FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pierce, C Ozzello, D Keniston, A Stickrath, C Health, D AF Pierce, Cason Ozzello, Daniel Keniston, Angela Stickrath, Chad Health, Denver TI THE FREQUENCY OF ATTENDING-LED DISCUSSION OF TEST ORDERING PRINCIPLES DURING INTERNAL MEDICINE WARDS ROUNDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Pierce, Cason] Denver Hlth, Denver, CO USA. [Keniston, Angela] Denver Hlth & Hosp Author, Denver, CO USA. [Stickrath, Chad] Denver VA Med Ctr, Denver, CO USA. [Pierce, Cason; Ozzello, Daniel] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197468 BP S272 EP S273 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901121 ER PT J AU Primack, BA Shensa, A Sidani, J Colditz, J Brook, J Fine, MJ AF Primack, Brian A. Shensa, Ariel Sidani, Jaime Colditz, Jason Brook, Judith Fine, Michael J. TI WATERPIPE TOBACCO SMOKING AMONG US YOUNG ADULTS BOTH IN AND NOT IN SCHOOL: A NATIONALLY-REPRESENTATIVE STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Primack, Brian A.; Shensa, Ariel; Sidani, Jaime; Colditz, Jason] Univ Pittsburgh, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Brook, Judith] NYU, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197948 BP S299 EP S300 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901179 ER PT J AU Primack, BA Carroll, M Weiss, PM Shihadeh, A Shensa, A Farley, S Fine, MJ Eissenberg, T Nayak, S AF Primack, Brian A. Carroll, Mary Weiss, Patricia M. Shihadeh, Alan Shensa, Ariel Farley, Steven Fine, Michael J. Eissenberg, Thomas Nayak, Smita TI SYSTEMATIC REVIEW AND META-ANALYSIS OF INHALED TOXICANTS FROM WATERPIPE AND CIGARETTE SMOKING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Primack, Brian A.; Weiss, Patricia M.; Shensa, Ariel; Farley, Steven] Univ Pittsburgh, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Carroll, Mary] Squirrel Hill Hlth Ctr, Pittsburgh, PA USA. [Shihadeh, Alan] Amer Univ Beirut, Beirut, Lebanon. [Nayak, Smita] Swedish Ctr Res & Innovat, Seattle, WA USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198875 BP S262 EP S262 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901098 ER PT J AU Primack, BA Soneji, S Stoolmiller, M Fine, MJ Sargent, J AF Primack, Brian A. Soneji, Samir Stoolmiller, Michael Fine, Michael J. Sargent, Jim TI INITIATION OF CIGARETTE SMOKING AFTER ELECTRONIC CIGARETTE USE: A NATIONAL STUDY OF YOUNG ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Primack, Brian A.] Univ Pittsburgh, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Soneji, Samir; Sargent, Jim] Dartmouth Coll, Sch Med, Hanover, NH USA. [Stoolmiller, Michael] Oregon Social Learning Ctr, Eugene, OR 97401 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198326 BP S193 EP S193 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900331 ER PT J AU Quinn, MA Li, LL Prigerson, HG Simon, SR AF Quinn, Mariah A. Li, Lingling Prigerson, Holly G. Simon, Steven R. TI A LONGITUDINAL ASSESSMENT OF DEPRESSIVE SYMPTOMS DURING INTERNAL MEDICINE RESIDENCY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Quinn, Mariah A.] Univ Wisconsin, Middleton, WI USA. [Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY USA. [Li, Lingling] Harvard Pilgrim HealthCare Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196024 BP S85 EP S85 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900092 ER PT J AU Quinones, A Joos, S Hart, KD Rosales, A Perrin, N Kansagara, D AF Quinones, Ana Joos, Sandra Hart, Kyle D. Rosales, Ana Perrin, Nancy Kansagara, Devan TI THE EFFECTS OF IMPLEMENTING A PATIENT-CENTERED MEDICAL HOME MODEL ON EMERGENCY UTILIZATION IN A VA HEALTH CARE SETTING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Quinones, Ana; Hart, Kyle D.; Kansagara, Devan] OHSU, Portland, OR USA. [Joos, Sandra] Portland VA Med Ctr, Portland, OR USA. [Kansagara, Devan] VA Portland Hlth Care Syst, Portland, OR USA. [Rosales, Ana; Perrin, Nancy] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2201320 BP S271 EP S272 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901119 ER PT J AU Radomski, TR Zhao, XH Thorpe, CT Good, C Mor, M Fine, MJ Gellad, WF AF Radomski, Thomas R. Zhao, Xinhua Thorpe, Carolyn T. Good, Chester Mor, Maria Fine, Michael J. Gellad, Walid F. TI TYPOLOGIES OF VA AND MEDICARE UTILIZATION AMONG DUALLY ENROLLED VETERANS WITH TYPE 2 DIABETES: A LATENT CLASS ANALYSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Thorpe, Carolyn T.; Mor, Maria] Univ Pittsburgh, Pittsburgh, PA USA. [Radomski, Thomas R.; Zhao, Xinhua; Thorpe, Carolyn T.; Good, Chester; Mor, Maria; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, VA Pittsburgh, Pittsburgh, PA USA. [Radomski, Thomas R.; Good, Chester; Fine, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196785 BP S290 EP S291 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901159 ER PT J AU Raghavan, S Pachucki, MC Chang, YC Dupuis, J Meigs, JB AF Raghavan, Sridharan Pachucki, Mark C. Chang, Yuchiao Dupuis, Josee Meigs, James B. TI FAMILIAL CLUSTERING OF DIABETES INFLUENCES TYPE 2 DIABETES RISK MORE STRONGLY THAN SOCIAL CLUSTERING OF OBESITY: A SOCIAL NETWORK ANALYSIS IN THE FRAMINGHAM OFFSPRING STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Dupuis, Josee] Boston Univ SPH, Boston, MA USA. [Chang, Yuchiao] Harvard Univ, Sch Med, Boston, MA USA. [Raghavan, Sridharan; Pachucki, Mark C.; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199071 BP S162 EP S162 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900263 ER PT J AU Ramsey, AL Otazo, M Caruso, A Bates, JT AF Ramsey, Allison L. Otazo, Maria Caruso, Andrew Bates, Jeffrey T. TI PRIMARILY SUSPECT CHOLANGIOCARCINOMA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Ramsey, Allison L.; Otazo, Maria; Caruso, Andrew] Baylor Coll Med, Houston, TX 77030 USA. [Bates, Jeffrey T.] VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2200185 BP S439 EP S440 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901547 ER PT J AU Ray, L Zingmond, D Vangala, S Sayles, JN Tu, M Chu, LH Pollack, BA Malloy, D Saliba, D AF Ray, Lhasa Zingmond, David Vangala, Sitaram Sayles, Jennifer N. Tu, Michael Chu, Li-Hao Pollack, Bruce A. Malloy, Demetria Saliba, Debra TI AN EVALUATION OF THE IMPACT OF CALIFORNIA'S TRANSITION TO MANAGED CARE ON HEALTH CARE UTILIZATION BY MEDICAID SENIORS AND PERSONS WITH DISABILITIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Zingmond, David] Univ Calif Los Angeles, Los Angeles, CA USA. [Saliba, Debra] Univ Calif Los Angeles, Borun Ctr, VA GRECC, RAND, Los Angeles, CA USA. [Ray, Lhasa; Vangala, Sitaram] Univ Calif Los Angeles, Culver City, CA USA. [Ray, Lhasa; Zingmond, David; Saliba, Debra] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Sayles, Jennifer N.] Los Angeles Cty, Los Angeles, CA USA. [Tu, Michael; Chu, Li-Hao; Pollack, Bruce A.; Malloy, Demetria] LA Care Hlth Plan, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2193338 BP S99 EP S100 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900128 ER PT J AU Reddy, S Rose, D Burgess, J Charns, M Yano, EM AF Reddy, Shivani Rose, Danielle Burgess, James Charns, Martin Yano, Elizabeth M. TI THE ROLE OF ORGANIZATIONAL FACTORS IN THE PROVISION OF COMPREHENSIVE WOMEN'S HEALTHCARE IN THE VETERANS HEALTH ADMINISTRATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Reddy, Shivani] Boston Univ, Boston, MA 02215 USA. [Rose, Danielle; Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr, Sepulveda, CA USA. [Reddy, Shivani] VA Boston Healthcare, Boston, MA USA. [Burgess, James; Charns, Martin] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197702 BP S280 EP S280 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901138 ER PT J AU Rhodes, C Percac-Lima, S AF Rhodes, Corinne Percac-Lima, Sanja TI DEVELOPMENT OF OBESITY AND RELATED DISEASES IN A PROSPECTIVE LONGITUDINAL COHORT OF AFRICAN REFUGEES COMPARED TO MATCHED REGIONAL CONTROLS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rhodes, Corinne; Percac-Lima, Sanja] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2190044 BP S138 EP S138 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900211 ER PT J AU Rosland, AM Wong, E Zulman, DM Piegari, RI Prenovost, K Fihn, SD Nelson, KM AF Rosland, Ann-Marie Wong, Edwin Zulman, Donna M. Piegari, Rebecca I. Prenovost, Katherine Fihn, Stephan D. Nelson, Karin M. TI HIGHER LEVEL OF PATIENT-CENTERED MEDICAL HOME IMPLEMENTATION ASSOCIATED WITH IMPROVEMENTS IN CLINICAL QUALITY OF CARE IN THE NATION-WIDE VHA PACT INITIATIVE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Wong, Edwin; Nelson, Karin M.] Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Nelson, Karin M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Rosland, Ann-Marie; Prenovost, Katherine] VA Ann Arbor, Ann Arbor, MI USA. [Piegari, Rebecca I.; Fihn, Stephan D.] Dept Vet Affairs, Seattle, WA USA. [Rosland, Ann-Marie] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Zulman, Donna M.] VA Palo Alto, Palo Alto, CA USA. [Zulman, Donna M.] Stanford Univ, Palo Alto, CA 94304 USA. RI Rosland, Annmarie/B-7750-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198149 BP S175 EP S176 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900292 ER PT J AU Ryskina, KL Holmboe, E Bernabeo, EC Kim, EJ Shea, JA Long, J AF Ryskina, Kira L. Holmboe, Eric Bernabeo, Elizabeth C. Kim, Esther J. Shea, Judy A. Long, Judith TI PHYSICIAN AWARENESS AND USE OF OVERTREATMENT GUIDELINES IN PRACTICE: A NATIONAL SURVEY OF US INTERNISTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Holmboe, Eric] ACGME, Philadelphia, PA USA. [Bernabeo, Elizabeth C.] Amer Board Internal Med, Philadelphia, PA USA. [Long, Judith] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ryskina, Kira L.; Kim, Esther J.; Shea, Judy A.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199369 BP S228 EP S228 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901022 ER PT J AU Silverman, JB Nelson, KM Krieger, J AF Silverman, Julie B. Nelson, Karin M. Krieger, James TI INCORPORATING COMMUNITY HEALTH WORKERS INTO THE VA: WHAT DO VETERANS THINK? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Nelson, Karin M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Silverman, Julie B.] VA Puget Sound, Seattle, WA USA. [Krieger, James] Publ Hlth Seattle King Cty, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2191031 BP S191 EP S191 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900326 ER PT J AU Silverman, JB Krieger, J Nelson, KM AF Silverman, Julie B. Krieger, Jim Nelson, Karin M. TI A LOOK INSIDE COMMUNITY HEALTH WORKERS' VISITS: A QUALITATIVE STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Nelson, Karin M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Silverman, Julie B.] VA Puget Sound, Seattle, WA USA. [Krieger, Jim] Act Hlth Food, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198635 BP S85 EP S86 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900093 ER PT J AU Simmons, LH Hewitt, S Leavitt, L Sepucha, KR AF Simmons, Leigh H. Hewitt, Sarah Leavitt, Lauren Sepucha, Karen R. TI EVALUATION OF A PATIENT DECISION AID FOR ACUTE LOW BACK PAIN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Simmons, Leigh H.; Hewitt, Sarah; Leavitt, Lauren; Sepucha, Karen R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2200232 BP S152 EP S153 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900242 ER PT J AU Simonetti, JA Sylling, PW Nelson, KM Joos, S Mohr, D Curtis, I Taylor, L Harvey, CB Schectman, G Fihn, SD Helfrich, CD AF Simonetti, Joseph A. Sylling, Philip W. Nelson, Karin M. Joos, Sandra Mohr, David Curtis, Idamay Taylor, Leslie Harvey, Chip B. Schectman, Gordon Fihn, Stephan D. Helfrich, Christian D. TI PATIENT-CENTERED MEDICAL HOME IMPLEMENTATION AND BURNOUT AMONG VA PRIMARY CARE EMPLOYEES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Joos, Sandra] Portland VA Med Ctr, Portland, OR USA. [Nelson, Karin M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Simonetti, Joseph A.; Taylor, Leslie] VA, Seattle, WA USA. [Mohr, David] VA Boston Healthcare Syst, Boston, MA USA. [Helfrich, Christian D.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Schectman, Gordon] Vet Affairs Cent Off, Milwaukee, WI USA. [Sylling, Philip W.; Curtis, Idamay; Harvey, Chip B.; Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198324 BP S223 EP S223 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901010 ER PT J AU Singh, JM Pian, J Mi, XL Quaraglia, BA Cloutier, MO Krakower, T AF Singh, Jolene M. Pian, Julia Mi, Xiaoli Quaraglia, Barbara A. Cloutier, Meaghan O. Krakower, ThaliaM. TI BRIDGE-TO-CARE: IMPLEMENTING A QUALITY IMPROVEMENT INITIATIVE TO TRANSITION PATIENTS TO A PERMANENT PRIMARY CARE PROVIDER (PCP) THROUGH INTERPROFESSIONAL COLLABORATION IN THE CRIMSON CARE COLLABORATIVE-INTERNAL MEDICINE ASSOCIATES (CCC-IMA) CLINIC (2012-2015) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Singh, Jolene M.; Pian, Julia; Mi, Xiaoli; Quaraglia, Barbara A.; Cloutier, Meaghan O.; Krakower, ThaliaM.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2200904 BP S524 EP S525 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902191 ER PT J AU Song, ZR Wallace, J Neprash, H McKellar, M Chernew, ME McWilliams, JM AF Song, Zirui Wallace, Jacob Neprash, Hannah McKellar, Michael Chernew, Michael E. McWilliams, J. Michael TI MEDICARE FEE CUTS AND PHYSICIAN-HOSPITAL INTEGRATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Song, Zirui; McKellar, Michael; Chernew, Michael E.; McWilliams, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Song, Zirui] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wallace, Jacob; Neprash, Hannah] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2193920 BP S208 EP S209 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900365 ER PT J AU Spataro, B Tulsky, A Comer, D Rubio, D Spagnoletti, C AF Spataro, Brielle Tulsky, Asher Comer, Diane Rubio, Doris Spagnoletti, Carla TI BRIDGING THE GAP: A POST HOSPITAL DISCHARGE VISIT CURRICULUM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Spataro, Brielle] UPMC Presbyterian Hosp, Pittsburgh, PA USA. [Tulsky, Asher; Comer, Diane; Rubio, Doris; Spagnoletti, Carla] Univ Pittsburgh, Pittsburgh, PA USA. [Spataro, Brielle] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2193329 BP S488 EP S489 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902109 ER PT J AU Stahl, J Denninger, JW Mehta, DH Goldman, R Benson, H AF Stahl, James Denninger, John W. Mehta, Darshan H. Goldman, Roberta Benson, Herbert TI RELAXATION RESPONSE AND RESILIENCY TRAINING AND ITS EFFECT ON RESOURCE UTILIZATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Stahl, James; Denninger, John W.; Mehta, Darshan H.; Goldman, Roberta; Benson, Herbert] Massachusetts Gen Hosp, Swampscott, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2195783 BP S246 EP S246 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901066 ER PT J AU Sue, K Dickman, SL Kandola, M Choi, S Abo-Sido, N Jones, MM Moss, J Cohen, MJ AF Sue, Kimberly Dickman, Samuel L. Kandola, Manjinder Choi, Stephanie Abo-Sido, Nora Jones, Meissa M. Moss, Jacquelyn Cohen, Marya J. TI DELIVERING PRIMARY CARE BEHIND BARS: DEVELOPING A STUDENT-FACULTY COLLABORATIVE CLINIC IN A BOSTON JAIL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Moss, Jacquelyn] Harvard Univ, Sch Med, MGH Chelsea, Boston, MA USA. [Cohen, Marya J.] MGH, Boston, MA USA. [Jones, Meissa M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sue, Kimberly; Dickman, Samuel L.; Kandola, Manjinder; Choi, Stephanie; Abo-Sido, Nora] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2191972 BP S490 EP S490 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902113 ER PT J AU Tobey, M Bui, AH Peters, AS Chien, AT AF Tobey, Matthew Bui, Anthony H. Peters, Antoinette S. Chien, Alyna T. TI THE IMPACT OF PRIMARY CARE REDESIGN ON RESIDENTS' EXPERIENCE IN CONTINUITY CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Chien, Alyna T.] Harvard Univ, Sch Med, Boston, MA USA. [Peters, Antoinette S.] Harvard Univ, Sch Med, Brookline, MA USA. [Tobey, Matthew] Massachusetts Gen Hosp, Somerville, MA USA. [Bui, Anthony H.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2197828 BP S276 EP S276 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901128 ER PT J AU Vassy, JL Ho, YL Gagnon, DR Gaziano, JM Honerlaw, J Raju, S Wilson, PW Cho, K AF Vassy, Jason L. Ho, Yuk-Lam Gagnon, David R. Gaziano, J. M. Honerlaw, Jacqueline Raju, Sanjay Wilson, Peter W. Cho, Kelly TI EFFECT OF BASELINE TIMEFRAME ON POTENTIAL BIAS IN RISK FACTOR ASSESSMENT IN AN EHR-BASED COHORT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Vassy, Jason L.; Ho, Yuk-Lam; Gagnon, David R.; Gaziano, J. M.; Honerlaw, Jacqueline; Raju, Sanjay; Cho, Kelly] VA Boston Healthcare Syst, Boston, MA USA. [Wilson, Peter W.] Atlanta VA Med Ctr, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2181953 BP S147 EP S148 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900231 ER PT J AU Vassy, JL Christensen, KD Robinson, JO Murray, MF McGuire, AL Green, RC AF Vassy, Jason L. Christensen, Kurt D. Robinson, Jill Oliver Murray, Michael F. McGuire, Amy L. Green, Robert C. TI CLINICAL DECISION-MAKING AROUND THE GENOME SEQUENCING RESULTS OF HEALTHY ADULTS: PRELIMINARY RESULTS FROM THE MEDSEQ PROJECT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Robinson, Jill Oliver; McGuire, Amy L.] Baylor Coll Med, Houston, TX 77030 USA. [Vassy, Jason L.; Christensen, Kurt D.; Green, Robert C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Vassy, Jason L.; Christensen, Kurt D.; Green, Robert C.] Harvard Univ, Sch Med, Boston, MA USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Boston, MA USA. [Murray, Michael F.] Geisinger Hlth Syst, Danville, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2184434 BP S120 EP S121 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900172 ER PT J AU Vimalananda, V Dvorin, K Berlowitz, D Fincke, G Meterko, M Bokhour, BG AF Vimalananda, Varsha Dvorin, Kelly Berlowitz, Dan Fincke, Graeme Meterko, Mark Bokhour, Barbara G. TI WHAT IS SPECIALTY CARE COORDINATION? PERSPECTIVES OF THE "TRIAD"-PATIENT, PCP AND SPECIALIST SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Vimalananda, Varsha; Dvorin, Kelly; Berlowitz, Dan; Fincke, Graeme; Bokhour, Barbara G.] ENRM Vet Affairs Med Ctr, Bedford, MA USA. [Meterko, Mark] VA Boston Healthcare Syst, Boston, MA USA. [Vimalananda, Varsha] Boston Univ, Sch Med, Boston, MA 02118 USA. [Berlowitz, Dan; Fincke, Graeme; Meterko, Mark; Bokhour, Barbara G.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2195820 BP S302 EP S303 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901185 ER PT J AU Wachterman, MW Pilver, C Smith, D Lipsitz, SR Ersek, M Keating, NL AF Wachterman, Melissa W. Pilver, Corey Smith, Dawn Lipsitz, Stuart R. Ersek, Mary Keating, Nancy L. TI QUALITY OF END-OF-LIFE CARE PROVIDED TO PATIENTS WITH DIFFERENT LIFE-LIMITING CONDITIONS IN THE VETERANS HEALTH ADMINISTRATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Wachterman, Melissa W.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Pilver, Corey] VA Boston Healthcare Syst, Boston, MA USA. [Smith, Dawn; Ersek, Mary] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Lipsitz, Stuart R.; Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2191203 BP S238 EP S238 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901048 ER PT J AU Walling, A Ahluwalia, S Wenger, N Smith, P Booth, M Roth, C Lorenz, K Kanwal, F Dy, SM Asch, S AF Walling, Anne Ahluwalia, Sangeeta Wenger, Neil Smith, Patty Booth, Marika Roth, Carol Lorenz, Karl Kanwal, Fasiha Dy, Sydney M. Asch, Steven TI PALLIATIVE CARE QUALITY INDICATORS FOR PATIENTS WITH END STAGE LIVER DISEASE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Dy, Sydney M.] Johns HOpkins, Baltimore, MD USA. [Ahluwalia, Sangeeta; Smith, Patty; Booth, Marika; Roth, Carol] RAND Corp, Encino, CA USA. [Wenger, Neil] Univ Calif Los Angeles, Los Angeles, CA USA. [Walling, Anne] Univ Calif Los Angeles, Studio City, CA USA. [Asch, Steven] VA, Menlo Pk, CA USA. [Lorenz, Karl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kanwal, Fasiha] Houston VA, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196734 BP S219 EP S219 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900387 ER PT J AU Warde, C Ching, WT Sohmer, R AF Warde, Carole Ching, Wendell T. Sohmer, Robin TI ENHANCING RESILIENCE TO PROMOTE VA PATIENT-CENTERED MEDICAL HOME TRANSFORMATION AND THE UNTOWARD EFFECTS OF THE NATIONAL ACCESS CRISIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Warde, Carole] Greater Los Angeles VA Hlth Syst, North Hills, CA USA. [Ching, Wendell T.; Sohmer, Robin] VA Sepulveda Amb Care Ctr, North Hills, CA USA. [Warde, Carole; Ching, Wendell T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2194553 BP S516 EP S516 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386902173 ER PT J AU Washington, DL Hamilton, AB Cordasco, KM AF Washington, Donna L. Hamilton, Alison B. Cordasco, Kristina M. TI VULNERABILITY FOR HEALTHCARE COMMUNICATION GAPS FOR USERS OF VA PURCHASED CARE: IMPLICATIONS FOR THE VETERANS CHOICE ACT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Washington, Donna L.; Hamilton, Alison B.; Cordasco, Kristina M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Washington, Donna L.; Hamilton, Alison B.; Cordasco, Kristina M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2198688 BP S80 EP S80 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900079 ER PT J AU Young, EA Stickrath, C Calderon, A Chapman, E Gonzalo, J Kuperman, E Lopez, M Smith, CJ Sweigart, JR Theobald, C Burke, RE AF Young, Eric A. Stickrath, Chad Calderon, Aaron Chapman, Elizabeth Gonzalo, Jed Kuperman, Ethan Lopez, Max Smith, Christopher J. Sweigart, Joseph R. Theobald, Cecilia Burke, Robert E. TI INTERNAL MEDICINE RESIDENTS' PERCEIVED RESPONSIBILITY FOR TRANSITIONS OF CARE: A NEEDS ASSESSMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Young, Eric A.; Stickrath, Chad; Burke, Robert E.] Denver VA Med Ctr, Denver, CO USA. [Gonzalo, Jed] Penn State Coll Med, Hershey, PA USA. [Kuperman, Ethan] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Smith, Christopher J.] Univ Nebraska Med Ctr, Omaha, NE USA. [Chapman, Elizabeth] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Young, Eric A.; Stickrath, Chad; Burke, Robert E.] Univ Colorado, Sch Med, Aurora, CO USA. [Calderon, Aaron] St Joseph Med Ctr, Denver, CO USA. [Lopez, Max] Univ Vermont, Burlington, VT USA. [Sweigart, Joseph R.] Univ Kentucky, Lexington, KY USA. [Theobald, Cecilia] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196402 BP S195 EP S196 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900336 ER PT J AU Zuchowski, JL Cordasco, KM Oishi, SM Rose, D Canelo, I Yano, EM Hamilton, A AF Zuchowski, Jessica L. Cordasco, Kristina M. Oishi, Sabine M. Rose, Danielle Canelo, Ismelda Yano, Elizabeth M. Hamilton, Alison TI THE USE OF TELE-MENTAL HEALTH TO ADDRESS WOMEN VETERANS' MENTAL HEALTH NEEDS IN VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Zuchowski, Jessica L.; Cordasco, Kristina M.; Oishi, Sabine M.; Rose, Danielle; Canelo, Ismelda; Yano, Elizabeth M.; Hamilton, Alison] US Dept Vet Affairs, North Hills, CA USA. [Cordasco, Kristina M.] Univ Calif Los Angeles, VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. [Yano, Elizabeth M.; Hamilton, Alison] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196274 BP S281 EP S282 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901141 ER PT J AU Zuchowski, JL Huynh, AK Stockdale, SE Meredith, LS Robles, AE Roos, P Rubenstein, LV Cordasco, KM AF Zuchowski, Jessica L. Huynh, Alexis K. Stockdale, Susan E. Meredith, Lisa S. Robles, Antonio E. Roos, Philip Rubenstein, Lisa V. Cordasco, Kristina M. TI SPECIALIST AWARENESS OF THE VA PATIENT-CENTERED MEDICAL HOME SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Rubenstein, Lisa V.] GLA VA, North Hills, CA USA. [Meredith, Lisa S.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Zuchowski, Jessica L.; Huynh, Alexis K.; Stockdale, Susan E.; Cordasco, Kristina M.] US Dept Vet Affairs, North Hills, CA USA. [Cordasco, Kristina M.] Univ Calif Los Angeles, VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. [Robles, Antonio E.; Roos, Philip] VA Loma Linda Healthcare Syst, Loma Linda, CA USA. [Robles, Antonio E.; Roos, Philip] Loma Linda Univ, Loma Linda, CA 92350 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2196239 BP S254 EP S255 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901085 ER PT J AU Ibrahim, SA AF Ibrahim, Said A. TI Patient Preference as a Barrier to Needed Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID JOINT REPLACEMENT; WILLINGNESS C1 [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Dept Vet Affairs VA, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Ibrahim, SA (reprint author), Univ Penn, Perelman Sch Med, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr ANNEX,Med, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM said.ibrahim2@va.gov FU National Institutes of Musculoskeletal and Skin Disorders [1K24AR055259-01] FX S. A. Ibrahim is supported by the National Institutes of Musculoskeletal and Skin Disorders (award 1K24AR055259-01). NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2015 VL 105 IS 4 BP 613 EP 614 DI 10.2105/AJPH.2015.302603 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM0SE UT WOS:000357387800023 PM 25713949 ER PT J AU Dunn, EC Milliren, CE Evans, CR Subramanian, SV Richmond, TK AF Dunn, Erin C. Milliren, Carly E. Evans, Clare R. Subramanian, S. V. Richmond, Tracy K. TI Disentangling the Relative Influence of Schools and Neighborhoods on Adolescents' Risk for Depressive Symptoms SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MENTAL-HEALTH; MULTILEVEL ANALYSIS; UNITED-STATES; STUDENTS; CONTEXT; RESIDENCE; OUTCOMES; SMOKING; CLIMATE; PSYCHOPATHOLOGY AB Objectives. Although schools and neighborhoods influence health, little is known about their relative importance, or the influence of one context after the influence of the other has been taken into account. We simultaneously examined the influence of each setting on depression among adolescents. Methods. Analyzing data from wave 1 (1994-1995) of the National Longitudinal Study of Adolescent Health, we used cross-classified multilevel modeling to examine between-level variation and individual-, school-, and neighborhood-level predictors of adolescent depressive symptoms. Also, we compared the results of our cross-classified multilevel models (CCMMs) with those of a multilevel model wherein either school or neighborhood was excluded. Results. In CCMMs, the school-level random effect was significant and more than 3 times the neighborhood-level random effect, even after individual-level characteristics had been taken into account. Individual-level indicators (e.g., race/ethnicity, socioeconomic status) were associated with depressive symptoms, but there was no association with either school-or neighborhood-level fixed effects. The between-level variance in depressive symptoms was driven largely by schools as opposed to neighborhoods. Conclusions. Schools appear to be more salient than neighborhoods in explaining variation in depressive symptoms. Future work incorporating cross-classified multilevel modeling is needed to understand the relative effects of schools and neighborhoods. C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Milliren, Carly E.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. [Evans, Clare R.; Subramanian, S. V.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Richmond, Tracy K.] Boston Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St,Simches Res Bldg,6th Floor, Boston, MA 02114 USA. EM edunn2@mgh.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [K01HD058042]; Robert Wood Johnson Foundation Investigator Award in Health Policy Research; NICHD [P01-HD31921] FX Research reported in this article was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; under award K01HD058042). S. V. Subramanian was supported in part by a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. We used data from the National Longitudinal Study of Adolescent Health (Add Health), a project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill and funded by NICHD (grant P01-HD31921), with cooperative funding from 23 other federal agencies and foundations. NR 67 TC 4 Z9 4 U1 1 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2015 VL 105 IS 4 BP 732 EP 740 DI 10.2105/AJPH.2014.302374 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM0SE UT WOS:000357387800043 PM 25713969 ER PT J AU Hauenstein, AV Zhang, LM Wu, H AF Hauenstein, Arthur V. Zhang, Liman Wu, Hao TI The hierarchical structural architecture of inflammasomes, supramolecular inflammatory machines SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID PYRIN DOMAIN; CRYSTAL-STRUCTURE; SIGNAL-TRANSDUCTION; AIM2 INFLAMMASOME; PROVIDES INSIGHTS; CYTOPLASMIC DNA; INNATE-IMMUNITY; ACTIVATION; PROTEIN; MECHANISM AB Inflammasomes are caspase-1 activating, molecular inflammatory machines that proteolytically mature pro-inflammatory cytokines and induce pyroptotic cell death during innate immune responses. Recent structural studies of proteins that constitute inflammasomes have yielded fresh insights into their assembly mechanisms. In particular, these include a crystal structure of the CARD-containing NOD-like receptor NLRC4, the crystallographic and electron microscopy (EM) studies of the dsDNA sensors AIM2 and IFI16, and of the regulatory protein p2027 and the cryo-EM filament structure of the PYD domain of the inflammasome adapter ASC. These data suggest inflammasome assembly that starts with ligand recognition and release of autoinhibition followed by step-wise rounds of nucleated polymerization from the sensors to the adapters, then to caspase-1. In this elegant manner, inflammasomes form by an 'all-or-none' cooperative mechanism, thereby amplifying the activation of caspase-1. The dense network of filamentous structures predicted by this model has been observed in cells as micron-sized puncta. C1 [Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Wu, H (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM hao.wu@childrens.harvard.edu FU NIH [AI050872, AI045937, AI089882] FX We apologize for incomplete coverage due to the space limitations and the vast data in the highly active field of inflammasome biology. The work was supported by grants AI050872, AI045937, and AI089882 from NIH to HW. NR 51 TC 10 Z9 10 U1 3 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2015 VL 31 BP 75 EP 83 DI 10.1016/j.sbi.2015.03.014 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CM5DC UT WOS:000357706000012 PM 25881155 ER PT J AU Hawkins, M Newman, AB Madero, M Patel, KV Shlipak, MG Cooper, J Johansen, KL Navaneethan, SD Shorr, RI Simonsick, EM Fried, LF AF Hawkins, Marquis Newman, Anne B. Madero, Magdalena Patel, Kushang V. Shlipak, Michael G. Cooper, Jennifer Johansen, Kirsten L. Navaneethan, Sankar D. Shorr, Ronald I. Simonsick, Eleanor M. Fried, Linda F. TI TV Watching, but Not Physical Activity, Is Associated With Change in Kidney Function in Older Adults SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE sedentary lifestyle; chronic disease; aged; renal health ID SERUM CYSTATIN-C; BODY-COMPOSITION; ESTIMATING GFR; SITTING TIME; HEALTH ABC; DISEASE; RISK; CKD; OBESITY; LIFE AB Background: Physical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults. Methods: The Health, Aging, and Body Composition study is a prospective cohort of 3075 well-functioning older adults. PA and television watching was measured by self-report, and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 ml/min/1.73m(2). Rapid kidney function decline was defined as an annual loss in eGFR of >3ml/min/1.73m(2). Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function. Results: Individuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI, 1.09-1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI, 1.05-1.52) compared with individuals who watched television <2 hours/day. PA was not related to either outcome. Conclusions: High levels of television watching are associated with declining kidney function; the mechanisms that underlie this association need further study. C1 [Hawkins, Marquis; Fried, Linda F.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Newman, Anne B.; Cooper, Jennifer] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez, Mexico City, DF, Mexico. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Shlipak, Michael G.; Johansen, Kirsten L.] San Francisco VA, San Francisco, CA USA. [Shlipak, Michael G.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Navaneethan, Sankar D.] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA. [Shorr, Ronald I.] Univ Florida, Dept Epidemiol, Gainseville, FL USA. [Simonsick, Eleanor M.] NIA, Baltimore, MD 21224 USA. RP Hawkins, M (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. EM mshawkins@schoolph.umass.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050, R01-AG029364]; NINR [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA Grant R01-AG028050, NIA Grant R01-AG029364, NINR Grant R01-NR012459, and the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 33 TC 0 Z9 0 U1 3 U2 5 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD APR PY 2015 VL 12 IS 4 BP 561 EP 568 DI 10.1123/jpah.2013-0289 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM7XE UT WOS:000357909000018 PM 24762526 ER PT J AU Handelsman, Y Bloomgarden, ZT Grunberger, G Umpierrez, G Zimmerman, RS Bailey, TS Blonde, L Bray, GA Cohen, AJ Dagogo-Jack, S Davidson, JA Einhorn, D Ganda, OP Garber, AJ Garvey, WT Henry, RR Hirsch, IB Horton, ES Hurley, DL Jellinger, PS Jovanovic, L Lebovitz, HE LeRoith, D Levy, P McGill, JB Mechanick, JI Mestman, JH Moghissi, ES Orzeck, EA Pessah-Pollack, R Rosenblit, PD Vinik, AI Wyne, K Zangeneh, F AF Handelsman, Yehuda Bloomgarden, Zachary T. Grunberger, George Umpierrez, Guillermo Zimmerman, Robert S. Bailey, Timothy S. Blonde, Lawrence Bray, George A. Cohen, A. Jay Dagogo-Jack, Samuel Davidson, Jaime A. Einhorn, Daniel Ganda, Om P. Garber, Alan J. Garvey, W. Timothy Henry, Robert R. Hirsch, Irl B. Horton, Edward S. Hurley, Daniel L. Jellinger, Paul S. Jovanovic, Lois Lebovitz, Harold E. LeRoith, Derek Levy, Philip McGill, Janet B. Mechanick, Jeffrey I. Mestman, Jorge H. Moghissi, Etie S. Orzeck, Eric A. Pessah-Pollack, Rachel Rosenblit, Paul D. Vinik, Aaron I. Wyne, Kathleen Zangeneh, Farhad TI AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY - CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN-2015-EXECUTIVE SUMMARY SO ENDOCRINE PRACTICE LA English DT Article ID CORONARY-HEART-DISEASE; PRIMARY PREVENTION; STANDARDIZED PRODUCTION; GLYCEMIC LOAD; RISK-FACTORS; HEALTH; RECOMMENDATIONS; METAANALYSIS; ASPIRIN; BENEFITS C1 [Handelsman, Yehuda] Metab Inst Amer, Tarzana, CA 91356 USA. [Handelsman, Yehuda] Amer Coll Endocrinol, Tarzana, CA USA. [Bloomgarden, Zachary T.] Mt Sinai Sch Med, New York, NY USA. [Grunberger, George] Wayne State Univ, Sch Med, Grunberger Diabet Inst, Bloomfield Hills, MI USA. [Grunberger, George] Wayne State Univ, Sch Med, Internal Med & Mol Med & Genet, Bloomfield Hills, MI USA. [Umpierrez, Guillermo] Emory Univ, Sch Med, Med, Atlanta, GA USA. [Umpierrez, Guillermo] Grady Hlth Syst, Endocrinol Sect, Atlanta, GA USA. [Zimmerman, Robert S.] Cleveland Clin, Endocrinol, Cleveland, OH 44106 USA. [Zimmerman, Robert S.] Cleveland Clin, Cleveland Clin Diabet Ctr, Cleveland, OH 44106 USA. [Bailey, Timothy S.] UCSD Sch Med, Escondido, CA USA. [Bailey, Timothy S.] AMCR Inst, Escondido, CA USA. [Blonde, Lawrence] Ochsner Med Ctr, Dept Endocrinol Diabet & Metab, Ochsner Diabet Clin Res Unit, New Orleans, LA USA. [Bray, George A.] Louisiana State Univ, Pennington Ctr, Med, Baton Rouge, LA 70803 USA. [Cohen, A. Jay] Endocrine Clin PC, Memphis, TN USA. [Dagogo-Jack, Samuel] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. [Davidson, Jaime A.] Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Div Endocrinol, Med, Dallas, TX 75390 USA. [Einhorn, Daniel] Amer Assoc Clin Endocrinologists, Jacksonville, FL USA. [Einhorn, Daniel] Scripps Whittier Diabet Inst, San Diego, CA USA. [Einhorn, Daniel] UCSD, Med, La Jolla, CA USA. [Ganda, Om P.] Joslin Diabet Ctr, Lipid Clin, Boston, MA 02215 USA. [Ganda, Om P.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Garber, Alan J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Garber, Alan J.] Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA. [Garber, Alan J.] Baylor Coll Med, Dept Mol Biol, Houston, TX 77030 USA. [Garber, Alan J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] UAB Diabet Res Ctr, Mt Brook, AL USA. [Henry, Robert R.] Univ Calif San Diego, Med, San Diego, CA USA. [Henry, Robert R.] VA San Diego Healthcare Syst, Sect Diabet Endocrinol & Metab, San Diego, CA USA. [Hirsch, Irl B.] Univ Washington, Sch Med, Med, Seattle, WA USA. [Horton, Edward S.] Joslin Diabet Ctr, Brookline, MA USA. [Horton, Edward S.] Harvard Univ, Sch Med, Med, Brookline, MA USA. [Hurley, Daniel L.] Mayo Clin, Med, Rochester, MN USA. [Jellinger, Paul S.] Univ Miami, Miller Sch Med, Med Clin, Miami, FL 33136 USA. [Jellinger, Paul S.] Ctr Diabet & Endocrine Care, Hollywood, FL USA. [Jovanovic, Lois] Sansum Diabet Res Inst, Santa Barbara, CA USA. [Jovanovic, Lois] Keck Sch Med USC, Med, Santa Barbara, CA USA. [Jovanovic, Lois] Santa Barbara Cty Hlth Care Serv, Santa Barbara, CA USA. [Jovanovic, Lois] Univ Calif Santa Barbara, Biomol Sci & Engn & Chem Engn, Santa Barbara, CA 93106 USA. [Lebovitz, Harold E.] SUNY Hlth Sci Ctr Brooklyn, Med, Staten Isl, NY USA. [LeRoith, Derek] Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Res, New York, NY USA. [Levy, Philip] Univ Arizona, Coll Med, Med, Banner Good Samaritan Multispecialty Grp, Phoenix, AZ USA. [McGill, Janet B.] Washington Univ, Div Endocrinol Metab & Lipid Res, Med, St Louis, MO USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Med, New York, NY 10029 USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, Metab Support, New York, NY 10029 USA. [Mestman, Jorge H.] Keck Sch Med USC, Med & Obstetr & Gynecol, Los Angeles, CA USA. [Moghissi, Etie S.] Univ Calif Los Angeles, Marina Del Rey, CA USA. [Orzeck, Eric A.] Endocrinol Associates, Houston, TX USA. [Pessah-Pollack, Rachel] Mt Sinai Sch Med, New York, NY USA. [Pessah-Pollack, Rachel] ProHealth Care Associates, Div Endocrinol, Lake Success, NY USA. [Rosenblit, Paul D.] Univ Calif Irvine, Sch Med, Med, Div Endocrinol,Diabet,Metab, Irvine, CA 92717 USA. [Rosenblit, Paul D.] UCI Med Ctr, Diabet Out Patient Clin, Orange, CA USA. [Rosenblit, Paul D.] Diabet Lipid Management & Res Ctr, Huntington Beach, CA USA. [Vinik, Aaron I.] Strelitz Diabet Ctr, Eastern Virginia Med Ctr, Med Pathol Neurobiol, Norfolk, VA USA. [Vinik, Aaron I.] Strelitz Diabet Ctr, Eastern Virginia Med Ctr, Res & Neuroendocrine Unit, Norfolk, VA USA. [Wyne, Kathleen] Houston Methodist Hosp, Weill Cornell Med Coll, Houston, TX USA. [Zangeneh, Farhad] Endocrine Diabet & Osteoporosis Clin, Sterling, VA USA. RP Handelsman, Y (reprint author), Metab Inst Amer, Tarzana, CA 91356 USA. RI Cohen, Ari/A-5799-2011 FU Boehringer Ingelheim GmbH; GlaxoSmithKline plc; Novo Nordisk A/S; Amgen Inc; Gilead; Merck Co, Inc; sanofi-aventis U.S. LLC; Intarcia Therapeutics, Inc; Lexicon Pharmaceuticals, Inc; Takeda Pharmaceutical Company Limited; Halozyme, Inc; Amarin Corporation; Amylin Pharmaceuticals, LLC; Janssen Pharmaceuticals, Inc; Vivus, Inc.; Regeneron; Bayer AG; Medtronic, Inc; BD; Abbott Laboratories; ACON Laboratories, Inc; Alere; Animas Corporation; Cebix Incorporated; Bristol-Myers Squibb Company; Dexcom, Inc; Eli Lilly and Company; Insulet Corporation; LifeScan, Inc; MannKind Corporation; Orexigen Therapeutics, Inc; Tandem Diabetes Care; Boehringer Ingelheim GmbH/Eli Lilly and Company; Sidley Austin LLP; Adams and Reese LLP; AstraZeneca; Amylin Pharmaceuticals, Inc; Weight Watchers International, Inc; Eisai Inc; Hitachi Ltd.; Andromeda Biotech Ltd; Novartis AG; Daiichi Sankyo Company, Limited; Pfizer Inc; Eisai Inc.; Isis Pharmaceuticals, Inc; Pamlab, Inc; Impeto Medical; Tercica, Inc; ViroMed Laboratories Inc; Asahi-Kasei Corporation; sanofi-aventis U.S. LLC. FX Dr. Yehuda Handelsman reports that he has received consultant/speaker fees and research grant support from Boehringer Ingelheim GmbH, GlaxoSmithKline plc, and Novo Nordisk A/S; consultant fees and research grant support from Amgen Inc, Gilead, Merck & Co, Inc, and sanofi-aventis U.S. LLC; research grant support from Intarcia Therapeutics, Inc, Lexicon Pharmaceuticals, Inc, and Takeda Pharmaceutical Company Limited; consultant fees from Halozyme, Inc; and consultant/speaker fees from Amarin Corporation, Amylin Pharmaceuticals, LLC, Janssen Pharmaceuticals, Inc, and Vivus, Inc.; Dr. Zachary Bloomgarden reports that he has received speaker honoraria from Merck & Co, Inc and Santarus, Inc; consultant honoraria from Bristol-Myers Squibb Company/AstraZeneca and Boehringer Ingelheim GmbH; speaker/consultant honoraria from Johnson & Johnson Services, Inc and Novo Nordisk A/S; stockholder earnings from Abbott Laboratories, Covidien, F. Hoffman-La Roche Ltd, Hospira Inc, Pfizer Inc, St. Jude Medical, Inc, and Zoetis; and stockholder earnings and consultant honoraria from Novartis AG.; Dr. George Grunberger reports that he has received speaker honoraria and research support for his role as investigator from Bristol-Myers Squibb Company, Eli Lilly and Company, and Novo Nordisk A/S; speaker honoraria from Amarin Corporation, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, sanofi-aventis U.S. LLC, Santarus, Inc, Takeda Pharmaceutical Company Limited, and Valeritas, Inc. Dr. Guillermo Umpierrez reports that he has received consultant honoraria and research grant support from Boehringer Ingelheim GmbH, Merck & Co, Inc, Novo Nordisk A/S, sanofi-aventis U.S. LLC, and Regeneron.; Dr. Robert S. Zimmerman reports that he has received speaker honoraria from Janssen Pharmaceuticals, Inc, Johnson & Johnson Services, Inc, Merck & Co, Inc, and Santarus, Inc; and research grant support from Novo Nordisk A/S.; Dr. Timothy Bailey reports that he has received speaker/consultant honoraria and research support from Novo Nordisk A/S; consultant honoraria and research support from Bayer AG, BD, Medtronic, Inc, and sanofi-aventis U.S. LLC; and research support from Abbott Laboratories, ACON Laboratories, Inc, Alere, Animas Corporation, Cebix Incorporated, Bristol-Myers Squibb Company, Dexcom, Inc, Eli Lilly and Company, GlaxoSmithKline plc, Halozyme, Inc, Insulet Corporation, LifeScan, Inc, MannKind Corporation, Merck & Co, Inc, Orexigen Therapeutics, Inc, and Tandem Diabetes Care.; Dr. Lawrence Blonde reports that he has received speaker/consultant honoraria and research grant support to Ochsner Medical Center for his role as investigator from Novo Nordisk A/S and sanofi-aventis U.S. LLC; research grant support to Ochsner Medical Center for his role as investigator from Eli Lilly and Company; speaker honoraria from Amylin Pharmaceuticals, LLC; speaker/consultant honoraria from AstraZeneca, Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc, and Merck & Co, Inc; and consultant honoraria from Eisai Inc, GlaxoSmithKline plc, and Quest Diagnostics Incorporated.; Dr. Alan J. Cohen reports that he has received speaker honoraria from AstraZeneca, sanofi-aventis U.S. LLC, and Takeda Pharmaceutical Company Limited; and speaker honoraria and research funding from Boehringer Ingelheim GmbH/Eli Lilly and Company, Merck & Co, Inc, and Novo Nordisk A/S.; Dr. Samuel Dagogo-Jack reports that he has received fees for his role as diabetes expert legal consultant from Sidley Austin LLP and Adams and Reese LLP; consultant honoraria from Janssen Pharmaceuticals, Inc, Merck & Co, Inc, and Santarus, Inc; consultant honoraria and research support for his role as principal investigator from Novo Nordisk A/S; and research support for his role as principal investigator from AstraZeneca and Boehringer Ingelheim GmbH.; Dr. Daniel Einhorn reports that he has received consultant honoraria from Bristol-Myers Squibb Company/AstraZeneca; consultant honoraria and research grant support from Eli Lilly and Company and Novo Nordisk A/S; consultant honoraria and shareholdings from Freedom Meditech, Inc, GlySens Incorporated, and Halozyme, Inc; consultant/speaker honoraria and research grant support from Janssen Pharmaceuticals, Inc; and research grant support from AstraZeneca, MannKind Corporation, sanofi-aventis U.S. LLC, and Takeda Pharmaceutical Company Limited.; Dr. Om Ganda reports that he has received advisory board honoraria from Amgen Inc. and sanofi-aventis U.S. LLC and research grant support from Amarin Corporation.; Dr. W. Timothy Garvey reports that he has received research support from Amylin Pharmaceuticals, Inc, Merck & Co, Inc, sanofi-aventis U.S. LLC, and Weight Watchers International, Inc; research support and advisory board honoraria from Eisai Inc; and advisory board honoraria from Alkermes plc, AstraZeneca, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Janssen Pharmaceuticals, Inc, LipoScience, Inc, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited, and Vivus, Inc.; Dr. Robert R. Henry reports that he has received research grant support from Hitachi Ltd. and sanofi-aventis U.S. LLC; consultant/advisory board honoraria from Alere, ClinMet, Eisai Inc, and Isis Pharmaceuticals, Inc; speaker honoraria from Amgen Inc, Daiichi Sankyo Company, Limited, Elcelyx Therapeutics, Inc, Merck & Co., Inc, and Vivus, Inc; consultant/advisory board/speaker honoraria from Boehringer Ingelheim GmbH, F. Hoffman-La Roche Ltd/Genentech Inc, Gilead, Intarcia Therapeutics, Inc, Johnson & Johnson Services, Inc/Janssen Pharmaceuticals, Inc, and Novo Nordisk A/S; and consultant/advisory board/speaker honoraria and research grant support from Eli Lilly and Company.; Dr. Irl B. Hirsch reports that he has received research grant support for his role as principal investigator from Halozyme, Inc and sanofi-aventis U.S. LLC; and consultant honoraria from Abbott Laboratories, BD, and F. Hoffman-La Roche Ltd.; Dr. Janet B. McGill reports that she has received speaker's bureau/consultant honoraria from Janssen Pharmaceuticals, Inc and Merck & Co, Inc; consultant honoraria and research grant support to Washington University School of Medicine from MannKind Corporation, Novo Nordisk A/S, and sanofi-aventis U.S. LLC; consultant honoraria from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, and McNEIL-PPC, Inc; and research grant support to Washington University School of Medicine from Andromeda Biotech Ltd, Intarcia Therapeutics, Inc, Novartis AG, and Takeda Pharmaceutical Company Limited.; Dr. Etie S. Moghissi reports that she has received speaker fees from Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc, Takeda Pharmaceutical Company Limited; speaker/consultant fees from Novo Nordisk A/S; and consultant fees from Amylin Pharmaceuticals, LLC, AstraZeneca, and sanofi-aventis U.S. LLC.; Dr. Paul D. Rosenblit reports that he has received speaker/advisory board honoraria from Amarin Corporation; speaker honoraria from Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, and Janssen Pharmaceuticals, Inc; advisory board honoraria and research grant support for his role as principal investigator from Dexcom, Inc; research grant support for his role as principal investigator from Amgen Inc, Daiichi Sankyo Company, Limited, Eli Lilly and Company, GlaxoSmithKline plc, MannKind Corporation, Novartis AG, Orexigen Therapeutics, Inc, Pfizer Inc, and sanofi-aventis U.S. LLC; and speaker honoraria and research grant support for his role as principal investigator from AstraZeneca, Eisai Inc., Merck & Co, Inc, Novo Nordisk A/S, and Takeda Pharmaceutical Company Limited.; Dr. Aaron I. Vinik reports that he has received consultant fees from Isis Pharmaceuticals, Inc, Merck & Co, Inc, and Pamlab, Inc; consultant fees and research grant support for his role as principal investigator from Pfizer Inc; and research grant support for his role as principal investigator from Impeto Medical, Intarcia Therapeutics, Inc, Tercica, Inc, and ViroMed Laboratories Inc.; Ms. Amanda M. Justice reports that she has received consulting fees for writing/editorial support from Asahi-Kasei Corporation and sanofi-aventis U.S. LLC. NR 38 TC 3 Z9 3 U1 1 U2 3 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD APR PY 2015 VL 21 IS 4 BP 413 EP 437 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM5MF UT WOS:000357731300013 PM 27408942 ER PT J AU Hotokezaka, Y Katayama, I van Leyen, K Nakamura, T AF Hotokezaka, Y. Katayama, I. van Leyen, K. Nakamura, T. TI GSK-3 beta-dependent downregulation of gamma-taxilin and alpha NAC merge to regulate ER stress responses SO CELL DEATH & DISEASE LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; POLYPEPTIDE-ASSOCIATED COMPLEX; UBIQUITIN-PROTEASOME SYSTEM; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; BINDING-PROTEIN; MESSENGER-RNA; MOUSE MODEL; CELL-DEATH AB The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3 beta (GSK-3 beta)-dependent downregulation of gamma-taxilin and nascent polypeptide-associated complex alpha-subunit (alpha NAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic and autophagic pathways. The degradation of gamma-taxilin or alpha NAC was sufficient to initiate UPRs in normoxic cells. However, the ER stress signaling pathways initiated by gamma-taxilin or alpha NAC were distinct, triggering different ER stress sensors and activating different downstream pathways. Hypoxia caused GSK-3 beta-dependent tau hyperphosphorylation and cleavage in neuronal cells, but gamma-taxilin ablation induced tau hyperphosphorylation alone and alpha NAC ablation induced neither changes. Notably, downregulation of gamma-taxilin and alpha NAC occurs in the brain of patients with Alzheimer's disease. These results suggest that GSK-3 beta-dependent downregulation of gamma-taxilin and alpha NAC, which differently activate the UPRs, merge to regulate hypoxia-induced ER stress responses and provide a new insight into the pathogenesis of neurodegenerative diseases. C1 [Hotokezaka, Y.; Katayama, I.; Nakamura, T.] Nagasaki Univ, Sch Dent, Dept Radiol & Canc Biol, Nagasaki 8528588, Japan. [van Leyen, K.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. [van Leyen, K.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. [van Leyen, K.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Nakamura, T (reprint author), Nagasaki Univ, Sch Dent, Dept Radiol & Canc Biol, 1-7-1 Sakamoto, Nagasaki 8528588, Japan. EM taku@nagasaki-u.ac.jp FU [24390421]; [25462921] FX We thank Dr Joo Eun Jung for her help with performing the immunohistochemistry. This study was supported by Grant-in-Aids for Scientific Research of TN (24390421) and YH (25462921). NR 53 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD APR PY 2015 VL 6 AR e1719 DI 10.1038/cddis.2015.90 PG 10 WC Cell Biology SC Cell Biology GA CM2LL UT WOS:000357511500012 PM 25880086 ER PT J AU Kataoka, K Matsumoto, H Kaneko, H Notomi, S Takeuchi, K Sweigard, JH Atik, A Murakami, Y Connor, KM Terasaki, H Miller, JW Vavvas, DG AF Kataoka, K. Matsumoto, H. Kaneko, H. Notomi, S. Takeuchi, K. Sweigard, J. H. Atik, A. Murakami, Y. Connor, K. M. Terasaki, H. Miller, J. W. Vavvas, D. G. TI Macrophage- and RIP3-dependent inflammasome activation exacerbates retinal SO CELL DEATH & DISEASE LA English DT Article ID PHOTORECEPTOR CELL-DEATH; MIXED LINEAGE KINASE; MACULAR DEGENERATION; NLRP3 INFLAMMASOME; SUBRETINAL FLUID; PROGRAMMED NECROSIS; CASPASE ACTIVATION; MESSENGER-RNA; RIP3 KINASE; RAT-BRAIN AB Detachment of photoreceptors from the retinal pigment epithelium is seen in various retinal disorders, resulting in photoreceptor death and subsequent vision loss. Cell death results in the release of endogenous molecules that activate molecular platforms containing caspase-1, termed inflammasomes. Inflammasome activation in retinal diseases has been reported in some cases to be protective and in others to be detrimental, causing neuronal cell death. Moreover, the cellular source of inflammasomes in retinal disorders is not clear. Here, we demonstrate that patients with photoreceptor injury by retinal detachment (RD) have increased levels of cleaved IL-1 beta, an end product of inflammasome activation. In an animal model of RD, photoreceptor cell death led to activation of endogenous inflammasomes, and this activation was diminished by Rip3 deletion. The major source of Il1b expression was found to be infiltrating macrophages in the subretinal space, rather than dying photoreceptors. Inflammasome inhibition attenuated photoreceptor death after RD. Our data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases. C1 [Kataoka, K.; Matsumoto, H.; Notomi, S.; Takeuchi, K.; Sweigard, J. H.; Atik, A.; Murakami, Y.; Connor, K. M.; Miller, J. W.; Vavvas, D. G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA USA. [Kataoka, K.; Kaneko, H.; Terasaki, H.] Nagoya Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 466, Japan. RP Vavvas, DG (reprint author), Massachusetts Eye & Ear Infirm, Angiogenesis Lab, 325 Cambridge St, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu RI Terasaki, Hiroko/M-5054-2014; Kaneko, Hiroki/O-7695-2015; Kataoka, Keiko/B-2806-2016 OI Kaneko, Hiroki/0000-0003-0731-6465; Kataoka, Keiko/0000-0002-8795-6536 FU NEI [R21EY023079-01A1, EY014104]; Yeatts Family Foundation; Loefflers Family Fund; Macula Society; Bausch & Lomb Vitreoretinal Fellowship; Physician Scientist Award; Research to Prevent Blindness Foundation; NIH [R01EY022084-01/S1] FX We thank Tetsu Asami, MD, PhD, Takeshi Iwase, MD, PhD, and Yasuki Ito, MD, PhD, for their assistance in the collection of patients' samples. We also thank Wendy Chao, PhD for her support in critical review. This work was supported by: NEI R21EY023079-01A1 (DGV); The Yeatts Family Foundation (DGV, JWM); The Loefflers Family Fund (DGV, JWM); the 2013 Macula Society Research Grant award (DGV); Bausch & Lomb Vitreoretinal Fellowship (HM); a Physician Scientist Award (DGV), an unrestricted grant (JWM) from the Research to Prevent Blindness Foundation; NIH R01EY022084-01/S1 (KMC), and NEI grant EY014104 (MEEI Core Grant). NR 67 TC 3 Z9 4 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD APR PY 2015 VL 6 AR e1731 DI 10.1038/cddis.2015.73 PG 10 WC Cell Biology SC Cell Biology GA CM2LL UT WOS:000357511500024 PM 25906154 ER PT J AU Mauris, J Dieckow, J Schob, S Pulli, B Hatton, MP Jeong, S Bauskar, A Gabison, E Nowak, R Arguso, P AF Mauris, J. Dieckow, J. Schob, S. Pulli, B. Hatton, M. P. Jeong, S. Bauskar, A. Gabison, E. Nowak, R. Argueso, P. TI Loss of CD147 results in impaired epithelial cell differentiation and malformation of the meibomian gland SO CELL DEATH & DISEASE LA English DT Article ID DRY-EYE DISEASE; BRANCHING MORPHOGENESIS; EXTRACELLULAR-MATRIX; INTERNATIONAL WORKSHOP; EXPRESSION; METALLOPROTEINASES; PROLIFERATION; CANCER; EMMPRIN/CD147; STIMULATION AB Meibomian gland dysfunction is a leading cause of ocular surface disease. However, little is known about the regulatory processes that control the development and maintenance of this sebaceous gland. Here, we identify a novel function for CD147, a transmembrane protein that promotes tissue remodeling through induction of matrix metalloproteinases, in regulating meibocyte differentiation and activity. We found that CD147 localized along basal cells and within discrete membrane domains of differentiated meibocytes in glandular acini containing gelatinolytic activity. Induction of meibocyte differentiation in vitro promoted CD147 clustering and MMP9 secretion, whereas RNAi-mediated abrogation of CD147 impaired MMP9 secretion, concomitant with a reduction in the number of proliferative cells and cytoplasmic lipids. Meibomian glands of CD147 knockout mice had a lower number of acini in both the superior and inferior tarsal plates of the eyelids, and were characterized by loss of lipid-filled meibocytes compared with control mice. Together, our data provide evidence showing that gelatinolytic activity in meibocytes is dependent on CD147, and supports a role for CD147 in maintaining the normal development and function of the meibomian gland. C1 [Mauris, J.; Dieckow, J.; Hatton, M. P.; Argueso, P.] Harvard Univ, Sch Med, Schepens Eye Res Inst & Massachusetts Eye & Ear, Boston, MA USA. [Schob, S.; Pulli, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Hatton, M. P.] Ophthalm Consultants Boston, Boston, MA USA. [Jeong, S.; Bauskar, A.] Univ So Calif, Keck Sch Med, Inst Genet Med, Los Angeles, CA 90033 USA. [Jeong, S.] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. [Bauskar, A.] Univ So Calif, Keck Sch Med, Grad Program Med Biol, Los Angeles, CA 90033 USA. [Gabison, E.] Univ Paris VII Diderot, APHP, Hop Bichat, Cornea & External Dis,Fdn A De Rothschild, Paris, France. [Nowak, R.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA. RP Arguso, P (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM pablo_argueso@meei.harvard.edu FU NIH [EY014847, EY024031]; ARVO Foundation/Vistakon Dry Eye Research Fellowship; MD fellowship by the Boehringer Ingelheim Fonds; Foundation for Basic Research in Medicine, Germany; Sicca Forschungsforderung of the Association of German Ophthalmologists; Research to Prevent Blindness FX This work has been supported by NIH Grants EY014847 and EY024031 to PA and an ARVO Foundation/Vistakon Dry Eye Research Fellowship to JM. JD was supported through a MD fellowship by the Boehringer Ingelheim Fonds, Foundation for Basic Research in Medicine, Germany, and by the Sicca Forschungsforderung of the Association of German Ophthalmologists. SJ was supported through an unrestricted grant from Research to Prevent Blindness to the University of Southern California. We would like to thank Ashley Woodward, Christina Kaiser-Marko, Ann Tisdale, Balaraj Menon, and Wendy R. Kam for their skillful assistance and advice. We also thank David A. Sullivan for generously providing the hTERT-immortalized human meibomian gland epithelial cell line, and M. Elizabeth Fini for critical reading of the manuscript. NR 39 TC 3 Z9 3 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD APR PY 2015 VL 6 AR e1726 DI 10.1038/cddis.2015.98 PG 8 WC Cell Biology SC Cell Biology GA CM2LL UT WOS:000357511500019 PM 25880093 ER PT J AU Thrift, AP Gong, J Peters, U Chang-Claude, J Rudolph, A Slattery, ML Chan, AT Esko, T Wood, AR Yang, J Vedantam, S Gustafsson, S Pers, TH Baron, JA Bezieau, S Kury, S Ogino, S Berndt, SI Casey, G Haile, RW Du, MM Harrison, TA Thornquist, M Duggan, DJ Le Marchand, L Lemire, M Lindor, NM Seminara, D Song, MY Thibodeau, SN Cotterchio, M Win, AK Jenkins, MA Hopper, JL Ulrich, CM Potter, JD Newcomb, PA Schoen, RE Hoffmeister, M Brenner, H White, E Hsu, L Campbell, PT AF Thrift, Aaron P. Gong, Jian Peters, Ulrike Chang-Claude, Jenny Rudolph, Anja Slattery, Martha L. Chan, Andrew T. Esko, Tonu Wood, Andrew R. Yang, Jian Vedantam, Sailaja Gustafsson, Stefan Pers, Tune H. Baron, John A. Bezieau, Stephane Kuery, Sebastien Ogino, Shuji Berndt, Sonja I. Casey, Graham Haile, Robert W. Du, Mengmeng Harrison, Tabitha A. Thornquist, Mark Duggan, David J. Le Marchand, Loic Lemire, Mathieu Lindor, Noralane M. Seminara, Daniela Song, Mingyang Thibodeau, Stephen N. Cotterchio, Michelle Win, Aung Ko Jenkins, Mark A. Hopper, John L. Ulrich, Cornelia M. Potter, John D. Newcomb, Polly A. Schoen, Robert E. Hoffmeister, Michael Brenner, Hermann White, Emily Hsu, Li Campbell, Peter T. CA GIANT Consortium TI Mendelian randomization study of height and risk of colorectal cancer SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Body height; colorectal cancer; epidemiology ID GENOME-WIDE ASSOCIATION; COLON-CANCER; BODY-SIZE; UNITED-STATES; INSTRUMENTAL VARIABLES; GENETIC EPIDEMIOLOGY; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; RECTAL-CANCER; WOMEN AB Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies. C1 [Thrift, Aaron P.; Gong, Jian; Peters, Ulrike; Du, Mengmeng; Harrison, Tabitha A.; Thornquist, Mark; Potter, John D.; Newcomb, Polly A.; White, Emily; Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Thrift, Aaron P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Thrift, Aaron P.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Peters, Ulrike; Potter, John D.; Newcomb, Polly A.; White, Emily] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Boston Childrens Hosp, Ctr Basic Translat Obes Res, Boston, MA USA. [Esko, Tonu; Pers, Tune H.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Broad Inst, Cambridge, MA USA. [Wood, Andrew R.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England. [Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Yang, Jian] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia. [Yang, Jian] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Gustafsson, Stefan] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Casey, Graham] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Haile, Robert W.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Duggan, David J.] Translat Genom Res Inst, Phoenix, AZ USA. [Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. [Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Song, Mingyang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada. [Win, Aung Ko; Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Ulrich, Cornelia M.] Populat Sci Huntsman Canc Inst, Salt Lake City, UT USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. [Hoffmeister, Michael; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Hsu, Li] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. RP Thrift, AP (reprint author), Baylor Coll Med, Dan L Duncan Canc Ctr, One Baylor Plaza,MS BCM305, Houston, TX 77030 USA. EM aaron.thrift@bcm.edu RI Song, Mingyang/M-6701-2013; Bezieau, stephane/G-5621-2015; KURY, Sebastien/G-5971-2015; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; Hoffmeister, Michael/B-5745-2012 OI Song, Mingyang/0000-0002-1324-0316; Bezieau, stephane/0000-0003-0095-1319; KURY, Sebastien/0000-0001-5497-0465; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Esko, Tonu/0000-0003-1982-6569; Yang, Jian/0000-0003-2001-2474; Win, Aung Ko/0000-0002-2794-5261; Hoffmeister, Michael/0000-0002-8307-3197 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; National Institutes of Health (RFA) [CA-95-011]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Institutes of Health [R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, P50 CA 127003, R01 CA137178, P01 CA 087969, R01 CA151993, R01 CA042182, U01 CA074783, K05 CA154337]; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research, through Ontario Ministry of Research and Innovation; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH) [U01 HG004446, GEI U01 HG 004438]; Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN 268201100046C, HHSN268201100001C, HHSN2682011000 02C, HHSN268201100003C, HHSN268201100004C, HHS N271201100004C] FX This work is supported by grants to GECCO and CCFR, as well as by grants to the individual studies (as noted below). The funders of the study had no role in the design, analysis or interpretation of the data, or in writing or publication decisions related to this article.; GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).; CCFR: National Institutes of Health (RFA # CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators. This genome-wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CFR. The following Colon CFR centres contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783) and the Seattle Colorectal Cancer Family Registry (U01 CA074794).; DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS: National Institutes of Health (R01 CA48998 to M.L.S).; H.P.F.S. is supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993 and P50 CA 127003), N.H.S. by the National Institutes of Health (R01 CA137178, P01 CA 087969, R01 CA151993 and P50 CA 127003,) and P.H.S. by the National Institutes of Health (R01 CA042182).; OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.; PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager M et al. Nat Genet 2007;39:645-49), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir L et al. Nat Genet 2009;41:986-90 and Petersen GM et al. Nat Genet 2010;42:224-28), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (R01 CA076366 to P.A.N.). VITAL: National Institutes of Health (K05 CA154337).; VITAL: National Institutes of Health (K05 CA154337). WHI: The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN 268201100046C, HHSN268201100001C, HHSN2682011000 02C, HHSN268201100003C, HHSN268201100004C and HHS N271201100004C. NR 39 TC 10 Z9 10 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2015 VL 44 IS 2 BP 662 EP 672 DI 10.1093/ije/dyv082 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL6VO UT WOS:000357106100028 PM 25997436 ER PT J AU McNeil, MR Pratt, SR Szuminsky, N Sung, JE Fossett, TRD Fassbinder, W Lim, KY AF McNeil, Malcolm R. Pratt, Sheila R. Szuminsky, Neil Sung, Jee Eun Fossett, Tepanta R. D. Fassbinder, Wiltrud Lim, Kyoung Yuel TI Reliability and Validity of the Computerized Revised Token Test: Comparison of Reading and Listening Versions in Persons With and Without Aphasia SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID SPEEDED CLASSIFICATION; VISUAL DOMINANCE; COMPREHENSION; IMPAIRMENTS; INDIVIDUALS; PERFORMANCE; MODALITY; STIMULUS; SPEECH; PEOPLE AB Purpose: This study assessed the reliability and validity of intermodality associations and differences in persons with aphasia (PWA) and healthy controls (HC) on a computerized listening and 3 reading versions of the Revised Token Test (RTT; McNeil & Prescott, 1978). Method: Thirty PWA and 30 HC completed the test versions, including a complete replication. Reading versions varied according to stimulus presentation method: (a) full-sentence presentation, (b) self-paced word-by-word fullsentence construction, and (c) self-paced word-by-word presentation with each word removed with the onset of the next word. Participants also received tests of aphasia and reading severity. Results: The listening version produced higher overall mean scores than each of the reading versions. Differences were small and within 1 standard error of measurement of each version. Overall score test-retest reliability among versions for PWA ranged from r =.89 to r = .97. Correlations between the listening and reading versions ranged from r = .79 to r = .85. All versions correlated highly with aphasia and reading severity. Correlations were generally low for the HC due to restricted variability. Factor analysis yielded a 2-factor solution for PWA and a single-factor for HC. Conclusions: Intermodality differences were small, and all 4 versions were reliable, concurrently valid, and sensitive to similar linguistic processing difficulties in PWA. C1 [McNeil, Malcolm R.; Pratt, Sheila R.; Szuminsky, Neil; Sung, Jee Eun; Fossett, Tepanta R. D.; Fassbinder, Wiltrud; Lim, Kyoung Yuel] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [McNeil, Malcolm R.; Pratt, Sheila R.; Szuminsky, Neil; Sung, Jee Eun; Fossett, Tepanta R. D.; Fassbinder, Wiltrud; Lim, Kyoung Yuel] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP McNeil, MR (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. EM mcneil@pitt.edu FU VA Hospital, Denver, CO; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service [C47074X, C3118R] FX The previously published test on which this research is based is derived from McNeil and Prescott (1978), and those data are based on work supported in part by the VA Hospital, Denver, CO. Additional support for the work reported here are based in part on funding supplied by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service (award #C47074X to Malcolm R. McNeil and award #C3118R to Patrick J. Doyle and Sheila R. Pratt), and resources and facilities provided by the Geriatric Research Education and Clinical Center in the Veterans Affairs Pittsburgh Healthcare System, PA. The contents of this article do not represent the views of the Department of Veterans Affairs or the U.S. Government. NR 46 TC 2 Z9 2 U1 2 U2 7 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 EI 1558-9102 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD APR PY 2015 VL 58 IS 2 BP 311 EP 324 DI 10.1044/2015_JSLHR-L-13-0030 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA CL6ZF UT WOS:000357118000012 PM 25569547 ER PT J AU Molis, MR Kampel, SD McMillan, GP Gallun, FJ Dann, SM Konrad-Martin, D AF Molis, Michelle R. Kampel, Sean D. McMillan, Garnett P. Gallun, Frederick J. Dann, Serena M. Konrad-Martin, Dawn TI Effects of Hearing and Aging on Sentence-Level Time-Gated Word Recognition SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID SPEECH RECOGNITION; PROCESSING SPEED; GATING PARADIGM; AGE; ADULTS; NOISE; SENSITIVITY; PERCEPTION; PERFORMANCE; RECEPTION AB Purpose: Aging is known to influence temporal processing, but its relationship to speech perception has not been clearly defined. To examine listeners' use of contextual and phonetic information, the Revised Speech Perception in Noise test (R-SPIN) was used to develop a time-gated word (TGW) task. Method: In Experiment 1, R-SPIN sentence lists were matched on context, target-word length, and median word segment length necessary for target recognition. In Experiment 2, TGW recognition was assessed in quiet and in noise among adults of various ages with normal hearing to moderate hearing loss. Linear regression models of the minimum word duration necessary for correct identification and identification failure rates were developed. Age and hearing thresholds were modeled as continuous predictors with corrections for correlations among multiple measurements of the same participants. Results: While aging and hearing loss both had significant impacts on task performance in the most adverse listening condition (low context, in noise), for most conditions, performance was limited primarily by hearing loss. Conclusion: Whereas hearing loss was strongly related to target-word recognition, the effect of aging was only weakly related to task performance. These results have implications for the design and evaluation of studies of hearing and aging. C1 [Molis, Michelle R.; Kampel, Sean D.; McMillan, Garnett P.; Gallun, Frederick J.; Dann, Serena M.; Konrad-Martin, Dawn] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. [Molis, Michelle R.; Gallun, Frederick J.; Konrad-Martin, Dawn] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Molis, MR (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA. EM Michelle.Molis@va.gov FU Veterans Affairs Rehabilitation Research & Development Service [C7450R, C7113N, C6116W, C4963W]; National Center for Rehabilitative Auditory Research FX This work was supported by Veterans Affairs Rehabilitation Research & Development Service Grants C7450R, C7113N, C6116W, C4963W, and the National Center for Rehabilitative Auditory Research. Thanks to Kelly Reavis, Roger Ellingson, and Patrick Tsukuda for their work on this project. NR 35 TC 4 Z9 4 U1 0 U2 1 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 EI 1558-9102 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD APR PY 2015 VL 58 IS 2 BP 481 EP 496 DI 10.1044/2015_JSLHR-H-14-0098 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA CL6ZF UT WOS:000357118000026 PM 25815688 ER PT J AU Ekeroma, A Camargo, C Scragg, R Wall, C Stewart, A Mitchell, E Crane, J Grant, C AF Ekeroma, A. Camargo, C. Scragg, R. Wall, C. Stewart, A. Mitchell, E. Crane, J. Grant, C. TI Predictors of vitamin D status in pregnant women in New Zealand SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Meeting Abstract C1 [Ekeroma, A.; Scragg, R.; Wall, C.; Stewart, A.; Mitchell, E.; Grant, C.] Univ Auckland, Auckland 1, New Zealand. [Camargo, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Crane, J.] Univ Otago, Wellington, New Zealand. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD APR PY 2015 VL 122 SU 1 SI SI MA EP2.06 BP 7 EP 8 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL1OJ UT WOS:000356713000016 ER PT J AU Foldager, CB Nyengaard, JR Lind, M Spector, M AF Foldager, Casper Bindzus Nyengaard, Jens Randel Lind, Martin Spector, Myron TI A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue SO CARTILAGE LA English DT Article DE cartilage repair; stereology; histomorphometry; histology ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; CHONDRAL DEFECTS; ARTICULAR-CARTILAGE; SCORING SYSTEM; CANINE MODEL; MICROFRACTURE; HISTOLOGY; THICKNESS; KNEE; NEUROPATHOLOGY AB Objective: To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design: Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin-eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results: We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm(3) (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion: We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. C1 [Foldager, Casper Bindzus; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Orthopaed Res, Boston, MA 02115 USA. [Foldager, Casper Bindzus; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA USA. [Foldager, Casper Bindzus] Aarhus Univ Hosp, Orthopaed Res Lab, Inst Clin Med, DK-8000 Aarhus C, Denmark. [Nyengaard, Jens Randel] Aarhus Univ, Ctr Stochast Geometry & Adv Bioimaging, Stereol & EM Lab, Aarhus, Denmark. [Lind, Martin] Aarhus Univ Hosp, Sports Trauma Clin, DK-8000 Aarhus C, Denmark. RP Foldager, CB (reprint author), Aarhus Univ Hosp, Orthopaed Res Lab, Norrebrogade 44,Bldg 1A, DK-8000 Aarhus C, Denmark. EM foldager@clin.au.dk FU U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; Elite Research Scholarship from the Danish Minister of Science, Technology and Innovation; Villum Foundation FX The authors would like to thank the six blinded observers participating the evaluation. We would also like to thank Niels Trolle, Department of Biostatistics, Aarhus University, for assisting in the description of interobserver variability. The research reported here was supported, in part, by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. A postdoctoral research fellowship for CBF by an Elite Research Scholarship from the Danish Minister of Science, Technology and Innovation. Centre for Stochastic Geometry and Advanced Bioimaging is supported by Villum Foundation. NR 43 TC 4 Z9 4 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD APR PY 2015 VL 6 IS 2 BP 123 EP 132 DI 10.1177/1947603514560655 PG 10 WC Orthopedics SC Orthopedics GA CL0KK UT WOS:000356631400007 PM 26069715 ER PT J AU Sawaya, H Johnson, K Schmidt, M Arana, A Chahine, G Atoui, M Pincus, D George, MS Panksepp, J Nahas, Z AF Sawaya, Helen Johnson, Kevin Schmidt, Matthew Arana, Ashley Chahine, George Atoui, Mia Pincus, David George, Mark S. Panksepp, Jaak Nahas, Ziad TI Resting-State Functional Connectivity of Antero-Medial Prefrontal Cortex Sub-Regions in Major Depression and Relationship to Emotional Intelligence SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE anterior medial PFC; emotional intelligence; major depression; MSCEIT; resting state functional connectivity ID DEFAULT MODE NETWORK; SOMATIC MARKER HYPOTHESIS; TREATMENT RESPONSE; DISORDER; MOOD; TRAIT AB Background: Major depressive disorder has been associated with abnormal resting-state functional connectivity (FC), especially in cognitive processing and emotional regulation networks. Although studies have found abnormal FC in regions of the default mode network (DMN), no study has investigated the FC of specific regions within the anterior DMN based on cytoarchitectonic subdivisions of the antero-medial pre-frontal cortex (PFC). Studies from different areas in the field have shown regions within the anterior DMN to be involved in emotional intelligence. Although abnormalities in this region have been observed in depression, the relationship between the ventromedial PFC (vmPFC) function and emotional intelligence has yet to be investigated in depressed individuals. Methods: Twenty-one medication-free, non-treatment resistant, depressed patients and 21 healthy controls underwent a resting state functional magnetic resonance imaging session. The participants also completed an ability-based measure of emotional intelligence: the Mayer-Salovey-Caruso Emotional Intelligence Test. FC maps of Brodmann areas (BA) 25, 10m, 10r, and 10p were created and compared between the two groups. Results: Mixed-effects analyses showed that the more anterior seeds encompassed larger areas of the DMN. Compared to healthy controls, depressed patients had significantly lower connectivity between BA10p and the right insula and between BA25 and the perigenual anterior cingulate cortex. Exploratory analyses showed an association between vmPFC connectivity and emotional intelligence. Conclusions: These results suggest that individuals with depression have reduced FC between antero-medial PFC regions and regions involved in emotional regulation compared to control subjects. Moreover, vmPFC functional connectivity appears linked to emotional intelligence. C1 [Sawaya, Helen; Chahine, George; Atoui, Mia; Nahas, Ziad] Amer Univ Beirut, Dept Psychiat, Beirut 2020, Lebanon. [Johnson, Kevin] Stanford Univ, Stanford, CA 94305 USA. [Schmidt, Matthew; Arana, Ashley; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC USA. [Schmidt, Matthew; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Pincus, David] Cleveland Psychoanalyt Ctr Ohio, CWRU, Dept Psychiat, Cleveland, OH USA. [Pincus, David] Cleveland Psychoanalyt Ctr Ohio, CWRU, Dept Psychol, Cleveland, OH USA. [Panksepp, Jaak] Washington State Univ, Dept Integrat Physiol & Neurosci Washington, Pullman, WA 99164 USA. RP Nahas, Z (reprint author), Amer Univ Beirut, Box 11-0236,Riad El Solh 1107, Beirut 2020, Lebanon. EM zn17@aub.edu.lb FU National Institute of Mental Health, the Brain and Behavior Research Foundation; Hope for Depression Research Foundation; American University of Beirut's Intramural Funds; Medtronic Inc.; Massachusetts Emergency Care Training Academy; Pfizer; Centre National de la Recherche Scientifique FX This research was supported by grants from the National Institute of Mental Health, the Brain and Behavior Research Foundation (formally known as National Alliance of Research on Schizophrenia and Depression), the Hope for Depression Research Foundation, American University of Beirut's Intramural Funds, Medtronic Inc., Massachusetts Emergency Care Training Academy, Pfizer, and Centre National de la Recherche Scientifique. NR 50 TC 3 Z9 3 U1 4 U2 8 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 APR PY 2015 VL 18 IS 6 DI 10.1093/ijnp/pyu112 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CL1JY UT WOS:000356700000014 ER PT J AU Avis, NE Crawford, SL Greendale, G Bromberger, JT Everson-Rose, SA Gold, EB Hess, R Joffe, H Kravitz, HM Tepper, PG Thurston, RC AF Avis, Nancy E. Crawford, Sybil L. Greendale, Gail Bromberger, Joyce T. Everson-Rose, Susan A. Gold, Ellen B. Hess, Rachel Joffe, Hadine Kravitz, Howard M. Tepper, Ping G. Thurston, Rebecca C. CA Study Womens Hlth Nation SWAN TI Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition SO JAMA INTERNAL MEDICINE LA English DT Article ID MIDDLE-AGED WOMEN; QUALITY-OF-LIFE; HOT FLASHES; MULTIETHNIC COHORT; PHYSICAL-ACTIVITY; NATION SWAN; HEALTH; QUESTIONNAIRE; FLUSHES; ANXIETY AB IMPORTANCE The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES To determine total duration of frequent VMS (>= 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS The Study of Women's Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, > 11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women. C1 [Avis, Nancy E.] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Crawford, Sybil L.] Univ Massachusetts, Med Ctr, Dept Med, Div Prevent & Behav Med, Worcester, MA USA. [Greendale, Gail] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Los Angeles, CA 90095 USA. [Bromberger, Joyce T.; Tepper, Ping G.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Everson-Rose, Susan A.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Gold, Ellen B.] Univ Calif Davis, UC Davis Sch Med, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. [Hess, Rachel] Univ Utah, Sch Hlth Sci, Dept Med, Salt Lake City, UT USA. [Joffe, Hadine] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. [Thurston, Rebecca C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Avis, NE (reprint author), Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM navis@wakehealth.edu FU National Institutes of Health [U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495]; Department of Health and Human Services; National Institute on Aging; National Institute of Nursing Research; Office of Research on Women's Health FX The Study of Women's Health Across the Nation (SWAN) has grant support (grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495) from the National Institutes of Health, Department of Health and Human Services, National Institute on Aging, National Institute of Nursing Research, and Office of Research on Women's Health. NR 49 TC 67 Z9 69 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2015 VL 175 IS 4 BP 531 EP 539 DI 10.1001/jamainternmed.2014.8063 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FJ UT WOS:000356177100013 PM 25686030 ER PT J AU Greysen, SR Cenzer, IS Auerbach, AD Covinsky, KE AF Greysen, S. Ryan Cenzer, Irena Stijacic Auerbach, Andrew D. Covinsky, Kenneth E. TI Functional Impairment and Hospital Readmission in Medicare Seniors SO JAMA INTERNAL MEDICINE LA English DT Article ID OLDER-ADULTS; RISK; HOME; ELDERS; DISABILITY; PREDICTION; DEPENDENCE; MORTALITY; ADMISSION; DISCHARGE AB IMPORTANCE Medicare currently penalizes hospitals for high readmission rates for seniors but does not account for common age-related syndromes, such as functional impairment. OBJECTIVE To assess the effects of functional impairment on Medicare hospital readmissions given the high prevalence of functional impairments in community-dwelling seniors. DESIGN, SETTING, AND PARTICIPANTS We created a nationally representative cohort of 7854 community-dwelling seniors in the Health and Retirement Study, with 22 289 Medicare hospitalizations from January 1, 2000, through December 31, 2010. MAIN OUTCOMES AND MEASURES Outcome was 30-day readmission assessed by Medicare claims. The main predictor was functional impairment determined from the Health and Retirement Study interview preceding hospitalization, stratified into the following 5 levels: no functional impairments, difficulty with 1 or more instrumental activities of daily living, difficulty with 1 or more activities of daily living (ADL), dependency (need for help) in 1 to 2 ADLs, and dependency in 3 or more ADLs. Adjustment variables included age, race/ethnicity, sex, annual income, net worth, comorbid conditions (Elixhauser score from Medicare claims), and prior admission. We performed multivariable logistic regression to adjust for clustering at the patient level to characterize the association of functional impairments and readmission. RESULTS Patients had a mean (SD) age of 78.5 (7.7) years (range, 65-105 years); 58.4% were female, 84.9% were white, 89.6% reported 3 or more comorbidities, and 86.0% had 1 or more hospitalizations in the previous year. Overall, 48.3% had some level of functional impairment before admission, and 15.5% of hospitalizations were followed by readmission within 30 days. We found a progressive increase in the adjusted risk of readmission as the degree of functional impairment increased: 13.5% with no functional impairment, 14.3% with difficulty with 1 or more instrumental activities of daily living (odds ratio [OR], 1.06; 95% CI, 0.94-1.20), 14.4% with difficulty with 1 or more ADL (OR, 1.08; 95% CI, 0.96-1.21), 16.5% with dependency in 1 to 2 ADLs (OR, 1.26; 95% CI, 1.11-1.44), and 18.2% with dependency in 3 or more ADLs (OR, 1.42; 95% CI, 1.20-1.69). Subanalysis restricted to patients admitted with conditions targeted by Medicare (ie, heart failure, myocardial infarction, and pneumonia) revealed a parallel trend with larger effects for the most impaired (16.9% readmission rate for no impairment vs 25.7% for dependency in 3 or more ADLs [OR, 1.70; 95% CI, 1.04-2.78]). CONCLUSIONS AND RELEVANCE Functional impairment is associated with increased risk of 30-day all-cause hospital readmission in Medicare seniors, especially those admitted for heart failure, myocardial infarction, or pneumonia. Functional impairment may be an important but underaddressed factor in preventing readmissions for Medicare seniors. C1 [Greysen, S. Ryan; Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94113 USA. [Cenzer, Irena Stijacic; Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr Med, San Francisco, CA 94113 USA. [Cenzer, Irena Stijacic; Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Greysen, SR (reprint author), Univ Calif San Francisco, Div Hosp Med, 533 Parnassus Ave,POB 0131, San Francisco, CA 94113 USA. EM ryan.greysen@ucsf.edu FU National Institutes of Health (NIH), National Institute of Aging (NIA) through the Claude D. Pepper Older Americans Independence Center [P30AG021342 NIH/NIA]; NIH-NIA; NIA; National Institute for Nursing Research; [1K23AG045338-01] FX Dr Greysen is supported by the National Institutes of Health (NIH), National Institute of Aging (NIA) through the Claude D. Pepper Older Americans Independence Center (grant P30AG021342 NIH/NIA), a Career Development Award (grant 1K23AG045338-01), and the NIH-NIA Loan Repayment Program. Dr Covinsky is supported by the NIA through a K-24 Career Mentoring Award and an R01 from the National Institute for Nursing Research. NR 38 TC 27 Z9 27 U1 4 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2015 VL 175 IS 4 BP 559 EP 565 DI 10.1001/jamainternmed.2014.7756 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FJ UT WOS:000356177100019 PM 25642907 ER PT J AU Jena, AB Goldman, DP Seabury, SA AF Jena, Anupam B. Goldman, Dana P. Seabury, Seth A. TI Incidence of Sexually Transmitted Infections After Human Papillomavirus Vaccination Among Adolescent Females SO JAMA INTERNAL MEDICINE LA English DT Article ID HPV VACCINATION; CERVICAL-CANCER; YOUNG-WOMEN; PARENTAL ATTITUDES; NATIONAL-SURVEY; UNITED-STATES; INTENTION; DRUGS; PREVALENCE; KNOWLEDGE AB IMPORTANCE Human papillomavirus (HPV) vaccination rates among US females remain low, in part because of concerns that HPV vaccination may promote unsafe sexual activity by lowering perceived risks of acquiring a sexually transmitted infection (STI). OBJECTIVE To study whether HPV vaccination of females is associated with increases in STI rates. DESIGN, SETTING, AND PARTICIPANTS Using a large, longitudinal insurance database of females aged 12 to 18 years insured from January 1, 2005, through December 31, 2010, in the United States, we examined whether HPV vaccination was associated with an increase in incident STIs among females who were vaccinated compared with those who were not. We defined STIs as one or more medical claims for any of the following infections in a given quarter: chlamydia, gonorrhea, herpes, human immunodeficiency virus or AIDS, or syphilis. We used difference-in-difference analysis to compare changes in STI rates among HPV-vaccinated females before and after vaccination (index quarter) to changes among age-matched nonvaccinated females before and after the index quarter. We analyzed whether effects varied according to age and prior contraceptive medication use. MAIN OUTCOMES AND MEASURES Rates of STIs. RESULTS The rates of STIs in the year before vaccination were higher among HPV-vaccinated females (94 of 21 610, 4.3 per 1000) compared with age-matched nonvaccinated females (522 of 186 501, 2.8 per 1000) (adjusted odds ratio, 1.37; 95% CI, 1.09-1.71; P =.007). The rates of STIs increased for the vaccinated (147 of 21 610, 6.8 per 1000) and nonvaccinated (781 of 186 501, 4.2 per 1000) groups in the year after vaccination (adjusted odds ratio, 1.50; 95% CI, 1.25-1.79; P <.001). The difference-in-difference odds ratio was 1.05 (95% CI, 0.80-1.38; P =.74), implying that HPV vaccination was not associated with an increase in STIs relative to growth among nonvaccinated females. Similar associations held among subgroups aged 12 through 14 years and aged 15 through 18 years and among females with contraceptive use in the index quarter. CONCLUSIONS AND RELEVANCE Human papillomavirus vaccination was not associated with increases in STIs in a large cohort of females, suggesting that vaccination is unlikely to promote unsafe sexual activity. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.; Goldman, Dana P.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Goldman, Dana P.; Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Seabury, Seth A.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU National Institutes of Health [1DP5OD017897-01]; National Institute of Aging [5P01AG033559] FX This study was funded by grant 1DP5OD017897-01 from the National Institutes of Health (Early Independence Award) (Dr Jena) and grant 5P01AG033559 from the National Institute of Aging (Drs Goldman and Seabury). NR 41 TC 19 Z9 19 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2015 VL 175 IS 4 BP 617 EP 623 DI 10.1001/jamainternmed.2014.7886 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FJ UT WOS:000356177100030 PM 25664968 ER PT J AU Bachhuber, MA Saloner, B Barry, CL AF Bachhuber, Marcus A. Saloner, Brendan Barry, Colleen L. TI What Ecologic Analyses Cannot Tell Us About Medical Marijuana Legalization and Opioid Pain Medication Mortality Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID INDIVIDUALS C1 [Bachhuber, Marcus A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.; Barry, Colleen L.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Saloner, Brendan; Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Saloner, Brendan; Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP Bachhuber, MA (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, 423 Guardian Dr,1303-A Blockley Hall, Philadelphia, PA 19104 USA. EM marcus.bachhuber@gmail.com OI Bachhuber, Marcus/0000-0002-5610-8382 NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2015 VL 175 IS 4 BP 656 EP 657 DI 10.1001/jamainternmed.2014.8027 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FJ UT WOS:000356177100057 PM 25844749 ER PT J AU Joffe, H LaCroix, AZ Cohen, L AF Joffe, Hadine LaCroix, Andrea Z. Cohen, Lee TI Concern About the Use of Venlafaxine to Treat Vasomotor Symptoms Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID EVENTS C1 [Joffe, Hadine] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Joffe, Hadine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Hadine; Cohen, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, MsFLASH Data Coordinating Ctr, Seattle, WA 98104 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family & Preventat Med, San Diego, CA 92103 USA. RP Joffe, H (reprint author), Brigham & Womens Hosp, Dept Psychiat, Womens Hormones & Aging Res Program, 75 Francis St, Boston, MA 02115 USA. EM hjoffe@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2015 VL 175 IS 4 BP 658 EP 659 DI 10.1001/jamainternmed.2014.7997 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CK4FJ UT WOS:000356177100061 PM 25844753 ER PT J AU Zakeri, K Rose, BS D'Amico, AV Jeong, JH Mell, LK AF Zakeri, Kaveh Rose, Brent S. D'Amico, Anthony V. Jeong, Jong-Hyeon Mell, Loren K. TI Competing events and costs of clinical trials: Analysis of a randomized trial in prostate cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Costs; Clinical trials; Competing events ID RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; DRUG DEVELOPMENT; END-POINTS; RISK; INNOVATION; MORTALITY; POPULATION; EFFICIENCY; CHALLENGE AB Background: Clinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. Methods: We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. Results: The treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23-0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30-0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39-1.23, vs. HR 0.94; 95% CI, 0.68-1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36-0.82, vs. HR 0.77; 95% CI, 0.58-1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30% shorter (8.4 vs. 12.0 years). Conclusion: Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Zakeri, Kaveh; Mell, Loren K.] Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA. [Rose, Brent S.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Cambridge, MA 02138 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jeong, Jong-Hyeon] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. RP Mell, LK (reprint author), Univ Calif San Diego, Dept Radiat Med & Appl Sci, 3855 Hlth Sci Dr,MC0843, La Jolla, CA 92093 USA. EM lmell@ucsd.edu OI Jeong, Jong/0000-0003-0596-2201 FU NIH National Research Service Award (NRSA) FX NIH National Research Service Award (NRSA) T32 Training Grant (Kaveh Zakeri). NR 38 TC 1 Z9 1 U1 5 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2015 VL 115 IS 1 BP 114 EP 119 DI 10.1016/j.radonc.2015.03.018 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CL1WT UT WOS:000356736300021 PM 25857696 ER PT J AU Green, J Yule, C Berger, A Weisbord, S AF Green, Jamie Yule, Christina Berger, Andrea Weisbord, Steven TI PATIENT PERSPECTIVES ON CHRONIC KIDNEY DISEASE SELF-MANAGEMENT SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of National-Kidney-Foundation CY MAR 25-29, 2015 CL Grapevine, TX SP Natl Kidney Fdn C1 [Green, Jamie; Yule, Christina; Berger, Andrea] Geisinger Med Ctr, Danville, PA 17822 USA. [Weisbord, Steven] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2015 VL 65 IS 4 MA 98 BP A39 EP A39 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CJ9BE UT WOS:000355796500101 ER PT J AU Judy, T Anita, M Rajeev, R AF Judy, Tan Anita, Mehrotra Rajeev, Rohatgi TI TELENEPHROLOGY FOR THE REMOTE MANAGEMENT OF CHRONIC KIDNEY DISEASE: A RETROSPECTIVE COHORT STUDY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of National-Kidney-Foundation CY MAR 25-29, 2015 CL Grapevine, TX SP Natl Kidney Fdn C1 [Judy, Tan; Anita, Mehrotra; Rajeev, Rohatgi] Mt Sinai Hosp, New York, NY 10029 USA. [Rajeev, Rohatgi] James J Peters VAMC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2015 VL 65 IS 4 MA 275 BP A83 EP A83 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CJ9BE UT WOS:000355796500278 ER PT J AU Nelson, J Yule, C Berger, A Weisbord, S Green, J AF Nelson, Jessica Yule, Christina Berger, Andrea Weisbord, Steven Green, Jamie TI PREVALENCE AND CORRELATES OF MEDICATION ADHERENCE IN PATIENTS WITH CHRONIC KIDNEY DISEASE SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of National-Kidney-Foundation CY MAR 25-29, 2015 CL Grapevine, TX SP Natl Kidney Fdn C1 [Nelson, Jessica; Yule, Christina; Berger, Andrea; Green, Jamie] Geisinger Med Ctr, Danville, PA 17822 USA. [Weisbord, Steven] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2015 VL 65 IS 4 MA 184 BP A60 EP A60 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CJ9BE UT WOS:000355796500187 ER PT J AU Nelson, J Yule, C Berger, A Weisbord, S Green, J AF Nelson, Jessica Yule, Christina Berger, Andrea Weisbord, Steven Green, Jamie TI ASSOCIATION OF HEALTH LITERACY WITH MEDICATION SELF-MANAGEMENT SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of National-Kidney-Foundation CY MAR 25-29, 2015 CL Grapevine, TX SP Natl Kidney Fdn C1 [Nelson, Jessica; Yule, Christina; Berger, Andrea; Green, Jamie] Geisinger Med Ctr, Danville, PA 17822 USA. [Weisbord, Steven] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2015 VL 65 IS 4 MA 183 BP A60 EP A60 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CJ9BE UT WOS:000355796500186 ER PT J AU Sultan, G Agarwal, G Dah, K Wagner, B Werner, S AF Sultan, G. Agarwal, G. Dah, K. Wagner, B. Werner, S. TI IMMUNOTACTOID GLOMERULOPATHY WITH MEMBRANOUS PATTERN IN PATIENT WITH RHEUMATOID ARTHRITIS AND MONOCLONAL GAMMOPATHY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of National-Kidney-Foundation CY MAR 25-29, 2015 CL Grapevine, TX SP Natl Kidney Fdn C1 Univ Texas San Antonio, Dept Nephrol, San Antonio, TX USA. Univ Texas San Antonio, Dept Pathol, San Antonio, TX USA. South Texas Vet Hlth Care Syst, Dept Nephrol, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2015 VL 65 IS 4 MA 271 BP A82 EP A82 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CJ9BE UT WOS:000355796500274 ER PT J AU Lidz, CW Albert, K Appelbaum, P Dunn, LB Overton, E Pivovarova, E AF Lidz, Charles W. Albert, Karen Appelbaum, Paul Dunn, Laura B. Overton, Eve Pivovarova, Ekaterina TI Why Is Therapeutic Misconception So Prevalent? SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article DE therapeutic misconception; informed consent; clinical trials; research ethics ID INFORMED-CONSENT; TRIALS AB Therapeutic misconception (TM)-when clinical research participants fail to adequately grasp the difference between participating in a clinical trial and receiving ordinary clinical care-has long been recognized as a significant problem in consent to clinical trials. We suggest that TM does not primarily reflect inadequate disclosure or participants' incompetence. Instead, TM arises from divergent primary cognitive frames. The researchers' frame places the clinical trial in the context of scientific designs for assessing intervention efficacy. In contrast, most participants have a cognitive frame that is personal and focused primarily on their medical problems. To illustrate this, we draw on interview material from both clinical researchers and participants in clinical trials. We suggest that reducing TM requires encouraging subjects to adjust their frame, not just add information to their existing frame. What is necessary is a scientific reframing of participation in a clinical trial. C1 [Lidz, Charles W.] Univ Massachusetts, Sch Med, Psychiat, Worcester, MA 01602 USA. [Albert, Karen] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Appelbaum, Paul] Columbia Univ Coll Phys & Surg, Psychiat Med & Law, New York, NY 10032 USA. [Appelbaum, Paul] Columbia Univ Coll Phys & Surg, Div Law Eth & Psychiat, New York, NY 10032 USA. [Appelbaum, Paul] Columbia Univ Coll Phys & Surg, Dept Psychiat, Ctr Res Eth Legal & Social Implicat Psychiat, Neurol & Behav Genet, New York, NY 10032 USA. [Dunn, Laura B.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Dunn, Laura B.] Univ Calif San Francisco, Sch Med, Psychooncol, San Francisco, CA 94143 USA. [Overton, Eve] Yale Univ, Sch Med, New Haven, CT USA. [Pivovarova, Ekaterina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Law Brain & Behav, Cambridge, MA 02138 USA. RP Lidz, CW (reprint author), Univ Massachusetts, Sch Med, Psychiat, Worcester, MA 01602 USA. FU NINR [5RC1NR011612] FX The authors thank Scott Kim, M.D., Ph.D., and Katy Downs for their assistance with data collection. No author has any material or financial conflicts of interest. The study discussed in this article was funded by NINR Grant #5RC1NR011612. NR 21 TC 6 Z9 6 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0963-1801 EI 1469-2147 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD APR PY 2015 VL 24 IS 2 BP 231 EP 241 DI 10.1017/S096318011400053X PG 11 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA CK4CF UT WOS:000356166100012 PM 25719358 ER PT J AU Chan, JM Wong, KHK Richards, AM Drum, CL AF Chan, Juliana M. Wong, Keith H. K. Richards, Arthur Mark Drum, Chester L. TI Microengineering in cardiovascular research: new developments and translational applications SO CARDIOVASCULAR RESEARCH LA English DT Review DE Microengineering; vascular models; point-of-care diagnostics; microfluidics; three-dimensional cell culture ID MYOCARDIAL-INFARCTION; IN-VITRO; MICROFLUIDIC SYSTEMS; THROMBUS FORMATION; DRUG DEVELOPMENT; HEART-FAILURE; ANIMAL-MODELS; SHEAR-STRESS; BLOOD; DISEASE AB Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease. In recent years, advances in technical fabrication and biological integration have provided new insights into biological phenomena, improved diagnostic measurements, and made major steps towards de novo tissue creation. Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics. With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community. C1 [Chan, Juliana M.] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 639798, Singapore. [Chan, Juliana M.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Wong, Keith H. K.] Harvard Univ, Sch Med, Ctr Engn Med, Cambridge, MA 02138 USA. [Wong, Keith H. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Cambridge, MA 02138 USA. [Richards, Arthur Mark; Drum, Chester L.] Natl Univ Singapore, Yong Loo Lin Sch Med, Cardiovasc Res Inst, Singapore 117595, Singapore. RP Drum, CL (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Cardiovasc Res Inst, Singapore 117595, Singapore. EM mdccld@nus.edu.sg RI Drum, Chester/A-6089-2015; Chan, Juliana/E-8646-2014; Wong, Keith/J-6857-2012 OI Drum, Chester/0000-0001-6327-4584; Chan, Juliana/0000-0002-7489-3716; Wong, Keith/0000-0002-6578-0373 FU Nanyang Technological University (NTU); Lee Kong Chian School of Medicine (LKCMedicine); National Medical Research Council (NMRC) Clinical Scientist Award (CSA); National University of Singapore (NUS); National University Health System (NUHS) FX J.M.C. acknowledges start-up grant funding from Nanyang Technological University (NTU) and the Lee Kong Chian School of Medicine (LKCMedicine). C.L.D. acknowledges funding from the National Medical Research Council (NMRC) Clinical Scientist Award (CSA), and funding from the National University of Singapore (NUS) and National University Health System (NUHS). NR 64 TC 3 Z9 3 U1 6 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD APR 1 PY 2015 VL 106 IS 1 BP 9 EP 18 DI 10.1093/cvr/cvv049 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK4GP UT WOS:000356182400007 PM 25691539 ER PT J AU Mayer, EL Dominici, LS AF Mayer, Erica L. Dominici, Laura S. TI Breast Cancer Axillary Staging: Much Ado About Micrometastatic Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID LYMPH-NODE DISSECTION; SENTINEL-NODE; LOCOREGIONAL RECURRENCE; TRIAL; SUBTYPE; BIOPSY; WOMEN; CHEMOTHERAPY; MORBIDITY; RECEPTOR C1 [Mayer, Erica L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dominici, Laura S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Mayer, EL (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 23 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 EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2015 VL 33 IS 10 BP 1095 EP 1097 DI 10.1200/JCO.2014.59.2303 PG 3 WC Oncology SC Oncology GA CK2QZ UT WOS:000356057900003 PM 25713441 ER PT J AU Irwin, ML Cartmel, B Gross, CP Ercolano, E Li, FY Yao, XP Fiellin, M Capozza, S Rothbard, M Zhou, Y Harrigan, M Sanft, T Schmitz, K Neogi, T Hershman, D Ligibel, J AF Irwin, Melinda L. Cartmel, Brenda Gross, Cary P. Ercolano, Elizabeth Li, Fangyong Yao, Xiaopan Fiellin, Martha Capozza, Scott Rothbard, Marianna Zhou, Yang Harrigan, Maura Sanft, Tara Schmitz, Kathryn Neogi, Tuhina Hershman, Dawn Ligibel, Jennifer TI Randomized Exercise Trial of Aromatase Inhibitor-Induced Arthralgia in Breast Cancer Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; JOINT SYMPTOMS; CLINICAL-PRACTICE; THERAPY; OUTCOMES; ACUPUNCTURE; TAMOXIFEN; KNEE; PAIN AB Purpose Arthralgia occurs in up to 50% of breast cancer survivors treated with aromatase inhibitors (AIs) and is the most common reason for poor AI adherence. We conducted, in 121 breast cancer survivors receiving an AI and reporting arthralgia, a yearlong randomized trial of the impact of exercise versus usual care on arthralgia severity. Patients and Methods Eligibility criteria included receiving an AI for at least 6 months, reporting >= 3 of 10 for worst joint pain on the Brief Pain Inventory (BPI), and reporting < 90 minutes per week of aerobic exercise and no strength training. Participants were randomly assigned to exercise (150 minutes per week of aerobic exercise and supervised strength training twice per week) or usual care. The BPI, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were completed at baseline and at 3, 6, 9, and 12 months. Intervention effects were evaluated using mixed-model repeated measures analysis, with change at 12 months as the primary end point. Results Over 12 months, women randomly assigned to exercise (n = 61) attended 70% (+/- standard deviation [SD], 28%) of resistance training sessions and increased their exercise by 159 (+/- SD, 136) minutes per week. Worst joint pain scores decreased by 1.6 points (29%) at 12 months among women randomly assigned to exercise versus a 0.2-point increase (3%) among those receiving usual care (n = 60; P < .001). Pain severity and interference, as well as DASH and WOMAC pain scores, also decreased significantly at 12 months in women randomly assigned to exercise, compared with increases for those receiving usual care (all P < .001). Conclusion Exercise led to improvement in AI-induced arthralgia in previously inactive breast cancer survivors. (C) 2014 by American Society of Clinical Oncology C1 [Irwin, Melinda L.; Cartmel, Brenda; Gross, Cary P.; Ercolano, Elizabeth; Li, Fangyong; Yao, Xiaopan; Fiellin, Martha; Capozza, Scott; Rothbard, Marianna; Zhou, Yang; Harrigan, Maura; Sanft, Tara] Yale Univ, New Haven, CT 06520 USA. [Irwin, Melinda L.; Cartmel, Brenda; Gross, Cary P.; Ercolano, Elizabeth; Li, Fangyong; Yao, Xiaopan; Zhou, Yang; Sanft, Tara] Yale Canc Ctr, New Haven, CT USA. [Schmitz, Kathryn] Univ Penn, Philadelphia, PA 19104 USA. [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ligibel, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hershman, Dawn] Columbia Univ, New York, NY USA. RP Irwin, ML (reprint author), Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu OI Neogi, Tuhina/0000-0002-9515-1711 FU National Cancer Institute [R01 CA132931]; Breast Cancer Research Foundation; Yale Cancer Center [P30 CA016359]; Clinical and Translational Science Award from the National Center for Advancing Translational Science, a component of the National Institutes of Health [UL1 TR000142] FX Supported by National Cancer Institute Grant No. R01 CA132931 and in part by a grant from the Breast Cancer Research Foundation (M.L.I.), Yale Cancer Center Support Grant No. P30 CA016359, and Clinical and Translational Science Award Grant No. UL1 TR000142 from the National Center for Advancing Translational Science, a component of the National Institutes of Health. Certain data used in this study were obtained from the Connecticut Tumor Registry, located in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. NR 33 TC 25 Z9 26 U1 1 U2 15 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 APR 1 PY 2015 VL 33 IS 10 BP 1104 EP 1111 DI 10.1200/JCO.2014.57.1547 PG 8 WC Oncology SC Oncology GA CK2QZ UT WOS:000356057900006 PM 25452437 ER PT J AU Krop, IE Suter, TM Dang, CT Dirix, L Romieu, G Zamagni, C Citron, ML Campone, M Xu, N Smitt, M Gianni, L AF Krop, Ian E. Suter, Thomas M. Dang, Chau T. Dirix, Luc Romieu, Gilles Zamagni, Claudio Citron, Marc L. Campone, Mario Xu, Na Smitt, Melanie Gianni, Luca TI Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo) Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRIAL COMPARING DOXORUBICIN; NSABP B-31; OPEN-LABEL; PROGNOSTIC-SIGNIFICANCE; FOLLOW-UP; PACLITAXEL; N9831; PERTUZUMAB; HERA AB Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) >= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety. Results Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (>= 10 percentage points from baseline to LVEF< 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received >= one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed >= 95% of the planned radiation dose with delay <= 5 days. Conclusion Use of T-DM1 for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive EBC, providing support for phase III trials of T-DM1 in this setting. (C) 2015 by American Society of Clinical Oncology C1 [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Suter, Thomas M.] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Dang, Chau T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Citron, Marc L.] Hofstra North Shore Long Isl Jewish Sch Med, New Hyde Pk, NY USA. [Dirix, Luc] St Augustinus Hosp, Antwerp, Belgium. [Romieu, Gilles] Inst Canc Montpellier Val dAurelle, Montpellier, France. [Campone, Mario] Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. [Zamagni, Claudio] Policlin St Orsola Malpighi Hosp, Bologna, Italy. [Gianni, Luca] Hosp San Raffaele, I-20132 Milan, Italy. [Xu, Na; Smitt, Melanie] Genentech Inc, San Francisco, CA 94080 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, Breast Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ian_krop@dfci.harvard.edu FU Genentech, a member of the Roche group FX Supported by Genentech, a member of the Roche group, which also funded third-party writing assistance. NR 30 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2015 VL 33 IS 10 BP 1136 EP 1142 DI 10.1200/JCO.2014.58.7782 PG 7 WC Oncology SC Oncology GA CK2QZ UT WOS:000356057900010 PM 25713436 ER PT J AU Lu-Emerson, C Duda, DG Emblem, KE Taylor, JW Gerstner, ER Loeffler, JS Batchelor, TT Jain, RK AF Lu-Emerson, Christine Duda, Dan G. Emblem, Kyrre E. Taylor, Jennie W. Gerstner, Elizabeth R. Loeffler, Jay S. Batchelor, Tracy T. Jain, Rakesh K. TI Lessons From Anti-Vascular Endothelial Growth Factor and Anti-Vascular Endothelial Growth Factor Receptor Trials in Patients With Glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BEVACIZUMAB PLUS IRINOTECAN; PROGRESSION-FREE SURVIVAL; RECURRENT GLIOBLASTOMA; MULTIFORME; CANCER; VEGF AB Treatment of glioblastoma (GBM), the most common primary malignant brain tumor in adults, remains a significant unmet need in oncology. Historically, cytotoxic treatments provided little durable benefit, and tumors recurred within several months. This has spurred a substantial research effort to establish more effective therapies for both newly diagnosed and recurrent GBM. In this context, antiangiogenic therapy emerged as a promising treatment strategy because GBMs are highly vascular tumors. In particular, GBMs overexpress vascular endothelial growth factor (VEGF), a proangiogenic cytokine. Indeed, many studies have demonstrated promising radiographic response rates, delayed tumor progression, and a relatively safe profile for anti-VEGF agents. However, randomized phase III trials conducted to date have failed to show an overall survival benefit for antiangiogenic agents alone or in combination with chemoradiotherapy. These results indicate that antiangiogenic agents may not be beneficial in unselected populations of patients with GBM. Unfortunately, biomarker development has lagged behind in the process of drug development, and no validated biomarker exists for patient stratification. However, hypothesis-generating data from phase II trials that reveal an association between increased perfusion and/or oxygenation (ie, consequences of vascular normalization) and survival suggest that early imaging biomarkers could help identify the subset of patients who most likely will benefit from anti-VEGF agents. In this article, we discuss the lessons learned from the trials conducted to date and how we could potentially use recent advances in GBM biology and imaging to improve outcomes of patients with GBM who receive antiangiogenic therapy. (C) 2015 by American Society of Clinical Oncology C1 [Lu-Emerson, Christine; Duda, Dan G.; Emblem, Kyrre E.; Taylor, Jennie W.; Gerstner, Elizabeth R.; Loeffler, Jay S.; Batchelor, Tracy T.; Jain, Rakesh K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lu-Emerson, Christine; Duda, Dan G.; Emblem, Kyrre E.; Taylor, Jennie W.; Gerstner, Elizabeth R.; Loeffler, Jay S.; Batchelor, Tracy T.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), 100 Blossom St,Cox-734, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012 OI Emblem, Kyrre/0000-0002-6580-9519 FU National Institutes of Health (NIH) [R01CA129371, K24CA125440A, P01CA080124, R01CA163815, R01CA159258]; Proton Beam/Federal Share Program; National Foundation for Cancer Research; Merck; Norwegian Research Council [191088/V50]; South-Eastern Norway Regional Health Authority [2013069]; NIH from the Harvard Clinical and Translational Science Center (National Center for Research Resources) [8UL1TR000170-05]; NIH from the Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences) [8UL1TR000170-05]; Harvard University and its affiliated academic health care centers FX Supported by Grants No. R01CA129371 and K24CA125440A (T.T.B.), P01CA080124 and R01CA163815 (R.K.J.), and R01CA159258 (D.G.D.) from the National Institutes of Health (NIH); the Proton Beam/Federal Share Program (R.K.J and D.G.D.); the National Foundation for Cancer Research (R.K.J.); funding from Merck (E.R.G.); Grant No. 191088/V50 from the Norwegian Research Council; Grant No. 2013069 from the South-Eastern Norway Regional Health Authority (K.E.E.); NIH Award No. 8UL1TR000170-05 from the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences), and by Harvard University and its affiliated academic health care centers. NR 11 TC 32 Z9 32 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2015 VL 33 IS 10 BP 1197 EP 1213 DI 10.1200/JCO.2014.55.9575 PG 17 WC Oncology SC Oncology GA CK2QZ UT WOS:000356057900019 PM 25713439 ER PT J AU Usman, MW Luo, F Cheng, HL Zhao, JJ Liu, PX AF Usman, Muhammad Waqas Luo, Fuwen Cheng, Hailing Zhao, Jean J. Liu, Pixu TI Chemopreventive effects of aspirin at a glance SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Aspirin; Cancer; Chemoprevention; Cyclooxygenase ID LOW-DOSE ASPIRIN; RANDOMIZED CONTROLLED-TRIALS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER CELLS; POPULATION-BASED COHORT; NF-KAPPA-B; COLORECTAL-CANCER; PROSTAGLANDIN E-2; PROSTATE-CANCER; BREAST-CANCER AB Experimental, epidemiological, and clinical data from the last two decades have each supported the hypothesis that aspirin possesses anticancer properties, and that its use may also reduce the lifetime probability of developing or dying from a number of cancers. Aspirin's ability to act on multiple key metabolic and signaling pathways via inhibition of the cyclooxygenase (COX) enzyme, as well as through COX-independent mechanisms, makes it particularly relevant in the fight against cancer. A growing body of evidence indicates that aspirin may not only reduce cancer risk, but also prevent metastasis and angiogenesis while slowing the rate of mutation-inducing DNA damage. These emerging benefits of aspirin are offset to some extent by the known risks of treatment, such as cardiovascular events and gastrointestinal bleeding. However, it has been shown that pre-treatment risk assessment of individual patients and the use of proton pump inhibitors or Helicobacter pylori eradication therapy concomitantly with aspirin treatment can reduce these potential risks. Thus, the significant benefits of aspirin treatment, coupled with recent data concerning its risks, may prove to tip the balance in favor of aspirin use in cancer prevention. (C) 2015 Elsevier B.V. All rights reserved. C1 [Usman, Muhammad Waqas; Cheng, Hailing; Liu, Pixu] Dalian Med Univ, Affiliated Hosp 2, Inst Canc, Dalian, Liaoning, Peoples R China. [Usman, Muhammad Waqas; Liu, Pixu] Dalian Med Univ, Inst Canc Stem Cell, Dalian, Liaoning, Peoples R China. [Luo, Fuwen] Dalian Med Univ, Affiliated Hosp 2, Dept Acute Abdomen Surg, Dalian, Liaoning, Peoples R China. [Cheng, Hailing; Zhao, Jean J.; Liu, Pixu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Cheng, Hailing; Zhao, Jean J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Cheng, HL (reprint author), Dalian Med Univ, Affiliated Hosp 2, Inst Canc, Dalian, Liaoning, Peoples R China. EM hailing_cheng@dfci.harvard.edu; jean_zhao@dfci.harvard.edu; Pixu_liu@dlmedu.edu.cn FU Chinese Government Scholarship [CSC 2013422002]; National Natural Science Foundation of China [81372853, 81472447]; Liaoning Provincial Climbing Scholars Supporting Program of China; Program for Changjiang Scholars and Innovative Research Team in University [IRT13049]; Liaoning Provincial Natural Science Foundation of China [502537] FX This work was supported by the Chinese Government Scholarship (CSC 2013422002 to M.W. Usman), National Natural Science Foundation of China (No. 81372853 to P. Liu, No. 81472447 to H. Cheng), Liaoning Provincial Climbing Scholars Supporting Program of China (2012 to P. Liu and 2014 to H. Cheng), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13049 to P. Liu), and Liaoning Provincial Natural Science Foundation of China (No. 502537 to P. Liu). NR 106 TC 16 Z9 16 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR PY 2015 VL 1855 IS 2 BP 254 EP 263 DI 10.1016/j.bbcan.2015.03.007 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA CJ3EO UT WOS:000355366400012 PM 25842298 ER PT J AU Kedrin, D Gala, MK AF Kedrin, Dmitriy Gala, Manish K. TI Genetics of the Serrated Pathway to Colorectal Cancer SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Editorial Material ID TUMOR PROGRESSION; SENESCENCE; TUMORIGENESIS; MUTATIONS; RELATIVES; RISKS; RNF43 C1 [Kedrin, Dmitriy; Gala, Manish K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Kedrin, Dmitriy; Gala, Manish K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gala, MK (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, GRJ 720N, Boston, MA 02114 USA. EM mgala@mgh.harvard.edu OI Kedrin, Dmitriy/0000-0001-6093-7282 FU NIDDK NIH HHS [T32 DK007191, K23 DK103119] NR 12 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD APR PY 2015 VL 6 AR e84 DI 10.1038/ctg.2015.12 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5YL UT WOS:000355570000002 PM 25856207 ER PT J AU Abramovitch, A Cooperman, A AF Abramovitch, Amitai Cooperman, Allison TI The cognitive neuropsychology of obsessive-compulsive disorder: A critical review SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Review DE OCD; Neuropsychology; Executive functions; Controversies; Cognitive ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE METABOLIC RATES; MEDIAL FRONTAL-CORTEX; SYMPTOM DIMENSIONS; UNIPOLAR DEPRESSION; RESPONSE-INHIBITION; EXECUTIVE FUNCTION; NONVERBAL MEMORY; MOTOR INHIBITION AB For over a quarter century, a substantial body of literature investigating neuropsychological test performance in obsessive-compulsive disorder (OCD) has yielded inconsistent results. Thus, it has been continuously challenging to draw conclusions regarding an OCD-specific neuropsychological profile. In this comprehensive review of the neuropsychological literature in OCD, we critically review neuropsychological test performance by domain, as well as potential moderators of neuropsychological functions, proposed endophenotypes, neuropsychological predictors of treatment response, and contemporary controversies in the field. Previous qualitative/systematic reviews of this body of literature have repeatedly noted its inconsistency, concluding that more research is needed. Unfortunately, the accumulation of neuropsychological research is OCD has not yet promoted our ability to draw conclusions about a distinct neuropsychological profile of OCD. Thus, we conclude this review with novel suggestions for future investigations. (C) 2015 Elsevier Inc, All rights reserved. C1 [Abramovitch, Amitai] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Abramovitch, Amitai; Cooperman, Allison] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Abramovitch, Amitai] Texas State Univ, Dept Psychol, San Marcos, TX 78666 USA. RP Abramovitch, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM aabramovitch@mgh.harvard.edu; abramovitch@txstate.edu OI Abramovitch, Amitai/0000-0001-9640-0970 NR 178 TC 13 Z9 13 U1 13 U2 46 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD APR PY 2015 VL 5 BP 24 EP 36 DI 10.1016/j.jocrd.2015.01.002 PG 13 WC Psychiatry SC Psychiatry GA CJ3GT UT WOS:000355372100004 ER PT J AU Binh, TT Suzuki, R Trang, TTH Kwon, DH Yamaoka, Y AF Tran Thanh Binh Suzuki, Rumiko Tran Thi Huyen Trang Kwon, Dong Hyeon Yamaoka, Yoshio TI Search for Novel Candidate Mutations for Metronidazole Resistance in Helicobacter pylori Using Next-Generation Sequencing SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RDXA GENE; ANTIBIOTIC-RESISTANCE; CLARITHROMYCIN RESISTANCE; PROTEIN-SYNTHESIS; STRAIN 908; ERADICATION; INFECTION; FRXA; GENOME; NITROREDUCTASE AB Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance. C1 [Tran Thanh Binh; Suzuki, Rumiko; Tran Thi Huyen Trang; Yamaoka, Yoshio] Oita Univ, Fac Med, Dept Environm & Prevent Med, Yufu, Japan. [Tran Thanh Binh] Cho Ray Hosp, Dept Endoscopy, Ho Chi Minh City, Vietnam. [Kwon, Dong Hyeon] Long Isl Univ, Dept Biol, Brooklyn, NY USA. [Yamaoka, Yoshio] Baylor Coll Med, Dept Med Gastroenterol, Houston, TX 77030 USA. [Yamaoka, Yoshio] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Oita Univ, Fac Med, Dept Environm & Prevent Med, Yufu, Japan. EM yyamaoka@oita-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [25293104, 24659200, 24406015]; Special Co-ordination Funds for Promoting Science and Technology from the MEXT of Japan; National Institutes of Health [DK62813, GM94053]; Japanese Government (Monbukagakusho, MEXT) Scholarship Program FX This study was supported by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (25293104, 24659200, and 24406015) (to Y.Y.), the Special Co-ordination Funds for Promoting Science and Technology from the MEXT of Japan (to Y.Y.), and National Institutes of Health grants DK62813 (to Y.Y.) and GM94053 (to D.H.K.). T.T.B. is a doctoral student supported by the Japanese Government (Monbukagakusho, MEXT) Scholarship Program for 2010. NR 59 TC 9 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2015 VL 59 IS 4 BP 2343 EP 2348 DI 10.1128/AAC.04852-14 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CI8BY UT WOS:000354993700061 PM 25645832 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Future directions in the treatment of cholangiocarcinoma SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE Cholangiocarcinoma; Resection; Liver transplantation; Liver-directed therapy; Chemotherapy; Targeted therapy ID BILIARY-TRACT CANCER; ISOCITRATE DEHYDROGENASE 1; SEER DATABASE ANALYSIS; INTRAHEPATIC CHOLANGIOCARCINOMA; MULTIINSTITUTIONAL ANALYSIS; HILAR CHOLANGIOCARCINOMA; TARGETED THERAPY; GEMCITABINE; MUTATIONS; OXALIPLATIN AB Cholangiocarcinoma (CCA) comprises a heterogeneous group of cancers with pathologic features of biliary tract differentiation, and is best classified anatomically as intrahepatic CCA (ICC), perihilar (pCCA), or distal (dCCA) CCA. They represent a clinically and genetically diverse collection of cancers. Surgical resection represents the only curative modality for CCA, although there are encouraging data with liver transplantation for early stage pCCA. There is no established adjuvant therapy for CCA. Unfortunately, most patients with CCA will present with unresectable or metastatic disease with poor prognosis. Currently the combination of gemcitabine and cisplatin remains the standard therapy for advanced CCA. No second line therapy has definitely demonstrated improved survival benefits. Development of molecularly targeted therapies in advanced CCA remains challenging. However, recent efforts with targeted and whole exome sequencing have defined the landscape of mutations underlying CCA, particularly ICC. The identification of novel molecular signatures in CCA coupled with molecularly targeted therapy development provides the potential for developing novel therapeutic options in this intractable disease. (C) 2015 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Tucker Gosnell Ctr Gastrointestinal Canc, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Tucker Gosnell Ctr Gastrointestinal Canc, Massachusetts Gen Hosp,Canc Ctr, 55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 38 TC 7 Z9 7 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6918 EI 1532-1916 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD APR PY 2015 VL 29 IS 2 BP 355 EP 361 DI 10.1016/j.bpg.2015.02.010 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI8OY UT WOS:000355032800013 PM 25966434 ER PT J AU Lewis, A Irvine, H Ogilvy, C Kimberly, WT AF Lewis, Ariane Irvine, Hannah Ogilvy, Christopher Kimberly, W. Taylor TI Predictors for delayed ventriculoperitoneal shunt placement after external ventricular drain removal in patients with subarachnoid hemorrhage SO BRITISH JOURNAL OF NEUROSURGERY LA English DT Article DE cerebrospinal fluid shunt; CSF dynamics; hydrocephalus; subarachnoid hemorrhage ID NORMAL-PRESSURE HYDROCEPHALUS; DEPENDENT HYDROCEPHALUS; CEREBROSPINAL-FLUID; CEREBRAL ANEURYSMS; REHABILITATION; COILING AB Objective. Hydrocephalus after subarachnoid hemorrhage (SAH) requires temporary cerebrospinal fluid (CSF) drainage using an external ventricular drain (EVD). This drain is removed if patients pass a clamp trial, or a ventriculoperitoneal shunt (VPS) is placed. Little is known about the risk factors for delayed VPS placement in patients who pass a clamp trial and have their EVD removed. In order to explore the risk factors associated with delayed VPS placement, we studied a retrospective cohort of SAH patients at our institution. Methods. We performed a retrospective analysis of SAH patients who had an EVD placed between January 2008 and June 2012 at our institution. We extracted demographic, imaging, and CSF data from the medical record and analyzed risk factors associated with delayed VPS placement. Results. Of 91 patients who passed a clamp trial and had their EVD removed, 12(13%) required delayed VPS placement at a median of 54 (interquartile range: 15-75) days after EVD removal. After multivariate analysis, risk factors for delayed VPS placement included increased CSF protein concentration within the first 7 days of EVD placement (OR: 1.02, CI: 1-1.04, p = 0.023) and increased third ventricular diameter prior to EVD removal (OR: 1.59, CI: 1.11-2.6, p = 0.026). Conclusion. Patients with increased CSF protein concentration at time of EVD placement and those with increased third ventricular diameter at time of EVD removal should be carefully monitored for development of delayed hydrocephalus. C1 [Lewis, Ariane; Irvine, Hannah; Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Ogilvy, Christopher] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Ogilvy, Christopher] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA USA. RP Lewis, A (reprint author), NYU, Langone Med Ctr, 530 First Ave,HCC 5a, New York, NY 10016 USA. EM ariane.kansas.lewis@gmail.com OI Lewis, Ariane/0000-0002-0756-7320 FU Andrew David Heitman Neurovascular Research Foundation FX This work was supported by the Andrew David Heitman Neurovascular Research Foundation (W.T.K. and C.S.O.). The Foundation had no role in study design, collection, analysis, interpretation of data, writing of the manuscript, or decision to submit the manuscript for publication. NR 24 TC 4 Z9 5 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0268-8697 EI 1360-046X J9 BRIT J NEUROSURG JI Br. J. Neurosurg. PD APR PY 2015 VL 29 IS 2 BP 219 EP 224 DI 10.3109/02688697.2014.967753 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CI8LJ UT WOS:000355023500013 PM 25299790 ER PT J AU Oxnard, GR AF Oxnard, Geoffrey R. TI A 78-Year-Old Woman with Brain Metastases Commentary SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM geoffrey_oxnard@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2015 VL 61 IS 4 BP 586 EP 587 DI 10.1373/clinchem.2014.234484 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CJ1SU UT WOS:000355265600006 PM 25818127 ER PT J AU Sundt, TM AF Sundt, Thoralf M. TI With the Best of Intentions SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Editorial Material DE Process measures; Glucose control; Outcomes ID GLYCEMIC CONTROL; CARE C1 Harvard Univ, Sch Med, Dept Surg, Div Cardiac Surg,Massachusetts Gen Hosp,Surg, Boston, MA 02115 USA. RP Sundt, TM (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Cardiac Surg,Massachusetts Gen Hosp,Surg, Boston, MA 02115 USA. EM tsundt@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 EI 1873-734X J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD APR PY 2015 VL 47 IS 4 BP 739 EP 740 DI 10.1093/ejcts/ezu263 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CJ0YP UT WOS:000355207400035 PM 24996407 ER PT J AU Mascitelli, JR Pain, M Panov, F Bederson, JB Patel, AB AF Mascitelli, Justin R. Pain, Margaret Panov, Fedor Bederson, Joshua B. Patel, Aman B. TI Ophthalmic artery occlusion immediately following placement of a flow diverter without clinical sequelae SO INTERVENTIONAL NEURORADIOLOGY LA English DT Article DE Intracranial aneurysm; flow diversion; ophthalmic artery ID PIPELINE EMBOLIZATION DEVICE; INTRACRANIAL ANEURYSMS; ENDOVASCULAR TREATMENT; EXPERIENCE; RECONSTRUCTION AB Branch vessel occlusion is a potential consequence following flow diverter placement for intracranial aneurysms, but the frequency and clinical impact has not been completely elucidated. In this case of a 45-year-old woman with a large left internal carotid artery aneurysm, the ophthalmic artery was covered by two flow diverters and was acutely occluded along with the aneurysm. Common carotid injections failed to demonstrate collateral flow to the ophthalmic artery via the external carotid artery. Nonetheless, the patient woke from anesthesia with objectively stable and subjectively improved vision. This case demonstrates that an acute occlusion of the ophthalmic artery without external carotid artery collaterals can be tolerated clinically. C1 [Mascitelli, Justin R.; Pain, Margaret; Panov, Fedor; Bederson, Joshua B.] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA. [Patel, Aman B.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Patel, Aman B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Patel, AB (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,WAC 745, Boston, MA 02114 USA. EM aman.patel@mountsinai.org NR 14 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1591-0199 EI 2385-2011 J9 INTERV NEURORADIOL JI Interv. Neuroradiol. PD APR PY 2015 VL 21 IS 2 BP 191 EP 195 DI 10.1177/1591019915583217 PG 5 WC Clinical Neurology; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CJ1QS UT WOS:000355259600010 PM 25934658 ER PT J AU de Waard, NE Cao, JF McGuire, SP Kolovou, PE Jordanova, ES Ksander, BR Jager, MJ AF de Waard, Nadine E. Cao, Jinfeng McGuire, Sean P. Kolovou, Paraskevi E. Jordanova, Ekaterina S. Ksander, Bruce R. Jager, Martine J. TI A Murine Model for Metastatic Conjunctival Melanoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE conjunctiva; melanoma; metastatic; mouse model ID HUMAN PROSTATE-CANCER; SKIN CARCINOMA-CELLS; MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; TUMOR PROGRESSION; UVEAL MELANOMA; NRAS MUTATIONS; BRAF MUTATIONS; MOUSE MODELS; ANIMAL-MODEL AB PURPOSE. Conjunctival melanoma (CM) is an ocular malignancy with a high rate of local recurrences after treatment, and can give rise to deadly metastases. The establishment of a murine model will further our understanding of this disease and allow in vivo testing of new therapies. We therefore analyzed the ability of three CM cell lines to grow orthotopically and spread to distant sites. Furthermore, we determined the characteristics of the xenografts and their metastases. METHODS. Orthotopic xenografts of human CM were established by subconjunctival injection of three different CM cell lines into NOD/SCID IL2 r gamma(null) mice. Single-cell suspensions were generated from the primary tumors and placed subconjunctivally in another set of mice, which were then screened for metastases. The presence of melanoma markers was determined on the cell lines and during tumor development. RESULTS. Subconjunctival injection of cultured CM cells into immunodeficient mice led to excellent subconjunctival tumor growth in all inoculated mice (n = 101) within 2 weeks; however, no metastases were found at the time of autopsy. Serial in vivo passage of primary tumor cells resulted in metastatic tumors in the draining lymph nodes (n = 21). The CM cell lines, as well as the tumor xenografts and their metastases, were positive for the melanoma markers HMB-45, S100B, and MART-1. Two cell lines and their corresponding xenografts carried a BRAF mutation, the third showed an NRAS mutation. CONCLUSIONS. We established a murine model for CM that shows excellent formation of metastases in a pattern that accurately resembles metastatic human CM following in vivo passaging. C1 [de Waard, Nadine E.; McGuire, Sean P.; Kolovou, Paraskevi E.; Ksander, Bruce R.; Jager, Martine J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. [de Waard, Nadine E.; Cao, Jinfeng; Jager, Martine J.] Leiden Univ, Med Ctr, Dept Ophthalmol, NL-2300 RC Leiden, Netherlands. [Cao, Jinfeng] Jilin Univ, Hosp 2, Dept Ophthalmol, Changchun 130023, Peoples R China. [Jordanova, Ekaterina S.] Vrije Univ Amsterdam Med Ctr, Dept Obstet & Gynaecol, Ctr Gynaecol Oncol, Amsterdam, Netherlands. RP Jager, MJ (reprint author), Leiden Univ, Med Ctr, Dept Ophthalmol, POB 9600, NL-2300 RC Leiden, Netherlands. EM m.j.jager@lumc.nl OI Jordanova, Ekaterina S./0000-0002-8121-1322 FU Stichting Leids Oogheelkundig Ondersteunings Fonds; Stichting Dondersfonds; Nelly Reef Fund; Alcon BV; Stichting Blindenhulp; China Scholarship Council FX Supported by Stichting Leids Oogheelkundig Ondersteunings Fonds, Stichting Dondersfonds, Nelly Reef Fund, Alcon BV, Stichting Blindenhulp, and China Scholarship Council. NR 44 TC 3 Z9 3 U1 1 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2015 VL 56 IS 4 BP 2325 EP 2333 DI 10.1167/iovs.14-15239 PG 9 WC Ophthalmology SC Ophthalmology GA CJ1NP UT WOS:000355250700023 PM 25722211 ER PT J AU Stock, MV Vollman, DE Baze, EF Chomsky, AS Daly, MK Lawrence, MG AF Stock, Michael V. Vollman, David E. Baze, Elizabeth F. Chomsky, Amy S. Daly, Mary K. Lawrence, Mary G. TI Functional Visual Improvement After Cataract Surgery in Eyes With Age-Related Macular Degeneration: Results of the Ophthalmic Surgical Outcomes Data Project SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cataract surgery; age-related macular degeneration; visual function; visual acuity ID QUALITY-OF-LIFE; IMPACT; POPULATION; ACUITY; PHACOEMULSIFICATION; RISK AB PURPOSE. To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. METHODS. This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We included cases of eyes with AMD that had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes with controls without retinal pathology. We excluded patients with other retinal pathologies (740 patients). The analyses compared changes in visual acuity and overall functional visual improvement and its subscales using t-tests, multivariate logistic regressions, and linear regression modeling. RESULTS. Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of no retinal pathology cases (controls). Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8 +/- 2.4 NEI-VFQ units, P < 0.0001); however, increases were significantly less when compared with controls (-6.4 +/- 2.9 NEI-VFQ units, P < 0.0001). Preoperative best-corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r = -0.38, P < 0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r = -0.075, P = 0.0002). Patients with AMD with vision of 20/40 or better had overall outcomes similar to controls (-2.2 +/- 4.7 NEI-VFQ units, P = 0.37). CONCLUSIONS. Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA of 20/40 or greater, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is less than 20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA. C1 [Stock, Michael V.; Vollman, David E.] VA St Louis Healthcare Syst, St Louis, MO USA. [Stock, Michael V.; Vollman, David E.] Washington Univ, Sch Med, St Louis, MO USA. [Baze, Elizabeth F.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Baze, Elizabeth F.] Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA. [Chomsky, Amy S.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Chomsky, Amy S.] Vanderbilt Univ Med, Vanderbilt Eye Inst, Nashville, TN USA. [Daly, Mary K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Daly, Mary K.] VA Boston Healthcare Syst, Boston, MA USA. [Daly, Mary K.] Harvard Univ, Sch Med, Boston, MA USA. [Lawrence, Mary G.] DoD VA Vis Ctr Excellence, Crystal City, VA USA. RP Stock, MV (reprint author), 660 South Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA. EM stockm@vision.wustl.edu OI Stock, Michael/0000-0001-5404-1105 NR 33 TC 4 Z9 5 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2015 VL 56 IS 4 BP 2536 EP 2540 DI 10.1167/iovs.14-16069 PG 5 WC Ophthalmology SC Ophthalmology GA CJ1NP UT WOS:000355250700050 PM 26066600 ER PT J AU Jeong, SW Patel, N Edlund, CK Hartiala, J Hazelett, DJ Itakura, T Wu, PC Avery, RL Davis, JL Flynn, HW Lalwani, G Puliafito, CA Wafapoor, H Hijikata, M Keicho, N Gao, XY Argueso, P Allayee, H Coetzee, GA Pletcher, MT Conti, DV Schwartz, SG Eaton, AM Fini, ME AF Jeong, Shinwu Patel, Nitin Edlund, Christopher K. Hartiala, Jaana Hazelett, Dennis J. Itakura, Tatsuo Wu, Pei-Chang Avery, Robert L. Davis, Janet L. Flynn, Harry W. Lalwani, Geeta Puliafito, Carmen A. Wafapoor, Hussein Hijikata, Minako Keicho, Naoto Gao, Xiaoyi Argueeso, Pablo Allayee, Hooman Coetzee, Gerhard A. Pletcher, Mathew T. Conti, David V. Schwartz, Stephen G. Eaton, Alexander M. Fini, M. Elizabeth TI Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ocular hypertension; glucocorticoid; GWAS; gene ID GLUCOCORTICOID-RECEPTOR-BETA; OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; TRABECULAR MESHWORK CELLS; INTRAVITREAL TRIAMCINOLONE ACETONIDE; INTRAOCULAR-PRESSURE RESPONSE; RETINAL VEIN OCCLUSION; AQUEOUS-HUMOR OUTFLOW; LONG NONCODING RNAS; EXTRACELLULAR-MATRIX AB PURPOSE. The pathophysiology of ocular hypertension (OH) leading to primary open-angle glaucoma shares many features with a secondary form of OH caused by treatment with glucocorticoids, but also exhibits distinct differences. In this study, a pharmacogenomics approach was taken to discover candidate genes for this disorder. METHODS. A genome-wide association study was performed, followed by an independent candidate gene study, using a cohort enrolled from patients treated with off-label intravitreal triamcinolone, and handling change in IOP as a quantitative trait. RESULTS. An intergenic quantitative trait locus (QTL) was identified at chromosome 6p21.33 near the 5' end of HCG22 that attained the accepted statistical threshold for genome-level significance. The HCG22 transcript, encoding a novel mucin protein, was expressed in trabecular meshwork cells, and expression was stimulated by IL-1, and inhibited by triamcinolone acetate and TGF-beta. Bioinformatic analysis defined the QTL as an approximately 4 kilobase (kb) linkage disequilibrium block containing 10 common single nucleotide polymorphisms (SNPs). Four of these SNPs were identified in the National Center for Biotechnology Information (NCBI) GTEx eQTL browser as modifiers of HCG22 expression. Most are predicted to disrupt or improve motifs for transcription factor binding, the most relevant being disruption of the glucocorticoid receptor binding motif. A second QTL was identified within the predicted signal peptide of the HCG22 encoded protein that could affect its secretion. Translation, O-glycosylation, and secretion of the predicted HCG22 protein was verified in cultured trabecular meshwork cells. CONCLUSIONS. Identification of two independent QTLs that could affect expression of the HCG22 mucin gene product via two different mechanisms (transcription or secretion) is highly suggestive of a role in steroid-induced OH. C1 [Jeong, Shinwu; Patel, Nitin; Hartiala, Jaana; Itakura, Tatsuo; Wu, Pei-Chang; Allayee, Hooman; Fini, M. Elizabeth] Univ So Calif, USC Inst Genet Med, Keck Sch Med USC, Los Angeles, CA 90089 USA. [Jeong, Shinwu; Puliafito, Carmen A.; Fini, M. Elizabeth] Univ So Calif, Dept Ophthalmol, Keck Sch Med USC, USC Eye Inst, Los Angeles, CA 90089 USA. [Edlund, Christopher K.; Allayee, Hooman; Coetzee, Gerhard A.; Conti, David V.] Univ So Calif, Dept Prevent Med, Keck Sch Med USC, Los Angeles, CA 90089 USA. [Hazelett, Dennis J.; Coetzee, Gerhard A.; Fini, M. Elizabeth] Univ So Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med USC, Los Angeles, CA 90089 USA. [Wu, Pei-Chang] Kaohsiung Chang Gung Mem Hosp, Dept Ophthalmol, Kaohsiung, Taiwan. [Avery, Robert L.] Calif Retina Consultants, Santa Barbara, CA USA. [Davis, Janet L.; Flynn, Harry W.; Lalwani, Geeta; Puliafito, Carmen A.; Schwartz, Stephen G.; Fini, M. Elizabeth] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Davis, Janet L.; Flynn, Harry W.; Lalwani, Geeta; Puliafito, Carmen A.; Schwartz, Stephen G.; Fini, M. Elizabeth] Univ Miami, Miller Sch Med, Dept Ophthalmol, Miami, FL 33136 USA. [Puliafito, Carmen A.] Univ So Calif, Keck Sch Med USC, Off Dean, Los Angeles, CA 90089 USA. [Wafapoor, Hussein; Eaton, Alexander M.] Retina Hlth Ctr, Ft Myers, FL USA. [Hijikata, Minako; Keicho, Naoto] Japan AntiTB Assoc, Res Inst TB, Dept Pathophysiol & Host Def, Tokyo, Japan. [Gao, Xiaoyi] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. [Argueeso, Pablo] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Argueeso, Pablo] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med USC, Dept Urol, Los Angeles, CA 90089 USA. [Pletcher, Mathew T.] Scripps Res Inst Scripps Florida, Dept Mol Therapeut, Jupiter, FL USA. [Fini, M. Elizabeth] Univ So Calif, Keck Sch Med USC, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. RP Fini, ME (reprint author), Univ So Calif, USC Inst Genet Med, Hlth Sci Campus,2250 Alcazar St,Suite 240, Los Angeles, CA 90089 USA. EM efini@usc.edu FU National Institutes of Health (NIH; Bethesda, MD, USA) [R01-EY009828, R01-EY022651, R01CA136924, UL1-RR031986, P30-EY014801, P30-CA014089]; Department of Defense [W81XWH-09-1-0675, W81XWH-13-1-0048]; Glaucoma Research Foundation; Research to Prevent Blindness; Prevent Blindness America, Chicago, Illinois, United States; Prevent Blindness Florida, Tampa, Florida, United States; Retina Health Center, Fort Myers, Florida, United States; IC Labs, Fort Myers, Florida, United States; Walter G. Ross Distinguished Chair in Ophthalmic Research at the University of Miami; Keck School of Medicine of USC FX Supported by National Institutes of Health (NIH; Bethesda, MD, USA) Grants R01-EY009828 (MEF), R01-EY022651 (XG), R01CA136924 (GAC), UL1-RR031986 (pilot project subaward, MEF), P30-EY014801 (University of Miami), and P30-CA014089 (NIH/National Cancer Institute, USC); Department of Defense Grants W81XWH-09-1-0675 and W81XWH-13-1-0048 (University of Miami); a Schaffer Innovative Glaucoma Research Grant from the Glaucoma Research Foundation (available in the public domain at http://www.glaucoma.org; MEF); a Senior Scientific Investigator Award from Research to Prevent Blindness (available in the public domain at http://www.rpbusa.org/rpb; MEF); an unrestricted grant from Research to Prevent Blindness (available in the public domain at http://www.rpbusa.org/rpb, University of Miami); an Investigator Award from Prevent Blindness America, Chicago, Illinois, United States (available in the public domain at http://www.preventblindness.org/; SGS); an Investigator Award from Prevent Blindness Florida, Tampa, Florida, United States (available in the public domain at http://florida.preventblindness.org/; SGS); the Retina Health Center, Fort Myers, Florida, United States (available in the public domain at http://www.retinahealthcenter.com/; to support research staff involved in sample and data acquisition, AME); IC Labs, Fort Myers, Florida, United States (costs of the Illumina chip screening in the USC Epigenomics Center Core Facility, AME); Walter G. Ross Distinguished Chair in Ophthalmic Research at the University of Miami (MEF); and the Keck School of Medicine of USC (start-up funding for MEF). NR 115 TC 8 Z9 8 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2015 VL 56 IS 4 BP 2737 EP 2748 DI 10.1167/iovs.14-14803 PG 12 WC Ophthalmology SC Ophthalmology GA CJ1NP UT WOS:000355250700075 PM 25813999 ER PT J AU Hwang, TJ Ciolino, JB AF Hwang, Thomas J. Ciolino, Joseph B. TI Retinal Implants and Medicare Reimbursement Policies for Breakthrough Treatments in Ophthalmology SO JAMA OPHTHALMOLOGY LA English DT Editorial Material C1 [Hwang, Thomas J.] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. [Hwang, Thomas J.] Blackstone Grp, London W1J 5AL, England. [Ciolino, Joseph B.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Ciolino, Joseph B.] Harvard Univ, Sch Med, Boston, MA USA. RP Hwang, TJ (reprint author), Blackstone Grp, 40 Berkeley Sq, London W1J 5AL, England. EM tjhwang@post.harvard.edu FU NEI NIH HHS [1K08EY019686-01] NR 7 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD APR PY 2015 VL 133 IS 4 BP 373 EP 374 DI 10.1001/jamaophthalmol.2015.54 PG 2 WC Ophthalmology SC Ophthalmology GA CI8CK UT WOS:000354995100011 PM 25675029 ER PT J AU Scarcelli, G Besner, S Pineda, R Kalout, P Yun, SH AF Scarcelli, Giuliano Besner, Sebastien Pineda, Roberto Kalout, Patricia Yun, Seok Hyun TI In Vivo Biomechanical Mapping of Normal and Keratoconus Corneas SO JAMA OPHTHALMOLOGY LA English DT Letter ID MICROSCOPY C1 [Scarcelli, Giuliano; Besner, Sebastien; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Scarcelli, Giuliano; Besner, Sebastien; Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Pineda, Roberto; Kalout, Patricia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Yun, SH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. EM syun@mgh.harvard.edu FU NCRR NIH HHS [UL1 RR025758, UL1-RR025758]; NEI NIH HHS [R01 EY025454, R21 EY023043, R21EY023043]; NIBIB NIH HHS [K25 EB015885, K25EB015885, P41 EB015903] NR 6 TC 10 Z9 10 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD APR PY 2015 VL 133 IS 4 BP 480 EP 482 DI 10.1001/jamaophthalmol.2014.5641 PG 4 WC Ophthalmology SC Ophthalmology GA CI8CK UT WOS:000354995100031 PM 25611213 ER PT J AU Beidas, RS Marcus, S Aarons, GA Hoagwood, KE Schoenwald, S Evans, AC Hurford, MO Hadley, T Barg, FK Walsh, LM Adams, DR Mandell, DS AF Beidas, Rinad S. Marcus, Steven Aarons, Gregory A. Hoagwood, Kimberly E. Schoenwald, Sonja Evans, Arthur C. Hurford, Matthew O. Hadley, Trevor Barg, Frances K. Walsh, Lucia M. Adams, Danielle R. Mandell, David S. TI Predictors of Community Therapists' Use of Therapy Techniques in a Large Public Mental Health System SO JAMA PEDIATRICS LA English DT Article ID ORGANIZATIONAL SOCIAL-CONTEXT; CHILDRENS SERVICE SYSTEMS; TREATMENT FIDELITY; WELFARE SYSTEMS; FAMILY-THERAPY; IMPLEMENTATION; ATTITUDES; CLIMATE; OUTCOMES; YOUTH AB IMPORTANCE Few studies have examined the effects of individual and organizational characteristics on the use of evidence-based practices in mental health care. Improved understanding of these factors could guide future implementation efforts to ensure effective adoption, implementation, and sustainment of evidence-based practices. OBJECTIVE To estimate the relative contribution of individual and organizational factors on therapist self-reported use of cognitive-behavioral, family, and psychodynamic therapy techniques within the context of a large-scale effort to increase use of evidence-based practices in an urban public mental health system serving youth and families. DESIGN, SETTING, AND PARTICIPANTS In this observational, cross-sectional study of 23 organizations, data were collected from March 1 through July 25, 2013. We used purposive sampling to recruit the 29 largest child-serving agencies, which together serve approximately 80% of youth receiving publically funded mental health care. The final sample included 19 agencies with 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators. MAIN OUTCOMES AND MEASURES Therapist self-reported use of cognitive-behavioral, family, and psychodynamic therapy techniques, as measured by the Therapist Procedures Checklist-Family Revised. RESULTS Individual factors accounted for the following percentages of the overall variation: cognitive-behavioral therapy techniques, 16%; family therapy techniques, 7%; and psychodynamic therapy techniques, 20%. Organizational factors accounted for the following percentages of the overall variation: cognitive-behavioral therapy techniques, 23%; family therapy techniques, 19%; and psychodynamic therapy techniques, 7%. Older therapists and therapists with more open attitudes were more likely to endorse use of cognitive-behavioral therapy techniques, as were those in organizations that had spent fewer years participating in evidence-based practice initiatives, had more resistant cultures, and had more functional climates. Women were more likely to endorse use of family therapy techniques, as were those in organizations employing more fee-for-service staff and with more stressful climates. Therapists with more divergent attitudes and less knowledge about evidence-based practices were more likely to use psychodynamic therapy techniques. CONCLUSIONS AND RELEVANCE This study suggests that individual and organizational factors are important in explaining therapist behavior and use of evidence-based practices, but the relative importance varies by therapeutic technique. C1 [Beidas, Rinad S.; Evans, Arthur C.; Hurford, Matthew O.; Hadley, Trevor; Walsh, Lucia M.; Adams, Danielle R.; Mandell, David S.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Marcus, Steven] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Marcus, Steven] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Aarons, Gregory A.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Hoagwood, Kimberly E.] NYU, Dept Psychiat, New York, NY 10016 USA. [Schoenwald, Sonja] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Evans, Arthur C.; Hurford, Matthew O.] Dept Behav Hlth & Intellectual Disabil Serv, Philadelphia, PA USA. [Hurford, Matthew O.] Community Behav Hlth, Philadelphia, PA USA. [Barg, Frances K.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. RP Beidas, RS (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, 3535 Market St,3015, Philadelphia, PA 19104 USA. EM rbeidas@upenn.edu RI Mandell, David/H-2730-2012 OI Mandell, David/0000-0001-8240-820X FU Implementation Research Institute fellowship from the National Institute of Mental Health [K23 MH099179]; Implementation Research Institute, George Warren Brown School of Social Work, Washington University, St Louis, Missouri; National Institute of Mental Health [R25 MH080916]; Quality Enhancement Research Initiative, Department of Veterans Affairs Contract, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service FX This study was supported by grant K23 MH099179 and an Implementation Research Institute fellowship (2012-2014) from the National Institute of Mental Health (Dr Beidas); the Implementation Research Institute, George Warren Brown School of Social Work, Washington University, St Louis, Missouri; grant R25 MH080916 from the National Institute of Mental Health; and the Quality Enhancement Research Initiative, Department of Veterans Affairs Contract, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service. NR 38 TC 19 Z9 19 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD APR PY 2015 VL 169 IS 4 BP 374 EP 382 DI 10.1001/jamapediatrics.2014.3736 PG 9 WC Pediatrics SC Pediatrics GA CI8CP UT WOS:000354995600021 PM 25686473 ER PT J AU Ager, EI Kozin, SV Kirkpatrick, ND Seano, G Kodack, DP Askoxylakis, V Huang, YH Goel, S Snuderl, M Muzikansky, A Finkelstein, DM Dransfield, DT Devy, L Boucher, Y Fukumura, D Jain, RK AF Ager, Eleanor I. Kozin, Sergey V. Kirkpatrick, Nathaniel D. Seano, Giorgio Kodack, David P. Askoxylakis, Vasileios Huang, Yuhui Goel, Shom Snuderl, Matija Muzikansky, Alona Finkelstein, Dianne M. Dransfield, Daniel T. Devy, Laetitia Boucher, Yves Fukumura, Dai Jain, Rakesh K. TI Blockade of MMP14 Activity in Murine Breast Carcinomas: Implications for Macrophages, Vessels, and Radiotherapy SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MATRIX-METALLOPROTEINASE INHIBITORS; NITRIC-OXIDE SYNTHASE; TGF-BETA; CANCER CELLS; VASCULAR NORMALIZATION; TUMOR MICROENVIRONMENT; DRUG-DELIVERY; IN-VIVO; ANGIOGENESIS; THERAPY AB Background: Matrix metalloproteinase (MMP) 14 may mediate tumor progression through vascular and immune-modulatory effects. Methods: Orthotopic murine breast tumors (4T1 and E0771 with high and low MMP14 expression, respectively; n = 5-10 per group) were treated with an anti-MMP14 inhibitory antibody (DX-2400), IgG control, fractionated radiation therapy, or their combination. We assessed primary tumor growth, transforming growth factor beta (TGF beta) and inducible nitric oxide synthase (iNOS) expression, macrophage phenotype, and vascular parameters. A linear mixed model with repeated observations, with Mann-Whitney or analysis of variance with Bonferroni post hoc adjustment, was used to determine statistical significance. All statistical tests were two-sided. Results: DX-2400 inhibited tumor growth compared with IgG control treatment, increased macrophage numbers, and shifted the macrophage phenotype towards antitumor M1-like. These effects were associated with a reduction in active TGF beta and SMAD2/3 signaling. DX-2400 also transiently increased iNOS expression and tumor perfusion, reduced tissue hypoxia (median % area: control, 20.2%, interquartile range (IQR) = 6.4%-38.9%; DX-2400: 1.2%, IQR = 0.2%-3.2%, P = .044), and synergistically enhanced radiation therapy (days to grow to 800 mm(3): control, 12 days, IQR = 9-13 days; DX-2400 plus radiation, 29 days, IQR = 26-30 days, P < .001) in the 4T1 model. The selective iNOS inhibitor, 1400W, abolished the effects of DX-2400 on vessel perfusion and radiotherapy. On the other hand, DX-2400 was not capable of inducing iNOS expression or synergizing with radiation in E0771 tumors. Conclusion: MMP14 blockade decreased immunosuppressive TGF beta, polarized macrophages to an antitumor phenotype, increased iNOS, and improved tumor perfusion, resulting in reduced primary tumor growth and enhanced response to radiation therapy, especially in high MMP14-expressing tumors. C1 [Ager, Eleanor I.; Kozin, Sergey V.; Kirkpatrick, Nathaniel D.; Seano, Giorgio; Kodack, David P.; Askoxylakis, Vasileios; Huang, Yuhui; Goel, Shom; Snuderl, Matija; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. [Ager, Eleanor I.; Kozin, Sergey V.; Kirkpatrick, Nathaniel D.; Seano, Giorgio; Kodack, David P.; Askoxylakis, Vasileios; Huang, Yuhui; Goel, Shom; Snuderl, Matija; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Ager, Eleanor I.] Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic, Australia. [Ager, Eleanor I.] Novogen, Hornsby, NSW, Australia. [Kirkpatrick, Nathaniel D.] Novartis Inst BioMed Res, Cambridge, MA USA. [Goel, Shom] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Camperdown, NSW, Australia. [Muzikansky, Alona; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Dept Biostat, Ctr Biostat, Boston, MA 02114 USA. [Snuderl, Matija] NYU Langone Med Ctr, Dept Pathol, New York, NY USA. [Snuderl, Matija] Sch Med, New York, NY USA. [Dransfield, Daniel T.; Devy, Laetitia] Dyax Corp, Burlington, MA USA. [Goel, Shom] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Goel, Shom] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Dransfield, Daniel T.] Tokai Pharmaceut Inc, Cambridge, MA USA. [Devy, Laetitia] Merck Serono SA, Geneva, Switzerland. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu RI Seano, Giorgio/R-6611-2016; OI Seano, Giorgio/0000-0002-7294-302X; Ager, Eleanor/0000-0002-7849-9206; Huang, Yuhui/0000-0003-1985-3575; Snuderl, Matija/0000-0003-0752-0917 NR 47 TC 13 Z9 14 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv017 DI 10.1093/jnci/djv017 PG 12 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500016 ER PT J AU Schully, SD Carrick, DM Mechanic, LE Srivastava, S Anderson, GL Baron, JA Berg, CD Cullen, J Diamandis, EP Doria-Rose, VP Goddard, KAB Hankinson, SE Kushi, LH Larson, EB McShane, LM Schilsky, RL Shak, S Skates, SJ Urban, N Kramer, BS Khoury, MJ Ransohoff, DF AF Schully, Sheri D. Carrick, Danielle M. Mechanic, Leah E. Srivastava, Sudhir Anderson, Garnet L. Baron, John A. Berg, Christine D. Cullen, Jennifer Diamandis, Eleftherios P. Doria-Rose, V. Paul Goddard, Katrina A. B. Hankinson, Susan E. Kushi, Lawrence H. Larson, Eric B. McShane, Lisa M. Schilsky, Richard L. Shak, Steven Skates, Steven J. Urban, Nicole Kramer, Barnett S. Khoury, Muin J. Ransohoff, David F. TI Leveraging Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID OVARIAN-CANCER; ALGORITHM ROCA; BIOMARKER; RISK; SPECIMENS; ACCURACY; OPINION; DESIGN; MODELS; LUNG AB Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. C1 [Schully, Sheri D.; Carrick, Danielle M.; Mechanic, Leah E.; Doria-Rose, V. Paul; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Srivastava, Sudhir; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [McShane, Lisa M.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Anderson, Garnet L.; Urban, Nicole] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Baron, John A.; Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Berg, Christine D.] Johns Hopkins Med, Dept Radiat Oncol, Baltimore, MD USA. [Cullen, Jennifer] Ctr Prostate Dis Res, Dept Def, Rockville, MD USA. [Diamandis, Eleftherios P.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Goddard, Katrina A. B.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Kushi, Lawrence H.] Kaiser Permanente, Div Res, Oakland, CA USA. [Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA USA. [Shak, Steven] Genom Hlth Inc, Redwood City, CA USA. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Gen, Atlanta, GA USA. RP Schully, SD (reprint author), 9609 Med Ctr Dr 4E106, Rockville, MD 20850 USA. EM schullys@mail.nih.gov OI Doria-Rose, Vincent/0000-0002-8802-5143 NR 31 TC 7 Z9 7 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv012 DI 10.1093/jnci/djv012 PG 7 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500014 ER PT J AU Song, MY Nishihara, R Wu, KN Qian, ZR Kim, SA Sukawa, Y Mima, K Inamura, K Masuda, A Yang, JH Fuchs, CS Giovannucci, EL Ogino, S Chan, AT AF Song, Mingyang Nishihara, Reiko Wu, Kana Qian, Zhi Rong Kim, Sun A. Sukawa, Yasutaka Mima, Kosuke Inamura, Kentaro Masuda, Atsuhiro Yang, Juhong Fuchs, Charles S. Giovannucci, Edward L. Ogino, Shuji Chan, Andrew T. TI Marine omega-3 Polyunsaturated Fatty Acids and Risk for Colorectal Cancer According to Microsatellite Instability SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DNA MISMATCH REPAIR; FOOD FREQUENCY QUESTIONNAIRE; DIETARY-INTAKE; MOLECULAR-FEATURES; ULCERATIVE-COLITIS; CELL-PROLIFERATION; WOMEN; INFLAMMATION; N-3; MEN AB Background: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine omega-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive. Methods: We investigated whether the association between marine omega-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses' Health Study and Health Professionals Follow-up Study. We documented and classified 1125 CRC cases into either MSI-high tumors, in which 30% or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine omega-3 PUFA intake. All statistical tests were two-sided. Results: Marine omega-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P-heterogeneity = .02): High marine omega-3 PUFA intake was associated with a lower risk for MSI-high tumors (comparing >= 0.30g/d with <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P-linearity = .03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P-linearity = .28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status. Conclusions: High marine omega-3 PUFA intake is associated with lower risk for MSI-high CRC but not MSS tumors, suggesting a potential role of omega-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms. C1 [Song, Mingyang; Nishihara, Reiko; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Nishihara, Reiko; Qian, Zhi Rong; Kim, Sun A.; Sukawa, Yasutaka; Mima, Kosuke; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko; Qian, Zhi Rong; Kim, Sun A.; Sukawa, Yasutaka; Mima, Kosuke; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Inamura, Kentaro] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Channing Div Network Med, Dept Med,Brigham & Womens Hosp, Boston, MA 02215 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu; achan@partners.org RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU National Institutes of Health [P01 CA87969, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, K24 DK 098311, K07 CA190673, 1U54CA155626]; Agrusa Fund for Colorectal Cancer Research FX This work was supported by the National Institutes of Health (P01 CA87969, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, K24 DK 098311, K07 CA190673, and 1U54CA155626) and by a grant from the Agrusa Fund for Colorectal Cancer Research. NR 56 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv007 DI 10.1093/jnci/djv007 PG 8 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500010 ER PT J AU Henry, FP Wang, Y Rodriguez, CLR Randolph, MA Rust, EAZ Winograd, JM de Boer, JF Park, BH AF Henry, Francis P. Wang, Yan Rodriguez, Carissa L. R. Randolph, Mark A. Rust, Esther A. Z. Winograd, Jonathan M. de Boer, Johannes F. Park, B. Hyle TI In vivo optical microscopy of peripheral nerve myelination with polarization sensitive-optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE polarization sensitive-optical coherence tomography; myelin; sciatic function index ID FIBER LAYER THICKNESS; SCIATIC-NERVE; SPECTRAL INTERFEROMETRY; CRUSH INJURIES; DYNAMIC-RANGE; DEMYELINATION; TISSUES; RADAR; EYES; SKIN AB Assessing nerve integrity and myelination after injury is necessary to provide insight for treatment strategies aimed at restoring neuromuscular function. Currently, this is largely done with electrical analysis, which lacks direct quantitative information. In vivo optical imaging with sufficient imaging depth and resolution could be used to assess the nerve microarchitecture. In this study, we examine the use of polarization sensitive-optical coherence tomography (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through measurements of birefringence after applying a nerve crush injury in a rat model. Initial loss of function and subsequent recovery were demonstrated by calculating the sciatic function index (SFI). We found that the PS-OCT phase retardation slope, which is proportional to birefringence, increased monotonically with the SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio shows that the PS-OCT slope is a good indicator of myelin health and recovery after injury. These results demonstrate that PS-OCT is capable of providing nondestructive and quantitative assessment of nerve health after injury and shows promise for continued use both clinically and experimentally in neuroscience. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Henry, Francis P.; Wang, Yan; de Boer, Johannes F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Henry, Francis P.; Randolph, Mark A.; Rust, Esther A. Z.; Winograd, Jonathan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. [Wang, Yan; Rodriguez, Carissa L. R.; Park, B. Hyle] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA. [de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM marandolph@partners.org; hylepark@engr.ucr.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU Department of Defense, Medical Free Electron Laser Program [FA9550-04-1-0079]; Center for Integration of Medicine and Innovative Technology (CIMIT) [2007A003268]; National Institutes of Health [R01-019768, K99/R00-EB007241]; Bullock-Wellman Fellowship; Wellman Center for Photomedicine; Health, Science and Technology Division (HST) of Harvard Medical School; National Science Foundation IGERT Fellowship [DGE 00903667] FX The authors gratefully acknowledge the support from the Department of Defense, Medical Free Electron Laser Program FA9550-04-1-0079 and The Center for Integration of Medicine and Innovative Technology (CIMIT) grant 2007A003268. Technology development was supported in part by the National Institutes of Health under grant R01-019768. Dr. Henry gratefully acknowledges support from the Bullock-Wellman Fellowship, awarded by the Wellman Center for Photomedicine and The Health, Science and Technology Division (HST) of Harvard Medical School. Dr. Park gratefully acknowledges support from the National Institutes of Health under grant K99/R00-EB007241. Carissa Rodriguez gratefully acknowledges the support from the National Science Foundation IGERT Fellowship DGE 00903667. The authors gratefully acknowledge the assistance of Ms. Peggy Sherwood for histological processing, David Zurakowski, PhD, for statistical analysis, and Christopher L. Passaglia, PhD, for critical review of the manuscript. NR 45 TC 4 Z9 4 U1 2 U2 8 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2015 VL 20 IS 4 AR 046002 DI 10.1117/1.JBO.20.4.046002 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CJ1ZD UT WOS:000355282800011 PM 25858593 ER PT J AU Mallidi, S Mai, ZM Rizvi, I Hempstead, J Arnason, S Celli, J Hasan, T AF Mallidi, Srivalleesha Mai, Zhiming Rizvi, Imran Hempstead, Joshua Arnason, Stephen Celli, Jonathan Hasan, Tayyaba TI In vivo evaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article ID TOPICAL 5-AMINOLEVULINIC ACID; FLUENCE RATE; CELL CARCINOMA; CANCER; HYPOXIA; PDT; MODEL; CAIX; FRACTIONATION; SMARTPHONE AB In view of the increase in cancer-related mortality rates in low-to middle-income countries (LMIC), there is an urgent need to develop economical therapies that can be utilized at minimal infrastructure institutions. Photodynamic therapy (PDT), a photochemistry-based treatment modality, offers such a possibility provided that low-cost light sources and photosensitizers are available. In this proof-of-principle study, we focus on adapting the PDT light source to a low-resource setting and compare an inexpensive, portable, battery-powered light-emitting diode (LED) light source with a standard, high-cost laser source. The comparison studies were performed in vivo in a xenograft murine model of human squamous cell carcinoma subjected to 5-aminolevulinic acid-induced protoporphyrin IX PDT. We observed virtually identical control of the tumor burden by both the LED source and the standard laser source. Further insights into the biological response were evaluated by biomarker analysis of necrosis, microvessel density, and hypoxia [carbonic anhydrase IX (CAIX) expression] among groups of control, LED-PDT, and laser-PDT treated mice. There is no significant difference in the percent necrotic volume and CAIX expression in tumors that were treated with the two different light sources. These encouraging preliminary results merit further investigations in orthotopic animal models of cancers prevalent in LMICs. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. C1 [Mallidi, Srivalleesha; Mai, Zhiming; Rizvi, Imran; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rizvi, Imran] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hempstead, Joshua; Arnason, Stephen; Celli, Jonathan] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu RI Emchi, Karma/Q-1952-2016 FU NIH [F32CA165881, 1K99CA175292, R00CA155045, UH2CA189901, 5P01CA084203] FX This work was supported by NIH grants F32CA165881 (Mallidi), 1K99CA175292 (Rizvi), R00CA155045 (Celli), UH2CA189901 (Hasan and Celli) and 5P01CA084203 (Hasan). The authors thank Dr. Jie Zhao and Mrs. Winxing Lin at the Wellman Center Photopathology core for cryo-cutting the samples. We also thank Dr. Rehab Amin for assisting the authors with immunofluorescence stains, Dustin P. Jones, Abdelali Ziouche and Gwendolyn Cramer at University of Massachusetts Boston for fabrication and characterization of the LED light source and Zachary Simpson at Wellman Center for assistance with editing. NR 48 TC 1 Z9 1 U1 1 U2 10 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2015 VL 20 IS 4 AR 048003 DI 10.1117/1.JBO.20.4.048003 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CJ1ZD UT WOS:000355282800032 PM 25909707 ER PT J AU Cohen, BE Shi, Y Neylan, TC Maguen, S Seal, KH AF Cohen, Beth E. Shi, Ying Neylan, Thomas C. Maguen, Shira Seal, Karen H. TI Antipsychotic Prescriptions in Iraq and Afghanistan Veterans With Posttraumatic Stress Disorder in Department of Veterans Affairs Healthcare, 2007-2012 SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CARDIOVASCULAR RISK; DIAGNOSES; TRENDS; PTSD; METAANALYSIS; RISPERIDONE AB Objective: Antipsychotic medications have been increasingly prescribed for off-label uses, including treatment of posttraumatic stress disorder (PTSD). Given limited knowledge about their use in returning Iraq and Afghanistan veterans with PTSD, we explored rates of antipsychotic use in this population and correlations with sociodemographic, military service, and psychiatric factors. Method: Iraq and Afghanistan veterans with a PTSD diagnosis based on ICD-9-CM codes enrolled in Veterans Administration care between January 1, 2007, and September 30, 2011, were followed through September 30, 2012. Patients with a comorbid diagnosis of schizophrenia or bipolar disorder were excluded. Poisson regression models evaluated factors associated with prescriptions for antipsychotic versus other psychiatric medications (primary outcome). Results: The mean age of our study population was 29.3 years, and 9.4% were women. Of 186,460 veterans with PTSD diagnoses examined, 19.9% received no psychiatric medications, and the remainder received psychiatric medications that excluded (61.2%) or included (18.9%) antipsychotics. In adjusted models, several factors were independently associated with antipsychotic use, including male sex (adjusted relative risk = 1.25; 95% CI, 1.20-1.30) and enlisted rank (1.44; 95% CI, 1.35-1.53). Increased likelihood of antipsychotic prescribing was associated with suicidal ideation (4.77; 95% CI, 4.59-4.95) and comorbid psychiatric diagnoses including personality disorder (4.27; 95% CI, 4.09-4.46), drug use disorder (3.56; 95% CI, 3.43-3.69), and alcohol use disorder (2.75; 95% CI, 2.65-2.84). Conclusions: A substantial minority of Iraq and Afghanistan veterans diagnosed with PTSD received antipsychotics. Male veterans, those of enlisted rank, and those with suicidal ideation and psychiatric comorbidities were more likely to receive antipsychotics than other types of psychiatric medications. Providers should be cautious about antipsychotic use, given their known metabolic risks and questionable benefits for PTSD. C1 [Cohen, Beth E.; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Neylan, Thomas C.; Maguen, Shira; Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth E.; Shi, Ying; Neylan, Thomas C.; Maguen, Shira; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Cohen, BE (reprint author), San Francisco VA Med Ctr, Box 111A1,4150 Clement St, San Francisco, CA 94120 USA. EM Beth.Cohen@va.gov FU National Heart, Lung, and Blood Institute grant [K23 HL 094765-01]; American Heart Association Clinical Research Program; VA Health Services Research and Development Research Enhancement Award Program at San Francisco VA Medical Center FX Dr Cohen was supported by National Heart, Lung, and Blood Institute grant K23 HL 094765-01 and a grant from the American Heart Association Clinical Research Program. This work was also supported by the VA Health Services Research and Development Research Enhancement Award Program at the San Francisco VA Medical Center. NR 26 TC 1 Z9 1 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2015 VL 76 IS 4 BP 406 EP + DI 10.4088/JCP.13m08857 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CI8DA UT WOS:000354997500021 PM 25845036 ER PT J AU Papakostas, GI Ostergaard, SD Iovieno, N AF Papakostas, George I. Ostergaard, Soren D. Iovieno, Nadia TI The Nature of Placebo Response in Clinical Studies of Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID LATE-LIFE DEPRESSION; CONTROLLED RANDOMIZED-TRIALS; STAR-ASTERISK-D; ANTIDEPRESSANT EFFICACY TRIALS; WHITE-MATTER HYPERINTENSITIES; PATIENT-LEVEL METAANALYSIS; FOLLOW-UP ASSESSMENTS; HAMILTON RATING-SCALE; DOUBLE-BLIND; META-REGRESSION AB Objective: To review factors influencing placebo response and clinical trial outcome in depression, and suggest ways to optimize trial success in mood disorders. Data Sources: PubMed searches were conducted by cross-referencing the terms depression, depressive with placebo, clinical trial, and clinical trials for studies published in English between 1970 and September 2013. Study Selection: Relevant abstracts were identified in PubMed, including clinical trials, quantitative studies, and qualitative research. We obtained and reviewed relevant articles and utilized their information to synthesize the present review. Data Extraction: Included articles were grouped in the following areas of relevance: (1) biological validity of illness, (2) baseline severity of illness, (3) chronicity of the index episode of depression, (4) age of participants, (5) medical and psychiatric comorbidity, (6) probability of receiving placebo, (7) use of prospective treatment phases (leadin) (8) dosing schedule, (9) trial duration, (10) frequency of follow-up assessments, and (11) study outcome measure. Results: Several key elements emerge as critical to the ultimate success of a clinical trial, including the probability of receiving placebo, study duration, dosing schedule, visit frequency, the use of blinded lead-in phases, the use of centralized raters, illness severity and duration, and comorbid anxiety. Conclusions: Our increasing understanding of the placebo response in clinical trials of major depressive disorder lends to a, gradually, more predictable phenomenon and, hopefully, to one that becomes lesser in magnitude and variability. Several elements have emerged that seem to play a critical role in trial success, gradually reshaping the design of clinical, translational, as well as mechanistic studies in depression. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Papakostas, George I.; Iovieno, Nadia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Ostergaard, Soren D.] Aarhus Univ Hosp Risskov, Res Dept P, Risskov, Denmark. [Ostergaard, Soren D.] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Trials Network & Inst, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM gpapakostas@partners.org OI Ostergaard, Soren Dinesen/0000-0002-8032-6208 FU AstraZeneca PLC; Bristol-Myers Squibb; Forest; National Institute of Mental Health; PAMLAB; Ridge Diagnostics; Sunovion; Theracos FX Dr Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca PLC, Avanir, Brainsway, Bristol-Myers Squibb, Cephalon, Dey Pharma LP, Eli Lilly, Genentech, GlaxoSmithKline, Evotec AG, H. Lundbeck A/S, Inflabloc, Jazz, Novartis AG, Otsuka, PAMLAB, Pfizer, Pierre Fabre, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire, Sunovion, Takeda, Theracos, and Wyeth; has received honoraria from Abbott Laboratories, AstraZeneca PLC, Avanir, Bristol-Myers Squibb, Brainsway, Cephalon, Dey Pharma LP, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc, Jazz, H. Lundbeck A/S, Meiji Seika, Novartis Pharma AG, Otsuka, PAMLAB, Pfizer, Pierre Fabre, Ridge Diagnostics, Shire, Sunovion, Takeda, Theracos, Titan, and Wyeth; has received research support from AstraZeneca PLC, Bristol-Myers Squibb, Forest, National Institute of Mental Health, PAMLAB, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion, and Theracos; and has served (not currently) on the speaker's bureau for Bristol-Myers Squibb and Pfizer. Drs Iovieno and Ostergaard report no financial or other relationship relevant to the subject of this article. NR 89 TC 17 Z9 19 U1 4 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2015 VL 76 IS 4 BP 456 EP 466 DI 10.4088/JCP.14r09297 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CI8DA UT WOS:000354997500027 PM 25919832 ER PT J AU Gabrielian, S Bromley, E Hellemann, GS Kern, RS Goldenson, NI Danley, ME Young, AS AF Gabrielian, Sonya Bromley, Elizabeth Hellemann, Gerhard S. Kern, Robert S. Goldenson, Nicholas I. Danley, Megan E. Young, Alexander S. TI Factors Affecting Exits From Homelessness Among Persons With Serious Mental Illness and Substance Use Disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COGNITIVE ASSESSMENT-TOOL; QUALITY-OF-LIFE; SOCIAL SUPPORT; SCREENING-TEST; VOCATIONAL-REHABILITATION; PSYCHOMETRIC PROPERTIES; COMMUNITY INTEGRATION; OLDER-ADULTS; SCHIZOPHRENIA; HEALTH AB Objective: We sought to understand the housing trajectories of homeless consumers with serious mental illness (SMI) and co-occurring substance use disorders (SUD) and to identify factors that best predicted achievement of independent housing. Method: Using administrative data, we identified homeless persons with SMI and SUD admitted to a residential rehabilitation program from December 2008 to November 2011. Our primary outcome measure was independent housing status. On a random sample (N = 36), we assessed a range of potential predictors of housing outcomes, including symptoms, cognition, and social/community supports. We used the Residential Time-Line Follow-Back (TLFB) Inventory to gather housing histories since exiting rehabilitation and to identify housing outcomes. We used Recursive Partitioning (RP) to identify variables that best differentiated participants by these outcomes. Results: We identified 3 housing trajectories: stable housing (n = 14), unstable housing (n = 15), and continuously engaged in housing services (n = 7). In RP analysis, 2 variables (Symbol Digit Modalities Test [SDMT], a neurocognitive speed of processing measure, and Behavior and Symptom Identification Scale [BASIS-24] Relationships subscale, which quantifies symptoms affecting relationships) were sufficient to capture information provided by 26 predictors to classify participants by housing outcome. Participants predicted to continuously engage in services had impaired processing speeds (SDMT score < 32.5). Among consumers with SDMT score = 32.5, those predicted to achieve stable housing had fewer interpersonal symptoms (BASIS-24 Relationships subscale score < 0.81) than those predicted to have unstable housing. This model explains 57% of this sample's variability and 14% of this population's variability in housing outcomes. Conclusions: Because cognition and symptoms influencing relationships predicted housing outcomes for homeless adults with SMI and SUD, cognitive and social skills training may be useful for this population. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Gabrielian, Sonya; Bromley, Elizabeth; Young, Alexander S.] Greater Los Angeles Healthcare Syst, US Dept Vet Affairs, Dept Psychiat, Los Angeles, CA 90073 USA. [Gabrielian, Sonya; Bromley, Elizabeth; Hellemann, Gerhard S.; Kern, Robert S.; Young, Alexander S.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Gabrielian, Sonya; Bromley, Elizabeth; Kern, Robert S.; Young, Alexander S.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Vet Affairs VISN22, MIRECC, Los Angeles, CA USA. [Gabrielian, Sonya; Bromley, Elizabeth; Hellemann, Gerhard S.; Young, Alexander S.] VA Ctr Study Healthcare Innovat Implementat & Pol, North Hills, CA USA. [Goldenson, Nicholas I.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Danley, Megan E.] Univ Calif San Francisco, Sch Med, Dept Phys Therapy & Rehabil Sci, San Francisco, CA USA. RP Gabrielian, S (reprint author), Greater Los Angeles Healthcare Syst, US Dept Vet Affairs, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. EM sonya.gabrielian@va.gov FU Department of Veterans Affairs VISN22 MIRECC Pala Grant (Los Angeles, California); VA Center for the Study of Healthcare Innovation, Implementation, and Policy (North Hills, California); Veterans Health Administration, Office of Research and Development, Health Services Research and Development (Washington, DC) [RRP 12-259]; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, US Department of Veterans Affairs FX This material is based upon work supported by a Department of Veterans Affairs VISN22 MIRECC Pala Grant (Los Angeles, California); Locally Initiated Project funds from the VA Center for the Study of Healthcare Innovation, Implementation, and Policy (North Hills, California); and the Veterans Health Administration, Office of Research and Development, Health Services Research and Development, RRP 12-259 (Washington, DC). Dr Gabrielian was supported in part by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, US Department of Veterans Affairs. NR 61 TC 1 Z9 1 U1 0 U2 18 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2015 VL 76 IS 4 BP E469 EP E476 DI 10.4088/JCP.14m09229 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CI8DA UT WOS:000354997500001 PM 25919839 ER PT J AU Nierenberg, AA Sylvia, L Doederlein, A Edgman-Levitan, S Muskin, A Jewell, L Walker, M Goodman, D Farahbakhsh, M Hearing, C Tovey, R Deckersbach, T AF Nierenberg, Andrew A. Sylvia, Louisa Doederlein, Allen Edgman-Levitan, Susan Muskin, Alies Jewell, Lucinda Walker, Muffy Goodman, Dan Farahbakhsh, Massoud Hearing, Casey Tovey, Roberta Deckersbach, Thilo TI Improving the Care of Patients Who Have Treatment-Resistant Depression: The Promise of the PCORnet Mood Network SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID STAR-ASTERISK-D; BIPOLAR DISORDER; CLINICAL-PRACTICE; DESIGN; RATIONALE; TRIALS; MEDICATIONS; OUTCOMES; LITMUS C1 [Nierenberg, Andrew A.; Sylvia, Louisa; Hearing, Casey; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Goodman, Dan; Farahbakhsh, Massoud; Tovey, Roberta] Massachusetts Gen Hosp, MoodNetwork, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Sylvia, Louisa; Deckersbach, Thilo] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Doederlein, Allen; Jewell, Lucinda] Depress & Bipolar Support Alliance, Chicago, IL USA. [Muskin, Alies] Anxiety & Depress Assoc Amer, Silver Spring, MD USA. [Walker, Muffy] Int Bipolar Fdn, San Diego, CA USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 50 Stanford St,5th Floor, Boston, MA 02114 USA. EM anierenberg@partners.org FU PCORI [PPRN-1306-04925] FX Support for this commentary was received from PCORI PPRN-1306-04925. NR 16 TC 1 Z9 1 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2015 VL 76 IS 4 BP E528 EP E530 DI 10.4088/JCP.14com09570 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CI8DA UT WOS:000354997500012 PM 25919850 ER PT J AU Pietrzak, RH Sumner, JA Aiello, AE Uddin, M Neumeister, A Guffanti, G Koenen, KC AF Pietrzak, Robert H. Sumner, Jennifer A. Aiello, Allison E. Uddin, Monica Neumeister, Alexander Guffanti, Guia Koenen, Karestan C. TI Association of the rs2242446 Polymorphism in the Norepinephrine Transporter Gene SLC6A2 and Anxious Arousal Symptoms of Posttraumatic Stress Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID PANIC DISORDER C1 [Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT 06516 USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sumner, Jennifer A.; Guffanti, Guia; Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Aiello, Allison E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Uddin, Monica] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Uddin, Monica] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Neumeister, Alexander] NYU, Dept Radiol, Sch Med, New York, NY 10016 USA. RP Pietrzak, RH (reprint author), VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu FU National Institutes of Health [R01DA022720, R01DA022720-S1 [PhenX], R01DA022720-S1 [Supplement], RC1MH088283]; US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder FX This research was funded by National Institutes of Health grants (R01DA022720, R01DA022720-S1 [PhenX], R01DA022720-S1 [Supplement], and RC1MH088283). Preparation of this report was supported in part by the US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder and a private donation. NR 8 TC 3 Z9 3 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2015 VL 76 IS 4 BP E537 EP E538 DI 10.4088/JCP.14l09346 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CI8DA UT WOS:000354997500015 PM 25919853 ER PT J AU Clark, TK Newman, MC Oman, CM Merfeld, DM Young, LR AF Clark, Torin K. Newman, Michael C. Oman, Charles M. Merfeld, Daniel M. Young, Laurence R. TI Human perceptual overestimation of whole body roll tilt in hypergravity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE roll tilt; orientation perception; human; hypergravity; vestibular ID SHORT-RADIUS CENTRIFUGATION; INNERVATING OTOLITH ORGANS; GRAVITO-INERTIAL CUES; QUALITATIVELY DIFFERENT MECHANISMS; VISUAL ORIENTATION CONSTANCY; PERCEIVED SELF-ORIENTATION; HUMAN SPATIAL ORIENTATION; MOTION SICKNESS; SEMICIRCULAR CANALS; SQUIRREL-MONKEY AB Hypergravity provides a unique environment to study human perception of orientation. We utilized a long-radius centrifuge to study perception of both static and dynamic whole body roll tilt in hypergravity, across a range of angles, frequencies, and net gravito-inertial levels (referred to as G levels). While studies of static tilt perception in hypergravity have been published, this is the first to measure dynamic tilt perception (i.e., with time-varying canal stimulation) in hypergravity using a continuous matching task. In complete darkness, subjects reported their orientation perception using a haptic task, whereby they attempted to align a hand-held bar with their perceived horizontal. Static roll tilt was overestimated in hypergravity, with more overestimation at larger angles and higher G levels, across the conditions tested (overestimated by similar to 35% per additional G level, P < 0.001). As our primary contribution, we show that dynamic roll tilt was also consistently overestimated in hypergravity (P < 0.001) at all angles and frequencies tested, again with more overestimation at higher G levels. The overestimation was similar to that for static tilts at low angular velocities but decreased at higher angular velocities (P < 0.006), consistent with semicircular canal sensory integration. To match our findings, we propose a modification to a previous Observer-type canal-otolith interaction model. Specifically, our data were better modeled by including the hypothesis that the central nervous system treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. This modified model was able to simulate quantitatively both the static and the dynamic roll tilt overestimation in hypergravity measured experimentally. C1 [Clark, Torin K.; Oman, Charles M.; Young, Laurence R.] MIT, Man Vehicle Lab, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. [Clark, Torin K.] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. [Newman, Michael C.] Natl Aerosp Training & Res Ctr, Southampton, PA USA. [Merfeld, Daniel M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Jenks Vestibular Physiol Lab,Dept Otol & Laryngol, Boston, MA USA. RP Clark, TK (reprint author), MIT, Man Vehicle Lab, 77 Massachusetts Ave 37-219, Cambridge, MA 02139 USA. EM tkc@mit.edu FU National Space Biomedical Research Institute (NSBRI) through National Aeronautics and Space Administration [NCC9-58]; National Space Biomedical Research Institute (NSBRI) via National Institute of Deafness and Other Communications Disorders [R01-DC-04158]; NASTAR Center FX This work was supported by the National Space Biomedical Research Institute (NSBRI) through National Aeronautics and Space Administration Grant NCC9-58 (to T. K. Clark, C. M. Oman, and L. R. Young) and via National Institute of Deafness and Other Communications Disorders Grant R01-DC-04158 (to D. M. Merfeld). We also thank Bill Mitchell and NASTAR Center for additional project support. NR 116 TC 3 Z9 3 U1 0 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR 1 PY 2015 VL 113 IS 7 BP 2062 EP 2077 DI 10.1152/jn.00095.2014 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CI8EA UT WOS:000355000900009 PM 25540216 ER PT J AU Fedorenko, E Fillmore, P Smith, K Bonilha, L Fridriksson, J AF Fedorenko, Evelina Fillmore, Paul Smith, Kimberly Bonilha, Leonardo Fridriksson, Julius TI The superior precentral gyrus of the insula does not appear to be functionally specialized for articulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE articulation; Broca's area; fMRI; insula; SPGI ID SPEECH MOTOR CONTROL; BRAIN REGION; BROCAS AREA; APRAXIA; CORTEX; FMRI; MRI; APHASIA; JAW; LATERALIZATION AB Broca (Broca P. Bull Soc Anat Paris 36: 330-357, 1861) influentially argued that posterior left inferior frontal gyrus supports speech articulation. According to an alternative proposal (e.g., Dronkers NF. Nature 384: 159-161, 1996; Wise RJ, Greene J, Buchel C, Scott SK. Lancet 353: 1057-1061, 1999; Baldo JV, Wilkins DP, Ogar J, Willock S, Dronkers NF. Cortex 47: 800-807, 2011), a region in the anterior insula [specifically, the superior precentral gyrus of the insula (SPGI)] is the seat of articulatory abilities. Moreover, Dronkers and colleagues have argued that the SPGI is functionally specialized for (complex) speech articulation. Here, we evaluate this claim using individual-subject functional MRI (fMRI) analyses (e.g., Fedorenko E, Hsieh PJ, Nieto-Castanon A, Whitfield-Gabrieli S, Kanwisher N. J Neurophysiol 104: 1177-1194, 2010). We find that the SPGI responds weakly, if at all, during articulation (parts of Broca's area respond 3-4 times more strongly) and does not show a stronger response to higher articulatory demands. This holds regardless of whether the SPGI is defined functionally (by selecting the most articulation-responsive voxels in the vicinity of the SPGI in each subject individually) or anatomically (by using masks drawn on each individual subject's anatomy). Critically, nonspeech oral movements activate the SPGI more strongly than articulation, especially under the anatomical definition of the SPGI. In line with Hillis et al. (Hillis AE, Work M, Barker PB, Jacobs MA, Breese EL, Maurer K. Brain 127: 1479-1487, 2004; also Trupe L, Varma DD, Gomez Y, Race D, Leigh R, Hillis AE, Gottesman RF. Stroke 44: 740-744, 2013), we argue that previous links between the SPGI, and perhaps anterior insula more generally, and articulation may be due to its high base rate of ischemic damage (and activation in fMRI; Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD. Nat Methods 8: 665-670, 2011), combined with its proximity to regions that more directly support speech articulation, such as the precentral gyrus or the posterior aspects of the inferior frontal gyrus (Richardson JD, Fillmore P, Rorden C, Lapointe LL, Fridriksson J. Brain Lang 123: 125-130, 2012), and thus susceptibility to joint damage. C1 [Fedorenko, Evelina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fillmore, Paul; Smith, Kimberly; Fridriksson, Julius] Univ S Carolina, Columbia, SC 29208 USA. [Bonilha, Leonardo] Med Univ S Carolina, Charleston, SC USA. RP Fedorenko, E (reprint author), MGH, Dept Psychiat, Bldg 149,E 13th St,Rm 2624, Charlestown, MA 02129 USA. EM evelina.fedorenko@mgh.harvard.edu OI Fillmore, Paul/0000-0002-9997-2170 FU National Institute of Deafness and Other Communications Disorders [DC-009571]; National Institute of Child Health and Human Development Grant [HD-057522]; Simons Center for the Social Brain at MIT Grant FX This work was supported by National Institute of Deafness and Other Communications Disorders Grant DC-009571 (to J. Fridriksson), National Institute of Child Health and Human Development Grant HD-057522 (to E. Fedorenko), and the Simons Center for the Social Brain at MIT Grant (to E. Fedorenko). NR 60 TC 1 Z9 1 U1 4 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR 1 PY 2015 VL 113 IS 7 BP 2376 EP 2382 DI 10.1152/jn.00214.2014 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CI8EA UT WOS:000355000900036 PM 25632073 ER PT J AU Bajpayee, AG Scheu, A Vega, RD Varady, NH Yannatos, IA Porter, RM Grodzinsky, AJ AF Bajpayee, A. G. Scheu, A. Vega, R. D. Varady, N. H. Yannatos, I. A. Porter, R. M. Grodzinsky, A. J. TI INTRA-CARTILAGE DELIVERY OF DEXAMETHASONE FROM AVIDIN, A CATIONIC DRUG CARRIER, ATTENUATES INJURY INDUCED CATABOLIC EFFECTS IN KNEE JOINTS OF MATURE RABBITS IN VIVO SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) on Osteoarthritis CY APR 30-MAY 03, 2015 CL Seattle, WA SP Osteoarthritis Res Soc Int C1 [Bajpayee, A. G.; Varady, N. H.; Grodzinsky, A. J.] MIT, Cambridge, MA 02139 USA. [Scheu, A.] Clin Alemana Santiago, Santiago, Chile. [Vega, R. D.; Porter, R. M.] BIDMC, Boston, MA USA. Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2015 VL 23 SU 2 MA 199 BP A139 EP A140 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CI8VC UT WOS:000355048800229 ER PT J AU Suri, P Lorbergs, A Travison, TG Meng, CA Jarraya, M Guermazi, A Samelson, EJ AF Suri, P. Lorbergs, A. Travison, T. G. Meng, C. -A. Jarraya, M. Guermazi, A. Samelson, E. J. TI PHYSICAL ACTIVITY AND 6-YEAR INCIDENCE OF FACET JOINT OSTEOARTHRITIS IN WOMEN AND MEN: THE FRAMINGHAM STUDY SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) on Osteoarthritis CY APR 30-MAY 03, 2015 CL Seattle, WA SP Osteoarthritis Res Soc Int C1 [Suri, P.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Suri, P.] Harvard Univ, Sch Med, Boston, MA USA. [Suri, P.] Hebrew SeniorLife, Boston, MA USA. [Suri, P.] Mercy Hlth, Philadelphia, PA USA. [Suri, P.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Suri, P.] Harvard Univ, Sch Med, Hebrew SeniorLife, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2015 VL 23 SU 2 MA 270 BP A176 EP A176 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CI8VC UT WOS:000355048800300 ER PT J AU Khanam, F Abu Sayeed, M Choudhury, FK Sheikh, A Ahmed, D Goswami, D Hossain, ML Brooks, A Calderwood, SB Charles, RC Cravioto, A Ryan, ET Qadri, F AF Khanam, Farhana Abu Sayeed, Md. Choudhury, Feroza Kaneez Sheikh, Alaullah Ahmed, Dilruba Goswami, Doli Hossain, Md. Lokman Brooks, Abdullah Calderwood, Stephen B. Charles, Richelle C. Cravioto, Alejandro Ryan, Edward T. Qadri, Firdausi TI Typhoid Fever in Young Children in Bangladesh: Clinical Findings, Antibiotic Susceptibility Pattern and Immune Responses SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID VACCINE; CELL; IMMUNIZATION; BACTEREMIA; HUMANS AB Background Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. Methods As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. Principal Findings We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. Conclusions This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest can be used as marker of recent typhoid fever, even in young children. C1 [Khanam, Farhana; Abu Sayeed, Md.; Choudhury, Feroza Kaneez; Sheikh, Alaullah; Ahmed, Dilruba; Goswami, Doli; Hossain, Md. Lokman; Brooks, Abdullah; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Bangladesh Icddr B, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Sheikh, Alaullah] Washington Univ, Div Biol & Biomed Sci, Mol Microbiol & Microbial Pathogenesis Program, St Louis, MO USA. [Calderwood, Stephen B.; Charles, Richelle C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Calderwood, Stephen B.; Charles, Richelle C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Khanam, F (reprint author), Int Ctr Diarrhoeal Dis Res, Bangladesh Icddr B, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU icddr,b; National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI100023]; National Institutes of Health [AI058935, K08 AI089721]; Fogarty International Center [TW005572]; Bill and Melinda Gates Foundation [OPP50419]; SIDA [54100020, 51060029] FX This work was supported by the icddr,b and grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI100023 [ETR, FQ]); AI058935 [SBC, ETR and FQ]) and Career Development Award K08 AI089721 [RCC], as well as a Fogarty International Center Training Grant in Vaccine Development and Public Health (TW005572 [FK, MAS, AS and FQ]), Bill and Melinda Gates Foundation (Grant no. OPP50419) and also SIDA fund (54100020, 51060029). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 7 Z9 7 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2015 VL 9 IS 4 AR e0003619 DI 10.1371/journal.pntd.0003619 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CI7VF UT WOS:000354972200016 PM 25849611 ER PT J AU Lee, SP Klinker, LE Ptaszek, L Work, J Liu, C Quivara, F Webb, C Dagdeviren, C Wright, JA Ruskin, JN Slepian, M Huang, Y Mansour, M Rogers, JA Ghaffari, R AF Lee, Stephen P. Klinker, Lauren E. Ptaszek, Leon Work, John Liu, Cliff Quivara, Fernando Webb, Chad Dagdeviren, Canan Wright, John A. Ruskin, Jeremy N. Slepian, Marvin Huang, Yonggang Mansour, Moussa Rogers, John A. Ghaffari, Roozbeh TI Catheter-Based Systems With Integrated Stretchable Sensors and Conductors in Cardiac Electrophysiology SO PROCEEDINGS OF THE IEEE LA English DT Article DE Flexible electronics; biosensors; semiconductors; microfabrication; electrophysiology; vasculature; biomedical devices ID PERSISTENT ATRIAL-FIBRILLATION; PULMONARY VEIN ISOLATION; FOLLOW-UP; FOCAL IMPULSE; GLOBAL BURDEN; ABLATION; RHYTHM; MANAGEMENT; THERAPY; ROTORS AB Established classes of high-performance electronics have driven advances in interventional biomedicine. However, the large size, planar geometry and stiff mechanical properties of standard conventional electronics employed in medical devices give rise to important integration challenges with soft biological tissue. Stretchable and flexible biointegrated electronics could improve treatment procedures across a broad range of applications, including cardiac, neural and endovascular therapies. Here we present novel mechanics, materials and integration strategies for this new class of bioelectronics onboard minimally invasive catheter based systems. Co-located arrays of sensors and actuators affixed to cardiac and angioplasty balloon catheters capture new sensory information during ablation procedures, offering physicians the ability to adjust placement and treatment intra-procedurally. New circuit topologies, enabled by stretchable electronics, also overcome long standing challenges associated with transmitting vast amounts of data through narrow catheter lumens, thus allowing for a large number of sensors to be multiplexed for mapping electrophysiological activity with high spatiotemporal resolution and with a minimal number of routing wires. We present representative examples that highlight the clinical significance of soft bio-integrated electronics, along with the mechanics and processes that enable this technology. C1 [Lee, Stephen P.; Klinker, Lauren E.; Work, John; Liu, Cliff; Quivara, Fernando; Wright, John A.; Ghaffari, Roozbeh] MC10 Inc, Cambridge, MA 02140 USA. [Ptaszek, Leon; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA 02140 USA. [Webb, Chad; Dagdeviren, Canan; Rogers, John A.] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA. [Slepian, Marvin] Univ Arizona, Dept Med, Tucson, AZ 85724 USA. [Slepian, Marvin] Univ Arizona, Dept Biomed Engn, Tucson, AZ 85724 USA. [Huang, Yonggang] Northwestern Univ, Dept Civil & Environm Engn, Evanston, IL 60208 USA. RP Lee, SP (reprint author), MC10 Inc, Cambridge, MA 02140 USA. EM rghaffari@mc10inc.com RI Huang, Yonggang/B-6998-2009; Rogers, John /L-2798-2016; OI Lee, Stephen/0000-0002-8521-8652 NR 23 TC 3 Z9 3 U1 4 U2 18 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9219 EI 1558-2256 J9 P IEEE JI Proc. IEEE PD APR PY 2015 VL 103 IS 4 SI SI BP 682 EP 689 DI 10.1109/JPROC.2015.2401596 PG 8 WC Engineering, Electrical & Electronic SC Engineering GA CJ1NL UT WOS:000355250200014 ER PT J AU Janne, PA Ahn, MJ Kim, DW Kim, SW Planchard, D Ramalingam, SS Frewer, P Cantarini, M Ghiorghiu, S Yang, JCH AF Jaenne, P. A. Ahn, M. -J. Kim, D. -W. Kim, S. -W. Planchard, D. Ramalingam, S. S. Frewer, P. Cantarini, M. Ghiorghiu, S. Yang, J. C. -H. TI A PHASE I STUDY OF AZD9291 IN PATIENTS WITH EGFR-TKI-RESISTANT ADVANCED NSCLC - UPDATED PROGRESSION FREE SURVIVAL AND DURATION OF RESPONSE DATA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT European Lung Cancer Conference (ELCC) CY APR 18, 2015 CL Geneva, SWITZERLAND C1 [Jaenne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Ahn, M. -J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Internal Med,Hematol,Oncol, Seoul, South Korea. [Kim, D. -W.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Kim, S. -W.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Planchard, D.] Gustave Roussy, Dept Med Oncol & Translat Res, Thorac Unit, Villejuif, France. [Ramalingam, S. S.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Frewer, P.] Astra Zeneca, ECD Biometr, Macclesfield, Cheshire, England. [Cantarini, M.] Astra Zeneca, Global Med Dept, Oncol, Macclesfield, Cheshire, England. [Ghiorghiu, S.] Astra Zeneca, Global Med Dev, Luton, Herts, England. [Yang, J. C. -H.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. NR 0 TC 1 Z9 1 U1 4 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2015 VL 26 SU 1 MA LBA3 DI 10.1093/annonc/mdv128.5 PG 1 WC Oncology SC Oncology GA CI4NW UT WOS:000354728700086 ER PT J AU Kerstein, D Gettinger, S Gold, K Langer, CJ Shaw, AT Bazhenova, LA Salgia, R Dorer, DJ Conlan, MG Camidge, DR AF Kerstein, D. Gettinger, S. Gold, K. Langer, C. J. Shaw, A. T. Bazhenova, L. A. Salgia, R. Dorer, D. J. Conlan, M. G. Camidge, D. R. TI EVALUATION OF ANAPLASTIC LYMPHOMA KINASE (ALK) INHIBITOR BRIGATINIB [AP26113] IN PATIENTS (PTS) WITH ALK plus NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN METASTASES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT European Lung Cancer Conference (ELCC) CY APR 18, 2015 CL Geneva, SWITZERLAND C1 [Kerstein, D.; Conlan, M. G.] ARIAD Pharmaceut Inc, Clin Res, Cambridge, MA USA. [Gettinger, S.] Yale Univ, Sch Med Med Oncol, Thorac Oncol Program, New Haven, NJ USA. [Gold, K.] Univ Texas MD Anderson Canc Ctr, Dept Thoracic Head & Neck Med Oncol, Houston, TX 77030 USA. [Langer, C. J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Shaw, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Bazhenova, L. A.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Salgia, R.] Univ Chicago, Med Ctr, Thorac Oncol, Chicago, IL 60637 USA. [Dorer, D. J.] ARIAD Pharmaceut Inc, Biostat, Cambridge, MA USA. [Camidge, D. R.] Univ Colorado, Ctr Canc, Thorac Oncol, Aurora, CO USA. NR 0 TC 1 Z9 1 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2015 VL 26 SU 1 MA LBA4 DI 10.1093/annonc/mdv128.6 PG 1 WC Oncology SC Oncology GA CI4NW UT WOS:000354728700087 ER PT J AU Rosell, R Gettinger, S Bazhenova, LA Langer, CJ Salgia, R Gold, K Shaw, AT Dorer, DJ Kerstein, D Camidge, DR AF Rosell, R. Gettinger, S. Bazhenova, L. A. Langer, C. J. Salgia, R. Gold, K. Shaw, A. T. Dorer, D. J. Kerstein, D. Camidge, D. R. TI PHASE 1/2 STUDY OF AP26113 IN PATIENTS (PTS) WITH ADVANCED MALIGNANCIES, INCLUDING ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC): ANALYSIS OF SAFETY AND EFFICACY AT SELECTED PHASE 2 DOSES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT European Lung Cancer Conference (ELCC) CY APR 18, 2015 CL Geneva, SWITZERLAND C1 [Rosell, R.] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol ICO Badalona, Med Oncol Serv, Badalona, Spain. [Gettinger, S.] Yale Univ, Sch Med Med Oncol, Thorac Oncol Program, New Haven, CT USA. [Bazhenova, L. A.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Langer, C. J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Salgia, R.] Univ Chicago, Med Ctr, Thorac Oncol, Chicago, IL 60637 USA. [Gold, K.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Shaw, A. T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Dorer, D. J.] ARIAD Pharmaceut Inc, Biostat, Cambridge, MA 02139 USA. [Kerstein, D.] ARIAD Pharmaceut Inc, Clin Res, Cambridge, MA 02139 USA. [Camidge, D. R.] Univ Colorado, Ctr Canc, Thorac Oncol, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2015 VL 26 SU 1 MA 99O DI 10.1093/annonc/mdv050.3 PG 1 WC Oncology SC Oncology GA CI4NW UT WOS:000354728700044 ER PT J AU Criner, GJ Bourbeau, J Diekemper, RL Ouellette, DR Goodridge, D Hernandez, P Curren, K Balter, MS Bhutani, M Camp, PG Celli, BR Dechman, G Dransfield, MT Fiel, SB Foreman, MG Hanania, NA Ireland, BK Marchetti, N Marciniuk, DD Mularski, RA Ornelas, J Road, JD Stickland, MK AF Criner, Gerard J. Bourbeau, Jean Diekemper, Rebecca L. Ouellette, Daniel R. Goodridge, Donna Hernandez, Paul Curren, Kristen Balter, Meyer S. Bhutani, Mohit Camp, Pat G. Celli, Bartolome R. Dechman, Gail Dransfield, Mark T. Fiel, Stanley B. Foreman, Marilyn G. Hanania, Nicola A. Ireland, Belinda K. Marchetti, Nathaniel Marciniuk, Darcy D. Mularski, Richard A. Ornelas, Joseph Road, Jeremy D. Stickland, Michael K. TI Prevention of Acute Exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; IMPROVING PRIMARY-CARE; COMPLEX INTERVENTIONS; CHRONIC ILLNESS; RECOMMENDATIONS; MANAGEMENT; DIAGNOSIS; OUTCOMES; QUALITY; UPDATE C1 [Criner, Gerard J.] Temple Univ, Sch Med, Philadelphia, PA 19140 USA. [Bourbeau, Jean] McGill Univ, Resp Epidemiol & Clin Res Unit, Montreal Chest Inst, Ctr Hlth, Montreal, PQ, Canada. [Diekemper, Rebecca L.; Ornelas, Joseph] Amer Coll Chest Phys, Glenview, IL USA. [Ouellette, Daniel R.] Henry Ford Hlth Syst, Detroit, MI USA. [Goodridge, Donna] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 0W0, Canada. [Hernandez, Paul] Dalhousie Univ, Dept Med, Halifax, NS, Canada. [Dechman, Gail] Dalhousie Univ, Sch Physiotherapy, Halifax, NS, Canada. [Curren, Kristen] Canadian Thorac Soc, Ottawa, ON, Canada. [Balter, Meyer S.] Univ Toronto, Div Respirol, Toronto, ON, Canada. [Bhutani, Mohit] Univ Alberta, Edmonton, AB, Canada. [Camp, Pat G.] Univ British Columbia, Dept Phys Therapy, Vancouver, BC V5Z 1M9, Canada. [Celli, Bartolome R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Dransfield, Mark T.] Univ Alabama Birmingham, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Fiel, Stanley B.] Atlantic Hlth Syst, Med Ctr, Morristown, NJ USA. [Foreman, Marilyn G.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Hanania, Nicola A.] Baylor Coll Med, Houston, TX 77030 USA. [Ireland, Belinda K.] TheEvidenceDoc LLC, Pacifi, MO USA. [Marchetti, Nathaniel] Temple Univ, Sch Med, Philadelphia, PA USA. [Marciniuk, Darcy D.] Univ Saskatchewan, Div Respirol Crit Care & Sleep Med, Royal Univ Hosp, Saskatoon, SK, Canada. [Mularski, Richard A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Road, Jeremy D.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Stickland, Michael K.] Univ Alberta, Div Pulm Med, Edmonton, AB, Canada. RP Criner, GJ (reprint author), Temple Univ, Sch Med, Dept Pulm & Crit Care Med, 745 Parkinson Pavilion,3401 N Broad St, Philadelphia, PA 19140 USA. EM gerard.criner@tuhs.temple.edu FU NHLBI NIH HHS [K01 HL092601]; NIMHD NIH HHS [S21 MD000101] NR 32 TC 14 Z9 15 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2015 VL 147 IS 4 BP 883 EP 893 DI 10.1378/chest.14-1677 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VT UT WOS:000354606300021 PM 25320966 ER PT J AU Criner, GJ Bourbeau, J Diekemper, RL Ouellette, DR Goodridge, D Hernandez, P Curren, K Balter, MS Bhutani, M Camp, PG Celli, BR Dechman, G Dransfield, MT Fiel, SB Foreman, MG Hanania, NA Ireland, BK Marchetti, N Marciniuk, DD Mularski, RA Ornelas, J Road, JD Stickland, MK AF Criner, Gerard J. Bourbeau, Jean Diekemper, Rebecca L. Ouellette, Daniel R. Goodridge, Donna Hernandez, Paul Curren, Kristen Balter, Meyer S. Bhutani, Mohit Camp, Pat G. Celli, Bartolome R. Dechman, Gail Dransfield, Mark T. Fiel, Stanley B. Foreman, Marilyn G. Hanania, Nicola A. Ireland, Belinda K. Marchetti, Nathaniel Marciniuk, Darcy D. Mularski, Richard A. Ornelas, Joseph Road, Jeremy D. Stickland, Michael K. TI Prevention of Acute Exacerbations of COPD American College of Chest Physicians and Canadian Thoracic Society Guideline SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; LONG-TERM TREATMENT; FLUTICASONE PROPIONATE/SALMETEROL 250/50; INHALED ANTICHOLINERGIC BRONCHODILATOR; SMOKING-CESSATION INTERVENTION; CLINICAL-PRACTICE GUIDELINE; CHRONIC RESPIRATORY-FAILURE; SLOW-RELEASE THEOPHYLLINE AB BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS: This guideline is unique because it provides an up-to-date, rigorous, evidencebased analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations. C1 [Criner, Gerard J.] Temple Univ, Sch Med, Philadelphia, PA 19140 USA. [Bourbeau, Jean] McGill Univ, Ctr Hlth, Resp Epidemiol & Clin Res Unit, Montreal Chest Inst, Montreal, PQ, Canada. [Diekemper, Rebecca L.; Ornelas, Joseph] Amer Coll Chest Phys, Glenview, IL USA. [Ouellette, Daniel R.] Henry Ford Hlth Syst, Detroit, MI USA. [Goodridge, Donna] Univ Saskatchewan, Coll Med, Saskatoon, SK S7N 0W0, Canada. [Hernandez, Paul] Dalhousie Univ, Dept Med, Halifax, NS, Canada. [Dechman, Gail] Dalhousie Univ, Sch Physiotherapy, Halifax, NS, Canada. [Curren, Kristen] Canadian Thorac Soc, Ottawa, ON, Canada. [Balter, Meyer S.] Univ Toronto, Div Respirol, Toronto, ON, Canada. [Bhutani, Mohit] Univ Alberta, Edmonton, AB, Canada. [Camp, Pat G.] Univ British Columbia, Dept Phys Therapy, Vancouver, BC V5Z 1M9, Canada. [Celli, Bartolome R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Dransfield, Mark T.] Univ Alabama Birmingham, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Fiel, Stanley B.] Atlantic Hlth Syst, Med Ctr, Morristown, NJ USA. [Foreman, Marilyn G.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Hanania, Nicola A.] Baylor Coll Med, Houston, TX 77030 USA. [Ireland, Belinda K.] TheEvidenceDoc LLC, Pacific, MO USA. [Marchetti, Nathaniel] Temple Univ, Sch Med, Philadelphia, PA USA. [Marciniuk, Darcy D.] Univ Saskatchewan, Royal Univ Hosp, Div Respirol Crit Care & Sleep, Saskatoon, SK, Canada. [Mularski, Richard A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Road, Jeremy D.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Stickland, Michael K.] Univ Alberta, Div Pulm Med, Edmonton, AB, Canada. RP Criner, GJ (reprint author), Temple Univ, Sch Med, Dept Pulm & Crit Care Med, 745 Parkinson Pavilion,3401 N Broad St, Philadelphia, PA 19140 USA. EM gerard.criner@tuhs.temple.edu OI Goodridge, Donna/0000-0002-8680-8646; Foreman, Marilyn/0000-0002-9405-7475 FU American College of Chest Physicians; Canadian Thoracic Society FX The American College of Chest Physicians and the Canadian Thoracic Society supported the development this article and the innovations addressed within. NR 284 TC 41 Z9 44 U1 4 U2 18 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2015 VL 147 IS 4 BP 894 EP 942 DI 10.1378/chest.14-1676 PG 49 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VT UT WOS:000354606300022 PM 25321320 ER PT J AU Muellerova, H Maselli, DJ Locantore, N Vestbo, J Hurst, JR Wedzicha, JA Bakke, P Agusti, A Anzueto, A AF Muellerova, Hana Maselli, Diego J. Locantore, Nicholas Vestbo, Jorgen Hurst, John R. Wedzicha, Jadwiga A. Bakke, Per Agusti, Alvar Anzueto, Antonio CA ECLIPSE Investigators TI Hospitalized Exacerbations of COPD Risk Factors and Outcomes in the ECLIPSE Cohort SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION DECLINE; QUALITY-OF-LIFE; HEALTH-STATUS; GLOBAL BURDEN; TIME-COURSE; MORTALITY; PREDICTORS; SEVERITY; RECOVERY AB OBJECTIVE: Exacerbations of COPD requiring hospital admission have important clinical and societal implications. We sought to investigate the incidence, recurrence, risk factors, and mortality of patients with COPD exacerbations requiring hospital admission compared with those without hospital admission during 3-year follow-up. Patients with COPD (N = 2,138) were identified from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) observational cohort. METHODS: An analysis of time to first event of hospital admission was performed using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders. RESULTS: Of the 2,138 patients, 670 (31%) reported a total of 1,452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio, 2.71; 95% CI, 2.24-3.29; P < .001). Other risk factors included more severe airflow limitation, poorer health status, older age, radiologic evidence of emphysema, and higher WBC count. Having been hospitalized for exacerbation significantly increased the risk of mortality (P,.001). CONCLUSIONS: Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. Patients with COPD at a high risk for hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis. C1 [Muellerova, Hana] GlaxoSmithKline R&D, Resp Epidemiol, Uxbridge, Middx, England. [Maselli, Diego J.; Anzueto, Antonio] South Texas Vet Hlth Care Syst, Audie L Murphy Hosp, San Antonio, TX USA. [Maselli, Diego J.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Crit Care Med, Div Pulm Dis, San Antonio, TX 78229 USA. [Locantore, Nicholas] GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC USA. [Vestbo, Jorgen] Gentofte, Hellerup, Denmark. [Vestbo, Jorgen] Univ Manchester, Resp Res Grp, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Hurst, John R.] UCL, Ctr Inflammat & Tissue Repair, London, England. [Wedzicha, Jadwiga A.] UCL, Ctr Resp Med, London, England. [Bakke, Per] Univ Bergen, Dept Clin Sci, Bergen, Norway. [Bakke, Per] Haukeland Hosp, Dept Thorac Med, N-5021 Bergen, Norway. [Agusti, Alvar] Univ Barcelona, Thorax Inst, Hosp Clin, IDIBAPS, Barcelona, Spain. [Agusti, Alvar] CIBER Enfermedades Resp, FISIB, Mallorca, Spain. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, 7400 Merton Minter,MC111E, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu RI Agusti Garcia-Navarro, Alvar/F-4474-2015; OI Agusti Garcia-Navarro, Alvar/0000-0003-3271-3788; MacNee, William/0000-0002-3692-1448; Mullerova, Hana/0000-0002-0949-0101 FU GlaxoSmithKline FX The ECLIPSE study was funded by GlaxoSmithKline. NR 52 TC 19 Z9 19 U1 2 U2 6 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2015 VL 147 IS 4 BP 999 EP 1007 DI 10.1378/chest.14-0655 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VT UT WOS:000354606300029 ER PT J AU Buchbinder, EI McDermott, DF AF Buchbinder, Elizabeth I. McDermott, David F. TI Cytotoxic T-Lymphocyte Antigen-4 Blockade in Melanoma SO CLINICAL THERAPEUTICS LA English DT Review DE autoimmunity; checkpoint inhibitor; CTLA4; ipilimumab ID METASTATIC MELANOMA; CTLA-4 BLOCKADE; PHASE-I/II; PROSTATE-CANCER; PLUS IPILIMUMAB; ADVERSE EVENTS; TRIAL; THERAPY; CELLS; ANTI-CTLA-4 AB Purpose: Melanoma is an aggressive malignancy that has a complex relationship with the host immune system. Immunotherapies have long been a mainstay of melanoma therapy, and advanced therapies continue to be effective in treating this disease. Immune checkpoint blockade has proven to be a novel target in melanoma, with the approval of cytotoxic T-lymphocyte antigen-4 (CTLA-4)-targeted therapy. This review evaluates the role of CTLA-4-targeted therapies in the treatment of metastatic melanoma, with a focus on mechanisms, efficacy, toxicity, and future directions of this therapy. Methods: A search was performed in PubMed to identify relevant clinical studies that explored the clinical experience with CTLA-4-targeted therapy in melanoma. Findings: Signaling through CTLA-4 causes deactivation of T cells after the initial stimulatory signals. Therapies that block CTLA-4 lead to increased T-cell function and an antitumor response in patients with metastatic melanoma. The adverse event profile of these agents is different from that seen with more traditional cancer therapies and consists of dermatitis, colitis, and other autoimrnune toxicities. In addition, the pattern of response is different from that seen with traditional cytotoxic therapies, with some patients experiencing initial progression followed by response and some patients having long-term durable responses. Implications: Extensive clinical evidence supports the use of CTLA-4-targeted agents in the treatment of metastatic melanoma. The durability of response seen in patients receiving these agents has changed the landscape for patients with melanoma. Combination therapies. and other agents with similar mechanisms warrant further exploration for the treatment of metastatic melanoma. (Clin Ther. 2015;37:755-763) (C) 2015 Elsevier HS Journals, Inc. All rights reserved. C1 [Buchbinder, Elizabeth I.] Dana Farber Canc Inst, Div Oncol, Boston, MA 02215 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Div Oncol, Boston, MA 02215 USA. RP Buchbinder, EI (reprint author), Dana Farber Canc Inst, Div Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM elizabeth_buchbinder@DFCI.harvard.edu NR 55 TC 9 Z9 9 U1 1 U2 5 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD APR PY 2015 VL 37 IS 4 BP 755 EP 763 DI 10.1016/j.clinthera.2015.02.003 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CI0IU UT WOS:000354421100009 PM 25746738 ER PT J AU Mahoney, KM Freeman, GJ McDermott, DF AF Mahoney, Kathleen M. Freeman, Gordon J. McDermott, David F. TI The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma SO CLINICAL THERAPEUTICS LA English DT Review DE melanoma; MPDL3280A; nivolumab; PD-1; PD-L1; pembrolizumab; pidilizumab; programmed cell death 1 ID T-CELL-ACTIVATION; PROGRAMMED DEATH-1; REGULATORY T; ANTI-PD-L1 ANTIBODY; INDUCED EXPRESSION; CARCINOMA PATIENTS; EFFECTOR FUNCTION; CLINICAL ACTIVITY; TUMOR-CELLS; PD-1 GENE AB Purpose: Blocking the interaction between the programmed cell death (PD)-1 protein and one of its ligands, PD-L1, has been reported to have impressive antitumor responses. Therapeutics targeting this pathway are currently in clinical trials. Pembrolizumab and nivolumab are the first of this anti-PD-1 pathway family of checkpoint inhibitors to gain accelerated approval from the US Food and Drug Administration (FDA) for the treatment of ipilimumab-refractory melanoma. Nivolumab has been associated with improved overall survival compared with dacarbazine in patients with previously untreated wild-type serine/threonine-protein kinase B-raf proto-oncogene BRAF melanoma. Although the most mature data are in the treatment of melanoma, the FDA has granted approval of nivolumab for squamous cell lung cancer and the breakthrough therapy designation to immune-checkpoint inhibitors for use in other cancers: nivolumab, an anti-PD-1 monoclonal antibody, for Hodgkin lymphoma, and MPDL-3280A, an anti-PD-L1 monoclonal antibody, for bladder cancer and non-small cell lung cancer. Here we review the literature on PD-1 and PD-L1 blockade and focus on the reported clinical studies that have included patients with melanoma. Methods: Pub Med was searched to identify relevant clinical studies of PD-1/PD-L1-targeted therapies in melanoma. A review of data from the current trials on clinicaltrial.gov was incorporated, as well as data presented in abstracts at the 2014 annual meeting of the American Society of Clinical Oncology, given the limited number of published clinical trials on this topic. Findings: The anti-PD-1 and anti-PD-L1 agents have been reported to have impressive antitumor effects in several malignancies, including melanoma. The greatest clinical activity in unselected patients has been seen in melanoma. Tumor expression of PD-L1 is a suggestive, but inadequate, biomarker predictive of response to immune-checkpoint blockade. However, tumors expressing little or no PD-L1 are less likely to respond to PD-1 pathway blockade. Combination checkpoint blockade with PD-1 plus cytotoxic T-lymphocyte antigen (CTLA)-4 blockade appears to improve response rates in patients who are less likely to respond to single-checkpoint blockade. Toxicity with PD-1 blocking agents is less than the toxicity with previous immunotherapies (eg, interleukin 2, CTLA-4 blockade). Certain adverse events can be severe and potentially life threatening, but most can be prevented or reversed with close monitoring and appropriate management. Implications: This family of immune-checkpoint inhibitors benefits not only patients with metastatic melanoma but also those with historically less responsive tumor types. Although a subset of patients responds to single-agent blockade, the initial trial of checkpoint-inhibitor combinations has reported a potential to improve response rates. Combination therapies appear to be a means of increasing response rates, albeit with increased immune-related adverse events. As these treatments become available to patients, education regarding the recognition and management of immune-related effects of immune-checkpoint blockade will be essential for maximizing clinical benefit. (Clin Ther. 2015;37:764-782) (C) 2015 Elsevier HS Journals, Inc. All rights reserved. C1 [Mahoney, Kathleen M.; McDermott, David F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol & Oncol, Boston, MA 02215 USA. [Mahoney, Kathleen M.; Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Mahoney, KM (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM kmmah5@bidmc.harvard.edu FU National Institutes of Health National Cancer Institute [P50CA101942]; Claudia Adams Barr Program for Innovative Cancer Research; American Association for Cancer Research Basic Cancer Research Fellowship [14-40-01-MAHO]; American Society of Clinical Oncology Young Investigator Award from the Kidney Cancer Association; [U54CA163125]; [P01AI054456]; [U54CA16312]; [R01AI089955] FX This research was financially supported by a grant from the National Institutes of Health National Cancer Institute (P50CA101942; BIDMC); the Claudia Adams Barr Program for Innovative Cancer Research; an American Association for Cancer Research Basic Cancer Research Fellowship (14-40-01-MAHO); the American Society of Clinical Oncology Young Investigator Award from the Kidney Cancer Association (to K.M.).; and grants U54CA163125, P01AI054456, U54CA16312, and R01AI089955 (to G.J.F.; DFCI). NR 89 TC 57 Z9 60 U1 17 U2 54 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD APR PY 2015 VL 37 IS 4 BP 764 EP 782 DI 10.1016/j.clinthera.2015.02.018 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CI0IU UT WOS:000354421100010 PM 25823918 ER PT J AU Ishikawa, Y Maeda, M Pasham, M Aguet, F Tacheva-Grigorova, SK Masuda, T Yi, H Lee, SU Xu, J Teruya-Feldstein, J Ericsson, M Mullally, A Heuser, J Kirchhausen, T Maeda, T AF Ishikawa, Yuichi Maeda, Manami Pasham, Mithun Aguet, Francois Tacheva-Grigorova, Silvia K. Masuda, Takeshi Yi, Hai Lee, Sung-Uk Xu, Jian Teruya-Feldstein, Julie Ericsson, Maria Mullally, Ann Heuser, John Kirchhausen, Tom Maeda, Takahiro TI Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology SO HAEMATOLOGICA LA English DT Article ID TRANSFERRIN RECEPTOR; MYELOPROLIFERATIVE NEOPLASM; ERYTHROID-DIFFERENTIATION; ERYTHROBLASTIC ISLAND; MEDIATED ENDOCYTOSIS; ASSEMBLY PROTEIN; COATED PITS; CELL-LINE; IRON; ERYTHROPOIESIS AB Clathrin-dependent endocytosis is an essential cellular process shared by all cell types. Despite this, precisely how endocytosis is regulated in a cell-type-specific manner and how this key pathway functions physiologically or pathophysiologically remain largely unknown. PICALM, which encodes the clathrin adaptor protein PICALM, was originally identified as a component of the CALM/AF10 leukemia oncogene. Here we show, by employing a series of conditional Picalm knockout mice, that PICALM critically regulates transferrin uptake in erythroid cells by functioning as a cell-type-specific regulator of transferrin receptor endocytosis. While transferrin receptor is essential for the development of all hematopoietic lineages, Picalm was dispensable for myeloid and B-lymphoid development. Furthermore, global Picalm inactivation in adult mice did not cause gross defects in mouse fitness, except for anemia and a coat color change. Freeze-etch electron microscopy of primary erythroblasts and live-cell imaging of murine embryonic fibroblasts revealed that Picalm function is required for efficient clathrin coat maturation. We showed that the PICALM PIP2 binding domain is necessary for transferrin receptor endocytosis in erythroblasts and absolutely essential for erythroid development from mouse hematopoietic stem/progenitor cells in an erythroid culture system. We further showed that Picalm deletion entirely abrogated the disease phenotype in a Jak2(V617F) knock-in murine model of polycythemia vera. Our findings provide new insights into the regulation of cell-type-specific transferrin receptor endocytosis in vivo. They also suggest a new strategy to block cellular uptake of transferrin-bound iron, with therapeutic potential for disorders characterized by inappropriate red blood cell production, such as polycythemia vera. C1 [Ishikawa, Yuichi; Maeda, Manami; Lee, Sung-Uk; Maeda, Takahiro] City Hope Natl Med Ctr, Beckman Res Inst, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. [Ishikawa, Yuichi; Maeda, Manami; Masuda, Takeshi; Yi, Hai; Lee, Sung-Uk; Mullally, Ann; Maeda, Takahiro] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Ishikawa, Yuichi] Nagoya Univ, Grad Sch Med, Dept Hematol Oncol, Nagoya, Aichi 4648601, Japan. [Pasham, Mithun; Aguet, Francois; Tacheva-Grigorova, Silvia K.; Ericsson, Maria; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Pasham, Mithun; Tacheva-Grigorova, Silvia K.; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pasham, Mithun; Tacheva-Grigorova, Silvia K.; Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Yi, Hai] Gen Hosp Chengdu Mil Reg, Dept Hematol, Chengdu, Peoples R China. [Xu, Jian] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Dallas, TX 75390 USA. [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, Sloan Kettering Inst, New York, NY 10021 USA. [Heuser, John] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Maeda, T (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. EM tmaeda@partners.org FU National Institutes of Health [R01 GM075252]; Japan Society for the Promotion of Science (Young Researcher Overseas Visits Program for Vitalizing Brain Circulation fellowship); American Cancer Society [RSG-13-379-01-LIB] FX We thank members of COH Animal Resources and ARCH for colony maintenance; Walter Tsark for help and advice on generation of Picalm knockout mice; Robyn Roth for help on freeze-etch electron microscopy. Jing Zhang, Jiahai Shi and Harvey Lodish for sharing experimental protocols; Taisuke Kondo, Julio Valencia, Vincent Hearing, Barry Paw, Carlo Brugnara, Paul Schmidt and Mark Fleming for advice; Thomas Ludwig for ROSA26Cre-ERT2 mice; Jean Christophe Zeeh, Patrick Reeves, and Raphael Gaudin for technical advice; and Mai Suzuki and other members of the Maeda laboratory for help and advice. This work was supported in part by the National Institutes of Health (grant R01 GM075252 to TK), the Japan Society for the Promotion of Science (Young Researcher Overseas Visits Program for Vitalizing Brain Circulation fellowship to YI) and the American Cancer Society (grant RSG-13-379-01-LIB to TM). NR 52 TC 0 Z9 0 U1 1 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD APR PY 2015 VL 100 IS 4 BP 442 EP 454 DI 10.3324/haematol.2014.119537 PG 13 WC Hematology SC Hematology GA CI5HP UT WOS:000354786300018 ER PT J AU Romano, JG Smith, EE Liang, L Gardener, H Camp, S Shuey, L Cook, A Campo-Bustillo, I Khatri, P Bhatt, DL Fonarow, GC Sacco, RL Schwamm, LH AF Romano, Jose G. Smith, Eric E. Liang, Li Gardener, Hannah Camp, Sara Shuey, Laura Cook, Alison Campo-Bustillo, Iszet Khatri, Pooja Bhatt, Deepak L. Fonarow, Gregg C. Sacco, Ralph L. Schwamm, Lee H. TI Outcomes in Mild Acute Ischemic Stroke Treated With Intravenous Thrombolysis A Retrospective Analysis of the Get With the Guidelines-Stroke Registry SO JAMA NEUROLOGY LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; CONTROLLED-TRIAL; LIPID PROFILE; SCALE SCORES; SYMPTOMS; METAANALYSIS; THERAPY; PATIENT AB IMPORTANCE Mild strokes have been poorly represented in thrombolytic trials and only a few series have reported outcomes after treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA) after mild stroke. OBJECTIVE To report treatment complications and short-term outcomes in patients with mild stroke who have received treatment with IV rtPA. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of patients treated in the emergency department of hospitals that use the Get With the Guidelines-Stroke registry, a prospectively collected quality improvement registry used by hospitals across the United States. Patients were those admitted between May 1, 2010, and October 1, 2012, with acute ischemic stroke within 4.5 hours from symptom onset and a baseline National Institutes of Health Stroke Scale score of 5 or less. Univariable and multivariable analyses were performed to identify factors independently associated with discharge outcomes and treatment complications. INTERVENTION Intravenous rtPA. MAIN OUTCOMES AND MEASURES Treatment complications included symptomatic intracranial hemorrhage, life-threatening or serious systemic hemorrhage, other serious complications, and undetermined complications. The short-term outcomes analyzed were in-hospital mortality, discharge to home, independent ambulation at discharge, and length of stay. RESULTS Among 33 995 patients who arrived within 4.5 hours of symptom onset and were treated with IV rtPA, 7621 (22.4%) had a National Institutes of Health Stroke Scale score of 5 or less and 5910 had complete data for analysis. Treatment complications were infrequent: symptomatic intracranial hemorrhage, 1.8%; life-threatening or serious systemic hemorrhage, 0.2%; other serious complications, 1.8%; and complications of undetermined cause, 2.4%. Mortality was low (1.3%), but at discharge 30.3% could not ambulate independently, 29.4% could not go directly home, and 73.0% had a length of stay of 3 days or longer. Worse short-term outcomes were seen in older patients, African American patients, diabetic patients, and those who arrived by ambulance, after hours, or with a higher National Institutes of Health Stroke Scale score. CONCLUSIONS AND RELEVANCE Many patients with ischemic stroke treated with IV rtPA have a mild stroke. Symptomatic intracranial hemorrhage is infrequent, but approximately 30% of these patients are unable to return directly home or ambulate independently at discharge. Additional studies are needed to identify strategies to improve the outcomes in patients with mild stroke who receive thrombolysis. C1 [Romano, Jose G.; Gardener, Hannah; Campo-Bustillo, Iszet; Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Liang, Li] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Camp, Sara; Shuey, Laura; Cook, Alison] Amer Heart Assoc, Dallas, TX USA. [Khatri, Pooja] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Heart & Vasc Ctr,Dept Med, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Romano, JG (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, 1120 NW 14th St,Ste 1357, Miami, FL 33136 USA. EM jromano@med.miami.edu FU Genentech FX This work was supported by a grant from Genentech to the University of Miami. NR 51 TC 10 Z9 11 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2015 VL 72 IS 4 BP 423 EP 431 DI 10.1001/jamaneurol.2014.4354 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CH9KG UT WOS:000354353900010 PM 25642650 ER PT J AU Amariglio, RE Donohue, MC Marshall, GA Rentz, DM Salmon, DP Ferris, SH Karantzoulis, S Aisen, PS Sperling, RA AF Amariglio, Rebecca E. Donohue, Michael C. Marshall, Gad A. Rentz, Dorene M. Salmon, David P. Ferris, Steven H. Karantzoulis, Stella Aisen, Paul S. Sperling, Reisa A. CA Alzheimers Dis Cooperative Study TI Tracking Early Decline in Cognitive Function in Older Individuals at Risk for Alzheimer Disease Dementia The Alzheimer's Disease Cooperative Study Cognitive Function Instrument SO JAMA NEUROLOGY LA English DT Article ID COMPLAINTS; ADULTS; IMPAIRMENT; MEMORY; PROJECT AB IMPORTANCE Several large-scale Alzheimer disease (AD) secondary prevention trials have begun to target individuals at the preclinical stage. The success of these trials depends on validated outcome measures that are sensitive to early clinical progression in individuals who are initially asymptomatic. OBJECTIVE To investigate the utility of the Cognitive Function Instrument (CFI) to track early changes in cognitive function in older individuals without clinical impairment at baseline. DESIGN, SETTING, AND PARTICIPANTS Longitudinal study from February 2002 through February 2007 at participating Alzheimer's Disease Cooperative Study sites. Individuals were followed up annually for 48 months after the baseline visit. The study included 468 healthy older individuals (Clinical Dementia Rating scale [CDR] global scores of 0, above cutoff on the modified Mini-Mental State Examination and Free and Cued Selective Reminding Test) (mean [SD] age, 79.4 [3.6] years; age range, 75.0-93.8 years). All study participants and their study partners completed the self and partner CFIs annually. Individuals also underwent concurrent annual neuropsychological assessment and APOE genotyping. MAIN OUTCOMES AND MEASURES The CFI scores between clinical progressors (CDR score, >= 0.5) and nonprogressors (CDR score, 0) and between APOE epsilon 4 carriers and noncarriers were compared. Correlations of change between the CFI scores and neuropsychological performance were assessed longitudinally. RESULTS At 48 months, group differences between clinical progressors and non-progressors were significant for self (2.13, SE=0.45, P < .001), partner (5.08, SE=0.59, P < .001), and self plus partner (7.04, SE=0.83, P < .001) CFI total scores. At month 48, APOE epsilon 4 carriers had greater progression than noncarriers on the partner (1.10, SE=0.44, P < .012) and self plus partner (1.56, SE=0.63, P < .014) CFI scores. Both self and partner CFI change were associated with longitudinal cognitive decline (self, rho=0.32, 95% CI, 0.13 to 0.46; partner, rho=0.56, 95% CI, 0.42 to 0.68), although findings suggest self-reportmay be more accurate early in the process, whereas accuracy of partner report improves when there is progression to cognitive impairment. CONCLUSIONS AND RELEVANCE Demonstrating long-term clinical benefit will be critical for the success of recently launched secondary prevention trials. The CFI appears to be a brief, but informative potential outcome measure that provides insight into functional abilities at the earliest stages of disease. C1 [Amariglio, Rebecca E.; Marshall, Gad A.; Rentz, Dorene M.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Amariglio, Rebecca E.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Amariglio, Rebecca E.] Harvard Univ, Sch Med, Boston, MA USA. [Donohue, Michael C.] Univ Calif San Diego, Dept Family & Prevent Med, Div Biostat & Bioinformat, San Diego, CA 92103 USA. [Donohue, Michael C.; Salmon, David P.; Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, Alzheimers Dis Cooperat Study, San Diego, CA 92103 USA. [Ferris, Steven H.; Karantzoulis, Stella] NYU, Langone Med Ctr, Ctr Cognit Neurol, Alzheimers Dis Ctr, New York, NY USA. RP Amariglio, RE (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 221 Longwood Ave, Boston, MA 02115 USA. EM ramariglio@partners.org OI Ferris, Steven/0000-0001-8641-6223 FU Alzheimer's Association [NIRG-12-243012]; National Institutes of Health [U19 AG10483, K24 AG035007, P01 AG036694, K23AG044431] FX This study was supported by grant NIRG-12-243012 from the Alzheimer's Association (Dr Amariglio) and grants U19 AG10483 (Dr Aisen), K24 AG035007 (Dr Sperling), P01 AG036694 (Dr Sperling), and K23AG044431 (Dr Amariglio) from the National Institutes of Health. NR 31 TC 13 Z9 13 U1 3 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2015 VL 72 IS 4 BP 446 EP 454 DI 10.1001/jamaneurol.2014.3375 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CH9KG UT WOS:000354353900013 PM 25706191 ER PT J AU Chumbler, NR Li, XL Quigley, P Morey, MC Rose, D Griffiths, P Sanford, J Hoenig, H AF Chumbler, Neale R. Li, Xinli Quigley, Patricia Morey, Miriam C. Rose, Dorian Griffiths, Patricia Sanford, Jon Hoenig, Helen TI A randomized controlled trial on Stroke telerehabilitation: The effects on falls self-efficacy and satisfaction with care SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article DE Telemedicine; stroke; rehabilitation; satisfaction; falls; self-efficacy ID REHABILITATION; SINGAPORE; VETERANS; OUTCOMES AB We determined the effect of a multifaceted stroke telerehabilitation (STeleR) intervention on falls-related self-efficacy and satisfaction with care. We conducted a prospective, randomized, multisite, single-blinded trial in 52 veterans from three Veterans Affairs Medical Centers. Participants who experienced a stroke in the past 24 months were randomized to the STeleR intervention or usual care. Participants in the intervention arm were administered an exit interview to gather specific patient satisfaction data three months after their final outcome measure. The STeleR intervention consisted of three home visits, five telephone calls, and an in-home messaging device provided over three months to instruct patients in functionally based exercises and adaptive strategies. The outcome measures included Falls Efficacy Scale to measure fall-related self-efficacy and a Stroke-Specific Patient Satisfaction with Care (SSPSC) scale, a measure separated into two subscales (satisfaction with home care and satisfaction with hospital care) was employed to measure the participants' satisfaction. At six months, compared with the usual care group, the STeleR group showed statistically significant improvements in one of the two SSPSC scales (satisfaction with hospital care, p = .029) and approached significance in the second SSPSC scale (satisfaction with home care, p = .077). There were no improvements in fall-related self-efficacy. Core concepts identified were: (a) beneficial impact of the trained assistant; (b) exercises helpful; (c) home use of technology. The STeleR intervention improved satisfaction with care, especially as it relates to care following their experience from the hospital. With the limited resources available for in-home rehabilitation for stroke survivors, STeleR (and especially its exercise components) can be a useful complement to traditional post-stroke rehabilitation. C1 [Chumbler, Neale R.] Univ Georgia, Coll Publ Hlth, Dept Hlth Policy & Management, Athens, GA 30602 USA. [Li, Xinli] US Dept Vet Affairs, Natl Surg Off, Deputy Undersecretary Hlth & Operat & Management, Denver, CO USA. [Quigley, Patricia] HSR&D RRD Ctr Excellence, Maximizing Rehabil Outcomes, Tampa, FL USA. [Morey, Miriam C.] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Morey, Miriam C.] Duke Univ, Sch Med, Older Amer Independence Pepper Ctr, Durham, NC USA. [Rose, Dorian] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Phys Therapy, Gainesville, FL USA. [Griffiths, Patricia; Sanford, Jon] Ctr Visual & Neurocognit Rehabil, Atlanta Dept Vet Affairs RR&D, Atlanta, GA USA. [Griffiths, Patricia] GRECC, Dept Vet Affairs Birmingham Atlanta, Atlanta, GA USA. [Griffiths, Patricia] Emory Univ, Sch Med, Div Gen Med & Geriatr, Atlanta, GA 30322 USA. [Sanford, Jon] Georgia Tech Univ, Coll Architecture, Ctr Assist Technol & Environm Access, Atlanta, GA USA. [Hoenig, Helen] Duke Univ, Med Ctr, Durham, NC USA. [Hoenig, Helen] Durham VA Med Ctr, Phys Med & Rehabil Serv, Durham, NC USA. RP Chumbler, NR (reprint author), Univ Georgia, Coll Publ Hlth, Dept Hlth Policy & Management, Athens, GA 30602 USA. EM chumbler@uga.edu FU Department of Veterans Affairs Rehabilitation Research and Development (RRD) [B4492R] FX This research was supported by a grant from the Department of Veterans Affairs Rehabilitation Research and Development (RR&D) (B4492R). An earlier version of this paper was presented at the 2014 International Conference on Collaboration Technologies and Systems in Minneapolis, MN. The opinions contained in this paper are those of the authors and do not necessarily reflect those of the US Department of Veterans Affairs. NR 18 TC 0 Z9 0 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1357-633X EI 1758-1109 J9 J TELEMED TELECARE JI J. Telemed. Telecare PD APR PY 2015 VL 21 IS 3 BP 139 EP 143 DI 10.1177/1357633X15571995 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CI1UL UT WOS:000354530300003 PM 25680390 ER PT J AU Lin, WC Watanabe, H Peng, SY Francis, JM Kaplan, N Pedamallu, CS Ramachandran, A Agoston, A Bass, AJ Meyerson, M AF Lin, Wenchu Watanabe, Hideo Peng, Shouyong Francis, Joshua M. Kaplan, Nathan Pedamallu, Chandra Sekhar Ramachandran, Aruna Agoston, Agoston Bass, Adam J. Meyerson, Matthew TI Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation SO MOLECULAR CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; GENE-EXPRESSION; SUPPRESSOR PROTEIN; TRANSCRIPTION; GROWTH; CHIP; DEMETHYLASE; TYPE-1; FAMILY AB The tumor suppressor gene MEN1 is frequently mutated in sporadic pancreatic neuroendocrine tumors (PanNET) and is responsible for the familial multiple endocrine neoplasia type 1 (MEN-1) cancer syndrome. Menin, the protein product of MEN1, associates with the histone methyltransferases (HMT) MLL1 (KMT2A) and MLL4 (KMT2B) to form menin-HMT complexes in both human and mouse model systems. To elucidate the role of methylation of histone H3 at lysine 4 (H3K4) mediated by menin-HMT complexes during PanNET formation, genome-wide histone H3 lysine 4 trimethylation (H3K4me3) signals were mapped in pancreatic islets using unbiased chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq). Integrative analysis of gene expression profiles and histone H3K4me3 levels identified a number of transcripts and target genes dependent on menin. In the absence of Men1, histone H3K27me3 levels are enriched, with a concomitant decrease in H3K4me3 within the promoters of these target genes. In particular, expression of the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) gene is subject to dynamic epigenetic regulation by Men1-dependent histone modification in a time-dependent manner. Decreased expression of IGF2BP2 in Men1-deficient hyperplastic pancreatic islets is partially reversed by ablation of RBP2 (KDM5A), a histone H3K4-specific demethylase of the jumonji, AT-rich interactive domain 1 (JARID1) family. Taken together, these data demonstrate that loss of Men1 in pancreatic islet cells alters the epigenetic landscape of its target genes. Implications: Epigenetic profiling and gene expression analysis in Men1-deficient pancreatic islet cells reveals vital insight into the molecular events that occur during the progression of pancreatic islet tumorigenesis. C1 [Lin, Wenchu; Watanabe, Hideo; Peng, Shouyong; Francis, Joshua M.; Kaplan, Nathan; Pedamallu, Chandra Sekhar; Ramachandran, Aruna; Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Med Oncol, Boston, MA 02215 USA. [Lin, Wenchu; Watanabe, Hideo; Peng, Shouyong; Francis, Joshua M.; Kaplan, Nathan; Pedamallu, Chandra Sekhar; Ramachandran, Aruna; Agoston, Agoston; Bass, Adam J.; Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lin, Wenchu; Watanabe, Hideo; Peng, Shouyong; Francis, Joshua M.; Kaplan, Nathan; Pedamallu, Chandra Sekhar; Ramachandran, Aruna; Agoston, Agoston; Bass, Adam J.; Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Wenchu; Watanabe, Hideo; Peng, Shouyong; Francis, Joshua M.; Kaplan, Nathan; Pedamallu, Chandra Sekhar; Ramachandran, Aruna; Bass, Adam J.; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc program, Cambridge, MA USA. [Lin, Wenchu] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM matthew_meyerson@dfci.harvard.edu NR 44 TC 7 Z9 8 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2015 VL 13 IS 4 BP 689 EP 698 DI 10.1158/1541-7786.MCR-14-0457 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI5PY UT WOS:000354812000010 PM 25537453 ER PT J AU Liu, Q Wang, M Kern, AM Khaled, S Han, J Yeap, BY Hong, TS Settleman, J Benes, CH Held, KD Efstathiou, JA Willers, H AF Liu, Qi Wang, Meng Kern, Ashley M. Khaled, Saman Han, Jing Yeap, Beow Y. Hong, Theodore S. Settleman, Jeff Benes, Cyril H. Held, Kathryn D. Efstathiou, Jason A. Willers, Henning TI Adapting a Drug Screening Platform to Discover Associations of Molecular Targeted Radiosensitizers with Genomic Biomarkers SO MOLECULAR CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; ANTICANCER AGENTS; PROGNOSTIC-FACTOR; KINASE INHIBITOR; STEM-CELLS; RADIATION; RADIOTHERAPY; SENSITIVITY; LINES; EGFR AB Large collections of annotated cancer cell lines are powerful tools for precisely matching targeted drugs with genomic alterations that can be tested as biomarkers in the clinic. Whether these screening platforms, which utilize short-term cell survival to assess drug responses, can be applied to precision radiation medicine is not established. To this end, 32 cancer cell lines were screened using 18 targeted therapeutic agents with known or putative radiosensitizing properties (227 combinations). The cell number remaining after drug exposure with or without radiation was assessed by nonclonogenic assays. We derived short-term radiosensitization factors (SRF2Gy) and calculated clonogenic survival assay-based dose enhancement factors (DEFSF0.1). Radiosensitization was characterized by SRF2Gy values of mostly similar to 1.05 to 1.2 and significantly correlated with drug-induced changes in apoptosis and senescence frequencies. SRF2Gy was significantly cor-related with DEFSF0.1, with a respective sensitivity and specificity of 91.7% and 81.5% for a 3-day endpoint, and 82.8% and 84.2% for a robotic 5-day assay. KRAS mutations (codons 12/13) were found to be a biomarker of radiosensitization by midostaurin in lung cancer, which was pronounced under conditions that enriched for stem cell-like cells. In conclusion, although short-term proliferation/survival assays cannot replace the gold-standard clonogenic survival assay for measuring cellular radiosensitivity, they capture with high accuracy the relative change in radiosensitivity that is caused by a radiosensitzing targeted agent. Implications: This study supports a paradigm shift regarding the utility of short-term assays for precision radiation medicine, which should facilitate the identification of genomic biomarkers to guide the testing of novel drug/radiation combinations. C1 [Liu, Qi; Wang, Meng; Kern, Ashley M.; Khaled, Saman; Han, Jing; Held, Kathryn D.; Efstathiou, Jason A.; Willers, Henning] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Cellular & Mol Radiat Oncol,Ctr Canc, Charlestown, MA USA. [Liu, Qi; Wang, Meng; Kern, Ashley M.; Khaled, Saman; Han, Jing; Hong, Theodore S.; Held, Kathryn D.; Efstathiou, Jason A.; Willers, Henning] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Han, Jing] Jinan Municipal Ctr Dis Control & Prevent, Jinan, Shandong, Peoples R China. [Yeap, Beow Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Biostat Unit, Boston, MA USA. [Settleman, Jeff; Benes, Cyril H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res,Ctr Canc, Charlestown, MA USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM hwillers@mgh.harvard.edu FU Dana-Farber/Harvard Cancer Center Specialized Program Of Research Excellence in Lung Cancer [P50 CA090578]; American Cancer Society [123420RSG-12-224-01-DMC]; UK Wellcome Trust [086357]; Jinan Municipal Center for Disease Control and Prevention, Shandong, China; Federal Share of program income [C06 CA059267] FX This work was supported by the Dana-Farber/Harvard Cancer Center Specialized Program Of Research Excellence in Lung Cancer (P50 CA090578, to B.Y. Yeap, J. Settleman, and H. Willers); American Cancer Society (123420RSG-12-224-01-DMC, to H. Willers); UK Wellcome Trust (086357, to J. Settleman and C.H. Benes); a stipend from the Jinan Municipal Center for Disease Control and Prevention, Shandong, China (to J. Han); and Federal Share of program income earned by Massachusetts General Hospital, Proton Therapy Research and Treatment Center (C06 CA059267, to B.Y. Yeap, J. A. Efstathiou, K.D. Held, and H. Willers). NR 50 TC 3 Z9 3 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2015 VL 13 IS 4 BP 713 EP 720 DI 10.1158/1541-7786.MCR-14-0570 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI5PY UT WOS:000354812000012 PM 25667133 ER PT J AU Kim, Y Apetri, M Luo, BB Settleman, JE Anderson, KS AF Kim, Youngjoo Apetri, Mihaela Luo, BeiBei Settleman, Jeffrey E. Anderson, Karen S. TI Differential Effects of Tyrosine Kinase Inhibitors on Normal and Oncogenic EGFR Signaling and Downstream Effectors SO MOLECULAR CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; FACTOR-RECEPTOR; C-SRC; CONSTITUTIVE ACTIVATION; IN-VIVO; GEFITINIB; MUTATIONS; PHOSPHORYLATION; MUTANTS AB Constitutive activation of EGFR due to overexpression or mutation in tumor cells leads to dysregulated downstream cellular signaling pathways. Therefore, EGFR as well as its downstream effectors have been identified as important therapeutic targets. The FDA-approved small-molecule inhibitors of EGFR, gefitinib (Iressa) and erlotinib (Tarceva), are clinically effective in a subset of patients with non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations within the kinase domain of EGFR. The current study examined effects of these drugs in 32D cells expressing native (WT) or oncogenic (L858R) EGFR as well as in cancer cell lines A431 and H3255. Distinct patterns for gefitinib and erlotinib inhibition of EGFR autophosphorylation at individual tyrosines were revealed for wild-type (WT) and L858R EGFR. Phosphorylation of Y845 has been shown to be important in cancer cells and Y1045 phosphorylation is linked to Cbl-mediated ubiquitination and degradation. Dramatic differences were observed by greater potency of these drugs for inhibiting downstream effectors for L858R EGFR including Cbl and STAT5. Selective targeting of Cbl may play a role in oncogene addiction and effects on STAT5 identify features of signaling circuitry for L858R EGFR that contribute to drug sensitivity and clinical efficacy. These data provide new understanding of the EGFR signaling environment and suggest useful paradigms for predicting patient response to EGFR-targeted therapy as well as combination treatments. Implications: This study offers fundamental insights for understanding molecular mechanisms of drug sensitivity on oncogenic forms of EGFR and downstream signaling components as well as considerations for further drug optimization and design of combination therapy. C1 [Kim, Youngjoo; Apetri, Mihaela; Luo, BeiBei; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Settleman, Jeffrey E.] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. [Settleman, Jeffrey E.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Anderson, KS (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. EM karen.anderson@yale.edu FU National Institute of Health [NCI CA127580, CA125284] FX This research was supported by National Institute of Health grants NCI CA127580 and CA125284 to K.S. Anderson. NR 51 TC 2 Z9 2 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2015 VL 13 IS 4 BP 765 EP 774 DI 10.1158/1541-7786.MCR-14-0326 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI5PY UT WOS:000354812000017 PM 25573954 ER PT J AU Schiff, D Lee, EQ Nayak, L Norden, AD Reardon, DA Wen, PY AF Schiff, David Lee, Eudocia Q. Nayak, Lakshmi Norden, Andrew D. Reardon, David A. Wen, Patrick Y. TI Medical management of brain tumors and the sequelae of treatment SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab; brain tumor; chemotherapy; cognition; complications; corticosteroids; fatigue; mood; seizure; symptom management; vasogenic edema; venous thromboembolism ID NEWLY-DIAGNOSED GLIOBLASTOMA; RECURRENT MALIGNANT GLIOMA; PLACEBO-CONTROLLED TRIAL; HIGH-GRADE GLIOMAS; QUALITY-OF-LIFE; PNEUMOCYSTIS-CARINII-PNEUMONIA; INDUCED COGNITIVE IMPAIRMENT; CLINICAL-PRACTICE GUIDELINE; RANDOMIZED CONTROLLED-TRIAL; NERVOUS-SYSTEM METASTASES AB Patients with malignant brain tumors are prone to complications that negatively impact their quality of life and sometimes their overall survival as well. Tumors may directly provoke seizures, hypercoagulable states with resultant venous thromboembolism, and mood and cognitive disorders. Antitumor treatments and supportive therapies also produce side effects. In this review, we discuss major aspects of supportive care for patients with malignant brain tumors, with particular attention to management of seizures, venous thromboembolism, corticosteroids and their complications, chemotherapy including bevacizumab, and fatigue, mood, and cognitive dysfunction. C1 [Schiff, David] Univ Virginia, Med Ctr, Neurooncol Ctr, Charlottesville, VA USA. [Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Reardon, David A.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Reardon, David A.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Schiff, D (reprint author), Hosp West, Neurooncol Ctr, Room 6225,Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM ds4jd@virginia.edu FU Merck FX David A. Reardon is on speaker 'bureaus for Roche/Genentech and Merck/Schering and advisory boards for Amgen, Novartis, Momenta, Stemline, EMD Serono, Merck/Schering, Roche/Genentech, and Midatech. David Schiff has received research support from Merck and has served on advisory boards for Genentech and Sigma Tau. Lakshmi Nayak is on an advisory board for Amgen. The other authors have nothing to disclose regarding this work. NR 209 TC 13 Z9 13 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2015 VL 17 IS 4 BP 488 EP 504 DI 10.1093/neuonc/nou304 PG 17 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI4KT UT WOS:000354718200003 PM 25358508 ER PT J AU Kharasch, SJ AF Kharasch, Sigmund J. TI A Slice of Peace SO PEDIATRICS LA English DT Editorial Material C1 [Kharasch, Sigmund J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kharasch, SJ (reprint author), Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM skharasch@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2015 VL 135 IS 4 BP 592 EP 593 DI 10.1542/peds.2014-3014 PG 2 WC Pediatrics SC Pediatrics GA CH0QG UT WOS:000353726700045 PM 25733750 ER PT J AU Van Cleave, J AF Van Cleave, Jeanne TI Children With Special Health Care Needs: With Population-Based Data, Better Individual Care Plans SO PEDIATRICS LA English DT Article ID NATIONAL PROFILE C1 [Van Cleave, Jeanne] MassGen Hosp Children, Div Gen Acad Pediat, Boston, MA USA. [Van Cleave, Jeanne] Harvard Univ, Sch Med, Boston, MA USA. RP Van Cleave, J (reprint author), 100 Cambridge St,15th Floor,C100, Boston, MA 02114 USA. EM jvancleave@partners.org NR 14 TC 0 Z9 0 U1 3 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2015 VL 135 IS 4 BP E1040 EP E1041 DI 10.1542/peds.2015-0319 PG 2 WC Pediatrics SC Pediatrics GA CH0QG UT WOS:000353726700028 PM 25780065 ER PT J AU Choi, I Chung, AW Suscovich, TJ Rerks-Ngarm, S Pitisuttithum, P Nitayaphan, S Kaewkungwal, J O'Connell, RJ Francis, D Robb, ML Michael, NL Kim, JH Alter, G Ackerman, ME Bailey-Kellogg, C AF Choi, Ickwon Chung, Amy W. Suscovich, Todd J. Rerks-Ngarm, Supachai Pitisuttithum, Punnee Nitayaphan, Sorachai Kaewkungwal, Jaranit O'Connell, Robert J. Francis, Donald Robb, Merlin L. Michael, Nelson L. Kim, Jerome H. Alter, Galit Ackerman, Margaret E. Bailey-Kellogg, Chris TI Machine Learning Methods Enable Predictive Modeling of Antibody Feature: Function Relationships in RV144 Vaccinees SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; HIV-1/SIV CHIMERIC VIRUS; NEUTRALIZING ANTIBODIES; DISEASE PROGRESSION; HIGH-THROUGHPUT; EFFICACY TRIAL; REGRESSION; INFECTION; VACCINATION; PROTECTION AB The adaptive immune response to vaccination or infection can lead to the production of specific antibodies to neutralize the pathogen or recruit innate immune effector cells for help. The non-neutralizing role of antibodies in stimulating effector cell responses may have been a key mechanism of the protection observed in the RV144 HIV vaccine trial. In an extensive investigation of a rich set of data collected from RV144 vaccine recipients, we here employ machine learning methods to identify and model associations between antibody features (IgG subclass and antigen specificity) and effector function activities (antibody dependent cellular phagocytosis, cellular cytotoxicity, and cytokine release). We demonstrate via cross-validation that classification and regression approaches can effectively use the antibody features to robustly predict qualitative and quantitative functional outcomes. This integration of antibody feature and function data within a machine learning framework provides a new, objective approach to discovering and assessing multivariate immune correlates. C1 [Choi, Ickwon; Bailey-Kellogg, Chris] Dartmouth Coll, Dept Comp Sci, Hanover, NH 03755 USA. [Chung, Amy W.; Suscovich, Todd J.; Alter, Galit] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Chung, Amy W.; Suscovich, Todd J.; Alter, Galit] Harvard, Boston, MA USA. [Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand. [Pitisuttithum, Punnee; Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Bangkok, Thailand. [Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. [O'Connell, Robert J.] AFRIMS, US Army Med Component, Dept Retrovirol, Bangkok, Thailand. [Francis, Donald] Global Solut Infect Dis GSID, San Francisco, CA USA. [Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Robb, Merlin L.] US Mil HIV Res Program, Henry Jackson Fdn HIV Program, Bethesda, MD USA. [Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Choi, I (reprint author), Dartmouth Coll, Dept Comp Sci, Hanover, NH 03755 USA. EM cbk@cs.dartmouth.edu OI Chung, Amy/0000-0003-0020-9704 FU US Military HIV Research Program (MHRP); Collaboration for AIDS Vaccine Discovery [OPP1032817]; NSF [IIS-0905206]; American Australian Association; National Health & Medical Research Center [NHMRC APP1036470]; U.S. Army Medical Research and Material Command (USAMRMC) [Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases [Y1-AI-2642-12]; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense [W81XWH-07-2-0067]; [NIH3R01Al080289-02S1]; [5R01Al080289-03] FX These studies were supported by the US Military HIV Research Program (MHRP), the Collaboration for AIDS Vaccine Discovery (OPP1032817: Leveraging Antibody Effector Function) to MEA, GA, and CBK, and NIH3R01Al080289-02S1 and 5R01Al080289-03 to GA. IC was supported by NSF grant IIS-0905206. AWC was supported by the American Australian Association (Amgen Fellowship) and National Health & Medical Research Center (NHMRC APP1036470). The work was also supported in part by an Interagency Agreement Y1-AI-2642-12 between the U.S. Army Medical Research and Material Command (USAMRMC) and the National Institutes of Allergy and Infectious Diseases and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 4 Z9 4 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2015 VL 11 IS 4 AR UNSP e1004185 DI 10.1371/journal.pcbi.1004185 PG 20 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CI1PX UT WOS:000354517600034 PM 25874406 ER PT J AU Ghiassian, SD Menche, J Barabasi, AL AF Ghiassian, Susan Dina Menche, Joerg Barabasi, Albert-Laszlo TI A DIseAse MOdule Detection (DIAMOnD) Algorithm Derived from a Systematic Analysis of Connectivity Patterns of Disease Proteins in the Human Interactome SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PROTEOME-SCALE MAP; INTERACTION NETWORK; COMPREHENSIVE RESOURCE; RANDOM-WALKS; COVER TIME; GENES; MEDICINE; GENOME; PROFILES; GRAPHS AB The observation that disease associated proteins often interact with each other has fueled the development of network-based approaches to elucidate the molecular mechanisms of human disease. Such approaches build on the assumption that protein interaction networks can be viewed as maps in which diseases can be identified with localized perturbation within a certain neighborhood. The identification of these neighborhoods, or disease modules, is therefore a prerequisite of a detailed investigation of a particular pathophenotype. While numerous heuristic methods exist that successfully pinpoint disease associated modules, the basic underlying connectivity patterns remain largely unexplored. In this work we aim to fill this gap by analyzing the network properties of a comprehensive corpus of 70 complex diseases. We find that disease associated proteins do not reside within locally dense communities and instead identify connectivity significance as the most predictive quantity. This quantity inspires the design of a novel Disease Module Detection (DIAMOnD) algorithm to identify the full disease module around a set of known disease proteins. We study the performance of the algorithm using well-controlled synthetic data and systematically validate the identified neighborhoods for a large corpus of diseases. C1 [Ghiassian, Susan Dina; Menche, Joerg; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Ghiassian, Susan Dina; Menche, Joerg; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Ghiassian, Susan Dina; Menche, Joerg; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02115 USA. [Ghiassian, Susan Dina; Menche, Joerg; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Menche, Joerg; Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, Budapest, Hungary. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Dept Med,Med Sch, Boston, MA 02115 USA. RP Ghiassian, SD (reprint author), Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. EM barabasi@gmail.com RI Menche, Jorg/G-3994-2015 OI Menche, Jorg/0000-0002-1583-6404 FU National Institutes of Health (NIH) [1U01HL108630-01] FX This work was funded by National Institutes of Health (NIH) Award #1U01HL108630-01. MAPGen (http://www.mapgenprogram.org/) and NIH, Centers of Excellence of Genomic Science (CEGS), NIH CEGS 1P50HG004233 (http://www.genome.gov/10001771). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 14 Z9 14 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2015 VL 11 IS 4 AR e1004120 DI 10.1371/journal.pcbi.1004120 PG 21 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CI1PX UT WOS:000354517600010 PM 25853560 ER PT J AU Wager, TD Kang, J Johnson, TD Nichols, TE Satpute, AB Barrett, LF AF Wager, Tor D. Kang, Jian Johnson, Timothy D. Nichols, Thomas E. Satpute, Ajay B. Barrett, Lisa Feldman TI A Bayesian Model of Category-Specific Emotional Brain Responses SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID INTRINSIC FUNCTIONAL CONNECTIVITY; MAJOR DEPRESSIVE DISORDER; MEDIAL PREFRONTAL CORTEX; NONNEGATIVE MATRIX FACTORIZATION; COGNITIVE-AFFECTIVE SYNDROME; PATTERN-CLASSIFICATION; DEFAULT-MODE; CARDIOVASCULAR-RESPONSES; PHYSIOLOGICAL CONDITION; NEUROIMAGING DATA AB Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories-fear, anger, disgust, sadness, or happiness-is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. C1 [Wager, Tor D.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Wager, Tor D.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA. [Kang, Jian] Emory Univ, Dept Radiol & Imaging Sci, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Johnson, Timothy D.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Oxford, Nuffield Dept Clin Neurosci, Funct Magnet Resonance Imaging Brain FMRIB Ctr, Oxford, England. [Satpute, Ajay B.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Wager, TD (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. EM tor.wager@colorado.edu OI Satpute, Ajay/0000-0003-0227-0816 FU U.S. Army Research Institute for the Behavioral and Social Sciences [W5J9CQ-11-C-0046]; TDW, a National Institutes of Health Director's Pioneer Award [DP1OD003312, R01MH076136, R01-NS-075066] FX This research was supported by the U.S. Army Research Institute for the Behavioral and Social Sciences (contract W5J9CQ-11-C-0046) [https://sslweb.hqda.pentagon.mil/ari/] to LFB and TDW, a National Institutes of Health Director's Pioneer Award (DP1OD003312) [http://commonfund.nih.gov/pioneer/index] to LFB, R01MH076136 to TDW, and R01-NS-075066 to TDJ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 109 TC 17 Z9 17 U1 13 U2 31 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2015 VL 11 IS 4 AR e1004066 DI 10.1371/journal.pcbi.1004066 PG 27 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CI1PX UT WOS:000354517600003 PM 25853490 ER PT J AU Williamson, RS Sahani, M Pillow, JW AF Williamson, Ross S. Sahani, Maneesh Pillow, Jonathan W. TI The Equivalence of Information-Theoretic and Likelihood-Based Methods for Neural Dimensionality Reduction SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID RECEPTIVE-FIELDS; SPIKING ACTIVITY; MODELS; CORTEX; POPULATION; RESPONSES; CELLS; NONLINEARITIES; COMPUTATION; MOTION AB Stimulus dimensionality-reduction methods in neuroscience seek to identify a low-dimensional space of stimulus features that affect a neuron's probability of spiking. One popular method, known as maximally informative dimensions (MID), uses an information-theoretic quantity known as "single-spike information" to identify this space. Here we examine MID from a model-based perspective. We show that MID is a maximum-likelihood estimator for the parameters of a linear-nonlinear-Poisson (LNP) model, and that the empirical single-spike information corresponds to the normalized log-likelihood under a Poisson model. This equivalence implies that MID does not necessarily find maximally informative stimulus dimensions when spiking is not well described as Poisson. We provide several examples to illustrate this shortcoming, and derive a lower bound on the information lost when spiking is Bernoulli in discrete time bins. To overcome this limitation, we introduce model-based dimensionality reduction methods for neurons with non-Poisson firing statistics, and show that they can be framed equivalently in likelihood-based or information-theoretic terms. Finally, we show how to overcome practical limitations on the number of stimulus dimensions that MID can estimate by constraining the form of the non-parametric nonlinearity in an LNP model. We illustrate these methods with simulations and data from primate visual cortex. C1 [Williamson, Ross S.; Sahani, Maneesh] UCL, Gatsby Computat Neurosci Unit, London, England. [Williamson, Ross S.] UCL, Ctr Math & Phys Life Sci & Expt Biol, London, England. [Pillow, Jonathan W.] Princeton Univ, Dept Psychol, Princeton Neurosci Inst, Princeton, NJ 08544 USA. RP Williamson, RS (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. EM ross_williamson@meei.harvard.edu; pillow@princeton.edu FU Engineering and Physical Sciences Research Council; Gatsby Charitable Foundation; Sloan Fellowship; McKnight Scholar's award; NSF CAREER award [IIS-1150186] FX This work was supported by the Engineering and Physical Sciences Research Council (support for RSW through the CoMPLEX Doctoral Training Program), the Gatsby Charitable Foundation (Gatsby Computational Neuroscience Unit support to RSW and MS) and Sloan Fellowship, McKnight Scholar's award, and NSF CAREER award IIS-1150186 (support to JWP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 6 Z9 6 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2015 VL 11 IS 4 AR e1004141 DI 10.1371/journal.pcbi.1004141 PG 31 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CI1PX UT WOS:000354517600019 PM 25831448 ER PT J AU Moutsianas, L Agarwala, V Fuchsberger, C Flannick, J Rivas, MA Gaulton, KJ Albers, PK McVean, G Boehnke, M Altshuler, D McCarthy, MI AF Moutsianas, Loukas Agarwala, Vineeta Fuchsberger, Christian Flannick, Jason Rivas, Manuel A. Gaulton, Kyle J. Albers, Patrick K. McVean, Gil Boehnke, Michael Altshuler, David McCarthy, Mark I. CA GoT2D Consortium TI The Power of Gene-Based Rare Variant Methods to Detect Disease-Associated Variation and Test Hypotheses About Complex Disease SO PLOS GENETICS LA English DT Article ID STATISTICAL TESTS; CODING VARIANTS; TRAITS; LINKAGE AB Genome and exome sequencing in large cohorts enables characterization of the role of rare variation in complex diseases. Success in this endeavor, however, requires investigators to test a diverse array of genetic hypotheses which differ in the number, frequency and effect sizes of underlying causal variants. In this study, we evaluated the power of gene-based association methods to interrogate such hypotheses, and examined the implications for study design. We developed a flexible simulation approach, using 1000 Genomes data, to (a) generate sequence variation at human genes in up to 10K case-control samples, and (b) quantify the statistical power of a panel of widely used gene-based association tests under a variety of allelic architectures, locus effect sizes, and significance thresholds. For loci explaining similar to 1% of phenotypic variance underlying a common dichotomous trait, we find that all methods have low absolute power to achieve exome-wide significance (similar to 5-20% power at alpha=2.5x10(-6)) in 3K individuals; even in 10K samples, power is modest (similar to 60%). The combined application of multiple methods increases sensitivity, but does so at the expense of a higher false positive rate. MiST, SKAT-O, and KBAC have the highest individual mean power across simulated datasets, but we observe wide architecture-dependent variability in the individual loci detected by each test, suggesting that inferences about disease architecture from analysis of sequencing studies can differ depending on which methods are used. Our results imply that tens of thousands of individuals, extensive functional annotation, or highly targeted hypothesis testing will be required to confidently detect or exclude rare variant signals at complex disease loci. C1 [Moutsianas, Loukas; Rivas, Manuel A.; Gaulton, Kyle J.; Albers, Patrick K.; McVean, Gil; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Agarwala, Vineeta] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Agarwala, Vineeta; Flannick, Jason; Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Fuchsberger, Christian; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Fuchsberger, Christian; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. RP Moutsianas, L (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM moutsian@well.ox.ac.uk; mark.mccarthy@drl.ox.ac.uk RI Hrabe de Angelis, Martin/F-5531-2012; OI Hrabe de Angelis, Martin/0000-0002-7898-2353; Fuchsberger, Christian/0000-0002-5918-8947; Kumar, Ashish/0000-0002-7075-5930 FU Wellcome Trust [090367, 098381, 090532]; National Institutes of Health (NIH) [U01-DK085545, RC2-HG005688, HG000376, DK062370]; Doris Duke Charitable Foundation [2006087]; National Institute of Diabetes and Digestive and Kidney diseases (NIDDK) [R01-DK098032]; NIH [DK062370, T32GM007753, T32GM008313]; FWF [J-3401]; Clarendon Fund of the University of Oxford; Nuffield Department of Medicine; NIDDK [1RC2DK088389] FX This work was supported by grants from the Wellcome Trust (award numbers 090367, 098381, 090532 to MIM), the National Institutes of Health (NIH, awards U01-DK085545 to MIM., RC2-HG005688 to MIM., MB and DA, and HG000376 and DK062370 to MB), the Doris Duke Charitable Foundation (award number 2006087 to DA) and the National Institute of Diabetes and Digestive and Kidney diseases (NIDDK, awards R01-DK098032 to MB, DA, and MIM). VA was supported by NIH Training Grants T32GM007753 and T32GM008313. CF was supported by NIH grant DK062370 and by FWF Grant J-3401. MAR was supported by a scholarship funded by the Clarendon Fund of the University of Oxford, and the Nuffield Department of Medicine. MIM is a Wellcome Trust Senior Investigator. The GoT2D Study was supported by grant 1RC2DK088389 from the NIDDK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 24 Z9 24 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2015 VL 11 IS 4 AR e1005165 DI 10.1371/journal.pgen.1005165 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA CI1SH UT WOS:000354524200049 PM 25906071 ER PT J AU Oltrabella, F Pietka, G Ramirez, IBR Mironov, A Starborg, T Drummond, IA Hinchliffe, KA Lowe, M AF Oltrabella, Francesca Pietka, Grzegorz Ramirez, Irene Barinaga-Rementeria Mironov, Aleksandr Starborg, Toby Drummond, Iain A. Hinchliffe, Katherine A. Lowe, Martin TI The Lowe Syndrome Protein OCRL1 Is Required for Endocytosis in the Zebrafish Pronephric Tubule SO PLOS GENETICS LA English DT Article ID RENAL PROXIMAL TUBULE; TRANS-GOLGI NETWORK; IMPAIRS ENDOCYTOSIS; EPITHELIAL-CELLS; PRIMARY CILIA; IN-VIVO; TRAFFICKING; 5-PHOSPHATASE; BINDING; ACTIN AB Lowe syndrome and Dent-2 disease are caused by mutation of the inositol 5-phosphatase OCRL1. Despite our increased understanding of the cellular functions of OCRL1, the underlying basis for the renal tubulopathy seen in both human disorders, of which a hallmark is low molecular weight proteinuria, is currently unknown. Here, we show that deficiency in OCRL1 causes a defect in endocytosis in the zebrafish pronephric tubule, a model for the mammalian renal tubule. This coincides with a reduction in levels of the scavenger receptor megalin and its accumulation in endocytic compartments, consistent with reduced recycling within the endocytic pathway. We also observe reduced numbers of early endocytic compartments and enlarged vacuolar endosomes in the sub-apical region of pronephric cells. Cell polarity within the pronephric tubule is unaffected in mutant embryos. The OCRL1-deficient embryos exhibit a mild ciliogenesis defect, but this cannot account for the observed impairment of endocytosis. Catalytic activity of OCRL1 is required for renal tubular endocytosis and the endocytic defect can be rescued by suppression of PIP5K. These results indicate for the first time that OCRL1 is required for endocytic trafficking in vivo, and strongly support the hypothesis that endocytic defects are responsible for the renal tubulopathy in Lowe syndrome and Dent-2 disease. Moreover, our results reveal PIP5K as a potential therapeutic target for Lowe syndrome and Dent-2 disease. C1 [Oltrabella, Francesca; Pietka, Grzegorz; Ramirez, Irene Barinaga-Rementeria; Mironov, Aleksandr; Starborg, Toby; Hinchliffe, Katherine A.; Lowe, Martin] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Drummond, Iain A.] Harvard Univ, Dept Genet, Sch Med, Charlestown, MA USA. RP Oltrabella, F (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM martin.lowe@manchester.ac.uk OI Oltrabella, Francesca/0000-0003-0353-8968 FU Wellcome Trust [079615]; UK Lowe Syndrome Trust [ML/MU/DEC07, NoMU/ML/1010] FX This work was funded by a Wellcome Trust project grant (079615) and research grants from the UK Lowe Syndrome Trust awarded to ML (ML/MU/DEC07 and NoMU/ML/1010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 13 Z9 13 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2015 VL 11 IS 4 AR e1005058 DI 10.1371/journal.pgen.1005058 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA CI1SH UT WOS:000354524200006 PM 25838181 ER PT J AU Carter, A Nicholas, M Hunsaker, E Jacobson, AM AF Carter, Alina Nicholas, Marjorie Hunsaker, Eileen Jacobson, Anne McCarthy TI Modified Berg Balance Scale: making assessment appropriate for people with aphasia SO TOPICS IN STROKE REHABILITATION LA English DT Article DE Aphasia; Berg Balance Scale; Healthcare assessment; Auditory comprehension; Speech therapy; Physical therapy ID STROKE; ADULTS AB Objective: Modifying assessments for people with aphasia has the potential to increase the validity of healthcare assessments across professional domains. This pilot study addressed the challenges of giving people with aphasia the power to fully participate in the assessment process. The study aimed to investigate the feasibility of using an aphasia-modified version of the Berg Balance Scale (BBS), a physical therapy assessment tool to quantify dynamic sitting and standing balance. Method: The study compared how people with aphasia performed on the original BBS to an aphasia-modified version (MBBS), created for this study. We examined the relationship between auditory comprehension scores and balance performance of 15 participants with chronic aphasia and three control participants. We tested the hypothesis that individuals with aphasia would perform higher on the MBBS rather than the BBS, thus more closely approaching a score reflective of their true physical abilities. Results: Overall people with aphasia performed significantly better on the MBBS than the BBS, indicating that at least some portion of their performance difficulty was likely due to poor auditory comprehension of test instructions rather than true balance difficulty. Conclusion: Implications of this study suggest that modifying assessments, such as the BBS, by reducing linguistic complexity and adding visual and written cues along with modeling and repetition has the potential to increase the validity of healthcare assessments for individuals with aphasia. C1 [Carter, Alina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carter, Alina; Nicholas, Marjorie; Hunsaker, Eileen; Jacobson, Anne McCarthy] MGH Inst Hlth Profess, Boston, MA USA. [Hunsaker, Eileen; Jacobson, Anne McCarthy] Spaulding Rehabil Network, Boston, MA USA. RP Carter, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carter.alina@gmail.com NR 16 TC 0 Z9 0 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1074-9357 EI 1945-5119 J9 TOP STROKE REHABIL JI Top. Stroke Rehabil. PD APR PY 2015 VL 22 IS 2 BP 83 EP 93 DI 10.1179/1074935714Z.0000000034 PG 11 WC Rehabilitation SC Rehabilitation GA CI8IJ UT WOS:000355015700001 PM 25936540 ER PT J AU Friedman, LS AF Friedman, Lawrence S. TI GRG Profiles: Lawrence S. Friedman SO DIGESTIVE DISEASES AND SCIENCES LA English DT Biographical-Item ID MULTISOCIETY TASK-FORCE; 5-AMINOSALICYLIC ACID ENEMAS; ULCERATIVE-COLITIS; DISEASE C1 [Friedman, Lawrence S.] Harvard Univ, Sch Med, Boston, MA USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2015 VL 60 IS 4 BP 827 EP 831 DI 10.1007/s10620-015-3599-7 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI0YC UT WOS:000354464900008 PM 25732716 ER PT J AU Friedman, LS AF Friedman, Lawrence S. TI Teaching in the Office SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID ELECTRONIC HEALTH RECORD C1 [Friedman, Lawrence S.] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. EM lfriedman@partners.org NR 11 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2015 VL 60 IS 4 BP 832 EP 834 DI 10.1007/s10620-015-3623-y PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI0YC UT WOS:000354464900009 PM 25764499 ER PT J AU Akiba, Y Kaunitz, JD Million, M AF Akiba, Yasutada Kaunitz, Jonathan D. Million, Mulugeta TI Peripheral Corticotropin-Releasing Factor Receptor Type 2 Activation Increases Colonic Blood Flow Through Nitric Oxide Pathway in Rats SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Colonic blood flow; Corticotropin-releasing factor; Mouse urocortin 2; Sauvagine; Astressin(2)-B; Nitric oxide ID STRESS-RELATED ALTERATIONS; ACID-SENSING PATHWAYS; FACTOR CRF FAMILY; UROTENSIN-I; PROSTAGLANDIN E-2; GASTRIC TRANSIT; SENSORY NEURONS; MUCOSAL DEFENSE; MOTOR FUNCTION; UROCORTIN-II AB Background Corticotropin-releasing factor (CRF) peptides exert profound effects on the secretomotor function of the gastrointestinal tract. Nevertheless, despite the presence of CRF peptides and receptors in colonic tissue, their influence on colonic blood flow (CBF) is unknown. Aim To determine the effect and mechanism of members of the CRF peptide family on CBF in isoflurane-anesthetized rats. Methods Proximal CBF was measured with laser-Doppler flowmetry simultaneously with mean arterial blood pressure (MABP) measurement. Rats were injected with intravenous human/rat CRF (CRF1 > CRF2 affinity), mouse urocortin 2 (mUcn2, selective CRF2 agonist), or sauvagine (SVG, CRF2 > CRF1 affinity) at 1-30 mu g/kg. The nitric oxide (NO) synthase inhibitor, L-NAME (3 mg/kg, iv), the cyclooxygenase inhibitor, indomethacin (Indo, 5 mg/kg, ip), or selective CRF2 antagonist, astressin(2)-B (Ast(2)B, 50 mu g/kg, iv) was given before SVG injection (10 mu g/kg, iv). Results SVG and mUcn2 dose-dependently increased CBF while decreasing MABP and colonic vascular resistance (CVR). CRF had no effect on CBF, but increased CVR. The hyperemic effect of SVG was inhibited by L-NAME but not by Indo, whereas hypotension was partially reduced by L-NAME. Sensory denervation had no effect on SVG-induced changes. Ast(2)B inhibited SVG-induced hyperemia and decreased CVR, and partially reduced the hypotension. Conclusions Peripheral CRF2 activation induces colonic hyperemia through NO synthesis, without involving prostaglandin synthesis or sensory nerve activation, suggesting a direct action on the endothelium and myenteric neurons. Members of the CRF peptide family may protect the colonic mucosa via the activation of the CRF2 receptor. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.; Million, Mulugeta] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Family Ctr Neurobiol Stress, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] VA Greater Los Angles Healthcare Syst, Los Angeles, CA 90073 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Million, Mulugeta] VA Greater Los Angles Healthcare Syst, Los Angeles, CA 90073 USA. RP Million, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Family Ctr Neurobiol Stress, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. EM yakiba@mednet.ucla.edu; jake@ucla.edu; mmuluget@ucla.edu FU NIHDDK [DK 57238-01A1S1, DK078676]; Department of Veterans Affairs Merit Review Award; NIH-NIDDK [RO1 DK54221]; [NIHDDK-41303] FX We would like to thank Dr. Yvette Tache (UCLA) and Dr. Jean Rivier (Salk Institute, Peptide Laboratories) for their suggestions and peptide supply. Authors received study support from NIHDDK-41303 Animal Model Core (MM, JDK), NIHDDK DK 57238-01A1S1 & DK078676 (MM), Department of Veterans Affairs Merit Review Award, and NIH-NIDDK RO1 DK54221 (JDK). NR 55 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2015 VL 60 IS 4 BP 858 EP 867 DI 10.1007/s10620-015-3579-y PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CI0YC UT WOS:000354464900014 PM 25701320 ER PT J AU Hernandez, R Kershaw, KN Prohaska, TR Wang, PC Marquez, DX Sarkisian, CA AF Hernandez, Rosalba Kershaw, Kiarri N. Prohaska, Thomas R. Wang, Pin-Chieh Marquez, David X. Sarkisian, Catherine A. TI The Cross-Sectional and Longitudinal Association Between Perceived Neighborhood Walkability Characteristics and Depressive Symptoms in Older Latinos: The "!Caminemos!" Study SO JOURNAL OF AGING AND HEALTH LA English DT Article DE older adults; Hispanics/Latinos; depressive symptoms; neighborhood/environment ID MENTAL-HEALTH-CARE; ETHNIC DISPARITIES; SOCIAL SUPPORT; 5-ITEM VERSION; ADULTS; SCALE; PREVALENCE; COMMUNITY; ENVIRONMENT; POPULATION AB Objective: Evaluate the cross-sectional and longitudinal association between perceived walkability-related neighborhood characteristics (e.g., traffic safety) and depressive symptoms among community-dwelling older Latino adults. Method: We used baseline, 12-month, and 24-month in-person interview data collected from Latinos aged >= 60 years participating in an exercise intervention at 27 senior centers (N = 570). Results: In cross-sectional analyses, lower perceived neighborhood crime, indicative of greater neighborhood walkability, was associated with a lower odds of elevated symptoms of depression (odds ratio [OR] = 0.90; 95% confidence interval [CI] = [0.82, 0.996]; p = .04) after adjusting for demographic characteristics, linguistic acculturation, and medical comorbidities. Associations between Neighborhood Environment Walkability scales and incident depressive symptoms at 12- and/or 24-months were not statistically significant, but the point estimate for crime safety was consistent with cross-sectional findings (OR = 0.83; 95% CI = [0.64, 1.07]; p = .16), suggesting a protective effect for lower perceived neighborhood crime. Discussion: Lower perceived neighborhood crime is associated with reduced presence of elevated symptoms of depression in older Latinos. C1 [Hernandez, Rosalba] Univ Illinois, Urbana, IL 61801 USA. [Kershaw, Kiarri N.] Northwestern Univ, Chicago, IL 60611 USA. [Prohaska, Thomas R.] George Mason Univ, Fairfax, VA 22030 USA. [Wang, Pin-Chieh; Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Marquez, David X.] Univ Illinois, Chicago, IL USA. [Sarkisian, Catherine A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hernandez, R (reprint author), Univ Illinois, Sch Social Work, 1010 W Nevada St, Urbana, IL 61801 USA. EM rherna17@illinois.edu FU National Institute on Aging of the National Institutes of Health [R01 AG024460-05, P30AG028748, K24AG047899]; 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] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R01 AG024460-05, P30AG028748 (UCLA Claude D. Pepper Older Americans Independence Center), and K24AG047899. 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. Rosalba Hernandez was a T32 Post-Doctoral Fellow on NHLBI T32 HL 069771-10 (Daviglus, PI) when initially drafting this manuscript. NR 39 TC 4 Z9 4 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 EI 1552-6887 J9 J AGING HEALTH JI J. Aging Health PD APR PY 2015 VL 27 IS 3 BP 551 EP 568 DI 10.1177/0898264314553211 PG 18 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA CI2BO UT WOS:000354549800008 PM 25326129 ER PT J AU Race, E Palombo, DJ Cadden, M Burke, K Verfaellie, M AF Race, Elizabeth Palombo, Daniela J. Cadden, Margaret Burke, Keely Verfaellie, Mieke TI Memory integration in amnesia: Prior knowledge supports verbal short-term memory SO NEUROPSYCHOLOGIA LA English DT Article DE Amnesia; Hippocampus; Medial temporal lobe; Schema; Long-term memory ID MEDIAL TEMPORAL-LOBE; SELECTIVE HIPPOCAMPAL-LESIONS; VISUAL WORKING-MEMORY; EPISODIC BUFFER; LOCATION ASSOCIATIONS; RELATIONAL BINDING; IMPLICIT BINDING; RECOGNITION; LONG; INFORMATION AB Short-term memory (STM) and long-term memory (LTM) have traditionally been considered cognitively distinct. However, it is known that STM can improve when to-be-remembered information appears in contexts that make contact with prior knowledge, suggesting a more interactive relationship between STM and LTM. The current study investigated whether the ability to leverage LTM in support of STM critically depends on the integrity of the hippocampus. Specifically, we investigated whether the hippocampus differentially supports between-domain versus within-domain STM-LTM integration given prior evidence that the representational domain of the elements being integrated in memory is a critical determinant of whether memory performance depends on the hippocampus. In Experiment 1, we investigated hippocampal contributions to within-domain STM-LTM integration by testing whether immediate verbal recall of words improves in MTL amnesic patients when words are presented in familiar verbal contexts (meaningful sentences) compared to unfamiliar verbal contexts (random word lists). Patients demonstrated a robust sentence superiority effect, whereby verbal STM performance improved in familiar compared to unfamiliar verbal contexts, and the magnitude of this effect did not differ from that in controls. In Experiment 2, we investigated hippocampal contributions to between-domain STM-LTM integration by testing whether immediate verbal recall of digits improves in MTL amnesic patients when digits are presented in a familiar visuospatial context (a typical keypad layout) compared to an unfamiliar visuospatial context (a random keypad layout). Immediate verbal recall improved in both patients and controls when digits were presented in the familiar compared to the unfamiliar keypad array, indicating a preserved ability to integrate activated verbal information with stored visuospatial knowledge. Together, these results demonstrate that immediate verbal recall in amnesia can benefit from two distinct types of semantic support, verbal and visuospatial, and that the hippocampus is not critical for leveraging stored semantic knowledge to improve memory performance. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Race, Elizabeth] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. RP Race, E (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 150S Huntington Ave 151-A, Boston, MA 02130 USA. EM race@bu.edu FU NIH [F32NS073212]; Department of Veterans Affairs Clinical Science Research and Development Service FX This research was supported by NIH grant F32NS073212 and by the Department of Veterans Affairs Clinical Science Research and Development Service. NR 60 TC 2 Z9 2 U1 11 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD APR PY 2015 VL 70 BP 272 EP 280 DI 10.1016/j.neuropsychologia.2015.02.004 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CI2SI UT WOS:000354596900028 PM 25752585 ER PT J AU Olson, KR Caldwell, A Sihombing, M Guarino, AJ Nelson, BD Petersen, R AF Olson, Kristian R. Caldwell, Aya Sihombing, Melva Guarino, A. J. Nelson, Brett D. Petersen, Rebecca TI Assessing self-efficacy of frontline providers to perform newborn resuscitation in a low-resource setting SO RESUSCITATION LA English DT Article DE Self-efficacy; Newborn resuscitation; Developing country; Newborn health; Neonatal mortality; Birth asphyxia ID NEONATAL RESUSCITATION; BABIES; SCALE; STILLBIRTHS; MORTALITY; DEATHS AB Objectives: Newborn deaths comprise an alarming proportion of under-five mortality globally. In this retrospective cohort study, we investigated the effectiveness of focused newborn resuscitation training and delivery of a positive-pressure device in a rural midwife population in a low-resource setting. The present research attempts to better understand the extent to which knowledge and self-efficacy contribute to resuscitation attempts by birth attendants in practice. Methods: A one-year retrospective cohort analysis was undertaken in Aceh, Indonesia of two groups of community-based midwives, one having received formal training and a positive-pressure resuscitative device and the other receiving usual educational resources and management. A path analysis was undertaken to evaluate relative determinants of actual resuscitation attempts. Results: 348 community-based midwives participated in the evaluation and had attended 3116 births during the preceding year. Path analysis indicated that formal training in resuscitation and delivery of a positive-pressure device were significantly related to both increased knowledge (beta = 0.55, p = 0.001) and increased self-efficacy (beta = 0.52, p = 0.001) in performing neonatal resuscitations with a positive-pressure device. However, training impacted actual resuscitation attempts only indirectly through a relationship with self-efficacy and with knowledge. Combined across groups, self-efficacy was significantly associated with positive pressure ventilation attempts (beta = 0.26, p < 0.01) whereas knowledge was not (beta = -0.05, p = 0.39). Conclusion: Although, to date, evaluations of newborn resuscitation programs have primarily focused on training and has reported process indicators, these results indicate that in order to improve intrapartum-related hypoxic events ("birth asphyxia"), increased emphasis should be placed on participant self-efficacy and mastery of newborn resuscitation. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Olson, Kristian R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Olson, Kristian R.] Massachusetts Gen Hosp, Dept Med, Clinician Educ Unit, Boston, MA 02114 USA. [Olson, Kristian R.; Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Olson, Kristian R.; Nelson, Brett D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Caldwell, Aya] Novartis Fdn Sustainable Dev, CH-4002 Basel, Switzerland. [Sihombing, Melva] Bina Permata Med Sch Hlth Sci, Tangerang, Banten, Indonesia. [Guarino, A. J.; Petersen, Rebecca] MGH Inst Hlth Profess, Charlestown, MA 02129 USA. RP Olson, KR (reprint author), Massachusetts Gen Hosp, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM krolson@partners.org OI Nelson, Brett/0000-0002-5049-1798 NR 26 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD APR PY 2015 VL 89 BP 58 EP 63 DI 10.1016/j.resuscitation.2015.01.008 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA CI1ZM UT WOS:000354543900015 PM 25613363 ER PT J AU Nair, AV Keliher, EJ Core, AB Brown, D Weissleder, R AF Nair, Anil V. Keliher, Edmund J. Core, Amanda B. Brown, Dennis Weissleder, Ralph TI Characterizing the Interactions of Organic Nanoparticles with Renal Epithelial Cells in Vivo SO ACS NANO LA English DT Article DE nanotechnology; dextran; nanoparticles; kidney; epithelial cells; toxicity ID QUANTUM DOTS; PROXIMAL TUBULE; KIDNEY; TOXICITY; ALBUMIN; RETRIEVAL; DEXTRAN; DENDRIMERS; CLEARANCE; MEGALIN AB Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed On the effects of these materials on targeted tumor or phagocytic cells, relatively little is known about their effects on renal cells. This becomes critical for supersmall nanoparticles (<10 nm), designed to be renally excreted. The active endocytic machinery of kidney proximal tubules avidly internalizes filtered proteins, which may also be the case for filtered nanoparticles. To test whether such interactions affect kidney function, we injected mice with either 5 nm dextran-based nanoparticles (DNP) that are similar in composition to FDA-approved materials or poly(amido amine) dendrimer nanoparticles (PNP) of comparable size. These fluorescently tagged nanoparticles were both filtered and internalized by renal tubular epithelial cells in a dose- and time-dependent fashion. The biological effects were quantitated by immunocytochemistry, measuring kidney injury markers and performing functional tests. DNP administration resulted in a dose-dependent increase in urinary output, while cellular albumin endocytosis was increased. The expression of megalin, a receptor involved in albumin uptake, was also increased, but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression and increased endocytosis of dextran. We conclude that there are no major detrimental renal effects of DNP on overall kidney function, but changes in endocytosis-mediating protein expression do occur. These studies provide a framework for the testing of additional nanoparticle preparations as they become available. C1 [Nair, Anil V.; Keliher, Edmund J.; Core, Amanda B.; Brown, Dennis; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nair, Anil V.; Core, Amanda B.; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Nair, Anil V.; Core, Amanda B.; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NHLBI NIH HHS [HHSN268201000044C]; NIDDK NIH HHS [DK96586, DK43351, DK57521, P30 DK043351, P30 DK057521, R01 DK096586]; PHS HHS [HHSN268201000044C] NR 33 TC 6 Z9 6 U1 4 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD APR PY 2015 VL 9 IS 4 BP 3641 EP 3653 DI 10.1021/acsnano.5b00428 PG 13 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CH2PL UT WOS:000353867000026 PM 25790730 ER PT J AU Imler, TD Morea, J Kahi, C Cardwell, J Johnson, CS Xu, HP Ahnen, D Antaki, F Ashley, C Baffy, G Cho, I Dominitz, J Hou, J Korsten, M Nagar, A Promrat, K Robertson, D Saini, S Shergill, A Smalley, W Imperiale, TF AF Imler, Timothy D. Morea, Justin Kahi, Charles Cardwell, Jon Johnson, Cynthia S. Xu, Huiping Ahnen, Dennis Antaki, Fadi Ashley, Christopher Baffy, Gyorgy Cho, Ilseung Dominitz, Jason Hou, Jason Korsten, Mark Nagar, Anil Promrat, Kittichai Robertson, Douglas Saini, Sameer Shergill, Amandeep Smalley, Walter Imperiale, Thomas F. TI Multi-Center Colonoscopy Quality Measurement Utilizing Natural Language Processing SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ADENOMA DETECTION RATE; ELECTRONIC MEDICAL-RECORDS; COLORECTAL-CANCER; SURVEILLANCE COLONOSCOPY; AUTOMATED IDENTIFICATION; DETECTION RATES; RECOMMENDATIONS; POLYPECTOMY; PERFORMANCE; RISK AB BACKGROUND: An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP). METHODS: From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures. RESULTS: A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0-99.8%). Accuracy for number of adenomas was 92%. CONCLUSIONS: NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings. C1 [Imler, Timothy D.; Kahi, Charles; Imperiale, Thomas F.] Indiana Univ, Div Gastroenterol & Hepatol, Indianapolis, IN 46204 USA. [Imler, Timothy D.; Morea, Justin; Kahi, Charles; Imperiale, Thomas F.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA. [Imler, Timothy D.; Morea, Justin] Regenstrief Inst LLC, Dept Biomed Informat, Indianapolis, IN USA. [Kahi, Charles; Cardwell, Jon; Imperiale, Thomas F.] Richard L Roudebush VA Med Ctr, Ctr Innovat Hlth Serv Res & Dev, Indianapolis, IN USA. [Johnson, Cynthia S.; Xu, Huiping] Indiana Univ, Sch Med, Dept Biostat, Indianapolis, IN 46204 USA. [Ahnen, Dennis] Univ Colorado, Div Gastroenterol, Denver, CO 80202 USA. [Antaki, Fadi] Wayne State Univ, Div Gastroenterol, Detroit, MI USA. [Ashley, Christopher] Albany Med Coll, Div Gastroenterol, Albany, NY 12208 USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Cho, Ilseung] NYU, Sch Med, Div Gastroenterol, New York, NY USA. [Dominitz, Jason] Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA 98195 USA. [Hou, Jason] Baylor Coll Med, Div Gastroenterol & Hepatol, Houston, TX 77030 USA. [Korsten, Mark] Icahn Sch Med Mt Sinai, Div Gastroenterol, Bronx, NY USA. [Nagar, Anil] Yale Univ, Sch Med, Div Digest Dis, New Haven, CT USA. [Promrat, Kittichai] Brown Med Sch, Div Gastroenterol, Providence, RI USA. [Robertson, Douglas] Dartmouth Inst, Div Gastroenterol, Lebanon, NH USA. [Saini, Sameer] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Shergill, Amandeep] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Smalley, Walter] Vanderbilt Univ, Div Gastroenterol, Nashville, TN 37235 USA. [Imperiale, Thomas F.] Regenstrief Inst Hlth Care, Hlth Serv Res, Indianapolis, IN USA. RP Imler, TD (reprint author), Regenstrief Inst Hlth Care, Div Gastroenterol & Hepatol, 702 Rotary Circle,Suite 225, Indianapolis, IN 46202 USA. EM timler@iu.edu OI Cho, Ilseung/0000-0002-7308-8707; Dominitz, Jason/0000-0002-8070-7086 FU Veterans Administration Merit Review Grant [IIR 08-062]; American Society for Gastrointestinal Endoscopy Covidien Senior Investigator Mentoring Award; Mamlin-McDonald Biomedical Informatics Fellowship; American Society for Gastrointestinal Endoscopy Career Development Award; Regenstrief Institute Innovations Award FX We acknowledge the Roudebush VAMC (Center of Excellence on Implementing Evidence-Based Practice, Health Services Research & Development (HSR&D)), Eric Sherer, Ph.D., Mae Go, Nina Kinnard, Brian Brake, Lynn Cottee, Tenesha Franks, Belinda Dalton, Jeff Fahner, Stephan Eisenbarth, Gina Donofrio, Annette Sobczyk, Elizabeth Kratts, Ricahrd Ray, Matt Rafus, Jim Vecchi, Maria Schay, Glenn Zwinger, Richard Crockett, Kathy Taylor, Sean Nelson, Patrick Ferguson, Miachel Raffanello, Robert Ziskin, Peter Lee, Joan Hidalgo, Joseph George, Jon Cardwell, and Jason Larson for the data extraction and manipulation assistance. We are extremely grateful to our additional annotators, Drs Nabil Fayad and Howard Matsuoka for their time and effort in creating the gold standard. We thank the Albany, Ann Arbor, Bronx, Denver, Detroit, Houston, Indianapolis, Nashville, New York Harbor, Northport, San Francisco, West Haven, and White River Junction VAs for their contribution of the data. Dr Timothy Imler had full access to all of the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. The authors disclose that Drs Imler and Morea have filed for provisional patent (IURTC-14098-01-US-E) for this work under the name Tracking Real-time Assessment of Quality Monitoring in Endoscopy (TRAQ-ME) through the Indiana University Research and Technology Corporation (IURTC). This work was performed at the Regenstrief Institute, Indianapolis, Indiana, and was supported in part by the Veterans Administration Merit Review Grant IIR 08-062 (Imperiale), the American Society for Gastrointestinal Endoscopy Covidien Senior Investigator Mentoring Award (Imperiale), the Mamlin-McDonald Biomedical Informatics Fellowship (Morea), the American Society for Gastrointestinal Endoscopy Career Development Award (Imler), and the Regenstrief Institute Innovations Award (Imler). Written permission obtained from all persons named here. NR 37 TC 9 Z9 9 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2015 VL 110 IS 4 BP 543 EP 552 DI 10.1038/ajg.2015.51 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CH4ZA UT WOS:000354042000012 PM 25756240 ER PT J AU Leow, JJ Orsola, A Chang, SL Bellmunt, J AF Leow, Jeffrey J. Orsola, Anna Chang, Steven L. Bellmunt, Joaquim TI A contemporary review of management and prognostic factors of upper tract urothelial carcinoma SO CANCER TREATMENT REVIEWS LA English DT Review DE Upper tract; Urothelial; Ureteral neoplasms; Kidney neoplasms; Nephroureterectomy; Surgery; Prognosis; Intravesical therapy; Radiotherapy; Chemotherapy ID UPPER-URINARY-TRACT; TRANSITIONAL-CELL-CARCINOMA; EMISSION TOMOGRAPHY/COMPUTERIZED TOMOGRAPHY; LAPAROSCOPIC RADICAL NEPHROURETERECTOMY; ADJUVANT SYSTEMIC CHEMOTHERAPY; RANDOMIZED CLINICAL-TRIAL; DISEASE-SPECIFIC SURVIVAL; UROPLAKIN-III EXPRESSION; BACILLUS-CALMETTE-GUERIN; CANCER-SPECIFIC SURVIVAL AB Background: Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. Methods: A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Results: Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits.. Minimally invasive surgery has equivalent oncologic and better pen-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Conclusion: Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Leow, Jeffrey J.; Orsola, Anna; Chang, Steven L.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leow, Jeffrey J.; Chang, Steven L.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Leow, Jeffrey J.; Chang, Steven L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Bellmunt, Joaquim] IMIM Hosp Mar, Barcelona, Spain. RP Bellmunt, J (reprint author), Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM joaquim_bellmunt@dfci.harvard.edu NR 175 TC 6 Z9 8 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD APR PY 2015 VL 41 IS 4 BP 310 EP 319 DI 10.1016/j.ctrv.2015.02.006 PG 10 WC Oncology SC Oncology GA CH2LI UT WOS:000353856300002 PM 25736461 ER PT J AU Valenca, LB Sweeney, CJ Pomerantz, MM AF Valenca, Loana B. Sweeney, Christopher J. Pomerantz, Mark M. TI Sequencing current therapies in the treatment of metastatic prostate cancer SO CANCER TREATMENT REVIEWS LA English DT Review DE Prostate cancer; mCRPC; Sequencing; Combination; Cross-resistance ID MAXIMUM ANDROGEN-BLOCKADE; RANDOMIZED CONTROLLED-TRIALS; ABIRATERONE ACETATE; ENZALUTAMIDE MDV3100; ANTITUMOR-ACTIVITY; CLINICAL ACTIVITY; INCREASED SURVIVAL; CROSS-RESISTANCE; HORMONAL-THERAPY; SIPULEUCEL-T AB The standard treatment for metastatic prostate cancer is androgen deprivation therapy. However, progressive, metastatic disease usually develops, giving rise to metastatic castration-resistant prostate cancer (mCRPC). Great improvements have been made recently in the management of mCRPC, with current approved treatments including chemotherapy, androgen receptor-targeted agents, immunotherapies and radiopharmaceuticals. While the emergence of multiple effective therapies is encouraging, devising a treatment strategy can be difficult and it is becoming increasingly important, and challenging, to identify factors that influence the ideal timing of specific therapies. Considering where to place these agents in the treatment schedule of mCRPC, or whether these agents should be sequenced or combined to derive the optimal benefit for the patient, is not yet clear. Furthermore, cross-resistance may exist between these agents, which may ultimately influence treatment decisions and sequence choices. Preliminary data are emerging regarding the safety and activity for sequential treatment regimens, but there are currently no prospective studies. As prostate cancer is highly heterogeneous clinically, it is likely that no single treatment sequence will be optimal for all patients. However, at present, there are no validated biomarkers to guide individualized treatment for mCRPC. Here we review available data for the different mCRPC treatments, discussing potential sequencing of agents and possible cross-resistance or synergy among the recently approved and emerging therapies. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Valenca, Loana B.; Sweeney, Christopher J.; Pomerantz, Mark M.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Pomerantz, MM (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02215 USA. EM Mark_Pomerantz@dfci.harvard.edu FU Sanofi - United States FX Formatting and proofing services were provided by MediTech Media, funded by Sanofi - United States. NR 105 TC 15 Z9 15 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD APR PY 2015 VL 41 IS 4 BP 332 EP 340 DI 10.1016/j.ctrv.2015.02.010 PG 9 WC Oncology SC Oncology GA CH2LI UT WOS:000353856300004 PM 25784591 ER PT J AU Daselaar, SM Iyengar, V Davis, SW Eklund, K Hayes, SM Cabeza, RE AF Daselaar, Sander M. Iyengar, Vijeth Davis, Simon W. Eklund, Karl Hayes, Scott M. Cabeza, Roberto E. TI Less Wiring, More Firing: Low-Performing Older Adults Compensate for Impaired White Matter with Greater Neural Activity SO CEREBRAL CORTEX LA English DT Article DE DTI; elderly; fMRI; frontal; MTL; PFC ID MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL-LOBE; RECOGNITION MEMORY; AGE-DIFFERENCES; EXECUTIVE FUNCTION; PREFRONTAL CORTEX; WORKING-MEMORY; BRAIN ACTIVITY; LIFE-SPAN; HIPPOCAMPAL AB The reliable neuroimaging finding that older adults often show greater activity (over-recruitment) than younger adults is typically attributed to compensation. Yet, the neural mechanisms of over-recruitment in older adults (OAs) are largely unknown. Rodent electrophysiology studies have shown that as number of afferent fibers within a circuit decreases with age, the fibers that remain show higher synaptic field potentials (less wiring, more firing). Extrapolating to system-level measures in humans, we proposed and tested the hypothesis that greater activity in OAs compensates for impaired white-matter connectivity. Using a neuropsychological test battery, we measured individual differences in executive functions associated with the prefrontal cortex (PFC) and memory functions associated with the medial temporal lobes (MTLs). Using event-related functional magnetic resonance imaging, we compared activity for successful versus unsuccessful trials during a source memory task. Finally, we measured white-matter integrity using diffusion tensor imaging. The study yielded 3 main findings. First, low-executive OAs showed greater success-related activity in the PFC, whereas low-memory OAs showed greater success-related activity in the MTLs. Second, low-executive OAs displayed white-matter deficits in the PFC, whereas low-memory OAs displayed white-matter deficits in the MTLs. Finally, in both prefrontal and MTL regions, white-matter decline and success-related activations occurred in close proximity and were negatively correlated. This finding supports the lesswiring- more-firing hypothesis, which provides a testable account of compensatory over-recruitment in OAs. C1 [Daselaar, Sander M.; Iyengar, Vijeth; Eklund, Karl; Cabeza, Roberto E.] Duke Univ, Ctr Cognit Neurosci, Durham, NC 27708 USA. [Daselaar, Sander M.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 HR Nijmegen, Netherlands. [Davis, Simon W.] Univ Cambridge, Dept Psychol, Ctr Speech Language & Brain, Cambridge CB2 3EB, England. [Hayes, Scott M.] Boston Univ, VA Boston Healthcare Syst, Memory Disorders Res Ctr, Sch Med, Boston, MA 02130 USA. [Hayes, Scott M.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. RP Daselaar, SM (reprint author), Duke Univ, Ctr Cognit Neurosci, Durham, NC 27708 USA. EM s.daselaars@donder.ru.nl OI Davis, Simon/0000-0002-5943-0756 FU National Institutes of Health (NIH) [R01 AG019731, R01 AG23770, F32 AG029738]; Department of Veterans Affairs (VA), Rehabilitation Research & Development Service [E7822W]; National Science Foundation (NSF) Graduate Research Fellowship [110640] FX This work was supported by the National Institutes of Health (NIH) (grant numbers R01 AG019731 and R01 AG23770 awarded to R.C. and grant number F32 AG029738 awarded to S.M.H.), the Department of Veterans Affairs (VA), Rehabilitation Research & Development Service (grant number E7822W awarded to S.M.H.), and the National Science Foundation (NSF) Graduate Research Fellowship (grant number 110640 awarded to V.I.). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH, VA, or NSF. NR 47 TC 17 Z9 17 U1 5 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2015 VL 25 IS 4 BP 983 EP 990 DI 10.1093/cercor/bht289 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CH2EN UT WOS:000353838600014 PM 24152545 ER PT J AU Jowett, N Hadlock, TA AF Jowett, Nate Hadlock, Tessa A. TI Contemporary Management of Bell Palsy SO FACIAL PLASTIC SURGERY LA English DT Article DE Bell palsy; facial reanimation; synkinesis; facial paralysis; facial palsy ID IDIOPATHIC FACIAL PARALYSIS; QUALITY-OF-LIFE; GRACILIS MUSCLE TRANSFER; RAMSAY-HUNT-SYNDROME; PROGNOSTIC-FACTORS; LYME-DISEASE; NERVE PALSY; RECONSTRUCTION; REANIMATION; SYNKINESIS AB Bell palsy (BP) is the most common diagnosis in acute and chronic facial palsy. Although most patients fully recover, more than one-quarter will have residual dysfunction. Of these, nearly half will demonstrate severe limitations in facial expression. Though significant attention has been paid to acute management and prognosis, a paucity of literature exists addressing management of the long-term sequelae of BP. This article describes contemporary use of physical therapy, injectables, and static and dynamic surgical procedures in facial reanimation of acute and chronic BP. C1 [Jowett, Nate; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Jowett, Nate; Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. RP Jowett, N (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM nathan_jowett@meei.harvard.edu NR 52 TC 3 Z9 3 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 EI 1098-8793 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD APR PY 2015 VL 31 IS 2 BP 93 EP 102 DI 10.1055/s-0035-1549040 PG 10 WC Surgery SC Surgery GA CH8HI UT WOS:000354276600002 PM 25958893 ER PT J AU Lupon, J Gaggin, HK de Antonio, M Domingo, M Galan, A Zamora, E Vila, J Penafiel, J Urrutia, A Ferrer, E Vallejo, N Januzzi, JL Bayes-Genis, A AF Lupon, Josep Gaggin, Hanna K. de Antonio, Marta Domingo, Mar Galan, Amparo Zamora, Elisabet Vila, Joan Penafiel, Judith Urrutia, Agustin Ferrer, Elena Vallejo, Nuria Januzzi, James L. Bayes-Genis, Antoni TI Biomarker-assist score for reverse remodeling prediction in heart failure: The ST2-R2 score SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Heart failure; Reverse remodeling; LVEF; Biomarkers; ST2 ID CARDIAC RESYNCHRONIZATION THERAPY; VENTRICULAR SYSTOLIC DYSFUNCTION; NATRIURETIC PEPTIDE; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; ECHOCARDIOGRAPHY; IMPROVEMENT; ASSOCIATION; CARVEDILOL AB Background: Limited data exists regarding biomarker use to predict left ventricular (LV) reverse remodeling (R2). Our aim was to examine the value of soluble ST2 (ST2), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and galectin-3 relative to LV-R2 in systolic heart failure (HF), and to develop a clinical score for LV-R2 prediction. Methods: R2 was defined as a) LV ejection fraction (LVEF) increase >= 15%, or b) LVEF increase >= 10% plus reduction of LV end-systolic diameter index >= 20% or LV end-systolic volume >= 40%, for 12 months. Results: We studied 304 patients (79.6% men, mean age 66.1 +/- 12.3 years) with baseline LVEF <40%. R2 was observed in 104 patients (34.2%). In univariable logistic regression, factors associatedwith R2 were age (p = 0.02), non-ischemic etiology of HF (p < 0.001), NYHA functional class (p = 0.02), baseline LVEF (p = 0.005), absence of left bundle branch block (LBBB; p = 0.002), ST2 (p = 0.004), NT-proBNP (p = 0.005), and hs-cTnT (p < 0.001); HF duration achieved borderline significance (p = 0.08). In multivariable analysis, ST2 remained the only biomarker associated with LV-R2. We developed the ST2-R2 score for use in clinical practice for predicting R2; variables included were ST2 <48 ng/mL, non-ischemic etiology, absence of LBBB, HF duration <12 months, baseline LVEF <24%, and beta-blocker treatment. The score had an area under the curve of 0.79 in the derivation cohort and 0.73 in a separate validation cohort. Conclusions: The ST2-R2 score, which includes the novel biomarker ST2 and five clinical variables, reasonably predicts LV-R2 in systolic HF patients. ST2 was the only studied biomarker that was independently associated with R2. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Lupon, Josep; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Urrutia, Agustin; Ferrer, Elena; Vallejo, Nuria; Bayes-Genis, Antoni] Hosp Badalona Germans Trias & Pujol, Serv Cardiol, Badalona, Spain. [Lupon, Josep; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Urrutia, Agustin; Ferrer, Elena; Vallejo, Nuria; Bayes-Genis, Antoni] Hosp Badalona Germans Trias & Pujol, Heart Failure Unit, Badalona, Spain. [Lupon, Josep; de Antonio, Marta; Zamora, Elisabet; Urrutia, Agustin; Bayes-Genis, Antoni] Autonomous Univ Barcelona, Dept Med, Barcelona, Spain. [Gaggin, Hanna K.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Galan, Amparo] Hosp Badalona Germans Trias & Pujol, Serv Biochem, Badalona, Spain. [Vila, Joan; Penafiel, Judith] Hosp del Mar, Med Res Inst, IMIM, Barcelona, Spain. [Vila, Joan; Penafiel, Judith] CIBER, Epidemiol & Publ Hlth, Barcelona, Spain. RP Bayes-Genis, A (reprint author), Hosp Badalona Germans Trias & Pujol, Serv Cardiol, Carretera Canyet S-N, Barcelona 08916, Spain. EM abayesgenis@gmail.com OI Lupon, Josep/0000-0002-5601-9611 NR 39 TC 7 Z9 8 U1 2 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 1 PY 2015 VL 184 BP 337 EP 343 DI 10.1016/j.ijcard.2015.02.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH1EL UT WOS:000353763800070 PM 25734941 ER PT J AU Motiwala, SR Gaggin, HK Gandhi, PU Belcher, A Weiner, RB Baggish, AL Szymonifka, J Januzzi, JL AF Motiwala, Shweta R. Gaggin, Hanna K. Gandhi, Parul U. Belcher, Arianna Weiner, Rory B. Baggish, Aaron L. Szymonifka, Jackie Januzzi, James L., Jr. TI Concentrations of Highly Sensitive Cardiac Troponin-I Predict Poor Cardiovascular Outcomes and Adverse Remodeling in Chronic Heart Failure SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Heart failure; Biomarker; Troponin; Prognosis; Remodeling ID 3RD UNIVERSAL DEFINITION; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; THERAPY PROTECT; ASSOCIATION; DYSFUNCTION AB Highly sensitive troponin (hsTn) assays may predict cardiovascular (CV) events and left ventricular (LV) remodeling in patients with heart failure (HF). In this study, 99 subjects with LV systolic dysfunction (LVSD) were followed 10 +/- 3 months with serial measurement of hsTnI by a novel method. hsTnI was detectable in all subjects and was above the 99th percentile of a normal population in 56.7 %. Supramedian baseline hsTnI concentration was associated with higher-risk clinical features and shorter time-to-first event (p = 0.008). Across serial measurements, more time spent a parts per thousand currency sign10.9 pg/mL was associated with a lower CV event rate after adjustment (odds ratio (OR) = 0.81; p = 0.008); rising hsTnI also predicted progressive LV remodeling. In conclusion, hsTnI detected significant myocardial necrosis in a majority of patients with chronic HF due to LVSD and when measured serially, provided independent risk information for poor CV outcomes and deleterious LV remodeling. C1 [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Gaggin, Hanna K.; Gandhi, Parul U.; Belcher, Arianna; Weiner, Rory B.; Baggish, Aaron L.; Szymonifka, Jackie] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Singulex; Dennis and Marilyn Barry Fellowship in Cardiology; Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment FX This work was supported in part by Singulex, which had no role in data analysis or initial manuscript preparation. Dr. Motiwala was supported by the Dennis and Marilyn Barry Fellowship in Cardiology, Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation, and Dr. Januzzi is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment. NR 14 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 EI 1937-5395 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD APR PY 2015 VL 8 IS 3 BP 164 EP 172 DI 10.1007/s12265-015-9618-4 PG 9 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA CH8VQ UT WOS:000354314600003 PM 25777344 ER PT J AU Nodzo, SR Bauer, T Pottinger, PS Garrigues, GE Bedair, H Deirmengian, CA Segreti, J Blount, KJ Omar, IM Parvizi, J AF Nodzo, Scott R. Bauer, Thomas Pottinger, Paul S. Garrigues, Grant E. Bedair, Hany Deirmengian, Carl A. Segreti, John Blount, Kevin J. Omar, Imran M. Parvizi, Javad TI Conventional Diagnostic Challenges in Periprosthetic Joint Infection SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID REVISION SHOULDER ARTHROPLASTY; POSITIVE INTRAOPERATIVE CULTURES; TOTAL KNEE ARTHROPLASTY; DUAL-ENERGY CT; PROPIONIBACTERIUM-ACNES; SYNOVIAL-FLUID; MUSCULOSKELETAL INFECTION; ALPHA-DEFENSIN; DIABETIC FOOT; OSTEOMYELITIS AB Periprosthetic joint infection remains a clinical challenge with no benchmark for diagnosis. The diagnosis is based on many different clinical variables that may be difficult to interpret, especially in the setting of chronic systemic disease. Synovial fluid aspiration, diagnostic imaging, traditional culture, peripheral serum inflammatory markers, and intraoperative frozen sections each have their limitations but continue to be the mainstay for diagnosis of periprosthetic joint infection. As molecular- and biomarker-based technologies improve, the way we interpret and diagnose periprosthetic joint infection will ultimately change and may even improve diagnostic accuracy and turnaround time. Future research on this topic should be focused on improving diagnostic criteria for low-virulence organisms, improving interpretation of intraoperative frozen sections, and establishing improved synovial fluid and peripheral serum biomarker profiles for periprosthetic joint infection. C1 [Nodzo, Scott R.] SUNY Buffalo, Dept Orthopaed, Buffalo, NY 14214 USA. [Bauer, Thomas] Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. [Pottinger, Paul S.] Univ Washington, Seattle, WA 98195 USA. [Garrigues, Grant E.] Duke Univ, Med Ctr, Dept Orthopaed Surg, Durham, NC USA. [Bedair, Hany] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Deirmengian, Carl A.] Rothman Inst, Dept Orthopaed Surg, Philadelphia, PA USA. [Segreti, John] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Blount, Kevin J.; Omar, Imran M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Parvizi, Javad] Thomas Jefferson Univ, Rothman Inst, Philadelphia, PA 19107 USA. RP Nodzo, SR (reprint author), SUNY Buffalo, Dept Orthopaed, Buffalo, NY 14214 USA. NR 64 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD APR PY 2015 VL 23 SU 1 BP S18 EP S25 DI 10.5435/JAAOS-D-14-00385 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CH6ES UT WOS:000354129700004 PM 25808966 ER PT J AU Dobre, M Yang, W Pan, Q Appel, L Bellovich, K Chen, J Feldman, H Fischer, MJ Ham, LL Hostetter, T Jaar, BG Kallem, RR Rosas, SE Scialla, JJ Wolf, M Rahman, M AF Dobre, Mirela Yang, Wei Pan, Qiang Appel, Lawrence Bellovich, Keith Chen, Jing Feldman, Harold Fischer, Michael J. Ham, L. L. Hostetter, Thomas Jaar, Bernard G. Kallem, Radhakrishna R. Rosas, Sylvia E. Scialla, Julia J. Wolf, Myles Rahman, Mahboob CA CRIC Study Investigators TI Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients With Chronic Kidney Disease (CKD): A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE CKD; heart failure; serum bicarbonate ID GLOMERULAR-FILTRATION-RATE; MARGINAL STRUCTURAL MODELS; BASE-LINE CHARACTERISTICS; HIGH BLOOD-PRESSURE; METABOLIC-ACIDOSIS; HYPERTENSIVE NEPHROPATHY; VASCULAR CALCIFICATION; SODIUM-BICARBONATE; MORTALITY; ASSOCIATION AB Background-Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end-stage renal disease), and mortality. Methods and Results-Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time-dependent confounding. During the 6 years follow-up, 512 participants developed congestive heart failure (26/1000 person-years) and 749 developed renal events (37/1000 person-years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow-up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co-morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2-fold increased risk of renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L. Conclusion-In this large CKD cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in CKD to prevent adverse clinical outcomes. C1 [Dobre, Mirela; Hostetter, Thomas; Rahman, Mahboob] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Nephrol & Hypertens, Cleveland, OH 44106 USA. [Rahman, Mahboob] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Yang, Wei; Pan, Qiang; Feldman, Harold] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Appel, Lawrence; Jaar, Bernard G.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Appel, Lawrence; Jaar, Bernard G.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Appel, Lawrence; Jaar, Bernard G.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Bellovich, Keith] St John Hosp & Med Ctr Detroit, Detroit, MI USA. [Chen, Jing; Ham, L. L.] Tulane Univ, Sch Med, Dept Med, Sect Nephrol & Hypertens, New Orleans, LA 70112 USA. [Fischer, Michael J.] Jesse Brown VAMC, Chicago, IL USA. [Fischer, Michael J.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [Kallem, Radhakrishna R.] Univ Penn, Perelman Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Scialla, Julia J.] Duke Univ, Sch Med, Durham, NC USA. [Wolf, Myles] Northwestern Univ, Div Nephrol & Hypertens, Feinberg Sch Med, Chicago, IL 60611 USA. RP Dobre, M (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Nephrol & Hypertens, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Mirela.Dobre@uhhospitals.org FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060 980, U01DK060963, U01DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award [NIH/NCATS UL1TR000003]; Johns Hopkins University [UL1 TR-000424]; University of Maryland [GCRC M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland; National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research [UL1TR000439]; Michigan Institute for Clinical and Health Research (MICHR) [UL1TR000433]; University of Illinois at Chicago [CTSA UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology [P30GM103337]; Kaiser Permanente NIH/NCRR [UCSF-CTSI UL1 RR-024131]; Department of Veterans Affairs Health Services Research and Development Service [13FTF15920005, K23DK095949, R01DK081374] FX Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060 980, U01DK060963, and U01DK060902). In addition, this work was supported in part by: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/NCATS UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131. Dobre was supported by 13FTF15920005. Scialla was supported by K23DK095949. Wolf was supported by R01DK081374. Fischer was supported by Department of Veterans Affairs Health Services Research and Development Service. NR 39 TC 8 Z9 9 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2015 VL 4 IS 4 AR e001599 DI 10.1161/JAHA.114.001599 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6HN UT WOS:000354137300013 ER PT J AU Li, XZ Ballantyne, LL Che, XH Mewburn, JD Kang, JX Barkley, RM Murphy, RC Yu, Y Funk, CD AF Li, Xinzhi Ballantyne, Laurel L. Che, Xinghui Mewburn, Jeffrey D. Kang, Jing X. Barkley, Robert M. Murphy, Robert C. Yu, Ying Funk, Colin D. TI Endogenously Generated Omega-3 Fatty Acids Attenuate Vascular Inflammation and Neointimal Hyperplasia by Interaction With Free Fatty Acid Receptor 4 in Mice SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE adipose tissue; fatty acids; inflammation; omega-3 fatty acid receptor; transgenic model ID PERIVASCULAR ADIPOSE-TISSUE; DOCOSAHEXAENOIC ACID; FISH-OIL; CARDIOVASCULAR-DISEASE; PROINFLAMMATORY PHENOTYPE; EICOSAPENTAENOIC ACID; TRANSGENIC MICE; LIMB ISCHEMIA; MURINE MODEL; MOUSE MODEL AB Background-Omega-3 polyunsaturated fatty acids (omega 3 PUFAs) suppress inflammation through activation of free fatty acid receptor 4 (FFAR4), but this pathway has not been explored in the context of cardiovascular disease. We aimed to elucidate the involvement of FFAR4 activation by omega 3 PUFAs in the process of vascular inflammation and neointimal hyperplasia in mice. Methods and Results-We used mice with disruption of FFAR4 (Ffar4(-/-)), along with a strain that synthesizes high levels of omega 3 PUFAs (fat-1) and a group of crossed mice (Ffar4(-/-)/fat-1), to elucidate the role of FFAR4 in vascular dysfunction using acute and chronic thrombosis/vascular remodeling models. The presence of FFAR4 in vascular-associated cells including perivascular adipocytes and macrophages, but not platelets, was demonstrated. omega 3 PUFAs endogenously generated in fat-1 mice (n=9), but not in compound Ffar4(-/-)/fat-1 mice (n=9), attenuated femoral arterial thrombosis induced by FeCl3. Neointimal hyperplasia and vascular inflammation in the common carotid artery were significantly curtailed 4 weeks after FeCl3 injury in fat-1 mice (n=6). This included greater luminal diameter and enhanced blood flow, reduced intima: media ratio, and diminished macrophage infiltration in the vasculature and perivascular adipose tissue compared with control mice. These effects were attenuated in the Ffar4(-/-)/fat-1 mice. Conclusions-These results indicate that omega 3 PUFAs mitigate vascular inflammation, arterial thrombus formation, and neointimal hyperplasia by interaction with FFAR4 in mice. Moreover, the omega 3 PUFA-FFAR4 pathway decreases inflammatory responses with dampened macrophage transmigration and infiltration. C1 [Li, Xinzhi; Ballantyne, Laurel L.; Che, Xinghui; Funk, Colin D.] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada. [Mewburn, Jeffrey D.] Queens Univ, Canc Res Inst, Kingston, ON K7L 3N6, Canada. [Yu, Ying] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Barkley, Robert M.; Murphy, Robert C.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO USA. RP Funk, CD (reprint author), Queens Univ, Dept Biomed & Mol Sci, Botterell Hall,Room 433,18 Stuart St, Kingston, ON K7L 3N6, Canada. EM funkc@queensu.ca FU Canadian Institutes for Health Research [CCI 117951, NSFC 81161120538]; National Natural Science Foundation of China [CCI 117951, NSFC 81161120538]; Heart and Stroke Foundation of Ontario FX This work was supported by the Joint Health Research Initiative between the Canadian Institutes for Health Research and the National Natural Science Foundation of China (CCI 117951 and NSFC 81161120538). Dr. Funk holds a Tier I Canada Research Chair in Molecular, Cellular and Physiological Medicine and is recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario. NR 65 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2015 VL 4 IS 4 AR e001856 DI 10.1161/JAHA.115.001856 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6HN UT WOS:000354137300029 ER PT J AU Nguyen, PL Jarolim, P Basaria, S Zuflacht, JP Milian, J Kadivar, S Graham, PL Hyatt, A Kantoff, PW Beckman, JA AF Nguyen, Paul L. Jarolim, Petr Basaria, Shehzad Zuflacht, Jonah P. Milian, Jessica Kadivar, Samoneh Graham, Powell L. Hyatt, Andrew Kantoff, Philip W. Beckman, Joshua A. TI Androgen Deprivation Therapy Reversibly Increases Endothelium-Dependent Vasodilation in Men With Prostate Cancer SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE androgen deprivation therapy; endothelial function; inflammation; insulin resistance; prostate cancer ID FLOW-MEDIATED DILATION; LOW-DENSITY-LIPOPROTEIN; POPULATION-BASED COHORT; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; BRACHIAL-ARTERY; MYOCARDIAL-INFARCTION; VASCULAR REACTIVITY; SERUM TESTOSTERONE; METABOLIC SYNDROME AB Background-Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population. Methods and Results-We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 +/- 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05). Conclusions-In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation. C1 [Nguyen, Paul L.; Graham, Powell L.; Hyatt, Andrew] Brigham & Womens Hosp, Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.; Graham, Powell L.; Hyatt, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zuflacht, Jonah P.; Milian, Jessica; Kadivar, Samoneh; Beckman, Joshua A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Basaria, Shehzad] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. RP Beckman, JA (reprint author), 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 FU Watkins Discovery Award; Prostate Cancer Foundation; Fitz's Cancer Warriors; David and Cynthia Chapin FX This study was supported by Watkins Discovery Award, the Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, and a grant from an Anonymous Family Foundation. NR 50 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2015 VL 4 IS 4 AR e001914 DI 10.1161/JAHA.115.001914 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6HN UT WOS:000354137300033 ER PT J AU Jonker, FHW Patel, HJ Upchurch, GR Williams, DM Montgomery, DG Gleason, TG Braverman, AC Sechtem, U Fattori, R Di Eusanio, M Evangelista, A Nienaber, CA Isselbacher, EM Eagle, KA Trimarchi, S AF Jonker, Frederik H. W. Patel, Himanshu J. Upchurch, Gilbert R. Williams, David M. Montgomery, Daniel G. Gleason, Thomas G. Braverman, Alan C. Sechtem, Udo Fattori, Rossella Di Eusanio, Marco Evangelista, Arturo Nienaber, Christoph A. Isselbacher, Eric M. Eagle, Kim A. Trimarchi, Santi TI Acute type B aortic dissection complicated by visceral ischemia SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ACUTE MESENTERIC ISCHEMIA; INTERNATIONAL REGISTRY; ENDOVASCULAR TREATMENT; SURGICAL-MANAGEMENT; INTESTINAL ISCHEMIA; 2ND-LOOK; OUTCOMES; SURGERY AB Objective: Acute type B aortic dissection (ABAD) can lead to visceral malperfusion, a potentially life-threatening complication. The purpose of this study was to investigate the presentation, management, and outcomes of ABAD patients with visceral ischemia who are enrolled in the International Registry of Acute Aortic Dissection. Methods: Patients with ABAD enrolled in the registry between 1996 and 2013 were identified and stratified based on presence of visceral ischemia at admission. Demographics, medical history, imaging results, management, and outcomes were compared for patients with versus without visceral ischemia. Results: A total of 1456 ABAD patients were identified, of which 104 (7.1%) presented with visceral ischemia. Preoperative limb ischemia (28% vs 7%, P < .001) and acute renal failure (41% vs 14%, P < .001) were more common among patients with visceral ischemia. Endovascular treatment and surgery were offered to 49% and 30% of the visceral ischemia cohort, respectively; remaining patients were managed conservatively. The in-hospital mortality was 30.8% for patients with visceral ischemia and 9.1% for those without visceral ischemia (odds ratio [OR] 4.44; 95% confidence interval [CI], 2.8-7.0, P < .0001). Mortality rates were similar after surgical and endovascular management of visceral ischemia (25.8% and 25.5%, respectively, P = not significant). Among the visceral ischemia group, medical management was a predictor of mortality in multivariate analysis (OR, 5.91; 95% CI, 1.2-31.0; P = .036). Conclusions: Patients with ABAD complicated by visceral ischemia have a high risk of mortality. We observed similar outcomes for patients treated by endovascular management versus surgery, whereas medical management was an independent predictor of mortality. Early diagnosis and intervention for visceral ischemia seems to be crucial. C1 [Jonker, Frederik H. W.; Trimarchi, Santi] Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. [Jonker, Frederik H. W.] Erasmus MC, Rotterdam, Netherlands. [Patel, Himanshu J.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Upchurch, Gilbert R.] Univ Virginia, Hlth Syst, Div Vasc & Endovasc Surg, Charlottesville, VA USA. [Williams, David M.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Cardiovasc Ctr, Ann Arbor, MI 48109 USA. [Gleason, Thomas G.] Univ Pittsburgh, Div Cardiothorac Surg, Pittsburgh, PA USA. [Braverman, Alan C.] Washington Univ, Sch Med, Cardiovasc Div, St Louis, MO USA. [Sechtem, Udo] Robert Bosch Krankenhaus, Div Cardiol, Stuttgart, Germany. [Fattori, Rossella] San Salvatore Hosp, Div Intervent Cardiol, Pesaro, Italy. [Di Eusanio, Marco] Univ Hosp S Orsola, Dept Cardiac Surg, Bologna, Italy. [Evangelista, Arturo] Univ Vall Hebron, Gen Hosp, Serv Cardiol, Barcelona, Spain. [Nienaber, Christoph A.] Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. RP Jonker, FHW (reprint author), Policlin San Donato IRCCS, Thorac Aort Res Ctr, Piazza Malan 2, I-20097 San Donato Milanese, Italy. EM jonkerfrederik@hotmail.com RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU Gore Medical Inc. (Flagstaff, Ariz); Ann Bob Aikens; University of Michigan Health System (Ann Arbor, Mich); Varbedian Fund for Aortic Research (Ann Arbor, Mich); Mardigian Foundation (Bloomfield Hills, Mich); Medtronic, Inc. (Minneapolis, Minn) FX This work was supported by grants to the International Registry of Acute Aortic Dissection from Gore Medical Inc. (Flagstaff, Ariz); Ann & Bob Aikens; the University of Michigan Health System (Ann Arbor, Mich); the Varbedian Fund for Aortic Research (Ann Arbor, Mich), the Mardigian Foundation (Bloomfield Hills, Mich), and Medtronic, Inc. (Minneapolis, Minn). NR 29 TC 4 Z9 4 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2015 VL 149 IS 4 BP 1081 EP U519 DI 10.1016/j.jtcvs.2014.11.012 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CG5QG UT WOS:000353347600043 PM 25500101 ER PT J AU Yu, Z Wang, R Fok, WC Coles, A Salmon, AB Perez, VI AF Yu, Zhen Wang, Rong Fok, Wilson C. Coles, Alexander Salmon, Adam B. Perez, Viviana I. TI Rapamycin and Dietary Restriction Induce Metabolically Distinctive Changes in Mouse Liver SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Rapamycin; Dietary restriction; Metabolites; beta-oxidation ID INDUCED INSULIN-RESISTANCE; FATTY-ACID-METABOLISM; CALORIC RESTRICTION; GLUCOSE-METABOLISM; LIFE-SPAN; SKELETAL-MUSCLE; SMOOTH-MUSCLE; MICE; ACTIVATION; SIROLIMUS AB Dietary restriction (DR) is the gold standard intervention used to delay aging, and much recent research has focused on the identification of possible DR mimetics. Energy sensing pathways, including insulin/IGF1 signaling, sirtuins, and mammalian Target of Rapamycin (mTOR), have been proposed as pathways involved in the antiaging actions of DR, and compounds that affect these pathways have been suggested to act as DR mimetics, including metformin (insulin/IGF1 signaling), resveratrol (sirtuins), and rapamycin (mTOR). Rapamycin is a promising DR mimetic because it significantly increases both health span and life span in mice. Unfortunately, rapamycin also leads to some negative effects, foremost among which is the induction of insulin resistance, potentially limiting its translation into humans. To begin clarifying the mechanism(s) involved in insulin resistance induced by rapamycin, we compared several aspects of liver metabolism in mice treated with DR or rapamycin for 6 months. Our data suggest that although both DR and rapamycin inhibit lipogenesis, activate lipolysis, and increased serum levels of nonesterified fatty acids, only DR further activates beta-oxidation of the fatty acids leading to the production of ketone bodies. C1 [Yu, Zhen; Wang, Rong; Perez, Viviana I.] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. [Fok, Wilson C.] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Norman, OK 73019 USA. [Fok, Wilson C.] Oklahoma City VA Med Ctr, Oklahoma City, OK USA. [Coles, Alexander] Univ Michigan Flint, Dept Chem & Biochem, Flint, MI USA. [Salmon, Adam B.] South Texas Vet Hlth Care Syst, Dept Mol Med, San Antonio, TX USA. [Salmon, Adam B.] Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Salmon, Adam B.] Audie Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Perez, Viviana I.] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. RP Perez, VI (reprint author), Oregon State Univ, Linus Pauling Inst, Dept Biochem & Biophys, Linus Pauling Sci Ctr 307, Corvallis, OR 97331 USA. EM viviana.perez@oregonstate.edu OI Fok, Wilson Chun Yim/0000-0003-3289-2093 FU National Institutional of Health (NIH) [AG036613]; San Antonio Nathan Shock Aging Center [1P30-AG-13319]; NIH [AG021890]; Ellison Medical Foundation; Department of Biochemistry and Biophysics; Linus Pauling Institute FX Financial support was provided by National Institutional of Health (NIH) RC2 Grand Opportunity grant (AG036613 to A.R.), The San Antonio Nathan Shock Aging Center (1P30-AG-13319 to A.R.), NIH T32 Training Grant (AG021890 to W.F.), and The Ellison Medical Foundation (V.I.P.), and start-up funds from the Department of Biochemistry and Biophysics and The Linus Pauling Institute (V.I.P.). NR 46 TC 5 Z9 5 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2015 VL 70 IS 4 BP 410 EP 420 DI 10.1093/gerona/glu053 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH2ZW UT WOS:000353896100002 PM 24755936 ER PT J AU Cheng, S Larson, MG McCabe, EL Murabito, JM Rhee, EP Ho, JE Jacques, PF Ghorbani, A Magnusson, M Souza, AL Deik, AA Pierce, KA Bullock, K O'Donnell, CJ Melander, O Clish, CB Vasan, RS Gerszten, RE Wang, TJ AF Cheng, Susan Larson, Martin G. McCabe, Elizabeth L. Murabito, Joanne M. Rhee, Eugene P. Ho, Jennifer E. Jacques, Paul F. Ghorbani, Anahita Magnusson, Martin Souza, Amanda L. Deik, Amy A. Pierce, Kerry A. Bullock, Kevin O'Donnell, Christopher J. Melander, Olle Clish, Clary B. Vasan, Ramachandran S. Gerszten, Robert E. Wang, Thomas J. TI Distinct metabolomic signatures are associated with longevity in humans SO NATURE COMMUNICATIONS LA English DT Article ID MITOCHONDRIAL NADP(+)-ISOCITRATE DEHYDROGENASE; GENOME-WIDE ASSOCIATION; BILE-ACIDS; CARDIOVASCULAR HEALTH; LIFE-SPAN; ISOCITRATE DEHYDROGENASE; HYPERTROPHY DEVELOPMENT; CAENORHABDITIS-ELEGANS; GLUCOSE-HOMEOSTASIS; CARDIAC-HYPERTROPHY AB Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death. C1 [Cheng, Susan; Larson, Martin G.; Murabito, Joanne M.; Ho, Jennifer E.; O'Donnell, Christopher J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Cheng, Susan; Larson, Martin G.; Murabito, Joanne M.; Ho, Jennifer E.; O'Donnell, Christopher J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham, MA 01702 USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02115 USA. [McCabe, Elizabeth L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA 02118 USA. [Rhee, Eugene P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Renal, Boston, MA 02116 USA. [Ho, Jennifer E.; Ghorbani, Anahita; O'Donnell, Christopher J.; Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02116 USA. [Ho, Jennifer E.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02118 USA. [Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Magnusson, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, SE-22100 Lund, Sweden. [Souza, Amanda L.; Deik, Amy A.; Pierce, Kerry A.; Bullock, Kevin; Clish, Clary B.; Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA 02118 USA. [Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02116 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37232 USA. RP Gerszten, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02116 USA. EM rgerszten@partners.org; thomas.j.wang@vanderbilt.edu OI Ho, Jennifer/0000-0002-7987-4768; Magnusson, Martin/0000-0003-1710-5936; Ramachandran, Vasan/0000-0001-7357-5970 FU NIH [N01-HC-25195, R00-HL-107642, R01-DK-HL-081572, R01-HL-098280, U01-HL-107440, R01-AG-29451, K08-DK-090142, K23-HL-116780]; Ellison Foundation; Lerner Award; Leducq Foundation; American Heart Association [12IRG9130006] FX This work was supported by NIH contract N01-HC-25195 and grants R00-HL-107642 (S.C.), R01-DK-HL-081572 (R.E.G. and T.J.W.), R01-HL-098280 (R.E.G.), U01-HL-107440 (R.E.G.), R01-AG-29451 (J.M.M.), K08-DK-090142 (E.P.R.), K23-HL-116780 (J.E.H.), as well as the Ellison Foundation (S.C.), Lerner Award (S.C.), Leducq Foundation (R.E.G.) and American Heart Association grant 12IRG9130006 (R.E.G.). NR 69 TC 10 Z9 10 U1 6 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6791 DI 10.1038/ncomms7791 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IH UT WOS:000353702500031 PM 25864806 ER PT J AU Saladin, ME McClure, EA Baker, NL Carpenter, MJ Ramakrishnan, V Hartwell, KJ Gray, KM AF Saladin, Michael E. McClure, Erin A. Baker, Nathaniel L. Carpenter, Matthew J. Ramakrishnan, Viswanathan Hartwell, Karen J. Gray, Kevin M. TI Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID NICOTINE REPLACEMENT THERAPY; COCAINE-SEEKING BEHAVIOR; LOCALLY WEIGHTED REGRESSION; MENSTRUAL-CYCLE; SEX-DIFFERENCES; FEMALE RATS; GENDER-DIFFERENCES; OVARIAN HORMONES; BIOLOGICAL BASIS; QUIT DATE AB Introduction: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. Methods: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. Results: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females. Conclusions: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medicationbased treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed. C1 [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Saladin, Michael E.; McClure, Erin A.; Carpenter, Matthew J.; Hartwell, Karen J.; Gray, Kevin M.] Med Univ S Carolina, Clin Neurosci Div, Charleston, SC 29425 USA. [Gray, Kevin M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Youth Div, Charleston, SC 29425 USA. [Carpenter, Matthew J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Baker, Nathaniel L.; Ramakrishnan, Viswanathan] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Hartwell, Karen J.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Subst Abuse Treatment Ctr, Charleston, SC USA. RP Saladin, ME (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, 77 President St,Room 224,MSC700, Charleston, SC 29425 USA. EM saladinm@musc.edu FU NIDA/ORWH/FDA [P50 DA016511]; Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women's Health; SouthCarolina Clinical and Translational Research (SCTR) Institute; academic home at the Medical University of South Carolina, through NIH [UL1 RR029882, UL1 TR000062] FX This research was supported by NIDA/ORWH/FDA grant P50 DA016511, Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women's Health, and by the SouthCarolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH grant numbers UL1 RR029882 and UL1 TR000062. Clinical Trials Registration clinicaltrials.gov identifier #NCT00664755. NR 61 TC 6 Z9 6 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2015 VL 17 IS 4 BP 398 EP 406 DI 10.1093/ntr/ntu262 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CH3CC UT WOS:000353903000004 PM 25762749 ER PT J AU Cho, JK Hyun, SH Choi, N Kim, MJ Padera, TP Choi, JY Jeong, HS AF Cho, Jae-Keun Hyun, Seung Hyup Choi, Nayeon Kim, Min-Ji Padera, Timothy P. Choi, Joon Young Jeong, Han-Sin TI Significance of Lymph Node Metastasis in Cancer Dissemination of Head and Neck Cancer SO TRANSLATIONAL ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; DISTANT METASTASES; PRIMARY TUMOR; SURVIVAL; RADIOTHERAPY; DISSECTION; OPERATIONS; EVALUATE AB Lymph node metastasis (LNM) in many solid cancers is a well-known prognostic factor; however, it has been debated whether regional LNM simply reflects tumor aggressiveness or is a source for further tumor dissemination. Similarly, the metastatic process in head and neck cancer (HNC) has not been fully evaluated. Thus, we aimed to investigate the relative significance of LNM in metastatic cascade of HNC using functional imaging of HNC patients and molecular imaging in in vivo models. First, we analyzed (18)Fluorodeoxyglucose positron emission tomography (PET) parameters of 117 patients with oral cancer. The primary tumor and nodal PET parameters were measured separately, and survival analyses were conducted on the basis of clinical and PET variables to identify significant prognostic factors. In multivariate analyses, we found that only the metastatic node PET values were significant. Next, we compared the relative frequency of lung metastasis in primary ear tumors versus lymph node (LN) tumors, and we tested the rate of lung metastasis in another animal model, in which each animal had both primary and LN tumors that were expressing different colors. As a result, LN tumors showed higher frequencies of lung metastasis compared to orthotopic primary tumors. In color-matched comparisons, the relative contribution to lung metastasis was higher in LN tumors than in primary tumors, although both primary and LN tumors caused lung metastases. In summary, tumors growing in the LN microenvironment spread to systemic sites more commonly than primary tumors in HNC, suggesting that the adequate management of LNM can reduce further systemic metastasis. C1 [Cho, Jae-Keun] Pusan Natl Univ, Dept Otorhinolaryngol Head & Neck Surg, Pusan 609735, South Korea. [Hyun, Seung Hyup; Choi, Joon Young] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Nucl Med, Seoul 135710, South Korea. [Choi, Nayeon; Jeong, Han-Sin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Seoul 135710, South Korea. [Kim, Min-Ji] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Biostat & Clin Epidemiol Ctr,Res Inst Future Med, Seoul 135710, South Korea. [Padera, Timothy P.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Padera, Timothy P.] Harvard Univ, Sch Med, Boston, MA USA. RP Jeong, HS (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, 81 Irwon Ro, Seoul 135710, South Korea. EM hansin.jeong@gmail.com RI Jeong, Han Sin/F-4597-2014; Choi, Joon Young/D-6140-2017; OI Padera, Timothy/0000-0002-3453-9384 FU Samsung Medical Center, Research Development grant [GL1-B2-291-1]; National Research Foundation of Korea (NRF) - Korea government (MEST) [2012R1A1A2040866]; KIST-SMC Translational Research Project; US NIH [DP2 OD008780] FX This work was supported by Samsung Medical Center, Research Development grant no. GL1-B2-291-1, National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) no. 2012R1A1A2040866, KIST-SMC Translational Research Project 2013 and US NIH DP2 OD008780. NR 31 TC 3 Z9 3 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD APR PY 2015 VL 8 IS 2 BP 119 EP 125 DI 10.1016/j.tranon.2015.03.001 PG 7 WC Oncology SC Oncology GA CH9RG UT WOS:000354373100006 PM 25926078 ER PT J AU Russell, FM Moore, CL Courtney, DM Kabrhel, C Smithline, HA Nordenholz, KE Richman, PB O'Neil, BJ Plewa, MC Beam, DM Mastouri, R Kline, JA AF Russell, Frances M. Moore, Christopher L. Courtney, D. Mark Kabrhel, Christopher Smithline, Howard A. Nordenholz, Kristen E. Richman, Peter B. O'Neil, Brian J. Plewa, Michael C. Beam, Daren M. Mastouri, Ronald Kline, Jeffrey A. TI Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY MAY 13-17, 2014 CL Dallas, TX SP Soc Acad Emergency Med ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; PULMONARY-HYPERTENSION; EMERGENCY-DEPARTMENT; TRICUSPID REGURGITATION; SLEEP-APNEA; CHEST-PAIN; MULTICENTER; MANAGEMENT; EMBOLISM; COPD AB Background: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. Methods: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. Results: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). Conclusion: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Russell, Frances M.; Beam, Daren M.; Kline, Jeffrey A.] Indiana Univ, Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Moore, Christopher L.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Courtney, D. Mark] Northwestern Univ, Dept Emergency Med, Evanston, IL USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Smithline, Howard A.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Nordenholz, Kristen E.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Richman, Peter B.] Texas A&M Hlth Sci Ctr, Dept Emergency Med, Corpus Christi, TX USA. [O'Neil, Brian J.] Wayne State Univ, Dept Emergency Med, Detroit, MI USA. [Plewa, Michael C.] Mercy St Vincent Mercy Med Ctr, Dept Emergency Med, Toledo, OH USA. [Mastouri, Ronald] Indiana Univ, Sch Med, Dept Internal Med, Div Cardiol, Indianapolis, IN 46202 USA. RP Russell, FM (reprint author), Indiana Univ, Sch Med, Dept Emergency Med, 720 Eskenazi Ave,Fifth Third Fac Off Bldg, Indianapolis, IN 46202 USA. EM framruss@iupui.edu; chris.moore@yale.edu; mcourtney@nmff.org; ckabrhel@partners.org; howard.smithline@bhs.org; Kristen.Nordenholz@ucdenver.edu; prichmanmdmba@gmail.com; boneil@med.wayne.edu; Michael_Plewa@mhsnr.org; dmbeam@iu.edu; ramastou@iu.edu; jefkline@iupui.edu OI Kabrhel, Christopher/0000-0002-8699-7176 FU NHLBI NIH HHS [2R42HL074415-02A1, R41 HL074415, R42 HL074415, 5K23HL0774, 5R42HL074415-03] NR 23 TC 1 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD APR PY 2015 VL 33 IS 4 BP 542 EP 547 DI 10.1016/j.ajem.2015.01.026 PG 6 WC Emergency Medicine SC Emergency Medicine GA CG6BP UT WOS:000353380800014 PM 25769797 ER PT J AU Bellmunt, J Mullane, SA Werner, L Fay, AP Callea, M Leow, JJ Taplin, ME Choueiri, TK Hodi, FS Freeman, GJ Signoretti, S AF Bellmunt, J. Mullane, S. A. Werner, L. Fay, A. P. Callea, M. Leow, J. J. Taplin, M. E. Choueiri, T. K. Hodi, F. S. Freeman, G. J. Signoretti, S. TI Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE urothelial carcinoma; PD-1; PD-L1; immunotherapy; prognosis; overall survival ID BACILLUS-CALMETTE-GUERIN; CD8(+) T-LYMPHOCYTES; INTEGRATIVE ANALYSIS; PROGNOSTIC-FACTORS; BLADDER-CARCINOMA; IMMUNE-MECHANISMS; B7-H1 EXPRESSION; LUNG-CANCER; IN-SITU; IMMUNOTHERAPY AB Background: Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway negatively regulates T-cell-mediated responses. The prognostic impact of PD-L1 expression needs to be defined in urothelial carcinoma (UC). Patients and methods: Formalin-fixed paraffin-embedded tumor samples from 160 patients with UC were retrieved. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). PD-L1 positivity on tumor cell membrane was defined as >= 5% of tumor cell membrane staining. The extent of tumor-infiltrating mononuclear cells (TIMCs) as well as PD-L1 expression on TIMCs was scored from 0 to 4. A score of 2, 3, or 4 was considered PD-L1-positive. Clinico-pathological variables were documented. The Cox regression model was used to assess the association of PD-L1 expression with overall survival (OS) in patients who developed metastases. Results: TIMCs were present in 143 of the 160 patient samples. Out of 160 samples, 32 (20%) had positive PD-L1 expression in tumor cell membrane. Out of 143 samples with TIMCs, 58 (40%) had positive PD-L1 expression in TIMCs. Smoking history, prior BCG use and chromosome 9 loss did not correlate with PD-L1 expression in either tumor cell membrane or TIMCs. PD-L1 positivity was not different between non-invasive or invasive UC. In patients who developed metastases (M1) and were treated with systemic therapy (n = 100), PD-L1 positivity on tumor cell membrane was seen in 14% of patients and did not correlate with OS (P = 0.45). Out of 89 M1 patients who had evaluable PD-L1 on TIMCs, PD-L1 expression was seen in 33% of patients and was significantly associated with longer OS on multivariate analysis (P = 0.0007). Conclusion: PD-L1 is widely expressed in tumor cell membrane and TIMCs in UC. PD-L1 in tumor cells was not predictive of OS. However, positive PD-L1 expression in TIMCs was significantly associated with longer survival in those patients who developed metastases. C1 [Bellmunt, J.; Mullane, S. A.; Werner, L.; Fay, A. P.; Leow, J. J.; Taplin, M. E.; Choueiri, T. K.; Signoretti, S.] Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA 02215 USA. [Bellmunt, J.; Taplin, M. E.; Choueiri, T. K.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Bellmunt, J.; Taplin, M. E.; Choueiri, T. K.; Hodi, F. S.; Freeman, G. J.; Signoretti, S.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. [Bellmunt, J.; Mullane, S. A.; Fay, A. P.; Taplin, M. E.; Choueiri, T. K.; Hodi, F. S.; Freeman, G. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Callea, M.; Signoretti, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hodi, F. S.] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02215 USA. RP Bellmunt, J (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave DANA 1230, Boston, MA 02215 USA. EM joaquim_bellmunt@dfci.harvard.edu FU Retired Professional Fire Fighters Cancer Fund; Whole Foods Marker Charity Golf Classic for Bladder Cancer Research in memory of Chris Snell FX This study was possible thanks to a grant from the Retired Professional Fire Fighters Cancer Fund and a private donation of the Whole Foods Marker Charity Golf Classic for Bladder Cancer Research in memory of Chris Snell. No grant number applied. NR 30 TC 29 Z9 30 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2015 VL 26 IS 4 BP 812 EP 817 DI 10.1093/annonc/mdv009 PG 6 WC Oncology SC Oncology GA CH2BI UT WOS:000353828700031 PM 25600565 ER PT J AU Cabrera-Serrano, M Ghaoui, R Ravenscroft, G Johnsen, RD Davis, MR Corbett, A Reddel, S Sue, CM Liang, C Waddell, LB Kaur, S Lek, M North, KN MacArthur, DG Lamont, PJ Clarke, NF Laing, NG AF Cabrera-Serrano, Macarena Ghaoui, Roula Ravenscroft, Gianina Johnsen, Russell D. Davis, Mark R. Corbett, Alastair Reddel, Stephen Sue, Carolyn M. Liang, Christina Waddell, Leigh B. Kaur, Simranpreet Lek, Monkol North, Kathryn N. MacArthur, Daniel G. Lamont, Phillipa J. Clarke, Nigel F. Laing, Nigel G. TI Expanding the phenotype of GMPPB mutations SO BRAIN LA English DT Article DE GMPPB; dystroglycanopathies; alpha-dystroglycan; limb-girdle muscular dystrophy; rhabdomyolysis ID MUSCULAR-DYSTROPHIES; ALPHA-DYSTROGLYCAN; GENOTYPE AB Mutations of GDP mannose pyrophosphorylase B (GMPPB) cause an early-onset muscular dystrophy and associated extra-muscular features. Cabrera-Serrano et al. broaden the clinical spectrum of this dystroglycanopathy by identifying patients with a milder phenotype presenting in adolescence or adulthood, including one with isolated episodes of rhabdomyolysis.Dystroglycanopathies are a heterogeneous group of diseases with a broad phenotypic spectrum ranging from severe disorders with congenital muscle weakness, eye and brain structural abnormalities and intellectual delay to adult-onset limb-girdle muscular dystrophies without mental retardation. Most frequently the disease onset is congenital or during childhood. The exception is FKRP mutations, in which adult onset is a common presentation. Here we report eight patients from five non-consanguineous families where next generation sequencing identified mutations in the GMPPB gene. Six patients presented as an adult or adolescent-onset limb-girdle muscular dystrophy, one presented with isolated episodes of rhabdomyolysis, and one as a congenital muscular dystrophy. This report expands the phenotypic spectrum of GMPPB mutations to include limb-girdle muscular dystrophies with adult onset with or without intellectual disability, or isolated rhabdomyolysis. C1 [Cabrera-Serrano, Macarena; Ravenscroft, Gianina; Laing, Nigel G.] Univ Western Australia, Med Res Ctr, Harry Perkins Inst Med Res, Perth, WA 6009, Australia. [Cabrera-Serrano, Macarena] Univ Seville, CSIC, Inst Biomed Sevilla, Hosp Univ Virgen del Rocio, Seville, Spain. [Ghaoui, Roula; Waddell, Leigh B.; Kaur, Simranpreet; Lek, Monkol; North, Kathryn N.; Clarke, Nigel F.] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia. [Ghaoui, Roula; Waddell, Leigh B.; Lek, Monkol; Clarke, Nigel F.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Ghaoui, Roula; Sue, Carolyn M.; Liang, Christina] Royal N Shore Hosp, Dept Neurol, Sydney, NSW, Australia. [Johnsen, Russell D.] Murdoch Univ, Ctr Comparat Genom, Perth, WA, Australia. [Davis, Mark R.] Pathwest Lab Med WA, Dept Diagnost Genom, Perth, WA, Australia. [Corbett, Alastair; Reddel, Stephen] Concord Repatriat Gen Hosp, Dept Neurol, Sydney, NSW, Australia. [Corbett, Alastair; Reddel, Stephen] Sydney Med Sch, Sydney, NSW, Australia. [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [North, Kathryn N.] Univ Melbourne, Dept Paediat, Melbourne, Vic 3010, Australia. [Lamont, Phillipa J.] Royal Perth Hosp, Dept Neurol, Neurogenet Unit, Perth, WA 6001, Australia. RP Cabrera-Serrano, M (reprint author), Univ Western Australia, Med Res Ctr, Harry Perkins Inst Med Res, Nedlands, WA 6009, Australia. EM Macarena.cabrera@uwa.edu.au RI IBIS, FISIOLOGIA/O-9485-2015; North, Kathryn/K-6476-2012 OI North, Kathryn/0000-0003-0841-8009 FU Fundacion Alfonso Martin Escudero; Australian National Health and Medical Research Council (NHMRC) [APP1002147, APP1055295, APP1031893, APP1022707, APP1035955, APP 1008433, APP1035828] FX M.C.S. has been supported by Fundacion Alfonso Martin Escudero. This project has been supported by Australian National Health and Medical Research Council (NHMRC) grants APP1002147 and APP1055295 (N.G.L), APP1031893 & APP1022707 (K.N.N., N.G.L., N.F.C.), APP1035955 (G.R.), APP 1008433 (C.M.S.) and APP1035828 (N.F.C.). NR 16 TC 9 Z9 9 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD APR 1 PY 2015 VL 138 BP 836 EP 844 DI 10.1093/brain/awv013 PN 4 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG7XZ UT WOS:000353522100013 PM 25681410 ER PT J AU Mainero, C Louapre, C Govindarajan, ST Gianni, C Nielsen, AS Cohen-Adad, J Sloane, J Kinkel, RP AF Mainero, Caterina Louapre, Celine Govindarajan, Sindhuja T. Gianni, Costanza Nielsen, A. Scott Cohen-Adad, Julien Sloane, Jacob Kinkel, Revere P. TI A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging SO BRAIN LA English DT Article DE multiple sclerosis; subpial demyelination; quantitative T-2*; 7 T MRI; sulci; gyri ID MAGNETIZATION-TRANSFER RATIO; SURFACE-BASED ANALYSIS; CEREBRAL-CORTEX; MENINGEAL INFLAMMATION; SUBPIAL DEMYELINATION; FIELD-STRENGTH; HUMAN BRAIN; LESIONS; IRON; MRI AB Mainero et al. use 7 Tesla MR quantitative T-2* imaging to map intracortical laminar pathology in patients with multiple sclerosis. A gradient of cortical pathology is seen across disease stages in association with worsening disability, suggesting that a pathological process driven from the pial surface contributes to disease progression.We used a surface-based analysis of T-2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T-2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T-2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (a parts per thousand currency sign3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (a parts per thousand yen4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T-2* maps were registered to anatomical cortical surfaces for sampling T-2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T-2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T-2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T-2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T-2* was compared with patients' normal-appearing cortical grey matter T-2* (paired t-test) and with mean cortical T-2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T-2*, consistent with cortical myelin and iron loss. In early disease, T-2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T-2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T-2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10(-10) and P < 10(-7)), and mean cortical T-2* in controls (P < 10(-5) and P < 10(-6)). In secondary progressive multiple sclerosis, T-2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T-2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T-2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface. C1 [Mainero, Caterina; Louapre, Celine; Govindarajan, Sindhuja T.; Gianni, Costanza; Cohen-Adad, Julien] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mainero, Caterina; Louapre, Celine; Gianni, Costanza; Nielsen, A. Scott; Sloane, Jacob; Kinkel, Revere P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nielsen, A. Scott; Sloane, Jacob; Kinkel, Revere P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nielsen, A. Scott] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Cohen-Adad, Julien] Polytech Montreal, Inst Biomed Engn, Montreal, PQ, Canada. [Kinkel, Revere P.] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Mainero, C (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA. EM caterina@nmr.mgh.harvard.edu OI Gianni, Costanza/0000-0002-4018-169X FU National multiple sclerosis Society [NMSS 4281-RG-A1]; Claflin Award; NIH [R01NS078322-01-A1]; National Center for Research Resources [NCRR P41-RR14075]; US Army [W81XWH-13-1-0122]; ARSEP; FISM [2012/B/4]; NMSS [1892-FG-A1, 1770-FP-A1]; Harvard Medical School SCSP [NH 1 KL2 RR025757-0] FX This work was supported by a grant of the National multiple sclerosis Society (NMSS 4281-RG-A1), the Claflin Award, and partly by NIH R01NS078322-01-A1, the National Center for Research Resources (NCRR P41-RR14075), and US Army W81XWH-13-1-0122.; Dr Louapre was supported by a fellowship from ARSEP; Dr Gianni' was supported by FISM training fellowship 2012/B/4; Dr Cohen Adad received support from NMSS 1892-FG-A1; Dr Nielsen received fellowship support through the NMSS 1770-FP-A1 and Harvard Medical School SCSP (NH 1 KL2 RR025757-0). NR 47 TC 22 Z9 22 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD APR 1 PY 2015 VL 138 BP 932 EP 945 DI 10.1093/brain/awv011 PN 4 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG7XZ UT WOS:000353522100020 PM 25681411 ER PT J AU Huijbers, W Mormino, EC Schultz, AP Wigman, S Ward, AM Larvie, M Amariglio, RE Marshall, GA Rentz, DM Johnson, KA Sperling, RA AF Huijbers, Willem Mormino, Elizabeth C. Schultz, Aaron P. Wigman, Sarah Ward, Andrew M. Larvie, Mykol Amariglio, Rebecca E. Marshall, Gad A. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. TI Amyloid-beta deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression SO BRAIN LA English DT Article DE amyloid deposition; MCI; hippocampal activation; functional MRI; clinical progression ID PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; OLDER-ADULTS; LIFE-SPAN; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; BRAIN ACTIVATION; FMRI ACTIVATION; FUNCTIONAL MRI; GENETIC RISK AB In a 3-year longitudinal study, Huijbers et al. observe increased hippocampal activation, faster rates of hippocampal atrophy, and clinical progression in patients with mild cognitive impairment with elevated levels of amyloid-beta. Amyloid-beta accumulation likely contributes to abnormal neuronal activity on the trajectory towards Alzheimer's disease dementia.Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity-consistent with findings in genetic at-risk populations-and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-beta, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloid-beta deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-beta status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-beta positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-beta negative patients with mild cognitive impairment. Longitudinally, amyloid-beta positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model, amyloid-beta status, hippocampal activation, and hippocampal volume independently predicted clinical progression. These results indicate that amyloid-beta positive patients with mild cognitive impairment are more likely on a path towards Alzheimer's disease dementia than amyloid-beta negative patients. Increased hippocampal activity is discussed in relation to neuronal compensation and/or amyloid-beta induced excitoxicity. C1 [Huijbers, Willem; Mormino, Elizabeth C.; Wigman, Sarah; Ward, Andrew M.; Amariglio, Rebecca E.; Marshall, Gad A.; Rentz, Dorene M.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol,Med Sch, Boston, MA 02115 USA. [Huijbers, Willem; Wigman, Sarah; Ward, Andrew M.; Larvie, Mykol; Amariglio, Rebecca E.; Marshall, Gad A.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Neurol,Med Sch, Charlestown, MA USA. [Mormino, Elizabeth C.; Schultz, Aaron P.; Larvie, Mykol; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Ward, Andrew M.] Univ Calif Berkeley, Dept Mol & Cell Biol, Helen Willis Neurosci Inst, Berkeley, CA 94720 USA. RP Huijbers, W (reprint author), Martinos Ctr Biomed imaging, 149 13th St, Charlestown, MA 02129 USA. EM w.huijbers@gmail.com OI Ward, Andrew/0000-0001-6948-4814 FU European Molecular Biology Organization [ALTF 318-2011]; National Institutes of Health [F32 AG044054, K23 AG033634, K24 AG035007, R01 AG027435, P01AG036694, P50AG00513421]; Alzheimer's Association [IIRG-06-27374]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health FX This research was supported by the European Molecular Biology Organization: ALTF 318-2011 (W.H.), the National Institutes of Health: F32 AG044054 (E.M.), K23 AG033634 (G.M.), K24 AG035007 (R.S.), K23 AG033634 (G.M.), R01 AG027435 (R.S.), P01AG036694 (R.S.), P50AG00513421 (R.S.) and the Alzheimer's Association: IIRG-06-27374 (R.S.) and a philanthropic gift by Foundation for Neurologic Diseases (W.H./R.S.). This research was carried out in part at the Athinoula A. Martinos Centre for Biomedical Imaging, using resources provided by the Centre for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National institutes of Health. NR 88 TC 21 Z9 21 U1 0 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD APR 1 PY 2015 VL 138 BP 1023 EP 1035 DI 10.1093/brain/awv007 PN 4 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG7XZ UT WOS:000353522100026 PM 25678559 ER PT J AU Ringman, JM Liang, LJ Zhou, Y Vangala, S Teng, E Kremen, S Wharton, D Goate, A Marcus, DS Farlow, M Ghetti, B McDade, E Masters, CL Mayeux, RP Rossor, M Salloway, S Schofield, PR Cummings, JL Buckles, V Bateman, R Morris, JC AF Ringman, John M. Liang, Li-Jung Zhou, Yan Vangala, Sitaram Teng, Edmond Kremen, Sarah Wharton, David Goate, Alison Marcus, Daniel S. Farlow, Martin Ghetti, Bernardino McDade, Eric Masters, Colin L. Mayeux, Richard P. Rossor, Martin Salloway, Stephen Schofield, Peter R. Cummings, Jeffrey L. Buckles, Virginia Bateman, Randall Morris, John C. CA Dominantly Inherited Alzheimer TI Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network SO BRAIN LA English DT Article DE behaviour; depression; Alzheimer; prodromal; familial ID MILD COGNITIVE IMPAIRMENT; PRESENILIN-1 MUTATION CARRIERS; DEPRESSIVE SYMPTOMS; NEUROPSYCHIATRIC SYMPTOMS; OLDER-ADULTS; DEMENTIA; PROGRESSION; ONSET; ASSOCIATION; DECLINE AB Ringman et al. characterize behavioural changes in individuals with preclinical and early familial Alzheimer's disease. Significant behavioural changes do not occur prior to cognitive decline but, in common with late-onset Alzheimer's disease, increased rates of depression, anxiety, apathy and other behavioural changes are seen early in manifest familial disease.Prior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer's disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer's disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer's disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer's disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer's disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26-0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P < 0.0001), disinhibition (16% versus 2%, P = 0.009), irritability (48% versus 9%, P = 0.0001), sleep changes (28% versus 7%, P = 0.003), and agitation (24% versus 6%, P = 0.008) were more common and the degree of self-rated depression more severe (mean Geriatric Depression Scale score of 2.8 versus 1.4, P = 0.006) in mildly symptomatic mutation carriers relative to non-carriers. Anxiety, appetite changes, delusions, and repetitive motor activity were additionally more common in overtly impaired mutation carriers. Similar to studies of late-onset Alzheimer's disease, we demonstrated increased rates of depression, apathy, and other behavioural symptoms in the mildly symptomatic, prodromal phase of autosomal dominant Alzheimer's disease that increased with disease severity. We did not identify any increased psychopathology in mutation carriers over non-carriers during the presymptomatic stage, suggesting these symptoms result when a threshold of neurodegeneration is reached rather than as life-long qualities. Unexpectedly, we found lower rates of depressive symptoms in cognitively asymptomatic mutation carriers. C1 [Ringman, John M.; Zhou, Yan; Teng, Edmond; Kremen, Sarah; Wharton, David] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. [Liang, Li-Jung; Vangala, Sitaram] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Teng, Edmond] VA Greater Los Angeles Healthcare Syst, Neurobehav Serv, GRECC, Los Angeles, CA 90095 USA. [Goate, Alison] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Marcus, Daniel S.; Buckles, Virginia; Bateman, Randall; Morris, John C.] Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63108 USA. [Farlow, Martin] Indiana Univ, Dept Neurol, Indianapolis, IN 46202 USA. [Ghetti, Bernardino] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [McDade, Eric] Univ Pittsburgh, Sch Med, Alzheimer Dis Res Ctr, Pittsburgh, PA 15213 USA. [Masters, Colin L.] Univ Melbourne, Florey Inst, Parkville, Vic 3010, Australia. [Mayeux, Richard P.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Rossor, Martin] UCL, Inst Neurol, Dementia Res Ctr, Dept Neurodegenerat, London WC1 3BG, England. [Salloway, Stephen] Brown Univ, Butler Hosp, Providence, RI 02906 USA. [Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Cummings, Jeffrey L.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV 89106 USA. RP Ringman, JM (reprint author), USC Dept Neurol, Memory & Aging Ctr, 1540 Alcazar St,CHP215, Los Angeles, CA 90033 USA. EM jringman@mednet.ucla.edu FU Dominantly Inherited Alzheimer Network (DIAN) - National Institute on Aging (NIA) [U19AG032438]; UCLA Alzheimer's Disease Research Center Grant [P50 AG-16570]; UCLA Clinical Translational Research Institute [1UL1-RR033176]; Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarker Development; NIHR Queen Square Dementia BRU FX Study supported by: Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA). Further support for this work comes from the UCLA Alzheimer's Disease Research Center Grant P50 AG-16570, the UCLA Clinical Translational Research Institute 1UL1-RR033176, the Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarker Development, and the NIHR Queen Square Dementia BRU. NR 36 TC 13 Z9 13 U1 5 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD APR 1 PY 2015 VL 138 BP 1036 EP 1045 DI 10.1093/brain/awv004 PN 4 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG7XZ UT WOS:000353522100027 PM 25688083 ER PT J AU Bhalla, P Forrest, GN Gershon, M Zhou, Y Chen, J LaRussa, P Steinberg, S Gershon, AA AF Bhalla, Preeti Forrest, Graeme N. Gershon, Michael Zhou, Yan Chen, Jason LaRussa, Philip Steinberg, Sharon Gershon, Anne A. TI Disseminated, Persistent, and Fatal Infection Due to the Vaccine Strain of Varicella-Zoster Virus in an Adult Following Stem Cell Transplantation SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE zoster; vOka; varicella; vaccine; granulomas ID KILLER T-CELLS; HERPES-ZOSTER; CUTANEOUS REACTIONS; NERVOUS-SYSTEM; SAFETY PROFILE; PATIENT; DEFICIENCY; CHILD; COMPLICATIONS; GRANULOMAS AB Live attenuated varicella vaccine is recommended for healthy individuals who are susceptible to varicella. Although the vaccine is safe, effective, and used worldwide, serious adverse events have been reported, mainly in immunocompromised patients who subsequently recovered. Here, we describe the fatality of an immunocompromised patient who received the varicella vaccine. His medical history provides a cautionary lens through which to view the decision of when vaccination is appropriate. A middle-aged man with non-Hodgkin lymphoma received chemotherapy and a stem cell transplant. He was vaccinated 4 years post-transplantation, despite diagnosis of a new low-grade lymphoma confined to the lymph nodes. Within 3 months of vaccination, he developed recurrent rashes with fever, malaise, weakness, hepatitis, weight loss, and renal failure. The syndrome was eventually determined to be associated with persistent disseminated zoster caused by the vaccine virus. This case illustrates a circumstance when a live viral vaccine should not be used. C1 [Bhalla, Preeti; Forrest, Graeme N.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Forrest, Graeme N.] Portland VA Med Ctr, Portland, OR USA. [Gershon, Michael; Zhou, Yan; Chen, Jason] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA. [LaRussa, Philip; Steinberg, Sharon; Gershon, Anne A.] Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. RP Gershon, AA (reprint author), Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. EM aag1@cumc.columbia.edu FU NIDDK NIH HHS [R01 DK093094] NR 40 TC 11 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2015 VL 60 IS 7 BP 1068 EP 1074 DI 10.1093/cid/ciu970 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0MH UT WOS:000353714000013 PM 25452596 ER PT J AU Ross, EL Weinstein, MC Schackman, BR Sax, PE Paltiel, AD Walensky, RP Freedberg, KA Losina, E AF Ross, Eric L. Weinstein, Milton C. Schackman, Bruce R. Sax, Paul E. Paltiel, A. David Walensky, Rochelle P. Freedberg, Kenneth A. Losina, Elena TI The Clinical Role and Cost-Effectiveness of Long-Acting Antiretroviral Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV/AIDS; long-acting antiretroviral therapy; cost-effectiveness; modeling ID UNITED-STATES; HIV DISEASE; ADHERENCE; HEALTH; REGIMENS; CARE; RILPIVIRINE; GSK1265744; RETENTION; EFAVIRENZ AB Background. Long-acting antiretroviral therapy (LA-ART) is currently under development and could improve outcomes for human immunodeficiency virus (HIV)-infected individuals with poor daily ART adherence. Methods. We used a computer simulation model to evaluate the cost-effectiveness of 3 LA-ART strategies vs daily oral ART for all: (1) LA-ART for patients with multiple ART failures; (2) second-line LA-ART for those failing first-line therapy; and (3) first-line LA-ART for ART-naive patients. We calculated the maximum annual cost of LA-ART at which each strategy would be cost-effective at a willingness to pay of $100 000 per quality-adjusted life-year. We assumed HIV RNA suppression on daily ART ranged from 0% to 91% depending on adherence, vs 91% suppression on LA-ART regardless of daily ART adherence. In sensitivity analyses, we varied adherence, efficacy of LA-ART and daily ART, and loss to follow-up. Results. Relative to daily ART, LA-ART increased overall life expectancy by 0.15-0.24 years, and by 0.51-0.89 years among poorly adherent patients, depending on the LA-ART strategy. LA-ART after multiple failures became cost-effective at an annual drug cost of $48 000; in sensitivity analysis, this threshold varied from $40 000-$70 000. Second-line LA-ART and first-line LA-ART became cost-effective at an annual drug cost of $26 000-$31 000 and $24 000-$27 000, vs $28 000 and $25 000 for current second-line and first-line regimens. Conclusions. LA-ART could improve survival of HIV patients, especially those with poor daily ART adherence. At an annual cost of $40 000-$70 000, LA-ART will offer good value for patients with multiple prior failures. To be a viable option for first-or second-line therapy, however, its cost must approach that of currently available regimens. C1 [Ross, Eric L.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ross, Eric L.; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY USA. [Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. [Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Sax, Paul E.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Losina, E (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM elosina@partners.org FU National Institutes of Health (NIH) [R37AI042006] FX Research reported in this publication was supported by the National Institutes of Health (NIH) under award number R37AI042006. NR 41 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2015 VL 60 IS 7 BP 1102 EP 1110 DI 10.1093/cid/ciu1159 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0MH UT WOS:000353714000019 PM 25583979 ER PT J AU Siedner, MJ Ng, CK Bassett, IV Katz, IT Bangsberg, DR Tsai, AC AF Siedner, Mark J. Ng, Courtney K. Bassett, Ingrid V. Katz, Ingrid T. Bangsberg, David R. Tsai, Alexander C. TI Trends in CD4 Count at Presentation to Care and Treatment Initiation in Sub-Saharan Africa, 2002-2013: A Meta-analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV/AIDS; sub-Saharan Africa; antiretroviral therapy; linkage to care; meta-analysis ID COMBINATION ANTIRETROVIRAL THERAPY; HIV CARE; SOUTH-AFRICA; IMPROVED SURVIVAL; INCOME COUNTRIES; LIFE EXPECTANCY; CELL COUNT; SCALE-UP; PREVENTION; UGANDA AB Background. Both population- and individual-level benefits of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) are contingent on early diagnosis and initiation of therapy. We estimated trends in disease status at presentation to care and at ART initiation in sub-Saharan Africa. Methods. We searched PubMed for studies published January 2002-December 2013 that reported CD4 cell count at presentation or ART initiation among adults in sub-Saharan Africa. We abstracted study sample size, year(s), and mean CD4 count. A random-effects meta-regression model was used to obtain pooled estimates during each year of the observation period. Results. We identified 56 articles reporting CD4 count at presentation (N = 295 455) and 71 articles reporting CD4 count at ART initiation (N = 549 702). The mean estimated CD4 count in 2002 was 251 cells/mu L at presentation and 152 cells/mu L at ART initiation. During 2002-2013, neither CD4 count at presentation (beta = 5.8 cells/year; 95% confidence interval [CI], -10.7 to 22.4 cells/year), nor CD4 count at ART initiation (beta = -1.1 cells/year; 95% CI, -8.4 to 6.2 cells/year) increased significantly. Excluding studies of opportunistic infections or prevention of mother-to-child transmission did not alter our findings. Among studies conducted in South Africa (N = 14), CD4 count at presentation increased by 39.9 cells/year (95% CI, 9.2-70.2 cells/year; P = .02), but CD4 count at ART initiation did not change. Conclusions. CD4 counts at presentation to care and at ART initiation in sub-Saharan Africa have not increased over the past decade. Barriers to presentation, diagnosis, and linkage to HIV care remain major challenges that require attention to optimize population-level benefits of ART. C1 [Siedner, Mark J.; Ng, Courtney K.; Katz, Ingrid T.; Bangsberg, David R.; Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Siedner, Mark J.; Bassett, Ingrid V.; Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Siedner, Mark J.; Bassett, Ingrid V.; Katz, Ingrid T.; Bangsberg, David R.; Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Katz, Ingrid T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bangsberg, David R.; Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St, Boston, MA 02114 USA. EM msiedner@mgh.havard.edu OI Tsai, Alexander/0000-0001-6397-7917 FU US National Institutes of Health [K23MH099916, K23MH096620, K23MH097667, R01MH090326] FX The authors received no specific funding for this study. The authors acknowledge salary support from the US National Institutes of Health (grant numbers K23MH099916, K23MH096620, K23MH097667, and R01MH090326). NR 37 TC 50 Z9 50 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2015 VL 60 IS 7 BP 1120 EP 1127 DI 10.1093/cid/ciu1137 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0MH UT WOS:000353714000021 PM 25516189 ER PT J AU Manian, F AF Manian, Farrin TI Surgical Site Infections and Postoperative Factors Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Manian, F (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,Ste 503-B, Boston, MA 02114 USA. EM farrinman@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2015 VL 60 IS 7 BP 1137 EP U202 DI 10.1093/cid/ciu1142 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0MH UT WOS:000353714000027 PM 25516186 ER PT J AU van Koeverden, I Blanc, PD Bowler, RP Arjomandi, M AF van Koeverden, Ian Blanc, Paul D. Bowler, Russell P. Arjomandi, Mehrdad TI Secondhand Tobacco Smoke and COPD Risk in Smokers: A COPDGene Study Cohort Subgroup Analysis SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE COPD; secondhand tobacco smoke; occupational exposure; job exposure matrix; cigarette smoking; work-related ID OBSTRUCTIVE PULMONARY-DISEASE; JOB-EXPOSURE MATRIX; OCCUPATIONAL-EXPOSURE; BURDEN; ADULTS; ASTHMA; OUTCOMES; DESIGN; IMPACT; FUMES AB Background: Exposure to secondhand tobacco smoke (SHS) can be a risk factor for chronic obstructive pulmonary disease (COPD), but its role among relatively heavy smokers with potential co-exposure to workplace vapors, gas, dust, and fumes (VGDF) has not been studied. Methods: To estimate the contribution of SHS exposure to COPD risk, taking into account smoking effects and work-related exposures to VGDF, we quantified SHS based on survey responses for 1400 ever-employed subjects enrolled in the COPDGene study, all current or former smokers with or without COPD. Occupational exposures to VGDF were quantified based on a job exposure matrix. The associations between SHS and COPD were tested in multivariate logistic regression analyses adjusted for age, sex, VGDF exposure, and cumulative smoking. Results and Discussion: Exposures to SHS at work and at home during adulthood were associated with increased COPD risk: odds ratio (OR) = 1.12 (95% confidence interval [CI]: 1.02-1.23; p = 0.01) and OR = 1.09 (95% CI: 1.00-1.18; p = 0.04) per 10 years of exposure adjusted for smoking and other covariates, respectively. In addition, subjects with employment histories likely to entail exposure to VGDF were more likely to have COPD: OR = 1.52 (95% CI: 1.16-1.98; p < 0.01) (adjusted for other covariates). While adult home SHS COPD risk was attenuated among the heaviest smokers within the cohort, workplace SHS and job VGDF risks persisted in that stratum. Conclusion: Among smokers all with at least 10 pack-years, adult home and work SHS exposures and occupational VGDF exposure are all associated with COPD. C1 [van Koeverden, Ian] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [van Koeverden, Ian; Arjomandi, Mehrdad] San Francisco VA Med Ctr, Pulm Res Grp, San Francisco, CA USA. [Blanc, Paul D.] Univ Calif San Francisco, Dept Med, Div Occupat & Environm Med, San Francisco, CA 94121 USA. [Blanc, Paul D.; Arjomandi, Mehrdad] Univ Calif San Francisco, Dept Med, Div Pulm Crit Care Allergy & Immunol & Sleep Med, San Francisco, CA 94121 USA. [Bowler, Russell P.] Natl Jewish Hlth, Denver, CO USA. RP Arjomandi, M (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Pulm Crit Care Allergy & Immunol & Sleep Med, Bldg 203,Room 3A-128,Mailstop 111-D, San Francisco, CA 94121 USA. EM mehrdad.arjomandi@ucsf.edu FU NHLBI [U01 HL08-9856, U01 HL08-9897, K23 HL08-3099]; NCRR/HIH [UL1 RR025780]; Butcher Foundation; Flight Attendants Medical Research Institute (FAMRI) FX We would like to thank Dr. John Hokanson from University of Colorado Health Sciences with help in preparation of manuscript. Authors' contributions were as follows. Conceived and designed the experiment: RB. Collected data: RB. Designed analytical approach: MA, PB. Analyzed and interpreted the data: IvK, MA, PB. Wrote the manuscript: IvK, MA. Provided feedback on analyses and manuscript: PB, RB. Guarantor of the manuscript: MA, RB. The authors do not have any conflict of interest to disclose. This study was supported by NHLBI (U01 HL08-9856, U01 HL08-9897, Arjomandi K23 HL08-3099), NCRR/HIH (UL1 RR025780), the Butcher Foundation, and the Flight Attendants Medical Research Institute (FAMRI). The sponsors of the study had no role in the design and conduct of this study. NR 31 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 EI 1541-2563 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD APR PY 2015 VL 12 IS 2 BP 182 EP 189 DI 10.3109/15412555.2014.922173 PG 8 WC Respiratory System SC Respiratory System GA CH3JB UT WOS:000353925900010 ER PT J AU Neagu, MR Raibagkar, P Lyons, JL Klein, JP AF Neagu, Martha R. Raibagkar, Pooja Lyons, Jennifer L. Klein, Joshua P. TI Imaging in Neurologic Infections II: Fungal and Viral Diseases SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Imaging; Nervous system; Infection; Magnetic resonance imaging; Computed tomography; Encephalitis ID CENTRAL-NERVOUS-SYSTEM; COCCIDIOIDAL MENINGITIS; VARICELLA-ZOSTER; ELSBERG-SYNDROME; BRAIN; ASPERGILLOSIS; ENCEPHALITIS; PATIENT AB Infections of the nervous system have a significant impact on global mortality and morbidity. These infections are medical emergencies that are frequently diagnostically challenging. Incorporation of neuroimaging can be essential for early diagnosis and initiation of proper treatment. In this second part of this two-part review, we focus on diagnostic imaging features of selected fungal and viral nervous system infections. C1 [Neagu, Martha R.; Raibagkar, Pooja; Lyons, Jennifer L.; Klein, Joshua P.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Neagu, Martha R.; Raibagkar, Pooja; Lyons, Jennifer L.; Klein, Joshua P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Neagu, Martha R.; Raibagkar, Pooja] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Klein, Joshua P.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Klein, JP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jpklein@partners.org FU AAN Continuum FX Pooja Raibagkar and Martha Neagu have no conflicts of interest. Joshua Klein served as a board member for the American Society of Neuroimaging, received an Associate Editor stipend from the Journal of Neuroimaging, received honoraria from the American Academy of Neurology and honoraria from the Neurological Society of Pune, India, and received payment for manuscript preparation from the AAN Continuum journal and royalties from the Adams and Victor's Principles of Neurology textbook, 10th edition (McGraw-Hill). Jennifer Lyons received honoraria from Springer for working as a section editor. NR 31 TC 0 Z9 0 U1 1 U2 2 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 APR PY 2015 VL 17 IS 4 AR 15 DI 10.1007/s11908-015-0474-9 PG 11 WC Infectious Diseases SC Infectious Diseases GA CG7WB UT WOS:000353515800006 ER PT J AU Zeng, C Long, XY Cotten, JF Forman, SA Solt, K Faingold, CL Feng, HJ AF Zeng, Chang Long, Xiaoyan Cotten, Joseph F. Forman, Stuart A. Solt, Ken Faingold, Carl L. Feng, Hua-Jun TI Fluoxetine prevents respiratory arrest without enhancing ventilation in DBA/1 mice SO EPILEPSY & BEHAVIOR LA English DT Article DE Ventilation; Seizure-induced respiratory arrest; SUDEP; SSRI; Breathing stimulants ID SUDDEN UNEXPECTED DEATH; SEROTONIN REUPTAKE INHIBITORS; ICTAL HYPOXEMIA; RISK-FACTORS; EPILEPSY; NEURONS; RATS; SUDEP; SEVERITY; DOXAPRAM AB Sudden unexpected death in epilepsy (SUDEP) is a fatal epileptic event. DBA/1 mice are a relevant animal model for the study of SUDEP, as these mice exhibit seizure-induced respiratory arrest (S-IRA) leading to death, which has been observed in patients with witnessed SUDEP. Fluoxetine, a selective serotonin (5-hydroxytryptamine or 5-HT) reuptake inhibitor (SSRI), reduces S-IRA in DBA/1 mice. Given that DBA/1 mice with S-IRA can be resuscitated using a ventilator, we hypothesized that breathing stimulants can prevent S-IRA and that fluoxetine prevents S-IRA by enhancing ventilation in these mice. Spontaneous respiratory function in anesthetized or awake DBA/1 mice was examined using noninvasive plethysmography before and after administering fluoxetine or breathing stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d] pyrimidine (PK-THPP). The effects of these drugs on S-IRA in DBA/1 mice were tested. As reported previously, systemic administration of fluoxetine reduced S-IRA in awake DBA/1 mice, but fluoxetine in anesthetized and awake DBA/1 mice did not increase basal ventilation or the ventilatory response to 7% CO2. Both doxapram and PK-THPP increased ventilation in room air and in air + 7% CO2 in anesthetized DBA/1mice. However, neither of the breathing stimulants reduced the incidence of S-IRA. Our studies confirm that fluoxetine reduces S-IRA in DBA/1micewithout enhancing basal ventilation in the absence of seizures. Although breathing stimulants increased ventilation in the absence of seizures, they were ineffective in reducing S-IRA, indicating that drug-induced increases in ventilation are insufficient to compensate for S-IRA in DBA/1 mice. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zeng, Chang; Cotten, Joseph F.; Forman, Stuart A.; Solt, Ken; Feng, Hua-Jun] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zeng, Chang] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zeng, Chang] Cent S Univ, Xiangya Hosp, Hlth Management Ctr, Changsha, Hunan, Peoples R China. [Long, Xiaoyan] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha, Hunan, Peoples R China. [Faingold, Carl L.] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA. RP Feng, HJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM feng.huajun@mgh.harvard.edu OI Solt, Ken/0000-0001-5328-2062 FU CURE (Citizens United for Research in Epilepsy) foundation [R03NS078591, R01HL117871]; Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine FX This work was supported by R03NS078591 and CURE (Citizens United for Research in Epilepsy) foundation to HJF and R01HL117871 to JC. We thank the support from the Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine. We thank Zuohao Li for the help with data analysis and figure preparation. NR 40 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2015 VL 45 BP 1 EP 7 DI 10.1016/j.yebeh.2015.02.013 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CH2BY UT WOS:000353830700001 PM 25771493 ER PT J AU Aviki, EM Rauh-Hain, JA Clark, RM Hall, TR Berkowitz, LR Boruta, DM Growdon, WB Schorge, JO Goodman, A AF Aviki, Emeline M. Rauh-Hain, J. Alejandro Clark, Rachel M. Hall, Tracilyn R. Berkowitz, Lori R. Boruta, David M. Growdon, Whitfield B. Schorge, John O. Goodman, Annekathryn TI Gynecologic Oncologist as surgical consultant: Intraoperative consultations during general gynecologic surgery as an important focus of gynecologic oncology training SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Intraoperative Consultation; Gynecologic Oncologist; Benign Surgery; Surgical Complications; Fellowship training ID HYSTERECTOMY; VOLUME; COMPLICATIONS; PERSPECTIVE; PATIENT; IMPACT AB Objective. The aim of this study is to explore the previously unexamined role of the Gynecologic Oncologist as an intraoperative consultant during general gynecologic surgery. Methods. Demographic and clinical data were collected on 98 major gynecologic surgeries that included both a general Gynecologist and a Gynecologic Oncologist between October 2010 and August 2014. Data were analyzed using XLSTAT-Prov20142.02. Results. Of 794 major gynecologic surgeries, 98 (12.3%) cases that involved an intraoperative consultation were identified. There were 36 (37%) planned consults and 62 (63%) unplanned consults. Significantly more planned consults were during laparoscopy (100% v 58%; p <0.01) and significantly more unplanned consults were during laparotomy (42% v 0%; p < 0.01). The majority of planned consults were for surgical training (86%) and the most common reasons for unplanned consults were adhesions (40%), bowel injury (19%), inability to identify ureter (19%), and cancer (11%). The most common interventions performed during unplanned consults were identification of anatomy (55%), lysis of adhesions (42%), and retroperitoneal dissection (27%). Average surgeon years in practice were significantly lower for unplanned consults (9 v 15; p <0.01). A total of 25 major adverse events occurred in 15 cases with the majority occurring in cases with unplanned consults (23% v 3%; p <0.01). After controlling for laparotomy, unplanned consultation was not significantly associated with major events (OR = 6.67, 95%Cl 0.69-64.39; p.= 0.10). Conclusions. Gynecologic Oncologists play a pivotal role in the support of generalist colleagues during pelvic surgery. In this series, Gynecologic Oncologists were consulted frequently for complex major benign surgeries. It is important to incorporate the skills required of an intraoperative consultant into Gynecologic Oncology fellowship training. (C) 2015 Elsevier Inc. All rights reserved. C1 [Aviki, Emeline M.; Rauh-Hain, J. Alejandro; Clark, Rachel M.; Hall, Tracilyn R.; Boruta, David M.; Growdon, Whitfield B.; Schorge, John O.; Goodman, Annekathryn] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Aviki, Emeline M.; Berkowitz, Lori R.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Aviki, Emeline M.; Rauh-Hain, J. Alejandro; Clark, Rachel M.; Hall, Tracilyn R.; Berkowitz, Lori R.; Boruta, David M.; Growdon, Whitfield B.; Schorge, John O.; Goodman, Annekathryn] Harvard Univ, Sch Med, Boston, MA USA. RP Aviki, EM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM eaviki@partners.org; agoodman@partners.org NR 22 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2015 VL 137 IS 1 BP 93 EP 97 DI 10.1016/j.ygyno.2015.01.536 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CG2BJ UT WOS:000353079600016 PM 25617772 ER PT J AU Yang, XQ Feng, Y Gao, Y Shen, J Choy, E Cote, G Harmon, D Zhang, Z Mankin, H Hornicek, FJ Duan, ZF AF Yang, Xiaoqian Feng, Yong Gao, Yan Shen, Jacson Choy, Edwin Cote, Gregory Harmon, David Zhang, Zhan Mankin, Henry Hornicek, Francis J. Duan, Zhenfeng TI NSC23925 prevents the emergence of multidrug resistance in ovarian cancer in vitro and in vivo SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Multidrug resistance; NSC23925; Ovarian cancer; Paclitaxel; Pgp ID X-RECEPTOR AGONIST; CELL LUNG-CANCER; DRUG-RESISTANCE; PACLITAXEL RESISTANCE; TUMOR XENOGRAFTS; MOLECULAR-MECHANISMS; BEXAROTENE LGD1069; TARGRETIN PREVENTS; VALSPODAR PSC-833; PHASE-II AB Objective. The development of multidrug resistance (MDR) remains the significant clinical challenge in ovarian cancer therapy; however, relatively little is known about how to prevent the emergence of MDR during chemotherapy treatment. NSC23925 previously has been shown to prevent the development of MDR in osteosarcoma cells in vitro. The purpose of this study was to evaluate the effects of NSC23925 on the prevention of MDR in ovarian cancer, especially in vivo. Methods. Human ovarian cancer cells were treated with paclitaxel alone or in combination with NSC23925 in vitro and in vivo. MDR ovarian cancer cells were established both in cultured cells and mouse models. The expression levels of Pgp and MDR1 were evaluated in various selected cell sublines by Western blot and real-time PCR. Pgp activity was also determined. Results. Paclitaxel treated cells eventually developed MDR with overexpression of Pgp and MDR1, and with high activity of Pgp, while paclitaxel-NSC23925 co-treated cells remained sensitive to chemotherapeutic agents in both in vitro and in vivo models. There was no observed increase in expression level and activity of Pgp in paclitaxel-NSC23925 co-treated cells. Additionally, there were no changes in the sensitivity to chemotherapeutic agents, nor expression of Pgp, in cells cultured with NSC23925. Conclusion. Our findings suggest that NSC23925 can prevent the emergence of MDR in ovarian cancer both in vitro and in vivo. The clinical use of NSC2395 at the onset of chemotherapy may prevent the development of MDR and: improve the clinical outcome of patients with ovarian cancer. (C) 2015 Elsevier Inc. All rights reserved. C1 [Yang, Xiaoqian; Feng, Yong; Gao, Yan; Shen, Jacson; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Yang, Xiaoqian; Feng, Yong; Gao, Yan; Shen, Jacson; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Xiaoqian; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Dept Gynaecol & Obstet, Zhengzhou 450052, Henan Province, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu OI Cote, Gregory/0000-0003-0181-886X FU Gattegno and Wechsler funds; Kenneth Stanton Fund; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH), UOI [CA 151452]; China Scholarship Council FX This work was supported in part by grants from the Gattegno and Wechsler funds. Support has also been provided by the Kenneth Stanton Fund. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA), and a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UOI, CA 151452. Dr. Yang is supported by Scholarship from China Scholarship Council. NR 40 TC 3 Z9 3 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2015 VL 137 IS 1 BP 134 EP 142 DI 10.1016/j.ygyno.2015.02.002 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CG2BJ UT WOS:000353079600023 PM 25677062 ER PT J AU Growdon, WB Groeneweg, J Byron, V DiGloria, C Borger, DR Tambouret, R Foster, R Chenna, A Sperinde, J Winslow, J Rueda, BR AF Growdon, Whitfield B. Groeneweg, Jolijn Byron, Virginia DiGloria, Celeste Borger, Darrell R. Tambouret, Rosemary Foster, Rosemary Chenna, Ahmed Sperinde, Jeff Winslow, John Rueda, Bo R. TI HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant SO GYNECOLOGIC ONCOLOGY LA English DT Article DE High grade endometrial carcinoma; HER2 over-expression; p95HER2; Trastuzumab resistance ID GYNECOLOGIC-ONCOLOGY-GROUP; METASTATIC BREAST-CANCER; UTERINE SEROUS CARCINOMA; PHASE-II TRIAL; EXTRACELLULAR DOMAIN; PROTEIN EXPRESSION; TRASTUZUMAB; AMPLIFICATION; LAPATINIB; OVEREXPRESSION AB Background. Subsets of high grade endometrial cancer (EnCa) over-express HER2 (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity utilizing trastuzumab, an approved platform for HER2 positive breast cancer (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may confer resistance. The objective of this investigation was to characterize the expression of the p95HER2 truncated variant in EnCa. Materials and methods. With institutional approval, 86 high grade EnCa tumors were identified with tumor specimens from surgeries performed between 2000 and 2011. Clinical data were collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry (IHC, HercepTest (R)), HERZ fluorescent in situ hybridization (FISH), along with total HER2 (H2T) and p95HER2 assessment with VeraTag (R) testing. Regression models were used to compare a cohort of 86 breast tumors selected for equivalent HER2 protein expression. Results. We identified 44 high grade endometrioid and 42 uterine serous carcinomas (USC). IHC identified high HER2 expression (2 + or 3+) in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC, 4 endometrioid). Both HER2 gene amplification and protein expression correlated with H2T values. High p95HER2 expression above 2.8 RF/mm(2) was observed in 53% (n = 54) with significant correlation with H2T levels. When matched to a cohort of 107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented with higher p95 levels (p < 0.001). Conclusions. These data demonstrate that compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly providing rationale for the trastuzumab resistance observed in EnCa. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Growdon, Whitfield B.; Groeneweg, Jolijn; Byron, Virginia; DiGloria, Celeste; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Growdon, Whitfield B.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Tambouret, Rosemary] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Borger, Darrell R.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Growdon, Whitfield B.; Borger, Darrell R.; Tambouret, Rosemary; Foster, Rosemary; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chenna, Ahmed; Sperinde, Jeff; Winslow, John] Monogram Biosci, San Francisco, CA 94080 USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, THR 933,55 Fruit St, Boston, MA 02114 USA. EM wgrowdon@partners.org FU institutional K12 Proton Share NCI Grant [C06 CA059267]; Advanced Medical Research Foundation; Vincent Department of Obstetrics and Gynecology Research Funds FX This research was funded by an institutional K12 Proton Share NCI Grant C06 CA059267 (WBG), and funding from the Advanced Medical Research Foundation (BRR) and Vincent Department of Obstetrics and Gynecology Research Funds (BRR). NR 41 TC 6 Z9 7 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2015 VL 137 IS 1 BP 160 EP 166 DI 10.1016/j.ygyno.2015.01.533 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CG2BJ UT WOS:000353079600026 PM 25602714 ER PT J AU Bellmunt, J AF Bellmunt, Joaquim TI Preface Bladder Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Bellmunt, Joaquim] Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, Boston, MA 02215 USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Bellmunt, J (reprint author), Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM Joaquim_bellmunt@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP XIII EP XIV DI 10.1016/j.hoc.2014.12.001 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000001 PM 25836942 ER PT J AU Orsola, A Palou, J Solsona, E AF Orsola, Anna Palou, Joan Solsona, Eduardo TI High-Risk Nonmuscle Invasive Bladder Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Nonmuscle invasive bladder cancer; High-risk bladder cancer; High-grade T1; HGT1; Carcinoma in situ; CIS; TUR; reTUR ID TRANSITIONAL-CELL CARCINOMA; BACILLUS-CALMETTE-GUERIN; RESTAGING TRANSURETHRAL RESECTION; MUSCULARIS MUCOSA INVASION; UROTHELIAL CARCINOMA; PROGNOSTIC-FACTORS; URINARY-BLADDER; PRACTICE RECOMMENDATIONS; MULTIVARIATE-ANALYSIS; IMMEDIATE CYSTECTOMY AB The risk of progression for high-grade Ti (HGT1) cancer has been recently established at 21% using updated information on large series and a metaanalysis. These outcomes are better than those classically expected supporting the rule of thirds for HGT1. The main limitation of this subgroup is that most studies are retrospective observational studies, which, compared with randomized controlled trials, are subject to various selection biases, carrying a higher risk of uncontrolled confounding factors, with potential preferential reporting of positive findings. C1 [Orsola, Anna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA 02115 USA. [Palou, Joan] Fundacio Puigvert, Dept Urol, Barcelona 08025, Spain. [Solsona, Eduardo] Inst Valenciano Oncol, Dept Urol, Valencia 46009, Spain. RP Orsola, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02115 USA. EM annaorsola@gmail.com NR 67 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP 227 EP + DI 10.1016/j.hoc.2014.10.009 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000007 PM 25836931 ER PT J AU Lucca, I Leow, JJ Shariat, SF Chang, SL AF Lucca, Ilaria Leow, Jeffrey J. Shariat, Shahrokh F. Chang, Steven L. TI Diagnosis and Management of Upper Tract Urothelial Carcinoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Upper tract urothelial carcinoma; Kidney neoplasms; Ureteral neoplasms; Urothelial carcinoma; Nephroureterectomy; Chemotherapy; Radiotherapy ID UPPER URINARY-TRACT; TRANSITIONAL-CELL-CARCINOMA; METASTATIC BLADDER-CANCER; ADJUVANT SYSTEMIC CHEMOTHERAPY; ARISTOLOCHIC ACID NEPHROPATHY; CISPLATIN-BASED CHEMOTHERAPY; RADICAL NEPHROURETERECTOMY; LAPAROSCOPIC NEPHROURETERECTOMY; ONCOLOGIC OUTCOMES; RENAL PELVIS AB While UTUC is relatively uncommon, it has an aggressive natural history and poor prognosis, which has not substantially improved over the past two decades. Nevertheless, continued research has led to the discovery of risk factors improving the prevention and early detection of UTUC. Although RNU remains the standard treatment for localized invasive UTUC, nephron-sparing surgery for selected patients has made considerable progress in the recent years. The stagnation in the prognosis of UTUC over the past two decades highlights the necessity for incorporating multimodal approaches including refinements in systemic chemotherapy and radiotherapy to attain better outcomes for patients with UTUC. C1 [Lucca, Ilaria; Shariat, Shahrokh F.] Med Univ Vienna, Vienna Gen Hosp, Ctr Comprehens Canc, Dept Urol, A-1090 Vienna, Austria. [Lucca, Ilaria] CHU Vaudois, Dept Urol, CH-1011 Lausanne, Switzerland. [Leow, Jeffrey J.; Chang, Steven L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Inst, Dept Urol,Bladder Canc Ctr, Boston, MA 02215 USA. [Leow, Jeffrey J.; Chang, Steven L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol,Ctr Surg & Publ Hlth, Boston, MA 02215 USA. [Shariat, Shahrokh F.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75235 USA. [Shariat, Shahrokh F.] Cornell Univ, New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. RP Lucca, I (reprint author), Med Univ Vienna, Vienna Gen Hosp, Ctr Comprehens Canc, Dept Urol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM luccaila@gmail.com FU CHUV-University Hospital FX Development fund of the CHUV-University Hospital (I. Lucca); Nil (J.J. Leow, S.F. Shariat, and S.L. Chang). NR 141 TC 6 Z9 7 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP 271 EP + DI 10.1016/j.hoc.2014.10.003 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000010 PM 25836934 ER PT J AU Jani, AB Efstathiou, JA Shipley, WU AF Jani, Ashesh B. Efstathiou, Jason A. Shipley, William U. TI Bladder Preservation Strategies SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Bladder cancer; Cystectomy; Chemotherapy; Radiotherapy; Organ preservation ID THERAPY-ONCOLOGY-GROUP; RADICAL CYSTECTOMY; RADIATION-THERAPY; ADJUVANT CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; TRANSURETHRAL SURGERY; UROTHELIAL CARCINOMA; URINARY-BLADDER; PHASE-II; CANCER AB Although cystectomy remains the standard for treatment of muscle-invasive bladder cancer in the United States, there exist potentially curative alternatives for a selected subset of these patients in organ preservation using concurrent chemotherapy with radiation following an aggressive transurethral resection of the tumor. Chemotherapy and radiotherapy in combination, with salvage cystectomy for invasive recurrence, have produced 10-year disease-specific survival rates of 60% to 65% with overall survival similar to that of cystectomy in selected patients. Fine-tuning of the chemoradiotherapy sequencing, timing, and fractionation has been reported in both singlecenter and cooperative group publications from North America and Europe. C1 [Jani, Ashesh B.] Emory Univ, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Efstathiou, Jason A.; Shipley, William U.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jani, AB (reprint author), Emory Univ, Dept Radiat Oncol, 1365 Clifton Rd,Northeast,Suite A1300, Atlanta, GA 30322 USA. EM abjani@emory.edu NR 44 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP 289 EP + DI 10.1016/j.hoc.2014.10.004 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000011 PM 25836935 ER PT J AU Leow, JJ Fay, AP Mullane, SA Bellmunt, J AF Leow, Jeffrey J. Fay, Andre P. Mullane, Stephanie A. Bellmunt, Joaquim TI Perioperative Therapy for Muscle Invasive Bladder Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Urinary bladder neoplasms; Neoadjuvant therapy; Adjuvant therapy; Chemotherapy; Radiotherapy; Radical cystectomy; Chemotherapy ID TRANSITIONAL-CELL-CARCINOMA; CHEMOTHERAPY FOLLOWING CYSTECTOMY; EAU INTERNATIONAL CONSULTATION; ADVANCED UROTHELIAL CARCINOMA; INDIVIDUAL PATIENT DATA; RANDOMIZED PHASE-III; RADICAL CYSTECTOMY; ADJUVANT CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; METHOTREXATE CHEMOTHERAPY AB Muscle invasive bladder cancer (MIBC) is an aggressive disease associated with poor survival rates. High rates of relapse, despite radical cystectomy, suggest that administration of systemic therapy in the perioperative period may improve clinical outcomes. Neoadjuvant treatment with cisplatin-based combination regimens is an established standard of care and has improved long-term survival in MIBC. As the use of neoadjuvant chemotherapy steadily increases, clinicians still need to decide about administering adjuvant chemotherapy to patients with high-risk disease. This review examines in detail the latest evidence available for both neoadjuvant and adjuvant chemotherapy, and highlights pertinent studies. C1 [Leow, Jeffrey J.; Fay, Andre P.; Mullane, Stephanie A.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Inst, Bladder Canc Ctr, Boston, MA 02115 USA. [Leow, Jeffrey J.] Tan Tock Seng Hosp, Dept Urol, Singapore, Singapore. [Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain. RP Leow, JJ (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Inst, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02115 USA. EM jeffrey.leow@mail.harvard.edu NR 89 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP 301 EP + DI 10.1016/j.hoc.2014.11.002 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000012 PM 25836936 ER PT J AU Narayanan, S Harshman, LC Srinivas, S AF Narayanan, Sujata Harshman, Lauren C. Srinivas, Sandy TI Second-Line Therapies in Metastatic Urothelial Carcinoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Refractory; Therapies in urothelial cancer; Chemotherapy; Targeted; Immunotherapy ID TRANSITIONAL-CELL CARCINOMA; PHASE-II TRIAL; GROWTH-FACTOR-RECEPTOR; COOPERATIVE-ONCOLOGY-GROUP; PLATINUM-CONTAINING REGIMEN; GEMCITABINE PLUS CISPLATIN; INVASIVE BLADDER-CANCER; LONG-TERM-SURVIVAL; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL AB Patients with relapsed or refractory urothelial carcinoma (UC) face a poor prognosis and a dearth of available treatment options that improve their survival. End-organ function and performance status play a vital role in the choice of second-line therapies. Evidence supporting the use of cytotoxic chemotherapy, as single agents or in combination, arises from small phase 2 studies with modest responses. With the evolution of genomic testing in UC, several pathways amenable to available targeted therapies have emerged. Encouraging patient participation in clinical trials is critical to improve patient outcomes and to advance the current modest treatment armamentarium. C1 [Narayanan, Sujata; Srinivas, Sandy] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Harshman, Lauren C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02215 USA. RP Srinivas, S (reprint author), Stanford Univ, Sch Med, Dept Med, Blake Wilbur Dr, Stanford, CA 94305 USA. EM sandysri@stanford.edu NR 99 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP 341 EP + DI 10.1016/j.hoc.2014.10.007 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000015 PM 25836939 ER PT J AU Sonpavde, G Jones, BS Bellmunt, J Choueiri, TK Sternberg, CN AF Sonpavde, Guru Jones, Benjamin S. Bellmunt, Joaquim Choueiri, Toni K. Sternberg, Cora N. TI Future Directions and Targeted Therapies in Bladder Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Urothelial carcinoma; Biologic agents; Therapeutic targets; Systemic therapy ID METASTATIC UROTHELIAL CANCER; CISPLATIN-BASED CHEMOTHERAPY; PHASE-II TRIAL; TRANSITIONAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; PROGRESSION-FREE SURVIVAL; 2ND-LINE TREATMENT; ONCOLOGY-GROUP; DOUBLE-BLIND; IN-VIVO AB There are substantial unmet needs for patients with metastatic urothelial carcinoma (UC). First-line cisplatin-based chemotherapy regimens yield a median survival of 12 to 15 months and long-term survival in 5% to 15%. Salvage systemic therapy yields a median survival of 6 to 8 months. Hence, the discovery of novel therapeutic targets is of paramount importance. Recent molecular analyses have provided insights regarding molecular tumor tissue alterations on multiple platforms. A multidisciplinary effort using innovative clinical trial designs and exploiting preclinical signals of robust activity guided by predictive biomarkers may provide much needed clinical advances in therapy for advanced UC. C1 [Sonpavde, Guru; Jones, Benjamin S.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Bellmunt, Joaquim; Choueiri, Toni K.] Dana Farber Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Bladder Canc Inst, Boston, MA 02215 USA. [Sternberg, Cora N.] San Camillo Forlanini Hosp, Dept Med Oncol, I-00152 Rome, Italy. RP Sternberg, CN (reprint author), San Camillo Forlanini Hosp, Dept Med Oncol, 1st Floor,Circonvallaz Gianicolense 87, I-00152 Rome, Italy. EM cstern@mclink.it FU Onyx; Sanofi-Aventis; Oncogenix; AstraZeneca; Amgen; Bayer; Novartis; GSK FX Research support from Onyx, Sanofi-Aventis; advisory board of GSK, Bayer, Merck, Genentech, Sanofi-Aventis (G. Sonpavde). None (B.S. Jones). Advisory board of Pierre Fabre, Sanofi-Aventis, GSK, Genentech, and Merck (J. Bellmunt). Institutional research support from Oncogenix, AstraZeneca, Amgen (T.K. Choueiri). Institutional research support from Oncogenix; GSK, Bayer, Novartis; honoraria, Bayer, Novartis (C.N. Sternberg). NR 98 TC 10 Z9 10 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2015 VL 29 IS 2 BP 361 EP + DI 10.1016/j.hoc.2014.10.008 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA CG6RL UT WOS:000353430000016 PM 25836940 ER PT J AU Marshall, MR Young, BA Fox, SJ Cleland, CJ Walker, RJ Maskane, I Herold, AM AF Marshall, Mark R. Young, Bessie A. Fox, Sally J. Cleland, Calli J. Walker, Robert J. Maskane, Ikuto Herold, Aaron M. TI The home hemodialysis hub: Physical infrastructure and integrated governance structure SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Infrastructure; governance; home hemodialysis; dialysis ID EXPERIENCE; DIALYSIS; PROGRAM; CHRISTCHURCH; BARRIERS AB An effective home hemodialysis program critically depends on adequate hub facilities and support functions and on transparent and accountable organizational processes. The likelihood of optimal service delivery and patient care will be enhanced by fit-for-purpose facilities and implementation of a well-considered governance structure. In this article, we describe the required accommodation and infrastructure for a home hemodialysis program and a generic organizational structure that will support both patient-facing clinical activities and business processes. C1 [Marshall, Mark R.] Univ Auckland, Fac Med & Hlth Sci, Auckland 1142, New Zealand. [Marshall, Mark R.; Fox, Sally J.; Cleland, Calli J.] Counties Manukau Dist Hlth Board, Dept Renal Med, Auckland, New Zealand. [Young, Bessie A.] Univ Washington, Div Nephrol, Kidney Res Inst, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Walker, Robert J.] Univ Otago, Dunedin Sch Med, Dept Med, Dunedin, New Zealand. [Maskane, Ikuto] Yabuki Hosp, Kidney & Dialysis Ctr, Yamagata, Japan. [Herold, Aaron M.] Northwest Kidney Ctr, Operat Support, Seattle, WA USA. RP Marshall, MR (reprint author), Univ Auckland, Fac Med & Hlth Sci, Private Bag 92019, Auckland 1142, New Zealand. EM mrmarsh@woosh.co.nz FU Baxter; Fresenius Medical Care, Asia-Pacific; Auckland Medical Research Foundation; Gambro Pty Ltd (New Zealand); Fresenius Medical Care Australia Pty Ltd; Fresenius Medical Care Asia-Pacific Pty Ltd; Health Research Council of New Zealand; Kidney Health New Zealand; Lottery Health Research Foundation (New Zealand); Maurine and Phyllis Paykel Trust; New Zealand Ministry of Health; Royal Australasian College of Physicians Jacquot Foundation; Amgen; Ineos Healthcare Limited; Fresenius Medical Care FX MM is currently employed as the Director of Medical Affairs, Asia-Pacific, by Baxter Healthcare Corporation and previously served as a paid consultant to Baxter and Fresenius Medical Care, Asia-Pacific. He has received grant support from the Auckland Medical Research Foundation, Gambro Pty Ltd (New Zealand), Fresenius Medical Care Australia Pty Ltd, Fresenius Medical Care Asia-Pacific Pty Ltd, Health Research Council of New Zealand, Kidney Health New Zealand (formerly the National Kidney Foundation, New Zealand), Lottery Health Research Foundation (New Zealand), Maurine and Phyllis Paykel Trust, New Zealand Ministry of Health, and The Royal Australasian College of Physicians Jacquot Foundation. He has been an investigator for clinical trials sponsored by Amgen, Ineos Healthcare Limited, and Fresenius Medical Care. NR 25 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 EI 1542-4758 J9 HEMODIAL INT JI Hemodial. Int. PD APR PY 2015 VL 19 SU 1 SI SI BP S8 EP S22 DI 10.1111/hdi.12273 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA CH3WC UT WOS:000353960400003 PM 25925827 ER PT J AU Neilan, TG Farhad, H Mayrhofer, T Shah, RV Dodson, JA Abbasi, SA Danik, SB Verdini, DJ Tokuda, M Tedrow, UB Jerosch-Herold, M Hoffmann, U Ghoshhajra, BB Stevenson, WG Kwong, RY AF Neilan, Tomas G. Farhad, Hoshang Mayrhofer, Thomas Shah, Ravi V. Dodson, John A. Abbasi, Siddique A. Danik, Stephan B. Verdini, Daniel J. Tokuda, Michifumi Tedrow, Usha B. Jerosch-Herold, Michael Hoffmann, Udo Ghoshhajra, Brian B. Stevenson, William G. Kwong, Raymond Y. TI Late Gadolinium Enhancement Among Survivors of Sudden Cardiac Arrest SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; implantable cardioverter-defibrillator; late gadolinium enhancement ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CARDIOVASCULAR MAGNETIC-RESONANCE; ANTIARRHYTHMIC-DRUG THERAPY; CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; NONISCHEMIC CARDIOMYOPATHY; VENTRICULAR-ARRHYTHMIAS; PRIMARY PREVENTION; TACHYCARDIA; PROGNOSIS AB OBJECTIVES The aim of this study was to describe the role of contrast-enhanced cardiac magnetic resonance (CMR) in the workup of patients with aborted sudden cardiac arrest (SCA) and in the prediction of long-term outcomes. BACKGROUND Myocardial fibrosis is a key substrate for SCA, and late gadolinium enhancement (LGE) on a CMR study is a robust technique for imaging of myocardial fibrosis. METHODS We performed a retrospective review of all survivors of SCA who were referred for CMR studies and performed follow-up for the subsequent occurrence of an adverse event (death and appropriate defibrillator therapy). RESULTS After a workup that included a clinical history, electrocardiogram, echocardiography, and coronary angiogram, 137 patients underwent CMR for workup of aborted SCA (66% male; mean age 56 +/- 11 years; left ventricular ejection fraction 43 +/- 12%). The presenting arrhythmias were ventricular fibrillation (n = 105 [77%]) and ventricular tachycardia (n = 32 [23%]). Overall, LGE was found in 98 patients (71%), with an average extent of 9.9 +/- 5% of the left ventricular myocardium. CMR imaging provided a diagnosis or an arrhythmic substrate in 104 patients (76%), including the presence of an infarct-pattern LGE in 60 patients (44%), noninfarct LGE in 21(15%), active myocarditis in 14 (10%), hypertrophic cardiomyopathy in 3 (2%), sarcoidosis in 3, and arrhythmogenic cardiomyopathy in 3. In a median follow-up of 29 months (range 18 to 43 months), there were 63 events. In a multivariable analysis, the strongest predictors of recurrent events were the presence of LGE (adjusted hazard ratio: 6.7; 95% CI: 2.38 to 18.85; p < 0.001) and the extent of LGE (hazard ratio: 1.15; 95% CI: 1.11 to 1.19; p < 0.001). CONCLUSIONS Among patients with SCA, CMR with contrast identified LGE in 71% and provided a potential arrhythmic substrate in 76%. In follow-up, both the presence and extent of LGE identified a group at markedly increased risk of future adverse events. (C) 2015 by the American College of Cardiology Foundation. C1 [Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Neilan, Tomas G.; Mayrhofer, Thomas; Verdini, Daniel J.; Hoffmann, Udo; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Farhad, Hoshang; Shah, Ravi V.; Dodson, John A.; Abbasi, Siddique A.; Tokuda, Michifumi; Tedrow, Usha B.; Stevenson, William G.; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Boston, MA 02115 USA. [Danik, Stephan B.] Mt Sinai St Lukes Roosevelt Hosp, Dept Med, Div Cardiol, New York, NY USA. [Jerosch-Herold, Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Kwong, RY (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Cardiac Magnet Resonance Imaging, 75 Francis St, Boston, MA 02115 USA. EM rykwong@partners.org OI Abbasi, Siddique/0000-0002-9601-7565 FU National Institutes of Health research grants [R01HL090634-01A1, R01HL091157]; AstraZeneca Scholarship of the Swiss Society of Hypertension; St. Jude Medical; Biosense Webster; [12FTF12060588] FX This work was supported by an American Heart Association Fellow to Faculty grant to Dr. Neilan (12FTF12060588) and National Institutes of Health research grants to Dr. Jerosch-Herold (R01HL090634-01A1) and Dr. Kwong (R01HL091157). Dr. Farhad is supported in part by the AstraZeneca Scholarship of the Swiss Society of Hypertension. Dr. Tedrow has received honorarium from Medtronic and St. Jude Medical; and research funding from St. Jude Medical and Biosense Webster. Dr. Ghoshhajra has received honoraria from Siemens Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 34 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2015 VL 8 IS 4 BP 414 EP 423 DI 10.1016/j.jcmg.2014.11.017 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG6TI UT WOS:000353434900005 PM 25797123 ER PT J AU Lehrer-Graiwer, J Singh, P Abdelbaky, A Vucic, E Korsgren, M Baruch, A Fredrickson, J van Bruggen, N Tang, MT Frendeus, B Rudd, JHF Hsieh, F Ballantyne, CM Ghoshhajra, B Rosenson, RS Koren, M Roth, EM Duprez, DA Fayad, ZA Tawakol, AA AF Lehrer-Graiwer, Joshua Singh, Parmanand Abdelbaky, Amr Vucic, Esad Korsgren, Magnus Baruch, Amos Fredrickson, Jill van Bruggen, Nick Tang, Meina T. Frendeus, Bjorn Rudd, James H. F. Hsieh, Frank Ballantyne, Christie M. Ghoshhajra, Brian Rosenson, Robert S. Koren, Michael Roth, Eli M. Duprez, Daniel A. Fayad, Zahi A. Tawakol, Ahmed A. TI FDG-PET Imaging for Oxidized LDL in Stable Atherosclerotic Disease: A Phase II Study of Safety, Tolerability, and Anti-Inflammatory Activity SO JACC-CARDIOVASCULAR IMAGING LA English DT Letter C1 [Lehrer-Graiwer, Joshua; Singh, Parmanand; Abdelbaky, Amr; Vucic, Esad; Korsgren, Magnus; Baruch, Amos; Fredrickson, Jill; van Bruggen, Nick; Tang, Meina T.; Frendeus, Bjorn; Rudd, James H. F.; Hsieh, Frank; Ballantyne, Christie M.; Ghoshhajra, Brian; Rosenson, Robert S.; Koren, Michael; Roth, Eli M.; Duprez, Daniel A.; Fayad, Zahi A.; Tawakol, Ahmed A.] Massachusetts Gen Hosp, MR PET CT Program, Boston, MA 02114 USA. RP Lehrer-Graiwer, J (reprint author), Massachusetts Gen Hosp, MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org OI Rudd, James/0000-0003-2243-3117 FU NHLBI NIH HHS [5T32 HL076136] NR 3 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD APR PY 2015 VL 8 IS 4 BP 493 EP 494 DI 10.1016/j.jcmg.2015.06.021 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG6TI UT WOS:000353434900015 PM 25457756 ER PT J AU Rosenfield, RL DiMeglio, LA Mauras, N Ross, J Shaw, ND Greeley, SAW Haymond, M Rubin, K Rhodes, ET AF Rosenfield, Robert L. DiMeglio, Linda A. Mauras, Nelly Ross, Judith Shaw, Natalie D. Greeley, Siri A. W. Haymond, Morey Rubin, Karen Rhodes, Erinn T. TI Commentary: Launch of a Quality Improvement Network for Evidence-Based Management of Uncommon Pediatric Endocrine Disorders: Turner Syndrome as a Prototype SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID HORMONE REPLACEMENT THERAPY; VENOUS THROMBOEMBOLISM; FINAL HEIGHT; GIRLS; RISK; ESTRADIOL; CONTRACEPTION; ESTROGEN; STROKE AB Background: Traditional, hypothesis-oriented research approaches have thus far failed to generate sufficient evidence to achieve consensus about the management of children with many endocrine disorders, partly because of the rarity of these disorders and because of regulatory burdens unique to research in children. Objective: The Pediatric Endocrine Society is launching a quality improvement network in spring 2015 for the management of pediatric endocrine disorders that are relatively uncommon in any single practice and/or for which there is no consensus on management. Design: The first of the quality improvement programs to be implemented seeks to improve the care of 11- to 17-year-old girls with Turner syndrome who require initiation of estrogen replacement therapy by providing a standardized clinical assessment and management plan (SCAMP) for transdermal estradiol treatment to induce pubertal development. The SCAMP algorithm represents a starting point within current best practice that is meant to undergo refinement through an iterative process of analysis of deidentified data collected in the course of clinical care by a network of pediatric endocrinologists. Conclusion: It is anticipated that this program will not only improve care, but will also result in actionable data that will generate new research hypotheses and changes in management of pediatric endocrine disorders. C1 [Rosenfield, Robert L.; Greeley, Siri A. W.] Univ Chicago, Pritzker Sch Med, Sect Adult & Pediat Endocrinol Metab & Diabet, Chicago, IL 60637 USA. [DiMeglio, Linda A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Mauras, Nelly] Nemours Childrens Clin, Div Endocrinol Diabet & Metab, Jacksonville, FL 32207 USA. [Ross, Judith] Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. [Ross, Judith] Nemours duPont Hosp Children, Wilmington, DE 19803 USA. [Shaw, Natalie D.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Shaw, Natalie D.; Rhodes, Erinn T.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Haymond, Morey] Baylor Coll Med, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. [Rubin, Karen] Connecticut Childrens Med Ctr, Hartford, CT 06106 USA. [Rubin, Karen] Univ Connecticut, Sch Med, Farmington, CT 06032 USA. RP Rosenfield, RL (reprint author), Univ Chicago, Med Ctr, Sect Adult & Pediat Endocrinol Metab & Diabet, 5841 South Maryland Ave,MC 5053, Chicago, IL 60637 USA. EM robros@peds.bsd.uchicago.edu OI Shaw, Natalie/0000-0002-0847-9170 FU NIDDK NIH HHS [K23 DK094866, P30 DK020595] NR 20 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP 1234 EP 1236 DI 10.1210/jc.2014-3845 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500027 PM 25844763 ER PT J AU Yu, EW Bouxsein, ML Putman, MS Monis, EL Roy, AE Pratt, JSA Butsch, WS Finkelstein, JS AF Yu, Elaine W. Bouxsein, Mary L. Putman, Melissa S. Monis, Elizabeth L. Roy, Adam E. Pratt, Janey S. A. Butsch, W. Scott Finkelstein, Joel S. TI Two-Year Changes in Bone Density After Roux-en-Y Gastric Bypass Surgery SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BARIATRIC SURGERY; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; MORBID-OBESITY; DISTAL RADIUS; HR-PQCT; WEIGHT; MASS; MICROARCHITECTURE; TURNOVER AB Context: Bariatric surgery is increasingly popular but may lead to metabolic bone disease. Objective: The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass. Design and Setting: This was a prospective cohort study conducted at an academic medical center. Participants: The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls. Outcomes: We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis. Results: Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months ( - 37 +/- 3 vs - 5 +/- 3 kg [ mean +/- SEM]; P < 001). At 24 months, BMD was 5-7% lower at the spineand 6-10% lower at the hipin subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry ( P < 001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25( OH)-vitamin D, and PTH were maintained within the normal range in both groups. Conclusions: Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern. C1 [Yu, Elaine W.; Bouxsein, Mary L.; Putman, Melissa S.; Monis, Elizabeth L.; Roy, Adam E.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Pratt, Janey S. A.; Butsch, W. Scott] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. RP Yu, EW (reprint author), MGHEndocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM ewyu@partners.org FU National Institutes of Health (NIH) [K12 HD51959, K23 DK093713, P30 DK0462001, UL1 RR025758, S10 RR023405] FX This work was supported by National Institutes of Health (NIH) Grants K12 HD51959, K23 DK093713, and P30 DK046200. The Clinical Research Center was supported by NIH Grant 1 UL1 RR025758, and the HR-pQCT Core Facility was supported by NIH Grant S10 RR023405. NR 32 TC 15 Z9 16 U1 2 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP 1452 EP 1459 DI 10.1210/jc.2014-4341 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500053 PM 25646793 ER PT J AU Aroda, VR Christophi, CA Edelstein, SL Zhang, P Herman, WH Barrett-Connor, E Delahanty, LM Montez, MG Ackermann, RT Zhuo, X Knowler, WC Ratner, RE AF Aroda, V. R. Christophi, C. A. Edelstein, S. L. Zhang, P. Herman, W. H. Barrett-Connor, E. Delahanty, L. M. Montez, M. G. Ackermann, R. T. Zhuo, X. Knowler, W. C. Ratner, R. E. CA Diabet Prevention Program Res Grp TI The Effect of Lifestyle Intervention and Metformin on Preventing or Delaying Diabetes Among Women With and Without Gestational Diabetes: The Diabetes Prevention Program Outcomes Study 10-Year Follow-Up SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ORAL GLUCOSE-TOLERANCE; CLINICAL-TRIAL; MELLITUS; MODELS AB Context: Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM. Objective: The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study. Design: This was a randomized controlled clinical trial with an observational follow-up. Setting: The study was conducted at 27 clinical centers. Participants: Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry. Interventions: Interventions included placebo, ILS, or metformin. Outcomes Measure: Outcomes measure was diabetes mellitus. Results: Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. Conclusions: Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes. C1 [Aroda, V. R.; Ratner, R. E.] MedStar Hlth Res Inst, Hyattsville, MD 20782 USA. [Christophi, C. A.; Edelstein, S. L.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Zhang, P.; Zhuo, X.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Herman, W. H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Barrett-Connor, E.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Delahanty, L. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delahanty, L. M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Montez, M. G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ackermann, R. T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Knowler, W. C.] NIDDK, Phoenix, AZ 85014 USA. RP Aroda, VR (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 FU National Institutes of Health, NIDDK [U01-DK048489] FX This work was supported by the National Institutes of Health, NIDDK, under U01-DK048489. NR 17 TC 30 Z9 33 U1 2 U2 10 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP 1646 EP 1653 DI 10.1210/jc.2014-3761 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500076 PM 25706240 ER PT J AU Irving, BA Lanza, IR Henderson, GC Rao, RR Spiegelman, BM Nair, KS AF Irving, Brian A. Lanza, Ian R. Henderson, Gregory C. Rao, Rajesh R. Spiegelman, Bruce M. Nair, K. Sreekumaran TI Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROTEIN-SYNTHESIS; ENDURANCE EXERCISE; ENZYME-ACTIVITY; OLDER-ADULTS; IN-VITRO; RESISTANCE; INSULIN; METABOLISM; IMPACT; INDIVIDUALS AB Context: Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity. Objective: The primary objective was to determine whether 8 weeks of combined training (CT) has a more robust effect than endurance training (ET) or resistance training (RT) on mitochondrial physiology in healthy young (18-30 years) and older (>= 65 years) adults. Intervention: Thirty-four young and 31 older adults were randomly assigned to 8 weeks of ET, RT, and control/CT. Control subjects completed 8 weeks of no exercise (control) followed by 8 weeks of CT. Body composition, skeletal muscle strength, and peak oxygen uptake were measured before and after the intervention. Vastus lateralis muscle biopsy samples were obtained before and 48 hours after the intervention. Mitochondrial physiology was evaluated by high-resolution respirometry and expression of mitochondrial proteins and transcription factors by quantitative PCR and immunoblotting. Results: ET and CT significantly increased oxidative capacity and expression of mitochondrial proteins and transcription factors. All training modalities improved body composition, cardiorespiratory fitness, and skeletal muscle strength. CT induced the most robust improvements in mitochondria-related outcomes and physical characteristics despite lower training volumes for the ET and RT components. Importantly, most of the adaptations to training occurred independent of age. Conclusion: Collectively, these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity although CT induced the most robust improvements in the outcomes measured. In conclusion, CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age. C1 [Irving, Brian A.; Lanza, Ian R.; Henderson, Gregory C.; Nair, K. Sreekumaran] Mayo Clin, Coll Med, Endocrine Res Unit, Div Endocrinol, Rochester, MN 55905 USA. [Rao, Rajesh R.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Rao, Rajesh R.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Nair, KS (reprint author), Mayo Clin, Div Endocrinol, 200 First St SW,Joseph 5-193, Rochester, MN 55905 USA. EM bairving@geisigner.edu; nair@mayo.edu RI Irving, Brian/B-9683-2016 OI Irving, Brian/0000-0002-4131-9523 FU National Institutes of Health [R01AG09531, R01DK41973, KL2RR024151, UL1 TR000135]; Mayo Foundation; National Center for Advancing Translational Sciences, a component of the National Institutes of Health (Clinical and Translational Science Awards Grant) [UL1-TR000135] FX This work was supported by the National Institutes of Health (grants R01AG09531, R01DK41973 [to K.S.N.], KL2RR024151 [to B.A.I.], and UL1 TR000135), the Mayo Foundation, the Murdock-Dole Professorship (to K.S.N.), and the National Center for Advancing Translational Sciences, a component of the National Institutes of Health (Clinical and Translational Science Awards Grant UL1-TR000135). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. NR 39 TC 14 Z9 14 U1 1 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP 1654 EP 1663 DI 10.1210/jc.2014-3081 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500077 PM 25599385 ER PT J AU Rao, MN Neylan, TC Grunfeld, C Mulligan, K Schambelan, M Schwarz, JM AF Rao, Madhu N. Neylan, Thomas C. Grunfeld, Carl Mulligan, Kathleen Schambelan, Morris Schwarz, Jean-Marc TI Subchronic Sleep Restriction Causes Tissue-Specific Insulin Resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FATTY-ACID-METABOLISM; GLUCOSE-PRODUCTION; CARBOHYDRATE-METABOLISM; INFECTED PATIENTS; HUMANS; LIPOLYSIS; STIMULATION; SENSITIVITY; SECRETION; CORTISOL AB Context: Short sleep duration is associated with an increased risk of type 2 diabetes. Subchronic sleep restriction (SR) causes insulin resistance, but the mechanisms and roles of specific tissues are unclear. Objective: The purpose of this article was to determine whether subchronic SR altered (1) hepatic insulin sensitivity, (2) peripheral insulin sensitivity, and (3) substrate utilization. Design: This was a randomized crossover study in which 14 subjects underwent 2 admissions separated by a washout period. Each admission had 2 acclimatization nights followed by 5 nights of either SR (4 hours time in bed) or normal sleep (8 hours time in bed). Main Outcome Measure/Methods: Insulin sensitivity (measured by hyperinsulinemic-euglycemic clamp) and hepatic insulin sensitivity (measured by stable isotope techniques) were measured. In addition, we assayed stress hormone (24-hour urine free cortisol, metanephrine, and normetanephrine), nonesterified fatty acid (NEFA), and beta-hydroxybutyrate (beta-OH butyrate) levels. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured by indirect calorimetry. Results: Compared to normal sleep, whole-body insulin sensitivity decreased by 25% (P = .008) with SR and peripheral insulin sensitivity decreased by 29% (P = .003). Whereas hepatic insulin sensitivity (endogenous glucose production) did not change significantly, percent gluconeogenesis increased (P = .03). Stress hormones increased modestly (cortisol by 21%, P = .04; metanephrine by 8%, P = .014; normetanephrine by 18%, P = .002). Fasting NEFA and beta-OH butyrate levels increased substantially (62% and 55%, respectively). REE did not change (P = 0.98), but RQ decreased (0.81 +/- .02 vs 0.75 +/- 0.02, P = .045). Conclusion: Subchronic SR causes unique metabolic disturbances characterized by peripheral, but not hepatic, insulin resistance; this was associated with a robust increase in fasting NEFA levels (indicative of increased lipolysis), decreased RQ, and increased beta-OH butyrate levels (indicative of whole-body and hepatic fat oxidation, respectively). We postulate that elevated NEFA levels are partially responsible for the decrease in peripheral sensitivity and modulation of hepatic metabolism (ie, increase in gluconeogenesis without increase in endogenous glucose production). Elevated cortisol and metanephrine levels may contribute to insulin resistance by increasing lipolysis and NEFA levels. C1 [Rao, Madhu N.; Neylan, Thomas C.; Grunfeld, Carl] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Rao, Madhu N.; Grunfeld, Carl; Mulligan, Kathleen; Schambelan, Morris; Schwarz, Jean-Marc] Univ Calif San Francisco, Dept Med, Div Endocrinol & Metab, San Francisco, CA 94143 USA. [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Schwarz, Jean-Marc] Touro Univ, Vallejo, CA 94592 USA. RP Rao, MN (reprint author), San Francisco VA Med Ctr, 111F,4150 Clement St, San Francisco, CA 94121 USA. EM madhu.rao@ucsf.edu FU National Institutes of Health (National Heart, Lung, and Blood Institute Grant) [K23HL096832]; National Institutes of Health (National Center for Research Resources Grant) [UL 1 TR000004] FX This work was supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute Grant K23HL096832, National Center for Research Resources Grant UL 1 TR000004) and with resources and the use of the facilities of the San Francisco Veterans' Affairs Medical Center NR 38 TC 13 Z9 13 U1 1 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP 1664 EP 1671 DI 10.1210/jc.2014-3911 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500078 PM 25658017 ER PT J AU Brehin, AC Colson, C Maupetit-Mehouas, S Grybek, V Richard, N Linglart, A Kottler, ML Juppner, H AF Brehin, Anne-Claire Colson, Cindy Maupetit-Mehouas, Stephanie Grybek, Virginie Richard, Nicolas Linglart, Agnes Kottler, Marie-Laure Jueppner, Harald TI Loss of Methylation at GNAS Exon A/B Is Associated With Increased Intrauterine Growth SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PSEUDOHYPOPARATHYROIDISM TYPE-IB; XL-ALPHA-S; ALBRIGHTS HEREDITARY OSTEODYSTROPHY; PARATHYROID-HORMONE RESISTANCE; IMPRINTING CONTROL ELEMENT; PHYSIOLOGICAL FUNCTIONS; UNIPARENTAL DISOMY; EPIGENETIC DEFECTS; FETAL-GROWTH; GENE AB Context: GNAS is one of few genetic loci that undergo allelic-specific methylation resulting in the parent-specific expression of at least four different transcripts. Due to monoallelic expression, heterozygous GNAS mutations affecting either paternally or maternally derived transcripts cause different forms of pseudohypoparathyroidism (PHP), including autosomal-dominant PHP type Ib (AD-PHP1B) associated with loss of methylation (LOM) at exon A/B alone or sporadic PHP1B (sporPHP1B) associated with broad GNAS methylation changes. Similar to effects other imprinted genes have on early development, we recently observed severe intrauterine growth retardation in newborns, later diagnosed with pseudopseudohypoparathyroidism (PPHP) because of paternal GNAS loss-of-function mutations. Objectives: This study aimed to determine whether GNAS methylation abnormalities affect intrauterine growth. Patients and Methods: Birth parameters were collected of patients who later developed sporPHP1B or AD-PHP1B, and of their healthy siblings. Comparisons were made to newborns affected by PPHP or PHP1A. Results: As newborns, AD-PHP1B patients were bigger than their healthy siblings and well above the reference average; increased sizes were particularly evident if the mothers were unaffected carriers of STX16 deletions. SporPHP1B newborns were slightly above average for weight and length, but their overgrowth was less pronounced than that of AD-PHP1B newborns from unaffected mothers. Conclusion: LOM at GNAS exon A/B due to maternal STX16 deletions and the resulting biallelic A/B expression are associated with enhanced fetal growth. These findings are distinctly different from those of PPHP patients with paternal GNAS exons 2-13 mutations, whose birth parameters are almost 4.5 z-scores below those of AD-PHP1B patients born to healthy mothers. C1 [Brehin, Anne-Claire; Colson, Cindy; Richard, Nicolas; Kottler, Marie-Laure] CHU Caen, Reference Ctr Rare Disorders Calcium & Phosphorus, Dept Genet, F-14000 Caen, France. [Maupetit-Mehouas, Stephanie; Grybek, Virginie; Linglart, Agnes] Hop Bicetre, AP HP, Reference Ctr Rare Disorders Mineral Metab, Paediat Endocrinol & Diabetol, F-94270 Le Kremlin Bicetre, France. Univ Paris 11, Fac Med, F-94270 Le Kremlin Bicetre, France. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu FU National Institutes of Health [RO1 DK46718-20]; Societe Francaise D'endocrinologie; Societe Francaise d'Endocrinologie et Diabetologie Pediatrique FX This work was supported by the National Institutes of Health (RO1 DK46718-20 to H.J.), by the Societe Francaise D'endocrinologie (fellowship grant to S.M.-M.), and by the Societe Francaise d'Endocrinologie et Diabetologie Pediatrique (fellowship grant to V.G.). NR 41 TC 5 Z9 5 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP E623 EP E631 DI 10.1210/jc.2014-4047 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500016 PM 25603460 ER PT J AU Zhu, J Choa, REY Guo, MH Plummer, L Buck, C Palmert, MR Hirschhorn, JN Seminara, SB Chan, YM AF Zhu, Jia Choa, Ruth E. -Y. Guo, Michael H. Plummer, Lacey Buck, Cassandra Palmert, Mark R. Hirschhorn, Joel N. Seminara, Stephanie B. Chan, Yee-Ming TI A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONSTITUTIONAL DELAY; KALLMANN-SYNDROME; ACTIVATING MUTATIONS; HORMONE DEFICIENCY; GROWTH; VARIANTS; PATTERNS; BOYS; ASSOCIATION; INHERITANCE AB Context: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. Objective: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. Subjects and Outcome Measures: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. Results: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. Conclusions: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. C1 [Zhu, Jia; Choa, Ruth E. -Y.; Plummer, Lacey; Buck, Cassandra; Seminara, Stephanie B.; Chan, Yee-Ming] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Zhu, Jia; Choa, Ruth E. -Y.; Plummer, Lacey; Buck, Cassandra; Seminara, Stephanie B.; Chan, Yee-Ming] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Guo, Michael H.; Hirschhorn, Joel N.; Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Guo, Michael H.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Guo, Michael H.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Palmert, Mark R.] Hosp Sick Children, Div Endocrinol, Toronto, ON M5G 1X8, Canada. [Palmert, Mark R.] Hosp Sick Children, Genet & Genome Biol Program, Toronto, ON M5G 1X8, Canada. [Palmert, Mark R.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada. [Palmert, Mark R.] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A8, Canada. [Palmert, Mark R.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. RP Chan, YM (reprint author), Boston Childrens Hosp, 333 Longwood Ave,Sixth Floor, Boston, MA 02115 USA. EM yee-ming.chan@childrens.harvard.edu FU National Heart, Lung, and Blood Institute (NHLBI); NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926]; Doris Duke Charitable Foundation Clinical Scientist Development Award [U54 HD028138, R01 HD048960, M01RR002172, K23 RR15544, M01 RR000080]; March of Dimes [6-FY12-393]; Charles H. Hood Foundation Child Health Research Award; National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12 HD052896]; [R01 HD043341]; [K24 HD 067388] FX We thank the following physicians for referring subjects: Melissa Buryk, Ayse Pinar Cemeroglu, Olga Hardy, Susan Kirsch, Abhishek Kulkarni, Veronica Mericq, Paulina M. Merino, Daniel Metzger, J.B. Quintos, Michael Racine, Jose Perez-Rodriguez, Karen Rubin, Menachem Samuel Shapiro, David Schwartz, Phyllis Speiser, Pamela Taxel, and Charles Verge. We thank Matthew Chase for his assistance with Sanger sequencing, Stephanie Hadley for her assistance with ascertainment of pedigrees, and Ines Sedlmeyer for her management of the Boston Children's Hospital cohort. We thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. We also acknowledge the support of the National Heart, Lung, and Blood Institute (NHLBI) and the contributions of the research institutions, study investigators, field staff, and study participants in creating the Grand Opportunity Exome Sequencing Project (GO ESP) for biomedical research. Funding for GO ESP was provided by NHLBI Grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO) and RC2 HL-102924 (WHISP), with exome sequencing performed through NHLBI Grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO).; This work was supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award to Y.-M.C., U54 HD028138 to S.B.S., R01 HD048960 to M.R.P and J.N.H., M01 RR002172 to the Boston Children's Hospital General Clinical Research Center (GCRC), and K23 RR15544 and M01RR000080 to the William Dahms GCRC at University Hospitals Cleveland. M.H.G. was supported by March of Dimes Grant 6-FY12-393 to J.N.H. Y.-M.C. was supported by a Charles H. Hood Foundation Child Health Research Award and National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant K12 HD052896 (PI Fleisher). S.B.S. was additionally supported by R01 HD043341 and K24 HD 067388. NR 41 TC 8 Z9 8 U1 1 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2015 VL 100 IS 4 BP E646 EP E654 DI 10.1210/jc.2015-1080 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5UN UT WOS:000353361500019 PM 25636053 ER PT J AU Agboola, S Jethwani, K Khateeb, K Moore, S Kvedar, J AF Agboola, Stephen Jethwani, Kamal Khateeb, Kholoud Moore, Stephanie Kvedar, Joseph TI Heart Failure Remote Monitoring: Evidence From the Retrospective Evaluation of a Real-World Remote Monitoring Program SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE heart failure; telemonitoring; remote monitoring; self-management; hospitalizations; mortality ID STRUCTURED TELEPHONE SUPPORT; HOSPITAL DISCHARGE; METAANALYSIS; MANAGEMENT; ASSOCIATION; OUTCOMES; DISEASE; COHORT; TRIAL AB Background: Given the magnitude of increasing heart failure mortality, multidisciplinary approaches, in the form of disease management programs and other integrative models of care, are recommended to optimize treatment outcomes. Remote monitoring, either as structured telephone support or telemonitoring or a combination of both, is fast becoming an integral part of many disease management programs. However, studies reporting on the evaluation of real-world heart failure remote monitoring programs are scarce. Objective: This study aims to evaluate the effect of a heart failure telemonitoring program, Connected Cardiac Care Program (CCCP), on hospitalization and mortality in a retrospective database review of medical records of patients with heart failure receiving care at the Massachusetts General Hospital. Methods: Patients enrolled in the CCCP heart failure monitoring program at the Massachusetts General Hospital were matched 1:1 with usual care patients. Control patients received care from similar clinical settings as CCCP patients and were identified from a large clinical data registry. The primary endpoint was all-cause mortality and hospitalizations assessed during the 4-month program duration. Secondary outcomes included hospitalization and mortality rates (obtained by following up on patients over an additional 8 months after program completion for a total duration of 1 year), risk for multiple hospitalizations and length of stay. The Cox proportional hazard model, stratified on the matched pairs, was used to assess primary outcomes. Results: A total of 348 patients were included in the time-to-event analyses. The baseline rates of hospitalizations prior to program enrollment did not differ significantly by group. Compared with controls, hospitalization rates decreased within the first 30 days of program enrollment: hazard ratio (HR)=0.52, 95% CI 0.31-0.86, P=.01). The differential effect on hospitalization rates remained consistent until the end of the 4-month program (HR=0.74, 95% CI 0.54-1.02, P=.06). The program was also associated with lower mortality rates at the end of the 4-month program: relative risk (RR)=0.33, 95% 0.11-0.97, P=.04). Additional 8-months follow-up following program completion did not show residual beneficial effects of the CCCP program on mortality (HR=0.64, 95% 0.34-1.21, P=.17) or hospitalizations (HR=1.12, 95% 0.90-1.41, P=.31). Conclusions: CCCP was associated with significantly lower hospitalization rates up to 90 days and significantly lower mortality rates over 120 days of the program. However, these effects did not persist beyond the 120-day program duration. C1 [Agboola, Stephen; Jethwani, Kamal; Moore, Stephanie; Kvedar, Joseph] Partners Healthcare Ctr Connected Hlth, Connected Hlth Innovat, Boston, MA 02128 USA. [Agboola, Stephen; Jethwani, Kamal; Moore, Stephanie; Kvedar, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Agboola, Stephen; Jethwani, Kamal; Moore, Stephanie; Kvedar, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Khateeb, Kholoud] Northeastern Univ, Boston, MA 02115 USA. RP Agboola, S (reprint author), Partners Healthcare Ctr Connected Hlth, Connected Hlth Innovat, 25 New Chardon St,Suite 300, Boston, MA 02128 USA. EM sagboola@mgh.harvard.edu NR 23 TC 2 Z9 2 U1 2 U2 5 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD APR PY 2015 VL 17 IS 4 AR e101 DI 10.2196/jmir.4417 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CH3KC UT WOS:000353928600007 PM 25903278 ER PT J AU Alkire, BC Shrime, MG Dare, AJ Vincent, JR Meara, JG AF Alkire, Blake C. Shrime, Mark G. Dare, Anna J. Vincent, Jeffrey R. Meara, John G. TI Global economic consequences of selected surgical diseases: a modelling study SO LANCET GLOBAL HEALTH LA English DT Article ID MIDDLE-INCOME COUNTRIES; SYSTEMATIC ANALYSIS; COST-EFFECTIVENESS; BURDEN; HEALTH; MORTALITY; SURGERY; INFANT AB Background The surgical burden of disease is substantial, but little is known about the associated economic consequences. We estimate the global macroeconomic impact of the surgical burden of disease due to injury, neoplasm, digestive diseases, and maternal and neonatal disorders from two distinct economic perspectives. Methods We obtained mortality rate estimates for each disease for the years 2000 and 2010 from the Institute of Health Metrics and Evaluation Global Burden of Disease 2010 study, and estimates of the proportion of the burden of the selected diseases that is surgical from a paper by Shrime and colleagues. We first used the value of lost output (VLO) approach, based on the WHO's Projecting the Economic Cost of Ill-Health (EPIC) model, to project annual market economy losses due to these surgical diseases during 2015-30. EPIC attempts to model how disease affects a country's projected labour force and capital stock, which in turn are related to losses in economic output, or gross domestic product (GDP). We then used the value of lost welfare (VLW) approach, which is conceptually based on the value of a statistical life and is inclusive of non-market losses, to estimate the present value of long-run welfare losses resulting from mortality and short-run welfare losses resulting from morbidity incurred during 2010. Sensitivity analyses were performed for both approaches. Findings During 2015-30, the VLO approach projected that surgical conditions would result in losses of 1.25% of potential GDP, or $20.7 trillion (2010 US$, purchasing power parity) in the 128 countries with data available. When expressed as a proportion of potential GDP, annual GDP losses were greatest in low-income and middle-income countries, with up to a 2.5% loss in output by 2030. When total welfare losses are assessed (VLW), the present value of economic losses is estimated to be equivalent to 17% of 2010 GDP, or $14.5 trillion in the 175 countries assessed with this approach. Neoplasm and injury account for greater than 95% of total economic losses with each approach, but maternal, digestive, and neonatal disorders, which represent only 4% of losses in high-income countries with the VLW approach, contribute to 26% of losses in low-income countries. Interpretation The macroeconomic impact of surgical disease is substantial and inequitably distributed. When paired with the growing number of favourable cost-effectiveness analyses of surgical interventions in low-income and middle-income countries, our results suggest that building surgical capacity should be a global health priority. C1 [Alkire, Blake C.; Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Alkire, Blake C.; Shrime, Mark G.; Meara, John G.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA USA. [Alkire, Blake C.; Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Cambridge, MA 02138 USA. [Dare, Anna J.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Dare, Anna J.] Kings Coll London, London WC2R 2LS, England. [Vincent, Jeffrey R.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Vincent, Jeffrey R.] Duke Univ, Sanford Sch Publ Policy, Durham, NC USA. [Meara, John G.] Boston Childrens Hosp, Dept Plast & Reconstruct Surg, Boston, MA USA. RP Alkire, BC (reprint author), 243 Charles St, Boston, MA 02114 USA. EM blakealkire@gmail.com FU US National Institutes of Health/National Cancer Institute FX US National Institutes of Health/National Cancer Institute. NR 36 TC 16 Z9 16 U1 9 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD APR PY 2015 VL 3 SU 2 BP S21 EP S27 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG9GY UT WOS:000353624100009 PM 25926317 ER PT J AU Shrime, MG Bickler, SW Alkire, BC Mock, C AF Shrime, Mark G. Bickler, Stephen W. Alkire, Blake C. Mock, Charlie TI Global burden of surgical disease: an estimation from the provider perspective SO LANCET GLOBAL HEALTH LA English DT Letter ID SURGERY C1 [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02138 USA. [Shrime, Mark G.; Alkire, Blake C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02138 USA. [Shrime, Mark G.; Alkire, Blake C.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Bickler, Stephen W.] Univ Calif San Diego, Dept Surg, Div Pediat Surg, Rady Childrens Hosp, San Diego, CA 92103 USA. [Mock, Charlie] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Mock, Charlie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Mock, Charlie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Shrime, MG (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02138 USA. EM shrime@mail.harvard.edu NR 7 TC 33 Z9 33 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD APR PY 2015 VL 3 SU 2 BP S8 EP S9 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG9GY UT WOS:000353624100005 PM 25926322 ER PT J AU Shrime, MG Dare, AJ Alkire, BC O'Neill, K Meara, JG AF Shrime, Mark G. Dare, Anna J. Alkire, Blake C. O'Neill, Kathleen Meara, John G. TI Catastrophic expenditure to pay for surgery worldwide: a modelling study SO LANCET GLOBAL HEALTH LA English DT Article ID OF-POCKET EXPENDITURE; GLOBAL HEALTH; CARE; MANAGEMENT; HOUSEHOLDS; DELIVERY; SERVICES; BURDEN; INDIA; DELHI AB Background Approximately 150 million individuals worldwide face catastrophic expenditure each year from medical costs alone, and the non-medical costs of accessing care increase that number. The proportion of this expenditure related to surgery is unknown. Because the World Bank has proposed elimination of medical impoverishment by 2030, the effect of surgical conditions on financial catastrophe should be quantified so that any financial risk protection mechanisms can appropriately incorporate surgery. Methods To estimate the global incidence of catastrophic expenditure due to surgery, we built a stochastic model. The income distribution of each country, the probability of requiring surgery, and the medical and non-medical costs faced for surgery were incorporated. Sensitivity analyses were run to test the robustness of the model. Findings 3 . 7 billion people (posterior credible interval 3 . 2-4 . 2 billion) risk catastrophic expenditure if they need surgery. Each year, 81 . 3 million people (80 . 8-81 . 7 million) worldwide are driven to financial catastrophe-32 . 8 million (32 . 4-33 . 1 million) from the costs of surgery alone and 48 . 5 million (47 . 7-49 . 3) from associated non-medical costs. The burden of catastrophic expenditure is highest in countries of low and middle income; within any country, it falls on the poor. Estimates were sensitive to the definition of catastrophic expenditure and the costs of care. The inequitable burden distribution was robust to model assumptions. Interpretation Half the global population is at risk of financial catastrophe from surgery. Each year, surgical conditions cause 81 million individuals to face catastrophic expenditure, of which less than half is attributable to medical costs. These findings highlight the need for financial risk protection for surgery in health-system design. C1 [Shrime, Mark G.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Dare, Anna J.] Kings Coll London, Kings Hlth Partners, Kings Ctr Global Hlth, London WC2R 2LS, England. [Shrime, Mark G.; Alkire, Blake C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shrime, Mark G.; Alkire, Blake C.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [O'Neill, Kathleen] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Shrime, Mark G.; Alkire, Blake C.; Meara, John G.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA USA. [Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. RP Shrime, MG (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM shrime@mail.harvard.edu FU NIH/NCI [R25CA92203] FX MGS received partial funding from NIH/NCI R25CA92203. NR 43 TC 18 Z9 18 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD APR PY 2015 VL 3 SU 2 BP S38 EP S44 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG9GY UT WOS:000353624100011 PM 25926319 ER PT J AU Verguet, S Alkire, BC Bickler, SW Lauer, JA Uribe-Leitz, T Molina, G Weiser, TG Yamey, G Shrime, MG AF Verguet, Stephane Alkire, Blake C. Bickler, Stephen W. Lauer, Jeremy A. Uribe-Leitz, Tarsicio Molina, George Weiser, Thomas G. Yamey, Gavin Shrime, Mark G. TI Timing and cost of scaling up surgical services in low-income and middle-income countries from 2012 to 2030: a modelling study SO LANCET GLOBAL HEALTH LA English DT Article ID GLOBAL BURDEN; SYSTEMATIC ANALYSIS; SUSTAINABLE DEVELOPMENT; SURGERY; HEALTH; MORTALITY; INJURIES; DISEASE; TUBERCULOSIS; DECLINE AB Background Given the large burden of surgical conditions and the crosscutting nature of surgery, scale-up of basic surgical services is crucial to health-system strengthening. The Lancet Commission on Global Surgery proposed that, to meet populations' needs, countries should achieve 5000 major operations per 100 000 population per year. We modelled the possible scale-up of surgical services in 88 low-income and middle-income countries with a population greater than 1 million from 2012 to 2030 at various rates and quantified the associated costs. Methods Major surgery includes any intervention within an operating room involving tissue manipulation and anaesthesia. We used estimates for the number of major operations achieved per country annually and the number of operating rooms per region, and data from Mongolia and Mexico for trends in the number of operations. Unit costs included a cost per operation, proxied by caesarean section cost estimates; hospital construction data were used to estimate cost per operating room construction. We determined the year by which each country would achieve the Commission's target. We modelled three scenarios for the scale-up rate: actual rates (5.1% per year) and two "aspirational" rates, the rates achieved by Mongolia (8.9% annual) and Mexico (22.5% annual). We subsequently estimated the associated costs. Findings About half of the 88 countries would achieve the target by 2030 at actual rates of improvements, with up to two-thirds if the rate were increased to Mongolian rates. We estimate the total costs of achieving scale-up at US$ 300-420 billion (95% UI 190-600 billion) over 2012-30, which represents 4-8% of total annual health expenditures among low-income and lower middle-income countries and 1% among upper middle-income countries. Interpretation Scale-up of surgical services will not reach the target of 5000 operations per 100 000 by 2030 in about half of low-income and middle-income countries without increased funding, which countries and the international community must seek to achieve expansion of quality surgical services. C1 [Verguet, Stephane] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Alkire, Blake C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Alkire, Blake C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg, Boston, MA USA. [Bickler, Stephen W.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Lauer, Jeremy A.] WHO, CH-1211 Geneva, Switzerland. [Uribe-Leitz, Tarsicio; Weiser, Thomas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Molina, George] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Molina, George] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02115 USA. [Molina, George; Shrime, Mark G.] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Yamey, Gavin] Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Boston, MA USA. RP Verguet, S (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave, Boston, MA 02115 USA. EM verguet@hsph.harvard.edu FU Lancet Commission on Global Surgery FX This study was undertaken under the auspices of The Lancet Commission on Global Surgery. This work would not have been accomplished without the commitment of many people. In particular, we are indebted to Anna Dare, Sarah Greenberg, Russell Gruen, Lars Hagander, Hampus Holmer, John Meara, Charlie Mock, Johanna Riesel, and John Rose. We also thank Elizabeth Johnson and Joseph Dieleman at the Institute for Health Metrics and Evaluation for helpful conversations. NR 47 TC 4 Z9 5 U1 5 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD APR PY 2015 VL 3 SU 2 BP S28 EP S37 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG9GY UT WOS:000353624100010 PM 25926318 ER PT J AU Morrison, VA Jung, SH Johnson, J LaCasce, A Blum, KA Bartlett, NL Pitcher, BN Cheson, BD AF Morrison, Vicki A. Jung, Sin-Ho Johnson, Jeffrey LaCasce, Ann Blum, Kristie A. Bartlett, Nancy L. Pitcher, Brandelyn N. Cheson, Bruce D. TI Therapy with bortezomib plus lenalidomide for relapsed/refractory mantle cell lymphoma: final results of a phase II trial (CALGB 50501) SO LEUKEMIA & LYMPHOMA LA English DT Article DE Mantle cell lymphoma; bortezomib; lenalidomide ID NON-HODGKINS-LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; SINGLE-AGENT LENALIDOMIDE; CLINICAL-TRIALS; B-CELL; UNITED-STATES; RITUXIMAB; MULTICENTER; INDOLENT; MONOTHERAPY AB Cancer and Leukemia Group B designed a phase II trial of lenalidomide + bortezomib for relapsed/refractory mantle cell lymphoma (MCL). Induction therapy was lenalidomide (days 1-14) plus bortezomib (days 1/4/8/11), every 21 days for eight cycles. Complete/partial responders (CR, PR) received maintenance lenalidomide (days 1-14) and bortezomib (days 1/8), every 21 days. Primary endpoint was overall response rate; secondary endpoints were CR rate, progression-free (PFS), event-free (EFS) and overall survival (OS). Fifty-three eligible patients, median age 67 years, were accrued. Median number of cycles received was 4 (range, 1-82). Median followup was 46 (range, 12-67) months. Best response was CR 15%, PR 25%. 5/8 CR, and 4/13 PR patients received maintenance. Six CR and one PR patient remain in remission (median, 3.2 years). Thirty-three (62%) patients have died. One-year PFS, EFS and OS are 40%, 25% and 68%, respectively. This combination will not be pursued further. C1 [Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN 55417 USA. [Morrison, Vicki A.] VAMC, Minneapolis, MN 55417 USA. [Jung, Sin-Ho; Johnson, Jeffrey; Pitcher, Brandelyn N.] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Blum, Kristie A.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. [Cheson, Bruce D.] Georgetown Univ Hosp, Washington, DC 20007 USA. RP Morrison, VA (reprint author), Univ Minnesota, Med, One Vet Dr, Minneapolis, MN 55417 USA. EM morri002@umn.edu FU National Cancer Institute [CA31946, CA33601] FX The research for CALGB 50501 (Alliance) was supported, in part, by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 35 TC 9 Z9 9 U1 2 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2015 VL 56 IS 4 BP 958 EP 964 DI 10.3109/10428194.2014.938333 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA CG9CT UT WOS:000353612700022 PM 24996441 ER PT J AU Jacobsen, E Pozdnyakova, O Redd, R Fisher, DC Dorfman, DM Dal Cin, P LaCasce, A Armand, P Hochberg, E Cote, G Shahsafaei, A Neuberg, D Brown, JR Freedman, AS AF Jacobsen, Eric Pozdnyakova, Olga Redd, Robert Fisher, David C. Dorfman, David M. Dal Cin, Paola LaCasce, Ann Armand, Philippe Hochberg, Ephraim Cote, Gregory Shahsafaei, Ali Neuberg, Donna Brown, Jennifer R. Freedman, Arnold S. TI Imatinib mesylate lacks efficacy in relapsed/refractory peripheral T cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE Lymphoma; imatinib; PDGFR-alpha ID C-KIT EXPRESSION AB Platelet derived growth factor-alpha (PDGFR-alpha) is expressed in peripheral T cell lymphoma, not otherwise specified (PTCL, NOS). Imatinib mesylate demonstrated in vitro cytotoxicity against primary PTCL,NOS cells. We initiated a trial of imatinib in 12 patients with relapsed or refractory T-cell non-Hodgkin lymphoma (T-NHL). PDGFR-alpha expression by immunohistochemistry and fluorescence in situ hybridization (FISH) to assess for FIP1L1-PDGFR-alpha fusion and/or PDGFR-alpha amplification were not required for study entry. We documented no objective responses. The median progression-free survival was 21.0 days (90% confidence interval [Cl] 15.0, 28.0) and median overall survival was 154 days (90% Cl 35, 242). Four patients had tissue available for analysis of PDGFR-a by immunohistochemistry and three of these patients' tumors expressed PDGFR-alpha. Imatinib was not effective for the treatment of peripheral T cell lymphoma in an unselected group of patients in which PDGFR-alpha expression was not required for study entry. C1 [Jacobsen, Eric; Fisher, David C.; LaCasce, Ann; Armand, Philippe; Brown, Jennifer R.; Freedman, Arnold S.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02215 USA. [Redd, Robert; Neuberg, Donna] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02215 USA. [Pozdnyakova, Olga; Dorfman, David M.; Dal Cin, Paola; Shahsafaei, Ali] Brigham & Womens Hosp, Pathol, Boston, MA 02115 USA. [Hochberg, Ephraim] Massachusetts Gen Hosp, Ctr Lymphoma, Boston, MA 02114 USA. [Cote, Gregory] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. RP Jacobsen, E (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave,Mayer 219, Boston, MA 02215 USA. EM Eric_Jacobsen@dfci.harvard.edu OI Cote, Gregory/0000-0003-0181-886X NR 13 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2015 VL 56 IS 4 BP 993 EP 998 DI 10.3109/10428194.2014.941835 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA CG9CT UT WOS:000353612700028 PM 25012943 ER PT J AU Qiao, SX Dennis, M Song, XF Vadysirisack, DD Salunke, D Nash, Z Yang, ZF Liesa, M Yoshioka, J Matsuzawa, S Shirihai, OS Lee, RT Reed, JC Ellisen, LW AF Qiao, Shuxi Dennis, Michael Song, Xiufeng Vadysirisack, Douangsone D. Salunke, Devika Nash, Zachary Yang, Zhifen Liesa, Marc Yoshioka, Jun Matsuzawa, Shu-Ichi Shirihai, Orian S. Lee, Richard T. Reed, John C. Ellisen, Leif W. TI A REDD1/TXNIP pro-oxidant complex regulates ATG4B activity to control stress-induced autophagy and sustain exercise capacity SO NATURE COMMUNICATIONS LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; SKELETAL-MUSCLE; IN-VIVO; SUPPRESSES TUMORIGENESIS; ENERGY STRESS; MTOR; HYPOXIA; PROTEIN; REDD1; TXNIP AB Macroautophagy (autophagy) is a critical cellular stress response; however, the signal transduction pathways controlling autophagy induction in response to stress are poorly understood. Here we reveal a new mechanism of autophagy control whose deregulation disrupts mitochondrial integrity and energy homeostasis in vivo. Stress conditions including hypoxia and exercise induce reactive oxygen species (ROS) through upregulation of a protein complex involving REDD1, an mTORC1 inhibitor and the pro-oxidant protein TXNIP. Decreased ROS in cells and tissues lacking either REDD1 or TXNIP increases catalytic activity of the redox-sensitive ATG4B cysteine endopeptidase, leading to enhanced LC3B delipidation and failed autophagy. Conversely, REDD1/TXNIP complex expression is sufficient to induce ROS, suppress ATG4B activity and activate autophagy. In Redd1(-/-) mice, deregulated ATG4B activity and disabled autophagic flux cause accumulation of defective mitochondria, leading to impaired oxidative phosphorylation, muscle ATP depletion and poor exercise capacity. Thus, ROS regulation through REDD1/TXNIP is physiological rheostat controlling stress-induced autophagy. C1 [Qiao, Shuxi; Dennis, Michael; Song, Xiufeng; Vadysirisack, Douangsone D.; Salunke, Devika; Nash, Zachary; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Qiao, Shuxi; Song, Xiufeng; Vadysirisack, Douangsone D.; Yoshioka, Jun; Lee, Richard T.; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yang, Zhifen; Matsuzawa, Shu-Ichi; Reed, John C.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. [Liesa, Marc; Shirihai, Orian S.] Boston Univ, Dept Med, Evans Ctr, Mitochondria ARC,Sch Med, Boston, MA 02118 USA. [Yoshioka, Jun; Lee, Richard T.] Brigham & Womens Hosp, Regenerat Med Ctr, Boston, MA 02115 USA. [Shirihai, Orian S.] Ben Gurion Univ Negev, Dept Clin Biochem, Fac Med, IL-8410501 Beer Sheva, Israel. [Reed, John C.] Roche Pharmaceut Res & Early Dev, CH-4070 Basel, Switzerland. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM lellisen@mgh.harvard.edu OI Liesa Roig, Marc/0000-0002-5909-8570 FU Fundacion Ramon Areces; T.J. Martell Foundation; [R01 CA122589]; [F32 CA150633]; [R01 HL103582] FX We thank Mary McKee and the Microscopy Core of the Program in Membrane Biology (PMB) at MGH for help with electron microscopy, Eileen White (Rutgers University) for ATG7-deficient cells and members of the Ellisen and Bardeesy laboratories for helpful comments on the manuscript. M.L. is an Evans Center Fellow and was the recipient of a postdoctoral fellowship from Fundacion Ramon Areces. This work was supported by R01 CA122589 (L.W.E., S.Q., X.S., M.D. and D.S.), by F32 CA150633 (D.D.V.), R01 HL103582 (R.T.L. and J.Y.) and by the T.J. Martell Foundation. NR 58 TC 26 Z9 27 U1 6 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 7014 DI 10.1038/ncomms8014 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0JR UT WOS:000353706300001 PM 25916556 ER PT J AU Satpathy, SR Jala, VR Bodduluri, SR Krishnan, E Hegde, B Hoyle, GW Fraig, M Luster, AD Haribabu, B AF Satpathy, Shuchismita R. Jala, Venkatakrishna R. Bodduluri, Sobha R. Krishnan, Elangovan Hegde, Bindu Hoyle, Gary W. Fraig, Mostafa Luster, Andrew D. Haribabu, Bodduluri TI Crystalline silica-induced leukotriene B-4-dependent inflammation promotes lung tumour growth SO NATURE COMMUNICATIONS LA English DT Article ID CANCER-RELATED INFLAMMATION; NALP3 INFLAMMASOME; ALVEOLAR MACROPHAGES; NEUTROPHIL ELASTASE; C57BL/6 MICE; B-4 RECEPTOR; MAST-CELLS; ACTIVATION; TUMORIGENESIS; EXPOSURE AB Chronic exposure to crystalline silica (CS) causes silicosis, an irreversible lung inflammatory disease that may eventually lead to lung cancer. In this study, we demonstrate that in K-ras(LA1) mice, CS exposure markedly enhances the lung tumour burden and genetic deletion of leukotriene B4 receptor-1 (BLT1(-/-)) attenuates this increase. Pulmonary neutrophilic inflammation induced by CS is significantly reduced in BLT1(-/-) K-ras(LA1) mice. CS exposure induces LTB4 production by mast cells and macrophages independent of inflammasome activation. In an air-pouch model, CS-induced neutrophil recruitment is dependent on LTB4 production by mast cells and BLT1 expression on neutrophils. In an implantable lung tumour model, CS exposure results in rapid tumour growth and decreased survival that is attenuated in the absence of BLT1. These results suggest that the LTB4/BLT1 axis sets the pace of CS-induced sterile inflammation that promotes lung cancer progression. This knowledge may facilitate development of immunotherapeutic strategies to fight silicosis and lung cancer. C1 [Satpathy, Shuchismita R.; Jala, Venkatakrishna R.; Bodduluri, Sobha R.; Krishnan, Elangovan; Hegde, Bindu; Haribabu, Bodduluri] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA. [Satpathy, Shuchismita R.; Jala, Venkatakrishna R.; Bodduluri, Sobha R.; Krishnan, Elangovan; Hegde, Bindu; Haribabu, Bodduluri] Univ Louisville, Dept Microbiol & Immunol, Louisville, KY 40202 USA. [Hoyle, Gary W.] Univ Louisville, Dept Environm & Occupat Hlth Sci, Louisville, KY 40202 USA. [Fraig, Mostafa] Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40202 USA. [Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Med Sch, Boston, MA USA. RP Haribabu, B (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA. RI Fraig, Mostafa/I-1670-2016; OI Fraig, Mostafa/0000-0003-1119-3672; Bodduluri, Haribabu/0000-0002-8261-3294 FU NIH [R01CA138623, NIH: 1P30GM106396-01]; Kentucky Lung Cancer Research Board; James Graham Brown foundation FX We thank Dr Jason Chesney for critical reading of the manuscript. This work was supported by the NIH grant R01CA138623, NIH: 1P30GM106396-01 (UofL JG Brown Cancer Center Phase III CoBRE) and by research grants from the Kentucky Lung Cancer Research Board as well as Institutional support from the James Graham Brown Cancer Center. Dr Satpathy is supported by a postdoctoral award from the James Graham Brown foundation. NR 53 TC 13 Z9 14 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 7064 DI 10.1038/ncomms8064 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0KG UT WOS:000353707800002 PM 25923988 ER PT J AU Zhang, CZ Adalsteinsson, VA Francis, J Cornils, H Jung, J Maire, C Ligon, KL Meyerson, M Love, JC AF Zhang, Cheng-Zhong Adalsteinsson, Viktor A. Francis, Joshua Cornils, Hauke Jung, Joonil Maire, Cecile Ligon, Keith L. Meyerson, Matthew Love, J. Christopher TI Calibrating genomic and allelic coverage bias in single-cell sequencing SO NATURE COMMUNICATIONS LA English DT Article ID CIRCULATING TUMOR-CELLS; COPY NUMBER VARIATION; DISPLACEMENT AMPLIFICATION; POLYMERASE CLONING; SAMPLES; CANCER; RECOMBINATION; EVOLUTION; MUTATION; SPERM AB Artifacts introduced in whole-genome amplification (WGA) make it difficult to derive accurate genomic information from single-cell genomes and require different analytical strategies from bulk genome analysis. Here, we describe statistical methods to quantitatively assess the amplification bias resulting from whole-genome amplification of single-cell genomic DNA. Analysis of single-cell DNA libraries generated by different technologies revealed universal features of the genome coverage bias predominantly generated at the amplicon level (1-10 kb). The magnitude of coverage bias can be accurately calibrated from low-pass sequencing (similar to 0.1 x) to predict the depth-of-coverage yield of single-cell DNA libraries sequenced at arbitrary depths. We further provide a benchmark comparison of single-cell libraries generated by multi-strand displacement amplification (MDA) and multiple annealing and looping-based amplification cycles (MALBAC). Finally, we develop statistical models to calibrate allelic bias in single-cell whole-genome amplification and demonstrate a census-based strategy for efficient and accurate variant detection from low-input biopsy samples. C1 [Zhang, Cheng-Zhong; Francis, Joshua; Maire, Cecile; Ligon, Keith L.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Zhang, Cheng-Zhong; Adalsteinsson, Viktor A.; Francis, Joshua; Jung, Joonil; Meyerson, Matthew; Love, J. Christopher] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. [Adalsteinsson, Viktor A.; Love, J. Christopher] MIT, Dept Chem Engn Cambridge, Cambridge, MA 02139 USA. [Adalsteinsson, Viktor A.; Love, J. Christopher] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Cornils, Hauke] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Cornils, Hauke] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Ligon, Keith L.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Matthew_Meyerson@dfci.harvard.edu; clove@mit.edu FU National Cancer Institute [U24CA143867]; National Science Foundation; Koch Institute for Integrative Cancer Research at MIT; Dana-Farber/Harvard Cancer Center (DF/HCC); National Brain Tumor Society; Janssen Pharmaceuticals, Inc.; Koch Institute Support (core) Grant from the National Cancer Institute. [P30-CA14051] FX We thank Dr David Pellman for sharing the sequencing data on RPE cells, M. Leibowitz, X. Cai and G. Evrony for discussions, and the Koch Institute Swanson Biotechnology Center (specifically the BioMicro Center) for technical support. C.-Z.Z. was supported by the National Cancer Institute (U24CA143867 to M. M.). V.A.A. was supported, in part, by a graduate fellowship from the National Science Foundation. J.C.L. is a Camille Dreyfus Teacher-Scholar. This work was supported by the Bridge Project, a collaboration between Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center (DF/HCC) to (J.C.L., K.L.L. and M. M.) and the National Brain Tumor Society. This work was also supported in part by Janssen Pharmaceuticals, Inc. and the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. NR 35 TC 10 Z9 11 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6822 DI 10.1038/ncomms7822 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IO UT WOS:000353703200001 PM 25879913 ER PT J AU Nicholson, KA Cudkowicz, ME Berry, JD AF Nicholson, Katharine A. Cudkowicz, Merit E. Berry, James D. TI Clinical Trial Designs in Amyotrophic Lateral Sclerosis: Does One Design Fit All? SO NEUROTHERAPEUTICS LA English DT Review DE Antisense oligonucleotide; induced pluripotent stem cell; continual reassessment model; futility design; selection design; historical placebo ID CONTINUAL REASSESSMENT METHOD; URIC-ACID LEVELS; VOLUNTARY ISOMETRIC CONTRACTION; ELECTRICAL-IMPEDANCE MYOGRAPHY; MEASURING MUSCLE STRENGTH; REGULATORY T-LYMPHOCYTES; UNIT NUMBER ESTIMATION; PHASE-I TRIALS; SUBUNIT PNF-H; ANTISENSE OLIGONUCLEOTIDE AB The last 2 decades have seen a surge in the number of amyotrophic lateral sclerosis (ALS) clinical trials with the hope of finding successful treatments. Clinical trialists aim to repurpose existing drugs and test novel compounds to target potential ALS disease pathophysiology. Recent technological advancements have led to the discovery of new causative genetic agents and modes of delivering potential therapy, calling for increasingly sophisticated trial design. The standard ALS clinical trial design may be modified depending on study needs: type of therapy; route of therapy delivery; phase of therapy development; applicable subpopulation; market availability of therapy; and utility of telemedicine. Novel biomarkers of diagnostic, predictive, prognostic, and pharmacodynamic value are undergoing development and validation for use in clinical trials. Design modifications build on the traditional clinical trial design and may be employed in either the learning or confirming trial phase. Novel designs aim to minimize patient risk, study duration, and sample size, while improving efficiency and promoting statistical power to herald an exciting era for clinical research in ALS. C1 [Nicholson, Katharine A.; Cudkowicz, Merit E.; Berry, James D.] Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Res Inst, Boston, MA 02114 USA. RP Nicholson, KA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Res Inst, 165 Cambridge St,Suite 600, Boston, MA 02114 USA. EM knicholson@partners.org NR 80 TC 7 Z9 7 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD APR PY 2015 VL 12 IS 2 BP 376 EP 383 DI 10.1007/s13311-015-0341-2 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CG4AS UT WOS:000353223000009 PM 25700798 ER PT J AU Zach, N Ennist, DL Taylor, AA Alon, H Sherman, A Kueffner, R Walker, J Sinani, E Katsovskiy, I Cudkowicz, M Leitner, ML AF Zach, Neta Ennist, David L. Taylor, Albert A. Alon, Hagit Sherman, Alexander Kueffner, Robert Walker, Jason Sinani, Ervin Katsovskiy, Igor Cudkowicz, Merit Leitner, Melanie L. TI Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS? SO NEUROTHERAPEUTICS LA English DT Review DE Amyotrophic lateral sclerosis; Disease progression; Patient stratification; Clinical trial database; Clinical trial simulation ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; FUNCTIONAL RATING-SCALE; URIC-ACID LEVELS; DISEASE PROGRESSION; PROGNOSTIC-FACTORS; OUTCOME MEASURES; SURVIVAL; POPULATION; PREDICTORS AB Advancing research and clinical care, and conducting successful and cost-effective clinical trials requires characterizing a given patient population. To gather a sufficiently large cohort of patients in rare diseases such as amyotrophic lateral sclerosis (ALS), we developed the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) platform. The PRO-ACT database currently consists of > 8600 ALS patient records from 17 completed clinical trials, and more trials are being incorporated. The database was launched in an open-access mode in December 2012; since then, > 400 researchers from > 40 countries have requested the data. This review gives an overview on the research enabled by this resource, through several examples of research already carried out with the goal of improving patient care and understanding the disease. These examples include predicting ALS progression, the simulation of future ALS clinical trials, the verification of previously proposed predictive features, the discovery of novel predictors of ALS progression and survival, the newly identified stratification of patients based on their disease progression profiles, and the development of tools for better clinical trial recruitment and monitoring. Results from these approaches clearly demonstrate the value of large datasets for developing a better understanding of ALS natural history, prognostic factors, patient stratification, and more. The increasing use by the community suggests that further analyses of the PRO-ACT database will continue to reveal more information about this disease that has for so long defied our understanding. C1 [Zach, Neta; Alon, Hagit] Prize4Life, Tel Aviv, Israel. [Ennist, David L.; Taylor, Albert A.] Origent Data Sci Inc, Vienna, VA USA. [Sherman, Alexander; Walker, Jason; Sinani, Ervin; Katsovskiy, Igor; Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Res Inst, Charlestown, MA USA. [Kueffner, Robert] Helmholtz Zentrum, Munich, Germany. [Leitner, Melanie L.] Biogen Idec Inc, Cambridge, MA USA. RP Zach, N (reprint author), Prize4Life, Tel Aviv, Israel. EM nzach@Prize4Life.org FU ALS Therapy Alliance (ATA) FX We thank our partners in this project, Prize4Life, the Neurological Clinical Research Institute at Massachusetts General Hospital and NEALS ALS consortium for bringing PRO-ACT to life. We also thank the ALS Therapy Alliance (ATA) for funding this project, and the companies and academic institutions that donated clinical trial data. Finally, we would like to thank the many thousands of people with ALS whose participation in ALS clinical trials has created the PRO-ACT platform. NR 57 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD APR PY 2015 VL 12 IS 2 BP 417 EP 423 DI 10.1007/s13311-015-0336-z PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CG4AS UT WOS:000353223000013 PM 25613183 ER PT J AU Ohye, BY Brendel, RW Fredman, SJ Bui, E Rauch, PK Allard, MD Pentel, KZ Simon, NM AF Ohye, Bonnie Y. Brendel, Rebecca W. Fredman, Steffany J. Bui, Eric Rauch, Paula K. Allard, Michael D. Pentel, Kimberly Z. Simon, Naomi M. TI Three-Generation Model: A Family Systems Framework for the Assessment and Treatment of Veterans With Posttraumatic Stress Disorder and Related Conditions SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE PTSD; veteran; family-centered health care; family systems; traumatic brain injury ID PSYCHOLOGICAL DISTRESS; HEALTH-CARE; SYMPTOMS; IRAQ; DEPLOYMENT; PTSD; AFGHANISTAN; CHILDREN; ADJUSTMENT; COUPLES AB This article describes the three-generation family systems health care model developed at the Veteran and Family Clinic of the Home Base Program, a partnership between the Red Sox Foundation and Massachusetts General Hospital designed to improve treatment engagement of veterans with posttraumatic stress disorder (PTSD) and related conditions, and to provide care to the entire military-connected family. This clinical model was designed to address 3 interdependent facets of the PTSD-affected family system: (a) the multiple attachment relationships that are often strained; (b) the veteran's family roles, which may be impaired; and (c) the multiple pathways for treatment engagement and amelioration of the veteran's PTSD-related distress and behaviors within the family system. In addition, we describe the assessment system, designed to probe the interrelationships of individual veteran, couple, parenting, child, and family levels of functioning. Three cases illustrative of the three-generation model's clinical application, how it can address unmet needs, and its ability to overcome barriers to health care for military families are also discussed. C1 [Ohye, Bonnie Y.; Brendel, Rebecca W.; Bui, Eric; Rauch, Paula K.; Allard, Michael D.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Fredman, Steffany J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simon, Naomi M.] Massachusetts Gen Hosp, Complicated Grief Program, Boston, MA 02114 USA. [Ohye, Bonnie Y.] Harvard Univ, Sch Med, Psychol, Cambridge, MA 02138 USA. [Brendel, Rebecca W.; Simon, Naomi M.] Harvard Univ, Sch Med, Psychiat, Cambridge, MA 02138 USA. [Fredman, Steffany J.; Bui, Eric; Rauch, Paula K.; Allard, Michael D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pentel, Kimberly Z.] Univ N Carolina, Chapel Hill, NC USA. RP Ohye, BY (reprint author), Massachusetts Gen Hosp, Red Sox Fdn, Home Base Clin, 101 Merrimac St,Suite 250, Boston, MA 02114 USA. EM bohye@mgh.harvard.edu RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Red Sox Foundation; Massachusetts General Hospital Home Base Program FX WE THANK THE PHILANTHROPIC SUPPORTERS of the Red Sox Foundation and Massachusetts General Hospital Home Base Program, who have supported this work. We would also like to thank all of the staff and clinicians of the Home Base Program (HBP) who have contributed to the development and implementation of this model. Finally, we thank Yang (Karen) Chen for her assistance with the revised manuscript. NR 48 TC 1 Z9 1 U1 1 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD APR PY 2015 VL 46 IS 2 BP 97 EP 106 DI 10.1037/a0037735 PG 10 WC Psychology, Multidisciplinary SC Psychology GA CH3DL UT WOS:000353906700004 ER PT J AU Ma, C Hernandez, MA Kirkpatrick, VE Liang, LJ Nouvong, AL Gordon, IL AF Ma, Christine Hernandez, Michael A. Kirkpatrick, Vincent E. Liang, Li-Jung Nouvong, Aksone L. Gordon, Ian L. TI Topical Platelet-Derived Growth Factor vs Placebo Therapy of Diabetic Foot Ulcers Offloaded With Windowed Casts: A Randomized, Controlled Trial SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article DE diabetic foot ulcer; platelet derived growth factor; diabetes; short leg walking cast ID OFF-LOADING DEVICES; TOTAL CONTACT CAST; LOWER-EXTREMITY; PLANTAR ULCERS; CLINICAL-TRIAL; BEARING CAST; ULCERATION; METAANALYSIS; DEBRIDEMENT; MANAGEMENT AB Objective. This study sought to compare the efficacy of topical platelet derived growth factor (Regranex, Smith and Nephew, London, UK) (test group) to placebo (control group) in treating diabetic foot ulcers. All subjects had a short leg walking cast with a window fashioned in the cast over the site of the ulcer. Methods. Forty-six subjects were randomized (double-blind) 1:1 to the test or control group and treated for up to 4 months. Subjects had Wagner grade I ulcers with wound area of 1 cm(2) to 16 cm(2) without severe peripheral arterial disease, osteomyelitis, or any infection requiring antibiotics. Study medication was applied daily and casts changed approximately every 14 days. Results. Of the 46 subjects randomized, 38 either healed or completed 16 weeks of therapy without healing. Eight subjects dropped out prior to 16 weeks. Based on intention-to-treat, 12 of 23 (52%) test group subjects healed before 16 weeks compared to 13 of 23 (57%) control group subjects (not significant). Regression analysis demonstrated that slower healing was associated with larger initial wound size (hazard radio [HR] = 0.997, 95% confidence interval [Cl]: 0.995-1.00, P = 0.028) and excessive wound drainage (HR = 0.346, 95% CI: 0.126-0.948, P = 0.039). Excluding the patients who dropped out, 25 of 38 (66%) subjects healed by 4 months. Three additional subjects healed with casts that were worn longer than 4 months, for an overall rate of 74% at 9 months. Five subjects developed cast burns, and 3 patients required amputation. Conclusion. Topical platelet derived growth factor does not appear to significantly improve healing of Wagner grade I diabetic foot ulcers that are treated by offloading with a short leg walking cast. Excellent healing rates may be achieved with casting alone. C1 [Ma, Christine; Hernandez, Michael A.; Kirkpatrick, Vincent E.; Gordon, Ian L.] Vet Affairs Long Beach Healthcare Syst, Dept Surg, Long Beach, CA USA. [Kirkpatrick, Vincent E.; Gordon, Ian L.] Univ Calif Irvine, Sch Med, Dept Surg, Orange, CA 92868 USA. [Liang, Li-Jung; Nouvong, Aksone L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Liang, Li-Jung; Nouvong, Aksone L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Nouvong, Aksone L.] Westem Univ Hlth Sci, Pomona, CA USA. RP Kirkpatrick, VE (reprint author), Univ Calif Irvine, Med Ctr, Dept Surg, 333 City Blvd W,Suite 700, Orange, CA 92868 USA. EM kirkpatrickv@uthscsa.edu FU Heritage Medical Research Institute of Heritage Provider Network, Inc, Northridge, CA, a health maintenance organization FX The authors disclose this study was funded by the Heritage Medical Research Institute of Heritage Provider Network, Inc, Northridge, CA, a health maintenance organization whose research arm supports medical research. The sponsor had no influence on the collection and interpretation of data or the writing of the manuscript. NR 26 TC 7 Z9 7 U1 0 U2 5 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 EI 1943-2704 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD APR PY 2015 VL 27 IS 4 BP 83 EP 91 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA CG9XF UT WOS:000353672700002 PM 25855851 ER PT J AU Kouri, FM Hurley, LA Daniel, WL Day, ES Hua, YJ Hao, LL Peng, CY Merkel, TJ Queisser, MA Ritner, C Zhang, HL James, CD Sznajder, JI Chin, L Giljohann, DA Kessler, JA Peter, ME Mirkin, CA Stegh, AH AF Kouri, Fotini M. Hurley, Lisa A. Daniel, Weston L. Day, Emily S. Hua, Youjia Hao, Liangliang Peng, Chian-Yu Merkel, Timothy J. Queisser, Markus A. Ritner, Carissa Zhang, Hailei James, C. David Sznajder, Jacob I. Chin, Lynda Giljohann, David A. Kessler, John A. Peter, Marcus E. Mirkin, Chad A. Stegh, Alexander H. TI miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma SO GENES & DEVELOPMENT LA English DT Article DE miR-182; Bcl2L12; c-Met; HIF2A; glioblastoma; nanotechnology; spherical nucleic acids ID STEM-CELLS; DRUG-DELIVERY; COLON-CANCER; TGF-BETA; PROLIFERATION; BCL2L12; INHIBITION; CARCINOMA; SURVIVAL; P53 AB Glioblastoma multiforme (GBM) is a lethal, therapy-resistant brain cancer consisting of numerous tumor cell subpopulations, including stem-like glioma-initiating cells (GICs), which contribute to tumor recurrence following initial response to therapy. Here, we identified miR-182 as a regulator of apoptosis, growth, and differentiation programs whose expression level is correlated with GBM patient survival. Repression of Bcl2-like12 (Bcl2L12), c-Met, and hypoxia-inducible factor 2a (HIF2A) is of central importance to miR-182 anti-tumor activity, as it results in enhanced therapy susceptibility, decreased GIC sphere size, expansion, and stemness in vitro. To evaluate the tumor-suppressive function of miR-182 in vivo, we synthesized miR-182-based spherical nucleic acids (182-SNAs); i.e., gold nanoparticles covalently functionalized with mature miR-182 duplexes. Intravenously administered 182-SNAs penetrated the blood-brain/blood-tumor barriers (BBB/BTB) in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma, causing reduced tumor burden and increased animal survival. Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM. C1 [Kouri, Fotini M.; Hurley, Lisa A.; Peng, Chian-Yu; Ritner, Carissa; Kessler, John A.; Stegh, Alexander H.] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA. [Kouri, Fotini M.; Hurley, Lisa A.; Peng, Chian-Yu; Ritner, Carissa; Kessler, John A.; Stegh, Alexander H.] Northwestern Univ, Brain Tumor Inst, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Daniel, Weston L.; Giljohann, David A.] AuraSense Therapeut, Skokie, IL 60077 USA. [Day, Emily S.; Hao, Liangliang; Merkel, Timothy J.; Mirkin, Chad A.; Stegh, Alexander H.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. [Day, Emily S.; Hao, Liangliang; Merkel, Timothy J.; Mirkin, Chad A.; Stegh, Alexander H.] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA. [Hua, Youjia; Peter, Marcus E.] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. [Hua, Youjia; Peter, Marcus E.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Queisser, Markus A.; Sznajder, Jacob I.] Northwestern Univ, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. [Zhang, Hailei; Chin, Lynda] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Zhang, Hailei; Chin, Lynda] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhang, Hailei; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Hailei; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Zhang, Hailei; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. [James, C. David] Northwestern Univ, Feinberg Sch Med, Dept Neurol Surg, Chicago, IL 60611 USA. RP Stegh, AH (reprint author), Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA. EM a-stegh@northwestern.edu RI Mirkin, Chad/E-3911-2010; Day, Emily/A-9026-2012 OI Day, Emily/0000-0002-8707-826X FU Center for Cancer Nanotechnology Excellence (CCNE) initiative of the National Institutes of Health (NIH) [U54 CA151880]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/NIH [R01AR060810, R21AR062898]; Dixon Translational Research Grants Initiative of the Northwestern Memorial Foundation; American Cancer Society; James S. MacDonnell 21st Century Initiative; Coffman Charitable Trust; NIH [P01 CA095616, U01 CA141508, U24 CA143845]; Ben and Catherine Ivy Foundation; NIH National Cancer Institute (NCI) [F32CA171949]; Northwestern University International Institute of Nanotechnology; NCI Cancer Center [P30 CA060553]; Quantitative Bioelemental Imaging Center by NASA Ames Research Center [NNA06CB93G]; Defense Advanced Projects Agency (DARPA) [HR0011-13-2-0018] FX We thank the members of the Stegh laboratory as well as Dr. Kazuo Fushimi and Dr. Paolo Ceppi for constructive discussions and help, and Kurt Harris for his help with the IncuCyte ZOOM instrument. This research was supported by the Center for Cancer Nanotechnology Excellence (CCNE) initiative of the National Institutes of Health (NIH) (U54 CA151880 to C.A.M. and A.H.S.), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/NIH grants (R01AR060810 and R21AR062898 to C.A.M.), the Dixon Translational Research Grants Initiative of the Northwestern Memorial Foundation (to C.A.M. and A.H.S.), a Research Scholar award from the American Cancer Society (to A.H.S.), the James S. MacDonnell 21st Century Initiative, and the Coffman Charitable Trust (to A.H.S.). L.C. was supported by funding from the NIH (P01 CA095616, U01 CA141508, and U24 CA143845) and the Ben and Catherine Ivy Foundation. The research was also supported by the NIH National Cancer Institute (NCI) under award number F32CA171949 to E.S.D. E.S.D. and T.J.M. were supported by the Northwestern University International Institute of Nanotechnology. Core facilities at Northwestern University (i.e., the Center for Advanced Molecular Imaging, the Cellular Imaging Facility, the Developmental Therapeutics Core, and the Mouse Histology and Phenotyping Laboratory) are all supported by NCI Cancer Center Support Grant P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, and the Quantitative Bioelemental Imaging Center is supported by NASA Ames Research Center (NNA06CB93G). This workwas also supported in part by the Defense Advanced Projects Agency (DARPA) Cooperative agreement number HR0011-13-2-0018. NR 57 TC 27 Z9 28 U1 1 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2015 VL 29 IS 7 BP 732 EP 745 DI 10.1101/gad.257394.114 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA CE9KA UT WOS:000352161600006 PM 25838542 ER PT J AU Liang, SH Holland, JP Stephenson, NA Kassenbrock, A Rotstein, BH Daignault, CP Lewis, R Collier, L Hooker, JM Vasdev, N AF Liang, Steven H. Holland, Jason P. Stephenson, Nickeisha A. Kassenbrock, Alina Rotstein, Benjamin H. Daignault, Cory P. Lewis, Rebecca Collier, Lee Hooker, Jacob M. Vasdev, Neil TI PET Neuroimaging Studies of [F-18]CABS13 in a Double Transgenic Mouse Model of Alzheimer's Disease and Nonhuman Primates SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE [F-18]CABS13; metal hypothesis of Alzheimer's disease; rodents; nonhuman primates; transgenic mice; APP/PS1 ID HISTOCHEMICALLY-REACTIVE ZINC; A-BETA; AMYLOID-BETA; PLAQUES; MICE; PROTEIN; COPPER; HYPOTHESIS; BIOMARKER; COGNITION AB Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([F-18] CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the "metal hypothesis of Alzheimer's disease". Herein, a practical radiosynthesis of [F-18] CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [F-18] CABS13 resulted in 19 +/- 5% uncorrected radiochemical yield, relative to starting [F-18]fluoride, with >= 95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/mu mol) within 80 min. Temporal PET neuroimaging studies were carried out in female transgenic B6C3-Tg(APPswe,PSEN 1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7, and 10 months of age. [F-18]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal nonhuman primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable [F-18]-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. C1 [Liang, Steven H.; Stephenson, Nickeisha A.; Kassenbrock, Alina; Rotstein, Benjamin H.; Daignault, Cory P.; Lewis, Rebecca; Collier, Lee; Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.; Stephenson, Nickeisha A.; Kassenbrock, Alina; Rotstein, Benjamin H.; Daignault, Cory P.; Lewis, Rebecca; Collier, Lee; Vasdev, Neil] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Liang, Steven H.; Holland, Jason P.; Stephenson, Nickeisha A.; Rotstein, Benjamin H.; Collier, Lee; Hooker, Jacob M.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Collier, Lee] Advion Inc, Ithaca, NY 14850 USA. [Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu FU Australian National Science and Technology Organisation FX We thank the Australian National Science and Technology Organisation for partial financial support. NR 28 TC 5 Z9 5 U1 6 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD APR PY 2015 VL 6 IS 4 BP 535 EP 541 DI 10.1021/acschemneuro.5b00055 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA CG3MU UT WOS:000353185100005 PM 25776827 ER PT J AU Zhu, CW Scarmeas, N Ornstein, K Albert, M Brandt, J Blacker, D Sano, M Stern, Y AF Zhu, Carolyn W. Scarmeas, Nikolaos Ornstein, Katherine Albert, Marilyn Brandt, Jason Blacker, Deborah Sano, Mary Stern, Yaakov TI Health-care use and cost in dementia caregivers: Longitudinal results from the Predictors Caregiver Study SO Alzheimers & Dementia LA English DT Article DE Caregiving; Medical care; Cost; Dementia; Alzheimer's disease; Longitudinal study ID ALZHEIMERS-DISEASE; HUMAN-SERVICES; FAMILY CAREGIVERS; BEHAVIOR PROBLEMS; PATIENT; INTERVENTION; METAANALYSIS; MULTICENTER; ADAPTATION; MORTALITY AB Objective: To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost. Methods: One hundred forty-seven caregiver/patient dyads were followed annually for 6 years in three academic Alzheimer's disease centers in the United States. Logistic, negative binomial, and generalized linear mixed models were used to examine overall effects of caregiver/patient characteristics on caregivers' hospitalizations, doctor visits, outpatient tests and procedures, and prescription and over-the-counter medications. Results: Patients' comorbid conditions and dependence were associated with increased health-care use and costs of caregivers. Increases in caregiver depressive symptoms are associated with increases in multiple domains of caregivers' health-care use and costs. Discussion: Findings suggest expanding our focus on dementia patients to include family caregivers to obtain a fuller picture of effects of caregiving. Primary care providers should integrate caregivers' needs in health-care planning and delivery. Clinical interventions that treat patients and caregivers as a whole will likely achieve the greatest beneficial effects. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Zhu, Carolyn W.; Ornstein, Katherine] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Scarmeas, Nikolaos; Stern, Yaakov] Taub Inst Res Alzheimers Dis & Aging Brain, Cognit Neurosci Div, New York, NY USA. [Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA. [Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Ornstein, Katherine] Mt Sinai Sch Med, Dept Med, Div Gen Internal Med, New York, NY USA. [Albert, Marilyn; Brandt, Jason] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Brandt, Jason] Copper Ridge Inst, Sykesville, MD USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sano, Mary] James J Peters VA Med Ctr, Bronx, NY USA. RP Zhu, CW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. EM carolyn.zhu@mssm.edu OI Brandt, Jason/0000-0001-7381-6244 FU [AG07370]; [RR00645]; [U01AG010483] FX The Predictors Study is supported by federal grants AG07370, RR00645, and U01AG010483. The authors have reported no conflicts of interest. NR 50 TC 6 Z9 6 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD APR PY 2015 VL 11 IS 4 BP 444 EP 454 DI 10.1016/j.jalz.2013.12.018 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CG6SD UT WOS:000353431800007 PM 24637299 ER PT J AU Ana, EJS Prisciandaro, JJ Saladin, ME McRae-Clark, AL Shaftman, SR Nietert, PJ Brady, KT AF Ana, Elizabeth J. Santa Prisciandaro, James J. Saladin, Michael E. McRae-Clark, Aimee L. Shaftman, Stephanie R. Nietert, Paul J. Brady, Kathleen T. TI D-Cycloserine Combined With Cue Exposure Therapy Fails to Attenuate Subjective and Physiological Craving in Cocaine Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID CONDITIONED PLACE PREFERENCE; EXTINCTION; INDIVIDUALS; DISORDER; RECEPTOR; FEAR AB Background: Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. Methods: In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. Results: DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. Conclusions: 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. Scientific Significance: Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity. C1 [Ana, Elizabeth J. Santa; Prisciandaro, James J.; McRae-Clark, Aimee L.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Clin Neurosci, Charleston, SC 29401 USA. [Ana, Elizabeth J. Santa] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29401 USA. [Shaftman, Stephanie R.; Nietert, Paul J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29401 USA. RP Ana, EJS (reprint author), Med Univ S Carolina, Dept Psychiat, Clin Neurosci Div, 109 Bee St, Charleston, SC 29401 USA. EM santaana@musc.edu FU National Institutes of Health [1R01DA023188-01A1, 3 R01 DA023188-02S1]; South Carolina Clinical and Translational Institute [UL1TR4000062] FX This study was supported by the National Institutes of Health (Grant Nos. 1R01DA023188-01A1 and 3 R01 DA023188-02S1) and the South Carolina Clinical and Translational Institute, UL1TR4000062. NR 43 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD APR PY 2015 VL 24 IS 3 BP 217 EP 224 DI 10.1111/ajad.12191 PG 8 WC Substance Abuse SC Substance Abuse GA CG6MC UT WOS:000353414300007 ER PT J AU Duffy, SA Noonan, D Karvonen-Gutierrez, CA Ronis, DL Ewing, LA Waltje, AH Dalack, GW Smith, PM Carmody, TP Hicks, T Hermann, C AF Duffy, Sonia A. Noonan, Devon Karvonen-Gutierrez, Carrie A. Ronis, David L. Ewing, Lee A. Waltje, Andrea H. Dalack, Gregory W. Smith, Patricia M. Carmody, Timothy P. Hicks, Thomas Hermann, Christopher TI Effectiveness of the Tobacco Tactics Program for Psychiatric Inpatient Veterans: An Implementation Study SO ARCHIVES OF PSYCHIATRIC NURSING LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH-CARE; SMOKING-CESSATION; NICOTINE DEPENDENCE; QUIT SMOKING; MOTIVATION; ADDICTION; ILLNESS; SMOKERS AB Background: The objective of this study was to evaluate the effectiveness of the inpatient, nurse-administered Tobacco Tactics program for patients admitted for psychiatric conditions in two Veterans Affairs (VA) hospitals compared to a control hospital. Methods: This is a subgroup analysis of data from the inpatient tobacco tactics effectiveness trial, which was a longitudinal, pre-post-nonrandomized comparison design with 6-month follow-up in the three large Veterans Integrated Service Networks (VISN) 11 hospitals. Results: Six-month self-reported quit rates for patients admitted for psychiatric conditions increased from 3.5% pre-intervention to 10.2% post-intervention compared to a decrease in self-reported quit rates in the control hospital (12% pre-intervention to 1.6% post-intervention). There was significant improvement in self-reported quit rates for the pre-versus post-intervention time periods in the Detroit and Ann Arbor intervention sites compared to the Indianapolis control site (P = 0.01) and cotinine results were in the same direction. Conclusion: The implementation of the Tobacco Tactics intervention has the potential to significantly decrease smoking and smoking-related morbidity and mortality among smokers admitted to VA hospitals for psychiatric disorders. Published by Elsevier Inc. C1 [Duffy, Sonia A.; Karvonen-Gutierrez, Carrie A.; Ewing, Lee A.] Ann Arbor VA Ctr Clin Management Res Hlth Serv Re, Ann Arbor, MI USA. [Duffy, Sonia A.] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Ronis, David L.; Waltje, Andrea H.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Duffy, Sonia A.; Dalack, Gregory W.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Noonan, Devon] Duke Univ, Sch Nursing, Durham, NC USA. [Smith, Patricia M.] Northern Ontario Sch Med, Thunder Bay, ON, Canada. [Carmody, Timothy P.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hicks, Thomas] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Hermann, Christopher] John D Dingell VA Med Ctr, Detroit, MI USA. RP Duffy, SA (reprint author), 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM bump@umich.edu FU Department of Veterans Affairs Service Directed Project [SDP 06-003] FX First and foremost, the authors would like to express our heartfelt appreciation to the Ann Arbor and Detroit nurses and other staff who included the intervention in their already busy work schedules. The study could not have been accomplished without the hard work of our research partners (Pamela Reeves, Petra Flanagan, Richard White, and Stacey Breedveld), research nurses (Amanda Fore, Judy Heath, and Carmelite Dalmacy), and research assistants (Wanda Hines and Elizabeth Jones). Most importantly, we would like to thank the Veterans that participated in this study. Funding was supported by the Department of Veterans Affairs Service Directed Project (SDP 06-003). NR 28 TC 0 Z9 0 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9417 EI 1532-8228 J9 ARCH PSYCHIAT NURS JI Arch. Psychiatr. Nurs. PD APR PY 2015 VL 29 IS 2 BP 120 EP 126 DI 10.1016/j.apnu.2014.12.002 PG 7 WC Nursing; Psychiatry SC Nursing; Psychiatry GA CG5WR UT WOS:000353367100009 PM 25858205 ER PT J AU Kuhlthau, KA Warfield, ME Hurson, J Delahaye, J Crossman, MK AF Kuhlthau, Karen A. Warfield, Marji E. Hurson, Jill Delahaye, Jennifer Crossman, Morgan K. TI Pediatric provider's perspectives on the transition to adult health care for youth with autism spectrum disorder: Current strategies and promising new directions SO AUTISM LA English DT Article DE autism; transition; youth; health care; pediatrics ID ADOLESCENT MEDICINE; POSITION PAPER; UNITED-STATES; YOUNG-PEOPLE; CHILDREN; NEEDS; DISABILITIES; SOCIETY AB Few youth with autism spectrum disorder (ASD) nationally report receiving services to help them transition from the pediatric health care system to the adult health care system. For example, only one-fifth (21.1%) of youth with ASD receive any transition planning services. To better understand why the transition from pediatric to adult health care is so difficult, we interviewed pediatric health care providers with extensive experience serving youth with ASD. We gathered information about the strategies and interventions they use to transition their patients with ASD to an adult provider. Five interventions or strategies are currently being used. These include providing families with written medical summaries to give to adult providers, compiling lists of available adult providers or community resources, coordinating care and communication between individual pediatric and adult providers, making transition-specific appointments, and using checklists to track transition progress. Other interventions or strategies were identified as needed but not currently in practice, and these focused on education and training. For example, informational workshops were suggested to train families and youth about transition. Training adult providers and medical students was also seen as important. Several respondents additionally identified the need for a transition center where all services could be coordinated in one place. With large numbers of youth with ASD becoming young adults, it seems that pediatric practices might want to consider some of the activities described here. Some of these activities, such as family educational seminars and written medical summaries, are likely relatively easy for a practice to implement. C1 [Kuhlthau, Karen A.; Hurson, Jill; Delahaye, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kuhlthau, Karen A.; Hurson, Jill; Delahaye, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Warfield, Marji E.; Crossman, Morgan K.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02254 USA. RP Kuhlthau, KA (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [R40 MC 19925] FX Transition to Adult Health Care for Youth with Autism Spectrum Disorders," is funded by grant #R40 MC 19925, through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program. NR 36 TC 5 Z9 5 U1 1 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD APR PY 2015 VL 19 IS 3 BP 262 EP 271 DI 10.1177/1362361313518125 PG 10 WC Psychology, Developmental SC Psychology GA CG1IH UT WOS:000353025800002 PM 24497626 ER PT J AU Dearden, C Brown, JR Hillmen, P O'Brien, S Barrientos, JC Reddy, NM Coutre, S Tam, CS Mulligan, S Jaeger, U Barr, PM Furman, RR Kipps, TJ Cymbalista, F Caligaris-Cappio, F Delgado, J Montillo, M DeVos, S Moreno, C Pagel, J Burger, J Chung, D Lin, J Gau, L Chang, B James, D Byrd, J Thornton, P AF Dearden, C. Brown, J. R. Hillmen, P. O'Brien, S. Barrientos, J. C. Reddy, N. M. Coutre, S. Tam, C. S. Mulligan, S. Jaeger, U. Barr, P. M. Furman, R. R. Kipps, T. J. Cymbalista, F. Caligaris-Cappio, F. Delgado, J. Montillo, M. DeVos, S. Moreno, C. Pagel, J. Burger, J. Chung, D. Lin, J. Gau, L. Chang, B. James, D. Byrd, J. Thornton, P. TI Updated efficacy including subgroup analyses and safety in the phase 3 RESONATE (TM) trial of ibrutinib versus ofatumumab in previously treated chronic lymphocytic leukaemia/small lymphocytic lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 20-22, 2015 CL Edinburgh, SCOTLAND SP British Soc Haematol C1 [Dearden, C.] Royal Marsden Hosp, London SW3 6JJ, England. [Brown, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hillmen, P.] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [O'Brien, S.; Burger, J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Barrientos, J. C.] North Shore LIJ Canc Inst, Lake Success, NY USA. [Reddy, N. M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Coutre, S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Tam, C. S.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, C. S.] St Vincents Hosp, Melbourne, Vic, Australia. [Mulligan, S.] Royal N Shore Hosp, Sydney, NSW, Australia. [Jaeger, U.] Med Univ Vienna, Vienna, Austria. [Barr, P. M.] Univ Rochester, Ctr Canc, Rochester, NY USA. [Furman, R. R.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Kipps, T. J.] UCSD Moores Canc Ctr, San Diego, CA USA. [Cymbalista, F.] Hop Avicenne, Paris, France. [Caligaris-Cappio, F.] Univ Vita Salute San Raffaele, Milan, Italy. [Delgado, J.] Hosp Clin Barcelona, Barcelona, Spain. [Montillo, M.] Osped Niguarda Ca Granda, Milan, Italy. [DeVos, S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moreno, C.] Hosp Santa Creu St Pau, Barcelona, Spain. [Pagel, J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chung, D.; Lin, J.; Gau, L.; Chang, B.; James, D.] PharmacyclicsInc, Sunnyvale, CA USA. [Byrd, J.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Thornton, P.] Beaumont Hosp, Dublin 9, Ireland. RI Delgado, Julio/D-4891-2013 OI Delgado, Julio/0000-0002-5157-4376 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2015 VL 169 SU 1 SI SI MA 35 BP 19 EP 20 PG 2 WC Hematology SC Hematology GA CG4CZ UT WOS:000353231200036 ER PT J AU Munir, T Barrientos, JC O'Brien, S Brown, JR Kay, NE Reddy, NM Coutre, S Tam, C Mulligan, S Jaeger, U Devereux, S Pocock, C Robak, T Schuster, SJ Schuh, A Gill, D Bloor, A Dearden, C Moreno, C Cull, G Hamblin, M Jones, JA Kierschniak, T Eckert, K Suzuki, S Hsu, E James, D Byrd, JC Hillmen, P AF Munir, T. Barrientos, J. C. O'Brien, S. Brown, J. R. Kay, N. E. Reddy, N. M. Coutre, S. Tam, C. Mulligan, S. Jaeger, U. Devereux, S. Pocock, C. Robak, T. Schuster, S. J. Schuh, A. Gill, D. Bloor, A. Dearden, C. Moreno, C. Cull, G. Hamblin, M. Jones, J. A. Kierschniak, T. Eckert, K. Suzuki, S. Hsu, E. James, D. Byrd, J. C. Hillmen, P. TI Haematologic and immunologic function and patient-reported outcomes for the phase 3 RESONATE (TM) study of ibrutinib versus ofatumumab in relapsed/refractory chronic lymphocytic leukaemia/small lymphocytic lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 20-22, 2015 CL Edinburgh, SCOTLAND SP British Soc Haematol C1 [Munir, T.; Hillmen, P.] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [Barrientos, J. C.] North Shore LIJ Canc Inst, Lake Success, NY USA. [O'Brien, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Brown, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kay, N. E.] Mayo Clin, Rochester, MN USA. [Reddy, N. M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Coutre, S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Tam, C.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, C.] St Vincents Hosp, Melbourne, Vic, Australia. [Mulligan, S.] Royal N Shore Hosp, Sydney, NSW, Australia. [Jaeger, U.] Med Univ Vienna, Vienna, Austria. [Devereux, S.] NHS Fdn Trust, Kings Coll Hosp, London, England. [Pocock, C.] East Kent Hosp, Canterbury, Kent, England. [Robak, T.] Med Univ Lodz, Lodz, Poland. [Schuster, S. J.] Perelman Ctr Adv Med, Philadelphia, PA USA. [Schuh, A.] Univ Oxford, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford, England. [Gill, D.] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Bloor, A.] Christie Clin, Manchester, Lancs, England. [Dearden, C.] Royal Marsden Hosp, London SW3 6JJ, England. [Moreno, C.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Cull, G.] Sir Charles Gairdner Hosp, Perth, WA, Australia. [Hamblin, M.] Colchester Gen Hosp, Colchester, Essex, England. [Jones, J. A.; Byrd, J. C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Kierschniak, T.; Eckert, K.; Suzuki, S.; Hsu, E.; James, D.] Pharmacyclics Inc, Sunnyvale, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2015 VL 169 SU 1 SI SI MA 170 BP 70 EP 70 PG 1 WC Hematology SC Hematology GA CG4CZ UT WOS:000353231200171 ER PT J AU Munir, T O'Brien, S Jones, JA Coutre, SE Mato, AR Hillmen, P Tam, C Osterborg, A Siddiqi, T Thirman, MJ Furman, RR Ilhan, O Keating, M Call, TG Brown, JR Stevens-Brogan, M Li, Y Clow, F James, D Chu, A Hallek, M Stilgenbauer, S AF Munir, T. O'Brien, S. Jones, J. A. Coutre, S. E. Mato, A. R. Hillmen, P. Tam, C. Osterborg, A. Siddiqi, T. Thirman, M. J. Furman, R. R. Ilhan, O. Keating, M. Call, T. G. Brown, J. R. Stevens-Brogan, M. Li, Y. Clow, F. James, D. Chu, A. Hallek, M. Stilgenbauer, S. TI Results from the phase 2 RESONATE (TM)-17 Trial: Efficacy and safety of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic leukaemia with 17p deletion SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 20-22, 2015 CL Edinburgh, SCOTLAND SP British Soc Haematol C1 [Munir, T.; Hillmen, P.; Keating, M.] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [O'Brien, S.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Jones, J. A.] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Coutre, S. E.] Stanford Univ, Sch Med, Div Hematol, Stanford Canc Ctr, Stanford, CA 94305 USA. [Mato, A. R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Tam, C.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Osterborg, A.] Karolinska Univ, Hosp Solna, Dept Hematol, Solna, Sweden. [Siddiqi, T.] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. [Thirman, M. J.] Univ Chicago Med, Sect Hematol Oncol, Chicago, IL USA. [Furman, R. R.] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA. [Ilhan, O.] Ankara Univ, Fac Med, TR-06100 Ankara, Turkey. [Call, T. G.] Mayo Clin, Div Hematol, Rochester, MN USA. [Brown, J. R.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Stevens-Brogan, M.; Li, Y.; Clow, F.; James, D.; Chu, A.] Pharmacyclics Inc, Sunnyvale, CA USA. [Hallek, M.] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany. [Hallek, M.] Univ Hosp Cologne, Ctr Integrated Oncol Cologne Bonn, Cologne, Germany. [Stilgenbauer, S.] Univ Ulm, D-89069 Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2015 VL 169 SU 1 SI SI MA 172 BP 71 EP 71 PG 1 WC Hematology SC Hematology GA CG4CZ UT WOS:000353231200173 ER PT J AU Pyzer, AR Rajabi, H Stroopinsky, D Rosenblatt, J Palmer, K Coll, M Nahas, M Bar-Natan, M Karp, R Somaiya, P Luptakova, K Jain, S McMasters, M Levine, J Arnason, J Kufe, D Avigan, D AF Pyzer, A. R. Rajabi, H. Stroopinsky, D. Rosenblatt, J. Palmer, K. Coll, M. Nahas, M. Bar-Natan, M. Karp, R. Somaiya, P. Luptakova, K. Jain, S. McMasters, M. Levine, J. Arnason, J. Kufe, D. Avigan, D. TI MUC1 suppresses MiR34a expression leading to an expansion of myeloid-derived suppressor cells (MDSCs) in acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 20-22, 2015 CL Edinburgh, SCOTLAND SP British Soc Haematol C1 [Pyzer, A. R.; Stroopinsky, D.; Rosenblatt, J.; Palmer, K.; Coll, M.; Nahas, M.; Bar-Natan, M.; Karp, R.; Somaiya, P.; Luptakova, K.; Jain, S.; McMasters, M.; Levine, J.; Arnason, J.; Avigan, D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Hematol,Oncol, Boston, MA 02215 USA. [Rajabi, H.; Kufe, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2015 VL 169 SU 1 SI SI MA 211 BP 86 EP 86 PG 1 WC Hematology SC Hematology GA CG4CZ UT WOS:000353231200212 ER PT J AU Dussault, C Toeg, H Nathan, M Wang, ZJ Roux, JF Secemsky, E AF Dussault, Charles Toeg, Hadi Nathan, Meena Wang, Zhi Jian Roux, Jean-Francois Secemsky, Eric TI Electrocardiographic Monitoring for Detecting Atrial Fibrillation After Ischemic Stroke or Transient Ischemic Attack Systematic Review and Meta-Analysis SO Circulation-Arrhythmia and Electrophysiology LA English DT Review DE atrial fibrillation; electrocardiography; meta-analysis; stroke ID HEALTH-CARE PROFESSIONALS; CRYPTOGENIC STROKE; CEREBRAL-ISCHEMIA; PREMATURE BEATS; HOLTER MONITOR; SINUS RHYTHM; ECG; PREVENTION; POPULATION; COHORT AB Background-Atrial fibrillation (AF) is a major cause of stroke. Although standard investigations after an event include electrocardiographic monitoring, the optimal duration to detect AF is unclear. We performed a systematic review and meta-analysis to determine whether the duration of electrocardiographic monitoring after an ischemic event is related to the detection of AF. Methods and Results-Prospective studies that reported the proportion of new AF diagnosed using electrocardiographic monitoring for >12 hours in patients with recent stroke or transient ischemic attack were analyzed. Studies were excluded if the stroke was hemorrhagic or AF was previously diagnosed. A total of 31 articles met inclusion criteria. Longer duration of monitoring was associated with an increased detection of AF when examining monitoring time as a continuous variable (P<0.001 for metaregression analysis). When dichotomizing studies based on monitoring duration, studies with monitoring lasting <= 72 hours detected AF in 5.1%, whereas monitoring lasting >= 7 days detected AF in 15%. The proportion of new diagnosis increased to 29.15% with extended monitoring for 3 months. Significant heterogeneity within studies was detected for both groups (<= 72 hours, I-2=91.3%; >= 7 days, I-2=75.8). When assessing the odds of AF detection in the 3 randomized controlled trial, there was a 7.26 increased odds of AF with long-term monitoring (95% confidence intervals [3.99-12.83]; P value <0.001). Conclusions-Longer duration of electrocardiographic monitoring after cryptogenic stroke is associated with a greater detection of AF. Future investigation is needed to determine the optimal duration of long-term monitoring. C1 [Dussault, Charles; Roux, Jean-Francois] Univ Sherbrooke, Dept Med, Div Cardiac Electrophysiol, Quebec City, PQ, Canada. [Toeg, Hadi] Univ Ottawa, Inst Heart, Dept Surg, Div Cardiac Surg, Ottawa, ON K1N 6N5, Canada. [Nathan, Meena] Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA USA. [Wang, Zhi Jian] Capital Med Univ, Dept Surg, Anzhen Hosp, Div Cardiac Surg, Beijing, Peoples R China. [Secemsky, Eric] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Dussault, C (reprint author), Sherbrooke Univ Hosp, 3001 12e Ave Nord, Sherbrooke, PQ J1L 0G2, Canada. EM charles.dussault@usherbrooke.ca NR 88 TC 15 Z9 16 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2015 VL 8 IS 2 BP 263 EP U42 DI 10.1161/CIRCEP.114.002521 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5CQ UT WOS:000353309100006 PM 25639643 ER PT J AU Shoemaker, MB Bollmann, A Lubitz, SA Ueberham, L Saini, H Montgomery, J Edwards, T Yoneda, Z Sinner, MF Arya, A Sommer, P Delaney, J Goyal, SK Saavedra, P Kanagasundram, A Whalen, SP Roden, DM Hindricks, G Ellis, CR Ellinor, PT Darbar, D Husser, D AF Shoemaker, M. Benjamin Bollmann, Andreas Lubitz, Steven A. Ueberham, Laura Saini, Harsimran Montgomery, Jay Edwards, Todd Yoneda, Zachary Sinner, Moritz F. Arya, Arash Sommer, Philipp Delaney, Jessica Goyal, Sandeep K. Saavedra, Pablo Kanagasundram, Arvindh Whalen, S. Patrick Roden, Dan M. Hindricks, Gerhard Ellis, Christopher R. Ellinor, Patrick T. Darbar, Dawood Husser, Daniela TI Common Genetic Variants and Response to Atrial Fibrillation Ablation SO Circulation-Arrhythmia and Electrophysiology LA English DT Article DE ablation techniques; atrial fibrillation; genomics ID CHROMOSOME 4Q25; CATHETER; RISK; ASSOCIATION; RECURRENCE; PITX2; TRIAL AB Background-Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results-Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio, 1.3 [95% confidence intervals, 1.1-1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions-Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF. C1 [Shoemaker, M. Benjamin; Montgomery, Jay; Edwards, Todd; Yoneda, Zachary; Delaney, Jessica; Goyal, Sandeep K.; Saavedra, Pablo; Kanagasundram, Arvindh; Whalen, S. Patrick; Roden, Dan M.; Ellis, Christopher R.; Darbar, Dawood] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Bollmann, Andreas; Ueberham, Laura; Arya, Arash; Sommer, Philipp; Hindricks, Gerhard; Husser, Daniela] Heart Ctr Leipzig, Dept Electrophysiol, Leipzig, Germany. [Lubitz, Steven A.; Saini, Harsimran; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Saini, Harsimran; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Sinner, Moritz F.] Univ Hosp Munich, Dept Med, Munich, Germany. RP Shoemaker, MB (reprint author), Vanderbilt Univ, Med Ctr, 383 Preston Res Bldg,2220 Pierce Ave, Nashville, TN 37232 USA. EM moore.b.shoemaker@vanderbilt.edu OI Darbar, Dawood/0000-0002-4103-5977 FU American Heart Association [11CRP7420009, EIA 0940116 N, 13EIA14220013]; National Institutes of Health [HL092217, U19 HL65962, UL1 RR024975, R01HL092577, R01HL104156, K24HL105780, K23HL114724]; Clinical and Translational Science Award from the National Center for Advancing Translational Sciences [UL1TR000445]; Volkswagen Foundation [84 901]; German Cardiac Society; National Institutes of Health; Doris Duke Charitable Foundation [2014105] FX At Vanderbilt, this work was supported by grants from the American Heart Association to Dr Shoemaker (11CRP7420009), Dr Darbar (EIA 0940116 N), and grants from the National Institutes of Health to Dr Darbar (HL092217), and Dr Roden (U19 HL65962, and UL1 RR024975). This project was also supported by a Clinical and Translational Science Award (UL1TR000445) from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. At Heart Center Leipzig this work was supported by grants from the Volkswagen Foundation to Dr Husser (#84 901) and the German Cardiac Society to L. Ueberham. At Massachusetts General Hospital this work was supported by National Institutes of Health grants R01HL092577, R01HL104156, and K24HL105780 to Dr Ellinor, and K23HL114724 to Dr Lubitz, an American Heart Association Established Investigator Award 13EIA14220013 to Dr Ellinor, and a Doris Duke Charitable Foundation Clinical Scientist Development Award (2014105) to Dr Lubitz. NR 16 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2015 VL 8 IS 2 BP 296 EP 302 DI 10.1161/CIRCEP.114.001909 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5CQ UT WOS:000353309100010 PM 25684755 ER PT J AU Chung, MK Holcomb, RG Mittal, S Steinberg, JS Gleva, MJ Mela, T Uslan, DZ Mitchell, K Poole, JE AF Chung, Mina K. Holcomb, Richard G. Mittal, Suneet Steinberg, Jonathan S. Gleva, Marye J. Mela, Theofanie Uslan, Daniel Z. Mitchell, Kevin Poole, Jeanne E. CA REPLACE Investigators TI Response to Letter Regarding "REPLACE DARE (Death After Replacement Evaluation) Score: Determinants of All-Cause Mortality After Implantable Device Replacement Or Upgrade From the REPLACE Registry" SO Circulation-Arrhythmia and Electrophysiology LA English DT Letter C1 [Chung, Mina K.] Cleveland Clin, Cleveland, OH 44195 USA. [Mittal, Suneet; Steinberg, Jonathan S.] Valley Hlth Syst, New York, NY USA. [Gleva, Marye J.] Washington Univ, St Louis, MO USA. [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mela, Theofanie] Harvard Univ, Sch Med, Boston, MA USA. [Uslan, Daniel Z.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. [Mitchell, Kevin] BIOTRONIK, Lake Oswego, OR USA. [Poole, Jeanne E.] Univ Washington, Seattle, WA 98195 USA. RP Chung, MK (reprint author), Cleveland Clin, Cleveland, OH 44195 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2015 VL 8 IS 2 BP 514 EP 515 DI 10.1161/CIRCEP.115.002777 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5CQ UT WOS:000353309100039 PM 25900998 ER PT J AU Stitziel, NO Peloso, GM Abifadel, M Cefalu, AB Fouchier, S Motazacker, MM Tada, H Larach, DB Awan, Z Haller, JF Pullinger, CR Varret, M Rabes, JP Noto, D Tarugi, P Kawashiri, M Nohara, A Yamagishi, M Risman, M Deo, R Ruel, I Shendure, J Nickerson, DA Wilson, JG Rich, SS Gupta, N Farlow, DN Neale, BM Daly, MJ Kane, JP Freeman, MW Genest, J Rader, DJ Mabuchi, H Kastelein, JJP Hovingh, GK Averna, MR Gabriel, S Boileau, C Kathiresan, S AF Stitziel, Nathan O. Peloso, Gina M. Abifadel, Marianne Cefalu, Angelo B. Fouchier, Sigrid Motazacker, M. Mahdi Tada, Hayato Larach, Daniel B. Awan, Zuhier Haller, Jorge F. Pullinger, Clive R. Varret, Mathilde Rabes, Jean-Pierre Noto, Davide Tarugi, Patrizia Kawashiri, Masa-aki Nohara, Atsushi Yamagishi, Masakazu Risman, Marjorie Deo, Rahul Ruel, Isabelle Shendure, Jay Nickerson, Deborah A. Wilson, James G. Rich, Stephen S. Gupta, Namrata Farlow, Deborah N. Neale, Benjamin M. Daly, Mark J. Kane, John P. Freeman, Mason W. Genest, Jacques Rader, Daniel J. Mabuchi, Hiroshi Kastelein, John J. P. Hovingh, G. Kees Averna, Maurizio R. Gabriel, Stacey Boileau, Catherine Kathiresan, Sekar CA NHLBI Grand Opportunity Exome TI Exome Sequencing in Suspected Monogenic Dyslipidemias SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE DNA sequencing; exome; genetics; human; lipids ID AUTOSOMAL-DOMINANT HYPERCHOLESTEROLEMIA; APOE P.LEU167DEL MUTATION; FAMILIAL HYPERCHOLESTEROLEMIA; TANGIER-DISEASE; GENE; DISCOVERY; JAPANESE; COMPLEX; DESIGN; UPDATE AB Background-Exome sequencing is a promising tool for gene mapping in Mendelian disorders. We used this technique in an attempt to identify novel genes underlying monogenic dyslipidemias. Methods and Results-We performed exome sequencing on 213 selected family members from 41 kindreds with suspected Mendelian inheritance of extreme levels of low-density lipoprotein cholesterol (after candidate gene sequencing excluded known genetic causes for high low-density lipoprotein cholesterol families) or high-density lipoprotein cholesterol. We used standard analytic approaches to identify candidate variants and also assigned a polygenic score to each individual to account for their burden of common genetic variants known to influence lipid levels. In 9 families, we identified likely pathogenic variants in known lipid genes (ABCA1, APOB, APOE, LDLR, LIPA, and PCSK9); however, we were unable to identify obvious genetic etiologies in the remaining 32 families, despite follow-up analyses. We identified 3 factors that limited novel gene discovery: (1) imperfect sequencing coverage across the exome hid potentially causal variants; (2) large numbers of shared rare alleles within families obfuscated causal variant identification; and (3) individuals from 15% of families carried a significant burden of common lipid-related alleles, suggesting complex inheritance can masquerade as monogenic disease. Conclusions-We identified the genetic basis of disease in 9 of 41 families; however, none of these represented novel gene discoveries. Our results highlight the promise and limitations of exome sequencing as a discovery technique in suspected monogenic dyslipidemias. Considering the confounders identified may inform the design of future exome sequencing studies. C1 [Stitziel, Nathan O.] Washington Univ, Sch Med, Div Cardiovasc, Dept Med, St Louis, MO 63110 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Peloso, Gina M.; Tada, Hayato; Neale, Benjamin M.; Daly, Mark J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Haller, Jorge F.; Freeman, Mason W.] Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. [Haller, Jorge F.; Freeman, Mason W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Peloso, Gina M.; Tada, Hayato; Gupta, Namrata; Farlow, Deborah N.; Neale, Benjamin M.; Daly, Mark J.; Gabriel, Stacey; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Abifadel, Marianne; Varret, Mathilde; Rabes, Jean-Pierre; Boileau, Catherine] INSERM, U698, Paris, France. [Abifadel, Marianne; Varret, Mathilde; Rabes, Jean-Pierre; Boileau, Catherine] Univ Paris Diderot, Paris, France. [Abifadel, Marianne] Univ St Joseph, Lab Biochim, Fac Pharm & Pole Technol Sante, Beirut, Lebanon. [Cefalu, Angelo B.; Noto, Davide; Averna, Maurizio R.] Univ Palermo, Dipartimento Biomed Med Interna & Specialist, Palermo, Italy. [Fouchier, Sigrid; Motazacker, M. Mahdi] Univ Amsterdam, Acad Med Ctr, Dept Expt Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Kastelein, John J. P.; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Larach, Daniel B.; Risman, Marjorie; Rader, Daniel J.] Univ Penn, Dept Med, Perelman Sch Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Awan, Zuhier] King Abdulaziz Univ, Dept Clin Biochem, Jeddah 21413, Saudi Arabia. [Ruel, Isabelle; Genest, Jacques] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. [Haller, Jorge F.; Freeman, Mason W.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pullinger, Clive R.; Deo, Rahul; Kane, John P.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Rabes, Jean-Pierre; Boileau, Catherine] Hop Ambroise Pare, AP HP, Lab Biochim & Genet Mol, Boulogne, France. [Rabes, Jean-Pierre; Boileau, Catherine] Univ Versailles St Quentin en Yvelines, UFR Med Paris Ile de France Ouest, Guyancourt, France. [Tarugi, Patrizia] Univ Modena & Reggio Emilia, Dept Life Sci, Modena, Italy. [Kawashiri, Masa-aki; Yamagishi, Masakazu] Kanazawa Univ, Div Cardiovasc Med, Grad Sch Med, Kanazawa, Ishikawa, Japan. [Nohara, Atsushi; Mabuchi, Hiroshi] Kanazawa Univ, Dept Lipidol, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan. [Shendure, Jay; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan1@partners.org OI Cefalu', Angelo Baldassare/0000-0003-1259-8284; Noto, Davide/0000-0002-5346-2829; Stitziel, Nathan/0000-0002-4963-8211 FU National Heart Lung and Blood Institute (NHLBI) [K08HL114642]; Foundation for Barnes-Jewish Hospital; NHLBI [T32HL007208]; Massachusetts General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan Family Foundation [R01 HL107816]; Fondation Leducq; Lung Cohorts Sequencing Project [HL-102923]; WHI Sequencing Project [HL-102924]; Heart Cohorts Sequencing Project [HL-103010]; Broad Institute Sequencing Project [HL-102925]; Northwest Genomics Center Sequencing Project [HL-102926]; Family Studies Project Team; PHRC [AOM06024]; ANR [ANR-05-PCOD-017, ANR-06-MRAR-038, ANR-08-GENO-002-01]; Conseil de la Recherche de l'Universite Saint-Joseph (Beirut, Lebanon); Lifetime Achievement Award of the Dutch Heart Foundation [2010T082]; NWO [91612122]; Netherlands CardioVascular Research Initiative [CVON2011-19]; European Union [FP7-305707, FP7-603091-2] FX N.O. Stitziel is supported, in part, by a career development award (K08HL114642) from the National Heart Lung and Blood Institute (NHLBI) and also by The Foundation for Barnes-Jewish Hospital. G.M. Peloso is supported by award number T32HL007208 from the NHLBI. S. Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan Family Foundation, R01 HL107816, and a grant from Fondation Leducq. We thank the National Heart, Lung, and Blood Institute GO Exome Sequencing Project (ESP) Family Study Project Team for supporting the exome sequencing. We also thank the ESP component studies, including the Lung Cohorts Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Heart Cohorts Sequencing Project (HL-103010), the Broad Institute Sequencing Project (HL-102925), the Northwest Genomics Center Sequencing Project (HL-102926), and the Family Studies Project Team. This work was also supported by grants from PHRC (AOM06024) and ANR (ANR-05-PCOD-017, ANR-06-MRAR-038, ANR-08-GENO-002-01). M. Abifadel is supported by grants from Conseil de la Recherche de l'Universite Saint-Joseph (Beirut, Lebanon). J.J.P. Kastelein is a recipient of the Lifetime Achievement Award of the Dutch Heart Foundation (2010T082). G.K. Hovingh is a recipient of a NWO Veni grant (project number 91612122), a grant from the Netherlands CardioVascular Research Initiative (CVON2011-19; Genius) and the European Union (Resolve: FP7-305707; TransCard: FP7-603091-2). M. M. Motazacker is supported by a grant from Fondation LeDucq (2009-2014). NR 38 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2015 VL 8 IS 2 BP 343 EP + DI 10.1161/CIRCGENETICS.114.000776 PG 31 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA CG5CV UT WOS:000353309600013 PM 25632026 ER PT J AU Wells, JM Iyer, AS Rahaghi, FN Bhatt, SP Gupta, H Denney, TS Lloyd, SG Dell'Italia, LJ Nath, H Estepar, RSJ Washko, GR Dransfield, MT AF Wells, J. Michael Iyer, Anand S. Rahaghi, Farbod N. Bhatt, Surya P. Gupta, Himanshu Denney, Thomas S. Lloyd, Steven G. Dell'Italia, Louis J. Nath, Hrudaya Estepar, Raul San Jose Washko, George R. Dransfield, Mark T. TI Pulmonary Artery Enlargement Is Associated With Right Ventricular Dysfunction and Loss of Blood Volume in Small Pulmonary Vessels in Chronic Obstructive Pulmonary Disease SO Circulation-Cardiovascular Imaging LA English DT Article DE cardiac magnetic resonance imaging; hypertension, pulmonary; pulmonary disease; pulmonary heart disease; smoking ID CARDIAC MAGNETIC-RESONANCE; EXERCISE PERFORMANCE; COMPUTED-TOMOGRAPHY; LOBE SEGMENTATION; PERCENT EMPHYSEMA; CONTROLLED-TRIAL; SEVERE COPD; HYPERTENSION; LUNG; ECHOCARDIOGRAPHY AB Background-Chronic obstructive pulmonary disease causes significant morbidity and concomitant pulmonary vascular disease and cardiac dysfunction are associated with poor prognosis. Computed tomography-detected relative pulmonary artery (PA) enlargement defined as a PA to ascending aorta diameter ratio >1 (PA:A>1) is a marker for pulmonary hypertension and predicts chronic obstructive pulmonary disease exacerbations. However, little is known about the relationship between the PA: A ratio, pulmonary blood volume, and cardiac function. Methods and Results-A single-center prospective cohort study of patients with chronic obstructive pulmonary disease was conducted. Clinical characteristics and computed tomography metrics, including the PA: A and pulmonary blood vessel volume, were measured. Ventricular functions, volumes, and dimensions were measured by cine cardiac MRI with 3-dimensional analysis. Linear regression examined the relationships between clinical characteristics, computed tomography and cardiac MRI metrics, and 6-minute walk distance. Twenty-four patients were evaluated and those with PA:A>1 had higher right ventricular (RV) end-diastolic and end-systolic volume indices accompanied by lower RV ejection fraction (52 +/- 7% versus 60 +/- 9%; P=0.04). The PA: A correlated inversely with total intraparenchymal pulmonary blood vessel volume and the volume of distal vessels with a cross-sectional area of <5 mm(2). Lower forced expiratory volume, PA:A>1, and hyperinflation correlated with reduced RV ejection fraction. Both PA diameter and reduced RV ejection fraction were independently associated with reduced 6-minute walk distance. Conclusions-The loss of blood volume in distal pulmonary vessels is associated with PA enlargement on computed tomography. Cardiac MRI detects early RV dysfunction and remodeling in nonsevere chronic obstructive pulmonary disease patients with a PA:A>1. Both RV dysfunction and PA enlargement are independently associated with reduced walk distance. C1 [Wells, J. Michael; Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.; Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Wells, J. Michael; Iyer, Anand S.; Bhatt, Surya P.; Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.; Dransfield, Mark T.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Wells, J. Michael; Bhatt, Surya P.; Dransfield, Mark T.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care, Lung Hlth Ctr, Birmingham, AL USA. [Gupta, Himanshu; Lloyd, Steven G.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Nath, Hrudaya] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Rahaghi, Farbod N.; Washko, George R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Estepar, Raul San Jose] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Denney, Thomas S.] Auburn Univ, Dept Elect & Comp Engn, Birmingham, AL USA. RP Wells, JM (reprint author), 1900 Univ Blvd,THT 422, Birmingham, AL 35294 USA. EM jmwells@uab.edu FU Walter B. Frommeyer Jr Fellowship in Investigational Medicine, University of Alabama at Birmingham; National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) [K08HL1123940]; American Heart Association [13CRP16750005]; NIH NHLBI [R01-HL104018, K25 HL104085-04, 1R01HL116931-02, R01HL116473-02, R01HL116473]; NHLBI [U01HL089897, U01HL089856] FX Walter B. Frommeyer Jr Fellowship in Investigational Medicine, University of Alabama at Birmingham and National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) K08HL1123940 (to Dr Wells); American Heart Association 13CRP16750005 (to Dr Bhatt); NIH NHLBI R01-HL104018 (to Dr Gupta); K25 HL104085-04 and 1R01HL116931-02 and R01HL116473-02 (to Dr Estepar); R01HL116473 (to Dr Washko); The COPDGene project is supported by grants from the NHLBI (U01HL089897 and U01HL089856) NR 44 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD APR PY 2015 VL 8 IS 4 AR e002546 DI 10.1161/CIRCIMAGING.114.002546 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG5CX UT WOS:000353309800004 ER PT J AU Grinstein, J Bonaca, MP Jarolim, P Conrad, MJ Bohula-May, E Deenadayalu, N Braunwald, E Giugliano, RP Newby, LK Sabatine, MS Morrow, DA AF Grinstein, Jonathan Bonaca, Marc P. Jarolim, Petr Conrad, Michael J. Bohula-May, Erin Deenadayalu, Naveen Braunwald, Eugene Giugliano, Robert P. Newby, L. Kristin Sabatine, Marc S. Morrow, David A. TI Prognostic Implications of Low Level Cardiac Troponin Elevation Using High-Sensitivity Cardiac Troponin T SO CLINICAL CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; ASSAY; RISK; MORTALITY AB BackgroundHigh-sensitivity cardiac troponin T (hsTnT) is used in many countries, but is not available in the United States. Prior evidence has been viewed as inconclusive as to whether low cardiac troponin T (cTnT) concentrations detected with hsTnT are prognostically meaningful compared with fourth-generation cTnT. HypothesisThe aim of this study was to assess the prognostic performance of low-level cTnT elevations using the hsTnT assay compared with the assay (fourth-generation) currently available in the United States. MethodsWe measured serum cTnT in 4160 patients with non-ST-elevation acute coronary syndrome using both the hsTnT and fourth-generation assays. Patients were stratified at the 99th percentile cut point for each assay. ResultsPatients with baseline hsTnT 14ng/L (n=3697) vs <14ng/L were at higher 30-day risk of cardiovascular death (CVD) or myocardial infarction (MI) (9.1% vs 1.9%, P < 0.0001). After adjusting for all other elements of the Thrombolysis In Myocardial Infarction risk score, hsTnT 14 carried a 5.2-fold higher risk of CVD/MI (95% confidence interval [CI]: 2.6-10.1, P < 0.0001). Low levels of hsTnT (14-50ng/L) also revealed increased risk (CVD/MI: 6.4%, P = 0.002). Importantly, patients with negative fourth-generation cTnT but positive hsTnT were at 4.5-times higher risk of CVD/MI (95% CI: 1.9-11.0, P = 0.0008) than patients with negative hsTnT. In contrast, patients with a negative hsTnT but positive fourth-generation cTnT result had a lower rate of CVD/MI than with a positive hsTnT (1.3% vs 8.2%, P = 0.0005). ConclusionsLow-level increases in cTnT detected using the hsTnT assay identified patients at a meaningfully higher risk and who might otherwise be missed, and improves upon risk stratification using the cTnT assay currently available in the United States. C1 [Bonaca, Marc P.; Bohula-May, Erin; Deenadayalu, Naveen; Braunwald, Eugene; Giugliano, Robert P.; Sabatine, Marc S.; Morrow, David A.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Grinstein, Jonathan; Bonaca, Marc P.; Bohula-May, Erin; Braunwald, Eugene; Giugliano, Robert P.; Sabatine, Marc S.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Jarolim, Petr; Conrad, Michael J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Newby, L. Kristin] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU Abbott; Amgen; AstraZeneca; Beckman Coulter; BG Medicine; BRAHMS; Bristol-Myers Squibb; Buhlmann; Critical Diagnostics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Merck and Co; Nanosphere; Novartis Pharmaceuticals; Ortho-Clinical Diagnostics; Pfizer; Randox; Roche Diagnostics; Sanofi-Aventis; Siemens; Singulex; TIMI Study Group; Daiichi Sankyo; Merck; Roche; National Heart, Lung and Blood Institute of the National Institutes of Health [RC1HL099692, HHSN268201000033C] FX The TIMI Study Group has received research grant support from Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Buhlmann, Critical Diagnostics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Randox, Roche Diagnostics, Sanofi-Aventis, Siemens, and Singulex.; MP Bonaca is an investigator and receives salary support from the TIMI Study Group. He has received remuneration for consulting from Roche.; P Jarolim has received research support from Daiichi Sankyo, Roche Diagnostics, AstraZeneca, Siemens, Abbott, and Merck. He has received remuneration for consulting from T2 Biosystems and Quanterix.; LK Newby has received consulting fees from Roche, see https://www.dcri.org/about-us/conflict-of-interest.; Research reported in this publication was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under award number RC1HL099692 and contract number HHSN268201000033C. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 25 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2015 VL 38 IS 4 BP 230 EP 235 DI 10.1002/clc.22379 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5UO UT WOS:000353361600006 PM 25737394 ER PT J AU Hariharan, P Dudzinski, DM Okechukwu, I Takayesu, JK Chang, YC Kabrhel, C AF Hariharan, Praveen Dudzinski, David M. Okechukwu, Ikenna Takayesu, James Kimo Chang, Yuchiao Kabrhel, Christopher TI Association Between Electrocardiographic Findings, Right Heart Strain, and Short-Term Adverse Clinical Events in Patients With Acute Pulmonary Embolism SO CLINICAL CARDIOLOGY LA English DT Article ID RIGHT-VENTRICULAR DYSFUNCTION; THROMBOEMBOLISM; MANAGEMENT; PROGNOSIS; SEVERITY AB BackgroundElectrocardiographic (ECG) changes may be seen with pulmonary emboli (PE). Whether ECG is associated with short-term adverse clinical events after PE is less well established. HypothesisECG findings are associated with short-term clinical deterioration after PE. MethodsConsecutive adult PE patients were enrolled in an academic emergency department from 2008 to 2011. The primary outcome was right heart strain (RHS) on echocardiogram or CT pulmonary angiography, or TnT 0.1ng/mL. We derived an ECG (TwiST) score that is associated with RHS and short-term adverse clinical events. ResultsWe enrolled 298 patients with PE. On multivariate analysis, T-wave inversion in leads V-1 through V-3 (OR: 4.7, 95% confidence interval [CI]: 1.7-13.2), S wave in lead I (OR: 2.0, 95% CI: 1.1-3.5), and tachycardia (OR: 2.5, 95% CI: 1.3-4.8) were associated with RHS. A TwiST score 2 (n=210, 72%) was 84% (95% CI: 77%-90%) sensitive for the absence of RHS, whereas a TwiST score 5 (n=47, 16%) was 93% (95% CI: 88%-97%) specific for the presence of RHS. ConclusionsA simple ECG (TwiST) score can identify patients likely or not likely to have RHS with >80% specificity and sensitivity and may assist in identifying patients with acute PE at risk for adverse clinical events before pursuing other advanced imaging tests. C1 [Hariharan, Praveen; Okechukwu, Ikenna; Takayesu, James Kimo; Kabrhel, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Vasc Emergencies,Dept Emergency Med, Boston, MA USA. [Dudzinski, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Ctr Vasc Emergencies, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM ckabrhel@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU Harvard Milton Fund FX This study was funded by an award from the Harvard Milton Fund. The funding agency had no influence on the design or conduct of the study and played no role in interpreting the results or drafting the manuscript. NR 22 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2015 VL 38 IS 4 BP 236 EP 242 DI 10.1002/clc.22383 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5UO UT WOS:000353361600007 PM 25847482 ER PT J AU O'Connell, KE Mikkola, AM Stepanek, AM Vernet, A Hall, CD Sun, CC Yildirim, E Staropoli, JF Lee, JT Brown, DE AF O'Connell, Karyn E. Mikkola, Amy M. Stepanek, Aaron M. Vernet, Andyna Hall, Christopher D. Sun, Chia C. Yildirim, Eda Staropoli, John F. Lee, Jeannie T. Brown, Diane E. TI Practical Murine Hematopathology: A Comparative Review and Implications for Research SO COMPARATIVE MEDICINE LA English DT Review ID GENETICALLY-ENGINEERED MICE; HEMATOPOIETIC STEM-CELLS; BONE-MARROW FIBROSIS; MOUSE MODEL; BLOOD COLLECTION; PROPLATELET FORMATION; IRON-DEFICIENCY; ESSENTIAL THROMBOCYTHEMIA; INDUCED IMMUNOSUPPRESSION; THROMBOPOIETIN PRODUCTION AB Hematologic parameters are important markers of disease in human and veterinary medicine. Biomedical research has benefited from mouse models that recapitulate such disease, thus expanding knowledge of pathogenetic mechanisms and investigative therapies that translate across species. Mice in health have many notable hematologic differences from humans and other veterinary species, including smaller erythrocytes, higher percentage of circulating reticulocytes or polychromasia, lower peripheral blood neutrophil and higher peripheral blood and bone marrow lymphocyte percentages, variable leukocyte morphologies, physiologic splenic hematopoiesis and iron storage, and more numerous and shorter-lived erythrocytes and platelets. For accurate and complete hematologic analyses of disease and response to investigative therapeutic interventions, these differences and the unique features of murine hematopathology must be understood. Here we review murine hematology and hematopathology for practical application to translational investigation. C1 [O'Connell, Karyn E.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Comparat Pathol, Southborough, MA USA. [Mikkola, Amy M.; Stepanek, Aaron M.; Vernet, Andyna; Hall, Christopher D.; Brown, Diane E.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Sun, Chia C.] Massachusetts Gen Hosp, Div Nephrol, Program Anemia Signaling Res, Boston, MA 02114 USA. [Sun, Chia C.] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Yildirim, Eda; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Staropoli, John F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Staropoli, John F.; Lee, Jeannie T.; Brown, Diane E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA USA. [Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Brown, DE (reprint author), Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. EM dbrown31@mgh.harvard.edu NR 174 TC 3 Z9 3 U1 3 U2 8 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2015 VL 65 IS 2 BP 96 EP 113 PG 18 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CG6ST UT WOS:000353433400002 PM 25926395 ER PT J AU True, C Alam, SN Cox, K Chan, YM Seminara, SB AF True, Cadence Alam, Sayeda Nasrin Cox, Kimberly Chan, Yee-Ming Seminara, Stephanie B. TI Neurokinin B Is Critical for Normal Timing of Sexual Maturation but Dispensable for Adult Reproductive Function in Female Mice SO ENDOCRINOLOGY LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; REVERSIBLE KALLMANN-SYNDROME; STIMULATES GNRH RELEASE; MONKEY MACACA-MULATTA; ARCUATE NUCLEUS; HORMONE SECRETION; GENE-EXPRESSION; GONADOTROPIN-SECRETION; TESTOSTERONE TREATMENT; TACHYKININ RECEPTORS AB Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of pubertal development than adult reproductive function. NKB receptor-deficient mice are hypogonadotropic but have no defects in the timing of sexual maturation. The current study has performed the first phenotypic evaluation of mice bearing mutations in Tac2, the gene encoding the NKB ligand, to determine whether they have impaired sexual development similar to their human counterparts. Male Tac2(-/-) mice showed no difference in the timing of sexual maturation or fertility compared with wild-type littermates and were fertile. In contrast, Tac2(-/-) females had profound delays in sexual maturation, with time to vaginal opening and first estrus occurring significantly later than controls, and initial abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2(-/-) females were fertile, although they produced fewer pups per litter. Thus, female Tac2(-/-) mice parallel humans harboring NKB pathway mutations, with delayed sexual maturation and activation of the reproductive cascade later in life. Moreover, direct comparison of NKB ligand and receptor-deficient females confirmed that only NKB ligand-deficient animals have delayed sexual maturation, suggesting that in the absence of the NKB receptor, NKB may regulate the timing of sexual maturation through other tachykinin receptors. C1 [True, Cadence; Alam, Sayeda Nasrin; Cox, Kimberly; Chan, Yee-Ming; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [True, Cadence; Alam, Sayeda Nasrin; Cox, Kimberly; Chan, Yee-Ming; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM sseminara@mgh.harvard.edu FU National Institutes of Health [U54 HD028138] FX This work was supported by the National Institutes of Health Grant U54 HD028138. NR 62 TC 9 Z9 9 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2015 VL 156 IS 4 BP 1386 EP 1397 DI 10.1210/en.2014-1862 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG4QX UT WOS:000353272700019 PM 25574869 ER PT J AU Allard, C Desgagne, V Patenaude, J Lacroix, M Guillemette, L Battista, MC Doyon, M Menard, J Ardilouze, JL Perron, P Bouchard, L Hivert, MF AF Allard, C. Desgagne, V. Patenaude, J. Lacroix, M. Guillemette, L. Battista, M. C. Doyon, M. Menard, J. Ardilouze, J. L. Perron, P. Bouchard, L. Hivert, M. F. TI Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns SO EPIGENETICS LA English DT Article DE DNA methylation; fetal programming; gestational diabetes; glycemia; leptin; Mendelian randomization; obesity; pregnancy ID GESTATIONAL DIABETES-MELLITUS; INFLUENCING GLYCEMIC TRAITS; DNA METHYLATION; INTRAUTERINE EXPOSURE; HYPOTHALAMIC NEURONS; PREGNANCY OUTCOMES; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; ASSOCIATION; OBESITY AB Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS(10)) and showed it was an adequate instrumental variable (beta = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 x 10(-11); N = 467). A higher GRS(10) was associated with lower methylation levels at cg12083122 located near LEP (beta = -0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS(10) and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (beta = -0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. C1 [Allard, C.] Univ Sherbrooke, Fac Sci, Dept Math, Sherbrooke, PQ J1K 2R1, Canada. [Desgagne, V.; Bouchard, L.] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Patenaude, J.; Lacroix, M.; Guillemette, L.; Battista, M. C.; Ardilouze, J. L.; Perron, P.; Hivert, M. F.] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Battista, M. C.; Doyon, M.; Menard, J.; Ardilouze, J. L.; Perron, P.; Bouchard, L.; Hivert, M. F.] CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ J1H 5N4, Canada. [Desgagne, V.; Bouchard, L.] CSSS Chicoutimi, Ctr Rech Clin ECOGENE 21, Chicoutimi, PQ, Canada. [Hivert, M. F.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Hivert, M. F.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Univ Sherbrooke, Fac Med & Hlth Sci, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. EM mhivert@partners.org FU Fonds de la recherche du Quebec en sante (FRQ-S); Canadian Institute of Health Research (CIHR); Diabete Quebec grant; Canadian Diabetes Association; Clinical Scientist Award by the Canadian Diabetes Association; Maud Menten Award from the CHIR-Institute of Genetics; FRQ-S; Diabete Quebec internship awards; FRQ-S Master's training awards; CIHR Master's training award; Doctoral training award FX This work was supported by a Fonds de la recherche du Quebec en sante (FRQ-S) operating grant (to M-FH and to PP); a Canadian Institute of Health Research (CIHR) Operating grant (to M-FH); a Diabete Quebec grant (to PP) and a Canadian Diabetes Association operating grant (to J-LA). M-FH was a FRQ-S research scholar and received a Clinical Scientist Award by the Canadian Diabetes Association and the Maud Menten Award from the CHIR-Institute of Genetics. LB is a junior research scholar from the Fonds de la recherche du Quebec en sante (FRQ-S) and a member of the FRQ-S funded Centre de recherche du CHUS. J-LA is a FRQ-S junior 2 research scholar. Analyses were supported by Diabete Quebec internship awards (LG, ML, JP), FRQ-S Master's training awards (to LG, CA and JP), CIHR Master's training award (to CA) and Doctoral training award (to ML). NR 57 TC 19 Z9 19 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PD APR PY 2015 VL 10 IS 4 BP 342 EP 351 DI 10.1080/15592294.2015.1029700 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG2ZE UT WOS:000353144300008 PM 25800063 ER PT J AU Lillis, KP Dulla, C Maheshwari, A Coulter, D Mody, I Heinemann, U Armbruster, M Ziburkus, J AF Lillis, Kyle P. Dulla, Chris Maheshwari, Atul Coulter, Douglas Mody, Istvan Heinemann, Uwe Armbruster, Moritz Ziburkus, Jokubas TI WONOEP appraisal: Molecular and cellular imaging in epilepsy SO EPILEPSIA LA English DT Review DE Imaging; WONOEP; Probes; Microscopy ID GREEN FLUORESCENT PROTEINS; NEURAL ACTIVITY; OPTICAL ELECTROPHYSIOLOGY; CALCIUM INDICATOR; NETWORK DYNAMICS; VOLTAGE SENSOR; RABIES VIRUS; NEURONS; MICROSCOPY; GLUTAMATE AB Great advancements have been made in understanding the basic mechanisms of ictogenesis using single-cell electrophysiology (e.g., patch clamp, sharp electrode), large-scale electrophysiology (e.g., electroencephalography [EEG], field potential recording), and large-scale imaging (magnetic resonance imaging [MRI], positron emission tomography [PET], calcium imaging of acetoxymethyl ester [AM] dye-loaded tissue). Until recently, it has been challenging to study experimentally how population rhythms emerge from cellular activity. Newly developed optical imaging technologies hold promise for bridging this gap by making it possible to simultaneously record the many cellular elements that comprise a neural circuit. Furthermore, easily accessible genetic technologies for targeting expression of fluorescent protein-based indicators make it possible to study, in animal models of epilepsy, epileptogenic changes to neural circuits over long periods. In this review, we summarize some of the latest imaging tools (fluorescent probes, gene delivery methods, and microscopy techniques) that can lead to the advancement of cell- and circuit-level understanding of epilepsy, which in turn may inform and improve development of next generation antiepileptic and antiepileptogenic drugs. C1 [Lillis, Kyle P.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lillis, Kyle P.] Harvard Univ, Sch Med, Boston, MA USA. [Dulla, Chris; Armbruster, Moritz] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Maheshwari, Atul] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Coulter, Douglas] Univ Penn, Sch Med, Dept Pediat Neurol & Neurosci, Philadelphia, PA 19104 USA. [Coulter, Douglas] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Mody, Istvan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol & Physiol, Los Angeles, CA 90095 USA. [Heinemann, Uwe] Charite, Inst Neurophysiol, D-13353 Berlin, Germany. [Ziburkus, Jokubas] Univ Houston, Dept Biol & Biochem, Houston, TX USA. RP Lillis, KP (reprint author), 114 16th St 2600, Charlestown, MA 02129 USA. EM klillis@mgh.harvard.edu OI Ziburkus, Jokubas/0000-0002-1701-4367 FU National Institutes of Health [R01NS074772, R01NS034700]; Caroline Wiess Law Fund for Molecular Medicine FX Dr. Lillis received support from the National Institutes of Health grants R01NS074772 and R01NS034700. Dr. Maheshwari received funding from the Caroline Wiess Law Fund for Molecular Medicine. NR 64 TC 1 Z9 1 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD APR PY 2015 VL 56 IS 4 BP 505 EP 513 DI 10.1111/epi.12939 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CF8LD UT WOS:000352810100005 PM 25779014 ER PT J AU Ni, JQ Zheng, YP Liu, N Wang, X Fang, XT Phukan, R Wood, KB AF Ni, Jianqiang Zheng, Yanping Liu, Ning Wang, Xin Fang, Xiutong Phukan, Rishabh Wood, Kirkham B. TI Radiological evaluation of anterior lumbar fusion using PEEK cages with adjacent vertebral autograft in spinal deformity long fusion surgeries SO EUROPEAN SPINE JOURNAL LA English DT Article DE Adult spine deformity; PEEK cage; Local vertebral autograft; Cage migration ID BONE MORPHOGENETIC PROTEIN-2; STAND-ALONE ANTERIOR; INTERBODY FUSION; FOLLOW-UP; OSTEOGENIC PROTEIN-1; LOCAL AUTOGRAFT; ALLOGRAFT; INSTRUMENTATION; ARTHRODESIS; FEASIBILITY AB The aim of this study was to evaluate the radiographic characteristics of polyetheretherketone (PEEK) cages packed with adjacent vertebral autograft material in lumbar anterior lumbar interbody fusion (ALIF) in spinal deformity long fusion surgeries. This is a retrospective radiographic study. From April 2008 to April 2012, 40 patients (5 males and 35 females, mean age 67 +/- A 9 years) with coronal and/or sagittal spine deformities underwent staged corrective surgery combined with lumbar ALIF using PEEK cages at the L3-L4, L4-L5 or L5-S1 segment with posterior long (a parts per thousand yen4 levels) instrumentation. The mean follow-up time was 27.5 months (13-49 months). We examined the interbody fusion rate and cage subsidence at 3 months postoperatively and final follow-up. Additionally, we evaluated the distance of cage migration at final follow-up and the improvement in lumbar lordosis. The rate of "collapse" of the adjacent vertebra where the autograft was harvested was assessed at the final follow-up. Finally, we examined the cage-related postoperative complications in this series. Solid interbody fusion was achieved in 96.4 % (81/84) of the levels at the final follow-up. A mild forward cage migration was observed, and the mean migration distance at final follow-up was 0.83 mm in L3/4, 0.36 mm in L4/5 and 0.55 mm in L5/S1. There was cage subsidence observed in 8.3 % (7/84) of the levels. In all patients, the PEEK cage maintained a significant increase in segmental lordosis at all postoperative visits. However, a mild reduction in segmental lordosis still occurred with time. The adjacent lumbar vertebral bodies where the autografts were harvested appeared to be intact in height radiologically at the final follow-up. There were no postoperative complications due to bone harvesting or cage insertion. Proximal junctional kyphosis was found in one patient who underwent a subsequent revision surgery. The use of lumbar ALIF with PEEK cages and adjacent vertebral autografts in spinal deformity long fusion surgeries is an effective and safe procedure. The allograft filler is safe and effective in maintaining the shape of harvested vertebrae. Additional long-term follow-up studies are needed to further justify its use. C1 [Ni, Jianqiang; Zheng, Yanping] Shandong Univ, Qilu Hosp, Dept Orthoped, Jinan, Shandong, Peoples R China. [Ni, Jianqiang; Wang, Xin] Yuhuangding Hosp, Dept Orthoped, Yantai, Shandong, Peoples R China. [Ni, Jianqiang; Liu, Ning; Phukan, Rishabh; Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA. [Fang, Xiutong] Affiliated Beijing Capital Med Univ, Beijing Shijitan Hosp, Dept Orthoped, Beijing, Peoples R China. RP Wood, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA. EM KBWOOD@mgh.harvard.edu NR 42 TC 2 Z9 2 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 EI 1432-0932 J9 EUR SPINE J JI Eur. Spine J. PD APR PY 2015 VL 24 IS 4 BP 791 EP 799 DI 10.1007/s00586-014-3745-5 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CF9AL UT WOS:000352853800017 PM 25618451 ER PT J AU Hight, AE Kozin, ED Darrow, K Lehmann, A Boyden, E Brown, MC Lee, DJ AF Hight, Ariel Edward Kozin, Elliott D. Darrow, Keith Lehmann, Ashton Boyden, Edward Brown, M. Christian Lee, Daniel J. TI Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant SO HEARING RESEARCH LA English DT Article ID INFERIOR COLLICULUS; ELECTRICAL-STIMULATION; COCHLEAR IMPLANTS; SPECTRAL RESOLUTION; NEURAL ACTIVITY; OPTICAL CONTROL; CENTRAL NUCLEUS; NERVE; HEARING; NOISE AB Contemporary auditory brainstem implant (ABI) performance is limited by reliance on electrical neurostimulation with its accompanying channel cross talk and current spread to non-auditory neurons. A new generation ABI based on optogenetic technology may ameliorate limitations fundamental to electrical stimulation. The most widely studied opsin is channelrhodopsin-2 (ChR2); however, its relatively slow kinetic properties may prevent the encoding of auditory information at high stimulation rates. In the present study, we compare the temporal resolution of light-evoked responses of ChR2 to a recently developed fast opsin, Chronos, to ChR2 in a murine ABI model. Viral mediated gene transfer via a posterolateral craniotomy was used to express Chronos or ChR2 in the cochlear nucleus (CN). Following a four to eight week incubation period, blue light (473 nm) was delivered via an optical fiber placed directly on the surface of the infected CN, and neural activity was recorded in the contralateral inferior colliculus (IC). Both ChR2 and Chronos evoked sustained responses to all stimuli, even at high pulse rates. In addition, optical stimulation evoked excitatory responses throughout the tonotopic axis of the IC. Synchrony of the light-evoked response to stimulus rates of 14-448 pulses/s was higher in Chronos compared to ChR2 mice (p < 0.05 at 56, 168, and 224 pulses/s). Our results demonstrate that Chronos has the ability to drive the auditory system at higher stimulation rates than ChR2 and may be a more ideal opsin for manipulation of auditory pathways in future optogenetic-based neuroprostheses. (C) 2015 Elsevier B.V. All rights reserved. C1 [Hight, Ariel Edward; Kozin, Elliott D.; Lehmann, Ashton; Brown, M. Christian; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Kozin, Elliott D.; Lehmann, Ashton; Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Hight, Ariel Edward] Harvard Univ, Sch Med, Program Speech & Hearing Biosci & Technol, Boston, MA 02114 USA. [Darrow, Keith] Worcester State Univ, Dept Commun Sci & Disorders, Worcester, MA USA. [Boyden, Edward] MIT, Dept Brain & Cognit Sci, MIT Media Lab, Cambridge, MA 02139 USA. [Boyden, Edward] MIT, Dept Biol Engn, MIT Media Lab, Cambridge, MA 02139 USA. [Boyden, Edward] MIT, McGovern Inst, Cambridge, MA 02139 USA. RP Lee, DJ (reprint author), Harvard Univ, Wilson Auditory Brainstem Implant Program, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Lee@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU Fondation Bertarelli grant; MED-EL grant; National Institutes of Health [DC01089, T32 DC000038, T32 DC000020] FX Preliminary results of this study were presented at the Association for Research in Otolaryngology Midwinter Meeting, February 2013 and 2014. This work was supported by a Fondation Bertarelli grant (DJL and MCB), a MED-EL grant (DJL), and National Institutes of Health Grants DC01089 (MCB), T32 DC000038 (AEH), T32 DC000020 (EDK). NR 44 TC 4 Z9 4 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD APR PY 2015 VL 322 SI SI BP 235 EP 241 DI 10.1016/j.heares.2015.01.004 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA CG2IL UT WOS:000353098000025 PM 25598479 ER PT J AU Tyburczy, ME Jozwiak, S Malinowska, IA Chekaluk, Y Pugh, TJ Wu, CL Nussbaum, RL Seepo, S Dzik, T Kotulska, K Kwiatkowski, DJ AF Tyburczy, Magdalena E. Jozwiak, Sergiusz Malinowska, Izabela A. Chekaluk, Yvonne Pugh, Trevor J. Wu, Chin-Lee Nussbaum, Robert L. Seepo, Sara Dzik, Tomasz Kotulska, Katarzyna Kwiatkowski, David J. TI A shower of second hit events as the cause of multifocal renal cell carcinoma in tuberous sclerosis complex SO HUMAN MOLECULAR GENETICS LA English DT Article ID MALFORMATION-ARTERIOVENOUS MALFORMATION; RASA1 MUTATIONS; TUMORS; GENE; ANGIOMYOLIPOMA; INVOLVEMENT; SUCCINATE; CHILDREN; DISEASE; KIDNEY AB Tuberous sclerosis complex (TSC) is a genetic disorder characterized by seizures and tumor formation in multiple organs, mainly in the brain, skin, kidney, lung and heart. Renal cell carcinoma (RCC) occurs in similar to 3% of TSC patients, and typically develops at age <50. Here we describe genetic findings in two TSC patients with multiple renal tumors, each of whom had the germline mutation TSC2 p.R905Q. The first (female) TSC patient had a left followed by a right nephrectomy at ages 24 and 27. Both kidneys showed multifocal TSC-associated papillary RCC (PRCC). Targeted, next-generation sequencing (NGS) analysis of TSC2 in five tumors (four from the left kidney, one from the right) showed loss of heterozygosity in one tumor, and four different TSC2 point mutations (p.E1351*, p.R1032*, p.R1713H, c.4178_4179delCT) in the other four samples. Only one of the 11 other tumors available from this patient had one of the TSC2 second hit mutations identified. Whole-exome analysis of the five tumors identified a very small number of additional mutated genes, with an average of 3.4 nonsilent coding, somatic mutations per tumor, none of which were seen in >1 tumor. The second (male) TSC patient had bilateral partial nephrectomies (both at age 36), with similar findings of multifocal PRCC. NGS analysis of TSC2 in two of these tumors identified a second hit mutation c.2355 +1G>T in one sample that was not seen in other tumors. In conclusion, we report the first detailed genetic analysis of RCCs in TSC patients. Molecular studies indicate that tumors developed independently due to various second hit events, suggesting that these patients experienced a 'shower' of second hit mutations in TSC2 during kidney development leading to this severe phenotype. C1 [Tyburczy, Magdalena E.; Malinowska, Izabela A.; Chekaluk, Yvonne; Kwiatkowski, David J.] Brigham & Womens Hosp, Div Pulm Med & Genet, Boston, MA 02115 USA. [Jozwiak, Sergiusz; Dzik, Tomasz; Kotulska, Katarzyna] Childrens Mem Hlth Inst Warsaw, Warsaw, Poland. [Pugh, Trevor J.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Pugh, Trevor J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Div Genom Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Div Genom Med, Inst Human Genet, San Francisco, CA 94143 USA. [Seepo, Sara] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, One Blackfan Circle, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu FU NIH [1P01CA120964, 2R37NS031535] FX This work is supported by NIH grants 1P01CA120964 and 2R37NS031535. NR 37 TC 9 Z9 9 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2015 VL 24 IS 7 BP 1836 EP 1842 DI 10.1093/hmg/ddu597 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1WE UT WOS:000353065300003 PM 25432535 ER PT J AU Deruaz, M Luster, AD AF Deruaz, Maud Luster, Andrew D. TI Chemokine-mediated immune responses in the female genital tract mucosa SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; HERPES-SIMPLEX-VIRUS; CD8(+) T-CELLS; CHLAMYDIA-TRACHOMATIS INFECTION; SEXUALLY-TRANSMITTED INFECTIONS; PLASMACYTOID DENDRITIC CELLS; UTERINE EPITHELIAL-CELLS; INNATE LYMPHOID-CELLS; REPRODUCTIVE-TRACT; HIV-1 INFECTION AB The genital tract mucosa is the site where sexually transmitted infections gain entry to the host. The immune response at this site is thus critical to provide innate protection against pathogens that are seen for the very first time as well as provide long-term pathogen-specific immunity, which would be required for an effective vaccine against sexually transmitted infection. A finely regulated immune response is therefore required to provide an effective barrier against pathogens without compromising the capacity of the genital tract to allow for successful conception and fetal development. We review recent developments in our understanding of the immune response in the female genital tract to infectious pathogens, using herpes simplex virus-2, human immunodeficiency virus-1 and Chlamydia trachomatis as examples, with a particular focus on the role of chemokines in orchestrating immune cell migration necessary to achieve effective innate and adaptive immune responses in the female genital tract. C1 [Deruaz, Maud; Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, 149 13th St, Charlestown, MA 02129 USA. EM aluster@mgh.harvard.edu FU National Institutes of Health [P30AI060354, P01AI112521] FX MD and ADL were supported by grants from the National Institutes of Health, P30AI060354 to MD and P01AI112521 to ADL. NR 108 TC 7 Z9 7 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 EI 1440-1711 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD APR PY 2015 VL 93 IS 4 BP 347 EP 354 DI 10.1038/icb.2015.20 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CG5BC UT WOS:000353302900007 PM 25776842 ER PT J AU Cong, J Yang, XQ Zhang, N Shen, J Fan, TP Zhang, Z AF Cong, Juan Yang, Xiaoqian Zhang, Nan Shen, Jacson Fan, Tingpan Zhang, Zhan TI Quantitative analysis of left atrial volume and function during normotensive and preeclamptic pregnancy: a real-time three-dimensional echocardiography study SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Left atrium; Pregnancy; Preeclampsia; Three-dimensional echocardiograph ID ACUTE MYOCARDIAL-INFARCTION; SIZE; TERM; 1ST AB The changes in left atrial (LA) size and function during normotensive and preeclamptic (PE) pregnancy have rarely been previously studied and the results have been inconsistent. The aim of this study was to assess the time changes in LA volume during normal pregnancy, to determine the impact of the increased afterload occurring in PE on maternal LA, and to compare differences in LA geometry and function between early-onset and late-onset PE. Using a real time three-dimensional echocardiograph, the body surface area-indexed LA volume and emptying function (EF) were compared between nonpregnant controls (n = 30), normotensive (n = 43), and PE (36 with early-onset PE and 34 with late-onset PE) pregnant women. During normotensive pregnancy, the indexed LA maximum, pre-contraction, and minimum volumes progressively increased, as well as total, passive, and active EF (P < 0.05, Trimester 3 vs. controls), as an adaption to risen cardiac preload. In the PE group, indexed LA volumes were significantly enlarged and the values of LA EF were markedly decreased (P < 0.05) resulting from elevated ventricular filling pressure and diastolic dysfunction. Compared with late-onset PE, smaller LA volume and greater atrial EF were shown in early-onset PE despite a higher afterload and more hypertrophied ventricle. In conclusion, LA size and function gradually improved to maintain adequate blood volume during normotensive pregnancy, while dilated chamber and reduced action of LA occurred in PE associated with increased afterload. Less LA volume and higher LA EF were shown in early-onset PE than in late-onset PE. C1 [Cong, Juan; Yang, Xiaoqian; Zhang, Nan; Fan, Tingpan; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Zhengzhou 450052, Henan, Peoples R China. [Shen, Jacson] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zhang, Z (reprint author), Zhengzhou Univ, Affiliated Hosp 3, Zhengzhou 450052, Henan, Peoples R China. EM zhangzhanzdsfy@126.com FU Henan Provincial Healthy Scientific and Technological Program [ID_201203048]; Henan Province Medical Academic Technology Leaders of Overseas Training Program [ID_201201055] FX We thank Tianwei Zhao and Songyan Liu for skill training. This work was supported partially by the Henan Provincial Healthy Scientific and Technological Program (Grant ID_201203048) and partially by Henan Province Medical Academic Technology Leaders of Overseas Training Program (Grant ID_201201055). NR 27 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD APR PY 2015 VL 31 IS 4 BP 805 EP 812 DI 10.1007/s10554-015-0628-8 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG4AO UT WOS:000353222400017 PM 25702192 ER PT J AU Infusino, SA Diercks, GR Rogers, DJ Garcia, J Ojha, S Maurer, R Bunting, G Hartnick, CJ AF Infusino, Scott A. Diercks, Gillian R. Rogers, Derek J. Garcia, Jordan Ojha, Shilpa Maurer, Rie Bunting, Glenn Hartnick, Christopher J. TI Establishment of a Normative Cepstral Pediatric Acoustic Database SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; PERTURBATION MEASURES; DYSPHONIA SEVERITY; CONNECTED SPEECH; VOICE FREQUENCY; CHILDREN; CONSISTENCY; PARAMETERS; DISORDERS; INDEX AB IMPORTANCE Few studies have used objective measures to evaluate the development of the normal pediatric voice. Cepstral analysis of continuous speech samples is a reliable method for gathering acoustic data; however, it has not been used to examine the changes that occur with voice development. OBJECTIVE To establish and characterize acoustic patterns of the normal pediatric voice using cepstral analysis of voice samples from a normal pediatric voice database. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 218 children aged 4 to 17 years, for whom English was the primary language spoken at home, conducted at a pediatric otolaryngology practice and pediatric practice in a tertiary hospital (April 2012-May 2014). INTERVENTIONS AND EXPOSURES Sustained vowel utterances and continuous speech samples (4 Consensus Auditory-Perceptual Evaluation of Voice [CAPE-V] and 2 sentences from the rainbow passage) were recorded and analyzed from children with normal voices. MAIN OUTCOMES AND MEASURES Normal values were collected for the acoustic measures studied (ie, fundamental frequency, cepstral peak fundamental frequency, cepstral peak prominence [CPP], low-to-high spectral ratio [L/H ratio], and cepstral-spectral index of dysphonia in recorded phrases) and compiled into a normative acoustic database. RESULTS Significant changes in fundamental frequency were observed with a distinct shift in slope at ages 11 and 14 years in boys for sustained vowel (ages 4-11 years, -6.83 Hz/y [P < .001]; 11-14 years, -27.62 Hz/y [P < .001]; and 14-17 years, -5.68 Hz/y [P = .001]), all voiced (ages 4-11 years, -4.19 Hz/y [P = .002]; 11-14 years, -29.42 Hz/y [P < .001]; and 14-17 years, -4.63 Hz/y [P < .001]), glottal attack (ages 4-11 years, -4.51 Hz/y; 11-14 years, -27.23 Hz/y; and 14-17 years, -1.70 Hz/y [P < .001 for all]), and rainbow(ages < 14 years, -20.68 Hz/y [P < .001]; and 14-17 years, -4.50 Hz/y [P = .001]) recordings. A decreasing linear trend in fundamental frequency among all recordings (vowel, all voiced, easy onset, glottal attack, plosives, and rainbow) was found in girls (-2.56 Hz/y [P < .001], -3.48 Hz/y [P < .001], -2.82 Hz/y [P < .001], -3.49 Hz/y [P < .001], -2.30 Hz/y [P < .001], and -2.98 Hz/y [P = .01], respectively). A linear increase in CPP was seen with age in boys, with significant changes seen in recordings for vowel (0.10 dB/y [P = .05]), all voiced (0.2 dB/y [P < .001]), easy onset (0.13 dB/y [P < .001]), glottal attack (0.12 dB/y [P < .001]), plosives (0.15 dB/y [P < .001]), and rainbow(0.17 dB/y [P = .006]). A significant linear increase in CPP for girls was only seen in all voiced (0.13 dB/y [P < .001]). L/H ratio showed a linear increase with age among all speech samples (vowel, all voiced, easy onset, glottal attack, plosives, and rainbow) in boys (1.14 dB/y [P < .001], 0.92 dB/y [P < .001], 1.19 dB/y [P < .001], 0.79 dB/y [P < .001], 0.69 dB/y [P < .001], and 0.54 dB/y [P = .002], respectively) and girls (0.96 dB/y, 0.60 dB/y, 0.75 dB/y, 0.37 dB/y, 0.44 dB/y, and 0.58 dB/y, respectively [P <= .001 for all]). CONCLUSIONS AND RELEVANCE This represents the first pediatric voice database using frequency-based acoustic measures. Our goal was to characterize the changes that occur in both male and female voices as children age. These findings help illustrate how acoustic measurements change with development and may aid in our understanding of the developing voice, pathologic changes, and response to treatment. C1 [Infusino, Scott A.; Diercks, Gillian R.; Rogers, Derek J.; Garcia, Jordan; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Div Pediat Otolaryngol, Boston, MA 02114 USA. [Ojha, Shilpa] Charing Cross Hosp, London, England. [Maurer, Rie] Brigham & Womens Hosp, Ctr Clin Invest, Boston, MA 02115 USA. [Bunting, Glenn] Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. RP Infusino, SA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Sainfusino@gmail.com NR 27 TC 0 Z9 0 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD APR PY 2015 VL 141 IS 4 BP 358 EP 363 DI 10.1001/jamaoto.2014.3545 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CG3AM UT WOS:000353148800010 PM 25612091 ER PT J AU Sadeh, N Miller, MW Wolf, EJ Harkness, KL AF Sadeh, Naomi Miller, Mark W. Wolf, Erika J. Harkness, Kate L. TI Negative emotionality and disconstraint influence PTSD symptom course via exposure to new major adverse life events SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Stress exposure; Personality; Posttraumatic stress; Longitudinal; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA EXPOSURE; LONGITUDINAL COURSE; PERSONALITY-TRAITS; YOUNG-ADULTS; RISK-FACTORS; NEUROTICISM; DEPRESSION; GENERATION; VETERANS AB Identifying the factors that influence stability and change in chronic posttraumatic stress disorder (PTSD) is important for improving clinical outcomes. Using a cross-lagged design, we analyzed the reciprocal effects of personality and PTSD symptoms over time and their effects on stress exposure in a sample of 222 trauma-exposed veterans (ages 23-68; 90.5% male). Personality functioning and PTSD were measured approximately 4 years apart, and self-reported exposure to major adverse life events during the interim was also assessed. Negative emotionality positively predicted future PTSD symptoms, and this effect was partially mediated by exposure to new events. Constraint (negatively) indirectly affected PTSD via its association with exposure to new events. There were no significant effects of positive emotionality nor did PTSD symptom severity exert influences on personality overtime. Results indicate that high negative affect and disconstraint influence the course of PTSD symptoms by increasing exposure to stressful life events. Published by Elsevier Ltd. C1 [Sadeh, Naomi; Miller, Mark W.; Wolf, Erika J.] Vet Affairs Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Sadeh, Naomi; Miller, Mark W.; Wolf, Erika J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Harkness, Kate L.] Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. RP Sadeh, N (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM Naomi.SamimiSadeh@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435; Sadeh, Naomi/0000-0002-8101-3190 FU VA Merit Review Grant [5I01CX000431-02]; VA Career Development Award FX Funding for this study was provided by a VA Merit Review Grant No. 5I01CX000431-02 awarded to Mark W. Miller as well as a VA Career Development Award to Erika Wolf. Views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of Veterans Affairs. NR 41 TC 4 Z9 4 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2015 VL 31 BP 20 EP 27 DI 10.1016/j.janxdis.2015.01.003 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CG1ZU UT WOS:000353075500003 PM 25659969 ER PT J AU Anderson, M Goldstein, J Morris, L Milano, C Kormos, R Bhama, J Kapur, N Bansal, A Garcia, J Silvestry, S Holman, W O'Neill, W AF Anderson, M. Goldstein, J. Morris, L. Milano, C. Kormos, R. Bhama, J. Kapur, N. Bansal, A. Garcia, J. Silvestry, S. Holman, W. O'Neill, W. TI A Prospective Multicenter Study to Evaluate Safety and Probable Benefit of a Novel Percutaneous Ventricular Assist Device for Right Ventricular: Failure: The RECOVER RIGHT Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Anderson, M.] Einstein Healthcare Network, Cardiothorac Surg, Bryn Mawr, PA USA. [Goldstein, J.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Morris, L.] Einstein Healthcare Network, Bryn Mawr, PA USA. [Milano, C.] Duke Univ, Med Ctr, Durham, NC USA. [Kormos, R.; Bhama, J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Kapur, N.] Tufts Univ, Med Ctr, Boston, MA 02111 USA. [Bansal, A.] Oschner Fdn, New Orleans, LA USA. [Garcia, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Silvestry, S.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Holman, W.] Univ Alabama Birmingham, Birmingham, AL USA. [O'Neill, W.] Henry Ford Hosp, Detroit, MI 48202 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 209 BP S84 EP S84 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500205 ER PT J AU Galie, N Channick, R Chin, K Frey, A Gaine, S Ghofrani, A Hoeper, M Lang, I McLaughlin, V Preiss, R Rubin, LJ Sitbon, O Stefani, M Tapson, V Simonneau, G AF Galie, N. Channick, R. Chin, K. Frey, A. Gaine, S. Ghofrani, A. Hoeper, M. Lang, I. McLaughlin, V. Preiss, R. Rubin, L. J. Sitbon, O. Stefani, M. Tapson, V. Simonneau, G. TI Effect of Selexipag on Morbidity/Mortality in Pulmonary Arterial Hypertension: Results of the GRIPHON Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Galie, N.] Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy. [Channick, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chin, K.] UT Southwestern Med Ctr, Dallas, TX USA. [Frey, A.; Preiss, R.; Stefani, M.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Gaine, S.] Mater Misericordiae Univ Hosp, Dublin, Ireland. [Ghofrani, A.] Univ Giessen, D-35390 Giessen, Germany. [Ghofrani, A.] Marburg Lung Ctr, Marburg, Germany. [Hoeper, M.] Hannover Med Sch, Hannover, Germany. [Hoeper, M.] German Ctr Lung Res, Hannover, Germany. [Lang, I.] Med Univ Vienna, Vienna, Austria. [McLaughlin, V.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Rubin, L. J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Sitbon, O.; Simonneau, G.] Hop Univ Bicetre, Paris, France. [Tapson, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 428 BP S163 EP S163 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500421 ER PT J AU Michel, S LaMuraglia, GM Madariaga, ML Selig, MK Farkash, EA Allan, JS Anderson, LM Madsen, JC AF Michel, S. G. LaMuraglia, G. M., II Madariaga, M. L. Selig, M. K. Farkash, E. A. Allan, J. S. Anderson, L. M. Madsen, J. C. TI Twelve Hour Hypothermic Machine Perfusion for Donor Heart Preservation Leads to Improved Ultrastructural Characteristics Compared to Conventional Cold Storage SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Michel, S. G.] Univ Munich, Cardiac Surg, Munich, Germany. [LaMuraglia, G. M., II; Madariaga, M. L.; Allan, J. S.; Madsen, J. C.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [LaMuraglia, G. M., II; Madariaga, M. L.; Selig, M. K.; Farkash, E. A.; Allan, J. S.; Madsen, J. C.] Harvard Univ, Sch Med, Boston, MA USA. [Selig, M. K.; Farkash, E. A.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Anderson, L. M.] Paragonix Technol, Braintree, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 753 BP S275 EP S275 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500737 ER PT J AU Michel, SG Madariaga, ML LaMuraglia, GM Villani, V Sekijima, M Farkash, EA Colvin, R Allan, JS Yamada, K Sachs, DH Madsen, JC AF Michel, S. G. Madariaga, M. L. LaMuraglia, G. M., II Villani, V. Sekijima, M. Farkash, E. A. Colvin, R. Allan, J. S. Yamada, K. Sachs, D. H. Madsen, J. C. TI The Effects of Kidney Graftectomy on the Tolerance Induced By Heart-Kidney Cotransplantation in Miniature Swine Depends on the MHC Barrier Crossed SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Michel, S. G.] Univ Munich, Cardiac Surg, Munich, Germany. [Madariaga, M. L.; LaMuraglia, G. M., II; Villani, V.; Sekijima, M.; Allan, J. S.; Yamada, K.; Sachs, D. H.; Madsen, J. C.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Madariaga, M. L.; LaMuraglia, G. M., II; Villani, V.; Sekijima, M.; Farkash, E. A.; Colvin, R.; Allan, J. S.; Yamada, K.; Sachs, D. H.; Madsen, J. C.] Harvard Univ, Sch Med, Boston, MA USA. [Farkash, E. A.; Colvin, R.] Massachusetts Gen Hosp, Pathol, 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 381 BP S147 EP S147 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500375 ER PT J AU Moore, C Gao, B Nunez, S Stone, J Addonizio, L Givertz, M Naka, Y Mancini, D Restaino, S Madsen, JC Zorn, E AF Moore, C. Gao, B. Nunez, S. Stone, J. Addonizio, L. Givertz, M. Naka, Y. Mancini, D. Restaino, S. Madsen, J. C. Zorn, E. TI Clonal Composition and Specificity of Graft Infiltrating B Cells in Human Cardiac Allograft Vasculopathy SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Moore, C.; Gao, B.; Nunez, S.; Stone, J.; Madsen, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Addonizio, L.; Naka, Y.; Mancini, D.; Restaino, S.; Zorn, E.] Columbia Univ, Med Ctr, New York, NY USA. [Givertz, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 248 BP S98 EP S98 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500244 ER PT J AU Osho, AA Hirji, SA Gulack, BC Ganapathi, AM Davis, RD Hartwig, MG AF Osho, A. A. Hirji, S. A. Gulack, B. C. Ganapathi, A. M. Davis, R. D. Hartwig, M. G. TI Factors Predicting Survival in Early Lung Retransplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Osho, A. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hirji, S. A.; Gulack, B. C.; Ganapathi, A. M.; Davis, R. D.; Hartwig, M. G.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 681 BP S251 EP S252 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500667 ER PT J AU Tabtabai, S Steiner, J Vaduganathan, M Stone, J Estep, J Witteles, R Giuseppe, F Zucker, M Baran, D Seldin, D Patel, J Hanna, M Cordero-Reyes, A Selby, V Maurer, M Semigran, MJ AF Tabtabai, S. Steiner, J. Vaduganathan, M. Stone, J. Estep, J. Witteles, R. Giuseppe, F. Zucker, M. Baran, D. Seldin, D. Patel, J. Hanna, M. Cordero-Reyes, A. Selby, V. Maurer, M. Semigran, M. J. TI The Use of Circulatory Support While Awaiting Heart Transplant in Patients With AL and TTR: Amyloidosis: A Report From ICCAT, the International Consortium for Cardiac Amyloid Transplant SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Tabtabai, S.; Steiner, J.; Vaduganathan, M.; Stone, J.; Semigran, M. J.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. [Estep, J.; Cordero-Reyes, A.] Houston Methodist Hosp, Cardiol, Houston, TX USA. [Witteles, R.] Stanford Univ, Med Ctr, Cardiol, Stanford, CA 94305 USA. [Giuseppe, F.] Univ Padua, Cardiol, Padua, Italy. [Zucker, M.; Baran, D.] Newark Beth Israel Med Ctr, Cardiol, Newark, NJ USA. [Seldin, D.] Boston Univ, Med Ctr, Hematol, Boston, MA USA. [Patel, J.] Cedars Sinai Med Ctr, Cardiol, Los Angeles, CA USA. [Hanna, M.] Cleveland Clin, Cardiol, Cleveland, OH 44106 USA. [Selby, V.] Univ Calif San Francisco, Cardiol, San Francisco, CA 94143 USA. [Maurer, M.] Columbia Med Ctr, Cardiol, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 241 BP S95 EP S96 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500237 ER PT J AU Vaduganathan, M Tabtabai, S Steiner, JK Stone, JR Estep, JD Witteles, RM Feltrin, G Zucker, MJ Baran, DA Seldin, DC Patel, J Hanna, M Cordero-Reyes, A Selby, V Semigran, MJ Maurer, MS AF Vaduganathan, M. Tabtabai, S. Steiner, J. K. Stone, J. R. Estep, J. D. Witteles, R. M. Feltrin, G. Zucker, M. J. Baran, D. A. Seldin, D. C. Patel, J. Hanna, M. Cordero-Reyes, A. Selby, V. Semigran, M. J. Maurer, M. S. TI Modified BMI Does Not Predict Adverse Outcomes in Patients With Cardiac Amyloid Undergoing Heart Transplantation: A Report From iCCAT (International Consortium for Cardiac Amyloid Transplantation) SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Vaduganathan, M.; Tabtabai, S.; Steiner, J. K.; Stone, J. R.; Semigran, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Estep, J. D.; Cordero-Reyes, A.] Methodist Hosp, Houston, TX 77030 USA. [Witteles, R. M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Feltrin, G.] Univ Padua, Padua, Italy. [Zucker, M. J.; Baran, D. A.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Seldin, D. C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Patel, J.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Hanna, M.] Cleveland Clin, Cleveland, OH 44106 USA. [Selby, V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Maurer, M. S.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 801 BP S292 EP S293 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500784 ER PT J AU Warnecke, G Van Raemdonck, D Smith, M Kukreja, J Loor, G Rea, E Massard, G De Robertis, F Nagendran, J Moradiellos, J Dhital, K Knosalla, C Bermudez, C Tsui, S Garcia, J Wang, I McCurry, K Wagner, F Leseche, G Thomas, P Weigmann, B Tudorache, I Kuhn, C Avsar, M Sommer, W Schiavon, M Santelmo, N Falcoz, P Olland, A Deuse, T Varela, A Simon, A Madsen, J Hertz, M Reichenspurner, H Haverich, A Ardehali, A AF Warnecke, G. Van Raemdonck, D. Smith, M. Kukreja, J. Loor, G. Rea, E. Massard, G. De Robertis, F. Nagendran, J. Moradiellos, J. Dhital, K. Knosalla, C. Bermudez, C. Tsui, S. Garcia, J. Wang, I. McCurry, K. Wagner, F. Leseche, G. Thomas, P. Weigmann, B. Tudorache, I. Kuehn, C. Avsar, M. Sommer, W. Schiavon, M. Santelmo, N. Falcoz, P. Olland, A. Deuse, T. Varela, A. Simon, A. Madsen, J. Hertz, M. Reichenspurner, H. Haverich, A. Ardehali, A. TI The Organ Care System (OCS (TM)) Lung INSPIRE International Trial Results SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 15-18, 2015 CL Nice, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Warnecke, G.; Weigmann, B.; Tudorache, I.; Kuehn, C.; Avsar, M.; Haverich, A.] Hannover Med Sch, Hannover, Germany. [Van Raemdonck, D.] Leuven Univ Hosp, Leuven, Belgium. [Smith, M.] St Josephs Med Ctr, Phoenix, AZ USA. [Kukreja, J.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Loor, G.; Hertz, M.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Rea, E.; Schiavon, M.] Univ Padua Hosp, Padua, Italy. [Massard, G.; Santelmo, N.; Falcoz, P.; Olland, A.] Strasbourg Univ Hosp, Strasbourg, France. [De Robertis, F.; Simon, A.] Harefield Hosp, London, England. [Nagendran, J.] Univ Alberta, Med Ctr, Edmonton, AB, Canada. [Moradiellos, J.; Varela, A.] Univ Puerta de Hierro Hosp, Madrid, Spain. [Dhital, K.] St Vincents Hosp, Sydney, NSW 2010, Australia. [Knosalla, C.] German Heart Inst, Berlin, Germany. [Bermudez, C.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Tsui, S.] Papworth Hosp, Cambridge CB3 8RE, England. [Garcia, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, I.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [McCurry, K.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Wagner, F.; Deuse, T.] Univ Hamburg Hosp, Hamburg, Germany. [Leseche, G.] Hop Xavier Bichat, Paris, France. [Thomas, P.] Univ Hosp Marseille, Marseille, France. [Ardehali, A.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. RI falcoz, pierre-emmanuel/N-1239-2016; Varela de Ugarte, Andres/B-4837-2017 OI Varela de Ugarte, Andres/0000-0001-8827-2454 NR 0 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2015 VL 34 IS 4 SU S MA 242 BP S96 EP S96 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA CG4JN UT WOS:000353251500238 ER PT J AU Koyuncuoglu, CZ Calisir, K Saylan, I Yassibag, Z Metin, S Tuncer, O Kantarci, A AF Koyuncuoglu, Cenker Zeki Calisir, Kerem Saylan, Isil Yassibag, Zeynep Metin, Suleyman Tuncer, Ozen Kantarci, Alpdogan TI Implant-Supported Full-Mouth Restoration in a Young Patient With Generalized Aggressive Periodontitis SO Journal of Oral Implantology LA English DT Article ID OSSEOINTEGRATED IMPLANTS; DIAMETER IMPLANTS; LONG-TERM; THERAPY C1 [Koyuncuoglu, Cenker Zeki] Istanbul Aydin Univ, Dept Periodontol, Fac Dent, Istanbul, Turkey. [Calisir, Kerem] Istanbul Univ, Dept Prosthodont, Fac Dent, Istanbul, Turkey. [Saylan, Isil; Yassibag, Zeynep; Metin, Suleyman; Tuncer, Ozen] Istanbul Univ, Dept Periodontol, Fac Dent, Istanbul, Turkey. [Kantarci, Alpdogan] Ctr Periodontol, Dept Appl Oral Sci, Forsyth Inst, Cambridge, MA USA. RP Koyuncuoglu, CZ (reprint author), Istanbul Aydin Univ, Dept Periodontol, Fac Dent, Istanbul, Turkey. EM cenker.k@gmail.com NR 20 TC 0 Z9 0 U1 1 U2 4 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0160-6972 EI 1548-1336 J9 J ORAL IMPLANTOL JI J. Oral Implant. PD APR PY 2015 VL 41 IS 2 BP 209 EP 213 DI 10.1563/AAID-JOI-D-12-00226 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CG5BD UT WOS:000353303000024 PM 23641670 ER PT J AU Rosen, R Hu, L Amirault, J Khatwa, U Ward, DV Onderdonk, A AF Rosen, Rachel Hu, Lan Amirault, Janine Khatwa, Umakanth Ward, Doyle V. Onderdonk, Andrew TI 16S Community Profiling Identifies Proton Pump Inhibitor Related Differences in Gastric, Lung, and Oropharyngeal Microflora SO JOURNAL OF PEDIATRICS LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; NORTH-AMERICAN-SOCIETY; ACUTE OTITIS-MEDIA; GASTROESOPHAGEAL-REFLUX; PEDIATRIC-GASTROENTEROLOGY; ACQUIRED PNEUMONIA; CYSTIC-FIBROSIS; NONACID REFLUX; CHILDREN; BACTERIAL AB Objectives To test the hypothesis that proton pump inhibitor (PPI) use results in changes in gastric microflora which, through full column reflux, results in lung and oropharyngeal microflora changes. Study design We performed a prospective, cross-sectional cohort study of 116 children (57 off and 59 on PPIs) undergoing simultaneous bronchoscopy and upper endoscopy for the evaluation of chronic cough. We performed 16S sequencing on gastric, bronchoalveolar lavage, and oropharyngeal fluid. Fifty patients also underwent multi-channel intraluminal impedance testing. Results Streptococcus was more abundant in the gastric fluid of patients taking PPIs, and there was a significant correlation with PPI dose (mg/kg/d) and abundance of gastric Streptococcus (P = .01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in patients treated with PPI. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the 2 sites and 2 of the 8 (Lactococcus, Acinetobacter) were more abundant in patients with more full column reflux, suggesting direct aspiration. Principal component analysis revealed greater overlap between gastric and lung than oropharyngeal microflora. Conclusions PPI use was associated with differences in gastric, lung, and oropharyngeal microflora. Although microflora exchange can occur between all 3 sites, gastric and lung microflora are more closely related, and the mechanism of exchange between sites may be aspiration of full column reflux. C1 [Rosen, Rachel; Amirault, Janine] Boston Childrens Hosp, Div Gastroenterol & Nutr, Aerodigest Ctr, Boston, MA 02115 USA. [Hu, Lan] Dana Farber Canc Inst, Ctr Computat Canc Biol, Boston, MA 02115 USA. [Khatwa, Umakanth] Boston Childrens Hosp, Div Pulm Med, Aerodigest Ctr, Boston, MA USA. [Ward, Doyle V.] Broad Inst, Cambridge, MA USA. [Onderdonk, Andrew] Brigham & Womens Hosp, Dept Microbiol, Boston, MA 02115 USA. RP Rosen, R (reprint author), Boston Childrens Hosp, Div Gastroenterol & Nutr, Aerodigest Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM rachel.rosen@childrens.harvard.edu FU National Institutes of Health [K23 DK073713, R03DK089146]; Boston Children's Hospital Translational Research Program Junior Investigator Award FX Supported by the National Institutes of Health (K23 DK073713 and R03DK089146 [to R.R.]) and Boston Children's Hospital Translational Research Program Junior Investigator Award (to R.R.). The authors declare no conflicts of interest. NR 31 TC 13 Z9 13 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2015 VL 166 IS 4 BP 917 EP 923 DI 10.1016/j.jpeds.2014.12.067 PG 7 WC Pediatrics SC Pediatrics GA CG6DL UT WOS:000353385700028 PM 25661411 ER PT J AU Hatch, KM Woodcock, EC Talamo, JH AF Hatch, Kathryn M. Woodcock, Emily C. Talamo, Jonathan H. TI Intraocular Lens Power Selection and Positioning With and Without Intraoperative Aberrometry SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID REFRACTIVE SURGERY; CATARACT-SURGERY; ASTIGMATISM; BIOMETRY; EYES AB PURPOSE: To determine the value of intraoperative aberrometry in cases of toric intraocular lens (IOL) implantation and positioning. METHODS: In this non-randomized retrospective comparative trial, two groups of eyes underwent cataract extraction with toric IOL implantation: the aberrometry group (n = 37 eyes), where toric IOL power and alignment were determined before surgery with automated keratometry, standard optical biometry, and an online calculator and then refined using intraoperative aberrometry, and the toric calculator group (n = 27 eyes), where IOL selection was performed in a similar manner but without intraoperative aberrometry. The primary outcome measure was mean postoperative residual refractive astigmatism (RRA). RESULTS: Mean RRA measured at follow-up after surgery was 0.46 +/- 0.42 and 0.68 +/- 0.34 diopters (D) in the aberrometry and toric calculator groups, respectively (P = .0153). A 75% and 57% reduction in cylinder was noted between preoperative keratometric astigmatism and postoperative RRA in the aberrometry and toric calculator groups, respectively (P = .0027). RRA of 0.25 D or less, 0.50 D or less, 0.75 D or less, and 1.00 D or less was seen 38%, 78%, 86%, and 95% of the time, respectively, in the aberrometry group and 22%, 33%, 74%, and 89% of the time, respectively, in the toric calculator group. These data show that the chance of a patient being in a lower postoperative RRA range increased when intraoperative aberrometry was used (P = .0130). CONCLUSIONS: Patients undergoing cataract extraction with toric IOL placement aided by intraoperative aberrometry were 2.4 times more likely to have less than 0.50 D of RRA compared to standard methods. C1 [Hatch, Kathryn M.; Woodcock, Emily C.; Talamo, Jonathan H.] Massachusetts Eye & Ear Infirm, Waltham, MA 02451 USA. RP Hatch, KM (reprint author), Massachusetts Eye & Ear Infirm, 1601 Trapelo Rd,Suite 184, Waltham, MA 02451 USA. EM kathryn_hatch@meei.harvard.edu NR 15 TC 8 Z9 8 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X EI 1938-2391 J9 J REFRACT SURG JI J. Refractive Surg. PD APR PY 2015 VL 31 IS 4 BP 237 EP 243 DI 10.3928/1081597X-20150319-03 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CG5PQ UT WOS:000353345600004 PM 25884578 ER PT J AU McNeil, JK AF McNeil, Juli K. TI Letter to the Editor for the Special Issue on Military Social Work SO JOURNAL OF SOCIAL WORK EDUCATION LA English DT Letter C1 US Dept Vet Affairs, Vet Integrated Serv Network VISN 17, Washington, DC 20420 USA. RP McNeil, JK (reprint author), US Dept Vet Affairs, Vet Integrated Serv Network VISN 17, Washington, DC 20420 USA. NR 8 TC 0 Z9 0 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1043-7797 EI 2163-5811 J9 J SOC WORK EDUC JI J. Soc. Work Educ. PD APR 1 PY 2015 VL 51 SU 1 SI SI BP S145 EP S148 DI 10.1080/10437797.2015.1001297 PG 4 WC Education & Educational Research; Social Work SC Education & Educational Research; Social Work GA CG7RA UT WOS:000353500900011 ER PT J AU Ersek, M Thorpe, J Kim, H Thomasson, A Smith, D AF Ersek, Mary Thorpe, Joshua Kim, Hyejin Thomasson, Arwin Smith, Dawn TI Exploring End-of-Life Care in Veterans Affairs Community Living Centers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nursing homes; palliative care; end-of-life care; veterans; quality of care ID NURSING-HOME RESIDENTS; FAMILY ASSESSMENT; PALLIATIVE CARE; QUALITY MEASURE; NATIONWIDE; HOSPICE; PERCEPTIONS; TRANSITIONS; PLACE AB ObjectivesTo compare quality of end-of-life (EOL) care indicators and family evaluation of care in community living centers (CLCs) with that of EOL care in acute, intensive, and hospice and palliative care units. DesignRetrospective chart review and survey with next of kin of recently deceased inpatients. SettingInpatient Veterans Affairs (VA) Medical Centers (N=145), including 132 CLCs, across the United States. ParticipantsThe chart review included all individuals who died in VA inpatient units (n=57,397). Family survey results included data for 33,497 veterans. MeasurementsIndicators of optimal EOL care: palliative consultation in the last 90days of life, contact with a chaplain, family contact with a chaplain, and emotional support given to family after death. The main outcome was a single Bereaved Family Survey item in which respondents provided a global evaluation of quality of EOL care (excellent to very good, good, fair to poor). ResultsFamily evaluations of overall EOL care and quality of EOL care indicators for veterans who died in CLCs were better than those of veterans dying in acute or intensive care units but worse than those dying in hospice or palliative care units. ConclusionCare in CLCs can be enhanced through the integration of palliative care practices. Future research should identify critical elements of enhancing EOL care in nursing homes. C1 [Ersek, Mary; Thorpe, Joshua; Thomasson, Arwin; Smith, Dawn] Vet Affairs Med Ctr, Performance Reporting & Outcomes Measurement Impr, Philadelphia, PA USA. [Ersek, Mary; Kim, Hyejin; Smith, Dawn] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Thorpe, Joshua] Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Thorpe, Joshua] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. RP Ersek, M (reprint author), Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave,Annex Suite 203, Philadelphia, PA 19104 USA. EM mary.ersek@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, which had no role in the design, methods, participant recruitment, data collection, analysis, or preparation of manuscript or in the decision to submit the manuscript for publication. All authors had access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. NR 27 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 IS 4 BP 644 EP 650 DI 10.1111/jgs.13348 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CG4EB UT WOS:000353234900003 PM 25809839 ER PT J AU Eng, JA Clough-Gorr, K Cabral, HJ Silliman, RA AF Eng, Jessica A. Clough-Gorr, Kerri Cabral, Howard J. Silliman, Rebecca A. TI Predicting 5-and 10-Year Survival in Older Women with Early-Stage Breast Cancer: Self-Rated Health and Walking Ability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE breast cancer; physical function; self-rated health ID COMPREHENSIVE GERIATRIC ASSESSMENT; SOCIAL SUPPORT SURVEY; PROGNOSTIC-FACTORS; PROSTATE-CANCER; SURVEY SF-36; MORTALITY; FRAILTY; OUTCOMES; ADULTS; MULTICENTER AB ObjectivesTo determine life expectancy for older women with breast cancer. DesignProspective longitudinal study with 10years of follow-up data. SettingHospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). ParticipantsWomen aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N=615; 17% aged 80, 52% Stage I, 58% with 2 comorbidities). MeasurementsBaseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. ResultsAt the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5years, P.001; 0.300 vs 0.648 at 10years, P<.001). There were no differences between the groups in breast cancer-specific survival at 5 and 10years (P = .66 at 5years, P=.16 at 10years). ConclusionThe combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer. C1 [Eng, Jessica A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Eng, Jessica A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Clough-Gorr, Kerri] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Silliman, Rebecca A.] Boston Univ, Sch Med, Sect Geriatr, Boston, MA 02118 USA. [Silliman, Rebecca A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Eng, JA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,181G, San Francisco, CA 94121 USA. EM jessica.eng@ucsf.edu FU National Cancer Institute [R01 CA106979, R01 CA/AG 70818, R01 CA84506]; John A. Hartford Foundation; Department of Veterans Affairs Quality Scholars Program; Boston University Clinical and Translational Science Institute (CTSI); National Institutes for Health [K05 CA92395] FX Data collection for the initial study was supported by the National Cancer Institute (R01 CA106979, R01 CA/AG 70818, R01 CA84506). Dr. Eng was supported by the John A. Hartford Foundation and the Department of Veterans Affairs Quality Scholars Program. Dr. Cabral was supported by the Boston University Clinical and Translational Science Institute (CTSI). Dr. Silliman was supported by the National Institutes for Health (K05 CA92395). NR 30 TC 4 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 IS 4 BP 757 EP 762 DI 10.1111/jgs.13340 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CG4EB UT WOS:000353234900019 PM 25900489 ER PT J AU Kramer, BJ Creekmur, B Cote, S Saliba, D AF Kramer, Betty Jo (Josea) Creekmur, Beth Cote, Sarah Saliba, Debra TI Improving Access to Noninstitutional Long-Term Care for American Indian Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE rural; Department of Veterans Affairs; Indian Health Service ID QUALITY-OF-LIFE; HEALTH-SERVICE; DUAL-USE; MANAGEMENT AB Home-based primary care (HBPC) is an effective model of noninstitutional long-term care developed in the Department of Veterans Affairs (VA) to provide ongoing care to homebound persons. Significant rural populations of American Indians have limited access to services designed for frail older adults. Fourteen Veterans Affairs Medical Centers (VAMCs) initiated efforts to expand access to HBPC in concert with local tribes and Indian Health Service (IHS) facilities. This study characterizes the resulting emerging models of HBPC and co-management. Using an observational design, key respondent telephone interviews (n=37) were conducted with stakeholders representing the 14 VAMCs to describe these HBPC programs, and HBPC models were evaluated in relation to VAMC organizational culture as revealed on the annual VA All Employee Survey. Twelve VAMCs independently developed HBPC expansion programs for American Indian veterans, and six different program models were implemented. Two models were unique to collaborations between VAMCs and tribes; in these collaborations, the tribes retained primary care responsibilities. VAMC used the other four models for delivery of care in remote rural areas to all veteran populations, American Indians and non-Indians alike. Strategies to improve access by reducing geographic barriers occur in all models. Comparing mean VAMC organizational culture ratings, as defined in the Competing Values Framework, revealed significant group differences for one of these six models. Findings from this study illustrate the flexibility of the HBPC program and opportunities for co-management and expansion of healthcare access for American Indians and non-Indians, particularly in rural areas. C1 [Kramer, Betty Jo (Josea); Creekmur, Beth; Cote, Sarah; Saliba, Debra] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Kramer, Betty Jo (Josea); Saliba, Debra] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Los Angeles, CA 90095 USA. [Saliba, Debra] Univ Calif Los Angeles, Jewish Home Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Corp, Santa Monica, CA USA. RP Kramer, BJ (reprint author), Greater Los Angeles Healthcare Syst GRECC, 16111 Plummer St 11E, Sepulveda, CA 91343 USA. EM josea.kramer@va.gov OI Creekmur, Beth/0000-0001-7802-1125 FU VA Health Services Research [RRP 12-434, IIR 12-063]; VA Office of Rural Health through VA Office of Geriatrics and Extended Care FX Project Support: VA Health Services Research RRP 12-434 and IIR 12-063.; We wish to acknowledge the invaluable assistance of Barry Kraus in background research and facilitating key respondent interviews. We also wish to acknowledge that the funding source for the HBPC expansion projects was the VA Office of Rural Health through a proposal from the VA Office of Geriatrics and Extended Care. We would also like to thank the VHA Organizational Assessment Sub-Committee for reviewing the study proposal and granting access to the AES data. The valuable contribution of the National Center for Organization Development staff for collecting and managing these data is also appreciated. We thank the National Center for Organization Development for working with us to determine the appropriate data subset and preparing the data for our research purposes. NR 30 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 IS 4 BP 789 EP 796 DI 10.1111/jgs.13344 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CG4EB UT WOS:000353234900024 PM 25854124 ER PT J AU Chen, P Dowal, S Schmitt, E Habtemariam, D Hshieh, TT Victor, R Boockvar, KS Inouye, SK AF Chen, Pei Dowal, Sarah Schmitt, Eva Habtemariam, Daniel Hshieh, Tammy T. Victor, Ryan Boockvar, Kenneth S. Inouye, Sharon K. TI Hospital Elder Life Program in the Real World: The Many Uses of the Hospital Elder Life Program Website SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Hospital Elder Life Program; delirium prevention; dementia; program dissemination; geriatrics education; web-based training ID PREDICTION RULE; DELIRIUM; INTERVENTIONS; CARE; OUTCOMES; SURGERY; MODEL AB The Hospital Elder Life Program (HELP) can prevent delirium, a common condition in older hospitalized adults associated with substantial morbidity, mortality, and healthcare costs. In 2011, HELP transitioned to a web-based dissemination model to provide accessible resources, including implementation materials; information for healthcare professionals, patients, and families; and a searchable reference database. It was hypothesized that, although intended to assist sites to establish HELP, the resources that the HELP website offer might have broader applications. An e-mail was sent to all HELP website registrants from September 10, 2012, to March 15, 2013, requesting participation in an online survey to examine uses of the resources on the website and to evaluate knowledge diffusion related to these resources. Of 102 responding sites, 73 (72%) completed the survey. Thirty-nine (53%) had implemented and maintained an active HELP model. Twenty-six (35%) sites had used the HELP website resources to plan for implementation of the HELP model and 35 (50%) sites to implement and support the program during and after launch. Sites also used the resources for the development of non-HELP delirium prevention programs and guidelines. Forty-five sites (61%) used the website resources for educational purposes, targeting healthcare professionals, patients, families, or volunteers. The results demonstrated that HELP resources were used for implementation of HELP and other delirium prevention programs and were also disseminated broadly in innovative educational efforts across the professional and lay communities. C1 [Chen, Pei; Boockvar, Kenneth S.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Dowal, Sarah; Schmitt, Eva; Habtemariam, Daniel; Victor, Ryan; Inouye, Sharon K.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Hshieh, Tammy T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Boockvar, Kenneth S.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Inouye, Sharon K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gerontol, Boston, MA 02215 USA. RP Chen, P (reprint author), Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM pei.chen@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU National Institute on Aging [K07AG041835]; Retirement Research Foundation [2013-87]; National Institutes of Health [AG000158]; Fan Fox and Leslie Samuels Foundation; Greenwall Foundation; Mount Sinai Older Americans Independence Center; Milton and Shirley F. Levy Family Chair FX This work was supported in part by Grants K07AG041835 (SKI) from the National Institute on Aging and 2013-87 (SKI) from the Retirement Research Foundation. Dr. Hshieh is supported by the T32 Training Grant AG000158 from the National Institutes of Health. Dr. Boockvar is supported by the Fan Fox and Leslie Samuels Foundation, Greenwall Foundation, and Mount Sinai Older Americans Independence Center. Dr. Inouye is supported by the Milton and Shirley F. Levy Family Chair. NR 30 TC 0 Z9 0 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 IS 4 BP 797 EP 803 DI 10.1111/jgs.13343 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CG4EB UT WOS:000353234900025 PM 25877747 ER PT J AU Lage, DE Rusinak, D Carr, D Grabowski, DC Ackerly, DC AF Lage, Daniel E. Rusinak, Donna Carr, Darcy Grabowski, David C. Ackerly, D. Clay TI Creating a Network of High-Quality Skilled Nursing Facilities: Preliminary Data on the Postacute Care Quality Improvement Experiences of an Accountable Care Organization SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE postacute care; skilled nursing facilities; accountable care organizations ID REDUCE HOSPITALIZATIONS; HOME RESIDENTS; MEDICARE; REHOSPITALIZATION; SAVINGS; IMPACT AB Postacute care (PAC) is an important source of cost growth and variation in the Medicare program and is critical to accountable care organization (ACO) and bundled payment efforts to improve quality and value in the Medicare program, but ACOs must often look outside their walls to identify high-value external PAC partners, including skilled nursing facilities (SNFs). As a solution to this problem, the integrated health system, Partners HealthCare System (PHS) and its Pioneer ACO launched the PHS SNF Collaborative Network in October 2013 to identify and partner with high-quality SNFs. This study details the method by which PHS selected SNFs using minimum criteria based on public scores and secondary criteria based on self-reported measures, describes the characteristics of selected and nonselected SNFs, and reports SNF satisfaction with the collaborative. The selected SNFs (n=47) had significantly higher CMS Five-Star scores than the nonselected SNFs (n=93) (4.6 vs 3.2, P<.001) and were more likely than nonselected SNFs that met the minimum criteria (n=35) to have more than 5days of clinical coverage (17.0% vs 2.9%, P=.02) and to have a physician see admitted individuals within 24 (38.3% vs 17.1%, P=.02) and 48hours (93.6% vs 80.0%, P=.03). A survey sent to collaborative SNFs found high satisfaction with the process (average satisfaction, 4.6/5, with 1=very dissatisfied and 5=very satisfied, n=19). Although the challenges of improving care in SNFs remain daunting, this approach can serve as a first step toward greater clinical collaboration between acute and postacute settings that will lead to better outcomes for frail older adults. C1 [Lage, Daniel E.; Rusinak, Donna; Grabowski, David C.; Ackerly, D. Clay] Harvard Univ, Sch Med, Boston, MA USA. [Rusinak, Donna; Ackerly, D. Clay] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Rusinak, Donna; Carr, Darcy; Ackerly, D. Clay] Partners HealthCare, Boston, MA USA. [Rusinak, Donna; Carr, Darcy; Ackerly, D. Clay] Partners Continuing Care, Boston, MA USA. RP Ackerly, DC (reprint author), 165 Cambridge St,Suite 500, Boston, MA 02114 USA. EM ackerly@gmail.com FU National Institute of Aging [5T32AG02 3480-10] FX Daniel E. Lage's work was funded by National Institute of Aging Pre-Doctoral Training Grant 5T32AG02 3480-10. NR 15 TC 9 Z9 9 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 IS 4 BP 804 EP 808 DI 10.1111/jgs.13351 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CG4EB UT WOS:000353234900026 PM 25900492 ER PT J AU Evers, M Salma, N Birngruber, R Evans, CL Manstein, D AF Evers, Michael Salma, Nunciada Birngruber, Reginald Evans, Conor L. Manstein, Dieter TI REAL-TIME ANALYSIS OF METABOLIC ACTIVITY WITHIN ADIPOCYTES BY FLUORESCENCE LIFETIME IMAGING MICROSCOPY OF NADH SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Wellman Ctr Photomed, Boston, MA USA. Med Univ Lubeck, Inst Biomed Opt, D-23538 Lubeck, Germany. RI Birngruber, Reginald/Q-2342-2016 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 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2015 VL 47 IS 4 MA LB5 BP 374 EP 375 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA CG4DN UT WOS:000353233100016 ER PT J AU Lee, K Onwudiwe, O Farinelli, W Garibyan, L Anderson, RR AF Lee, Kachiu Onwudiwe, Oge Farinelli, William Garibyan, Lilit Anderson, R. Rox TI ABSORPTION SPECTRUM OF ONYCHOMYCOTIC NAILS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Lee, Kachiu; Onwudiwe, Oge; Farinelli, William; Garibyan, Lilit; Anderson, R. Rox] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2015 VL 47 IS 4 MA LB13 BP 378 EP 378 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CG4DN UT WOS:000353233100024 ER PT J AU Rizvi, I Briars, E Anbil, S Gudejko, H Xu, N Khan, S Cramer, G Celli, J Hasan, T AF Rizvi, Imran Briars, Emma Anbil, Sriram Gudejko, Heather Xu, Nan Khan, Shazia Cramer, Gwendolyn Celli, Jonathan Hasan, Tayyaba TI TARGETING BIOLOGICAL DETERMINANTS OF TREATMENT SUSCEPTIBILITY FOR PDT-BASED COMBINATIONS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2015 VL 47 IS 4 MA LB24 BP 381 EP 382 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA CG4DN UT WOS:000353233100035 ER PT J AU Schackman, BR Fleishman, JA Su, AE Berkowitz, BK Moore, RD Walensky, RP Becker, JE Voss, C Paltiel, AD Weinstein, MC Freedberg, KA Gebo, KA Losina, E AF Schackman, Bruce R. Fleishman, John A. Su, Amanda E. Berkowitz, Bethany K. Moore, Richard D. Walensky, Rochelle P. Becker, Jessica E. Voss, Cindy Paltiel, A. David Weinstein, Milton C. Freedberg, Kenneth A. Gebo, Kelly A. Losina, Elena TI The Lifetime Medical Cost Savings From Preventing HIV in the United States SO MEDICAL CARE LA English DT Article DE HIV; AIDS; health care cost; prevention; computer modeling ID ACTIVE ANTIRETROVIRAL THERAPY; HEALTH-SERVICES UTILIZATION; INFECTED PATIENTS; CARE; ERA; OUTPATIENT; HIV/AIDS; DISEASE; ADULTS; AIDS AB Objective: Enhanced HIV prevention interventions, such as pre-exposure prophylaxis for high-risk individuals, require substantial investments. We sought to estimate the medical cost saved by averting 1 HIV infection in the United States. Methods: We estimated lifetime medical costs in persons with and without HIV to determine the cost saved by preventing 1 HIV infection. We used a computer simulation model of HIV disease and treatment (CEPAC) to project CD4 cell count, antiretroviral treatment status, and mortality after HIV infection. Annual medical cost estimates for HIV-infected persons, adjusted for age, sex, race/ethnicity, and transmission risk group, were from the HIV Research Network (range, $1854-$4545/mo) and for HIV-uninfected persons were from the Medical Expenditure Panel Survey (range, $73$628/mo). Results are reported as lifetime medical costs from the US health system perspective discounted at 3% (2012 USD). Results: The estimated discounted lifetime cost for persons who become HIV infected at age 35 is $326,500 (60% for antiretroviral medications, 15% for other medications, 25% nondrug costs). For individuals who remain uninfected but at high risk for infection, the discounted lifetime cost estimate is $96,700. The medical cost saved by avoiding 1 HIV infection is $229,800. The cost saved would reach $338,400 if all HIV-infected individuals presented early and remained in care. Cost savings are higher taking into account secondary infections avoided and lower if HIV infections are temporarily delayed rather than permanently avoided. Conclusions: The economic value of HIV prevention in the United States is substantial given the high cost of HIV disease treatment. C1 [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY 10064 USA. [Fleishman, John A.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Su, Amanda E.; Berkowitz, Bethany K.; Walensky, Rochelle P.; Becker, Jessica E.; Freedberg, Kenneth A.; Losina, Elena] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Su, Amanda E.; Berkowitz, Bethany K.; Walensky, Rochelle P.; Becker, Jessica E.; Freedberg, Kenneth A.; Losina, Elena] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Moore, Richard D.; Voss, Cindy; Gebo, Kelly A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA. [Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Healthcare Policy & Res, Healthcare Policy & Res, 425 East 61st St Suite 301, New York, NY 10064 USA. EM brs2006@med.cornell.edu FU Agency for Healthcare Research and Quality, Rockville, Maryland; Health Resources and Services Administration, Rockville, Maryland FX HIVRN Sponsoring Agencies: Agency for Healthcare Research and Quality, Rockville, Maryland (Fred Hellinger, PhD, John Fleishman, PhD, Irene Fraser, PhD); Health Resources and Services Administration, Rockville, Maryland (Robert Mills, PhD, Faye Malitz, MS). NR 50 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2015 VL 53 IS 4 BP 293 EP 301 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CG3EE UT WOS:000353160100004 PM 25710311 ER PT J AU Sequist, LV AF Sequist, Lecia V. TI The Anticipated Next Season of EGFR Inhibitors SO ONCOLOGIST LA English DT Editorial Material ID CELL LUNG-CANCER; METAANALYSIS; DOCETAXEL; SURVIVAL; TRIAL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM lvsequist@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2015 VL 20 IS 4 BP 335 EP 336 DI 10.1634/theoncologist.2015-0086 PG 2 WC Oncology SC Oncology GA CG0ZD UT WOS:000353001900001 PM 25795633 ER PT J AU Lathan, CS Waldman, LT Browning, E Gagne, J Emmons, K AF Lathan, Christopher S. Waldman, Laura Tesler Browning, Emily Gagne, Joshua Emmons, Karen TI Perspectives of African Americans on Lung Cancer: A Qualitative Analysis SO ONCOLOGIST LA English DT Article DE Healthcare disparities; Lung neoplasms; Smoking cessation; Black; Qualitative research ID RACIAL-DIFFERENCES; UNITED-STATES; PATIENTS PERCEPTIONS; GROUNDED THEORY; SMOKING; EPIDEMIOLOGY; MORTALITY; BELIEFS; BEHAVIORS; KNOWLEDGE AB Background. Disparities in incidence and mortality for lung cancer in African Americans are well documented; however; the extent to which disparities reflect differences in patient perceptions of tobacco and lung cancer treatment is unclear. The objective of this study was to explore African Americans' knowledge of lung cancer, perceived risk, interest in smoking cessation, attitudes toward lung cancer treatment, and lung cancer diagnosis and treatment experiences. Patients and Methods. The cohort comprised 32 African-American current and former smokers without a cancer diagnosis who participated in focus groups and 10 African Americans with lung cancer who participated in in-depth interviews. Transcripts were analyzed using a modified grounded theory approach. Results. Participants without a cancer diagnosis were aware of the link between smoking and lung cancer, the common symptoms of the disease, and its poor prognosis. They desired specific, personalized smoking-cessation information. If diagnosed, the majority reported, they would seek medical care. Most believed that insurance and socioeconomic factors were more likely to affect treatment access than racial discrimination. Participants with a cancer diagnosis were also aware of the relationship between smoking and lung cancer. They felt their treatment plans were appropriate and trusted their physicians. Most did not believe that race affected their care. Conclusion. This qualitative study suggests that African-American smokers are aware of the relationship between smoking and lung cancer and are interested in smoking-cessation treatment. These data also indicate that lung cancer disparities are unlikely to be associated with differential willingness to receive care but that African Americans may perceive financial and insurance barriers to lung cancer treatment. C1 [Lathan, Christopher S.; Waldman, Laura Tesler; Browning, Emily; Gagne, Joshua; Emmons, Karen] Dana Farber Canc Ctr, McGraw Patterson Ctr Populat Sci, Boston, MA 02115 USA. RP Lathan, CS (reprint author), Dana Farber Canc Ctr, Canc Care Equ Program, McGraw Patterson Ctr Populat Sci, 450 Brookline Ave, Boston, MA 02115 USA. EM Christopher_Lathan@dfci.harvard FU National Cancer Institute [K01 CAl24581, 5K05CAl24415-05] FX We thank all of the study participants. We also thank Elyse Park for her valuable comments on an earlier draft. These data were presented in part at the 2010 American Association for Cancer Research conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. This study received funding from the National Cancer Institute (K01 CAl24581 and 5K05CAl24415-05). NR 46 TC 0 Z9 0 U1 2 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD APR PY 2015 VL 20 IS 4 BP 393 EP 399 DI 10.1634/theoncologist.2014-0399 PG 7 WC Oncology SC Oncology GA CG0ZD UT WOS:000353001900013 PM 25795634 ER PT J AU Brastianos, PK Cahill, DP AF Brastianos, Priscilla K. Cahill, Daniel P. TI Management of Brain Metastases in the Era of Targeted and Immunomodulatory Therapies SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID CELL LUNG-CANCER; DOSE WEEKLY ERLOTINIB; PROGNOSTIC-FACTORS; BREAST-CANCER; PHASE-2 TRIAL; OPEN-LABEL; MELANOMA; MUTATIONS; GEFITINIB; RADIOSURGERY C1 [Brastianos, Priscilla K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Brastianos, Priscilla K.] Harvard Univ, Sch Med, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Brastianos, PK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. NR 28 TC 1 Z9 1 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2015 VL 29 IS 4 BP 261 EP 263 PG 3 WC Oncology SC Oncology GA CG6TG UT WOS:000353434700006 PM 25952489 ER PT J AU Rinne, ML Wen, PY AF Rinne, Mikael L. Wen, Patrick Y. TI Treating Anaplastic Oligodendrogliomas and WHO Grade 2 Gliomas: PCV or Temozolomide? The Case for Temozolomide SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID NEWLY-DIAGNOSED GLIOBLASTOMA; RANDOMIZED-TRIAL; BRAIN-TUMOR; VINCRISTINE; LOMUSTINE; PROCARBAZINE; BEVACIZUMAB C1 [Rinne, Mikael L.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Rinne, Mikael L.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rinne, ML (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2015 VL 29 IS 4 BP 265 EP + PG 2 WC Oncology SC Oncology GA CG6TG UT WOS:000353434700008 PM 25952491 ER PT J AU Kuter, DJ AF Kuter, David J. TI Managing Thrombocytopenia Associated With Cancer Chemotherapy SO ONCOLOGY-NEW YORK LA English DT Review ID ADVANCED SOLID TUMORS; CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA; NON-HODGKIN-LYMPHOMA; CELL LUNG-CANCER; LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA; PROPHYLACTIC PLATELET TRANSFUSIONS; RECOMBINANT HUMAN THROMBOPOIETIN; MYELOSUPPRESSED RHESUS-MONKEYS; HUMAN MEGAKARYOCYTE GROWTH; COLONY-STIMULATING FACTOR AB Thrombocytopenia is a common problem in cancer patients. Aside from bleeding risk, thrombocytopenia limits chemotherapy dose and frequency. In evaluating thrombocytopenic cancer patients, it is important to asses for other causes of thrombocytopenia, including immune thrombocytopenia, coagulopathy, infection, drug reaction, post-transfusion purpura, and thrombotic microangiopathy. The incidence of chemotherapy-induced thrombocytopenia varies greatly depending on the treatment used; the highest rates of this condition are associated with gemcitabine- and platinum-based regimens. Each chemotherapy agent differs in how it causes thrombocytopenia: alkylating agents affect stem cells, cyclophosphamide affects later megakaryocyte progenitors, bortezomib prevents platelet release from megakaryocytes, and some treatments promote platelet apoptosis. Thrombopoietin is the main regulator of platelet production. In numerous studies, recombinant thrombopoietin raised the platelet count nadir, reduced the need for platelet transfusions, reduced the duration of thrombocytopenia, and allowed maintenance of chemotherapy dose intensity. Two thrombopoietin receptor agonists now available, romiplostim and eltrombopag, are potent stimulators of platelet production. Although few studies have been completed to demonstrate their ability to treat chemotherapy-induced thrombocytopenia, these agents may be useful in treating this condition in some situations. Chemotherapy dose reduction and platelet transfusions remain the major treatments for affected patients. C1 [Kuter, David J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7858,55 Fruit St, Boston, MA 02114 USA. EM dkuter@MGH.harvard.edu FU Bristol-Myers Squibb; GlaxoSmithKline; Ono FX Dr. Kuter is a consultant to 3SBio, Amgen, Kirin, and Pfizer. He receives research funding from Bristol-Myers Squibb, GlaxoSmithKline, and Ono. NR 114 TC 7 Z9 7 U1 0 U2 7 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2015 VL 29 IS 4 BP 282 EP 294 PG 13 WC Oncology SC Oncology GA CG6TG UT WOS:000353434700009 PM 25952492 ER PT J AU Kou, S Rett, D AF Kou, Sandra Rett, Doug TI Various SD-OCT Features of Focal Choroidal Excavations SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE SD-OCT; enhanced depth imaging; autofluorescence; focal choroidal excavation ID OPTICAL COHERENCE TOMOGRAPHY; EYES AB Purpose. To describe the clinical and spectral domain optical coherence tomography (OCT) features of two cases of focal choroidal excavation (FCE) and to review relevant literature to increase awareness and understanding of this rare condition. Case Report. Spectral domain OCT, enhanced depth imaging, and fundus autofluorescence (short wavelength and near infrared) were used to study two cases of FCE. Both patients were asymptomatic and maintained good vision at 6 months follow-up despite one case showing progression from a conforming-to a nonconforming-type FCE. At both lesion sites, the sclerochoroidal junction was unaltered, and the overlying retinal layers (retinal nerve fiber layer to outer plexiform layer) also remained intact. Enhanced depth imaging revealed an absence or compression of outer choroidal layers beneath the excavation and the presence of abnormally large choroidal vessels adjacent to the excavation. The near-infrared autofluorescence showed improved ability to highlight the FCE lesion compared with traditional short-wavelength autofluorescence. Conclusions. Focal choroidal excavation is a rare, often asymptomatic macular condition. It appears on funduscopic examination as retinal pigment epithelial abnormalities, but its true structure is revealed with OCT. Certain spectral domain OCT imaging modalities, such as enhanced depth imaging and short and near-infrared autofluorescence, are helpful to monitor these lesions and to better understand its pathophysiology as it relates to choroidal vascular abnormalities. C1 [Kou, Sandra; Rett, Doug] VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Kou, S (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM Sandra.u.kou@gmail.com NR 16 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-5488 EI 1538-9235 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD APR PY 2015 VL 92 IS 4 SU 1 BP S59 EP S66 PG 8 WC Ophthalmology SC Ophthalmology GA CG6NX UT WOS:000353420000013 PM 25756338 ER PT J AU Shahi, A Eajazi, A AF Shahi, Alisina Eajazi, Alireza TI Prevention of Periprosthetic Joint Infection: Pre- and Intraoperative Considerations SO ORTHOPEDICS LA English DT Editorial Material ID SURGICAL SITE INFECTION; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; REVISION TOTAL HIP; UNITED-STATES; GLOVE PERFORATION; ORTHOPEDIC-SURGERY; ADHESIVE DRAPE; AIR-FLOW; SURVIVORSHIP C1 [Shahi, Alisina] Thomas Jefferson Univ, Rothman Inst, Philadelphia, PA 19107 USA. [Eajazi, Alireza] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Musculoskeletal Div, Boston, MA 02114 USA. RP Eajazi, A (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Musculoskeletal Div, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM aeajazi@mgh.harvard.edu NR 31 TC 0 Z9 0 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 EI 1938-2367 J9 ORTHOPEDICS JI Orthopedics PD APR PY 2015 VL 38 IS 4 BP 219 EP 221 DI 10.3928/01477447-20150402-02 PG 3 WC Orthopedics SC Orthopedics GA CG5QH UT WOS:000353347700018 PM 25901611 ER PT J AU Lyons, KD Svensborn, IA Kornblith, AB Hegel, MT AF Lyons, Kathleen D. Svensborn, Ingrid A. Kornblith, Alice B. Hegel, Mark T. TI A Content Analysis of Functional Recovery Strategies of Breast Cancer Survivors SO OTJR-OCCUPATION PARTICIPATION AND HEALTH LA English DT Article DE breast neoplasm; occupational therapy; rehabilitation ID QUALITY-OF-LIFE; PARTICIPATION RESTRICTIONS; LONG-TERM; REHABILITATION; CHEMOTHERAPY; METAANALYSIS; LIMITATIONS; DEPRESSION; DIAGNOSIS; NEEDS AB Seventeen breast cancer survivors completed a 6-week, telephone-delivered, behavioral activation/problem-solving intervention designed to reduce participation restrictions. A content analysis of the session data was conducted to identify the goals and patterns of goal attainment and to understand what women were trying to achieve in their recovery. The 17 women set 141 goals. Sixty-six (47%) of the goals reflected a desire to add a new activity to their routine and 75 (53%) of the goals reflected a desire to perform a routine activity more efficiently. The women primarily set goals to address challenges in exercising (24%), work (13%), nutrition (11%), instrumental activities of daily living (IADLs; 10%), stress management (9%), and social activities (9%). The women set an average of 8 goals and met 71% of their goals. The intervention shows promise in helping women set and achieve a number of functional goals as part of breast cancer recovery. C1 [Lyons, Kathleen D.; Svensborn, Ingrid A.; Hegel, Mark T.] Dartmouth Coll, Hanover, NH 03755 USA. [Lyons, Kathleen D.; Svensborn, Ingrid A.; Hegel, Mark T.] Norris Cotton Canc Ctr, Canc Control Program, Lebanon, NH USA. [Kornblith, Alice B.] Dana Farber Canc Inst, Breast Oncol Program, Boston, MA 02115 USA. RP Lyons, KD (reprint author), Dartmouth Coll, Geisel Sch Med Dartmouth, DHMC, 7750 Psychiat Dept,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Kathleen.D.Lyons@dartmouth.edu FU National Cancer Institute [1 R21 CA140849-01]; American Cancer Society [MRSG-12-113-01-CPPB] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant to Dr. Hegel from the National Cancer Institute (1 R21 CA140849-01). The first author was supported by a Mentored Research Scholar Grant in Applied and Clinical Research, MRSG-12-113-01-CPPB from the American Cancer Society. NR 32 TC 0 Z9 0 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1539-4492 EI 1938-2383 J9 OTJR-OCCUP PART HEAL JI OTJR-Occup. Particip. Health PD APR PY 2015 VL 35 IS 2 BP 73 EP 80 DI 10.1177/1539449214567306 PG 8 WC Rehabilitation SC Rehabilitation GA CG7AA UT WOS:000353453100002 PM 26460469 ER PT J AU Westra, SJ Brody, AS Mahani, MG Guillerman, RP Hegde, SV Iyer, RS Lee, EY Newman, B Podberesky, DJ Thacker, PG AF Westra, Sjirk J. Brody, Alan S. Mahani, Maryam Ghadimi Guillerman, R. Paul Hegde, Shilpa V. Iyer, Ramesh S. Lee, Edward Y. Newman, Beverley Podberesky, Daniel J. Thacker, Paul G. TI The incidental pulmonary nodule in a child Part 1: recommendations from the SPR Thoracic Imaging Committee regarding characterization, significance and follow-up SO PEDIATRIC RADIOLOGY LA English DT Review DE Chest; Computed tomography; Fleischner criteria; Pediatric; Incidental findings; Lung; Lung cancer; Lung nodule ID SQUAMOUS-CELL-CARCINOMA; CYSTIC ADENOMATOID MALFORMATION; CT HALO SIGN; BRONCHIOLOALVEOLAR CARCINOMA; LUNG-CANCER; COMPUTED-TOMOGRAPHY; FLEISCHNER-SOCIETY; SOLID NODULES; PEDIATRIC POPULATION; YOUNG-PATIENTS AB No guidelines are in place for the follow-up and management of pulmonary nodules that are incidentally detected on CT in the pediatric population. The Fleischner guidelines, which were developed for the older adult population, do not apply to children. This review summarizes the evidence collected by the Society for Pediatric Radiology (SPR) Thoracic Imaging Committee in its attempt to develop pediatric-specific guidelines. Small pulmonary opacities can be characterized as linear or as ground-glass or solid nodules. Linear opacities and ground-glass nodules are extremely unlikely to represent an early primary or metastatic malignancy in a child. In our review, we found a virtual absence of reported cases of a primary pulmonary malignancy presenting as an incidentally detected small lung nodule on CT in a healthy immune-competent child. Because of the lack of definitive information on the clinical significance of small lung nodules that are incidentally detected on CT in children, the management of those that do not have the typical characteristics of an intrapulmonary lymph node should be dictated by the clinical history as to possible exposure to infectious agents, the presence of an occult immunodeficiency, the much higher likelihood that the nodule represents a metastasis than a primary lung tumor, and ultimately the individual preference of the child's caregiver. Nodules appearing in children with a history of immune deficiency, malignancy or congenital pulmonary airway malformation should not be considered incidental, and their workup should be dictated by the natural history of these underlying conditions. C1 [Westra, Sjirk J.] Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. [Brody, Alan S.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol CH 1, Cincinnati, OH 45229 USA. [Mahani, Maryam Ghadimi] Univ Michigan Hlth Syst, Sect Pediat Radiol, Dept Radiol, CS Mott Childrens Hosp, Ann Arbor, MI USA. [Guillerman, R. Paul] Texas Childrens Hosp, Dept Radiol, Houston, TX 77030 USA. [Hegde, Shilpa V.] Arkansas Childrens Hosp, Dept Radiol, Little Rock, AR 72202 USA. [Iyer, Ramesh S.] Seattle Childrens Hosp, Dept Radiol, Seattle, WA USA. [Lee, Edward Y.] Boston Childrens Hosp, Dept Pediat Radiol, Boston, MA USA. [Newman, Beverley] Stanford Univ, Dept Radiol, Lucile Packard Childrens Hosp, Stanford, CA 94305 USA. [Podberesky, Daniel J.] Nemours Childrens Hosp, Dept Radiol, Orlando, FL USA. [Thacker, Paul G.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, 34 Fruit St,White 246A, Boston, MA 02114 USA. EM swestra@partners.org RI Guillerman, Robert/R-1531-2016 OI Guillerman, Robert/0000-0001-8149-613X NR 60 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD APR PY 2015 VL 45 IS 5 BP 628 EP 633 DI 10.1007/s00247-014-3267-7 PG 6 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CG4EA UT WOS:000353234800002 PM 25655369 ER PT J AU Westra, SJ Thacker, PG Podberesky, DJ Lee, EY Iyer, RS Hegde, SV Guillerman, RP Mahani, MG AF Westra, Sjirk J. Thacker, Paul G. Podberesky, Daniel J. Lee, Edward Y. Iyer, Ramesh S. Hegde, Shilpa V. Guillerman, R. Paul Mahani, Maryam Ghadimi TI The incidental pulmonary nodule in a child Part 2: Commentary and suggestions for clinical management, risk communication and prevention SO PEDIATRIC RADIOLOGY LA English DT Review DE Chest; Computed tomography; Fleischner criteria; Pediatric; Incidental findings; Lung; Lung cancer; Lung nodule ID CHEST COMPUTED-TOMOGRAPHY; INFORMED-CONSENT; PECTUS EXCAVATUM; DECISION-MAKING; LUNG-DISEASE; IONIZING-RADIATION; PEDIATRIC TRAUMA; ABDOMINAL CT; WHITE PAPER; X-RAY AB The incidental detection of small lung nodules in children is a vexing consequence of an increased reliance on CT. We present an algorithm for the management of lung nodules detected on CT in children, based on the presence or absence of symptoms, the presence or absence of elements in the clinical history that might explain these nodules, and the imaging characteristics of the nodules (such as attenuation measurements within the nodule). We provide suggestions on how to perform a thoughtfully directed and focused search for clinically occult extrathoracic disease processes (including malignant disease) that may present as an incidentally detected lung nodule on CT. This algorithm emphasizes that because of the lack of definitive information on the natural history of small solid nodules that are truly detected incidentally, their clinical management is highly dependent on the caregivers' individual risk tolerance. In addition, we present strategies to reduce the prevalence of these incidental findings, by preventing unnecessary chest CT scans or inadvertent inclusion of portions of the lungs in scans of adjacent body parts. Application of these guidelines provides pediatric radiologists with an important opportunity to practice patient-centered and evidence-based medicine. C1 [Westra, Sjirk J.] Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. [Thacker, Paul G.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [Podberesky, Daniel J.] Nemours Childrens Hosp, Dept Radiol, Orlando, FL USA. [Lee, Edward Y.] Boston Childrens Hosp, Dept Pediat Radiol, Boston, MA USA. [Iyer, Ramesh S.] Seattle Childrens Hosp, Dept Radiol, Seattle, WA USA. [Hegde, Shilpa V.] Arkansas Childrens Hosp, Dept Radiol, Little Rock, AR 72202 USA. [Guillerman, R. Paul] Texas Childrens Hosp, Dept Radiol, Houston, TX 77030 USA. [Mahani, Maryam Ghadimi] Univ Michigan Hlth Syst, Dept Radiol, Sect Pediat Radiol, CS Mott Childrens Hosp, Ann Arbor, MI USA. RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, 34 Fruit St,White 246A, Boston, MA 02114 USA. EM swestra@partners.org RI Guillerman, Robert/R-1531-2016 OI Guillerman, Robert/0000-0001-8149-613X NR 47 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD APR PY 2015 VL 45 IS 5 BP 634 EP 639 DI 10.1007/s00247-014-3269-5 PG 6 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CG4EA UT WOS:000353234800003 PM 25655370 ER PT J AU Mammarella, ND Cheng, ZY Fu, ZQ Daudi, A Bolwell, GP Dong, XN Ausubel, FM AF Mammarella, Nicole D. Cheng, Zhenyu Fu, Zheng Qing Daudi, Arsalan Bolwell, G. Paul Dong, Xinnian Ausubel, Frederick M. TI Apoplastic peroxidases are required for salicylic acid-mediated defense against Pseudomonas syringae SO PHYTOCHEMISTRY LA English DT Article DE Arabidopsis thaliana; Peroxidases; Oxidative burst; Salicylic acid signaling; Microbial associated molecular patterns; Pattern triggered immunity; Effector triggered immunity ID SYSTEMIC ACQUIRED-RESISTANCE; PLANT-DISEASE RESISTANCE; CLONED AVIRULENCE GENE; CLASS-III PEROXIDASES; NBS-LRR PROTEINS; OXIDATIVE BURST; ARABIDOPSIS-THALIANA; NONHOST RESISTANCE; PV PHASEOLICOLA; TOMATO DC3000 AB Reactive oxygen species (ROS) generated by NADPH oxidases or apoplastic peroxidases play an important role in the plant defense response. Diminished expression of at least two Arabidopsis thaliana peroxidase encoding genes, PRX33 (At3g49110) and PRX34 (At3g49120), as a consequence of anti-sense expression of a heterologous French bean peroxidase gene (asFBP1.1), were previously shown to result in reduced levels of ROS following pathogen attack, enhanced susceptibility to a variety of bacterial and fungal pathogens, and reduced levels of callose production and defense-related gene expression in response to the microbe associated molecular pattern (MAMP) molecules flg22 and elf26. These data demonstrated that the peroxidase-dependent oxidative burst plays an important role-in the elicitation of pattern-triggered immunity (PTI). Further work reported in this paper, however, shows that asFBP1.1 antisense plants are not impaired in all PTI-associated responses. For example, some but not all flg22-elicited genes are induced to lower levels by flg22 in asFPB1.1, and callose deposition in asFPB1.1 is similar to wild-type following infiltration with a Pseudomonas syringae hrcC mutant or with non-host P. syringae pathovars. Moreover, asFPB1.1 plants did not exhibit any apparent defect in their ability to mount a hypersensitive response (HR). On the other hand, salicylic acid (SA)-mediated activation of PR1 was dramatically impaired in asFPB1.1 plants. In addition, P. syringae-elicited expression of many genes known to be SA-dependent was significantly reduced in asFBP1.1 plants. Consistent with this latter result, in asFBP1.1 plants the key regulator of SA-mediated responses, NPR1, showed both dramatically decreased total protein abundance and a failure to monomerize, which is required for its translocation into the nucleus. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mammarella, Nicole D.; Cheng, Zhenyu; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Mammarella, Nicole D.; Cheng, Zhenyu; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fu, Zheng Qing; Dong, Xinnian] Duke Univ, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Dept Biol, Durham, NC 27708 USA. [Daudi, Arsalan; Bolwell, G. Paul] Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NIH [R37 GM48707, R01 GM069594]; NSF [MCB-0519898]; Biotechnology and Biological Science Research Council Grant [BB/E021166]; Natural Sciences and Engineering Research Council of Canada; Hargitt Fellowship FX This work was supported by NIH Grants R37 GM48707 awarded to F.M.A. and R01 GM069594 awarded to X.D., NSF Grant MCB-0519898 awarded to X.D. and F.M.A., and Biotechnology and Biological Science Research Council Grant BB/E021166 awarded to G.P.B. Z.C. was a recipient of a Postdoctoral Fellowship and a Banting Postdoctoral Fellowship from the Natural Sciences and Engineering Research Council of Canada. Z.Q.F. was a recipient of the Hargitt Fellowship. X.D. is a Howard Hughes Medical Institute-Gordon and Betty Moore Foundation investigator. NR 52 TC 9 Z9 9 U1 3 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD APR PY 2015 VL 112 BP 110 EP 121 DI 10.1016/j.phytochem.2014.07.010 PG 12 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA CG2GU UT WOS:000353093700013 PM 25096754 ER PT J AU Fang, MA Heiney, C Yentes, JM Harada, ND Masih, S Perell-Gerson, KL AF Fang, Meika A. Heiney, Constance Yentes, Jennifer M. Harada, Nancy D. Masih, Sulabha Perell-Gerson, Karen L. TI Effects of Contralateral Versus Ipsilateral Cane Use on Gait in People with Knee Osteoarthritis SO PM&R LA English DT Article ID RADIOGRAPHIC DISEASE PROGRESSION; EULAR RECOMMENDATIONS; HIP; PAIN; CLASSIFICATION; MANAGEMENT; MOMENTS; FORCE; USAGE; RISK AB Objective: To compare the immediate effects of contralateral versus ipsilateral cane use on spatiotemporal gait parameters and peak vertical ground force in overweight or obese adults with symptomatic knee osteoarthritis (OA). Design: Prospective observational study. Setting: An academic tertiary Veterans Affairs Healthcare Center. Participants: Thirty-eight overweight or obese subjects with symptomatic knee OA who had not used a cane for the past 30 days. Methods: Spatiotemporal gait data were obtained with an optical motion capture system while subjects walked without a cane, with a cane contralateral to the more painful lower limb, or with a cane ipsilateral to the more painful lower limb at self-selected speeds. An in-shoe dynamic pressure distribution system was used to measure the vertical ground reaction force. Main Outcome Measurements: Spatiotemporal measures of gait and peak vertical ground reaction force on both lower limbs were recorded for each walking condition: no cane, contralateral cane, and ipsilateral cane. Results: Walking with a cane either contralateral or ipsilateral to the more symptomatic limb led to significant reductions in gait velocity (14%-16%), cadence (12%-14%), and peak vertical ground reaction force (normalized for body weight; 11%-12%) on the more painful lower limb compared with walking unaided (P < .05). There were no significant differences in the peak vertical ground reaction force on either lower limbs when comparing walking with a cane contralateral to the more painful limb or walking with a cane ipsilateral to the more painful limb. Subjects also experienced a significant decrease in gait velocity with contralateral or ipsilateral cane use compared with walking without a cane; the lower walking speed was due to a decrease in cadence. Conclusions: These results support the prescription of a single-point cane to offload a lower limb with painful knee OA by holding the cane either ipsilateral or contralateral to the more painful lower limb. C1 [Fang, Meika A.; Heiney, Constance; Harada, Nancy D.; Masih, Sulabha; Perell-Gerson, Karen L.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fang, Meika A.; Harada, Nancy D.; Masih, Sulabha] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Yentes, Jennifer M.] Univ Nebraska, Nebraska Biomech Core Facil, Omaha, NE 68182 USA. [Perell-Gerson, Karen L.] Georgia Gwinnett Coll, Sch Sci & Technol, Lawrenceville, GA USA. RP Fang, MA (reprint author), VA West Los Angeles Healthcare Ctr, Rheumatol Sect, 111J,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM meika.fang@va.gov OI Yentes, Jennifer/0000-0001-6550-7759 FU Veterans Affairs Office of Research and Development, Rehabilitation Research and Development Service [F3873R] FX This work was supported by the Veterans Affairs Office of Research and Development, Rehabilitation Research and Development Service (grant F3873R; ClinicalTrials.gov identifier No. NCT00223795). NR 36 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD APR PY 2015 VL 7 IS 4 BP 400 EP 406 DI 10.1016/j.pmrj.2014.09.018 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CG2QZ UT WOS:000353120900007 PM 25305371 ER PT J AU Juncadella, AC Alame, AM Sands, LR Deshpande, AR AF Juncadella, Anna C. Alame, Amer M. Sands, Laurence R. Deshpande, Amar R. TI Perianal Crohn's disease: A review SO POSTGRADUATE MEDICINE LA English DT Review DE Perianal; Crohn's disease; medical; surgical; management; fistula ID INFLAMMATORY-BOWEL-DISEASE; SINGLE-CENTER EXPERIENCE; FISTULA-IN-ANO; MAINTENANCE THERAPY; LONG-TERM; CERTOLIZUMAB PEGOL; ANAL-FISSURE; DOUBLE-BLIND; ENDOSCOPIC ULTRASOUND; METRONIDAZOLE THERAPY AB Perianal involvement in Crohn's disease (CD), which encompasses fistulas, ulcers, abscesses, strictures and cancer, can lead to significant impairment in quality of life. The objective of this article is to review the major perianal complications of CD and the current medical and surgical modalities used to treat them. Antibiotics are commonly used despite a lack of controlled trials to validate their use and should be used as a bridge to maintenance therapy. The anti-metabolites azathioprine and 6-MP have shown a positive response in terms of fistula closure, although these data are mostly from trials looking at this as a secondary endpoint. Infliximab is an effective agent for induction and maintenance of treatment of fistulizing CD. Further studies to evaluate the use of subcutaneous anti-tumor necrosis factors are needed to convincingly prove their efficacy for perianal fistulizing disease. In CD, clinicians should avoid surgery as a first-line approach for skin tags, hemorrhoids or fissures in the setting of proctitis. Surgery, particularly lateral internal sphincterotomy, in combination with medical therapy is associated with higher fissure healing rates in the absence of proctitis. Fistulotomy is curative for most simple low perianal fistulae, but complex fistulas often require sphincter-sparing surgical procedures. Less invasive approaches such as a chemical sphincterotomy should be used first, with therapy escalated only if this fails. C1 [Juncadella, Anna C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alame, Amer M.] St John Hosp & Med Ctr, Dept Surg, Div Colon & Rectal Surg, Grosse Pointe Woods, MI USA. [Sands, Laurence R.] Univ Miami, Miller Sch Med, Dept Surg, Div Colon & Rectal Surg, Miami, FL 33136 USA. [Deshpande, Amar R.] Univ Miami, Miller Sch Med, Dept Med, Div Gastroenterol, Miami, FL 33136 USA. RP Juncadella, AC (reprint author), Massachusetts Gen Hosp, Dept Med, 1 Emerson Pl,Apt 11-E, Boston, MA 02114 USA. EM annajuncadella@gmail.com NR 88 TC 1 Z9 2 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD APR PY 2015 VL 127 IS 3 BP 266 EP 272 DI 10.1080/00325481.2015.1023160 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CG7AO UT WOS:000353454500002 PM 25746229 ER PT J AU Myung, W Won, HH Fava, M Mischoulon, D Yeung, A Lee, D Kim, DK Jeon, HJ AF Myung, Woojae Won, Hong-Hee Fava, Maurizio Mischoulon, David Yeung, Albert Lee, Dongsoo Kim, Doh Kwan Jeon, Hong Jin TI Celebrity Suicides and Their Differential Influence on Suicides in the General Population: A National Population-Based Study in Korea SO Psychiatry Investigation LA English DT Article DE Celebrity; Suicide; South Korea; Effect size ID MEDIA COVERAGE; RATES; METAANALYSIS; ASSOCIATION; PREVENTION; WALES; ACTS AB Objective Although evidence suggests that there is an increase in suicide rates in the general population following celebrity suicide, the rates are heterogeneous across celebrities and countries. It is unclear which is the more vulnerable population according to the effect sizes of celebrity suicides to general population. Methods All suicide victims in the general population verified by the Korea National Statistical Office and suicides of celebrity in South Korea were included for 7 years from 2005 to 2011. Effect sizes were estimated by comparing rates of suicide in the population one month before and after each celebrity suicide. The associations between suicide victims and celebrities were examined. Results Among 94,845 suicide victims, 17,209 completed suicide within one month after 13 celebrity suicides. Multivariate logistic regression analyses revealed that suicide victims who died after celebrity suicide were significantly likely to be of age 20-39, female, and to die by hanging. These qualities were more strongly associated among those who followed celebrity suicide with intermediate and high effect sizes than lower. Younger suicide victims were significantly associated with higher effect size, female gender, white collar employment, unmarried status, higher education, death by hanging, and night-time death. Characteristics of celebrities were significantly associated with those of general population in hanging method and gender. Conclusion Individuals who commit suicide after a celebrity suicide are likely to be younger, female, and prefer hanging as method of suicide, which are more strongly associated in higher effect sizes of celebrity suicide. C1 [Myung, Woojae; Lee, Dongsoo; Kim, Doh Kwan; Jeon, Hong Jin] Sungkyunkwan Univ, Dept Psychiat, Depress Ctr, Samsung Med Ctr,Sch Med, Seoul 135710, South Korea. [Won, Hong-Hee] Sungkyunkwan Univ, Samsung Biomed Res Inst, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea. [Fava, Maurizio; Mischoulon, David; Yeung, Albert; Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Jeon, Hong Jin] Sungkyunkwan Univ, Dept Clin Res Design & Evaluat, Samsung Adv Inst Hlth Sci & Technol, Seoul 135710, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, Dept Med Device Management & Res, Samsung Adv Inst Hlth Sci & Technol, Seoul 135710, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Dept Psychiat, Depress Ctr, Samsung Med Ctr,Sch Med, 81 Irwon Ro, Seoul 135710, South Korea. EM jeonhj@skku.edu RI Kim, Doh Kwan/F-4616-2014 FU National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461]; Korea National Statistical Office (KNSO); Korea Press Foundation FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064). This research was also supported by the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SMO1131461. We appreciate the Korea National Statistical Office (KNSO) and the Korea Press Foundation for their support and cooperation. NR 28 TC 1 Z9 1 U1 1 U2 5 PU KOREAN NEUROPSYCHIATRIC ASSOC PI SEOUL PA RN 522, G-FIVE CENTRAL PLAZA 1685-8 SEOCHO 4-DONG, SEOCHO-GU, SEOUL, 137-882, SOUTH KOREA SN 1738-3684 EI 1976-3026 J9 PSYCHIAT INVEST JI Psychiatry Investig. PD APR PY 2015 VL 12 IS 2 BP 204 EP 211 DI 10.4306/pi.2015.12.2.204 PG 8 WC Psychiatry SC Psychiatry GA CG5WW UT WOS:000353367600008 PM 25866521 ER PT J AU Hartshorne, JK Germine, LT AF Hartshorne, Joshua K. Germine, Laura T. TI When Does Cognitive Functioning Peak? The Asynchronous Rise and Fall of Different Cognitive Abilities Across the Life Span SO PSYCHOLOGICAL SCIENCE LA English DT Article DE cognitive ability; cognitive development; intelligence; individual differences; language development ID WORKING-MEMORY; AGE; INTELLIGENCE; ADULTHOOD; INTERNET; SCALE; SPEED; MIND AB Understanding how and when cognitive change occurs over the life span is a prerequisite for understanding normal and abnormal development and aging. Most studies of cognitive change are constrained, however, in their ability to detect subtle, but theoretically informative life-span changes, as they rely on either comparing broad age groups or sparse sampling across the age range. Here, we present convergent evidence from 48,537 online participants and a comprehensive analysis of normative data from standardized IQ and memory tests. Our results reveal considerable heterogeneity in when cognitive abilities peak: Some abilities peak and begin to decline around high school graduation; some abilities plateau in early adulthood, beginning to decline in subjects' 30s; and still others do not peak until subjects reach their 40s or later. These findings motivate a nuanced theory of maturation and age-related decline, in which multiple, dissociable factors differentially affect different domains of cognition. C1 [Hartshorne, Joshua K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Germine, Laura T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Hartshorne, JK (reprint author), MIT, Brain & Cognit Sci, 1 Longfellow Pl,Apartment 2223, Boston, MA 02114 USA. EM jharts@mit.edu OI Germine, Laura/0000-0001-8690-8412 FU National Defense Science and Engineering Graduate Fellowship; National Research Service Awards from the National Institutes of Health [5F32HD072748, 1F32MH10297]; National Science Foundation's Graduate Research Fellowship Program FX This research was funded by a National Defense Science and Engineering Graduate Fellowship to J. K. Hartshorne, National Research Service Awards from the National Institutes of Health to J. K. Hartshorne (5F32HD072748) and L. T. Germine (1F32MH10297), and an award from the National Science Foundation's Graduate Research Fellowship Program to L. T. Germine. NR 42 TC 29 Z9 30 U1 3 U2 32 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 EI 1467-9280 J9 PSYCHOL SCI JI Psychol. Sci. PD APR PY 2015 VL 26 IS 4 BP 433 EP 443 DI 10.1177/0956797614567339 PG 11 WC Psychology, Multidisciplinary SC Psychology GA CG0UI UT WOS:000352986600008 PM 25770099 ER PT J AU Pandharipande, PV Heberle, C Dowling, EC Kong, CY Tramontano, A Perzan, KE Brugge, W Hur, C AF Pandharipande, Pari V. Heberle, Curtis Dowling, Emily C. Kong, Chung Yin Tramontano, Angela Perzan, Katherine E. Brugge, William Hur, Chin TI Targeted Screening of Individuals at High Risk for Pancreatic Cancer: Results of a Simulation Model SO RADIOLOGY LA English DT Article ID SINGLE-INSTITUTION EXPERIENCE; PAPILLARY MUCINOUS NEOPLASMS; MEDICAL DECISION-MAKING; SERVICES TASK-FORCE; COST-EFFECTIVENESS; LUNG-CANCER; LIFE EXPECTANCY; FAMILY-HISTORY; CLINICOPATHOLOGICAL CHARACTERISTICS; 1423 PANCREATICODUODENECTOMIES AB Purpose: To identify when, from the standpoint of relative risk, magnetic resonance (MR) imaging-based screening may be effective in patients with a known or suspected genetic predisposition to pancreatic cancer. Materials and Methods: The authors developed a Markov model of pancreatic ductal adenocarcinoma (PDAC). The model was calibrated to National Cancer Institute Surveillance, Epidemiology, and End Results registry data and informed by the literature. A hypothetical screening strategy was evaluated in which all population individuals underwent one-time MR imaging screening at age 50 years. Screening outcomes for individuals with an average risk for PDAC ("base case") were compared with those for individuals at an increased risk to assess for differential benefits in populations with a known or suspected genetic predisposition. Effects of varying key inputs, including MR imaging performance, surgical mortality, and screening age, were evaluated with a sensitivity analysis. Results: In the base case, screening resulted in a small number of cancer deaths averted (39 of 100 000 men, 38 of 100 000 women) and a net decrease in life expectancy (23 days for men, 24 days for women), which was driven by unnecessary pancreatic surgeries associated with false-positive results. Life expectancy gains were achieved if an individual's risk for PDAC exceeded 2.4 (men) or 2.7 (women) times that of the general population. When relative risk increased further, for example to 30 times that of the general population, averted cancer deaths and life expectancy gains increased substantially (1219 of 100 000 men, life expectancy gain: 65 days; 1204 of 100 000 women, life expectancy gain: 71 days). In addition, results were sensitive to MR imaging specificity and the surgical mortality rate. Conclusion: Although PDAC screening with MR imaging for the entire population is not effective, individuals with even modestly increased risk may benefit. C1 [Pandharipande, Pari V.; Heberle, Curtis; Dowling, Emily C.; Kong, Chung Yin; Tramontano, Angela; Perzan, Katherine E.; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Pandharipande, Pari V.; Heberle, Curtis; Dowling, Emily C.; Kong, Chung Yin; Tramontano, Angela] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Perzan, Katherine E.; Brugge, William; Hur, Chin] Massachusetts Gen Hosp, Dept Gen Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 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 OI Heberle, Curtis/0000-0003-1445-5420; Hur, Chin/0000-0002-2819-7576 FU National Institutes of Health [K07CA133097] FX This research was supported by the National Institutes of Health (grant K07CA133097). NR 64 TC 8 Z9 8 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2015 VL 275 IS 1 BP 177 EP 187 DI 10.1148/radiol.14141282 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG4KW UT WOS:000353255000021 PM 25393849 ER PT J AU Emblem, KE Pinho, MC Zollner, FG Due-Tonnessen, P Hald, JK Schad, LR Meling, TR Rapalino, O Bjornerud, A AF Emblem, Kyrre E. Pinho, Marco C. Zollner, Frank G. Due-Tonnessen, Paulina Hald, John K. Schad, Lothar R. Meling, Torstein R. Rapalino, Otto Bjornerud, Atle TI A Generic Support Vector Machine Model for Preoperative Glioma Survival Associations SO RADIOLOGY LA English DT Article ID CEREBRAL BLOOD-VOLUME; DYNAMIC SUSCEPTIBILITY CONTRAST; GLIOBLASTOMA-MULTIFORME; PROGNOSTIC-FACTORS; HISTOGRAM ANALYSIS; GRADE GLIOMA; MRI; DIFFUSION; ALGORITHMS; MAPS AB Purpose: To develop a generic support vector machine (SVM) model by using magnetic resonance (MR) imaging-based blood volume distribution data for preoperative glioma survival associations and to prospectively evaluate the diagnostic effectiveness of this model in autonomous patient data. Materials and Methods: Institutional and regional medical ethics committees approved the study, and all patients signed a consent form. Two hundred thirty-five preoperative adult patients from two institutions with a subsequent histologically confirmed diagnosis of glioma after surgery were included retrospectively. An SVM learning technique was applied to MR imaging-based whole-tumor relative cerebral blood volume (rCBV) histograms. SVM models with the highest diagnostic accuracy for 6-month and 1-, 2-, and 3-year survival associations were trained on 101 patients from the first institution. With Cox survival analysis, the diagnostic effectiveness of the SVM models was tested on independent data from 134 patients at the second institution. Results were adjusted for known survival predictors, including patient age, tumor size, neurologic status, and postsurgery treatment, and were compared with survival associations from an expert reader. Results: Compared with total qualitative assessment by an expert reader, the whole-tumor rCBV-based SVM model was the strongest parameter associated with 6-month and 1-, 2-, and 3-year survival in the independent patient data (area under the receiver operating characteristic curve, 0.794-0.851; hazard ratio, 5.4-21.2). Discussion: Machine learning by means of SVM in combination with whole-tumor rCBV histogram analysis can be used to identify early patient survival in aggressive gliomas. The SVM model returned higher diagnostic accuracy values than an expert reader, and the model appears to be insensitive to patient, observer, and institutional variations. C1 [Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Intervent Ctr, N-0372 Oslo, Norway. [Due-Tonnessen, Paulina; Hald, John K.] Oslo Univ Hosp, Dept Radiol, N-0372 Oslo, Norway. [Meling, Torstein R.] Oslo Univ Hosp, Dept Neurosurg, N-0372 Oslo, Norway. [Emblem, Kyrre E.; Pinho, Marco C.; Rapalino, Otto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Emblem, Kyrre E.; Pinho, Marco C.; Rapalino, Otto] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Emblem, Kyrre E.; Pinho, Marco C.; Rapalino, Otto] Harvard Univ, Sch Med, Boston, MA USA. [Pinho, Marco C.] Univ Texas Southwestern Med Ctr, Dept Radiol, Dallas, TX USA. [Zollner, Frank G.; Schad, Lothar R.] Heidelberg Univ, Med Fac Mannheim, Dept Comp Assisted Clin Med, Heidelberg, Germany. [Bjornerud, Atle] Univ Oslo, Dept Phys, Oslo, Norway. RP Emblem, KE (reprint author), Oslo Univ Hosp, Intervent Ctr, N-0027 Sognsvannsveien 20, N-0372 Oslo, Norway. EM kyrre@nmr.mgh.harvard.edu RI Zollner, Frank/A-2725-2012; Emblem, Kyrre/H-6691-2012; OI Zollner, Frank/0000-0003-3405-1394; Emblem, Kyrre/0000-0002-6580-9519; Pinho, Marco/0000-0002-4645-1638 NR 24 TC 2 Z9 2 U1 2 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 APR PY 2015 VL 275 IS 1 BP 228 EP 234 DI 10.1148/radiol.14140770 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG4KW UT WOS:000353255000026 PM 25486589 ER PT J AU Harvey, HB Gilman, MD Wu, CC Cushing, MS Halpern, EF Zhao, J Pandharipande, PV Shepard, JAO Alkasab, TK AF Harvey, H. Benjamin Gilman, Matthew D. Wu, Carol C. Cushing, Matthew S. Halpern, Elkan F. Zhao, Jing Pandharipande, Pari V. Shepard, Jo-Anne O. Alkasab, Tarik K. TI Diagnostic Yield of Recommendations for Chest CT Examination Prompted by Outpatient Chest Radiographic Findings SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; FOLLOW-UP; CANCER; COST; RISK; CARE AB Purpose: To evaluate the diagnostic yield of recommended chest computed tomography (CT) prompted by abnormalities detected on outpatient chest radiographic images. Materials and Methods: This HIPAA-compliant study had institutional review board approval; informed consent was waived. Reports of all outpatient chest radiographic examinations performed at a large academic center during 2008 (n = 29 138) were queried to identify studies that included a recommendation for a chest CT imaging. The radiology information system was queried for these patients to determine if a chest CT examination was obtained within 1 year of the index radiographic examination that contained the recommendation. For chest CT examinations obtained within 1 year of the index chest radiographic examination and that met inclusion criteria, chest CT images were reviewed to determine if there was an abnormality that corresponded to the chest radiographic finding that prompted the recommendation. All corresponding abnormalities were categorized as clinically relevant or not clinically relevant, based on whether further work-up or treatment was warranted. Groups were compared by using t test and Fisher exact test with a Bonferroni correction applied for multiple comparisons. Results: There were 4.5% (1316 of 29138 [95% confidence interval {CI}: 4.3%, 4.8%]) of outpatient chest radiographic examinations that contained a recommendation for chest CT examination, and increasing patient age (P < .001) and positive smoking history (P = .001) were associated with increased likelihood of a recommendation for chest CT examination. Of patients within this subset who met inclusion criteria, 65.4% (691 of 1057 [95% CI: 62.4%, 68.2%) underwent a chest CT examination within the year after the index chest radiographic examination. Clinically relevant corresponding abnormalities were present on chest CT images in 41.4% (286 of 691 [95% CI: 37.7%, 45.2%]) of cases, nonclinically relevant corresponding abnormalities in 20.6% (142 of 691 [95% CI: 17.6%, 23.8%]) of cases, and no corresponding abnormalities in 38.1% (263 of 691 [95% CI: 34.4%, 41.8%]) of cases. Newly diagnosed, biopsy-proven malignancies were detected in 8.1% (56 of 691 [95% CI: 6.2%, 10.4%]) of cases. Conclusion: A radiologist recommendation for chest CT to evaluate an abnormal finding on an outpatient chest radiographic examination has a high yield of clinically relevant findings. C1 [Harvey, H. Benjamin; Gilman, Matthew D.; Wu, Carol C.; Halpern, Elkan F.; Pandharipande, Pari V.; Shepard, Jo-Anne O.; Alkasab, Tarik K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Pandharipande, Pari V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. [Zhao, Jing] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Cushing, Matthew S.] Adv Med Imaging, Denver, CO USA. RP Alkasab, TK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA. EM talkasab@mgh.harvard.edu FU National Institutes of Health and National Cancer Institute [NIH/NCI K07133097] FX This research was supported by the National Institutes of Health and National Cancer Institute (grant number NIH/NCI K07133097). NR 16 TC 2 Z9 2 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2015 VL 275 IS 1 BP 262 EP 271 DI 10.1148/radiol.14140583 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG4KW UT WOS:000353255000030 PM 25531242 ER PT J AU Marcus, EA Wozniak, LJ Venick, RS Ponthieux, SM Cheng, EY Farmer, DG AF Marcus, E. A. Wozniak, L. J. Venick, R. S. Ponthieux, S. M. Cheng, E. Y. Farmer, D. G. TI Successful Term Pregnancy in an Intestine-Pancreas Transplant Recipient With Chronic Graft Dysfunction and Parenteral Nutrition Dependence: A Case Report SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID LIVER-TRANSPLANTATION; TACROLIMUS; PATIENT; REPRODUCTION; INFANTS AB Pregnancy after solid organ transplantation is becoming more common, with the largest recorded numbers in renal and liver transplant recipients. Intestinal transplantation is relatively new compared to other solid organs, and reports of successful pregnancy are far less frequent. All pregnancies reported to date in intestinal transplant recipients have been in women with stable graft function. The case reported here involves the first reported successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and dependence on both transplant immunosuppression and parenteral nutrition (PN) at the time of conception. Pregnancy was unplanned and unexpected in the setting of chronic illness and menstrual irregularities, discovered incidentally on abdominal ultrasound at approximately 18 weeks' gestation. Rapamune was held, tacrolimus continued, and PN adjusted to maintain consistent weight gain. A healthy female infant was delivered vaginally at term. Medical complications during pregnancy included anemia and need for tunneled catheter replacements. Ascites and edema were improved from baseline, with recurrence of large volume ascites shortly after delivery. Successful pregnancy is possible in the setting of transplant immunosuppression, chronic intestinal graft dysfunction, and long-term PN requirement, but close monitoring is required to ensure the health of mother and child. C1 [Marcus, E. A.; Wozniak, L. J.; Venick, R. S.] Univ Calif Los Angeles, DGSOM, Dept Pediat, Los Angeles, CA 90095 USA. [Marcus, E. A.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Venick, R. S.; Ponthieux, S. M.; Cheng, E. Y.; Farmer, D. G.] Univ Calif Los Angeles, DGSOM, Dept Surg, Dumont UCLA Transplant Ctr, Los Angeles, CA 90095 USA. RP Marcus, EA (reprint author), Univ Calif Los Angeles, DGSOM, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, 10833 LeConte Ave,12-383 MDCC, Los Angeles, CA 90095 USA. EM emarcus@mednet.ucla.edu FU NIDDK NIH HHS [K08 DK100661] NR 31 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 EI 1873-2623 J9 TRANSPL P JI Transplant. Proc. PD APR PY 2015 VL 47 IS 3 BP 863 EP 867 DI 10.1016/j.transproceed.2015.01.009 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA CG6PT UT WOS:000353424900068 PM 25724255 ER PT J AU Dasenbrock, HH Chiocca, EA AF Dasenbrock, Hormuzdiyar H. Chiocca, E. Antonio TI Skull Base Chordomas and Chondrosarcomas: A Population-Based Analysis SO WORLD NEUROSURGERY LA English DT Editorial Material DE Chondrosarcoma; Chordoma; Outcomes; Prognosis; Skull base ID CRANIAL BASE; CLIVAL CHORDOMAS; FOLLOW-UP; MANAGEMENT; SURGERY C1 [Chiocca, E. Antonio] Harvard Univ, Sch Med, Brigham & Womens Faulkner Hosp, Dept Neurosurg,Inst Neurosci, Boston, MA 02138 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Faulkner Hosp, Dept Neurosurg,Inst Neurosci, Boston, MA 02138 USA. EM eachiocca@partners.org NR 29 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD APR PY 2015 VL 83 IS 4 BP 468 EP 470 DI 10.1016/j.wneu.2014.08.049 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CG1NJ UT WOS:000353039500016 PM 25169743 ER PT J AU Neagu, MR Huang, RY Reardon, DA Wen, PY AF Neagu, Martha R. Huang, Raymond Y. Reardon, David A. Wen, Patrick Y. TI How Treatment Monitoring Is Influencing Treatment Decisions in Glioblastomas SO CURRENT TREATMENT OPTIONS IN NEUROLOGY LA English DT Review DE Glioblastoma; RANO; Chemoradiation; Pseudoprogression; Pseudoresponse; Radiation necrosis; Temozolomide ID HIGH-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; SINGLE-AGENT BEVACIZUMAB; RANDOMIZED PHASE-III; RECURRENT GLIOBLASTOMA; TUMOR PROGRESSION; MALIGNANT GLIOMA; FOLLOW-UP; C-11-METHIONINE PET; RESPONSE ASSESSMENT AB Opinion Statement Glioblastoma (GBM), the most common malignant primary tumor in adults, carries a dismal prognosis with an average median survival of 14-16 months. The current standard of care for newly diagnosed GBM consists of maximal safe resection followed by fractionated radiotherapy combined with concurrent temozolomide and 6 to 12 cycles of adjuvant temozolomide. The determination of treatment response and clinical decision-making in the treatment of GBM depends on accurate radiographic assessment. Differentiating treatment response from tumor progression is challenging and combines long-term follow-up using standard MRI, with assessing clinical status and corticosteroid dependency. At progression, bevacizumab is the mainstay of treatment. Incorporation of antiangiogenic therapies leads to rapid blood-brain barrier normalization with remarkable radiographic response often not accompanied by the expected survival benefit, further complicating imaging assessment. Improved radiographic interpretation criteria, such as the Response Assessment in Neuro-Oncology (RANO) criteria, incorporate non-enhancing disease but still fall short of definitely distinguishing tumor progression, pseudoresponse, and pseudoprogression. With new evolving treatment modalities for this devastating disease, advanced imaging modalities are increasingly becoming part of routine clinical care in a field where neuroimaging has such essential role in guiding treatment decisions and defining clinical trial eligibility and efficacy. C1 [Neagu, Martha R.; Reardon, David A.; Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neagu, Martha R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Huang, Raymond Y.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Huang, RY (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM ryhuang@partners.org OI Huang, Raymond/0000-0001-7661-797X NR 98 TC 1 Z9 1 U1 2 U2 9 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1092-8480 EI 1534-3138 J9 CURR TREAT OPTION NE JI Curr. Treat. Options Neurol. PD APR PY 2015 VL 17 IS 4 AR 15 DI 10.1007/s11940-015-0343-8 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA CF2BJ UT WOS:000352351900002 ER PT J AU Kanzaria, HK Hoffman, JR Probst, MA Caloyeras, JP Berry, SH Brook, RH AF Kanzaria, Hemal K. Hoffman, Jerome R. Probst, Marc A. Caloyeras, John P. Berry, Sandra H. Brook, Robert H. TI Emergency Physician Perceptions of Medically Unnecessary Advanced Diagnostic Imaging SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID EVIDENCE-BASED MEDICINE; MINOR HEAD TRAUMA; US HEALTH-CARE; DECISION-MAKING; DEFENSIVE MEDICINE; PERFORMANCE-MEASURES; DEPARTMENT PATIENTS; NATIONAL TRENDS; COST; MALPRACTICE AB ObjectivesThe objective was to determine emergency physician (EP) perceptions regarding 1) the extent to which they order medically unnecessary advanced diagnostic imaging, 2) factors that contribute to this behavior, and 3) proposed solutions for curbing this practice. MethodsAs part of a larger study to engage physicians in the delivery of high-value health care, two multispecialty focus groups were conducted to explore the topic of decision-making around resource utilization, after which qualitative analysis was used to generate survey questions. The survey was extensively pilot-tested and refined for emergency medicine (EM) to focus on advanced diagnostic imaging (i.e., computed tomography [CT] or magnetic resonance imaging [MRI]). The survey was then administered to a national, purposive sample of EPs and EM trainees. Simple descriptive statistics to summarize physician responses are presented. ResultsIn this study, 478 EPs were approached, of whom 435 (91%) completed the survey; 68% of respondents were board-certified, and roughly half worked in academic emergency departments (EDs). Over 85% of respondents believe too many diagnostic tests are ordered in their own EDs, and 97% said at least some (mean= 22%) of the advanced imaging studies they personally order are medically unnecessary. The main perceived contributors were fear of missing a low-probability diagnosis and fear of litigation. Solutions most commonly felt to be extremely or very helpful for reducing unnecessary imaging included malpractice reform (79%), increased patient involvement through education (70%) and shared decision-making (56%), feedback to physicians on test-ordering metrics (55%), and improved education of physicians on diagnostic testing (50%). ConclusionsOverordering of advanced imaging may be a systemic problem, as many EPs believe a substantial proportion of such studies, including some they personally order, are medically unnecessary. Respondents cited multiple complex factors with several potential high-yield solutions that must be addressed simultaneously to curb overimaging. C1 [Kanzaria, Hemal K.] Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA USA. [Kanzaria, Hemal K.] US Dept Vet Affairs, Los Angeles, CA USA. [Kanzaria, Hemal K.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hoffman, Jerome R.] Univ Calif Los Angeles, Ctr Emergency Med, Los Angeles, CA 90024 USA. [Probst, Marc A.] Mt Sinai Med Ctr, Dept Emergency Med, New York, NY 10029 USA. [Caloyeras, John P.; Berry, Sandra H.; Brook, Robert H.] RAND Corp, Santa Monica, CA USA. [Caloyeras, John P.] Pardee RAND Grad Sch, Santa Monica, CA USA. [Brook, Robert H.] Univ Calif Los Angeles, David Geffen Sch Med, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. RP Kanzaria, HK (reprint author), Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA USA. EM hkanzaria@mednet.ucla.edu FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Foundation Clinical Scholars program; National Heart, Lung, and Blood Institute of the National Institutes of Health [5K12 HL109005] FX This work was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Foundation Clinical Scholars program (Dr. Kanzaria) and the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number 5K12 HL109005 (Dr. Probst). The funding agencies 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 70 TC 26 Z9 26 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2015 VL 22 IS 4 SI SI BP 390 EP 398 DI 10.1111/acem.12625 PG 9 WC Emergency Medicine SC Emergency Medicine GA CF5BN UT WOS:000352569900002 PM 25807868 ER PT J AU Kanzaria, HK Brook, RH Probst, MA Harris, D Berry, SH Hoffman, JR AF Kanzaria, Hemal K. Brook, Robert H. Probst, Marc A. Harris, Dustin Berry, Sandra H. Hoffman, Jerome R. TI Emergency Physician Perceptions of Shared Decision-making SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID PRIMARY-CARE; WORKFORCE; MEDICINE AB ObjectivesDespite the potential benefits of shared decision-making (SDM), its integration into emergency care is challenging. Emergency physician (EP) perceptions about the frequency with which they use SDM, its potential to reduce medically unnecessary diagnostic testing, and the barriers to employing SDM in the emergency department (ED) were investigated. MethodsAs part of a larger project examining beliefs on overtesting, questions were posed to EPs about SDM. Qualitative analysis of two multispecialty focus groups was done exploring decision-making around resource use to generate survey items. The survey was then pilot-tested and revised to focus on advanced diagnostic imaging and SDM. The final survey was administered to EPs recruited at four emergency medicine (EM) conferences and 15 ED group meetings. This report addresses responses regarding SDM. ResultsA purposive sample of 478 EPs from 29 states were approached, of whom 435 (91%) completed the survey. EPs estimated that, on average, multiple reasonable management options exist in over 50% of their patients and reported employing SDM with 58% of such patients. Respondents perceived SDM as a promising solution to reduce overtesting. However, despite existing research to the contrary, respondents also commonly cited beliefs that 1) many patients prefer that the physician decides, 2) when offered a choice, many patients opt for more aggressive care than they need, and 3) it is too complicated for patients to know how to choose. ConclusionsMost surveyed EPs believe SDM is a potential high-yield solution to overtesting, but many perceive patient-related barriers to its successful implementation. C1 [Kanzaria, Hemal K.] Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA 90024 USA. [Kanzaria, Hemal K.] Univ Calif Los Angeles, US Dept Vet Affairs, Los Angeles, CA USA. [Brook, Robert H.; Harris, Dustin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brook, Robert H.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA USA. [Hoffman, Jerome R.] Univ Calif Los Angeles, Ctr Emergency Med, Los Angeles, CA 90024 USA. [Brook, Robert H.; Berry, Sandra H.] RAND Corp, Santa Monica, CA USA. [Probst, Marc A.] Mt Sinai Med Ctr, Dept Emergency Med, New York, NY 10029 USA. RP Kanzaria, HK (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA 90024 USA. EM hkanzaria@mednet.ucla.edu FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Foundation Clinical Scholars program; National Heart, Lung and Blood Institute of the National Institutes of Health [5K12 HL109005] FX This work was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Foundation Clinical Scholars program (Dr. Kanzaria) and the National Heart, Lung and Blood Institute of the National Institutes of Health under Award Number 5K12 HL109005 (Dr. Probst). The funding agencies 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 7 TC 22 Z9 22 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2015 VL 22 IS 4 SI SI BP 399 EP 405 DI 10.1111/acem.12627 PG 7 WC Emergency Medicine SC Emergency Medicine GA CF5BN UT WOS:000352569900003 PM 25807995 ER PT J AU Tirrell, G Sri-on, J Lipsitz, LA Camargo, CA Kabrhel, C Liu, SW AF Tirrell, Gregory Sri-on, Jiraporn Lipsitz, Lewis A. Camargo, Carlos A., Jr. Kabrhel, Christopher Liu, Shan W. TI Evaluation of Older Adult Patients With Falls in the Emergency Department: Discordance With National Guidelines SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PREVENTING FALLS; ELDERLY PERSONS; MULTIFACTORIAL INTERVENTION; CLINICAL-PRACTICE; RECURRENT FALLS; RISK ASSESSMENT; COMMUNITY; PEOPLE; CARE AB ObjectivesThe objective was to examine whether the emergency department (ED) evaluation of older adult fallers is concordant with the Geriatric Emergency Department Guidelines. MethodsThis study was a chart review of randomly selected older adult ED fall patients from one urban academic teaching hospital. Patients 65years and older who had ED fall visits in 2012 and who had primary care physicians within our hospital network during the past 3years were included. Transferred patients were excluded. The data collection instrument was adapted from ED fall evaluation recommendations. ResultsThere were 350 patients in this study. The mean (SD) patient age was 80.1 (+/- 8.8) years, 124 (35%) were male, 327 (93%) were white, and 298 (85%) were community dwelling. The range with which history and physical examination findings were concordant with fall guidelines was 1% to 85%. Cause and location of fall were the two most frequently reported history items (85 and 81%, respectively), while asking about baseline vision was only reported 1% of the time. Evaluating for sensory deficits and muscle strength were the two most frequently reported physical examinations (63 and 48%, respectively), while balance was evaluated with the lowest frequency (1%). Patients who received more guideline-recommended evaluations were older with more comorbid conditions and were transferred to an observation unit or admitted to the hospital more frequently. Overall, more than half of these elderly patients (56%) were discharged from the ED to their place of preadmission residence. ConclusionsThe current ED evaluation of older adult fallers is discordant with general and ED-specific fall guidelines. Future studies are warranted to investigate ways to successfully implement fall evaluation guidelines. C1 [Tirrell, Gregory; Sri-on, Jiraporn; Camargo, Carlos A., Jr.; Kabrhel, Christopher; Liu, Shan W.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Sri-on, Jiraporn] Navamindhadhiraj Univ, Vajira Hosp, Dept Emergency Med, Bangkok, Thailand. [Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Lipsitz, Lewis A.] Harvard Univ, Sch Med, Inst Aging Res Hebrew SeniorLife, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tirrell, G (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM gtirrell@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU Hartford Foundation's Center of Excellence FX Funded by the Hartford Foundation's Center of Excellence. NR 52 TC 5 Z9 5 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2015 VL 22 IS 4 SI SI BP 461 EP 467 DI 10.1111/acem.12634 PG 7 WC Emergency Medicine SC Emergency Medicine GA CF5BN UT WOS:000352569900011 PM 25773899 ER PT J AU Scales, CD Lin, L Saigal, CS Bennett, CJ Ponce, NA Mangione, CM Litwin, MS AF Scales, Charles D., Jr. Lin, Li Saigal, Christopher S. Bennett, Carol J. Ponce, Ninez A. Mangione, Carol M. Litwin, Mark S. CA NIDDK Urologic Dis Amer Project TI Emergency Department Revisits for Patients with Kidney Stones in California SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID UNITED-STATES; MANAGEMENT; DISEASE; UROLITHIASIS; PREVALENCE; PATTERNS; VISITS; CARE AB ObjectivesKidney stones affect nearly one in 11 persons in the United States, and among those experiencing symptoms, emergency care is common. In this population, little is known about the incidence of and factors associated with repeat emergency department (ED) visits. The objective was to identify associations between potentially mutable factors and the risk of an ED revisit for patients with kidney stones in a large, all-payer cohort. MethodsThis was a retrospective cohort study of all patients in California initially treated and released from EDs for kidney stones between February 2008 and November 2009. A multivariable regression model was created to identify associations between patient-level characteristics, area health care resources, processes of care, and the risk of repeat ED visits. The primary outcome was a second ED visit within 30days of the initial discharge from emergent care. ResultsAmong 128,564 patients discharged from emergent care, 13,684 (11%) had at least one additional emergent visit for treatment of their kidney stone. In these patients, nearly one in three required hospitalization or an urgent temporizing procedure at the second visit. On multivariable analysis, the risk of an ED revisit was associated with insurance status (e.g., Medicaid vs. private insurance; odds ratio [OR]= 1.52, 95% confidence interval [CI]=1.43 to 1.61; p<0.001). Greater access to urologic care was associated with lower odds of an ED revisit (highest quartile OR= 0.88, 95% CI=0.80 to 0.97; p<0.01 vs. lowest quartile). In exploratory models, performance of a complete blood count was associated with a decreased odds of revisit (OR=0.86, 95% CI=0.75 to 0.97; p=0.02). ConclusionsRepeat high-acuity care affects one in nine patients discharged from initial emergent evaluations for kidney stones. Access to urologic care and processes of care are associated with lower risk of repeat emergent encounters. Efforts are indicated to identify preventable causes of ED revisits for kidney stone patients and design interventions to reduce the risk of high-cost, high-acuity, repeat care. C1 [Scales, Charles D., Jr.; Lin, Li] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27708 USA. [Scales, Charles D., Jr.] Duke Univ, Sch Med, Div Urol Surg, Durham, NC USA. [Scales, Charles D., Jr.; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Robert Wood Johnson Fdn, VA Clin Scholars Program, Los Angeles, CA 90095 USA. [Saigal, Christopher S.; Bennett, Carol J.; Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Bennett, Carol J.] Greater Los Angeles Vet Hlth Syst, Los Angeles, CA USA. [Saigal, Christopher S.; Litwin, Mark S.] RAND Corp, Santa Monica, CA USA. [Ponce, Ninez A.; Mangione, Carol M.; Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Scales, CD (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27708 USA. EM chuck.scales@duke.edu OI Ponce, Ninez/0000-0001-5151-6718 FU Robert Wood Johnson Foundation; VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program; UCLA Robert Wood Johnson Clinical Scholars Program; U.S. Department of Veterans Affairs [67799]; University of California at Los Angeles (UCLA); Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly under National Institutes of Health (NIH)/NIA [P30-AG021684]; NIH/National Center for Advancing Translational Sciences UCLA Clinical and Translational Science Institute Grant [UL1TR000124]; Barbara A. Levey and Gerald S. Levey Endowed Chair in Medicine; National Institute of Diabetes and Digestive and Kidney Diseases [HHSN276201200016C]; National Library of Medicine FX Dr. Scales was supported by the Robert Wood Johnson Foundation and the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program.; Dr. Mangione received support from the UCLA Robert Wood Johnson Clinical Scholars Program and the U.S. Department of Veterans Affairs (Grant 67799), the University of California at Los Angeles (UCLA), Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly under National Institutes of Health (NIH)/NIA Grant P30-AG021684, and from NIH/National Center for Advancing Translational Sciences UCLA Clinical and Translational Science Institute Grant UL1TR000124. Dr. Mangione holds the Barbara A. Levey and Gerald S. Levey Endowed Chair in Medicine, which partially supported her work.; The Urologic Diseases in America Project is supported by Grant HHSN276201200016C from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Library of Medicine. NR 19 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2015 VL 22 IS 4 SI SI BP 468 EP 474 DI 10.1111/acem.12632 PG 7 WC Emergency Medicine SC Emergency Medicine GA CF5BN UT WOS:000352569900012 PM 25779695 ER PT J AU Olds, PK Kiwanuka, JP Ware, NC Tsai, AC Haberer, JE AF Olds, Peter K. Kiwanuka, Julius P. Ware, Norma C. Tsai, Alexander C. Haberer, Jessica E. TI Explaining Antiretroviral Therapy Adherence Success Among HIV-Infected Children in Rural Uganda: A Qualitative Study SO AIDS AND BEHAVIOR LA English DT Article DE Antiretroviral therapy; Human immunodeficiency virus; Adherence; Children; Uganda ID SUB-SAHARAN AFRICA; HUMAN-IMMUNODEFICIENCY-VIRUS; CAREGIVER TRAINING-PROGRAM; RESOURCE-LIMITED SETTINGS; MEDICATION ADHERENCE; SOCIAL SUPPORT; FOOD INSECURITY; YOUNG-CHILDREN; MOBILE PHONES; BARRIERS AB High adherence is critical for achieving clinical benefits of HIV antiretroviral therapy (ART) and particularly challenging for children. We conducted 35 qualitative interviews with caregivers of HIV-infected Ugandan children who were followed in a longitudinal study of real-time ART adherence monitoring; 18 participants had undetectable HIV RNA, while 17 had detectable virus. Interviews blinded to viral suppression status elicited information on adherence experiences, barriers and facilitators to adherence, and social support. Using an inductive content analytic approach, we identified 'lack of resources,' 'Lazarus effect,' 'caregiver's sense of obligation and commitment,' and 'child's personal responsibility' as categories of influence on adherence, and defined types of caregiver social support. Among children with viral suppression, high hopes for the child's future and ready access to private instrumental support appeared particularly important. These findings suggest clinical counseling should explore caregivers' views of their children's futures and ability to access support in overcoming adherence barriers. C1 [Olds, Peter K.] Harvard Univ, Sch Med, Boston, MA USA. [Kiwanuka, Julius P.] Mbarara Univ Sci & Technol, Dept Paediat, Mbarara, Uganda. [Ware, Norma C.] Harvard Univ, Sch Med, Dept Psychiat, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.; Haberer, Jessica E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, MGH Ctr Global Hlth, Dept Med, Boston, MA 02114 USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, MGH Ctr Global Hlth, Ctr Global Hlth, Boston, MA 02114 USA. RP Haberer, JE (reprint author), Massachusetts Gen Hosp, MGH Ctr Global Hlth, Dept Med, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM jhaberer@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes Health [K23MH087228, K24MH090894]; Harvard Medical School Class of 1984 Scholarship; NIH [K23MH096620] FX All authors contributed to the conception and design of the study, data analysis and interpretation, and/or development of the manuscript. The manuscript was drafted by P.K.O. and J.E.H. All authors critically reviewed the manuscript, suggested revisions and editorial changes, and approved the final version. The authors would like to thank the study participants, as well as the following study staff: Flavia Ninsiima, Ambrose Mugyenyi, Sarah Namwanje, Constance Katabazi, and Teddy Komuhangi. Financial support for the qualitative research presented here was provided by U.S. National Institutes Health K23MH087228 (J.E.H.) and K24MH090894 (N.C.W.), and the Harvard Medical School Class of 1984 Scholarship (P.K.O.). The authors also acknowledge salary support from NIH K23MH096620 (A.C.T.). A preliminary version of this work have been presented by P.K.O. at the 7th International Conference on HIV Treatment and Prevention Adherence, Miami, FL, June 3-5, 2012 (Abs. Number 80075). NR 62 TC 1 Z9 1 U1 3 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2015 VL 19 IS 4 BP 584 EP 593 DI 10.1007/s10461-014-0924-7 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CF6AI UT WOS:000352638400002 PM 25323679 ER PT J AU Katz, IT Dietrich, J Tshabalala, G Essien, T Rough, K Wright, AA Bangsberg, DR Gray, GE Ware, NC AF Katz, Ingrid T. Dietrich, Janan Tshabalala, Gugu Essien, Thandekile Rough, Kathryn Wright, Alexi A. Bangsberg, David R. Gray, Glenda E. Ware, Norma C. TI Understanding Treatment Refusal Among Adults Presenting for HIV-Testing in Soweto, South Africa: A Qualitative Study SO AIDS AND BEHAVIOR LA English DT Article DE Antiretroviral refusal; Engagement in care; South Africa; Treatment refusal; Linkage to care; ART initiation ID ANTIRETROVIRAL THERAPY; SERODISCORDANT COUPLES; STIGMA; ART; PREVENTION; INITIATION; ADHERENCE; UGANDA; KENYA; AIDS AB HIV treatment initiatives have focused on increasing access to antiretroviral therapy (ART). There is growing evidence, however, that treatment availability alone is insufficient to stop the epidemic. In South Africa, only one third of individuals living with HIV are actually on treatment. Treatment refusal has been identified as a phenomenon among people who are asymptomatic, however, factors driving refusal remain poorly understood. We interviewed 50 purposively sampled participants who presented for voluntary counseling and testing in Soweto to elicit a broad range of detailed perspectives on ART refusal. We then integrated our core findings into an explanatory framework. Participants described feeling "too healthy" to start treatment, despite often having a diagnosis of AIDS. This subjective view of wellness was framed within the context of treatment being reserved for the sick. Taking ART could also lead to unintended disclosure and social isolation. These data provide a novel explanatory model of treatment refusal, recognizing perceived risks and social costs incurred when disclosing one's status through treatment initiation. Our findings suggest that improving engagement in care for people living with HIV in South Africa will require optimizing social integration and connectivity for those who test positive. C1 [Katz, Ingrid T.; Rough, Kathryn] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02120 USA. [Katz, Ingrid T.; Wright, Alexi A.; Bangsberg, David R.; Ware, Norma C.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Ingrid T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Dietrich, Janan; Tshabalala, Gugu; Essien, Thandekile; Gray, Glenda E.] Perinatal HIV Res Unit, Soweto, South Africa. [Rough, Kathryn] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wright, Alexi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1620 Tremont St,3rd Floor BWH, Boston, MA 02120 USA. EM ikatz2@partners.org FU U.S. National Institutes of Health [5 K23MH09766703]; NIH [P30 AI060354]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; NIDDK; NIGMS; FIC; OAR FX This publication was made possible with funding from U.S. National Institutes of Health 5 K23MH09766703, and help from the Harvard University Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NIDDK, NIGMS, FIC, and OAR. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 11 Z9 11 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2015 VL 19 IS 4 BP 704 EP 714 DI 10.1007/s10461-014-0920-y PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CF6AI UT WOS:000352638400015 PM 25304330 ER PT J AU Copen, WA Deipolyi, AR Schaefer, PW Schwamm, LH Gonzalez, RG Wu, O AF Copen, W. A. Deipolyi, A. R. Schaefer, P. W. Schwamm, L. H. Gonzalez, R. G. Wu, O. TI Exposing Hidden Truncation-Related Errors in Acute Stroke Perfusion Imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBRAL-BLOOD-FLOW; ARTERIAL INPUT FUNCTION; ACUTE ISCHEMIC-STROKE; SINGULAR-VALUE DECOMPOSITION; TEMPORAL RESOLUTION; COMPUTED-TOMOGRAPHY; VOLUME MEASUREMENTS; CLUSTER-ANALYSIS; CT PARAMETERS; TRANSIT-TIME AB BACKGROUND AND PURPOSE: The durations of acute ischemic stroke patients' CT or MR perfusion scans may be too short to fully sample the passage of the injected contrast agent through the brain. We tested the potential magnitude of hidden errors related to the truncation of data by short perfusion scans. MATERIALS AND METHODS: Fifty-seven patients with acute ischemic stroke underwent perfusion MR imaging within 12 hours of symptom onset, using a relatively long scan duration (110 seconds). Shorter scan durations (39.5-108.5 seconds) were simulated by progressively deleting the last-acquired images. CBV, CBF, MTT, and time to response function maximum (Tmax) were measured within DWI-identified acute infarcts, with commonly used postprocessing algorithms. All measurements except Tmax were normalized by dividing by the contralateral hemisphere values. The effects of the scan duration on these hemodynamic measurements and on the volumes of lesions with Tmax of >6 seconds were tested using regression. RESULTS: Decreasing scan duration from 110 seconds to 40 seconds falsely reduced perfusion estimates by 47.6%-64.2% of normal for CBV, 1.96%-4.10% for CBF, 133%-205% for MTT, and 6.2-8.0 seconds for Tmax, depending on the postprocessing method. This truncation falsely reduced estimated Tmax lesion volume by 71.5 or 93.8 mL, depending on the deconvolution method. Lesion reversal (ie, change from above-normal to apparently normal, or from >6 seconds to 6 seconds for the time to response function maximum) with increasing truncation occurred in 37%-46% of lesions for CBV, 2%-4% for CBF, 28%-54% for MTT, and 42%-44% for Tmax, depending on the postprocessing method. CONCLUSIONS: Hidden truncation-related errors in perfusion images may be large enough to alter patient management or affect outcomes of clinical trials. C1 [Copen, W. A.; Deipolyi, A. R.; Schaefer, P. W.; Gonzalez, R. G.; Wu, O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Schwamm, L. H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Copen, WA (reprint author), Massachusetts Gen Hosp, Neuroradiol GRB 273A, 55 Fruit St, Boston, MA 02114 USA. EM wcopen@partners.org FU National Institutes of Health [P50NS051343, R01NS059775, R01NS063925] FX This work was supported by National Institutes of Health grants P50NS051343, R01NS059775, and R01NS063925. NR 31 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2015 VL 36 IS 4 BP 638 EP 645 DI 10.3174/ajnr.A4186 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CF4IO UT WOS:000352512400012 PM 25500309 ER PT J AU Baer, AH Hoff, BA Srinivasan, A Galban, CJ Mukherji, SK AF Baer, A. H. Hoff, B. A. Srinivasan, A. Galban, C. J. Mukherji, S. K. TI Feasibility Analysis of the Parametric Response Map as an Early Predictor of Treatment Efficacy in Head and Neck Cancer SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID FUNCTIONAL DIFFUSION MAP; SQUAMOUS-CELL CARCINOMA; BIOMARKER; STATISTICS; MRI AB BACKGROUND AND PURPOSE: Estimating changes in the volume transfer constant, normalized area under the contrast-enhancement time curve at 60 seconds, and fractional blood plasma volume by using dynamic contrast-enhanced MR imaging may be useful in predicting tumor response to chemoradiation. We hypothesized that the parametric response map, a voxel-by-voxel analysis of quantitative dynamic contrast-enhanced MR imaging maps, predicts survival in patients with head and neck cancer. MATERIALS AND METHODS: Ten patients with locoregionally advanced head and neck squamous cell carcinoma underwent definitive concurrent chemoradiation therapy. For each patient, dynamic contrast-enhanced MR imaging data were collected before and 2 weeks after treatment initiation. Change in perfusion parameters within the primary tumor volume with time was analyzed by parametric response mapping and by whole-tumor mean percentage change. Outcome was defined as overall survival. The perfusion parameter and metric most predictive of outcome were identified. Overall survival was estimated by the log-rank test and Kaplan-Meier survival curve. RESULTS: The volume transfer constant and normalized area under the contrast-enhancement time curve at 60 seconds were predictive of survival both in parametric response map analysis (volume transfer constant, P = .002; normalized area under the contrast-enhancement time curve at 60 seconds, P = .02) and in the percentage change analysis (volume transfer constant, P = .04; normalized area under the contrast-enhancement time curve at 60 seconds, P = .02). Blood plasma volume predicted survival in neither analysis. CONCLUSIONS: Parametric response mapping of MR perfusion biomarkers could potentially guide treatment modification in patients with predicted treatment failure. Larger studies are needed to determine whether parametric response map analysis or percentage signal change in these perfusion parameters is the stronger predictor of survival. C1 [Baer, A. H.; Hoff, B. A.; Srinivasan, A.; Galban, C. J.] Univ Michigan Hlth Syst, Dept Radiol, Ann Arbor, MI USA. [Mukherji, S. K.] Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. RP Baer, AH (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Gray 2,Room 273A,55 Fruit St, Boston, MA 02114 USA. EM aaronbaer@gmail.com FU William N. Hanafee, MD, Research Seed Grant; National Institutes of Health [P50CA093990, P01CA059827, P01CA085878] FX This work was supported by the William N. Hanafee, MD, Research Seed Grant (2011-2012) and the following National Institutes of Health grants: P50CA093990, P01CA059827, P01CA085878. NR 20 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2015 VL 36 IS 4 BP 757 EP 762 DI 10.3174/ajnr.A4296 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CF4IO UT WOS:000352512400029 PM 25792532 ER PT J AU Koudriavtseva, T Sbardella, E Mainero, C AF Koudriavtseva, T. Sbardella, E. Mainero, C. TI Brain Perfusion and Vasoreactivity in Multiple Sclerosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter C1 [Koudriavtseva, T.; Sbardella, E.] Ist Fisioterapici Ospitalieri, Regina Elena Natl Canc Inst, Neurol Unit, Multiple Sclerosis Ctr, Rome, Italy. [Mainero, C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mainero, C.] Harvard Univ, Sch Med, Boston, MA USA. RP Koudriavtseva, T (reprint author), Ist Fisioterapici Ospitalieri, Regina Elena Natl Canc Inst, Neurol Unit, Multiple Sclerosis Ctr, Rome, Italy. RI Sbardella, Emilia/K-2167-2016 OI Sbardella, Emilia/0000-0002-9129-9065 NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2015 VL 36 IS 4 BP E27 EP E28 DI 10.3174/ajnr.A4249 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CF4IO UT WOS:000352512400001 PM 25593205 ER PT J AU Lust, B Flynn, S Sherman, JC Gair, J Henderson, CR Cordella, C Whitlock, J Mancuso, S Chen, Z Costigan, A Immerman, A AF Lust, Barbara Flynn, Suzanne Sherman, Janet Cohen Gair, James Henderson, Charles R., Jr. Cordella, Claire Whitlock, Jordan Mancuso, Sarah Chen, Zhong Costigan, Aileen Immerman, Alex TI Reversing Ribot: Does regression hold in language of prodromal Alzheimer's disease? SO BRAIN AND LANGUAGE LA English DT Article DE Language; Mild cognitive impairment; Aging; Ribot; Regression hypothesis; Child development ID MILD COGNITIVE IMPAIRMENT; RETROGRADE-AMNESIA; TERM-MEMORY; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; HUNTINGTONS-DISEASE; NATIONAL INSTITUTE; SEMANTIC DEMENTIA; TEMPORAL GRADIENT; DEFAULT NETWORK AB We consider the regression or retrogenesis hypothesis, which argues that order of acquisition in development is reversed in neurodegeneration or pathology. Originally proposed as a regression hypothesis for the study of memory disorders, specifically retrograde amnesia, by Ribot (1881), it has been extended to the study of brain aging and pathology and to language. We Investigate this hypothesis in a new study of language development, aging, and pathology. Through interuniversity collaboration using a matched experimental design and task, we compare production of complex sentences containing relative clauses by normal monolingual children during normal development, healthy young adults, healthy aging adults, and aging adults diagnosed with mild cognitive impairment, a recognized potential harbinger of Alzheimer's disease. Our results refute the regression hypothesis in this area and lead to potential syntactic markers for prodromal Alzheimer's disease and predictions for future brain imaging analyses. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lust, Barbara; Henderson, Charles R., Jr.; Whitlock, Jordan; Costigan, Aileen; Immerman, Alex] Cornell Univ, Coll Human Ecol, Ithaca, NY 14850 USA. [Flynn, Suzanne] MIT, Dept Linguist & Philosophy, Cambridge, MA 02139 USA. [Sherman, Janet Cohen; Mancuso, Sarah] Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. [Gair, James] Cornell Univ, Dept Linguist, Ithaca, NY 14850 USA. [Cordella, Claire] Harvard Univ, Cambridge, MA 02138 USA. [Chen, Zhong] Rochester Inst Technol, Dept Modern Languages & Cultures, Rochester, NY 14623 USA. RP Lust, B (reprint author), Cornell Univ, Coll Human Ecol, G57,Martha Van Rensselaer Hall, Ithaca, NY 14850 USA. EM bc14@cornell.edu; sflynn@mit.edu FU National Institute of Aging [P50 AG005134]; Hatch Grant/Federal Formula Funds [NIFA NYC-321420]; Cornell Bronfenbrenner Center for Life Course Development; Cornell Institute for Translational Research on Aging; Cornell University Institute for Social Sciences FX We thank Dr. Bradley Hyman, Liang Yap and Jeanette Gunther of the Massachusetts General Hospital Massachusetts Alzheimer's Disease Research Center, and National Institutes of Health and the National Institute of Aging (Grant No. P50 AG005134) for provision of our replication MCI group reported in this paper. We thank Jean Berko Gleason for discussion of the regression hypothesis and knowledge of its initial proposal by Roman Jakobson, and Lisa Menn and Sheila Blumstein for discussion. We thank Marc Harrison for insight regarding neuroscientific implications of our results, Leah Shabo, Colleen Sullivan, Jenna Behrendt, Irina Potapova, Ali O'Neill, Annie Bass, Alexander Botkin, Jenn Kim, Sylvan Whitmore, Michael Schramm, Helen Tian, Katie Lim, Sue Song, Jenn Ditzell, and Casey Evans for assistance in data transcription, analysis, and discussion, and Diane Rak for data-collection assistance at MIT. We thank Barbara Ganzel for information on the neurobiological instantiations of the regression hypothesis and Nathan Spreng for discussion of the neuroscientific implications of our results. This research was supported by Hatch Grant/Federal Formula Funds [Grant No. NIFA NYC-321420], Cornell Bronfenbrenner Center for Life Course Development seed grant, Cornell Institute for Translational Research on Aging pilot study program, and a Cornell University Institute for Social Sciences seed grant. No funder had a role in the study design, the collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the article for publication. NR 81 TC 0 Z9 0 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD APR PY 2015 VL 143 BP 1 EP 10 DI 10.1016/j.bandl.2015.01.013 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA CF6IE UT WOS:000352659600001 PM 25707009 ER PT J AU Gardner, A Iverson, GL Levi, CR Schofield, PW Kay-Lambkin, F Kohler, RMN Stanwell, P AF Gardner, Andrew Iverson, Grant L. Levi, Christopher R. Schofield, Peter W. Kay-Lambkin, Frances Kohler, Ryan M. N. Stanwell, Peter TI A systematic review of concussion in rugby league SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Review DE Concussion; Rugby ID SPORTS-RELATED CONCUSSION; SCHOOL FOOTBALL PLAYERS; TRAUMATIC BRAIN-INJURY; MILD HEAD-INJURY; NEW-ZEALAND; INTERNATIONAL-CONFERENCE; RISK-FACTORS; ICE HOCKEY; IMPACT; RATES AB Objectives Concussion remains one of the inherent risks of participation in rugby league. While other injuries incurred by rugby league players have been well studied, less focus and attention has been directed towards concussion. Review method The current review examined all articles published in English from 1900 up to June 2013 pertaining to concussion in rugby league players. Data sources Publications were retrieved via six databases using the key search terms: rugby league, league, football; in combination with injury terms: athletic injuries, concussion, sports concussion, sports-related concussion, brain concussion, brain injury, brain injuries, mild traumatic brain injury, mTBI, traumatic brain injury, TBI, craniocerebral trauma, head injury and brain damage. Observational, cohort, correlational, cross-sectional and longitudinal studies were all included. Results 199 rugby league injury publications were identified. 39 (20%) were related in some way to concussion. Of the 39 identified articles, 6 (15%) had the main aim of evaluating concussion, while the other 33 reported on concussion incidence as part of overall injury data analyses. Rugby league concussion incidence rates vary widely from 0.0 to 40.0/1000 playing hours, depending on the definition of injury (time loss vs no time loss). The incidence rates vary across match play versus training session, seasons (winter vs summer) and playing position (forwards vs backs). The ball carrier has been found to be at greater risk for injury than tacklers. Concussion accounts for 29% of all injuries associated with illegal play, but only 9% of injuries sustained in legal play. Conclusions In comparison with other collision sports, research evaluating concussion in rugby league is limited. With such limited published rugby league data, there are many aspects of concussion that require attention, and future research may be directed towards these unanswered questions. C1 [Gardner, Andrew; Levi, Christopher R.; Schofield, Peter W.; Kay-Lambkin, Frances] Univ Newcastle, Sch Med & Publ Hlth, Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Kay-Lambkin, Frances] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia. [Kohler, Ryan M. N.] Australian Sports Commiss, Canberra, ACT, Australia. [Stanwell, Peter] Univ Newcastle, Sch Hlth Sci, Fac Hlth & Med, Callaghan, NSW 2308, Australia. RP Gardner, A (reprint author), Calvary Mater Hosp, Ctr Translat Neurosci & Mental Hlth, Level 5,McAuley Bldg, Waratah, NSW 2298, Australia. EM andrew.gardner@neurogard.com.au RI Gardner, Andrew/J-5162-2013; Stanwell, Peter/F-9136-2012; OI Kay-Lambkin, Frances/0000-0002-4252-5572; Stanwell, Peter/0000-0002-4780-0393 FU Australian Football League (AFL); NSW Sporting Injuries Committee; Brain Foundation; Hunter Medical Research Institute; ImPACT Applications, Inc; CNS Vital Signs; Psychological Assessment Resources (PAR, Inc); Canadian Institute of Health Research; Alcohol Beverage Medical Research Council; Rehabilitation Research and Development (RR&D) Service of the US Department of Veterans Affairs; Vancouver Coastal Health Research Institute; Roche Diagnostics Canada FX AG has a clinical practice in neuropsychology involving individuals who have sustained sports-related concussion (including current and former athletes). He has received travel funding from the Australian Football League (AFL) to present at the Concussion in Football Conference in 2013. Previous grant funding includes the NSW Sporting Injuries Committee, the Brain Foundation and the Hunter Medical Research Institute, supported by Jennie Thomas. GLI has been reimbursed by the government, professional scientific bodies and commercial organisations for discussing or presenting research relating to mild traumatic brain injury (TBI) and sport-related concussion at meetings, scientific conferences and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs. He has received research funding from several test publishing companies, including ImPACT Applications, Inc, CNS Vital Signs and Psychological Assessment Resources (PAR, Inc). He is a coinvestigator, collaborator or consultant on grants relating to mild TBI funded by several organisations, including, but not limited to, the Canadian Institute of Health Research, Alcohol Beverage Medical Research Council, Rehabilitation Research and Development (RR&D) Service of the US Department of Veterans Affairs, Vancouver Coastal Health Research Institute and Roche Diagnostics Canada. NR 75 TC 8 Z9 8 U1 4 U2 18 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD APR PY 2015 VL 49 IS 8 BP 495 EP 499 DI 10.1136/bjsports-2013-093102 PG 5 WC Sport Sciences SC Sport Sciences GA CF4OI UT WOS:000352529000004 PM 24723636 ER PT J AU Rossi, ED Pusztaszeri, M Schmitt, F Bongiovanni, M Chandra, A Faquin, WC AF Rossi, Esther Diana Pusztaszeri, Marc Schmitt, Fernando Bongiovanni, Massimo Chandra, Ashish Faquin, William C. TI Thyroid FNA: International Perspectives From the European Congress of Cytopathology-Can We Cross the Bridge of Classifications? SO CANCER CYTOPATHOLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; FOLLICULAR-PATTERNED LESIONS; BETHESDA SYSTEM; DIAGNOSTIC-ACCURACY; CYTOLOGY; NODULES; IMMUNOCYTOCHEMISTRY; TERMINOLOGY; MANAGEMENT; NEOPLASMS AB The 38th European Congress of Cytology 2014, held in Geneva, Switzerland, offered a specific symposium concerning the Bethesda thyroid classification scheme. What emerged in that thyroid symposium, which was attended by all of the authors of this commentary, was the persistent need for a universally adopted thyroid fine-needle aspiration reporting system that can diagnose the same thyroid nodule in the same way anywhere in the world. Herein, the authors critically outline the advantages and limits of thyroid fine-needle aspiration classification schemes that were discussed at the symposium. C1 [Rossi, Esther Diana] Univ Cattolica Sacro Cuore, Agostino Gemelli Sch Med, Div Anat Pathol & Histol, I-00168 Rome, Italy. [Pusztaszeri, Marc] Univ Hosp Geneva, Div Clin Pathol, Geneva, Switzerland. [Schmitt, Fernando] Univ Porto, Inst Mol Pathol & Immunol, P-4100 Oporto, Portugal. [Schmitt, Fernando] Natl Hlth Lab, Luxembourg, Luxembourg. [Bongiovanni, Massimo] Univ Lausanne Hosp, Inst Pathol, Lausanne, Switzerland. [Chandra, Ashish] St Thomas Hosp, Dept Cellular Pathol, London, England. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rossi, ED (reprint author), Univ Cattolica Sacro Cuore, Agostino Gemelli Sch Med, Div Anat Pathol & Histol, Largo Francesco Vito 1, I-00168 Rome, Italy. EM esther.rossi@rm.unicatt.it RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 22 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR PY 2015 VL 123 IS 4 BP 207 EP 211 DI 10.1002/cncy.21517 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA CG1SW UT WOS:000353055300003 PM 25641880 ER PT J AU Ahronian, LG Sennott, EM Van Allen, EM Wagle, N Kwak, EL Faris, JE Godfrey, JT Nishimura, K Lynch, KD Mermel, CH Lockerman, EL Kalsy, A Gurski, JM Bahl, S Anderka, K Green, LM Lennon, NJ Huynh, TG Mino-Kenudson, M Getz, G Dias-Santagata, D Iafrate, AJ Engelman, JA Garraway, LA Corcoran, RB AF Ahronian, Leanne G. Sennott, Erin M. Van Allen, Eliezer M. Wagle, Nikhil Kwak, Eunice L. Faris, Jason E. Godfrey, Jason T. Nishimura, Koki Lynch, Kerry D. Mermel, Craig H. Lockerman, Elizabeth L. Kalsy, Anuj Gurski, Joseph M., Jr. Bahl, Samira Anderka, Kristin Green, Lisa M. Lennon, Niall J. Huynh, Tiffany G. Mino-Kenudson, Mari Getz, Gad Dias-Santagata, Dora Iafrate, A. John Engelman, Jeffrey A. Garraway, Levi A. Corcoran, Ryan B. TI Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations SO CANCER DISCOVERY LA English DT Article ID MEK INHIBITORS; METASTATIC MELANOMA; AMPLIFICATION; MUTATIONS; EGFR; THERAPY; CELLS; GENE; KRAS AB BRAF mutations occur in approximately 10% of colorectal cancers. Although RAF inhibitor monotherapy is highly effective in BRAF-mutant melanoma, response rates in BRAF-mutant colorectal cancer are poor. Recent clinical trials of combined RAF/EGFR or RAF/MEK inhibition have produced improved efficacy, but patients ultimately develop resistance. To identify molecular alterations driving clinical acquired resistance, we performed whole-exome sequencing on paired pretreatment and postprogression tumor biopsies from patients with BRAF-mutant colorectal cancer treated with RAF inhibitor combinations. We identified alterations in MAPK pathway genes in resistant tumors not present in matched pretreatment tumors, including KRAS amplification, BRAF amplification, and a MEK1 mutation. These alterations conferred resistance to RAF/EGFR or RAF/MEK combinations through sustained MAPK pathway activity, but an ERK inhibitor could suppress MAPK activity and overcome resistance. Identification of MAPK pathway reactivating alterations upon clinical acquired resistance underscores the MAPK pathway as a critical target in BRAF-mutant colorectal cancer and suggests therapeutic options to overcome resistance. SIGNIFICANCE: RAF inhibitor combinations represent promising approaches in clinical development for BRAF-mutant colorectal cancer. Initial characterization of clinical acquired resistance mechanisms to these regimens identified several MAPK pathway alterations driving resistance by reactivating MAPK signaling, highlighting the critical dependence of BRAF-mutant colorectal cancers on MAPK signaling and offering potential strategies to overcome resistance. (C)2015 AACR. C1 [Ahronian, Leanne G.; Sennott, Erin M.; Kwak, Eunice L.; Faris, Jason E.; Godfrey, Jason T.; Nishimura, Koki; Mermel, Craig H.; Lockerman, Elizabeth L.; Kalsy, Anuj; Gurski, Joseph M., Jr.; Getz, Gad; Engelman, Jeffrey A.; Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Ahronian, Leanne G.; Sennott, Erin M.; Kwak, Eunice L.; Faris, Jason E.; Gurski, Joseph M., Jr.; Engelman, Jeffrey A.; Corcoran, Ryan B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Van Allen, Eliezer M.; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Van Allen, Eliezer M.; Wagle, Nikhil; Mermel, Craig H.; Bahl, Samira; Anderka, Kristin; Green, Lisa M.; Lennon, Niall J.; Getz, Gad; Garraway, Levi A.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Lynch, Kerry D.; Huynh, Tiffany G.; Mino-Kenudson, Mari; Dias-Santagata, Dora; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Lynch, Kerry D.; Huynh, Tiffany G.; Mino-Kenudson, Mari; Dias-Santagata, Dora; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA USA. RP Corcoran, RB (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th Floor, Boston, MA 02129 USA. EM rbcorcoran@partners.org FU NIH Gastrointestinal Cancer [SPORE P50 CA127003]; Damon Runyon Clinical Investigator Award [1K08CA166510]; National Human Genome Research Institute [U54HG003067] FX This study is supported by grants from the NIH Gastrointestinal Cancer SPORE P50 CA127003 (to R.B. Corcoran, L.A. Garraway, J.A. Engelman, and E.M. Sennott), a Damon Runyon Clinical Investigator Award and 1K08CA166510 (to R.B. Corcoran), and National Human Genome Research Institute grant U54HG003067. NR 25 TC 57 Z9 57 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2015 VL 5 IS 4 BP 358 EP 367 DI 10.1158/2159-8290.CD-14-1518 PG 10 WC Oncology SC Oncology GA CF2JJ UT WOS:000352373300023 PM 25673644 ER PT J AU Stegeman, S Amankwah, E Klein, K O'Mara, TA Kim, D Lin, HY Permuth-Wey, J Sellers, TA Srinivasan, S Eeles, R Easton, D Kote-Jarai, Z Al Olama, AA Benlloch, S Muir, K Giles, GG Wiklund, F Gronberg, H Haiman, CA Schleutker, J Nordestgaard, BG Travis, RC Neal, D Pharoah, P Khaw, KT Stanford, JL Blot, WJ Thibodeau, S Maier, C Kibel, AS Cybulski, C Cannon-Albright, L Brenner, H Kaneva, R Teixeira, MR Spurdle, AB Clements, JA Park, JY Batra, J AF Stegeman, Shane Amankwah, Ernest Klein, Kerenaftali O'Mara, Tracy A. Kim, Donghwa Lin, Hui-Yi Permuth-Wey, Jennifer Sellers, Thomas A. Srinivasan, Srilakshmi Eeles, Rosalind Easton, Doug Kote-Jarai, Zsofia Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Giles, Graham G. Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A. Schleutker, Johanna Nordestgaard, Borge G. Travis, Ruth C. Neal, David Pharoah, Paul Khaw, Kay-Tee Stanford, Janet L. Blot, William J. Thibodeau, Stephen Maier, Christiane Kibel, Adam S. Cybulski, Cezary Cannon-Albright, Lisa Brenner, Hermann Kaneva, Radka Teixeira, Manuel R. Spurdle, Amanda B. Clements, Judith A. Park, Jong Y. Batra, Jyotsna CA PRACTICAL Consortium Australian Prostate Canc TI A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer SO CANCER DISCOVERY LA English DT Article ID SUSCEPTIBILITY LOCI; MICRORNA EXPRESSION; ANTIANGIOGENIC ACTIVITY; DUAL ROLE; ANTIGEN; VAMP8; IDENTIFICATION; RISK; TOOL; TRANSLATION AB Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3' untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P < 2.3 x 10(-5)) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. SIGNIFICANCE: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. (C)2015 AACR. C1 [Stegeman, Shane; Srinivasan, Srilakshmi; Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr Qld, Brisbane, Qld 4059, Australia. [Stegeman, Shane; Srinivasan, Srilakshmi; Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Translat Res Inst, Sch Biomed Sci, Brisbane, Qld 4059, Australia. [Amankwah, Ernest; Permuth-Wey, Jennifer; Sellers, Thomas A.; Park, Jong Y.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA. [Klein, Kerenaftali] QIMR Berghofer Med Res Inst, Stat Unit, Brisbane, Qld, Australia. [O'Mara, Tracy A.; Spurdle, Amanda B.] QIMR Berghofer Med Res Inst, Genet & Computat Biol Div, Mol Canc Epidemiol Lab, Brisbane, Qld, Australia. [Kim, Donghwa] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Mol Oncol, Tampa, FL 33682 USA. [Lin, Hui-Yi; PRACTICAL Consortium] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat & Bioinformat, Tampa, FL 33682 USA. [Eeles, Rosalind; Kote-Jarai, Zsofia] Inst Canc Res, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Fulham, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Al Olama, Ali Amin; Benlloch, Sara] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England. [Muir, Kenneth] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland. [Schleutker, Johanna] Univ Tampere, BioMediTech, Inst Biomed Technol, FIN-33101 Tampere, Finland. [Schleutker, Johanna] FimLab Labs, Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Neal, David] Univ Cambridge, Addenbrookes Hosp, Surg Oncol Urooncol S4, Cambridge CB2 2QQ, England. [Neal, David] Canc Res UK, Cambridge Res Inst, Cambridge, England. [Pharoah, Paul] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England. [Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Cambridge, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [Thibodeau, Stephen] Mayo Clin, Rochester, MN USA. [Maier, Christiane] Univ Hosp Ulm, Dept Urol, Ulm, Germany. [Maier, Christiane] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kibel, Adam S.] Washington Univ, St Louis, MO USA. [Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Kaneva, Radka] Med Univ Sofia, Mol Med Ctr, Sofia, Bulgaria. [Kaneva, Radka] Med Univ Sofia, Dept Med Chem & Biochem, Sofia, Bulgaria. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal. RP Batra, J (reprint author), Queensland Univ Technol, Translat Res Inst, 37 Kent St, Brisbane, Qld 4059, Australia. EM jyotsna.batra@qut.edu.au RI Risbridger, Gail/B-8655-2008; Paulo, Paula/F-1441-2016; Teixeira, Manuel/E-4885-2011; Batra, Jyotsna/B-4130-2011; O'Mara, Tracy/M-7508-2016; Henrique, Rui/I-2757-2013; Brenner, Hermann/B-4627-2017; OI Risbridger, Gail/0000-0003-3089-4028; Clements, Judith/0000-0001-6026-1964; Paulo, Paula/0000-0001-8387-2127; Teixeira, Manuel/0000-0002-4896-5982; O'Mara, Tracy/0000-0002-5436-3232; Henrique, Rui/0000-0003-3171-4666; Brenner, Hermann/0000-0002-6129-1572; Eeles, Rosalind/0000-0002-3698-6241 FU National Health and Medical Research Council (NHMRC) Career Development Fellowship; Cure Cancer Australia Foundation and Cancer Australia PdCCRS [1068321]; NHMRC [1050742, 614296]; Department of Defense [W81XWH-12-1-0113]; NCI [R01CA128813]; Cancer Prevention Fellowship from the NCI [R25T CA147832]; Prostate Cancer Foundation of Australia; Canadian Institutes of Health Research; European Commission's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK (CRUK) [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]; NIH Cancer PostCancer GWAS initiative grant [1 U19 CA 148537-01]; NIHR; Royal Marsden NHS Foundation Trust; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund FX J. Batra was supported by a National Health and Medical Research Council (NHMRC) Career Development Fellowship. A.B. Spurdle is an NHMRC Senior Research Fellow. J.A. Clements is an NHMRC Principal Research Fellow. This work was supported by Cure Cancer Australia Foundation and Cancer Australia PdCCRS grant 1068321 and NHMRC grant 1050742 (Principal Investigator, J. Batra); Department of Defense grant W81XWH-12-1-0113 (Principal Investigator, J.Y. Park); and NCI R01CA128813 (Principal Investigator, J.Y. Park). E.K. Amankwah was supported by a Cancer Prevention Fellowship from the NCI (R25T CA147832) while this study was conducted. The Australian Prostate Cancer BioResource (APCB) funding was obtained from the NHMRC (enabling grant 614296) and an infrastructure grant from the Prostate Cancer Foundation of Australia.; This work was supported by the Canadian Institutes of Health Research; European Commission's Seventh Framework Programme grant agreement no223175 (HEALTH-F2-2009-223175); Cancer Research UK (CRUK) grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135; and NIH Cancer PostCancer GWAS initiative grant no. 1 U19 CA 148537-01 (the GAME-ON initiative). The authors acknowledge support from the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust.; Funding for the iCOGS infrastructure came from the European Commission's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175); Cancer Research UK grants C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, and C5047/A10692; NIH CA128978; and the Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112--the GAME-ON initiative). This study was also supported by the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. NR 50 TC 8 Z9 10 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2015 VL 5 IS 4 BP 368 EP 379 DI 10.1158/2159-8290.CD-14-1057 PG 12 WC Oncology SC Oncology GA CF2JJ UT WOS:000352373300024 PM 25691096 ER PT J AU Bostic, JQ Nevarez, MD Potter, MP Prince, JB Benningfield, MM Aguirre, BA AF Bostic, Jeff Q. Nevarez, Michael D. Potter, Mona P. Prince, Jefferson B. Benningfield, Margaret M. Aguirre, Blaise A. TI Being Present at School: Implementing Mindfulness in Schools SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Mindfulness; Schools; Students; Meditation ID STRESS REDUCTION; CONTROLLED-TRIAL; SUBSTANCE-ABUSE; ADOLESCENTS; INTERVENTIONS; METAANALYSIS; FEASIBILITY; CHILDREN; PROGRAM; BURNOUT AB Developmentally sensitive efforts to help students learn, practice, and regularly use mindfulness tactics easily and readily in and beyond the classroom are important to help them manage future stresses. Mindfulness emphasizes consciously focusing the mind in the present moment, purposefully, without judgment or attachment. Meditation extends this to setting aside time and places to practice mindfulness, and additionally, yoga includes physical postures and breathing techniques that enhance mindfulness and meditation. Several mindfulness programs and techniques have been applied in schools, with positive benefits reported. Some elements of these programs require modifications to be sensitive to the developmental state of the children receiving mindfulness training. C1 [Bostic, Jeff Q.; Nevarez, Michael D.; Prince, Jefferson B.; Aguirre, Blaise A.] Massachusetts Gen Hosp, Child Psychiat, Boston, MA 02114 USA. [Potter, Mona P.] Harvard Univ, Sch Med, McLean Psychiat Hosp, Boston, MA USA. [Benningfield, Margaret M.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37212 USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, Child Psychiat, Yawkey 6,55 Parkman St, Boston, MA 02114 USA. EM jbostic@partners.org NR 47 TC 1 Z9 1 U1 17 U2 84 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 EI 1558-0490 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2015 VL 24 IS 2 BP 245 EP + DI 10.1016/j.chc.2014.11.010 PG 16 WC Psychiatry SC Psychiatry GA CF6IT UT WOS:000352661100004 PM 25773322 ER PT J AU Benningfield, MM Potter, MP Bostic, JQ AF Benningfield, Margaret M. Potter, Mona P. Bostic, Jeff Q. TI Educational Impacts of the Social and Emotional Brain SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Neuroscience; Cognitive; Emotional; Education; Students ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NEGATIVITY BIAS; RISK-TAKING; ADOLESCENCE; NEUROSCIENCE; NEUROCIRCUITRY; MATURATION; CHILDHOOD; COGNITION; AMYGDALA AB Advances in neuroscience related to social and emotional development have significant implications for educational practice. The human brain cannot fully dissociate cognitive from emotional events, and therefore educational programming that recognizes the importance of social-emotional development also facilitates academic achievement. The ideal learning environment encourages the development of social-emotional and academic neuronal pathways. Taking advantage of the emerging understanding of the developing brain offers opportunities to facilitate greater academic gains. C1 [Benningfield, Margaret M.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37212 USA. [Potter, Mona P.] Harvard Univ, Sch Med, McLean Psychiat Hosp, Boston, MA USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Child Psychiat, Boston, MA 02114 USA. RP Benningfield, MM (reprint author), Vanderbilt Univ, Dept Psychiat, 1601 23rd Ave South,3068C, Nashville, TN 37212 USA. EM meg.benningfield@Vanderbilt.Edu NR 41 TC 0 Z9 0 U1 2 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 EI 1558-0490 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2015 VL 24 IS 2 BP 261 EP + DI 10.1016/j.chc.2014.12.001 PG 16 WC Psychiatry SC Psychiatry GA CF6IT UT WOS:000352661100005 PM 25773323 ER PT J AU Bhan, I Dobens, D Tamez, H Deferio, JJ Li, YC Warren, HS Ankers, E Wenger, J Tucker, JK Trottier, C Pathan, F Kalim, S Nigwekar, SU Thadhani, R AF Bhan, Ishir Dobens, Dorothy Tamez, Hector Deferio, Joseph J. Li, Yan Chun Warren, H. Shaw Ankers, Elizabeth Wenger, Julia Tucker, J. Kevin Trottier, Caitlin Pathan, Fridosh Kalim, Sahir Nigwekar, Sagar U. Thadhani, Ravi TI Nutritional Vitamin D Supplementation in Dialysis: A Randomized Trial SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; INCIDENT HEMODIALYSIS-PATIENTS; D-BINDING PROTEIN; D DEFICIENCY; CHOLECALCIFEROL SUPPLEMENTATION; SECONDARY HYPERPARATHYROIDISM; CLINICAL POPULATIONS; 25-HYDROXYVITAMIN D; MINERAL METABOLISM; ERGOCALCIFEROL AB Background and objectives Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency is common in patients initiating long-term hemodialysis, but the safety and efficacy of nutritional vitamin D supplementation in this population remain uncertain. Design, setting, participants, & measurements This randomized, placebo-controlled, parallel-group multicenter trial compared two doses of ergocalciferol with placebo between October 2009 and March 2013. Hemodialysis patients (n=105) with 25(OH)D levels <= 32 ng/ml from 32 centers in the Northeast United States were randomly assigned to oral ergocalciferol, 50,000 IU weekly (n=36) or monthly (n=33), or placebo (n=36) for a 12-week treatment period. The primary endpoint was the achievement of vitamin D sufficiency (25[OH]D >32 ng/ml) at the end of the 12-week treatment period. Survival was assessed through 1 year. Results Baseline characteristics were similar across all arms, with overall mean +/- SD 25(OH)D levels of 21.9 +/- 6.9 ng/ml. At 12 weeks, vitamin D sufficiency (25[OH]D >32 ng/ml) was achieved in 91% (weekly), 66% (monthly), and 35% (placebo) (P<0.001). Mean 25(OH)D was significantly higher in both the weekly (49.8 +/- 2.3 ng/ml; P<0.001) and monthly (38.3 +/- 2.4 ng/ml; P=0.001) arms compared with placebo (27.4 +/- 2.3 ng/ml). Calcium, phosphate, parathyroid hormone levels, and active vitamin D treatment did not differ between groups. All-cause and cause-specific hospitalizations and adverse events were similar between groups during the intervention period. Lower all-cause mortality among ergocalciferol-treated participants was not, statistically significant (hazard ratio, 0.28; 95% confidence interval, 0.07 to 1.19). Conclusions Oral ergocalciferol can increase 25 (OH)D levels in incident hemodialysis patients without significant alterations in blood calcium, phosphate, or parathyroid hormone during a. 12-week period. C1 [Bhan, Ishir; Dobens, Dorothy; Tamez, Hector; Deferio, Joseph J.; Ankers, Elizabeth; Wenger, Julia; Tucker, J. Kevin; Trottier, Caitlin; Kalim, Sahir; Nigwekar, Sagar U.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, Boston, MA 02114 USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. [Pathan, Fridosh] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. RP Bhan, I (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,Suite 750, Boston, MA 02114 USA. EM ibhan@mgh.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5K23-DK081677]; NIDDK [1R01-DK084974, K24-DK094872, 5R01-DK092143] FX I.B. was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (5K23-DK081677). R.T. was supported by grants from the NIDDK (1R01-DK084974, K24-DK094872). The study was sponsored by a grant from the NIDDK (5R01-DK092143). NR 43 TC 20 Z9 20 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR PY 2015 VL 10 IS 4 BP 611 EP 619 DI 10.2215/CJN.06910714 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CF3QK UT WOS:000352463400012 PM 25770176 ER PT J AU Scontras, G Badecker, W Shank, L Lim, E Fedorenko, E AF Scontras, Gregory Badecker, William Shank, Lisa Lim, Eunice Fedorenko, Evelina TI Syntactic Complexity Effects in Sentence Production SO COGNITIVE SCIENCE LA English DT Article DE Syntactic complexity; Sentence production; Sentence processing; Working memory; Relative clauses; Wh-questions ID OBJECT RELATIVE CLAUSES; WORKING-MEMORY; MESSAGE FORMULATION; LANGUAGE PRODUCTION; DEPENDENCY LENGTH; COMPREHENSION; FREQUENCY; ENGLISH; RETRIEVAL; SPEAKING AB Syntactic complexity effects have been investigated extensively with respect to comprehension (e.g., Demberg & Keller, 2008; Gibson, 1998, 2000; Gordon etal., 2001, 2004; Grodner & Gibson, 2005; King & Just, 1991; Lewis & Vasishth, 2005; Lewis etal., 2006; McElree etal., 2003; Wanner & Maratsos, 1978). According to one prominent class of accounts (experience-based accounts; e.g., Hale, 2001; Levy, 2008; Gennari & MacDonald, 2008, 2009; Wells etal., 2009), certain structures cause comprehension difficulty due to their scarcity in the language. But why are some structures less frequent than others? In two elicited-production experiments we investigated syntactic complexity effects in relative clauses (Experiment 1) and wh-questions (Experiment 2) varying in whether or not they contained non-local dependencies. In both experiments, we found reliable durational differences between subject-extracted structures (which only contain local dependencies) and object-extracted structures (which contain nonlocal dependencies): Participants took longer to begin and produce object-extractions. Furthermore, participants were more likely to be disfluent in the object-extracted constructions. These results suggest that there is a cost associated with planning and uttering the more syntactically complex, object-extracted structures, and that this cost manifests in the form of longer durations and disfluencies. Although the precise nature of this cost remains to be determined, these effects provide one plausible explanation for the relative rarity of object-extractions: They are more costly to produce. C1 [Scontras, Gregory] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Badecker, William] Univ Arizona, Cognit Sci Program, Tucson, AZ 85721 USA. [Shank, Lisa] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Lim, Eunice] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA. [Fedorenko, Evelina] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Scontras, G (reprint author), Stanford Univ, Dept Psychol, 450 Serra Mall, Stanford, CA 94305 USA. EM scontras@stanford.edu; evelina9@mit.edu OI Shank, Lisa/0000-0002-6922-7946 FU Eunice Kennedy Shriver NICHD K99 award [HD-057522] FX We would like to thank several research assistants for help in setting up the experiments, and collecting and coding the data: Teresa Giblin, Diane Lo, Nicki Longe, and Alison Park. We thank Wade Shen (Lincoln Labs) for help with the forced alignment procedure, and Michael Wagner (McGill University) for providing the Praat script for extracting the acoustic features. We also thank Steve Piantadosi (University of Rochester) for help with the Praat script and Peter Graff (Intel Corporation) for help with the statistical analyses. We are grateful to the audience at CUNY 2007, TedLab members, Roger Levy, and Maria Polinsky for helpful comments. Finally, Ted Gibson deserves very special thanks for his help with all stages of the project and for his comments on the manuscript. The material in this paper is based in part on work done while the second author was serving as an NSF Program Director. Any opinions, findings, and conclusions expressed in this paper are those of the authors and do not necessarily reflect the views of the U.S. National Science Foundation. EF was supported by the Eunice Kennedy Shriver NICHD K99 award HD-057522. NR 70 TC 5 Z9 5 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-0213 EI 1551-6709 J9 COGNITIVE SCI JI Cogn. Sci. PD APR PY 2015 VL 39 IS 3 BP 559 EP 583 DI 10.1111/cogs.12168 PG 25 WC Psychology, Experimental SC Psychology GA CF8FX UT WOS:000352792700004 PM 25256303 ER PT J AU Janjua, SA Hoffmann, U AF Janjua, Sumbal A. Hoffmann, Udo TI New Insights from Major Prospective Cohort Studies with Cardiac CT SO CURRENT CARDIOLOGY REPORTS LA English DT Article DE Cardiac computed tomography; Coronary artery disease; Coronary artery calcification score; Chest pain; Symptomatic; Asymptomatic ID CORONARY-ARTERY-DISEASE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACUTE CHEST-PAIN; AMERICAN-HEART-ASSOCIATION; FRACTIONAL FLOW RESERVE; ALL-CAUSE MORTALITY; PROGNOSTIC VALUE; DIAGNOSTIC PERFORMANCE; TASK-FORCE; MYOCARDIAL-INFARCTION AB Each year, 11 million patients present in the USA with new symptoms suggestive of obstructive coronary artery disease (CAD). Most undergo stress testing but < 10 % demonstrate myocardial ischemia. Moreover, up to 60% will have CAD which adversely affects outcomes. Cardiac computed tomography (CCT) is being used increasingly as an alternative to stress testing to rule out obstructive CAD in symptomatic patients, and large cohort studies in asymptomatic patients have identified burden of coronary atherosclerosis as a predictor of major adverse cardiovascular events (MACE). This review article will critically evaluate major clinical studies on the use of CCT in both symptomatic and asymptomatic patients and discuss the lessons for the clinical use of CCT. C1 [Janjua, Sumbal A.; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiac CT PET MR, Dept Radiol, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Div Cardiac CT PET MR, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM sjanjua@partners.org; uhoffmann@mgh.harvard.edu FU NIH/NHLBI FX Udo Hoffmann has received grant support from NIH/NHLBI. NR 42 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD APR PY 2015 VL 17 IS 4 AR 19 DI 10.1007/s11886-015-0571-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF8NX UT WOS:000352819900004 PM 25725603 ER PT J AU Yeh, DD King, ME AF Yeh, Doreen DeFaria King, Mary Etta TI Congenital Heart Disease in the Adult: What Should the Adult Cardiologist Know? SO CURRENT CARDIOLOGY REPORTS LA English DT Article DE Echocardiography; Adult congenital heart disease; Pregnancy; heart disease ID CARDIOVASCULAR MAGNETIC-RESONANCE; BICUSPID AORTIC-VALVE; CORRECTED TRANSPOSITION; GREAT-ARTERIES; ATRIOVENTRICULAR DISCORDANCE; INFECTIVE ENDOCARDITIS; REPAIRED TETRALOGY; AMERICAN SOCIETY; TASK-FORCE; FALLOT AB There is an increasing population of adults with congenital heart disease (CHD) due to successful pediatric medical and surgical intervention, and commensurate with this increase is a rise in heart failure, hospital admissions, and hospital costs among adult CHD patients. This group of patients requires careful long-term evaluation and follow-up of the residua and sequelae of their cardiac anomalies that arise in adulthood to prevent late complications. This article addresses congenital heart defects that are encountered in a general adult cardiology practice and reviews clinical, anatomic, and imaging features of each lesion, fundamental management issues, indications for interventions (and often reinterventions), issues related to endocarditis prophylaxis, pregnancy, and appropriateness of referral to a dedicated adult CHD program for long-term care. C1 [Yeh, Doreen DeFaria] Massachusetts Gen Hosp, Echocardiog Sect, Adult Congenital Heart Dis Program, Div Cardiol, Boston, MA 02114 USA. [King, Mary Etta] Massachusetts Gen Hosp Children, Cardiac Ultrasound Lab, Div Pediat Cardiol, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Massachusetts Gen Hosp, Echocardiog Sect, Adult Congenital Heart Dis Program, Div Cardiol, 55 Fruit St,Yawkey 5-700, Boston, MA 02114 USA. EM ddefariayeh@mgh.harvard.edu; mking3@partners.org NR 48 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD APR PY 2015 VL 17 IS 4 AR 25 DI 10.1007/s11886-015-0579-7 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF8NX UT WOS:000352819900010 ER PT J AU Agaku, IT Obadan, EM Odukoya, OO Olufajo, O AF Agaku, Israel T. Obadan, Enihomo M. Odukoya, Oluwakemi O. Olufajo, Olubode TI Tobacco-free schools as a core component of youth tobacco prevention programs: a secondary analysis of data from 43 countries SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SMOKING; TRIAL; INTERVENTION AB Background: Preventing tobacco use is a key aspect of health promotion during adolescence. We assessed prevalence and impact of school-based tobacco prevention programs in 43 countries. Methods: We performed a secondary analysis of national data of students aged 13-15 years (Global Youth Tobacco Surveys) from 43 countries during 2005-2011. National surveys of the corresponding school personnel (Global School Personnel Surveys) were performed in each country during the same year as the student surveys. Data on status of enforcement of national smoke-free school policies were obtained from the 2008 and 2009 WHO MPOWER reports. Logistic regression was used to measure ecologic-level associations between school-based tobacco prevention programs and tobacco-related knowledge and behaviour among students (P < 0.05). Results: The proportion of students who were taught in class about the dangers of tobacco use during the school year ranged from 31.4% (Georgia) to 83.4% (Papua New Guinea). For every 10% increase (country level) in the proportion of teachers who reported having a tobacco prevention curriculum in their school, the odds of students reporting exposure to education in class about the dangers of tobacco increased by 6.0% (AOR = 1.06; 95% CI: 1.04-1.08). However, didactic education in class about the dangers of tobacco use was not independently associated with student current cigarette smoking behavior. Conversely, the likelihood of being a current smoker was significantly lower among students in countries with moderate/strongly enforced national smoke-free school policies compared with those in countries with poorly enforced/no national smoke-free school policies (AOR = 0.59; 95% CI: 0.45-0.76). Conclusions: Comprehensive tobacco prevention programs that include well-enforced smoke-free school policies may help reduce youth smoking. C1 [Agaku, Israel T.] Harvard Univ, Sch Publ Hlth, Ctr Global Tobacco Control, Dept Social & Behav Sci, Boston, MA 02115 USA. [Obadan, Enihomo M.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. [Odukoya, Oluwakemi O.] Univ Lagos, Coll Med, Dept Community Hlth & Primary Care, Idi Araba, Lagos State, Nigeria. [Olufajo, Olubode] Harvard Univ, Sch Dent Med, Dept Epidemiol, Boston, MA 02115 USA. [Olufajo, Olubode] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Agaku, IT (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Global Tobacco Control, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM iagaku@post.harvard.edu NR 21 TC 0 Z9 0 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 EI 1464-360X J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2015 VL 25 IS 2 BP 210 EP 215 DI 10.1093/eurpub/cku203 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CE9ZE UT WOS:000352201500009 PM 25488975 ER PT J AU Rastegar, N Matteoni-Athayde, LG Eng, J Takahashi, N Tamm, EP Mortele, KJ Syngal, S Margolis, D Lennon, AM Wolfgang, CL Fishman, EK Hruban, RH Goggins, M Canto, MI Kamel, IR AF Rastegar, Neda Matteoni-Athayde, Luciana G. Eng, John Takahashi, Naoki Tamm, Eric P. Mortele, Koenraad J. Syngal, Sapna Margolis, Daniel Lennon, Anne Marie Wolfgang, Christopher L. Fishman, Elliot K. Hruban, Ralph H. Goggins, Michael Canto, Marcia I. Kamel, Ihab R. TI Incremental value of secretin-enhanced magnetic resonance cholangiopancreatography in detecting ductal communication in a population with high prevalence of small pancreatic cysts SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Cyst; Magnetic resonance imaging; Neoplasm; Pancreas; Screening; Secretin ID HIGH-RISK INDIVIDUALS; PAPILLARY-MUCINOUS NEOPLASMS; MR CHOLANGIOPANCREATOGRAPHY; FAMILY-HISTORY; CANCER; LESIONS; YIELD; EUS AB Purpose: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. Methods: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses. Result: Of 202 individuals enrolled (mean age 56 years, 46% males), 93(46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128 =4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p = 0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p <0.0005). Conclusion: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Rastegar, Neda; Matteoni-Athayde, Luciana G.; Eng, John; Lennon, Anne Marie; Wolfgang, Christopher L.; Fishman, Elliot K.; Hruban, Ralph H.; Goggins, Michael; Canto, Marcia I.; Kamel, Ihab R.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Med Gastroenterol, Baltimore, MD USA. [Rastegar, Neda; Matteoni-Athayde, Luciana G.; Eng, John; Lennon, Anne Marie; Wolfgang, Christopher L.; Fishman, Elliot K.; Hruban, Ralph H.; Goggins, Michael; Canto, Marcia I.; Kamel, Ihab R.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Radiol, Baltimore, MD USA. [Takahashi, Naoki] Mayo Clin, Rochester, MN USA. [Tamm, Eric P.] MD Anderson Canc Ctr, Houston, TX USA. [Mortele, Koenraad J.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA USA. [Margolis, Daniel] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Kamel, IR (reprint author), Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, 1800 Orleans St,MRI 143, Baltimore, MD 21287 USA. EM ikamel@jhmi.edu FU National Cancer Institute (NCI) SPORE [CA62924] FX National Cancer Institute (NCI) SPORE (CA62924). Provided funds to recruit, image, and follow up high risk subjects. NR 28 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD APR PY 2015 VL 84 IS 4 BP 575 EP 580 DI 10.1016/j.ejrad.2014.12.028 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF6YZ UT WOS:000352704200005 PM 25619503 ER PT J AU Wu, H de Boer, JF Chen, L Chen, TC AF Wu, H. de Boer, J. F. Chen, L. Chen, T. C. TI Correlation of localized glaucomatous visual field defects and spectral domain optical coherence tomography retinal nerve fiber layer thinning using a modified structure-function map for OCT SO EYE LA English DT Article ID SCANNING LASER POLARIMETRY; OCULAR HYPERTENSION TREATMENT; STANDARD AUTOMATED PERIMETRY; GDX-VCC; THICKNESS; SENSITIVITY; EYES; ASSOCIATION; PARTICIPANTS; DISC AB Purpose To study the correlation between glaucomatous visual field (VF) defects assessed by standard automated perimetry (SAP) and peripapillary retinal nerve fiber layer (RNFL) thinning measured by spectral domain optical coherence tomography (OCT) using a modified OCT-based peripapillary RNFL structure-function map. Patients and methods Perimetric glaucoma patients and age-matched normal control subjects were recruited from a university hospital clinic. All eyes underwent testing with the Spectralis spectral domain OCT and SAP on the same day. An OCT-based correspondence map, which correlated VF areas with peripapillary RNFL sectors was created to evaluate the relationship between glaucomatous RNFL thinning and VF loss in six nerve fiber layer bundle areas. Correlations of RNFL thinning with corresponding VF defects were examined using Spearman rank-order correlations. To demonstrate the association between localized VF defects and RNFL thickness, the theoretical curves were made according to an established log-linear model. The measured RNFL thickness values and VF defects were presented in the same scatterplot for each sector. Results Fifty-six glaucoma patients and 85 normal subjects were included in the study. Significant association between localized VF loss and RNFL thinning was found in corresponding areas. Data from the current study fit well with established log-linear models, which compare RNFL thickness values with VF defects. Conclusion Analysis of RNFL thinning in eyes with localized glaucomatous VF defects showed good structure-function correlation in a new OCT-based structure-function correspondence map. C1 [Wu, H.; Chen, T. C.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Glaucoma Serv, Boston, MA 02114 USA. [Wu, H.] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China. [Wu, H.] Minist Educ, Key Lab Vis Loss & Restorat, Beijing, Peoples R China. [de Boer, J. F.] Vrije Univ Amsterdam, Dept Phys & Astron, Amsterdam, Netherlands. [Chen, L.] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol & Vis Sci, Shanghai Med Sch, Shanghai 200433, Peoples R China. [Chen, L.] Univ Hong Kong, Dept Ophthalmol, Hong Kong, Hong Kong, Peoples R China. RP Chen, TC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU National Institutes of Health [R01 EY14975-01] FX Gratitude is extended to Baojian Fan, PhD of the department of ophthalmology at the Harvard Medical School for statistical consultation. This study was supported in part by the National Institutes of Health (R01 EY14975-01). NR 29 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD APR PY 2015 VL 29 IS 4 BP 525 EP 533 DI 10.1038/eye.2014.317 PG 9 WC Ophthalmology SC Ophthalmology GA CF5WG UT WOS:000352627400013 PM 25633881 ER PT J AU Ashcroft, P Michor, F Galla, T AF Ashcroft, Peter Michor, Franziska Galla, Tobias TI Stochastic Tunneling and Metastable States During the Somatic Evolution of Cancer SO GENETICS LA English DT Article DE stochastic modeling; population genetics; cancer; Moran process; WKB method ID TUMOR-SUPPRESSOR GENES; MULTISTAGE CARCINOGENESIS; CHROMOSOMAL INSTABILITY; POPULATIONS; PROGRESSION; DYNAMICS; MUTATION; MODEL; SELECTION; TIME AB Tumors initiate when a population of proliferating cells accumulates a certain number and type of genetic and/or epigenetic alterations. The population dynamics of such sequential acquisition of (epi) genetic alterations has been the topic of much investigation. The phenomenon of stochastic tunneling, where an intermediate mutant in a sequence does not reach fixation in a population before generating a double mutant, has been studied using a variety of computational and mathematical methods. However, the field still lacks a comprehensive analytical description since theoretical predictions of fixation times are available only for cases in which the second mutant is advantageous. Here, we study stochastic tunneling in a Moran model. Analyzing the deterministic dynamics of large populations we systematically identify the parameter regimes captured by existing approaches. Our analysis also reveals fitness landscapes and mutation rates for which finite populations are found in long-lived metastable states. These are landscapes in which the final mutant is not the most advantageous in the sequence, and resulting metastable states are a consequence of a mutation-selection balance. The escape from these states is driven by intrinsic noise, and their location affects the probability of tunneling. Existing methods no longer apply. In these regimes it is the escape from the metastable states that is the key bottleneck; fixation is no longer limited by the emergence of a successful mutant lineage. We used the so-called Wentzel-Kramers-Brillouin method to compute fixation times in these parameter regimes, successfully validated by stochastic simulations. Our work fills a gap left by previous approaches and provides a more comprehensive description of the acquisition of multiple mutations in populations of somatic cells. C1 [Ashcroft, Peter; Galla, Tobias] Univ Manchester, Sch Phys & Astron, Theoret Phys, Manchester M13 9PL, Lancs, England. [Michor, Franziska] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Galla, T (reprint author), Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England. EM tobias.galla@manchester.ac.uk OI Ashcroft, Peter/0000-0003-4067-7692; Galla, Tobias/0000-0003-3402-2163 FU Engineering and Physical Sciences Council (United Kingdom), EPSRC; Dana-Farber Cancer Institute Physical Sciences-Oncology Center (National Institutes of Health) [U54CA143798]; EPSRC [EP/K037145/1] FX P.A. acknowledges support from the Engineering and Physical Sciences Council (United Kingdom), EPSRC. F.M. acknowledges support from the Dana-Farber Cancer Institute Physical Sciences-Oncology Center (National Institutes of Health U54CA143798). T.G. acknowledges support from the EPSRC, grant reference EP/K037145/1. NR 49 TC 0 Z9 0 U1 3 U2 16 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD APR PY 2015 VL 199 IS 4 BP 1213 EP 1228 DI 10.1534/genetics.114.171553 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA CF7KF UT WOS:000352734400024 PM 25624316 ER PT J AU Ramos, AH Lichtenstein, L Gupta, M Lawrence, MS Pugh, TJ Saksena, G Meyerson, M Getz, G AF Ramos, Alex H. Lichtenstein, Lee Gupta, Manaswi Lawrence, Michael S. Pugh, Trevor J. Saksena, Gordon Meyerson, Matthew Getz, Gad TI Oncotator: Cancer Variant Annotation Tool SO HUMAN MUTATION LA English DT Article DE oncotator; annotation; cancer; database; TCGA ID LUNG ADENOCARCINOMA; SOMATIC MUTATIONS; POINT MUTATIONS; PROSTATE-CANCER; SEQUENCING DATA; GENOME; LANDSCAPE; GENES; CONSEQUENCES; SIGNATURES AB Oncotator is a tool for annotating genomic point mutations and short nucleotide insertions/deletions (indels) with variant- and gene-centric information relevant to cancer researchers. This information is drawn from 14 different publicly available resources that have been pooled and indexed, and we provide an extensible framework to add additional data sources. Annotations linked to variants range from basic information, such as gene names and functional classification (e.g. missense), to cancer-specific data from resources such as the Catalogue of Somatic Mutations in Cancer (COSMIC), the Cancer Gene Census, and The Cancer Genome Atlas (TCGA). For local use, Oncotator is freely available as a python module hosted on Github (). Furthermore, Oncotator is also available as a web service and web application at . C1 [Ramos, Alex H.; Lichtenstein, Lee; Gupta, Manaswi; Lawrence, Michael S.; Pugh, Trevor J.; Saksena, Gordon; Meyerson, Matthew; Getz, Gad] Broad Inst, Canc Program, Cambridge, MA 02142 USA. [Ramos, Alex H.; Pugh, Trevor J.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ramos, Alex H.; Pugh, Trevor J.; Meyerson, Matthew; Getz, Gad] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Ramos, Alex H.; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ramos, Alex H.; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Getz, G (reprint author), Broad Inst, Canc Program, 415 Main St, Cambridge, MA 02142 USA. EM gadgetz@broadinstitute.org NR 57 TC 34 Z9 34 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2015 VL 36 IS 4 BP E2423 EP E2429 DI 10.1002/humu.22771 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CF1KO UT WOS:000352304200001 PM 25703262 ER PT J AU Blanch, L Villagra, A Sales, B Montanya, J Lucangelo, U Lujan, M Garcia-Esquirol, O Chacon, E Estruga, A Oliva, JC Hernandez-Abadia, A Albaiceta, GM Fernandez-Mondejar, E Fernandez, R Lopez-Aguilar, J Villar, J Murias, G Kacmarek, RM AF Blanch, Lluis Villagra, Ana Sales, Bernat Montanya, Jaume Lucangelo, Umberto Lujan, Manel Garcia-Esquirol, Oscar Chacon, Encarna Estruga, Anna Oliva, Joan C. Hernandez-Abadia, Alberto Albaiceta, Guillermo M. Fernandez-Mondejar, Enrique Fernandez, Rafael Lopez-Aguilar, Josefina Villar, Jesus Murias, Gaston Kacmarek, Robert M. TI Asynchronies during mechanical ventilation are associated with mortality SO INTENSIVE CARE MEDICINE LA English DT Article DE Patient-ventilator asynchrony; Mechanical ventilation; Mortality; Respiratory monitoring ID PRESSURE-SUPPORT VENTILATION; ACUTE RESPIRATORY-FAILURE; NEUROMUSCULAR BLOCKING-AGENTS; NONINVASIVE VENTILATION; DISTRESS-SYNDROME; SLEEP; MULTICENTER; ASSIST AB This study aimed to assess the prevalence and time course of asynchronies during mechanical ventilation (MV). Prospective, noninterventional observational study of 50 patients admitted to intensive care unit (ICU) beds equipped with Better Care (TM) software throughout MV. The software distinguished ventilatory modes and detected ineffective inspiratory efforts during expiration (IEE), double-triggering, aborted inspirations, and short and prolonged cycling to compute the asynchrony index (AI) for each hour. We analyzed 7,027 h of MV comprising 8,731,981 breaths. Asynchronies were detected in all patients and in all ventilator modes. The median AI was 3.41 % [IQR 1.95-5.77]; the most common asynchrony overall and in each mode was IEE [2.38 % (IQR 1.36-3.61)]. Asynchronies were less frequent from 12 pm to 6 am [1.69 % (IQR 0.47-4.78)]. In the hours where more than 90 % of breaths were machine-triggered, the median AI decreased, but asynchronies were still present. When we compared patients with AI > 10 vs AI a parts per thousand currency sign 10 %, we found similar reintubation and tracheostomy rates but higher ICU and hospital mortality and a trend toward longer duration of MV in patients with an AI above the cutoff. Asynchronies are common throughout MV, occurring in all MV modes, and more frequently during the daytime. Further studies should determine whether asynchronies are a marker for or a cause of mortality. C1 [Blanch, Lluis; Villagra, Ana; Garcia-Esquirol, Oscar; Chacon, Encarna; Estruga, Anna; Lopez-Aguilar, Josefina] Univ Autonoma Barcelona, Corp Sanitaria Univ Parc Tauli, Hosp Sabadell, Crit Care Ctr, Sabadell 08208, Spain. [Blanch, Lluis; Villagra, Ana; Sales, Bernat; Montanya, Jaume; Lujan, Manel; Albaiceta, Guillermo M.; Fernandez, Rafael; Lopez-Aguilar, Josefina; Villar, Jesus] ISCIII, CIBER Enfermedades Resp, Madrid, Spain. [Blanch, Lluis; Sales, Bernat; Montanya, Jaume; Garcia-Esquirol, Oscar; Oliva, Joan C.; Lopez-Aguilar, Josefina] Univ Autonoma Barcelona, Corp Sanitaria Univ Parc Tauli, Fundacio Parc Tauli, Sabadell 08208, Spain. [Lucangelo, Umberto] Univ Trieste, Cattinara Hosp, Dept Perioperat Med Intens Care & Emergency, Trieste, Italy. [Lujan, Manel] Univ Autonoma Barcelona, Corp Sanitaria Univ Parc Tauli, Dept Pneumol, Sabadell 08208, Spain. [Hernandez-Abadia, Alberto] Hosp Cent Defensa Gomez Ulla, Madrid, Spain. [Albaiceta, Guillermo M.] Univ Oviedo, Dept Funct Biol, Oviedo, Spain. [Albaiceta, Guillermo M.] Univ Oviedo, Hosp Cent Asturias, Dept Crit Care, E-33080 Oviedo, Spain. [Fernandez-Mondejar, Enrique] Univ Granada, Hosp Virgen Nieves, Dept Emergency & Crit Care Med, Granada, Spain. [Fernandez, Rafael] Univ Int Catalunya, Serv Med Intens, Fundacio Althaia, Manresa, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, MODERN, Las Palmas Gran Canaria, Spain. [Murias, Gaston] Clin Bazterr & Clin Santa Isabel, Buenos Aires, DF, Argentina. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. RP Blanch, L (reprint author), Univ Autonoma Barcelona, Corp Sanitaria Univ Parc Tauli, Hosp Sabadell, Crit Care Ctr, Parc Tauli 1, Sabadell 08208, Spain. EM LBlanch@tauli.cat RI Fernandez, Rafael/A-9586-2010; OI Fernandez, Rafael/0000-0001-5711-5317; Fernandez Mondejar, Enrique/0000-0003-1802-2016 FU ISCIII [PI09/91074, PI13/02204]; CIBER Enfermedades Respiratorias; Fundacion Mapfre; Fundacio Parc Tauli, Plan Avanza [TSI-020302-2008-38]; MCYIN; MITYC (Spain) FX The authors thank Merce Ruiz and Mr. John Giba for their invaluable support in editing the manuscript. This study was financially supported by ISCIII PI09/91074, PI13/02204, CIBER Enfermedades Respiratorias, Fundacion Mapfre, Fundacio Parc Tauli, Plan Avanza TSI-020302-2008-38, MCYIN and MITYC (Spain). No funding organization or sponsor was involved in the design or conduct of the study, in the collection, management, analysis, or interpretation of the data, or in the preparation, review, or approval of the manuscript.. NR 42 TC 40 Z9 41 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2015 VL 41 IS 4 BP 633 EP 641 DI 10.1007/s00134-015-3692-6 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA CF6FT UT WOS:000352653200007 PM 25693449 ER PT J AU Gans, JS AF Gans, Jerome S. TI The Insufficiency of Theory: Gaining One's Voice as a Group Therapist SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article C1 [Gans, Jerome S.] Harvard Univ, Sch Med, Psychiat, Cambridge, MA 02138 USA. [Gans, Jerome S.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02481 USA. EM jsgans@comcast.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0020-7284 EI 1943-2836 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 2015 VL 65 IS 2 BP 317 EP 325 PG 9 WC Psychology, Clinical SC Psychology GA CG1ZZ UT WOS:000353076000009 PM 25760791 ER PT J AU Beauchamp, B Ghosh, S Dysart, MW Kanaan, GN Chu, A Blais, A Rajamanickam, K Tsai, EC Patti, ME Harper, ME AF Beauchamp, B. Ghosh, S. Dysart, M. W. Kanaan, G. N. Chu, A. Blais, A. Rajamanickam, K. Tsai, E. C. Patti, M-E Harper, M-E TI Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID OXIDATIVE ENZYME-ACTIVITY; GENE-EXPRESSION; UNCOUPLING PROTEIN-3; CALORIC RESTRICTION; BODY-COMPOSITION; PROTON LEAK; FIBER TYPE; YOUNG MEN; GROWTH; OBESITY AB BACKGROUND: In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice. METHODS: We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level. RESULTS: U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction. CONCLUSIONS: Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood. C1 [Beauchamp, B.; Dysart, M. W.; Kanaan, G. N.; Chu, A.; Blais, A.; Harper, M-E] Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada. [Ghosh, S.] Duke NUS Grad Med Sch, Cardiovasc & Metab Disorders Program, Singapore, Singapore. [Chu, A.; Blais, A.; Harper, M-E] Univ Ottawa, Ottawa Inst Syst Biol, Ottawa, ON K1H 8M5, Canada. [Rajamanickam, K.; Tsai, E. C.] Univ Ottawa, Ottawa Hosp Res Inst, Fac Med, Div Neurosurg,Dept Surg, Ottawa, ON K1H 8M5, Canada. [Patti, M-E] Joslin Diabet Ctr, Div Integrat Physiol & Metab, Boston, MA 02215 USA. RP Harper, ME (reprint author), Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada. EM mharper@uottawa.ca RI Biguzzi, Felipe/E-4724-2015; OI Harper, Mary-Ellen/0000-0003-3864-5886; GHOSH, SUJOY/0000-0002-7601-165X FU Canadian Institutes of Health Research [MOP57810, MOP258677]; National Institutes of Health [P20MD000175, DK088319]; American Heart Association [AHA10SDG4230068]; Natural Sciences and Engineering Research Council of Canada FX We would like to thank Jian Xuan for technical assistance with animal work, Linda Jui for preparation and staining of histological slides, and Gabrielle Cote for assistance with counting muscle fibers. This research was supported through grants from Canadian Institutes of Health Research (MOP57810, M-EH; MOP258677, AB), National Institutes of Health (P20MD000175, DK088319; SG) and American Heart Association (AHA10SDG4230068; SG). Scholarships were also awarded from Natural Sciences and Engineering Research Council of Canada (Canada Graduate Scholarship -Doctoral, BB; -Master's, AC). NR 36 TC 7 Z9 7 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2015 VL 39 IS 4 BP 702 EP 711 DI 10.1038/ijo.2014.120 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CF4XO UT WOS:000352557500022 PM 25091727 ER PT J AU Williams, RF Smith, GP AF Williams, Ramone F. Smith, Gideon P. TI Using "Big Data" to Optimize Public Health Outreach Answering the Call to Action SO JAMA DERMATOLOGY LA English DT Editorial Material ID GOOGLE-TRENDS C1 [Williams, Ramone F.] Harvard Univ, Sch Med, Boston, MA USA. [Williams, Ramone F.; Smith, Gideon P.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Williams, RF (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Ste 200, Boston, MA 02114 USA. EM ramone.f.williams@gmail.com NR 7 TC 1 Z9 1 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2015 VL 151 IS 4 BP 367 EP 368 DI 10.1001/jamadermatol.2014.3176 PG 2 WC Dermatology SC Dermatology GA CF6FI UT WOS:000352652000001 PM 25390275 ER PT J AU Pascoe, VL Enamandram, M Corey, KC Cheng, CE Javorsky, EJ Sung, SM Donahue, KR Kimball, AB AF Pascoe, Vanessa L. Enamandram, Monica Corey, Kristen C. Cheng, Carol E. Javorsky, Emilia J. Sung, Sarah M. Donahue, Kevin R. Kimball, Alexandra B. TI Using the Physician Global Assessment in a Clinical Setting to Measure and Track Patient Outcomes SO JAMA DERMATOLOGY LA English DT Article ID SEVERITY-INDEX; ACNE-VULGARIS; PSORIASIS-AREA; MODERATE; DISEASE; DERMATOLOGISTS; PREVALENCE; EFFICACY; GEL AB IMPORTANCE In dermatology, the development of objective, standardized quality measures that can be used in a clinical setting is important to be able to respond to the needs of payers and credentialing and licensure bodies and to demonstrate dermatologic value. OBJECTIVE To examine the feasibility of using Physician Global Assessment (PGA) scores to collect and track patient acne and psoriasis outcomes over time. DESIGN, SETTING, AND PARTICIPANTS The PGA severity scoreswere included on physicians' billing sheets for patients with acne and psoriasis seen at a tertiary care center outpatient dermatology clinic from June 2011 through October 2012. A subset of patients from 5 clinics completed Patient Global Assessments (PtGAs) between November 2011 and May 2012. Thirty dermatology clinicians saw a total of 2770 patients with acne and 1516 patients with psoriasis in clinic, recording PGA scores for each patient. The PtGA scores were collected from 52 and 103 patients with acne and psoriasis, respectively, within the larger sample. MAIN OUTCOMES AND MEASURES Longitudinal PGA severity scoreswere collected for acne and psoriasis. The PGA severity scores were analyzed over time, with the hypothesis that patient scores for both acne and psoriasis would improve between the initial and follow-up visits. The PtGA scores from a subset of clinics and dates were compared with PGA scores to assess within-clinic reliability, with the hypothesis that there would be good agreement between clinician and patient assessments. RESULTS New patient PGA outcomes showed considerable improvement over time. At 3-month follow-up, 14.6% of the acne cohort was graded as effectively clear, compared with 2.1% at baseline (P < .001). Similarly, at 3-month follow-up, 22.3% of the psoriasis cohort was graded as effectively clear, compared with 3.1% at baseline (P < .001). Additionally, interobserver agreement between PGA and PtGA scores was good (acne, k = 0.68; psoriasis, k = 0.70). CONCLUSIONS AND RELEVANCE The PGA can be readily incorporated into practice to track patient acne and psoriasis outcomes over time, representing an opportunity for dermatologists to evaluate performance and validate practice guidelines. C1 [Pascoe, Vanessa L.; Cheng, Carol E.; Donahue, Kevin R.; Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Pascoe, Vanessa L.; Sung, Sarah M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Enamandram, Monica] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Corey, Kristen C.] Univ Massachusetts, Sch Med, Dept Dermatol, Worcester, MA USA. [Cheng, Carol E.; Kimball, Alexandra B.] Harvard Univ, Sch Med, Boston, MA USA. [Javorsky, Emilia J.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Ste 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU National Psoriasis Foundation fellowship; Department of Dermatology, Massachusetts General Hospital, Harvard Medical School FX Funding/Support: This study was supported in part by funds from a National Psoriasis Foundation fellowship (Dr Sung) and from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School. NR 21 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2015 VL 151 IS 4 BP 375 EP 381 PG 7 WC Dermatology SC Dermatology GA CF6FI UT WOS:000352652000004 PM 25549367 ER PT J AU Wehner, MR Linos, E Parvataneni, R Stuart, SE Boscardin, WJ Chren, MM AF Wehner, Mackenzie R. Linos, Eleni Parvataneni, Rupa Stuart, Sarah E. Boscardin, W. John Chren, Mary-Margaret TI Timing of Subsequent NewTumors in Patients Who Present With Basal Cell Carcinoma or Cutaneous Squamous Cell Carcinoma SO JAMA DERMATOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; RISK-FACTORS; SUNLIGHT EXPOSURE; METAANALYSIS; POPULATION; RECURRENCE AB IMPORTANCE Patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) (often termed nonmelanoma skin cancer or keratinocyte carcinoma [ KC]) often develop new KCs, but information is limited on the frequency and timing of these subsequent tumors. This information is crucial to guide follow-up care. OBJECTIVE To determine the timing of subsequent new KCs in patients who present with KC. DESIGN, SETTING, AND PARTICIPANTS We enrolled a consecutive cohort of 1426 patients diagnosed as having biopsy-proven KC from January 1, 1999, through December 31, 2000, in a university dermatology practice and its affiliated Department of Veterans Affairs dermatology service. After exclusion of patients with basal cell nevus syndrome and immunocompromise, 1284 patients (90.0%) were followed up prospectively for a mean of 5.7 (range, 0-12.3) years. MAIN OUTCOMES AND MEASURES We assessed the risks for subsequent KCs over time using single-failure and multiple-failure models. We separately assessed outcomes after first lifetime KCs and after nonfirst lifetime KCs. We also performed secondary analyses of the risk for a subsequent BCC after a prior BCC diagnosis and the risk for a subsequent SCC after a prior SCC diagnosis. RESULTS The risk for a subsequent KC was substantially lower after the first lifetime KC diagnosis: 14.5%(95% CI, 11.9%-17.7%) at 1 year, 31.1% (95% CI, 27.3%-35.3%) at 3 years, and 40.7%(95% CI, 36.5%-45.2%) at 5 years, than after a nonfirst KC: 43.9%(95% CI, 42.0%-45.9%) at 1 year, 71.1% (95% CI, 69.1%-73.0%) at 3 years, and 82.0%(95% CI, 80.2%-83.7%) at 5 years. Secondary analyses of the risks for a subsequent BCC after a prior BCC diagnosis and of a subsequent SCC after a prior SCC diagnosis yielded results consistent with the analyses for the pooled KC sample. CONCLUSIONS AND RELEVANCE Although all patients with KC are assumed to be at high risk for subsequent tumors, a subsetmay not develop another KC after their first tumor. Whether these findings are related to biological or behavioral differences or to differences in health care services should be investigated further to inform and improve care. Ongoing routine screening for subsequent KC may not be indicated for all patients with KC. Skin cancer screening can be improved with a better understanding of the course and frequency of subsequent KC diagnoses. C1 [Wehner, Mackenzie R.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA. RP Chren, MM (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Room N412,Box 0808, San Francisco, CA 94143 USA. EM chrenm@derm.ucsf.edu OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU Doris Duke Charitable Foundation; Dermatology Foundation; National Center for Research Resources of the National Institutes of Health (NIH) [KL2RR024130]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [R01 AR 054983, K24 AR052667] FX Funding/Support: This study was supported in part by grants from the Doris Duke Charitable Foundation (Dr Wehner), by the Dermatology Foundation (Dr Linos), by award KL2RR024130 from the National Center for Research Resources of the National Institutes of Health (NIH) (Dr Linos), and by grants R01 AR 054983 and K24 AR052667 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (Dr Chren). NR 24 TC 7 Z9 7 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD APR PY 2015 VL 151 IS 4 BP 382 EP 388 DI 10.1001/jamadermatol.2014.3307 PG 7 WC Dermatology SC Dermatology GA CF6FI UT WOS:000352652000005 PM 25588079 ER PT J AU Goodkind, M Eickhoff, SB Oathes, DJ Jiang, Y Chang, A Jones-Hagata, LB Ortega, BN Zaiko, YV Roach, EL Korgaonkar, MS Grieve, SM Galatzer-Levy, I Fox, PT Etkin, A AF Goodkind, Madeleine Eickhoff, Simon B. Oathes, Desmond J. Jiang, Ying Chang, Andrew Jones-Hagata, Laura B. Ortega, Brissa N. Zaiko, Yevgeniya V. Roach, Erika L. Korgaonkar, Mayuresh S. Grieve, Stuart M. Galatzer-Levy, Isaac Fox, Peter T. Etkin, Amit TI Identification of a Common Neurobiological Substrate for Mental Illness SO JAMA PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; VOXEL-BASED MORPHOMETRY; POSTTRAUMATIC-STRESS-DISORDER; LIKELIHOOD ESTIMATION METAANALYSIS; OBSESSIVE-COMPULSIVE DISORDER; AUTISM SPECTRUM DISORDER; GRAY-MATTER VOLUME; BIPOLAR-DISORDER; FUNCTIONAL CONNECTIVITY; ANTIPSYCHOTIC TREATMENT AB IMPORTANCE Psychiatric diagnoses are currently distinguished based on sets of specific symptoms. However, genetic and clinical analyses find similarities across a wide variety of diagnoses, suggesting that a common neurobiological substrate may exist across mental illness. OBJECTIVE To conduct a meta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses, followed by parallel analyses of 3 large-scale healthy participant data sets to help interpret structural findings in the meta-analysis. DATA SOURCES PubMed was searched to identify voxel-based morphometry studies through July 2012 comparing psychiatric patients to healthy control individuals for the meta-analysis. The 3 parallel healthy participant data sets included resting-state functional magnetic resonance imaging, a database of activation foci across thousands of neuroimaging experiments, and a data set with structural imaging and cognitive task performance data. DATA EXTRACTION AND SYNTHESIS Studies were included in the meta-analysis if they reported voxel-based morphometry differences between patients with an Axis I diagnosis and control individuals in stereotactic coordinates across the whole brain, did not present predominantly in childhood, and had at least 10 studies contributing to that diagnosis (or across closely related diagnoses). The meta-analysis was conducted on peak voxel coordinates using an activation likelihood estimation approach. MAIN OUTCOMES AND MEASURES We tested for areas of common gray matter volume increase or decrease across Axis I diagnoses, as well as areas differing between diagnoses. Follow-up analyses on other healthy participant data sets tested connectivity related to regions arising from the meta-analysis and the relationship of gray matter volume to cognition. RESULTS Based on the voxel-based morphometry meta-analysis of 193 studies comprising 15 892 individuals across 6 diverse diagnostic groups (schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety), we found that gray matter loss converged across diagnoses in 3 regions: the dorsal anterior cingulate, right insula, and left insula. By contrast, there were few diagnosis-specific effects, distinguishing only schizophrenia and depression from other diagnoses. In the parallel follow-up analyses of the 3 independent healthy participant data sets, we found that the common gray matter loss regions formed a tightly interconnected network during tasks and at resting and that lower gray matter in this network was associated with poor executive functioning. CONCLUSIONS AND REVELANCE We identified a concordance across psychiatric diagnoses in terms of integrity of an anterior insula/dorsal anterior cingulate-based network, which may relate to executive function deficits observed across diagnoses. This concordance provides an organizing model that emphasizes the importance of shared neural substrates across psychopathology, despite likely diverse etiologies, which is currently not an explicit component of psychiatric nosology. C1 [Goodkind, Madeleine; Oathes, Desmond J.; Jiang, Ying; Chang, Andrew; Jones-Hagata, Laura B.; Ortega, Brissa N.; Zaiko, Yevgeniya V.; Roach, Erika L.; Etkin, Amit] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. [Goodkind, Madeleine; Oathes, Desmond J.; Jiang, Ying; Chang, Andrew; Jones-Hagata, Laura B.; Ortega, Brissa N.; Zaiko, Yevgeniya V.; Roach, Erika L.; Etkin, Amit] Sierra Pacif Mental Illness Res Educ & Clin Ctr M, Palo Alto, CA USA. [Goodkind, Madeleine; Oathes, Desmond J.; Jiang, Ying; Chang, Andrew; Jones-Hagata, Laura B.; Ortega, Brissa N.; Zaiko, Yevgeniya V.; Roach, Erika L.; Etkin, Amit] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Eickhoff, Simon B.] Res Ctr Julich, INM 1, Julich, Germany. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Korgaonkar, Mayuresh S.; Grieve, Stuart M.] Westmead Millennium Inst, Brain Dynam Ctr, Sydney, NSW, Australia. [Korgaonkar, Mayuresh S.; Grieve, Stuart M.] Sydney Med Sc Westmead, Sydney, NSW, Australia. [Korgaonkar, Mayuresh S.; Grieve, Stuart M.] Univ Sydney, Sydney Med Sch, Sydney Translat Imaging Lab, Sydney, NSW 2006, Australia. [Galatzer-Levy, Isaac] NYU, Dept Psychiat, New York, NY 10016 USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, Sch Humanities, Hong Kong, Hong Kong, Peoples R China. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. RP Etkin, A (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, 401 Quarry Rd,MC 5797, Stanford, CA 94305 USA. EM amitetkin@stanford.edu RI Eickhoff, Simon/K-2061-2013; OI Eickhoff, Simon/0000-0001-6363-2759; Oathes, Desmond/0000-0001-7346-2669; Galatzer-Levy, Isaac/0000-0003-1864-064X FU Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) at the Palo Alto Veterans Affairs; Deutsche Forschungsgemeinschaft [EI 816/4-1, LA 3071/3-1]; National Institute of Mental Health [R01-MH074457]; European Commission (Human Brain Project); National Health and Medical Research Council of Australia project grants scheme [1008080]; Sydney University Medical Foundation; National Institutes of Health/National Institute of Mental Health Award [RO1 MH074457] FX Drs Goodkind and Etkin were funded by the Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) at the Palo Alto Veterans Affairs. Dr Eickhoff was supported by the Deutsche Forschungsgemeinschaft (EI 816/4-1; SBE and LA 3071/3-1), the National Institute of Mental Health (R01-MH074457), and the European Commission (Human Brain Project). Drs Korgaonkar and Grieve were funded by the National Health and Medical Research Council of Australia project grants scheme (project grant 1008080) and the Sydney University Medical Foundation. Comprehensive access to the BrainMap database was authorized by a collaborative-use license agreement. BrainMap is supported by National Institutes of Health/National Institute of Mental Health Award RO1 MH074457. All VBM studies reported in this article are now coded and accessible through BrainMap. NR 86 TC 95 Z9 96 U1 15 U2 71 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD APR PY 2015 VL 72 IS 4 BP 305 EP 315 DI 10.1001/jamapsychiatry.2014.2206 PG 11 WC Psychiatry SC Psychiatry GA CF3ZF UT WOS:000352487000002 PM 25651064 ER PT J AU Hirschtritt, ME Lee, PC Pauls, DL Dion, Y Grados, MA Illmann, C King, RA Sandor, P McMahon, WM Lyon, GJ Cath, DC Kurlan, R Robertson, MM Osiecki, L Scharf, JM Mathews, CA AF Hirschtritt, Matthew E. Lee, Paul C. Pauls, David L. Dion, Yves Grados, Marco A. Illmann, Cornelia King, Robert A. Sandor, Paul McMahon, William M. Lyon, Gholson J. Cath, Danielle C. Kurlan, Roger Robertson, Mary M. Osiecki, Lisa Scharf, Jeremiah M. Mathews, Carol A. CA Tourette Syndrome Assoc Int Consor TI Lifetime Prevalence, Age of Risk, and Genetic Relationships of Comorbid Psychiatric Disorders in Tourette Syndrome SO JAMA PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; OF-ONSET DISTRIBUTIONS; TIC DISORDERS; CLINICAL-FEATURES; CHILDREN; PSYCHOPATHOLOGY; SEVERITY; ADOLESCENTS; DEPRESSION AB IMPORTANCE Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS. OBJECTIVE To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142). MAIN OUTCOMES AND MEASURES Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history. RESULTS The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95% CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9-4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32-2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD. CONCLUSIONS AND RELEVANCE This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS. C1 [Hirschtritt, Matthew E.; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, Program Genet & Epidemiol Neuropsychiat Symptoms, San Francisco, CA 94143 USA. [Lee, Paul C.; Pauls, David L.; Illmann, Cornelia; Osiecki, Lisa; Scharf, Jeremiah M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA USA. [Dion, Yves] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Grados, Marco A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [King, Robert A.] Yale Univ, Sch Med, Yale Child Study Ctr, Dept Genet, New Haven, CT USA. [Sandor, Paul] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Sandor, Paul] Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada. [Sandor, Paul] Youthdale Treatment Ctr, Toronto, ON, Canada. [McMahon, William M.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Lyon, Gholson J.] Stanley Inst Cognit Gen, Cold Spring Harbor Lab, Woodbury, NY USA. [Cath, Danielle C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [Cath, Danielle C.] Altrecht Acad Anxiety Disorders Ctr, Utrecht, Netherlands. [Kurlan, Roger] Overlook Hosp, Atlant Neurosci Inst, Summit, NJ USA. [Robertson, Mary M.] UCL, London, England. [Robertson, Mary M.] St George Hosp, London, England. [Robertson, Mary M.] Sch Med, London, England. [Robertson, Mary M.] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. [Scharf, Jeremiah M.] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Scharf, Jeremiah M.] MIT, Cambridge, MA 02139 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mathews, CA (reprint author), Univ Calif San Francisco, Dept Psychiat, Program Genet & Epidemiol Neuropsychiat Symptoms, 401 Parnassus Ave,POB 0984, San Francisco, CA 94143 USA. EM carolm@lppi.ucsf.edu OI Barr, Cathy/0000-0003-0361-0106 FU National Institutes of Health grant from the National Institute of Neurological Disorders and Stroke [U01 NS40024]; National Institute of Mental Health [K23 MH085057, R01 MH096767]; Doris Duke Clinical Research Fellowship FX This study was supported in part by National Institutes of Health grant U01 NS40024 (Dr Scharf) from the National Institute of Neurological Disorders and Stroke, grants K23 MH085057 (Dr Scharf) and R01 MH096767 (Dr Mathews) from the National Institute of Mental Health, and by a Doris Duke Clinical Research Fellowship (Dr Hirschtritt). NR 49 TC 43 Z9 44 U1 3 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD APR PY 2015 VL 72 IS 4 BP 325 EP 333 DI 10.1001/jamapsychiatry.2014.2650 PG 9 WC Psychiatry SC Psychiatry GA CF3ZF UT WOS:000352487000004 PM 25671412 ER PT J AU Pietrzak, RH Averill, LA Abdallah, CG Neumeister, A Krystal, JH Levy, I Harpaz-Rotem, I AF Pietrzak, Robert H. Averill, Lynnette A. Abdallah, Chadi G. Neumeister, Alexander Krystal, John H. Levy, Ifat Harpaz-Rotem, Ilan TI Amygdala-Hippocampal Volume and the Phenotypic Heterogeneity of Posttraumatic Stress Disorder: A Cross-Sectional Study SO JAMA PSYCHIATRY LA English DT Letter ID INDIVIDUAL-DIFFERENCES; METAANALYSIS C1 [Pietrzak, Robert H.; Averill, Lynnette A.; Abdallah, Chadi G.; Krystal, John H.; Levy, Ifat; Harpaz-Rotem, Ilan] Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, VA Connecticut Healthcare Syst, Clin Neurosci Div, West Haven, CT 06516 USA. [Pietrzak, Robert H.; Averill, Lynnette A.; Abdallah, Chadi G.; Krystal, John H.; Harpaz-Rotem, Ilan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Neumeister, Alexander] NYU, Sch Med, Dept Radiol, New York, NY USA. [Levy, Ifat] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06510 USA. RP Pietrzak, RH (reprint author), VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, 950 Campbell Ave,151E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu OI Abdallah, Chadi/0000-0001-5783-6181 FU Clinical Neurosciences Division of the US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, grant from the National Institutes of Health [K23 MH-101498] FX Preparation of this study was supported in part by the Clinical Neurosciences Division of the US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, grant K23 MH-101498 from the National Institutes of Health (Dr Abdallah), and a private donation. NR 6 TC 3 Z9 4 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD APR PY 2015 VL 72 IS 4 BP 396 EP 398 DI 10.1001/jamapsychiatry.2014.2470 PG 4 WC Psychiatry SC Psychiatry GA CF3ZF UT WOS:000352487000013 PM 25692480 ER PT J AU King, JT Perkal, MF Rosenthal, RA Gordon, AJ Crystal, S Rodriguez-Barradas, MC Butt, AA Gibert, CL Rimland, D Simberkoff, MS Justice, AC AF King, Joseph T., Jr. Perkal, Melissa F. Rosenthal, Ronnie A. Gordon, Adam J. Crystal, Stephen Rodriguez-Barradas, Maria C. Butt, Adeel A. Gibert, Cynthia L. Rimland, David Simberkoff, Michael S. Justice, Amy C. TI Thirty-Day Postoperative Mortality Among Individuals With HIV Infection Receiving Antiretroviral Therapy and Procedure-Matched, Uninfected Comparators SO JAMA SURGERY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSITIVE PATIENTS; CD4 COUNT; ABDOMINAL OPERATIONS; KIDNEY-TRANSPLANTATION; LIVER-TRANSPLANTATION; SURGICAL-TREATMENT; PROGNOSTIC-FACTOR; CESAREAN-SECTION; LIFE EXPECTANCY AB IMPORTANCE Antiretroviral therapy (ART) has converted human immunodeficiency virus (HIV) infection into a chronic condition, and patients now undergo a variety of surgical procedures, but current surgical outcomes are inadequately characterized. OBJECTIVE To compare 30-day postoperative mortality in patients with HIV infection receiving ART with the rates in uninfected individuals. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of nationwide electronic medical record data from the US Veterans Health Administration Healthcare System, October 1, 1996, to September 30, 2010. Common inpatient surgical procedures were grouped using the Healthcare Cost and Utilization Project Clinical Classification System to match HIV-infected and uninfected patients in a 1: 2 ratio. Data on 1641 patients with HIV infection receiving combination ART who were undergoing inpatient surgery were compared with data on 3282 procedure-matched, uninfected comparators. Poisson regression models of 30-day postoperative mortality were adjusted for procedure year, age, Charlson Comorbidity Index score, hemoglobin level, albumin level, HIV infection, CD4 cell count, and HIV-1 RNA level. MAIN OUTCOMES AND MEASURES All-cause 30-day postoperative mortality. RESULTS The most common procedures in both groups were cholecystectomy (10.5%), hip arthroplasty (10.5%), spine surgery (9.8%), herniorrhaphy (7.4%), and coronary artery bypass grafting (7.0%). In patients with HIV infection, CD4 cell distributions were 80.0% with 200/mu L or more, 16.3% with 50/mu L to 199/mu L, and 3.7% with less than 50/mu L; 74.1% of patients with HIV infection had undetectable HIV-1 RNA. Human immunodeficiency virus infection was associated with higher 30-day postoperative mortality compared with the mortality in uninfected patients (3.4%[56 patients]) vs 1.6%[53]); incidence rate ratio [IRR], 2.11; 95% CI, 1.41-3.17; P < .001). CD4 cell count was inversely associated with mortality, but HIV-1 RNA provided no additional information. After adjustment, patients with HIV infection had increased mortality compared with uninfected patients at all CD4 cell count strata (>= 500/mu L: IRR, 1.92; 95% CI, 1.02-3.60; P =.04; 200-499/mu L: IRR, 1.89; 95% CI, 1.20-2.98; P = .01; 50-199/mu L: IRR, 2.66; 95% CI, 1.29-5.47; P = .01; and < 50/mu L: IRR, 6.21; 95% CI, 3.55-10.85; P < .001). Hypoalbuminemia (IRR, 4.35; 95% CI, 2.78-6.81; P < .001) and age in decades (IRR, 1.47; 95% CI, 1.23-1.76; P < .001) were also strongly associated with mortality. CONCLUSIONS AND RELEVANCE Current postoperative mortality rates among individuals with HIV infection who are receiving ART are low and are influenced as much by hypoalbuminemia and age as by CD4 cell status. Human immunodeficiency virus infection and CD4 cell count are only 2 of many factors associated with surgical outcomes that should be incorporated into surgical decision making. C1 [King, Joseph T., Jr.] Vet Affairs VA Connecticut Healthcare Syst, Dept Surg, Sect Neurosurg, West Haven, CT USA. [King, Joseph T., Jr.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Perkal, Melissa F.; Rosenthal, Ronnie A.] VA Connecticut Healthcare Syst, Sect Gen Surg, Dept Surg, West Haven, CT USA. [Perkal, Melissa F.; Rosenthal, Ronnie A.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Gordon, Adam J.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Gordon, Adam J.; Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Gordon, Adam J.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA. [Crystal, Stephen] Rutgers State Univ, Ctr Hlth Serv Res Pharmacotherapy Chron Dis Manag, New Brunswick, NJ 08903 USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Dept Med, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Gibert, Cynthia L.] VA Med Ctr, Med Serv, Infect Dis Sect, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Sch Med & Hlth Sci, Dept Med, Washington, DC 20052 USA. [Rimland, David] Atlanta VA Med Ctr, Dept Med, Div Infect Dis, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. [Simberkoff, Michael S.] VA New York Harbor Healthcare Syst, Dept Med, Infect Dis Sect, New York, NY USA. [Simberkoff, Michael S.] NYU, Sch Med, Dept Med, Infect Dis Sect, New York, NY USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Med, Gen Internal Med Sect, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. RP King, JT (reprint author), Vet Affairs Connecticut Healthcare Syst, Dept Surg 113, Sect Neurosurg, 950 Campbell Ave, West Haven, CT 06516 USA. EM joseph.kingjr@va.gov OI Butt, Adeel/0000-0002-1118-1826; Justice, Amy/0000-0003-0139-5502 FU National Institutes of Health: National Institute on Alcohol Abuse and Alcoholism [U10-AA13566]; National Institutes of Health: National Institute on Aging [R01-AG029154]; National Institutes of Health: National Heart, Lung, and Blood Institute [R01-HL095136, R01-HL090342, RCI-HL100347]; National Institutes of Health: National Institute of Allergy and Infectious Disease [U01-A1069918]; National Institutes of Health: National Institute of Mental Health [P30-MH062294]; National Institutes of Health: Agency for Healthcare Research and Quality [U19-HS-021112]; Veterans Health Administration Office of Research and Development [VA REA 8-266]; Office of Academic Affiliations (Medical Informatics Fellowship) FX This work was supported by grants from the National Institutes of Health: National Institute on Alcohol Abuse and Alcoholism (U10-AA13566), National Institute on Aging (R01-AG029154), National Heart, Lung, and Blood Institute (R01-HL095136; R01-HL090342; RCI-HL100347), National Institute of Allergy and Infectious Disease (U01-A1069918), National Institute of Mental Health (P30-MH062294), Agency for Healthcare Research and Quality (U19-HS-021112), and the Veterans Health Administration Office of Research and Development (VA REA 8-266) and Office of Academic Affiliations (Medical Informatics Fellowship). NR 76 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2015 VL 150 IS 4 BP 343 EP 351 DI 10.1001/jamasurg.2014.2257 PG 9 WC Surgery SC Surgery GA CG0EB UT WOS:000352938300011 PM 25714794 ER PT J AU Parsons, JK Chang, D AF Parsons, J. Kellogg Chang, David TI Faulty Analysis in Study of Robotic-Assisted Minimally Invasive Radical Prostatectomy Reply SO JAMA SURGERY LA English DT Letter ID OUTCOMES C1 [Parsons, J. Kellogg] Univ Calif San Diego, Dept Urol, Heath Syst, La Jolla, CA 92093 USA. [Parsons, J. Kellogg] Univ Calif San Diego, Urol Canc Unit, Moores Canc Ctr, La Jolla, CA 92093 USA. [Parsons, J. Kellogg] VA San Diego Healthcare Syst, Sect Surg, La Jolla, CA USA. [Chang, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Parsons, JK (reprint author), Univ Calif San Diego, Urol Canc Unit, 3855 Hlth Sci Dr,Ste 0987, La Jolla, CA 92093 USA. EM jkparsons@ucsd.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD APR PY 2015 VL 150 IS 4 BP 372 EP 372 DI 10.1001/jamasurg.2015.45 PG 1 WC Surgery SC Surgery GA CG0EB UT WOS:000352938300021 PM 25714658 ER PT J AU Alosco, ML Spitznagel, MB Cohen, R Sweet, LH Hayes, SM Josephson, R Hughes, J Gunstad, J AF Alosco, Michael L. Spitznagel, Mary Beth Cohen, Ronald Sweet, Lawrence H. Hayes, Scott M. Josephson, Richard Hughes, Joel Gunstad, John TI Decreases in Daily Physical Activity Predict Acute Decline in Attention and Executive Function in Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Physical activity; heart failure; cognitive function; accelerometry ID CEREBRAL-BLOOD-FLOW; OLDER-ADULTS; COGNITIVE FUNCTION; CARDIAC REHABILITATION; ALZHEIMERS-DISEASE; AEROBIC FITNESS; ACCELEROMETER; RISK; PERFORMANCE; CALIBRATION AB Background: Reduced physical activity (PA) may be one factor that contributes to cognitive decline and dementia in heart failure (HF). Yet, the longitudinal relationship between PA and cognition in HF is poorly understood owing to limitations of past work, including single-time assessments of PA. This is the first study to examine changes in objectively measured PA and cognition over time in HF. Methods and Results: At baseline and 12 weeks, 57 HF patients completed psychosocial self-report measures and a neuropsychological battery and wore an accelerometer for 7 days. At baseline, HF patients spent an average of 597.83 (SD 75.91) minutes per day sedentary. Steps per day declined from baseline to the 12-week follow-up; there was also a trend for declines in moderate-vigorous PA. Regression analyses controlling for sex, HF severity, and depressive symptoms showed that decreases in light (P = .08) and moderate-vigorous (P = .04) daily PA emerged as strong predictors of declines in attention/executive function over the 12-week period, but not of memory or language. Conclusions: Reductions in daily PA predicted acute decline in attention/executive function in HF, but not of memory or language. Modifications to daily PA may attenuate cognitive decline, and prospective studies are needed to test this possibility. C1 [Alosco, Michael L.; Spitznagel, Mary Beth; Hughes, Joel; Gunstad, John] Kent State Univ, Dept Psychol Sci, Kent, OH 44242 USA. [Cohen, Ronald] Univ Florida, Dept Neurol Psychiat, Gainesville, FL USA. [Cohen, Ronald] Univ Florida, Inst Aging, Ctr Cognit Aging & Memory, Gainesville, FL USA. [Sweet, Lawrence H.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Hayes, Scott M.] Vet Affairs Boston Healthcare Syst, Mem Disorders Res Ctr, Boston, MA USA. [Hayes, Scott M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hayes, Scott M.] Vet Affairs Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Josephson, Richard] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [Josephson, Richard] Harrington Heart & Vasc Inst, Cleveland, OH USA. [Josephson, Richard; Hughes, Joel] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. RP Gunstad, J (reprint author), Kent State Univ, Dept Psychol, Kent, OH 44242 USA. EM jgunstad@kent.edu FU National Institutes of Health [DK075119, HL089311] FX National Institutes of Health grants DK075119 and HL089311. NR 46 TC 6 Z9 6 U1 2 U2 18 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD APR PY 2015 VL 21 IS 4 BP 339 EP 346 DI 10.1016/j.cardfail.2014.12.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF3RU UT WOS:000352467000008 PM 25573830 ER PT J AU Bayes-Genis, A Januzzi, JL Gaggin, HK de Antonio, M Motiwala, SR Zamora, E Galan, A Domingo, M Urrutia, A Lupon, J AF Bayes-Genis, Antoni Januzzi, James L. Gaggin, Hanna K. de Antonio, Marta Motiwala, Shweta R. Zamora, Elisabet Galan, Amparo Domingo, Mar Urrutia, Agustin Lupon, Josep TI ST2 Pathogenetic Profile in Ambulatory Heart Failure Patients SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; biomarkers; prognosis ID INTERLEUKIN-1 RECEPTOR FAMILY; VENTRICULAR SYSTOLIC DYSFUNCTION; HELPER T-CELLS; NATRIURETIC PEPTIDE; SOLUBLE ST2; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; TROPONIN-T; PROTEIN; EXPRESSION AB Background: Soluble ST2 is involved in multiple pathogenic pathways, including cardiac strain, inflammation, and myocardial necrosis with remodeling. The relative weight of ST2 and the point at which its prognostic value in heart failure (HF) is affected by different degrees of myocardial strain, inflammation, necrosis, and remodeling is unknown. Methods and Results: We examined whether soluble ST2 levels improves HF risk stratification relative to other biomarkers representative of multiple pathogenic pathways N-terminal pro B-type natriuretic peptide (NT-proBNP; strain), high-sensitivity C-reactive protein (hsCRP; inflammation), and galectin-3 and high-sensitivity troponin T (hsTnT; necrosis and remodeling) in 1,015 patients with mean left ventricular ejection fraction (LVEF) 33.5%. Mean follow-up was 4.2 +/- 2.1 years. The correlation with soluble ST2 was highest with NT-proBNP (r = 0.32; P < .001) and lowest with galectin-3 (r = 0.15; P < .001). ST2 levels increased with increasing concentrations of the other biomarkers (P < .001 in all cases). During follow-up, 467 patients died. Soluble ST2 remained an independent prognosticator of risk at every tertile of each biomarker. This was observed even after adjusting for clinical parameters. Conclusions: Soluble ST2 may be regarded as a 3-in-1 prognosis biomarker in HF. ST2 provides valuable long-term risk stratification information in HF beyond that reported by other biomarkers of stretch, inflammation, necrosis, and remodeling. C1 [Bayes-Genis, Antoni; de Antonio, Marta; Zamora, Elisabet; Domingo, Mar; Urrutia, Agustin; Lupon, Josep] Hosp Badalona Germans Trias & Pujol, Dept Cardiol, Heart Failure Unit, Badalona 08916, Spain. [Bayes-Genis, Antoni; de Antonio, Marta; Zamora, Elisabet; Urrutia, Agustin; Lupon, Josep] Autonomous Univ Barcelona, Dept Med, Barcelona, Spain. [Januzzi, James L.; Gaggin, Hanna K.; Motiwala, Shweta R.] Massachusetts Gen Hosp, Dept Med, Cardiol Div, Boston, MA 02114 USA. [Galan, Amparo] Hosp Badalona Germans Trias & Pujol, Dept Biochem, Badalona 08916, Spain. RP Bayes-Genis, A (reprint author), Hosp Badalona Germans Trias & Pujol, Dept Med, Carretera Canyet S-N, Badalona 08916, Spain. EM abayesgenis@gmail.com OI Lupon, Josep/0000-0002-5601-9611 FU Redes Tematicas de Investigacion Cooperativa en Salud (RETICS) Red Cardiovascular [RD12/0042/0047] FX Redes Tematicas de Investigacion Cooperativa en Salud (RETICS) Red Cardiovascular (RD12/0042/0047). NR 35 TC 3 Z9 3 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD APR PY 2015 VL 21 IS 4 BP 355 EP 361 DI 10.1016/j.cardfail.2014.10.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF3RU UT WOS:000352467000010 PM 25451702 ER PT J AU Kanmanthareddy, A Vallakati, A Yeruva, MR Dixit, S Di Biase, L Mansour, M Boolani, H Gunda, S Bunch, TJ Day, JD Ruskin, JN Buddam, A Koripalli, S Bommana, S Natale, A Lakkireddy, D AF Kanmanthareddy, Arun Vallakati, Ajay Yeruva, Madhu Reddy Dixit, Sanjay Di Biase, Luigi Mansour, Moussa Boolani, Hemant Gunda, Sampath Bunch, T. Jared Day, John D. Ruskin, Jeremy N. Buddam, Avanija Koripalli, Sandeep Bommana, Sudharani Natale, Andrea Lakkireddy, Dhanunjaya TI Pulmonary Vein Isolation for Atrial Fibrillation in the Postpneumonectomy Population: A Feasibility, Safety, and Outcomes Study SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation ablation; atrial fibrillation after pneumonectomy; catheter ablation of pulmonary vein stump; efficacy of isolation of pulmonary vein stump; pulmonary vein stump ID RADIOFREQUENCY ABLATION; LUNG-CANCER; PNEUMONECTOMY; INITIATION; RESECTION; TRIGGERS AB AF Ablation in Pulmonary Vein Stumps BackgroundPulmonary vein isolation (PVI) of the remnant pulmonary vein (PV) stumps in pneumonectomy patients has not been well characterized. MethodsThis is a multicenter observational study of patients with a remnant PV stump after pneumonectomy. Consecutive patients with a history of pneumonectomy and who had undergone RF ablation for drug refractory AF were identified from the AF database at the participating institutions. ResultsThere were 15 patients in whom pneumonectomy was performed, for resection of tumors in 10, infection in 4, and bullae in 1 patient and who underwent RF ablation for AF. The mean age was 63 7 years. The stumps were from the right lower PV in 5, left upper PV in 5, left lower PV in 3, and right upper PV in 2 patients. All the PV stumps were electrically active with PV potentials and 9 (60%) of them had triggered activity. PVI was performed in 14 and focal isolation in 1 patient. At 1-year follow-up, 80% were free of AF, off of antiarrhythmic medications. ConclusionPV stumps in AF patients with previous pneumonectomy are electrically active and are frequently the sites of active firing. Isolation of these PV stumps can be accomplished safely and effectively using catheter ablation with no practical concern for PV stenosis or compromising PV stump integrity. C1 [Kanmanthareddy, Arun] Creighton Univ, Div Cardiol, Omaha, NE 68178 USA. [Vallakati, Ajay] Case Western Reserve Univ, MetroHlth Med Ctr, Div Cardiol, Cleveland, OH 44106 USA. [Yeruva, Madhu Reddy; Gunda, Sampath; Bunch, T. Jared; Buddam, Avanija; Koripalli, Sandeep; Bommana, Sudharani; Lakkireddy, Dhanunjaya] Univ Kansas Hosp, KU Cardiovasc Res Inst, Kansas City, KS 66160 USA. [Yeruva, Madhu Reddy; Gunda, Sampath; Bunch, T. Jared; Buddam, Avanija; Koripalli, Sandeep; Bommana, Sudharani; Lakkireddy, Dhanunjaya] Med Ctr, Kansas City, KS 66160 USA. [Dixit, Sanjay] Hosp Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Di Biase, Luigi] Albert Einstein Montefiore Med Ctr, Div Cardiol, Bronx, NY USA. [Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Boolani, Hemant] Howard Univ Hosp, Div Cardiol, Washington, DC USA. [Day, John D.] Intermt Heart Inst, Div Cardiol, Salt Lake City, UT USA. [Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Div Elect, Austin, TX USA. RP Lakkireddy, D (reprint author), Univ Kansas Hosp, KU Cardiovasc Res Inst, Ctr Excellence Atrial Fibrillat & Electrophysiol, Bloch Heart Rhythm Ctr,Mid Amer Cardiol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM dlakkireddy@kumc.edu OI Di Biase, Luigi/0000-0001-6508-4047 FU Advanced Medical Information; CardioInsight; Cardiome; Gilead Sciences; Medtronic; Pfizer FX LDB reports serving as a consultant for Biosense Webster, St. Jude Medical, Medtronic, Biotronik, EpiEP. TJB reports serving as a consultant/advisory board member for Boston Scientific. JNR reports equity interest in InfoBionic and Portola; consulting fees from Advanced Medical Information, CardioInsight, Cardiome, Gilead Sciences, Medtronic, and Pfizer; and honorarium from Sanofi Aventis. Other authors: No disclosures. NR 17 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2015 VL 26 IS 4 BP 385 EP 389 DI 10.1111/jce.12619 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF8MH UT WOS:000352814300008 PM 25588757 ER PT J AU Voscopoulos, CJ MacNabb, CM Brayanov, J Qin, LZ Freeman, J Mullen, GJ Ladd, D George, E AF Voscopoulos, Christopher J. MacNabb, C. Marshall Brayanov, Jordan Qin, Lizeng Freeman, Jenny Mullen, Gary John Ladd, Diane George, Edward TI The evaluation of a non-invasive respiratory volume monitor in surgical patients undergoing elective surgery with general anesthesia SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE Non-invasive respiratory volume monitoring; Thoracic bio-impedance; General anesthesia; Ventilation monitoring in non-intubated patients ID PULSE OXIMETRY; VENTILATION; ACCURACY AB Continuous respiratory assessment is especially important during post-operative care following extubation. Respiratory depression and subsequent adverse outcomes can arise due to opioid administration and/or residual anesthetics. A non-invasive respiratory volume monitor (RVM) has been developed that provides continuous, real-time, measurements of minute ventilation (MV), tidal volume (TV), and respiratory rate (RR) via a standardized set of thoracic electrodes. Previous work demonstrated accuracy of the RVM versus standard spirometry and its utility in demonstrating response to opioids in postoperative patients. This study evaluated the correlation between RVM measurements of MV, TV and RR to ventilator measurements during general anesthesia (GA). Continuous digital RVM and ventilator traces, as well as RVM measurements of MV, TV and RR, were analyzed from ten patients (mean 62.6 +/- A 7.4 years; body mass index 28.6 +/- A 5.2 kg/m(2)) undergoing surgery with GA. RVM data were compared to ventilator data and bias, precision and accuracy were calculated. The average MV difference between the RVM and ventilator was -0.10 L/min (bias: -1.3 %, precision: 6.6 %, accuracy: 9.0 %. The average TV difference was 40 mL (bias: 0.4 %, precision: 7.3 %, accuracy: 9.1 %). The average RR difference was -0.22 breaths/minute (bias: -1.8 %, precision: 3.7 % accuracy: 4.1 %). Correlations between the RVM traces and the ventilator were compared at various points with correlations > 0.90 throughout. Pairing the close correlation to ventilator measurements in intubated patients demonstrated by this study with previously described accuracy compared to spirometry in non-intubated patients, the RVM can be considered to have the capability to provide continuity of ventilation monitoring post-extubation This supports the use of real-time continuous RVM measurements to drive post-operative and post-extubation protocols, initiate therapeutic interventions and improve patient safety. C1 [Voscopoulos, Christopher J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Pain & Perioperat Med, Boston, MA 02115 USA. [MacNabb, C. Marshall; Brayanov, Jordan; Freeman, Jenny; Ladd, Diane] Resp Mot Inc, Waltham, MA 02452 USA. [Qin, Lizeng] Harvard Univ, Sch Med, Boston, MA USA. [Mullen, Gary John] East Carolina Anesthesia Associates PLLC, Greenville, NC USA. [Ladd, Diane] W Virginia Univ, Sch Nursing, Morgantown, WV 26506 USA. [George, Edward] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA. RP Ladd, D (reprint author), Resp Mot Inc, 411 Waverley Oaks Rd,Suite 150, Waltham, MA 02452 USA. EM cjvoscopoulos@yahoo.com; marshall.macnabb@respiratorymotion.com; jordan.brayanov@respiratorymotion.com; lizeng.qin@gmail.com; jfreeman@respiratorymotion.com; dladd@respiratorymotion.com NR 19 TC 10 Z9 10 U1 2 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1387-1307 EI 1573-2614 J9 J CLIN MONIT COMPUT JI J. Clin. Monitor. Comp. PD APR PY 2015 VL 29 IS 2 BP 223 EP 230 DI 10.1007/s10877-014-9596-0 PG 8 WC Anesthesiology SC Anesthesiology GA CF7NE UT WOS:000352742400005 PM 25037938 ER PT J AU Kulich, R Berna, C Backstrom, J Mao, J AF Kulich, R. Berna, C. Backstrom, J. Mao, J. TI The use of a commonly-used digital monitoring device as a post treatment activity measure to encourage function after structured opioid tapering, a case report SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Kulich, R.; Berna, C.; Backstrom, J.; Mao, J.] Massachusetts Gen Hosp, Ctr Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2015 VL 16 IS 4 SU 1 MA 476 BP S95 EP S95 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF7PK UT WOS:000352748600377 ER PT J AU Maeda, Y Kettner, N Kim, J Cina, S Malatesta, C Gerber, J McManus, C Libby, A Ong-Sutherland, R Mezzacappa, P Morse, L Audette, J Napadow, V AF Maeda, Y. Kettner, N. Kim, J. Cina, S. Malatesta, C. Gerber, J. McManus, C. Libby, A. Ong-Sutherland, R. Mezzacappa, P. Morse, L. Audette, J. Napadow, V. TI Cortical thickness increase following acupuncture therapy is associated with symptom improvement in idiopathic hand pain SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Maeda, Y.; Kettner, N.; Kim, J.; Cina, S.; Malatesta, C.; Gerber, J.; McManus, C.; Libby, A.; Ong-Sutherland, R.; Mezzacappa, P.; Morse, L.; Audette, J.; Napadow, V.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2015 VL 16 IS 4 SU 1 MA 536 BP S110 EP S110 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF7PK UT WOS:000352748600437 ER PT J AU Schreiber, K Loggia, M Cahalan, C Napadow, V Edwards, R AF Schreiber, K. Loggia, M. Cahalan, C. Napadow, V. Edwards, R. TI Modulation of experimental and clinical pain by distraction in fibromyalgia patients and controls SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Schreiber, K.; Loggia, M.; Cahalan, C.; Napadow, V.; Edwards, R.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2015 VL 16 IS 4 SU 1 MA 211 BP S28 EP S28 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF7PK UT WOS:000352748600113 ER PT J AU Stevenson, K Collins, E Ebert, J Johnson, D Schiffman, J Blair, T AF Stevenson, K. Collins, E. Ebert, J. Johnson, D. Schiffman, J. Blair, T. TI Establishment of a controlled substance advisory review consult process for patients on chronic opioid therapy SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Stevenson, K.; Collins, E.; Ebert, J.; Johnson, D.; Schiffman, J.; Blair, T.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2015 VL 16 IS 4 SU 1 MA 245 BP S37 EP S37 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF7PK UT WOS:000352748600147 ER PT J AU Taylor, N Pei, J Van Dort, C Brown, E Solt, K AF Taylor, N. Pei, J. Van Dort, C. Brown, E. Solt, K. TI DREADD activation of dopaminergic and glutamatergic neurons in the periaquaductal gray produces differing analgesic responses SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Taylor, N.; Pei, J.; Van Dort, C.; Brown, E.; Solt, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2015 VL 16 IS 4 SU 1 MA 325 BP S57 EP S57 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF7PK UT WOS:000352748600227 ER PT J AU Voscopoulos, C Ladd, D George, E AF Voscopoulos, C. Ladd, D. George, E. TI The use of a non-invasive respiratory volume monitor to identify patients at high-risk for opioid-induced respiratory depression for a low-dose opioid regimen in the PACU SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Voscopoulos, C.; Ladd, D.; George, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2015 VL 16 IS 4 SU 1 MA 129 BP S8 EP S8 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF7PK UT WOS:000352748600031 ER PT J AU Salley, CG Hewitt, LL Patenaude, AF Vasey, MW Yeates, KO Gerhardt, CA Vannatta, K AF Salley, Christina G. Hewitt, Larissa L. Patenaude, Andrea F. Vasey, Michael W. Yeates, Keith O. Gerhardt, Cynthia A. Vannatta, Kathryn TI Temperament and Social Behavior in Pediatric Brain Tumor Survivors and Comparison Peers SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE brain tumor; pediatric; social; temperament ID QUALITY-OF-LIFE; EXECUTIVE ATTENTION; EFFORTFUL CONTROL; CANCER-PATIENTS; SELF-REGULATION; CHILDREN; CHILDHOOD; ADJUSTMENT; EMOTIONALITY; PERSONALITY AB Objective To examine the role of temperament (i.e., surgency/positive affect, negative affect, and effortful control) in the social behavior of pediatric brain tumor survivors and comparison classmates. Methods Parent-, peer-, and self-report data were collected for 75 children after treatment for a brain tumor, and 67 comparison classmates. Tests of mediation and moderated mediation were run to examine whether effortful control accounted for group differences in social behavior and whether this indirect effect was moderated by surgency/positive or negative affectivity. Results Peers described survivors as lower in Leadership-popularity and higher in Sensitivity-isolation and victimization than comparison classmates. Parent and self-report of surgency/positive affect revealed survivors were lower on this dimension. Survivors were rated by parents as demonstrating less effortful control. Effortful control did not consistently account for group differences in social behavior. There was limited evidence of moderated mediation. Conclusions Research on the implications of potential changes in temperament following treatment is warranted. C1 [Salley, Christina G.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Hewitt, Larissa L.; Patenaude, Andrea F.] Dana Farber Canc Inst, Boston, MA USA. [Patenaude, Andrea F.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Vasey, Michael W.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Yeates, Keith O.; Gerhardt, Cynthia A.; Vannatta, Kathryn] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Yeates, Keith O.; Gerhardt, Cynthia A.; Vannatta, Kathryn] Nationwide Childrens Hosp, Res Inst, Ctr Biobehav Hlth, Columbus, OH USA. RP Salley, CG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM salleyc@mskcc.org OI Yeates, Keith/0000-0001-7680-2892 FU American Cancer Society [RSGPB-03-098-01-PBP]; National Cancer Institute [R03 CA138122-02] FX This work was supported by awards from the American Cancer Society (RSGPB-03-098-01-PBP) and the National Cancer Institute (R03 CA138122-02). NR 53 TC 6 Z9 6 U1 6 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 EI 1465-735X J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD APR PY 2015 VL 40 IS 3 SI SI BP 297 EP 308 DI 10.1093/jpepsy/jsu083 PG 12 WC Psychology, Developmental SC Psychology GA CF3YT UT WOS:000352485700004 PM 25287068 ER PT J AU Ayala, D Garcia, J Sanchez-Reilly, S AF Ayala, D. Garcia, J. Sanchez-Reilly, S. TI Myths, Beliefs and Their Effect on Pain Control on the Elderly SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Ayala, D.; Garcia, J.; Sanchez-Reilly, S.] UTHSCSA, San Antonio, TX USA. [Ayala, D.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Garcia, J.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B171 BP S152 EP S152 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900424 ER PT J AU Berry, S Zullo, AR Lee, Y Kiel, D Dosa, D Mor, V AF Berry, S. Zullo, A. R. Lee, Y. Kiel, D. Dosa, D. Mor, V. TI Incidence of hip fracture in US nursing homes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Berry, S.; Kiel, D.] Hebrew SeniorLife, IFAR, Boston, MA USA. [Berry, S.; Kiel, D.] BIDMC, Boston, MA USA. [Zullo, A. R.; Lee, Y.; Dosa, D.; Mor, V.] Brown Univ, Providence, RI 02912 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B39 BP S104 EP S104 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900292 ER PT J AU Boockvar, KS Guerrero, V Torres, J Beckford, K Smyth, C Wen, L Teresi, J Inouye, S AF Boockvar, K. S. Guerrero, V. Torres, J. Beckford, K. Smyth, C. Wen, L. Teresi, J. Inouye, S. TI Characteristics of patients receiving a multicomponent delirium-prevention intervention in the nursing home setting SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Boockvar, K. S.] James J Peters VA Med Ctr, Bronx, NY USA. [Boockvar, K. S.; Guerrero, V.; Torres, J.; Beckford, K.] Jewish Home Lifecare, New York, NY USA. [Smyth, C.; Wen, L.] Optum CarePlus, Eden Prairie, MN USA. [Teresi, J.] Hebrew Home, Bronx, NY USA. [Teresi, J.] Columbia Univ, New York, NY USA. [Inouye, S.] Hebrew SeniorLife, Boston, MA USA. [Inouye, S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B79 BP S119 EP S119 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900332 ER PT J AU Branch-Elliman, W Snyderman, D Wilson, B Carter, R Heath, B Mody, L Moehring, R Crnich, C Schmader, K Jump, R AF Branch-Elliman, W. Snyderman, D. Wilson, B. Carter, R. Heath, B. Mody, L. Moehring, R. Crnich, C. Schmader, K. Jump, R. TI Preliminary Outcomes from an Educational Intervention to Promote Antimicrobial Stewardship and Improve the Care of Older Adults with Infections SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Branch-Elliman, W.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Branch-Elliman, W.] Univ Colorado, Sch Med, Denver, CO USA. [Snyderman, D.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Wilson, B.; Carter, R.; Heath, B.; Jump, R.] Louis Stokes Cleveland VAMC, Cleveland, OH USA. [Carter, R.; Jump, R.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Mody, L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Mody, L.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Moehring, R.; Schmader, K.] Duke Univ, Durham, NC USA. [Moehring, R.; Schmader, K.] Durham VAMC, Durham, NC USA. [Crnich, C.] Univ Wisconsin, Madison, WI USA. [Crnich, C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A106 BP S54 EP S54 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900152 ER PT J AU Campbell, A Coley, K Thorpe, C Corbo, J McGivney, M Klatt, P Zaharoff, J Cox-Vance, L Sakely, H AF Campbell, A. Coley, K. Thorpe, C. Corbo, J. McGivney, M. Klatt, P. Zaharoff, J. Cox-Vance, L. Sakely, H. TI The impact of pharmacists caring for geriatric patients across the healthcare continuum on the identification, resolution, and prevention of drug therapy problems: A subset of the PIVOTS (Pharmacist-led Interventions on the Transitions of Seniors) Group SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Campbell, A.; Corbo, J.; Klatt, P.; Cox-Vance, L.; Sakely, H.] UPMC St Margaret, Pittsburgh, PA USA. [Coley, K.; Thorpe, C.; McGivney, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Thorpe, C.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Zaharoff, J.] Presbyterian SeniorCare, Oakmont, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA D83 BP S265 EP S265 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900745 ER PT J AU Chen, P Sun, DM Boockvar, KS Hung, W AF Chen, P. Sun, D. M. Boockvar, K. S. Hung, W. TI Geriatrics Case Teleconference for Rural Healthcare Professionals: Evaluation of Barriers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Chen, P.; Boockvar, K. S.; Hung, W.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Sun, D. M.; Boockvar, K. S.; Hung, W.] James J Peters VA Med Ctr, GRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A102 BP S53 EP S53 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900148 ER PT J AU Cheng, J Castle, S Blanchard, E Ines, E Roberts, C Morey, MC Hall, K Deberry, J Valencia-Rodrigo, W Steinbrenner, G Katzel, L Giffuni, J Kopp, T Cammarata, H Lee, CC AF Cheng, J. Castle, S. Blanchard, E. Ines, E. Roberts, C. Morey, M. C. Hall, K. Deberry, J. Valencia-Rodrigo, W. Steinbrenner, G. Katzel, L. Giffuni, J. Kopp, T. Cammarata, H. Lee, C. C. TI Integration of the FallProof Balance Program into the Gerofit Veterans Fitness Program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Cheng, J.; Castle, S.; Blanchard, E.; Ines, E.; Roberts, C.; Lee, C. C.] VA Greater Los Angeles, GRECC, Los Angeles, CA USA. [Morey, M. C.; Hall, K.; Deberry, J.] VHA Durham, GRECC, Durham, NC USA. [Valencia-Rodrigo, W.] VHA Miami, GRECC, Miami, FL USA. [Steinbrenner, G.; Katzel, L.; Giffuni, J.] VHA Baltimore, GRECC, Baltimore, MD USA. [Kopp, T.; Cammarata, H.] VAMC Canandaigua, Canandaigua, NY 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA D65 BP S258 EP S259 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900727 ER PT J AU Cummins, J Lyketsos, C Tariot, PN Peskind, ER Nguyen, U Knowles, N Shin, P Siffert, J AF Cummins, J. Lyketsos, C. Tariot, P. N. Peskind, E. R. Nguyen, U. Knowles, N. Shin, P. Siffert, J. TI Dextromethorphan/Quinidine (AVP-923) Efficacy and Safety for Treatment of Agitation in Persons With Alzheimer's Disease: Results From a Phase 2 Study (NCT01584440) SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Cummins, J.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA. [Lyketsos, C.] Johns Hopkins Med, Baltimore, MD USA. [Tariot, P. N.] Banner Alzheimers Inst, Phoenix, AZ USA. [Peskind, E. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nguyen, U.; Knowles, N.; Shin, P.; Siffert, J.] Avanir Pharmaceut Inc, Aliso Viejo, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A42 BP S32 EP S32 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900088 ER PT J AU Dharia, T Jang, M Schwab, E Ang, K AF Dharia, T. Jang, M. Schwab, E. Ang, K. TI Proton Pump Inhibitor (PPI) Tapering - A Primary Care Difficulty SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Dharia, T.; Jang, M.; Schwab, E.] Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. [Dharia, T.; Jang, M.; Schwab, E.; Ang, K.] Philadelphia VA Med Ctr, Div Geriatr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA C132 BP S206 EP S206 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900578 ER PT J AU Emami, S Franco, E AF Emami, S. Franco, E. TI Which Came First; Confusion or Consolidation? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Emami, S.; Franco, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA C216 BP S235 EP S235 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900662 ER PT J AU Fung, CH Alessi, C Truong, C Josephson, K Hays, R Col, N Patterson, E Martin, J AF Fung, C. H. Alessi, C. Truong, C. Josephson, K. Hays, R. Col, N. Patterson, E. Martin, J. TI Patient-provider communication about sleep apnea: Results from focus groups with older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Fung, C. H.; Alessi, C.; Truong, C.; Josephson, K.; Martin, J.] VA Greater Los Angeles, Los Angeles, CA USA. [Fung, C. H.; Alessi, C.; Truong, C.; Hays, R.; Martin, J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Col, N.] Univ So Maine, Portland, ME 04103 USA. [Patterson, E.] Ohio State Univ, Columbus, OH 43210 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A140 BP S66 EP S66 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900186 ER PT J AU Gordon, SE Khan, AM Mathur, J Schutzbank, AM Judge, D Haymont, C Vinck, P Levine, M Perrin, E Fernandopulle, R AF Gordon, S. E. Khan, A. M. Mathur, J. Schutzbank, A. M. Judge, D. Haymont, C. Vinck, P. Levine, M. Perrin, E. Fernandopulle, R. TI A New Model of Geriatric Primary Care: Iora Health SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Gordon, S. E.; Khan, A. M.; Mathur, J.; Schutzbank, A. M.; Judge, D.; Haymont, C.; Vinck, P.; Levine, M.; Perrin, E.; Fernandopulle, R.] Iora Hlth, Cambridge, MA USA. [Judge, D.; Fernandopulle, R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gordon, S. E.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Schutzbank, A. M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Haymont, C.; Levine, M.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Khan, A. M.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A180 BP S80 EP S80 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900226 ER PT J AU Greene, M Hessol, N Perissinotto, C Marcotte, T Hutton-Parrott, A Zepf, R Foreman, C Whirry, R Gandhi, M John, M AF Greene, M. Hessol, N. Perissinotto, C. Marcotte, T. Hutton-Parrott, A. Zepf, R. Foreman, C. Whirry, R. Gandhi, M. John, M. TI Loneliness is Associated with Functional Impairment and Health-Related Quality of Life in Older HIV-Positive Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Greene, M.; Hessol, N.; Perissinotto, C.; Marcotte, T.; Hutton-Parrott, A.; Zepf, R.; Foreman, C.; Gandhi, M.; John, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Greene, M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Whirry, R.] Robert Whirry & Associates, Los Angeles, CA 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B176 BP S154 EP S154 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900429 ER PT J AU Greene, M Cenzer, IS Ahalt, C Williams, B AF Greene, M. Cenzer, I. Stijacic Ahalt, C. Williams, B. TI Older Jail Inmates Experience Early Onset of Geriatric Conditions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Greene, M.; Cenzer, I. Stijacic; Ahalt, C.; Williams, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Greene, M.; Cenzer, I. Stijacic; Williams, B.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B94 BP S124 EP S124 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900347 ER PT J AU Hagiwara, Y Ross, J Reilly, A Lee, S Sanchez-Reilly, S AF Hagiwara, Y. Ross, J. Reilly, A. Lee, S. Sanchez-Reilly, S. TI Tough Conversations: Training Medical Students to Lead Family Meetings SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Hagiwara, Y.; Ross, J.; Sanchez-Reilly, S.] UT Hlth Sci Ctr San Antonio, Geriatr Gerontol & Palliat Med, San Antonio, TX USA. [Ross, J.; Reilly, A.; Lee, S.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA P15 BP S6 EP S6 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900016 ER PT J AU Hoffman, L Jenkins, A Masoudi, F Magid, DJ Sepucha, K Kutner, JS Bekelman, D Lowery, C Matlock, DD AF Hoffman, L. Jenkins, A. Masoudi, F. Magid, D. J. Sepucha, K. Kutner, J. S. Bekelman, D. Lowery, C. Matlock, D. D. TI Preferences around dying among patients with ICDs SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Hoffman, L.; Jenkins, A.; Masoudi, F.; Kutner, J. S.; Matlock, D. D.] Univ Colorado, Sch Med, Aurora, CO USA. [Masoudi, F.; Magid, D. J.; Bekelman, D.; Matlock, D. D.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Magid, D. J.; Lowery, C.] Kaiser Permanente Colorado, Inst Hlth Rse, Denver, CO USA. [Sepucha, K.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Sepucha, K.] Harvard Univ, Sch Med, Boston, MA USA. [Bekelman, D.] Denver Vet Affairs Hosp, Denver, CO 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B45 BP S106 EP S106 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900298 ER PT J AU Horney, C Capp, R Burke, RE Boxer, RS AF Horney, C. Capp, R. Burke, R. E. Boxer, R. S. TI Shorter Length of Hospital Stay Associated with Early Readmissions from Post-Acute Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Horney, C.; Boxer, R. S.] Univ Colorado, Dept Med, Div Geriatr Med, Aurora, CO USA. [Capp, R.] Univ Colorado, Dept Emergency Med, Aurora, CO USA. [Burke, R. E.] Denver VA Med Ctr, Med Serv, Hosp Med Sect, Denver, CO USA. [Burke, R. E.] Univ Colorado, Dept Med, Div Gen Internal Med, Aurora, CO 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B25 BP S99 EP S99 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900278 ER PT J AU Hsu, A Henderson, JT Harper, CC Sawaya, GF AF Hsu, A. Henderson, J. T. Harper, C. C. Sawaya, G. F. TI Pelvic examinations in older women: practices and beliefs of US obstetrician-gynecologists SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Hsu, A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Henderson, J. T.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Harper, C. C.; Sawaya, G. F.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B164 BP S150 EP S150 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900417 ER PT J AU Jang, M Schwab, E AF Jang, M. Schwab, E. TI Dementia and the "Great Imitator": Neurosyphilis in a Veteran Presenting with Delirium SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Jang, M.; Schwab, E.] Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. [Jang, M.; Schwab, E.] Philadelphia Vet Affairs Med Ctr, Div Geriatr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A26 BP S26 EP S27 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900072 ER PT J AU Kennelty, K Troller, P Deniger, A Doh, J Mirr, J Dattalo, M Kind, A AF Kennelty, K. Troller, P. Deniger, A. Doh, J. Mirr, J. Dattalo, M. Kind, A. TI Prevalence of Medication Discrepancies Post-Discharge by Community Pharmacy Type for Older Adult Patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Kennelty, K.; Dattalo, M.; Kind, A.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Troller, P.; Deniger, A.; Dattalo, M.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Kennelty, K.; Doh, J.; Mirr, J.; Kind, A.] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA C151 BP S212 EP S213 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900597 ER PT J AU Kilpatrick, L Williams, B Harada, C AF Kilpatrick, L. Williams, B. Harada, C. TI Reflections on Frailty from First Year Internal Medicine SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Kilpatrick, L.] Baylor Scott & White, Temple, TX USA. [Williams, B.; Harada, C.] Univ Alabama Birmingham, Birmingham, AL USA. [Williams, B.; Harada, C.] Birmingham VAMC, Birmingham, AL 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A99 BP S51 EP S52 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900145 ER PT J AU Kodela, J Heng, M Eagen, C Vrahas, M Weaver, M Harris, M Javedan, H AF Kodela, J. Heng, M. Eagen, C. Vrahas, M. Weaver, M. Harris, M. Javedan, H. TI Mini-Cog as a Predictor of Outcomes in Elder Fracture Patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Kodela, J.] Univ New England, Coll Osteopath Med, Biddeford, ME USA. [Eagen, C.; Weaver, M.; Harris, M.; Javedan, H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Heng, M.; Vrahas, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA D132 BP S282 EP S282 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900794 ER PT J AU Maggiore, R Callahan, K Parker, I Tooze, J Hsu, T Klepin, H AF Maggiore, R. Callahan, K. Parker, I. Tooze, J. Hsu, T. Klepin, H. TI Cancer Care Training Content of US Geriatric Medicine Fellowship Programs: A Survey of Geriatrics Fellowship Program Directors SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Maggiore, R.] Portland VA Med Ctr, Portland, OR USA. [Callahan, K.; Tooze, J.; Klepin, H.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Parker, I.] ElderCare Mediat Solut, San Diego, CA USA. [Hsu, T.] Ottawa Hosp, Ctr Canc, Ottawa, ON, Canada. 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A107 BP S54 EP S55 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900153 ER PT J AU Makris, UE Pugh, M Alvarez, CA Mortensen, EM AF Makris, U. E. Pugh, M. Alvarez, C. A. Mortensen, E. M. TI Exposure to High Risk Medications is Associated with Worse Outcomes in Older Veterans with Chronic Pain SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Makris, U. E.; Alvarez, C. A.; Mortensen, E. M.] Univ Texas SW Med Ctr Dallas, Internal Med, Dallas, TX 75390 USA. [Makris, U. E.; Mortensen, E. M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Pugh, M.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pugh, M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Alvarez, C. A.] Texas Tech Univ, Hlth Sci Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A154 BP S71 EP S71 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900200 ER PT J AU McCaskill, GM Bowen, PG Leeper, P Burgio, KL Clay, OJ AF McCaskill, G. M. Bowen, P. G. Leeper, J. Burgio, K. L. Clay, O. J. TI Predicting Aerobic Activity among Older African Americans with Chronic Conditions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [McCaskill, G. M.] Birmingham VAMC, Birmingham, AL USA. [Bowen, P. G.; Burgio, K. L.; Clay, O. J.] Univ Alabama Birmingham, Birmingham, AL USA. [Leeper, J.] Univ Alabama, Tuscaloosa, AL 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A130 BP S63 EP S63 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900176 ER PT J AU McElwain, L Brown, C Fix, K Waite, C Booth, KA Markland, AD AF McElwain, L. Brown, C. Fix, K. Waite, C. Booth, K. A. Markland, A. D. TI Documentation and Accessibility of Advance Care Planning Discussions for Home-Based Primary Care Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [McElwain, L.; Brown, C.; Fix, K.; Booth, K. A.; Markland, A. D.] Univ Alabama Birmingham, Birmingham, AL USA. [McElwain, L.; Fix, K.; Waite, C.] Birmingham VA Med Ctr, Birmingham, AL USA. [Brown, C.; Booth, K. A.; Markland, A. D.] Birmingham Atlanta GRECC, Birmingham, AL 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA C75 BP S186 EP S186 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900521 ER PT J AU Miura, L Black, A Franklin, S Pruitt, C Goodlin, S AF Miura, L. Black, A. Franklin, S. Pruitt, C. Goodlin, S. TI Reaching Rural Veterans with Dementia through Telehealth: the Rural Collaborative Dementia Program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Miura, L.; Black, A.; Franklin, S.; Pruitt, C.; Goodlin, S.] Portland VA Med Ctr, Med, Portland, OR USA. [Miura, L.; Goodlin, S.] Oregon Hlth & Sci Univ, Med, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A132 BP S63 EP S64 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900178 ER PT J AU Nebolisa, BC Isenberg, EE Domeier, RM Swor, R Hendry, PL Peak, DA Rathlev, NK Jones, JS Lee, DC McLean, SA Platts-Mills, TF AF Nebolisa, B. C. Isenberg, E. E. Domeier, R. M. Swor, R. Hendry, P. L. Peak, D. A. Rathlev, N. K. Jones, J. S. Lee, D. C. McLean, S. A. Platts-Mills, T. F. TI Post-Traumatic Stress Disorder among Elderly Motor Vehicle Collision Victims Receiving Care in the Emergency Department SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [McLean, S. A.; Platts-Mills, T. F.] Univ N Carolina, Emergency Med, Chapel Hill, NC USA. [Domeier, R. M.] St Joseph Mercy Hlth Syst, Emergency Med, Ypsilanti, MI USA. [Swor, R.] William Beaumont Hosp, Emergency Med, Royal Oak, MI 48072 USA. [Hendry, P. L.] Univ Florida, Coll Med, Emergency Med, Jacksonville, FL USA. [Peak, D. A.] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02114 USA. [Rathlev, N. K.] Baysate Med Ctr, Emergency Med, Springfield, MA USA. [Jones, J. S.] Spectrum Hlth, Emergency Med, Grand Rapids, MI USA. [Lee, D. C.] N Shore Univ Hosp, Emergency Med, Manhasset, NY USA. [McLean, S. A.] Univ N Carolina, Anesthesiol, Chapel Hill, NC USA. [Nebolisa, B. C.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Isenberg, E. E.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA D32 BP S247 EP S247 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900695 ER PT J AU Ngo, Q Shi, Y Shu, Z Kamat, A AF Ngo, Q. Shi, Y. Shu, Z. Kamat, A. TI Age-Related Alterations in Expression of Key Regulators of Hepatic Lipid Metabolism in a Non-Human Primate Model SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Ngo, Q.; Shi, Y.; Shu, Z.; Kamat, A.] Univ Texas Hlth Sci Ctr San Antonio, Med, San Antonio, TX 78229 USA. [Shi, Y.; Shu, Z.; Kamat, A.] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B55 BP S110 EP S110 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900308 ER PT J AU Noble, S Sanchez-Reilly, S Ross, J AF Noble, S. Sanchez-Reilly, S. Ross, J. TI Facebook as a Resource for Informal Caregivers of Dementia Patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Noble, S.; Sanchez-Reilly, S.; Ross, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Noble, S.; Sanchez-Reilly, S.; Ross, J.] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA P6 BP S2 EP S3 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900007 ER PT J AU Poon, LH Nigro, S Wittkop, E Lee, AJ AF Poon, L. H. Nigro, S. Wittkop, E. Lee, A. J. TI Impact of a geriatric pharmacist conducted hospital discharge follow-up program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Poon, L. H.; Nigro, S.; Lee, A. J.] San Francisco VA Med Ctr, Pharm, San Francisco, CA USA. [Poon, L. H.; Lee, A. J.] Univ Pacific, Sch Pharm & Hlth Sci, Stockton, CA 95211 USA. [Wittkop, E.] VA Northern Calif Hlth Care Syst, Pharm, Martinez, CA 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A174 BP S78 EP S78 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900220 ER PT J AU Rothrock, AG Bearden, D Simmons, E Sawyer, P Brown, C Flood, K AF Rothrock, A. G. Bearden, D. Simmons, E. Sawyer, P. Brown, C. Flood, K. TI Safe Mobility for Older Adults in Acute Care Settings: Simulation Training for Interprofessional Providers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Rothrock, A. G.; Bearden, D.; Simmons, E.; Sawyer, P.; Brown, C.; Flood, K.] Univ Alabama Birmingham, Birmingham, AL USA. [Brown, C.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA A79 BP S45 EP S45 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900125 ER PT J AU Stephens, C Halifax, E Bui, N Lee, SJ Harrington, C Shim, J Ritchie, C AF Stephens, C. Halifax, E. Bui, N. Lee, S. J. Harrington, C. Shim, J. Ritchie, C. TI The Perceived Influence of Family on Nursing Home Resident ER Transfers and Potential Role for Palliative Care and Emerging Health Technologies SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Lee, S. J.] Univ Calif San Francisco, Geriatr Palliat & Extended Care, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Stephens, C.; Halifax, E.; Bui, N.] Univ Calif San Francisco, Community Hlth Syst, San Francisco, CA 94143 USA. [Harrington, C.; Shim, J.] Univ Calif San Francisco, Social & Behav Sci, San Francisco, CA 94143 USA. [Ritchie, C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA C135 BP S207 EP S207 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900581 ER PT J AU Stephens, C Halifax, E Bui, N Shim, J Ritchie, C Harrington, C Lee, SJ AF Stephens, C. Halifax, E. Bui, N. Shim, J. Ritchie, C. Harrington, C. Lee, S. J. TI "They don't trust us": The Influence of Perceptions of Inadequate Nursing Home Care on ER Transfers and Potential Role for Emerging Health Technologies SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Lee, S. J.] UC San Francisco, San Francisco VA Med Ctr, Geriatr Palliat & Extended Care, San Francisco, CA USA. [Stephens, C.; Halifax, E.; Bui, N.] Univ Calif San Francisco, Community Hlth Syst, San Francisco, CA 94143 USA. [Shim, J.; Harrington, C.] Univ Calif San Francisco, Social & Behav Sci, San Francisco, CA 94143 USA. [Ritchie, C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B98 BP S125 EP S126 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900351 ER PT J AU Uy, N Moye, J Anaya, D Naik, AD AF Uy, N. Moye, J. Anaya, D. Naik, A. D. TI The Effects of Age, Education, and Treatment on Physical, Sexual and Body Concern Symptoms among Multimorbid, Colorectal Cancer Survivors SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Uy, N.; Anaya, D.; Naik, A. D.] Michael E DeBakey VA Med Ctr, Hlth Serv Res, Houston, TX USA. [Uy, N.; Naik, A. D.] Baylor Coll Med, Med, Houston, TX 77030 USA. [Moye, J.] VA Boston Healthcare Syst, Geriatr Mental Hlth, Boston, MA USA. [Moye, J.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Anaya, D.] Baylor Coll Med, Surg, Houston, TX 77030 USA. RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B169 BP S152 EP S152 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900422 ER PT J AU Wright, RM Rossi, MI Marcum, Z AF Wright, R. M. Rossi, M. I. Marcum, Z. TI The Geriatric Pharmacology QI Project SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Rossi, M. I.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Wright, R. M.; Rossi, M. I.; Marcum, Z.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA C111 BP S199 EP S199 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900557 ER PT J AU Wright, RM Rossi, MI AF Wright, R. M. Rossi, M. I. TI Milestones for an Internal Medicine Residency Geriatrics Rotation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Wright, R. M.; Rossi, M. I.] Univ Pittsburgh, Med Geriatr, Pittsburgh, PA USA. [Rossi, M. I.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA B70 BP S115 EP S116 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900323 ER PT J AU Zullo, AR Lee, Y Mor, V Daiello, L Komaiko, K Boscardin, WJ Steinman, M AF Zullo, A. R. Lee, Y. Mor, V. Daiello, L. Komaiko, K. Boscardin, W. J. Steinman, M. TI Beta Blocker Use Among United States Nursing Home Residents After Myocardial Infarction: A National Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society (AGS) CY MAY 10-17, 2015 CL National Harbor, MD SP Amer Geriatr Soc C1 [Komaiko, K.; Boscardin, W. J.; Steinman, M.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Komaiko, K.; Boscardin, W. J.; Steinman, M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Zullo, A. R.; Lee, Y.; Mor, V.; Daiello, L.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 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 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2015 VL 63 SU 1 SI SI MA P19 BP S7 EP S7 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CF5EL UT WOS:000352578900020 ER PT J AU Koh, WJ Greer, BE Abu-Rustum, NR Apte, SM Campos, SM Cho, KR Chu, C Cohn, D Crispens, MA Dorigo, O Eifel, PJ Fisher, CM Frederick, P Gaffney, DK Han, E Huh, WK Lurain, JR Mutch, D Fader, AN Remmenga, SW Reynolds, RK Teng, N Tillmanns, T Valea, FA Yashar, CM McMillian, NR Scavone, JL AF Koh, Wui-Jin Greer, Benjamin E. Abu-Rustum, Nadeem R. Apte, Sachin M. Campos, Susana M. Cho, Kathleen R. Chu, Christina Cohn, David Crispens, Marta Ann Dorigo, Oliver Eifel, Patricia J. Fisher, Christine M. Frederick, Peter Gaffney, David K. Han, Ernest Huh, Warner K. Lurain, John R., III Mutch, David Fader, Amanda Nickles Remmenga, Steven W. Reynolds, R. Kevin Teng, Nelson Tillmanns, Todd Valea, Fidel A. Yashar, Catheryn M. McMillian, Nicole R. Scavone, Jillian L. TI Cervical Cancer, Version 2.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID SENTINEL LYMPH-NODE; ABDOMINAL RADICAL TRACHELECTOMY; GYNECOLOGIC-ONCOLOGY-GROUP; HUMAN-PAPILLOMAVIRUS INFECTION; FERTILITY-SPARING SURGERY; SQUAMOUS-CELL CARCINOMA; FALSE-NEGATIVE RATE; UTERINE CERVIX; UNITED-STATES; YOUNG-WOMEN AB The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches. C1 [Koh, Wui-Jin] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Greer, Benjamin E.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Abu-Rustum, Nadeem R.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Apte, Sachin M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Campos, Susana M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cho, Kathleen R.; Reynolds, R. Kevin] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chu, Christina] Fox Chase Canc Ctr, Philadelphia, PA USA. [Cohn, David] Ohio State Univ, Comprehens Canc Ctr James Canc Hosp, Columbus, OH 43210 USA. [Cohn, David] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dorigo, Oliver; Teng, Nelson] Stanford Canc Inst, Stanford, CA USA. [Eifel, Patricia J.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Fisher, Christine M.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Frederick, Peter] Roswell Pk Canc Inst, Buffalo, NY USA. [Gaffney, David K.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Han, Ernest] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Huh, Warner K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Lurain, John R., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Mutch, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Mutch, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fader, Amanda Nickles] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Remmenga, Steven W.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Tillmanns, Todd] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Valea, Fidel A.] Duke Canc Inst, Durham, NC USA. [Yashar, Catheryn M.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [McMillian, Nicole R.; Scavone, Jillian L.] Natl Comprehens Canc Network, Ft Washington, MD USA. RP Koh, WJ (reprint author), Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. FU Eisai; Bristol-Myers Squibb; Genentech BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 65 TC 42 Z9 48 U1 1 U2 8 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2015 VL 13 IS 4 BP 395 EP 404 PG 10 WC Oncology SC Oncology GA CG0NB UT WOS:000352962200005 PM 25870376 ER PT J AU Stein, BL Gotlib, J Arcasoy, M Nguyen, MH Shah, N Moliterno, A Jamieson, C Pollyea, DA Scott, B Wadleigh, M Levine, R Komrokji, R Klisovic, R Gundabolu, K Kropf, P Wetzler, M Oh, ST Ribeiro, R Paschal, R Mohan, S Podoltsev, N Prchal, J Talpaz, M Snyder, D Verstovsek, S Mesa, RA AF Stein, Brady L. Gotlib, Jason Arcasoy, Murat Nguyen, Marie Huong Shah, Neil Moliterno, Alison Jamieson, Catriona Pollyea, Daniel A. Scott, Bart Wadleigh, Martha Levine, Ross Komrokji, Rami Klisovic, Rebecca Gundabolu, Krishna Kropf, Patricia Wetzler, Meir Oh, Stephen T. Ribeiro, Raul Paschal, Rita Mohan, Sanjay Podoltsev, Nikolai Prchal, Josef Talpaz, Moshe Snyder, David Verstovsek, Srdan Mesa, Ruben A. TI Historical Views, Conventional Approaches, and Evolving Management Strategies for Myeloproliferative Neoplasms SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID INTERNATIONAL WORKING GROUP; HEMATOPOIETIC-CELL TRANSPLANTATION; DEFINED ESSENTIAL THROMBOCYTHEMIA; ORGANIZATION DIAGNOSTIC-CRITERIA; POLYCYTHEMIA-VERA; PRIMARY MYELOFIBROSIS; CALRETICULIN MUTATIONS; MYELOID METAPLASIA; SCORING SYSTEM; JAK2 INHIBITOR AB The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for hematologists/oncologists, and are discussed in this article. C1 [Stein, Brady L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gotlib, Jason] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Arcasoy, Murat] Duke Univ, Duke Canc Inst, Durham, NC USA. [Nguyen, Marie Huong; Talpaz, Moshe] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Shah, Neil] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Moliterno, Alison] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Jamieson, Catriona] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA USA. [Pollyea, Daniel A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Scott, Bart] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Levine, Ross] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Komrokji, Rami] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Komrokji, Rami] Res Inst, Tampa, FL USA. [Klisovic, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Gundabolu, Krishna] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Kropf, Patricia] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Oh, Stephen T.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Ribeiro, Raul] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Paschal, Rita] Univ Alabama Birmingham, Birmingham, AL USA. [Mohan, Sanjay] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Podoltsev, Nikolai] Yale Univ, Sch Med, New Haven, CT USA. [Prchal, Josef] Univ Utah, Salt Lake City, UT USA. [Snyder, David] City Hope Canc Ctr, Los Angeles, CA USA. [Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Mesa, Ruben A.] Mayo Clin Canc Ctr, Scottsdale, AZ 85259 USA. RP Mesa, RA (reprint author), Mayo Clin Canc Ctr, 13400 East Shea Blvd, Scottsdale, AZ 85259 USA. EM mesa.ruben@mayo.edu FU NCI NIH HHS [P30 CA016672] NR 111 TC 10 Z9 10 U1 1 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2015 VL 13 IS 4 BP 424 EP 434 PG 11 WC Oncology SC Oncology GA CG0NB UT WOS:000352962200008 PM 25870379 ER PT J AU Gradishar, WJ Anderson, BO Balassanian, R Blair, SL Burstein, HJ Cyr, A Elias, AD Farrar, WB Forero, A Giordano, SH Goetz, M Goldstein, LJ Hudis, CA Isakoff, SJ Marcom, PK Mayer, IA McCormick, B Moran, M Patel, SA Pierce, LJ Reed, EC Salerno, KE Schwartzberg, LS Smith, KL Smith, ML Soliman, H Somlo, G Telli, M Ward, JH Shead, DA Kumar, R AF Gradishar, William J. Anderson, Benjamin O. Balassanian, Ron Blair, Sarah L. Burstein, Harold J. Cyr, Amy Elias, Anthony D. Farrar, William B. Forero, Andres Giordano, Sharon Hermes Goetz, Matthew Goldstein, Lori J. Hudis, Clifford A. Isakoff, Steven J. Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Moran, Meena Patel, Sameer A. Pierce, Lori J. Reed, Elizabeth C. Salerno, Kilian E. Schwartzberg, Lee S. Smith, Karen Lisa Smith, Mary Lou Soliman, Hatem Somlo, George Telli, Melinda Ward, John H. Shead, Dorothy A. Kumar, Rashmi TI Breast Cancer Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID SKIN-SPARING MASTECTOMY; CONTRALATERAL PROPHYLACTIC MASTECTOMY; SENTINEL-NODE BIOPSY; RANDOMIZED CONTROLLED-TRIAL; POSTMASTECTOMY RADIATION IMPROVES; LUMPECTOMY PLUS TAMOXIFEN; OF-CLINICAL-ONCOLOGY; 20-YEAR FOLLOW-UP; CARCINOMA IN-SITU; AMERICAN-SOCIETY AB Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This portion of the NCCN Guidelines discusses recommendations specific to the locoregional management of clinical stage I, II, and IIIA (T3N1M0) tumors. C1 [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Anderson, Benjamin O.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Balassanian, Ron] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Blair, Sarah L.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Burstein, Harold J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cyr, Amy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Cyr, Amy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Elias, Anthony D.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Farrar, William B.] Solove Res Inst, Columbus, OH USA. [Forero, Andres] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Giordano, Sharon Hermes] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Goetz, Matthew] Mayo Clin, Ctr Canc, Rochester, MN USA. [Goldstein, Lori J.; Patel, Sameer A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Hudis, Clifford A.; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moran, Meena] Yale Canc Ctr, Smilow Canc Hosp, New Haven, CT USA. [Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Reed, Elizabeth C.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Salerno, Kilian E.] Roswell Pk Canc Inst, Buffalo, NY USA. [Schwartzberg, Lee S.] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Smith, Karen Lisa] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Smith, Mary Lou] Res Advocacy Network, Plano, TX USA. [Soliman, Hatem] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Telli, Melinda] Stanford Canc Inst, Stanford, CA USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Gradishar, WJ (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. NR 145 TC 40 Z9 46 U1 2 U2 11 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2015 VL 13 IS 4 BP 448 EP 475 PG 28 WC Oncology SC Oncology GA CG0NB UT WOS:000352962200010 PM 25870381 ER PT J AU Stricker, NH Keller, JE Castillo, DT Haaland, KY AF Stricker, Nikki H. Keller, Jenna E. Castillo, Diane T. Haaland, Kathleen Y. TI The Neurocognitive Performance of Female Veterans With Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID TRAUMATIC BRAIN-INJURY; INTIMATE PARTNER VIOLENCE; MEMORY MALINGERING TOMM; PSYCHOMETRIC PROPERTIES; VIETNAM VETERANS; PTSD; ATTENTION; DYSFUNCTION; DEFICITS; ABUSE AB Neurocognitive problems are common with posttraumatic stress disorder (PTSD) and are important to understand because of their association with the success of PTSD treatment and its potential neural correlates. To our knowledge, this is the first neurocognitive study in an all-female U.S. veteran sample, some of whom had PTSD. We examined neurocognitive performance and assessed whether learning deficits, common in PTSD, were associated with executive functioning. Veterans with PTSD (n = 56) and without (n = 53) were evaluated for psychiatric and neurocognitive status. The PTSD group had a lower estimated IQ (d = 0.53) and performed more poorly on all neurocognitive domains (d range = 0.57-0.88), except verbal retention (d = 0.04). A subset of the 2 groups that were matched on IQ and demographics similarly demonstrated poorer performance for the PTSD group on all neurocognitive domains (d range = 0.52-0.79), except verbal retention (d = 0.15). Within the PTSD group, executive functioning accounted for significant variance in verbal learning over and above IQ and processing speed (R-2 = .06), as well as depression (R-2 = .07) and PTSD severity (R-2 = .06). This study demonstrated that female veterans with PTSD performed more poorly than females without PTSD on several neurocognitive domains, including verbal learning, processing speed, and executive functioning. Replication of these results using a control group of veterans with more similar trauma exposure, history of mild traumatic brain injury, and psychiatric comorbidities would solidify these findings. Resumen Los problemas neurocognitivos son comunes en el trastorno por estres postraumatico (TEPT) y es importante entenderlos debido a su asociacion con el exito del tratamiento de TEPT y sus potenciales correlatos neurales. Hasta donde sabemos, es este el primer estudio neurocognitivo en una muestra solamente compuesta por mujeres veteranas, algunas de las cuales tenian TEPT. Examinamos el rendimiento neurocognitivo y evaluamos si los problemas de aprendizaje, comunes en TEPT, estaban asociados con el funcionamiento ejecutivo. Las veteranas con (56) y sin (53) TEPT fueron evaluadas en su estado psiquiatrico y neurocognitivo. El grupo TEPT tenia un CI estimado menor (d = 0.53) y rindieron mas pobremente en todos los dominios neurocognitivos (rango d = 0.57-0.88), excepto en la retencion verbal (d = 0.04). Un subconjunto de los 2 grupos, que tenian CI y datos demograficos comparables, demostraron rendimientos bajos similares en todos los dominios neurocognitivos (rango d = 0.52-0.79), excepto por la retencion verbal (d = 0.15). Dentro del grupo TEPT, el funcionamiento ejecutivo explica la varianza significativa en aprendizaje verbal por encima del CI y la velocidad de procesamiento (R2 = .06), como tambien la depresion (R2 = .07), y la gravedad del TEPT (R2 = .06). Este estudio demostro que las mujeres veteranas con TEPT rindieron peor que las mujeres sin TEPT en varios dominios neurocognitivos, incluyendo el aprendizaje verbal, la velocidad de procesamiento y el funcionamiento ejecutivo. La replicacion de estos resultados usando un grupo control de veteranos con exposicion similar al trauma, historia de leve LTC (lesion traumatica cerebral) y comorbilidades psiquiatricas podrian darle mayor solidez a estos hallazgos. Traditional and Simplified Chinese Abstracts by AsianSTSS ??: ?????????????????????? ??: ?????????????(PTSD)????????????PTSD?????????????????,??????????????????????,????????PTSD????????????????????????????????????PTSD?????????????????????PTSD?????(56)???PTSD?????(53)?????????????????PTSD??????IQ??? (d = 0.53),??????????????(d?? = 0.57-0.88),??????????(d = 0.04)? ?IQ???????????????,????????????????????(d?? = 0.52-0.79),??????????(d = 0.15)?PTSD??,????????IQ?????????????(R2 = .06)????(R2 = .07)?PTSD???(R2 = .06)???????????,??PTSD??????????PTSD???????????????????,????????????????????????????????????????????????????????????????,??????????? ??: ????????????????????? ??: ????????????(PTSD)???????????PTSD????????????????,?????????????????????,????????PTSD??????????????????????????????????PTSD?????????????????????PTSD?????(56)???PTSD?????(53)????????????????PTSD??????IQ??? (d = 0.53),??????????????(d?? = 0.57-0.88),??????????(d = 0.04)? ?IQ???????????????,???????????????????(d?? = 0.52-0.79),??????????(d = 0.15)?PTSD??,????????IQ?????????????(R2 = .06)????(R2 = .07)?PTSD???(R2 = .06)???????????,??PTSD??????????PTSD??????????????????,???????????????????????????????????????????????????????????????,??????????? C1 [Stricker, Nikki H.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Stricker, Nikki H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Keller, Jenna E.] Biomed Res Inst New Mexico, Albuquerque, NM USA. [Keller, Jenna E.; Castillo, Diane T.] New Mexico VA Healthcare Syst, Psychol Serv, Albuquerque, NM USA. [Castillo, Diane T.; Haaland, Kathleen Y.] New Mexico VA Healthcare Syst, Res Serv, Albuquerque, NM USA. [Castillo, Diane T.; Haaland, Kathleen Y.] Univ New Mexico, Sch Med, Dept Psychiat & Behav Sci, Albuquerque, NM 87131 USA. [Haaland, Kathleen Y.] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. RP Haaland, KY (reprint author), Univ New Mexico, Psychiat & Behav Sci, Sch Med, Family Practice & Psychiat & Behav Sci Bldg, Albuquerque, NM 87131 USA. EM khaaland@unm.edu FU Department of Defense [PT074309, W81XWH-08-2-0022]; Department of Veterans Affairs Research Career Scientist Award; Research Service at the NM-VAHCS; Department of Veterans Affairs VISN 1 Career Development Award-Mentored FX Portions of this manuscript were previously featured in a paper entitled "Neuropsychological Deficits in Female Veterans with PTSD: Preliminary Findings" presented at the 26 Annual Meeting of the International Society for Traumatic Stress Studies, Montreal, Quebec, Canada, November 4-6, 2010. This study was supported by the Department of Defense (Grant #PT074309, Award Number W81XWH-08-2-0022 to DC), Department of Veterans Affairs Research Career Scientist Award (KYH), a grant from the Research Service at the NM-VAHCS (KYH), and Department of Veterans Affairs VISN 1 Career Development Award-Mentored (NHS). NR 54 TC 3 Z9 3 U1 7 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2015 VL 28 IS 2 BP 102 EP 109 DI 10.1002/jts.22000 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CF8NJ UT WOS:000352818300003 PM 25847622 ER PT J AU Browne, KC Trim, RS Myers, US Norman, SB AF Browne, Kendall C. Trim, Ryan S. Myers, Ursula S. Norman, Sonya B. TI Trauma-Related Guilt: Conceptual Development and Relationship With Posttraumatic Stress and Depressive Symptoms SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID COGNITIVE-PROCESSING THERAPY; FEMALE RAPE VICTIMS; MULTIDIMENSIONAL MODEL; COMBAT VETERANS; PTSD; SHAME; DISORDER; EXPOSURE; SEVERITY; MILITARY AB Despite high prevalence and concerning associated problems, little effort has been made to conceptualize the construct of posttraumatic guilt. This investigation examined the theoretical model of trauma-related guilt proposed by Kubany and Watson (2003). This model hypothesizes that emotional and physical distress related to trauma memories partially mediates the relationship between guilt cognitions and posttraumatic guilt. Using path analysis, this investigation (a) empirically evaluated relationships hypothesized in Kubany and Watson's model, and (b) extended this conceptualization by evaluating models whereby guilt cognitions, distress, and posttraumatic guilt were related to posttraumatic stress disorder (PTSD) symptoms depression symptom severity. Participants were male U.S. Iraq and Afghanistan veterans (N=149). Results yielded a significant indirect effect from guilt cognitions to posttraumatic guilt via distress, providing support for Kubany and Watson's model ( = .14). Findings suggested distress may be the strongest correlate of PTSD symptoms (=.47) and depression symptoms (=.40), and that guilt cognitions may serve to intensify the relationship between distress and posttraumatic psychopathology. Research is needed to evaluate whether distress specific to guilt cognitions operates differentially on posttraumatic guilt when compared to distress more broadly related to trauma memories. Resumen A pesar de la alta prevalencia y los respectivos problemas asociados, se han realizado pocos esfuerzos para conceptualizar el constructo de culpa postraumatica. Esta investigacion examino el modelo teorico de culpa relacionada al trauma propuesto por Kubany y Warson (2003). Este modelo propone que el sufrimiento emocional y fisico relacionado a las memorias traumaticas media parcialmente la relacion entre las cogniciones de la culpa y la culpa postraumatica. Usando analisis de pautas, esta investigacion: (a) evaluo empiricamente las relaciones planteadas en el modelo de Kubany y Watson y (b) extendio esta conceptualizacion mediante la evaluacion de modelos en los cuales las cogniciones de la culpa, el sufrimiento y la culpa postraumatica estaban relacionadas al Trastorno por Estres Postraumatico (TEPT) y la severidad de los sintomas depresivos. Los participantes fueron hombres veteranos estadounidenses de Iraq y Afganistan (n = 149). Los resultados arrojaron un efecto indirecto significativo desde las cogniciones de la culpa hacia la culpa postraumatica via sufrimiento, apoyando el modelo de Kubany y Watson ( = .14). Los hallazgos sugieren que el sufrimiento puede ser el mas fuerte correlato del TEPT ( = .47) y los sintomas depresivos ( = .40) y que las cogniciones de la culpa pueden contribuir a intensificar la relacion entre el sufrimiento y la psicopatologia postraumatica. Se requiere investigacion para evaluar si el sufrimiento especifico a las cogniciones de la culpa opera diferencialmente en la culpa postraumatica cuando se le compara al sufrimiento relacionado en forma mas amplia a las memorias del trauma. Replicacion del Cuestionario de Historia de Incidente Critico: Frecuencia y Severidad de Exposicion a Trauma entre Oficiales de Agencias Policiales medianas y pequenas. Traditional and Simplified Chinese Abstracts by AsianSTSS ??: ???????????????????????????? ??: ?????????????,???????????,????????????????????????Kubany?Watson (2003)????????????????????????????????????,???????????????????????????????(?)?????Kubany?Watson????????;(?)??????,?????????????????????(PTSD)????????????????????????????????????(N = 149)????????,??????????????????????,?Kubany?Watson????????( =.14)???????,????PTSD ( = .47)?????( = .40) ???????,??????????????????????????????????????,??????????????,????????????????,???????????? ??: ???????????????????????????? ??: ?????????????,???????????,????????????????????????Kubany?Watson (2003)?????????????????????????????????????,???????????????????????????????(?)?????Kubany?Watson????????;(?)??????,?????????????????????(PTSD)????????????????????????????????????(N = 149)????????,??????????????????????,?Kubany?Watson????????( =.14)???????,????PTSD ( = .47)?????( = .40) ???????,??????????????????????????????????????,??????????????,????????????????,???????????? C1 [Browne, Kendall C.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Browne, Kendall C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Trim, Ryan S.] VA San Diego Healthcare Syst, San Diego, CA USA. [Trim, Ryan S.; Norman, Sonya B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Myers, Ursula S.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. [Norman, Sonya B.] Natl Ctr PTSD, White River Jct, VT USA. [Norman, Sonya B.] Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. RP Norman, SB (reprint author), VA San Diego, 3350 La Jolla Village Dr,MC116B, San Diego, CA 92161 USA. EM snorman@ucsd.edu FU NIAAA F31 award [5 F31 AA018909-02]; UCSD School of Medicine Faculty Research Award; VA Center of Excellence for Stress and Mental Health FX This material is the result of work supported by an NIAAA F31 award (5 F31 AA018909-02) to Dr. Kendall Browne, by a UCSD School of Medicine Faculty Research Award to Drs. Norman and Allard, by the VA Center of Excellence for Stress and Mental Health, and by resources from the U.S. Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, the VA Puget Sound Health Care System, Seattle, WA, and the VA San Diego Healthcare System, San Diego, CA. The views expressed in this article are those of the authors and do not represent the views of the Department of Veteran Affairs or the United States government. Authors would like to thank Dr. Sandra Brown, Dr. Joseph Price, Dr. Susan Tate, and Dr. V. Robin Weersing for their contributions to this work. NR 37 TC 3 Z9 3 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 2015 VL 28 IS 2 BP 134 EP 141 DI 10.1002/jts.21999 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CF8NJ UT WOS:000352818300007 PM 25864504 ER PT J AU Freitag, DF Butterworth, AS Willeit, P Howson, JMM Burgess, S Kaptoge, S Young, R Ho, WK Wood, AM Sweeting, M Spackman, S Staley, JR Ramond, A Harshfield, E Nielsen, SF Grande, P Lange, LA Bown, MJ Jones, GT Scott, RA Bevan, S Porcu, E Thorleifsson, G Zeng, LY Kessler, T Nikpay, M Do, R Zhang, WH Hopewell, JC Kleber, M Delgado, GE Nelson, CP Goel, A Bis, JC Dehghan, A Ligthart, S Smith, AV Qu, LM van 't Hof, FNG de Bakker, PIW Baas, AF van Rij, A Tromp, G Kuivaniemi, H Ritchie, MD Verma, SS Crawford, DC Malinowski, J de Andrade, M Kullo, IJ Peissig, PL McCarty, CA Bottinger, EP Gottesman, O Crosslin, DR Carrell, DS Rasmussen-Torvik, LJ Pacheco, JA Huang, J Timpson, NJ Kettunen, J Ala-Korpela, M Mitchell, GF Parsa, A Wilkinson, IB Gorski, M Li, Y Franceschini, N Keller, MF Ganesh, SK Langefeld, CD Bruijn, L Brown, MA Evans, DM Baltic, S Ferreira, MA Baurecht, H Weidinger, S Franke, A Lubitz, SA Muller-Nurasyid, M Felix, JF Smith, NL Sudman, M Thompson, SD Zeggini, E Panoutsopoulou, K Nalls, MA Singleton, A Polychronakos, C Bradfield, JP Hakonarson, H Easton, DF Thompson, D Tomlinson, IP Dunlop, M Hemminki, K Morgan, G Eisen, T Goldschmidt, H Allan, JM Henrion, M Whiffin, N Wang, YF Chubb, D Houlston, RS Iles, MM Bishop, DT Law, MH Hayward, NK Luo, Y Nejentsev, S Barbalic, M Crossman, D Sanna, S Soranzo, N Markus, HS Wareham, NJ Rader, DJ Reilly, M Assimes, T Harris, TB Hofman, A Franco, OH Gudnason, V Tracy, R Psaty, BM Farrall, M Watkins, H Hall, AS Samani, NJ Marz, W Clarke, R Collins, R Kooner, JS Chambers, JC Kathiresan, S McPherson, R Erdmann, J Kastrati, A Schunkert, H Stefansson, K Thorsteinsdottir, U Walston, JD Tybjaerg-Hansen, A Alam, DS Majumder, AA Di Angelantonio, E Chowdhury, R Nordestgaard, BG Saleheen, D Thompson, SG Danesh, J AF Freitag, Daniel F. Butterworth, Adam S. Willeit, Peter Howson, Joanna M. M. Burgess, Stephen Kaptoge, Stephen Young, Robin Ho, Weang Kee Wood, Angela M. Sweeting, Michael Spackman, Sarah Staley, James R. Ramond, Anna Harshfield, Eric Nielsen, Sune F. Grande, Peer Lange, Leslie A. Bown, Matthew J. Jones, Gregory T. Scott, Robert A. Bevan, Steve Porcu, Eleonora Thorleifsson, Gudmar Zeng, Lingyao Kessler, Thorsten Nikpay, Majid Do, Ron Zhang, Weihua Hopewell, Jemma C. Kleber, Marcus Delgado, Graciela E. Nelson, Christopher P. Goel, Anuj Bis, Joshua C. Dehghan, Abbas Ligthart, Symen Smith, Albert V. Qu, Liming van 't Hof, Femke N. G. de Bakker, Paul I. W. Baas, Annette F. van Rij, Andre Tromp, Gerard Kuivaniemi, Helena Ritchie, Marylyn D. Verma, Shefali S. Crawford, Dana C. Malinowski, Jennifer de Andrade, Mariza Kullo, Iftikhar J. Peissig, Peggy L. McCarty, Catherine A. Boettinger, Erwin P. Gottesman, Omri Crosslin, David R. Carrell, David S. Rasmussen-Torvik, Laura J. Pacheco, Jennifer A. Huang, Jie Timpson, Nicholas J. Kettunen, Johannes Ala-Korpela, Mika Mitchell, Gary F. Parsa, Afshin Wilkinson, Ian B. Gorski, Mathias Li, Yong Franceschini, Nora Keller, Margaux F. Ganesh, Santhi K. Langefeld, Carl D. Bruijn, Lucie Brown, Matthew A. Evans, David M. Baltic, Svetlana Ferreira, Manuel A. Baurecht, Hansjoerg Weidinger, Stephan Franke, Andre Lubitz, Steven A. Mueller-Nurasyid, Martina Felix, Janine F. Smith, Nicholas L. Sudman, Marc Thompson, Susan D. Zeggini, Eleftheria Panoutsopoulou, Kalliope Nalls, Mike A. Singleton, Andrew Polychronakos, Constantin Bradfield, Jonathan P. Hakonarson, Hakon Easton, Douglas F. Thompson, Deborah Tomlinson, Ian P. Dunlop, Malcolm Hemminki, Kari Morgan, Gareth Eisen, Timothy Goldschmidt, Hartmut Allan, James M. Henrion, Marc Whiffin, Nicola Wang, Yufei Chubb, Daniel Houlston, Richard S. Iles, Mark M. Bishop, D. Timothy Law, Matthew H. Hayward, Nicholas K. Luo, Yang Nejentsev, Sergey Barbalic, Maja Crossman, David Sanna, Serena Soranzo, Nicole Markus, Hugh S. Wareham, Nicholas J. Rader, Daniel J. Reilly, Muredach Assimes, Themistocles Harris, Tamara B. Hofman, Albert Franco, Oscar H. Gudnason, Vilmundur Tracy, Russell Psaty, Bruce M. Farrall, Martin Watkins, Hugh Hall, Alistair S. Samani, Nilesh J. Maerz, Winfried Clarke, Robert Collins, Rory Kooner, Jaspal S. Chambers, John C. Kathiresan, Sekar McPherson, Ruth Erdmann, Jeanette Kastrati, Adnan Schunkert, Heribert Stefansson, Kari Thorsteinsdottir, Unnur Walston, Jeremy D. Tybjaerg-Hansen, Anne Alam, Dewan S. Majumder, Abdullah Al Shafi Di Angelantonio, Emanuele Chowdhury, Rajiv Nordestgaard, Borge G. Saleheen, Danish Thompson, Simon G. Danesh, John CA Interleukin 1 Genetics Consortium European Prospective Invest Canc Aneurysm Consortium Elect Med Records & Genomics Netwo UK 10K Consortium European Prospective Invest Canc METASTROKE Consortium Chronic Kidney Dis Genetics Consor Cohorts Heart & Aging Res Genomic Australo-Anglo-Amer Spondyloarthri Australian Asthma Genetics Consort Atrial Fribrillation Genetics Cons Cohorts Heart & Aging Res Genomic Consortium Juvenile Arthritis Gene Arthritis Res UK Osteoarthritis Ge Int Parkinson's Dis Consortium Breast Canc Assoc Consortium Melanoma Genetics Consortium Cohorts Heart & Aging Res Genomic Myocardial Infarction Genetics Con TI Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; SUSCEPTIBILITY LOCUS; SEQUENCE VARIANT; COMMON VARIANTS; HEART-DISEASE; DOUBLE-BLIND AB Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND. C1 [Freitag, Daniel F.; Butterworth, Adam S.; Willeit, Peter; Howson, Joanna M. M.; Burgess, Stephen; Kaptoge, Stephen; Young, Robin; Ho, Weang Kee; Wood, Angela M.; Sweeting, Michael; Spackman, Sarah; Staley, James R.; Ramond, Anna; Harshfield, Eric; Bevan, Steve; Wilkinson, Ian B.; Easton, Douglas F.; Thompson, Deborah; Nejentsev, Sergey; Markus, Hugh S.; Di Angelantonio, Emanuele; Chowdhury, Rajiv; Saleheen, Danish; Thompson, Simon G.; Danesh, John] Univ Cambridge, Cambridge CB1 8RN, England. [Nielsen, Sune F.; Grande, Peer; Tybjaerg-Hansen, Anne; Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Univ Hosp, Copenhagen, Denmark. [Lange, Leslie A.; Franceschini, Nora] Univ N Carolina, Chapel Hill, NC USA. [Nelson, Christopher P.; Brown, Matthew A.; Samani, Nilesh J.] Univ Leicester, Leicester, Leics, England. [Nelson, Christopher P.; Brown, Matthew A.; Samani, Nilesh J.] Leicester Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester, Leics, England. [Jones, Gregory T.; van Rij, Andre] Univ Otago, Dunedin, New Zealand. [Scott, Robert A.; Wareham, Nicholas J.] MRC, Epidemiol Unit, Cambridge, England. [Porcu, Eleonora; Sanna, Serena] Ist Ric Genet & Biomed, Monserrato, Italy. [Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet Amgen, Reykjavik, Iceland. [Zeng, Lingyao; Kessler, Thorsten; Kastrati, Adnan; Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Zeng, Lingyao; Kessler, Thorsten; Mueller-Nurasyid, Martina; Kastrati, Adnan; Schunkert, Heribert] German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany. [Nikpay, Majid; McPherson, Ruth] Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada. [Do, Ron; Kathiresan, Sekar] Broad Inst, Cambridge, England. [Do, Ron; Lubitz, Steven A.; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhang, Weihua; Kooner, Jaspal S.; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, London, England. [Hopewell, Jemma C.; Goel, Anuj; Farrall, Martin; Clarke, Robert; Collins, Rory] Univ Oxford, Oxford, England. [Kleber, Marcus; Delgado, Graciela E.; Goldschmidt, Hartmut] Heidelberg Univ, Heidelberg, Germany. [Bis, Joshua C.; Crosslin, David R.; Smith, Nicholas L.; Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Dehghan, Abbas; Ligthart, Symen; Felix, Janine F.; Hofman, Albert; Franco, Oscar H.] Univ Med Ctr Rotterdam, Erasmus Med Ctr, Rotterdam, Netherlands. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Reykjavik, Iceland. [Qu, Liming; Saleheen, Danish] Univ Penn, Philadelphia, PA 19104 USA. [van 't Hof, Femke N. G.; de Bakker, Paul I. W.; Baas, Annette F.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Tromp, Gerard; Kuivaniemi, Helena] Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA. [Ritchie, Marylyn D.; Verma, Shefali S.] Penn State Univ, University Pk, PA 16802 USA. [Crawford, Dana C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Malinowski, Jennifer] Yale Univ, New Haven, CT USA. [de Andrade, Mariza; Kullo, Iftikhar J.] Mayo Clin, Rochester, MN USA. [Peissig, Peggy L.] Marshfield Clin Res Fdn, Marshfield, WI USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Div Res, Duluth, MN USA. [Boettinger, Erwin P.; Gottesman, Omri] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Carrell, David S.] Grp Hlth Res Inst, Seattle, WA USA. [Rasmussen-Torvik, Laura J.; Pacheco, Jennifer A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Huang, Jie; Zeggini, Eleftheria; Panoutsopoulou, Kalliope; Luo, Yang; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge, England. [Timpson, Nicholas J.] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England. [Kettunen, Johannes; Ala-Korpela, Mika] Univ Oulu, Oulu, Finland. [Kettunen, Johannes] Natl Inst Hlth & Welf, Helsinki, Finland. [Ala-Korpela, Mika] Univ Bristol, Bristol, Avon, England. [Parsa, Afshin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Gorski, Mathias] Univ Regensburg, D-93053 Regensburg, Germany. [Li, Yong] Univ Hosp Freiburg, Freiburg, Germany. [Keller, Margaux F.; Nalls, Mike A.; Singleton, Andrew] NIA, NIH, Bethesda, MD 20892 USA. [Ganesh, Santhi K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA. [Bruijn, Lucie] Amyotroph Lateral Sclerosis Assoc, Washington, DC USA. [Brown, Matthew A.; Evans, David M.] Univ Queensland, Princess Alexandra Hosp, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia. [Baltic, Svetlana] Univ Western Australia, Perth, WA 6009, Australia. [Ferreira, Manuel A.; Law, Matthew H.; Hayward, Nicholas K.] Queensland Inst Med Res, Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Baurecht, Hansjoerg; Weidinger, Stephan] Univ Hosp Schleswig Holstein, Kiel, Germany. [Franke, Andre] Univ Kiel, Kiel, Germany. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, D-81377 Munich, Germany. [Sudman, Marc; Thompson, Susan D.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Polychronakos, Constantin] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Bradfield, Jonathan P.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Tomlinson, Ian P.] Wellcome Trust Ctr Human Genet, Oxford, England. [Dunlop, Malcolm] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Dunlop, Malcolm] MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. [Hemminki, Kari] German Canc Res Ctr, Heidelberg, Germany. [Hemminki, Kari] Lund Univ, Malmo, Sweden. [Morgan, Gareth] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Eisen, Timothy] Cambridge Univ Hlth Partners, Cambridge, England. [Goldschmidt, Hartmut] Natl Ctr Tumor Dis, Heidelberg, Germany. [Allan, James M.] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Henrion, Marc; Whiffin, Nicola; Wang, Yufei; Chubb, Daniel] Inst Canc Res, Sutton, Surrey, England. [Houlston, Richard S.] Inst Canc Res, London SW3 6JB, England. [Iles, Mark M.; Bishop, D. Timothy] Univ Leeds, Leeds Canc Res UK Ctr, Leeds, W Yorkshire, England. [Barbalic, Maja] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Crossman, David] Univ St Andrews, St Andrews, Fife, Scotland. [Rader, Daniel J.; Reilly, Muredach] Univ Penn, Perleman Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA USA. [Rader, Daniel J.; Reilly, Muredach] Univ Penn, Perleman Sch Med, Cardiovasc Inst, Philadelphia, PA USA. [Assimes, Themistocles] Stanford Univ, Stanford, CA 94305 USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Tracy, Russell] Univ Vermont, Coll Med, Burlington, VT USA. [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, Mannheim, Germany. [Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany. [Erdmann, Jeanette] German Res Ctr Cardiovasc Res, Lubeck, Germany. [Walston, Jeremy D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Alam, Dewan S.] Int Ctr Diarrhoeal Dis Res, Ctr Control Chron Dis, Dhaka 1000, Bangladesh. [Majumder, Abdullah Al Shafi] Natl Inst Cardiovasc Dis, Dhaka, Bangladesh. RP Freitag, DF (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Interleukin Genet Consortium Coordinating Ctr 1, Cambridge CB1 8RN, England. EM IL1GC@medschl.cam.ac.uk RI Erdmann, Jeanette/P-7513-2014; de Bakker, Paul/B-8730-2009; Gudnason, Vilmundur/K-6885-2015; Singleton, Andrew/C-3010-2009; Kessler, Thorsten/O-7426-2015; Smith, Albert/K-5150-2015; Bown, Matthew/P-1957-2016; Dunlop, Malcolm/F-1973-2011; Weidinger, Stephan/C-8461-2011; OI Jones, Gregory T/0000-0002-6950-4210; Evans, David/0000-0003-0663-4621; Burgess, Stephen/0000-0001-5365-8760; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Houlston, Richard/0000-0002-5268-0242; Ramond, Anna/0000-0002-9958-3693; Di Angelantonio, Emanuele/0000-0001-8776-6719; Willeit, Peter/0000-0002-1866-7159; Baltic, Svetlana/0000-0002-3428-940X; HO, WEANG KEE/0000-0002-8269-7344; Kuivaniemi, Helena/0000-0001-5753-8766; Erdmann, Jeanette/0000-0002-4486-6231; Zeggini, Eleftheria/0000-0003-4238-659X; Bevan, Steve/0000-0003-0490-6830; Bishop, Tim/0000-0002-8752-8785; Felix, Janine/0000-0002-9801-5774; de Bakker, Paul/0000-0001-7735-7858; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Bown, Matthew/0000-0002-6180-3611; Dunlop, Malcolm/0000-0002-3033-5851; Luo, Yang/0000-0001-7385-6166 FU UK Medical Research Council; British Heart Foundation; UK National Institute for Health Research; National Institute for Health Research Cambridge Biomedical Research Centre; European Research Council; European Commission FX UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7. NR 56 TC 20 Z9 20 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD APR PY 2015 VL 3 IS 4 BP 243 EP 253 DI 10.1016/S2213-8587(15)00034-0 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG1KX UT WOS:000353032600020 ER PT J AU Doshi, BN Ghali, B Godleski-Beckos, C Lozynsky, AJ Oral, E Muratoglu, OK AF Doshi, Brinda N. Ghali, Bassem Godleski-Beckos, Christine Lozynsky, Andrew J. Oral, Ebru Muratoglu, Orhun K. TI High Pressure Crystallization of Vitamin E-Containing Radiation Cross-linked UHMWPE SO MACROMOLECULAR MATERIALS AND ENGINEERING LA English DT Article DE cross-linking; fatigue; joint arthroplasty; polyethylene; vitamin E ID MOLECULAR-WEIGHT POLYETHYLENE; FATIGUE RESISTANCE; ALPHA-TOCOPHEROL; LOW WEAR; TEMPERATURE; IRRADIATION; OXIDATION AB One of our aims in developing ultrahigh molecular weight polyethylene (UHMWPE) joint implants is to improve the fatigue strength of cross-linked UHMWPEs without sacrificing their wear resistance induced by cross-linking. High pressure crystallization (HPC) of uncross-linked UHMWPE, which results in the formation of less hindered extended chain crystals, increased fatigue strength. Vitamin E, also an antioxidant, acted synergistically with HPC and the resulting UHMWPE had increased wear and fatigue strength. In this study, we hypothesized that vitamin E-blended, cross-linked, and high pressure crystallized UHMWPE (X-VEHPE) would have higher wear resistance and fatigue strength compared to radiation cross-linked UHMWPE. To test this hypothesis, we irradiated 0.1 wt% vitamin E-blended UHMWPE, subsequently radiation cross-linked it to various doses and terminally high pressure crystallized it. We used bi-directional pin-on-disc wear testing, tensile mechanical testing, and fatigue crack propagation resistance testing. We found that X-VEHPE required less radiation dose and less cross-linking to achieve the same wear rate when compared to irradiated UHMWPE and had improved fatigue resistance at the same wear rate. Therefore, this UHMWPE presented about 46 and 87% improvement in fatigue strength compared to irradiated and irradiated/melted UHMWPE and may be a feasible alternative for joint implants. C1 [Doshi, Brinda N.; Ghali, Bassem; Godleski-Beckos, Christine; Lozynsky, Andrew J.; Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St GRJ 1206, Boston, MA 02114 USA. EM eoral@partners.org FU NIH [AR051142] FX This study was funded by NIH Grant No. AR051142 and departmental funds. NR 24 TC 1 Z9 1 U1 2 U2 23 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1438-7492 EI 1439-2054 J9 MACROMOL MATER ENG JI Macromol. Mater. Eng. PD APR PY 2015 VL 300 IS 4 BP 458 EP 465 DI 10.1002/mame.201400294 PG 8 WC Materials Science, Multidisciplinary; Polymer Science SC Materials Science; Polymer Science GA CF6DD UT WOS:000352646000008 ER PT J AU Doolan, PJ Royle, G Gibson, A Lu, HM Prieels, D Bentefour, EH AF Doolan, P. J. Royle, G. Gibson, A. Lu, H. -M. Prieels, D. Bentefour, E. H. TI Dose ratio proton radiography using the proximal side of the Bragg peak SO MEDICAL PHYSICS LA English DT Article DE single-detector proton radiography; proton therapy; WEPL; WET; dose ratio method ID VIVO RANGE VERIFICATION; ACTIVE PIXEL SENSOR; HEAVY-ION CT; COMPUTED-TOMOGRAPHY; STOPPING POWER; SPATIAL-RESOLUTION; CONCEPTUAL DESIGN; DETECTOR SYSTEM; MONTE-CARLO; THERAPY AB Purpose: In recent years, there has been a movement toward single-detector proton radiography, due to its potential ease of implementation within the clinical environment. One such single-detector technique is the dose ratio method in which the dose maps from two pristine Bragg peaks are recorded beyond the patient. To date, this has only been investigated on the distal side of the lower energy Bragg peak, due to the sharp falloff. The authors investigate the limits and applicability of the dose ratio method on the proximal side of the lower energy Bragg peak, which has the potential to allow a much wider range of water-equivalent thicknesses (WET) to be imaged. Comparisons are made with the use of the distal side of the Bragg peak. Methods: Using the analytical approximation for the Bragg peak, the authors generated theoretical dose ratio curves for a range of energy pairs, and then determined how an uncertainty in the dose ratio would translate to a spread in the WET estimate. By defining this spread as the accuracy one could achieve in the WET estimate, the authors were able to generate lookup graphs of the range on the proximal side of the Bragg peak that one could reliably use. These were dependent on the energy pair, noise level in the dose ratio image and the required accuracy in the WET. Using these lookup graphs, the authors investigated the applicability of the technique for a range of patient treatment sites. The authors validated the theoretical approach with experimental measurements using a complementary metal oxide semiconductor active pixel sensor (CMOS APS), by imaging a small sapphire sphere in a high energy proton beam. Results: Provided the noise level in the dose ratio image was 1% or less, a larger spread of WETs could be imaged using the proximal side of the Bragg peak (max 5.31 cm) compared to the distal side (max 2.42 cm). In simulation, it was found that, for a pediatric brain, it is possible to use the technique to image a region with a square field equivalent size of 7.6 cm(2), for a required accuracy in the WET of 3 mm and a 1% noise level in the dose ratio image. The technique showed limited applicability for other patient sites. The CMOS APS demonstrated a good accuracy, with a root-mean-square-error of 1.6 mm WET. The noise in the measured images was found to be sigma = 1.2% (standard deviation) and theoretical predictions with a 1.96 sigma noise level showed good agreement with the measured errors. Conclusions: After validating the theoretical approach with measurements, the authors have shown that the use of the proximal side of the Bragg peak when performing dose ratio imaging is feasible, and allows for a wider dynamic range than when using the distal side. The dynamic range available increases as the demand on the accuracy of the WET decreases. The technique can only be applied to clinical sites with small maximum WETs such as for pediatric brains. (C) 2015 Author(s). C1 [Doolan, P. J.; Royle, G.; Gibson, A.] UCL, Dept Med Phys & Bioengn, London WC1E 6BT, England. [Lu, H. -M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Prieels, D.; Bentefour, E. H.] IBA, B-1348 Louvain La Neuve, Belgium. RP Doolan, PJ (reprint author), UCL, Dept Med Phys & Bioengn, London WC1E 6BT, England. EM paul.doolan.09@ucl.ac.uk FU Engineering and Physical Sciences Research Council (UK); Ion Beam Applications (Louvain-La-Neuve, Belgium) FX The authors would like to acknowledge the support of the operators at Massachusetts General Hospital. This project was funded equally by the Engineering and Physical Sciences Research Council (UK) and Ion Beam Applications (Louvain-La-Neuve, Belgium). NR 52 TC 2 Z9 2 U1 1 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2015 VL 42 IS 4 BP 1871 EP 1883 DI 10.1118/1.4915492 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF0ZL UT WOS:000352273200041 PM 25832077 ER PT J AU Bentefour, EH Tang, SK Cascio, EW Testa, M Samuel, D Prieels, D Gottschalk, B Lu, HM AF Bentefour, El H. Tang, Shikui Cascio, Ethan W. Testa, Mauro Samuel, Deepak Prieels, Damien Gottschalk, Bernard Lu, Hsiao-Ming TI Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements SO MEDICAL PHYSICS LA English DT Article DE proton therapy; in-vivo range verification; diode dosimeter; prostate AP field ID DIODE DOSIMETRY; STOPPING-POWER; THERAPY; VERIFICATION; UNCERTAINTIES; RADIATION; PATIENT AB Purpose: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. Methods: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3x4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. Results: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with +/- 1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. Conclusions: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments. (C) 2015 American Association of Physicists in Medicine. C1 [Bentefour, El H.; Prieels, Damien] IBA, B-1348 Louvain La Neuve, Belgium. [Tang, Shikui; Cascio, Ethan W.; Testa, Mauro; Lu, Hsiao-Ming] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Samuel, Deepak] Catholic Univ Louvain, ICTEAM Inst, B-1348 Louvain La Neuve, Belgium. [Gottschalk, Bernard] Harvard Univ, Lab Particle Phys & Cosmol, Cambridge, MA 01238 USA. RP Bentefour, EH (reprint author), IBA, 3 Chemin Cyclotron, B-1348 Louvain La Neuve, Belgium. EM hassan.bentefour@iba-group.com RI Samuel, Deepak/B-6482-2017 OI Samuel, Deepak/0000-0002-4560-5957 FU Region Walloon - Belgium [IMAGX/PPP-1]; MGH-NIH Federal Share Grant; NIH/NCI [p01 CA21239]; Harvard University Physics Department FX This work was partly funded by IMAGX/PPP-1 of Region Walloon - Belgium and was supported in part by MGH-NIH Federal Share Grant and NIH/NCI p01 CA21239. One of the authors, Bernard Gottschalk thanks the Harvard University Physics Department for ongoing support. NR 22 TC 6 Z9 6 U1 1 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2015 VL 42 IS 4 BP 1936 EP 1947 DI 10.1118/1.4915923 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF0ZL UT WOS:000352273200048 ER PT J AU Hixson, JD Van Bebber, SL Bertko, KM AF Hixson, John D. Van Bebber, Stephanie L. Bertko, Kate M. TI Interest in a Digital Health Tool in Veterans With Epilepsy: Results of a Phone Survey SO MILITARY MEDICINE LA English DT Article ID SELF-MANAGEMENT; CHRONIC DISEASE; INTERNET; ADULTS; INFORMATION; PROGRAM; ONLINE; TRIAL AB Objective: Online tools for managing chronic health conditions are becoming increasingly popular. Perceived benefits include ease of use, low costs, and availability but are contingent on patient engagement, Internet access, and digital literacy. This article describes data collected during the recruitment phase of a study evaluating an online self- management platform for epilepsy in a U.S. Veteran population. Methods: We used administrative data to identify and contact Veterans with a likely diagnosis of epilepsy in the Veterans Health Administration (VHA). Veterans who did not respond directly to a mailed invitation were recruited by phone to determine study interest and evaluate digital access. Results: Of the 2,143 Veterans mailed study invitations, phone calls were made to 1,789 who did not specifically decline participation. Among those reached by phone (n = 1,053): 295 (28%) expressed interest in the study and an online tool, 333 (19%) reported a lack of computer and/or Internet access and 425 (40%) were not interested for other reasons. Conclusions: This study suggests an interest in online tools for managing health despite the fact that some Veterans lack computer and/or Internet access. As investment in digital health solutions grows, the VHA should prioritize the widespread provision of digital access to more Veterans. C1 [Hixson, John D.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94122 USA. [Hixson, John D.; Van Bebber, Stephanie L.; Bertko, Kate M.] San Francisco VA Med Ctr, Epilepsy Ctr Excellence, San Francisco, CA 94121 USA. [Hixson, John D.; Van Bebber, Stephanie L.; Bertko, Kate M.] Northern Calif Inst Res & Educ, San Francisco, CA 94121 USA. RP Hixson, JD (reprint author), Univ Calif San Francisco, Dept Neurol, 400 Parnassus Ave, San Francisco, CA 94122 USA. FU Epilepsy Centers for Excellence (ECoE) Network; San Francisco Veterans Affairs Medical Center FX We acknowledge the support of Dr. Karen Parko and John Haupert in conducting this study. This material is the result of work supported with resources and the use of facilities of the Epilepsy Centers for Excellence (ECoE) Network and the San Francisco Veterans Affairs Medical Center. This study was an industry-sponsored, investigator-initiated trial. NR 19 TC 3 Z9 3 U1 1 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD APR PY 2015 VL 180 IS 4 BP 387 EP 390 DI 10.7205/MILMED-D-14-00224 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CF6UJ UT WOS:000352691600005 PM 25826343 ER PT J AU Vanderver, A Prust, M Tonduti, D Mochel, F Hussey, HM Helman, G Garbern, J Eichler, F Labauge, P Aubourg, P Rodriguez, D Patterson, MC Van Hove, JLK Schmidt, J Wolf, NI Boespflug-Tanguy, O Schiffmann, R van der Knaap, MS AF Vanderver, Adeline Prust, Morgan Tonduti, Davide Mochel, Fanny Hussey, Heather M. Helman, Guy Garbern, James Eichler, Florian Labauge, Pierre Aubourg, Patrick Rodriguez, Diana Patterson, Marc C. Van Hove, Johan L. K. Schmidt, Johanna Wolf, Nicole I. Boespflug-Tanguy, Odile Schiffmann, Raphael van der Knaap, Marjo S. CA GLIA Consortium TI Case definition and classification of leukodystrophies and leukoencephalopathies SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Leukodystrophy; Glia; Myelin; Genetic leukoencephalopathy ID HYPOMYELINATION; MUTATIONS; ALPHA AB Objective: An approved definition of the term leukodystrophy does not currently exist. The lack of a precise case definition hampers efforts to study the epidemiology and the relevance of genetic white matter disorders to public health. Method: Thirteen experts at multiple institutions participated in iterative consensus building surveys to achieve definition and classification of disorders as leukodystrophies using a modified Delphi approach. Results: A case definition for the leukodystrophies was achieved, and a total of 30 disorders were classified under this definition. In addition, a separate set of disorders with heritable white matter abnormalities but not meeting criteria for leukodystrophy, due to presumed primary neuronal involvement and prominent systemic manifestations, was classified as genetic leukoencephalopathies (gLE). Interpretation: A case definition of leukodystrophies and classification of heritable white matter disorders will permit more detailed epidemiologic studies of these disorders. (C) 2015 Elsevier Inc. All rights reserved. C1 [Vanderver, Adeline; Prust, Morgan; Helman, Guy; Schmidt, Johanna] Childrens Natl Hlth Syst, Dept Neurol, Washington, DC 20010 USA. [Vanderver, Adeline; Prust, Morgan; Helman, Guy; Schmidt, Johanna] Childrens Natl Hlth Syst, Med Genet Res Ctr, Washington, DC 20010 USA. [Vanderver, Adeline] George Washington Univ, Sch Med, Dept Integrated Syst Biol, Washington, DC USA. [Tonduti, Davide] Univ Pavia, Dept Brain & Behav Sci, Child Neuropsychiat Unit, I-27100 Pavia, Italy. [Tonduti, Davide] Fdn IRCCS Ist Neurol Carlo Besta, Dept Child Neurol, Milan, Italy. [Mochel, Fanny] Univ Paris 06, Sorbonne Univ, Inst Cerveau & Moelle Epiniere, INSERM U1127,CNRS UMR 7225,UMR S 1127, Paris, France. [Mochel, Fanny] Grp Hosp Pitie Salpetriere, AP HP, Dept Genet, F-75634 Paris, France. [Hussey, Heather M.] George Washington Univ, Milken Inst Sch Publ Hlth, Washington, DC USA. [Garbern, James] Univ Rochester, Rochester, NY USA. [Eichler, Florian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Labauge, Pierre] CHU Montpellier, Dept Neurol, Montpellier, France. [Aubourg, Patrick] Hop Bicetre, Dept Pediat Neurol, Inserm U986, F-94275 Le Kremlin Bicetre, France. [Rodriguez, Diana] Univ Paris 06, Hop Armand Trousseau, AP HP, Serv Neuropediat,Insenn U676, Paris, France. [Patterson, Marc C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Patterson, Marc C.] Mayo Clin, Dept Pediat, Rochester, MN USA. [Patterson, Marc C.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Van Hove, Johan L. K.] Univ Colorado, Dept Pediat, Genet Sect, Aurora, CO USA. [Wolf, Nicole I.; van der Knaap, Marjo S.] Vrije Univ Amsterdam Med Ctr, Dept Child Neurol, Amsterdam, Netherlands. [Wolf, Nicole I.; van der Knaap, Marjo S.] Neurosci Campus, Amsterdam, Netherlands. [Boespflug-Tanguy, Odile] Hop Robert Debre, French Reference Ctr Leukodystrophies, Dept Pediat Neurol & Metab Disorders, F-75019 Paris, France. [Boespflug-Tanguy, Odile] Paris Diderot Univ, Sorbonne Paris Cite, Inserm Neuroprotect UMR1141, Paris, France. [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. RP Vanderver, A (reprint author), Childrens Natl Hlth Syst, 111 Michigan Ave, Washington, DC 20010 USA. EM avanderv@childrensnational.org RI tonduti, davide/K-1673-2016; Helman, Guy/C-7935-2017; OI tonduti, davide/0000-0001-9371-7454; Helman, Guy/0000-0002-4784-7423; Patterson, Marc/0000-0002-1116-126X FU National Institutes of Health, NINDS [1K08N5060695, U54NS065768-02]; Myelin Disorders Bioregistry Project; Actelion; National MS Society; Actelion Pharmaceuticals: Research grants FX AV: Supported by grants from the National Institutes of Health, NINDS (1K08N5060695) and the Myelin Disorders Bioregistry Project. MCP: Funding: Actelion, National Institutes of Health, NINDS (U54NS065768-02), National MS Society. Actelion Pharmaceuticals: Research grants; travel expenses; consulting honoraria directed to Mayo Clinic; Genzyme (Sanofi): Consulting; Amicus: Data Safety Monitoring Board; Orphazyme (Denmark): Consulting; consulting honoraria directed to Mayo Clinic; Shire Human Genetic Therapies: travel expenses; consulting honoraria directed to Mayo Clinic; Stem Cells, Inc.: Chair, Data Monitoring Committee; honorarium retained; Up-To-Date: Section Editor; royalties retained; Journal of Child Neurology: Editorial Board (no compensation); WHO International Advisory Group on revision of ICD-10: ICNA representative (no compensation); IOM Committee to Review Adverse Effects of Vaccines: member (no compensation) completed. NR 13 TC 24 Z9 25 U1 4 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2015 VL 114 IS 4 BP 494 EP 500 DI 10.1016/j.ymgme.2015.01.006 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CG1BV UT WOS:000353008900002 PM 25649058 ER PT J AU Helman, G Van Haren, K Bonkowsky, JL Bernard, G Pizzino, A Braverman, N Suhr, D Patterson, MC Fatemi, SA Leonard, J van der Knaap, MS Back, SA Damiani, S Goldman, SA Takanohashi, A Petryniak, M Rowitch, D Messing, A Wrabetz, L Schiffmann, R Eichler, F Escolar, ML Vanderver, A AF Helman, Guy Van Haren, Keith Bonkowsky, Joshua L. Bernard, Genevieve Pizzino, Amy Braverman, Nancy Suhr, Dean Patterson, Marc C. Fatemi, S. Ali Leonard, Jeff van der Knaap, Marjo S. Back, Stephen A. Damiani, Stephen Goldman, Steven A. Takanohashi, Asako Petryniak, Magdalena Rowitch, David Messing, Albee Wrabetz, Lawrence Schiffmann, Raphael Eichler, Florian Escolar, Maria L. Vanderver, Adeline CA GLIA Consortium TI Disease specific therapies in leukodystrophies and leukoencephalopathies SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Leukodystrophy; Consensus; Therapy; Care; Outcomes; Prevention ID X-LINKED ADRENOLEUKODYSTROPHY; AICARDI-GOUTIERES-SYNDROME; UMBILICAL-CORD BLOOD; BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; INFANTILE KRABBE-DISEASE; CHAIN FATTY-ACID; METACHROMATIC LEUKODYSTROPHY; CEREBROTENDINOUS XANTHOMATOSIS; PHARMACOLOGICAL CHAPERONES AB Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms associated with leukodystrophies has allowed clinicians and researchers to prioritize treatment strategies and advance research in therapies for specific disorders, some of which are on the verge of pilot or Phase I/II clinical trials. This shifts the care of leukodystrophy patients from the management of the complex array of symptoms and sequelae alone to targeted therapeutics. The unmet needs of leukodystrophy patients still remain an overwhelming burden. While the overwhelming consensus is that these disorders collectively are symptomatically treatable, leukodystrophy patients are in need of advanced therapies and if possible, a cure. (C) 2015 Elsevier Inc. All rights reserved. C1 [Helman, Guy; Vanderver, Adeline] Childrens Natl Hlth Syst, Dept Neurol, Washington, DC 20001 USA. [Van Haren, Keith; Pizzino, Amy] Lucile Packard Childrens Hosp, Dept Neurol, Stanford, CA USA. [Van Haren, Keith; Pizzino, Amy] Stanford Univ, Sch Med, Stanford, CA USA. [Bonkowsky, Joshua L.] Univ Utah, Sch Med, Dept Pediat & Neurol, Salt Lake City, UT USA. [Bernard, Genevieve] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat, Montreal, PQ H3H 1P3, Canada. [Bernard, Genevieve] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Neurol & Neurosurg, Montreal, PQ H3H 1P3, Canada. [Braverman, Nancy] McGill Univ, Dept Human Genet & Pediat, Montreal, PQ, Canada. [Braverman, Nancy] Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada. [Patterson, Marc C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Patterson, Marc C.] Mayo Clin, Dept Pediat & Med Genet, Rochester, MN USA. [Fatemi, S. Ali] Johns Hopkins Sch Med, Kennedy Krieger Inst, Moser Ctr Leukodystrophies & Neurogenet Serv, Baltimore, MD USA. [van der Knaap, Marjo S.] Vrije Univ Amsterdam Med Ctr, Dept Child Neurol, Amsterdam, Netherlands. [van der Knaap, Marjo S.] Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Back, Stephen A.] Oregon Hlth & Sci Univ, Dept Pediat & Neurol, Portland, OR 97201 USA. [Damiani, Stephen] Mission Massimo Fdn Inc, Melbourne, Vic, Australia. [Damiani, Stephen] Mission Massimo Fdn Inc, Los Angeles, CA USA. [Goldman, Steven A.] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14642 USA. [Goldman, Steven A.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Takanohashi, Asako; Vanderver, Adeline] Childrens Natl Hlth Syst, Med Genet Res Ctr, Washington, DC USA. [Petryniak, Magdalena] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Portland, OR 97201 USA. [Rowitch, David] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Rowitch, David] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Messing, Albee] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [Messing, Albee] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53706 USA. [Wrabetz, Lawrence] SUNY Buffalo, Hunter James Kelly Res Inst HJRKI, Dept Neurol, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Wrabetz, Lawrence] SUNY Buffalo, Hunter James Kelly Res Inst HJRKI, Dept Biochem, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. [Eichler, Florian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Escolar, Maria L.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. [Vanderver, Adeline] George Washington Univ, Sch Med, Dept Integrated Syst Biol, Washington, DC USA. RP Vanderver, A (reprint author), Childrens Natl Hlth Syst, 111 Michigan Ave NW, Washington, DC 20001 USA. EM avanderv@childrensnational.org RI Escolar, Maria/J-3721-2016; Helman, Guy/C-7935-2017; OI Helman, Guy/0000-0002-4784-7423; Patterson, Marc/0000-0002-1116-126X FU Departments of Neurology and Genetics of the Children's National Health System; Delman Fund for Pediatric Neurology Education and Research FX The GLIA consensus meeting was funded in part by a grant from the Departments of Neurology and Genetics of the Children's National Health System and the members of the Leukodystrophy Alliance. Guy Heiman received support from the Delman Fund for Pediatric Neurology Education and Research. NR 81 TC 7 Z9 8 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2015 VL 114 IS 4 BP 527 EP 536 DI 10.1016/j.ymgme.2015.01.014 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA CG1BV UT WOS:000353008900005 PM 25684057 ER PT J AU Simon, JH Kinkel, RP Kollman, C O'Connor, P Fisher, E You, X Hyde, R AF Simon, J. H. Kinkel, R. P. Kollman, C. O'Connor, P. Fisher, E. You, X. Hyde, R. CA CHAMPIONS Investigators Grp TI Ten-year follow-up of the 'minimal MRI lesion' subgroup from the original CHAMPS Multiple Sclerosis Prevention Trial SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE CHAMPS; CHAMPIONS; disease progression; intramuscular interferon beta-1a; MRI; multiple sclerosis; clinically isolated syndrome ID CLINICALLY ISOLATED SYNDROMES; INTRAMUSCULAR INTERFERON BETA-1A; 1ST DEMYELINATING EVENT; DISABILITY; DEFINITE; MS; CONVERSION AB Background: Patients with clinically isolated syndrome (CIS) and characteristic magnetic resonance imaging (MRI) lesions are at high risk for multiple sclerosis (MS). However, patients with a minimal MRI lesion burden (a low T2-hyperintense [low T2] lesion count) may have borderline formal diagnostic criteria, presenting a clinical management challenge. Objective: Compare the 10-year disease progression of patients with low and higher T2 lesion counts treated over most intervals. Methods: CIS patients from the original CHAMPS MS trial were retrospectively assigned to low-T2 (first quartile; 2-8 lesions) or higher-T2 (second through fourth quartiles; 9 lesions) groups using baseline T2 lesion counts. The 5- and 10-year open-label extension of CHAMPS (CHAMPIONS) evaluated conversion to clinically definite MS (CDMS), MRI activity, relapses, and disability. Results: The vast majority of patients showed new disease activity by MRI and/or clinical criteria at 10 years (low-T2 86%; higher-T2 98%). Fewer low-T2 than higher-T2 patients developed CDMS (40% vs. 63%; p = 0.013); low-T2 patients also had fewer new brain lesions, less brain volume loss, and less disability progression. Conclusion: CIS patients with low T2 lesion counts show continued disease activity. However, all assessments of disease progression over 10 years indicated a significantly less severe disease course for low-T2 patients. C1 [Simon, J. H.] Portland VA Med Ctr, VA Med Ctr, Portland, OR 97239 USA. [Simon, J. H.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Kinkel, R. P.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Kollman, C.] Jaeb Ctr Hlth Res, Dept Biostat, Tampa, FL USA. [O'Connor, P.] St Michaels Hosp, Multiple Sclerosis Clin, Toronto, ON M5B 1W8, Canada. [Fisher, E.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44106 USA. [You, X.] Biogen Idec Inc, Dept Biostat, Cambridge, MA USA. [Hyde, R.] Biogen Idec Inc, Global Med Affairs, Cambridge, MA USA. RP Simon, JH (reprint author), Portland VA Med Ctr, VA Med Ctr, 3710 SW US Vet Rd, Portland, OR 97239 USA. EM jack.simon1@me.com NR 22 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD APR PY 2015 VL 21 IS 4 BP 415 EP 422 DI 10.1177/1352458514547407 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE9LH UT WOS:000352165000010 PM 25344370 ER PT J AU Barzel, B Barabasi, AL AF Barzel, Baruch Barabasi, Albert-Laszlo TI Silence on the relevant literature and errors in implementation reply SO NATURE BIOTECHNOLOGY LA English DT Letter ID REGULATORY NETWORKS; WIRES C1 [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Barzel, B (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu NR 21 TC 0 Z9 0 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2015 VL 33 IS 4 BP 339 EP 342 DI 10.1038/nbt.3184 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CF2AE UT WOS:000352348500014 PM 25850053 ER PT J AU Scholz, C Weinert, BT Wagner, SA Beli, P Miyake, Y Qi, J Jensen, LJ Streicher, W McCarthy, AR Westwood, NJ Lain, S Cox, J Matthias, P Mann, M Bradner, JE Choudhary, C AF Scholz, Christian Weinert, Brian T. Wagner, Sebastian A. Beli, Petra Miyake, Yasuyuki Qi, Jun Jensen, Lars J. Streicher, Werner McCarthy, Anna R. Westwood, Nicholas J. Lain, Sonia Cox, Juergen Matthias, Patrick Mann, Matthias Bradner, James E. Choudhary, Chunaram TI Acetylation site specificities of lysine deacetylase inhibitors in human cells SO NATURE BIOTECHNOLOGY LA English DT Article ID SISTER-CHROMATID COHESION; CYTOSCAPE PLUG-IN; HISTONE DEACETYLASE; HDAC INHIBITORS; GENE ONTOLOGY; PROTEIN; PROTEOMICS; TRANSCRIPTION; METABOLISM; MECHANISMS AB Lysine deacetylases inhibitors (KDACIs) are used in basic research, and many are being investigated in clinical trials for treatment of cancer and other diseases. However, their specificities in cells are incompletely characterized. Here we used quantitative mass spectrometry (MS) to obtain acetylation signatures for 19 different KDACIs, covering all 18 human lysine deacetylases. Most KDACIs increased acetylation of a small, specific subset of the acetylome, including sites on histones and other chromatin-associated proteins. Inhibitor treatment combined with genetic deletion showed that the effects of the pan-sirtuin inhibitor nicotinamide are primarily mediated by SIRT1 inhibition. Furthermore, we confirmed that the effects of tubacin and bufexamac on cytoplasmic proteins result from inhibition of HDAC6. Bufexamac also triggered an HDAC6-independent, hypoxia-like response by stabilizing HIF1-alpha, providing a possible mechanistic explanation of its adverse, pro-inflammatory effects. Our results offer a systems view of KDACI specificities, providing a framework for studying function of acetylation and deacetylases. C1 [Scholz, Christian; Weinert, Brian T.; Wagner, Sebastian A.; Beli, Petra; Choudhary, Chunaram] Univ Copenhagen, Fac Hlth & Med Sci, Dept Prote, Novo Nordisk Fdn,Ctr Prot Res, Copenhagen, Denmark. [Miyake, Yasuyuki; Matthias, Patrick] Friedrich Miescher Inst Biomed Res, Basel, Switzerland. [Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jensen, Lars J.] Univ Copenhagen, Fac Hlth Sci, Dept Prot Sci & Technol, Novo Nordisk Fdn,Ctr Prot Res, Copenhagen, Denmark. [Streicher, Werner] Univ Copenhagen, Fac Hlth Sci, Dept Dis Syst Biol, Novo Nordisk Fdn,Ctr Prot Res, Copenhagen, Denmark. [McCarthy, Anna R.; Lain, Sonia] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Westwood, Nicholas J.] Univ St Andrews, EaStCHEM, Sch Chem, St Andrews, Fife, Scotland. [Westwood, Nicholas J.] Univ St Andrews, EaStCHEM, St Andrews, Fife, Scotland. [Cox, Juergen; Mann, Matthias] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany. RP Choudhary, C (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Dept Prote, Novo Nordisk Fdn,Ctr Prot Res, Copenhagen, Denmark. EM chuna.choudhary@cpr.ku.dk RI Lain, Sonia/B-6980-2014; OI Lain, Sonia/0000-0001-9693-5246; Weinert, Brian/0000-0002-1335-9915; Jensen, Lars Juhl/0000-0001-7885-715X; Beli, Petra/0000-0001-9507-9820 FU Novo Nordisk Foundation [NNF14CC0001]; Danish Research Council [FSS: 10-085134, FSS: 12-12610]; EMBO Young Investigator program; Doris Duke Charitable Foundation FX We thank the members of the department of proteomics at CPR for their helpful discussions. We thank T. Narita for providing help with bioinformatic analyses. We thank R. Lavallee, D. Bekker-Jensen, H.C. Grell and B. Smith for their technical support. We gratefully acknowledge M. W. McBurney for providing SIRT1 knockout MEFs, D. Reinberg for providing SIRT2 knockout MEFs, and R. Mostoslavsky for providing SIRT6 knockout MEFs. This work was supported by the Hallas Moller Investigator grant from the Novo Nordisk Foundation to C.C. S.A.W. and P.B. were supported by individual postdoctoral grants from the Danish Research Council (FSS: 10-085134, FSS: 12-12610). C.C. is supported by the EMBO Young Investigator program. The Center for Protein Research is supported by a generous grant from the Novo Nordisk Foundation (grant no. NNF14CC0001). J.E.B. is supported by a grant from the Doris Duke Charitable Foundation. We thank the PRIDE team for their support with data storage. NR 65 TC 49 Z9 51 U1 10 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2015 VL 33 IS 4 BP 415 EP U136 DI 10.1038/nbt.3130 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CF2AE UT WOS:000352348500029 PM 25751058 ER PT J AU Power, MC Weuve, J Sharrett, AR Blacker, D Gottesman, RF AF Power, Melinda C. Weuve, Jennifer Sharrett, A. Richey Blacker, Deborah Gottesman, Rebecca F. TI Statins, cognition, and dementia-systematic review and methodological commentary SO NATURE REVIEWS NEUROLOGY LA English DT Review ID MARGINAL STRUCTURAL MODELS; COA REDUCTASE INHIBITORS; MIDDLE-AGED ADULTS; ALZHEIMERS-DISEASE; INCIDENT DEMENTIA; CHOLESTEROL-METABOLISM; CARDIOVASCULAR HEALTH; CEREBROSPINAL-FLUID; BRAIN CHOLESTEROL; CLINICAL-EVIDENCE AB Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential. C1 [Power, Melinda C.; Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Weuve, Jennifer] Rush Inst Hlth Aging, Dept Internal Med, Chicago, IL 60612 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gottesman, Rebecca F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Gottesman, RF (reprint author), Johns Hopkins Sch Med, Dept Neurol, 733 North Broadway, Baltimore, MD 21205 USA. EM rgottesm@jhmi.edu FU National Institute on Aging [T32 AG027668]; Alzheimer's Drug Discovery Foundation (ADDF) FX M.C.P. receives a grant from the National Institute on Aging (T32 AG027668). Funding was provided to M.C.P., J.W. and D.B. from the Alzheimer's Drug Discovery Foundation (ADDF). The ADDF catalyses and funds drug discovery and drug development for Alzheimer disease (AD) and related disorders. To learn more about the ADDF, visit the website at www.alzdiscovery.org. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. This work has not previously been presented in any form. However, the literature review and quality assessment were completed in parallel with work completed for the AlzRisk website (www.alzrisk.org), which attempts to catalogue epidemiological reports on risk factors for AD and to provide a continually updated, publically available assessment of the state of the literature. The AlzRisk database entry on statins, which is currently limited to studies reporting on AD as an end point, will be updated as new studies are published. We would like to thank John Jackson for his work in developing AlzRisk search strategies, which informed our search strategy, and his insight into the accuracy of electronic medical records in ascertaining dementia status. NR 91 TC 12 Z9 12 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD APR PY 2015 VL 11 IS 4 BP 220 EP 229 DI 10.1038/nrneurol.2015.35 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CF2BH UT WOS:000352351700007 PM 25799928 ER PT J AU Sanchez, A Wszolek, MF AF Sanchez, Alejandro Wszolek, Matthew F. TI Quality of life in patients with non-muscle-invasive bladder cancer SO NATURE REVIEWS UROLOGY LA English DT Editorial Material ID TRANSURETHRAL RESECTION; SELECTIVE BLADDER; THERAPY; CHEMOTHERAPY; CONSERVATION; MANAGEMENT; RADIATION; OUTCOMES; IMPACT C1 [Sanchez, Alejandro; Wszolek, Matthew F.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Wszolek, MF (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM mwszolek@partners.org NR 9 TC 1 Z9 1 U1 4 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 EI 1759-4820 J9 NAT REV UROL JI Nat. Rev. Urol. PD APR PY 2015 VL 12 IS 4 DI 10.1038/nrurol.2015.12 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CF4CI UT WOS:000352495700002 ER PT J AU Wiley, CA Bonneh-Barkay, D Dixon, CE Lesniak, A Wang, GJ Bissel, SJ Kochanek, PM AF Wiley, Clayton A. Bonneh-Barkay, Dafna Dixon, C. Edward Lesniak, Andrew Wang, Guoji Bissel, Stephanie J. Kochanek, Patrick M. TI Role for mammalian chitinase 3-like protein 1 in traumatic brain injury SO NEUROPATHOLOGY LA English DT Article DE BRP-39; chitinase 3-like protein 1; controlled cortical impact; neuroinflammation; traumatic brain injury ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NERVOUS-SYSTEM INFLAMMATION; REACTIVE ASTROCYTES; TRANSGENIC INHIBITION; YKL-40 EXPRESSION; MICE; TISSUE; DEGENERATION; DISEASES; EVOLUTION AB Traumatic brain injury (TBI) is accompanied by inflammatory infiltrates and CNS tissue response. The astrocytosis associated with TBI has been proposed to have both beneficial and detrimental effects on surviving neural tissue. We recently observed prominent astrocytic expression of YKL-40/chitinase 3-like protein 1 (CHI3L1) associated with severity of brain injury. The physiological role of CHI3L1 in the CNS is unknown; however, its distribution at the perimeter of contusions and temporal course of expression suggested that in TBI it might be an important component of the astrocytic response to modulate CNS inflammation. To address this hypothesis, we used serially sectioned brains to quantitatively compare the neuropathological outcomes of TBI produced by controlled cortical impact in wild type (WT) and chi3l1 knockout (KO) mice where the murine YKL-40 homologue, breast regression protein 39 (BRP-39/CHI3l1), had been homozygously disrupted. At 21 days post-injury, chi3l1KO mice displayed greater astrocytosis (increased GFAP staining) in the hemispheres ipsilateral and contralateral to impact compared with WT mice. Similarly, Iba1 expression as a measure of microglial/macrophage response was significantly increased in chi3l1KO compared with WT in the hemisphere contralateral to impact. We conclude that astrocytic expression of CHI3L1 limits the extent of both astrocytic and microglial/macrophage facets of neuroinflammation and suggests a novel potential therapeutic target for modulating neuroinflammation. C1 [Wiley, Clayton A.; Bonneh-Barkay, Dafna; Lesniak, Andrew; Wang, Guoji; Bissel, Stephanie J.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Dixon, C. Edward] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Dept Neurosurg Anesthesiol, Pittsburgh, PA 15213 USA. [Dixon, C. Edward] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Dixon, C. Edward] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Dept Crit Care Med, Pittsburgh, PA 15213 USA. [Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Neurosurg Anesthesiol, Pittsburgh, PA 15213 USA. [Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Dixon, C. Edward; Kochanek, Patrick M.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15213 USA. [Kochanek, Patrick M.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Anesthesiol & Pediat, Pittsburgh, PA 15213 USA. RP Wiley, CA (reprint author), Univ Pittsburgh, Dept Pathol, S701 Scaife Hall 200 Lothrop, Pittsburgh, PA 15213 USA. EM wiley1@pitt.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NIH NINDS [NS 070003, NS079061, NS 30318, K24 MH01717]; Pittsburgh Foundation Emmerling funds FX We thank Mark Stauffer, Arlene Carbone-Wiley and Advait Salgarkar for valuable technical assistance. This work was supported, partly by funds from NIH NINDS NS 070003 to PMK; NS079061 to CED; NS 30318 to CED and PMK; K24 MH01717 to CAW, and Pittsburgh Foundation Emmerling funds to DB-B. NR 38 TC 6 Z9 6 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-6544 EI 1440-1789 J9 NEUROPATHOLOGY JI Neuropathology PD APR PY 2015 VL 35 IS 2 BP 95 EP 106 DI 10.1111/neup.12158 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CF5WV UT WOS:000352628900001 PM 25377763 ER PT J AU Boehm, JK Hernandez, R Boehm, JK Huffman, JC Smith, TW AF Boehm, Julia K. Hernandez, Rosalba Boehm, Julia K. Huffman, Jeffery C. Smith, Timothy W. TI Beyond risk factors & disease: Positive psychological well-being and cardiovascular health SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-Psychosomatic-Society CY MAR 18-21, 2015 CL Savannah, GA SP Amer Psychosomat Soc C1 [Boehm, Julia K.; Boehm, Julia K.] Chapman Univ, Psychol, Orange, CA USA. [Hernandez, Rosalba] Univ Illinois, Sch Social Work, Urbana, IL USA. [Huffman, Jeffery C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. [Smith, Timothy W.] Univ Utah, Psychol, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2015 VL 77 IS 3 MA 2538 BP A15 EP A15 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CF9CU UT WOS:000352860000051 ER PT J AU Huffman, JC Beale, EE Moore, SV Belcher, AM Suarez, L Beach, SR Celano, CM Gaggin, HK Motiwala, SR Gandhi, PU Januzzi, JL AF Huffman, Jeffery C. Beale, Eleanor E. Moore, Shannon V. Belcher, Arianna M. Suarez, Laura Beach, Scott R. Celano, Christopher M. Gaggin, Hanna K. Motiwala, Shweta R. Gandhi, Parul U. Januzzi, James L. TI The connection between positive psychological constructs, biology, and behavior: results from the GRACE study SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-Psychosomatic-Society CY MAR 18-21, 2015 CL Savannah, GA SP Amer Psychosomat Soc C1 [Huffman, Jeffery C.; Beach, Scott R.; Celano, Christopher M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. [Beale, Eleanor E.; Moore, Shannon V.; Suarez, Laura] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Belcher, Arianna M.; Gandhi, Parul U.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. [Gaggin, Hanna K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol, Boston, MA USA. [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Cardiol, Boston, MA 02215 USA. [Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2015 VL 77 IS 3 MA 2573 BP A16 EP A16 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CF9CU UT WOS:000352860000054 ER PT J AU De la Marche, W Noens, I Boets, B Kuppens, S Steyaert, J AF De la Marche, Wouter Noens, Ilse Boets, Bart Kuppens, Sofie Steyaert, Jean TI The underlying symptom structure of autism spectrum disorders: A factor analytic approach using the developmental, dimensional and diagnostic interview SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; DSM-5; Factor analysis; 3di ID REPETITIVE BEHAVIORS; INTERESTS DOMAIN; DSM-5 CRITERIA; PHENOTYPE; CHILDREN; VALIDITY; TRAITS; MODEL; HETEROGENEITY; SAMPLES AB Several studies have focused on the underlying symptom structure of Autism Spectrum Disorders (ASD), but results have been equivocal. We performed a confirmatory factor analysis on data of the Developmental, Dimensional and Diagnostic Interview of 275 participants with ASD between 3 and 23 years of age, aimed at strengthening the empirical evidence of previously published factor structure solutions using the same instrument. As none of these hypothesised models fitted our data, an exploratory factor analysis was undertaken. Results pointed towards a five factor model. A 'Restricted and Repetitive Behaviour and Interest' factor could be separated from 'Shaking and Nodding', 'Emotional Reciprocity' and two other factors that both represented deficits in social interaction and communication. Although not completely confirming, our results are generally in favour of the present DSM-5 criteria. By showing that the items did not fully segregate according to theoretically postulated subdomains, we offer a possible explanation for the heterogeneity in proposed factor structures for ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [De la Marche, Wouter; Noens, Ilse; Boets, Bart; Steyaert, Jean] Univ Leuven, KU Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [De la Marche, Wouter] Publ Psychiat Care Ctr Geel, Youth Dept, Leuven, Belgium. [Noens, Ilse] Univ Leuven, KU Leuven, Parenting & Special Educ Res Unit, Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Boets, Bart; Steyaert, Jean] Univ Leuven, KU Leuven, Child & Adolescent Psychiat Dept, Leuven, Belgium. [Kuppens, Sofie] Univ Leuven, KU Leuven, HIVA Res Inst Work & Soc, Leuven, Belgium. [Steyaert, Jean] Maastricht Univ Hosp, Clin Genet, Maastricht, Netherlands. RP Steyaert, J (reprint author), UPC KU Leuven Campus Gasthuisberg, Child & Adolescent Psychiat Dept, Herestr 49, B-3000 Leuven, Belgium. EM wouter.delamarche@opzgeel.be; jean.steyaert@uz.kuleuven.be FU Research Foundation Flanders-FWO [G.0609.07]; Research Council of the KU Leuven [IDO/08/013] FX This research was supported by the Research Foundation Flanders-FWO (grant number G.0609.07 to JS; BB is Postdoctoral Fellow of the FWO) and by a grant from the Research Council of the KU Leuven (IDO/08/013). NR 44 TC 2 Z9 2 U1 3 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD APR PY 2015 VL 12 BP 40 EP 51 DI 10.1016/j.rasd.2014.11.002 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA CF9ZH UT WOS:000352925900005 ER PT J AU Gaissert, H AF Gaissert, Henning TI Thymectomy: A Trivalent Surgical Approach? SO THORACIC AND CARDIOVASCULAR SURGEON LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Gaissert, H (reprint author), Massachusetts Gen Hosp, Dept Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0171-6425 EI 1439-1902 J9 THORAC CARDIOV SURG JI Thorac. Cardiovasc. Surg. PD APR PY 2015 VL 63 IS 3 BP 176 EP 177 DI 10.1055/s-0035-1549282 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CG1IJ UT WOS:000353026000002 PM 25875857 ER PT J AU Wolf, E Lin, CY Eilers, M Levens, DL AF Wolf, Elmar Lin, Charles Y. Eilers, Martin Levens, David L. TI Taming of the beast: shaping Myc-dependent amplification SO TRENDS IN CELL BIOLOGY LA English DT Review DE Myc; cancer; transcription ID ARF TUMOR-SUPPRESSOR; RIBOSOMAL-PROTEIN L11; EMBRYONIC STEM-CELLS; C-MYC; TRANSCRIPTION FACTORS; ESSENTIAL COFACTOR; DIRECT ACTIVATION; CELLULAR GROWTH; DROSOPHILA-MYC; CAD PROMOTER AB Myc deregulation is a hallmark oncogenic event where overexpression of the transcription factor gives rise to numerous tumorigenic phenotypes. The complex consequences of Myc deregulation have prevented clear mechanistic interpretations of its function. A synthesis of recent experimental observations offers a consensus on the direct transcriptional function of Myc: when overexpressed, Myc broadly engages the established euchromatic cis-regulatory landscape of the cell, where the factor generally amplifies transcription. The level of Myc binding at target genes and the transcriptional output are differentially modulated by additional regulators, including Miz 1. Targeting Myc oncogenic activity will require an understanding of whether amplification promotes tumorigenesis and the consequences of amplification in tumors adapted to oncogenic Myc. C1 [Wolf, Elmar; Eilers, Martin] Univ Wurzburg, Theodor Boveri Inst, Bioctr, D-97074 Wurzburg, Germany. [Wolf, Elmar; Eilers, Martin] Univ Wurzburg, Ctr Comprehens Canc, D-97074 Wurzburg, Germany. [Lin, Charles Y.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Levens, David L.] Pathol Lab, Bethesda, MD 20892 USA. RP Lin, CY (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Charles_lin@dfci.harvard.edu; martin.eilers@biozentrum.uni-wuerzburg.de; levens@helix.nih.gov RI Levens, David/C-9216-2009; OI Levens, David/0000-0002-7616-922X; Eilers, Martin/0000-0002-0376-6533; Wolf, Elmar/0000-0002-5299-6335 FU Intramural NIH HHS [ZIA BC011465-03, Z99 CA999999] NR 66 TC 25 Z9 25 U1 2 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD APR PY 2015 VL 25 IS 4 BP 241 EP 248 DI 10.1016/j.tcb.2014.10.006 PG 8 WC Cell Biology SC Cell Biology GA CF6QD UT WOS:000352680300008 PM 25475704 ER PT J AU Gimenez-Cassina, A Danial, NN AF Gimenez-Cassina, Alfredo Danial, Nike N. TI Regulation of mitochondrial nutrient and energy metabolism by BCL-2 family proteins SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review DE BCL-2 proteins; mitochondria; OXPHOS; glucose; fatty acids; metabolism ID CARNITINE PALMITOYLTRANSFERASE I; FATTY-ACID OXIDATION; CELL-DEATH; OUTER-MEMBRANE; KETOGENIC DIET; BAX OLIGOMERIZATION; INSULIN-SECRETION; RESPIRATORY-CHAIN; VDAC STRUCTURE; BETA-CELLS AB Cells have evolved a highly integrated network of mechanisms to coordinate cellular survival/death, proliferation, differentiation, and repair with metabolic states. It is therefore not surprising that proteins with canonical roles in cell death/survival also modulate nutrient and energy metabolism and vice versa. The finding that many BCL-2 (B cell lymphoma 2) proteins reside at mitochondria or can translocate to this organelle has long motivated investigation into their involvement in normal mitochondrial physiology and metabolism. These endeavors have led to the discovery of homeostatic roles for BCL-2 proteins beyond apoptosis. We predominantly focus on recent findings that link select BCL-2 proteins to carbon substrate utilization at the level of mitochondrial fuel choice, electron transport, and metabolite import independent of their cell death regulatory function. C1 [Gimenez-Cassina, Alfredo; Danial, Nike N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Gimenez-Cassina, Alfredo; Danial, Nike N.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Gimenez-Cassina, A (reprint author), Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden. EM alfredo.gimenez-cassina@ki.se; nika_danial@dfci.harvard.edu OI Gimenez-Cassina, Alfredo/0000-0002-2768-2350 FU US National Institutes of Health (NIH) [R01DK078081, R01NS083844]; Juvenile Diabetes Research Foundation [17-2011-595]; Hjarnfonden (Swedish Brain Foundation) [FO2014-0257]; Petrus och Augusta Hedlunds Foundation [M-59-2014]; Ake Wibergs Foundation [M14-0112] FX The authors would like to thank Eric Smith for part of the graphics in this article. This work was supported by the US National Institutes of Health (NIH) grants R01DK078081 and R01NS083844 (N.N.D.), Juvenile Diabetes Research Foundation grant 17-2011-595 (N.N.D.), Hjarnfonden (Swedish Brain Foundation) grant FO2014-0257 (A.G-C.), Petrus och Augusta Hedlunds Foundation grant M-59-2014 (A.G-C.), and Ake Wibergs Foundation grant M14-0112 (A.G-C.). NR 102 TC 9 Z9 11 U1 3 U2 13 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 2015 VL 26 IS 4 BP 165 EP 175 DI 10.1016/j.tem.2015.02.004 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG2DP UT WOS:000353085400002 PM 25748272 ER PT J AU Govani, SM Waljee, AK Stidham, RW Higgins, PDR AF Govani, Shail M. Waljee, Akbar K. Stidham, Ryan W. Higgins, Peter D. R. TI Increasing ultraviolet light exposure is associated with reduced mortality from Clostridium difficile infection SO UNITED EUROPEAN GASTROENTEROLOGY JOURNAL LA English DT Article DE Clostridium difficile; colitis; infectious disease; mortality; risk factors; seasonality; ultraviolet light; vitamin D ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; VITAMIN-D DEFICIENCY; RETROSPECTIVE COHORT; RISK; SUPPRESSION; INDEX AB Background: Clostridium difficile infection (CDI) is an increasingly common cause of inpatient mortality. Vitamin D deficiency is associated with more aggressive CDI. We aimed to determine if average annual ultraviolet light (UV) exposure was associated with mortality in patients with CDI. Methods: We used the US National Inpatient Sample (NIS) from 2004-2011 to assess the mortality risk in patients with a diagnosis of CDI (as per ICD-9CM 008.45). Annual average state UV exposure was assigned to each hospitalization. Logistic regression was used to determine the effects of UV exposure on mortality, controlling for age, gender, race and other comorbidities. Results: During the study period, there were 2.61 million hospitalizations with a diagnosis of CDI. The mortality rate was 9.0%. In univariate analysis, the odds ratio (OR) of inpatient mortality for the UV index was 0.97 (95% CI 0.95-0.99; p=0.008) per unit of UV exposure. In a multivariable model adjusting for age, gender, race, Charlson-Deyo index, season and coexisting inflammatory bowel disease, the UV index remained a protective predictor, with an OR of 0.94 (95% CI 0.92-0.96; p<0.001). In the multivariate model, a seasonal effect was also present, with the highest risk of inpatient mortality in the period from January to March (OR 1.11; 95% CI 1.08-1.14) and the lowest risk, from July to September (OR 0.95; 95% CI 0.92-0.98). Conclusions: An increase in UV exposure index is associated with a reduced risk of inpatient mortality in patients with CDI. A seasonal effect is also present, with the highest risk of death during winter months. Further studies exploring the role of UV light in CDI are necessary. C1 [Govani, Shail M.; Waljee, Akbar K.; Stidham, Ryan W.; Higgins, Peter D. R.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Waljee, Akbar K.] US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA. RP Govani, SM (reprint author), 3912 Taubman Ctr,1500 E Med Ctr Dr,SPC 5362, Ann Arbor, MI 48109 USA. EM shailg@umich.edu RI Waljee, Akbar/G-2067-2010 OI Waljee, Akbar/0000-0003-1964-8790 FU Inflammatory Bowel Disease Working Group; UCB Inc; US Veterans' Administration [1IK2HX000775] FX This work was supported by the Inflammatory Bowel Disease Working Group through an unrestricted educational grant by UCB Inc (GI Fellows Research Award to SMG) and the US Veterans' Administration (VA HSR&D CDA-2 Career Development Award number 1IK2HX000775, to AKS). NR 23 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2050-6406 EI 2050-6414 J9 UNITED EUR GASTROENT JI United European Gastroenterol. J. PD APR PY 2015 VL 3 IS 2 SI SI BP 208 EP 214 DI 10.1177/2050640614567185 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE9LY UT WOS:000352166700013 PM 25984339 ER PT J AU Underhill, M Roper, K Siefert, ML Boucher, J Berry, D AF Underhill, Meghan Roper, Kristin Siefert, Mary Lou Boucher, Jean Berry, Donna TI Evidence-Based Practice Beliefs and Implementation Before and After an Initiative to Promote Evidence-Based Nursing in an Ambulatory Oncology Setting SO WORLDVIEWS ON EVIDENCE-BASED NURSING LA English DT Article DE evidence-based practice; nursing; cancer care ID HEALTH-CARE; NURSES; BARRIERS; QUALITY AB BackgroundThe purpose of evidence-based practice (EBP) in nursing is to improve patient outcomes, providing the best and most up-to-date care practices. In 2011, a nurse-led committee convened to develop an institute-wide initiative to promote EBP with oncology nurses at the Dana-Farber Cancer Institute. AimsCompare and describe oncology nurse beliefs and perceived implementation of EBP and explore beliefs and implementation before and after implementing an institutional EBP initiative. MethodsBased on the Advancing Research and Clinical practice through close Collaboration (ARCC) Model, the Evidence-Based Practice Beliefs (EBP-B) and Implementation (EBP-I) scales were distributed to all Dana-Farber Cancer Institute registered and advanced practice nurses through an online survey in 2011 (T1) and again in 2013 (T2) after the implementation of an institute-wide nursing EBP initiative (orientation, poster presentations, education). Descriptive and correlation statistics were completed on total scores and demographics. Differences in beliefs and implementation scores based on demographics were analyzed with Mann-Whitney U tests. Open-ended item responses at each time point (T) were summarized for EBP barriers and promoters. FindingsThirty-two percent (n = 112 at T1; n = 113 at T2) of 350 nurses began the survey. A history of formal EBP education and nurse role were associated with higher EBP-B and EBP-I scores (p < .05). Highest level of education was significantly correlated with both EBP-B (r = .25; p = .03) and EBP-I (r = .32; p = .01). Narrative responses to open-ended questions described perceived personal and environmental barriers to engaging in EBP. Linking Evidence to ActionAlthough no significant differences were noted in beliefs and implementation after the EBP initiative, nurses reported valuing EBP. Respondents acknowledged a lack of full preparation in the EBP process to engage in and implement EBP consistently. Nurse role, formal EBP education, and highest level of education were associated with perceptions of EBP beliefs and implementation. Nurses should be provided the mentorship and support to obtain continuing education about how to engage in EBP and about implementing EBP change. C1 [Underhill, Meghan; Roper, Kristin; Boucher, Jean; Berry, Donna] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Underhill, Meghan; Berry, Donna] Harvard Univ, Sch Med, Boston, MA USA. [Siefert, Mary Lou] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Ctr Clin & Profess Dev, Boston, MA 02115 USA. [Boucher, Jean] Univ Massachusetts Worcester, Grad Sch Nursing, Nursing & Med, Worcester, MA USA. RP Underhill, M (reprint author), Dana Farber Canc Inst, Phyllis F Canter Ctr, 450 Brookline Ave, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu NR 24 TC 4 Z9 4 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-102X EI 1741-6787 J9 WORLDV EVID-BASED NU JI Worldviews Evid.-Based Nurs. PD APR PY 2015 VL 12 IS 2 BP 70 EP 78 DI 10.1111/wvn.12080 PG 9 WC Nursing SC Nursing GA CF5BD UT WOS:000352568700002 PM 25704058 ER PT J AU AlJaroudi, WA Refaat, MM Habib, RH Al-Shaar, L Singh, M Gutmann, R Bloom, HL Dudley, SC Ellinor, PT Saba, SF Shalaby, AA Weiss, R McNamara, DM Halder, I London, B AF AlJaroudi, Wael A. Refaat, Marwan M. Habib, Robert H. Al-Shaar, Laila Singh, Madhurmeet Gutmann, Rebecca Bloom, Heather L. Dudley, Samuel C. Ellinor, Patrick T. Saba, Samir F. Shalaby, Alaa A. Weiss, Raul McNamara, Dennis M. Halder, Indrani London, Barry CA Genetic Risk Assessment Defibrilla TI Effect of Angiotensin-Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock in Patients With Severe Systolic Heart Failure (from the GRADE Multicenter Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; DEATH; MORTALITY; ENALAPRIL; FIBROSIS; PREVENTION; TRIAL; MORBIDITY AB Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of <= 30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR 30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2). (C) 2015 Elsevier Inc. All rights reserved. C1 [AlJaroudi, Wael A.; Refaat, Marwan M.] Amer Univ Beirut, Med Ctr, Div Cardiovasc Med, Beirut, Lebanon. [Habib, Robert H.; Al-Shaar, Laila] Amer Univ Beirut, Med Ctr, Vasc Med Program, Beirut, Lebanon. [Habib, Robert H.; Al-Shaar, Laila] Dept Internal Med, Outcomes Res Unit, Beirut, Lebanon. [Singh, Madhurmeet; Saba, Samir F.; Shalaby, Alaa A.; McNamara, Dennis M.; Halder, Indrani] Univ Pittsburgh, Sch Med, Div Cardiol, Pittsburgh, PA USA. [Gutmann, Rebecca; London, Barry] Univ Iowa, Carver Coll Med, Div Cardiovasc Med, Iowa City, IA USA. [Bloom, Heather L.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Dudley, Samuel C.] Brown Univ, Warren Alpert Med Sch, Div Cardiol, Providence, RI 02912 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Shalaby, Alaa A.] Vet Affairs Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA USA. [Weiss, Raul] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. RP Refaat, MM (reprint author), Amer Univ Beirut, Med Ctr, Div Cardiovasc Med, Beirut, Lebanon. EM mr48@aub.edu.lb FU National Heart, Lung, and Blood Institute [R01 HL77398] FX This study was supported by a research grant #R01 HL77398 from the National Heart, Lung, and Blood Institute. NR 27 TC 7 Z9 7 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2015 VL 115 IS 7 BP 924 EP 931 DI 10.1016/j.amjcard.2015.01.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RX UT WOS:000352253000013 PM 25682436 ER PT J AU Benacerraf, BR Abuhamad, AZ Bromley, B Goldstein, SR Groszmann, Y Shipp, TD Timor-Tritsch, IE AF Benacerraf, Beryl R. Abuhamad, Alfred Z. Bromley, Bryann Goldstein, Steven R. Groszmann, Yvette Shipp, Thomas D. Timor-Tritsch, Ilan E. TI Consider ultrasound first for imaging the female pelvis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE female pelvis; tenderness guided imaging; 3D ultrasound imaging ID GUIDED TRANSVAGINAL ULTRASONOGRAPHY; MULLERIAN DUCT ANOMALIES; 3-DIMENSIONAL ULTRASOUND; EXTERNAL VALIDATION; DEEP ENDOMETRIOSIS; ADNEXAL MASSES; OVARIAN-CANCER; DIAGNOSIS; SONOGRAPHY; ACCURACY AB Ultrasound technology has evolved dramatically in recent years and now includes applications such as 3-dimensional volume imaging, real-time evaluation of pelvic organs (simultaneous with the physical examination), and Doppler blood flow mapping without the need for contrast, which makes ultrasound imaging unique for imaging the female pelvis. Among the many cross-sectional imaging techniques, we should use the most informative, less invasive, and less expensive modality to avoid radiation when possible. Hence, ultrasound imaging should be the first imaging modality used in women with pelvic symptoms. C1 [Benacerraf, Beryl R.; Bromley, Bryann; Groszmann, Yvette; Shipp, Thomas D.] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Benacerraf, Beryl R.; Bromley, Bryann; Groszmann, Yvette; Shipp, Thomas D.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, Beryl R.; Bromley, Bryann; Shipp, Thomas D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benacerraf, Beryl R.; Bromley, Bryann] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Benacerraf, Beryl R.; Bromley, Bryann; Groszmann, Yvette; Shipp, Thomas D.] Diagnost Ultrasound Associates, Brookline, MA USA. [Abuhamad, Alfred Z.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Goldstein, Steven R.; Timor-Tritsch, Ilan E.] NYU, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY USA. NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. RP Benacerraf, BR (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM dua.ultrasound@gmail.com OI Timor-Tritsch, Ilan/0000-0001-9774-3107 NR 29 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2015 VL 212 IS 4 BP 450 EP 455 DI 10.1016/j.ajog.2015.02.015 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CE9EQ UT WOS:000352147100005 PM 25841638 ER PT J AU Minkoff, H Ecker, J AF Minkoff, Howard Ecker, Jeffrey TI Physicians' obligations to patients infected with Ebola: echoes of acquired immune deficiency syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE duty to care; Ebola; ethics; risk ID AIDS AB Physicians across the United States are engaged in training in the identification, isolation, and initial care of patients with Ebola. Some will be asked to do more. The issue this viewpoint will address is the moral obligation of physicians to participate in these activities. In order to do so the implicit contract between society and its physicians will be considered, as will many of the arguments that are redolent of those that were litigated 30 years ago when acquired immune deficiency syndrome (AIDS) was raising public fears to similar levels, and some physicians were publically proclaiming their unwillingness to render care to those individuals. We will build the case that if steps are taken to reduce risk-optimal personal protective equipment and training-to what is essentially the lowest possible level then rendering care should be seen as obligatory. If not, as in the AIDS era there will be an unfair distribution of risk, with those who take their obligations seriously having to go beyond their fair measure of exposure. It would also potentially undermine patients' faith in the altruism of physicians and thereby degrade the esteem in which our profession is held and the trust that underpins the therapeutic relationship. Finally there is an implicit contract with society. Society gives tremendously to us; we encumber a debt from all society does and offers, a debt for which recompense is rarely sought. The mosaic of moral, historical, and professional imperatives to render care to the infected all echoes the words of medicine's moral leaders in the AIDS epidemic. Arnold Relman perhaps put it most succinctly, "the risk of contracting the patient's disease is one of the risks that is inherent in the profession of medicine. Physicians who are not willing to accept that risk. ought not be in the practice of medicine." C1 [Minkoff, Howard] Suny Downstate Med Ctr, Maimonides Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. [Ecker, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA. RP Minkoff, H (reprint author), Suny Downstate Med Ctr, Maimonides Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. EM hminkoff@maimonidesmed.org NR 11 TC 3 Z9 3 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2015 VL 212 IS 4 BP 456 EP U486 AR 456.e1 DI 10.1016/j.ajog.2014.12.026 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CE9EQ UT WOS:000352147100006 PM 25530596 ER PT J AU McCoy, TH Castro, VM Rosenfield, HR Cagan, A Kohane, IS Perlis, RH AF McCoy, Thomas H. Castro, Victor M. Rosenfield, Hannah R. Cagan, Andrew Kohane, Isaac S. Perlis, Roy H. TI A Clinical Perspective on the Relevance of Research Domain Criteria in Electronic Health Records SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RDOC; FRAMEWORK; MODEL AB Objective: The limitations-of the DSM nosology for capturing dimensionality and overlap in psychiatric syndromes, and its poor correspondence to underlying neurobiology, have been well established. The Research Domain Criteria (RDoC), a proposed dimensional model of psychopathology, may offer new insights into psychiatric illness. For psychiatric clinicians, however, because tools for capturing these domains in clinical practice have not yet been established, the relevance and means of transition from the categorical system of DSM-5 to the dimensional models of RDoC remains unclear. The authors explored a method of extracting these dimensions from existing electronic health record (EHR) notes. Method: The authors used information retrieval and natural language processing methods to extract estimates of the RDoC dimensions in the EHRs of a large health system. They parsed and scored EHR documentation for 2,484 admissions covering 2,010 patients admitted to a psychiatric inpatient unit between 2011 and 2013. These domain scores were compared with DSM-IV-based ICD-9 codes to assess face validity. As a measure of predictive validity, these scores were examined for association with two outcomes: length of hospital stay and time to all-cause hospital readmission. Together, these analyses were intended to address the extent to which RDoC symptom domains might capture clinical features already available in narrative notes but not reflected in DSM diagnoses. Results: In mixed-effects models, loadings for the RDoC cognitive and arousal domains were associated with length of hospital stay, while the negative valence and social domains were associated with hazard of all-cause hospital readmission. Conclusions: These findings show that a computationally derived tool based on RDoC workgroup reports identifies symptom distributions in clinician notes beyond those captured by ICD-9 codes, and these domains have significant predictive validity. More generally, they point to the possibility that clinicians already document RDoC-relevant symptoms, albeit not in a quantified form. C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. EM rperlis@mgh.harvard.edu OI McCoy, Thomas/0000-0002-5624-0439 FU NIMH [MH086026, 5R25MH094612]; Stanley Center for Psychiatric Research at the Broad Institute FX Dr Perlis is supported by NIMH grant MH086026 and the Stanley Center for Psychiatric Research at the Broad Institute. Dr. McCoy is a participant in NIMH grant 5R25MH094612. NR 21 TC 4 Z9 4 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2015 VL 172 IS 4 BP 316 EP 320 DI 10.1176/appi.ajp.2014.14091177 PG 5 WC Psychiatry SC Psychiatry GA CE8TS UT WOS:000352117600006 PM 25827030 ER PT J AU Castro, VM Minnier, J Murphy, SN Kohane, I Churchill, SE Gainer, V Cai, TX Hoffnagle, AG Dai, Y Block, S Weill, SR Nadal-Vicens, M Pollastri, AR Rosenquist, JN Goryachev, S Ongur, D Sklar, P Perlis, RH Smoller, JW AF Castro, Victor M. Minnier, Jessica Murphy, Shawn N. Kohane, Isaac Churchill, Susanne E. Gainer, Vivian Cai, Tianxi Hoffnagle, Alison G. Dai, Yael Block, Stefanie Weill, Sydney R. Nadal-Vicens, Mireya Pollastri, Alisha R. Rosenquist, J. Niels Goryachev, Sergey Ongur, Dost Sklar, Pamela Perlis, Roy H. Smoller, Jordan W. CA Int Cohort Collection Bipolar Diso TI Validation of Electronic Health Record Phenotyping of Bipolar Disorder Cases and Controls SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RHEUMATOID-ARTHRITIS; MEDICAL-RECORDS; MAJOR DEPRESSION; LARGE-SCALE; RISK; SCHIZOPHRENIA; RELIABILITY; DISCOVERY; DIAGNOSES; LOCI AB Objective: The study was designed to validate use of electronic health records (EHRs) for diagnosing bipolar disorder and classifying control subjects. Method: EHR data were obtained from a health care system of more than 4.6 million patients spanning more than 20 years. Experienced clinicians reviewed charts to identify text features and coded data consistent or inconsistent with a diagnosis of bipolar disorder. Natural language processing was used to train a diagnostic algorithm with 95% specificity for classifying bipolar disorder. Filtered coded data were used to derive three additional classification rules for case subjects and one for control subjects. The positive predictive value (PPV) of EHR-based bipolar disorder and subphenotype diagnoses was calculated against diagnoses from direct semi-structured interviews of 190 patients by trained clinicians blind to EHR diagnosis. Results: The PPV of bipolar disorder defined by natural language processing was 0.85. Coded classification based on strict filtering achieved a value of 0.79, but classifications based on less stringent criteria performed less well. No EHR-classified control subject received a diagnosis of bipolar disorder on the basis of direct interview (PPV=1.0). For most subphenotypes, values exceeded 0.80. The EHR-based classifications were used to accrue 4,500 bipolar disorder cases and 5,000 controls for genetic analyses. Conclusions: Semiautomated mining of EHRs can be used to ascertain bipolar disorder patients and control subjects with high specificity and predictive value compared with diagnostic interviews. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research. C1 [Smoller, Jordan W.] Partners HealthCare Syst, Res Informat Syst & Comp, Boston, MA 02199 USA. Massachusetts Gen Hosp, Comp Sci Lab, Dept Neurol,Ctr Expt Drugs & Diagnost, Dept Psychiat,Ctr Anxiety & Traumat Stress Disord, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Icahn Sch Med Mt Sinai, Div Psychiat Genom, Dept Psychiat, New York, NY 10029 USA. RP Smoller, JW (reprint author), Partners HealthCare Syst, Res Informat Syst & Comp, Boston, MA 02199 USA. EM jsmoller@hms.harvard.edu RI Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; Moran, Jennifer/0000-0002-5664-4716; Minnier, Jessica/0000-0002-3527-2757 FU NIMH [R01 MH-085542, K24 MH-094614, R01 MH-100286] FX Supported by NIMH grant R01 MH-085542 to Drs. Smolter and Sklar. Dr. Smoller is also supported by NIMH grant K24 MH-094614. Dr. Perlis is supported by NIMH grant R01 MH-100286. NR 32 TC 8 Z9 8 U1 1 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2015 VL 172 IS 4 BP 363 EP 372 DI 10.1176/appi.ajp.2014.14030423 PG 10 WC Psychiatry SC Psychiatry GA CE8TS UT WOS:000352117600012 PM 25827034 ER PT J AU Uher, R Ripke, S Muller-Myhsok, B Lewis, CM Perlis, RH AF Uher, Rudolf Ripke, Stephan Mueller-Myhsok, Bertram Lewis, Cathryn M. Perlis, Roy H. TI Association of a Brain Methylation Site With Clinical Outcomes in Depression Does Not Replicate Across Populations SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Uher, Rudolf] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. Broad Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. Max Planck Inst Psychiat, D-80804 Munich, Germany. Munich Cluster Syst Neurol SyNergy, Munich, Germany. RP Uher, R (reprint author), Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. RI Lewis, Cathryn/A-5225-2010 OI Lewis, Cathryn/0000-0002-8249-8476 FU Eli Lilly; Genomind LLC; Healthrageous; Perfect Health; Pfizer; Proteus Biomedical; Psybrain; RID Ventures FX Dr. Muller-Myhsok is a consultant with HMNC and an inventor on several patents in the subject area of pharmacogenetics. Dr. Lewis has received consultant fees from Eli Lilly. Dr. Perlis has served on scientific advisory boards or received consulting fees from Genomind LLC, Healthrageous, Perfect Health, Pfizer, Proteus Biomedical, Psybrain, and RID Ventures, and he receives royalties through Massachusetts General Hospital from Concordant Rater Systems (now UBC). Drs. Uher and Ripke report no financial relationships with commercial interests. NR 3 TC 1 Z9 1 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2015 VL 172 IS 4 BP 395 EP 396 DI 10.1176/appi.ajp.2015.14101348 PG 2 WC Psychiatry SC Psychiatry GA CE8TS UT WOS:000352117600019 PM 25827039 ER PT J AU Carson, SS Fowler, RA Cobb, JP Arabi, YM Ingbar, DH AF Carson, Shannon S. Fowler, Robert A. Cobb, J. Perren Arabi, Yaseen M. Ingbar, David H. CA ATS Taskforce Emerging Pathogens TI Global Participation in Core Data Sets for Emerging Pathogens SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY SYNDROME CORONAVIRUS; CRITICALLY-ILL PATIENTS; EBOLA-VIRUS DISEASE; WEST-AFRICA; INFECTION; OUTCOMES C1 [Carson, Shannon S.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Fowler, Robert A.] Univ Toronto, Toronto, ON, Canada. [Cobb, J. Perren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arabi, Yaseen M.] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Ingbar, David H.] Univ Minnesota, Minneapolis, MN USA. RP Carson, SS (reprint author), Univ N Carolina, Chapel Hill, NC 27515 USA. OI Ingbar, David H./0000-0003-1695-4493 NR 7 TC 3 Z9 3 U1 0 U2 1 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 APR 1 PY 2015 VL 191 IS 7 BP 728 EP 730 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CE8UC UT WOS:000352118600006 PM 25830518 ER PT J AU Hoge, MA Karel, MJ Zeiss, AM Alegria, M Moye, J AF Hoge, Michael A. Karel, Michele J. Zeiss, Antonette M. Alegria, Margarita Moye, Jennifer TI Strengthening Psychology's Workforce for Older Adults Implications of the Institute of Medicine's Report to Congress SO AMERICAN PSYCHOLOGIST LA English DT Article DE older adult; mental health; substance use; geropsychology; workforce development ID MENTAL-HEALTH-CARE; PROFESSIONAL GEROPSYCHOLOGY; CONTINUING-EDUCATION; DEPRESSIVE SYMPTOMS; CONTROLLED-TRIAL; DEMENTIA; INTERVENTIONS; CAREGIVERS; VETERANS; PROGRAM AB Professional psychology faces an urgent crisis, which the following facts paint in stark relief. Adults over age 65 will rise to 20% of the U.S. population over the next 15 years and already account for a third of the country's health care expenditures. Up to 8 million older adults experience mental health and substance use conditions in a given year, yet most psychologists receive no training in their assessment and treatment. No more than an estimated 4%, or 3,000, psychologists nationwide specialize in geropsychology; a ratio approaching 3,000 to 1. A small group of advocates within the profession have sounded the alarm and worked to strengthen geropsychology as a specialty, but this has had very limited impact on the actual supply of psychologists qualified to provide services to this population. In 2012, an Institute of Medicine (IOM) committee released a report on the crisis regarding the mental health and substance use workforce for older adults. Drawing on that report, a team composed of geropsychologists, along with psychologists who served on the IOM committee, identifies in this article priority areas for workforce development. The authors assess the progress of psychology in each of these areas and offer a set of recommendations for future efforts by this profession to develop its own workforce and to strengthen the ability of other caregivers to address the behavioral health needs of older adults. Strengthening its own workforce and responding to the needs of this population is imperative if psychology is to maintain its relevance as a health profession and meet its ethical obligations to an increasingly diverse society. C1 [Hoge, Michael A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Karel, Michele J.; Zeiss, Antonette M.] US Dept Vet Affairs, Mental Hlth Serv, Washington, DC USA. [Alegria, Margarita] Ctr Multicultural Mental Hlth Res, Somerville, MA USA. [Alegria, Margarita] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Moye, Jennifer] VA Boston Healthcare Syst, Boston, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hoge, MA (reprint author), Yale Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA. EM michael.hoge@yale.edu RI Nolasco, Arlette/D-9885-2016; Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Intramural VA [VA999999] NR 60 TC 3 Z9 3 U1 0 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2015 VL 70 IS 3 BP 265 EP 278 DI 10.1037/a0038927 PG 14 WC Psychology, Multidisciplinary SC Psychology GA CF1PJ UT WOS:000352319100004 PM 25844650 ER PT J AU Wiener-Kronish, JP Melo, MFV AF Wiener-Kronish, Jeanine P. Melo, Marcos F. Vidal TI New Investigations of Core Competencies Perioperative Mechanical Ventilation and Assessment of Lung Function SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Wiener-Kronish, Jeanine P.; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. EM mvidalmelo@partners.org FU NHLBI NIH HHS [R01 HL121228] NR 9 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2015 VL 122 IS 4 BP 723 EP 724 DI 10.1097/ALN.0000000000000606 PG 2 WC Anesthesiology SC Anesthesiology GA CF0EX UT WOS:000352216700001 PM 25668412 ER PT J AU Weingart, SD Trueger, NS Wong, N Scofi, J Singh, N Rudolph, SS AF Weingart, Scott D. Trueger, N. Seth Wong, Nelson Scofi, Joseph Singh, Neil Rudolph, Soren S. TI Delayed Sequence Intubation: A Prospective Observational Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY AIRWAY MANAGEMENT; DOUBLE-BLIND; PREOXYGENATION; SEDATION; KETAMINE; VENTILATION; PATIENT; VALUES AB Study objective: We investigate a new technique for the emergency airway management of patients with altered mental status preventing adequate preoxygenation. Methods: This was a prospective, observational, multicenter study of patients whose medical condition led them to impede optimal preintubation preparation because of delirium. A convenience sample of emergency department and ICU patients was enrolled. Patients received a dissociative dose of ketamine, allowing preoxygenation with high-flow nonrebreather mask or noninvasive positive pressure ventilation (NIPPV). After preoxygenation, patients were paralyzed and intubated. The primary outcome of this study was the difference in oxygen saturations after maximal attempts at preoxygenation before delayed sequence intubation compared with saturations just before intubation. Predetermined secondary outcomes and complications were also assessed. Results: A total of 62 patients were enrolled: 19 patients required delayed sequence intubation to allow nonrebreather mask, 39 patients required it to allow NIPPV, and 4 patients required it for nasogastric tube placement. Saturations increased from a mean of 89.9% before delayed sequence intubation to 98.8% afterward, with an increase of 8.9% (95% confidence interval 6.4% to 10.9%). Thirty-two patients were in a predetermined group with high potential for critical desaturation (pre-delayed sequence intubation saturations <= 93%). All of these patients increased their saturations post-delayed sequence intubation; 29 (91%) of these patients increased their post-delayed sequence intubation saturations to greater than 93%. No complications were observed in the patients receiving delayed sequence intubation. Conclusion: Delayed sequence intubation could offer an alternative to rapid sequence intubation in patients requiring emergency airway management who will not tolerate preoxygenation or peri-intubation procedures. It is essentially procedural sedation, with the procedure being preoxygenation. Delayed sequence intubation seems safe and effective for use in emergency airway management. C1 [Weingart, Scott D.] SUNY Stony Brook, Dept Emergency Med, Div Emergency Crit Care, Stony Brook, NY 11794 USA. [Trueger, N. Seth] Univ Chicago, Sect Emergency Med, Chicago, IL 60637 USA. [Wong, Nelson] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Scofi, Joseph] Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. [Singh, Neil] Montefiore Med Ctr, Div Crit Care Med, New York, NY USA. [Rudolph, Soren S.] Copenhagen Univ Hosp, Rigshosp, Ctr Head & Orthopaed, Dept Anaesthesia, Copenhagen, Denmark. RP Weingart, SD (reprint author), SUNY Stony Brook, Dept Emergency Med, Div Emergency Crit Care, Stony Brook, NY 11794 USA. EM scottweingart@gmail.com OI Trueger, N. Seth/0000-0001-8797-2192 NR 17 TC 15 Z9 15 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2015 VL 65 IS 4 BP 349 EP 355 DI 10.1016/j.annemergmed.2014.09.025 PG 7 WC Emergency Medicine SC Emergency Medicine GA CE9RN UT WOS:000352181200003 PM 25447559 ER PT J AU Raol, N Caruso, P Hartnick, CJ AF Raol, Nikhila Caruso, Paul Hartnick, Christopher J. TI Use of Imaging to Evaluate Course of the Carotid Artery in Surgery for Velopharyngeal Insufficiency SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE Furlow palatoplasty; pharyngeal flap; velopharyngeal insufficiency; VPI ID VELOCARDIOFACIAL SYNDROME; PHARYNGEAL FLAP; NEUROFIBROMATOSIS; MANAGEMENT; PHARYNGOPLASTY AB Objective: This study aimed to describe syndromes where preoperative imaging may be essential in determining the course of the carotid arteries before velopharyngeal insufficiency (VPI) surgery and therefore affect surgical planning. Methods: Records of children who underwent surgery for VPI between May 1, 2012, and October 30, 2013, at a tertiary care pediatric otolaryngology center were reviewed. Data collected included age at operation, preoperative and postoperative nasometry values, presence of underlying genetic disorders, and imaging findings. Results: Twenty-five patients underwent 33 surgeries for VPI, with 1 posterior pharyngeal wall augmentation, 6 Furlow palatoplasties, 11 sphincter pharyngoplasties, and 15 pharyngeal flaps. Medialized carotid vasculature was identified in 5 of 25 patients (20%). Seven syndromic patients were identified, with 3 patients having 22q11.2 deletion syndrome. All patients (100%) with 22q11.2 deletion syndrome had medialized carotid arteries. Of the 4 additional syndromic children, 2 (50%) had medial internal carotid arteries, with 1 patient diagnosed with neurofibromatosis 1 and another with Prader-Willi syndrome. Both patients underwent Furlow palatoplasty. Conclusion: Whereas 22q11.2 deletion syndrome is recognized as an entity where a medial carotid is often present, other syndromic children may also demonstrate vascular variability. Although a larger study is needed to confirm an increased prevalence in these patients, clinicians may need a higher degree of suspicion while performing the physical examination. If examination findings are suggestive or the disease process may lend itself to this abnormality, vascular imaging can be considered as part of presurgical planning to help guide surgical technique and prevent complications. C1 [Raol, Nikhila; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Raol, Nikhila; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Caruso, Paul] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-4894 EI 1943-572X J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 2015 VL 124 IS 4 BP 261 EP 265 DI 10.1177/0003489414554943 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA CF3RM UT WOS:000352466200002 PM 25324428 ER PT J AU Serpell, J Sidhu, S Vallance, N Panizza, B Randolph, G AF Serpell, Jonathan Sidhu, Stan Vallance, Neil Panizza, Ben Randolph, Gregory TI Re: Consensus statements in surgery: intra-operative neural monitoring for thyroid surgery SO ANZ JOURNAL OF SURGERY LA English DT Letter ID RECURRENT LARYNGEAL NERVE; INJURY; PREVALENCE C1 [Serpell, Jonathan] Monash Univ, Endocrine Surg Unit, Melbourne, Vic 3004, Australia. [Sidhu, Stan] Univ Sydney, Endocrine Surg Unit, Sydney, NSW 2006, Australia. [Vallance, Neil] Monash Med Ctr, Otolaryngol Head & Neck Surg, Melbourne, Vic, Australia. [Panizza, Ben] Princess Alexandra Hosp, Otolaryngol Head & Neck Surg, Brisbane, Qld 4102, Australia. [Randolph, Gregory] Massachusetts Eye & Ear Infirm, Thyroid & Parathyroid Surg Div, Boston, MA 02114 USA. [Randolph, Gregory] Massachusetts Gen Hosp, Div Surg Oncol & Endocrine Surg, Boston, MA 02114 USA. [Randolph, Gregory] Harvard Univ, Sch Med, Boston, MA USA. RP Serpell, J (reprint author), Monash Univ, Endocrine Surg Unit, Melbourne, Vic 3004, Australia. RI Panizza, Benedict/G-6590-2012 NR 14 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1445-1433 EI 1445-2197 J9 ANZ J SURG JI ANZ J. Surg. PD APR PY 2015 VL 85 IS 4 BP 294 EP 294 DI 10.1111/ans.13068 PG 1 WC Surgery SC Surgery GA CF1DN UT WOS:000352284000030 PM 25828898 ER PT J AU Arnason, T Kamionek, M Yang, M Yantiss, RK Misdraji, J AF Arnason, Thomas Kamionek, Michal Yang, Michelle Yantiss, Rhonda K. Misdraji, Joseph TI Significance of Proximal Margin Involvement in Low-Grade Appendiceal Mucinous Neoplasms SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PSEUDOMYXOMA PERITONEI; RIGHT HEMICOLECTOMY; VERMIFORM APPENDIX AB Context.-Appendiceal adenomas and low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix are cured by appendectomy. However, involvement of the proximal margin raises concern for residual disease. Some patients with a positive margin at appendectomy undergo cecal resection to eliminate a perceived risk for tumor recurrence or dissemination, although that likelihood is assumed rather than demonstrated. Objective.-To determine whether involvement of the proximal appendiceal resection margin by adenoma or LAMN is a risk factor for local development of recurrence or pseudomyxoma peritonei. Design.-Appendiceal adenomas and LAMNs confined to the appendix were considered for the study if they showed neoplasia or dissecting mucin at the proximal margin. The presence or absence of residual tumor in cecal resections was determined. Follow-up data were obtained from clinical records. Results.-Sixteen patients (14 female, 2 male) with LAMN (n = 15) or adenoma (n = 1) and an involved proximal resection margin were identified, including 9 with neoplastic epithelium within the lumen and 7 with acellular mucin in the appendiceal wall at the margin. Six patients underwent cecal resection and the others were nonsurgically followed. No cecal resection had residual neoplasia. No patient developed recurrence or pseudomyxoma peritonei (mean follow-up, 4.7 years). Conclusions.-In patients with LAMNs confined to the appendix, involvement of the appendectomy margin by neoplastic epithelium or acellular mucin does not predict recurrence of disease, even without further surgery. A conservative approach to managing these patients can be justified. C1 [Arnason, Thomas; Kamionek, Michal; Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arnason, Thomas; Kamionek, Michal; Misdraji, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Arnason, Thomas] Queen Elizabeth 2 Hlth Sci Ctr, Div Anat Pathol, Halifax, NS, Canada. [Arnason, Thomas] Dalhousie Univ, Halifax, NS, Canada. [Yang, Michelle] Univ Massachusetts, Dept Pathol, Mem Med Ctr, Worcester, MA 01605 USA. [Yantiss, Rhonda K.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 105,55 Fruit St, Boston, MA 02114 USA. EM jmisdraji@partners.org FU Royal College of Physicians and Surgeons of Canada (Detweiler Traveling Fellowship); Dalhousie University (McLoughlin Scholarship) FX Dr Arnason's fellowship funding was provided through scholarships from the Royal College of Physicians and Surgeons of Canada (Detweiler Traveling Fellowship) and Dalhousie University (McLoughlin Scholarship). NR 12 TC 3 Z9 3 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2015 VL 139 IS 4 BP 518 EP 521 DI 10.5858/arpa.2014-0246-OA PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA CF0HJ UT WOS:000352223600014 PM 24971927 ER PT J AU Patel, R Mikuls, TR Richards, JS Kerr, G Cannon, GW Baker, JF AF Patel, Ruchika Mikuls, Ted R. Richards, John S. Kerr, Gail Cannon, Grant W. Baker, Joshua F. TI Disease Characteristics and Treatment Patterns in Veterans With Rheumatoid Arthritis and Concomitant Hepatitis C Infection SO ARTHRITIS CARE & RESEARCH LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; VIRUS-INFECTION; UNITED-STATES; US VETERANS; MANIFESTATIONS; RECOMMENDATIONS; PREVALENCE; REGISTRY; CRYOGLOBULINEMIA; METHOTREXATE AB ObjectiveTo assess disease characteristics, disease activity, and treatment patterns in rheumatoid arthritis (RA) patients with comorbid hepatitis C virus (HCV) infection. MethodsRA patients with concomitant HCV were identified within the Veterans Affairs Rheumatoid Arthritis Registry. HCV was defined as at least 1 diagnostic code present in medical record databases. Generalized estimating equations in linear regression models compared component and composite measures of disease activity between HCV-positive and HCV-negative patients over the study period, accounting for within-subject correlations. Similar analysis of pharmacy databases evaluated medication use within each group. ResultsNinety-two of 1,706 registry participants (5.1%) were identified with concomitant HCV. At enrollment, HCV-positive patients were younger (mean SD 61.7 +/- 7.1 years versus 67.5 +/- 11.2 years; P < 0.001), more often African American (35% versus 15%; P < 0.001), and smokers (48% versus 26%; P < 0.001). In unadjusted and adjusted analyses incorporating all study visits, patient-reported outcomes (pain, tender joints, and patient global scores) were higher in HCV-positive patients, contributing to higher disease activity scores. There was no difference in physician-reported outcomes (swollen joints or physician global scores). HCV-positive patients had lower C-reactive protein levels ( -0.30 [95% confidence interval (95% CI) -0.53, -0.07], P = 0.01). Over all visits, HCV-positive patients were less likely to receive methotrexate (odds ratio [OR] 0.27 [95% CI 0.17, 0.40], P < 0.001), and more likely to receive prednisone (OR 1.41 [95% CI 1.02, 1.97], P = 0.04) and anti-tumor necrosis factor (anti-TNF) therapies (OR 1.51 [95% CI 1.04, 2.19], P = 0.03). ConclusionRA patients with concomitant HCV have higher disease activity scores, driven primarily by higher patient-reported measures. HCV-positive patients were more likely to be treated with prednisone and anti-TNF therapies and less likely to receive methotrexate compared to HCV-negative patients. C1 [Patel, Ruchika; Baker, Joshua F.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Patel, Ruchika; Baker, Joshua F.] Univ Penn, Philadelphia, PA 19104 USA. [Mikuls, Ted R.] Nebraska Western Iowa VA Med Ctr, Omaha, NE USA. [Richards, John S.; Kerr, Gail] VA Med Ctr, Washington, DC USA. [Kerr, Gail] Georgetown Univ Hosp, Washington, DC 20007 USA. [Kerr, Gail] Howard Univ Hosp, Washington, DC USA. [Cannon, Grant W.] Salt Lake City VA Med Ctr, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. RP Baker, JF (reprint author), Hosp Univ Penn, Dept Med, Div Rheumatol, 8 Penn Tower Bldg,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center; VA Health Services Research and Development Program of the Veterans Health Administration; Abbott Laboratories; Bristol-Myers Squibb; VA Clinical Science Research & Development Career Development Award [IK2 CX000955]; VA Merit Clinical Science Research & Development Career Development Award FX Supported by the Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center. The VA Rheumatoid Arthritis Registry is supported by the VA Health Services Research and Development Program of the Veterans Health Administration and unrestricted research grants from Abbott Laboratories and Bristol-Myers Squibb. Dr. Baker's work was supported by a VA Clinical Science Research & Development Career Development Award (IK2 CX000955). Dr. Mikuls's work was supported by a VA Merit Clinical Science Research & Development Career Development Award. NR 34 TC 1 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD APR PY 2015 VL 67 IS 4 BP 467 EP 474 DI 10.1002/acr.22463 PG 8 WC Rheumatology SC Rheumatology GA CE8RM UT WOS:000352111800003 PM 25187185 ER PT J AU Shi, LL Mullen, MG Freehill, MT Lin, A Warner, JJP Higgins, LD AF Shi, Lewis L. Mullen, Martin G. Freehill, Michael T. Lin, Albert Warner, Jon J. P. Higgins, Laurence D. TI Accuracy of Long Head of the Biceps Subluxation as a Predictor for Subscapularis Tears SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID ROTATOR CUFF; TENDON TEARS; MR ARTHROGRAPHY; IMAGING FINDINGS; INTEGRITY; DIAGNOSIS; INSERTION; SHOULDER; ANTERIOR; LESIONS AB Purpose: The aim of this study is to understand the relation between long head of the biceps tendon (LHBT) subluxation and full-thickness tears of the subscapularis. Methods: Magnetic resonance imaging (MRI) scans of 94 patients undergoing shoulder arthroscopy were evaluated preoperatively for the presence or absence of LHBT subluxation. Intraoperative pathology of the biceps and subscapularis tendons was recorded. The diagnostic accuracy of LHBT subluxation on preoperative MRI in determining full-thickness subscapularis tendon tears was calculated. Results: Of the 94 patients in this study, 26 were diagnosed with LHBT subluxation preoperatively. Of these 26 patients, 9 were confirmed to have full-thickness tears of the subscapularis tendon (Lafosse grade 2 or higher). Of the remaining 68 patients who did not appear to have LHBT subluxation preoperatively, 2 were confirmed to have full-thickness tears of the subscapularis tendon. Thus LHBT subluxation on MRI as a predictor for full-thickness subscapularis tears had a sensitivity of 82%, specificity of 80%, positive predictive value of 35%, and negative predictive value of 97%. LHBT subluxation was directly correlated with the severity of the subscapularis tendon tear (P < .001). Conclusions: The diagnostic value of subluxation of the LHBT, as seen on an axial MRI scan, lies primarily in its negative predictive value. If the LHBT is not subluxated, it is unlikely that a full-thickness tear of the subscapularis tendon is present. Surgeons should be cautious about relying on biceps subluxation as a primary diagnostic tool in predicting subscapularis tears. C1 [Shi, Lewis L.; Mullen, Martin G.] Univ Chicago Hosp, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA. [Freehill, Michael T.] Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Div Sports Med & Shoulder Surg, Winston Salem, NC USA. [Lin, Albert] Univ Pittsburgh, UPMC, Ctr Sports Med, Div Shoulder Surg & Sports Med, Pittsburgh, PA USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. [Higgins, Laurence D.] Brigham & Womens Hosp, Sports Med & Shoulder Serv, Boston, MA 02115 USA. RP Higgins, LD (reprint author), Brigham & Womens Hosp, Dept Orthopaed, 75 Francis St, Boston, MA 02115 USA. EM ldhiggins@partners.org FU Smith Nephew FX The authors report the following potential conflict of interest or source of funding: M.T.F. receives support from Smith & Nephew. NR 25 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD APR PY 2015 VL 31 IS 4 BP 615 EP 619 DI 10.1016/j.arthro.2014.11.034 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CF0KJ UT WOS:000352232400008 PM 25636987 ER PT J AU Liang, KC Traverso, G Lee, HC Ahsen, OO Wang, Z Potsaid, B Giacomelli, M Jayaraman, V Barman, R Cable, A Mashimo, H Langer, R Fujimoto, JG AF Liang, Kaicheng Traverso, Giovanni Lee, Hsiang-Chieh Ahsen, Osman Oguz Wang, Zhao Potsaid, Benjamin Giacomelli, Michael Jayaraman, Vijaysekhar Barman, Ross Cable, Alex Mashimo, Hiroshi Langer, Robert Fujimoto, James G. TI Ultrahigh speed en face OCT capsule for endoscopic imaging SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; IN-VIVO; GASTROINTESTINAL-TRACT; MAGNIFYING ENDOSCOPY; LIGHT-SOURCE; ENDOMICROSCOPY; MICROSCOPY; CATHETER; PROBE AB Depth resolved and en face OCT visualization in vivo may have important clinical applications in endoscopy. We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Crosssectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications. (C) 2015 Optical Society of America C1 [Liang, Kaicheng; Lee, Hsiang-Chieh; Ahsen, Osman Oguz; Wang, Zhao; Potsaid, Benjamin; Giacomelli, Michael; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Liang, Kaicheng; Lee, Hsiang-Chieh; Ahsen, Osman Oguz; Wang, Zhao; Potsaid, Benjamin; Giacomelli, Michael; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Traverso, Giovanni; Barman, Ross; Langer, Robert] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Traverso, Giovanni] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Traverso, Giovanni; Mashimo, Hiroshi] Harvard Univ, Sch Med, Boston, MA USA. [Potsaid, Benjamin; Cable, Alex] Thorlabs Inc, Adv Imaging Grp, Newton, NJ USA. [Jayaraman, Vijaysekhar] Praevium Res Inc, Santa Barbara, CA USA. [Mashimo, Hiroshi] Vet Affairs Boston Healthcare Syst, Boston, MA USA. RP Liang, KC (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM jgfuji@mit.edu RI Wang, Zhao/E-3515-2015; Ahsen, Osman/K-4524-2015 OI Wang, Zhao/0000-0002-3628-5699; Ahsen, Osman/0000-0003-4811-3429 FU National Institutes of Health [R01-EY011289-26, R44-EY022864-01, R01-CA075289-16, R44-CA101067-05, R01-CA178636-02, R37-EB000244-35, T32-DK007191-38-S1]; Air Force Office of Scientific Research (AFOSR) [FA9550-10-1-0063, FA9550-12-1-0499]; Agency for Science, Technology and Research (Singapore) FX This work was supported in part by the National Institutes of Health R01-EY011289-26, R44-EY022864-01, R01-CA075289-16, R44-CA101067-05, R01-CA178636-02, R37-EB000244-35, T32-DK007191-38-S1, and Air Force Office of Scientific Research (AFOSR) contracts FA9550-10-1-0063 and FA9550-12-1-0499. The authors acknowledge Dr. Jennifer Haupt and Morgan Jamiel of the M.I.T. Division of Comparative Medicine for veterinary support, and Aditya Kalluri of Harvard-M.I.T. Health Sciences and Technology for technical assistance. Kaicheng Liang acknowledges support from the Agency for Science, Technology and Research (Singapore). NR 57 TC 5 Z9 5 U1 4 U2 23 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD APR 1 PY 2015 VL 6 IS 4 BP 1146 EP 1163 DI 10.1364/BOE.6.001146 PG 18 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CF0JB UT WOS:000352228400005 PM 25909001 ER PT J AU Beaudette, K Baac, HW Madore, WJ Villiger, M Godbout, N Bouma, BE Boudoux, C AF Beaudette, Kathy Baac, Hyoung Won Madore, Wendy-Julie Villiger, Martin Godbout, Nicolas Bouma, Brett E. Boudoux, Caroline TI Laser tissue coagulation and concurrent optical coherence tomography through a double-clad fiber coupler SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID IN-VIVO; ENDOSCOPY; MICROSCOPY; SYSTEM; CATHETER; OCT AB Double-clad fiber (DCF) is herein used in conjunction with a double-clad fiber coupler (DCFC) to enable simultaneous and co-registered optical coherence tomography (OCT) and laser tissue coagulation. The DCF allows a single channel fiber-optic probe to be shared: i.e. the core propagating the OCT signal while the inner cladding delivers the coagulation laser light. We herein present a novel DCFC designed and built to combine both signals within a DCF (>90% of single-mode transmission; >65% multimode coupling). Potential OCT imaging degradation mechanisms are also investigated and solutions to mitigate them are presented. The combined DCFC-based system was used to induce coagulation of an ex vivo swine esophagus allowing a real-time assessment of thermal dynamic processes. We therefore demonstrate a DCFC-based system combining OCT imaging with laser coagulation through a single fiber, thus enabling both modalities to be performed simultaneously and in a co-registered manner. Such a system enables endoscopic image-guided laser marking of superficial epithelial tissues or laser thermal therapy of epithelial lesions in pathologies such as Barrett's esophagus. (C) 2015 Optical Society of America C1 [Beaudette, Kathy; Madore, Wendy-Julie; Godbout, Nicolas; Boudoux, Caroline] Polytech Montreal, Ctr Opt Photon & Lasers, Dept Engn Phys, Montreal, PQ H3C 3A7, Canada. [Beaudette, Kathy; Baac, Hyoung Won; Villiger, Martin; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Beaudette, Kathy; Baac, Hyoung Won; Villiger, Martin; Bouma, Brett E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baac, Hyoung Won] Sungkyunkwan Univ, Sch Elect & Elect Engn, Suwon, South Korea. [Bouma, Brett E.] Harvard Massachusetts Inst Technol, Program Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Beaudette, K (reprint author), Polytech Montreal, Ctr Opt Photon & Lasers, Dept Engn Phys, Montreal, PQ H3C 3A7, Canada. EM caroline.boudoux@polymtl.ca RI Godbout, Nicolas/A-6397-2012 OI Godbout, Nicolas/0000-0001-9494-1175 FU Natural Sciences and Engineering Research Council of Canada (NSERC); National Institutes of Health [P41 EB015903]; NSERC; Fonds de recherche du Quebec - Nature et Technologies (FRQ-NT) International Training Program FX The authors thank Mikael Leduc for precious laboratory help as well as Etienne De Montigny and Mathias Strupler for fruitful discussions. This work was supported in part by Ideas to Innovation Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and by the National Institutes of Health, grant P41 EB015903. KB and WJM were supported by a NSERC graduate scholarship; KB is additionally supported by the Fonds de recherche du Quebec - Nature et Technologies (FRQ-NT) International Training Program. NR 32 TC 7 Z9 7 U1 2 U2 13 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD APR 1 PY 2015 VL 6 IS 4 BP 1293 EP 1303 DI 10.1364/BOE.6.001293 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CF0JB UT WOS:000352228400017 PM 25909013 ER PT J AU Wang, H Gardecki, JA Ughi, GJ Jacques, PV Hamidi, E Tearney, GJ AF Wang, Hao Gardecki, Joseph A. Ughi, Giovanni J. Jacques, Paulino Vacas Hamidi, Ehsan Tearney, Guillermo J. TI Ex vivo catheter-based imaging of coronary atherosclerosis using multimodality OCT and NIRAF excited at 633 nm SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; INTRINSIC FLUORESCENCE; SPECTROSCOPY; PLAQUES; IMPACT AB While optical coherence tomography (OCT) has been shown to be capable of imaging coronary plaque microstructure, additional chemical/molecular information may be needed in order to determine which lesions are at risk of causing an acute coronary event. In this study, we used a recently developed imaging system and double-clad fiber (DCF) catheter capable of simultaneously acquiring both OCT and red excited near-infrared autofluorescence (NIRAF) images (excitation: 633 nm, emission: 680nm to 900nm). We found that NIRAF is elevated in lesions that contain necrotic core - a feature that is critical for vulnerable plaque diagnosis and that is not readily discriminated by OCT alone. We first utilized a DCF ball lens probe and a bench top setup to acquire en face NIRAF images of aortic plaques ex vivo (n = 20). In addition, we used the OCT-NIRAF system and fully assembled catheters to acquire multimodality images from human coronary arteries (n = 15) prosected from human cadaver hearts (n = 5). Comparison of these images with corresponding histology demonstrated that necrotic core plaques exhibited significantly higher NIRAF intensity than other plaque types. These results suggest that multimodality intracoronary OCT-NIRAF imaging technology may be used in the future to provide improved characterization of coronary artery disease in human patients. (C)2015 Optical Society of America C1 [Wang, Hao; Gardecki, Joseph A.; Ughi, Giovanni J.; Jacques, Paulino Vacas; Hamidi, Ehsan; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wang, Hao; Gardecki, Joseph A.; Ughi, Giovanni J.; Jacques, Paulino Vacas; Hamidi, Ehsan; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wang, Hao] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Wang, H (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM gtearney@partners.org OI Ughi, Giovanni J./0000-0003-3354-0698 FU National Heart, Lung and Blood Institute of the National Institutes of Health [R01HL093717] FX Research reported in this publication was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under award number R01HL093717. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We also would like to acknowledge Nufern Corporation for assisting us with the double-clad fibers used in this project. NR 23 TC 9 Z9 9 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD APR 1 PY 2015 VL 6 IS 4 BP 1363 EP 1375 DI 10.1364/BOE.6.001363 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CF0JB UT WOS:000352228400024 PM 25909020 ER PT J AU Spitzer, TR AF Spitzer, T. R. TI Engraftment syndrome: double-edged sword of hematopoietic cell transplants SO BONE MARROW TRANSPLANTATION LA English DT Review ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; CAPILLARY LEAK SYNDROME; BREAST-CANCER PATIENTS; RISK-FACTORS; SOLUBLE THROMBOMODULIN; DIAGNOSTIC-CRITERIA; PEDIATRIC-PATIENTS; MANIFESTATIONS AB Engraftment syndrome (ES) after hematopoietic cell transplantation (HCT) is increasingly diagnosed. Common features include fever, pulmonary vascular leak, rash and organ dysfunction. Different diagnostic criteria likely account for the wide (7-90%) range of reported incidences. ES typically occurs within 4 days of granulocyte recovery although a recently described seemingly similar syndrome occurs 41 week before granulocyte recovery after umbilical cord blood cell transplants. Although the clinical manifestations of ES may be identical to those of acute GVHD, ES also has been well described in patients without acute GVHD. The data are conflicting as to whether ES is associated with a higher nonrelapse mortality and worse survival after HCT. The pathophysiology of ES is unclear, but endothelial injury and activated granulocytes in the setting of proinflammatory cytokines may be important. ES typically is self-limited, but, like acute GVHD, responds to corticosteroids. Because ES and acute GVHD may have overlapping features and response to therapy, these disease processes may often not be distinct events. Moreover, features of ES may overlap with those of drug-and radiation-induced toxicities and infection. Further research to better characterize the clinical spectrum and etiology of ES and to determine its relationship to GVHD is needed. C1 Massachusetts Gen Hosp, Bone Marrow Transplant Program, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM tspitzer@partners.org NR 48 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2015 VL 50 IS 4 BP 469 EP 475 DI 10.1038/bmt.2014.296 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE9HQ UT WOS:000352155300001 PM 25581406 ER PT J AU O'Toole, JA Ferguson, CM Swaroop, MN Horick, N Skolny, MN Brunelle, CL Miller, CL Jammallo, LS Specht, MC Taghian, AG AF O'Toole, Jean A. Ferguson, Chantal M. Swaroop, Meyha N. Horick, Nora Skolny, Melissa N. Brunelle, Cheryl L. Miller, Cynthia L. Jammallo, Lauren S. Specht, Michelle C. Taghian, Alphonse G. TI The impact of breast cancer-related lymphedema on the ability to perform upper extremity activities of daily living SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Lymphedema; Breast cancer; Function; Perometer; Quality of life ID QUALITY-OF-LIFE; ARM-LYMPHEDEMA; FOLLOW-UP; CONTROLLED-TRIAL; SURVIVORS; SURGERY; LIMB; PREVALENCE; MORBIDITY; EXERCISE AB We sought to assess the association of breast cancer-related lymphedema (BCRL) with the ability to perform upper extremity activities of daily living (ADL) in our patient population. 324 breast cancer patients who had received treatment for unilateral breast cancer at our institution between 2005 and 2014 were prospectively screened for lymphedema. Bilateral arm measurements were performed pre-operatively and during post-operative follow-up using a Perometer. Patients completed an extensive quality of life (QOL) questionnaire at the time of each study assessment. Lymphedema was defined as a relative volume change (RVC) of a parts per thousand yen10% from the patient's pre-operative baseline measurement. Linear regression models were used to evaluate the relationship between post-operative arm function score (as a continuous variable) and RVC, demographic, clinical, and QOL factors. By multivariate analysis, greater fear of lymphedema (p < 0.0001), more pain (p < 0.0001), body mass index > 25 (p = 0.0015), mastectomy (p = 0.0001), and having an axillary node dissection (p = 0.0045) were all associated with lower functional scores. Higher emotional well-being score (p < 0.0001) and adjuvant chemotherapy (p = 0.0005) were associated with higher post-operative functional score. Neither low-level volume changes (5-10 % RVC) nor BCRL (RVC a parts per thousand yen10 %) were associated with ability to perform upper extremity ADL as measured by self-report (p = 0.99, p = 0.79). This prospective study demonstrates that low-level changes in arm volume (RVC 5-10 %) as well as clinically significant BCRL (RVC a parts per thousand yen10 %) did not impact the self-reported ability to use the affected extremity for ADL. These findings may help to inform clinicians and patients on the importance of prospective screening for lymphedema and QOL which enables early detection and intervention. C1 [O'Toole, Jean A.; Brunelle, Cheryl L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Ferguson, Chantal M.; Swaroop, Meyha N.; Skolny, Melissa N.; Miller, Cynthia L.; Jammallo, Lauren S.; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Horick, Nora] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. [Specht, Michelle C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118, P50CA089393]; Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema FX The study described was supported by Award Number R01CA139118 (AGT), Award Number P50CA089393 (AGT) from the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 48 TC 5 Z9 5 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2015 VL 150 IS 2 BP 381 EP 388 DI 10.1007/s10549-015-3325-3 PG 8 WC Oncology SC Oncology GA CE9ZL UT WOS:000352202200014 PM 25749734 ER PT J AU Allard, C Sahyouni, E Menard, J Houde, G Pesant, MH Perron, P Ouellet, A Moutquin, JM Ardilouze, JL Hivert, MF AF Allard, Catherine Sahyouni, Elie Menard, Julie Houde, Ghislaine Pesant, Marie-Helene Perron, Patrice Ouellet, Annie Moutquin, Jean-Marie Ardilouze, Jean-Luc Hivert, Marie-France TI Gestational Diabetes Mellitus Identification Based on Self-Monitoring of Blood Glucose SO CANADIAN JOURNAL OF DIABETES LA English DT Article DE clinical management; gestational diabetes mellitus; home capillary blood glucose monitoring; impaired glucose tolerance; primary care; screening ID PREGNANCY OUTCOMES; TYPE-2; WOMEN AB In Sherbrooke, the gestational diabetes mellitus (GDM) Regional Committee proposed GDM screening during the first trimester for all pregnant women based on a 50 g glucose challenge test (50 g GCT) followed directly by capillary self-monitoring blood glucose (SMBG) at home. We evaluated implementation of committee's recommendations on the clinical trajectory of women receiving prenatal care at our institution. We analyzed data collected systematically by the Blood Sampling in Pregnancy clinic from 2008 to 2011. We evaluated the clinical trajectory of 7710 pregnant women to assess GDM screening/diagnoses and referral rates to the diabetes care centre (DCC) for education and treatment during both the first and second trimesters. The Canadian Diabetes Association glycemic treatment targets in women with GDM were used as diagnosis thresholds and DCC referral decisions: Fasting glucose of 5.3 mmol/L and postprandial 2 h glucose of 6.7 mmol/L. We found that pregnant women were 28.0 +/- 4.8 years old, and their body mass indexes were 24.5 +/- 5.5 kg/m(2). During the first trimester, 47% of women were screened for GDM, mostly (84%) using the 50 g GCT. Following SMBG, 5.7% were referred to the DCC. Only 32% of women with early GDM had >1 GDM risk factor. Thereafter, 67% of normoglycemic women screened during the first trimester were screened again during the second trimester. Among women screened during the second trimester, most screening was done using 50 g GCT, and 8.8% were referred to the DCC following SMBG. Implementation of 50 g GCT testing followed by direct home SMBG was well implemented in our area. The importance of early GDM screening and rescreening during the second trimester still needs to be emphasized. (C) 2015 Canadian Diabetes Association C1 [Allard, Catherine; Sahyouni, Elie; Menard, Julie; Houde, Ghislaine; Pesant, Marie-Helene; Perron, Patrice; Ouellet, Annie; Moutquin, Jean-Marie; Ardilouze, Jean-Luc; Hivert, Marie-France] CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ J1H 5N4, Canada. [Sahyouni, Elie; Houde, Ghislaine; Pesant, Marie-Helene; Perron, Patrice; Ardilouze, Jean-Luc] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Ouellet, Annie; Moutquin, Jean-Marie] Univ Sherbrooke, Dept Obstet & Gynecol, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Harvard Univ, Sch Med, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Harvard Univ, Sch Med, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM marie-france_hivert@harvardpilgrim.org FU Fonds de Recherche du Quebec, Sante; Canadian Institutes for Health Research; CDA; Diabete Quebec; Foundation of Stars; Centre de recherche of the CHUS; University of Sherbrooke FX The BSP clinic and the study were supported by multiple partial fundings, including grants to PP, JLA and MFH (Fonds de Recherche du Quebec, Sante; Canadian Institutes for Health Research; CDA; Diabete Quebec, the Foundation of Stars) as well as institutional funding from the Centre de recherche of the CHUS and the University of Sherbrooke and industry participation by Roche Diagnostics, Abbott, LifeScan, NovoNordisk, Sanofi, Merck, Sun Life Financial and Industrielle Alliance. The authors report no potential conflicts of interest. NR 11 TC 3 Z9 3 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1499-2671 J9 CAN J DIABETES JI Can. J. Diabetes PD APR PY 2015 VL 39 IS 2 BP 162 EP 168 DI 10.1016/j.jcjd.2014.09.002 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF0BP UT WOS:000352207800015 PM 25492558 ER PT J AU Reinherz, EL AF Reinherz, Ellis L. TI alpha beta TCR-Mediated Recognition: Relevance to Tumor-Antigen Discovery and Cancer Immunotherapy SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID T-CELL-RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; THORACIC DUCT LYMPHOCYTES; HEMOLYSIN-FORMING CELLS; T3-MOLECULAR COMPLEX; MONOCLONAL-ANTIBODY; IMMUNE RESPONSE; HIGH-AVIDITY; MHC COMPLEX; CLASS-II AB alpha beta T lymphocytes sense perturbations in host cellular body components induced by infectious pathogens, oncogenic transformation, or chemical or physical damage. Millions to billions of these lymphocytes are generated through T-lineage development in the thymus, each endowed with a clonally restricted surface T-cell receptor (TCR). An individual TCR has the capacity to recognize a distinct "foreign" peptide among the myriad of antigens that the mammalian host must be capable of detecting. TCRs explicitly distinguish foreign from self-peptides bound to major histocompatibility complex (MHC) molecules. This is a daunting challenge, given that the MHC-linked peptidome consists of thousands of distinct peptides with a relevant nonself target antigen often embedded at low number, among orders of magnitude higher frequency self-peptides. In this Masters of Immunology article, I review how TCR structure and attendant mechanobiology involving nonlinear responses affect sensitivity as well as specificity to meet this requirement. Assessment of human tumor-cell display using state-of-the-art mass spectrometry physical detection methods that quantify epitope copy number can help to provide information about requisite T-cell functional avidity affording protection and/or therapeutic immunity. Future rational CD8 cytotoxic T-cell-based vaccines may follow, targeting virally induced cancers, other nonviral immunogenic tumors, and potentially even nonimmunogenic tumors whose peptide display can be purposely altered by MHC-binding drugs to stimulate immune attack. C1 [Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Reinherz, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU SU2C-Farrah Fawcett Foundation Human Papillomavirus (HPV) Translational Cancer Research Team Grant [SU2C-AACR-DT13-14]; NIH [NIH UO1 AI90043] FX E.L. Reinherz was supported by an SU2C-Farrah Fawcett Foundation Human Papillomavirus (HPV) Translational Cancer Research Team Grant (grant number SU2C-AACR-DT13-14) and by the NIH (grant no. NIH UO1 AI90043). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. The Farrah Fawcett Foundation is a 501(c)(3) nonprofit dedicated to cancer research, prevention, and patient support. NR 85 TC 3 Z9 3 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD APR PY 2015 VL 3 IS 4 BP 305 EP U12 DI 10.1158/2326-6066.CIR-15-0042 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA CF2LT UT WOS:000352379500001 PM 25847967 ER PT J AU Jacquemin, G Margiotta, D Kasahara, A Bassoy, EY Walch, M Thiery, J Lieberman, J Martinvalet, D AF Jacquemin, G. Margiotta, D. Kasahara, A. Bassoy, E. Y. Walch, M. Thiery, J. Lieberman, J. Martinvalet, D. TI Granzyme B-induced mitochondrial ROS are required for apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID OXIDOREDUCTASE COMPLEX-I; ELECTRON-TRANSPORT CHAIN; CYTOCHROME-C RELEASE; BOVINE HEART-MITOCHONDRIA; OXYGEN SPECIES PRODUCTION; CELL-DEATH; CASPASE ACTIVATION; PERMEABILITY TRANSITION; SUPEROXIDE-PRODUCTION; ENCODED SUBUNITS AB Caspases and the cytotoxic lymphocyte protease granzyme B (GB) induce reactive oxygen species (ROS) formation, loss of transmembrane potential and mitochondrial outer membrane permeabilization (MOMP). Whether ROS are required for GB-mediated apoptosis and how GB induces ROS is unclear. Here, we found that GB induces cell death in an ROS-dependent manner, independently of caspases and MOMP. GB triggers ROS increase in target cell by directly attacking the mitochondria to cleave NDUFV1, NDUFS1 and NDUFS2 subunits of the NADH: ubiquinone oxidoreductase complex I inside mitochondria. This leads to mitocentric ROS production, loss of complex I and III activity, disorganization of the respiratory chain, impaired mitochondrial respiration and loss of the mitochondrial cristae junctions. Furthermore, we have also found that GB-induced mitocentric ROS are necessary for optimal apoptogenic factor release, rapid DNA fragmentation and lysosomal rupture. Interestingly, scavenging the ROS delays and reduces many of the features of GB-induced death. Consequently, GB-induced ROS significantly promote apoptosis. C1 [Jacquemin, G.; Margiotta, D.; Kasahara, A.; Bassoy, E. Y.; Martinvalet, D.] Univ Geneva, Fac Med, Cell Physiol & Metab, CMU, CH-1211 Geneva, Switzerland. [Walch, M.] Univ Fribourg, Dept Med, Unit Anat, CH-1700 Fribourg, Switzerland. [Thiery, J.] INSERM, U753, Villejuif, France. [Lieberman, J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. RP Martinvalet, D (reprint author), Univ Geneva, Fac Med, Cell Physiol & Metab, CMU, Rue Michel Servet 1, CH-1211 Geneva, Switzerland. EM Denis.Martinvalet@unige.ch FU Ambizione SNSF [PZ00P3_126710/1]; ERC [2010-StG_20091118] FX This work was supported by Ambizione SNSF PZ00P3_126710/1, ERC starting Grant ERC-2010-StG_20091118 and subsides from the Carlos and Elsie de Reuter Foundation and Schmidheiny Foundation. We thank Prof. Krause for NOX1-/- and NOX4-/- embryos (University of Geneva, Geneva, Switzerland) and Olivier Dupont for technical assistance. NR 55 TC 13 Z9 15 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2015 VL 22 IS 5 BP 862 EP 874 DI 10.1038/cdd.2014.180 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CF3XQ UT WOS:000352482800014 PM 25361078 ER PT J AU Minnings, K Kerns, E Fiore, M Fiore, M Parekh, RS DuBois, J Isbell, TS Ferguson, R Fiore, L AF Minnings, Kailey Kerns, Eric Fiore, Melissa Fiore, Madeline Parekh, Rulan S. DuBois, Jeff Isbell, T. Scott Ferguson, Ryan Fiore, Louis TI Chronic kidney disease prevalence in Rivas, Nicaragua: Use of a field device for creatinine measurement SO CLINICAL BIOCHEMISTRY LA English DT Article DE Chronic kidney disease; Creatinine; Point of care testing ID RISK-FACTORS; EL SALVADOR AB Objective: An epidemic of chronic kidney disease (CKD) has been identified in Pacific coastal regions of Central America, and screening in the field in these low income countries remains logistically problematic. We tested the performance characteristics of a point of care creatinine analyzer compared to standardized serum creatinine measurements. Methods: Measurements were conducted in 100 persons from a local health center (n = 34) and hospital (n = 66) in Rivas, Nicaragua using both a point-of-care analyzer (StatSensor Xpress, Nova Biomedical) and serum creatinine by Jaffe kinetic method with a Roche Cobas Integra 400 analyzer. Percent coefficient of variation, sensitivity and specificity of the StatSensor Xpress were determined. Results: The average coefficient of variation (CV) was 1.28% for the serum creatinine and CV for the StatSensor Xpress analyzer was 6.8%. The median intra-individual creatinine results obtained with the StatSensor Xpress device were 0.32 mg/dL higher than those by serum creatinine by Jaffe kinetic method. The sensitivity and specificity of the StatSensor Xpress device for identifying subjects with abnormal creatinine (defined as >1.2 mg/dL) was 100% and 79%, respectively. Conclusions: Point of care testing for creatinine demonstrated acceptable repeatability, excellent sensitivity (100%) and modest specificity (79%). Using the point of care testing will allow for generalized screening in the field in low income countries; however, confirmation for elevated levels >1.2 mg/dL will require a second laboratory test confirmation. (C) 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Minnings, Kailey] Univ Toronto, Fac Med, Toronto, ON M5S 1A8, Canada. [Kerns, Eric] Brown Univ, Warren Alpert Med Sch, Providence, RI 02903 USA. [Fiore, Melissa] Boston VA Healthcare Syst, Boston, MA 02458 USA. [Fiore, Madeline] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Parekh, Rulan S.] Univ Toronto, Univ Hlth Network, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [DuBois, Jeff] Nova Biomed, Waltham, MA 02453 USA. [Isbell, T. Scott] St Louis Univ, Sch Med, St Louis, MO 63104 USA. [Ferguson, Ryan; Fiore, Louis] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Kerns, E (reprint author), Brown Univ, Warren Alpert Med Sch, 222 Richmond St, Providence, RI 02903 USA. EM Kailey.minnings@mail.utoronto.ca; ekerns@lifespan.org; maf333@cornell.edu; lynnefiore@gmail.com; rulan.parekh@sickkids.ca; jadubois@novabio.com; tscott.isbell@gmail.com; rferg@bu.edu; lfiore@bu.edu NR 10 TC 2 Z9 2 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 EI 1873-2933 J9 CLIN BIOCHEM JI Clin. Biochem. PD APR PY 2015 VL 48 IS 6 BP 456 EP 458 DI 10.1016/j.clinbiochem.2015.01.005 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CF4GE UT WOS:000352506000017 PM 25617662 ER PT J AU Gala, MK Chan, AT AF Gala, Manish K. Chan, Andrew T. TI Molecular Pathways: Aspirin andWnt Signaling-A Molecularly Targeted Approach to Cancer Prevention and Treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACTIVATED-RECEPTOR-DELTA; COLORECTAL-CANCER; COLON-CANCER; POLYMORPHISM RS6983267; INTESTINAL POLYPOSIS; SUSCEPTIBILITY LOCUS; RANDOMIZED-TRIALS; CHROMOSOME 8Q24 AB The anti-inflammatory properties of aspirin have resulted in its widespread use as an analgesic, antipyretic, and cardioprotective agent. Beyond these applications, multiple observational studies and randomized controlled trials have demonstrated a chemopreventative role for aspirin, particularly in the development of colorectal neoplasia. Given the criticalimportance of Wnt dysregulation in colorectal carcinogenesis, the interplay between aspirin and canonical Wnt signaling has become a focus of investigation. These studies have illuminated our understanding of the anticancer mechanisms of aspirin, yielding the identification of potential biomarkers for which aspirin's chemopreventative efficacy can be safely optimized into routine clinical practice and providing leads into the discovery of novel preventive and therapeutic targets. In this review, we summarize key experimental and clinical studies of this interaction, as well as highlighting future strategies to advance their clinical translation. (C) 2014 AACR. C1 [Gala, Manish K.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Gala, Manish K.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Gala, MK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 720, Boston, MA 02114 USA. EM mgala@mgh.harvard.edu; achan@mgh.harvard.edu FU Junior Faculty Career Development Award from the American College of Gastroenterology; NIH [K23DK103119, K24DK098311, R01CA137178, R01CA176272, P50CA127003] FX M.K. Gala was supported by a Junior Faculty Career Development Award from the American College of Gastroenterology and the NIH under award number K23DK103119. A.T. Chan was supported by the NIH under award numbers K24DK098311, R01CA137178, R01CA176272, and P50CA127003. NR 57 TC 11 Z9 11 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2015 VL 21 IS 7 BP 1543 EP 1548 DI 10.1158/1078-0432.CCR-14-0877 PG 6 WC Oncology SC Oncology GA CE8FI UT WOS:000352076700008 PM 25501125 ER PT J AU Galloway, TJ Wirth, LJ Colevas, AD Gilbert, J Bauman, JE Saba, NF Raben, D Mehra, R Ma, AW Atoyan, R Wang, J Burtness, B Jimeno, A AF Galloway, Thomas J. Wirth, Lori J. Colevas, Alexander D. Gilbert, Jill Bauman, Julie E. Saba, Nabil F. Raben, David Mehra, Ranee Ma, Anna W. Atoyan, Ruzanna Wang, Jing Burtness, Barbara Jimeno, Antonio TI A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; HISTONE-DEACETYLASE INHIBITORS; HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; EXPRESSION; SURVIVAL; RADIATION; VORINOSTAT; RESISTANCE; CETUXIMAB AB Purpose: CUDC-101 is a small molecule that simultaneously inhibits the epidermal growth factor receptor (EGFR), human growth factor receptor 2 (HER2), and histone deacetylase (HDAC) with preclinical activity in head and neck squamous cell cancer (HNSCC). The primary objective of this investigation is to determine the maximum tolerated dose (MTD) of CUDC-101 with cisplatin-radiotherapy in the treatment of HNSCC. Experimental Design: CUDC-101 monotherapy was administered intravenously three times weekly (Monday, Wednesday, Friday) for a one-week run-in, then continued with concurrent cisplatin (100 mg/m(2) every 3 weeks) and external beam radiation (70 Gy to gross disease) over 7 weeks. Results: Twelve patients with intermediate or high-risk HNSCC enrolled. Eleven were p16INKa (p16)-negative. The MTD of CUDC-101-based combination therapy was established at 275 mg/m(2)/dose. Five patients discontinued CUDC-101 due to an adverse event (AE); only one was considered a dose-limiting toxicity (DLT), at the MTD. Pharmacokinetic evaluation suggested low accumulation with this dosing regimen. HDAC inhibition was demonstrated by pharmacodynamic analyses in peripheral blood mononuclear cells (PBMC), tumor biopsies, and paired skin biopsies. Paired tumor biopsies demonstrated a trend of EGFR inhibition. At 1.5 years of median follow-up, there has been one recurrence and two patient deaths (neither attributed to CUDC-101). The remaining nine patients are free of progression. Conclusions: CUDC-101, cisplatin, and radiation were feasible in intermediate/high-risk patients with HNSCC, with no unexpected patterns of AE. Although the MTD was identified, a high rate of DLT-independent discontinuation of CUDC-101 suggests a need for alternate schedules or routes of administration. (C)2015 AACR. C1 [Galloway, Thomas J.; Mehra, Ranee; Burtness, Barbara] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Colevas, Alexander D.] Stanford Canc Ctr, Stanford, CA USA. [Gilbert, Jill] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Bauman, Julie E.] Univ Pittsburgh, Pittsburgh, PA USA. [Saba, Nabil F.] Emory Univ, Atlanta, GA 30322 USA. [Raben, David; Jimeno, Antonio] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Ma, Anna W.; Atoyan, Ruzanna; Wang, Jing] Curis Inc, Lexington, MA USA. RP Jimeno, A (reprint author), Univ Colorado, Ctr Canc, POB 6511,Mail Stop 8117,12801 East 17th Ave, Aurora, CO 80045 USA. EM barbara.burtness@yale.com; Antonio.Jimeno@ucdenver.edu FU Curis Inc. FX This study was supported by Curis Inc. NR 34 TC 8 Z9 9 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2015 VL 21 IS 7 BP 1566 EP 1573 DI 10.1158/1078-0432.CCR-14-2820 PG 8 WC Oncology SC Oncology GA CE8FI UT WOS:000352076700011 PM 25573383 ER PT J AU Bohanes, P Rankin, CJ Blanke, CD Winder, T Ulrich, CM Smalley, SR Rich, TA Martensen, JA Benson, AB Mayer, RJ Cripps, CM Danenberg, K Makar, KW Zhang, W Benedetti, JK Lenz, HJ AF Bohanes, Pierre Rankin, Cathryn J. Blanke, Charles D. Winder, Thomas Ulrich, Cornelia M. Smalley, Stephen R. Rich, Tyvin A. Martensen, James A. Benson, Al B., III Mayer, Robert J. Cripps, Christine M. Danenberg, Kathleen Makar, Karen W. Zhang, Wu Benedetti, Jacqueline K. Lenz, Heinz-Josef TI Pharmacogenetic Analysis of INT 0144 Trial: Association of Polymorphisms with Survival and Toxicity in Rectal Cancer Patients Treated with 5-FU and Radiation SO CLINICAL CANCER RESEARCH LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; METASTATIC COLORECTAL-CANCER; ANTICANCER DRUG-RESISTANCE; ENDOTHELIAL GROWTH-FACTOR; PHASE-III TRIAL; HUMAN COLON; GSTP1; CHEMORADIOTHERAPY; PROLIFERATION; INTERLEUKIN-8 AB Purpose: We tested whether 18 polymorphisms in 16 genes (GSTP1, COX2, IL10, EGFR, EGF, FGFR4, CCDN1, VEGFR2, VEGF, CXCR2, IL8, MMP3, ICAM1, ERCC1, RAD51, and XRCC3) would predict disease-free survival (DFS), overall survival (OS), and toxicity in the INT0144 trial, which was designed to investigate different postoperative regimens of 5-fluorouracil (5-FU)-based chemoradiation (CRT) in locally advanced rectal cancers: Arm 1 consisted of bolus 5-FU followed by 5-FU protracted venous infusion (PVI) with radiotherapy; arm 2 was induction and concomitant PVI 5-FU with radiotherapy and arm 3 was induction and concomitant bolus 5-FU with radiotherapy. Experimental Design: DNA from 746 stage II/III rectal patients enrolled in the Southwest Oncology Group (SWOG) S9304 phase III trial was analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue. The polymorphisms were analyzed using direct DNA-sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: GSTP1-Ile105Val (rs1695) was significantly associated with DFS and OS and its effect did not vary by treatment arm. The five-year DFS and OS were 53% and 58%, respectively, for G/G, 66% and 72% for G/A, and 57% and 66% for A/A patients. In arm 2, IL8-251A/ A genotype (rs4073) was associated with a lower risk of toxicities (P = 0.04). The VEGFR2 H472Q Q/Q genotype (rs1870377) was associated with a higher risk of grade 3-5 proximal upper gastrointestinal tract (PUGIT) mucositis (P = 0.04) in arm 2. However, in arm 1, this genotype was associated with a lower risk of PUGIT mucositis (P = 0.004). Conclusion: rs1695 may be prognostic in patients with rectal cancer treated with adjuvant CRT. rs4073 and rs1870377 may exhibit different associations with toxicity, according to the 5-FU schedule. (C)2015 AACR. C1 [Bohanes, Pierre; Winder, Thomas; Zhang, Wu; Lenz, Heinz-Josef] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Rankin, Cathryn J.; Benedetti, Jacqueline K.] SWOG Stat Ctr, Seattle, WA USA. [Blanke, Charles D.] Oregon Hlth & Sci Univ, SWOG Grp Chairs Off, Portland, OR 97201 USA. [Ulrich, Cornelia M.] Univ Washington, Seattle, WA 98195 USA. [Ulrich, Cornelia M.; Benedetti, Jacqueline K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Smalley, Stephen R.] Radiol Oncol Ctr Olathe, Olathe, KS USA. [Rich, Tyvin A.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Martensen, James A.] Mayo Clin, Rochester, NY USA. [Benson, Al B., III] Northwestern Univ, Chicago, IL 60611 USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cripps, Christine M.] Ottawa Hosp Canc Ctr, Ottawa, ON, Canada. [Danenberg, Kathleen] Liquid Genom Inc, Torrance, CA USA. RP Lenz, HJ (reprint author), Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Sharon Carpenter Lab, 1441 Eastlake Ave,Suite 3456, Los Angeles, CA 90033 USA. EM lenz@usc.edu FU National Cancer Institute, Department of Health and Human Services (DHHS) [CA32102, CA38926, CA058882, CA142558, CA21115, CA17145, CA25224, CA077202, CA32291, CCSRI021039, CCSRI015469]; NIH [5R01CA105145, P30CA014089]; Ligue Suisse contre le Cancer; Daniel Butler Memorial Research Fund FX This work was supported, in part, by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, Department of Health and Human Services (DHHS): CA32102, CA38926, CA058882, CA142558, CA21115, CA17145 CA25224, CA077202, CA32291, CCSRI021039, and CCSRI015469; and by NIH grants 5R01CA105145 and NIH P30CA014089. P. Bohanes was supported by a research grant from "Ligue Suisse contre le Cancer" and by the Daniel Butler Memorial Research Fund. NR 34 TC 1 Z9 1 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2015 VL 21 IS 7 BP 1583 EP 1590 DI 10.1158/1078-0432.CCR-14-0857 PG 8 WC Oncology SC Oncology GA CE8FI UT WOS:000352076700013 PM 25589620 ER PT J AU Galluzzi, L Pietrocola, F Bravo-San Pedro, JM Amaravadi, RK Baehrecke, EH Cecconi, F Codogno, P Debnath, J Gewirtz, DA Karantza, V Kimmelman, A Kumar, S Levine, B Maiuri, MC Martin, SJ Penninger, J Piacentini, M Rubinsztein, DC Simon, HU Simonsen, A Thorburn, AM Velasco, G Ryan, KM Kroemer, G AF Galluzzi, Lorenzo Pietrocola, Federico Bravo-San Pedro, Jose Manuel Amaravadi, Ravi K. Baehrecke, Eric H. Cecconi, Francesco Codogno, Patrice Debnath, Jayanta Gewirtz, David A. Karantza, Vassiliki Kimmelman, Alec Kumar, Sharad Levine, Beth Maiuri, Maria Chiara Martin, Seamus J. Penninger, Josef Piacentini, Mauro Rubinsztein, David C. Simon, Hans-Uwe Simonsen, Anne Thorburn, Andrew M. Velasco, Guillermo Ryan, Kevin M. Kroemer, Guido TI Autophagy in malignant transformation and cancer progression SO EMBO JOURNAL LA English DT Review DE adaptive stress responses; Beclin 1; inflammation; KRAS; mitophagy ID TUMOR-SUPPRESSOR GENE; STRESS-INDUCED AUTOPHAGY; ADVANCED SOLID TUMORS; ANTICANCER IMMUNE-RESPONSES; HYPOXIA-INDUCED AUTOPHAGY; BECLIN 1 PHOSPHORYLATION; RENAL-CELL CARCINOMA; HUMAN-BREAST-CANCER; HUMAN GLIOMA-CELLS; PHASE-I TRIAL AB Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy. C1 [Galluzzi, Lorenzo; Pietrocola, Federico; Bravo-San Pedro, Jose Manuel; Maiuri, Maria Chiara; Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Pas Ligue Natl Canc 11, Paris, France. [Galluzzi, Lorenzo; Pietrocola, Federico; Bravo-San Pedro, Jose Manuel; Maiuri, Maria Chiara; Kroemer, Guido] INSERM, U1138, Paris, France. [Galluzzi, Lorenzo; Pietrocola, Federico; Bravo-San Pedro, Jose Manuel; Maiuri, Maria Chiara] Gustave Roussy Canc Campus, Villejuif, France. [Galluzzi, Lorenzo; Codogno, Patrice; Kroemer, Guido] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Baehrecke, Eric H.] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA USA. [Cecconi, Francesco] Danish Canc Soc Res Ctr, Cell Stress & Survival Unit, Copenhagen, Denmark. [Cecconi, Francesco] Univ Roma Tor Vergata, IRCCS Fdn Santa Lucia, Rome, Italy. [Cecconi, Francesco; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy. [Codogno, Patrice] INEM, Paris, France. [Codogno, Patrice] INSERM, U1151, Paris, France. [Codogno, Patrice] CNRS, UMR8253, Paris, France. [Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Debnath, Jayanta] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol Toxicol & Med, Richmond, VA USA. [Karantza, Vassiliki] Merck Res Labs, Rahway, NJ USA. [Kimmelman, Alec] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Kumar, Sharad] Univ S Australia, Ctr Canc Biol, Adelaide, SA 5001, Australia. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Ctr Autophagy Res, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Martin, Seamus J.] Trinity Coll Dublin, Smurfit Inst, Dept Genet, Dublin, Ireland. [Penninger, Josef] Austrian Acad Sci, Inst Mol Biotechnol, A-1010 Vienna, Austria. [Piacentini, Mauro] Natl Inst Infect Dis IRCCS Lazzaro Spallanzani, Rome, Italy. [Rubinsztein, David C.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England. [Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland. [Simonsen, Anne] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Thorburn, Andrew M.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA. [Velasco, Guillermo] Univ Complutense Madrid, Sch Biol, Dept Biochem & Mol Biol 1, Madrid, Spain. [Velasco, Guillermo] IdISSC, Madrid, Spain. [Ryan, Kevin M.] Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland. [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France. [Kroemer, Guido] Gustave Roussy Canc Campus, Metabol & Cell Biol Platforms, Villejuif, France. RP Galluzzi, L (reprint author), Ctr Rech Cordeliers, Equipe Labellisee Pas Ligue Natl Canc 11, Paris, France. EM deadoc@vodafone.it RI Bravo San Pedro, Jose Manuel/F-1680-2015; Penninger, Josef/I-6860-2013; Velasco, Guillermo/H-5260-2012; Piacentini, Mauro/I-2411-2016; OI Bravo-San Pedro, Jose Manuel/0000-0002-5781-1133; Kumar, Sharad/0000-0001-7126-9814; Penninger, Josef/0000-0002-8194-3777; Velasco, Guillermo/0000-0002-1994-2386; Piacentini, Mauro/0000-0003-2919-1296; Ryan, Kevin M./0000-0002-1059-9681; Simon, Hans-Uwe/0000-0002-9404-7736; Simonsen, Anne/0000-0003-4711-7057; Cecconi, Francesco/0000-0002-5614-4359 FU Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); European Commission (ArtForce); European Research Council (ERC); LabEx Immuno-Oncology; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI); American Cancer Society [IRG-14-192-40]; National Health and Medical Research Council of Australia [1041807, 1002863]; Ministry of Health of Italy ('Ricerca Corrente'); Ministry of Health of Italy ('Ricerca Finalizzata'); Associazione Italiana per la Ricerca sul Cancro (AIRC); Swiss National Science Foundation; Swiss Cancer League; European Commission (MEL-PLEX); Spanish Ministry of Economy and Competitiveness (MINECO); Fondo Europeo de Desarrollo Regional (FEDER) [PI12/02248, FR2009-0052, IT2009-0053]; Fundacion Mutua Madrilena [AP101042012]; Fundacio La Marato de TV3 [20134031] FX GK is supported by the Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). DG is supported by the American Cancer Society (Institutional Research Grant IRG-14-192-40). SK is supported by the National Health and Medical Research Council of Australia Project Grant (1041807) and a Senior Principal Research Fellowship (1002863). MP is supported by grants from the Ministry of Health of Italy ('Ricerca Corrente' and 'Ricerca Finalizzata') and Associazione Italiana per la Ricerca sul Cancro (AIRC). HUS is supported by the Swiss National Science Foundation, Swiss Cancer League, and the European Commission (MEL-PLEX). GV is supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO), Fondo Europeo de Desarrollo Regional (FEDER) (PI12/02248, FR2009-0052 and IT2009-0053), Fundacion Mutua Madrilena (AP101042012) and Fundacio La Marato de TV3 (20134031). NR 280 TC 172 Z9 174 U1 31 U2 125 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 1 PY 2015 VL 34 IS 7 BP 856 EP 880 DI 10.15252/embj.201490784 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE9ME UT WOS:000352167300006 PM 25712477 ER PT J AU De la Marche, W Noens, I Kuppens, S Spilt, JL Boets, B Steyaert, J AF De la Marche, Wouter Noens, Ilse Kuppens, Sofie Spilt, Jantine L. Boets, Bart Steyaert, Jean TI Measuring quantitative autism traits in families: informant effect or intergenerational transmission? SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Autism spectrum disorders; Intergenerational transmission; Assortative mating; Informant effect; Informant contrast ID SOCIAL RESPONSIVENESS SCALE; BROAD AUTISM; SPECTRUM DISORDERS; GENERAL-POPULATION; PARENTAL RATINGS; PHENOTYPE; COMMUNICATION; CHECKLIST; MULTIPLEX; TWIN AB Autism spectrum disorders (ASD) have a high degree of heritability, but there is still much debate about specific causal genes and pathways. To gain insight into patterns of transmission, research has focused on the relatedness of quantitative autism traits (QAT) between family members, mostly using questionnaires. Yet, different kinds of bias may influence research results. In this paper, we focus on possible informant effects and, taking these into account, on possible intergenerational transmission of QAT. This study used multiple informant data retrieved via the Social Responsiveness Scale from 170 families with at least one member with ASD. Using intraclass correlations (ICCs) and mixed model analyses, we investigated inter-informant agreement and differences between parent and teacher reports on children and between self- and other-reports on adults. Using structural equation modelling (SEM), we investigated the relatedness of QAT between family members in ASD families. Parent-teacher agreement about social responsiveness was poor, especially for children with ASD, though agreement between parents was moderate to strong for affected and unaffected children. Agreement between self- and other-report in adult men was good, but only moderate in women. Agreement did not differ between adults with and without ASD. While accounting for informant effects, our SEM results corroborated the assortative mating theory and the intergenerational transmission of QAT from both fathers and mothers to their offspring. C1 [De la Marche, Wouter; Noens, Ilse; Boets, Bart; Steyaert, Jean] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [De la Marche, Wouter] Publ Psychiat Care Ctr Geel, Youth Dept, B-2440 Geel, Belgium. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Kuppens, Sofie] Katholieke Univ Leuven, HIVA Res Inst Work & Soc, Leuven, Belgium. [Spilt, Jantine L.] Katholieke Univ Leuven, Sch Psychol & Child, Leuven, Belgium. [Spilt, Jantine L.] Katholieke Univ Leuven, Adolescent Dev Res Unit, Leuven, Belgium. [Boets, Bart; Steyaert, Jean] Katholieke Univ Leuven, UPC, Child & Adolescent Psychiat Dept, B-3000 Louvain, Belgium. [Steyaert, Jean] Maastricht Univ Hosp, Clin Genet, Maastricht, Netherlands. RP De la Marche, W (reprint author), Publ Psychiat Care Ctr Geel, Youth Dept, Dr Sanodreef 4, B-2440 Geel, Belgium. EM wouter.delamarche@opzgeel.be; jean.steyaert@uz.kuleuven.be FU research foundation flanders, FWO [G.0609.07]; research council of the KU Leuven [IDO/08/013] FX This research was supported by the research foundation flanders, FWO (Grant Number G.0609.07 to JS; BB is postdoctoral fellow of the FWO) and by a grant from the research council of the KU Leuven (IDO/08/013). NR 53 TC 3 Z9 3 U1 3 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 EI 1435-165X J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD APR PY 2015 VL 24 IS 4 BP 385 EP 395 DI 10.1007/s00787-014-0586-z PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CF0JY UT WOS:000352231200003 PM 25086652 ER PT J AU Larose, TL Langhammer, A Chen, Y Camargo, CA Romundstad, P Mai, XM AF Larose, Tricia L. Langhammer, Arnulf Chen, Yue Camargo, Carlos A., Jr. Romundstad, Pal Mai, Xiao-Mei TI Serum 25-hydroxyvitamin D levels and lung function in adults with asthma: the HUNT Study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID VITAMIN-D DEFICIENCY; PULMONARY-FUNCTION; ASSOCIATION; CHILDREN; HEALTH; DISEASE; COHORT; ATOPY AB The association between vitamin D status and lung function in adults with asthma remains unclear. We studied this cross-sectional association and possible modification by sex and allergic rhinitis in 760 adults (aged 19-55 years) with self-reported asthma in the Nord-Trondelag Health Study. Serum 25-hydroxyvitamin D (25(OH) D) level <50 nmol.L-1 was considered deficient. Lung function measurements included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio. Multiple linear regression models were used to estimate adjusted regression coefficients (beta) and 95% confidence intervals. 44% of asthma adults had serum 25(OH) D levels <50 nmol.L-1. Its associations with lung function measures seemed to be modified by sex and allergic rhinitis (p<0.03 for three-way interaction term). Overall, a serum 25(OH) D level <50 nmol.L-1 was not associated with lung function measurements in subjects with allergic rhinitis in this asthma cohort. In men with asthma but without allergic rhinitis, however, a serum 25(OH) D level <50 nmol.L-1 was significantly associated with lower FEV1/FVC ratio (beta=-8.60%; 95% CI: -16.95%--0.25%). Low serum 25(OH) D level was not associated with airway obstruction in most asthma adults with the exception of men with asthma but without allergic rhinitis. C1 [Larose, Tricia L.; Langhammer, Arnulf; Romundstad, Pal; Mai, Xiao-Mei] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7491 Trondheim, Norway. [Chen, Yue] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1N 6N5, Canada. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Larose, TL (reprint author), Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7491 Trondheim, Norway. EM tricia.larose@ntnu.no OI Romundstad, Pal Richard/0000-0003-2061-4336 FU Research Council of Norway [201895/V50]; ExtraStiftelsen Helse og Rehabilitering and Landsforeningen for hjerte-og lungesyke [2011.2.0215]; Liason Committee Central Norway Regional Health Authority - NTNU FX This study was supported by the Research Council of Norway (project 201895/V50), ExtraStiftelsen Helse og Rehabilitering and Landsforeningen for hjerte-og lungesyke (project 2011.2.0215), and Liason Committee Central Norway Regional Health Authority - NTNU. NR 31 TC 5 Z9 5 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD APR PY 2015 VL 45 IS 4 BP 1019 EP 1026 DI 10.1183/09031936.00069714 PG 8 WC Respiratory System SC Respiratory System GA CE7MB UT WOS:000352023800014 PM 25395037 ER PT J AU Naik, AD Lawrence, B Kiefer, L Ramos, K Utech, A Masozera, N Rao, R Petersen, NJ Kunik, ME Cully, JA AF Naik, Aanand D. Lawrence, Briana Kiefer, Lea Ramos, Katherine Utech, Anne Masozera, Nicholas Rao, Radha Petersen, Nancy J. Kunik, Mark E. Cully, Jeffrey A. TI Building a primary care/research partnership: lessons learned from a telehealth intervention for diabetes and depression SO FAMILY PRACTICE LA English DT Article DE Community-based partnership; formative evaluation; implementation; medical home; primary care ID PARTICIPATORY RESEARCH; IMPLEMENTATION-RESEARCH; PARIHS FRAMEWORK; HEALTH AB Introduction. Evidence-based interventions are often poorly translated into primary care settings due to inadequate integration into organizational cultures and clinical workflows. Study designs that blend evaluation of effectiveness and implementation may enhance uptake of interventions into primary care settings. Community-Based Participatory Research (CBPR) models are useful for developing partnerships between research teams and primary care clinical partners to test blended study designs. Methods. We conducted a formative evaluation of partnership building between a health services research team and a primary care community in US Veterans Affairs Health System to conduct a randomized effectiveness trial of an intervention embedded in routine primary care. The formative evaluation used qualitative data drawn from research/clinical partnership meetings. Data were coded and analysed using qualitative framework analysis. Results. The CBPR model guided development of a research/clinical partnership based on a facilitation team consisting of 'external facilitators' (research team), 'internal facilitators' (primary care leadership) and a ` clinical advisory committee' drawn from the primary care community. Qualitative themes focused on: how the intervention components ('evidence') aligned with local clinical cultures, barriers and facilitators to acceptance and adoption of the intervention processes within the context of clinical workflows and identified ` facilitators' of intervention uptake and sustainability. Conclusion. A CBPR model can guide the development of research/clinical partnerships. Partnerships can identify barriers and craft modifications to intervention procedures that promote integration and into primary care workflows. Formative research/ clinical partnerships are critical for designing and testing interventions focused on implementation and sustainability of new evidence within routine primary care. C1 [Naik, Aanand D.; Lawrence, Briana; Kiefer, Lea; Ramos, Katherine; Petersen, Nancy J.; Kunik, Mark E.; Cully, Jeffrey A.] Michael E DeBakey VA Med Ctr, VA HSR&D Houston Ctr Innovat, Houston, TX USA. [Naik, Aanand D.; Lawrence, Briana; Kiefer, Lea; Ramos, Katherine; Utech, Anne; Petersen, Nancy J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Naik, Aanand D.] Univ Texas Houston, Sch Publ Hlth, Dept Hlth Promot & Behav Sci, Houston, TX USA. [Lawrence, Briana] Univ Texas Houston, Sch Publ Hlth, Susan G Komen Canc Dispar Trainee, Houston, TX USA. [Ramos, Katherine] Univ Houston, Dept Counseling Psychol, Houston, TX USA. [Utech, Anne; Masozera, Nicholas; Rao, Radha] Michael E DeBakey VA Med Ctr, Primary Care Line, Houston, TX USA. [Kunik, Mark E.; Cully, Jeffrey A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kunik, Mark E.; Cully, Jeffrey A.] Educ & Clin Ctr, VA South Cent Mental Illness Res, Houston, TX USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, 2450 Holcombe Blvd,Suite 01Y, Houston, TX 77021 USA. EM anaik@bcm.edu OI Ramos, Katherine/0000-0002-7584-3040 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service project [10-135]; Houston Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center [CIN 13-413] FX Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service project (10-135, Naik and Cully, MPIs). Houston Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413) at the Michael E. DeBakey VA Medical Center. NR 19 TC 1 Z9 1 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 EI 1460-2229 J9 FAM PRACT JI Fam. Pr. PD APR PY 2015 VL 32 IS 2 BP 216 EP 223 DI 10.1093/fampra/cmu084 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CF0AH UT WOS:000352204400015 PM 25552674 ER PT J AU Bastu, E Mutlu, MF Yasa, C Dural, O Aytan, AN Celik, C Buyru, F Yeh, J AF Bastu, Ercan Mutlu, Mehmet F. Yasa, Cenk Dural, Ozlem Aytan, Asli Nehir Celik, Cem Buyru, Faruk Yeh, John TI Role of Mucin 1 and Glycodelin A in recurrent implantation failure SO FERTILITY AND STERILITY LA English DT Article DE Glycodelin A; infertility; Mucin 1; recurrent implantation failure ID ENDOMETRIAL PROTEIN PP14; PLACENTAL PROTEIN-14; PREGNANCY LOSS; LUTEAL-PHASE; SERUM LEVELS; EXPRESSION; MISCARRIAGE; WOMEN; RECEPTIVITY; FERTILE AB Objective: To evaluate and compare the levels of Mucin 1 (MUC-1) and Glycodelin A (GdA) in precisely timed endometrial biopsies and blood samples taken from women with recurrent implantation failure, and women with proven fertility, in a control group. Design: Molecular studies in human blood and tissue. Setting: University hospital. Patient(s): Women with recurrent implantation failure and women with proven fertility. Intervention(s): Primary endometrial cells and blood samples during the implantation "window" (between day 7 and day 9 after the surge in luteinizing hormone). Main Outcome Measure(s): Expression of MUC-1 and GdA in the human endometrium and in blood during the implantation window were analyzed by enzyme-linked immunosorbent assay. Additionally, MUC-1 and GdA levels in tissue were analyzed by western blot during the same period. Result(s): Both blood and tissue measurements of MUC-1 and GdA were significantly lower in women with recurrent implantation failure than in fertile women during the implantation window. In addition, we found a highly significant correlation between blood vs. tissue measurements of both MUC-1 and GdA. Conclusion(s): The present study reveals that blood and tissue levels of MUC-1 and GdA are much lower in women with RIF, compared with those in fertile women. Receptivity can be evaluated with noninvasive blood sampling, rather than more-invasive endometrium sampling, as the blood and tissue measurements of MUC-1 and GdA are correlated. (C) 2015 by American Society for Reproductive Medicine. C1 [Bastu, Ercan; Yasa, Cenk; Dural, Ozlem; Aytan, Asli Nehir; Buyru, Faruk] Istanbul Univ, Sch Med, Dept Obstet & Gynecol, Istanbul, Turkey. [Mutlu, Mehmet F.] Hlth Res Syst Womens Hosp, Ankara, Turkey. [Celik, Cem] Bahceci Hlth Grp, Istanbul, Turkey. [Yeh, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Bastu, E (reprint author), Istanbul Univ, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Capa 34093, Istanbul, Turkey. EM ercan.bastu@istanbul.edu.tr OI Bastu, Ercan/0000-0003-0810-6195 NR 33 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2015 VL 103 IS 4 BP 1059 EP U259 DI 10.1016/j.fertnstert.2015.01.025 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CE8QZ UT WOS:000352110400036 PM 25747132 ER PT J AU Consugar, MB Navarro-Gomez, D Place, EM Bujakowska, KM Sousa, ME Fonseca-Kelly, ZD Taub, DG Janessian, M Wang, DY Au, ED Sims, KB Sweetser, DA Fulton, AB Liu, Q Wiggs, JL Gai, XW Pierce, EA AF Consugar, Mark B. Navarro-Gomez, Daniel Place, Emily M. Bujakowska, Kinga M. Sousa, Maria E. Fonseca-Kelly, Zoe D. Taub, Daniel G. Janessian, Maria Wang, Dan Yi Au, Elizabeth D. Sims, Katherine B. Sweetser, David A. Fulton, Anne B. Liu, Qin Wiggs, Janey L. Gai, Xiaowu Pierce, Eric A. TI Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing SO GENETICS IN MEDICINE LA English DT Article DE genetic diagnostic testing; next-generation sequencing; reproducibility; sensitivity; specificity ID LEBERS CONGENITAL AMAUROSIS; RETINITIS-PIGMENTOSA; MITOCHONDRIAL DISEASE; VISUAL IMPAIRMENT; THERAPY; PREVALENCE; MUTATIONS; NUMBER; GENOME; ADULTS AB Purpose: Next-generation sequencing-based methods are being adopted broadly for genetic diagnostic testing, but the performance characteristics of these techniques with regard to test accuracy and reproducibility have not been fully defined. Methods: We developed a targeted enrichment and next-generation sequencing approach for genetic diagnostic testing of patients with inherited eye disorders, including inherited retinal degenerations, optic atrophy, and glaucoma. In preparation for providing this genetic. eye disease (GEDi) test on a CLIA-certified basis, we performed experiments to measure the sensitivity, specificity, and reproducibility, as well as the clinical sensitivity, of the test. Results: The GEDi test is highly reproducible and accurate, with sensitivity and specificity of 97.9 and 100%, respectively, for single-nucleotide variant detection. The sensitivity for variant detection was notably better than the 88.3% achieved by whole-exome sequencing using the same metrics, because of better coverage of targeted genes in the GEDi test as compared with a commercially available exome capture set. Prospective testing of 192 patients with inherited retinal degenerations indicated that the clinical sensitivity of the GEDi test is high, with a diagnostic rate of 51%. Conclusion: Based on quantified performance metrics, the data, suggest that selective targeted enrichment is preferable to whole-exome sequencing for genetic diagnostic testing. C1 [Consugar, Mark B.; Navarro-Gomez, Daniel; Place, Emily M.; Bujakowska, Kinga M.; Sousa, Maria E.; Fonseca-Kelly, Zoe D.; Taub, Daniel G.; Janessian, Maria; Wang, Dan Yi; Au, Elizabeth D.; Liu, Qin; Wiggs, Janey L.; Gai, Xiaowu; Pierce, Eric A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Genom Inst, Boston, MA 02114 USA. [Consugar, Mark B.; Navarro-Gomez, Daniel; Place, Emily M.; Bujakowska, Kinga M.; Sousa, Maria E.; Fonseca-Kelly, Zoe D.; Taub, Daniel G.; Janessian, Maria; Wang, Dan Yi; Au, Elizabeth D.; Liu, Qin; Wiggs, Janey L.; Gai, Xiaowu; Pierce, Eric A.] Harvard Univ, Sch Med, Boston, MA USA. [Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. [Sweetser, David A.] Massachusetts Gen Hosp, Dept Pediat, Div Med Genet, Boston, MA 02114 USA. [Sweetser, David A.] Massachusetts Gen Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02114 USA. [Fulton, Anne B.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA USA. [Pierce, Eric A.] Harvard Univ, Sch Med, Dept Ophthalmol, Berman Gund Lab, Boston, MA USA. [Pierce, Eric A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pierce, EA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Genom Inst, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 FU National Institutes of Health [EY012910, P30EY014104]; March of Dimes; Foundation Fighting Blindness USA FX The authors are grateful to Aliete E. Langsdorf for the technical contribution and to Kendrick Goss for assistance with the PPT1 assays. This work was supported by grants from the National Institutes of Health (EY012910 (E.A.P.) and P30EY014104 (Massachusetts Eye and Ear Infirmary core support)), the March of Dimes (J.L.W.), and the Foundation Fighting Blindness USA (E.A.P. and Q.L.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations or the National Institutes of Health. GEDi sequence data, WES sequence data, and Omni 2.5 SNP data for the four samples used to quantify the performance of the GEDi test are available at dbGAP (study accession no. phs000798.v1.p1). Also, the variants listed in Supplementary Table S7 online have been submitted to the ClinVar database. NR 40 TC 39 Z9 39 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD APR PY 2015 VL 17 IS 4 BP 253 EP 261 DI 10.1038/gim.2014.172 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CF3RT UT WOS:000352466900002 PM 25412400 ER PT J AU Venturini, G Koskiniemi-Kuendig, H Harper, S Berson, EL Rivolta, C AF Venturini, Giulia Koskiniemi-Kuendig, Hanna Harper, Shyana Berson, Eliot L. Rivolta, Carlo TI Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry SO GENETICS IN MEDICINE LA English DT Article DE Ashkenazi; DHDDS; MAK; retinal degeneration; retinitis pigmentosa ID DIPHOSPHATE SYNTHASE GENE; CILIARY LENGTH; USHER-SYNDROME; KINASE MAK; IDENTIFY; DISEASE; CELLS; EYE AB Purpose: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. Methods: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. Results: We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. Conclusion: In contrast to most mutations associated with retinitis pigmentosa which are, in general, extremely rare the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations. Genet Med advance online publication 25 September 2014 C1 [Venturini, Giulia; Koskiniemi-Kuendig, Hanna; Rivolta, Carlo] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Harper, Shyana; Berson, Eliot L.] Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. [Harper, Shyana; Berson, Eliot L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rivolta, C (reprint author), Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. EM carlo.rivolta@unil.ch OI Rivolta, Carlo/0000-0002-0733-9950 FU Swiss National Science Foundation [310030-138346]; Gebert Ruf Foundation, Switzerland; Foundation Fighting Blindness, Columbia, MD FX This work was supported by the Swiss National Science Foundation (grant 310030-138346), the Gebert Ruf Foundation, Switzerland (Rare Diseases-New Technologies grant), and a Center Grant to the Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School (to E.L.B.), from the Foundation Fighting Blindness, Columbia, MD. NR 23 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD APR PY 2015 VL 17 IS 4 BP 285 EP 290 DI 10.1038/gim.2014.132 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CF3RT UT WOS:000352466900006 PM 25255364 ER PT J AU Holmes, LB AF Holmes, Lewis B. TI Hearts and hands as the starting point SO GENETICS IN MEDICINE LA English DT Editorial Material ID MALFORMATIONS C1 MassGen Hosp Children, Med Genet Unit, Boston, MA 02114 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Med Genet Unit, Boston, MA 02114 USA. EM Holmes.Lewis@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD APR PY 2015 VL 17 IS 4 BP 316 EP 318 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA CF3RT UT WOS:000352466900014 PM 25356974 ER PT J AU Chatterjee, NA Singh, JP AF Chatterjee, Neal A. Singh, Jagmeet P. TI Cardiac Resynchronization Therapy: Past, Present, and Future SO HEART FAILURE CLINICS LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Electrical dyssynchrony; Biventricular pacing ID BUNDLE-BRANCH BLOCK; HEART-FAILURE PATIENTS; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; LEFT-VENTRICULAR RESYNCHRONIZATION; INTRAVENTRICULAR-CONDUCTION DELAY; RANDOMIZED-CONTROLLED-TRIALS; ACUTE HEMODYNAMIC-RESPONSE; CLINICAL EVENT REDUCTION; LONG-TERM EFFECTIVENESS; NARROW QRS COMPLEXES AB Cardiac resynchronization therapy (CRT), or biventricular pacing, has become a standard therapeutic modality for patients with symptomatic heart failure (HF), depressed left ventricular (LV) function, and electrical dyssynchrony. Despite the overall success of CRT in improving morbidity and mortality in selected patients with HF, a significant minority demonstrates nonresponse. This review describes the electrical and physiologic rationale for biventricular pacing therapy, summarizes landmark clinical trials assessing CRT efficacy, highlights strategies to optimize the response to CRT, and frames future challenges in the use, delivery, and care of patients undergoing CRT. C1 [Chatterjee, Neal A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Boston, MA 02114 USA. [Singh, Jagmeet P.] Harvard Univ, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp, Cardiol Div,Electrophysiol Lab,Med Sch,Dept Med, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp, Cardiol Div,Electrophysiol Lab,Med Sch,Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM JSINGH@mgh.harvard.edu NR 118 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD APR PY 2015 VL 11 IS 2 BP 287 EP + DI 10.1016/j.hfc.2014.12.007 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE9JP UT WOS:000352160500011 PM 25834976 ER PT J AU Belayev, LY Mor, MK Sevick, MA Shields, AM Rollman, BL Palevsky, PM Arnold, RM Fine, MJ Weisbord, SD AF Belayev, Linda Y. Mor, Maria K. Sevick, Mary Ann Shields, Anne Marie Rollman, Bruce L. Palevsky, Paul M. Arnold, Robert M. Fine, Michael J. Weisbord, Steven D. TI Longitudinal associations of depressive symptoms and pain with quality of life in patients receiving chronic hemodialysis SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Depressive symptoms; depression; quality of life; pain; symptoms ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; PSYCHOSOCIAL FACTORS; DIALYSIS PATIENTS; MANAGEMENT STRATEGIES; MAJOR DEPRESSION; MORTALITY; ADHERENCE; SEVERITY; SURVIVAL AB Depressive symptoms and pain are common in patients on chronic hemodialysis (HD), yet their associations with quality of life (QOL) are not fully understood. We sought to characterize the longitudinal associations of these symptoms with QOL. As part of a trial comparing two symptom management strategies in patients receiving chronic HD, we assessed depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9), and pain using the Short Form McGill Pain Questionnaire (SF-MPQ) monthly over 24 months. We assessed health-related QOL (HR-QOL) quarterly using the Short Form 12 (SF-12) and global QOL (G-QOL) using a single-item survey. We used random effects linear regression to analyze the independent associations of depressive symptoms and pain, scaled based on 5-point increments in symptom scores, with HR-QOL and G-QOL. Overall, 286 patients completed 1417 PHQ-9 and SF-MPQ symptom assessments, 1361 SF-12 assessments, and 1416 G-QOL assessments. Depressive symptoms were independently and inversely associated with SF-12 physical HR-QOL scores (=-1.09; 95% confidence interval [CI]: -1.69, -0.50, P<0.001); SF-12 mental HR-QOL scores (=-4.52; 95% CI: -5.15, -3.89, P<0.001); and G-QOL scores (=-0.64; 95%CI: -0.79, -0.49, P<0.001). Pain was independently and inversely associated with SF-12 physical HR-QOL scores (=-0.99; 95% CI: -1.30, -0.68, P<0.001) and G-QOL scores (=-0.12; 95%CI: -0.20, -0.05, P=0.002); but not with SF-12 mental HR-QOL scores (=-0.16; 95%CI: -0.050, 0.17, P=0.34). In patients receiving chronic HD, depressive symptoms and to a lesser extent pain, are independently associated with reduced HR-QOL and G-QOL. Interventions to alleviate these symptoms could potentially improve patients' HR-QOL and G-QOL. C1 [Belayev, Linda Y.; Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Div Renal Electrolyte, Pittsburgh, PA 15213 USA. [Rollman, Bruce L.; Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Palliat Care, Pittsburgh, PA USA. [Palevsky, Paul M.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, Pittsburgh, PA 15240 USA. [Mor, Maria K.; Shields, Anne Marie; Fine, Michael J.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Health Services Research and Development Merit Review award [IIR 07-190]; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK061296] FX S. D. W. was supported by a Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190) and L. Y. B. was supported by an National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases grant T32 DK061296. NR 54 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1492-7535 EI 1542-4758 J9 HEMODIAL INT JI Hemodial. Int. PD APR PY 2015 VL 19 IS 2 BP 216 EP 224 DI 10.1111/hdi.12247 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CF5FR UT WOS:000352582900002 PM 25403142 ER PT J AU Israeli, M Pollack, MS Shaut, CAE Halpin, A DiPaola, NR Youngs, D Saidman, SL AF Israeli, Moshe Pollack, Marilyn S. Shaut, Carley A. E. Halpin, Anne DiPaola, Nicholas R. Youngs, Danny Saidman, Susan L. TI DIFFERENT STROKES FOR DIFFERENT FOLKS: CONCORDANCE AND DISCORDANCE IN ANTI-HLA ANTIBODY TESTING SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics (ASHI) CY OCT 20-24, 2014 CL Denver, CO SP Amer Soc Histocompatibil & Immunogenet C1 [Israeli, Moshe] Leiden Univ, Med Ctr, Leiden, Netherlands. [Pollack, Marilyn S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shaut, Carley A. E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Halpin, Anne] Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada. [DiPaola, Nicholas R.] Ohio State Univ, Columbus, OH 43210 USA. [Youngs, Danny] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Saidman, Susan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PD APR PY 2015 VL 76 IS 4 MA LBP01 BP 212 EP 212 PG 1 WC Immunology SC Immunology GA CF7PS UT WOS:000352749400005 ER PT J AU Cassidy, B Rae, C Solo, V AF Cassidy, Ben Rae, Caroline Solo, Victor TI Brain Activity: Connectivity, Sparsity, and Mutual Information SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Mutual information; network theory (graphs); time series analysis ID STATE FUNCTIONAL CONNECTIVITY; HUMAN CONNECTOME PROJECT; FMRI CONNECTIVITY; CORTICAL NETWORKS; DEFAULT NETWORK; TIME-SERIES; SELECTION; MODELS; STIMULATION; PROMISE AB We develop a new approach to functional brain connectivity analysis, which deals with four fundamental aspects of connectivity not previously jointly treated. These are: temporal correlation, spurious spatial correlation, sparsity, and network construction using trajectory (as opposed to marginal) Mutual Information. We call the new method Sparse Conditional Trajectory Mutual Information (SCoTMI). We demonstrate SCoTMI on simulated and real fMRI data, showing that SCoTMI gives more accurate and more repeatable detection of network links than competing network estimation methods. C1 [Cassidy, Ben; Solo, Victor] Univ New S Wales, Sch Elect Engn, Sydney, NSW 2052, Australia. [Cassidy, Ben; Rae, Caroline; Solo, Victor] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Rae, Caroline] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Solo, Victor] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Solo, Victor] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Cassidy, B (reprint author), Univ New S Wales, Sch Elect Engn, Sydney, NSW 2052, Australia. EM b.cassidy@neura.edu.au RI Rae, Caroline/B-7537-2008 OI Rae, Caroline/0000-0003-0673-8084 FU NIH Institutes and Centers [1U54MH091657]; McDonnell Center for Systems Neuroscience at Washington University FX The authors would like to thank colleagues at Martinos Center for Biomedical Imaging, within Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA for useful discussions Data were provided [in part] by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: D. Van Essen and K. Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University.. NR 73 TC 2 Z9 2 U1 3 U2 13 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2015 VL 34 IS 4 BP 846 EP 860 DI 10.1109/TMI.2014.2358681 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CF4PU UT WOS:000352533200003 PM 25252277 ER PT J AU Mithal, P Howard, LE Aronson, WJ Kane, CJ Cooperberg, MR Terris, MK Amling, CL Freedland, SJ AF Mithal, Prabhakar Howard, Lauren E. Aronson, William J. Kane, Christopher J. Cooperberg, Matthew R. Terris, Martha K. Amling, Christopher L. Freedland, Stephen J. TI Prostate-specific antigen level, stage or Gleason score: Which is best for predicting outcomes after radical prostatectomy, and does it vary by the outcome being measured? Results from Shared Equal Access Regional Cancer Hospital database SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE disease progression; mortality; prostatectomy; prostatic neoplasms; risk factors ID BIOCHEMICAL RECURRENCE; SEARCH DATABASE; RISK; MORTALITY AB ObjectivesTo assess the ability of preoperative prostate-specific antigen level, Gleason score and stage to predict prostate cancer outcomes beyond biochemical recurrence, specifically castration-resistant prostate cancer, metastases and prostate cancer-specific mortality in radical prostatectomy patients. MethodsWe carried out a retrospective study of 2735 men in the Shared Equal Access Regional Cancer Hospital database treated by radical prostatectomy from 1988 to 2011 with data available on pathological stage, grade and preoperative prostate-specific antigen. We used Cox hazards analyses to examine the predictive accuracy (c-index) of the preoperative prostate-specific antigen (log-transformed), path Gleason score (7, 3+4, 4+3 and 8-10) and path stage grouping (pT2 negative margins; pT2 positive margins; pT3a negative margins; pT3a positive margins; pT3b; vs positive nodes) to predict biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality. ResultsMedian follow up was 8.7years, during which, 937 (34%) had biochemical recurrence, 108 (4%) castration-resistant prostate cancer, 127 (5%) metastases and 68 (2%) prostate cancer-specific mortality. For the outcomes of biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality, the c-indices were, respectively: prostate-specific antigen 0.65, 0.66, 0.64 and 0.69; Gleason score 0.66, 0.83, 0.76 and 0.85; and pathological stage group 0.69, 0.76, 0.72 and 0.80. ConclusionsGleason score can predict with very high accuracy prostate cancer-specific mortality in patients undergoing radical prostatectomy. Thus, Gleason score should be given more weight in nomograms to predict prostate cancer-specific mortality. Furthermore, men with a high Gleason score should be given special consideration for adjuvant treatment or referral to clinical trials because of a higher risk of prostate cancer-specific mortality. (c) 2015 The Japanese Urological Association C1 [Mithal, Prabhakar] Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA. [Howard, Lauren E.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Duke Prostate Ctr,Div Urol Surg, Durham, NC USA. [Howard, Lauren E.; Freedland, Stephen J.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, Durham, NC USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Kane, Christopher J.] Univ Calif San Diego, Med Ctr, Dept Urol, San Diego, CA 92103 USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. [Cooperberg, Matthew R.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA. [Terris, Martha K.] Med Coll Georgia, Dept Surg, Vet Affairs Med Ctr, Urol Sect, Augusta, GA 30912 USA. [Terris, Martha K.] Med Coll Georgia, Dept Surg, Div Urol Surg, Augusta, GA 30912 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Surg, Div Urol, Portland, OR 97201 USA. RP Freedland, SJ (reprint author), Cedars Sinai Med Ctr, 8635 West 3rd,Suite 1070W, Los Angeles, CA 90048 USA. EM stephen.freedland@cshs.org OI Terris, Martha/0000-0002-3843-7270 FU Amgen; Abbott; Dendreon; Astellas FX Matthew R Cooperberg is a paid consultant to Amgen, Abbott, Dendreon, Astellas. NR 9 TC 2 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD APR PY 2015 VL 22 IS 4 BP 362 EP 366 DI 10.1111/iju.12704 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CF0JC UT WOS:000352228500007 PM 25728968 ER PT J AU Liberman, LD Liberman, MC AF Liberman, Leslie D. Liberman, M. Charles TI Dynamics of cochlear synaptopathy after acoustic overexposure SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE auditory nerve; inner ear; synaptic ribbon; glutamate receptor ID INDUCED HEARING-LOSS; AUDITORY-NERVE; HAIR-CELLS; SPIRAL GANGLION; CAT COCHLEA; RIBBON SIZE; FIBERS; INJURY; MOUSE; ORGAN AB Recent work shows that acoustic overexposures causing only transient threshold elevation, and no hair cell loss, nevertheless can cause irreversible loss of the synapses between inner hair cells and cochlear nerve fibers (Kujawa and Liberman 2009). This cochlear synaptopathy, which is selective for the subset of sensory fibers with high thresholds and low spontaneous rates (Furman et al. 2013), appeared fully developed at 24-h post-exposure and showed no recovery by 8 weeks. However, prior studies of this synaptopathy counted only pre-synaptic ribbons, did not examine post-exposure times less than 24 h, and did not analyze the spatial patterns of degeneration around the hair cell circumference. Here, we immunostained for pre-synaptic ribbons, post-synaptic terminals and glutamate receptor patches, as well as the hair cell cytoplasm in noise-exposed and control mice to address the dynamics and spatial organization of the synaptopathic process as a function of post-exposure time from 0 h to 2 weeks. Our analysis showed that the loss of synaptic elements is nearly complete immediately after the 2-h exposure, that there is a reversible downregulation of gluR expression in the peripheral terminals which may be part of a protective mechanism, that there may be reversible reorganization of synaptic locations immediately after exposure, and that the spatial patterns are consistent with the idea that low-SR fibers are mainly found on the modiolar face of the hair cell and are the most vulnerable to noise-induced degeneration. C1 [Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, Leslie D.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM charles_liberman@meei.harvard.edu FU NIDCD [R01 DC 0188, P30 DC 05209] FX This research was supported by grants from the NIDCD: R01 DC 0188 and P30 DC 05209. NR 31 TC 29 Z9 29 U1 5 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD APR PY 2015 VL 16 IS 2 BP 205 EP 219 DI 10.1007/s10162-015-0510-3 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CE9YL UT WOS:000352199500003 PM 25676132 ER PT J AU Liberman, LD Suzuki, J Liberman, MC AF Liberman, Leslie D. Suzuki, Jun Liberman, M. Charles TI Dynamics of cochlear synaptopathy after acoustic overexposure (vol 16, pg 205, 2015) SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Correction C1 [Suzuki, Jun; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, Leslie D.; Suzuki, Jun; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM charles_liberman@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000188] NR 1 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD APR PY 2015 VL 16 IS 2 BP 221 EP 221 DI 10.1007/s10162-015-0514-z PG 1 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CE9YL UT WOS:000352199500004 PM 25732849 ER PT J AU Jacobs, RL Andrews, CP Ramirez, DA Rather, CG Harper, N Jimenez, F Martinez, H Manoharan, M Carrillo, A Gerardi, M Esch, RE He, W Ahuja, SK AF Jacobs, Robert L. Andrews, Charles P. Ramirez, Daniel A. Rather, Cynthia G. Harper, Nathan Jimenez, Fabio Martinez, Hernan Manoharan, Muthu Carrillo, Andrew Gerardi, Margit Esch, Robert E. He, Weijing Ahuja, Sunil K. TI Symptom dynamics during repeated serial allergen challenge chamber exposures to house dust mite SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID POLLEN; IGE; IMMUNOTHERAPY; PLACEBO C1 [Jacobs, Robert L.; Andrews, Charles P.; Ramirez, Daniel A.; Rather, Cynthia G.] Biogen Res Chamber, San Antonio, TX 78201 USA. [Harper, Nathan; Jimenez, Fabio; Martinez, Hernan; Manoharan, Muthu; Carrillo, Andrew; Gerardi, Margit; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Harper, Nathan; Jimenez, Fabio; Martinez, Hernan; Manoharan, Muthu; Carrillo, Andrew; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Esch, Robert E.] Greer Labs, Lenoir, NC USA. RP Jacobs, RL (reprint author), Biogen Res Chamber, San Antonio, TX 78201 USA. EM robert.jacobs7025@sbcglobal.net NR 13 TC 5 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2015 VL 135 IS 4 BP 1071 EP 1075 DI 10.1016/j.jaci.2014.09.047 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA CF0MQ UT WOS:000352238600034 PM 25458003 ER PT J AU Cardozo, ER Thomson, AP Karmon, AE Dickinson, KA Wright, DL Sabatini, ME AF Cardozo, Eden R. Thomson, Alexcis P. Karmon, Anatte E. Dickinson, Kristy A. Wright, Diane L. Sabatini, Mary E. TI Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Cancer; In-vitro fertilization; Fertility preservation ID LOW-DOSE ASPIRIN; QUALITY-OF-LIFE; OOCYTE VITRIFICATION; COMMITTEE OPINION; PREGNANCY RATES; BREAST-CANCER; WOMEN; HYPERSTIMULATION; REPRODUCTION; MUTATIONS AB To compare the in-vitro fertilization (IVF) outcomes of cancer patients who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to gonadotoxic therapy to those of age and time-matched controls with tubal factor infertility. All cancer patients who underwent embryo/oocyte cryopreservation at our institution from 1997 to 2014 were reviewed. Primary outcomes were total dose of gonadotropins used, number of oocytes retrieved, and number of 2pn embryos obtained. Outcomes were compared to age-matched controls with tubal-factor infertility who underwent a fresh embryo transfer within the same relative time period as the IVF cycle of the cancer patient. Sixty-three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo transfer. One hundred twenty-two age-matched controls underwent IVF cycles with fresh transfer, and 23 returned for frozen embryo transfer. No difference was seen between cancer patients and controls with respect to total ampules of gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in twins (44 vs. 14 %; p = 0.035). Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines. C1 [Cardozo, Eden R.; Thomson, Alexcis P.; Karmon, Anatte E.; Dickinson, Kristy A.; Wright, Diane L.; Sabatini, Mary E.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Cardozo, Eden R.; Thomson, Alexcis P.; Karmon, Anatte E.; Dickinson, Kristy A.; Wright, Diane L.; Sabatini, Mary E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sabatini, ME (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM msabatini@partners.org NR 44 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 EI 1573-7330 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD APR PY 2015 VL 32 IS 4 BP 587 EP 596 DI 10.1007/s10815-015-0428-z PG 10 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA CF0GA UT WOS:000352219900014 PM 25595540 ER PT J AU Kwong, LN Boland, GM Frederick, DT Helms, TL Akid, AT Miller, JP Jiang, S Cooper, ZA Song, XZ Seth, S Kamara, J Protopopov, A Mills, GB Flaherty, KT Wargo, JA Chin, L AF Kwong, Lawrence N. Boland, Genevieve M. Frederick, Dennie T. Helms, Timothy L. Akid, Ahmad T. Miller, John P. Jiang, Shan Cooper, Zachary A. Song, Xingzhi Seth, Sahil Kamara, Jennifer Protopopov, Alexei Mills, Gordon B. Flaherty, Keith T. Wargo, Jennifer A. Chin, Lynda TI Co-clinical assessment identifies patterns of BRAF inhibitor resistance in melanoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID METASTATIC MELANOMA; ACQUIRED-RESISTANCE; MEK INHIBITION; BREAST-CANCER; RAF INHIBITION; DABRAFENIB; PATIENT; NRAS; SURVIVAL; MUTATION AB Multiple mechanisms have been described that confer BRAF inhibitor resistance to melanomas, yet the basis of this resistance remains undefined in a sizable portion of patient samples. Here, we characterized samples from a set of patients with melanoma that included individuals at baseline diagnosis, on BRAF inhibitor treatment, and with resistant tumors at both the protein and RNA levels. Using RNA and DNA sequencing, we identified known resistance-conferring mutations in 50% (6 of 12) of the resistant samples. In parallel, targeted proteomic analysis by protein array categorized the resistant samples into 3 stable groups, 2 of which were characterized by reactivation of MAPK signaling to different levels and 1 that was MAPK independent. The molecular relevance of these classifications identified in patients was supported by both mutation data and the similarity of resistance patterns that emerged during a co-clinical trial in a genetically engineered mouse (GEM) model of melanoma that recapitulates the development of BRAF inhibitor resistance. Additionally, we defined candidate biomarkers in pre- and early-treatment patient samples that have potential for predicting clinical responses. On the basis of these observations, we suggest that BRAF inhibitor-resistant melanomas can be actionably classified using protein expression patterns, even without identification of the underlying genetic alteration. C1 [Kwong, Lawrence N.; Helms, Timothy L.; Akid, Ahmad T.; Miller, John P.; Jiang, Shan; Kamara, Jennifer; Wargo, Jennifer A.; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Boland, Genevieve M.; Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Frederick, Dennie T.; Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [Song, Xingzhi; Seth, Sahil; Protopopov, Alexei; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RP Chin, L (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 0091, Houston, TX 77030 USA. EM jwargo@mdanderson.org; lchin@mdanderson.org OI Seth, Sahil/0000-0003-4579-3959; Cooper, Zachary/0000-0003-1059-0940 FU American Cancer Society Postdoctoral Fellowship [117842-PF-09-261-01-TBG]; National Cancer Institute (NCI) [T32 CA009599]; Adelson Medical Research Foundation; NCI [U01 CA168394]; Cancer Prevention Research Institute of Texas [R1204]; NCI Cancer Center Support Grant (CCSG) [P30 CA016672]; NIH [1K08CA160692-01A1, P01CA163222-02, U54CA163125] FX We wish to thank Mike Davies for discussion of the data; Shan Zhou for animal husbandry; Edward Chang for assistance with slide imaging; Alexander Lazar for assistance with pathology; and Yiling Lu for technical assistance with RPPA. L.N. Kwong was supported by an American Cancer Society Postdoctoral Fellowship (117842-PF-09-261-01-TBG). G.M. Boland was supported by the National Cancer Institute (NCI) (T32 CA009599). G.B. Mills and K.T. Flaherty were supported by The Adelson Medical Research Foundation. G.B. Mills and L. Chin were supported by NCI grant U01 CA168394. L. Chin is a CPRIT Scholar in Cancer Research and is supported by funding from the Cancer Prevention Research Institute of Texas (R1204). RPPA was supported by an NCI Cancer Center Support Grant (CCSG) (P30 CA016672). J.A. Wargo was supported by NIH grant 1K08CA160692-01A1; L. Chin was supported by NIH grant P01CA163222-02; and J.A. Wargo and L. Chin were supported by NIH grant U54CA163125. NR 50 TC 16 Z9 16 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2015 VL 125 IS 4 BP 1459 EP 1470 DI 10.1172/JCI78954 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CF0QF UT WOS:000352248600013 PM 25705882 ER PT J AU Xie, J Kim, H Moreau, LA Puhalla, S Garber, J Al Abo, M Takeda, S D'Andrea, AD AF Xie, Jenny Kim, Hyungjin Moreau, Lisa A. Puhalla, Shannon Garber, Judy Al Abo, Muthana Takeda, Shunichi D'Andrea, Alan D. TI RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DNA-DAMAGE RESPONSE; CROSS-LINK REPAIR; COMPLEMENTATION GROUP-A; CORE-COMPLEX PROTEIN; DOUBLE-STRAND BREAKS; UBIQUITIN E3 LIGASE; GENOTOXIC STRESS; GENOME STABILITY; BINDING-PROTEIN; SUMO AB The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is required for excision of DNA interstrand cross-links. The 17 known FA proteins, along with several FA-associated proteins (FAAPs), cooperate in this pathway to detect, unhook, and excise DNA cross-links and to subsequently repair the double-strand breaks generated in the process. In the current study, we identified a patient with FA with a point mutation in FANCA, which encodes a mutant FANCA protein (FANCA(1939S)). FANCA(1939S) failed to bind to the FAAP20 subunit of the FA core complex, leading to decreased stability. Loss of FAAP20 binding exposed a SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO-conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4-mediated (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA. Mutation of the SUMOylation site of FANCA rescued the expression of the mutant protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated polyubiquitination, and degradation, suggesting that regulated release of FAAP20 from FANCA is a critical step in the normal FA pathway. Consistent with this model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivity, and the gene encoding RNF4 was epistatic with the other genes encoding members of the FA/BRCA pathway. Together, the results from our study underscore the importance of analyzing unique patient-derived mutations for dissecting complex DNA repair processes. C1 [Xie, Jenny; Kim, Hyungjin; Moreau, Lisa A.; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Puhalla, Shannon] Univ Pittsburgh, Sch Med, Dept Med Oncol, Pittsburgh, PA USA. [Garber, Judy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Al Abo, Muthana; Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Kyoto, Japan. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Mayer 640,450 Brookline Ave, Boston, MA 02215 USA. EM Alan_dandrea@dfci.harvard.edu FU NIH [5R01DK43889, 4R37HL052725, 5P01HL048546, 5T32CA09361]; DOD [BM110181]; NIH T32 postdoctoral trainee grant; Leukemia and Lymphoma Society career developmental fellowship; Fanconi Anemia Research Fund FX We thank the members of the D'Andrea laboratory for helpful discussions and Ronald Hay (University of Dundee, Dundee, United Kingdom) for providing us with anti-RNF4 antibody. This work was supported by NIH grants 5R01DK43889, 4R37HL052725, 5P01HL048546, and 5T32CA09361; DOD BM110181; NIH T32 postdoctoral trainee grant (to J. Xie); Leukemia and Lymphoma Society career developmental fellowship (to H. Kim); and a grant from the Fanconi Anemia Research Fund. NR 52 TC 9 Z9 9 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2015 VL 125 IS 4 BP 1523 EP 1532 DI 10.1172/JCI79325 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CF0QF UT WOS:000352248600018 PM 25751062 ER PT J AU Sankaran, VG Ulirsch, JC Tchaikovskii, V Ludwig, LS Wakabayashi, A Kadirvel, S Lindsley, RC Bejar, R Shi, JH Lovitch, SB Bishop, DF Steensma, DP AF Sankaran, Vijay G. Ulirsch, Jacob C. Tchaikovskii, Vassili Ludwig, Leif S. Wakabayashi, Aoi Kadirvel, Senkottuvelan Lindsley, R. Coleman Bejar, Rafael Shi, Jiahai Lovitch, Scott B. Bishop, David F. Steensma, David P. TI X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHROMOSOME-INACTIVATION PATTERNS; SIDEROBLASTIC ANEMIA; 5-AMINOLEVULINATE SYNTHASE; IRON; IDENTIFICATION; GENE; HEMATOLOGY AB Macrocytic anemia with abnormal erythropoiesis is a common feature of megaloblastic anemias, congenital dyserythropoietic anemias, and myelodysplastic syndromes. Here, we characterized a family with multiple female individuals who have macrocytic anemia. The proband was noted to have dyserythropoiesis and iron overload. After an extensive diagnostic evaluation that did not provide insight into the cause of the disease, whole-exome sequencing of multiple family members revealed the presence of a mutation in the X chromosomal gene ALAS2, which encodes 5'-aminolevulinate synthase 2, in the affected females. We determined that this mutation (Y365C) impairs binding of the essential cofactor pyridoxal 5'-phosphate to ALAS2, resulting in destabilization of the enzyme and consequent loss of function. X inactivation was not highly skewed in wbc from the affected individuals. In contrast, and consistent with the severity of the ALAS2 mutation, there was a complete skewing toward expression of the WT allele in mRNA from reticulocytes that could be recapitulated in primary erythroid cultures. Together, the results of the X inactivation and mRNA studies illustrate how this X-linked dominant mutation in ALAS2 can perturb normal erythropoiesis through cell-nonautonomous effects. Moreover, our findings highlight the value of whole-exome sequencing in diagnostically challenging cases for the identification of disease etiology and extension of the known phenotypic spectrum of disease. C1 [Sankaran, Vijay G.; Ulirsch, Jacob C.; Ludwig, Leif S.; Wakabayashi, Aoi] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.; Ulirsch, Jacob C.; Ludwig, Leif S.; Wakabayashi, Aoi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.; Ulirsch, Jacob C.; Ludwig, Leif S.; Wakabayashi, Aoi] Broad Inst MIT & Harvard, Cambridge, MA USA. [Tchaikovskii, Vassili; Kadirvel, Senkottuvelan; Bishop, David F.] Mt Sinai Med Ctr, Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Ludwig, Leif S.] Free Univ Berlin, Inst Chem & Biochem, Berlin, Germany. [Ludwig, Leif S.] Charite, D-13353 Berlin, Germany. [Lindsley, R. Coleman; Bejar, Rafael; Steensma, David P.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Lindsley, R. Coleman; Bejar, Rafael; Lovitch, Scott B.; Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Shi, Jiahai] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lovitch, Scott B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, 3 Blackfan Circle,CLS 03001, Boston, MA 02115 USA. EM sankaran@broadinstitute.org; David_Steensma@dfci.harvard.edu RI shi, jiahai/D-7650-2013; OI shi, jiahai/0000-0002-6467-8289; Lovitch, Scott/0000-0001-9013-0105; Ludwig, Leif/0000-0002-2916-2164 FU NIH [R21.HL120791, R01 DK103794]; Edward P. Evans Foundation FX We are grateful to the family for their interest in this study. We thank D. Nathan, S. Lux, C. Brugnara, F. Briccetti, M. Westerman, J. Hirschhorn, G. Evrony, R. Do, D. Bennett, and M. Burns for their valuable advice and support. This work was supported by NIH grants R21.HL120791 and R01 DK103794 (to V.G. Sankaran) and by a grant from the Edward P. Evans Foundation (to D.P. Steensma). NR 23 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2015 VL 125 IS 4 BP 1665 EP 1669 DI 10.1172/JCI78619 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CF0QF UT WOS:000352248600029 PM 25705881 ER PT J AU Somers, MJG Paul, E AF Somers, Michael J. G. Paul, Elahna TI Safety Considerations of Mammalian Target of Rapamycin Inhibitors in Tuberous Sclerosis Complex and Renal Transplantation SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review DE angiomyolipoma; everolimus; mTOR inhibition; rapalog; renal transplantation; safety; sirolimus; tuberous sclerosis complex ID GIANT-CELL ASTROCYTOMAS; MTOR INHIBITORS; CALCINEURIN INHIBITORS; SPORADIC LYMPHANGIOLEIOMYOMATOSIS; PHASE-3 TRIAL; FOLLOW-UP; EVEROLIMUS; SIROLIMUS; RECIPIENTS; MANAGEMENT AB Rapamycin-related mTOR inhibitors (rapalogs) possess immunosuppressive and antiproliferative properties. Their mechanism of action makes them attractive therapies for several disease states but also potentiates adverse effects associated with these drugs. The oral mTOR inhibitor everolimus was recently approved for the treatment of tuberous sclerosis complex (TSC)-associated renal angiomyolipoma. As clinical use of rapalogs for the treatment of TSC increases, nephrologists and urologists who treat both children and adults with renal masses, as well as internists and geneticists with an interest in renal disease, should be aware of their safety profiles. This review presents the clinical experience of rapamycin-related mTOR inhibitors in patients with TSC and summarizes their toxicity profiles in renal transplant and TSC populations. Increased usage of rapalogs in a variety of patient populations demands vigilant monitoring of their safety profiles and rigorous differentiation between disease-specific and drug-specific toxicities. C1 [Somers, Michael J. G.] Boston Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. [Somers, Michael J. G.; Paul, Elahna] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Paul, Elahna] Massachusetts Gen Hosp, Herscot Ctr TSC, Boston, MA 02114 USA. [Paul, Elahna] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Somers, MJG (reprint author), Boston Childrens Hosp, Div Nephrol, 300 Longwood Ave,Suite HU319, Boston, MA 02115 USA. EM Michael.Somers@childrens.harvard.edu FU Novartis Pharmaceuticals Corporation FX The editorial assistance was provided by ApotheCom (funded by Novartis Pharmaceuticals Corporation). NR 51 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-2700 EI 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2015 VL 55 IS 4 BP 368 EP 376 DI 10.1002/jcph.428 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE9CC UT WOS:000352140100002 PM 25402866 ER PT J AU Hivert, MF Perng, W Watkins, SM Newgard, CS Kenny, LC Kristal, BS Patti, ME Isganaitis, E DeMeo, DL Oken, E Gillman, MW AF Hivert, M. F. Perng, W. Watkins, S. M. Newgard, C. S. Kenny, L. C. Kristal, B. S. Patti, M. E. Isganaitis, E. DeMeo, D. L. Oken, E. Gillman, M. W. TI Metabolomics in the developmental origins of obesity and its cardiometabolic consequences SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Review DE DOHaD; metabolic profiling; metabolomics; obesity ID TRIMESTER AMNIOTIC-FLUID; ISCHEMIC-HEART-DISEASE; MASS-SPECTROMETRY; HUMAN BLOOD; LIQUID-CHROMATOGRAPHY; MENDELIAN RANDOMIZATION; CARDIOVASCULAR-DISEASE; METABOLICALLY HEALTHY; EXTRACTION PROTOCOL; INSULIN SENSITIVITY AB In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course. Together, these data can ultimately help to elucidate mechanisms that underlie fetal metabolic programming. Finally, we review current gaps in knowledge and identify areas where the field of metabolomics is likely to provide insights into mechanisms linked to DOHaD in human populations. C1 [Hivert, M. F.; Perng, W.; Oken, E.; Gillman, M. W.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA 02215 USA. [Hivert, M. F.; Perng, W.; Oken, E.; Gillman, M. W.] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Hivert, M. F.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Watkins, S. M.] Metabolon Inc, West Sacramento, CA USA. [Newgard, C. S.] Duke Univ Med, Nutr & Metab Ctr, Durham, NC USA. [Kenny, L. C.] Univ Coll Cork, Irish Ctr Fetal & Neonatal Translat Res, Cork, Ireland. [Kristal, B. S.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kristal, B. S.] Harvard Univ, Sch Med, Boston, MA USA. [Patti, M. E.; Isganaitis, E.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [DeMeo, D. L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [DeMeo, D. L.] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. [Oken, E.; Gillman, M. W.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. RP Perng, W (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,3rd Floor, Boston, MA 02215 USA. EM wei.perng@gmail.com RI Kenny, Louise/G-1112-2011 OI Kenny, Louise/0000-0002-9011-759X FU National Institutes of Health [K24 HD069408]; Thomas O. Pyle Fellowship Fund, Harvard Pilgrim Health Care Institute; US NIH [R37 HD 034568] FX EO and WP were supported by the National Institutes of Health (K24 HD069408). WP was additionally supported by the Thomas O. Pyle Fellowship Fund, Harvard Pilgrim Health Care Institute. Grant: US NIH (R37 HD 034568). NR 112 TC 2 Z9 2 U1 1 U2 13 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 EI 2040-1752 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD APR PY 2015 VL 6 IS 2 BP 65 EP 78 DI 10.1017/S204017441500001X PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF7LR UT WOS:000352738400002 PM 25631626 ER PT J AU Thethi, TK Bajwa, MA Ghanim, H Jo, C Weir, M Goldfine, AB Umpierrez, G Desouza, C Dandona, P Fang-Hollingsworth, Y Raghavan, V Fonseca, VA AF Thethi, Tina K. Bajwa, Muhammad A. Ghanim, Husam Jo, Chanhee Weir, Monica Goldfine, Allison B. Umpierrez, Guillermo Desouza, Cyrus Dandona, Paresh Fang-Hollingsworth, Ying Raghavan, Vasudevan Fonseca, Vivian A. TI Effect of paricalcitol on endothelial function and inflammation in type 2 diabetes and chronic kidney disease SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetes mellitus; Chronic kidney disease; Paricalcitol; Endothelial dysfunction; Inflammation ID VITAMIN-D; CARDIOVASCULAR-DISEASE; RISK; 25-HYDROXYVITAMIN-D; PROTEINURIA; REACTIVITY; ACTIVATION; MELLITUS; ARTERY AB Aims: Patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) have impaired endothelial function. Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation. We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD. Methods: A double blind, randomized, placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD. Paricalcitol 1 mcg or placebo was administered orally once daily for three months. Brachial artery flow mediated dilatation (FMD), nitroglycerine mediated dilation (NMD), and plasma concentrations of inflammatory cytokines, tumor necrosis factor -alpha and interleukin-6, highly-sensitive C-reactive protein; endothelial surface proteins, intercellular adhesion molecule -1 and monocyte chemo attractant protein-1, and plasma glucose, insulin, free fatty acids, and urinary isoprostane were measured at baseline and end of three months. Results: 27 patients in the paricalcitol group and 28 patients in the control group completed the study, though analysis of FMD at both time points was possible in 23 patients in each group. There was no significant difference in the change in FMD, NMD or the biomarkers examined after paricalcitol or placebo treatment. Conclusions: Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress. The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic, lipid and anti-hypertensive therapies. Published by Elsevier Inc. C1 [Thethi, Tina K.; Fonseca, Vivian A.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA USA. [Thethi, Tina K.; Fonseca, Vivian A.] Southeast Louisiana Vet Hlth Care Syst, New Orleans, LA USA. [Bajwa, Muhammad A.; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ghanim, Husam; Dandona, Paresh] Diabet Endocrinol Ctr Western NY, Buffalo, NY USA. [Jo, Chanhee; Weir, Monica; Fang-Hollingsworth, Ying; Raghavan, Vasudevan] Scott & White Mem Hosp & Clin, Temple, TX USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Umpierrez, Guillermo] Emory Univ, Atlanta, GA 30322 USA. [Desouza, Cyrus] Univ Nebraska, Omaha, NE USA. RP Thethi, TK (reprint author), 1430 Tulane Ave SL-53, New Orleans, LA 70112 USA. EM tthethi@tulane.edu FU Abbott; National Institute of General Medical Sciences of the National Institutes of Health [1-U54-GM104940] FX The study was funded by Abbott who had no role in the conduct of the study or interpretation of results or writing of the paper. Drs. Fonseca and Thethi were supported in part by 1-U54-GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The content is solely the responsibility of the authors and does not necessary represent the official views of the National Institutes of Health. NR 22 TC 5 Z9 5 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD APR PY 2015 VL 29 IS 3 BP 433 EP 437 DI 10.1016/j.jdiacomp.2015.01.004 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CE8TN UT WOS:000352117100020 PM 25633573 ER PT J AU Kinnaman, KA Binder, WD Nadel, ES Brown, DFM AF Kinnaman, Karen A. Binder, William D. Nadel, Eric S. Brown, David F. M. TI PETECHIAE, ANEMIA, AND THROMBOCYTOPENIA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; THROMBOTIC MICROANGIOPATHIES; CLINICAL-OUTCOMES; PLASMA-EXCHANGE; PURPURA; ADAMTS13; DEFICIENCY; RITUXIMAB C1 [Kinnaman, Karen A.; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Kinnaman, Karen A.; Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Binder, William D.] Brown Univ, Sch Med, Dept Emergency Med, Providence, RI 02912 USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 110,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2015 VL 48 IS 4 BP 461 EP 465 PG 5 WC Emergency Medicine SC Emergency Medicine GA CE8RU UT WOS:000352112600016 PM 25661311 ER PT J AU Wilcox, SR Seigel, TA Strout, TD Schneider, JI Mitchell, PM Marcolini, EG Cocchi, MN Smithline, HA Lutfy-Clayton, L Mullen, M Ilgen, JS Richards, JB AF Wilcox, Susan R. Seigel, Todd A. Strout, Tania D. Schneider, Jeffrey I. Mitchell, Patricia M. Marcolini, Evie G. Cocchi, Michael N. Smithline, Howard A. Lutfy-Clayton, Lucienne Mullen, Marie Ilgen, Jonathan S. Richards, Jeremy B. TI EMERGENCY MEDICINE RESIDENTS' KNOWLEDGE OF MECHANICAL VENTILATION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE mechanical ventilation; critical care; education; residents ID TRAUMATIC BRAIN-INJURY; LENGTH-OF-STAY; PRESSURE VENTILATION; INTUBATION; DEPARTMENTS; COMPETENCE; INITIATION; PATIENT; HYPOTENSION; CONFIDENCE AB Background: Although Emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) residency curricula. Objectives: The objective of this study was to quantify EM residents' education, experience, and knowledge regarding mechanical ventilation. Methods: We developed a survey of residents' educational experiences with ventilators and an assessment tool with nine clinical questions. Correlation and regression analyses were performed to evaluate the relationship between residents' scores on the assessment instrument and their training, education, and comfort with ventilation. Results: Of 312 EM residents, 218 responded (69.9%). The overall correct response rate for the assessment tool was 73.3%, standard deviation (SD) +/- 22.3. Seventy-seven percent (n = 167) of respondents reported <= 3 h of mechanical ventilation education in their residency curricula over the past year. Residents reported frequently caring for ventilated patients in the ED, as 64% (n = 139) recalled caring for >= 4 ventilated patients per month. Fifty-three percent (n = 116) of residents endorsed feeling comfortable caring for mechanically ventilated ED patients. In multiregression analysis, the only significant predictor of total test score was residents' comfort with caring for mechanically ventilated patients (F = 10.963, p = 0.001). Conclusions: EM residents report caring for mechanically ventilated patients frequently, but receive little education on mechanical ventilation. Furthermore, as residents' performance on the assessment tool is only correlated with their self-reported comfort with caring for ventilated patients, these results demonstrate an opportunity for increased educational focus on mechanical ventilation management in EM residency training. (C) 2015 Elsevier Inc. C1 [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Seigel, Todd A.] Rhode Isl Hosp, Dept Emergency Med, Providence, RI USA. [Seigel, Todd A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Strout, Tania D.] Maine Med Ctr, Dept Emergency Med, Portland, ME 04102 USA. [Schneider, Jeffrey I.; Mitchell, Patricia M.] Boston Med Ctr, Dept Emergency Med, Boston, MA USA. [Marcolini, Evie G.] Yale New Haven Med Ctr, Dept Emergency Med, New Haven, CT 06504 USA. [Cocchi, Michael N.] Beth Israel Deaconess Med Ctr, Div Crit Care, Dept Emergency Med, Boston, MA 02215 USA. [Cocchi, Michael N.] Beth Israel Deaconess Med Ctr, Div Crit Care, Dept Anesthesia Crit Care, Boston, MA 02215 USA. [Smithline, Howard A.; Lutfy-Clayton, Lucienne] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Mullen, Marie] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01605 USA. [Ilgen, Jonathan S.] Univ Washington, Sch Med, Div Emergency Med, Seattle, WA 98195 USA. [Richards, Jeremy B.] Beth Israel Deaconess Med Ctr, Dept Internal Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. OI Wilcox, Susan/0000-0001-7477-7531; lutfy-clayton, lucienne/0000-0002-6734-8058 NR 41 TC 3 Z9 3 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2015 VL 48 IS 4 BP 481 EP 491 DI 10.1016/j.jemermed.2014.09.059 PG 11 WC Emergency Medicine SC Emergency Medicine GA CE8RU UT WOS:000352112600023 PM 25497896 ER PT J AU Schmaling, KB Romano, JM Jensen, MP Wilkinson, CW McPherson, S AF Schmaling, Karen B. Romano, Joan M. Jensen, Mark P. Wilkinson, Charles W. McPherson, Sterling TI Salivary Cortisol Responses to Household Tasks Among Couples With Unexplained Chronic Fatigue SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE couples; chronic fatigue syndrome; cortisol; relationship satisfaction ID DIURNAL CORTISOL; QUALITY; ISSUES; LIFE AB This study examined salivary cortisol levels in couples in which one member had unexplained chronic fatigue (CF). The couples completed questionnaires and seven household activities in a laboratory setting and provided salivary cortisol samples prior to and immediately after the activities, as well as again after completing additional questionnaires and debriefing. The couples rated their interactions as similar to those at home, suggesting ecological validity, and patients with CF experienced the activities as involving more exertion than did their partners. The multilevel model results indicated that patients with CF had overall lower cortisol levels and flatter slopes across repeated measurements than did their significant others. Patients' and significant others' cortisol concentrations were significantly associated with each other over time. Furthermore, significant others' cortisol was associated with greater relationship satisfaction and greater observed rates of patients' illness/pain behaviors per minute, but patients' levels of cortisol were not associated with relationship variables. This study is the first to examine cortisol in couples with CF; the results are discussed in terms of implications for future research. C1 [Schmaling, Karen B.] Washington State Univ, Dept Psychol, Vancouver, WA 98686 USA. [Romano, Joan M.; Wilkinson, Charles W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Jensen, Mark P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Wilkinson, Charles W.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [McPherson, Sterling] Washington State Univ, Sch Nursing, Vancouver, WA 98686 USA. RP Schmaling, KB (reprint author), Washington State Univ, Dept Psychol, 14204 NE Salmon Creek Ave, Vancouver, WA 98686 USA. EM Karen.Schmaling@wsu.edu OI Schmaling, Karen/0000-0003-2085-134X FU Chronic Fatigue Association of Minnesota; National Institutes of Health [U19AI38429]; Geriatric Research, Education and Clinical Center; Research and Development Service of the VA Puget Sound Health Care System, Seattle, Washington FX This study was supported by a grant from the Chronic Fatigue Association of Minnesota and National Institutes of Health Grant U19AI38429 Project 4; Charles W. Wilkinson's work was supported in part by the Geriatric Research, Education and Clinical Center and the Research and Development Service of the VA Puget Sound Health Care System, Seattle, Washington. We acknowledge Elizabeth Colasurdo and Carl Sikkema for performance of the cortisol assays and Bethany Osterman for working with the participants. NR 23 TC 1 Z9 1 U1 3 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 EI 1939-1293 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD APR PY 2015 VL 29 IS 2 BP 296 EP 301 DI 10.1037/fam0000074 PG 6 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA CF1PV UT WOS:000352320700017 PM 25844497 ER PT J AU Ricardo, JRD Medhi, J Pineda, R AF da Silva Ricardo, Jose Reinaldo Medhi, Jnanankar Pineda, Roberto TI Femtosecond Laser-Assisted Keratopigmentation for the Management of Visual Disabilities Due to Peripheral Iridectomies SO JOURNAL OF GLAUCOMA LA English DT Article DE keratopigmentation; corneal tattooing; peripheral iridotomy; femtosecond laser ID IRIS; IMPLANTATION; IRIDOTOMY; DEFECTS; EYE AB Purpose: To report the technique and result of keratopigmentation using a femtosecond laser for the treatment of functional visual disabilities caused by peripheral iridectomies. Design: Case report. Methods: Two eyes of 2 patients underwent femtosecond laser-assisted keratopigmentation (FLAK) for moderate to severe visual dysfunction secondary to peripheral iridectomies. The main outcomes measures of the study were changes in visual-related symptoms, cosmesis, and intraoperative surgical complications. Results: Following FLAK, the visual-related symptoms (ghosting, glare, and monocular diplopia) improved in both cases with significant improvement to total elimination of symptoms. No patient lost any lines of visual acuity, and no significant complications were observed during the follow-up period. The cosmetic appearance was reported as very good. Conclusions: FLAK is minimally invasive and results in a significant decrease in the subjective glare and photophobia and even in resolution of monocular diplopia. The cosmetic outcome was also favorable. This technique allows surgeons to correct visual disabilities associated with iris defects with a high success rate while avoiding more aggressive intraocular surgery. C1 [da Silva Ricardo, Jose Reinaldo; Medhi, Jnanankar] Int Council Ophthalmol, San Francisco, CA USA. [da Silva Ricardo, Jose Reinaldo; Medhi, Jnanankar; Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Cornea, Boston, MA 02114 USA. RP Ricardo, JRD (reprint author), Rua Marechal Deodoro 3025, BR-85810200 Cascavel, Parana, Brazil. EM jreinaldo2020@gmail.com.br NR 12 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD APR-MAY PY 2015 VL 24 IS 4 BP E22 EP E24 DI 10.1097/IJG.0000000000000057 PG 3 WC Ophthalmology SC Ophthalmology GA CE9ZQ UT WOS:000352202700002 PM 24777043 ER PT J AU Menendez, ME Mudgal, CS Jupiter, JB Ring, D AF Menendez, Mariano E. Mudgal, Chaitanya S. Jupiter, Jesse B. Ring, David TI Health Literacy in Hand Surgery Patients: A Cross-Sectional Survey SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Health literacy; hand surgery; public health; communication ID SHARED DECISION-MAKING; EMERGENCY-DEPARTMENT; PRIMARY-CARE; OLDER-ADULTS; ITEM BANK; KNOWLEDGE; OUTCOMES; COMMUNICATION; ASSOCIATION; DISPARITIES AB Purpose To determine the prevalence of and factors associated with limited health literacy among outpatients presenting to an urban academic hospital-based hand surgeon. Methods A cohort of 200 English- and Spanish-speaking patients completed the Newest Vital Sign (NVS) health literacy assessment tool, a sociodemographic survey, and 2 Patient-Reported Outcomes Measurement Information System based computerized adaptive testing questionnaires: Patient-Reported Outcomes Measurement Information System Pain Interference and Upper-Extremity Function. The NVS scores were divided into limited (0-3) and adequate (4-6) health literacy. Multivariable regression modeling was used to identify independent predictors of limited health literacy. Results A total of 86 patients (43%) had limited health literacy (English-speaking: 33%; Spanish-speaking: 100%). Factors associated with limited health literacy were advanced age, lower income, and being publicly insured or uninsured. Increasing years of education was a protective factor. Primary language was not included in the logistic regression model because all Spanish-speaking patients had limited health literacy. When evaluating health literacy on a continuum, primary language was the factor that most influenced the NVS scores, accounting for 14% of the variability. Conclusions Limited health literacy was commonplace among patients seeing a hand surgeon, more so in elderly and disadvantaged individuals. We hope our study raises awareness of this issue among hand surgeons and encourages providers to simplify messages and improve communication strategies. Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved. C1 [Menendez, Mariano E.; Mudgal, Chaitanya S.; Jupiter, Jesse B.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Ring, David/0000-0002-6506-4879 NR 53 TC 5 Z9 5 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2015 VL 40 IS 4 BP 798 EP 804 DI 10.1016/j.jhsa.2015.01.010 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CF4LQ UT WOS:000352521000025 PM 25746142 ER PT J AU Mansbach, JM Clark, S Piedra, PA Macias, CG Schroeder, AR Pate, BM Sullivan, AF Espinola, JA Camargo, CA AF Mansbach, Jonathan M. Clark, Sunday Piedra, Pedro A. Macias, Charles G. Schroeder, Alan R. Pate, Brian M. Sullivan, Ashley F. Espinola, Janice A. Camargo, Carlos A., Jr. CA MARC-30 Investigators TI Hospital Course and Discharge Criteria for Children Hospitalized With Bronchiolitis SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID LENGTH-OF-STAY; REAL-TIME PCR; PROSPECTIVE MULTICENTER; PEDIATRIC READMISSION; EMERGENCY-DEPARTMENT; RESPIRATORY RATE; PULSE OXIMETRY; UNITED-STATES; INFANTS; RATES AB BACKGROUNDFor children hospitalized with bronchiolitis, there is uncertainty about the expected inpatient clinical course and when children are safe for discharge. OBJECTIVESExamine the time to clinical improvement, risk of clinical worsening after improvement, and develop discharge criteria. DESIGNProspective multiyear cohort study. SETTINGSixteen US hospitals. PARTICIPANTSConsecutive hospitalized children age <2 years with bronchiolitis. MEASUREMENTWe defined clinical improvement using: (1) retraction severity, (2) respiratory rate, (3) room air oxygen saturation, and (4) hydration status. After meeting improvement criteria, children were considered clinically worse based on the inverse of 1 of these criteria or need for intensive care. RESULTSAmong 1916 children, the median number of days from onset of difficulty breathing until clinical improvement was 4 (interquartile range, 3-7.5 days). Of the total, 1702 (88%) met clinical improvement criteria, with 4% worsening (3% required intensive care). Children who worsened were age <2 months (adjusted odds ratio [AOR]: 3.51; 95% confidence interval [CI]: 2.07-5.94), gestational age <37 weeks (AOR: 1.94; 95% CI: 1.13-3.32), and presented with severe retractions (AOR: 5.55; 95% CI: 2.12-14.50), inadequate oral intake (AOR: 2.54; 95% CI: 1.39-4.62), or apnea (AOR: 2.87; 95% CI: 1.45-5.68). Readmissions were similar for children who did and did not worsen. CONCLUSIONSAlthough children hospitalized with bronchiolitis had wide-ranging recovery times, only 4% worsened after initial improvement. Children who worsened were more likely to be younger, premature infants presenting in more severe distress. For children hospitalized with bronchiolitis, these data may help establish more evidence-based discharge criteria, reduce practice variability, and safely shorten hospital length-of-stay. Journal of Hospital Medicine 2015;10:205-211. (c) 2015 Society of Hospital Medicine C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Macias, Charles G.] Baylor Univ, Texas Childrens Hosp, Dept Pediat, Sect Emergency Med, Houston, TX 77030 USA. [Schroeder, Alan R.] Santa Clara Valley Med Ctr, Dept Pediat, San Jose, CA 95128 USA. [Pate, Brian M.] Univ Missouri, Sch Med, Childrens Mercy Kansas City, Dept Pediat, Kansas City, MO 64108 USA. [Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mansbach, JM (reprint author), Boston Childrens Hosp, Main Clin Bldg,9 South,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu FU National Institutes of Health (Bethesda, MD) [U01 AI-67693, K23 AI-77801] FX This study was supported by grants U01 AI-67693 and K23 AI-77801 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Drs. Mansbach and Piedra have provided consultation to Regeneron Pharmaceuticals. Otherwise, no authors report any potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations. NR 34 TC 5 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2015 VL 10 IS 4 BP 205 EP 211 DI 10.1002/jhm.2318 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CF5XU UT WOS:000352631400001 PM 25627657 ER PT J AU Butala, NM Johnson, BK Dziura, JD Reynolds, JS Bozzo, JE Balcezak, TJ Inzucchi, SE Horwitz, LI AF Butala, Neel M. Johnson, Benjamin K. Dziura, James D. Reynolds, Jesse S. Bozzo, Janis E. Balcezak, Thomas J. Inzucchi, Silvio E. Horwitz, Leora I. TI Association of Inpatient and Outpatient Glucose Management With Inpatient Mortality Among Patients With and Without Diabetes at a Major Academic Medical Center SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; GLYCEMIC CONTROL; CARDIOVASCULAR-DISEASE; MELLITUS; OUTCOMES; COMPLICATIONS AB BACKGROUNDHospitalized patients with diabetes have experienced a disproportionate reduction in mortality over the past decade. OBJECTIVETo examine whether this differential decrease affected all patients with diabetes, and to identify explanatory factors. DESIGNSerial, cross-sectional observational study. SETTINGAcademic medical center. PATIENTSAll adult, nonobstetric patients with an inpatient discharge between January 1, 2000 and December 31, 2010. MEASUREMENTWe assessed in-hospital mortality; inpatient glycemic control (percentage of hospital days with glucose below 70, above 299, and between 70 and 179 mg/dL, and standard deviation of glucose measurements), and outpatient glycemic control (hemoglobin A1c). RESULTSWe analyzed 322,938 admissions, including 76,758 (23.8%) with diabetes. Among 54,645 intensive care unit (ICU) admissions, there was a 7.8% relative reduction in the odds of mortality in each successive year for patients with diabetes, adjusted for age, race, payer, length of stay, discharge diagnosis, comorbidities, and service (odds ratio [OR]: 0.923, 95% confidence interval [CI]: 0.906-0.940). This was significantly greater than the 2.6% yearly reduction for those without diabetes (OR: 0.974, 95% CI: 0.963-0.985; P<0.001 for interaction). In contrast, the greater decrease in mortality among non-ICU patients with diabetes did not reach significance. Results were similar among medical and surgical patients. Among ICU patients with diabetes, the significant decline in mortality persisted after adjustment for inpatient and outpatient glucose control (OR: 0.953, 95% CI: 0.914-0.994). CONCLUSIONSPatients with diabetes in the ICU have experienced a disproportionate reduction in mortality that is not explained by glucose control. Potential explanations include improved cardiovascular risk management or advances in therapies for diseases commonly affecting patients with diabetes. Journal of Hospital Medicine 2015;10:228-235. (c) 2015 Society of Hospital Medicine C1 [Butala, Neel M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Johnson, Benjamin K.; Dziura, James D.; Reynolds, Jesse S.] Yale Univ, Sch Med, Yale Ctr Analyt Sci, New Haven, CT USA. [Bozzo, Janis E.] Yale New Haven Hlth Syst, New Haven, CT USA. [Balcezak, Thomas J.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Inzucchi, Silvio E.] Yale Univ, Sch Med, Dept Med, Sect Endocrinol, New Haven, CT 06510 USA. [Horwitz, Leora I.] NYU, Sch Med, Dept Populat Hlth, Div Healthcare Delivery Sci, New York, NY USA. [Horwitz, Leora I.] NYU, Langone Med Ctr, Ctr Healthcare Innovat & Delivery Sci, New York, NY USA. [Horwitz, Leora I.] NYU, Sch Med, Dept Med, Div Gen Internal Med & Clin Innovat, New York, NY USA. RP Horwitz, LI (reprint author), Dept Populat Hlth, 550 First Ave,TRB Room 607, New York, NY 10016 USA. EM leora.horwitz@nyumc.org OI Horwitz, Leora/0000-0003-1800-6040 FU National Institute on Aging [K08 AG038336]; American Federation for Aging Research through the Paul B. Beeson Career Development Award Program; CTSA from the National Center for Research Resources [UL1 RR024139]; National Center for Advancing Translational Science, components of the National Institutes of Health (NIH); NIH roadmap for Medical Research FX Design and conduct of the study: N. B., J. D., S. I., T. B., L. H. Collection, management, analysis, and interpretation of the data: N. B., B. J., J. D., J. R., J. B., S. I., L. H. Preparation, review, or approval of the manuscript: N. B., B. J., J. D., J. R., S. I., T. B., L. H. Leora Horwitz, MD, 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. Dr. Horwitz is supported by the National Institute on Aging (K08 AG038336) and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program. This publication was also made possible by CTSA grant number UL1 RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH. No funding source had any role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Silvio E. Inzucchi, MD, serves on a Data Safety Monitoring Board for Novo Nordisk, a manufacturer of insulin products used in the hospital setting. The remaining authors declare no conflicts of interest. NR 41 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2015 VL 10 IS 4 BP 228 EP 235 DI 10.1002/jhm.2321 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CF5XU UT WOS:000352631400004 PM 25627860 ER PT J AU Olson, APJ Sahni, N Kim, B Dhaliwal, G AF Olson, Andrew P. J. Sahni, Nishant Kim, Benjamin Dhaliwal, Gurpreet TI Not a Textbook Case SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY; AUTOIMMUNE HEMOLYTIC-ANEMIA C1 [Olson, Andrew P. J.; Sahni, Nishant] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 54555 USA. [Olson, Andrew P. J.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 54555 USA. [Kim, Benjamin] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA. [Kim, Benjamin; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Olson, APJ (reprint author), Univ Minnesota, Sch Med, Div Pediat Hosp Med, Dept Med, 420 Delaware St SE,MMC 741, Minneapolis, MN 55455 USA. EM olso5714@umn.edu NR 14 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2015 VL 10 IS 4 BP 266 EP 270 DI 10.1002/jhm.2319 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CF5XU UT WOS:000352631400010 PM 25647462 ER PT J AU Gupta, A Schiros, CG Gaddam, KK Aban, I Denney, TS Lloyd, SG Oparil, S Dell'Italia, LJ Calhoun, DA Gupta, H AF Gupta, A. Schiros, C. G. Gaddam, K. K. Aban, I. Denney, T. S. Lloyd, S. G. Oparil, S. Dell'Italia, L. J. Calhoun, D. A. Gupta, H. TI Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article ID PRESERVED EJECTION FRACTION; CHRONIC HEART-FAILURE; MYOCARDIAL FIBROSIS; CARDIAC-FUNCTION; DIETARY-SODIUM; ALDOSTERONE; DYSFUNCTION; INHIBITION; COLLAGEN; DISEASE AB We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, P<0.01). No significant change occurred in diastolic filling, relaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high-and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH. C1 [Gupta, A.; Schiros, C. G.; Gaddam, K. K.; Lloyd, S. G.; Oparil, S.; Dell'Italia, L. J.; Calhoun, D. A.; Gupta, H.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aban, I.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Denney, T. S.] Auburn Univ, Dept Elect & Comp Engn, Auburn, AL 36849 USA. [Lloyd, S. G.; Dell'Italia, L. J.; Gupta, H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Gupta, H (reprint author), CVMRI, FACC BDB 101, 1530 3rd Ave South, Birmingham, AL 35294 USA. EM hgupta@uab.edu FU NIH [P50-HL077100, R01-HL104018] FX This study was funded by NIH grants P50-HL077100 (to LJD) and R01-HL104018 (to HG). NR 27 TC 6 Z9 6 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 EI 1476-5527 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD APR PY 2015 VL 29 IS 4 BP 241 EP 246 DI 10.1038/jhh.2014.83 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF4CW UT WOS:000352497200007 PM 25231508 ER PT J AU Lou, S Pan, XX Huang, TW Duan, B Yang, FC Yang, J Xiong, ML Liu, Y Ma, QF AF Lou, Shan Pan, Xiaoxin Huang, Tianwen Duan, Bo Yang, Fu-Chia Yang, Juan Xiong, Mulin Liu, Yang Ma, Qiufu TI Incoherent Feed-Forward Regulatory Loops Control Segregation of C-Mechanoreceptors, Nociceptors, and Pruriceptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE low-threshold c-mechanoreceptors; nociceptors; pruriceptors; Runx1; sensory subtype specification; Zfp521 ID ROOT GANGLION NEURONS; SENSORY NEURONS; SOMATIC SENSATIONS; NEUROPATHIC PAIN; ITCH; DIFFERENTIATION; SPECIFICATION; PROTEIN; EXPRESSION; MICE AB Mammalian skin is innervated by diverse, unmyelinated C fibers that are associated with senses of pain, itch, temperature, or touch. A key developmental question is how this neuronal cell diversity is generated during development. We reported previously that the runt domain transcription factor Runx1 is required to coordinate the development of these unmyelinated cutaneous sensory neurons, including VGLUT3(+) low-threshold c-mechanoreceptors (CLTMs), MrgprD(+) polymodal nociceptors, MrgprA3(+) pruriceptors, MrgprB4(+) c-mechanoreceptors, and others. However, how these Runx1-dependent cutaneous sensory neurons are further segregated is poorly illustrated. Here, we find that the Runx1-dependent transcription factor gene Zfp521 is expressed in, and required for establishing molecular features that define, VGLUT3(+) CLTMs. Furthermore, Runx1 and Zfp521 form a classic incoherent feedforward loop (I-FFL) in controlling molecular identities that normally belong to MrgprD(+) neurons, with Runx1 and Zfp51 playing activator and repressor roles, respectively (in genetic terms). A knock-out of Zfp521 allows prospective VGLUT3 lineage neurons to acquire MrgprD(+) neuron identities. Furthermore, Runx1 might form other I-FFLs to regulate the expression of MrgprA3 and MrgprB4, a mechanism preventing these genes from being expressed in Runx1-persistent VGLUT3(+) and MrgprD(+) neurons. The evolvement of these I-FFLs provides an explanation for how modality-selective sensory subtypes are formed during development and may also have intriguing implications for sensory neuron evolution and sensory coding. C1 [Lou, Shan; Huang, Tianwen; Duan, Bo; Yang, Fu-Chia; Xiong, Mulin; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lou, Shan; Huang, Tianwen; Duan, Bo; Yang, Fu-Chia; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Pan, Xiaoxin; Yang, Juan; Liu, Yang] Hangzhou Normal Univ, Coll Life Sci, Inst Dev & Regenerat Biol, Zhejiang Key Lab Organ Dev & Regenerat, Hangzhou 310029, Zhejiang, Peoples R China. RP Liu, Y (reprint author), Hangzhou Normal Univ, Coll Life Sci, Inst Dev & Regenerat Biol, Zhejiang Key Lab Organ Dev & Regenerat, Hangzhou 310029, Zhejiang, Peoples R China. EM Yang_Liu@idrbio.org; Qiufu_Ma@dfci.harvard.edu FU National Natural Science Foundation of China [31171071]; National Institutes of Health (National Institute of Dental and Craniofacial Research) [R01 DE018025]; National Institutes of Health (National Institute of Neurological Disorders and Stroke) [P01 NS047572] FX Work done in the laboratory of Y.L. was supported by National Natural Science Foundation of China (Grant 31171071). Work done in the laboratory of Q.M. was supported by the National Institutes of Health (National Institute of Dental and Craniofacial Research Grant R01 DE018025 and National Institute of Neurological Disorders and Stroke Grant P01 NS047572). We thank Nancy Speck and Gary Gilliland for the floxed Runx1 mice, Mark Zylka and the Mutant Mouse Regional Resource Centers for the MrgprD-GFP and MrgprD-Cre mice, Xinzhong Dong for the MrgprA3-Cre mice, Susan Dymecki for the ROSA26-Flpe deletor mice, the Allen Brain Institute and the Jackson Laboratory for the Rosa26LSL - tdTomato mice, and the Intellectual and Developmental Disabilities Research Center Mouse Gene Manipulation Core at Boston Children's Hospital for the generation of Zfp521 floxed mice. NR 51 TC 3 Z9 3 U1 0 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2015 VL 35 IS 13 BP 5317 EP 5329 DI 10.1523/JNEUROSCI.0122-15.2015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CF0BT UT WOS:000352208200022 PM 25834056 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI The Influence of Emerging Administrative Scientists An Interview With Anne Miller SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB This department highlights emerging nursing leaders and scientists demonstrating promise in advancing innovation and patient care leadership in practice, policy, research, education, and theory. This interview profiles Anne Miller, PhD, BA, assistant professor jointly appointed to the Center of Interdisciplinary Health Workforce Studies and the School of Nursing at Vanderbilt University Medical Center. C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Boston, MA 02114 USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB 432, Boston, MA 02114 USA. EM jeff.adams@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD APR PY 2015 VL 45 IS 4 BP 192 EP 193 DI 10.1097/NNA.0000000000000183 PG 2 WC Nursing SC Nursing GA CE8GD UT WOS:000352078800005 ER PT J AU Rao, S Rao, S Harvey, HB Avery, L Saini, S Prabhakar, AM AF Rao, Sishir Rao, Sevith Harvey, H. Benjamin Avery, Laura Saini, Sanjay Prabhakar, Anand M. TI Low Back Pain in the Emergency Department-Are the ACR Appropriateness Criteria Being Followed? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE ACR Appropriateness Criteria; imaging for low back pain; ED imaging ID AMERICAN-COLLEGE; DECISION-SUPPORT; UNITED-STATES; PRIMARY-CARE; HEALTH-CARE AB Purpose: To assess the prevalence of appropriate imaging among emergency department (ED) patients with low back pain. Methods: Our level-1 ED records were retrospectively searched for patients with a chief compliant of "low back pain" from January to April 2013. Of 624 patients, 100 were randomly selected and analyzed for their demographics, presentation, imaging, treatment, and outcomes. The study indication for imaging was compared with the ACR Appropriateness Criteria, and the indication was deemed appropriate if it received a rating of >= 5. Results: The mean age of the study population was 48 years (50% women, 50% men). The majority presented with acute ox acute on chronic low back pain (94 patients), and half had a precipitating event (50 patients). A total of 28 (28%) patients underwent imaging in the ED; 24 (24%) had outpatient imaging; 54 (54%) had neither ED nor outpatient imaging. In all, 96% (27 of 28) of patients imaged in the ED, and 96% (23 of 24) imaged as outpatients, were appropriately imaged. Of patients who did not undergo imaging, 96% (52 of 54) were appropriately not imaged. A total of 76 patients (76%) had follow-up after discharge: of these, 42 (55%) had resolution or return of pain to baseline with conservative management; 18 (24%) had improvement with intervention (epidural steroid injection or kyphoplasty); 8 (10%) improved with surgery; and 8 had persistent pain (11%). Conclusions: The majority of patients presenting to the ED with low back pain did not undergo imaging. The vast majority of those who underwent imaging were appropriately imaged, based on the ACR Appropriateness Criteria. C1 [Rao, Sishir; Rao, Sevith; Harvey, H. Benjamin; Avery, Laura; Saini, Sanjay; Prabhakar, Anand M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu NR 22 TC 2 Z9 2 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2015 VL 12 IS 4 BP 364 EP 369 DI 10.1016/j.jacr.2014.10.020 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9RL UT WOS:000352181000012 PM 25703700 ER PT J AU Bettmann, MA Oikarinen, H Rehani, M Holmberg, O Perez, MD Naidoo, A Do, KH Dreyer, K Ebdon-Jackson, S AF Bettmann, Michael A. Oikarinen, Helja Rehani, Madan Holmberg, Ola Perez, Maria del Rosario Naidoo, Anusha Do, Kyung-Hyun Dreyer, Keith Ebdon-Jackson, Steve TI Clinical Imaging Guidelines Part 4: Challenges in Identifying, Engaging and Collaborating With Stakeholders SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Imaging stakeholders; clinical imaging guidelines; guideline development roles AB The effective development and use of clinical imaging guidelines requires an understanding of who the stakeholders are, what their interests in the process are, and what roles they should play. If the appropriate stakeholders are not engaged in the right roles, it is unlikely that clinical imaging guidelines will be successfully developed, relied on, and actually used. Some stakeholders are obvious: for the development of clinical imaging guidelines, both imagers and those who request examinations, such as general practitioners, internists, and medical specialists, must be involved. To gain acceptance, other relevant groups are stakeholders, including medical societies, other health care professionals, insurers, health IT experts and vendors, and patients. The role of stakeholders must be dictated by their specific interest. For some, involvement in the creation of guidelines is the right role. For others, such as regulators or insurers, reviews or invitations to comment are required, and for others, such as medical educators, it is probably sufficient to provide information and create awareness. Only through a careful consideration of who the stakeholders are and what are their interests are the successful development, acceptance, and use of clinical imaging guidelines likely to occur. Future efforts must focus on collaboration, particularly among groups that create clinical imaging guidelines and those that can support their use, and on regulatory roles and mandates. C1 [Bettmann, Michael A.] Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. [Oikarinen, Helja] Oulu Univ Hosp, Dept Diagnost Radiol, Oulu, Finland. [Rehani, Madan] Harvard Univ, Sch Med, Boston, MA USA. [Rehani, Madan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Holmberg, Ola] IAEA, Vienna Int Ctr, Radiat Protect Patients Unit, A-1400 Vienna, Austria. [Perez, Maria del Rosario] WHO, Cluster Family Womens & Childrens Hlth FWC, Dept Publ Hlth Environm & Social Determinants Hlt, Radiat Programme, CH-1211 Geneva, Switzerland. [Naidoo, Anusha] RANZCR, Stand Practice & Accreditat, Sydney, NSW, Australia. [Do, Kyung-Hyun] Asan Med Ctr, Korean Soc Radiol, Seoul, South Korea. [Dreyer, Keith] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dreyer, Keith] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ebdon-Jackson, Steve] Publ Hlth England Chilton, Med Exposure Regulatory Infrastruct Team CRCE, Didcot, Oxon, England. RP Bettmann, MA (reprint author), 70 Three Mile Rd, Etna, NH 03750 USA. EM mabettmann@gmail.com FU World Health Organization [001] NR 22 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2015 VL 12 IS 4 BP 370 EP 375 DI 10.1016/j.jacr.2014.07.020 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9RL UT WOS:000352181000013 PM 25842016 ER PT J AU Harvey, HB Alkasab, TK Pandharipande, PV Zhao, J Halpern, EF Salazar, GM Abujudeh, HH Rosenthal, DI Gazelle, GS AF Harvey, H. Benjamin Alkasab, Tarik K. Pandharipande, Pari V. Zhao, Jing Halpern, Elkan F. Salazar, Gloria M. Abujudeh, Hani H. Rosenthal, Daniel I. Gazelle, G. Scott TI Radiologist Compliance With Institutional Guidelines for Use of Nonroutine Communication of Diagnostic Imaging Results SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiology; critical results; Joint Commission; nonroutine communication; quality and safety ID ERRORS; CARE AB Purpose: The aim of this study was to evaluate radiologist compliance with institutional guidelines for nonroutine communication of diagnostic imaging results. Methods: From July 2012 through September 2013, 7,401 completed advanced imaging cases were retrospectively reviewed by groups of 3 or more radiologists. The reviewing radiologists were asked to reach consensus on two questions related to nonroutine communication: (1) "Does the report describe a finding which requires nonroutine communication to the patient's physicians?" and if so, (2) "Were the department's guidelines for nonroutine communication followed?" Consensus judgments were aggregated and analyzed on the basis of subspecialty, level of acuity per the guidelines, and type of communication used. Results: Of the 7,401 studies reviewed, 960 (13.0%) were deemed, to require nonroutine results communication. The need for nonroutine communication was most frequent with CT (16.6%), followed by MRI (11.1%) and ultrasound (3.4%). For the divisions studied, nonroutine communication was most frequently needed in thoracic (37.9%), followed by neurologic (17.3%), emergency (15.8%), cardiac (13.7%), musculoskeletal (4.4%), and abdominal (0.7%) imaging. Of the cases requiring nonroutine communication, 39 (4%) yielded consensus that the guidelines were not appropriately followed: 21% (n = 8) involved level 1 findings (critical), 41% (n = 16) involved level 2 findings (acute), and 38% (n = 15) involved level 3 findings (nonacute). Failures of communication involving level 1 findings primarily involved neurologic imaging, including 4 cases of new cerebral infarct and 3 cases of new intracranial hemorrhage. Conclusions: Established guidelines for nonroutine communication are appropriately applied and durable, underscoring the high yield of formalizing and implementing these guidelines across practice settings. C1 [Harvey, H. Benjamin; Alkasab, Tarik K.; Pandharipande, Pari V.; Halpern, Elkan F.; Salazar, Gloria M.; Abujudeh, Hani H.; Rosenthal, Daniel I.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Harvey, H. Benjamin; Alkasab, Tarik K.; Pandharipande, Pari V.; Halpern, Elkan F.; Salazar, Gloria M.; Abujudeh, Hani H.; Rosenthal, Daniel I.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Pandharipande, Pari V.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Zhao, Jing] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM hbharvey@partners.org NR 22 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2015 VL 12 IS 4 BP 376 EP 384 DI 10.1016/j.jacr.2014.08.013 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9RL UT WOS:000352181000014 PM 25441481 ER PT J AU Mulshine, JL Gierada, DS Armato, SG Avila, RS Yankelevitz, DF Kazerooni, EA McNitt-Gray, MF Buckler, AJ Sullivan, DC AF Mulshine, James L. Gierada, David S. Armato, Samuel G., III Avila, Rick S. Yankelevitz, David F. Kazerooni, Ella A. McNitt-Gray, Michael F. Buckler, Andrew J. Sullivan, Daniel C. TI Role of the Quantitative Imaging Biomarker Alliance in Optimizing CT for the Evaluation of Lung Cancer Screen-Detected Nodules SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Lung cancer screening; pulmonary nodules; quantitative imaging biomarker; low-dose CT scans; metrology ID VOLUMETRIC CT; INTEROBSERVER; VARIABILITY; GUIDELINES; RATES AB The Quantitative Imaging Biomarker Alliance (QIBA) is a multidisciplinary consortium sponsored by the RSNA to define processes that enable the implementation and advancement of quantitative imaging methods described in a QIBA profile document that outlines the process to reliably and accurately measure imaging features. A QIBA profile includes factors such as technical (product-specific) standards, user activities, and relationship to a clinically meaningful metric, such as with nodule measurement in the course of CT screening for lung cancer. In this report, the authors describe how the QIBA approach is being applied to the measurement of small pulmonary nodules such as those found during low-dose CT-based lung cancer screening. All sources of variance with irnaging measurement were defined for this process. Through a process of experimentation, literature review, and assembly of expert opinion, the strongest evidence was used to define how to best implement each step in the imaging acquisition and evaluation process. This systematic approach to implementing a quantitative imaging biomarker with standardized specifications for image acquisition and postprocessing for a specific quantitative measurement of a pulmonary nodule results in consistent performance characteristics of the measurement (eg, bias and variance). Implementation of the QIBA small nodule profile may allow more efficient and effective clinical management of the diagnostic workup of individuals found to have suspicious pulmonary nodules in the course of lung cancer screening evaluation. C1 [Mulshine, James L.] Rush Univ, Chicago, IL 60612 USA. [Gierada, David S.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Armato, Samuel G., III] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Avila, Rick S.] US Dept Vet Affairs, Washington, DC USA. [Yankelevitz, David F.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Kazerooni, Ella A.] Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. [McNitt-Gray, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Buckler, Andrew J.] Elucid Bioimaging Inc, Wenham, MA USA. [Sullivan, Daniel C.] Duke Univ, Dept Radiol, Durham, NC 27710 USA. RP Mulshine, JL (reprint author), Rush Univ, 1735 W Harrison St,Suite 206, Chicago, IL 60612 USA. EM jmulshin@rush.edu OI Buckler, Andrew/0000-0002-0786-4835 NR 29 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2015 VL 12 IS 4 BP 390 EP 395 DI 10.1016/j.jacr.2014.12.003 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9RL UT WOS:000352181000016 PM 25842017 ER PT J AU Kohli, M Dreyer, KJ Geis, JR AF Kohli, Marc Dreyer, Keith J. Geis, J. Raymond TI The Imaging 3.0 Informatics Scorecard SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Imaging 3.0; imaging informatics; radiology information technology; innovation; clinical decision support AB Imaging 3.0 is a radiology community initiative to empower radiologists to create and demonstrate value for their patients, referring physicians, and health systems. In image-guided health care, radiologists contribute to the entire health care process, well before and after the actual examination, and out to the point at which they guide clinical decisions and affect patient outcome. Because imaging is so pervasive, radiologists who adopt Imaging 3.0 concepts in their practice can help their health care systems provide consistently high-quality care at reduced cost. By doing this, radiologists become more valuable in the new health care setting. The authors describe how informatics is critical to embracing Imaging 3.0 and present a scorecard that can be used to gauge a radiology group's informatics resources and capabilities. C1 [Kohli, Marc] Indiana Univ Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. [Dreyer, Keith J.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Geis, J. Raymond] Adv Med Imaging Consultants PC, Aurora, CO USA. [Geis, J. Raymond] Univ Colorado, Sch Med, Ft Collins, CO USA. RP Geis, JR (reprint author), 3401 Shore Rd, Ft Collins, CO 80524 USA. EM raym.geis@gmail.com NR 14 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2015 VL 12 IS 4 BP 396 EP 402 DI 10.1016/j.jacr.2014.11.017 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9RL UT WOS:000352181000017 PM 25842018 ER PT J AU Boland, GW Duszak, R AF Boland, Giles W. Duszak, Richard, Jr. TI The Challenges in Delivering the Value Chain SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. RP Boland, GW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 3 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD APR PY 2015 VL 12 IS 4 BP 409 EP 411 DI 10.1016/j.jacr.2015.01.002 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE9RL UT WOS:000352181000019 PM 25842019 ER PT J AU Geetha, D Specks, U Stone, JH Merkel, PA Seo, P Spiera, R Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Fessler, BJ Ding, L Tchao, NK Ikle, D Jepson, B Brunetta, P Fervenza, FC AF Geetha, Duvuru Specks, Ulrich Stone, John H. Merkel, Peter A. Seo, Philip Spiera, Robert Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Fessler, Barri J. Ding, Linna Tchao, Nadia K. Ikle, David Jepson, Brett Brunetta, Paul Fervenza, Fernando C. CA Rituximab ANCA-Associated TI Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ANTIBODY-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; REMISSION-INDUCTION; SERUM CREATININE; POLYANGIITIS; MAINTENANCE; PREDICTION; EXPERIENCE; RELAPSE; INDEX AB Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m(2) x 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3-6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegener's Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m(2); P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids. C1 [Geetha, Duvuru; Seo, Philip] Johns Hopkins Univ, Div Nephrol, Baltimore, MD USA. [Geetha, Duvuru; Seo, Philip] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Specks, Ulrich; Fervenza, Fernando C.] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Rochester, MN 55901 USA. [Specks, Ulrich; Fervenza, Fernando C.] Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN 55901 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Spiera, Robert] Hosp Special Surg, Div Rheumatol, New York, NY 10021 USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin Fdn, Ctr Vasculitis Care & Res, Cleveland, OH 44195 USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, NL-9713 AV Groningen, Netherlands. [St Clair, E. William] Duke Univ, Div Rheumatol & Immunol, Durham, NC USA. [Fessler, Barri J.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Tchao, Nadia K.] Immune Tolerance Network, San Francisco, CA USA. [Ikle, David; Jepson, Brett] Rho Inc, Chapel Hill, NC USA. [Brunetta, Paul] Genentech Inc, San Francisco, CA 94080 USA. RP Fervenza, FC (reprint author), Mayo Clin, Coll Med, Div Nephrol & Hypertens, 200 First St SW, Rochester, MN 55901 USA. EM fervenza.fernando@mayo.edu OI Carey, John/0000-0001-7292-2328 FU NIH [N01-AI-15416]; National Institute of Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation; Genentech; Biogen Idec.; Clinical and Translational Science Award (CTSA) from the National Center for Research Resources (NCRR) [UL1-RR024150-01]; CTSA from the NCRR [UL1-RR025005, UL1-RR025771, NIH M01-RR00533]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [K24-AR049185, K23-AR052820]; NIAMS [K24-AR02224]; Arthritis Foundation Investigator Award FX This research was performed as a project of the Immune Tolerance Network (NIH contract N01-AI-15416; protocol number ITN021AI), an international clinical research consortium headquartered at the University of California, San Francisco.; Supported by the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec. At the Mayo Clinic, the trial was supported by a Clinical and Translational Science Award (CTSA) grant (UL1-RR024150-01) from the National Center for Research Resources (NCRR). At Johns Hopkins, the trial was supported by a CTSA grant (UL1-RR025005) from the NCRR and by grants (K24-AR049185, to J.H.S. and K23-AR052820, to P.S.) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). At Boston University, the trial was supported by CTSA grants (UL1-RR025771 and NIH M01-RR00533) from the NCRR and a grant (K24-AR02224) from the NIAMS (all to P.A.M.) and an Arthritis Foundation Investigator Award (to P.M.). NR 20 TC 19 Z9 20 U1 2 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2015 VL 26 IS 4 BP 976 EP 985 DI 10.1681/ASN.2014010046 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CE7UZ UT WOS:000352048700024 PM 25381429 ER PT J AU Havens, K Ertl, K Moin, T Vasti, E Makki, F Hughes, M Youles, B Damschroder, L Richardson, C AF Havens, Kathryn Ertl, Kristyn Moin, Tannaz Vasti, Elena Makki, Fatima Hughes, Maria Youles, Bradley Damschroder, Laura Richardson, Caroline TI Women Veterans' Early Experiences with a Web-Based Diabetes Prevention Program SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Havens, Kathryn] Zablocki VA Med Ctr, Milwaukee, WI USA. [Ertl, Kristyn] Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, Milwaukee, WI 53226 USA. [Moin, Tannaz; Vasti, Elena] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Makki, Fatima; Hughes, Maria; Youles, Bradley; Damschroder, Laura; Richardson, Caroline] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. NR 0 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 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2015 VL 24 IS 4 MA P41 BP 17 EP 18 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CF5YE UT WOS:000352632500042 ER PT J AU Yadav, P Leung, N Sanders, PW Cockwell, P AF Yadav, Punit Leung, Nelson Sanders, Paul W. Cockwell, Paul TI The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease SO KIDNEY INTERNATIONAL LA English DT Review DE monoclonal gammopathy; monoclonal gammopathy of renal significance; multiple myeloma; serum free light chains ID URINE IMMUNOFIXATION ELECTROPHORESIS; MONOCLONAL GAMMOPATHIES; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; PROTEIN ELECTROPHORESIS; QUANTITATIVE ASSESSMENT; AL-AMYLOIDOSIS; SERUM; COMBINATION; POPULATION AB Kidney involvement is common in paraprotein-related diseases. A diversity of clinical presentations and histopathological features can occur secondary to tissue injury caused by precipitation or deposition of a clonal immunoglobulin, usually an immunoglobulin light chain. The paraprotein is either produced by multiple myeloma or by a clone of B-cell lineage that does not fulfill diagnostic criteria for multiple myeloma. The recent introduction of serum immunoglobulin free light chain assays, which accurately quantify both light chain isotypes to produce a ratio that indicates the presence or absence of a light chain paraprotein, is a major clinical development. However, as the interpretation of the assay can be challenging, the aim of this review is to clarify the role of serum and urinary light chain assays in the screening and diagnosis of paraprotein-related kidney disease. C1 [Yadav, Punit; Cockwell, Paul] Queen Elizabeth Hosp, Dept Renal Med, Birmingham B15 2WB, W Midlands, England. [Yadav, Punit; Cockwell, Paul] Univ Birmingham, Coll Med & Dent Sci, Div Immun & Infect, Birmingham, W Midlands, England. [Leung, Nelson] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Leung, Nelson] Mayo Clin, Div Haematol, Rochester, MN USA. [Sanders, Paul W.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Cockwell, P (reprint author), Queen Elizabeth Hosp, Dept Renal Med, Mindelsohn Way, Birmingham B15 2WB, W Midlands, England. EM paul.cockwell@uhb.nhs.uk OI Cockwell, Paul/0000-0003-1975-266X; Leung, Nelson/0000-0002-5651-1411 FU CSRD VA [I01 CX001326]; NIDDK NIH HHS [P30 DK079337] NR 29 TC 2 Z9 2 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD APR PY 2015 VL 87 IS 4 BP 692 EP 697 DI 10.1038/ki.2014.333 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CE9QZ UT WOS:000352179800007 PM 25296094 ER PT J AU Pang, P Jin, XH Proctor, BM Farley, M Roy, N Chin, MS von Andrian, UH Vollmann, E Perro, M Hoffman, RJ Chung, J Chauhan, N Mistri, M Muslin, AJ Bonventre, JV Siedlecki, AM AF Pang, Paul Jin, Xiaohua Proctor, Brandon M. Farley, Michelle Roy, Nilay Chin, Matthew S. von Andrian, Ulrich H. Vollmann, Elisabeth Perro, Mario Hoffman, Ryan J. Chung, Joseph Chauhan, Nikita Mistri, Murti Muslin, Anthony J. Bonventre, Joseph V. Siedlecki, Andrew M. TI RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; ischemia reperfusion; renin angiotensin system ID VASCULAR SMOOTH-MUSCLE; INDUCED HYPERTENSION; AT(2) RECEPTORS; UP-REGULATION; KAPPA-B; CELLS; ISCHEMIA; AT(1); ATHEROSCLEROSIS; DYSFUNCTION AB Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the G alpha-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 min unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury, blood flow was decreased in the inner cortex of wild-type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild-type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18h after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (V5MCs) to secrete the macrophage chemoattractant RANTES, a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating G alpha protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by 12 MRI compared with transgenic and non-transgenic mice after the 10 min injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation. C1 [Pang, Paul; Chung, Joseph; Chauhan, Nikita; Mistri, Murti; Bonventre, Joseph V.; Siedlecki, Andrew M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard Inst Med,Renal Div,Dept Internal Med, Boston, MA 02115 USA. [Jin, Xiaohua; Proctor, Brandon M.; Muslin, Anthony J.] Washington Univ, Sch Med, St Louis, MO USA. [Farley, Michelle] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Roy, Nilay] Partners Healthcare, Boston, MA USA. [Chin, Matthew S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [von Andrian, Ulrich H.; Vollmann, Elisabeth; Perro, Mario] Harvard Univ, Sch Med, Boston, MA 02115 USA. [von Andrian, Ulrich H.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. [Hoffman, Ryan J.] Wesleyan Univ, Middletown, CT USA. RP Siedlecki, AM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard Inst Med,Renal Div,Dept Internal Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM asiedlecki@partners.org FU NIH [R01 HL061567, P30 DK079333, K08DK089002, R37DK039773, RO1AI069259, PO1AI078897]; UAB/UCSD 'Brien Core Center for Acute Kidney Injury Research [NIH P30 DK 079337]; Shared Instrumentation Grant at Beth Israel Deaconess Medical Center [S10 RR028792] FX This work was supported by NIH grants R01 HL061567 (AJM), P30 DK079333 (AMS and AJM), K08DK089002 (AMS), R37DK039773 (JVB), RO1AI069259 (UHvA) and PO1AI078897 (UHvA), UAB/UCSD 'Brien Core Center for Acute Kidney Injury Research (NIH P30 DK 079337), and a Shared Instrumentation Grant S10 RR028792 at Beth Israel Deaconess Medical Center. NR 43 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD APR PY 2015 VL 87 IS 4 BP 771 EP 783 DI 10.1038/ki.2014.364 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA CE9QZ UT WOS:000352179800015 PM 25469849 ER PT J AU Paykov, ME Nelson, RG Knowler, WC Cheng, YL Krolewski, AS Niewczas, MA AF Paykov, Meda E. Nelson, Robert G. Knowler, William C. Cheng, Yiling Krolewski, Andrzej S. Niewczas, Monika A. TI Elevation of circulating TNF receptors 1 and 2 increases the risk of end-stage renal disease in American Indians with type 2 diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE diabetic nephropathy; ESRD; TNF ID TUMOR-NECROSIS-FACTOR; APOPTOSIS-INDUCING LIGAND; INSULIN-RESISTANCE; KIDNEY-FUNCTION; ADIPOSE-TISSUE; HUMAN OBESITY; PIMA-INDIANS; FACTOR-ALPHA; NEPHROPATHY; EXPRESSION AB In Caucasians with type 2 diabetes, circulating TNF receptors 1 (TNFR1) and 2 (INFR2) predict end-stage renal disease (ESRD). Here we examined this relationship in a longitudinal cohort study of American Indians with type 2 diabetes with measured glomerular filtration rate (mGFR, iothalamate) and urinary albumin-to-creatinine ratio (ACR). ESRD was defined as dialysis, kidney transplant, or death attributed to diabetic kidney disease. Age-gender-adjusted incidence rates and incidence rate ratios of ESRD were computed by Mantel-Haenszel stratification. The hazard ratio of ESRD was assessed per interquartile range increase in the distribution of each TNFR after adjusting for baseline age, gender, mean blood pressure, HbA1c, ACR, and mGFR. Among the 193 participants, 62 developed ESRD and 25 died without E5RD during a median follow-up of 9.5 years. The age-gender-adjusted incidence rate ratio of ESRD was higher among participants in the highest versus lowest quartile for TNFR1 (6.6, 95% confidence interval (Cl) 3.3-13.3) or TNFR2 (8.8, 95% Cl 4.3-18.0). In the fully adjusted model, the risk of ESRD per interquartile range increase was 1.6 times (95% Cl 1.1-2.2) as high for TNFR1 and 1.7 times (95% CI 1.2-2.3) as high for TNFR2. Thus, elevated serum concentrations of TNFR1 or TNFR2 are associated with increased risk of ESRD in American Indians with type 2 diabetes after accounting for traditional risk factors including ACR and mGFR. C1 [Paykov, Meda E.; Cheng, Yiling] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Nelson, Robert G.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. [Krolewski, Andrzej S.; Niewczas, Monika A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Krolewski, Andrzej S.; Niewczas, Monika A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Nelson, RG (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, 1550 East Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health (NIH) [DRC P30DK036836, DK41526, DK67638] FX This study was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and by grants from the National Institutes of Health (NIH): DRC P30DK036836 to MAN; DK41526 and DK67638 to ASK. NR 48 TC 0 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD APR PY 2015 VL 87 IS 4 BP 812 EP 819 DI 10.1038/ki.2014.330 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CE9QZ UT WOS:000352179800020 ER PT J AU Weber, JS D'Angelo, SP Minor, D Hodi, FS Gutzmer, R Neyns, B Hoeller, C Khushalani, NI Miller, WH Lao, CD Linette, GP Thomas, L Lorigan, P Grossmann, KF Hassel, JC Maio, M Sznol, M Ascierto, PA Mohr, P Chmielowski, B Bryce, A Svane, IM Grob, JJ Krackhardt, AM Horak, C Lambert, A Yang, AS Larkin, J AF Weber, Jeffrey S. D'Angelo, Sandra P. Minor, David Hodi, F. Stephen Gutzmer, Ralf Neyns, Bart Hoeller, Christoph Khushalani, Nikhil I. Miller, Wilson H., Jr. Lao, Christopher D. Linette, Gerald P. Thomas, Luc Lorigan, Paul Grossmann, Kenneth F. Hassel, Jessica C. Maio, Michele Sznol, Mario Ascierto, Paolo A. Mohr, Peter Chmielowski, Bartosz Bryce, Alan Svane, Inge M. Grob, Jean-Jacques Krackhardt, Angela M. Horak, Christine Lambert, Alexandre Yang, Arvin S. Larkin, James TI Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID ANTI-PD-1 ANTIBODY; RESPONSE CRITERIA; SAFETY; IPILIMUMAB; PD-1; CANCER; EXPRESSION; TOLERANCE; LYMPHOMA; BLOCKADE AB Background Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients at 90 sites in 14 countries. Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. We stratified randomisation by BRAF mutation status, tumour expression of PD-L1, and previous best overall response to ipilimumab. We used permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with ClinicalTrials.gov, number NCT01721746. Findings Between Dec 21, 2012, and Jan 10, 2014, we screened 631 patients, randomly allocating 272 patients to nivolumab and 133 to ICC. Confirmed objective responses were reported in 38 (31.7%, 95% CI 23.5-40.8) of the first 120 patients in the nivolumab group versus five (10.6%, 3.5-23.1) of 47 patients in the ICC group. Grade 3-4 adverse events related to nivolumab included increased lipase (three [1%] of 268 patients), increased alanine aminotransferase, anaemia, and fatigue (two [1%] each); for ICC, these included neutropenia (14 [14%] of 102), thrombocytopenia (six [6%]), and anaemia (five [5%]). We noted grade 3-4 drug-related serious adverse events in 12 (5%) nivolumab-treated patients and nine (9%) patients in the ICC group. No treatment-related deaths occurred. Interpretation Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need. C1 [Weber, Jeffrey S.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [D'Angelo, Sandra P.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [D'Angelo, Sandra P.] Weill Cornell Med Coll, New York, NY USA. [Minor, David] Calif Pacific Ctr Melanoma Res, San Francisco, CA USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gutzmer, Ralf] Hannover Med Sch, Hannover, Germany. [Neyns, Bart] Univ Ziekenhuis Brussel, Brussels, Belgium. [Hoeller, Christoph] Med Univ Vienna, Vienna, Austria. [Khushalani, Nikhil I.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Miller, Wilson H., Jr.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada. [Lao, Christopher D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Linette, Gerald P.] Washington Univ, St Louis, MO USA. [Thomas, Luc] CHU Lyon, Lyon, France. [Lorigan, Paul] Christie Hosp, Manchester, Lancs, England. [Grossmann, Kenneth F.] Huntsman Canc Inst, Salt Lake City, UT USA. [Hassel, Jessica C.] Univ Heidelberg Hosp, German Canc Res Ctr, Heidelberg, Germany. [Maio, Michele] Univ Hosp, Ist Toscano Tumori, Med Oncol & Immunotherapy, Siena, Italy. [Sznol, Mario] Yale Canc Ctr, New Haven, CT USA. [Ascierto, Paolo A.] Ist Nazl Tumori Fdn G Pascale, Naples, Italy. [Mohr, Peter] Elbe Kliniken Buxtehude, Buxtehude, Germany. [Chmielowski, Bartosz] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Bryce, Alan] Mayo Clin, Dept Med, Scottsdale, AZ USA. [Svane, Inge M.] Herlev Hosp, Dept Oncol, Copenhagen, Denmark. [Grob, Jean-Jacques] Aix Marseille Univ, Hop Timone, Marseille, France. [Krackhardt, Angela M.] Tech Univ Munich, Sch Med, Dept Med 2, D-80290 Munich, Germany. [Horak, Christine; Yang, Arvin S.] Bristol Myers Squibb, Princeton, NJ USA. [Lambert, Alexandre] Bristol Myers Squibb, Braine lAlleud, Belgium. [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England. RP Weber, JS (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. EM jeffrey.weber@moffitt.org RI Lorigan, Paul/J-6898-2015; OI Lorigan, Paul/0000-0002-8875-2164; Chmielowski, Bartosz/0000-0002-2374-3320; coral, sandra/0000-0002-1308-3082; Svane, Inge Marie/0000-0002-9451-6037; Bryce, Alan H./0000-0002-0206-3895 FU Bristol-Myers Squibb; National Institute for Health Research Royal Marsden Hospital/Institute of Cancer Research Biomedical Research Centre for Cancer FX The study was funded by Bristol-Myers Squibb. We thank the patients who participated in this study and their families for their support; investigators and members of the clinical study team, particularly Lori Volles and Gwen Ouellette of Bristol-Myers Squibb, for implementation of the trial; and Dako for collaborative development of the automated PD-L1 immunohistochemistry assay. JL is supported by the National Institute for Health Research Royal Marsden Hospital/Institute of Cancer Research Biomedical Research Centre for Cancer. Medical writing, editing, and graphic support was provided by StemScientific, an Ashfield Company (Lyndhurst, New Jersey, USA), particularly Wayne Peng and Karin McGlynn, funded by Bristol-Myers Squibb. NR 30 TC 410 Z9 424 U1 19 U2 43 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2015 VL 16 IS 4 BP 375 EP 384 DI 10.1016/S1470-2045(15)70076-8 PG 10 WC Oncology SC Oncology GA CE7LA UT WOS:000352020000044 PM 25795410 ER PT J AU Petrylak, DP Vogelzang, NJ Budnik, N Wiechno, PJ Sternberg, CN Doner, K Bellmunt, J Burke, JM de Olza, MO Choudhury, A Gschwend, JE Kopyltsov, E Flechon, A Van As, N Houede, N Barton, D Fandi, A Jungnelius, U Li, SY de Wit, R Fizazi, K AF Petrylak, Daniel P. Vogelzang, Nicholas J. Budnik, Nikolay Wiechno, Pawel Jan Sternberg, Cora N. Doner, Kevin Bellmunt, Joaquim Burke, John M. de Olza, Maria Ochoa Choudhury, Ananya Gschwend, Juergen E. Kopyltsov, Evgeny Flechon, Aude Van As, Nicolas Houede, Nadine Barton, Debora Fandi, Abderrahim Jungnelius, Ulf Li, Shaoyi de Wit, Ronald Fizazi, Karim TI Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID MITOXANTRONE PLUS PREDNISONE; ADVANCED SOLID TUMORS; HIGH-DOSE CALCITRIOL; III TRIAL; COMBINATION; THALIDOMIDE; MEN; AFLIBERCEPT; BEVACIZUMAB; ZIBOTENTAN AB Background Patients with metastatic castration-resistant prostate cancer have few treatment options. We investigated the safety and efficacy of lenalidomide, an immunomodulatory agent with anti-angiogenic properties, in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned chemotherapy-naive patients with progressive metastatic castration-resistant prostate cancer in a 1: 1 ratio to receive docetaxel (75 mg/m(2)) on day 1 and prednisone (5 mg twice daily) on days 1-21 and either lenalidomide (25 mg) or placebo once daily on days 1-14 of each 21 day treatment cycle. Permuted block randomisation was done with an interactive voice response system and stratified by Eastern Cooperative Oncology Group performance status, geographic region, and type of disease progression. Clinicians, patients, and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy analysis was by intention to treat. Patients who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00988208. Findings 1059 patients were enrolled and randomly assigned between Nov 11, 2009, and Nov 23, 2011 (533 to the lenalidomide group and 526 to the control group), and 1046 patients received study treatment (525 in the lenalidomide group and 521 in the placebo group). At data cutoff (Jan 13, 2012) after a median follow-up of 8 months (IQR 5-12), 221 patients had died: 129 in the lenalidomide group and 92 in the placebo group. Median overall survival was 17.7 months (95% CI 14.8-18.8) in the lenalidomide group and not reached in the placebo group (hazard ratio [HR] 1.53, 95% CI 1.17-2.00, p= 0.0017). The trial was subsequently closed early due to futility. The number of deaths that occurred during treatment or less than 28 days since the last dose were similar in both groups (18 [3%] of 525 patients in the lenalidomide group vs 13 [2%] of 521 patients). 109 (21%) patients in the lenalidomide group and 78 (15%) in the placebo group died more than 28 days from last dose, mainly due to disease progression. At least one grade 3 or higher adverse event was reported in 381 (73%) of 525 patients receiving lenalidomide and 303 (58%) of 521 patients receiving placebo. Grade 3-4 neutropenia (114 [22%] for lenalidomide vs 85 [16%] for placebo), febrile neutropenia (62 [12%] vs 23 [4%]), diarrhoea (37 [7%] vs 12 [2%]), pneumonia (24 [5%] vs five [1%]), dyspnoea (22 [4%] vs nine [2%]), asthenia (27 [5%] vs 17 [3%]), and pulmonary embolism (32 [6%] vs seven [1%]) occurred more frequently in the lenalidomide group than in the placebo group. Interpretation Overall survival with the combination of lenalidomide, docetaxel, and prednisone was significantly worse than with docetaxel and prednisone for chemotherapy-naive men with metastatic, castration-resistant prostate cancer. Further research with this treatment combination is not warranted. C1 [Petrylak, Daniel P.] Yale Canc Ctr, Dept Med, Div Oncol, New Haven, CT 06520 USA. [Vogelzang, Nicholas J.; Budnik, Nikolay] US Oncol Res, Houston, TX USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Budnik, Nikolay] OAO Russian Railways, NSHI Dorozhnaya Clin Hosp, Rostov Na Donu, Russia. [Wiechno, Pawel Jan] Ctr Onkol, Inst Marii Sklodowskiej Curie, Dept Urooncol, Warsaw, Poland. [Sternberg, Cora N.] San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Doner, Kevin] Texas Oncol, Austin, TX USA. [Bellmunt, Joaquim] Univ Hosp Mar, IMIM, Barcelona, Spain. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Burke, John M.] Rocky Mt Canc Ctr, Aurora, CO USA. [de Olza, Maria Ochoa] Catalan Inst Oncol, Dept Med, Barcelona, Spain. [Choudhury, Ananya] Univ Manchester, Christie NHS Fdn Trust, Dept Clin Oncol, Manchester, Lancs, England. [Choudhury, Ananya] Univ Manchester, Inst Canc Sci, Manchester, Lancs, England. [Gschwend, Juergen E.] Tech Univ Munich, Rechts Isar Med Ctr, Dept Urol, D-80290 Munich, Germany. [Kopyltsov, Evgeny] State Inst Healthcare Reg Clin Oncol Dispensary, Omsk, Russia. [Flechon, Aude] Ctr Leon Berard, Dept Med Oncol, F-69373 Lyon, France. [Van As, Nicolas] Royal Marsden Hosp, Dept Clin Oncol, London SW3 6JJ, England. [Houede, Nadine] Univ Caremeau, Grp Hosp, Dept Med Oncol, Nimes, France. [Barton, Debora; Fandi, Abderrahim; Jungnelius, Ulf; Li, Shaoyi] Celgene Corp, Summit, NJ USA. [de Wit, Ronald] ErasmusMC Canc Inst, Rotterdam, Netherlands. [Fizazi, Karim] Univ Paris Sud, Inst Gustave Roussy, Dept Canc Med, Villejuif, France. RP Petrylak, DP (reprint author), Yale Canc Ctr, Dept Med, Div Oncol, POB 208028, New Haven, CT 06520 USA. EM daniel.petrylak@yale.edu OI van As, Nicholas/0000-0001-6829-8788; Choudhury, Ananya/0000-0002-3561-6580 FU Celgene Corporation; NIHR RM/ICR Biomedical Research Centre FX This study was funded by Celgene Corporation. Medical writing services were provided by Ronald van Olffen (Excerpta Medica BV), funded by Celgene Corporation. NVA acknowledges support from the NIHR RM/ICR Biomedical Research Centre. The authors are fully responsible for content and editorial decisions for this report. NR 35 TC 32 Z9 35 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2015 VL 16 IS 4 BP 417 EP 425 DI 10.1016/S1470-2045(15)70025-2 PG 9 WC Oncology SC Oncology GA CE7LA UT WOS:000352020000048 PM 25743937 ER PT J AU Fassnacht, M Berruti, A Baudin, E Demeure, MJ Gilbert, J Haak, H Kroiss, M Quinn, DI Hesseltine, E Ronchi, CL Terzolo, M Choueiri, TK Poondru, S Fleege, T Rorig, R Chen, JH Stephens, AW Worden, F Hammer, GD AF Fassnacht, Martin Berruti, Alfredo Baudin, Eric Demeure, Michael J. Gilbert, Jill Haak, Harm Kroiss, Matthias Quinn, David I. Hesseltine, Elizabeth Ronchi, Cristina L. Terzolo, Massimo Choueiri, Toni K. Poondru, Srinivasu Fleege, Tanya Rorig, Ramona Chen, Jihong Stephens, Andrew W. Worden, Francis Hammer, Gary D. TI Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study SO LANCET ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PLATINUM-BASED CHEMOTHERAPY; ADVANCED SOLID TUMORS; FACTOR-I; ANTIBODY CIXUTUMUMAB; INSULIN-RECEPTORS; ADJUVANT MITOTANE; GENE-EXPRESSION; INHIBITOR; CANCER AB Background Adrenocortical carcinoma is a rare, aggressive cancer for which few treatment options are available. Linsitinib (OSI-906) is a potent, oral small molecule inhibitor of both IGF-1R and the insulin receptor, which has shown acceptable tolerability and preliminary evidence of anti-tumour activity. We assessed linsitinib against placebo to investigate efficacy in patients with advanced adrenocortical carcinoma. Methods In this international, double-blind, placebo-controlled phase 3 study, adult patients with histologically confirmed locally advanced or metastatic adrenocortical carcinoma were recruited at clinical sites in nine countries. Patients were randomly assigned (2:1) twice-daily 150 mg oral linsitinib or placebo via a web-based, centralised randomisation system and stratified according to previous systemic cytotoxic chemotherapy for adrenocortical carcinoma, Eastern Cooperative Oncology Group performance status, and use of one or more oral antihyperglycaemic therapy at randomisation. Allocation was concealed by blinded block size and permuted block randomisation. The primary endpoint was overall survival, calculated from date of randomisation until death from any cause. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00924989. Findings Between Dec 2, 2009, and July 11, 2011, 139 patients were enrolled, of whom 90 were assigned to linsitinib and 49 to placebo. The trial was unblinded on March 19, 2012, based on data monitoring committee recommendation due to the failure of linsitinib to increase either progression-free survival or overall survival. At database lock and based on 92 deaths, no difference in overall survival was noted between linsitinib and placebo (median 323 days [95% CI 256-507] vs 356 days [249-556]; hazard ratio 0.94 [95% CI 0.61-1.44]; p= 0.77). The most common treatment-related adverse events of grade 3 or worse in the linsitinib group were fatigue (three [3%] patients vs no patients in the placebo group), nausea (two [2%] vs none), and hyperglycaemia (two [2%] vs none). No adverse events in the linsitinib group were deemed to be treatment related; one death (due to sepsis and megacolon) in the placebo group was deemed to be treatment related. Interpretation Linsitinib did not increase overall survival and so cannot be recommended as treatment for this general patient population. Further studies of IGF-1R and insulin receptor inhibitors, together with genetic profiling of responders, might pave the way toward individualised and improved therapeutic options in adrenocortical carcinoma. C1 [Fassnacht, Martin] Univ Wurzburg, Univ Hosp, Endocrine & Diabet Unit, Dept Internal Med 1, D-97070 Wurzburg, Germany. [Fassnacht, Martin; Kroiss, Matthias] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97070 Wurzburg, Germany. [Fassnacht, Martin; Ronchi, Cristina L.] Univ Hosp Wurzburg, Res Unit, Cent Lab, Wurzburg, Germany. [Berruti, Alfredo] Univ Brescia, Dept Med Surg Specialties Radiol Sci & Publ Hlth, Brescia, Italy. [Baudin, Eric] Inst Gustave Roussy, Dept Nucl Med & Endocrine Tumors, Villejuif, France. [Demeure, Michael J.] Translat Genom Res Inst, Phoenix, AZ USA. [Gilbert, Jill] Vanderbilt Univ Sch Med, Nashville, TN USA. [Haak, Harm] Maxima Med Ctr, Dept Internal Med, Eindhoven, Netherlands. [Haak, Harm] Maastricht Univ, Med Ctr, Dept Internal Med, NL-6200 MD Maastricht, Netherlands. [Haak, Harm] Maastricht Univ, Dept Hlth Serv Res, NL-6200 MD Maastricht, Netherlands. [Haak, Harm] CAPHRI Sch Publ Hlth & Primary Care, Maastricht, Netherlands. [Quinn, David I.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Hesseltine, Elizabeth; Worden, Francis; Hammer, Gary D.] Univ Michigan Hlth Syst, Ctr Comprehens Canc, Endocrine Oncol Program, Ann Arbor, MI 48109 USA. [Terzolo, Massimo] Univ Turin, Turin, Italy. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Poondru, Srinivasu; Fleege, Tanya; Rorig, Ramona; Chen, Jihong] Astellas Pharma Global Dev, Northbrook, IL USA. [Stephens, Andrew W.] Piramal Imaging, Berlin, Germany. RP Hammer, GD (reprint author), Univ Michigan, Endocrine Oncol Program, 109 Zina Pitcher Pl,1528 BSRB, Ann Arbor, MI 48109 USA. EM ghammer@umich.edu RI Quinn, David/F-4343-2015; OI Quinn, David/0000-0002-1411-0417; Terzolo, Massimo/0000-0002-4171-2851; Ronchi, Cristina/0000-0001-5020-2071 FU Astellas FX This trial was funded by Astellas. We thank professional medical writers Melissa Kirk (Scientific Connexions, Lyndhurst, NJ, USA) and Roberta Sottocornola (CircleScience, Macclesfield, UK) for assistance in the preparation of the report. Writing support was funded by Astellas. We further thank the investigators, study sites, and senior advisors listed in the appendix for their participation in the study. NR 30 TC 47 Z9 48 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2015 VL 16 IS 4 BP 426 EP 435 DI 10.1016/S1470-2045(15)70081-1 PG 10 WC Oncology SC Oncology GA CE7LA UT WOS:000352020000049 PM 25795408 ER PT J AU Oser, MG Niederst, MJ Sequist, LV Engelman, JA AF Oser, Matthew G. Niederst, Matthew J. Sequist, Lecia V. Engelman, Jeffrey A. TI Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin SO LANCET ONCOLOGY LA English DT Review ID GROWTH-FACTOR RECEPTOR; CISPLATIN PLUS GEMCITABINE; TYROSINE KINASE INHIBITORS; RANDOMIZED PHASE-3 TRIAL; EGFR MUTATIONS; 1ST-LINE TREATMENT; OPEN-LABEL; PULMONARY ADENOCARCINOMA; NEUROENDOCRINE CARCINOMA; ACQUIRED-RESISTANCE AB Lung cancer is the most common cause of cancer deaths worldwide. The two broad histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Although NSCLC and SCLC are commonly thought to be different diseases owing to their distinct biology and genomic abnormalities, the idea that these malignant disorders might share common cells of origin has been gaining support. This idea has been supported by the unexpected findings that a subset of NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase inhibitors develops. Additionally, other case reports have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of their distinct lineages. Here, we summarise the published clinical observations and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies pointing to common potential cells of origin, and speculate how the distinct paths of differentiation are determined by the genomics of each disease. C1 [Oser, Matthew G.; Niederst, Matthew J.; Sequist, Lecia V.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Oser, Matthew G.; Niederst, Matthew J.; Sequist, Lecia V.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. EM jengelman@partners.org FU [R01 CA137008]; [T32 CA009172] FX This work was funded by R01 CA137008 (JAE) and T32 CA009172 (MGO). NR 64 TC 42 Z9 44 U1 6 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2015 VL 16 IS 4 BP E165 EP E172 PG 8 WC Oncology SC Oncology GA CE7LA UT WOS:000352020000022 PM 25846096 ER PT J AU Loughran, TP Zickl, L Olson, TL Wang, V Zhang, D Rajala, HLM Hasanali, Z Bennett, JM Lazarus, HM Litzow, MR Evens, AM Mustjoki, S Tallman, MS AF Loughran, T. P., Jr. Zickl, L. Olson, T. L. Wang, V. Zhang, D. Rajala, H. L. M. Hasanali, Z. Bennett, J. M. Lazarus, H. M. Litzow, M. R. Evens, A. M. Mustjoki, S. Tallman, M. S. TI Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998) SO LEUKEMIA LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; LYMPHOPROLIFERATIVE DISEASE; RHEUMATOID-ARTHRITIS; STAT3; APOPTOSIS; ACTIVATION; SURVIVAL; PROTEIN; FAS; PHOSPHORYLATION AB Failure to undergo activation-induced cell death due to global dysregulation of apoptosis is the pathogenic hallmark of large granular lymphocyte (LGL) leukemia. Consequently, immunosuppressive agents are rational choices for treatment. This first prospective trial in LGL leukemia was a multicenter, phase 2 clinical trial evaluating methotrexate (MTX) at 10 mg/m(2) orally weekly as initial therapy (step 1). Patients failing MTX were eligible for treatment with cyclophosphamide at 100 mg orally daily (step 2). The overall response in step 1 was 38% with 95% confidence interval (CI): 26 and 53%. The overall response in step 2 was 64% with 95% CI: 35 and 87%. The median overall survival for patients with anemia was 69 months with a 95% CI lower bound of 46 months and an upper bound not yet reached. The median overall survival for patients with neutropenia has not been reached 13 years from study activation. Serum biomarker studies confirmed the inflammatory milieu of LGL but were not a priori predictive of response. We identify a gene expression signature that correlates with response and may be STAT3 mutation driven. Immunosuppressive therapies have efficacy in LGL leukemia. Gene signature and mutational profiling may be an effective tool in determining whether MTX is an appropriate therapy. C1 [Loughran, T. P., Jr.; Olson, T. L.; Zhang, D.; Hasanali, Z.] Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA. [Zickl, L.; Wang, V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rajala, H. L. M.; Mustjoki, S.] Univ Helsinki, Cent Hosp, Hematol Res Unit, Helsinki, Finland. [Bennett, J. M.] Univ Rochester, Dept Med, Hematol Oncol, Rochester, NY USA. [Lazarus, H. M.] Case Western Reserve Univ, Ireland Canc Ctr, Hematol Oncol, Dept Med, Cleveland, OH 44106 USA. [Litzow, M. R.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Evens, A. M.] Tufts Canc Ctr, Boston, MA USA. [Tallman, M. S.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA. [Loughran, T. P., Jr.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Loughran, T. P., Jr.; Olson, T. L.] Penn State Canc Inst, Hershey, PA USA. [Evens, A. M.] Univ Massachusetts, Sch Med, Dept Med, Hematol Oncol, Worcester, MA USA. [Tallman, M. S.] Northwestern Univ, Sch Med, Chicago, IL USA. RP Loughran, TP (reprint author), Univ Virginia, Ctr Canc, POB 800839, Charlottesville, VA 22908 USA. EM tploughran@virginia.edu FU Public Health Service from the NCI [CA23318, CA66636, CA21115, CA73590, CA11083, CA14548, CA13650, CA17145, CA78724, CA90633, CA94872, CA133525]; NIH; DHHS FX We acknowledge Rob Brucklacher of Penn State Hershey Functional Genomics for performing microarrays. We also thank Arjan van Adrichem for the creation of the Y640F STAT3 plasmid. Su-Fern Tan and Alex Wendling provided assistance with the conversion of figures. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA73590, CA11083, CA14548, CA13650, CA17145, CA78724, CA90633, CA94872 and CA133525 from the NCI, NIH and the DHHS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI. NR 29 TC 18 Z9 18 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD APR PY 2015 VL 29 IS 4 BP 886 EP 894 DI 10.1038/leu.2014.298 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CF5GY UT WOS:000352586700016 PM 25306898 ER PT J AU Okeyo-Owuor, T White, BS Chatrikhi, R Mohan, DR Kim, S Griffith, M Ding, L Ketkar-Kulkarni, S Hundal, J Laird, KM Kielkopf, CL Ley, TJ Walter, MJ Graubert, TA AF Okeyo-Owuor, T. White, B. S. Chatrikhi, R. Mohan, D. R. Kim, S. Griffith, M. Ding, L. Ketkar-Kulkarni, S. Hundal, J. Laird, K. M. Kielkopf, C. L. Ley, T. J. Walter, M. J. Graubert, T. A. TI U2AF1 mutations alter sequence specificity of pre-mRNA binding and splicing SO LEUKEMIA LA English DT Article ID RIBONUCLEOPROTEIN AUXILIARY FACTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; SMALL-SUBUNIT; FACTOR U2AF(65); FACTOR U2AF(35); IN-VIVO; RECOGNITION; SF3B1; REQUIREMENT AB We previously identified missense mutations in the U2AF1 splicing factor affecting codons S34 (S34F and S34Y) or Q157 (Q157R and Q157P) in 11% of the patients with de novo myelodysplastic syndrome (MDS). Although the role of U2AF1 as an accessory factor in the U2 snRNP is well established, it is not yet clear how these mutations affect splicing or contribute to MDS pathophysiology. We analyzed splice junctions in RNA-seq data generated from transfected CD34+ hematopoietic cells and found significant differences in the abundance of known and novel junctions in samples expressing mutant U2AF1 (S34F). For selected transcripts, splicing alterations detected by RNA-seq were confirmed by analysis of primary de novo MDS patient samples. These effects were not due to impaired U2AF1 (S34F) localization as it co-localized normally with U2AF2 within nuclear speckles. We further found evidence in the RNA-seq data for decreased affinity of U2AF1 (S34F) for uridine (relative to cytidine) at the e-3 position immediately upstream of the splice acceptor site and corroborated this finding using affinity-binding assays. These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis. C1 [Okeyo-Owuor, T.; White, B. S.; Mohan, D. R.; Kim, S.; Ketkar-Kulkarni, S.; Ley, T. J.; Walter, M. J.; Graubert, T. A.] Washington Univ, Div Oncol, Dept Internal Med, St Louis, MO USA. [White, B. S.; Griffith, M.; Ding, L.; Hundal, J.; Ley, T. J.] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA. [Chatrikhi, R.; Laird, K. M.; Kielkopf, C. L.] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. RP Graubert, TA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 North Grove St,LWH 204, Boston, MA 02114 USA. EM tgraubert@partners.org OI Graubert, Timothy/0000-0002-7710-1171 FU Barnes-Jewish Hospital Foundation [7603-55]; NIH/NCI SPORE in Leukemia [P50CA171063]; NIH/NCI [1K12CA167540]; Clinical and Translational Award from the NIH National Center for Advancing Translational Sciences [UL1 TR000448]; Howard Hughes Medical Institute Physician-Scientist Early Career Award; Leukemia and Lymphoma Society Scholar Award; Leukemia and Lymphoma Society Translational Research Award; NIH [R01 GM070503]; [P30CA91842] FX This work was supported by Barnes-Jewish Hospital Foundation (7603-55 to BSW), an NIH/NCI SPORE in Leukemia (P50CA171063 to TAG, MJW and BSW), an NIH/NCI grant (1K12CA167540 to BSW), a Clinical and Translational Award from the NIH National Center for Advancing Translational Sciences (UL1 TR000448 to BSW), a Howard Hughes Medical Institute Physician-Scientist Early Career Award and Leukemia and Lymphoma Society Scholar Award (to MJW), a Leukemia and Lymphoma Society Translational Research Award (to TAG), and NIH R01 GM070503 (to CLK). Technical assistance was provided by the Alvin J. Siteman Cancer Center High Speed Cell Sorting core (supported in part by P30CA91842), Molecular Microbiology Imaging Facility (MMIF), the Genome Technology Access Center (GTAC) and the Genome Institute. Additional technical support was provided by Masayo Izumi. We are grateful to Dr Christopher R Cabanski for assistance with edgeR and Dr Cara Lunn Shirai for helpful scientific discussions. NR 34 TC 15 Z9 15 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD APR PY 2015 VL 29 IS 4 BP 909 EP 917 DI 10.1038/leu.2014.303 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CF5GY UT WOS:000352586700019 PM 25311244 ER PT J AU Ortega, M Bhatnagar, H Lin, AP Wang, L Aster, JC Sill, H Aguiar, RCT AF Ortega, M. Bhatnagar, H. Lin, A-P Wang, L. Aster, J. C. Sill, H. Aguiar, R. C. T. TI A microRNA-mediated regulatory loop modulates NOTCH and MYC oncogenic signals in B- and T-cell malignancies SO LEUKEMIA LA English DT Article ID C-MYC; MYELOID-LEUKEMIA; LYMPHOMA; MUTATIONS; CANCER; PATHWAY; TARGET; TUMORIGENESIS; PROGRESSION; ACTIVATION AB Growing evidence suggests that microRNAs (miRNAs) facilitate the cross-talk between transcriptional modules and signal transduction pathways. MYC and NOTCH1 contribute to the pathogenesis of lymphoid malignancies. NOTCH induces MYC, connecting two signaling programs that enhance oncogenicity. Here we show that this relationship is bidirectional and that MYC, via a miRNA intermediary, modulates NOTCH. MicroRNA-30a (miR-30a), a member of a family of miRNAs that are transcriptionally suppressed by MYC, directly binds to and inhibits NOTCH1 and NOTCH2 expression. Using a murine model and genetically modified human cell lines, we confirmed that miR-30a influences NOTCH expression in a MYC-dependent fashion. In turn, through genetic modulation, we demonstrated that intracellular NOTCH1 and NOTCH2, by inducing MYC, suppressed miR-30a. Conversely, pharmacological inhibition of NOTCH decreased MYC expression and ultimately de-repressed miR-30a. Examination of genetic models of gain and loss of miR-30a in diffuse large B-cell lymphoma (DLBCL) and T-acute lymphoblastic leukemia (T-ALL) cells suggested a tumor-suppressive role for this miRNA. Finally, the activity of the miR-30a-NOTCH-MYC loop was validated in primary DLBCL and T-ALL samples. These data define the presence of a miRNA-mediated regulatory circuitry that may modulate the oncogenic signals originating from NOTCH and MYC. C1 [Ortega, M.; Bhatnagar, H.; Lin, A-P; Wang, L.; Aguiar, R. C. T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. [Aster, J. C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Aster, J. C.] Harvard Univ, Sch Med, Boston, MA USA. [Sill, H.] Med Univ Graz, Div Hematol, Graz, Austria. [Aguiar, R. C. T.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Aguiar, R. C. T.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Aguiar, R. C. T.] Audie Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Aguiar, RCT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM aguiarr@uthscsa.edu OI Sill, Heinz/0000-0003-0993-4371 FU National Cancer Institute [R01-CA138747]; Veterans Administration Merit Award [I01-BX001882]; National Cancer Institute Cancer Center Support Grant [P30 CA054174] FX We thank H Bouamar for technical help in generating the microRNA sponges, A Weng for suggestions and the Flow Cytometry Shared Resource Facility at UTHSCSA for the cell sorting. This work was supported by a grant from the National Cancer Institute (R01-CA138747), a Veterans Administration Merit Award (I01-BX001882) and a National Cancer Institute Cancer Center Support Grant (P30 CA054174). NR 38 TC 9 Z9 11 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD APR PY 2015 VL 29 IS 4 BP 968 EP 976 DI 10.1038/leu.2014.302 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CF5GY UT WOS:000352586700025 PM 25311243 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI John E. Walker-Nobel Prize in Chemistry in 1997 SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Boston Med Sch, Boston, MA USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 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 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2015 VL 90 IS 4 BP E41 EP E41 DI 10.1016/j.mayocp.2012.01.034 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CE9XW UT WOS:000352197900002 PM 25841265 ER PT J AU Arnason, T Brown, LS Goldsmith, JD Anderson, W O'Brien, BH Wilson, C Winter, H Lauwers, GY AF Arnason, Thomas Brown, Lan S. Goldsmith, Jeffrey D. Anderson, William O'Brien, Blake H. Wilson, Claire Winter, Harland Lauwers, Gregory Y. TI Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients SO MODERN PATHOLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; PLASMA-CELL INFILTRATION; EOSINOPHILIC ESOPHAGITIS; AUTOIMMUNE PANCREATITIS; IGG4-RELATED DISEASE; COLITIS; EXPRESSION; CHILDREN; ANEMIA; ULCER AB Collagenous gastritis is a rare condition defined histologically by a superficial subepithelial collagen layer. This study further characterizes the morphologic spectrum of collagenous gastritis by evaluating a multi-institutional series of 40 patients (26 female and 14 male). The median age at onset was 16 years (range 3-89 years), including 24 patients (60%) under age 18. Twelve patients (30%) had associated celiac disease, collagenous sprue, or collagenous colitis. Hematoxylin and eosin slides were reviewed in biopsies from all patients and tenascin, gastrin, eotaxin, and IgG4/IgG immunohistochemical stains were applied to a subset. The distribution of subepithelial collagen favored the body/fundus in pediatric patients and the antrum in adults. There were increased surface intraepithelial lymphocytes (>25 lymphocytes/100 epithelial cells) in five patients. Three of these patients had associated celiac and/or collagenous sprue/colitis, while the remaining two had increased duodenal lymphocytosis without specific etiology. An eosinophil-rich pattern (430 eosinophils/high power field) was seen in 21/40 (52%) patients. Seven patients' biopsies demonstrated atrophy of the gastric corpus mucosa. Tenascin immunohistochemistry highlighted the subepithelial collagen in all 21 specimens evaluated and was a more sensitive method of collagen detection in biopsies from two patients with subtle subepithelial collagen. No increased eotaxin expression was identified in 16 specimens evaluated. One of the twenty-three biopsies tested had increased IgG4-positive cells (100/high power field) with an IgG4/IgG ratio of 55%. In summary, collagenous gastritis presents three distinct histologic patterns including a lymphocytic gastritis-like pattern, an eosinophil-rich pattern, and an atrophic pattern. Eotaxin and IgG4 were not elevated enough to implicate these pathways in the pathogenesis. Tenascin immunohistochemistry can be used as a sensitive method of collagen detection. C1 [Arnason, Thomas; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Gastrointestinal Pathol Serv,Massachusetts Gen Ho, Boston, MA 02115 USA. [Arnason, Thomas] Dalhousie Univ, Queen Elizabeth II Hlth Sci Ctr, Div Anat Pathol, Halifax, NS, Canada. [Brown, Lan S.] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Brown, Lan S.] Envoi Pathol, Brisbane, Qld, Australia. [Goldsmith, Jeffrey D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol,Childrens Hosp Boston, Boston, MA 02215 USA. [Anderson, William] GastroEnterol Associates Ocala, Ocala, FL USA. [O'Brien, Blake H.] Sullivan Nicolaides Pathol, Brisbane, Qld, Australia. [Wilson, Claire] Providence Alaska Med Ctr, Anchorage, AK USA. [Winter, Harland] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Arnason, T (reprint author), Dalhousie Univ, Div Anat Pathol, 734a,MacKenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. EM thomas.arnason@cdha.nshealth.ca RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 32 TC 1 Z9 1 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2015 VL 28 IS 4 BP 533 EP 544 DI 10.1038/modpathol.2014.119 PG 12 WC Pathology SC Pathology GA CF1OF UT WOS:000352315000008 PM 25234289 ER PT J AU Cleven, AHG Nardi, V Ok, CY Goswami, M Dal Cin, P Zheng, ZL Lafrate, AJ Hamid, MAA Wang, SA Hasserjian, RP AF Cleven, Arjen H. G. Nardi, Valentina Ok, Chi Young Goswami, Maitrayee Dal Cin, Paola Zheng, Zongli Lafrate, A. John Hamid, Myrurgia A. Abdul Wang, Sa A. Hasserjian, Robert P. TI High p53 protein expression in therapy-related myeloid neoplasms is associated with adverse karyotype and poor outcome SO MODERN PATHOLOGY LA English DT Article ID RISK MYELODYSPLASTIC SYNDROMES; CHRONIC LYMPHOCYTIC-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; COMPLEX KARYOTYPE; TP53 MUTATIONS; MODEL; CORRELATE; RELEVANT; DELETION; DEL(5Q) AB Identification of p53-positive cells by immunohistochemistry in bone marrow from primary myelodysplastic syndrome patients correlates with the presence of TP53 mutations and poor prognosis. Mutations in the tumor suppressor gene TP53 are more frequent in therapy-related acute myeloid leukemia and myelodysplastic syndrome than in de novo disease, but the role of p53 immunohistochemistry in the therapy-related setting has not been specifically investigated. We studied p53 protein immunoreactivity in bone marrow biopsies of therapy-related myeloid neoplasms and correlated protein expression with TP53 mutation status, clinicopathologic features and outcome. We first studied 32 patients with therapy-related acute myeloid leukemia and 63 patients with therapy-related myelodysplastic syndrome/chronic myelomonocytic leukemia from one institution and then validated our results in a separate group of 32 patients with therapy-related acute myeloid leukemia and 56 patients with therapy-related myelodysplastic syndrome from a different institution. Strong p53 immunostaining in > 1% of bone marrow cells was highly predictive of a TP53 gene mutation (P<0.0001) and was strongly associated with a high-risk karyotype (P<0.0001). The presence of >= 1% p53 strongly positive cells was associated with poorer overall and disease-specific survival, particularly in the subset of patients treated with stem-cell transplantation. In a multivariable Cox regression model, the presence of >= 1% p53 strongly expressing cells was an independent prognostic marker for overall survival in both cohorts, with hazard ratios of 3.434 (CI: 1.751-6.735, P<0.0001) and 3.156 (CI: 1.502-6.628, P = 0.002). Our data indicate that p53 protein expression, evaluated in bone marrow biopsies by a widely available immunohistochemical method, prognostically stratifies patients with therapy-related myeloid neoplasms independent of other risk factors. p53 immunostaining thus represents an easily applicable method to assess risk in therapy-related acute myeloid leukemia/myelodysplastic syndrome patients. C1 [Cleven, Arjen H. G.] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. [Nardi, Valentina; Zheng, Zongli; Lafrate, A. John; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ok, Chi Young; Goswami, Maitrayee; Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Dal Cin, Paola] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, Boston, MA 02115 USA. [Hamid, Myrurgia A. Abdul] Maastricht Univ, Dept Pathol, Med Ctr, NL-6200 MD Maastricht, Netherlands. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN244,55 Fruit St, Boston, MA 02114 USA. EM rhasserjian@partners.org RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 NR 29 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2015 VL 28 IS 4 BP 552 EP 563 DI 10.1038/modpathol.2014.153 PG 12 WC Pathology SC Pathology GA CF1OF UT WOS:000352315000010 PM 25412846 ER PT J AU Jones, RT Abedalthagafi, MS Brahmandam, M Greenfield, EA Hoang, MP Louis, DN Hornick, JL Santagata, S AF Jones, Robert T. Abedalthagafi, Malak S. Brahmandam, Mohan Greenfield, Edward A. Hoang, Mai P. Louis, David N. Hornick, Jason L. Santagata, Sandro TI Cross-reactivity of the BRAF VE1 antibody with epitopes in axonemal dyneins leads to staining of cilia SO MODERN PATHOLOGY LA English DT Article ID CELL LUNG-CANCER; MUTATIONS; TUMORS; CRANIOPHARYNGIOMAS; METASTASES; PITUITARY; FEATURES; SAMPLES; AKT1 AB Antibodies that recognize neo-epitopes in tumor cells are valuable tools in the evaluation of tissue biopsy or resection specimens. The VE1 antibody that recognizes the V600E-mutant BRAF protein is one such example. We have recently shown that the vast majority of papillary craniopharyngiomas-tumors that arise in the sellar or suprasellar regions of the brain-harbor BRAF V600E mutations. The VE1 antibody can be effective in discriminating papillary craniopharyngioma from adamantinomatous craniopharyngioma, which harbors mutations in CTNNB1 and not BRAF. While further characterizing the use of the VE1 antibody in the differential diagnosis of suprasellar lesions, we found that the VE1 antibody stains the epithelial cells lining Rathke's cleft cysts with very strong staining of the cilia of these cells. We used targeted sequencing to show that Rathke's cleft cysts do not harbor the BRAF V600E mutation. Moreover, we found that the VE1 antibody reacts strongly with cilia in various structures-the bronchial airways, the fallopian tubes, the nasopharynx, and the epididymis-as well as with the flagella of sperm. In addition, VE1 reacts strongly with the cilia of the ependymal lining of the brain and with the cilia-containing microlumens of ependymoma tumors. There is significant sequence homology between the synthetic peptide (amino acid 596-606 of BRAF V600E: GLATEKSRWSG) that was used to generate the VE1 antibody and regions of multiple axonemal dynein heavy chain proteins (eg, DNAH2, DNAH7, and DNAH12). These proteins are major components of the axonemes of cilia and flagella where they drive the sliding of microtubules. In ELISA assays, we show that the VE1 antibody recognizes epitopes from these proteins. A familiarity with the cross-reactivity of the VE1 antibody with epitopes of proteins in cilia is of value when evaluating tissues stained with this important clinical antibody. C1 [Jones, Robert T.; Abedalthagafi, Malak S.; Hornick, Jason L.; Santagata, Sandro] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Neuropathol,Dept Pathol, Boston, MA 02115 USA. [Brahmandam, Mohan; Greenfield, Edward A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Monoclonal Antibody Core, Boston, MA 02115 USA. [Brahmandam, Mohan; Greenfield, Edward A.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Hoang, Mai P.; Louis, David N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Santagata, Sandro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Santagata, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Neuropathol,Dept Pathol,Harvard Inst Med, HIM 921,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ssantagata@partners.org NR 24 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2015 VL 28 IS 4 BP 596 EP 606 DI 10.1038/modpathol.2014.150 PG 11 WC Pathology SC Pathology GA CF1OF UT WOS:000352315000014 PM 25412847 ER PT J AU Zhang, XL Joehanes, R Chen, BH Huan, TX Ying, SX Munson, PJ Johnson, AD Levy, D O'Donnell, CJ AF Zhang, Xiaoling Joehanes, Roby Chen, Brian H. Huan, Tianxiao Ying, Saixia Munson, Peter J. Johnson, Andrew D. Levy, Daniel O'Donnell, Christopher J. TI Identification of common genetic variants controlling transcript isoform variation in human whole blood SO NATURE GENETICS LA English DT Article ID SYNONYMOUS SNPS; EXPRESSION QTL; DISEASE; FRAMINGHAM; GENOME; ASSOCIATIONS; POPULATION; TISSUES; TRAITS; DESIGN AB An understanding of the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of common disease. The available evidence from splicing quantitative trait locus (sQTL) studies has been limited to small samples. We performed genome-wide screening to identify SNPs that might control mRNA splicing in whole blood collected from 5,257 Framingham Heart Study participants. We identified 572,333 cis sQTLs involving 2,650 unique genes. Many sQTL-associated genes (40%) undergo alternative splicing. Using the National Human Genome Research Institute (NHGRI) genome-wide association study (GWAS) catalog, we determined that 528 unique sQTLs were significantly enriched for 8,845 SNPs associated with traits in previous GWAS. In particular, we found 395 (4.5%) GWAS SNPs with evidence of cis sQTLs but not gene-level cis expression quantitative trait loci (eQTLs), suggesting that sQTL analysis could provide additional insights into the functional mechanism underlying GWAS results. Our findings provide an informative sQTL resource for further characterizing the potential functional roles of SNPs that control transcript isoforms relevant to common diseases. C1 [Zhang, Xiaoling; Joehanes, Roby; Chen, Brian H.; Huan, Tianxiao; Johnson, Andrew D.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Zhang, Xiaoling; Joehanes, Roby; Chen, Brian H.; Huan, Tianxiao; Johnson, Andrew D.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Joehanes, Roby; Ying, Saixia; Munson, Peter J.] US NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP O'Donnell, CJ (reprint author), NHLBI, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. EM odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013; OI Chen, Brian/0000-0001-9065-3301 FU US NIH [N01-HC-25195]; NHLBI, Division of Intramural Research FX The FHS is funded by US NIH contract N01-HC-25195; this work was also supported by the NHLBI, Division of Intramural Research. NR 45 TC 19 Z9 19 U1 0 U2 10 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 APR PY 2015 VL 47 IS 4 BP 345 EP U92 DI 10.1038/ng.3220 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CE6CH UT WOS:000351922900009 PM 25685889 ER PT J AU Onengut-Gumuscu, S Chen, WM Burren, O Cooper, NJ Quinlan, AR Mychaleckyj, JC Farber, E Bonnie, JK Szpak, M Schofield, E Achuthan, P Guo, H Fortune, MD Stevens, H Walker, NM Ward, LD Kundaje, A Kellis, M Daly, MJ Barrett, JC Cooper, JD Deloukas, P Todd, JA Wallace, C Concannon, P Rich, SS AF Onengut-Gumuscu, Suna Chen, Wei-Min Burren, Oliver Cooper, Nick J. Quinlan, Aaron R. Mychaleckyj, Josyf C. Farber, Emily Bonnie, Jessica K. Szpak, Michal Schofield, Ellen Achuthan, Premanand Guo, Hui Fortune, Mary D. Stevens, Helen Walker, Neil M. Ward, Lucas D. Kundaje, Anshul Kellis, Manolis Daly, Mark J. Barrett, Jeffrey C. Cooper, Jason D. Deloukas, Panos Todd, John A. Wallace, Chris Concannon, Patrick Rich, Stephen S. CA Type 1 Diabet Genetics Consortium TI Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SHARED CONTROLS; CELIAC-DISEASE; RISK; METAANALYSIS; EXPRESSION; CONSORTIUM; RESOURCE; MELLITUS; LINKAGE AB Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions(1,2), finding major pathways contributing to risk(3), with some loci shared across immune disorders(4-6). To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 x 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal. C1 [Onengut-Gumuscu, Suna; Chen, Wei-Min; Quinlan, Aaron R.; Mychaleckyj, Josyf C.; Farber, Emily; Bonnie, Jessica K.; Szpak, Michal; Concannon, Patrick; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA. [Onengut-Gumuscu, Suna] Univ Virginia, Dept Med, Div Endocrinol, Charlottesville, VA USA. [Chen, Wei-Min; Quinlan, Aaron R.; Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Burren, Oliver; Cooper, Nick J.; Schofield, Ellen; Achuthan, Premanand; Guo, Hui; Fortune, Mary D.; Stevens, Helen; Walker, Neil M.; Cooper, Jason D.; Todd, John A.; Wallace, Chris] Univ Cambridge, Natl Inst Hlth Res,Dept Med Genet, Biomed Res Ctr,Wellcome Trust Diabet & Inflammat, Cambridge Inst Med Res,Juvenile Diabet Res Fdn, Cambridge, England. [Ward, Lucas D.; Kundaje, Anshul; Kellis, Manolis] MIT, Dept Comp Sci, Cambridge, MA 02139 USA. [Ward, Lucas D.; Kundaje, Anshul; Kellis, Manolis; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Kundaje, Anshul] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Kundaje, Anshul; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Barrett, Jeffrey C.; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Wallace, Chris] Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England. RP Rich, SS (reprint author), Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA. EM ssr4n@virginia.edu RI de Bakker, Paul/B-8730-2009; Boehm, Bernhard/F-8750-2015; Todd, John/A-3542-2010; Tillmann, Vallo/G-8118-2012; Cameron, Fergus/N-9535-2015; Deloukas, Panos/B-2922-2013; Skrha, Jan/C-3095-2017; Argente, Jesus/L-2928-2013; OI de Bakker, Paul/0000-0001-7735-7858; Tillmann, Vallo/0000-0002-5279-4493; Deloukas, Panos/0000-0001-9251-070X; Skrha, Jan/0000-0001-8012-8802; Burren, Oliver/0000-0002-3388-5760; Ward, Lucas/0000-0002-8017-809X; Johannesen, Jesper/0000-0003-2772-2567; Schofield, Ellen/0000-0003-0648-1418; Plagnol, Vincent/0000-0002-5597-9215; Argente, Jesus/0000-0001-5826-0276; Avbelj Stefanija, Magdalena/0000-0002-0836-5114; Barrett, Jeffrey/0000-0002-1152-370X; McLaren, William/0000-0001-6218-1116; Walker, Neil/0000-0001-9796-7688; Wallace, Chris/0000-0001-9755-1703; Castano, Luis/0000-0003-0437-9401; Ludvigsson, Johnny/0000-0003-1695-5234 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); US National Institutes of Health [U01 DK062418]; NIDDK [DK046635, DK085678]; joint JDRF; Wellcome Trust [WT061858/09115, 089989]; NIHR Cambridge Biomedical Research Centre; Eli Lilly and Company; Wellcome Trust Strategic Award [100140]; UK Medical Research Council; Wellcome Trust award [076113] FX This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD) and JDRF and supported by grant U01 DK062418 from the US National Institutes of Health. Further support was provided by grants from the NIDDK (DK046635 and DK085678) to P.C. and by a joint JDRF and Wellcome Trust grant (WT061858/09115) to the Diabetes and Inflammation Laboratory at Cambridge University, which also received support from the NIHR Cambridge Biomedical Research Centre. ImmunoBase receives support from Eli Lilly and Company. C.W. and H.G. are funded by the Wellcome Trust (089989). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140).; We gratefully acknowledge the following groups and individuals who provided biological samples or data for this study. We obtained DNA samples from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council and the Wellcome Trust. We acknowledge use of DNA samples from the NIHR Cambridge BioResource. We thank volunteers for their support and participation in the Cambridge BioResource and members of the Cambridge BioResource Scientific Advisory Board (SAB) and Management Committee for their support of our study. We acknowledge the NIHR Cambridge Biomedical Research Centre for funding. Access to Cambridge BioResource volunteers and to their data and samples are governed by the Cambridge BioResource SAB. Documents describing access arrangements and contact details are available at http://www.cambridgebioresource.org.uk/. We thank the Avon Longitudinal Study of Parents and Children laboratory in Bristol, UK, and the British 1958 Birth Cohort team, including S. Ring, R. Jones, M. Pembrey, W. McArdle, D. Strachan and P. Burton, for preparing and providing the control DNA samples. This study makes use of data generated by the Wellcome Trust Case Control Consortium, funded by Wellcome Trust award 076113; a full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. NR 48 TC 69 Z9 69 U1 1 U2 28 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 APR PY 2015 VL 47 IS 4 BP 381 EP U199 DI 10.1038/ng.3245 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CE6CH UT WOS:000351922900014 PM 25751624 ER PT J AU Aung, T Ozaki, M Mizoguchi, T Allingham, RR Li, Z Haripriya, A Nakano, S Uebe, S Harder, JM Chan, ASY Lee, MC Burdon, KP Astakhov, YS Abu-Amero, KK Zenteno, JC Nilgun, Y Zarnowski, T Pakravan, M Abu Safieh, L Jia, LY Wang, YX Williams, S Paoli, D Schlottmann, PG Huang, LL Sim, KS Foo, JN Nakano, M Ikeda, Y Kumar, RS Ueno, M Manabe, SI Hayashi, K Kazama, S Ideta, R Mori, Y Miyata, K Sugiyama, K Higashide, T Chihara, E Inoue, K Ishiko, S Yoshida, A Yanagi, M Kiuchi, Y Aihara, M Ohashi, T Sakurai, T Sugimoto, T Chuman, H Matsuda, F Yamashiro, K Gotoh, N Miyake, M Astakhov, SY Osman, EA Al-Obeidan, SA Owaidhah, O Al-Jasim, L Al Shahwan, S Fogarty, RA Leo, P Yetkin, Y Oguz, C Kanavi, MR Beni, AN Yazdani, S Akopov, EL Toh, KY Howell, GR Orr, AC Goh, Y Meah, WY Peh, SQ Kosior-Jarecka, E Lukasik, U Krumbiegel, M Vithana, EN Wong, TY Liu, YT Koch, AEA Challa, P Rautenbach, RM Mackey, DA Hewitt, AW Mitchell, P Wang, JJ Ziskind, A Carmichael, T Ramakrishnan, R Narendran, K Venkatesh, R Vijayan, S Zhao, PQ Chen, XY Guadarrama-Vallejo, D Cheng, CY Perera, SA Husain, R Ho, SL Welge-Luessen, UC Mardin, C Schloetzer-Schrehardt, U Hillmer, AM Herms, S Moebus, S Nothen, MM Weisschuh, N Shetty, R Ghosh, A Teo, YY Brown, MA Lischinsky, I Crowston, JG Coote, M Zhao, BW Sang, JH Zhang, NH You, QS Vysochinskaya, V Founti, P Chatzikyriakidou, A Lambropoulos, A Anastasopoulos, E Coleman, AL Wilson, MR Rhee, DJ Kang, JH May-Bolchakova, I Heegaard, S Mori, K Alward, WLM Jonas, JB Xu, L Liebmann, JM Chowbay, B Schaeffeler, E Schwab, M Lerner, F Wang, NL Yang, ZL Frezzotti, P Kinoshita, S Fingert, JH Inatani, M Tashiro, K Reis, A Edward, DP Pasquale, LR Kubota, T Wiggs, JL Pasutto, F Topouzis, F Dubina, M Craig, JE Yoshimura, N Sundaresan, P John, SWM Ritch, R Hauser, MA Khor, CC AF Aung, Tin Ozaki, Mineo Mizoguchi, Takanori Allingham, R. Rand Li, Zheng Haripriya, Aravind Nakano, Satoko Uebe, Steffen Harder, Jeffrey M. Chan, Anita S. Y. Lee, Mei Chin Burdon, Kathryn P. Astakhov, Yury S. Abu-Amero, Khaled K. Zenteno, Juan C. Nilguen, Yildirim Zarnowski, Tomasz Pakravan, Mohammad Abu Safieh, Leen Jia, Liyun Wang, Ya Xing Williams, Susan Paoli, Daniela Schlottmann, Patricio G. Huang, Lulin Sim, Kar Seng Foo, Jia Nee Nakano, Masakazu Ikeda, Yoko Kumar, Rajesh S. Ueno, Morio Manabe, Shin-Ichi Hayashi, Ken Kazama, Shigeyasu Ideta, Ryuichi Mori, Yosai Miyata, Kazunori Sugiyama, Kazuhisa Higashide, Tomomi Chihara, Etsuo Inoue, Kenji Ishiko, Satoshi Yoshida, Akitoshi Yanagi, Masahide Kiuchi, Yoshiaki Aihara, Makoto Ohashi, Tsutomu Sakurai, Toshiya Sugimoto, Takako Chuman, Hideki Matsuda, Fumihiko Yamashiro, Kenji Gotoh, Norimoto Miyake, Masahiro Astakhov, Sergei Y. Osman, Essam A. Al-Obeidan, Saleh A. Owaidhah, Ohoud Al-Jasim, Leyla Al Shahwan, Sami Fogarty, Rhys A. Leo, Paul Yetkin, Yaz Oguz, Cilingir Kanavi, Mozhgan Rezaei Beni, Afsaneh Nederi Yazdani, Shahin Akopov, Evgeny L. Toh, Kai-Yee Howell, Gareth R. Orr, Andrew C. Goh, Yufen Meah, Wee Yang Peh, Su Qin Kosior-Jarecka, Ewa Lukasik, Urszula Krumbiegel, Mandy Vithana, Eranga N. Wong, Tien Yin Liu, Yutao Koch, Allison E. Ashley Challa, Pratap Rautenbach, Robyn M. Mackey, David A. Hewitt, Alex W. Mitchell, Paul Wang, Jie Jin Ziskind, Ari Carmichael, Trevor Ramakrishnan, Rangappa Narendran, Kalpana Venkatesh, Rangaraj Vijayan, Saravanan Zhao, Peiquan Chen, Xueyi Guadarrama-Vallejo, Dalia Cheng, Ching Yu Perera, Shamira A. Husain, Rahat Ho, Su-Ling Welge-Luessen, Ulrich-Christoph Mardin, Christian Schloetzer-Schrehardt, Ursula Hillmer, Axel M. Herms, Stefan Moebus, Susanne Noethen, Markus M. Weisschuh, Nicole Shetty, Rohit Ghosh, Arkasubhra Teo, Yik Ying Brown, Matthew A. Lischinsky, Ignacio Crowston, Jonathan G. Coote, Michael Zhao, Bowen Sang, Jinghong Zhang, Nihong You, Qisheng Vysochinskaya, Vera Founti, Panayiota Chatzikyriakidou, Anthoula Lambropoulos, Alexandros Anastasopoulos, Eleftherios Coleman, Anne L. Wilson, M. Roy Rhee, Douglas J. Kang, Jae Hee May-Bolchakova, Inna Heegaard, Steffen Mori, Kazuhiko Alward, Wallace L. M. Jonas, Jost B. Xu, Liang Liebmann, Jeffrey M. Chowbay, Balram Schaeffeler, Elke Schwab, Matthias Lerner, Fabian Wang, Ningli Yang, Zhenglin Frezzotti, Paolo Kinoshita, Shigeru Fingert, John H. Inatani, Masaru Tashiro, Kei Reis, Andre Edward, Deepak P. Pasquale, Louis R. Kubota, Toshiaki Wiggs, Janey L. Pasutto, Francesca Topouzis, Fotis Dubina, Michael Craig, Jamie E. Yoshimura, Nagahisa Sundaresan, Periasamy John, Simon W. M. Ritch, Robert Hauser, Michael A. Khor, Chiea-Chuen CA Blue Mountains Eye Study GWAS Team Wellcome Trust Case Control Consor TI A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome SO NATURE GENETICS LA English DT Article ID LOXL1 GENE POLYMORPHISMS; PSEUDOEXFOLIATION SYNDROME; SEQUENCE VARIANTS; JAPANESE POPULATION; UNITED-STATES; GLAUCOMA; DISEASE; GERMAN AB Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 x 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: ORA allele = 9.87, P = 2.13 x 10(-217); non-Japanese: ORA allele = 0.49, P = 2.35 x 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease. C1 [Aung, Tin; Chan, Anita S. Y.; Lee, Mei Chin; Vithana, Eranga N.; Wong, Tien Yin; Cheng, Ching Yu; Perera, Shamira A.; Husain, Rahat; Ghosh, Arkasubhra; Khor, Chiea-Chuen] Singapore Eye Res Inst, Singapore, Singapore. [Aung, Tin; Chan, Anita S. Y.; Wong, Tien Yin; Perera, Shamira A.; Husain, Rahat] Singapore Natl Eye Ctr, Singapore, Singapore. [Aung, Tin; Wong, Tien Yin; Cheng, Ching Yu; Khor, Chiea-Chuen] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore. [Aung, Tin; Li, Zheng; Sim, Kar Seng; Foo, Jia Nee; Toh, Kai-Yee; Goh, Yufen; Meah, Wee Yang; Peh, Su Qin; Khor, Chiea-Chuen] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Aung, Tin] Natl Univ Singapore, Duke Univ, Grad Sch Med, Singapore 117548, Singapore. [Ozaki, Mineo] Ozaki Eye Hosp, Hyuga, Japan. [Ozaki, Mineo; Manabe, Shin-Ichi; Hayashi, Ken] Hayashi Eye Hosp, Fukuoka, Japan. [Mizoguchi, Takanori] Mizoguchi Eye Hosp, Sasebo, Japan. [Allingham, R. Rand; Challa, Pratap; Teo, Yik Ying; Hauser, Michael A.] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA. [Haripriya, Aravind; Ramakrishnan, Rangappa; Narendran, Kalpana; Venkatesh, Rangaraj] Aravind Eye Hosp, Intraocular Lens & Cataract Clin, Madurai, Tamil Nadu, India. [Nakano, Satoko; Kubota, Toshiaki] Oita Univ, Fac Med, Dept Ophthalmol, Oita 87011, Japan. [Uebe, Steffen; Krumbiegel, Mandy; Reis, Andre; Pasutto, Francesca] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Harder, Jeffrey M.; Howell, Gareth R.; John, Simon W. M.] Jackson Lab, Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. [Burdon, Kathryn P.; Fogarty, Rhys A.; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. [Burdon, Kathryn P.; Hewitt, Alex W.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia. [Astakhov, Yury S.; Astakhov, Sergei Y.; Akopov, Evgeny L.; Dubina, Michael] First Pavlov State Med Univ St Petersburg, Dept Ophthalmol, St Petersburg, Russia. [Abu-Amero, Khaled K.; Osman, Essam A.; Al-Obeidan, Saleh A.] King Saud Univ, Coll Med, Dept Ophthalmol, Riyadh 11461, Saudi Arabia. [Abu-Amero, Khaled K.] Univ Florida, Coll Med, Dept Ophthalmol, Jacksonville, FL USA. [Zenteno, Juan C.; Guadarrama-Vallejo, Dalia] Inst Ophthalmol Conde de Valenciana, Dept Genet, Mexico City, DF, Mexico. [Zenteno, Juan C.; Guadarrama-Vallejo, Dalia] Univ Nacl Autonoma Mexico, Fac Med, Dept Biochem, Mexico City 04510, DF, Mexico. [Nilguen, Yildirim; Yetkin, Yaz; Oguz, Cilingir] Eskisehir Osmangazi Univ, Dept Ophthalmol, Meselik, Turkey. [Zarnowski, Tomasz; Kosior-Jarecka, Ewa; Lukasik, Urszula] Med Univ Lublin, Dept Diagnost & Microsurg Glaucoma, Lublin, Poland. [Pakravan, Mohammad; Owaidhah, Ohoud; Al-Jasim, Leyla; Al Shahwan, Sami; Kanavi, Mozhgan Rezaei; Beni, Afsaneh Nederi; Yazdani, Shahin] Shahid Beheshti Univ Med Sci, Labbafinejad Med Ctr, Ophthalm Res Ctr, Dept Ophthalmol, Tehran, Iran. [Abu Safieh, Leen; Zhao, Bowen; Edward, Deepak P.] King Khalid Eye Specialist Hosp, Riyadh 11462, Saudi Arabia. [Jia, Liyun; Sang, Jinghong; Zhang, Nihong; Wang, Ningli] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China. [Wang, Ya Xing; You, Qisheng; Xu, Liang] Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing, Peoples R China. [Williams, Susan; Carmichael, Trevor] Univ Witwatersrand, Dept Neurosci, Div Ophthalmol, Johannesburg, South Africa. [Paoli, Daniela] Monfalcone Hosp, Dept Ophthalmol, Gorizia, Italy. [Schlottmann, Patricio G.] Org Med Invest, Buenos Aires, DF, Argentina. [Huang, Lulin; Yang, Zhenglin] Hosp Univ Elect Sci & Technol China, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu, Peoples R China. [Huang, Lulin; Yang, Zhenglin] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China. [Huang, Lulin; Yang, Zhenglin] Univ Elect Sci & Technol China, Sch Med, Chengdu 610054, Peoples R China. [Huang, Lulin; Yang, Zhenglin] Chinese Acad Sci, Sichuan Translat Med Hosp, Chengdu, Peoples R China. [Nakano, Masakazu; Mori, Kazuhiko; Tashiro, Kei] Kyoto Prefectural Univ Med, Dept Genom Med Sci, Kyoto, Japan. [Ikeda, Yoko; Ueno, Morio; Kinoshita, Shigeru] Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan. [Kumar, Rajesh S.; Shetty, Rohit] Narayana Nethralaya Eye Hosp, Glaucoma Serv, Bangalore, Karnataka, India. [Kazama, Shigeyasu] Shinjo Eye Clin, Miyazaki, Japan. [Ideta, Ryuichi] Ideta Eye Hosp, Kumamoto, Japan. [Mori, Yosai; Miyata, Kazunori] Miyata Eye Hosp, Miyazaki, Japan. [Miyata, Kazunori; Sugimoto, Takako; Chuman, Hideki] Miyazaki Univ, Fac Med, Dept Ophthalmol, Miyazaki, Japan. [Sugiyama, Kazuhisa; Higashide, Tomomi] Kanazawa Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Kanazawa, Ishikawa, Japan. [Chihara, Etsuo] Sensho Kai Eye Inst, Kyoto, Japan. [Inoue, Kenji] Inouye Eye Hosp, Tokyo, Japan. [Ishiko, Satoshi] Asahikawa Med Univ, Dept Med, Asahikawa, Hokkaido, Japan. [Ishiko, Satoshi] Asahikawa Med Univ, Engn Combined Res Inst, Asahikawa, Hokkaido, Japan. [Yoshida, Akitoshi] Asahikawa Med Univ, Dept Ophthalmol, Asahikawa, Hokkaido, Japan. [Yanagi, Masahide; Kiuchi, Yoshiaki] Hiroshima Univ, Dept Ophthalmol & Visual Sci, Hiroshima, Japan. [Aihara, Makoto] Yotsuya Shirato Eye Clin, Tokyo, Japan. [Ohashi, Tsutomu] Ohashi Eye Ctr, Sapporo, Hokkaido, Japan. [Sakurai, Toshiya] Tane Mem Eye Hosp, Osaka, Japan. [Matsuda, Fumihiko; Miyake, Masahiro] Kyoto Univ, Grad Sch Med, INSERM, Ctr Genom Med,U852, Kyoto, Japan. [Yamashiro, Kenji; Gotoh, Norimoto; Miyake, Masahiro; Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan. [Leo, Paul] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Translat Res Inst, Brisbane, Qld, Australia. [Orr, Andrew C.] Dalhousie Univ, Dept Ophthalmol & Visual Sci, Halifax, NS, Canada. [Liu, Yutao; Koch, Allison E. Ashley; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Liu, Yutao] Georgia Regents Univ, Dept Cellular Biol & Anat, Augusta, GA USA. [Rautenbach, Robyn M.; Ziskind, Ari] Univ Stellenbosch, Fac Med & Hlth Sci, Div Ophthalmol, Cape Town, South Africa. [Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia. [Hewitt, Alex W.; Crowston, Jonathan G.; Coote, Michael] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Vijayan, Saravanan; Sundaresan, Periasamy] Aravind Med Res Fdn, Dept Genet, Madurai, Tamil Nadu, India. [Zhao, Peiquan] Shanghai Jiao Tong Univ, Dept Ophthalmol, Xin Hua Hosp, Sch Med, Shanghai 200030, Peoples R China. [Chen, Xueyi; Brown, Matthew A.] Xinjiang Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Urumqi, Xinjiang Uygur, Peoples R China. [Ho, Su-Ling] Tan Tock Seng Hosp, Natl Healthcare Grp Eye Inst, Singapore, Singapore. [Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Schloetzer-Schrehardt, Ursula] Univ Erlangen Nurnberg, Dept Ophthalmol, Erlangen, Germany. [Hillmer, Axel M.] Genome Inst Singapore, Canc Therapeut & Stratified Oncol, Singapore, Singapore. [Herms, Stefan; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Herms, Stefan; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Herms, Stefan] Univ Basel Hosp, Div Med Genet, CH-4031 Basel, Switzerland. [Herms, Stefan] Univ Basel, Dept Biomed, Human Genet Res Grp, Basel, Switzerland. [Moebus, Susanne] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Weisschuh, Nicole] Dept Ophthalmol, Inst Ophthalm Res, Tubingen, Germany. [Ghosh, Arkasubhra] Narayana Nethralaya Fdn, Genes Repair & Regenerat Ophthalm Workstat Res La, Bangalore, Karnataka, India. [Teo, Yik Ying] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Lischinsky, Ignacio] Ctr Oftalmol Lischinsky, San Miguel De Tucuman, Argentina. [Crowston, Jonathan G.; Coote, Michael] Univ Melbourne, Dept Ophthalmol, Melbourne, Vic, Australia. [Vysochinskaya, Vera; Dubina, Michael] St Petersburg Acad Univ, St Petersburg, Russia. [Founti, Panayiota; Anastasopoulos, Eleftherios; Topouzis, Fotis] Aristotle Univ Thessaloniki, Fac Med, Dept Ophthalmol, Amer Hellen Educ Progress Assoc Hosp, GR-54006 Thessaloniki, Greece. [Chatzikyriakidou, Anthoula; Lambropoulos, Alexandros] Aristotle Univ Thessaloniki, Fac Med, Dept Biol & Genet, GR-54006 Thessaloniki, Greece. [Coleman, Anne L.] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Ctr Commun Outreach & Policy, Los Angeles, CA 90095 USA. [Wilson, M. Roy] Wayne State Univ, Detroit, MI USA. [Rhee, Douglas J.; Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kang, Jae Hee; Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [May-Bolchakova, Inna] Mil Hosp Begin, Dept Ophthalmol, Paris, France. [Heegaard, Steffen] Univ Copenhagen, Dept Neurosci & Pharmacol, Eye Pathol Inst, Copenhagen, Denmark. [Heegaard, Steffen] Glostrup Univ Hosp, Dept Ophthalmol, Glostrup, Denmark. [Alward, Wallace L. M.; Fingert, John H.] Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA USA. [Alward, Wallace L. M.; Fingert, John H.] Univ Iowa, Dept Ophthalmol & Visual Sci, Carver Coll Med, Iowa City, IA USA. [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Heidelberg, Germany. [Liebmann, Jeffrey M.] NYU, Sch Med, Manhattan Eye Ear & Throat Hosp, New York, NY USA. [Chowbay, Balram] Natl Canc Ctr, Humphrey Oei Inst Canc Res, Div Med Sci, Singapore, Singapore. [Schaeffeler, Elke; Schwab, Matthias] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Schwab, Matthias] Univ Tubingen Hosp, Dept Clin Pharmacol, Tubingen, Germany. [Schwab, Matthias] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Lerner, Fabian] Fdn Estudio Glaucoma, Buenos Aires, DF, Argentina. [Frezzotti, Paolo] Univ Siena, Dept Surg, Sect Ophthalmol, I-53100 Siena, Italy. [Inatani, Masaru] Univ Fukui, Fac Med Sci, Dept Ophthalmol, Fukui 910, Japan. [Edward, Deepak P.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Ritch, Robert] New York Eye & Ear Infirm Mt Sinai, Einhorn Clin Res Ctr, New York, NY USA. RP Aung, T (reprint author), Singapore Eye Res Inst, Singapore, Singapore. EM aung_tin@yahoo.co.uk; khorcc@gis.a-star.edu.sg RI wang, YA XING/K-9671-2016; Deloukas, Panos/B-2922-2013; Reis, Andre/D-2309-2009; Blackwell, Jenefer/H-3015-2015; Jankowski, Janusz/H-2706-2012; Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Hewitt, Alex/D-1936-2013; Foo, Jia Nee/D-6069-2014; Hillmer, Axel/N-2927-2014 OI Sim, Kar Seng/0000-0002-3822-7759; Plomin, Robert/0000-0002-0756-3629; Nothen, Markus/0000-0002-8770-2464; Perera, Shamira/0000-0002-1404-5096; Khor, Chiea Chuen/0000-0002-1128-4729; Mackey, David/0000-0001-7914-4709; wang, YA XING/0000-0003-2749-7793; Deloukas, Panos/0000-0001-9251-070X; Reis, Andre/0000-0002-6301-6363; Ghosh, Arkasubhra/0000-0002-6570-5891; Jankowski, Janusz/0000-0003-2130-9181; Wang, Jie Jin/0000-0001-9491-4898; Hewitt, Alex/0000-0002-5123-5999; Foo, Jia Nee/0000-0001-9899-2308; Li , Zheng/0000-0002-7060-2213; Hillmer, Axel/0000-0002-3381-7266 FU Biomedical Research Council; Agency for Science, Technology and Research, Singapore; US National Institutes of Health/National Eye Institute grants [NIH/NEI R01 EY020928, NIH/NEI P30 EY014104]; US National Institutes of Health/National Eye Institute [EY11721, EY023512, EY018825]; Harvard Medical School Distinguished Ophthalmology Scholar Award; Harvard Glaucoma Center of Excellence; National Natural Science Foundation of China [81025006, 81170883]; Department of Science and Technology of Sichuan Province, China [2012SZ0219, 2011jtd0020]; Robert Bosch Stiftung (Stuttgart, Germany); German Cancer Consortium (DKTK), Germany; Ophthalmic Research Institute of Australia; National Health and Medical Research Council (NHMRC) [535044]; European Union (European Social Fund); Greek national funds under act 'Aristia' of the operational program 'Education and Lifelong Learning'; Australian NHMRC Canberra, Australia; NHMRC project [512423, 475604, 529912]; Wellcome Trust, UK, Wellcome Trust Case Control Consortium 2; [085475/B/08/Z]; [085475/08/Z] FX The authors thank the staff and participants of all studies for their important contributions. We thank K.-K. Heng, X.-Y. Chen, H.-M. Soo, S.-Q. Mok, A. Jamuth, N. Foxworth and M. Elbl for technical assistance. This research was funded by the Biomedical Research Council, Agency for Science, Technology and Research, Singapore. J.L.W. acknowledges support from US National Institutes of Health/National Eye Institute grants (NIH/NEI R01 EY020928 and NIH/NEI P30 EY014104). S.W.M.J. acknowledges support from grant EY11721 from the US National Institutes of Health/National Eye Institute and is an investigator of the Howard Hughes Medical Institute. L.R.P. acknowledges support from a Harvard Medical School Distinguished Ophthalmology Scholar Award and the Harvard Glaucoma Center of Excellence. J.H.F. acknowledges support from US National Institutes of Health/National Eye Institute grants (EY023512 and EY018825). Z.Y. acknowledges support from the National Natural Science Foundation of China (81025006 and 81170883), as well as from the Department of Science and Technology of Sichuan Province, China (2012SZ0219 and 2011jtd0020). M.S. acknowledges support from Robert Bosch Stiftung (Stuttgart, Germany) and the German Cancer Consortium (DKTK), Germany. The Australian case cohort was funded by grants from the Ophthalmic Research Institute of Australia and National Health and Medical Research Council (NHMRC) project 535044. The Thessaloniki Eye Study was cofunded by the European Union (European Social Fund) and Greek national funds under act 'Aristia' of the operational program 'Education and Lifelong Learning' (Supplementary Note). Blue Mountains Eye Study (BMES) GWAS and genotyping costs were supported by the Australian NHMRC Canberra, Australia; NHMRC project grants 512423, 475604 and 529912) and the Wellcome Trust, UK, as part of the Wellcome Trust Case Control Consortium 2 (A. Viswanathan, P. McGuffin, P. Mitchell, F. Topouzis, P. Foster; grants 085475/B/08/Z and 085475/08/Z). K.P.B. is an NHMRC Senior Research Fellow, and J.E.C. is an NHMRC Practitioner Fellow. M.A.B. is an NHMRC Principal Research Fellow. A.W.H. is an NHMRC Peter Doherty Fellow. NR 34 TC 11 Z9 11 U1 5 U2 21 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 APR PY 2015 VL 47 IS 4 BP 387 EP U145 DI 10.1038/ng.3226 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CE6CH UT WOS:000351922900015 PM 25706626 ER PT J AU Chavez, A Scheiman, J Vora, S Pruitt, BW Tuttle, M Iyer, EPR Lin, SL Kiani, S Guzman, CD Wiegand, DJ Ter-Ovanesyan, D Braff, JL Davidsohn, N Housden, BE Perrimon, N Weiss, R Aach, J Collins, JJ Church, GM AF Chavez, Alejandro Scheiman, Jonathan Vora, Suhani Pruitt, Benjamin W. Tuttle, Marcelle Iyer, Eswar P. R. Lin, Shuailiang Kiani, Samira Guzman, Christopher D. Wiegand, Daniel J. Ter-Ovanesyan, Dmitry Braff, Jonathan L. Davidsohn, Noah Housden, Benjamin E. Perrimon, Norbert Weiss, Ron Aach, John Collins, James J. Church, George M. TI Highly efficient Cas9-mediated transcriptional programming SO NATURE METHODS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; STEM-CELLS; ACTIVATION; SYSTEM; CAS9; COMPLEX; CRISPR-CAS9; IMMUNITY; DNA AB The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs). C1 [Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; Pruitt, Benjamin W.; Tuttle, Marcelle; Iyer, Eswar P. R.; Guzman, Christopher D.; Wiegand, Daniel J.; Ter-Ovanesyan, Dmitry; Braff, Jonathan L.; Davidsohn, Noah; Collins, James J.; Church, George M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Chavez, Alejandro] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; Iyer, Eswar P. R.; Lin, Shuailiang; Ter-Ovanesyan, Dmitry; Davidsohn, Noah; Housden, Benjamin E.; Perrimon, Norbert; Aach, John; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Kiani, Samira; Weiss, Ron] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Lin, Shuailiang; Housden, Benjamin E.; Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Lin, Shuailiang] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. [Kiani, Samira; Weiss, Ron; Collins, James J.] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA. [Weiss, Ron] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Collins, James J.] MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA. [Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Church, GM (reprint author), Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. EM gchurch@genetics.med.harvard.edu RI Lin, Shuailiang/O-3272-2016; Iyer, Eswar/E-8443-2017; OI Pruitt, Benjamin/0000-0001-7532-7081; Housden, Benjamin/0000-0001-9134-4279 FU US Department of Energy [DE-FG02-02ER63445]; Wyss Institute for Biologically Inspired Engineering; National Cancer Institute [5T32CA009216-34]; National Science Foundation Graduate Research Fellowship Program; Department of Biological Engineering at the Massachusetts Institute of Technology; Department of Genetics at Harvard Medical School FX We thank K. Esvelt, P. Mali and the rest of the members of the Church and Collins labs for helpful discussions. We thank T. Ferrante, S. Byrne and M. Farrell for technical assistance, A. Keung (Massachusetts Institute of Technology) for providing zinc-finger reporter constructs, and J. Schulak for graphic design. This work was supported by US National Institutes of Health National Human Genome Research Institute grant P50 HG005550, US Department of Energy grant DE-FG02-02ER63445 and the Wyss Institute for Biologically Inspired Engineering. A.C. acknowledges funding by the National Cancer Institute grant 5T32CA009216-34. S.V. acknowledges funding by the National Science Foundation Graduate Research Fellowship Program, the Department of Biological Engineering at the Massachusetts Institute of Technology and the Department of Genetics at Harvard Medical School. NR 22 TC 88 Z9 89 U1 24 U2 92 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD APR PY 2015 VL 12 IS 4 BP 326 EP U65 DI 10.1038/NMETH.3312 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CE8HR UT WOS:000352083100018 PM 25730490 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Epidemiology and risk factors for IBD SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; VITAMIN-D-RECEPTOR; EUROPEAN PROSPECTIVE COHORT; PEDIATRIC CROHNS-DISEASE; POPULATION-BASED COHORT; LONG-TERM INTAKE; ULCERATIVE-COLITIS; CIGARETTE-SMOKING; PSYCHOLOGICAL STRESS; NATURAL-HISTORY AB IBD, comprising Crohn's disease and ulcerative colitis, is a chronic immunologically mediated disease at the intersection of complex interactions between genetics, environment and gut microbiota. Established high-prevalence populations of IBD in North America and Europe experienced the steepest increase in incidence towards the second half of the twentieth century. Furthermore, populations previously considered 'low risk' (such as in Japan and India) are witnessing an increase in incidence. Potentially relevant environmental influences span the spectrum of life from mode of childbirth and early-life exposures (including breastfeeding and antibiotic exposure in infancy) to exposures later on in adulthood (including smoking, major life stressors, diet and lifestyle). Data support an association between smoking and Crohn's disease whereas smoking cessation, but not current smoking, is associated with an increased risk of ulcerative colitis. Dietary fibre (particularly fruits and vegetables), saturated fats, depression and impaired sleep, and low vitamin D levels have all been associated with incident IBD. Interventional studies assessing the effects of modifying these risk factors on natural history and patient outcomes are an important unmet need. In this Review, the changing epidemiology of IBD, mechanisms behind various environmental associations and interventional studies to modify risk factors and disease course are discussed. C1 Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU US National Institutes of Health [K23 DKO97142] FX A.N.A. is supported by funding from the US National Institutes of Health (K23 DKO97142). NR 203 TC 82 Z9 84 U1 20 U2 61 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 EI 1759-5053 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD APR PY 2015 VL 12 IS 4 BP 205 EP 217 DI 10.1038/nrgastro.2015.34 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE9XG UT WOS:000352196200005 PM 25732745 ER PT J AU Jimeno, A Bauman, JE Weissman, C Adkins, D Schnadig, I Beauregard, P Bowles, DW Spira, A Levy, B Seetharamu, N Hausman, D Walker, L Rudin, CM Shirai, K AF Jimeno, Antonio Bauman, Julie E. Weissman, Charles Adkins, Douglas Schnadig, Ian Beauregard, Patrice Bowles, Daniel W. Spira, Alexander Levy, Benjamin Seetharamu, Nagashree Hausman, Diana Walker, Luke Rudin, Charles M. Shirai, Keisuke TI A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer SO ORAL ONCOLOGY LA English DT Article DE PIK3CA; PI3K; Docetaxel; Head and neck squamous cell cancer ID ADVANCED SOLID TUMORS; I PI3K INHIBITOR; LUNG-CANCER; PIK3CA GENE; MUTATIONS; CARCINOMA; PATHWAY; DRUG AB Introduction: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is frequently altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory HNSCC. Methods: Patients with locally advanced, recurrent or metastatic HNSCC who had received at least one and no more than two prior systemic treatment regimens were randomized (1: 1) to a combination of docetaxel (75 mg/m(2) IV every 21 days) with or without PX-866 (8 mg PO daily; Arms A and B, respectively). The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (RR), overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes. Results: 85 patients were enrolled. There was a non-significant improvement in response rate in the combination arm (14% vs. 5%; P = 0.13). Median PFS was 92 days in Arm A and 82 days in Arm B (P = 0.42). There was no difference in OS between the two arms (263 vs. 195 days; P = 0.62). Grade 3 or higher adverse events were infrequent, but more common in the combination arm with respect to diarrhea (17% vs. 2%), nausea (7% vs. 0%), and febrile neutropenia (21% vs. 5%); grade 3 or higher anemia was more frequent in arm B (7% vs. 27%). PIK3CA mutations or PTEN loss were infrequently observed. Conclusion: The addition of PX-866 to docetaxel did not improve PFS, RR, or OS in patients with advanced, refractory HNSCC without molecular pre-selection. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Jimeno, Antonio; Bowles, Daniel W.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Bauman, Julie E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Weissman, Charles] New York Hematol, New York, NY USA. [Adkins, Douglas] Washington Univ, St Louis, MO USA. [Schnadig, Ian] Compass Oncol, Tualatin, OR USA. [Schnadig, Ian; Spira, Alexander] US Oncol Res, The Woodlands, TX USA. [Beauregard, Patrice] CHUS Hop Fleurimont, Quebec City, PQ, Canada. [Bowles, Daniel W.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Spira, Alexander] Virginia Canc Specialists, Fairfax, VA USA. [Levy, Benjamin] St Lukes Hosp, Beth Israel Hosp, Mt Sinai Hlth Syst, New York, NY USA. [Seetharamu, Nagashree] NYU, New York, NY USA. [Hausman, Diana; Walker, Luke] Oncothyreon Inc, Seattle, WA USA. [Rudin, Charles M.] Johns Hopkins Univ, Baltimore, MD USA. [Shirai, Keisuke] Med Univ S Carolina, Charleston, SC 29425 USA. RP Jimeno, A (reprint author), Univ Colorado, Sch Med, Div Med Oncol, 12801 East 17th Ave,MS8117, Aurora, CO 80045 USA. EM antonio.jimeno@ucdenver.edu FU Oncothyreon Inc. FX This clinical trial was sponsored by Oncothyreon Inc. No funding was received from the NIH, Wellcome Trust or HHMI. NR 33 TC 13 Z9 13 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2015 VL 51 IS 4 BP 383 EP 388 DI 10.1016/j.oraloncology.2014.12.013 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA CE7JX UT WOS:000352016600014 PM 25593016 ER PT J AU Selzman, KA Banks, T Bodtcher, R Keung, E AF Selzman, Kimberly A. Banks, Thomas Bodtcher, Roy Keung, Edmond TI Pacemakers at the Elective Replacement Indicator with a Normal Magnet Rate on Transtelephonic Monitoring SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE pacemaker; transtelephonic; elective replacement indicator; ERI; magnet rate; battery voltage C1 [Selzman, Kimberly A.; Banks, Thomas; Bodtcher, Roy] Vet Affairs Med Ctr, George E Wahlen Dept, Div Cardiol, Salt Lake City, UT 84148 USA. [Selzman, Kimberly A.] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT USA. [Keung, Edmond] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. RP Selzman, KA (reprint author), Vet Affairs Med Ctr, George E Wahlen Dept, Div Cardiol, VA 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM kimberly.selzman@va.gov NR 3 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD APR PY 2015 VL 38 IS 4 BP 522 EP 525 DI 10.1111/pace.12415 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA CF1FB UT WOS:000352288100017 PM 24787276 ER PT J AU Widger, K Bouffet, E Friedrichsdorf, S Greenberg, M Husain, A Liben, S Pole, JD Siden, H Whitlock, J Wolfe, J Rapoport, A AF Widger, Kimberley Bouffet, Eric Friedrichsdorf, Stefan Greenberg, Mark Husain, Amna Liben, Stephen Pole, Jason D. Siden, Harold Whitlock, James Wolfe, Joanne Rapoport, Adam TI Enhancing the quality of palliative care for children with cancer: A nation-wide train-the-trainer educational initiative SO PAEDIATRICS & CHILD HEALTH LA English DT Editorial Material ID LIFE AB It is now widely endorsed that palliative care (PC) principles should be integrated into the routine care of all children diagnosed with cancer, not only those at end of life (1). However, paediatric health professionals report receiving little training in PC (2), and bereaved parents continue to report suboptimal care throughout the disease course (3,4). It is crucial that all health professionals caring for children with cancer receive comprehensive education about evidence-based PC and support to implement new knowledge. To achieve these goals, we will implement a national 'roll-out' of Education in Palliative and End-of-Life Care for Pediatrics (EPEC (R)-Pediatrics), using a 'train-the-trainer' model. C1 [Widger, Kimberley] Univ Toronto, Lawrence S Bloomberg Fac Nursing, Toronto, ON M5T 1P8, Canada. [Bouffet, Eric; Whitlock, James] Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada. [Friedrichsdorf, Stefan] Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, Minneapolis, MN USA. [Greenberg, Mark; Pole, Jason D.] Pediat Oncol Grp Ontario, Toronto, ON, Canada. [Husain, Amna] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Husain, Amna] Mt Sinai Hosp, Temmy Latner Ctr Palliat Care, Toronto, ON M5G 1X5, Canada. [Liben, Stephen] Montreal Childrens Hosp, Pediat Palliat Care Program, Montreal, PQ H3H 1P3, Canada. [Siden, Harold] Univ British Columbia, Dept Pediat, Vancouver, BC V6T 1W5, Canada. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Rapoport, Adam] Hosp Sick Children, Paediat Adv Care Team, Toronto, ON M5G 1X8, Canada. RP Widger, K (reprint author), Univ Toronto, Lawrence S Bloomberg Fac Nursing, 155 Coll St,Suite 120, Toronto, ON M5T 1P8, Canada. EM kim.widger@utoronto.ca NR 4 TC 1 Z9 1 U1 2 U2 5 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 1205-7088 J9 PAED CHILD HEALT-CAN JI Paediatr. Child Health PD APR PY 2015 VL 20 IS 3 BP 157 EP 158 PG 2 WC Pediatrics SC Pediatrics GA CF4BT UT WOS:000352494200012 ER PT J AU Simmonds, MJ Finley, EP Vale, S Pugh, MJ Turner, BJ AF Simmonds, Maureen J. Finley, Erin P. Vale, Shruthi Pugh, Mary Jo Turner, Barbara J. TI A Qualitative Study of Veterans on Long-Term Opioid Analgesics: Barriers and Facilitators to Multimodality Pain Management SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Alternative Therapies; Narcotics; Veterans ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; PLANNED BEHAVIOR; RANDOMIZED-TRIAL; THERAPY; GUIDELINES; OVERDOSE; SUPPORT; HEALTH AB ObjectiveThe aim of this study was to examine barriers and facilitators to multimodality chronic pain care among veterans on high-dose opioid analgesics for chronic non-cancer pain. SettingA Veterans Health Administration clinic in San Antonio. ParticipantsTwenty-five veterans taking at least 50mg morphine equivalent daily oral opioid doses for more than 6months. MethodsThree semi-structured focus groups, each with seven to nine veterans. Interview guide addressed: chronic pain effects on quality of life, attitudes/experiences with multimodality pain care, social support, and interest in peer support. In an iterative process using grounded theory, three reviewers reviewed de-identified transcripts for themes. The theory of planned behavior (TPB) framework was used to classify barriers and facilitators to multimodal pain management. Main ResultsThe 25 participants had a mean age of 54years (39-70); 32% were women and 24% non-white. The three TPB dimensions (attitudes, social norms, and perceived behavioral control) were reflected in emergent themes: 1) uncontrollable impact of pain in all aspects of life; 2) reliance on opioids and challenges in obtaining these drugs despite ambivalence about benefits; 3) poor access to and beliefs about non-pharmacologic therapies; 4) frustrations with Department of Veterans Affairs health care; and 5) poor social support and isolation reflected by limited interest in peer support. ConclusionsVeterans with chronic pain on long-term opioids hold pervasive attitudes that prevent them from using multimodality pain management options, lack social support and social norms for non-opioid-based pain treatment options, and have poor perceived control due to poor access to multimodality care. C1 [Simmonds, Maureen J.; Finley, Erin P.; Vale, Shruthi; Pugh, Mary Jo; Turner, Barbara J.] Univ Texas Hlth Sci Ctr San Antonio, Res Adv Community Hlth Ctr ReACH Ctr, San Antonio, TX 78229 USA. [Simmonds, Maureen J.; Finley, Erin P.; Pugh, Mary Jo; Turner, Barbara J.] South Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Finley, Erin P.; Pugh, Mary Jo] Univ Texas Sch Publ Hlth, Houston, TX USA. RP Turner, BJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, ReACH Ctr, 7411 John Smith Rd,Suite 1050, San Antonio, TX 78229 USA. EM turner@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 FU Elizabeth Huth Coates Charitable Foundation of 1992 FX We gratefully acknowledge funding from the Elizabeth Huth Coates Charitable Foundation of 1992. We also would like to thank Gregorio E. Pedroza III, MD, for his invaluable help in conducting this study. NR 29 TC 7 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD APR PY 2015 VL 16 IS 4 BP 726 EP 732 DI 10.1111/pme.12626 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CF5SP UT WOS:000352617600015 PM 25528887 ER PT J AU van Rhee, F Rothman, M Ho, KF Fleming, S Wong, RS Fossa, A Dispenzieri, A Cavet, J Munshi, N Vermeulen, J Casper, C AF van Rhee, Frits Rothman, Margaret Ho, Kai Fai Fleming, Sarah Wong, Raymond S. Fossa, Alexander Dispenzieri, Angela Cavet, James Munshi, Nikhil Vermeulen, Jessica Casper, Corey TI Patient-reported Outcomes for Multicentric Castleman's Disease in a Randomized, Placebo-controlled Study of Siltuximab SO PATIENT-PATIENT CENTERED OUTCOMES RESEARCH LA English DT Article ID LYMPH-NODE HYPERPLASIA; ORPHAN DISEASE; ANTIBODY; THERAPY AB Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently shown to be effective in a registration clinical trial. MCD symptoms, such as fatigue, pain, and weakness, are most appropriately quantified using patient-reported outcome (PRO) measures. We assessed the effect of siltuximab on patient perception of symptoms, functional status, and wellbeing using PRO instruments. We analyzed results of a randomized, double-blind trial comparing siltuximab 11 mg/kg every 3 weeks with placebo to treat MCD. Subjects (N = 79) completed the recently developed MCD-Symptom Scale (MCD-SS), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, and the Short Form (SF)-36 at predetermined time points throughout the treatment period. Scores were compared at baseline and over time between the treatment arms and PRO instruments. At baseline, the mean number of symptoms reported was 9.2 (standard deviation 3.76) out of 16 total, as measured by the MCD-SS. Fatigue was a key symptom across all PRO instruments. Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD-SS and FACIT-Fatigue scale. Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health. Patients with MCD commonly report impairments in functioning, wellbeing, and fatigue at baseline. Siltuximab-treated patients reported significant improvements in these outcomes after treatment. C1 [van Rhee, Frits] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Rothman, Margaret] Janssen Res & Dev, Washington, GA USA. [Ho, Kai Fai] STAT TU Inc, Toronto, ON, Canada. [Fleming, Sarah] Janssen Res & Dev, Spring House, PA USA. [Wong, Raymond S.] Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Fossa, Alexander] Oslo Univ Hosp, Oslo, Norway. [Dispenzieri, Angela] Mayo Clin, Rochester, MN USA. [Cavet, James] Christie NHS Fdn Trust, Manchester, Lancs, England. [Cavet, James] Univ Manchester, Manchester, Lancs, England. [Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Vermeulen, Jessica] Janssen Res & Dev LLC, Leiden, Netherlands. [Casper, Corey] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP van Rhee, F (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. EM vanrheefrits@uams.edu OI Dispenzieri, Angela/0000-0001-8780-9512 FU Janssen Research and Development; Janssen; Celgene; Pfizer; Millennium; Janssen Research Development FX We thank the patients who participated in this study, and the investigators and their colleagues who cared for them. The MCD2001 study was funded by Janssen Research and Development. All authors were involved in all stages of manuscript preparation. All authors had access to the data and were responsible for its interpretation. Frits van Rhee, Raymond S. Wong, Alexander Fossa, Angela Dispenzieri, James Cavet, Nikhil Munshi, and Corey Casper were study investigators. Jessica Vermeulen acted as the responsible clinician for the study sponsor. Margaret Rothman, Kai Fai Ho, and Sarah Fleming were responsible for analyzing the PRO data. As corresponding author, Frits van Rhee acts as guarantor of the manuscript. The authors disclose the following support or interests: Frits van Rhee has served on advisory boards for Celgene, Janssen, Millennium, and Sanofi; Margaret Rothman was an employee and stockholder of Janssen Research and Development when the study was conducted; Kai Fai Ho is a paid consultant for Janssen Global Services, LLC, contracted to provide statistical support; Sarah Fleming holds stock and is an employee of Janssen Research and Development; Raymond S. Wong has received research funding and has served on advisory boards for Janssen; Alexander Fossa has received honoraria from Janssen; Angela Dispenzieri has received research funding from Celgene, Janssen, Pfizer, and Millennium; James Cavet has received research funding, and has served on advisory boards (unpaid) and speakers bureau for Janssen; Nikhil Munshi has received honoraria from Celgene, Onyx, Janssen, Sanofi-Aventis, and Oncopep; Jessica Vermeulen holds stock and is an employee of Janssen Research and Development; Corey Casper received consulting fees and research funding from Janssen to evaluate siltuximab. The decision to submit the manuscript was not influenced by the study sponsor and was made by all authors, the majority of whom were study investigators. Medical writing support was provided by Christopher Jones, PhD, of MedErgy, and was funded by Janssen Research & Development. NR 24 TC 5 Z9 5 U1 0 U2 4 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1178-1653 EI 1178-1661 J9 PATIENT JI Patient PD APR PY 2015 VL 8 IS 2 BP 207 EP 216 DI 10.1007/s40271-015-0120-5 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CF0IW UT WOS:000352227800010 PM 25736164 ER PT J AU Barger, JL Anderson, RM Newton, MA da Silva, C Vann, JA Pugh, TD Someya, S Prolla, TA Weindruch, R AF Barger, Jamie L. Anderson, Rozalyn M. Newton, Michael A. da Silva, Cristina Vann, James A. Pugh, Thomas D. Someya, Shinichi Prolla, Tomas A. Weindruch, Richard TI A Conserved Transcriptional Signature of Delayed Aging and Reduced Disease Vulnerability Is Partially Mediated by SIRT3 SO PLOS ONE LA English DT Article ID EXTENDS LIFE-SPAN; CALORIC RESTRICTION; GENE-EXPRESSION; INSULIN-RESISTANCE; DIETARY RESTRICTION; SKELETAL-MUSCLE; ADIPOSE-TISSUE; RHESUS-MONKEYS; MICE; METABOLISM AB Aging is the most significant risk factor for a range of diseases, including many cancers, neurodegeneration, cardiovascular disease, and diabetes. Caloric restriction (CR) without malnutrition delays aging in diverse species, and therefore offers unique insights into age-related disease vulnerability. Previous studies suggest that there are shared mechanisms of disease resistance associated with delayed aging, however quantitative support is lacking. We therefore sought to identify a common response to CR in diverse tissues and species and determine whether this signature would reflect health status independent of aging. We analyzed gene expression datasets from eight tissues of mice subjected to CR and identified a common transcriptional signature that includes functional categories of mitochondrial energy metabolism, inflammation and ribosomal structure. This signature is detected in flies, rats, and rhesus monkeys on CR, indicating aspects of CR that are evolutionarily conserved. Detection of the signature in mouse genetic models of slowed aging indicates that it is not unique to CR but rather a common aspect of extended longevity. Mice lacking the NAD-dependent deacetylase SIRT3 fail to induce mitochondrial and anti-inflammatory elements of the signature in response to CR, suggesting a potential mechanism involving SIRT3. The inverse of this transcriptional signature is detected with consumption of a high fat diet, obesity and metabolic disease, and is reversed in response to interventions that decrease disease risk. We propose that this evolutionarily conserved, tissue-independent, transcriptional signature of delayed aging and reduced disease vulnerability is a promising target for developing therapies for age-related diseases. C1 [Barger, Jamie L.; da Silva, Cristina; Prolla, Tomas A.; Weindruch, Richard] LifeGen Technol LLC, Madison, WI 53719 USA. [Anderson, Rozalyn M.; Pugh, Thomas D.; Weindruch, Richard] Univ Wisconsin, Dept Med, SMPH, Madison, WI USA. [Anderson, Rozalyn M.; Weindruch, Richard] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res, Educ & Clin Ctr, Madison, WI USA. [Newton, Michael A.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. [Newton, Michael A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Vann, James A.; Someya, Shinichi; Prolla, Tomas A.] Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. [Vann, James A.; Someya, Shinichi; Prolla, Tomas A.] Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. RP Barger, JL (reprint author), LifeGen Technol LLC, Madison, WI 53719 USA. EM Jamie.L.Barger@gmail.com FU National Institute on Aging [R01AG037000, P01AG011915, R01AG038679]; National Institute of General Medical Sciences [R21HG006568]; LifeGen Technologies, LLC FX Funding was provided by National Institute on Aging R01AG037000 (RMA), National Institute on Aging P01AG011915 (RW), National Institute of General Medical Sciences R21HG006568 (MAN), and National Institute on Aging R01AG038679 (TAP). LifeGen Technologies, LLC, provided support in the form of salaries for authors JLB and CdS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section. NR 58 TC 5 Z9 5 U1 3 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 1 PY 2015 VL 10 IS 4 AR UNSP e0120738 DI 10.1371/journal.pone.0120738 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9AM UT WOS:000352135600037 PM 25830335 ER PT J AU Blanco, I Kuchenbaecker, K Cuadras, D Wang, XS Barrowdale, D Garibay, GR Librado, P Sanchez-Gracia, A Rozas, J Bonifaci, N McGuffog, L Pankratz, VS Islam, A Mateo, F Berenguer, A Petit, A Catala, I Brunet, J Feliubadalo, L Tornero, E Benitez, J Osorio, A Cajal, TRY Nevanlinna, H Aittomaki, K Arun, BK Toland, AE Karlan, BY Walsh, C Lester, J Greene, MH Mai, PL Nussbaum, RL Andrulis, IL Domchek, SM Nathanson, KL Rebbeck, TR Barkardottir, RB Jakubowska, A Lubinski, J Durda, K Jaworska-Bieniek, K Claes, K Van Maerken, T Diez, O Hansen, TV Jonson, L Gerdes, AM Ejlertsen, B de la Hoya, M Caldees, T Dunning, AM Oliver, C Fineberg, E Cook, M Peock, S McCann, E Murray, A Jacobs, C Pichert, G Lalloo, F Chu, C Dorkins, H Paterson, J Ong, KR Teixeira, MR Teixeira Hogervorst, FBL van der Hout, AH Seynaeve, C van der Luijt, RB Ligtenberg, MJL Devilee, P Wijnen, JT Rookus, MA Meijers-Heijboer, HEJ Blok, MJ van den Ouweland, AMW Aalfs, CM Rodriguez, GC Phillips, KAA Piedmonte, M Nerenstone, SR Bae-Jump, VL O'Malley, DM Ratner, ES Schmutzler, RK Wappenschmidt, B Rhiem, K Engel, C Meindl, A Ditsch, N Arnold, N Plendl, HJ Niederacher, D Sutter, C Wang-Gohrke, S Steinemann, D Preisler-Adams, S Kast, K Varon-Mateeva, R Gehrig, A Bojesen, A Pedersen, IS Sunde, L Jensen, UB Thomassen, M Kruse, TA Foretova, L Peterlongo, P Bernard, L Peissel, B Scuvera, G Manoukian, S Radice, P Ottini, L Montagna, M Agata, S Maugard, C Simard, J Soucy, P Berger, A Fink-Retter, A Singer, CF Rappaport, C Geschwantler-Kaulich, D Tea, MK Pfeiler, G John, EM Miron, A Neuhausen, SL Terry, MB Chung, WK Daly, MB Goldgar, DE Janavicius, R Dorfling, CM van Rensburg, EJ Fostira, F Konstantopoulou, I Garber, J Godwin, AK Olah, E Narod, SA Rennert, G Paluch, SS Laitman, Y Friedman, E Liljegren, A Rantala, J Stenmark-Askmalm, M Loman, N Imyanitov, EN Hamann, U Spurdle, AB Healey, S Weitzel, JN Herzog, J Margileth, D Gorrini, C Esteller, M Gomez, A Sayols, S Vidal, E Heyn, H Stoppa-Lyonnet, Leone, M Barjhoux, L Fassy-Colcombet, M de Pauw, A Lasset, C Ferrer, SF Castera, L Berthet, P Cornelis, F Bignon, YJ Damiola, F Mazoyer, S Sinilnikova, OM Maxwell, CA Vijai, J Robson, M Kauff, N Corines, MJ Villano, D Cunningham, J Lee, A Lindor, N Lazaro, C Easton, DF Offit, K Chenevix-Trench, G Couch, FJ Antoniou, AC Pujana, MA AF Blanco, Ignacio Kuchenbaecker, Karoline Cuadras, Daniel Wang, Xianshu Barrowdale, Daniel Ruiz de Garibay, Gorka Librado, Pablo Sanchez-Gracia, Alejandro Rozas, Julio Bonifaci, Nuria McGuffog, Lesley Pankratz, Vernon S. Islam, Abul Mateo, Francesca Berenguer, Antoni Petit, Anna Catala, Isabel Brunet, Joan Feliubadalo, Lidia Tornero, Eva Benitez, Javier Osorio, Ana Cajal, Teresa Ramon Y. Nevanlinna, Heli Aittomaki, Kristiina Arun, Banu K. Toland, Amanda E. Karlan, Beth Y. Walsh, Christine Lester, Jenny Greene, Mark H. Mai, Phuong L. Nussbaum, Robert L. Andrulis, Irene L. Domchek, Susan M. Nathanson, Katherine L. Rebbeck, Timothy R. Barkardottir, Rosa B. Jakubowska, Anna Lubinski, Jan Durda, Katarzyna Jaworska-Bieniek, Katarzyna Claes, Kathleen Van Maerken, Tom Diez, Orland Hansen, Thomas V. Jonson, Lars Gerdes, Anne-Marie Ejlertsen, Bent de la Hoya, Miguel Caldes, Trinidad Dunning, Alison M. Oliver, Clare Fineberg, Elena Cook, Margaret Peock, Susan McCann, Emma Murray, Alex Jacobs, Chris Pichert, Gabriella Lalloo, Fiona Chu, Carol Dorkins, Huw Paterson, Joan Ong, Kai-Ren Teixeira, Manuel R. Teixeira Hogervorst, Frans B. L. van der Hout, Annemarie H. Seynaeve, Caroline van der Luijt, Rob B. Ligtenberg, Marjolijn J. L. Devilee, Peter Wijnen, Juul T. Rookus, Matti A. Meijers-Heijboer, Hanne E. J. Blok, Marinus J. van den Ouweland, Ans M. W. Aalfs, Cora M. Rodriguez, Gustavo C. Phillips, Kelly-Anne A. Piedmonte, Marion Nerenstone, Stacy R. Bae-Jump, Victoria L. O'Malley, David M. Ratner, Elena S. Schmutzler, Rita K. Wappenschmidt, Barbara Rhiem, Kerstin Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hansjoerg J. Niederacher, Dieter Sutter, Christian Wang-Gohrke, Shan Steinemann, Doris Preisler-Adams, Sabine Kast, Karin Varon-Mateeva, Raymonda Gehrig, Andrea Bojesen, Anders Pedersen, Inge Sokilde Sunde, Lone Jensen, Uffe Birk Thomassen, Mads Kruse, Torben A. Foretova, Lenka Peterlongo, Paolo Bernard, Loris Peissel, Bernard Scuvera, Giulietta Manoukian, Siranoush Radice, Paolo Ottini, Laura Montagna, Marco Agata, Simona Maugard, Christine Simard, Jacques Soucy, Penny Berger, Andreas Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Geschwantler-Kaulich, Daphne Tea, Muy-Kheng Pfeiler, Georg John, Esther M. Miron, Alex Neuhausen, Susan L. Terry, Mary Beth Chung, Wendy K. Daly, Mary B. Goldgar, David E. Janavicius, Ramunas Dorfling, Cecilia M. van Rensburg, Elisabeth J. Fostira, Florentia Konstantopoulou, Irene Garber, Judy Godwin, Andrew K. Olah, Edith Narod, Steven A. Rennert, Gad Paluch, Shani Shimon Laitman, Yael Friedman, Eitan Liljegren, Annelie Rantala, Johanna Stenmark-Askmalm, Marie Loman, Niklas Imyanitov, Evgeny N. Hamann, Ute Spurdle, Amanda B. Healey, Sue Weitzel, Jeffrey N. Herzog, Josef Margileth, David Gorrini, Chiara Esteller, Manel Gomez, Antonio Sayols, Sergi Vidal, Enrique Heyn, Holger Stoppa-Lyonnet, Dominique Leone, Melanie Barjhoux, Laure Fassy-Colcombet, Marion de Pauw, Antoine Lasset, Christine Ferrer, Sandra Fert Castera, Laurent Berthet, Pascaline Cornelis, Francois Bignon, Yves-Jean Damiola, Francesca Mazoyer, Sylvie Sinilnikova, Olga M. Maxwell, Christopher A. Vijai, Joseph Robson, Mark Kauff, Noah Corines, Marina J. Villano, Danylko Cunningham, Julie Lee, Adam Lindor, Noralane Lazaro, Conxi Easton, Douglas F. Offit, Kenneth Chenevix-Trench, Georgia Couch, Fergus J. Antoniou, Antonis C. Angel Pujana, Miguel CA BCFR SWE-BRCA KConFab Investigators GEMO TI Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers SO PLOS ONE LA English DT Article ID GENETIC INTERACTION NETWORKS; GENOME-WIDE ASSOCIATION; EXPRESSION SIGNATURE; SUSCEPTIBILITY LOCI; CHIP-SEQ; CELL; POLYMORPHISM; MODIFIERS; SURVIVAL; ELEMENTS AB While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. C1 [Blanco, Ignacio; Feliubadalo, Lidia; Tornero, Eva; Lazaro, Conxi] Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Program, Catalan Inst Oncol ICO, Lhospitalet Del Llobrega, Catalonia, Spain. [Kuchenbaecker, Karoline; Barrowdale, Daniel; McGuffog, Lesley; Dunning, Alison M.; Oliver, Clare; Fineberg, Elena; Cook, Margaret; Peock, Susan; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Epidemiol Study Familial Breast Canc,Ctr Canc Gen, Cambridge, England. [Cuadras, Daniel; Berenguer, Antoni] Bellvitge Inst Biomed Res IDIBELL, Stat Unit, Lhospitalet Del Llobrega, Catalonia, Spain. [Wang, Xianshu; Cunningham, Julie; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Ruiz de Garibay, Gorka; Bonifaci, Nuria; Mateo, Francesca; Angel Pujana, Miguel] Bellvitge Inst Biomed Res IDIBELL, Breast Canc & Syst Biol Unit, Catalan Inst Oncol ICO, Lhospitalet Del Llobrega, Catalonia, Spain. [Librado, Pablo; Sanchez-Gracia, Alejandro; Rozas, Julio] Univ Barcelona, Dept Genet & Biodivers Res Inst IRBio, Barcelona, Catalonia, Spain. [Pankratz, Vernon S.; Cunningham, Julie; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Islam, Abul] Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh. [Petit, Anna; Catala, Isabel] Bellvitge Inst Biomed Res IDIBELL, Univ Hosp Bellvitge, Dept Pathol, Lhospitalet Del Llobrega, Catalonia, Spain. [Brunet, Joan] Hosp Josep Trueta, Girona Biomed Res Inst IDIBGI, Hereditary Canc Program, Catalan Inst Oncol ICO, Girona, Catalonia, Spain. [Benitez, Javier; Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. [Benitez, Javier; Osorio, Ana] Biomed Network Rare Dis, Madrid, Spain. [Cajal, Teresa Ramon Y.] Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Catalonia, Spain. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med & Mol Virol Immunol & Med Genet, Div Human Canc Genet, Columbus, OH 43210 USA. [Karlan, Beth Y.; Walsh, Christine; Lester, Jenny] Cedars Sinai Med Ctr, Ctr Comprehens Canc, Womens Canc Program Samuel Oschin, Los Angeles, CA 90048 USA. [Greene, Mark H.; Mai, Phuong L.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA. [Andrulis, Irene L.] Univ Toronto, Samuel Lunenfeld Res Inst, Mt Sinai Hosp, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. 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[Friedman, Eitan] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel. [SWE-BRCA] Swedish BRCA1 & BRCA2 Study SWE BRCA, Stockholm, Sweden. [Liljegren, Annelie] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Stenmark-Askmalm, Marie] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, Linkoping, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg, Russia. [Hamann, Ute] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany. [KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia. [Spurdle, Amanda B.; Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Weitzel, Jeffrey N.; Herzog, Josef] City Hope Natl Med Ctr, Clin Canc Genet, Duarte, CA USA. 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[Maxwell, Christopher A.] Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada. [Vijai, Joseph; Robson, Mark; Kauff, Noah; Corines, Marina J.; Villano, Danylko; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, New York, NY 10021 USA. [Lee, Adam] Mayo Clin, Dept Oncol, Rochester, MN USA. [Lindor, Noralane] Mayo Clin Scottsdale, Ctr Individualized Med, Scottsdale, AZ USA. RP Antoniou, AC (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Epidemiol Study Familial Breast Canc,Ctr Canc Gen, Cambridge, England. EM aca20@medschl.cam.ac.uk; mapujana@iconcologia.net RI Spurdle, Amanda/A-4978-2011; Feliubadalo, Lidia/G-4577-2016; Rozas, Julio/A-1733-2009; Sanchez-Gracia, Alejandro/F-4686-2014; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Ehrencrona, Hans/M-5619-2014; Gomez Moruno, Antonio/H-7574-2015; montagna, marco/E-2225-2012; Vidal, Enrique/A-9455-2014; Maxwell, Christopher/B-3044-2011; Esteller, Manel/L-5956-2014; Ligtenberg, Marjolijn/N-9666-2013; Vidal, Enrique/J-7118-2015; Osorio, Ana/I-4324-2014; Teixeira, Manuel/E-4885-2011; Andrulis, Irene/E-7267-2013; OMalley, David/E-3789-2011; Mateo, Francesca/K-7746-2015; Saunders, Christobel/H-5779-2014; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; OI Blanco, Ignacio/0000-0002-7414-7481; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; Phillips, Kelly-Anne/0000-0002-0475-1771; Feliubadalo, Lidia/0000-0002-1736-0112; Sunde, Lone/0000-0002-8479-165X; Dunning, Alison Margaret/0000-0001-6651-7166; Brunet, Joan/0000-0003-1945-3512; Kauff, Noah/0000-0001-7242-6156; Sayols, Sergi/0000-0002-3877-4170; Joseph, Vijai/0000-0002-7933-151X; Heyn, Holger/0000-0002-3276-1889; Rozas, Julio/0000-0002-6839-9148; Sanchez-Gracia, Alejandro/0000-0003-4543-4577; Ehrencrona, Hans/0000-0002-5589-3622; Gomez Moruno, Antonio/0000-0001-5308-981X; montagna, marco/0000-0002-4929-2150; Vidal, Enrique/0000-0002-4217-1807; Maxwell, Christopher/0000-0002-0860-4031; Esteller, Manel/0000-0003-4490-6093; Ligtenberg, Marjolijn/0000-0003-1290-1474; Vidal, Enrique/0000-0002-4217-1807; Osorio, Ana/0000-0001-8124-3984; Teixeira, Manuel/0000-0002-4896-5982; Mateo, Francesca/0000-0002-2342-7010; Saunders, Christobel/0000-0003-2281-9829; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Robson, Mark/0000-0002-3109-1692; Berenguer-LLergo, Antoni/0000-0002-3742-8161; Cuadras, Daniel/0000-0001-8780-1764 FU National Cancer Institute [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja's municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network from the National Cancer Institute and the Office of the Director, National Institutes of Health; Hereditary Cancer Research Registry from the National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Fondazione IRCCS Istituto Nazionale Tumori; Cancer Research-United Kingdom grant [C12292/A11174, C1287/ A10118]; NHMRC Program Grant; DKFZ; European Union (European Social Fund-ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA; European Social Fund; Cancer Research United Kingdom Grants [C1287/A10118, C1287/A11990]; National Institute of Health Research (NIHR) grant; NIHR grant; Royal Marsden NHS Foundation Trust; Cancer Research United Kingdom Grant [C5047/A8385]; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; AKG [5U01CA113916, R01CA140323]; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlonsen!" Award; Canadian Institutes of Health Research; Fund for Scientific Research Flanders (FWO); National Cancer Institute grant [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOG's Cancer Prevention and Control Committee [CA 101165]; Intramural Research Program, NCI; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grant [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hungarian Research Grant [KTIA-OTKA CK-80745]; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/OP-9]; Spanish Ministry of Health ISCIII FIS [PI10/01422, PI12/01528, PI13/00285]; RTICC [RD12/0036/0008]; Ramon Areces (XV) Foundation; Eugenio Rodriguez Pascual Foundation; Roses Contra el Cancer Foundation; Spanish Association Against Cancer (AECC); AGAUR Generalitat de Catalunya [2009-SGR290, 2009-SGR293]; Polish Foundation of Science; Icelandic Association "Walking for Breast Cancer Research"; Nordic Cancer Union; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade-grant [PSR-SIIRI-701]; Ministero dell'Istruzione, dell'Universita e della Ricerca and Ministero della Salute; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Foundation of Western Australia; Cancer Councils of Tasmania; National Institutes of Health grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; United States Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Jewish General Hospital Weekend; Quebec Ministry of Economic Development, Innovation and Export Trade; Cancer Councils of South Australia; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; MH CZ-DRO (MMCI) [00209805]; Niehaus Family Genetics Research Fund; STARR Cancer Consortium Grant; NAROD [1R01 CA149429-01]; NCI Intramural Research Program, National Institutes of Health [NO2-CP-11019-50, N02-CP-65504]; Westat, Inc, Rockville, Maryland; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant from the National Cancer Institute [UM1 CA164920]; Breast Cancer Family Registry (BCFR); United States Government or the BCFR; Ohio State University Comprehensive Cancer Center; Isreal cancer association; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; SAF2010-20493; [PBZ_KBN_122/P05/2004]; Associazione Italiana per la Ricerca sul Cancro FX BCFR-all. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government or the BCFR. BFBOCC: BFBOCC is supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012 and Hereditary Cancer Association (Paveldimo vezio asociacija); Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr. 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and Liepaja's municipal council. BMBSA: BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to EJR. BRICOH: SLN was partially supported by the Morris and Horowitz Familes Endowed Professorship. CBCS: This work was supported by the NEYE Foundation. CNIO: This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA) and SAF2010-20493. COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: JW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to SM. Italian Association for Cancer Research (AIRC) to LO. CORE: The CIMBA data management and data analysis were supported by Cancer Research-United Kingdom grants C12292/A11174 and C1287/A10118. SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer Research -United Kingdom Senior Cancer Research Fellow. GCT is an NHMRC Senior Principal Research Fellow. DKFZ: The DKFZ study was supported by the DKFZ. DEMOKRITOS: This research has been co-financed by the European Union (European Social Fund-ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. Investing in knowledge society through the European Social Fund. EMBRACE: EMBRACE is supported by Cancer Research United Kingdom Grants C1287/A10118 and C1287/A11990. DGE and FL are supported by an National Institute of Health Research (NIHR) grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. RE and EB are supported by Cancer Research United Kingdom Grant C5047/A8385. FCCC: The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship.; GC-HBOC: The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, RKS) and by the Center for Molecular Medicine Cologne (CMMC). GEMO: The study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlonsen!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. G-FAST: TVM is a postdoctoral researcher funded by the Fund for Scientific Research Flanders (FWO). GOG: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). MHG, PLM and Dr. Savage were supported by funding from the Intramural Research Program, NCI. HCSC: Was supported by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HUNBOCS: Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. ICO: The ICO-IDIBELL study was supported by grants from the Spanish Ministry of Health ISCIII FIS (PI10/01422, PI12/01528, and PI13/00285) and RTICC (RD12/0036/0008); the Ramon Areces (XV), Eugenio Rodriguez Pascual (2012), and Roses Contra el Cancer (2012) Foundations; the Spanish Association Against Cancer (AECC 2010); and the AGAUR Generalitat de Catalunya (2009-SGR290 and 2009-SGR293). IHCC: The IHCC was supported by Grant PBZ_KBN_122/P05/2004; Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. ILUH: The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research", by the Nordic Cancer Union and by the Landspitali University Hospital Research Fund. INHERIT: This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. IOVHBOCS: The study was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca and Ministero della Salute. IPOBCS: This study was in part supported by Liga Portuguesa Contra o Cancro. KCONFAB: kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. GCT and ABS are NHMRC Senior Research Fellows.; MAYO: MAYO is supported by National Institutes of Health grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a United States Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. MODSQUAD: The work was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) and MH CZ-DRO (MMCI, 00209805). MSKCC: MSKCC is supported by Breast Cancer Research Foundation, the Niehaus Family Genetics Research Fund, and the STARR Cancer Consortium Grants. NAROD: 1R01 CA149429-01. NCI: The research of MHG and PLM was supported by the NCI Intramural Research Program, National Institutes of Health, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, Maryland. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). NICCC: NICCC is supported by Clalit Health Services in Israel. Some of it's activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York. NNPIO: This work has been supported by the Russian Federation for Basic Research (grants 11-04-00227, 12-04-00928 and 12-04-01490) and the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780). OCGN: This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government or the BCFR. OSUCCG: OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. SMC: This project was partially funded through a grant by the Isreal cancer association and the funding for the Israeli Inherited breast cancer consortium. SWE-BRCA: SWE-BRCA collaborators are supported by the Swedish Cancer Society. UCHICAGO: UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. WCP: The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 2 Z9 2 U1 2 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 1 PY 2015 VL 10 IS 4 AR UNSP e0120020 DI 10.1371/journal.pone.0120020 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9AM UT WOS:000352135600019 PM 25830658 ER PT J AU Winnier, DA Fourcaudot, M Norton, L Abdul-Ghani, MA Hu, SL Farook, VS Coletta, DK Kumar, S Puppala, S Chittoor, G Dyer, TD Arya, R Carless, M Lehman, DM Curran, JE Cromack, DT Tripathy, D Blangero, J Duggirala, R Goring, HHH DeFronzo, RA Jenkinson, CP AF Winnier, Deidre A. Fourcaudot, Marcel Norton, Luke Abdul-Ghani, Muhammad A. Hu, Shirley L. Farook, Vidya S. Coletta, Dawn K. Kumar, Satish Puppala, Sobha Chittoor, Geetha Dyer, Thomas D. Arya, Rector Carless, Melanie Lehman, Donna M. Curran, Joanne E. Cromack, Douglas T. Tripathy, Devjit Blangero, John Duggirala, Ravindranath Goering, Harald H. H. DeFronzo, Ralph A. Jenkinson, Christopher P. TI Transcriptomic Identification of ADH1B as a Novel Candidate Gene for Obesity and Insulin Resistance in Human Adipose Tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES) SO PLOS ONE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; GENOME-WIDE ASSOCIATION; ETHANOL-PRODUCTION; GLUCOSE-TOLERANCE; LINKAGE ANALYSIS; NONALCOHOLIC STEATOHEPATITIS; ADIPOGENIC DIFFERENTIATION; ALCOHOL-DEHYDROGENASE; FAMILY-HISTORY AB Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR <= 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR <= 10(-4)) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10(-60)) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10(-9)), BMI (5.4 x 10(-6)), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits. C1 [Winnier, Deidre A.; Fourcaudot, Marcel; Norton, Luke; Abdul-Ghani, Muhammad A.; Tripathy, Devjit; DeFronzo, Ralph A.; Jenkinson, Christopher P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA. [Hu, Shirley L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Farook, Vidya S.; Kumar, Satish; Puppala, Sobha; Chittoor, Geetha; Dyer, Thomas D.; Carless, Melanie; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Goering, Harald H. H.; Jenkinson, Christopher P.] Texas Biomed Res Inst, San Antonio, TX USA. [Cromack, Douglas T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Orthoped, San Antonio, TX 78229 USA. [Arya, Rector] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, Div Endocrinol & Diabet, San Antonio, TX 78229 USA. [Lehman, Donna M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Cromack, Douglas T.; Tripathy, Devjit; DeFronzo, Ralph A.; Jenkinson, Christopher P.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Coletta, Dawn K.] Arizona State Univ, Sch Life Sci, Tempe, AZ USA. RP Jenkinson, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA. EM jenkinsonc@uthscsa.edu RI Coletta, Dawn/G-6382-2016; OI Coletta, Dawn/0000-0001-5819-5152; Norton, Luke/0000-0002-0231-5722 FU Veterans Administration: Merit Review Award [11487646]; Genetic Epidemiologic Grant; National Institutes of Health [DK79195, DK067690, DK53889, HD41111, DK70746, MH59490] FX This study was supported in part by grants from the Veterans Administration: Merit Review Award 11487646 (CPJ) and Genetic Epidemiologic Grant (RAD) and the National Institutes of Health: DK79195 (CPJ), DK067690 (CPJ), DK53889 (RD), HD41111 (RD), DK70746 (DML) and MH59490 (JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 3 Z9 3 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 1 PY 2015 VL 10 IS 4 AR e0119941 DI 10.1371/journal.pone.0119941 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9AM UT WOS:000352135600017 PM 25830378 ER PT J AU Palomaki, GE Haddow, JE Haddow, HRM Salahuddin, S Geahchan, C Cerdeira, AS Verlohren, S Perschel, FH Horowitz, G Thadhani, R Karumanchi, SA Rana, S AF Palomaki, Glenn E. Haddow, James E. Haddow, Hamish R. M. Salahuddin, Saira Geahchan, Carl Cerdeira, Ana Sofia Verlohren, Stefan Perschel, Frank H. Horowitz, Gary Thadhani, Ravi Karumanchi, S. Ananth Rana, Sarosh TI Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia SO PRENATAL DIAGNOSIS LA English DT Article ID MATERNAL PLASMA-CONCENTRATIONS; PLACENTAL GROWTH-FACTOR; DEVELOP PREECLAMPSIA; PREGNANCY; HYPERTENSION; COMPLICATIONS; ACCURACY; PREDICTION; BIOMARKERS; MANAGEMENT AB IntroductionPreeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. MethodsWomen evaluated for suspected PE at a tertiary hospital (2009-2012) had pregnancy outcomes categorized as referent' or severe', based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered unclassified'. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. ResultsThree hundred twenty-eight singleton pregnancies presented at 34.0weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5:1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2-58) and 15 (95% CI 5.8-40) fold, respectively. ConclusionsThis validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. (c) 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. C1 [Palomaki, Glenn E.; Haddow, James E.] Brown Univ, Women & Infants Hosp, Dept Pathol & Lab Med, Alpert Med Sch, Providence, RI USA. [Palomaki, Glenn E.; Haddow, James E.; Haddow, Hamish R. M.] Savjani Inst Hlth Res, Windham, ME USA. [Salahuddin, Saira; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Salahuddin, Saira; Horowitz, Gary; Thadhani, Ravi; Karumanchi, S. Ananth; Rana, Sarosh] Harvard Univ, Sch Med, Boston, MA USA. [Geahchan, Carl; Cerdeira, Ana Sofia] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA. [Cerdeira, Ana Sofia] Gulbenkian Programme Adv Med Educ, Oporto, Portugal. [Verlohren, Stefan] Charite, Campus Virchow Clin, Dept Obstet, D-13353 Berlin, Germany. [Perschel, Frank H.] Charite, Dept Lab Med Clin Chem & Pathobiochem, D-13353 Berlin, Germany. [Horowitz, Gary] Beth Israel Deaconess Med Ctr, Clin Chem Lab, Boston, MA 02215 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. [Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chicago, IL 60637 USA. RP Rana, S (reprint author), Beth Israel Deaconess Med Ctr, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. EM saroshrana@gmail.com OI Verlohren, Stefan/0000-0003-3507-8636 FU NIH KO8 award FX SR is supported by NIH KO8 award, and SAK is an investigator of the Howard Hughes Medical Institute. NR 40 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-3851 EI 1097-0223 J9 PRENATAL DIAG JI Prenat. Diagn. PD APR PY 2015 VL 35 IS 4 BP 386 EP 393 DI 10.1002/pd.4554 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA CF4BN UT WOS:000352493500013 PM 25641027 ER PT J AU Lengacher, CA Reich, RR Paterson, CL Jim, HS Ramesar, S Alinat, CB Budhrani, PH Farias, JR Shelton, MM Moscoso, MS Park, JY Kip, KE AF Lengacher, Cecile A. Reich, Richard R. Paterson, Carly L. Jim, Heather S. Ramesar, Sophia Alinat, Carissa B. Budhrani, Pinky H. Farias, Jerrica R. Shelton, Melissa M. Moscoso, Manolete S. Park, Jong Y. Kip, Kevin E. TI The effects of mindfulness-based stress reduction on objective and subjective sleep parameters in women with breast cancer: a randomized controlled trial SO PSYCHO-ONCOLOGY LA English DT Article DE objective and subjective sleep parameters; breast cancer; mindfulness-based stress reduction; MBSR(BC) ID QUALITY-OF-LIFE; COGNITIVE-BEHAVIOR THERAPY; INSOMNIA; SYMPTOMS; OUTPATIENTS; DISTURBANCE; PREVALENCE; DISORDERS; SURVIVORS; MOOD AB ObjectiveThe purpose of this study was to investigate the effects of mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)) on multiple measures of objective and subjective sleep parameters among breast cancer survivors (BCS). MethodsData were collected using a two-armed randomized controlled design among BCS enrolled in either a 6-week MBSR(BC) program or a usual care (UC) group with a 12-week follow-up. The present analysis is a subset of the larger parent trial ( Identifier: NCT01177124). Seventy-nine BCS participants (mean age 57years), stages 0-III, were randomly assigned to either the formal (in-class) 6-week MBSR(BC) program or UC. Subjective sleep parameters (SSP) (i.e., sleep diaries and the Pittsburgh Sleep Quality Index (PSQI)) and objective sleep parameters (OSP) (i.e., actigraphy) were measured at baseline, 6 weeks, and 12weeks after completing the MBSR(BC) or UC program. ResultsResults showed indications of a positive effect of MBSR(BC) on OSP at 12weeks on sleep efficiency (78.2% MBSR(BC) group versus 74.6% UC group, p=0.04), percent of sleep time (81.0% MBSR(BC) group versus 77.4% UC group, p=0.02), and less number waking bouts (93.5 in MBSR(BC) group versus 118.6 in the UC group, p<0.01). Small nonsignificant improvements were found in SSP in the MBSR(BC) group from baseline to 6weeks (PSQI total score, p=0.09). No significant relationship was observed between minutes of MBSR(BC) practice and SSP or OSP. ConclusionsThese data suggest that MBSR(BC) may be an efficacious treatment to improve objective and subjective sleep parameters in BCS. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Lengacher, Cecile A.; Paterson, Carly L.; Ramesar, Sophia; Alinat, Carissa B.; Farias, Jerrica R.; Shelton, Melissa M.; Moscoso, Manolete S.; Kip, Kevin E.] Univ S Florida, Coll Nursing, Tampa, FL 33612 USA. [Reich, Richard R.] Univ South Florida Sarasota Manatee, Coll Arts & Sci, Sarasota, FL USA. [Reich, Richard R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Biostat, Tampa, FL 33612 USA. [Jim, Heather S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Hlth Outcomes & Behav Program, Tampa, FL 33612 USA. [Budhrani, Pinky H.] Harvard Univ, Sch Med, Dana Farber Inst, Boston, MA USA. [Park, Jong Y.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Canc Epidemiol, Tampa, FL 33612 USA. RP Lengacher, CA (reprint author), Univ S Florida, Coll Nursing, 12901 Bruce B Downs Blvd,MDC Box 22, Tampa, FL 33612 USA. EM clengach@health.usf.edu FU National Cancer Institute [3R01CA131080-02S1] FX The project described was supported by award number 3R01CA131080-02S1 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. This study protocol was approved by the institutional review board at the University of South Florida to ensure the ethical treatment of participants. NR 50 TC 12 Z9 14 U1 8 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD APR PY 2015 VL 24 IS 4 BP 424 EP 432 DI 10.1002/pon.3603 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CF6FU UT WOS:000352653300008 PM 24943918 ER PT J AU Zhang, CY Blashill, AJ Wester, SR O'Neil, JM Vogel, DL Wei, J Zhang, JF AF Zhang, Chunyu Blashill, Aaron J. Wester, Stephen R. O'Neil, James M. Vogel, David L. Wei, Jia Zhang, Jinfu TI Factor Structure of the Gender Role Conflict Scale-Short Form in Chinese Heterosexual and Gay Samples SO PSYCHOLOGY OF MEN & MASCULINITY LA English DT Article DE gender role conflict; Chinese men; measurement invariance; gay men; heterosexual men ID COVARIANCE STRUCTURE-ANALYSIS; OF-FIT INDEXES; MEASUREMENT INVARIANCE; COUNSELING PSYCHOLOGY; MEDIATION; MODELS; MEN AB The current study examined the validity of Gender Role Conflict Scale-Short Form (GRCS-SF) among a sample of 256 Chinese heterosexual men and 250 Chinese gay men. Confirmatory factor analysis (CFA) supported the conclusion that a Chinese translated version of the GRCS-SF had acceptable structural validity. Specifically, the four-factor solution (i. e., Success, Power, Competition; Restricted Emotionality; Restricted Affectionate Behavior Between Men; Conflict Between Work and Family Relations) was confirmed with all items loading on their respective factors. Furthermore, the four-factor solution provided a better fit than either a single factor or a four-factor solution with a higher-order single factor. Cronbach's alpha reliabilities reached the acceptable criterion in both samples for the overall score as well as for the subscale scores. Measurement invariance also suggested that the GRCS-SF has a similar structure between heterosexual and gay Chinese men. C1 [Zhang, Chunyu; Wei, Jia; Zhang, Jinfu] Southwest Univ, Fac Psychol, Chongqing 400715, Peoples R China. [Blashill, Aaron J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Wester, Stephen R.] Univ Wisconsin Milwaukee, Educ Psychol, Milwaukee, WI USA. [O'Neil, James M.] Univ Connecticut, Dept Educ Psychol, Storrs, CT USA. [Vogel, David L.] Iowa State Univ, Dept Psychol, Ames, IA USA. RP Zhang, JF (reprint author), Southwest Univ, Fac Psychol, 2 Tiansheng Rd, Chongqing 400715, Peoples R China. EM zhangjf@swu.edu.cn FU NIMH NIH HHS [K23 MH096647] NR 33 TC 1 Z9 1 U1 2 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1524-9220 EI 1939-151X J9 PSYCHOL MEN MASCULIN JI Psychol. Men Masculinity PD APR PY 2015 VL 16 IS 2 BP 229 EP 233 DI 10.1037/a0036154 PG 5 WC Psychology, Social SC Psychology GA CF7LX UT WOS:000352739100013 PM 26185486 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Do Hospital-Acquired Condition Scores Correlate With Patients' Perspectives of Care? SO QUALITY MANAGEMENT IN HEALTH CARE LA English DT Article DE HAC; HCAHPS; quality; satisfaction ID QUALITY-OF-CARE; HEALTH-CARE; PATIENTS PERCEPTION; MEDICAL ERRORS; US HOSPITALS; SATISFACTION; OUTCOMES; SAFETY; PERFORMANCE; NONPAYMENT AB Beginning in fiscal year 2015, the federal Hospital-Acquired Condition (HAC) Reduction Program requires the Centers for Medicare & Medicaid Services to reduce payments by 1% for hospitals in the top quartile of risk-adjusted national HAC scores. The HAC penalty underscores the need for hospitals to become increasingly quality-and safety-focused, which could negatively affect their performance on patient satisfaction with care, another key performance metric tied to reimbursement. Using publicly available data through the Centers for Medicare & Medicaid Services Hospital Compare program, we assessed the correlation between preliminary HAC scores and patients' perspectives of care, as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems survey. Higher quality of care (lower HAC score) was modestly associated with a better patient experience (r = -0.090, P < .001). Additional research is needed to ensure that national policy efforts are not working at cross purposes and there need not be a trade-off between delivering high quality of care and patient satisfaction. C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM memenendez@partners.org NR 34 TC 0 Z9 0 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1063-8628 EI 1550-5154 J9 QUAL MANAG HEALTH CA JI Qual. Manag. Health Care PD APR-JUN PY 2015 VL 24 IS 2 BP 69 EP 73 DI 10.1097/QMH.0000000000000056 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CE9WC UT WOS:000352193100003 PM 25830614 ER PT J AU Slatore, CG Au, DH Press, N Wiener, RS Golden, SE Ganzini, L AF Slatore, Christopher G. Au, David H. Press, Nancy Wiener, Renda Soylemez Golden, Sara E. Ganzini, Linda TI Decision making among Veterans with incidental pulmonary nodules: A qualitative analysis SO RESPIRATORY MEDICINE LA English DT Article DE Pulmonary nodule; Lung cancer; Shared decision making ID LUNG-CANCER; HEALTH-CARE; RADIATION-EXPOSURE; FLEISCHNER-SOCIETY; CLINICAL-PRACTICE; GUIDELINES; STATEMENT; MANAGEMENT; MODEL; SCANS AB Purpose: Among patients undergoing lung cancer evaluation for newly diagnosed, incidental pulmonary nodules, it is important to evaluate the shared power and responsibility domain of patient-centered communication. We explored Veterans' perceptions of decision making with regards to an incidentally-detected pulmonary nodule. Methods: We conducted semi-structured, qualitative interviews of 19 Veterans from one medical center with incidentally-detected pulmonary nodules that were judged as having a low risk for malignancy. We used qualitative description for the analysis, focusing on patients' perceptions of shared decision making with their primary care provider (PCP). Interviews were conducted in 2011 and 2012. Results: Patients almost always played a passive role in deciding how and when to evaluate their pulmonary nodule for the possibility of malignancy. Some patients felt comfortable with this role, expressing trust that their clinician would provide the appropriate care. Other patients were not satisfied with how these decisions were made with some expressing concern that no decisions had actually occurred. Regardless of how satisfied they were with the decision, patients did not report discussing how they liked to make decisions with their PCP. Conclusions: Veterans in our study did not engage in shared decision making with their clinician. Some were satisfied with this approach although many would have preferred a shared approach. In order to reduce patient distress and improve satisfaction, clinicians may want to consider adopting a shared approach when making decisions about pulmonary nodule evaluation. Published by Elsevier Ltd. C1 [Slatore, Christopher G.; Golden, Sara E.; Ganzini, Linda] Portland VA Med Ctr, Hlth Serv Res Dev, Portland, OR USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David H.] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Press, Nancy] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. RP Slatore, CG (reprint author), 3710 SW US Vet Hosp Rd R&D 66, Portland, OR 97239 USA. EM christopher.slatore@va.gov OI Wiener, Renda/0000-0001-7712-2135; Slatore, Christopher/0000-0003-0958-8122 FU VA HSRD [CDP 11-227] FX This study was sponsored by a VA HSRD Career Development Award (CDP 11-227) to Dr. Slatore. It was also supported by resources from the Portland VA Medical Center, Portland, Oregon, the Puget Sound VA Healthcare System, Seattle, WA and the Edith Nourse Rogers Memorial VA Hospital, Bedford, Massachusetts. The Department of Veterans Affairs did not have a role in the conduct of the study, in the collection, management, analysis, interpretation of data, or in the preparation of the manuscript. NR 47 TC 2 Z9 2 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 EI 1532-3064 J9 RESP MED JI Respir. Med. PD APR PY 2015 VL 109 IS 4 BP 532 EP 539 DI 10.1016/j.rmed.2015.01.007 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA CE9PW UT WOS:000352176900013 PM 25660437 ER PT J AU Cheng, A Palaganas, J Eppich, W Rudolph, J Robinson, T Grant, V AF Cheng, Adam Palaganas, Janice Eppich, Walter Rudolph, Jenny Robinson, Traci Grant, Vincent TI Co-debriefing for Simulation-based Education A Primer for Facilitators SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Simulation; Facilitation; Debriefing; Co-facilitation; Co-debriefing; Education ID TECHNOLOGY-ENHANCED SIMULATION; RANDOMIZED-TRIAL; INCLUSION; METAANALYSIS; INSTRUCTION; TEACHERS; TOOL AB As part of simulation-based education, postevent debriefing provides an opportunity for learners to critically reflect on the simulated experience, with the goal of identifying areas in need of reinforcement and correcting areas in need of improvement. The art of debriefing is made more challenging when 2 or more educators must facilitate a debriefing together (ie, co-debriefing) in an organized and coordinated fashion that ultimately enhances learning. As the momentum for incorporating simulation-based health care education continues to grow, the need for faculty development in the area of co-debriefing has become essential. In this article, we provide a practical toolbox for co-facilitators by discussing the advantages of co-debriefing, describing some of the challenges associated with co-debriefing, and offering practical approaches and strategies to overcome themost common challenges associatedwith co-debriefing in the context of simulation-based health care education. C1 [Cheng, Adam; Robinson, Traci; Grant, Vincent] Univ Calgary, Alberta Childrens Hosp, KidSIM Simulat Program, Dept Pediat, Calgary, AB T3B 6A8, Canada. [Palaganas, Janice; Rudolph, Jenny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA. [Eppich, Walter] Ann & Robert H Lurie Childrens Hosp Chicago, Northwestern Feinberg Sch Med, Dept Med Educ, Chicago, IL 60611 USA. RP Cheng, A (reprint author), Univ Calgary, Alberta Childrens Hosp, KidSIM Simulat Program, Dept Pediat, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM chenger@me.com FU Center for Medical Simulation, Boston, MA FX W.E. teaches on multiple simulation educator courses. He receives salary support from the Center for Medical Simulation, Boston, MA. All salary support is paid to his institution to offset clinical duties. He receives intermittent per diem honoraria from PAEDSIM, a pediatric simulation collaborative in German-speaking countries, to teach simulation educator courses. NR 29 TC 3 Z9 3 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD APR PY 2015 VL 10 IS 2 BP 69 EP 75 DI 10.1097/SIH.0000000000000077 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CE9VZ UT WOS:000352192800002 PM 25710318 ER PT J AU Jalilvand, A Sarker, S Fisichella, PM AF Jalilvand, Anahita Sarker, Sharfi Fisichella, Piero M. TI A Rare Case of Mesh Infection 3 Years After a Laparoscopic Totally Extraperitoneal (TEP) Inguinal Hernia Repair SO SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES LA English DT Article DE totally extraperitoneal (TEP) repair; inguinal hernia repair; mesh infection ID FIXATION AB Late complications after a laparoscopic inguinal hernia repair are extremely rare and have only recently entered into the literature. One such late complication is mesh infection, of which there have been a handful of cases reported in the literature. Mesh infections occurring many years after inguinal hernia repairs are not only of significance because they are not well documented in the literature, and the pathogenesis and risk factors contributing to their development are not well understood. This report details a rare case of mesh infection 3 years after a laparoscopic totally extraperitoneal inguinal hernia repair, describes our management of the condition, highlights the current options for management, and attempts to define its pathophysiology. C1 [Jalilvand, Anahita; Sarker, Sharfi] Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. [Fisichella, Piero M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Boston VA Healthcare Syst, West Roxbury, MA 02132 USA. RP Fisichella, PM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Boston VA Healthcare Syst, 1400 VFW Pkwy 112, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1530-4515 EI 1534-4908 J9 SURG LAPARO ENDO PER JI Surg. Laparosc. Endosc. Pct. Tech. PD APR PY 2015 VL 25 IS 2 BP E69 EP E71 PG 3 WC Surgery SC Surgery GA CF0JV UT WOS:000352230800006 PM 25187073 ER PT J AU Dohlman, TH Omoto, M Hua, J Stevenson, W Lee, SM Chauhan, SK Dana, R AF Dohlman, Thomas H. Omoto, Masahiro Hua, Jing Stevenson, William Lee, Sang-Mok Chauhan, Sunil K. Dana, Reza TI VEGF-trap Aflibercept Significantly Improves Long-term Graft Survival in High-risk Corneal Transplantation SO TRANSPLANTATION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CHRONIC SKIN INFLAMMATION; MACULAR EDEMA SECONDARY; DRY EYE DISEASE; FACTOR-C; ALLOGRAFT-REJECTION; PENETRATING KERATOPLASTY; ADHESION MOLECULES; CELL-MIGRATION; T-CELLS AB Background. Graft failure because of immune rejection remains a significant problem in organ transplantation, and lymphatic and blood vessels are important components of the afferent and efferent arms of the host alloimmune response, respectively. We compare the effect of antihemangiogenic and antilymphangiogenic therapies on alloimmunity and graft survival in a murine model of high-risk corneal transplantation. Methods. Orthotopic corneal transplantation was performed in hemevascularized and lymph-vascularized high-risk host beds, and graft recipients received subconjunctival vascular endothelial growth factor (VEGF)-trap, anti-VEGF-C, sVEGFR-3, or no treatment, beginning at the time of surgery. Fourteen days after transplantation, graft hemeangiogenesis and lymphangiogenesis were evaluated by immunohistochemistry. The frequencies of Th1 cells in regional lymphoid tissue and graft-infiltrating immune cells were evaluated by flow cytometry. Long-term allograft survival was compared using Kaplan-Meier curves. Results. VEGF-trap significantly decreased graft hemangiogenesis as compared to the control group and was most effective in reducing the frequency of graft-infiltrating immune cells. Anti-VEGF-C and sVEGFR3 significantly decreased graft lymphangiogenesis and lymphoid Th1 cell frequencies as compared to control. VEGF-trap (72%), anti-VEGF-C (25%), and sVEGFR-3 (11%) all significantly improved in the 8-week graft survival compared to control (0%), although VEGF-trap was significantly more effective than both anti-VEGF-C (P < 0.05) and sVEGFR-3 (P < 0.05). Conclusion. In a clinically relevant model of high-risk corneal transplantation in which blood and lymphatic vessels are present and treatment begins at the time of transplantation, VEGF-trap is significantly more effective in improving long-term graft survival as compared to anti-VEGF-C and sVEGFR-3, but all approaches improve survival when compared to untreated control. C1 [Dohlman, Thomas H.; Omoto, Masahiro; Hua, Jing; Stevenson, William; Lee, Sang-Mok; Chauhan, Sunil K.; Dana, Reza] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Reza_Dana@meei.harvard.edu OI Lee, Sang-Mok/0000-0002-9018-8216 FU National Institutes of Health/National Eye Institute [EY012963]; Vegenics, Circadian Technologies Ltd. (Melbourne, Australia) FX This study was supported in part by the National Institutes of Health/National Eye Institute Grant EY012963 and Vegenics, Circadian Technologies Ltd. (Melbourne, Australia). NR 65 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD APR PY 2015 VL 99 IS 4 BP 678 EP 686 DI 10.1097/TP.0000000000000512 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA CE9HR UT WOS:000352155400016 PM 25606789 ER PT J AU Mera, T Faustman, DL AF Mera, Toshiyuki Faustman, Denise L. TI Removal of Donor Human Leukocyte Antigen Class I Proteins With Papain: Translation for Possible Whole Organ Practices SO TRANSPLANTATION LA English DT Article ID ISLET ALLOGRAFT SURVIVAL; CELLS; MASKING; MICE AB Background. Papain is a protease with potential use in transplantation because of its targeted capacity to selectively remove human leukocyte antigen (HLA) class I proteins from donor human cells. However, its proteolytic activity has not been studied under conditions suitable for use in perfusing donor organs, namely, under a temperature of 4 degrees C and dissolution in Belzer-UW solution. Methods. We test papain's HLA class I removing activity under recognized whole organ transplant conditions of lowered temperature. The activity of papain's substrate selectivity was tested using both a test substrate (casein) and fresh peripheral blood lymphocytes (PBLs). The activity of papain was also tested at 4 degrees C, the temperature of whole organ storage. Results. We found that papain at a range of concentrations is nearly as active in cleaving the test substrate in Belzer-UW solution as in distilled water. In distilled water, papain is as active in cleaving a test substrate at a temperature of 4 degrees C as compared to its optimal temperature of 37 degrees C, if the incubation time is extended from 10 min to 3 hr. This finding also holds true if papain is dissolved in Belzer UW solution. In peripheral blood lymphocytes, papain cleaved off HLA class I proteins as effectively at 4 degrees C as at 37 degrees C, provided the incubation time was also extended to 3 hr. Conclusion. These findings suggest that papain's targeted enzymatic cleavage of donor HLA class I has potential use in the whole organ transplant setting with retained activity at lower temperatures and when activated and dissolved in Belzer-UW solution. C1 [Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02129 USA. [Faustman, Denise L.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Bldg 149,13th St,Rm 3602, Boston, MA 02129 USA. EM faustman@helix.mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD APR PY 2015 VL 99 IS 4 BP 724 EP 730 DI 10.1097/TP.0000000000000436 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA CE9HR UT WOS:000352155400022 PM 25340603 ER PT J AU Verrier, RL Malik, M AF Verrier, Richard L. Malik, Marek TI Quantitative T-wave alternans analysis for guiding medical therapy: An underexploited opportunity SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR DYSFUNCTION; ACUTE CORONARY SYNDROME; HEART-RATE TURBULENCE; ACUTE MYOCARDIAL-INFARCTION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; SYMPATHETIC-NERVOUS-SYSTEM; PREDICT HIGH-RISK; ELECTRICAL INSTABILITY; HOLTER ELECTROCARDIOGRAMS AB Reducing the toll of sudden cardiac death (SCD) remains a major challenge in cardiology, as it is the leading cause of adult mortality in the industrially developed world, claiming 310,000 lives annually in the United States alone. The main contemporary noninvasive index of cardiovascular risk, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, is an attractive approach to risk stratification on both scientific and clinical grounds, as this ECG phenomenon has been shown using the FDA-cleared Spectral and Modified Moving Average methods to assess risk for cardiovascular mortality including SCD in studies enrolling >12,000 individuals with depressed or preserved LVEF. The evidence supporting TWA as a therapeutic target is reviewed. (c) 2015 Elsevier Inc. All rights reserved. C1 [Verrier, Richard L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. [Malik, Marek] Univ London, St Pauls Cardiac Electrophysiol, London, England. [Malik, Marek] Univ London Imperial Coll Sci Technol & Med, London, England. RP Verrier, RL (reprint author), Harvard Thorndike Electrophysiol Inst, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU Gilead Sciences, Inc. (Foster City, CA); Cyberonics, Inc. (Houston, TX) FX Dr. Verrier is co-inventor of the Modified Moving Average method for T-wave alternans analysis, with patent assigned to Georgetown University (Washington, DC) and Beth Israel Deaconess Medical Center (Boston, MA) and licensed to GE Healthcare, Inc. (Milwaukee, WI) and Medtronic, Inc. (Minneapolis, MN). He receives research grants from Gilead Sciences, Inc. (Foster City, CA) and Cyberonics, Inc. (Houston, TX). Dr. Malik declares no conflicts of interest. NR 89 TC 7 Z9 7 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD APR PY 2015 VL 25 IS 3 BP 201 EP 213 DI 10.1016/j.tcm.2014.10.006 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF1UX UT WOS:000352334500007 PM 25541329 ER PT J AU Isselbacher, EM AF Isselbacher, Eric M. TI MY APPROACH to stable thoracic aortic aneurysm SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Editorial Material C1 [Isselbacher, Eric M.] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Healthcare Transformat Lab, Boston, MA 02114 USA. [Isselbacher, Eric M.] Harvard Univ, Sch Med, Med, Boston, MA USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. EM EISSELBACHER@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD APR PY 2015 VL 25 IS 3 BP 263 EP 264 DI 10.1016/j.tcm.2014.08.012 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF1UX UT WOS:000352334500018 PM 25592240 ER PT J AU Chi, YW Raffetto, JD AF Chi, Yung-Wei Raffetto, Joseph D. TI Venous leg ulceration pathophysiology and evidence based treatment SO VASCULAR MEDICINE LA English DT Review DE chronic venous disorder; compression therapy; endovenous therapy; inflammation; venous disease classification; venous leg ulceration ID RANDOMIZED CONTROLLED-TRIAL; INTERMITTENT PNEUMATIC COMPRESSION; MATRIX-METALLOPROTEINASE ACTIVITY; PRIMARY VARICOSE-VEINS; GREAT SAPHENOUS-VEIN; CLINICAL-TRIAL; FREQUENCY ULTRASOUND; GENE POLYMORPHISMS; PERFORATING VEINS; CYTOKINE LEVELS AB Venous leg ulceration (VLU) is one of the most predominate medical disorders worldwide and in the western hemisphere it affects around 1.5% of the general population and up to 5% of the elderly population. Unfortunately, this trend will only increase given the growth of an aging population worldwide. Understanding its pathophysiology that begins with venous hemodynamic abnormalities and leads to inflammatory alterations with microcirculatory changes is critical to delivering effective curative therapy. As such, the main component to treatment is reversing the underlying venous hypertension and pro-inflammatory milieu using compression treatment along with various adjuvant therapies. Given its impact, a comprehensive multi-pronged approach to care, treatment and prevention is required to reverse the increasing trend that is observed worldwide. C1 [Chi, Yung-Wei] Univ Calif Davis, Med Ctr, Sect Cardiovasc Med, Dept Internal Med, Sacramento, CA 95817 USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, Div Vasc Surg, West Roxbury, MA USA. [Raffetto, Joseph D.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.] Harvard Univ, Sch Med, Boston, MA USA. RP Chi, YW (reprint author), Univ Calif Davis, Med Ctr, Sect Cardiovasc Med, Dept Internal Med, 4860 Y St Suite 3400, Sacramento, CA 95817 USA. EM ywchi@yahoo.com NR 97 TC 3 Z9 3 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD APR PY 2015 VL 20 IS 2 BP 168 EP 181 DI 10.1177/1358863X14568677 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF4VK UT WOS:000352550700012 PM 25832604 ER PT J AU Moy, AP Shahid, M Ferrone, CR Borger, DR Zhu, AX Ting, D Deshpande, V AF Moy, Andrea P. Shahid, Mohammad Ferrone, Cristina R. Borger, Darrell R. Zhu, Andrew X. Ting, David Deshpande, Vikram TI Microsatellite instability in gallbladder carcinoma SO VIRCHOWS ARCHIV LA English DT Article DE Gallbladder carcinoma; Microsatellite instability; Mismatch repair; LINE-1 ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH REPAIR; BILIARY-TRACT CANCERS; GROWTH-FACTOR-RECEPTOR; III COLON-CANCER; K-RAS; ENDOMETRIAL CARCINOMAS; LINE-1 HYPOMETHYLATION; MUTATIONAL ANALYSIS; SPORADIC CANCER AB The genetic abnormalities involved in the pathogenesis of gallbladder carcinoma (GBC) remain unclear. Microsatellite instability (MSI) has been described in many carcinomas, but little is known about the significance of mismatch repair in gallbladder carcinogenesis. Additionally, methylation status of long interspersed element-1 (LINE-1), a surrogate marker of global DNA methylation, has defined distinct subsets of other cancer types but has not been explored in GBC. Immunohistochemical expression of MSH2, MSH6, MLH1, and PMS2 and LINE-1 mRNA in situ hybridization was evaluated in 67 primary and 15 metastatic GBCs from 77 patients. Amplification of human epidermal growth factor receptor 2 (HER2) was evaluated by fluorescence in situ hybridization. Genotyping for 24 genes involved in carcinogenesis was performed using a multiplex PCR-based platform. MSI was present in 6 of 77 GBCs (7.8 %). Loss of MSH2/MSH6 was detected in five cases and loss of MLH1/PMS2 in one case. MSI status was not associated with Lynch syndrome, tumor grade, extracellular mucin, or tumor-infiltrating lymphocytes. There was no significant difference in mean overall survival of patients with and without MSI. Strong LINE-1 staining was identified in none of the GBC with MSI and in 36 of 69 (52 %) of those without MSI (p = 0.005), suggesting that LINE-1 in the former cohort was hypermethylated. All MSI tumors were negative for HER2 amplification, and TP53 and NRAS mutations were only found in GBC without MSI. MSI was identified in a minority of GBC cases. The strong correlation between global DNA methylation as measured by LINE-1 and loss of mismatch repair proteins suggests that methylation may account for the loss of these proteins. These hypermethylated tumors appear to represent a genetically unique cohort of gallbladder neoplasms, and the data suggests that demethylating agents may have a therapeutic value in this class of tumors. C1 [Moy, Andrea P.; Deshpande, Vikram] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Moy, Andrea P.; Shahid, Mohammad; Ferrone, Cristina R.; Borger, Darrell R.; Zhu, Andrew X.; Ting, David; Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shahid, Mohammad; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Borger, Darrell R.; Zhu, Andrew X.; Ting, David] Massachusetts Gen Hosp, Dept Med, Div Oncol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 256, Boston, MA 02114 USA. EM vdeshpande@partners.org OI Ting, David/0000-0002-3261-2322 FU Burroughs Wellcome Trust [K12CA087723-11A1]; Affymetrix, Inc. FX This work was supported by the Burroughs Wellcome Trust (DTT), K12CA087723-11A1 (DTT), and Affymetrix, Inc. (DTT, VD). NR 67 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD APR PY 2015 VL 466 IS 4 BP 393 EP 402 DI 10.1007/s00428-015-1720-0 PG 10 WC Pathology SC Pathology GA CF7BD UT WOS:000352710200005 PM 25680569 ER PT J AU Dhyani, M Anvari, A Samir, AE AF Dhyani, Manish Anvari, Arash Samir, Anthony E. TI Ultrasound elastography: liver SO ABDOMINAL IMAGING LA English DT Review DE Liver fibrosis; Elastography; Hepatitis C; Hepatitis B; Non-alcoholic fatty liver disease; Focal liver lesions; Portal hypertension ID CHRONIC HEPATITIS-C; RADIATION FORCE IMPULSE; UNIDIMENSIONAL TRANSIENT ELASTOGRAPHY; PRIMARY SCLEROSING CHOLANGITIS; SIMPLE NONINVASIVE INDEX; SHEAR-WAVE ELASTOGRAPHY; CHRONIC VIRAL-HEPATITIS; STIFFNESS MEASUREMENT; VIRUS-INFECTION; NONALCOHOLIC STEATOHEPATITIS AB Ultrasound elastography, also termed sonoelastography, is being used increasingly in clinical practice to aid the diagnosis and management of diffuse liver disease. Elastography has been shown to be capable of differentiating advanced and early-stage liver fibrosis, and consequently a major application in clinical liver care includes progression to cirrhosis risk stratification through (1) assessment of liver fibrosis stage in HCV and HBV patients, (2) distinguishing non-alcoholic steatohepatitis from simple steatosis in non-alcoholic fatty liver disease patients, and (3) prognostic evaluation of liver disease is autoimmune liver disease. In addition, elastographic characterization of focal liver lesions and evaluation of clinically significant portal hypertension have the potential to be clinically useful and are areas of active clinical research. C1 [Dhyani, Manish; Anvari, Arash; Samir, Anthony E.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dhyani, M (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dhyani.manish@mgh.harvard.edu RI Anvari, Arash/B-4329-2014; OI Anvari, Arash/0000-0001-5887-581X; Dhyani, Manish/0000-0002-2651-1859 NR 120 TC 3 Z9 3 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD APR PY 2015 VL 40 IS 4 BP 698 EP 708 DI 10.1007/s00261-015-0373-4 PG 11 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CE3AS UT WOS:000351697000003 PM 25690689 ER PT J AU Anvari, A Barr, RG Dhyani, M Samir, AE AF Anvari, Arash Barr, Richard G. Dhyani, Manish Samir, Anthony E. TI Clinical application of sonoelastography in thyroid, prostate, kidney, pancreas, and deep venous thrombosis SO ABDOMINAL IMAGING LA English DT Article DE Ultrasonography; Elasticity imaging technique; Strain elastography; Shear wave elastography; Thyroid nodules; Prostate cancer; Chronic kidney disease; Pancreas neoplasm; Deep vein thrombosis ID ACOUSTIC RADIATION FORCE; REAL-TIME ELASTOGRAPHY; SHEAR-WAVE ELASTOGRAPHY; TISSUE ELASTICITY QUANTIFICATION; ULTRASOUND ELASTOGRAPHY; IN-VIVO; DIFFERENTIAL-DIAGNOSIS; PREDICTING MALIGNANCY; IMPULSE ARFI; CANCER-DETECTION AB This article reviews the clinical applications of current ultrasound elastography methods in non-hepatic conditions including thyroid nodules, prostate cancer, chronic kidney disease, solid renal lesions, pancreatic lesions, and deep vein thrombosis. Pathophysiology alters tissue mechanical properties via ultrastructural changes including fibrosis, increased cellularity, bleeding, and necrosis, creating a target biomarker, which can be imaged qualitatively or quantitatively with US elastography. US elastography methods can add information to conventional US methods and improve the diagnostic performance of conventional US in a range of disease processes. C1 [Anvari, Arash; Dhyani, Manish; Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Barr, Richard G.] Case Western Reserve Univ, Dept Radiol, Sch Med, Cleveland, OH 44106 USA. RP Samir, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM asamir@mgh.harvard.edu RI Anvari, Arash/B-4329-2014; OI Anvari, Arash/0000-0001-5887-581X; Dhyani, Manish/0000-0002-2651-1859 NR 88 TC 5 Z9 6 U1 5 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD APR PY 2015 VL 40 IS 4 BP 709 EP 722 DI 10.1007/s00261-015-0383-2 PG 14 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CE3AS UT WOS:000351697000004 PM 25750099 ER PT J AU Butler, KL AF Butler, Kathryn L. TI Patient-Centered Instruction: The Cornerstone of Surgical Education SO ACADEMIC MEDICINE LA English DT Letter ID SURGEONS; IMPACT C1 [Butler, Kathryn L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Butler, Kathryn L.] Harvard Univ, Sch Med, Surg Clerkship, Boston, MA USA. RP Butler, KL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM klbutler@partners.org NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD APR PY 2015 VL 90 IS 4 BP 398 EP 398 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CE4BH UT WOS:000351775100002 PM 25803412 ER PT J AU Ripp, JA Bellini, L Fallar, R Bazari, H Katz, JT Korenstein, D AF Ripp, Jonathan A. Bellini, Lisa Fallar, Robert Bazari, Hasan Katz, Joel T. Korenstein, Deborah TI The Impact of Duty Hours Restrictions on Job Burnout in Internal Medicine Residents: A Three-Institution Comparison Study SO ACADEMIC MEDICINE LA English DT Article ID QUALITY-OF-LIFE; PATIENT-CARE; ASSOCIATION; FATIGUE; ERRORS; DISTRESS; SLEEPINESS; KNOWLEDGE; EDUCATION; PROGRAM AB Purpose Internal medicine (IM) residents commonly develop job burnout, which may lead to poor academic performance, depression, and medical errors. The extent to which duty hours restrictions (DHRs) can mitigate job burnout remains uncertain. The July 2011 DHRs created an opportunity to measure the impact of decreased work hours on developing burnout in IM residents. Method A survey was administered twice to first-year IM residents at three academic medical centers between June 2011 and July 2012. To estimate the impact of the 2011 DHRs, data from this cohort, including demographics, sleepiness, hospital-based patient service characteristics, and burnout measures, were compared with data from 2008-2009 from first-year IM residents at the same institutions. Results Of eligible residents, 128/188 (68%) from the 2011-2012 cohort and 111/180 (62%) from the 2008-2009 cohort completed both surveys. Year-end burnout prevalence (92/123 [75%] versus 91/108 [84%], P=.08) and incidence (59/87 [68%] versus 55/68 [81%], P=.07) did not differ significantly between cohorts. There was no difference in year-end prevalence of excessive Epworth sleepiness (72/122 [59%] versus 71/108 [66%], P=.29) between cohorts; however, a greater percentage of residents who developed burnout in the 2011-2012 cohort reported caring for >8 patients on their service (2011-2012 versus 2008-2009) (29/59 [49%] versus 5/34 [15%], P<.01). Conclusions Job burnout and self-reported sleepiness in IM resident physicians were unchanged after the 2011 DHRs at three academic institutions. Further investigation into the determinants of burnout can inform effective interventions. C1 [Ripp, Jonathan A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bellini, Lisa] Univ Penn, Perelman Sch Med, Internal Med Residency Training Program, Philadelphia, PA 19104 USA. [Fallar, Robert] Icahn Sch Med Mt Sinai, Dept Med Educ, New York, NY 10029 USA. [Bazari, Hasan] Massachusetts Gen Hosp, Internal Med Residency Training Program, Boston, MA 02114 USA. [Katz, Joel T.] Brigham & Womens Hosp, Internal Med Residency Training Program, Boston, MA 02115 USA. [Korenstein, Deborah] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Ripp, JA (reprint author), 1 Gustave L Levy Pl,Box 1216, New York, NY 10025 USA. EM Jonathan.Ripp@mountsinai.org OI Korenstein, Deborah/0000-0003-1859-0574; Fallar, Robert/0000-0002-2968-7630 FU Department of Medicine at the Mount Sinai Hospital FX No external support. The Department of Medicine at the Mount Sinai Hospital provided some financial support to cover the costs of survey administration and collection. NR 27 TC 10 Z9 10 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD APR PY 2015 VL 90 IS 4 BP 494 EP 499 DI 10.1097/ACM.0000000000000641 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CE4BH UT WOS:000351775100026 PM 25607940 ER PT J AU Grant, CC Kaur, S Waymouth, E Mitchell, EA Scragg, R Ekeroma, A Stewart, A Crane, J Trenholme, A Camargo, CA AF Grant, Cameron C. Kaur, Suhina Waymouth, Ellen Mitchell, Edwin A. Scragg, Robert Ekeroma, Alec Stewart, Alistair Crane, Julian Trenholme, Adrian Camargo, Carlos A., Jr. TI Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial SO ACTA PAEDIATRICA LA English DT Article DE Child; Clinical trial; Pregnancy; Respiratory tract infections; Vitamin D ID D DEFICIENCY; EARLY-CHILDHOOD; CHILDREN; PNEUMONIA; RISK; CONSEQUENCES; RICKETS; KABUL AB AimTo determine whether vitamin D supplementation reduces primary care visits for acute respiratory infection (ARI). MethodsA randomised, double-blind, placebo-controlled trial was conducted in New Zealand and powered to determine the vitamin D dose needed to achieve normal vitamin D status during infancy. Healthy pregnant women, from 27weeks' gestation to birth, and their infants, from birth to age 6months, were assigned to placebo or one of the two dosages of daily oral vitamin D-3. Woman/infant pairs were randomised to placebo/placebo, 1000IU/400IU or 2000IU/800IU. For this ad hoc analysis, the primary care records of enrolled children were audited to age 18months. ResultsTwo hundred and sixty pregnant women were randomised to placebo (n=87), lower-dose (n=87) or higher-dose (n=86) vitamin D-3. In comparison with the placebo group (99%), the proportion of children making any ARI visits was smaller in the higher-dose (87%, p=0.004), but not the lower-dose vitamin D-3 group (95%, p=0.17). The median number of ARI visits/child was less in the higher-dose vitamin D-3 group from age 6-18 months (placebo 4, lower dose 3, higher dose 2.5; p=0.048 for higher-dose vitamin D-3 vs. placebo). ConclusionVitamin D-3 supplementation during pregnancy and infancy reduces primary care visits for ARI during early childhood. C1 [Grant, Cameron C.; Waymouth, Ellen; Mitchell, Edwin A.] Univ Auckland, Dept Paediat Child & Youth Hlth, Auckland 1142, New Zealand. [Kaur, Suhina] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. [Scragg, Robert] Univ Auckland, Epidemiol & Biostat, Auckland 1, New Zealand. [Ekeroma, Alec] Univ Auckland, Obstet & Gynaecol, Auckland 1, New Zealand. [Crane, Julian] Univ Otago, Med, Wellington, New Zealand. [Trenholme, Adrian] Middlemore Hosp, Women & Childrens Hlth, Auckland 6, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med, Boston, MA USA. RP Grant, CC (reprint author), Univ Auckland, Fac Med & Hlth Sci, Dept Paediat Child & Youth Hlth, Private Bag 92019,Wellesley St, Auckland 1142, New Zealand. EM cc.grant@auckland.ac.nz OI Ekeroma, Alec/0000-0002-7581-8275; Scragg, Robert/0000-0003-0013-2620; Grant, Cameron/0000-0002-4032-7230 FU Health Research Council of New Zealand [09/215R]; University of Auckland Faculty Research Development Grant; Cure Kids FX The authors thank Tania Milne and Judy Rowden for their contributions to the design and administration of the study and for the recruitment and follow-up of study participants and the collection of study data. The authors thank Dr Clare Wall and Dr Sue Crengle for their contributions to the study design. The pregnancy and infancy vitamin D trial was funded by the Health Research Council of New Zealand, Grant Number 09/215R. A University of Auckland Faculty Research Development Grant provided the additional funding required for the primary care audit. Prof Mitchell is supported by Cure Kids. We thank the staff at all of the primary care practices for allowing us to complete an audit of the health records of the children enrolled in this study. NR 30 TC 12 Z9 13 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0803-5253 EI 1651-2227 J9 ACTA PAEDIATR JI Acta Paediatr. PD APR PY 2015 VL 104 IS 4 BP 396 EP 404 DI 10.1111/apa.12819 PG 9 WC Pediatrics SC Pediatrics GA CE3QV UT WOS:000351744200021 PM 25283480 ER PT J AU Jaff, MR Rosenfield, K Scheinert, D Rocha-Singh, K Benenati, J Nehler, M White, CJ AF Jaff, Michael R. Rosenfield, Kenneth Scheinert, Dierk Rocha-Singh, Krishna Benenati, James Nehler, Mark White, Christopher J. TI Drug-coated balloons to improve femoropopliteal artery patency: Rationale and design of the LEVANT 2 trial SO AMERICAN HEART JOURNAL LA English DT Article ID SUPERFICIAL FEMORAL-ARTERY; NITINOL STENT IMPLANTATION; PERFORMANCE-MEASURES; DISEASE; ANGIOPLASTY; PACLITAXEL; RESTENOSIS; LESIONS; ASSOCIATION; POPULATION AB Background Atherosclerotic peripheral artery disease (PAD) is common and results in limitations in quality of life and potential progression to limb loss. Options for therapy include medical therapy, supervised exercise, surgical revascularization, and, more recently, endovascular therapies to restore arterial perfusion to the limb. Endovascular revascularization has evolved over the past 2 decades, from percutaneous transluminal angioplasty (PTA) to self-expanding stents, atherectomy, laser angioplasty, and drug-eluting stents. Despite impressive technologic advances, PTA remains the standard of care at many institutions and is the recommended primary treatment modality for femoral-popliteal PAD according to current American College of Cardiology Foundation/American Heart Association guidelines. However, restenosis after PTA is common. Therefore, a significant clinical need remains for a device that is able to achieve more durable patency than PTA but does not require a permanent implant. Drug-coated balloons (DCBs) have the potential to address this need. Several randomized controlled clinical trials of PTA balloons coated with different formulations of paclitaxel have been conducted in Europe (N Engl J Med 2008; 358: 689-699) (Circulation 2008; 118: 1358-1365) (Circ Cardiovasc Interv 2012; 5: 831-840) (JACC Cardiovas Interv 2014; 7: 10-19) and demonstrated more durable efficacy than PTA with comparable safety. These studies were limited by small sample sizes and powered solely for an angiographic primary end point. The pivotal LEVANT 2 trial was designed in collaboration with the US Food and Drug Administration to demonstrate safety and efficacy in a large population and to obtain US Food and Drug Administration approval. Methods A prospective, multicenter, single-blind trial comparing the Lutonix DCB (Bard Lutonix; New Hope, MN) versus PTA for treatment of femoropopliteal PAD (LEVANT 2) is the first US-based 2: 1 randomized controlled trial of 476 patients with femoral-popliteal PAD designed to demonstrate superior efficacy and noninferior safety of a novel paclitaxel DCB compared with PTA. The primary efficacy end point is primary patency at 12 months. The primary safety end point is composite freedom at 12 months from perioperative death, index limb amputation, reintervention, and limb-related mortality. A series of important secondary end points include physical functioning, quality of life, revascularizations, and alternative measures of patency. To minimize bias potential for confounding variables, LEVANT 2 (1) excluded patients stented after predilation before randomization, (2) incorporated very stringent criteria for bailout stenting, (3) did not count bailout stenting as a target lesion revascularization or failure of any end point, (4) required a blinded clinician to perform clinical evaluations at follow-up, and (5) required clinical assessment before review of duplex ultrasound results. Conclusions LEVANT 2 represents the first US-inclusive multicenter, randomized controlled trial to assess the safety and efficacy of a novel DCB compared with PTA as primary therapy for symptomatic PAD on the background of standard medical therapy. C1 [Jaff, Michael R.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scheinert, Dierk] Univ Hosp Leipzig, Leipzig, Germany. [Rocha-Singh, Krishna] Prairie Heart Inst, Springfield, IL USA. [Benenati, James] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Nehler, Mark] Univ Colorado, Denver, CO 80202 USA. [White, Christopher J.] Univ Queensland, Ochsner Clin Sch, Ochsner Med Ctr, Dept Cardiovasc Dis, New Orleans, LA USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU Lutonix, Inc, CR Bard FX The LEVANT 2 trial is sponsored by Lutonix, Inc, a subsidiary of CR Bard. NR 24 TC 1 Z9 1 U1 3 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD APR PY 2015 VL 169 IS 4 BP 479 EP 485 DI 10.1016/j.ahj.2014.11.016 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE6MC UT WOS:000351949500010 PM 25819854 ER PT J AU Januzzi, JL Sharma, U Zakroysky, P Truong, QA Woodard, PK Pope, JH Hauser, T Mayrhofer, T Nagurney, JT Schoenfeld, D Peacock, WF Fleg, JL Wiviott, S Pang, PS Udelson, J Hoffmann, U AF Januzzi, James L. Sharma, Umesh Zakroysky, Pearl Truong, Quynh A. Woodard, Pamela K. Pope, J. Hector Hauser, Thomas Mayrhofer, Thomas Nagurney, J. Toby Schoenfeld, David Peacock, W. Frank Fleg, Jerome L. Wiviott, Stephen Pang, Peter S. Udelson, James Hoffmann, Udo TI Sensitive troponin assays in patients with suspected acute coronary syndrome: Results from the multicenter rule out myocardial infarction using computer assisted tomography II trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CHEST-PAIN; 3RD UNIVERSAL DEFINITION; EARLY-DIAGNOSIS; EMERGENCY-DEPARTMENT; TASK-FORCE; ANGIOGRAPHY AB Background Sensitive troponin (Tn) assays have been developed for the evaluation of patients with suspected acute coronary syndrome (ACS). We sought to compare the performance of a commercially available sensitive Tn I (sTnI) and precommercial highly sTnI (hsTnI) method to conventional Tn (cTn) assays. Methods Among patients with acute chest pain but normal cTn in the emergency department of 6 centers, sTnI and hsTnI were measured at baseline, 2 and 4 hours after presentation. Diagnostic accuracy of sTnI and hsTnI relative to cTn for diagnosis during index hospitalization as well as their associations with coronary artery disease in patients randomized to coronary computed tomographic angiography (CTA) was assessed. Results Overall, 322 patients were enrolled, of whom 161 had a CTA; 28 had ACS (8.7%), including 21 with unstable angina pectoris (UAP). Both sTnI and hsTnI values at baseline and second draw had significantly higher sensitivity for ACS and UAP than cTn and had significantly greater area under the receiver operator characteristic curve than cTn at first and second draws. Compared with cTn, 29% of ACS cases previously categorized as UAP were reclassified to acute myocardial infarction with sTnI or hsTnI. An hsTnI below limit of detection had 100% negative predictive value for ACS or significant coronary artery stenosis in those randomized to CTA. Conclusions In patients with acute chest discomfort, use of sTnI and hsTnI methods led to significant improvement in the early diagnostic accuracy for ACS, reclassifying one-third of UAP to myocardial infarction. Very low values for hsTnI excluded underlying coronary artery disease. C1 [Januzzi, James L.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sharma, Umesh; Mayrhofer, Thomas; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Zakroysky, Pearl; Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Woodard, Pamela K.] Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA. [Pope, J. Hector] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Hauser, Thomas] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Nagurney, J. Toby] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Boston, MA USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Wiviott, Stephen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Pang, Peter S.] Indiana Univ, Dept Emergency Med, Indianapolis, IN 46204 USA. [Udelson, James] Tufts Med Ctr, Dept Med, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU NHLBI NIH HHS [UO1HL092022, K23 HL098370, K23HL098370, K24 HL113128, L30 HL093806, L30HL093896, U01 HL092040, U01HL092040] NR 21 TC 3 Z9 3 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD APR PY 2015 VL 169 IS 4 BP 572 EP + DI 10.1016/j.ahj.2014.12.023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE6MC UT WOS:000351949500021 PM 25819865 ER PT J AU Willers, H Stinchcombe, TE Barriger, RB Chetty, IJ Ginsburg, ME Kestin, LL Kumar, S Loo, BW Movsas, B Rimner, A Rosenzweig, KE Videtic, GMM Chang, JYJ AF Willers, Henning Stinchcombe, Thomas E. Barriger, R. Bryan Chetty, Indrin J. Ginsburg, Mark E. Kestin, Larry L. Kumar, Sanath Loo, Billy W., Jr. Movsas, Benjamin Rimner, Andreas Rosenzweig, Kenneth E. Videtic, Gregory M. M. Chang, Joe Yujiao CA Expert Panel Radiation Oncology TI ACR Appropriateness Criteria (R) Induction and Adjuvant Therapy for N2 Non-small-cell Lung Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE non-small-cell lung carcinoma; stage III; induction therapy; adjuvant radiation therapy; appropriateness criteria ID POSTOPERATIVE RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; LEUKEMIA GROUP-B; VINORELBINE PLUS CISPLATIN; UNRESECTABLE STAGE-IIIA; INDIVIDUAL PATIENT DATA; HIGH-DOSE RADIATION; PHASE-II; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY AB The integration of chemotherapy, radiation therapy (RT), and surgery in the management of patients with stage IIIA (N2) non-small- cell lung carcinoma is challenging. The American College of Radiology (ACR) Appropriateness Criteria Lung Cancer Panel was charged to update management recommendations for this clinical scenario. The Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. There is limited level I evidence to guide patient selection for induction, postoperative RT (PORT), or definitive RT. Literature interpretation is complicated by inconsistent diagnostic procedures for N2 disease, disease heterogeneity, and pooled analysis with other stages. PORT is an appropriate therapy following adjuvant chemotherapy in patients with incidental pN2 disease. In patients with clinical N2 disease who are potential candidates for a lobectomy, both definitive and induction concurrent chemotherapy/RT are appropriate treatments. In N2 patients who require a pneumonectomy, definitive concurrent chemotherapy/RT is most appropriate although induction concurrent chemotherapy/RT may be considered in expert hands. Induction chemotherapy followed by surgery + / - PORT may also be an option in N2 patients. For pre-operative RT and PORT, 3-dimensional conformal techniques and intensity-modulated RT are most appropriate. C1 [Willers, Henning] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stinchcombe, Thomas E.] Univ North Carolina Hlth Care Syst, Amer Soc Clin Oncol, Chapel Hill, NC USA. [Barriger, R. Bryan] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Chetty, Indrin J.; Movsas, Benjamin] Henry Ford Hlth Syst, Detroit, MI USA. [Kumar, Sanath] Henry Ford Hosp, Detroit, MI 48202 USA. [Kestin, Larry L.] 21st Century Oncol Michigan Healthcare Profess, Farmington Hills, MI USA. [Ginsburg, Mark E.] Columbia Univ, Soc Thorac Surg, New York, NY USA. [Rimner, Andreas] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Rosenzweig, Kenneth E.] Mt Sinai Sch Med, New York, NY USA. [Loo, Billy W., Jr.] Stanford Univ, Stanford, CA 94305 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Videtic, Gregory M. M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Chang, Joe Yujiao] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM publications@acr.org FU Varian Inc.; Philips Inc.; Resonant Inc. FX R.B.B. D3 Oncology Solutions: co-chair of the Via Oncology Lung Cancer Pathways, co-chair of the Via Oncology Esophageal Pathways. B.M.-Research support to Henry Ford Health System Radiation Oncology Department from Varian Inc., Philips Inc., and Resonant Inc. H.W. received a stipend for work pertaining to the pathways committees. The other authors declare no conflicts of interest. NR 96 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2015 VL 38 IS 2 BP 197 EP 205 DI 10.1097/COC.0000000000000154 PG 9 WC Oncology SC Oncology GA CE3ZW UT WOS:000351770500013 PM 25803563 ER PT J AU Bradford, LS Rauh-Hain, JA Schorge, J Birrer, MJ Dizon, DS AF Bradford, Leslie S. Rauh-Hain, Jose Alejandro Schorge, John Birrer, Michael J. Dizon, Don S. TI Advances in the Management of Recurrent Endometrial Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE endometrial cancer; metastatic disease; chemotherapy; radiation therapy; surgery; chemoradiation; prognosis ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; PAPILLARY SEROUS CARCINOMA; GROWTH-FACTOR RECEPTOR; PELVIC EXENTERATION; CYTOREDUCTIVE SURGERY; LIPOSOMAL DOXORUBICIN; 2ND-LINE CHEMOTHERAPY; MAMMALIAN TARGET; RANDOMIZED-TRIAL AB Objective: Endometrial carcinoma is the most common malignancy of the female reproductive tract. Although most cases are diagnosed at an early stage, endometrial carcinoma carries a poor prognosis when it recurs after previous definitive treatment or when diagnosed at an advanced stage. The purpose of this review is to summarize the contemporary management of recurrent endometrial carcinoma. Methods: A literature review was conducted on the management of advanced, recurrent, or metastatic endometrial cancer to determine the best evidence to support the roles of surgery, radiation, and medical therapy. Results: Radiation therapy (RT) has a role in the treatment of a local or regional recurrence, especially in the patient who has not had prior RT. For selected patients who experience a loco-regional recurrence and who have been treated with RT, pelvic exenteration may be an option. Those patients with metastatic disease are not curable and should be considered for palliative chemotherapy. The data support the use of carboplatin and paclitaxel as an acceptable alternative to cisplatin-based regimens. For women who progress after first-line treatment, the options are limited. Current clinical trials are evaluating the role of angiogenesis inhibitors and molecularly targeted therapy (including the mammalian target of rapamycin inhibitors and multitargeted tyrosine kinase inhibitors) with the aim of identifying other novel agents that can be exploited for treatment of advanced disease. Conclusions: The treatment of women with advanced, recurrent, or metastatic endometrial cancer represents an unmet need in oncology. Robust clinical trials are required to explore how to improve on therapy. The incorporation of molecularly targeted agents has the potential to improve outcomes for women who require treatment in both the first-line and second-line settings. C1 [Bradford, Leslie S.; Rauh-Hain, Jose Alejandro; Schorge, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol,Canc Ctr,Gillette Ctr Gynecol, Boston, MA 02114 USA. [Birrer, Michael J.; Dizon, Don S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gillette Ctr Gynecol Oncol,Canc Ctr, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gillette Ctr Gynecol Oncol,Canc Ctr, Boston, MA 02114 USA. EM ddizon@partners.org NR 63 TC 10 Z9 12 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2015 VL 38 IS 2 BP 206 EP 212 DI 10.1097/COC.0b013e31829a2974 PG 7 WC Oncology SC Oncology GA CE3ZW UT WOS:000351770500014 PM 23764681 ER PT J AU Mateos, MV Richardson, PG Dimopoulos, MA Palumbo, A Anderson, KC Shi, HL Elliott, J Dow, E van de Velde, H Niculescu, L San Miguel, JF AF Victoria Mateos, Maria Richardson, Paul G. Dimopoulos, Meletios A. Palumbo, Antonio Anderson, Kenneth C. Shi, Hongliang Elliott, Jennifer Dow, Edward van de Velde, Helgi Niculescu, Liviu San Miguel, Jesus F. TI Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-melphalan-prednisone in the phase III VISTA SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID INITIAL TREATMENT; FOLLOW-UP; MAINTENANCE; TRIAL; THALIDOMIDE; THERAPY; DEXAMETHASONE; EFFICACY AB This analysis, using data from the bortezomib-melphalan-prednisone (VMP) arm of the Phase III VISTA study, investigated whether increased cumulative bortezomib dose could improve overall survival (OS) in transplant-ineligible patients with previously untreated multiple myeloma. Median cumulative bortezomib dose received by the 340 patients was 39 mg/m(2); this was selected as the cut-off for defining the dose groups to be compared for OS. Patient characteristics were well balanced between dose groups except for age. OS was significantly longer in the higher (39 mg/m(2)) versus lower (<39 mg/m(2)) cumulative bortezomib dose group (median 66.3 vs. 46.2 months; hazard ratio (HR) 0.533, P<0.0001; age-adjusted HR 0.561, P=0.0002). To overcome confounding effects of early discontinuations/deaths, which were more common in the lower cumulative dose group (27 vs. 4% of patients discontinued due to adverse events (AEs) in the lower and higher cumulative dose groups, respectively), a landmark analysis was conducted at 180 days, eliminating patients who died or discontinued before this time from the analysis. OS from this landmark remained significantly longer in the higher dose group (median 60.4 vs. 50.3 months; HR 0.709, P=0.0372). Thus, higher cumulative bortezomib dose, reflecting prolonged treatment duration and/or dose intensity, appears associated with improved OS. Approaches to achieve higher cumulative doses could include subcutaneous bortezomib administration, dose/schedule modifications, continuing therapy in responding patients, and proactive AE management. Am. J. Hematol. 90:314-319, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Victoria Mateos, Maria] Hosp Univ Salamanca, Inst Biosanitario Salamanca IBSAL, Salamanca 37007, Spain. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Alexandra Gen Hosp, Dept Clin Therapeut, GR-11527 Athens, Greece. [Palumbo, Antonio] Univ Turin, Azienda Osped Univ AOU S Giovanni Battista, Div Hematol, Myeloma Unit, Turin, Italy. [Shi, Hongliang] Millennium Pharmaceut Inc, Global Stat, Cambridge, MA USA. [Elliott, Jennifer; Dow, Edward; Niculescu, Liviu] Millennium Pharmaceut Inc, Global Med Affairs, Cambridge, MA USA. [van de Velde, Helgi] Janssen Res & Dev, Beerse, Belgium. [San Miguel, Jesus F.] Univ Navarra Clin, Ctr Invest Med Aplicada, Pamplona, Spain. RP Mateos, MV (reprint author), Hosp Univ Salamanca, Inst Biosanitario Salamanca IBSAL, Serv Hematol, Paseo San Vicente 58-182, Salamanca 37007, Spain. EM mvmateos@usal.es FU Celgene; Millennium: The Takeda Oncology Company FX M VM discloses consultancy for Millennium: The Takeda Oncology Company and Janssen. PGR discloses advisory board roles for Celgene, Janssen, and Millennium: The Takeda Oncology Company, and research funding from Celgene and Millennium: The Takeda Oncology Company. MAD discloses consultancy for, and honoraria from, Ortho-Biotech. AP discloses consultancy/advisory role and honoraria for Celgene and Janssen-Cilag. KCA discloses consultancy for Celgene, Onyx Pharmaceuticals, Gilead, Millennium: The Takeda Oncology Company and Sanofi-Aventis, and equity ownership in Acetylon and OncoPep. HS discloses employment with Takeda Pharmaceuticals International Co. JE, ED, and LN disclose employment with Millennium: The Takeda Oncology Company. HvdV discloses employment with Janssen Pharmaceutica NV and holds stock with Johnson & Johnson. JFSM discloses consultancy for Bristol-Myers Squibb, Celgene, Janssen, Millennium: The Takeda Oncology Company, Novartis and Onyx Pharmaceuticals. NR 24 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2015 VL 90 IS 4 BP 314 EP 319 DI 10.1002/ajh.23933 PG 6 WC Hematology SC Hematology GA CE2WE UT WOS:000351680800017 PM 25557740 ER PT J AU Forester, CM Sartain, SE Guo, DJ Harris, MH Weinberg, OK Fleming, MD London, WB Williams, DA Hofmann, I AF Forester, Craig M. Sartain, Sarah E. Guo, Dongjing Harris, Marian H. Weinberg, Olga K. Fleming, Mark D. London, Wendy B. Williams, David A. Hofmann, Inga TI Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis assessing outcomes and histomorphologic predictors SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY; MYELODYSPLASTIC SYNDROME; ANTITHYMOCYTE GLOBULIN; MARROW-TRANSPLANTATION; CYCLOSPORINE-A; WORKING PARTY; CHILDREN; CHILDHOOD; CLASSIFICATION; DIAGNOSIS AB Pediatric acquired aplastic anemia (AA) is a bone marrow disorder that is difficult to distinguish from inherited bone marrow failure syndromes and hypocellular refractory cytopenia of childhood (RCC). Historically, patients with hypocellular RCC have been given the diagnosis of AA. To assess the clinical and histologic distinction between RCC and AA, we performed a retrospective analysis of 149 patients previously diagnosed with AA between 1976 and 2010. We evaluated event free survival (EFS), overall survival (OS), response rates to immunosuppressive therapy, treatment-related toxicities and clonal evolution. The 5-year EFS and OS were 50.8%+/- 5.5% and 73.1%+/- 4.7%, respectively. Patients with very severe AA had worse OS compared to patients with severe and moderately severe AA. Seventy-two patients had diagnostic pathology specimens available for review. Three pediatric hematopathologists reviewed and reclassified these specimens as AA, RCC or Other based on 2008 WHO Criteria. The concordance between pathologists in the diagnosis of AA or RCC was modest. RCC was associated with a trend toward improved OS and EFS and was not prognostic of immunosuppression therapy treatment failure. There was a low rate of clonal evolution exclusively associated with moderately severe AA. Our findings indicate that a diagnosis of RCC is difficult to establish with certainty and does not predict outcomes, calling into question the reproducibility and clinical significance of the RCC classification and warranting further studies. Am. J. Hematol. 90:320-326, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Forester, Craig M.; Sartain, Sarah E.] Boston Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Guo, Dongjing; London, Wendy B.; Williams, David A.; Hofmann, Inga] Boston Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Harris, Marian H.; Weinberg, Olga K.; Fleming, Mark D.; Hofmann, Inga] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Hofmann, I (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Enders 1110, Boston, MA 02115 USA. EM inga.hofmann@childrens.harvard.edu FU National Cancer Institute [1K08CA140723]; National Institutes of Health Grants (National Institute of Diabetes and Digestive and Kidney Diseases) [1 R24 DK 094746-01] FX Contract grant sponsor: National Institutes of Health Grants (National Institute of Diabetes and Digestive and Kidney Diseases); Contract grant number: 1 R24 DK 094746-01.; Contract grant sponsor: National Cancer Institute; Contract grant number: 1K08CA140723. NR 25 TC 5 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2015 VL 90 IS 4 BP 320 EP 326 DI 10.1002/ajh.23937 PG 7 WC Hematology SC Hematology GA CE2WE UT WOS:000351680800018 PM 25580823 ER PT J AU Pena, JRA Saidman, SL AF Pena, Jeremy Ryan A. Saidman, Susan L. TI Anti-HLA antibody testing in hematology patients SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; PLATELET TRANSFUSION; GRAFT FAILURE; ALLOANTIBODIES; REFRACTORINESS; SPECIFICITY; SENSITIVITY; RECIPIENTS; DP AB Anti-human leukocyte antigens (HLA) antibodies can adversely impact the care of hematology patients. In particular, HLA antibody testing provides important information for optimal stem cell and platelet donor selection in the management of stem cell recipients and platelet refractory patients. Current testing methods for HLA antibodies are briefly reviewed, with particular emphasis on laboratory and clinical issues associated with solid-phase multiplex assays. Am. J. Hematol. 90:361-364, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Pena, Jeremy Ryan A.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Pena, Jeremy Ryan A.; Saidman, Susan L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Saidman, Susan L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Pena, JRA (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Div Lab & Transfus Med, YA 309,330 Brookline Ave, Boston, MA 02215 USA. EM jrpena@bidmc.harvard.edu FU NIH NHLBI [K12HL087164-07] FX Contract grant sponsor: NIH NHLBI; Contract grant number: K12HL087164-07. NR 25 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2015 VL 90 IS 4 BP 361 EP 364 DI 10.1002/ajh.23935 PG 4 WC Hematology SC Hematology GA CE2WE UT WOS:000351680800025 PM 25580568 ER PT J AU de Graaf, G Buckley, F Skotko, BG AF de Graaf, Gert Buckley, Frank Skotko, Brian G. TI Estimates of the Live Births, Natural Losses, and Elective Terminations with Down Syndrome in the United States SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE down syndrome; trisomy 21; prevalence; elective pregnancy termination ID SYNDROME PREGNANCIES; FETAL LOSS; PREVALENCE; DEFECTS; RATES; SURVEILLANCE; ANEUPLOIDY; ASCERTAINMENT; CERTIFICATE; DIAGNOSIS AB The present and future live birth prevalence of Down syndrome (DS) is of practical importance for planning services and prioritizing research to support people living with the condition. Live birth prevalence is influenced by changes in prenatal screening technologies and policies. To predict the future impact of these changes, a model for estimating the live births of people with DS is required. In this study, we combine diverse and robust datasets with validated estimation techniques to describe the non-selective and live birth prevalence of DS in the United States from 1900-2010. Additionally, for the period 1974-2010, we estimate the impact of DS-related elective pregnancy terminations (following a prenatal diagnosis of DS) on the live births with DS. The live birth prevalence for DS in the most recent years (2006-2010) was estimated at 12.6 per 10,000 (95% CI 12.4-12.8), with around 5,300 births annually. During this period, an estimated 3,100 DS-related elective pregnancy terminations were performed in the U.S. annually. As of 2007, the estimated rates at which live births with DS were reduced as a consequence of DS-related elective pregnancy terminations were 30% (95% CI: 27.3-31.9) for the U.S. as a whole. Our results and our model provide data on the impact of elective pregnancy terminations on live births with DS and may provide a baseline from which future trends for live births with DS can be estimated. (c) 2015 Wiley Periodicals, Inc. C1 [de Graaf, Gert] Dutch Syndrome Fdn, Meppel, Netherlands. [Buckley, Frank] Down Syndrome Educ Int, Kirkby Lonsdale, Cumbria, England. [Buckley, Frank] Down Syndrome Educ USA, Newport Beach, CA USA. [Skotko, Brian G.] Massachusetts Gen Hosp, Dept Pediat, Div Med Genet, Boston, MA 02114 USA. [Skotko, Brian G.] Harvard Univ, Sch Med, Boston, MA USA. RP Skotko, BG (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Room 2222, Boston, MA 02114 USA. EM bskotko@mgh.harvard.edu OI de Graaf, Gert/0000-0002-4990-5711 NR 45 TC 15 Z9 15 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2015 VL 167 IS 4 BP 756 EP 767 DI 10.1002/ajmg.a.37001 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CE7KQ UT WOS:000352019000014 PM 25822844 ER PT J AU Hall, MH Chen, CY Cohen, BM Spencer, KM Levy, DL Ongur, D Smoller, JW AF Hall, Mei-Hua Chen, Chia-Yen Cohen, Bruce M. Spencer, Kevin M. Levy, Deborah L. Oenguer, Dost Smoller, Jordan W. TI Genomewide Association Analyses of Electrophysiological Endophenotypes for Schizophrenia and Psychotic Bipolar Disorders: A Preliminary Report SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; bipolar disorders; event-related potentials; genowide assoication; polygentic risk score; endophenotypes ID EVENT-RELATED POTENTIALS; GAMMA OSCILLATIONS; P50 SUPPRESSION; AUDITORY P300; RISK; LINKAGE; FAMILY; METAANALYSIS; FREQUENCY; RELATIVES AB Several event-related potentials (ERP), including P3, sensory gating (P50), and gamma oscillation, are robustly impaired in patients with schizophrenia (SCZ) and bipolar disorder (BIP). Although these ERPs are known to be heritable, little is known about the specific genetic loci involved and the degree to which they overlap with loci influencing mood and psychotic disorders. In the present study, we conducted GWAS to a) identify common variants associated with ERP endophenotypes, and b) construct polygenic risk scores (PRS) to examine overlap between genetic components of ERPs and mood and psychotic disorders. The sample consisted of 271 patients with SCZ or psychotic BIP diagnosis and 128 controls for whom ERP and genomewide data were available. GWAS were conducted using the full sample. PRS, derived from the Psychiatric Genomics Consortium (PGC) analyses of SCZ, BIP, and major depressive disorder were applied to each ERP phenotype. We identified a region on chromosome 14 that was significantly associated with sensory gating (peak SNP rs10132223, P=1.27x10(-9)). This locus has not been previously associated with psychotic illness in PGC-GWAS. In the PRS analyses, patients with a higher load of SCZ risk alleles had reduced gamma response whereas patients with a higher load of BIP risk alleles had smaller P3 amplitude. We observed a genomewide significant locus on chromosome 14 for P50. This locus may influence P50 but not psychotic illness. Among patients with psychotic illness, PRS results indicated genetic overlap between SCZ loci and gamma oscillation and between BIP loci and P3 amplitude. (c) 2015 Wiley Periodicals, Inc. C1 [Hall, Mei-Hua; Levy, Deborah L.; Oenguer, Dost] Harvard Univ, Sch Med, Dept Psychiat, Psychot Disorders Div,McLean Hosp, Boston, MA 02115 USA. [Hall, Mei-Hua] Harvard Univ, Sch Med, Dept Psychiat, Psychosis Neurobiol Lab,McLean Hosp, Boston, MA 02115 USA. [Hall, Mei-Hua; Chen, Chia-Yen; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Cohen, Bruce M.] Harvard Univ, Sch Med, McLean Hosp, Program Neuropsychiat Res, Boston, MA USA. [Levy, Deborah L.] Harvard Univ, Sch Med, Dept Psychiat, Psychol Res Lab,McLean Hosp, Boston, MA 02115 USA. [Chen, Chia-Yen] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Smoller, Jordan W.] Broad Inst, Stanley Ctr Psychiat Res, Boston, MA USA. [Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Hall, MH (reprint author), Harvard Univ, McLean Hosp, Sch Med, Psychosis Neurobiol Lab, Mailstop 223,115 Mill St, Belmont, MA 02478 USA. EM mhall@mclean.harvard.edu FU National Institute of Mental Health [1K01MH086714]; Brain and Behavior Research Foundation; National Alliance for Research on Schizophrenia and Depression [K24MH094614]; Ellison Foundation; Anonymous Foundation FX Grant sponsor: National Institute of Mental Health; Grant number: 1K01MH086714; Grant sponsor: Brain and Behavior Research Foundation; Grant sponsor: National Alliance for Research on Schizophrenia and Depression; Grant number: K24MH094614; Grant sponsor: Ellison Foundation and Anonymous Foundation. NR 55 TC 5 Z9 5 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR PY 2015 VL 168 IS 3 BP 151 EP 161 DI 10.1002/ajmg.b.32298 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA CE8RF UT WOS:000352111100001 PM 25740047 ER PT J AU Bhela, S Mulik, S Gimenez, F Reddy, PBJ Richardson, RL Varanasi, SK Jaggi, U Xu, J Lu, PY Rouse, BT AF Bhela, Siddheshvar Mulik, Sachin Gimenez, Fernanda Reddy, Pradeep B. J. Richardson, Raphael L. Varanasi, Siva Karthik Jaggi, Ujjaldeep Xu, John Lu, Patrick Y. Rouse, Barry T. TI Role of miR-155 in the Pathogenesis of Herpetic Stromal Keratitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID T-CELL RESPONSES; RECEPTOR-BETA CHAIN; SIMPLEX-VIRUS; GENE-EXPRESSION; IFN-GAMMA; CORNEAL NEOVASCULARIZATION; OCULAR INFECTION; TH17 CELLS; MICRORNA-155; INFLAMMATION AB Ocular infection with herpes simplex virus 1 can result in a chronic immunoinflammatory stromal keratitis (SK) lesion that is a significant cause of human blindness. A key to controlling SK Lesion severity is to identify cellular and molecular events responsible for tissue damage and to manipulate them therapeutically. Potential targets for therapy are miRNAs, but these are minimally explored especially in responses to infection. Here, we demonstrated that Mir155 expression was up-regulated after ocular herpes simplex virus 1 infection, with the increased Mir155 expression occurring mainly in macrophages and CD4(+) T cells and to a lesser extent in neutrophils. In vivo studies indicated that Mir155 knockout mice were more resistant to herpes SK with marked suppression of T helper cells type 1 and 17 responses both in the ocular lesions and the lymphoid organs. The reduced SK lesion severity was reflected by increased phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 and interferon-gamma receptor alpha-chain levels in activated CD4(+) T cells in the lymph nodes. Finally, in vivo silencing of miR-155 by the provision of antagomir-155 nanoparticles to herpes simplex virus 1 infected mice led to diminished SK lesions and corneal vascularization. In conclusion, our results indicate that miR-155 contributes to the pathogenesis of SK and represents a promising target to control SK severity. C1 [Bhela, Siddheshvar; Mulik, Sachin; Gimenez, Fernanda; Reddy, Pradeep B. J.; Richardson, Raphael L.; Jaggi, Ujjaldeep; Rouse, Barry T.] Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, Knoxville, TN 37996 USA. [Varanasi, Siva Karthik] Univ Tennessee, Dept Genome Sci & Technol, Knoxville, TN 37996 USA. [Mulik, Sachin] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. [Mulik, Sachin] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [Reddy, Pradeep B. J.] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Xu, John; Lu, Patrick Y.] Sirnaomics Inc, Gaithersburg, MD USA. RP Rouse, BT (reprint author), Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, 1414 Cumberland Ave, Knoxville, TN 37996 USA. EM btr@utk.edu FU NIH National Institute of Allergy and Infectious Diseases [AI 063365]; NIH National Eye Institute [EY 005093] FX Supported by NIH National Institute of Allergy and Infectious Diseases grant AI 063365 and NIH National Eye Institute grant EY 005093 (B.T.R). NR 48 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2015 VL 185 IS 4 BP 1073 EP 1084 DI 10.1016/j.ajpath.2014.12.021 PG 12 WC Pathology SC Pathology GA CE4FX UT WOS:000351787600017 PM 25700796 ER PT J AU DeSilva, JM Bonne-Annee, R Swanson, Z Gill, CM Sobel, M Uy, J Gill, SV AF DeSilva, J. M. Bonne-Annee, R. Swanson, Z. Gill, C. M. Sobel, M. Uy, J. Gill, S., V TI Midtarsal Break Variation in Modern Humans: Functional Causes, Skeletal Correlates, and Paleontological Implications SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE midfoot; Australopithecus; fourth metatarsal; pronation; arch ID BRIEF COMMUNICATION; MIDFOOT BREAK; HUMAN FOOT; CHILDREN; JOINT; BIOMECHANICS; WALKING; GAIT; ADAPTATION; METATARSAL AB The midtarsal break was once treated as a dichotomous, non-overlapping trait present in the foot of non-human primates and absent in humans. Recent work indicates that there is considerable variation in human midfoot dorsiflexion, with some overlap with the ape foot. These findings have called into question the uniqueness of the human lateral midfoot, and the use of osteological features in fossil hominins to characterize the midfoot of our extinct ancestors. Here, we present data on plantar pressure and pedal mechanics in a large sample of adults and children (n=671) to test functional hypotheses concerning variation in midfoot flexibility. Lateral midfoot peak plantar pressure correlates with both sagittal plane flexion at the lateral tarsometatarsal joint, and dorsiflexion at the hallucal metatarsophalangeal joint. The latter finding suggests that midfoot laxity may compromise hallucal propulsion. Multiple regression statistics indicate that a low arch and pronation of the foot explain 40% of variation in midfoot peak plantar pressure, independent of age and BMI. MRI scans on a small subset of study participants (n=19) reveals that curvature of the base of the 4th metatarsal correlates with lateral midfoot plantar pressure and that specific anatomies of foot bones do indeed reflect relative midfoot flexibility. However, while the shape of the base of the 4th metatarsal may reliably reflect midfoot mobility in individual hominins, given the wide range of overlapping variation in midfoot flexibility in both apes and humans, we caution against generalizing foot function in extinct hominin species until larger fossils samples are available. Am J Phys Anthropol 156:543-552, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [DeSilva, J. M.; Bonne-Annee, R.; Swanson, Z.; Gill, C. M.; Sobel, M.; Uy, J.] Boston Univ, Dept Anthropol, Boston, MA 02215 USA. [Gill, C. M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gill, C. M.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Gill, C. M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sobel, M.; Uy, J.] Univ Wisconsin, Dept Anthropol, Madison, WI 53706 USA. [Gill, S., V] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. [Gill, S., V] Boston Univ, Program Rehabil Sci PhD, Boston, MA 02215 USA. [Gill, S., V] Boston Univ, Dept Med, Boston, MA 02118 USA. [Gill, S., V] Boston Univ, Undergrad Program Neurosci, Boston, MA 02215 USA. [Gill, S., V] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. RP DeSilva, JM (reprint author), Boston Univ, Dept Anthropol, 232 Bay State Rd,104B, Boston, MA 02215 USA. EM jdesilva@bu.edu NR 46 TC 8 Z9 8 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 EI 1096-8644 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD APR PY 2015 VL 156 IS 4 SI SI BP 543 EP 552 DI 10.1002/ajpa.22699 PG 10 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA CE2BR UT WOS:000351618300006 PM 25594359 ER PT J AU Salmon, AB Lerner, C Ikeno, Y Perrine, SMM McCarter, R Sell, C AF Salmon, Adam B. Lerner, Chad Ikeno, Yuji Perrine, Susan M. Motch McCarter, Roger Sell, Christian TI Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin-like growth factor I; insulin; metabolism; obesity; gluconeogenesis ID GROWTH-FACTOR-I; DIET-INDUCED OBESITY; HIGH-FAT DIET; HEPATIC INSULIN-RESISTANCE; PROTEIN-1 TRANSGENIC MICE; EXTENDS LIFE-SPAN; ISLET-CELL GROWTH; ADIPOSE-TISSUE; GLUCOSE-INTOLERANCE; A DEFICIENCY AB The extension of lifespan due to reduced insulin-like growth factor 1 (IGF-I) signaling in mice has been proposed to be mediated through alterations in metabolism. Previously, we showed that mice homozygous for an insertion in the Igf1 allele have reduced levels of IGF-I, are smaller, and have an extension of maximum lifespan. Here, we tested whether this specific reduction of IGF-I alters glucose metabolism both on normal rodent chow and in response to high-fat feeding. We found that female IGF-I-deficient mice were lean on a standard rodent diet but paradoxically displayed an insulin-resistant phenotype. However, these mice gained significantly less weight than normal controls when placed on a high-fat diet. In control animals, insulin response was significantly impaired by high-fat feeding, whereas IGF-I-deficient mice showed a much smaller shift in insulin response after high-fat feeding. Gluconeogenesis was also elevated in the IGF-I-deficient mice relative to controls on both normal and high-fat diet. An analysis of metabolism and respiratory quotient over 24 h indicated that the IGF-I-deficient mice preferentially utilized fatty acids as an energy source when placed on a high-fat diet. These results indicate that reduction in the circulating and tissue IGF-I levels can produce a metabolic phenotype in female mice that increases peripheral insulin resistance but renders animals resistant to the deleterious effects of high-fat feeding. C1 [Salmon, Adam B.; Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Salmon, Adam B.; Ikeno, Yuji] Audie L Murphy Vet Affairs Hosp, South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Lerner, Chad; Sell, Christian] Drexel Univ, Coll Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Perrine, Susan M. Motch] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. [McCarter, Roger] Penn State Univ, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. RP Salmon, AB (reprint author), Univ Texas Hlth Sci, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM salmona@uthscsa.edu OI Salmon, Adam/0000-0002-1475-7843 FU National Institutes of Health Training Grant [T32-AG021890-05]; National Institute on Aging [AG-223343]; Drexel University Aging Initiative [AG-02243]; Geriatric Research, Education, and Clinical Center of the South Texas Health Care System; American Federation of Aging Research FX This work was supported by National Institutes of Health Training Grant T32-AG021890-05, Grant No. AG-223343 from the National Institute on Aging, funds from the Drexel University Aging Initiative, and Grant No. AG-02243 to C. Sell. A. B. Salmon was supported by the the Geriatric Research, Education, and Clinical Center of the South Texas Health Care System and a grant from the American Federation of Aging Research. NR 51 TC 3 Z9 3 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR 1 PY 2015 VL 308 IS 7 BP E545 EP E553 DI 10.1152/ajpendo.00558.2014 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA CE9WO UT WOS:000352194300001 PM 25648834 ER PT J AU Kohli, M Dreyer, KJ Geis, JR AF Kohli, Marc Dreyer, Keith J. Geis, J. Raymond TI Rethinking Radiology Informatics SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE data science; decision support; future of radiology; imaging informatics; informatics; radiology work flow ID PHYSICIAN ORDER ENTRY; COMMUNICATION-SYSTEM; MANAGEMENT; COMMON AB OBJECTIVE. Informatics innovations of the past 30 years have improved radiology quality and efficiency immensely. Radiologists are groundbreaking leaders in clinical information technology (IT), and often radiologists and imaging informaticists created, specified, and implemented these technologies, while also carrying the ongoing burdens of training, maintenance, support, and operation of these IT solutions. Being pioneers of clinical IT had advantages of local radiology control and radiology-centric products and services. As health care businesses become more clinically IT savvy, however, they are standardizing IT products and procedures across the enterprise, resulting in the loss of radiologists' local control and flexibility. Although this inevitable consequence may provide new opportunities in the long run, several questions arise. CONCLUSION. What will happen to the informatics expertise within the radiology domain? Will radiology's current and future concerns be heard and their needs addressed? What should radiologists do to understand, obtain, and use informatics products to maximize efficiency and provide the most value and quality for patients and the greater health care community? This article will propose some insights and considerations as we rethink radiology informatics. C1 [Kohli, Marc] Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. [Dreyer, Keith J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Geis, J. Raymond] Univ Colorado, Denver Sch Med, Dept Diagnost Radiol, Ft Collins, CO 80524 USA. RP Geis, JR (reprint author), Univ Colorado, Denver Sch Med, Dept Diagnost Radiol, 3401 Shore Rd, Ft Collins, CO 80524 USA. EM raym.geis@gmail.com NR 18 TC 3 Z9 3 U1 1 U2 8 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2015 VL 204 IS 4 BP 716 EP 720 DI 10.2214/AJR.14.13840 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2AN UT WOS:000351614700024 PM 25794061 ER EF