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, Emer