; National Cancer Institute [RO1CA131945, PO1CA89021, P50 CA90381]; Linda and Arthur Gelb Center for Translational Research; Dana Farber Cancer Institute-Novartis FX ML is supported by the Prostate Cancer Foundation, the National Cancer Institute (RO1CA131945, PO1CA89021 and P50 CA90381), the Linda and Arthur Gelb Center for Translational Research and a gift from Nuclea Biomarkers to the Jimmy Fund and the Loda laboratory. ML is also the recipient of a grant from the Dana Farber Cancer Institute-Novartis Drug Development Program. NR 30 TC 20 Z9 21 U1 0 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD JUN PY 2012 VL 65 IS 6 BP 496 EP 502 DI 10.1136/jclinpath-2012-200734 PG 7 WC Pathology SC Pathology GA 949XE UT WOS:000304609900003 PM 22447914 ER PT J AU So, C Kirby, KA Mehta, K Hoffman, RM Powell, AA Freedland, SJ Sirovich, B Yano, EM Walter, LC AF So, Cynthia Kirby, Katharine A. Mehta, Kala Hoffman, Richard M. Powell, Adam A. Freedland, Stephen J. Sirovich, Brenda Yano, Elizabeth M. Walter, Louise C. TI Medical Center Characteristics Associated with PSA Screening in Elderly Veterans with Limited Life Expectancy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE PSA screening; regional variation; elderly; life expectancy ID PRIMARY-CARE PHYSICIANS; ANTIGEN TEST USE; PROSTATE-CANCER; COLORECTAL-CANCER; UNITED-STATES; DECISION-MAKING; MEN; OLDER; DETERMINANTS; COMORBIDITY AB Although guidelines recommend against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, screening is common. We sought to identify medical center characteristics associated with screening in this population. We conducted a prospective study of 622,262 screen-eligible men aged 70+ seen at 104 VA medical centers in 2003. Primary outcome was the percentage of men at each center who received PSA screening in 2003, based on VA data and Medicare claims. Men were stratified into life expectancy groups ranging from favorable (age 70-79 with Charlson score = 0) to limited (age 85+ with Charlson score a parts per thousand yen1 or age 70+ with Charlson score a parts per thousand yen4). Medical center characteristics were obtained from the 1999-2000 VA Survey of Primary Care Practices and publicly available VA data sources. Among 123,223 (20%) men with limited life expectancy, 45% received PSA screening in 2003. Across 104 VAs, the PSA screening rate among men with limited life expectancy ranged from 25-79% (median 43%). Higher screening was associated with the following center characteristics: no academic affiliation (50% vs. 43%, adjusted RR = 1.14, 95% CI 1.04-1.25), a ratio of midlevel providers to physicians a parts per thousand yen3:4 (55% vs. 45%, adjusted RR = 1.20, 95% CI 1.09-1.32) and location in the South (49% vs. 39% in the West, adjusted RR = 1.25, 95% CI 1.12-1.40). Use of incentives and high scores on performance measures were not independently associated with screening. Within centers, the percentages of men screened with limited and favorable life expectancies were highly correlated (r = 0.90). Substantial practice variation exists for PSA screening in older men with limited life expectancy across VAs. The high center-specific correlation of screening among men with limited and favorable life expectancies indicates that PSA screening is poorly targeted according to life expectancy. C1 [So, Cynthia] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Kirby, Katharine A.; Mehta, Kala; Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Hoffman, Richard M.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [Hoffman, Richard M.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Powell, Adam A.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Powell, Adam A.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Freedland, Stephen J.] Duke Univ, Durham VA Med Ctr, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Duke Prostate Ctr, Durham, NC USA. [Sirovich, Brenda] White River Junct VA, Windsor, VT USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, VA Greater Los Angeles Hlth Syst, VA HSR&D Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Yano, Elizabeth M.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Walter, LC (reprint author), VA Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA. EM Louise.Walter@ucsf.edu FU National Cancer Institute at the National Institutes of Health [R01 CA134425]; American Federation for Aging Research; National Institute on Aging [K-01AG025444]; New Mexico VA Health Care System; White River Junction VA; VA HSRD [05-195] FX This work was supported by the National Cancer Institute at the National Institutes of Health (grant number R01 CA134425) to [LW, RH, AP, and SF]; the Medical Student Training in Aging Research Program at the American Federation for Aging Research to [CS]; the National Institute on Aging (grant number K-01AG025444) to [KM]; the New Mexico VA Health Care System to [RH]; the White River Junction VA to [BS]; and the VA HSR&D Research Career Development Award (Project #05-195) to [EY]. NR 46 TC 8 Z9 8 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 2012 VL 27 IS 6 BP 653 EP 660 DI 10.1007/s11606-011-1945-9 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900009 PM 22180196 ER PT J AU Pandhi, N DeVoe, JE Schumacher, JR Bartels, C Thorpe, CT Thorpe, JM Smith, MA AF Pandhi, Nancy DeVoe, Jennifer E. Schumacher, Jessica R. Bartels, Christie Thorpe, Carolyn T. Thorpe, Joshua M. Smith, Maureen A. TI Number of First-Contact Access Components Required to Improve Preventive Service Receipt in Primary Care Homes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; preventive medicine; access to care; continuity of care; primary care; health care utilization; aging ID INFLUENZA VACCINATION; SCREENING MAMMOGRAPHY; METAANALYSIS; MORTALITY; ADULTS; CONTINUITY; COMMUNITY; DEATHS; US AB A fundamental aim of primary care redesign and the patient-centered medical home is improving access to care. Patients who report having a usual site of care and usual provider are more likely to receive preventive services, but less is known about the influence of specific components of first-contact access (e.g., availability of appointments, advice by telephone) on preventive services receipt. To examine the relationship between number of first-contact access components and receipt of recommended preventive services. Secondary survey data analysis. Five thousand five hundred and seven insured adults who had continuity with a usual primary care physician and participated in the 2003-2006 round of the Wisconsin Longitudinal Survey. Using multivariable logistic regression, we calculated adjusted risk ratios, adjusted predicted probabilities and 95% confidence intervals for each preventive service. Experiencing more first-contact access components was significantly associated with a higher rate of receiving cholesterol tests, flu shots and prostate exams but not mammography. There was variation in the number of components needed (between two and seven) to achieve a significant difference. Having an increasing number of first-access components in a primary care office may improve preventive services receipt, and more components may be required for those services requiring greater provider contact (e.g., prostate exam) versus those that require less (e.g., mammography). In primary care redesign, the largest gains in preventive services receipt likely will come with redesign of multiple components simultaneously. While our study is a necessary step towards broadly understanding the relationship between first-contact access and preventive service receipt, other important questions remain. Certain components may drive greater improvements in the receipt of different services, and the effect of some of these components may depend on individual patient characteristics. Further research is critical for understanding redesign strategies that may optimize preventive service delivery. C1 [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin Madison, Dept Family Med, Madison, WI USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin Madison, Dept Populat Hlth Sci, Madison, WI USA. [DeVoe, Jennifer E.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Schumacher, Jessica R.] Univ Florida Gainesville, Dept Hlth Serv Res Management & Policy, Gainesville, FL USA. [Bartels, Christie] Univ Wisconsin, Dept Med, Rheumatol Sect, Sch Med & Publ Hlth, Madison, WI USA. [Thorpe, Carolyn T.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.; Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Pandhi, Nancy; Schumacher, Jessica R.; Bartels, Christie; Thorpe, Carolyn T.; Thorpe, Joshua M.; Smith, Maureen A.] Univ Wisconsin, Hlth Innovat Program, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth Madison, Madison, WI 53706 USA. RP Pandhi, N (reprint author), 800 Univ Bay Dr,Box 9445, Madison, WI 53705 USA. EM nancy.pandhi@fammed.wisc.edu RI Thorpe, Joshua/C-1188-2013 FU University of Wisconsin Institute for Clinical and Translational Research (UW ICTR); NIH [1 UL1 RR025011]; National Institute on Aging [l K08 AG029527, R01 AG09775, R01 AG033285]; Agency for Healthcare Research and Quality (AHRQ) [K08 HS16181]; University of Wisconsin Carbone Cancer Center (UWCCC) from the National Cancer Institute [P30 CA014520]; Vilas Estate Trust; National Science Foundation; Spencer Foundation; Graduate School of the University of Wisconsin-Madison; UW School of Medicine and Public Health FX This project was supported by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) funded through an NIH Clinical and Translational Science Award (CTSA), grant number 1 UL1 RR025011. In addition, Nancy Pandhi is supported by a National Institute on Aging Mentored Clinical Scientist Research Career Development Award, grant number l K08 AG029527. Dr. DeVoe's time on this project was supported by grant number K08 HS16181 from the Agency for Healthcare Research and Quality (AHRQ). This project was also supported by the University of Wisconsin Carbone Cancer Center (UWCCC) Support Grant from the National Cancer Institute, grant number P30 CA014520. Additional support was provided by the UW School of Medicine and Public Health from the Wisconsin Partnership Program. This research uses data from the Wisconsin Longitudinal Study of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute on Aging (R01 AG09775, R01 AG033285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation, and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the Wisconsin Longitudinal Study is available from the Wisconsin Longitudinal Study, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, Wisconsin, 53706 and at http://www.ssc.wisc.edu/wlsresearch/data/. The view expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 37 TC 5 Z9 5 U1 1 U2 8 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 2012 VL 27 IS 6 BP 677 EP 684 DI 10.1007/s11606-011-1955-7 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900012 PM 22215269 ER PT J AU Chen, B Covinsky, KE Cenzer, IS Adler, N Williams, BA AF Chen, Bonnie Covinsky, Kenneth E. Cenzer, Irena Stijacic Adler, Nancy Williams, Brie A. TI Subjective Social Status and Functional Decline in Older Adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health disparities; functional decline; geriatrics; socioeconomic status; determinants of health ID SELF-RATED HEALTH; SOCIOECONOMIC-STATUS; UNITED-STATES; WHITEHALL-II; LIFE-COURSE; MORTALITY; INEQUALITIES; AMERICANS; POSITION; OUTCOMES AB It is unknown whether subjective assessment of social status predicts health outcomes in older adults. To describe the relationship between subjective social status and functional decline in older adults. Longitudinal cohort study. The Health and Retirement Study, a nationally representative survey of community-dwelling older adults (2004-2008). Two thousand five hundred and twenty-three community-dwelling older adults. Self-report of social status (SSS), categorized into three groups, reported by participants who marked a 10-rung ladder to represent where they stand in society. Four-year functional decline (new difficulty in any of five activities of daily living, mobility decline and/or death) Mean age was 64; 46% were male, 85% were white. At baseline, lower SSS was associated with being younger, unmarried, of nonwhite race/ethnicity, higher rates of chronic medical conditions and ADL impairment (P < 0.01). Over 4 years, 50% in the lowest SSS group declined in function, compared to the middle and highest groups (28% and 26%), P-trend < 0.001. Those in the lowest rungs of SSS were at increased risk of 4-year functional decline (unadjusted RR = 1.91, CI 1.-9-2.46). The relationship between a subjective belief that one is worse off than others and functional decline persisted after serial adjustment for demographics, objective SES measures, and baseline health and functional status (RR 1.36, CI 1.08-1.73). In older adults, the belief that one is in the lowest rungs of social status is a measure of socioeconomic distress and of significant risk for functional decline. These findings suggest that self-report of low subjective social status may give clinicians additional information about which older adults are at high risk for future functional decline. C1 [Covinsky, Kenneth E.; Cenzer, Irena Stijacic; Williams, Brie A.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.; Williams, Brie A.] Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco VA Med Ctr, San Francisco, CA USA. [Adler, Nancy] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Adler, Nancy] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Adler, Nancy] Univ Calif San Francisco, Ctr Hlth & Commun, San Francisco, CA 94143 USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. EM brie.williams@ucsf.edu FU Brookdale Leadership in Aging Fellowship; National Institute on Aging [K23AG033102, R01 AG028481, K24 AG029812]; UCSF Hartford Foundation Center of Excellence; Program for the Aging Century; MacArthur Foundation Research Network on Socioeconomic Status and Health; Veterans Affairs Medical Center, San Francisco, California FX Dr. Williams was funded by the Brookdale Leadership in Aging Fellowship, the National Institute on Aging (K23AG033102), the UCSF Hartford Foundation Center of Excellence Physician-Scholar Award and the Program for the Aging Century. Dr. Covinsky was supported by the National Institute on Aging (R01 AG028481and K24 AG029812). The R01 was administered by the Northern California Institute for Research and Education, and with resources of the San Francisco Veterans Affairs Medical Center. Dr. Adler received support from the MacArthur Foundation Research Network on Socioeconomic Status and Health. These funding sources 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. This work was supported with resources of the Veterans Affairs Medical Center, San Francisco, California. Drs. Williams and Covinsky are employees of the Department of Veterans Affairs. The opinions expressed in this manuscript may not represent those of the VA. NR 40 TC 17 Z9 17 U1 1 U2 12 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 2012 VL 27 IS 6 BP 693 EP 699 DI 10.1007/s11606-011-1963-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900014 PM 22215272 ER PT J AU Dinh, TA Alperin, P Walter, LC Smith, R AF Dinh, Tuan A. Alperin, Peter Walter, Louise C. Smith, Robert TI Impact of Comorbidity on Colorectal Cancer Screening Cost-Effectiveness Study in Diabetic Populations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE colorectal cancer screening; cost-effectiveness analysis; health care modeling; comorbidity; optimal screening cessation; individualized guidelines ID SERVICES TASK-FORCE; FECAL OCCULT BLOOD; ADJUSTED LIFE-YEAR; UNITED-STATES; PHYSICAL-ACTIVITY; AMERICAN-COLLEGE; WOMENS HEALTH; EQ-5D INDEX; RISK; COLONOSCOPY AB Although comorbidity has been shown to affect the benefits and risks of colorectal cancer (CRC) screening, it has not been accounted for in prior cost-effectiveness analyses of CRC screening. To evaluate the impact of diagnosis of diabetes mellitus, a highly prevalent comorbidity in U.S. adults aged 50 and older, on health and economic outcomes of CRC screening. Cost-effectiveness analysis using an integrated modeling framework. Derived from basic and epidemiologic studies, clinical trials, cancer registries, and a colonoscopy database. U.S. 50-year-old population. Lifetime. Costs are based on Medicare reimbursement rates. Colonoscopy screening at ten-year intervals, beginning at age 50, and discontinued after age 50, 60, 70, 80 or death. Health outcomes and cost effectiveness. Diabetes diagnosis significantly affects cost-effectiveness of CRC screening. For the same CRC screening strategy, a person without diabetes at age 50 gained on average 0.07-0.13 life years more than a person diagnosed with diabetes at age 50 or younger. For a population of 1,000 patients diagnosed with diabetes at baseline, increasing stop age from 70 years to 80 years increased quality-adjusted life years (QALYs) gained by 0.3, with an incremental cost-effectiveness ratio of $206,671/QALY. The corresponding figures for 1,000 patients without diabetes are 2.3 QALYs and $46,957/QALY. Cost-effectiveness results are sensitive to cost of colonoscopy and adherence to colonoscopy screening. Results depend on accuracy of model assumptions. Benefits of CRC screening differ substantially for patients with and without diabetes. Screening for CRC in patients diagnosed with diabetes at age 50 or younger is not cost-effective beyond age 70. Screening recommendations should be individualized based on the presence of comorbidities. C1 [Dinh, Tuan A.; Alperin, Peter] Archimedes Inc, San Francisco, CA 94105 USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Smith, Robert] Amer Canc Soc, Canc Control Dept, Atlanta, GA 30329 USA. RP Dinh, TA (reprint author), Archimedes Inc, 201 Mission St,29th Floor, San Francisco, CA 94105 USA. EM tuan.dinh@archimedesmodel.com FU National Cancer Institute [1R01CA134425] FX The authors declare no conflict of interest. This study was carried out by Archimedes in collaboration with Drs. Smith and Walter. Dr. Walter is supported by a grant 1R01CA134425 from the National Cancer Institute. NR 68 TC 5 Z9 5 U1 0 U2 4 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 2012 VL 27 IS 6 BP 730 EP 738 DI 10.1007/s11606-011-1972-6 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900018 PM 22237663 ER PT J AU Vick, A Kraemer, RR Morris, JL Willett, LL Centor, RM Estrada, CA Rodriguez, JM AF Vick, Amanda Kraemer, Ryan R. Morris, Jason L. Willett, Lisa L. Centor, Robert M. Estrada, Carlos A. Rodriguez, J. Martin TI A 60-Year-Old Woman with Chorea and Weight Loss SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE diagnostic reasoning; clinical problem solving; dual process theory; illness scripts; chorea; paraneoplastic syndrome ID STRATEGIES; MODEL C1 [Vick, Amanda; Kraemer, Ryan R.; Morris, Jason L.; Willett, Lisa L.; Centor, Robert M.; Estrada, Carlos A.; Rodriguez, J. Martin] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Kraemer, Ryan R.; Morris, Jason L.; Centor, Robert M.; Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. RP Rodriguez, JM (reprint author), Univ Alabama Birmingham, THT 229 1530 3rd Ave S, Birmingham, AL 35294 USA. EM mrodri2@uab.edu NR 11 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 2012 VL 27 IS 6 BP 747 EP 751 DI 10.1007/s11606-011-1928-x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 947BZ UT WOS:000304402900021 PM 22143453 ER PT J AU Baffy, G Brunt, EM Caldwell, SH AF Baffy, Gyoergy Brunt, Elizabeth M. Caldwell, Stephen H. TI Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace SO JOURNAL OF HEPATOLOGY LA English DT Review DE Non-alcoholic fatty liver disease; Hepatocellular carcinoma; Hepatocarcinogenesis; Cancer surveillance ID POPULATION-BASED COHORT; TNF-ALPHA PRODUCTION; TERM-FOLLOW-UP; INSULIN-RESISTANCE; HEPATITIS-C; DIABETIC-PATIENTS; RISK-FACTORS; CRYPTOGENIC CIRRHOSIS; METABOLIC SYNDROME; VIRAL-HEPATITIS AB Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Baffy, Gyoergy] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. [Baffy, Gyoergy] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02130 USA. [Brunt, Elizabeth M.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Caldwell, Stephen H.] Univ Virginia Hlth Syst, Digest Hlth Ctr Excellence, Div Gastroenterol & Hepatol, Charlottesville, VA USA. RP Baffy, G (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Gastroenterol Sect, 150 S Huntington Ave,Room 6A-46, Boston, MA 02130 USA. EM gbaffy@partners.org NR 115 TC 228 Z9 232 U1 5 U2 55 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2012 VL 56 IS 6 BP 1384 EP 1391 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 948OK UT WOS:000304512300026 PM 22326465 ER PT J AU Edlow, BL Takahashi, E Wu, ON Benner, T Dai, GP Bu, LH Grant, PE Greer, DM Greenberg, SM Kinney, HC Folkerth, RD AF Edlow, Brian L. Takahashi, Emi Wu, Ona Benner, Thomas Dai, Guangping Bu, Lihong Grant, Patricia Ellen Greer, David M. Greenberg, Steven M. Kinney, Hannah C. Folkerth, Rebecca D. TI Neuroanatomic Connectivity of the Human Ascending Arousal System Critical to Consciousness and Its Disorders SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Arousal; Ascending reticular activating system (ARAS); Brainstem; Consciousness; High angular resolution diffusion imaging (HARDI); Neuroanatomy; Tractography ID TRAUMATIC BRAIN-INJURY; STATE FREE PRECESSION; INTRALAMINAR THALAMIC NUCLEI; PERSISTENT VEGETATIVE STATE; DIFFUSION-TENSOR; WHITE-MATTER; RETICULAR-FORMATION; CEREBRAL-CORTEX; MRI DATA; TRACTOGRAPHY AB The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the human ARAS is poorly understood. We applied the advanced imaging technique of high angular resolution diffusion imaging (HARDI) to elucidate the structural connectivity of the ARAS in 3 adult human brains, 2 of which were imaged postmortem. High angular resolution diffusion imaging tractography identified the ARAS connectivity previously described in animals and also revealed novel human pathways connecting the brainstem to the thalamus, the hypothalamus, and the basal forebrain. Each pathway contained different distributions of fiber tracts from known neurotransmitter-specific ARAS nuclei in the brainstem. The histologically guided tractography findings reported here provide initial evidence for human-specific pathways of the ARAS. The unique composition of neurotransmitter-specific fiber tracts within each ARAS pathway suggests structural specializations that subserve the different functional characteristics of human arousal. This ARAS connectivity analysis provides proof of principle that HARDI tractography may affect the study of human consciousness and its disorders, including in neuropathologic studies of patients dying in coma and the persistent vegetative state. C1 [Edlow, Brian L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Folkerth, Rebecca D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Takahashi, Emi; Grant, Patricia Ellen] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Newborn Med, Boston, MA USA. [Takahashi, Emi; Grant, Patricia Ellen] Harvard Univ, Sch Med, Childrens Hosp Boston, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. [Bu, Lihong] Harvard Univ, Sch Med, Childrens Hosp Boston, FM Kirby Neurobiol Ctr, Boston, MA USA. [Grant, Patricia Ellen] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Boston, MA 02115 USA. [Kinney, Hannah C.; Folkerth, Rebecca D.] Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp Boston, Boston, MA 02115 USA. [Edlow, Brian L.; Greer, David M.; Greenberg, Steven M.] Harvard Univ, Sch Med, Dept Neurol, J Philip Kistler Stroke Res Ctr,Massachusetts Gen, Boston, MA 02115 USA. [Wu, Ona] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Edlow, Brian L.; Takahashi, Emi; Wu, Ona; Benner, Thomas; Dai, Guangping; Grant, Patricia Ellen] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, Yale New Haven Hosp, New Haven, CT 06510 USA. RP Edlow, BL (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM bedlow@partners.org FU National Institutes of Health [R25 NS065743, R01 HD20991, R21 HD069001, P41 RR14075]; Center for Integration of Medicine & Innovative Technology; Neuropathology Division, Department of Pathology, Brigham and Women's Hospital, Boston, MA; National Center for Research Resources [1S10RR016811-01] FX This work was supported by grants from the National Institutes of Health (R25 NS065743 [B. L. E.], R01 HD20991 [H. C. K.], R21 HD069001 [E. T.], and P41 RR14075 [Athinoula A. Martinos Center for Biomedical Imaging]) and by the Center for Integration of Medicine & Innovative Technology, and by the Neuropathology Division, Department of Pathology, Brigham and Women's Hospital, Boston, MA. This work also involved the use of instrumentation supported by the National Center for Research Resources (1S10RR016811-01). NR 80 TC 47 Z9 48 U1 3 U2 13 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 2012 VL 71 IS 6 BP 531 EP 546 DI 10.1097/NEN.0b013e3182588293 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600006 PM 22592840 ER PT J AU William, C Andermann, M Goldey, G Roumis, D Reid, RC Shatz, C Albers, M Frosch, M Hyman, B AF William, Christopher Andermann, Mark Goldey, Glenn Roumis, Demetris Reid, R. Clay Shatz, Carla Albers, Mark Frosch, Matthew Hyman, Bradley TI Early Visual System Synaptic Plasticity Defects in Alzheimer Disease Model Transgenic Mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [William, Christopher; Frosch, Matthew] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02114 USA. [Andermann, Mark; Goldey, Glenn; Roumis, Demetris; Reid, R. Clay] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Shatz, Carla] Stanford Univ, Stanford, CA 94305 USA. [Albers, Mark; Hyman, Bradley] MGH, MassGen Inst Neurodegenerat Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 14 BP 550 EP 551 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600021 ER PT J AU McGuone, D Stemmer-Rachamimov, A Stone, J Deshpande, V AF McGuone, Declan Stemmer-Rachamimov, Anat Stone, John Deshpande, Vikram TI Lymphoplasmacytic Hypophysitis: An IgG4-related Disease? SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [McGuone, Declan; Stemmer-Rachamimov, Anat; Stone, John; Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 37 BP 557 EP 557 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600044 ER PT J AU Auluck, P Lindquist, S AF Auluck, Pavan Lindquist, Susan TI Cytoprotective chemical screens in a yeast model for alpha-synucleinopathies SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [Auluck, Pavan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lindquist, Susan] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 70 BP 566 EP 566 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600077 ER PT J AU Auluck, P Lindquist, S AF Auluck, Pavan Lindquist, Susan TI Retrograde Trafficking Defects Enhance alpha-Synuclein Toxicity in a Yeast Model SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [Auluck, Pavan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lindquist, Susan] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 74 BP 567 EP 567 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600081 ER PT J AU Suva, M Rheinbay, E Chi, A Louis, D Bernstein, B AF Suva, Mario Rheinbay, Esther Chi, Andrew Louis, David Bernstein, Bradley TI Chromatin Landscape Analysis to Identify the Core Transcriptional Regulatory Network of Glioblastoma Cancer Stem Cells SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [Suva, Mario; Rheinbay, Esther; Louis, David; Bernstein, Bradley] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chi, Andrew] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 115 BP 578 EP 579 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600122 ER PT J AU Ciarlini, P Wood, B Klein, J Lyons, J Milner, D Philips, R Schutten, M Henrich, T Johnson, J Gabuzda, D De Girolami, U Folkerth, R AF Ciarlini, Pedro Wood, Brian Klein, Joshua Lyons, Jennifer Milner, Danny Philips, Richard Schutten, Martin Henrich, Timothy Johnson, Jennifer Gabuzda, Dana De Girolami, Umberto Folkerth, Rebecca TI Biopsy Pathology of HIV-2 Encephalitis: Case Report SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [Ciarlini, Pedro; Milner, Danny; De Girolami, Umberto; Folkerth, Rebecca] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wood, Brian; Henrich, Timothy; Johnson, Jennifer] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Klein, Joshua; Lyons, Jennifer; Philips, Richard] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Klein, Joshua] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Schutten, Martin] Erasmus MC, Dept Virol, Rotterdam, Netherlands. [Gabuzda, Dana] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 130 BP 583 EP 583 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600137 ER PT J AU McGuone, D Kimchi, E Neilan, A Robbins, G Frosch, M Hedley-Whyte, ET AF McGuone, Declan Kimchi, Eyal Neilan, Anne Robbins, Gregory Frosch, Matthew Hedley-Whyte, E. Tessa TI Rabies Encephalitis of Bat-strain Type in a 63 Year Old Man: Failure of the Milwaukee Protocol SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [McGuone, Declan; Kimchi, Eyal; Neilan, Anne; Robbins, Gregory; Frosch, Matthew; Hedley-Whyte, E. Tessa] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 135 BP 584 EP 584 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600142 ER PT J AU Ghetti, B Brashear, A Hagen, M Sweadner, K AF Ghetti, Bernardino Brashear, Allison Hagen, Matthew Sweadner, Kathleen TI Rapid Onset Dystonia-Parkinsonism Associated with the I758S ATP1A3 Mutation: A Neuropathologic Study of Two Affected Siblings SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 88th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 21-24, 2012 CL Chicago, IL SP Amer Assoc Neuropathol C1 [Ghetti, Bernardino] Indiana Univ, Bloomington, IN 47405 USA. [Brashear, Allison] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hagen, Matthew] Univ Cincinnati, Cincinnati, OH 45221 USA. [Sweadner, Kathleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Brashear, Allison/G-3853-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2012 VL 71 IS 6 MA 166 BP 592 EP 593 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 949QB UT WOS:000304589600173 ER PT J AU Hulten, EA Bittencourt, MS Ghoshhajra, B Blankstein, R AF Hulten, Edward A. Bittencourt, Marcio Sommer Ghoshhajra, Brian Blankstein, Ron TI Stress CT perfusion: Coupling coronary anatomy with physiology SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Computed tomography (CT); coronary artery disease; ischemia; myocardial; vasodilator stress ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; FRACTIONAL FLOW RESERVE; DUAL-SOURCE CT; MYOCARDIAL-PERFUSION; ARTERY-DISEASE; DIAGNOSTIC PERFORMANCE; PROGNOSTIC VALUE; MAGNETIC-RESONANCE; CARDIAC RISK; SPECT AB While multiple different imaging tests can be used to evaluate patients with known or suspected coronary artery disease (CAD), each of them is designed to evaluate either coronary anatomy or physiology. Recently, it has been recognized that cardiac CT can be used to evaluate stress and rest myocardial perfusion in addition to its capabilities to image the coronary arteries, thus allowing for the simultaneous evaluation of the anatomical burden and physiological significance of CAD in a single exam. In this review, the strengths and the limitations of imaging coronary anatomy and myocardial perfusion will be discussed. Next, key technical aspects of how to perform and interpret CT perfusion imaging will be summarized while providing an update of the most recent data in this emerging field. Finally, future directions and opportunities for further research will be discussed. C1 [Hulten, Edward A.; Bittencourt, Marcio Sommer; Blankstein, Ron] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. [Hulten, Edward A.; Bittencourt, Marcio Sommer; Blankstein, Ron] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Div Cardiovasc, Dept Radiol, Boston, MA 02115 USA. [Blankstein, Ron] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ghoshhajra, Brian] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Blankstein, R (reprint author), Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM rblankstein@partners.org RI Ghoshhajra, Brian/J-2114-2016; Bittencourt, Marcio/C-1444-2011; OI Ghoshhajra, Brian/0000-0002-3865-3432; Bittencourt, Marcio/0000-0002-3711-1754; Hulten, Edward/0000-0001-9281-0032 NR 57 TC 13 Z9 13 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUN PY 2012 VL 19 IS 3 BP 588 EP 600 DI 10.1007/s12350-012-9546-5 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 947BO UT WOS:000304401800023 PM 22456969 ER PT J AU Kwon, JY Campbell, JT Myerson, MS AF Kwon, John Y. Campbell, John T. Myerson, Mark S. TI Posterior Tibial Tendon Tear After 4-Cortex Syndesmotic Screw Fixation: A Case Report and Literature Review SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE posterior tibial tendon tear; four cortice syndesmotic screw fixation; syndesmotic screw fixation ID CLOSED ANKLE FRACTURE; RUPTURE; REMOVAL; DISLOCATION AB We describe a previously unreported problem of a patient who underwent errant 4-cortex syndesmotic screw fixation with resultant posterior tibial tendon tear necessitating removal of hardware and repair of a tendon tear. C1 [Kwon, John Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Campbell, John T.; Myerson, Mark S.] Inst Foot & Ankle Reconstruct Mercy, Baltimore, MD USA. RP Kwon, JY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM johnkwonmd@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 0 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 2012 VL 26 IS 6 BP E66 EP E69 DI 10.1097/BOT.0b013e31821e127f PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 947FO UT WOS:000304414300007 PM 21849910 ER PT J AU Makino, CL AF Makino, Clint L. TI Easy does it when bleaching isolated mouse rods SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material C1 [Makino, Clint L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Makino, Clint L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Makino, CL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cmakino@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 NR 4 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN PY 2012 VL 590 IS 11 BP 2551 EP 2552 DI 10.1113/jphysiol.2012.233643 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 950OZ UT WOS:000304659900006 PM 22787167 ER PT J AU Spina, JL McIntyre, CL Pulcini, JA AF Spina, Jennifer L. McIntyre, C. Lynne Pulcini, Joyce A. TI An Intervention to Increase High School Students' Compliance With Carrying Auto-Injectable Epinephrine: A MASNRN Study SO JOURNAL OF SCHOOL NURSING LA English DT Article DE allergies; adolescents; evidence-based practice; epinephrine ID ALLERGIC REACTIONS; FOOD ALLERGY; ANAPHYLACTIC REACTIONS; UNITED-STATES; CHILDREN AB Adolescents with life-threatening allergies are at a greater risk for a fatal anaphylactic event since only about half of them carry unexpired epinephrine available for emergency use. The aim of this study was to test the effectiveness of school nurse interventions that consisted of either routine or periodic checks during the school year for the availability of unexpired auto-injectable epinephrine. Seventy-seven students from 11 Massachusetts high schools participated in this study. Descriptive and chi-square (chi(2)) statistics as well as the Fisher's exact test were used to analyze data. Findings suggest that while periodic checks for the availability of epinephrine throughout the school year do not increase the likelihood that students will have epinephrine available, those students who do carry their epinephrine are more likely to have unexpired medication with periodic reminders during the school year. C1 [Spina, Jennifer L.] Massachusetts Gen Hosp Boys & Girls Clubs Boston, Lynn, MA 01904 USA. [McIntyre, C. Lynne] DotWell, Evaluat & Planning, Dorchester, MA USA. [Pulcini, Joyce A.] Boston Coll, Connell Sch Nursing, Boston, MA USA. RP Spina, JL (reprint author), Massachusetts Gen Hosp Boys & Girls Clubs Boston, 22 Maplewood Rd, Lynn, MA 01904 USA. EM jenniferspina@comcast.net FU NASN (National Association of School Nurses) FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The author(s) received a NASN (National Association of School Nurses) Research Award to conduct this research study. NR 27 TC 6 Z9 6 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1059-8405 J9 J SCH NURS JI J. Sch. Nurs. PD JUN PY 2012 VL 28 IS 3 BP 230 EP 237 DI 10.1177/1059840511431459 PG 8 WC Nursing SC Nursing GA 951DL UT WOS:000304700900010 PM 22217467 ER PT J AU Bober, S Falk, S Patendaude, A AF Bober, Sharon Falk, Sandy Patendaude, Andrea TI THE HIGH COST OF RISK REDUCTION: SEXUAL DYSFUNCTION IN YOUNG BRCA1/2 MUTATION CARRIERS AFTER PROPHYLACTIC OOPHORECTOMY AND NEXT STEPS FOR ADDRESSING INTERVENTION SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Bober, Sharon] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bober, Sharon; Falk, Sandy; Patendaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JUN PY 2012 VL 9 SU 3 SI SI BP 178 EP 178 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 950PH UT WOS:000304660700050 ER PT J AU Meissner, TB Li, A Kobayashi, KS AF Meissner, Torsten B. Li, Amy Kobayashi, Koichi S. TI NLRC5: a newly discovered MHC class I transactivator (CITA) SO MICROBES AND INFECTION LA English DT Review DE MHC class I; NLR proteins; CIITA ID COMPLEX CLASS-II; BARE LYMPHOCYTE SYNDROME; FAMILY-MEMBER NLRC5; GTP-BINDING DOMAIN; MICE LACKING; IFN-GAMMA; TRANSCRIPTIONAL REGULATION; ANTIGEN PRESENTATION; NATURAL-KILLER; PYRIN DOMAIN AB Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class 11 gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NI:.,R protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as "CITA" (MHC class I transactivator), a counterpart to CIITA. In addition to MHC class I genes, NLRC5 can induce the expression of beta 2M, TAP1 and LMP2, essential components of MHC class I antigen presentation. These findings indicate that NLRC5 and CIITA are transcriptional regulators that orchestrate the concerted expression of critical components in the MHC class I and MHC class 11 pathways, respectively. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02215 USA. [Meissner, Torsten B.; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. RP Kobayashi, KS (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Dana 1420A,450 Brookline Ave, Boston, MA 02215 USA. EM Koichi_Kobayashi@dfci.harvard.edu FU NIH; Crohn's and Colitis Foundation of America; Cancer Research Institute; Claudia Adams Barr Award; EMBO FX This work was supported by grants from the NIH and the Crohn's and Colitis Foundation of America (K.S.K.). K.S.K. is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award and T.B.M has been a recipient of the EMBO Long Term fellowship. The authors have no conflicting financial interests. NR 67 TC 20 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUN PY 2012 VL 14 IS 6 BP 477 EP 484 DI 10.1016/j.micinf.2011.12.007 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 948RI UT WOS:000304519900001 PM 22209772 ER PT J AU Zorick, T Lee, B Mandelkern, MA Fong, T Robertson, C Ghahremani, DG Brown, AK Sumerel, B London, ED AF Zorick, T. Lee, B. Mandelkern, M. A. Fong, T. Robertson, C. Ghahremani, D. G. Brown, A. K. Sumerel, B. London, E. D. TI Low striatal dopamine receptor availability linked to caloric intake during abstinence from chronic methamphetamine abuse SO MOLECULAR PSYCHIATRY LA English DT Letter ID FOOD C1 [Zorick, T.; Lee, B.; Fong, T.; Ghahremani, D. G.; Brown, A. K.; Sumerel, B.; London, E. D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Zorick, T.] Greater Los Angeles Vet Adm Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Mandelkern, M. A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Robertson, C.; London, E. D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [London, E. D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Zorick, T (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu FU NCRR NIH HHS [M01 RR000865, MO1 RR00865]; NIDA NIH HHS [R01 DA020726, P20 DA022539, R01 DA015179] NR 9 TC 4 Z9 4 U1 0 U2 0 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 2012 VL 17 IS 6 BP 569 EP 571 DI 10.1038/mp.2011.137 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 947TU UT WOS:000304454700002 PM 22024765 ER PT J AU Varma, D Chandrasekaran, S Sundin, LJR Reidy, KT Wan, XH Chasse, DAD Nevis, KR DeLuca, JG Salmon, ED Cook, JG AF Varma, Dileep Chandrasekaran, Srikripa Sundin, Lynsie J. R. Reidy, Karen T. Wan, Xiaohu Chasse, Dawn A. D. Nevis, Kathleen R. DeLuca, Jennifer G. Salmon, E. D. Cook, Jeanette Gowen TI Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore-microtubule attachment SO NATURE CELL BIOLOGY LA English DT Article ID DNA-REPLICATION; CHROMOSOME SEGREGATION; LIVING CELLS; MITOSIS; CHECKPOINT; INITIATION; GEMININ; COMPLEX; DYNEIN; ORC6 AB Cdt1, a protein critical for replication origin licensing in G1 phase, is degraded during S phase but re-accumulates in G2 phase. We now demonstrate that human Cdt1 has a separable essential mitotic function. Cdtl localizes to kinetochores during mitosis through interaction with the Hec1 component of the Ndc80 complex. G2-specific depletion of Cdtl arrests cells in late prometaphase owing to abnormally unstable kinetochore-microtubule (kMT) attachments and Mad1-dependent spindle-assembly-checkpoint activity. Cdtl binds a unique loop extending from the rod domain of Hec1 that we show is also required for kMT attachment. Mutation of the loop domain prevents Cdtl kinetochore localization and arrests cells in prometaphase. Super-resolution fluorescence microscopy indicates that Cdtl binding to the Hec1 loop domain promotes a microtubule-dependent conformational change in the Ndc80 complex in vivo. These results support the conclusion that Cdtl binding to Hec1 is essential for an extended Ndc80 configuration and stable kMT attachment. C1 [Varma, Dileep; Wan, Xiaohu; Salmon, E. D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Chandrasekaran, Srikripa; Cook, Jeanette Gowen] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Sundin, Lynsie J. R.; DeLuca, Jennifer G.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Reidy, Karen T.; Cook, Jeanette Gowen] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. [Chasse, Dawn A. D.] Duke Univ, Med Ctr, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA. [Nevis, Kathleen R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Salmon, ED (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA. EM tsalmon@email.unc.edu; jean_cook@med.unc.edu OI Cook, Jeanette/0000-0003-0849-7405 FU NIH [K01 CA094907, GM083024, GM24364, GM088371]; Pew Scholars Program in the Biomedical Sciences FX We thank A. Desai for providing Krill, Nsl1, Dsn1 and Spindly antibodies, A. Musacchio (Max Planck Institute of Molecular Physiology, Dortmund, Germany) for anti-Mad1, Zwint1 and ZW10 antibodies, B. Stillman (Cold Spring Harbor Laboratory, New York, USA) for anti-Orc6 antibody, S. Taylor (University of Manchester, UK) for anti-Bub1 and BubR1 antibodies, T. Stukenberg (University of Virginia at Charlottesville, Virginia, USA) for anti-Spc24 antibody, T. Yen (Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA) for anti-CENP-E antibody and I. Cheeseman (Whitehead Institute of Biomedical Research and MIT, Cambridge, Massachusetts, USA) for anti-Ska3 antibody. We are grateful to A. Desai (University of California San Diego, La Jolla, CA, USA), D. Cheerambathur, T. Stukenberg, K. Slep and T. Maresca for helpful discussions and to J. Mick for generating Hec1 constructs. We would also like to thank other members of the Salmon, Cook, A. Desai and J. Nevins laboratories for their support during this project. J.G.C. was supported by NIH K01 CA094907 and NIH GM083024, E.D.S. was supported by NIH GM24364 and J.G.D. was supported by NIH GM088371 and a grant from the Pew Scholars Program in the Biomedical Sciences. NR 43 TC 25 Z9 26 U1 0 U2 8 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 2012 VL 14 IS 6 BP 593 EP + DI 10.1038/ncb2489 PG 22 WC Cell Biology SC Cell Biology GA 949TW UT WOS:000304599900009 PM 22581055 ER PT J AU Kiezun, A Garimella, K Do, R Stitziel, NO Neale, BM McLaren, PJ Gupta, N Sklar, P Sullivan, PF Moran, JL Hultman, CM Lichtenstein, P Magnusson, P Lehner, T Shugart, YY Price, AL de Bakker, PIW Purcell, SM Sunyaev, SR AF Kiezun, Adam Garimella, Kiran Do, Ron Stitziel, Nathan O. Neale, Benjamin M. McLaren, Paul J. Gupta, Namrata Sklar, Pamela Sullivan, Patrick F. Moran, Jennifer L. Hultman, Christina M. Lichtenstein, Paul Magnusson, Patrik Lehner, Thomas Shugart, Yin Yao Price, Alkes L. de Bakker, Paul I. W. Purcell, Shaun M. Sunyaev, Shamil R. TI Exome sequencing and the genetic basis of complex traits SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; ALLELE FREQUENCY-SPECTRUM; RARE VARIANTS; POPULATION-STRUCTURE; PROTEIN FUNCTION; COMMON DISEASES; PLASMA-LEVELS; MUTATIONS; SELECTION C1 [Kiezun, Adam; McLaren, Paul J.; de Bakker, Paul I. W.; Sunyaev, Shamil R.] Harvard Univ, Sch Med, Dept Med, Div Genet,Brigham & Womens Hosp, Boston, MA 02114 USA. [Kiezun, Adam; Garimella, Kiran; Do, Ron; Stitziel, Nathan O.; Neale, Benjamin M.; McLaren, Paul J.; Gupta, Namrata; Moran, Jennifer L.; Price, Alkes L.; de Bakker, Paul I. W.; Sunyaev, Shamil R.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Do, Ron; Neale, Benjamin M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Stitziel, Nathan O.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Neale, Benjamin M.; Purcell, Shaun M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Friedman Brain Inst, New York, NY USA. [Sklar, Pamela] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, New York, NY USA. [Sullivan, Patrick F.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Hultman, Christina M.; Lichtenstein, Paul; Magnusson, Patrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Shugart, Yin Yao] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. RP Sunyaev, SR (reprint author), Harvard Univ, Sch Med, Dept Med, Div Genet,Brigham & Womens Hosp, Boston, MA 02114 USA. EM ssunyaev@rics.bwh.harvard.edu RI de Bakker, Paul/B-8730-2009; Magnusson, Patrik/C-4458-2017; OI de Bakker, Paul/0000-0001-7735-7858; lichtenstein, paul/0000-0003-3037-5287; Stitziel, Nathan/0000-0002-4963-8211; Moran, Jennifer/0000-0002-5664-4716 FU US National Institutes of Health (NIH) [5R01 MH084676]; Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation; NIH [AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556]; Herman Foundation; Stanley Medical Research Institute; National Institute of Mental Health (NIMH) [1R01MH089208-01]; Canadian Institutes of Health Research FX The authors are grateful to S. Pollack for assistance with EIGENSOFT. This work was made possible, in part, by the US National Institutes of Health (NIH; grant 5R01 MH084676) and, in part, by the International HIV Controllers Study, supported by the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation (to P.I.W.d.B.), and the AIDS Clinical Trials Group, supported by the NIH (grants AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853, AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634, AI069502, AI069419, AI068636, RR024975 and AI077505). Sequencing of the SCZ control individuals was funded by the NIH (grant RC2MH089905), the Herman Foundation and the Stanley Medical Research Institute. N.O.S. was supported, in part, by an NIH Training Grant (T32-HL07604-25; Division of Cardiovascular Medicine, Brigham and Women's Hospital). B.M.N. was supported by a National Institute of Mental Health (NIMH) grant (1R01MH089208-01). R. D. is supported by a Canadian Institutes of Health Research Banting Postdoctoral Fellowship. The views expressed in this paper do not necessarily represent the views of the NIMH, NIH, Department of Health and Human Services (HHS) or the US government. NR 97 TC 195 Z9 199 U1 1 U2 35 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 2012 VL 44 IS 6 BP 623 EP 630 DI 10.1038/ng.2303 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100006 PM 22641211 ER PT J AU Pasaniuc, B Rohland, N McLaren, PJ Garimella, K Zaitlen, N Li, H Gupta, N Neale, BM Daly, MJ Sklar, P Sullivan, PF Bergen, S Moran, JL Hultman, CM Lichtenstein, P Magnusson, P Purcell, SM Haas, DW Liang, LM Sunyaev, S Patterson, N de Bakker, PIW Reich, D Price, AL AF Pasaniuc, Bogdan Rohland, Nadin McLaren, Paul J. Garimella, Kiran Zaitlen, Noah Li, Heng Gupta, Namrata Neale, Benjamin M. Daly, Mark J. Sklar, Pamela Sullivan, Patrick F. Bergen, Sarah Moran, Jennifer L. Hultman, Christina M. Lichtenstein, Paul Magnusson, Patrik Purcell, Shaun M. Haas, David W. Liang, Liming Sunyaev, Shamil Patterson, Nick de Bakker, Paul I. W. Reich, David Price, Alkes L. TI Extremely low-coverage sequencing and imputation increases power for genome-wide association studies SO NATURE GENETICS LA English DT Article ID GENOTYPE; POPULATION; SCHIZOPHRENIA; FRAMEWORK; LINKAGE; MODELS AB Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5x) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24x average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power. C1 [Pasaniuc, Bogdan; Zaitlen, Noah; Liang, Liming; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pasaniuc, Bogdan; Zaitlen, Noah; Liang, Liming; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pasaniuc, Bogdan; Rohland, Nadin; McLaren, Paul J.; Garimella, Kiran; Zaitlen, Noah; Li, Heng; Gupta, Namrata; Neale, Benjamin M.; Daly, Mark J.; Bergen, Sarah; Moran, Jennifer L.; Purcell, Shaun M.; Liang, Liming; Sunyaev, Shamil; Patterson, Nick; de Bakker, Paul I. W.; Reich, David; Price, Alkes L.] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA. [Rohland, Nadin; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [McLaren, Paul J.; Sunyaev, Shamil; de Bakker, Paul I. W.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Neale, Benjamin M.; Daly, Mark J.; Purcell, Shaun M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Sklar, Pamela] Mt Sinai Sch Med, Friedman Brain Inst, Dept Psychiat, New York, NY USA. [Sklar, Pamela] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, New York, NY USA. [Sullivan, Patrick F.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Hultman, Christina M.; Lichtenstein, Paul; Magnusson, Patrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Haas, David W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. RP Pasaniuc, B (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM bpasaniu@hsph.harvard.edu; reich@genetics.med.harvard.edu; aprice@hsph.harvard.edu RI Pasaniuc, Bogdan/E-9310-2012; Bergen, Sarah/I-8313-2012; Li, Heng/D-9344-2011; de Bakker, Paul/B-8730-2009; Magnusson, Patrik/C-4458-2017 OI Bergen, Sarah/0000-0002-5888-0034; lichtenstein, paul/0000-0003-3037-5287; Moran, Jennifer/0000-0002-5664-4716; Li, Heng/0000-0003-4874-2874; de Bakker, Paul/0000-0001-7735-7858; FU US National Institutes of Health (NIH) [R01 HG006399, R01 MH084676]; NIH [P-30-AI060354, AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450]; NIMH [5RC2MH089905]; Sylvan Herman Foundation; Stanley Medical Research Institute FX We would like to acknowledge the ARRA Autism Sequencing Consortium (AASC) principal investigators for use of the autism data sets, including E. Boerwinkle, J.D. Buxbaum, E. H. Cook Jr., M.J. Daly (communicating principal investigator), B. Devlin, R. Gibbs, K. Roeder, A. Sabo, G. D. Schellenberg and J.S. Sutcliffe. We thank T. Lehner, A. Felsenfeld and P. Bender for their support and contribution to the AASC project and to the generation of AUT sequencing data. This research was supported by US National Institutes of Health (NIH) grants (R01 HG006399 to B. P., N.P., D. R. and A. L. P. and R01 MH084676 to S. S.). The IHCS acknowledges generous support from the Mark and Lisa Schwartz Foundation and the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation. The IHCS was also supported in part by NIH grants (P-30-AI060354 to the Harvard University Center for AIDS Research, AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853, AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634, AI069502, AI069419, AI068636 and RR024975 to the AIDS Clinical Trials Group and AI077505 to D. W. H.). Data generation for the NIMH controls was directly supported by NIH grants (R01MH089208, R01 MH089025, R01 MH089004 and R01 MH089482). SCZ data generation was supported by an NIMH grant (5RC2MH089905; P. S. and S. M. P.) and by the Sylvan Herman Foundation and the Stanley Medical Research Institute (a gift to the Stanley Center for Psychiatric Research). NR 29 TC 83 Z9 86 U1 1 U2 29 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 2012 VL 44 IS 6 BP 631 EP U41 DI 10.1038/ng.2283 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100007 PM 22610117 ER PT J AU Laurie, CC Laurie, CA Rice, K Doheny, KF Zelnick, LR McHugh, CP Ling, H Hetrick, KN Pugh, EW Amos, C Wei, QY Wang, LE Lee, JE Barnes, KC Hansel, NN Mathias, R Daley, D Beaty, TH Scott, AF Ruczinski, I Scharpf, RB Bierut, LJ Hartz, SM Landi, MT Freedman, ND Goldin, LR Ginsburg, D Li, J Desch, KC Strom, SS Blot, WJ Signorello, LB Ingles, SA Chanock, SJ Berndt, SI Le Marchand, L Henderson, BE Monroe, KR Heit, JA de Andrade, M Armasu, SM Regnier, C Lowe, WL Hayes, MG Marazita, ML Feingold, E Murray, JC Melbye, M Feenstra, B Kang, JH Wiggs, JL Jarvik, GP McDavid, AN Seshan, VE Mirel, DB Crenshaw, A Sharopova, N Wise, A Shen, J Crosslin, DR Levine, DM Zheng, XW Udren, JI Bennett, S Nelson, SC Gogarten, SM Conomos, MP Heagerty, P Manolio, T Pasquale, LR Haiman, CA Caporaso, N Weir, BS AF Laurie, Cathy C. Laurie, Cecelia A. Rice, Kenneth Doheny, Kimberly F. Zelnick, Leila R. McHugh, Caitlin P. Ling, Hua Hetrick, Kurt N. Pugh, Elizabeth W. Amos, Chris Wei, Qingyi Wang, Li-E Lee, Jeffrey E. Barnes, Kathleen C. Hansel, Nadia N. Mathias, Rasika Daley, Denise Beaty, Terri H. Scott, Alan F. Ruczinski, Ingo Scharpf, Rob B. Bierut, Laura J. Hartz, Sarah M. Landi, Maria Teresa Freedman, Neal D. Goldin, Lynn R. Ginsburg, David Li, Jun Desch, Karl C. Strom, Sara S. Blot, William J. Signorello, Lisa B. Ingles, Sue A. Chanock, Stephen J. Berndt, Sonja I. Le Marchand, Loic Henderson, Brian E. Monroe, Kristine R. Heit, John A. de Andrade, Mariza Armasu, Sebastian M. Regnier, Cynthia Lowe, William L. Hayes, M. Geoffrey Marazita, Mary L. Feingold, Eleanor Murray, Jeffrey C. Melbye, Mads Feenstra, Bjarke Kang, Jae H. Wiggs, Janey L. Jarvik, Gail P. McDavid, Andrew N. Seshan, Venkatraman E. Mirel, Daniel B. Crenshaw, Andrew Sharopova, Nataliya Wise, Anastasia Shen, Jess Crosslin, David R. Levine, David M. Zheng, Xiuwen Udren, Jenna I. Bennett, Siiri Nelson, Sarah C. Gogarten, Stephanie M. Conomos, Matthew P. Heagerty, Patrick Manolio, Teri Pasquale, Louis R. Haiman, Christopher A. Caporaso, Neil Weir, Bruce S. TI Detectable clonal mosaicism from birth to old age and its relationship to cancer SO NATURE GENETICS LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COPY-NUMBER VARIATION; POLYMORPHISM ARRAY ANALYSIS; B-CELL LYMPHOCYTOSIS; STEM-CELLS; GENOME; MALIGNANCIES; ASSOCIATION; GENE; POPULATIONS AB We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18). C1 [Laurie, Cathy C.; Laurie, Cecelia A.; Rice, Kenneth; Zelnick, Leila R.; McHugh, Caitlin P.; Shen, Jess; Crosslin, David R.; Levine, David M.; Zheng, Xiuwen; Udren, Jenna I.; Bennett, Siiri; Nelson, Sarah C.; Gogarten, Stephanie M.; Conomos, Matthew P.; Heagerty, Patrick; Weir, Bruce S.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Doheny, Kimberly F.; Ling, Hua; Hetrick, Kurt N.; Pugh, Elizabeth W.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. [Amos, Chris; Wei, Qingyi; Wang, Li-E] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Lee, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Div Surg, Houston, TX 77030 USA. [Barnes, Kathleen C.; Hansel, Nadia N.; Mathias, Rasika] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Daley, Denise] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Beaty, Terri H.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Scott, Alan F.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. [Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Scharpf, Rob B.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Bierut, Laura J.; Hartz, Sarah M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Landi, Maria Teresa; Freedman, Neal D.; Goldin, Lynn R.; Chanock, Stephen J.; Berndt, Sonja I.; Caporaso, Neil] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Ginsburg, David] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Ginsburg, David] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Li, Jun] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Desch, Karl C.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Blot, William J.; Signorello, Lisa B.] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Div Epidemiol, Nashville, TN USA. [Ingles, Sue A.; Henderson, Brian E.; Monroe, Kristine R.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Heit, John A.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [de Andrade, Mariza; Armasu, Sebastian M.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. [Regnier, Cynthia] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Regnier, Cynthia] Mayo Clin, Mayo Hyperoxaluria Ctr, Rochester, MN USA. [Lowe, William L.; Hayes, M. Geoffrey] Northwestern Univ, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. [Feingold, Eleanor] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Melbye, Mads; Feenstra, Bjarke] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Kang, Jae H.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wiggs, Janey L.; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jarvik, Gail P.] Univ Washington, Div Med Genet, Seattle, WA 98195 USA. [McDavid, Andrew N.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Seshan, Venkatraman E.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Mirel, Daniel B.; Crenshaw, Andrew] Broad Inst Harvard & MIT, Cambridge, MA USA. [Sharopova, Nataliya] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Wise, Anastasia; Manolio, Teri] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. RP Laurie, CC (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM cclaurie@u.washington.edu RI Weir, Bruce/A-2894-2013; Rice, Kenneth/A-4150-2013; Jarvik, Gail/N-6476-2014; Freedman, Neal/B-9741-2015; OI Rice, Kenneth/0000-0001-5779-4495; Jarvik, Gail/0000-0002-6710-8708; Freedman, Neal/0000-0003-0074-1098; Feenstra, Bjarke/0000-0003-1478-649X; Feingold, Eleanor/0000-0003-2898-6484; McDavid, Andrew/0000-0002-6581-1213; Zheng, Xiuwen/0000-0002-1390-0708; Gogarten, Stephanie/0000-0002-7231-9745; Hartz, Sarah/0000-0002-5429-3799 FU US National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI); NIH (NCI) [R29CA70334, R01CA100264, P50CA093459, U10AA008401, CA63464, CA54281, CA1326792, RC2 CA148085]; NIH [U01HG004738, HHSN268200782096C, U01HG004726, U01HG004735, U01HG004415, U01HG004423]; NIH (National Institute Dental and Craniofacial Research (NIDCR) [U01DE018993]; NIH, National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U01HG004422]; NIH, National Institute on Drug Abuse (NIDA) [P01CA089392, R01DA013423, R01DA019963]; NIH (NIDCR) [U01DE018903, R01DE014899]; NIH, NIH Center for Inherited Disease Research (CIDR) [HHSN268200-782096C]; NIH, National Eye Institute (NEI) [U01HG004728, R01EY015473, R01EY015872]; NIH, GENEVA Coordinating Center [U01 HG004446]; NIG, CIDR [HHSN268200782096C, U01HG004438]; NIH, Broad Center for Genotyping and Analysis [U01HG04424]; NIH, the National Library of Medicine; Division of Cancer Epidemiology and Genetics, NCI, NIH; Research to Prevent Blindness in NYC; Harvard Medical School; Harvard Glaucoma Center of Excellence; NCI [T32 CA09168] FX The GENEVA Consortium thanks the subjects and the staff of all GENEVA studies for their important contributions. We thank the following state cancer registries for their help: Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington and Wyoming. We thank C. Laird and G. Marti for helpful comments on the manuscript and B. Wakimoto and D. Gottschling for enlightening discussions. We also thank K. Jacobs for exchanging ideas and for working with us to estimate cross-method concordance of mosaic detection using the PLCO/GENEVA Lung Cancer study. Support for the GENEVA genome-wide association studies was provided through the US National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI). Some studies also received support from individual NIH Institutes. The grant numbers are: Melanoma (NCI R29CA70334, R01CA100264 and P50CA093459); Lung Health (U01HG004738); Cleft Lip/Palate (National Institute Dental and Craniofacial Research (NIDCR): U01DE018993 and NIH contract: HHSN268200782096C); Addiction (U01HG004422, National Institute on Alcohol Abuse and Alcoholism (NIAAA): U10AA008401, National Cancer Institute (NCI): P01CA089392, National Institute on Drug Abuse (NIDA): R01DA013423 and R01DA019963); Lung Cancer (Z01CP010200); Blood Clotting (R37 HL 039693); Prostate Cancer (U01HG004726, NCI: CA63464, CA54281, CA1326792 and RC2 CA148085); Venous Thromboembolism (U01HG004735); Birth Weight (U01HG004415); Dental Caries (NIDCR: U01DE018903 and R01DE014899, NIH Center for Inherited Disease Research (CIDR) contract: HHSN268200-782096C); Prematurity (U01HG004423); Glaucoma (U01HG004728, National Eye Institute (NEI): R01EY015473 and R01EY015872); GENEVA Coordinating Center (U01 HG004446); CIDR (U01HG004438 and HHSN268200782096C); Broad Center for Genotyping and Analysis (U01HG04424); the Intramural Research Program of the NIH, the National Library of Medicine; and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH. L. R. P. was also supported by a Physician Scientist award from Research to Prevent Blindness in NYC and an Ophthalmology Scholar Award from Harvard Medical School and from the Harvard Glaucoma Center of Excellence. L.R.Z. was supported by the NCI (T32 CA09168). NR 53 TC 161 Z9 161 U1 6 U2 36 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 2012 VL 44 IS 6 BP 642 EP U58 DI 10.1038/ng.2271 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100010 PM 22561516 ER PT J AU Jacobs, KB Yeager, M Zhou, WY Wacholder, S Wang, ZM Rodriguez-Santiago, B Hutchinson, A Deng, X Liu, CW Horner, MJ Cullen, M Epstein, CG Burdett, L Dean, MC Chatterjee, N Sampson, J Chung, CC Kovaks, J Gapstur, SM Stevens, VL Teras, LT Gaudet, MM Albanes, D Weinstein, SJ Virtamo, J Taylor, PR Freedman, ND Abnet, CC Goldstein, AM Hu, N Yu, K Yuan, JM Liao, LD Ding, T Qiao, YL Gao, YT Koh, WP Xiang, YB Tang, ZZ Fan, JH Aldrich, MC Amos, C Blot, WJ Bock, CH Gillanders, EM Harris, CC Haiman, CA Henderson, BE Kolonel, LN Le Marchand, L McNeill, LH Rybicki, BA Schwartz, AG Signorello, LB Spitz, MR Wiencke, JK Wrensch, M Wu, XF Zanetti, KA Ziegler, RG Figueroa, JD Garcia-Closas, M Malats, N Marenne, G Prokunina-Olsson, L Baris, D Schwenn, M Johnson, A Landi, MT Goldin, L Consonni, D Bertazzi, PA Rotunno, M Rajaraman, P Andersson, U Freeman, LEB Berg, CD Buring, JE Butler, MA Carreon, T Feychting, M Ahlbom, A Gaziano, JM Giles, GG Hallmans, G Hankinson, SE Hartge, P Henriksson, R Inskip, PD Johansen, C Landgren, A McKean-Cowdin, R Michaud, DS Melin, BS Peters, U Ruder, AM Sesso, HD Severi, G Shu, XO Visvanathan, K White, E Wolk, A Zeleniuch-Jacquotte, A Zheng, W Silverman, DT Kogevinas, M Gonzalez, JR Villa, O Li, DH Duell, EJ Risch, HA Olson, SH Kooperberg, C Wolpin, BM Jiao, L Hassan, M Wheeler, W Arslan, AA Bueno-de-Mesquita, HB Fuchs, CS Gallinger, S Gross, MD Holly, EA Klein, AP LaCroix, A Mandelson, MT Petersen, G Boutron-Ruault, MC Bracci, PM Canzian, F Chang, K Cotterchio, M Giovannucci, EL Goggins, M Bolton, JAH Jenab, M Khaw, KT Krogh, V Kurtz, RC McWilliams, RR Mendelsohn, JB Rabe, KG Riboli, E Tjonneland, A Tobias, GS Trichopoulos, D Elena, JW Yu, H Amundadottir, L Stolzenberg-Solomon, RZ Kraft, P Schumacher, F Stram, D Savage, SA Mirabello, L Andrulis, IL Wunder, JS Garcia, AP Sierrasesumaga, L Barkauskas, DA Gorlick, RG Purdue, M Chow, WH Moore, LE Schwartz, KL Davis, FG Hsing, AW Berndt, SI Black, A Wentzensen, N Brinton, LA Lissowska, J Peplonska, B McGlynn, KA Cook, MB Graubard, BI Kratz, CP Greene, MH Erickson, RL Hunter, DJ Thomas, G Hoover, RN Real, FX Fraumeni, JF Caporaso, NE Tucker, M Rothman, N Perez-Jurado, LA Chanock, SJ AF Jacobs, Kevin B. Yeager, Meredith Zhou, Weiyin Wacholder, Sholom Wang, Zhaoming Rodriguez-Santiago, Benjamin Hutchinson, Amy Deng, Xiang Liu, Chenwei Horner, Marie-Josephe Cullen, Michael Epstein, Caroline G. Burdett, Laurie Dean, Michael C. Chatterjee, Nilanjan Sampson, Joshua Chung, Charles C. Kovaks, Joseph Gapstur, Susan M. Stevens, Victoria L. Teras, Lauren T. Gaudet, Mia M. Albanes, Demetrius Weinstein, Stephanie J. Virtamo, Jarmo Taylor, Philip R. Freedman, Neal D. Abnet, Christian C. Goldstein, Alisa M. Hu, Nan Yu, Kai Yuan, Jian-Min Liao, Linda Ding, Ti Qiao, You-Lin Gao, Yu-Tang Koh, Woon-Puay Xiang, Yong-Bing Tang, Ze-Zhong Fan, Jin-Hu Aldrich, Melinda C. Amos, Christopher Blot, William J. Bock, Cathryn H. Gillanders, Elizabeth M. Harris, Curtis C. Haiman, Christopher A. Henderson, Brian E. Kolonel, Laurence N. Le Marchand, Loic McNeill, Lorna H. Rybicki, Benjamin A. Schwartz, Ann G. Signorello, Lisa B. Spitz, Margaret R. Wiencke, John K. Wrensch, Margaret Wu, Xifeng Zanetti, Krista A. Ziegler, Regina G. Figueroa, Jonine D. Garcia-Closas, Montserrat Malats, Nuria Marenne, Gaelle Prokunina-Olsson, Ludmila Baris, Dalsu Schwenn, Molly Johnson, Alison Landi, Maria Teresa Goldin, Lynn Consonni, Dario Bertazzi, Pier Alberto Rotunno, Melissa Rajaraman, Preetha Andersson, Ulrika Freeman, Laura E. Beane Berg, Christine D. Buring, Julie E. Butler, Mary A. Carreon, Tania Feychting, Maria Ahlbom, Anders Gaziano, J. Michael Giles, Graham G. Hallmans, Goran Hankinson, Susan E. Hartge, Patricia Henriksson, Roger Inskip, Peter D. Johansen, Christoffer Landgren, Annelie McKean-Cowdin, Roberta Michaud, Dominique S. Melin, Beatrice S. Peters, Ulrike Ruder, Avima M. Sesso, Howard D. Severi, Gianluca Shu, Xiao-Ou Visvanathan, Kala White, Emily Wolk, Alicja Zeleniuch-Jacquotte, Anne Zheng, Wei Silverman, Debra T. Kogevinas, Manolis Gonzalez, Juan R. Villa, Olaya Li, Donghui Duell, Eric J. Risch, Harvey A. Olson, Sara H. Kooperberg, Charles Wolpin, Brian M. Jiao, Li Hassan, Manal Wheeler, William Arslan, Alan A. Bueno-de-Mesquita, H. Bas Fuchs, Charles S. Gallinger, Steven Gross, Myron D. Holly, Elizabeth A. Klein, Alison P. LaCroix, Andrea Mandelson, Margaret T. Petersen, Gloria Boutron-Ruault, Marie-Christine Bracci, Paige M. Canzian, Federico Chang, Kenneth Cotterchio, Michelle Giovannucci, Edward L. Goggins, Michael Bolton, Judith A. Hoffman Jenab, Mazda Khaw, Kay-Tee Krogh, Vittorio Kurtz, Robert C. McWilliams, Robert R. Mendelsohn, Julie B. Rabe, Kari G. Riboli, Elio Tjonneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Elena, Joanne W. Yu, Herbert Amundadottir, Laufey Stolzenberg-Solomon, Rachael Z. Kraft, Peter Schumacher, Fredrick Stram, Daniel Savage, Sharon A. Mirabello, Lisa Andrulis, Irene L. Wunder, Jay S. Patino Garcia, Ana Sierrasesumaga, Luis Barkauskas, Donald A. Gorlick, Richard G. Purdue, Mark Chow, Wong-Ho Moore, Lee E. Schwartz, Kendra L. Davis, Faith G. Hsing, Ann W. Berndt, Sonja I. Black, Amanda Wentzensen, Nicolas Brinton, Louise A. Lissowska, Jolanta Peplonska, Beata McGlynn, Katherine A. Cook, Michael B. Graubard, Barry I. Kratz, Christian P. Greene, Mark H. Erickson, Ralph L. Hunter, David J. Thomas, Gilles Hoover, Robert N. Real, Francisco X. Fraumeni, Joseph F., Jr. Caporaso, Neil E. Tucker, Margaret Rothman, Nathaniel Perez-Jurado, Luis A. Chanock, Stephen J. TI Detectable clonal mosaicism and its relationship to aging and cancer SO NATURE GENETICS LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; GENOMIC IMBALANCES; MAFFUCCI SYNDROME; OLLIER DISEASE; MUTATIONS; SUSCEPTIBILITY; ASSOCIATION; ABERRATIONS; MECHANISMS; ANEUPLOIDY AB In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases. C1 [Jacobs, Kevin B.; Yeager, Meredith; Zhou, Weiyin; Wacholder, Sholom; Wang, Zhaoming; Hutchinson, Amy; Deng, Xiang; Liu, Chenwei; Horner, Marie-Josephe; Cullen, Michael; Epstein, Caroline G.; Burdett, Laurie; Chatterjee, Nilanjan; Sampson, Joshua; Chung, Charles C.; Kovaks, Joseph; Albanes, Demetrius; Weinstein, Stephanie J.; Taylor, Philip R.; Freedman, Neal D.; Abnet, Christian C.; Goldstein, Alisa M.; Hu, Nan; Yu, Kai; Liao, Linda; Ziegler, Regina G.; Figueroa, Jonine D.; Garcia-Closas, Montserrat; Prokunina-Olsson, Ludmila; Baris, Dalsu; Landi, Maria Teresa; Goldin, Lynn; Rotunno, Melissa; Rajaraman, Preetha; Freeman, Laura E. Beane; Hartge, Patricia; Inskip, Peter D.; Landgren, Annelie; Silverman, Debra T.; Mendelsohn, Julie B.; Tobias, Geoffrey S.; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael Z.; Savage, Sharon A.; Mirabello, Lisa; Purdue, Mark; Chow, Wong-Ho; Moore, Lee E.; Hsing, Ann W.; Berndt, Sonja I.; Black, Amanda; Wentzensen, Nicolas; Brinton, Louise A.; McGlynn, Katherine A.; Cook, Michael B.; Graubard, Barry I.; Kratz, Christian P.; Greene, Mark H.; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Caporaso, Neil E.; Tucker, Margaret; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Jacobs, Kevin B.; Yeager, Meredith; Zhou, Weiyin; Wang, Zhaoming; Hutchinson, Amy; Deng, Xiang; Liu, Chenwei; Cullen, Michael; Burdett, Laurie] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Rodriguez-Santiago, Benjamin; Villa, Olaya; Real, Francisco X.; Perez-Jurado, Luis A.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Rodriguez-Santiago, Benjamin; Villa, Olaya; Perez-Jurado, Luis A.] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain. [Rodriguez-Santiago, Benjamin; Villa, Olaya] qGenomics, Quantitat Genom Med Lab, Barcelona, Spain. [Dean, Michael C.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Gapstur, Susan M.; Stevens, Victoria L.; Teras, Lauren T.; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Yuan, Jian-Min] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN USA. [Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan, Peoples R China. [Qiao, You-Lin; Fan, Jin-Hu] Chinese Acad Med Sci, Dept Epidemiol, Canc Inst Hosp, Beijing 100730, Peoples R China. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China. [Koh, Woon-Puay] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37212 USA. [Aldrich, Melinda C.; Blot, William J.; Signorello, Lisa B.; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol,Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Amos, Christopher; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA. [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA. [Gillanders, Elizabeth M.; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Harris, Curtis C.; Zanetti, Krista A.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Haiman, Christopher A.; Henderson, Brian E.; McKean-Cowdin, Roberta; Schumacher, Fredrick; Stram, Daniel; Barkauskas, Donald A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Div Off Vice President Canc Prevent & Populat Sci, Houston, TX 77030 USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Ctr Community Engaged & Translat Res, Duncan Family Inst, Houston, TX 77030 USA. [Rybicki, Benjamin A.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA. [Signorello, Lisa B.; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Spitz, Margaret R.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Wiencke, John K.; Wrensch, Margaret] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Malats, Nuria; Marenne, Gaelle] CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Schwenn, Molly] Maine Canc Registry, Augusta, ME USA. [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA. [Consonni, Dario; Bertazzi, Pier Alberto] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy. [Consonni, Dario; Bertazzi, Pier Alberto] Osped Maggiore Policlin Mangiagalli & Regina Elen, Unit Epidemiol, Fdn Ist Ricevero & Cura Carattere Sci IRCCS, Milan, Italy. [Andersson, Ulrika; Henriksson, Roger; Melin, Beatrice S.] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Berg, Christine D.; Elena, Joanne W.] NCI, Clin & Translat Epidemiol Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA. [Butler, Mary A.; Carreon, Tania; Ruder, Avima M.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Feychting, Maria; Ahlbom, Anders] Karolinska Inst, Inst Environm Med, Div Epidemiol, S-10401 Stockholm, Sweden. [Gaziano, J. Michael] Harvard Univ, Sch Med, Div Aging, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hankinson, Susan E.; Wolpin, Brian M.; Fuchs, Charles S.; Giovannucci, Edward L.; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Henriksson, Roger] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Johansen, Christoffer; Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Michaud, Dominique S.; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Div Epidemiol & Biostat, London, England. [Michaud, Dominique S.] Brown Univ, Div Biol & Med, Dept Epidemiol, Providence, RI 02912 USA. [Peters, Ulrike; White, Emily; Kooperberg, Charles; LaCroix, Andrea; Mandelson, Margaret T.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Visvanathan, Kala; Bolton, Judith A. Hoffman] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. 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EM chanocks@mail.nih.gov RI Consonni, Dario/K-7943-2016; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; Beane Freeman, Laura/C-4468-2015; Kogevinas, Manolis/C-3918-2017; bertazzi, pietro alberto/D-5039-2017; Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; Garcia-Closas, Montserrat /F-3871-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; Malats, Nuria/H-7041-2015; Perez Jurado, Luis Alberto/M-7706-2015; Real Arribas, Francisco/H-5275-2015; Savage, Sharon/B-9747-2015; Krogh, Vittorio/K-2628-2016; Berg , Christine/K-1047-2014; Qiao, You-Lin/B-4139-2012; Dean, Michael/G-8172-2012; Ruder, Avima/I-4155-2012; Patino-Garcia, Ana/I-4299-2012; Peplonska, Beata/F-6004-2010; Aldrich, Melinda/C-7783-2013; Cook, Michael/A-5641-2009; Gallinger, Steven/E-4575-2013; Andrulis, Irene/E-7267-2013; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014 OI Lissowska, Jolanta/0000-0003-2695-5799; Yuan, Jian-Min/0000-0002-4620-3108; Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Consonni, Dario/0000-0002-8935-3843; Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Beane Freeman, Laura/0000-0003-1294-4124; bertazzi, pietro alberto/0000-0003-3475-2449; Duell, Eric J/0000-0001-5256-0163; Rodriguez-Santiago, Benjamin/0000-0003-1167-3852; Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Liao, Linda/0000-0002-1923-5294; Abnet, Christian/0000-0002-3008-7843; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098; Malats, Nuria/0000-0003-2538-3784; Real Arribas, Francisco/0000-0001-9501-498X; Savage, Sharon/0000-0001-6006-0740; Krogh, Vittorio/0000-0003-0122-8624; Qiao, You-Lin/0000-0001-6380-0871; Dean, Michael/0000-0003-2234-0631; Ruder, Avima/0000-0003-0419-6664; Cook, Michael/0000-0002-0533-7302; FU Intramural Research Program; US National Institutes of Health (NIH), NCI [HHSN261200800001E] FX This research was supported by the Intramural Research Program and by contract number HHSN261200800001E of the US National Institutes of Health (NIH), NCI. Support for each contributing study is listed in the Supplementary Note. We thank C. Laurie and B. Weir for constructive discussion and a comparison of methodology and results for the GENEVA study. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Cancer Institute, the National Institute for Occupational Safety and Health or the Maryland Cancer Registry. NR 43 TC 169 Z9 170 U1 2 U2 61 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 2012 VL 44 IS 6 BP 651 EP U68 DI 10.1038/ng.2270 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100011 PM 22561519 ER PT J AU Manning, AK Hivert, MF Scott, RA Grimsby, JL Bouatia-Naji, N Chen, H Rybin, D Liu, CT Bielak, LF Prokopenko, I Amin, N Barnes, D Cadby, G Hottenga, JJ Ingelsson, E Jackson, AU Johnson, T Kanoni, S Ladenvall, C Lagou, V Lahti, J Lecoeur, C Liu, YM Martinez-Larrad, MT Montasser, ME Navarro, P Perry, JRB Rasmussen-Torvik, LJ Salo, P Sattar, N Shungin, D Strawbridge, RJ Tanaka, T van Duijn, CM An, P de Andrade, M Andrews, JS Aspelund, T Atalay, M Aulchenko, Y Balkau, B Bandinelli, S Beckmann, JS Beilby, JP Bellis, C Bergman, RN Blangero, J Boban, M Boehnke, M Boerwinkle, E Bonnycastle, LL Boomsma, DI Borecki, IB Boettcher, Y Bouchard, C Brunner, E Budimir, D Campbell, H Carlson, O Chines, PS Clarke, R Collins, FS Corbaton-Anchuelo, A Couper, D de Faire, U Dedoussis, GV Deloukas, P Dimitriou, M Egan, JM Eiriksdottir, G Erdos, MR Eriksson, JG Eury, E Ferrucci, L Ford, I Forouhi, NG Fox, CS Franzosi, MG Franks, PW Frayling, TM Froguel, P Galan, P de Geus, E Gigante, B Glazer, NL Goel, A Groop, L Gudnason, V Hallmans, G Hamsten, A Hansson, O Harris, TB Hayward, C Heath, S Hercberg, S Hicks, AA Hingorani, A Hofman, A Hui, J Hung, J Jarvelin, MR Jhun, MA Johnson, PCD Jukema, JW Jula, A Kao, WH Kaprio, J Kardia, SLR Keinanen-Kiukaanniemi, S Kivimaki, M Kolcic, I Kovacs, P Kumari, M Kuusisto, J Kyvik, KO Laakso, M Lakka, T Lannfelt, L Lathrop, GM Launer, LJ Leander, K Li, G Lind, L Lindstrom, J Lobbens, S Loos, RJF Luan, JA Lyssenko, V Magi, R Magnusson, PKE Marmot, M Meneton, P Mohlke, KL Mooser, V Morken, MA Miljkovic, I Narisu, N O'Connell, J Ong, KK Oostra, BA Palmer, LJ Palotie, A Pankow, JS Peden, JF Pedersen, NL Pehlic, M Peltonen, L Penninx, B Pericic, M Perola, M Perusse, L Peyser, PA Polasek, O Pramstaller, PP Province, MA Raikkonen, K Rauramaa, R Rehnberg, E Rice, K Rotter, JI Rudan, I Ruokonen, A Saaristo, T Sabater-Lleal, M Salomaa, V Savage, DB Saxena, R Schwarz, P Seedorf, U Sennblad, B Serrano-Rios, M Shuldiner, AR Sijbrands, EJG Siscovick, DS Smit, JH Small, KS Smith, NL Smith, AV Stancakova, A Stirrups, K Stumvoll, M Sun, YV Swift, AJ Toenjes, A Tuomilehto, J Trompet, S Uitterlinden, AG Uusitupa, M Vikstrom, M Vitart, V Vohl, MC Voight, BF Vollenweider, P Waeber, G Waterworth, DM Watkins, H Wheeler, E Widen, E Wild, SH Willems, SM Willemsen, G Wilson, JF Witteman, JCM Wright, AF Yaghootkar, H Zelenika, D Zemunik, T Zgaga, L Wareham, NJ McCarthy, MI Barroso, I Watanabe, RM Florez, JC Dupuis, J Meigs, JB Langenberg, C AF Manning, Alisa K. Hivert, Marie-France Scott, Robert A. Grimsby, Jonna L. Bouatia-Naji, Nabila Chen, Han Rybin, Denis Liu, Ching-Ti Bielak, Lawrence F. Prokopenko, Inga Amin, Najaf Barnes, Daniel Cadby, Gemma Hottenga, Jouke-Jan Ingelsson, Erik Jackson, Anne U. Johnson, Toby Kanoni, Stavroula Ladenvall, Claes Lagou, Vasiliki Lahti, Jari Lecoeur, Cecile Liu, Yongmei Martinez-Larrad, Maria Teresa Montasser, May E. Navarro, Pau Perry, John R. B. Rasmussen-Torvik, Laura J. Salo, Perttu Sattar, Naveed Shungin, Dmitry Strawbridge, Rona J. Tanaka, Toshiko van Duijn, Cornelia M. An, Ping de Andrade, Mariza Andrews, Jeanette S. Aspelund, Thor Atalay, Mustafa Aulchenko, Yurii Balkau, Beverley Bandinelli, Stefania Beckmann, Jacques S. Beilby, John P. Bellis, Claire Bergman, Richard N. Blangero, John Boban, Mladen Boehnke, Michael Boerwinkle, Eric Bonnycastle, Lori L. Boomsma, Dorret I. Borecki, Ingrid B. Boettcher, Yvonne Bouchard, Claude Brunner, Eric Budimir, Danijela Campbell, Harry Carlson, Olga Chines, Peter S. Clarke, Robert Collins, Francis S. Corbaton-Anchuelo, Arturo Couper, David de Faire, Ulf Dedoussis, George V. Deloukas, Panos Dimitriou, Maria Egan, Josephine M. Eiriksdottir, Gudny Erdos, Michael R. Eriksson, Johan G. Eury, Elodie Ferrucci, Luigi Ford, Ian Forouhi, Nita G. Fox, Caroline S. Franzosi, Maria Grazia Franks, Paul W. Frayling, Timothy M. Froguel, Philippe Galan, Pilar de Geus, Eco Gigante, Bruna Glazer, Nicole L. Goel, Anuj Groop, Leif Gudnason, Vilmundur Hallmans, Goeran Hamsten, Anders Hansson, Ola Harris, Tamara B. Hayward, Caroline Heath, Simon Hercberg, Serge Hicks, Andrew A. Hingorani, Aroon Hofman, Albert Hui, Jennie Hung, Joseph Jarvelin, Marjo-Riitta Jhun, Min A. Johnson, Paul C. D. Jukema, J. Wouter Jula, Antti Kao, W. H. Kaprio, Jaakko Kardia, Sharon L. R. Keinanen-Kiukaanniemi, Sirkka Kivimaki, Mika Kolcic, Ivana Kovacs, Peter Kumari, Meena Kuusisto, Johanna Kyvik, Kirsten Ohm Laakso, Markku Lakka, Timo Lannfelt, Lars Lathrop, G. Mark Launer, Lenore J. Leander, Karin Li, Guo Lind, Lars Lindstrom, Jaana Lobbens, Stephane Loos, Ruth J. F. Luan, Jian'an Lyssenko, Valeriya Magi, Reedik Magnusson, Patrik K. E. Marmot, Michael Meneton, Pierre Mohlke, Karen L. Mooser, Vincent Morken, Mario A. Miljkovic, Iva Narisu, Narisu O'Connell, Jeff Ong, Ken K. Oostra, Ben A. Palmer, Lyle J. Palotie, Aarno Pankow, James S. Peden, John F. Pedersen, Nancy L. Pehlic, Marina Peltonen, Leena Penninx, Brenda Pericic, Marijana Perola, Markus Perusse, Louis Peyser, Patricia A. Polasek, Ozren Pramstaller, Peter P. Province, Michael A. Raikkonen, Katri Rauramaa, Rainer Rehnberg, Emil Rice, Ken Rotter, Jerome I. Rudan, Igor Ruokonen, Aimo Saaristo, Timo Sabater-Lleal, Maria Salomaa, Veikko Savage, David B. Saxena, Richa Schwarz, Peter Seedorf, Udo Sennblad, Bengt Serrano-Rios, Manuel Shuldiner, Alan R. Sijbrands, Eric J. G. Siscovick, David S. Smit, Johannes H. Small, Kerrin S. Smith, Nicholas L. Smith, Albert Vernon Stancakova, Alena Stirrups, Kathleen Stumvoll, Michael Sun, Yan V. Swift, Amy J. Toenjes, Anke Tuomilehto, Jaakko Trompet, Stella Uitterlinden, Andre G. Uusitupa, Matti Vikstrom, Max Vitart, Veronique Vohl, Marie-Claude Voight, Benjamin F. Vollenweider, Peter Waeber, Gerard Waterworth, Dawn M. Watkins, Hugh Wheeler, Eleanor Widen, Elisabeth Wild, Sarah H. Willems, Sara M. Willemsen, Gonneke Wilson, James F. Witteman, Jacqueline C. M. Wright, Alan F. Yaghootkar, Hanieh Zelenika, Diana Zemunik, Tatijana Zgaga, Lina Wareham, Nicholas J. McCarthy, Mark I. Barroso, Ines Watanabe, Richard M. Florez, Jose C. Dupuis, Josee Meigs, James B. Langenberg, Claudia CA DIAGRAM Consortium MUTHER Consortium TI A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance SO NATURE GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; TYPE-2 DIABETES RISK; ASSOCIATION ANALYSIS; ENVIRONMENT INTERACTION; COMMON VARIANTS; LOCI; OBESITY; SUSCEPTIBILITY; GLUCOSE; POLYMORPHISM AB Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. C1 [Hivert, Marie-France; Grimsby, Jonna L.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Manning, Alisa K.; Chen, Han; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Manning, Alisa K.; Palotie, Aarno; Saxena, Richa; Voight, Benjamin F.; Florez, Jose C.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Manning, Alisa K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. 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[An, Ping; Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [de Andrade, Mariza] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Andrews, Jeanette S.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert Vernon] Iceland Heart Assoc, Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur; Smith, Albert Vernon] Univ Iceland, Reykjavik, Iceland. [Atalay, Mustafa; Lakka, Timo] Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland. [Balkau, Beverley] INSERM, Ctr Res Epidemiol & Populat Hlth, Ctr Rech Epidemiol & Sante Populat CESP, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. 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[Penninx, Brenda] Vrije Univ Amsterdam Med Ctr, Inst Res Extramural Med EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Pericic, Marijana] Inst Anthropol Res, Zagreb, Croatia. [Perusse, Louis] Univ Laval, Dept Prevent Med, Quebec City, PQ, Canada. [Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Rudan, Igor] Univ Split, Ctr Global Hlth, Split, Croatia. [Ruokonen, Aimo] Univ Oulu, Inst Clin Med, Oulu, Finland. [Saaristo, Timo] Finnish Diabet Assoc, Tampere, Finland. [Saaristo, Timo] Pirkanmaa Hosp Dist & Diabet Ctr, Tampere, Finland. [Savage, David B.; Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Saxena, Richa; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Schwarz, Peter] Univ Dresden, Dept Med, Div Prevent & Care Diabet, Dresden, Germany. [Seedorf, Udo] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Sijbrands, Eric J. G.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Siscovick, David S.; Smith, Nicholas L.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Div Endocrinol & Diabet, Dept Med, Leipzig, Germany. [Sun, Yan V.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tuomilehto, Jaakko] Hosp Univ La Paz, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Vohl, Marie-Claude] Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ, Canada. [Vollenweider, Peter; Waeber, Gerard] CHU Vaudois, Dept Internal Med, Lausanne, Switzerland. [Zgaga, Lina] Univ Zagreb, Dept Med Stat Epidemiol & Med Informat, Zagreb 41000, Croatia. [McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org; claudia.langenberg@mrc-epid.cam.ac.uk RI Leander, Karin/C-7261-2017; Boban, Mladen/E-2777-2017; Kolcic, Ivana/E-2713-2017; Hicks, Andrew/E-9518-2017; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Meitinger, Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Perusse, Louis/A-3444-2012; Bouchard, Claude/A-7637-2009; Smith, Albert/K-5150-2015; Kyvik, Kirsten /K-5680-2016; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Schwarz, Peter/B-5127-2013; Magnusson, Patrik/C-4458-2017; Aulchenko, Yurii/M-8270-2013; Altshuler, David/A-4476-2009; Lagou, Vasiliki/N-8451-2013; Corbaton-Anchuelo, Arturo/I-4390-2013; Pramstaller, Peter/C-2357-2008; Zondervan, Krina/M-1143-2013; Palmer, Lyle/K-3196-2014; Johnson, Paul/O-9695-2014; Hansson, Ola/F-1793-2011; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Li, Guo/E-5613-2012; Elliott, Amanda/G-5120-2012; Strawbridge, Rona/H-5422-2012; Rudan, Igor/I-1467-2012; Gigante, Bruna/I-9252-2012; Heath, Simon/J-4138-2012; Rice, Kenneth/A-4150-2013; Hui, Jennie/A-9543-2013; Deloukas, Panos/B-2922-2013; Beckmann, Jacques S /A-9772-2008; Aspelund, Thor/C-5983-2008; Colaus, PsyColaus/K-6607-2013 OI Kumari, Meena/0000-0001-9716-1035; Forouhi, Nita/0000-0002-5041-248X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Chen, Han/0000-0002-9510-4923; Navarro, Pau/0000-0001-5576-8584; Jorgensen, Torben/0000-0001-9453-2830; Watkins, Hugh/0000-0002-5287-9016; Small, Kerrin/0000-0003-4566-0005; Perola, Markus/0000-0003-4842-1667; Marmot, Michael/0000-0002-2431-6419; Hide, Winston/0000-0002-8621-3271; Zgaga, Lina/0000-0003-4089-9703; Lakka, Timo/0000-0002-9199-2871; Dupuis, Josee/0000-0003-2871-3603; Franks, Paul/0000-0002-0520-7604; Sijbrands, Eric/0000-0001-8857-7389; Miljkovic, Iva/0000-0002-3155-9777; Rybin, Denis/0000-0002-3657-4829; Barnes, Daniel/0000-0002-3781-7570; Kivimaki, Mika/0000-0002-4699-5627; Johnson, Toby/0000-0002-5998-3270; Leander, Karin/0000-0002-1404-9222; Kolcic, Ivana/0000-0001-7918-6052; Hicks, Andrew/0000-0001-6320-0411; Seedorf, Udo/0000-0003-4652-5358; Shungin, Dmitry/0000-0001-7900-5856; Zeggini, Eleftheria/0000-0003-4238-659X; Bouatia-Naji, Nabila/0000-0001-5424-2134; Magi, Reedik/0000-0002-2964-6011; van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; de Geus, Eco/0000-0001-6022-2666; Prokopenko, Inga/0000-0003-1624-7457; Smith, Albert/0000-0003-1942-5845; Kyvik, Kirsten /0000-0003-2981-0245; Hayward, Caroline/0000-0002-9405-9550; Schwarz, Peter/0000-0001-6317-7880; Sabater Lleal, Maria/0000-0002-0128-379X; Eriksson, Johan/0000-0002-2516-2060; Lahti, Jari/0000-0002-4310-5297; Kaprio, Jaakko/0000-0002-3716-2455; Pankow, James/0000-0001-7076-483X; Raikkonen, Katri/0000-0003-3124-3470; Aulchenko, Yurii/0000-0002-7899-1575; Altshuler, David/0000-0002-7250-4107; Corbaton-Anchuelo, Arturo/0000-0002-8775-4766; Zondervan, Krina/0000-0002-0275-9905; Palmer, Lyle/0000-0002-1628-3055; Johnson, Paul/0000-0001-6663-7520; Hansson, Ola/0000-0002-7394-7639; Gudnason, Vilmundur/0000-0001-5696-0084; Strawbridge, Rona/0000-0001-8506-3585; Rudan, Igor/0000-0001-6993-6884; Rice, Kenneth/0000-0001-5779-4495; Hui, Jennie/0000-0002-1653-2496; Deloukas, Panos/0000-0001-9251-070X; Beckmann, Jacques S /0000-0002-9741-1900; Aspelund, Thor/0000-0002-7998-5433; FU British Heart Foundation [RG/07/008/23674]; Chief Scientist Office [CZB/4/710]; Medical Research Council [G0902037, G0100222, G0701863, G0900339, G1002084, G19/35, G8802774, MC_PC_U127592696, MC_U106179471, MC_U106179472, MC_U127561128, MC_U127592696, MC_U137686857, MC_UP_A100_1003]; NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [S10 RR029392]; NHLBI NIH HHS [R01 HL105756]; NIDDK NIH HHS [K24 DK080140, P30 DK020572, P30 DK063491, R01 DK072193, R01 DK078616]; NIMH NIH HHS [R37 MH059490]; Wellcome Trust [090532, 091551] NR 79 TC 236 Z9 240 U1 8 U2 80 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 2012 VL 44 IS 6 BP 659 EP U81 DI 10.1038/ng.2274 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100012 PM 22581228 ER PT J AU Ellinor, PT Lunetta, KL Albert, CM Glazer, NL Ritchie, MD Smith, AV Arking, DE Muller-Nurasyid, M Krijthe, BP Lubitz, SA Bis, JC Chung, MK Doerr, M Ozaki, K Roberts, JD Smith, JG Pfeufer, A Sinner, MF Lohman, K Ding, JZ Smith, NL Smith, JD Rienstra, M Rice, KM Van Wagoner, DR Magnani, JW Wakili, R Clauss, S Rotter, JI Steinbeck, G Launer, LJ Davies, RW Borkovich, M Harris, TB Lin, HH Volker, U Volzke, H Milan, DJ Hofman, A Boerwinkle, E Chen, LY Soliman, EZ Voight, BF Li, G Chakravarti, A Kubo, M Tedrow, UB Rose, LM Ridker, PM Conen, D Tsunoda, T Furukawa, T Sotoodehnia, N Xu, SY Kamatani, N Levy, D Nakamura, Y Parvez, B Mahida, S Furie, KL Rosand, J Muhammad, R Psaty, BM Meitinger, T Perz, S Wichmann, HE Witteman, JCM Kao, WHL Kathiresan, S Roden, DM Uitterlinden, AG Rivadeneira, F McKnight, B Sjogren, M Newman, AB Liu, YM Gollob, MH Melander, O Tanaka, T Stricker, BHC Felix, SB Alonso, A Darbar, D Barnard, J Chasman, DI Heckbert, SR Benjamin, EJ Gudnason, V Kaab, S AF Ellinor, Patrick T. Lunetta, Kathryn L. Albert, Christine M. Glazer, Nicole L. Ritchie, Marylyn D. Smith, Albert V. Arking, Dan E. Mueller-Nurasyid, Martina Krijthe, Bouwe P. Lubitz, Steven A. Bis, Joshua C. Chung, Mina K. Doerr, Marcus Ozaki, Kouichi Roberts, Jason D. Smith, J. Gustav Pfeufer, Arne Sinner, Moritz F. Lohman, Kurt Ding, Jingzhong Smith, Nicholas L. Smith, Jonathan D. Rienstra, Michiel Rice, Kenneth M. Van Wagoner, David R. Magnani, Jared W. Wakili, Reza Clauss, Sebastian Rotter, Jerome I. Steinbeck, Gerhard Launer, Lenore J. Davies, Robert W. Borkovich, Matthew Harris, Tamara B. Lin, Honghuang Voelker, Uwe Voelzke, Henry Milan, David J. Hofman, Albert Boerwinkle, Eric Chen, Lin Y. Soliman, Elsayed Z. Voight, Benjamin F. Li, Guo Chakravarti, Aravinda Kubo, Michiaki Tedrow, Usha B. Rose, Lynda M. Ridker, Paul M. Conen, David Tsunoda, Tatsuhiko Furukawa, Tetsushi Sotoodehnia, Nona Xu, Siyan Kamatani, Naoyuki Levy, Daniel Nakamura, Yusuke Parvez, Babar Mahida, Saagar Furie, Karen L. Rosand, Jonathan Muhammad, Raafia Psaty, Bruce M. Meitinger, Thomas Perz, Siegfried Wichmann, H-Erich Witteman, Jacqueline C. M. Kao, W. H. Linda Kathiresan, Sekar Roden, Dan M. Uitterlinden, Andre G. Rivadeneira, Fernando McKnight, Barbara Sjogren, Marketa Newman, Anne B. Liu, Yongmei Gollob, Michael H. Melander, Olle Tanaka, Toshihiro Stricker, Bruno H. Ch Felix, Stephan B. Alonso, Alvaro Darbar, Dawood Barnard, John Chasman, Daniel I. Heckbert, Susan R. Benjamin, Emelia J. Gudnason, Vilmundur Kaeaeb, Stefan TI Meta-analysis identifies six new susceptibility loci for atrial fibrillation SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CHROMOSOME 4Q25; DILATED CARDIOMYOPATHY; PACEMAKER CHANNEL; COMMON VARIANTS; PR INTERVAL; CAVEOLIN-1; REPLICATION; MUTATIONS; PROTEINS AB Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules. C1 [Ellinor, Patrick T.; Lubitz, Steven A.; Sinner, Moritz F.; Rienstra, Michiel; Milan, David J.; Mahida, Saagar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Ellinor, Patrick T.; Milan, David J.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ellinor, Patrick T.; Albert, Christine M.; Tedrow, Usha B.; Ridker, Paul M.; Furie, Karen L.; Rosand, Jonathan; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA. [Lunetta, Kathryn L.; Xu, Siyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lunetta, Kathryn L.; Sinner, Moritz F.; Magnani, Jared W.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Lunetta, Kathryn L.; Sinner, Moritz F.; Magnani, Jared W.; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Albert, Christine M.; Lubitz, Steven A.; Tedrow, Usha B.; Rose, Lynda M.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Albert, Christine M.; Tedrow, Usha B.; Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Glazer, Nicole L.; Bis, Joshua C.; Smith, Nicholas L.; Li, Guo; Sotoodehnia, Nona; Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Mueller-Nurasyid, Martina; Sinner, Moritz F.; Wakili, Reza; Clauss, Sebastian; Steinbeck, Gerhard; Kaeaeb, Stefan] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina; Stricker, Bruno H. Ch] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Krijthe, Bouwe P.; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Chung, Mina K.; Smith, Jonathan D.; Van Wagoner, David R.] Cleveland Clin, Dept Cardiovasc Med, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Chung, Mina K.; Van Wagoner, David R.] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA. [Doerr, Marcus; Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Ozaki, Kouichi; Tanaka, Toshihiro] RIKEN Ctr Genom Med, Lab Cardiovasc Dis, Kanagawa, Japan. [Roberts, Jason D.; Borkovich, Matthew; Gollob, Michael H.] Univ Ottawa, Inst Heart, Arrhythmia Res Lab, Ottawa, ON, Canada. [Smith, J. Gustav] Lund Univ, Dept Cardiol, Lund, Sweden. [Smith, J. Gustav; Voight, Benjamin F.; Kathiresan, Sekar] Broad Inst Harvard & MIT, Cambridge, MA USA. [Pfeufer, Arne; Meitinger, Thomas] German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Lohman, Kurt] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Ding, Jingzhong] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Smith, Nicholas L.] Dept Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Smith, Nicholas L.; Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.; Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Jonathan D.] Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44106 USA. [Rienstra, Michiel] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands. [Rice, Kenneth M.; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Magnani, Jared W.; Lin, Honghuang; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, US NIH, Bethesda, MD 20892 USA. [Davies, Robert W.] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. [Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Chen, Lin Y.] Univ Minnesota, Sch Med, Dept Med, Cardiac Arrhythmia Ctr,Cardiovasc Div, Minneapolis, MN 55455 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA. [Kubo, Michiaki] RIKEN Ctr Genom Med, Lab Genotyping Dev, Kanagawa, Japan. [Conen, David] Univ Basel Hosp, Dept Med, CH-4031 Basel, Switzerland. [Tsunoda, Tatsuhiko] RIKEN Ctr Genom Med, Lab Med Informat, Kanagawa, Japan. [Furukawa, Tetsushi] Tokyo Med & Dent Univ, Med Res Inst, Dept Bioinformat Pharmacol, Tokyo, Japan. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Xu, Siyan; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Kamatani, Naoyuki] RIKEN Ctr Genom Med, Lab Stat Anal, Kanagawa, Japan. [Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan. [Parvez, Babar; Muhammad, Raafia; Roden, Dan M.; Darbar, Dawood] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Perz, Siegfried] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Neuherberg, Germany. [Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Kao, W. H. Linda] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Roden, Dan M.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. [Uitterlinden, Andre G.; Rivadeneira, Fernando; Stricker, Bruno H. Ch] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Sjogren, Marketa; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands. [Stricker, Bruno H. Ch] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Barnard, John] Cleveland Clin, Dept Quantitat Hlth Sci, Lerner Res Inst, Cleveland, OH 44106 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM pellinor@partners.org; skaab@med.uni-muenchen.de RI Alonso, Alvaro/A-4917-2010; Kaab, Stefan/H-3915-2012; Rice, Kenneth/A-4150-2013; Pfeufer, Arne/B-6634-2013; Ritchie, Marylyn/C-1114-2012; Van Wagoner, David/C-6783-2008; Wakili, Reza/F-1619-2014; Newman, Anne/C-6408-2013; Tsunoda, Tatsuhiko/K-2061-2014; Darbar, Dawood/C-9079-2015; Gudnason, Vilmundur/K-6885-2015; Li, Guo/E-5613-2012; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Tanaka, Toshihiro/J-9310-2014; Kubo, Michiaki/N-7947-2015; Smith, Albert Vernon/K-5150-2015; OI Alonso, Alvaro/0000-0002-2225-8323; Rice, Kenneth/0000-0001-5779-4495; Van Wagoner, David/0000-0001-8250-9828; Newman, Anne/0000-0002-0106-1150; Darbar, Dawood/0000-0002-4103-5977; Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira, Fernando/0000-0001-9435-9441; Tanaka, Toshihiro/0000-0001-6201-9784; Lunetta, Kathryn/0000-0002-9268-810X; Lin, Honghuang/0000-0003-3043-3942; Smith, Albert Vernon/0000-0003-1942-5845; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU NCATS NIH HHS [UL1 TR000124]; NHLBI NIH HHS [R01 HL105756, K24 HL105780, L30 HL097675, R01 HL090620, R01 HL092217, R01 HL092217-04, R01 HL104156, R21 HL106092, U19 HL065962, U19 HL065962-12]; NIDA NIH HHS [R21 DA027021] NR 30 TC 232 Z9 239 U1 2 U2 41 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 2012 VL 44 IS 6 BP 670 EP U88 DI 10.1038/ng.2261 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100013 PM 22544366 ER PT J AU Barbieri, CE Baca, SC Lawrence, MS Demichelis, F Blattner, M Theurillat, JP White, TA Stojanov, P Van Allen, E Stransky, N Nickerson, E Chae, SS Boysen, G Auclair, D Onofrio, RC Park, K Kitabayashi, N MacDonald, TY Sheikh, K Vuong, T Guiducci, C Cibulskis, K Sivachenko, A Carter, SL Saksena, G Voet, D Hussain, WM Ramos, AH Winckler, W Redman, MC Ardlie, K Tewari, AK Mosquera, JM Rupp, N Wild, PJ Moch, H Morrissey, C Nelson, PS Kantoff, PW Gabriel, SB Golub, TR Meyerson, M Lander, ES Getz, G Rubin, MA Garraway, LA AF Barbieri, Christopher E. Baca, Sylvan C. Lawrence, Michael S. Demichelis, Francesca Blattner, Mirjam Theurillat, Jean-Philippe White, Thomas A. Stojanov, Petar Van Allen, Eliezer Stransky, Nicolas Nickerson, Elizabeth Chae, Sung-Suk Boysen, Gunther Auclair, Daniel Onofrio, Robert C. Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Sheikh, Karen Vuong, Terry Guiducci, Candace Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Saksena, Gordon Voet, Douglas Hussain, Wasay M. Ramos, Alex H. Winckler, Wendy Redman, Michelle C. Ardlie, Kristin Tewari, Ashutosh K. Mosquera, Juan Miguel Rupp, Niels Wild, Peter J. Moch, Holger Morrissey, Colm Nelson, Peter S. Kantoff, Philip W. Gabriel, Stacey B. Golub, Todd R. Meyerson, Matthew Lander, Eric S. Getz, Gad Rubin, Mark A. Garraway, Levi A. TI Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer SO NATURE GENETICS LA English DT Article ID ETS GENE FUSIONS; FORKHEAD BOX A1; ANDROGEN RECEPTOR; SUPPRESSOR; CARCINOMA; PROTEIN; PROGRESSION; EXPRESSION; P27(KIP1); DATABASE AB Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year(1). Overtreatment of indolent disease also results in significant morbidity(2). Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21)(3,4) and PTEN (10q23)(5,6), gains of AR (the androgen receptor gene) 7,8 and fusion of ETS family transcription factor genes with androgen-responsive promoters(9-11). Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis(12,13) but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer. C1 [Barbieri, Christopher E.; Blattner, Mirjam; Chae, Sung-Suk; Boysen, Gunther; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y.; Sheikh, Karen; Vuong, Terry; Hussain, Wasay M.; Mosquera, Juan Miguel; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Barbieri, Christopher E.; Tewari, Ashutosh K.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Urol, New York, NY USA. [Baca, Sylvan C.; Lawrence, Michael S.; Theurillat, Jean-Philippe; Stojanov, Petar; Van Allen, Eliezer; Stransky, Nicolas; Nickerson, Elizabeth; Auclair, Daniel; Onofrio, Robert C.; Guiducci, Candace; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Winckler, Wendy; Redman, Michelle C.; Ardlie, Kristin; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Baca, Sylvan C.; Ramos, Alex H.; Kantoff, Philip W.; Meyerson, Matthew; Lander, Eric S.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA USA. [Baca, Sylvan C.; Van Allen, Eliezer; Kantoff, Philip W.; Meyerson, Matthew; Lander, Eric S.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Demichelis, Francesca; Hussain, Wasay M.] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA. [Demichelis, Francesca] Univ Trento, Ctr Integrat Biol, Trento, Italy. [White, Thomas A.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98104 USA. [Rupp, Niels; Wild, Peter J.; Moch, Holger] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland. [Morrissey, Colm; Nelson, Peter S.] Univ Washington, Dept Med, Seattle, WA USA. [Morrissey, Colm; Nelson, Peter S.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Golub, Todd R.; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. RP Rubin, MA (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. EM rubinma@med.cornell.edu; levi_garraway@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Van Allen, Eliezer/0000-0002-0201-4444; Barbieri, Christopher/0000-0002-0381-1947; Boysen, Gunther/0000-0002-7610-6085; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU US National Human Genome Research Institute (NHGRI) [U54 HG003067]; Kohlberg Foundation; Starr Cancer Consortium; Prostate Cancer Foundation; US Department of Defense [PC101020, PC093372]; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (US National Institutes of Health (NIH)) [P50 CA090381]; New Investigator Award [PC094516]; US National Cancer Institute, Early Detection Research Network [U01CA111275, NCI EDRN]; US National Cancer Institute [R01 CA125612]; Pacific Northwest Prostate Cancer SPORE [P50CA097186]; Swiss Science Foundation [PASMP3_134379/1]; US NIH [DP2OD002750] FX We are grateful for the assistance of members of the Broad Institute Biological Samples Platform, Genetic Analysis Platform and Genome Sequencing Platform. We thank S. Banerjee for computational assistance, R. Kim and R. Leung for their critical contributions to the Weill Cornell Prostate Cancer Tumor Bank, P. Schraml, S. Dettwiler and M. Storz for assistance with the University Hospital Zurich cohort and biobank and the members of the University of Washington Rapid Autopsy Program. We thank the University of Michigan Prostate Cancer Special Program of Research Excellence (SPORE) (K. Pienta) for sample contribution to this study. We are also grateful to the individuals with prostate cancer and the families who contributed to these studies. This work was supported by the US National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program (U54 HG003067 to the Broad Institute, E. S. L.), the Kohlberg Foundation (L. A. G.), the Starr Cancer Consortium (M. A. R., F. D. and L. A. G), the Prostate Cancer Foundation (M. A. R.), US Department of Defense Synergy Awards (PC101020 to F. D., L. A. G. and M. A. R. and PC093372 to T. W. and P.S.N.), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (US National Institutes of Health (NIH) P50 CA090381), a New Investigator Award (PC094516 to F. D.), the US National Cancer Institute, Early Detection Research Network (U01CA111275 and NCI EDRN to F. D. and M. A. R.), the US National Cancer Institute (R01 CA125612 to F. D. and M. A. R.), the Pacific Northwest Prostate Cancer SPORE (P50CA097186 to C. M. and P.S.N.), the Swiss Science Foundation (PASMP3_134379/1 to J.-P.T.) and a US NIH Director's New Innovator Award (DP2OD002750 to L. A. G.). S. C. B. is supported by a Medical Scientist Training Program (MSTP) grant from the US NIH. C. E. B. is supported by a Prostate Cancer Foundation Young Investigator Award. NR 54 TC 467 Z9 477 U1 9 U2 54 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 2012 VL 44 IS 6 BP 685 EP U107 DI 10.1038/ng.2279 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100016 PM 22610119 ER PT J AU Panizzi, JR Becker-Heck, A Castleman, VH Al-Mutairi, DA Liu, Y Loges, NT Pathak, N Austin-Tse, C Sheridan, E Schmidts, M Olbrich, H Werner, C Haffner, K Hellman, N Chodhari, R Gupta, A Kramer-Zucker, A Olale, F Burdine, RD Schier, AF O'Callaghan, C Chung, EMK Reinhardt, R Mitchison, HM King, SM Omran, H Drummond, IA AF Panizzi, Jennifer R. Becker-Heck, Anita Castleman, Victoria H. Al-Mutairi, Dalal A. Liu, Yan Loges, Niki T. Pathak, Narendra Austin-Tse, Christina Sheridan, Eamonn Schmidts, Miriam Olbrich, Heike Werner, Claudius Haeffner, Karsten Hellman, Nathan Chodhari, Rahul Gupta, Amar Kramer-Zucker, Albrecht Olale, Felix Burdine, Rebecca D. Schier, Alexander F. O'Callaghan, Christopher Chung, Eddie M. K. Reinhardt, Richard Mitchison, Hannah M. King, Stephen M. Omran, Heymut Drummond, Iain A. TI CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms SO NATURE GENETICS LA English DT Article ID RIGHT AXIS FORMATION; ZEBRAFISH PRONEPHROS; PROTEIN; REQUIREMENT; EXPRESSION; ENCODES; EMBRYOS; GENES AB Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality(1). Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1: 15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending(2). Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci(3). Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated. C1 [Panizzi, Jennifer R.; Liu, Yan; Pathak, Narendra; Hellman, Nathan; Gupta, Amar; Drummond, Iain A.] Massachusetts Gen Hosp, Div Neurol, Charlestown, MA 02129 USA. [Panizzi, Jennifer R.; Pathak, Narendra; Hellman, Nathan; Drummond, Iain A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Becker-Heck, Anita] Univ Hosp Freiburg, Dept Pediat, Freiburg, Germany. [Becker-Heck, Anita; Loges, Niki T.; Olbrich, Heike; Werner, Claudius; Omran, Heymut] Univ Klinikum Munster, Klin & Poliklin Kinder & Jugendmed Allgemeine Pae, Munster, Germany. [Castleman, Victoria H.] UCL, Mol Med Unit, Inst Child Hlth, London, England. [Al-Mutairi, Dalal A.; Sheridan, Eamonn] St James Univ Hosp, Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Al-Mutairi, Dalal A.] Kuwait Univ, Fac Med, Dept Pathol, Kuwait, Kuwait. [Austin-Tse, Christina] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Chodhari, Rahul; Chung, Eddie M. K.] UCL, Inst Child Hlth, Gen & Adolescent Paediat Unit, London, England. [Kramer-Zucker, Albrecht] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Olale, Felix] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA. [Burdine, Rebecca D.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Schier, Alexander F.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. [O'Callaghan, Christopher] Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England. [Reinhardt, Richard] Max Planck Inst Plant Breeding Res, Genome Ctr Cologne, Cologne, Germany. [King, Stephen M.] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Neurol, Charlestown, MA 02129 USA. EM king@neuron.uchc.edu; heymut.omran@ukmuenster.de; idrummon@receptor.mgh.harvard.edu RI Schmidts, Miriam/A-3777-2012; OI Schmidts, Miriam/0000-0002-1714-6749; Austin-Tse, Christina/0000-0001-6492-6716; Burdine, Rebecca/0000-0001-6620-5015 FU PCD Family Support Group (UK); German patient support group 'Kartagener Syndrom und Primaere Ciliaere Dyskinesie e.V.'; US National Institutes of Health [DK053093, GM051293]; National Research Service Award [F32DK083868]; American Heart Association; Deutsche Forschungsgemeinschaft (DFG) [DFG Om 6/4, GRK1109, SFB592]; EU; IZKF [Om2/009/12]; Kindness for Kids grant; Medical Research Council UK; Wellcome Trust; Fondation Milena Carvajal-ProKartagener FX We thank the patients and their families for their participation and acknowledge support from the PCD Family Support Group (UK) and the German patient support group 'Kartagener Syndrom und Primaere Ciliaere Dyskinesie e.V.'. We thank R. Mark Gardiner and E. Moya for their help and involvement in the study. We thank R. Hirst and A. Rutman for electron microscopy. We thank A. Heer, C. Warmt, D. Nergenau, R. S. Patel-King and L. Luo for excellent technical assistance. This work was funded by US National Institutes of Health grants DK053093 (I. A. D.) and GM051293 (S. M. K.), National Research Service Award fellowship grant F32DK083868 (J.R.P.), an American Heart Association Established Investigator Award (A. F. S.), Deutsche Forschungsgemeinschaft (DFG) grants (DFG Om 6/4, GRK1109 and SFB592), EU grant SYSCILIA, IZKF-project (Om2/009/12), and Kindness for Kids grant (H. Omran), the Medical Research Council UK, the Wellcome Trust and the Fondation Milena Carvajal-ProKartagener. NR 28 TC 78 Z9 85 U1 2 U2 15 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 2012 VL 44 IS 6 BP 714 EP U148 DI 10.1038/ng.2277 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 949BT UT WOS:000304551100022 PM 22581229 ER PT J AU Prohaska, R Sibon, OCM Rudnicki, DD Danek, A Hayflick, SJ Verhaag, EM Vonk, JJ Margolis, RL Walker, RH AF Prohaska, Rainer Sibon, Ody C. M. Rudnicki, Dobrila D. Danek, Adrian Hayflick, Susan J. Verhaag, Esther M. Vonk, Jan J. Margolis, Russell L. Walker, Ruth H. TI Brain, blood, and iron: Perspectives on the roles of erythrocytes and iron in neurodegeneration SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Neuroacanthocytosis; Neurodegeneration; Iron; NBIA ID KINASE-ASSOCIATED NEURODEGENERATION; INFANTILE NEUROAXONAL DYSTROPHY; INDEPENDENT PHOSPHOLIPASE A(2); HALLERVORDEN-SPATZ-SYNDROME; DISEASE-LIKE 2; DOMINANT CHOREA-ACANTHOCYTOSIS; LIGHT-POLYPEPTIDE GENE; KELL-NULL PHENOTYPE; MCLEOD-SYNDROME; HUNTINGTONS-DISEASE AB The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly rare and challenging to study. The NBIA disorders are defined by their appearance on brain magnetic resonance imaging, with iron deposition in the basal ganglia. Clinical features vary, but most include a movement disorder. New causative genes are being rapidly identified; however, the mechanisms by which mutations cause iron accumulation and neurodegeneration are not well understood. NA syndromes are also characterized by a progressive movement disorder, accompanied by cognitive and psychiatric features, resulting from mutations in a number of genes whose roles are also basically unknown. An overlapping feature of the two groups, NBIA and NA, is the occurrence of acanthocytes, spiky red cells with a poorly-understood membrane dysfunction. In this review we summarise recent developments in this field, specifically insights into cellular mechanisms and from animal models. Cell membrane research may shed light upon the significance of the erythrocyte abnormality, and upon possible connections between the two sets of disorders. Shared pathophysiologic mechanisms may lead to progress in the understanding of other types of neurodegeneration. Published by Elsevier Inc. C1 [Walker, Ruth H.] James P Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Prohaska, Rainer] Med Univ Vienna, Max F Perutz Labs, Vienna, Austria. [Sibon, Ody C. M.; Verhaag, Esther M.; Vonk, Jan J.] Univ Groningen, Sect Radiat & Stress Cell Biol, Dept Cell Biol, Univ Med Ctr Groningen, Groningen, Netherlands. [Rudnicki, Dobrila D.; Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol,Lab Genet Neurobiol, Baltimore, MD 21205 USA. [Danek, Adrian] Univ Munich, Neurol Klin & Poliklin, Munich, Germany. [Hayflick, Susan J.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Hayflick, Susan J.] Oregon Hlth & Sci Univ, Dept Pediat & Neurol, Portland, OR 97201 USA. [Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD USA. RP Walker, RH (reprint author), James P Peters Vet Affairs Med Ctr, Dept Neurol 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu RI Danek, Adrian/G-7339-2011 OI Danek, Adrian/0000-0001-8857-5383 FU National Institute of Neurological Diseases and Stroke; Office of Rare Diseases Research; National Institute of Child Health and Human Development [1R13NS067922-01]; Movement Disorder Society; Advocacy for Neuroacanthocytosis Patients (UK); Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) (Italy); NBIA Disorders Association (USA); Hoffnungsbaum e.V. (Germany); GlaxoSmithKline; European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA) [01GM1003]; RP (FWF) [I 438-B13]; OCMS (ZonMW) [113301162] FX This article reflects presentations and discussion at a meeting entitled "Brain, Blood and Iron: Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation" which was held in Bethesda, MD, USA on Oct 1-2 2010. This meeting was supported by the National Institute of Neurological Diseases and Stroke; the Office of Rare Diseases Research, and the National Institute of Child Health and Human Development [1R13NS067922-01], and also by the Movement Disorder Society, Advocacy for Neuroacanthocytosis Patients (UK), Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) (Italy), NBIA Disorders Association (USA), Hoffnungsbaum e.V. (Germany) and GlaxoSmithKline. Funding by an ERA-Net E-Rare project, "European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA)", is gratefully acknowledged by AD (BMBF/DLR grant 01GM1003), RP (FWF grant I 438-B13), and OCMS (ZonMW grant 113301162). NR 228 TC 22 Z9 23 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 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2012 VL 46 IS 3 BP 607 EP 624 DI 10.1016/j.nbd.2012.03.006 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 950DK UT WOS:000304629300011 PM 22426390 ER PT J AU Madan, A Archambeau, OG Milsom, VA Goldman, RL Borckardt, JJ Grubaugh, AL Tuerk, PW Frueh, BC AF Madan, Alok Archambeau, Olga G. Milsom, Vanessa A. Goldman, Rachel L. Borckardt, Jeffery J. Grubaugh, Anouk L. Tuerk, Peter W. Frueh, B. Christopher TI More Than Black and White: Differences in Predictors of Obesity Among Native Hawaiian/Pacific Islanders and European Americans SO OBESITY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; PACIFIC ISLANDERS; YOUNG-ADULTS; RISK-FACTORS; WEIGHT; HAWAIIANS; DISORDER; MINI AB Although Native Hawaiians and Pacific Islanders exhibit the highest rates of obesity and associated chronic diseases of any racial/ethnic group, they remain vastly underrepresented in health research. In a cross-sectional survey of college students (N = 402) we examined BMI and health outcomes in an ethno-racially diverse rural sample of Native Hawaiian/Pacific Islanders (25.1%), Asian Americans (39.8%), and European Americans (35.1%). Measures assessed BMI, health status, health behaviors, frequency of exercise, and symptoms of psychiatric disorders (i.e., depression, anxiety, posttraumatic stress, and substance abuse and dependence). Regression analyses revealed that an overall model of five predictors (gender, race, regular exercise, difficulty sleeping, and anxiety) was significantly associated with obesity (P < 0.001) and correctly classified 84.2% of cases. A 30.7% of Native Hawaiians/Pacific Islanders were obese as compared with 9.2% of European Americans and 10.6% of Asian Americans. These findings suggest that Native Hawaiian/Pacific Islanders are at high risk for obesity and associated medical comorbidities, but that regular physical activity may ameliorate this risk. Further, these results support the consideration of Native Hawaiians/Pacific Islanders as a distinct racial/ethnic subgroup separate from other Asian populations. C1 [Madan, Alok; Goldman, Rachel L.; Borckardt, Jeffery J.; Grubaugh, Anouk L.; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Archambeau, Olga G.; Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Milsom, Vanessa A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Grubaugh, Anouk L.; Tuerk, Peter W.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Madan, A (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM madana@musc.edu OI Goldman, Rachel/0000-0001-6147-3934 FU National Institute of Mental Health [MH074468]; McNair Foundation FX This work was partially supported by the grant MH074468 from the National Institute of Mental Health, and from the McNair Foundation. Elements of the current work were included in O.G.A.'s master's thesis. NR 18 TC 5 Z9 5 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JUN PY 2012 VL 20 IS 6 BP 1325 EP 1328 DI 10.1038/oby.2012.15 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 948QO UT WOS:000304517900034 PM 22286530 ER PT J AU Mai, CL Cote, CJ AF Mai, Christine L. Cote, Charles J. TI A history of pediatric anesthesia: a tale of pioneers and equipment SO PEDIATRIC ANESTHESIA LA English DT Review DE history; equipment; critical care; developing world; airway devices equipment; monitors equipment ID MEASURING CARDIAC-OUTPUT; BISPECTRAL INDEX; PULSE OXIMETRY; CEREBRAL OXIMETRY; ELECTRICAL VELOCIMETRY; REGIONAL ANESTHESIA; VIDEO LARYNGOSCOPE; VEIN CANNULATION; LARYNGEAL MASK; CARBON-DIOXIDE AB The history of pediatric anesthesia is fascinating in terms of how inventive anesthesiologists became over time to address the needs for advances in surgery. We have many pioneers and heroes. We hope you will enjoy this brief overview and that we have not left out any of the early contributors to our speciality. Obviously there is insufficient space to include everyone. C1 [Mai, Christine L.; Cote, Charles J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,MassGen Hosp, Boston, MA 02114 USA. RP Mai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,MassGen Hosp, Boston, MA 02114 USA. EM cmai1@partners.org NR 83 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JUN PY 2012 VL 22 IS 6 BP 511 EP 520 DI 10.1111/j.1460-9592.2012.03828.x PG 10 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 943PP UT WOS:000304137100002 PM 22443224 ER PT J AU Maples, NJ Copeland, LA Zeber, JE Li, XY Moore, TA Dassori, A Velligan, DI Miller, AL AF Maples, Natalie J. Copeland, Laurel Anne Zeber, John E. Li, Xueying Moore, Troy A. Dassori, Albana Velligan, Dawn Irene Miller, Alexander L. TI Can Medication Management Coordinators Help Improve Continuity of Care After Psychiatric Hospitalization? SO PSYCHIATRIC SERVICES LA English DT Article ID ALGORITHM PROJECT; MENTAL-ILLNESS; RISK-FACTORS; SCHIZOPHRENIA; REHOSPITALIZATION; PATIENT; IMPLEMENTATION; INDIVIDUALS; STRATEGIES; DISORDER AB Objective: This demonstration project examined whether medication management coordinators enhanced continuity of care from inpatient facilities to an outpatient public mental health clinic. Methods: From 2004 to 2008, patients (N=325) hospitalized with schizophrenia or schizoaffeetive or bipolar disorder enrolled in a medication management program before discharge or at their first clinic appointment. Medication management coordinators supplemented existing clinic practices by identifying recently hospitalized patients, providing inpatient and outpatient prescribing clinicians with patients' complete medication history, meeting with patients for six months postdischarge to assess clinical status and provide medication education, and advocating guideline-concordant prescribing. Recently discharged patients (N=345) assigned to a different outpatient clinic within the same agency served as the comparison group. Intent-to-treat, repeated-measures analyses for mixed models compared the groups' number of hospital admissions, hospital days, and medication appointments kept and use of nurse or case manager contact hours and emergency or crisis services during the 12 months before enrollment, the six-month intervention, and the six-month follow-up period. Results: After discharge, individuals enrolled in medication management were more likely than comparison patients to attend outpatient appointments, and they had more medication visits and nurse or case manager treatment hours than the comparison group. Use of hospital and crisis or emergency services by all patients decreased. Almost one-third of patients never attended an outpatient appointment after hospital discharge. Conclusions: Although this program succeeded in improving continuity of care, additional interventions may be required to reduce rehospitalization and crisis care. (Psychiatric Services 63:554-560, 2012; doi: 10.1176/appi.ps.201100264) C1 [Maples, Natalie J.; Li, Xueying; Moore, Troy A.; Velligan, Dawn Irene; Miller, Alexander L.] UT Hlth Sci Ctr San Antonio, Div Schizophrenia & Related Disorders, Dept Psychiat, San Antonio, TX 78229 USA. [Copeland, Laurel Anne; Zeber, John E.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX USA. [Copeland, Laurel Anne; Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Dassori, Albana] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Maples, NJ (reprint author), UT Hlth Sci Ctr San Antonio, Div Schizophrenia & Related Disorders, Dept Psychiat, 7703 Floyd Curl Dr,MS 7797, San Antonio, TX 78229 USA. EM maplesn@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 FU AstraZeneca; U.S. Veterans Health Administration; UT Health Science Center San Antonio; Scott & White Healthcare; GlaxoSmithKline; Pfizer FX This demonstration project was funded by AstraZeneca through a grant to the National Center for Behavioral Health Care Solutions, a 501(c)3 organization affiliated with the Center for Health Care Services. Additional support was provided by the U.S. Veterans Health Administration, the UT Health Science Center San Antonio, and Scott & White Healthcare. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the U.S. government.; Dr. Zeber received a research grant in 2011-2012 from GlaxoSmithKline as principal investigator for one site of a multisite study unrelated to this article. Dr. Velligan is a consultant for or on the advisory boards of Ortho-McNeil Janssen Pharmaceuticals, Teva Pharmaceuticals, AstraZeneca Pharmaceuticals, Roche Genentech, Abbott Pharmaceuticals, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Bristol-Myers Squibb, Amgen, and Merck and Shire Pharmaceuticals. Dr. Miller is a member of the data monitoring committee for Otsuka and was on the advisory board of Myriad RBM in 2010. He has received investigator-initiated grant funding from Pfizer. The other authors report no competing interests. NR 25 TC 4 Z9 4 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2012 VL 63 IS 6 BP 554 EP 560 DI 10.1176/appi.ps.201100264 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 949IE UT WOS:000304569100007 PM 22476107 ER PT J AU Walling, SM Suvak, MK Howard, JM Taft, CT Murphy, CM AF Walling, Sherry Muterspaugh Suvak, Michael K. Howard, Jamie M. Taft, Casey T. Murphy, Christopher M. TI Race/Ethnicity as a Predictor of Change in Working Alliance During Cognitive Behavioral Therapy for Intimate Partner Violence Perpetrators SO PSYCHOTHERAPY LA English DT Article DE working alliance; race; ethnicity; intimate partner violence; group treatment ID INDIVIDUAL PSYCHOTHERAPY; HISPANIC COUPLES; REGRESSION; VARIABLES; CLIENTS; BLACK; WHITE; MEN; ATTENDANCE; PATTERNS AB Despite evidence that the working alliance (WA) is an important factor in psychotherapy outcome and that race/ethnicity plays an important role in the processes of therapy, few studies have directly examined associations between WA and race/ethnicity. These relationships may be particularly salient for difficult-to-engage populations, such as men participating in treatment for intimate partner violence. The current study examined WA ratings in a sample of 107 male intimate partner violence perpetrators attending a 16-week cognitive-behavioral group program. Approximately 50% of these participants were Caucasian and 50% were members of a racial/ethnic minority group (African American, Asian American, Hispanic, and American Indian). Growth curve modeling was used to assess changes in both therapist and client WA ratings across four time points during therapy. Findings indicated that there was no mean level of change in therapist WA ratings over time. However, clients' WA ratings demonstrated a reliable, steady increase across sessions. A significant interaction between WA and race/ethnicity emerged such that Caucasian participants reported a significant increase in WA over time, whereas members of racial/ethnic minority group did not report a consistent pattern of change. The interaction between client race/ethnicity and WA was also a significant predictor of treatment outcome at 6-month follow-up. C1 [Walling, Sherry Muterspaugh] Fresno Pacific Univ, Dept Psychol, Fresno, CA 93702 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA USA. [Howard, Jamie M.; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Howard, Jamie M.; Taft, Casey T.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Murphy, Christopher M.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Walling, SM (reprint author), Fresno Pacific Univ, Dept Psychol, 1717 S Chestnut Ave, Fresno, CA 93702 USA. EM sherry.walling@fresno.edu FU NIMH NIH HHS [1R03MH56373, 1F31MH12234] NR 47 TC 9 Z9 9 U1 1 U2 11 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD JUN PY 2012 VL 49 IS 2 BP 180 EP 189 DI 10.1037/a0025751 PG 10 WC Psychology, Clinical SC Psychology GA 951TH UT WOS:000304742400012 PM 22181028 ER PT J AU Gellis, LA AF Gellis, Les A. TI An Investigation of a Cognitive Refocusing Technique To Improve Sleep SO PSYCHOTHERAPY LA English DT Article DE insomnia; cognitive therapy; behavior therapy; sleep ID CHRONIC INSOMNIA; VALIDATION; THOUGHTS; INDEX AB Developing techniques designed to minimize arousing cognitions during the evening may be important to help improve the treatment of insomnia. This investigation assessed an intervention that focused exclusively on enhancing cognitive refocusing at sleep onset to change the content and style of presleep cognitions in order to improve sleep. Individuals with primary insomnia (N = 10; 90% male, mean age = 49.2, SD = 12.6) attended four weekly individual meetings. Sleep quality (the Pittsburgh Sleep Quality Index), insomnia severity (the Insomnia Severity Index), sleep parameters based on one week of sleep diaries, and arousing thought content, were compared at baseline, posttreatment, and at a 1-month follow-up. Adherence was high, and participants showed good ability to engage in the procedure. Significant improvements in sleep quality, insomnia severity, sleep onset latency, total sleep time, and arousing thought content were revealed. Large effect sizes were observed on the majority of sleep variables at follow-up. Preliminary results were encouraging regarding a technique that targets the refocusing of thoughts during the evening in order to improve sleep. Further study regarding the efficacy of this procedure is warranted. C1 [Gellis, Les A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Gellis, LA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. EM lesgellis@gmail.com NR 24 TC 3 Z9 3 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD JUN PY 2012 VL 49 IS 2 BP 251 EP 257 DI 10.1037/a0025746 PG 7 WC Psychology, Clinical SC Psychology GA 951TH UT WOS:000304742400018 PM 22309052 ER PT J AU Eisenberg, JD Harvey, HB Moore, DA Gazelle, GS Pandharipande, PV AF Eisenberg, Jonathan D. Harvey, H. Benjamin Moore, Donald A. Gazelle, G. Scott Pandharipande, Pari V. TI Falling Prey to the Sunk Cost Bias: A Potential Harm of Patient Radiation Dose Histories SO RADIOLOGY LA English DT Editorial Material C1 [Eisenberg, Jonathan D.; Gazelle, G. Scott; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Eisenberg, Jonathan D.; Harvey, H. Benjamin; Gazelle, G. Scott; Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Harvey, H. Benjamin; Gazelle, G. Scott; Pandharipande, Pari V.] Harvard Univ, Sch Med, Boston, MA USA. [Moore, Donald A.] Univ Calif Berkeley, Haas Sch Business, Berkeley, CA 94720 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org FU NCI NIH HHS [K07CA133097, K07 CA133097] NR 18 TC 20 Z9 20 U1 0 U2 3 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 2012 VL 263 IS 3 BP 626 EP 628 DI 10.1148/radiol.12112459 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947GK UT WOS:000304416900002 PM 22623688 ER PT J AU Cronin, CG Prakash, P Daniels, GH Boland, GW Kalra, MK Halpern, EF Palmer, EL Blake, MA AF Cronin, Carmel G. Prakash, Priyanka Daniels, Gilbert H. Boland, Giles W. Kalra, Mannudeep K. Halpern, Elkan F. Palmer, Edwin L. Blake, Michael A. TI Brown Fat at PET/CT: Correlation with Patient Characteristics SO RADIOLOGY LA English DT Article ID ADIPOSE-TISSUE; MALIGNANT-LYMPHOMA; F-18-FDG PET/CT; USA-FAT; PREVALENCE; PATTERNS; PITFALLS; CT AB Purposes: To assess the prevalence of brown fat in patients with cancer, compare demographic characteristics of those with and those without brown fat, and correlate these characteristics with the mean and maximum standardized uptake values of brown fat. Materials and Methods: This case-control study was institutional review board approved and HIPAA compliant. Informed consent was waived. Reports of 12 195 consecutive positron emission tomography/computed tomography examinations performed in 6867 patients between January 2004 and November 2008 were reviewed for documented fluorodeoxyglucose (FDG) uptake in brown fat (n = 298). Control patients (n = 298) without brown fat were chosen and matched for age, sex, and month and year of examination. Age, sex, weight, body mass index, ethnicity, and examination stage (initial vs restaging) were compared between groups. Paired Student t test, chi(2) test, Pearson correlation coefficient, and analysis of variance were used for statistical analysis. Results: Uptake of FDG in brown fat was demonstrated in 298 of 6867 (4.33%) patients. Prevalence of brown fat was significantly higher in female (5.9% [211 of 3587]) than in male patients (2.65% [87 of 3280]; P < .001). Those with brown fat had significantly lower body weight (147.5 lb +/- 3.8 vs 168.61 lb +/- 5.0; P < .001) and body mass index (24.3 +/- 0.54 vs 27.6 +/- 0.77; P < .001) than control patients. There was no significant difference in the prevalence of brown fat among ethnic groups. The maximum standardized uptake value of brown fat had a significant inverse correlation with age (r = -0.3, P < .001). Conclusion: Patients with brown fat were more likely to be female and thinner than those without brown fat. Younger patients were more likely to have higher maximum standardized uptake values of brown fat. (c) RSNA, 2012 C1 [Cronin, Carmel G.; Prakash, Priyanka; Daniels, Gilbert H.; Boland, Giles W.; Kalra, Mannudeep K.; Halpern, Elkan F.; Palmer, Edwin L.; Blake, Michael A.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Cronin, CG (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM cgcronin@partners.org FU GE Healthcare FX C.G.C. No potential conflicts of interest to disclose. P.P. No potential conflicts of interest to disclose. G.D. No potential conflicts of interest to disclose. G.B. No potential conflicts of interest to disclose. M.K. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: Payment for development of educational presentations and board membership for GE Healthcare. Institution has grants or grants pending from GE Healthcare. E.H. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: Consultancy with Hologic. E.P. No potential conflicts of interest to disclose. M.B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received book editing royalties from Springer Verlag. NR 17 TC 19 Z9 21 U1 0 U2 5 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 2012 VL 263 IS 3 BP 836 EP 842 DI 10.1148/radiol.12100683 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 947GK UT WOS:000304416900026 PM 22623697 ER PT J AU Rao, RC Choudhry, N Gragoudas, ES AF Rao, Rajesh C. Choudhry, Netan Gragoudas, Evangelos S. TI Enhanced Depth Imaging Spectral-Domain Optical Coherence Tomography Findings in Sclerochoroidal Calcification SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Editorial Material DE enhanced depth imaging; optical coherence tomography; sclerochoroidal calcification C1 [Choudhry, Netan; Gragoudas, Evangelos S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. [Rao, Rajesh C.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. RP Gragoudas, ES (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM evangelos_gragoudas@meei.harvard.edu OI Rao, Rajesh/0000-0002-5776-8366 NR 4 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUN PY 2012 VL 32 IS 6 BP 1226 EP 1227 DI 10.1097/IAE.0b013e3182576e50 PG 2 WC Ophthalmology SC Ophthalmology GA 948VY UT WOS:000304532100024 PM 22572772 ER PT J AU Rosenbaum, JT Ku, J Ali, A Choi, D Suhler, EB AF Rosenbaum, James T. Ku, Jennifer Ali, Amro Choi, Dongseok Suhler, Eric B. TI Patients with Retinal Vasculitis Rarely Suffer from Systemic Vasculitis SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE retinal vasculitis; vasculitis; Behcet's; granulomatosis with polyangiitis; polyarteritis nodosa ID POLYARTERITIS-NODOSA; WEGENERS GRANULOMATOSIS; OCULAR MANIFESTATIONS; DISEASE; COMPLICATIONS; UVEITIS AB Objectives: Systemic vasculitis is often mistakenly assumed to be a common cause of retinal vasculitis. We sought to determine the relationship between retinal vasculitis and systemic vasculitis. Methods: A selected review was performed on 1390 charts of patients attending the uveitis clinic at the Oregon Health and Science University between 1985 and 2010. Included in the review were all patients with diagnoses commonly associated with retinal vasculitis and all patients who were diagnosed with a systemic vasculitis. Retinal vasculitis was identified by perivascular exudates, intraretinal hemorrhage, or cotton wool spots as seen on clinical examination or by vascular occlusion or leakage as identified by fluorescein angiogram. Results: Two hundred seven or 14.9% of patients with uveitis had retinal vasculitis as a component of the intraocular inflammation. Thirty-five patients had retinal vasculitis that was primary, ie, not associated with a systemic disease, and the dominant manifestation of the uveitis. Fourteen of the patients with retinal vasculitis had Behcet's disease. Only 11 of the 1390 patients with uveitis had a systemic vasculitis. Of these 11, four had retinal vasculitis including 1 secondary to a cytomegalovirus retinitis. Thus, systemic vasculitis was directly responsible for 1.4% or 3 of 207 cases of retinal vasculitis. Nonvasculitic systemic diseases such as sarcoidosis (n = 13), syndromes confined to the eye such as pars planitis (n = 36), and intraocular infections (n = 29) were far more common causes of retinal vasculitis. Conclusions: Retinal vasculitis is a relatively common feature of uveitis. Patients with retinal vasculitis, however, rarely suffer from 1 of the classical systemic vasculitides. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:859-865 C1 [Rosenbaum, James T.; Ali, Amro; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Ku, Jennifer; Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth, Portland, OR 97239 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Rosenbaum, JT (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, 3181 SW Sam Jackson Pk Rd,L467Ad, Portland, OR 97239 USA. EM rosenbaj@ohsu.edu FU Research to Prevent Blindness; William C. Kuzell Foundation; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation FX This work was supported by Research to Prevent Blindness, the William C. Kuzell Foundation, the Stan and Madelle Rosenfeld Family Trust, and the William and Mary Bauman Foundation. NR 24 TC 11 Z9 11 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 2012 VL 41 IS 6 BP 859 EP 865 DI 10.1016/j.semarthrit.2011.10.006 PG 7 WC Rheumatology SC Rheumatology GA 950XL UT WOS:000304685100012 PM 22177107 ER PT J AU Avigan, D Rosenblatt, J Kufe, D AF Avigan, David Rosenblatt, Jacalyn Kufe, Donald TI Dendritic/Tumor Fusion Cells as Cancer Vaccines SO SEMINARS IN ONCOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; COLONY-STIMULATING FACTOR; ALLOGENEIC HEPATOCELLULAR-CARCINOMA; BONE-MARROW-TRANSPLANTATION; ANTIGEN-LOADING STRATEGIES; AUTOLOGOUS TUMOR-CELLS; ANTITUMOR IMMUNITY; MULTIPLE-MYELOMA; SUPPRESSOR-CELLS; PERIPHERAL-BLOOD C1 [Avigan, David; Rosenblatt, Jacalyn] Beth Israel Deaconess Med Ctr, Hematol Malignancies Bone Marrow Transplant Progr, Div Hematol Oncol, Boston, MA 02215 USA. [Kufe, Donald] Dana Farber Canc Inst, Translat Pharmacol & Early Therapeut Trials Progr, Dept Med Oncol, Boston, MA 02115 USA. RP Avigan, D (reprint author), Beth Israel Deaconess Med Ctr, Hematol Malignancies Bone Marrow Transplant Progr, Div Hematol Oncol, 330 Brookline Ave,Mailstop KS 121, Boston, MA 02215 USA. EM davigan@bidmc.harvard.edu FU NCI NIH HHS [P01 CA078378, P01 CA155258] NR 99 TC 16 Z9 20 U1 1 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2012 VL 39 IS 3 BP 287 EP 295 DI 10.1053/j.seminoncol.2012.02.003 PG 9 WC Oncology SC Oncology GA 948KW UT WOS:000304503100006 PM 22595051 ER PT J AU Tsai, AC Bangsberg, DR Frongillo, EA Hunt, PW Muzoora, C Martin, JN Weiser, SD AF Tsai, Alexander C. Bangsberg, David R. Frongillo, Edward A. Hunt, Peter W. Muzoora, Conrad Martin, Jeffrey N. Weiser, Sheri D. TI Food insecurity, depression and the modifying role of social support among people living with HIV/AIDS in rural Uganda SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE AIDS/HIV; International health; Social support; Food; Food insecurity; Depression; Uganda ID HIV-INFECTED INDIVIDUALS; ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; HOST-RESISTANCE; POSITIVE WOMEN; MENTAL-HEALTH; BURKINA-FASO; SYMPTOMS; STRESS; ASSOCIATION AB Depression is common among people living with HIV/AIDS and contributes to a wide range of worsened HIV-related outcomes, including AIDS-related mortality. Targeting modifiable causes of depression, either through primary or secondary prevention, may reduce suffering as well as improve HIV-related outcomes. Food insecurity is a pervasive source of uncertainty for those living in resource-limited settings, and cross-sectional studies have increasingly recognized it as a critical determinant of poor mental health. Using cohort data from 456 men and women living with HIV/AIDS initiating HIV antiretroviral therapy in rural Uganda, we sought to (a) estimate the association between food insecurity and depression symptom severity, (b) assess the extent to which social support may serve as a buffer against the adverse effects of food insecurity, and (c) determine whether the buffering effects are specific to certain types of social support. Quarterly data were collected by structured interviews and blood draws. The primary outcome was depression symptom severity, measured by a modified Hopkins Symptom Checklist for Depression. The primary explanatory variables were food insecurity, measured with the Household Food Insecurity Access Scale, and social support, measured with a modified version of the Functional Social Support Questionnaire. We found that food insecurity was associated with depression symptom severity among women but not men, and that social support buffered the impacts of food insecurity on depression. We also found that instrumental support had a greater buffering influence than emotional social support. Interventions aimed at improving food security and strengthening instrumental social support may have synergistic beneficial effects on both mental health and HIV outcomes among PLWHA in resource-limited settings. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Initiat Global Hlth, Cambridge, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.; Muzoora, Conrad] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, MIT, Phillip T & Susan M Ragan Inst, Boston, MA 02114 USA. [Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Hunt, Peter W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Div HIV AIDS, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA 94143 USA. RP Tsai, AC (reprint author), Harvard Ctr Populat & Dev Studies, 9 Bow St, Cambridge, MA 02138 USA. EM atsai@hsph.harvard.edu RI Nguyen, Giang/D-9027-2016; OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI027763, P30 AI27763]; NIMH NIH HHS [K23 MH-79713, K23 MH079713, K23 MH079713-03S1, K23 MH079713-05, K24 MH-087227, K24 MH087227, K24 MH087227-10, MH-79713-03S1, R01 MH-054907, R01 MH054907, R01 MH054907-17] NR 89 TC 74 Z9 74 U1 4 U2 51 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUN PY 2012 VL 74 IS 12 BP 2012 EP 2019 DI 10.1016/j.socscimed.2012.02.033 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 950IR UT WOS:000304643300022 PM 22513248 ER PT J AU Brouwers, HB Biffi, A Ayres, AM Schwab, K Cortellini, L Romero, JM Rost, NS Viswanathan, A Greenberg, SM Rosand, J Goldstein, JN AF Brouwers, H. Bart Biffi, Alessandro Ayres, Alison M. Schwab, Kristin Cortellini, Lynelle Romero, Javier M. Rost, Natalia S. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI Apolipoprotein E Genotype Predicts Hematoma Expansion in Lobar Intracerebral Hemorrhage SO STROKE LA English DT Article DE APOE; cerebral amyloid angiopathy; genetics; hematoma expansion; intracerebral hemorrhage ID CEREBRAL AMYLOID ANGIOPATHY; ANGIOGRAPHY SPOT SIGN; IDENTIFIES PATIENTS; HIGHEST RISK; E EPSILON-2; GROWTH; ASSOCIATION; DIAGNOSIS; MORTALITY; SCORE AB Background and Purpose-Hematoma volume is the most potent predictor of outcome in spontaneous intracerebral hemorrhage (ICH), and hematoma expansion after hospital presentation occurs in up to 40% of individuals. Among patients with lobar ICH, the apolipoprotein E (APOE) epsilon 2 allele predicts larger hematoma volumes at presentation. We investigated whether the epsilon 2 allele also identifies individuals at increased risk of hematoma expansion. Methods-We analyzed 510 patients with primary ICH and genetic data available from an ongoing prospective cohort study. Baseline and follow-up CT scans were assessed for ICH location and volume using computer-assisted volumetric methods. Results-Individuals with lobar ICH who possessed APOE epsilon 2 were at increased risk for hematoma expansion (OR, 2.72; 95% CI, 1.19-6.23; P = 0.009). The highest odds of expansion were in patients who qualified for the diagnosis of cerebral amyloid angiopathy-related ICH and carried the APOE epsilon 2 allele (OR, 6.02; 95% CI, 1.60 -22.58; P = 0.008). There was no effect of epsilon 2 on hematoma expansion in deep ICH and APOE epsilon 4 had no effect on hematoma expansion in lobar or deep ICH. Conclusions-Possession of APOE epsilon 2 predisposes individuals with lobar ICH to hematoma expansion. This effect is even more pronounced in patients with amyloid angiopathy-related ICH, consistent with the epsilon 2 allele's role in vascular amyloid deposition and vessel fragility. (Stroke. 2012; 43: 1490-1495.) C1 [Brouwers, H. Bart] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, Boston, MA 02114 USA. [Brouwers, H. Bart; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Viswanathan, Anand; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Brouwers, H. Bart; Biffi, Alessandro; Ayres, Alison M.; Schwab, Kristin; Cortellini, Lynelle; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Brouwers, H. Bart; Biffi, Alessandro; Ayres, Alison M.; Schwab, Kristin; Cortellini, Lynelle; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Neuroradiol, Boston, MA 02114 USA. [Goldstein, Joshua N.] 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. [Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Brouwers, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM brouwers@chgr.mgh.harvard.edu RI Goldstein, Joshua/H-8953-2016; OI Ayres, Alison/0000-0002-5492-1695 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [R01NS059727, 5K23NS059774, P50NS051343]; Keane Stroke Genetics Research Fund; Edward and Maybeth Sonn Research Fund; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; National Institutes of Health (NIH); American Heart Association; National Institute of Neurological Disorders and Stroke FX All funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the article, or in the decision to submit for publication. The study was funded by National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) grants R01NS059727, 5K23NS059774, the Keane Stroke Genetics Research Fund, and the Edward and Maybeth Sonn Research Fund. Dr Brouwers was supported by the NIH-NINDS Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) fellowship grant P50NS051343. Dr Biffi was supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N).; J.M.R. is on the Imaging Committee of the Desmoteplase in Acute Ischemic Stroke Trial (DIAS) trial and the advisory board of Lundbeck Pharmaceuticals. S. M. G. received a research grant from the National Institutes of Health (NIH); honoraria from Medtronic and Pfizer; and is a consultant/on the advisory board of Hoffman-La Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb Company. J.R. received research grants from the NIH and the American Heart Association. J.N.G. received a research grant from the National Institute of Neurological Disorders and Stroke and is a consultant/on the advisory board of CSL Behring. NR 26 TC 27 Z9 29 U1 0 U2 2 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 2012 VL 43 IS 6 BP 1490 EP + DI 10.1161/STROKEAHA.111.643262 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 948SV UT WOS:000304523800015 PM 22535266 ER PT J AU Allison, SOD Javitt, MC Glanc, P Andreotti, RF Bennett, GL Brown, DL Dubinsky, T Harisinghani, MG Harris, RD Mitchell, DG Pandharipande, PV Pannu, HK Podrasky, AE Shipp, TD Siegel, CL Simpson, L Wong-You-Cheong, JJ Zelop, CM AF Allison, Sandra O. DeJesus Javitt, Marcia C. Glanc, Phyllis Andreotti, Rochelle F. Bennett, Genevieve L. Brown, Douglas L. Dubinsky, Theodore Harisinghani, Mukesh G. Harris, Robert D. Mitchell, Donald G. Pandharipande, Pari V. Pannu, Harpreet K. Podrasky, Ann E. Shipp, Thomas D. Siegel, Cary Lynn Simpson, Lynn Wong-You-Cheong, Jade J. Zelop, Carolyn M. TI ACR Appropriateness Criteria (R) Multiple Gestations SO ULTRASOUND QUARTERLY LA English DT Article DE appropriateness criteria; twin; triplet; multiple gestations ID TWIN TRANSFUSION SYNDROME; BIRTH-WEIGHT DISCORDANCE; FETAL WEIGHT; SONOGRAPHIC PREDICTION; ANTEPARTUM MANAGEMENT; NUCHAL TRANSLUCENCY; GROWTH DISCORDANCE; TRANSVAGINAL ULTRASONOGRAPHY; CHORIONICITY DETERMINATION; 1ST-TRIMESTER ULTRASOUND AB Multiple gestations are high-risk compared with singleton pregnancies. Prematurity and intrauterine growth restrictions are the major sources of morbidity and mortality common to all twin gestations. Monochorionic twins are at a higher risk for twin-twin transfusion, fetal growth restriction, congenital anomalies, vasa previa, velamentous insertion of the umbilical cord and fetal death. Therefore, determination of multiple gestation, amnionicity and chorionicity in the first trimester is important. Follow up examinations to evaluate fetal well-being include assessment of fetal growth and amniotic fluid volume, umbilical artery Doppler, nonstress test and biophysical profile. To date, there is a paucity of literature regarding imaging schedules for follow-up. At the very least, antepartum testing in multiple gestations is recommended in all situations in which surveillance would ordinarily be performed in a singleton pregnancy. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed biennially 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 procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging. C1 [Allison, Sandra O. DeJesus] Georgetown Univ Hosp, Washington, DC 20007 USA. [Javitt, Marcia C.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Andreotti, Rochelle F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Bennett, Genevieve L.] NYU, Med Ctr, New York, NY 10016 USA. [Brown, Douglas L.] 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. [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, Ann E.] Baptist Hosp Miami, S Miami Ctr Women & Infants, Miami, FL USA. [Shipp, Thomas D.] Diagnost Ultrasound Associates, Boston, MA USA. [Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Simpson, Lynn] Columbia Univ, Amer Coll Obstet & Gynecol, New York, NY USA. [Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zelop, Carolyn M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Allison, SOD (reprint author), Amer Coll Radiol, Dept Qual & Safety, 1891 PrestonWhite Dr, Reston, VA 20191 USA. EM sa263@gunet.georgetown.edu NR 81 TC 4 Z9 4 U1 0 U2 2 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 2012 VL 28 IS 2 BP 149 EP 155 DI 10.1097/RUQ.0b013e31824bfc06 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 948WT UT WOS:000304534600014 ER PT J AU Gupta, S Singh, AH Shabbir, A Hahn, PF Harris, G Sahani, D AF Gupta, Supriya Singh, Anand H. Shabbir, Amna Hahn, Peter F. Harris, Gordon Sahani, Dushyant TI Assessing Renal Parenchymal Volume on Unenhanced CT as a Marker for Predicting Renal Function in Patients with Chronic Kidney Disease SO ACADEMIC RADIOLOGY LA English DT Article DE Renal volumetry; split renal function; chronic kidney disease ID GLOMERULAR-FILTRATION-RATE; RELATIVE LUNG-VOLUME; COMPUTED-TOMOGRAPHY; LIVER VOLUME; PULMONARY HYPOPLASIA; PLANNING ORGAN; DONORS; TRANSPLANTATION; ACCURACY; MRI AB Objectives: To estimate renal volume in chronic kidney disease (CKD) patients using a semiautomated software and compare them with split renal function estimates from radionuclide renogram (RR). We proposed that renal volume from unenhanced computed tomography (CT) scans may serve as surrogate marker for assessing renal function in CKD patients. Materials and Methods: Unenhanced multidetector CT scans of 26 patients with CKD (estimated glomerular filtration rate [eGFR] <60 mL/kg/body surface area [BSA]) and 10 controls (eGFR >60 mL/kg/BSA) were analyzed to calculate renal volumes using a semiautomated software (AMIRAV5.2.0). Volumes obtained were then correlated with corresponding eGFR and split renal function estimates from RR. Volumes were also compared with those obtained on enhanced scans in 10 cases (five disease group, five controls). Bland-Altman analysis was used to assess agreement between methods. Results: A moderately positive correlation was found between renal volume obtained on unenhanced CT and eGFR (r = 0.65, P < .0001), whereas a significantly high correlation with split function estimates from RR (r = 0.95, P < .001) was found. Bland-Altman analysis revealed a good agreement between renal volume from CT and renal function from RR (34/36 observations were within 95% CI and there were two outliers). Correlation between volumes obtained from unenhanced and enhanced CT scans was also significant (r = 0.96). Conclusion: In patients with CKD, renal volume derived from unenhanced CT can possibly serve as a surrogate marker for assessing and monitoring renal function reserves to plan further management. C1 [Gupta, Supriya; Hahn, Peter F.; Sahani, Dushyant] Massachusetts Gen Hosp, Dept Abdominal & Intervent Radiol, Boston, MA 02114 USA. [Singh, Anand H.; Harris, Gordon] Massachusetts Gen Hosp, Dept Imaging 3D, Boston, MA 02114 USA. [Singh, Anand H.] Aga Khan Univ, Karachi, Pakistan. RP Gupta, S (reprint author), Massachusetts Gen Hosp, Dept Abdominal & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM riya10.in@gmail.com FU GE Research Foundation FX D.S. received a grant from GE Research Foundation for this project. NR 55 TC 6 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2012 VL 19 IS 6 BP 654 EP 660 DI 10.1016/j.acra.2012.02.006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 946TZ UT WOS:000304381700004 PM 22578224 ER PT J AU Liapakis, IE Paschalis, EI AF Liapakis, Ioannis E. Paschalis, Eleftherios I. TI Liposuction and Suspension of the Orbicularis Oculi for the Correction of Persistent Malar Bags: Description of Technique and Report of a Case SO AESTHETIC PLASTIC SURGERY LA English DT Article DE Malar bags; Orbicularis oculi suspension; Blepharoplasty; Liposuction ID COMPOSITE RHYTIDECTOMY; SUBPERIOSTEAL; REJUVENATION; MIDFACE; LIFT; BLEPHAROPLASTY; DISSECTION; FACELIFT; EYELIDS; MUSCLE AB The purpose of this study was to present an alternative surgical procedure for the correction of persistent malar bags and to review the literature. A 45-year-old female patient with persistent malar bags, secondary to previous blepharoplasty, was admitted. Liposuction of the edema and suspension of the orbicularis muscle to the temporal region was performed through a lateral canthal incision. A successful malar bag removal was demonstrated, exhibiting stable results at the 6-month follow-up. Persistent malar bags resulting from previous blepharoplasty may be difficult to correct with conventional treatment. The combination of liposuction and suspension of the orbicularis oculi is proposed as an efficient alternative for the correction of persistent malar bags. C1 [Liapakis, Ioannis E.] OpsisClin Plast & Reconstruct Surg, Iraklion 71304, Crete, Greece. [Paschalis, Eleftherios I.] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Paschalis, EI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM eleftherios_paschalis@meei.harvard.edu OI Paschalis, Eleftherios/0000-0002-4544-4452 NR 27 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-216X J9 AESTHET PLAST SURG JI Aesthet. Plast. Surg. PD JUN PY 2012 VL 36 IS 3 BP 546 EP 549 DI 10.1007/s00266-011-9838-1 PG 4 WC Surgery SC Surgery GA 944LN UT WOS:000304203800010 PM 22101985 ER PT J AU Lorenzana, SB Hughes, MD Grinsztejn, B Collier, AC Luz, PM Freedberg, KA Wood, R Levison, JH Mugyenyi, PN Salata, R Wallis, CL Weinstein, MC Schooley, RT Walensky, RP AF Lorenzana, Sarah B. Hughes, Michael D. Grinsztejn, Beatriz Collier, Ann C. Luz, Paula Mendes Freedberg, Kenneth A. Wood, Robin Levison, Julie H. Mugyenyi, Peter N. Salata, Robert Wallis, Carole L. Weinstein, Milton C. Schooley, Robert T. Walensky, Rochelle P. TI Genotype assays and third-line ART in resource-limited settings: a simulation and cost-effectiveness analysis of a planned clinical trial SO AIDS LA English DT Article DE A5288; ACTG; antiretroviral therapy; ART; cost-effectiveness; genotype; HIV; resource-limited setting; third-line ART ID ACTIVE ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; VIROLOGICAL FAILURE; DRUG-RESISTANCE; COTE-DIVOIRE; HIV-1-INFECTED PATIENTS; HIV-1 INFECTION; RISK-FACTORS; ADULTS; PREDICTORS AB Objectives: To project the clinical and economic outcomes of a genotype assay for selection of third-line antiretroviral therapy (ART) in resource-limited settings, as per the planned international A5288 trial (MULTI-OCTAVE). Methods: We used the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-International Model to compare three strategies for patients who have failed second-line ART in South Africa: sustained second-line: no genotype assay, all patients remain on second-line ART; A5288: genotype to determine the resistance profile and assign an appropriate regimen; or population-based third-line: no genotype, all patients switch to a potent third-line regimen. Model inputs are from published data in South Africa. Resistance profiles, ART regimens, and efficacy data were those used for trial planning. Results: Projected life expectancy for sustained second-line, A5288, and population-based third-line are 61.1, 103.8, and 104.2 months. Compared to sustained second-line ($ 12 460), per person lifetime costs increase for the A5288 ($ 39 250) and population-based ($ 44 120) strategies. The incremental cost-effectiveness ratio of A5288, compared to sustained second-line, is $ 7500/year of life saved (YLS), and for population-based third-line, compared to A5288, is $ 154 500/YLS. In the A5288 strategy, very late presentation to care, coupled with lengthy delays to obtain the genotype, dramatically reduces 5-year survival, making the population-based third-line strategy more attractive. Conclusions: We project that, whereas the public health approach to third-line therapy is unaffordable, genotype assays and third-line ART in resource-limited settings will increase survival and be cost-effective compared to the population-based approach, supporting the value of an efficacy study. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Freedberg, Kenneth A.; Levison, Julie H.; Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Med, Boston, MA 02114 USA. [Lorenzana, Sarah B.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Div Gen Med, Sch Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA. [Levison, Julie H.; Walensky, Rochelle P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Lorenzana, Sarah B.; Freedberg, Kenneth A.; Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Grinsztejn, Beatriz; Luz, Paula Mendes] Fundacao Oswaldo Cruz, Inst Pesquisas Clin Evandro Chagas, Rio De Janeiro, Brazil. [Collier, Ann C.] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Mugyenyi, Peter N.] Joint Clin Res Ctr, Kampala, Uganda. [Salata, Robert] Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA. [Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. RP Walensky, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org FU National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476, P30 AI060354, AI069434]; AIDS Clinical Trials Group [U01 AI068636, U01 AI068634]; Merck Company; Schering-Plough FX The work was supported by the National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, P30 AI060354, AI069434), and the AIDS Clinical Trials Group (U01 AI068636, U01 AI068634). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; A.C.C. has current or recent past research support from Merck & Company and Schering-Plough. She was a member of a Data, Safety, and Monitoring Board for a Merck-sponsored study. She and an immediate family member own stock in Abbott Laboratories, Bristol Myers Squibb, Johnson and Johnson and Pfizer, Inc.; R.T.S. has served as a consultant to Merck & Company. He serves as a consultant to Johnson and Johnson and to Gilead Sciences. He serves as Chair of a Data, Safety, and Monitoring Board for a Gilead-sponsored study. NR 56 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 1 PY 2012 VL 26 IS 9 BP 1083 EP 1093 DI 10.1097/QAD.0b013e32835221eb PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 946PK UT WOS:000304364900004 PM 22343964 ER PT J AU Ho, JE Scherzer, R Hecht, FM Maka, K Selby, V Martin, JN Ganz, P Deeks, SG Hsue, PY AF Ho, Jennifer E. Scherzer, Rebecca Hecht, Frederick M. Maka, Kristinalisa Selby, Van Martin, Jeffrey N. Ganz, Peter Deeks, Steven G. Hsue, Priscilla Y. TI The association of CD4(+) T-cell counts and cardiovascular risk in treated HIV disease SO AIDS LA English DT Article DE cardiovascular diseases; CD4 cell; HIV; risk factors; vasodilation ID FLOW-MEDIATED DILATION; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; ENDOTHELIAL DYSFUNCTION; BRACHIAL-ARTERY; VIRAL LOAD; INFECTION; ATHEROSCLEROSIS; VASODILATION; INDIVIDUALS AB Objective: HIV-infected individuals are at high risk of developing cardiovascular disease. Whether earlier initiation of HIV therapy at higher CD4(+) cell counts has any effect on cardiovascular risk as assessed by endothelial function is unknown. Design: Cross-sectional study of 74 antiretroviral-treated men with undetectable plasma HIV RNA levels. Methods: Participants underwent noninvasive assessment of endothelial function using brachial artery flow-mediated dilation (FMD). The association of nadir and current CD4(+) T-cell count with FMD was assessed using multivariable linear regression. Results: The median age was 47 years [interquartile range (IQR) 42-55], median current CD4(+) T-cell count was 659 cells/mu l (IQR 542-845), and nadir CD4 cell count was 314 cells/mu l (IQR 150-490). Twenty-eight percent had hypertension, and 32% hyperlipidemia. Nadir CD4(+) T-cell count less than 350 cells/mu l was associated with lower FMD in age-adjusted and race-adjusted analyses and remained an independent predictor of FMD after adjustment for cardiovascular risk factors (hypertension, diabetes, smoking, hyperlipidemia) and HIV-related characteristics (HIV duration, HAART duration). After multivariable adjustment, individuals with nadir CD4(+) T-cell count less than 350 cells/mu l had a 1.22% lower FMD compared with those with higher T-cell counts [95% confidence interval (CI) - 2.20 to 0.19-, P = 0.02]. Proximal CD4(+) T-cell count showed little association with FMD. Conclusion: Among treated HIV-infected individuals, nadir CD4(+) T-cell count less than 350 cells/mu l is independently associated with lower FMD, suggesting that delayed therapy results in sustained harm to endothelial function. Our data support future prospective studies evaluating cardiovascular effects of HAART initiation at higher CD4(+) cell counts. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Maka, Kristinalisa; Selby, Van; Ganz, Peter; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Cardiol, San Francisco, CA 94110 USA. [Ho, Jennifer E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Scherzer, Rebecca] Univ Calif San Francisco, Vet Adm Med Ctr, San Francisco, CA 94110 USA. [Hecht, Frederick M.; Martin, Jeffrey N.; Deeks, Steven G.] Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA 94110 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Cardiol, Room 5G1,1001 Potrero Ave, San Francisco, CA 94110 USA. EM phsue@medsfgh.ucsf.edu OI Ho, Jennifer/0000-0002-7987-4768 FU NIH/University of California, San Francisco-Gladstone Institute of Virology and Immunology Center for AIDS Research [P30-AI027763]; NIH [5R01-HL095130, 5K23-AI066885]; National Institute of Allergy and Infectious Diseases [K24-AI069994]; CFAR Network of Integrated Clinical Systems [R24 AI067039]; UCSF Clinical and Translational Science Institute [UL1 RR024131-01]; Pfizer; Merck; Gilead FX This research was supported by grants from the NIH/University of California, San Francisco-Gladstone Institute of Virology and Immunology Center for AIDS Research, P30-AI027763 (J.E.H); from the NIH, 5R01-HL095130, and 5K23-AI066885 (P.Y.H.); from the National Institute of Allergy and Infectious Diseases, K24-AI069994 (S. G. D.), CFAR Network of Integrated Clinical Systems, R24 AI067039; and the UCSF Clinical and Translational Science Institute, UL1 RR024131-01.; P.Y.H. has received honoraria from Gilead, and grant support from Pfizer. S. G. D. has received grant support from Merck and Gilead and honoraria from GlaxoSmithKline, ViiV, and Tobira. NR 33 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 1 PY 2012 VL 26 IS 9 BP 1115 EP 1120 DI 10.1097/QAD.0b013e328352ce54 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 946PK UT WOS:000304364900007 PM 22382147 ER PT J AU Varraso, R Camargo, CA AF Varraso, Raphaelle Camargo, Carlos A., Jr. TI More evidence for the importance of nutritional factors in chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID DIETARY PATTERNS; RISK-FACTORS; CURED MEATS; VITAMIN-D; US WOMEN; MEN; METAANALYSIS; CONSUMPTION; BURDEN C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Varraso, Raphaelle] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, Villejuif, France. [Varraso, Raphaelle] Univ Paris Sud 11, UMRS 1018, Villejuif, France. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 NR 20 TC 4 Z9 6 U1 1 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2012 VL 95 IS 6 BP 1301 EP 1302 DI 10.3945/ajcn.112.039834 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 946FT UT WOS:000304337600002 PM 22552036 ER PT J AU McCaffery, JM Papandonatos, GD Peter, I Huggins, GS Raynor, HA Delahanty, LM Cheskin, LJ Balasubramanyam, A Wagenknecht, LE Wing, RR AF McCaffery, Jeanne M. Papandonatos, George D. Peter, Inga Huggins, Gordon S. Raynor, Hollie A. Delahanty, Linda M. Cheskin, Lawrence J. Balasubramanyam, Ashok Wagenknecht, Lynne E. Wing, Rena R. CA Genetic Subgrp Look AHEAD Look AHEAD Res Grp TI Obesity susceptibility loci and dietary intake in the Look AHEAD Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GENOME-WIDE ASSOCIATION; NEUROTROPHIC FACTOR BDNF; BODY-MASS INDEX; DIABETES PREVENTION PROGRAM; ENERGY-INTAKE; FTO GENE; EATING FREQUENCY; FOOD-FREQUENCY; ADULT OBESITY; LIFE-STYLE AB Background: Genome-wide association studies (GWAS) have identified consistent associations with obesity. However, the mechanisms remain unclear. Objective: The objective was to determine the association between obesity susceptibility loci and dietary intake. Design: The association of GWAS-identified obesity risk alleles (FTO, MC4R, SH2B1, BDNF, INSIG2, TNNI3K, NISCH-STAB1, MTIF3, MAP2K5, QPCTL/GIPR, and PPARG) with dietary intake, measured through food-frequency questionnaires, was investigated in 2075 participants from the Look AHEAD (Action for Health in Diabetes) clinical trial. We adjusted for age, sex, population stratification, and study site. Results: Obesity risk alleles at FTO rs1421085 significantly predicted more eating episodes per day (P = 0.001) an effect that persisted after adjustment for body weight (P = 0.004). Risk variants within BDNF were significantly associated with more servings from the dairy product and the meat, eggs, nuts, and beans food groups (P <= 0.004). The risk allele at SH2BI rs4788099 was significantly associated with more servings of dairy products (P = 0.001), whereas the risk allele at TNNI3K rs1514176 was significantly associated with a lower percentage of energy from protein (P = 0.002). Conclusion: These findings suggest that obesity risk loci may affect the pattern and content of food consumption among overweight or obese individuals with type 2 diabetes. The Look AHEAD Genetic Ancillary Study was registered at clinicaltrials.gov as NCT01270763 and the Look AHEAD study as NCT00017953. Am J Clin Nutr 2012;95:1477-86. C1 [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Weight Control & Diabet Res Ctr, Miriam Hosp, Providence, RI 02903 USA. [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02903 USA. [Papandonatos, George D.] Brown Univ, Ctr Stat Sci, Providence, RI 02903 USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Huggins, Gordon S.] Tufts Med Ctr, MCRI Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA USA. [Raynor, Hollie A.] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. [Cheskin, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Weight Management Ctr, Dept Hlth Behav & Soc, Baltimore, MD USA. [Balasubramanyam, Ashok] Baylor Coll Med, Diabet & Endocrinol Res Ctr, Translat Metab Unit, Houston, TX 77030 USA. [Wagenknecht, Lynne E.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. RP McCaffery, JM (reprint author), Brown Univ, Weight Control & Diabet Res Ctr, Miriam Hosp, 196 Richmond St, Providence, RI 02903 USA. EM jeanne_mccaffery@brown.edu RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X FU Look AHEAD [U01DK056992-11SI, DK072497]; Department of Health and Human Services through NIH [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt 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 44]; NIH [DK072497, DK 046204]; University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C Banter General Clinical Research Center [M01RR01346] FX Look AHEAD genetic ancillary study funding and support (U01DK056992-11SI and DK072497). Look AHEAD 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 following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases (Barbara Harrison, Van S Hubbard. and Susan Z Yanovski); National Heart, Lung, and Blood Institute (Lawton S Cooper, Jeffrey Cutler, and Eva Obarzanek); National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; and the CDC (Edward W Gregg, David F Williamson, and Ping Zhang). 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 (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 44); NIH grants (DK 046204 and DK072497); the University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and Frederic C Banter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson, Life Scan Inc; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever. NR 66 TC 46 Z9 48 U1 0 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2012 VL 95 IS 6 BP 1477 EP 1486 DI 10.3945/ajcn.111.026955 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 946FT UT WOS:000304337600024 PM 22513296 ER PT J AU Weycker, D Malin, J Barron, R Edelsberg, J Kartashov, A Oster, G AF Weycker, Derek Malin, Jennifer Barron, Rich Edelsberg, John Kartashov, Alex Oster, Gerry TI Comparative Effectiveness of Filgrastim, Pegfilgrastim, and Sargramostim as Prophylaxis Against Hospitalization for Neutropenic Complications in Patients With Cancer Receiving Chemotherapy SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE filgrastim; pegfilgrastim; sargramostim; febrile neutropenia; outcomes ID COLONY-STIMULATING FACTOR; SINGLE-ADMINISTRATION PEGFILGRASTIM; BREAST-CANCER; MYELOSUPPRESSIVE CHEMOTHERAPY; FEBRILE NEUTROPENIA; DOSE-INTENSITY; DOUBLE-BLIND; PHASE-III; RHUGM-CSF; MULTICENTER AB Background: Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim in preventing hospitalization for febrile neutropenia (FN) during myelosuppressive chemotherapy has not been well characterized and is an important clinical question in oncology. Methods: This study used a retrospective cohort design and US healthcare claims data. Source population included patients with solid tumors receiving filgrastim, pegfilgrastim, or sargramostim during their first observed course of chemotherapy between July 2001 and June 2007. For each patient, every unique chemotherapy cycle during the course was identified, along with each cycle in which filgrastim, pegfilgrastim, or sargramostim was administered by the fifth day of the cycle (ie, as prophylaxis). Risks of hospitalization for neutropenic complications (broad definition: admission with a diagnosis of neutropenia, fever, or infection; narrow definition: admission with a diagnosis of neutropenia) and for any reason were examined on a cycle-specific basis during all the cycles in which colony-stimulating factor prophylaxis was administered. Unadjusted and adjusted odds ratios (ORs) for hospitalization were estimated. Results: Risk (unadjusted) of hospitalization for neutropenic complications (narrow definition) was 2.1% for filgrastim prophylaxis (n = 8286), 1.1% for pegfilgrastim prophylaxis (n = 67,247), and 2.5% for sargramostim prophylaxis (n = 1736). Corresponding risks of hospitalization based on the broad definition were 4.0%, 2.6%, and 5.1%. Risks of all-cause hospitalization were 7.9%, 5.3%, and 9.6%, respectively. Adjusted odds of hospitalization were significantly higher for filgrastim [OR (range across the 3 alternative measures of hospitalization): 1.58-1.79; P<0.001] and sargramostim (OR: 1.89-2.68; P<0.001) versus pegfilgrastim. Conclusions: Risk of hospitalization for neutropenic complications during cancer chemotherapy is lower with pegfilgrastim prophylaxis than with filgrastim or sargramostim prophylaxis. C1 [Weycker, Derek; Edelsberg, John; Kartashov, Alex; Oster, Gerry] PAI, Four Davis Court, Brookline, MA 02445 USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Barron, Rich] Amgen Inc, Global Hlth Econ, Thousand Oaks, CA 91320 USA. RP Weycker, D (reprint author), PAI, Four Davis Court, Brookline, MA 02445 USA. EM dweycker@pai2.com FU Amgen Inc FX Funding for this research was provided by Amgen Inc, to Policy Analysis Inc (PAI). NR 28 TC 18 Z9 18 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2012 VL 35 IS 3 BP 267 EP 274 DI 10.1097/COC.0b013e31820dc075 PG 8 WC Oncology SC Oncology GA 946QF UT WOS:000304367400012 PM 21378538 ER PT J AU Alessi, CA Vitiello, MV AF Alessi, Cathy A. Vitiello, Michael V. TI Sleep Disturbance Among Older Adults in Long-Term Care: A Significant Problem in an Important Clinical Setting SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID HOMES C1 [Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Vitiello, Michael V.] Univ Washington, Seattle, WA 98195 USA. RP Alessi, CA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. EM cathy.alessi@va.gov OI Vitiello, Michael/0000-0002-9776-0473 NR 12 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2012 VL 20 IS 6 BP 457 EP 459 DI 10.1097/JGP.0b013e31825688e4 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 945FC UT WOS:000304257200001 PM 22517060 ER PT J AU Martin, JL Jouldjian, S Mitchell, MN Josephson, KR Alessi, CA AF Martin, Jennifer L. Jouldjian, Stella Mitchell, Michael N. Josephson, Karen R. Alessi, Cathy A. TI A Longitudinal Study of Poor Sleep After Inpatient Post-Acute Rehabilitation: The Role of Depression and Pre-Illness Sleep Quality SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Aging; depression; rehabilitation; sleep ID HIP FRACTURE; RATING-SCALE; OLDER-ADULTS; RECOVERY; MORTALITY; SYMPTOMS AB Objectives: To explore the unique impact of poor sleep and symptoms of depression on sleep quality for up to 1 year after inpatient post-acute rehabilitation among older adults. Design: Prospective longitudinal cohort study. Setting: Two inpatient post-acute rehabilitation facilities. Participants: A total of 245 individuals older than 65 years (mean age = 80 years, 38% women). Interventions: None. Measurements: Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) during the post-acute care stay twice to evaluate pre-illness sleep quality and sleep quality during the post-acute care stay, and again at 3-, 6-, 9-, and 12-month follow-up. Demographics, symptoms of depression, cognitive functioning, and comorbidities were also assessed. Results: Across time points, sleep was significantly disturbed for many individuals. Nested regression models predicting PSQI total score at 3, 6, 9, and 12 months showed that variables entered in Block 1 (age, gender, cognitive functioning, and comorbidities) were significant predictors of poor sleep at 6-month follow-up but not at 3-, 9-, or 12-month follow-up. Depression (Block 2) and pre-illness PSQI total score (Block 3) were significant predictors of PSQI total score at all follow-up time points. PSQI total score during post-acute care (Block 4) explained a significant proportion of variance only at the 3-month follow-up. Conclusions: This study confirms that chronic poor sleep is common among older adults during postacute rehabilitation and resolution of sleep disturbance after acute health events may be a lengthy process. Our findings expand understanding of the role of depressive symptoms and preexisting sleep complaints in predicting poor sleep over time among these vulnerable older adults. (Am J Geriatr Psychiatry 2012; 20:477-484) C1 [Martin, Jennifer L.; Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, Jennifer L.; Jouldjian, Stella; Mitchell, Michael N.; Josephson, Karen R.; Alessi, Cathy A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Martin, JL (reprint author), VA GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU NIA [K23 AG028452]; UCLA Claude Pepper Older Americans Independence Center [AG-10415]; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; VA Health Services Research Development [IIR-01-053-1, IIR 04-321-2, AIA-03-047] FX This study was supported by NIA K23 AG028452; UCLA Claude Pepper Older Americans Independence Center (AG-10415), VA Health Services Research & Development IIR-01-053-1, IIR 04-321-2, and AIA-03-047; and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. NR 24 TC 2 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2012 VL 20 IS 6 BP 477 EP 484 DI 10.1097/JGP.0b013e31824877c1 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 945FC UT WOS:000304257200004 PM 22617164 ER PT J AU Fung, CH Martin, JL Chung, C Fiorentino, L Mitchell, M Josephson, KR Jouldjian, S Alessi, C AF Fung, Constance H. Martin, Jennifer L. Chung, Carol Fiorentino, Lavinia Mitchell, Michael Josephson, Karen R. Jouldjian, Stella Alessi, Cathy TI Sleep Disturbance Among Older Adults in Assisted Living Facilities SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Assisted living facilities; long-term care; sleep ID NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; DEPRESSION; QUALITY; SYMPTOMS; INSOMNIA; QUESTIONNAIRE; COMORBIDITY; COMPLAINTS; DIAGNOSIS AB Objectives: To evaluate whether objectively and subjectively measured sleep disturbances persist among older adults in assisted living facilities (ALFs) and to identify predictors of sleep disturbance in this setting. Design: Prospective, observational cohort study. Setting and Participants: A total of 121 residents, age >= 65 years, in 18 ALFs in the Los Angeles area. Measurements: Objective (actigraphy) and subjective (Pittsburgh Sleep Quality Index) sleep measures were collected at baseline and 3- and 6-month follow-up. Predictors of baseline sleep disturbance tested in bivariate analyses and multiple regression models included demographics, Mini-Mental State Examination score, number of comorbidities, nighttime sedating medication use, functional status (activities of daily living; instrumental activities of daily living), restless legs syndrome, and sleep apnea risk. Results: Objective and subjective sleep measures were similar at baseline and 3- and 6-month follow-up (objective nighttime total sleep [hours] 6.3, 6.5, and 6.4; objective nighttime percent sleep 77.2, 77.7, and 78.3; and Pittsburgh Sleep Quality Index total score 8.0, 7.8, and 7.7, respectively). The mean baseline nighttime percent sleep decreased by 2% for each additional unit increase in baseline comorbid conditions (measured as the number of conditions), and increased by 4.5% for each additional unit increase in baseline activities of daily living (measured as the number of activities of daily living), in a multiple regression model. Conclusions: In this study, we found that objectively and subjectively measured sleep disturbances are persistent among ALF residents and are related to a greater number of comorbidities and poorer functional status at baseline. Interventions are needed to improve sleep in this setting. (Am J Geriatr Psychiatry 2012; 20:485-493) C1 [Fung, Constance H.; Martin, Jennifer L.; Josephson, Karen R.; Jouldjian, Stella; Alessi, Cathy] Vet Adm Greater Los Angeles Healthcare Syst, GRECC, North Hills, CA 91343 USA. [Martin, Jennifer L.; Chung, Carol; Mitchell, Michael; Alessi, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fiorentino, Lavinia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Fung, CH (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM Connie.Fung@va.gov FU VA Advanced Geriatrics Fellowship Program; NIH NIA [K23 AG028452]; NIMH [T32 MH 019925-11]; UCLA Academic Senate Council on Research; VA Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center; VA Health Services Research and Development [IIR 04-321-2]; UCLA Cousins Center for Psychoneuroimmunology; Sepracor Inc., Marlborough, MA FX This study was supported by the VA Advanced Geriatrics Fellowship Program; NIH NIA K23 AG028452, NIMH T32 MH 019925-11; UCLA Academic Senate Council on Research; VA Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center; VA Health Services Research and Development (IIR 04-321-2); and UCLA Cousins Center for Psychoneuroimmunology. Additional financial support was provided by Sepracor Inc., Marlborough, MA. The authors thank the study project coordinators, Terry Vandenberg, MA, and Rebecca Saia, the research staff, the staff at the participating facilities, and the ALF residents. NR 39 TC 8 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2012 VL 20 IS 6 BP 485 EP 493 DI 10.1097/JGP.0b013e318252e3e0 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 945FC UT WOS:000304257200005 PM 22531104 ER PT J AU Armand, P Sainvil, MM Kim, HT Rhodes, J Cutler, C Ho, VT Koreth, J Alyea, EP Neufeld, EJ Kwong, RY Soiffer, RJ Antin, JH AF Armand, Philippe Sainvil, Marie-Michele Kim, Haesook T. Rhodes, Joanna Cutler, Corey Ho, Vincent T. Koreth, John Alyea, Edwin P. Neufeld, Ellis J. Kwong, Raymond Y. Soiffer, Robert J. Antin, Joseph H. TI Does iron overload really matter in stem cell transplantation? SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID PRETRANSPLANTATION SERUM FERRITIN; C-REACTIVE PROTEIN; PROGNOSTIC IMPACT; RISK-FACTOR; MYELODYSPLASTIC SYNDROME; PREDICTOR; MALIGNANCIES; RECIPIENTS; MORTALITY; SURVIVAL AB A growing body of evidence suggests that iron overload is associated with inferior outcomes after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). However, all of those studies used surrogate markers of iron overload, especially serum ferritin, and most had a retrospective design. We conducted a prospective observational study in patients with myelodysplastic syndrome or acute leukemia undergoing myeloablative HSCT. Forty-five patients who were followed for over 1 year, with serial measurements of serum iron parameters, as well as liver and cardiac magnetic resonance imaging. There was no significant increase in ferritin, liver or cardiac iron content in the 12 months following HSCT. Although serum ferritin still appeared to have prognostic significance, as previously reported, pre-HSCT iron overload (as reflected in liver iron content) was not associated with increased mortality, relapse, or graft-versus-host disease. These results raise the possibility that the adverse prognostic impact of pre-HSCT hyperferritinemia may be related to factors independent of iron overload. Am. J. Hematol. 87:569572, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Armand, Philippe; Sainvil, Marie-Michele; Cutler, Corey; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Soiffer, Robert J.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02215 USA. [Rhodes, Joanna] SUNY Stony Brook, Dept Med, Sch Med, Stony Brook, NY 11794 USA. [Neufeld, Ellis J.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Cardiovasc Med, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM parmand@partners.org FU Novartis; Novartis Oncology; National Institutes of Health [CA142106-06]; Leukemia and Lymphoma Society; Conquer Cancer/ASCO Foundation; American Society of Hematology FX P.A. and E.N. have received research funding from Novartis.; Contract grant sponsors: Novartis Oncology and the National Institutes of Health; Contract grant number: CA142106-06.; Contract grant sponsors: Leukemia and Lymphoma Society (Special Fellowship in Clinical Research). Contract grant sponsors: Conquer Cancer/ASCO Foundation (Career Development Award).; Contract grant sponsors: American Society of Hematology (Scholar Award). NR 26 TC 32 Z9 32 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2012 VL 87 IS 6 BP 569 EP 572 DI 10.1002/ajh.23188 PG 4 WC Hematology SC Hematology GA 945CC UT WOS:000304249400001 PM 22473510 ER PT J AU Abel, GA Friese, CR Neville, BA Wilson, KM Hastings, BT Earle, CC Keating, NL Richardson, LC AF Abel, Gregory A. Friese, Christopher R. Neville, Bridget A. Wilson, Katherine M. Hastings, B. Taylor Earle, Craig C. Keating, Nancy L. Richardson, Lisa C. TI Referrals for suspected hematologic malignancy: A survey of primary care physicians SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID MULTIPLE-MYELOMA; UNITED-STATES; CANCER; DIAGNOSIS; COMMUNICATION; SYMPTOMS C1 [Abel, Gregory A.; Neville, Bridget A.; Hastings, B. Taylor] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02215 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Leukaemia, Boston, MA 02215 USA. [Friese, Christopher R.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Wilson, Katherine M.; Richardson, Lisa C.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Brigham & Womens Hosp, Div Gen Internal Med, Sch Med, Boston, MA 02115 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave,Dana 1108, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu RI Friese, Christopher/D-2097-2013 OI Friese, Christopher/0000-0002-2281-2056 FU NINR NIH HHS [R00 NR010750] NR 23 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2012 VL 87 IS 6 BP 634 EP 636 DI 10.1002/ajh.23172 PG 3 WC Hematology SC Hematology GA 945CC UT WOS:000304249400014 PM 22473854 ER PT J AU Dolinay, T Kim, YS Howrylak, J Hunninghake, GM An, CH Fredenburgh, L Massaro, AF Rogers, A Gazourian, L Nakahira, K Haspel, JA Landazury, R Eppanapally, S Christie, JD Meyer, NJ Ware, LB Christiani, DC Ryter, SW Baron, RM Choi, AMK AF Dolinay, Tamas Kim, Young Sam Howrylak, Judie Hunninghake, Gary M. An, Chang Hyeok Fredenburgh, Laura Massaro, Anthony F. Rogers, Angela Gazourian, Lee Nakahira, Kiichi Haspel, Jeffrey A. Landazury, Roberto Eppanapally, Sabitha Christie, Jason D. Meyer, Nuala J. Ware, Lorraine B. Christiani, David C. Ryter, Stefan W. Baron, Rebecca M. Choi, Augustine M. K. TI Inflammasome-regulated Cytokines Are Critical Mediators of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; inflammasome; interleukin-18; mechanical ventilation ID RESPIRATORY-DISTRESS-SYNDROME; INTENSIVE-CARE-UNIT; NALP3 INFLAMMASOME; IMMUNE-RESPONSES; IL-18 SECRETION; SEPSIS; ACTIVATION; CASPASE-1; MORTALITY; MICE AB Rationale: Despite advances in clinical management, there are currently no reliable diagnostic and therapeutic targets for acute respiratory distress syndrome (ARDS). The inflammasome/caspase-1 pathway regulates the maturation and secretion of proinflammatory cytokines (e.g., IL-18). IL-18 is associated with injury in animal models of systemic inflammation. Objectives: We sought to determine the contribution of the inflammasome pathway in experimental acute lung injury and human ARDS. Methods: We performed comprehensive gene expression profiling on peripheral blood from patients with critical illness. Gene expression changes were assessed using real-time polymerase chain reaction, and IL-18 levels were measured in the plasma of the critically ill patients. Wild-type mice or mice genetically deficient in IL-18 or caspase-1 were mechanically ventilated using moderate tidal volume (12 ml/kg). Lung injury parameters were assessed in lung tissue, serum, and bronchoalveolar lavage fluid. Measurements and Main Results: In mice, mechanical ventilation enhanced IL-18 levels in the lung, serum, and bronchoalveolar lavage fluid. IL-18 neutralizing antibody treatment, or genetic deletion of IL-18 or caspase-1, reduced lung injury in response to mechanical ventilation. In human patients with ARDS, inflammasome-related mRNA transcripts (CASP1, IL1B, and IL18) were increased in peripheral blood. In samples from four clinical centers, IL-18 was elevated in the plasma of patients with ARDS (sepsis or trauma-induced ARDS) and served as a novel biomarker of intensive care unit morbidity and mortality. Conclusions: The inflammasome pathway and its downstream cytokines play critical roles in ARDS development. C1 [Choi, Augustine M. K.] Harvard Univ, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Med Sch,Dept Med, Boston, MA 02115 USA. [Eppanapally, Sabitha] Brigham & Womens Hosp, Dept Med, Div Renal Med, Boston, MA 02115 USA. [Howrylak, Judie; Hunninghake, Gary M.; Rogers, Angela] Channing Labs, Boston, MA USA. [Christie, Jason D.; Meyer, Nuala J.] Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Ware, Lorraine B.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. [Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Choi, AMK (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Med Sch,Dept Med, 75 Francis St, Boston, MA 02115 USA. EM amchoi@rics.bwh.harvard.edu FU National Institutes of Health [PO-HL108801, R01-HL079904]; FAMRI; [R01-HL081619]; [P01-HL079063] FX Supported by National Institutes of Health grants PO-HL108801, R01-HL079904, and an FAMRI clinical innovator award (A.M.K.C.); and R01-HL081619 and P01-HL079063 (J.D.C.). NR 50 TC 126 Z9 136 U1 2 U2 20 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 1 PY 2012 VL 185 IS 11 BP 1225 EP 1234 DI 10.1164/rccm.201201-0003OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 946VC UT WOS:000304384600016 PM 22461369 ER PT J AU Verma, S Turkbey, B Muradyan, N Rajesh, A Cornud, F Haider, MA Choyke, PL Harisinghani, M AF Verma, Sadhna Turkbey, Baris Muradyan, Naira Rajesh, Arumugam Cornud, Francois Haider, Masoom A. Choyke, Peter L. Harisinghani, Mukesh TI Overview of Dynamic Contrast-Enhanced MRI in Prostate Cancer Diagnosis and Management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE diffusion-weighted imaging; MR spectroscopy; prostate cancer; prostate MRI; tumor angiogenesis ID EXTERNAL-BEAM RADIOTHERAPY; RADICAL PROSTATECTOMY; PHARMACOKINETIC PARAMETERS; LOCAL RECURRENCE; PERIPHERAL ZONE; DCE-MRI; LOCALIZATION; DIFFUSION; TUMOR; GLAND AB OBJECTIVE. This article is a primer on the technical aspects of performing a high-quality dynamic contrast-enhanced MRI (DCE-MRI) examination of the prostate gland. CONCLUSION. DCE-MRI is emerging as a useful clinical technique as part of a multiparametric approach for evaluating the extent of primary and recurrent prostate cancer. Performing a high-quality DCE-MRI examination requires a good understanding of the technical aspects and limitations of image acquisition and postprocessing techniques. C1 [Verma, Sadhna] Univ Cincinnati, Med Ctr, Dept Radiol, Cincinnati, OH 45267 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Muradyan, Naira] iCAD Inc, Nashua, NH USA. [Rajesh, Arumugam] Univ Hosp Leicester NHS Trust, Leicester Gen Hosp, Leicester, Leics, England. [Cornud, Francois] Hop Cochin, F-75674 Paris, France. [Haider, Masoom A.] Univ Toronto, Dept Radiol, Toronto, ON M5S 1A1, Canada. [Haider, Masoom A.] Univ Hlth Network, Toronto, ON, Canada. [Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Verma, S (reprint author), Univ Cincinnati, Med Ctr, Dept Radiol, 234 Goodman St,POB 670761, Cincinnati, OH 45267 USA. EM drsadhnaverma@gmail.com NR 67 TC 81 Z9 88 U1 1 U2 11 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 2012 VL 198 IS 6 BP 1277 EP 1288 DI 10.2214/AJR.12.8510 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 946ZX UT WOS:000304397500030 PM 22623539 ER PT J AU Bai, XY Wu, CL AF Bai, Xiaoyan Wu, Chin-Lee TI Renal Cell Carcinoma and Mimics: Pathologic Primer for Radiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chromophobe renal cell carcinoma (RCC); clear cell RCC; papillary RCC; primer; renal oncocytoma ID TUBULOCYSTIC CARCINOMA; MOLECULAR CHARACTERIZATION; TRANSLOCATION CARCINOMAS; KIDNEY; SPINDLE; NEUROBLASTOMA; EXPRESSION; NEOPLASIA; DISTINCT; DISEASE AB OBJECTIVE. The purpose of this article is to present a primer to review the gross and microscopic characteristics of the common types of renal cell carcinoma (RCC), such as clear cell RCC, papillary RCC, and chromophobe RCC. Renal oncocytoma and several new and emerging types of RCC are also described, such as tubulocystic carcinoma, acquired cystic kidney disease-associated RCC, clear cell papillary RCC, and oncocytic papillary RCC. CONCLUSION. This primer provides a concise description of the pathologic characteristics fo RCC for radiologists C1 [Bai, Xiaoyan] So Med Univ, Nanfang Hosp, Div Nephrol, Guangzhou, Guangdong, Peoples R China. [Bai, Xiaoyan] Guangdong Prov Inst Nephrol, Guangzhou, Guangdong, Peoples R China. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Wu, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM cwu2@partners.org NR 24 TC 1 Z9 3 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2012 VL 198 IS 6 BP 1289 EP 1293 DI 10.2214/AJR.12.8586 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 946ZX UT WOS:000304397500031 PM 22623540 ER PT J AU Lichtenberger, JP Sharma, A Zachary, KC Krishnam, MS Greene, RE Shepard, JAO Wu, CC AF Lichtenberger, John P., III Sharma, Amita Zachary, Kimon C. Krishnam, Mayil S. Greene, Reginald E. Shepard, Jo-Anne O. Wu, Carol C. TI What a Differential a Virus Makes: A Practical Approach to Thoracic Imaging Findings in the Context of HIV Infection-Part 1, Pulmonary Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE differential diagnosis; HIV; pulmonary; thoracic ID LYMPHOCYTIC INTERSTITIAL PNEUMONIA; MULTICENTRIC CASTLEMAN-DISEASE; PNEUMOCYSTIS-CARINII PNEUMONIA; HUMAN-IMMUNODEFICIENCY-VIRUS; CT FINDINGS; KAPOSIS-SARCOMA; PATHOLOGICAL FINDINGS; UNITED-STATES; LYMPHOPROLIFERATIVE DISORDERS; BACILLARY ANGIOMATOSIS AB OBJECTIVE. The Centers for Disease Control and Prevention reported more than one million people with HIV infection in the United States in 2006, an increase of 11% over 3 years. Worldwide, nearly 34 million people are infected with HIV. Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-infected patients, underscoring the importance of understanding the pulmonary manifestations in this population. When presented with a chest radiograph or CT image of a patient with the clinical history of HIV infection, one approach is to start by identifying and categorizing key imaging findings. In some instances, the key findings may be further subcategorized to narrow the differential diagnosis, such as distinguishing between perilymphatic distribution and the random distribution of micronodules. The differential diagnosis of these key imaging findings can also be further refined by incorporating clinical data, such as patient demographics, CD4 count, and presenting symptoms. Finally, the change of thoracic disease and clinical status in response to treatment provides important diagnostic information. The purpose of this article is to discuss pulmonary findings in patients with HIV. CONCLUSION. By developing a systematic and practical approach to key pulmonary imaging findings in HIV-infected patients, radiologists can generate clinically relevant and succinct differential diagnoses and thereby improve patient care. C1 [Lichtenberger, John P., III; Sharma, Amita; Greene, Reginald E.; Shepard, Jo-Anne O.; Wu, Carol C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. [Zachary, Kimon C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Div Infect Dis, Boston, MA 02114 USA. [Krishnam, Mayil S.] Univ Calif Irvine, Med Ctr, Dept Radiol Sci, Div Diagnost Cardiovasc & Thorac Imaging, Orange, CA USA. RP Lichtenberger, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Imaging & Intervent,Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM john.lichtenberger@gmail.com NR 52 TC 5 Z9 5 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2012 VL 198 IS 6 BP 1295 EP 1304 DI 10.2214/AJR.11.8003 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 946ZX UT WOS:000304397500032 PM 22623541 ER PT J AU Lichtenberger, JP Sharma, A Zachary, KC Krishnam, MS Greene, RE Shepard, JAO Wu, CC AF Lichtenberger, John P., III Sharma, Amita Zachary, Kimon C. Krishnam, Mayil S. Greene, Reginald E. Shepard, Jo-Anne O. Wu, Carol C. TI What a Differential a Virus Makes: A Practical Approach to Thoracic Imaging Findings in the Context of HIV Infection-Part 2, Extrapulmonary Findings, Chronic Lung Disease, and Immune Reconstitution Syndrome SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE differential diagnosis; HIV; pulmonary; thoracic ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PULMONARY ARTERIAL-HYPERTENSION; MULTICENTRIC CASTLEMAN-DISEASE; ANTIRETROVIRAL THERAPY; INFLAMMATORY SYNDROME; CT FINDINGS; BACILLARY ANGIOMATOSIS; PERICARDIAL-EFFUSION; KAPOSI-SARCOMA; AIDS AB OBJECTIVE. The Centers for Disease Control and Prevention reported more than one million people with HIV infection in the United States in 2006, an increase of 11% over 3 years. Worldwide, nearly 34 million people are infected with HIV. Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-seropositive patients, underscoring the importance of understanding the range of cardiothoracic imaging findings associated with HIV infection. This article will cover extrapulmonary thoracic diseases, chronic lung diseases, and immune reconstitution inflammatory syndrome in HIV-infected patients. Our approach is focused on the radiologist's perspective by recognizing and categorizing key imaging findings to generate a differential diagnosis. The differential diagnosis can be further refined by incorporating clinical data, such as patient demographics, CD4 count, and presenting symptoms. In addition, with prolonged survival of HIV-infected patients in the era of highly active antiretroviral therapy, radiologists can also benefit from awareness of imaging features of a myriad of chronic cardiopulmonary diseases in this patient population. Finally, the change of imaging findings and clinical status in response to treatment provides important diagnostic information, such as in immune reconstitution syndrome. CONCLUSION. Developing a practical approach to key cardiothoracic imaging findings in HIV-infected patients will aid the radiologist in generating a clinically relevant differential diagnosis and interpretation, thereby improving patient care. C1 [Lichtenberger, John P., III; Sharma, Amita; Greene, Reginald E.; Shepard, Jo-Anne O.; Wu, Carol C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Thorac Imaging & Intervent, Boston, MA 02114 USA. [Zachary, Kimon C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Div Infect Dis, Boston, MA 02114 USA. [Krishnam, Mayil S.] Univ Calif Irvine, Med Ctr, Div Diagnost Cardiovasc & Thorac Imaging, Dept Radiol Sci, Orange, CA USA. RP Lichtenberger, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Thorac Imaging & Intervent, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM john.lichtenberger@gmail.com NR 48 TC 5 Z9 5 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2012 VL 198 IS 6 BP 1305 EP 1312 DI 10.2214/AJR.11.8004 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 946ZX UT WOS:000304397500033 PM 22623542 ER PT J AU Guitchounts, G Stewart, DS Forman, SA AF Guitchounts, Grigori Stewart, Deirdre S. Forman, Stuart A. TI Two Etomidate Sites in alpha 1 beta 2 gamma 2 gamma-Aminobutyric Acid Type A Receptors Contribute Equally and Noncooperatively to Modulation of Channel Gating SO ANESTHESIOLOGY LA English DT Article ID ANESTHETIC BINDING-SITE; GABA(A) RECEPTOR; POTENTIATION; ARRANGEMENT; ACTIVATION; MECHANISMS; MUTATIONS; SUBUNITS AB Background: Etomidate is a potent hypnotic agent that acts via gamma-aminobutyric acid receptor type A (GABA(A)) receptors. Evidence supports the presence of two etomidate sites per GABA(A) receptor, and current models assume that each site contributes equally and noncooperatively to drug effects. These assumptions remain untested. Methods: We used concatenated dimer (beta 2-alpha 1) and trimer (gamma 2-beta 2-alpha 1) GABA(A) subunit assemblies that form functional alpha 1 beta 2 gamma 2 channels, and inserted alpha 1M236W etomidate site mutations into both dimers (beta 2-alpha 1M236W) and trimers (gamma 2-beta 2-alpha 1M236W). Wild-type or mutant dimers (D-wt or D-alpha M236W) and trimers (T-wt or T-alpha M236W) were coexpressed in Xenopus oocytes to produce four types of channels: (DTwt)-T-wt, (DTwt)-T-alpha M236W, (DT alpha M236W)-T-wt, and (DT alpha M236W)-T-alpha M236W. For each channel type, two-electrode voltage clamp was performed to quantitatively assess GABA EC50, etomidate modulation (left shift), etomidate direct activation, and other functional parameters affected by alpha M236W mutations. Results: Concatenated wild-type (DTwt)-T-wt channels displayed etomidate modulation and direct activation similar to alpha 1 beta 2 gamma 2 receptors formed with free subunits. (DT alpha M236W)-T-alpha M236W receptors also displayed altered GABA sensitivity and etomidate modulation similar to mutated channels formed with free subunits. Both single-site mutant receptors ((DTwt)-T-alpha M236W and (DT alpha M236W)-T-wt) displayed indistinguishable functional properties and equal gating energy changes for GABA activation (-4.9 +/- 0.48 vs. -4.7 +/- 0.48 kJ/mol, respectively) and etomidate modulation (-3.4 +/- 0.49 vs. -3.7 +/- 0.38 kJ/mol, respectively), which together accounted for the differences between (DTwt)-T-wt and (DT alpha M236W)-T-alpha M236W channels. Conclusions: These results support the hypothesis that the two etomidate sites on alpha 1 beta 2 gamma 2 GABA(A) receptors contribute equally and noncooperatively to drug interactions and gating effects. C1 [Stewart, Deirdre S.; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Guitchounts, Grigori] Boston Univ, Dept Neurobiol, Boston, MA 02215 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, Bethesda, Maryland [R01GM089745, P01GM58448]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication November 11, 2011. Accepted for publication February 16, 2012. Supported by grant nos. R01GM089745 and P01GM58448 from National Institutes of Health, Bethesda, Maryland (to Dr. Forman), and a research award from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital (to Guitchounts). Presented in part at the annual meeting of American Society of Anesthesiologists, October 16, 2011, Chicago, Illinois, and the annual meeting of Society for Neuroscience, November 14, 2011, Washington, D.C. NR 25 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2012 VL 116 IS 6 BP 1235 EP 1244 DI 10.1097/ALN.0b013e3182567df3 PG 10 WC Anesthesiology SC Anesthesiology GA 946MR UT WOS:000304356500014 PM 22531336 ER PT J AU Cusack, JC Hughes, KS AF Cusack, James C., Jr. Hughes, Kevin S. TI Managing Patients at High Risk for Hereditary Breast Cancer: A Guide for the Practicing Physician SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID STATEMENT; SOCIETY C1 [Cusack, James C., Jr.; Hughes, Kevin S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Cusack, JC (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jcusack@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2012 VL 19 IS 6 BP 1721 EP 1722 DI 10.1245/s10434-012-2255-0 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 944NF UT WOS:000304209800001 PM 22411203 ER PT J AU Drohan, B Roche, CA Cusack, JC Hughes, KS AF Drohan, Brian Roche, Constance A. Cusack, James C., Jr. Hughes, Kevin S. TI Hereditary Breast and Ovarian Cancer and Other Hereditary Syndromes: Using Technology to Identify Carriers SO ANNALS OF SURGICAL ONCOLOGY LA English DT Review ID BRCA2; SUSCEPTIBILITY; BREAST/OVARIAN; PROBABILITIES; PENETRANCE; PREDICTION; MUTATIONS; GENES; WOMEN; MODEL AB Most patients who harbor a genetic mutation for hereditary breast cancer have not been identified, despite the availability of genetic testing. Developing an effective approach to the identification of high-risk individuals is the key to preventing and/or providing early diagnosis of cancer in this patient population. This educational review addresses these issues. Using data available on the internet, and making assumptions regarding the types and results of genetic testing, we have estimated the number of mutation carriers in the country and the number who have been tested and identified as such. Overall, our ability to fund and more effectively manage carriers is weak. A technological solution is discussed. C1 [Drohan, Brian; Roche, Constance A.; Cusack, James C., Jr.; Hughes, Kevin S.] Harvard Univ, Sch Med, Dept Surg,Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr,Div Surg Oncol, Boston, MA 02115 USA. [Hughes, Kevin S.] Harvard Univ, Bermuda Canc Genet & Risk Assessment Clin, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Drohan, B (reprint author), Harvard Univ, Sch Med, Dept Surg,Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr,Div Surg Oncol, Boston, MA 02115 USA. EM jcusack@partners.org; kshughes@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU Myriad Genetics FX This educational review is part of a series, "Risk Assessment and Genetic Testing for Hereditary Breast Cancer," which has been supported by an educational grant from Myriad Genetics. NR 21 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2012 VL 19 IS 6 BP 1732 EP 1737 DI 10.1245/s10434-012-2257-y PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 944NF UT WOS:000304209800003 PM 22427173 ER PT J AU Pedroso, FE Raut, CP Xiao, H Yeo, CJ Koniaris, LG AF Pedroso, Felipe E. Raut, Chandrajit P. Xiao, Hong Yeo, Charles J. Koniaris, Leonidas G. TI Has the Survival Rate for Surgically Resected Gastric Gastrointestinal Stromal Tumors Improved in the Tyrosine Kinase Inhibitor Era? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID TERM-FOLLOW-UP; IMATINIB MESYLATE; PROGNOSTIC-FACTORS; DOSE IMATINIB; MANAGEMENT; TRIAL; LEIOMYOSARCOMAS; STOMACH; RECURRENCE; DIAGNOSIS AB Tyrosine kinase inhibitor (TKI) therapy for patients with gastrointestinal stromal tumors (GISTs) has been shown to improve overall outcomes. It remains unclear whether TKIs are delaying tumor recurrence or actually affecting cure rates. We sought to determine whether changes in overall and disease-specific survival (OS and DSS, respectively) for patients with surgically resected gastric GISTs have been observed after the introduction of TKI therapies by using population-based data. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with resected gastric mesenchymal tumors before the introduction of TKIs (pre-TKI: 1990-1994) and after their inception (post-TKI: 2002-2003). Overall, 594 patients with gastric mesenchymal tumors were identified, and 189 and 405 underwent resection in the pre- and post-TKI eras, respectively. Between groups, there were no significant differences in patient demographics. The 1- and 6-year OS improved from 84 and 36 to 93 and 71%, respectively. The 1- and 6-year DSS improved from 92 and 62 to 96 and 90%, respectively. Through 6 years, OS and DSS significantly improved for all stages, tumor sizes, and extent of operation. By using multivariate analysis, undergoing treatment in the pre-TKI era was an independent negative predictor of OS, hazard ratio (HR, 2.98) and DSS (HR, 3.81). The TKI era is associated with dramatic improvements in OS and DSS for patients with surgically resected gastric GISTs, irrespective of stage, tumor size, and extent of operation through 6 years of follow-up. It remains unclear, however, whether this survival advantage is a change in cure rate or simply a delay in disease progression. C1 [Pedroso, Felipe E.; Yeo, Charles J.; Koniaris, Leonidas G.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. [Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Dept Surg,Ctr Sarcoma & Bone Oncol,Div Surg Oncol, Boston, MA 02115 USA. [Xiao, Hong] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Econ Social & Adm Pharm, Tallahassee, FL 32307 USA. RP Pedroso, FE (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. EM leonidas.koniaris@jefferson.edu FU NIH Supplement to Promote Diversity in Health-Related Research [R01 GM092758-01A1S1] FX This work was partially supported by the following NIH Supplement to Promote Diversity in Health-Related Research R01 GM092758-01A1S1 (F.E.P.). NR 35 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2012 VL 19 IS 6 BP 1748 EP 1758 DI 10.1245/s10434-012-2222-9 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 944NF UT WOS:000304209800006 PM 22290567 ER PT J AU Seki, H Hayashida, T Jinno, H Hirose, S Sakata, M Takahashi, M Maheswaran, S Mukai, M Kitagawa, Y AF Seki, Hirohito Hayashida, Tetsu Jinno, Hiromitsu Hirose, Shigemichi Sakata, Michio Takahashi, Maiko Maheswaran, Shyamala Mukai, Makio Kitagawa, Yuko TI HOXB9 Expression Promoting Tumor Cell Proliferation and Angiogenesis Is Associated with Clinical Outcomes in Breast Cancer Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; MICROVESSEL DENSITY; KI-67 ANTIGEN; METASTASIS; CARCINOMA; SURVIVAL; GROWTH; BASAL; SECTIONS; THERAPY AB Studies have suggested that HOXB9 expression in breast cancer cells promotes cellular invasiveness, metastatic ability, and tumor neovascularization in the surrounding tissue in and assays. These findings imply that HOXB9 overexpression may alter tumor-specific cell fates and the tumor stromal microenvironment, contributing to breast cancer progression. The objective of this study was to analyze whether these results could be applied to clinical practice. A total of 141 consecutive, invasive ductal carcinoma patients who underwent surgical treatment were examined. Immunohistochemical staining was performed to evaluate the expression of HOXB9, Ki-67, CD31, and CD34, and the association of tumor proliferation and angiogenesis with HOXB9 expression was analyzed. Of the 141 tumor specimens immunostained for HOXB9, 69 (48.9%) stained positive. Larger primary tumor size, hormone receptor negativity, HER2 positivity, higher nuclear grade, and number of pathologic nodal metastases were significant variables associated with HOXB9 expression. Notably, 12 (92.3%) of 13 triple-negative breast cancer cases showed HOXB9 expression. Disease-free survival and overall survival were significantly different between the HOXB9-positive and HOXB9-negative groups (hazard ratio 20.714, = 0.001; and hazard ratio 9.206, = 0.003, respectively). Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for disease-free survival (hazard ratio 15.532, = 0.009). HOXB9-positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio compared with HOXB9-negative tumors. HOXB9 expression, which promotes tumor proliferation and angiogenesis, is a significant prognostic factor in breast cancer. C1 [Seki, Hirohito; Hayashida, Tetsu; Jinno, Hiromitsu; Sakata, Michio; Takahashi, Maiko; Kitagawa, Yuko] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan. [Hirose, Shigemichi; Mukai, Makio] Keio Univ, Sch Med, Div Diagnost Pathol, Tokyo 160, Japan. [Maheswaran, Shyamala] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA USA. [Maheswaran, Shyamala] Harvard Univ, Sch Med, Charlestown, MA USA. RP Seki, H (reprint author), Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan. EM tetsu@z7.keio.jp FU Ministry of Education, Culture, Sports, Science and Technology [21791260, 23791499, 22591442, 21591677]; Keio University FX The authors thank Chisato Saito, Hiroshi Okazaki, and Kazuhiro Miyao for their technical support and helpful discussions. This research was supported by the Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research [B] (21791260 and 23791499 to T.H.) and [C] (22591442 to H.J., 21591677 to M.T.), and a Grant-in-Aid from the Global Center of Excellence Program entitled "Education and Research Center for Stem Cell Medicine" (Keio University). NR 36 TC 18 Z9 19 U1 1 U2 5 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 2012 VL 19 IS 6 BP 1831 EP 1840 DI 10.1245/s10434-012-2295-5 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 944NF UT WOS:000304209800016 PM 22396001 ER PT J AU Morikawa, T Kuchiba, A Qian, ZR Mino-Kenudson, M Hornick, JL Yamauchi, M Imamura, Y Liao, XY Nishihara, R Meyerhardt, JA Fuchs, CS Ogino, S AF Morikawa, Teppei Kuchiba, Aya Qian, Zhi Rong Mino-Kenudson, Mari Hornick, Jason L. Yamauchi, Mai Imamura, Yu Liao, Xiaoyun Nishihara, Reiko Meyerhardt, Jeffrey A. Fuchs, Charles S. Ogino, Shuji TI Prognostic Significance and Molecular Associations of Tumor Growth Pattern in Colorectal Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; BRAF V600E MUTATION; MICROSATELLITE-INSTABILITY; COLON-CANCER; RECTAL-CANCER; LINE-1 HYPOMETHYLATION; MULTIVARIATE-ANALYSIS; MISMATCH REPAIR; POOR SURVIVAL AB Infiltrative growth pattern at the tumor margin has been associated with shorter patient survival. However, little is known about the prognostic significance of tumor growth pattern, independent of tumoral molecular alterations and other histologic features. Utilizing a database of 1139 colon and rectal cancer patients in two prospective cohort studies, histologic features including tumor growth pattern, tumor differentiation, lymphocytic reaction, mucinous component, and signet ring cell component were recorded by a single pathologist. Cox proportional hazard model was used to compute mortality hazard ratio, adjusting for clinical, pathologic, and tumor molecular features, including microsatellite instability, the CpG island methylator phenotype, long interspersed nucleotide element 1 (LINE-1) methylation, and and mutations. Among 1139 colorectal cancers, we observed expansile growth pattern in 372 tumors (33%), intermediate growth pattern in 610 tumors (54%), and infiltrative growth pattern in 157 tumors (14%). Compared to patients with expansile growth pattern, those with infiltrative growth pattern experienced shorter cancer-specific survival (log rank < 0.0001; multivariate hazard ratio 1.74; 95% confidence interval 1.22-2.47) and overall survival (log rank < 0.0001; multivariate hazard ratio 1.78; 95% confidence interval 1.33-2.39). The prognostic association of infiltrative growth pattern was confined to patients with stage I-III disease ( (interaction) with stage = 0.0001). Infiltrative growth pattern was associated with worse prognosis among stage I-III colorectal cancer patients, independent of other clinical, pathologic, and molecular characteristics. C1 [Morikawa, Teppei; Kuchiba, Aya; Qian, Zhi Rong; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Morikawa, Teppei; Kuchiba, Aya; Qian, Zhi Rong; Mino-Kenudson, Mari; Hornick, Jason L.; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hornick, Jason L.; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Morikawa, T (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM tmorikawa-tky@umin.ac.jp OI Qian, Zhi rong/0000-0003-1633-4120 FU U.S. National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA151993]; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science FX We thank the participants and staff of the Nurses' Health Study and the Health Professionals Follow-up Study, for their valuable contributions as well as 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 U.S. National Institute of Health (NIH) grants P01 CA87969 (to S. Hankinson), P01 CA55075 (to W. Willett), P50 CA127003 (to C.S.F.), and R01 CA151993 (to S.O.) and by grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. T.M. was supported by a fellowship grant from the Japan Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 37 Z9 37 U1 0 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 2012 VL 19 IS 6 BP 1944 EP 1953 DI 10.1245/s10434-011-2174-5 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 944NF UT WOS:000304209800031 PM 22189472 ER PT J AU Lindquist, KA Wager, TD Kober, H Bliss-Moreau, E Barrett, LF AF Lindquist, Kristen A. Wager, Tor D. Kober, Hedy Bliss-Moreau, Eliza Barrett, Lisa Feldman TI The brain basis of emotion: A meta-analytic review SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article DE Discrete emotion; emotion experience; emotion perception; meta-analysis; neuroimaging; psychological construction ID MEDIAL PREFRONTAL CORTEX; MIDBRAIN PERIAQUEDUCTAL GRAY; BILATERAL AMYGDALA DAMAGE; SKIN-CONDUCTANCE RESPONSE; ANTERIOR CINGULATE CORTEX; VOXEL-BASED METAANALYSIS; TEMPORAL-LOBE EPILEPSY; MONKEYS MACACA-MULATTA; ORBITOFRONTAL CORTEX; FACIAL EXPRESSIONS AB Researchers have wondered how the brain creates emotions since the early days of psychological science. With a surge of studies in affective neuroscience in recent decades, scientists are poised to answer this question. In this target article, we present a meta-analytic summary of the neuroimaging literature on human emotion. We compare the locationist approach (i.e., the hypothesis that discrete emotion categories consistently and specifically correspond to distinct brain regions) with the psychological constructionist approach (i.e., the hypothesis that discrete emotion categories are constructed of more general brain networks not specific to those categories) to better understand the brain basis of emotion. We review both locationist and psychological constructionist hypotheses of brain-emotion correspondence and report meta-analytic findings bearing on these hypotheses. Overall, we found little evidence that discrete emotion categories can be consistently and specifically localized to distinct brain regions. Instead, we found evidence that is consistent with a psychological constructionist approach to the mind: A set of interacting brain regions commonly involved in basic psychological operations of both an emotional and non-emotional nature are active during emotion experience and perception across a range of discrete emotion categories. C1 [Lindquist, Kristen A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA 02129 USA. [Lindquist, Kristen A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Wager, Tor D.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Kober, Hedy] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Bliss-Moreau, Eliza] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Bliss-Moreau, Eliza] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA 02129 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA 02129 USA. RP Lindquist, KA (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA 02129 USA. EM lindqukr@nmr.mgh.harvard.edu; tor.wager@colorado.edu; hedy.kober@yale.edu; eblissmoreau@ucdavis.edu; l.barrett@neu.edu FU National Science Foundation (NSF) [NSF 0631637]; Harvard University Mind/Brain/Behavior Initiative; National Institute of Mental Health (NIMH) [R01MH076136]; National Institutes of Health (NIH) [DP1OD003312]; National Institute on Aging (NIA) [R01 AG030311]; Army Reasearch Institute (ARI) [W91WAW-08-C-0018] FX We thank Amitai Shenhav for his insights into the amygdala's the role in uncertainty, Natasha Sarkisian for her advice on logistic regression, and Kurt Gray for his help with Figure 5. We also thank James Russell, Elizabeth Kensinger, Hiram Brownell, Jerry Clore, and Stephan Hamann who commented on an earlier draft of this manuscript. This project was supported by a National Science Foundation (NSF) Graduate Research Fellowship and a Harvard University Mind/Brain/Behavior Initiative Postdoctoral Fellowship to Kristen Lindquist; a NSF Graduate Research Fellowship to Hedy Kober; a NSF grant (NSF 0631637) and a National Institute of Mental Health (NIMH) grant (R01MH076136) to Tor Wager; and a National Institutes of Health (NIH) Director's Pioneer Award (DP1OD003312), an National Institute on Aging (NIA) grant (R01 AG030311), and an Army Reasearch Institute (ARI) contract (W91WAW-08-C-0018) to Lisa Feldman Barrett. The views, opinions, and/or findings contained in this article are solely those of the authors and should not be construed as an official Department of the Army or Department of Defense position, policy, or decision. NR 347 TC 406 Z9 414 U1 32 U2 217 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2012 VL 35 IS 3 BP 121 EP 143 DI 10.1017/S0140525X11000446 PG 23 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 946ME UT WOS:000304355000001 PM 22617651 ER PT J AU Lindquist, KA Wager, TD Bliss-Moreau, E Kober, H Barrett, LF AF Lindquist, Kristen A. Wager, Tor D. Bliss-Moreau, Eliza Kober, Hedy Barrett, Lisa Feldman TI What are emotions and how are they created in the brain? Response SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article ID SUBTHALAMIC NUCLEUS STIMULATION; FUNCTIONAL NEUROIMAGING DATA; FACIAL EXPRESSIONS; BASIC EMOTIONS; PARKINSONS-DISEASE; PSYCHOLOGICAL CONSTRUCTION; INDIVIDUAL-DIFFERENCES; CULTURAL-DIFFERENCES; CONGENITALLY BLIND; ACCUMBENS DOPAMINE AB In our response, we clarify important theoretical differences between basic emotion and psychological construction approaches. We evaluate the empirical status of the basic emotion approach, addressing whether it requires brain localization, whether localization can be observed with better analytic tools, and whether evidence for basic emotions exists in other types of measures. We then revisit the issue of whether the key hypotheses of psychological construction are supported by our meta-analytic findings. We close by elaborating on commentator suggestions for future research. C1 [Lindquist, Kristen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lindquist, Kristen A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Wager, Tor D.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Bliss-Moreau, Eliza] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Bliss-Moreau, Eliza] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Kober, Hedy] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Lindquist, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM lindqukr@nmr.mgh.harvard.edu; tor.wager@colorado.edu; eblissmoreau@ucdavis.edu; hedy.kober@yale.edu; l.barrett@neu.edu FU NIH HHS [DP1 OD003312] NR 202 TC 11 Z9 15 U1 3 U2 56 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2012 VL 35 IS 3 BP 172 EP 202 DI 10.1017/S0140525X1100183X PG 31 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 946ME UT WOS:000304355000030 PM 22783560 ER PT J AU Strakowski, SM Adler, CM Almeida, J Altshuler, LL Blumberg, HP Chang, KKD DelBello, MP Frangou, S McIntosh, A Phillips, ML Sussman, JE Townsend, JD AF Strakowski, Stephen M. Adler, Caleb M. Almeida, Jorge Altshuler, Lori L. Blumberg, Hilary P. Chang, Kiki D. DelBello, Melissa P. Frangou, Sophia McIntosh, Andrew Phillips, Mary L. Sussman, Jessika E. Townsend, Jennifer D. TI The functional neuroanatomy of bipolar disorder: a consensus model SO BIPOLAR DISORDERS LA English DT Article DE amygdala; bipolar disorder; connectivity; functional magnetic resonance imaging (fMRI); neuroimaging; prefrontal cortex ID VENTRAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; WHITE-MATTER INTEGRITY; FACIAL EXPRESSIONS; AMYGDALA; ABNORMALITIES; FMRI; ADOLESCENTS; ACTIVATION; DEPRESSION AB Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, DelBello MP, Frangou S, McIntosh A, Phillips ML, Sussman JE, Townsend JD. The functional neuroanatomy of bipolar disorder: a consensus model. ?Bipolar Disord 2012: 14: 313325. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants work as well as that of others. Methods: Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. Results: Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity and prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially the amygdala. This developmental failure to establish healthy ventral prefrontallimbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. Conclusions: This model provides a potential substrate to guide future investigations and areas needing additional focus are identified. C1 [Strakowski, Stephen M.; Adler, Caleb M.; DelBello, Melissa P.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45267 USA. [Almeida, Jorge; Phillips, Mary L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Altshuler, Lori L.; Townsend, Jennifer D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Blumberg, Hilary P.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Chang, Kiki D.] Stanford Univ, Pediat Bipolar Disorders Res Program, Div Child & Adolescent Psychiat, Dept Psychiat & Behav Sci,Sch Med, Stanford, CA 94305 USA. [Frangou, Sophia] Kings Coll London, Sect Neurobiol Psychosis, Dept Psychosis Studies, Inst Psychiat, London WC2R 2LS, England. [McIntosh, Andrew; Sussman, Jessika E.] Univ Edinburgh, Div Psychiat, Sch Mol & Clin Med, Edinburgh, Midlothian, Scotland. [Phillips, Mary L.] Cardiff Univ Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. RP Strakowski, SM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 260 Stetson Suite 3200, Cincinnati, OH 45267 USA. EM stephen.strakowski@uc.edu RI McIntosh, Andrew/B-9379-2008; Frangou, Sophia/A-2672-2013; Almeida, Jorge/O-5185-2014 OI McIntosh, Andrew/0000-0002-0198-4588; Almeida, Jorge/0000-0002-1213-1986 FU NIH [P50 MH077138, R01 MH076971, R01 MH088371, 2R01MH070902, 1RC1MH088366, R01MH069747, 5R21MH075944, 1K24MH001848, 1R01MH084955, R01 MH077047, R01 MH080973, R01 MH078043] FX This workgroup was supported in part by the Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA. This manuscript was supported in part by NIH grants P50 MH077138 (SMS); R01 MH076971 and R01 MH088371 (MLP); 2R01MH070902, 1RC1MH088366, and R01MH069747 (HPB); 5R21MH075944, 1K24MH001848, and 1R01MH084955 (LLA); R01 MH077047 (KDC); R01 MH080973 (MPD); and R01 MH078043 (CMA). NR 72 TC 146 Z9 150 U1 7 U2 31 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 2012 VL 14 IS 4 BP 313 EP 325 DI 10.1111/j.1399-5618.2012.01022.x PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 947PE UT WOS:000304441200001 PM 22631617 ER PT J AU Townsend, J Altshuler, LL AF Townsend, Jennifer Altshuler, Lori L. TI Emotion processing and regulation in bipolar disorder: a review SO BIPOLAR DISORDERS LA English DT Review DE amygdala; bipolar disorder; emotion processing; emotion regulation; functional neuroimaging; vlPFC ID INCREASED AMYGDALA ACTIVATION; FACIAL AFFECT RECOGNITION; MEDIAL PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; NEGATIVE EMOTION; MOOD DISORDERS; RHESUS-MONKEY; VOLUNTARY SUPPRESSION; ORBITOFRONTAL CORTEX; COGNITIVE CONTROL AB Townsend J, Altshuler LL. Emotion processing and regulation in bipolar disorder: a review. ?Bipolar Disord 2012: 14: 326339. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BP) is characterized by a dysfunction of mood, alternating between states of mania/hypomania and depression. Thus, the primary abnormality appears to be an inability to regulate emotion, the result of which is emotional extremes. The purpose of this paper is to review the current functional magnetic resonance imaging (fMRI) literature on adult patients with BP using emotion processing or regulation paradigms. Methods: A search was conducted on PubMed using the keywords: bipolar disorder, fMRI, mania, bipolar depression, bipolar euthymia, emotion, and amygdala. Only those studies that were conducted in adult patients using an emotion activation task were included in the final review. Results: Using tasks that assess neural functioning during emotion processing and emotion regulation, many fMRI studies have examined BP subjects during mania and euthymia. Fewer fMRI studies have been conducted during depression, and fewer still have included the same subjects in multiple mood states. Despite these limitations, these studies have demonstrated specific abnormalities in frontallimbic regions. Using a variety of paradigms, investigators have specifically evaluated the amygdala (a structure within the limbic system known to be critical for emotion) and the prefrontal cortex (PFC) (a region known to have a regulatory function over the limbic system). Conclusions: These investigations reveal that amygdala activation varies as a function of mood state, while the PFC remains persistently hypoactivated across mood states. Emotional dysregulation and lability in mania and depression may reflect disruption of a frontallimbic functional neuroanatomical network. C1 [Townsend, Jennifer; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Townsend, Jennifer; Altshuler, Lori L.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Forest Laboratories; Sepracor; Eli Lilly Co. FX LLA has received past funding from Forest Laboratories (advisory board honoraria, March 2008), Sepracor (advisory board honoraria, January 2010), and Eli Lilly & Co. (consultant, September 2010). JT does not have any commercial associations that might pose a conflict of interest in connection with this manuscript. NR 117 TC 91 Z9 93 U1 12 U2 63 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 2012 VL 14 IS 4 BP 326 EP 339 DI 10.1111/j.1399-5618.2012.01021.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 947PE UT WOS:000304441200002 PM 22631618 ER PT J AU Townsend, JD Bookheimer, SY Foland-Ross, LC Moody, TD Eisenberger, NI Fischer, JS Cohen, MS Sugar, CA Altshuler, LL AF Townsend, Jennifer D. Bookheimer, Susan Y. Foland-Ross, Lara C. Moody, Teena D. Eisenberger, Naomi I. Fischer, Jeffrey S. Cohen, Mark S. Sugar, Catherine A. Altshuler, Lori L. TI Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; fMRI; orbitofrontal cortex; response inhibition; striatum ID MEDIAL PREFRONTAL CORTEX; BRAIN ACTIVATION; I DISORDER; FMRI; MANIA; ABNORMALITIES; MONKEYS; INTERFERENCE; IMPULSIVITY; DYSFUNCTION AB Townsend JD, Bookheimer SY, Foland-Ross LC, Moody TD, Eisenberger NI, Fischer JS, Cohen MS, Sugar CA, Altshuler LL. Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task. ?Bipolar Disord 2012: 14: 442450. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: The inferior frontal corticalstriatal network plays an integral role in response inhibition in normal populations. While inferior frontal cortex (IFC) impairment has been reported in mania, this study explored whether this dysfunction persists in euthymia. Methods: Functional magnetic resonance imaging (fMRI) activation was evaluated in 32 euthymic patients with bipolar I disorder and 30 healthy subjects while performing the Go/NoGo response inhibition task. Behavioral data were collected to evaluate accuracy and response time. Within-group and between-group comparisons of activation were conducted using whole-brain analyses to probe significant group differences in neural function. Results: Both groups activated bilateral IFC. However, between-group comparisons showed a significantly reduced activation in this brain region in euthymic patients with bipolar disorder compared to healthy subjects. Other frontal and basal ganglia regions involved in response inhibition were additionally significantly reduced in bipolar disorder patients, in both the medicated and the unmedicated subgroups. No areas of greater activation were observed in bipolar disorder patients versus healthy subjects. Conclusions: Bipolar disorder patients, even during euthymia, have a persistent reduction in activation of brain regions involved in response inhibition, suggesting that reduced activation in the orbitofrontal cortex and striatum is not solely related to the state of mania. These findings may represent underlying trait abnormalities in bipolar disorder. C1 [Townsend, Jennifer D.; Bookheimer, Susan Y.; Moody, Teena D.; Fischer, Jeffrey S.; Cohen, Mark S.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.] Univ Calif Los Angeles, David Geffen Sch Med, Lab NeuroImaging, Dept Neurol, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Moody, Teena D.; Sugar, Catherine A.; Altshuler, Lori L.] Univ Calif Los Angeles, Sch Publ Hlth, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Eisenberger, Naomi I.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Psychol, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU Stanley Medical Research Institute; National Alliance for Research on Schizophrenia and Depression; National Institute of Mental Health [K24 MH001848, R21 MH075944, 5F31MH078556]; National Center for Research Resources [RR12169, RR13642, RR00865]; Forest Laboratories; Sepracor; Eli Lilly Co. FX This work was supported by The Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, the National Institute of Mental Health (K24 MH001848, R21 MH075944 and 5F31MH078556), and the National Center for Research Resources (RR12169, RR13642 and RR00865). The authors also wish to thank the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, The Ahmanson Foundation, the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, and the Northstar Fund for generous support.; LLA has received past funding from Forest Laboratories (advisory board honoraria, March 2008), Sepracor (advisory board honoraria, January 2010), and Eli Lilly & Co. (consultant, September 2010). JDT, SYB, LCF-R, TDM, NIE, JSF, MSC, and CAS do not have any commercial associations that might pose a conflict of interest in connection with this manuscript. NR 38 TC 26 Z9 26 U1 3 U2 10 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 2012 VL 14 IS 4 BP 442 EP 450 DI 10.1111/j.1399-5618.2012.01020.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 947PE UT WOS:000304441200008 PM 22631623 ER PT J AU Gow, DW AF Gow, David W., Jr. TI The cortical organization of lexical knowledge: A dual lexicon model of spoken language processing SO BRAIN AND LANGUAGE LA English DT Review DE Lexicon; Language; Spoken word recognition; Lexical access; Speech perception; Speech production; Neuroimaging; Aphasia; Dual stream model; Localization ID EVENT-RELATED FMRI; ANTERIOR TEMPORAL CORTEX; WORD MEANING DEAFNESS; TRANSCORTICAL SENSORY APHASIA; VOICE-ONSET TIME; SPEECH-PERCEPTION; CONDUCTION APHASIA; SENTENCE COMPREHENSION; PAST-TENSE; WORKING-MEMORY AB Current accounts of spoken language assume the existence of a lexicon where wordforms are stored and interact during spoken language perception, understanding and production. Despite the theoretical importance of the wordform lexicon, the exact localization and function of the lexicon in the broader context of language use is not well understood. This review draws on evidence from aphasia, functional imaging, neuroanatomy, laboratory phonology and behavioral results to argue for the existence of parallel lexica that facilitate different processes in the dorsal and ventral speech pathways. The dorsal lexicon, localized in the inferior parietal region including the supramarginal gyrus, serves as an interface between phonetic and articulatory representations. The ventral lexicon, localized in the posterior superior temporal sulcus and middle temporal gyrus, serves as an interface between phonetic and semantic representations. In addition to their interface roles, the two lexica contribute to the robustness of speech processing. (C) 2012 Elsevier Inc. All rights reserved. C1 [Gow, David W., Jr.] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. [Gow, David W., Jr.] Salem State Univ, Dept Psychol, Salem, MA 01970 USA. [Gow, David W., Jr.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gow, David W., Jr.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Gow, DW (reprint author), Cognit Behav Neurol Grp, 175 Cambridge St,Suite S340, Boston, MA 02114 USA. EM gow@helix.mgh.harvard.edu FU National Institute of Deafness and Communicative Disorders [R01 DC003108] FX I would like to thank David Caplan, Catherine Stoodley, and Joshua Levy for their feedback during the preparation of this manuscript, and Matt Davis and Greg Hickok for their thoughtful reviews of an earlier version of this manuscript. This work was supported by the National Institute of Deafness and Communicative Disorders (R01 DC003108). I have no conflicts of interest to declare. NR 199 TC 48 Z9 48 U1 3 U2 51 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JUN PY 2012 VL 121 IS 3 BP 273 EP 288 DI 10.1016/j.bandl.2012.03.005 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 946GO UT WOS:000304339700011 PM 22498237 ER PT J AU Togsverd-Bo, K Haak, CS Thaysen-Petersen, D Wulf, HC Anderson, RR Haedesdal, M AF Togsverd-Bo, K. Haak, C. S. Thaysen-Petersen, D. Wulf, H. C. Anderson, R. R. Haedesdal, M. TI Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID TOPICAL METHYL AMINOLEVULINATE; PROTOPORPHYRIN-IX; 5-AMINOLEVULINIC ACID; DOUBLE-BLIND; RED-LIGHT; FLUORESCENCE; MULTICENTER; LASER; FACE; SKIN AB Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field-cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. Objectives To evaluate efficacy and safety of AFXL-assisted PDT (AFXL-PDT) compared with conventional PDT in field-directed treatment of AK. Methods Fifteen patients with a total of 212 AKs (severity grade I-III) in field-cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL-PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0 12 mm spot, 5% density, single pulse (UltraPulse (R), DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U. S. A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light-emitting diode light at 37 J cm(-2). Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. Results At 3-month follow-up, AFXL-PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II-III AK was 88% after AFXL-PDT compared with 59% after PDT (P = 0.02). In grade I AK, 100% of lesions cleared after AFXL-PDT compared with 80% after PDT (P = 0.04). AFXL-PDT treated skin responded with significantly fewer new AK lesions (AFXL-PDT n = 3, PDT n = 11; P = 0.04) and more improved photoageing (moderate vs. minor improvement, P = 0.007) than PDT-treated skin. Pain scores during illumination (6.5 vs. 5.4; P = 0.02), erythema and crusting were more intense, and long-term pigmentary changes more frequent from AFXL-PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL-pretreated skin [7528 vs. 12 816 arbitrary units (AU); P = 0.003] and photobleached to equal intensities after illumination (AFXL-PDT 595 AU, PDT 454 AU; P = 0.59). Conclusions AFXL-PDT is more effective than conventional PDT for treatment of AK in field-cancerized skin. C1 [Togsverd-Bo, K.; Haak, C. S.; Thaysen-Petersen, D.; Wulf, H. C.; Haedesdal, M.] Univ Copenhagen, Dept Dermatol, Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. [Anderson, R. R.; Haedesdal, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Togsverd-Bo, K (reprint author), Univ Copenhagen, Dept Dermatol, Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. EM ktogsverdbo@dadlnet.dk FU Department of Dermatology, Bispebjerg Hospital, University of Copenhagen; A. P. Moller Foundation for the Advancement of Medical Science. Lumenis Inc. (Santa Clara, CA, U.S.A.); Galderma FX The study was funded by Department of Dermatology, Bispebjerg Hospital, University of Copenhagen and A. P. Moller Foundation for the Advancement of Medical Science. Lumenis Inc. (Santa Clara, CA, U.S.A.) lent the ablative fractional CO2 laser but had no role in the design or conduct of the trial and had no access to study data nor the preparation of the manuscript.; K.T.-B. has received a travelling grant from Galderma. C. S. H. and D. T.-P. have no disclosures. H. C. W. has received fees for speaking and a travelling grant from Galderma. R. R. A. is a consultant for Galderma (unrelated to this study). M. H. has received fees from Galderma for speaking and is on the advisory board for Galderma International regarding photodynamic therapy of organ transplant recipients. NR 31 TC 59 Z9 64 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUN PY 2012 VL 166 IS 6 BP 1262 EP 1269 DI 10.1111/j.1365-2133.2012.10893.x PG 8 WC Dermatology SC Dermatology GA 950QV UT WOS:000304664700017 PM 22348388 ER PT J AU Bae, J Song, WH Smith, R Daley, J Tai, YT Anderson, KC Munshi, NC AF Bae, Jooeun Song, Weihua Smith, Robert Daley, John Tai, Yu-Tzu Anderson, Kenneth C. Munshi, Nikhil C. TI A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Multiple myeloma; CS1; epitope; peptide vaccine ID HUMANIZED MONOCLONAL-ANTIBODY; PLASMA-CELL DIFFERENTIATION; RECEPTOR; EXPRESSION; LEUKEMIA; IMMUNOTHERAPY; THALIDOMIDE; APOPTOSIS; PARADIGM; VACCINES AB The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA-A2+ immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes (CTL) against HLA-A2+ MM cells. We identified a novel immunogenic HLA-A2-specific CS1239-247 (SLFVLGLFL) peptide, which induced CS1-specific CTL (CS1-CTL) to MM cells. The CS1-CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naive CTL. CS1239-247 peptide-specific CD8+ T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and ?-interferon (IFN-?) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO+CCR7-/CD3+CD8+) within CS1-CTL showed a higher level of CD107a degranulation and IFN-? production as compared to effector cells (CD45RO-CCR7-/CD3+CD8+) against HLA-A2+ primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA-A2-specific CS1239-247 peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy. C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Song, Weihua; Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU National Institutes of Health [RO1-124929, P50-100007, PO1155258, RO1-50947, PO1-155258, P50-100707, PO1-78378, RO1-129295]; American Cancer Society; Department of Veteran's Affairs [RO1-50947] FX This work was supported in part by grants from the National Institutes of Health Grants RO1-124929 to Dr. Nikhil C. Munshi, P50-100007, PO1-78378 and PO1155258 to Dr. Nikhil C. Munshi and Dr. Kenneth C. Anderson and RO1-50947 to Dr. Kenneth C. Anderson. Dr. Anderson is an American Cancer Society Clinical Research Professor. We also acknowledge the generous support of the Stewart Nagler Research Fund. NIH grants PO1-155258 (NCM); P50-100707 (KCA), and PO1-78378 (KCA), RO1-129295 and Department of Veteran's Affairs merit review award (NCM) and RO1-50947 (KCA). NR 45 TC 12 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2012 VL 157 IS 6 BP 687 EP 701 DI 10.1111/j.1365-2141.2012.09111.x PG 15 WC Hematology SC Hematology GA 947PI UT WOS:000304441600006 PM 22533610 ER PT J AU Leiba, M Jakubikova, J Klippel, S Mitsiades, CS Hideshima, T Tai, YT Leiba, A Pines, M Richardson, PG Nagler, A Anderson, KC AF Leiba, Merav Jakubikova, Jana Klippel, Steffen Mitsiades, Constantine S. Hideshima, Teru Tai, Yu-Tzu Leiba, Adi Pines, Mark Richardson, Paul G. Nagler, Arnon Anderson, Kenneth C. TI Halofuginone inhibits multiple myeloma growth in vitro and in vivo and enhances cytotoxicity of conventional and novel agents SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Halofuginone; TGF-ss; JNK; c-jun; p-53 ID CELL-GROWTH; HEPATOCELLULAR-CARCINOMA; MOLECULAR-MECHANISMS; ANTITUMOR-ACTIVITY; BONE-MARROW; P38 MAPK; APOPTOSIS; PATHWAYS; JNK; ANGIOGENESIS AB Multiple Myeloma (MM), a malignancy of plasma cells, remains incurable despite the use of conventional and novel therapies. Halofuginone (HF), a synthetic derivative of quinazolinone alkaloid, has recently been shown to have anti-cancer activity in various preclinical settings. This study demonstrated the anti-tumour activity of HF against a panel of human MM cell lines and primary patient-derived MM cells, regardless of their sensitivity to conventional therapy or novel agents. HF showed anti-MM activity in vivo using a myeloma xenograft mouse model. HF suppressed proliferation of myeloma cells alone and when co-cultured with bone marrow stromal cells. Similarly, HF induced apoptosis in MM cells even in the presence of insulin-like growth factor 1 or interleukin 6. Importantly, HF, even at high doses, did not induce cytotoxicity against CD40 activated peripheral blood mononuclear cells from normal donors. HF treatment induced accumulation of cells in the G0/G1 cell cycle and induction of apoptotic cell death associated with depletion of mitochondrial membrane potential; cleavage of poly (ADP-ribose) polymerase and caspases-3, 8 and 9 as well as down-regulation of anti-apoptotic proteins including Mcl-1 and X-IAP. Multiplex analysis of phosphorylation of diverse components of signalling cascades revealed that HF induced changes in P38MAPK activation; increased phosphorylation of c-jun, c-jun NH(2)-terminal kinase (JNK), p53 and Hsp-27. Importantly, HF triggered synergistic cytotoxicity in combination with lenalidomide, melphalan, dexamethasone, and doxorubicin. Taken together, these preclinical studies provide the preclinical framework for future clinical studies of HF in MM. C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [Leiba, Merav; Jakubikova, Jana; Klippel, Steffen; Mitsiades, Constantine S.; Hideshima, Teru; Tai, Yu-Tzu; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma, Boston, MA 02215 USA. [Leiba, Merav; Nagler, Arnon] Chaim Sheba Med Ctr, Div Haematol & Bone Marrow Transplantat, IL-52621 Tel Hashomer, Israel. [Jakubikova, Jana] Slovak Acad Sci, Canc Res Inst, Dept Tumour Immunol, Bratislava, Slovakia. [Pines, Mark] Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 430 Brookline Ave, Boston, MA 02215 USA. EM Kenneth_Anderson@dfci.harvard.edu FU NCI NIH HHS [P50 CA100707, R01 CA050947] NR 52 TC 16 Z9 23 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2012 VL 157 IS 6 BP 718 EP 731 DI 10.1111/j.1365-2141.2012.09120.x PG 14 WC Hematology SC Hematology GA 947PI UT WOS:000304441600009 PM 22533681 ER PT J AU Tomasetti, C AF Tomasetti, Cristian TI On the Probability of Random Genetic Mutations for Various Types of Tumor Growth SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article DE Tumor growth; Genetic mutations; Drug resistance; Stem cells; Ordinary differential equations; Branching processes ID CHRONIC MYELOID-LEUKEMIA; DRUG-RESISTANCE; STEM-CELLS; MATHEMATICAL-MODELS; CANCER-CHEMOTHERAPY; AMPLIFICATION; DIVISION; SENSITIVITY; COMBINATION; DYNAMICS AB In this work, we consider the problem of estimating the probability for a specific random genetic mutation to be present in a tumor of a given size. Previous mathematical models have been based on stochastic methods where the tumor was assumed to be homogeneous and, on average, growing exponentially. In contrast, we are able to obtain analytical results for cases where the exponential growth of cancer has been replaced by other, arguably more realistic types of growth of a heterogeneous tumor cell population. Our main result is that the probability that a given random mutation will be present by the time a tumor reaches a certain size, is independent of the type of curve assumed for the average growth of the tumor, at least for a general class of growth curves. The same is true for the related estimate of the expected number of mutants present in a tumor of a given size, if mutants are indeed present. C1 [Tomasetti, Cristian] Harvard Univ, Dept Biostat, Boston, MA 02215 USA. [Tomasetti, Cristian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Tomasetti, C (reprint author), Harvard Univ, Dept Biostat, CLS11007,450 Brookline Ave, Boston, MA 02215 USA. EM cristian@jimmy.harvard.edu OI Tomasetti, Cristian/0000-0003-3277-4804 FU National Institute of Health [T32 CA009337]; National Science Foundation/National Institute of General Medical Sciences [DMS-0758374]; National Cancer Institute [R01CA130817] FX The author wishes to thank Professor Dmitry Dolgopyat for his helpful discussions and the reviewers for their valuable comments. The work of CT was supported in part by the National Institute of Health under Grant T32 CA009337, by the joint National Science Foundation/National Institute of General Medical Sciences program under Grant DMS-0758374 and by the National Cancer Institute under Grant R01CA130817. NR 36 TC 6 Z9 6 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD JUN PY 2012 VL 74 IS 6 BP 1379 EP 1395 DI 10.1007/s11538-012-9717-1 PG 17 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 946ZD UT WOS:000304395500005 PM 22311065 ER PT J AU Berkey, CS Tamimi, RM Rosner, B Frazier, AL Colditz, GA AF Berkey, Catherine S. Tamimi, Rulla M. Rosner, Bernard Frazier, A. Lindsay Colditz, Graham A. TI Young women with family history of breast cancer and their risk factors for benign breast disease SO CANCER LA English DT Article DE adolescents; preteens; family history; alcohol; body mass index; height growth spurt; peak height growth velocity; age at menarche; benign breast disease; breast cancer ID ALCOHOL-CONSUMPTION; NURSES HEALTH; GROWTH; AGE; ADOLESCENTS; COHORT; GIRLS AB BACKGROUND: Breast cancer (BC) patients wonder how their daughters might reduce their risk. The authors investigated childhood/adolescent risk factors for benign breast disease (BBD), a well-documented risk factor for BC, among girls with a family history. METHODS: GUTS (the Growing Up Today Study) includes females, aged 9 to 15 years in 1996, who completed annual questionnaires during 1996 to 2001, then in 2003, 2005, and 2007. Participants provided information regarding alcohol, menarche, height, and body mass index (BMI; kg/m2). Peak height growth velocity (PHV; in./y) was estimated from longitudinal heights. On 2005-2007 surveys, 6888 women (18-27 years old) reported whether they were diagnosed with biopsy-confirmed BBD (n = 67 cases); 6741 women (noncases) reported no BBD. Participants' mothers reported their own biopsy-confirmed BBD and BC, and BC in their sisters and mothers. Stratified by family history, logistic models investigated BBD risk factors. RESULTS: Young women whose mothers or aunts had BC were more likely to be diagnosed with BBD (odds ratio [OR], 2.34; P = .01), as were those with maternal BBD (OR, 1.59; P = .095). Adolescents with BC family history (mother, aunt, grandmother) who consumed alcohol (7 drinks/wk) doubled their BBD risk (OR, 2.28; P = .01), similar to those with maternal BBD (OR, 1.96; P = .02). Girls whose mother or aunt had BC saw their BBD risk elevated with higher PHV (OR, 1.82 [inch/yr]; P = .05). Among girls with no family history, BBD risk appeared to be related to other factors: childhood BMI, adolescent waist circumference, and adult height. CONCLUSIONS: Adolescents with family history may reduce their risk by avoiding alcohol. Separate risk factors were observed among girls with family history versus girls with no family history, possibly reflecting different causes of BC. Cancer 2011;. (c) 2011 American Cancer Society. C1 [Berkey, Catherine S.; Tamimi, Rulla M.; Rosner, Bernard; Frazier, A. Lindsay] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Berkey, Catherine S.; Tamimi, Rulla M.; Rosner, Bernard; Frazier, A. Lindsay] Harvard Univ, Sch Med, Boston, MA USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Alvin J Siteman Canc Ctr, Sch Med, St Louis, MO USA. RP Berkey, CS (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM Catherine.Berkey@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Institutes of Health (Bethesda, Md) [DK46834]; Breast Cancer Research foundation (New York, New York); American Institute for Cancer Research; American Cancer Society FX Grant DK46834 (principal investigator [PI], G. A. C.) from the National Institutes of Health (Bethesda, Md) funded the initiation of the cohort and the collection/management of the data during early years of follow-up. The Breast Cancer Research foundation (New York, New York) funded the design, conduct, and analysis of this specific article (PI, G. A. C.). Neither sponsor was involved in the preparation, review, or approval of the article. A. L. F. was supported by an award from the American Institute for Cancer Research. G. A. C. was supported in part by an American Cancer Society Clinical Research Professorship. NR 33 TC 12 Z9 12 U1 0 U2 5 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 2012 VL 118 IS 11 BP 2796 EP 2803 DI 10.1002/cncr.26519 PG 8 WC Oncology SC Oncology GA 944HA UT WOS:000304188700004 PM 22083563 ER PT J AU Choy, E Hornicek, F MacConaill, L Harmon, D Tariq, Z Garraway, L Duan, ZF AF Choy, Edwin Hornicek, Francis MacConaill, Laura Harmon, David Tariq, Zeeshan Garraway, Levi Duan, Zhenfeng TI High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes SO CANCER LA English DT Article DE genotyping; osteosarcoma; OncoMap; phosphoinositide-3-kinase; catalytic; alpha polypeptide; mutation ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; IMATINIB MESYLATE; STAT3 PATHWAY; THERAPY; GENOME; RESISTANCE; INHIBITION; EXPRESSION; APOPTOSIS AB BACKGROUND: The identification of new genes that are mutated in osteosarcomas is critical to developing a better understanding of the molecular pathogenesis of this disease and discovering new targets for therapeutic development. METHODS: The authors identified somatic nonsynonymous coding mutations in oncogenes associated with human cancers and hotspot mutations from tumor suppressor genes that were either well described in the literature or observed multiple times in human cancer sequencing efforts. Then, 961 mutations in 89 genes were systematically characterized across 98 osteosarcoma tumor samples and cell lines. All identified mutations were replicated on an independent platform using homogeneous mass extend matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: In total, 14 mutations were identified in at least 1 osteosarcoma tumor sample or cell line. Some of the genetic changes identified were in tumor suppressor genes previously identified as altered in osteosarcoma: p53 (arginine -> histidine at codon 273 [R273H], R -> cysteine at codon 723 [R273C], and tyrosine -> C at codon 163 [Y163C]) and retinoblastoma 1 (RB1) (glutamic acid ->* at codon 137 [E137*]). Notably, multiple mutations were identified in phosphoinositide-3-kinase (PI3K), catalytic, alpha polypeptide (PIK3CA) (H1047R, E -> lysine at codon 545 [E545K], and H -> proline at codon 701 [H701P]) that were not observed previously in osteosarcoma. In addition, mutations in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (glycine -> serine at codon 12 [G12S]); cubilin (CUBN) (isolucine -> valine at codon 3189 [I3189V]; observed in 2 separate tumor samples); cadherin 1, type 1, epithelial (CDH1) (alanine -> threonine at codon 617 [A617T]; observed in 2 separate tumor samples); catenin (cadherin-associated protein), beta 1, 88 kDa (CTNNB1) (asparagine -> S at codon 287 [N287S]); and fibrous sheath CABYR binding protein (FSCB) (S -> leucine at codon 775 [S775L]) were observed. CONCLUSIONS: In this largest mutational profiling of osteosarcoma to date, the authors identified for the first time several mutations involving the PI3K pathway, adding osteosarcoma to the growing list of malignancies with PI3K mutations. In addition, they initiated a mutational map detailing DNA sequence changes across a variety of osteosarcoma subtypes and offered new candidates for therapeutic targeting. Cancer 2011. (c) 2011 American Cancer Society. C1 [Choy, Edwin; Harmon, David] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Choy, Edwin; Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Ctr Canc, Boston, MA 02114 USA. [MacConaill, Laura; Garraway, Levi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [MacConaill, Laura; Garraway, Levi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tariq, Zeeshan] Univ Toledo, Dept Med, Med Ctr, Toledo, OH 43606 USA. RP Choy, E (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA. EM echoy@partners.org OI Duan, Zhenfeng/0000-0002-8543-083X; Choy, Edwin/0000-0001-9896-8084 FU Jennifer Hunter Yates Foundation; Kenneth Stanton Osteosarcoma Research Fund; Cassandra Moseley Berry Sarcoma Endowed Fund; Gategno Fund; Wechsler Fund; Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Institutes of Health) [1KL2RR025757-01]; Harvard University; Amgen; Sanofi-Aventis; Novartis; Pharmacyclics FX This project was supported in part by the Jennifer Hunter Yates Foundation, the Kenneth Stanton Osteosarcoma Research Fund, the Cassandra Moseley Berry Sarcoma Endowed Fund, the Gategno and Wechsler Funds, and the KL2 Medical Research Investigator Training (MeRIT) grant awarded to E.C. through Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Institutes of Health grant 1KL2RR025757-01), and by financial contributions from Harvard University and its affiliated academic health care centers.; E.C. has received financial and research support from Amgen, Sanofi-Aventis, Novartis, and Pharmacyclics. L. G. is a consultant for Novartis and Foundation Medicine and an equity holder in Foundation Medicine. NR 51 TC 30 Z9 31 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2012 VL 118 IS 11 BP 2905 EP 2914 DI 10.1002/cncr.26617 PG 10 WC Oncology SC Oncology GA 944HA UT WOS:000304188700016 PM 22006429 ER PT J AU Kumar, A Vanderplas, A LaCasce, AS Rodriguez, MA Crosby, AL Lepisto, E Czuczman, MS Nademanee, A Niland, J Gordon, LI Millenson, M Zelenetz, AD Friedberg, JW Abel, GA AF Kumar, Anita Vanderplas, Ann LaCasce, Ann S. Rodriguez, Maria A. Crosby, Allison L. Lepisto, Eva Czuczman, Myron S. Nademanee, Auayporn Niland, Joyce Gordon, Leo I. Millenson, Michael Zelenetz, Andrew D. Friedberg, Jonathan W. Abel, Gregory A. TI Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era SO CANCER LA English DT Article DE diffuse large B-cell lymphoma; central nervous system prophylaxis; propensity score analysis; health services research ID NON-HODGKINS-LYMPHOMA; STUDY-GROUP DSHNHL; RISK-FACTORS; ELDERLY-PATIENTS; INTRATHECAL CHEMOTHERAPY; AGGRESSIVE LYMPHOMA; INTERMEDIATE-GRADE; CHOP CHEMOTHERAPY; CNS PROPHYLAXIS; RELAPSE AB BACKGROUND: Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. The objective of this study was to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy using the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at 7 participating centers. METHODS: Patients who were eligible for this analysis presented with newly diagnosed DLBCL between January 2001 and July 2008, had no evidence of baseline CNS disease, and had received R-CHOP within 180 days of diagnosis. The authors assessed incidence and covariates of prophylaxis, prophylaxis modality, and, using propensity score analysis, outcomes such as overall survival. RESULTS: Of 989 eligible patients, 117 received CNS prophylaxis (11.8%), most intrathecally (71.8%). Involvement of bone marrow, other high-risk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis (all P < .0001). At a median follow-up of 2.5 years, there were 20 CNS recurrences (2% [95% confidence interval, 1.1%-2.9%]) among all patients, and overall survival was not affected by prophylaxis. CONCLUSIONS: Given the overall low rate of CNS recurrence and lack of prophylaxis-associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era. Cancer 2011. (c) 2011 American Cancer Society. C1 [Crosby, Allison L.; Abel, Gregory A.] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. [Vanderplas, Ann; Niland, Joyce] City Hope Natl Med Ctr, Div Informat Sci, Duarte, CA 91010 USA. [Nademanee, Auayporn] City Hope Natl Med Ctr, Div Hematol & Bone Marrow Transplantat, Duarte, CA 91010 USA. [LaCasce, Ann S.] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, Boston, MA 02115 USA. [Rodriguez, Maria A.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Div Med, Buffalo, NY 14263 USA. [Gordon, Leo I.] Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL USA. [Millenson, Michael] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, New York, NY 10021 USA. [Friedberg, Jonathan W.] James P Wilmot Canc Ctr, Div Hematol Oncol, Rochester, NY USA. [Lepisto, Eva] Natl Comprehens Canc Network, NCCN VP Technol Res & Dev, Ft Washington, MD USA. [Kumar, Anita; LaCasce, Ann S.; Abel, Gregory A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu NR 27 TC 32 Z9 33 U1 0 U2 3 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 2012 VL 118 IS 11 BP 2944 EP 2951 DI 10.1002/cncr.26588 PG 8 WC Oncology SC Oncology GA 944HA UT WOS:000304188700020 PM 22006274 ER PT J AU Corey, KE Lai, M Gelrud, LG Misdraji, J Barlow, LL Zheng, H Andersson, KL Thiim, M Pratt, DS Chung, RT AF Corey, Kathleen E. Lai, Michelle Gelrud, Louis G. Misdraji, Joseph Barlow, Lydia L. Zheng, Hui Andersson, Karin L. Thiim, Michael Pratt, Daniel S. Chung, Raymond T. TI Non-High-Density Lipoprotein Cholesterol as a Biomarker for Nonalcoholic Steatohepatitis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Diagnostic; Nonalcoholic Fatty Liver Disease; Blood Test; Clinical Trial ID FATTY LIVER-DISEASE; NON-HDL CHOLESTEROL; TRIGLYCERIDE SYNTHESIS; HEPATIC STEATOSIS; RISK; ATORVASTATIN AB BACKGROUND & AIMS: There are no clinically available biomarkers for nonalcoholic steatohepatitis (NASH); differentiating between steatosis and NASH requires histologic evaluation. Noninvasive methods are needed to replace liver biopsy and its associated risks. Production of very low density lipoprotein (VLDL) contributes to the development of NASH and might be used to distinguish steatosis from NASH. However, it is not possible to measure levels of VLDL directly in the clinic. Non-high-density lipoprotein-cholesterol (non-HDL-C) encompasses all apolipoprotein-B-containing lipoproteins, including VLDL, and can be calculated from standard lipid panels without additional cost. METHODS: We evaluated the ability of non-HDL-C to differentiate steatosis from NASH in a prospective study of 218 patients with suspected NASH (steatosis, n = 100 and NASH, n = 118). RESULTS: Patients with NASH had a trend toward increased levels of non-HDL-C, compared with those with steatosis (P = .08). However, among subjects not on lipid-lowering medications, those with NASH had significantly higher levels of non-HDL-C (144.6 mg/dL) than those with steatosis (129.3 mg/dL; P = .025). This difference remained significant when adjusted for levels of cholesterol and triglycerides, indicating that the difference results from increased levels of apolipoprotein B including VLDL. These findings were validated in a cohort of 40 patients with steatosis or NASH who were not taking lipid-lowering agents. The NASH group had significantly higher levels of non-HDL-C than the steatosis group (162.8 vs 145.9 mg/dL; P = .04). CONCLUSIONS: NASH is associated with significantly higher levels of non-HDL-C than steatosis in patients who do not take lipid-lowering agents. This low-cost biomarker could be used in noninvasive differentiation between steatosis and NASH. C1 [Corey, Kathleen E.; Barlow, Lydia L.; Andersson, Karin L.; Thiim, Michael; Pratt, Daniel S.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Hui; Chung, Raymond T.] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Corey, Kathleen E.; Lai, Michelle; Misdraji, Joseph; Zheng, Hui; Andersson, Karin L.; Thiim, Michael; Pratt, Daniel S.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Lai, Michelle] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Gelrud, Louis G.] Bon Secours Richmond Hlth Syst, Dept Internal Med, Richmond, VA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU American Association for the Study of Liver Disease; NIDDK [5K23DK83439-2]; NIH [DK078772] FX K.E.C. receives support from the American Association for the Study of Liver Disease. M.L. received support from the NIDDK K23 grant number 5K23DK83439-2. R.T.C. receives support from NIH DK078772. NR 28 TC 19 Z9 19 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 2012 VL 10 IS 6 BP 651 EP 656 DI 10.1016/j.cgh.2012.01.017 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 948QJ UT WOS:000304517400019 PM 22330232 ER PT J AU Saylor, PJ Escudier, B Michaelson, MD AF Saylor, Philip J. Escudier, Bernard Michaelson, M. Dror TI Importance of Fibroblast Growth Factor Receptor in Neovascularization and Tumor Escape from Antiangiogenic Therapy SO CLINICAL GENITOURINARY CANCER LA English DT Review DE Angiogenesis; Cell signaling; Renal cell carcinoma; Vascular endothelial growth factor receptor ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; TYROSINE KINASE INHIBITOR; ENDOTHELIAL-CELLS; IN-VITRO; INTERFERON-ALPHA; SUPPRESSOR GENE; BINDING PROTEIN; DOUBLE-BLIND; ANGIOGENESIS AB Therapeutic inhibition of pathways involved in angiogenesis has become the standard of care in renal cell carcinoma (RCC). Most currently available antiangiogenic agents inhibit the vascular endothelial growth factor (VEGF) pathway. Although these drugs have produced exciting benefits, some tumors do not respond to these agents. In addition most if not all tumors that initially respond will eventually develop resistance. Tumor escape from antiangiogenic therapy may include various signaling pathways that are involved in angiogenesis, including the fibroblast growth factor (FGF) signaling pathway. Emerging preclinical data suggest that FGF and VEGF act distinctly and synergistically to promote tumor vascularization. The current review discusses the role of FGF signaling in resistance to anti-VEGF therapies and outlines potential therapeutic implications. Clinical Genitourinary Cancer, Vol. 10, No. 2, 77-83 (c) 2012 Elsevier Inc. All rights reserved. C1 [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Escudier, Bernard] Inst Gustave Roussy, Villejuif, France. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org OI Michaelson, Dror/0000-0001-9249-6338 FU Novartis Pharmaceuticals FX Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. NR 80 TC 21 Z9 21 U1 0 U2 8 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2012 VL 10 IS 2 BP 77 EP 83 DI 10.1016/j.clgc.2012.01.010 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 944LG UT WOS:000304202600003 PM 22382009 ER PT J AU Liu, G Chen, YH DiPaola, R Carducci, M Wilding, G AF Liu, Glenn Chen, Yu-Hui DiPaola, Robert Carducci, Michael Wilding, George TI Phase II Trial of Weekly Ixabepilone in Men With Metastatic Castrate-Resistant Prostate Cancer (E3803): A Trial of the Eastern Cooperative Oncology Group SO CLINICAL GENITOURINARY CANCER LA English DT Article DE BMS-247550; Chemotherapy; Epothilone; Microtubule-inhibitor; NCT00087139; Version date; 2/20/2011 ID EPOTHILONE-B-ANALOG; ADVANCED SOLID TUMORS; ESTRAMUSTINE PHOSPHATE; WEEKLY DOCETAXEL; 1-HOUR INFUSION; CLINICAL-TRIALS; DAILY SCHEDULE; WORKING GROUP; BMS-247550; MITOXANTRONE AB Ixabepilone is an epothilone B analogue with activity in a variety of solid malignancies, including prostate cancer. The main dose-limiting toxicity of ixabepilone is myelosuppression when administered by using an every 3-week schedule. Here we evaluate the activity of a weekly ixabepilone in men with metastatic castrate-resistant prostate cancer to minimize hematologic toxicity. Purpose: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistant cancer cell lines. Here we report the activity and toxicity of ixabepilone, administered by using a weekly schedule, in men with metastatic castrate-resistant prostate cancer (CRPC). Experimental Design: Patients with metastatic CRPC received ixabepilone at 20 mg/m(2) intravenous weekly x 3, in 4-week cycles. This noncomparative study stratified patients to either a chemotherapy naive (CN), prior taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The primary endpoint was prostate-specific antigen response by using PCWG (Prostate Cancer Working Group) 1 criteria. Secondary endpoints included radiographic response when using RECIST (Response Evaluation Criteria In Solid Tumors). Results: In total, 124 patients were enrolled, of whom, 109 were eligible (35 CN, 42 Tax, and 32 TCx) for the primary response determination in this study. Prostate-specific antigen responses were seen in 12 (34.3%) of 35, 12 (28.6%) of 42, and 7 (21.9%) of 32 patients with the partial objective response in 5 (22.7%) of 22, 2 (8.0%) of 25, and 0 (0.0%) of 24 patients for the CN, Tax, and TCx arms, respectively. Significant (grade 3/4) neutropenia was seen in 6 (15.4%), 7 (14.6%), and 9 (25.0%); and grade 3/4 sensory neuropathy was seen in 8 (20.5%), 12 ( 25.0%), and 12 (33.3%) for CN, Tax, and TCx, respectively. Grade 3/4 thrombocytopenia was infrequent and seen in only one patient on the CN and the TCx arm. Conclusion: Ixabepilone was found to have an acceptable toxicity profile when administered by using a weekly schedule with less myelosuppression compared with prior studies when using the every 3-week schedule. Single-agent activity was observed and met prespecified activity levels for the Tax treated arm. Clinical Genitourinary Cancer, Vol. 10, No. 2, 99-105 (c) 2012 Published by Elsevier Inc. C1 [Liu, Glenn] Univ Wisconsin, Carbone Canc Ctr, Wisconsin Inst Med Res, Madison, WI 53705 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Boston, MA 02115 USA. [DiPaola, Robert] Canc Inst New Jersey, New Brunswick, NJ USA. [Carducci, Michael] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. RP Liu, G (reprint author), Univ Wisconsin, Carbone Canc Ctr, Wisconsin Inst Med Res, 1111 Highland Ave,Room 7051, Madison, WI 53705 USA. EM gxl@medicine.wisc.edu FU NCI NIH HHS [CA66636, U10 CA016116, CA107868, CA23318, U10 CA021076, U10 CA080775, CA21076, U10 CA066636, U10 CA023318, U10 CA021115, P30 CA016672, CA21115, U10 CA107868, CA16116, CA80775] NR 26 TC 12 Z9 12 U1 1 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2012 VL 10 IS 2 BP 99 EP 105 DI 10.1016/j.clgc.2012.01.009 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 944LG UT WOS:000304202600006 PM 22386239 ER PT J AU Calfee, CS Gallagher, D Abbott, J Thompson, BT Matthay, MA AF Calfee, Carolyn S. Gallagher, Diana Abbott, Jason Thompson, B. Taylor Matthay, Michael A. CA NHLBI ARDS Network TI Plasma angiopoietin-2 in clinical acute lung injury: Prognostic and pathogenetic significance SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; angiopoietin-2; biomarkers; endothelial injury; pulmonary edema; von Willebrand factor ID RESPIRATORY-DISTRESS-SYNDROME; VON-WILLEBRAND-FACTOR; CIRCULATING ANGIOPOIETIN-2; CRITICALLY-ILL; FACTOR ANTIGEN; MORTALITY; RISK; VENTILATION; PREDICTOR; SEPSIS AB Background: Angiopoietin-2 is a proinflammatory mediator of endothelial injury in animal models, and increased plasma angiopoietin-2 levels are associated with poor outcomes in patients with sepsis-associated acute lung injury. Whether angiopoietin-2 levels are modified by treatment strategies in patients with acute lung injury is unknown. Objectives: To determine whether plasma angiopoietin-2 levels are associated with clinical outcomes and affected by fluid management strategy in a broad cohort of patients with acute lung injury. Design, Setting, and Participants:Plasma levels of angiopoietin-2 and von Willebrand factor (a traditional marker of endothelial injury) were measured in 931 subjects with acute lung injury enrolled in a randomized trial of fluid liberal vs. fluid conservative management. Measurements and Main Results: The presence of infection (sepsis or pneumonia) as the primary acute lung injury risk factor significantly modified the relationship between baseline angiopoietin-2 levels and mortality (p = .01 for interaction). In noninfection-related acute lung injury, higher baseline angiopoietin-2 levels were strongly associated with increased mortality (odds ratio, 2.43 per 1-log increase in angiopoietin-2; 95% confidence interval, 1.57-3.75; p < .001). In infection-related acute lung injury, baseline angiopoietin-2 levels were similarly elevated in survivors and nonsurvivors; however, patients whose plasma angiopoietin-2 levels increased from day 0 to day 3 had more than double the odds of death compared with patients whose angiopoietin-2 levels declined over the same period of time (odds ratio, 2.29; 95% confidence interval, 1.54-3.43; p < .001). Fluid-conservative therapy led to a 15% greater decline in angiopoietin-2 levels from day 0 to day 3 (95% confidence interval, 4.6-24.8%; p = .006) compared with fluid-liberal therapy in patients with infection-related acute lung injury. In contrast, plasma levels of von Willebrand factor were significantly associated with mortality in both infection-related and noninfection-related acute lung injury and were not affected by fluid therapy. Conclusions: Unlike von Willebrand factor, plasma angiopoietin-2 has differential prognostic value for mortality depending on the presence or absence of infection as an acute lung injury risk factor. Fluid conservative therapy preferentially lowers plasma angiopoietin-2 levels over time and thus may be beneficial in part by decreasing endothelial inflammation. (Crit Care Med 2012; 40:1731-1737) C1 [Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Calfee, Carolyn S.; Abbott, Jason; Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Gallagher, Diana] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep, Boston, MA 02215 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. RP Calfee, CS (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. EM carolyn.calfee@ucsf.edu FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HR 46046-64, N01-HR-16146-54]; Flight Attendant Medical Research Institute; NCRR, a component of the NIH [KL2RR024130]; [HL090833]; [HL 51856] FX Supported, in part, by contracts (N01-HR 46046-64 and N01-HR-16146-54) with the National Heart, Lung, and Blood Institute (NHLBI). Dr. Calfee was supported by HL090833, by the Flight Attendant Medical Research Institute, and by KL2RR024130 from the NCRR, a component of the NIH. Dr. Matthay was supported by HL 51856. NR 21 TC 58 Z9 64 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2012 VL 40 IS 6 BP 1731 EP 1737 DI 10.1097/CCM.0b013e3182451c87 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 946EZ UT WOS:000304335600006 PM 22610178 ER PT J AU Wilcox, SR Bittner, EA Elmer, J Seigel, TA Nguyen, NTP Dhillon, A Eikermann, M Schmidt, U AF Wilcox, Susan R. Bittner, Edward A. Elmer, Jonathan Seigel, Todd A. Nguyen, Nicole Thuy P. Dhillon, Anahat Eikermann, Matthias Schmidt, Ulrich TI Neuromuscular blocking agent administration for emergent tracheal intubation is associated with decreased prevalence of procedure-related complications SO CRITICAL CARE MEDICINE LA English DT Article DE airway management; anoxia; emergency treatment; hypoxia; intubation; neuromuscular blockade ID INTENSIVE-CARE-UNIT; DIFFICULT AIRWAY MANAGEMENT; RAPID-SEQUENCE INTUBATION; ENDOTRACHEAL INTUBATION; MULTIPLE-CENTER; ROCURONIUM; INDUCTION; ANESTHESIA; SUCCINYLCHOLINE; SEVOFLURANE AB Background: Emergent intubation is associated with a high rate of complications. Neuromuscular blocking agents are routinely used in the operating room and emergency department to facilitate intubation. However, use of neuromuscular blocking agents during emergent airway management outside of the operating room and emergency department is controversial. We hypothesized that the use of neuromuscular blocking agents is associated with a decreased prevalence of hypoxemia and reduced rate of procedure-related complications. Methods: Five hundred sixty-six patients undergoing emergent intubations in two tertiary care centers, Massachusetts General Hospital, Boston, MA, and the University of California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA, were enrolled in a prospective, observational study. The 112 patients intubated during cardiopulmonary resuscitation were excluded, leaving 454 patients for analysis. All intubations were supervised by attendings trained in Critical Care Medicine. We measured intubating conditions, oxygen saturation during and 5 mins following intubation. We assessed the prevalence of procedure-related complications defined as esophageal intubation, traumatic intubation, aspiration, dental injury, and endobronchial intubation. Results: The use of neuromuscular blocking agents was associated with a lower prevalence of hypoxemia (10.1% vs. 17.4%, p = .022) and a lower prevalence of procedure-related complications (3.1% vs. 8.3%, p = .012). This association persisted in a multivariate analysis, which controlled for airway grade, sedation, and institution. Use of neuromuscular blocking agents was associated with significantly improved intubating conditions (laryngeal view, p = .014; number of intubation attempts, p = .049). After controlling for the number of intubation attempts and laryngoscopic view, muscle relaxant use is an independent predictor of complications associated with emergency intubation (p = .037), and there is a trend towards improvement of oxygenation (p = .07). Conclusion: The use of neuromuscular blocking agents, when used by intensivists with a high level of training and experience, is associated with a decrease in procedure-related complications. (Crit Care Med 2012; 40:1808-1813) C1 [Wilcox, Susan R.; Bittner, Edward A.; Elmer, Jonathan; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Elmer, Jonathan] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Seigel, Todd A.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Emergency Med, Providence, RI 02903 USA. [Nguyen, Nicole Thuy P.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Dhillon, Anahat] Univ Calif Los Angeles, Dept Anesthesia, Ronald Reagan Med Ctr, Los Angeles, CA USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM swilcox1@partners.org OI Wilcox, Susan/0000-0001-7477-7531 FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA FX This work was funded by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. NR 33 TC 33 Z9 37 U1 0 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 2012 VL 40 IS 6 BP 1808 EP 1813 DI 10.1097/CCM.0b013e31824e0e67 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 946EZ UT WOS:000304335600016 PM 22610185 ER PT J AU Glynn, SM AF Glynn, Shirley M. TI Family Interventions in Schizophrenia: Promise and Pitfalls over 30 Years SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Schizophrenia; Family treatment; Psychosocial interventions; Family therapy; Family interventions; Psychosis; Evidence-based practice; Relatives ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIOR THERAPY; SUBSTANCE USE DISORDERS; SERIOUS MENTAL-ILLNESS; TREATMENT RECOMMENDATIONS; RELATIVES; PROGRAM; EDUCATION; RECOVERY; OUTCOMES AB The stress of living with unpredictable, disturbing schizophrenic symptoms can erode interpersonal relationships. Stressful family interactions are associated with poorer prognosis. Several investigators have developed educational or more intensive skills-based family programs to increase illness knowledge and improve prognosis in schizophrenia. An extensive body of research supports the benefits of participating in family-based treatments for schizophrenia, especially those of longer duration and emphasizing skill development, in reducing relapse rates. In spite of the data, these programs are underimplemented and underutilized. Barriers to their use likely arise from patients, relatives, and mental health professionals. Newer programs, which include novel engagement strategies, target subpopulations with poor prognoses, or use innovative technologies, may make these programs more accessible to a wider range of families. Engaging individuals with schizophrenia and their loved ones in a collaborative effort to design new, more consumer-driven family interventions is warranted. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst W Los Ange, Semel Inst, Los Angeles, CA 90073 USA. RP Glynn, SM (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst W Los Ange, Semel Inst, B151j,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sglynn@ucla.edu NR 49 TC 7 Z9 7 U1 5 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD JUN PY 2012 VL 14 IS 3 BP 237 EP 243 DI 10.1007/s11920-012-0265-z PG 7 WC Psychiatry SC Psychiatry GA 940AL UT WOS:000303862300011 PM 22437626 ER PT J AU Zuleger, CL Albertini, MR AF Zuleger, Cindy L. Albertini, Mark R. TI OMIP-008: Measurement of Th1 and Th2 cytokine polyfunctionality of human T cells SO CYTOMETRY PART A LA English DT Article DE immunophenotype; T cells; intracellular cytokine staining; melanoma C1 [Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI 53705 USA. [Zuleger, Cindy L.; Albertini, Mark R.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Zuleger, Cindy L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Dermatol, Madison, WI USA. [Albertini, Mark R.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. RP Albertini, MR (reprint author), William S Middleton Mem Vet Adm Med Ctr, Med Serv, Room B-5057,2500 Overlook Terrace, Madison, WI 53705 USA. EM mralbert@wisc.edu FU National Cancer Institute [P30 CA014520]; Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs; Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; Steve Leuthold Family; U.S. PHS [T32AR055893]; Tim Eagle Memorial FX Grant sponsor: National Cancer Institute; Grant number: P30 CA014520; Grant sponsors: Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs; Gretchen and Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; Jay Van Sloan Memorial from the Steve Leuthold Family; Tim Eagle Memorial. Grant sponsor: CLZ was supported by a postdoctoral fellowship by U.S. PHS; Grant number: T32AR055893. NR 5 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JUN PY 2012 VL 81A IS 6 BP 450 EP 452 DI 10.1002/cyto.a.22035 PG 3 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 945FO UT WOS:000304258400005 PM 22431369 ER PT J AU Lopes-Virella, MF Baker, NL Hunt, KJ Lyons, TJ Jenkins, AJ Virella, G AF Lopes-Virella, Maria F. Baker, Nathaniel L. Hunt, Kelly J. Lyons, Timothy J. Jenkins, Alicia J. Virella, Gabriel CA DCCT EDIC Study Grp TI High Concentrations of AGE-LDL and Oxidized LDL in Circulating Immune Complexes Are Associated With Progression of Retinopathy in Type 1 Diabetes SO DIABETES CARE LA English DT Article ID INTIMA-MEDIA THICKNESS; COMPLICATIONS TRIAL; ADVANCED GLYCATION; HUMAN MACROPHAGES; MELLITUS; EPIDEMIOLOGY; LIPOPROTEIN; PRODUCTS; CELLS; INFLAMMATION AB OBJECTIVE-To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS-Levels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression. RESULTS-In unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A(1c) (HbA(1c)), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19-1.81]; AGE-LDL-IC) and 45% (1.45 [1.17-1.80]; oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12-1.66]; to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, FIR for progression to PDR was 2.38 (95% CI 1.30-4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03-1.62]). Similar results were observed for oxLDL-ICs. CONCLUSIONS-Increased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression. C1 [Lopes-Virella, Maria F.; Baker, Nathaniel L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.; Hunt, Kelly J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lyons, Timothy J.; Jenkins, Alicia J.] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK USA. [Lyons, Timothy J.; Jenkins, Alicia J.] Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM virellam@musc.edu FU National Institutes of Health(NIH)/National Heart, Lung, and Blood Institute [P01-HL-55782]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-081352, R01-DK-088778]; Juvenile Diabetes Research Foundation [2006-49]; Research Service of the Ralph H. Johnson VA Medical Center; Division of Diabetes, Endocrinology, and Metabolic Diseases (NIDDK) of the NIH; National Center for Research Resources; Genentech Inc.; NIDDK FX This work was supported by a Program Project funded by the National Institutes of Health(NIH)/National Heart, Lung, and Blood Institute (P01-HL-55782), R01 grants funded by NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01-DK-081352 and R01-DK-088778), and by a Juvenile Diabetes Research Foundation grant (2006-49). This work was also supported by the Research Service of the Ralph H. Johnson VA Medical Center. The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology, and Metabolic Diseases (NIDDK) of the NIH. Additional support was provided by the National Center for Research Resources through the General Clinical Research Centers program and by Genentech Inc., through a Cooperative Research and Development Agreement with the NIDDK. No other potential conflicts of interest relevant to this article were reported. NR 41 TC 20 Z9 21 U1 0 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 2012 VL 35 IS 6 BP 1333 EP 1340 DI 10.2337/dc11-2040 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950DY UT WOS:000304631000023 PM 22511260 ER PT J AU de Boer, IH Katz, R Chonchol, MB Fried, LF Ix, JH Kestenbaum, B Mukamal, KJ Peralta, CA Siscovick, DS AF de Boer, Ian H. Katz, Ronit Chonchol, Michel B. Fried, Linda F. Ix, Joachim H. Kestenbaum, Bryan Mukamal, Kenneth J. Peralta, Carmen A. Siscovick, David S. TI Insulin Resistance, Cystatin C, and Mortality Among Older Adults SO DIABETES CARE LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; INCIDENT CARDIOVASCULAR-DISEASE; CHRONIC KIDNEY-DISEASE; METABOLIC SYNDROME; SERUM CREATININE; HEART-DISEASE; RISK; POPULATION; HYPERINSULINEMIA; INDIVIDUALS AB OBJECTIVE-Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes. RESEARCH DESIGN AND METHODS-We performed a cohort study of 3,138 Cardiovascular Health Study participants (age >= 65years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR). RESULTS-A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21% (95% CI 6-41) and 11% (-3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22% (4-43) and 4% (-12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models. CONCLUSIONS-Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship. Diabetes Care 35:1355-1360,2012 C1 [de Boer, Ian H.; Katz, Ronit; Kestenbaum, Bryan; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Chonchol, Michel B.] Univ Colorado, Denver, CO 80202 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ix, Joachim H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Peralta, Carmen A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP de Boer, IH (reprint author), Univ Washington, Seattle, WA 98195 USA. EM deboer@u.washington.edu FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295]; National Institutes of Health [R01-AG-027002, R01-DK-087726]; National Institute of Neurologic Disorders and Stroke FX The research reported in this article was supported by Contracts N0I-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and Grant U01-HL-080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurologic Disorders and Stroke. Additional support came from National Institutes of Health Grants R01-AG-027002 and R01-DK-087726. A full list of principal CHS investigators and 10. institutions can be found at hup://www.chs-nhIbi. org/pi.htm. NR 36 TC 13 Z9 13 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 2012 VL 35 IS 6 BP 1355 EP 1360 DI 10.2337/dcl1-1657 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950DY UT WOS:000304631000026 PM 22432118 ER PT J AU Khalili, H Chan, AT AF Khalili, Hamed Chan, Andrew T. TI Is Diabetes a Risk Factor for Colorectal Cancer? SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID GROWTH-FACTOR-I; BINDING PROTEIN-3; COLON-CARCINOMA; PLASMA-INSULIN; MELLITUS; RECEPTORS; COHORT; P21RAS; TYPE-2; MEN C1 [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-728A, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA137178] NR 30 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2012 VL 57 IS 6 BP 1427 EP 1429 DI 10.1007/s10620-012-2175-7 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 946ZP UT WOS:000304396700001 PM 22531890 ER PT J AU Houser, CR Zhang, NH Peng, ZC Huang, CS Cetina, Y AF Houser, Carolyn R. Zhang, Nianhui Peng, Zechun Huang, Christine S. Cetina, Yliana TI Neuroanatomical clues to altered neuronal activity in epilepsy: From ultrastructure to signaling pathways of dentate granule cells SO EPILEPSIA LA English DT Article DE Electron microscopy; Extracellular signal-regulated kinase; Fos; Mossy fiber sprouting; Seizure; Temporal lobe epilepsy ID TEMPORAL-LOBE EPILEPSY; REGULATED KINASE ACTIVATION; MOSSY FIBER SYNAPSES; PILOCARPINE-INDUCED SEIZURES; KAPPA-OPIOID RECEPTORS; LONG-TERM POTENTIATION; ACID-TREATED RATS; SYNAPTIC REORGANIZATION; HIPPOCAMPAL-FORMATION; FASCIA-DENTATA AB The dynamic aspects of epilepsy, in which seizures occur sporadically and are interspersed with periods of relatively normal brain function, present special challenges for neuroanatomical studies. Although numerous morphologic changes can be identified during the chronic period, the relationship of many of these changes to seizure generation and propagation remains unclear. Mossy fiber sprouting is an example of a frequently observed morphologic change for which a functional role in epilepsy continues to be debated. This review focuses on neuroanatomically identified changes that would support high levels of activity in reorganized mossy fibers and potentially associated granule cell activation. Early ultrastructural studies of reorganized mossy fiber terminals in human temporal lobe epilepsy tissue have identified morphologic substrates for highly efficacious excitatory connections among granule cells. If similar connections in animal models contribute to seizure activity, activation of granule cells would be expected. Increased labeling with two activity-related markers, Fos and phosphorylated extracellular signalregulated kinase, has suggested increased activity of dentate granule cells at the time of spontaneous seizures in a mouse model of epilepsy. However, neuroanatomical support for a direct link between activation of reorganized mossy fiber terminals and increased granule cell activity remains elusive. As novel activity-related markers are developed, it may yet be possible to demonstrate such functional links and allow mapping of seizure activity throughout the brain. Relating patterns of neuronal activity during seizures to the underlying morphologic changes could provide important new insights into the basic mechanisms of epilepsy and seizure generation. C1 [Houser, Carolyn R.; Zhang, Nianhui; Peng, Zechun; Huang, Christine S.; Cetina, Yliana] Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] Vet Adm Greater Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, CHS 73-235,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU Veterans Affairs Medical Research Funds; National Institutes of Health [NS046524, NS051311] FX This work was supported by Veterans Affairs Medical Research Funds (C.R.H.) and the National Institutes of Health grants NS046524 and NS051311 (C.R.H.). We are grateful to Drs. J.R. Rich, P.S. Dwan, B.E. Swartz, G.O. Walsh, and A.V. Delgado-Escueta, and to their patients, for invaluable contributions to our early studies of human temporal lobe epilepsy tissue. This review is contributed as a tribute to H. Jurgen Wenzel in recognition of his careful, detailed morphologic studies, which have been linked consistently to function, and his great interest in mossy fibers of the dentate gyrus, from their early development (Wenzel et al., 1981) to their functionally associated transporters (Wenzel et al., 1997), and to their reorganization in epilepsy (Wenzel et al., 2000). NR 73 TC 15 Z9 15 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2012 VL 53 SU 1 SI SI BP 67 EP 77 DI 10.1111/j.1528-1167.2012.03477.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 945FH UT WOS:000304257700010 PM 22612811 ER PT J AU D'Ascenzo, F Presutti, DG Picardi, E Moretti, C Omede, P Sciuto, F Novara, M Yan, AT Goodman, S Mahajan, N Kosuge, M Palazzuoli, A Jong, GP Isma'eel, H Budoff, MJ Rubinshtein, R Gewirtz, H Reed, MJ Theroux, P Biondi-Zoccai, G Modena, MG Sheiban, I Gaita, F AF D'Ascenzo, Fabrizio Presutti, Davide Giacomo Picardi, Elisa Moretti, Claudio Omede, Pierluigi Sciuto, Filippo Novara, Marco Yan, Andrew T. Goodman, Shaun Mahajan, Nitin Kosuge, Masami Palazzuoli, Alberto Jong, Gwo-Ping Isma'eel, Hussain Budoff, Matthew J. Rubinshtein, Ronen Gewirtz, Henry Reed, Matthew J. Theroux, Pierre Biondi-Zoccai, Giuseppe Modena, Maria Grazia Sheiban, Imad Gaita, Fiorenzo TI Prevalence and non-invasive predictors of left main or three-vessel coronary disease: evidence from a collaborative international meta-analysis including 22 740 patients SO HEART LA English DT Article ID ST-SEGMENT ELEVATION; ACUTE MYOCARDIAL-INFARCTION; TIMI RISK SCORE; ARTERY-DISEASE; LEAD AVR; HEART-FAILURE; 12-LEAD ELECTROCARDIOGRAPHY; ANGIOGRAPHIC FINDINGS; SYSTEMATIC REVIEWS; PROGNOSTIC VALUE AB Background Left main disease (LMD) and three-vessel disease (3VD) have important prognostic value in patients with coronary artery disease. However, uncertainties still exist about their prevalence and predictors in patients with acute coronary syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of this study was to perform an international collaborative systematic review and meta-analysis to appraise the prevalence and predictors of LMD and 3VD. Methods Medline/PubMed were systematically searched for eligible studies published up to 2010, reporting multivariate predictors of LMD or 3VD. Study features, patient characteristics, and prevalence and predictors of LMD and 3VD were abstracted and pooled with random-effect methods (95% CIs). Results 17 studies (22 740 patients) were included, 11 focusing on ACS (17 896 patients) and six on stable coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20% (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95% CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%), with the most powerful predictors being transient ischaemic dilation during the imaging stress test, extent of ST-segment elevation in aVR and V1 during the stress test, and hyperlipidaemia. Conclusions This meta-analysis demonstrated that severe coronary disease-that is, LMD or 3VD-is more common in patients with ACS or stable coronary disease than generally perceived, and that simple and low-cost tools may help in the selection of the most appropriate therapeutic approach. C1 [D'Ascenzo, Fabrizio; Presutti, Davide Giacomo; Picardi, Elisa; Moretti, Claudio; Omede, Pierluigi; Sciuto, Filippo; Novara, Marco; Sheiban, Imad; Gaita, Fiorenzo] Univ Turin, Div Cardiol, I-10126 Turin, Italy. [Yan, Andrew T.; Goodman, Shaun] Maimonides Hosp, Dept Med, Brooklyn, NY 11219 USA. [Mahajan, Nitin] Yokohama City Univ, Med Ctr, Div Cardiol, Yokohama, Kanagawa 232, Japan. [Kosuge, Masami] Univ Siena, Cardiol Sect, Dept Internal Med & Metab Dis, I-53100 Siena, Italy. [Palazzuoli, Alberto] Natl Yang Ming Univ, Inst Publ Hlth, Community Med Res Ctr, Yang Ming, Peoples R China. [Jong, Gwo-Ping] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. [Isma'eel, Hussain; Budoff, Matthew J.] Technion IIT, Ruth & Bruce Rappaport Sch Med, Haifa, Israel. [Isma'eel, Hussain; Budoff, Matthew J.] Technion IIT, Lady Davis Carmel Med Ctr, Dept Cardiovasc Med, Haifa, Israel. [Rubinshtein, Ronen] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gewirtz, Henry] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Gewirtz, Henry] Canadian Heart Res Ctr, Toronto, ON, Canada. [Reed, Matthew J.; Biondi-Zoccai, Giuseppe; Modena, Maria Grazia] Univ Modena & Reggio Emilia, Div Cardiol, Modena, Italy. [D'Ascenzo, Fabrizio; Moretti, Claudio; Theroux, Pierre; Biondi-Zoccai, Giuseppe] Meta Anal & Evidence Based Med Training Cardiol M, Ospedaletti, Italy. RP D'Ascenzo, F (reprint author), Univ Turin, Div Cardiol, S Giovanni Battista Molinette Hosp, Corso Bramante 88-90, I-10126 Turin, Italy. EM fabrizio.dascenzo@gmail.com RI MORETTI, CLAUDIO/G-4396-2012; modena, maria grazia/N-2442-2015; OI modena, maria grazia/0000-0002-4704-4663; MORETTI, CLAUDIO/0000-0002-4475-7289; Reed, Matthew/0000-0003-1308-4824 NR 57 TC 26 Z9 28 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JUN PY 2012 VL 98 IS 12 BP 914 EP 919 DI 10.1136/heartjnl-2011-301596 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 947FM UT WOS:000304414000005 PM 22626899 ER PT J AU Kim, H Miller, LM Byl, N Abrams, GM Rosen, J AF Kim, Hyunchul Miller, Levi Makaio Byl, Nancy Abrams, Gary M. Rosen, Jacob TI Redundancy Resolution of the Human Arm and an Upper Limb Exoskeleton SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Exoskeleton; inverse kinematic; redundancy; swivel angle ID POWERED EXOSKELETON; INVERSE KINEMATICS; COMPLEX MOVEMENTS; MICROSTIMULATION; CONFIGURATION; CORTEX AB The human arm has 7 degrees of freedom (DOF) while only 6 DOF are required to position the wrist and orient the palm. Thus, the inverse kinematics of an human arm has a nonunique solution. Resolving this redundancy becomes critical as the human interacts with a wearable robot and the inverse kinematics solution of these two coupled systems must be identical to guarantee an seamless integration. The redundancy of the arm can be formulated by defining the swivel angle, the rotation angle of the plane defined by the upper and lower arm around a virtual axis that connects the shoulder and wrist joints. Analyzing reaching tasks recorded with a motion capture system indicates that the swivel angle is selected such that when the elbow joint is flexed, the palm points to the head. Based on these experimental results, a new criterion is formed to resolve the human arm redundancy. This criterion was implemented into the control algorithm of an upper limb 7-DOF wearable robot. Experimental results indicate that by using the proposed redundancy resolution criterion, the error between the predicted and the actual swivel angle adopted by the motor control system is less then 5 degrees. C1 [Kim, Hyunchul] Univ Calif Santa Cruz, Dept Elect Engn, Santa Cruz, CA 95064 USA. [Kim, Hyunchul] Optodynamics Inc, Songnam 463870, South Korea. [Miller, Levi Makaio] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Miller, Levi Makaio] Carbon Design Grp, Seattle, WA 98105 USA. [Byl, Nancy] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, Sch Med, San Francisco, CA 94158 USA. [Abrams, Gary M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Abrams, Gary M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Rosen, Jacob] Univ Calif Santa Cruz, Dept Comp Engn, Santa Cruz, CA 95064 USA. [Rosen, Jacob] Univ Calif Santa Cruz, Bion Lab, Santa Cruz, CA 95064 USA. RP Kim, H (reprint author), Atromax Inc, Santa Clara, CA USA. EM hyunchul78@gmail.com; makaio@uw.edu; BylN@ptrehab.ucsf.edu; Gary.Abrams@ucsf.edu; rosen@ucsc.edu NR 26 TC 26 Z9 26 U1 2 U2 33 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2012 VL 59 IS 6 BP 1770 EP 1779 DI 10.1109/TBME.2012.2194489 PG 10 WC Engineering, Biomedical SC Engineering GA 944ZQ UT WOS:000304242700029 PM 22510944 ER PT J AU Luo, G Peli, E AF Luo, Gang Peli, Eli TI Methods for Automated Identification of Informative Behaviors in Natural Bioptic Driving SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Bioptic driving; driving behavior; instrumented vehicle; natural driving study ID TELESCOPIC SPECTACLE; OLDER DRIVERS; MOTOR-VEHICLE; ACCIDENTS; HAZARD AB Visually impaired people may legally drive if wearing bioptic telescopes in some developed countries. To address the controversial safety issue of the practice, we have developed a low-cost in-car recording system that can be installed in study participants' own vehicles to record their daily driving activities. We also developed a set of automated identification techniques of informative behaviors to facilitate efficient manual review of important segments submerged in the vast amount of uncontrolled data. Here, we present the methods and quantitative results of the detection performance for six types of driving maneuvers and behaviors that are important for bioptic driving: bioptic telescope use, turns, curves, intersections, weaving, and rapid stops. The testing data were collected from one normally sighted and two visually impaired subjects across multiple days. The detection rates ranged from 82% up to 100%, and the false discovery rates ranged from 0% to 13%. In addition, two human observers were able to interpret about 80% of targets viewed through the telescope. These results indicate that with appropriate data processing the low-cost system is able to provide reliable data for natural bioptic driving studies. C1 [Luo, Gang; Peli, Eli] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Luo, Gang; Peli, Eli] Harvard Univ, Dept Ophthalmol, Sch Med, Cambridge, MA 02138 USA. RP Luo, G (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. EM gang.luo@schepens.harvard.edu; eli.peli@schepens.harvard.edu FU National Institute of Health [AG034553, EY12890] FX This work was supported in part by the National Institute of Health under Grant AG034553 (GL) and Grant EY12890 (EP). NR 27 TC 0 Z9 0 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2012 VL 59 IS 6 BP 1780 EP 1786 DI 10.1109/TBME.2012.2191406 PG 7 WC Engineering, Biomedical SC Engineering GA 944ZQ UT WOS:000304242700030 PM 22514200 ER PT J AU Lambert, A Picardeau, M Haake, DA Sermswan, RW Srikram, A Adler, B Murray, GA AF Lambert, Ambroise Picardeau, Mathieu Haake, David A. Sermswan, Rasana W. Srikram, Amporn Adler, Ben Murray, Gerald A. TI FlaA Proteins in Leptospira interrogans Are Essential for Motility and Virulence but Are Not Required for Formation of the Flagellum Sheath SO INFECTION AND IMMUNITY LA English DT Article ID BORRELIA-BURGDORFERI; PERIPLASMIC FLAGELLA; INACTIVATION; MUTAGENESIS; GENE; INVOLVEMENT; CHEMOTAXIS; TRANSPOSON; MUTANT AB Spirochetes have periplasmic flagella composed of a core surrounded by a sheath. The pathogen Leptospira interrogans has four flaB (proposed core subunit) and two flaA (proposed sheath subunit) genes. The flaA genes are organized in a locus with flaA2 immediately upstream of flaA1. In this study, flaA1 and flaA2 mutants were constructed by transposon mutagenesis. Both mutants still produced periplasmic flagella. The flaA 1 mutant did not produce FlaA1 but continued to produce FlaA2 and retained normal morphology and virulence in a hamster model of infection but had reduced motility. The flaA2 mutant did not produce either the FlaA1 or the FlaA2 protein. Cells of the flaA2 mutant lacked the distinctive hook-shaped ends associated with L. interrogans and lacked translational motility in liquid and semisolid media. These observations were confirmed with a second, independent flaA2 mutant. The flaA2 mutant failed to cause disease in animal models of acute infection. Despite lacking FlaA proteins, the flagella of the flaA2 mutant were of the same thickness as wild-type flagella, as measured by electron microscopy, and exhibited a normal flagellum sheath, indicating that FlaA proteins are not essential for the synthesis of the flagellum sheath, as observed for other spirochetes. This study shows that FlaA subunits contribute to leptospiral translational motility, cellular shape, and virulence. C1 [Adler, Ben; Murray, Gerald A.] Monash Univ, Dept Microbiol, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic 3168, Australia. [Sermswan, Rasana W.; Srikram, Amporn] Khon Kaen Univ, Melioidosis Res Ctr, Khon Kaen, Thailand. [Sermswan, Rasana W.] Khon Kaen Univ, Dept Biochem, Khon Kaen, Thailand. [Haake, David A.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lambert, Ambroise] Univ Paris Diderot, Paris, France. [Lambert, Ambroise; Picardeau, Mathieu] Inst Pasteur, Unite Biol Spirochetes, Paris, France. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic 3168, Australia. EM ben.adler@monash.edu FU Australian Research Council; National Health and Medical Research Council; Institut Pasteur; French Ministry of Research [ANR-08-MIE-018]; University Paris Diderot; VA Medical Research funds; Public Health Service from the National Institute of Allergy and Infectious Diseases [AI-034431] FX This work was supported by the Australian Research Council, the National Health and Medical Research Council, the Institut Pasteur, the French Ministry of Research (ANR-08-MIE-018), the doctoral program of the University Paris Diderot, VA Medical Research funds, and Public Health Service grant AI-034431 from the National Institute of Allergy and Infectious Diseases. NR 33 TC 44 Z9 44 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2012 VL 80 IS 6 BP 2019 EP 2025 DI 10.1128/IAI.00131-12 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 946WH UT WOS:000304387700008 PM 22451522 ER PT J AU Hoeppner, BB Redding, CA Rossi, JS Pallonen, UE Prochaska, JO Velicer, WF AF Hoeppner, Bettina B. Redding, Colleen A. Rossi, Joseph S. Pallonen, Unto E. Prochaska, James O. Velicer, Wayne F. TI Factor Structure of Decisional Balance and Temptations Scales for Smoking: Cross-Validation in Urban Female African-American Adolescents SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Transtheoretical model; Decisional Balance; Temptations; Smoking; African-Americans; Adolescents ID 12 PROBLEM BEHAVIORS; HEALTH BEHAVIORS; SELF-EFFICACY; TRANSTHEORETICAL MODEL; WEAK PRINCIPLES; FIT INDEXES; CESSATION; PRECONTEMPLATION; ASSOCIATION; DISPARITIES AB Background The transtheoretical model is an influential theoretical model in health psychology, particularly in its application to smoking cessation research. Decisional Balance (DB) and Temptations are key constructs within this framework. Purpose This study examines the psychometric properties of the DB and Temptations scales for smoking in a predominantly African-American sample of urban adolescent girls. Methods We used confirmatory factor analysis to compare the fit of previously published factor structures in smokers (n=233) and nonsmokers (n=598). External validity was tested by examining stages of change differences in the retained subscales. Results Results supported the internal and external validity of the DB scale for smokers and nonsmokers. Notably, previously published three-factor (Social Pros, Coping Pros, Cons) and four-factor (Cons split into "Aesthetic Cons" and "Health Cons") models fit equally well, with Cons subscales correlating highly. For Temptations, a previously published three-factor (Negative Affect, Social, Weight Control) hierarchical model fit well in nonsmokers. In smokers, previously published subscales were reliably measured, but their structural relationship remained unclear. Stage difference tests showed medium to large effect sizes of DB and Temptation subscales in smokers and nonsmokers. Conclusions The use of DB was validated for both smokers and nonsmokers in this sample of primarily African-American adolescent females, where Cons can be combined or separated into "Aesthetic Cons" and "Health Cons" based on practical utility and preference. For Temptations, more research is needed but large stage differences in Temptations subscales underscore the importance of this concept in smoking acquisition and cessation. C1 [Hoeppner, Bettina B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA 02114 USA. [Hoeppner, Bettina B.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Redding, Colleen A.; Rossi, Joseph S.; Prochaska, James O.; Velicer, Wayne F.] Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. [Pallonen, Unto E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX USA. RP Hoeppner, BB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM bhoeppner@partners.org; credding@uri.edu RI Redding, Colleen /J-8261-2012 OI Redding, Colleen /0000-0002-5044-3155 FU NCI NIH HHS [CA50087, CA63045, P01 CA050087]; NIAAA NIH HHS [T32 AA007459, T32 AA007459-21]; NIDA NIH HHS [L30 DA025511, L30 DA025511-02, R01 DA023191] NR 45 TC 4 Z9 4 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD JUN PY 2012 VL 19 IS 2 BP 217 EP 227 DI 10.1007/s12529-011-9145-x PG 11 WC Psychology, Clinical SC Psychology GA 947AR UT WOS:000304399500010 PM 21279493 ER PT J AU Mukherjee, A Larson, EA Carlos, AS Belknap, JK Rotwein, P Klein, RF AF Mukherjee, Aditi Larson, Emily A. Carlos, Amy S. Belknap, John K. Rotwein, Peter Klein, Robert F. TI Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor beta 1-mediated signaling and bone acquisition SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE HEREDITY; GENETICS; TRANSFORMING GROWTH FACTOR; BONE STRENGTH; OSTEOPOROSIS ID QUANTITATIVE TRAIT LOCI; INHIBITS OSTEOBLAST DIFFERENTIATION; TGF-BETA ACTIVATION; MINERAL DENSITY; MECHANICAL-PROPERTIES; PARATHYROID-HORMONE; COMPLEX TRAITS; OSTEOPOROSIS; MOUSE; IDENTIFICATION AB Osteoporosis, the most common skeletal disorder, is characterized by low bone mineral density (BMD) and an increased risk of fragility fractures. BMD is the best clinical predictor of future osteoporotic fracture risk, but is a complex trait controlled by multiple environmental and genetic determinants with individually modest effects. Quantitative trait locus (QTL) mapping is a powerful method for identifying chromosomal regions encompassing genes involved in shaping complex phenotypes, such as BMD. Here we have applied QTL analysis to male and female genetically-heterogeneous F2 mice derived from a cross between C57BL/6 and DBA/2 strains, and have identified 11 loci contributing to femoral BMD. Further analysis of a QTL on mouse chromosome 7 following the generation of reciprocal congenic strains has allowed us to determine that the high BMD trait, which tracks with the DBA/2 chromosome and exerts equivalent effects on male and female mice, is manifested by enhanced osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and by increased growth of metatarsal bones in short-term primary culture. An insertion/deletion DNA polymorphism in Ltbp4 exon 12 that causes the in-frame removal of 12 codons in the DBA/2-derived gene maps within 0.6?Mb of the marker most tightly linked to the QTL. LTBP4, one of four paralogous mouse proteins that modify the bioavailability of the transforming growth factor beta (TGF-beta) family of growth factors, is expressed in differentiating MSC-derived osteoblasts and in long bones, and reduced responsiveness to TGF-beta 1 is observed in MSCs of mice homozygous for the DBA/2 chromosome 7. Taken together, our results identify a potential genetic and biochemical relationship between decreased TGF-beta 1mediated signaling and enhanced femoral BMD that may be regulated by a variant LTBP4 molecule. (C) 2012 American Society for Bone and Mineral Research. C1 [Larson, Emily A.; Carlos, Amy S.; Klein, Robert F.] Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Dept Med, Portland, OR 97201 USA. [Mukherjee, Aditi; Rotwein, Peter] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. [Belknap, John K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Belknap, John K.; Klein, Robert F.] Portland VA Med Ctr, Portland, OR USA. RP Klein, RF (reprint author), Oregon Hlth & Sci Univ, Bone & Mineral Res Unit CR113, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM kleinro@ohsu.edu FU National Institutes of Health [R01 DK42748, P50 AA10760, R01 AR44659]; VA Medical Research Service FX These studies were supported in part by National Institutes of Health grants R01 DK42748 (to PR), P50 AA10760 (to JKB), R01 AR44659 (to RFK), and the VA Medical Research Service (to RFK). We thank Dr. Lynn Sakai for polyclonal antibodies to LTBP4. NR 59 TC 8 Z9 8 U1 0 U2 3 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 2012 VL 27 IS 6 BP 1345 EP 1356 DI 10.1002/jbmr.1590 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943QY UT WOS:000304141500012 PM 22407846 ER PT J AU Heckman, CJ Cohen-Filipic, J AF Heckman, Carolyn J. Cohen-Filipic, Jessye TI Brief Report: Ultraviolet Radiation Exposure, Considering Acculturation Among Hispanics (Project URECAH) SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Hispanics; Skin cancer; Prevention; Acculturation ID SUN PROTECTION PRACTICES; BEHAVIORS AB Very few studies have examined acculturation of Hispanics as it relates to skin cancer prevention attitudes and behaviors. This pilot study used the Abbreviated Acculturation Rating Scale for Mexican Americans-II to classify 14-25-year-old Hispanics as traditional, bicultural, or acculturated. More acculturated individuals reported significantly higher perceived benefits of ultraviolet radiation exposure and lower worry about skin damage than traditional individuals. Bicultural individuals reported using sunscreen significantly more often than acculturated individuals. These preliminary data suggest that more acculturated Hispanic young adults may demonstrate riskier skin cancer-related attitudes and behaviors than others. C1 [Heckman, Carolyn J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cohen-Filipic, Jessye] Portland VA Med Ctr, Portland, OR 97239 USA. RP Heckman, CJ (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Carolyn.Heckman@fccc.edu; JessyeCohen@gmail.com FU NCI NIH HHS [K07 CA108685, K07 CA108685-05] NR 15 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD JUN PY 2012 VL 27 IS 2 BP 342 EP 346 DI 10.1007/s13187-011-0308-x PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 943SC UT WOS:000304144500021 PM 22228464 ER PT J AU Safren, SA O'Cleirigh, CM Bullis, JR Otto, MW Stein, MD Pollack, MH AF Safren, Steven A. O'Cleirigh, Conall M. Bullis, Jacqueline R. Otto, Michael W. Stein, Michael D. Pollack, Mark H. TI Cognitive Behavioral Therapy for Adherence and Depression (CBT-AD) in HIV-Infected Injection Drug Users: A Randomized Controlled Trial SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE HIV/AIDS; antiretroviral therapy (ART); depression; adherence; substance abuse ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL LOAD; MEDICATION ADHERENCE; VIROLOGICAL RESPONSE; PSYCHOSOCIAL FACTORS; DISEASE PROGRESSION; INCREASE ADHERENCE; INHIBITOR THERAPY; METAANALYSIS AB Objective: Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment adherence. Injection drug users comprise a substantial portion of individuals with HIV in the United States and globally. The present study tested cognitive behavioral therapy for adherence and depression (CBT-AD) in patients with HIV and depression in active substance abuse treatment for injection drug use. Method: This is a 2-arm, randomized controlled trial (N = 89) comparing CBT-AD with enhanced treatment as usual (ETAU). Analyses were conducted for two time-frames: (a) baseline to post-treatment and (b) post-treatment to follow-up at 3 and 6 months after intervention discontinuation. Results: At post-treatment, the CBT-AD condition showed significantly greater improvement than ETAU in MEMS (electronic pill cap) based adherence, gamma(slope) = 0.8873, t(86) = 2.38, p = .02; d(GMA-raw), = 0.64, and depression, assessed by blinded assessor: Mongomery-Asberg Depression Rating Scale, F(1, 79) = 6.52, p < .01, d = 0.55; clinical global impression, F(1, 79) = 14.77, p < .001, d = 0.85. After treatment discontinuation, depression gains were maintained, but adherence gains were not. Viral load did not differ across condition; however, the CBT-AD condition had significant improvements in CD4 cell counts over time compared with ETAU, gamma(slope) = 2.09, t(76) = 2.20,p = .03, d(GMA-raw) = 0.60. Conclusions: In patients managing multiple challenges including HIV, depression, substance dependence, and adherence, CBT-AD is a useful way to integrate treatment of depression with an adherence intervention. Continued adherence counseling is likely needed, however, to maintain or augment adherence gains in this population. C1 [Safren, Steven A.; O'Cleirigh, Conall M.; Pollack, Mark H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Safren, Steven A.; O'Cleirigh, Conall M.; Bullis, Jacqueline R.; Pollack, Mark H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bullis, Jacqueline R.; Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Stein, Michael D.] Butler Hosp, Providence, RI 02906 USA. [Stein, Michael D.] Brown Univ, Providence, RI 02912 USA. RP Safren, SA (reprint author), MGH Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssafren@partners.org FU NIDA NIH HHS [R01 DA018603, R01 DA018603-01, R01DA018603] NR 55 TC 60 Z9 61 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 2012 VL 80 IS 3 BP 404 EP 415 DI 10.1037/a0028208 PG 12 WC Psychology, Clinical SC Psychology GA 948MT UT WOS:000304508000009 PM 22545737 ER PT J AU Ghosh, PM Shu, ZJ Zhu, B Lu, ZD Ikeno, YJ Barnes, JL Yeh, CK Zhang, BX Katz, MS Kamat, A AF Ghosh, Paramita M. Shu, Zhen-Ju Zhu, Bing Lu, Zhongding Ikeno, Yuji Barnes, Jeffrey L. Yeh, Chih-Ko Zhang, Bin-Xian Katz, Michael S. Kamat, Amrita TI Role of beta-adrenergic receptors in regulation of hepatic fat accumulation during aging SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ISOLATED RAT HEPATOCYTES; LIVER-DISEASE; MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; ADENYLATE-CYCLASE; FISCHER-344 RATS; ADIPOSE-TISSUE; AGE; EXPRESSION; ADRENOCEPTOR AB Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that beta-adrenergic receptor (beta-AR) levels and beta-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Herewe investigated whether age-associated increases in beta-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the beta-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of b1-and b2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of beta-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the beta-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenolmediated hepatic fat accumulation; thus beta-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic beta-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for beta-adrenergic blockers in preventing or retarding the development of hepatic steatosis. Journal of Endocrinology (2012) 213, 251-261 C1 [Ghosh, Paramita M.; Yeh, Chih-Ko; Zhang, Bin-Xian; Katz, Michael S.; Kamat, Amrita] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78229 USA. [Shu, Zhen-Ju; Barnes, Jeffrey L.; Zhang, Bin-Xian; Katz, Michael S.; Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Zhu, Bing; Lu, Zhongding; Yeh, Chih-Ko; Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ikeno, Yuji; Yeh, Chih-Ko; Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Kamat, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM kamat@uthscsa.edu FU Department of Veterans Affairs VISN 17; American Heart Association; Kronos Longevity Research Institute FX Grant sponsor: Department of Veterans Affairs VISN 17 award to A K; grant sponsor: American Heart Association grant in aid to A K; and grant sponsor: Kronos Longevity Research Institute award to M S K. NR 53 TC 14 Z9 14 U1 1 U2 5 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUN PY 2012 VL 213 IS 3 BP 251 EP 261 DI 10.1530/JOE-11-0406 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 946PZ UT WOS:000304366600006 PM 22457517 ER PT J AU Shiner, B D'Avolio, LW Nguyen, TM Zayed, MH Watts, BV Fiore, L AF Shiner, Brian D'Avolio, Leonard W. Nguyen, Thien M. Zayed, Maha H. Watts, Bradley V. Fiore, Louis TI Automated classification of psychotherapy note text: implications for quality assessment in PTSD care SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE health care quality; access; and evaluation; natural language processing; psychotherapy; quality assurance; health care; quality of health care; stress disorders; post-traumatic ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; VETERANS; CLINICS C1 [Shiner, Brian; Zayed, Maha H.; Watts, Bradley V.] VA Med Ctr, White River Jct, VT 05009 USA. [Shiner, Brian; Watts, Bradley V.] VA New England Healthcare Engn Partnership, White River Jct, VT USA. [Shiner, Brian; Watts, Bradley V.] Dartmouth Med Sch, Hanover, NH USA. [D'Avolio, Leonard W.; Nguyen, Thien M.; Fiore, Louis] VA Boston Healthcare Syst, Boston, MA USA. [D'Avolio, Leonard W.; Nguyen, Thien M.; Fiore, Louis] Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [D'Avolio, Leonard W.] Ctr Surg & Publ Hlth, Boston, MA USA. [D'Avolio, Leonard W.] Harvard Univ, Sch Med, Boston, MA USA. [Fiore, Louis] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Shiner, B (reprint author), VA Med Ctr, 215 N Main St 11Q, White River Jct, VT 05009 USA. EM brian.shiner@va.gov FU Veterans Administration; Health Services Research & Development through the Consortium for Healthcare Informatics Research (CHIR) FX Dr Shiner's time is supported by the VA-New England Early Career Development Award Program. This work is made possible by funding from the Veterans Administration Cooperative Studies Program (CSP) and Health Services Research & Development through the Consortium for Healthcare Informatics Research (CHIR). NR 13 TC 10 Z9 10 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD JUN PY 2012 VL 18 IS 3 BP 698 EP 701 DI 10.1111/j.1365-2753.2011.01634.x PG 4 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 939KA UT WOS:000303807600031 PM 21668796 ER PT J AU Suh, JY Cho, G Song, Y Lee, CK Kang, JS Kang, MR Park, SB Kim, YR Kim, JK AF Suh, Ji-Yeon Cho, Gyunggoo Song, Youngkyu Lee, Chang Kyung Kang, Jong Soon Kang, Moo Rim Park, Sung Bin Kim, Young Ro Kim, Jeong Kon TI Is apparent diffusion coefficient reliable and accurate for monitoring effects of antiangiogenic treatment in a longitudinal study? SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE outcome; treatment; diffusion magnetic resonance imaging; inhibitors; angiogenesis ID TUMOR XENOGRAFTS; EARLY THERAPY; LYMPH-NODES; FEASIBILITY; CANCER; EXPERIENCE; PERFUSION; ANTIBODY; SU11248; MRI AB Purpose: To evaluate the reliability and accuracy of the apparent diffusion coefficient (ADC) for monitoring antiangiogenic treatment in a longitudinal study. Materials and Methods: Tumor volume and ADC were monitored by T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted MRI, respectively, in 18 mice with angiogenesis-dependent tumors (U118MG) before (day 0) and after 2, 7, 14, and 21 days of administration of the antiangiogenic agent sunitinib maleate (n = 12) or vehicle (n = 6). Percent changes in tumor volume and ADC were calculated and correlations between tumor volume and ADC were evaluated. Results: Tumor volume and ADC showed a negative correlation at 69 of the 72 (96%) follow-up measurements. In the 13 mice with tumor regrowth, ADC started to decrease before (27%) or at the same time (73%) as tumor regrowth. Pretreatment ADC and percent change in ADC change on days 02 were similar in mice with positive and negative responses to treatment (0.851 vs. 0.999, 24% vs. 16%). Percent change of ADC showed significant negative correlation with percent change in tumor volume in both the control (r = -0.69) and treated (r = -0.65) groups. Conclusion: Percent change in ADC is a reliable and accurate marker for monitoring the effects of antiangiogenic treatment, whereas pretreatment ADC and early changes in ADC (ie, days 02) are limited in predicting treatment outcome. J. Magn. Reson. Imaging 2012;. (c) 2012 Wiley Periodicals, Inc. C1 [Suh, Ji-Yeon; Lee, Chang Kyung; Kim, Jeong Kon] Univ Ulsan, Coll Med, Dept Radiol, Res Inst Radiol,Asan Med Ctr, Seoul 138736, South Korea. [Suh, Ji-Yeon; Cho, Gyunggoo; Song, Youngkyu] Korea Basic Sci Inst, Div Magnet Resonance, Cheongwon, Chungbuk, South Korea. [Kang, Jong Soon; Kang, Moo Rim] Korea Res Inst Biosci & Biotechnol, Cheongwon, Chungbuk, South Korea. [Park, Sung Bin] Cheil Gen Hosp, Dept Radiol, Seoul, South Korea. [Park, Sung Bin] Kwandong Univ, Coll Med, Womens Healthcare Ctr, Seoul, South Korea. [Kim, Young Ro] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Kim, JK (reprint author), Univ Ulsan, Coll Med, Dept Radiol, Res Inst Radiol,Asan Med Ctr, 388-1 Poongnap Dong, Seoul 138736, South Korea. EM kim.jeongkon@gmail.com FU National Research Foundation of Korea (NRF); Ministry of Education, Science of Technology [2011-0005480, 2010-0025731]; Ministry for Health, Welfare Family Affairs [A090754] FX Contract grant sponsor: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science of Technology; Contract grant number: 2011-0005480, 2010-0025731; Contract grant sponsor: Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs; Contract grant number: A090754. NR 26 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2012 VL 35 IS 6 BP 1430 EP 1436 DI 10.1002/jmri.23574 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 942HP UT WOS:000304035100021 PM 22314928 ER PT J AU Adams, JM Potempa, K AF Adams, Jeffrey M. Potempa, Kathleen TI Influencing Nursing Education, Policy, Practice, and Research An Interview With Kathleen Potempa SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 [Adams, Jeffrey M.] Yvonne L Munn Ctr Nursing Res, Boston, MA USA. [Adams, Jeffrey M.] Ctr Innovat Patient Care, Boston, MA USA. [Potempa, Kathleen] AACN, Aliso Viejo, CA USA. [Potempa, Kathleen] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM jadams9@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 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 2012 VL 42 IS 6 BP 318 EP 320 PG 3 WC Nursing SC Nursing GA 947MV UT WOS:000304435000006 ER PT J AU Foreyt, J Kleinman, R Brown, RJ Lindstrom, R AF Foreyt, John Kleinman, Ronald Brown, Rebecca J. Lindstrom, Rachel TI The Use of Low-Calorie Sweeteners by Children: Implications for Weight Management SO JOURNAL OF NUTRITION LA English DT Article ID FOOD-INTAKE; BEVERAGE CONSUMPTION; ENERGY-INTAKE; TASTE RECEPTORS; CHILDHOOD OBESITY; SELF-REGULATION; UNITED-STATES; BODY-WEIGHT; ARTIFICIAL SWEETENERS; INTENSE SWEETENERS AB The rise in pediatric obesity since the 1970s has been well established in the United States and is becoming a major concern worldwide. As a potential means to help slow the obesity epidemic, low-calorie sweeteners (LCS) have gained attention as dietary tools to assist in adherence to weight loss plans or prevention of excess weight gain. Observational studies tend to show positive correlations between LCS consumption and weight gain in children and adolescents. Although the data are intriguing, these epidemiologic studies do not establish that LCS cause weight gain, because there are likely many lifestyle and genetic differences between children and families who choose to consume LCS and those who do not. Short-term randomized controlled trials have shown LCS use to be BMI neutral or to have modest weight-reducing effects in overweight and obese adolescents. The long-term effects of LCS in children and adolescents are unknown. Some compelling research is currently underway and may provide needed insight into the potential role of LCS in weight management. The paucity of data regarding the effects of LCS use in children and adolescents creates challenges in decision-making for health care providers and parents. J. Nutr. 142: 1155S-1162S, 2012. C1 [Foreyt, John] Baylor Coll Med, Houston, TX 77030 USA. [Kleinman, Ronald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Children, Boston, MA USA. [Brown, Rebecca J.] NIH, Bethesda, MD 20892 USA. [Lindstrom, Rachel] Amer Move Fdn, Aurora, CO USA. RP Foreyt, J (reprint author), Baylor Coll Med, Houston, TX 77030 USA. EM jforeyt@bcm.edu FU Kellogg Company; Committee on Low-Calorie Sweeteners of the North American Branch of the International Life Sciences Institute; National Institute of Diabetes, Digestive, and Kidney Diseases FX Published in a supplement to The Journal of Nutrition. Presented at the conference Low-Calorie Sweeteners, Appetite and Weight Control: What the Science Tells Us, held in Washington, DC, April 7-8, 2011. The conference was sponsored by the Committee on Low-calorie Sweeteners of the International Life Sciences Institute North America. The views expressed in these papers are not necessarily those of the supplement coordinator or guest editors. The supplement coordinator for this supplement was Adam Drewnowski, University of Washington. Supplement Coordinator disclosures: Adam Drewnowski received travel reimbursement for participation in the Low-Calorie Sweeteners Conference. The supplement is the responsibility of the Guest Editor to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The Guest Editor for this supplement was Sibylle Kranz. Guest Editor disclosure: Sibylle Kranz has received funding from The Kellogg Company to conduct research projects unrelated to this supplement material. She has also been an invited speaker at a roundtable discussion funded by The Kellogg Company. Publication costs for this supplement were defrayed in part by the payment of page charges. This publication must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition.; Supported by the Committee on Low-Calorie Sweeteners of the North American Branch of the International Life Sciences Institute. J. Foreyt, R. Kleinman, and R. Lindstrom received a modest honorarium for their participation in the workshop and development of the manuscript, as well as travel funding to attend the workshop.; Author disclosures: R. Kleinman has served on an advisory committee for Ajinomoto. J. Foreyt has received consulting fees, honoraria, and unrestricted grants from food, beverage, and pharmaceutical companies and from government and nonprofit sources. R. J. Brown's research was supported in part by the Intramural Research Program of the National Institute of Diabetes, Digestive, and Kidney Diseases. R. Lindstrom, no conflicts of interest. NR 64 TC 10 Z9 10 U1 10 U2 56 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUN PY 2012 VL 142 IS 6 BP 1155S EP 1162S DI 10.3945/jn.111.149609 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 946EY UT WOS:000304335500028 PM 22573780 ER PT J AU Rhodes, ET Goran, MI Lieu, TA Lustig, RH Prosser, LA Songer, TJ Weigensberg, MJ Weinstock, RS Gonzalez, T Rawluk, K Zoghbi, RM Ludwig, DS Laffel, LM AF Rhodes, Erinn T. Goran, Michael I. Lieu, Tracy A. Lustig, Robert H. Prosser, Lisa A. Songer, Thomas J. Weigensberg, Marc J. Weinstock, Ruth S. Gonzalez, Tessa Rawluk, Kaitlin Zoghbi, Roula M. Ludwig, David S. Laffel, Lori M. TI Health-Related Quality of Life in Adolescents with or at Risk for Type 2 Diabetes Mellitus SO JOURNAL OF PEDIATRICS LA English DT Article ID GLYCEMIC CONTROL; CARDIOVASCULAR-DISEASE; FAMILY CONFLICT; OBESE CHILDREN; YOUTH; OVERWEIGHT; PREFERENCES; PREVALENCE; IMPACT; CHALLENGES AB Objective To evaluate how adolescents with or at risk for type 2 diabetes mellitus (T2DM) and their parent/guardians (parents) perceive adolescents' health-related quality of life. Study design We interviewed overweight/obese, 12- to 18-year-old youth with T2DM, prediabetes, or insulin resistance and one parent from 5 US sites. Assessments included Pediatric Quality of Life Inventory (PedsQL), Health Utilities Index, family conflict, and diabetes burden. Results In 108 adolescents, diagnoses included 40.7% with T2DM, 25.0% with prediabetes, and 34.3% with insulin resistance. PedsQL summary score (SS) was higher in adolescents than parents (P = .02). Parents rated physical functioning lower than adolescents (P < .0001), but there were no differences in psychosocial health. Adolescent PedsQL SS did not differ with diagnosis, but was inversely associated with adolescent body mass index z-score (P = .0004) and family conflict (P < .0001) and associated with race/ethnicity (P < .0001). Number of adolescent co-morbidities (P = .007) and burden of diabetes care (P < .05) were inversely associated with parent PedsQL SS. There were no differences in the Health Utilities Index-Mark 3 multi-attribute utility score. Conclusions Parents perceive their adolescents' physical functioning as more impaired than adolescents themselves. Contextual factors including severity of obesity, race/ethnicity, family conflict, and burden of diabetes care influence health-related quality of life. Family-based approaches to treatment and prevention of T2DM may benefit from increased attention to the biopsychosocial context. (J Pediatr 2011;square:square-square). C1 [Rhodes, Erinn T.; Ludwig, David S.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Lieu, Tracy A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Rhodes, Erinn T.; Lieu, Tracy A.; Ludwig, David S.; Laffel, Lori M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Goran, Michael I.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Goran, Michael I.; Weigensberg, Marc J.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Lieu, Tracy A.; Prosser, Lisa A.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Child Hlth Care Studies, Boston, MA USA. [Lustig, Robert H.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Prosser, Lisa A.] Univ Michigan, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. [Songer, Thomas J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. [Gonzalez, Tessa] Palmetto Hlth Childrens Hosp, Dept Pediat, Columbia, SC USA. [Rawluk, Kaitlin] Duke Univ, Sch Med, Durham, NC USA. [Zoghbi, Roula M.] Texas Childrens Hosp, Houston, TX 77030 USA. [Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Rhodes, ET (reprint author), Childrens Hosp, Div Endocrinol, 300 Longwood Ave,6th Floor, Boston, MA 02115 USA. EM Erinn.Rhodes@childrens.harvard.edu OI Songer, Thomas/0000-0002-5253-2514 FU Centers for Disease Control and Prevention [K01DP000089]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Fund; National Institute of Diabetes and Digestive and Kidney Diseases [K24DK082730]; New Balance Foundation; Bayer FX Supported by the Centers for Disease Control and Prevention (grant K01DP000089 to E. R.). Investigators were also supported by the Katherine Adler Astrove Youth Education Fund (to L. L.), Maria Griffin Drury Fund (to L. L.), National Institute of Diabetes and Digestive and Kidney Diseases (grant K24DK082730 to D. L.), and the New Balance Foundation (E. R. and D. L.). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies. E. R. was formerly Chief Medical Officer for Pediatric Weight Management Centers' Great Moves! Program, a company that was privately owned and operated in collaboration with the physicians of Children's Hospital Boston. E. R. provided contracted clinical and administrative services for the company, but neither had nor has equity or other economic interest in the business. E. R. also received salary support from an unrestricted, philanthropic grant from the New Balance Foundation. E.R.'s spouse owns stock in Bristol Meyers Squibb and Pfizer. L. L. is a consultant for Sanofi-Aventis, Johnson & Johnson, Lilly, Bristol Myers Squibb, Astra Zeneca, and Menarini and receives grant support from Bayer. The remaining authors declare no conflicts of interest. NR 40 TC 10 Z9 11 U1 3 U2 14 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 2012 VL 160 IS 6 DI 10.1016/j.jpeds.2011.11.026 PG 7 WC Pediatrics SC Pediatrics GA 946TC UT WOS:000304377300008 PM 22217471 ER PT J AU Shames, S Koczo, A Hahn, R Jin, ZZ Picard, MH Gillam, LD AF Shames, Sofia Koczo, Agnes Hahn, Rebecca Jin, Zhezhen Picard, Michael H. Gillam, Linda D. TI Flow Characteristics of the SAPIEN Aortic Valve: The Importance of Recognizing In-Stent Flow Acceleration for the Echocardiographic Assessment of Valve Function SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material DE Echocardiography; Transcatheter aortic valve ID DOPPLER-ECHOCARDIOGRAPHY; TRANSCATHETER; IMPLANTATION; STENOSIS; OUTCOMES; COREVALVE; RECOMMENDATIONS; VALIDATION; EXPERIENCE AB Background: The percutaneously implanted Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA) consists of cusps mounted within a stent. The individual impact of the stent and cusps on transvalvular flow and its implications for the echocardiographic assessment of valve function have not been previously reported. Methods: The study group consisted of 40 patients who underwent successful implantation with the SAPIEN valve. Pulsed Doppler was recorded with sample volumes immediately proximal to the stent (prestent), within the stent but proximal to the cusps (in-stent precusp), and distal to the cusps (in-stent postcusp). The Doppler velocity index and effective orifice area were calculated using both prestent and in-stent precusp velocities to represent "subvalvular" flow and continuous-wave recordings of the left ventricular outflow tract and aortic valve to represent postvalvular flow. Results: In all patients, there was flow acceleration at two levels: in-stent precusp and in-stent postcusp. The mean in-stent precusp peak velocities were significantly higher than the prestent values (1.5 +/- 0.2 vs 1.0 +/- 0.2 m/sec, P < .0001). Effective orifice area and Doppler velocity index calculated using the prestent versus in-stent precusp velocities were also significantly different (1.79 +/- 0.34 vs 2.54 +/- 0.46 cm(2), P < .0001, and 0.48 +/- 0.12 vs 0.73 +/- 0.13, P < .0001, respectively). Conclusions: The SAPIEN valve demonstrates flow acceleration at two levels, representing contributions of both the stent and valve cusps to the total valve gradient. Failure to recognize this phenomenon may result in inappropriate selection of the in-stent precusp pulsed Doppler spectrum to represent "subvalvular" flow, thereby overestimating the effective orifice area and Doppler velocity index. (J Am Soc Echocardiogr 2012;square:square-square-.) C1 [Shames, Sofia; Koczo, Agnes; Hahn, Rebecca] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, Div Cardiol, New York, NY 10032 USA. [Jin, Zhezhen] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gillam, Linda D.] Morristown Med Ctr, Dept Cardiovasc Med, Morristown, NJ USA. RP Gillam, LD (reprint author), Morristown Mem Hosp, Gagnon Cardiovasc Inst, Cardiac Adm 5, 100 Madison Ave, Morristown, NJ 07962 USA. EM linda.gillam@atlantichealth.org OI Picard, Michael/0000-0002-9264-3243 NR 18 TC 20 Z9 20 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 2012 VL 25 IS 6 BP 603 EP 609 DI 10.1016/j.echo.2012.02.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 946OK UT WOS:000304361700004 PM 22425590 ER PT J AU Perrault, LP Moskowitz, AJ Kron, IL Acker, MA Miller, MA Horvath, KA Thourani, VH Argenziano, M D'Alessandro, DA Blackstone, EH Moy, CS Mathew, JP Hung, J Gardner, TJ Parides, MK AF Perrault, Louis P. Moskowitz, Alan J. Kron, Irving L. Acker, Michael A. Miller, Marissa A. Horvath, Keith A. Thourani, Vinod H. Argenziano, Michael D'Alessandro, David A. Blackstone, Eugene H. Moy, Claudia S. Mathew, Joseph P. Hung, Judy Gardner, Timothy J. Parides, Michael K. TI Optimal surgical management of severe ischemic mitral regurgitation: To repair or to replace? SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID VALVULAR HEART-DISEASE; PAPILLARY-MUSCLE; NORMATIVE DATA; VALVE REPAIR; ANNULOPLASTY; RELIABILITY; DYSFUNCTION AB Background: Ischemic mitral regurgitation, a complication of myocardial infarction and coronary artery disease more generally, is associated with a high mortality rate and is estimated to affect 2.8 million Americans. With 1-year mortality rates as high as 40%, recent practice guidelines of professional societies recommend repair or replacement, but there remains a lack of conclusive evidence supporting either intervention. The choice between therapeutic options is characterized by the trade-off between reduced operative morbidity and mortality with repair versus a better long-term correction of mitral insufficiency with replacement. The long-term benefits of repair versus replacement remain unknown, which has led to significant variation in surgical practice. Methods and Results: This article describes the design of a prospective randomized clinical trial to evaluate the safety and effectiveness of mitral valve repair and replacement in patients with severe ischemic mitral regurgitation. This trial is being conducted as part of the Cardiothoracic Surgical Trials Network. This article addresses challenges in selecting a feasible primary end point, characterizing the target population (including the degree of mitral regurgitation) and analytical challenges in this high mortality disease. Conclusions: The article concludes by discussing the importance of information on functional status, survival, neurocognition, quality of life, and cardiac physiology in therapeutic decision making. (J Thorac Cardiovasc Surg 2012;143:1396-403) C1 [Moskowitz, Alan J.; Parides, Michael K.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, InCHOIR, New York, NY USA. [Perrault, Louis P.] Univ Montreal, Montreal Heart Inst, Dept Surg, Montreal, PQ, Canada. [Kron, Irving L.] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Acker, Michael A.] Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Miller, Marissa A.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Horvath, Keith A.] Suburban Hosp, NIH Heart Ctr, Bethesda, MD USA. [Thourani, Vinod H.] Emory Univ Hosp Midtown, Div Cardiothorac Surg, Atlanta, GA USA. [Argenziano, Michael] Columbia Univ, Med Ctr, Div Cardiothorac Surg, New York, NY USA. [D'Alessandro, David A.] Montefiore Einstein Heart Ctr, Dept Cardiovasc & Thorac Surg, New York, NY USA. [Blackstone, Eugene H.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. [Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Mathew, Joseph P.] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. [Hung, Judy] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gardner, Timothy J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA. RP Parides, MK (reprint author), Mt Sinai Sch Med, Dept Hlth Evidence & Policy, InCHOIR, New York, NY USA. EM michael.parides@mssm.edu OI Moskowitz, Alan/0000-0002-4412-9450 FU NHLBI NIH HHS [U01 HL088942, R01 HL092101] NR 31 TC 18 Z9 22 U1 1 U2 3 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 2012 VL 143 IS 6 BP 1396 EP 1403 DI 10.1016/j.jtcvs.2011.05.030 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 943HE UT WOS:000304110700025 PM 22054660 ER PT J AU Cuffe, S Bourredjem, A Graziano, S Pignon, JP Domerg, C Ezzalfani, M Seymour, L Strevel, E Burkes, R Capelletti, M Janne, PA Tsao, MS Shepherd, FA AF Cuffe, Sinead Bourredjem, Abderrahmane Graziano, Stephen Pignon, Jean-Pierre Domerg, Caroline Ezzalfani, Monia Seymour, Lesley Strevel, Elizabeth Burkes, Ronald Capelletti, Marzia Jaenne, Pasi A. Tsao, Ming-Sound Shepherd, Frances A. TI A Pooled Exploratory Analysis of the Effect of Tumor Size and KRAS Mutations on Survival Benefit From Adjuvant Platinum-Based Chemotherapy in Node-Negative Non-Small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; KRAS mutations; Adjuvant chemotherapy; TNM staging; Tumor size ID FORTHCOMING 7TH EDITION; VINORELBINE PLUS CISPLATIN; TNM CLASSIFICATION; STAGING PROJECT; PROGNOSTIC-SIGNIFICANCE; MALIGNANT-TUMORS; PROPOSALS; REVISION; RAS; GROUPINGS AB Introduction: The staging of node-negative non-small-cell lung cancer is modified in the 7th edition TNM classification. Here, we pool data from the National Cancer Institute of Canada Clinical Trials Group JBR. 10 trial and the Cancer and Leukemia Group B-9633 trial to explore the prognostic and predictive effects of the new T-size descriptors and KRAS mutation status. Methods: Node-negative patients were reclassified as T2a (>3-<= 5 cm), T2b (>5-<= 7 cm), T3 (>7 cm) or T <= 3 cm (<= 3 cm, but other T2 characteristics). Results: Of 538 eligible patients, 288 (53.5%) were T2a, 111 (21%) T2b, 62 (11.5%) T3, whereas 77 (14%) T <= 3 cm were excluded to avoid confounding. KRAS mutations were detected in 104 of 390 patients (27%). T-size was prognostic for disease-free survival (p = 0.03), but borderline for overall survival (OS; p = 0.10), on multivariable analysis. Significant interaction between the prognostic value of KRAS and tumor size was observed for OS (p = 0.01), but not disease-free survival (p = 0.10). There was a nonsignificant trend (p = 0.24) for increased chemotherapy effect on OS with advancing T-size (hazard ratio [HR] T2a 0.90, [0.63-1.30]; T2b 0.69, [0.38-1.24]; and T3 0.57, [0.28-1.17]). The HR for chemotherapy effect on OS in T2a patients with KRAS wild-type tumors was 0.81 (p = 0.36), whereas a trend for detrimental effect was observed in those with mutant tumors (HR 2.11; p = 0.09; interaction p = 0.05). Similar trends were observed in T2b to T3 patients with wild-type (HR 0.86; p = 0.62), and KRAS mutant tumors (HR 1.16; p = 0.74; interaction p = 0.58). Conclusion: Chemotherapy effect seems to increase with tumor size. However, this small study could not identify subgroups of patients who did or did not derive significant benefit from adjuvant chemotherapy based on T-size or KRAS status. C1 [Cuffe, Sinead; Tsao, Ming-Sound; Shepherd, Frances A.] Univ Hlth Network, Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada. [Cuffe, Sinead; Tsao, Ming-Sound; Shepherd, Frances A.] Univ Toronto, Toronto, ON, Canada. [Bourredjem, Abderrahmane; Pignon, Jean-Pierre; Domerg, Caroline; Ezzalfani, Monia] Inst Gustave Roussy, Dept Biostat & Epidemiol, Villejuif, France. [Graziano, Stephen] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. [Seymour, Lesley] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. [Strevel, Elizabeth] Credit Valley Hosp, Dept Med Oncol, Mississauga, ON, Canada. [Burkes, Ronald] Mt Sinai Hosp, Dept Med Oncol, Toronto, ON M5G 1X5, Canada. [Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shepherd, FA (reprint author), Univ Hlth Network, Princess Margaret Hosp, Dept Med Oncol & Hematol, Suite 5-104,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM frances.shepherd@uhn.on.ca FU French Ligue Nationale Contre le Cancer; Sanofi; Canadian Cancer Society; National Cancer Institute of the United States; National Cancer Institute [CA31946, CA33601] FX Supported by the French Ligue Nationale Contre le Cancer and an unrestricted grant from Sanofi. The JBR. 10 trial was supported by the Canadian Cancer Society and the National Cancer Institute of the United States. The research for CALGB 9633 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (M.M.B.) and to the CALGB Statistical Center (D.J.S., CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the official views of the National Cancer Institute. NR 29 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2012 VL 7 IS 6 BP 963 EP 972 DI 10.1097/JTO.0b013e31824fe9e6 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 943IK UT WOS:000304114000003 PM 22588152 ER PT J AU Westover, KD Seco, J Adams, JA Lanuti, M Choi, NC Engelsman, M Willers, H AF Westover, Kenneth D. Seco, Joao Adams, Judith A. Lanuti, Michael Choi, Noah C. Engelsman, Martijn Willers, Henning TI Proton SBRT for Medically Inoperable Stage I NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Stereotactic body radiation therapy; Proton therapy; Non-small-cell lung cancer ID STEREOTACTIC BODY RADIOTHERAPY; CELL LUNG-CARCINOMA; RADIATION-THERAPY; QUALITY-ASSURANCE; BEAM RADIOTHERAPY; CANCER; TUMORS; TOXICITY AB Introduction: The physical properties of proton beam radiation may offer advantages for treating patients with non-small-cell lung cancer (NSCLC). However, its utility for the treatment of medically inoperable stage I NSCLC patients with stereotactic body radiation therapy (SBRT) is unknown. Methods: Outcomes for patients with medically inoperable stage I NSCLC treated with proton SBRT were retrospectively analyzed. Proton SBRT was selected as the treatment modality based on pulmonary comorbidities (n = 5), prior chest radiation or/and multiple primary tumors (n = 7), or other reasons (n = 3). Treatments were administered using 2 to 3 proton beams. Treatment toxicity was scored according to common toxicity criteria for adverse events version 4 criteria. Results: Fifteen consecutive patients and 20 tumors were treated with proton SBRT to 42 to 50 Gy(relative biological effectiveness) in 3 to 5 fractions between July 2008 and September 2010. Treatments were well tolerated with only one case of grade 2 fatigue, one case of grade 2 dermatitis, three cases of rib fracture (maximum grade 2), and one case of grade 3 pneumonitis in a patient with severe chronic obstructive pulmonary disease. With a median follow-up of 24.1 months, 2-year overall survival and local control rates were 64% (95% confidence limits, 34%-83%) and 100% (83%-100%), respectively. Conclusions: We conclude that proton SBRT is effective and well tolerated in this unfavorable group of patients. Prospective clinical trials testing the utility of proton SBRT in stage I NSCLC are warranted. C1 [Seco, Joao; Adams, Judith A.; Engelsman, Martijn; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Phys, Boston, MA 02114 USA. [Westover, Kenneth D.] Harvard Radiat Oncol Program, Boston, MA USA. [Lanuti, Michael] Harvard Univ, Sch Med, Dept Surg, Div Thorac Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Phys, Cox 3,55 Fruit St, Boston, MA 02114 USA. EM hwillers@partners.org RI Seco, Joao/J-4451-2012 FU Federal Share of program; Proton Therapy Research and Treatment Center [C06 CA059267] FX The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 23 TC 22 Z9 23 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2012 VL 7 IS 6 BP 1021 EP 1025 DI 10.1097/JTO.0b013e31824de0bf PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 943IK UT WOS:000304114000010 PM 22551902 ER PT J AU Oxnard, GR Miller, VA Robson, ME Azzoli, CG Pao, W Ladanyi, M Arcila, ME AF Oxnard, Geoffrey R. Miller, Vincent A. Robson, Mark E. Azzoli, Christopher G. Pao, William Ladanyi, Marc Arcila, Maria E. TI Screening for Germline EGFR T790M Mutations Through Lung Cancer Genotyping SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITORS; SUSCEPTIBILITY LOCUS; NEVER-SMOKERS; ADENOCARCINOMAS; RESISTANCE AB Introduction: The study of patients carrying germline endothelial growth factor receptor (EGFR) mutations, which have been found in cases of familial lung adenocarcinoma, could provide unique insight into lung cancer risk and carcinogenesis in never-smokers. However, investigations into the biology of germline EGFR mutations have been hampered by the lack of an effective strategy for screening for carriers. We hypothesized that patients with lung cancers found to harbor the EGFR T790M resistance mutation before treatment, an uncommon occurrence, would be likely to carry underlying germline T790M mutations. Methods: Eleven unrelated patients with lung cancer, harboring an EGFR T790M mutation, were identified from a 7-year institutional experience with tumor genotyping. Ten patients had benign tissue available, which was anonymously tested for the presence of germline EGFR mutations. Results: Five of 10 cases carried a germline T790M mutation (50%, confidence interval 27%-73%). One patient's cancer exhibited a distinctive indolent growth, which has also been described in preclinical studies of T790M-mutant cancers. A second patient underwent resection of six separate primary lung adenocarcinomas, each carrying different sensitizing EGFR mutations and T790M. Conclusions: Genotyping of lung cancers, now commonly performed to predict benefit from treatment with EGFR tyrosine kinase inhibitors, can also be used as a screening tool to identify patients at risk of carrying germline EGFR mutations. Once identified, these patients and their families can be studied prospectively to explore appropriate lung cancer screening strategies. Further studies using existing oncogenomic data to provide insight into underlying germline genetics are warranted. C1 [Oxnard, Geoffrey R.; Miller, Vincent A.; Azzoli, Christopher G.] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Dept Med, New York, NY 10021 USA. [Robson, Mark E.] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. [Ladanyi, Marc; Arcila, Maria E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, Mol Diagnost Serv, New York, NY 10021 USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1234, Boston, MA 02215 USA. EM goxnard@partners.org RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Robson, Mark/0000-0002-3109-1692 FU National Cancer Institute; Astra-Zeneca; Enzon; Xcovery; Symphogen; American Society of Clinical Oncology; National Cancer Institute at the National Institutes of Health [P01-CA129243] FX Vincent A. Miller's institution has received a P01 grant from the National Cancer Institute and he hold patents relating to this work. Christopher G. Azzoli's institution has received a P01 grant from the National Cancer Institute. Geoffrey R. Oxnard's institution has received a P01 grant from the National Cancer Institute, and he has served on the advisory board of Genentech. Mark Robson has served as a consultant to Sanofi-Aventis, Abbott, Pfizer, and General Electric, and has received grants from Astra-Zeneca. Marc Ladanyi has served as a consultant to Astra Zeneca (Canada), Daiichi-Sankyo, and Genzyme. William Pao serves as a consultant to MolecularMD, AstraZeneca, Bristol-Myers Squibb, Symphony Evolution, and Clovis Oncology. William Pao has received grants from Enzon, Xcovery, AstraZeneca, and Symphogen. Rights to EGFR T790M testing were licensed on behalf of William Pao and others by MSKCC to MolecularMD.; Supported in part by a Young Investigator Award from the American Society of Clinical Oncology; and from the National Cancer Institute at the National Institutes of Health (P01-CA129243). NR 18 TC 38 Z9 38 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2012 VL 7 IS 6 BP 1049 EP 1052 DI 10.1097/JTO.0b013e318250ed9d PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 943IK UT WOS:000304114000014 PM 22588155 ER PT J AU Lo, RC Bensley, RP Hamdan, AD Wyers, M Chaikof, E Adams, JE Schermerhorn, ML AF Lo, Ruby C. Bensley, Rodney P. Hamdan, Allen D. Wyers, Mark Chaikof, Elliot Adams, Julie E. Schermerhorn, Marc L. TI Gender Differences in Aortic Aneurysm Presentation, Repair, and Mortality in the VSGNE SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY JUN 07-09, 2012 CL Natl Harbor, MD SP Soc Vasc Surg (SVS) C1 [Lo, Ruby C.; Bensley, Rodney P.; Hamdan, Allen D.; Wyers, Mark; Chaikof, Elliot; Schermerhorn, Marc L.] BIDMC, Boston, MA USA. [Adams, Julie E.] Univ Vermont, Coll Med, Burlington, VT USA. NR 0 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2012 VL 55 IS 6 SU S BP 10 EP 11 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 947AL UT WOS:000304398900016 ER PT J AU Kang, JW Patel, VI Mukhopadhyay, S Garg, A Cambria, MR Conrad, MF LaMuraglia, GM Cambria, RP AF Kang, Jeanwan Patel, Virendra I. Mukhopadhyay, Shankha Garg, Ashu Cambria, Matthew R. Conrad, Mark F. LaMuraglia, Glenn M. Cambria, Richard P. TI Long-term Clinical and Anatomic Outcomes Following Carotid Endarterectomy SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY JUN 07-09, 2012 CL Natl Harbor, MD SP Soc Vasc Surg (SVS) C1 [Kang, Jeanwan; Patel, Virendra I.; Mukhopadhyay, Shankha; Garg, Ashu; Cambria, Matthew R.; Conrad, Mark F.; LaMuraglia, Glenn M.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2012 VL 55 IS 6 SU S BP 12 EP 13 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 947AL UT WOS:000304398900020 ER PT J AU Wang, JY Gupta, N Raffetto, JD Haider, SA Silva, R Ebaugh, JL Sulkin, M Fox, R AF Wang, Jeffrey Y. Gupta, Naren Raffetto, Joseph D. Haider, Shan-Ali Silva, Richard Ebaugh, James L. Sulkin, Michael Fox, Robert TI Ambulatory Venous Thrombectomy for Acute Deep Venous Thrombosis SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY JUN 07-09, 2012 CL Natl Harbor, MD SP Soc Vasc Surg (SVS) C1 [Wang, Jeffrey Y.; Haider, Shan-Ali; Silva, Richard; Sulkin, Michael; Fox, Robert] Shady Grove Adventist Hosp, Rockville, MD USA. [Gupta, Naren; Raffetto, Joseph D.; Ebaugh, James L.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2012 VL 55 IS 6 SU S BP 102 EP 102 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 947AL UT WOS:000304398900195 ER PT J AU Danczyk, RC Mitchell, EL Burk, C Singh, S Liem, TK Landry, GJ Petersen, BD Moneta, GL AF Danczyk, Rachel C. Mitchell, Erica L. Burk, Chad Singh, Sarguni Liem, Timothy K. Landry, Gregory J. Petersen, Bryan D. Moneta, Gregory L. TI Comparing patient outcomes between multiple ipsilateral iliac artery stents and isolated iliac artery stents SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Western-Vascular-Society CY SEP 17-20, 2011 CL Kauai, HI SP Western Vasc Soc ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; AORTOILIAC OCCLUSIVE DISEASE; CONSENSUS-CLASS-C; ENDOVASCULAR TREATMENT; PREDICTORS; LESIONS; MULTICENTER; EXPERIENCE; ISCHEMIA; THERAPY AB Objective: Endovascular stents are accepted therapy for iliac artery stenoses and occlusions. Surgery is the recommended therapy for patients with severe iliac artery disease, including those with the combination of ipsilateral common iliac artery (CIA) and external iliac artery (EIA) stenoses/occlusions. This study compared patient outcomes, including late open conversion rates, for combined ipsilateral CIA and EIA stenting vs CIA or EIA stents alone. Methods: Between 1998 and 2010, 588 patients underwent iliac artery stenting at two institutions. Patient comorbidities and outcomes were retrospectively reviewed, and analyses were performed using multivariate regression and Kaplan-Meier methods. Results: There were 436 extremities with CIA stents, 195 with EIA stents, and 157 with CIA and EIA stents. The groups did not differ significantly in demographics, comorbidities, or treatment indications. During follow-up, 183 patients died, 95 underwent an endovascular reintervention, and 48 required late open conversion. For patients in the CIA or EIA stent group, the mean +/- standard error survival was 5.3 +/- 0.3 years, secondary endovascular intervention-free survival was 7.4 +/- 0.6 years, late open conversion-free survival was 9.8 +/- 0.4 years, and amputation-free survival was 7.6 +/- 0.4 years. In the CIA and EIA stent group, survival was 6.1 +/- 0.6 years, secondary endovascular intervention-free survival was 7.2 +/- 0.6 years, late open conversion-free survival was 9.0 +/- 1.1 years, and amputation-free survival was 8.4 +/- 0.5 years. Survival, reintervention-free survival, late open conversion-free survival, and amputation-free survival were all similar between patient groups (all P > .05). CIA and EIA stenting in combination was not a predictor of death, reintervention, late open conversion, or amputation. Conclusions: Outcomes are similar for patients with CIA or EIA stents and for those with combined ipsilateral CIA and EIA stents. Late open conversions for iliac artery stent failure are uncommon and not influenced by the location or extent of prior iliac artery stent placement. Endovascular therapy for aortoiliac disease should be extended to consider selected patients with ipsilateral CIA and EIA stenoses/occlusions. (J Vasc Surg 2012; 55: 1637-46.) C1 [Danczyk, Rachel C.; Mitchell, Erica L.; Burk, Chad; Singh, Sarguni; Liem, Timothy K.; Landry, Gregory J.; Moneta, Gregory L.] Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97239 USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Dotter Inst, Portland, OR 97239 USA. [Petersen, Bryan D.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Mitchell, EL (reprint author), Oregon Hlth & Sci Univ, Div Vasc Surg, OP11, Portland, OR 97239 USA. EM mitcheer@ohsu.edu NR 21 TC 3 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2012 VL 55 IS 6 BP 1637 EP U411 DI 10.1016/j.jvs.2011.12.048 PG 16 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 944MF UT WOS:000304206000014 PM 22360919 ER PT J AU Raffetto, JD Yu, P Reslan, OM Xia, Y Khalil, RA AF Raffetto, Joseph D. Yu, Peng Reslan, Ossama M. Xia, Yin Khalil, Raouf A. TI Endothelium-dependent nitric oxide and hyperpolarization-mediated venous relaxation pathways in rat inferior vena cava SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Venous-Forum CY FEB 23-26, 2011 CL San Diego, CA SP Amer Venous Forum ID POTASSIUM CHANNEL OPENERS; VARICOSE-VEIN FORMATION; K+-CHANNELS; HYDROGEN-PEROXIDE; SAPHENOUS-VEIN; SMALL ARTERIES; FEMORAL VEINS; PREGNANT RATS; FACTOR EDHF; CYCLIC-GMP AB Introduction: The vascular endothelium plays a major role in the control of arterial tone; however, its role in venous tissues is less clear. The purpose of this study was to determine the role of endothelium in the control of venous function and the relaxation pathways involved. Methods: Circular segments of inferior vena cava (IVC) from male Sprague-Dawley rats were suspended between two wires and isometric contraction to phenylephrine (Phe; 10(-5)M) and 96 mM KCl was measured. Acetylcholine (Ach; 10(-10) to 10(-5)M) was added and the percentage of venous relaxation was measured. To determine the role of nitric oxide (NO) and prostacyclin (PGI(2)), vein relaxation was measured in the presence of the nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-4) M) and the cyclooxygenase inhibitor indomethacin (10(-5) M). To measure the role of hyperpolarization, vein relaxation was measured in the presence of K+ channel activator cromakalim (10(-11) to 10(-6) M), and the nonselective K+ channel blocker tetraethylammonium (TEA; 10(-3) M). To test for the contribution of a specific K+ channel, the effects of K+ channel blockers: glibenclamide (adenosine triphosphate [ATP]-sensitive K-ATP, 10(-5) M), 4-aminopyridine (4-AP; voltage-dependent K-v, 10(-3) M), apamin (small conductance Ca2+-dependent SKCa, 10(-7) M), and iberiotoxin (large conductance Ca2+-dependent BKCa, 10(-8) M) on Ach-induced relaxation were tested. Results: Ach caused concentration-dependent relaxation of Phe contraction (maximum 49.9 +/- 4.9%). Removal of endothelium abolished Ach-induced relaxation. IVC treatment with L-NAME partially reduced Ach relaxation (32.8 +/- 4.9%). In IVC treated with L-NAME plus indomethacin, significant Ach-induced relaxation (33.6 +/- 3.2%) could still be observed, suggesting a role of endothelium-derived hyperpolarizing factor (EDHF). In IVC treated with L-NAME, indomethacin and TEA, Ach relaxation was abolished, supporting a role of EDHF. In veins stimulated with high KCl, Ach caused relaxation (maximum 59.5 +/- 3.5%) that was abolished in the presence of L-NAME and indomethacin suggesting that any Ach-induced EDHF is blocked in the presence of high KCl depolarizing solution, which does not favor outward movement of K+ ion and membrane hyperpolarization. Cromakalim, an activator of K-ATP, caused significant IVC relaxation when applied alone or on top of maximal Ach-induced relaxation, suggesting that the Ach response may not involve K-ATP. Ach-induced relaxation was not inhibited by glibenclamide, 4-AP, or apamin, suggesting little role of K-ATP, K-v or SKCa, respectively. In contrast, iberiotoxin significantly inhibited Ach-induced relaxation, suggesting a role of BKCa. Conclusions: Thus, endothelium-dependent venous relaxation plays a major role in the control of venous function. In addition to NO, an EDHF pathway involving BKCa may play a role in endothelium-dependent venous relaxation. (J Vasc Surg 2012;55:1716-25.) C1 [Raffetto, Joseph D.; Khalil, Raouf A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Raffetto, Joseph D.; Yu, Peng; Reslan, Ossama M.; Xia, Yin; Khalil, Raouf A.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA. RP Khalil, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc Surg, 75 Francis St, Boston, MA 02115 USA. EM raouf_khalil@hms.harvard.edu FU NHLBI NIH HHS [R21 HL098724, R21 HL098724-01A1, R01 HL065998-10, HL-98724, R01 HL065998, R01 HL065998-09, R01 HL070659-05, R01 HL070659, HL-65998, R21 HL098724-02]; NICHD NIH HHS [HD-60702, R03 HD060702-01, R03 HD060702-02, R03 HD060702] NR 57 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2012 VL 55 IS 6 BP 1716 EP 1725 DI 10.1016/j.jvs.2011.10.124 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 944MF UT WOS:000304206000025 PM 22209615 ER PT J AU Moldt, B Shibata-Koyama, M Rakasz, EG Schultz, N Kanda, Y Dunlop, DC Finstad, SL Jin, CG Landucci, G Alpert, MD Dugast, AS Parren, PWHI Nimmerjahn, F Evans, DT Alter, G Forthal, DN Schmitz, JE Iida, S Poignard, P Watkins, DI Hessell, AJ Burton, DR AF Moldt, Brian Shibata-Koyama, Mami Rakasz, Eva G. Schultz, Niccole Kanda, Yutaka Dunlop, D. Cameron Finstad, Samantha L. Jin, Chenggang Landucci, Gary Alpert, Michael D. Dugast, Anne-Sophie Parren, Paul W. H. I. Nimmerjahn, Falk Evans, David T. Alter, Galit Forthal, Donald N. Schmitz, Jorn E. Iida, Shigeru Poignard, Pascal Watkins, David I. Hessell, Ann J. Burton, Dennis R. TI A Nonfucosylated Variant of the anti-HIV-1 Monoclonal Antibody b12 Has Enhanced Fc gamma RIIIa-Mediated Antiviral Activity In Vitro but Does Not Improve Protection against Mucosal SHIV Challenge in Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; SIMIAN IMMUNODEFICIENCY VIRUS; HIV PRECLINICAL INTERVENTIONS; EFFECTOR-CELLS; NEUTRALIZING ANTIBODIES; NONHUMAN-PRIMATES; BINDING; RESPONSES; RECEPTOR; INFECTION AB Eliciting neutralizing antibodies is thought to be a key activity of a vaccine against human immunodeficiency virus (HIV). However, a number of studies have suggested that in addition to neutralization, interaction of IgG with Fc gamma receptors (Fc gamma R) may play an important role in antibody-mediated protection. We have previously obtained evidence that the protective activity of the broadly neutralizing human IgG1 anti-HIV monoclonal antibody (MAb) b12 in macaques is diminished in the absence of Fc gamma R binding capacity. To investigate antibody-dependent cellular cytotoxicity (ADCC) as a contributor to Fc gamma R-associated protection, we developed a nonfucosylated variant of b12 (NFb12). We showed that, compared to fully fucosylated (referred to as wild-type in the text) b12, NFb12 had higher affinity for human and rhesus macaque Fc gamma RIIIa and was more efficient in inhibiting viral replication and more effective in killing HIV-infected cells in an ADCC assay. Despite these more potent in vitro antiviral activities, NFb12 did not enhance protection in vivo against repeated low-dose vaginal challenge in the simian-human immunodeficiency virus (SHIV)/macaque model compared to wild-type b12. No difference in protection, viral load, or infection susceptibility was observed between animals given NFb12 and those given fully fucosylated b12, indicating that Fc gamma R-mediated activities distinct from Fc gamma RIIIa-mediated ADCC may be important in the observed protection against SHIV challenge. C1 [Moldt, Brian; Schultz, Niccole; Dunlop, D. Cameron; Poignard, Pascal; Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Moldt, Brian; Schultz, Niccole; Dunlop, D. Cameron; Poignard, Pascal; Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA USA. [Shibata-Koyama, Mami; Kanda, Yutaka] Kyowa Hakko Kirin Calif Inc, La Jolla, CA USA. [Rakasz, Eva G.; Watkins, David I.] Univ Wisconsin Madison, Dept Pathol, Madison, WI USA. [Rakasz, Eva G.; Watkins, David I.] Univ Wisconsin Madison, Lab Med, Madison, WI USA. [Finstad, Samantha L.; Jin, Chenggang; Schmitz, Jorn E.] Harvard Univ, Sch Med, Beth Israel Med Ctr, Div Vial Pathogenesis, Boston, MA USA. [Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Alpert, Michael D.; Evans, David T.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA USA. [Dugast, Anne-Sophie; Alter, Galit; Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, Massachusetts Inst Technol & Harvard, Boston, MA USA. [Parren, Paul W. H. I.] Genmab, Utrecht, Netherlands. [Nimmerjahn, Falk] Univ Erlangen Nurnberg, Inst Genet, Dept Biol, D-91054 Erlangen, Germany. [Iida, Shigeru] Kyowa Hakko Kirin, Tokyo, Japan. [Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY USA. [Hessell, Ann J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Hessell, Ann J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM hessell@ohsu.edu; burton@scripps.edu RI Nimmerjahn, Falk/J-4986-2013; poignard, pascal/N-6678-2013; Dugast, AnneSophie/L-9541-2015; OI Finstad, Samantha/0000-0002-3460-6428; Nimmerjahn, Falk/0000-0002-5418-316X FU NIH/NIAID [R01 AI055332]; Center for HIV/AIDS Vaccine Immunology NIAID [U19 AI067854]; International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium; The Ragon Institute of MGH; The Ragon Institute of MIT; The Ragon Institute of Harvard; Alfred Benzon Fellowship FX This work was funded by NIH/NIAID grant R01 AI055332 (D.R.B.), by the Center for HIV/AIDS Vaccine Immunology NIAID grant U19 AI067854 (S.L.F., C.J., and J.E.S.), by the International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium (D.R.B.), by The Ragon Institute of MGH, MIT, and Harvard, and by an Alfred Benzon Fellowship (B.M.). NR 50 TC 58 Z9 58 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2012 VL 86 IS 11 BP 6189 EP 6196 DI 10.1128/JVI.00491-12 PG 8 WC Virology SC Virology GA 944UM UT WOS:000304229300020 PM 22457527 ER PT J AU Abel, GA Vanderplas, A Rodriguez, MA Crosby, AL Czuczman, MS Niland, JC Gordon, LI Millenson, M Zelenetz, AD Friedberg, JW LaCasce, AS AF Abel, Gregory A. Vanderplas, Ann Rodriguez, Maria A. Crosby, Allison L. Czuczman, Myron S. Niland, Joyce C. Gordon, Leo I. Millenson, Michael Zelenetz, Andrew D. Friedberg, Jonathan W. LaCasce, Ann S. TI High rates of surveillance imaging for treated diffuse large B-cell lymphoma: findings from a large national database SO LEUKEMIA & LYMPHOMA LA English DT Article DE Diff use large B-cell lymphoma; diagnostic imaging; health services research ID NON-HODGKINS-LYMPHOMA; POSITRON-EMISSION-TOMOGRAPHY; FOLLOW-UP; COMPLETE REMISSION; CANCER; RELAPSE; SCANS; PET AB We aimed to characterize surveillance imaging and circumstances of relapse for patients with diffuse large B-cell lymphoma (DLBCL) in the National Comprehensive Cancer Network Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting clinical and outcome data at seven comprehensive cancer centers. Patients presenting with newly diagnosed DLBCL in remission >= 3 months after initial therapy and who had accrued 2 years of follow-up were eligible for analysis (n = 625). The median number of imaging studies was 2.5/year (institutional range 0.5-3.5, p < 0.0001); 48.4% received only dedicated computed tomography (CT) scans, 14.6% received only positron emission tomography (PET)-inclusive modalities, 32.8% received a combination and 4.2% received no imaging. Among all eligible patients, 50 (8.0%) experienced relapse, and approximately one-quarter of subclinical relapses were detected through routine imaging. Our results suggest that despite limited data regarding its effect on outcomes, surveillance imaging is prevalent in DLBCL, and a majority of patients receive PET scans at some point during follow-up. C1 [Abel, Gregory A.; Crosby, Allison L.; Niland, Joyce C.; LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abel, Gregory A.; LaCasce, Ann S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Vanderplas, Ann] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Rodriguez, Maria A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gordon, Leo I.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Friedberg, Jonathan W.] James P Wilmot Canc Ctr, Rochester, NY USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Gregory_Abel@dfci.harvard.edu OI Zelenetz, Andrew/0000-0003-1403-6883; Gordon, Leo/0000-0003-1666-7064 NR 18 TC 20 Z9 20 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2012 VL 53 IS 6 BP 1113 EP 1116 DI 10.3109/10428194.2011.639882 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 945XZ UT WOS:000304311500017 PM 22098406 ER PT J AU Lane, AA Armand, P Feng, Y Neuberg, DS Abramson, JS Brown, JR Fisher, DC LaCasce, AS Jacobsen, ED McAfee, SL Spitzer, TR Freedman, AS Chen, YB AF Lane, Andrew A. Armand, Philippe Feng, Yang Neuberg, Donna S. Abramson, Jeremy S. Brown, Jennifer R. Fisher, David C. LaCasce, Ann S. Jacobsen, Eric D. McAfee, Steven L. Spitzer, Thomas R. Freedman, Arnold S. Chen, Yi-Bin TI Risk factors for development of pneumonitis after high-dose chemotherapy with cyclophosphamide, BCNU and etoposide followed by autologous stem cell transplant SO LEUKEMIA & LYMPHOMA LA English DT Article DE Transplant toxicity; clinical results; lymphoma and Hodgkin disease ID BONE-MARROW-TRANSPLANTATION; REFRACTORY HODGKINS-DISEASE; BREAST-CANCER; LYMPHOID MALIGNANCIES; PREPARATIVE REGIMENS; CARMUSTINE; TOXICITY; THERAPY; EFFICACY AB Pneumonitis is a complication of high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) regimens containing BCNU. Our goal was to define the incidence and risk factors for pneumonitis in patients with lymphoma receiving a uniform conditioning regimen in the modern era. We studied 222 patients who received HDC-ASCT using cyclophosphamide, BCNU and VP-16 (CBV). Pneumonitis incidence was 22%, with 19% receiving systemic corticosteroid treatment and 8% requiring inpatient hospitalization for pneumonitis. Three patients died secondary to pneumonitis-related complications. The following variables were independently associated with pneumonitis: prior mediastinal radiation (odds ratio [OR] 6.5, 95% confi dence interval [CI] 2.3 -18.9, p = 0.0005), total BCNU dose above 1000 mg (OR 3.4, 95% CI 1.3-8.7, p = 0.012) and age less than 54 (OR 3.0, 95% CI 1.4-6.5, p = 0.0037). Increased vigilance for symptoms of pneumonitis is warranted for patients with prior mediastinal radiation and for younger patients, and dose reduction may be considered for patients who would receive greater than 1000 mg of BCNU. C1 [Chen, Yi-Bin] Massachusetts Gen Hosp, Dept Hematol Oncol, Div Bone Marrow Transplantat, Ctr Canc, Boston, MA 02114 USA. [Lane, Andrew A.; Armand, Philippe; Brown, Jennifer R.; Fisher, David C.; LaCasce, Ann S.; Jacobsen, Eric D.; Freedman, Arnold S.; Chen, Yi-Bin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Feng, Yang; Neuberg, Donna S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Div Bone Marrow Transplantat, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU Leukemia & Lymphoma Society; NIH [T32 CA071345] FX Y.-B.C. is a recipient of a career development award from the Leukemia & Lymphoma Society. Additional support provided was by NIH T32 CA071345 (A.A.L.). NR 28 TC 9 Z9 9 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2012 VL 53 IS 6 BP 1130 EP 1136 DI 10.3109/10428194.2011.645208 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 945XZ UT WOS:000304311500020 PM 22132836 ER PT J AU Wiernik, PH Li, HL Weller, E Hochster, HS Horning, SJ Nazeer, T Gordon, LI Habermann, TM Minniti, CJ Shapiro, GR Cassileth, PA AF Wiernik, Peter H. Li, Hailun Weller, Edie Hochster, Howard S. Horning, Sandra J. Nazeer, Tipu Gordon, Leo I. Habermann, Thomas M. Minniti, Carl J., Jr. Shapiro, Gary R. Cassileth, Peter A. TI Activity of topotecan 21-day infusion in patients with previously treated large cell lymphoma: long-term follow-up of an Eastern Cooperative Oncology Group study (E5493) SO LEUKEMIA & LYMPHOMA LA English DT Article DE Lymphoma and Hodgkin disease; chemotherapeutic approaches; topotecan ID NON-HODGKINS-LYMPHOMA; CHRONIC MYELOMONOCYTIC LEUKEMIA; EPITHELIAL OVARIAN-CANCER; PHASE-II; TOPOISOMERASE-I; CAMPTOTHECIN; LENALIDOMIDE; MALIGNANCIES; PACLITAXEL; INHIBITOR AB The purpose of this study was to determine the activity of topotecan given by 21-day continuous infusion in patients previously treated with one prior therapy for a diffuse large-cell lymphoma or immunoblastic lymphoma. Patients with appropriate histology and measurable disease who had been treated with one prior chemotherapy regimen were eligible for study. Slides of tumor biopsies were submitted for central review of pathology. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 and adequate bone marrow function. Patients were treated with continuous infusion topotecan, 0.4 mg/m(2)/day x 21 days. Therapy could be escalated to 0.5 and then 0.6 mg/m(2)/day in subsequent cycles if there was no dose-limiting toxicity at the initial dose level. Patients were treated with two cycles after achieving a complete response or until disease progression or unacceptable toxicity occurred. Thirty-seven patients were enrolled. However, only 26 cases were eligible due to a performance status of > 2 (n = 2), more than one prior chemotherapy (n = 1) and wrong histology on review (n = 8). Due to the unexpectedly high ineligibility rate, two sets of analysis were done for all 37 patients enrolled and for the 26 eligible patients, respectively. Of the 37 patients (15 males and 22 females), the International Prognostic Index included 11% low risk, 30% low intermediate risk, 46% high intermediate risk and 8% high risk. The median follow-up was 77 months. A total of 136 cycles of therapy were given with a median of 3 cycles per patient. Grade 4 toxicities included: 14% grade 4 thrombocytopenia; 14% grade 4 granulocytopenia, 8% leukopenia, 3% each anemia, hemorrhage, infection, vomiting, thrombosis, liver toxicity and neuromotor toxicity. The response analysis including all 37 patients showed five complete responses (CRs) and four partial responses (PRs) for a total response rate of 24% (90% two-stage confidence interval 13-39%). Median progression-free survival (PFS) was 3.7 months, with 1- and 2-year PFS of 21% and 6%, respectively (90% confidence interval 11-34% and 2-15%). Median overall survival (OS) was 10.5 months, with 1- and 2-year OS of 41% and 27%, respectively (90% confidence interval 27-53% and 16-39%). Analysis including only eligible patients showed similar response rates and survival outcomes. Single agent topotecan has moderate activity for previously treated high-grade lymphoma equivalent to that of several newer agents, and should be considered for incorporation into multi-drug salvage chemotherapy programs. C1 [Wiernik, Peter H.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Wiernik, Peter H.] St Lukes Roosevelt Hosp, New York, NY USA. [Li, Hailun; Weller, Edie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hochster, Howard S.] NYU, Sch Med, New York, NY USA. [Horning, Sandra J.] Stanford Univ, Stanford, CA 94305 USA. [Nazeer, Tipu] Albany Med Coll, Albany, NY 12208 USA. [Gordon, Leo I.] Northwestern Univ, Chicago, IL 60611 USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Minniti, Carl J., Jr.] Minniti Ctr Oncol Hematol, Mickleton, NJ USA. [Shapiro, Gary R.] Aurora Sinai Med Ctr, Milwaukee, WI USA. [Cassileth, Peter A.] Univ Miami, Miami, FL USA. RP Wiernik, PH (reprint author), Montefiore N Div, Ctr Canc, 600 E 233rd St, Bronx, NY 10466 USA. EM pwiernik@aol.com OI Gordon, Leo/0000-0003-1666-7064 FU Public Health Service [CA23318, CA66636, CA21115, CA14958, CA17145, CA13650, CA27525, CA 16116, CA21076]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA14958, CA17145, CA13650, CA27525, CA 16116, CA21076 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 21 TC 4 Z9 4 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2012 VL 53 IS 6 BP 1137 EP 1142 DI 10.3109/10428194.2011.643406 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 945XZ UT WOS:000304311500021 PM 22111940 ER PT J AU Cook, DB Stegner, AJ Nagelkirk, PR Meyer, JD Togo, F Natelson, BH AF Cook, Dane B. Stegner, Aaron J. Nagelkirk, Paul R. Meyer, Jacob D. Togo, Fumiharu Natelson, Benjamin H. TI Responses to Exercise Differ for Chronic Fatigue Syndrome Patients with Fibromyalgia SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE PAIN; FATIGUE; IMPEDANCE CARDIOGRAPHY; STROKE VOLUME; RPE ID PHYSIOLOGICAL-RESPONSES; CARDIOVASCULAR-RESPONSE; RESISTANCE EXERCISE; WOMEN; ILLNESS; MUSCLE; PAIN; SYMPTOMS; CAPACITY AB COOK, D. B., A. J. STEGNER, P. R. NAGELKIRK, J. D. MEYER, F. TOGO, and B. H. NATELSON. Responses to Exercise Differ for Chronic Fatigue Syndrome Patients with Fibromyalgia. Med. Sci. Sports Exerc., Vol. 44, No. 6, pp. 1186-1193, 2012. Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion. Purpose: The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls. Methods: Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response. Results: There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls. Conclusions: The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise. C1 [Cook, Dane B.; Stegner, Aaron J.; Meyer, Jacob D.] Univ Wisconsin Madison, Dept Kinesiol, Madison, WI 53706 USA. [Cook, Dane B.; Stegner, Aaron J.] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI USA. [Nagelkirk, Paul R.] Ball State Univ, Sch Phys Educ Sport & Exercise Sci, Muncie, IN 47306 USA. [Togo, Fumiharu] Univ Tokyo, Grad Sch Educ, Tokyo, Japan. [Natelson, Benjamin H.] Beth Israel Deaconess Med Ctr, Pain & Fatigue Study Ctr, New York, NY 10003 USA. RP Cook, DB (reprint author), Univ Wisconsin Madison, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu FU National Institutes of Health [AI-32247] FX This research was supported by the National Institutes of Health grant AI-32247. NR 40 TC 10 Z9 10 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2012 VL 44 IS 6 BP 1186 EP 1193 DI 10.1249/MSS.0b013e3182417b9a PG 8 WC Sport Sciences SC Sport Sciences GA 944TQ UT WOS:000304227100027 PM 22157881 ER PT J AU Morioka, T Dishinger, JF Reid, KR Liew, CW Zhang, T Inaba, M Kennedy, RT Kulkarni, RN AF Morioka, Tomoaki Dishinger, John. F. Reid, Kendra. R. Liew, Chong Wee Zhang, Ting Inaba, Masaaki Kennedy, Robert. T. Kulkarni, Rohit. N. TI Enhanced GLP-1-and Sulfonylurea-Induced Insulin Secretion in Islets Lacking Leptin Signaling SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; ACTIVATION; GLUCOSE; RAT; RECEPTOR; CHANNELS; CRI-G1; GROWTH; LINE; CAMP AB We have previously reported that the absence of leptin signaling in beta-cells enhances glucose-stimulated insulin secretion and improves glucose tolerance in vivo. To investigate the relevance of beta-cell leptin signaling in the context of postprandial or therapeutic insulin secretion, we examined the cross talk between leptin and glucagon-like peptide (GLP)-1 and sulfonylurea actions. Single and size-matched islets isolated from control or pancreas-specific leptin receptor knockout (pancreas-ObR-KO) mice were treated either with GLP-1 or with glibenclamide. Leptin suppressed GLP-1-stimulated intracellular Ca2+ concentrations ([Ca2+](i)) increase that paralleled the decrease in insulin secretion in controls. In contrast, and as expected, the ObR-KO islets were nonresponsive to leptin, and instead, showed a 2.8-fold greater GLP-1-stimulated [Ca2+](i) increase and a 1.7-fold greater insulin secretion. Phosphorylation of cAMP-responsive element binding protein was enhanced, and phosphodiesterase enzymatic activity was suppressed in MIN6 beta-cells with ObR knockdown compared with controls. The ObR-KO islets also showed significantly higher glibenclamide-induced insulin secretion compared with control islets, whereas [Ca2+](i) was similar to the controls. These data support enhanced insulinotropic effects of glucose, GLP-1, and sulfonyl-ureas in the islets lacking leptin signaling with potential therapeutic implications. (Molecular Endocrinology 26: 967-976, 2012) C1 [Morioka, Tomoaki; Liew, Chong Wee; Kulkarni, Rohit. N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Morioka, Tomoaki; Liew, Chong Wee; Kulkarni, Rohit. N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Dishinger, John. F.; Reid, Kendra. R.; Zhang, Ting; Kennedy, Robert. T.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Dishinger, John. F.; Reid, Kendra. R.; Zhang, Ting; Kennedy, Robert. T.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Morioka, Tomoaki; Inaba, Masaaki] Osaka City Univ, Grad Sch Med, Osaka 5458585, Japan. RP Kulkarni, RN (reprint author), 602 1 Joslin Pl, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu RI Kennedy, Robert/G-9095-2016 OI Kennedy, Robert/0000-0003-2447-7471 FU American Diabetes Association [7-07-RA-84]; National Institutes of Health [RO1 DK67536, 1-K99 DK090210-01]; Japanese Ministry of Education, Culture, Sports, Science and Technology [B 21790878]; The Osaka Medical Research Foundation for Incurable Diseases FX This work was supported by an American Diabetes Association Research Award (7-07-RA-84) (to R.N.K.) and in part by National Institutes of Health Grant RO1 DK67536. T.M. was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Young Scientists B 21790878) and The Osaka Medical Research Foundation for Incurable Diseases. C.W.L. is supported by National Institutes of Health Grant 1-K99 DK090210-01. NR 31 TC 5 Z9 5 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2012 VL 26 IS 6 BP 967 EP 976 DI 10.1210/me.2011-1306 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 946PM UT WOS:000304365100008 PM 22474124 ER PT J AU Hoh, BL Neal, DW Kleinhenz, DT Hoh, DJ Mocco, J Barker, FG AF Hoh, Brian L. Neal, Daniel W. Kleinhenz, Dominic T. Hoh, Daniel J. Mocco, J. Barker, Fred G., II TI Higher Complications and No Improvement in Mortality in the ACGME Resident Duty-Hour Restriction Era: An Analysis of More Than 107000 Neurosurgical Trauma Patients in the Nationwide Inpatient Sample Database SO NEUROSURGERY LA English DT Article DE Complications; Medical errors; Mortality; Neurosurgery; Residency; Training; Trauma ID STAFF WORKING HOURS; ACCREDITATION-COUNCIL; SLEEP-DEPRIVATION; INTERNAL-MEDICINE; SURGICAL RESIDENTS; HOURS REGULATIONS; IMPACT; CARE; EDUCATION; REFORM AB BACKGROUND: The Accreditation Council for Graduate Medical Education resident duty-hour restrictions were implemented in July 2003 based on the supposition that resident fatigue contributes to medical errors. OBJECTIVE: To examine the effect of duty-hour restrictions on outcome in neurotrauma patients. METHODS: The Nationwide Inpatient Sample database was analyzed for a time period with no restrictions (years 1999-2002) compared with a period with restrictions (years 2005-2008) for (1) mortality and (2) complications. We analyzed both teaching and nonteaching hospitals to account for potential differences attributed to nonresident-related factors. RESULTS: There were 107 006 teaching hospital and 115 604 nonteaching hospital admissions for neurotrauma. Multivariate logistic regression demonstrated significantly more complications in the time period with restrictions in teaching hospitals. In nonteaching hospitals, there was no difference in complications. In both teaching and nonteaching hospitals, there was no difference in mortality between the 2 time periods. For teaching and nonteaching hospitals, there was no difference in hospital length of stay, but hospital charges were significantly higher in the period with restrictions. The occurrence of a complication was significantly associated with longer hospital length of stay and higher hospital charges in both time periods in both teaching and nonteaching hospitals. CONCLUSION: The implementation of the Accreditation Council for Graduate Medical Education resident duty-hour restrictions was associated with increased complications and no change in mortality for neurotrauma patients in teaching hospitals. In nonteaching hospitals, there was no change in complications and mortality. The occurrence of a complication was associated with longer length of stay and higher hospital charges in both time periods in both teaching and nonteaching hospitals. C1 [Hoh, Brian L.; Kleinhenz, Dominic T.; Hoh, Daniel J.; Mocco, J.] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. [Neal, Daniel W.] Univ Florida, Dept Biostat, Gainesville, FL 32610 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Hoh, BL (reprint author), Univ Florida, Dept Neurosurg, POB 100265, Gainesville, FL 32610 USA. EM brian.hoh@neurosurgery.ufl.edu FU Codman Neurovascular FX Dr Mocco received an unrestricted educational grant from Codman Neurovascular and is a consultant to Actelion Pharmaceuticals, Nfocus, and Lazarus Effect. The other authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 45 TC 26 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2012 VL 70 IS 6 BP 1369 EP 1381 DI 10.1227/NEU.0b013e3182486a75 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 946RV UT WOS:000304372600020 PM 22227483 ER PT J AU Taylor, JJ Borckardt, JJ George, MS AF Taylor, Joseph J. Borckardt, Jeffrey J. George, Mark S. TI Endogenous opioids mediate left dorsolateral prefrontal cortex rTMS-induced analgesia SO PAIN LA English DT Article DE Pain modulation; Endogenous opioids; rTMS; Analgesia; Prefrontal cortex ID TRANSCRANIAL MAGNETIC STIMULATION; ROSTRAL VENTROMEDIAL MEDULLA; ANTERIOR CINGULATE CORTEX; PERIAQUEDUCTAL GRAY; HEALTHY-VOLUNTEERS; PLACEBO ANALGESIA; BRAIN-STEM; CORTICAL PROJECTIONS; PAIN THRESHOLDS; MOOD DISORDERS AB The concurrent rise of undertreated pain and opiate abuse poses a unique challenge to physicians and researchers alike. A focal, noninvasive form of brain stimulation called repetitive transcranial magnetic stimulation (rTMS) has been shown to produce acute and chronic analgesic effects when applied to dorsolateral prefrontal cortex (DLPFC), but the anatomical and pharmacological mechanisms by which prefrontal rTMS induces analgesia remain unclear. Data suggest that DLPFC mediates top-down analgesia via gain modulation of the supraspinal opioidergic circuit. This potential pathway might explain how prefrontal rTMS reduces pain. The purpose of this sham-controlled, double-blind, crossover study was to determine whether left DLPFC rTMS-induced analgesia was sensitive to l-opioid blockade. Twenty-four healthy volunteers were randomized to receive real or sham TMS after either intravenous saline or naloxone pretreatment. Acute hot and cold pain via quantitative sensory testing and hot allodynia via block testing on capsaicin-treated skin were assessed at baseline and at 0, 20, and 40 minutes after TMS treatment. When compared to sham, real rTMS reduced hot pain and hot allodynia. Naloxone pretreatment significantly reduced the analgesic effects of real rTMS. These results demonstrate that left DLPFC rTMS-induced analgesia requires opioid activity and suggest that rTMS drives endogenous opioidergic pain relief in the human brain. Further studies with chronic dosing regimens of drugs that block or augment the actions of opiates are needed to determine whether TMS can augment opiates in chronic or postoperative pain management. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Taylor, Joseph J.] Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Dept Psychiat, Charleston, SC 29414 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Taylor, JJ (reprint author), Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Dept Psychiat, 67 President St,Room 504 N, Charleston, SC 29414 USA. EM taylorjj@musc.edu FU NIDA NIH HHS [F30 DA033748] NR 72 TC 32 Z9 32 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN PY 2012 VL 153 IS 6 BP 1219 EP 1225 DI 10.1016/j.pain.2012.02.030 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 945BZ UT WOS:000304249100017 PM 22444187 ER PT J AU Briere, LC Roberts, AE Joshi, V AF Briere, Lauren C. Roberts, Amy E. Joshi, Victoria TI Correspondence regarding genetic assessment following increased nuchal translucency and normal karyotype SO PRENATAL DIAGNOSIS LA English DT Article ID NOONAN-SYNDROME; SOS1; MUTATIONS C1 [Briere, Lauren C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Roberts, Amy E.] Childrens Hosp, Boston, MA 02115 USA. [Joshi, Victoria] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Briere, LC (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM lcbriere@bidmc.harvard.edu FU European Union [037244]; Canada-Israel industrial RD Fund (CIIRDF) [39] FX This study was funded part by the European Union FP6 grant Pregenesys # 037244 (HM) and the Canada-Israel industrial R&D Fund (CIIRDF) # 39 (HM). NR 4 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD JUN PY 2012 VL 32 IS 6 BP 607 EP 608 DI 10.1002/pd.2920 PG 2 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 946XJ UT WOS:000304390500017 PM 22622833 ER PT J AU Yagi, M Murray, J Strand, K Blystone, S Interlandi, G Suda, Y Sobel, M AF Yagi, Mayumi Murray, Jacqueline Strand, Kurt Blystone, Scott Interlandi, Gianluca Suda, Yasuo Sobel, Michael TI Heparin modulates the conformation and signaling of platelet integrin alpha IIb beta 3 SO THROMBOSIS RESEARCH LA English DT Article DE Heparin; Integrin alpha IIb beta 3 (platelet glycoprotein IIbIIIa); Platelet activation; Src kinase; Surface plasmon resonance; Tyrosine phosphorylation ID PERCUTANEOUS CORONARY INTERVENTION; MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED-HEPARIN; TYROSINE PHOSPHORYLATION; BINDING DOMAIN; LIGAND-BINDING; ACTIVATION; AGGREGATION; ADHESION; IIIA AB Introduction: The glycosaminoglycan heparin has been shown to bind to platelet integrin alpha IIb beta 3 and induce platelet activation and aggregation, although the relationship between binding and activation is unclear. We analyzed the interaction of heparin and alpha IIb beta 3 in detail, to obtain a better understanding of the mechanism by which heparin acts on platelets. Methods: We assessed conformational changes in alpha IIb beta 3 by flow cytometry of platelets exposed to unfractionated heparin. In human platelets and K562 cells engineered to express alpha IIb beta 3, we assayed the effect of heparin on key steps in integrin signaling: phosphorylation of the beta 3 chain cytoplasmic tail, and activation of src kinase. We measured the heparin binding affinity of purified alpha IIb beta 3, and of recombinant fragments of alpha IIb and beta 3, by surface plasmon resonance. Results and conclusions: Heparin binding results in conformational changes in alpha IIb beta 3, similar to those observed upon ligand binding. Heparin binding alone is not sufficient to induce tyrosine phosphorylation of the integrin beta 3 cytoplasmic domain, but the presence of heparin increased both beta 3 phosphorylation and src kinase activation in response to ligand binding. Specific recombinant fragments derived from alpha IIb bound heparin, while recombinant beta 3 did not bind. This pattern of heparin binding, compared to the crystal structure of alpha IIb beta 3, suggests that heparin-binding sites are located in clusters of basic amino acids in the headpiece and/or leg domains of alpha IIb. Binding of heparin to these clusters may stabilize the transition of alpha IIb beta 3 to an open conformation with enhanced affinity for ligand, facilitating outside-in signaling and platelet activation. Published by Elsevier Ltd. C1 [Yagi, Mayumi; Murray, Jacqueline; Strand, Kurt; Sobel, Michael] VA Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Murray, Jacqueline; Sobel, Michael] Univ Washington, Dept Surg, Div Vasc Surg, Seattle, WA 98195 USA. [Blystone, Scott] SUNY Upstate Med Univ, Dept Cell & Dev Biol, Syracuse, NY USA. [Interlandi, Gianluca] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Suda, Yasuo] Kagoshima Univ, Dept Nanostruct & Adv Mat, Grad Sch Sci & Engn, Kagoshima 890, Japan. RP Yagi, M (reprint author), VA Puget Sound Hlth Care Syst, Res & Dev 151, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. EM myagi@uw.edu FU National Institutes of Health [HL39903]; Department of Veterans Affairs FX This work was supported by grants from the National Institutes of Health (HL39903) and the Department of Veterans Affairs to MS. NR 38 TC 6 Z9 6 U1 1 U2 6 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 2012 VL 129 IS 6 BP 743 EP 749 DI 10.1016/j.thromres.2011.11.054 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 945HG UT WOS:000304263100013 PM 22197178 ER PT J AU Sumorok, NT Asplin, JR Eisner, BH Stoller, ML Goldfarb, DS AF Sumorok, Nicola T. Asplin, John R. Eisner, Brian H. Stoller, Marshall L. Goldfarb, David S. TI Effect of diet orange soda on urinary lithogenicity SO UROLOGICAL RESEARCH LA English DT Article DE Alkalies; Carbonated beverages; Citrates; Nephrolithiasis; Urolithiasis ID STONE RISK; HYPOCITRATURIC NEPHROLITHIASIS; CALCIUM NEPHROLITHIASIS; LEMONADE; MANIPULATION; PARAMETERS; VOLUME; JUICE AB Studies have shown that certain beverages decrease urinary lithogenicity by increasing urine citrate excretion. Diet Sunkist Orange soda had the highest concentration of citrate and total alkali content among 12 diet sodas previously assayed. We studied the effect of Diet Sunkist Orange soda consumption on urinary chemistry. Nine healthy men and women ages 26-54 years completed the study. During the control period, subjects drank 36 oz of water for 3 days in addition to their own, self-selected diet and recorded a food diary. During the study period, the subjects drank three 12-oz cans of Diet Sunkist Orange soda a day instead of water, and replicated their diets from the control period. In each period, the subjects performed 24-h urine collections on days 2 and 3. Urine chemical analysis was performed, including urinary citrate levels and pH. Diet Sunkist Orange soda increased urinary citrate excretion by 60 mg/day, which was not statistically significant (95% CI -75 to 195, value 0.34). There was no significant change in pH from the control period to the study period (pH: 6.29-6.21; 95% CI: -0.09 to 0.25, = 0.30). Urine volumes and creatinine excretions were not significantly different between the control and study periods. Despite the relatively high citrate and total alkali content of Diet Sunkist Orange soda, the volume consumed in this study (36 oz per day) did not provide sufficient potential base to significantly alter urine composition in healthy subjects with normocitraturia. The effect of Diet Sunkist Orange soda on urinary chemistry in patients with hypocitraturia and nephrolithiasis is not likely to have a clinically significant effect to prevent calcium or uric acid stones. C1 [Goldfarb, David S.] New York Harbor VA Hlth Care Syst, Nephrol Sect 111G, New York, NY 10010 USA. [Sumorok, Nicola T.; Goldfarb, David S.] NYU, Dept Med, Langone Med Ctr, New York, NY 10016 USA. [Sumorok, Nicola T.; Goldfarb, David S.] NYU, Div Nephrol, Langone Med Ctr, New York, NY USA. [Asplin, John R.] Univ Chicago, Sch Med, Litholink Corp & Renal Sect, Chicago, IL 60637 USA. [Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Stoller, Marshall L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. RP Goldfarb, DS (reprint author), New York Harbor VA Hlth Care Syst, Nephrol Sect 111G, E 23 St, New York, NY 10010 USA. EM david.goldfarb@va.gov OI Goldfarb, David/0000-0002-9215-1273 NR 18 TC 6 Z9 6 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0300-5623 J9 UROL RES JI Urol. Res. PD JUN PY 2012 VL 40 IS 3 BP 237 EP 241 DI 10.1007/s00240-011-0418-2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 944MT UT WOS:000304208200008 PM 21858427 ER PT J AU Aspinall, SL Smith, KJ Good, CB Zhao, X Stone, RA Tonnu-Mihara, IQ Cunningham, FE AF Aspinall, S. L. Smith, K. J. Good, C. B. Zhao, X. Stone, R. A. Tonnu-Mihara, I. Q. Cunningham, F. E. TI INCREMENTAL COST-EFFECTIVENESS OF PHARMACIST-MANAGED ERYTHROPOIESIS-STIMULATING AGENTS CLINICS FOR NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Aspinall, S. L.; Good, C. B.; Cunningham, F. E.] VA Ctr Medicat Safety, Hines, IL USA. [Smith, K. J.; Stone, R. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Zhao, X.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Tonnu-Mihara, I. Q.] VA Long Beach Healthcare Syst, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A155 EP A156 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200806 ER PT J AU Choi, S Neuwirth, R Cakana, A San Miguel, JF Richardson, PG AF Choi, S. Neuwirth, R. Cakana, A. San Miguel, J. F. Richardson, P. G. TI PATIENT-REPORTED OUTCOME (PRO) INSTRUMENT FOR DETECTION OF PERIPHERAL NEUROPATHY (PN) IN PATIENTS WITH MULTIPLE MYELOMA (MM): THE FACT/GOG-NTX SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Choi, S.; Neuwirth, R.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Cakana, A.] Janssen Cilag Pty Ltd, High Wycombe, Bucks, England. [San Miguel, J. F.] Hosp Univ Salamanca, CIC, IBMCC USAL CSIC, Salamanca, Spain. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A106 EP A106 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200548 ER PT J AU Forrest, G Larson, K Crompton, M Patel, H Boening, AJ AF Forrest, G. Larson, K. Crompton, M. Patel, H. Boening, A. J. TI HEALTH OUTCOMES WITH DAPTOMYCIN (DAP) IN THE TREATMENT OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS BACTEREMIA (MRSA-B) WITH VANCOMYCIN (VAN) MINIMUM INHIBITORY CONCENTRATION (MIC)=2 mu G/Ml SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Forrest, G.] OHSU, Portland, OR USA. [Forrest, G.] Portland VA Med Ctr, Portland, OR USA. [Larson, K.; Crompton, M.; Patel, H.; Boening, A. J.] Cubist Pharmaceut Inc, Lexington, MA USA. NR 0 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 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A237 EP A237 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468201425 ER PT J AU Ganapathy, V Hay, JW Smoot, KJ Lawler, E Weber, HC Grotzinger, KM AF Ganapathy, V Hay, J. W. Smoot, K. J. Lawler, E. Weber, H. C. Grotzinger, K. M. TI RESOURCE UTILIZATION IN THROMBOCYTOPENIA OF CHRONIC LIVER DISEASES IN THE VETERANS AFFAIRS POPULATION SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Ganapathy, V; Hay, J. W.] Univ So Calif, Los Angeles, CA USA. [Smoot, K. J.; Lawler, E.] Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Weber, H. C.] VA Boston Healthcare Syst, Boston, MA USA. [Grotzinger, K. M.] SmithKline Beecham Pharmaceut, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A137 EP A137 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200710 ER PT J AU Hatoum, IJ Hunter, TD Francis, DM Steinbuch, M Kaplan, LM AF Hatoum, I. J. Hunter, T. D. Francis, D. M. Steinbuch, M. Kaplan, L. M. TI IDENTIFICATION OF BARIATRIC SURGICAL PROCEDURES, COMORBIDITIES AND ADVERSE EVENTS IN PAYOR DATA SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Hatoum, I. J.; Kaplan, L. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hunter, T. D.] S2 Stat Solut Inc, Cincinnati, OH USA. [Francis, D. M.] Ethicon Endosurg Inc, Cincinnati, OH USA. [Steinbuch, M.] Johnson & Johnson, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A80 EP A80 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200417 ER PT J AU Landsman-Blumberg, P Wei, W Douglas, D Smith, DM Camargo, CA AF Landsman-Blumberg, P. Wei, W. Douglas, D. Smith, D. M. Camargo, C. A. TI A LARGE-SCALE RETROSPECTIVE STUDY OF EMERGENCY DEPARTMENT VISITS OR HOSPITALIZATIONS FOR ANAPHYLAXIS AMONG PATIENTS WITH EMPLOYER-SPONSORED HEALTH INSURANCE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Landsman-Blumberg, P.; Smith, D. M.] Thomson Reuters, Washington, DC USA. [Wei, W.] Sanofi Aventis, Bridgewater, NJ USA. [Douglas, D.] Rutgers State Univ, Ernest Mario Sch Pharm, Piscataway, NJ USA. [Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A60 EP A60 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200307 ER PT J AU Romley, J Jena, A Goldman, D AF Romley, J. Jena, A. Goldman, D. TI HOSPITAL SPENDING AND INPATIENT MORTALITY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Romley, J.; Goldman, D.] Univ So Calif, Los Angeles, CA USA. [Jena, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A20 EP A20 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200100 ER PT J AU Sansgiry, S Naik, AD Brown, AC Latini, DM AF Sansgiry, S. Naik, A. D. Brown, A. C. Latini, D. M. TI VARIATION IN ATTACHMENT STYLE AND HEALTH OUTCOMES OF DIABETES PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Sansgiry, S.; Naik, A. D.] Baylor Coll Med, VA HSR&D Ctr Excellence, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Latini, D. M.] San Francisco VA Med Ctr, Baylor Coll Med, Scott Dept Urol, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A184 EP A185 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468201151 ER PT J AU Spiegel, B Poysophon, P Snyder, B Agarwal, N Yen, L Hodgkins, P Cohen, E Vu, M Kurzbard, N Atia, M Sheen, V Kaneshiro, M Fuller, G Bolus, R AF Spiegel, B. Poysophon, P. Snyder, B. Agarwal, N. Yen, L. Hodgkins, P. Cohen, E. Vu, M. Kurzbard, N. Atia, M. Sheen, V Kaneshiro, M. Fuller, G. Bolus, R. TI RESOURCE UTILIZATION AND COSTS ASSOCIATED WITH DIVERTICULITIS INPATIENT ADMISSIONS: AN ANALYSIS OF THE ECONOMIC BURDEN OF DIVERTICULITIS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Spiegel, B.; Poysophon, P.; Snyder, B.; Agarwal, N.; Cohen, E.; Vu, M.; Kurzbard, N.; Atia, M.; Sheen, V; Kaneshiro, M.; Fuller, G.; Bolus, R.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90048 USA. [Yen, L.; Hodgkins, P.] Shire Dev LLC, Wayne, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A139 EP A139 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468200722 ER PT J AU Zhang, B Cella, DF Durie, BG Kuter, D Moreau, P Bartlett, JB Kroog, GS Wagner, S AF Zhang, B. Cella, D. F. Durie, B. G. Kuter, D. Moreau, P. Bartlett, J. B. Kroog, G. S. Wagner, S. TI DESIGN AND RATIONALE OF THE MULTIPLE MYELOMA PREAMBLE STUDY: A PROSPECTIVE, NON-INTERVENTIONAL, MULTI-CENTER COHORT STUDY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Zhang, B.] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Cella, D. F.] Northwestern Univ, Chicago, IL 60611 USA. [Durie, B. G.] IMF, Los Angeles, CA USA. [Durie, B. G.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. [Kuter, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. [Bartlett, J. B.; Kroog, G. S.; Wagner, S.] Bristol Myers Squibb Co, Princeton, NJ USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2012 VL 15 IS 4 BP A210 EP A210 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 947XP UT WOS:000304468201284 ER PT J AU Hong, SC Holbrook, EH Leopold, DA Hummel, T AF Hong, Seok-Chan Holbrook, Eric H. Leopold, Donald A. Hummel, Thomas TI Distorted olfactory perception: A systematic review SO ACTA OTO-LARYNGOLOGICA LA English DT Review DE Olfactory nerve diseases; olfaction disorders; smell ID UPPER RESPIRATORY-TRACT; TERM FOLLOW-UP; BULB VOLUME; DYSFUNCTION; PAROSMIA; SMELL; TRANSECTION; PHANTOSMIA; INFECTION; DISORDERS AB The sense of smell provides people with valuable input from the chemical environment around them. The human sense of smell generally fails in three ways; one is an intensity reduction and the other two are the quality of changes. Smell disorders can be classified into central or peripheral depending on their origin. Central causes can be related to an area of hyper-functioning brain cells generating this odor perception, thus olfactory distortions have also been observed with epilepsy and migraine. In this paper, we present a review of the current clinical understanding of olfactory distortions and discuss how they can be evaluated and therapies to treat this debilitating condition. C1 [Hong, Seok-Chan] Konkuk Univ Hosp, Dept Otorhinolaryngol, Seoul 412, South Korea. [Holbrook, Eric H.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Leopold, Donald A.] Univ Nebraska Med Ctr, Dept Otolaryngol Head & Neck Surg, Omaha, NE USA. [Hummel, Thomas] Univ Dresden, Dept Otorhinolaryngol, Sch Med, Dresden, Germany. RP Hong, SC (reprint author), Konkuk Univ Hosp, Dept Otorhinolaryngol, Seoul 412, South Korea. EM 20050692@kuh.ac.kr FU Konkuk University FX This work was supported by the Konkuk University. NR 27 TC 12 Z9 12 U1 2 U2 19 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JUN PY 2012 VL 132 SU 1 BP S27 EP S31 DI 10.3109/00016489.2012.659759 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 943FT UT WOS:000304106600005 PM 22582778 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI Selective, Isolated Proximal Tubular Angiotensinogen Overexpression and Salt-Sensitive Hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Editorial Material ID NEPHRON; SYSTEM C1 [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jingelfinger@partners.org NR 5 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2012 VL 25 IS 6 BP 628 EP 628 DI 10.1038/ajh.2012.23 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 944GZ UT WOS:000304188600001 PM 22592314 ER PT J AU Dong, F Wang, CF Farris, AB Wu, SL Lee, H Olumi, AF McDougal, WS Young, RH Wu, CL AF Dong, Fei Wang, Chaofu Farris, A. Brad Wu, Shulin Lee, Hang Olumi, Aria F. McDougal, W. Scott Young, Robert H. Wu, Chin-Lee TI Impact on the Clinical Outcome of Prostate Cancer by the 2005 International Society of Urological Pathology Modified Gleason Grading System SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Gleason score; grading; prostate cancer; prognosis; classification ID RADICAL PROSTATECTOMY; CONSENSUS CONFERENCE; CARCINOMA; STAGE; SPECIMENS; BIOPSY; SCORE; TIME AB The 2005 International Society of Urological Pathology (ISUP) Consensus Conference modified the Gleason grading system for prostate cancer. In the modified criteria, ill-defined glands with poorly formed lumina and large cribriform glands with smooth borders, classically described as Gleason pattern 3 adenocarcinoma, were redefined as Gleason pattern 4. To evaluate the clinical outcome of patients upgraded by the ISUP criteria, the histologic slides of 1240 consecutive radical prostatectomy specimens at a single institution were reviewed, and each case of adenocarcinoma was graded on the basis of the original and modified Gleason criteria. A total of 806 patients with prostate cancer of classical Gleason score 3 + 3 = 6 or 3 + 4 = 7 and modified Gleason score 6 to 8 were analyzed with a median overall follow-up of 12.6 years. In the study population, 34% of patients with classical Gleason score 3 + 3 = 6 prostate cancer were upgraded to modified Gleason score 7 or 8 by the ISUP criteria. Compared to patients with modified Gleason score 3 + 3 = 6 and patients with classical Gleason score 3 + 4 = 7, the upgraded patients were at intermediate risk for biochemical progression (paired log-rank P <= 0.003) and metastasis (paired log-rank P <= 0.04) after radical prostatectomy. The hazard ratio for upgrading was 1.60 (95% confidence interval, 1.09-2.35, P = 0.02) for biochemical recurrence and 5.02 (95% confidence interval, 1.77-14.2, P = 0.003) for metastasis. These results validate the prognostic value of the modified Gleason grading system and suggest that the recognition of an intermediate-risk histological pattern may be useful in the prognosis of patients with prostate cancer. C1 [Dong, Fei; Wang, Chaofu; Farris, A. Brad; Wu, Shulin; Young, Robert H.; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Olumi, Aria F.; McDougal, W. Scott; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Wu, CL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM cwu2@partners.org NR 21 TC 42 Z9 47 U1 0 U2 4 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 2012 VL 36 IS 6 BP 838 EP 843 DI 10.1097/PAS.0b013e3182486faf PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 944KP UT WOS:000304200700006 PM 22592143 ER PT J AU Yamato, M Ketten, DR Arruda, J Cramer, S Moore, K AF Yamato, Maya Ketten, Darlene R. Arruda, Julie Cramer, Scott Moore, Kathleen TI The Auditory Anatomy of the Minke Whale (Balaenoptera acutorostrata): A Potential Fatty Sound Reception Pathway in a Baleen Whale SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE cetacea; mysticete; hearing; ear; acoustic fat; imaging ID TURSIOPS-TRUNCATUS; HEARING; DOLPHIN; TRANSMISSION; SENSITIVITY; TISSUES; LIPIDS; JAW AB Cetaceans possess highly derived auditory systems adapted for underwater hearing. Odontoceti (toothed whales) are thought to receive sound through specialized fat bodies that contact the tympanoperiotic complex, the bones housing the middle and inner ears. However, sound reception pathways remain unknown in Mysticeti (baleen whales), which have very different cranial anatomies compared to odontocetes. Here, we report a potential fatty sound reception pathway in the minke whale (Balaenoptera acutorostrata), a mysticete of the balaenopterid family. The cephalic anatomy of seven minke whales was investigated using computerized tomography and magnetic resonance imaging, verified through dissections. Findings include a large, well-formed fat body lateral, dorsal, and posterior to the mandibular ramus and lateral to the tympanoperiotic complex. This fat body inserts into the tympanoperiotic complex at the lateral aperture between the tympanic and periotic bones and is in contact with the ossicles. There is also a second, smaller body of fat found within the tympanic bone, which contacts the ossicles as well. This is the first analysis of these fatty tissues' association with the auditory structures in a mysticete, providing anatomical evidence that fatty sound reception pathways may not be a unique feature of odontocete cetaceans. Anat Rec, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Yamato, Maya; Ketten, Darlene R.; Arruda, Julie; Cramer, Scott] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Ketten, Darlene R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Arruda, Julie] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Moore, Kathleen] Int Fund Anim Welf Marine Mammal Rescue & Res, Yarmouth Port, MA USA. RP Yamato, M (reprint author), Woods Hole Oceanog Inst, Dept Biol, 266 Woods Hole Rd,MS 50, Woods Hole, MA 02543 USA. EM myamato@whoi.edu FU National Science Foundation; Ocean Life Institute; WHOI; Princeton University Ecology and Evolutionary Biology Department; Joint Industry Program; Office of Naval Research; Naval Operations Energy and Environmental Readiness Division FX Grant sponsors: National Science Foundation Graduate Research Fellowship, Ocean Life Institute Graduate Fellowship, WHOI Summer Student Fellowship, WHOI Minority Fellowship, Princeton University Ecology and Evolutionary Biology Department Senior Thesis Fund, Joint Industry Program, Office of Naval Research Marine Mammal Program, Chief of Naval Operations Energy and Environmental Readiness Division. NR 43 TC 20 Z9 20 U1 0 U2 48 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1932-8486 J9 ANAT REC JI Anat. Rec. PD JUN PY 2012 VL 295 IS 6 BP 991 EP 998 DI 10.1002/ar.22459 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA 940SY UT WOS:000303914600012 PM 22488847 ER PT J AU Conrad, C Konuk, Y Werner, PD Cao, CG Warshaw, AL Rattner, DW Stangenberg, L Ott, HC Jones, DB Miller, DL Gee, DW AF Conrad, Claudius Konuk, Yusuf Werner, Paul D. Cao, Caroline G. Warshaw, Andrew L. Rattner, David W. Stangenberg, Lars Ott, Harald C. Jones, Daniel B. Miller, Diane L. Gee, Denise W. TI A Quality Improvement Study on Avoidable Stressors and Countermeasures Affecting Surgical Motor Performance and Learning SO ANNALS OF SURGERY LA English DT Article ID LAPAROSCOPIC TASK; MUSIC EXPERIENCE; NOISE; SURGEONS AB Objective: To explore how the 2 most important components of surgical performance-speed and accuracy-are influenced by different forms of stress and what the impact of music is on these factors. Background: On the basis of a recently published pilot study on surgical experts, we designed an experiment examining the effects of auditory stress, mental stress, and music on surgical performance and learning and then correlated the data psychometric measures to the role of music in a novice surgeon's life. Methods: Thirty-one surgeons were recruited for a crossover study. Surgeons were randomized to 4 simple standardized tasks to be performed on the SurgicalSIM VR laparoscopic simulator (Medical Education Technologies, Inc, Sarasota, FL), allowing exact tracking of speed and accuracy. Tasks were performed under a variety of conditions, including silence, dichotic music (auditory stress), defined classical music (auditory relaxation), and mental loading (mental arithmetic tasks). Tasks were performed twice to test for memory consolidation and to accommodate for baseline variability. Performance was correlated to the brief Musical Experience Questionnaire (MEQ). Results: Mental loading influences performance with respect to accuracy, speed, and recall more negatively than does auditory stress. Defined classical music might lead to minimally worse performance initially but leads to significantly improved memory consolidation. Furthermore, psychologic testing of the volunteers suggests that surgeons with greater musical commitment, measured by the MEQ, perform worse under the mental loading condition. Conclusions: Mental distraction and auditory stress negatively affect specific components of surgical learning and performance. If used appropriately, classical music may positively affect surgical memory consolidation. It also may be possible to predict surgeons' performance and learning under stress through psychological tests on the role of music in a surgeon's life. Further investigation is necessary to determine the cognitive processes behind these correlations. C1 [Conrad, Claudius; Jones, Daniel B.] Harvard Univ, Sch Med, Dept Surg, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Conrad, Claudius; Konuk, Yusuf; Warshaw, Andrew L.; Rattner, David W.; Stangenberg, Lars; Ott, Harald C.; Gee, Denise W.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Werner, Paul D.] Alliant Int Univ, Calif Sch Profess Psychol, San Francisco, CA USA. [Cao, Caroline G.] Tufts Univ, Dept Mech Engn, Medford, MA 02155 USA. [Miller, Diane L.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Conrad, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Beth Israel Deaconess Med Ctr, 55 Fruit St, Boston, MA 02114 USA. EM Cconrad1@partners.org FU NIBIB NIH HHS [R01 EB005807, R01 EB009362, R01 EB010037, R01 EB010037-01, R01 EB010037-02, R01 EB010037-03, R01 EB014305] NR 24 TC 10 Z9 10 U1 1 U2 15 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 2012 VL 255 IS 6 BP 1190 EP 1194 DI 10.1097/SLA.0b013e318250b332 PG 5 WC Surgery SC Surgery GA 943DQ UT WOS:000304101100037 PM 22584632 ER PT J AU Fung, TT Hu, FB Schulze, M Pollak, M Wu, TY Fuchs, CS Giovannucci, E AF Fung, Teresa T. Hu, Frank B. Schulze, Matthias Pollak, Michael Wu, Tianying Fuchs, Charles S. Giovannucci, Edward TI A dietary pattern that is associated with C-peptide and risk of colorectal cancer in women SO CANCER CAUSES & CONTROL LA English DT Article DE Colorectal cancer; Diet; C-peptide ID FOOD-FREQUENCY QUESTIONNAIRE; GROWTH-FACTOR-I; CARDIOVASCULAR-DISEASE; DECAFFEINATED COFFEE; BINDING-PROTEINS; INSULIN INDEX; LOAD; REPRODUCIBILITY; BIOMARKERS; VALIDITY AB Higher serum C-peptide concentrations have shown to be associated with an increased risk of colorectal cancer (CRC). Therefore, we used diet information to identify food groups that correlated with fasting serum concentrations of C-peptide and assess the association of this dietary pattern and CRC risk. Major food contributors to fasting C-peptide concentrations were identified with stepwise linear regression in a subsample ( = 833) of women from a large cohort. We then summed the consumption frequency of the major food contributors to form a C-peptide dietary pattern for the entire cohort ( = 66,714). Risk for CRC was computed using Cox proportional hazard model with the C-peptide dietary pattern score as the predictor. In up to 20 years of follow-up, we ascertained 985 cases of CRC and 758 colon cancer. After adjusting for confounders, the C-peptide dietary pattern, characterized by higher meat, fish, and sweetened beverage intake, but lower coffee, high fat dairy, and whole grains intake, showed direct association with CRC risk (RR comparing extreme quintiles = 1.29, 95 % CI = 1.05-1.58, trend = 0.048). The same comparison was slightly stronger for colon cancer (RR = 1.35, 95 % CI = 1.07-1.70, trend = 0.009). In stratified analysis, there was no association between the C-peptide dietary pattern and colon cancer among lean and active women. However, for overweight or sedentary women, RR for the same comparison was 1.58 (95 % CI = 1.20-2.07, trend = 0.002) ( for interaction = 0.007). We derived a dietary pattern that correlated with C-peptide concentrations. This pattern was associated with an increase in colon cancer, especially among women who were overweight or sedentary. C1 [Fung, Teresa T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. [Fung, Teresa T.; Hu, Frank B.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hu, Frank B.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA. [Schulze, Matthias] Tech Univ Munich, Munich, Germany. [Schulze, Matthias] German Inst Human Nutr, Munich, Germany. [Pollak, Michael] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ, Canada. [Wu, Tianying] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Fung, TT (reprint author), Simmons Coll, Dept Nutr, 300 Fenway, Boston, MA 02115 USA. EM fung@simmons.edu RI Pollak, Michael/G-9094-2011; OI Pollak, Michael/0000-0003-3047-0604; Yang, Shuman/0000-0002-9638-0890; Schulze, Matthias B./0000-0002-0830-5277 FU National Institute of Health [CA87969, HL60712, CA95589] FX We would like to thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as 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 is funded by the National Institute of Health research grants CA87969, HL60712, and CA95589. NR 26 TC 9 Z9 9 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2012 VL 23 IS 6 BP 959 EP 965 DI 10.1007/s10552-012-9969-y PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 943FK UT WOS:000304105700017 PM 22535146 ER PT J AU Lanternier, F Sun, HY Ribaud, P Singh, N Kontoyiannis, DP Lortholary, O AF Lanternier, Fanny Sun, Hsin-Yun Ribaud, Patricia Singh, Nina Kontoyiannis, Dimitrios P. Lortholary, Olivier TI Mucormycosis in Organ and Stem Cell Transplant Recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; SURVEILLANCE NETWORK TRANSNET; MOLD INFECTIONS; HEMATOLOGIC MALIGNANCY; ANTIFUNGAL THERAPY; MURINE ZYGOMYCOSIS; RHIZOPUS-ORYZAE; IRON OVERLOAD; RISK-FACTORS AB Mucormycosis is a devastating invasive fungal disease whose incidence has increased during the past decade. Mucormycosis now represents a major threat in transplant recipients, accounting for 2% and 8% of invasive fungal infections in recent cohorts of solid-organ and allogeneic stem-cell transplant recipients, respectively. Mucormycosis most often occurs late, >3 months after transplantation, although cases occurring early have been observed, especially among liver transplant recipients and in cases of graft-transmitted infection. Recent guidelines have emphasized the direct examination of the involved fluid or tissue and culture from a sterile site as the most appropriate diagnostic strategy and the use of lipid formulations of amphotericin B and major surgery when feasible as the most appropriate first-line therapeutic strategy for mucormycosis in organ and stem cell transplant recipients. C1 [Lanternier, Fanny; Lortholary, Olivier] Univ Paris 05, Hop Necker Enfants Malad, Ctr Infect Necker Pasteur, F-75105 Paris, France. [Lanternier, Fanny; Lortholary, Olivier] IHU Imagine, Paris, France. [Lanternier, Fanny; Lortholary, Olivier] Ctr Natl Reference Mycol & Antifong, Inst Pasteur, Paris, France. [Lortholary, Olivier] CNRS, URA 3012, Paris, France. [Sun, Hsin-Yun; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Sun, Hsin-Yun; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Ribaud, Patricia] Univ Paris 07, UFR Denis Diderot, F-75221 Paris 05, France. [Ribaud, Patricia] Hop St Louis, Assistance Publ Hop Paris, Serv Hematol Greffe Moelle, Paris, France. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. RP Lortholary, O (reprint author), Univ Paris 05, Hop Necker Enfants Malad, Ctr Infect Necker Pasteur, 149 Rue Sevres, F-75105 Paris, France. EM olivier.lortholary@nck.aphp.fr OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 62 TC 37 Z9 39 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2012 VL 54 IS 11 BP 1629 EP 1636 DI 10.1093/cid/cis195 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942MO UT WOS:000304048400020 PM 22431807 ER PT J AU Stanley, TL Falutz, J Marsolais, C Morin, J Soulban, G Mamputu, JC Assaad, H Turner, R Grinspoon, SK AF Stanley, Takara L. Falutz, Julian Marsolais, Christian Morin, Josee Soulban, Graziella Mamputu, Jean-Claude Assaad, Hani Turner, Ralph Grinspoon, Steven K. TI Reduction in Visceral Adiposity Is Associated With an Improved Metabolic Profile in HIV-Infected Patients Receiving Tesamorelin SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GROWTH-HORMONE TREATMENT; ABDOMINAL FAT ACCUMULATION; PLACEBO-CONTROLLED TRIAL; BODY-COMPOSITION; REDISTRIBUTION-SYNDROME; INSULIN-RESISTANCE; SAFETY EXTENSION; FACTOR ANALOG; TISSUE; LIPODYSTROPHY AB Background. Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes. Methods. In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of 402 subjects initially randomly assigned to receive tesamorelin, those with >= 8% reduction in VAT were defined a priori as responders per the statistical analysis plan. Post hoc analyses were performed to assess differences between responders and nonresponders. Results. Compared with tesamorelin nonresponders, responders experienced greater mean (+/- SD) reduction in triglyceride levels (26 weeks: -0.6 +/- 1.7 mmol/L vs -0.1 +/- 1.2 mmol/L [P = .005]; 52 weeks: -0.8 +/- 1.8 mmol/L vs 0.0 +/- 1.1 mmol/L [P = .003]) and attenuated changes in fasting glucose levels (26 weeks: 1 +/- 16 mg/dL vs 5 +/- 14 mg/dL [P = .01]; 52 weeks: -1 +/- 14 mg/dL vs 8 +/- 17 mg/dL [P < .001]), hemoglobin A1c levels (26 weeks: 0.1 +/- 0.3% vs 0.3 +/- 0.4% [P < .001]; 52 weeks: 0.0 +/- 0.3% vs 0.2 +/- 0.5% [P = .003]), and other parameters of glucose homeostasis. Similar patterns were seen for adiponectin levels, with significant improvement in responders vs nonresponders. Changes in lipid levels and glucose homeostasis were significantly associated with percentage change in VAT. Conclusions. In contrast to nonresponders, HIV-infected patients receiving tesamorelin with >= 8% reduction in VAT have significantly improved triglyceride levels, adiponectin levels, and preservation of glucose homeostasis over 52 weeks of treatment. Clinicaltrials.gov Registration. NCT00123253, NCT00435136, NCT00608023. C1 [Stanley, Takara L.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Stanley, Takara L.; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA USA. [Falutz, Julian] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Marsolais, Christian; Morin, Josee; Soulban, Graziella; Mamputu, Jean-Claude; Assaad, Hani] Theratechnol, Montreal, PQ, Canada. [Turner, Ralph] Phase Technol 5, Wellesley, MA USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 5 Longfellow Pl,Ste 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org OI Mamputu, Jean-Claude/0000-0001-8493-959X FU Theratechnologies; National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health [K23 DK089910, K24 DK064545] FX This work was supported by Theratechnologies and by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (grant K23 DK089910 to T. L. S. and grant K24 DK064545 to S. K. G.). NR 34 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2012 VL 54 IS 11 BP 1642 EP 1651 DI 10.1093/cid/cis251 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942MO UT WOS:000304048400022 PM 22495074 ER PT J AU Musher, DM Stager, C AF Musher, Daniel M. Stager, Charles TI Diagnosis of Clostridium difficile Infection SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Musher, Daniel M.] Baylor Coll Med, Houston, TX 77030 USA. [Stager, Charles] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Lab Serv Care Line, Infect Dis Sect, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Stager, Charles] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Baylor Coll Med, Houston, TX 77030 USA. EM dmusher@bcm.edu NR 4 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2012 VL 54 IS 11 BP 1675 EP 1675 DI 10.1093/cid/cis259 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942MO UT WOS:000304048400027 PM 22503848 ER PT J AU Bedair, H Ting, N Bozic, KJ Della Valle, CJ Sporer, SM AF Bedair, Hany Ting, Nicholas Bozic, Kevin J. Della Valle, Craig J. Sporer, Scott M. TI Reply to Letter to the Editor: Treatment of Early Postoperative Infections After THA: A Decision Analysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Letter C1 [Bedair, Hany] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Ting, Nicholas; Della Valle, Craig J.; Sporer, Scott M.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Dept Orthopaed Surg, Philip R Lee Inst Hlth Policy, San Francisco, CA USA. RP Bedair, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St,YAW 3B, Boston, MA 02114 USA. EM hbedair@gmail.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 2012 VL 470 IS 6 BP 1793 EP 1794 DI 10.1007/s11999-012-2360-1 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 943BG UT WOS:000304094800039 ER PT J AU Borrero, S Mor, MK Zhao, XH McNeil, M Ibrahim, S Hayes, P AF Borrero, Sonya Mor, Maria K. Zhao, Xinhua McNeil, Melissa Ibrahim, Said Hayes, Patricia TI Contraceptive care in the VA health care system SO CONTRACEPTION LA English DT Article DE VA; Women's health; Contraception; Race/ethnicity ID OF-VETERANS-AFFAIRS; INTRAUTERINE-DEVICE; WOMEN VETERANS; DELIVERY; AVAILABILITY; ORGANIZATION; PHYSICIANS; INNOVATION; KNOWLEDGE; ATTITUDES AB Background: Little is known about contraceptive care within the Veterans Affairs (VA) health care system. This study was conducted to assess the prevalence of documented contraception by race/ethnicity within the VA and to examine the association between receiving primary care in women's health clinics (WHCs) and having a documented contraceptive method. Study Design: We examined national VA administrative and pharmacy data for 103,950 female veterans aged 18-45 years who made at least one primary care clinic visit in 2008. Multivariable regression models were used to examine the associations between race/ethnicity and receipt of care in a WHC with having a method of contraception while controlling for confounders. Results: Only 22% of women veterans had a documented method of contraception during 2008. After adjusting for potential confounders, Hispanic and African-American women were significantly less likely to have a method compared to whites [odds ratio (OR): 0.82; 95% confidence interval (CI): 0.76-0.88 and OR: 0.85; 95% CI: 0.81-0.89, respectively]. Women who went to WHCs were significantly more likely to have a method of contraception compared to women who went to traditional primary care clinics (OR: 2.05; 95% CI: 1.97-2.14). Conclusions: Overall contraceptive prevalence in the VA is low, but receiving care in a WHC is associated with a significantly higher likelihood of having a contraceptive method. Published by Elsevier Inc. C1 [Borrero, Sonya; Mor, Maria K.; Zhao, Xinhua] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Borrero, Sonya; McNeil, Melissa] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Ibrahim, Said] Philadelphia Vet Adm, Med Ctr, Philadelphia, PA 19104 USA. [Ibrahim, Said] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Hayes, Patricia] US Dept Vet Affairs, Women Vet Hlth Strateg Hlth Care Grp, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. RP Borrero, S (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM borrerosp@upmc.edu FU Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, VISN 4 CHERP FX This study was supported by the Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, VISN 4 CHERP Pilot Project Award (PI: Sonya Borrero). Dr. Borrero had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. The abstract of this manuscript was presented at The Society of General Internal Medicine annual meeting in Phoenix, AZ, in May 2011. NR 20 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JUN PY 2012 VL 85 IS 6 BP 580 EP 588 DI 10.1016/j.contraception.2011.10.010 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 944FP UT WOS:000304185000009 PM 22176794 ER PT J AU Cecere, LM Slatore, CG Uman, JE Evans, LE Udris, EM Bryson, CL Au, DH AF Cecere, Laura M. Slatore, Christopher G. Uman, Jane E. Evans, Laura E. Udris, Edmunds M. Bryson, Chris L. Au, David H. TI Adherence to Long-Acting Inhaled Therapies among Patients with Chronic Obstructive Pulmonary Disease (COPD) SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE Medication adherence; Pulmonary diseases; Chronic disease; Pharmacoepidemiology ID CLINICAL-TRIAL; MEDICATION NONADHERENCE; ASTHMATIC-PATIENTS; CORTICOSTEROIDS; MANAGEMENT; BELIEFS; PERSISTENCE; VALIDATION; CHILDREN; UNDERUSE AB Background: Long-acting inhaled medications are an important component of the treatment of patients with chronic obstructive pulmonary disease (COPD), yet few studies have examined the determinants of medication adherence among this patient population. Objective: We sought to identify factors associated with adherence to long-acting beta-agonists (LABA) and inhaled corticosteroids (ICS) among patients with COPD. Methods: We performed secondary analysis of baseline data collected in a randomized trial of 376 Veterans with spirometrically confirmed COPD. We used electronic pharmacy records to assess adherence, defined as a medication possession ratio of >= 0.80. We investigated the following exposures: patient characteristics, disease severity, medication regimen complexity, health behaviors, confidence in self-management, and perceptions of provider skill. We performed multivariable logistic regression, clustered by provider, to estimate associations. Results: Of the 167 patients prescribed LABA, 54% (n = 90) were adherent to therapy while only 40% (n = 74) of 184 the patients prescribed ICS were adherent. Higher adherence to LABA and ICS was associated with patient perception of their provider as being an "expert" in diagnosing and managing lung disease [For LABA: OR = 21.70 (95% CI 6.79, 69.37); For ICS OR = 7.93 (95% CI 1.71, 36.67)]. Factors associated with adherence to LABA, but not ICS, included: age, education, race, COPD severity, smoking status, and confidence in self-management. Conclusions: Adherence to long-acting inhaled medications among patients with COPD is poor, and determinants of adherence likely differ by medication class. Patient perception of clinician expertise in lung disease was the factor most highly associated with adherence to long-acting therapies. C1 [Cecere, Laura M.; Uman, Jane E.; Udris, Edmunds M.; Bryson, Chris L.; Au, David H.] Dept Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Cecere, Laura M.; Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Slatore, Christopher G.] Dept Vet Affairs Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Evans, Laura E.] NYU, Med Ctr, Div Pulm & Crit Care Med, Dept Med, New York, NY 10016 USA. RP Cecere, LM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lcecere@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 FU VA Advanced Fellowship Program in Health Services Research and Development [TPM 61-037]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [IIR 02-292]; Portland VA Medical Center, Portland, OR; Firland Foundation FX This material is based upon work supported by a VA Advanced Fellowship Program in Health Services Research and Development [TPM 61-037] and a Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development grant [IIR 02-292]. Dr. Slatore is supported by a Veterans Affairs HSR&D Career Development Award and resources from the Portland VA Medical Center, Portland, OR. Additional support also comes from the Firland Foundation. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. Some of the results of this work were presented in abstract form at the American Thoracic Society International Conference, in Denver, Colorado on May 15, 2011. NR 35 TC 23 Z9 23 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD JUN PY 2012 VL 9 IS 3 BP 251 EP 258 DI 10.3109/15412555.2011.650241 PG 8 WC Respiratory System SC Respiratory System GA 942ZM UT WOS:000304090200008 PM 22497533 ER PT J AU Tamura, RE de Vasconcellos, JF Sarkar, D Libermann, TA Fisher, PB Zerbini, LF AF Tamura, R. E. de Vasconcellos, J. F. Sarkar, D. Libermann, T. A. Fisher, P. B. Zerbini, L. F. TI GADD45 Proteins: Central Players in Tumorigenesis SO CURRENT MOLECULAR MEDICINE LA English DT Review DE Apoptosis; cancer; GADD45 family; survival ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; CELL-CYCLE ARREST; HISTONE DEACETYLASE INHIBITOR; DNA-DAMAGING AGENTS; HUMAN BREAST-CANCER; EXPRESSING MDA-7/IL-24-MEDIATED APOPTOSIS; NONSTEROIDAL ANTIINFLAMMATORY AGENTS; DIFFERENTIATION-ASSOCIATED GENE; VASCULAR-PERMEABILITY FACTOR AB The Growth Arrest and DNA Damage-inducible 45 (GADD45) proteins have been implicated in regulation of many cellular functions including DNA repair, cell cycle control, senescence and genotoxic stress. However, the pro-apoptotic activities have also positioned GADD45 as an essential player in oncogenesis. Emerging functional evidence implies that GADD45 proteins serve as tumor suppressors in response to diverse stimuli, connecting multiple cell signaling modules. Defects in the GADD45 pathway can be related to the initiation and progression of malignancies. Moreover, induction of GADD45 expression is an essential step for mediating anti-cancer activity of multiple chemotherapeutic drugs and the absence of GADD45 might abrogate their effects in cancer cells. In this review, we present a comprehensive discussion of the functions of GADD45 proteins, linking their regulation to effectors of cell cycle arrest, DNA repair and apoptosis. The ramifications regarding their roles as essential and central players in tumor growth suppression are also examined. We also extensively review recent literature to clarify how different chemotherapeutic drugs induce GADD45 gene expression and how its up-regulation and interaction with different molecular partners may benefit cancer chemotherapy and facilitate novel drug discovery. C1 [Tamura, R. E.; Zerbini, L. F.] Int Ctr Genet Engn & Biotechnol, ZA-7925 Cape Town, South Africa. [Tamura, R. E.; Zerbini, L. F.] Univ Cape Town, Med Biochem Div, ZA-7925 Cape Town, South Africa. [de Vasconcellos, J. F.] Ctr Infantil Boldrini, Mol Biol Lab, Campinas, SP, Brazil. [de Vasconcellos, J. F.] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, Campinas, SP, Brazil. [Sarkar, D.; Fisher, P. B.] Virginia Commonwealth Univ, Dept Human & Mol Genet, VCU Inst Mol Med, VCU Massey Canc Ctr,Sch Med, Richmond, VA USA. [Libermann, T. A.; Zerbini, L. F.] Beth Israel Deaconess Med Ctr, BIDMC Genom & Prote Ctr, Boston, MA 02215 USA. [Libermann, T. A.; Zerbini, L. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Zerbini, LF (reprint author), Int Ctr Genet Engn & Biotechnol, Wernher & Beit Bldg S,UCT Campus,Anzio Rd, ZA-7925 Cape Town, South Africa. EM luiz.zerbini@uct.ac.za RI tamura, rodrigo/O-9846-2014; Zerbini, Luiz /B-7720-2015 OI tamura, rodrigo/0000-0001-7767-0887; FU International Centre for Genetic Engineering and Biotechnology; CAPES [1102-08-7]; FAPESP [06/01158-3]; NIH [1R01 CA85467, P50 CA090381, P50 CA105009, 1R01 CA097318, 1R01 CA127641, P01 CA104177, R01 CA138540]; Hershey Foundation; Samuel Waxman Cancer Research Foundation; National Foundation for Cancer Research; Department of Defense [PC051217, OC0060439] FX R.E.T. was supported by an International Centre for Genetic Engineering and Biotechnology fellowship. J.F.V. was recipient of a CAPES international fellowship (1102-08-7) and FAPESP 06/01158-3. This work was supported by NIH grants 1R01 CA85467, P50 CA090381, P50 CA105009 and the Hershey Foundation (T.A.L.); NIH grants 1R01 CA097318, 1R01 CA127641, P01 CA104177 and grants from the Samuel Waxman Cancer Research Foundation and the National Foundation for Cancer Research (P.B.F.); NIH grant R01 CA138540 (D.S.); and Department of Defense grants PC051217 and OC0060439 (L.F.Z.). D.S. is a Harrison Endowed Scholar in Cancer Research and a Blick Scholar. P.B.F. holds the Thelma Newmeyer Corman Chair in Cancer Research in the VCU Massey Cancer Center and is a SWCRF and a NFCR Investigator. NR 195 TC 60 Z9 64 U1 2 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD JUN PY 2012 VL 12 IS 5 BP 634 EP 651 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942MD UT WOS:000304047300012 PM 22515981 ER PT J AU Sosenko, JM Skyler, JS Herold, KC Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Herold, Kevan C. Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp Diabet Prevention Trial-Type 1 TI The Metabolic Progression to Type 1 Diabetes as Indicated by Serial Oral Glucose Tolerance Testing in the Diabetes Prevention Trial-Type 1 SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; C-PEPTIDE; CLINICAL-MANIFESTATIONS; NATURAL-HISTORY; RISK SCORE; MELLITUS; ONSET; SECRETION; RELATIVES C1 [Sosenko, Jay M.; Skyler, Jay S.] Univ Miami, Miller Sch Med, Div Endocrinol, Miami, FL 33136 USA. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Miller Sch Med, Div Endocrinol, Miami, FL 33136 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016; OI Gallagher, Mary/0000-0002-5844-2309 FU Type 1 Diabetes TrialNet Study Group; National Institutes of Health (NTH) through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK-061010, U01 DK-061016, U01 DK-061034, U01 DK-061036, U01 DK-061040, U01 DK-061041, U01 DK-061042, U01 DK-061055, U01 DK-061058, U01 DK-084565, U01 DK-085453, U01 DK-085461, U01 DK-085463, U01 DK-085466, U01 DK-085499, U01 DK-085505, U01 DK-085509, HHSN267200800019C]; National Center for Research Resources [UL1 RR-024131, UL1 RR-024139, UL1 RR-024153, UL1 RR-024975, UL1 RR-024982, UL1 RR-025744, UL1 RR-025761, UL1 RR-025780, UL1 RR-029890, UL1 RR-031986]; General Clinical Research Center [M01 RR-00400]; Juvenile Diabetes Research Foundation International (JDRF); ADA FX The sponsor of the study was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NTH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK-061010, U01 DK-061016, U01 DK-061034, U01 DK-061036, U01 DK-061040, U01 DK-061041, U01 DK-061042, U01 DK-061055, U01 DK-061058, U01 DK-084565, U01 DK-085453, U01 DK-085461, U01 DK-085463, U01 DK-085466, U01 DK-085499, U01 DK-085505, and U01 DK-085509, and a contract HHSN267200800019C; the National Center for Research Resources, through Clinical Translational Science Awards UL1 RR-024131, UL1 RR-024139, UL1 RR-024153, UL1 RR-024975, UL1 RR-024982, UL1 RR-025744, UL1 RR-025761, UL1 RR-025780, UL1 RR-029890, and UL1 RR-031986, and General Clinical Research Center Award M01 RR-00400; the Juvenile Diabetes Research Foundation International (JDRF); and the ADA. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, JDRF, or ADA. NR 50 TC 18 Z9 19 U1 0 U2 6 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 2012 VL 61 IS 6 BP 1331 EP 1337 DI 10.2337/db11-1660 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 948FX UT WOS:000304490100004 PM 22618768 ER PT J AU Haiman, CA Fesinmeyer, MD Spencer, KL Buzkova, P Voruganti, VS Wan, P Haessler, J Franceschini, N Monroe, KR Howard, BV Jackson, RD Florez, JC Kolonel, LN Buyske, S Goodloe, RJ Liu, SM Manson, JE Meigs, JB Waters, K Mukamal, KJ Pendergrass, SA Shrader, P Wilkens, LR Hindorff, LA Ambite, JL North, KE Peters, U Crawford, DC Le Marchand, L Pankow, JS AF Haiman, Christopher A. Fesinmeyer, Megan D. Spencer, Kylee L. Buzkova, Petra Voruganti, V. Saroja Wan, Peggy Haessler, Jeff Franceschini, Nora Monroe, Kristine R. Howard, Barbara V. Jackson, Rebecca D. Florez, Jose C. Kolonel, Laurence N. Buyske, Steven Goodloe, Robert J. Liu, Simin Manson, JoAnn E. Meigs, James B. Waters, Kevin Mukamal, Kenneth J. Pendergrass, Sarah A. Shrader, Peter Wilkens, Lynne R. Hindorff, Lucia A. Ambite, Jose Luis North, Kari E. Peters, Ulrike Crawford, Dana C. Le Marchand, Loic Pankow, James S. TI Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; LARGE-SCALE ASSOCIATION; TCF7L2 GENE; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; SUSCEPTIBILITY LOCI; AFRICAN-AMERICANS; DESIGN; INDIANS; CDKAL1 AB Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P-heterogeneity < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations. Diabetes 61:1642-1647, 2012 C1 [Haiman, Christopher A.; Wan, Peggy; Monroe, Kristine R.; Waters, Kevin] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Fesinmeyer, Megan D.; Haessler, Jeff; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Spencer, Kylee L.; Goodloe, Robert J.; Pendergrass, Sarah A.; Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA. [Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Voruganti, V. Saroja] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Howard, Barbara V.] Georgetown Univ, Washington, DC USA. [Howard, Barbara V.] Medstar Hlth Res Inst, Washington, DC USA. [Jackson, Rebecca D.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Florez, Jose C.; Manson, JoAnn E.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Kolonel, Laurence N.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Buyske, Steven] Rutgers State Univ, Dept Genet & Stat, Piscataway, NJ USA. [Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Manson, JoAnn E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Meigs, James B.; Shrader, Peter] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NHGRI, NIH, Off Populat Gen, Bethesda, MD 20892 USA. [Ambite, Jose Luis] Univ So Calif, Inst Informat Sci, Los Angeles, CA USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Haiman, CA (reprint author), Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. EM haiman@usc.edu RI Crawford, Dana/C-1054-2012; Liu, Simin/I-3689-2014; OI Liu, Simin/0000-0003-2098-3844; Pankow, James/0000-0001-7076-483X FU National Human Genome Research Institute; [U01HG004803]; [U01HG004798]; [U01HG004802]; [U01HG004790]; [U01HG004801] FX The PAGE program is funded by the National Human Genome Research Institute, supported by U01HG004803 (CALiCo [Causal Variants Across the Life Course]), U01HG004798 (EAGLE [Epidemiologic Architecture of Genes Linked to Environment]), U01HG004802 (MEG [Multiethnic Cohort]), U01HG004790 ('WHI [Women's Health Initiative]), and UO1HG004801 (Coordinating Center). NR 44 TC 30 Z9 30 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2012 VL 61 IS 6 BP 1642 EP 1647 DI 10.2337/db11-1296 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 948FX UT WOS:000304490100043 PM 22474029 ER PT J AU Rapuano, BE Lee, JJE MacDonald, DE AF Rapuano, Bruce E. Lee, Jani J. E. MacDonald, Daniel E. TI Titanium alloy surface oxide modulates the conformation of adsorbed fibronectin to enhance its binding to alpha(5)beta(1) integrins in osteoblasts SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE conformation; fibronectin; integrins; osteoblast; titanium alloy ID HUMAN PLASMA FIBRONECTIN; ATOMIC-FORCE MICROSCOPY; AMINO-ACID-SEQUENCE; CELL-ADHESION; CHEMICAL-MODIFICATION; BONE SIALOPROTEIN; SYNERGY SITE; NET CHARGE; IN-VITRO; ATTACHMENT AB Rapuano BE, Lee JJE, MacDonald DE. Titanium alloy surface oxide modulates the conformation of adsorbed fibronectin to enhance its binding to a5 beta 1 integrins in osteoblasts. ?Eur J Oral Sci 2012; 120: 185194. (C) 2012 Eur J Oral Sci Our laboratory has previously demonstrated that heat (600 degrees C) or radiofrequency plasma glow discharge (RFGD) pretreatment of a titanium alloy (Ti6Al4V) increased the net negative charge of the alloy's surface oxide and the attachment of osteoblastic cells to adsorbed fibronectin. The purpose of the current study was to investigate the biological mechanism by which these surface pretreatments enhance the capacity of fibronectin to stimulate osteoblastic cell attachment. Each pretreatment was found to increase the binding (measured by ELISA) of a monoclonal anti-fibronectin Ig to the central integrin-binding domain of adsorbed fibronectin, and to increase the antibody's inhibition of osteogenic cell attachment (measured by hexosaminidase assay). Pretreatments also increased the binding (measured by ELISA) of anti-integrin IgGs to the a5 and beta 1 integrin subunits that became attached to fibronectin during cell incubation. These findings suggest that negatively charged surface oxides of Ti6Al4V cause conformational changes in fibronectin that increase the availability of its integrin-binding domain to a5 beta 1 integrins. C1 [Rapuano, Bruce E.; Lee, Jani J. E.; MacDonald, Daniel E.] Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10021 USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY USA. RP MacDonald, DE (reprint author), Cornell Univ, Weill Med Coll, Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM dem14@columbia.edu FU NIH [RO1 DE017695]; National Center for Research Resources, NIH [C06- RR12538-01] FX The project described was supported by Grant Number NIH RO1 DE017695 (awarded to D.E.M.). This material is also the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York. This investigation was also conducted at the HSS research facility constructed with support of Grant C06- RR12538-01 from the National Center for Research Resources, NIH. We would like to acknowledge Dr Stephen Doty and Tony Labisserie for their help with scanning electron microscopy. Special thanks go to Tiffany Leung, Ryan Jeong, and Kyle Hackshaw for their technical assistance. NR 51 TC 14 Z9 15 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD JUN PY 2012 VL 120 IS 3 BP 185 EP 194 DI 10.1111/j.1600-0722.2012.954_e.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 944HC UT WOS:000304188900002 PM 22607334 ER PT J AU Yamauchi, M Lochhead, P Morikawa, T Huttenhower, C Chan, AT Giovannucci, E Fuchs, C Ogino, S AF Yamauchi, Mai Lochhead, Paul Morikawa, Teppei Huttenhower, Curtis Chan, Andrew T. Giovannucci, Edward Fuchs, Charles Ogino, Shuji TI Colorectal cancer: a tale of two sides or a continuum? SO GUT LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; POPULATION-BASED SAMPLE; COLON-CANCER; MICROSATELLITE INSTABILITY; BIRTH-COHORT; TRENDS; DISTAL; EXPRESSION; MORTALITY C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Mol Oncol Pathol,Dana Farber Canc Inst,Dept M, Boston, MA 02215 USA. [Yamauchi, Mai; Lochhead, Paul; Morikawa, Teppei; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Mol Oncol Pathol,Dana Farber Canc Inst,Dept M, 450 Brookline Ave,Room JF 215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu OI Huttenhower, Curtis/0000-0002-1110-0096 FU US National Institute of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA118553, R01 CA151993, R01 CA137178]; US National Science Foundation [DBI-1053486]; Harvard University; Japan Society for Promotion of Science FX This work was supported by US National Institute of Health grants (P01 CA87969 to S E Hankinson, P01 CA55075 to W C Willett, P50 CA127003 to CSF, R01 CA118553 to CSF, R01 CA151993 to SO and R01 CA137178 to ATC) and a US National Science Foundation grant (DBI-1053486 to CH). PL is a Scottish Government Clinical Academic Fellow and is supported by a Harvard University Knox Memorial Fellowship. TM was supported by a fellowship grant from the Japan Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of US NIH. Funding agencies did not have any role in the design of the study; the collection, analysis, or interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. NR 53 TC 96 Z9 98 U1 0 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2012 VL 61 IS 6 BP 794 EP 797 DI 10.1136/gutjnl-2012-302014 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 941WG UT WOS:000303997800005 PM 22490520 ER PT J AU Yamauchi, M Morikawa, T Kuchiba, A Imamura, Y Qian, ZR Nishihara, R Liao, XY Waldron, L Hoshida, Y Huttenhower, C Chan, AT Giovannucci, E Fuchs, C Ogino, S AF Yamauchi, Mai Morikawa, Teppei Kuchiba, Aya Imamura, Yu Qian, Zhi Rong Nishihara, Reiko Liao, Xiaoyun Waldron, Levi Hoshida, Yujin Huttenhower, Curtis Chan, Andrew T. Giovannucci, Edward Fuchs, Charles Ogino, Shuji TI Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum SO GUT LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; BODY-MASS INDEX; DNA METHYLATION; COLON-CANCER; MICROSATELLITE INSTABILITY; LINE-1 HYPOMETHYLATION; P-GLYCOPROTEIN; BRAF MUTATION; EXPRESSION AB Objective Colorectal cancer is typically classified into proximal colon, distal colon and rectal cancer. Tumour genetic and epigenetic features differ by tumour location. Considering a possible role of bowel contents (including microbiome) in carcinogenesis, this study hypothesised that tumour molecular features might gradually change along bowel subsites, rather than change abruptly at splenic flexure. Design Utilising 1443 colorectal cancers in two US nationwide prospective cohort studies, the frequencies of molecular features (CpG island methylator phenotype (CIMP), microsatellite instability (MSI), LINE-1 methylation and BRAF, KRAS and PIK3CA mutations) were examined along bowel subsites (rectum, rectosigmoid junction, sigmoid, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon and caecum). The linearity and non-linearity of molecular relations along subsites were statistically tested by multivariate logistic or linear regression analysis. Results The frequencies of CIMP-high, MSI-high and BRAF mutations gradually increased from the rectum (<2.3%) to ascending colon (36-40%), followed by falls in the caecum (12-22%). By linearity tests, these molecular relations were significantly linear from rectum to ascending colon (p<0.0001), and there was little evidence of non-linearity (p>0.09). Caecal cancers exhibited the highest frequency of KRAS mutations (52% vs 27-35% in other sites; p<0.0001). Conclusions The frequencies of CIMP-high, MSI-high and BRAF mutations in cancer increased gradually along colorectum subsites from the rectum to ascending colon. These novel data challenge the common conception of discrete molecular features of proximal versus distal colorectal cancers, and have a substantial impact on clinical, translational and epidemiology research, which has typically been performed with the dichotomous classification of proximal versus distal tumours. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Mol Oncol Pathol,Dana Farber Canc Inst,Dept M, Boston, MA 02215 USA. [Yamauchi, Mai; Morikawa, Teppei; Kuchiba, Aya; Imamura, Yu; Qian, Zhi Rong; Nishihara, Reiko; Liao, Xiaoyun; Waldron, Levi; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Waldron, Levi; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Waldron, Levi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hoshida, Yujin] Broad Inst Massachusetts Inst Technol & Harvard U, Canc Program, Cambridge, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Mol Oncol Pathol,Dana Farber Canc Inst,Dept M, 450 Brookline Ave,Room JF 215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120; Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096 FU US National Institutes of Health [P01CA87969, P01CA55075, P50CA127003, R01CA151993, R01CA137178]; Bennett Family Fund for Targeted Therapies Research; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan Society for the Promotion of Science FX This work was supported by US National Institutes of Health grants (P01CA87969 (to SE Hankinson), P01CA55075 (to WC Willett), P50CA127003 (to CSF), R01CA151993 (to SO) and R01CA137178 (to ATC)); the Bennett Family Fund for Targeted Therapies Research; and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. TM was supported by a fellowship grant from the Japan Society for the Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. Funding agencies did not have any role in the design of the study, the collection, analysis, or interpretation of the data, the decision to submit the manuscript for publication or the writing of the manuscript. NR 57 TC 181 Z9 190 U1 4 U2 26 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2012 VL 61 IS 6 BP 847 EP 854 DI 10.1136/gutjnl-2011-300865 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 941WG UT WOS:000303997800013 PM 22427238 ER PT J AU Williams, DR Kontos, EZ Viswanath, K Haas, JS Lathan, CS MacConaill, LE Chen, JV Ayanian, JZ AF Williams, David R. Kontos, Emily Z. Viswanath, K. Haas, Jennifer S. Lathan, Christopher S. MacConaill, Laura E. Chen, Jarvis Ayanian, John Z. TI Integrating Multiple Social Statuses in Health Disparities Research: The Case of Lung Cancer SO HEALTH SERVICES RESEARCH LA English DT Article DE Health care disparities; smoking; lung cancer; race; ethnicity; socioeconomic status; gender ID SOCIOECONOMIC-STATUS; UNITED-STATES; RACIAL-DIFFERENCES; CIGARETTE-SMOKING; RESIDENTIAL SEGREGATION; ETHNIC DISPARITIES; AFRICAN-AMERICANS; RACE; US; MORTALITY AB Objective To illustrate the complex patterns that emerge when race/ethnicity, socioeconomic status (SES), and gender are considered simultaneously in health care disparities research and to outline the needed research to understand them by using disparities in lung cancer risks, treatment, and outcomes as an example. Principal Findings SES, gender, and race/ethnicity are social categories that are robust predictors of variations in health and health services utilization. These are usually considered separately, but intersectionality theory indicates that the impact of each depends on the others. Each reflects historically and culturally contingent variations in social, economic, and political status. Distinct patterns of risk and resilience emerge at the intersections of multiple social categories and shape the experience of health, health care access, utilization, quality, and outcomes where these categories intersect. Intersectional approaches call for greater attention to understand social processes at multiple levels of society and require the collection of relevant data and utilization of appropriate analytic approaches to understand how multiple risk factors and resources combine to affect the distribution of disease and its management. Conclusions Understanding how race/ethnicity, gender, and SES are interactive, interdependent, and social identities can provide new knowledge to enhance our efforts to effectively address health disparities. C1 [Williams, David R.; Kontos, Emily Z.; Chen, Jarvis] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. [Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Haas, Jennifer S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Lathan, Christopher S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Dept Med, Boston, MA 02215 USA. [MacConaill, Laura E.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Hlth Care Policy,Div Gen Med, Boston, MA 02215 USA. RP Kontos, EZ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 401 Pk Dr,4th Floor W, Boston, MA 02215 USA. EM ekontos@hsph.harvard.edu FU National Cancer Institute's Lung Cancer Disparities Center [1P50CA148596]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX This work was conducted with support from the National Cancer Institute's Lung Cancer Disparities Center grant 1P50CA148596 and in part (for Drs. Ayanian and Haas) with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. The authors would also like to thank the Center's Program Coordinator, Maria Simoneau, for her dedication to the formatting of this manuscript and the administrative oversight of the submission process. The co-authors report no conflict of interest. NR 84 TC 41 Z9 41 U1 2 U2 36 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2012 VL 47 IS 3 BP 1255 EP 1277 DI 10.1111/j.1475-6773.2012.01404.x PN 2 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 939HO UT WOS:000303800300003 PM 22568674 ER PT J AU Lapatin, S Goncalves, M Nillni, A Chavez, L Quinn, RL Green, A Alegria, M AF Lapatin, Sheri Goncalves, Marta Nillni, Anna Chavez, Ligia Quinn, Roxana Llerena Green, Alexander Alegria, Margarita TI Lessons from the Use of Vignettes in the Study of Mental Health Service Disparities SO HEALTH SERVICES RESEARCH LA English DT Article DE Vignettes; disparities; mental health services ID RHEUMATOID-ARTHRITIS; CLINICAL JUDGMENT AB Objective To examine the development, feasibility, and use of a vignette approach as an important tool in health services disparities research. Data Source Interviews with vignette developers and qualitative data from a novel mental health services disparities study that used vignettes in two samples: (1) predominantly low-income parents of children attending mental health specialty care who were Latino or non-Latino White and (2) Latino and non-Latino mental health clinicians who treat children in their practice. Study Design We conduct a content analysis of qualitative data from patients and providers in the Ethnic Differences Study to explore the feasibility of vignette methodology in health services disparities research, and we identify lessons learned that may guide future vignette development. Principal Findings Vignettes provide a valuable approach that is acceptable to participants, elicits important insight on participant experience and services, and sheds light on factors that can help optimize study design for exploring health disparities questions. Conclusions Researchers, clinicians, and others should consider a set of factors that help determine when a vignette approach is warranted in research, training, or for other uses, including how best to address identified weaknesses. C1 [Lapatin, Sheri; Alegria, Margarita] Harvard Univ, Sch Med, Ctr Multicultural Mental Hlth Res, Cambridge Hlth Alliance, Somerville, MA 02143 USA. [Goncalves, Marta] Harvard Univ, Sch Med, Cambridge Hlth Alliance,Mental Hlth Res, Lisbon Univ Inst ISCTE IUL,Ctr Multicultural, Lisbon, Portugal. [Nillni, Anna] NYU, Steinhardt Sch Media Culture & Commun, New York, NY USA. [Chavez, Ligia] Univ Puerto Rico, San Juan, PR 00936 USA. [Quinn, Roxana Llerena] Childrens Hosp Boston, Dept Psychiat, Boston, MA USA. [Green, Alexander] Massachusetts Gen Hosp, Disparities Solut Ctr, Boston, MA 02114 USA. RP Lapatin, S (reprint author), Harvard Univ, Sch Med, Ctr Multicultural Mental Hlth Res, Cambridge Hlth Alliance, 120 Beacon St,4th Floor, Somerville, MA 02143 USA. EM slapatin@charesearch.com OI Goncalves, Marta/0000-0002-0232-2631; Markle, Sheri/0000-0002-6768-3569 FU NIH [1P50MH 073469]; National Institute of Mental Health; National Institute on Minority Health and Health Disparities [P60 MD 002261] FX This study was supported by NIH Research Grant 1P50MH 073469 funded by the National Institute of Mental Health and P60 MD 002261 (NIMHD) funded by the National Institute on Minority Health and Health Disparities. The authors thank Norah Mulvaney-Day, Marcela Horvitz-Lennon, Benjamin Cook, John Ayanian, LeRoi Hicks, and Emily Zobel Kontos for their valuable feedback on previous drafts; Yaminette Diaz, for her contributions to study setup and implementation in Boston site; Sabrina Gonzalez for conducting parent interviews; and Rachel Shapiro for her input on recruitment. NR 27 TC 8 Z9 8 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2012 VL 47 IS 3 BP 1345 EP 1362 DI 10.1111/j.1475-6773.2011.01360.x PN 2 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 939HO UT WOS:000303800300007 PM 22150766 ER PT J AU Shields, AE Crown, WH AF Shields, Alexandra E. Crown, William H. TI Looking to the Future: Incorporating Genomic Information into Disparities Research to Reduce Measurement Error and Selection Bias SO HEALTH SERVICES RESEARCH LA English DT Article DE Health economics; social determinants of health; racial; ethnic differences in health and health care; personalized medicine; genomics ID HER2-POSITIVE BREAST-CANCER; ELECTRONIC HEALTH RECORDS; GENE-ENVIRONMENT INTERACTION; AFRICAN-AMERICANS; ADJUVANT CHEMOTHERAPY; SUSCEPTIBILITY LOCI; WIDE ASSOCIATION; MEDICAL-RECORDS; NATIONAL-SURVEY; LUNG-CANCER AB Objective To extend recent conceptual and methodological advances in disparities research to include the incorporation of genomic information in analyses of racial/ethnic disparities in health care and health outcomes. Data Sources Published literature on human genetic variation, the role of genetics in disease and response to treatment, and methodological developments in disparities research. Study Design We present a conceptual framework for incorporating genomic information into the Institute of Medicine definition of racial/ethnic disparities in health care, identify key concepts used in disparities research that can be informed by genomics research, and illustrate the incorporation of genomic information into current methods using the example of HER-2 mutations guiding care for breast cancer. Principal Findings Genomic information has not yet been incorporated into disparities research, though it has direct relevance to concepts of race/ethnicity, health status, appropriate care, and socioeconomic status. The HER-2 example demonstrates how available genetic information can be incorporated into current disparities methods to reduce selection bias and measurement error. Advances in health information infrastructure may soon make standardized genetic information more available to health services researchers. Conclusion Genomic information can refine measurement of racial/ethnic disparities in health care and health outcomes and should be included wherever possible in disparities research. C1 [Shields, Alexandra E.] Massachusetts Gen Hosp, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02114 USA. [Shields, Alexandra E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Crown, William H.] OptumInsight Life Sci, Waltham, MA USA. RP Shields, AE (reprint author), 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM ashields@partners.org FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; National Human Genome Research Institute [R01 HG003475-03]; OptumInsight Fellowship Program FX The authors thank Tom McGuire, Wylie Burke, Mehdi Najafzadeh, and John Ayanian for comments on earlier drafts of this manuscript. Carly Hudelson, Marcelo Cerullo, and Anna Boonin Schachter also deserve special thanks for their superb research assistance. This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. This work was also supported by a grant from the National Human Genome Research Institute R01 HG003475-03 (A. Shields) and the OptumInsight Fellowship Program (W. Crown). NR 79 TC 7 Z9 7 U1 3 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2012 VL 47 IS 3 BP 1387 EP 1410 DI 10.1111/j.1475-6773.2012.01413.x PN 2 PG 24 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 939HO UT WOS:000303800300009 PM 22515190 ER PT J AU Qi, H Liu, JP Deng, CY Zhou, HX Deng, SP Li, FR AF Qi, Hui Liu, Jin-Peng Deng, Chun-Yan Zhou, Han-Xin Deng, Shao-Ping Li, Fu-Rong TI A role for anti-CD45RB monoclonal antibody treatment upon dendritic cells SO IMMUNOLOGIC RESEARCH LA English DT Article DE Anti-CD45RB monoclonal antibody; Dendritic cells; Exosome; Immune tolerance ID REGULATORY T-CELLS; ISLET ALLOGRAFT SURVIVAL; TRANSPLANT TOLERANCE; EXOSOMES; ACTIVATION; MATURATION; RECEPTOR; CD45; IMMUNOSUPPRESSION; PHOSPHATASE AB Selective interference with CD45RB isoform by monoclonal antibody (anti-CD45RBmAb) reliably induces donor-specific tolerance. Dendritic cells (DCs) are the most potent antigen-presenting cells that are capable of activating na < ve T cells. The purposes of the present study were to investigate the roles of anti-CD45RBmAb on the phenotypes and functioning of DCs and to further illustrate the mechanism of anti-CD45RBmAb-inducing immunologic tolerance. DCs from C57BL/6 mice were cultured and treated with various doses of anti-CD45RB monoclonal antibody. Cell phenotype, cycle and phagocytic ability were detected by flow cytometry. The production of IL-10 and IL-12 in the supernatants of mature DCs was measured with ELISA. Exosomes (Dex) were recovered from the supernatant of DCs cultured for 6 days in depleted medium, and effects of DCs and Dex on the ability of T-cell proliferation were detected by mixed lymphocyte culture. Anti-CD45RBmAb could inhibit DCs maturation in a dose-dependent manner, and the effects of exosomes (Dex) on DCs enhance or inhibition proliferation of T cells were also in a dose-dependent manner. Anti-CD45RBmAb could profoundly inhibit the maturation and functioning of DCs and generate tolerogenic dendritic cells (tDCs) as well as Dex, suggesting mechanistic contributions to tolerance development from the DCs through interactions with T cells. C1 [Qi, Hui; Liu, Jin-Peng; Deng, Chun-Yan; Zhou, Han-Xin; Deng, Shao-Ping; Li, Fu-Rong] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Res Ctr, Clin Med Coll 2, Shenzhen 518020, Peoples R China. [Deng, Shao-Ping] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA USA. [Li, Fu-Rong] Shenzhen Inst Gerontol, Shenzhen 518020, Peoples R China. RP Li, FR (reprint author), Jinan Univ, Shenzhen Peoples Hosp, Clin Med Res Ctr, Clin Med Coll 2, 1017 Dongmen N Rd, Shenzhen 518020, Peoples R China. EM dengs60@yahoo.com.cn; frli62@yahoo.com FU National Natural Science Foundation of China [30772042]; The Natural Science Foundation of Guangdong [6027540]; The Science and Technology Project of Shenzhen [200601017]; Medical Science and Technology Foundation of Guangdong [B2008158] FX This work was supported by the National Natural Science Foundation of China (No. 30772042), The Natural Science Foundation of Guangdong (No. 6027540) and The Science and Technology Project of Shenzhen (No. 200601017) and the Medical Science and Technology Foundation of Guangdong (No. B2008158). NR 31 TC 4 Z9 4 U1 1 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD JUN PY 2012 VL 52 IS 3 BP 250 EP 257 DI 10.1007/s12026-012-8336-0 PG 8 WC Immunology SC Immunology GA 943HD UT WOS:000304110600009 PM 22539131 ER PT J AU Labbe, C Boucher, G Foisy, S Alikashani, A Nkwimi, H David, G Beaudoin, M Goyette, P Charron, G Xavier, RJ Rioux, JD AF Labbe, Catherine Boucher, Gabrielle Foisy, Sylvain Alikashani, Azadeh Nkwimi, Herbert David, Genevieve Beaudoin, Melissa Goyette, Philippe Charron, Guy Xavier, Ramnik J. Rioux, John D. TI Genome-wide expression profiling implicates a MAST3-regulated gene set in colonic mucosal inflammation of ulcerative colitis patients SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE MAST3; inflammatory bowel disease; NF-kappa B ID NECROSIS-FACTOR-ALPHA; ZINC-FINGER PROTEIN; KAPPA-B ACTIVATION; CROHNS-DISEASE; BOWEL-DISEASE; TH17 CELLS; INFLIXIMAB; BIOINFORMATICS; SUSCEPTIBILITY; PATHOGENESIS AB Background: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) presumably caused by dysregulated immune responses to the gut microbiota. Genetic association studies have implicated dozens of chromosomal regions or loci in IBD susceptibility. The next challenge is to explain the individual role of each of these modest effect loci in the disease state. We have previously identified MAST3 as an IBD susceptibility gene through genetic fine-mapping of the 19p linkage region. Testing MAST3 in a reporter assay provided preliminary evidence that MAST3 modulates the activity of inflammation-related transcription factor nuclear factor kappa B. Methods: Here we characterized the function of MAST3 through an examination of the influence of the modulation of MAST3 expression on endogenous genome-wide expression patterns. More specifically, we looked at differential gene expression resulting from overexpression and knockdown of the MAST3 gene in epithelial and macrophage cell lines. From we highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-jB activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD. Results: We highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-?B activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD. These MAST3-regulated genes are central to mucosal immune responses. Among them are proinflammatory cytokines (e.g., CCL20, IL8), regulators of NF-?B (e.g., TNFAIP3, LY96, NFKBIA), genes involved in interferon-induced defense against pathogen invasion (e.g., IFIT1, ISG15), and genes involved in cell adhesion and/or migration (e.g., CD44, TMOD1). Conclusions: Taken together, these results confirm MAST3 as a modulator of the inflammatory response through regulation of immune gene expression in the gut of IBD patients. (Inflamm Bowel Dis 2012) C1 [Labbe, Catherine; Boucher, Gabrielle; Foisy, Sylvain; Alikashani, Azadeh; Nkwimi, Herbert; David, Genevieve; Beaudoin, Melissa; Goyette, Philippe; Charron, Guy; Rioux, John D.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Labbe, Catherine; David, Genevieve; Rioux, John D.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Labbe, Catherine; David, Genevieve; Rioux, John D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Labbe, Catherine; David, Genevieve; Rioux, John D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Rioux, JD (reprint author), Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM John.David.Rioux@umontreal.ca RI Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU U.S. National Institute of Diabetes and Digestive and Kidney Diseases [DK062432]; Crohn's and Colitis Foundation of America [SRA512]; Fonds de Recherche en Sante du Quebec FX Funded by grants from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (DK062432) and the Crohn's and Colitis Foundation of America (SRA512) (to J.D.R.). C.L. holds a doctoral training award from the Fonds de Recherche en Sante du Quebec. NR 35 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUN PY 2012 VL 18 IS 6 BP 1072 EP 1080 DI 10.1002/ibd.21887 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 943PR UT WOS:000304137300011 PM 21994190 ER PT J AU Weaver, MJ Harris, MB Strom, AC Smith, RM Lhowe, D Zurakowski, D Vrahas, MS AF Weaver, Michael J. Harris, Mitchel B. Strom, Adam C. Smith, R. Malcolm Lhowe, David Zurakowski, David Vrahas, Mark S. TI Fracture pattern and fixation type related to loss of reduction in bicondylar tibial plateau fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Tibial plateau fractures; Fractures; Fracture fixation AB Introduction: Bicondylar tibial plateau fractures can be treated with locked plating applied from the lateral side with or without additional application of a medial plate (dual plating). Recent studies demonstrate that these injuries can be sub-grouped based upon their morphology by computed tomography (CT). The purpose of this study is to evaluate the relationship between fracture pattern, method of fixation and loss of reduction in bicondylar tibial plateau fractures. Patients and methods: Preoperative CT scans and postoperative plain films were evaluated on a consecutive series of bicondylar tibial plateau fractures. Fracture patterns were classified by CT. Angular alignment was measured immediately postoperatively and again at clinical and radiographic union to assess loss of reduction. Results: A total of 140 patients were studied. Sixty-six (47%) had a single large medial fragment with the articular surface intact, 19 (14%) had a medial articular fracture line with a mainly sagittal component and 55 (39%) had a coronal fracture through the medial articular surface. A total of 129 patients had been treated with lateral locked plating alone whilst 11 patients (all with a coronal fracture of the medial condyle) underwent dual plating. There was little loss of reduction (median subsidence 0.5 degrees) when lateral locked plating was employed alone in patients with a single medial fracture fragment or with a sagittal medial fracture line. When lateral locked plating was used in the presence of a medial coronal fracture line, there was a significantly higher rate of subsidence (median 2.0 degrees) compared to those with no medial fracture line (p = 0.002). Patients with coronal fracture lines treated with dual plating had significantly less loss of reduction that those treated with lateral locked plating (p = 0.01). Conclusions: Most patients with bicondylar tibial plateau fractures do well when treated with lateral locked plating. However, those with a medial coronal fracture line tend to have a higher rate of subsidence and loss of reduction when lateral locked plating is employed alone. These fractures may be better treated with dual plating if the soft tissues allow. (c) 2011 Elsevier Ltd. All rights reserved. C1 [Weaver, Michael J.; Harris, Mitchel B.] Harvard Univ, Brigham & Womens Hosp, Dept Orthopaed Surg, Sch Med, Boston, MA 02115 USA. [Strom, Adam C.] Dartmouth Coll, Hanover, NH 03755 USA. [Smith, R. Malcolm; Lhowe, David; Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Sch Med, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Childrens Hosp Boston, Dept Surg, Sch Med, Boston, MA 02115 USA. RP Weaver, MJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Orthopaed Surg, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM mjweaver@partners.org NR 14 TC 18 Z9 29 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUN PY 2012 VL 43 IS 6 BP 864 EP 869 DI 10.1016/j.injury.2011.10.035 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 942LI UT WOS:000304045100033 PM 22169068 ER PT J AU Zhu, JY Li, LP Li, YX Shi, MY Lu, HY Garnick, DW Weingart, SN AF Zhu, Junya Li, Liping Li, Yuxia Shi, Meiyu Lu, Haiying Garnick, Deborah W. Weingart, Saul N. TI What constitutes patient safety culture in Chinese hospitals? SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE patient safety; quality culture; focus groups; China; hospital ID PSYCHOMETRIC PROPERTIES; HEALTH-CARE; ADVERSE EVENTS; CLIMATE; PERCEPTIONS; INSTRUMENTS; TAIWAN; JAPAN AB To develop a patient safety culture instrument for use in Chinese hospitals, we assessed the appropriateness of existing safety culture questionnaires used in the USA and Japan for Chinese respondents and identified new items and domains suitable to Chinese hospitals. Focus group study. Twenty-four physicians, nurses and other health-care workers from 11 hospitals in three Chinese cities. Three focus groups were conducted in 2010 to elicit information from hospital workers about their perceptions of the appropriateness and importance of each of 97 questionnaire items, derived from a literature review and an expert panel, characterizing hospital safety culture. Participants understood the concepts of patient safety and safety culture and identified features associated with safe care. They judged that numerous questions from existing surveys were inappropriate, including 39 items that were dropped because they were judged unimportant, semantically redundant, confusing, ambiguous or inapplicable in Chinese settings. Participants endorsed eight new items and three additional dimensions addressing staff training, mentoring of new hires, compliance with rules and procedures, equipment availability and leadership walk-rounds they judged appropriate to assessing safety culture in Chinese hospitals. This process resulted in a 66-item instrument for testing in cognitive interviews, the next stage of survey development. Focus group participants provided important insights into the refinement of existing items and the construction of new items for measuring patient safety culture in Chinese hospitals. This is a necessary first step in producing a culturally appropriate instrument applicable to specific local contexts. C1 [Zhu, Junya; Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. [Zhu, Junya; Garnick, Deborah W.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Zhu, Junya; Li, Liping; Li, Yuxia; Shi, Meiyu; Lu, Haiying] Shanghai Univ Tradit Chinese Med, Sch Nursing, Shanghai, Peoples R China. [Weingart, Saul N.] Harvard Univ, Sch Med, Boston, MA 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 RI Garnick, Deborah/I-9009-2012; Davis, Mark/J-5101-2015 FU World Health Organization (WHO) [PS08212] FX We gratefully acknowledge the World Health Organization (WHO) Patient Safety Research Small Grants (grant no. PS08212) for the funding support and guidance. All views expressed in this manuscript are those of the authors and do not necessarily reflect the view of the WHO. NR 43 TC 7 Z9 7 U1 4 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD JUN PY 2012 VL 24 IS 3 BP 250 EP 257 DI 10.1093/intqhc/mzs010 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 944KA UT WOS:000304198700008 PM 22461205 ER PT J AU Moffat, KA Timleck, M Spitzer, E Plumhoff, E Van Cott, E Hayward, CPM AF Moffat, Karen A. Timleck, Marilyn Spitzer, Ernie Plumhoff, Elizabeth Van Cott, Elizabeth Hayward, Catherine P. M. TI ORAL ABSTRACT: EXTERNAL PROFICIENCY TESTING ASSESSMENT - RESULTS OF SURVEYS ON DENSE GRANULE DEFICIENCY SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Moffat, Karen A.; Spitzer, Ernie; Hayward, Catherine P. M.] Hamilton Reg Lab Med Program, Hamilton, ON, Canada. [Moffat, Karen A.; Hayward, Catherine P. M.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Moffat, Karen A.; Plumhoff, Elizabeth; Van Cott, Elizabeth; Hayward, Catherine P. M.] N Amer Specialized Coagulat Lab Assoc, Rochester, MN USA. [Timleck, Marilyn; Hayward, Catherine P. M.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Plumhoff, Elizabeth] Mayo Clin, Rochester, MN USA. [Van Cott, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD JUN PY 2012 VL 34 SU 1 SI SI BP 41 EP 42 PG 2 WC Hematology SC Hematology GA 942YH UT WOS:000304087100048 ER PT J AU Timur, AA Murugesan, G Zhang, L Aung, PP Barnard, J Wang, QK Gaussem, P Silverstein, RL Bhatt, DL Kottke-Marchant, K AF Timur, Ayse Anil Murugesan, Gurunathan Zhang, Li Phyu Phyu Aung Barnard, John Wang, Qing K. Gaussem, Pasacale Silverstein, Roy L. Bhatt, Deepak L. Kottke-Marchant, Kandice TI P2RY1 AND P2RY12 POLYMORPHISMS AND RESIDUAL PLATELET REACTIVITY IN CORONARY ARTERY DISEASE PATIENTS ON ASPIRIN SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Timur, Ayse Anil; Murugesan, Gurunathan; Phyu Phyu Aung; Kottke-Marchant, Kandice] Pathol & Lab Med Inst Cleveland, Cleveland, OH USA. [Wang, Qing K.] Cleveland Clin Cleveland, Ctr Cardiovasc Genet, Cleveland, OH USA. [Wang, Qing K.] Cleveland Clin Cleveland, Dept Mol Cardiol, Cleveland, OH USA. [Gaussem, Pasacale] Univ Paris 05, Inserm U765, AP HP Hop Europeen Georges Pompidou Paris, Paris, France. [Silverstein, Roy L.] Med Coll Wisconsin Milwaukee, Dept Med, Milwaukee, WI USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Med Sch Boston, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD JUN PY 2012 VL 34 SU 1 SI SI BP 90 EP 90 PG 1 WC Hematology SC Hematology GA 942YH UT WOS:000304087100141 ER PT J AU Thompson, GR Wiederhold, NP Najvar, LK Bocanegra, R Kirkpatrick, WR Graybill, JR Patterson, TF AF Thompson, George R., III Wiederhold, Nathan P. Najvar, Laura K. Bocanegra, Rosie Kirkpatrick, William R. Graybill, John R. Patterson, Thomas F. TI A murine model of Cryptococcus gattii meningoencephalitis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE cryptococcal meningoencephalitis; C; gattii; Cryptococcus neoformans; posaconazole; fluconazole ID NEOFORMANS; MENINGITIS; OUTBREAK; FLUCONAZOLE; FLUCYTOSINE; GENOTYPE; VARIETY AB Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by C. gattii. Mice were inoculated intracranially with either C. gattii (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii infecting inocula were compared with a fixed inoculum of C. neoformans, and differences were assessed by survival, brain tissue fungal burden, serum antigen titres and histopathological changes within brain tissue. For treatment, fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post-inoculation. C. gattii was more virulent than C. neoformans, as evident by shorter median survival, earlier histopathological changes and higher serum antigen titres. However, no differences in fungal burden or dissemination to other organs were observed among the various groups. In treatment studies, both fluconazole and posaconazole improved the median survival of mice infected with either species. However, neither regimen improved the percentage of animals surviving to the predetermined study endpoint. These results demonstrate the virulence of C. gattii meningoencephalitis and the potential of this model for the assessment of new treatment strategies. C1 [Thompson, George R., III] Univ Calif Davis, Div Infect Dis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Thompson, George R., III] Univ Calif Davis, Div Infect Dis, Dept Internal Med, Davis, CA 95616 USA. [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Graybill, John R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Internal Med, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Patterson, Thomas F.] S Texas Vet Hlth Care Syst, Div Infect Dis, Dept Internal Med, San Antonio, TX USA. RP Thompson, GR (reprint author), Univ Calif Davis, Div Infect Dis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. EM grthompson@ucdavis.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [N01-AI-25475]; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX This work was supported by a contract from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (N01-AI-25475) to J. R. G. and T. F. P.; G. R. T. has received research support from Pfizer. N. P. W. has received research support from Pfizer, Schering-Plough, Merck, Basilea and Astellas. J. R. G. has received research support from Pfizer, Merck and Astellas, and has been paid to act as a consultant for Merck. T. F. P. has received research grants from Astellas, Basilea, Merck and Pfizer (to the University of Texas Health Science Center at San Antonio), and has been paid to act as a consultant for Astellas, Basilea, Merck, Pfizer and Toyoma. All other authors: none to declare. NR 19 TC 13 Z9 13 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2012 VL 67 IS 6 BP 1432 EP 1438 DI 10.1093/jac/dks060 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 942RJ UT WOS:000304064400020 PM 22378683 ER PT J AU Huttner, B Jones, M Rubin, MA Madaras-Kelly, K Nielson, C Goetz, MB Neuhauser, MM Samore, MH AF Huttner, Benedikt Jones, Makoto Rubin, Michael A. Madaras-Kelly, Karl Nielson, Christopher Goetz, Matthew Bidwell Neuhauser, Melinda M. Samore, Matthew H. TI Double trouble: how big a problem is redundant anaerobic antibiotic coverage in Veterans Affairs medical centres? SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE antibiotic stewardship; anaerobes; metronidazole; inappropriate antibiotic use ID METRONIDAZOLE; THERAPY AB Objectives: To assess the prevalence of, and the variation in, avoidable use of metronidazole in the Veterans Affairs (VA) healthcare system Methods: Barcode Medication Administration (BCMA) data were retrospectively assessed for all patients hospitalized between January 2006 and December 2010 in acute-care wards of all VA medical centres (VAMCs) with complete BCMA data and at least 10 acute-care non-intensive care unit (ICU) beds. Potentially avoidable metronidazole days of therapy (DOT) were defined as the administration of metronidazole with anotheranti-anaerobic antibiotic on the same day for at least two consecutive days during the same hospitalization. Metronidazole was not considered redundant in combination with another anti-anaerobic agent within 28 days after a positive test for Clostridium difficile and during hospitalizations associated with discharge diagnosis codes for cholecystitis or cholangitis. Results: A total of 128 VAMCs satisfied the inclusion criteria. Over the study period there were a total of 782821 DOT of metronidazole (57.4 DOT per 1000 patient-days), of which 183267 (23.4%) fulfilled the criteria for avoidable metronidazole DOT. The percentage of avoidable metronidazole DOT remained stable over the study period (22.8% in 2006 and 22.9% in 2010) despite a decrease in overall metronidazole use. There was wide variation in the percentage of avoidable metronidazole DOT among facilities (2010: median 20.3%, IQR 15.3%-29.4%). Piperacillin/tazobactam was the most commonly administered drug on avoidable metronidazole DOT (56.8%). Conclusions: Potentially avoidable use of metronidazole affected about a quarter of all days when metronidazole was given. The combination of metronidazole with piperacillin/tazobactam was particularly common and represents a possible target for antibiotic stewardship interventions. C1 [Huttner, Benedikt; Jones, Makoto; Rubin, Michael A.; Samore, Matthew H.] VA Salt Lake City Hlth Care Syst, IDEAS Ctr, Salt Lake City, UT 84148 USA. [Huttner, Benedikt; Jones, Makoto; Rubin, Michael A.; Samore, Matthew H.] Univ Utah, Div Epidemiol, Salt Lake City, UT 84132 USA. [Madaras-Kelly, Karl] Boise VA Med Ctr, Boise, ID 83702 USA. [Madaras-Kelly, Karl] Idaho State Univ, Coll Pharm, Meridian, ID 83713 USA. [Nielson, Christopher] VA Sierra Nevada Hlth Care Syst, Reno, NV 89502 USA. [Goetz, Matthew Bidwell] VA Greater LA Healthcare Syst, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Neuhauser, Melinda M.] Dept Vet Affairs Pharm Benefit Management Serv, Hines, IL USA. RP Huttner, B (reprint author), VA Salt Lake City Hlth Care Syst, IDEAS Ctr, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM huttner.benedikt@gmail.com RI Huttner, Benedikt/M-5616-2014; OI Huttner, Benedikt/0000-0002-1749-9464; Goetz, Matthew/0000-0003-4542-992X FU George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA [CDA 10-030-02]; Geneva University Hospitals, Switzerland FX This material is the result of work supported with resources and the use of facilities at the George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA, a career development award (to M. J., CDA 10-030-02) and a fellowship grant from Geneva University Hospitals, Switzerland (to B. H.). NR 10 TC 10 Z9 11 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2012 VL 67 IS 6 BP 1537 EP 1539 DI 10.1093/jac/dks074 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 942RJ UT WOS:000304064400037 PM 22398652 ER PT J AU Chirinos, JA AF Chirinos, Julio A. TI Arterial Stiffness: Basic Concepts and Measurement Techniques SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Arterial stiffness; Compliance; Distensibility; Pulse wave velocity; Elastic modulus ID PRESSURE WAVE-FORMS; ALL-CAUSE MORTALITY; CAROTID-ARTERY; CARDIOVASCULAR-DISEASE; AORTIC STIFFNESS; IN-VIVO; NONINVASIVE EVALUATION; HYPERTENSIVE PATIENTS; CLINICAL-APPLICATIONS; HEALTHY-INDIVIDUALS AB Arterial stiffness is highly relevant to cardiovascular disease. Arterial stiffness is central to the pathogenesis of isolated systolic hypertension and directly impacts left ventricular afterload, pressure pulsatility in the arterial tree, and its penetration into the microvasculature of target organs such as the brain and kidney. Arterial stiffness is affected by various risk factors and biologic processes. Measurements of arterial stiffness may therefore not only provide information about prevalent processes, but also valuable information regarding the cumulative history of risk factor exposure. Available studies consistently demonstrate that large artery stiffness, measured via carotid-femoral pulse wave velocity, independently predicts the risk of incident cardiovascular events in clinical and community-based cohorts. Understanding the basic principles and definitions related to arterial stiffness is therefore desirable for cardiovascular clinicians and researchers. This introductory paper reviews basic physical principles and definitions regarding arterial stiffness and the most important non-invasive methods for its quantification in vivo. C1 Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Chirinos, JA (reprint author), Univ Penn, Perelman Sch Med, Philadelphia VA Med Ctr, Rm 8B111,Univ & Woodland Av, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu NR 56 TC 38 Z9 38 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD JUN PY 2012 VL 5 IS 3 SI SI BP 243 EP 255 DI 10.1007/s12265-012-9359-6 PG 13 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 943HK UT WOS:000304111300001 PM 22447229 ER PT J AU Agarwalla, P Barnard, Z Fecci, P Dranoff, G Curry, WT AF Agarwalla, Pankaj Barnard, Zachary Fecci, Peter Dranoff, Glenn Curry, William T., Jr. TI Sequential Immunotherapy by Vaccination With GM-CSF-expressing Glioma Cells and CTLA-4 Blockade Effectively Treats Established Murine Intracranial Tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE glioma; vaccine; CTLA-4; GVAX; immunotherapy; GM-CSF ID CENTRAL-NERVOUS-SYSTEM; BRAIN-TUMORS; COMBINATION IMMUNOTHERAPY; CLINICAL ACTIVITY; GLIOBLASTOMA; VACCINES; GROWTH; MECHANISMS; ANTIBODIES; RESPONSES AB Malignant glioma is an incurable disease with a relatively short median survival. Several clinical trials have demonstrated that immunotherapy with vaccination is a safe and possibly effective way of prolonging survival. Antibody-based blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) ligation on T lymphocytes is associated with enhanced antitumor immunity in animal models of cancer and in patients with advanced melanoma. We hypothesized that sequential therapy with granulocyte-macrophage-colony-stimulating factor (GM-CSF)-expressing whole-glioma-cell vaccination and CTLA-4 blockade is an effective strategy for treating established intracranial gliomas. GL261 glioma cells were injected into the right frontal lobes of syngeneic C57/BL6 mice. At days 3, 6, and 9 after tumor implantation, mice were treated with subcutaneous injection of irradiated GM-CSF-expressing GL261 cells. Mice were also treated with intraperitoneal injection of anti-CTLA-4 monoclonal antibodies (mAbs), either at days 3, 6, and 9 or days 12, 15, and 18. Animals were followed for survival. Splenocytes were harvested at day 22 for use in enzyme-linked immunosorbent spot assays. Early treatment of established intracranial gliomas with high-dose CTLA-4 blockade was associated with increased survival in GL261-bearing mice. Later treatment with anti-CTLA-4 monoclonal antibodies did not significantly improve survival compared with control-treated mice. Early vaccination followed by subsequent CTLA-4 blockade was associated with significantly improved survival versus either treatment alone and intensified tumor-specific immunity as measured by interferon-g enzyme-linked immunosorbent spot assay. Sequential immunotherapy with GM-CSF-expressing irradiated glioma cells and CTLA-4 blockade synergistically prolongs survival in mice bearing established intracranial gliomas. C1 [Curry, William T., Jr.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurosurg, Boston, MA 02114 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA. RP Curry, WT (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurosurg, 55 Fruit St,Y9E,, Boston, MA 02114 USA. EM wcurry@partners.org FU Robert Wood Johnson Foundation; Executive Committee on Research, Massachusetts General Hospital; NIH [CA143083] FX W.T.C. was supported by Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation; Physician Scientist Development Award, Executive Committee on Research, Massachusetts General Hospital and G. D. was supported by NIH CA143083. NR 25 TC 45 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUN PY 2012 VL 35 IS 5 BP 385 EP 389 DI 10.1097/CJI.0b013e3182562d59 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 942LM UT WOS:000304045500003 PM 22576343 ER PT J AU Mackay, G House, MD Bloch, E Wolfberg, AJ AF Mackay, Gillian House, Michael D. Bloch, Evan Wolfberg, Adam J. TI A GBS culture collected shortly after GBS prophylaxis may be inaccurate SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE antibiotic prophylaxis; group B streptococcus (GBS); penicillin ID B STREPTOCOCCAL DISEASE; INTRAPARTUM CHEMOPROPHYLAXIS; COLONIZATION; DELIVERY; PREVENTION; TRANSMISSION; PENICILLIN; WOMEN AB Objective: To determine whether a vaginal-rectal culture obtained after antibiotic therapy has begun accurately detects pre-existing colonization with group B streptococcus (GBS). Methods: A prospective cohort study of women presenting at in labor who were known to be colonized with GBS were recruited. A GBS culture was obtained prior to administration of intravenous penicillin prophylaxis and repeated 2 hours following the first dose of penicillin. The two results were compared. Results: Eighty subjects were recruited. Complete results were obtained for 61 (76 %) subjects. Of these, 47 (77 %) had a GBS positive on initial culture. Persistence of GBS 2 hours after antibiotic exposure was seen in 30/47 (64 %). Conversion from GBS positive to GBS negative status was seen in 17/47 (36%). Conclusions: A vaginal-rectal culture for GBS performed after antibiotic prophylaxis has commenced may not accurately reflect a patient's GBS colonization status. C1 [Mackay, Gillian] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Tufts Med Ctr, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Mackay, G (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Tufts Med Ctr, Div Maternal Fetal Med, Founders 4,55 Fruit St, Boston, MA 02114 USA. EM gillmackay@yahoo.co.uk FU George Mitchell Society at Tufts Medical Center FX The authors report no declarations of interest. This study was funded by financial support from The George Mitchell Society at Tufts Medical Center. NR 17 TC 1 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JUN PY 2012 VL 25 IS 6 BP 736 EP 738 DI 10.3109/14767058.2011.596961 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 943CH UT WOS:000304097600036 PM 21801141 ER PT J AU Bianchi, MT Eiseman, NA Cash, SS Mietus, J Peng, CK Thomas, RJ AF Bianchi, Matt T. Eiseman, Nathaniel A. Cash, Sydney S. Mietus, Joseph Peng, Chung-Kang Thomas, Robert J. TI Probabilistic sleep architecture models in patients with and without sleep apnea SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE adult; biological rhythms; computational model; human; sleep disorders ID HEART HEALTH; FRAGMENTATION; WAKEFULNESS; DYNAMICS; PATTERNS; AROUSALS; SWITCH AB Sleep fragmentation of any cause is disruptive to the rejuvenating value of sleep. However, methods to quantify sleep architecture remain limited. We have previously shown that human sleepwake stage distributions exhibit multi-exponential dynamics, which are fragmented by obstructive sleep apnea (OSA), suggesting that Markov models may be a useful method to quantify architecture in health and disease. Sleep stage data were obtained from two subsets of the Sleep Heart Health Study database: control subjects with no medications, no OSA, no medical co-morbidities and no sleepiness (n = 374); and subjects with severe OSA (n = 338). Sleep architecture was simplified into three stages: wake after sleep onset (WASO); non-rapid eye movement (NREM) sleep; and rapid eye movement (REM) sleep. The connectivity and transition rates among eight generator states of a first-order continuous-time Markov model were inferred from the observed (phenotypic) distributions: three exponentials each of NREM sleep and WASO; and two exponentials of REM sleep. Ultradian REM cycling was accomplished by imposing time-variation to REM state entry rates. Fragmentation in subjects with severe OSA involved faster transition probabilities as well as additional state transition paths within the model. The Markov models exhibit two important features of human sleep architecture: multi-exponential stage dynamics (accounting for observed bout distributions); and probabilistic transitions (an inherent source of variability). In addition, the model quantifies the fragmentation associated with severe OSA. Markov sleep models may prove important for quantifying sleep disruption to provide objective metrics to correlate with endpoints ranging from sleepiness to cardiovascular morbidity. C1 [Bianchi, Matt T.; Eiseman, Nathaniel A.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Mietus, Joseph; Peng, Chung-Kang] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Thomas, Robert J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang 7,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org RI Peng, Chung-Kang/E-1489-2011 OI Peng, Chung-Kang/0000-0003-3666-9833 FU Department of Neurology, Massachusetts General Hospital; Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center; Pfizer, Inc.; Merck Co FX The authors thank Scott McKinney, and Drs Andrew Phillips, Elizabeth Klerman and Catherine Chu-Shore for valuable discussions and comments on the manuscript. Dr Bianchi receives funding from the Department of Neurology, Massachusetts General Hospital, and the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center, in collaboration with Pfizer, Inc. and Merck & Co. This funding source had no role in the design, interpretation or publication of this study. This paper represents the work of the authors, and not the Sleep Heart Health Study. NR 33 TC 11 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD JUN PY 2012 VL 21 IS 3 BP 330 EP 341 DI 10.1111/j.1365-2869.2011.00937.x PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 944IE UT WOS:000304191900013 PM 21955148 ER PT J AU Fiorentino, L Saxbe, D Alessi, CA Woods, DL Martin, JL AF Fiorentino, Lavinia Saxbe, Darby Alessi, Cathy A. Woods, Diana Lynn Martin, Jennifer L. TI Diurnal Cortisol and Functional Outcomes in Post-Acute Rehabilitation Patients SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Cortisol; Older adults; Rehabilitation; Inpatient; Functional Status ID PITUITARY-ADRENAL AXIS; NURSING-HOME RESIDENTS; UNDER-THE-CURVE; OLDER-PEOPLE; YOUNG-ADULTS; DEMENTIA; DECLINE; DISEASE; CARDIA; CLOCK AB Background. Cortisol is a stress-related hormone with a robust circadian rhythm where levels typically peak in the morning hours and decline across the day. Although acute cortisol increases resulting from stressors are adaptive, chronic elevated cortisol levels are associated with poor functioning. Studies have shown age-related changes in cortisol levels. The present study investigated the relationship between salivary diurnal cortisol and functional outcomes among older adults undergoing inpatient post-acute rehabilitation. Methods. Thirty-two older adults (mean age 78 years; 84% men) in a Veterans Administration inpatient post-acute rehabilitation unit were studied. Functional outcomes were assessed with the motor component of the Functional Independence Measure (mFIM; where mFIM change = discharge - admission score). Saliva samples were collected on 1 day at wake time, 45 minutes later, 11:30 am, 2 pm, 4:30 pm, and bedtime. We analyzed the relationship between cortisol measures and functional outcomes, demographics, and health measures. Results. The analyses consistently showed that greater functional improvement (mFIM change) from admission to discharge was associated with lower comorbidity scores and higher cortisol levels at 2 pm, 4: 30 pm, and bedtime. A morning cortisol rise was also associated with greater mFIM change. Conclusions. Measurement of cortisol in saliva may be a useful biological marker for identification of patients who are "at risk" of lower benefits from inpatient rehabilitation services and who may require additional assistance or intervention during their post-acute care stay. C1 [Alessi, Cathy A.; Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA. [Fiorentino, Lavinia] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Saxbe, Darby] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Woods, Diana Lynn] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. RP Martin, JL (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St,Bldg 25,Room B136, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU National Institute of Mental Health [T32 MH019934, MH080002, T32 MH019925-11]; National Institute on Aging at the National Institutes of Health [K23 AG028452]; Veterans Administration Health Services Research & Development Service [IIR 01-053-1, IIR 04-321-2, AIA 03-047]; Veterans Affairs Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center FX This work was supported by the National Institute of Mental Health [T32 MH019934 (Jeste), MH080002 (Jeste), and T32 MH019925-11 (Irwin)] and the National Institute on Aging [K23 AG028452 (J.L.M.)] at the National Institutes of Health; Veterans Administration Health Services Research & Development Service (IIR 01-053-1, C. A. A.; IIR 04-321-2, C. A. V.; and AIA 03-047 J.L.M.); and the Veterans Affairs Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center. NR 22 TC 2 Z9 2 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2012 VL 67 IS 6 BP 677 EP 682 DI 10.1093/gerona/glr230 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942OM UT WOS:000304054700013 PM 22219521 ER PT J AU Hyman, BT Yuan, JY AF Hyman, Bradley T. Yuan, Junying TI Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID PROGRAMMED CELL-DEATH; LONG-TERM DEPRESSION; UBIQUITIN-PROTEASOME SYSTEM; ALZHEIMERS-DISEASE; MOUSE MODEL; IN-VIVO; MITOCHONDRIAL DYSFUNCTION; TAU PHOSPHORYLATION; PROTEIN-DEGRADATION; DECREASED APOPTOSIS AB Caspases are cysteine proteases that mediate apoptosis, which is a form of regulated cell death that effectively and efficiently removes extra and unnecessary cells during development. In the mature nervous system, caspases are not only involved in mediating cell death but also regulatory events that are important for neural functions, such as axon pruning and synapse elimination, which are necessary to refine mature neuronal circuits. Furthermore, caspases can be reactivated to cause cell death as well as non-lethal changes in neurons during numerous pathological processes. Thus, although a global activation of caspases leads to apoptosis, restricted and localized activation may control normal physiology and pathophysiology in living neurons. This Review explores the multiple roles of caspase activity in neurons. C1 [Hyman, Bradley T.] Massachusetts Gen Hosp, Neurol Serv, Charlestown, MA 01029 USA. [Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Neurol Serv, 114 16th St, Charlestown, MA 01029 USA. EM bhyman@partners.org; jyuan@hms.harvard.edu NR 99 TC 107 Z9 113 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUN PY 2012 VL 13 IS 6 BP 395 EP 406 DI 10.1038/nrn3228 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 944JP UT WOS:000304197000009 PM 22595785 ER PT J AU D'Souza, DC Fridberg, DJ Skosnik, PD Williams, A Roach, B Singh, N Carbuto, M Elander, J Schnakenberg, A Pittman, B Sewell, RA Ranganathan, M Mathalon, D AF D'Souza, Deepak Cyril Fridberg, Daniel J. Skosnik, Patrick D. Williams, Ashley Roach, Brian Singh, Nagendra Carbuto, Michelle Elander, Jacqueline Schnakenberg, Ashley Pittman, Brian Sewell, R. Andrew Ranganathan, Mohini Mathalon, Daniel TI Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Delta(9)-THC in Humans SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Delta(9)-THC; cannabinoids; cannabis; P300; perception; psychosis ID CANNABINOID CB1 RECEPTOR; SELECTIVE ATTENTION; METABOTROPIC GLUTAMATE; MEDIATED INHIBITION; MARIJUANA SMOKING; EVOKED-POTENTIALS; NOVELTY DETECTION; AUDITORY-STIMULI; FREQUENT USERS; HUMAN BRAIN AB Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Delta(9)-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n = 26) completed three test days during which they received intravenous Delta(9)-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory 'oddball' P300 task). Delta(9)-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Delta(9)-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Delta(9)-THC induced psychotomimetic effects, perceptual alterations, and subjective 'high' in a dose-dependent manner. Delta(9)-THC -induced reductions in P3b amplitude correlated with Delta(9)-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Delta(9)-THC, there were no dose-related effects of Delta(9)-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Delta(9)-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing. Neuropsychopharmacology (2012) 37, 1632-1646; doi:10.1038/npp.2012.8; published online 15 February 2012 C1 [D'Souza, Deepak Cyril; Skosnik, Patrick D.; Williams, Ashley; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R. Andrew; Ranganathan, Mohini] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. [D'Souza, Deepak Cyril; Skosnik, Patrick D.; Williams, Ashley; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R. Andrew; Ranganathan, Mohini; Mathalon, Daniel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Roach, Brian; Mathalon, Daniel] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Roach, Brian; Mathalon, Daniel] San Francisco VA Med Ctr, Mental Hlth Serv Line, San Francisco, CA USA. [D'Souza, Deepak Cyril; Fridberg, Daniel J.; Skosnik, Patrick D.; Williams, Ashley; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Sewell, R. Andrew; Ranganathan, Mohini] VA Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT 06516 USA. RP D'Souza, DC (reprint author), VA Connecticut Healthcare Syst, Psychiat Serv, 116A,950 Campbell Ave, West Haven, CT 06516 USA. EM deepak.dsouza@yale.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU Department of Veterans Affairs; National Institute of Mental Health; National Institute of Drug Abuse [R21 DA020750]; National Institute of Alcoholism and Alcohol Abuse (NIAAA); Yale Center for Clinical Investigation (YCCI); NARSAD; AstraZeneca, Inc; Pfizer, Inc.; Abbott Laboratories; Eli Lilly; Organon; Pfizer; Sanofi; Astra Zeneca FX We acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse (NIAAA), and (5) the Yale Center for Clinical Investigation (YCCI). This research project was funded in part by grants from NIDA (R21 DA020750 to DCD) and a NARSAD Young Investigator Award to PDS. We also thank Angelina Genovese, RNC, MBA; Michelle San Pedro, RN; Elizabeth O'Donnell, RN; Brenda Breault, RN, BSN; Sonah Yoo, RPh; Rachel Galvan, RPh; and Willie Ford of the Neurobiological Studies Unit at the VA Connecticut Healthcare System, West Haven Campus for their central contributions to the success of this project.; Daniel Fridberg, Patrick Skosnik, Ashley Williams, Brian Roach, Nagendra Singh, Michelle Carbuto, Jacqueline Elander, Ashley Schnakenberg, Brian Pittman, and Andrew Sewell report no financial relationships with commercial interests. Dr Mathalon reports research funding from AstraZeneca, Inc, consulting fees from Pfizer, Inc., and that his name is included under a provisional patent titled 'A non-invasive biomarker of human cortical plasticity and cognition', USPTO serial number 61/140 833. Mohini Ranganathan has in the past 3 years or currently receives research grant support administered through Yale University School of Medicine from Eli Lilly. Deepak Cyril D'Souza has in the past 3 years or currently receives research grant support administered through Yale University School of Medicine from Astra Zeneca, Abbott Laboratories, Eli Lilly, Organon, Pfizer, and Sanofi; he is a consultant for Bristol Meyers Squibb. NR 93 TC 35 Z9 36 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2012 VL 37 IS 7 BP 1632 EP 1646 DI 10.1038/npp.2012.8 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 942LO UT WOS:000304045700008 PM 22334121 ER PT J AU Lotfipour, S Mandelkern, M Alvarez-Estrada, M Brody, AL AF Lotfipour, Shahrdad Mandelkern, Mark Alvarez-Estrada, Miguel Brody, Arthur L. TI A Single Administration of Low-Dose Varenicline Saturates alpha 4 beta 2* Nicotinic Acetylcholine Receptors in the Human Brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cigarettes; nicotinic receptors; addiction; varenicline; withdrawal; thalamus ID PARTIAL AGONIST VARENICLINE; GENETICALLY-MODIFIED MICE; IN-VIVO; WITHDRAWAL SYMPTOMS; TOBACCO WITHDRAWAL; BINDING-PROPERTIES; SMOKING-CESSATION; PRENATAL-EXPOSURE; MATERNAL-SMOKING; DRUG-USE AB The primary objective of this project was to determine the alpha 4 beta 2* nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low dose of varenicline (0.5 mg), and to explore the relationship between receptor occupancy by varenicline and tobacco withdrawal symptoms (*denoting other putative nAChR subunits). Otherwise healthy smokers (n = 9) underwent two positron emission tomography (PET) sessions with the selective alpha 4 beta 2* radioligand 2-FA. For the PET sessions, participants received either a low dose of varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before imaging. For both sessions, participants received bolus plus continuous infusions of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady state, smoked to satiety, and were scanned for 2 more hours. We estimated the fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the corresponding varenicline dissociation constant (K-V), along with the effect of low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating scales. The data are compatible with 100% occupancy of alpha 4 beta 2* nAChRs by a single dose of varenicline, with a 90% lower confidence limit of 89% occupancy for the thalamus and brainstem. The corresponding 90% upper limit on effective K-V with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not low-dose varenicline, significantly reduced withdrawal symptoms. Our findings demonstrate that low-dose varenicline results in saturation of alpha 4 beta 2* nAChRs in the thalamus and brainstem without reducing withdrawal symptoms. Neuropsychopharmacology (2012) 37, 1738-1748; doi:10.1038/npp.2012.20; published online 7 March 2012 C1 [Lotfipour, Shahrdad] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, MacDonald Res Labs, Los Angeles, CA 90095 USA. [Lotfipour, Shahrdad; Brody, Arthur L.] Univ Calif Los Angeles, Hatos Ctr Neuropharmacol, Semel Inst, Los Angeles, CA 90095 USA. [Lotfipour, Shahrdad; Mandelkern, Mark; Alvarez-Estrada, Miguel; Brody, Arthur L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Lotfipour, S (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, MacDonald Res Labs, 675 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM shahrdad@ucla.edu RI Lotfipour, Shahrdad/K-8335-2014 OI Lotfipour, Shahrdad/0000-0002-2425-1096 FU Pfizer Pharmaceutical Corporation [WS653344]; NIMH [MH17140]; NIDA [R01 DA20872]; Richard Metzner Chair in Clinical Neuropharmacology FX We thank Karen Ta, Jaime La Charite, Betram Nweke, Stuart Mirell, Van Cayetano, Chien Nguyen, Judah Farahi, Andrew Leuchter, Hans Rollema, Maziar Maghsoodnia, Alison Curtin, Ron Waldorf, Diep Seversen, and Josephine Ribe for their assistance on the study. This work was funded by Pfizer Pharmaceutical Corporation (Grant number: WS653344) (SL) and, in part, by T-32 NIMH post-doctoral fellowship (MH17140) (SL), NIDA (R01 DA20872) (ALB), and the Richard Metzner Chair in Clinical Neuropharmacology (ALB). NR 52 TC 13 Z9 13 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2012 VL 37 IS 7 BP 1738 EP 1748 DI 10.1038/npp.2012.20 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 942LO UT WOS:000304045700018 PM 22395733 ER PT J AU Paik, JM Farwell, WR Taylor, EN AF Paik, J. M. Farwell, W. R. Taylor, E. N. TI Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE CDC; Centers for Disease Control and Prevention; National Health and Nutrition Examination Survey; NHANES; Parathyroid hormone ID AGE-RELATED-CHANGES; INTESTINAL CALCIUM-ABSORPTION; CHRONIC KIDNEY-DISEASE; D-ENDOCRINE SYSTEM; VITAMIN-D; URIC-ACID; INCIDENT HYPERTENSION; POSTMENOPAUSAL WOMEN; RACIAL-DIFFERENCES; BLOOD-PRESSURE AB Many determinants of parathyroid hormone (PTH) are unknown. In the National Health and Nutrition Examination Survey (NHANES), numerous factors not classically associated with calcium-phosphorus homeostasis, such as uric acid and smoking, are independently associated with PTH in adults without chronic kidney disease. Associations between serum phosphorus and PTH may vary by race. Although PTH may be an important biomarker for osteoporosis and cardiovascular disease, many determinants of PTH are unknown. We investigated associations between demographic, dietary, and serum factors and PTH level. We studied 4,026 white, 1,792 black, and 1,834 Mexican-American adult participants without chronic kidney disease from the 2003-2004 and 2005-2006 NHANES. The mean serum PTH level was 38.3 pg/ml for whites, 42.6 pg/ml for blacks, and 41.3 pg/ml for Mexican-Americans. After adjusting for diet, body mass index, serum levels of calcium, phosphorus, 25-hydroxyvitamin D, creatinine, and other factors, smokers compared to non-smokers had lower PTH, ranging from -4.2 pg/ml (95% confidence interval (CI) -7.3 to -1.1) in Mexican-Americans to -6.1 pg/ml (95% CI -8.7 to -3.5) in blacks. After multivariate adjustment, PTH was higher in females compared to males, ranging from 1.1 pg/ml (95% CI -1.2 to 3.4) in Mexican-Americans to 4.5 pg/ml (95% CI 1.9 to 7.0) in blacks, and in older (> 60 years) compared to younger participants (< 30 years), ranging from 3.7 pg/ml (95% CI 1.3 to 6.1) in Mexican-Americans to 8.0 pg/ml (95% CI 5.4 to 10.7) in blacks. Higher uric acid was associated with higher PTH. In whites only, lower serum phosphorus and lower serum retinol were associated with higher PTH. Numerous factors not classically associated with calcium-phosphorus homeostasis are independently associated with PTH and should be considered in future studies of PTH and chronic disease. Additional research is needed to elucidate mechanisms underlying identified associations with PTH and to explore possible racial differences in phosphorus handling. C1 [Paik, J. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal,Dept Med, Boston, MA 02115 USA. [Paik, J. M.; Taylor, E. N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Farwell, W. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. [Farwell, W. R.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Taylor, E. N.] Maine Med Ctr, Div Nephrol & Transplantat, Portland, ME 04102 USA. RP Paik, JM (reprint author), Channing Lab 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM jmpaik@partners.org FU Department of Veterans Affairs Office of Research Development; National Institutes of Health [DK084707, DK007527, R01 HL092947] FX Work on this study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research Development. Additional research support was obtained from grants DK084707, DK007527, and R01 HL092947 from the National Institutes of Health. NR 58 TC 13 Z9 13 U1 0 U2 7 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JUN PY 2012 VL 23 IS 6 BP 1727 EP 1736 DI 10.1007/s00198-011-1776-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943ZN UT WOS:000304167300010 PM 21932115 ER PT J AU Jung, M AF Jung, Minsoo TI Immigrant Workers' Knowledge of HIV/AIDS and Their Sexual Risk Behaviors: A Respondent-Driven Sampling Survey in South Korea SO SEXUALITY AND DISABILITY LA English DT Article DE Sexual risk behavior; Immigrant groups; HIV knowledge; Respondent-driven sampling; South Korea ID HIV RISK; AIDS; MEN AB As the labor market goes global, immigrant workers are becoming important around the world. However, little research has focused on the characteristics of their sex behaviors. This study examines foreign employees in Korea in order to investigate their understanding of HIV and sexual risk behaviors. The sample ( = 547) was formed from migrant workers in the industrial complex in Ansan district, which depends highly on foreigners as its labor source. Logistic regression, analysis revealed that 36.0% of the respondents were engaged in more than one sexual risk behavior. Those who knew someone infected with HIV (OR = 2.583) and Thai respondents (OR = 3.007) showed high sexual risk behaviors, while married (OR = 0.182) and Korean Chinese (OR = 0.280) workers showed low sexual risk behaviors. Those who had a wealth of knowledge about HIV took a less discriminatory position against the person who had infected them, but this had no statistical effects over the sexual risk behaviors. C1 [Jung, Minsoo] Korea Univ, Dept Healthcare Management, Seoul 136703, South Korea. [Jung, Minsoo] Korea Univ, Hlth Sci Res Inst, Seoul 136703, South Korea. [Jung, Minsoo] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jung, M (reprint author), Korea Univ, Dept Healthcare Management, San 1, Seoul 136703, South Korea. EM mins.jung@gmail.com OI Jung, Minsoo/0000-0003-3317-6507 NR 25 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD JUN PY 2012 VL 30 IS 2 BP 199 EP 208 DI 10.1007/s11195-011-9245-1 PG 10 WC Rehabilitation SC Rehabilitation GA 943VZ UT WOS:000304155100008 ER PT J AU Zinzow, HM Resnick, HS McCauley, JL Amstadter, AB Ruggiero, KJ Kilpatrick, DG AF Zinzow, Heidi M. Resnick, Heidi S. McCauley, Jenna L. Amstadter, Ananda B. Ruggiero, Kenneth J. Kilpatrick, Dean G. TI Prevalence and risk of psychiatric disorders as a function of variant rape histories: results from a national survey of women SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Rape; Sexual assault; Posttraumatic stress disorder; Depression; Alcohol abuse; Drug abuse; Comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT; INCAPACITATED RAPE; MENTAL-HEALTH; SUBSTANCE USE; ALCOHOL; SAMPLE; COMMUNITY; VIOLENCE; COMORBIDITY AB Rape is an established risk factor for mental health disorders, such as posttraumatic stress disorder (PTSD), major depressive episodes (MDE), and substance use disorders. The majority of studies have not differentiated substance-involved rape or examined comorbid diagnoses among victims. Therefore, the aim of the present study was to estimate the prevalence of common trauma-related psychiatric disorders (and their comorbidity) in a national sample of women, with an emphasis on distinguishing between rape tactics. A secondary objective was to estimate the risk for psychiatric disorders among victims of variant rape tactics, in comparison to non-victims. A nationally representative population-based sample of 3,001 non-institutionalized, civilian, English or Spanish speaking women (aged 18-86 years) participated in a structured telephone interview assessing rape history and DSM-IV criteria for PTSD, MDE, alcohol abuse (AA), and drug abuse (DA). Descriptive statistics and multivariate logistic regression analyses were employed. Women with rape histories involving both substance facilitation and forcible tactics reported the highest current prevalence of PTSD (36%), MDE (36%), and AA (20%). Multivariate models demonstrated that this victim group was also at highest risk for psychiatric disorders, after controlling for demographics and childhood and multiple victimization history. Women with substance-facilitated rapes reported higher prevalence of substance abuse in comparison to women with forcible rape histories. Comorbidity between PTSD and other psychiatric disorders was higher among rape victims in comparison to non-rape victims. Researchers and clinicians should assess substance-facilitated rape tactics and attend to comorbidity among rape victims. Empirically supported treatments are needed to address the complex presentations observed among women with variant rape histories. C1 [Zinzow, Heidi M.] Clemson Univ, Dept Psychol, Clemson, SC 29634 USA. [Resnick, Heidi S.; McCauley, Jenna L.; Amstadter, Ananda B.; Ruggiero, Kenneth J.; Kilpatrick, Dean G.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Zinzow, HM (reprint author), Clemson Univ, Dept Psychol, 418 Brackett Hall, Clemson, SC 29634 USA. EM hzinzow@clemson.edu FU National Institute of Justice [2005-WG-BX-0006]; NIDA [1R01DA023099-01A2] FX The research design and data collection were supported by National Institute of Justice Grant #2005-WG-BX-0006 (principal investigator: Dean G. Kilpatrick). Support for manuscript preparation was provided by NIDA 1R01DA023099-01A2 (principal investigator: Heidi Resnick). Views expressed in this article do not necessarily represent those of the agencies supporting this research. NR 27 TC 19 Z9 19 U1 7 U2 23 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JUN PY 2012 VL 47 IS 6 BP 893 EP 902 DI 10.1007/s00127-011-0397-1 PG 10 WC Psychiatry SC Psychiatry GA 944AT UT WOS:000304171300006 PM 21603967 ER PT J AU Lee, C Fotovati, A Triscott, J Chen, J Venugopal, C Singhal, A Dunham, C Kerr, JM Verreault, M Yip, S Wakimoto, H Jones, C Jayanthan, A Narendran, A Singh, SK Dunn, SE AF Lee, Cathy Fotovati, Abbas Triscott, Joanna Chen, James Venugopal, Chitra Singhal, Ash Dunham, Christopher Kerr, John M. Verreault, Maite Yip, Stephen Wakimoto, Hiroaki Jones, Chris Jayanthan, Aarthi Narendran, Aru Singh, Sheila K. Dunn, Sandra E. TI Polo-Like Kinase 1 Inhibition Kills Glioblastoma Multiforme Brain Tumor Cells in Part Through Loss of SOX2 and Delays Tumor Progression in Mice SO STEM CELLS LA English DT Article DE Apoptosis; Cancer stem cells; Cancer; Glioma ID HERPES-SIMPLEX-VIRUS; CANCER STEM-CELLS; BIPOLAR SPINDLE FORMATION; ACUTE MYELOID-LEUKEMIA; ADVANCED SOLID TUMORS; INITIATING CELLS; BREAST-CANCER; PHASE-I; GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE AB Glioblastoma multiforme (GBM) ranks among the deadliest types of cancer and given these new therapies are urgently needed. To identify molecular targets, we queried a microarray profiling 467 human GBMs and discovered that polo-like kinase 1 (PLK1) was highly expressed in these tumors and that it clustered with the proliferative subtype. Patients with PLK1-high tumors were more likely to die from their disease suggesting that current therapies are inactive against such tumors. This prompted us to examine its expression in brain tumor initiating cells (BTICs) given their association with treatment failure. BTICs isolated from patients expressed 110-470 times more PLK1 than normal human astrocytes. Moreover, BTICs rely on PLK1 for survival because the PLK1 inhibitor BI2536 inhibited their growth in tumorsphere cultures. PLK1 inhibition suppressed growth, caused G2/M arrest, induced apoptosis, and reduced the expression of SOX2, a marker of neural stem cells, in SF188 cells. Consistent with SOX2 inhibition, the loss of PLK1 activity caused the cells to differentiate based on elevated levels of glial fibrillary acidic protein and changes in cellular morphology. We then knocked glial fibrillary acidic protein (GFAP) down SOX2 with siRNA and showed that it too inhibited cell growth and induced cell death. Likewise, in U251 cells, PLK1 inhibition suppressed cell growth, downregulated SOX2, and induced cell death. Furthermore, BI2536 delayed tumor growth of U251 cells in an orthotopic brain tumor model, demonstrating that the drug is active against GBM. In conclusion, PLK1 level is elevated in GBM and its inhibition restricts the growth of brain cancer cells. STEM CELLS2012;30:10641075 C1 [Dunn, Sandra E.] Univ British Columbia, Dept Paediat, Dept Expt Med, Vancouver, BC V5Z 4H4, Canada. [Venugopal, Chitra; Singh, Sheila K.] McMaster Univ, Dept Surg, Div Neurol Surg, Fac Hlth Sci, Hamilton, ON L8S 4L8, Canada. [Singhal, Ash; Kerr, John M.] BC Childrens Hosp, Dept Surg, Div Pediat Neurosurg, Vancouver, BC, Canada. [Dunham, Christopher] BC Childrens Hosp, Dept Pathol & Lab Med, Div Anat Patol, Vancouver, BC, Canada. [Verreault, Maite] Univ British Columbia, Dept Expt Therapeut, Div Pharmacol & Toxicol, BC Canc Res Ctr, Vancouver, BC, Canada. [Yip, Stephen] Ctr Translat & Appl Gen, BC Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC, Canada. [Wakimoto, Hiroaki] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Simches Res Ctr, Boston, MA 02114 USA. [Jones, Chris] Royal Marsden Hosp, Inst Canc Res, Surrey, England. [Jayanthan, Aarthi; Narendran, Aru] Alberta Childrens Prov Gen Hosp, POETIC Lab Pre Clin & Drug Discovery Studies, Calgary, AB, Canada. RP Dunn, SE (reprint author), Univ British Columbia, Dept Paediat, Dept Expt Med, Room 3082,950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM sedunn@mail.ubc OI Dunham, Christopher/0000-0002-6244-0584 FU Michael Smith Foundation for Health Research; Hannah's Heroes Foundation; C17 Research Network; STEMCELL Technologies; NHS FX This work was supported by the Michael Smith Foundation for Health Research and Hannah's Heroes Foundation (SED and CL). It was also funded by the C17 Research Network (SED and AN). We are also grateful to STEMCELL Technologies for their kind support. CJ acknowledges NHS funding to the NIHR Bio-medical Research Centre. We also thank our collaborators Dr. Brent Reynolds as well as Dr. Paul Steinbok, Dr. Doug Cochrane, Dr. Rod Rassekh, Dr. Vesna Popovska, and Dr. Glenda Hendson at the B. C. Children's Hospital for helping us obtain patient tumor specimens and for their contribution to the study. NR 88 TC 31 Z9 31 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JUN PY 2012 VL 30 IS 6 BP 1064 EP 1075 DI 10.1002/stem.1081 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 942YJ UT WOS:000304087300004 PM 22415968 ER PT J AU Steere, A AF Steere, A. TI LYME DISEASE - OLD AND NEW INSIGHTS SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Steere, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2012 VL 71 SU 3 BP 43 EP 43 PG 1 WC Rheumatology SC Rheumatology GA V31QQ UT WOS:000208898500178 ER PT J AU Rauen, T Grammatikos, A Hedrich, CM Kyttaris, VC Tenbrock, K Raffetseder, U Floege, J Tsokos, GC AF Rauen, T. Grammatikos, A. Hedrich, C. M. Kyttaris, V. C. Tenbrock, K. Raffetseder, U. Floege, J. Tsokos, G. C. TI CAMP RESPONSIVE ELEMENT MODULATOR (CREM) ALPHA CONTRIBUTES TO DECREASED NOTCH-1 EXPRESSION IN T CELLS FROM PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Rauen, T.; Raffetseder, U.; Floege, J.] Rhein Westfal TH Aachen, Dept Nephrol & Clin Immunol, Aachen, Germany. [Grammatikos, A.; Hedrich, C. M.; Kyttaris, V. C.; Tsokos, G. C.] Harvard Univ, Sch Med, Bidmc, Div Rheumatol, Boston, MA USA. [Tenbrock, K.] Rhein Westfal TH Aachen, Dept Pediat, Aachen, Germany. NR 3 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2012 VL 71 SU 3 BP 155 EP 155 PG 1 WC Rheumatology SC Rheumatology GA V31QQ UT WOS:000208898500493 ER PT J AU Krasoudaki, E Stagakis, E Loupasakis, K Papagianni, A Alexopoulos, E Bertsias, G Iliopoulos, D Boumpas, D AF Krasoudaki, E. Stagakis, E. Loupasakis, K. Papagianni, A. Alexopoulos, E. Bertsias, G. Iliopoulos, D. Boumpas, D. TI MICRORNA ANALYSIS OF HUMAN LUPUS NEPHRITIS: EVIDENCE FOR MODULATION OF KALLIKREIN 4 BY MIR-422A SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Krasoudaki, E.; Stagakis, E.; Bertsias, G.; Boumpas, D.] Univ Crete, Lab Autoimmun & Inflammat, Iraklion, Greece. [Loupasakis, K.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Papagianni, A.; Alexopoulos, E.] Aristotle Univ Thessaloniki, Dept Nephrol, GR-54006 Thessaloniki, Greece. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2012 VL 71 SU 3 BP 472 EP 473 PG 2 WC Rheumatology SC Rheumatology GA V31QQ UT WOS:000208898502356 ER PT J AU Singh, JA Wells, GA Christensen, R Tanjong, E MacDonald, J Tugwell, P Buchbinder, R AF Singh, J. A. Wells, G. A. Christensen, R. Tanjong, E. MacDonald, J. Tugwell, P. Buchbinder, R. CA Biol Safety Study Grp TI ADVERSE EFFECTS OF BIOLOGICS: A NETWORK META-ANALYSIS AND COCHRANE OVERVIEW SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Wells, G. A.] McMaster Univ, Ottawa, ON, Canada. [Christensen, R.] Univ Denmark, Copenhagen, Denmark. [Tanjong, E.; Tugwell, P.] Univ Ottawa, Montreal, PQ, Canada. [MacDonald, J.] Univ Washington, Seattle, WA 98195 USA. [Buchbinder, R.] Monash Univ, Monash, Australia. NR 0 TC 0 Z9 0 U1 2 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2012 VL 71 SU 3 BP 628 EP 628 PG 1 WC Rheumatology SC Rheumatology GA V31QQ UT WOS:000208898503315 ER PT J AU McDermott, S Guimaraes, AR AF McDermott, Shaunagh Guimaraes, Alexander R. TI Magnetic Nanoparticles in the Imaging of Tumor Angiogenesis SO APPLIED SCIENCES-BASEL LA English DT Review DE angiogenesis; ultrasmall superparamagnetic iron oxide; magnetic resonance imaging AB Angiogenesis, the growth of new capillary blood vessels, is central to the growth of tumors. Non-invasive imaging of tumor angiogenesis will allow for earlier detection of tumors and also the development of surrogate markers for assessing response to treatment. Steady state magnetic resonance imaging with magnetic nanoparticles is one method to assess angiogenesis. In this article we explain the theory behind steady state magnetic resonance imaging and review the available literature. C1 [McDermott, Shaunagh; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP McDermott, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM smcdermott1@partners.org; aguimaraes@mgh.harvard.edu NR 42 TC 3 Z9 3 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2076-3417 J9 APPL SCI-BASEL JI Appl. Sci.-Basel PD JUN PY 2012 VL 2 IS 2 BP 525 EP 534 DI 10.3390/app2020525 PG 10 WC Chemistry, Multidisciplinary; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Materials Science; Physics GA V36XK UT WOS:000209240800019 ER PT J AU von Recum, J Matschke, S Jupiter, JB Ring, D Souer, JS Huber, M Audige, L AF von Recum, J. Matschke, S. Jupiter, J. B. Ring, D. Souer, J-S. Huber, M. Audige, L. TI Characteristics of two different locking compression plates in the volar fixation of complex articular distal radius fractures SO BONE & JOINT RESEARCH LA English DT Article DE Distal radius fracture; Open reduction and internal fixation; ORIF; Locking compression plate; LCP; Comparative analysis AB Objectives To investigate the differences of open reduction and internal fixation (ORIF) of complex AO Type C distal radius fractures between two different models of a single implant type. Methods A total of 136 patients who received either a 2.4 mm (n = 61) or 3.5 mm (n = 75) distal radius locking compression plate (LCP DR) using a volar approach were followed over two years. The main outcome measurements included motion, grip strength, pain, and the scores of Gartland and Werley, the Short-Form 36 (SF-36) and the Disabilities of the Arm, Shoulder, and Hand (DASH). Differences between the treatment groups were evaluated using regression analysis and the likelihood ratio test with significance based on the Bonferroni corrected p-value of < 0.003. Results The groups were similar with respect to baseline and injury characteristics as well as general surgical details. The risk of experiencing a complication after ORIF with a LCP DR 2.4 mm was 18% (n = 11) compared with 11% (n = 8) after receiving a LCP DR 3.5 mm (p = 0.45). Wrist function was also similar between the cohorts based on the mean ranges of movement (all p > 0.052) and grip strength measurements relative to the contralateral healthy side (p = 0.583). In addition, DASH and SF-36 component scores as well as pain were not significantly different between the treatment groups throughout the two-year period (all p = 0.005). No patient from either treatment group had a step-off > 2 mm. Conclusions Differences in plate design do not influence the overall final outcome of fracture fixation using LCP. C1 [Matschke, S.] BG Trauma Ctr Ludwigshafen, D-67071 Ludwigshafen, Germany. [Jupiter, J. B.; Ring, D.; Souer, J-S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huber, M.; Audige, L.] AO Clin Invest & Documentat, CH-8600 Dubendorf, Switzerland. RP von Recum, J (reprint author), Dept Knee Foot & Ankle Surg, Los Angeles, CA 90211 USA. EM Jan.von-Recum@bgu-ludwigshafen.de RI AOCID, AO Foundation/R-6455-2016 FU AO Foundation FX The work presented in this manuscript was supported by the AO Foundation NR 25 TC 4 Z9 4 U1 0 U2 1 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2046-3758 J9 BONE JOINT RES JI Bone Jt. Res. PD JUN PY 2012 VL 1 IS 6 BP 111 EP 117 DI 10.1302/2046-3758.16.2000008 PG 7 WC Cell & Tissue Engineering; Orthopedics SC Cell Biology; Orthopedics GA V35HA UT WOS:000209139800003 PM 23610680 ER PT J AU Maleki, N Becerra, L Brawn, J Bigal, M Burstein, R Borsook, D AF Maleki, Nasim Becerra, Lino Brawn, Jennifer Bigal, Marcelo Burstein, Rami Borsook, David TI Concurrent functional and structural cortical alterations in migraine SO CEPHALALGIA LA English DT Article DE Headache; pain; fMRI; functional connectivity; morphometry; somatosensory cortex; insula; cingulate cortex; temporal pole ID HUMAN CEREBRAL-CORTEX; PRIMARY SOMATOSENSORY CORTEX; VOXEL-BASED MORPHOMETRY; REGIONAL PAIN SYNDROME; GREY-MATTER CHANGES; HUMAN BRAIN; GEOMETRICALLY ACCURATE; SYNAPTIC PLASTICITY; PREFRONTAL CORTEX; NEUROPATHIC PAIN AB Aim: Various animal and human studies have contributed to the idea of cortical structural-functional alterations in migraine. Defining concurrent cortical alterations may provide specific insights into the unfolding adaptive or maladaptive changes taking place in cortex in migraine. Methods: From a group of 60 episodic migraineurs, 20 were recruited to the study. Using high-resolution magnetic resonance imaging, structural and functional cortical measures were compared in migraineurs who experienced increased frequency of attacks (HF; 8-14 days/month; n=10), to those who experienced less frequent migraine attacks (LF;<2 days/month; n=10), and to healthy controls (HC; n=20). Results: Parallel structural and functional differences were found as follows: (i) HF patients showed higher thickness in the area representing the face in the post-central gyrus, which correlated with the observed stronger functional activation, suggesting adaptation to repeated sensory drive; (ii) smaller cortical volume was observed in the cingulate cortex that correlated with lower activation in the HF group; and (iii) similarly significant structural and functional differences (HF>LF) were observed in the insula that may reflect potential alteration in affective processing. Conclusion: These results suggest differential response patterns in the sensory vs. affective processing regions in the brain that may be an adaptive response to repeated migraine attacks. C1 [Becerra, Lino; Borsook, David] Harvard Univ, McLean Hosp, PAIN Grp, Brain Imaging Ctr,Med Sch,Dept Psychiat, Belmont, MA 02478 USA. [Maleki, Nasim; Brawn, Jennifer] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Belmont, MA 02478 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Belmont, MA 02478 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Belmont, MA 02478 USA. [Bigal, Marcelo] Merck & Co Inc, Merck Investigator Studies Program, Whitehouse Stn, NJ USA. [Bigal, Marcelo] Merck & Co Inc, Sci Educ Grp, Merck Res Labs, Whitehouse Stn, NJ USA. [Bigal, Marcelo] Albert Einstein Coll Med, Dept Neurol, New York, NY USA. [Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Belmont, MA 02478 USA. RP Borsook, D (reprint author), Harvard Univ, McLean Hosp, PAIN Grp, Brain Imaging Ctr,Med Sch,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM dborsook@partners.org FU NIH [K24 NS064050, R01 NS056195, R01-NS073997]; Merck and Co. FX The work was supported by grants from NIH (K24 NS064050 (NINDS), R01 NS056195 (NINDS), and R01-NS073997 (NINDS) to DB) (data collection) and an Investigator Initiated Grant from Merck and Co. (data analysis). NR 68 TC 61 Z9 63 U1 1 U2 12 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2012 VL 32 IS 8 BP 607 EP 620 DI 10.1177/0333102412445622 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 959XS UT WOS:000305352100005 PM 22623760 ER PT J AU Certain, L Schuetz, P AF Certain, Laura Schuetz, Philipp TI The Role of Procalcitonin in Respiratory Infections SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Procalcitonin; Respiratory infection; Antibiotic stewardship; Biomarker ID COMMUNITY-ACQUIRED PNEUMONIA; C-REACTIVE PROTEIN; VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED-CONTROLLED-TRIALS; CRITICALLY-ILL PATIENTS; SERUM PROCALCITONIN; ANTIBIOTIC-THERAPY; TRACT INFECTIONS AB Accurate diagnosis, risk stratification, and decisions about the need for and optimal duration of antibiotic therapy are cornerstones of the management of patients with respiratory infections. A growing body of evidence supports the use of procalcitonin, a marker of bacterial infection, in addition to conventional clinical parameters to improve diagnostic and prognostic assessment in patients with suspicion of respiratory infections. In addition, several randomized controlled trials indicate that procalcitonin may be used for clinical decision making about initiation and optimal duration of antibiotic therapy. For patients with respiratory infections, procalcitonin-guided antibiotic therapy resulted in less antibiotic use without any apparent adverse patient outcome. For other infections outcome studies are currently lacking. This review summarizes the results of recent investigations of procalcitonin in respiratory infections to provide physicians an overview of the utility and limitations of procalcitonin when used for bedside decision making. C1 [Certain, Laura] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schuetz, Philipp] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Schuetz, P (reprint author), Harvard Univ, Sch Publ Hlth, 667 Huntington Ave, Boston, MA 02115 USA. EM Schuetzph@gmail.com OI schuetz, philipp/0000-0001-6400-4949 FU Swiss Foundation for Grants in Biology and Medicine (Schweizerische Stiftung fur medizinisch-biologische Stipendien, SSMBS [PASMP3127684/1]; BRAHMS Inc and Biomerieux FX Dr. Schuetz was supported by a research grant from the Swiss Foundation for Grants in Biology and Medicine (Schweizerische Stiftung fur medizinisch-biologische Stipendien, SSMBS, PASMP3127684/1) and reports receiving support from BRAHMS Inc and Biomerieux to attend meetings and fulfill speaking engagements. Dr. Certain reports no conflict of interest. NR 88 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD JUN PY 2012 VL 14 IS 3 BP 308 EP 316 DI 10.1007/s11908-012-0249-5 PG 9 WC Infectious Diseases SC Infectious Diseases GA V32XE UT WOS:000208983100011 PM 22382693 ER PT J AU El Nawawi, NM Balboni, MJ Balboni, TA AF El Nawawi, Nora M. Balboni, Michael J. Balboni, Tracy A. TI Palliative care and spiritual care: the crucial role of spiritual care in the care of patients with advanced illness SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE LA English DT Review DE end of life; palliative care; religion; spiritual care; spirituality AB Purpose of review Within the hospice and palliative care movement, patients' religion/spirituality (R/S) has been a core component of care incorporated within international and US palliative care guidelines. However, as the discipline of palliative care has been incorporated into the larger biomedical community, the inclusion of spiritual care has become controversial. This review summarizes key empirical research at the intersection of palliative care and R/S in order to assess its validity as a domain of end-of-life care. Recent findings Recent research shows that R/S and spiritual care are important components to the care of patients facing advanced illness. Patients - particularly ethnic minorities - rely upon R/S as an important means to interpret and cope with illness. Studies suggest that R/S plays an important role in coping with disease-related symptoms, improves quality of life, and impacts medical decision-making near death. Patients largely desire medical caregivers to take an active role in providing spiritual care, and patients likewise frequently experience multiple spiritual needs arising in the face of life-threatening illness. Summary Despite an empirical evidence for spiritual care as part of palliative care, R/S remains insufficiently addressed by the medical system. Further research is required in order to more clearly identify the roles of healthcare providers and standardize the provision of spiritual care within palliative care. C1 [El Nawawi, Nora M.; Balboni, Michael J.; Balboni, Tracy A.] Dana Farber Canc Inst, Ctr Psychosocial Oncol & Palliat Care Res, Boston, MA 02115 USA. [Balboni, Michael J.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Balboni, Michael J.] Harvard Univ, Sch Divin, Cambridge, MA 02138 USA. [Balboni, Tracy A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Balboni, TA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana 1101,450 Brookline Ave, Boston, MA 02115 USA. EM TBalboni@LROC.Harvard.edu NR 33 TC 25 Z9 26 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1751-4258 EI 1751-4266 J9 CURR OPIN SUPPORT PA JI Curr. Opin Support Palliat. Car. PD JUN PY 2012 VL 6 IS 2 BP 269 EP 274 DI 10.1097/SPC.0b013e3283530d13 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA V32OR UT WOS:000208961000024 PM 22469668 ER PT J AU Bikle, DD AF Bikle, Daniel D. TI Vitamin D and Bone SO CURRENT OSTEOPOROSIS REPORTS LA English DT Article DE Vitamin D; Vitamin D receptor; CYP27B1; 25hydroxyvitamin; 1,25 dihydroxyvitamin D; 24,25 dihydroxyvitamin D; Bone; Chondrocytes; Osteoblasts; Osteoclasts AB All cells comprising the skeleton-chondrocytes, osteoblasts, and osteoclasts-contain both the vitamin D receptor and the enzyme CYP27B1 required for producing the active metabolite of vitamin D, 1,25 dihydroxyvitamin D. Direct effects of 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D on these bone cells have been demonstrated. However, the major skeletal manifestations of vitamin D deficiency or mutations in the vitamin D receptor and CYP27B1, namely rickets and osteomalacia, can be corrected by increasing the intestinal absorption of calcium and phosphate, indicating the importance of indirect effects. On the other hand, these dietary manipulations do not reverse defects in osteoblast or osteoclast function that lead to osteopenic bone. This review discusses the relative importance of the direct versus indirect actions of vitamin D on bone, and provides guidelines for the clinical use of vitamin D to prevent/treat bone loss and fractures. C1 [Bikle, Daniel D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bikle, DD (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111N, San Francisco, CA 94121 USA. EM Daniel.bikle@ucsf.edu FU National Institutes of Health [RO1 DK054793, AR055924, AR050023] FX D.D. Bikle: has received grant support from the National Institutes of Health (RO1 DK054793, AR055924, and AR050023); and receives loyalties from Lange textbook chapter. NR 86 TC 35 Z9 37 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA EI 1544-2241 J9 CURR OSTEOPOROS REP JI Curr. Osteoporos. Rep. PD JUN PY 2012 VL 10 IS 2 BP 151 EP 159 DI 10.1007/s11914-012-0098-z PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V35YS UT WOS:000209181600007 PM 22544628 ER PT J AU Papisov, MI Belov, V Fischman, AJ Belova, E Titus, J Gagne, M Gillooly, C AF Papisov, Mikhail I. Belov, V. Fischman, A. J. Belova, E. Titus, J. Gagne, M. Gillooly, C. TI Delivery of proteins to CNS as seen and measured by positron emission tomography SO DRUG DELIVERY AND TRANSLATIONAL RESEARCH LA English DT Article DE PET Imaging; Pharmacokinetics; Biopharmaceuticals; Macromolecules; Brain; Central nervous system; Drug delivery; Iodine-124 AB Presently, there are no effective treatments for several diseases involving the central nervous system (CNS). While several novel molecular approaches are being developed, many of them require delivery of macromolecular or supramolecular agents to the CNS tissues protected by the blood-brain and blood-arachnoid barriers. A variety of approaches that are being developed for overcoming or bypassing the barriers are based on complex transfer processes. The delivery of biopharmaceuticals and other macromolecules and particulates to the CNS, especially through the leptomeningeal (intrathecal) route, includes a variety of stages, such as leptomeningeal propagation, drainage to the systemic circulation, and penetration into the CNS. The investigation of complex pharmacokinetics that includes convective, as well as diffusional and active transfer processes, greatly benefit from real-time non-invasive in vivo monitoring of the drug transport. Pharmacological positron emission tomography (PET) imaging, which enables such monitoring, plays an increasingly significant role in drug delivery and biopharmacology. PET is a powerful tool for quantitative in vivo tracking of molecules labeled with positron-emitting radionuclides. The high sensitivity, format, and accuracy of the data (similar to those of conventional tissue sampling biodistribution studies) make PET a readily adoptable pharmacological technique. In contrast to the conventional studies, PET also allows for longitudinal nonterminal same-animal studies. The latter may not only improve the data statistics, but also enable preclinical studies (especially in large and/or rare animals) not feasible under the conventional approach. This paper is intended to demonstrate the character of data that can be obtained by PET and to demonstrate how the main patterns of the leptomeningeal route pharmacokinetics can be investigated using this method. Examples of data processing are taken from our recent studies of five model proteins in rats and nonhuman primates. C1 [Papisov, Mikhail I.; Belov, V.; Belova, E.; Titus, J.; Gagne, M.; Gillooly, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papisov, Mikhail I.; Belov, V.; Fischman, A. J.; Belova, E.] Harvard Univ, Sch Med, Boston, MA USA. [Papisov, Mikhail I.; Belov, V.; Fischman, A. J.; Belova, E.] Shriners Hosp Children, Boston, MA USA. RP Papisov, MI (reprint author), Massachusetts Gen Hosp, Bartlett Hall 500R,55 Fruit St, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU NIH [R21 CA152384]; DoD [BC100684]; Shire HGT FX This work was supported by NIH grant R21 CA152384, DoD grant BC100684, and grants from Shire HGT. Shire HGT also provided model proteins and imaging equipment. NR 16 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2190-393X EI 2190-3948 J9 DRUG DELIV TRANSL RE JI Drug Deliv. Transl. Res. PD JUN PY 2012 VL 2 IS 3 SI SI BP 201 EP 209 DI 10.1007/s13346-012-0073-3 PG 9 WC Instruments & Instrumentation; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Instruments & Instrumentation; Research & Experimental Medicine; Pharmacology & Pharmacy GA V39PW UT WOS:000209423900007 PM 25786867 ER PT J AU Papisov, MI Belov, V Belova, E Fischman, AJ Fisher, R Wright, JL Gannon, KS Titus, J Gagne, M Gillooly, CA AF Papisov, Mikhail I. Belov, V. Belova, E. Fischman, A. J. Fisher, R. Wright, J. L. Gannon, K. S. Titus, J. Gagne, M. Gillooly, C. A. TI Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates SO DRUG DELIVERY AND TRANSLATIONAL RESEARCH LA English DT Article DE Bacteriophage M13, NPT002, PET imaging; Pharmacokinetics; Brain; Iodine-124 AB Presently, there are no effective treatments for conditions characterized by protein misfolding, such as Alzheimer's, Parkinson's, and other diseases involving CNS. Since misfolding occurs at the earliest stage of the disease, it is likely to be involved in subsequent pathological developments. It has been found that NPT002 (bacteriophage M13) directly dissociates aggregates of misfolded proteins that form amyloid, including amyloid-beta, tau and alpha-synuclein. For CNS applications, NPT002 requires delivery to the brain parenchyma, the target tissue. NPT002 is an elongated similar to 950 nm particle that cannot penetrate into the brain from the blood. Furthermore, phage particles, due to their size, cannot be effectively transported in vivo by diffusion. Considering the physiology of the leptomeningeal space, intrathecal administration appears to be a promising convection-driven avenue for NPT002 delivery. In this paper, we use positron emission tomography to investigate the transport of NPT002 in Macaca fascicularis. The data suggest that approximately 50 % of the administered dose can reach the cerebral leptomeningeal space after a single lumbar intrathecal injection. A biologically significant fraction of the phage then enters the brain, resulting in potentially therapeutic cortical and subcortical exposure. C1 [Papisov, Mikhail I.; Belov, V.; Belova, E.; Titus, J.; Gagne, M.; Gillooly, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papisov, Mikhail I.; Belov, V.; Belova, E.; Fischman, A. J.] Harvard Univ, Sch Med, Boston, MA USA. [Papisov, Mikhail I.; Belov, V.; Belova, E.; Fischman, A. J.] Shriners Hosp Children, Boston, MA USA. [Fisher, R.; Wright, J. L.; Gannon, K. S.] NeuroPhage Pharmaceut Inc, Cambridge, MA USA. RP Papisov, MI (reprint author), Massachusetts Gen Hosp, Bartlett Hall 500R,55 Fruit St, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU NeuroPhage Pharmaceuticals, Inc. [NPT001, NPT002] FX This work was supported by a grant from NeuroPhage Pharmaceuticals, Inc. NeuroPhage also provided the purified and formulated bacteriophage M13 preparations, NPT001 and NPT002. NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2190-393X EI 2190-3948 J9 DRUG DELIV TRANSL RE JI Drug Deliv. Transl. Res. PD JUN PY 2012 VL 2 IS 3 SI SI BP 210 EP 221 DI 10.1007/s13346-012-0074-2 PG 12 WC Instruments & Instrumentation; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Instruments & Instrumentation; Research & Experimental Medicine; Pharmacology & Pharmacy GA V39PW UT WOS:000209423900008 PM 25786868 ER PT J AU LeVarge, BL Channick, RN AF LeVarge, Barbara L. Channick, Richard N. TI Inhaled treprostinil for the treatment of pulmonary arterial hypertension SO EXPERT REVIEW OF RESPIRATORY MEDICINE LA English DT Article DE administration; analogs and derivatives; epoprostenol; inhalation; pulmonary arterial hypertension; pulmonary circulation; treprostinil ID CONTINUOUS INTRAVENOUS PROSTACYCLIN; CONTINUOUS SUBCUTANEOUS INFUSION; PLACEBO-CONTROLLED TRIAL; BLOOD-STREAM INFECTIONS; SMOOTH-MUSCLE-CELLS; DOUBLE-BLIND; BERAPROST SODIUM; RANDOMIZED-TRIAL; IV TREPROSTINIL; GAS-EXCHANGE AB Treprostinil is a prostacyclin derivative approved for the treatment of pulmonary arterial hypertension by intravenous, subcutaneous and inhalational administration. Unlike its precursor epoprostenol, treprostinil is chemically stable at room temperature and neutral pH, and its plasma half-life is longer. In addition to promoting smooth muscle relaxation in the pulmonary vasculature, treprostinil has suppressive effects on platelet aggregation, smooth muscle proliferation and inflammation. A Phase III study, investigating the addition of inhaled treprostinil to oral bosentan or sildenafil, confirmed significant improvements in exercise capacity and quality of life. This review examines the pharmacodynamics, pharmacokinetics, clinical efficacy and safety of inhaled treprostinil for use in pulmonary arterial hypertension. C1 [LeVarge, Barbara L.; Channick, Richard N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP LeVarge, BL (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM blevarge@partners.org FU Actelion; Bayer; Novartis; United Therapeutics FX R Channick has consulted for and/or received research grants from companies that produce treatments for pulmonary hypertension, including Actelion, Bayer, Novartis and United Therapeutics. 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 79 TC 2 Z9 2 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-6348 J9 EXPERT REV RESP MED JI Expert Rev. Respir. Med. PD JUN PY 2012 VL 6 IS 3 BP 255 EP 265 DI 10.1586/ERS.12.23 PG 11 WC Respiratory System SC Respiratory System GA 213LL UT WOS:000324058600010 PM 22788940 ER PT J AU Papakostas, GI AF Papakostas, G. I. TI TRD: Pharmacotherapeutic strategies for adults with major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Papakostas, G. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2012 VL 15 SU 1 MA S-02-001 BP 5 EP 5 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V34BS UT WOS:000209062500014 ER PT J AU Patel, SG Singh, B Stambuk, HE Carlson, D Bridger, PG Cantu, G Cheesman, AD Donald, P Fliss, D Gullane, P Kamata, S Janecka, I Kowalski, LP Kraus, DH Levine, PA Medina, LR Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP AF Patel, Snehal G. Singh, Bhuvanesh Stambuk, Hilda E. Carlson, Diane Bridger, Patrick G. Cantu, Giulio Cheesman, Anthony D. Donald, Paul Fliss, Dan Gullane, Patrick Kamata, Shin-etsu Janecka, Ivo Kowalski, Luiz P. Kraus, Dennis H. Levine, Paul A. Medina, Luiz R. Pradhan, Sultan Schramm, Victor Snyderman, Carl Wei, William I. Shah, Jatin P. TI Craniofacial Surgery for Esthesioneuroblastoma: Report of an International Collaborative Study SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE nose neoplasms/mortality/pathology/surgery/*therapy; esthesioneuroblastoma; olfactory/*therapy; combined modality therapy; radiotherapy; adjuvant; survival analysis ID SINONASAL UNDIFFERENTIATED CARCINOMA; OF-VIRGINIA EXPERIENCE; OLFACTORY NEUROBLASTOMA; NEUROENDOCRINE CARCINOMAS; SURGICAL-MANAGEMENT; RADIATION-THERAPY; SKULL BASE; TUMORS; RESECTION; PRESERVATION AB Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB. Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients. Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis. Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome. C1 [Patel, Snehal G.; Singh, Bhuvanesh; Kraus, Dennis H.; Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Stambuk, Hilda E.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Carlson, Diane] Cleveland Clin, Weston, FL USA. [Bridger, Patrick G.] Prince Wales Hosp, Sydney, NSW, Australia. [Cantu, Giulio] Inst Nazl, Milan, Italy. [Cheesman, Anthony D.] Royal Natl Throat Nose & Ear Hosp, London WC1X 8DA, England. [Donald, Paul] Univ Calif Davis, Davis, CA USA. [Fliss, Dan] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Otolaryngol, IL-69978 Tel Aviv, Israel. [Gullane, Patrick] Univ Toronto, Dept Otolaryngol Head & Neck Surg, Toronto, ON, Canada. [Kamata, Shin-etsu] Canc Inst Hosp, Tokyo, Japan. [Janecka, Ivo] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Kowalski, Luiz P.] Hosp Canc AC Camargo, Sao Paulo, Brazil. [Levine, Paul A.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Medina, Luiz R.] Hosp Clin Sao Paulo, Sao Paulo, Brazil. [Pradhan, Sultan] Tata Mem Hosp, Bombay 400012, Maharashtra, India. [Schramm, Victor] Ctr Head & Neck Surg, Denver, CO USA. [Snyderman, Carl] Univ Pittsburgh, Pittsburgh, PA USA. [Wei, William I.] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. RP Shah, JP (reprint author), Mem Sloan Kettering Canc Ctr, Head & Neck Serv, 1275 York Ave, New York, NY 10021 USA. EM shahj@mskcc.org RI Kowalski, Luiz/D-1701-2012; Francisco, Suely/D-9065-2014; OI Kowalski, Luiz/0000-0001-5865-9308; Kowalski, Luiz Paulo/0000-0002-0481-156X NR 46 TC 13 Z9 15 U1 1 U2 2 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 2012 VL 73 IS 3 BP 208 EP 220 DI 10.1055/s-0032-1311754 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 175YB UT WOS:000321268600009 PM 23730550 ER PT J AU Rapuano, BE Hackshaw, K MacDonald, DE AF Rapuano, Bruce E. Hackshaw, Kyle MacDonald, Daniel E. TI Heat or radiofrequency plasma glow discharge treatment of a titanium alloy stimulates osteoblast gene expression in the MC3T3 osteoprogenitor cell line SO JOURNAL OF PERIODONTAL AND IMPLANT SCIENCE LA English DT Article DE Cell differentiation; Dental implants; Fibronectins; Integrin alpha5beta1; Osteoblasts AB Purpose: The purpose of this study was to determine whether increasing the Ti6Al4V surface oxide negative charge through heat (600 degrees C) or radiofrequency plasma glow discharge (RFGD) pretreatment, with or without a subsequent coating with fibronectin, stimulated osteoblast gene marker expression in the MC3T3 osteoprogenitor cell line. Methods: Quantitative real-time polymerase chain reaction was used to measure changes over time in the mRNA levels for osteoblast gene markers, including alkaline phosphatase, bone sialoprotein, collagen type I (alpha 1), osteocalcin, osteopontin and parathyroid hormone-related peptide (PTH-rP), and the osteoblast precursor genes Runx2 and osterix. Results: Osteoprogenitors began to differentiate earlier on disks that were pretreated with heat or RFGD. The pretreatments increased gene marker expression in the absence of a fibronectin coating. However, pretreatments increased osteoblast gene expression for fibronectin-coated disks more than uncoated disks, suggesting a surface oxide-mediated specific enhancement of fibronectin's bioactivity. Heat pretreatment had greater effects on the mRNA expression of genes for PTH-rP, alkaline phosphatase and osteocalcin while RFGD pretreatment had greater effects on osteopontin and bone sialoprotein gene expression. Conclusions: The results suggest that heat and RFGD pretreatments of the Ti6Al4V surface oxide stimulated osteoblast differentiation through an enhancement of (a) coated fibronectin's bioactivity and (b) the bioactivities of other serum or matrix proteins. The quantitative differences in the effects of the two pretreatments on osteoblast gene marker expression may have arisen from the unique physico-chemical characteristics of each resultant oxide surface. Therefore, engineering the Ti6Al4V surface oxide to become more negatively charged can be used to accelerate osteoblast differentiation through fibronectin-dependent and independent mechanisms. C1 [Rapuano, Bruce E.; Hackshaw, Kyle; MacDonald, Daniel E.] Cornell Univ, Hosp Special Surg, Weill Med Coll, New York, NY 10021 USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. RP MacDonald, DE (reprint author), Columbia Univ, Langmuir Ctr Colloids & Interfaces, 911 SW Mudd Bldg,500 West 120th St, New York, NY 10027 USA. EM dem14@columbia.edu FU National Center for Research Resources, NIH [C06-RR12538-01]; [NIH RO1 DE017695] FX The project described was supported by Grant Number NIH RO1 DE017695 (Awarded to DEM). This material is also the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York. This investigation was also conducted at the HSS research facility constructed with support of Grant C06-RR12538-01 from the National Center for Research Resources, NIH. We would like to acknowledge Dr. Xiaoyu Hu for technical advice with the qRT-PCR analyses. Special thanks goes to Paul Lee, Carrie Guan, and Jani Jae Eun Lee for the preparation and treatment of titanium alloy disks. NR 38 TC 6 Z9 6 U1 3 U2 6 PU KOREAN ACAD PERIODONTOLOGY PI SEOUL PA OFFICIAL B-D 2212, 163 SINMUNRO 1-GA, JONGNO-GU, SEOUL, 110-990, SOUTH KOREA SN 2093-2278 EI 2093-2286 J9 J PERIODONTAL IMPLAN JI J. Periodontal Implant Sci. PD JUN PY 2012 VL 42 IS 3 BP 95 EP 104 DI 10.5051/jpis.2012.42.3.95 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V34HG UT WOS:000209076900006 PM 22803011 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI BLAZING A WAGON TRAIL TO OREGON: A Weekly Chronicle of the Great Migration of 1843 SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 EI 1930-0115 J9 J WEST JI J. West PD SUM PY 2012 VL 51 IS 3 BP 103 EP 104 PG 2 WC History SC History GA V31LQ UT WOS:000208885500022 ER PT J AU Imielinski, M Cha, SW Rejtar, T Richardson, EA Karger, BL Sgroi, DC AF Imielinski, Marcin Cha, Sangwon Rejtar, Tomas Richardson, Elizabeth A. Karger, Barry L. Sgroi, Dennis C. TI Integrated Proteomic, Transcriptomic, and Biological Network Analysis of Breast Carcinoma Reveals Molecular Features of Tumorigenesis and Clinical Relapse SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION SIGNATURES; SET ENRICHMENT ANALYSIS; HEAT-SHOCK PROTEINS; MASS-SPECTROMETRY; CANCER PROGRESSION; INDUCED APOPTOSIS; HISTOLOGIC GRADE; BONE METASTASIS; CELL-DEATH AB Gene and protein expression changes observed with tumorigenesis are often interpreted independently of each other and out of context of biological networks. To address these limitations, this study examined several approaches to integrate transcriptomic and proteomic data with known protein-protein and signaling interactions in estrogen receptor positive (ER+) breast cancer tumors. An approach that built networks from differentially expressed proteins and identified among them networks enriched in differentially expressed genes yielded the greatest success. This method identified a set of genes and proteins linking pathways of cellular stress response, cancer metabolism, and tumor microenvironment. The proposed network underscores several biologically intriguing events not previously studied in the context of ER+ breast cancer, including the overexpression of p38 mitogen-activated protein kinase and the overexpression of poly(ADP-ribose) polymerase 1. A gene-based expression signature biomarker built from this network was significantly predictive of clinical relapse in multiple independent cohorts of ER+ breast cancer patients, even after correcting for standard clinicopathological variables. The results of this study demonstrate the utility and power of an integrated quantitative proteomic, transcriptomic, and network analysis approach to discover robust and clinically meaningful molecular changes in tumors. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.014910, 1-15, 2012. C1 [Cha, Sangwon; Rejtar, Tomas; Karger, Barry L.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Imielinski, Marcin; Richardson, Elizabeth A.; Sgroi, Dennis C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Karger, BL (reprint author), Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. EM b.karger@neu.edu; dsgroi@partners.org FU National Institutes of Health [RO1GM15847, R01CA112021]; Susan G. Komen Breast Cancer Foundation; NCI SPORE in breast cancer at Massachusetts General Hospital; Avon Foundation FX This work was supported by National Institutes of Health Grants RO1GM15847 (to B. L. K.) and R01CA112021 (to D. C. S.) and funds from the Susan G. Komen Breast Cancer Foundation (to B. L. K. and D. C. S.), the NCI SPORE in breast cancer at Massachusetts General Hospital (to D. C. S.), and the Avon Foundation (to D. C. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 73 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUN PY 2012 VL 11 IS 6 AR M111.014910 DI 10.1074/mcp.M111.014910 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974CX UT WOS:000306408500014 PM 22240506 ER PT J AU Kuhn, E Whiteaker, JR Mani, DR Jackson, AM Zhao, L Pope, ME Smith, D Rivera, KD Anderson, NL Skates, SJ Pearson, TW Paulovich, AG Carr, SA AF Kuhn, Eric Whiteaker, Jeffrey R. Mani, D. R. Jackson, Angela M. Zhao, Lei Pope, Matthew E. Smith, Derek Rivera, Keith D. Anderson, N. Leigh Skates, Steven J. Pearson, Terry W. Paulovich, Amanda G. Carr, Steven A. TI Interlaboratory Evaluation of Automated, Multiplexed Peptide Immunoaffinity Enrichment Coupled to Multiple Reaction Monitoring Mass Spectrometry for Quantifying Proteins in Plasma SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID BIOMARKER DISCOVERY; QUANTIFICATION; ANTIBODIES; SERUM; PIPELINE; ASSAYS; IMMUNOASSAYS; QUANTITATION; VALIDATION; VERIFICATION AB The inability to quantify large numbers of proteins in tissues and biofluids with high precision, sensitivity, and throughput is a major bottleneck in biomarker studies. We previously demonstrated that coupling immunoaffinity enrichment using anti-peptide antibodies (SISCAPA) to multiple reaction monitoring mass spectrometry (MRM-MS) produces Immunoprecipitation MRM-MS (immuno-MRM-MS) assays that can be multiplexed to quantify proteins in plasma with high sensitivity, specificity, and precision. Here we report the first systematic evaluation of the interlaboratory performance of multiplexed (8-plex) immuno-MRM-MS in three independent labs. A staged study was carried out in which the effect of each processing and analysis step on assay coefficient of variance, limit of detection, limit of quantification, and recovery was evaluated. Limits of detection were at or below 1 ng/ml for the assayed proteins in 30 mu l of plasma. Assay reproducibility was acceptable for verification studies, with median intra-and interlaboratory coefficients of variance above the limit of quantification of 11% and <14%, respectively, for the entire immuno-MRM-MS assay process, including enzymatic digestion of plasma. Trypsin digestion and its requisite sample handling contributed the most to assay variability and reduced the recovery of target peptides from digested proteins. Using a stable isotope-labeled protein as an internal standard instead of stable isotope-labeled pep-tides to account for losses in the digestion process nearly doubled assay accuracy for this while improving assay precision 5%. Our results demonstrate that multiplexed immuno-MRM-MS can be made reproducible across independent laboratories and has the potential to be adopted widely for assaying proteins in matrices as complex as plasma. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.013854, 1-14, 2012. C1 [Kuhn, Eric; Mani, D. R.; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Whiteaker, Jeffrey R.; Zhao, Lei; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Jackson, Angela M.; Smith, Derek] Univ Victoria, Genome British Columbia Prote Core Facil, Victoria, BC, Canada. [Pearson, Terry W.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. [Rivera, Keith D.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC USA. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Carr, SA (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM scarr@Broad.MIT.edu FU National Institutes of Health [1U24 CA126476-02, 1U24CA160034]; NCI as part of the NCI Clinical Proteomic Technologies Initiative, National Institutes of Health [R01HL096738-02, HHSN268201000033C]; National Heart, Lung and Blood Institute; Genome Canada and Genome British Columbia; Entertainment Industry Foundation FX This work was supported by National Institutes of Health Grant 1U24 CA126476-02 and 1U24CA160034 (to S. A. C., N. L. A., and A. G. P.) from the NCI as part of the NCI Clinical Proteomic Technologies Initiative, National Institutes of Health Grant R01HL096738-02 and HHSN268201000033C (to S. A. C.) from the National Heart, Lung and Blood Institute, and a platform grant from Genome Canada and Genome British Columbia. This work was also supported in part by funds from the Women's Cancer Research Fund of the Entertainment Industry Foundation (to S. A. C. and A. G. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 40 TC 12 Z9 12 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUN PY 2012 VL 11 IS 6 AR M111.013854 DI 10.1074/mcp.M111.013854 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974CX UT WOS:000306408500037 PM 22199228 ER PT J AU Schlatzer, DM Dazard, JE Ewing, RM Ilchenko, S Tomcheko, SE Eid, S Ho, V Yanik, G Chance, MR Cooke, KR AF Schlatzer, Daniela M. Dazard, Jean-Eudes Ewing, Rob M. Ilchenko, Serguei Tomcheko, Sara E. Eid, Saada Ho, Vincent Yanik, Greg Chance, Mark R. Cooke, Kenneth R. TI Human Biomarker Discovery and Predictive Models for Disease Progression for Idiopathic Pneumonia Syndrome Following Allogeneic Stem Cell Transplantation SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID BONE-MARROW-TRANSPLANTATION; PEPTIDOGLYCAN RECOGNITION PROTEINS; GRAM-NEGATIVE BACTERIA; VERSUS-HOST-DISEASE; MASS-SPECTROMETRY; LUNG INJURY; PATHOGEN RECOGNITION; VARIABLE SELECTION; STATISTICAL-MODEL; INNATE IMMUNITY AB Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative therapy for many malignant and non-malignant conditions. Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication that limits successful outcomes. Preclinical models suggest that IPS represents an immune mediated attack on the lung involving elements of both the adaptive and the innate immune system. However, the etiology of IPS in humans is less well understood. To explore the disease pathway and uncover potential biomarkers of disease, we performed two separate label-free, proteomics experiments defining the plasma protein profiles of allogeneic SCT patients with IPS. Samples obtained from SCT recipients without complications served as controls. The initial discovery study, intended to explore the disease pathway in humans, identified a set of 81 IPS-associated proteins. These data revealed similarities between the known IPS pathways in mice and the condition in humans, in particular in the acute phase response. In addition, pattern recognition pathways were judged to be significant as a function of development of IPS, and from this pathway we chose the lipopolysaccaharide-binding protein (LBP) protein as a candidate molecular diagnostic for IPS, and verified its increase as a function of disease using an ELISA assay. In a separately designed study, we identified protein-based classifiers that could predict, at day 0 of SCT, patients who: 1) progress to IPS and 2) respond to cytokine neutralization therapy. Using cross-validation strategies, we built highly predictive classifier models of both disease progression and therapeutic response. In sum, data generated in this report confirm previous clinical and experimental findings, provide new insights into the pathophysiology of IPS, identify potential molecular classifiers of the condition, and uncover a set of markers potentially of interest for patient stratification as a basis for individualized therapy. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.015479, 1-15, 2012. C1 [Schlatzer, Daniela M.; Dazard, Jean-Eudes; Ewing, Rob M.; Ilchenko, Serguei; Tomcheko, Sara E.; Chance, Mark R.] Case Western Reserve Univ, Sch Med, Ctr Prote & Bioinformat, Cleveland, OH 44106 USA. [Ewing, Rob M.; Chance, Mark R.] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. [Eid, Saada; Cooke, Kenneth R.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. [Ho, Vincent] Univ Michigan, Dept Pediat, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA. [Yanik, Greg] Dana Farber Canc Inst, Dept Med Oncol, Blood & Marrow Transplantat Program, Boston, MA 02115 USA. RP Chance, MR (reprint author), Case Western Reserve Univ, Sch Med, Ctr Prote & Bioinformat, 10900 Euclid Ave,BRB 930, Cleveland, OH 44106 USA. EM mark.chance@case.edu OI Dazard, Jean-Eudes/0000-0003-4720-3684; Ewing, Rob/0000-0001-6510-4001 FU Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Case Western Reserve University/Cleveland Clinic CTSA from the National Center for Research Resources (NCRR), National Institutes of Health and NIH Roadmap for Medical Research [UL1 R024989]; Case Comprehensive Cancer Center [P30-CA04370] FX This work was supported by Burroughs Wellcome Fund, The Leukemia and Lymphoma Society, and the Case Western Reserve University/Cleveland Clinic CTSA (Grant Number UL1 R024989) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health and NIH Roadmap for Medical Research. We also acknowledge support from the Case Comprehensive Cancer Center Core Grant (P30-CA04370). NR 73 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUN PY 2012 VL 11 IS 6 AR M111.015479 DI 10.1074/mcp.M111.015479 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974CX UT WOS:000306408500033 PM 22337588 ER PT J AU Zhong, J Kim, MS Chaerkady, R Wu, XY Huang, TC Getnet, D Mitchell, CJ Palapetta, SM Sharma, J O'Meally, RN Cole, RN Yoda, A Moritz, A Loriaux, MM Rush, J Weinstock, DM Tyner, JW Pandey, A AF Zhong, Jun Kim, Min-Sik Chaerkady, Raghothama Wu, Xinyan Huang, Tai-Chung Getnet, Derese Mitchell, Christopher J. Palapetta, Shyam M. Sharma, Jyoti O'Meally, Robert N. Cole, Robert N. Yoda, Akinori Moritz, Albrecht Loriaux, Marc M. Rush, John Weinstock, David M. Tyner, Jeffrey W. Pandey, Akhilesh TI TSLP Signaling Network Revealed by SILAC-Based Phosphoproteomics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID THYMIC STROMAL LYMPHOPOIETIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROTEIN-TYROSINE-PHOSPHATASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; STEM-CELL DIFFERENTIATION; BTK INHIBITOR PCI-32765; HUMAN EPITHELIAL-CELLS; ABL-POSITIVE CELLS; N-TERMINAL KINASE; IGM(+) B-CELLS AB Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. TSLP requires a heterodimeric receptor complex consisting of IL-7 receptor alpha subunit and its unique TSLP receptor (gene symbol CRLF2) to transmit signals in cells. Abnormal TSLP signaling (e. g. overexpression of TSLP or its unique receptor TSLPR) contributes to the development of a number of diseases including asthma and leukemia. However, a detailed understanding of the signaling pathways activated by TSLP remains elusive. In this study, we performed a global quantitative phosphoproteomic analysis of the TSLP signaling network using stable isotope labeling by amino acids in cell culture. By employing titanium dioxide in addition to antiphosphotyrosine antibodies as enrichment methods, we identified 4164 phosphopeptides on 1670 phosphoproteins. Using stable isotope labeling by amino acids in cell culture-based quantitation, we determined that the phosphorylation status of 226 proteins was modulated by TSLP stimulation. Our analysis identified activation of several members of the Src and Tec families of kinases including Btk, Lyn, and Tec by TSLP for the first time. In addition, we report TSLP-induced phosphorylation of protein phosphatases such as Ptpn6 (SHP-1) and Ptpn11 (Shp2), which has also not been reported previously. Co-immunoprecipitation assays showed that Shp2 binds to the adapter protein Gab2 in a TSLP-dependent manner. This is the first demonstration of an inducible protein complex in TSLP signaling. A kinase inhibitor screen revealed that pharmacological inhibition of PI-3 kinase, Jak family kinases, Src family kinases or Btk suppressed TSLP-dependent cellular proliferation making them candidate therapeutic targets in diseases resulting from aberrant TSLP signaling. Our study is the first phosphoproteomic analysis of the TSLP signaling pathway that greatly expands our understanding of TSLP signaling and provides novel therapeutic targets for TSLP/TSLPR-associated diseases in humans. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.017764, 1-22, 2012. C1 [Zhong, Jun; Kim, Min-Sik; Chaerkady, Raghothama; Wu, Xinyan; Huang, Tai-Chung; Getnet, Derese; Mitchell, Christopher J.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Zhong, Jun; Kim, Min-Sik; Chaerkady, Raghothama; Wu, Xinyan; Huang, Tai-Chung; Getnet, Derese; Mitchell, Christopher J.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [Zhong, Jun; Kim, Min-Sik; Chaerkady, Raghothama; Wu, Xinyan; Huang, Tai-Chung; Getnet, Derese; Mitchell, Christopher J.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Zhong, Jun; Kim, Min-Sik; Chaerkady, Raghothama; Wu, Xinyan; Huang, Tai-Chung; Getnet, Derese; Mitchell, Christopher J.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [O'Meally, Robert N.; Cole, Robert N.] Johns Hopkins Univ, Sch Med, Inst Basic Biomed Sci, Mass Spectrometry & Prote Facil, Baltimore, MD 21205 USA. [Mitchell, Christopher J.] Johns Hopkins Univ, Sch Med, Grad Program Biochem Cellular & Mol Biol, Baltimore, MD 21205 USA. [Chaerkady, Raghothama; Palapetta, Shyam M.; Sharma, Jyoti] Inst Bioinformat, Bangalore 560066, Karnataka, India. [Palapetta, Shyam M.] Pondicherry Univ, Sch Life Sci, Ctr Excellence Bioinformat, Pondicherry 605014, India. [Sharma, Jyoti] Manipal Univ, Manipal 576104, Karnataka, India. [Yoda, Akinori; Weinstock, David M.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Moritz, Albrecht; Rush, John] Cell Signaling Technol Inc, Danvers, MA 01923 USA. [Loriaux, Marc M.] Oregon Hlth & Sci Univ, Dept Anat Pathol, Knight Canc Inst, Portland, OR 97239 USA. [Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Knight Canc Inst, Portland, OR 97239 USA. RP Pandey, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, 733 N Broadway,BRB Room 527, Baltimore, MD 21205 USA. EM pandey@jhmi.edu RI Zhong, Jun/D-1662-2010; Pandey, Akhilesh/B-4127-2009; Kim, Min-Sik/M-3488-2016; OI Zhong, Jun/0000-0003-3148-4143; Pandey, Akhilesh/0000-0001-9943-6127; Kim, Min-Sik/0000-0001-7317-5360; Huang, Tai-Chung/0000-0002-1625-7295; Tyner, Jeffrey/0000-0002-2133-0960; Palapetta, Shyam Mohan/0000-0002-7674-1310 FU Department of Biotechnology, Government of India; Council of Scientific and Industrial Research (CSIR), Government of India; National Heart Lung and Blood Institute [HHSN268201000032C]; National Institutes of Health (NIH) [S10RR023025]; NIH Roadmap grant "Technology Center for Networks and Pathways" [U54 RR 020839] FX We thank the Department of Biotechnology, Government of India for research support to the Institute of Bioinformatics. Shyam M. Palapetta and Jyoti Sharma are recipients of a Senior Research Fellowship from the Council of Scientific and Industrial Research (CSIR), Government of India. We thank Bernard Delanghe (Thermo Fisher Scientific (Bremen) GmbH, Bremen, Germany) for providing access to the Proteome Discoverer platform.; The work was supported by a contract HHSN268201000032C from the National Heart Lung and Blood Institute (R. N. C. and A. P.) and by a grant S10RR023025 from the High End Instrumentation Program of the National Institutes of Health (NIH) (A. P.) and an NIH Roadmap grant "Technology Center for Networks and Pathways" U54 RR 020839 (A. P.). NR 142 TC 0 Z9 2 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUN PY 2012 VL 11 IS 6 AR M112.017764 DI 10.1074/mcp.M112.017764 PG 22 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 974CX UT WOS:000306408500034 PM 22345495 ER PT J AU Oppenheim, CE AF Oppenheim, Claire E. TI Nelson Mandela and the Power of Ubuntu SO RELIGIONS LA English DT Article DE Ubuntu; botho; unity; community; Afro-communitarianism; humanity; apartheid AB Nelson Mandela dedicated his life to fighting for the freedom of his South African kin of all colors against the institution of apartheid. He spent twenty-seven years fighting from within prison, only gaining his freedom when his fellow South Africans could claim it as well. This article demonstrates how his faith, his spiritual development and his noble purpose can be conceptualized through the lens of Ubuntu: the African ethic of community, unity, humanity and harmony. C1 Massachusetts Gen Hosp, Erich Lindemann Mental Hlth Ctr, Boston, MA 02114 USA. RP Oppenheim, CE (reprint author), Massachusetts Gen Hosp, Erich Lindemann Mental Hlth Ctr, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM claireoppenheim@gmail.com NR 4 TC 4 Z9 5 U1 0 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2077-1444 J9 RELIGIONS JI Religions PD JUN PY 2012 VL 3 IS 2 BP 369 EP 388 DI 10.3390/rel3020369 PG 20 WC Religion SC Religion GA 175SR UT WOS:000321253800014 ER PT J AU Guanci, MM AF Guanci, Mary McKenna TI Our hospital is new at using hypothermia following cardiac arrest and it usually does not get started until the patient reaches the cardiac intensive care unit. The doctors want to complete the cardiac catheterization procedure first. Are there any suggestions for getting hypothermia started sooner? SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Letter C1 Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA. RP Guanci, MM (reprint author), Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD JUN 1 PY 2012 VL 2 IS 2 BP 99 EP 99 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V38PK UT WOS:000209355100012 ER PT J AU Nakhlis, F Golshan, M AF Nakhlis, Faina Golshan, Mehra TI Bevacizumab: where do we go from here in breast cancer? SO TRANSLATIONAL CANCER RESEARCH LA English DT Article C1 Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Faulkner Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 2 TC 4 Z9 6 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD JUN PY 2012 VL 1 IS 1 BP 55 EP 56 DI 10.3978/j.issn.2218-676X.2012.03.01 PG 2 WC Oncology SC Oncology GA V42VY UT WOS:000209642500009 ER PT J AU Yang, YR Song, M Lee, H Jeon, Y Choi, EJ Jang, HJ Moon, HY Byun, HY Kim, EK Kim, DH Lee, MN Koh, A Ghim, J Choi, JH Lee-Kwon, W Kim, KT Ryu, SH Suh, PG AF Yang, Yong Ryoul Song, Minseok Lee, Ho Jeon, Yoon Choi, Eun-Jeong Jang, Hyun-Jun Moon, Hyo Youl Byun, Ha-Young Kim, Eung-Kyun Kim, Dae Hyun Lee, Mi Nam Koh, Ara Ghim, Jaewang Choi, Jang Hyun Lee-Kwon, Whaseon Kim, Kyong Tai Ryu, Sung Ho Suh, Pann-Ghill TI O-GlcNAcase is essential for embryonic development and maintenance of genomic stability SO AGING CELL LA English DT Article DE aging; genomic instability; O-GlcNAcase; O-GlcNAcylation; O-GlcNAc transferase ID BETA-N-ACETYLGLUCOSAMINE; RNA-POLYMERASE-II; DEPENDENT PHOSPHORYLATION; MITOTIC PROGRESSION; TERMINAL DOMAIN; XENOPUS-LAEVIS; SPINDLE POLES; X-CHROMOSOME; PROTEIN; TRANSFERASE AB Dysregulation of O-GlcNAc modification catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) contributes to the etiology of chronic diseases of aging, including cancer, cardiovascular disease, type 2 diabetes, and Alzheimers disease. Here we found that natural aging in wild-type mice was marked by a decrease in OGA and OGT protein levels and an increase in O-GlcNAcylation in various tissues. Genetic disruption of OGA resulted in constitutively elevated O-GlcNAcylation in embryos and led to neonatal lethality with developmental delay. Importantly, we observed that serum-stimulated cell cycle entry induced increased O-GlcNAcylation and decreased its level after release from G2/M arrest, indicating that O-GlcNAc cycling by OGT and OGA is required for precise cell cycle control. Constitutively, elevated O-GlcNAcylation by OGA disruption impaired cell proliferation and resulted in mitotic defects with downregulation of mitotic regulators. OGA loss led to mitotic defects including cytokinesis failure and binucleation, increased lagging chromosomes, and micronuclei formation. These findings suggest an important role for O-GlcNAc cycling by OGA in embryonic development and the regulation of the maintenance of genomic stability linked to the aging process. C1 [Yang, Yong Ryoul; Choi, Eun-Jeong; Jang, Hyun-Jun; Byun, Ha-Young; Kim, Eung-Kyun; Lee, Mi Nam; Koh, Ara; Ghim, Jaewang; Kim, Kyong Tai; Ryu, Sung Ho; Suh, Pann-Ghill] Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang 790784, Kyungbuk, South Korea. [Yang, Yong Ryoul; Jang, Hyun-Jun; Moon, Hyo Youl; Byun, Ha-Young; Kim, Eung-Kyun; Kim, Dae Hyun; Lee-Kwon, Whaseon; Suh, Pann-Ghill] Ulsan Natl Inst Sci & Technol, Sch Nanobiotechnol & Chem Engn, Ulsan 689798, South Korea. [Song, Minseok] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA. [Lee, Ho; Jeon, Yoon] Natl Canc Ctr, Canc Expt Resources Branch, Goyang Si 410769, Gyeonggi Do, South Korea. [Moon, Hyo Youl] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, South Korea. [Choi, Jang Hyun] Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA. [Choi, Jang Hyun] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Suh, PG (reprint author), Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang 790784, Kyungbuk, South Korea. EM pgsuh@unist.ac.kr RI Choi, Jang Hyun/B-3055-2012 FU National Research Foundation of Korea [PGB013]; Korean Government [KRF-2007-341-C00027, 2010-0029434]; Korean Ministry of Education, Science and Technology (Anti-aging and Well-being Research Center) FX This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (KRF-2007-341-C00027), a grant from the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Anti-aging and Well-being Research Center), the National Research Foundation of Korea Grant funded by the Korean government (no. 2010-0029434), and the Fusion Pioneer Project (PGB013) from the National Research Foundation of Korea. NR 43 TC 59 Z9 60 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD JUN PY 2012 VL 11 IS 3 BP 439 EP 448 DI 10.1111/j.1474-9726.2012.00801.x PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 940RG UT WOS:000303910100009 PM 22314054 ER PT J AU Allen, NE Javdani, S Lehrner, AL Walden, AL AF Allen, Nicole E. Javdani, Shabnam Lehrner, Amy L. Walden, Angela L. TI "Changing the Text": Modeling Council Capacity to Produce Institutionalized Change SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE Councils; Institutionalized change; Coordinating councils; Coalitions; Domestic violence; Intimate partner violence; Interagency coordination ID VIOLENCE COORDINATING COUNCILS; COMMUNITY-HEALTH COALITIONS; SUBSTANCE-ABUSE PREVENTION; GOVERNANCE PROCESSES; PARTICIPATION; EMPOWERMENT; PARTNERSHIPS; OUTCOMES; IMPLEMENTATION; PERSPECTIVE AB Collaboration is a ubiquitous approach to change, but is notoriously difficult and not definitively linked to desirable outcomes. Not surprisingly, the collaboration literature is replete with numerous facilitators and barriers to collaborative efforts. The current study aimed to develop a parsimonious model of factors influencing the success of collaborative efforts both internal and external to the council, including, (a) features of the council environment, (b) intermediate outcomes including the empowerment of members in the council context and the degree to which councils have generated social capital and (c) the extent to which collaborative efforts are occurring in a community context supportive of their aims. In particular, this study examines whether these factors affect the extent to which councils are positioned to achieve institutionalized change, or changes "in the text" that govern front line providers' (e.g., police, advocates) practices in the community response to intimate partner violence. Results suggest that perceived member empowerment, generation of social capital, and supportive community context are the most important predictors of the extent to which councils foster shifts in institutionalized change. Features of the council environment are only indirectly related to the degree to which institutionalized change is ultimately fostered as mediated by the generation of social capital. This suggests that the ability of members to act as change agents and the extent to which those in power support council efforts figure more prominently to facilitate or constrain council efforts than council functioning itself. C1 [Allen, Nicole E.; Javdani, Shabnam; Walden, Angela L.] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Lehrner, Amy L.] James J Peters VA Med Ctr, Traumat Stress Studies Div, Bronx, NY USA. RP Allen, NE (reprint author), Univ Illinois, Dept Psychol, 603 E Daniel St, Champaign, IL 61820 USA. EM allenne@illinois.edu OI Javdani, Shabnam/0000-0003-3949-1970 NR 50 TC 13 Z9 13 U1 2 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD JUN PY 2012 VL 49 IS 3-4 BP 317 EP 331 DI 10.1007/s10464-011-9460-z PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 939HR UT WOS:000303800600002 PM 21842302 ER PT J AU Cashman, EC Smyth, D AF Cashman, Emma Catherine Smyth, David TI Primary headache syndromes and sinus headache: An approach to diagnosis and management SO AURIS NASUS LARYNX LA English DT Review DE Headache; Migraine; Sinus; FESS ID TRIGEMINAL-AUTONOMIC CEPHALALGIAS; TENSION-TYPE HEADACHE; CLUSTER HEADACHE; MIGRAINE; PREVALENCE AB Chronic rhinosinusitis (CRS) and primary headache syndromes are common disease entities and headache and facial pain are common reasons for referral to otolaryngology units. Because of an association of nasal symptoms with primary headache syndromes and considerable similarities in their clinical presentations, primary headache syndromes may be misdiagnosed as sinus disease and vice versa. In this review we examine the evidence on which otolaryngologists can base clinical diagnosis and management and offer an approach to distinguishing these common clinical entities. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Cashman, Emma Catherine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Smyth, David] Waterford Reg Hosp, Dept Otolaryngol, Waterford, Ireland. RP Cashman, EC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Longwood Ave, Boston, MA 02115 USA. EM emma_cashman@dfci.harvard.ie NR 28 TC 3 Z9 4 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0385-8146 J9 AURIS NASUS LARYNX JI Auris Nasus Larynx PD JUN PY 2012 VL 39 IS 3 BP 257 EP 260 DI 10.1016/j.anl.2011.05.003 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 937WT UT WOS:000303695200001 PM 21862253 ER PT J AU Gunduz-Bruce, H Reinhart, RMG Roach, BJ Gueorguieva, R Oliver, S D'Souza, DC Ford, JM Krystal, JH Mathalon, DH AF Gunduz-Bruce, Handan Reinhart, Robert M. G. Roach, Brian J. Gueorguieva, Ralitza Oliver, Stephen D'Souza, Deepak C. Ford, Judith M. Krystal, John H. Mathalon, Daniel H. TI Glutamatergic Modulation of Auditory Information Processing in the Human Brain SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Glutamate; ketamine; MMN; N-acetylcysteine; NMDA; P300 ID MISMATCH NEGATIVITY MMN; HUMAN SELECTIVE ATTENTION; N-ACETYL-CYSTEINE; HEALTHY-VOLUNTEERS; P300 AMPLITUDE; GLUTATHIONE PRECURSOR; MENSTRUAL-CYCLE; SYSTEM X(C)(-); IN-VIVO; SCHIZOPHRENIA AB Background: Auditory mismatch negativity (MMN) and P300 event-related potentials (ERPs) are reduced in schizophrenia patients and healthy volunteers administered the N-methyl-D-aspartate glutamate receptor antagonist, ketamine. In rodents, N-acetylcysteine (NAC), a stimulator of the cystine-glutamate exchanger, attenuates the cognitive and behavioral effects of N-methyl-D-aspartate receptor antagonists. On the basis of these findings, we tested whether NAC would reduce ketamine effects on behavior, MMN, and P300 in healthy humans. Methods: This randomized, double-blind, placebo-controlled study consisted of 2 test days during which subjects (n = 16) were administered oral NAC (3000 mg in divided doses) or matching placebo 165 min before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Behavioral and ERP data including auditory MMN and P300 were collected during each test day. Results: Ketamine produced psychotic-like positive symptoms, reductions in working memory and sustained attention performance, and amplitude reductions for the frequency- and intensity-deviant MMNs and P300. NAC pretreatment did not reduce the behavioral or ERP effects of ketamine. In addition, NAC reduced frequency-deviant MMN amplitude and increased target and novelty P3 amplitudes. The decrements in frequency-deviant MMN amplitude produced by ketamine and NAC were not additive. Conclusions: NAC did not attenuate the effects of ketamine in humans, in contrast to previous studies in animals. NAC merits further investigation as a cognitive enhancing agent due to its ability to increase the P300 amplitude. C1 [Gunduz-Bruce, Handan; D'Souza, Deepak C.; Krystal, John H.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Gunduz-Bruce, Handan; Gueorguieva, Ralitza; Oliver, Stephen; D'Souza, Deepak C.; Ford, Judith M.; Krystal, John H.; Mathalon, Daniel H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Reinhart, Robert M. G.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ford, Judith M.; Mathalon, Daniel H.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Gunduz-Bruce, H (reprint author), VA Connecticut Healthcare Syst, 116-A,950 Campbell Ave, West Haven, CT 06516 USA. EM handan.gunduz-bruce@yale.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974; Gueorguieva, Ralitza/0000-0003-0944-5973 FU National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD); National Institute on Alcohol Abuse and Alcoholism [K05 AA 14906, 2P50 AA 012870]; US Department of Veterans Affairs Alcohol Research Center, National Center Post Traumatic Stress Disorder, Clinical Neurosciences Division, West Haven, Connecticut; VA Schizophrenia Biological Research Center; National Institute of Mental Health [MH40052, MH 58262, MH067967]; Astra Zeneca; Abbott Laboratories; Eli Lilly; Organon; Pfizer; Sanofi; Department of Veterans Affairs; Janssen Research Foundation; [R01 MH076989] FX This study was supported by a National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) Hammerschlag Young Investigator Award to Dr. Gunduz-Bruce. Part of the data was previously presented as a poster at the 2007 annual meeting of the American College of Neuropsychopharmacology. We are thankful to the Biostudies Laboratory Nursing Staff; Angelina M. Genovese, RNC, MBA; Elizabeth O'Donnell, RN; Michelle Sanpedro, RN; and Brenda Breault, RN, BSN, for their outstanding nursing; and Sonah Perry, R.Ph., for excellent Research Pharmacy support. We also thank all the research participants. This study was also partly supported by funding from the National Institute on Alcohol Abuse and Alcoholism, K05 AA 14906, National Institute on Alcohol Abuse and Alcoholism, 2P50 AA 012870, US Department of Veterans Affairs Alcohol Research Center, National Center Post Traumatic Stress Disorder, Clinical Neurosciences Division, West Haven, Connecticut, to JHK; R01 MH076989 to DHM; VA Schizophrenia Biological Research Center, and grants from the National Institute of Mental Health (MH40052, MH 58262, MH067967) and NARSAD to JMF.; Drs. Gunduz-Bruce, Gueorguieva, Ford, and Mathalon and Mr. Reinhart, Mr. Roach, and Mr. Oliver report no biomedical financial interests or potential conflict of interests. Dr. D'Souza reports research grant support from Astra Zeneca, Abbott Laboratories, Eli Lilly, Organon, Pfizer, and Sanofi. Dr. Krystal reports serving as consultant for the following companies (the Individual Consultant Agreements listed are <$10,000/year): Aisling Capital, LLC, AstraZeneca Pharmaceuticals, Brintnall and Nicolini, Easton Associates, Gilead Sciences, GlaxoSmith-Kline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Merz Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche, SK Holdings, Takeda Industries, and Teva Pharmaceutical Industries. Dr. Krystal also serves for the Scientific Advisory Board of Abbott Laboratories, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest Laboratories, Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Naurex, Pfizer Pharmaceuticals, and Shire Pharmaceuticals. Dr. Krystal holds Exercisable Warrant Options that include Tetragenex Pharmaceuticals (value <$150), and he serves as Board of Directors for the Coalition for Translational Research in Alcohol and Substance Use Disorders. Dr. Krystal is a President Elect for American College of Neuropsychopharmacology and receives research support from Department of Veterans Affairs and Janssen Research Foundation (provided drug and some study support to the Department of Veterans Affairs). Dr. Krystal receives >$10,000 as the Editor of Biological Psychiatry. Patents and Inventions for Dr. Krystal include: 1) Seibyl JP, Krystal JH, Charney DS. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent #:5,447,948. September 5, 1995; 2) co-inventor with Dr. Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1); and 3) Intranasal Administration of Ketamine to Treat Depression (pending). NR 75 TC 28 Z9 29 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2012 VL 71 IS 11 BP 969 EP 977 DI 10.1016/j.biopsych.2011.09.031 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 939MH UT WOS:000303814800009 PM 22036036 ER PT J AU Yomogida, K Chou, Y Pang, J Baravati, B Maniaci, BJ Wu, S Zhu, Y Chu, CQ AF Yomogida, Kentaro Chou, Yuan Pang, Jonathan Baravati, Bobby Maniaci, Brian J. Wu, Shili Zhu, Yong Chu, Cong-Qiu TI Streptavidin suppresses T cell activation and inhibits IL-2 production and CD25 expression SO CYTOKINE LA English DT Article DE Streptavidin; Biotin; T Cell activation; Interleukin 2; Interleukin 2 receptor ID JURKAT CELLS; PRETARGETED RADIOIMMUNOTHERAPY; RENAL-TRANSPLANTATION; CHAIN IMMUNOTOXIN; BIOTIN DEFICIENCY; BINDING-PROTEIN; FUSION PROTEIN; REJECTION; DIFFERENTIATION; BIOTINYLATION AB Streptavidin is widely used as a detection tool in biology research because of its high affinity and specificity binding to biotin. Biotin-streptavidin system has also been explored for detection of infection and tumor in clinical medicine. Here, we show immunosuppressive property of streptavidin on T cell activation and proliferation. Upon CD3 and CD28 stimulation, CD4(+) T cells produce interleukin 2 (IL-2) and express IL-2 receptor alpha chain (CD25). Addition of streptavidin in T cell culture suppressed IL-2 synthesis and CD25 expression with no cytotoxicity. The immunosuppressive effect of streptavidin was reversed by excessive biotin. Conjugated to a single chain anti-CD7 variable fragment (scFvCD7), streptavidin was directly delivered to T cells and showed substantially more profound suppressive effect on T cell activation. These results suggest that streptavidin could potentially be used as a novel immunomodulator. Published by Elsevier Ltd. C1 [Yomogida, Kentaro; Chou, Yuan; Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, Portland, OR USA. [Yomogida, Kentaro; Chou, Yuan; Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. [Pang, Jonathan; Baravati, Bobby; Maniaci, Brian J.; Wu, Shili; Zhu, Yong] VivoScript Inc, Costa Mesa, CA USA. RP Chu, CQ (reprint author), 3181 SW Sam Jackson Pk Rd 0P09, Portland, OR 97239 USA. EM chuc@ohsu.edu FU NIH [AR055254]; Portland VA Medical Center FX This work was supported by a Grant from NIH to C.Q.C. (AR055254) and Portland VA Medical Center. NR 46 TC 4 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 2012 VL 58 IS 3 BP 431 EP 436 DI 10.1016/j.cyto.2012.02.007 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 941FA UT WOS:000303947900018 PM 22410319 ER PT J AU Walker, DD Reeves, TD de Costa, AM Schuyler, C Young, MRI AF Walker, David D. Reeves, Travis D. de Costa, Anna-Maria Schuyler, Corinne Young, M. Rita I. TI Immunological modulation by 1 alpha,25-dihydroxyvitamin D-3 in patients with squamous cell carcinoma of the head and neck SO CYTOKINE LA English DT Article DE Cytokines; Head and neck cancer; HNSCC; Vitamin D ID ENDOTHELIAL GROWTH-FACTOR; CANCER-PATIENTS; PERIPHERAL-BLOOD; CD34(+) CELLS; DENDRITIC CELLS; VITAMIN-D; IMMUNITY; DIFFERENTIATION; CARCINOGENESIS; IMMUNOTHERAPY AB Prior studies showing that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] stimulated intratumoral immune infiltration were extended to analysis of cytokine profiles in the periphery and in oral tissues. Most prominent was the disparity between cytokine levels in plasma and in either pathologically normal oral tissue or HNSCC tissue from patients that were untreated or treated with 1,25(OH)(2)D-3. Levels of IL-6 and IL-10, but not IL-2, IFN-gamma or TNF-alpha, tended to be increased in the plasma of HNSCC patients and 1,25(OH)(2)D-3 further increased plasma levels of all of these cytokines. While these cytokines tended to be increased in HNSCC tissue, 1,25(OH)(2)D-3 resulted in variable cytokine responses that showed a general tendency toward further increased levels. Levels of IL-8 and VEGF were increased in plasma and tissue of untreated HNSCC patients, and were further increased in plasma, but not in tissues, of patients treated with 1,25(OH)(2)D-3. Levels of IL-1 alpha and IL-1 beta were similar in plasma of controls and HNSCC patients, but were increased in HNSCC tissues. In contrast to that seen in plasma where 1,25(OH)(2)D-3 increased levels of IL-1 alpha and IL-1 beta, this was not seen in tissue following 1,25(OH)(2)D-3 treatment. These results show a discordant relationship between systemic and intratumoral cytokine profiles and suggest a tendency of 1,25(OH)(2)D(3)to increase a multitude of cytokines within tumor tissue. Published by Elsevier Ltd. C1 [Walker, David D.; Reeves, Travis D.; Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [de Costa, Anna-Maria] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv, 109 Bee St, Charleston, SC 29401 USA. EM david.walker4@gmail.com; reevestd@musc.edu; clarkann@musc.edu; schuylec@musc.edu; rita.young@va.gov FU Biomedical Laboratory and Clinical Sciences of the Department of Veterans Affairs; National Institute of Health [I01-CX000100, R01-CA128837, R01-DE018268] FX This work has been supported by awards from the Biomedical Laboratory and Clinical Sciences Programs of the Department of Veterans Affairs and by grants from the National Institute of Health (MRIY, I01-CX000100, R01-CA128837 and R01-DE018268). NR 28 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 2012 VL 58 IS 3 BP 448 EP 454 DI 10.1016/j.cyto.2012.03.002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 941FA UT WOS:000303947900020 PM 22450225 ER PT J AU Zhang, HJ Kim, A Abraham, N Khan, LA Hall, DH Fleming, JT Gobel, V AF Zhang, Hongjie Kim, Ahlee Abraham, Nessy Khan, Liakot A. Hall, David H. Fleming, John T. Gobel, Verena TI Clathrin and AP-1 regulate apical polarity and lumen formation during C. elegans tubulogenesis SO DEVELOPMENT LA English DT Article DE Caenorhabditis elegans; Polarity; Tubulogenesis; Clathrin; AP-1; Sphingolipids ID EPITHELIAL-CELL POLARITY; NEMATODE CAENORHABDITIS-ELEGANS; MICROVILLUS INCLUSION DISEASE; RECEPTOR-MEDIATED ENDOCYTOSIS; MOLECULAR-MECHANISM; COMPLEX; GENE; MORPHOGENESIS; MICROSCOPY; PHOSPHOINOSITIDES AB Clathrin coats vesicles in all eukaryotic cells and has a well-defined role in endocytosis, moving molecules away from the plasma membrane. Its function on routes towards the plasma membrane was only recently appreciated and is thought to be limited to basolateral transport. Here, an unbiased RNAi-based tubulogenesis screen identifies a role of clathrin (CHC-1) and its AP-1 adaptor in apical polarity during de novo lumenal membrane biogenesis in the C. elegans intestine. We show that CHC-1/AP-1-mediated polarized transport intersects with a sphingolipid-dependent apical sorting process. Depleting each presumed trafficking component mislocalizes the same set of apical membrane molecules basolaterally, including the polarity regulator PAR-6, and generates ectopic lateral lumens. GFP::CHC-1 and BODIPY-ceramide vesicles associate perinuclearly and assemble asymmetrically at polarized plasma membrane domains in a co-dependent and AP-1-dependent manner. Based on these findings, we propose a trafficking pathway for apical membrane polarity and lumen morphogenesis that implies: (1) a clathrin/AP-1 function on an apically directed transport route; and (2) the convergence of this route with a sphingolipid-dependent apical trafficking path. C1 [Zhang, Hongjie; Kim, Ahlee; Abraham, Nessy; Khan, Liakot A.; Fleming, John T.; Gobel, Verena] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Zhang, Hongjie; Kim, Ahlee; Abraham, Nessy; Khan, Liakot A.; Fleming, John T.; Gobel, Verena] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hall, David H.] Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Ctr C Elegans Anat, Bronx, NY 10461 USA. RP Gobel, V (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM gobel@helix.mgh.harvard.edu FU National Institutes of Health [HD044589, GM078653]; Mattina R. Proctor Award FX This work was supported by the National Institutes of Health [grants HD044589 and GM078653] and a Mattina R. Proctor Award to V.G. Deposited in PMC for release after 12 months. NR 55 TC 20 Z9 23 U1 0 U2 5 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 2012 VL 139 IS 11 BP 2071 EP 2083 DI 10.1242/dev.077347 PG 13 WC Developmental Biology SC Developmental Biology GA 940SV UT WOS:000303914300023 PM 22535410 ER PT J AU Cortelli, JR Fernandes, CB Costa, FO Cortelli, SC Kajiya, M Howell, SC Kawai, T AF Cortelli, J. R. Fernandes, C. B. Costa, F. O. Cortelli, S. C. Kajiya, M. Howell, S. C. Kawai, T. TI Detection of periodontal pathogens in newborns and children with mixed dentition SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; SUBGINGIVAL PLAQUE; HEALTHY-CHILDREN; YOUNG-CHILDREN; MICROBIOTA; BACTERIA; COLONIZATION; GINGIVITIS; PREVALENCE; SAMPLES AB We report the age-related prevalence of red complex periodontal pathogens, , , and , along with four strains of orange complex pathogens. The bacteria present in samples isolated from tongue, cheek, and subgingival sulcus in edentulous newborns and children with mixed dentition were monitored by polymerase chain reaction (PCR). was not detected in any site of any subject in the two groups tested. However, was not only found in the 6-13 years age group, but also in edentulous newborns at a relatively high prevalence, indicating non-dentition-related colonization by . , , , , and were found in the oral cavity of most subjects belonging to the 6-13 years age group compared to newborns. This suggested a pronounced association between these colonizing bacteria and the presence of teeth. There was also a strong relation between and for their prevalence in the subgingival sulcus of the 6-13 years age group ( < 0.0001), but not in the other sites tested, suggesting that the colonization of dentition-related may be associated with the increased prevalence of non-dentition-related in the subgingival sulcus. Overall, these results suggest that dentition is a key determinant of bacterial colonization, especially orange complex bacteria and the red complex bacterium . C1 [Cortelli, J. R.] Univ Taubate, Dept Periodontol & Prevent Dent, Dent Res Div, BR-12020040 Taubate, SP, Brazil. [Fernandes, C. B.] Univ Taubate, Dept Periodontol, Dent Res Div, BR-12020040 Taubate, SP, Brazil. [Costa, F. O.] Univ Fed Minas Gerais, Dept Periodontol, Sch Dent, BR-31270901 Belo Horizonte, MG, Brazil. [Cortelli, S. C.] Univ Taubate, Nucleus Periodontolal Res, Dent Res Div, BR-12020040 Taubate, SP, Brazil. [Kajiya, M.] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA. [Howell, S. C.] Harvard Univ, Dept Oral Med Infect & Immun, Sch Dent Med, Boston, MA 02115 USA. [Kawai, T.] Harvard Univ, Div Endodont, Sch Dent Med, Boston, MA 02115 USA. RP Cortelli, JR (reprint author), Univ Taubate, Dept Periodontol & Prevent Dent, Dent Res Div, 51 Visconde Rio Branco, BR-12020040 Taubate, SP, Brazil. EM jrcortelli@uol.com.br FU Sao Paulo Foundation for Research [04/00256-6]; National Council for Scientific and Technological Development (CNPq); National Institutes of Health [RO1 DE18499]; Harvard Catalyst Pilot Grant FX The authors are grateful to the Sao Paulo Foundation for Research (grant, 04/00256-6), the National Council for Scientific and Technological Development (CNPq), the National Institutes of Health (grant, RO1 DE18499), and the Harvard Catalyst Pilot Grant. NR 26 TC 7 Z9 7 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JUN PY 2012 VL 31 IS 6 BP 1041 EP 1050 DI 10.1007/s10096-011-1405-9 PG 10 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 940GQ UT WOS:000303878400021 PM 21928086 ER PT J AU Liaw, JVP Yun, CH Walker, TG Kalva, SP d'Othee, BJ AF Liaw, Jonathan V. P. Yun, Chun-Ho Walker, T. Gregory Kalva, Sanjeeva P. d'Othee, Bertrand Janne TI Comparison of clinical and MR imaging outcomes after uterine fibroid embolization with Bead Block and Embosphere SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Uterine fibroid embolization ID TRIS-ACRYL GELATIN; POLYVINYL-ALCOHOL MICROSPHERES; ARTERY EMBOLIZATION; PARTICLES; MODEL; LEIOMYOMAS; SHEEP; MULTICENTER AB Purpose: To compare clinical and imaging outcomes after uterine fibroid embolization (UFE) with Embosphere versus Bead Block microspheres. Materials and methods: Our institutional review board approved this HIPAA-compliant study. We conducted a retrospective review of all consecutive UFEs performed for symptomatic uterine fibroids at our academic institution from 2001 to 2008. UFE was performed using Embosphere (n = 70) or Bead Block (n = 55) microspheres. Patient symptoms and MR images were reviewed before and following UFE. The MR images were analyzed for changes in the size and contrast enhancement of the dominant fibroid and the uterus. Results: 125 patients underwent UFE. Pre-treatment characteristics (patient age, presenting symptoms, fibroid location, and volume of the largest fibroid) were similar across groups. Procedure endpoint (near-stasis, reached in 94% of cases), duration, and sedation medication doses were also similar. Clinical follow-up was available in 69 (55%) patients (mean duration: 13.6 months). Of these, 92% had clinical improvement of their main presenting symptom(s) and 3% developed early menopause. MRI follow-up was available in 105 (84%) patients (mean 7.8 months). Mean volume reduction of the largest fibroid was similar after Embosphere (48%) and Bead Block (53%, p = NS). Residual enhancement >= 5% in the dominant fibroid was similarly uncommon after Bead Block (19%) or Embosphere (16%, p = NS). Mean uterine volume reduction was similar across groups (38%); no myometrial infarction occurred. Conclusion: This retrospective study showed no superiority of Embosphere over Bead Block microspheres in terms of clinical and imaging outcomes after UFE. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Liaw, Jonathan V. P.; Yun, Chun-Ho; Walker, T. Gregory; Kalva, Sanjeeva P.; d'Othee, Bertrand Janne] Massachusetts Gen Hosp, Dept Imaging, Div Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. RP Liaw, JVP (reprint author), Univ Texas Houston, Hlth Sci Ctr Houston, Houston, TX 77030 USA. EM jvpliaw@hotmail.com NR 22 TC 3 Z9 5 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD JUN PY 2012 VL 81 IS 6 BP 1371 EP 1375 DI 10.1016/j.ejrad.2011.03.017 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 939LT UT WOS:000303813100050 PM 21439744 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Detecting and Treating Clostridium Difficile Infections in Patients with Inflammatory Bowel Disease SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Inflammatory bowel disease; Clostridium difficile; Crohn disease; Ulcerative colitis ID ANTIBIOTIC-ASSOCIATED DIARRHEA; RISK-FACTORS; PSEUDOMEMBRANOUS ENTERITIS; HYPERVIRULENT STRAIN; TREATMENT STRATEGIES; DIAGNOSTIC YIELD; COLITIS; METRONIDAZOLE; EPIDEMIOLOGY; VANCOMYCIN AB A cohort that appears to be at a higher risk for Clostridium difficile infection (CDI) and particularly vulnerable to the morbidity and mortality associated with it are patients with underlying inflammatory bowel diseases (IBD). Diagnosis requires demonstration of the toxin from a diarrhea stool sample. Mild CDI can be treated with oral metronidazole, whereas severe disease should be treated with oral vancomycin. Management of recurrent CDI remains challenging. Newer drugs are now available that appear to be effective with lower risk of disease recurrence. Specific treatment trials and prospective studies of CDI in patients with IBD are warranted. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org NR 97 TC 13 Z9 13 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2012 VL 41 IS 2 BP 339 EP + DI 10.1016/j.gtc.2012.01.003 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 941HQ UT WOS:000303954700007 PM 22500522 ER PT J AU Rose, DE Tisnado, DM Tao, ML Malin, JL Adams, JL Ganz, PA Kahn, KL AF Rose, Danielle E. Tisnado, Diana M. Tao, May L. Malin, Jennifer L. Adams, John L. Ganz, Patricia A. Kahn, Katherine L. TI Prevalence, Predictors, and Patient Outcomes Associated with Physician Co-management: Findings from the Los Angeles Women's Health Study SO HEALTH SERVICES RESEARCH LA English DT Article DE Quality of care; physician practice style; physician co-management; patient ratings of care; breast cancer care; provider network restrictions ID PRIMARY-CARE PHYSICIANS; BREAST-CANCER SURVIVORS; QUALITY-OF-CARE; FINANCIAL INCENTIVES; SPECIALTY-CARE; SYSTEM; SATISFACTION; GENERALIST; INTERFACE; PATTERNS AB Background Physician co-management, representing joint participation in the planning, decision-making, and delivery of care, is often cited in association with coordination of care. Yet little is known about how physicians manage tasks and how their management style impacts patient outcomes. Objectives To describe physician practice style using breast cancer as a model. We characterize correlates and predictors of physician practice style for 10 clinical tasks, and then test for associations between physician practice style and patient ratings of care. Methods We queried 347 breast cancer physicians identified by a population-based cohort of women with incident breast cancer regarding care using a clinical vignette about a hypothetical 65-year-old diabetic woman with incident breast cancer. To test the association between physician practice style and patient outcomes, we linked medical oncologists responses to patient ratings of care (physician n = 111; patient n = 411). Results After adjusting for physician and practice setting characteristics, physician practice style varied by physician specialty, practice setting, financial incentives, and barriers to referrals. Patients with medical oncologists who co-managed tasks had higher patient ratings of care. Conclusion Physician practice style for breast cancer is influenced by provider and practice setting characteristics, and it is an important predictor of patient ratings. We identify physician and practice setting factors associated with physician practice style and found associations between physician co-management and patient outcomes (e.g., patient ratings of care). C1 [Rose, Danielle E.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. [Tisnado, Diana M.; Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Tao, May L.] Ctr Radiat Therapy Beverly Hills, Beverly Hills, CA USA. [Adams, John L.] RAND Corp, Santa Monica, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. RP Rose, DE (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM droseash@gmail.com FU California Breast Cancer Research program [7PB-0126S]; National Cancer Institute; Agency for Health Care Research and Quality [1-R01-CA81338-01A1]; University of California, Los Angeles; Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA [P30-AG021684]; UCLA; National Cancer Institute [R25 CA087949] FX This research was funded by the California Breast Cancer Research program grant 7PB-0126S and the National Cancer Institute and the Agency for Health Care Research and Quality grant 1-R01-CA81338-01A1. Dr. Tisnado received support from the University of California, Los Angeles, Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA Grant P30-AG021684, and the content does not necessarily represent the official views of the NIA or the NIH. Dr. Rose received support from the UCLA Cancer Education and Career Development Program, National Cancer Institute grant R25 CA087949. We thank the two anonymous referees for suggestions that significantly strengthened the analyses. We acknowledge Diane Fitzpatrick and Ann Zisser for their data collection efforts (under supervision); Fang Ashlee Hu for programming and data management, and Judith Magee for administrative support. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 47 TC 4 Z9 4 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2012 VL 47 IS 3 BP 1091 EP 1116 DI 10.1111/j.1475-6773.2011.01359.x PN 1 PG 26 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 939HN UT WOS:000303800200012 PM 22171977 ER PT J AU Astrakas, LG Naqvi, SHA Kateb, B Tzika, AA AF Astrakas, Loukas G. Naqvi, Syed Hassan Abbas Kateb, Babak Tzika, A. Aria TI Functional MRI using robotic MRI compatible devices for monitoring rehabilitation from chronic stroke in the molecular medicine era (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE stroke; stroke biomarkers; rehabilitation; functional MR imaging; robotic MRI compatible devices ID INDUCED MOVEMENT THERAPY; CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; CORTICOSPINAL TRACT INTEGRITY; RECOVERY FOLLOWING STROKE; MAGNETIC-RESONANCE; MOTOR RECOVERY; UPPER-LIMB; CORTICAL ACTIVATION; BRAIN PLASTICITY AB The number of individuals suffering from stroke is increasing daily, and its consequences are a major contributor to invalidity in today's society. Stroke rehabilitation is relatively new, having been hampered from the longstanding view that lost functions were not recoverable. Nowadays, robotic devices, which aid by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain which can be monitored by MRI. Multiparametric magnetic resonance imaging (MRI) of stroke patients participating in a training program with a novel Magnetic Resonance Compatible Hand-Induced Robotic Device (MR_CHIROD) could yield a promising biomarker that, ultimately, will enhance our ability to advance hand motor recovery following chronic stroke. Using state-of-the art MRI in conjunction with MR_CHIROD-assisted therapy can provide novel biomarkers for stroke patient rehabilitation extracted by a meta-analysis of data. Successful completion of such studies may provide a ground breaking method for the future evaluation of stroke rehabilitation therapies. Their results will attest to the effectiveness of using MR-compatible hand devices with MRI to provide accurate monitoring during rehabilitative therapy. Furthermore, such results may identify biomarkers of brain plasticity that can be monitored during stroke patient rehabilitation. The potential benefit for chronic stroke patients is that rehabilitation may become possible for a longer period of time after stroke than previously thought, unveiling motor skill improvements possible even after six months due to retained brain plasticity. C1 [Astrakas, Loukas G.; Naqvi, Syed Hassan Abbas; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. [Astrakas, Loukas G.; Naqvi, Syed Hassan Abbas; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. [Astrakas, Loukas G.] Univ Ioannina, Dept Med Phys, GR-45110 Ioannina, Greece. [Tzika, A. Aria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kateb, Babak; Tzika, A. Aria] Brain Mapping Fdn, W Hollywood, CA 90046 USA. [Naqvi, Syed Hassan Abbas] Dow Univ Hlth Sci, Dow Med Coll, Karachi 74200, Pakistan. [Kateb, Babak] Soc Brain Mapping & Therapeut SBMT, W Hollywood, CA 90048 USA. [Kateb, Babak] Natl Ctr Nanobioelect NCNBE, Moffett Field, CA 94035 USA. [Kateb, Babak] Cedars Sinai Med Ctr, Dept Neurosurg, Maxine Dunitz Neurosurg Inst, Los Angeles, CA 90048 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu RI Astrakas, Loukas/F-5918-2011 FU National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [R21 EB004665-01A2] FX This study was supported in part by a grant from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Grant no. R21 EB004665-01A2) to T.A.A. We thank Dr C. Mavroidis the principal investigator of the subcontract to Northeastern University to build the MR_CHIROD. We thank Ann Power Smith, Ph.D. of Write Science Right for editorial assistance. Finally, we thank the Brain Mapping Foundation and Society for Brain Mapping and Therapeutics (SBMT) for their contributions to this research. NR 168 TC 5 Z9 5 U1 2 U2 9 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JUN PY 2012 VL 29 IS 6 BP 963 EP 973 DI 10.3892/ijmm.2012.942 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 939CW UT WOS:000303785700001 PM 22426741 ER PT J AU Nakamura-Palacios, EM Benevides, MCD Zago-Gomes, MD de Oliveira, RWD de Vasconcellos, VF de Castro, LNP da Silva, MC Ramos, PA Fregni, F AF Nakamura-Palacios, Ester Miyuki de Almeida Benevides, Marcelo Campos Zago-Gomes, Maria da Penha Dias de Oliveira, Roney Welinton de Vasconcellos, Vitor Fiorin Passos de Castro, Lais Norberto da Silva, Morgana Croce Ramos, Paula Amorim Fregni, Felipe TI Auditory event-related potentials (P3) and cognitive changes induced by frontal direct current stimulation in alcoholics according to Lesch alcoholism typology SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Alcoholism; FAB; Lesch's typology; P3; tDCS ID PREFRONTAL CORTEX; DOUBLE-BLIND; PARKINSONS-DISEASE; BRAIN-STIMULATION; CONTROLLED TRIAL; CEREBRAL CORTEX; WORKING-MEMORY; DRUG-ADDICTION; MOTOR CORTEX; CONSUMPTION AB Frontal lobe dysfunction is a hallmark of alcohol dependence. Recent studies have shown that a simple but powerful technique of cortical modulation - transcranial direct current stimulation (tDCS) - can induce significant cognitive changes. We therefore aimed to assess the clinical and electrophysiological (as indexed by P3) effects of tDCS of left dorsolateral prefrontal cortex (DLPFC) in different types of alcoholic patients according to Lesch's typology. We enrolled 49 alcoholic subjects, aged between 18 and 75 yr, during the subacute abstinence period to participate in this study. Subjects underwent event-related potential (ERP) registration of alcohol-related and neutral sounds before, during and after active tDCS (1 mA, 35 cm(2), during 10 min) or sham procedure in a counterbalanced and randomized order. Frontal assessment battery (FAB) and five items of the Obsessive Compulsive Drinking Scale were applied at the beginning and at the end of each experimental session. ERP analysis showed an increase in the mean amplitude of P3 associated with alcohol-related sounds after tDCS. This effect was not seen for neutral sounds. This change was more pronounced in Lesch IV alcoholics. Secondary exploratory analysis showed a significant improvement of FAB performance after active tDCS compared to sham tDCS in Lesch IV alcoholics only. We showed clinical and electrophysiological evidence of tDCS-induced frontal activity enhancement that was specific for Lesch IV alcoholics. Given that frontal dysfunction may contribute to the loss of control over drinking behaviour, local increase in frontal activity induced by tDCS might have a beneficial clinical impact in the future. C1 [Nakamura-Palacios, Ester Miyuki] Univ Fed Espirito Santo, Lab Cognit Sci & Neuropsychopharmacol, Programa Posgrad Ciencias Fisiol, Ctr Ciencias Saude,Dept Physiol Sci, BR-29042755 Vitoria, ES, Brazil. [Zago-Gomes, Maria da Penha; de Vasconcellos, Vitor Fiorin] Univ Fed Espirito Santo, Hlth Sci Ctr, Dept Internal Med, BR-29042755 Vitoria, ES, Brazil. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spauding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Nakamura-Palacios, EM (reprint author), Univ Fed Espirito Santo, Lab Cognit Sci & Neuropsychopharmacol, Programa Posgrad Ciencias Fisiol, Ctr Ciencias Saude,Dept Physiol Sci, Av Marechal Campos 1468, BR-29042755 Vitoria, ES, Brazil. EM ester.palacios@terra.com.br FU Fundacao de Apoio a Ciencia e Tecnologia do Espirito Santo (FAPES) FX We are grateful to all patients and their relatives who agreed to participate in this study. We thank the graduate students of the Medical School of the Federal University of Espirito Santo for their help in collecting data. Funding for this study was provided by Fundacao de Apoio a Ciencia e Tecnologia do Espirito Santo (FAPES). NR 52 TC 26 Z9 27 U1 2 U2 11 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 2012 VL 15 IS 5 BP 601 EP 616 DI 10.1017/S1461145711001040 PG 16 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 940MZ UT WOS:000303895000003 PM 21781352 ER PT J AU Song, JY Jo, HH Kim, MR Lew, YO Ryu, KS Cha, JH Kang, CS Donahoe, PK MacLaughlin, DT Kim, JH AF Song, Jae Yen Jo, Hyun Hee Kim, Mee Ran Lew, Young Oak Ryu, Ki Sung Cha, Jung Ho Kang, Chang Suk Donahoe, Patricia K. MacLaughlin, David T. Kim, Jang Heub TI Expression of Mullerian inhibiting substance type II receptor and antiproliferative effects of MIS on human cervical cancer SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE Mullerian inhibiting substance; anti-Mullerian hormone; Mullerian inhibiting substance type II receptor; cervical cancer; immunohistochemistry; in situ hybridization ID HUMAN OVARIAN-CANCER; TGF-BETA; CELL-GROWTH; IN-VIVO; TRANSDUCTION PATHWAY; HORMONE; IMMUNOASSAY; MECHANISM; BOVINE; TARGET AB This study aimed to analyze expression of Mullerian inhibiting substance type II receptor (MISRII) protein and mRNA in cervical neoplasia, to demonstrate the growth inhibition of cervical cancer cells by administration of highly purified recombinant human Mullerian inhibiting substance (MIS) and, furthermore, to evaluate the clinical significance of MIS as a biological modifier for MIS receptor expressing tumors. Reverse transcriptase polymerase chain reaction (RT-PCR) was used for MISRII mRNA expression, and in situ hybridization and immunohistochemistry were used to observe expression, location of MISRII mRNA and protein, respectively. To demonstrate the effect of MIS on the viability of cervical cancer cells, methyl thiazole tetrazolium (MTT) assay was performed. Flow cytometry was used to evaluate the cell cycle distribution after exposure to MIS in cervical cancer cells, and the annexin-V-FITC staining method was performed to demonstrate apoptosis by MIS in cervical cancer cells. Expression of MISRII protein and mRNA were observed in all normal cervical and cervical carcinoma tissues. There was no significant difference in expression of MISRII protein and MISRII mRNA between normal cervical and cervical carcinoma tissues. MTT assay showed negative correlation between MIS exposure time and the viability of cervical cells (P=0.008). The changes in cell cycle distribution after MIS exposure suggest that MIS plays an important role in inducing cellular apoptosis by causing arrest at the G, phase and increasing cells at sub-G(0)G(1) phase. Annexin-V-FITC staining methods showed that cellular apoptosis was, respectively, 10.44 and 12.89% after 24 and 48 h of MIS exposure in cervical carcinoma cells. There was a negative correlation between cellular survival and MIS exposure time. This study demonstrates that MISRII is present on normal cervical and cervical carcinoma tissues, and MIS shows receptor-mediated antiproliferative effect on cervical cells in vitro. These data suggest that MIS may be used as a biological modifier or therapeutic modulator on MISRII-expressing tumors in the future. C1 [Song, Jae Yen; Jo, Hyun Hee; Kim, Mee Ran; Lew, Young Oak; Ryu, Ki Sung; Kim, Jang Heub] Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, Seoul 137701, South Korea. [Cha, Jung Ho] Catholic Univ Korea, Coll Med, Dept Anat, Seoul 137701, South Korea. [Kang, Chang Suk] Catholic Univ Korea, Coll Med, Dept Clin Pathol, Seoul 137701, South Korea. [Donahoe, Patricia K.; MacLaughlin, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Kim, JH (reprint author), Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, 505 Banpo Dong, Seoul 137701, South Korea. EM janghkim@catholic.ac.kr NR 40 TC 1 Z9 3 U1 1 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 2012 VL 40 IS 6 BP 2013 EP 2021 DI 10.3892/ijo.2012.1370 PG 9 WC Oncology SC Oncology GA 937YK UT WOS:000303699900033 PM 22344630 ER PT J AU Hattangadi, JA Chapman, PH Bussiere, MR Niemierko, A Ogilvy, CS Rowell, A Daartz, J Loeffler, JS Shih, HA AF Hattangadi, Jona A. Chapman, Paul H. Bussiere, Marc R. Niemierko, Andrzej Ogilvy, Christopher S. Rowell, Alison Daartz, Juliane Loeffler, Jay S. Shih, Helen A. TI Planned Two-Fraction Proton Beam Stereotactic Radiosurgery for High-Risk Inoperable Cerebral Arteriovenous Malformations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Cerebral arteriovenous malformation; Proton stereotactic radiosurgery; AVM score; High-risk AVM ID MOTOR CORTEX; BRAIN-STEM; RADIATION; OUTCOMES; THERAPY AB Purpose: To evaluate patients with high-risk cerebral arteriovenous malformations (AVMs), based on eloquent brain location or large size, who underwent planned two-fraction proton stereotactic radiosurgery (PSRS). Methods and Materials: From 1991 to 2009, 59 patients with high-risk cerebral AVMs received two-fraction PSRS. Median nidus volume was 23 cc (range, 1.4-58.1 cc), 70% of cases had nidus volume >= 14 cc, and 34% were in critical locations (brainstem, basal ganglia). Median AVM score based on age, AVM size, and location was 3.19 (range, 0.9-6.9). Many patients had prior surgery or embolization (40%) or prior PSRS (12%). The most common prescription was 16 Gy radiobiologic equivalent (RBE) in two fractions, prescribed to the 90% isodose. Results: At a median follow-up of 56.1 months, 9 patients (15%) had total and 20 patients (34%) had partial obliteration. Patients with total obliteration received higher total dose than those with partial or no obliteration (mean dose, 17.6 vs. 15.5 Gy (RBE), p=0.01). Median time to total obliteration was 62 months (range, 23-109 months), and 5-year actuarial rate of partial or total obliteration was 33%. Five-year actuarial rate of hemorrhage was 22% (95% confidence interval, 12.5%-36.8%) and 14% (n=8) suffered fatal hemorrhage. Lesions with higher AVM scores were more likely to hemorrhage (p=0.024) and less responsive to radiation (p=0.026). The most common complication was Grade 1 headache acutely (14%) and long term (12%). One patient developed a Grade 2 generalized seizure disorder, and two had mild neurologic deficits. Conclusions: High-risk AVMs can be safely treated with two-fraction PSRS, although total obliteration rate is low and patients remain at risk for future hemorrhage. Future studies should include higher doses or a multistaged PSRS approach for lesions more resistant to obliteration with radiation. (C) 2012 Elsevier Inc. C1 [Chapman, Paul H.; Bussiere, Marc R.; Niemierko, Andrzej; Rowell, Alison; Daartz, Juliane; Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Chapman, Paul H.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hattangadi, Jona A.] Harvard Radiat Oncol Program, Boston, MA USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM hshih@partners.org NR 20 TC 11 Z9 11 U1 0 U2 0 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 2012 VL 83 IS 2 BP 533 EP 541 DI 10.1016/j.ijrobp.2011.08.003 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 940VI UT WOS:000303920800033 PM 22099050 ER PT J AU Lapusan, S Vidriales, MB Thomas, X de Botton, S Vekhoff, A Tang, RP Dumontet, C Morariu-Zamfir, R Lambert, JM Ozoux, ML Poncelet, P San Miguel, JF Legrand, O DeAngelo, DJ Giles, FJ Marie, JP AF Lapusan, Simona Vidriales, Maria B. Thomas, Xavier de Botton, Stephane Vekhoff, Anne Tang, Ruoping Dumontet, Charles Morariu-Zamfir, Rodica Lambert, John M. Ozoux, Marie-Laure Poncelet, Philippe San Miguel, Jesus F. Legrand, Ollivier DeAngelo, Daniel J. Giles, Francis J. Marie, Jean-Pierre TI Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Acute myeloid leukemia; Antibody-drug conjugate; Maytansine; Pharmacokinetic; Pharmacodynamic ID CELLS AB The efficacy of anti-CD33 immunoconjugates had been previously demonstrated for gemtuzumab-ozogamicin. AVE9633 is an anti-CD33-maytansine conjugate created by ImmunoGen Inc. Phase I trials of AVE9633 were performed in patients with AML to evaluate tolerability, pharmacokinetics and pharmacodynamics. Three phase I studies of AVE9633 were performed in 54 patients with refractory/relapsed AML, evaluating drug infusion on day 1 of a 21-day cycle (Day 1 study), day 1 and 8 (Day 1/8 study) and day 1, 4 and 7 (Day 1/4/7 study) of a 28-day cycle. Toxicity was mainly allergic reaction during infusion (3 grade 3 bronchospasms). DLT was reached for the D1-D7 schedule at 150 mg/sqm (1 keratitis, 1 liver toxicity), and the MTD was set at 130 mg/sqm for this schedule. In the two other phases I, the DLT was not reached. In the Day 1/8 study, CD33 on peripheral blasts was saturated and down-modulated for doses of 75 mg/m(2) x 2 or higher, which was correlated with WBC kinetics and plasma levels of AVE9633. Decrease of DM4/CD33 ratio on the blasts surface between day 1 and 8 was the rational for evaluating day 1/4/7 schedule. This induced relatively constant DM4/CD33 levels over the first 8 days, however no activity was noted. One CRp, one PR and biological activity in five other patients were observed in this study. The Day 1 and Day 1/4/7 studies were early discontinued because of drug inactivity at doses significantly higher than CD33 -saturating doses. No myelossuppression was observed at any trial of AVE9633. The pharmacokinetics/pharmacodynamics data obtained in these studies will provide very useful information for the design of the next generation of immunoconjugates. C1 [Marie, Jean-Pierre] Hop St Antoine, Dept Hematol, F-75571 Paris 12, France. [Lapusan, Simona; Vekhoff, Anne; Tang, Ruoping; Legrand, Ollivier; Marie, Jean-Pierre] St Antoine Hosp, AP HP, Dept Hematol & Oncol, Paris, France. [Vidriales, Maria B.; San Miguel, Jesus F.] Hosp Univ Salamanca, Serv Haematol, Salamanca, Spain. [Thomas, Xavier; Dumontet, Charles] Hop Edouard Herriot, Dept Hematol, Leukemia Unit, Lyon, France. [de Botton, Stephane] Inst Gustave Roussy, Dept Hematol, Villejuif, France. [Morariu-Zamfir, Rodica; Ozoux, Marie-Laure] Sanofi Aventis, Oncol, Paris, France. [Lambert, John M.] ImmunoGen Inc, Cambridge, MA USA. [Poncelet, Philippe] Biocytex, Marseille, France. [Legrand, Ollivier; Marie, Jean-Pierre] Univ Paris 06, Paris, France. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giles, Francis J.] CTRC, San Antonio, TX USA. RP Marie, JP (reprint author), Hop St Antoine, Dept Hematol, 184 Rue Faubourg St Antoine, F-75571 Paris 12, France. EM jean-pierre.marie@sat.aphp.fr OI SAN MIGUEL, JESUS/0000-0002-9183-4857; Vidriales, Maria-Belen/0000-0001-5049-3673 NR 16 TC 35 Z9 37 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUN PY 2012 VL 30 IS 3 BP 1121 EP 1131 DI 10.1007/s10637-011-9670-0 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 940GT UT WOS:000303878700028 PM 21519855 ER PT J AU Le Cesne, A Yovine, A Blay, JY Delaloge, S Maki, RG Misset, JL Frontelo, P Nieto, A Jiao, JJ Demetri, GD AF Le Cesne, Axel Yovine, Alejandro Blay, Jean-Yves Delaloge, Suzette Maki, Robert G. Misset, Jean-Louis Frontelo, Pilar Nieto, Antonio Jiao, Juhui James Demetri, George D. TI A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Trabectedin; Cancer; Safety; Phase II; Singleagent; Yondelis; ET-743 ID SOFT-TISSUE SARCOMAS; CONTINUOUS INTRAVENOUS-INFUSION; OVARIAN-CANCER; ANTITUMOR-ACTIVITY; ADULT PATIENTS; ECTEINASCIDIN-743 ET-743; NUCLEOTIDE EXCISION; PRETREATED PATIENTS; CHEMOTHERAPY; IFOSFAMIDE AB Purpose To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. Methods This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n=570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n=258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n=304/1,198 cycles). Results The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1-59). Nausea, fatigue and vomiting were the most common trabectedin-related adverse events, reported in >= 20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients. Conclusion Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time. C1 [Le Cesne, Axel; Delaloge, Suzette] Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France. [Yovine, Alejandro; Misset, Jean-Louis] Hop St Louis, Paris, France. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, New York, NY 10021 USA. [Frontelo, Pilar; Nieto, Antonio] PharmaMar Clin R&D, Madrid, Spain. [Jiao, Juhui James] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. RP Le Cesne, A (reprint author), Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France. EM lecesne@igr.fr RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU PharmaMar; Jonhson Johnson FX A Le Cesne and JY Blay have received research support and honoraria from PharmaMar and Jonhson & Johnson. S Delaloge has received honoraria from PharmaMar. GD Demetri has served as scientific consultant for both PharmaMar and Johnson & Johnson, and Dana-Farber/Harvard has received research support for the conduct of clinical trials from both PharmaMar and Johnson & Johnson. RG Maki has received research support from PharmaMar. JL Misset has received research support and honoraria from PharmaMar. A Yovine, P Frontelo and A Nieto are present or former employees in PharmaMar and are stock owners. JJ Jiao is employee in Johnson & Johnson. NR 39 TC 42 Z9 44 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUN PY 2012 VL 30 IS 3 BP 1193 EP 1202 DI 10.1007/s10637-011-9662-0 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 940GT UT WOS:000303878700037 PM 21484250 ER PT J AU Chung, M Newberry, SJ Ansari, MT Yu, WW Wu, H Lee, J Suttorp, M Gaylor, JM Motala, A Moher, D Balk, EM Shekelle, PG AF Chung, Mei Newberry, Sydne J. Ansari, Mohammed T. Yu, Winifred W. Wu, Helen Lee, Jounghee Suttorp, Marika Gaylor, James M. Motala, Aneesa Moher, David Balk, Ethan M. Shekelle, Paul G. TI Two methods provide similar signals for the need to update systematic reviews SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE Evidence-based methodology; Systematic reviews; Comparative effectiveness reviews; Omega-3 fatty acids; Cardiovascular disease risk factors; Cancer; Cognitive function ID OMEGA-3-FATTY-ACIDS; GUIDELINES AB Objective: Apply and compare two methods that identify signals for the need to update systematic reviews, using three Evidence-based Practice Center reports on omega-3 fatty acids as test cases. Study Design and Setting: We applied the RAND method, which uses domain (subject matter) expert guidance, and a modified Ottawa method, which uses quantitative and qualitative signals. For both methods, we conducted focused electronic literature searches of recent studies using the key terms from the original reports. We assessed the agreement between the methods and qualitatively assessed the merits of each system. Results: Agreement between the two methods was "substantial" or better (kappa > 0.62) in three of the four systematic reviews. Overall agreement between the methods was "substantial" (kappa = 0.64, 95% confidence interval [Cl] 0.45-0.83). Conclusion: The RAND and modified Ottawa methods appear to provide similar signals for the possible need to update systematic reviews in this pilot study. Future evaluation with a broader range of clinical topics and eventual comparisons between signals to update reports and the results of full evidence review updates will be needed. We propose a hybrid approach combining the best features of both methods, which should allow efficient review and assessment of the need to update. (C) 2012 Elsevier Inc. All rights reserved. C1 [Chung, Mei; Yu, Winifred W.; Lee, Jounghee; Gaylor, James M.; Balk, Ethan M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts Evidence Based Practice Ctr, Boston, MA 02111 USA. [Newberry, Sydne J.; Wu, Helen; Suttorp, Marika; Motala, Aneesa; Shekelle, Paul G.] So Calif Evidence Based Practice Ctr, RAND Hlth, Santa Monica, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Ansari, Mohammed T.; Moher, David] Univ Ottawa, Evidence Based Practice Ctr, Ottawa Methods Ctr, Clin Epidemiol Program,Ottawa Hosp Res Inst, Ottawa, ON, Canada. RP Chung, M (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts Evidence Based Practice Ctr, Box 63,800 Washington St, Boston, MA 02111 USA. EM mchung1@tuftsmedicalcenter.org OI , /0000-0002-6834-7583; Wu, Helen/0000-0001-7775-5282; Moher , David /0000-0003-2434-4206 FU NHLBI NIH HHS [T32 HL069772] NR 16 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 2012 VL 65 IS 6 BP 660 EP 668 DI 10.1016/j.jclinepi.2011.12.004 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 940PA UT WOS:000303904300011 PM 22464414 ER PT J AU Goodson, JM Haffajee, AD Socransky, SS Kent, R Teles, R Hasturk, H Bogren, A Van Dyke, T Wennstrom, J Lindhe, J AF Goodson, J. Max Haffajee, Anne D. Socransky, Sigmund S. Kent, Ralph Teles, Ricardo Hasturk, Hatice Bogren, Anna Van Dyke, Thomas Wennstrom, Jan Lindhe, Jan TI Control of periodontal infections: A randomized controlled trial I. The primary outcome attachment gain and pocket depth reduction at treated sites SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotics; periodontal disease; periodontal surgery; randomized controlled trial ID GENERALIZED AGGRESSIVE PERIODONTITIS; SUBANTIMICROBIAL DOSE DOXYCYCLINE; TETRACYCLINE FIBER THERAPY; REPOSITIONED FLAP SURGERY; CONTROLLED CLINICAL-TRIAL; SUBGINGIVAL MICROBIOTA; NONSURGICAL TREATMENT; ADULT PERIODONTITIS; MICROBIOLOGICAL PARAMETERS; MULTICENTER EVALUATION AB Objective To compare the treatment outcome of scaling and root planing (SRP) in combination with systemic antibiotics, local antibiotic therapy and/or periodontal surgery. Material and Methods One hundred and eighty-seven patients were assigned to eight groups treated by SRP plus none, one, two or three adjunctive treatments and monitored for 24 similar to months in a randomized controlled clinical trial using a 2 similar to 2 similar to 2 factorial design. Systemic amoxicillin similar to metronidazole (SMA), local tetracycline delivery (LTC) and periodontal surgery (SURG) were evaluated as adjuncts. Changes in clinical attachment level (CAL) and probing pocket depth (PPD) were statistically evaluated by ancova of main effects. Results Effects of adjunctive therapy to SRP were minimal at 3 similar to months. Between 3 and 6 similar to months PPD reduction occurred particularly in patients receiving periodontal surgery. After 6 similar to months, both CAL gain and PPD reduction reached a plateau that was maintained at 24 similar to months in all groups. The 24-month CAL gain was improved by SMA (0.50 similar to mm) while PPD was reduced by SMA (0.51 similar to mm) and SURG (0.36 similar to mm). Smoking reduced CAL gain and PPD reduction. Conclusion Patients receiving adjunctive therapies generally exhibited improved CAL gain and/or PPD reduction when compared with the outcome of SRP alone. Only additive, not synergistic effects of the various adjunctive therapies were observed. C1 [Goodson, J. Max; Haffajee, Anne D.; Socransky, Sigmund S.; Kent, Ralph; Teles, Ricardo] Forsyth Inst, Cambridge, MA USA. [Hasturk, Hatice; Van Dyke, Thomas] Boston Univ, Sch Dent Med, Boston, MA 02215 USA. [Bogren, Anna; Wennstrom, Jan; Lindhe, Jan] Univ Gothenburg, Sahlgrenska Acad, Dept Periodontol, Gothenburg, Sweden. RP Goodson, JM (reprint author), Forsyth Inst, Boston, MA USA. EM MGoodson@forsyth.org FU National Institute of Dental and Craniofacial Research [DE12861, RR025771]; GCRC [RR00533, RR01032] FX J. M. Goodson developed the tetracycline fiber used in this study between 1976 and 1994 when it was introduced. It has not been on the market since 2003. No other participants have any conflict of interest with any of the products tested in this study. This research was supported by the National Institute of Dental and Craniofacial Research grants DE12861 and RR025771, and GCRC funding from RR00533 and RR01032. NR 44 TC 40 Z9 40 U1 0 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JUN PY 2012 VL 39 IS 6 BP 526 EP 536 DI 10.1111/j.1600-051X.2012.01870.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 939XW UT WOS:000303855200004 PM 22512461 ER PT J AU Matura, LA McDonough, A Carroll, DL AF Matura, Lea Ann McDonough, Annette Carroll, Diane L. TI Predictors of Health-Related Quality of Life in Patients With Idiopathic Pulmonary Arterial Hypertension SO JOURNAL OF HOSPICE & PALLIATIVE NURSING LA English DT Article DE health status; idiopathic pulmonary arterial hypertension; quality of life ID REPORTED OUTCOMES; QUESTIONNAIRE; VALIDATION; EMPLOYMENT; GUIDELINES; BOSENTAN; EXERCISE; THERAPY; DISEASE; CAMPHOR AB Idiopathic pulmonary arterial hypertension is a debilitating disease that leads to right ventricular heart failure and death. There is limited research on how this disease affects patients. The purpose of this study was to describe differences in health status, health-related quality of life, and psychological states among functional classes along with predictors of health-related quality of life. A convenience sample of 104 participants with idiopathic pulmonary arterial hypertension was recruited. Participants completed a sociodemographic and clinical data form; Medical Outcomes Study Short-Form 36, US Cambridge Pulmonary Hypertension Outcome Review, and Profile of Mood States surveys. The mean age was 51.9 (SD, 16.6) years, and 81 (78%) were female. Patients with functional class IV had significantly worse self-reported physical health status, health-related quality of life, and psychological distress than the other functional classes. Predictors of health-related quality of life were role-emotional (Medical Outcomes Study Short-Form 36), symptoms and activity (US Cambridge Pulmonary Hypertension Outcome Review), depression (Profile of Mood States), employment, and diuretic and oxygen use, accounting for 86% of the variance. These factors need to be monitored and assessed with patients with idiopathic pulmonary arterial hypertension especially as functional class increases. Effective symptom management is necessary to reduce the negative impact on health-related quality of life. A case study is presented to illustrate these points. C1 [Matura, Lea Ann] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [McDonough, Annette] Univ Massachusetts, Lowell, MA USA. [Carroll, Diane L.] Massachusetts Gen Hosp, Inst Patient Care, Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Matura, LA (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd,Room 322, Philadelphia, PA 19104 USA. EM matura@nursing.upenn.edu FU Bouve College of Health Sciences; Sigma Theta Tau Epsilon Gamma Epsilon FX This study was partially funded by the Bouve College of Health Sciences and Sigma Theta Tau Epsilon Gamma Epsilon. NR 36 TC 7 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1522-2179 J9 J HOSP PALLIAT NURS JI J. Hosp. Palliat. Nurs. PD JUN PY 2012 VL 14 IS 4 BP 283 EP 292 DI 10.1097/NJH.0b013e3182496c04 PG 10 WC Nursing SC Nursing GA 938YG UT WOS:000303768900006 ER PT J AU Gandhi, RT Sax, PE Grinspoon, SK AF Gandhi, Rajesh T. Sax, Paul E. Grinspoon, Steven K. TI Metabolic and Cardiovascular Complications in HIV-Infected Patients: New Challenges for a New Age SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Dept Med, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Dept Med, Ragon Inst, Massachusetts Inst Technol & Harvard, Boston, MA 02114 USA. [Sax, Paul E.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rgandhi@partners.org FU National Institutes of Health [R01 AI066992-04A1, G08LM008830-01, NIH U01 AI 694722, NIH 2P30 AI060354-06]; Harvard University Center for AIDS Research; Bristol-Myers Squibb; Tibotec; Theratechnologies; Amgen FX This work was supported in part by the National Institutes of Health (grant numbers R01 AI066992-04A1 and G08LM008830-01 to R. T. G., NIH U01 AI 694722 to the AIDS Clinical Trials Group, and NIH 2P30 AI060354-06 to the Harvard University Center for AIDS Research). This supplement was supported by the Harvard University Center for AIDS Research and an educational grant from Bristol-Myers Squibb.; R. T. G. has received grant funding from and served on an advisory board for Gilead and has received grant funding from Tibotec. P. E. S. has served as a consultant for Bristol-Myers Squibb. S. G. has received research funding from Theratechnologies, Amgen, and Bristol-Myers Squibb, and has served as a consultant for EMD Serono and for Theratechnologies. NR 8 TC 13 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2012 VL 205 SU 3 BP S353 EP S354 DI 10.1093/infdis/jis202 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942BH UT WOS:000304014000001 PM 22577207 ER PT J AU Lo, J Plutzky, J AF Lo, Janet Plutzky, Jorge TI The Biology of Atherosclerosis: General Paradigms and Distinct Pathogenic Mechanisms Among HIV-Infected Patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; CORONARY ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PROTEASE INHIBITORS; RISK; MACROPHAGES; OBESITY; IMMUNITY AB Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV. C1 [Plutzky, Jorge] Brigham & Womens Hosp, Vasc Dis Prevent Program, Div Cardiovasc Med, Boston, MA 02115 USA. [Lo, Janet] Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, Boston, MA 02114 USA. [Lo, Janet; Plutzky, Jorge] Harvard Univ, Sch Med, Boston, MA USA. RP Plutzky, J (reprint author), Brigham & Womens Hosp, Vasc Dis Prevent Program, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM jplutzky@rics.bwh.harvard.edu FU National Institutes of Health [K23 HL092792, R01 HL048743]; Harvard University Center for AIDS Research; Bristol-Myers Squibb FX This work was supported by the National Institutes of Health (grant numbers K23 HL092792 to J. L. and R01 HL048743 to J. P.). This supplement was supported by the Harvard University Center for AIDS Research and an educational grant from Bristol-Myers Squibb. NR 51 TC 23 Z9 23 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2012 VL 205 SU 3 BP S368 EP S374 DI 10.1093/infdis/jis201 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942BH UT WOS:000304014000004 PM 22577210 ER PT J AU Stanley, TL Grinspoon, SK AF Stanley, Takara L. Grinspoon, Steven K. TI Body Composition and Metabolic Changes in HIV-Infected Patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; REVERSE-TRANSCRIPTASE INHIBITOR; ACTIVE ANTIRETROVIRAL THERAPY; MULTICENTER AIDS COHORT; REGIONAL ADIPOSE-TISSUE; DISEASE RISK-FACTORS; PROTEASE INHIBITOR; INSULIN-RESISTANCE; DIABETES-MELLITUS; FAT DEPOSITION AB As antiretroviral therapy has decreased human immunodeficiency virus (HIV)-associated mortality, cardiometabolic abnormalities have become increasingly apparent in HIV-infected individuals. Many patients treated for HIV infection exhibit body composition changes, including peripheral fat atrophy and visceral lipohypertrophy. In addition, HIV-infected individuals demonstrate a higher prevalence of dyslipidemia, insulin resistance and diabetes, and cardiovascular risk, compared with the general population. Although antiretroviral therapy appears to contribute to some of the cardiometabolic abnormalities in HIV infection, HIV itself, immunologic factors, and lifestyle factors are also important mediators of cardiovascular risk. Treatment strategies for body composition changes and cardiometabolic abnormalities in HIV infection include lifestyle modification, lipid-lowering agents, insulin sensitizers, and treatments to reverse endocrine abnormalities in HIV, including growth hormone-releasing hormone. None of these strategies has comprehensively addressed the abnormalities experienced by this population, however, and further research is needed into combined strategies to improve body composition and ameliorate cardiovascular risk. C1 [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, LON5-207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health [K24 DK064545, R01 DK063639, K23 DK089910]; Mary Fisher Clinical AIDS Research and Education Fund; Harvard Center for AIDS Research; Bristol-Myers Squibb; Theratechnologies; Amgen; Bristol Myers Squibb FX This work was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (grants K24 DK064545 and R01 DK063639 to S. G. and grant K23 DK089910 to T. S.) and the Mary Fisher Clinical AIDS Research and Education Fund. This supplement was supported by the Harvard Center for AIDS Research and an educational grant from Bristol-Myers Squibb.; S. G. has received research funding from Theratechnologies, Amgen, and Bristol Myers Squibb and has served as a consultant for EMD Serono and for Theratechnologies. T. S. certifies no potential conflicts of interest. NR 50 TC 35 Z9 35 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2012 VL 205 SU 3 BP S383 EP S390 DI 10.1093/infdis/jis205 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942BH UT WOS:000304014000006 PM 22577212 ER PT J AU Triant, VA AF Triant, Virginia A. TI HIV Infection and Coronary Heart Disease: An Intersection of Epidemics SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE MYOCARDIAL-INFARCTION; MULTICENTER AIDS COHORT; INTIMA-MEDIA THICKNESS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; PROTEASE INHIBITORS; GENERAL-POPULATION; UNINFECTED INDIVIDUALS AB Patients with human immunodeficiency virus (HIV) infection are at increased risk of developing coronary heart disease (CHD). Although factors potentially contributing to this elevated risk include traditional CHD risk factors and antiretroviral medications, more recent data support a role for inflammatory and immunologic factors as central to a complex mechanism. Decreasing CHD risk among HIV-infected patients is likely to involve modification of inflammatory and immunologic factors through antiretroviral therapy or other novel strategies as well as targeted treatment of traditional CHD risk factors. This review will highlight epidemiologic data investigating the association between HIV and CHD outcomes. An overview of potential mechanistic factors associated with CHD in HIV infection and of strategies for managing CHD risk in HIV-infected patients is also included. Specific cardiovascular and metabolic risk factors, CHD risk prediction, and the immunologic basis for CHD in HIV-infected patients will be discussed in separate reviews. C1 [Triant, Virginia A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Triant, Virginia A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Triant, VA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM vtriant@partners.org FU National Institute of Allergy and Infectious Diseases at the National Institutes of Health [K01AI073109]; Harvard Center for AIDS Research; Bristol Myers-Squibb FX This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant number K01AI073109). This supplement was supported by the Harvard Center for AIDS Research and an educational grant from Bristol Myers-Squibb. NR 50 TC 61 Z9 61 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2012 VL 205 SU 3 BP S355 EP S361 DI 10.1093/infdis/jis195 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942BH UT WOS:000304014000002 PM 22577208 ER PT J AU Algamas-Dimantov, A Davidovsky, D Ben-Ari, J Kang, JX Peri, I Hertz, R Bar-Tana, J Schwartz, B AF Algamas-Dimantov, Anna Davidovsky, Dana Ben-Ari, Julius Kang, Jing X. Peri, Irena Hertz, Rachel Bar-Tana, Jacob Schwartz, Betty TI Amelioration of diabesity-induced colorectal ontogenesis by omega-3 fatty acids in mice SO JOURNAL OF LIPID RESEARCH LA English DT Article DE obesity; diabetes; epithelial cell growth; epithelial cell differentiation; colorectal neoplasia ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; INFLAMMATORY-BOWEL-DISEASE; N-3 FATTY-ACIDS; TRANSCRIPTION FACTOR; METABOLIC SYNDROME; TRANSGENIC MICE; GENE-EXPRESSION; LIGAND-BINDING; CELL-FUNCTION; CANCER AB Postnatal intestinal ontogenesis in an animal model of diabesity may recapitulate morphological and transduction features of diabesity-induced intestinal dysplasia and its amelioration by endogenous (n-3) polyunsaturated fatty acids (PUFA). Proliferation, differentiation, and transduction aspects of intestinal ontogenesis have been studied here in obese, insulin-resistant db/db mice, in fat-1 transgene coding for desaturation of (n-6) PUFA into (n-3) PUFA, in db/db crossed with fat-1 mice, and in control mice. Diabesity resulted in increased colonic proliferation and dedifferentiation of epithelial colonocytes and goblet cells, with increased colonic beta-catenin and hepatocyte nuclear factor (HNF)-4 alpha transcriptional activities accompanied by enrichment in HNF-4 alpha-bound (n-6) PUFA. In contrast, in fat-1 mice, colonic proliferation was restrained, accompanied by differentiation of crypt stem cells into epithelial colonocytes and goblet cells and by decrease in colonic beta-catenin and HNF-4 alpha transcriptional activities, with concomitant enrichment in HNF-4 alpha-bound (n-3) PUFA at the expense of (n-6) PUFA. Colonic proliferation and differentiation, the profile of beta-catenin and HNF-4 alpha-responsive genes, and the composition of HNF-4 alpha-bound PUFA of db/db mice reverted to wild-type by introducing the fat-1 gene into the db/db context. Suppression of intestinal HNF-4 alpha activity by (n-3) PUFA may ameliorate diabesity-induced intestinal ontogenesis and offer an effective preventive modality for colorectal cancer. -Algamas-Dimantov, A., D. Davidovsky, J. Ben-Ari, J. X. Kang, I. Peri, R. Hertz, J. Bar-Tana, and B. Schwartz. Amelioration of diabesity-induced colorectal ontogenesis by omega-3 fatty acids in mice. J. Lipid Res. 2012. 53: 1056-1070. C1 [Algamas-Dimantov, Anna; Davidovsky, Dana; Peri, Irena; Schwartz, Betty] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Inst Biochem Food Sci & Nutr, Jerusalem, Israel. [Ben-Ari, Julius] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Interdept Equipment Facil, Jerusalem, Israel. [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Hertz, Rachel; Bar-Tana, Jacob] Hebrew Univ Jerusalem, Sch Med, Dept Human Nutr & Metab, IL-91010 Jerusalem, Israel. RP Schwartz, B (reprint author), Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Inst Biochem Food Sci & Nutr, Jerusalem, Israel. EM bschwart@agri.huji.ac.il FU Israel Science Foundation [134/06] FX This work was supported by Israel Science Foundation Grant 134/06. NR 50 TC 8 Z9 9 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUN PY 2012 VL 53 IS 6 BP 1056 EP 1070 DI 10.1194/jlr.M021949 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 940SK UT WOS:000303913200003 PM 22357704 ER PT J AU Kopp, RP Stroup, SP Schroeck, FR Freedland, SJ Millard, F Terris, MK Aronson, WJ Presti, JC Amling, CL Kane, CJ AF Kopp, Ryan P. Stroup, Sean P. Schroeck, Florian R. Freedland, Stephen J. Millard, Frederick Terris, Martha K. Aronson, William J. Presti, Joseph C., Jr. Amling, Christopher L. Kane, Christopher J. TI Are Repeat Prostate Biopsies Safe? A Cohort Analysis From the SEARCH Database SO JOURNAL OF UROLOGY LA English DT Article DE biopsy; prostatic neoplasms; prostatectomy; recurrence; diagnosis ID INTRAEPITHELIAL NEOPLASIA; NEEDLE BIOPSIES; HIGH-GRADE; CANCER; PROPHYLAXIS; INFECTION; TRENDS; MEN AB Purpose: Patients question whether multiple biopsy sessions cause worse prostate cancer outcomes. Therefore, we investigated whether there is an association between the number of prior biopsy sessions and biochemical recurrence after radical prostatectomy. Materials and Methods: Men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who underwent radical prostatectomy between 1988 and 2010 after a known number of prior biopsies were included in the analysis. Number of biopsy sessions (range 1 to 8) was examined as a continuous and categorical (1, 2 and 3 to 8) variable. Biochemical recurrence was defined as a prostate specific antigen greater than 0.2 ng/ml, 2 values at 0.2 ng/ml or secondary treatment for an increased prostate specific antigen. The association between number of prior biopsy sessions and biochemical recurrence was analyzed using the Cox proportional hazards model. Kaplan-Meier estimates of freedom from biochemical recurrence were compared among the groups. Results: Of the 2,739 men in the SEARCH database who met the inclusion criteria 2,251 (82%) had only 1 biopsy, 365(13%) had 2 biopsies and 123 (5%) had 3 or more biopsies. More biopsy sessions were associated with higher prostate specific antigen (p < 0.001), greater prostate weight (p < 0.001), lower biopsy Gleason sum (p = 0.01) and more organ confined (pT2) disease (p = 0.017). The Cox proportional hazards model demonstrated no association between number of biopsy sessions as a continuous or categorical variable and biochemical recurrence. Kaplan-Meier estimates of freedom from biochemical recurrence were similar across biopsy groups (log rank p = 0.211). Conclusions: Multiple biopsy sessions are not associated with an increased risk of biochemical recurrence in men undergoing radical prostatectomy. Multiple biopsy sessions appear to select for a low risk cohort. C1 [Kopp, Ryan P.; Stroup, Sean P.; Kane, Christopher J.] Univ Calif San Diego, Div Urol, San Diego, CA 92103 USA. [Stroup, Sean P.; Millard, Frederick; Kane, Christopher J.] Moores UCSD Canc Ctr, Sect Urol Oncol, La Jolla, CA USA. [Stroup, Sean P.; Kane, Christopher J.] Vet Affairs San Diego Med Ctr, Urol Sect, La Jolla, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Schroeck, Florian R.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC USA. [Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. RP Kane, CJ (reprint author), Univ Calif San Diego, Div Urol, 200 W Arbor Dr,8897, San Diego, CA 92103 USA. EM ckane@ucsd.edu OI Terris, Martha/0000-0002-3843-7270; Schroeck, Florian/0000-0002-1860-2611 FU Department of Veterans Affairs; Department of Defense; Prostate Cancer Research Program; NIH [R01CA100938, P50 CA92131-01A1]; Georgia Cancer Coalition; American Urological Association Foundation FX Supported by the Department of Veterans Affairs, the Department of Defense, Prostate Cancer Research Program (SJF), NIH R01CA100938 (WJA), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (WJA), Georgia Cancer Coalition (MKT) and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). Views and opinions of and endorsements by the author(s) do not reflect those of the U.S. Army, U.S. Navy or the Department of Defense. NR 18 TC 5 Z9 5 U1 0 U2 1 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 2012 VL 187 IS 6 BP 2056 EP 2060 DI 10.1016/j.juro.2012.01.083 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 939OK UT WOS:000303821300033 PM 22498218 ER PT J AU Tseng, YD Chen, MH Beard, CJ Martin, NE Orio, PF Loffredo, M Renshaw, AA Choueiri, TK Hu, JC Kantoff, PW D'Amico, AV Nguyen, PL AF Tseng, Yolanda D. Chen, Ming-Hui Beard, Clair J. Martin, Neil E. Orio, Peter F. Loffredo, Marian Renshaw, Andrew A. Choueiri, Toni K. Hu, Jim C. Kantoff, Philip W. D'Amico, Anthony V. Nguyen, Paul L. TI Posttreatment Prostate Specific Antigen Nadir Predicts Prostate Cancer Specific and All Cause Mortality SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; radiotherapy; mortality ID EXTERNAL-BEAM RADIOTHERAPY; SURROGATE END-POINTS; RADIATION-THERAPY; RADICAL PROSTATECTOMY; RANDOMIZED-TRIAL; SURVIVAL; DEATH AB Purpose: We investigated whether the prostate specific antigen nadir predicts prostate cancer specific and all cause mortality in men treated in a randomized trial of radiation with or without 6 months of androgen deprivation therapy. Materials and Methods: The study included 204 men with cT1b-T2bN0M0 prostate adenocarcinoma and at least 1 unfavorable factor, including prostate specific antigen less than 10 to 40 ng/ml, Gleason 7 or greater, or T3 on magnetic resonance imaging. We performed Fine and Gray regression, and Cox multivariable analysis to determine whether an increasing prostate specific antigen nadir was associated with prostate cancer specific and all cause mortality, adjusting for treatment, age, Adult Comorbidity Evaluation 27 score and cancer prognostic factors. Results: At a 6.9-year median followup median prostate specific antigen nadir was 0.7 ng/ml for radiation alone and 0.1 ng/ml for radiation plus androgen deprivation therapy. The prostate specific antigen nadir (adjusted HR 1.18/ng/ml increase, 95% CI 1.07-1.31, p = 0.001) and Gleason 8 or greater (adjusted HR 8.05, 95% CI 1.01-64.05, p = 0.049) significantly predicted increased prostate cancer specific mortality. Moderate/severe comorbidity carried a decreased risk (adjusted HR 0.13, 95% CI 0.02-0.96, p = 0.045). Higher prostate specific antigen nadir (adjusted HR 1.10/ng/ml increase, 95% CI 1.04-1.17), older age (adjusted HR 1.10/year, 95% CI 1.04-1.15) and interaction between comorbidity score and randomization arm (each p < 0.001) increased the all cause mortality risk. Men who achieved a prostate specific antigen nadir of the median value or less had lower estimated prostate cancer specific and all cause mortality at 7 years (3.7% vs 18.3%, p = 0.0005 and 31.5% vs 55.0%, p = 0.002). Conclusions: Posttreatment prostate specific antigen nadir is significantly associated with the risk of prostate cancer specific and all cause mortality after radiation with or without androgen deprivation therapy. A suboptimal prostate specific antigen nadir may identify candidates for earlier intervention to prolong survival. C1 [Tseng, Yolanda D.] Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Beard, Clair J.; Martin, Neil E.; Orio, Peter F.; Loffredo, Marian; D'Amico, Anthony V.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hu, Jim C.] Dana Farber Canc Inst, Dept Urol, Boston, MA 02115 USA. [Beard, Clair J.; Martin, Neil E.; Orio, Peter F.; Choueiri, Toni K.; Hu, Jim C.; Kantoff, Philip W.; D'Amico, Anthony V.; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Beard, Clair J.; Martin, Neil E.; Orio, Peter F.; Choueiri, Toni K.; Hu, Jim C.; Kantoff, Philip W.; D'Amico, Anthony V.; Nguyen, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Tseng, YD (reprint author), Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. EM ydtseng@partners.org RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Prostate Cancer Foundation FX Supported by a Prostate Cancer Foundation Young Investigator Award, David and Cynthia Chapin, and a grant from an anonymous family foundation. NR 17 TC 6 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2012 VL 187 IS 6 BP 2068 EP 2073 DI 10.1016/j.juro.2012.01.073 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 939OK UT WOS:000303821300037 PM 22498212 ER PT J AU Hung, WW Ross, JS Boockvar, KS Siu, AL AF Hung, William W. Ross, Joseph S. Boockvar, Kenneth S. Siu, Albert L. TI Association of Chronic Diseases and Impairments With Disability in Older Adults A Decade of Change? SO MEDICAL CARE LA English DT Article DE chronic disease; impairment; disability; prevalence trends ID VISUAL FUNCTION QUESTIONNAIRE; LATE-LIFE DISABILITY; COGNITIVE IMPAIRMENT; FUNCTIONAL DISABILITY; DIABETES-MELLITUS; WOMENS HEALTH; UNITED-STATES; POPULATION; RETIREMENT; TRENDS AB Background: Little is known about how the relationship between chronic disease, impairment, and disability has changed over time among older adults. Objective: To examine how the associations of chronic disease and impairment with specific disability have changed over time. Research Design: Repeated cross-sectional analysis, followed by examining the collated sample using time interaction variables, of 3 recent waves of the Health and Retirement Study. Subjects: The subjects included 10,390, 10,621 and 10,557 community-dwelling adults aged 65 years and above in 1998, 2004, and 2008. Measurements: Survey-based history of chronic diseases including hypertension, heart disease, heart failure, stroke, diabetes, cancer, chronic lung disease, and arthritis; impairments, including cognition, vision, and hearing; and disability, including mobility, complex activities of daily living (ADL), and self-care ADL. Results: Over time, the relationship of chronic diseases and impairments with disability was largely unchanged; however, the association between hypertension and complex ADL disability weakened from 1998 to 2004 and 2008 [odds ratio (OR) = 1.24; 99% confidence interval (CI), 1.06-1.46; OR = 1.07; 99% CI, 0.90-1.27; OR = 1.00; 99% CI, 0.83-1.19, respectively], as it did for hypertension and self-care disability (OR = 1.32; 99% CI, 1.13-1.54; OR= 0.97; 99% CI, 0.82-1.14; OR = 0.99; 99% CI, 0.83-1.17). The association between diabetes and self-care disability strengthened from 1998 to 2004 and 2008 (OR = 1.21; 99% CI, 1.01-1.46; OR = 1.37; 99% CI, 1.15-1.64; OR = 1.52; 99% CI, 1.29-1.79), as it also did for lung disease and self-care disability (OR = 1.64; 99% CI, 1.33-2.03; OR = 1.63; 99% CI, 1.32-2.01; OR = 2.11; 99% CI, 1.73-2.57). Conclusions: Although relationships between diseases, impairments, and disability were largely unchanged, disability became less associated with hypertension and more with diabetes and lung disease. C1 [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters VA Hlth Serv Res & Dev Res Enhance, Bronx, NY USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM william.hung@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU John A Hartford Foundation Center of Excellence; New York Academy of Medicine; National Institute on Aging [K08 AG032886, U01AG009740]; American Federation of Aging Research; Greenwall Foundation FX W.W.H. is a John A Hartford Foundation Center of Excellence Scholar and a New York Academy of Medicine Hoar Fellow. J.S.R. is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. K. S. B. is supported by the Greenwall Foundation. The Health and Retirement Study is sponsored by the National Institute on Aging (grant number U01AG009740) and conducted by the Institute for Social Research at the University of Michigan. NR 35 TC 20 Z9 22 U1 2 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 2012 VL 50 IS 6 BP 501 EP 507 DI 10.1097/MLR.0b013e318245a0e0 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 941ST UT WOS:000303985900006 PM 22584885 ER PT J AU Okunseri, C Okunseri, E Thorpe, JM Xiang, Q Szabo, A AF Okunseri, Christopher Okunseri, Elaye Thorpe, Joshua M. Xiang, Qun Szabo, Aniko TI Medications Prescribed in Emergency Departments for Nontraumatic Dental Condition Visits in the United States SO MEDICAL CARE LA English DT Article DE dental care; dental service utilization; emergency service; medications ID ETHNIC DISPARITIES; CARE; ANALGESIA; PAIN; MANAGEMENT; PATIENT AB Background: Prior research has documented factors associated with nontraumatic dental condition (NTDC) visits to emergency departments (EDs), but little is known about the care received by patients in EDs for NTDC visits. Objective: We examined national trends in prescription of analgesics and antibiotics in EDs for NTDC visits in the United States. Research Design: We analyzed data from the National Hospital Ambulatory Medical Care survey from 1997 to 2007. We used a multivariable logistic regression model to examine factors associated with receiving analgesics and antibiotics for NTDC visits in EDs. Results: Overall 74% received at least 1 analgesic, 56% received at least 1 antibiotic, and 13% received no medication at all during NTDC visits to EDs. The prescription of medications at EDs for NTDC visits steadily increased over time for analgesics (odds ratio = 1.11/y, P < 0.0001) and antibiotics (odds ratio = 1.06/y,P < 0.0001). In the multivariable analysis, self-pay patients had significantly higher adjusted odds of receiving antibiotics, whereas those with nondental reasons for visits and children (0-4 y) had significantly lower adjusted odds of receiving a prescription for antibiotics in EDs for NTDC visits. Children (0-4 y), adults (53-72 y), and older adults (73 y and older) had lower adjusted odds (P < 0.001) of receiving analgesics. Conclusions: Nationally, analgesic and antibiotic prescriptions for NTDC visits to EDs have increased substantially over time. Selfpay patients had significantly higher odds of being prescribed antibiotics. Adults over 53 years and especially those 73 years and older had significantly lower odds of receiving analgesics in EDs for NTDC visits. C1 [Okunseri, Christopher; Okunseri, Elaye] Marquette Univ, Dept Clin Serv, Sch Dent, Milwaukee, WI 53201 USA. [Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Joshua M.] Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Xiang, Qun; Szabo, Aniko] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. RP Okunseri, C (reprint author), Marquette Univ, Dept Clin Serv, Sch Dent, Room 356,POB 1881, Milwaukee, WI 53201 USA. EM christopher.okunseri@mu.edu RI Szabo, Aniko/F-9656-2012; Thorpe, Joshua/C-1188-2013 FU National Institute of Health [1R15DE021196-01] FX Supported by the National Institute of Health Grant #1R15DE021196-01. The authors declare no conflict of interest. NR 25 TC 19 Z9 19 U1 0 U2 1 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 2012 VL 50 IS 6 BP 508 EP 512 DI 10.1097/MLR.0b013e318245a575 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 941ST UT WOS:000303985900007 PM 22584886 ER PT J AU Kelly, PJ Mannarino, E Lewis, JH Baldini, EH Hacker, FL AF Kelly, Paul J. Mannarino, Edward Lewis, John Henry Baldini, Elizabeth H. Hacker, Fred L. TI Total dural irradiation: RapidArc versus static-field IMRT: A case study SO MEDICAL DOSIMETRY LA English DT Article DE IMRT; RapidArc; Dural irradiation; Scalp; Collimator angle ID TOTAL SCALP IRRADIATION; HELICAL TOMOTHERAPY; RADIOTHERAPY; THERAPY; CANCER; BRACHYTHERAPY AB The purpose of this study was to compare conventional fixed-gantry angle intensity-modulated radiation therapy (IMRT) with RapidArc for total dural irradiation. We also hypothesize that target volume-individualized collimator angles may produce substantial normal tissue sparing when planning with RapidArc. Five-, 7-, and 9-field fixed-gantry angle sliding-window IMRT plans were generated for comparison with RapidArc plans. Optimization and normal tissue constraints were constant for all plans. All plans were normalized so that 95% of the planning target volume (PTV) received at least 100% of the dose. RapidArc was delivered using 350 clockwise and counterclockwise arcs. Conventional collimator angles of 45 and 315 were compared with 90 on both arcs. Dose prescription was 59.4 Gy in 33 fractions. PTV metrics used for comparison were coverage, V-107%, D1%, conformality index (CI95%), and heterogeneity index (D-5%-D-95%). Brain dose, the main challenge of this case, was compared using D-1%, Dmean, and V-5 Gy. Dose to optic chiasm, optic nerves, globes, and lenses was also compared. The use of unconventional collimator angles (90 on both arcs) substantially reduced dose to normal brain. All plans achieved acceptable target coverage. Homogeneity was similar for RapidArc and 9-field IMRT plans. However, heterogeneity increased with decreasing number of IMRT fields, resulting in unacceptable hotspots within the brain. Conformality was marginally better with RapidArc relative to IMRT. Low dose to brain, as indicated by V5Gy, was comparable in all plans. Doses to organs at risk (OARs) showed no clinically meaningful differences. The number of monitor units was lower and delivery time was reduced with RapidArc. The case-individualized RapidArc plan compared favorably with the 9-field conventional IMRT plan. In view of lower monitor unit requirements and shorter delivery time, RapidArc was selected as the optimal solution. Individualized collimator angle solutions should be considered by RapidArc dosimetrists for OARs dose reduction. RapidArc should be considered as a treatment modality for tumors that extensively involve in the skull, dura, or scalp. (C) 2012 Published by Elsevier Inc. on behalf of American Association of Medical Dosimetrists. C1 [Kelly, Paul J.; Mannarino, Edward; Lewis, John Henry; Baldini, Elizabeth H.; Hacker, Fred L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. RP Kelly, PJ (reprint author), Cork Univ Hosp, Dept Radiotherapy, Cork, Cork, Ireland. EM paulj.kelly@hse.ie OI Hacker, Fred/0000-0001-7535-7598 NR 20 TC 5 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 J9 MED DOSIM JI Med. Dosim. PD SUM PY 2012 VL 37 IS 2 BP 175 EP 181 DI 10.1016/j.meddos.2011.06.008 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 941HV UT WOS:000303955200012 PM 21862313 ER PT J AU Haas, NB Lin, XY Manola, J Pins, M Liu, G McDermott, D Nanus, D Heath, E Wilding, G Dutcher, J AF Haas, Naomi B. Lin, Xinyi Manola, Judith Pins, Michael Liu, Glenn McDermott, David Nanus, David Heath, Elisabeth Wilding, George Dutcher, Janice TI A phase II trial of doxorubicin and gemcitabine in renal cell carcinoma with sarcomatoid features: ECOG 8802 SO MEDICAL ONCOLOGY LA English DT Article DE Sarcomatoid; Gemcitabine; Doxorubicin; Renal cell cancer; Kidney cancer ID HISTOLOGIC SUBTYPES; EXPRESSION; CANCER; CHEMOTHERAPY; EXPERIENCE; TUMORS AB Sarcomatoid features can arise in renal cell carcinoma of any subtype and are associated with a poor prognosis. Doxorubicin and gemcitabine in a limited series showed activity in aggressive renal tumors and we wished to formally assess the combination in patients with renal cell carcinoma specifically containing sarcomatoid features. The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial of doxorubicin 50 mg/m(2) IV push and gemcitabine 1,500 mg/m(2) IV over 30 min every 2 weeks in 39 patients with locally advanced or metastatic renal cell carcinoma with sarcomatoid features. Ten patients (26%) had grade 3 toxicity, and four patients (11%) had grade 4 toxicities. Although most toxicity was from myelosuppression, one patient died on study from cardiac dysfunction after a cumulative dose of 450 mg/m(2) doxorubicin. Six (16%) patients experienced responses (5 partial responses and 1 complete response), and ten (26%) patients had stable disease. In addition, another patient had an unconfirmed partial response and an additional patient experienced over 50% decrease in her tumor burden after an initial progression. The median overall survival was 8.8 months, and the median progression-free survival was 3.5 months. We conclude that the combination of doxorubicin and gemcitabine, inactive in patients with mostly clear cell histology, demonstrated responses in patients with RCC with sarcomatoid features. We acknowledge the toxicity of this combination but note that limited treatment options exist for this aggressive histology. Only through prospective multicenter trials with comprehensive central pathology review will better treatment options be identified. C1 [Haas, Naomi B.] Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Lin, Xinyi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pins, Michael] Univ Illinois, Chicago Coll Med, Advocate Lutheran Gen Hosp, Park Ridge, IL USA. [Liu, Glenn; Wilding, George] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nanus, David] New York Presbyterian Hosp, New York, NY USA. [Heath, Elisabeth] Karmanos Canc Ctr Inst, Detroit, MI USA. [Dutcher, Janice] St Lukes Roosevelt Hosp, Continuum Canc Ctr, Div Hematol Oncol, New York, NY USA. RP Haas, NB (reprint author), Abramson Canc Ctr, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM naomi.haas@uphs.upenn.edu FU NCI NIH HHS [U10 CA066636, U10 CA023318, U10 CA021076, U10 CA021115, U24 CA114737] NR 29 TC 37 Z9 39 U1 1 U2 5 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 2012 VL 29 IS 2 BP 761 EP 767 DI 10.1007/s12032-011-9829-8 PG 7 WC Oncology SC Oncology GA 935RX UT WOS:000303539000057 PM 21298497 ER PT J AU Ran, CZ Moore, A AF Ran, Chongzhao Moore, Anna TI Spectral Unmixing Imaging of Wavelength-Responsive Fluorescent Probes: An Application for the Real-Time Report of Amyloid Beta Species in Alzheimer's Disease SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Spectral unmixing; Alzheimer's disease; Wavelength-responsive fluorescent probe ID IN-VIVO; CELLS; OLIGOMERS; PEPTIDE; LIGHT; RED AB The goal of the study was to investigate a method for the real-time assessment of a target concentration using a combination of a spectral unmixing technique and a fluorescent probe specific for amyloid beta (A beta) species, the biomarkers for Alzheimer's disease (AD). The probe CRANAD-3 has a significant emission wavelength shift upon binding to A beta species. It was used to differentiate a bound probe from an unbound probe in a phantom, in brain slices and whole brain, and in a transgenic mouse model of AD. The unmixing imaging of AD brain clearly showed differential distribution of the bound and unbound probes between the brain tissue and blood vessels. The unmixed signals of bound CRANAD-3 reached a plateau with increasing dosage, demonstrating that these signals correspond to A beta content, not probe injected dose. This study provided evidence that signals processed by the spectral unmixing technique could be used as a real-time reporter of A beta species loading and . C1 [Ran, Chongzhao; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Mol Imaging Lab Dept Radiol, Boston, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Mol Imaging Lab Dept Radiol, Room 2301,Bldg 149, Boston, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU [K25AG036760] FX This work was supported in part by K25AG036760 award to C. R. We would like to thank Marytheresa Ifediba for proofreading this manuscript. NR 20 TC 10 Z9 10 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2012 VL 14 IS 3 BP 293 EP 300 DI 10.1007/s11307-011-0501-7 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 940IY UT WOS:000303884400004 PM 21739354 ER PT J AU Sembajwe, G Wahrendorf, M Siegrist, J Sitta, R Zins, M Goldberg, M Berkman, L AF Sembajwe, Grace Wahrendorf, Morten Siegrist, Johannes Sitta, Remi Zins, Marie Goldberg, Marcel Berkman, Lisa TI Effects of job strain on fatigue: cross-sectional and prospective views of the job content questionnaire and effort-reward imbalance in the GAZEL cohort SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; PSYCHOSOCIAL WORK-ENVIRONMENT; PSYCHOMETRIC PROPERTIES; MYOCARDIAL-INFARCTION; DECISION LATITUDE; DEPRESSIVE SYMPTOMS; VITAL EXHAUSTION; FRENCH VERSION; RISK-FACTORS; HEALTH AB Objectives The objectives this study were (1) to investigate correlations between measures of psychosocial workplace stress as measured in separate years by the Job Content Questionnaire (JCQ) and Effort-Reward Imbalance (ERI) scales; (2) to establish a valid measure of psychosocial job stress with its components (by identifying the individual and interactive associations of job stress components) and (3) to use the component measures to assess the risk of psychosocial strain at work on fatigue. Methods The JCQ and ERI from the annual survey of the GAZEL cohort established in 1989 initially with 20 624 respondents were used to investigate the associations of workplace stress on mental and physical fatigue in two separate years (1998 and 2006). First, the JCQ measures from separate years (1997 and 1999) were combined to create a measure for the same year as ERI (1998). The new measure was validated for internal and external consistency. Using logistic regression, the subcomponents of stress (upper tertiles of psychological demands, physical demands, decision latitude, social support, effort, reward, ERI and overcommitment) were tested for associations with the highest reporting of mental and physical fatigue. Results By combining JCQ responses from 1997 to 1999, we were able to increase the amount of information available on psychosocial factors in 1998. Psychometric properties of the workplace stress scales also showed expected factor loadings. Workplace psychosocial factors had greater associations with fatigue among men than women. Although psychosocial factors became less predictive of fatigue at 8 years of follow-up, associations between fatigue and psychosocial components (overcommitment, social support and rewards) remained significant. Conclusions These analyses continue to validate the various subcomponents scales of workplace stress as measured by the JCQ and effort-reward imbalance model in GAZEL. They also highlight the importance of psychosocial work factors in the experience of overall fatigue even after an 8-year follow-up. C1 [Sembajwe, Grace; Berkman, Lisa] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sembajwe, Grace] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Sembajwe, Grace; Sitta, Remi; Zins, Marie; Goldberg, Marcel] Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Villejuif, France. [Wahrendorf, Morten; Siegrist, Johannes] Univ Dusseldorf, Inst Med Soziol, D-40225 Dusseldorf, Germany. [Sitta, Remi; Zins, Marie; Goldberg, Marcel] Versailles St Quentin Univ, Versailles, France. [Berkman, Lisa] Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. RP Sembajwe, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM grace_sembajwe@dfci.harvard.edu FU ANR; AFSSET; National Institute on Aging [5U01AG027669-06 /3U01AG027669-05S1]; National Institutes of Health; AFSSET, France; EDF-GDF (Electricite de France-Gaz de France); INSERM (Institut National de la Sante de de la Recherche Me dicale) FX This study was supported by ANR and AFSSET Workage grants, and National Institute on Aging grant #5U01AG027669-06 /3U01AG027669-05S1 for support of LB during this period. Other Funders: National Institutes of Health; l'Agence Nationale de la Recherche (ANR) and AFSSET, France. The GAZEL cohort is funded by grants from EDF-GDF (Electricite de France-Gaz de France) in association with INSERM (Institut National de la Sante de de la Recherche Me dicale). NR 53 TC 13 Z9 13 U1 4 U2 25 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2012 VL 69 IS 6 BP 377 EP 384 DI 10.1136/oem.2010.063503 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 940SH UT WOS:000303912900002 PM 21849345 ER PT J AU Rush, AJ Wisniewski, SR Zisook, S Fava, M Sung, SC Haley, CL Chan, HN Gilmer, WS Warden, D Nierenberg, AA Balasubramani, GK Gaynes, BN Trivedi, MH Hollon, SD AF Rush, A. J. Wisniewski, S. R. Zisook, S. Fava, M. Sung, S. C. Haley, C. L. Chan, H. N. Gilmer, W. S. Warden, D. Nierenberg, A. A. Balasubramani, G. K. Gaynes, B. N. Trivedi, M. H. Hollon, S. D. TI Is prior course of illness relevant to acute or longer-term outcomes in depressed out-patients? A STAR*D report SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Chronic; course of illness; depression; outcomes; recurrent ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; MEASUREMENT-BASED CARE; REPORT QIDS-SR; SELF-REPORT; RELIEVE DEPRESSION; QUICK INVENTORY; RATING-SCALE; RECURRENT DEPRESSION; MAJOR DEPRESSION AB Background. Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes. Method. This cohort study recruited out-patients aged 18-75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as : chronic (index episode >2 years) and recurrent (n=398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n=387). Acute treatment was up to 14 weeks of citalopram (<= 60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR16) <= 5] or response (>= 50% reduction from baseline in QIDS-SR16) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) >= 11]. Results. Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse. Conclusions. Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes. C1 [Rush, A. J.; Sung, S. C.; Haley, C. L.] Duke NUS Grad Med Sch Singapore, Off Clin Sci, Singapore, Singapore. [Wisniewski, S. R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Zisook, S.] Univ Calif San Diego, Dept Psychiat, San Diego VA Med Ctr, San Diego, CA 92103 USA. [Fava, M.; Nierenberg, A. A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Chan, H. N.] Singapore Gen Hosp, Dept Psychiat, Singapore 0316, Singapore. [Gilmer, W. S.; Trivedi, M. H.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Warden, D.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Gaynes, B. N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Hollon, S. D.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Bass Ctr, 6363 Forest Pk Rd,13-354, 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; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH [N01MH90003]; Bristol-Myers Squibb; Forest Laboratories; GlaxoSmithKline; King Pharmaceuticals; Organon; Pfizer; Wyeth; Robert Wood Johnson Foundation; NIMH; Stanley Medical Research Institute; Aspect Medical; PamLab.; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Forest Pharmaceuticals Inc.; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Eli Lilly Company; Lorex Pharmaceuticals; Novartis; Organon Inc.; LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; Janssen Pharmaceutica; Neuronetics; National Institute of Drug Abuse; NARSAD; Cederroth; Cyberonics, Inc.; Lichtwer Pharma; National Alliance for Research in Schizophrenia and Depression, Stanley Foundation; Agency for Healthcare Research and Quality; M-3 Corporation; Ovation Pharmaceuticals; Cephalon, Inc.; Corcept Therapeutics, Inc.; National Alliance for Research in Schizophrenia and Depression; Predix Pharmaceuticals FX This project was funded by the NIMH under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (PI: A.J. Rush). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We appreciate the support of Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth for providing medications at no cost for this trial. We also acknowledge the editorial support of J. Kilner. None of these entities had a role in any part of the study (e.g. design, execution, data collection, analysis, interpretation of the data, writing any report, including this one). Drs Rush and Wisniewski had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.; A.J. Rush: Research support: Robert Wood Johnson Foundation; the NIMH; the Stanley Medical Research Institute. Advisory/consulting: Advanced Neuronetic Systems, Inc.; AstraZeneca; Best Practice Project Management, Inc.; Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals, Inc.; Gerson Lehman Group; GlaxoSmithKline; Healthcare Technology Systems, Inc.; Jazz Pharmaceuticals; Eli Lilly & Company; Magellan Health Services; Merck & Co., Inc.; Neuronetics; Ono Pharmaceutical; Organon USA Inc.; Personality Disorder Research Corp.; Pfizer Inc.; The Urban Institute; and Wyeth-Ayerst Laboratories Inc. Speaking : Cyberonics, Inc.; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Eli Lilly & Company; and Merck & Co., Inc. Equity holdings (exclude mutual funds/blinded trusts): Pfizer Inc. Royalty/patent, other income: Guilford Publications; Healthcare Technology Systems, Inc. S. R. Wisniewski: Research support: NIMH. Advisory/consulting: Cyberonics, Inc. S. Zisook: Research support: NIMH; Aspect Medical; PamLab. Advisory/consulting: GlaxoSmithKline. Speaking: AstraZeneca Pharmaceuticals; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Eli Lilly & Company; Pfizer Inc.; Wyeth Pharmaceuticals. M. Fava: Research support: Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Forest Pharmaceuticals Inc.; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Eli Lilly & Company; Lorex Pharmaceuticals; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories. Advisory/consulting: Aspect Medical Systems; Astra-Zeneca; Bayer AG; Biovail Pharmaceuticals, Inc.; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Grunenthal GmBH; J & J Pharmaceuticals; Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical Company; Eli Lilly & Company; Lundbeck; MedAvante, Inc.; Novartis; Nutrition 21; Organon Inc.; PamLab, LLC; Pfizer Inc.; PharmaStar; Pharmavite; Roche; Sanofi/Synthelabo; Sepracor; Solvay Pharmaceuticals, Inc.; Somerset Pharmaceuticals; Wyeth-Ayerst Laboratories. Speaking: Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Eli Lilly & Company; Novartis; Organon Inc.; Pfizer Inc.; PharmaStar; Wyeth-Ayerst Laboratories. Equity holdings (exclude mutual funds/blinded trusts): Compellis, MedAvante. W. S. Gilmer: Research support: Abbott Laboratories, Aspect Medical; Forest Pharmaceuticals Inc.; Janssen Pharmaceutica; Neuronetics; Novartis; Pfizer Inc.; NIMH. Advisory/consulting: Astra-Zeneca; Bristol-Myers Squibb Company; Eli Lilly & Company; Forest Pharmaceuticals; GlaxoSmithKline; Pfizer, Inc.; Shire. Speaking: Bristol-Myers Squibb Company; Forest Pharmaceuticals; GlaxoSmithKline; Pfizer Inc.; Wyeth-Ayerst Laboratories. D. Warden: Research Support: NIMH, National Institute of Drug Abuse, NARSAD; Equity holdings: Pfizer, Bristol Myers Squib. A. A. Nierenberg: Research support: Bristol-Myers Squibb Company; Cederroth; Cyberonics, Inc.; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Janssen Pharmaceutica; Lichtwer Pharma; Eli Lilly & Company; Pfizer Inc.; NIMH; National Alliance for Research in Schizophrenia and Depression, Stanley Foundation; Wyeth-Ayerst Laboratories.; Advisory/consulting: Bristol-Myers Squibb Company; Eli Lilly & Company; Genaissance; GlaxoSmithKline; Innapharma; Neuronetics; Pfizer, Inc.; Sepracor; Shire. Speaking: Eli Lilly & Company; GlaxoSmithKline; Organon, Inc.; Wyeth-Ayerst Laboratories. B. N. Gaynes: Research support: NIMH; Agency for Healthcare Research and Quality; Robert Wood Johnson Foundation; the M-3 Corporation; Bristol-Myers Squibb Company; Novartis; Pfizer, Inc.; and Ovation Pharmaceuticals. Advisory/consulting: Pfizer, Inc.; Shire Pharmaceuticals; Wyeth-Ayerst. Speaking: GlaxoSmithKline. M. H. Trivedi: Research support: Bristol-Myers Squibb Company; Cephalon, Inc.; Corcept Therapeutics, Inc.; Eli Lilly & Company; GlaxoSmithKline; Janssen Pharmaceutica; NIMH; National Alliance for Research in Schizophrenia and Depression; Pfizer Inc.; Predix Pharmaceuticals; Wyeth-Ayerst Laboratories. Advisory/consulting: Abbott Laboratories, Inc.; Akzo (Organon Pharmaceuticals Inc.); Bayer; Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Pharmacia & Upjohn; Sepracor; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories. Speaking: Akzo (Organon Pharmaceuticals Inc.); Bristol-Myers Squibb Company; Cyberonics, Inc.; Forest Pharmaceuticals; Janssen Pharmaceutica Products, LP; Eli Lilly & Company; Pharmacia & Upjohn; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories. S. D. Hollon: Research support: NIMH. Royalty/patent, other income: Guilford Publications; Wiley. NR 53 TC 20 Z9 20 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUN PY 2012 VL 42 IS 6 BP 1131 EP 1149 DI 10.1017/S0033291711002170 PG 19 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 939PV UT WOS:000303825800002 PM 22008447 ER PT J AU Yu, DK Shi, J Sun, T Du, XL Liu, L Zhang, XJ Lu, C Tang, XH Li, M Xiao, LC Zhang, ZW Yuan, QP Yang, M AF Yu, Dianke Shi, Juan Sun, Tong Du, Xiaoli Liu, Li Zhang, Xiaojiao Lu, Chao Tang, Xiaohu Li, Meng Xiao, Lingchen Zhang, Zhouwei Yuan, Qipeng Yang, Ming TI Pharmacogenetic role of ERCC1 genetic variants in treatment response of platinum-based chemotherapy among advanced non-small cell lung cancer patients SO TUMOR BIOLOGY LA English DT Article DE Chemotherapy; ERCC1; Meta-analysis; Pharmacogenetics; Platinum ID NUCLEOTIDE EXCISION-REPAIR; DNA-REPAIR; POLYMORPHISMS; CISPLATIN; SURVIVAL; XPD; ENDONUCLEASE; METAANALYSIS; ASSOCIATION; EXPRESSION AB The excision repair cross-complementation group 1 (ERCC1) plays an essential role in DNA repair and has been linked to resistance to platinum-based anticancer drugs among advanced non-small cell lung cancer (NSCLC) patients. We systematically evaluate whether ERCC1 Asn118Asn and C8092A genetic variants are associated with treatment response of platinum chemotherapy. We preformed a meta-analysis using ten eligible cohort studies (including 11 data-sets) with a total of 1,252 NSCLC patients to summarize the existing data on the association between the ERCC1 Asn118Asn and C8092A polymorphisms and response to platinum regiments. Odds ratio or hazard ratio with 95% confidence interval were calculated to estimate the correlation. We found that neither ERCC1 C8092A polymorphism nor Asn118Asn variant is associated with different response of platinum-based treatment among advanced NSCLC patients. Additionally, these two genetic variants are not related to treatment response in either Caucasian patients or Asian patients. Our meta-analysis indicates that the ERCC1 Asn118Asn and C8092A polymorphisms may not be good prognostic biomarkers for platinum-based chemotherapy in patients with stage III-IV NSCLC. C1 [Yuan, Qipeng; Yang, Ming] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China. [Yu, Dianke] Chinese Acad Med Sci, State Key Lab Mol Oncol, Dept Etiol & Carcinogenesis, Canc Inst & Hosp, Beijing 100730, Peoples R China. [Yu, Dianke] Peking Union Med Coll, Beijing 100021, Peoples R China. [Shi, Juan; Liu, Li; Zhang, Xiaojiao; Lu, Chao; Tang, Xiaohu; Li, Meng; Xiao, Lingchen; Zhang, Zhouwei; Yuan, Qipeng; Yang, Ming] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing, Peoples R China. [Sun, Tong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sun, Tong] Harvard Univ, Sch Med, Boston, MA USA. [Du, Xiaoli] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Yuan, QP (reprint author), Beijing Univ Chem Technol, Coll Life Sci & Technol, POB 53, Beijing 100029, Peoples R China. EM yuanqp@mail.buct.edu.cn; yangm@mail.buct.edu.cn RI Yang, Ming/G-4705-2012 OI Yang, Ming/0000-0002-7722-7487 FU Beijing Nova Program [2010B013]; Fundamental Research Funds for the Central Universities [ZZ1234]; National Natural Science Foundation of China [30872968] FX This work was supported by Beijing Nova Program (no. 2010B013 to M. Yang), the Fundamental Research Funds for the Central Universities (no. ZZ1234 to M. Yang) and National Natural Science Foundation of China (no. 30872968). NR 29 TC 13 Z9 14 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PD JUN PY 2012 VL 33 IS 3 SI SI BP 877 EP 884 DI 10.1007/s13277-011-0314-y PG 8 WC Oncology SC Oncology GA 935PA UT WOS:000303530200033 PM 22249976 ER PT J AU Genta, RM Sonnenberg, A AF Genta, R. M. Sonnenberg, A. TI Non-Helicobacter pylori gastritis is common among paediatric patients with inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID FOCALLY ENHANCED GASTRITIS; CROHNS-DISEASE; ULCERATIVE-COLITIS; PEPTIC-ULCER; INFECTION; MORTALITY; BIOPSIES; DUODENUM AB Background Helicobacter-negative gastritis and duodenitis occur more often in patients with inflammatory bowel disease (IBD) than in non-IBD controls. Preliminary evidence suggests that they are particularly common among children. Aim To study the age-specific occurrence of gastritis and duodenitis among paediatric IBD patients. Methods From a computerised database of surgical pathology reports, we selected 344 IBD patients and 4241 non-IBD controls between the age 0 and 21 years, who underwent colonoscopy and oesophago-gastro-duodenoscopy with biopsy results from both procedures. Results Helicobacter-negative chronic active gastritis was found in 2% of controls and 20% of IBD patients (Crohn's disease (CD) 26%, ulcerative colitis (UC) 13%). Duodenitis was found in 2% of controls and 17% of IBD patients (Crohn's disease 28%, UC 8%). Similar prevalence rates were observed in male and female patients. The most striking age-specific patterns were seen in Crohn's disease, with chronic active gastritis being highest in the 59 years age-group and declining in all subsequent age-groups. The age-specific rise and fall of duodenitis appeared more protracted, reaching a peak at age 1014 years and then gradually declining. Conclusions Helicobacter-negative gastritis and duodenitis occur significantly more often in paediatric IBD patients than in non-IBD controls, as well as in adult IBD patients. Such upper gastrointestinal inflammation appears to be particularly common in patients with Crohn's disease. C1 [Genta, R. M.] Miraca Life Sci, Irving, TX USA. [Genta, R. M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, R. M.] Dallas VA Med Ctr, Dallas, TX USA. [Sonnenberg, A.] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals FX Declaration of personal interests: Robert M. Genta is employed by Miraca Life Sciences, Irving, TX, USA. Amnon Sonnenberg is supported by a grant from Takeda Pharmaceuticals. NR 22 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JUN PY 2012 VL 35 IS 11 BP 1310 EP 1316 DI 10.1111/j.1365-2036.2012.05090.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 934IF UT WOS:000303437000007 PM 22486730 ER PT J AU Lee, YJ Lee, HJ Choi, SH Jin, YB An, HJ Kang, JH Yoon, SS Lee, YS AF Lee, Yoon-Jin Lee, Hae-Jun Choi, Seo-hyun Jin, Yeung Bae An, Ho Jung Kang, Jin-Hyoung Yoon, Sam S. Lee, Yun-Sil TI Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction SO ANGIOGENESIS LA English DT Article DE Heat shock protein 25/27 (HSPB1); Angiogenic balance; Vascular endothelial growth (VEGF); Endothelial cell (EC) ID ENDOTHELIAL GROWTH-FACTOR; ALPHA-B-CRYSTALLIN; HEAT-SHOCK PROTEINS; TUMOR-GROWTH; CANCER; INHIBITION; KINASE; THROMBOSPONDIN-1; PHOSPHORYLATION; EXPRESSION AB Endothelial cell function is critical for angiogenic balance in both physiological and pathological conditions, such as wound healing and cancer, respectively. We report here that soluble heat shock protein beta-1 (HSPB1) is released primarily from endothelial cells (ECs), and plays a key role in regulating angiogenic balance via direct interaction with vascular endothelial growth factor (VEGF). VEGF-mediated phosphorylation of intracellular HSPB1 inhibited the secretion of HSPB1 and their binding activity in ECs. Interestingly, co-culture of tumor ECs with tumor cells decreased HSPB1 secretion from tumor ECs, suggesting that inhibition of HSPB1 secretion allows VEGF to promote angiogenesis. Additionally, neutralization of HSPB1 in a primary mouse sarcoma model promoted tumor growth, indicating the anti-angiogenic role of soluble HSPB1. Overexpression of HSPB1 by HSPB1 adenovirus was sufficient to suppress lung metastases of CT26 colon carcinoma in vivo, while neutralization of HSPB1 promoted in vivo wound healing. While VEGF-induced regulation of angiogenesis has been studied extensively, these findings illustrate the key contribution of HSPB1-VEGF interactions in the balance between physiological and pathological angiogenesis. C1 [Lee, Yun-Sil] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. [Lee, Yun-Sil] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. [Lee, Yoon-Jin; Lee, Hae-Jun; Choi, Seo-hyun; Jin, Yeung Bae] Korea Inst Radiol & Med Sci, Div Radiat Effects, Seoul 139706, South Korea. [Choi, Seo-hyun] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea. [An, Ho Jung; Kang, Jin-Hyoung] Catholic Univ, Div Med Oncol, Seoul St Marys Hosp, Seoul 137040, South Korea. [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yoon, Sam S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, YS (reprint author), Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. EM yslee0425@ewha.ac.kr OI An, Ho Jung/0000-0003-0821-8365 FU Nuclear Research and Development Program [M2AMA006]; Basic Science Research Program [R1A4A002]; National Research Foundation of Korea (NRF) [2011-0013364]; Korean Ministry of Education, Science, and Technology (MEST) FX We thank Dr. Sandra Ryeom (University of Pennsylvania Medical School) for helpful discussions and Dr. Christiana DelloRusso for assistance editing the manuscript. This work was supported by the Nuclear Research and Development Program (Grant No. M2AMA006), Basic Science Research Program (Grant No. R1A4A002), and Mid-career Researcher Program (Grat No. 2011-0013364) of the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education, Science, and Technology (MEST). NR 42 TC 16 Z9 18 U1 1 U2 15 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JUN PY 2012 VL 15 IS 2 BP 229 EP 242 DI 10.1007/s10456-012-9255-3 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 934TU UT WOS:000303470400005 PM 22350794 ER PT J AU Munshi, MN Maguchi, M Segal, AR AF Munshi, Medha N. Maguchi, Megumi Segal, Alissa R. TI Treatment of Type 2 Diabetes in the Elderly SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetes; Elderly; Treatment, Type 2 ID COGNITIVE DYSFUNCTION; MEDICATION USE; OLDER-ADULTS; MELLITUS; HYPOGLYCEMIA; PATIENT; POPULATION; MANAGEMENT; ADHERENCE; OUTCOMES AB As the number of older adults increases in the United States and worldwide, management of patients with multiple coexisting chronic diseases has become a critical component in health care. Management of diabetes is particularly challenging in this population due to significant risks of microvascular and macrovascular diseases on the one hand, and complications of the treatment strategies (e.g., hypoglycemia) with intensive control on the other hand. To provide a balanced approach to diabetes in the elderly, a comprehensive and holistic strategy, with consideration of overall health, functional status, psychosocial environment, financial resources and, finally but most importantly, quality of life is needed. Understanding the unique challenges faced by older adults with diabetes and issues pertaining to antidiabetes medications with aging is an important first step in the direction of better and tailored care of this burgeoning population. C1 [Munshi, Medha N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Geriatr,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Segal, Alissa R.] Massachusetts Coll Pharm & Hlth Sci, Joslin Diabet Ctr, Dept Pharm Practice, Boston, MA 02215 USA. RP Munshi, MN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Geriatr,Beth Israel Deaconess Med Ctr, 110 Francis St,LMOB 1B, Boston, MA 02215 USA. EM mmunshi@bidmc.harvard.edu; mmaguchi@bidmc.harvard.edu; alissa.segal@mcphs.edu FU Sanofi-Aventis FX M. Munshi: has received grant support from Sanofi-Aventis; M. Maguchi: none; A. Segal: none. NR 31 TC 8 Z9 10 U1 5 U2 15 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD JUN PY 2012 VL 12 IS 3 BP 239 EP 245 DI 10.1007/s11892-012-0269-4 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935JQ UT WOS:000303515400005 PM 22484911 ER PT J AU Phipps, MS Jastreboff, AM Furie, K Kernan, WN AF Phipps, Michael S. Jastreboff, Ania M. Furie, Karen Kernan, Walter N. TI The Diagnosis and Management of Cerebrovascular Disease in Diabetes SO CURRENT DIABETES REPORTS LA English DT Article DE Cerebrovascular disorders; Stroke; Cerebral hemorrhage; Ischemic attack; Transient; Diabetes mellitus; Diagnosis; Therapeutics; Cerebrovascular disease ID TRANSIENT ISCHEMIC ATTACK; ASSOCIATION/AMERICAN-STROKE-ASSOCIATION; HEALTH-CARE PROFESSIONALS; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; AMERICAN-HEART-ASSOCIATION; MULTIPLE LACUNAR INFARCTS; PLACEBO-CONTROLLED TRIAL; IN-HOSPITAL MORTALITY; BLOOD-GLUCOSE CONTROL; HIGH-RISK PATIENTS AB Cerebrovascular disease is a leading cause of morbidity and mortality in diabetes. Compared with nondiabetic patients, diabetic patients have at least twice the risk for stroke, earlier onset of symptoms, and worse functional outcomes. Approximately 20 % of diabetic patients will die from stroke, making it one of the leading causes of death in this population. Effective strategies for primary and secondary prevention of stroke have been developed in research cohorts that included both diabetic and nondiabetic patients. Nevertheless, prevention in diabetes has some specific considerations. In this paper, we summarize evidence to guide the diagnosis and management of stroke in diabetic patients. We propose that diabetic stroke patients should have a robust risk assessment to target interventions, like other patients with cerebrovascular disease, but with special attention to glycemic control and lifestyle modification. C1 [Phipps, Michael S.] VA Connecticut Healthcare Syst, West Haven, CT 06519 USA. [Phipps, Michael S.; Jastreboff, Ania M.] Yale Univ, Sch Med, New Haven, CT 06519 USA. [Furie, Karen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler MGH Stroke Res Ctr, Boston, MA 02114 USA. [Kernan, Walter N.] Yale Univ, Sch Med, New Haven, CT 06525 USA. RP Phipps, MS (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,Mail Code 11-ACSLG, West Haven, CT 06519 USA. EM michael.phipps@yale.edu; ania.jastreboff@yale.edu; kfurie@partners.org; walter.kernan@yale.edu OI Phipps, Michael/0000-0001-8398-5404 FU Takeda Pharmaceuticals North America FX M.S. Phipps: none; A. M. Jastreboff: has received payment for lectures including service on speakers bureaus for Yale Affiliated Hospital Program - providing medical education lectures to hospital in Southern Connecticut; and is a contractor for Pfizer providing clinical services for study volunteers; K. Furie: none; W.N. Kernan: has received grant support from Takeda Pharmaceuticals North America. NR 100 TC 6 Z9 8 U1 2 U2 2 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD JUN PY 2012 VL 12 IS 3 BP 314 EP 323 DI 10.1007/s11892-012-0271-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935JQ UT WOS:000303515400014 PM 22492061 ER PT J AU Sprenger, T Borsook, D AF Sprenger, Till Borsook, David TI Migraine changes the brain: neuroimaging makes its mark SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE functional MRI; migraine; magnetic resonance spectroscopy; PET; voxel-based morphometry ID PERIAQUEDUCTAL GRAY-MATTER; SPREADING DEPRESSION; HEMIPLEGIC MIGRAINE; STEM ACTIVATION; BASAL GANGLIA; HEADACHE; PAIN; ATTACKS; AURA; CORTEX AB Purpose of review This review summarizes key findings of the current literature on functional neuroimaging in migraine and describes how these studies have changed our view of the disorder. Recent findings Recent studies have started not only to investigate the global cerebral activation pattern during migraine attacks, but to address specific aspects of migraine attacks such as photophobia, osmophobia as well as pain perception with the aim of disentangling the underlying mechanisms. There is also more and more evidence that the migraine brain is abnormal even outside of attacks and that repeated attacks are leading to functional and structural alterations in the brain, which may in turn drive the transformation of migraine to its chronic form. Some new results are pinpointing toward a potential role of interesting new brain areas in migraine pathophysiology such as the temporal cortex or the basal ganglia. Summary Neuroimaging studies are beginning to shed light on the mechanisms underlying the development and evolution of migraine and its specific symptoms. Future studies have the potential to also improve our understanding of established and upcoming treatment approaches and to monitor treatment effects in an objective and noninvasive way. C1 [Sprenger, Till] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland. [Sprenger, Till] Univ Basel Hosp, Div Neuroradiol, Dept Radiol & Nucl Med, CH-4031 Basel, Switzerland. [Borsook, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Pain & Brain, Boston, MA USA. [Borsook, David] Harvard Univ, Childrens Hosp, Sch Med, Ctr Pain & Brain, Boston, MA 02115 USA. RP Borsook, D (reprint author), Harvard Univ, Ctr Pain & Brain, Sch Med, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM dborsook@partners.org FU NIH [K24 NS064050 (NINDS), R01 NS056195 (NINDS)] FX We gratefully acknowledge Michaela Andelova, MUDr for help with Table 1. The work was supported by grants from NIH (K24 NS064050 (NINDS) and R01 NS056195 (NINDS) to D.B. NR 85 TC 34 Z9 34 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 2012 VL 25 IS 3 BP 252 EP 262 DI 10.1097/WCO.0b013e3283532ca3 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 935UB UT WOS:000303545600006 PM 22487570 ER PT J AU Hu, JC Williams, SB O'Malley, AJ Smith, MR Nguyen, PL Keating, NL AF Hu, Jim C. Williams, Stephen B. O'Malley, A. James Smith, Matthew R. Nguyen, Paul L. Keating, Nancy L. TI Androgen-Deprivation Therapy for Nonmetastatic Prostate Cancer Is Associated With an Increased Risk of Peripheral Arterial Disease and Venous Thromboembolism SO EUROPEAN UROLOGY LA English DT Article DE Hormonal/adverse effect; Prostatic neoplasms/drug therapy; Peripheral vascular disease; Venous thromboembolism ID CARDIOVASCULAR-DISEASE; BODY-COMPOSITION; SENSITIVITY; SUPPRESSION; CONFOUNDERS; THROMBOSIS; STIFFNESS; HEALTH; MEN AB Background: Previous studies demonstrate that androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and orchiectomy for prostate cancer (PCa) is associated with cardiovascular disease. However, few studies have examined its effect on the peripheral vascular system. Objective: To study the risk of peripheral artery disease (PAD) and venous thromboembolism associated with ADT for PCa. Design, settings, and participants: This was a population-based observational study of 182 757 US men >= 66 yr of age who were diagnosed with nonmetastatic PCa from 1992 to 2007, with a median follow-up of 5.1 yr, of whom 47.8% received GnRH agonists and 2.2% orchiectomy. Measurements: We used Cox proportional hazards models with time-varying treatment variables to adjust for demographic and tumor characteristics in assessing whether treatment with GnRH agonists or orchiectomy were associated with PAD and/or venous thromboembolism. Results and limitations: GnRH agonist use was associated with an increased risk of incident PAD (adjusted hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.12-1.21) and incident venous thromboembolism (adjusted HR: 1.10; 95% CI, 1.04-1.15). In addition, orchiectomy was associated with an increased risk of peripheral arterial disease (adjusted HR: 1.13; 95% CI, 1.02-1.26) and venous thromboembolism (adjusted HR: 1.27; 95% CI, 1.11-1.45). Limitations include the observational study design and the inability to assess the use of oral antiandrogens. Conclusions: ADT for nonmetastatic PCa is associated with an increased risk of PAD and venous thromboembolism. Additional research is needed to better understand the potential risks and benefits of ADT, so that this treatment can be targeted to patients for whom the benefits are clearest. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Hu, Jim C.] Univ Calif Los Angeles, Inst Urol Oncol, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Williams, Stephen B.] Brigham & Womens Hosp, Div Urol, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Dept Hlth Policy, Sch Med, Boston, MA USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Hu, JC (reprint author), Univ Calif Los Angeles, Inst Urol Oncol, Dept Urol, David Geffen Sch Med, 924 Westwood BLVD,STE 1000, Los Angeles, CA 90024 USA. EM jhu2@partners.org FU Prostate Cancer Foundation FX This study was funded by the Prostate Cancer Foundation. NR 29 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JUN PY 2012 VL 61 IS 6 BP 1119 EP 1128 DI 10.1016/j.eururo.2012.01.045 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 934PW UT WOS:000303458000015 PM 22336376 ER PT J AU Konijeti, R Kibel, AS AF Konijeti, Ramdev Kibel, Adam S. TI Androgen Deprivation Therapy for Localized and Nonmetastatic Prostate Cancer: Too Much of a Good Thing? SO EUROPEAN UROLOGY LA English DT Editorial Material C1 [Kibel, Adam S.] Harvard Univ, Div Urol, Dept Surg, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. [Konijeti, Ramdev] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Kibel, AS (reprint author), Harvard Univ, Div Urol, Dept Surg, Brigham & Womens Hosp,Med Sch, 45 Francis St, Boston, MA 02115 USA. EM akibel@partners.org NR 10 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JUN PY 2012 VL 61 IS 6 BP 1129 EP 1130 DI 10.1016/j.eururo.2012.03.002 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 934PW UT WOS:000303458000016 PM 22445550 ER PT J AU Keating, NL Smith, MR Hu, JC AF Keating, Nancy L. Smith, Matthew R. Hu, Jim C. TI Reply from Authors re: Ramdev Konijeti, Adam S. Kibel. Androgen Deprivation Therapy for Localized and Nonmetastatic Prostate Cancer: Too Much of a Good Thing? Eur Urol 2012;61:1129-30 Still Much to Understand About Androgen Deprivation Therapy and Cardiovascular Disease SO EUROPEAN UROLOGY LA English DT Editorial Material ID CLINICAL-TRIALS; PARTICIPATION; MEN; AGE C1 [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. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JUN PY 2012 VL 61 IS 6 BP 1131 EP 1131 DI 10.1016/j.eururo.2012.03.044 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 934PW UT WOS:000303458000017 ER PT J AU Yu, HY Hevelone, ND Lipsitz, SR Kowalczyk, KJ Nguyen, PL Choueiri, TK Kibel, AS Hu, JC AF Yu, Hua-yin Hevelone, Nathanael D. Lipsitz, Stuart R. Kowalczyk, Keith J. Nguyen, Paul L. Choueiri, Toni K. Kibel, Adam S. Hu, Jim C. TI Comparative Analysis of Outcomes and Costs Following Open Radical Cystectomy Versus Robot-Assisted Laparoscopic Radical Cystectomy: Results From the US Nationwide Inpatient Sample SO EUROPEAN UROLOGY LA English DT Article DE Bladder cancer; Cost; Cystectomy; Outcomes; Robotic surgery ID BLADDER-CANCER; PROSTATECTOMY; COMPLICATIONS; SURGERY; EMPHASIS AB Background: Although robot-assisted laparoscopic radical cystectomy (RARC) was first reported in 2003 and has gained popularity, comparisons with open radical cystectomy (ORC) are limited to reports from high-volume referral centers. Objective: To compare population-based perioperative outcomes and costs of ORC and RARC. Design, setting, and participants: A retrospective observational cohort study using the US Nationwide Inpatient Sample to characterize 2009 RARC compared with ORC use and outcomes. Outcome measurements and statistical analysis: Propensity score methods were used to compare inpatient morbidity and mortality, lengths of stay, and costs. Results and limitations: We identified 1444 ORCs and 224 RARCs. Women were less likely to undergo RARC than ORC (9.8% compared with 15.5%, p = 0.048), and 95.7% of RARCs and 73.9% of ORCs were performed at teaching hospitals (p < 0.001). In adjusted analyses, subjects undergoing RARC compared with ORC experienced fewer inpatient complications (49.1% and 63.8%, p = 0.035) and fewer deaths (0% and 2.5%, p < 0.001). RARC compared with ORC was associated with lower parenteral nutrition use (6.4% and 13.3%, p = 0.046); however, there was no difference in length of stay. RARC compared with ORC was $3797 more costly (p = 0.023). Limitations include retrospective design, absence of tumor characteristics, and lack of outcomes beyond hospital discharge. Conclusions: RARC is associated with lower parenteral nutrition use and fewer inpatient complications and deaths. However, lengths of stay are similar, and the robotic approach is significantly more costly. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Dept Urol, Los Angeles, CA 90024 USA. [Yu, Hua-yin; Kibel, Adam S.] Harvard Univ, Brigham & Womens Hosp, Div Urol, Sch Med, Boston, MA 02115 USA. [Hevelone, Nathanael D.; Lipsitz, Stuart R.] Harvard Univ, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Sch Med, Boston, MA 02115 USA. [Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Hu, JC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Dept Urol, 924 Westwood Blvd,Suite 1000, Los Angeles, CA 90024 USA. EM jimhumd@gmail.com OI Hevelone, Nathanael/0000-0003-4740-2085 FU American Urological Association; Robert and Kathy Salipante Minimally-Invasive Urologic Research Fellowship; US Department of Defense [W81XWH-08-1-0283] FX Jim C. Hu certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Dr. Yu receives salary support from the American Urological Association Foundation Research Scholars Award and the Robert and Kathy Salipante Minimally-Invasive Urologic Research Fellowship, and Dr. Hu receives salary support from the US Department of Defense Physician Training Award W81XWH-08-1-0283. NR 32 TC 53 Z9 53 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JUN PY 2012 VL 61 IS 6 BP 1239 EP 1244 DI 10.1016/j.eururo.2012.03.032 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 934PW UT WOS:000303458000040 PM 22482778 ER PT J AU Stephens, CE Newcomer, R Blegen, M Miller, B Harrington, C AF Stephens, Caroline E. Newcomer, Robert Blegen, Mary Miller, Bruce Harrington, Charlene TI Emergency Department Use by Nursing Home Residents: Effect of Severity of Cognitive Impairment SO GERONTOLOGIST LA English DT Article DE cognitive impairment; nursing home; emergency department; hospitalization; ambulatory care-sensitive condition ID MINIMUM DATA SET; FACILITY RESIDENTS; TRANSITIONAL CARE; ADVANCED DEMENTIA; AMBULATORY-CARE; OLDER-PEOPLE; HOSPITALIZATION; HEALTH; DECISIONS; MDS AB To examine the 1-year prevalence and risk of emergency department (ED) use and ambulatory care-sensitive (ACS) ED use by nursing home (NH) residents with different levels of severity of cognitive impairment (CI). We used multinomial logistic regression to estimate the effect of CI severity on the odds of any ED visit and any ACS ED visit in a 2006 national random sample of NH residents, controlling for predisposing, enabling, and need characteristics. Of 132,753 NH residents, 62% had at least one ED visit and approximately 24% had at least one ACS ED visit in 2006. The probability of any ED visit or any ACS ED visit varied with the severity of resident CI. Residents with mild CI had up to15% higher odds of any ED or any ACS ED visit and those with more moderate CI had 9% higher odds of an ACS ED visit compared with those without CI. The probability of any ED visit was negatively associated with advanced dementia (adjusted odds ratio = 0.60; 95% CI = 0.55-0.65). Earlier identification of persons with mild CI may facilitate patient, family, and staff education, as well as advanced care planning to reduce ACS ED visits. Both ACS ED use and hospitalizations, adjusted for case mix, should be used as quality indicators to help ensure greater accountability for high-quality NH care and more appropriate utilization of ED resources. C1 [Stephens, Caroline E.; Newcomer, Robert; Harrington, Charlene] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA 94143 USA. [Stephens, Caroline E.] San Francisco VA Med Ctr, Div Geriatr Palliat & Extended Care, San Francisco, CA USA. [Blegen, Mary] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Miller, Bruce] Univ Calif San Francisco, Dept Community Hlth Syst, San Francisco, CA 94143 USA. RP Stephens, CE (reprint author), Univ Calif San Francisco, Dept Social & Behav Sci, 3333 Calif St,Suite 455, San Francisco, CA 94143 USA. EM caroline.stephens@ucsf.edu NR 42 TC 11 Z9 11 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2012 VL 52 IS 3 BP 383 EP 393 DI 10.1093/geront/gnr109 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 936OM UT WOS:000303599900009 PM 22056961 ER PT J AU Menschikowski, M Hagelgans, A Fuessel, S Mareninova, OA Neumeister, V Wirth, MP Siegert, G AF Menschikowski, Mario Hagelgans, Albert Fuessel, Susanne Mareninova, Olga A. Neumeister, Volker Wirth, Manfred P. Siegert, Gabriele TI Serum Levels of Secreted Group IIA Phospholipase A(2) in Benign Prostatic Hyperplasia and Prostate Cancer: A Biomarker for Inflammation or Neoplasia? SO INFLAMMATION LA English DT Article DE prostate cancer; benign prostatic hyperplasia; secreted phospholipase A(2); C-reactive protein; inflammation ID C-REACTIVE PROTEIN; PROGNOSTIC MARKER; EXPRESSION; DISEASES; RISK; ANTIGEN; INTERLEUKIN-6; ASSOCIATION; INCIDENT; ENZYMES AB Secreted group IIA phospholipase A(2) (sPLA(2)-IIA) is markedly up-regulated in human prostate cancer (PCa) specimens and in some PCa-derived cell lines, indicating an important role of this enzyme in tumourigenesis. In this study, we measured levels of sPLA(2)-IIA, C-reactive protein (CRP), and prostate-specific antigen (PSA) in serum samples obtained from patients with benign prostatic hyperplasia (BPH) and with PCa of different stages. We found that serum levels of sPLA(2)-IIA and CRP in BPH and PCa patients were significantly elevated compared to those of healthy individuals, but the concentrations of these inflammatory biomarkers did not differ between patients with BPH or PCa. Furthermore, serum levels of sPLA(2)-IIA correlated with concentrations of CRP, but not with PSA, Gleason grade or tumour stage. In conclusion, these findings suggest that cancer-related changes are not exclusive factors contributing to elevated serum sPLA(2)-IIA levels and emphasize the utility of sPLA(2)-IIA as a circulating marker of inflammation in patients with BPH and PCa. C1 [Menschikowski, Mario; Hagelgans, Albert; Neumeister, Volker; Siegert, Gabriele] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Fuessel, Susanne; Wirth, Manfred P.] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Urol, D-01307 Dresden, Germany. [Mareninova, Olga A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Menschikowski, M (reprint author), Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM Mario.Menschikowski@uniklinikum-dresden.de NR 40 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 EI 1573-2576 J9 INFLAMMATION JI Inflammation PD JUN PY 2012 VL 35 IS 3 BP 1113 EP 1118 DI 10.1007/s10753-011-9418-1 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 933SI UT WOS:000303382400041 PM 22189868 ER PT J AU Tan, NX Tucker, JD AF Tan, Nicholas X. Tucker, Joseph D. TI Inequality and infection in China SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID INCOME INEQUALITY; HEALTH C1 [Tan, Nicholas X.] Harvard Univ, Fac Arts & Sci, Boston, MA 02138 USA. [Tucker, Joseph D.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Tan, NX (reprint author), Harvard Univ, Fac Arts & Sci, Boston, MA 02138 USA. EM ntan@fas.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2012 VL 16 IS 6 BP E468 EP E468 DI 10.1016/j.ijid.2012.02.008 PG 1 WC Infectious Diseases SC Infectious Diseases GA 934JN UT WOS:000303440500011 PM 22486856 ER PT J AU Premereur, E Vanduffel, W Janssen, P AF Premereur, Elsie Vanduffel, Wim Janssen, Peter TI Local Field Potential Activity Associated with Temporal Expectations in the Macaque Lateral Intraparietal Area SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSTERIOR PARIETAL CORTEX; SELECTIVE VISUAL-ATTENTION; ALPHA OSCILLATIONS; NEURONAL SYNCHRONIZATION; FREQUENCY OSCILLATIONS; HEMODYNAMIC SIGNALS; OCCIPITAL CORTEX; REPRESENTATION; MODULATION; MONKEY AB Oscillatory brain activity is attracting increasing interest in cognitive neuroscience. Numerous EEG (magnetoencephalography) and local field potential (LFP) measurements have related cognitive functions to different types of brain oscillations, but the functional significance of these rhythms remains poorly understood. Despite its proven value, LFP activity has not been extensively tested in the macaque lateral intraparietal area (LIP), which has been implicated in a wide variety of cognitive control processes. We recorded action potentials and LFPs in area LIP during delayed eye movement tasks and during a passive fixation task, in which the time schedule was fixed so that temporal expectations about task-relevant cues could be formed. LFP responses in the gamma band discriminated reliably between saccade targets and distractors inside the receptive field (RF). Alpha and beta responses were much less strongly affected by the presence of a saccade target, however, but rose sharply in the waiting period before the go signal. Surprisingly, conditions without visual stimulation of the LIP-RF-evoked robust LFP responses in every frequency band-most prominently in those below 50 Hz-precisely time-locked to the expected time of stimulus onset in the RF. These results indicate that in area LIP, oscillations in the LFP, which reflect synaptic input and local network activity, are tightly coupled to the temporal expectation of task-relevant cues. C1 [Premereur, Elsie] Katholieke Univ Leuven, Lab Neuro & Psychofysiol, B-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vanduffel, Wim] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Janssen, P (reprint author), Katholieke Univ Leuven, Lab Neuro & Psychofysiol, O&N 2,Herestr 49,Bus 1021, B-3000 Louvain, Belgium. EM Peter.Janssen@med.kuleuven.be FU Geneeskundige Stichting Koningin Elisabeth; Fonds voor Wetenschappelijk Onderzoek [G.0713.09, G.0622.08, G.0831.11]; Interuniversity Attraction Poles [P6/29]; Excellentie Financiering [EF/05/014]; National Science Foundation [BCS-0745436]; Programma Financiering [PFV/10/008]; Geconcerteerde onderzoeksacties [GOA/10/19] FX We thank Stijn Verstraeten, Piet Kayenbergh, Gerrit Meulemans, Marc De Paep, Inez Puttemans, and Marjan Docx for assistance and Steve Raiguel for comments on a previous version of this manuscript. This study was supported by Geneeskundige Stichting Koningin Elisabeth, Fonds voor Wetenschappelijk Onderzoek (G.0713.09, G.0622.08, and G.0831.11), Interuniversity Attraction Poles (P6/29), Excellentie Financiering (EF/05/014), National Science Foundation (BCS-0745436), Programma Financiering (PFV/10/008), and Geconcerteerde onderzoeksacties (GOA/10/19). NR 53 TC 6 Z9 6 U1 0 U2 11 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUN PY 2012 VL 24 IS 6 BP 1314 EP 1330 PG 17 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 935EK UT WOS:000303501600005 PM 22390466 ER PT J AU So, K Ganguly, K Jimenez, J Gastpar, MC Carmena, JM AF So, Kelvin Ganguly, Karunesh Jimenez, Jessica Gastpar, Michael C. Carmena, Jose M. TI Redundant information encoding in primary motor cortex during natural and prosthetic motor control SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Mutual information; Neural ensemble; Motor control; Brain-machine interface; Electrophysiology; Primary motor cortex ID CORTICAL-NEURONS; POPULATION CODES; MOVEMENT DIRECTION; ARM MOVEMENTS; DISCHARGE; SYNERGY; REORGANIZATION; INDEPENDENCE; INTERFACE AB Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control. C1 [So, Kelvin; Jimenez, Jessica; Gastpar, Michael C.; Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, San Francisco, CA USA. [Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Gastpar, Michael C.] Ecole Polytech Fed Lausanne, Sch Comp & Commun Sci, EPFL, Lausanne, Switzerland. [Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, UCB UCSF Joint Grad Grp Bioengn, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA. RP Carmena, JM (reprint author), Univ Calif Berkeley, Dept Elect Engn & Comp Sci, 754 Sutardja Dai Hall, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu FU National Science Foundation CDI; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development; American Heart Association/American Stroke Association FX The research reported here was supported by the National Science Foundation CDI Type-I grant to M.C.G. and J.M.C., and the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development, and the American Heart Association/American Stroke Association to K.G. NR 26 TC 4 Z9 4 U1 2 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD JUN PY 2012 VL 32 IS 3 BP 555 EP 561 DI 10.1007/s10827-011-0369-1 PG 7 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 936KO UT WOS:000303589500011 PM 22042443 ER PT J AU Tolboom, H Izamis, ML Sharma, N Milwid, JM Uygun, B Berthiaume, F Uygun, K Yarmush, ML AF Tolboom, Herman Izamis, Maria-Louisa Sharma, Nripen Milwid, Jack M. Uygun, Basak Berthiaume, Francois Uygun, Korkut Yarmush, Martin L. TI Subnormothermic Machine Perfusion at Both 20 degrees C and 30 degrees C Recovers Ischemic Rat Livers for Successful Transplantation SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE liver transplantation; reperfusion injury; sub-normothermic machine perfusion ID NORMOTHERMIC EXTRACORPOREAL PERFUSION; HEART-BEATING DONOR; ORGAN-PRESERVATION; REPERFUSION INJURY; STEATOTIC LIVERS; TEMPERATURE; GRAFTS; FUTURE; MODEL AB Background. Utilizing livers from donors after cardiac death could significantly expand the donor pool. We have previously shown that normothermic (37 degrees C) extracorporeal liver perfusion significantly improves transplantation outcomes of ischemic rat livers. Here we investigate whether recovery of ischemic livers is possible using sub-normothermic machine perfusion at 20 degrees C and 30 degrees C. Methods. Livers from male Lewis rats were divided into five groups after 1 h of warm ischemia (WI): (1) WI only, (2) 5 h of static cold storage (SCS), or 5 h of MP at (3) 20 degrees C, (4) 30 degrees C, and (5) 37 degrees C. Long-term graft performance was evaluated for 28 d post-transplantation. Acute graft performance was evaluated during a 2 h normothermic sanguineous reperfusion ex vivo. Fresh livers with 5 h of SCS were positive transplant controls while fresh livers were positive reperfusion controls. Results. Following machine perfusion (MP) (Groups 3, 4, and 5), ischemically damaged livers could be ortho-topically transplanted into syngeneic recipients with 100% survival (N >= 4) after 4 wk. On the other hand, animals from WI only, or WI + SCS groups all died within 24 h of transplantation. Fresh livers preserved using SCS had the highest alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the lowest bile production during reperfusion, while at 28 d post-transplantation, livers preserved at 20 degrees C and 30 degrees C had the highest total bilirubin values. Conclusions. MP at both 20 degrees C and 30 degrees C eliminated temperature control in perfusion systems and recovered ischemically damaged rat livers. Postoperatively, low transaminases suggest a beneficial effect of sub-normothermic perfusion, while rising total bilirubin levels suggest inadequate prevention of ischemia-or hypothermia-induced biliary damage. (C) 2012 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Ctr Engn Med, Boston, MA USA. Shriners Burns Hosp, Boston, MA USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Uygun, Basak/I-1792-2012 OI Uygun, Basak/0000-0002-2600-7900 FU National Institutes of Health [R01DK59766, R00DK080942]; Shriners Hospitals for Children FX This work was supported by grants from the National Institutes of Health (R01DK59766, R00DK080942) and the Shriners Hospitals for Children. NR 36 TC 30 Z9 34 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN 1 PY 2012 VL 175 IS 1 BP 149 EP 156 DI 10.1016/j.jss.2011.03.003 PG 8 WC Surgery SC Surgery GA 934UP UT WOS:000303472500029 PM 21550058 ER PT J AU Garrido, MM Allison, KC Bergeron, MJ Dowd, B AF Garrido, Melissa M. Allison, Kirk C. Bergeron, Mark J. Dowd, Bryan TI Hospital Religious Affiliation and Outcomes for High-Risk Infants SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE infant mortality; hospital ownership; religious affiliation ID BIRTH-WEIGHT INFANTS; OF-LIFE; EMERGENCY CONTRACEPTION; MORTALITY-RATES; INTENSIVE-CARE; NEONATAL CARE; UNITED-STATES; SERVICES; END; PROVISION AB The effect of hospital organizational affiliation on perinatal outcomes is unknown. Using the 2004 American Hospital Association Annual Survey and Healthcare Cost and Utilization Project State Inpatient Databases, the authors examined relationships among organizational affiliation, equipment and service availability and provision, and in-hospital mortality for 5,133 infants across five states born with very low and extremely low birth weight and congenital anomalies. In adjusted bivariate probit selection models, the authors found that government hospitals had significantly higher mortality rates than not-for-profit nonreligious hospitals. Mortality differences among other types of affiliation (Catholic, not-for-profit religious, not-for-profit nonreligious, and for-profit) were not statistically significant. This is encouraging as health care reform efforts call for providers at facilities with different institutional values to coordinate care across facilities. Although there are anecdotes of facility religious affiliation being related to health care decisions, the authors did not find evidence of these relationships in their data. C1 [Garrido, Melissa M.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Garrido, Melissa M.] Mt Sinai Sch Med, New York, NY USA. [Allison, Kirk C.; Dowd, Bryan] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Bergeron, Mark J.] Univ Minnesota, Sch Med, St Paul, MN 55108 USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu OI Garrido, Melissa/0000-0002-8986-3536 FU Wessner Foundation; MacLaurinCSF FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This grant was supported in part by funding to Dr. Dowd from the Wessner Foundation and MacLaurinCSF. NR 52 TC 1 Z9 1 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD JUN PY 2012 VL 69 IS 3 BP 316 EP 338 DI 10.1177/1077558711432156 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 933YB UT WOS:000303401900004 PM 22203647 ER PT J AU Kahn, JM Werner, RM Carson, SS Iwashyna, TJ AF Kahn, Jeremy M. Werner, Rachel M. Carson, Shannon S. Iwashyna, Theodore J. TI Variation in Long-Term Acute Care Hospital Use After Intensive Care SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE mechanical ventilation; intensive care; long-term acute care; post-acute care utilization; practice variation ID PROLONGED MECHANICAL VENTILATION; MEDICARE; OUTCOMES; ILLNESS; TRIAL; UNITS AB Long-term acute care hospitals (LTACs) are an increasingly common discharge destination for patients recovering from intensive care. In this article the authors use U.S. Medicare claims data to examine regional- and hospital-level variation in LTAC utilization after intensive care to determine factors associated with their use. Using hierarchical regression models to control for patient characteristics, this study found wide variation in LTAC utilization across hospitals, even controlling for LTAC access within a region. Several hospital characteristics were independently associated with increasing LTAC utilization, including increasing hospital size, for-profit ownership, academic teaching status, and colocation of the LTAC within an acute care hospital. These findings highlight the need for research into LTAC admission criteria and the incentives driving variation in LTAC utilization across hospitals. C1 [Kahn, Jeremy M.] Univ Pittsburgh, Dept Crit Med, Sch Med, Pittsburgh, PA 15261 USA. [Kahn, Jeremy M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Carson, Shannon S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Iwashyna, Theodore J.] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Kahn, JM (reprint author), Univ Pittsburgh, Dept Crit Med, Sch Med, Scaife Hall,Room 602-B,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kahnjm@upmc.edu OI Iwashyna, Theodore/0000-0002-4226-9310 FU United States National Institutes of Health [R01HL096651] FX This work was funded by the United States National Institutes of Health (R01HL096651). NR 20 TC 17 Z9 18 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD JUN PY 2012 VL 69 IS 3 BP 339 EP 350 DI 10.1177/1077558711432889 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 933YB UT WOS:000303401900005 PM 22311957 ER PT J AU Oh, B Butow, PN Mullan, BA Clarke, SJ Beale, PJ Pavlakis, N Lee, MS Rosenthal, DS Larkey, L Vardy, J AF Oh, Byeongsang Butow, Phyllis N. Mullan, Barbara A. Clarke, Stephen J. Beale, Philip J. Pavlakis, Nick Lee, Myeong Soo Rosenthal, David S. Larkey, Linda Vardy, Janette TI Effect of medical Qigong on cognitive function, quality of life, and a biomarker of inflammation in cancer patients: a randomized controlled trial SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Cancer; Cognitive function; Quality of life; Inflammation; Medical Qigong ID STANDARD-DOSE CHEMOTHERAPY; C-REACTIVE PROTEIN; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; WOMEN; SURVIVORS; THERAPY; IMPAIRMENT; SYMPTOMS; PERFORMANCE AB Cancer patients often experience diminished cognitive function (CF) and quality of life (QOL) due to the side effects of treatment and the disease symptoms. This study evaluates the effects of medical Qigong (MQ; combination of gentle exercise and meditation) on CF, QOL, and inflammation in cancer patients. Eighty-one cancer patients recruited between October 2007 and May 2008 were randomly assigned to two groups: a control group (n = 44) who received the usual health care and an intervention group (n = 37) who participated in a 10-week MQ program. Self-reported CF was measured by the European Organization for Research and Treatment of Cancer (EORTC-CF) and the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog). The Functional Assessment of Cancer Therapy-General (FACT-G) was used to measure QOL. C-reactive protein (CRP) was assessed as a biomarker of inflammation. The MQ group self-reported significantly improved CF (mean difference (MD) = 7.78, t (51) = -2.532, p = 0.014) in the EORTC-CF and all the FACT-Cog subscales [perceived cognitive impairment (MD = 4.70, t (43) = -2.254, p = 0.029), impact of perceived cognitive impairment on QOL (MD = 1.64, t (45) = -2.377, p = 0.024), and perceived cognitive abilities (MD = 3.61, t (45) = -2.229, p = 0.031)] compared to controls. The MQ group also reported significantly improved QOL (MD = 12.66, t (45) = -5.715, p < 0.001) and had reduced CRP levels (MD = -0.72, t (45) = 2.092, p = 0.042) compared to controls. Results suggest that MQ benefits cancer patients' self-reported CF, QOL, and inflammation. A larger randomized controlled trial including an objective assessment of CF is planned. C1 [Oh, Byeongsang; Clarke, Stephen J.; Beale, Philip J.; Pavlakis, Nick] Royal N Shore Hosp, Dept Med Oncol, St Leonards, NSW 2065, Australia. [Lee, Myeong Soo] Korea Inst Oriental Med, Brain Dis Res Ctr, Taejon 305811, South Korea. [Rosenthal, David S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Larkey, Linda] Arizona State Univ, Scottsdale Healthcare Chair Biobehav Oncol Res, Coll Nursing & Hlth Innovat, Tempe, AZ USA. [Oh, Byeongsang; Clarke, Stephen J.; Beale, Philip J.; Vardy, Janette] Univ Sydney, Sydney Med Sch, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. [Oh, Byeongsang; Clarke, Stephen J.; Beale, Philip J.; Vardy, Janette] Concord Repatriat Gen Hosp, Sydney, NSW, Australia. [Oh, Byeongsang; Butow, Phyllis N.; Mullan, Barbara A.; Vardy, Janette] Univ Sydney, Ctr Med Psychol & Evidence Based Decisionmaking C, Sch Psychol, Sydney, NSW 2006, Australia. RP Oh, B (reprint author), Royal N Shore Hosp, Dept Med Oncol, St Leonards, NSW 2065, Australia. EM byeong.oh@sydney.edu.au; phyllisb@psych.usyd.edu.au; barbara@psych.usyd.edu.au; stephen.clarke@sydney.edu.au; Philip.Beale@sswahs.nsw.gov.au; nick.pavlakis@sydney.edu.au; drmslee@gmail.com; drose@uhs.harvard.edu; linda.larkey@asu.edu; janette.vardy@sydney.edu.au RI Lee, Myeong Soo/C-8147-2013; OI Lee, Myeong Soo/0000-0001-6651-7641; Mullan, Barbara/0000-0002-0177-8899; Vardy, Janette/0000-0002-5739-5790 FU University of Sydney; Royal Prince Alfred Hospital, Concord Hospital; Royal North Shore Hospital FX This study was supported by the University of Sydney Cancer Research Fund. The authors would like to thank the support provided for the study by the medical oncologists of Royal Prince Alfred Hospital, Concord Hospital and Royal North Shore Hospital. The authors wish to acknowledge the contribution of the biostatistician, Prof. Judy Simpson, who provided statistical assistance and especially to thank the participants who made this study possible. NR 40 TC 58 Z9 60 U1 2 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JUN PY 2012 VL 20 IS 6 BP 1235 EP 1242 DI 10.1007/s00520-011-1209-6 PG 8 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 935PN UT WOS:000303532000015 PM 21688163 ER PT J AU Tezil, T Bodur, C Kutuk, O Basaga, H AF Tezil, Tugsan Bodur, Cagri Kutuk, Ozgur Basaga, Huveyda TI IKK-beta mediates chemoresistance by sequestering FOXO3; A critical factor for cell survival and death SO CELLULAR SIGNALLING LA English DT Article DE FOXO3; IKK; Chemoresistance; Cell death; Breast cancer ID TRANSCRIPTION FACTOR FOXO3A; BREAST-CANCER CELLS; RECEPTOR-ALPHA EXPRESSION; CISPLATIN RESISTANCE; PROMOTES TUMORIGENESIS; KINASE INHIBITOR; GEFITINIB IRESSA; GENE-EXPRESSION; P53 MUTANTS; APOPTOSIS AB Chemotherapeutic drugs proved only 50% successful in breast cancer because of cell type-dependent resistance mechanisms. FOXO3 is known to be involved in the regulation of several cell death-related genes; however, the extent of FOXO3 regulation in chemoresistance is still not fully understood. Here, we show that FOXO3 critically mediates cisplatin chemosensitivity of MCF-7 breast cancer cells which express higher levels of FOXO3 compared to resistant MDA-MB-231 cells. Administration of cisplatin induces apoptosis in MCF-7 cells in a FOXO3-dependent manner as indicated by RNA interference. On the other hand, IKK-beta (I kappa B kinase) appears to inhibit FOXO3 action after cisplatin treatment and promotes chemoresistance in MDA-MB-231 cells. IKK-p directly interacts and sequesters FOXO3 in the cytosol preventing its nuclear localization. Moreover, cisplatin treatment induces autophagosome formation through LC-3 conversion while inhibiting the cleavage of caspase 9 and caspase 3 in MDA-MB-231 cells manipulated to overexpress FOXO3. In brief, our findings demonstrate that in addition to cellular level of active FOXO3, cisplatin chemoresistance is also regulated by IKK-beta sequestration of FOXO3 in cytosol. (C) 2012 Elsevier Inc. All rights reserved. C1 [Tezil, Tugsan; Bodur, Cagri; Basaga, Huveyda] Sabanci Univ, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey. [Kutuk, Ozgur] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Basaga, H (reprint author), Sabanci Univ, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey. EM teziltugsan@su.sabanciuniv.edu; bodur@sabanciuniv.edu; ozgur_kutuk@dfci.harvard.edu; huveyda@sabanciuniv.edu RI Tezil, Tugsan/A-3909-2013 OI Tezil, Tugsan/0000-0003-0796-3718 FU TUBITAK [109S340]; Turkish Association for Cancer Research and Control; Yousef Jameel Scholarship FX We thank GJ Gores (Mayo Clinic, Minnesota) for pELE-HA-FOXO3(wt) plasmid, MC Hung (MD Anderson Cancer Center, Texas) for pEGFP-FOXO3(S644A) plasmid, RB Gaynor (Harold Simmons Cancer Center, Texas) for pCMV-flag-IKK-beta plasmid and D Gozuacik (Sabanci University, Turkey) for pEGFP-LC3 plasmid. This work was supported by the grants from TUBITAK (SBAG#109S340) (HB), and Turkish Association for Cancer Research and Control-Terry Fox Cancer Research Fund (TT). TT is supported by Yousef Jameel Scholarship. NR 46 TC 9 Z9 10 U1 0 U2 6 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 2012 VL 24 IS 6 BP 1361 EP 1368 DI 10.1016/j.cellsig.2012.01.012 PG 8 WC Cell Biology SC Cell Biology GA 929WU UT WOS:000303097200028 PM 22313691 ER PT J AU Bartzokis, G AF Bartzokis, George TI Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments SO NEUROPHARMACOLOGY LA English DT Review DE White matter; Oligodendrocyte; Intracortical myelin; Medication; MRI; NG2 cells; Neuregulin; ErbB; DISC1; IGF1; Reelin; Cdk; MAPK; mTOR; Leptin ID GROWTH-FACTOR-I; CENTRAL-NERVOUS-SYSTEM; GLYCOGEN-SYNTHASE KINASE-3; WHITE-MATTER ABNORMALITIES; ACTIVATED PROTEIN-KINASE; NICOTINIC ACETYLCHOLINE-RECEPTOR; OLIGODENDROCYTE PROGENITOR CELLS; DORSOLATERAL PREFRONTAL CORTEX; SEIZURES INDUCE PROLIFERATION; NG2-EXPRESSING GLIAL-CELLS AB Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. Published by Elsevier Ltd. C1 [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Lab Neuroimaging,Dept Neurol, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU Pfizer; Janssen; Novartis; NIH [MH066029, AG027342]; Research and Psychiatry Services of the Department of Veterans Affairs; RCS Foundation FX George Bartzokis has consulted for and received research funding from Pfizer, Janssen, and Novartis, and consulted for Bristol-Myers Squibb Company.; This work was supported in part by NIH grants (MH066029; AG027342), Research and Psychiatry Services of the Department of Veterans Affairs, and the RCS Foundation. The author thanks Lori L Altshuler, M.D., and Keith H. Nuechterlein, Ph.D. for reading the manuscript and providing helpful suggestions. NR 271 TC 46 Z9 47 U1 2 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2012 VL 62 IS 7 BP 2137 EP 2153 DI 10.1016/j.neuropharm.2012.01.015 PG 17 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 931MG UT WOS:000303223400001 PM 22306524 ER PT J AU Shabani, S Dobbs, LK Ford, MM Mark, GP Finn, DA Phillips, TJ AF Shabani, Shkelzen Dobbs, Lauren K. Ford, Matthew M. Mark, Gregory P. Finn, Deborah A. Phillips, Tamara J. TI A genetic animal model of differential sensitivity to methamphetamine reinforcement SO NEUROPHARMACOLOGY LA English DT Article DE Methamphetamine; Addiction; Oral self-administration; Reinforcement; Appetitive; Aversive ID RECOMBINANT INBRED MICE; C57BL/6J MICE; D-AMPHETAMINE; BEHAVIORAL SENSITIZATION; ETHANOL SEEKING; NATURAL REWARDS; DRUG; RATS; ALCOHOL; COCAINE AB Sensitivity to reinforcement from methamphetamine (MA) likely influences risk for MA addiction, and genetic differences are one source of individual variation. Generation of two sets of selectively bred mouse lines for high and low MA drinking has shown that genetic factors influence MA intake, and pronounced differences in sensitivity to rewarding and aversive effects of MA play a significant role. Further validation of these lines as a unique genetic model relevant to MA addiction was obtained using operant methods to study MA reinforcement High and low MA drinking line mice were used to test the hypotheses that: 1) oral and intracerebroventricular (ICV) MA serve as behavioral reinforcers, and 2) MA exhibits greater reinforcing efficacy in high than low MA drinking mice. Operant responses resulted in access to an MA or non-MA drinking tube or intracranial delivery of MA. Behavioral activation consequent to orally consumed MA was determined. MA available for consumption maintained higher levels of reinforced instrumental responding in high than low MA drinking line mice, and MA intake in the oral operant procedure was greater in high than low MA drinking line mice. Behavioral activation was associated with amount of MA consumed during operant sessions. High line mice delivered more MA via ICV infusion than did low line mice across a range of doses. Thus, genetic risk factors play a critical role in the reinforcing efficacy of MA and the oral self-administration procedure is suitable for delineating genetic contributions to MA reinforcement. Published by Elsevier Ltd. C1 [Shabani, Shkelzen; Dobbs, Lauren K.; Ford, Matthew M.; Mark, Gregory P.; Finn, Deborah A.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Shabani, Shkelzen; Dobbs, Lauren K.; Ford, Matthew M.; Mark, Gregory P.; Finn, Deborah A.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. [Finn, Deborah A.; Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Phillips, TJ (reprint author), Portland VA Med Ctr VAMC, R&D 32,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM shabanis@scripps.edu; dobbsl@ohsu.edu; fordma@ohsu.edu; markg@ohsu.edu; finnd@ohsu.edu; phillipt@ohsu.edu OI Ford, Matthew/0000-0002-1204-1980 FU Department of Veterans Affairs; NIDA [T32 DA07262]; NIDA Center [P50 DA018165]; NIAAA [K01 AA016849] FX We thank Andrew Fredericks and Becca Rieger for their help collecting oral operant self-administration data. We also thank Tammie Painter, Marcia Ramaker and Nathan Klett for their help with ICV data collection. This work was supported by the Department of Veterans Affairs, NIDA T32 DA07262, and NIDA Center grant P50 DA018165. In addition, NIAAA K01 AA016849 provided some salary support. The oral operant self-administration and locomotor activity studies were in part supported with resources and the use of facilities at the Portland VA Medical Center. NR 54 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2012 VL 62 IS 7 BP 2169 EP 2177 DI 10.1016/j.neuropharm.2012.01.002 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 931MG UT WOS:000303223400003 PM 22280875 ER PT J AU Cotter, SE McBride, SM Yock, TI AF Cotter, Shane E. McBride, Sean M. Yock, Torunn I. TI Proton Radiotherapy for Solid Tumors of Childhood SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE Protons; Radiation therapy; Pediatric cancer ID CHILDRENS CANCER GROUP; GERM-CELL TUMORS; MODULATED RADIATION-THERAPY; PRIOR CRANIAL IRRADIATION; PEDIATRIC BRAIN-TUMORS; CENTRAL-NERVOUS-SYSTEM; LONG-TERM SURVIVORS; INDUCED 2ND CANCERS; LOW-GRADE GLIOMAS; PHASE-II TRIAL AB The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. C1 [Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Cotter, Shane E.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Cotter, Shane E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McBride, Sean M.] Harvard Radiat Oncol Program, Boston, MA 02115 USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM tyock@partners.org NR 100 TC 7 Z9 7 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-0346 EI 1533-0338 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD JUN PY 2012 VL 11 IS 3 BP 267 EP 278 DI 10.7785/tcrt.2012.500295 PG 12 WC Oncology SC Oncology GA 926JK UT WOS:000302827000008 PM 22417062 ER PT J AU Pedamallu, CS Ozdamar, L Kropat, E Weber, GW AF Pedamallu, Chandra Sekhar Ozdamar, Linet Kropat, Erik Weber, Gerhard-Wilhelm TI A system dynamics model for intentional transmission of HIV/AIDS using cross impact analysis SO CENTRAL EUROPEAN JOURNAL OF OPERATIONS RESEARCH LA English DT Article DE HIV transmission by non-disclosure; Cross impact analysis; System dynamics ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED-DISEASES; SOUTH-AFRICA; HIV; SIMULATION; FUTURE; AIDS; INTERSECTIONS; PREVENTION; DISCLOSURE AB The system dynamics approach is a holistic way of solving problems in real-time scenarios. This is a powerful methodology and computer simulation modeling technique for framing, understanding, and discussing complex issues and problems. System dynamics modeling and simulation is often the background of a systemic thinking approach and has become a management and organizational development paradigm. This paper proposes a system dynamics approach for modeling the phenomenon of intentional transmission of HIV/AIDS by non-disclosure. The model is built using the Cross Impact Analysis (CIA) method of relating entities and attributes relevant to the risky conduct of HIV+ individuals in any given community. The proposed model uses a hypothetical cross impact matrix that relates pairs of attributes. The factors that impact non-disclosure are identified by simulating the model through dynamic difference equations. After the simulation results are reviewed, two policies are introduced and tested in order to observe the progress in the system state. C1 [Weber, Gerhard-Wilhelm] Middle E Tech Univ, Dept Financial Math, Inst Appl Math, TR-06531 Ankara, Turkey. [Weber, Gerhard-Wilhelm] Middle E Tech Univ, Dept Actuarial Sci, Inst Appl Math, TR-06531 Ankara, Turkey. [Weber, Gerhard-Wilhelm] Middle E Tech Univ, Dept Comp Sci, Inst Appl Math, TR-06531 Ankara, Turkey. [Pedamallu, Chandra Sekhar] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pedamallu, Chandra Sekhar] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ozdamar, Linet] Yeditepe Univ, Dept Syst Engn, TR-34755 Istanbul, Turkey. [Kropat, Erik] Univ Bundeswehr Munchen, Dept Informat, Inst Theoret Comp Sci Math & Operat Res, D-85577 Neubiberg, Germany. [Weber, Gerhard-Wilhelm] Univ Siegen, Fac Econ Business & Law, Siegen, Germany. [Weber, Gerhard-Wilhelm] Univ Aveiro, Ctr Res Optimizat & Control, P-3800 Aveiro, Portugal. [Weber, Gerhard-Wilhelm] Univ Teknol Malaysia, Skudai, Malaysia. RP Weber, GW (reprint author), Middle E Tech Univ, Dept Financial Math, Inst Appl Math, TR-06531 Ankara, Turkey. EM pcs.murali@gmail.com; ozdamar.linet@gmail.com; kropat@am.uni-erlangen.de; gweber@metu.edu.tr NR 48 TC 3 Z9 3 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1435-246X EI 1613-9178 J9 CENT EUR J OPER RES JI Cent. Europ. J. Oper. Res. PD JUN PY 2012 VL 20 IS 2 BP 319 EP 336 DI 10.1007/s10100-010-0183-2 PG 18 WC Operations Research & Management Science SC Operations Research & Management Science GA 921KU UT WOS:000302477300006 ER PT J AU Forman, EM Chapman, JE Herbert, JD Goetter, EM Yuen, EK Moitra, E AF Forman, Evan M. Chapman, Jason E. Herbert, James D. Goetter, Elizabeth M. Yuen, Erica K. Moitra, Ethan TI Using Session-by-Session Measurement to Compare Mechanisms of Action for Acceptance and Commitment Therapy and Cognitive Therapy SO BEHAVIOR THERAPY LA English DT Article DE ACT; CBT; psychotherapy mechanisms; mediation ID BEHAVIORAL TREATMENT; CONFIDENCE-LIMITS; CONTROLLED TRIAL; DEPRESSION; ANXIETY; MEDIATION; PREVENT; RELAPSE; QUESTIONNAIRE; RELIABILITY AB Debate continues about the extent to which postulated mechanisms of action of cognitive behavior therapies (CBT), including standard CBT (i.e., Beckian cognitive therapy [CT]) and acceptance and commitment therapy (ACT) are supported by mediational analyses. Moreover, the distinctiveness of CT and ACT has been called into question. One contributor to ongoing uncertainty in this arena is the lack of time-varying process data. In this study, 174 patients presenting to a university clinic with anxiety or depression who had been randomly assigned to receive either ACT or CT completed an assessment of theorized mediators and outcomes before each session. Hierarchical linear modeling of session-by-session data revealed that increased utilization of cognitive and affective change strategies relative to utilization of psychological acceptance strategies mediated outcome for CT, whereas for ACT the mediation effect was in the opposite direction. Decreases in self-reported dysfunctional thinking, cognitive "defusion" (the ability to see one's thoughts as mental events rather than necessarily as representations of reality), and willingness to engage in behavioral activity despite unpleasant thoughts or emotions were equivalent mediators across treatments. These results have potential implications for the theoretical arguments behind, and distinctiveness of, CT and ACT. C1 [Forman, Evan M.] Drexel Univ, Dept Psychol, Philadelphia, PA 19102 USA. [Yuen, Erica K.] Med Univ S Carolina, Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Moitra, Ethan] Brown Univ, Providence, RI 02912 USA. RP Forman, EM (reprint author), Drexel Univ, Dept Psychol, 245 N 15th St,MS 626, Philadelphia, PA 19102 USA. EM evan.forman@drexel.edu RI Forman, Evan/I-1042-2012 NR 61 TC 35 Z9 35 U1 7 U2 43 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2012 VL 43 IS 2 BP 341 EP 354 PG 14 WC Psychology, Clinical SC Psychology GA 920GZ UT WOS:000302393600010 PM 22440070 ER PT J AU Gray, MJ Schorr, Y Nash, W Lebowitz, L Amidon, A Lansing, A Maglione, M Lang, AJ Litz, BT AF Gray, Matt J. Schorr, Yonit Nash, William Lebowitz, Leslie Amidon, Amy Lansing, Amy Maglione, Melissa Lang, Ariel J. Litz, Brett T. TI Adaptive Disclosure: An Open Trial of a Novel Exposure-Based Intervention for Service Members With Combat-Related Psychological Stress Injuries SO BEHAVIOR THERAPY LA English DT Article DE Combat; trauma; psychotherapy; moral injury; PTSD ID MENTAL-HEALTH PROBLEMS; PSYCHOMETRIC PROPERTIES; PTSD CHECKLIST; DISORDER; VETERANS; IRAQ; AFGHANISTAN; THERAPY; PSYCHOTHERAPY; VALIDATION AB We evaluated the preliminary effectiveness of a novel intervention that was developed to address combat stress injuries in active-duty military personnel. Adaptive disclosure (AD) is relatively brief to accommodate the busy schedules of active-duty service members while training for future deployments. Further, AD takes into account unique aspects of the phenomenology of military service in war in order to address difficulties such as moral injury and traumatic loss that may not receive adequate and explicit attention by conventional treatments that primarily address fear-inducing life-threatening experiences and sequelae. In this program development and evaluation open trial, 44 marines received AD while in garrison. It was well tolerated and, despite the brief treatment duration, promoted significant reductions in PTSD, depression, negative posttraumatic appraisals, and was also associated with increases in posttraumatic growth. C1 [Gray, Matt J.] Univ Wyoming, Dept Psychol, Dept 3415, Laramie, WY 82070 USA. [Schorr, Yonit; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Nash, William] Def Ctr Excellence, Arlington, VA USA. [Amidon, Amy; Lansing, Amy; Maglione, Melissa; Lang, Ariel J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Amidon, Amy; Lansing, Amy; Maglione, Melissa; Lang, Ariel J.] VA San Diego Healthcare Syst, San Diego, CA USA. [Litz, Brett T.] Boston Univ, Boston, MA 02215 USA. [Litz, Brett T.] Massachusetts Vet Epidemiol Res & Informat Ctr, Natl Ctr PTSD, Bedford, MA USA. RP Gray, MJ (reprint author), Univ Wyoming, Dept Psychol, Dept 3415, 1000 E Univ Ave, Laramie, WY 82070 USA. EM gray@uwyo.edu NR 26 TC 30 Z9 30 U1 0 U2 16 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD JUN PY 2012 VL 43 IS 2 BP 407 EP 415 PG 9 WC Psychology, Clinical SC Psychology GA 920GZ UT WOS:000302393600015 PM 22440075 ER PT J AU Cohen, LE Gordon, JH Popovsky, EY Sainath, NN Feldman, HA Kieran, MW Gordon, CM AF Cohen, Laurie E. Gordon, Joshua H. Popovsky, Erica Y. Sainath, Nina N. Feldman, Henry A. Kieran, Mark W. Gordon, Catherine M. TI Bone density in post-pubertal adolescent survivors of childhood brain tumors SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bone mineral density; brain tumors; growth hormone deficiency; fracture ID ACUTE LYMPHOBLASTIC-LEUKEMIA; YOUNG-ADULT SURVIVORS; QUALITY-OF-LIFE; MINERAL DENSITY; GROWTH-HORMONE; PHYSICAL-ACTIVITY; RADIATION-THERAPY; CANCER; CHILDREN; MASS AB Background Childhood cancer survivors are at high risk for reduced bone mineral density (BMD). Our objective was to determine whether post-pubertal adolescent survivors of brain tumors, whose tumor or treatments placed them at risk for pituitary hormone deficiencies, have low BMD near time of peak bone mass accrual, and to assess risk factors for decreased BMD. Procedure. Chart review of 36 post-pubertal adolescents with history of tumor or radiation therapy (RT) of the hypothalamicpituitary area who had undergone BMD screening via dual-energy X-ray absorptiometry (DXA). Results. Age at DXA was 16.9 +/- 1.9 years (mean +/- SD). Time since diagnosis was 8.5 +/- 3.6 years. Median BMD Z scores were -0.95 (range -2.7 to 1.7) at the femoral neck, -1.20 (-3.6 to 1.8) at the hip, and -0.90 (-3.7 to 1.8) at the spine. Bone mineral apparent density (BMAD) Z scores were -0.23 (-2.7 to 1.9) at the femoral neck and -0.45 (-3.0 to 2.3) at the spine. Those with history of >= 1 fracture had lower BMD Z scores of the femoral neck, total hip, and spine (P < 0.05). Those with treated GH deficiency (GHD) had a higher BMD Z-score at the femoral neck, total hip, and spine (P < 0.05) than those not treated. There was no difference in BMD with respect to treatment with chemotherapy, cranial or spinal RT, or hypogonadism. Spontaneous menarche and regular periods did not correlate with BMD. Conclusions. In post-pubertal adolescent survivors of childhood brain tumors, fracture history and untreated GHD are risk factors for decreased BMD. Pediatr Blood Cancer 2012; 58: 959-963. (C) 2011 Wiley Periodicals, Inc. C1 [Cohen, Laurie E.; Gordon, Joshua H.; Popovsky, Erica Y.; Gordon, Catherine M.] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. [Sainath, Nina N.] NYU, Sch Med, New York, NY USA. [Feldman, Henry A.] Childrens Hosp Boston, Clin Res Program, Boston, MA 02115 USA. [Kieran, Mark W.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cohen, LE (reprint author), Childrens Hosp Boston, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. EM laurie.cohen@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Harvard Clinical and Translational Science Center [NIH UL1 RR-025758] FX Grant sponsor: Harvard Clinical and Translational Science Center; Grant number: NIH UL1 RR-025758. NR 41 TC 2 Z9 2 U1 0 U2 2 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2012 VL 58 IS 6 BP 959 EP 963 DI 10.1002/pbc.23300 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 910QQ UT WOS:000301656300024 PM 22431246 ER PT J AU Bymaster, FP Golembiowska, K Kowalska, M Choi, YK Tarazi, FI AF Bymaster, Frank P. Golembiowska, Krystyna Kowalska, Magdalena Choi, Yong Kee Tarazi, Frank I. TI Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: Implications for treatment of attention-deficit hyperactivity disorder SO SYNAPSE LA English DT Article DE norepinephrine transporter; dopamine transporter; ADHD; microdialysis; locomotor activity ID ADJUNCT OROS-METHYLPHENIDATE; RAT PREFRONTAL CORTEX; DEFICIT/HYPERACTIVITY DISORDER; EXTRACELLULAR DOPAMINE; MOTOR HYPERACTIVITY; SEROTONIN UPTAKE; ATOMOXETINE; ADULTS; ADHD; BRAIN AB We report on the pharmacological, behavioral, and neurochemical characterization of a novel dual norepinephrine (NE)/dopamine (DA) transporter inhibitor EB-1020 (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane HCl). EB-1020 preferentially inhibited monoamine reuptake in cloned cell lines transfected with human transporters with IC50 values of 6 and 38, respectively, for NE and DA transporters. In microdialysis studies, EB-1020 markedly increased NE, and DA concentrations levels in rat prefrontal cortex in vivo with peak increases of 375 and 300%, respectively with the greatest effects on NE, and also increased DA extracellular concentrations in the striatum to 400% of baseline concentrations. Behavioral studies demonstrated that EB-1020 dose-dependently decreased immobility in the mouse tail suspension test of depression to 13% of control levels, and did not stimulate locomotor activity in adult rats in the optimal dose range. EB-1020 dose-dependently inhibited locomotor hyperactivity in juvenile rats lesioned with the neurotoxin 6-hydroxydopamine (100 mu g intracisternally) as neonates; a well-established animal model for attention-deficit hyperactivity disorder (ADHD). These data suggest that EB-1020 mediates its actions by stimulating NE and DA neurotransmission, which are typically impaired in ADHD. Synapse, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Bymaster, Frank P.] Euthym Biosci Inc, Cambridge, MA 02141 USA. [Golembiowska, Krystyna; Kowalska, Magdalena] Polish Acad Sci, Inst Pharmacol, Dept Pharmacol, PL-31343 Krakow, Poland. [Choi, Yong Kee; Tarazi, Frank I.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. [Choi, Yong Kee; Tarazi, Frank I.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02478 USA. [Choi, Yong Kee; Tarazi, Frank I.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02478 USA. RP Tarazi, FI (reprint author), Euthym Biosci Inc, 43 Thorndike St,Suite 1-3, Cambridge, MA 02141 USA. EM fbymaster@euthymics.com FU Euthymics Biosciences FX Frank P. Bymaster is an employee, officer, and shareholder in Euthymics Biosciences Inc. Drs. Krystyna Golembiowska and Frank Tarazi received funding from Euthymics Biosciences to conduct the microdialysis studies and ADHD model studies respectively. NR 63 TC 8 Z9 8 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 2012 VL 66 IS 6 BP 522 EP 532 DI 10.1002/syn.21538 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 919AP UT WOS:000302293300006 PM 22298359 ER PT J AU Fisher, MC Furer, V Hochberg, MC Greenberg, JD Kremer, JM Curtis, JR Reed, G Harrold, L Solomon, DH AF Fisher, Mark C. Furer, Victoria Hochberg, Marc C. Greenberg, Jeffrey D. Kremer, Joel M. Curtis, Jeff R. Reed, George Harrold, Leslie Solomon, Daniel H. TI Malignancy validation in a United States registry of rheumatoid arthritis patients SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Malignancy; Rheumatoid arthritis; Registry; Validation ID NECROSIS FACTOR THERAPY; FACTOR ANTAGONISTS; LUNG-CANCER; RISK; LYMPHOMA; METHOTREXATE; DRUG; INCREASE; TRIALS; CLAIMS AB Background: Physician reporting is commonly used to ascertain adverse events or outcomes measured in epidemiologic studies. However, little is known on the accuracy of physician reported malignancies compared to pertinent medical record review in large cohort studies. Methods: The Consortium of Rheumatology Researchers of North America (CORRONA) registry gathers physician-completed questionnaires for rheumatoid arthritis (RA) patients, including request for information on incident malignancies, approximately every three months. For incident malignancies reported from October 1st, 2001, through December 31st, 2007, we retrospectively requested completion of a Targeted Adverse Event (TAE) form for additional information as well as primary source documents to adjudicate the malignancy reports. CORRONA has employed a prospective request for source documentation for these events since 2008. We classified each malignancy as definite, probable, possible, or not a malignancy. Results: From 20,837 RA patients enrolled in CORRONA, 461 incident malignancies were initially reported on physician questionnaires. After review of returned source documents with adjudication, 234 were deemed definite, 69 probable, 101 possible, and 57 not an incident malignancy. The positive predictive value (PPV) of initial physician report of a malignancy versus "definite or probable" malignancy based on adjudication was 0.66 (95% CI 0.61 - 0.70). The PPV was 0.68 (95% CI 0.63 - 0.72) when the subsequent TAE form also confirmed the presence of malignancy. When possible malignancies were included, the PPV of physician-reported malignancies without a subsequent TAE form increased to 0.86 (0.83 - 0.89), and with a subsequent TAE form, 0.89 (0.85-0.91). Conclusion: Twelve percent of initial physician reports of incident malignancy could not be confirmed with review of source documents. The most common reason for lack of confirmation was inability to obtain documents or insufficient data in source materials. These results suggest that timely collection of relevant medical records and an adjudication process are required to improve the accuracy of cancer reporting in epidemiologic studies. C1 [Fisher, Mark C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Furer, Victoria; Greenberg, Jeffrey D.] NYU, Hosp Joint Dis, Dept Rheumatol, New York, NY 10003 USA. [Hochberg, Marc C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Hochberg, Marc C.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Kremer, Joel M.] SUNY Albany, Albany Med Coll, Ctr Rheumatol, Albany, NY 12206 USA. [Curtis, Jeff R.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Reed, George] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. [Harrold, Leslie] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02120 USA. RP Fisher, MC (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mfisher6@partners.org FU NIH [K23AR054412, AR053351, K23AR053856, K24 AR 055989]; Arthritis Foundation; National Arthritis Research Foundation; Amgen; Roche/Genentech; Centecor; CORRONA; Abbott; Bristol Myers Squibb FX Dr. Fisher has nothing to disclose. Dr. Furer has nothing to disclose. Dr. Hochberg has consulted for Abbott Laboratories, Amgen, Bristol Myers Squibb, Genentech, UCB Inc. Dr. Greenberg receives salary support from research grants from the NIH (K23AR054412), the Arthritis Foundation and the National Arthritis Research Foundation, serves as Chief Scientific Officer for CORRONA and has served on Advisory Boards for Genentech and Pfizer. Dr. Kremer is the President of CORRONA, receives salary support. Dr. Curtis has consulted for or received honoraria from Roche/Genentech, UCB, Centecor, CORRONA, Amgen, and Pfizer, and has received research support from Amgen, Roche/Genentech, Centecor and CORRONA. Dr. Curtis also receives salary support from the NIH (AR053351). Dr. Harrold received support from the NIH (K23AR053856). She also has consulted for CORRONA. Dr. Solomon has received research support from Amgen and Abbott for rheumatoid arthritis research and has received support for an educational course from Bristol Myers Squibb. Dr. Solomon also receives salary support from the NIH for mentoring (K24 AR 055989). NR 24 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD MAY 31 PY 2012 VL 13 AR 85 DI 10.1186/1471-2474-13-85 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 978AW UT WOS:000306712100001 PM 22651246 ER PT J AU Shanmugam, NKN Ellenbogen, S Trebicka, E Wang, LJ Mukhopadhyay, S Lacy-Hulbert, A Gallini, CA Garrett, WS Cherayil, BJ AF Shanmugam, Nanda Kumar N. Ellenbogen, Shiri Trebicka, Estela Wang, Lijian Mukhopadhyay, Subhankar Lacy-Hulbert, Adam Gallini, Carey Ann Garrett, Wendy S. Cherayil, Bobby J. TI Tumor Necrosis Factor alpha Inhibits Expression of the Iron Regulating Hormone Hepcidin in Murine Models of Innate Colitis SO PLOS ONE LA English DT Article ID HEREDITARY HEMOCHROMATOSIS PROTEIN; ULCERATIVE-COLITIS; IN-VIVO; INFLAMMATION; HFE; DISEASE; GROWTH; STAT3; MACROPHAGES; HOMEOSTASIS AB Background: Abnormal expression of the liver peptide hormone hepcidin, a key regulator of iron homeostasis, contributes to the pathogenesis of anemia in conditions such as inflammatory bowel disease (IBD). Since little is known about the mechanisms that control hepcidin expression during states of intestinal inflammation, we sought to shed light on this issue using mouse models. Methodology/Principal Findings: Hepcidin expression was evaluated in two types of intestinal inflammation caused by innate immune activation-dextran sulfate sodium (DSS)-induced colitis in wild-type mice and the spontaneous colitis occurring in T-bet/Rag2-deficient (TRUC) mice. The role of tumor necrosis factor (TNF) alpha was investigated by in vivo neutralization, and by treatment of a hepatocyte cell line, as well as mice, with the recombinant cytokine. Expression and activation of Smad1, a positive regulator of hepcidin transcription, were assessed during colitis and following administration or neutralization of TNF alpha. Hepcidin expression progressively decreased with time during DSS colitis, correlating with changes in systemic iron distribution. TNF alpha inhibited hepcidin expression in cultured hepatocytes and non-colitic mice, while TNF alpha neutralization during DSS colitis increased it. Similar results were obtained in TRUC mice. These effects involved a TNF alpha-dependent decrease in Smad1 protein but not mRNA. Conclusions/Significance: TNF alpha inhibits hepcidin expression in two distinct types of innate colitis, with down-regulation of Smad1 protein playing an important role in this process. This inhibitory effect of TNF alpha may be superseded by other factors in the context of T cell-mediated colitis given that in the latter form of intestinal inflammation hepcidin is usually upregulated. C1 [Shanmugam, Nanda Kumar N.; Ellenbogen, Shiri; Trebicka, Estela; Wang, Lijian; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Boston, MA 02114 USA. [Mukhopadhyay, Subhankar; Lacy-Hulbert, Adam] Massachusetts Gen Hosp, Dept Pediat, Dev Immunol Lab, Boston, MA 02114 USA. [Mukhopadhyay, Subhankar] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Lacy-Hulbert, Adam; Garrett, Wendy S.; Cherayil, Bobby J.] Harvard Univ, Sch Med, Boston, MA USA. [Gallini, Carey Ann; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Gallini, Carey Ann; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shanmugam, NKN (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Boston, MA 02114 USA. EM cherayil@helix.mgh.harvard.edu OI Lacy-Hulbert, Adam/0000-0003-2162-0156 FU National Institutes of Health [R56AI089700, R01AI089700, RO1CA154426, K08AI078942]; Wellcome Trust Flexible Travel Award Fellowship FX The work was supported by grants from the National Institutes of Health to BJC (R56AI089700, R01AI089700) and to WSG (RO1CA154426, K08AI078942). SM was supported by a Wellcome Trust Flexible Travel Award Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 16 Z9 16 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 31 PY 2012 VL 7 IS 5 AR e38136 DI 10.1371/journal.pone.0038136 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959TY UT WOS:000305338500091 PM 22675442 ER PT J AU Ranieri, VM Thompson, BT Barie, PS Dhainaut, JF Douglas, IS Finfer, S Gardlund, B Marshall, JC Rhodes, A Artigas, A Payen, D Tenhunen, J Al-Khalidi, HR Thompson, V Janes, J Macias, WL Vangerow, B Williams, MD AF Ranieri, V. Marco Thompson, B. Taylor Barie, Philip S. Dhainaut, Jean-Francois Douglas, Ivor S. Finfer, Simon Gardlund, Bengt Marshall, John C. Rhodes, Andrew Artigas, Antonio Payen, Didier Tenhunen, Jyrki Al-Khalidi, Hussein R. Thompson, Vivian Janes, Jonathan Macias, William L. Vangerow, Burkhard Williams, Mark D. CA PROWESS-SHOCK Study Grp TI Drotrecogin Alfa (Activated) in Adults with Septic Shock SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MULTIPLE-ORGAN DYSFUNCTION; PLACEBO-CONTROLLED TRIAL; APACHE-II SCORE; SEVERE SEPSIS; PROTEIN-C; SURGICAL-PATIENTS; PROWESS TRIAL; UNITED-STATES; DEATH; CARE AB BACKGROUND There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 mu g per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. RESULTS At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P = 0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P = 0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P = 0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P = 0.81). CONCLUSIONS DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.) C1 [Ranieri, V. Marco] Univ Turin, Osped S Giovanni Battista Molinette, Turin, Italy. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Barie, Philip S.] Weill Cornell Med Coll, Dept Surg, New York, NY USA. [Barie, Philip S.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Dhainaut, Jean-Francois] Paris Descartes Univ, Royal Hosp, Paris, France. [Payen, Didier] Univ Paris Diderot, Paris, France. [Payen, Didier] Hop Lariboisiere, AP HP, Dept Anesthesie Reanimat SMUR, F-75475 Paris, France. [Douglas, Ivor S.] Univ Colorado, Sch Med, Denver, CO USA. [Finfer, Simon] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Finfer, Simon] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Gardlund, Bengt] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. [Marshall, John C.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Inst, Dept Surg, Toronto, ON M5B 1W8, Canada. [Marshall, John C.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Inst, Dept Crit Care Med, Toronto, ON M5B 1W8, Canada. [Rhodes, Andrew] St Georges Healthcare NHS Trust, London, England. [Artigas, Antonio] St Georges Univ, London, England. [Artigas, Antonio] Univ Autonoma Barcelona, Univ Parc Tauli, CIBER Enfermedades Resp, Crit Care Ctr,Hosp Sabadell, Sabadell, Spain. [Tenhunen, Jyrki] Uppsala Univ, Dept Surg Sci Anaesthesiol & Intens Care, Uppsala, Sweden. [Al-Khalidi, Hussein R.; Thompson, Vivian] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Janes, Jonathan; Macias, William L.; Vangerow, Burkhard; Williams, Mark D.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RI Ruiz-Rodriguez, Juan Carlos/H-7703-2012; Pickkers, R.P./H-8080-2014; Leditschke, Isabel/M-1186-2015; Asfar, Pierre/K-1402-2015; Sramek, Vladimir/M-2152-2016; Betbese, Antoni/H-3419-2013; Malbrain, Manu/B-3680-2017; OI Ferguson, Niall/0000-0002-6213-5264; Rello, Jordi/0000-0003-0676-6210; Van Haren, Frank/0000-0001-8037-4229; Leditschke, Isabel/0000-0003-2212-2140; Betbese, Antoni/0000-0002-9059-4046; Malbrain, Manu/0000-0002-1816-5255; Della Corte, Francesco/0000-0003-1736-2318; , /0000-0002-4157-5148; Whitehouse, Tony/0000-0002-4387-3421; Douglas, Ivor/0000-0002-4541-1431 FU Eli Lilly; Abbott; Sanofi-Aventis; Immunetrics; US Biotest; Sirius Genomics; Eisai; Agennix; Idaho Technology; Roche Diagnostics; Bayer; Vertex Technologies; Pfizer; Daiichi Sankyo; Hoffmann-La Roche; BioMerieux; Edwards; LiDCO; Covidien; Brahms; Naturalia et Biologia FX Dr. Ranieri reports serving as a member of a data and safety monitoring board for Biotest and an advisory board member for Hemodec and Maquet; Dr. Thompson, serving as the chair of a data and safety monitoring board for AstraZeneca and as an advisory board member for Hemodec, receiving consulting fees from Abbott, Sanofi-Aventis, Immunetrics, US Biotest, Sirius Genomics, and Eli Lilly; Dr. Barie, receiving consulting fees from Eisai and lecture fees from Eli Lilly; Dr. Douglas, receiving grant support from Eli Lilly, Eisai, and Agennix and serving as cochair for the International Guidelines Committee for the 2012 Surviving Sepsis Campaign; Dr. Finfer, receiving consulting fees from Eisai, being a member of the International Sepsis Forum (ISF), and receiving travel support from ISF corporate sponsors; Dr. Marshall, receiving consulting fees from Eisai, Idaho Technology, Roche Diagnostics, Bayer, Vertex Technologies, Pfizer, Daiichi Sankyo, and Hoffmann-La Roche, receiving grant support and travel expenses from BioMerieux, serving as a member of the ISF and receiving travel support from ISF corporate sponsors, serving as a member of the Center for Sepsis Control and Care at the University of Jena and as a member of the data and safety monitoring board for Artisan Pharma, Leo Pharma, Celgene Therapeutics, and Therapeutic Monitoring Systems, and serving as a steering committee member for Spectral Diagnostics and Eisai; Dr. Rhodes, serving on advisory boards for LiDCO and BioMerieux and receiving lecture fees from Edwards, LiDCO, and Covidien; all the preceding authors, or their institutions, received financial support from Eli Lilly for time spent performing committee activities and for travel; Dr. Artigas, receiving travel support and lecture fees and grant support and support for patient recruitment (through his institution) from Eli Lilly, serving on advisory boards for Gambro and Hemodec, and receiving consulting fees from Brahms; Dr. Payen, serving on an advisory board for Homeostasie Consulting and receiving consulting and lecture fees from Homeostasie Consulting and institutional grant support from Naturalia et Biologia; Dr. Tenhunen, receiving institutional grant support for lectures, travel expenses, and data analysis from Eli Lilly; Dr. Al-Khalidi and Ms. Thompson, being employees of the Duke Clinical Research Institute, which received financial support for statistical analysis, preparation of study reports, manuscript review and writing, and travel from Eli Lilly; and Drs. Janes, Macias, Vangerow, and Williams, being current or former employees of and having an equity interest in Eli Lilly. No other potential conflict of interest relevant to this article was reported. NR 39 TC 437 Z9 459 U1 3 U2 48 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 31 PY 2012 VL 366 IS 22 BP 2055 EP 2064 DI 10.1056/NEJMoa1202290 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 949YE UT WOS:000304613400005 PM 22616830 ER PT J AU Batchelor, TT Sorensen, AG Louis, DN AF Batchelor, Tracy T. Sorensen, A. Gregory Louis, David N. TI Case 17-2012: A 54-Year-Old Man with Visual-Field Loss and a Mass in the Brain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NEWLY-DIAGNOSED GLIOBLASTOMA; PROMOTER METHYLATION STATUS; TEMOZOLOMIDE; RADIOTHERAPY; CONCOMITANT; ADJUVANT; SURGERY; GLIOMAS; TRIAL C1 [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Sorensen, A. Gregory] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Millennium; Pfizer; AstraZeneca; Merck; Imedex; Educational Concepts Group; Strategic Edge Communications; BayerScheringPharma; Bristol-Myers Squibb; BiogenIdec; Merrimack Pharmaceuticals; Olea Medical; Mitsubishi Pharma; GE Healthcare; Regeneron; Novartis; Roche; Siemens Healthcare; Takeda; ACR-Image Metrix; Bayer FX Dr. Batchelor reports receiving payment for advisory board membership from Roche, Spectrum, and Amgen; consulting fees from Millennium; grant support from Pfizer and AstraZeneca; lecture fees from Merck, Imedex, Educational Concepts Group, and Strategic Edge Communications; and payment for the development of educational presentations from UpToDate. Dr. Sorensen reports being an employee of Siemens Healthcare; receiving consulting fees from BayerScheringPharma, Bristol-Myers Squibb, BiogenIdec, Merrimack Pharmaceuticals, Olea Medical, Mitsubishi Pharma, GE Healthcare, Regeneron, Novartis, Roche, Siemens Healthcare, Takeda, and AstraZeneca; receiving lecture fees from ACR-Image Metrix; receiving income from patents (owned by Massachusetts General Hospital) for neuroradiology-related image acquisition and analysis; receiving royalties from Massachusetts General Hospital for licensure of brain perfusion software; serving as an expert witness for Kit regarding the imaging appearance of carbon monoxide poisoning; receiving payment from the International Center for Postgraduate Medical Education for preparation of an online course on the use of MRI contrast agents, supported by a grant from Bayer; and owning stock in Catalyst Medical. Dr. Louis reports receiving payment for expert opinion on the results of genetic testing in brain tumors from Rohm and Haas. No other potential conflict of interest relevant to this article was reported. NR 13 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 31 PY 2012 VL 366 IS 22 BP 2112 EP 2120 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 949YE UT WOS:000304613400013 PM 22646634 ER PT J AU Janas, MM Novina, CD AF Janas, Maja M. Novina, Carl D. TI Not lost in translation: stepwise regulation of microRNA targets SO EMBO JOURNAL LA English DT Editorial Material ID MESSENGER-RNA; PROTEIN-SYNTHESIS; LET-7 MICRORNA; IN-VITRO; INITIATION; DEADENYLATION; INHIBITION; ZEBRAFISH AB MicroRNAs (miRNAs) are endogenous, similar to 22-nucleotide-long, noncoding RNAs that play critical roles in physiology and disease via mechanisms that remain obscure. Although numerous studies implicate miRNAs in repression of translation, more recent reports suggest that the major role of miRNAs is in reduction of target mRNA stability. Because mRNA translation and stability are intimately connected, it has been a challenge to establish whether miRNAs induce translational repression, mRNA decay, or both. If miRNAs reduce both mRNA translation and stability, the timing and contribution of each process to overall repression is unclear. Indeed, it has been debated whether mRNA decay is a cause or consequence of miRNA-mediated translational repression. On the other hand, if these events are mutually exclusive, what determines which mechanism is used? In a recent issue of Science, Bazzini et al (2012) use genome-wide ribosome footprinting and RNA sequencing (RNA-Seq) to demonstrate that in developing zebrafish embryos, miR-430 naturally represses translation initiation of target mRNAs, followed by their deadenylation and decay. C1 [Janas, Maja M.; Novina, Carl D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Janas, Maja M.; Novina, Carl D.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Janas, Maja M.; Novina, Carl D.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Novina, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu NR 13 TC 7 Z9 7 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 30 PY 2012 VL 31 IS 11 BP 2446 EP 2447 DI 10.1038/emboj.2012.119 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 949UA UT WOS:000304600300004 PM 22522704 ER PT J AU Moon, H Park, HE Kang, J Lee, H Cheong, C Lim, YT Ihm, SH Seung, KB Jaffer, FA Narula, J Chang, K Hong, KS AF Moon, Hyeyoung Park, Hyo Eun Kang, Jongeun Lee, Hyunseung Cheong, Chaejoon Lim, Yong Taik Ihm, Sang-Hyun Seung, Ki-Bae Jaffer, Farouc A. Narula, Jagat Chang, Kiyuk Hong, Kwan Soo TI Noninvasive Assessment of Myocardial Inflammation by Cardiovascular Magnetic Resonance in a Rat Model of Experimental Autoimmune Myocarditis SO CIRCULATION LA English DT Article DE contrast media; inflammation; macrophage; magnetic resonance imaging; myocarditis ID VIRAL MYOCARDITIS; NANOPARTICLES; REJECTION; DIAGNOSIS; PLAQUE; DEATH; CELLS AB Background-Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis. Methods and Results-The feasibility of cardiovascular magnetic resonance (CMR) imaging with magneto-fluorescent nanoparticles (MNPs) for detection of myocarditis and its effectiveness in discriminating inflammation grades were assessed in experimental autoimmune myocarditis (EAM) (n = 65) and control (n = 10) rats. After undergoing CMR, rats were administered with MNPs, followed by a second CMR 24 hours later. Head-to-head comparison of MNP-CMR with T-2-weighted, early and late gadolinium enhancement CMR was performed in additional EAM (n = 10) and control (n = 5) rats. Contrast-to-noise ratios were measured and compared between groups. Flow cytometry and microscopy demonstrated that infiltrating inflammatory cells engulfed MNPs, resulting in altered myocardial T-2* effect. Changes in contrast-to-noise ratio between pre- and post-MNP CMR were significantly greater in EAM rats (1.08 +/- 0.10 versus 0.48 +/- 0.20; P < 0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (P < 0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%, P < 0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats. Conclusions-Magneto-fluorescent nanoparticle CMR permitted effective visualization of myocardial inflammatory cellular infiltrates and distinction of the extent of inflammation compared with conventional CMR in a preclinical model of EAM. Magneto-fluorescent nanoparticle CMR performs best in EAM rats with at least moderate inflammatory response. (Circulation. 2012; 125: 2603-2612.) C1 [Moon, Hyeyoung; Kang, Jongeun; Lee, Hyunseung; Cheong, Chaejoon; Hong, Kwan Soo] Korea Basic Sci Inst, Div MR Res, Ochang Eup 363883, Cheongwon, South Korea. [Moon, Hyeyoung; Hong, Kwan Soo] Univ Sci & Technol, Dept Bioanalyt Sci, Taejon, South Korea. [Park, Hyo Eun; Ihm, Sang-Hyun; Seung, Ki-Bae; Chang, Kiyuk] Seoul St Marys Hosp, Ctr Cardiovasc, Seoul, South Korea. [Chang, Kiyuk] Catholic Univ Korea, Coll Med, Dept Cardiovasc Med, Ctr Cardiovasc, Seoul 137701, South Korea. [Kang, Jongeun; Lim, Yong Taik; Hong, Kwan Soo] Chungnam Natl Univ, Grad Sch Analyt Sci & Technol, Taejon, South Korea. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Div Cardiol, Cardiovasc Res Ctr,Massachusetts Gen Hosp, Charlestown, MA USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Charlestown, MA USA. [Narula, Jagat] Mt Sinai Sch Med, Zena & Michael Wiener Cardiovasc Inst, New York, NY USA. RP Hong, KS (reprint author), Korea Basic Sci Inst, Div MR Res, 804-1 Yangcheong Ri, Ochang Eup 363883, Cheongwon, South Korea. EM kiyuk@catholic.ac.kr; kshong@kbsi.re.kr OI Ihm, Sang Hyun/0000-0001-5017-5421; Jaffer, Farouc/0000-0001-7980-384X FU National Research Foundation of Korea [2011-0029263, 2009-008146]; Korea Basic Science Institute [T31403]; Ministry of Health and Welfare [A090604, A092258] FX This work was supported by grants from the National Research Foundation of Korea (to Dr Hong, 2011-0029263 and 2009-008146), Korea Basic Science Institute (to Dr Hong, T31403), and the Korea Health Technology R&D Project, Ministry of Health and Welfare (to Dr Chang, A090604 and A092258). NR 35 TC 16 Z9 19 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2012 VL 125 IS 21 BP 2603 EP U343 DI 10.1161/CIRCULATIONAHA.111.075283 PG 20 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981MQ UT WOS:000306972800017 PM 22550157 ER PT J AU Weiner, RB Wang, F Berkstresser, B Kim, J Wang, TJ Lewis, GD Hutter, AM Picard, MH Baggish, AL AF Weiner, Rory B. Wang, Francis Berkstresser, Brant Kim, Jonathan Wang, Thomas J. Lewis, Gregory D. Hutter, Adolph M., Jr. Picard, Michael H. Baggish, Aaron L. TI Regression of "Gray Zone" Exercise-Induced Concentric Left Ventricular Hypertrophy During Prescribed Detraining SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID DISEASE C1 [Weiner, Rory B.; Wang, Francis; Berkstresser, Brant; Kim, Jonathan; Wang, Thomas J.; Lewis, Gregory D.; Hutter, Adolph M., Jr.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [K23 HL091106] NR 5 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 29 PY 2012 VL 59 IS 22 BP 1992 EP 1994 DI 10.1016/j.jacc.2012.01.057 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 949QR UT WOS:000304591300014 PM 22624842 ER PT J AU Schumacher, J Haslinger, R Pipa, G AF Schumacher, Johannes Haslinger, Robert Pipa, Gordon TI Statistical modeling approach for detecting generalized synchronization SO PHYSICAL REVIEW E LA English DT Article ID SYSTEMS; PHASE; CHAOS AB Detecting nonlinear correlations between time series presents a hard problem for data analysis. We present a generative statistical modeling method for detecting nonlinear generalized synchronization. Truncated Volterra series are used to approximate functional interactions. The Volterra kernels are modeled as linear combinations of basis splines, whose coefficients are estimated via l(1) and l(2) regularized maximum likelihood regression. The regularization manages the high number of kernel coefficients and allows feature selection strategies yielding sparse models. The method's performance is evaluated on different coupled chaotic systems in various synchronization regimes and analytical results for detecting m : n phase synchrony are presented. Experimental applicability is demonstrated by detecting nonlinear interactions between neuronal local field potentials recorded in different parts of macaque visual cortex. C1 [Schumacher, Johannes; Haslinger, Robert; Pipa, Gordon] Univ Osnabruck, Inst Cognit Sci, D-4500 Osnabruck, Germany. [Schumacher, Johannes; Haslinger, Robert; Pipa, Gordon] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Schumacher, Johannes; Haslinger, Robert; Pipa, Gordon] Massachusetts Gen Hosp, Charlestown, MA USA. [Schumacher, Johannes; Haslinger, Robert; Pipa, Gordon] Frankfurt Inst Adv Studies, Frankfurt, Germany. RP Schumacher, J (reprint author), Univ Osnabruck, Inst Cognit Sci, D-4500 Osnabruck, Germany. EM joschuma@uos.de; robhh@nmr.mgh.harvard.edu; gpipa@uos.de RI Pipa, Gordon/M-1813-2014 OI Pipa, Gordon/0000-0002-3416-2652 FU EU [FET-Open 240763]; NIH [K25-NS052422-02] FX We thank Sergio Neuenschwander for providing the local field potential recordings. We thank Ingo Fischer and Miguel C. Soriano for providing the simulated Mackey-Glass data. This work was partially supported by the EU-project PHOCUS (FET-Open 240763) (J.S., G. P.) and the NIH Grant No. K25-NS052422-02 (R.H.). NR 21 TC 4 Z9 4 U1 0 U2 3 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD MAY 29 PY 2012 VL 85 IS 5 AR 056215 DI 10.1103/PhysRevE.85.056215 PN 2 PG 7 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 948VG UT WOS:000304530300005 PM 23004851 ER PT J AU Rajani, DK Walch, M Martinvalet, D Thomas, MP Lieberman, J AF Rajani, Danielle K. Walch, Michael Martinvalet, Denis Thomas, Marshall P. Lieberman, Judy TI Alterations in RNA processing during immune-mediated programmed cell death SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; cytotoxic T lymphocyte ID FAS-INDUCED APOPTOSIS; MESSENGER-RNA; HUMAN GRANZYME; PROTEOME ANALYSIS; BINDING PROTEINS; HEAT-SHOCK; CLEAVAGE; IDENTIFICATION; COMPLEX; TARGETS AB During immune-mediated death, death-inducing granzyme (Gzm) proteases concentrate in the nucleus of cells targeted for immune elimination, suggesting that nuclear processes are important targets. Here we used differential 2D proteomics of GzmA-treated nuclei to identify potential GzmA substrates. Of 44 candidates, 33 were RNA-binding proteins important in posttranscriptional RNA processing, including 14 heterogeneous nuclear ribonucleoproteins (hnRNP). Multiple hnRNPs were degraded in cells undergoing GzmA-, GzmB-, or caspase-mediated death. GzmA and caspase activation impaired nuclear export of newly synthesized RNA and disrupted pre-mRNA splicing. Expressing GzmA-resistant hnRNP A1 inhibited GzmA-mediated cell death and rescued pre-mRNA splicing, suggesting that hnRNP A1 is an important GzmA substrate. Cellular stresses are known to inhibit initiation of cap-dependent translation. Disrupting pre-mRNA processing should block further new protein synthesis and promote death by interfering with pathways induced to protect cells from death. C1 [Rajani, Danielle K.; Walch, Michael; Martinvalet, Denis; Thomas, Marshall P.; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston, Boston, MA 02115 USA. [Rajani, Danielle K.; Walch, Michael; Martinvalet, Denis; Thomas, Marshall P.; Lieberman, Judy] Harvard Univ, Sch Med, Program Mol & Cellular Med, Childrens Hosp Boston, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU National Science Foundation; Kurt und Senta Herrmann-Foundation; National Institutes of Health [AI45587] FX We thank Gideon Dreyfuss for hnRNP antibodies and Arlene Sharpe, Paul Anderson, Tom Kirchhausen, Melissa Moore and members of the J.L. laboratory for helpful discussions. This work was supported by National Science Foundation predoctoral fellowships (to D. K. R. and M. P. T.), a Kurt und Senta Herrmann-Foundation fellowship (to M. W.), and National Institutes of Health Grant AI45587 (to J.L.). NR 29 TC 11 Z9 11 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 29 PY 2012 VL 109 IS 22 BP 8688 EP 8693 DI 10.1073/pnas.1201327109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953PD UT WOS:000304881700067 PM 22589304 ER PT J AU Straume, O Shimamura, T Lampa, MJG Carretero, J Oyan, AM Jia, D Borgman, CL Soucheray, M Downing, SR Short, SM Kang, SY Wang, SM Chen, L Collett, K Bachmann, I Wong, KK Shapiro, GI Kalland, KH Folkman, J Watnick, RS Akslen, LA Naumov, GN AF Straume, Oddbjorn Shimamura, Takeshi Lampa, Michael J. G. Carretero, Julian Oyan, Anne M. Jia, Di Borgman, Christa L. Soucheray, Margaret Downing, Sean R. Short, Sarah M. Kang, Soo-Young Wang, Souming Chen, Liang Collett, Karin Bachmann, Ingeborg Wong, Kwok-Kin Shapiro, Geoffrey I. Kalland, Karl Henning Folkman, Judah Watnick, Randolph S. Akslen, Lars A. Naumov, George N. TI Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NF kappa B; STAT3 ID FIBROBLAST-GROWTH-FACTOR; HUMAN TUMOR DORMANCY; ENDOTHELIAL-CELLS; ANGIOGENIC SWITCH; EXPRESSION SIGNATURE; HEAT-SHOCK-PROTEIN-27; PROLIFERATION; MELANOCYTES; MECHANISMS; APOPTOSIS AB The mechanisms underlying tumor dormancy have been elusive and not well characterized. We recently published an experimental model for the study of human tumor dormancy and the role of angiogenesis, and reported that the angiogenic switch was preceded by a local increase in VEGF-A and basic fibroblast growth factor. In this breast cancer xenograft model (MDA-MB-436 cells), analysis of differentially expressed genes revealed that heat shock protein 27 (HSP27) was significantly up-regulated in angiogenic cells compared with nonangiogenic cells. The effect of HSP27 down-regulation was further evaluated in cell lines, mouse models, and clinical datasets of human patients with breast cancer and melanoma. Stable down-regulation of HSP27 in angiogenic tumor cells was followed by long-term tumor dormancy in vivo. Strikingly, only 4 of 30 HSP27 knockdown xenograft tumors initiated rapid growth after day 70, in correlation with a regain of HSP27 protein expression. Significantly, no tumors escaped from dormancy without HSP27 expression. Down-regulation of HSP27 was associated with reduced endothelial cell proliferation and decreased secretion of VEGF-A, VEGF-C, and basic fibroblast growth factor. Conversely, overexpression of HSP27 in nonangiogenic cells resulted in expansive tumor growth in vivo. By clinical validation, strong HSP27 protein expression was associated with markers of aggressive tumors and decreased survival in patients with breast cancer and melanoma. An HSP27-associated gene expression signature was related to molecular subgroups and survival in breast cancer. Our findings suggest a role for HSP27 in the balance between tumor dormancy and tumor progression, mediated by tumor-vascular interactions. Targeting HSP27 might offer a useful strategy in cancer treatment. C1 [Straume, Oddbjorn; Lampa, Michael J. G.; Jia, Di; Downing, Sean R.; Short, Sarah M.; Kang, Soo-Young; Wang, Souming; Folkman, Judah; Watnick, Randolph S.; Akslen, Lars A.; Naumov, George N.] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Straume, Oddbjorn; Lampa, Michael J. G.; Jia, Di; Downing, Sean R.; Short, Sarah M.; Kang, Soo-Young; Wang, Souming; Folkman, Judah; Watnick, Randolph S.; Akslen, Lars A.; Naumov, George N.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Straume, Oddbjorn; Collett, Karin; Bachmann, Ingeborg; Kalland, Karl Henning; Akslen, Lars A.] Univ Bergen, Sect Pathol, Gade Inst, N-5021 Bergen, Norway. [Shimamura, Takeshi; Carretero, Julian; Borgman, Christa L.; Chen, Liang; Wong, Kwok-Kin; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Shimamura, Takeshi; Carretero, Julian; Wong, Kwok-Kin; Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shimamura, Takeshi; Soucheray, Margaret] Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Inst Oncol, Maywood, IL 60153 USA. [Carretero, Julian] Univ Valencia, Dept Physiol, E-46100 Valencia, Spain. [Oyan, Anne M.; Kalland, Karl Henning] Haukeland Hosp, Dept Microbiol & Immunol, N-5021 Bergen, Norway. [Chen, Liang; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02215 USA. [Akslen, Lars A.] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. RP Akslen, LA (reprint author), Childrens Hosp, Vasc Biol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM lars.akslen@gades.uib.no; george_naumov@merck.com RI Jia, Di/E-6943-2013; Carretero, Julian/N-5214-2014; Kalland, Karl-Henning/B-9445-2017; Akslen, Lars /C-1202-2017; Straume, Oddbjorn/C-2186-2017; OI Carretero, Julian/0000-0001-7269-8506; Kalland, Karl-Henning/0000-0003-4486-2334; Akslen, Lars /0000-0003-2710-9543; Straume, Oddbjorn/0000-0001-8867-3645; wong, kwok kin/0000-0001-6323-235X FU Helse Vest [911401, 911500, 15126600, 911403]; Norwegian Cancer Society [HS02-2008-0188, 94070, 419328 71512-PR-2006-0356]; Unger Vetlesen Foundation; Dana-Farber Cancer Institute; Dana-Farber/Harvard Cancer Center, National Institutes of Health (NIH) [P50 CA090578]; Research Council of Norway [185676/V40, 154942/310, 161231/V40, 163920/V50]; NIH [P01CA045548]; Breast Cancer Research Foundation; Department of Defense [W81XWH-04-1-0316] FX We thank Gerd Lillian Hallseth, Hua My Hoang, and Bendik Nordanger for excellent technical assistance and Marsha A. Moses and Alexis Mitsialis of Children's Hospital Boston for helpful comments and experimental support. The work of O.S. was supported by Helse Vest, the Norwegian Cancer Society, and the Unger Vetlesen Foundation. T. S. was supported by the Dana-Farber Cancer Institute Claudia Adams Barr Program in Innovative Basic Cancer Research. G. I. S. was supported by Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Lung Cancer, National Institutes of Health (NIH) Grant P50 CA090578. The work of K. H. K. was supported by Research Council of Norway Grant 185676/V40, Helse Vest Grants 911401 and 911500, and Norwegian Cancer Society Grant HS02-2008-0188. The work of J.M.F. was funded by NIH Grant P01CA045548, the Breast Cancer Research Foundation, and Department of Defense Breast Cancer Innovator Award W81XWH-04-1-0316. L. A. A. was supported by Research Council of Norway Grants 154942/310, 161231/V40, and 163920/V50; Helse Vest Grants 15126600 and 911403; the Unger Vetlesen Foundation; and Norwegian Cancer Society Grants 94070 and 419328 71512-PR-2006-0356. NR 31 TC 50 Z9 52 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 29 PY 2012 VL 109 IS 22 BP 8699 EP 8704 DI 10.1073/pnas.1017909109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 953PD UT WOS:000304881700069 PM 22589302 ER PT J AU Seyedali, M Czerniecki, JM Morgenroth, DC Hahn, ME AF Seyedali, Mahyo Czerniecki, Joseph M. Morgenroth, David C. Hahn, Michael E. TI Co-contraction patterns of trans-tibial amputee ankle and knee musculature during gait SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article DE Electromyography; Myoelectric control; Trans-tibial amputees; Activation patterns; Muscle amplitude ID MUSCLE-ACTIVITY; WALKING SPEEDS; EMG PROFILES; CHILDREN; PROSTHESIS; LOCOMOTION; INDEX; JOINT AB Background: Myoelectric control of upper extremity powered prostheses has been used clinically for many years, however this approach has not been fully developed for lower extremity prosthetic devices. With the advent of powered lower extremity prosthetic components, the potential role of myoelectric control systems is of increasing importance. An understanding of muscle activation patterns and their relationship to functional ambulation is a vital step in the future development of myoelectric control. Unusual knee muscle co-contractions have been reported in both limbs of trans-tibial amputees. It is currently unknown what differences exist in co-contraction between trans-tibial amputees and controls. This study compares the activation and co-contraction patterns of the ankle and knee musculature of trans-tibial amputees (intact and residual limbs), and able-bodied control subjects during three speeds of gait. It was hypothesized that residual limbs would have greater ankle muscle co-contraction than intact and able-bodied control limbs and that knee muscle co-contraction would be different among all limbs. Lastly it was hypothesized that the extent of muscle co-contraction would increase with walking speed. Methods: Nine unilateral traumatic trans-tibial amputees and five matched controls participated. Surface electromyography recorded activation from the Tibialis Anterior, Medial Gastrocnemius, Vastus Lateralis and Biceps Femoris of the residual, intact and control limbs. A series of filters were applied to the signal to obtain a linear envelope of the activation patterns. A co-contraction area (ratio of the integrated agonist and antagonist activity) was calculated during specific phases of gait. Results: Co-contraction of the ankle muscles was greater in the residual limb than in the intact and control limbs during all phases of gait. Knee muscle co-contraction was greater in the residual limb than in the control limb during all phases of gait. Conclusion: Co-contractions may represent a limb stiffening strategy to enhance stability during phases of initial foot-contact and single limb support. These strategies may be functionally necessary for amputee gait; however, the presence of co-contractions could confound future development of myoelectric controls and should thus be accounted for. C1 [Seyedali, Mahyo; Czerniecki, Joseph M.; Morgenroth, David C.; Hahn, Michael E.] VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. [Seyedali, Mahyo; Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98105 USA. [Czerniecki, Joseph M.; Morgenroth, David C.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Hahn, ME (reprint author), VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mhahn@uoregon.edu OI Morgenroth, David/0000-0002-0226-7775 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; Department of Defense [W81XWH-09-2-0142] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. Additionally, this research was funded by a Department of Defense grant (W81XWH-09-2-0142). We gratefully acknowledge the supporting efforts of Janice Pecoraro and Elise Wright. NR 35 TC 5 Z9 5 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD MAY 28 PY 2012 VL 9 AR 29 DI 10.1186/1743-0003-9-29 PG 9 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 026IJ UT WOS:000310268300001 PM 22640660 ER PT J AU Kumar, N Bashar, Q Reddy, N Sengupta, J Ananthakrishnan, A Schroeder, A Hogan, WJ Venkatesan, T AF Kumar, Nilay Bashar, Qumseya Reddy, Naveen Sengupta, Jyotirmoy Ananthakrishnan, Ashwin Schroeder, Abigail Hogan, Walter J. Venkatesan, Thangam TI Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms - pediatric versus adult? SO BMC GASTROENTEROLOGY LA English DT Article DE Motility; Cyclic vomiting; Nausea; Abdominal pain ID CANNABINOID HYPEREMESIS; AMITRIPTYLINE; MANAGEMENT; DISORDERS; MIGRAINE; THERAPY AB Background: Cyclic Vomiting Syndrome (CVS) is a well-recognized functional gastrointestinal disorder in children but its presentation is poorly understood in adults. Genetic differences in pediatric-onset (presentation before age 18) and adult-onset CVS have been reported recently but their clinical features and possible differences in response to therapy have not been well studied. Methods: This was a retrospective review of 101 CVS patients seen at the Medical College of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the diagnosis of CVS. Results: Our study population comprised of 29(29%) pediatric-onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 +/- 7 years) in the pediatric-onset group when compared to (5 +/- 7 years) adultonset CVS group (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group compared to adultonset patients (0% vs. 23%, p = 0.004). Aside from these differences, the two groups were similar with regards to their clinical features and the time of onset of symptoms did not predict response to standard treatment. The majority of patients (86%) responded to treatment with tricyclic antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine. Non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of emergency department visits in the year prior to presentation, presence of disability and non-compliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response. (88% vs. 38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05). Conclusion: Despite reported genetic differences, the clinical features and response to standard therapy in pediatric-and adult-onset CVS were mostly similar. Most patients (86%) responded to therapy and compliance was the only factor associated with a response. C1 [Kumar, Nilay; Sengupta, Jyotirmoy; Schroeder, Abigail; Hogan, Walter J.; Venkatesan, Thangam] Med Coll Wisconsin, Dept Gastroenterol & Hepatol, Milwaukee, WI 53226 USA. [Bashar, Qumseya] Mayo Clin Florida, Jacksonville, FL USA. [Reddy, Naveen] Wayne State Univ, Detroit, MI USA. [Ananthakrishnan, Ashwin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Venkatesan, T (reprint author), Med Coll Wisconsin, Dept Gastroenterol & Hepatol, 4th Floor,Froedtert E Bldg,9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM tvenkate@mcw.edu NR 24 TC 11 Z9 13 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-230X J9 BMC GASTROENTEROL JI BMC Gastroenterol. PD MAY 28 PY 2012 VL 12 AR 52 DI 10.1186/1471-230X-12-52 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 006MB UT WOS:000308822200001 PM 22639867 ER PT J AU Zhou, C Kirtane, T Tsai, TH Lee, HC Adler, DC Schmitt, JM Huang, Q Fujimoto, JG Mashimo, H AF Zhou, Chao Kirtane, Tejas Tsai, Tsung-Han Lee, Hsiang-Chieh Adler, Desmond C. Schmitt, Joseph M. Huang, Qin Fujimoto, James G. Mashimo, Hiroshi TI Cervical inlet patch-optical coherence tomography imaging and clinical significance SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Cervical inlet patch; Heterotopic gastric mucosa; Optical coherence tomography; Optical biopsy; Barrett's esophagus ID HETEROTOPIC GASTRIC-MUCOSA; HIGH-GRADE DYSPLASIA; UPPER ESOPHAGUS; BARRETTS-ESOPHAGUS; 3-DIMENSIONAL ENDOMICROSCOPY; PRIMARY ADENOCARCINOMA; INTESTINAL METAPLASIA; PROXIMAL ESOPHAGUS; GI TRACT; PREVALENCE AB AIM: To demonstrate the feasibility of optical coherence tomography (OCT) imaging in differentiating cervical inlet patch (UP) from normal esophagus, Barrett's esophagus (BE), normal stomach and duodenum. METHODS: This study was conducted at the Veterans Affairs Boston Healthcare System (VABHS). Patients undergoing standard esophagogastroduodenoscopy at VABHS, including one patient with CIP, one representative patient with BE and three representative normal subjects were included. White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system. The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal (GI) tract. Standard hematoxylin and eosin (H and E) histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data. RESULTS: CIP was observed from a 68-year old male with gastroesophageal reflux disease. The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy. OCT imaging over the CIP region showed columnar epithelium structure, which clearly contrasted the squamous epithelium structure from adjacent normal esophagus. 3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus, BE, normal stomach, and normal duodenum bulb. Microstructures, such as squamous epithelium, lamina propria, muscularis mucosa, muscularis propria, esophageal glands, Barrett's glands, gastric mucosa, gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology. These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time. CONCLUSION: We demonstrate in situ evaluation of CIP microstructures using 3D-OCT, which may be a useful tool for future diagnosis and follow-up of patients with CIP. (C) 2012 Baishideng. All rights reserved. C1 [Kirtane, Tejas; Huang, Qin; Mashimo, Hiroshi] Harvard Univ, Sch Med, Gastroenterol Sect, VA Boston Healthcare Syst, Boston, MA 02131 USA. [Zhou, Chao; Tsai, Tsung-Han; Lee, Hsiang-Chieh; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. [Adler, Desmond C.; Schmitt, Joseph M.] Light Lab Imaging St Jude Med Inc, Westford, MN 55117 USA. RP Mashimo, H (reprint author), Harvard Univ, Sch Med, Gastroenterol Sect, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02131 USA. EM hmashimo@hms.harvard.edu RI Zhou, Chao/A-1327-2007; OI Tsai, Tsung-Han/0000-0002-2306-2269 FU VA Boston Healthcare System; NIH [R01-CA75289-14, K99-EB010071-01A1]; Air Force Office of Scientific Research [FA9550-10-1-0063]; Medical Free Electron Laser Program [FA9550-10-1-0551]; MIT/CIMIT FX Supported by The VA Boston Healthcare System and NIH grants R01-CA75289-14, to Fujimoto JG and Mashimo H; and K99-EB010071-01A1, to Zhou C; Air Force Office of Scientific Research contract FA9550-10-1-0063, to Fujimoto JG; Medical Free Electron Laser Program contract FA9550-10-1-0551, to Fujimoto JG; and the MIT/CIMIT Medical Engineering Fellowship, to Tsai TH NR 57 TC 4 Z9 5 U1 1 U2 5 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAY 28 PY 2012 VL 18 IS 20 BP 2502 EP 2510 DI 10.3748/wjg.v18.i20.2502 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 952HC UT WOS:000304782100007 PM 22654447 ER PT J AU Nathan, DM AF Nathan, David M. TI Understanding the Long-term Benefits and Dangers of Intensive Therapy of Diabetes SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID MICROVASCULAR COMPLICATIONS; GLUCOSE CONTROL; MELLITUS; RISK C1 Harvard Univ, Diabet Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Harvard Univ, Diabet Unit, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,Ste 340, Boston, MA 02114 USA. EM dnathan@partners.org NR 10 TC 4 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2012 VL 172 IS 10 BP 769 EP 770 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 948FK UT WOS:000304488800003 PM 22636821 ER PT J AU Pham-Kanter, G Alexander, GC Nair, K AF Pham-Kanter, Genevieve Alexander, G. Caleb Nair, Kavita TI Effect of Physician Payment Disclosure Laws on Prescribing SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Nair, Kavita] Univ Colorado, Dept Clin Pharm, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO 80045 USA. [Pham-Kanter, Genevieve] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. [Pham-Kanter, Genevieve] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Pham-Kanter, Genevieve] Univ Colorado, Dept Hlth Syst Management & Policy, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Pham-Kanter, Genevieve] Univ Colorado, Dept Econ, Denver, CO 80202 USA. [Alexander, G. Caleb] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RP Nair, K (reprint author), Univ Colorado, Dept Clin Pharm, Skaggs Sch Pharm & Pharmaceut Sci, Anschutz Med Campus,Mail Stop C238,12850 E Montvi, Aurora, CO 80045 USA. EM kavita.nair@ucdenver.edu OI Pham-Kanter, Genevieve/0000-0002-3044-7829 FU AHRQ HHS [R01 HS0189960]; NCRR NIH HHS [UL1 RR025758]; NHLBI NIH HHS [R01 HL 107345-01, R01 HL107345]; NICHD NIH HHS [P2C HD047879, T32 HD007163] NR 4 TC 14 Z9 14 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2012 VL 172 IS 10 BP 819 EP 821 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 948FK UT WOS:000304488800014 PM 22636826 ER PT J AU Grant, RW Wexler, DJ Ashburner, JM Hong, CS Atlas, SJ AF Grant, Richard W. Wexler, Deborah J. Ashburner, Jeffrey M. Hong, Clemens S. Atlas, Steven J. TI Characteristics of "Complex" Patients With Type 2 Diabetes Mellitus According to Their Primary Care Physicians SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Grant, Richard W.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Ashburner, Jeffrey M.; Hong, Clemens S.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Wexler, Deborah J.; Hong, Clemens S.; Atlas, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RP Grant, RW (reprint author), Kaiser Permanente No Calif, Div Res, 2101 Webster St, Oakland, CA 94612 USA. EM Richard.W.Grant@kp.org OI Grant, Richard/0000-0002-6164-8025 NR 4 TC 15 Z9 15 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2012 VL 172 IS 10 BP 821 EP 823 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 948FK UT WOS:000304488800015 PM 22636827 ER PT J AU Grady, D Katz, MH Berkowitz, SA AF Grady, Deborah Katz, Mitchell H. Berkowitz, Seth A. TI A Role for Opioids in Chronic Pain Management reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94115 USA. [Katz, Mitchell H.] Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2012 VL 172 IS 10 BP 824 EP 825 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 948FK UT WOS:000304488800019 ER PT J AU Gabbita, SP Srivastava, MK Eslami, P Johnson, MF Kobritz, NK Tweedie, D Greig, NH Zemlan, FP Sharma, SP Harris-White, ME AF Gabbita, S. Prasad Srivastava, Minu K. Eslami, Pirooz Johnson, Ming F. Kobritz, Naomi K. Tweedie, David Greig, Nigel H. Zemlan, Frank P. Sharma, Sherven P. Harris-White, Marni E. TI Early intervention with a small molecule inhibitor for tumor necrosis factor-alpha prevents cognitive deficits in a triple transgenic mouse model of Alzheimer's disease SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Alzheimer's disease; memory; neuroinflammation; thalidomide; thiothalidomide; tumor necrosis factor-alpha ID CENTRAL-NERVOUS-SYSTEM; BETA-AMYLOID STIMULATION; MARROW-DERIVED CELLS; BLOOD-BRAIN-BARRIER; TNF-ALPHA; NEURODEGENERATIVE DISEASES; PERISPINAL ETANERCEPT; SYNAPTIC PLASTICITY; HEMATOPOIETIC-CELLS; THERAPEUTIC TARGET AB Background: Chronic neuroinflammation is an important component of Alzheimer's disease and could contribute to neuronal dysfunction, injury and loss that lead to disease progression. Multiple clinical studies implicate tumor necrosis factor-alpha as an inflammatory mediator of neurodegeneration in patients with Alzheimer's because of elevated levels of this cytokine in the cerebrospinal fluid, hippocampus and cortex. Current Alzheimer's disease interventions are symptomatic treatments with limited efficacy that do not address etiology. Thus, a critical need exists for novel treatments directed towards modifying the pathophysiology and progression. Methods: To investigate the effect of early immune modulation on neuroinflammation and cognitive outcome, we treated triple transgenic Alzheimer's disease mice (harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes) with the small molecule tumor necrosis factor-alpha inhibitors, 3,6'-dithiothalidomide and thalidomide, beginning at four months of age. At this young age, mice do not exhibit plaque or tau pathology but do show mild intraneuronal amyloid beta protein staining and a robust increase in tumor necrosis factor-alpha. After 10 weeks of treatment, cognitive performance was assessed using radial arm maze and neuroinflammation was assessed using biochemical, stereological and flow cytometric endpoints. Results: 3,6'-dithiothalidomide reduced tumor necrosis factor-alpha mRNA and protein levels in the brain and improved working memory performance and the ratio of resting to reactive microglia in the hippocampus of triple transgenic mice. In comparison to non-transgenic controls, triple transgenic Alzheimer's disease mice had increased total numbers of infiltrating peripheral monomyelocytic/granulocytic leukocytes with enhanced intracytoplasmic tumor necrosis factor-alpha, which was reduced after treatment with 3,6'-dithiothalidomide. Conclusions: These results suggest that modulation of tumor necrosis factor-alpha with small molecule inhibitors is safe and effective with potential for the long-term prevention and treatment of Alzheimer's disease. C1 [Srivastava, Minu K.; Eslami, Pirooz; Johnson, Ming F.; Kobritz, Naomi K.; Sharma, Sherven P.; Harris-White, Marni E.] Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Srivastava, Minu K.; Eslami, Pirooz; Johnson, Ming F.; Kobritz, Naomi K.; Sharma, Sherven P.; Harris-White, Marni E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Gabbita, S. Prasad; Zemlan, Frank P.] P2D Biosci, Cincinnati, OH 45242 USA. [Tweedie, David; Greig, Nigel H.] NIA, NIH, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Harris-White, ME (reprint author), Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 151, Los Angeles, CA 90073 USA. EM marni@ucla.edu FU Veterans Administration; Michael J. Fox Foundation; Alzheimer's Drug Discovery Foundation; Intramural Research Program of NIA, NIH FX The authors would like to thank Dr. Russell Brown at Eastern Tennessee State University for assistance with the design and analysis of the Radial Arm Maze experiments, Dr. Louis Hersh at the University of Kentucky for providing breeding pairs of 3 x Tg mice and Dr. Kenneth Hensley at the University of Toledo for assistance with data interpretation and critical scientific review of the manuscript. This work was supported by Veterans Administration Merit Funding (MEHW and SPS), Michael J. Fox Foundation (SPG), Alzheimer's Drug Discovery Foundation (MEHW and SPG) and the Intramural Research Program of NIA, NIH (DT and NHG). NR 81 TC 26 Z9 27 U1 2 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD MAY 25 PY 2012 VL 9 AR 99 DI 10.1186/1742-2094-9-99 PG 16 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 976PV UT WOS:000306597700001 PM 22632257 ER PT J AU Sung, RJ Zhang, M Qi, Y Verdine, GL AF Sung, Rou-Jia Zhang, Michael Qi, Yan Verdine, Gregory L. TI Sequence-dependent Structural Variation in DNA Undergoing Intrahelical Inspection by the DNA glycosylase MutM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPAIR ENZYME; CRYSTAL-STRUCTURE; BASE-EXCISION; LESION RECOGNITION; ESCHERICHIA-COLI; DAMAGED DNA; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; MUTATIONAL HOTSPOT; PROTEIN-STRUCTURE; ABASIC SITE AB MutM, a bacterial DNA-glycosylase, plays a critical role in maintaining genome integrity by catalyzing glycosidic bond cleavage of 8-oxoguanine (oxoG) lesions to initiate base excision DNA repair. The task faced by MutM of locating rare oxoG residues embedded in an overwhelming excess of undamaged bases is especially challenging given the close structural similarity between oxoG and its normal progenitor, guanine (G). MutM actively interrogates the DNA to detect the presence of an intrahelical, fully base-paired oxoG, whereupon the enzyme promotes extrusion of the target nucleobase from the DNA duplex and insertion into the extrahelical active site. Recent structural studies have begun to provide the first glimpse into the protein DNA interactions that enable MutM to distinguish an intrahelical oxoG from G; however, these initial studies left open the important question of how MutM can recognize oxoG residues embedded in 16 different neighboring sequence contexts (considering only the 5'- and 3'-neighboring base pairs). In this study we set out to understand the manner and extent to which intrahelical lesion recognition varies as a function of the 5'-neighbor. Here we report a comprehensive, systematic structural analysis of the effect of the 5'-neighboring base pair on recognition of an intrahelical oxoG lesion. These structures reveal that MutM imposes the same extrusion-prone ("extrudogenic") backbone conformation on the oxoG lesion irrespective of its 5'-neighbor while leaving the rest of the DNA relatively free to adjust to the particular demands of individual sequences. C1 [Sung, Rou-Jia; Verdine, Gregory L.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. [Zhang, Michael; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Chem Biol Initiat, Boston, MA 02115 USA. [Qi, Yan] Harvard Univ, Sch Med, Grad Program Biophys, Boston, MA 02115 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), 12 Oxford St, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu FU National Institutes of Health [GM044853, CA100742]; Harvard College Research Program; National Science Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants GM044853 and CA100742.; Supported by a grant by the Harvard College Research Program.; Supported by a predoctoral fellowship from the National Science Foundation. NR 50 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2012 VL 287 IS 22 BP 18044 EP 18054 DI 10.1074/jbc.M111.313635 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974EC UT WOS:000306411600014 PM 22465958 ER PT J AU Gude, L Berkovitch, SS Santos, WL Kutchukian, PS Pawloski, AR Kuimelis, R McGall, G Verdine, GL AF Gude, Lourdes Berkovitch, Shaunna S. Santos, Webster L. Kutchukian, Peter S. Pawloski, Adam R. Kuimelis, Robert McGall, Glenn Verdine, Gregory L. TI Mapping Targetable Sites on Human Telomerase RNA Pseudoknot/Template Domain Using 2 '-OMe RNA-interacting Polynucleotide (RIPtide) Microarrays SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SECONDARY STRUCTURE; COMPLEMENTARY OLIGONUCLEOTIDES; REVERSE-TRANSCRIPTASE; NUCLEIC-ACIDS; HUMAN-CELLS; IN-VIVO; INHIBITION; ARRAYS; PROTEIN; CANCER AB Most cellular RNAs engage in intrastrand base-pairing that gives rise to complex three-dimensional folds. This self-pairing presents an impediment toward binding of the RNA by nucleic acid-based ligands. An important step in the discovery of RNA-targeting ligands is therefore to identify those regions in a folded RNA that are accessible toward the nucleic acid-based ligand. Because the folding of RNA targets can involve interactions between nonadjacent regions and employ both Watson-Crick and non-Watson-Crick base-pairing, screening of candidate binder ensembles is typically necessary. Microarray-based screening approaches have shown great promise in this regard and have suggested that achieving complete sequence coverage would be a valuable attribute of a next generation system. Here, we report a custom microarray displaying a library of RNA-interacting polynucleotides comprising all possible 2'-OMe RNA sequences from 4- to 8-nucleotides in length. We demonstrate the utility of this array in identifying RNA-interacting polynucleotides that bind tightly and specifically to the highly conserved, functionally essential template/pseudoknot domain of human telomerase RNA and that inhibit telomerase function in vitro. C1 [Gude, Lourdes; Kutchukian, Peter S.; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Berkovitch, Shaunna S.; Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Pawloski, Adam R.; Kuimelis, Robert; McGall, Glenn] Affymetrix Inc, Santa Clara, CA 95051 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), 12 Oxford St, Cambridge, MA 02138 USA. EM Gregory_verdine@harvard.edu RI Gude, Lourdes/E-5860-2012; Kutchukian, Peter/A-9826-2016; OI Gude, Lourdes/0000-0002-0220-3755; Kutchukian, Peter/0000-0002-5684-1971; Santos, Webster/0000-0002-4731-8548 FU National Institutes of Health [R01 GM044853]; NRSA [F32 GM067380]; High-Tech Fund of the Dana-Farber Cancer Institute; Spanish Ministerio de Educacion y Ciencia; National Science Foundation; [T32 GM007598] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 GM044853 (to G. L. V.), Grant F32 GM067380 from NRSA (to W. L. S.), and Training Grant T32 GM007598 (to S. S. B.). This work was also supported by the High-Tech Fund of the Dana-Farber Cancer Institute, postdoctoral fellowships from the Spanish Ministerio de Educacion y Ciencia (to L. G.), and a National Science Foundation predoctoral fellowship (to P. S. K.). Affymetrix Inc. is a for-profit entity. G. L. V. is a shareholder, consultant to, and corporate officer of Ontorii, Inc., which has secured an option from Harvard University to commercialize the RIPtide technology. NR 55 TC 8 Z9 10 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2012 VL 287 IS 22 BP 18843 EP 18853 DI 10.1074/jbc.M111.316596 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974EC UT WOS:000306411600092 PM 22451672 ER PT J AU Ferrandiz, N Caraballo, JM Garcia-Gutierrez, L Devgan, V Rodriguez-Paredes, M Lafita, MC Bretones, G Quintanilla, A Munoz-Alonso, MJ Blanco, R Reyes, JC Agell, N Delgado, MD Dotto, GP Leon, J AF Ferrandiz, Nuria Caraballo, Juan M. Garcia-Gutierrez, Lucia Devgan, Vikram Rodriguez-Paredes, Manuel Carmen Lafita, M. Bretones, Gabriel Quintanilla, Andrea Jose Munoz-Alonso, M. Blanco, Rosa Reyes, Jose C. Agell, Neus Dolores Delgado, M. Dotto, G. Paolo Leon, Javier TI p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes SO PLOS ONE LA English DT Article ID CELL-CYCLE INHIBITION; TUMOR SUPPRESSION; DNA-REPLICATION; UP-REGULATION; P21(WAF1/CIP1); DIFFERENTIATION; EXPRESSION; P21(CIP1/WAF1); ARREST; ENDOREDUPLICATION AB It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes. C1 [Ferrandiz, Nuria; Caraballo, Juan M.; Garcia-Gutierrez, Lucia; Carmen Lafita, M.; Bretones, Gabriel; Quintanilla, Andrea; Jose Munoz-Alonso, M.; Blanco, Rosa; Dolores Delgado, M.; Leon, Javier] Univ Cantabria, CSIC, SODERCAN, Dept Biol Mol,Inst Biomed & Biotecnol Cantabria I, E-39005 Santander, Spain. [Devgan, Vikram; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Rodriguez-Paredes, Manuel; Reyes, Jose C.] CSIC, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, E-41080 Seville, Spain. [Jose Munoz-Alonso, M.] CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain. [Agell, Neus] Univ Barcelona, Dept Biol Cellular Immunol & Neurociencies, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. RP Ferrandiz, N (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Fac Med, Hammersmith Hosp Campus, London, England. EM leonj@unican.es RI Reyes, Jose/K-3699-2014; Agell, Neus/E-9640-2016; OI Reyes, Jose/0000-0002-8042-5142; Agell, Neus/0000-0002-1205-6074 FU Spanish Ministerio de Ciencia e Innovacion (MICINN) [SAF08-01581, ISCIII-RETIC RD06/0020/0017]; MICINN [BFU2008-00238, CSD2006-00049]; Junta de Andalucia [P06-CVI-4844]; postdoctoral fellowship of the University of Cantabria; [FIS 08/0829] FX This study was supported by grants SAF08-01581 and ISCIII-RETIC RD06/0020/0017 from the Spanish Ministerio de Ciencia e Innovacion (MICINN) to JL; FIS 08/0829 to MDD; BFU2008-00238 and CSD2006-00049 from MICINN, and P06-CVI-4844 from Junta de Andalucia to JCR. NF was the recipient of a postdoctoral fellowship of the University of Cantabria. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript. NR 48 TC 14 Z9 14 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 25 PY 2012 VL 7 IS 5 AR e37759 DI 10.1371/journal.pone.0037759 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UY UT WOS:000305342300103 PM 22662213 ER PT J AU Kostopoulou, F Gkretsi, V Malizos, KN Iliopoulos, D Oikonomou, P Poultsides, L Tsezou, A AF Kostopoulou, Fotini Gkretsi, Vasiliki Malizos, Konstantinos N. Iliopoulos, Dimitrios Oikonomou, Pagona Poultsides, Lazaros Tsezou, Aspasia TI Central Role of SREBP-2 in the Pathogenesis of Osteoarthritis SO PLOS ONE LA English DT Article ID STEROL-REGULATORY ELEMENT; BINDING PROTEIN (SREBP)-2; LEUCINE ZIPPER PROTEIN; EXPRESSION; GENE; TRANSCRIPTION; CHONDROCYTES; CHOLESTEROL; IDENTIFICATION; POPULATION AB Background: Recent studies have implied that osteoarthritis (OA) is a metabolic disease linked to deregulation of genes involved in lipid metabolism and cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are transcription factors regulating lipid metabolism with so far no association with OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role in cholesterol homeostasis, is crucially involved in OA pathogenesis and to identify possible mechanisms of action. Methodology/Principal Findings: We performed a genetic association analysis using a cohort of 1,410 Greek OA patients and healthy controls and found significant association between single nucleotide polymorphism (SNP) 1784G>C in SREBP-2 gene and OA development. Moreover, the above SNP was functionally active, as normal chondrocytes' transfection with SREBP-2-G/C plasmid resulted in interleukin-1 beta and metalloproteinase-13 (MMP-13) upregulation. We also evaluated SREBP-2, its target gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho-phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and transforming growth factor-beta (TGF-beta) mRNA and protein expression levels in osteoarthritic and normal chondrocytes and found that they were all significantly elevated in OA chondrocytes. To test whether TGF-beta alone can induce SREBP-2, we treated normal chondrocytes with TGF-beta and found significant upregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13. We also showed that TGF-beta activated aggrecan (ACAN) in chondrocytes only through Smad3, which interacts with SREBP-2. Finally, we examined the effect of an integrin inhibitor, cyclo-RGDFV peptide, on osteoarthritic chondrocytes, and found that it resulted in significant upregulation of ACAN and downregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13 expression levels. Conclusions/Significance: We demonstrated, for the first time, the association of SREBP-2 with OA pathogenesis and provided evidence on the molecular mechanism involved. We suggest that TGF-beta induces SREBP-2 pathway activation through ITGAV and PI3K playing a key role in OA and that integrin blockage may be a potential molecular target for OA treatment. C1 [Kostopoulou, Fotini; Tsezou, Aspasia] Univ Thessaly, Dept Cytogenet & Mol Genet, Sch Med, Larisa, Greece. [Kostopoulou, Fotini; Gkretsi, Vasiliki; Malizos, Konstantinos N.; Oikonomou, Pagona; Tsezou, Aspasia] Ctr Res & Technol Thessaly, Inst Biomed Res & Technol, Larisa, Greece. [Malizos, Konstantinos N.; Poultsides, Lazaros] Univ Thessaly, Dept Orthopaed, Sch Med, Larisa, Greece. [Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Tsezou, Aspasia] Univ Thessaly, Dept Biol, Sch Med, Larisa, Greece. RP Kostopoulou, F (reprint author), Univ Thessaly, Dept Cytogenet & Mol Genet, Sch Med, Larisa, Greece. EM atsezou@med.uth.gr OI Gkretsi, Vasiliki/0000-0002-3671-4078 FU Hellenic Society of Orthopaedic Surgery and Traumatology FX The present study was financed by the Hellenic Society of Orthopaedic Surgery and Traumatology. No additional external funding was received. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 38 TC 21 Z9 23 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 25 PY 2012 VL 7 IS 5 AR e35753 DI 10.1371/journal.pone.0035753 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UY UT WOS:000305342300005 PM 22662110 ER PT J AU Makino, CL Wen, XH Michaud, NA Covington, HI DiBenedetto, E Hamm, HE Lem, J Caruso, G AF Makino, Clint L. Wen, Xiao-Hong Michaud, Norman A. Covington, Henry I. DiBenedetto, Emmanuele Hamm, Heidi E. Lem, Janis Caruso, Giovanni TI Rhodopsin Expression Level Affects Rod Outer Segment Morphology and Photoresponse Kinetics SO PLOS ONE LA English DT Article ID PHOTORECEPTOR MEMBRANE; LATERAL DIFFUSION; TRANSGENIC MICE; DISK MEMBRANES; FINE STRUCTURE; KNOCKOUT MICE; MOUSE RETINA; PHOTOTRANSDUCTION; ORGANIZATION; TRANSPORT AB Background: The retinal rod outer segment is a sensory cilium that is specialized for the conversion of light into an electrical signal. Within the cilium, up to several thousand membranous disks contain as many as a billion copies of rhodopsin for efficient photon capture. Disks are continually turned over, requiring the daily synthesis of a prodigious amount of rhodopsin. To promote axial diffusion in the aqueous cytoplasm, the disks have one or more incisures. Across vertebrates, the range of disk diameters spans an order of magnitude, and the number and length of the incisures vary considerably, but the mechanisms controlling disk architecture are not well understood. The finding that transgenic mice overexpressing rhodopsin have enlarged disks lacking an incisure prompted us to test whether lowered rhodopsin levels constrain disk assembly. Methodology/Principal Findings: The structure and function of rods from hemizygous rhodopsin knockout (R+/-) mice with decreased rhodopsin expression were analyzed by transmission electron microscopy and single cell recording. R+/- rods were structurally altered in three ways: disk shape changed from circular to elliptical, disk surface area decreased, and the single incisure lengthened to divide the disk into two sections. Photocurrent responses to flashes recovered more rapidly than normal. A spatially resolved model of phototransduction indicated that changes in the packing densities of rhodopsin and other transduction proteins were responsible. The decrease in aqueous outer segment volume and the lengthened incisure had only minor effects on photon response amplitude and kinetics. Conclusions/Significance: Rhodopsin availability limits disk assembly and outer segment girth in normal rods. The incisure may buffer the supply of structural proteins needed to form larger disks. Decreased rhodopsin level accelerated photoresponse kinetics by increasing the rates of molecular collisions on the membrane. Faster responses, together with fewer rhodopsins, combine to lower overall sensitivity of R+/- rods to light. C1 [Makino, Clint L.; Wen, Xiao-Hong; Michaud, Norman A.; Covington, Henry I.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [DiBenedetto, Emmanuele] Vanderbilt Univ, Dept Math, Nashville, TN USA. [Hamm, Heidi E.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Lem, Janis] Tufts Univ, Sch Med, Dept Ophthalmol, Program Genet,Program Neurosci,Program Cell Mol &, Boston, MA 02111 USA. [Caruso, Giovanni] CNR, Construct Technol Inst, Rome, Italy. RP Makino, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM cmakino@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU National Eye Institute [EY006062, EY011358, EY014104, EY12008]; National Institute of General Medical Sciences [GM068953]; National Science Foundation [DMS 0652385, DMS 0970008]; Lions of Massachusetts FX This work was supported by grants from the National Eye Institute (EY006062, EY011358, EY014104, EY12008), National Institute of General Medical Sciences (GM068953), National Science Foundation (DMS 0652385, DMS 0970008), and Lions of Massachusetts. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 15 Z9 15 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 25 PY 2012 VL 7 IS 5 AR e37832 DI 10.1371/journal.pone.0037832 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UY UT WOS:000305342300124 PM 22662234 ER PT J AU Mathalon, DH Ford, JM AF Mathalon, Daniel H. Ford, Judith M. TI Neurobiology of schizophrenia: search for the elusive correlation with symptoms SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE schizophrenia; positive symptoms; negative symptoms; neurobiology; correlation; reliability; validity; rating scales ID TRANSCRANIAL MAGNETIC STIMULATION; PSYCHIATRIC RATING-SCALE; HEALTHY-VOLUNTEERS; WORKING-MEMORY; KETAMINE; DYSFUNCTION; NEGATIVITY; ANTAGONIST; PSYCHOSIS; DEFICITS AB In the last half-century, human neuro science methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation-causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships. C1 [Mathalon, Daniel H.; Ford, Judith M.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU CSRD VA [I01 CX000497]; NIMH NIH HHS [R01 MH076989] NR 43 TC 16 Z9 16 U1 2 U2 14 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAY 25 PY 2012 VL 6 AR 136 DI 10.3389/fnhum.2012.00136 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 953HT UT WOS:000304858500001 PM 22654745 ER PT J AU Mantegazza, AR Guttentag, SH El-Benna, J Sasai, M Iwasaki, A Shen, H Laufer, TM Marks, MS AF Mantegazza, Adriana R. Guttentag, Susan H. El-Benna, Jamel Sasai, Miwa Iwasaki, Akiko Shen, Hao Laufer, Terri M. Marks, Michael S. TI Adaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4(+) T Cells SO IMMUNITY LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; MHC CLASS-II; AP-3 ADAPTER; CROSS-PRESENTATION; BETA-3A SUBUNIT; SORTING SIGNALS; IMMUNE-RESPONSE; SYNDROME TYPE-2; TRAFFICKING; MUTATIONS AB Effective major histocompatibility complex-II (MHC-II) antigen presentation from phagocytosed particles requires phagosome-intrinsic Toll-like receptor (TLR) signaling, but the molecular mechanisms underlying TLR delivery to phagosomes and how signaling regulates antigen presentation are incompletely understood. We show a requirement in dendritic cells (DCs) for adaptor protein-3 (AP-3) in efficient TLR recruitment to phagosomes and MHC-II presentation of antigens internalized by phagocytosis but not receptor-mediated endocytosis. DCs from AP-3-deficient pearl mice elicited impaired CD4(+) T cell activation and Th1 effector cell function to particulate antigen in vitro and to recombinant Listeria monocytogenes infection in vivo. Whereas phagolysosome maturation and peptide:MHC-II complex assembly proceeded normally in pearl DCs, peptide:MHC-II export to the cell surface was impeded. This correlated with reduced TLR4 recruitment and proinflammatory signaling from phagosomes by particulate TLR ligands. We propose that AP-3-dependent TLR delivery from endosomes to phagosomes and subsequent signaling mobilize peptide:MHC-II export from intracellular stores. C1 [Mantegazza, Adriana R.; Marks, Michael S.] Univ Penn, Perelman Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. [Mantegazza, Adriana R.; Marks, Michael S.] Univ Penn, Perelman Sch Med, Dept Lab Med, Philadelphia, PA 19104 USA. [Mantegazza, Adriana R.; Marks, Michael S.] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. [Shen, Hao] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Guttentag, Susan H.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [El-Benna, Jamel] Univ Paris 07, INSERM, U773, Fac Med, F-75018 Paris, France. [Sasai, Miwa; Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Marks, MS (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. EM marksm@mail.med.upenn.edu RI Guttentag, Susan/D-8705-2013; OI Guttentag, Susan/0000-0003-4420-5879; Marks, Michael/0000-0001-7435-7262 FU National Institutes of Health [R01 EY015625, R21 AI092398, R21 AI079724, R01 AI081884, R01 AI064705]; University Research Foundation from the University of Pennsylvania; HPS Network; United States Veterans Administration FX We thank R. Steinman, M. Pepper Pew, M. Jenkins, A. Rudensky, J. Liboon, S. Chatterjee, A. Fisher, S. Ross, S. Akira, P. Oliver, L. Eisenlohr, M. Chou, and C. Lopez for generous gifts of reagents; A. Stout, P. Zhang, S. Leach, A. Sitaram, and C. Lopez Haber for technical assistance; and the Amigorena laboratory for experimental protocols. This work was supported by National Institutes of Health grants R01 EY015625 (to M.S.M.), R21 AI092398 (to A.R.M. and M.S.M.), R21 AI079724 (to H.S.), and R01 AI081884 and R01 AI064705 (to A.I); a University Research Foundation grant from the University of Pennsylvania (to M.S.M.); Donna and Richard Appel and the HPS Network (to S.H.G.); and a research grant from the United States Veterans Administration (to T.M.L.). NR 57 TC 25 Z9 26 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY 25 PY 2012 VL 36 IS 5 BP 782 EP 794 DI 10.1016/j.immuni.2012.02.018 PG 13 WC Immunology SC Immunology GA 954VL UT WOS:000304976000012 PM 22560444 ER PT J AU Nik-Zainal, S Alexandrov, LB Wedge, DC Van Loo, P Greenman, CD Raine, K Jones, D Hinton, J Marshall, J Stebbings, LA Menzies, A Martin, S Leung, K Chen, L Leroy, C Ramakrishna, M Rance, R Lau, KW Mudie, LJ Varela, I McBride, DJ Bignell, GR Cooke, SL Shlien, A Gamble, J Whitmore, I Maddison, M Tarpey, PS Davies, HR Papaemmanuil, E Stephens, PJ McLaren, S Butler, AP Teague, JW Jonsson, G Garber, JE Silver, D Miron, P Fatima, A Boyault, S Langerod, A Tutt, A Martens, JWM Aparicio, SAJR Borg, A Salomon, AV Thomas, G Borresen-Dale, AL Richardson, AL Neuberger, MS Futreal, PA Campbell, PJ Stratton, MR AF Nik-Zainal, Serena Alexandrov, Ludmil B. Wedge, David C. Van Loo, Peter Greenman, Christopher D. Raine, Keiran Jones, David Hinton, Jonathan Marshall, John Stebbings, Lucy A. Menzies, Andrew Martin, Sancha Leung, Kenric Chen, Lina Leroy, Catherine Ramakrishna, Manasa Rance, Richard Lau, King Wai Mudie, Laura J. Varela, Ignacio McBride, David J. Bignell, Graham R. Cooke, Susanna L. Shlien, Adam Gamble, John Whitmore, Ian Maddison, Mark Tarpey, Patrick S. Davies, Helen R. Papaemmanuil, Elli Stephens, Philip J. McLaren, Stuart Butler, Adam P. Teague, Jon W. Jonsson, Goran Garber, Judy E. Silver, Daniel Miron, Penelope Fatima, Aquila Boyault, Sandrine Langerod, Anita Tutt, Andrew Martens, John W. M. Aparicio, Samuel A. J. R. Borg, Ake Salomon, Anne Vincent Thomas, Gilles Borresen-Dale, Anne-Lise Richardson, Andrea L. Neuberger, Michael S. Futreal, P. Andrew Campbell, Peter J. Stratton, Michael R. CA Int Canc Genome Consortium TI Mutational Processes Molding the Genomes of 21 Breast Cancers SO CELL LA English DT Article ID NONNEGATIVE MATRIX FACTORIZATION; RNA-EDITING PROTEIN; DNA-DAMAGE; SOMATIC HYPERMUTATION; HEPATOCELLULAR-CARCINOMA; TOBACCO-SMOKE; P53 MUTATIONS; GENE; PATTERNS; TUMORS AB All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed. C1 [Nik-Zainal, Serena; Alexandrov, Ludmil B.; Wedge, David C.; Van Loo, Peter; Greenman, Christopher D.; Raine, Keiran; Jones, David; Hinton, Jonathan; Marshall, John; Stebbings, Lucy A.; Menzies, Andrew; Martin, Sancha; Leung, Kenric; Chen, Lina; Leroy, Catherine; Ramakrishna, Manasa; Rance, Richard; Lau, King Wai; Mudie, Laura J.; Varela, Ignacio; McBride, David J.; Bignell, Graham R.; Cooke, Susanna L.; Shlien, Adam; Gamble, John; Whitmore, Ian; Maddison, Mark; Tarpey, Patrick S.; Davies, Helen R.; Papaemmanuil, Elli; Stephens, Philip J.; McLaren, Stuart; Butler, Adam P.; Teague, Jon W.; Futreal, P. Andrew; Campbell, Peter J.; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Van Loo, Peter] VIB, Ctr Biol Dis, B-3000 Louvain, Belgium. [Van Loo, Peter] Katholieke Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium. [Greenman, Christopher D.] Univ E Anglia, Dept Comp, Norwich NR4 7TJ, Norfolk, England. [Greenman, Christopher D.] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England. [Aparicio, Samuel A. J. R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada. [Garber, Judy E.; Silver, Daniel; Miron, Penelope; Fatima, Aquila; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Boyault, Sandrine; Thomas, Gilles] Ctr Leon Berard, INCa Synergie, Fac Med, Lyon 08, France. [Langerod, Anita; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Tutt, Andrew] Kings Coll London, Breakthrough Breast Canc Res Unit, London SE1 9RT, England. [Martens, John W. M.] Erasmus MC, Dept Med Oncol, NL-3000 CA Rotterdam, Netherlands. [Aparicio, Samuel A. J. R.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. [Jonsson, Goran; Borg, Ake] Lund Univ, Dept Oncol, SE-22184 Lund, Sweden. [Salomon, Anne Vincent] Inst Curie, Dept Pathol, F-75248 Paris 05, France. [Salomon, Anne Vincent] INSERM, U830, F-75248 Paris 05, France. [Borresen-Dale, Anne-Lise] Univ Oslo, KG Jebsen Ctr Breast Canc Res, Inst Clin Med, Fac Med, N-0310 Oslo, Norway. [Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Neuberger, Michael S.] MRC Lab Mol Biol, Cambridge CB2 0QH, England. [Campbell, Peter J.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England. [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. RP Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. EM mrs@sanger.ac.uk RI Van Loo, Peter/A-3287-2012; Jonsson, Goran/D-1212-2014; Alexandrov, Ludmil/B-6582-2014; Varela, Ignacio/G-1699-2016; OI Alexandrov, Ludmil/0000-0003-3596-4515; Varela, Ignacio/0000-0002-0969-506X; Van Loo, Peter/0000-0003-0292-1949; Wedge, David/0000-0002-7572-3196; Martin, Sancha/0000-0001-6213-5259 FU Wellcome Trust [098051]; Breakthrough Breast Cancer Research [ICGC 08/09]; Wellcome Trust Clinical Research; Wellcome Trust Senior Clinical Research [WT088340MA]; Research Foundation - Flanders [FWO]; National Research Council Canada; EMBO; International Human Frontier Science Program Organization; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research; Norwegian Research Council; The Norwegian Cancer Society; The Radium Hospital Foundation; Health Region South-East; European Community [242006]; Breast Cancer Somatic Genetics Study [BASIS]; Wellcome Trust Sanger Institute; Breakthrough Breast Cancer Unit; ICGC Breast Cancer Working Group; Oslo University Hospital; United States National Cancer Institute Specialized Program Of Research Excellence [CA089393]; Centre for Translational Genomics (CTAG); Department of Health via NIHR comprehensive Biomedical Research Centre; NHS Foundation Trust, King's College London; King's College Hospital NHS Foundation Trust FX This work was supported by the Wellcome Trust (grant reference 098051) and Breakthrough Breast Cancer Research (ICGC 08/09). Individual support: S.N.Z. (Wellcome Trust Clinical Research Training Fellow); P.J.C. (Wellcome Trust Senior Clinical Research Fellow grant reference WT088340MA); P.V.L. (Research Foundation - Flanders [FWO]); A.S. (National Research Council Canada [HL Holmes Award] and EMBO); I.V. (International Human Frontier Science Program Organization); J.W.M.M. (Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research); A.L.B.D. and A.L. (Norwegian Research Council, The Norwegian Cancer Society, The Radium Hospital Foundation and Health Region South-East); S.M (European Community's Seventh Framework Programme [FP7/2010-2014] grant reference 242006 Breast Cancer Somatic Genetics Study [BASIS]). We thank Nancy Miller for her activities related to the curation and collection of the clinical data associated with this study. We acknowledge the Core Sequencing Facility and IT groups of the Wellcome Trust Sanger Institute, the Breakthrough Breast Cancer Unit, members of the ICGC Breast Cancer Working Group, the OSBREAC Consortium of Oslo University Hospital, the United States National Cancer Institute Specialized Program Of Research Excellence (grant reference CA089393) and Dr. Peter Watson of the BCCA Tumour Tissue Repository and the Centre for Translational Genomics (CTAG). The authors acknowledge financial support from the Department of Health via NIHR comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, King's College London, and King's College Hospital NHS Foundation Trust. We thank George Vassiliou for pointing us to the term "kataegis.'' J.E.G. is a consultant for Generation Health. NR 60 TC 545 Z9 553 U1 9 U2 85 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 25 PY 2012 VL 149 IS 5 BP 979 EP 993 DI 10.1016/j.cell.2012.04.024 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 947TN UT WOS:000304453900006 PM 22608084 ER PT J AU Nik-Zainal, S Van Loo, P Wedge, DC Alexandrov, LB Greenman, CD Lau, KW Raine, K Jones, D Marshall, J Ramakrishna, M Shlien, A Cooke, SL Hinton, J Menzies, A Stebbings, LA Leroy, C Jia, MM Rance, R Mudie, LJ Gamble, SJ Stephens, PJ McLaren, S Tarpey, PS Papaemmanuil, E Davies, HR Varela, I McBride, DJ Bignell, GR Leung, K Butler, AP Teague, JW Martin, S Jonsson, G Mariani, O Boyault, S Miron, P Fatima, A Langerod, A Aparicio, SAJR Tutt, A Sieuwerts, AM Borg, A Thomas, G Salomon, AV Richardson, AL Borresen-Dale, AL Futreal, PA Stratton, MR Campbell, PJ AF Nik-Zainal, Serena Van Loo, Peter Wedge, David C. Alexandrov, Ludmil B. Greenman, Christopher D. Lau, King Wai Raine, Keiran Jones, David Marshall, John Ramakrishna, Manasa Shlien, Adam Cooke, Susanna L. Hinton, Jonathan Menzies, Andrew Stebbings, Lucy A. Leroy, Catherine Jia, Mingming Rance, Richard Mudie, Laura J. Gamble, Stephen J. Stephens, Philip J. McLaren, Stuart Tarpey, Patrick S. Papaemmanuil, Elli Davies, Helen R. Varela, Ignacio McBride, David J. Bignell, Graham R. Leung, Kenric Butler, Adam P. Teague, Jon W. Martin, Sancha Joensson, Goran Mariani, Odette Boyault, Sandrine Miron, Penelope Fatima, Aquila Langerod, Anita Aparicio, Samuel A. J. R. Tutt, Andrew Sieuwerts, Anieta M. Borg, Ake Thomas, Gilles Salomon, Anne Vincent Richardson, Andrea L. Borresen-Dale, Anne-Lise Futreal, P. Andrew Stratton, Michael R. Campbell, Peter J. CA Int Canc Genome Consortium TI The Life History of 21 Breast Cancers SO CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GENOMIC REARRANGEMENT; PANCREATIC-CANCER; EVOLUTION; MUTATIONS; PATTERNS; INSTABILITY; METASTASIS; SIGNATURES; RESOLUTION AB Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis. C1 [Nik-Zainal, Serena; Van Loo, Peter; Wedge, David C.; Alexandrov, Ludmil B.; Greenman, Christopher D.; Lau, King Wai; Raine, Keiran; Jones, David; Marshall, John; Ramakrishna, Manasa; Shlien, Adam; Cooke, Susanna L.; Hinton, Jonathan; Menzies, Andrew; Stebbings, Lucy A.; Leroy, Catherine; Jia, Mingming; Rance, Richard; Mudie, Laura J.; Gamble, Stephen J.; Stephens, Philip J.; McLaren, Stuart; Tarpey, Patrick S.; Papaemmanuil, Elli; Davies, Helen R.; Varela, Ignacio; McBride, David J.; Bignell, Graham R.; Leung, Kenric; Butler, Adam P.; Teague, Jon W.; Martin, Sancha; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Van Loo, Peter] VIB, Ctr Biol Dis, B-3000 Louvain, Belgium. [Van Loo, Peter] Katholieke Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium. [Greenman, Christopher D.] Univ E Anglia, Dept Comp, Norwich NR4 7TJ, Norfolk, England. [Greenman, Christopher D.] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England. [Joensson, Goran; Tutt, Andrew] Kings Coll London, Breakthrough Breast Canc Res Unit, London SE1 9RT, England. [Mariani, Odette; Salomon, Anne Vincent] Inst Curie, Dept Tumor Biol, F-75248 Paris 05, France. [Boyault, Sandrine; Thomas, Gilles] Univ Lyon 1, Ctr Leon Berard, INCa Synergie, Lyon 08, France. [Miron, Penelope; Fatima, Aquila; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Langerod, Anita; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Aparicio, Samuel A. J. R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada. [Aparicio, Samuel A. J. R.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. [Sieuwerts, Anieta M.] Erasmus MC, NL-3000 CA Rotterdam, Netherlands. [Borg, Ake] Lund Univ, Dept Oncol, SE-22184 Lund, Sweden. [Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway. [Campbell, Peter J.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England. [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England. RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. EM pc8@sanger.ac.uk RI Van Loo, Peter/A-3287-2012; Gamble, Stephen/D-1417-2011; Jonsson, Goran/D-1212-2014; Alexandrov, Ludmil/B-6582-2014; Varela, Ignacio/G-1699-2016 OI Van Loo, Peter/0000-0003-0292-1949; Gamble, Stephen/0000-0002-0867-3723; Wedge, David/0000-0002-7572-3196; Martin, Sancha/0000-0001-6213-5259; Alexandrov, Ludmil/0000-0003-3596-4515; Varela, Ignacio/0000-0002-0969-506X FU Wellcome Trust [098051]; Breakthrough Breast Cancer Research [ICGC 08/09]; National Research Council Canada; EMBO; International Human Frontier Science Program Organization; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Norwegian Research Council; Norwegian Cancer Society; Radium Hospital Foundation; Health Region South-East; European Community [242006]; National Cancer Institute Specialized Program Of Research Excellence [CA089393]; Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre; St Thomas' NHS Foundation Trust FX This work was supported by the Wellcome Trust (grant reference 098051) and Breakthrough Breast Cancer Research (ICGC 08/09). S. N.-Z. is a Wellcome Trust Clinical Research Training Fellow. P.J.C. is a Wellcome Trust Senior Clinical Research Fellow (WT088340MA). P.V.L. is a postdoctoral researcher of the Research Foundation-Flanders. A.S. is supported by the HL Holmes Award from the National Research Council Canada and a Fellowship from EMBO. I.V. is supported by a fellowship from the International Human Frontier Science Program Organization. J.W.M.M. is funded in part by a research grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO). A.-L.B.-D. and A.L. are funded by the Norwegian Research Council, Norwegian Cancer Society, Radium Hospital Foundation and Health Region South-East. S. M. is funded by the BASIS project through the European Community's FP7/2010-2014 under grant agreement 242006. We acknowledge the Core Sequencing Facility and IT groups of the Wellcome Trust Sanger Institute, support for samples, sample banking, and processing from the Breakthrough Breast Cancer Unit, members of the ICGC Breast Cancer Working Group, the Pathology Review subgroup of the Breast Cancer Working Group, the OSBREAC Consortium of The Oslo University Hospital and the National Cancer Institute Specialized Program Of Research Excellence (grant reference CA089393). We also acknowledge Dr. Peter Watson, the BCCA Tumour Tissue Repository, and the Centre for Translational Genomics. The authors acknowledge financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust. NR 34 TC 450 Z9 456 U1 2 U2 71 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 25 PY 2012 VL 149 IS 5 DI 10.1016/j.cell.2012.04.023 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 947TN UT WOS:000304453900007 PM 22608083 ER PT J AU Jain, M Nilsson, R Sharma, S Madhusudhan, N Kitami, T Souza, AL Kafri, R Kirschner, MW Clish, CB Mootha, VK AF Jain, Mohit Nilsson, Roland Sharma, Sonia Madhusudhan, Nikhil Kitami, Toshimori Souza, Amanda L. Kafri, Ran Kirschner, Marc W. Clish, Clary B. Mootha, Vamsi K. TI Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation SO SCIENCE LA English DT Article ID ANTICANCER DRUG SCREEN; ONE-CARBON METABOLISM; BREAST-CANCER; SERINE HYDROXYMETHYLTRANSFERASE; EXPRESSION SIGNATURE; DEPENDENCE; SURVIVAL; MUTANTS; PATHWAY; NMR AB Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release ( CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation. C1 [Jain, Mohit; Nilsson, Roland; Madhusudhan, Nikhil; Kitami, Toshimori; Souza, Amanda L.; Clish, Clary B.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Jain, Mohit; Nilsson, Roland; Madhusudhan, Nikhil; Kitami, Toshimori; Kafri, Ran; Kirschner, Marc W.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Jain, Mohit; Nilsson, Roland; Madhusudhan, Nikhil; Kitami, Toshimori; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Jain, Mohit; Nilsson, Roland; Madhusudhan, Nikhil; Kitami, Toshimori; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jain, Mohit] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Nilsson, Roland] Karolinska Inst, Dept Med, Unit Computat Med, S-17176 Stockholm, Sweden. [Sharma, Sonia] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. RP Mootha, VK (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM vamsi@hms.harvard.edu FU NIH [K08HL107451, R01DK081457]; Knut & Alice Wallenberg Foundation; Stockholm County (SLL) [01626-2009]; Leukemia & Lymphoma Society FX We thank T. R. Golub, O. Shaham, S. B. Vafai, and L. Strittmatter for scientific discussions and feedback; X. Cao for assistance with glucose and lactate measurements; the Broad Institute RNAi Platform for shRNA reagents; D. Gomez-Cabrero for assistance with multidimensional scaling; A. Ploner and P. Dickman for assistance with survival analysis; W. C. Kopp, S. L. Holbeck, K. Gill, and P. Sellers of the Developmental Therapeutics Program, National Cancer Institute, for reagents and assistance with cell culture; and T. Hasaka of the Broad Institute for assistance with imaging studies. Supported by NIH grant K08HL107451 (M.J.), a postdoctoral scholarship from the Knut & Alice Wallenberg Foundation and Stockholm County (SLL) grant 01626-2009 (R.N.), a Special Fellow award from the Leukemia & Lymphoma Society (S. S.), and NIH grant R01DK081457 and a gift from the Nestle Research Center (V. K. M.). The full metabolite CORE profiling data set is available in the supplementary materials as well as through the NCI Molecular Targets data repository (http://dtp.nci.nih.gov/mtargets/download.html). M.J. and R.N. conceived and performed all experiments, collected and analyzed experimental data, and prepared the manuscript. S. S. assisted with cell culture, RNAi, and T lymphocyte experiments. N.M. and T. K. assisted with cell culture and imaging-based experiments. A. L. S. and C. B. C. performed LC-MS/MS profiling experiments and provided experimental feedback. R. K. and M. W. K. performed cell cycle studies. V. K. M. conceived all experiments, reviewed all experimental data, and prepared the manuscript. All authors have discussed the results and reviewed the manuscript. All authors declare no competing financial interests. NR 29 TC 367 Z9 383 U1 27 U2 169 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 25 PY 2012 VL 336 IS 6084 BP 1040 EP 1044 DI 10.1126/science.1218595 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 947DK UT WOS:000304406800047 PM 22628656 ER PT J AU Ma, TZ Su, ZJ Chen, L Liu, SY Zhu, NX Wen, LF Yuan, Y Lv, LL Chen, XC Huang, JM Chen, HB AF Ma, Tianzhong Su, Zhongjing Chen, Ling Liu, Shuyan Zhu, Ningxia Wen, Lifeng Yuan, Yan Lv, Leili Chen, Xiancai Huang, Jianmin Chen, Haibin TI Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2 SO PLOS ONE LA English DT Article ID HEPATOCELLULAR-CARCINOMA; CERVICAL-CANCER; LIVER; TRANSFORMATION; INFECTION; APOPTOSIS; BIOLOGY; PROTEIN; HPV-18; HBV AB Background and Objectives: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study. C1 [Ma, Tianzhong; Su, Zhongjing; Liu, Shuyan; Zhu, Ningxia; Wen, Lifeng; Yuan, Yan; Lv, Leili; Chen, Xiancai; Chen, Haibin] Shantou Univ, Dept Histol & Embryol, Coll Med, Shantou, Guangdong, Peoples R China. [Chen, Ling] Shantou Univ, Dept Biochem & Mol Biol, Coll Med, Shantou, Guangdong, Peoples R China. [Huang, Jianmin] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Jianmin] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Ma, TZ (reprint author), Shantou Univ, Dept Histol & Embryol, Coll Med, Shantou, Guangdong, Peoples R China. EM chenhb@stu.edu.cn FU Natural Science Foundation of Guangdong Province, China [10151503102000034]; Research Foundation of Shantou University Medical College [LC0401] FX This study was supported by Natural Science Foundation of Guangdong Province, China (Grant No. 10151503102000034) and Research Foundation of Shantou University Medical College (Grant No. LC0401). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 0 Z9 2 U1 2 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 24 PY 2012 VL 7 IS 5 AR e37964 DI 10.1371/journal.pone.0037964 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UB UT WOS:000305338900065 PM 22655088 ER PT J AU Moore, FE Reyon, D Sander, JD Martinez, SA Blackburn, JS Khayter, C Ramirez, CL Joung, JK Langenau, DM AF Moore, Finola E. Reyon, Deepak Sander, Jeffry D. Martinez, Sarah A. Blackburn, Jessica S. Khayter, Cyd Ramirez, Cherie L. Joung, J. Keith Langenau, David M. TI Improved Somatic Mutagenesis in Zebrafish Using Transcription Activator-Like Effector Nucleases (TALENs) SO PLOS ONE LA English DT Article ID ZINC-FINGER NUCLEASES; TARGETED GENE DISRUPTION; POOL ENGINEERING OPEN; MICROINJECTION; KNOCKOUT AB Zinc Finger Nucleases (ZFNs) made by Context-Dependent Assembly (CoDA) and Transcription Activator-Like Effector Nucleases (TALENs) provide robust and user-friendly technologies for efficiently inactivating genes in zebrafish. These designer nucleases bind to and cleave DNA at particular target sites, inducing error-prone repair that can result in insertion or deletion mutations. Here, we assess the relative efficiencies of these technologies for inducing somatic DNA mutations in mosaic zebrafish. We find that TALENs exhibited a higher success rate for obtaining active nucleases capable of inducing mutations than compared with CoDA ZFNs. For example, all six TALENs tested induced DNA mutations at genomic target sites while only a subset of CoDA ZFNs exhibited detectable rates of mutagenesis. TALENs also exhibited higher mutation rates than CoDA ZFNs that had not been pre-screened using a bacterial two-hybrid assay, with DNA mutation rates ranging from 20%-76.8% compared to 1.1%-3.3%. Furthermore, the broader targeting range of TALENs enabled us to induce mutations at the methionine translation start site, sequences that were not targetable using the CoDA ZFN platform. TALENs exhibited similar toxicity to CoDA ZFNs, with >50% of injected animals surviving to 3 days of life. Taken together, our results suggest that TALEN technology provides a robust alternative to CoDA ZFNs for inducing targeted gene-inactivation in zebrafish, making it a preferred technology for creating targeted knockout mutants in zebrafish. C1 [Moore, Finola E.; Reyon, Deepak; Sander, Jeffry D.; Martinez, Sarah A.; Blackburn, Jessica S.; Khayter, Cyd; Ramirez, Cherie L.; Joung, J. Keith; Langenau, David M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Moore, Finola E.; Reyon, Deepak; Sander, Jeffry D.; Martinez, Sarah A.; Blackburn, Jessica S.; Khayter, Cyd; Ramirez, Cherie L.; Joung, J. Keith; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Moore, Finola E.; Martinez, Sarah A.; Blackburn, Jessica S.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA USA. [Moore, Finola E.; Reyon, Deepak; Sander, Jeffry D.; Martinez, Sarah A.; Blackburn, Jessica S.; Khayter, Cyd; Ramirez, Cherie L.; Joung, J. Keith; Langenau, David M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Reyon, Deepak; Sander, Jeffry D.; Khayter, Cyd; Ramirez, Cherie L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. RP Moore, FE (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. EM dlangenau@partners.org FU Alex's Lemonade Stand Foundation; American Cancer Society; Harvard Stem Cell Institute; NIH [K01 AR055619, RO1 CA154923, R21 CA156056, DP1 OD006862, R01 GM088040, T32 CA009216]; Jim and Ann Orr MGH Research Scholar Award; National Science Foundation [DBI-0923827] FX D.M.L. is supported by NIH grants K01 AR055619, RO1 CA154923, and R21 CA156056, the Alex's Lemonade Stand Foundation, the American Cancer Society, and the Harvard Stem Cell Institute. J.K.J. is supported by an NIH Director's Pioneer Award (DP1 OD006862), NIH R01 GM088040, and the Jim and Ann Orr MGH Research Scholar Award. J.D.S. is supported by NIH T32 CA009216. D. R. is supported by National Science Foundation award DBI-0923827. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 88 Z9 96 U1 1 U2 49 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 24 PY 2012 VL 7 IS 5 AR e37877 DI 10.1371/journal.pone.0037877 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UB UT WOS:000305338900052 PM 22655075 ER PT J AU Koleva, RI Ficarro, SB Radomska, HS Carrasco-Alfonso, MJ Alberta, JA Webber, JT Luckey, CJ Marcucci, G Tenen, DG Marto, JA AF Koleva, Rositsa I. Ficarro, Scott B. Radomska, Hanna S. Carrasco-Alfonso, Marlene J. Alberta, John A. Webber, James T. Luckey, C. John Marcucci, Guido Tenen, Daniel G. Marto, Jarrod A. TI C/EBP alpha and DEK coordinately regulate myeloid differentiation SO BLOOD LA English DT Article ID BINDING PROTEIN-ALPHA; ACUTE MYELOGENOUS LEUKEMIA; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; PROTEOMIC IDENTIFICATION; NEUTROPHIL DEVELOPMENT; CD34(+) CELLS; SELF-RENEWAL; IN-VIVO; PHOSPHORYLATION AB The transcription factor C/EBP alpha is a critical mediator of myeloid differentiation and is often functionally impaired in acute myeloid leukemia. Recent studies have suggested that oncogenic FLT3 activity disrupts wild-type C/EBP alpha function via phosphorylation on serine 21 (S21). Despite the apparent role of pS21 as a negative regulator of C/EBP alpha transcription activity, the mechanism by which phosphorylation tips the balance between transcriptionally competent and inhibited forms remains unresolved. In the present study, we used immuno-affinity purification combined with quantitative mass spectrometry to delineate the proteins associated with C/EBP alpha on chromatin. We identified DEK, a protein with genetic links to leukemia, as a member of the C/EBP alpha complexes, and demonstrate that this association is disrupted by S21 phosphorylation. We confirmed that DEK is recruited specifically to chromatin with C/EBP alpha to enhance GCSFR3 promoter activation. In addition, we demonstrated that genetic depletion of DEK reduces the ability of C/EBP alpha to drive the expression of granulocytic target genes in vitro and disrupts G-CSF-mediated granulocytic differentiation of fresh human BM-derived CD34(+) cells. Our data suggest that C/EBP alpha and DEK coordinately activate myeloid gene expression and that S21 phosphorylation on wild-type C/EBP alpha mediates protein interactions that regulate the differentiation capacity of hematopoietic progenitors. (Blood. 2012;119(21): 4878-4888) C1 [Koleva, Rositsa I.; Ficarro, Scott B.; Alberta, John A.; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Koleva, Rositsa I.; Ficarro, Scott B.; Webber, James T.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Radomska, Hanna S.; Tenen, Daniel G.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Radomska, Hanna S.; Tenen, Daniel G.] Harvard Univ, Stem Cell Inst, Ctr Life Sci, Boston, MA 02115 USA. [Carrasco-Alfonso, Marlene J.; Luckey, C. John] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Marcucci, Guido] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117548, Singapore. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 1158A, Boston, MA 02215 USA. EM jarrod_marto@dfci.harvard.edu FU Dana-Farber Cancer Institute; National Institutes of Health [P01NS047572, P30 CA016058, CA118316, DK080665] FX This work was supported by the Dana-Farber Cancer Institute, and the National Institutes of Health (P01NS047572 to J.M., P30 CA016058 to G. M., and CA118316 and DK080665 to D.T.). NR 49 TC 22 Z9 22 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 24 PY 2012 VL 119 IS 21 BP 4878 EP 4888 DI 10.1182/blood-2011-10-383083 PG 11 WC Hematology SC Hematology GA 959CZ UT WOS:000305290400014 PM 22474248 ER PT J AU Arnason, JE Campigotto, F Neuberg, D Bussel, JB AF Arnason, Jon E. Campigotto, Federico Neuberg, Donna Bussel, James B. TI Abnormalities in IgA and IgM are associated with treatment-resistant ITP SO BLOOD LA English DT Article ID THROMBOCYTOPENIC PURPURA; IMMUNE THROMBOCYTOPENIA AB We hypothesized that immune dysregulation, as represented by abnormal immunoglobulin (Ig) levels, may increase immune thrombocytopenia (ITP) severity. A cross-sectional analysis was performed encompassing patients with ITP seen at the New York Presbyterian Platelet Disorder Center in the past 10 years. The subjects' Ig levels were measured, and subjects were analyzed for differences in treatment response. Subjects with an IgA level greater than median had a significantly increased chance of failing to respond to standard treatment (steroids, intravenous Ig, and intravenous anti-D) than did subjects with an IgA level lower than median (37 of 271, 14%; vs 22 of 281, 8%; P = .03) and an increased risk for bleeding (36 of 378, 10%; vs 19 of 386, 5%; P = .02). Subjects with an IgM less than 56 (lower limit of normal) failed to respond to standard treatment more often than patients with a normal IgM (12 of 67, 18%; vs 44 of 467, 9%; P = .05) with a trend toward worsened response to splenectomy (3 of 18, 17%; vs 36 of 86, 42%; P = .06). These observations suggest that immune dysregulation, as represented by elevations in IgA or decreased levels of IgM, are associated with ITP that is more resistant to treatment. (Blood. 2012;119(21):5016-5020) C1 [Arnason, Jon E.] Harvard Univ, Hematol Malignancy & Bone Marrow Transplantat Pro, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bussel, James B.] Weill Cornell Med Ctr, New York, NY USA. RP Arnason, JE (reprint author), Harvard Univ, Hematol Malignancy & Bone Marrow Transplantat Pro, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. EM jarnason@bidmc.harvard.edu FU Amgen; Cangene; GlaxoSmithKline; Genzyme; IgG of America; Immunomedics; Ligand; Eisai Inc; Shionogi; Sysmex FX J.B.B. currently receives clinical research support from the following companies: Amgen, Cangene, GlaxoSmithKline, Genzyme, IgG of America, Immunomedics, Ligand, Eisai Inc, Shionogi, and Sysmex. His family owns stock in Amgen and GlaxoSmithKline. He has participated in Advisory Boards for Amgen, GlaxoSmithKline, Ligand, Shionogi, and Eisai Inc. He also had a 1-day consult with Portola. The remaining authors declare no competing financial interests. NR 9 TC 4 Z9 5 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 24 PY 2012 VL 119 IS 21 BP 5016 EP 5020 DI 10.1182/blood-2011-09-381020 PG 5 WC Hematology SC Hematology GA 959CZ UT WOS:000305290400028 PM 22490683 ER PT J AU Lee, JS FitzGibbon, EJ Chen, YR Kim, HJ Lustig, LR Akintoye, SO Collins, MT Kaban, LB AF Lee, J. S. FitzGibbon, E. J. Chen, Y. R. Kim, H. J. Lustig, L. R. Akintoye, S. O. Collins, M. T. Kaban, L. B. TI Clinical guidelines for the management of craniofacial fibrous dysplasia SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article ID MCCUNE-ALBRIGHT-SYNDROME; OPTICAL COHERENCE TOMOGRAPHY; STIMULATORY G-PROTEIN; ANTERIOR SKULL BASE; TEMPORAL BONE; PARANASAL SINUSES; PAMIDRONATE TREATMENT; MALIGNANT TRANSFORMATION; ACTIVATING MUTATIONS; FIBROOSSEOUS LESIONS AB Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic, activating mutations of the GNAS gene that results in inhibition of the differentiation and proliferation of bone-forming stromal cells and leads to the replacement of normal bone and marrow by fibrous tissue and woven bone. The phenotype is variable and may be isolated to a single skeletal site or multiple sites and sometimes is associated with extraskeletal manifestations in the skin and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and progression of FD may also vary, thereby making the management of this condition difficult with few established clinical guidelines. This paper provides a clinically-focused comprehensive description of craniofacial FD, its natural progression, the components of the diagnostic evaluation and the multi-disciplinary management, and considerations for future research. C1 [Lee, J. S.] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. [FitzGibbon, E. J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Chen, Y. R.] Chang Gung Univ, Chang Gung Mem Hosp, Chang Gung Craniofacial Ctr, Tao Yuan, Taiwan. [Kim, H. J.] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA. [Kim, H. J.] Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. [Lustig, L. R.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA. [Akintoye, S. O.] Univ Penn, Sch Dent Med, Dept Oral Med, Philadelphia, PA 19104 USA. [Collins, M. T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Kaban, L. B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Walter C Guralnick Prof & Chairman Dept Oral & Ma, Boston, MA 02115 USA. RP Lee, JS (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. FU Fibrous Dysplasia Foundation; Zimmer FX This article has been published as part of Orphanet Journal of Rare Diseases Volume 7 Supplement 1, 2012: Proceedings of the International Meeting on McCune-Albright Syndrome and Cherubism. The full contents of the supplement are available online at http://www.ojrd.com/supplements/7/S1. Publication of the proceedings was funded by the Fibrous Dysplasia Foundation and an unrestricted grant from Zimmer. NR 100 TC 26 Z9 27 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD MAY 24 PY 2012 VL 7 SU 1 AR S2 DI 10.1186/1750-1172-7-S1-S2 PG 19 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 951YJ UT WOS:000304756300002 PM 22640797 ER PT J AU Papadaki, ME Lietman, SA Levine, MA Olsen, BR Kaban, LB Reichenberger, EJ AF Papadaki, Maria E. Lietman, Steven A. Levine, Michael A. Olsen, Bjorn R. Kaban, Leonard B. Reichenberger, Ernst J. TI Cherubism: best clinical practice SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article ID GIANT-CELL LESIONS; ADAPTER PROTEIN 3BP2; TNF-ALPHA BLOCKADE; JAW TUMOR SYNDROME; TERM-FOLLOW-UP; NOONAN-SYNDROME; GINGIVAL FIBROMATOSIS; AGGRESSIVE-BEHAVIOR; ORBITAL INVOLVEMENT; CYTOLOGIC FEATURES AB Cherubism is a skeletal dysplasia characterized by bilateral and symmetric fibro-osseous lesions limited to the mandible and maxilla. In most patients, cherubism is due to dominant mutations in the SH3BP2 gene on chromosome 4p16.3. Affected children appear normal at birth. Swelling of the jaws usually appears between 2 and 7 years of age, after which, lesions proliferate and increase in size until puberty. The lesions subsequently begin to regress, fill with bone and remodel until age 30, when they are frequently not detectable. Fibro-osseous lesions, including those in cherubism have been classified as quiescent, non-aggressive and aggressive on the basis of clinical behavior and radiographic findings. Quiescent cherubic lesions are usually seen in older patients and do not demonstrate progressive growth. Non-aggressive lesions are most frequently present in teenagers. Lesions in the aggressive form of cherubism occur in young children and are large, rapidly growing and may cause tooth displacement, root resorption, thinning and perforation of cortical bone. Because cherubism is usually self-limiting, operative treatment may not be necessary. Longitudinal observation and follow-up is the initial management in most cases. Surgical intervention with curettage, contouring or resection may be indicated for functional or aesthetic reasons. Surgical procedures are usually performed when the disease becomes quiescent. Aggressive lesions that cause severe functional problems such as airway obstruction justify early surgical intervention. C1 [Reichenberger, Ernst J.] Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, Ctr Regenerat Med & Skeletal Dev, Farmington, CT USA. [Papadaki, Maria E.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Lietman, Steven A.] Cleveland Clin, Lerner Res Inst, Dept Orthopaed Surg, Cleveland, OH 44106 USA. [Lietman, Steven A.] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44106 USA. [Levine, Michael A.] Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA. [Levine, Michael A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Olsen, Bjorn R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Reichenberger, EJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, Ctr Regenerat Med & Skeletal Dev, Farmington, CT USA. EM reichenberger@uchc.edu OI Levine, Michael/0000-0003-0036-7809 FU Fibrous Dysplasia Foundation; NIH (National Institutes of Dental and Craniofacial Research); NIH (Office of Rare Diseases); Zimmer FX Written consent for publication was obtained from patients or their relatives. This study was supported by funding from the Fibrous Dysplasia Foundation and the NIH (National Institutes of Dental and Craniofacial Research and the Office of Rare Diseases).; This article has been published as part of Orphanet Journal of Rare Diseases Volume 7 Supplement 1, 2012: International Meeting on Fibrous Dysplasia/McCune-Albright Syndrome and Cherubism. The full contents of the supplement are available online at http://www.ojrd.com/supplements/7/S1. Publication of the proceedings was funded by the Fibrous Dysplasia Foundation and an unrestricted grant from Zimmer. NR 99 TC 25 Z9 25 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD MAY 24 PY 2012 VL 7 SU 1 AR S6 DI 10.1186/1750-1172-7-S1-S6 PG 14 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 951YJ UT WOS:000304756300006 PM 22640403 ER PT J AU Reichenberger, EJ Levine, MA Olsen, BR Papadaki, ME Lietman, SA AF Reichenberger, Ernst J. Levine, Michael A. Olsen, Bjorn R. Papadaki, Maria E. Lietman, Steven A. TI The role of SH3BP2 in the pathophysiology of cherubism SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article ID ADAPTER PROTEIN 3BP2; WOLF-HIRSCHHORN-SYNDROME; CELL LESION SYNDROME; PHOSPHOLIPASE-C-GAMMA; NEUROFIBROMATOSIS-NOONAN-SYNDROME; ANTIGEN RECEPTOR; T-CELLS; REGULATES OSTEOCLASTOGENESIS; TRANSCRIPTION FACTOR; PTPN11 MUTATIONS AB Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans. C1 [Reichenberger, Ernst J.] Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, Ctr Regenerat Med & Skeletal Dev, Farmington, CT USA. [Levine, Michael A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Levine, Michael A.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA. [Olsen, Bjorn R.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Papadaki, Maria E.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Lietman, Steven A.] Cleveland Clin, Lerner Res Inst, Dept Orthopaed Surg, Cleveland, OH 44106 USA. [Lietman, Steven A.] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44106 USA. RP Reichenberger, EJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, Ctr Regenerat Med & Skeletal Dev, Farmington, CT USA. EM reichenberger@uchc.edu OI Levine, Michael/0000-0003-0036-7809 FU National Institute of Dental and Craniofacial Research; Office of Rare Diseases; NIH; Fibrous Dysplasia Foundation; Zimmer, Inc.; Zimmer FX This article was developed as part of the Proceedings of the International Meeting on Fibrous Dysplasia/McCune-Albright Syndrome and Cherubism that took place at the National Institutes of Health, Bethesda, MD, October 3-5, 2010. The meeting was supported by funding from the National Institute of Dental and Craniofacial Research and Office of Rare Diseases, NIH, and the Fibrous Dysplasia Foundation. The publication of this manuscript was supported by the Fibrous Dysplasia Foundation and an unrestricted grant from Zimmer, Inc.; This article has been published as part of Orphanet Journal of Rare Diseases Volume 7 Supplement 1, 2012: International Meeting on Fibrous Dysplasia/McCune-Albright Syndrome and Cherubism. The full contents of the supplement are available online at http://www.ojrd.com/supplements/7/S1. Publication of the proceedings was funded by the Fibrous Dysplasia Foundation and an unrestricted grant from Zimmer. NR 102 TC 26 Z9 27 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD MAY 24 PY 2012 VL 7 SU 1 AR S5 DI 10.1186/1750-1172-7-S1-S5 PG 12 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 951YJ UT WOS:000304756300005 PM 22640988 ER PT J AU Stanton, RP Ippolito, E Springfield, D Lindaman, L Wientroub, S Leet, A AF Stanton, Robert P. Ippolito, Ernesto Springfield, Dempsey Lindaman, Lynn Wientroub, Shlomo Leet, Arabella TI The surgical management of fibrous dysplasia of bone SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article ID SKELETAL LESIONS; PAMIDRONATE AB The surgical management of Polyostotic Fibrous Dysplasia (FD) of bone is technically demanding. The most effective methods to manage the associated bone deformity remain unclear. The marked variation in the degree and pattern of bone involvement has made it difficult to acquire data to guide the surgeon's approach to these patients. In light of the paucity of data, but need for guidance, recognized experts in the management of these patients came together at the National Institutes of Health in Bethesda, Maryland as part of an International meeting to address issues related to fibrous dysplasia of bone to discuss and refine their recommendations regarding the surgical indications and preferred methods for the management of these challenging patients. The specific challenges, recommended approaches, and "lessons learned" are presented in hopes that surgeons faced with typical deformities can be guided in the surgical reconstruction of both children and adults with FD. C1 [Stanton, Robert P.] Nemours Childrens Clin, Pensacola, FL USA. [Ippolito, Ernesto] Univ Roma Tor Vergata, Dept Orthoped Surg, Rome, Italy. [Springfield, Dempsey] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lindaman, Lynn] Lindaman Orthoped, Des Moines, IA USA. [Wientroub, Shlomo] Tel Aviv Univ, Dana Childrens Hosp, IL-69978 Tel Aviv, Israel. [Leet, Arabella] Johns Hopkins Univ, Baltimore, MD USA. RP Stanton, RP (reprint author), Nemours Childrens Clin, Pensacola, FL USA. FU National Institute of Dental and Craniofacial Research; Fibrous Dysplasia Foundation; Zimmer, Inc.; Zimmer; Office of Rare Diseases; NIH FX This article was developed as part of the Proceedings of the International Meeting on Fibrous Dysplasia/McCune-Albright Syndrome and Cherubism that took place at the National Institutes of Health, Bethesda, MD, October 3-5, 2010. The meeting was supported by funding from the National Institute of Dental and Craniofacial Research and Office of Rare Diseases, NIH, and the Fibrous Dysplasia Foundation. The publication of this manuscript was supported by the Fibrous Dysplasia Foundation and an unrestricted grant from Zimmer, Inc.; This article has been published as part of Orphanet Journal of Rare Diseases Volume 7 Supplement 1, 2012: International Meeting on Fibrous Dysplasia/McCune-Albright Syndrome and Cherubism. The full contents of the supplement are available online at http://www.ojrd.com/supplements/7/S1. Publication of the proceedings was funded by the Fibrous Dysplasia Foundation and an unrestricted grant from Zimmer. NR 16 TC 19 Z9 23 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD MAY 24 PY 2012 VL 7 SU 1 AR S1 DI 10.1186/1750-1172-7-S1-S1 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 951YJ UT WOS:000304756300001 PM 22640754 ER PT J AU Gimenez-Cassina, A Martinez-Francois, JR Fisher, JK Szlyk, B Polak, K Wiwczar, J Tanner, GR Lutas, A Yellen, G Danial, NN AF Gimenez-Cassina, Alfredo Martinez-Francois, Juan Ramon Fisher, Jill K. Szlyk, Benjamin Polak, Klaudia Wiwczar, Jessica Tanner, Geoffrey R. Lutas, Andrew Yellen, Gary Danial, Nika N. TI BAD-Dependent Regulation of Fuel Metabolism and K-ATP Channel Activity Confers Resistance to Epileptic Seizures SO NEURON LA English DT Article ID KETOGENIC DIET INCREASES; GLYCEMIC-INDEX TREATMENT; KAINIC ACID; DEFICIENT MICE; CELL-DEATH; SYNAPTIC-TRANSMISSION; INSULIN-SECRETION; DENTATE GYRUS; DUAL ROLE; BRAIN AB Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phosphoregulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive K-ATP channels in neurons, as well as resistance to behavioral and electrographic seizures in vivo. Seizure resistance is reversed by genetic ablation of the K-ATP channel, implicating the BAD-K-ATP axis in metabolic control of neuronal excitation and seizure responses. C1 [Martinez-Francois, Juan Ramon; Tanner, Geoffrey R.; Lutas, Andrew; Yellen, Gary] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Gimenez-Cassina, Alfredo; Danial, Nika N.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Gimenez-Cassina, Alfredo; Fisher, Jill K.; Szlyk, Benjamin; Polak, Klaudia; Wiwczar, Jessica; Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Yellen, G (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM gary_yellen@hms.harvard.edu; nika_danial@dfci.harvard.edu OI Lutas, Andrew/0000-0002-6991-2898; Gimenez-Cassina, Alfredo/0000-0002-2768-2350; Yellen, Gary/0000-0003-4228-7866 FU Ministerio de Educacion y Ciencia (MEC, Spain); Burroughs Wellcome Fund Career Award in Biomedical Sciences; U.S. National Institutes of Health [K01CA106596, R01 NS055031, R56 NS072142]; NIH [UL1 RR025758]; CURE FX We thank Marina Godes and Juan Quijada for technical assistance and animal husbandry; Gregory Holmes for advice on EEG acquisition and analysis; Rosalind Segal, Bernardo Sabatini, Qiufu Ma, S. Robert Datta, and members of the Danial and Yellen laboratories for critical reading of this manuscript and valuable discussions; and E. Smith for manuscript preparation. A.G.C. was supported by a postdoctoral fellowship from the Ministerio de Educacion y Ciencia (MEC, Spain). N.N.D. is a recipient of the Burroughs Wellcome Fund Career Award in Biomedical Sciences. This work was supported by the U.S. National Institutes of Health grants (K01CA106596 to N.N.D., R01 NS055031 to G.Y., and R56 NS072142 to N.N.D. and G.Y.), Harvard Catalyst Pilot Award (based on NIH UL1 RR025758 to N.N.D. and G.Y.), and a CURE Epilepsy Challenge Award (G.Y. and N.N.D.). NR 66 TC 52 Z9 52 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 24 PY 2012 VL 74 IS 4 BP 719 EP 730 DI 10.1016/j.neuron.2012.03.032 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 951VD UT WOS:000304747200015 PM 22632729 ER PT J AU Zeigerer, A Gilleron, J Bogorad, RL Marsico, G Nonaka, H Seifert, S Epstein-Barash, H Kuchimanchi, S Peng, CG Ruda, VM Del Conte-Zerial, P Hengstler, JG Kalaidzidis, Y Koteliansky, V Zerial, M AF Zeigerer, Anja Gilleron, Jerome Bogorad, Roman L. Marsico, Giovanni Nonaka, Hidenori Seifert, Sarah Epstein-Barash, Hila Kuchimanchi, Satya Peng, Chang Geng Ruda, Vera M. Del Conte-Zerial, Perla Hengstler, Jan G. Kalaidzidis, Yannis Koteliansky, Victor Zerial, Marino TI Rab5 is necessary for the biogenesis of the endolysosomal system in vivo SO NATURE LA English DT Article ID POLARIZED EPITHELIAL-CELLS; LIPID-LIKE MATERIALS; RECYCLING ENDOSOMES; MEMBRANE-FUSION; PLASMA-MEMBRANE; RNAI THERAPEUTICS; ENDOCYTIC PATHWAY; TRAFFICKING; PROTEINS; TRANSPORT AB An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system. C1 [Zeigerer, Anja; Gilleron, Jerome; Marsico, Giovanni; Nonaka, Hidenori; Seifert, Sarah; Del Conte-Zerial, Perla; Kalaidzidis, Yannis; Zerial, Marino] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. [Bogorad, Roman L.; Koteliansky, Victor] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Epstein-Barash, Hila; Kuchimanchi, Satya; Peng, Chang Geng; Koteliansky, Victor] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA. [Ruda, Vera M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ruda, Vera M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ruda, Vera M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hengstler, Jan G.] Leibniz Res Ctr Working Environm & Human Factors, D-44139 Dortmund, Germany. [Kalaidzidis, Yannis] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119899, Russia. RP Zerial, M (reprint author), Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. EM zerial@mpi-cbg.de RI Bogorad, Roman/G-2609-2011; Hengstler, Jan/O-1415-2013; Kalaidzidis, Yannis/H-3094-2016; OI Kalaidzidis, Yannis/0000-0002-6137-1193; Zeigerer, Anja/0000-0003-4072-0566; Gilleron, Jerome/0000-0002-6389-8685 FU Virtual Liver initiative; German Federal Ministry of Research and Education (BMBF); Max Planck Society (MPG); DFG; Marie Curie Action, Intra-European Fellowship [fp7-people-ief-2008]; EMBO FX We acknowledge K. Simons, E. Knust, C. Fetzer, T. Galvez, G. O'Sullivan and M. P. McShane for discussions and comments on the manuscript. We thank W. John and A. Muench-Wuttke from the Biomedical Services Facility for mouse care and injections. We acknowledge J. Peychl for the management of the Light Microscopy Facility and K. Manygoats as well as J.-M. Verbavatz for their support. We thank B. Bettencourt and J. Hettinger for siRNA design and serum biochemistry assays, respectively. This work was financially supported by the Virtual Liver initiative (http://www.virtual-liver.de), funded by the German Federal Ministry of Research and Education (BMBF), the Max Planck Society (MPG) and the DFG. A.Z. was supported by a grant from Marie Curie Action, Intra-European Fellowship (fp7-people-ief-2008) and J. G. from an EMBO long-term fellowship. NR 49 TC 119 Z9 122 U1 1 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 24 PY 2012 VL 485 IS 7399 BP 465 EP 470 DI 10.1038/nature11133 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946IH UT WOS:000304344500035 PM 22622570 ER PT J AU Berger, MF Hodis, E Heffernan, TP Deribe, YL Lawrence, MS Protopopov, A Ivanova, E Watson, IR Nickerson, E Ghosh, P Zhang, HL Zeid, R Ren, XJ Cibulskis, K Sivachenko, AY Wagle, N Sucker, A Sougnez, C Onofrio, R Ambrogio, L Auclair, D Fennell, T Carter, SL Drier, Y Stojanov, P Singer, MA Voet, D Jing, R Saksena, G Barretina, J Ramos, AH Pugh, TJ Stransky, N Parkin, M Winckler, W Mahan, S Ardlie, K Baldwin, J Wargo, J Schadendorf, D Meyerson, M Gabriel, SB Golub, TR Wagner, SN Lander, ES Getz, G Chin, L Garraway, LA AF Berger, Michael F. Hodis, Eran Heffernan, Timothy P. Deribe, Yonathan Lissanu Lawrence, Michael S. Protopopov, Alexei Ivanova, Elena Watson, Ian R. Nickerson, Elizabeth Ghosh, Papia Zhang, Hailei Zeid, Rhamy Ren, Xiaojia Cibulskis, Kristian Sivachenko, Andrey Y. Wagle, Nikhil Sucker, Antje Sougnez, Carrie Onofrio, Robert Ambrogio, Lauren Auclair, Daniel Fennell, Timothy Carter, Scott L. Drier, Yotam Stojanov, Petar Singer, Meredith A. Voet, Douglas Jing, Rui Saksena, Gordon Barretina, Jordi Ramos, Alex H. Pugh, Trevor J. Stransky, Nicolas Parkin, Melissa Winckler, Wendy Mahan, Scott Ardlie, Kristin Baldwin, Jennifer Wargo, Jennifer Schadendorf, Dirk Meyerson, Matthew Gabriel, Stacey B. Golub, Todd R. Wagner, Stephan N. Lander, Eric S. Getz, Gad Chin, Lynda Garraway, Levi A. TI Melanoma genome sequencing reveals frequent PREX2 mutations SO NATURE LA English DT Article ID HUMAN CANCER; MALIGNANT-MELANOMA; SOMATIC MUTATIONS; INHIBITION; PATTERNS; BRAF; REARRANGEMENTS; SPECIFICITY; ACTIVATION; SURVIVAL AB Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life(1). To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)-a PTEN-interacting protein and negative regulator of PTEN in breast cancer(2)-as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. C1 [Berger, Michael F.; Hodis, Eran; Lawrence, Michael S.; Nickerson, Elizabeth; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sougnez, Carrie; Onofrio, Robert; Ambrogio, Lauren; Auclair, Daniel; Fennell, Timothy; Carter, Scott L.; Stojanov, Petar; Voet, Douglas; Jing, Rui; Saksena, Gordon; Barretina, Jordi; Ramos, Alex H.; Pugh, Trevor J.; Stransky, Nicolas; Parkin, Melissa; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Meyerson, Matthew; Gabriel, Stacey B.; Golub, Todd R.; Lander, Eric S.; Getz, Gad; Chin, Lynda; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Heffernan, Timothy P.; Deribe, Yonathan Lissanu; Protopopov, Alexei; Ivanova, Elena; Watson, Ian R.; Ghosh, Papia; Zhang, Hailei; Zeid, Rhamy; Ren, Xiaojia; Wagle, Nikhil; Singer, Meredith A.; Pugh, Trevor J.; Meyerson, Matthew; Chin, Lynda; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wagle, Nikhil; Ramos, Alex H.; Pugh, Trevor J.; Meyerson, Matthew; Chin, Lynda; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sucker, Antje; Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, D-45122 Essen, Germany. [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. [Wargo, Jennifer] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Meyerson, Matthew; Golub, Todd R.; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Wagner, Stephan N.] Med Univ Vienna, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1090 Vienna, Austria. [Wagner, Stephan N.] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria. [Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Chin, L (reprint author), Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Dept Genom Med, Houston, TX 77030 USA. EM LChin@mdanderson.org; levi_garraway@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Drier, Yotam/K-5208-2012; OI Drier, Yotam/0000-0003-1725-2995; Wagner, Stephan/0000-0003-4941-7029 FU National Human Genome Research Institute; National Cancer Institute; FWF-Austrian Science Fund; NIH; Melanoma Research Alliance; Starr Cancer Consortium; Burroughs-Wellcome Fund FX Illumina sequencing was performed at the Broad Institute and array-based genomic characterization and functional studies were performed at the Belfer Institute of DFCI. We are grateful to the Broad Institute Genome Sequencing Platform, Genome Analysis Platform and Biological Samples Platform. This work was supported by the National Human Genome Research Institute (S. B. G., E. S. L.), National Cancer Institute (M. M., L. C.), FWF-Austrian Science Fund (S.N.W.), NIH Director's New Innovator Award (L. A. G.), Melanoma Research Alliance (L. A. G., L. C.), Starr Cancer Consortium (L.A.G.) and the Burroughs-Wellcome Fund (L.A.G.). NR 29 TC 323 Z9 331 U1 5 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 24 PY 2012 VL 485 IS 7399 BP 502 EP 506 DI 10.1038/nature11071 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946IH UT WOS:000304344500043 PM 22622578 ER PT J AU Baselga, J Smith, BL Rafferty, EA Bombonati, A AF Baselga, Jose Smith, Barbara Lynn Rafferty, Elizabeth A. Bombonati, Alessandro TI Case 16-2012: A 32-Year-Old Woman with HER2-Positive Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HER2/NEU-OVEREXPRESSING METASTATIC BREAST; NERVOUS-SYSTEM METASTASES; MONOCLONAL-ANTIBODY; PHASE-II; PRIMARY TUMOR; 1ST-LINE TREATMENT; BRAIN METASTASES; TRASTUZUMAB; SURVIVAL; CHEMOTHERAPY C1 [Baselga, Jose] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Smith, Barbara Lynn] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bombonati, Alessandro] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Baselga, Jose] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Smith, Barbara Lynn] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rafferty, Elizabeth A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Bombonati, Alessandro] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 31 TC 6 Z9 6 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 24 PY 2012 VL 366 IS 21 BP 2018 EP 2026 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 946LL UT WOS:000304353000013 PM 22621630 ER PT J AU Patel, SR Sheth, SA Mian, MK Gale, JT Greenberg, BD Dougherty, DD Eskandar, EN AF Patel, Shaun R. Sheth, Sameer A. Mian, Matthew K. Gale, John T. Greenberg, Benjamin D. Dougherty, Darin D. Eskandar, Emad N. TI Single-Neuron Responses in the Human Nucleus Accumbens during a Financial Decision-Making Task SO JOURNAL OF NEUROSCIENCE LA English DT Article ID BEHAVIORAL-CONTROL; REWARD-SEEKING; DOPAMINE; PREDICTION; STRIATUM; ERRORS; ROLES; BRAIN AB Linking values to actions and evaluating expectations relative to outcomes are both central to reinforcement learningandarethoughtto underlie financial decision-making. However, neurophysiology studies of these processes in humans remain limited. Here, we recorded the activity of single human nucleus accumbens neurons while subjects performed a gambling task. We show that the nucleus accumbens encodes two signals related to subject behavior. First, we find that under relatively predictable conditions, single neuronal activity predicts future financial decisions on a trial-by-trial basis. Interestingly, we show that this activity continues to predict decisions even under conditions of uncertainty (e. g., when the probability of winning or losing is 50/50 and no particular financial choice predicts a rewarding outcome). Furthermore, we find that this activity occurs, on average, 2 s before the subjects physically manifest their decision. Second, we find that the nucleus accumbens encodes the difference between expectedandrealized outcomes, consistent with a prediction error signal. We show this activity occurs immediately after the subject has realized the outcome of the trial and is present on both the individual and population neuron levels. These results provide human single neuronal evidence that the nucleus accumbens is integral in making financial decisions. C1 [Patel, Shaun R.; Sheth, Sameer A.; Mian, Matthew K.; Gale, John T.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Sch Med,Dept Neurosurg, Boston, MA 02114 USA. [Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Patel, Shaun R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Greenberg, Benjamin D.] Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Greenberg, Benjamin D.] Brown Med Sch, Providence, RI 02906 USA. RP Eskandar, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Sch Med,Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM eeskandar@partners.org FU National Science Foundation [IOB 0645886]; National Institutes of Health [NEI 1R01EY017658-01A1, NIDA 1R01NS063249]; NIMH [MH086400, R25NS065743]; Klingenstein Foundation; Howard Hughes Medical Institute FX This work was supported by grants from the National Science Foundation (IOB 0645886), the National Institutes of Health (NEI 1R01EY017658-01A1, NIDA 1R01NS063249, NIMH Conte Award MH086400, R25NS065743), the Klingenstein Foundation, and the Howard Hughes Medical Institute. We thank W.F. Asaad and L.J. Toth for their helpful comments and discussion. NR 24 TC 17 Z9 18 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 23 PY 2012 VL 32 IS 21 BP 7311 EP 7315 DI 10.1523/JNEUROSCI.0027-12.2012 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 947HR UT WOS:000304421000023 PM 22623676 ER PT J AU Ahmed, OJ Mehta, MR AF Ahmed, Omar J. Mehta, Mayank R. TI Running Speed Alters the Frequency of Hippocampal Gamma Oscillations SO JOURNAL OF NEUROSCIENCE LA English DT Article ID FREELY-MOVING RATS; HEAD-DIRECTION; PATH-INTEGRATION; PLACE CELLS; BAND SYNCHRONIZATION; ENTORHINAL CORTEX; PYRAMIDAL CELLS; VISUAL-CORTEX; UNIT-ACTIVITY; BEHAVING RAT AB Successful spatial navigation is thought to employ a combination of at least two strategies: the following of landmark cues and path integration. Path integration requires that the brain use the speed and direction of movement in a meaningful way to continuously compute the position of the animal. Indeed, the running speed of rats modulates both the firing rate of neurons and the spectral properties of low frequency, theta oscillations seen in the local field potential (LFP) of the hippocampus, a region important for spatial memory formation. Higher frequency, gamma-band LFP oscillations are usually associated with decision-making, increased attention, and improved reaction times. Here, we show that increased running speed is accompanied by large, systematic increases in the frequency of hippocampal CA1 network oscillations spanning the entire gamma range (30-120 Hz) and beyond. These speed-dependent changes in frequency are seen on both linear tracks and two-dimensional platforms, and are thus independent of the behavioral task. Synchrony between anatomically distant CA1 regions also shifts to higher gamma frequencies as running speed increases. The changes in frequency are strongly correlated with changes in the firing rates of individual interneurons, consistent with models of gamma generation. Our results suggest that as a rat runs faster, there are faster gamma frequency transitions between sequential place cell-assemblies. This may help to preserve the spatial specificity of place cells and spatial memories at vastly different running speeds. C1 [Ahmed, Omar J.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Mehta, Mayank R.] Univ Calif Los Angeles, Integrat Ctr Learning & Memory, Keck Ctr Neurophys, Dept Phys & Astron,Dept Neurol,Dept Neurobiol, Los Angeles, CA 90095 USA. RP Ahmed, OJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Thier 423, Boston, MA 02114 USA. EM omar.j.ahmed@gmail.com FU NIMH [MH081477]; W.M. Keck foundation; Whitehall foundation; NSF [0969034]; NIH/CRCNS [1-R01-MH-092925-01]; NARSAD FX This work was supported by an NIMH Predoctoral Grant (MH081477) awarded to O.J.A. and grants from the W.M. Keck foundation, the Whitehall foundation, a NARSAD Young Investigator Award, NSF Career Award #0969034, and NIH/CRCNS #1-R01-MH-092925-01 to M.R.M. We wish to thank Dr. James Knierim for his helpful comments on a previous version of this manuscript, and also Lucas Santos, James McFarland, Ammar Shaikhouni, Luk Chong Yeung, Arvind Kumar, Annie van Beuningen, Alison Boyd, Ethan Brown, Vivek Buch, Vivek Chellappa, Joshua Lai, Lyle Muller, Samuel Reiter, Hank Schilling, and Valerie Yanofsky. NR 68 TC 33 Z9 33 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 23 PY 2012 VL 32 IS 21 BP 7373 EP 7383 DI 10.1523/JNEUROSCI.5110-11.2012 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 947HR UT WOS:000304421000030 PM 22623683 ER PT J AU Loewenstein, G Asch, DA Friedman, JY Melichar, LA Volpp, KG AF Loewenstein, George Asch, David A. Friedman, Joelle Y. Melichar, Lori A. Volpp, Kevin G. TI Can behavioural economics make us healthier? SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID FINANCIAL INCENTIVES; ASYMMETRIC PATERNALISM; MEDICATION ADHERENCE; RANDOMIZED-TRIAL; COPAYMENTS; VETERANS; INCREASE; SMOKING; IMPACT AB Behavioural economics is becoming increasingly popular as a way to improve public health. George Loewenstein and colleagues point out some of the pitfalls and warn that it cannot be used as a substitute for conventional policies to tackle fundamental problems C1 [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Loewenstein, George; Asch, David A.; Friedman, Joelle Y.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Melichar, Lori A.] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. RP Loewenstein, G (reprint author), Carnegie Mellon Univ, Dept Social & Decis Sci, 208 Porter Hall,5000 Forbes Ave, Pittsburgh, PA 15213 USA. EM GL20@andrew.cmu.edu OI Asch, David/0000-0002-7970-286X NR 31 TC 17 Z9 17 U1 2 U2 27 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BRIT MED J JI Br. Med. J. PD MAY 23 PY 2012 VL 344 AR e3482 DI 10.1136/bmj.e3482 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 949QT UT WOS:000304591500011 PM 22623635 ER PT J AU Volpp, KG Loewenstein, G Asch, DA AF Volpp, Kevin G. Loewenstein, George Asch, David A. TI Assessing Value in Health Care Programs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DISEASE C1 [Volpp, Kevin G.; Asch, David A.] Univ Penn Sch, Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Loewenstein, George; Asch, David A.] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Loewenstein, George; Asch, David A.] Univ Penn, Leonard Davis Inst Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Dept Hlth Care Management, Wharton Sch Decis Sci, Philadelphia, PA 19104 USA. [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. RP Volpp, KG (reprint author), Univ Penn Sch, Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIA NIH HHS [P30 AG034546] NR 9 TC 7 Z9 7 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 23 PY 2012 VL 307 IS 20 BP 2153 EP 2154 DI 10.1001/jama.2012.3619 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 945YX UT WOS:000304315200021 PM 22618919 ER PT J AU Hung, WW Egol, KA Zuckerman, JD Siu, AL AF Hung, William W. Egol, Kenneth A. Zuckerman, Joseph D. Siu, Albert L. TI Hip Fracture Management Tailoring Care for the Older Patient SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; QUALITY-OF-LIFE; FEMORAL-NECK; ELDERLY-PATIENTS; RISK-FACTORS; BIPOLAR HEMIARTHROPLASTY; FUNCTIONAL RECOVERY; HOSPITAL DISCHARGE; HOME EXERCISE; VITAMIN-D AB Hip fracture is a potentially devastating condition for older adults. Hip fracture leads to pain and immobilization with complications ranging from delirium to functional loss and death. Although a mainstay of treatment is orthopedic repair, a multidisciplinary comanagement approach, including medical specialists and rehabilitation, may maximize patient recovery. Using the case of Mr W, an older man who sustained a fall and hip fracture, we present evidence-based components of care both in the hospital and outpatient settings. Preoperatively, clinicians should correct medical abnormalities and consider the appropriateness, timing, and type of surgical repair in the context of the patient's life expectancy and goals of care. Perioperative care should include prophylaxis with antibiotics, chemoprophylaxis for venous thromboembolism, and correction of major clinical abnormalities prior to surgery. Pain control, delirium, and pressure ulcer prevention are important inpatient care elements. Multidisciplinary models incorporating these care elements can decrease complications during inpatient stay. Rehabilitation strategies should be tailored to patient needs; early mobilization followed by rehabilitation exercises in institutional, home, and group settings should be considered to maximize restoration of locomotive abilities. Attention to care transitions is necessary and treatment for osteoporosis should be considered. The road to recovery for hip fracture patients is long and most patients may not regain their prefracture functional status. Understanding and anticipating issues that may arise in the older patient with hip fracture, while delivering evidence-based care components, is necessary to maximize patient recovery. C1 [Hung, William W.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Dev Res Enhancement Award Program, Bronx, NY USA. [Hung, William W.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Hlth Serv Res, Bronx, NY USA. [Egol, Kenneth A.; Zuckerman, Joseph D.] NYU, Hosp Joint Dis, Dept Orthopaed Surg, New York, NY USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM william.hung@mssm.edu FU Exactech; Orthopaedic Research & Education Foundation; Orthopaedic Trauma Association; New York Academy of Medicine; Claude D. Pepper Older Americans Independence Center at Mount Sinai School of Medicine [P30-AG028741]; SCAN Foundation FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Egol reports receipt of consultancy fees and royalties from Exactech; grants or pending grants from the Orthopaedic Research & Education Foundation and the Orthopaedic Trauma Association; and holding stock/stock options with Johnson & Johnson. The other authors report no disclosures.; Dr Hung is currently supported by the New York Academy of Medicine Hoar Fellowship. This article was supported in part by the Claude D. Pepper Older Americans Independence Center at Mount Sinai School of Medicine (P30-AG028741). The Care of the Aging Patient series is made possible by funding from The SCAN Foundation. NR 86 TC 53 Z9 58 U1 4 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 23 PY 2012 VL 307 IS 20 BP 2185 EP 2194 DI 10.1001/jama.2012.4842 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 945YX UT WOS:000304315200028 PM 22618926 ER PT J AU Henrickson, SE Altshuler, D AF Henrickson, Sarah E. Altshuler, David TI Risk and Return for the Clinician-Investigator SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article AB In this case study, an early-career clinician-investigator discusses impending and future career issues in an interview with an established translational scientist, who then shares ideas about pursuing clinically informed research questions. C1 [Henrickson, Sarah E.] Childrens Hosp, Boston Combined Residency Program Pediat, Boston, MA 02115 USA. [Henrickson, Sarah E.] Boston Med Ctr, Boston, MA 02115 USA. [Henrickson, Sarah E.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Altshuler, David] Cambridge Ctr, Program Med & Populat Genet, Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Altshuler, David] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02116 USA. [Altshuler, David] Harvard Univ, Dept Med, Sch Med, Boston, MA 02116 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Henrickson, SE (reprint author), Childrens Hosp, Boston Combined Residency Program Pediat, 300 Longwood Ave, Boston, MA 02115 USA. EM sarah.henrickson@childrens.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 23 PY 2012 VL 4 IS 135 AR 135cm6 DI 10.1126/scitranslmed.3004110 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 946PS UT WOS:000304365700007 PM 22623733 ER PT J AU Vogelstein, B Roberts, NJ Vogelstein, JT Parmigiani, G Kinzler, KW Velculescu, VE AF Vogelstein, Bert Roberts, Nicholas J. Vogelstein, Joshua T. Parmigiani, Giovanni Kinzler, Kenneth W. Velculescu, Victor E. TI Response to Comments on "The Predictive Capacity of Personal Genome Sequencing" SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Letter AB The power of personal genome sequencing to elucidate disease pathogenesis will ensure that it will become an essential tool in medical practice, but recognizing its limitations for improving public health will minimize false expectations and foster the most fruitful investigations. C1 [Vogelstein, Bert; Roberts, Nicholas J.; Kinzler, Kenneth W.; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. [Vogelstein, Bert; Roberts, Nicholas J.; Kinzler, Kenneth W.; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA. [Vogelstein, Joshua T.] Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD 21287 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Vogelstein, B (reprint author), Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. EM vogelbe@jhmi.edu NR 8 TC 1 Z9 1 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 23 PY 2012 VL 4 IS 135 AR 135lr3 DI 10.1126/scitranslmed.3004246 PG 2 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 946PS UT WOS:000304365700006 ER PT J AU MacArthur, DG AF MacArthur, Daniel G. TI Challenges in clinical genomics SO GENOME MEDICINE LA English DT Editorial Material AB A report on the Genomic Disorders 2012: Genomics of Rare Diseases meeting, Hinxton, UK, 21-23 March 2012. C1 [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP MacArthur, DG (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM macarthur@atgu.mgh.harvard.edu NR 0 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD MAY 22 PY 2012 VL 4 AR 43 DI 10.1186/gm342 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 084WO UT WOS:000314571000001 PM 22621759 ER PT J AU Zhang, C Montgomery, TA Fischer, SEJ Garcia, SMDA Riedel, CG Fahlgren, N Sullivan, CM Carrington, JC Ruvkun, G AF Zhang, Chi Montgomery, Taiowa A. Fischer, Sylvia E. J. Garcia, Susana M. D. A. Riedel, Christian G. Fahlgren, Noah Sullivan, Christopher M. Carrington, James C. Ruvkun, Gary TI The Caenorhabditis elegans RDE-10/RDE-11 Complex Regulates RNAi by Promoting Secondary siRNA Amplification SO CURRENT BIOLOGY LA English DT Article ID GERM-LINE DEVELOPMENT; C-ELEGANS; INTERFERENCE; GENES; DCR-1; PATHWAYS; HELICASE; HOMOLOG; REVEALS; RDE-1 AB Background: In nematodes, plants, and fungi, RNAi is remarkably potent and persistent due to the amplification of initial silencing signals by RNA-dependent RNA polymerases (RdRPs). In Caenorhabditis elegans (C. elegans), the interaction between the RNA-induced silencing complex (RISC) loaded with primary small interfering RNAs (siRNAs) and the target messenger RNA (mRNA) leads to the recruitment of RdRPs and synthesis of secondary siRNAs using the target mRNA as the template. The mechanism and genetic requirements for secondary siRNA accumulation are not well understood. Results: From a forward genetic screen for C. elegans genes required for RNAi, we identified rde-10, and through proteomic analysis of RDE-10-interacting proteins, we identified a protein complex containing the new RNAi factor RDE-11, the known RNAi factors RSD-2 and ERGO-1, and other candidate RNAi factors. The RNAi defective genes rde-10 and rde-11 encode a novel protein and a RING-type zinc finger domain protein, respectively. Mutations in rde-10 and rde-11 genes cause dosage-sensitive RNAi deficiencies: these mutants are resistant to low dosage but sensitive to high dosage of double-stranded RNAs. We assessed the roles of rde-10, rde-11, and other dosage-sensitive RNAi-defective genes rsd-2, rsd-6, and haf-6 in both exogenous and endogenous small RNA pathways using high-throughput sequencing and qRT-PCR. These genes are required for the accumulation of secondary siRNAs in both exogenous and endogenous RNAi pathways. Conclusions: The RDE-10/RDE-11 complex is essential for the amplification of RNAi in C. elegans by promoting secondary siRNA accumulation. C1 [Zhang, Chi; Montgomery, Taiowa A.; Fischer, Sylvia E. J.; Garcia, Susana M. D. A.; Riedel, Christian G.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Zhang, Chi; Montgomery, Taiowa A.; Fischer, Sylvia E. J.; Garcia, Susana M. D. A.; Riedel, Christian G.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Fahlgren, Noah; Carrington, James C.] Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA. [Sullivan, Christopher M.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruykun@molbio.mgh.harvard.edu RI Carrington, James/A-4656-2012; Fahlgren, Noah/D-4404-2011; OI Carrington, James/0000-0003-3572-129X; Fahlgren, Noah/0000-0002-5597-4537; Riedel, Christian/0000-0002-3689-8022; Montgomery, Taiowa/0000-0001-7857-3253 FU National Institutes of Health (NIH) [GM44619, AI43288]; National Science Foundation [MCB-1231726]; MGH ECOR; Damon Runyon Cancer Research Foundation [DRG-2029-09]; American Heart Association [0825938D]; European Molecular Biology Organization; Human Frontier Science Program FX We are very grateful to Huan Yang and Ho Yi Mak for rde-10 and rde-11 mutant and transgenic strains, as well as communicating unpublished data. We thank Darryl Conte, Weifeng Gu, Pedro Batista, and Daniel Chaves for providing protocols for immunoprecipitation and generation of small RNA cDNA libraries for deep sequencing; Xiaoyun Wu for protocols for large-scale immunoprecipitation; John Asara for mass spectrometry analysis; Christian Daly, Jiangwen Zhang, Mark Borowsky, Tammy Gillis, and Kaleena Shirley for Illumina deep sequencing and computational assistance; and the Caenorhabditis Genetics Center and Shohei Mitani for strains. This work was supported by a grant to G.R. from National Institutes of Health (NIH) (GM44619), grants to J.C.C. from the National Science Foundation (MCB-1231726) and NIH (AI43288), fellowships to C.Z. and S.E.J.F. from the MGH ECOR Fund for Medical Discovery, fellowship to T.A.M. from the Damon Runyon Cancer Research Foundation (DRG-2029-09), fellowship to S.M.D.A.G. from the American Heart Association (0825938D), and fellowships to C.G.R. from the European Molecular Biology Organization and the Human Frontier Science Program. NR 37 TC 18 Z9 28 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 22 PY 2012 VL 22 IS 10 BP 881 EP 890 DI 10.1016/j.cub.2012.04.011 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 947LY UT WOS:000304432700021 PM 22542102 ER PT J AU Tseng, ZH Secemsky, EA Dowdy, D Vittinghoff, E Moyers, B Wong, JK Havlir, DV Hsue, PY AF Tseng, Zian H. Secemsky, Eric A. Dowdy, David Vittinghoff, Eric Moyers, Brian Wong, Joseph K. Havlir, Diane V. Hsue, Priscilla Y. TI Sudden Cardiac Death in Patients With Human Immunodeficiency Virus Infection SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE AIDS; arrhythmia; death; sudden ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; ANTIRETROVIRAL THERAPY; HIV; MORTALITY; POPULATION; COMMUNITY; DISEASE; COHORT AB Objectives The aim of this study was to determine the incidence and clinical characteristics of sudden cardiac death (SCD) in patients with human immunodeficiency virus (HIV) infection. Background As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described. Methods The records of 2,860 consecutive patients in a public HIV clinic in San Francisco between April 2000 and August 2009 were examined. Identification of deaths, causes of death, and clinical characteristics were obtained by search of the National Death Index and/or clinic records. SCDs were determined using published retrospective criteria: 1) the International Classification of Diseases-10th Revision, code for all cardiac causes of death; and (2) circumstances of death meeting World Health Organization criteria. Results Of 230 deaths over a median of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural) diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per 1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs. 44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005), cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004), and arrhythmias (20% vs. 3%, p = 0.003). Conclusions SCDs account for most cardiac and many non-AIDS natural deaths in HIV-infected patients. Further investigation is needed to ascertain underlying mechanisms, which may include inflammation, antiretroviral therapy interruption, and concomitant medications. (J Am Coll Cardiol 2012;59:1891-6) (C) 2012 by the American College of Cardiology Foundation C1 [Tseng, Zian H.; Moyers, Brian] Univ Calif San Francisco, Cardiac Electrophysiol Sect, Div Cardiol, San Francisco, CA 94143 USA. [Secemsky, Eric A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dowdy, David] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Havlir, Diane V.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94143 USA. RP Tseng, ZH (reprint author), Univ Calif San Francisco, Cardiac Electrophysiol Sect, Div Cardiol, 500 Parnassus Ave,MU-433,Box 1354, San Francisco, CA 94143 USA. EM zhtseng@medicine.ucsf.edu FU National Heart, Lung, and Blood Institute [5R01 HL102090, 5R01 HL095130, 5R01 HL091526]; Veterans Affairs Merit Review grant [R01 NS501132]; National Institutes of Health [K24 AI51982] FX This work was supported by grants 5R01 HL102090 (Dr. Tseng), 5R01 HL095130 (Dr. Hsue), and 5R01 HL091526 (Dr. Hsue) from the National Heart, Lung, and Blood Institute; Veterans Affairs Merit Review grant R01 NS501132 (Dr. Wong); and grant K24 AI51982 (Dr. Havlir) from the National Institutes of Health. Dr. Tseng has also received minor honorarium from Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 27 TC 70 Z9 71 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 22 PY 2012 VL 59 IS 21 BP 1891 EP 1896 DI 10.1016/j.jacc.2012.02.024 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 942PF UT WOS:000304057200008 PM 22595409 ER PT J AU Wein, MN Jones, DC Shim, JH Aliprantis, AO Sulyanto, R Lazarevic, V Poliachik, SL Gross, TS Glimcher, LH AF Wein, Marc N. Jones, Dallas C. Shim, Jae-Hyuck Aliprantis, Antonios O. Sulyanto, Rosalyn Lazarevic, Vanja Poliachik, Sandra L. Gross, Ted S. Glimcher, Laurie H. TI Control of bone resorption in mice by Schnurri-3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cAMP response element binding protein; receptor activator of nuclear factor-kappa B ligand; secondary hyperparathyroidism ID DISTANT TRANSCRIPTIONAL ENHANCER; LIGAND GENE-EXPRESSION; RECEPTOR ACTIVATOR; 1,25-DIHYDROXYVITAMIN D-3; OSTEOCLAST FORMATION; TARGETED DELETION; RANKL; CELLS; MASS; OSTEOPOROSIS AB Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-kappa B ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption. C1 [Wein, Marc N.; Jones, Dallas C.; Shim, Jae-Hyuck; Aliprantis, Antonios O.; Sulyanto, Rosalyn; Lazarevic, Vanja; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Poliachik, Sandra L.; Gross, Ted S.] Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98104 USA. [Wein, Marc N.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Aliprantis, Antonios O.; Glimcher, Laurie H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA. [Glimcher, Laurie H.] Harvard Univ, Charlestown, MA 02129 USA. RP Glimcher, LH (reprint author), Weill Cornell Med Coll, Deans Off, New York, NY 10021 USA. EM lglimche@med.cornell.edu RI Lazarevic, Vanja/B-1160-2009 FU National Institutes of Health [HD055601, K99AR055668]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K08AR054859, R01AR060363] FX We thank Dorothy Zhang for histological preparations, Nicholas Brady and Mary Bouxsein for mu CT analyses, David Burr for histomorphometric analysis, Merck pharmaceuticals for assistance in generating the Shn3f/f mice, and Charles O'Brien for the RANKL reporter reagents. This work was supported by National Institutes of Health Grants HD055601 (to L.H.G.) and K99AR055668 (to D.C.J.). A.O.A. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and was supported by Grants K08AR054859 and R01AR060363 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 38 TC 8 Z9 8 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2012 VL 109 IS 21 BP 8173 EP 8178 DI 10.1073/pnas.1205848109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 947QY UT WOS:000304445800054 PM 22573816 ER PT J AU Meng, M Cherian, T Singal, G Sinha, P AF Meng, Ming Cherian, Tharian Singal, Gaurav Sinha, Pawan TI Lateralization of face processing in the human brain SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE face perception; pattern recognition; fusiform; lateralization; functional magnetic resonance imaging ID HUMAN FUSIFORM GYRUS; HUMAN VISUAL-CORTEX; OBJECT; RECOGNITION; ASYMMETRIES; HEMISPHERE; PERCEPTION; SYSTEM; AREA; PART AB Are visual face processing mechanisms the same in the left and right cerebral hemispheres? The possibility of such 'duplicated processing' seems puzzling in terms of neural resource usage, and we currently lack a precise characterization of the lateral differences in face processing. To address this need, we have undertaken a three-pronged approach. Using functional magnetic resonance imaging, we assessed cortical sensitivity to facial semblance, the modulatory effects of context and temporal response dynamics. Results on all three fronts revealed systematic hemispheric differences. We found that: (i) activation patterns in the left fusiform gyrus correlate with image-level face-semblance, while those in the right correlate with categorical face/non-face judgements. (ii) Context exerts significant excitatory/inhibitory influence in the left, but has limited effect on the right. (iii) Face-selectivity persists in the right even after activity on the left has returned to baseline. These results provide important clues regarding the functional architecture of face processing, suggesting that the left hemisphere is involved in processing 'low-level' face semblance, and perhaps is a precursor to categorical 'deep' analyses on the right. C1 [Meng, Ming] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. [Cherian, Tharian] Univ Chicago, Pritzker Sch Med, Div Biol Sci, Sch Med, Chicago, IL 60637 USA. [Singal, Gaurav] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sinha, Pawan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Meng, M (reprint author), Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. EM ming.meng@dartmouth.edu FU John Merck Foundation; Simons Foundation; James McDonnell Foundation; NEI (NIH) [R21-EY015521] FX The study was approved by the MIT Committee on the Use of Humans as Experimental Subjects (COUHES). The authors wish to thank Profs Richard Held, Sheng He, Nancy Kanwisher, Jim DiCarlo and Tomaso Poggio for their helpful feedback regarding this work. Support for this work was provided by the John Merck Foundation, the Simons Foundation, the James McDonnell Foundation and a grant from the NEI (NIH, grant number R21-EY015521). NR 34 TC 47 Z9 49 U1 2 U2 20 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD MAY 22 PY 2012 VL 279 IS 1735 BP 2052 EP 2061 DI 10.1098/rspb.2011.1784 PG 10 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 925RT UT WOS:000302779600023 PM 22217726 ER PT J AU Musunuru, K Romaine, SPR Lettre, G Wilson, JG Volcik, KA Tsai, MY Taylor, HA Schreiner, PJ Rotter, JI Rich, SS Redline, S Psaty, BM Papanicolaou, GJ Ordovas, JM Liu, K Krauss, RM Glazer, NL Gabriel, SB Fornage, M Cupples, LA Buxbaum, SG Boerwinkle, E Ballantyne, CM Kathiresan, S Rader, DJ AF Musunuru, Kiran Romaine, Simon P. R. Lettre, Guillaume Wilson, James G. Volcik, Kelly A. Tsai, Michael Y. Taylor, Herman A., Jr. Schreiner, Pamela J. Rotter, Jerome I. Rich, Stephen S. Redline, Susan Psaty, Bruce M. Papanicolaou, George J. Ordovas, Jose M. Liu, Kiang Krauss, Ronald M. Glazer, Nicole L. Gabriel, Stacey B. Fornage, Myriam Cupples, L. Adrienne Buxbaum, Sarah G. Boerwinkle, Eric Ballantyne, Christie M. Kathiresan, Sekar Rader, Daniel J. TI Multi-Ethnic Analysis of Lipid-Associated Loci: The NHLBI CARe Project SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; TRIGLYCERIDES; DESIGN; GENES; RISK AB Background: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings: We tested a set of similar to 50,000 polymorphisms from similar to 2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans. C1 [Musunuru, Kiran; Gabriel, Stacey B.] Broad Inst, Cambridge, MA USA. [Musunuru, Kiran; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Romaine, Simon P. R.] Univ Leeds, Leeds, W Yorkshire, England. [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Wilson, James G.; Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Volcik, Kelly A.; Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Taylor, Herman A., Jr.; Buxbaum, Sarah G.] Jackson State Univ, Jackson, MS USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Rich, Stephen S.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Redline, Susan] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Redline, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Papanicolaou, George J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, JM United States Dept Agr, Boston, MA 02111 USA. [Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Glazer, Nicole L.; Cupples, L. Adrienne] Boston Univ, Boston, MA 02215 USA. [Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Rader, Daniel J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Musunuru, K (reprint author), Broad Inst, Cambridge, MA USA. EM cmb@bcm.edu; sekar@broadinstitute.org; rader@mail.med.upenn.edu RI Buxbaum, Sarah/E-1970-2013; OI Buxbaum, Sarah/0000-0002-4886-3564; Cupples, L. Adrienne/0000-0003-0273-7965 FU T32 grant in Cell and Molecular Training for Cardiovascular Biology from the National Heart, Lung, and Blood Institute [K99-HL098364]; University of Virginia [R01-HL-071205] FX The following nine parent studies have contributed parent study data, ancillary study data, and DNA samples through the Broad Institute of Massachusetts Institute of Technology and Harvard (N01-HC-65226): Atherosclerosis Risk in Communities: University of North Carolina at Chapel Hill (N01-HC-55015, N01-HC-55018), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022); Cardiovascular Health Study: University of Washington (N01-HC-85079, N01-HC-55222, U01-HL-080295), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081, N01-HC-15103), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), University of Wisconsin (N01-HC-75150); Cleveland Family Study: Case Western Reserve University (R01-HL-46380, M01-RR-00080); Cooperative Study of Sickle Cell Disease: University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc., (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St.; Jude's Children's Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults: University of Alabama at Birmingham (N01-HC-48047, N01-HC-95095), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-University of California Los Angeles Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100) ;Framingham Heart Study: Boston University (N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321); Jackson Heart Study: Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis: University of Washington (N01-HC-95159), University of California, Los Angeles (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-University of California Los Angeles Research and Education Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205), University of Virginia (subcontract to R01-HL-071205); Sleep Heart Health Study: Johns Hopkins University (U01-HL-064360), Case Western University (U01-HL-063463), University of California, Davis (U01-HL-053916), University of Arizona (U01-HL-053938, U01-HL-053934), University of Pittsburgh (U01-HL-077813), Boston University (U01-HL-053941), MedStar Research Institute (U01-HL-063429), Johns Hopkins University (U01-HL-053937). This work was also supported in part by a T32 grant in Cell and Molecular Training for Cardiovascular Biology and K99-HL098364 from the National Heart, Lung, and Blood Institute (KM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 19 TC 13 Z9 13 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 21 PY 2012 VL 7 IS 5 AR e36473 DI 10.1371/journal.pone.0036473 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959VD UT WOS:000305343100005 PM 22629316 ER PT J AU Song, YH Tai, JHY Bartsch, SM Zimmerman, RK Muder, RR Lee, BY AF Song, Yeohan Tai, Julie H. Y. Bartsch, Sarah M. Zimmerman, Richard K. Muder, Robert R. Lee, Bruce Y. TI The potential economic value of a Staphylococcus aureus vaccine among hemodialysis patients SO VACCINE LA English DT Article DE Staphylococcus aureus; Vaccine; Economics; Hemodialysis; Cost-effectiveness ID COST-EFFECTIVENESS ANALYSIS; LONG-TERM HEMODIALYSIS; METHICILLIN-RESISTANT; CLINICAL-OUTCOMES; CONJUGATE VACCINE; RISK-FACTORS; BACTEREMIA; MANAGEMENT; INFECTION; DIALYSIS AB Staphylococcus aureus infections are a substantial problem for hemodialysis patients. Several vaccine candidates are currently under development, with hemodialysis patients being one possible target population. To determine the potential economic value of an S. aureus vaccine among hemodialysis patients, we developed a Markov decision analytic computer simulation model. When S. aureus colonization prevalence was 1%, the incremental cost-effectiveness ratio (ICER) of vaccination was <=$25,217/quality-adjusted life year (QALY). Vaccination became more cost-effective as colonization prevalence, vaccine efficacy, or vaccine protection duration increased or vaccine cost decreased. Even at 10% colonization prevalence, a 25% efficacious vaccine costing $100 prevented 29 infections, 21 infection-related hospitalizations, and 9 inpatient deaths per 1000 vaccinated HD patients. Our results suggest that an S. aureus vaccine would be cost-effective (i.e., ICERs <= $50,000/QALY) among hemodialysis patients over a wide range of S. aureus prevalence, vaccine costs and efficacies, and vaccine protection durations and delineate potential target parameters for such a vaccine. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Lee, Bruce Y.] Univ Pittsburgh, Publ Hlth Computat & Operat Res Grp, Publ Hlth Computat & Operat Res PHICOR, Pittsburgh, PA 15213 USA. [Song, Yeohan; Tai, Julie H. Y.; Bartsch, Sarah M.; Lee, Bruce Y.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15260 USA. [Song, Yeohan; Tai, Julie H. Y.; Bartsch, Sarah M.; Lee, Bruce Y.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zimmerman, Richard K.] Univ Pittsburgh, Sch Med, Dept Family Med, Pittsburgh, PA 15261 USA. [Muder, Robert R.] VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15240 USA. RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res Grp, Publ Hlth Computat & Operat Res PHICOR, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM ysongmd@umich.edu; juliehy@pitt.edu; smm168@pitt.edu; zimmrk@upmc.edu; robert.muder@va.gov; BYL1@pitt.edu OI Zimmerman, Richard/0000-0001-5941-6092 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [5U54GM088491-02]; Pennsylvania Department of Health (DOH) [4100047864] FX This work was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) grant 5U54GM088491-02 and the Pennsylvania Department of Health (DOH) grant 4100047864. The funders 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. NR 78 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 21 PY 2012 VL 30 IS 24 BP 3675 EP 3682 DI 10.1016/j.vaccine.2012.03.031 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 951SY UT WOS:000304741500024 PM 22464963 ER PT J AU Dowdell, SJ Clasie, B Depauw, N Metcalfe, P Rosenfeld, AB Kooy, HM Flanz, JB Paganetti, H AF Dowdell, Stephen J. Clasie, Benjamin Depauw, Nicolas Metcalfe, Peter Rosenfeld, Anatoly B. Kooy, Hanne M. Flanz, Jacob B. Paganetti, Harald TI Monte Carlo study of the potential reduction in out-of-field dose using a patient-specific aperture in pencil beam scanning proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DISTRIBUTIONS; DOSIMETRY; DELIVERY; TOOLKIT AB This study is aimed at identifying the potential benefits of using a patient-specific aperture in proton beam scanning. For this purpose, an accurate Monte Carlo model of the pencil beam scanning (PBS) proton therapy (PT) treatment head at Massachusetts General Hospital (MGH) was developed based on an existing model of the passive double-scattering (DS) system. The Monte Carlo code specifies the treatment head at MGH with sub-millimeter accuracy. The code was configured based on the results of experimental measurements performed at MGH. This model was then used to compare out-of-field doses in simulated DS treatments and PBS treatments. For the conditions explored, the penumbra in PBS is wider than in DS, leading to higher absorbed doses and equivalent doses adjacent to the primary field edge. For lateral distances greater than 10 cm from the field edge, the doses in PBS appear to be lower than those observed for DS. We found that placing a patient-specific aperture at nozzle exit during PBS treatments can potentially reduce doses lateral to the primary radiation field by over an order of magnitude. In conclusion, using a patient-specific aperture has the potential to further improve the normal tissue sparing capabilities of PBS. C1 [Dowdell, Stephen J.; Depauw, Nicolas; Metcalfe, Peter; Rosenfeld, Anatoly B.] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW 2522, Australia. [Dowdell, Stephen J.; Clasie, Benjamin; Depauw, Nicolas; Kooy, Hanne M.; Flanz, Jacob B.; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Dowdell, Stephen J.; Clasie, Benjamin; Depauw, Nicolas; Kooy, Hanne M.; Flanz, Jacob B.; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dowdell, SJ (reprint author), Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW 2522, Australia. EM sdowdell@partners.org RI Rosenfeld, Anatoly/D-1989-2014; Metcalfe, Peter/D-4040-2014 OI Metcalfe, Peter/0000-0002-6820-0055 FU Australian Rotary Health and the Rotary Clubs of Riverside; Cancer Institute of NSW; NIH/NCI [R01 CA140735] FX One of the authors (SJD) acknowledges financial support from Australian Rotary Health and the Rotary Clubs of Riverside. One of the authors (PM) acknowledges support from the Cancer Institute of NSW Clinical Leaders Program. One of the authors (HP) was in part funded by NIH/NCI R01 CA140735. NR 23 TC 19 Z9 19 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 21 PY 2012 VL 57 IS 10 BP 2829 EP 2842 DI 10.1088/0031-9155/57/10/2829 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 937SD UT WOS:000303677900003 PM 22513726 ER PT J AU Jia, ZK Wang, JX Yang, JJ Xue, R Zhang, D Wang, GN Ma, SL Duan, ZF AF Jia Zhan-kui Wang Jia-xiang Yang Jin-jian Xue Rui Zhang Da Wang Guan-nan Ma Sheng-li Duan Zhen-feng TI Discovery and identification of serum biomarkers of Wilms' tumor in mice using proteomics technology SO CHINESE MEDICAL JOURNAL LA English DT Article DE proteomics; Wilms' tumor; biomarker ID HUMAN APOLIPOPROTEIN(A); CANCER; SURVIVAL; PLASMINOGEN; EXPRESSION; CARCINOMA; PATHWAY; APOE AB Background Wilms' tumor (nephroblastoma) is a cancer of the kidneys that occurs typically in children and rarely in adults. Early diagnosis is very important for the treatment and prognosis of the disease. The aim of our study was to discover and identify potential non-invasive and convenient biomarkers for the diagnosis of Wilms' tumor. Methods Nude mice were used to construct a Wilms' tumor model by injecting nephroblastoma cells into their bilateral abdomen. We collected 94 serum samples from mice consisting of 45 samples with Wilms' tumor and 49 controls. The serum proteomic profiles of the samples were analyzed via surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The candidate biomarkers were purified by high-performance liquid chromatography, identified by liquid chromatography mass spectrometry, and validated using ProteinChip immunoassays. Results We finally retrieved two differential proteins (m/z 4509.2; 6207.9), which were identified as apolipoprotein A-II and polyubiquitin, respectively. The expression of apolipoprotein A-II was higher in the Wilms' tumor group than in the control group (P <0.01). By contrast, the expression of polyubiquitin was lower in the Wilms' tumor group than in the control group. Conclusion Apolipoprotein A-II and polyubiquitin may be used as potential biomarkers for nephroblastoma in children, and the analysis of apolipoprotein A-II may help diagnose and treat Wilms' tumor. C1 [Wang Jia-xiang; Zhang Da] Zhengzhou Univ, Affiliated Hosp 1, Dept Pediat Surg, Zhengzhou 450052, Henan, Peoples R China. [Jia Zhan-kui; Yang Jin-jian; Xue Rui] Zhengzhou Univ, Affiliated Hosp 1, Dept Urol Surg, Zhengzhou 450052, Henan, Peoples R China. [Wang Guan-nan] Zhengzhou Univ, Affiliated Hosp 1, Dept Pathol, Zhengzhou 450052, Henan, Peoples R China. [Ma Sheng-li] Second Hosp Kaifeng City, Dept Orthoped Surg, Kaifeng 475002, Henan, Peoples R China. [Duan Zhen-feng] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02138 USA. RP Wang, JX (reprint author), Zhengzhou Univ, Affiliated Hosp 1, Dept Pediat Surg, Zhengzhou 450052, Henan, Peoples R China. EM wangjiaxiang@126.com FU National Natural Science Foundation of China [81071782]; Institution of Higher Education [200804590004] FX This work was supported by grants from the National Natural Science Foundation of China (No. 81071782) and the Institution of Higher Education Specialized Research Fund for Doctor (No. 200804590004). NR 31 TC 1 Z9 1 U1 2 U2 2 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD MAY 20 PY 2012 VL 125 IS 10 BP 1727 EP 1732 DI 10.3760/cma.j.issn.0366-6999.2012.10.009 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 958RX UT WOS:000305259500009 PM 22800891 ER PT J AU Strother, DR London, WB Schmidt, ML Brodeur, GM Shimada, H Thorner, P Collins, MH Tagge, E Adkins, S Reynolds, CP Murray, K Lavey, RS Matthay, KK Castleberry, R Maris, JM Cohn, SL AF Strother, Douglas R. London, Wendy B. Schmidt, Mary Lou Brodeur, Garrett M. Shimada, Hiroyuki Thorner, Paul Collins, Margaret H. Tagge, Edward Adkins, Stanton Reynolds, C. Patrick Murray, Kevin Lavey, Robert S. Matthay, Katherine K. Castleberry, Robert Maris, John M. Cohn, Susan L. TI Outcome After Surgery Alone or With Restricted Use of Chemotherapy for Patients With Low-Risk Neuroblastoma: Results of Children's Oncology Group Study P9641 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXPRESSION-BASED CLASSIFICATION; NEURO-BLASTOMA; INFANTS; STAGE; THERAPY; STRATIFICATION; CRITERIA; BIOLOGY AB Purpose The primary objective of Children's Oncology Group study P9641 was to demonstrate that surgery alone would achieve 3-year overall survival (OS) >= 95% for patients with asymptomatic International Neuroblastoma Staging System stages 2a and 2b neuroblastoma (NBL). Secondary objectives focused on other low-risk patients with NBL and on those who required chemotherapy according to protocol-defined criteria. Patients and Methods Patients underwent maximally safe resection of tumor. Chemotherapy was reserved for patients with, or at risk for, symptomatic disease, with less than 50% tumor resection at diagnosis, or with unresectable progressive disease after surgery alone. Results For all 915 eligible patients, 5-year event-free survival (EFS) and OS were 89% +/- 1% and 97% +/- 1%, respectively. For patients with asymptomatic stage 2a or 2b disease, 5-year EFS and OS were 87% +/- 2% and 96% +/- 1%, respectively. Among patients with stage 2b disease, EFS and OS were significantly lower for those with unfavorable histology or diploid tumors, and OS was significantly lower for those >= 18 months old. For patients with stage 1 and 4s NBL, 5-year OS rates were 99% +/- 1% and 91% +/- 1%, respectively. Patients who required chemotherapy at diagnosis achieved 5-year OS of 98% +/- 1%. Of all patients observed after surgery, 11.1% experienced recurrence or progression of disease. Conclusion Excellent survival rates can be achieved in asymptomatic low-risk patients with stages 2a and 2b NBL after surgery alone. Immediate use of chemotherapy may be restricted to a minority of patients with low-risk NBL. Patients with stage 2b disease who are older or have diploid or unfavorable histology tumors fare less well. Future studies will seek to refine risk classification. J Clin Oncol 30:1842-1848. (c) 2012 by American Society of Clinical Oncology C1 [Strother, Douglas R.] Alberta Childrens Prov Gen Hosp, Calgary, AB T3B 6A8, Canada. [Strother, Douglas R.] Univ Calgary, Calgary, AB, Canada. [Thorner, Paul] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Thorner, Paul] Univ Toronto, Toronto, ON, Canada. [London, Wendy B.] Childrens Hosp, Childrens Oncol Grp Stat, Boston, MA 02115 USA. [London, Wendy B.] Childrens Hosp, Ctr Data, Boston, MA 02115 USA. [London, Wendy B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schmidt, Mary Lou] Univ Illinois, Chicago Coll Med, Chicago, IL 60680 USA. [Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA. [Brodeur, Garrett M.; Maris, John M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Shimada, Hiroyuki] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Matthay, Katherine K.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Collins, Margaret H.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Tagge, Edward] Univ S Carolina, Charleston, SC USA. [Adkins, Stanton] S Carolina Canc Ctr, Columbia, SC USA. [Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr Amarillo, Lubbock, TX 79409 USA. [Murray, Kevin] Hall Radiat Ctr, Cedar Rapids, IA USA. [Lavey, Robert S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Castleberry, Robert] Univ Alabama Birmingham, Birmingham, AL USA. RP Strother, DR (reprint author), Alberta Childrens Prov Gen Hosp, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM doug.strother@albertahealthservices.ca OI Reynolds, C. Patrick/0000-0002-2827-8536; Cohn, Susan/0000-0001-5749-7650 FU National Institutes of Health [U10-CA98543, U10-CA29139, U10 CA98413] FX Supported by National Institutes of Health Grants No. U10-CA98543, U10-CA29139, and U10 CA98413 to the Children's Oncology Group. NR 23 TC 28 Z9 35 U1 2 U2 6 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 MAY 20 PY 2012 VL 30 IS 15 BP 1842 EP 1848 DI 10.1200/JCO.2011.37.9990 PG 7 WC Oncology SC Oncology GA 947JZ UT WOS:000304427600020 PM 22529259 ER PT J AU Tap, WD Demetri, G Barnette, P Desai, J Kavan, P Tozer, R Benedetto, PW Friberg, G Deng, HJ McCaffery, I Leitch, I Badola, S Chang, S Zhu, M Tolcher, A AF Tap, William D. Demetri, George Barnette, Phillip Desai, Jayesh Kavan, Petr Tozer, Richard Benedetto, Pasquale W. Friberg, Gregory Deng, Hongjie McCaffery, Ian Leitch, Ian Badola, Sunita Chang, Sung Zhu, Min Tolcher, Anthony TI Phase II Study of Ganitumab, a Fully Human Anti-Type-1 Insulin-Like Growth Factor Receptor Antibody, in Patients With Metastatic Ewing Family Tumors or Desmoplastic Small Round Cell Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; SARCOMA FAMILY; GENE-EXPRESSION; FUSION PROTEIN; CANCER; RECURRENT; SURVIVAL; R1507; CT AB Purpose Ganitumab is a fully human monoclonal antibody against type-1 insulin-like growth factor receptor (IGF1R). An open-label phase II study was conducted to evaluate the efficacy and safety of ganitumab monotherapy in patients with metastatic Ewing family tumors (EFT) or desmoplastic small round cell tumors (DSRCT). Patients and Methods Patients >= 16 years of age with relapsed or refractory EFT or DSRCT received 12 mg/kg of ganitumab every 2 weeks. Objective response rate (ORR) was the primary end point. Secondary end points included clinical benefit rate (CBR = complete + partial responses + stable disease [SD] >= 24 weeks) and safety and pharmacokinetic profiles of ganitumab. The relationship between tumor response and EWS gene translocation status and IGF-1 levels was evaluated. Results Thirty-eight patients (22 with EFT; 16 with DSRCT) received one or more doses of ganitumab. Twenty-four patients (63%) experienced ganitumab-related adverse events. Grade 3 related events included hyperglycemia (n = 2), thrombocytopenia (n = 5), neutropenia (n = 2), leukopenia (n = 1), and transient ischemic attack (n = 1). There were no grade 4 or 5 treatment-related events. Of 35 patients assessed for response, two had partial responses (ORR, 6%) and 17 (49%) had SD. Four patients had SD >= 24 weeks, contributing to a CBR of 17%. The pharmacokinetic profile of ganitumab was similar to that observed in the first-in-human trial. Elevation of IGF-1 levels was observed postdose. EWS-Fli1 translocations were analyzed by RNA sequencing and fluorescent in situ hybridization, and novel translocations were observed in EFT and DSCRT. No apparent relationship between tumor response and IGF-1 levels or EWS gene translocations was observed. Conclusion Ganitumab was well tolerated and demonstrated antitumor activity in patients with advanced recurrent EFT or DSRCT. J Clin Oncol 30:1849-1856. (c) 2012 by American Society of Clinical Oncology C1 [Tap, William D.] Univ Calif Los Angeles, Los Angeles Med Ctr, Los Angeles, CA USA. [Friberg, Gregory; Deng, Hongjie; McCaffery, Ian; Leitch, Ian; Badola, Sunita; Zhu, Min] Amgen Inc, Thousand Oaks, CA USA. [Demetri, George] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Barnette, Phillip] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Desai, Jayesh] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Kavan, Petr] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Tozer, Richard] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada. [Benedetto, Pasquale W.] Univ Miami Sylvester, Ctr Comprehens Canc, Miami, FL USA. [Badola, Sunita] Amgen Inc, Cambridge, MA USA. [Tolcher, Anthony] START, San Antonio, TX USA. RP Tap, WD (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM tapw@mskcc.org FU Amgen; Pfizer; Ariad; Johnson Johnson; PharmaMar; Infinity Pharmaceuticals; Daiichi-Sankyo; Bristol-Myers Squibb; Genentech; OrthoBiotech; Schering-Plough Research Institute; Biogen Idec; ArQule; Bayer; Merck; Novartis; Array BioPharma FX Supported by Amgen.; Employment or Leadership Position: Gregory Friberg, Amgen (C); Hongjie Deng, Amgen (C); Ian McCaffery, Amgen (C); Ian Leitch, Amgen (C); Sunita Badola, Amgen (C); Sung Chang, Amgen (C); Min Zhu, Amgen (C) Consultant or Advisory Role: George Demetri, Amgen (C), Novartis (C), Pfizer (C), Ariad (C), Johnson & Johnson (C), PharmaMar (C), Genentech (C), Infinity Pharmaceuticals (C), EMD-Serono (C), GlaxoSmithKline (C), Daiichi-Sankyo (C), ArQule (C); Anthony Tolcher, Abraxis (C), Amgen (C), Exelixis (C), Genentech (C), GlaxoSmithKline (C), Merck (C), Pfizer (C), Biogen Idec (C), Novartis (C), Regeneron Pharmaceuticals (C), Ariad Pharmaceuticals (C), OrthoBiotec (C) Stock Ownership: Pasquale W. Benedetto, Amgen; Gregory Friberg, Amgen; Hongjie Deng, Amgen; Ian McCaffery, Amgen; Ian Leitch, Amgen; Sunita Badola, Amgen; Sung Chang, Amgen; Min Zhu, Amgen Honoraria: George Demetri, Novartis, Pfizer Research Funding: George Demetri, Pfizer, Ariad, Johnson & Johnson, PharmaMar, Infinity Pharmaceuticals, Amgen, Daiichi-Sankyo; Pasquale W. Benedetto, Amgen; Anthony Tolcher, Amgen, Bristol-Myers Squibb, Genentech, Pfizer, OrthoBiotech, Schering-Plough Research Institute, Biogen Idec, ArQule, Bayer, Merck, Novartis, Array BioPharma Expert Testimony: George Demetri, Ariad (U), Johnson & Johnson (U), PharmaMar (U) Other Remuneration: None NR 21 TC 72 Z9 73 U1 0 U2 7 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 MAY 20 PY 2012 VL 30 IS 15 BP 1849 EP 1856 DI 10.1200/JCO.2011.37.2359 PG 8 WC Oncology SC Oncology GA 947JZ UT WOS:000304427600021 PM 22508822 ER PT J AU Metzger, O Tutt, A de Azambuja, E Saini, KS Viale, G Loi, S Bradbury, I Bliss, JM Azim, HA Ellis, P Di Leo, A Baselga, J Sotiriou, C Piccart-Gebhart, M AF Metzger-Filho, Otto Tutt, Andrew de Azambuja, Evandro Saini, Kamal S. Viale, Giuseppe Loi, Sherene Bradbury, Ian Bliss, Judith M. Azim, Hatem A., Jr. Ellis, Paul Di Leo, Angelo Baselga, Jose Sotiriou, Christos Piccart-Gebhart, Martine TI Dissecting the Heterogeneity of Triple-Negative Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID INVASIVE DUCTAL CARCINOMA; BASAL-LIKE PHENOTYPE; LONG-TERM SURVIVAL; ESTROGEN-RECEPTOR; POLY(ADP-RIBOSE) POLYMERASE; MOLECULAR SUBTYPES; SPORADIC BREAST; NEOADJUVANT CHEMOTHERAPY; CYTOKERATIN EXPRESSION; EPITHELIAL PHENOTYPE AB Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers. It is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. TNBC is associated with a significantly higher probability of relapse and poorer overall survival in the first few years after diagnosis when compared with other breast cancer subtypes. This is observed despite its usual high sensitivity to chemotherapy. In the advanced setting, responses observed with chemotherapy lack durability. Early-stage clinical studies suggested impressive potential when a poly (ADP-ribose) polymerase (PARP) inhibitor is given for the treatment of advanced TNBC with BRCA gene dysfunction. The molecular complexity of TNBC has led to proposed subclassifications, which will be of great value for the development of targeted therapies. In this review, we discuss the biology of TNBC at the pathologic and the molecular levels. We also elaborate on the role of systemic therapies and the results of the first phase III clinical trial evaluating the addition of iniparib, a novel investigational anticancer agent that does not possess characteristics typical of the PARP inhibitor class, in combination with chemotherapy in advanced TNBC. J Clin Oncol 30:1879-1887. (c) 2012 by American Society of Clinical Oncology C1 [Metzger-Filho, Otto; de Azambuja, Evandro; Saini, Kamal S.; Loi, Sherene; Azim, Hatem A., Jr.; Sotiriou, Christos; Piccart-Gebhart, Martine] Univ Libre Brussels, Inst Jules Bordet, B-1000 Brussels, Belgium. [Tutt, Andrew; Ellis, Paul] Kings Coll London, London, England. [Bliss, Judith M.] Inst Canc Res, Sutton, Surrey, England. [Bradbury, Ian] Frontier Sci, Kincraig, Scotland. [Viale, Giuseppe] Univ Milan, European Inst Oncol, Milan, Italy. [Di Leo, Angelo] Hosp Prato, Prato, Italy. [Baselga, Jose] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Piccart-Gebhart, M (reprint author), Univ Libre Brussels, 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 sanofi-aventis; AstraZeneca FX Employment or Leadership Position: None Consultant or Advisory Role: Andrew Tutt, sanofi-aventis (U), AstraZeneca (U), Eisai (C), Clovis (C); Judith M. Bliss, sanofi-aventis (U); Hatem A. Azim Jr, Celgene (C); Paul Ellis, Roche (C), GlaxoSmithKline (C), sanofi-aventis (C), Esai (C); Angelo Di Leo, AstraZeneca (C), Pfizer (C), sanofi-aventis (C); Jose Baselga, sanofi-aventis (C); Martine Piccart-Gebhart, sanofi-aventis (C), Amgen (C), Roche (C), GlaxoSmithKline (C), PharmaMar (C) Stock Ownership: None Honoraria: Andrew Tutt, AstraZeneca, sanofi-aventis; Paul Ellis, Roche, Esai, sanofi-aventis; Angelo Di Leo, AstraZeneca, Pfizer, sanofi-aventis; Martine Piccart-Gebhart, sanofi-aventis, Amgen, Roche, GlaxoSmithKline, PharmaMar Research Funding: Andrew Tutt, sanofi-aventis; Judith M. Bliss, sanofi-aventis; Angelo Di Leo, AstraZeneca Expert Testimony: None Other Remuneration: Andrew Tutt, AstraZeneca, sanofi-aventis; Judith M. Bliss, sanofi-aventis NR 126 TC 158 Z9 169 U1 14 U2 51 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 MAY 20 PY 2012 VL 30 IS 15 BP 1879 EP 1887 DI 10.1200/JCO.2011.38.2010 PG 9 WC Oncology SC Oncology GA 947JZ UT WOS:000304427600025 PM 22454417 ER PT J AU Mayer, EL Gropper, AB Neville, BA Partridge, AH Cameron, DB Winer, EP Earle, CC AF Mayer, Erica L. Gropper, Adrienne B. Neville, Bridget A. Partridge, Ann H. Cameron, Danielle B. Winer, Eric P. Earle, Craig C. TI Follow-Up of Breast Cancer Survivors Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID PRIMARY-CARE; RANDOMIZED-TRIAL; SPECIALIST CARE; PATIENT C1 [Mayer, Erica L.; Neville, Bridget A.; Partridge, Ann H.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gropper, Adrienne B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cameron, Danielle B.] Univ Miami, Miller Sch Med, Boca Raton, FL USA. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Mayer, EL (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 BP 1893 EP 1894 DI 10.1200/JCO.2012.42.1339 PG 3 WC Oncology SC Oncology GA 947JZ UT WOS:000304427600029 ER PT J AU Abbas, KS Li, A Rivero, G Mitsiades, N Yellapragada, S AF Abbas, Kanza S. Li, Ang Rivero, Gustavo Mitsiades, Nicholas Yellapragada, Sarvari TI Survival outcome of veterans with myelodysplastic syndrome (MDS) treated with statins. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Baylor Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Dan L Duncan Canc Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e17018 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801859 ER PT J AU Abel, GA Lee, S Stone, RM Steensma, DP Young, N Houk, A Hastings, BT Martins, Y Klaassen, R AF Abel, Gregory Alan Lee, Stephanie Stone, Richard M. Steensma, David P. Young, Nancy Houk, Alice Hastings, B. Taylor Martins, Yolanda Klaassen, Robert TI Development of a disease-specific measure of quality of life in myelodysplastic syndromes (MDS): The "QUALMS-1". SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Laurentian Univ, Sudbury, ON P3E 2C6, Canada. Aplast Anemia & MDS Int Fdn, Rockville, MD USA. Univ Ottawa, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 6103 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804010 ER PT J AU Abrams, TA Meyer, G Moloney, J Meyerhardt, JA Schrag, D Fuchs, CS AF Abrams, Thomas Adam Meyer, Gary Moloney, Julie Meyerhardt, Jeffrey A. Schrag, Deborah Fuchs, Charles S. TI Patterns of chemotherapy (CT) use in a US-wide population-based cohort of patients (pts) with metastatic colorectal cancer (mCRC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. IntrinsiQ LLC, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3537 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804812 ER PT J AU Ackerman, A McDermott, DF Lawrence, DP Gunturi, A Flaherty, KT Giobbie-Hurder, A Hodi, FS Ibrahim, N Atkins, MB Cho, DC Sullivan, RJ AF Ackerman, Allison McDermott, David F. Lawrence, Donald P. Gunturi, Anasuya Flaherty, Keith T. Giobbie-Hurder, Anita Hodi, F. Stephen Ibrahim, Nageatte Atkins, Michael B. Cho, Daniel C. Sullivan, Ryan J. TI Outcomes of patients with malignant melanoma treated with immunotherapy prior to or after vemurafenib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8569 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801678 ER PT J AU Alexander, BM Wen, PY Lee, EQ Batchelor, T Cloughesy, TF Parmigiani, G Trippa, L AF Alexander, Brian Michael Wen, Patrick Y. Lee, Eudocia Quant Batchelor, Tracy Cloughesy, Timothy Francis Parmigiani, Giovanni Trippa, Lorenzo TI Bayesian adaptive randomized trial design for patients with recurrent glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2005 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801469 ER PT J AU Ali, SM Zubritsky, L Jacobus, SJ Leitzel, K Regan, MM Nakabayashi, M Knight, RD Laadem, A Sherman, ML Lipton, A Kantoff, P AF Ali, Suhail M. Zubritsky, Lindsey Jacobus, Susanna J. Leitzel, Kim Regan, Meredith M. Nakabayashi, Mari Knight, Robert D. Laadem, Abderrahmane Sherman, Matthew L. Lipton, Allan Kantoff, Philip TI Elevated serum activin A and survival in CRPC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Penn State Hershey Med Ctr, Hershey, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Celgene Corp, Summit, NJ USA. Acceleron Pharma, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15170 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803136 ER PT J AU Alsina, M Tabernero, J Shapiro, G Burris, H Infante, JR Weiss, GJ Cervantes-Ruiperez, A Gounder, MM Paz-Ares, L Falzone, R Hill, J Cehelsky, J Vaishnaw, A Gollob, J LoRusso, P AF Alsina, Maria Tabernero, Josep Shapiro, Geoffrey Burris, Howard Infante, Jeffrey R. Weiss, Glen J. Cervantes-Ruiperez, Andres Gounder, Mrinal M. Paz-Ares, Luis Falzone, Rick Hill, Jamie Cehelsky, Jeffrey Vaishnaw, Akshay Gollob, Jared LoRusso, Patricia TI Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Vall dHebron Univ Hosp, Mol Therapeut Res Unit, Barcelona, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Sarah Cannon Res Inst, Nashville, TN USA. Scottsdale Healthcare, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. Univ Valencia, INCLIVA, Dept Hematol & Med Oncol, Valencia, Spain. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Hosp Virgen del Rocio, Seville, Spain. Alnylam Pharmaceut, Cambridge, MA USA. Karmanos Canc Inst, Detroit, MI USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 3062 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802301 ER PT J AU Alsina, M Schlossman, RL Weber, DM Coutre, SE Lonial, S Gasparetto, C Warsi, G Ondovik, MS Mukhopadhyay, S Paley, CS Richardson, PGG AF Alsina, Melissa Schlossman, Robert L. Weber, Donna M. Coutre, Steven E. Lonial, Sagar Gasparetto, Cristina Warsi, Ghulam Ondovik, Michael S. Mukhopadhyay, Sutapa Paley, Carole S. Richardson, Paul Gerard Guy TI PANORAMA 2: A phase II study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Durham, NC USA. Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8012 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803836 ER PT J AU Altwairgi, AK Parulekar, W Chapman, JAW Shepherd, LE Pritchard, KI Han, L Goss, PE Whelan, TJ AF Altwairgi, Abdullah Khalaf Parulekar, Wendy Chapman, Judy-Anne W. Shepherd, Lois E. Pritchard, Kathleen I. Han, Lei Goss, Paul Edward Whelan, Timothy Joseph CA NCIC Clinical Trials Grp TI Impact of concurrent (CON) and sequential (SEQ) radiotherapy (RT) with adjuvant aromatase inhibitors (AI) in early-stage breast cancer (EBC): NCIC CTG MA.27. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Hamilton Hlth Sci, Juravinski Canc Ctr, Hamilton, ON, Canada. RI Whelan, Timothy/D-3185-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 500 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800176 ER PT J AU Amrein, PC Attar, EC Fathi, AT McAfee, SL Wadleigh, M DeAngelo, DJ Steensma, DP Foster, J Stone, RM Neuberg, DS Ballen, KK AF Amrein, Philip C. Attar, Eyal C. Fathi, Amir Tahmasb McAfee, Steven L. Wadleigh, Martha DeAngelo, Daniel J. Steensma, David P. Foster, Julia Stone, Richard M. Neuberg, Donna S. Ballen, Karen K. CA Massachusetts Gen Hosp TI Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6621 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800701 ER PT J AU Apolo, AB Philips, G Ostrovnaya, I Rosenberg, JE Milowsky, MI Small, EJ Bajorin, DF Halabi, S AF Apolo, Andrea Borghese Philips, George Ostrovnaya, Irina Rosenberg, Jonathan E. Milowsky, Matthew I. Small, Eric Jay Bajorin, Dean F. Halabi, Susan TI External validation of prognostic models for overall survival (OS) in patients (pts) with advanced cancer (UC) treated with cisplatin-based chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4592 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803088 ER PT J AU Arteaga, CL Mayer, IA O'Neill, AM Swaby, RF Alpaugh, RK Yang, XMJ Wagner, LI Meropol, NJ Saphner, TJ Jahanzeb, M Perez, EA Lin, NU Sledge, GW AF Arteaga, Carlos L. Mayer, Ingrid A. O'Neill, Anne M. Swaby, Ramona F. Alpaugh, R. Katherine Yang, Ximing J. Wagner, Lynne I. Meropol, Neal J. Saphner, Thomas James Jahanzeb, Mohammad Perez, Edith A. Lin, Nancy U. Sledge, George W. TI A randomized phase III double-blinded placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-overexpressing metastatic breast cancer (HER2+MBC): A trial of the Eastern Cooperative Oncology Group (E1105) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Vanderbilt Univ, Nashville, TN USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Chicago, IL 60611 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Green Bay Oncol, Green Bay, WI USA. Univ Miami, Sylvester Comprehens Canc Ctr, Coral Gables, FL 33124 USA. Mayo Clin, Jacksonville, FL 32224 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 605 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800386 ER PT J AU Attar, EC Johnson, JL Amrein, PC Lozanski, G Wadleigh, M DeAngelo, DJ Kolitz, JE Powell, BL Voorhees, PM Wang, ES Blum, WG Marcucci, G Bloomfield, CD Moser, BK Stone, RM Larson, RA AF Attar, Eyal C. Johnson, Jeffrey L. Amrein, Philip C. Lozanski, Gerard Wadleigh, Martha DeAngelo, Daniel J. Kolitz, Jonathan E. Powell, Bayard L. Voorhees, Peter Michael Wang, Eunice S. Blum, William G. Marcucci, Guido Bloomfield, Clara D. Moser, Barry K. Stone, Richard M. Larson, Richard A. CA CALGB TI A phase II study of bortezomib added to standard daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine (Int-DAC) for consolidation in patients with previously untreated acute myeloid leukemia (AML) age 60-75 years: CALGB study 10502. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Canc Stat Ctr, Durham, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hofstra North Shore LIJ Sch Med, Lake Success, NY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ N Carolina, Chapel Hill, NC USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Chicago, Chicago, IL 60637 USA. RI Blum, William/E-2769-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6526 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800142 ER PT J AU Azaro, A Baselga, J Sepulveda, JM Seoane, J Ahnert, JR Brana, I Gueorguieva, I Cleverly, A Lahn, MMF Pillay, S Paz-Ares, L Holdhoff, M Blakeley, JO Carducci, MA AF Azaro, Analia Baselga, Jose Sepulveda, Juan Manuel Seoane, Joan Ahnert, Jordi Rodon Brana, Irene Gueorguieva, Ivelina Cleverly, Ann Lahn, Michael M. F. Pillay, Sada Paz-Ares, Luis Holdhoff, Matthias Blakeley, Jaishri O'Neill Carducci, Michael Anthony TI The oral transforming growth factor-beta (TGF-beta) receptor I kinase inhibitor LY2157299 plus lomustine in patients with treatment-refractory malignant glioma: The first human dose study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. Vall dHebron Univ Hosp, Inst Oncol, Barcelona, Spain. Vall dHebron Univ Hosp, Mol Therapeut Res Unit, Barcelona, Spain. Vall dHebron Univ Hosp, Barcelona, Spain. Eli Lilly & Co, Indianapolis, IN 46285 USA. Eli Lilly & Co, Div Early Phase Oncol Clin Invest, Indianapolis, IN 46285 USA. Univ Hosp Virgen del Rocio, Seville, Spain. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2042 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801506 ER PT J AU Badve, SS Gray, RJ Baehner, FL Solin, LJ Butler, SM Yoshizawa, C Shak, S Hughes, LL Page, DL Sledge, GW Davidson, NE Perez, EA Ingle, JN Wood, WC Sparano, JA AF Badve, Sunil S. Gray, Robert James Baehner, Frederick L. Solin, Lawrence J. Butler, Steven M. Yoshizawa, Carl Shak, Steven Hughes, Lorie L. Page, David L. Sledge, George W. Davidson, Nancy E. Perez, Edith A. Ingle, James N. Wood, William C. Sparano, Joseph A. TI Correlation between the DCIS score and traditional clinicopathologic features in the prospectively designed E5194 clinical validation study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Indiana Univ Sch Med, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genom Hlth, Redwood City, CA USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Hope Ctr, Cartersville, GA USA. Vanderbilt Univ, Nashville, TN USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin, Rochester, MN USA. Emory Univ, Dept Surg, Atlanta, GA 30322 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1005 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800722 ER PT J AU Balmana, J Tung, NM Isakoff, SJ Grana, B Ryan, PD Rafi, R Tracy, M Winer, E Baselga, J Garber, JE AF Balmana, Judith Tung, Nadine M. Isakoff, Steven J. Grana, Begona Ryan, Paula D. Rafi, Rezvan Tracy, Michael Winer, Eric Baselga, Jose Garber, Judy Ellen TI Phase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Vall dHebron Univ Hosp, Barcelona, Spain. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. AstraZeneca, Wilmington, DE USA. AstraZeneca, Macclesfield, Cheshire, England. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1009 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800723 ER PT J AU Bandman, O Delcayre, A Laus, R Godfrey, WR Kantoff, PW Schlom, J Gulley, JL AF Bandman, Olga Delcayre, Alain Laus, Reiner Godfrey, Wayne Russell Kantoff, Philip W. Schlom, Jeffrey Gulley, James L. TI Prospect: A randomized, double-blind, phase III efficacy trial of PROSTVAC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 BN ImmunoTherapeut, Mountain View, CA USA. Bavarian Nord Immunotherapeut, Mountain View, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4699 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803319 ER PT J AU Bao, T Betts, K Tarpinian, K Cai, L Gould, J Jeter, S Medeiros, M Tait, N Chumsri, S Armstrong, DK Bardia, A Tan, MT Stebbing, J Kelleher, WP Folkerd, E Dowsett, M Singh, H Snyder, CF Tkaczuk, KH Stearns, V AF Bao, Ting Betts, Kelly Tarpinian, Karineh Cai, Ling Gould, Jeff Jeter, Stacie Medeiros, Michelle Tait, Nancy Chumsri, Saranya Armstrong, Deborah Kay Bardia, Aditya Tan, Ming Tony Stebbing, Justin Kelleher, William Peter Folkerd, Elizabeth Dowsett, Mitchell Singh, Harvinder Snyder, Claire Frances Tkaczuk, Katherine Hanna Stearns, Vered TI Changes in patient-reported outcomes in women with breast cancer in a multicenter double-blind randomized controlled trial assessing the effect of acupuncture in reducing aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Maryland, Baltimore, MD 21201 USA. Greenebaum Canc Ctr, Baltimore, MD USA. Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Imperial Coll Healthcare NHS Trust, London, England. Univ London Imperial Coll Sci Technol & Med, London, England. Inst Canc Res, Sutton, Surrey, England. Royal Marsden Hosp, London SW3 6JJ, England. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 9103 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804534 ER PT J AU Barnholt, KE Do, CB Kiefer, AK Nelson, M Garber, JE Robson, ME Maki, RG Demetri, GD Wojcicki, A AF Barnholt, Kimberly E. Do, Chuong B. Kiefer, Amy K. Nelson, Marisa Garber, Judy Ellen Robson, Mark E. Maki, Robert G. Demetri, George D. Wojcicki, Anne TI Genome-wide analysis and characterization of an online sarcoma cohort SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 23andMe Inc, Mountain View, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mt Sinai Sch Med, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 10097 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801206 ER PT J AU Baselga, J Cortes, J Im, SA Pivot, XB Clark, E Knott, A Ross, G Swain, SM AF Baselga, Jose Cortes, Javier Im, Seock-Ah Pivot, Xavier B. Clark, Emma Knott, Adam Ross, Graham Swain, Sandra M. TI Adverse events with pertuzumab and trastuzumab: Evolution during treatment with and without docetaxel in CLEOPATRA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Vall dHebron Univ Hosp, Dept Oncol, Barcelona, Spain. Seoul Natl Univ, Coll Med, Dept Internal Med, Div Hematol Med Oncol, Seoul, South Korea. CHU Jean Minjoz, Besancon, France. Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. NR 0 TC 3 Z9 3 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 597 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800010 ER PT J AU Beck, JT Rugo, HS Burris, HA Baselga, J Noguchi, S Gnant, M Pritchard, KI Bennett, L Ricci, JF Hortobagyi, GN AF Beck, J. Thaddeus Rugo, Hope S. Burris, Howard A. Baselga, Jose Noguchi, Shinzaburo Gnant, Michael Pritchard, Kathleen I. Bennett, Lee Ricci, Jean-Francois Hortobagyi, Gabriel N. TI BOLERO-2: Health-related quality-of-life in metastatic breast cancer patients treated with everolimus and exemestane versus exemestane SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Highlands Oncol Grp, Fayetteville, AR USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Sarah Cannon Res Inst, Nashville, TN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. Med Univ Vienna, Dept Surg, Ctr Comprehens Canc, Vienna, Austria. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. RTI Hlth Solut, Res Triangle Pk, NC USA. Wellmera AG, Basel, Switzerland. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 539 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800366 ER PT J AU Berry, DL Hong, FX Halpenny, B Wang, Q Partridge, AH Fann, JR Wolpin, S Lober, WB Bush, N Bosco, JLF Parvathaneni, U Amtmann, D Back, A AF Berry, Donna Lynn Hong, Fangxin Halpenny, Barbara Wang, Qian Partridge, Ann H. Fann, Jesse R. Wolpin, Seth Lober, William B. Bush, Nigel Bosco, Jaclyn Lee Fong Parvathaneni, Upendra Amtmann, Dagmar Back, Anthony TI Electronic self-report assessment for cancer: Results of a multisite randomized trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98195 USA. Seattle Canc Care Alliance, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9008 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803173 ER PT J AU Blackwell, KL Miles, D Gianni, L Krop, IE Welslau, M Baselga, J Pegram, MD Oh, DY Dieras, V Olsen, SR Fang, L Lu, MW Guardino, E Verma, S AF Blackwell, Kimberly L. Miles, David Gianni, Luca Krop, Ian E. Welslau, Manfred Baselga, Jose Pegram, Mark D. Do-Youn Oh Dieras, Veronique Olsen, Steven R. Fang, Liang Lu, Michael W. Guardino, Ellie Verma, Sunil TI Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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 C1 Duke Univ, Med Ctr, Durham, NC USA. Mt Vernon Canc Ctr, Middlesex, England. Hosp San Raffaele, I-20132 Milan, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Inst Curie, Dept Med Oncol, Paris, France. Genentech Inc, San Francisco, CA 94080 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. NR 0 TC 5 Z9 5 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA LBA1 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803703 ER PT J AU Blay, JY Leahy, MG Nguyen, BB Patel, S Santoro, A Hohenberger, P Demetri, GD Lardelli, P Perez, I Chawla, SP AF Blay, Jean-Yves Leahy, Michael Gordon Binh Bui Nguyen Patel, Shreyaskumar Santoro, Armando Hohenberger, Peter Demetri, George D. Lardelli, Pilar Perez, Iratxe Chawla, Sant P. TI Randomized multicenter phase III trial of trabectedin (T) versus doxorubicin-based chemotherapy as first-line therapy in patients with translocation-related sarcoma (TRS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Ctr Leon Berard, F-69373 Lyon, France. Christie NHS Fdn Trust, Manchester, Lancs, England. Inst Bergonie, Bordeaux, France. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Ist Clin Humanitas IRCCS, Humanitas Canc Ctr, Rozzano, Italy. Univ Klinikum Mannheim, Mannheim, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. PharmaMar, Madrid, Spain. Sarcoma Oncol Ctr, Santa Monica, CA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS10101 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801542 ER PT J AU Blay, JY Chawla, SP Ray-Coquard, I Le Cesne, A Staddon, AP Milhem, MM Penel, N Riedel, RF Nguyen, BB Cranmer, LD Reichardt, P Bompas, E Alcindor, T Rushing, DA Song, Y Ebbinghaus, S Haluska, FG Dodion, PF Demetri, GD AF Blay, Jean-Yves Chawla, Sant P. Ray-Coquard, Isabelle Le Cesne, Axel Staddon, Arthur P. Milhem, Mohammed M. Penel, Nicolas Riedel, Richard F. Binh Bui Nguyen Cranmer, Lee D. Reichardt, Peter Bompas, Emmanuelle Alcindor, Thierry Rushing, Daniel A. Song, Yang Ebbinghaus, Scot Haluska, Frank G. Dodion, Pierre F. Demetri, George D. TI Phase III, placebo-controlled trial (SUCCEED) evaluating ridaforolimus as maintenance therapy in advanced sarcoma patients following clinical benefit from prior standard cytotoxic chemotherapy: Long-term (>= 24 months) overall survival results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. Sarcoma Oncol Ctr, Santa Monica, CA USA. Ctr Leon Berard, F-69373 Lyon, France. Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. Univ Penn, Philadelphia, PA 19104 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Ctr Oscar Lambret, F-59020 Lille, France. Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. Inst Bergonie, Bordeaux, France. Univ Arizona, Ctr Canc, Tucson, AZ USA. HELIOS Klinikum Bad Saarow, Bad Saarow Pieskow, Germany. Ctr Rene Gauducheau, F-44035 Nantes, France. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Indiana Univ, Indianapolis, IN 46204 USA. Merck & Co Inc, Whitehouse Stn, NJ USA. Merck Res Labs, N Wales, PA USA. ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10010 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801327 ER PT J AU Bobiak, S Choti, MA Benson, AB Strosberg, JR Bloomston, M Bergsland, EK Zornosa, CC Kulke, M Nakakura, EK Shah, MH Yao, JC AF Bobiak, Sarah Choti, Michael A. Benson, Al B. Strosberg, Jonathan R. Bloomston, Mark Bergsland, Emily K. Zornosa, Carrie C. Kulke, Matthew Nakakura, Eric K. Shah, Manisha H. Yao, James C. TI Description of initial treatment for newly diagnosed metastatic carcinoid (cNET) and pancreatic neuroendocrine (pNET) patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Natl Comprehens Canc Network, Ft Washington, PA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. Solove Res Inst, Columbus, OH USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Bloomston, Mark/E-2767-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e14542 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804889 ER PT J AU Boyer, MJ Janne, PA Mok, T O'Byrne, KJ Paz-Ares, LG Ramalingam, SS Liang, JQ Taylor, I Campbell, A O'Connell, JP Letrent, SP Antic, V AF Boyer, Michael J. Janne, Pasi A. Mok, Tony O'Byrne, Kenneth John Paz-Ares, Luis G. Ramalingam, Suresh S. Liang, Jane Q. Taylor, Ian Campbell, Alicyn O'Connell, Joseph P. Letrent, Stephen P. Antic, Vladan TI ARCHER: Dacomitinib (D; PF-00299804) versus erlotinib (E) for advanced (adv) non-small cell lung cancer (NSCLC)-A randomized double-blind phase III study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Sydney Canc Ctr, Camperdown, NSW, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Chinese Univ Hong Kong, State Key Lab South China, Sha Tin, Hong Kong, Peoples R China. St James Hosp, Dublin, Ireland. Hosp Univ Virgen del Rocio, Seville, Spain. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Pfizer Oncol, Groton, CT USA. Pfizer Oncol, La Jolla, CA USA. Pfizer AG, Zurich, Switzerland. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS7615 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804169 ER PT J AU Boyle, F Smith, IE O'Shaughnessy, J Ejlertsen, B Kaufmann, M Buzdar, A Fumoleau, P Gradishar, WJ Martin, M Moy, B Piccart-Gebhart, MJ Pritchard, KI Lindquist, D Amonkar, M Huang, YJ Williams, LS Wang, Q Finkelstein, DM Goss, PE AF Boyle, Frances Smith, Ian Edward O'Shaughnessy, Joyce Ejlertsen, Bent Kaufmann, Manfred Buzdar, Aman Fumoleau, Pierre Gradishar, William John Martin, Miguel Moy, Beverly Piccart-Gebhart, Martine J. Pritchard, Kathleen I. Lindquist, Deborah Amonkar, Mayur Huang, Yingjie Williams, Lisa Simone Wang, Qing Finkelstein, Dianne M. Goss, Paul Edward TI Lapatinib in HER2+early breast cancer: Quality of life analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mater Hosp, Sydney, NSW, Australia. Royal Marsden Hosp, London SW3 6JJ, England. Baylor Sammons Canc Ctr, Dallas, TX USA. US Oncol, Dallas, TX USA. Rigshosp, DK-2100 Copenhagen, Denmark. Goethe Univ Frankfurt, D-60054 Frankfurt, Germany. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Ctr Georges Francois Leclerc, Dijon, France. Northwestern Univ, Chicago, IL 60611 USA. Hosp Univ Gregorio Maranon, Madrid, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Arizona Oncol, Sedona, AZ USA. US Oncol, Sedona, AZ USA. GlaxoSmithKline, Collegeville, PA USA. GlaxoSmithKline, Uxbridge, Middx, England. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 604 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800016 ER PT J AU Bradbury, AR Moy, B Peppercorn, JM Egleston, B Sands, CB Sheikh-Salah, M Storm, CD Helft, PR AF Bradbury, Angela R. Moy, Beverly Peppercorn, Jeffrey M. Egleston, Brian Sands, Colleen B. Sheikh-Salah, Moktar Storm, Courtney D. Helft, Paul R. TI Financial relationships with commercial interests (COI) among abstracts at the ASCO Annual Meeting SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. ASCO, Alexandria, VA USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6128 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800341 ER PT J AU Brahmer, JR Horn, L Antonia, S Spigel, DR Gandhi, L Sequist, LV Wigginton, J McDonald, D Kollia, G Gupta, AK Gettinger, SN AF Brahmer, Julie R. Horn, Leora Antonia, Scott Spigel, David R. Gandhi, Leena Sequist, Lecia V. Wigginton, Jon McDonald, Dan Kollia, Georgia Gupta, Ashok Kumar Gettinger, Scott N. TI Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. SCRI Tennessee Oncol PLLC, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Bristol Myers Squibb Co, Princeton, NJ USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 8 Z9 9 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7509 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804176 ER PT J AU Brastianos, PK Horowitz, P Santagata, S Jones, RT McKenna, A Ligon, K Palescandolo, E Van Hummelen, P Getz, G Hahn, WC Dunn, IF Beroukhim, R AF Brastianos, Priscilla Kaliopi Horowitz, Peleg Santagata, Sandro Jones, Robert T. McKenna, Aaron Ligon, Keith Palescandolo, Emanuele Van Hummelen, Paul Getz, Gad Hahn, William C. Dunn, Ian F. Beroukhim, Rameen TI Genomic characterization of meningiomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2020 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801373 ER PT J AU Brooks, G Li, L Sharma, DB Schrag, D AF Brooks, Gabriel Li, Ling Sharma, Dhruv B. Schrag, Deborah TI Regional variation in Medicare spending and survival among older adults with advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 [Brooks, Gabriel; Li, Ling; Sharma, Dhruv B.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6003 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802842 ER PT J AU Brown, JR Sharman, JP Harb, WA Kelly, KR Schreeder, MT Sweetenham, JW Barr, PM Foran, JM Gabrilove, JL Kipps, TJ Ma, S O'Brien, SM Evans, E Lounsbury, H Silver, BA Singh, J Stiede, K Westlin, W Witowski, S Mahadevan, D AF Brown, Jennifer R. Sharman, Jeff Porter Harb, Wael A. Kelly, Kevin R. Schreeder, Marshall T. Sweetenham, John W. Barr, Paul M. Foran, James M. Gabrilove, Janice Lynn Kipps, Thomas J. Ma, Shuo O'Brien, Susan Mary Evans, Erica Lounsbury, Heather Silver, Bruce A. Singh, Juswinder Stiede, Kathryn Westlin, William Witowski, Steven Mahadevan, Daruka TI Phase Ib trial of AVL-292, a covalent inhibitor of Bruton's tyrosine kinase (Btk), in chronic lymphocytic leukemia (CLL) and B-non-Hodgkin lymphoma (B-NHL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. US Oncol, Willamette Valley Canc Inst, Springfield, OR USA. Horizon Oncol Ctr, Lafayette, IN USA. Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA. Clearview Canc Inst, Huntsville, AL USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Mayo Clin, Ctr Canc, Jacksonville, FL 32224 USA. Mt Sinai Sch Med, New York, NY USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Avila Therapeut, Bedford, MA USA. Univ Arizona, Ctr Canc, Tucson, AZ USA. NR 0 TC 4 Z9 4 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 8032 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803716 ER PT J AU Bunnell, CA Gross, A Kalfin, M Partridge, AH Lane, S Burstein, HJ Fine, B Hilton, N Sullivan, C Colicchio, L Hagemeister, E Kelly, A Szabatura, A Winer, E Mann, S Weingart, S AF Bunnell, Craig A. Gross, Anne Kalfin, Michael Partridge, Ann H. Lane, Sharon Burstein, Harold J. Fine, Barbara Hilton, Nancy Sullivan, Clare Colicchio, Lynn Hagemeister, Erin Kelly, Anne Szabatura, Audrea Winer, Eric Mann, Susan Weingart, Saul TI Implementation of a team training program in the treatment of breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e16515 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801124 ER PT J AU Butaney, M Porter, J Lindeman, NI Janne, PA Rabin, MS Marcoux, JP Johnson, BE Jackman, DM AF Butaney, Mohit Porter, Jennifer Lindeman, Neal Ian Janne, Pasi A. Rabin, Michael S. Marcoux, J. Paul Johnson, Bruce E. Jackman, David Michael TI Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7588 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804386 ER PT J AU Cahill, DP Beiko, J Suki, D Prabhu, SS Weinberg, J Lang, FF Gilbert, MR Rao, G McCutcheon, IE Aldape, KD Sawaya, R AF Cahill, Daniel P. Beiko, Jason Suki, Dima Prabhu, Sujit S. Weinberg, Jeffrey Lang, Frederick F. Gilbert, Mark R. Rao, Ganesh McCutcheon, Ian E. Aldape, Kenneth D. Sawaya, Raymond TI IDH1 status and survival benefit from surgical resection of enhancing and nonenhancing tumor in malignant astrocytomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Manitoba, Winnipeg, MB, Canada. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2019 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801566 ER PT J AU Capelletti, M Lipson, D Otto, G Yelensky, R Ercan, D Kim, J Sasaki, H Kim, HR Park, SI Ross, JS Stephens, P Cronin, MT Janne, PA AF Capelletti, Marzia Lipson, Doron Otto, Geoff Yelensky, Roman Ercan, Dalia Kim, Jhingook Sasaki, Hidefumi Kim, Hyeong Ryul Park, Seung-Il Ross, Jeffrey S. Stephens, Philip Cronin, Maureen T. Janne, Pasi Antero TI Discovery of recurrent KIF5B-RET fusions and other targetable alterations from clinical NSCLC specimens SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Fdn Med, Cambridge, MA USA. Fdn Med Inc, Cambridge, MA USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. Nagoya City Univ, Grad Sch Med, Nagoya, Aichi, Japan. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Thorac Surg, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7510 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804329 ER PT J AU Carvajal, RD Chugh, R Milhem, MM Ryan, CW George, S Chmielowski, B Agulnik, M Rodler, ET Elias, AD Budd, GT Tawbi, H Movva, S Van Tine, BA Dickson, MA Hensley, ML Keohan, ML Tap, WD Bennett, CM Maki, RG Schwartz, GK AF Carvajal, Richard D. Chugh, Rashmi Milhem, Mohammed M. Ryan, Christopher W. George, Suzanne Chmielowski, Bartosz Agulnik, Mark Rodler, Eve T. Elias, Anthony D. Budd, G. Thomas Tawbi, Hussein Movva, Sujana Van Tine, Brian Andrew Dickson, Mark Andrew Hensley, Martee Leigh Keohan, Mary Louise Tap, William D. Bennett, Cathryn M. Maki, Robert G. Schwartz, Gary K. TI Randomized multicenter double-blind phase II trial: The immunological adjuvant OPT-821 with or without a trivalent ganglioside vaccine in metastatic sarcoma patients following metastasectomy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Translat Oncol Res Lab, Los Angeles, CA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Seattle Canc Care Alliance, Seattle, WA USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Pittsburgh, Med Ctr Canc Pavil, Pittsburgh, PA USA. Wihship Canc Inst Emory Midtown, Atlanta, GA USA. Washington Univ, St Louis, MO USA. MabVax Therapeut Inc, San Diego, CA USA. Mt Sinai Sch Med, New York, NY USA. RI Movva, Sujana/I-3513-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS10103 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801583 ER PT J AU Cervantes-Ruiperez, A Juric, D Hidalgo, M Messersmith, WA Blumenschein, GR Baselga, J Perez, DR Dienstmann, R Calles, A Jimeno, A Sanabria, S Littman, C Amler, LC Pirzkall, A Tabernero, J AF Cervantes-Ruiperez, Andres Juric, Dejan Hidalgo, Manuel Messersmith, Wells A. Blumenschein, George R. Baselga, Jose Perez, Desamparados Roda Dienstmann, Rodrigo Calles, Antonio Jimeno, Antonio Sanabria, Sandra Littman, Catherine Amler, Lukas C. Pirzkall, Andrea Tabernero, Josep TI A phase I study of MEHD7945A (MEHD), a first-in-class HER3/EGFR dual-action antibody, in patients (pts) with refractory/recurrent epithelial tumors: Expansion cohorts. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Valencia, INCLIVA, Dept Hematol & Med Oncol, Valencia, Spain. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. START Madrid, Ctr Integral Oncol Clara Campal, Madrid, Spain. Univ Colorado, Aurora, CO USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Clin, Dept Med Oncol, Colorectal Unit, Dept Surg, Valencia, Spain. Vall dHebron Univ Hosp, Mol Therapeut Res Unit, Barcelona, Spain. Univ Colorado Denver, Div Med Oncol, Aurora, CO USA. Genentech Inc, San Francisco, CA 94080 USA. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. NR 0 TC 2 Z9 2 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2568 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801689 ER PT J AU Chapman, PB Hauschild, A Robert, C Larkin, JMG Haanen, JBAG Ribas, A Hogg, D Hamid, O Ascierto, PA Testori, A Lorigan, P Dummer, R Sosman, JA Garbe, C Maio, M Nolop, KB Nelson, BJ Joe, AK Flaherty, KT McArthur, GA AF Chapman, Paul B. Hauschild, Axel Robert, Caroline Larkin, James M. G. Haanen, John B. A. G. Ribas, Antoni Hogg, David Hamid, Omid Ascierto, Paolo Antonio Testori, Alessandro Lorigan, Paul Dummer, Reinhard Sosman, Jeffrey Alan Garbe, Claus Maio, Michele Nolop, Keith B. Nelson, Betty J. Joe, Andrew K. Flaherty, Keith T. McArthur, Grant A. TI Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAF(V600E)-mutated melanoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Klinikum Schleswig Holstein, Kiel Schleswig Holstein, Germany. Canc Inst Gustave Roussy, Villejuif, France. Royal Marsden Hosp, London SW3 6JJ, England. Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. Angeles Clin & Res Inst, Santa Monica, CA USA. Ist Nazl Tumori Fdn Pascale, Unit Med Oncol & Innovat Therapy, Naples, Italy. European Inst Oncol, Milan, Italy. Univ Manchester, Manchester, Lancs, England. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Tubingen, Tubingen, Germany. Univ Hosp Siena, Siena, Italy. Plexxikon Inc, Berkeley, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. RI Lorigan, Paul/J-6898-2015 OI Lorigan, Paul/0000-0002-8875-2164 NR 0 TC 38 Z9 38 U1 1 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8502 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800505 ER PT J AU Chodak, G Schellhammer, PF Whitmore, JB Sims, RB Kantoff, PW AF Chodak, Gerald Schellhammer, Paul F. Whitmore, James Boyd Sims, Robert Brownell Kantoff, Philip W. TI Overall survival (OS) benefit with sipuleucel-T by baseline PSA: An exploratory analysis from the phase III IMPACT trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Weiss Mem Hosp, Chicago, IL USA. Eastern Virginia Med Sch Urol Virginia, Norfolk, VA USA. Dendreon Corp, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4648 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802609 ER PT J AU Choti, MA Bobiak, S Strosberg, JR Benson, A Bloomston, M Yao, JC Zornosa, CC Bergsland, EK Kulke, M Nakakura, EK Shah, MH AF Choti, Michael A. Bobiak, Sarah Strosberg, Jonathan R. Benson, Al Bowen Bloomston, Mark Yao, James C. Zornosa, Carrie C. Bergsland, Emily K. Kulke, Matthew Nakakura, Eric K. Shah, Manisha H. TI Prevalence of functional tumors in neuroendocrine carcinoma: An analysis from the NCCN NET database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Natl Comprehens Canc Network, Ft Washington, PA USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. Solove Res Inst, Columbus, OH USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Bloomston, Mark/E-2767-2011 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4126 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800598 ER PT J AU Choueiri, TK Pal, SK McDermott, DF Ramies, DA Morrissey, S Lee, Y Miles, D Holland, J Dutcher, JP AF Choueiri, Toni K. Pal, Sumanta Kumar McDermott, David F. Ramies, David A. Morrissey, Stephanie Lee, Yihua Miles, Dale Holland, Jaymes Dutcher, Janice P. TI Efficacy of cabozantinib (XL184) in patients (pts) with metastatic, refractory renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. City Hope Natl Med Ctr, Duarte, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Exelixis, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 11 Z9 11 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 4504 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802872 ER PT J AU Clark, RM Growdon, WB Wiechert, A del Carmen, MG Goodman, A Boruta, DM Bradford, L Garrett, LA Schorge, JO AF Clark, Rachel Marie Growdon, Whitfield Board Wiechert, Andrew del Carmen, Marcela G. Goodman, Annekathryn Boruta, David M. Bradford, Leslie Garrett, Leslie A. Schorge, John O. TI Hospital readmission after surgical cytoreduction for epithelial ovarian carcinoma: An assessment of risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 [Clark, Rachel Marie; Growdon, Whitfield Board; Wiechert, Andrew; del Carmen, Marcela G.; Goodman, Annekathryn; Boruta, David M.; Bradford, Leslie; Garrett, Leslie A.; Schorge, John O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA e15545 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803471 ER PT J AU Cohen, SJ Feng, Y Landry, JC Staley, CA Whittington, R Sigurdson, ER Nimeiri, HS Verma, UN Benson, A AF Cohen, Steven J. Feng, Yang Landry, Jerome Carl Staley, Charles A. Whittington, Richard Sigurdson, Elin R. Nimeiri, Halla Sayed Verma, Udit N. Benson, Al Bowen TI Phase II study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: A trial of the Eastern Cooperative Oncology Group (E3204) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. VA Med Ctr, Philadelphia, PA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3605 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804673 ER PT J AU Corcoran, RB Falchook, GS Infante, JR Hamid, O Messersmith, WA Kwak, EL Ryan, DP Kurzrock, R Brenner, AA Luan, J Sun, P Allred, AJ Little, SM Patel, K Kopetz, S Venook, AP AF Corcoran, Ryan Bruce Falchook, Gerald Steven Infante, Jeffrey R. Hamid, Omid Messersmith, Wells A. Kwak, Eunice Lee Ryan, David P. Kurzrock, Razelle Brenner, Adrienne A. Luan, Jennifer Sun, Peng Allred, Alicia J. Little, Shonda M. Patel, Kiran Kopetz, Scott Venook, Alan Paul TI BRAF V600 mutant colorectal cancer (CRC) expansion cohort from the phase I/II clinical trial of BRAF inhibitor dabrafenib (GSK2118436) plus MEK inhibitor trametinib (GSK1120212) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA. Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. Angeles Clin & Res Inst, Dept Med Oncol, Los Angeles, CA USA. Univ Colorado, Dept Med Oncol, Aurora, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. GlaxoSmithKline, Collegeville, PA USA. Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 3528 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804562 ER PT J AU Corcoran, RB Falchook, GS Infante, JR Hamid, O Messersmith, WA Kwak, EL Ryan, DP Kurzrock, R Brenner, AA Luan, J Sun, P Allred, AJ Little, SM Patel, K Kopetz, S Venook, AP AF Corcoran, Ryan Bruce Falchook, Gerald Steven Infante, Jeffrey R. Hamid, Omid Messersmith, Wells A. Kwak, Eunice Lee Ryan, David P. Kurzrock, Razelle Brenner, Adrienne A. Luan, Jennifer Sun, Peng Allred, Alicia J. Little, Shonda M. Patel, Kiran Kopetz, Scott Venook, Alan Paul TI BRAF V600 mutant colorectal cancer (CRC) expansion cohort from the phase I/II clinical trial of BRAF inhibitor dabrafenib (GSK2118436) plus MEK inhibitor trametinib (GSK1120212). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA. Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. Angeles Clin & Res Inst, Dept Med Oncol, Los Angeles, CA USA. Univ Colorado, Dept Med Oncol, Aurora, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. GlaxoSmithKline, Collegeville, PA USA. Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3528 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802046 ER PT J AU Corless, CL Neff, T Heinrich, MC Beadling, C AF Corless, Christopher L. Neff, Tanaya Heinrich, Michael C. Beadling, Carol TI Combining semiconductor-based sequencing with amplicon-based cancer gene panels: A rapid next-gen approach to clinical cancer genotyping. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10591 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803550 ER PT J AU Cortes, J Baselga, J Im, YH Ross, G Clark, E Knott, A Swain, SM AF Cortes, Javier Baselga, Jose Im, Young-Hyuck Ross, Graham Clark, Emma Knott, Adam Swain, Sandra M. TI Quality of life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Vall dHebron Univ Hosp, Dept Oncol, Barcelona, Spain. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. NR 0 TC 2 Z9 2 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 598 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800205 ER PT J AU Cortes, JE Kim, DW Pinilla-Ibarz, J Paquette, R le Coutre, PD Chuah, C Nicolini, FE Apperley, J Khoury, HJ Talpaz, M DiPersio, JF DeAngelo, DJ Rea, D Abruzzese, E Muller, MC Baccarani, M Gambacorti-Passerini, C Turner, CD Haluska, FG Kantarjian, H AF Cortes, Jorge E. Kim, Dong-Wook Pinilla-Ibarz, Javier Paquette, Ronald le Coutre, Philipp D. Chuah, Charles Nicolini, Franck E. Apperley, Jane Khoury, Hanna Jean Talpaz, Moshe DiPersio, John F. DeAngelo, Daniel J. Rea, Delphine Abruzzese, Elisabetta Mueller, Martin C. Baccarani, Michele Gambacorti-Passerini, Carlo Turner, Christopher D. Haluska, Frank G. Kantarjian, Hagop TI PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph plus ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Catholic Univ Korea, Seoul, South Korea. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. Charite, D-13353 Berlin, Germany. Singapore Gen Hosp, Singapore, Singapore. Ctr Hosp Lyon Sud, Pierre Benite, France. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. Emory Winship Canc Inst, Atlanta, GA USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop St Louis, Serv Malad Sang, Paris, France. Osped S Eugenio, Rome, Italy. Heidelberg Univ, Med Fak Mannheim, Med Klin 3, Mannheim, Germany. Univ Hosp Bologna, Bologna, Italy. Univ Milano Bicocca, Azienda Osped San Gerardo, Unita Ric Clin Ematol, Monza, Italy. ARIAD Pharmaceut, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6503 PG 2 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801016 ER PT J AU D'Ambrosio, L Brusa, F D'Ascenzo, F Cavallero, E Biondi-Zoccai, G Boccone, P Bironzo, P Levin, GN Eckel, RH Milani, RV Sagalowsky, AI Gasparini, M Grignani, G Gaita, F Ciuffreda, L Aglietta, M AF D'Ambrosio, Lorenzo Brusa, Federica D'Ascenzo, Fabrizio Cavallero, Erica Biondi-Zoccai, Giuseppe Boccone, Paola Bironzo, Paolo Levin, Glenn N. Eckel, Robert H. Milani, Richard V. Sagalowsky, Arthur I. Gasparini, Mauro Grignani, Giovanni Gaita, Fiorenzo Ciuffreda, Libero Aglietta, Massimo TI Risk of adverse cardiovascular events (CVE) and incident diabetes mellitus (DM) in patients (pts) with prostate cancer (PC) treated with androgen deprivation therapy (ADT): A meta-analysis of adjusted observational results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Inst Canc Res & Treatment, Candiolo, Italy. Ctr Oncol & Ematol Subalpino, Turin, Italy. Univ Turin, Div Cardiol, Turin, Italy. Univ Modena & Reggio Emilia, Div Cardiol, Modena, Italy. Baylor Coll Med, Cardiac Care Unit, Houston, TX 77030 USA. Michael E DeBakey Med Ctr, Houston, TX USA. Univ Colorado, Aurora, CO USA. Ochsner Med Ctr, Div Cardiol, New Orleans, LA USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Politecn Torino, Dept Math, I-10128 Turin, Italy. Univ Turin, Div Cardiol, Corso Dogliotti, Italy. AOU S Giovanni Battista Molinette, Div Oncol, Turin, Italy. RI Milani, Richard/A-6045-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15192 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802859 ER PT J AU Luu, DCN Mamet, R Zornosa, CC Niland, JC D'Amico, TA Kalemkerian, GP Koczywas, M Pisters, K Rabin, MS Otterson, GA AF Dai Chu Nguyen Luu Mamet, Rizvan Zornosa, Carrie C. Niland, Joyce C. D'Amico, Thomas A. Kalemkerian, Gregory Peter Koczywas, Marianna Pisters, Katherine Rabin, Michael S. Otterson, Gregory Alan TI Retrospective analysis of the impact of age on overall survival in patients with non-small cell lung cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. City Hope Natl Med Ctr, Duarte, CA USA. Natl Comprehens Canc Network, Ft Washington, PA USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA e18018 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804097 ER PT J AU Dang, CT Gianni, L Romieu, G Dirix, L Campone, M Citron, ML Zamagni, C Krop, IE Xu, N Smitt, M Suter, T AF Dang, Chau T. Gianni, Luca Romieu, Gilles Dirix, Luc Campone, Mario Citron, Marc L. Zamagni, Claudio Krop, Ian E. Xu, Na Smitt, Melanie Suter, Thomas TI Cardiac safety in a phase II study of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as adjuvant or neoadjuvant therapy for early-stage HER2-positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Hosp San Raffaele, I-20132 Milan, Italy. CRLC Val dAurelle, Montpellier, France. Sint Augustinus Hosp, Brussels, Belgium. Inst Cancerol Ouest Rene Gauducheau, Nantes, France. Albert Einstein Coll Med, Lake Success, NY USA. St Orsola Marcello Malpighi Hosp, Addarii Med Oncol Unit, Bologna, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Hosp Bern, CH-3010 Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 532 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800125 ER PT J AU De Bono, JS Fizazi, K Saad, F Taplin, ME Sternberg, CN Miller, K Mulders, P Chi, KN Armstrong, AJ Hirmand, M Selby, B Scher, HI AF De Bono, Johann Sebastian Fizazi, Karim Saad, Fred Taplin, Mary-Ellen Sternberg, Cora N. Miller, Kurt Mulders, Peter Chi, Kim N. Armstrong, Andrew J. Hirmand, Mohammad Selby, Brian Scher, Howard I. CA AFFIRM Investigators TI Primary, secondary, and quality-of-life endpoint results from the phase III AFFIRM study of MDV3100, an androgen receptor signaling inhibitor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Inst Canc Res, London SW3 6JB, England. Univ Paris 11, Orsay, France. Univ Montreal Hosp Ctr, Montreal, PQ, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. San Camillo & Forlanini Hosp, Rome, Italy. Charite, D-13353 Berlin, Germany. Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. Medivation Inc, San Francisco, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Mulders, Peter/H-8076-2014 NR 0 TC 9 Z9 9 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 4519 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802767 ER PT J AU Demetri, GD Reichardt, P Kang, YK Blay, JY Joensuu, H Maki, RG Rutkowski, P Hohenberger, P Gelderblom, H Leahy, MG von Mehren, M Schoffski, P Blackstein, ME Le Cesne, A Badalamenti, G Xu, JM Nishida, T Laurent, D Kuss, I Casali, PG AF Demetri, George D. Reichardt, Peter Kang, Yoon-Koo Blay, Jean-Yves Joensuu, Heikki Maki, Robert G. Rutkowski, Piotr Hohenberger, Peter Gelderblom, Hans Leahy, Michael Gordon von Mehren, Margaret Schoffski, Patrick Blackstein, Martin E. Le Cesne, Axel Badalamenti, Giuseppe Xu, Jian-Ming Nishida, Toshirou Laurent, Dirk Kuss, Iris Casali, Paolo Giovanni CA GRID Invest TI Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. HELIOS Klinikum Bad Saarow, Bad Saarow Pieskow, Germany. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Univ Lyon 1, Ctr Leon Berard, F-69365 Lyon, France. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. Mt Sinai Sch Med, New York, NY USA. Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. Inst Oncol, Warsaw, Poland. Univ Mannheim, Med Ctr, Dept Surg, D-68131 Mannheim, Germany. Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. Christie NHS Fdn Trust, Manchester, Lancs, England. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Inst Gustave Roussy, Villejuif, France. Univ Palermo, Dept Oncol, Div Med Oncol, Palermo, Italy. Acad Mil Med Sci, Affiliated Hosp, Beijing, Peoples R China. Osaka Police Hosp, Dept Surg, Osaka, Japan. Bayer HealthCare Pharmaceut, Berlin, Germany. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA LBA10008 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801304 ER PT J AU Desai, P Braun, E Dehghan-Paz, I Gattuso, P Canar, J Cobleigh, MA AF Desai, Palak Braun, Eduardo Dehghan-Paz, Irene Gattuso, Paolo Canar, Jeff Cobleigh, Melody A. TI Synchronous bilateral breast cancer (SBBC): Concordance of receptor status between right and left breast SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Rush Univ, Natl Surg Adjuvant Breast & Bowel Project, Med Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 572 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800078 ER PT J AU Dimopoulos, MA Facon, T Richardson, PGG Orlowski, RZ San-Miguel, JF Lonial, S Anderson, KC Moreau, P Reece, DE Singhal, A Shazer, RL Kopit, J Palumbo, AP AF Dimopoulos, Meletios A. Facon, Thierry Richardson, Paul Gerard Guy Orlowski, Robert Z. San-Miguel, Jesus F. Lonial, Sagar Anderson, Kenneth Carl Moreau, Philippe Reece, Donna Ellen Singhal, Anil Shazer, Ronald L. Kopit, Justin Palumbo, Antonio Pierangelo TI ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Hellen Cooperat Oncol Grp, Athens, Greece. Hop Claude Huriez, Lille, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Hosp Univ Salamanca, Salamanca, Spain. Multiple Myeloma Res Consortium, Norwalk, CT USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Hosp, Nantes, France. Princess Margaret Hosp, Program Multiple Myeloma, Toronto, ON M4X 1K9, Canada. Abbott Biotherapeut, Redwood City, CA USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Univ Turin, Turin, Italy. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS8113 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804080 ER PT J AU Drake, CG Fishman, MN Curti, BD Kim, JJ Stadler, WM McNeel, DG Choueiri, TK Redman, B Hudes, GR Jure-Kunkel, M McDonald, D Gupta, AK Pathak, AK Wigginton, J Sznol, M AF Drake, Charles G. Fishman, Mayer N. Curti, Brendan D. Kim, Jenny J. Stadler, Walter Michael McNeel, Douglas G. Choueiri, Toni K. Redman, Bruce Hudes, Gary R. Jure-Kunkel, Maria McDonald, Dan Gupta, Ashok Kumar Pathak, Ashutosh Kumar Wigginton, Jon Sznol, Mario TI An exploratory study to investigate the immunomodulatory activity of BMS-936558 in patients with metastatic clear-cell renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. H Lee Moffitt Canc Canter & Res Inst, Tampa, FL USA. Providence Onc & Hem Clin, Portland, OR USA. Univ Chicago, Chicago, IL 60637 USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Yale Canc Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS2613 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802123 ER PT J AU Drapkin, BJ Sadrzadeh, H Brunner, AM Werner, L Babirak, L Attar, EC Ballen, KK McAfee, SL Amrein, PC Chen, YBA Stone, RM Fathi, AT AF Drapkin, Benjamin Jacob Sadrzadeh, Hossein Brunner, Andrew Mark Werner, Lillian Babirak, Loren Attar, Eyal C. Ballen, Karen K. McAfee, Steven L. Amrein, Philip C. Chen, Yi-Bin Albert Stone, Richard M. Fathi, Amir Tahmasb TI A seasonal pattern of presentation in younger patients with de novo acute myeloid leukemia (AML). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6617 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802366 ER PT J AU DuBois, SG Krailo, MD Gebhardt, MC Donaldson, SS Marcus, KC Dormans, JP Shamberger, RC Sailer, SL Nicholas, RW Healey, JH Tarbell, N Devidas, M Meyer, JS Granowetter, L Womer, R Bernstein, ML Marina, N Grier, HE AF DuBois, Steven G. Krailo, Mark D. Gebhardt, Mark C. Donaldson, Sarah S. Marcus, Karen Chayt Dormans, John P. Shamberger, Robert C. Sailer, Scott Lee Nicholas, Richard W. Healey, John H. Tarbell, Nancy Devidas, Meenakshi Meyer, James S. Granowetter, Linda Womer, Richard Bernstein, Mark L. Marina, Neyssa Grier, Holcombe E. TI Evaluation of local control strategies in patients with localized Ewing sarcoma of bone: A report from the Children's Oncology Group. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Oncol Grp, Arcadia, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Stanford Canc Ctr, Stanford, CA USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Canc Ctr N Carolina, Cary, NC USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Oncol Grp, Gainesville, FL USA. NYU, New York, NY USA. IWK Hlth Ctr, Halifax, NS, Canada. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9537 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802115 ER PT J AU Dueck, AC Mendoza, TR Mitchell, SA Reeve, BB Castro, KM Denicoff, A O'Mara, AM Rogak, LJ Clauser, SB Bryant, DM Gillis, TA Bearden, JD Siegel, RD Harness, JK Paul, DB Cleeland, CS Sloan, JA Schrag, D Minasian, LM Basch, EM AF Dueck, Amylou C. Mendoza, Tito R. Mitchell, Sandra A. Reeve, Bryce B. Castro, Kathleen M. Denicoff, Andrea O'Mara, Ann M. Rogak, Lauren J. Clauser, Steven B. Bryant, Donna M. Gillis, Theresa A. Bearden, James D. Siegel, Robert D. Harness, Jay K. Paul, Diane B. Cleeland, Charles S. Sloan, Jeff A. Schrag, Deborah Minasian, Lori M. Basch, Ethan M. TI Validity and reliability of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mayo Clin, Scottsdale, AZ USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. NCI, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Canc Program Our Lady Lake & Mary Bird Perkins, Baton Rouge, LA USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. Gibbs Canc Ctr, Spartanburg, SC USA. Hartford Hosp, Helen & Harry Gray Canc Ctr, Hartford, CT 06115 USA. St Joseph Hosp Orange, Ctr Canc Prevent & Treatment, Orange, CA USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9047 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804389 ER PT J AU Durie, BG Moreau, P Sonneveld, P Morgan, GJ Lahuerta, JJ Beksac, M Terpos, E Hajek, R Hungria, VTD Maiolino, A Chng, W Lee, JH Jian, H Richardson, PGG Chen, WM Knop, S Hoerring, A Leleu, X San-Miguel, JF Kumar, S AF Durie, Brian G. Moreau, Philippe Sonneveld, Pieter Morgan, Gareth J. Lahuerta, Juan Jose Beksac, Meral Terpos, Evangelos Hajek, Roman de Moraes Hungria, Vania Tietsche Maiolino, Angelo Chng, WeeJoo Lee, Jae Hoon Jian, Hou Richardson, Paul Gerard Guy Chen, Wenming Knop, Stefan Hoerring, Antje Leleu, Xavier San-Miguel, Jesus F. Kumar, Shaji CA Int Myeloma Working Grp TI Regional differences in the treatment approaches for relapsed multiple myeloma: An IMF study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. Univ Hosp Nantes, Nantes, France. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. Univ Hosp, Serv Hematol, Madrid, Spain. Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. Univ Athens, Athens, Greece. Univ Hosp Brno, Brno, Czech Republic. Irmandade Santa Casa de Misericordia Sao Paulo, Sao Paulo, Brazil. Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. Natl Univ Hlth Syst, Queenstown, Singapore. Gachon Univ Gil Hosp, Dept Internal Med, Inchon, South Korea. Shanghai Changzheng Hosp, Shanghai, Peoples R China. Dana Farber Canc Inst, Boston, MA 02115 USA. Beijing Chaoyang Hosp, Beijing, Peoples R China. Univ Wurzburg, D-97070 Wurzburg, Germany. Canc Res & Biostat, Seattle, WA USA. Hop Claude Huriez, Serv Malad Sang, Lille, France. Hosp Univ Salamanca, Salamanca, Spain. Mayo Clin, Rochester, MN USA. RI Kumar, Shaji/A-9853-2008; richard, chrystelle/K-8595-2015 OI Kumar, Shaji/0000-0001-5392-9284; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8095 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804019 ER PT J AU Edelman, MJ Tan, MT Fidler, MJ Sanborn, RE Otterson, GA Sequist, LV Evans, TL Schneider, BJ Keresztes, R Rogers, JS de Mayolo, JA Medeiros, M Zaknoen, SL AF Edelman, Martin J. Tan, Ming Tony Fidler, Mary J. Sanborn, Rachel E. Otterson, Gregory Alan Sequist, Lecia V. Evans, Tracey L. Schneider, Bryan J. Keresztes, Roger Rogers, John S. de Mayolo, Jorge Antunez Medeiros, Michelle Zaknoen, Sara L. TI A randomized, double-blind, placebo-controlled multicenter phase II study of the COX-2 inhibitor apricoxib (A) in combination with either docetaxel (doc) or pemetrexed (pem) in advanced non-small cell lung cancer (NSCLC) patients (pts) selected by urinary PGE-m suppression. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Providence Portland Med Ctr, Portland, OR USA. Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Weill Cornell Med Coll, New York, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. W Virginia Univ, Sch Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. Mercy Res Inst, Miami, FL USA. Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Tragara Pharmaceut, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7546 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804123 ER PT J AU Eisenberger, MA Kattan, MW Sternberg, CN De Wit, R Epstein, JI Ecstein-Fraisse, EB Kibel, AS AF Eisenberger, Mario A. Kattan, Michael W. Sternberg, Cora N. De Wit, Ronald Epstein, Jonathan I. Ecstein-Fraisse, Evelyne B. Kibel, Adam Stuart TI A multinational phase III adjuvant study of immediate (I) versus deferred (D) chemotherapy (C)/hormone therapy (HT) after radical prostatectomy (RP): TAX-3501 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. San Camillo Hosp, Rome, Italy. Forlanini Hosp, Rome, Italy. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Johns Hopkins Sch Med, Baltimore, MD USA. Sanofi, Paris, France. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4570 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803347 ER PT J AU El-Jawahri, A Traeger, L Park, ER Greer, JA Pirl, WF Lennes, IT Jackson, VA Gallagher, ER Temel, JS AF El-Jawahri, Areej Traeger, Lara Park, Elyse R. Greer, Joseph A. Pirl, William F. Lennes, Inga Tolin Jackson, Vicki A. Gallagher, Emily R. Temel, Jennifer S. TI Advanced gastrointestinal cancer patients' perceptions of prognosis and goals of treatment. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6106 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802572 ER PT J AU Emadi, A Sadrzadeh, H Patal, P Burns, KH Duffield, A Ballen, KK Amrein, PC Attar, EC Smith, BD Fathi, AT AF Emadi, Ashkan Sadrzadeh, Hossein Patal, Payal Burns, Kathleen H. Duffield, Amy Ballen, Karen K. Amrein, Philip C. Attar, Eyal C. Smith, B. Douglas Fathi, Amir Tahmasb TI History of autoimmunity to predict clinical response to DNA methyltransferase inhibitors (DNMTI) in myelodysplastic syndromes (MDS), and MDS-derived acute myeloid leukemias (AML). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Johns Hopkins Univ, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6629 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801325 ER PT J AU Enzinger, PC Kwak, EL Szymonifka, J Abrams, TA Regan, E Malinowski, P Shih, KC Allen, JN Jackson, N Chan, JA Fidias, P Ryan, DP Fuchs, CS Bendell, JC AF Enzinger, Peter C. Kwak, Eunice Lee Szymonifka, Jackie Abrams, Thomas Adam Regan, Eileen Malinowski, Paige Shih, Kent C. Allen, Jill N. Jackson, Nadine Chan, Jennifer A. Fidias, Panos Ryan, David P. Fuchs, Charles S. Bendell, Johanna C. TI Multicenter randomized phase II trial of cisplatin, irinotecan plus bevacizumab (PCA) versus docetaxel, cisplatin, irinotecan plus bevacizumab (TPCA) in patients (pts) with metastatic esophagogastric cancer (MEGCA). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4027 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804121 ER PT J AU Epstein, AS Volandes, AE Gary, K Chen, LY Li, YL Agre, P Levin, T Reidy, DL Meng, RD Segal, NH Yu, KH Janjigian, YY Abou-Alfa, GK Kelsen, DP O'Reilly, EM AF Epstein, Andrew S. Volandes, Angelo E. Gary, Kristen Chen, Ling Y. Li, Yuelin Agre, Pat Levin, Tomer Reidy, Diane Lauren Meng, Raymond D. Segal, Neil Howard Yu, Kenneth H. Janjigian, Yelena Yuriy Abou-Alfa, Ghassan K. Kelsen, David Paul O'Reilly, Eileen Mary TI A randomized trial of a cardiopulmonary resuscitation (CPR) video (V) in advance care planning (ACP) for progressive hepatopancreaticobiliary cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mt Sinai, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9105 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800365 ER PT J AU Epstein-Peterson, Z Sullivan, A Phelps, AC Balboni, MJ Vanderweele, TJ Balboni, TA AF Epstein-Peterson, Zachary Sullivan, Adam Phelps, Andrea C. Balboni, Michael J. Vanderweele, Tyler J. Balboni, Tracy A. TI Spiritual care provided by oncology physicians and nurses to advanced cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9116 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804298 ER PT J AU Epstein-Peterson, Z Sullivan, A Phelps, AC Balboni, MJ Vanderweele, TJ Balboni, TA AF Epstein-Peterson, Zachary Sullivan, Adam Phelps, Andrea C. Balboni, Michael J. Vanderweele, Tyler J. Balboni, Tracy A. TI Spiritual care provided by oncology physicians and nurses to advanced cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9116 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804099 ER PT J AU Etchin, J Kentsis, A Sanda, T Kung, AL Stone, RM McCauley, D Kauffman, M Shacham, S Look, AT AF Etchin, Julia Kentsis, Alex Sanda, Takaomi Kung, Andrew L. Stone, Richard M. McCauley, Dilara Kauffman, Michael Shacham, Sharon Look, A. Thomas TI Evaluation of KPT-SINE (Selective Inhibitors of CRM1-Mediated Nuclear Export) in AML and T-ALL. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Karyopharm Therapeut, Boston, MA USA. Karyopharm Therapeut, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e13586 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802569 ER PT J AU Ewer, M Baselga, J Clark, E Benyunes, M Ross, G Swain, SM AF Ewer, Michael Baselga, Jose Clark, Emma Benyunes, Mark Ross, Graham Swain, Sandra M. TI Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in the CLEOPATRA study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. Genentech Inc, San Francisco, CA 94080 USA. MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 533 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800327 ER PT J AU Fakhro, SA Jennings, D Pinho, MC Lin, NU Sorensen, AG Batchelor, T Gerstner, ER AF Fakhro, Summer A. Jennings, Dominique Pinho, Marco C. Lin, Nancy U. Sorensen, A. Gregory Batchelor, Tracy Gerstner, Elizabeth Robins TI Response of nonenhancing regions in glioblastoma to VEGF-signaling inhibitor cediranib correlates with tumor infiltration SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hop, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hop, Martinos Ctr Biomed Imaging, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Simemens Healthcare USA, Malvern, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 3036 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802550 ER PT J AU Faris, JE Hong, TS McDermott, S Borger, DR Guimaraes, AR Wo, JYL Sahani, D Dias, LE Allen, JN Zhu, AX Murphy, JE Kwak, EL Ryan, DP Clark, JW Blaszkowsky, LS AF Faris, Jason Edward Hong, Theodore S. McDermott, Shaunagh Borger, Darrell R. Guimaraes, Alexander R. Wo, Jennifer Yon-Li Sahani, Dushyant Dias, Lauren Elizabeth Allen, Jill N. Zhu, Andrew X. Murphy, Janet E. Kwak, Eunice Lee Ryan, David P. Clark, Jeffrey W. Blaszkowsky, Lawrence Scott TI FOLFIRINOX in locally advanced and metastatic pancreatic cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. North Shore Canc Ctr, Danvers, MA USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e14615 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801437 ER PT J AU Fathi, AT Abdel-Wahab, OI Sadrzadeh, H Foster, J Burke, M Borger, DR Iafrate, AJ Adamia, S Liu, SY Ballen, KK Amrein, PC Attar, EC Straley, K Yen, K Schenkein, DP Neuberg, DS Levine, RL Chen, YBA Stone, RM AF Fathi, Amir Tahmasb Abdel-Wahab, Omar Ibrahim Sadrzadeh, Hossein Foster, Julia Burke, Meghan Borger, Darrell R. Iafrate, A. John Adamia, Sophia Liu, Suiyang Ballen, Karen K. Amrein, Philip C. Attar, Eyal C. Straley, Kimberly Yen, Katharine Schenkein, David P. Neuberg, Donna S. Levine, Ross L. Chen, Yi-Bin Albert Stone, Richard M. TI Prospective evaluation of serial 2-hydroxyglutarate in acute myeloid leukemia (AML) to determine response to therapy and predict relapse SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Agios Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6606 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802662 ER PT J AU Fiore, M Coppola, S Colombo, C Bertagnolli, MM George, S Le Cesne, A Casali, PG Gronchi, A Bonvalot, S Raut, CP AF Fiore, Marco Coppola, Sara Colombo, Chiara Bertagnolli, Monica M. George, Suzanne Le Cesne, Axel Casali, Paolo Giovanni Gronchi, Alessandro Bonvalot, Sylvie Raut, Chandrajit P. TI Desmoid fibromatosis and pregnancy: A multi-institutional analysis of recurrence and obstetric risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Inst Gustave Roussy, Villejuif, France. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10017 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800372 ER PT J AU Fisch, M Zhao, FM O'Mara, AM Wang, XS Cella, D Cleeland, CS AF Fisch, Michael Zhao, Fengmin O'Mara, Ann M. Wang, Xin Shelley Cella, David Cleeland, Charles S. CA Eastern Cooperative Oncology Grp TI Determinants of fatigue improvement in outpatient oncology according to baseline categories of fatigue severity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 9112 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804287 ER PT J AU Fisch, M Zhao, FM O'Mara, AM Wang, XS Cella, D Cleeland, CS AF Fisch, Michael Zhao, Fengmin O'Mara, Ann M. Wang, Xin Shelley Cella, David Cleeland, Charles S. CA Eastern Cooperative Oncology Grp TI Determinants of fatigue improvement in outpatient oncology according to baseline categories of fatigue severity. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 9112 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804085 ER PT J AU Fizazi, K Massard, C Smith, MR Rader, ME Brown, JE Milecki, P Shore, ND Oudard, S Karsh, LI Carducci, MA Damiao, R Wang, H Goessl, CD AF Fizazi, Karim Massard, Christophe Smith, Matthew Raymond Rader, Michael E. Brown, Janet Elizabeth Milecki, Piotr Shore, Neal D. Oudard, Stephane Karsh, Lawrence Ivan Carducci, Michael Anthony Damiao, Ronaldo Wang, Huei Goessl, Carsten Dietrich TI Baseline covariates impacting overall survival (OS) in a phase III study of men with bone metastases from castration-resistant prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Inst Gustave Roussy, Villejuif, France. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Nyack Hosp, Nyack, NY USA. Canc Res UK Expt Canc Med Ctr, Leeds, W Yorkshire, England. Canc Res UK Expt Canc Med Ctr, Sheffield, S Yorkshire, England. Greater Poland Canc Ctr, Poznan, Poland. Med Univ, Poznan, Poland. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Georges Pompidou European Hosp, Paris, France. Urol Ctr Colorado, Denver, CO USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 4642 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803097 ER PT J AU Fletcher, KM Prigerson, HG Maciejewski, PK AF Fletcher, Kalen M. Prigerson, Holly Gwen Maciejewski, Paul K. TI Women know, and men wish they knew, prognostic information in advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9037 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800148 ER PT J AU Fougeray, R Choueiri, TK Pons, F Schutz, FAB Salhi, Y Rosenberg, JE Bellmunt, J AF Fougeray, Ronan Choueiri, Toni K. Pons, Francesc Schutz, Fabio Augusto Barros Salhi, Yacine Rosenberg, Jonathan E. Bellmunt, Joaquim TI Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Inst Rech Pierre Fabre, Boulogne, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Brigham & Womens Hos, Boston, MA 02115 USA. Univ Hosp del Mar IMIM, Dept Med Oncol, Barcelona, Spain. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15007 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803188 ER PT J AU Freedman, RA Virgo, KS Labadie, J Partridge, AH Keating, NL AF Freedman, Rachel A. Virgo, Katherine S. Labadie, Julia Partridge, Ann H. Keating, Nancy Lynn TI Receipt of locoregional therapy among young women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Canc Soc, Intramural Res Dept, Hlth Serv Res Program, Atlanta, GA 30329 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1100 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801032 ER PT J AU Galanina, N Sprecher, E Bossuyt, V Sarkar, S Krop, IE Winer, E Tuck, DP Bruce, C Harris, L AF Galanina, Natalie Sprecher, Emmet Bossuyt, Veerle Sarkar, Sudipa Krop, Ian E. Winer, Eric Tuck, David P. Bruce, Can Harris, Lyndsay TI Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Yale Univ Sch Med, Yale Comprehens Canc Ctr, New Haven, CT USA. Yale Univ Sch Med, New Haven, CT USA. Yale Comprehens Canc Ctr, Dept Pathol, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ Sch Med, Dept Pathol, New Haven, CT USA. Keck Bioinformat Resource, New Haven, CT USA. Case Western Seidman Canc Ctr, Cleveland, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10558 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804146 ER PT J AU Gandhi, L Heist, RS Lucca, JV Temel, JS Fidias, P Morse, LK Johnson, BE AF Gandhi, Leena Heist, Rebecca Suk Lucca, Joan Vern Temel, Jennifer S. Fidias, Panos Morse, Linda K. Johnson, Bruce E. TI A phase II trial of pazopanib in relapsed/refractory small cell lung cancer (SCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 7099 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802825 ER PT J AU Garg, M Lee, JY Kachnic, LA Catalano, PJ Henry, DH Cooley, TP Ratner, L Wachsman, W Aboulafia, DM Benson, AB Palefsky, J Whittington, R Mitsuyasu, RT Sparano, JA AF Garg, Madhur Lee, Jeanette Y. Kachnic, Lisa A. Catalano, Paul J. Henry, David H. Cooley, Timothy Patrick Ratner, Lee Wachsman, William Aboulafia, David Michael Benson, Al Bowen Palefsky, Joel Whittington, Richard Mitsuyasu, Ronald T. Sparano, Joseph A. TI Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): Safety and preliminary efficacy results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Yeshiva Univ Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10461 USA. Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. Boston Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Penn Hosp, Philadelphia, PA 19107 USA. Washington Univ, St Louis, MO USA. VASDHS, La Jolla, CA USA. UCSD Sch Med, La Jolla, CA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Philadelphia, PA USA. Univ Calif Los Angeles, Los Angeles Care Ctr, Los Angeles, CA USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 4030 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804686 ER PT J AU Garon, EB Moran, T Barlesi, F Gandhi, L Sequist, LV Kim, SW Groen, HJM Besse, B Smit, EF Kim, DW Akimov, M Avsar, E Bailey, S Felip, E AF Garon, Edward B. Moran, Teresa Barlesi, Fabrice Gandhi, Leena Sequist, Lecia V. Kim, Sang-We Groen, Harry J. M. Besse, Benjamin Smit, Egbert F. Kim, Dong-Wan Akimov, Mikhail Avsar, Emin Bailey, Stuart Felip, Enriqueta TI Phase II study of the HSP90 inhibitor AUY922 in patients with previously treated, advanced non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Hosp Germans, Catalan Inst Oncol, Barcelona, Spain. Aix Marseille Univ, Marseille, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Asan Med Ctr, Seoul, South Korea. Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. Inst Gustave Roussy, Villejuif, France. Vrije Univ Amsterdam, Med Ctr, Dept Pulm Dis, Amsterdam, Netherlands. Seoul Natl Univ Hosp, Seoul 110744, South Korea. Novartis Pharma AG, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Vall dHebron Univ Hosp, Barcelona, Spain. NR 0 TC 5 Z9 5 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 7543 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804271 ER PT J AU Garrett, LA Growdon, WB Boruta, DM del Carmen, MG Priebe, AM Goodman, A Bradford, L Clark, RM Schorge, JO AF Garrett, Leslie A. Growdon, Whitfield Board Boruta, David M. del Carmen, Marcela G. Priebe, Anna M. Goodman, Annekathryn Bradford, Leslie Clark, Rachel Marie Schorge, John O. TI Primary debulking surgery (PDS) for stage IIIc ovarian cancer: Quo vadis? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 [Garrett, Leslie A.; Growdon, Whitfield Board; Boruta, David M.; del Carmen, Marcela G.; Priebe, Anna M.; Goodman, Annekathryn; Bradford, Leslie; Clark, Rachel Marie; Schorge, John O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e15568 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803597 ER PT J AU Gartrell, BA Hahn, NM Hutson, TE Sonpavde, G Hauke, RJ Starodub, A Small, AC Tsao, CK Galsky, MD AF Gartrell, Benjamin Adam Hahn, Noah M. Hutson, Thomas E. Sonpavde, Guru Hauke, Ralph J. Starodub, Alexander Small, Alexander C. Tsao, Che-Kai Galsky, Matt D. TI Phase II trial of gemcitabine and cisplatin plus ipilimumab as first-line treatment for metastatic urothelial carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Med Oncol, Dept Med, Houston, TX 77030 USA. Nebraska Canc Specialists, Omaha, NE USA. Goshen Ctr Canc Care, Goshen, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4676 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803064 ER PT J AU Gaughan, EM Cryer, SK Yeap, BY Jackman, DM Costa, DB AF Gaughan, Elizabeth Mary Cryer, Sarah K. Yeap, Beow Yong Jackman, David Michael Costa, Daniel Botelho TI Family history of lung cancer in never smokers with non-small cell lung cancer (NSCLC) and its association with tumors harboring epidermal growth factor receptor (EGFR) mutations. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 7579 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804222 ER PT J AU Geoerger, B Aerts, I Casanova, M Chisholm, JC Hargrave, DR Leary, S Ashley, DM Bouffet, E MacDonald, T Hurh, E Dey, J Kalambakas, S Amakye, DD Kieran, MW AF Geoerger, Birgit Aerts, Isabelle Casanova, Michela Chisholm, Julia C. Hargrave, Darren R. Leary, Sarah Ashley, David M. Bouffet, Eric MacDonald, Tobey Hurh, Eunju Dey, Jyotirmoy Kalambakas, Stacey Amakye, Dereck Dokyi Kieran, Mark W. TI A phase I/II study of LDE225, a smoothened (Smo) antagonist, in pediatric patients with recurrent medulloblastoma (MB) or other solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Inst Gustave Roussy, Villejuif, France. Inst Curie, Paris, France. Natl Canc Inst, I-20133 Milan, Italy. Royal Marsden Hosp, Sutton, Surrey, England. Seattle Childrens Hosp, Seattle, WA USA. Royal Childrens Hosp, Melbourne, Vic, Australia. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Emory Univ, Atlanta, GA 30322 USA. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharmaceut, Florham Pk, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 9519 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800268 ER PT J AU George, DJ Corn, PG Michaelson, MD Hammers, HJ Alumkal, JJ Ryan, CJ Bruce, JY Moran, S Lee, SY Mortimer, P Hussain, M AF George, Daniel J. Corn, Paul G. Michaelson, M. Dror Hammers, Hans J. Alumkal, Joshi J. Ryan, Charles J. Bruce, Justine Yang Moran, Susan Lee, Shih-Yuan Mortimer, Peter Hussain, Maha TI Safety and activity of the investigational agent orteronel (ortl) without prednisone in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) and rising prostate-specific antigen (PSA): Updated results of a phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Takeda Global Res & Dev Ctr Europe Ltd, London, England. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4549 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803344 ER PT J AU Gerstner, ER Zhang, Z Fink, JR Sorensen, GA L'Heureux, D Heckel, ML Dunning, B Muzi, M Mankoff, DA Barboriak, D AF Gerstner, Elizabeth Robins Zhang, Zheng Fink, James R. Sorensen, Gregory A. L'Heureux, Darryl Heckel, Martha L. Dunning, Bernadine Muzi, Mark Mankoff, David A. Barboriak, Daniel TI ACRIN 6684 assessment of tumor hypoxia in glioblastoma using 18F-fluoromisonidazole with PET and MRI. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Providence, RI 02912 USA. Univ Washington, Seattle, WA 98195 USA. Amer Coll Radiol, Philadelphia, PA USA. Amer Coll Radiol Imaging Network, Philadelphia, PA USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS10635 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801722 ER PT J AU Gerstner, ER Emblem, KE Chi, AS Eichler, AF Hochberg, F Drappatz, J Quant, EC Norden, AD Pinho, MC Polaskova, P Jennings, D Ancukiewicz, M Ivy, SP Wen, PY Jain, RK Sorensen, AG Batchelor, T AF Gerstner, Elizabeth Robins Emblem, Kyrre E. Chi, Andrew S. Eichler, April F. Hochberg, Fred Drappatz, Jan Quant, Eudocia Carmen Norden, Andrew David Pinho, Marco C. Polaskova, Pavlina Jennings, Dominique Ancukiewicz, Marek Ivy, S. Percy Wen, Patrick Y. Jain, Rakesh K. Sorensen, A. Gregory Batchelor, Tracy TI Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. AA Martinos Ctr Biomed Imaging, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hop, Martinos Ctr Biomed Imaging, Boston, MA USA. NCI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2009 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801527 ER PT J AU Gerstner, ER Emblem, KE Chi, AS Eichler, AF Hochberg, F Drappatz, J Quant, EC Norden, AD Pinho, MC Polaskova, P Jennings, D Ancukiewicz, M Ivy, SP Wen, PY Jain, RK Sorensen, AG Batchelor, T AF Gerstner, Elizabeth Robins Emblem, Kyrre E. Chi, Andrew S. Eichler, April F. Hochberg, Fred Drappatz, Jan Quant, Eudocia Carmen Norden, Andrew David Pinho, Marco C. Polaskova, Pavlina Jennings, Dominique Ancukiewicz, Marek Ivy, S. Percy Wen, Patrick Y. Jain, Rakesh K. Sorensen, A. Gregory Batchelor, Tracy TI Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. AA Martinos Ctr Biomed Imaging, Boston, MA USA. Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2009 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801525 ER PT J AU Ghobrial, IM Gertz, MA LaPlant, B Camoriano, JK Hayman, SR Lacy, M Chuma, S Harris, B Boswell, E Banwait, R Sheehy, P Ansell, SM DeAngelo, DJ Dispenzieri, A Bergsagel, L Reeder, CB Anderson, KC Richardson, PGG Treon, SP Witzig, TE AF Ghobrial, Irene M. Gertz, Morie A. LaPlant, Betsy Camoriano, John Kelly Hayman, Suzanne R. Lacy, Martha Chuma, Stacey Harris, Brianna Boswell, Erica Banwait, Ranjit Sheehy, Patricia Ansell, Stephen Maxted DeAngelo, Daniel J. Dispenzieri, Angela Bergsagel, Leif Reeder, Craig B. Anderson, Kenneth Carl Richardson, Paul Gerard Guy Treon, Steven P. Witzig, Thomas E. TI Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom macroglobulinemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Mayo Clin, Scottsdale, AZ USA. Mayo Clin, Coll Med, Scottsdale, AZ USA. Mayo Fdn, Scottsdale, AZ USA. Mayo Clin, Div Hematol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8043 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804009 ER PT J AU Gill, RR Heon, S Yeap, BY Butaney, M Lindeman, NI Rabin, MS Jackman, DM Janne, PA Johnson, BE AF Gill, Ritu R. Heon, Stephanie Yeap, Beow Yong Butaney, Mohit Lindeman, Neal Ian Rabin, Michael S. Jackman, David Michael Janne, Pasi Antero Johnson, Bruce E. CA Dana-Farber Canc Ctr TI Genomic profiling of non-small cell lung cancer (NSCLC) for personalized targeted therapy using CT-guided transthoracic needle biopsy (TTNB). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 10592 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803566 ER PT J AU Gnant, M Baselga, J Rugo, HS Noguchi, S Pritchard, KI Burris, HA Piccart-Gebhart, MJ Hart, LL Eakle, JF Mukai, H Iwata, H El-Hashimy, M Rao, S Taran, T Sahmoud, T Lebwohl, DE Hortobagyi, GN AF Gnant, Michael Baselga, Jose Rugo, Hope S. Noguchi, Shinzaburo Pritchard, Kathleen I. Burris, Howard A. Piccart-Gebhart, Martine J. Hart, Lowell L. Eakle, Janice F. Mukai, Hirofumi Iwata, Hiroji El-Hashimy, Mona Rao, Shantha Taran, Tanya Sahmoud, Tarek Lebwohl, David Edward Hortobagyi, Gabriel N. TI Effects of everolimus (EVE) on disease progression in bone and bone markers (BM) in patients (pts) with bone metastases (mets). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Med Univ Vienna, Dept Surg, Ctr Comprehens Canc, Vienna, Austria. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Osaka Univ, Osaka, Japan. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Sarah Cannon Res Inst, Nashville, TN USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Florida Canc Specialists, Ft Myers, FL USA. Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Novartis Pharmaceut, E Hanover, NJ USA. Novarits Pharmaceut, Florham Pk, NJ USA. Univ Texas Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 512 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800245 ER PT J AU Goldberg, SB Oxnard, GR Digumarthy, S Muzikansky, A Jackman, DM Lennes, IT Sequist, LV AF Goldberg, Sarah B. Oxnard, Geoffrey R. Digumarthy, Subba Muzikansky, Alona Jackman, David Michael Lennes, Inga Tolin Sequist, Lecia V. TI Chemotherapy with erlotinib or chemotherapy alone in advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors (TKI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7524 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804377 ER PT J AU Goldkorn, A Ely, B Quinn, DI Tangen, CM Tai, YC Twardowski, P Van Veldhuizen, PJ Agarwal, N Anthony, M Monk, CJP Garzotto, M Mack, PC Lara, P Higano, CS Hussain, M Vogelzang, NJ Cote, RJ Thompson, IM AF Goldkorn, Amir Ely, Benjamin Quinn, David I. Tangen, Catherine M. Tai, Yu-Chong Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Anthony, Michael Monk, Carducci J. P. Garzotto, Mark Mack, Philip C. Lara, Primo Higano, Celestia S. Hussain, Maha Vogelzang, Nicholas J. Cote, Richard J. Thompson, Ian Murchie CA Southwest Oncology Grp TI Results of telomerase activity measurements from live circulating tumor cells captured on a slot microfilter in a phase III SWOG-coordinated prostate cancer trial (S0421) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. SWOG Stat Ctr, Seattle, WA USA. CALTECH, Pasadena, CA 91125 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Kansas, Ctr Canc, Westwood, KS USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Portland VA Med Ctr, Portland, OR USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Washington, Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA 98195 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4663 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803108 ER PT J AU Gordon, MS Kluger, HM Shapiro, G Kurzrock, R Edelman, G Samuel, TA Moussa, AH Ramies, DA Laird, AD Schimmoller, F Shen, XD Daud, A AF Gordon, Michael S. Kluger, Harriet M. Shapiro, Geoffrey Kurzrock, Razelle Edelman, Gerald Samuel, Thomas A. Moussa, Ali H. Ramies, David A. Laird, A. Douglas Schimmoller, Frauke Shen, Xiaodong Daud, Adil TI Activity of cabozantinib (XL184) in metastatic melanoma: Results from a phase II randomized discontinuation trial (RDT) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Pinnacle Oncol Hematol, Scottsdale, AZ USA. Yale Canc Ctr, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Texas Oncol, Irving, TX USA. Georgia Hlth Sci Univ, Augusta, GA USA. Canc Care Associates, Tulsa, OK USA. Exelixis, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8531 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800567 ER PT J AU Goss, PE Barrios, CH Bell, R Finkelstein, DM Iwata, H Martin, M Braun, AH Ke, CL Maniar, T Coleman, RE AF Goss, Paul Edward Barrios, Carlos H. Bell, Richard Finkelstein, Dianne M. Iwata, Hiroji Martin, Miguel Braun, Ada H. Ke, Chunlei Maniar, Tapan Coleman, Robert Edward TI Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer who are at high risk of disease recurrence (D-CARE): An international, randomized, double-blind, placebo-controlled phase III clinical trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. PUCRS Sch Med, Porto Alegre, RS, Brazil. Barwon Hlth, Geelong, Vic, Australia. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Hosp Gen Gregorio Maranon, Madrid, Spain. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Sheffield, Sheffield, S Yorkshire, England. RI Barrios, Carlos/G-8525-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS670 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800240 ER PT J AU Govindan, R Hammerman, PS Hayes, DN Wilkerson, MD Baylin, S Meyerson, M AF Govindan, Ramaswamy Hammerman, Peter S. Hayes, David N. Wilkerson, Matthew D. Baylin, Stephen Meyerson, Matthew CA Canc Genome Atlas TCGA Grp TI Comprehensive genomic characterization of squamous cell carcinoma of the lung SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Univ N Carolina, Chapel Hill, NC USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 7006 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800025 ER PT J AU Greenup, RA Bardia, A Buckley, JM Niemierko, A Camp, M Coopey, S Gadd, M Schapira, L Taghian, AG Smith, BL Specht, MC AF Greenup, Rachel Adams Bardia, Aditya Buckley, Julliette M. Niemierko, Andrzej Camp, Melissa Coopey, Suzanne Gadd, Michele Schapira, Lidia Taghian, Alphonse G. Smith, Barbara L. Specht, Michelle Connolly TI Association of pathologic complete response following neoadjuvant chemotherapy with survival among young women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 1122 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800856 ER PT J AU Greer, JA McMahon, PM Tramontano, A Gallagher, ER Pirl, WF Jackson, VA Temel, JS AF Greer, Joseph A. McMahon, Pamela M. Tramontano, Angela Gallagher, Emily R. Pirl, William F. Jackson, Vicki A. Temel, Jennifer S. TI Effect of early palliative care on health care costs in patients with metastatic NSCLC. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 6004 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801235 ER PT J AU Gross, A Mann, S Kalfin, M Lane, S Weingart, S Bunnell, CA AF Gross, Anne Mann, Susan Kalfin, Michael Lane, Sharon Weingart, Saul Bunnell, Craig A. TI Performance teamwork training in ambulatory oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA e16559 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800570 ER PT J AU Haas, NB Manola, J Ky, B Flaherty, KT Uzzo, RG Wood, CG Kane, CJ Jewett, MAS Atkins, MB Dutcher, JP DiPaola, RS AF Haas, Naomi B. Manola, Judith Ky, Bonnie Flaherty, Keith T. Uzzo, Robert G. Wood, Christopher G. Kane, Christopher J. Jewett, Michael A. S. Atkins, Michael B. Dutcher, Janice P. DiPaola, Robert S. CA Eastern Cooperative Oncology Grp TI Cardiac safety analysis for a phase III trial of sunitinib (SU) or sorafenib (SO) or placebo (PLC) in patients (pts) with resected renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. Princess Margaret Hosp, Dept Urol, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. St Lukes Roosevelt Hosp, New York, NY USA. Canc Inst New Jersey, New Brunswick, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4500 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803239 ER PT J AU Haddad, RI Rabinowits, G Tishler, RB Adkins, D Khuri, FR Clark, J Lorch, JH Limaye, SA Wirth, LJ O'Neill, A Riley, S Posner, MR AF Haddad, Robert I. Rabinowits, Guilherme Tishler, Roy B. Adkins, Douglas Khuri, Fadlo Raja Clark, Joseph Lorch, Jochen H. Limaye, Sewanti Atul Wirth, Lori J. O'Neill, Anne Riley, Sarah Posner, Marshall R. TI The PARADIGM trial: A phase III study comparing sequential therapy (ST) to concurrent chemoradiotherapy (CRT) in locally advanced head and neck cancer (LANHC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai, New York, NY USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 5501 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803185 ER PT J AU Hahn, NM Daneshmand, S Posadas, EM Koch, MO Bihrle, R Foster, R Masterson, TA Cheng, L Liu, ZY Breen, T Fleming, MT Lance, R Ryan, CW Corless, CL Galsky, MD Alva, AS Mitchell, C Shen, SS Lerner, SP Sonpavde, G AF Hahn, Noah M. Daneshmand, Siamak Posadas, Edwin M. Koch, Michael O. Bihrle, Richard Foster, Richard Masterson, Timothy A. Cheng, Liang Liu, Ziyue Breen, Timothy Fleming, Mark T. Lance, Ray Ryan, Christopher W. Corless, Christopher L. Galsky, Matt D. Alva, Ajjai Shivaram Mitchell, Carmen Shen, Steven S. Lerner, Seth P. Sonpavde, Guru TI A phase II trial of neoadjuvant dasatinib (Neo-D) in muscle-invasive urothelial carcinoma of the bladder (miUCB): Hoosier Oncology Group GU07-122 trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Indiana Univ, Indianapolis, IN 46204 USA. Indiana Univ, Med Ctr, Dept Pathol & Lab Med, Indianapolis, IN USA. Indiana Univ, Div Biostat, Indianapolis, IN 46204 USA. Hoosier Oncol Grp, Indianapolis, IN USA. US Oncol Res, The Woodlands, TX USA. Virginia Oncol Associates, Hampton, VA USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR 97201 USA. Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Med Oncol, Houston, TX 77030 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4586 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802889 ER PT J AU Hale, J Olson, TA Nicholson, J Dang, H Krailo, MD Billmire, D Donachie, P Thornton, C Rodriguez-Galindo, C Frazier, AL AF Hale, Juliet Olson, Thomas Arthur Nicholson, James Dang, Ha Krailo, Mark D. Billmire, Deborah Donachie, Paul Thornton, Claire Rodriguez-Galindo, Carlos Frazier, A. Lindsay TI Carboplatin (CBP) versus cisplatin (CP) within prognostic groups in pediatric extracranial malignant germ cell tumors (MGCTs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Newcastle Upon Tyne Hosp Trust, Newcastle Upon Tyne, Tyne & Wear, England. Emory Univ, Atlanta, GA 30322 USA. Addenbrookes NHS Trust, Cambridge CB2 2QQ, England. Childrens Oncol Grp, Arcadia, CA USA. Riley Hosp Children, Indianapolis, IN USA. Childrens Canc & Leukaemia Grp, Leicester, Leics, England. Royal Hosp, Belfast, Antrim, North Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 9539 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800588 ER PT J AU Haluska, P Menefee, ME Plimack, ER Rosenberg, JE Northfelt, DW LaVallee, T Huang, WM Yu, XQ Viner, J LoRusso, P AF Haluska, Paul Menefee, Michael E. Plimack, Elizabeth R. Rosenberg, Jonathan E. Northfelt, Donald W. LaVallee, Theresa Huang, Wenmei Yu, Xiang-Qing Viner, Jaye LoRusso, Patricia TI Safety, pharmacokinetics, and antitumor activity of MEDI-573, an investigational monoclonal antibody that targets IGF-I and IGF-II, in adult patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mayo Clin, Rochester, MN USA. Mayo Clin, Jacksonville, FL 32224 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Mayo Clin, Scottsdale, AZ USA. MedImmune, Gaithersburg, MD USA. Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS2618 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802125 ER PT J AU Hamid, O Hwu, WJ Richards, JM Weber, JS Wolchok, JD Sznol, M Minor, DR Pavlick, AC Urba, WJ Hodi, FS Yang, A Michener, T Balogh, A McDermott, DF AF Hamid, Omid Hwu, Wen-Jen Richards, Jon M. Weber, Jeffrey S. Wolchok, Jedd D. Sznol, Mario Minor, David R. Pavlick, Anna C. Urba, Walter John Hodi, F. Stephen Yang, Arvin Michener, Tracy Balogh, Agnes McDermott, David F. TI Ipilimumab (Ipi) expanded access program (EAP) for patients (pts) with stage III/IV melanoma: 10 mg/kg cohort interim results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Angeles Clin & Res Inst, Santa Monica, CA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Oncol Specialists SC, Park Ridge, IL USA. Univ S Florida, H Lee Moffitt Canc Ctr, Comprehens Melanoma Res Ctr, Tampa, FL 33682 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Yale Canc Ctr, New Haven, CT USA. Calif Pacific Melanoma Ctr, San Francisco, CA USA. NYU, Inst Canc, New York, NY USA. Providence Portland Med Ctr, Portland, OR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. Bristol Myers Squibb Co, Braine Lalleud, Belgium. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8508 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800027 ER PT J AU Hanna, NH Dahlberg, SE Kolesar, J Hirsch, FR Ramalingam, SS Schiller, JH AF Hanna, Nasser H. Dahlberg, Suzanne Eleanor Kolesar, Jill Hirsch, Fred R. Ramalingam, Suresh S. Schiller, Joan H. TI Three-arm randomized phase II study of carboplatin (C) and paclitaxel (P) in combination with cetuximab (CET), IMC-A12, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology Group (ECOG) study (E4508) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Indiana Univ, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Univ Colorado, Ctr Canc, Aurora, CO USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 7516 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804330 ER PT J AU Hawryluk, EB O'Regan, KN Sheehy, N Guo, Y Dorosario, A Sakellis, C Jacene, HA Wang, LDC AF Hawryluk, Elena B. O'Regan, Kevin N. Sheehy, Niall Guo, Ye Dorosario, Andrew Sakellis, Chris Jacene, Heather A. Wang, Linda C. TI Positron emission tomography/computed tomography to improve staging and restaging in Merkel cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Cork Univ Hosp, Dept Radiol, Cork, Ireland. St James Hosp, Dublin, Ireland. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Ctr Cutaneous Oncol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mercy Med Ctr, Inst Canc Care, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8552 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800166 ER PT J AU Heist, RS Wang, XFF Hodgson, L Otterson, GA Stinchcombe, T Vokes, EE Socinski, MA AF Heist, Rebecca Suk Wang, Xiaofei F. Hodgson, Lydia Otterson, Gregory Alan Stinchcombe, Tom Vokes, Everett E. Socinski, Mark A. TI CALGB 30704: A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer (NSCLC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Canc & Leukemia Grp, Ctr Stat B, Durham, NC USA. Duke Univ, Durham, NC USA. Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Pittsburgh, Med Ctr, UPMC Canc Pavil, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7513 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804312 ER PT J AU Heng, DYC Choueiri, TK Lee, JL Harshman, LC Bjarnason, GA Knox, JJ MacKenzie, MJ Vaishampayan, UN Yuasa, T Tan, MH Rha, SY Donskov, F Agarwal, N Pal, SK Kollmannsberger, CK North, SA Rini, BI Wood, L AF Heng, Daniel Yick Chin Choueiri, Toni K. Lee, Jae-Lyun Harshman, Lauren Christine Bjarnason, Georg A. Knox, Jennifer J. MacKenzie, Mary J. Vaishampayan, Ulka N. Yuasa, Takeshi Tan, Min-Han Rha, Sun Young Donskov, Frede Agarwal, Neeraj Pal, Sumanta Kumar Kollmannsberger, Christian K. North, Scott A. Rini, Brian I. Wood, Lori TI An in-depth multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) that do not meet eligibility criteria for clinical trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA. Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. London Reg Canc Program, London, ON, Canada. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Canc Inst Hosp JFCR, Tokyo, Japan. Natl Canc Ctr, Singapore, Singapore. Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. City Hope Natl Med Ctr, Duarte, CA USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4536 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803080 ER PT J AU Heon, S Nishino, M Goldberg, SB Porter, J Sequist, LV Jackman, DM Johnson, BE AF Heon, Stephanie Nishino, Mizuki Goldberg, Sarah B. Porter, Jennifer Sequist, Lecia V. Jackman, David Michael Johnson, Bruce E. TI Response to EGFR tyrosine kinase inhibitor (TKI) retreatment after a drug-free interval in EGFR-mutant advanced non-small cell lung cancer (NSCLC) with acquired resistance. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 7525 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804267 ER PT J AU Hidalgo, M Calles, A Juric, D Dienstmann, R Perez, DR Messersmith, WA Blumenschein, GR Baselga, J Tabernero, J Cervantes-Ruiperez, A Jimeno, A Jin, D Bai, S Gurevich, P Nijem, I Holden, SN Davis, JD Halpern, W Pirzkall, A Xin, Y AF Hidalgo, Manuel Calles, Antonio Juric, Dejan Dienstmann, Rodrigo Perez, Desamparados Roda Messersmith, Wells A. Blumenschein, George R. Baselga, Jose Tabernero, Josep Cervantes-Ruiperez, Andres Jimeno, Antonio Jin, Denise Bai, Shuang Gurevich, Pavel Nijem, Ihsan Holden, Scott N. Davis, John D. Halpern, Wendy Pirzkall, Andrea Xin, Yan TI Human pharmacokinetic (PK) characterization of the novel dual-action anti-HER3/EGFR antibody MEHD7945A (MEHD) in patients with refractory/recurrent epithelial tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 START Madrid, Ctr Integral Oncol Clara Campal, Madrid, Spain. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Vall dHebron Univ Hosp, Mol Therapeut Res Unit, Barcelona, Spain. Hosp Clin, Dept Med Oncol, Colorectal Unit, Dept Surg, Valencia, Spain. Univ Colorado, Aurora, CO USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vall dHebron Univ Hosp, Barcelona, Spain. Univ Valencia, Dept Hematol & Med Oncol, INCLIVA, Valencia, Spain. Univ Colorado Denver, Div Med Oncol, Aurora, CO USA. Genentech Inc, San Francisco, CA 94080 USA. RI DAVIS, JOHN/I-7261-2012 OI DAVIS, JOHN/0000-0001-6282-1670 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 2567 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801620 ER PT J AU Hodi, FS Sznol, M McDermott, DF Carvajal, RD Lawrence, DP Topalian, SL Wigginton, J McDonald, D Kollia, G Gupta, AK Sosman, JA AF Hodi, F. Stephen Sznol, Mario McDermott, David F. Carvajal, Richard D. Lawrence, Donald P. Topalian, Suzanne Louise Wigginton, Jon McDonald, Dan Kollia, Georgia Gupta, Ashok Kumar Sosman, Jeffrey Alan TI Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced melanoma (MEL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Canc Ctr, New Haven, CT USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Bristol Myers Squibb Co, Princeton, NJ USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 8507 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802847 ER PT J AU Hong, NJL Hornicek, FJ Harmon, DC Choy, E Chen, YL Yoon, SS Nielsen, GP Szymonifka, J Yeap, BY DeLaney, TF Mullen, JT AF Hong, Nicole Jannelle Look Hornicek, Francis J. Harmon, David C. Choy, Edwin Chen, Yen-Lin Yoon, Sam S. Nielsen, G. Petur Szymonifka, Jackie Yeap, Beow Yong DeLaney, Thomas F. Mullen, John Thomas TI Neoadjuvant chemoradiotherapy for patients with high-risk extremity and truncal sarcomas: A 10-year follow-up study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 [Hong, Nicole Jannelle Look; Hornicek, Francis J.; Harmon, David C.; Choy, Edwin; Chen, Yen-Lin; Yoon, Sam S.; Nielsen, G. Petur; Szymonifka, Jackie; Yeap, Beow Yong; DeLaney, Thomas F.; Mullen, John Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 10058 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801385 ER PT J AU Hong, TS Ryan, DP Borger, DR Blaszkowsky, LS Yeap, BY Deshpande, V Wo, JYL Wadlow, RC Kwak, EL Allen, JN Clark, JW Zhu, AX Ferrone, C Mamon, HJ Adams, JA Winrich, B Grillo, T DeLaney, TF Fernandez-del Castillo, C AF Hong, Theodore S. Ryan, David P. Borger, Darrell R. Blaszkowsky, Lawrence Scott Yeap, Beow Yong Deshpande, Vikram Wo, Jennifer Yon-Li Wadlow, Raymond Couric Kwak, Eunice Lee Allen, Jill N. Clark, Jeffrey W. Zhu, Andrew X. Ferrone, Cristina Mamon, Harvey J. Adams, Judith A. Winrich, Barbara Grillo, Tarin DeLaney, Thomas F. Fernandez-del Castillo, Carlos TI Phase I/II study of preoperative (pre-op) short course chemoradiation (CRT) with proton beam therapy (PBT) and capecitabine (cape) followed by early surgery for resectable pancreatic ductal adenocarcinoma (PDAC) of the head SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4021 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804685 ER PT J AU Hunter, ZR Xu, L Yang, G Zhou, YS Liu, X Cao, Y Tripsas, C Manning, RJ Patterson, CJ Sheehy, PS Treon, SP AF Hunter, Zachary R. Xu, Lian Yang, Guang Zhou, Yangsheng Liu, Xia Cao, Yang Tripsas, Christina Manning, Robert J. Patterson, Christopher J. Sheehy, Patricia S. Treon, Steven P. TI Use of whole genome sequencing to identify highly recurrent somatic mutations in Waldenstrom's macroglobulinemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 [Hunter, Zachary R.; Xu, Lian; Yang, Guang; Zhou, Yangsheng; Liu, Xia; Cao, Yang; Tripsas, Christina; Manning, Robert J.; Patterson, Christopher J.; Sheehy, Patricia S.; Treon, Steven P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 8107 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803727 ER PT J AU Hutson, TE Dang, LH Lauer, RC Starodub, A Hauke, RJ Galsky, MD Bylow, KA Logan, T Cowey, CL Bibby, DC Kremmidiotis, G Doolin, EE Lavranos, TC Sonpavde, G Hahn, NM Sweeney, C Sarantopoulos, J AF Hutson, Thomas E. Dang, Long H. Lauer, Richard C. Starodub, Alexander Hauke, Ralph J. Galsky, Matt D. Bylow, Kathryn A. Logan, Theodore Cowey, Charles Lance Bibby, David C. Kremmidiotis, Gabriel Doolin, Elizabeth E. Lavranos, Tina C. Sonpavde, Guru Hahn, Noah M. Sweeney, Christopher Sarantopoulos, John CA Hoosier Oncol Grp TI Phase I results of a phase I/II trial of BNC105P with everolimus in metastatic renal cell carcinoma (mRCC) patients previously treated with VEGFR tyrosine kinase inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 US Oncol Res LLC, McKesson Specialty Hlth, The Woodlands, TX USA. Baylor Sammons Canc Ctr, Texas Oncol PA, Dallas, TX USA. Univ Florida, Gainesville, FL USA. Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. Goshen Ctr Canc Care, Goshen, IN USA. Nebraska Canc Specialists, Omaha, NE USA. Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Baylor Sammons Canc Ctr, Dallas, TX USA. Bionomics Ltd, Thebarton, Australia. Texas Oncol, Houston, TX USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Med Oncol, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA 4603 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802786 ER PT J AU Hutson, TE Rathmell, K Hudes, GR Kabbinavar, F Vogelzang, NJ Knox, JJ Cowey, CL Cho, DC Choueiri, TK AF Hutson, Thomas E. Rathmell, Kimryn Hudes, Gary R. Kabbinavar, Fairooz Vogelzang, Nicholas J. Knox, Jennifer J. Cowey, C. Lance Cho, Daniel C. Choueiri, Toni K. TI A phase II biomarker assessment of tivozanib in oncology (BATON) trial in patients (pts) with advanced renal cell carcinoma (RCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Texas Oncol Baylor A Charles Sammons Canc Ctr, Dallas, TX USA. Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Calif Los Angeles, Inst Urol Oncol, Los Angeles, CA USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. US Oncol Res, Las Vegas, NV USA. Univ Hlth Network, Toronto, ON, Canada. US Oncol Res, Dallas, TX USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS4686 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802664 ER PT J AU Iasonos, A Keung, E Zivanovic, O Mancari, R Peiretti, M Nucci, M George, S Colombo, N Carinelli, S Hensley, ML Raut, CP AF Iasonos, Alexia Keung, Emily Zivanovic, Oliver Mancari, Rosanna Peiretti, Michele Nucci, Marisa George, Suzanne Colombo, Nicoletta Carinelli, Silvestro Hensley, Martee Leigh Raut, Chandrajit P. TI External validation of a nomogram predicting overall survival (OS) of women with uterine leiomyosarcoma (ULMS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Univ Hosp Bonn, Bonn, Germany. European Inst Oncol, Milan, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Milano Bicocca, Milan, Italy. Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 5090 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009803583 ER PT J AU Infante, JR Gandhi, L Shapiro, G Burris, HA Bendell, JC Baselga, J Hsu, K Faivre, T Asatiani, E Heist, RS AF Infante, Jeffrey R. Gandhi, Leena Shapiro, Geoffrey Burris, Howard A. Bendell, Johanna C. Baselga, Jose Hsu, Karl Faivre, Thea Asatiani, Ekatherine Heist, Rebecca Suk TI Phase lb combination trial of a MEK inhibitor, pimasertib (MSC1936369B), and a PI3K/mTOR inhibitor, SAR245409, in patients with locally advanced or metastatic solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sanofi, Cambridge, MA USA. Merck Serono SA, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS3118 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009802382 ER PT J AU Irwin, M Gottlieb, L Cartmel, B Ercolano, E Rothbard, M Zhou, Y Schwartz, PE Ligibel, JA Von Gruenigen, VE Risch, H AF Irwin, Melinda Gottlieb, Linda Cartmel, Brenda Ercolano, Elizabeth Rothbard, Marianna Zhou, Yang Schwartz, Peter E. Ligibel, Jennifer A. Von Gruenigen, Vivian E. Risch, Harvey TI Trial of exercise in ovarian cancer survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Yale Univ, New Haven, CT USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Summa Akron City Hosp, Akron, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS1614 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009801175 ER PT J AU Irwin, M Cartmel, B Ercolano, E Fiellin, M Rothbard, M Capozza, S Zhou, Y Schmitz, K Ligibel, JA Hershman, DL Neogi, T Gross, CP AF Irwin, Melinda Cartmel, Brenda Ercolano, Elizabeth Fiellin, Martha Rothbard, Marianna Capozza, Scott Zhou, Yang Schmitz, Kathryn Ligibel, Jennifer A. Hershman, Dawn L. Neogi, Tuhina Gross, Cary P. TI Aromatase inhibitors, arthralgias, and exercise in breast cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Yale Univ, New Haven, CT USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Med Ctr, New York, NY USA. Boston Univ, Boston, MA 02215 USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 7 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA TPS669 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800322 ER PT J AU Janne, PA Shaw, AT Pereira, JR Jeannin, G Vansteenkiste, J Barrios, CH Franke, FA Grinsted, L Smith, PD Zazulina, V Smith, IC Crino, L AF Janne, Pasi A. Shaw, Alice Tsang Pereira, Jose Rodrigues Jeannin, Gaelle Vansteenkiste, Johan Barrios, Carlos H. Franke, Fabio A. Grinsted, Lynda Smith, Paul D. Zazulina, Victoria Smith, Ian C. Crino, Lucio TI Phase II double-blind, randomized study of selumetinib (SEL) plus docetaxel (DOC) versus DOC plus placebo as second-line treatment for advanced KRAS mutant non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Inst Brasileiro Cancerol Torac, Sao Paulo, Brazil. Serv Pneumol Oncol Thorac, Clermont Ferrand, France. Univ Hosp Gasthuisberg, Resp Oncol Unit, B-3000 Louvain, Belgium. PUCRS Sch Med, Porto Alegre, RS, Brazil. Hosp Caridade Ijui, Ijui, Brazil. AstraZeneca, Macclesfield, Cheshire, England. Univ Perugia, I-06100 Perugia, Italy. RI Vansteenkiste, Johan/B-8191-2014; Barrios, Carlos/G-8525-2015 OI Vansteenkiste, Johan/0000-0002-6721-2775; NR 0 TC 11 Z9 12 U1 1 U2 6 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA 7503 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009804172 ER PT J AU Jeon, JY Jeong, DH Park, MK Ligibel, JA Meyerhardt, JA Kim, NK AF Jeon, Justin Y. Jeong, Deok Hyun Park, Min Keun Ligibel, Jennifer A. Meyerhardt, Jeffrey A. Kim, Nam Kyu TI Impact of diabetes on site-specific oncologic outcome in stage I-III colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract 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) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Yonsei Univ Coll Med, Dept Surg, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY 20 PY 2012 VL 30 IS 15 SU S MA e14114 PG 1 WC Oncology SC Oncology GA 131QQ UT WOS:000318009800827 ER EF