FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chatterjee, A Oh, DJ Kang, MH Rhee, DJ AF Chatterjee, Ayan Oh, Dong-Jin Kang, Min Hyung Rhee, Douglas J. TI Central corneal thickness does not correlate with TonoLab-measured IOP in several mouse strains with single transgenic mutations of matricellular proteins SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE glaucoma; trabecular meshwork; central corneal thickness; intraocular pressure; rebound tonometry; TonoLab; transgenic mice ID OPTICAL COHERENCE TOMOGRAPHY; LOWER INTRAOCULAR-PRESSURES; OPEN-ANGLE GLAUCOMA; NONINVASIVE MEASUREMENT; TRABECULAR MESHWORK; REBOUND TONOMETRY; MICE; GOLDMANN; THROMBOSPONDIN-1; SPARC AB Accurate and reliable measurement of intraocular pressure (lOP) is crucial in the study of glaucoma using the mouse model. The purpose of this study was to determine the relationship between TonoLabmeasured IOP and central corneal thickness (CCT) in mouse strains with single gene mutations of matricellular proteins. Wild-type (WT) and transgenic mouse strains with single gene mutations (KO) of thrombospondin-1 (TSP-1), thrombospondin-2 (TSP-2), osteopontin (OPN), hevin, and secreted protein acidic rich in cysteine (SPARC) were imaged at six weeks using optical coherence tomography (Stratus, Zeiss) to determine CCT. LOP was measured between llam and 3pm using TonoLab, one week later. For all measurements, mice were anesthetized using intraperitoneal injection ketamine:xylazine. CCT and IOP were measured in 583 mice (TSP-1 n = 71 and 41, TSP-2 n = 60 and 32, OPN n = 81 and 50, hevin n = 59 and 76, SPARC n = 54 and 59, WT and KO, respectively). Mean CCT was 5-6% lower in three KO strains TSP-1, OPN, and SPARC-compared to their corresponding WT (p = 1.55 x 10(-7), 1.63 x 10(-11), and 1.91 x 10(-7), respectively). The mean IOP was 8.3%, 6.6%, and 15.1% lower in three KO strains TSP-1, TSP-2, and SPARC-compared to corresponding WT (p = 2.11 x 10(-5)., 2.93 x 10(-3), and 3.76 x 10(-9), respectively. Linear regression of BP versus CCT yielded no statistically significant within-strain correlations for TSP-1 (p = 0.12 and 0.073), TSP-2 (p = 0.473 and 0.92), OPN (p = 0.212 and 0.916), Hevin (p = 0.746 and 0.257), and SPARC (p = 0.080 and 0.056), reported as p-values considering a null hypothesis of zero slope (WT and KO, respectively). Neither C57-derived strains (TSP-1 and OPN) nor 129-derived strains (TSP-2, hevin, SPARC) demonstrated a correlation between mean MP and mean CCT across different strains (p = 0.75 and p = 0.53, respectively). Taken together, these results indicate that CCT is not required to interpret TonoLab IOP readings in the mice when CCT varies 10% about the mean. This does not exclude the possibility of an IOP-CCT correlation for CCT values outside this range or for interstrain comparisons where the mean CCT differs more than 10%. 2013 Elsevier Ltd. All rights reserved. C1 [Chatterjee, Ayan; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU Howard Hughes Medical Institute; Massachusetts Lions Research Foundation; NIH [R01 BY 019654-01, EY 014104] FX Funding Supported by Howard Hughes Medical Institute Student Research Fellowship, Massachusetts Lions Research Foundation, NIH R01 BY 019654-01 (DJR), and NIH EY 014104 (MEEI Vision-Core Grant). NR 35 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2013 VL 115 BP 106 EP 112 DI 10.1016/j.exer.2013.06.017 PG 7 WC Ophthalmology SC Ophthalmology GA 239XZ UT WOS:000326060600014 PM 23806329 ER PT J AU Lin, PY Chen, JJJ Lin, SI AF Lin, Pei-Yi Chen, Jia-Jin Jason Lin, Sang-I TI The cortical control of cycling exercise in stroke patients: An fNIRS study SO HUMAN BRAIN MAPPING LA English DT Article DE stroke; near-infrared spectroscopy; cycling; brain activation; rehabilitation ID NEAR-INFRARED SPECTROSCOPY; PREMOTOR CORTEX; MOTOR REHABILITATION; EXTRINSIC FEEDBACK; HEMIPARETIC STROKE; PEDALING EXERCISE; VISUAL FEEDBACK; ACTIVATION; GAIT; MOVEMENT AB Stroke survivors suffering from deficits in motor control typically have limited functional abilities, which could result in poor quality of life. Cycling exercise is a common training paradigm for restoring locomotion rhythm in patients. The provision of speed feedback has been used to facilitate the learning of controlled cycling performance and the neuromuscular control of the affected leg. However, the central mechanism for motor relearning of active and passive pedaling motions in stroke patients has not been investigated as extensively. The aim of this study was to measure the cortical activation patterns during active cycling with and without speed feedback and during power-assisted (passive) cycling in stroke patients. A frequency-domain near-infrared spectroscopy (FD-NIRS) system was used to detect the hemodynamic changes resulting from neuronal activity during the pedaling exercise from the bilateral sensorimotor cortices (SMCs), supplementary motor areas (SMAs), and premotor cortices (PMCs). The variation in cycling speed and the level of symmetry of muscle activation of bilateral rectus femoris were used to evaluate cycling performance. The results showed that passive cycling had a similar cortical activation pattern to that observed during active cycling without feedback but with a smaller intensity of the SMC of the unaffected hemisphere. Enhanced PMC activation of the unaffected side with improved cycling performance was observed during active cycling with feedback, with respect to that observed without feedback. This suggests that the speed feedback enhanced the PMC activation and improved cycling performance in stroke patients. Hum Brain Mapp 34:2381-2390, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Lin, Pei-Yi; Chen, Jia-Jin Jason] Natl Cheng Kung Univ, Dept Biomed Engn, Tainan 70101, Taiwan. [Lin, Pei-Yi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Opt Div,Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Chen, Jia-Jin Jason] Natl Cheng Kung Univ, Med Device Innovat Ctr, Tainan 70101, Taiwan. [Lin, Sang-I] Natl Cheng Kung Univ, Dept Phys Therapy, Tainan 70101, Taiwan. [Lin, Sang-I] Natl Cheng Kung Univ, Inst Allied Hlth Sci, Tainan 70101, Taiwan. RP Lin, SI (reprint author), Natl Cheng Kung Univ, Dept Phys Therapy, 1 Univ Rd, Tainan 70101, Taiwan. EM lin31@mail.ncku.edu.tw FU National Health Research Institute [NHRI-EX97-9734EI]; National Science council of Republic of China [NSC-98-2221-E006-010, NSC 100-2321-B-006-018] FX Contract grant sponsor: National Health Research Institute; Contract grant number: NHRI-EX97-9734EI; Contract grant sponsor: National Science council of Republic of China; Contract grant numbers: NSC-98-2221-E006-010, NSC 100-2321-B-006-018. NR 51 TC 12 Z9 12 U1 2 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2013 VL 34 IS 10 BP 2381 EP 2390 DI 10.1002/hbm.22072 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 216TI UT WOS:000324306900002 PM 22461337 ER PT J AU Napadow, V Lee, J Kim, J Cina, S Maeda, Y Barbieri, R Harris, RE Kettner, N Park, K AF Napadow, Vitaly Lee, Jeungchan Kim, Jieun Cina, Stephen Maeda, Yumi Barbieri, Riccardo Harris, Richard E. Kettner, Norman Park, Kyungmo TI Brain correlates of phasic autonomic response to acupuncture stimulation: An event-related fMRI study SO HUMAN BRAIN MAPPING LA English DT Article DE orienting response; defense response; acupoint; skin conductance response; heart rate ID SYMPATHETIC-NERVE ACTIVITY; HEART-RATE; MANUAL ACUPUNCTURE; STIMULUS-INTENSITY; HUMANS; MOTION; PAIN; IMPLEMENTATION; DYNAMICS; REFLEX AB Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR-) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR- was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR-. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR-, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli. Hum Brain Mapp 34:2592-2606, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Napadow, Vitaly; Lee, Jeungchan; Kim, Jieun; Cina, Stephen; Maeda, Yumi] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, Vitaly; Maeda, Yumi; Kettner, Norman] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Lee, Jeungchan; Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, 149 13th St 2301, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu; saenim@khu.ac.kr OI LEE, JEUNGCHAN/0000-0002-4424-175X; Barbieri, Riccardo/0000-0001-9381-3833 FU National Center for Complementary and Alternative Medicine, NIH [K01-AT002166, R01-AT004714, P01-AT002048, F05-AT003770, R01 HL084502]; NCRR [P41-RR14075, UL1-RR025758]; Institute of Information Technology Advancement, Korea [KOSEF-2009-0076345, IITA-2008-(C1090-0801-0002)]; Department of Army grant DAMD [W81XWH-07-2-0050]; Dana Foundation Award in Brain and Immuno-imaging, Mental Illness and Neuroscience Discovery (MIND) FX Contract grant sponsors: National Center for Complementary and Alternative Medicine, NIH; K01-AT002166, R01-AT004714, P01-AT002048, F05-AT003770; R01 HL084502; Contract grant sponsor: NCRR; Contract grant number: P41-RR14075, UL1-RR025758; Institute; Institute of Information Technology Advancement, Korea and KOSEF-2009-0076345; Contract grant number: IITA-2008-(C1090-0801-0002); Contract grant sponsor: Department of Army grant DAMD-Award Number; Contract grant number: W81XWH-07-2-0050; Contract grant sponsor: Dana Foundation Award in Brain and Immuno-imaging, Mental Illness and Neuroscience Discovery (MIND). NR 69 TC 21 Z9 21 U1 3 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2013 VL 34 IS 10 BP 2592 EP 2606 DI 10.1002/hbm.22091 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 216TI UT WOS:000324306900018 PM 22504841 ER PT J AU Sitek, A Moore, SC AF Sitek, Arkadiusz Moore, Stephen C. TI Evaluation of Imaging Systems Using the Posterior Variance of Emission Counts SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Bayes methods; design optimization; Monte Carlo methods; positron emission tomography; single-photon emission computed tomography ID BEAM RANGE VERIFICATION; MAXIMUM-LIKELIHOOD; TRANSMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; PROTON THERAPY; SINGLE-PHOTON; EM ALGORITHM; RECONSTRUCTION; SPECT; NUMBER AB We investigate an approach to evaluation of emission-tomography (ET) imaging systems used for region-of-interest (ROI) estimation tasks. In the evaluation we employ the concept of "emission counts" (EC), which are the number of events per voxel emitted during a scan. We use the reduction in posterior variance of ROI EC, compared to the prior ROI EC variance, as the metric of primary interest, which we call the "posterior variance reduction index" (PVRI). Systems that achieve a higher PVRI are considered superior to systems with lower PVRI. The approach is independent of the reconstruction method and is applicable to all photon-limited data types including list-mode data. We analyzed this approach using a model of 2-D tomography, and compared our results to the classical theory of tomographic sampling. We found that performance evaluations using the PVRI index were consistent with the classical theory. System evaluation based on EC posterior variance is an intuitively appealing and physically meaningful method that is useful for evaluation of system performance in ROI quantitation tasks. C1 [Sitek, Arkadiusz; Moore, Stephen C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sitek, Arkadiusz; Moore, Stephen C.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Sitek, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sarkadiu@gmail.com; scmoore@bwh.harvard.edu OI Sitek, Arkadiusz/0000-0002-0677-4002 FU National Institutes of Health [R21 CA123057, R01 EB001989, R01 EB 000802] FX This work was supported in part by the National Institutes of Health under Grant R21 CA123057, Grant R01 EB001989, and Grant R01 EB 000802. NR 31 TC 6 Z9 6 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2013 VL 32 IS 10 BP 1829 EP 1839 DI 10.1109/TMI.2013.2265886 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 230YV UT WOS:000325380300007 PM 23744672 ER PT J AU Abazeed, M Adams, D Hurov, K Tamayo, P Creighton, C Sonkin, D Giacomelli, A Schreiber, S Hammerman, P Meyerson, M AF Abazeed, M. Adams, D. Hurov, K. Tamayo, P. Creighton, C. Sonkin, D. Giacomelli, A. Schreiber, S. Hammerman, P. Meyerson, M. TI Integrative Radiogenomic Profiling of Squamous Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Abazeed, M.] Harvard Radiat Oncol Program, Boston, MA USA. [Adams, D.; Tamayo, P.] Broad Inst, Cambridge, MA USA. [Hurov, K.; Sonkin, D.] Novartis Inst Biomed Res, Cambridge, MA USA. [Creighton, C.] Baylor Coll Med, Houston, MA USA. [Giacomelli, A.] Harvard Univ, Sch Med, Boston, MA USA. [Schreiber, S.] Howard Hughes Med Inst, Cambridge, MA USA. [Hammerman, P.; Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S138 EP S139 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600341 ER PT J AU Aizer, AA Shih, HA Loeffler, JS Oh, KS AF Aizer, A. A. Shih, H. A. Loeffler, J. S. Oh, K. S. TI Adjuvant Radiation Therapy Is Associated With Survival Benefit in WHO Grade 3 Astrocytomas But Not Oligodendrogliomas: Results From a Population-Based Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Aizer, A. A.] Harvard Radiat Oncol Program, Boston, MA USA. [Shih, H. A.; Loeffler, J. S.; Oh, K. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S256 EP S256 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601055 ER PT J AU Arvold, ND Heidari, P Kunawudhi, A Sequist, LV Mahmood, U AF Arvold, N. D. Heidari, P. Kunawudhi, A. Sequist, L. V. Mahmood, U. TI FMISO-PET as Biomarker of Early Response to Targeted Therapy in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Arvold, N. D.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Heidari, P.; Kunawudhi, A.; Sequist, L. V.; Mahmood, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S645 EP S646 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602356 ER PT J AU Arvold, ND Wen, PY Reardon, DA Lee, EQ Pinnell, NE Christianson, LW Weiss, SE Dunn, IF Ligon, KL Alexander, BM AF Arvold, N. D. Wen, P. Y. Reardon, D. A. Lee, E. Q. Pinnell, N. E. Christianson, L. W. Weiss, S. E. Dunn, I. F. Ligon, K. L. Alexander, B. M. TI Disconnect Between Recurrence-Free Survival and Overall Survival for Newly Diagnosed Glioblastoma Patients Receiving Adjuvant Bevacizumab SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Arvold, N. D.; Wen, P. Y.; Reardon, D. A.; Lee, E. Q.; Pinnell, N. E.; Christianson, L. W.; Dunn, I. F.; Ligon, K. L.; Alexander, B. M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Weiss, S. E.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S17 EP S17 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600040 ER PT J AU Bekelman, JE Wall, T Nassif, D Mojarrad, M Fraass, B Lawton, C Rose, C Zietman, A Efstathiou, J AF Bekelman, J. E. Wall, T. Nassif, D. Mojarrad, M. Fraass, B. Lawton, C. Rose, C. Zietman, A. Efstathiou, J. CA NROR TI The National Radiation Oncology Registry: Approaches to Regulatory Compliance to Promote Wide Participation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Bekelman, J. E.] Univ Penn, Philadelphia, PA 19104 USA. [Wall, T.] St Lukes Hosp, Kansas City, KS USA. [Nassif, D.; Zietman, A.; Efstathiou, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mojarrad, M.] Radiat Oncol Inst, Fairfax, VA USA. [Fraass, B.] Cedars Sinai, Los Angeles, CA USA. [Lawton, C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rose, C.] Vantage Oncol, Beverly Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S493 EP S493 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601672 ER PT J AU Bhatt, AD DeLaney, TF Schwab, JH Mullen, JT Liao, EC Ferreira, A Niemierko, A Hornicek, FJ Chen, YE AF Bhatt, A. D. DeLaney, T. F. Schwab, J. H. Mullen, J. T. Liao, E. C. Ferreira, A. Niemierko, A. Hornicek, F. J. Chen, Y. E. TI Reduction in Wound Complications With Low- Versus High-Dose Preoperative Radiation Therapy for Sacro-Coccygeal Chordomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Bhatt, A. D.; DeLaney, T. F.; Schwab, J. H.; Mullen, J. T.; Liao, E. C.; Ferreira, A.; Niemierko, A.; Hornicek, F. J.; Chen, Y. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S166 EP S167 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600412 ER PT J AU Cai, S Hong, TS Goldberg, SI Fernandez-del Castillo, C Thayer, SP Ferrone, CR Ryan, DP Willett, CG Warshaw, AL Wo, JY AF Cai, S. Hong, T. S. Goldberg, S. I. Fernandez-del Castillo, C. Thayer, S. P. Ferrone, C. R. Ryan, D. P. Willett, C. G. Warshaw, A. L. Wo, J. Y. TI Long-term Outcomes and Prognostic Factors for Locally-Advanced Pancreatic Cancer Patients Treated With Intraoperative Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Cai, S.] Harvard Univ, Sch Med, Boston, MA USA. [Hong, T. S.; Goldberg, S. I.; Fernandez-del Castillo, C.; Thayer, S. P.; Ferrone, C. R.; Ryan, D. P.; Warshaw, A. L.; Wo, J. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Willett, C. G.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S303 EP S304 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601181 ER PT J AU Clayman, RH Gierga, DP Dryden-Peterson, S Russell, A Bruce, K Paly, J Mmalane, M Bvochora, M Kasese, J Efstathiou, JA AF Clayman, R. H. Gierga, D. P. Dryden-Peterson, S. Russell, A. Bruce, K. Paly, J. Mmalane, M. Bvochora, M. Kasese, J. Efstathiou, J. A. TI Addressing the Growing Cancer Burden in the Wake of the AIDS Epidemic in Botswana: A Collaborative Partnership SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Clayman, R. H.; Gierga, D. P.; Dryden-Peterson, S.; Russell, A.; Bruce, K.; Paly, J.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mmalane, M.] Botswana Harvard Partnership, Gaborone, Botswana. [Bvochora, M.] Gaborone Private Hosp, Gaborone, Botswana. [Kasese, J.] Bokamoso Private Hosp, Gaborone, Botswana. 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S488 EP S488 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601659 ER PT J AU Clayman, RH Shipley, WU Galland-Girodet, S Niemierko, A Gray, PJ Paly, J Heney, N Kaufman, DS Zietman, A Efstathiou, JA AF Clayman, R. H. Shipley, W. U. Galland-Girodet, S. Niemierko, A. Gray, P. J. Paly, J. Heney, N. Kaufman, D. S. Zietman, A. Efstathiou, J. A. TI Outcomes of Selective Bladder Preservation in the Elderly Treated With Conservative Surgery and Chemoradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Clayman, R. H.; Shipley, W. U.; Galland-Girodet, S.; Niemierko, A.; Gray, P. J.; Paly, J.; Heney, N.; Kaufman, D. S.; Zietman, A.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S83 EP S83 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600203 ER PT J AU Efstathiou, JA Nassif, D Lawton, C Zietman, A Sandler, H Michalski, J Gabriel, P McNutt, T Bekelman, J AF Efstathiou, J. A. Nassif, D. Lawton, C. Zietman, A. Sandler, H. Michalski, J. Gabriel, P. McNutt, T. Bekelman, J. CA NROR TI Practice-Based Evidence to Evidence-Based Practice: Initial Challenges in Building the NROR SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Efstathiou, J. A.; Nassif, D.; Zietman, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lawton, C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Sandler, H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Michalski, J.] Washington Univ, Sch Med, St Louis, MO USA. [Gabriel, P.; Bekelman, J.; NROR] Univ Penn, Philadelphia, PA 19104 USA. [McNutt, T.] Johns Hopkins Univ, Sch Med, Baltimore, MD 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S494 EP S495 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601676 ER PT J AU Galland, S Clayman, RH Zietman, AL Shipley, WU Russell, AH Heney, NM Kaufman, DS Whu, C Gakis, G Efstathiou, JA AF Galland, S. Clayman, R. H. Zietman, A. L. Shipley, W. U. Russell, A. H. Heney, N. M. Kaufman, D. S. Whu, C. Gakis, G. Efstathiou, J. A. TI Multimodality Management in Primary Urethral Cancer: The Role of Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Galland, S.; Clayman, R. H.; Zietman, A. L.; Shipley, W. U.; Russell, A. H.; Heney, N. M.; Kaufman, D. S.; Whu, C.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gakis, G.] Univ Tubingen Hosp, Tubingen, Germany. 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S402 EP S402 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601433 ER PT J AU Galland, S Sadek, BT Shenouda, MN Abi-Raad, RF Keruakous, AR Golberg, S MacDonald, S Taghian, A AF Galland, S. Sadek, B. T. Shenouda, M. N. Abi-Raad, R. F. Keruakous, A. R. Golberg, S. MacDonald, S. Taghian, A. TI Long-term Outcomes in Breast Cancer Patients With 10 or More Positive Axillary Nodes: Is Conservative Treatment an Optimal Option? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Galland, S.; Sadek, B. T.; Shenouda, M. N.; Abi-Raad, R. F.; Keruakous, A. R.; Golberg, S.; MacDonald, S.; Taghian, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S236 EP S236 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601005 ER PT J AU Galland, S Pashtan, IM MacDonald, SM Ancukiewicz, M Specht, M Gadd, MA Smith, BL Recht, A Taghian, AG AF Galland, S. Pashtan, I. M. MacDonald, S. M. Ancukiewicz, M. Specht, M. Gadd, M. A. Smith, B. L. Recht, A. Taghian, A. G. TI Long-term Cosmetic Outcomes and Toxicities of Proton Compared to Photon 3D-Conformal Accelerated Partial Breast Irradiation (3D-APBI) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Galland, S.; Pashtan, I. M.; MacDonald, S. M.; Ancukiewicz, M.; Specht, M.; Gadd, M. A.; Smith, B. L.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Recht, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S195 EP S196 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600485 ER PT J AU Gensheimer, MF Hummel-Kramer, SM Cain, D Quang, TS AF Gensheimer, M. F. Hummel-Kramer, S. M. Cain, D. Quang, T. S. TI Simple Rule for Prediction of Parotid Gland Sparing Early in the Radiation Treatment Planning Process SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Gensheimer, M. F.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Hummel-Kramer, S. M.; Cain, D.; Quang, T. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S588 EP S588 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602211 ER PT J AU Gray, PJ Lin, C Shipley, WU Jemal, A Efstathiou, JA AF Gray, P. J. Lin, C. Shipley, W. U. Jemal, A. Efstathiou, J. A. TI Presentation, Treatment, and Outcomes for Bladder Cancer Patients With Nonurothelial Histologies Treated by Radical Cystectomy: Implications for Adjuvant Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Gray, P. J.] Harvard Radiat Oncol Program, Boston, MA USA. [Gray, P. J.; Shipley, W. U.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lin, C.] Amer Canc Soc, Atlanta, GA 30329 USA. [Jemal, A.] Amer Canc Soc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S82 EP S82 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600201 ER PT J AU Greenberger, B Pacold, ME Tay, JJ Alter, R Huang, Q Ge, J Bradner, JE Engelward, BP Yaffe, MB Floyd, SR AF Greenberger, B. Pacold, M. E. Tay, J. J. Alter, R. Huang, Q. Ge, J. Bradner, J. E. Engelward, B. P. Yaffe, M. B. Floyd, S. R. TI Characterizing Cell-Specific Radiation Sensitization Induced by HDAC Inhibition SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Greenberger, B.; Alter, R.; Huang, Q.; Yaffe, M. B.; Floyd, S. R.] Koch Inst Integrat Canc Res, Cambridge, MA USA. [Greenberger, B.] Harvard MIT Hlth Sci & Technol MD Program, Boston, MA USA. [Pacold, M. E.] Whitehead Inst, Cambridge, MA 02142 USA. [Pacold, M. E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Tay, J. J.; Ge, J.; Engelward, B. P.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Tay, J. J.] Agency Sci Technol & Res, Grad Acad, Singapore, Singapore. [Bradner, J. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yaffe, M. B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Floyd, S. R.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S627 EP S628 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602307 ER PT J AU Greenberger, B Pulsifer, MB MacDonald, SM Ebb, DH Huang, MS Marcus, KJ Oberg, J Tarbell, NJ Yock, TI AF Greenberger, B. Pulsifer, M. B. MacDonald, S. M. Ebb, D. H. Huang, M. S. Marcus, K. J. Oberg, J. Tarbell, N. J. Yock, T. I. TI Mature Clinical Outcomes of Proton Radiation for Pediatric Low-Grade Gliomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Greenberger, B.; Tarbell, N. J.] Harvard Univ, Sch Med, Boston, MA USA. [Pulsifer, M. B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [MacDonald, S. M.; Oberg, J.; Tarbell, N. J.; Yock, T. I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ebb, D. H.; Huang, M. S.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Marcus, K. J.] Brigham & Womens Hosp, Dept Radiat Oncol, 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S593 EP S593 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602223 ER PT J AU Halasz, LM Uno, H Zornosa, C D'Amico, TA Dexter, EU Hayman, JA Otterson, GA Pisters, KM Weeks, JC Punglia, RS AF Halasz, L. M. Uno, H. Zornosa, C. D'Amico, T. A. Dexter, E. U. Hayman, J. A. Otterson, G. A. Pisters, K. M. Weeks, J. C. Punglia, R. S. TI Comparative Effectiveness of Stereotactic Radiosurgery (SRS) Versus Whole Brain Radiation Therapy (WBRT) for Patients With Brain Metastases From Non-Small Cell Lung Cancer (NSCLC) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Halasz, L. M.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Uno, H.; Weeks, J. C.; Punglia, R. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zornosa, C.] Natl Comprehens Canc Network, Ft Washington, PA USA. [D'Amico, T. A.] Duke Canc Inst, Durham, NC USA. [Dexter, E. U.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Dexter, E. U.] SUNY Buffalo, Buffalo, NY 14260 USA. [Hayman, J. A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Otterson, G. A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Pisters, K. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S41 EP S41 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600098 ER PT J AU Hong, TS Bosch, WR Crane, CH Dawson, LA AF Hong, T. S. Bosch, W. R. Crane, C. H. Dawson, L. A. TI Interobserver Variability in Target Definition for Hepatocellular Carcinoma (HCC) With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group (RTOG) HCC Consensus Panel SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Hong, T. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bosch, W. R.] Washington Univ, St Louis, MO USA. [Crane, C. H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dawson, L. A.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S28 EP S28 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600066 ER PT J AU Hoopes, DJ Johnstone, PA Chapin, PS Kabban, CMS Lee, WR Chen, AB Fraass, BA Skinner, WJK Marks, LB AF Hoopes, D. J. Johnstone, P. A. Chapin, P. S. Kabban, C. M. Schubert Lee, W. R. Chen, A. B. Fraass, B. A. Skinner, W. J. K. Marks, L. B. TI Early Results From the ASTRO Practice Patterns in Peer Review Survey Project SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Hoopes, D. J.] David Grant Med Ctr, Travis Afb, CA USA. [Johnstone, P. A.] Indiana Univ, Indianapolis, IN 46204 USA. [Chapin, P. S.; Kabban, C. M. Schubert] Air Force Inst Technol, Wright Patterson AFB, OH USA. [Lee, W. R.] Duke Univ, Sch Med, Durham, NC USA. [Chen, A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fraass, B. A.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Skinner, W. J. K.] Walter Reed Bethesda Natl Mil Med, Bethesda, MD USA. [Marks, L. B.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S119 EP S119 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600292 ER PT J AU Hoppe, BS Michalski, JM Mendenhall, NP Morris, CG Henderson, RH Nichols, RC Regan, MM Sandler, HM Sanda, MG Hamstra, DA AF Hoppe, B. S. Michalski, J. M. Mendenhall, N. P. Morris, C. G. Henderson, R. H. Nichols, R. C. Regan, M. M. Sandler, H. M. Sanda, M. G. Hamstra, D. A. TI Comparative Effectiveness Study of Proton Therapy Versus IMRT for Definitive Treatment of Prostate Cancer Based on Patient-Reported Outcomes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Hoppe, B. S.; Mendenhall, N. P.; Morris, C. G.; Henderson, R. H.; Nichols, R. C.] Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. [Michalski, J. M.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Regan, M. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sandler, H. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Sanda, M. G.] Washington Univ, Dept Radiat Oncol, St Louis, MO USA. [Hamstra, D. A.] Univ Michigan, Coll Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RI Sanda, Martin/B-2023-2015 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S346 EP S346 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601289 ER PT J AU Jimenez, RB Trautwein, JA Efstathiou, JA Mitin, T Maheswaran, S Haber, DA Shipley, WU Zietman, AL Wu, CL Miyamoto, DT AF Jimenez, R. B. Trautwein, J. A. Efstathiou, J. A. Mitin, T. Maheswaran, S. Haber, D. A. Shipley, W. U. Zietman, A. L. Wu, C. L. Miyamoto, D. T. TI Feasibility of Gene Expression Signature Analysis in Prostate Cancer Biopsy Specimens to Predict Outcomes Following Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Jimenez, R. B.] Harvard Radiat Oncol Program, Boston, MA USA. [Trautwein, J. A.; Maheswaran, S.; Haber, D. A.; Miyamoto, D. T.] Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA USA. [Efstathiou, J. A.; Mitin, T.; Shipley, W. U.; Zietman, A. L.; Miyamoto, D. T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Wu, C. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S669 EP S669 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602419 ER PT J AU Jimenez, RB Alexander, BM Mahadevan, A Niemierko, A Rajakesari, S Arvold, ND Floyd, S Oh, KS Loeffler, JS Shih, HA AF Jimenez, R. B. Alexander, B. M. Mahadevan, A. Niemierko, A. Rajakesari, S. Arvold, N. D. Floyd, S. Oh, K. S. Loeffler, J. S. Shih, H. A. TI The Impact of Different Hypofractionated Stereotactic Radiation Therapy Regimens for Brain Metastases on Local Control and Toxicity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Jimenez, R. B.] Harvard Radiat Oncol Program, Boston, MA USA. [Alexander, B. M.; Rajakesari, S.; Arvold, N. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mahadevan, A.; Floyd, S.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Niemierko, A.; Oh, K. S.; Loeffler, J. S.; Shih, H. A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S275 EP S275 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601104 ER PT J AU Kamran, SC Collier, JM Lane, A Kim, I Chen, YE MacDonald, SM Munzenrider, JE Gragoudas, E Shih, HA AF Kamran, S. C. Collier, J. M. Lane, A. Kim, I. Chen, Y. E. MacDonald, S. M. Munzenrider, J. E. Gragoudas, E. Shih, H. A. TI Outcomes of Proton Therapy for the Treatment of Uveal Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Kamran, S. C.] Harvard Univ, Sch Med, Boston, MA USA. [Collier, J. M.; Chen, Y. E.; MacDonald, S. M.; Munzenrider, J. E.; Shih, H. A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lane, A.; Kim, I.; Gragoudas, E.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S268 EP S268 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601086 ER PT J AU Keruakous, AR Sadek, BT Shenouda, MN Raad, RFA Niemierko, A Taghian, AG AF Keruakous, A. R. Sadek, B. T. Shenouda, M. N. Raad, R. F. Abi Niemierko, A. Taghian, A. G. TI Outcome of Patients With Breast Cancer Treated With Breast Conserving Treatment or Mastectomy and No Postmastectomy Radiation and With Isolated Tumor Cells SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Keruakous, A. R.; Sadek, B. T.; Shenouda, M. N.; Raad, R. F. Abi; Niemierko, A.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S198 EP S199 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600492 ER PT J AU Kim, M Chen, M de Castro, M Loffredo, M Kantoff, PW D'Amico, AV AF Kim, M. Chen, M. de Castro, M. Loffredo, M. Kantoff, P. W. D'Amico, A. V. TI Defining the Optimal Approach to the Patient With Postradiation Prostate-Specific Antigen Recurrence Using Outcome Data From a Prospective Randomized Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Kim, M.] Harvard Radiat Oncol, Boston, MA USA. [Chen, M.] Univ Connecticut, Hartford, CT 06112 USA. [de Castro, M.] Univ Sao Paulo, Sao Paulo, Brazil. [Loffredo, M.; D'Amico, A. V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kantoff, P. W.] Dana Farber Canc Inst, 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S156 EP S156 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600386 ER PT J AU Korideck, H Ngwa, W Kumar, R Makrigiorgos, M Berbeco, R AF Korideck, H. Ngwa, W. Kumar, R. Makrigiorgos, M. Berbeco, R. TI Dosimetric Verification of the Small Animal Radiation Research Platform (SARRP) Treatment Planning System (TPS) in Mice SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Korideck, H.; Ngwa, W.; Makrigiorgos, M.; Berbeco, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ngwa, W.; Makrigiorgos, M.; Berbeco, R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kumar, R.] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S150 EP S150 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600371 ER PT J AU Kozono, DE Cron, K Kushwaha, D D'Andrea, AD AF Kozono, D. E. Cron, K. Kushwaha, D. D'Andrea, A. D. TI Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Kozono, D. E.; Cron, K.; Kushwaha, D.; D'Andrea, A. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S21 EP S21 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600051 ER PT J AU Krislman, MS Tseng, Y Sullivan, A Jones, J Gorman, D Taylor, A Pacold, M Kalinowski, B Mamon, H Balboni, T AF Krislman, M. S. Tseng, Y. Sullivan, A. Jones, J. Gorman, D. Taylor, A. Pacold, M. Kalinowski, B. Mamon, H. Balboni, T. TI The Supportive and Palliative Radiation Oncology Service: The Impact of a Dedicated Service on Palliative Cancer Care SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Krislman, M. S.; Tseng, Y.] Harvard Radiat Oncol Program, Boston, MA USA. [Sullivan, A.] Harvard Univ, Dept Biostat, Cambridge, MA 02138 USA. [Jones, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gorman, D.; Taylor, A.; Pacold, M.; Kalinowski, B.; Mamon, H.; Balboni, T.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Gorman, D.; Taylor, A.; Pacold, M.; Kalinowski, B.; Mamon, H.; Balboni, T.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S90 EP S91 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600221 ER PT J AU Ladra, M Szymonifka, J MacDonald, SH Yeap, BY Friedmann, AM Kasper, H Mahajan, A Grosshans, D Tarbell, N Yock, TI AF Ladra, M. Szymonifka, J. MacDonald, S. H. Yeap, B. Yong Friedmann, A. M. Kasper, H. Mahajan, A. Grosshans, D. Tarbell, N. Yock, T. I. TI Proton Radiation Therapy for Rhabdomyosarcoma: Preliminary Results From a Multicenter Prospective Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Ladra, M.; Szymonifka, J.; MacDonald, S. H.; Yeap, B. Yong; Friedmann, A. M.; Kasper, H.; Grosshans, D.; Tarbell, N.; Yock, T. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahajan, A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S597 EP S598 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602233 ER PT J AU Laufer, M ter Veer, A Bekaii-Saab, T Engstrom, PF Lai, L Schrag, D Skibber, JM Small, W Wilkinson, N Goodman, KA AF Laufer, M. ter Veer, A. Bekaii-Saab, T. Engstrom, P. F. Lai, L. Schrag, D. Skibber, J. M. Small, W. Wilkinson, N. Goodman, K. A. TI Trends in Intensity Modulated Radiation Therapy Use for Locally-Advanced Rectal Cancer at National Comprehensive Cancer Network (NCCN) Centers SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Laufer, M.; Goodman, K. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [ter Veer, A.; Lai, L.] City Hope Canc Ctr, Duarte, CA USA. [Bekaii-Saab, T.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Cleveland, OH USA. [Bekaii-Saab, T.] Solove Res Inst, Cleveland, OH USA. [Engstrom, P. F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Skibber, J. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Small, W.] Robert H Lurie Comprehens Canc Ctr Chicago, Chicago, IL USA. [Wilkinson, N.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S179 EP S179 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600444 ER PT J AU Lim, K Lee, J Park, Y Park, J Ye, S AF Lim, K. Lee, J. Park, Y. Park, J. Ye, S. TI Dose Verification of 2D and 3D Intrafractional Tumor Motion for Patient-Specific Quality Assurance of Respiratory-Gated Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Lim, K.; Ye, S.] Seoul Natl Univ Hosp, Dept Radiat Oncol, Seoul 110744, South Korea. [Lee, J.; Ye, S.] Seoul Natl Univ, Program Biomed Radiat Sci, Dept Transdisciplinary Studies, Grad Sch Convergence Sci & Technol, Seoul, South Korea. [Park, Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Park, J.] Seoul Natl Univ, Coll Med, Interdisciplinary Program Radiat Appl Life Sci, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S700 EP S700 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602499 ER PT J AU Mak, KS Gainor, JF Niemierko, A Oh, KS Willers, H Choi, NC Loeffler, JS Sequist, LV Shaw, AT Shih, HA AF Mak, K. S. Gainor, J. F. Niemierko, A. Oh, K. S. Willers, H. Choi, N. C. Loeffler, J. S. Sequist, L. V. Shaw, A. T. Shih, H. A. TI Radiation Therapy for Brain Metastases in Non-Small Cell Lung Cancer: Significance of Mutations in EGFR, ALK, or KRAS on Radiation Therapy Response and Survival SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Mak, K. S.] Harvard Radiat Oncol Program, Boston, MA USA. [Mak, K. S.; Gainor, J. F.; Niemierko, A.; Oh, K. S.; Willers, H.; Choi, N. C.; Loeffler, J. S.; Sequist, L. V.; Shaw, A. T.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S51 EP S51 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600123 ER PT J AU Mak, RH Hermann, G Lewis, JH Baldini, EH Chen, AB Colson, YL Hacker, FH Kozono, D Wee, JO Sher, DJ AF Mak, R. H. Hermann, G. Lewis, J. H. Baldini, E. H. Chen, A. B. Colson, Y. L. Hacker, F. H. Kozono, D. Wee, J. O. Sher, D. J. TI Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With K-ras-Mutant Non-Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Mak, R. H.; Hermann, G.; Lewis, J. H.; Baldini, E. H.; Chen, A. B.; Hacker, F. H.; Kozono, D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mak, R. H.; Lewis, J. H.; Baldini, E. H.; Chen, A. B.; Colson, Y. L.; Hacker, F. H.; Kozono, D.; Wee, J. O.] Harvard Univ, Sch Med, Boston, MA USA. [Colson, Y. L.; Wee, J. O.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sher, D. J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S506 EP S506 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601705 ER PT J AU Mandeville, HC Ladra, MM Padera, TP MacDonald, SM Friedmann, AM Tarbell, N Yock, TI AF Mandeville, H. C. Ladra, M. M. Padera, T. P. MacDonald, S. M. Friedmann, A. M. Tarbell, N. Yock, T. I. TI Local Failure in Parameningeal Rhabdomyosarcoma: Does Response to Induction Chemotherapy Matter? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Mandeville, H. C.] Royal Marsden Hosp, Sutton, Surrey, England. [Ladra, M. M.; Padera, T. P.; MacDonald, S. M.; Friedmann, A. M.; Tarbell, N.; Yock, T. I.] Massachusetts Gen Hosp, Boston, MA 02114 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S70 EP S70 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600170 ER PT J AU Marciscano, AE Stemmer-Rachamimov, AO Niemierko, A Curry, WT Barker, FG Martuza, RL Oh, KS Loeffler, JS Shih, HA AF Marciscano, A. E. Stemmer-Rachamimov, A. O. Niemierko, A. Curry, W. T. Barker, F. G. Martuza, R. L. Oh, K. S. Loeffler, J. S. Shih, H. A. TI Benign Meningiomas With Atypical Features: Correlation of Histopathological Features With Clinical Outcomes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Marciscano, A. E.; Stemmer-Rachamimov, A. O.; Niemierko, A.; Curry, W. T.; Barker, F. G.; Martuza, R. L.; Oh, K. S.; Loeffler, J. S.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S159 EP S159 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600393 ER PT J AU Martin, NE Molodowitch, C Vivenzio, T Czerminska, M Walsh, G Mamon, H Killoran, J AF Martin, N. E. Molodowitch, C. Vivenzio, T. Czerminska, M. Walsh, G. Mamon, H. Killoran, J. TI Development and Implementation of Customized Software for Physician Peer Review and Clinical Care SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Martin, N. E.; Molodowitch, C.; Vivenzio, T.; Czerminska, M.; Walsh, G.; Mamon, H.; Killoran, J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S587 EP S587 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602209 ER PT J AU McBride, SM Kuhlthau, KA Blossom, J Van Der Weerd, E Delahaye, J MacDonald, SM Tarbell, NJ Yock, TI AF McBride, S. M. Kuhlthau, K. A. Blossom, J. Van Der Weerd, E. Delahaye, J. MacDonald, S. M. Tarbell, N. J. Yock, T. I. TI The Impact of Socioeconomic Factors on Health-Related Quality-of-Life (HR-QOL) After Proton Radiation Therapy for a Pediatric CNS Cohort SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [McBride, S. M.; Kuhlthau, K. A.; Van Der Weerd, E.; Delahaye, J.; MacDonald, S. M.; Tarbell, N. J.; Yock, T. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blossom, J.] Harvard Univ, Ctr Geog Anal, Boston, MA 02115 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S593 EP S594 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602224 ER PT J AU Mirabeau-Beale, KL Hong, TS Ancukiewicz, M Ryan, DP Blaszkowsky, LS Drapek, LC Cusack, JCJ Kachnic, LA Wo, JY AF Mirabeau-Beale, K. L. Hong, T. S. Ancukiewicz, M. Ryan, D. P. Blaszkowsky, L. S. Drapek, L. C. Cusack, J. C. J. Kachnic, L. A. Wo, J. Y. TI Clinical and Treatment Factors Associated With Vaginal Stenosis After Definitive Chemoradiation for Anal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Mirabeau-Beale, K. L.] Harvard Radiat Oncol Program, Boston, MA USA. [Hong, T. S.; Ancukiewicz, M.; Ryan, D. P.; Blaszkowsky, L. S.; Drapek, L. C.; Cusack, J. C. J.; Wo, J. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kachnic, L. A.] Boston Univ, Boston Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S74 EP S75 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600181 ER PT J AU Moteabbed, M Yock, TI Paganetti, H AF Moteabbed, M. Yock, T. I. Paganetti, H. TI When Does Pencil Beam Scanning Improve the Treatment Outcome of Pediatric Head-and-Neck/CNS Patients Over Passive Scattered Proton Therapy? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Moteabbed, M.; Yock, T. I.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moteabbed, M.; Yock, T. I.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S184 EP S184 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600455 ER PT J AU Mouw, K Sethi, R Macdonald, SM Tarbell, NJ Yock, TI Munzenrider, JE Grabowski, E Mukai, S Shih, HA AF Mouw, K. Sethi, R. Macdonald, S. M. Tarbell, N. J. Yock, T. I. Munzenrider, J. E. Grabowski, E. Mukai, S. Shih, H. A. TI Proton Radiation Therapy for the Treatment of Pediatric Retinoblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Mouw, K.] Harvard Radiat Oncol Program, Boston, MA USA. [Sethi, R.; Macdonald, S. M.; Tarbell, N. J.; Yock, T. I.; Munzenrider, J. E.; Shih, H. A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grabowski, E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Mukai, S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S37 EP S37 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600088 ER PT J AU Nguyen, PL Je, Y Hoffman, KE Choueiri, TK AF Nguyen, P. L. Je, Y. Hoffman, K. E. Choueiri, T. K. TI Meta-Analysis of Long-term Results of Randomized Trials of the Impact of Adjuvant Radiation on Overall, Metastasis-Free, and Biochemical Recurrence-Free Survival for pT3N0 or Margin-Positive Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Nguyen, P. L.; Je, Y.; Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoffman, K. E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S107 EP S107 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600262 ER PT J AU Ngwa, W Korideck, H Kumar, R Sridhar, S David, K Paul, N Berbeco, R Cormack, R Makrigiorgos, G AF Ngwa, W. Korideck, H. Kumar, R. Sridhar, S. David, K. Paul, N. Berbeco, R. Cormack, R. Makrigiorgos, G. TI Toward Customizable Radiation Therapy Enhancement (CuRE) With Gold Nanoparticles Released, In Situ, From Gold-Loaded Brachytherapy Spacers SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Ngwa, W.; David, K.; Paul, N.; Berbeco, R.; Cormack, R.; Makrigiorgos, G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Korideck, H.; Kumar, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kumar, R.; Sridhar, S.] Northeastern Univ, Boston, MA 02115 USA. [Sridhar, S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S151 EP S151 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600373 ER PT J AU Pan, E Goldberg, SI Chen, YL Giraud, C Hornick, JL Nielsen, GP Hornicek, FJ Raut, CP DeLaney, TF Baldini, EH AF Pan, E. Goldberg, S. I. Chen, Y. L. Giraud, C. Hornick, J. L. Nielsen, G. P. Hornicek, F. J. Raut, C. P. DeLaney, T. F. Baldini, E. H. TI Role of Postoperative Radiation (RT) Boost for Soft Tissue Sarcomas With Positive Margins Following Preoperative RT and Resection SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Pan, E.; Goldberg, S. I.; Chen, Y. L.; Giraud, C.; Nielsen, G. P.; Hornicek, F. J.; DeLaney, T. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hornick, J. L.; Raut, C. P.; Baldini, E. H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hornick, J. L.; Raut, C. P.; Baldini, E. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S65 EP S65 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600157 ER PT J AU Parikh, RB Cronin, A Kozono, DE Oxnard, GR Mak, RH Jackman, DM Lo, PC Baldini, EH Johnson, BE Chen, AB AF Parikh, R. B. Cronin, A. Kozono, D. E. Oxnard, G. R. Mak, R. H. Jackman, D. M. Lo, P. C. Baldini, E. H. Johnson, B. E. Chen, A. B. TI Factors Associated With Survival in Patients With Oligometastatic Non-Small Cell Lung Cancer (NSCLC) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Parikh, R. B.] Harvard Univ, Sch Med, Boston, MA USA. [Cronin, A.; Oxnard, G. R.; Jackman, D. M.; Lo, P. C.; Johnson, B. E.; Chen, A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kozono, D. E.; Baldini, E. H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mak, R. H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S202 EP S202 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600501 ER PT J AU Patel, SA Rochet, N Jimenez, RB Lu, H Nyamwanda, JA Hickey, SB Napolitano, BN Taghian, AG MacDonald, SM AF Patel, S. A. Rochet, N. Jimenez, R. B. Lu, H. Nyamwanda, J. A. Hickey, S. B. Napolitano, B. N. Taghian, A. G. MacDonald, S. M. TI Protons With Free Breathing Versus Photons With Deep Inspiration Breath-Hold in Postmastectomy Patients: A Dosimetric Comparative Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Patel, S. A.; Rochet, N.; Jimenez, R. B.; Lu, H.; Nyamwanda, J. A.; Hickey, S. B.; Napolitano, B. N.; Taghian, A. G.; MacDonald, S. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S47 EP S47 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600113 ER PT J AU Quang, TS AF Quang, T. S. TI Privilege and Immunity - An Underutilized Tool in the Quality Improvement Program SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Quang, T. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Quang, T. S.] Univ Washington, Med Ctr, Seattle, WA 98195 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S578 EP S578 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602185 ER PT J AU Rajakesari, S Arvold, ND Christianson, LW Jimenez, RB Friesen, S Mannarino, E Wagar, M Hacker, FL Weiss, SE Alexander, BM AF Rajakesari, S. Arvold, N. D. Christianson, L. W. Jimenez, R. B. Friesen, S. Mannarino, E. Wagar, M. Hacker, F. L. Weiss, S. E. Alexander, B. M. TI Hypofractionated Stereotactic Radiation Therapy for Brain Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Rajakesari, S.; Arvold, N. D.; Christianson, L. W.; Jimenez, R. B.; Friesen, S.; Mannarino, E.; Wagar, M.; Hacker, F. L.; Alexander, B. M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Weiss, S. E.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S276 EP S276 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601106 ER PT J AU Recht, A Li, J Wang, H Pelletier, S Avigan, D Freedman, R Huberman, M Mamon, H Ng, A Shields, H AF Recht, A. Li, J. Wang, H. Pelletier, S. Avigan, D. Freedman, R. Huberman, M. Mamon, H. Ng, A. Shields, H. TI Esophageal Symptoms Before, During, and 1 Year After Treatment and Sequencing of Chemotherapy (CT) and Mediastinal Radiation Therapy (MRT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Recht, A.; Li, J.; Wang, H.; Avigan, D.; Huberman, M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pelletier, S.] Harvard Univ, Sch Med, Boston, MA USA. [Freedman, R.; Mamon, H.; Ng, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mamon, H.; Ng, A.; Shields, H.] 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S117 EP S117 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600288 ER PT J AU Roach, M Hunt, D Lawton, CA Hsu, I Lustig, RA Seider, M Christopher, JU Thomas, CR Shipley, WU Sandler, H AF Roach, M. Hunt, D. Lawton, C. A. Hsu, I. Lustig, R. A. Seider, M. Christopher, J. U. Thomas, C. R. Shipley, W. U. Sandler, H. TI Radiation Therapy Oncology Group (RTOG) 9413: A Randomized Trial Comparing Whole pelvic Radiation Therapy (WPRT) to Prostate Only (PORT) and Neoadjuvant Hormonal Therapy (NHT) to Adjuvant Hormonal Therapy (AHT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Roach, M.; Hsu, I.] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Hunt, D.] RTOG Stat, Philadelphia, PA USA. [Lawton, C. A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Lustig, R. A.] Perelman Ctr Adv Med, Dept Radiat Oncol, Philadelphia, PA USA. [Seider, M.] Akron City Hosp, Akron, OH USA. [Christopher, J. U.] Radiol Assoc Sacramento, Sacramento, CA USA. [Thomas, C. R.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Shipley, W. U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sandler, H.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr, Los Angeles, CA 90048 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S106 EP S107 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600261 ER PT J AU Rochet, N Batin, E Depauw, N Jee, K Kooy, HM Khan, FH Paetzold, PJ Russell, AH Bortfeld, TR Craft, DL AF Rochet, N. Batin, E. Depauw, N. Jee, K. Kooy, H. M. Khan, F. H. Paetzold, P. J. Russell, A. H. Bortfeld, T. R. Craft, D. L. TI Advances in Whole Abdominal Irradiation: What Protons, VMAT, and IMRT Using Multicriteria Optimization Can Offer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Rochet, N.; Batin, E.; Depauw, N.; Jee, K.; Kooy, H. M.; Khan, F. H.; Paetzold, P. J.; Russell, A. H.; Bortfeld, T. R.; Craft, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Rochet, N.] Heidelberg Univ, Dept Radiat Oncol, Heidelberg, Germany. [Depauw, N.] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S748 EP S749 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602622 ER PT J AU Rochet, N Drake, JI Harrington, K Wolfgang, JA Napolitano, B Sadek, BT Shenouda, MN Keruakous, AR Niemierko, A Taghian, A AF Rochet, N. Drake, J. I. Harrington, K. Wolfgang, J. A. Napolitano, B. Sadek, B. T. Shenouda, M. N. Keruakous, A. R. Niemierko, A. Taghian, A. TI Deep Inspiration Breath-Hold Technique in Left-Sided Breast Cancer Radiation Therapy: Evaluating Cardiac Contact Distance as a Predictor of Cardiac Exposure SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Rochet, N.; Drake, J. I.; Harrington, K.; Wolfgang, J. A.; Napolitano, B.; Sadek, B. T.; Shenouda, M. N.; Keruakous, A. R.; Niemierko, A.; Taghian, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Rochet, N.] Heidelberg Univ, Dept Radiat Oncol, Heidelberg, Germany. RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S197 EP S198 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600490 ER PT J AU Russo, AL Truong, M Busse, PM Adams, J Deschler, DG Lin, DT Wirth, L John, CR Chan, AW AF Russo, A. L. Truong, M. Busse, P. M. Adams, J. Deschler, D. G. Lin, D. T. Wirth, L. John, C. R. Chan, A. W. TI Long-term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Russo, A. L.] Harvard Radiat Oncol Program, Boston, MA USA. [Truong, M.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Busse, P. M.; Adams, J.; Chan, A. W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Deschler, D. G.; Lin, D. T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wirth, L.; John, C. R.] Massachusetts Gen Hosp, Dept Med Oncol, 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S457 EP S458 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601580 ER PT J AU Russo, AL Kwak, EL Borger, DR Szymonifka, J Mullen, JT Zhu, AX Blaszkowsky, LS Wo, JY Ryan, DP Hong, TS AF Russo, A. L. Kwak, E. L. Borger, D. R. Szymonifka, J. Mullen, J. T. Zhu, A. X. Blaszkowsky, L. S. Wo, J. Y. Ryan, D. P. Hong, T. S. TI Mutational Profile of Gastroesophageal Cancer Compared to Gastric and Esophageal Cancers SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Russo, A. L.] Harvard Radiat Oncol Program, Boston, MA USA. [Kwak, E. L.; Borger, D. R.; Zhu, A. X.; Blaszkowsky, L. S.; Ryan, D. P.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Szymonifka, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mullen, J. T.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [Wo, J. Y.; Hong, T. S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S85 EP S85 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600208 ER PT J AU Russo, AL Niemierko, A Wong, NL Arvold, N Wong, J Bellon, JR Punglia, RS Brock, JE Harris, JR AF Russo, A. L. Niemierko, A. Wong, N. L. Arvold, N. Wong, J. Bellon, J. R. Punglia, R. S. Brock, J. E. Harris, J. R. TI Margin Status and the Risk of Local Recurrence (LR) in Patients With Early-Stage Breast Cancer Treated With Breast-Conserving Therapy (BCT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Russo, A. L.] Harvard Radiat Oncol Program, Boston, MA USA. [Niemierko, A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Wong, N. L.; Arvold, N.; Wong, J.; Bellon, J. R.; Punglia, R. S.; Harris, J. R.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Brock, J. E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S8 EP S9 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600020 ER PT J AU Sadek, BT Homayounfar, G Raad, RFA Shenouda, MN Keruakous, AR Niemierko, A Taghian, AG AF Sadek, B. T. Homayounfar, G. Raad, R. F. Abi Shenouda, M. N. Keruakous, A. R. Niemierko, A. Taghian, A. G. TI Higher Boost Dose of Radiation Instead of Mastectomy for Patients With Final Positive/Close Margins After Breast-Conserving Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Sadek, B. T.; Homayounfar, G.; Raad, R. F. Abi; Shenouda, M. N.; Keruakous, A. R.; Niemierko, A.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S9 EP S9 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600021 ER PT J AU Sethi, R Yeap, BY Marino, R Marcus, KJ Caruso, P Pulsifer, KB Ebb, D Tarbell, NJ Yock, TI MacDonald, SM AF Sethi, R. Yeap, B. Y. Marino, R. Marcus, K. J. Caruso, P. Pulsifer, K. B. Ebb, D. Tarbell, N. J. Yock, T. I. MacDonald, S. M. TI Proton Radiation Therapy for Pediatric Central Nervous System Ependymoma: Clinical Outcomes for 70 patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Sethi, R.] Harvard Univ, Sch Med, Boston, MA USA. [Yeap, B. Y.; Marino, R.; Caruso, P.; Pulsifer, K. B.; Ebb, D.; Tarbell, N. J.; Yock, T. I.; MacDonald, S. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marcus, K. J.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S275 EP S276 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601105 ER PT J AU Shenouda, MN Sadek, BT Keruakous, AR Goldberg, S Raad, RFA Taghian, AG AF Shenouda, M. N. Sadek, B. T. Keruakous, A. R. Goldberg, S. Raad, R. F. Abi Taghian, A. G. TI Clinical Outcome of Isolate Local-Regional Recurrence in Breast Cancer Patients According to Their Primary Local Treatment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Shenouda, M. N.; Sadek, B. T.; Keruakous, A. R.; Goldberg, S.; Raad, R. F. Abi; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S227 EP S228 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600567 ER PT J AU Shih, HA Niu, NN Pan, E Daartz, J Yeap, BY Munzenrider, JE Loeffler, JS AF Shih, H. A. Niu, N. N. Pan, E. Daartz, J. Yeap, B. Y. Munzenrider, J. E. Loeffler, J. S. TI Mixed Proton and Photon Therapy for Benign Meningiomas: Long-term Results of a Prospective Randomized Dose Escalation Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Shih, H. A.; Niu, N. N.; Pan, E.; Daartz, J.; Yeap, B. Y.; Munzenrider, J. E.; Loeffler, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S158 EP S159 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600392 ER PT J AU Terezakis, SA MacDonald, S Dieckmann, K Nilsson, K Villar, R Nechesnyuk, A Winey, B Ford, E Malet, C Tryggestad, E AF Terezakis, S. A. MacDonald, S. Dieckmann, K. Nilsson, K. Villar, R. Nechesnyuk, A. Winey, B. Ford, E. Malet, C. Tryggestad, E. TI Clinical Practice Patterns of Pediatric Image Guided Radiation Treatment: Results From an International Pediatric Research Consortium SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Terezakis, S. A.] Johns Hopkins Sch Med, Baltimore, MD USA. [MacDonald, S.; Winey, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dieckmann, K.] Univ Klin Strahlentherapie & Strahlenbiol, Vienna, Austria. [Nilsson, K.] Uppsala Univ, Akad Sjukhuset, Uppsala, Sweden. [Villar, R.] Boldrini Hosp, Sao Paulo, Brazil. [Nechesnyuk, A.] Fed Sci Clin Ctr Childrens Hematol Oncol & Immuno, Moscow, Russia. [Ford, E.] Univ Washington, Seattle, WA 98195 USA. [Malet, C.] Ctr Lutte Contre Canc Leon Berard, Lyon, France. [Tryggestad, E.] Mayo Clin, Rochester, MN 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S602 EP S603 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503602245 ER PT J AU Tseng, YD Krishnan, M Sullivan, AJ Jones, J Balboni, TA AF Tseng, Y. D. Krishnan, M. Sullivan, A. J. Jones, J. Balboni, T. A. TI How Radiation Oncologists Evaluate and Incorporate Life Expectancy Estimates Into the Palliative Treatment of Cancer Patients: A Survey-Based Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Tseng, Y. D.; Krishnan, M.] Harvard Radiat Oncol Program, Boston, MA USA. [Sullivan, A. J.] Harvard Univ, Dept Biostat, Cambridge, MA 02138 USA. [Jones, J.] Harvard Palliat Med Fellowship Program, Boston, MA USA. [Balboni, T. A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Balboni, T. A.] 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S90 EP S90 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600220 ER PT J AU Tseng, YD Chen, Y Catalano, P Mauch, PM Ng, A AF Tseng, Y. D. Chen, Y. Catalano, P. Mauch, P. M. Ng, A. TI Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Tseng, Y. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Y.; Catalano, P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mauch, P. M.; Ng, A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S60 EP S60 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600145 ER PT J AU Vega, RM Kim, J Bussiere, M Hattangadi, J Hollander, A Michalski, J Tarbell, N Yock, T MacDonald, S AF Vega, R. Mailhot Kim, J. Bussiere, M. Hattangadi, J. Hollander, A. Michalski, J. Tarbell, N. Yock, T. MacDonald, S. TI Cost-Effectiveness of Proton Therapy Compared to Photon Therapy in the Management of Pediatric Medulloblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Vega, R. Mailhot] Washington Univ, Sch Med, St Louis, MO USA. [Kim, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bussiere, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hattangadi, J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Hollander, A.] Washington Univ, St Louis Childrens Hosp, Sch Med, St Louis, MO 63110 USA. [Michalski, J.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Tarbell, N.; Yock, T.; MacDonald, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S5 EP S5 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600011 ER PT J AU Viswanathan, AN Erickson, B Beriwal, S D'Souza, DP Jones, EL Portelance, L Small, W Yashar, CM Gaffney, DK Bosch, W AF Viswanathan, A. N. Erickson, B. Beriwal, S. D'Souza, D. P. Jones, E. L. Portelance, L. Small, W. Yashar, C. M. Gaffney, D. K. Bosch, W. TI Consensus Contours for CT Versus MRI in Image-Based Brachytherapy for Cervix Cancer to Generate an RTOG Atlas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Viswanathan, A. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Erickson, B.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Beriwal, S.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [D'Souza, D. P.] London Hlth Sci Ctr, London, ON, Canada. [D'Souza, D. P.] Univ Western Ontario, London, ON, Canada. [Jones, E. L.] Univ N Carolina, Chapel Hill, NC USA. [Portelance, L.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Small, W.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Yashar, C. M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Gaffney, D. K.] Univ Utah, Huntsman Canc Hosp, Salt Lake City, UT USA. [Bosch, W.] Washington Univ, St Louis, MO USA. RI Beriwal, Sushil/J-6404-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S30 EP S30 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600072 ER PT J AU Viswanathan, AN Moughan, J Miller, BE Xiao, Y Matulonis, UA Horowitz, NS Mannel, RS Souhami, L Erickson, B Gaffney, DK AF Viswanathan, A. N. Moughan, J. Miller, B. E. Xiao, Y. Matulonis, U. A. Horowitz, N. S. Mannel, R. S. Souhami, L. Erickson, B. Gaffney, D. K. TI A Phase 2 Study of Postoperative Intensity Modulated Radiation Therapy (IMRT) With Concurrent Cisplatin and Bevacizumab (Bev) Followed by Carboplatin and Paclitaxel for Patients With Endometrial Cancer: One-Year Results from RTOG 0921 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Viswanathan, A. N.; Matulonis, U. A.; Horowitz, N. S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Moughan, J.] RTOG Stat Ctr, Philadelphia, PA USA. [Miller, B. E.] Northeast Oncol Associates, High Point, NC USA. [Xiao, Y.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Mannel, R. S.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Souhami, L.] McGill Univ, Montreal, PQ, Canada. [Erickson, B.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gaffney, D. K.] Univ Utah, Huntsman Canc Hosp, Salt Lake City, UT USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S4 EP S5 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600010 ER PT J AU Warren, L Miller, CL Horick, N Skolny, MN Jammallo, LS Sadek, BT Shenouda, MN O'Toole, J Specht, MC Taghian, AG AF Warren, L. Miller, C. L. Horick, N. Skolny, M. N. Jammallo, L. S. Sadek, B. T. Shenouda, M. N. O'Toole, J. Specht, M. C. Taghian, A. G. TI Risk of Lymphedema With the Addition of Regional Lymph Node Irradiation for Breast Cancer Therapy: A Prospective Cohort Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Warren, L.] Harvard Radiat Oncol Program, Boston, MA USA. [Miller, C. L.; Horick, N.; Skolny, M. N.; Jammallo, L. S.; Sadek, B. T.; Shenouda, M. N.; O'Toole, J.; Specht, M. C.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S47 EP S48 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600114 ER PT J AU Wattson, DA Tanguturi, SK Spiegel, DY Niemierko, A Biller, BMK Nachtigall, LB Swearingen, B Chapman, PH Loeffler, JS Shih, HA AF Wattson, D. A. Tanguturi, S. K. Spiegel, D. Y. Niemierko, A. Biller, B. M. K. Nachtigall, L. B. Swearingen, B. Chapman, P. H. Loeffler, J. S. Shih, H. A. TI Outcomes of Proton Radiation Therapy for Patients With Functional Pituitary Adenomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Wattson, D. A.; Tanguturi, S. K.] Harvard Radiat Oncol Program, Boston, MA USA. [Spiegel, D. Y.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Niemierko, A.; Loeffler, J. S.; Shih, H. A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Biller, B. M. K.; Nachtigall, L. B.] Massachusetts Gen Hosp, Neuroendicrine Unit, Boston, MA 02114 USA. [Swearingen, B.; Chapman, P. H.] Massachusetts Gen Hosp, Dept Neurosurg, 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S264 EP S264 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601075 ER PT J AU Wattson, DA DiPiro, PJ Das, P Hodgson, DC Mauch, PM Ng, AK AF Wattson, D. A. DiPiro, P. J. Das, P. Hodgson, D. C. Mauch, P. M. Ng, A. K. TI Low-Dose Chest CT for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Wattson, D. A.] Harvard Radiat Oncol Program, Boston, MA USA. [DiPiro, P. J.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Das, P.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Hodgson, D. C.] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Mauch, P. M.; Ng, A. K.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Mauch, P. M.; Ng, A. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S180 EP S180 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600447 ER PT J AU Willers, H Wang, M Liu, Q Kern, A Hong, TS Held, KD Benes, C Efstathiou, J AF Willers, H. Wang, M. Liu, Q. Kern, A. Hong, T. S. Held, K. D. Benes, C. Efstathiou, J. TI Identification of Radiosensitizing Targeted Drugs and Associated Genomic Biomarkers by a Cell Line Screening Platform SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Willers, H.; Wang, M.; Liu, Q.; Kern, A.; Hong, T. S.; Held, K. D.; Benes, C.; Efstathiou, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S138 EP S138 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503600340 ER PT J AU Wo, JY Fernandez-del Castillo, C Lillemoe, KD Ferrone, CR Ryan, DP Blaszkowsky, LS Szymonifka, J Hong, TS AF Wo, J. Y. Fernandez-del Castillo, C. Lillemoe, K. D. Ferrone, C. R. Ryan, D. P. Blaszkowsky, L. S. Szymonifka, J. Hong, T. S. TI Tolerability of Dose Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally-Advanced Pancreatic Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Wo, J. Y.; Fernandez-del Castillo, C.; Lillemoe, K. D.; Ferrone, C. R.; Ryan, D. P.; Blaszkowsky, L. S.; Szymonifka, J.; Hong, T. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S311 EP S312 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601202 ER PT J AU Wu, AJ Goodman, KA Chang, DT Hong, TS Jabbour, SK Kleinberg, LR Mamon, HJ Thomas, CR Bosch, WR AF Wu, A. J. Goodman, K. A. Chang, D. T. Hong, T. S. Jabbour, S. K. Kleinberg, L. R. Mamon, H. J. Thomas, C. R. Bosch, W. R. TI Generation of Consensus Contour Atlas for Esophageal Cancer IMRT SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY SEP 22-25, 2013 CL Atlanta, GA SP Amer Soc Radiat Oncol C1 [Wu, A. J.; Goodman, K. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chang, D. T.] Stanford Univ, Palo Alto, CA 94304 USA. [Hong, T. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jabbour, S. K.] Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA. [Kleinberg, L. R.] Johns Hopkins Univ, Baltimore, MD USA. [Mamon, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thomas, C. R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bosch, W. R.] Washington Univ, St Louis, MO 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 SU S BP S293 EP S293 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 219JY UT WOS:000324503601152 ER PT J AU Walton, E Turner, JA Ehrlich, S AF Walton, Esther Turner, Jessica A. Ehrlich, Stefan TI Neuroimaging as a potential biomarker to optimize psychiatric research and treatment SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; NAIVE 1ST-EPISODE SCHIZOPHRENIA; DORSOLATERAL PREFRONTAL CORTEX; MONOZYGOTIC TWINS DISCORDANT; FACTOR VAL66MET POLYMORPHISM; PREDICTS TREATMENT RESPONSE; 1ST EPISODE PSYCHOSIS; FACTOR-H POLYMORPHISM; MB-COMT PROMOTER; WORKING-MEMORY AB Complex, polygenic phenotypes in psychiatry hamper our understanding of the underlying molecular pathways and mechanisms of many diseases. The unknown aetiology, together with symptoms which often show a large variability both across individuals and over time and also tend to respond comparatively slowly to medication, can be a problem for patient treatment and drug development. We argue that neuroimaging has the potential to improve psychiatric treatment in two ways. First, by reducing phenotypic complexity, neuroimaging intermediate phenotypes can help to identify disease-related genes and can shed light into the biological mechanisms of known risk genes. Second, quantitative neuroimaging markers-reflecting the spectrum of impairment on a brain-based level-can be used as a more sensitive, reliable and immediate treatment response biomarker. In the end, enhancing both our understanding of the pathophysiology of psychiatric disorders and the prediction of treatment success could eventually optimise current therapy plans. C1 [Walton, Esther; Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, D-01307 Dresden, Germany. [Turner, Jessica A.] Mind Res Network, Albuquerque, NM USA. [Turner, Jessica A.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Ehrlich, Stefan] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, MGH MIT HMS, Charlestown, MA USA. RP Walton, E (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, Fetscherstr 74, D-01307 Dresden, Germany. EM esther.walton@uniklinikum-dresden.de RI Turner, Jessica/H-7282-2015; OI Turner, Jessica/0000-0003-0076-8434; Ehrlich, Stefan/0000-0003-2132-4445; Walton, Esther/0000-0002-0935-2200 FU NIMH NIH HHS [1R01MH094524] NR 139 TC 1 Z9 1 U1 5 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0954-0261 EI 1369-1627 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD OCT PY 2013 VL 25 IS 5 BP 619 EP 631 DI 10.3109/09540261.2013.816659 PG 13 WC Psychiatry SC Psychiatry GA 240SW UT WOS:000326118300010 PM 24151806 ER PT J AU Duivenvoorden, R Mani, V Woodward, M Kallend, D Suchankova, G Fuster, V Rudd, JHF Tawakol, A Farkouh, ME Fayad, ZA AF Duivenvoorden, Raphael Mani, Venkatesh Woodward, Mark Kallend, David Suchankova, Gabriela Fuster, Valentin Rudd, James H. F. Tawakol, Ahmed Farkouh, Michael E. Fayad, Zahi A. TI Relationship of Serum Inflammatory Biomarkers With Plaque Inflammation Assessed by FDG PET/CT The dal-PLAQUE Study SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; fluorodeoxyglucose F 18 positron emission tomography; inflammatory biomarkers ID CORONARY-HEART-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; MYELOPEROXIDASE LEVELS; ARTERIAL INFLAMMATION; RISK-FACTORS; ATHEROSCLEROSIS; PREDICTION AB OBJECTIVES This study sought to longitudinally investigate the relationship between a broad spectrum of serum inflammatory biomarkers and plaque inflammation assessed by F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). BACKGROUND Both plaque inflammation and serum biomarkers of inflammation are associated with atherothrombotic events; however, the relationship between them is unclear. METHODS We conducted a post hoc analysis of the dal-PLAQUE (A Randomized Placebo-Controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Hague in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors), a randomized, placebo-controlled study of dalcetrapib, a cholesteryl ester transfer protein inhibitor, in 130 patients with coronary heart disease, or coronary heart disease risk equivalents on stable lipid-lowering therapy. Baseline and change after 3-month follow-up in inflammatory biomarker levels and baseline and change after 3-month follow-up in aorta and carotid F-18-FDG PET/CT (mean maximum target-to-background ratio of the most diseased segment [TBRmds]) were analyzed. RESULTS Baseline myeloperoxidase positively correlated with baseline carotid TBRmds (rho = 0.25, p = 0.02). This correlation remained at the 3-month follow-up and was independent of traditional cardiovascular disease risk factors. Baseline lipoprotein-associated phospholipase A(2) mass correlated with aorta TBRmds (rho = 0.21, p = 0.03). However, this correlation disappeared at the 3-month follow-up and was not independent of cardiovascular disease risk factors. There was no association between change from baseline in myeloperoxidase or lipoprotein-associated phospholipase A(2) mass and change from baseline in aorta and carotid TBRmds. Baseline and change from baseline in high sensitivity C-reactive protein, interleukin 6, soluble P-selectin, soluble E-selectin, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and matrix-metalloproteinase 3 and 9 did not correlate with baseline or change from baseline in carotid or aorta TBRmds. CONCLUSIONS Our data show that, in patients with coronary heart disease or at high risk of coronary heart disease on stable lipid-lowering therapy, circulating myeloperoxidase levels are associated with carotid plaque inflammation. (A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors [dal-PLAQUE]; NCT00655473) (C) 2013 by the American College of Cardiology Foundation C1 [Duivenvoorden, Raphael; Mani, Venkatesh; Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Woodward, Mark] Univ Sydney, George Inst, Sydney, NSW 2006, Australia. [Kallend, David; Suchankova, Gabriela] F Hoffmann La Roche Ltd, Basel, Switzerland. [Fuster, Valentin; Farkouh, Michael E.; Fayad, Zahi A.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY 10029 USA. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Farkouh, Michael E.] Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Farkouh, Michael E.] Li Ka Shing Knowledge Inst, Toronto, ON, Canada. RP Fayad, ZA (reprint author), Mt Sinai Sch Med, Translat & Mol Imaging Inst, 1 Gustave L Levy Pl,POB 1234, New York, NY 10029 USA. EM zahi.fayad@mssm.edu RI Mani, Venkatesh/B-8939-2011; Woodward, Mark/D-8492-2015; Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Rudd, James/0000-0003-2243-3117; Mani, Venkatesh/0000-0002-0432-2918 FU F. Hoffmann-La Roche Ltd.; Tursiop Inc.; National Institute for Health Research Cambridge Biomedical Research Centre; Merck; Bristol-Myers Squibb; Genentech; GlaxoSmithKline; VBL Therapeutics; Roche; Novartis; Via Pharmaceuticals FX The dal-PLAQUE study was funded by F. Hoffmann-La Roche Ltd., who also provided third-party editorial support, through Prime Healthcare, for the preparation of the manuscript. Dr. Mani has received consulting fees from Tursiop Inc. Dr. Woodward has received honoraria from F. Hoffmann-La Roche Ltd.; and has served on the steering committee of dal-PLAQUE. Dr. Kallend is a salaried employee with stock options of The Medicines Company. Dr. Suchankova is an employee of F. Hoffmann-La Roche Ltd. Dr. Rudd has received honoraria from F. Hoffmann-La Roche Ltd.; and his work has been supported in part by the National Institute for Health Research Cambridge Biomedical Research Centre. Dr. Tawakol has received honoraria from F. Hoffmann-La Roche Ltd., Bristol-Myers Squibb, and Novartis; research grants from Merck, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, and VBL Therapeutics; and consulting fees and grants from Roche. Dr. Farkouh has received honoraria from F. Hoffmann-La Roche Ltd.; and has received consulting fees from Genentech. Dr. Fayad has reported that he has received research grants from F. Hoffmann-La Roche Ltd., GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb, and Via Pharmaceuticals; and has received honoraria from F. Hoffmann-La Roche Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 30 TC 14 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD OCT PY 2013 VL 6 IS 10 BP 1087 EP 1094 DI 10.1016/j.jcmg.2013.03.009 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 241YT UT WOS:000326205300008 PM 24135322 ER PT J AU Punglia, RS Schnitt, SJ Weeks, JC AF Punglia, Rinaa S. Schnitt, Stuart J. Weeks, Jane C. TI Treatment of Ductal Carcinoma In Situ After Excision: Would a Prophylactic Paradigm Be More Appropriate? SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SURGICAL ADJUVANT BREAST; RANDOMIZED CONTROLLED-TRIAL; LOCAL RECURRENCE; CONSERVING TREATMENT; MYOEPITHELIAL CELLS; CANCER; WOMEN; RISK; TAMOXIFEN; RADIOTHERAPY AB Corresponding to the increased use of mammography, the incidence of ductal carcinoma in situ (DCIS) has risen dramatically in the past 30 years. Despite its growing incidence, the treatment of DCIS remains highly variable and controversial. Although DCIS itself does not metastasize and is never lethal, it may be a precursor of invasive breast cancer and is a marker of increased breast cancer risk. Confusing a precursor lesion with cancer, many clinicians apply an invasive breast cancer treatment paradigm to DCIS patients, offering adjuvant radiation therapy and tamoxifen after diagnosis. In this commentary, we outline the issues associated with DCIS managementuis DCIS a cancer, a precursor of cancer, or a marker of invasive carcinoma risk? Specifically, we argue that consideration be given to removing the term carcinoma from DCIS, using cancer occurrence to mean the diagnosis of invasive cancer after DCIS instead of recurrence, and make the argument that a prophylactic paradigm of treatment after excision may be more appropriate. C1 [Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02215 USA. [Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1114A, Boston, MA 02215 USA. EM rpunglia@partners.org NR 44 TC 20 Z9 20 U1 0 U2 0 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-. Natl. Cancer Inst. PD OCT PY 2013 VL 105 IS 20 BP 1527 EP 1533 DI 10.1093/jnci/djt256 PG 7 WC Oncology SC Oncology GA 239RS UT WOS:000326043700006 PM 24068769 ER PT J AU Cassol, E Malfeld, S Mahasha, P Bond, R Slavik, T Seebregts, C Poli, G Cassol, S van der Merwe, SW Rossouw, T AF Cassol, Edana Malfeld, Susan Mahasha, Phetole Bond, Robert Slavik, Tomas Seebregts, Chris Poli, Guido Cassol, Sharon van der Merwe, Schalk W. Rossouw, Theresa TI Impaired CD4(+) T-Cell Restoration in the Small Versus Large Intestine of HIV-1-Positive South Africans Receiving Combination Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV-1; antiretroviral therapy; CD4 reconstitution; intestine; Africa; immune activation ID IMMUNODEFICIENCY-VIRUS TYPE-1; MUCOSAL IMMUNE RECONSTITUTION; LYMPHATIC TISSUE FIBROSIS; HIV-INFECTED INDIVIDUALS; LYMPHOID-TISSUE; GASTROINTESTINAL-TRACT; COLLAGEN DEPOSITION; VIRAL SUPPRESSION; DENDRITIC CELLS; GUT AB Background. Human immunodeficiency virus type 1 (HIV-1) infection is associated with a massive depletion of intestinal CD4(+) T cells that is only partially reversed by combination antiretroviral therapy (cART). Here, we assessed the ability of nucleoside reverse-transcriptase inhibitor/nonnucleoside reverse-transcriptase inhibitor treatment to restore the CD4(+) T-cell populations in the intestine of South African patients with AIDS. Methods. Thirty-eight patients with advanced HIV-1 infection who had chronic diarrhea (duration, >4 weeks) and/or unintentional weight loss (>10% decrease from baseline) of uncertain etiology were enrolled. Blood specimens were collected monthly, and gastrointestinal tract biopsy specimens were collected before cART initiation (from the duodenum, jejunum, ileum, and colon), 3 months after cART initiation (from the duodenum), and 6 months after cART initiation (from the duodenum and colon). CD4(+), CD8(+), and CD38(+)CD8(+) T cells were quantified by flow cytometry and immunohistochemistry analyses, and the HIV-1 RNA load was determined by the Nuclisens assay. Results. CD4(+) T-cell and HIV-1 RNA levels were significantly lower, whereas CD8(+) T-cell levels, including activated CD38(+)CD8(+) T cell levels, were higher in the duodenum and jejunum, compared with the colon. After 6 months of cART, a significant but incomplete recovery of CD4(+) T cells was detected in the colon and peripheral blood but not in the duodenum. Failed restoration of the CD4(+) T-cell count in the duodenum was associated with nonspecific enteritis and CD8(+) T-cell activation. Conclusions. Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4(+) T-cell recovery and improve therapeutic outcomes. C1 [Cassol, Edana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Cassol, Edana] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Cassol, Edana; Malfeld, Susan; Mahasha, Phetole; Cassol, Sharon; van der Merwe, Schalk W.] Univ Pretoria, Dept Immunol, Med Res Council Unit Inflammat & Immun, ZA-0002 Pretoria, South Africa. [Bond, Robert; van der Merwe, Schalk W.] Univ Pretoria, Hepatol & Gastrointestinal Res Lab, ZA-0002 Pretoria, South Africa. [Slavik, Tomas] Univ Pretoria, Ampath Pathol Labs, Dept Anat Pathol, ZA-0002 Pretoria, South Africa. [Rossouw, Theresa] Univ Pretoria, Dept Family Med, ZA-0002 Pretoria, South Africa. [Malfeld, Susan; Mahasha, Phetole; Cassol, Sharon; van der Merwe, Schalk W.] Natl Hlth Lab Serv, Tshwane Acad Div, Johannesburg, South Africa. [Seebregts, Chris] MRC, Tygerberg, South Africa. [Poli, Guido] Ist Sci San Raffaele, AIDS Immunopathogenesis Unit, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy. [Poli, Guido] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy. RP Cassol, E (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave,CLS1017, Boston, MA 02215 USA. EM edana_cassol@dfci.harvard.edu FU Delegation of the European Union to South Africa [2007/147-790]; National Research Council of South Africa [61509] FX This work was supported by the Delegation of the European Union to South Africa (grant Sante 2007/147-790, Drug Resistance Surveillence and Treatment Monitoring Network for Public Sector HIV Antiretroviral Treatment Programme in the Free State); the National Research Council of South Africa (Unlocking the Future grant 61509). NR 48 TC 9 Z9 9 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2013 VL 208 IS 7 BP 1113 EP 1122 DI 10.1093/infdis/jit249 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 239ST UT WOS:000326046400010 PM 23749968 ER PT J AU O'Leary, KD Foran, H Cohen, S AF O'Leary, K. Daniel Foran, Heather Cohen, Shiri TI VALIDATION OF FEAR OF PARTNER SCALE SO JOURNAL OF MARITAL AND FAMILY THERAPY LA English DT Article ID INTIMATE PARTNER; GENDER-DIFFERENCES; SPOUSE ABUSE; VIOLENCE; WOMEN; AGGRESSION; CONFLICT; MARRIAGE; RISK; ADJUSTMENT AB Therapists have a responsibility to ascertain if psychological aggression, physical aggression, sexual aggression exist, and if there is fear of the partner. A fear of partner measure was evaluated in 100 couples who sought relationship feedback. Fear of partner's psychological, physical, and sexual aggression was related to actual reports of such behavior. For both men and women, fear of speaking in front of partner and fear of being in therapy with partner were related to reports of psychological aggression perpetrated by the partner, dominance, and isolation by the partner, and one's own marital dissatisfaction. Among respondents who were aggressed against, more men than women reported fear of participating in therapy with their partner. The measure herein can be used to determine the extent of fear of aggression by partners and to assist in the decision-making about the appropriateness of marital therapy and divorce mediation. C1 [O'Leary, K. Daniel] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Foran, Heather] Tech Univ Carolo Wilhelmina Braunschweig, Inst Psychol, Abt Klin Psychol Psychotherapie & Diagnost Humbol, Braunschweig, Germany. [Cohen, Shiri] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP O'Leary, KD (reprint author), SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. EM K.D.OLeary@stonybrook.edu NR 51 TC 5 Z9 5 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0194-472X EI 1752-0606 J9 J MARITAL FAM THER JI J. Marital Fam. Ther. PD OCT PY 2013 VL 39 IS 4 BP 502 EP 514 DI 10.1111/j.1752-0606.2012.00327.x PG 13 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 242HI UT WOS:000326229300009 PM 25800425 ER PT J AU Lee, J Hwang, YJ Kim, KY Kowall, NW Ryu, H AF Lee, Junghee Hwang, Yu Jin Kim, Ki Yoon Kowall, Neil W. Ryu, Hoon TI Epigenetic Mechanisms of Neurodegeneration in Huntington's Disease SO NEUROTHERAPEUTICS LA English DT Review DE DNA methylation; Histone code; Chromatin remodeling; Noncoding RNA; microRNA; Huntington's disease; Therapeutics ID HISTONE DEACETYLASE INHIBITORS; EMBRYONIC STEM-CELLS; WILD-TYPE HUNTINGTIN; MUTANT HUNTINGTIN; DNA METHYLATION; TRANSGENIC MICE; MOUSE MODEL; ALZHEIMERS-DISEASE; SODIUM-BUTYRATE; GENE-EXPRESSION AB Huntington's disease (HD) is an incurable and fatal hereditary neurodegenerative disorder of mid-life onset characterized by chorea, emotional distress, and progressive cognitive decline. HD is caused by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin gene. Recent studies suggest that epigenetic modifications may play a key role in HD pathogenesis. Alterations of the epigenetic "histone code" lead to chromatin remodeling and deregulation of neuronal gene transcription that are prominently linked to HD pathogenesis. Furthermore, specific noncoding RNAs and microRNAs are associated with neuronal damage in HD. In this review, we discuss how DNA methylation, post-translational modifications of histone, and noncoding RNA function are affected and involved in HD pathogenesis. In addition, we summarize the therapeutic effects of histone deacetylase inhibitors and DNA binding drugs on epigenetic modifications and neuropathological sequelae in HD. Our understanding of the role of these epigenetic mechanisms may lead to the identification of novel biological markers and new therapeutic targets to treat HD. C1 [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Hwang, Yu Jin; Kim, Ki Yoon; Ryu, Hoon] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, WCU Neurocyt Grp, Seoul 110799, South Korea. RP Ryu, H (reprint author), Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. EM hoonryu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIH NS [067283-02]; WCU Neurocytomics Program Grant [800-20080848]; SRC Grant from National Research Foundation [2010-0029-403]; Flagship Grant from KIST FX This study was supported by NIH NS 067283-02 (H. R.), WCU Neurocytomics Program Grant (800-20080848) (H. R.), and SRC Grant (2010-0029-403) (H. R.) from National Research Foundation, and Flagship Grant (H. R.) from KIST. NR 130 TC 19 Z9 21 U1 1 U2 34 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 OCT PY 2013 VL 10 IS 4 BP 664 EP 676 DI 10.1007/s13311-013-0206-5 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 242WR UT WOS:000326276300009 PM 24006238 ER PT J AU Nguyen, PL Hyatt, AS Devlin, PM AF Nguyen, Paul L. Hyatt, Andrew S. Devlin, Phillip M. TI PSA Screening: The Case in Favor SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID SERVICES TASK-FORCE; PROSTATE-CANCER; FOLLOW-UP; MORTALITY C1 [Nguyen, Paul L.; Hyatt, Andrew S.; Devlin, Phillip M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 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 OCT PY 2013 VL 27 IS 10 BP 980 EP + PG 2 WC Oncology SC Oncology GA 241AQ UT WOS:000326139200006 PM 24367854 ER PT J AU Aizer, AA D'Amico, AV AF Aizer, Ayal A. D'Amico, Anthony V. TI Should All Colorectal Cancer Patients Over Age 60 Be Screened for Prostate Cancer? SO ONCOLOGY-NEW YORK LA English DT Article ID RADICAL PROSTATECTOMY; RANDOMIZED PROSTATE; RECTAL-CANCER; FOLLOW-UP; TRIAL; ASSOCIATION; MORTALITY; RISK; RECOMMENDATION; COMORBIDITY AB Two large, randomized studies have demonstrated a prostate cancer-specific survival benefit to prostate cancer screening using the prostate-specific antigen (PSA) assay. Yet, the US Preventive Services Task Force recently recommended against PSA-based screening for prostate cancer, claiming it results in more harm than good, given concerns regarding overtreatment. The purpose of this article is to characterize the patients with colorectal cancer who are most likely to benefit from PSA-based screening for prostate cancer. Because the survival benefit due to PSA-based screening does not manifest until 7 years after screening is initiated, we conclude that PSA screening is most appropriate for men with a remaining life expectancy of at least 10 years. Accordingly, younger men with stage I-II colorectal cancers at diagnosis (or stage III colorectal cancer that has not recurred 5 years after treatment) who have no or minimal comorbidities and who are at increased risk for either a diagnosis of prostate cancer or mortality secondary to prostate cancer (patients who have a positive family history or are African-American, respectively) are most likely to experience more good outcomes than harmful ones as a result of undergoing PSA-based screening. C1 [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Aizer, AA (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St,ASB1,Level L2, Boston, MA 02115 USA. EM aaaizer@partners.org NR 35 TC 2 Z9 2 U1 0 U2 3 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2013 VL 27 IS 10 BP 1032 EP 1038 PG 7 WC Oncology SC Oncology GA 241AQ UT WOS:000326139200016 PM 24367864 ER PT J AU McCarthy, J Mc Millan, S AF McCarthy, Joseph Mc Millan, Sean TI Arthroscopy of the Hip: Factors Affecting Outcome SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article DE Hip arthroscopy; Survivorship; Osteoarthritis; Labral tear; Femoral acetabular impingement ID FEMORO-ACETABULAR IMPINGEMENT; 2-YEAR FOLLOW-UP; FEMOROACETABULAR IMPINGEMENT; LABRAL REPAIR; SURGERY; OSTEOARTHRITIS; AGE; DEBRIDEMENT; PREDICTORS; DYSPLASIA AB Hip arthroscopy is a rapidly progressing field that has advanced in function and survivorship over the past decade. As increasing literature is published on outcomes of hip arthroscopy, a retrospective review has allowed for the identification of factors that affect survivorship. Within this review, the authors present the factors identified to date that affect survivorship after hip arthroscopy while raising questions about the future direction of the field. C1 [McCarthy, Joseph] Massachusetts Gen Hosp, Newton Wellesley Hosp, Boston, MA 02114 USA. [Mc Millan, Sean] Our Lady Lourdes Hosp, Profess Orthoped Lourdes Med Associates, Burlington, NJ 08016 USA. RP Mc Millan, S (reprint author), Our Lady Lourdes Hosp, Profess Orthoped Lourdes Med Associates, 2103 Burlington Mt Holly Rd, Burlington, NJ 08016 USA. EM mcmillansean@hotmail.com NR 49 TC 9 Z9 9 U1 1 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 0030-5898 EI 1558-1373 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 2013 VL 44 IS 4 BP 489 EP + DI 10.1016/j.ocl.2013.06.002 PG 11 WC Orthopedics SC Orthopedics GA 242BB UT WOS:000326211300005 PM 24095065 ER PT J AU Chattergoon, NN Louey, S Stork, PJ Giraud, GD Thornburg, KL AF Chattergoon, N. N. Louey, S. Stork, P. J. Giraud, G. D. Thornburg, K. L. TI SURPRISING SIGNAL TRANSDUCTION CHANGES IN MATURING FETAL OVINE CARDIOMYOCYTES SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 [Chattergoon, N. N.; Louey, S.; Stork, P. J.; Giraud, G. D.; Thornburg, K. L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. [Louey, S.; Giraud, G. D.; Thornburg, K. L.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Chattergoon, N. N.; Louey, S.; Giraud, G. D.; Thornburg, K. L.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. [Stork, P. J.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. [Giraud, G. D.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 2013 VL 74 IS 4 BP 480 EP 480 PG 1 WC Pediatrics SC Pediatrics GA 239XT UT WOS:000326060000024 ER PT J AU Best, L Saxene, R Anderson, C Falcon, G Martin, C Castillo, B Keplin, K Pearson, N Lamb, F Bercier, S Keating, B AF Best, L. Saxene, R. Anderson, C. Falcon, G. Martin, C. Castillo, B. Keplin, K. Pearson, N. Lamb, F. Bercier, S. Keating, B. TI TWO VARIANTS OF THE C-REACTIVE PROTEIN GENE ARE ASSOCIATED WITH RISK OF PRE-ECLAMPSIA IN AN AMERICAN INDIAN POPULATION SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 [Best, L.; Falcon, G.; Martin, C.; Keplin, K.; Pearson, N.; Lamb, F.; Bercier, S.] Turtle Mt Community Coll, Belcourt, ND USA. [Saxene, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Anderson, C.] Univ N Dakota, Grand Forks, ND 58201 USA. [Castillo, B.; Keating, B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 2013 VL 74 IS 4 BP 481 EP 481 PG 1 WC Pediatrics SC Pediatrics GA 239XT UT WOS:000326060000035 ER PT J AU Ramani, S Orlander, JD AF Ramani, Subha Orlander, Jay D. TI Human Dimensions in Bedside Teaching: Focus Group Discussions of Teachers and Learners SO TEACHING AND LEARNING IN MEDICINE LA English DT Article DE bedside teaching; patient-centered teaching; physician-patient communication; clinical skills teaching ID CASE PRESENTATIONS; QUALITATIVE RESEARCH; ROUNDS; STUDENT; PATIENT; SENSE; CARE AB Background: Clinical teaching has moved from the bedside to conference rooms; many reasons are described for this shift. Yet, essential clinical skills, professionalism, and humanistic patient interactions are best taught at the bedside. Purpose: Clinical teaching has moved from the bedside to conference rooms; many reasons are described for this decline. This study explored perceptions of teachers and learners on the value of bedside teaching and the humanistic dimensions of bedside interactions that make it imperative to shift clinical teaching back to the bedside. Method: Focus group methodology was used to explore teacher and learner opinions. Four teacher groups consisted of (a) Chief Residents, (b) Residency Program Directors, (c) skilled bedside teachers, and (d) a convenience group of other Department of Medicine faculty at Boston University School of Medicine. Six learner groups consisted 2 each of 3rd-year students, PGY1 medicine residents, and PGY2 medicine residents. Each discussion lasted 60 to 90minutes. Sessions were audiotaped, transcribed, and analyzed using qualitative methods. Results: Teachers and learners shared several opinions on bedside teaching, particularly around humanistic aspects of bedside interactions. The key themes that emerged included (a) patient involvement in discussions, (b) teachers as role models of humanism, (c) preserving learner autonomy, (d) direct observation and feedback of learners at the bedside, (e) interactions with challenging patients, and (e) admitting limitations. Within these themes, participants noted some behaviors best avoided at the bedside. Conclusions: Teachers and learners regard the bedside as a valuable venue in which to learn core values of medicine. They proposed many strategies to preserve these humanistic values and improve bedside teaching. These strategies are essential for true patient-centered care. C1 [Ramani, Subha] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Orlander, Jay D.] Boston Univ, Sch Med, Dept Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Ramani, S (reprint author), Brigham & Womens Hosp, Phyllis Jen Ctr, Div Gen Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. EM sramani@partners.org NR 29 TC 0 Z9 0 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 EI 1532-8015 J9 TEACH LEARN MED JI Teach. Learn. Med. PD OCT 1 PY 2013 VL 25 IS 4 BP 312 EP 318 DI 10.1080/10401334.2013.827979 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 236IF UT WOS:000325788000006 PM 24112200 ER PT J AU Kadian-Dodov, DL van der Zee, SA Scott, SA Peter, I Martis, S Doheny, DO Rothlauf, EB Lubitz, SA Desnick, RJ Halperin, JL AF Kadian-Dodov, Daniella L. van der Zee, Sarina A. Scott, Stuart A. Peter, Inga Martis, Suparna Doheny, Dana O. Rothlauf, Elizabeth B. Lubitz, Steven A. Desnick, Robert J. Halperin, Jonathan L. TI Warfarin pharmacogenetics: A controlled dose-response study in healthy subjects SO VASCULAR MEDICINE LA English DT Article DE coagulation; CYP2C9; CYP4F2; dose-response; healthy subjects; pharmacogenetics; VKORC1; warfarin ID GENETICS COAG TRIAL; BLEEDING COMPLICATIONS; DOSING ALGORITHMS; OPTIMAL ANTICOAGULATION; VKORC1; CYP2C9; GENOTYPE; THERAPY; POLYMORPHISM; ASSOCIATION AB The aim of this study was to determine how genetic variants contribute to warfarin dosing variability when non-genetic factors are controlled. Thirty healthy subjects were subjected to a warfarin dosing algorithm with daily international normalized ratio (INR) measurements to INR 2.0, then off warfarin to INR 1.2. The primary outcome was the cumulative dose required to achieve INR 2.0 for 2 consecutive days. CYP2C9 (p=0.004) and VKORC1 (p=0.02) variant carriers required lower cumulative doses, and CYP4F2 carriers required higher doses (p=0.04). Subjects with variants in both CYP2C9 and VKORC1 required fewer days to reach INR 2.0 than wild-type subjects or those with variants in CYP2C9 or VKORC1 (p=0.01). Genetic contribution to dose variability (similar to 62%) was greater than previously reported, suggesting that uncontrolled clinical variables influence the effect of these variants. In conclusion, genotype-guided warfarin-dosing algorithms may rely more on genetic variables in healthier individuals than in patients with clinical confounders. ClinicalTrials.gov Identifier: NCT01520402 C1 [Kadian-Dodov, Daniella L.] Icahn Sch Med Mt Sinai, Vasc Med Sect, Zena & Michael Wiener Cardiovasc Inst, New York, NY 10029 USA. [van der Zee, Sarina A.] Pacific Heart Inst, Santa Monica, CA USA. [Scott, Stuart A.; Peter, Inga; Martis, Suparna; Doheny, Dana O.; Desnick, Robert J.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Rothlauf, Elizabeth B.; Halperin, Jonathan L.] Icahn Sch Med Mt Sinai, Zena & Michael Wiener Cardiovasc Inst, New York, NY 10029 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv & Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. RP Kadian-Dodov, DL (reprint author), Icahn Sch Med Mt Sinai, Cardiovasc Inst, Box 1030 Mt Sinai Med Ctr,1 Gustave L Levy Pl, New York, NY 10029 USA. EM daniella.kadian-dodov@mssm.edu FU Icahn School of Medicine at Mount Sinai [GCO] [08-1442] FX This work was supported by the Icahn School of Medicine at Mount Sinai [GCO# 08-1442]. NR 36 TC 2 Z9 2 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD OCT PY 2013 VL 18 IS 5 BP 290 EP 297 DI 10.1177/1358863X13503193 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 242IJ UT WOS:000326232200007 PM 24029542 ER PT J AU Shapiro, S Traiger, G Hill, W Zhang, LX Doran, AK AF Shapiro, Shelley Traiger, Glenna Hill, Wendy Zhang, Lixia Doran, Aimee K. TI Safety, Tolerability, and Efficacy of Overnight Switching From Sildenafil to Tadalafil in Patients With Pulmonary Arterial Hypertension SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE Tadalafil; Retrospective; Transition; Sildenafil; Pulmonary arterial hypertension; Phosphodiesterase type 5 inhibitor ID THERAPY; PHARMACOKINETICS AB SummaryAims Tadalafil, a once-daily phosphodiesterase type 5 inhibitor (PDE-5I), offers clinicians an alternative to sildenafil, a 3-times-daily (t.i.d.) PDE-5I for treatment of pulmonary arterial hypertension (PAH). However, there are limited data describing the risks and benefits or recommended methodology of switching patients from sildenafil to tadalafil. Methods Chart reviews were conducted on all World Health Organization group 1 patients on sildenafil for >= 3 months who transitioned to tadalafil with documented clinic visits and 6-min walk tests on both drugs. Most patients were transitioned by discontinuing sildenafil after the evening dose and initiating tadalafil 40 mg/day the next day. Data collected included demographics, PAH etiology, diagnostic hemodynamics, 6-min walk distance (6MWD), PDE-5I side effects, and concomitant medications. Data on B-type natriuretic peptide (BNP) levels were available for most patients also receiving endothelin receptor antagonists (ERAs). Results Medical records from 98 patients were evaluated. Most patients (92%) were on sildenafil for > 1 year, and 78% were receiving sildenafil 80-100 mg t.i.d. Ninety-seven percent of patients (95/98) were successfully transitioned and maintained on 40 mg/day. With a mean duration on tadalafil therapy of 243 +/- 127 days at the time of analysis, 6MWD was unchanged. Patient-reported adverse events included headache (4%) and heartburn (2%). There was minimal change in BNP levels in the subset of patients receiving an ERA concomitantly. Conclusions Transition from sildenafil to tadalafil 40 mg/day appears feasible without clinical deterioration or intolerable side effects. This study provides guidance to physicians considering transition from sildenafil to tadalafil for selecting patients. C1 [Shapiro, Shelley; Hill, Wendy] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. [Shapiro, Shelley; Traiger, Glenna; Hill, Wendy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zhang, Lixia; Doran, Aimee K.] United Therapeut Corp, Res Triangle Pk, NC USA. RP Shapiro, S (reprint author), Greater Los Angeles VA Healthcare Syst, Cardiol Sect 111E, 11301 Wilshire Blvd Bldg 500, Los Angeles, CA 90073 USA. EM Shelley.Shapiro@va.gov FU United Therapeutics FX The site's principal investigators prepared the manuscript without compensation. Assistance with medical writing and editing was provided under the direction of the authors by Larry Nelson and Chris Lawrence, MedThink SciCom, with support from United Therapeutics. Funding was received from United Therapeutics to help supply staff for data collection, for statistician, and for poster and manuscript preparation. The principal investigator received funding from United Therapeutics for other pulmonary hypertension-related studies. NR 16 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5914 EI 1755-5922 J9 CARDIOVASC THER JI Cardiovasc. Ther. PD OCT PY 2013 VL 31 IS 5 BP 274 EP 279 DI 10.1111/1755-5922.12038 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 216RY UT WOS:000324302900007 PM 23841794 ER PT J AU Uraizee, I Cheng, S Hung, CL Verma, A Thomas, JD Zile, MR Aurigemma, GP Solomon, SD AF Uraizee, Imran Cheng, Susan Hung, Chung-Lieh Verma, Anil Thomas, James D. Zile, Michael R. Aurigemma, Gerard P. Solomon, Scott D. TI Relation of N-Terminal Pro-B-Type Natriuretic Peptide With Diastolic Function in Hypertensive Heart Disease SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; diastolic function; hypertension; imaging; natriuretic peptides; speckle-tracking echocardiography; strain ID VENTRICULAR SYSTOLIC DYSFUNCTION; BLOOD-PRESSURE; CYCLIC-GMP; FAILURE; AGE; ECHOCARDIOGRAPHY; HYPERTROPHY; ASSOCIATION; RECEPTOR; RECOMMENDATIONS AB BACKGROUND Elevated natriuretic peptide levels in asymptomatic individuals without heart failure are associated with increased risk of adverse cardiovascular outcomes and may reflect subclinical cardiac dysfunction. METHODS In a sample of 313 asymptomatic individuals (51% women, mean age 61 years) with hypertension and diastolic dysfunction, we examined the association of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) with both conventional and advanced echocardiographic measures of systolic and diastolic function, including myocardial strain, using speckle-tracking-based analyses. RESULTS In univariate analyses, higher NT-proBNP was associated with greater left ventricular mass index (P = 0.003), left atrial volume index (P = 0.007), lateral E' velocity (P < 0.0001), E/E' ratio (P < 0.0001), peak global longitudinal systolic strain (P = 0.015), systolic strain rate (P = 0.021), and early diastolic strain rate (P < 0.0001). In multivariable analyses, NT-proBNP remained associated with measures of diastolic dysfunction, including lateral E' velocity (P = 0.013) and the E/E' ratio (P = 0.008). However, early diastolic strain rate was the echocardiographic parameter most strongly associated with NT-proBNP (P = 0.003). CONCLUSIONS In the setting of asymptomatic hypertensive heart disease and preserved ejection fraction, elevation in natriuretic peptide levels is predominantly associated with subclinical diastolic dysfunction. C1 [Uraizee, Imran; Cheng, Susan; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Hung, Chung-Lieh] Mackay Mem Hosp, Taipei, Taiwan. [Verma, Anil] Ochsner Clin Fdn, Dept Cardiol, New Orleans, LA USA. [Thomas, James D.] Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. [Zile, Michael R.] Ralph H Johnson Dept VA Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Aurigemma, Gerard P.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu FU Novartis Pharmaceuticals FX The original clinical trial was funded by Novartis Pharmaceuticals. NR 40 TC 4 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 2013 VL 26 IS 10 BP 1234 EP 1241 DI 10.1093/ajh/hpt098 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 239TF UT WOS:000326047700014 PM 23792241 ER PT J AU Smoller, JW AF Smoller, Jordan W. TI Disorders and Borders: Psychiatric Genetics and Nosology SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE psychiatric; genetic; nosology; pleiotropy; cross-disorder ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; AUTISM SPECTRUM DISORDERS; ENVIRONMENTAL RISK-FACTORS; GENOME-WIDE ASSOCIATION; CARDIO-FACIAL SYNDROME; POPULATION-BASED TWIN; DEFAULT MODE NETWORK; DEFICIT HYPERACTIVITY DISORDER; SUPPORTED PSYCHOSIS VARIANT AB Over the past century, the definition and classification of psychiatric disorders has evolved through a combination of historical trends, clinical observations, and empirical research. The current nosology, instantiated in the DSM-5 and ICD-10, rests on descriptive criteria agreed upon by a consensus of experts. While the development of explicit criteria has enhanced the reliability of diagnosis, the validity of the current diagnostic categories has been the subject of debate and controversy. Genetic studies have long been regarded as a key resource for validating the boundaries among diagnostic categories. Genetic epidemiologic studies have documented the familiality and heritability of clinically defined psychiatric disorders and molecular genetic studies have begun to identify specific susceptibility variants. At the same time, there is growing evidence from family, twin and genomic studies that genetic influences on psychiatric disorders transcend clinical boundaries. Here I review this evidence for cross-disorder genetic effects and discuss the implications of these findings for psychiatric nosology. Psychiatric genetic research can inform a bottom-up reappraisal of psychopathology that may help the field move beyond a purely descriptive classification and toward an etiology-based nosology. (c) 2013 Wiley Periodicals, Inc. C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 283 TC 9 Z9 9 U1 8 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 559 EP 578 DI 10.1002/ajmg.b.32174 PG 20 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500002 PM 24132891 ER PT J AU Thermenos, HW Keshavan, MS Juelich, RJ Molokotos, E Whitfield-Gabrieli, S Brent, BK Makris, N Seidman, LJ AF Thermenos, H. W. Keshavan, M. S. Juelich, R. J. Molokotos, E. Whitfield-Gabrieli, S. Brent, B. K. Makris, N. Seidman, L. J. TI A Review of Neuroimaging Studies of Young Relatives of Individuals With Schizophrenia: A Developmental Perspective From Schizotaxia to Schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE schizophrenia; MRI; high-risk; neuroimaging; genetics ID HIGH GENETIC RISK; CHILDHOOD-ONSET SCHIZOPHRENIA; MAGNETIC-RESONANCE-SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; COGNITIVE ENHANCEMENT THERAPY; SUPERIOR TEMPORAL GYRUS; WHITE-MATTER INTEGRITY; ADOLESCENT HIGH-RISK; BIPOLAR DISORDER; NONPSYCHOTIC SIBLINGS AB In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of schizotaxia, and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) high-risk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments. (c) 2013 Wiley Periodicals, Inc. C1 [Thermenos, H. W.; Keshavan, M. S.; Brent, B. K.; Makris, N.; Seidman, L. J.] Harvard Univ, Sch Med, Boston, MA USA. [Thermenos, H. W.; Keshavan, M. S.; Brent, B. K.; Seidman, L. J.] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Thermenos, H. W.; Keshavan, M. S.; Molokotos, E.; Brent, B. K.; Seidman, L. J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Thermenos, H. W.; Juelich, R. J.; Brent, B. K.; Makris, N.; Seidman, L. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Whitfield-Gabrieli, S.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, S.] MIT, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Makris, N.] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, N.] Massachusetts Gen Hosp, Dept Radiol, Ctr Morphometr Anal, Boston, MA 02114 USA. RP Thermenos, HW (reprint author), Athinoula Martinos Ctr Biomed Imaging, Bldg 149,2nd Floor Room 2602E,13th St, Charlestown, MA 02129 USA. EM hthermen@bidmc.harvard.edu FU NIMH [MH081928, MH065571, MH092840, RO1 MH064023, MH078113, KO2 01180]; Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006] FX Grant sponsor: NIMH; Grant numbers: MH081928, MH065571, MH092840, RO1 MH064023, MH078113, KO2 01180; Grant sponsor: Commonwealth Research Center of the Massachusetts Department of Mental Health; Grant number: SCDMH82101008006. NR 235 TC 34 Z9 35 U1 4 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 604 EP 635 DI 10.1002/ajmg.b.32170 PG 32 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500006 PM 24132894 ER PT J AU Buka, SL Seidman, LJ Tsuang, MT Goldstein, JM AF Buka, Stephen L. Seidman, Larry J. Tsuang, Ming T. Goldstein, Jill M. TI The New England Family Study High-Risk Project: Neurological Impairments Among Offspring of Parents With Schizophrenia and Other Psychoses SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE epidemiology; psychosis; etiology; risk factors; prospective ID CHILDHOOD; CHILDREN; ABNORMALITIES; TRANSMISSION; ADOLESCENCE; DEVIATION; MOTHERS; BIRTH AB This manuscript presents the design and initial outcomes of the New England Family Study's (NEFS) High-Risk Project, one of the few epidemiologically representative cohorts that has prospectively followed a large sample of offspring of parents with both affective and non-affective psychotic disorders from the fetal period forward. The goals of this report are: (1) to describe in some detail the design, data collection methods, and resulting sample of this project; and (2) to prospectively identify and compare rates of childhood neurological impairments among offspring of psychotic and nonpsychotic parents, with a particular emphasis on offspring risk in relation to specific classes of parental psychosis (i.e., affective vs. non-affective psychosis). The investigators identified a pool of 755 parents with potential psychotic disorders, located over 80% of these and confirmed psychotic diagnoses for 212 affected parents and 132 unaffected control parents. At birth, the 259 offspring of parents with psychosis had approximately a twofold increased risk of abnormal neurological functioning compared to offspring of families with no psychotic history. This was most pronounced among the 58 offspring of parents with schizophrenia. Similar trends were observed at ages 1 and 7 years although these did not reach statistical significance. Neither at birth nor at any of the follow-up assessments were the 157 offspring of parents with affective psychosis found to be at elevated risk of neurological impairment. Implications for future research and potential preventive interventions for at-risk individuals are discussed. (c) 2013 Wiley Periodicals, Inc. C1 [Buka, Stephen L.] Brown Univ, Dept Epidemiol, Providence, RI 02810 USA. [Seidman, Larry J.; Goldstein, Jill M.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Seidman, Larry J.; Tsuang, Ming T.; Goldstein, Jill M.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Boston, MA 02115 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Goldstein, Jill M.] Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth, Boston, MA USA. [Goldstein, Jill M.] BWH Dept Psychiat, Boston, MA USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Buka, SL (reprint author), Brown Univ, Dept Epidemiol, 121 South Main St, Providence, RI 02810 USA. EM sbuka@brown.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH [RO1 MH50647]; Stanley Medical Research Institute FX Work for this study was supported by NIMH RO1 MH50647 (1999-2003, Tsuang, P. I.; 2003-2006, Goldstein, P. I.), and the Stanley Medical Research Institute (Buka, P. I.). The authors would like to express their appreciation to the dedicated NEFS research team including Jasmina Burdzovic-Andreas, Ph.D.; Sara Cherkerzian, Sc.D., Lisa Denny, M. D.; Jo-Ann Donatelli, Ph.D., Christiana Provencal, M. A.; Anne Remington, M. A., and to the sustained involvement and many contributions of the NEFS study participants. NR 35 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 653 EP 660 DI 10.1002/ajmg.b.32181 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500009 PM 24132897 ER PT J AU Goldstein, JM Cherkerzian, S Tsuang, MT Petryshen, TL AF Goldstein, Jill M. Cherkerzian, Sara Tsuang, Ming T. Petryshen, Tracey L. TI Sex Differences in the Genetic Risk for Schizophrenia: History of the Evidence for Sex-Specific and Sex-Dependent Effects SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE hormones; psychoses; sex-specificity; sex chromosomes; genetic transmission ID GENOME-WIDE ASSOCIATION; BIPOLAR AFFECTIVE-DISORDER; X-CHROMOSOME MARKERS; PSEUDOAUTOSOMAL LOCUS; LINKAGE ANALYSIS; SUSCEPTIBILITY LOCUS; FAMILIAL RISK; SCHIZOAFFECTIVE DISORDER; POTENTIAL LINKAGE; SIBLING PAIRS AB Although there is a long history to examinations of sex differences in the familial (and specifically, genetic) transmission of schizophrenia, there have been few investigators who have systematically and rigorously studied this issue. This is true even in light of population and clinical studies identifying significant sex differences in incidence, expression, neuroanatomic and functional brain abnormalities, and course of schizophrenia. This review highlights the history of work in this arena from studies of family transmission patterns, linkage and twin studies to the current molecular genetic strategies of large genome-wide association studies. Taken as a whole, the evidence supports the presence of genetic risks of which some are sex-specific (i.e., presence in one sex and not the other) or sex-dependent (i.e., quantitative differences in risk between the sexes). Thus, a concerted effort to systematically investigate these questions is warranted and, as we argue here, necessary in order to fully understand the etiology of schizophrenia. (c) 2013 Wiley Periodicals, Inc. C1 [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Dept Psychiat, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Cherkerzian, Sara; Petryshen, Tracey L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.; Cherkerzian, Sara] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, Jill M.; Tsuang, Ming T.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Tsuang, Ming T.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA USA. [Tsuang, Ming T.] Harvard Univ, Sch Med, Boston, MA USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Petryshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1 Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu FU NIMH [RO1 MH50647, RO1 MH56956] FX Grant sponsor: NIMH; Grant numbers: RO1 MH50647; RO1 MH56956. NR 153 TC 15 Z9 15 U1 6 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 698 EP 710 DI 10.1002/ajmg.b.32159 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500014 PM 24132902 ER PT J AU Kotte, A Faraone, SV Biederman, J AF Kotte, Amelia Faraone, Stephen V. Biederman, Joseph TI Association of Genetic Risk Severity With ADHD Clinical Characteristics SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetic risk alleles; genetic risk severity; attention deficit disorder (ADD); attention-deficit; hyperactivity disorder (ADHD); DRD4; DAT1; SERT; 5-HTTLPR ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; GENOME-WIDE ASSOCIATION; SEROTONIN TRANSPORTER GENE; CATECHOL-O-METHYLTRANSFERASE; OPPOSITIONAL DEFIANT DISORDER; DOPAMINE-D4 RECEPTOR GENE; EMOTIONAL SELF-REGULATION; FAMILY-BASED ASSOCIATION; CONDUCT DISORDER AB This study sought to examine the association between the cumulative risk severity conferred by the total number of attention-deficit/hyperactivity disorder (ADHD) risk alleles of the DAT1 3UTR variable number tandem repeat (VNTR), DRD4 Exon 3 VNTR, and 5-HTTLPR with ADHD characteristics, clinical correlates, and functional outcomes in a pediatric sample. Participants were derived from case-control family studies of boys and girls diagnosed with ADHD, a genetic linkage study of families with children with ADHD, and a family genetic study of pediatric bipolar disorder. Caucasian children 18 and younger with and without ADHD and with available genetic data were included in this analysis (N=591). The association of genetic risk severity with sociodemographic, clinical characteristics, neuropsychological, emotional, and behavioral correlates was examined in the entire sample, in the sample with ADHD, and in the sample without ADHD, respectively. Greater genetic risk severity was significantly associated with the presence of disruptive behavior disorders in the entire sample and oppositional defiant disorder in participants with ADHD. Greater genetic risk severity was also associated with the absence of anxiety disorders, specifically with the absence of agoraphobia in the context of ADHD. Additionally, one ADHD symptom was significantly associated with greater genetic risk severity. Genetic risk severity is significantly associated with ADHD clinical characteristics and co-morbid disorders, and the nature of these associations may vary on the type (externalizing vs. internalizing) of the disorder. (c) 2013 Wiley Periodicals, Inc. C1 [Kotte, Amelia; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Kotte, Amelia; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Kotte, Amelia; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Clin & Res Program Pediat Psychopharmacol, YAW 6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Kotte, Amelia/0000-0002-0198-7914; Faraone, Stephen/0000-0002-9217-3982 FU NIH [R01HD037694, R01HD037999, R01MH066877, R01MH050657, R01HD036317, R01MH066237] FX Grant sponsor: NIH; Grant numbers: R01HD037694; R01HD037999; R01MH066877; R01MH050657; R01HD036317; R01MH066237. NR 97 TC 6 Z9 6 U1 6 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 718 EP 733 DI 10.1002/ajmg.b.32171 PG 16 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500016 PM 24132904 ER PT J AU Chang, SC Pauls, DL Lange, C Sasanfar, R Santangelo, SL AF Chang, Shun-Chiao Pauls, David L. Lange, Christoph Sasanfar, Roksana Santangelo, Susan L. TI Sex-Specific Association of a Common Variant of the XG Gene With Autism Spectrum Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE autism; GWAS; sex-specific; pseudoautosomal ID HUMAN PSEUDOAUTOSOMAL REGIONS; GENOME-WIDE ASSOCIATION; RISK; LINKAGE; CD99; SCHIZOPHRENIA; CHILDREN; ALLELES; LOCUS; BRAIN AB Autism spectrum disorders (ASD) are much more common in males than in females. Studies using both linkage and candidate gene association approaches have identified genetic variants specific to families in which all affected cases were male, suggesting that sex may interact with or otherwise influence the expression of specific genes in association with ASD. In this study, we specifically evaluated the sex-specific genetic effects of ASD with a family-based genome-wide association study approach using the data from the Autism Genetic Resource Exchange repository. We evaluated the male-specific genetic effects of ASD in 374 multiplex families of European ancestry in which all affected were male (male-only; MO) and identified a novel genome-wide significant association in the pseudoautosomal boundary on chromosome Xp22.33/Yp11.31 in the MO families of predominantly paternal origin (rs2535443, p=3.8x10(-8)). Five markers that reside within a 550kb intergenic region on chromosome 13q33.3, between the MYO16 and IRS2 genes, also showed suggestive association with ASD in the MO families (p=3.3x10(-5) to 5.3x10(-7)). In contrast, none of these markers appeared to be associated with ASD in the families containing any affected females. Our results suggest that the pseudoautosomal boundary on Xp22.33/Yp11.31 may harbor male-specific genetic variants for ASD. (c) 2013 Wiley Periodicals, Inc. C1 [Chang, Shun-Chiao; Pauls, David L.; Santangelo, Susan L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chang, Shun-Chiao] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Pauls, David L.; Sasanfar, Roksana; Santangelo, Susan L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.; Sasanfar, Roksana; Santangelo, Susan L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lange, Christoph] Brigham & Womens Hosp, Channing Labs, Boston, MA 02115 USA. [Lange, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [Lange, Christoph] Univ Bonn, Inst Genom Math, Bonn, Germany. [Lange, Christoph] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Santangelo, Susan L.] Maine Med Ctr, Res Inst, Dept Psychiat, Portland, ME 04102 USA. RP Santangelo, SL (reprint author), Maine Med Ctr, 932 Congress St,Rm 224, Portland, ME 04102 USA. EM SSantangel@mmc.org FU AGRE Consortium; National Institute of Mental Health [1U24MH081810] FX Grant sponsor: AGRE Consortium; Grant sponsor: National Institute of Mental Health; Grant number: 1U24MH081810. NR 57 TC 7 Z9 7 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 742 EP 750 DI 10.1002/ajmg.b.32165 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500018 PM 24132906 ER PT J AU Fung, WLA Naylor, MG Bennett, DA Lange, C Blacker, D AF Fung, Wai Lun Alan Naylor, Melissa G. Bennett, David A. Lange, Christoph Blacker, Deborah TI Principal Components Methods for Narrow-Sense Heritability in the Analysis of Multidimensional Longitudinal Cognitive Phenotypes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE principal components of heritability; multidimensional longitudinal data; cognitive decline; neuropsychological tests ID GENOME-WIDE ASSOCIATION; CHANGE-POINT MODEL; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; IDENTIFIES VARIANTS; EPSILON-4 ALLELE; COMMON VARIANTS; APOE EPSILON-4; OLDER PERSONS; IMPAIRMENT AB BackgroundGenetic association studies of longitudinal cognitive phenotypes are an alternate approach to discovering genetic risk factors for Alzheimer's disease (AD). However, the standard linear mixed model approach is limited in the face of multidimensional longitudinal data and multiple genotypes. In this setting, the principal components of heritability (PCH) approach may increase efficiency by deriving a linear combination of phenotypes to maximize the heritability attributable to a particular genetic locus. The current study investigated the performance of two PCH methods, the Principal Components of Heritability Association Test (PCHAT) and C2BAT, in detecting association of the known AD susceptibility allele APOE-E4 with cognitive function at baseline and decline in cognition over time. MethodsPCHAT, C2BAT, and standard linear mixed models were used to test for association between APOE-E4 allele and performance on 19 neuropsychological tests using subjects without dementia at baseline from the Religious Orders Study (ROS) (n=693) and Memory and Aging Project (MAP) (n=778). Analyses were conducted across the three methods for three nested phenotype definitions (all 19 measures, executive function and episodic memory measures, and episodic memory only), and for baseline data only versus longitudinal change. ResultsIn all cases, APOE-E4 was significantly associated with baseline level of and change over time in cognitive function, and PCHAT and C2BAT yielded evidence of association comparable to or stronger than conventional methods. ConclusionPCHAT, C2BAT, and other PCH methods may have utility for genetic association studies of multidimensional cognitive and other phenotypes by maximizing genetic information while limiting multiple comparisons. Copyright (c) 2013 Wiley Periodicals, Inc. C1 [Fung, Wai Lun Alan; Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02129 USA. [Fung, Wai Lun Alan] Univ Toronto, Fac Med, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [Naylor, Melissa G.; Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02129 USA. [Naylor, Melissa G.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Lange, Christoph] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. RP Blacker, D (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Massachusetts Gen Hosp, Dept Psychiat,Sch Med, 149 13th St,149-2691, Boston, MA 02129 USA. FU Alzheimer's Association Grant; Harvard University; National Institute of Mental Health [T32MH017119]; National Institute on Aging [P30AG10161, R01AG15819, R01AG17917] FX Grant sponsor: Alzheimer's Association Grant; Grant sponsor: Harvard University scholarship; Grant sponsor: National Institute of Mental Health Training Grant; Grant number: T32MH017119; Grant sponsor: National Institute on Aging Grants; Grant numbers: P30AG10161, R01AG15819, R01AG17917. NR 45 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2013 VL 162 IS 7 SI SI BP 770 EP 778 DI 10.1002/ajmg.b.32151 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 238WN UT WOS:000325982500021 PM 23650207 ER PT J AU Wang, ZJ Subramanya, AR Satlin, LM Pastor-Soler, NM Carattino, MD Kleyman, TR AF Wang, Zhijian Subramanya, Arohan R. Satlin, Lisa M. Pastor-Soler, Nuria M. Carattino, Marcelo D. Kleyman, Thomas R. TI Regulation of large-conductance Ca2+-activated K+ channels by WNK4 kinase SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE BK channel; familial hyperkalemic hypertension; Maxi-K; With-no-lysine kinase 4; WNK4 ID CORTICAL COLLECTING DUCT; POTASSIUM CHANNELS; APICAL MEMBRANE; CONNECTING TUBULE; INTERCALATED CELLS; SURFACE EXPRESSION; BARTTERS-SYNDROME; DISTAL NEPHRON; ALPHA-SUBUNIT; ROMK AB Large-conductance, Ca2+-activated K+ channels, commonly referred to as BK channels, have a major role in flow-induced K+ secretion in the distal nephron. With-no-lysine kinase 4 (WNK4) is a serine-threonine kinase expressed in the distal nephron that inhibits ROMK activity and renal K+ secretion. WNK4 mutations have been described in individuals with familial hyperkalemic hypertension (FHHt), a Mendelian disorder characterized by low-renin hypertension and hyperkalemia. As BK channels also have an important role in renal K+ secretion, we examined whether they are regulated by WNK4 in a manner similar to ROMK. BK channel activity was inhibited in a rabbit intercalated cell line transfected with WNK4 or a WNK4 mutant found in individuals with FHHt. Coexpression of an epitope-tagged BK alpha-subunit with WNK4 or the WNK4 mutant in HEK293 cells reduced BK alpha-subunit plasma membrane and whole cell expression. A region within WNK4 encompassing the autoinhibitory domain and a coiled coil domain was required for WNK4 to inhibit BK alpha-subunit expression. The relative fraction of BK alpha-subunit that was ubiquitinated was significantly increased in cells expressing WNK4, compared with controls. Our results suggest that WNK4 inhibits BK channel activity, in part, by increasing channel degradation through an ubiquitin-dependent pathway. Based on these results, we propose that WNK4 provides a cellular mechanism for the coordinated regulation of two key secretory K+ channels in the distal nephron, ROMK and BK. C1 [Wang, Zhijian; Subramanya, Arohan R.; Pastor-Soler, Nuria M.; Carattino, Marcelo D.; Kleyman, Thomas R.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Subramanya, Arohan R.; Pastor-Soler, Nuria M.; Carattino, Marcelo D.; Kleyman, Thomas R.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA USA. [Satlin, Lisa M.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY USA. [Subramanya, Arohan R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Carattino, MD (reprint author), Dept Med, Renal Electrolyte Div, S828 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM mdc4@pitt.edu FU National Institutes of Health [R01 DK-038470, R01 DK-084184, R37 DK-051391, T32 DK-061296, P30 DK0-79307] FX This work was supported by grants from the National Institutes of Health, including R01 DK-038470, R01 DK-084184, R37 DK-051391, T32 DK-061296, and P30 DK0-79307 (Pittsburgh Center for Kidney Research, Univ. of Pittsburgh). NR 48 TC 12 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2013 VL 305 IS 8 BP C846 EP C853 DI 10.1152/ajpcell.00133.2013 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 237KV UT WOS:000325869700006 PM 23885063 ER PT J AU Hobai, IA Buys, ES Morse, JC Edgecomb, J Weiss, EH Armoundas, AA Hou, XY Khandelwal, AR Siwik, DA Brouckaert, P Cohen, RA Colucci, WS AF Hobai, Ion A. Buys, Emmanuel S. Morse, Justin C. Edgecomb, Jessica Weiss, Eric H. Armoundas, Antonis A. Hou, Xiuyun Khandelwal, Alok R. Siwik, Deborah A. Brouckaert, Peter Cohen, Richard A. Colucci, Wilson S. TI SERCA Cys(674) sulphonylation and inhibition of L-type Ca2+ influx contribute to cardiac dysfunction in endotoxemic mice, independent of cGMP synthesis SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiomyopathy; sepsis; sarcoplasmic reticulum; contractility; oxidative stress; sarco(endo)plasmic reticulum Ca2+-ATPase; cysteine ID PREVENTS MYOCARDIAL DYSFUNCTION; INDUCED CONTRACTILE DYSFUNCTION; NITRIC-OXIDE; SARCOPLASMIC-RETICULUM; SEPTIC SHOCK; VENTRICULAR MYOCYTES; ACTIVATES SERCA; CALCIUM-UPTAKE; HEART-FAILURE; CYCLIC-GMP AB The goal of this study was to identify the cellular mechanisms responsible for cardiac dysfunction in endotoxemic mice. We aimed to differentiate the roles of cGMP [produced by soluble guanylyl cyclase (sGC)] versus oxidative posttranslational modifications of Ca2+ transporters. C57BL/6 mice [wild-type (WT) mice] were administered lipopolysaccharide (LPS; 25 mu g/g ip) and euthanized 12 h later. Cardiomyocyte sarcomere shortening and Ca2+ transients (Delta Ca-i) were depressed in LPS-challenged mice versus baseline. The time constant of Ca2+ decay (tau(Ca)) was prolonged, and sarcoplasmic reticulum Ca2+ load (Ca-SR) was depressed in LPS-challenged mice (vs. baseline), indicating decreased activity of sarco(endo)plasmic Ca2+-ATPase (SERCA). L-type Ca2+ channel current (I-Ca,I-L) was also decreased after LPS challenge, whereas Na+/Ca2+ exchange activity, ryanodine receptors leak flux, or myofilament sensitivity for Ca2+ were unchanged. All Ca2+-handling abnormalities induced by LPS (the decrease in sarcomere shortening, Delta Cai, CaSR, ICa, L, and tau(Ca) prolongation) were more pronounced in mice deficient in the sGC main isoform (sGC alpha(-/-)(1) mice) versus WT mice. LPS did not alter the protein expression of SERCA and phospholamban in either genotype. After LPS, phospholamban phosphorylation at Ser(16) and Thr(17) was unchanged in WT mice and was increased in sGC alpha(-/-)(1) mice. LPS caused sulphonylation of SERCA Cys(674) (as measured immunohistochemically and supported by iodoacetamide labeling), which was greater in sGC alpha(-/-)(1) versus WT mice. Taken together, these results suggest that cardiac Ca2+ dysregulation in endotoxemic mice is mediated by a decrease in L-type Ca2+ channel function and oxidative posttranslational modifications of SERCA Cys(674), with the latter (at least) being opposed by sGC-released cGMP. C1 [Hobai, Ion A.; Morse, Justin C.; Edgecomb, Jessica; Siwik, Deborah A.; Colucci, Wilson S.] Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Hobai, Ion A.; Buys, Emmanuel S.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Weiss, Eric H.; Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Hou, Xiuyun; Khandelwal, Alok R.; Cohen, Richard A.] Boston Univ, Med Ctr, Dept Med, Vasc Biol Sect, Boston, MA 02118 USA. [Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Brouckaert, Peter] Flanders Inst Biotechnol, Dept Mol Biomed Res, Ghent, Belgium. RP Hobai, IA (reprint author), Boston Univ, Med Ctr, Evans Basic Res Bldg,650 Albany St, Boston, MA 02118 USA. EM ihobai@partners.org FU National Institutes of Health (NIH) [HL-061639, HL-064750, HL-31607]; NIH [N01-HV-28178]; National Institutes of Health [K08-GM-096082, T32-GM-007592]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; American Heart Association [10SDG2610313, 0635127N, 0815767D]; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Cardiovascular Research Society; Boston University FX This work was supported by National Institutes of Health (NIH) Grants HL-061639 (to W. S. Colucci), HL-064750 (to W. S. Colucci), and HL-31607 (to R. A. Cohen) and by the NIH-sponsored Boston University Cardiovascular Proteomics Center (Contract No. N01-HV-28178, to W. S. Colucci). I. A. Hobai acknowledges support from National Institutes of Health Grants K08-GM-096082 and T32-GM-007592 and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. Other support includes American Heart Association Grants 10SDG2610313 (to E S. Buys), 0635127N (to A. A. Armoundas), and 0815767D (to E. H. Weiss), the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke (to A. A. Armoundas), the Cardiovascular Research Society (to A. A. Armoundas), and Boston University (Student Research Awards to J. C. Morse and J. Edgecomb). NR 41 TC 7 Z9 7 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2013 VL 305 IS 8 BP H1189 EP H1200 DI 10.1152/ajpheart.00392.2012 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237KM UT WOS:000325868600009 PM 23934853 ER PT J AU Ruddy, KJ Desantis, SD Gelman, RS Wu, AHB Punglia, RS Mayer, EL Tolaney, SM Winer, EP Partridge, AH Burstein, HJ AF Ruddy, Kathryn J. Desantis, Stephen D. Gelman, Rebecca S. Wu, Alan H. B. Punglia, Rinaa S. Mayer, Erica L. Tolaney, Sara M. Winer, Eric P. Partridge, Ann H. Burstein, Harold J. TI Personalized medicine in breast cancer: tamoxifen, endoxifen, and CYP2D6 in clinical practice SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast neoplasms; Genotype; Antineoplastic agents/hormonal; Tamoxifen ID HOT FLASHES; METABOLITE CONCENTRATIONS; GENOTYPE; TRIAL; WOMEN; THERAPY; POLYMORPHISMS; EFFICACY; OUTCOMES; COHORT AB Tamoxifen is metabolized into endoxifen, a potent antagonist of the estrogen receptor, in part through cytochrome p450 (CYP) 2D6. Genotypic variation in CYP2D6 affects endoxifen levels, and some have argued that patients who do not efficiently metabolize tamoxifen might wish to consider alternative hormonal treatments. This study evaluated an algorithm in which endoxifen levels and CYP2D6 genotypes were used to make hormonal therapy recommendations for patients on adjuvant tamoxifen for breast cancer. Patients with stage I-III breast cancer who had been taking adjuvant tamoxifen for 8-56 weeks were eligible. At enrollment, baseline whole blood and serum were sent for genotyping by Amplichip and endoxifen measurement, respectively, and endoxifen levels were also measured 3 weeks later. Results were returned to oncologists along with an algorithm-generated treatment recommendation. The algorithm recommended that participants with poor metabolizer genotype and/or baseline endoxifen level < 6 ng/mL consider alternative endocrine therapy. A medical record review evaluated actual treatment decisions. Of 99 patients on study, 18 (18 %) had findings that triggered algorithm-based recommendations to consider a change in endocrine therapy due to endoxifen < 6 ng/mL (all 18 patients) and/or poor metabolizer CYP2D6 genotype (2 of the 18). Endoxifen levels were a parts per thousand yen6 ng/mL in four of them 3 weeks later. Seven (39 % of 18) switched to a different treatment (one based on toxicity, not the algorithm). Hot flash burden was not found to be significantly associated with endoxifen < 6 ng/mL or genotype. Prospective testing of tamoxifen metabolism as gauged by CYP2D6 genotype and serum endoxifen levels is feasible. Future studies of tamoxifen metabolism and efficacy should consider including measurement of serial endoxifen levels. Although clinical evidence at present is insufficient to warrant routine CYP2D6 or endoxifen testing, some clinicians and patients did utilize this predefined algorithm to inform clinical decisions regarding optimal adjuvant endocrine therapy. C1 [Ruddy, Kathryn J.; Desantis, Stephen D.; Gelman, Rebecca S.; Punglia, Rinaa S.; Mayer, Erica L.; Tolaney, Sara M.; Winer, Eric P.; Partridge, Ann H.; Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wu, Alan H. B.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kathryn_ruddy@dfci.harvard.edu NR 21 TC 13 Z9 16 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2013 VL 141 IS 3 BP 421 EP 427 DI 10.1007/s10549-013-2700-1 PG 7 WC Oncology SC Oncology GA 239QS UT WOS:000326041100010 PM 24062210 ER PT J AU Dalby, CK Nesbitt, M Frechette, CA Kennerley, K Lacoursiere, LH Buswell, L AF Dalby, Carole K. Nesbitt, Marylou Frechette, Carol A. Kennerley, Kathleen Lacoursiere, Lisa H. Buswell, Lori TI Standardization of Initial Chemotherapy Teaching to Improve Care SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article AB Recognizing that each nurse approaches patient education differently, a team of nurses at Dana-Farber Cancer Institute satellite facilities employed quality improvement strategies to develop a standardized approach to patient education. The goal was to eliminate variation in teaching and improve patient satisfaction scores. C1 [Dalby, Carole K.; Nesbitt, Marylou] Dana Farber Canc Inst, Boston, MA 02115 USA. [Frechette, Carol A.] Milford Reg Med Ctr, DFCI, Milford, MA USA. [Kennerley, Kathleen] South Shore Hosp, DFCI, South Weymouth, MA USA. [Lacoursiere, Lisa H.] DFCI New Hampshire Oncol Hematol, Derry, Londonderry, North Ireland. [Buswell, Lori] Dana Farber Canc Inst, Nursing Serv, Boston, MA 02115 USA. [Buswell, Lori] Dana Farber Canc Inst, Clin Serv, Boston, MA 02115 USA. RP Dalby, CK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM carole_dalby@dfci.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 10 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD OCT PY 2013 VL 17 IS 5 BP 472 EP 475 DI 10.1188/13.CJON.472-475 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 237ZE UT WOS:000325909400003 PM 24080045 ER PT J AU Hunnibell, LS Slatore, CG Ballard, EA AF Hunnibell, Laura S. Slatore, Christopher G. Ballard, Ellen A. TI Foundations for Lung Nodule Management for Nurse Navigators SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID PRACTICAL ALGORITHMIC APPROACH; SMALL PULMONARY NODULES; FLEISCHNER-SOCIETY; CANCER; CT; DIAGNOSIS; GUIDELINES; STATEMENT; DESIGN; SCANS AB Lung cancer remains the most deadly cancer, with more than half of patients dying within one year of diagnosis. However, mortality rates improve with early detection. Until recently, attempts at improving early detection of lung cancer have not been shown to be beneficial, but when results from the National Lung Screening Trial showed a survivor benefit for high-risk patients who had a computed tomography scan, interest grew rapidly in creating guidelines and programs that restructure lung nodule management and screening. Oncology nurse navigators will play a crucial role in the development and administration of tracking methods, data analysis, and program development that will contribute to the multidisciplinary team in screening, tracking, and diagnosing early-stage lung cancer. C1 [Hunnibell, Laura S.] Dayton VA Med Ctr, Dayton, OH USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Ballard, Ellen A.] VA Loma Linda Healthcare Syst, Ctr Canc, Loma Linda, CA USA. RP Hunnibell, LS (reprint author), Dayton VA Med Ctr, Dayton, OH USA. EM laura@hunnibell.net OI Slatore, Christopher/0000-0003-0958-8122 NR 34 TC 8 Z9 8 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD OCT PY 2013 VL 17 IS 5 BP 525 EP 531 DI 10.1188/13.CJON.525-531 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 237ZE UT WOS:000325909400010 PM 24080051 ER PT J AU Zavin, A Arena, R Joseph, J Allsup, K Daniels, K Schulze, PC Lecker, S Forman, DE AF Zavin, Alexandra Arena, Ross Joseph, Jacob Allsup, Kelly Daniels, Karla Schulze, P. Christian Lecker, Stewart Forman, Daniel E. TI Dynamic assessment of ventilatory efficiency during recovery from peak exercise to enhance cardiopulmonary exercise testing SO EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY LA English DT Article DE Heart failure; cardiopulmonary functional testing; recovery kinetics; muscular strength ID CHRONIC HEART-FAILURE; SUBMAXIMAL EXERCISE; OXYGEN-CONSUMPTION; SKELETAL-MUSCLE; GAS-EXCHANGE; KINETICS; CARDIOMYOPATHY; ENDURANCE; CAPACITY; MARKERS AB Background: While cardiopulmonary exercise testing (CPX) assessment is generally regarded as an optimal means to assess functional capacity in heart failure (HF) patients, strength parameters are omitted. CPX indices collected in recovery may provide additional insight regarding function, including strength. Design and methods: We performed a cross-sectional controlled study. Systolic HF patients (aged >= 50 years) and age-matched controls were assessed using CPX and strength evaluations. Standard CPX indices were assessed during exercise (peak oxygen consumption [VO2], first ventilatory threshold [1stVT], and ventilatory efficiency [VE/VCO2 slope]) as well as indices at 1-minute recovery (1 min VO2, 1 min VE/VCO2, and 1 min heart rate recovery [HRR]) and differences between peak and 1-minute recovery (Delta VO2 and Delta VE/VCO2). Lower extremity strength was evaluated using the 1-repetition maximum (1RM) and power. Results: Seventy adults (31 HF; 39 controls), mean age 66.2 +/- 9.7 years were evaluated. Peak VO2 (15.4 +/- 4.2 versus 23.4 +/- 6.6 mlO(2)center dot kg(-1)center dot min(-1), p < 0.0001) and 1stVT (10.9 +/- 2.1 versus 14.4 +/- 4.0mlO(2)center dot kg(-1)center dot min(-1), p < 0.0001) were diminished in HF versus controls and VE/VCO2 slope was increased (42.3 +/- 12.2 versus 35.4 +/- 8.3, p < 0.01). HF patients had reduced 1minVO(2) (13.1 +/- 2.9 versus 16.3 +/- 3.7 mlO(2)center dot kg(-1)center dot min(-1), p < 0.0001), 1 min HRR (6.7 +/- 11.4 versus 12.4 +/- 7.6 beats, p < 0.02), and Delta VO2 (2.43 +/- 2.3 versus 7.3 +/- 5.0 mlO(2)center dot kg(-1)center dot min(-1), p < 0.0001) as well as increased 1 min VE/VCO2 (37 +/- 7.5 versus 31.5 +/- 4.4, p < 0.001) and Delta VE/VCO2 (1.17 +/- 3.0 versus -0.5 +/- 1.3, p < 0.0001). Strength parameters were relatively lower in HF. While CPX exercise parameters correlated with strength, stronger correlations were observed between CPX recovery parameters and strength. Conclusions: CPX recovery indices corroborate disease-specific aerobic differences and distinguish differences in strength. Recovery ventilatory efficiency enhances CPX's value as a comprehensive physical function tool. C1 [Zavin, Alexandra; Allsup, Kelly; Daniels, Karla; Forman, Daniel E.] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Arena, Ross; Forman, Daniel E.] Univ New Mexico, Sch Med, Phys Therapy Program, Dept Orthopaed & Rehabil, Albuquerque, NM 87131 USA. [Arena, Ross; Forman, Daniel E.] Univ New Mexico, Sch Med, Div Cardiol, Dept Internal Med, Albuquerque, NM 87131 USA. [Joseph, Jacob] VA Boston Healthcare Syst, Div Cardiovasc Med, Boston, MA USA. [Joseph, Jacob; Forman, Daniel E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Cambridge, MA 02138 USA. [Schulze, P. Christian] Columbia Univ, Med Ctr, Div Cardiol, New York, NY 10027 USA. [Lecker, Stewart] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Nephrol, Cambridge, MA 02138 USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU VA Merit Award [F4726R] FX This study was funded by a VA Merit Award (number F4726R, Ubiquitin Proteolysis and PGC-1 in Skeletal Muscle in Heart Failure). NR 32 TC 1 Z9 1 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2047-4873 EI 2047-4881 J9 EUR J PREV CARDIOL JI Eur. J. Prev. Cardiol. PD OCT PY 2013 VL 20 IS 5 BP 779 EP 785 DI 10.1177/2047487312446563 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 217TC UT WOS:000324383000009 PM 22517928 ER PT J AU Chute, CG Ullman-Cullere, M Wood, GM Lin, SM He, M Pathak, J AF Chute, Christopher G. Ullman-Cullere, Mollie Wood, Grant M. Lin, Simon M. He, Min Pathak, Jyotishman TI Some experiences and opportunities for big data in translational research SO GENETICS IN MEDICINE LA English DT Review DE clinical data representation; big data; genomics; health information technology standards ID ELECTRONIC MEDICAL-RECORDS; MOLECULAR-GENETIC TESTS; EMERGE NETWORK; GENOMIC MEDICINE; CLOUD; CONSORTIUM; DISEASE; PROJECT; PATIENT; CARE AB Health care has become increasingly information intensive. The advent of genomic data, integrated into patient care, significantly accelerates the complexity and amount of clinical data. Translational research in the present day increasingly embraces new biomedical discovery in this data-intensive world, thus entering the domain of "big data: The Electronic Medical Records and Genomics consortium has taught us many lessons, while simultaneously advances in commodity computing methods enable the academic community to affordably manage and process big data. Although great promise can emerge from the adoption of big data methods and philosophy, the heterogeneity and complexity of clinical data, in particular, pose additional challenges for big data inferencing and clinical application. However, the ultimate comparability and consistency of heterogeneous clinical information sources can be enhanced by existing and emerging data standards, which promise to bring order to clinical data chaos. Meaningful Use data standards in particular have already simplified the task of identifying clinical phenotyping patterns in electronic health records. C1 [Chute, Christopher G.; Pathak, Jyotishman] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Ullman-Cullere, Mollie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wood, Grant M.] Intermt Healthcare, Clin Genet Inst, Salt Lake City, UT USA. [Lin, Simon M.; He, Min] Marshfield Clin Fdn Med Res & Educ, Biomed Informat Res Ctr, Marshfield, WI 54449 USA. RP Chute, CG (reprint author), Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. EM Chute@mayo.edu RI Lin, Simon/L-8804-2014 FU National Human Genome Research Institute [U01-HG06379, U01-HG006389] FX We are grateful for the grant support in part from the National Human Genome Research Institute as eMERGE consortium members, specifically U01-HG06379 (Mayo Clinic) and U01-HG006389 (Marshfield Clinic). NR 49 TC 27 Z9 32 U1 4 U2 100 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD OCT PY 2013 VL 15 IS 10 BP 802 EP 809 DI 10.1038/gim.2013.121 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 234SQ UT WOS:000325665000007 PM 24008998 ER PT J AU Tarczy-Hornoch, P Amendola, L Aronson, SJ Garraway, L Gray, S Grundmeier, RW Hindorff, LA Jarvik, G Karavite, D Lebo, M Plon, SE Van Allen, E Weck, KE White, PS Yang, YP AF Tarczy-Hornoch, Peter Amendola, Laura Aronson, Samuel J. Garraway, Levi Gray, Stacy Grundmeier, Robert W. Hindorff, Lucia A. Jarvik, Gail Karavite, Dean Lebo, Matthew Plon, Sharon E. Van Allen, Eliezer Weck, Karen E. White, Peter S. Yang, Yaping TI A survey of informatics approaches to whole-exome and whole-genome clinical reporting in the electronic health record SO GENETICS IN MEDICINE LA English DT Article DE clinical decision support; clinical sequencing; decision support rules; electronic health record; electronic medical record; next-generation sequencing ID MEDICAL-RECORDS; GENETIC-VARIANTS; DECISION-SUPPORT; KNOWLEDGE; INTEGRATION AB Purpose: Genome-scale clinical sequencing is being adopted more broadly in medical practice. The National Institutes of Health developed the Clinical Sequencing Exploratory Research (CSER) program to guide implementation and dissemination of best practices for the integration of sequencing into clinical care. This study describes and compares the state of the art of incorporating whole-exome and whole-genome sequencing results into the electronic health record, including approaches to decision support across the six current CSER sites. Methods: The CSER Medical Record Working Group collaboratively developed and completed an in-depth survey to assess the communication of genome-scale data into the electronic health record. We summarized commonalities and divergent approaches. Results: Despite common sequencing platform (Illumina) adoptions, there is a great diversity of approaches to annotation tools and workflow, as well as to report generation. At all sites, reports are human-readable structured documents available as passive decision support in the electronic health record. Active decision support is in early implementation at two sites. Conclusion: The parallel efforts across CSER sites in the creation of systems for report generation and integration of reports into the electronic health record, as well as the lack of standardized approaches to interfacing with variant databases to create active clinical decision support, create opportunities for cross-site and vendor collaborations. C1 [Tarczy-Hornoch, Peter; Amendola, Laura; Aronson, Samuel J.; Garraway, Levi; Grundmeier, Robert W.; Hindorff, Lucia A.; Karavite, Dean; Plon, Sharon E.; Van Allen, Eliezer; Weck, Karen E.; White, Peter S.] NHGRI, NIH, Clin Sequencing Exploratory Res Elect Med Records, Bethesda, MD 20892 USA. [Tarczy-Hornoch, Peter; Amendola, Laura; Jarvik, Gail] Univ Washington, Seattle, WA 98195 USA. [Aronson, Samuel J.; Lebo, Matthew] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA. [Garraway, Levi; Gray, Stacy; Van Allen, Eliezer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Garraway, Levi; Gray, Stacy; Grundmeier, Robert W.; Lebo, Matthew; White, Peter S.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, Stacy; Van Allen, Eliezer] Broad Inst MIT & Harvard, Cambridge, MA USA. [Grundmeier, Robert W.; Karavite, Dean; White, Peter S.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Hindorff, Lucia A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Lebo, Matthew] Brigham & Womens Hosp, Boston, MA 02115 USA. [Plon, Sharon E.; Yang, Yaping] Baylor Coll Med, Houston, TX 77030 USA. [Weck, Karen E.] Univ N Carolina, Chapel Hill, NC USA. RP Tarczy-Hornoch, P (reprint author), NHGRI, NIH, Clin Sequencing Exploratory Res Elect Med Records, Bethesda, MD 20892 USA. EM pth@uw.edu RI Jarvik, Gail/N-6476-2014; OI Jarvik, Gail/0000-0002-6710-8708; Weck, Karen/0000-0002-8516-333X; Van Allen, Eliezer/0000-0002-0201-4444; Tarczy-Hornoch, Peter/0000-0003-1047-179X; Lebo, Matthew/0000-0002-9733-5207 FU National Institutes of Health [U01HG006507, U01HG00637, U01HG006500, U01HG606492, U01HG006487, U01HG006485, U01HG006546, KG100355, RC1LM010526, UL1RR02574, UL1TR000423, U01HL098188, 275200800001C-2-0-1]; Susan G. Komen foundation; Washington State Life Sciences Discovery Fund; Northwest Institute for Genetic Medicine; Dana-Farber Cancer Institute Leadership Council FX All the authors contributed equally to the writing of the this article. The authors thank the members of the Clinical Sequencing Exploratory Research (CSER) consortium, in particular all additional members of the informatics teams at each of the six current CSER sites. The following sources of funding supported parts of the work described in this article: National Institutes of Health extramural projects U01HG006507, U01HG00637, U01HG006500, U01HG606492, U01HG006487, U01HG006485, U01HG006546, KG100355, RC1LM010526, UL1RR02574, UL1TR000423, U01HL098188, and 275200800001C-2-0-1; the Susan G. Komen foundation; the Washington State Life Sciences Discovery Fund; the Northwest Institute for Genetic Medicine; and the Dana-Farber Cancer Institute Leadership Council. L.A.H. is a member of the National Human Genome Research Institute CSER staff team, responsible for scientific program management of the CSER program. NR 25 TC 22 Z9 22 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD OCT PY 2013 VL 15 IS 10 BP 824 EP 832 DI 10.1038/gim.2013.120 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 234SQ UT WOS:000325665000010 PM 24071794 ER PT J AU Rauh-Hain, JA Diver, EJ Clemmer, JT Bradford, LS Clark, RM Growdon, WB Goodman, AK Boruta, DM Schorge, JO del Carmen, MG AF Rauh-Hain, J. Alejandro Diver, Elisabeth J. Clemmer, Joel T. Bradford, Leslie S. Clark, Rachel M. Growdon, Whitfield B. Goodman, A. K. Boruta, David M., II Schorge, John O. del Carmen, Marcela G. TI Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian carcinosarcoma; High grade papillary serous ovarian cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; MIXED MESODERMAL TUMORS; RACIAL DISPARITIES; MULLERIAN TUMORS; CORPUS UTERI; CANCER; CHEMOTHERAPY; SURVIVAL; PLATINUM; STAGE AB Objective. The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated ctinico-pathologic factors. Methods. The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazard model. Results. The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P < 0.001). This difference persisted for each FIGO disease stages I-IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival. Conclusions. OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Diver, Elisabeth J.; Clemmer, Joel T.; Bradford, Leslie S.; Clark, Rachel M.; Growdon, Whitfield B.; Goodman, A. K.; Boruta, David M., II; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 23 TC 12 Z9 12 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2013 VL 131 IS 1 BP 46 EP 51 DI 10.1016/j.ygyno.2013.07.097 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 237BF UT WOS:000325842500011 PM 23906658 ER PT J AU Norquist, B Harrell, M Walsh, T Lee, MK King, MC Swisher, EM Birrer, MJ AF Norquist, B. Harrell, M. Walsh, T. Lee, M. K. King, M. C. Swisher, E. M. Birrer, M. J. TI Germline mutations in dna repair genes in women with ovarian, peritoneal, or fallopian tube cancer treated on COG protocol 218 SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Norquist, B.; Swisher, E. M.] Univ Washington, Div Gynecol Oncol, Seattle, WA 98195 USA. [Harrell, M.; Walsh, T.; Lee, M. K.; King, M. C.; Swisher, E. M.] Univ Washington, Div Med Genet, Seattle, WA 98195 USA. [Birrer, M. J.] Mass Gen Hosp, Div Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2013 VL 131 IS 1 BP 259 EP 259 DI 10.1016/j.ygyno.2013.07.032 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 237BF UT WOS:000325842500078 ER PT J AU Kawamoto, T Sasajima, J Sugiyama, Y Nakamura, K Tanabe, H Fujiya, M Nata, T Iuchi, Y Ashida, T Torimoto, Y Mizukami, Y Kohgo, Y AF Kawamoto, Toru Sasajima, Junpei Sugiyama, Yoshiaki Nakamura, Kazumasa Tanabe, Hiroki Fujiya, Mikihiro Nata, Toshie Iuchi, Yasuyuki Ashida, Toshifumi Torimoto, Yoshihiro Mizukami, Yusuke Kohgo, Yutaka TI Ex vivo activation of angiogenic property in human peripheral blood-derived monocytes by thrombopoietin SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Thrombopoietin; Ex vivo culture; CD11b(+) monocytes; Spheroid; Angiogenesis ID ENDOTHELIAL PROGENITOR CELLS; HEMATOPOIETIC STEM-CELLS; BONE-MARROW-CELLS; SERUM-FREE MEDIUM; PLATELET PRODUCTION; REFRACTORY ANGINA; LIMB ISCHEMIA; TRANSPLANTATION; EXPANSION; GROWTH AB Human peripheral blood mononuclear cells (PB-MNCs) have angiogenic properties, which make them promising cells for use in angiogenic therapy approaches in regenerative medicine. To explore an efficient method for expanding pro-angiogenic cells from PB-MNCs, we developed a novel serum-free culture system composed of X-VIVO15 medium supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and thrombopoietin (TPO). Using this ex vivo culture, we obtained floating spheres composed mainly of CD11b(+) monocytes expressing c-Mpl (TPO receptor) and which exhibited acetylated low-density lipoprotein uptake and phagocytosis. Expression of IL-8, CXCR4, and vasohibin-2 mRNA was upregulated in these cells. In the presence of TPO, the number and size of the spheres were increased. In a nude mouse hind-limb ischemia model, the intramuscular injection of spheroid cells treated with TPO rescued blood perfusion more effectively than that without TPO. These results indicate that the ex vivo addition of TPO augments the pro-angiogenic activity of peripheral CD11b(+) monocytes, suggesting that this method shows promise for uses in human cell therapy aimed at the induction of vascular regeneration by activating the angiogenic properties of human peripheral blood-derived monocytes. C1 [Kawamoto, Toru; Sasajima, Junpei; Sugiyama, Yoshiaki; Nakamura, Kazumasa; Tanabe, Hiroki; Fujiya, Mikihiro; Ashida, Toshifumi; Torimoto, Yoshihiro; Mizukami, Yusuke; Kohgo, Yutaka] Asahikawa Med Univ, Dept Med, Div Gastroenterol & Hematol Oncol, Asahikawa, Hokkaido 0788510, Japan. [Nata, Toshie; Iuchi, Yasuyuki; Ashida, Toshifumi; Mizukami, Yusuke] Sapporo Higashi Tokusyukai Hosp, Clin Res Ctr, Sapporo, Hokkaido, Japan. [Torimoto, Yoshihiro] Asahikawa Med Univ Hosp, Ctr Oncol, Asahikawa, Hokkaido 0788510, Japan. [Mizukami, Yusuke] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 20114 USA. [Mizukami, Yusuke] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kohgo, Y (reprint author), Asahikawa Med Univ, Dept Med, Div Gastroenterol & Hematol Oncol, 2Jo,1Chome, Asahikawa, Hokkaido 0788510, Japan. EM yk1950@asahikawa-med.ac.jp FU New Energy and Industrial Technology Development Organization of Japan [07A05010a]; Ministry of Education, Science, Sports, and Culture of Japan [22590754] FX This study was supported by research funding to Y.M. from the New Energy and Industrial Technology Development Organization of Japan (07A05010a) and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (22590754). NR 55 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0925-5710 EI 1865-3774 J9 INT J HEMATOL JI Int. J. Hematol. PD OCT PY 2013 VL 98 IS 4 BP 417 EP 429 DI 10.1007/s12185-013-1423-8 PG 13 WC Hematology SC Hematology GA 238KK UT WOS:000325945000006 PM 24002641 ER PT J AU Burke, RE Ryan, P AF Burke, Robert E. Ryan, Patrick TI Postdischarge Clinics: Hospitalist Attitudes and Experiences SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID FOLLOW-UP; CARE; DISCHARGE; TRANSITIONS; CONTINUITY; PHYSICIANS AB Novel methods for improving transitions of care are needed. Hospitalist-run postdischarge clinics (PDCs) may improve access to postdischarge care, but require practice change from providers. We conducted a Web-based cross-sectional survey of hospitalists at 37 academic medical centers across the United States and a large private employer of hospitalists to assess the attitudes of hospitalists toward postdischarge care and PDCs. Two hundred twenty-eight of 814 hospitalists responded to the survey (28%). Responding hospitalists commonly (55%) experienced difficulty arranging outpatient follow-up, and felt that lack of access was responsible for most patient problems after discharge (61%). Despite this, 62% felt hospitalists should not provide postdischarge care in a clinic, and 77% felt they would require extra compensation for work in a PDC. However, 74% thought such a clinic would decrease emergency department visits. Practicing in a PDC was associated with a trend toward positive attitudes about providing postdischarge care (P = 0.054). Responding hospitalists expressed difficulty arranging appropriate postdischarge care, confidence that PDCs would reduce postdischarge utilization, and reservations about working in a PDC, perhaps because of practical or financial concerns. These results are important given the current emphasis on reducing hospital readmissions. Further work evaluating the experience of hospitalists in PDCs is needed. Journal of Hospital Medicine 2013;8:578-581. (c) 2013 Society of Hospital Medicine C1 [Burke, Robert E.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Hosp Med Sect, Denver, CO USA. [Burke, Robert E.; Ryan, Patrick] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. RP Burke, RE (reprint author), Denver VA Med Ctr, Mailstop 111,1055 Clermont St, Denver, CO 80220 USA. EM Robert.Burke5@va.gov FU Colorado Research Enhancement Award Program FX Dr. Burke had full access to all of the data in the study and takes 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 represent the views of the Department of Veterans Affairs. Dr. Burke was supported by grant funding from the Colorado Research Enhancement Award Program to Improve Care Coordination for Veterans. Dr. Ryan has no conflicts of interest to disclose. NR 14 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2013 VL 8 IS 10 BP 578 EP 581 DI 10.1002/jhm.2085 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 230NF UT WOS:000325347000007 PM 24101543 ER PT J AU Adams, JM Evans, M AF Adams, Jeffrey M. Evans, Michael TI Influencing the Nursing Commitment to Workforce Satisfaction and the Origins of Magnet SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB This department highlights nursing leaders who have demonstrated a commitment to patient care leadership. This interview profiles Michael Evans, PhD, RN, FAAN, dean of the Texas Tech University School of Nursing and president of the American Nurses Credentialing Center. C1 [Adams, Jeffrey M.] Ctr Innovat Care Delivery, Boston, MA USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, Michael] Texas Tech Univ, Sch Nursing, Lubbock, TX 79409 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM jadams9@partners.org NR 3 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD OCT PY 2013 VL 43 IS 10 BP 491 EP 494 DI 10.1097/NNA.0b013e3182a3e7cd PG 4 WC Nursing SC Nursing GA 229NA UT WOS:000325271900002 ER PT J AU Ersek, M Carpenter, JG AF Ersek, Mary Carpenter, Joan G. TI Geriatric Palliative Care in Long-Term Care Settings with a Focus on Nursing Homes SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; SUSTAINING TREATMENT PROGRAM; QUALITY-IMPROVEMENT PROJECT; PAIN MANAGEMENT-PRACTICES; ADVANCED DEMENTIA; HOSPICE ENROLLMENT; PHYSICIAN ORDERS; REDUCE HOSPITALIZATIONS; IMPLEMENTATION SCIENCE AB Almost 1.7 million older Americans live in nursing homes, representing a large proportion of the frailest, most vulnerable elders needing long-term care. In the future, increasing numbers of older adults are expected to spend time and to die in nursing homes. Thus, understanding and addressing the palliative care needs of this population are critical. The goals of this paper are to describe briefly the current state of knowledge about palliative care needs, processes, and outcomes for nursing home residents; identify gaps in this knowledge; and propose priorities for future research in this area. C1 [Ersek, Mary] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Carpenter, Joan G.] Univ Utah, Coll Nursing, Hartford Ctr Geriatr Nursing Excellence, Salt Lake City, UT 84112 USA. [Carpenter, Joan G.] Coastal Hosp & Palliat Care, Salisbury, MD USA. RP Ersek, M (reprint author), Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave Annex, Philadelphia, PA 19104 USA. EM ersekm@nursing.upenn.edu FU John A. Hartford Foundation's National Hartford Centers of Gerontological Nursing Excellence Award Program FX Ms. Carpenter is a 2011-2013 Patricia G. Archbold Scholar supported by the John A. Hartford Foundation's National Hartford Centers of Gerontological Nursing Excellence Award Program. NR 110 TC 6 Z9 6 U1 5 U2 22 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT 1 PY 2013 VL 16 IS 10 BP 1180 EP 1187 DI 10.1089/jpm.2013.9474 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 229LI UT WOS:000325265800009 PM 23984636 ER PT J AU Loggers, ET Maciejewski, PK Jimenez, R Nilsson, M Paulk, E Stieglitz, H Prigerson, HG AF Loggers, Elizabeth T. Maciejewski, Paul K. Jimenez, Rachel Nilsson, Matthew Paulk, Elizabeth Stieglitz, Heather Prigerson, Holly G. TI Predictors of Intensive End-of-Life and Hospice Care in Latino and White Advanced Cancer Patients SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID KARNOFSKY PERFORMANCE STATUS; ETHNIC-DIFFERENCES; DEATH; DIRECTIVES; ATTITUDES; RELIABILITY; DECISIONS; VALIDITY; PLACE AB Background: The role of end-of-life (EOL) care preferences and conversations in receipt of care near death for Latinos is unclear.Objective: This study examines rates and predictors of intensive EOL and hospice care among Latino and white advanced cancer patients. Design: Two-hundred-and-ninety-two self-reported Latino (n=58) and white (n=234) Stage IV cancer patients participated in a U.S. multisite, prospective, cohort study from September 2002 to August 2008. The Latino and white, non-Hispanic participants were interviewed and followed until death, a median of 118.5 days from baseline. Measurements: Patient-reported, baseline predictors of EOL care included EOL care preference; terminal illness acknowledgement; EOL discussion; completion of a DNR order; and religious coping. Caregiver postmortem interviews provided information regarding EOL care received. Intensive EOL care was defined as resuscitation and/or ventilation followed by death in an intensive care unit. Hospice was either in- or outpatient. Results: Latino and white patients received intensive EOL and hospice care at similar rates (5.2% and 3.4% for intensive care, p=0.88; 70.7% versus 73.4% for hospice, p=0.33). No white or Latino patient who reported a DNR order or EOL discussion at baseline received intensive EOL care. Religious coping and a preference for life-extending care predicted intensive EOL care for white patients (adjusted odds ratio [aOR] 6.69 [p=0.02] and aOR 6.63 [p=0.01], respectively), but not for Latinos. No predictors were associated with Latino hospice care. Conclusions: EOL discussions and DNR orders may prevent intensive EOL care among Latino cancer patients. Efforts should continue to engage Latino patients and caregivers in these activities. C1 [Loggers, Elizabeth T.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Loggers, Elizabeth T.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Loggers, Elizabeth T.] Seattle Canc Care Alliance, Seattle, WA USA. [Maciejewski, Paul K.; Nilsson, Matthew; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. [Maciejewski, Paul K.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Jimenez, Rachel] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Paulk, Elizabeth; Stieglitz, Heather] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. RP Loggers, ET (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM loggers.e@ghc.org FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370]; Dana-Farber/Harvard Cancer Center [U56CA118641, P30CA0651]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute; American Society of Clinical Oncology FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA 106370 from the National Cancer Institute; Dana-Farber/Harvard Cancer Center U56CA118641 and P30CA0651 pilot grants and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute; and a 2009 American Society of Clinical Oncology Young Investigator Award to Dr. Loggers. NR 34 TC 5 Z9 5 U1 3 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT 1 PY 2013 VL 16 IS 10 BP 1249 EP 1254 DI 10.1089/jpm.2013.0164 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 229LI UT WOS:000325265800020 PM 24053593 ER PT J AU Greenawalt, DS Copeland, LA MacCarthy, AA Sun, FFF Zeber, JE AF Greenawalt, David Sloan Copeland, Laurel Anne MacCarthy, Andrea A. Sun, Fangfang F. Zeber, John Edward TI Posttraumatic stress disorder and odds of major invasive procedures among US Veterans Affairs patients SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Posttraumatic stress disorder; Depression; Veterans; Invasive procedures; Surgery ID CORONARY-HEART-DISEASE; ADMINISTRATIVE DATA; HEALTH-CARE; MENTAL-DISORDERS; MEDICAL-CARE; DISPARITIES; DEPRESSION; MORTALITY; PTSD; ASSOCIATION AB Objectives: Although individuals with posttraumatic stress disorder (PTSD) are at heightened risk for several serious health conditions, research has not examined how having PTSD impacts receipt of invasive procedures that may alleviate these problems. We examined whether PTSD, after controlling for major depression, was associated with odds of receiving common types of major invasive procedures, and whether race, ethnicity, and gender was associated with odds of procedures. Methods: Veterans Health Administration patients with PTSD and/or depression were age-matched with patients without these disorders. The odds of invasive hip/knee, digestive system, coronary artery bypass graft/percutaneous coronary intervention (CABG/PCI), and vascular procedures during FY2006-2009 were modeled for the full sample of 501,489 patients and for at-risk subsamples with medical conditions alleviated by the procedures examined. Results: Adjusting for demographic covariates and medical comorbidity, PTSD without depression was associated with decreased odds of all types of procedures (odds ratios [OR] range 0.74-0.82), as was depression without PTSD (OR range 0.59-0.77). In analyses of at-risk patients, those with PTSD only were less likely to undergo hip/knee (OR = 0.78) and vascular procedures (OR = 0.73) but not CABG/PCI. African-Americans and women at-risk patients were less likely to undergo hip/knee, vascular, and CABG/PCI procedures (OR range 031-0.82). Conclusion: With the exception of CABG/PCI among at-risk patients, Veterans with PTSD and/or depression were less likely to undergo all types of procedures examined. Future studies should examine the reasons for this disparity and whether it is associated with subsequent adverse outcomes. Published by Elsevier Inc. C1 [Greenawalt, David Sloan] VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX 76711 USA. [Copeland, Laurel Anne; Sun, Fangfang F.; Zeber, John Edward] Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Dept Vet Affairs, Temple, TX 76504 USA. [Copeland, Laurel Anne; Sun, Fangfang F.; Zeber, John Edward] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX 76502 USA. [MacCarthy, Andrea A.] South Texas Vet Hlth Care Syst, Ctr Improving Vet Hlth Res, San Antonio, TX 78229 USA. RP Greenawalt, DS (reprint author), Albany Stratton VA Med Ctr, 113 Holland Ave 151, Albany, NY 12208 USA. EM mycapemaypoint@yahoo.com OI Copeland, Laurel/0000-0002-9478-0209 FU Veterans Health Administration, Health Services Research and Development [IIR-09-335]; Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment VISN 17 Center of Excellence for Research on Returning War Veterans; Central Texas Veterans Health Care System (CTVHCS); Center for Applied Health Research; CTVHCS; Scott & White Healthcare, Temple, TX FX This study was funded by a grant from the Veterans Health Administration, Health Services Research and Development #IIR-09-335 (PI: Laurel A. Copeland). Preparation of this manuscript was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment VISN 17 Center of Excellence for Research on Returning War Veterans, Central Texas Veterans Health Care System (CTVHCS), and the Center for Applied Health Research, a research center jointly sponsored by CTVHCS and Scott & White Healthcare, Temple, TX. NR 57 TC 2 Z9 3 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD OCT PY 2013 VL 75 IS 4 BP 386 EP 393 DI 10.1016/j.jpsychores.2013.08.012 PG 8 WC Psychiatry SC Psychiatry GA 236ZQ UT WOS:000325838400016 PM 24119948 ER PT J AU Greer, DM Scripko, PD Wu, O Edlow, BL Bartscher, J Sims, JR Camargo, EEC Singhal, AB Furie, KL AF Greer, David M. Scripko, Patricia D. Wu, Ona Edlow, Brian L. Bartscher, James Sims, Jonathan R. Camargo, Erica E. C. Singhal, Aneesh B. Furie, Karen L. TI Hippocampal Magnetic Resonance Imaging Abnormalities in Cardiac Arrest are Associated with Poor Outcome SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Cardiac arrest; coma; magnetic resonance imaging; prognosis ID TRANSIENT GLOBAL AMNESIA; CEREBRAL-ISCHEMIA; RAT HIPPOCAMPUS; BRAIN-DAMAGE; DIFFUSION; CA1; NEURONS; MRI AB Background: The role of neuroimaging in assessing prognosis in comatose cardiac survivors appears promising, but little is known regarding the import of particular spatial patterns. We report a specific spatial imaging abnormality on magnetic resonance imaging (MRI) that portends a poor prognosis: bilateral hippocampal hyperintensities on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. Methods: Eighty sequential comatose cardiac arrest patients underwent MRI scans. Qualitative and quantitative regional analyses were performed. Patients were categorized as HIPPO+ (n = 18) or HIPPO- (n = 62) based on whether they had bilateral hippocampal hyperintensities. Poor outcome was defined by a modified Rankin Scale (mRS) score >= 4 at 6 months. Results: Patients with bilateral hippocampal abnormalities had a higher frequency of poor outcome (P = .032). HIPPO+ patients suffered more severe cerebral injury, with lower whole brain apparent diffusion coefficient values (P = .043) and a greater number of affected regions on DWI (P = .001) and FLAIR (P = .001) than HIPPO- patients. The hippocampal approach was 100% specific for a poor prognosis; only 1 patient survived and remained in a vegetative state. Conclusions: Bilateral hippocampal hyperintensities on MRI may be a specific imaging finding that is indicative of poor prognosis in patients who suffer global hypoxic-ischemic injury. More research on the prognostic significance of this and similar neuroimaging patterns is indicated. C1 [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06530 USA. [Greer, David M.; Scripko, Patricia D.; Edlow, Brian L.; Sims, Jonathan R.; Camargo, Erica E. C.; Singhal, Aneesh B.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bartscher, James] Henry Ford Hosp, Detroit, MI 48202 USA. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Greer, DM (reprint author), Yale Univ, Sch Med, Dept Neurol, 15 York St, New Haven, CT 06530 USA. EM david.greer@yale.edu NR 24 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD OCT PY 2013 VL 22 IS 7 BP 899 EP 905 DI 10.1016/j.jstrokecerebrovasdis.2012.08.006 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 237MK UT WOS:000325874200042 PM 22995378 ER PT J AU Ellis, C Knapp, RG Gilbert, GE Egede, LE AF Ellis, Charles Knapp, Rebecca G. Gilbert, Gregory E. Egede, Leonard E. TI Factors Associated with Delays in Seeking Treatment for Stroke Care in Veterans SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; delays seeking treatment; veterans ID SEVERITY; LITERACY; HEALTH; DISPARITIES AB Background: Our objective was to examine the association between delay in seeking treatment (DST) for stroke care and demographic and clinical characteristics variables in a sample of veterans. Methods: We used survey data from 100 veterans with a diagnosis of stroke who were receiving poststroke care at a Veterans Affairs (VA) Medical Center in the southeastern United States to evaluate the relationship between DST and key sample demographic and clinical characteristics. We used backward stepwise logistic regression models to assess the independent association between DSTand demographic and clinical variables. Results: We found that stroke survivors reporting DST were more likely to be black (56.4% versus 32.8%; P = .02) and younger at the time of stroke onset (58.1 years versus 63.7 years; P = .02). In backward stepwise logistic regression models, being black was an independent predictor of DST (odds ratio [OR] 2.76; 95% confidence interval [CI], 1.04-7.30; P = .04) in this veteran population. Conclusions: Race appears to be a key factor associated with an increased likelihood of delays in seeking urgent stroke care in veterans. Future studies need to further examine the complex sociodemographic profile of patients who are most likely to delay seeking care for stroke and to develop interventions to reduce the impact of DST. C1 [Ellis, Charles; Knapp, Rebecca G.; Gilbert, Gregory E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, VA Ctr Dis Prevent & Hlth Intervent Diverse Popul, Charleston, SC USA. [Ellis, Charles] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Knapp, Rebecca G.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. RP Ellis, C (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM ellisc@musc.edu RI Gilbert, Gregory/C-7735-2016 OI Gilbert, Gregory/0000-0003-0879-5496 FU Veterans Health Administration Health Services Research and Development program (CDA) [07-012-3] FX Dr Ellis was supported by a career development award (CDA# 07-012-3) from the Veterans Health Administration Health Services Research and Development program for this project. NR 18 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD OCT PY 2013 VL 22 IS 7 BP E136 EP E141 DI 10.1016/j.jstrokecerebrovasdis.2012.09.017 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 237MK UT WOS:000325874200021 PM 23219014 ER PT J AU Olson, DM Cox, M Pan, WQ Sacco, RL Fonarow, GC Zorowitz, R LaBresh, KA Schwamm, LH Williams, L Goldstein, LB Bushnell, CD Peterson, ED AF Olson, DaiWai M. Cox, Margueritte Pan, Wenqin Sacco, Ralph L. Fonarow, Gregg C. Zorowitz, Richard LaBresh, Kenneth A. Schwamm, Lee H. Williams, Linda Goldstein, Larry B. Bushnell, Cheryl D. Peterson, Eric D. CA Adherence Evaluation Acute Ischemi TI Death and Rehospitalization after Transient Ischemic Attack or Acute Ischemic Stroke: One-year Outcomes from the Adherence Evaluation of Acute Ischemic Stroke-Longitudinal Registry SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Acute stroke; stroke care; stroke management; transient ischemic attack ID HEALTH-CARE PROFESSIONALS; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; OF-NEUROLOGY-AFFIRMS; SELF-REPORT; CARDIOVASCULAR RADIOLOGY; MEDICARE BENEFICIARIES; MYOCARDIAL-INFARCTION; GUIDELINES-STROKE; MINOR STROKE AB Background: Longitudinal data directly comparing the rates of death and rehospitalization of patients discharged after transient ischemic attack (TIA) versus acute ischemic stroke (AIS) are lacking. Methods: Data were analyzed from 2802 patients (TIA n = 552; AIS n = 2250) admitted to 100 U. S. hospitals participating in the Get With The Guidelines-Stroke and the Adherence Evaluation of Acute Ischemic Stroke-Longitudinal registry. The primary composite outcome was the adjusted rate of all-cause death and rehospitalization over 1 year after discharge. Four additional single or combined outcomes were explored. Results: Compared with AIS, TIA patients were older (median 69 v 66 years; P = .007) and more likely female (53.3% v 44.2%; P < .0001). Secondary prevention medication use after hospital discharge was less intensive after TIA, with underuse for both conditions. All-cause death or rehospitalization at 1 year was similar for TIA and AIS patients (37.7% v 34.6%; P = .271); the frequency for TIA patients was higher after covariate adjustment (hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.01-1.41). One-year all-cause mortality was similar among those with TIA compared to AIS patients (3.8% v 5.7%; P = .071; adjusted HR 0.86; 95% CI 0.52-1.42). All-cause rehospitalizations were higher for TIA compared to AIS patients (36.4% v 33.0%; P = .186; adjusted HR 1.20; 95% CI 1.02-1.42), but similar for stroke rehospitalizations (10.1% v 7.4%; P = .037; adjusted HR 1.38, 95% CI 0.997-1.92). Conclusions: Patients with TIA have similar or worse 12-month postdischarge risk of death or rehospitalization as compared with those with AIS. Outcomes after TIA and AIS might be improved with better adherence to secondary preventive guidelines. C1 [Olson, DaiWai M.; Cox, Margueritte; Pan, Wenqin; Goldstein, Larry B.; Peterson, Eric D.] Duke Clin Res Inst, Dept Med, Durham, NC USA. [Sacco, Ralph L.; Peterson, Eric D.] Univ Miami, Dept Neurol, Miami, FL USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Zorowitz, Richard] Johns Hopkins Bayview Med Ctr, Dept Phys Med & Rehabil, Baltimore, MD USA. [LaBresh, Kenneth A.] Res Triangle Int, Healthcare Qual & Outcomes Program, Res Triangle Pk, NC USA. [Schwamm, Lee H.] Harvard Univ, Dept Neurol, Boston, MA 02115 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Williams, Linda] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Williams, Linda] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. [Bushnell, Cheryl D.] Wake Forest Univ Hlth Sci, Dept Neurol, Winston Salem, NC USA. RP Olson, DM (reprint author), Duke Univ, Dept Med, Div Neurol, Box 2900, Durham, NC 27710 USA. EM DaiWai.Olson@UTSouthwestern.edu RI LaBresh, Kenneth/A-6995-2017; OI LaBresh, Kenneth/0000-0001-9040-1956; Schwamm, Lee/0000-0003-0592-9145 FU Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; Agency for Healthcare Research and Quality [U18HS016964] FX The study was conceived and designed by the AVAIL team, researchers at the Duke Clinical Research Institute (DCRI), the project Executive Committee and an AHA representative. This research project was supported by unrestricted funds from Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and conducted through collaboration with the GWTG-Stroke program. AVAIL analyses were supported in part by the Agency for Healthcare Research and Quality (U18HS016964). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ. NR 41 TC 4 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD OCT PY 2013 VL 22 IS 7 BP E181 EP E188 DI 10.1016/j.jstrokecerebrovasdis.2012.11.001 PG 8 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 237MK UT WOS:000325874200028 PM 23273788 ER PT J AU Morgan, RJ Alvarez, RD Armstrong, DK Burger, RA Chen, LM Copeland, L Crispens, MA Gershenson, DM Gray, HJ Hakam, A Havrilesky, LJ Johnston, C Lele, S Martin, L Matulonis, UA O'Malley, DM Penson, RT Powell, MA Remmenga, SW Sabbatini, P Santoso, JT Schink, JC Teng, N Werner, TL Dwyer, MA Hughes, M AF Morgan, Robert J., Jr. Alvarez, Ronald D. Armstrong, Deborah K. Burger, Robert A. Chen, Lee-may Copeland, Larry Crispens, Marta Ann Gershenson, David M. Gray, Heidi J. Hakam, Ardeshir Havrilesky, Laura J. Johnston, Carolyn Lele, Shashikant Martin, Lainie Matulonis, Ursula A. O'Malley, David M. Penson, Richard T. Powell, Matthew A. Remmenga, Steven W. Sabbatini, Paul Santoso, Joseph T. Schink, Julian C. Teng, Nelson Werner, Theresa L. Dwyer, Mary A. Hughes, Miranda TI Ovarian Cancer, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; PRIMARY PERITONEAL CANCER; STAGE-III OVARIAN; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; RECURRENT EPITHELIAL OVARIAN; FALLOPIAN-TUBE CANCER; QUALITY-OF-LIFE; INTRAPERITONEAL CHEMOTHERAPY; PHASE-II; INTRAVENOUS PACLITAXEL AB These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made. C1 [Morgan, Robert J., Jr.] City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA. [Alvarez, Ronald D.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Armstrong, Deborah K.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Burger, Robert A.; Martin, Lainie] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chen, Lee-may] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Copeland, Larry; O'Malley, David M.] Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Copeland, Larry; O'Malley, David M.] Solove Res Inst, Columbus, OH 43210 USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gray, Heidi J.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Hakam, Ardeshir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Havrilesky, Laura J.] Duke Canc Inst, Durham, NC 27710 USA. [Johnston, Carolyn] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lele, Shashikant] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Matulonis, Ursula A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Penson, Richard T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Powell, Matthew A.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Powell, Matthew A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Remmenga, Steven W.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Sabbatini, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Santoso, Joseph T.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Schink, Julian C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Teng, Nelson] Stanford Canc Inst, Stanford, CA USA. [Werner, Theresa L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Dwyer, Mary A.; Hughes, Miranda] Natl Comprehens Canc Network, Salt Lake City, UT USA. RP Morgan, RJ (reprint author), City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA. RI OMalley, David/E-3789-2011 NR 68 TC 43 Z9 43 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2013 VL 11 IS 10 BP 1199 EP 1209 PG 11 WC Oncology SC Oncology GA 238FX UT WOS:000325929600004 PM 24142821 ER PT J AU Crawford, J Armitage, J Balducci, L Becker, PS Blayney, DW Cataland, SR Heaney, ML Hudock, S Kloth, DD Kuter, DJ Lyman, GH McMahon, B Rugo, HS Saad, AA Schwartzberg, LS Shayani, S Steensma, DP Talbott, M Vadhan-Raj, S Westervelt, P Westmoreland, M Dwyer, M Ho, M AF Crawford, Jeffrey Armitage, James Balducci, Lodovico Becker, Pamela Sue Blayney, Douglas W. Cataland, Spero R. Heaney, Mark L. Hudock, Susan Kloth, Dwight D. Kuter, David J. Lyman, Gary H. McMahon, Brandon Rugo, Hope S. Saad, Ayman A. Schwartzberg, Lee S. Shayani, Sepideh Steensma, David P. Talbott, Mahsa Vadhan-Raj, Saroj Westervelt, Peter Westmoreland, Michael Dwyer, Mary Ho, Maria TI Myeloid Growth Factors SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMA; STEM-CELL TRANSPLANTATION; CHEMOTHERAPY-INDUCED NEUTROPENIA; PATIENTS RECEIVING CHEMOTHERAPY; INDUCED FEBRILE NEUTROPENIA; CONTROLLED PHASE-III; HIGH-DOSE CHEMOTHERAPY; BIOSIMILAR G-CSF; PERIPHERAL-BLOOD AB Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting C1 [Crawford, Jeffrey] Duke Canc Inst, Durham, NC 27710 USA. [Armitage, James] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Balducci, Lodovico] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Becker, Pamela Sue] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Blayney, Douglas W.] Stanford Canc Inst, Stanford, CA USA. [Cataland, Spero R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Cataland, Spero R.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Heaney, Mark L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hudock, Susan] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA. [Kloth, Dwight D.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Kuter, David J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [McMahon, Brandon] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Rugo, Hope S.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Saad, Ayman A.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Schwartzberg, Lee S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Shayani, Sepideh] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA USA. [Steensma, David P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Talbott, Mahsa] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Vadhan-Raj, Saroj] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Westervelt, Peter] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Westmoreland, Michael] Washington Univ, Sch Med, St Louis, MO USA. RP Crawford, J (reprint author), Duke Canc Inst, Durham, NC 27710 USA. OI Kloth, Dwight/0000-0001-7220-2830; Steensma, David/0000-0001-5130-9284; Saad, Ayman /0000-0003-0003-0130 NR 108 TC 23 Z9 25 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2013 VL 11 IS 10 BP 1266 EP 1290 PG 25 WC Oncology SC Oncology GA 238FX UT WOS:000325929600010 PM 24142827 ER PT J AU Dinkel, J Khalilzadeh, O Hintze, C Fabel, M Puderbach, M Eichinger, M Schlemmer, HP Thorn, M Heussel, CP Thomas, M Kauczor, HU Biederer, J AF Dinkel, J. Khalilzadeh, O. Hintze, C. Fabel, M. Puderbach, M. Eichinger, M. Schlemmer, H. -P. Thorn, M. Heussel, C. P. Thomas, M. Kauczor, H. -U. Biederer, J. TI Inter-observer reproducibility of semi-automatic tumor diameter measurement and volumetric analysis in patients with lung cancer SO LUNG CANCER LA English DT Article DE Lung cancer; Volumetric analysis; Inter-rater reliability; Tumor size; WHO guideline; RECIST guideline ID SOLID TUMORS; PULMONARY NODULES; RESPONSE EVALUATION; RECIST CRITERIA; THORACIC CT; VARIABILITY; LESIONS; ACCURACY; METASTASES; TRIALS AB Objectives: Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. Methods: CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. Results: Manual measurements of the tumor longest diameter were significantly (p < 0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p < 0.001) and area (0.995 vs. 0.988; p = 0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2-3 times that of semi-automated measurement. Conclusions: By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Dinkel, J.; Kauczor, H. -U.; Biederer, J.] Univ Heidelberg Hosp, Dept Radiol, D-69120 Heidelberg, Germany. [Dinkel, J.; Eichinger, M.; Schlemmer, H. -P.] German Canc Res Ctr, Dept Radiol, Heidelberg, Germany. [Dinkel, J.; Puderbach, M.; Eichinger, M.; Heussel, C. P.; Kauczor, H. -U.; Biederer, J.] Translat Lung Res Ctr Heidelberg, Heidelberg, Germany. [Khalilzadeh, O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hintze, C.; Fabel, M.; Biederer, J.] Univ Hosp Schleswig Holstein, Dept Diagnost Radiol, Kiel, Germany. [Puderbach, M.; Heussel, C. P.] Univ Heidelberg Hosp, Dept Radiol, Thoraxklin Heidelberg, D-69120 Heidelberg, Germany. [Thorn, M.] Siemens Oncol, Forchheim, Germany. [Thomas, M.] Univ Heidelberg Hosp, Dept Oncol, Thoraxklin Heidelberg, D-69120 Heidelberg, Germany. RP Dinkel, J (reprint author), Univ Heidelberg Hosp, Dept Radiol, INF 110, D-69120 Heidelberg, Germany. EM julien.dinkel@med.uni-heidelberg.de NR 29 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2013 VL 82 IS 1 BP 76 EP 82 DI 10.1016/j.lungcan.2013.07.006 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 236XU UT WOS:000325833600012 PM 23932487 ER PT J AU Fang, SC Mehta, AJ Hang, JQ Eisen, EA Dai, HL Zhang, HX Su, L Christiani, DC AF Fang, S. C. Mehta, A. J. Hang, J. Q. Eisen, E. A. Dai, H. L. Zhang, H. X. Su, L. Christiani, D. C. TI Cotton dust, endotoxin and cancer mortality among the Shanghai textile workers cohort: a 30-year analysis SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OCCUPATIONAL RISK-FACTORS; FOLLOW-UP; PULMONARY-FUNCTION; COLORECTAL-CANCER; GASTRIC-CANCER; ESOPHAGEAL CANCER; ORGANIC DUSTS; EXPOSURE; INDUSTRY; CHINA AB Background Although occupational exposure to cotton dust and endotoxin is associated with adverse respiratory health, associations with cancer are unclear. We investigated cancer mortality in relation to cotton dust and endotoxin exposure in the Shanghai textile workers cohort. Methods We followed 444 cotton textile and a reference group of 467 unexposed silk workers for 30 years (26 777 person-years). HRs for all cancers combined (with and without lung cancer) and gastrointestinal cancer were estimated in Cox regression models as functions of cotton textile work and categories of cumulative exposure (low, medium, high), after adjustment for covariates including pack-years smoked. Different lag years accounted for disease latency. Results Risks of mortality from gastrointestinal cancers and all cancers combined, with the exclusion of lung cancer, were increased in cotton workers relative to silk workers. When stratified by category of cumulative cotton exposure, in general, risks were greatest for 20-year lagged medium exposure (all cancers HR=2.7 (95% CI 1.4 to 5.2); cancer excluding lung cancer HR=3.4 (1.7-7.0); gastrointestinal cancer HR=4.1 (1.8-9.7)). With the exclusion of lung cancer, risks of cancer were more pronounced. When stratified by category of cumulative endotoxin exposure, consistent associations were not observed for all cancers combined. However, excluding lung cancer, medium endotoxin exposure was associated with all cancers and gastrointestinal cancer in almost all lag models. Conclusions Cotton dust may be associated with cancer mortality, especially gastrointestinal cancer, and endotoxin may play a causative role. Findings also indirectly support a protective effect of endotoxin on lung cancer. C1 [Fang, S. C.; Mehta, A. J.; Eisen, E. A.; Su, L.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Fang, S. C.] New England Res Inst Inc, Div Epidemiol, Watertown, MA USA. [Mehta, A. J.] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Mehta, A. J.] Univ Basel, Basel, Switzerland. [Hang, J. Q.; Dai, H. L.; Zhang, H. X.] Putuo Dist Peoples Hosp, Dept Resp Med, Shanghai, Peoples R China. [Eisen, E. A.] Univ Calif Berkeley, Sch Publ Hlth, Dept Environm Hlth Sci, Berkeley, CA 94720 USA. [Christiani, D. C.] Massachuetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA USA. RP Fang, SC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Bldg 1 Room 1411, Boston, MA 02115 USA. EM sfang@hsph.harvard.edu FU National Institute for Occupational Safety and Health (NIOSH) [OH002421]; NIH [P50 ES00002]; American Heart Association FX This research was supported by National Institute for Occupational Safety and Health (NIOSH) grant OH002421 and NIH grant P50 ES00002. Shona Fang was supported by a grant from the American Heart Association. NR 52 TC 4 Z9 4 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD OCT PY 2013 VL 70 IS 10 BP 722 EP 729 DI 10.1136/oemed-2012-100950 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 218GQ UT WOS:000324421200009 PM 23828454 ER PT J AU Emerick, KS Leavitt, ER Michaelson, JS Diephuis, B Clark, JR Deschler, DG AF Emerick, Kevin S. Leavitt, Erica R. Michaelson, James S. Diephuis, Bradford Clark, John R. Deschler, Daniel G. TI Initial Clinical Findings of a Mathematical Model to Predict Survival of Head and Neck Cancer SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE survival; calculator; mathematical model; head neck cancer ID LYMPH-NODES CONTRIBUTES; HUMAN-PAPILLOMAVIRUS; UNITED-STATES; PRIMARY SITE; TUMOR SIZE; RISK; DEATH; CARCINOMA; IMPACT; HPV AB Objectives (1) Identify clinical features that impact survival for head and neck cancer. (2) Determine the individual contribution to mortality of significant clinical features. (3) Develop a web-based calculator to integrate clinical features and predict survival outcome for individual patients. Study Design Analysis of a national cancer database. We fit patient data to the binary-biological model of cancer lethality, a mathematical model designed to predict cancer outcome. The model predicts the risk of cancer death, using information on tumor size, nodal status, and other prognostic factors. Subjects and Methods Analysis was carried out on a cohort of ~50,000 patients with head and neck cancer from the Survey, Epidemiology and End- Results (SEER) 2009 data set and validated with a cohort of ~1300 patients from an institutional Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary database. We developed a web-based calculator written in JavaScript, PHP, and HTML. Results The risk of death due to head and neck cancer increases monotonically with tumor size. Each positive lymph node is associated with ~14% extra risk of death. Anatomical site, age, race, tumor extension, N stage, and extracapsular spread contribute to mortality. The lethal impact of these prognostics factors can be accurately estimated by the Size + Nodes + PrognosticMarkers (SNAP) method. Conclusions This predictive cancer model and web-based calculator provide a basis for estimating the risk of death for head and neck cancer patients by assigning values to the lethal contributions of tumor size, number of positive nodes, anatomical site, tumor extension, N stage, extracapsular spread, age at diagnosis, and race. C1 [Emerick, Kevin S.; Leavitt, Erica R.; Diephuis, Bradford; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Emerick, Kevin S.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Leavitt, Erica R.; Michaelson, James S.; Diephuis, Bradford] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Clark, John R.] Massachusetts Gen Hosp, Dept Med Hematol Oncol, Boston, MA 02114 USA. [Clark, John R.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Emerick, KS (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM kevin_emerick@meei.harvard.edu NR 10 TC 5 Z9 5 U1 3 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2013 VL 149 IS 4 BP 572 EP 578 DI 10.1177/0194599813495178 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 218ZR UT WOS:000324472800009 PM 23797612 ER PT J AU Fordham, MT Mulligan, JK Casey, SE Mulligan, RM Wang, EW Sansoni, ER Schlosser, RJ AF Fordham, M. Taylor Mulligan, Jennifer K. Casey, Sarah E. Mulligan, Ryan M. Wang, Eric W. Sansoni, E. Ritter Schlosser, Rodney J. TI Reactive Oxygen Species in Chronic Rhinosinusitis and Secondhand Smoke Exposure SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE chronic rhinosinusitis; reactive oxygen species; secondhand smoke; nasal polyps ID OXIDATIVE STRESS; ANTIOXIDANT BALANCE; CHRONIC SINUSITIS; DISEASES; OXIDANT; EPITHELIUM; RADICALS; EXPLANTS; ASTHMA; COPD AB Objective Reactive oxygen species (ROS) can potentiate cellular injury and inflammation. This study aimed to (1) assess the presence of reactive oxygen species in the sinus tissue of patients with chronic rhinosinusitis (CRS) and (2) assess the impact of secondhand smoke (SHS) exposure on reactive oxygen species (ROS) production. Study Design Retrospective cohort study. Setting Academic medical center. Subjects and Methods Sinus tissue samples from patients undergoing sinus surgery were analyzed using diaminobenzidine (DAB) staining to assess for ROS. Stained specimens were photographed at random by a blinded photographer and then quantified by 3 blinded graders. The patient's SHS exposure was determined by hair nicotine levels. Results were compared between non-smoke exposed cohorts and those exposed to secondhand smoke and by diagnosis. Results Sixty-nine adults undergoing sinus surgery were included in the study. For the non-SHS-exposed cohorts, chronic rhinosinusitis with nasal polyps (CRSwNP) had the highest number of DAB+ cells/high-powered field (hpf) followed by chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. When comparing the control patients to their SHS-exposed counterparts, SHS exposure yielded statistically significantly higher levels of DAB-positive cells/hpf. SHS exposure did not affect DAB staining in CRSsNP or CRSwNP patients. Conclusion ROS are differentially expressed in various subtypes of CRS. SHS exposure increases ROS in sinus tissue of control patients, but the clinical significance of this is unclear. C1 [Fordham, M. Taylor; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Mulligan, Jennifer K.; Wang, Eric W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Casey, Sarah E.; Mulligan, Ryan M.; Wang, Eric W.; Sansoni, E. Ritter; Schlosser, Rodney J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. RP Fordham, MT (reprint author), Med Univ S Carolina, Dept Otolaryngol, MSC 550,135 Rutledge Ave, Charleston, SC 29425 USA. EM fordham@musc.edu OI Wang, Eric/0000-0002-1180-5854 FU AAO CORE Resident Research Grant; Flight Attendant Medical Research Institute; VA Merit Grant FX AAO CORE Resident Research Grant, Flight Attendant Medical Research Institute, VA Merit Grant. NR 27 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2013 VL 149 IS 4 BP 633 EP 638 DI 10.1177/0194599813496377 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 218ZR UT WOS:000324472800018 PM 23838308 ER PT J AU Harmon, T Worrall, TJ AF Harmon, Timothy Worrall, Thomas J. TI Retrospective case-control study comparing twice daily insulin glargine and insulin detemir in veteran patients with type 2 diabetes SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 13-16, 2013 CL Albuquerque, NM SP Amer Coll Clin Pharm C1 [Harmon, Timothy] Ralph H Johnson VAMC, Charleston, SC USA. [Worrall, Thomas J.] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2013 VL 33 IS 10 MA 10 BP E184 EP E184 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230RM UT WOS:000325360100038 ER PT J AU Higginson, A Pfeifer, M Roberti, A Yi, S McGregor, JC Manning, J Hinton, K Singh, H AF Higginson, Amy Pfeifer, Michelle Roberti, Angie Yi, Stellar McGregor, Jessina C. Manning, Jane Hinton, Kristina Singh, Harleen TI Conversion of Veterans Affairs Patients to Combivent Respimat: A patient follow-up to evaluate adherence, appropriate use, and symptom control. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 13-16, 2013 CL Albuquerque, NM SP Amer Coll Clin Pharm C1 [Higginson, Amy; Pfeifer, Michelle; Roberti, Angie; Yi, Stellar; Singh, Harleen] Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, Portland, OR USA. [Manning, Jane] Portland VA Med Ctr, Portland, OR USA. [Hinton, Kristina] Portland VA Med Ctr, Vancouver, WA 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2013 VL 33 IS 10 MA 375 BP E294 EP E294 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230RM UT WOS:000325360100403 ER PT J AU Vakil, N Levine, A Lin, H Newman, K Lyman, C Yeh, D Hooper, D Varughese, C AF Vakil, Niyati Levine, Alexander Lin, Hsin Newman, Kelly Lyman, Christopher Yeh, Daniel Hooper, David Varughese, Christy TI Clinical utility of rectal swabs as a predictor of vancomycin-resistant enterococcal infections requiring antibiotic treatment. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 13-16, 2013 CL Albuquerque, NM SP Amer Coll Clin Pharm C1 [Vakil, Niyati; Levine, Alexander; Lin, Hsin; Newman, Kelly; Lyman, Christopher; Varughese, Christy] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Yeh, Daniel] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hooper, David] Massachusetts Gen Hosp, Dept Infect Dis, 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2013 VL 33 IS 10 MA 119E BP E218 EP E218 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230RM UT WOS:000325360100147 ER PT J AU Woolley, AB Scarlatos, M Saunders, S AF Woolley, Adam B. Scarlatos, Maria Saunders, Shawn TI Creation and implementation of a web-based home-grown pharmacy intervention system using Microsoft SharePoint (R) SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 13-16, 2013 CL Albuquerque, NM SP Amer Coll Clin Pharm C1 [Woolley, Adam B.; Scarlatos, Maria] Northeastern Univ, Sch Pharm, Boston, MA 02115 USA. [Saunders, Shawn] VA Boston Healthcare Syst, West Roxbury, MA 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2013 VL 33 IS 10 MA 250 BP E257 EP E257 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230RM UT WOS:000325360100278 ER PT J AU Elman, I Borsook, D Volkow, ND AF Elman, Igor Borsook, David Volkow, Nora D. TI Pain and suicidality: Insights from reward and addiction neuroscience SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Anti-reward; Homeostasis; Allostasis; Habenula; Stress; Cross-sensitization; Aberrant learning ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; SELF-INJURIOUS-BEHAVIOR; INTERPERSONAL-PSYCHOLOGICAL THEORY; NATIONAL-COMORBIDITY-SURVEY; IRRITABLE-BOWEL-SYNDROME; DEFICIENCY SYNDROME RDS; OPPONENT-PROCESS THEORY; FREELY MOVING RATS; CHRONIC BACK-PAIN AB Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain-and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. Published by Elsevier Ltd. C1 [Elman, Igor] Harvard Univ, Sch Med, Providence VA Med Ctr, Somerville, MA 02143 USA. [Elman, Igor] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Somerville, MA 02143 USA. [Borsook, David] Boston Childrens Hosp, PAIN Grp, Dept Anesthesiol, Boston, MA USA. [Borsook, David] Massachusetts Gen Hosp, Dept Radiol, Dept Psychiat & Radiol, Boston, MA 02114 USA. [Borsook, David] Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Boston, MA 02115 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Elman, I (reprint author), Harvard Univ, Sch Med, Providence VA Med Ctr, 26 Cent St, Somerville, MA 02143 USA. EM ielman@cha.harvard.edu FU Mayday Fund/Herlands Fund for Pain Systems Neuroscience Research; Providence VA Medical Center FX The authors gratefully acknowledge Ms. Adriana Johnson for her help with the preparation of the manuscript and support from the Mayday Fund/Herlands Fund for Pain Systems Neuroscience Research (DB).; This study was supported with resources and the use of facilities at the Providence VA Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. NR 467 TC 42 Z9 42 U1 7 U2 54 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD OCT PY 2013 VL 109 BP 1 EP 27 DI 10.1016/j.pneurobio.2013.06.003 PG 27 WC Neurosciences SC Neurosciences & Neurology GA 238AO UT WOS:000325913000001 PM 23827972 ER PT J AU Ranganath, VK Maranian, P Elashoff, DA Woodworth, T Khanna, D Hahn, T Sarkisian, C Kremer, JM Furst, DE Paulus, HE AF Ranganath, Veena K. Maranian, Paul Elashoff, David A. Woodworth, Thasia Khanna, Dinesh Hahn, Theodore Sarkisian, Catherine Kremer, Joel M. Furst, Daniel E. Paulus, Harold E. TI Comorbidities are associated with poorer outcomes in community patients with rheumatoid arthritis SO RHEUMATOLOGY LA English DT Article DE comorbidities; rheumatoid arthritis; age; remission ID LESS AGGRESSIVE TREATMENT; MINIMAL DISEASE-ACTIVITY; PHYSICAL FUNCTION; CORRONA REGISTRY; ELDERLY-PATIENTS; UNITED-STATES; REMISSION; ETANERCEPT; AGE; POPULATION AB Objective. To evaluate the impact of comorbidities on achieving remission by examining changes in the clinical disease activity index (CDAI) in RA patients in the community-based Consortium of Rheumatology Researchers of North America (CORRONA) registry. Methods. A subcohort of 1548 RA subjects with varying disease duration met the following inclusion criteria: started a DMARD/biologic agent, continued therapy 53 months, CDAI 52.8 at study entry and followed longitudinally from baseline to follow-up (mean time 7.46 months). Patients reported comorbidities according to a standardized list of 33 conditions. Entry characteristics were compared across age categories using one-way analysis of variance. Linear and logistic regression models were constructed to assess characteristics [e. g. age, disease duration, number of previous DMARDs/biologics, baseline modified health assessment questionnaire (MHAQ), baseline CDAI and number of comorbidities] associated with primary outcomes: change in CDAI (baseline to follow-up) and CDAI remission (yes/no). Results. Although disease activity measures at entry were similar across age categories, older patients had more comorbidities, less improvement in CDAI/MHAQ and were less likely to attain remission at follow-up. However, after adjusting covariates an increasing number of patient-reported comorbidities and higher baseline CDAI (but not age) were consistently and independently associated with a lower likelihood of clinical improvement or remission (P<0.001). Conclusion. In this observational cohort of community RA patients an increasing number of patients reported comorbidities, independently correlated with less CDAI improvement over time. These results reaffirm that comorbidities may be an important factor in consideration of treat-to-target recommendations and aid in understanding achievable RA therapeutic goals. C1 [Ranganath, Veena K.; Maranian, Paul; Woodworth, Thasia; Furst, Daniel E.; Paulus, Harold E.] Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Elashoff, David A.] Univ Calif Los Angeles, Dept Med & Biostat, Los Angeles, CA 90095 USA. [Khanna, Dinesh] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Hahn, Theodore; Sarkisian, Catherine] Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Dept Med, Los Angeles, CA USA. [Kremer, Joel M.] Albany Med Coll, Ctr Rheumatol, Albany, NY 12208 USA. RP Ranganath, VK (reprint author), Univ Calif Los Angeles, 1000 Veteran Ave,Rehab Bldg 32-59, Los Angeles, CA 90095 USA. EM vranganath@mednet.ucla.edu FU ACR/REF/ASP Junior Career Development Award in Geriatric Medicine; National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health [NIAMS K23 AR057818-02]; Scleroderma Foundation; National Institutes of Health Award [NIAMS K23 AR053858-04]; Abbvie; Actelion; Amgen; BMS; Gilead; GSK; NIH; Novartis; Pfizer; Roche/Genentech; UCB; Biogen Idec; Janssen; Genetech FX The authors thank Janet Elashoff, PhD, for her editorial comments and insightful discussions. The ACR/REF/ASP Junior Career Development Award in Geriatric Medicine was awarded to V. K. R. The National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under award number NIAMS K23 AR057818-02 helped to support V. K. R. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The New Investigator Award from the Scleroderma Foundation and the National Institutes of Health Award (NIAMS K23 AR053858-04) helped to support D.K.'s time.; Disclosure statement: D. E. F is a consultant for and received honoraria and research grants/research support from Abbvie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Biogen Idec and Janssen. J.M.K. is a consultant for Abbvie, Amgen, BMS, Genetech, Pfizer, UCB and Vertex and has received grants from Abbvie, Amgen, BMS, Genetech and Pfizer. All other authors have declared no conflicts of interest. NR 47 TC 20 Z9 21 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD OCT PY 2013 VL 52 IS 10 BP 1809 EP 1817 DI 10.1093/rheumatology/ket224 PG 9 WC Rheumatology SC Rheumatology GA 239CA UT WOS:000325997900013 PM 23813577 ER PT J AU Lawasut, P Groen, RWJ Dhimolea, E Richardson, PG Anderson, KC Mitsiades, CS AF Lawasut, Panisinee Groen, Richard W. J. Dhimolea, Eugen Richardson, Paul G. Anderson, Kenneth C. Mitsiades, Constantine S. TI Decoding the Pathophysiology and the Genetics of Multiple Myeloma to Identify New Therapeutic Targets SO SEMINARS IN ONCOLOGY LA English DT Review ID PLASMA-CELL LEUKEMIA; NF-KAPPA-B; BONE-MARROW; IN-VIVO; MOLECULAR PATHOGENESIS; ANTIMYELOMA ACTIVITY; SUPPRESSOR-CELLS; ANTITUMOR-ACTIVITY; DENDRITIC CELLS; STROMAL CELLS AB In recent years, significant progress has been achieved in the characterization of the transcriptional profiles, gene mutations and structural chromosomal lesions in myeloma cells. These studies have identified many candidate therapeutic targets, which are recurrently deregulated in myeloma cells. However, these targets do not appear, at least individually, to represent universal driver(s) of this disease. Furthermore, evaluation of these recurrent lesions does not suggest that they converge to a single molecular pathway. Detailed integration of molecular and functional data for these candidate targets and pathways will hopefully dissect which of them play more critical roles for each of the different individual molecular defined subtypes of this disease. This review focuses on how recent updates in our understanding of myeloma pathogenesis and molecular characterization may impact ongoing and future efforts to develop new therapeutics for this disease. (C) 2013 Published by Elsevier Inc. C1 [Lawasut, Panisinee; Groen, Richard W. J.; Dhimolea, Eugen; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lawasut, Panisinee; Groen, Richard W. J.; Dhimolea, Eugen; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lawasut, Panisinee] King Chulalongkorn Mem Hosp, Fac Med, Dept Med, Div Hematol, Bangkok, Thailand. [Lawasut, Panisinee] Chulalongkorn Univ, Thai Red Cross Soc, Bangkok, Thailand. [Groen, Richard W. J.] Univ Med Ctr Utrecht, Dept Cell Biol, Utrecht, Netherlands. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, 450 Brookline Ave,Harvard Inst Med Bldg,Room HIM3, Boston, MA 02115 USA. EM Constantine_Mitsiades@dfci.harvard.edu OI Groen, Richard/0000-0002-5010-4604 FU Shawna Ash lee Corman Investigatorship in Multiple Myeloma Research; Multiple Myeloma Research Foundation; Leukemia and Lymphoma Society; de Gunzburg Myeloma Research Fund; NIH [R01CA050947, P01CA155258]; European Union [302428] FX C.S.M. is supported by the Shawna Ash lee Corman Investigatorship in Multiple Myeloma Research; the Multiple Myeloma Research Foundation, and the Leukemia and Lymphoma Society. C.S.M. and P.G.R. are supported by the de Gunzburg Myeloma Research Fund. C.S.M. and K.C.A. are supported by NIH grants R01CA050947 and P01CA155258. is supported by the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/ under REA grant agreement No [302428]. The authors would like to acknowledge the assistance of Jeffrey D. Sorrell in the preparation of the manuscript. NR 125 TC 2 Z9 2 U1 0 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2013 VL 40 IS 5 BP 537 EP 548 DI 10.1053/j.seminoncol.2013.07.010 PG 12 WC Oncology SC Oncology GA 239DR UT WOS:000326003300003 PM 24135398 ER PT J AU Laubach, J Hideshima, T Richardson, P Anderson, K AF Laubach, Jacob Hideshima, Teru Richardson, Paul Anderson, Kenneth TI Clinical Translation in Multiple Myeloma: From Bench to Bedside SO SEMINARS IN ONCOLOGY LA English DT Review ID PROTEASOME INHIBITOR PS-341; STEM-CELL TRANSPLANTATION; THALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED PHASE-III; COMBINATION CHEMOTHERAPY; BONE-MARROW; ANTIMYELOMA ACTIVITY; REFRACTORY MYELOMA; ELDERLY-PATIENTS; DRUG-RESISTANCE AB The outlook for patients with multiple myeloma (MM) has improved significantly with the development of new and more effective therapies, particularly the immunomodulatory agents and proteasome inhibitors. Preclinical and correlative science investigations have played a critical role in these advances, providing important insights regarding mechanisms of neoplasia, inhibition of tumor growth, and drug resistance. This review highlights the evolution of drug development in MM, the manner in which preclinical models have contributed to the process of drug discovery, and important insights gained during the current era of MM drug development. (C) 2013 Elsevier Inc. All rights reserved. C1 [Laubach, Jacob; Hideshima, Teru; Richardson, Paul; Anderson, Kenneth] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Laubach, Jacob; Hideshima, Teru; Richardson, Paul; Anderson, Kenneth] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Laubach, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM jacob_laubach@dfci.harvard.edu NR 57 TC 4 Z9 4 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 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2013 VL 40 IS 5 BP 549 EP 553 DI 10.1053/j.seminoncol.2013.07.009 PG 5 WC Oncology SC Oncology GA 239DR UT WOS:000326003300004 PM 24135399 ER PT J AU Girnius, S Munshi, NC AF Girnius, Saulius Munshi, Nikhil C. TI Individualized Therapy in Multiple Myeloma: Are We There? SO SEMINARS IN ONCOLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; INTERNATIONAL STAGING SYSTEM; IN-SITU HYBRIDIZATION; HIGH-RISK CYTOGENETICS; FREE LIGHT-CHAIN; MOLECULAR REMISSION; AUTOLOGOUS TRANSPLANTATION; INTERGROUPE FRANCOPHONE; EXPRESSION SIGNATURE AB Multiple myeloma (MM), a heterogeneous plasma cell dyscrasia with a variety of clinical presentations and outcomes, is undergoing a treatment renaissance. While new drug classes have been discovered, a subset of high-risk MM remains relatively refractory to treatment. Current risk stratifications models, such as Dude-Salmon and the International Staging System, estimate disease burden and prognosis. Cytogenetics and gene expression profiles can help further identify more aggressive disease. Additionally, molecular and immunophenotypic assessment of minimal residual disease (MRD) and different imaging studies can identify patients at higher risk for relapse. It is now an opportune time to develop algorithms to combine all of the currently available clinical and genomic information to begin to inform specific therapeutic intervention in individual patients or at least smaller subgroups with similarly behaving disease. (C) 2013 Published by Elsevier Inc. C1 [Girnius, Saulius; Munshi, Nikhil C.] Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Girnius, Saulius] Boston Med Ctr, Boston, MA USA. [Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 450 Brookline St,M230, Boston, MA 02215 USA. EM Nikhil_Munshi@dfci.harvard.edu FU Department of Veterans Affairs [I01-BX001584]; National Institutes of Health [RO1-124929, PO1-155258, P50-100007, PO1-78378] FX Supported in part by the Department of Veterans Affairs Merit Review Award No. I01-BX001584 and from the National Institutes of Health Grants No. RO1-124929, PO1-155258, P50-100007, and PO1-78378. NR 66 TC 6 Z9 6 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2013 VL 40 IS 5 BP 567 EP 576 DI 10.1053/j.seminoncol.2013.08.001 PG 10 WC Oncology SC Oncology GA 239DR UT WOS:000326003300006 PM 24135401 ER PT J AU Rosenbaum, C Jasielec, J Laubach, J Prada, CP Richardson, P Jakubowiak, AJ AF Rosenbaum, Cara Jasielec, Jagoda Laubach, Jacob Prada, Claudia Paba Richardson, Paul Jakubowiak, Andrzej J. TI Evolving Strategies in the Initial Treatment of Multiple Myeloma SO SEMINARS IN ONCOLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; BORTEZOMIB-THALIDOMIDE-DEXAMETHASONE; MULTIPARAMETER FLOW-CYTOMETRY; MINIMAL RESIDUAL DISEASE; FREE LIGHT-CHAIN; PHASE-III TRIAL; COMPLETE RESPONSE; RANDOMIZED PHASE-3; AUTOLOGOUS TRANSPLANTATION AB Until the advents of novel agents, partial response (PR) or better was the established gold standard to initial therapy of multiple myeloma (MM), and treatment goals were focused on relieving symptoms, prevention of organ damage, and modest improvements in survival. With the introduction of autologous stem cell transplant (ASCT), deeper responses, including complete responses (CRs) were more frequent, and contributed to longer survival. In the era of novel therapies, ASCT remains commonly used and its impact on outcome appears superior, albeit less so than when compared with conventional therapy, and its survival benefit is yet to be established in either setting. In addition, in non-transplant candidates, novel therapies have now significantly improved the overall response rates, depth of response, and clinical benefit, to the levels previously only observed with ASCT, which now increasingly challenges the role and timing of ASCT in eligible patients. Nevertheless, the two approaches of treatment, transplant or no transplant, remain commonly accepted. With an improvement in the tolerability of newer regimens and the deferral of ASCT in transplant candidates, the debate has emerged whether the two-pathway approach to the treatment of newly diagnosed myeloma should be re-evaluated. At the same time, treatment goals are also shifting. Many believe that MM can be converted into a chronic disease and that a functional cure maybe a realistic goal, for at least a proportion of patients. This contribution will review these points of discussion and the evolving approach to treatment of newly diagnosed MM. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rosenbaum, Cara; Jasielec, Jagoda; Jakubowiak, Andrzej J.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Rosenbaum, Cara; Jakubowiak, Andrzej J.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA. [Laubach, Jacob; Prada, Claudia Paba; Richardson, Paul] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Boston, MA 02115 USA. RP Jakubowiak, AJ (reprint author), Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM ajakubowiak@medicine.bsd.uchicago.edu FU GlaxoSmithKline FX C.R. has received research funding from GlaxoSmithKline and has had speaking engagements with Celgene Corp with honoraria. A.J.J. served on advisory boards or as a consultant for Bristol-Myers Squibb, Celgene, Janssen-Cilag, Millennium Pharmaceuticals, and Onyx Pharmaceuticals, and has speaking engagements with Celgene and Onyx Pharmacuticals with honoraria. P.G.R. serves on advisory boards for Celgene, Millennium Pharmaceuticals, Johnson & Johnson, Bristol-Myers Squibb, and Novartis. J. J., J.L., and C.P.P. have no disclosures to declare. NR 67 TC 2 Z9 2 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 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2013 VL 40 IS 5 BP 592 EP 601 DI 10.1053/j.seminoncol.2013.08.002 PG 10 WC Oncology SC Oncology GA 239DR UT WOS:000326003300009 PM 24135404 ER PT J AU Pos, W Sethi, DK Wucherpfennig, KW AF Pos, Wouter Sethi, Dhruv K. Wucherpfennig, Kai W. TI Mechanisms of peptide repertoire selection by HLA-DM SO TRENDS IN IMMUNOLOGY LA English DT Review DE antigen presentation; MHC class II molecules ID DIABETOGENIC T-CELLS; ANTIGEN PRESENTATION; CRYSTAL-STRUCTURE; CUTTING EDGE; DR MOLECULES; COMPLEXES; AUTOIMMUNITY; STABILITY; REGISTER; PATHWAY AB Recently, crystal structures of key complexes in antigen presentation have been reported. HLA-DM functions in antigen presentation by catalyzing dissociation of an invariant chain remnant from the peptide binding groove and stabilizing empty MHC class II proteins in a peptide-receptive conformation. The crystal structure of a MHC class II-HLA-DM complex explains how HLA-DM stabilizes an otherwise short-lived transition state and promotes a rapid peptide exchange process that favors the highest-affinity ligands. HLA-DO has sequence similarity with MHC class II molecules yet inhibits antigen presentation. The structure of the HLA-DO-HLA-DM complex shows that it blocks HLA-DM activity as a substrate mimic. Alterations in the efficiency of DM-mediated peptide selection may contribute to autoimmune pathologies, which will be an exciting area for future investigation. C1 [Pos, Wouter; Sethi, Dhruv K.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU National Institutes of Health [RO1 NS044914, PO1 AI045757]; National Multiple Sclerosis Society; American Diabetes Association FX We would like to thank Melissa J. Call, Monika-Sarah E. D. Schulze, Anne-Kathrin Anders, Jason Pyrdol, and Eric J. Sundberg for their important contributions to work reviewed here. This work was supported by grants from the National Institutes of Health (RO1 NS044914 and PO1 AI045757 to K.W.W.), postdoctoral fellowships from The National Multiple Sclerosis Society (D.K.S.) and the American Diabetes Association (W.P.). NR 34 TC 15 Z9 15 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD OCT PY 2013 VL 34 IS 10 BP 495 EP 501 DI 10.1016/j.it.2013.06.002 PG 7 WC Immunology SC Immunology GA 240XJ UT WOS:000326130700004 PM 23835076 ER PT J AU Jakobiec, FA Mendoza, PR Colby, KA AF Jakobiec, Frederick A. Mendoza, Pia R. Colby, Kathryn A. TI Clinicopathologic and Immunohistochemical Studies of Conjunctival Large Cell Acanthoma, Epidermoid Dysplasia, and Squamous Papilloma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; CYTOKERATIN EXPRESSION; KERATIN 13; CARCINOMA; EPITHELIUM; CORNEA; P53; LEUKOPLAKIA; KERATOSIS; SPECTRUM AB PURPOSE: To evaluate clinicopathologically and immunohistochemically a spectrum of conjunctival squamous proliferations. DESIGN: Retrospective clinicopathologic study. METHODS: One large cell acanthoma, 7 epidermoid dysplasias, and 4 squamous papillomas were evaluated with microscopy and biomarkers Ki-67, p53, epithelial membrane antigen (EMA), Ber-EP4, AE1, AE3, and 8 individual cytokeratins. Normal associated conjunctiva served as a baseline for interpretation. RESULTS: The large cell acanthoma recurred 4 times but retained its benign histopathologic features. The cells were 2-3 times larger than the keratinocytes of the normal conjunctiva and did not display atypia. Immunohistochemistry revealed a low Ki-67 proliferation index (PI) in the large cell acanthoma compared with high indices in dysplasias and papillomas. p53 was negative in the nuclei of normal epithelium while positive in all neoplasms, most intensely in the dysplasias. Immunostaining showed similar staining patterns for cytokeratins in large cell acanthoma and normal conjunctiva, except for full-thickness CK14 positivity and CK7 negativity in the lesion. Dysplasias generally lost normal CK7 expression and frequently abnormally expressed CK17. The papillomas displayed a normal cytokeratin pattern but exhibited a higher than normal PI and weak p53 positivity. CONCLUSIONS: Conjunctival large cell acanthoma is a morphologically distinctive clonal entity with clinical and immunohistochemical phenotypic characteristics denoting a dysplasia of minimal severity. Because of recurrences without invasion, it requires treatment. Dysplasias exhibited more deviant biomarker abnormalities including frequent aberrant full-thickness CK17 positivity and CK7 negativity. The absence of major cytokeratin derangements in the squamous papillomas may be of ancillary diagnostic value for lesions displaying borderline cytologic features. ((c) 2013 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.; Mendoza, Pia R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Colby, Kathryn A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea Serv, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Mendoza, Pia R.; Colby, Kathryn A.] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St Suite 328, Boston, MA 02114 USA. EM Fred_jakobiec@meei.harvard.edu NR 48 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2013 VL 156 IS 4 BP 830 EP 846 DI 10.1016/j.ajo.2013.05.005 PG 17 WC Ophthalmology SC Ophthalmology GA 231VT UT WOS:000325447200027 PM 23786782 ER PT J AU Bachiller, PR Cornog, KH Kato, R Buys, ES Roberts, JD AF Bachiller, Patricia R. Cornog, Katherine H. Kato, Rina Buys, Emmanuel S. Roberts, Jesse D., Jr. TI Soluble guanylate cyclase modulates alveolarization in the newborn lung SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE soluble guanylate cyclase; cGMP; lung development; alveolarization ID DEPENDENT PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE SYNTHASE; RIGHT-VENTRICULAR HYPERTROPHY; RAT LUNG; MOUSE LUNG; PULMONARY-HYPERTENSION; NEONATAL MICE; BRONCHOPULMONARY DYSPLASIA; POSTNATAL-GROWTH AB Nitric oxide (NO) regulates lung development through incompletely understood mechanisms. NO controls pulmonary vascular smooth muscle cell (SMC) differentiation largely through stimulating soluble guanylate cyclase (sGC) to produce cGMP and increase cGMP-mediated signaling. To examine the role of sGC in regulating pulmonary development, we tested whether decreased sGC activity reduces alveolarization in the normal and injured newborn lung. For these studies, mouse pups with gene-targeted sGC-alpha 1 subunit truncation were used because we determined that they have decreased pulmonary sGC enzyme activity. sGC-alpha 1 knockout (KO) mouse pups were observed to have decreased numbers of small airway structures and lung volume compared with wild-type (WT) mice although lung septation and body weights were not different. However, following mild lung injury caused by breathing 70% O-2, the sGC-alpha 1 KO mouse pups had pronounced inhibition of alveolarization, as evidenced by an increase in airway mean linear intercept, reduction in terminal airway units, and decrease in lung septation and alveolar openings, as well as reduced somatic growth. Because cGMP regulates SMC phenotype, we also tested whether decreased sGC activity reduces lung myofibroblast differentiation. Cellular markers revealed that vascular SMC differentiation decreased, whereas myofibroblast activation increased in the hyperoxic sGC-alpha 1 KO pup lung. These results indicate that lung development, particularly during hyperoxic injury, is impaired in mouse pups with diminished sGC activity. These studies support the investigation of sGC-targeting agents as therapies directed at improving development in the newborn lung exposed to injury. C1 [Bachiller, Patricia R.; Kato, Rina; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Bachiller, Patricia R.; Buys, Emmanuel S.; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bachiller, Patricia R.; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Cornog, Katherine H.] Applied Video Res, Medford, MA USA. RP Roberts, JD (reprint author), Massachusetts Gen Hosp East, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM roberts@cvrc.mgh.harvard.edu FU National Institutes of Health [5T32GM0759, 1R01HL096779]; Foundation for Anesthesia Education and Research (MRTG); American Heart Association [10SDG2610313]; Ikaria/INO Therapeutics; Harvard Medical School; MGH Department of Anesthesia, Critical Care, and Pain Medicine FX This work was supported by the National Institutes of Health (5T32GM0759 to P. Bachiller and 1R01HL096779 to J. Roberts), the Foundation for Anesthesia Education and Research (MRTG to P. Bachiller), the American Heart Association (Scientist Development Grant 10SDG2610313 to E. Buys), Ikaria/INO Therapeutics, the Harvard Medical School (Shore Fellowship to P. Bachiller), and the MGH Department of Anesthesia, Critical Care, and Pain Medicine. NR 79 TC 15 Z9 15 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD OCT PY 2013 VL 305 IS 8 BP L569 EP L581 DI 10.1152/ajplung.00401.2012 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 236OQ UT WOS:000325808900005 PM 23934926 ER PT J AU Smith, MW Bentley, MA Fernandez, AR Gibson, G Schweikhart, SB Woods, DD AF Smith, Michael W. Bentley, Melissa A. Fernandez, Antonio R. Gibson, Gregory Schweikhart, Sharon B. Woods, David D. TI Performance of Experienced Versus Less Experienced Paramedics in Managing Challenging Scenarios: A Cognitive Task Analysis Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID HEALTH-CARE; EXPERTISE; SCENE; WORK AB Study objective: Out-of-hospital care is becoming more complex, thus placing greater reliance on the cognitive abilities of paramedics to manage difficult situations. In adapting to the challenges in their work, paramedics develop expertise. We study the cognitive strategies used by expert paramedics to contribute to understanding how paramedics and the EMS system can adapt to new challenges. Methods: We conducted a "staged-world" cognitive task analysis to explore paramedics' handling of cognitive challenges related to sense-making and to resource and task management. A mixed-fidelity simulation was used to present paramedics with 2 challenging scenarios: a pulmonary embolism initially presenting as a myocardial infarction and a 2-person shooting with limited resources available. Results: Participants were 10 paramedics, 6 more experienced and 4 less experienced. Analysis involved comparing the performance of the 2 groups to identify strategies associated with expertise. The more experienced paramedics made more assessments, explored a wider variety of presumptive diagnoses, and identified the pulmonary embolism earlier. They switched attention between the 2 shooting victims more, used their emergency medical technician basic level partners more, and provided more advanced level care for both patients. Their patients arrived at the emergency department more prepared for specialized emergency care. Conclusion: Our findings correspond to general cognitive attributes of expertise: greater cue gathering and inferential reasoning, and more functional and strategic thinking. These results suggest potential areas and methods to facilitate development of expertise, as well as ways to better support use of expertise. Future studies should expand on these findings through larger sample sizes and more complex scenarios. C1 [Smith, Michael W.; Woods, David D.] Ohio State Univ, Cognit Syst Engn Lab, Inst Ergon, Columbus, OH 43210 USA. [Schweikhart, Sharon B.] Ohio State Univ, Div Hlth Serv Management & Policy, Columbus, OH 43210 USA. [Smith, Michael W.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Smith, Michael W.] Baylor Coll Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Smith, Michael W.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Bentley, Melissa A.] Natl Registry Emergency Med Tech, Columbus, OH USA. [Fernandez, Antonio R.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA. [Gibson, Gregory] Kent State Univ, Dept Sociol, Kent, OH 44242 USA. RP Smith, MW (reprint author), Ohio State Univ, Cognit Syst Engn Lab, Inst Ergon, Columbus, OH 43210 USA. EM ms6@bcm.edu FU National Registry of Emergency Medical Technicians; Google Research Award; Department of Integrated Systems Engineering, College of Engineering, Ohio State University FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. This research was supported by the National Registry of Emergency Medical Technicians, a Google Research Award, and the Department of Integrated Systems Engineering, College of Engineering, Ohio State University. NR 52 TC 5 Z9 5 U1 1 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 BP 367 EP 379 DI 10.1016/j.annemergmed.2013.04.026 PG 13 WC Emergency Medicine SC Emergency Medicine GA 229ZZ UT WOS:000325307700016 PM 23787209 ER PT J AU Borczuk, P Penn, J Benzer, T Peak, D AF Borczuk, P. Penn, J. Benzer, T. Peak, D. TI Emergency Department Observation of Patients With Traumatic Intracranial Hemorrhage SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Winchester Hosp, Winchester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S6 EP S7 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500015 ER PT J AU Burke, TF Nelson, BD Eckardt, M Dulo, L Ogurtu, M Maua, J Qureshi, Z Ahn, R AF Burke, T. F. Nelson, B. D. Eckardt, M. Dulo, L. Ogurtu, M. Maua, J. Qureshi, Z. Ahn, R. TI Ultra-Low Cost Uterine Balloon Tamponade Package for Postpartum Hemorrhage Control Among Health Providers in Kenya SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Boston, MA 02114 USA. African Inst Innovat & Technol, Kisumu, Kenya. Univ Nairobi, Sch Med, Nairobi, Kenya. NR 0 TC 1 Z9 1 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S101 EP S102 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500278 ER PT J AU Chambers, JG Kabrhel, C Venkatesh, AK Schuur, JD AF Chambers, Gibson J. Kabrhel, C. Venkatesh, A. K. Schuur, J. D. TI US Hospital Variation in Outpatient Treatment of Venous Thromboembolic Disease, 2010 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Univ New England, Biddeford, ME USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S61 EP S62 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500162 ER PT J AU Chambers, JG Kabrhel, C Venkatesh, AK Schuur, JD AF Chambers, Gibson J. Kabrhel, C. Venkatesh, A. K. Schuur, J. D. TI Prevalence and Patient Predictors in Outpatient Treatment of Venous Thromboembolic Disease SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Univ New England, Biddeford, ME USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S36 EP S36 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500092 ER PT J AU Douglass, ER Henwood, PC Rempell, JS Murray, AF Liteplo, AS Krebs, EA Dukundane, D Rulisa, S Dean, AJ Noble, VE AF Douglass, E. R. Henwood, P. C. Rempell, J. S. Murray, A. F. Liteplo, A. S. Krebs, E. A. Dukundane, D. Rulisa, S. Dean, A. J. Noble, V. E. TI Sustained Knowledge Acquisition Among Rwandan Physicians Participating in Six-Month Ultrasound Training Program SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Duke Univ, Dept Emergency Med, Durham, NC USA. Univ Teaching Hosp Kigali, Kigali, Rwanda. Hosp Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S33 EP S34 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500084 ER PT J AU Gaspari, R Liteplo, A Polan, D Sulaibikh, AA Blehar, D AF Gaspari, R. Liteplo, A. Polan, D. Sulaibikh, A. A. Blehar, D. TI The Massachusetts Abscess Rule: A Decision Rule for Soft Tissue Ultrasound That Excludes MRSA SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 UMASS, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RI Gaspari, Romolo/I-4649-2014 OI Gaspari, Romolo/0000-0002-8411-0308 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S6 EP S6 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500014 ER PT J AU Geyer, B Peak, DA Gates, JD Velmahos, GC Michaud, Y Petrovick, L Raja, A AF Geyer, B. Peak, D. A. Gates, J. D. Velmahos, G. C. Michaud, Y. Petrovick, L. Raja, A. TI Decreased Imaging Use Associated With Transfer Of Trauma Patients Within an Accountable Care Organization SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Mass Gen Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S66 EP S67 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500176 ER PT J AU Geyer, B Peak, DA Velmahos, GC Gates, JD Petrovick, L Michaud, Y Growe, A Sullivan, D Raja, A AF Geyer, B. Peak, D. A. Velmahos, G. C. Gates, J. D. Petrovick, L. Michaud, Y. Growe, A. Sullivan, D. Raja, A. TI Cost Savings Associated With Transfer Of Trauma Patients Within An Accountable Care Organization SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Mass Gen Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Partners Healthcare Finance, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S62 EP S62 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500163 ER PT J AU Geyer, BC Gates, J Lee, J Shah, K Raja, AS AF Geyer, B. C. Gates, J. Lee, J. Shah, K. Raja, A. S. TI Implementation of a Tranexamic Acid Protocol in the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Hosp, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S31 EP S31 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500077 ER PT J AU Henwood, PC Rempell, JS Liteplo, AS Leo, MM Murray, AF Mackenzie, D Vaillancourt, S Rulisa, S Dean, AJ Noble, VE AF Henwood, P. C. Rempell, J. S. Liteplo, A. S. Leo, M. M. Murray, A. F. Mackenzie, D. Vaillancourt, S. Rulisa, S. Dean, A. J. Noble, V. E. TI Point-of-Care Ultrasound Use Over Six-Month Training Period in Rwandan District Hospitals SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Univ Toronto, Toronto, ON, Canada. Univ Teaching Hosp Kigali, Kigali, Rwanda. Hosp Univ Penn, Philadelphia, PA 19104 USA. RI Vaillancourt, Samuel/B-7170-2016 OI Vaillancourt, Samuel/0000-0001-7561-2368 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S77 EP S78 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500210 ER PT J AU Lee, J Raja, A Filbin, M Hwabejire, J Kaafarani, H Yeh, D Velmahos, G Marc, DM Matthias, E Shah, K AF Lee, J. Raja, A. Filbin, M. Hwabejire, J. Kaafarani, H. Yeh, D. Velmahos, G. Marc, D. M. Matthias, E. Shah, K. TI Mandatory Health Care Insurance is Not Associated With Improved Mortality or ICU Length of Stay in Severely Injured Trauma Patients in Massachusetts SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp Ctr, Boston, MA USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S27 EP S27 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500068 ER PT J AU Liteplo, AS Noble, VE Marill, KA Dipre, M Huang, C AF Liteplo, A. S. Noble, V. E. Marill, K. A. Dipre, M. Huang, C. TI INSPIRED (Instruction of Sonographic Placement of IVs by RNs in the Emergency Department): The Learning Curve for Peripheral IV Placement SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 [Liteplo, A. S.; Noble, V. E.; Marill, K. A.; Dipre, M.; Huang, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S32 EP S32 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500080 ER PT J AU Liu, SW Milne, LW Yun, BJ Walsh, K AF Liu, S. W. Milne, L. W. Yun, B. J. Walsh, K. TI The Boarding Experience From the Patient Perspective: The Wait SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S49 EP S50 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500129 ER PT J AU Milling, TJ Refaai, MA Goldstein, JN Goldberg-Alberts, R Schneider, A Hug, B Sarode, R AF Milling, T. J., Jr. Refaai, M. A. Goldstein, J. N. Goldberg-Alberts, R. Schneider, A. Hug, B. Sarode, R. TI Thrombotic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate or Plasma SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Dell Childrens Med Ctr, Univ Med Ctr Brackenridge, Austin, TX USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CSL Behring LLC, King Of Prussia, PA USA. CSL Behring GmbH, Marburg, Germany. UT Southwestern Med Ctr, Dallas, TX USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S10 EP S10 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500022 ER PT J AU Rolston, DM Runde, D Kathuria, N Drake, A Lee, J Raja, AS Shah, K Wiener, D Quaas, J AF Rolston, D. M. Runde, D. Kathuria, N. Drake, A. Lee, J. Raja, A. S. Shah, K. Wiener, D. Quaas, J. TI Changes in the Clot Burden of Pulmonary Embolism as Diagnosed by Computed Tomography Angiography over a 10-Year Period SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 St Lukes Roosevelt Hosp, New York, NY USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mt Sinai Hosp, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S24 EP S25 PG 2 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500061 ER PT J AU Schuur, JD Ronan, CE Berner, AR Benzer, TI Goldstein, JN Larson, RE Lyn, ET Michael, JA Rivera, M Raja, AS AF Schuur, J. D. Ronan, C. E. Berner, A. R. Benzer, T., I Goldstein, J. N. Larson, R. E. Lyn, E. T. Michael, J. A. Rivera, M. Raja, A. S. TI Head CT for Minor Head Injury: Appropriateness and Early Results of a Quality Improvement Intervention in 6 Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Newton Wellesley Hosp, Newton, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Faulkner Hosp, Jamaica Plain, MA USA. Salem Hosp, North Shore Med Ctr, Salem, MA USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S29 EP S29 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500073 ER PT J AU Schuur, JD Ronan, CE Berner, AR Benzer, TI Kabrhel, C Larson, RE Lyn, ET Rivera, M Ross, NG Raja, AS AF Schuur, J. D. Ronan, C. E. Berner, A. R. Benzer, T., I Kabrhel, C. Larson, R. E. Lyn, E. T. Rivera, M. Ross, N. G. Raja, A. S. TI Effect of a Diagnostic Pathway on the Appropriateness of Emergency Department Computed Tomography for Pulmonary Embolus SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 14-15, 2013 CL Seattle, WA SP Amer Coll Emergency Phys C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Newton Wellesley Hosp, Newton, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Faulkner Hosp, Jamaica Plain, MA USA. Salem Hosp, North Shore Med Ctr, Salem, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2013 VL 62 IS 4 SU S BP S19 EP S19 PG 1 WC Emergency Medicine SC Emergency Medicine GA 232PO UT WOS:000325506500048 ER PT J AU Ganesh, S Guernon, A Chalcraft, L Harton, B Smith, B Pape, TLB AF Ganesh, Shanti Guernon, Ann Chalcraft, Laura Harton, Brett Smith, Bridget Pape, Theresa Louise-Bender TI Medical Comorbidities in Disorders of Consciousness Patients and Their Association With Functional Outcomes SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Comorbidity; Consciousness disorders; Rehabilitation ID TRAUMATIC BRAIN-INJURY; VEGETATIVE STATE; HEAD-INJURY; FOLLOW-UP; RECOVERY; UNCONSCIOUSNESS; HYDROCEPHALUS; DYSAUTONOMIA; OVERACTIVITY; PREDICTION AB Objective: To identify, for patients in states of seriously impaired consciousness, comorbid conditions present during inpatient rehabilitation and their association with function at 1 year. Design: Abstracted data from a prospective cross-sectional observational study with data collection occurring January 1996 through December 2007. Setting: Four inpatient rehabilitation facilities in metropolitan areas. Participants: The study sample of 68 participants is abstracted from a database of 157 patients remaining in states of seriously impaired consciousness for at least 28 days. Interventions: Not applicable. Main Outcome Measure: One-year cognitive, motor, and total FIM score. Results: The most common medical complications during inpatient rehabilitation for the study sample are active seizures (46%), spasticity (57%), urinary tract infections (47%), and hydrocephalus with and without shunt (38%). Presence of >= 3 medical complications during inpatient rehabilitation, controlling for injury severity, is significantly (P<.05) associated with poorer total FIM and FIM motor scores 1 year after injury. The presence of hydrocephalus with and without shunt (r=-.20, -.21, -.18; P <=.15), active seizures (r=-.31, -.22, -.42), spasticity (r=-.38, -.28, -.40), and urinary tract infections (r=-.25, -.24, -.26) were significantly (P<.10) associated with total FIM, FIM cognitive, and FIM motor scores, respectively. Conclusions: Reported findings indicate that persons in states of seriously impaired consciousness with higher numbers of medical complications during inpatient rehabilitation are more likely to have lower functional levels 1-year postinjury. The findings indicate that persons with >= 3 medical complications during inpatient rehabilitation are at a higher risk for poorer functional outcomes at 1 year. It is, therefore, prudent to evaluate these patients for indications of these complications during inpatient rehabilitation. (c) 2013 by the American Congress of Rehabilitation Medicine C1 [Ganesh, Shanti; Harton, Brett; Smith, Bridget; Pape, Theresa Louise-Bender] US Dept Vet Affairs, Dept Vet Affairs, Res Serv, Edward Hines Jr Vet Affairs Hosp, Hines, IL 60141 USA. [Ganesh, Shanti; Harton, Brett; Smith, Bridget; Pape, Theresa Louise-Bender] US Dept Vet Affairs, Ctr Management Complex Chron Care, Ctr Excellence, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Ganesh, Shanti; Chalcraft, Laura] US Dept Vet Affairs, Phys Med & Rehabil Serv, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Guernon, Ann] Marianjoy Rehabil Hosp, Wheaton, IL USA. [Smith, Bridget] Loyola Univ Chicago, Program Hlth Serv Res, Stritch Sch Med, Maywood, IL USA. [Pape, Theresa Louise-Bender] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. RP Pape, TLB (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H,Bldg 1B260, Hines, IL 60141 USA. EM Theresa.Pape@va.gov OI Pape, Theresa/0000-0001-7738-5963 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Merit [CCN 07-133] FX Supported by the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Merit (grant no. CCN 07-133). NR 33 TC 9 Z9 10 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2013 VL 94 IS 10 BP 1899 EP 1907 DI 10.1016/j.apmr.2012.12.026 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 231TU UT WOS:000325442100008 PM 23735521 ER PT J AU Wecht, JM Rosado-Rivera, D Weir, JP Ivan, A Yen, C Bauman, WA AF Wecht, Jill M. Rosado-Rivera, Dwindally Weir, Joseph P. Ivan, Adrian Yen, Christina Bauman, William A. TI Hemodynamic Effects of L-Threo-3,4-Dihydroxyphenylserine (Droxidopa) in Hypotensive Individuals With Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Blood pressure; Droxidopa; Hypotension; Orthostatic hypotension; Paraplegia; Rehabilitation; Tetraplegia ID NEUROGENIC ORTHOSTATIC HYPOTENSION; LOW BLOOD-PRESSURE; L-DIHYDROXYPHENYLSERINE DROXIDOPA; L-THREO-DOPS; COGNITIVE PERFORMANCE; AUTONOMIC FAILURE; TETRAPLEGIC MAN; PREVALENCE; MANAGEMENT; MIDODRINE AB Objectives: To determine the effect of an escalating dose of droxidopa (100, 200, and 400mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting. Design: Open-label dose titration trial. Setting: A Veterans Administration Medical Center. Participants: Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation. Interventions: Placebo on visit 1, droxidopa 100mg on visit 2, droxidopa 200mg on visit 3, and droxidopa 400mg on visit 4. Main Outcome Measures: BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting. Results: Seated BP was significantly elevated with 400mg droxidopa compared with placebo and 100mg droxidopa for 3 hours and was elevated for 2 hours compared with 200mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400mg. There were no significant differences in the heart rate response or AE reporting among the study visits. Conclusions: Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI. (c) 2013 by the American Congress of Rehabilitation Medicine C1 [Wecht, Jill M.; Rosado-Rivera, Dwindally; Ivan, Adrian; Yen, Christina; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence, Bronx, NY 10468 USA. [Wecht, Jill M.; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Weir, Joseph P.] Univ Kansas, Dept Hlth Sport & Exercise Sci, Lawrence, KS 66045 USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rm 7A-13,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM JM.Wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [B2648C] FX Supported by the Veterans Affairs Rehabilitation Research and Development Service (grant no. B2648C). NR 33 TC 3 Z9 3 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2013 VL 94 IS 10 BP 2006 EP 2012 DI 10.1016/j.apmr.2013.03.028 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 231TU UT WOS:000325442100020 PM 23602882 ER PT J AU Stein, NR Schorr, Y Litz, BT King, LA King, DW Solomon, Z Horesh, D AF Stein, Nathan R. Schorr, Yonit Litz, Brett T. King, Lynda A. King, Daniel W. Solomon, Zahava Horesh, Danny TI Development and Validation of the Coping With Terror Scale SO ASSESSMENT LA English DT Article DE terrorism; stress; coping; scale; measurement; mental health ID MENTAL-HEALTH SYMPTOMS; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL REACTIONS; EXPOSURE; ISRAEL; THREAT; ADJUSTMENT; STRATEGIES; ADOLESCENTS; DISTRESS AB Terrorism creates lingering anxiety about future attacks. In prior terror research, the conceptualization and measurement of coping behaviors were constrained by the use of existing coping scales that index reactions to daily hassles and demands. The authors created and validated the Coping with Terror Scale to fill the measurement gap. The authors emphasized content validity, leveraging the knowledge of terror experts and groups of Israelis. A multistep approach involved construct definition and item generation, trimming and refining the measure, exploring the factor structure underlying item responses, and garnering evidence for reliability and validity. The final scale comprised six factors that were generally consistent with the authors' original construct specifications. Scores on items linked to these factors demonstrate good reliability and validity. Future studies using the Coping with Terror Scale with other populations facing terrorist threats are needed to test its ability to predict resilience, functional impairment, and psychological distress. C1 [Stein, Nathan R.; Schorr, Yonit; Litz, Brett T.; King, Lynda A.; King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Stein, Nathan R.; Schorr, Yonit; Litz, Brett T.; King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Solomon, Zahava; Horesh, Danny] Tel Aviv Univ, Bob Shappel Sch Social Work, IL-69978 Tel Aviv, Israel. RP Stein, NR (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 116B-4, Boston, MA 02130 USA. EM nathan.stein@va.gov OI Horesh, Danny/0000-0003-3574-4301 FU NIMH NIH HHS [R21 MH074501] NR 50 TC 2 Z9 2 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 EI 1552-3489 J9 ASSESSMENT JI Assessment PD OCT PY 2013 VL 20 IS 5 BP 597 EP 609 DI 10.1177/1073191111411668 PG 13 WC Psychology, Clinical SC Psychology GA 220YV UT WOS:000324624400008 PM 21676998 ER PT J AU Chibebe, J Sabino, CP Tan, XJ Junqueira, JC Wang, Y Fuchs, BB Jorge, AOC Tegos, GP Hamblin, MR Mylonakis, E AF Chibebe Junior, Jose Sabino, Caetano P. Tan, Xiaojiang Junqueira, Juliana C. Wang, Yan Fuchs, Beth B. Jorge, Antonio O. C. Tegos, George P. Hamblin, Michael R. Mylonakis, Eleftherios TI Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella SO BMC MICROBIOLOGY LA English DT Article DE Candida albicans; Photodynamic therapy; Galleria mellonella ID OXIDATIVE STRESS-RESPONSE; PHOTODYNAMIC THERAPY; CRYPTOCOCCUS-NEOFORMANS; ENTEROCOCCUS-FAECALIS; EPITHELIAL-CELLS; ORAL CANDIDOSIS; VIRULENCE; MICE; PATHOGENESIS; DISEASE AB Background: Candida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella. Results: We verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone. Conclusions: G. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains. C1 [Chibebe Junior, Jose; Junqueira, Juliana C.; Jorge, Antonio O. C.] Univ Estadual Paulista UNESP, Dept Biosci & Oral Diag, BR-12245000 Sao Jose Dos Campos, SP, Brazil. [Chibebe Junior, Jose; Tan, Xiaojiang; Wang, Yan; Fuchs, Beth B.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chibebe Junior, Jose] Fac Pindamonhangaba, Dept Restorat Dent, BR-12422970 Pindamonhangaba, SP, Brazil. [Sabino, Caetano P.; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sabino, Caetano P.] Nucl & Energy Res Inst, Ctr Lasers & Applicat, BR-05508000 Sao Paulo, Brazil. [Tan, Xiaojiang] Southern Med Univ, Huiqiao Dept, Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China. [Wang, Yan] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China. [Tegos, George P.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Mylonakis, Eleftherios] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Providence, RI 02903 USA. [Mylonakis, Eleftherios] Brown Univ, Warren Alpert Med Sch, Miriam Hosp, Providence, RI 02903 USA. RP Junqueira, JC (reprint author), Univ Estadual Paulista UNESP, Dept Biosci & Oral Diag, BR-12245000 Sao Jose Dos Campos, SP, Brazil. EM julianacjunqueira@hotmail.com RI Junqueira, Juliana/F-7785-2012; Sabino, Caetano/K-8356-2013; Sabino, Caetano/D-4196-2016; OI Sabino, Caetano/0000-0002-2048-2823; Hamblin, Michael/0000-0001-6431-4605 FU CAPES [PDEE 2507-11-0]; Science and Technology Planning Project of Guangdong Province, P.R. China [2011B080701091]; Sao Paulo Council of Research - FAPESP, Brazil [12/19915-6]; NIH [RO1 AI050875, 5U54MH084690-02]; US Air Force MFEL Program [FA9550-04-1-0079] FX Jose Chibebe Junior thanks CAPES (PDEE 2507-11-0) for the scholarship during the PhD Program at Harvard Medical School. Xiaojiang Tan was supported by Science and Technology Planning Project of Guangdong Province, P.R. China (2011B080701091). Juliana C Junqueira thanks Sao Paulo Council of Research - FAPESP, Brazil (grant 12/19915-6). Research conducted in the Mylonakis Laboratory was supported by NIH (RO1 AI050875 to EM). Research conducted in the Hamblin Laboratory was supported by NIH (RO1 AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079). George P Tegos was supported by the NIH (grant 5U54MH084690-02). NR 48 TC 10 Z9 10 U1 1 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD OCT 1 PY 2013 VL 13 AR 217 DI 10.1186/1471-2180-13-217 PG 9 WC Microbiology SC Microbiology GA 235CR UT WOS:000325693400001 PM 24083556 ER PT J AU Trowbridge, RL Dhaliwal, G Cosby, KS AF Trowbridge, Robert L. Dhaliwal, Gurpreet Cosby, Karen S. TI Educational agenda for diagnostic error reduction SO BMJ QUALITY & SAFETY LA English DT Review DE Diagnostic errors; Medical education; Cognitive biases ID COGNITIVE FORCING STRATEGIES; CLINICAL DECISION-MAKING; PATIENT SAFETY; MORTALITY CONFERENCES; MEDICAL ERRORS; MORBIDITY; INTERVENTIONS; PERCEPTIONS; PERFORMANCE; IMPROVEMENT AB Diagnostic errors are a major patient safety concern. Although the majority of diagnostic errors are partially attributable to cognitive mistakes, the most effective means of improving clinician cognition in order to achieve gains in diagnostic reliability are unclear. We propose a tripartite educational agenda for improving diagnostic performance among students, residents and practising physicians. This agenda includes strengthening the metacognitive abilities of clinicians, fostering intuitive reasoning and increasing awareness of the role of systems in the diagnostic process. The evidence supporting initiatives in each of these realms is reviewed and a course of future implementation and study is proposed. The barriers to designing and implementing this agenda are substantial and include limited evidence supporting these initiatives and the challenges of changing the practice patterns of practising physicians. Implementation will need to be accompanied by rigorous evaluation. C1 [Trowbridge, Robert L.] Maine Med Ctr, Dept Med, Portland, ME 04012 USA. [Trowbridge, Robert L.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Dhaliwal, Gurpreet] San Francisco Vet Adm Med Ctr, Med Serv, San Francisco, CA USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Cosby, Karen S.] Cook Cty Med Ctr, Dept Emergency Med, Chicago, IL USA. [Cosby, Karen S.] Rush Med Coll, Dept Emergency Med, Chicago, IL 60612 USA. RP Trowbridge, RL (reprint author), Maine Med Ctr, Dept Med, 22 Bramhall St, Portland, ME 04012 USA. EM trowbr@mmc.org NR 57 TC 1 Z9 1 U1 2 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD OCT PY 2013 VL 22 SU 2 BP ii28 EP ii32 DI 10.1136/bmjqs-2012-001622 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 222NC UT WOS:000324736900005 PM 23764435 ER PT J AU Rose, S Shapiro, G AF Rose, Suzanne Shapiro, Geoffrey TI Q&A: Geoffrey Shapiro on Phase I Drug Trials SO CANCER DISCOVERY LA English DT Editorial Material C1 [Shapiro, Geoffrey] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 OCT PY 2013 VL 3 IS 10 BP 1089 EP 1089 DI 10.1158/2159-8290.CD-ND2013-021 PG 1 WC Oncology SC Oncology GA 235WH UT WOS:000325751600005 ER PT J AU Karreth, FA Pandolfi, PP AF Karreth, Florian A. Pandolfi, Pier Paolo TI ceRNA Cross-Talk in Cancer: When ce-bling Rivalries Go Awry SO CANCER DISCOVERY LA English DT Review ID 3' UNTRANSLATED REGIONS; LONG-NONCODING-RNA; MESSENGER-RNAS; MICRORNA SPONGES; HEPATOCELLULAR-CARCINOMA; TUMOR SUPPRESSION; ENDOGENOUS RNA; CIRCULAR RNAS; HUMAN-CELLS; PTEN AB The cancer transcriptome is characterized by aberrant expression of both protein-coding and noncoding transcripts. Similar to mRNAs, a significant portion of the noncoding transcriptome, including long noncoding RNAs and pseudogenes, harbors microRNA (miRNA)-response elements (MRE). The recent discovery of competitive endogenous RNAs (ceRNA), natural decoys that compete for a common pool of miRNAs, provides a framework to systematically functionalize MRE-harboring noncoding RNAs and integrate them with the protein-coding RNA dimension in complex ceRNA networks. Functional interactions in ceRNA networks aid in coordinating a number of biologic processes and, when perturbed, contribute to disease pathogenesis. In this review, we discuss recent discoveries that implicate natural miRNA decoys in the development of cancer. Significance: Cross-talk between ceRNAs through shared miRNAs represents a novel layer of gene regulation that plays important roles in the physiology and development of diseases such as cancer. As cross-talk can be predicted on the basis of the overlap of miRNA-binding sites, we are now one step closer to a complete functionalization of the human transcriptome, especially the noncoding space. (C) 2013 AACR. C1 [Karreth, Florian A.; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med & Pathol, Canc Genet Program,Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu FU Department of Defense Prostate Cancer Research Program fellowship [W81XWH-12-1-0033]; NIH [R01 CA170158-01] FX F.A. Karreth was supported by a Department of Defense Prostate Cancer Research Program fellowship (W81XWH-12-1-0033). P.P. Pandolfi was supported by NIH grant R01 CA170158-01. NR 57 TC 70 Z9 76 U1 5 U2 36 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 OCT PY 2013 VL 3 IS 10 BP 1113 EP 1121 DI 10.1158/2159-8290.CD-13-0202 PG 9 WC Oncology SC Oncology GA 235WH UT WOS:000325751600022 PM 24072616 ER PT J AU Eisinger-Mathason, TSK Zhang, MS Qiu, Q Skuli, N Nakazawa, MS Karakasheva, T Mucaj, V Shay, JES Stangenberg, L Sadri, N Pure, E Yoon, SS Kirsch, DG Simon, MC AF Eisinger-Mathason, T. S. Karin Zhang, Minsi Qiu, Qiong Skuli, Nicolas Nakazawa, Michael S. Karakasheva, Tatiana Mucaj, Vera Shay, Jessica E. S. Stangenberg, Lars Sadri, Navid Pure, Ellen Yoon, Sam S. Kirsch, David G. Simon, M. Celeste TI Hypoxia-Dependent Modification of Collagen Networks Promotes Sarcoma Metastasis SO CANCER DISCOVERY LA English DT Article ID SOFT-TISSUE SARCOMA; UNDIFFERENTIATED PLEOMORPHIC SARCOMA; GENE-EXPRESSION; MOUSE MODEL; EXTRACELLULAR-MATRIX; LYSYL OXIDASE; GROWTH-FACTOR; CANCER; MUTATIONS; CELLS AB Intratumoral hypoxia and expression of hypoxia-inducible factor-1 alpha(HIF-1 alpha) correlate with metastasis and poor survival in patients with sarcoma. We show here that hypoxia controls sarcoma metastasis through a novel mechanism wherein HIF-1 alpha enhances expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). We show that loss of HIF-1 alpha or PLOD2 expression disrupts collagen modifi cation, cell migration, and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSL-Kras(G12D/+); Trp53(ft/ft) murine sarcoma models. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF-1 alpha-deficient tumors, and analysis of human sarcomas reveals elevated HIF1A and PLOD2 expression in metastatic primary lesions. Pharmacologic inhibition of PLOD enzymatic activity suppresses metastases. Collectively, these data indicate that HIF-1 alpha controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors. We conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination. SIGNIFICANCE: Undifferentiated pleomorphic sarcoma (UPS) is a commonly diagnosed and particularly aggressive sarcoma subtype in adults, which frequently and fatally metastasizes to the lung. Here, we show the potential use of a novel therapeutic target for the treatment of metastatic UPS, specifi cally the collagen-modifying enzyme PLOD2. (c) 2013 AACR. C1 [Eisinger-Mathason, T. S. Karin; Skuli, Nicolas; Nakazawa, Michael S.; Karakasheva, Tatiana; Mucaj, Vera; Shay, Jessica E. S.; Simon, M. Celeste] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Eisinger-Mathason, T. S. Karin; Skuli, Nicolas; Nakazawa, Michael S.; Karakasheva, Tatiana; Mucaj, Vera; Shay, Jessica E. S.; Sadri, Navid; Simon, M. Celeste] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pure, Ellen] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Zhang, Minsi; Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. [Qiu, Qiong; Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Skuli, Nicolas; Simon, M. Celeste] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Stangenberg, Lars] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yoon, Sam S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Simon, MC (reprint author), Univ Penn, Abramson Family Canc Res Inst, 456 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM celeste2@mail.med.upenn.edu FU U.S. National Cancer Institute [F32CA156979, T32CA09140, R01CA158301, R01CA138265]; Howard Hughes Medical Institute FX This work was supported by the U.S. National Cancer Institute grants F32CA156979, T32CA09140 (to T.S.K. Eisinger-Mathason), R01CA158301 (to T.S.K. Eisinger-Mathason, M.S. Nakazawa, T. Karakasheva, V. Mucaj, J.E.S. Shay, S.S. Yoon, M.C. Simon, L. Stangenberg, and E. Pure), and R01CA138265 (to D.G. Kirsch, Q. Qiu, and M. Zhang), and the Howard Hughes Medical Institute (to M.C. Simon and N. Sadri). M.C. Simon is an investigator of the Howard Hughes Medical Institute. NR 48 TC 44 Z9 46 U1 4 U2 19 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 OCT PY 2013 VL 3 IS 10 BP 1190 EP 1205 DI 10.1158/2159-8290.CD-13-0118 PG 16 WC Oncology SC Oncology GA 235WH UT WOS:000325751600028 PM 23906982 ER PT J AU Meilleur, A Subramanian, SV Plascak, JJ Fisher, JL Paskett, ED Lamont, EB AF Meilleur, Ashley Subramanian, S. V. Plascak, Jesse J. Fisher, James L. Paskett, Electra D. Lamont, Elizabeth B. TI Rural Residence and Cancer Outcomes in the United States: Issues and Challenges SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID BREAST-CANCER; MEDICARE BENEFICIARIES; PROSTATE-CANCER; SOCIOECONOMIC-STATUS; EXAMINING TRENDS; TRAVEL DISTANCE; AREA VARIATIONS; NONRURAL AREAS; LUNG-CANCER; HEALTH-CARE AB "Neighborhoods and health" research has shown that area social factors are associated with the health outcomes that patients with cancer experience across the cancer control continuum. To date, most of this research has been focused on the attributes of urban areas that are associated with residents' poor cancer outcomes with less focused on attributes of rural areas that may be associated with the same. Perhaps because there is not yet a consensus in the United States regarding how to define "rural," there is not yet an accepted analytic convention for studying issues of how patients' cancer outcomes may vary according to "rural" as a contextual attribute. The research that exists reports disparate findings and generally treats rural residence as a patient attribute rather than a contextual factor, making it difficult to understand what factors (e. g., unmeasured individual poverty, area social deprivation, area health care scarcity) may be mediating the poor outcomes associated with rural (or non-rural) residence. Here, we review literature regarding the potential importance of rural residence on cancer patients' outcomes in the United States with an eye towards identifying research conventions (i.e., spatial and analytic) that may be useful for future research in this important area. (C) 2013 AACR. C1 [Meilleur, Ashley; Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Plascak, Jesse J.; Fisher, James L.; Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Plascak, Jesse J.; Fisher, James L.; Paskett, Electra D.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Plascak, Jesse J.; Paskett, Electra D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Paskett, Electra D.] Ohio State Univ, Coll Med, Div Canc Control & Prevent, Dept Internal Med, Columbus, OH 43210 USA. RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180A Longwood Ave, Boston, MA 02115 USA. EM lamont@hcp.med.harvard.edu RI Fisher, James/F-4996-2012 FU National Institute on Aging at the National Institutes of Health [P01 AG031093] FX This study was supported by the National Institute on Aging at the National Institutes of Health (grant no. P01 AG031093). NR 66 TC 23 Z9 23 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2013 VL 22 IS 10 BP 1657 EP 1667 DI 10.1158/1055-9965.EPI-13-0404 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 234GT UT WOS:000325631200002 PM 24097195 ER PT J AU Cope, EL Shrubsole, MJ Cohen, SS Cai, QY Wu, J Ueland, PM Midttun, O Sonderman, JS Blot, WJ Signorello, LB AF Cope, Elizabeth L. Shrubsole, Martha J. Cohen, Sarah S. Cai, Qiuyin Wu, Jie Ueland, Per Magne Midttun, Oivind Sonderman, Jennifer S. Blot, William J. Signorello, Lisa B. TI Intraindividual Variation in One-Carbon Metabolism Plasma Biomarkers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER RISK; B-VITAMIN STATUS; MICROBIOLOGICAL ASSAY; TOTAL HOMOCYSTEINE; MASS-SPECTROMETRY; TERM VARIABILITY; FOLATE; CARCINOGENESIS; COHORTS; HEALTH AB Interest in the relationship between one-carbon metabolism (OCM) and carcinogenesis is intensifying, leading to increased use of related biomarkers as measures of exposure. Little is known, however, about the intraindividual variation in these markers and whether or not the use of a single measure is appropriate for assessing exposure-disease relationships in epidemiologic studies. We evaluated the intraindividual variation in plasma concentrations of 19 OCM biomarkers in a sample of 147 African American and 68 non-Hispanic white participants from the Southern Community Cohort Study who donated blood samples and responded to questionnaires at two time points from 2005 to 2008. Weighted kappa coefficients (kappa) were calculated to assess the agreement between quartile assignments based on the repeated measures. Adjusted intraclass correlation coefficients (ICC) were also used to assess the consistency of the two measurements. Most (16/19) OCM biomarkers showed a moderate or better agreement for quartile assignment at the two time points, with only methionine, methionine sulfoxide, and cystathionine having kappa <= 0.40. The median-adjusted ICC across the 19 biomarkers was 0.60. Reproducibility was highest for flavin mononucleotide [ICC = 0.84, 95% confidence interval (CI), 0.79-0.87] and lowest for methionine and its oxidative product methionine sulfoxide (ICC = 0.22, 95% CI 0.09-0.34; ICC = 0.20, 95% CI 0.07-0.32, respectively). Overall, the intraindividual variation in OCM biomarkers was similar for African Americans and whites and for males and females. Our results suggest that with the exception of methionine and methionine sulfoxide, OCM biomarkers generally have good intraindividual reproducibility and can be considered as reliable exposure measures in epidemiologic studies. (c) 2013 AACR. C1 [Cope, Elizabeth L.; Cohen, Sarah S.; Sonderman, Jennifer S.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [Shrubsole, Martha J.; Cai, Qiuyin; Wu, Jie; Blot, William J.] Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN USA. [Shrubsole, Martha J.; Cai, Qiuyin; Blot, William J.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [Ueland, Per Magne] Univ Bergen, Inst Med, Pharmacol Sect, Bergen, Norway. [Ueland, Per Magne] Haukeland Hosp, Lab Clin Biochem, N-5021 Bergen, Norway. [Midttun, Oivind] BEVITAL, Bergen, Norway. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Signorello, LB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM Signorello@hsph.harvard.edu RI Ueland, Per/C-7340-2013; Shrubsole, Martha/K-5052-2015 OI Shrubsole, Martha/0000-0002-5591-7575 FU NIH/National Cancer Institute [R01 CA092447]; Vanderbilt-Ingram Cancer Center [P30CA068485] FX The SCCS is funded by grant number R01 CA092447 from the NIH/National Cancer Institute. Sample preparation was conducted at the Survey and Biospecimen Shared Resource that is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485). NR 25 TC 6 Z9 6 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2013 VL 22 IS 10 BP 1894 EP 1899 DI 10.1158/1055-9965.EPI-13-0420 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 234GT UT WOS:000325631200028 PM 23950212 ER PT J AU Dawson, DW Hertzer, K Moro, A Donald, G Chang, HH Go, VL Pandol, SJ Lugea, A Gukovskaya, AS Li, G Hines, OJ Rozengurt, E Eibl, G AF Dawson, David W. Hertzer, Kathleen Moro, Aune Donald, Graham Chang, Hui-Hua Go, Vay Liang Pandol, Steven J. Lugea, Aurelia Gukovskaya, Anna S. Li, Gang Hines, Oscar J. Rozengurt, Enrique Eibl, Guido TI High-Fat, High-Calorie Diet Promotes Early Pancreatic Neoplasia in the Conditional Kras(G12D) Mouse Model SO CANCER PREVENTION RESEARCH LA English DT Article ID BODY-MASS INDEX; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; RISK-FACTORS; CANCER; MICE; CARCINOGENESIS; INFLAMMATION; ENHANCEMENT; PROGRESSION AB There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet- induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, for example, weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a high-fat, highcalorie diet (HFCD; similar to 4,535 kcal/kg; 40% of calories from fats) or control diet (similar to 3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared with control animals, mice fed with the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin- like growth factor I (IGF-I). The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results show that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemopreventive strategies targeting obesity-associated pancreatic cancer development. (C)2013 AACR. C1 [Dawson, David W.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Hertzer, Kathleen; Moro, Aune; Donald, Graham; Chang, Hui-Hua; Hines, Oscar J.; Eibl, Guido] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Dept Surg, Los Angeles, CA 90095 USA. [Go, Vay Liang; Pandol, Steven J.; Lugea, Aurelia; Gukovskaya, Anna S.; Rozengurt, Enrique] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Dept Med, Los Angeles, CA 90095 USA. [Li, Gang] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Dawson, David W.; Li, Gang; Hines, Oscar J.; Rozengurt, Enrique; Eibl, Guido] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Pandol, Steven J.; Lugea, Aurelia; Gukovskaya, Anna S.] Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Med, Los Angeles, CA USA. [Pandol, Steven J.] Cedars Sinai Med Ctr, Dept Internal Med, Los Angeles, CA 90048 USA. RP Eibl, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeConte Ave,72-236 CHS, Los Angeles, CA 90095 USA. EM Geibl@mednet.ucla.edu RI Dawson, David/I-5917-2014 FU NIH [P01 CA163200, P01 AT003960, R01 CA122042, P30DK41301]; Department of Veterans Affairs; Hirshberg Foundation for Pancreatic Cancer Research FX This work was supported by NIH ( P01 CA163200, P01 AT003960, R01 CA122042, P30DK41301), Department of Veterans Affairs, and Hirshberg Foundation for Pancreatic Cancer Research. NR 40 TC 28 Z9 28 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2013 VL 6 IS 10 BP 1064 EP 1073 DI 10.1158/1940-6207.CAPR-13-0065 PG 10 WC Oncology SC Oncology GA 229NE UT WOS:000325272400008 PM 23943783 ER PT J AU Travis, KE Leonard, MK Chan, AM Torres, C Sizemore, ML Qu, Z Eskandar, E Dale, AM Elman, JL Cash, SS Halgren, E AF Travis, Katherine E. Leonard, Matthew K. Chan, Alexander M. Torres, Christina Sizemore, Marisa L. Qu, Zhe Eskandar, Emad Dale, Anders M. Elman, Jeffrey L. Cash, Sydney S. Halgren, Eric TI Independence of Early Speech Processing from Word Meaning SO CEREBRAL CORTEX LA English DT Article DE ECoG; MEG; N400; speech processing ID ANTEROVENTRAL TEMPORAL-LOBE; DEPTH-RECORDED POTENTIALS; SPATIOTEMPORAL DYNAMICS; FUSIFORM GYRUS; FORM AREA; PERCEPTION; RECOGNITION; EEG; MEG; SOUNDS AB We combined magnetoencephalography (MEG) with magnetic resonance imaging and electrocorticography to separate in anatomy and latency 2 fundamental stages underlying speech comprehension. The first acoustic- phonetic stage is selective for words relative to control stimuli individually matched on acoustic properties. It begins similar to 60 ms after stimulus onset and is localized to middle superior temporal cortex. It was replicated in another experiment, but is strongly dissociated from the response to tones in the same subjects. Within the same task, semantic priming of the same words by a related picture modulates cortical processing in a broader network, but this does not begin until similar to 217 ms. The earlier onset of acoustic- phonetic processing compared with lexicosemantic modulation was significant in each individual subject. The MEG source estimates were confirmed with intracranial local field potential and high gamma power responses acquired in 2 additional subjects performing the same task. These recordings further identified sites within superior temporal cortex that responded only to the acoustic- phonetic contrast at short latencies, or the lexicosemantic at long. The independence of the early acoustic- phonetic response from semantic context suggests a limited role for lexical feedback in early speech perception. C1 [Travis, Katherine E.; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, San Diego State Univ, Dept Neurosci, San Diego, CA 92093 USA. [Leonard, Matthew K.; Elman, Jeffrey L.] Univ Calif San Diego, San Diego State Univ, Dept Cognit Sci, San Diego, CA 92093 USA. [Torres, Christina; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, San Diego State Univ, Dept Radiol, San Diego, CA 92093 USA. [Elman, Jeffrey L.; Halgren, Eric] Univ Calif San Diego, San Diego State Univ, Kavli Inst Brain & Mind, San Diego, CA 92093 USA. [Sizemore, Marisa L.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Language & Commun Disorder, San Diego, CA 92093 USA. [Chan, Alexander M.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Travis, Katherine E.; Leonard, Matthew K.; Torres, Christina; Qu, Zhe; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92037 USA. [Chan, Alexander M.; Cash, Sydney S.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Qu, Zhe] Sun Yat Sen Univ, Dept Psychol, Guangzhou 510275, Guangdong, Peoples R China. RP Halgren, E (reprint author), Univ Calif San Diego, Multimodal Imaging Lab, 8950 Villa La Jolla Dr, San Diego, CA 92037 USA. EM mkleonard@ucsd.edu; ehalgren@ucsd.edu OI Elman, Jeffrey/0000-0002-8072-2294 FU Kavli Institute for Brain and Mind; NIH [R01 NS018741, DC000041, MH020002, R01-DC005650]; NSF [BCS-0924539]; UCSD FX This study was supported by the Kavli Institute for Brain and Mind, NIH R01 NS018741, and NSF BCS-0924539. K.E.T. and M.K.L. have been supported by NIH pre-doctoral training grants DC000041 and MH020002 and the Chancellor's Collaboratories Award, UCSD. J.L. Evans supported the development of stimuli with funding from NIH R01-DC005650. NR 57 TC 11 Z9 11 U1 2 U2 17 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 OCT PY 2013 VL 23 IS 10 BP 2370 EP 2379 DI 10.1093/cercor/bhs228 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 235YT UT WOS:000325760200009 PM 22875868 ER PT J AU Graewe, B Lemos, R Ferreira, C Santana, I Farivar, R De Weerd, P Castelo-Branco, M AF Graewe, Britta Lemos, Raquel Ferreira, Carlos Santana, Isabel Farivar, Reza De Weerd, Peter Castelo-Branco, Miguel TI Impaired Processing of 3D Motion-Defined Faces in Mild Cognitive Impairment and Healthy Aging: An fMRI Study SO CEREBRAL CORTEX LA English DT Article DE face perception; functional neuroimaging; mild cognitive impairment; structure-from-motion; vision ID VOXEL-BASED MORPHOMETRY; STRUCTURE-FROM-MOTION; ALZHEIMERS-DISEASE; OBJECT RECOGNITION; LEWY BODIES; PERCEPTION; ATTENTION; TASK; CONNECTIONS; SELECTIVITY AB Mild cognitive impairment (MCI), which shows high risk for conversion to Alzheimer's disease (AD), is accompanied by progressive visual deteriorations that so far are poorly understood. Here, we compared dorsal and ventral visual stream functional magnetic resonance imaging (fMRI) activity among amnestic MCI, healthy elderly, and young participants during structure-from-motion (SFM) face categorization performance. Task performance varied with stimulus depth and duration levels and differences among groups were highly correlated with face-related fMRI activation patterns. Young participants showed larger activation to faces than scrambled faces (face sensitivity) in the right fusiform face area (FFA) and right occipital face area (OFA) whereas in elderly, this difference was reduced. Surprisingly, in MCI, scrambled faces elicited larger activation in right FFA/OFA than faces. The latter observation may be related to the additional finding of elevated depth sensitivity in left FFA/OFA of MCI, suggesting that an increased representation of low-level stimulus aspects may impair face perception in MCI. Discriminant function analysis using face and depth sensitivity indices in FFA/OFA classified MCI and healthy elderly with 88.2% accuracy, marking a fundamental distinction between groups. Potentially related findings include altered activation patterns in dorsal-ventral stream integration regions and attention-related networks of MCI patients. Our results highlight aberrant visual and additional potentially compensatory processes that identify dispositions of (preclinical) AD. C1 [Graewe, Britta; De Weerd, Peter] Maastricht Univ, Dept Cognit Neurosci, Fac Psychol & Neurosci, NL-6200 MD Maastricht, Netherlands. [Graewe, Britta; Lemos, Raquel; Ferreira, Carlos; Castelo-Branco, Miguel] Univ Coimbra, Visual Neurosci Lab, IBILI, Fac Med, P-3000548 Coimbra, Portugal. [Lemos, Raquel; Santana, Isabel] Coimbra Univ Hosp, Dept Neurol, P-3000075 Coimbra, Portugal. [Farivar, Reza] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [De Weerd, Peter] Radboud Univ Nijmegen, Donders Inst Brain Behav & Cognit, NL-6525 ED Nijmegen, Netherlands. RP Graewe, B (reprint author), Maastricht Univ, Dept Cognit Neurosci, Fac Psychol & Neurosci, POB 616, NL-6200 MD Maastricht, Netherlands. EM britta.graewe@maastrichtuniversity.nl RI Cipriano Ferreira, Carlos Daniel/K-6094-2014; OI Cipriano Ferreira, Carlos Daniel/0000-0002-0629-7146; Santana, Isabel/0000-0002-8114-9434; Castelo-Branco, Miguel/0000-0003-4364-6373; Lemos, Raquel/0000-0003-1221-915X FU Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/37385/2007, SFRH/BD/74070/2010, PTDC/SAU/NEU/68483/2006, PIC/IC/82986/2007, PIC/IC/83206/2007]; Faculty of Psychology and Neuroscience; Maastricht University FX This work was supported by the Fundacao para a Ciencia e a Tecnologia, Portugal (SFRH/BD/37385/2007 to B.G. (britta. graewe@ maastrichtuniversity.nl), SFRH/BD/74070/2010 to R. L., PTDC/SAU/NEU/68483/2006, PIC/IC/82986/2007 to M.C.B., PIC/IC/83206/2007 to I.S.) and funding from the Faculty of Psychology and Neuroscience, Maastricht University to P.D.W. NR 60 TC 10 Z9 10 U1 0 U2 23 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 OCT PY 2013 VL 23 IS 10 BP 2489 EP 2499 DI 10.1093/cercor/bhs246 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 235YT UT WOS:000325760200020 PM 22879351 ER PT J AU Abou Tayoun, AN Tunkey, CD Pugh, TJ Ross, T Shah, M Lee, CC Harkins, TT Wells, WA Tafe, LJ Amos, CI Tsongalis, GJ AF Abou Tayoun, Ahmad N. Tunkey, Christopher D. Pugh, Trevor J. Ross, Tristen Shah, Minita Lee, Clarence C. Harkins, Timothy T. Wells, Wendy A. Tafe, Laura J. Amos, Christopher I. Tsongalis, Gregory J. TI A Comprehensive Assay for CFTR Mutational Analysis Using Next-Generation Sequencing SO CLINICAL CHEMISTRY LA English DT Article ID CYSTIC-FIBROSIS AB BACKGROUND: Cystic fibrosis is a life-threatening genetic disorder that has been associated with mutations in the CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] gene. Hundreds of CFTR mutations have been detected to date. Current CFTR genotyping assays target a subset of these mutations, particularly a mutation panel recommended by the American College of Medical Genetics for carrier screening of the general population. Fast sequencing of the entire coding sequence in a scalable manner could expand the detection of CFTR mutations and facilitate management of costs and turnaround times in the clinical laboratory. METHODS: We describe a proof-of-concept CFTR assay that uses PCR target enrichment and next-generation sequencing on the Ion Torrent Personal Genome Machine (TM) (PGM (TM)) platform. RESULTS: The scalability of the assay was demonstrated, with an average mean depth of coverage ranging from 500X to 3500X, depending on the number of multiplexed patient samples and the Ion Torrent chip used. In a blinded study of 79 previously genotyped patient DNA samples and cell lines, our assay detected most of the mutations, including single-nucleotide variants, small insertions and deletions, and large copy-number variants. The reproducibility was 100% for detecting mutations in independent runs. Our assay demonstrated high specificity, with only 2 false-positive calls (at 2184delA) found in 2 samples caused by a sequencing error in a homopolymer stretch of sequence. The detection rate for variants of unknown significance was very low in the targeted region. CONCLUSIONS: With continued optimization and system refinements, PGM sequencing promises to be a powerful, rapid, and scalable means of clinical diagnostic sequencing. (c) 2013 American Association for Clinical Chemistry C1 [Abou Tayoun, Ahmad N.; Tunkey, Christopher D.; Wells, Wendy A.; Tafe, Laura J.; Tsongalis, Gregory J.] Geisel Sch Med Dartmouth, Dept Pathol, Hanover, NH USA. [Abou Tayoun, Ahmad N.; Tunkey, Christopher D.; Wells, Wendy A.; Tafe, Laura J.; Amos, Christopher I.; Tsongalis, Gregory J.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. [Abou Tayoun, Ahmad N.; Tunkey, Christopher D.; Wells, Wendy A.; Tafe, Laura J.; Amos, Christopher I.; Tsongalis, Gregory J.] Norris Cotton Canc Ctr, Lebanon, NH USA. [Pugh, Trevor J.] Partners HealthCare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA. [Pugh, Trevor J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ross, Tristen; Shah, Minita; Lee, Clarence C.; Harkins, Timothy T.] Life Technol, Foster City, CA USA. [Amos, Christopher I.] Geisel Sch Med Dartmouth, Dept Community & Family Med, Ctr Genom Med, Hanover, NH USA. RP Tsongalis, GJ (reprint author), Geisel Sch Med Dartmouth, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM gregory.j.tsongalis@hitchcock.org FU NCI NIH HHS [P30 CA023108]; NIGMS NIH HHS [P20 GM103534] NR 11 TC 22 Z9 22 U1 0 U2 17 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 OCT PY 2013 VL 59 IS 10 BP 1481 EP 1488 DI 10.1373/clinchem.2013.206466 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 231FG UT WOS:000325399800012 PM 23775370 ER PT J AU Zallman, L Tendulkar, S Bhuyia, N Dube, B Early, S Arredondo, M Puleo, R Sengupta, N Alsan, B Hacker, K AF Zallman, Leah Tendulkar, Shalini Bhuyia, Nazmim Dube, Blessing Early, Scott Arredondo, Melida Puleo, Rozanne Sengupta, Nandini Alsan, Burak Hacker, Karen TI Provider's Perspectives on Building Research and Quality Improvement Capacity in Primary Care: A Strategy to Improve Workforce Satisfaction SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE translational research; evidence-based medicine; outcomes research ID HEALTH-SERVICES RESEARCH; PHYSICIANS; COMMUNITY; REFORM AB ObjectivesSafety-net populations are underrepresented in research and quality improvement (QI) studies despite the fact that safety-net providers are uniquely positioned to engage in translational research. This study aimed to understand the current level of interest in, experience with, predicted career satisfaction associated with, and barriers experienced in conducting research and QI among primary care providers (PCPs) at 18 safety-net practices in the Boston, Massachusetts area. MethodsThe Harvard Catalyst Safety-net Infrastructure Initiative partnered with staff at a large academic public hospital system, including 15 primary care sites, to develop and administer an online survey. This survey was then adapted and administered at three other academically affiliated community health centers. ResultsOf the 260 providers surveyed, 136 (52%) responded. Nearly 80% reported interest in conducting either QI projects or clinical research and 95% of them believed it would enhance their career satisfaction. However, 63% did not report prior experience or training in research or QI and 93% reported at least one barrier to engagement. ConclusionWhile supporting safety-net PCPs' engagement in research and/or QI may improve career satisfaction there are numerous barriers that must be addressed to achieve this goal. C1 [Zallman, Leah; Tendulkar, Shalini; Bhuyia, Nazmim; Dube, Blessing; Hacker, Karen] Inst Community Hlth, Cambridge, MA USA. [Zallman, Leah; Tendulkar, Shalini; Bhuyia, Nazmim; Dube, Blessing; Hacker, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Early, Scott; Puleo, Rozanne] Lynn Community Hlth Ctr, Lynn, MA USA. [Early, Scott; Puleo, Rozanne] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Arredondo, Melida; Alsan, Burak] Uphams Corner Hlth Ctr, Dorcester, MA USA. [Sengupta, Nandini] Dimock Ctr, Roxbury, MA USA. [Sengupta, Nandini] Beth Israel Deaconess Deaconess Med Ctr, Boston, MA 02215 USA. RP Zallman, L (reprint author), Inst Community Hlth, Cambridge, MA USA. EM lzallman@challiance.org FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH Award) [UL1 RR 025758]; Harvard University FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, the National Center for Research Resources, or the National Institutes of Health. NR 24 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 EI 1752-8062 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD OCT PY 2013 VL 6 IS 5 BP 404 EP 408 DI 10.1111/cts.12066 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 234IR UT WOS:000325637000014 PM 24127931 ER PT J AU Dunn, EC McLaughlin, KA Slopen, N Rosand, J Smoller, JW AF Dunn, Erin C. McLaughlin, Katie A. Slopen, Natalie Rosand, Jonathan Smoller, Jordan W. TI DEVELOPMENTAL TIMING OF CHILD MALTREATMENT AND SYMPTOMS OF DEPRESSION AND SUICIDAL IDEATION IN YOUNG ADULTHOOD: RESULTS FROM THE NATIONAL LONGITUDINAL STUDY OF ADOLESCENT HEALTH SO DEPRESSION AND ANXIETY LA English DT Article DE developmental timing; sensitive period; child maltreatment; depression; suicidal ideation ID GENDER-DIFFERENCES; NEURAL DEVELOPMENT; IMPACT; BRAIN; BEHAVIOR; OUTCOMES; ASSOCIATION; ADJUSTMENT; DISORDERS; ATTENTION AB Background Child maltreatment is a potent risk factor for psychopathology. Although the developmental timing of first exposure to maltreatment is considered important in shaping risk of future psychopathology, no consensus exists on whether earlier or later exposures are more deleterious. This study examines whether age at first exposure to abuse is associated with subsequent depression and suicidal ideation. Methods Data were drawn from the National Longitudinal Study of Adolescent Health (n = 15,701). Timing of first maltreatment exposure was classified using: (1) a crude measure capturing early childhood (ages 0-5), middle childhood (ages 6-10), or adolescence (ages 11-17); and (2) a refined measure capturing infancy (ages 0-2), preschool (ages 3-5), latency (ages 6-8), prepubertal (ages 9-10), pubertal (ages 11-13), or adolescence (ages 14-17). We examined whether timing of first exposure was associated with depression and suicidal ideation in early adulthood in the entire sample and among those exposed to maltreatment. Results Respondents exposed to abuse, particularly physical abuse, at any age had a higher odds of depression and suicidal ideation in young adulthood than nonmaltreated respondents. Among maltreated respondents, exposure during early childhood (ages 0-5), particularly preschool (ages 3-5), was most strongly associated with depression. Respondents first exposed to physical abuse during preschool had a 77% increase in the odds of depression and those first exposed to sexual abuse during early childhood had a 146% increase in the odds of suicidal ideation compared to respondents maltreated as adolescents. Conclusions Developmental timing of first exposure to maltreatment influences risk for depression and suicidal ideation. Whether these findings are evidence for biologically based sensitive periods requires further study. (C) 2013 Wiley Periodicals, Inc. C1 [Dunn, Erin C.; Rosand, Jonathan; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dunn, Erin C.; Smoller, Jordan W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dunn, Erin C.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [McLaughlin, Katie A.; Slopen, Natalie; Smoller, Jordan W.] Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Dept Psychiat, Div Gen Pediat,Boston Childrens Hosp, Boston, MA 02115 USA. [Slopen, Natalie] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Rosand, Jonathan] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St,Simches Res Bldg,6th Floor,Room, Boston, MA 02114 USA. EM erindunn@pngu.mgh.harvard.edu OI McLaughlin, Katie/0000-0002-1362-2410 FU National Institute of Health [K24MH094614] FX Contract grant sponsor: National Institute of Health; Contract grant number: K24MH094614. NR 45 TC 33 Z9 36 U1 7 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2013 VL 30 IS 10 BP 955 EP 964 DI 10.1002/da.22102 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 232GU UT WOS:000325481400010 PM 23592532 ER PT J AU Baek, JH Eisner, LR Nierenberg, AA AF Baek, Ji Hyun Eisner, Lori R. Nierenberg, Andrew A. TI SMOKING AND SUICIDALITY IN SUBJECTS WITH BIPOLAR DISORDER: RESULTS FROM THE NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED CONDITIONS (NESARC) SO DEPRESSION AND ANXIETY LA English DT Article DE bipolar disorder; mood disorder; smoking; suicide; epidemiology ID CIGARETTE-SMOKING; TOBACCO SMOKING; PERSONALITY-DISORDERS; ANXIETY DISORDERS; COMMUNITY SAMPLE; MARIJUANA USE; ASSOCIATION; PREVALENCE; RISK; COMORBIDITY AB Background Smoking in patients with bipolar disorder is known to be related to suicidality. This link has not been investigated, however, in community-based samples. The aim of this study is to delineate the sociodemographic and clinical characteristics of bipolar smokers and examine the relationship between these characteristics and suicidal ideation or attempts in an epidemiologic database, the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Methods Subjects (n = 1,643) with bipolar disorder I and II, defined by the DSM-IV criteria, who had a history of low moods lasting more than 2 weeks were included in our analysis. Current smokers, former smokers, and lifetime nonsmokers were compared in terms of demographic, clinical characteristics, and functional level. Suicidality, evaluated by a history of suicide ideation and attempts while in low mood were compared. Results Current smokers with bipolar disorder showed a greater number of DSM-IV symptoms while in acute episodes, higher rate of alcohol, and drug use disorders, as well as poorer functional levels than nonsmokers. Previous smokers displayed intermediate characteristics between current smokers and nonsmokers. The logistic regression analysis revealed that current smoking status predicted the risk of having a history of attempted suicide (Odds ratio 1.35, 95% CI: 1.05-1.76) after adjusting for age, sex, race, bipolar subtype, lifetime axis II/anxiety/alcohol use/substance use disorder; however, lifetime smoking status did not. Conclusions The present study confirms that current cigarette smoking can predict attempted suicide in a community representative sample of people with bipolar disorder. (C) 2013 Wiley Periodicals, Inc. C1 [Baek, Ji Hyun; Eisner, Lori R.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Baek, Ji Hyun; Eisner, Lori R.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Eisner, Lori R.; Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Suite 580,50 Staniford St, Boston, MA 02114 USA. EM anierenberg@partners.org NR 36 TC 8 Z9 8 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2013 VL 30 IS 10 BP 982 EP 990 DI 10.1002/da.22107 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 232GU UT WOS:000325481400013 PM 23658140 ER PT J AU Betz, ME Sullivan, AF Manton, AP Espinola, JA Miller, I Camargo, CA Boudreaux, ED AF Betz, Marian E. Sullivan, Ashley F. Manton, Anne P. Espinola, Janice A. Miller, Ivan Camargo, Carlos A., Jr. Boudreaux, Edwin D. CA ED-SAFE Investigators TI KNOWLEDGE, ATTITUDES, AND PRACTICES OF EMERGENCY DEPARTMENT PROVIDERS IN THE CARE OF SUICIDAL PATIENTS SO DEPRESSION AND ANXIETY LA English DT Article DE suicide; emergency medicine; healthcare provider ID MENTAL-HEALTH; PSYCHIATRIC EMERGENCIES; PREVENTION; RISK; MEDICINE; BEHAVIOR; NURSES; POPULATION; MANAGEMENT; PERSONNEL AB Background We sought to examine the knowledge, attitudes, and practices of emergency department (ED) providers concerning suicidal patient care and to identify characteristics associated with screening for suicidal ideation (SI). Methods Six hundred thirty-one providers at eight EDs completed a voluntary, anonymous survey (79% response rate). Results The median participant age was 35 (interquartile range: 30-44) years and 57% of the participants were females. Half (48%) were nurses and half were attending (22%) or resident (30%) physicians. More expressed confidence in SI screening skills (81-91%) than in skills to assess risk severity (64-70%), counsel patients (46-56%), or create safety plans (23-40%), with some differences between providers. Few thought mental health provider staffing was almost always sufficient (6-20%) or that suicidal patient treatment was almost always a top ED priority (15-21%). More nurses (37%, 95% confidence interval [CI] 31-42%) than physicians (7%, 95% CI 4-10%) reported screening most or all patients for SI; this difference persisted after multivariable adjustment. In multivariable analysis, other factors associated with screening most or all patients for SI were self-confidence in skills, (odds ratio [OR] 1.60, 95% CI 1.17-2.18), feeling that suicidal patient care was a top ED priority (OR 1.73, 95% CI 1.11-2.69) and 5+ postgraduate years of clinical experience (OR 2.06, 95% CI 1.03-4.13). Conclusions ED providers reported confidence in suicide screening skills but gaps in further assessment, counseling, or referral skills. Efforts to promote better identification of suicidal patients should be accompanied by a commensurate effort to improve risk assessment and management skills, along with improved access to mental health specialists. (C) 2013 Wiley Periodicals, Inc. C1 [Betz, Marian E.] Univ Colorado, Dept Emergency Med, Sch Med, Aurora, CO 80045 USA. [Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Manton, Anne P.] Cape Cod Hosp, Hyannis, MA USA. [Miller, Ivan] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Betz, ME (reprint author), Univ Colorado, Dept Emergency Med, Sch Med, 12401 E 17th Ave B-215, Aurora, CO 80045 USA. EM marian.betz@ucdenver.edu OI Betz, Marian/0000-0003-1643-6565; Boudreaux, Edwin/0000-0002-3223-6371 FU National Institute of Mental Health [U01MH088278] FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: U01MH088278. NR 31 TC 15 Z9 15 U1 2 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2013 VL 30 IS 10 BP 1005 EP 1012 DI 10.1002/da.22071 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 232GU UT WOS:000325481400016 PM 23426881 ER PT J AU Betz, ME Miller, M Barber, C Miller, I Sullivan, AF Camargo, CA Boudreaux, ED AF Betz, Marian E. Miller, Matthew Barber, Catherine Miller, Ivan Sullivan, Ashley F. Camargo, Carlos A., Jr. Boudreaux, Edwin D. CA ED-SAFE Investigators TI LETHAL MEANS RESTRICTION FOR SUICIDE PREVENTION: BELIEFS AND BEHAVIORS OF EMERGENCY DEPARTMENT PROVIDERS SO DEPRESSION AND ANXIETY LA English DT Article DE firearm; hospital care; emergency psychiatry; screening; attitudes ID MENTAL-HEALTH; RISK; EDUCATION; CARE; OPPORTUNITY; MANAGEMENT; ATTITUDES; MEDICINE AB BackgroundWe sought to examine the beliefs and behaviors of emergency department (ED) providers related to preventing suicide by reducing suicidal patients' access to lethal methods (means restriction) and identify characteristics associated with asking patients about firearm access. MethodsPhysicians and nurses at eight EDs completed a confidential, voluntary survey. ResultsThe response rate was 79% (n = 631); 57% of respondents were females and 49% were nurses. Less than half believed, most or all suicides are preventable. More nurses (67%) than physicians (44%) thought most or all firearm suicide decedents would have died by another method had a firearm been unavailable (P < .001). The proportion of providers who reported they almost always ask suicidal patients about firearm access varied across five patient scenarios: suicidal with firearm suicide plan (64%), suicidal with no suicide plan (22%), suicidal with nonfirearm plan (21%), suicidal in past month but not today (16%), and overdosed but no longer suicidal (9%). In multivariable logistic regression, physicians were more likely than nurses to almost always or often ask about a firearm across all five scenarios, as were older providers and those who believed their own provider type was responsible for assessing firearm access. ConclusionsMany ED providers are skeptical about the preventability of suicide and the effectiveness of means restriction, and most do not assess suicidal patients' firearm access except when a patient has a firearm suicide plan. These findings suggest the need for targeted staff education concerning means restriction for suicide prevention. C1 [Betz, Marian E.] Univ Colorado, Dept Emergency Med, Sch Med, Aurora, CO 80045 USA. [Miller, Matthew; Barber, Catherine] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Injury Control Res Ctr, Boston, MA 02115 USA. [Miller, Ivan] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Betz, ME (reprint author), Univ Colorado, Dept Emergency Med, Sch Med, 12401 E 17th Ave B-215, Aurora, CO 80045 USA. EM marian.betz@ucdenver.edu OI Betz, Marian/0000-0003-1643-6565; Boudreaux, Edwin/0000-0002-3223-6371 FU NIMH NIH HHS [U01 MH088278, U01MH088278] NR 36 TC 19 Z9 19 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2013 VL 30 IS 10 BP 1013 EP 1020 DI 10.1002/da.22075 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 232GU UT WOS:000325481400017 PM 23495002 ER PT J AU Gradus, JL Suvak, MK Wisco, BE Marx, BP Resick, PA AF Gradus, Jaimie L. Suvak, Michael K. Wisco, Blair E. Marx, Brian P. Resick, Patricia A. TI TREATMENT OF POSTTRAUMATIC STRESS DISORDER REDUCES SUICIDAL IDEATION SO DEPRESSION AND ANXIETY LA English DT Article DE stress disorders; posttraumatic; suicidal ideation; psychotherapy; life change events; clinical trial ID COGNITIVE-PROCESSING THERAPY; RISK-FACTORS; PROLONGED EXPOSURE; HOPELESSNESS; COMORBIDITY; DEPRESSION; PREVALENCE; VETERANS AB Background Suicide is a significant public health problem. Although various studies have found evidence of posttraumatic stress disorder (PTSD) as a risk factor for suicidal behaviors, no study has examined whether or not PTSD treatment decreases suicidal thoughts. This study aims to fill this gap in the literature by examining changes in suicidal ideation over the course of a randomized clinical trial, which compared two widely used treatments for PTSDcognitive processing therapy (CPT) and prolonged exposure (PE). Methods Data from 163 trial participants over five time points (pre- and posttreatment, 3 and 9 months posttreatment, and 5-10 years posttreatment) were examined using multilevel growth curve analyses to determine if reductions in PTSD symptoms during treatment were associated with reductions in suicidal ideation. Major depression diagnosis and hopelessness were controlled. Results Suicidal ideation decreased sharply during treatment with continued, but more subtle decreases, during the follow-up period. These decreases were associated with decreases in PTSD symptoms over the course of treatment. These associations were not accounted for by depression diagnoses at the start of the study or changes in hopelessness over the course of treatment. Conclusions Two widely used, effective treatments for PTSD reduce suicidal ideation. CPT exhibited a larger influence on suicidal ideation than PE, although the magnitude of the difference was small in size. Inclusion of PTSD screening and treatment could enhance suicide prevention efforts. C1 [Gradus, Jaimie L.; Suvak, Michael K.; Wisco, Blair E.; Marx, Brian P.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Gradus, Jaimie L.; Wisco, Blair E.; Marx, Brian P.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM Jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU National Institute of Mental Health [NIH-1 R01-MH51509] FX Contract grant sponsor: National Institute of Mental Health; contract grant number: NIH-1 R01-MH51509. NR 33 TC 20 Z9 20 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2013 VL 30 IS 10 BP 1046 EP 1053 DI 10.1002/da.22117 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 232GU UT WOS:000325481400020 PM 23636925 ER PT J AU Rubinsky, AD Bishop, MJ Maynard, C Henderson, WG Hawn, MT Harris, AHS Beste, LA Tonnesen, H Bradley, KA AF Rubinsky, Anna D. Bishop, Michael J. Maynard, Charles Henderson, William G. Hawn, Mary T. Harris, Alex H. S. Beste, Lauren A. Tonnesen, Hanne Bradley, Katharine A. TI Postoperative risks associated with alcohol screening depend on documented drinking at the time of surgery SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol; Drinking; AUDIT-C; Postoperative complications; Postoperative health care utilization ID DISORDERS IDENTIFICATION TEST; QUALITY IMPROVEMENT PROGRAM; MAJOR NONCARDIAC SURGERY; ELECTIVE SURGERY; AUDIT-C; VETERANS; CONSUMPTION; MORTALITY; PATIENT; CARE AB Background: Both AUDIT-C alcohol screening scores up to a year before surgery and clinical documentation of drinking over 2 drinks per day immediately prior to surgery ("documented drinking >2 d/d") are associated with increased postoperative complications and health care utilization. The purpose of this study was to evaluate whether documented drinking >2 d/d contributed additional information about postoperative risk beyond past-year AUDIT-C screening results. Method: Male Veterans Affairs (VA) patients who had a non-emergent, non-cardiac, major surgery assessed by the VA's Surgical Quality Improvement Program 10/2003-9/2006 and completed the AUDIT-C by mailed survey in the prior year were eligible for this study. Linear or logistic regression models compared 30-day postoperative complication(s), return to operating room (OR), hospital length of stay (LOS), and intensive care unit (ICU) days across eight groups defined by past-year AUDIT-C score and clinically documented drinking >2 d/d, with AUDIT-C scores 1-4 and no documented drinking >2 d/d as the referent, after adjusting for important covariates. Results: Overall 8811 patients met inclusion criteria. Among patients with documented drinking >2 d/d immediately prior to surgery, postoperative risk varied widely depending on past-year AUDIT-C score; scores >= 5 were associated with increased risk of complication(s), and scores >= 9 with increased hospital LOS and ICU days. Among patients without documentation of drinking >2 d/d, increasing AUDIT-C scores were not associated with these outcomes. Conclusions: Clinical documentation of drinking >2 d/d immediately prior to surgery contributed additional information about postoperative risk beyond past-year AUDIT-C score. However, among patients with documented drinking >2 d/d, postoperative risk varied widely depending on the AUDIT-C score. Published by Elsevier Ireland Ltd. C1 [Rubinsky, Anna D.; Maynard, Charles; Beste, Lauren A.; Bradley, Katharine A.] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Henderson, William G.] Dept Vet Affairs Eastern Colorado Healthcare Syst, Denver, CO USA. [Harris, Alex H. S.] Dept Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Beste, Lauren A.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Rubinsky, Anna D.; Maynard, Charles; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bishop, Michael J.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO 80045 USA. [Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35233 USA. [Tonnesen, Hanne] Bispebjerg Hosp, World Hlth Org Collaborating Ctr Evidence Based H, DK-2400 Copenhagen, Denmark. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Rubinsky, AD (reprint author), 1660 South Columbian Way S-152, Seattle, WA 98108 USA. EM Anna.Rubinsky@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development [IAC 06-021]; Agency for Healthcare Research and Quality (AHRQ) National Research Services Award (NRSA) at the University of Washington [T32 HS013853] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development (IAC 06-021). Dr. Rubinsky was also supported by an Agency for Healthcare Research and Quality (AHRQ) National Research Services Award (NRSA) at the University of Washington (T32 HS013853). The Department of Veterans Affairs and AHRQ had no further role in study design; in the analysis or interpretation of data; in the writing of this report; or in the decision to submit the paper for publication. 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, AHRQ the United States Government, or any of the authors' institutions. NR 36 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2013 VL 132 IS 3 BP 521 EP 527 DI 10.1016/j.drugalcdep.2013.03.022 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 232RC UT WOS:000325510700018 PM 23683792 ER PT J AU Schuman-Olivier, Z Hoeppner, BB Weiss, RD Borodovsky, J Shaffer, HJ Albanese, MJ AF Schuman-Olivier, Zey Hoeppner, Bettina B. Weiss, Roger D. Borodovsky, Jacob Shaffer, Howard J. Albanese, Mark J. TI Benzodiazepine use during buprenorphine treatment for opioid dependence: Clinical and safety outcomes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Buprenorphine; Opioid dependence; Benzodiazepine; Accident; Female; Utilization ID METHADONE-MAINTENANCE TREATMENT; GENDER-DIFFERENCES; PRIMARY-CARE; ABUSE; SUBSTITUTION; MORTALITY; DRUGS; PHARMACOKINETICS; TRANQUILIZERS; IMPAIRMENT AB Background: Prescribing benzodiazepines during buprenorphine treatment is a topic of active discussion. Clinical benefit is unclear. Overdose, accidental injury, and benzodiazepine misuse remain concerns. We examine the relationship between benzodiazepine misuse history, benzodiazepine prescription, and both clinical and safety outcomes during buprenorphine treatment. Methods: We retrospectively examined outpatient buprenorphine treatment records, classifying patients by past-year benzodiazepine misuse history and approved benzodiazepine prescription at intake. Primary clinical outcomes included 12-month treatment retention and urine toxicology for illicit opioids. Primary safety outcomes included total emergency department (ED) visits and odds of an ED visit related to overdose or accidental injury during treatment. Results: The 12-month treatment retention rate for the sample (N = 328) was 40%. Neither benzodiazepine misuse history nor benzodiazepine prescription was associated with treatment retention or illicit opioid use. Poisson regressions of ED visits during buprenorphine treatment revealed more ED visits among those with a benzodiazepine prescription versus those without (p < 0.001); benzodiazepine misuse history had no effect. The odds of an accidental injury-related ED visit during treatment were greater among those with a benzodiazepine prescription (OR: 3.7, p < 0.01), with an enhanced effect among females (OR: 4.7, p < 0.01). Overdose was not associated with benzodiazepine misuse history or prescription. Conclusions: We found no effect of benzodiazepine prescriptions on opioid treatment outcomes; however, benzodiazepine prescription was associated with more frequent ED visits and accidental injuries, especially among females. When prescribing benzodiazepines during buprenorphine treatment, patients need more education about accidental injury risk. Alternative treatments for anxiety should be considered when possible, especially among females. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Schuman-Olivier, Zey; Hoeppner, Bettina B.; Weiss, Roger D.; Shaffer, Howard J.; Albanese, Mark J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Schuman-Olivier, Zey; Hoeppner, Bettina B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Borodovsky, Jacob] Tufts Univ, Boston, MA 02111 USA. [Weiss, Roger D.] McLean Hosp, Belmont, MA 02178 USA. Cambridge Hlth Alliance, Cambridge, MA USA. RP Schuman-Olivier, Z (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Ctr Addict Med, Boston, MA 02114 USA. EM zschuman@partners.org OI Borodovsky, Jacob T./0000-0001-7112-5677 FU Harvard Medical School Dupont-Warren Psychiatry Research Fellowship; NIDA [K24DA022288, U10 DA15831]; NIH [UL1RR025758]; Tufts University Career Services; [K01DA027097] FX Funding for this study was provided through several sources. Dr. Schuman-Olivier conducted this research while receiving salary support through a Harvard Medical School Dupont-Warren Psychiatry Research Fellowship. Dr. Weiss supported the study with funding through NIDA Grants K24DA022288 and U10 DA15831 (RW). In her role as director of statistics at MGH Center for Addiction Medicine, Bettina Hoeppner contributed to statistical analysis while supported by K01DA027097 (BH). Use of REDCAP database services were supported by a NIH grant UL1RR025758 to Harvard Catalyst. Jacob Borodovsky received a summer research scholarship provided by Tufts University Career Services to provide support for his time. No funding sources had any role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 43 TC 11 Z9 11 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2013 VL 132 IS 3 BP 580 EP 586 DI 10.1016/j.drugalcdep.2013.04.006 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 232RC UT WOS:000325510700026 PM 23688843 ER PT J AU Condon, P Barrett, LF AF Condon, Paul Barrett, Lisa Feldman TI Conceptualizing and Experiencing Compassion SO EMOTION LA English DT Article DE emotion; subjective experience; multidimensional scaling; affective circumplex; Conceptual Act Theory ID EMOTION AB Does compassion feel pleasant or unpleasant? Westerners tend to categorize compassion as a pleasant or positive emotion, but laboratory compassion inductions, which present another's suffering, may elicit unpleasant feelings. Across two studies, we examined whether prototypical conceptualizations of compassion (as pleasant) differ from experiences of compassion (as unpleasant). After laboratory-based neutral or compassion inductions, participants made abstract judgments about compassion relative to various emotion-related adjectives, thereby providing a prototypical conceptualization of compassion. Participants also rated their own affective states, thereby indicating experiences of compassion. Conceptualizations of compassion were pleasant across neutral and compassion inductions. After exposure to others' suffering, however, participants felt increased levels of compassion and unpleasant affect, but not pleasant affect. After neutral inductions, participants reported more pleasant than unpleasant affect, with moderate levels of compassion. Thus, prototypical conceptualizations of compassion are pleasant, but experiences of compassion can feel pleasant or unpleasant. The implications for emotion theory in general are discussed. C1 [Condon, Paul; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Condon, P (reprint author), Northeastern Univ, Dept Psychol, 360 Huntington Ave, Boston, MA 02115 USA. EM condon.p@husky.neu.edu FU NCCDPHP CDC HHS [DP10D003312]; NIH HHS [DP1 OD003312] NR 21 TC 7 Z9 7 U1 2 U2 21 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 EI 1931-1516 J9 EMOTION JI Emotion PD OCT PY 2013 VL 13 IS 5 BP 817 EP 821 DI 10.1037/a0033747 PG 5 WC Psychology, Experimental SC Psychology GA 232CQ UT WOS:000325467200003 PM 23914766 ER PT J AU Moretti, E Desmedt, C Biagioni, C Regan, MM Oakman, C Larsimont, D Galardi, F Piccart-Gebhart, M Sotiriou, C Rimm, DL Di Leo, A AF Moretti, Erica Desmedt, Christine Biagioni, Chiara Regan, Meredith M. Oakman, Catherine Larsimont, Denis Galardi, Francesca Piccart-Gebhart, Martine Sotiriou, Christos Rimm, David L. Di Leo, Angelo TI TOP2A protein by quantitative immunofluorescence as a predictor of response to epirubicin in the neoadjuvant treatment of breast cancer SO FUTURE ONCOLOGY LA English DT Article DE anthracyclines; biomarker; breast cancer; quantitative immunofluorescence; TOP2A ID TOPOISOMERASE-II-ALPHA; ADJUVANT CHEMOTHERAPY; ETOPOSIDE RESISTANCE; GENE AMPLIFICATION; TISSUE MICROARRAYS; COOPERATIVE GROUP; MYELOMA CELLS; EXPRESSION; HER2; ANTHRACYCLINES AB Aim: Anthracyclines are commonly used in breast cancer, although they lack validated predictive biomarkers. We explored the interaction between TOP2A protein by quantitative immunofluorescence (QIF) and anthracycline sensitivity. Patients & methods: Patients with estrogen receptor-negative breast cancer received neoadjuvant epirubicin. Pretreatment biopsies were analyzed using AQUA((R)). Total, cytoplasmic (C) and nuclear (N) TOP2A protein concentrations were expressed as QIF scores and compared with pathologic complete response (pCR), TOP2A by immunohistochemistry, TOP2A mRNA, TOP2A and HER2 gene status, and Ki-67 level. Results: In total, 76 cases were assessable. C, N, and total scores did not correlate with pCR, or other markers. The N:C ratio differed significantly by HER2 status. No pCRs occurred in patients in the lowest N:C quartile. Conclusion: Although no relevant correlation between TOP2A QIF scores and pCR was found, N:C ratio may have a negative predictive role, and may merit further exploration in a multifactorial predictive model that includes tumor and host factors. C1 [Moretti, Erica; Biagioni, Chiara; Oakman, Catherine; Di Leo, Angelo] Hosp Prato, Sandro Pitigliani Med Oncol Unit, Ist Toscano Tumori, I-59100 Prato, Italy. [Desmedt, Christine; Sotiriou, Christos] Inst Jules Bordet, Breast Canc Translat Res Lab JC Heuson, B-1000 Brussels, Belgium. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Larsimont, Denis] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium. [Galardi, Francesca] Hosp Prato, Translat Res Unit, Ist Toscano Tumori, I-59100 Prato, Italy. [Piccart-Gebhart, Martine] Univ Libre Brussels, Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. RP Di Leo, A (reprint author), Hosp Prato, Sandro Pitigliani Med Oncol Unit, Ist Toscano Tumori, Piazza Osped 2, I-59100 Prato, Italy. EM adileo@usl4.toscana.it OI Desmedt, Christine/0000-0002-5223-5579 FU Fondation Luxembourgeoise contre le Cancer; Fonds National de la Recherche Scientifique; Brussels Region; Walloon Region (BIOWIN); European Commission through the 'Advancing Clinico-Genomic Trials' project [FP6-2005-IST-026996] FX The TOP trial was supported by the 'Fondation Luxembourgeoise contre le Cancer', the 'Fonds National de la Recherche Scientifique', the Brussels Region (Impulse Programme 2007), the Walloon Region (BIOWIN), as well as the European Commission through the 'Advancing Clinico-Genomic Trials' project (FP6-2005-IST-026996). C Desmedt and C Sotiriou are coauthors on a patent describing the A-Score. DL Rimm is a consultant to, and stockholder in HistoRx, the exclusive licensee of the Yale-held AQUA (R) patent. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 42 TC 3 Z9 4 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD OCT PY 2013 VL 9 IS 10 BP 1477 EP 1487 DI 10.2217/fon.13.103 PG 11 WC Oncology SC Oncology GA 231IT UT WOS:000325410600015 PM 24106899 ER PT J AU Qi, YP Li, XH Zhang, Y Starker, CG Baltes, NJ Zhang, F Sander, JD Reyon, D Joung, JK Voytas, DF AF Qi, Yiping Li, Xiaohong Zhang, Yong Starker, Colby G. Baltes, Nicholas J. Zhang, Feng Sander, Jeffry D. Reyon, Deepak Joung, J. Keith Voytas, Daniel F. TI Targeted Deletion and Inversion of Tandemly Arrayed Genes in Arabidopsis thaliana Using Zinc Finger Nucleases SO G3-GENES GENOMES GENETICS LA English DT Article DE zinc finger nuclease (ZFN); tandemly arrayed genes (TAGs); deletion; inversion; Arabidopsis ID DOUBLE-STRAND BREAKS; REVERSE GENETICS SYSTEM; FUNCTIONAL GENOMICS; MUTAGENESIS; SEQUENCE; PLANTS; COLLECTION; MECHANISMS; MICRORNAS; REPAIR AB Tandemly arrayed genes (TAGs) or gene clusters are prevalent in higher eukaryotic genomes. For example, approximately 17% of genes are organized in tandem in the model plant Arabidopsis thaliana. The genetic redundancy created by TAGs presents a challenge for reverse genetics. As molecular scissors, engineered zinc finger nucleases (ZFNs) make DNA double-strand breaks in a sequence-specific manner. ZFNs thus provide a means to delete TAGs by creating two double-strand breaks in the gene cluster. Using engineered ZFNs, we successfully targeted seven genes from three TAGs on two Arabidopsis chromosomes, including the well-known RPP4 gene cluster, which contains eight resistance (R) genes. The resulting gene cluster deletions ranged from a few kb to 55 kb with frequencies approximating 1% in somatic cells. We also obtained large chromosomal deletions of similar to 9 Mb at approximately one tenth the frequency, and gene cluster inversions and duplications also were achieved. This study demonstrates the ability to use sequence-specific nucleases in plants to make targeted chromosome rearrangements and create novel chimeric genes for reverse genetics and biotechnology. C1 [Qi, Yiping; Li, Xiaohong; Zhang, Yong; Starker, Colby G.; Baltes, Nicholas J.; Zhang, Feng; Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Qi, Yiping; Li, Xiaohong; Zhang, Yong; Starker, Colby G.; Baltes, Nicholas J.; Zhang, Feng; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Zhang, Yong] Univ Elect Sci & Technol China, Sch Life Sci & Technol, Dept Biotechnol, Chengdu 610054, Peoples R China. [Sander, Jeffry D.; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Reyon, Deepak; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Reyon, Deepak] Iowa State Univ, Dept Genet Dev & Cell Biol, Interdept Grad Program Bioinformat & Computat Bio, Ames, IA 50011 USA. RP Voytas, DF (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. EM Voytas@umn.edu FU National Science Foundation [MCB 0209818, DBI 0923827]; National Institutes of Health (NIH); Chief Science Officer of Cellectis Plant Sciences; [DP1 GM105378]; [R01 GM088040] FX We thank all members of the Voytas lab for helpful discussions and suggestions. This work is supported by grants from the National Science Foundation (MCB 0209818 and DBI 0923827) to D.F.V. and a National Institutes of Health (NIH) Director's Pioneer Award DP1 GM105378 (J.K.J.) and NIH R01 GM088040 to J.K.J.D.F.V. has a financial interest in and serves as Chief Science Officer of Cellectis Plant Sciences. These interests have been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies. J.K.J. has a financial interest in Transposagen Biopharmaceuticals. J.K.J.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. NR 48 TC 26 Z9 29 U1 2 U2 30 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD OCT 1 PY 2013 VL 3 IS 10 BP 1707 EP 1715 DI 10.1534/g3.113.006270 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 232IJ UT WOS:000325486500009 PM 23979943 ER PT J AU Knights, D Lassen, KG Xavier, RJ AF Knights, Dan Lassen, Kara G. Xavier, Ramnik J. TI Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome SO GUT LA English DT Article DE INFLAMMATORY BOWEL DISEASE; GENETICS; INTESTINAL BACTERIA; CROHN'S DISEASE; ULCERATIVE COLITIS ID CHRONIC INTESTINAL INFLAMMATION; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; CLOSTRIDIUM-DIFFICILE; HUMAN FECES; SP NOV.; SUSCEPTIBILITY; CELLS; NOD2; VARIANTS AB Studies of the genetics underlying inflammatory bowel diseases have increased our understanding of the pathways involved in both ulcerative colitis and Crohn's disease and focused attention on the role of the microbiome in these diseases. Full understanding of pathogenesis will require a comprehensive grasp of the delicate homeostasis between gut bacteria and the human host. In this review, we present current evidence of microbiome-gene interactions in the context of other known risk factors and mechanisms, and describe the next steps necessary to pair genetic variant and microbiome sequencing data from patient cohorts. We discuss the concept of dysbiosis, proposing that the functional composition of the gut microbiome may provide a more consistent definition of dysbiosis and may more readily provide evidence of genome-microbiome interactions in future exploratory studies. C1 [Knights, Dan; Lassen, Kara G.; Xavier, Ramnik J.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Knights, Dan; Lassen, Kara G.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Knights, Dan] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St,Simches 7222, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu FU Crohn's and Colitis Foundation of America Genetics Initiative; NIH [DK097485, DK062432] FX This work was supported by funding from the Crohn's and Colitis Foundation of America Genetics Initiative as well as NIH grants DK097485 and DK062432 to RJX. NR 52 TC 111 Z9 114 U1 9 U2 60 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD OCT PY 2013 VL 62 IS 10 BP 1505 EP 1510 DI 10.1136/gutjnl-2012-303954 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218HC UT WOS:000324422400021 PM 24037875 ER PT J AU Brown, KK Viana, LM Helwig, CC Artunduaga, MA Quintanilla-Dieck, L Jarrin, P Osorno, G McDonough, B DePalma, SR Eavey, RD Seidman, JG Seidman, CE AF Brown, Kerry K. Viana, Lucas M. Helwig, Cecilia C. Artunduaga, Maria A. Quintanilla-Dieck, Lourdes Jarrin, Patricia Osorno, Gabriel McDonough, Barbara DePalma, Steven R. Eavey, Roland D. Seidman, Jonathan G. Seidman, Christine E. TI HOXA2 Haploinsufficiency in Dominant Bilateral Microtia and Hearing Loss SO HUMAN MUTATION LA English DT Article DE microtia; hearing loss; exome sequencing; HOXA2 ID HOMEOTIC TRANSFORMATION; GENE; MUTATION; FAMILY AB Microtia is a rare, congenital malformation of the external ear that in some cases has a genetic etiology. We ascertained a three-generation family with bilateral microtia and hearing loss segregating as an autosomal dominant trait. Exome sequencing of affected family members detected only seven shared, rare, heterozygous, nonsynonymous variants, including one protein truncating variant, a HOXA2 nonsense change (c.703C>T, p.Q235*). The HOXA2 variant was segregated with microtia and hearing loss in the family and was not seen in 6,500 individuals sequenced by the NHLBI Exome Sequencing Project or in 218 control individuals sequenced in this study. HOXA2 has been shown to be critical for outer and middle ear development through mouse models and has previously been associated with autosomal recessive bilateral microtia. Our data extend these conclusions and define HOXA2 haploinsufficiency as the first genetic cause for autosomal-dominant nonsyndromic microtia. (C) 2013 Wiley Periodicals, Inc. C1 [Brown, Kerry K.; Viana, Lucas M.; McDonough, Barbara; DePalma, Steven R.; Seidman, Jonathan G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Brown, Kerry K.; McDonough, Barbara; Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Viana, Lucas M.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Viana, Lucas M.] Univ Brasilia, Fac Hlth Sci, Brasilia, DF, Brazil. [Helwig, Cecilia C.] Geisinger Med Ctr, Dept Pediat Otolaryngol, Danville, PA 17822 USA. [Artunduaga, Maria A.] Univ Chicago, Med Ctr, Dept Surg, Sect Plast & Reconstruct Surg, Chicago, IL 60637 USA. [Quintanilla-Dieck, Lourdes] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Jarrin, Patricia] Hosp Un Canto Vida, Fdn Tierra Nueva, Quito, Ecuador. [Osorno, Gabriel] Univ Nacl Colombia, Fac Med, Unidad Cirugia Plast, Bogota, Colombia. [DePalma, Steven R.; Seidman, Christine E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Eavey, Roland D.] Vanderbilt Univ, Med Ctr, Dept Otolaryngol, Vanderbilt Bill Wilkerson Ctr, Nashville, TN 37232 USA. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, 77 Ave Louis Pasteur,NRB 256, Boston, MA 02115 USA. EM cseidman@genetics.med.harvard.edu FU Howard Hughes Medical Institute; NHLBI FX Grant sponsors: Howard Hughes Medical Institute; NHLBI. NR 18 TC 4 Z9 5 U1 0 U2 5 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 OCT PY 2013 VL 34 IS 10 BP 1347 EP 1351 DI 10.1002/humu.22367 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 222SW UT WOS:000324752700005 PM 23775976 ER PT J AU Machtinger, R Combelles, CMH Missmer, SA Correia, KF Williams, P Hauser, R Racowsky, C AF Machtinger, Ronit Combelles, Catherine M. H. Missmer, Stacey A. Correia, Katharine F. Williams, Paige Hauser, Russ Racowsky, Catherine TI Bisphenol-A and human oocyte maturation in vitro SO HUMAN REPRODUCTION LA English DT Article DE bisphenol-A; human oocyte; meiosis; meiotic maturation; in vitro ID ENDOCRINE-DISRUPTING CHEMICALS; CYTOPLASMIC MATURATION; EMBRYO QUALITY; HUMAN EXPOSURE; HUMAN HEALTH; FERTILIZATION; MOUSE; WOMEN; POPULATION; MECHANISMS AB Does exposure to bisphenol-A (BPA) affect the maturation of human oocytes in vitro? There was a doseresponse association of BPA exposure with altered human oocyte maturation in vitro. There is widespread exposure of the general population to BPA. BPA has been detected in the human follicular fluid. Animal studies have shown that BPA exposure is associated with maturation arrest and spindle abnormalities in maturing oocytes. A randomized trial, using 352 clinically discarded oocytes from 121 patients. The study population was drawn from patients undergoing IVF/ICSI cycles in our program at Brigham and Womens Hospital from March 2011 to April 2012. Oocytes from only one cycle for each patient were included in the study. Cycles with at least two germinal vesicle stage oocytes were included with random allocation of one oocyte to culture for 30 h without BPA and remaining sibling oocytes to medium-containing BPA (20, 200 ng/ml or 20 g/ml). Oocytes were fixed and labeled for tubulin, actin and chromatin and examined with immunofluorescence and confocal microscopy. Oocytes were assessed for meiotic stage (n 292), and those at metaphase II (MII, n 175) were further classified according to their spindle configurations and patterns of chromosome alignment. McNemars test was used to compare dichotomized maturation status. Generalized estimating equations were used to account for the correlation between oocytes from the same woman and for the spindle analysis. As the BPA dose increased, there was a decrease in the percentage of oocytes that progressed to MII (P 0.002) and increases in the percentage of oocytes that were degenerated (P 0.01) or that had undergone spontaneous activation (P 0.007). Among MII oocytes, as the BPA dose increased, there was a significant trend (by test for trend) for a decreased incidence of bipolar spindles (P 0.0001) and aligned chromosomes (P 0.02). Although we used sibling oocytes to overcome potential confounders, such as infertility diagnosis and maternal age, additional studies with a larger number of oocytes are required to confirm the present results. Having access only to clinically discarded oocytes, we were limited to evaluating only those oocytes that failed to mature in vivo despite having been exposed to gonadotrophin stimulation and the ovulatory trigger of HCG. To our knowledge, this is the first study investigating the effect of BPA on oocyte meiotic maturation, spindle morphology and chromosome alignment in human oocytes. Together with prior animal studies, the data support the negative influences of BPA on cell cycle progression, spindle architecture and chromosome organization during oocyte maturation. Furthermore, the increased rates of abnormal maturation in oocytes exposed to BPA may be relevant to our understanding of the decrease in fertility reported in the last decades. This study was funded by the NIEHS Center Grant Pilot Project (P30-ES000002). R.M. was sponsored by a fellowship from the Environmental Health Fund, Israel and by the Frederick L. Hisaw Endowment, Harvard School of Public Health. There are no conflicts of interest. n/a. C1 [Machtinger, Ronit; Missmer, Stacey A.; Correia, Katharine F.; Racowsky, Catherine] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Machtinger, Ronit; Missmer, Stacey A.; Correia, Katharine F.; Hauser, Russ; Racowsky, Catherine] Harvard Univ, Sch Med, Boston, MA USA. [Combelles, Catherine M. H.] Middlebury Coll, Dept Biol, Middlebury, VT USA. [Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Williams, Paige] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Fertil Ctr, Boston, MA USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Racowsky, C (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St,ASB 1 3,Rm 082, Boston, MA 02115 USA. EM cracowsky@partners.org FU NIEHS Center Grant Pilot Project [P30-ES000002]; Environmental and Health Foundation, Israel; Frederick L. Hisaw Endowment, Harvard School of Public Health FX This study was funded by the NIEHS Center Grant Pilot Project (P30-ES000002). R.M. was partially funded by the Environmental and Health Foundation, Israel and by the Frederick L. Hisaw Endowment, Harvard School of Public Health. NR 38 TC 34 Z9 35 U1 4 U2 32 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD OCT PY 2013 VL 28 IS 10 BP 2735 EP 2745 DI 10.1093/humrep/det312 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 223UI UT WOS:000324836300016 PM 23904465 ER PT J AU Grogg, K Zhu, XP Min, CH Winey, B Bortfeld, T Paganetti, H Shih, HA El Fakhri, G AF Grogg, Kira Zhu, Xuping Min, Chul Hee Winey, Brian Bortfeld, Thomas Paganetti, Harald Shih, Helen A. El Fakhri, Georges TI Feasibility of Using Distal Endpoints for In-Room PET Range Verification of Proton Therapy SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Hadron therapy; positron emission tomography (PET); proton beams ID POSITRON-EMISSION-TOMOGRAPHY; MONTE-CARLO SIMULATIONS; DOSE RECONSTRUCTION; RADIATION-THERAPY; VIVO VERIFICATION; BEAM; RADIOTHERAPY; HETEROGENEITIES; IMPLEMENTATION; IRRADIATION AB In an effort to verify the dose delivery in proton therapy, positron emission tomography (PET) scans have been employed to measure the distribution of beta+ radioactivity produced from nuclear reactions of the protons with native nuclei. Since the dose and PET distributions are difficult to compare directly, the range verification is currently carried out by comparing measured and Monte Carlo (MC) simulation predicted PET distributions. In order to reduce the reliance on MC, simulated PET (simPET) and dose distal endpoints were compared to explore the feasibility of using distal endpoints for in-room PET range verification. MC simulations were generated for six head and neck patients with corrections for radiological decay, biological washout, and PET resolution. One-dimensional profiles of the dose and simPET were examined along the direction of the beam and covering the cross section of the beam. The chosen endpoints of the simPET (x-intercept of the linear fit to the distal falloff) and planned dose (20%-50% of maximum dose) correspond to where most of the protons are below the threshold energy for the nuclear reactions. The difference in endpoint range between the distal surfaces of the dose and MC-PET were compared and the spread of range differences was assessed. Among the six patients, the mean difference between MC-PET and dose depth was found to be -1.6 mm to +0.5 mm between patients, with a standard deviation of 1.1 to 4.0 mm across the individual beams. In clinical practice, regions with deviations beyond the safety margin need to be examined more closely and can potentially lead to adjustments to the treatment plan. C1 [Grogg, Kira; Zhu, Xuping; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Min, Chul Hee] Yonsei Univ, Coll Hlth Sci, Dept Radiol Sci, Wonju 220710, Gangwon Do, South Korea. [Winey, Brian; Bortfeld, Thomas; Paganetti, Harald; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Grogg, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. FU National Institutes of Health [R21CA153455, R21EB12823, T32RB013180] FX Manuscript received December 04, 2012; revised May 21, 2013 and August 05, 2013; accepted August 08, 2013. Date of publication September 12, 2013; date of current version October 09, 2013. This work was supported in part by the National Institutes of Health under Grant Nos. R21CA153455, R21EB12823, and T32RB013180. Some of this work was previously reported in the IEEE Nuclear Science Symposium Conference Record (NSS/MIC), 2012. NR 35 TC 4 Z9 4 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 EI 1558-1578 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 2013 VL 60 IS 5 BP 3290 EP 3297 DI 10.1109/TNS.2013.2278140 PN 1 PG 8 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 236VJ UT WOS:000325827200016 PM 24464031 ER PT J AU Ouyang, JS Chun, SY Petibon, Y Bonab, AA Alpert, N El Fakhri, G AF Ouyang, Jinsong Chun, Se Young Petibon, Yoann Bonab, Ali A. Alpert, Nathaniel El Fakhri, Georges TI Bias Atlases for Segmentation-Based PET Attenuation Correction Using PET-CT and MR SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Attenuation correction; PET-MR ID WHOLE-BODY PET/MRI; IMAGE REGISTRATION; DISEASE AB This study was to obtain voxel-wise PET accuracy and precision using tissue-segmentation for attenuation correction. We applied multiple thresholds to the CTs of 23 patients to classify tissues. For six of the 23 patients, MR images were also acquired. The MR fat/in-phase ratio images were used for fat segmentation. Segmented tissue classes were used to create attenuation maps, which were used for attenuation correction in PET reconstruction. PET bias images were then computed using the PET reconstructed with the original CT as the reference. We registered the CTs for all the patients and transformed the corresponding bias images accordingly. We then obtained the mean and standard deviation bias atlas using all the registered bias images. Our CT-based study shows that four-class segmentation (air, lungs, fat, other tissues), which is available on most PET-MR scanners, yields 15.1%, 4.1%, 6.6%, and 12.9% RMSE bias in lungs, fat, non-fat soft-tissues, and bones, respectively. An accurate fat identification is achievable using fat/in-phase MR images. Furthermore, we have found that three-class segmentation (air, lungs, other tissues) yields less than 5% standard deviation of bias within the heart, liver, and kidneys. This implies that three-class segmentation can be sufficient to achieve small variation of bias for imaging these three organs. Finally, we have found that inter- and intra-patient lung density variations contribute almost equally to the overall standard deviation of bias within the lungs. C1 [Ouyang, Jinsong; Petibon, Yoann; Bonab, Ali A.; Alpert, Nathaniel; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Radiol Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Ouyang, Jinsong; Chun, Se Young; Bonab, Ali A.; Alpert, Nathaniel; El Fakhri, Georges] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chun, Se Young] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Petibon, Yoann] Univ Paris 06, INSERM, UMR S 678, Lab Imagerie Fonct, F-75634 Paris, France. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Ctr Adv Radiol Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM ouyang.jinsong@mgh.harvard.edu OI Chun, Se Young/0000-0001-8739-8960 FU National Institutes of Health (NIH) [R21EB12326, R01HL110241] FX Manuscript received October 23, 2012; revised December 31, 2012, March 20, 2013, and May 23, 2013; accepted August 08, 2013. Date of publication September 16, 2013; date of current version October 09, 2013. This work was supported in part by research grants from the National Institutes of Health (NIH) under grants R21EB12326 and R01HL110241. (Corresponding author: J. Ouyang.) NR 33 TC 17 Z9 17 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 EI 1558-1578 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 2013 VL 60 IS 5 BP 3373 EP 3382 DI 10.1109/TNS.2013.2278624 PN 1 PG 10 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 236VJ UT WOS:000325827200024 PM 24966415 ER PT J AU Infusino, SA Ojha, S Maurer, R Sadow, PM Faquin, WC Hartnick, CJ AF Infusino, Scott A. Ojha, Shilpa Maurer, Rie Sadow, Peter M. Faquin, William C. Hartnick, Christopher J. TI The utility of histopathology in identifying structural differences among layers of the lamina propria SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Lamina propria; Histopathology; Vocal fold; Development; Optical coherence tomography ID HUMAN VOCAL FOLD AB Objective: The purpose of this study is to assess the modality of laryngeal histopathology in identifying 1, 2, or 3 layers in the lamina propria. Methods: Blinded analysis was performed, with a set of histophathologic slides where the magnification and localized regions shown were all standardized. Two senior pathologists with experience reviewing laryngologic histophathology were asked to assess whether the vocal fold lamina propria they evaluated contained 1, 2, or 3 layers. Their ability to accurately assess this was calculated. Results: The first pathologist correctly identified 13 of 25 (52%) specimens. The second identified 19 of 25 (76%) specimens after receiving gold referents before the test. No significant difference was seen between the pathologists' interpretations (McNemar test; p = 0.0833). Conclusion: Our results show the difficulty of using histopathology to distinguish layers in the lamina propria even when the reviewers are senior pathologists. These findings imply that more objective modalities for such analyses may be beneficial. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Infusino, Scott A.; Ojha, Shilpa; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Div Pediat Otolaryngol, Boston, MA 02114 USA. [Maurer, Rie] Brigham & Womens Hosp, Ctr Clin Invest, Boston, MA 02115 USA. [Sadow, Peter M.; Faquin, William C.] Massachusetts Eye & Ear Infirm, Dept Pathol, Boston, MA 02114 USA. RP Infusino, SA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Scott_Infusino@MEEI.Harvard.edu NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD OCT PY 2013 VL 77 IS 10 BP 1651 EP 1654 DI 10.1016/j.ijporl.2013.07.018 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 231WI UT WOS:000325448700006 PM 24001615 ER PT J AU Wiggs, JL Pierce, EA AF Wiggs, Janey L. Pierce, Eric A. TI Genetic Testing for Inherited Eye Disease Who Benefits? SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID THERAPY; GLAUCOMA C1 [Wiggs, Janey L.; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 NR 7 TC 11 Z9 11 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2013 VL 131 IS 10 BP 1265 EP 1266 DI 10.1001/jamaophthalmol.2013.4509 PG 2 WC Ophthalmology SC Ophthalmology GA 232HK UT WOS:000325483400004 PM 23949187 ER PT J AU Faez, S Loewenstein, JI Sobrin, L AF Faez, Sepideh Loewenstein, John I. Sobrin, Lucia TI Detection of Antiretinal Autoantibodies in Serum by Western Blotting Reply SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Faez, Sepideh; Loewenstein, John I.; Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sobrin, L (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD OCT PY 2013 VL 131 IS 10 DI 10.1001/jamaophthalmol.2013.4588 PG 1 WC Ophthalmology SC Ophthalmology GA 232HK UT WOS:000325483400033 ER PT J AU Winston, FK McDonald, CC McGehee, DV AF Winston, Flaura K. McDonald, Catherine C. McGehee, Daniel V. TI Are We Doing Enough to Prevent the Perfect Storm? Novice Drivers, ADHD, and Distracted Driving SO JAMA PEDIATRICS LA English DT Editorial Material ID PROGRAM; TEENS C1 [Winston, Flaura K.; McDonald, Catherine C.] Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, Philadelphia, PA 19104 USA. [Winston, Flaura K.] Univ Penn, Sch Med, Perelman Sch Med, Div Gen Pediat, Philadelphia, PA 19104 USA. [Winston, Flaura K.] Univ Penn, Sch Med, Perelman Sch Med, Leonard David Inst Hlth Econ, Philadelphia, PA 19104 USA. [McDonald, Catherine C.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [McGehee, Daniel V.] Univ Iowa, Human Factors & Vehicle Safety Res Div, Publ Policy Ctr, Injury Prevent Res Ctr, Iowa City, IA USA. RP Winston, FK (reprint author), Childrens Hosp Philadelphia, Ctr Injury Res & Prevent, 3535 Market St,11th Fl, Philadelphia, PA 19104 USA. EM flaura@mail.med.upenn.edu FU NINR NIH HHS [K99 NR013548] NR 15 TC 2 Z9 2 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2013 VL 167 IS 10 BP 892 EP 894 DI 10.1001/jamapediatrics.2013.2315 PG 3 WC Pediatrics SC Pediatrics GA 232GQ UT WOS:000325480900005 PM 23939682 ER PT J AU Sanderson, A Zurakowski, D Wolfe, J AF Sanderson, Amy Zurakowski, David Wolfe, Joanne TI Clinician Perspectives Regarding the Do-Not-Resuscitate Order SO JAMA PEDIATRICS LA English DT Article ID OF-LIFE CARE; DECISION-MAKING; PALLIATIVE CARE; HEALTH-CARE; END; DISCUSSIONS; PERCEPTIONS; CHILDREN AB IMPORTANCE While data exist regarding the frequency and timing of the do-not-resuscitate (DNR) order in children, little is known about clinician attitudes and behaviors regarding this order. OBJECTIVE To identify clinician attitudes regarding the meaning, implication, and timing of the DNR order for pediatric patients. DESIGN Physicians and nurses from practice settings where advance care planning typically takes place were surveyed regarding their attitudes and behaviors about DNR orders. RESULTS In total, 107 physicians and 159 nurses responded to the survey (N = 266). There was substantial variability in the interpretation of the DNR order. Most clinicians (66.9%) believe that a DNR order indicates limitation of resuscitative measures only on cardiopulmonary arrest. In reality, however, more than 85% believe that care changes beyond response to cardiopulmonary arrest, varying from increased attention to comfort to less clinician attentiveness. In addition, most clinicians reported that resuscitation status discussions take place later in the illness course than is ideal. CONCLUSIONS AND RELEVANCE Clinicians use the DNR order not only as a guide for therapeutic decisions during a cardiopulmonary arrest but also as a surrogate for broader treatment directives. Most clinicians believe that DNR discussions should take place earlier than they actually do. Interventions aimed at improving clinician knowledge and skills in advance care discussions as well as the development of orders that address overall goals of care may improve care for children with serious illness. C1 [Sanderson, Amy; Zurakowski, David] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, Boston, MA 02115 USA. RP Sanderson, A (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Bader 634, Boston, MA 02115 USA. EM amy.sanderson@childrens.harvard.edu NR 18 TC 6 Z9 6 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2013 VL 167 IS 10 BP 954 EP 958 DI 10.1001/jamapediatrics.2013.2204 PG 5 WC Pediatrics SC Pediatrics GA 232GQ UT WOS:000325480900018 PM 23979224 ER PT J AU Adams, MC Fifer, MA Jiang, YD AF Adams, M. Christopher Fifer, Michael A. Jiang, Yandong TI New-onset left bundle branch block immediately following noncardiac surgery under combined general and epidural anesthesia SO JOURNAL OF ANESTHESIA LA English DT Letter DE Left bundle branch block; Myocardium infarction; Epidural and general anesthesia C1 [Adams, M. Christopher; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Fifer, Michael A.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM yjiang@partners.org NR 2 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0913-8668 EI 1438-8359 J9 J ANESTH JI J. Anesth. PD OCT PY 2013 VL 27 IS 5 BP 795 EP 796 DI 10.1007/s00540-013-1605-9 PG 2 WC Anesthesiology SC Anesthesiology GA 234DI UT WOS:000325620400030 PM 23564335 ER PT J AU Chase, MH AF Chase, Michael H. TI A unified survival theory of the functioning of the hypocretinergic system SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE hypocretin; orexin; behaviors; survival ID CORTICOTROPIN-RELEASING-FACTOR; COERULEUS-NORADRENERGIC SYSTEM; HYPOTHALAMIC DEFENSIVE SYSTEM; SLEEP BEHAVIOR DISORDER; VENTRAL TEGMENTAL AREA; OREXIN KNOCKOUT MICE; BROWN ADIPOSE-TISSUE; HYPOCRETIN/OREXIN NEURONS; ENERGY HOMEOSTASIS; SPINAL-CORD AB This article advances the theory that the hypocretinergic (orexinergic) system initiates, coordinates, and maintains survival behaviors and survival-related processes (i.e., the Unified Survival Theory of the Functioning of the Hypocretinergic System or "Unified Hypocretinergic Survival Theory"). A priori presumptive support for the Unified Hypocretinergic Survival Theory emanates from the fact that neurons that contain hypocretin are located in the key executive central nervous system (CNS) site, the lateral hypothalamus, that for decades has been well-documented to govern core survival behaviors such as fight, flight, and food consumption. In addition, the hypocretinergic system exhibits the requisite morphological and electrophysiological capabilities to control survival behaviors and related processes. Complementary behavioral data demonstrate that all facets of "survival" are coordinated by the hypocretinergic system and that hypocretinergic directives are not promulgated except during survival behaviors. Importantly, it has been shown that survival behaviors are selectively impacted when the hypocretinergic system is impaired or rendered nonfunctional, whereas other behaviors are relatively unaffected. The Unified Hypocretinergic Survival Theory resolves the disparate, perplexing, and often paradoxical-appearing results of previous studies; it also provides a foundation for future hypothesis-driven basic science and clinical explorations of the hypocretinergic system. C1 [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, WebSci Int, Los Angeles, CA 90024 USA. RP Chase, MH (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM mchase@websciences.org NR 197 TC 9 Z9 9 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2013 VL 115 IS 7 BP 954 EP 971 DI 10.1152/japplphysiol.00700.2012 PG 18 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 231YX UT WOS:000325455400002 PM 23640599 ER PT J AU Neviani, P Harb, JG Oaks, JJ Santhanam, R Walker, CJ Ellis, JJ Ferenchak, G Dorrance, AM Paisie, CA Eiring, AM Ma, YH Mao, HC Zhang, B Wunderlich, M May, PC Sun, CD Saddoughi, SA Bielawski, J Blum, W Klisovic, RB Solt, JA Byrd, JC Volinia, S Cortes, J Huettner, CS Koschmieder, S Holyoake, TL Devine, S Caligiuri, MA Croce, CM Garzon, R Ogretmen, B Arlinghaus, RB Chen, CS Bittman, R Hokland, P Roy, DC Milojkovic, D Apperley, J Goldman, JM Reid, A Mulloy, JC Bhatia, R Marcucci, G Perrotti, D AF Neviani, Paolo Harb, Jason G. Oaks, Joshua J. Santhanam, Ramasamy Walker, Christopher J. Ellis, Justin J. Ferenchak, Gregory Dorrance, Adrienne M. Paisie, Carolyn A. Eiring, Anna M. Ma, Yihui Mao, Hsiaoyin C. Zhang, Bin Wunderlich, Mark May, Philippa C. Sun, Chaode Saddoughi, Sahar A. Bielawski, Jacek Blum, William Klisovic, Rebecca B. Solt, Janelle A. Byrd, John C. Volinia, Stefano Cortes, Jorge Huettner, Claudia S. Koschmieder, Steffen Holyoake, Tessa L. Devine, Steven Caligiuri, Michael A. Croce, Carlo M. Garzon, Ramiro Ogretmen, Besim Arlinghaus, Ralph B. Chen, Ching-Shih Bittman, Robert Hokland, Peter Roy, Denis-Claude Milojkovic, Dragana Apperley, Jane Goldman, John M. Reid, Alistair Mulloy, James C. Bhatia, Ravi Marcucci, Guido Perrotti, Danilo TI PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; PROTEIN PHOSPHATASE 2A; COMPLETE MOLECULAR REMISSION; BLAST-CRISIS CML; BCR-ABL; BETA-CATENIN; HEMATOPOIETIC-CELLS; IMATINIB MESYLATE; IN-VIVO; MULTIPLE-SCLEROSIS AB The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 kinase activity in CML progenitors. However, CML quiescent HSCs are TKI resistant and represent a BCR-ABL1 kinase-independent disease reservoir. Here we have shown that persistence of leukemic HSCs in BM requires inhibition of the tumor suppressor protein phosphatase 2A (PP2A) and expression - but not activity - of the BCR-ABL1 oncogene. Examination of HSCs from CML patients and healthy individuals revealed that PP2A activity was suppressed in CML compared with normal HSCs. TKI-resistant CML quiescent HSCs showed increased levels of BCR-ABL1, but very low kinase activity. BCR-ABL1 expression, but not kinase function, was required for recruitment of JAK2, activation of a JAK2/beta-catenin survival/self-renewal pathway, and inhibition of PP2A. PP2A-activating drugs (PADs) markedly reduced survival and self-renewal of CML quiescent HSCs, but not normal quiescent HSCs, through BCR-ABL1 kinase-independent and PP2A-mediated inhibition of JAK2 and beta-catenin. This led to suppression of human leukemic, but not normal, HSC/progenitor survival in BM xenografts and interference with long-term maintenance of BCR-ABL1-positive HSCs in serial transplantation assays. Targeting the JAK2/PP2A/beta-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and. relieve lifelong patient dependence on TKIs. C1 [Neviani, Paolo; Harb, Jason G.; Oaks, Joshua J.; Santhanam, Ramasamy; Walker, Christopher J.; Ellis, Justin J.; Ferenchak, Gregory; Paisie, Carolyn A.; Eiring, Anna M.; Volinia, Stefano; Croce, Carlo M.; Garzon, Ramiro; Perrotti, Danilo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA. [Dorrance, Adrienne M.; Ma, Yihui; Mao, Hsiaoyin C.; Klisovic, Rebecca B.; Solt, Janelle A.; Byrd, John C.; Devine, Steven; Caligiuri, Michael A.; Garzon, Ramiro; Chen, Ching-Shih; Marcucci, Guido] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Mao, Hsiaoyin C.; Blum, William; Klisovic, Rebecca B.; Solt, Janelle A.; Byrd, John C.; Devine, Steven; Caligiuri, Michael A.; Croce, Carlo M.; Garzon, Ramiro; Chen, Ching-Shih; Marcucci, Guido; Perrotti, Danilo] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Zhang, Bin] City Hope Natl Med Ctr, Dept Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA. [Wunderlich, Mark; Mulloy, James C.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [May, Philippa C.; Milojkovic, Dragana; Apperley, Jane; Goldman, John M.; Perrotti, Danilo] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Haematol, London, England. [Sun, Chaode] CUNY Queens Coll, Dept Chem & Biochem, Flushing, NY 11367 USA. [Saddoughi, Sahar A.; Bielawski, Jacek; Ogretmen, Besim] Med Univ S Carolina, Dept Biochem & Mol Biol, Hollings Canc Ctr, Charleston, SC 29425 USA. [Volinia, Stefano] Univ Ferrara, Dept Morphol & Embryol, I-44100 Ferrara, Italy. [Cortes, Jorge] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Cortes, Jorge] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Koschmieder, Steffen] Univ Hosp Aachen, Dept Internal Med Hematol & Med Oncol, Aachen, Germany. [Holyoake, Tessa L.] Univ Glasgow, Paul Gorman Leukaemia Res Ctr, Inst Canc Sci, Glasgow, Lanark, Scotland. [Arlinghaus, Ralph B.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. [Hokland, Peter] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark. [Roy, Denis-Claude] Maisonneuve Rosemont Hosp, Dept Hematol Oncol, Montreal, PQ, Canada. [Roy, Denis-Claude] Univ Montreal, Montreal, PQ, Canada. RP Perrotti, D (reprint author), Ohio State Univ, Ctr Comprehens Canc, 892 Biomed Res Tower,460 West 12th Ave, Columbus, OH 43210 USA. EM danilo.perrotti@osumc.edu RI Blum, William/E-2769-2011; Klisovic, Rebecca/E-3401-2011; Garzon, Ramiro/E-3104-2011; Holyoake, Tessa/M-3668-2015; OI Holyoake, Tessa/0000-0002-0608-6066; Hokland, Peter/0000-0002-1177-9756; Volinia, Stefano/0000-0003-0910-3893 FU NIH [CA095512, CA16058, CA140158, CA88932, CA95684, CA49639, HL-083187, USPHS MO1 RR08084]; US Army CML Research Program [W81XWH-07-1-0270]; Leukemia and Lymphoma Society Scholarship; American-Italian Cancer Foundation; Fonds de la Recherche en Sante du Quebec; Danish Medical Research Council; Danish Cancer Society; Karen Elise Jensen Foundation; Alex's Lemonade Stand; Cancer Research UK [C11074/A11008]; [SCOR 7004-11] FX We thank B. Perazzona, R. Van Etten, X. Jiang, and J. Van Brocklyn for providing reagents; C.J. Eaves, J. Cancelas, and T.S. Ong for scientific discussion; J. Perrin for helping procure CML specimens; and S. Lee for editorial assistance. This work is dedicated to Carolyn Kraemer and her family, Bob Mills, and Tom Archdeacon for supporting this work through the Leukemia and Lymphoma Society. This work was supported by NIH grants CA095512 (to D. Perrotti), CA16058 (to The Ohio State University Comprehensive Cancer Center), CA140158 (to J.C. Byrd), CA88932 (to B. Ogretmen), CA95684 (to R. Bhatia), CA49639 (to R.B. Arlinghaus), HL-083187 (to R. Bittman), and USPHS MO1 RR08084 (to Cincinnati Children's Hospital); by US Army CML Research Program grant W81XWH-07-1-0270 (to D. Perrotti); by the Leukemia and Lymphoma Society Scholarship (to D. Perrotti and J.C. Mulloy) and grant SCOR 7004-11 (to J.C. Byrd); by the American-Italian Cancer Foundation (to P. Neviani); by Fonds de la Recherche en Sante du Quebec (to D.-C. Roy); by the Danish Medical Research Council and the Danish Cancer Society and the Karen Elise Jensen Foundation (to P. Hokland); by Alex's Lemonade Stand (to J.C. Mulloy); and by Cancer Research UK grant C11074/A11008 (to T.L. Holyoake). NR 60 TC 72 Z9 73 U1 0 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2013 VL 123 IS 10 BP 4144 EP 4157 DI 10.1172/JCI68951 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 231UE UT WOS:000325443100012 PM 23999433 ER PT J AU Li, AL Yang, YY Gao, C Lu, JY Jeong, HW Liu, BH Tang, P Yao, XP Neuberg, D Huang, G Tenen, DG Chai, L AF Li, Ailing Yang, Youyang Gao, Chong Lu, Jiayun Jeong, Ha-Won Liu, Bee H. Tang, Ping Yao, Xiaopan Neuberg, Donna Huang, Gang Tenen, Daniel G. Chai, Li TI A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MIXED-LINEAGE LEUKEMIA; OKIHIRO-SYNDROME; TARGET GENES; SALL4; MLL; EXPRESSION; MUTATIONS; REGULATOR; PLURIPOTENCY AB The embryonic self-renewal factor SALL4 has been implicated in the development of human acute myeloid leukemia (AML). Transgenic mice expressing the human SALL4B allele develop AML, which indicates that this molecule contributes to leukemia development and maintenance. However, the underlying mechanism of SALL4-dependent ANIL progression is unknown. Using SALL4B transgenic mice, we observed that HoxA9 was significantly upregulated in SALL4B leukemic cells compared with wild-type controls. Downregulation of HoxA9 in SALL4B leukemic cells led to decreased replating capacity in vitro and delayed AML development in recipient mice. In primary human AML cells, downregulation. of SALL4 led to decreased HOXA9 expression and enhanced apoptosis. We found that SALL4 bound a specific region of the HOXA9 promoter in leukemic cells. SALL4 overexpression led to enhanced binding of histone activation markers at the HOXA9 promoter region, as well as increased HOXA9 expression in these cells. Furthermore, we observed that SALL4 interacted with mixed-lineage leukemia (MLL) and co-occupied the HOXA9 promoter region with MLL in AML leukemic cells, which suggests that a SALL4/MLL pathway may control HOXA9 expression. In summary, our findings revealed a molecular mechanism for SALL4 function in leukemogenesis and suggest that targeting of the SALL4/MLL/HOXA9 pathway would be an innovative approach in treating AML. C1 [Li, Ailing; Yang, Youyang; Gao, Chong; Lu, Jiayun; Jeong, Ha-Won; Tang, Ping; Chai, Li] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Joint Program Transfus Med, Boston, MA 02115 USA. [Liu, Bee H.; Tenen, Daniel G.] Natl Univ Singapore, Ctr Translat Med, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Yao, Xiaopan] Yale Univ, Sch Publ Hlth, Yale Ctr Analyt Sci, New Haven, CT USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Huang, Gang] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Program Canc Pathol, Cincinnati, OH 45229 USA. [Tenen, Daniel G.] Harvard Stem Cell Inst, Ctr Life Sci, Boston, MA USA. RP Chai, L (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Joint Program Transfus Med, 77 Ave Louis Pasteur,NRB652, Boston, MA 02115 USA. EM lchai@partners.org OI Tenen, Daniel/0000-0002-6423-3888 FU NIH [PO1 DK080665, CA66996, RO1 HL092437, PO1 HL095489]; Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award FX This work was supported in part by NIH grants PO1 DK080665 and CA66996 to D.G. Tenen and by NIH grants RO1 HL092437 and PO1 HL095489 to L. Chai. This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award (to D.G. Tenen). We thank Wee Joo Chng for assistance in obtaining AML samples and Nicole Tenen for assistance in preparation of the manuscript. NR 44 TC 11 Z9 12 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2013 VL 123 IS 10 BP 4195 EP 4207 DI 10.1172/JCI62891 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 231UE UT WOS:000325443100016 PM 24051379 ER PT J AU Ho, JE Chen, WY Chen, MH Larson, MG McCabe, EL Cheng, SS Ghorbani, A Coglianese, E Emilsson, V Johnson, AD Walter, S Franceschini, N O'Donnell, CJ Dehghan, A Lu, C Levy, D Newton-Cheh, C Lin, HH Felix, JF Schreiter, ER Vasan, RS Januzzi, JL Lee, RT Wang, TJ AF Ho, Jennifer E. Chen, Wei-Yu Chen, Ming-Huei Larson, Martin G. McCabe, Elizabeth L. Cheng, Susan Ghorbani, Anahita Coglianese, Erin Emilsson, Valur Johnson, Andrew D. Walter, Stefan Franceschini, Nora O'Donnell, Christopher J. Dehghan, Abbas Lu, Chen Levy, Daniel Newton-Cheh, Christopher Lin, Honghuang Felix, Janine F. Schreiter, Eric R. Vasan, Ramachandran S. Januzzi, James L. Lee, Richard T. Wang, Thomas J. CA CARDIoGRAM Consortium CHARGE Inflammation Working Grp CHARGE Heart Failure Working Grp TI Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RECEPTOR FAMILY-MEMBER; DECOMPENSATED HEART-FAILURE; SOLUBLE ST2; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; CELIAC-DISEASE; ACUTE DYSPNEA; SERUM-LEVELS; LARGE-SCALE; MAST-CELLS AB The suppression of turnorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response when bound to its ligand, IL-33. The other isoform is a soluble protein (sST2) that is thought to be a decoy receptor for IL-33 signaling. Elevated sST2 levels in serum are associated with an increased risk for cardiovascular disease. We investigated the determinants of sST2 plasma concentrations in 2,991 Framingham Offspring Cohort participants. While clinical and environmental factors explained some variation in sST2 levels, much of the variation in sST2 production was driven by genetic factors. In a genome-wide association study (GWAS), multiple SNPs within IL1RL1 (the gene encoding ST2) demonstrated associations with sST2 concentrations. Five missense variants of IL1RL1 correlated with higher sST2 levels in the GWAS and mapped to the intracellular domain of ST2, which is absent in sST2. In a cell culture model, IL1RL1 missense variants increased sST2 expression by inducing IL-33 expression and enhancing IL-33 responsiveness (via ST2L). Our data suggest that genetic variation in IL1RL1 can result in increased levels of sST2 and alter immune and inflammatory signaling through the ST2/IL-33 pathway. C1 [Ho, Jennifer E.; Chen, Ming-Huei; Larson, Martin G.; Cheng, Susan; Johnson, Andrew D.; O'Donnell, Christopher J.; Levy, Daniel; Newton-Cheh, Christopher; Lin, Honghuang; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Chen, Ming-Huei; Larson, Martin G.; Cheng, Susan; Johnson, Andrew D.; O'Donnell, Christopher J.; Levy, Daniel; Newton-Cheh, Christopher; Lin, Honghuang; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Ho, Jennifer E.] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Chen, Wei-Yu; Cheng, Susan; Lee, Richard T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol, Boston, MA USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Larson, Martin G.; Lu, Chen] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [McCabe, Elizabeth L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Ghorbani, Anahita; O'Donnell, Christopher J.; Newton-Cheh, Christopher; Januzzi, James L.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Coglianese, Erin] Loyola Univ Hlth Syst, Chicago, IL USA. [Emilsson, Valur] Iceland Heart Assoc, Kopavogur, Iceland. [Walter, Stefan] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Walter, Stefan] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Walter, Stefan; Dehghan, Abbas; Felix, Janine F.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Cambridge, MA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lin, Honghuang; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Schreiter, Eric R.] Univ Puerto Rico, Dept Chem, San Juan, PR 00936 USA. [Schreiter, Eric R.] Howard Hughes Med Inst, Ashburn, VA USA. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN 37232 USA. RP Wang, TJ (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2220 Pierce Ave,383 Preston Res Bldg, Nashville, TN 37232 USA. EM rlee@partners.org; thomas.j.wang@vanderbilt.edu RI Altshuler, David/A-4476-2009; Schreiber, Stefan/B-6748-2008; Willenborg, Christina/D-2668-2012; Lu, Chen/D-8514-2015; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; Johnson, Andrew/G-6520-2013; OI Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Lin, Honghuang/0000-0003-3043-3942; Ramachandran, Vasan/0000-0001-7357-5970; Altshuler, David/0000-0002-7250-4107; Schreiber, Stefan/0000-0003-2254-7771; Willenborg, Christina/0000-0001-5217-6882; Gudnason, Vilmundur/0000-0001-5696-0084; Felix, Janine/0000-0002-9801-5774 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix Inc. for genotyping services [N02-HL-6-4278]; NIH [R01-NS017950-28, R01-HL093328-01, R01 HL092930, R01-HL086875, 1K23-HL116780]; Boston University School of Medicine Department of Medicine Career Investment Award; Ellison Foundation; Taiwan National Science Council [101-2917-I-564-057]; AHA postdoctoral fellowship [13POST16940030]; NWO grant (veni) [916.12.154]; EUR fellowship; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center FX This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195), its contract with Affymetrix Inc. for genotyping services (N02-HL-6-4278), and NIH grants R01-NS017950-28 and R01-HL093328-01 (to R.S. Vasan), R01 HL092930 (to R.T. Lee), R01-HL086875 (to T.J. Wang), and 1K23-HL116780 (to J.E. Ho). J.E. Ho is supported by a Boston University School of Medicine Department of Medicine Career Investment Award. Measurement of sST2 was performed by Critical Diagnostics Inc. S. Cheng is supported by an award from the Ellison Foundation. W.-Y. Chen is supported by awards from the Taiwan National Science Council (101-2917-I-564-057) and an AHA postdoctoral fellowship (13POST16940030). A. Dehghan is supported by a NWO grant (veni, 916.12.154) and the EUR fellowship. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Please see Supplemental Acknowledgments for CHARGE and CARDIoGRAM consortium details. NR 50 TC 35 Z9 35 U1 1 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2013 VL 123 IS 10 BP 4208 EP 4218 DI 10.1172/JCI67119 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 231UE UT WOS:000325443100017 PM 23999434 ER PT J AU Wang, TJ Ngo, D Psychogios, N Dejam, A Larson, MG Vasan, RS Ghorbani, A O'Sullivan, J Cheng, S Rhee, EP Sinha, S McCabe, E Fox, CS O'Donnell, CJ Ho, JE Florez, JC Magnusson, M Pierce, KA Souza, AL Yu, Y Carter, C Light, PE Melander, O Clish, CB Gerszten, RE AF Wang, Thomas J. Ngo, Debby Psychogios, Nikolaos Dejam, Andre Larson, Martin G. Vasan, Ramachandran S. Ghorbani, Anahita O'Sullivan, John Cheng, Susan Rhee, Eugene P. Sinha, Sumita McCabe, Elizabeth Fox, Caroline S. O'Donnell, Christopher J. Ho, Jennifer E. Florez, Jose C. Magnusson, Martin Pierce, Kerry A. Souza, Amanda L. Yu, Yi Carter, Christian Light, Peter E. Melander, Olle Clish, Clary B. Gerszten, Robert E. TI 2-Aminoadipic acid is a biomarker for diabetes risk SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; LIFE-STYLE; MELLITUS; METABOLISM; SECRETION; FREQUENCY; OXIDATION; MARKER AB Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic beta cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans. C1 [Wang, Thomas J.; Ngo, Debby; Psychogios, Nikolaos; Dejam, Andre; O'Sullivan, John; Rhee, Eugene P.; Sinha, Sumita; Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Wang, Thomas J.; Ghorbani, Anahita; O'Donnell, Christopher J.; Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. [Wang, Thomas J.; Larson, Martin G.; Vasan, Ramachandran S.; Ghorbani, Anahita; Cheng, Susan; Fox, Caroline S.; O'Donnell, Christopher J.; Ho, Jennifer E.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wang, Thomas J.; Larson, Martin G.; Vasan, Ramachandran S.; Ghorbani, Anahita; Cheng, Susan; Fox, Caroline S.; O'Donnell, Christopher J.; Ho, Jennifer E.] Boston Univ, Sch Med, Framingham, MA USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. [Ngo, Debby] Harvard Univ, Sch Med, Div Pulm, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Ho, Jennifer E.] Boston Univ, Dept Med, Prevent Med Sect, Boston, MA 02215 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Rhee, Eugene P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Renal, Boston, MA USA. [Rhee, Eugene P.; Florez, Jose C.; Pierce, Kerry A.; Souza, Amanda L.; Clish, Clary B.; Gerszten, Robert E.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Rhee, Eugene P.; Florez, Jose C.; Pierce, Kerry A.; Souza, Amanda L.; Clish, Clary B.; Gerszten, Robert E.] Harvard, Cambridge, MA USA. [McCabe, Elizabeth] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Florez, Jose C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabets Unit, Boston, MA USA. [Florez, Jose C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Magnusson, Martin] Skane Univ Hosp, Dept Cardiol, Malmo, Sweden. [Magnusson, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Yu, Yi; Carter, Christian; Light, Peter E.] Univ Alberta, Dept Pharmacol, Alberta Diabet Inst, Edmonton, AB, Canada. [Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, Malmo, Sweden. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, 185 Cambridge St, Boston, MA 02114 USA. EM thomas.j.wang@vanderbilt.edu; rgerszten@partners.org OI Ho, Jennifer/0000-0002-7987-4768; Psychogios, Nikolaos/0000-0002-2747-6012; Magnusson, Martin/0000-0003-1710-5936; Ramachandran, Vasan/0000-0001-7357-5970 FU NIH [NO1-HC-25195, R01-DK-HL081572]; Leducq Foundation; Canadian Institutes of Health Research; American Heart Association FX This work was supported by NIH contract NO1-HC-25195, R01-DK-HL081572, the Leducq Foundation, the Canadian Institutes of Health Research, and the American Heart Association. NR 28 TC 77 Z9 77 U1 6 U2 36 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2013 VL 123 IS 10 BP 4309 EP 4317 DI 10.1172/JCI64801 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 231UE UT WOS:000325443100026 PM 24091325 ER PT J AU Wei, W Mok, SC Oliva, E Kim, SH Mohapatra, G Birrer, MJ AF Wei, Wei Mok, Samuel C. Oliva, Esther Kim, Sung-hoon Mohapatra, Gayatry Birrer, Michael J. TI FGF18 as a prognostic and therapeutic biomarker in ovarian cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; BREAST-CANCER; SIGNALING PATHWAYS; FALLOPIAN-TUBE; ADVANCED-STAGE; GROWTH; EXPRESSION; CARCINOMA; ADENOCARCINOMA; PROLIFERATION AB High-throughput genomic technologies have identified biomarkers and potential therapeutic targets for ovarian cancer. Comprehensive functional validation studies of the biological and clinical implications of these biomarkers are needed to advance them toward clinical use. Amplification of chromosomal region 5q31-5q35.3 has been used to predict poor prognosis in patients with advanced stage, high-grade serous ovarian cancer. In this study, we further dissected this large amplicon and identified the overexpression of FGF18 as an independent predictive marker for poor clinical outcome in this patient population. Using cell culture and xenograft models, we show that FGF18 signaling promoted tumor progression by modulating the ovarian tumor aggressiveness and microenvironrnent. FGF18 controlled migration, invasion, and tumorigenicity of ovarian cancer cells through NF-kappa B activation, which increased the production of oncogenic cytokines and chemokines. This resulted in a tumor microenvironment characterized by enhanced angiogenesis and augmented tumor-associated macrophage infiltration and M2 polarization. Tumors from ovarian cancer patients had increased FGF18 expression levels with microvessel density and M2 macrophage infiltration, confirming our in vitro results. These findings demonstrate that FGF18 is important for a subset of ovarian cancers and may serve as a therapeutic target. C1 [Wei, Wei; Kim, Sung-hoon; Mohapatra, Gayatry; Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Gynecol Oncol,Ctr Canc Res, Boston, MA USA. [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kim, Sung-hoon] Yonsei Univ, Coll Med, Seoul, South Korea. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Ctr Canc Res, YAW 9-072, Boston, MA 02114 USA. EM mbirrer@partners.org RI WEI, WEI/E-3919-2015; OI WEI, WEI/0000-0002-2315-3558 FU NIH [RC4CA156551, 1R01CA142832, R01CA169200, 1U01CA152990, R01CA133057]; MD Anderson Ovarian Cancer SPORE grant [P50 CA083639]; Julie Fund FX The financial support of research grants to M.J. Birrer and S.C. Mok is gratefully acknowledged: NIH grant RC4CA156551 (to M.J. Birrer), NIH grant 1R01CA142832 (to M.J. Birrer), NIH grant R01CA169200 (to M.J. Birrer), NIH grant 1U01CA152990 (to M.J. Birrer), The Julie Fund (to M.J. Birrer), NIH grant R01CA133057 (to S.C. Mok), and the MD Anderson Ovarian Cancer SPORE grant P50 CA083639 (to S.C. Mok). NR 45 TC 20 Z9 20 U1 0 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2013 VL 123 IS 10 BP 4435 EP 4448 DI 10.1172/JCI70625 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 231UE UT WOS:000325443100037 PM 24018557 ER PT J AU Vahdat, LT Vrdoljak, E Gomez, H Li, RK Bosserman, L Sparano, JA Baselga, J Mukhopadhyay, P Valero, V AF Vahdat, Linda T. Vrdoljak, Eduard Gomez, Henry Li, Rubi Khaw Bosserman, Linda Sparano, Joseph A. Baselga, Jose Mukhopadhyay, Pralay Valero, Vicente TI Efficacy and safety of ixabepilone plus capecitabine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Ixabepilone; Capecitabine; Elderly patients; Metastatic breast cancer ID PHASE-III; CHEMOTHERAPY; RESISTANT; SURVIVAL AB Objectives: Data on chemotherapy regimens in elderly patients with metastatic breast cancer (MBC) are limited. The aim of this retrospective pooled analysis was to determine efficacy and safety of ixabepilone plus capecitabine versus capecitabine alone in patients with MBC aged 265 years. Materials and Methods: A total of 1973 patients with MBC previously treated with or resistant to anthracyclines and taxanes were randomized in two open-label, multinational, phase 3 studies (study 046 and study 048). Patients received ixabepilone (40 mg/m(2) as a 3-hour intravenous infusion every 3 weeks) plus oral capecitabine (1000 mg/m2 administered twice each day), or capecitabine alone (1250 mg/m2 twice each day). Results: In total, 251 randomized patients were aged 265 years (ixabepilone plus capecitabine, n = 116; capecitabine monotherapy, n = 135). Efficacy results were consistent in patients aged <65 and >= 65 years with respect to the observed improvement in progression-free survival and objective response rate with ixabepilone plus capecitabine compared with capecitabine alone. No significant differences in overall survival between arms were observed for either subgroup. In the ixabepilone plus capecitabine arm, grade 3/4 hematologic adverse events (AEs) were similar in both subgroups except leukopenia and febrile neutropenia, which had a higher incidence in patients aged >= 65 years. The majority of grade 3/4 nonhematologic AEs were similar in the two subgroups, including fatigue, peripheral sensory neuropathy, and hand-foot syndrome. Conclusion: The combination of ixabepilone plus capecitabine maintains its efficacy in elderly patients with anthracycline and taxane pretreated MBC, with a similar safety profile to patients aged <65 years. (C) 2013 Published by Elsevier Ltd. C1 [Vahdat, Linda T.] Weill Cornell Med Coll, New York, NY USA. [Vrdoljak, Eduard] Klin Bolnica Split, Split, Croatia. [Gomez, Henry] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Li, Rubi Khaw] St Lukes Med Ctr, Quezon City, Philippines. [Bosserman, Linda] Wilshire Oncol, Pomona, CA USA. [Sparano, Joseph A.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Baselga, Jose] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Mukhopadhyay, Pralay] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Valero, Vicente] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Vahdat, LT (reprint author), Weill Cornell Med Coll, Iris Cantor Breast Ctr, New York, NY USA. EM ltv2001@med.cornell.edu OI Vahdat, Linda/0000-0002-3522-7382; Gomez, Henry/0000-0003-2660-1843 FU Bristol-Myers Squibb FX The authors wish to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support. Neither Bristol-Myers Squibb nor StemScientific influenced content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript. NR 16 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD OCT PY 2013 VL 4 IS 4 BP 346 EP 352 DI 10.1016/j.jgo.2013.07.006 PG 7 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 235QL UT WOS:000325735700008 PM 24472478 ER PT J AU Mandelblatt, JS Makgoeng, SB Luta, G Hurria, A Kimmick, G Isaacs, C Tallarico, M Barry, WT Pitcher, B Winer, EP Hudis, C Cohen, HJ Muss, HB AF Mandelblatt, Jeanne S. Makgoeng, Solomon B. Luta, Gheorghe Hurria, Arti Kimmick, Gretchen Isaacs, Claudine Tallarico, Michelle Barry, William T. Pitcher, Brandy Winer, Eric P. Hudis, Clifford Cohen, Harvey J. Muss, Hyman B. TI A planned, prospective comparison of short-term quality of life outcomes among older patients with breast cancer treated with standard chemotherapy in a randomized clinical trial vs. an observational study: CALGB #49907 and #369901 SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Older patients; Breast cancer; Chemotherapy; Quality of Life; Randomized clinical trials; Observational studies ID ADJUVANT CHEMOTHERAPY; WOMEN; QUESTIONNAIRE; RELIABILITY; CARCINOMA; SCORES AB Objectives: Patients >= 65 years old ("older") are often not included in randomized clinical trials (RCT), but when they are, care in an RCT might improve quality of life (QoL). We conducted a prospective comparison of QoL among older women receiving standard chemotherapy from the same cooperative group physicians in an RCT vs. an observational study ("off-trial"). Methods: Older women with invasive, non-metastatic breast cancer (n = 150 RCT; 530 off-Mal) were included. Linear mixed-effects models tested associations between chemotherapy on-vs.off-trial and changes in EORTC (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire) QoL scores over 24 months, controlling for pre-treatment QoL, age, education, tumor factors, comorbidity, and other covariates. Results: Anthracycline regimens were used by 58% of women treated on-trial vs. 54% of those treated off-trial. Women in the RCT reported an adjusted mean increase of 13.7 points (95% CI 10.2, 17.1) in global QoL at 24 months (vs. mid-treatment), while women treated off-trial had only an adjusted improvement of 7.0 points (95% CI 3.5, 10.4; p = .007 for difference in mean changes). Women in the RCT had significantly greater improvement in emotional function than those treated off-trial, controlling for baseline; they also had greater reductions in therapy side effects and fatigue at 24 months than women off-trial, controlling for covariates. Conclusion: There may be different QoL trajectories for older women undergoing breast cancer chemotherapy on-vs. off-trial. If confirmed, the results suggest that the extra monitoring and communication within an RGT could provide the infrastructure for interventions to address symptoms and improve QoL for the growing older cancer population. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Mandelblatt, Jeanne S.; Makgoeng, Solomon B.; Tallarico, Michelle] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Mandelblatt, Jeanne S.; Makgoeng, Solomon B.; Tallarico, Michelle] Lombardi Canc Ctr, Canc Prevent & Control Program, Washington, DC USA. [Luta, Gheorghe] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20007 USA. [Luta, Gheorghe] Lombardi Canc Ctr, Washington, DC USA. [Hurria, Arti] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Los Angeles, CA USA. [Kimmick, Gretchen] Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA. [Isaacs, Claudine] Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. [Isaacs, Claudine] Lombardi Canc Ctr, Breast Canc Program, Washington, DC USA. [Barry, William T.; Pitcher, Brandy] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Barry, William T.; Pitcher, Brandy] Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. [Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hudis, Clifford] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Cohen, Harvey J.] Duke Univ, Dept Med, Durham, NC USA. [Cohen, Harvey J.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. [Muss, Hyman B.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Mandelblatt, JS (reprint author), Lombardi Comprehens Canc Ctr, 3300 Whitehaven Blvd,Suite 4100, Washington, DC 20007 USA. EM mandelbj@georgetown.edu OI Luta, George/0000-0001-9013-2207; Luta, George/0000-0002-4035-7632 FU Glaxo Smith Kline; Abraxis Bioscience; Celgene FX Dr. Arti Hurria: Seattle Genetics, Amgen Pharmaceuticals and Genentech (Consultant); Glaxo Smith Kline, Abraxis Bioscience, and Celgene (Research Support). NR 26 TC 2 Z9 2 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD OCT PY 2013 VL 4 IS 4 BP 353 EP 361 DI 10.1016/j.jgo.2013.05.004 PG 9 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 235QL UT WOS:000325735700009 PM 24472479 ER PT J AU Roque, DR Cronin, B Robison, K Lopes, V Rizack, T Dizon, DS AF Roque, Dario R. Cronin, Beth Robison, Katina Lopes, Vrishali Rizack, Tina Dizon, Don S. TI The effects of age on treatment and outcomes in women with stages IB1-IIB cervical cancer SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Cervical cancer; Treatment allocation; Elderly ID GYNECOLOGIC-ONCOLOGY-GROUP; PELVIC RADIATION-THERAPY; BREAST-CARCINOMA; ELDERLY-PATIENTS; CONCURRENT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADICAL HYSTERECTOMY; NONCARDIAC SURGERY; COMORBIDITY INDEX; OLDER WOMEN AB Objective: Age may affect the treatment choice and subsequent outcome in elderly patients with cervical cancer. Given the potential for cure with either surgery or chemoradiation in early stage disease, we aimed to determine whether a patient's age influenced treatment received and the ensuing outcome. Materials and Methods: We identified 303 patients with stages IB1-IIB cervical carcinoma treated at our institution between 2000 and 2010, who were divided into two groups based on age at time of diagnosis: <65 and >= 65 years. Adjusted odd ratios were calculated to determine variables associated with treatment received. Single and multivariate Cox proportional hazards modeling were used to estimate hazard ratios (HRs) for variables associated with disease-specific survival. Results: Patients were more commonly <65 years at diagnosis (83% versus 17% >= 65 years). There was no difference between the two groups in terms of tumor histology, stage at presentation, and grade. Women >= 65 years of age were less likely to receive primary surgical management (p = 0.03). Age did not influence disease-specific or all-cause mortality. However, women over 65 years who underwent primary surgery were at significantly increased risk of all-cause mortality compared to younger women (HR 6.53, 95% CI: 2.57-16.6). Conclusions: Age appears to influence treatment received by patients with stages IB1-IIB cervical cancer. Although there was no difference in cancer-specific mortality stratified by type of treatment received, surgery was associated with a 6.5-fold increased risk of all-cause mortality among women 65 years or over. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Roque, Dario R.; Cronin, Beth; Robison, Katina; Rizack, Tina] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Providence, RI 02906 USA. [Roque, Dario R.; Cronin, Beth; Robison, Katina] Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Providence, RI 02906 USA. [Robison, Katina; Rizack, Tina] Women & Infants Hosp Rhode Isl, Program Womens Oncol, Providence, RI 02906 USA. [Rizack, Tina] Women & Infants Hosp Rhode Isl, Dept Med, Providence, RI 02906 USA. [Lopes, Vrishali] Women & Infants Hosp Rhode Isl, Div Researcxh, Providence, RI 02906 USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Med Gynecol Oncol Serv, Boston, MA 02114 USA. RP Roque, DR (reprint author), 101 Dudley St, Providence, RI 02905 USA. EM droque@wihri.org; bcronin@wihri.org; krobison@wihri.org; vlopes@wihri.org; trizack@wihri.org; ddizon@partners.org NR 40 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 EI 1879-4076 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD OCT PY 2013 VL 4 IS 4 BP 374 EP 381 DI 10.1016/j.jgo.2013.07.002 PG 8 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 235QL UT WOS:000325735700012 PM 24472482 ER PT J AU Harper, CM Waters, PM AF Harper, Carl M. Waters, Peter M. TI Acute Idiopathic Blue Finger: Case Report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Achenbach syndrome; blue finger; idiopathic; nonischemic ID ACHENBACHS-SYNDROME; WOMEN AB An acute blue finger is an uncommon but potentially serious finding with a heterogeneous etiology. A rare group of patients will present with acute, atraumatic, nonischemic blue fingers. The clinical course of these patients appears to be benign. We describe the presentation of an otherwise healthy 22-year-old woman with an acute idiopathic blue finger. We highlight the differential diagnoses and evaluation of this rare condition. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved. C1 [Harper, Carl M.; Waters, Peter M.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harper, CM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Wht 535, Boston, MA 02114 USA. EM cmharper@partners.org NR 12 TC 2 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2013 VL 38A IS 10 BP 1980 EP 1982 DI 10.1016/j.jhsa.2013.07.022 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 235TD UT WOS:000325742700016 PM 24021741 ER PT J AU Byrareddy, SN Ayash-Rashkovsky, M Kramer, VG Lee, SJ Correll, M Novembre, FJ Villinger, F Johnson, WE von Gegerfelt, A Felber, BK Ruprecht, RM AF Byrareddy, Siddappa N. Ayash-Rashkovsky, Mila Kramer, Victor G. Lee, Sandra J. Correll, Mick Novembre, Francis J. Villinger, Francois Johnson, Welkin E. von Gegerfelt, Agneta Felber, Barbara K. Ruprecht, Ruth M. TI LIVE ATTENUATED REV-IND NEF-SIV ENHANCES ACQUISITION OF HETEROLOGOUS SIVSME660 IN ACUTELY VACCINATED RHESUS MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Byrareddy, Siddappa N.; Ayash-Rashkovsky, Mila; Kramer, Victor G.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Byrareddy, Siddappa N.; Ayash-Rashkovsky, Mila; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Byrareddy, Siddappa N.; Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Lee, Sandra J.; Correll, Mick] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Correll, Mick] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Novembre, Francis J.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Novembre, Francis J.; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Johnson, Welkin E.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 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 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2013 VL 42 IS 5 MA 5 BP 256 EP 256 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 217BR UT WOS:000324332000011 ER PT J AU Rout, N Else, J Streeck, H Kaur, A AF Rout, Namita Else, Jim Streeck, Hendrik Kaur, Amitinder TI LOSS OF DN T LYMPHOCYTE FUNCTIONALITY IN SIMIAN IMMUNODEFICIENCY VIRUS (SIV)-INFECTED RHESUS MACAQUES BUT NOT SOOTY MANGABEYS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Rout, Namita; Kaur, Amitinder] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Else, Jim] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Streeck, Hendrik] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. [Streeck, Hendrik] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 EI 1600-0684 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2013 VL 42 IS 5 MA 13 BP 259 EP 259 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 217BR UT WOS:000324332000019 ER PT J AU Richardson, BD Hancock, KE Caspary, DM AF Richardson, Ben D. Hancock, Kenneth E. Caspary, Donald M. TI Stimulus-specific adaptation in auditory thalamus of young and aged awake rats SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE stimulus-specific adaptation; medial geniculate body; auditory thalamus; aging; awake animals ID MEDIAL GENICULATE-BODY; DORSAL COCHLEAR NUCLEUS; INFERIOR COLLICULUS; MISMATCH NEGATIVITY; RETICULAR NUCLEUS; CORTEX DEACTIVATION; CORTICAL-NEURONS; AGING AFFECTS; HEARING-LOSS; BRAIN-STEM AB Novel stimulus detection by single neurons in the auditory system, known as stimulus-specific adaptation (SSA), appears to function as a real-time filtering/gating mechanism in processing acoustic information. Particular stimulus paradigms allowing for quantification of a neuron's ability to detect novel or deviant stimuli have been used to examine SSA in the inferior colliculus, medial geniculate body (MGB), and auditory cortex of anesthetized rodents. However, the study of SSA in awake animals is limited to auditory cortex. The present study used individually advanceable tetrodes to record single-unit responses from auditory thalamus (MGB) of awake young adult and aged Fischer Brown Norway (FBN) rats to 1) examine the presence of SSA in the MGB of awake rats and 2) determine whether SSA is altered by aging in MGB. MGB single units in awake FBN rats displayed SSA in response to two stimulus paradigms: the oddball paradigm and a random blocked/interleaved presentation of a set of frequencies. SSA levels were modestly, but nonsignificantly, increased in the nonlemniscal regions of the MGB and at lower stimulus intensities, where 27 of 57 (47%) young adult MGB units displayed SSA. The present findings provide the initial description of SSA in the MGB of awake rats and support SSA as being qualitatively independent of arousal level or anesthetized state. Finally, contrary to previous studies in auditory cortex of anesthetized rats, MGB units in aged rats showed SSA levels indistinguishable from SSA levels in young adult rats, suggesting that SSA in MGB was not impacted by aging in an awake preparation. C1 [Richardson, Ben D.; Caspary, Donald M.] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA. [Hancock, Kenneth E.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Hancock, Kenneth E.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Caspary, DM (reprint author), So Illinois Univ, Sch Med, Dept Pharmacol, POB 19629, Springfield, IL 62794 USA. EM dcaspary@siumed.edu RI Richardson, Ben/B-2922-2012; OI Richardson, Benjamin/0000-0003-0403-4956 FU National Institute on Deafness and Other Communication Disorders [DC-00151] FX These studies were supported by National Institute on Deafness and Other Communication Disorders Grant DC-00151. NR 61 TC 10 Z9 10 U1 0 U2 5 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 OCT PY 2013 VL 110 IS 8 BP 1892 EP 1902 DI 10.1152/jn.00403.2013 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 236QU UT WOS:000325815000015 PM 23904489 ER PT J AU Agnihotri, S Venna, N AF Agnihotri, Shruti Venna, Nagagopal TI Atypical neurologic complications of varicella zoster virus SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on NeuroVirology CY OCT 29-NOV 02, 2013 CL Washington, DC C1 [Agnihotri, Shruti; Venna, Nagagopal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM sagnihot@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2013 VL 19 SU 1 MA P2 BP S1 EP S2 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 236EM UT WOS:000325777200003 ER PT J AU Byrareddy, S Thorat, S Sharma, P Hemashettar, GH Matsuda, K Hirsch, V Girolami, U Novembre, F Villinger, F Ruprecht, R AF Byrareddy, Siddappa Thorat, Swati Sharma, Prachi Hemashettar, Girish Hemashettar Matsuda, Kenta Hirsch, Vanessa Girolami, Umberto Novembre, Francis Villinger, Francois Ruprecht, Ruth TI Macrophage/microglia lineage-related R5-tropic simian-human immunodeficiency viruses as tools to induce and study HAND SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on NeuroVirology CY OCT 29-NOV 02, 2013 CL Washington, DC C1 [Byrareddy, Siddappa; Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Byrareddy, Siddappa; Thorat, Swati; Hemashettar, Girish Hemashettar; Ruprecht, Ruth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Byrareddy, Siddappa; Thorat, Swati; Hemashettar, Girish Hemashettar; Ruprecht, Ruth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sharma, Prachi; Novembre, Francis; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Matsuda, Kenta; Hirsch, Vanessa] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD USA. [Girolami, Umberto] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM siddappa.n.byrareddy@emory.edu 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 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2013 VL 19 SU 1 MA P34 BP S17 EP S17 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 236EM UT WOS:000325777200035 ER PT J AU Campbell, JH Ratai, EM Autissier, P MacLean, AG Renner, NA Nolan, DJ Miller, AD Westmoreland, SV Gonzalez, RG Burdo, TH Williams, KC AF Campbell, Jennifer H. Ratai, Eva-Maria Autissier, Patrick MacLean, Andrew G. Renner, Nicole A. Nolan, David J. Miller, Andrew D. Westmoreland, Susan V. Gonzalez, R. Gilberto Burdo, Tricia H. Williams, Kenneth C. TI Tysabri Treatment Suppresses Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on NeuroVirology CY OCT 29-NOV 02, 2013 CL Washington, DC C1 [Campbell, Jennifer H.; Autissier, Patrick; Burdo, Tricia H.; Williams, Kenneth C.] Boston Coll, Chestnut Hill, MA 02167 USA. [Ratai, Eva-Maria; Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Nolan, David J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. EM jennifer.campbell.2@bc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2013 VL 19 SU 1 MA P36 BP S18 EP S18 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 236EM UT WOS:000325777200037 ER PT J AU Bianchi, MT Williams, KL Mckinney, S Ellenbogen, JM AF Bianchi, Matt T. Williams, Kathryn L. Mckinney, Scott Ellenbogen, Jeffrey M. TI The subjective-objective mismatch in sleep perception among those with insomnia and sleep apnea SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE misperception; paradoxical; self-report; subjective ID STATE MISPERCEPTION; TIME-ESTIMATION; LONG-TERM; DURATION; ADULTS; METAANALYSIS; VARIABILITY; PERFORMANCE; SUFFERERS; ONSET AB The diagnosis and management of insomnia relies primarily on clinical history. However, patient self-report of sleep-wake times may not agree with objective measurements. We hypothesized that those with shallow or fragmented sleep would under-report sleep quantity, and that this might account for some of the mismatch. We compared objective and subjective sleep-wake times for 277 patients who underwent diagnostic polysomnography. The group included those with insomnia symptoms (n=92), obstructive sleep apnea (n=66) or both (n=119). Mismatch of wake duration was context dependent: all three groups overestimated sleep latency but underestimated wakefulness after sleep onset. The insomnia group underestimated total sleep time by a median of 81min. However, contrary to our hypothesis, measures of fragmentation (N1, arousal index, sleep efficiency, etc.) did not correlate with the subjective sleep duration estimates. To unmask a potential relationship between sleep architecture and subjective duration, we tested three hypotheses: N1 is perceived as wake; sleep bouts under 10min are perceived as wake; or N1 and N2 are perceived in a weighted fashion. None of these hypotheses exposed a match between subjective and objective sleep duration. We show only modest performance of a Naive Bayes Classifier algorithm for predicting mismatch using clinical and polysomnographic variables. Subjective-objective mismatch is common in patients reporting insomnia symptoms. We conclude that mismatch was not attributable to commonly measured polysomnographic measures of fragmentation. Further insight is needed into the complex relationships between subjective perception of sleep and conventional, objective measurements. C1 [Bianchi, Matt T.; Williams, Kathryn L.; Mckinney, Scott; Ellenbogen, Jeffrey M.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Bianchi, Matt T.; Ellenbogen, Jeffrey M.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org OI Williams, Kathryn/0000-0002-4266-7693 FU Department of Neurology, Massachusetts General Hospital; Harvard Catalyst KL2 Medical Research Investigator Fellowship; Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology Beth Israel Deaconess Medical Center; Pfizer, Inc.; Merck Co. FX The authors thank Drs Catherine Chu, Elizabeth Klerman, Andrew Philips and Wei Wang for valuable suggestions, and Karen Gannon for data assistance. Dr Bianchi received funding from the Department of Neurology, Massachusetts General Hospital, a Harvard Catalyst KL2 Medical Research Investigator Fellowship, and the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology Beth Israel Deaconess Medical Center, in collaboration with Pfizer, Inc. and Merck & Co. Dr Ellenbogen received funding from the Department of Neurology, Massachusetts General Hospital. NR 47 TC 19 Z9 22 U1 3 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD OCT PY 2013 VL 22 IS 5 BP 557 EP 568 DI 10.1111/jsr.12046 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 217CW UT WOS:000324335300010 PM 23521019 ER PT J AU Hanson, LC Ersek, M Lin, FC Carey, TS AF Hanson, Laura C. Ersek, Mary Lin, Feng Chang Carey, Timothy S. TI Outcomes of Feeding Problems in Advanced Dementia in a Nursing Home Population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; nutrition; nursing home ID IMPROVING DECISION-MAKING; RESIDENTS; SURVIVAL; TRIAL AB ObjectivesTo describe quality of care for feeding problems in advanced dementia and probability and predictors of weight loss and mortality. DesignProspective cohort. SettingTwenty-four nursing homes (NHs). ParticipantsNursing home residents with advanced dementia and feeding problems and family surrogates (N=256). MeasurementsFamily reported on quality of feeding care at enrollment and 3months. Chart reviews at enrollment and 3, 6, and 9months provided data on feeding problems, treatments, weight loss of more than 5% in 30days or more than 10% in 6months, and mortality. Organizational variables were obtained from administrator surveys and publically reported data. ResultsResidents with advanced dementia and feeding problems had an average age of 85; 80% had chewing and swallowing problems, 11% weight loss, and 48% poor intake. Family reported feeding assistance of moderate quality; 23% felt the resident received less assistance than needed. Mortality risk was significant; 8% died within 3months, 17% within 6months, and 27% within 9months. Residents with advanced dementia who had stable weight over 3months had a 5.4% rate of significant weight loss and a 2.1% risk of death over the next 3months. Residents with advanced dementia and weight loss over 3months had a 38.9% chance of stabilizing weight over the next 3months but also had a 19.2% chance of dying. Weight loss was the only independent predictor of death. ConclusionWeight loss is a predictor of death in advanced dementia. Treatments can often stabilize weight, but weight loss should be used to trigger discussion of goals of care and treatment options. C1 [Hanson, Laura C.] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC 27599 USA. [Hanson, Laura C.] Univ N Carolina, Ctr Aging & Hlth, Chapel Hill, NC 27599 USA. [Hanson, Laura C.; Carey, Timothy S.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Ersek, Mary] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ersek, Mary] Philadelphia Vet Affairs Med Ctr, Natl PROMISE Ctr, Philadelphia, PA USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Lin, Feng Chang] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. [Carey, Timothy S.] Univ N Carolina, Div Gen Internal Med & Clin Epidemiol, Chapel Hill, NC 27599 USA. RP Hanson, LC (reprint author), Univ N Carolina, Div Geriatr Med, CB 7550, Chapel Hill, NC 27599 USA. EM lhanson@med.unc.edu FU National Institutes of Health National Institute for Nursing Research [R01 NR009826] FX Funding was received from National Institutes of Health National Institute for Nursing Research Grant R01 NR009826: Laura C. Hanson, Mary Ersek, Feng Chang Lin, Timothy S. Carey. NR 18 TC 13 Z9 13 U1 3 U2 18 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 OCT PY 2013 VL 61 IS 10 BP 1692 EP 1697 DI 10.1111/jgs.12448 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233FG UT WOS:000325551500007 PM 24083403 ER PT J AU Huang, DL Chan, KCG Young, BA AF Huang, Deborah L. Chan, Kwun Chuen Gary Young, Bessie A. TI Poor Oral Health and Quality of Life in Older U.S. Adults with Diabetes Mellitus SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE health-related quality of life; oral health; diabetes mellitus ID UNITED-STATES; CARE VISITS; COMMUNITY; DISEASE AB ObjectiveTo determine the association between health-related quality of life (HRQOL) and oral health in older U.S. adults with diabetes mellitus (DM). DesignCross-sectional. SettingData from the U.S. Behavioral Risk Factor Surveillance System 2006, 2008, and 2010. ParticipantsNationally representative sample of 70,363 adults aged 65 and older with DM. ResultsOlder adults with DM were more likely to report permanent tooth loss due to caries or periodontal disease than those without (82.3% vs 74.3%, P<.001) and less likely to receive dental care in the past year (59.0% vs 70.9%, P<.001). Loss of permanent teeth from caries or periodontal disease was associated with 1.25 times greater odds of worse self-rated general health (95% confidence interval (CI)=1.13-1.37). Lack of dental care in the preceding 12months was associated with 1.34 times greater odds of worse self-rated general health (95% CI=1.25-1.44) than receiving dental care in the preceding 12months. Poor dentition and longer time since last dental visit were associated with more physically unhealthy days. ConclusionsPoor dentition and lack of dental care were associated with worse HRQOL in older adults with DM. Further research is needed to determine whether better oral health improves HRQOL in this population. C1 [Huang, Deborah L.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Huang, Deborah L.] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Chan, Kwun Chuen Gary] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence Hosp & Special, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Young, Bessie A.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. RP Huang, DL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S GRECC 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM huangdx@u.washington.edu FU Veterans Affairs (VA) Puget Sound Health Care System in Seattle, Washington; VA Advanced Fellowship in Geriatrics; VA, from the VA Puget Sound Health Care System, Seattle, Washington; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [R01DK079745-01] FX This material is the result of work supported by resources from the Veterans Affairs (VA) Puget Sound Health Care System in Seattle, Washington. Dr. Huang receives salary support from a VA Advanced Fellowship in Geriatrics. Dr. Young receives support from the VA, from the VA Puget Sound Health Care System, Seattle, Washington, and National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Grant R01DK079745-01. NR 28 TC 4 Z9 5 U1 4 U2 17 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 OCT PY 2013 VL 61 IS 10 BP 1782 EP 1788 DI 10.1111/jgs.12452 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233FG UT WOS:000325551500020 PM 24001058 ER PT J AU Lubitz, SA Bauer, KA Benjamin, EJ Besdine, RW Forman, DE Gurol, ME Reddy, VY Singer, DE AF Lubitz, Steven A. Bauer, Kenneth A. Benjamin, Emelia J. Besdine, Richard W. Forman, Daniel E. Gurol, Mahmut E. Reddy, Vivek Y. Singer, Daniel E. TI Stroke Prevention in Atrial Fibrillation in Older Adults: Existing Knowledge Gaps and Areas for Innovation: A Summary of an American Federation for Aging Research Seminar SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE atrial fibrillation; stroke; elderly; prevention ID ORAL ANTICOAGULANTS; CATHETER ABLATION; UNITED-STATES; RISK-FACTORS; WARFARIN; MANAGEMENT; THERAPY; CARE; METAANALYSIS; ASSOCIATION AB Atrial fibrillation (AF) is a common and morbid cardiac arrhythmia that increases in prevalence with advancing age. The risk of ischemic stroke, a primary and disabling hazard of AF, also increases with advancing age. The aging of the population is anticipated to contribute to a rising burden of AF-related morbidity and economic costs, given the close association between the arrhythmia and aging. Recent biological, diagnostic, and therapeutic developments raise hope that AF-related stroke can be largely prevented, yet despite advances in stroke prevention for individuals with AF, numerous scientific and clinical knowledge gaps remain, particularly as these developments are applied to older adults. Given the public health importance of AF-related stroke in elderly adults, a group of clinician-investigators convened on April 5, 2012, to identify promising areas for investigation that may ultimately reduce stroke-related morbidity. This article summarizes the meeting discussion and emphasizes innovative topic areas that may ultimately facilitate the application of novel preventive, diagnostic, and therapeutic insights into the management of older adults with AF. The opinions of those that participated in the meeting limit this report, which may not represent all of the questions that other experts in this field might raise. C1 [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Bauer, Kenneth A.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Bauer, Kenneth A.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Framingham, MA USA. [Besdine, Richard W.] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Besdine, Richard W.] Brown Univ, Alpert Med Sch, Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Forman, Daniel E.] New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gurol, Mahmut E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Reddy, Vivek Y.] Mt Sinai Sch Med, Cardiovasc Inst, Helmsley Electrophysiol Ctr, New York, NY USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM slubitz@partners.org RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Benjamin, Emelia/0000-0003-4076-2336 FU Boston Scientific; Coherex; St. Jude Medical; Daiichi Sankyo; Johnson Johnson; American Heart Association [12FTF11350014]; NIH [1K23H L114724, T32NS048005-08, 5RO1AG026484-08, 5P50 NS051343-08]; National Institutes of Health (NIH) [1R01HL092577, 1R01HL102214]; John A. Hartford Foundation Center of Excellence in Geriatric Medicine Award; Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital; Bristol Meyers Squibb; Pfizer; [1RC2HL101589] FX The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Kenneth A. Bauer is a consultant for Bayer Healthcare, Janssen Pharmaceuticals, BMS, Pfizer, and Boehringer Ingelheim. Vivek Reddy is a consultant for and has received funds from Boston Scientific, Coherex, and St. Jude Medical. Daniel E. Singer has received grants from Daiichi Sankyo and Johnson & Johnson and is a consultant to Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi Sankyo, Johnson & Johnson, and Pfizer.; Dr. Lubitz received supported from the American Heart Association (12FTF11350014) and NIH (1K23H L114724). Dr. Benjamin receives National Institutes of Health (NIH) support from 1R01HL092577 and 1R01HL102214. Dr. Gurol receives NIH support from T32NS048005-08, 5RO1AG026484-08, and 5P50 NS051343-08. Dr. Besdine is supported by a John A. Hartford Foundation Center of Excellence in Geriatric Medicine Award. Dr. Singer received support from 1RC2HL101589 and from the Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital. American Federation for Aging Research and unrestricted educational grants from Bristol Meyers Squibb and Pfizer. NR 34 TC 8 Z9 8 U1 0 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 OCT PY 2013 VL 61 IS 10 BP 1798 EP 1803 DI 10.1111/jgs.12456 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233FG UT WOS:000325551500023 PM 24083473 ER PT J AU Prabhakar, AM Harvey, HB Oklu, R AF Prabhakar, Anand M. Harvey, H. Benjamin Oklu, Rahmi TI Thirty-Day Hospital Re-admissions: A Metric that Matters SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID READMISSIONS-REDUCTION PROGRAM; AORTIC-ANEURYSM REPAIR; MEDICARE BENEFICIARIES; FOLLOW-UP; SURGERY; RISK; CARE; COMPLICATIONS; EMBOLIZATION; OUTCOMES C1 [Prabhakar, Anand M.; Harvey, H. Benjamin; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging, Boston, MA 02114 USA. [Prabhakar, Anand M.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging, 55 Fruit St,GRB-290A, Boston, MA 02114 USA. EM roklu@partners.org NR 28 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2013 VL 24 IS 10 BP 1509 EP 1511 DI 10.1016/j.jvir.2013.06.005 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 231TW UT WOS:000325442300011 PM 24070506 ER PT J AU Christov, M Juppnerr, H AF Christov, Marta Jueppnerr, Harald TI Dietary phosphate: the challenges of exploring its role in FGF23 regulation SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID HYPERPHOSPHATEMIA; CKD AB Fibroblast growth factor 23 (FGF23) is an important regulator of phosphate homeostasis, yet efforts to control its circulating levels by manipulating dietary phosphate intake in humans and animals with normal or impaired kidney function have yielded conflicting results. In the study by Zhang et al., severe phosphate restriction in a genetic mouse model of progressive kidney dysfunction failed to cause a uniform FGF23 reduction, again highlighting the complexity of FGF23 regulation. C1 [Christov, Marta; Jueppnerr, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Christov, Marta; Jueppnerr, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Christov, Marta] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Jueppnerr, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Juppnerr, H (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, Thier 7057,50 Blossom St, Boston, MA 02114 USA. EM hjueppner@partners.org FU NIDDK NIH HHS [K08 DK093608] NR 10 TC 1 Z9 1 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2013 VL 84 IS 4 BP 639 EP 641 DI 10.1038/ki.2013.198 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 229BX UT WOS:000325237900002 PM 24080872 ER PT J AU Sise, ME Courtwright, AM Channick, RN AF Sise, Meghan E. Courtwright, Andrew M. Channick, Richard N. TI Pulmonary hypertension in patients with chronic and end-stage kidney disease SO KIDNEY INTERNATIONAL LA English DT Review DE cardiovascular disease; chronic kidney disease; echocardiography; ESRD; left ventricular hypertrophy; pulmonary ID CHRONIC-RENAL-FAILURE; CONGESTIVE-HEART-FAILURE; CONTINUOUS INTRAVENOUS EPOPROSTENOL; ENDOTHELIN-RECEPTOR ANTAGONIST; CONNECTIVE-TISSUE DISEASE; NITRIC-OXIDE PRODUCTION; HEMODIALYSIS-PATIENTS; ARTERIAL-HYPERTENSION; ARTERIOVENOUS-FISTULA; CONTROLLED-TRIAL AB Pulmonary hypertension is defined as a mean pulmonary artery pressure >= 25 mm Hg and is a recently recognized complication of chronic kidney disease and end-stage renal disease. There is significant epidemiological overlap with kidney disease and the underlying causes of World Health Organization group 1-4 pulmonary hypertension (pulmonary arteriopathy, left heart disease, chronic pulmonary disease, and chronic thromboembolic disease, respectively). In addition, an entity of 'unexplained pulmonary hypertension,' group 5, in patients with chronic kidney disease and end-stage renal disease has emerged, with prevalence estimates of 30-50%. The pathogenesis of pulmonary hypertension in this population is due to alterations in endothelial function, increased cardiac output, and myocardial dysfunction leading to elevated left heart filling pressure, with recent data suggesting that left heart dysfunction may account for the vast majority of pulmonary hypertension in patients with kidney disease. Pulmonary hypertension is an independent predictor of increased mortality in patients on dialysis and those undergoing kidney transplantation. This review summarizes what is known about the epidemiology, pathogenesis, transplantation outcomes, mortality, and treatment of pulmonary hypertension in patients with chronic kidney disease and end-stage renal disease. C1 [Sise, Meghan E.] Columbia Univ, Med Ctr, Dept Med, Div Nephrol, New York, NY 10027 USA. [Courtwright, Andrew M.] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. [Channick, Richard N.] Massachusetts Gen Hosp, Dept Med, Div Pulm Crit Care, Boston, MA 02114 USA. RP Sise, ME (reprint author), Columbia Univ, Med Ctr, Dept Med, Div Nephrol, PH4-435,630 West 168th St, New York, NY 10027 USA. EM Mes2128@co1umbia.edu FU Actelion Pharmaceuticals; Ikaria FX RNC received research grants from Actelion Pharmaceuticals and Ikaria. NR 114 TC 24 Z9 26 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2013 VL 84 IS 4 BP 682 EP 692 DI 10.1038/ki.2013.186 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 229BX UT WOS:000325237900010 PM 23739239 ER PT J AU Christov, M Waikar, SS Pereira, RC Havasi, A Leaf, DE Goltzman, D Pajevic, PD Wolf, M Juppner, H AF Christov, Marta Waikar, Sushrut S. Pereira, Renata C. Havasi, Andrea Leaf, David E. Goltzman, David Pajevic, Paola D. Wolf, Myles Jueppner, Harald TI Plasma FGF23 levels increase rapidly after acute kidney injury SO KIDNEY INTERNATIONAL LA English DT Article DE AKI; fibroblast growth factor 23; phosphate; PTH; vitamin D ID GROWTH-FACTOR 23; DOMINANT HYPOPHOSPHATEMIC RICKETS; VITAMIN-D METABOLISM; STAGE RENAL-DISEASE; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; PHOSPHATE HOMEOSTASIS; PERITONEAL-DIALYSIS; TARGETED ABLATION; BONE TURNOVER AB Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs, we used a murine folic acid-induced nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 h of AKI, with an 18-fold increase at 24 h. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or the vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 h following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice, this increase is independent of established modulators of FGF23 secretion. C1 [Christov, Marta; Pajevic, Paola D.; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Christov, Marta; Pajevic, Paola D.; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Christov, Marta; Wolf, Myles] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Waikar, Sushrut S.; Leaf, David E.] Brigham & Womens Hosp, Div Renal Med, Boston, MA 02115 USA. [Pereira, Renata C.] Univ Calif Los Angeles, Sch Med, Div Pediat Nephrol, Los Angeles, CA USA. [Havasi, Andrea] Boston Med Ctr, Div Nephrol, Boston, MA USA. [Goltzman, David] McGill Univ, Calcium Res Lab, Div Endocrinol, Montreal, PQ, Canada. [Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02115 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM hjueppner@partners.org FU NIH [K08 DK93608, R01DK093574, U01DK085660]; subproject IV [PO1 DK11794] FX This work was supported by grants from the NIH; K08 DK93608 to MC, R01DK093574 and U01DK085660 to SW, and by PO1 DK11794, subproject IV to Hi. MC would like to thank Drs RI Thadhani and JT Potts, Jr for their invaluable support and A Maeda and B Yu for technical assistance. NR 63 TC 40 Z9 40 U1 0 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2013 VL 84 IS 4 BP 776 EP 785 DI 10.1038/ki.2013.150 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 229BX UT WOS:000325237900019 PM 23657144 ER PT J AU Estrella, MM Wyatt, CM Pearce, CL Li, M Shlipak, MG Aouizerat, BE Gustafson, D Cohen, MH Gange, SJ Kao, WHL Parekh, RS AF Estrella, Michelle M. Wyatt, Christina M. Pearce, C. Leigh Li, Man Shlipak, Michael G. Aouizerat, Bradley E. Gustafson, Deborah Cohen, Mardge H. Gange, Stephen J. Kao, W. H. Linda Parekh, Rulan S. TI Host APOL1 genotype is independently associated with proteinuria in HIV infection SO KIDNEY INTERNATIONAL LA English DT Article DE genetic renal disease; HIV; kidney disease; proteinuria ID STAGE RENAL-DISEASE; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; GENOME-WIDE ASSOCIATION; WOMENS INTERAGENCY HIV; KIDNEY-DISEASE; AFRICAN-AMERICANS; ALLOGRAFT SURVIVAL; RISK; VARIANTS; GENE AB Proteinuria is associated with adverse clinical outcomes in HIV infection. Here we evaluated whether APOL1 risk alleles, previously associated with advanced kidney disease, are independently associated with proteinuria in HIV infection in a cross-sectional study of HIV-infected women in the Women's Interagency HIV Study. We estimated the percent difference in urine protein excretion and odds of proteinuria (>= 200 mg/g) associated with two versus one or no APOL1 risk allele using linear and logistic regression, respectively. Of 1285 women successfully genotyped, 379 carried one and 80 carried two risk alleles. Proteinuria was present in 124 women, 78 of whom had proteinuria confirmed on a second sample. In women without prior AIDS, two risk alleles were independently associated with a 69% higher urine protein excretion (95% confidence interval (Cl): 36, 108) and five-fold higher odds of proteinuria (95% CI: 2.45, 10.37) as compared with one or no risk allele. No association was found in women with prior AIDS. Analyses in which women with impaired kidney function were excluded and proteinuria was confirmed by a second urine sample yielded similar estimates. Thus, APOL1 risk alleles are associated with significant proteinuria in HIV-infected persons without prior clinical AIDS, independent of clinical factors traditionally associated with proteinuria. Trials are needed to determine whether APOL1 genotyping identifies individuals who could benefit from earlier intervention to prevent overt renal disease. C1 [Estrella, Michelle M.; Kao, W. H. Linda; Parekh, Rulan S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA. [Wyatt, Christina M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Pearce, C. Leigh] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Li, Man; Gange, Stephen J.; Kao, W. H. Linda; Parekh, Rulan S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Aouizerat, Bradley E.] Univ Calif San Francisco, Dept Physiol Nursing, Inst Human Genet, San Francisco, CA USA. [Gustafson, Deborah] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA. [Gustafson, Deborah] Univ Gothenburg, Sahlgrenska Acad, Neuropsychiat Epidemiol Unit, Sect Psychiat & Neurochem, Gothenburgh, Sweden. [Cohen, Mardge H.] Rush Univ, Med Ctr, Cook Cty Hlth & Hosp Syst, Dept Med, Chicago, IL 60612 USA. [Parekh, Rulan S.] Univ Toronto, Hosp Sick Children, Univ Hlth Network, Toronto, ON M5G 1X8, Canada. RP Estrella, MM (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, 1830 E Monument St,Suite 416, Baltimore, MD 21205 USA. EM mestrel1@jhmi.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Diabetes and Digestive and Kidney Diseases [1 K23DK08131]; National Kidney Foundation of Maryland; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1 K23DK08131 to MME) and through a Mini-Grant provided by the National Kidney Foundation of Maryland (to MME). Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange). The WINS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant number UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 39 TC 12 Z9 12 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2013 VL 84 IS 4 BP 834 EP 840 DI 10.1038/ki.2013.203 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 229BX UT WOS:000325237900026 PM 23715117 ER PT J AU Harb, JG Neviani, P Chyla, BJ Ellis, JJ Ferenchak, GJ Oaks, JJ Walker, CJ Hokland, P Roy, DC Caligiuri, MA Marcucci, G Huettner, CS Perrotti, D AF Harb, J. G. Neviani, P. Chyla, B. J. Ellis, J. J. Ferenchak, G. J. Oaks, J. J. Walker, C. J. Hokland, P. Roy, D. C. Caligiuri, M. A. Marcucci, G. Huettner, C. S. Perrotti, D. TI Bcl-xL anti-apoptotic network is dispensable for development and maintenance of CML but is required for disease progression where it represents a new therapeutic target SO LEUKEMIA LA English DT Article DE CML blast crisis; Bcl-xL; ABT-263; ABT-737; PP242 ID CHRONIC MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW MICROENVIRONMENT; TYROSINE KINASE INHIBITORS; HEMATOPOIETIC STEM-CELLS; MIMETIC ABT-737 TARGETS; BLAST-CRISIS CML; BCR/ABL LEUKEMOGENESIS; DRUG-RESISTANCE; DOWN-REGULATION AB The dismal outcome of blast crisis chronic myelogenous leukemia (CML-BC) patients underscores the need for a better understanding of the mechanisms responsible for the development of drug resistance. Altered expression of the anti-apoptotic Bcl-xL has been correlated with BCR-ABL leukemogenesis; however, its involvement in the pathogenesis and evolution of CML has not been formally demonstrated yet. Thus, we generated an inducible mouse model in which simultaneous expression of p210-BCRABL1 and deletion of bcl-x occurs within hematopoietic stem and progenitor cells. Absence of Bcl-xL did not affect development of the chronic phase-like myeloproliferative disease, but none of the deficient mice progressed to an advanced phenotype, suggesting the importance of Bcl-xL in survival of progressing early progenitor cells. Indeed, pharmacological antagonism of Bcl-xL, with ABT263, combined with PP242-induced activation of BAD markedly augmented apoptosis of CML-BC cell lines and primary CD34(+) progenitors but not those from healthy donors, regardless of drug resistance induced by bone marrow stromal cell-generated signals. Moreover, studies in which BAD or Bcl-xL expression was molecularly altered strongly support their involvement in ABT263/PP242-induced apoptosis of CML-BC progenitors. Thus, suppression of the antiapoptotic potential of Bcl-xL together with BAD activation represents an effective pharmacological approach for patients undergoing blastic transformation. C1 [Harb, J. G.; Neviani, P.; Ellis, J. J.; Ferenchak, G. J.; Oaks, J. J.; Walker, C. J.; Caligiuri, M. A.; Marcucci, G.; Perrotti, D.] Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH USA. [Harb, J. G.; Chyla, B. J.; Huettner, C. S.] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA. [Neviani, P.; Caligiuri, M. A.; Marcucci, G.; Perrotti, D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Hokland, P.] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark. [Roy, D. C.] Maisonneuve Rosemont Hosp, Dept Hematol Oncol, Montreal, PQ, Canada. [Roy, D. C.] Univ Montreal, Montreal, PQ, Canada. [Caligiuri, M. A.; Marcucci, G.] Dept Internal Med, Columbus, OH USA. [Huettner, C. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. RP Perrotti, D (reprint author), Ohio State Univ, Ctr Comprehens Canc, 892 Biomed Res Tower,460 West 12th Ave, Columbus, OH 43210 USA. EM danilo.perrotti@osumc.edu OI Hokland, Peter/0000-0002-1177-9756 FU NIH [CA095512, CA163800, CA16058, HL-07209]; Fonds de Recherche Quebec Sante-TheCell; Lauri Strauss Leukemia and BloodCenter Research Foundations; Danish Medical Research Council; Danish Cancer Society; Karen Elise Jensen Foundation FX DP is a Scholar of The Leukemia and Lymphoma Society. This work was supported, in part, by NIH Grants CA095512 and CA163800 (DP), CA16058 (OSU-CCC); Fonds de Recherche Quebec Sante-TheCell (DCR); Lauri Strauss Leukemia and BloodCenter Research Foundations (CSH); the Danish Medical Research Council, the Danish Cancer Society and the Karen Elise Jensen Foundation (PH) grants. JGH was supported, in part, by NIH training Grant HL-07209. We thank L. Hennighausen (NIH, Bethesda, MD, USA) for providing Bcl-x f/f mice; H. Albertz and C. Reinbold (FACS Core Facility, Blood Research Institute, Milwaukee, WI, USA) for technical assistance; J. Perrin (OSU Medical Center, Columbus, OH, USA) for helping in procuring CML specimens and S. Lee (OSU Medical Center, Columbus, OH, USA) for editorial assistance. NR 60 TC 7 Z9 8 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD OCT PY 2013 VL 27 IS 10 BP 1996 EP 2005 DI 10.1038/leu.2013.151 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 234KN UT WOS:000325642600006 PM 23670294 ER PT J AU Metzeler, KH Maharry, K Kohlschmidt, J Volinia, S Mrozek, K Becker, H Nicolet, D Whitman, SP Mendler, JH Schwind, S Eisfeld, AK Wu, YZ Powell, BL Carter, TH Wetzler, M Kolitz, JE Baer, MR Carroll, AJ Stone, RM Caligiuri, MA Marcucci, G Bloomfield, CD AF Metzeler, K. H. Maharry, K. Kohlschmidt, J. Volinia, S. Mrozek, K. Becker, H. Nicolet, D. Whitman, S. P. Mendler, J. H. Schwind, S. Eisfeld, A-K Wu, Y-Z Powell, B. L. Carter, T. H. Wetzler, M. Kolitz, J. E. Baer, M. R. Carroll, A. J. Stone, R. M. Caligiuri, M. A. Marcucci, G. Bloomfield, C. D. TI A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia SO LEUKEMIA LA English DT Article DE acute myeloid leukemia; leukemic stem cells; gene expression profiling; prognostication; gene mutations ID PARTIAL TANDEM DUPLICATION; GROUP-B; OLDER PATIENTS; PROGNOSTIC-SIGNIFICANCE; EUROPEAN LEUKEMIANET; MUTATIONS; CANCER; MICE; RECOMMENDATIONS; SURVIVAL AB Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a 'core enriched' (CE) GES, representing 44 genes activated in LCSs, conferred shorter survival in cytogenetically normal (CN) AML. The prognostic impact of the CE GES in the context of other molecular markers, including gene mutations and microRNA (miR) expression alterations, is unknown and its clinical utility is unclear. We studied associations of the CE GES with known molecular prognosticators, miR expression profiles, and outcomes in 364 well-characterized CN-AML patients. A high CE score (CEhigh) associated with FLT3-internal tandem duplication, WT1 and RUNX1 mutations, wild-type CEBPA and TET2, and high ERG, BAALC and miR-155 expression. CEhigh patients had a lower complete remission (CR) rate (P = 0.003) and shorter disease-free (DFS, P < 0.001) and overall survival (OS, P < 0.001) than CElow patients. These associations persisted in multivariable analyses adjusting for other prognosticators (CR, P = 0.02; DFS, P < 0.001; and OS, P < 0.001). CEhigh status was accompanied by a characteristic miR expression signature. Fifteen miRs were upregulated in both younger and older CEhigh patients, including miRs relevant for stem cell function. Our results support the clinical relevance of LSCs and improve risk stratification in AML. C1 [Metzeler, K. H.; Maharry, K.; Kohlschmidt, J.; Volinia, S.; Mrozek, K.; Becker, H.; Nicolet, D.; Whitman, S. P.; Mendler, J. H.; Schwind, S.; Eisfeld, A-K; Wu, Y-Z; Caligiuri, M. A.; Marcucci, G.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Maharry, K.; Kohlschmidt, J.; Nicolet, D.] Mayo Clin, Alliance Clin Trials Oncol Stat & Data Ctr, Rochester, MN USA. [Powell, B. L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Carter, T. H.] Univ Iowa, Iowa City, IA USA. [Wetzler, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kolitz, J. E.] Hofstra North Shore Long Isl Jewish Sch Med, Monter Canc Ctr, Lake Success, NY USA. [Baer, M. R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Carroll, A. J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marcucci, G (reprint author), Ohio State Univ, Ctr Comprehens Canc, 410 Biomed Res Tower,460 West 12th Ave, Columbus, OH 43210 USA. EM guido.marcucci@osumc.edu; clara.bloomfield@osumc.edu RI Metzeler, Klaus/C-2118-2009; Mrozek, Krzysztof/A-3142-2008; OI Metzeler, Klaus/0000-0003-3920-7490; Carter, Thomas/0000-0001-7796-2986; Mendler, Jason/0000-0001-5605-5324; Volinia, Stefano/0000-0003-0910-3893 FU National Cancer Institute [CA101140, CA114725, CA31946, CA33601, CA16058, CA77658, CA129657, CA140158]; Coleman Leukemia Research Foundation; Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation; Pelotonia Fellowship Program; Conquer Cancer Foundation FX This work was supported in part by the National Cancer Institute (CA101140, CA114725, CA31946, CA33601, CA16058, CA77658, CA129657 and CA140158), The Coleman Leukemia Research Foundation, the Deutsche Krebshilfe-Dr Mildred Scheel Cancer Foundation (HB), the Pelotonia Fellowship Program (A-KE) and the Conquer Cancer Foundation (JHM). The CALGB/Alliance institutions, principal investigators and cytogeneticists participating in this study are listed in the Supplementary Information. We thank Donna Bucci and the CALGB/Alliance Leukemia Tissue Bank at The Ohio State University Comprehensive Cancer Center, Columbus, OH, for sample processing and storage services, and Lisa J Sterling, Christine Finks and Colin G Edwards, PhD, for data management. NR 45 TC 22 Z9 22 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD OCT PY 2013 VL 27 IS 10 BP 2023 EP 2031 DI 10.1038/leu.2013.181 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 234KN UT WOS:000325642600009 PM 23765227 ER PT J AU Murphy, DM Bejar, R Stevenson, K Neuberg, D Shi, Y Cubrich, C Richardson, K Eastlake, P Garcia-Manero, G Kantarjian, H Ebert, BL Makrigiorgos, GM AF Murphy, D. M. Bejar, R. Stevenson, K. Neuberg, D. Shi, Y. Cubrich, C. Richardson, K. Eastlake, P. Garcia-Manero, G. Kantarjian, H. Ebert, B. L. Makrigiorgos, G. Mike TI NRAS mutations with low allele burden have independent prognostic significance for patients with lower risk myelodysplastic syndromes SO LEUKEMIA LA English DT Letter ID COLD-PCR; ENRICHMENT; PROGRESSION; CANCER; FLT3 C1 [Murphy, D. M.; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Stevenson, K.; Neuberg, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bejar, R.] UCSD, Moores Canc Ctr, Div Hematol & Oncol, La Jolla, CA USA. [Shi, Y.; Cubrich, C.; Richardson, K.; Eastlake, P.] Transgenomic Inc, Omaha, NE USA. [Garcia-Manero, G.; Kantarjian, H.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Ebert, B. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Murphy, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM bebert@partners.org; mmakrigiorgos@partners.org FU NCI NIH HHS [CA-111994, CA-151164, P01 CA108631, P01-CA108631, P30 CA016672, R21 CA111994, R21 CA151164, R33 CA111994]; NHLBI NIH HHS [R01 HL082945, R01-HL082945]; NIDDK NIH HHS [1K08DK091360, K08 DK091360] NR 15 TC 22 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD OCT PY 2013 VL 27 IS 10 BP 2077 EP 2081 DI 10.1038/leu.2013.160 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 234KN UT WOS:000325642600019 PM 23708912 ER PT J AU Bergstrom, AR Nur, F Davis, DL AF Bergstrom, A. Renee Nur, Filsan Davis, Denise Lynne TI Consider the Personhood of Women Who Experienced Genital Cutting SO MAYO CLINIC PROCEEDINGS LA English DT Letter ID FEMALE CIRCUMCISION; CARE C1 [Bergstrom, A. Renee; Nur, Filsan] Mayo Clin, Rochester, MN USA. [Davis, Denise Lynne] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Bergstrom, AR (reprint author), Mayo Clin, Rochester, MN USA. NR 5 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2013 VL 88 IS 10 BP 1180 EP 1180 DI 10.1016/j.mayocp.2013.08.004 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 232DR UT WOS:000325470800024 PM 24079688 ER PT J AU Warner, JL Yang, P Alterovitz, G AF Warner, Jeremy L. Yang, Peter Alterovitz, Gil TI Reversal of Medical Practices SO MAYO CLINIC PROCEEDINGS LA English DT Letter C1 [Warner, Jeremy L.] Vanderbilt Univ, Nashville, TN 37235 USA. [Yang, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Alterovitz, Gil] Harvard Univ, Sch Med, Boston, MA USA. RP Warner, JL (reprint author), Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. OI Warner, Jeremy/0000-0002-2851-7242 NR 4 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2013 VL 88 IS 10 BP 1182 EP 1183 DI 10.1016/j.mayocp.2013.08.010 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 232DR UT WOS:000325470800027 PM 24079691 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI Michael Servetus: Unorthodox Theologian, Meticulous Cartographer, and Innovative Anatomist SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Steensma, David/0000-0001-5130-9284 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 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2013 VL 88 IS 10 BP E119 EP E120 DI 10.1016/j.mayocp.2012.12.015 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 232DR UT WOS:000325470800002 PM 24079695 ER PT J AU Huskamp, HA Stevenson, DG O'Malley, J Dusetzina, SB Mitchell, SL Zarowitz, BJ Chernew, ME Newhouse, JP AF Huskamp, Haiden A. Stevenson, David G. O'Malley, James Dusetzina, Stacie B. Mitchell, Susan L. Zarowitz, Barbara J. Chernew, Michael E. Newhouse, Joseph P. TI Medicare Part D Plan Generosity and Medication Use Among Dual-eligible Nursing Home Residents SO MEDICAL CARE LA English DT Article DE Part D; plan generosity; nursing home; dual eligible ID LONG-TERM-CARE; PRIOR-AUTHORIZATION POLICIES; ADVERSE DRUG EVENTS; COVERAGE; IMPACT; IMPLEMENTATION; EXPENDITURES; FACILITIES; INHIBITORS; MICHIGAN AB Background:In 2006, dual-eligible nursing home residents were randomly assigned to a Medicare Part D prescription drug plan (PDP). Subsequently, residents not enrolled in qualified plans at the start of the next year were rerandomized. PDPs vary in generosity through differences in medication coverage and utilization management. Therefore, residents' assigned plans may be relatively more or less generous for their particular drugs. The impact of generosity on residents' medication use and health outcomes is unknown.Methods:Using data from 2005 to 2008, we estimated logistic regression models of the impact of coverage and utilization management on the risk for medication changes and gaps in use, hospitalizations, and death among elderly nursing home residents using 1 of 6 selected drug classes, adjusting for patient characteristics.Results:Few current medication users faced noncoverage of their drug (0.4% to 8.7%) or prior authorization or step therapy requirements if the drug was covered (1.1% to 37.4%). After adjusting for individual-level covariates, residents with noncovered drugs were more likely than residents with covered drugs to change medications in most classes studied (eg, for 2006 angiotensin receptor blocker users, the adjusted average probability of medication change was 0.35 when uncovered vs. 0.11 when covered). Those subjected to prior authorization or step therapy were more likely to change in a subset of classes. There were no statistically significant differences in the rates of hospitalization or death after correcting for multiple comparisons.Conclusions:The Part D benefit's special protections for nursing home residents may have ameliorated the health impact of coverage limits on this frail elderly population. C1 [Huskamp, Haiden A.; Stevenson, David G.; Chernew, Michael E.; Newhouse, Joseph P.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [O'Malley, James] Dartmouth Inst, Lebanon, NH USA. [O'Malley, James] Geisel Med Sch Dartmouth, Lebanon, NH USA. [Dusetzina, Stacie B.] Univ N Carolina, Sch Med, Div Gen Med & Clin Epidemiol, Chapel Hill, NC USA. [Dusetzina, Stacie B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Dusetzina, Stacie B.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. [Mitchell, Susan L.] Hebrew SeniorLife, Deaconess Med Ctr, Inst Aging Res, Boston, MA USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Zarowitz, Barbara J.] Omnicare Inc, Livonia, MI USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Kennedy Sch, Cambridge, MA USA. RP Huskamp, HA (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM huskamp@hcp.med.harvard.edu FU National Institute on Aging [AG034085, K01 AG038481, K24AG033640]; National Institute of Mental Health through Harvard Medical School, Department of Health Care Policy [T32MH019733-17]; National Institutes of Mental Health [1RC4MH092717-01]; Amgen; Sanofi-Aventis; Mylan; AbbVie; Astellas; Optimer; CareFirst; Commonwealth Fund; Charles H. Hood Foundation; InHealth; Institute of Medicine; Pfizer Inc.; Robert Wood Johnson Foundation FX Supported by the National Institute on Aging (R01 # AG034085). D. G. S. was supported in part by a training grant from the National Institute on Aging (K01 AG038481). S. L. M. is supported by a mid-career award from the National Institute on Aging (K24AG033640). At the time of this work, S. B. D. was funded by the National Institute of Mental Health through Harvard Medical School, Department of Health Care Policy, T32MH019733-17. A. J. O. was also supported by the National Institutes of Mental Health (1RC4MH092717-01).; J.P.N. is the director of and holds equity in Aetna, which sells Part D plans. B. J. Z. is an employee of Omnicare Inc., and holds Omnicare Inc., stock. She participates in research projects funded by grants from Amgen, Sanofi-Aventis, Mylan, AbbVie, Astellas, and Optimer. M. E. C. reports the following potential conflicts: Research support: CareFirst, NIA, The Commonwealth Fund, Charles H. Hood Foundation, InHealth, Institute of Medicine, Pfizer Inc., Robert Wood Johnson Foundation; Board memberships: Commonwealth Fund Commission of High Performance, Congressional Budget Office, Medicare Payment Advisory Commission, Abbott, FairHealth, Health Research & Educational Trust, National Institute of Health Care Management, CMS Technical Advisory Panel, NC Prevention Partner Advisory Council on Evidence-based Incentives and Benefits, and Massachusetts Medical Society; Consultancy: Massachusetts Medical Society, America's Health Insurance Plans, Abbott, Humana, SEIU, Precision Health Economics, US Chamber of Commerce, and Milliman; LLC Equity: Benefit Based Designs, Value Based Insurance Design Institute, and Value Based Insurance Design Health; Payment for Manuscript Prep/development: Truven Healthcare Analytics, Precision Health Economics, New America Foundation, and London School of Economics; Role as Journal Editor: Health Services Research and American Journal of Managed Care. The remaining authors declare no conflict of interest. NR 41 TC 2 Z9 2 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD OCT PY 2013 VL 51 IS 10 BP 894 EP 900 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 222SI UT WOS:000324751000007 PM 24025658 ER PT J AU Steinman, MA Dimaano, L Peterson, CA Heidenreich, PA Knight, SJ Fung, KZ Kaboli, PJ AF Steinman, Michael A. Dimaano, Liezel Peterson, Carolyn A. Heidenreich, Paul A. Knight, Sara J. Fung, Kathy Z. Kaboli, Peter J. TI Reasons for Not Prescribing Guideline-recommended Medications to Adults With Heart Failure SO MEDICAL CARE LA English DT Article DE guideline adherence; heart failure; drug prescribing; performance measurement ID ELECTRONIC HEALTH RECORDS; CORONARY-ARTERY-DISEASE; QUALITY MEASURES; PRIMARY-CARE; PERFORMANCE; PAY; EXCEPTIONS; MANAGEMENT; VETERANS; BARRIERS AB Background:Little is known about how often contextual factors such as patient preferences and competing priorities impact prescribing of guideline-recommended medications, or about the extent to which these factors are documented in medical records and available to performance measurement systems.Methods:Mixed-methods study of 295 veterans aged 50 years and older in 4 VA health care systems who had systolic heart failure and were not prescribed a -blocker and/or an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker. Reasons for nontreatment were identified from clinic notes and from interviews with 62 primary care clinicians caring for these patients. These reasons were classified using a published taxonomy.Results:Among 295 patients not receiving guideline-recommended drugs for heart failure, chart review identified biomedical reasons for nonprescribing in 42%-58% of patients and contextual reasons in 11%-17%. Clinician interviews identified twice as many reasons for nonprescribing as chart review (mean 1.6 vs. 0.8 reasons per patient, P<0.001). In these interviews, biomedical reasons for nonprescribing were cited in 50%-70% of patients, and contextual reasons in 64%-70%. The most common contextual reasons were comanagement with other clinicians (32%-35% of patients), patient preferences and nonadherence (15%-24%), and clinician belief that the medication is not indicated in the patient (12%-20%).Conclusions:Contextual reasons for not prescribing angiotensin converting enzyme inhibitor / angiotensin-receptor blockers and -blockers are present in two thirds of patients with heart failure who did not receive these medications, yet are poorly documented in medical records. The structure of medical records should be improved to facilitate documentation of contextual reasons for not providing guideline-recommended care. C1 [Steinman, Michael A.; Peterson, Carolyn A.; Fung, Kathy Z.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. [Steinman, Michael A.; Dimaano, Liezel; Peterson, Carolyn A.; Fung, Kathy Z.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Peterson, Carolyn A.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. [Heidenreich, Paul A.] Stanford Univ, Dept Med, Palo Alto VA Hlth Care Syst, Stanford, CA 94305 USA. [Knight, Sara J.] Univ Calif San Francisco, Vet Affairs Off Res & Dev, San Francisco, CA 94143 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Kaboli, Peter J.] Iowa City VA Healthcare Syst, CADRE Ctr, Iowa City, IA USA. [Kaboli, Peter J.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, POB 181G,4150 Clement St, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 06-080-02, CHF QUERI-04-326]; National Institute on Aging; American Federation for Aging Research [1K23-AG030999] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 06-080-02 and CHF QUERI-04-326), and by the National Institute on Aging and the American Federation for Aging Research (1K23-AG030999). The funders had no role in study design, data collection, analysis, interpretation, or the decision to publish this manuscript. NR 28 TC 12 Z9 13 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD OCT PY 2013 VL 51 IS 10 BP 901 EP 907 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 222SI UT WOS:000324751000008 PM 23969589 ER PT J AU Lapham, GT Rubinsky, AD Heagerty, PJ Williams, EC Hawkins, EJ Maynard, C Kivlahan, DR Bradley, KA AF Lapham, Gwen T. Rubinsky, Anna D. Heagerty, Patrick J. Williams, Emily C. Hawkins, Eric J. Maynard, Charles Kivlahan, Daniel R. Bradley, Katharine A. TI Annual Rescreening for Alcohol Misuse Diminishing Returns for Some Patient Subgroups SO MEDICAL CARE LA English DT Article DE alcoholism and addictive behaviors; screening; public health ID RANDOMIZED CONTROLLED-TRIAL; IDENTIFICATION TEST AUDIT; SERVICES-TASK-FORCE; PRIMARY-CARE; VETERANS-AFFAIRS; HEALTH-CARE; PREVENTIVE-SERVICES; HAZARDOUS DRINKING; SCREENING SCORES; USE DISORDER AB Background:Routine alcohol screening is widely recommended, and Medicare now reimburses for annual alcohol screening. Although up to 18% of patients will screen positive for alcohol misuse, the value of annual rescreening for patients who repeatedly screen negative is unknown.Objective:To evaluate the probability of converting to a positive alcohol screen at annual rescreening among VA outpatients who previously screened negative 2-4 times.Research Design:Retrospective cohort study.Subjects:A total of 179,035 VA outpatients (10,588 women) who previously screened negative on 2 and up to 4 consecutive annual alcohol screens and were rescreened the next year.Measures:AUDIT-C alcohol screening scores (range, 0-12) were obtained from electronic medical record data. The probability of converting to a positive screen (scores: men 4; women, 3) at rescreening after 2-4 prior negative screens was evaluated overall and across subgroups based on age, sex, and prior negative screen scores (scores: men, 0-3; women, 0-2).Results:The overall probability of converting to a positive subsequent screen decreased modestly from 3.5% to 1.9% as the number of prior consecutive negative screens increased from 2 to 4, yet varied widely across subgroups based on age, sex, and prior negative screen scores (0.6%-38.7%).Conclusions:The likelihood of converting to a positive screen at annual rescreening is strongly influenced by age, sex, and scaled screening scores on prior negative alcohol screens. Algorithms for the frequency of repeat alcohol screening for patients who repeatedly screen negative should be based on these factors. These results may have implications for other routine behavioral health screenings. C1 [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Maynard, Charles; Kivlahan, Daniel R.; Bradley, Katharine A.] Northwest Ctr Excellence, Hlth Serv Res & Dev HSR&D, Seattle, WA USA. [Lapham, Gwen T.; Rubinsky, Anna D.; Heagerty, Patrick J.; Williams, Emily C.; Maynard, Charles; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.; Bradley, Katharine A.] CESATE, Seattle, WA USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. RP Lapham, GT (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM gwendolyn.lapham@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU VA HSR&D Substance Use Disorders Quality Enhancement Research Initiative (QUERI) [RRP 11-021] FX Supported by VA HSR&D Substance Use Disorders Quality Enhancement Research Initiative (QUERI) RRP 11-021. NR 50 TC 5 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD OCT PY 2013 VL 51 IS 10 BP 914 EP 921 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 222SI UT WOS:000324751000010 PM 23969582 ER PT J AU Miller, CJ Grogan-Kaylor, A Perron, BE Kilbourne, AM Woltmann, E Bauer, MS AF Miller, Christopher J. Grogan-Kaylor, Andrew Perron, Brian E. Kilbourne, Amy M. Woltmann, Emily Bauer, Mark S. TI Collaborative Chronic Care Models for Mental Health Conditions Cumulative Meta-analysis and Metaregression to Guide Future Research and Implementation SO MEDICAL CARE LA English DT Review DE comparative effectiveness research; disease management models; organizational; delivery of health care; integrated; patient-centered care ID RANDOMIZED-CONTROLLED-TRIAL; IMPROVE DEPRESSION CARE; SHARED DECISION-MAKING; DISSEMINATING QUALITY IMPROVEMENT; STARTING ANTIDEPRESSANT TREATMENT; MEDICATION ALGORITHM PROJECT; DISEASE MANAGEMENT PROGRAMS; LONG-TERM EFFECTIVENESS; LATE-LIFE DEPRESSION; BIPOLAR DISORDER AB Objective:Prior meta-analysis indicates that collaborative chronic care models (CCMs) improve mental and physical health outcomes for individuals with mental disorders. This study aimed to investigate the stability of evidence over time and identify patient and intervention factors associated with CCM effects to facilitate implementation and sustainability of CCMs in clinical practice.Methods:We reviewed 53 CCM trials that analyzed depression, mental quality of life (QOL), or physical QOL outcomes. Cumulative meta-analysis and metaregression were supplemented by descriptive investigations across and within trials.Results:Most trials targeted depression in the primary care setting, and cumulative meta-analysis indicated that effect sizes favoring CCM quickly achieved significance for depression outcomes, and more recently achieved significance for mental and physical QOL. Four of 6 CCM elements (patient self-management support, clinical information systems, system redesign, and provider decision support) were common among reviewed trials, whereas 2 elements (health care organization support and linkages to community resources) were rare. No single CCM element was statistically associated with the success of the model. Similarly, metaregression did not identify specific factors associated with CCM effectiveness. Nonetheless, results within individual trials suggest that increased illness severity predicts CCM outcomes.Conclusions:Significant CCM trials have been derived primarily from 4 original CCM elements. Nonetheless, implementing and sustaining this established model will require health care organization support. Although CCMs have typically been tested as population-based interventions, evidence supports stepped care application to more severely ill individuals. Future priorities include developing implementation strategies to support adoption and sustainability of the model in clinical settings while maximizing fit of this multicomponent framework to local contextual factors. C1 [Miller, Christopher J.; Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Miller, Christopher J.; Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Grogan-Kaylor, Andrew; Perron, Brian E.] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Kilbourne, Amy M.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Woltmann, Emily] Washington Univ, Brown Sch, St Louis, MO USA. RP Miller, CJ (reprint author), VA Boston Healthcare Syst, 152M,150 South Huntington Ave, Boston, MA 02130 USA. EM christopher.miller8@va.gov OI Grogan-Kaylor, Andrew/0000-0003-0065-9991 FU NIMH NIH HHS [R01 MH079994] NR 101 TC 16 Z9 16 U1 2 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD OCT PY 2013 VL 51 IS 10 BP 922 EP 930 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 222SI UT WOS:000324751000011 PM 23938600 ER PT J AU Damato, AL Viswanathan, AN Cormack, RA AF Damato, Antonio L. Viswanathan, Akila N. Cormack, Robert A. TI Validation of mathematical models for the prediction of organs-at-risk dosimetric metrics in high-dose-rate gynecologic interstitial brachytherapy SO MEDICAL PHYSICS LA English DT Article DE brachytherapy; predictive; organs at risk; interstitial; HDR ID CERVICAL-CANCER BRACHYTHERAPY; IMAGE; MALIGNANCIES; PARAMETERS AB Purpose: Given the complicated nature of an interstitial gynecologic brachytherapy treatment plan, the use of a quantitative tool to evaluate the quality of the achieved metrics compared to clinical practice would be advantageous. For this purpose, predictive mathematical models to predict the D-2cc of rectum and bladder in interstitial gynecologic brachytherapy are discussed and validated. Methods: Previous plans were used to establish the relationship between D2cc and the overlapping volume of the organ at risk with the targeted area (C0) or a 1-cm expansion of the target area (C1). Three mathematical models were evaluated: D-2cc = alpha*C-1 + beta (LIN); D-2cc = alpha - exp(-beta*C-0) (EXP); and a mixed approach (MIX), where both C-0 and C-1 were inputs of the model. The parameters of the models were optimized on a training set of patient data, and the predictive error of each model (predicted D-2cc - real D-2cc) was calculated on a validation set of patient data. The data of 20 patients were used to perform a K-fold cross validation analysis, with K = 2, 4, 6, 8, 10, and 20. Results: MIX was associated with the smallest mean prediction error <6.4% for an 18-patient training set; LIN had an error <8.5%; EXP had an error <8.3%. Best case scenario analysis shows that an error <= 5% can be achieved for a ten-patient training set with MIX, an error <= 7.4% for LIN, and an error <= 6.9% for EXP. The error decreases with the increase in training set size, with the most marked decrease observed for MIX. Conclusions: The MIX model can predict the D-2cc of the organs at risk with an error lower than 5% with a training set of ten patients or greater. The model can be used in the development of quality assurance tools to identify treatment plans with suboptimal sparing of the organs at risk. It can also be used to improve preplanning and in the development of real-time intraoperative planning tools. (c) 2013 American Association of Physicists in Medicine. C1 [Damato, Antonio L.] Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Damato, AL (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM adamato@partners.org OI Cormack, Robert/0000-0001-5553-9984 NR 15 TC 2 Z9 2 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2013 VL 40 IS 10 AR 101711 DI 10.1118/1.4819946 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 231DT UT WOS:000325394400015 PM 24089901 ER PT J AU Meaney, PM Golnabi, AH Epstein, NR Geimer, SD Fanning, MW Weaver, JB Paulsen, KD AF Meaney, Paul M. Golnabi, Amir H. Epstein, Neil R. Geimer, Shireen D. Fanning, Margaret W. Weaver, John B. Paulsen, Keith D. TI Integration of microwave tomography with magnetic resonance for improved breast imaging SO MEDICAL PHYSICS LA English DT Article DE breast cancer; MRI; microwave tomography; multimodal imaging; specificity enhancement ID INFRARED SPECTRAL TOMOGRAPHY; DIFFUSE OPTICAL SPECTROSCOPY; INITIAL CLINICAL-EXPERIENCE; DIELECTRIC-PROPERTIES; NEOADJUVANT CHEMOTHERAPY; CANCER DETECTION; TISSUE WATER; LARGE-SCALE; HIGH-RISK; IN-VIVO AB Purpose: Breast magnetic resonance imaging is highly sensitive but not very specific for the detection of breast cancer. Opportunities exist to supplement the image acquisition with a more specific modality provided the technical challenges of meeting space limitations inside the bore, restricted breast access, and electromagnetic compatibility requirements can be overcome. Magnetic resonance (MR) and microwave tomography (MT) are complementary and synergistic because the high resolution of MR is used to encode spatial priors on breast geometry and internal parenchymal features that have distinct electrical properties (i.e., fat vs fibroglandular tissue) for microwave tomography. Methods: The authors have overcome integration challenges associated with combining MT with MR to produce a new coregistered, multimodality breast imaging platform-magnetic resonance microwave tomography, including: substantial illumination tank size reduction specific to the confined MR bore diameter, minimization of metal content and composition, reduction of metal artifacts in the MR images, and suppression of unwanted MT multipath signals. Results: MR SNR exceeding 40 dB can be obtained. Proper filtering of MR signals reduces MT data degradation allowing MT SNR of 20 dB to be obtained, which is sufficient for image reconstruction. When MR spatial priors are incorporated into the recovery of MT property estimates, the errors between the recovered versus actual dielectric properties approach 5%. Conclusions: The phantom and human subject exams presented here are the first demonstration of combining MT with MR to improve the accuracy of the reconstructed MT images. (C) 2013 American Association of Physicists in Medicine. C1 [Meaney, Paul M.; Epstein, Neil R.; Fanning, Margaret W.; Paulsen, Keith D.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Golnabi, Amir H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golnabi, Amir H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Geimer, Shireen D.; Weaver, John B.; Paulsen, Keith D.] Dartmouth Coll, Dept Radiol, Geisel Sch Med, Hanover, NH 03755 USA. [Paulsen, Keith D.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Paulsen, Keith D.] Dartmouth Hitchcock Med Ctr, Adv Surg Ctr, Lebanon, NH 03756 USA. RP Meaney, PM (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM paul.meaney@dartmouth.edu FU NIH/NCI [R33-CA102938] FX This work was supported by NIH/NCI grant # R33-CA102938 and the generous donations of Charlotte S. Metcalf and the Telaka Foundation. NR 69 TC 12 Z9 12 U1 1 U2 12 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2013 VL 40 IS 10 AR 103101 DI 10.1118/1.4820361 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 231DT UT WOS:000325394400044 PM 24089930 ER PT J AU Rakvongthai, Y El Fakhri, G Lim, R Bonab, AA Ouyang, JS AF Rakvongthai, Yothin El Fakhri, Georges Lim, Ruth Bonab, Ali A. Ouyang, Jinsong TI Simultaneous Tc-99m-MDP/I-123-MIBG tumor imaging using SPECT-CT: Phantom and constructed patient studies SO MEDICAL PHYSICS LA English DT Article DE simultaneous dual-radionuclide imaging; MDP; MIBG; SPECT-CT; scatter correction ID NEURO-BLASTOMA; BRAIN SPECT; MONTE-CARLO; I-131 MIBG; NEUROBLASTOMA; SCINTIGRAPHY; METAIODOBENZYLGUANIDINE; RECONSTRUCTION; REGISTRATION; DIAGNOSIS AB Purpose: Authors' goal is to evaluate the performance of simultaneous Tc-99m-MDP/I-123-MIBG tumor imaging with fast Monte-Carlo (MC) based joint iterative reconstruction as compared to sequential Tc-99m-MDP and I-123-MIBG tumor imaging. Methods: Noise-free Tc-99m and I-123 SPECT projections were acquired separately using an anthropomorphic torso phantom modified to include a fillable tube around the lungs to mimic ribs. Additionally, Tc-99m and I-123 projections were acquired separately using a 1-cm spherical "tumor" placed at various distances from one detector. Tumor-present data were generated by adding tumor projections to the torso phantom data, which were scaled to the total counts in typical clinical studies. Twenty-five noise realizations were generated by adding Poisson noise to the projection data for each radionuclide. Dual-radionuclide data were synthesized by summing the Tc-99m and I-123 projections. Image reconstruction was performed using: (1) SR-OSEM, ordered subset expectation maximization (OSEM) without scatter correction (SC) using single-radionuclide (SR) data; (2) SR-MC-OSEM, OSEM with a fast MC-based SC using SR data; (3) DR-OSEM, OSEM without SC using dual-radionuclide (DR) data; and (4) DR-MC-JOSEM, joint OSEM with a fast MC-based SC using DR data. Ten Tc-99m-MDP and ten I-123-MIBG data sets, which had tumors mathematically inserted, were also used to evaluate the performance of authors' approach. For the phantom study, relative bias and relative standard deviation of tumor uptake were computed for each tumor using the tumor uptake in the noise-free single-radionuclide images, which were reconstructed by SR-MC-OSEM, as the gold standard. For both the phantom and constructed patient studies, mean contrast and standard deviation of contrast were computed for each tumor for both the single-and dual-radionuclide images. Additionally, contrast recovery was computed as the ratio between mean contrast and the mean contrast for SR-MC-OSEM. Results: For the phantom study, DR-MC-JOSEM yielded 2.7% on average relative bias of tumor uptake using the images, which were reconstructed from the noise-free SR data with SR-MC-OSEM, as the gold-standard. For both the phantom and constructed patient studies, DR-MC-JOSEM yielded 94.7% and 95.2% tumor contrast recovery on average using SR-MC-OSEM as the reference, in the phantom and constructed patient studies, respectively. DR-MC-JOSEM yielded comparable relative standard deviation of bias and standard deviation of contrast to SR-MC-OSEM. Conclusions: Simultaneous Tc-99m-MDP/I-123-MIBG tumor imaging using authors' dual-radionuclide reconstruction approach yielded comparable image quality to sequential Tc-99m-MDP and I-123-MIBG imaging. For patients who need to undergo both scans, authors' approach offers perfectly registered dual-tracer images under identical conditions without compromising image quality, and reduces the imaging cost while increasing patient throughput. (C) 2013 American Association of Physicists in Medicine. C1 [Ouyang, Jinsong] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM ouyang.jinsong@mgh.harvard.edu FU National Institutes of Health (NIH) [R21CA140771, R01HL110241, R21EB012823] FX This work was supported in part by National Institutes of Health (NIH) Grant Nos. R21CA140771, R01HL110241, and R21EB012823. NR 24 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2013 VL 40 IS 10 AR 102506 DI 10.1118/1.4820977 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 231DT UT WOS:000325394400041 PM 24089927 ER PT J AU Rakvongthai, Y Ouyang, JS Guerin, B Li, QZ Alpert, NM El Fakhri, G AF Rakvongthai, Yothin Ouyang, Jinsong Guerin, Bastien Li, Quanzheng Alpert, Nathaniel M. El Fakhri, Georges TI Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach SO MEDICAL PHYSICS LA English DT Article DE direct estimation; preconditioned conjugate gradient; kinetic modeling; parametric imaging; dynamic PET ID POSITRON-EMISSION-TOMOGRAPHY; DYNAMIC PET; EM ALGORITHM; CARDIOLOGY; BINDING; MODELS AB Purpose: Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Methods: Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the preconditioned conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. Results: At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%-29% and 32%-70% for 50 x 106 and 10 x 106 detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 40-50 iterations), while more than 500 iterations were needed for CG. Conclusions: The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method. (C) 2013 American Association of Physicists in Medicine. C1 [El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu FU NIH [NIH-HL110241] FX The authors would like to thank the anonymous reviewers for their constructive comments, which greatly improved the paper. This work was supported in part by NIH (Grant No. NIH-HL110241). NR 30 TC 9 Z9 9 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2013 VL 40 IS 10 AR 102501 DI 10.1118/1.4819821 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 231DT UT WOS:000325394400036 PM 24089922 ER PT J AU Raytchev, M Seco, J AF Raytchev, Milen Seco, Joao TI Proton radiography in three dimensions: A proof of principle of a new technique SO MEDICAL PHYSICS LA English DT Article DE 3D proton radiography; proton radiography; algorithm development; 3D; computed radiography; Monte Carlo ID MULTIPLE-SCATTERING THEORY; COMPUTED-TOMOGRAPHY; MONTE-CARLO; RECONSTRUCTION; BEAM; THERAPY; TOOLKIT; PATIENT AB Purpose: Monte Carlo simulations were used to investigate a range of phantom configurations to establish enabling three-dimensional proton radiographic techniques. Methods: A large parameter space of stacked phantom geometries composed of tissue inhomogeneity materials such as lung, bone, and cartilage inserted within water background were simulated using a purposefully modified version of TOPAS, an application running on top of the GEANT4 Monte Carlo code. The phantoms were grouped in two classes, one with the inhomogeneity inserted only half-way in the lateral direction and another with complete inhomogeneity insertion. The former class was used to calculate the track count and the energy fluence of the protons as they exit the phantoms either having traversed the inhomogeneity or not. The latter class was used to calculate one yield value accounting for loss of protons due to physical processes only and another yield value accounting for deliberately discarded protons due to large scattering angles. A graphical fingerprinting method was developed to determine the inhomogeneity thickness and location within the phantom based on track count and energy fluence information. Two additional yield values extended this method to the general case which also determines the inhomogeneity material and the phantom thickness. Results: The graphical fingerprinting method was manually validated for two, and automatically tested for all, tissue materials using an exhaustive set of inhomogeneity geometries for 16 cm thick phantoms. Unique recognition of test phantom configurations was achieved in the large majority of cases. The method in the general case was further tested using an exhaustive set of inhomogeneity and phantom tissues and geometries where the phantom thicknesses ranged between 8 and 24 cm. Unique recognition of the test phantom configurations was achieved only for part of the phantom parameter space. The correlations between the remaining false positive recognitions were analyzed. Conclusions: The concept of 3D proton radiography for tissue inhomogeneities of simple geometries was established with the current work. In contrast to conventional 2D proton radiography, the main objective of the demonstrated 3D technique is not proton range. Rather, it is to measure the depth and thickness of an inhomogeneity located in an imaged geometry. Further work is needed to extend and apply the method to more complex geometries. (C) 2013 American Association of Physicists in Medicine. C1 [Raytchev, Milen] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Raytchev, M (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM mraytchev@partners.org FU Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center FX The authors thank the TOPAS development team for the provision and support of the alpha version of TOPAS. In particular, the authors are thankful to Jan Schumann for technical help with the source code. The authors also thank the Enterprise Research IS group at Partners Healthcare for the provision and maintenance of the HPC facilities. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. The authors declare no conflict of interest. NR 34 TC 1 Z9 1 U1 0 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2013 VL 40 IS 10 AR 101917 DI 10.1118/1.4822487 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 231DT UT WOS:000325394400033 PM 24089919 ER PT J AU Li, SP Hu, MFG Sun, YQ Yoshioka, N Ibaragi, S Sheng, JH Sun, GJ Kishimoto, K Hu, GF AF Li, Shuping Hu, Miaofen G. Sun, Yeqing Yoshioka, Norie Ibaragi, Soichiro Sheng, Jinghao Sun, Guangjie Kishimoto, Koji Hu, Guo-Fu TI Angiogenin Mediates Androgen-Stimulated Prostate Cancer Growth and Enables Castration Resistance SO MOLECULAR CANCER RESEARCH LA English DT Article ID RIBOSOMAL-RNA TRANSCRIPTION; ENDOTHELIAL-CELLS; INTRAEPITHELIAL NEOPLASIA; NUCLEAR TRANSLOCATION; ATHYMIC MICE; RECEPTOR; PROLIFERATION; PROGRESSION; EXPRESSION; CARCINOMA AB The androgen receptor (AR) is a critical effector of prostate cancer development and progression. Androgen-dependent prostate cancer is reliant on the function of AR for growth and progression. Most castration-resistant prostate cancer (CRPC) remains dependent on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of prostate cancer cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the mechanism by which AR regulates rRNA transcription is unknown. Here, investigation revealed that angiogenin (ANG), a member of the secreted ribonuclease superfamily, is upregulated in prostate cancer and mediates androgen-stimulated rRNA transcription in prostate cancer cells. Upon androgen stimulation, ANG undergoes nuclear translocation in androgen-dependent prostate cancer cells, where it binds to the rDNA promoter and stimulates rRNA transcription. ANG antagonists inhibit androgen-induced rRNA transcription and cell proliferation in androgen-dependent prostate cancer cells. Interestingly, ANG also mediates androgen-independent rRNA transcription through a mechanism that involves its constitutive nuclear translocation in androgen-insensitive prostate cancer cells, resulting in a constant rRNA overproduction and thereby stimulating cell proliferation. Critically, ANG overexpression in androgen-dependent prostate cancer cells enables castration-resistant growth of otherwise androgen-dependent cells. Thus, ANG-stimulated rRNA transcription is not only an essential component for androgen-dependent growth of prostate cancer but also contributes to the transition of prostate cancer from androgen-dependent to castration-resistant growth status. Implications: The ability of angiogenin to regulate rRNA transcription and prostate cancer growth makes it a viable target for therapy. C1 [Li, Shuping; Hu, Miaofen G.; Sheng, Jinghao; Hu, Guo-Fu] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Sun, Guangjie] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Sun, Yeqing] Dalian Maritime Univ, Inst Environm Syst Biol, Dalian, Peoples R China. [Yoshioka, Norie; Ibaragi, Soichiro; Kishimoto, Koji] Okayama Univ, Dept Oral & Maxillofacial Surg, Okayama 7008530, Japan. RP Hu, GF (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, 800 Washington St, Boston, MA 02111 USA. EM ghu@tuftsmedicalcenter.org FU NIH [R01 CA105241] FX This work was support by NIH grant R01 CA105241. NR 45 TC 9 Z9 13 U1 2 U2 8 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 OCT PY 2013 VL 11 IS 10 BP 1203 EP 1214 DI 10.1158/1541-7786.MCR-13-0072 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 236NR UT WOS:000325805000008 PM 23851444 ER PT J AU Zangi, L Lui, KO von Gise, A Ma, Q Ebina, W Ptaszek, LM Spater, D Xu, HS Tabebordbar, M Gorbatov, R Sena, B Nahrendorf, M Briscoe, DM Li, RA Wagers, AJ Rossi, DJ Pu, WT Chien, KR AF Zangi, Lior Lui, Kathy O. von Gise, Alexander Ma, Qing Ebina, Wataru Ptaszek, Leon M. Spater, Daniela Xu, Huansheng Tabebordbar, Mohammadsharif Gorbatov, Rostic Sena, Brena Nahrendorf, Matthias Briscoe, David M. Li, Ronald A. Wagers, Amy J. Rossi, Derrick J. Pu, William T. Chien, Kenneth R. TI Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction SO NATURE BIOTECHNOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ADENOASSOCIATED VIRUS VECTORS; ADULT NEOVASCULARIZATION; EPICARDIAL PROGENITORS; HIGHLY EFFICIENT; SKELETAL-MUSCLE; GENE DELIVERY; SMOOTH-MUSCLE; CYTOSOLIC DNA; BETA-CATENIN AB In a cell-free approach to regenerative therapeutics, transient application of paracrine factors in vivo could be used to alter the behavior and fate of progenitor cells to achieve sustained clinical benefits. Here we show that intramyocardial injection of synthetic modified RNA (modRNA) encoding human vascular endothelial growth factor-A (VEGF-A) results in the expansion and directed differentiation of endogenous heart progenitors in a mouse myocardial infarction model. VEGF-A modRNA markedly improved heart function and enhanced long-term survival of recipients. This improvement was in part due to mobilization of epicardial progenitor cells and redirection of their differentiation toward cardiovascular cell types. Direct in vivo comparison with DNA vectors and temporal control with VEGF inhibitors revealed the greatly increased efficacy of pulse-like delivery of VEGF-A. Our results suggest that modRNA is a versatile approach for expressing paracrine factors as cell fate switches to control progenitor cell fate and thereby enhance long-term organ repair. C1 [Zangi, Lior; Lui, Kathy O.; Ebina, Wataru; Ptaszek, Leon M.; Spater, Daniela; Xu, Huansheng; Tabebordbar, Mohammadsharif; Wagers, Amy J.; Rossi, Derrick J.; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Zangi, Lior; Lui, Kathy O.; Ptaszek, Leon M.; Spater, Daniela; Xu, Huansheng; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Zangi, Lior; von Gise, Alexander; Ma, Qing; Pu, William T.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Zangi, Lior; Ebina, Wataru; Rossi, Derrick J.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Zangi, Lior; Ebina, Wataru; Rossi, Derrick J.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Zangi, Lior; von Gise, Alexander; Ma, Qing; Pu, William T.] Boston & Harvard Stem Cell Inst, Cambridge, MA USA. [Zangi, Lior; von Gise, Alexander; Ma, Qing; Pu, William T.] Univ Hong Kong, LKS Fac Med, Pokfulam, Hong Kong, Peoples R China. [Lui, Kathy O.; Xu, Huansheng; Li, Ronald A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ptaszek, Leon M.] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Tabebordbar, Mohammadsharif] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Gorbatov, Rostic; Sena, Brena; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Briscoe, David M.] Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. [Li, Ronald A.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY USA. [Wagers, Amy J.] Howard Hughes Med Inst, Cambridge, MA USA. [Chien, Kenneth R.] Karolinska Inst, Dept Cell & Mol Biol & Med, Stockholm, Sweden. RP Chien, KR (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM wpu@enders.tch.harvard.edu; kenneth.chien@ki.se RI Lui, Kathy O./E-4883-2015 OI Lui, Kathy O./0000-0002-1616-3643 FU US National Institutes of Health [U01H100408, U01HL098166, U01JL100401, R01HL094683, RC1HL099618, UO1HL100402] FX This work was funded by US National Institutes of Health U01H100408 (K.R.C.), U01HL098166 (K.R.C.), U01JL100401 (W.T.P.), R01HL094683 (W.T.P.), RC1HL099618 (K.R.C., W.T.P.) and UO1HL100402 (A.J.W.). K.O.L. held a Croucher Foundation Fellowship and A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. We thank R. Liao, J. Guan, J. Truelove, L. Bu, M. Stachel, K. Buac, V. Priestly, R. Gazit, K. Ketman, N. Barteneva, A. He, S. Stevens, B. Zhou and L. Warren for all their help in this project. Adult cardiomyocytes were a kind gift from R. Liao (Biological and Biomaterial Science, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School). NR 55 TC 131 Z9 135 U1 10 U2 51 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2013 VL 31 IS 10 BP 898 EP + DI 10.1038/nbt.2682 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 233CA UT WOS:000325541300018 PM 24013197 ER PT J AU Kreydin, EI Eisner, BH AF Kreydin, Evgeniy I. Eisner, Brian H. TI Risk factors for sepsis after percutaneous renal stone surgery SO NATURE REVIEWS UROLOGY LA English DT Review ID INFLAMMATORY RESPONSE SYNDROME; URINARY-TRACT INFECTION; ANTIMICROBIAL PROPHYLAXIS; ANTIBIOTIC-PROPHYLAXIS; POSTOPERATIVE FEVER; UROLOGIC SURGERY; PURULENT FLUID; PELVIC URINE; SEPTIC SHOCK; NEPHROLITHOTOMY AB Since its introduction into the endourologist's armamentarium almost 40 years ago, percutaneous nephrolithotomy (PCNL) has become the standard of care for patients with large-volume nephrolithiasis. Postoperative infection is one of the most common complications of the procedure, and postoperative sepsis is one of the most detrimental. A number of factors have been found to increase the risk of postoperative sepsis. These include patient characteristics that are known preoperatively, such as urine culture obtained from the bladder or from the renal pelvis if percutaneous access to the renal pelvis is obtained in advance to the procedure. Neurogenic bladder dysfunction secondary to spinal cord injury and anatomical renal abnormalities, such as pelvicalyceal dilatation, have also been associated with increased incidence of fever and sepsis after the procedure. Several intraoperative factors, such as the average renal pressure sustained during PCNL and the operative time, also seem to increase the risk of sepsis. Finally, the contribution of postoperative factors, such as presence of a nephrostomy tube or a urethral catheter, has also been investigated. A short preoperative course of antibiotics has been found to significantly decrease the rate of postoperative fever and sepsis. Novel agents targeted at sepsis prevention and treatment, such as anti-endotoxin antibodies and cholesterol-lowering drugs statins, are currently under investigation. C1 [Kreydin, Evgeniy I.; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 61 TC 26 Z9 29 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 EI 1759-4820 J9 NAT REV UROL JI Nat. Rev. Urol. PD OCT PY 2013 VL 10 IS 10 BP 598 EP 605 DI 10.1038/nrurol.2013.183 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 233FH UT WOS:000325551700008 PM 23999583 ER PT J AU Toms, AV Deshpande, A McNally, R Jeong, Y Rogers, JM Kim, CU Gruner, SM Ficarro, SB Marto, JA Sattler, M Griffin, JD Eck, MJ AF Toms, Angela V. Deshpande, Anagha McNally, Randall Jeong, Youngjee Rogers, Julia M. Kim, Chae Un Gruner, Sol M. Ficarro, Scott B. Marto, Jarrod A. Sattler, Martin Griffin, James D. Eck, Michael J. TI Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYCYTHEMIA-VERA; TYROSINE KINASE; PROTEIN-KINASE; MYELOPROLIFERATIVE DISORDERS; JANUS KINASES; MUTATIONS; INHIBITORS; JAK2V617F; RECEPTOR AB The V617F mutation in the Jak2 pseudokinase domain causes myeloproliferative neoplasms, and the equivalent mutation in Jak1 (V658F) is found in T-cell leukemias. Crystal structures of wild-type and V658F-mutant human Jak1 pseudokinase reveal a conformational switch that remodels a linker segment encoded by exon 12, which is also a site of mutations in Jak2. This switch is required for V617F-mediated Jak2 activation and possibly for physiologic Jak activation. C1 [Toms, Angela V.; McNally, Randall; Jeong, Youngjee; Ficarro, Scott B.; Marto, Jarrod A.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Toms, Angela V.; McNally, Randall; Rogers, Julia M.; Ficarro, Scott B.; Marto, Jarrod A.; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Deshpande, Anagha; Sattler, Martin; Griffin, James D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Deshpande, Anagha; Sattler, Martin; Griffin, James D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rogers, Julia M.] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA. [Kim, Chae Un; Gruner, Sol M.] Cornell Univ, Cornell High Energy Synchrotron Source, Ithaca, NY 14853 USA. [Gruner, Sol M.] Cornell Univ, Dept Phys, Ithaca, NY 14853 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu RI Gruner, Sol/G-2924-2010; Kim, Chae Un/D-2956-2014 OI Gruner, Sol/0000-0002-1171-4426; FU US National Institutes of Health (NIH); NIH [CA134660, GM008313, CA936132]; Novartis Institutes for Biomedical Research FX We thank beamline personnel at the Macromolecular Crystallography Resource at the Cornell High Energy Synchrotron Source (MacCHESS) and the Northeast Collaborative Access Team at the Advanced Photon Source, Argonne National Laboratory (NE-CAT) for assistance with data collection and processing. We thank K. Arnett for generous help with Jak1 autophosphorylation experiments. MacCHESS and NE-CAT are supported by grants from the US National Institutes of Health (NIH). This work was supported in part by NIH grant CA134660 (M. S.) and NIH training grants GM008313 (J.M.R.) and CA936132 (R. M.), and by funding from Novartis Institutes for Biomedical Research (M.J.E.). NR 31 TC 21 Z9 21 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2013 VL 20 IS 10 BP 1221 EP + DI 10.1038/nsmb.2673 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 230UV UT WOS:000325369500014 PM 24013208 ER PT J AU Liu, CY Iglesias, JE Tu, ZW AF Liu, Cheng-Yi Iglesias, Juan Eugenio Tu, Zhuowen CA Alzheimer's Dis Neuroimaging Initi TI Deformable Templates Guided Discriminative Models for Robust 3D Brain MRI Segmentation SO NEUROINFORMATICS LA English DT Article DE Brain image segmentation; Fusion; Deformable templates; Discriminative models; Generative models ID MAGNETIC-RESONANCE IMAGES; SPATIAL DECISION FORESTS; SUPPORT VECTOR MACHINES; MS LESION SEGMENTATION; MARKOV DEPENDENCE TREE; TISSUE CLASSIFICATION; TUMOR SEGMENTATION; INTENSITY NONUNIFORMITY; PATTERN-CLASSIFICATION; AUTOMATED SEGMENTATION AB Automatically segmenting anatomical structures from 3D brain MRI images is an important task in neuroimaging. One major challenge is to design and learn effective image models accounting for the large variability in anatomy and data acquisition protocols. A deformable template is a type of generative model that attempts to explicitly match an input image with a template (atlas), and thus, they are robust against global intensity changes. On the other hand, discriminative models combine local image features to capture complex image patterns. In this paper, we propose a robust brain image segmentation algorithm that fuses together deformable templates and informative features. It takes advantage of the adaptation capability of the generative model and the classification power of the discriminative models. The proposed algorithm achieves both robustness and efficiency, and can be used to segment brain MRI images with large anatomical variations. We perform an extensive experimental study on four datasets of T1-weighted brain MRI data from different sources (1,082 MRI scans in total) and observe consistent improvement over the state-of-the-art systems. C1 [Liu, Cheng-Yi; Tu, Zhuowen] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Iglesias, Juan Eugenio] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Liu, CY (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, 635 Charles E Young Dr South,Suite 225, Los Angeles, CA 90095 USA. EM chengyiliu@gmail.com; j.e.iglesias@gmail.com; zhuowen.tu@gmail.com RI Saykin, Andrew/A-1318-2007; Kowall, Neil/G-6364-2012; Iglesias, Juan Eugenio/K-1184-2014; OI Saykin, Andrew/0000-0002-1376-8532; Kowall, Neil/0000-0002-6624-0213; Iglesias, Juan Eugenio/0000-0001-7569-173X; Preda, Adrian /0000-0003-3373-2438 FU NSF [IIS-0844566, IIS-1216528]; ONR [N000140910099] FX This work was funded by NSF CAREER award IIS-0844566, ONR award no. N000140910099, and NSF award IIS-1216528. NR 91 TC 4 Z9 5 U1 0 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 EI 1559-0089 J9 NEUROINFORMATICS JI Neuroinformatics PD OCT PY 2013 VL 11 IS 4 BP 447 EP 468 DI 10.1007/s12021-013-9190-5 PG 22 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 236AY UT WOS:000325767100005 PM 23836390 ER PT J AU Charalambous, CC Bonilha, HS Kautz, SA Gregory, CM Bowden, MG AF Charalambous, Charalambos C. Bonilha, Heather Shaw Kautz, Steven A. Gregory, Chris M. Bowden, Mark G. TI Rehabilitating Walking Speed Poststroke With Treadmill-Based Interventions: A Systematic Review of Randomized Controlled Trials SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE cerebrovascular accident; walking; activity-based interventions; rehabilitation ID BODY-WEIGHT SUPPORT; SPINAL-CORD-INJURY; OVERGROUND WALKING; IMPROVES WALKING; STROKE REHABILITATION; ASSISTED WALKING; EXERCISE; OUTCOMES; AMBULATION; SURVIVORS AB Background. In the past several years, several randomized controlled trials (RCTs) have been reported regarding the efficacy of treadmill-based walking-specific rehabilitation programs, either individually (TT) or combined with body weight support (BWSTT), over control group therapies poststroke. No clear consensus exists as to whether treadmill-based interventions are superior in rehabilitating walking speed (WS) poststroke. Objective. To review published RCTs examining TT and BWSTT poststroke and describe the effects on improving and retaining WS. Methods. A systematic literature search in computerized databases was conducted to identify RCTs whose methodological quality was assessed with PEDro. Pre- and post-WS, change in WS, functional outcomes, and follow-up speed were extracted and calculated from each study. Additionally, statistical results of each study were examined, and the intragroup and intergroup effect sizes (ESintra and ESinter, respectively) were calculated. Results. All studies (8 TT; 7 BWSTT) met the inclusion criteria, and their methodological quality was generally good, with a mean PEDro score 6.9/10. Of the 15 studies, 8 studies (4 TT; 4 BWSTT) reported intragroup significant increases of WS, whereas only 4 (4 TT) found superiority of treadmill interventions. Nine studies demonstrated large ESintra (4 TT; 5 BWSTT), yet only 3 showed large ESinter (1 TT; 2 BWSTT). Four studies (2 TT and 2 BWSTT) reported retention of gains in WS, regardless of intervention. Conclusions. Treadmill-based interventions poststroke may increase and retain WS, but their universal superiority to other control group therapies has failed to be established. C1 [Charalambous, Charalambos C.; Bonilha, Heather Shaw; Kautz, Steven A.; Gregory, Chris M.; Bowden, Mark G.] Med Univ S Carolina, Charleston, SC 29425 USA. [Kautz, Steven A.; Gregory, Chris M.; Bowden, Mark G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bowden, MG (reprint author), 77 President St,MSC 700, Charleston, SC 29425 USA. EM bowdenm@musc.edu OI Kautz, Steven/0000-0003-3151-8235 FU NIH [KL2 RR029880, KL2 TR000060]; VA RRD [A6776S, B7177M] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This material is the result of work supported with resources and the use of facilities at the Ralph H. Johnson VA Medical Center in Charleston, SC. This work was supported by NIH Grant Numbers KL2 RR029880 and KL2 TR000060 (HSB), VA RR&D A6776S (SAK), and VA RR&D B7177M (MGB). NR 31 TC 2 Z9 2 U1 0 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD OCT PY 2013 VL 27 IS 8 BP 709 EP 721 DI 10.1177/1545968313491005 PG 13 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 220NQ UT WOS:000324591700005 PM 23764885 ER PT J AU Dobscha, SK AF Dobscha, Steven K. TI Prescription Opioids and Benzodiazepines: Moving Beyond "Just Say No" SO PAIN MEDICINE LA English DT Editorial Material ID PERSISTENT PAIN; THERAPY C1 Portland VA Med Ctr, Ctr Improve Vet Involvement Care CIVIC, Portland, OR USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Ctr Improve Vet Involvement Care CIVIC, Portland, OR USA. NR 16 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD OCT PY 2013 VL 14 IS 10 BP 1447 EP 1449 DI 10.1111/pme.12237 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 235BX UT WOS:000325691000003 PM 24588852 ER PT J AU Stephens, C Sackett, N Pierce, R Schopfer, D Schmajuk, G Moy, N Bachhuber, M Wallhagen, MI Lee, SJ AF Stephens, Caroline Sackett, Nathan Pierce, Read Schopfer, David Schmajuk, Gabriela Moy, Nicholas Bachhuber, Melissa Wallhagen, Margaret I. Lee, Sei J. TI Transitional Care Challenges of Rehospitalized Veterans: Listening to Patients and Providers SO POPULATION HEALTH MANAGEMENT LA English DT Article ID HEALTH-CARE; HOSPITAL DISCHARGE; HOMELESS PERSONS; CONTROLLED-TRIAL; PROGRAM; ELDERS AB Readmissions to the hospital are common and costly, often resulting from poor care coordination. Despite increased attention given to improving the quality and safety of care transitions, little is known about patient and provider perspectives of the transitional care needs of rehospitalized Veterans. As part of a larger quality improvement initiative to reduce hospital readmissions, the authors conducted semi-structured interviews with 25 patients and 14 of their interdisciplinary health care providers to better understand their perspectives of the transitional care needs and challenges faced by rehospitalized Veterans. Patients identified 3 common themes that led to rehospitalization: (1) knowledge gaps and deferred power; (2) difficulties navigating the health care system; and (3) complex psychiatric and social needs. Providers identified different themes that led to rehospitalization: (1) substance abuse and mental illness; (2) lack of social or financial support and homelessness; (3) premature discharge and poor communication; and (4) nonadherence with follow-up. Results underscore that rehospitalized Veterans have a complex overlapping profile of real and perceived physical, mental, and social needs. A paradigm of disempowerment and deferred responsibility appears to exist between patients and providers that contributes to ineffective care transitions, resulting in readmissions. These results highlight the cultural constraints on systems of care and suggest that process improvements should focus on increasing the sense of partnership between patients and providers, while simultaneously creating a culture of empowerment, ownership, and engagement, to achieve success in reducing hospital readmissions. (Population Health Management 2013;16:326-331) C1 [Stephens, Caroline; Sackett, Nathan; Moy, Nicholas; Lee, Sei J.] San Francisco VA Med Ctr, Div Geriatr Palliat & Extended Care, San Francisco, CA 94121 USA. [Pierce, Read; Bachhuber, Melissa] San Francisco VA Med Ctr, Dept Hosp Med, San Francisco, CA 94121 USA. [Schopfer, David] San Francisco VA Med Ctr, Dept Cardiol, San Francisco, CA 94121 USA. [Schmajuk, Gabriela] San Francisco VA Med Ctr, Dept Rheumatol, San Francisco, CA 94121 USA. [Stephens, Caroline; Schopfer, David; Schmajuk, Gabriela; Moy, Nicholas; Wallhagen, Margaret I.; Lee, Sei J.] San Francisco VA Med Ctr, Dept VA Qual Scholar, San Francisco, CA 94121 USA. [Stephens, Caroline] Univ Calif San Francisco, San Francisco Sch Nursing, Dept Community Hlth Syst & Social & Behav Sci, San Francisco, CA 94143 USA. [Wallhagen, Margaret I.] Univ Calif San Francisco, San Francisco Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Stephens, Caroline] John A Hartford Fdn, San Francisco, CA USA. [Sackett, Nathan] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Sackett, Nathan] Univ Calif San Francisco, Joint Med Program, San Francisco, CA 94143 USA. [Pierce, Read; Bachhuber, Melissa] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] Univ Calif San Francisco, Div Rheumatol, San Francisco, CA 94143 USA. [Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Stephens, C (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM caroline.stephens@ucsf.edu FU Gordon & Betty Moore Foundation; California Health Care Foundation FX The authors received the following financial support for the research, authorship, and/or publication of this article: The Gordon & Betty Moore Foundation and the California Health Care Foundation provided funding for this project; the VA Quality Scholars program provided postdoctoral training support for Drs. Stephens, Schopfer, Schmajuk, and Moy; the John A. Hartford Foundation/Atlantic Philanthropies Claire M. Fagin Fellows program provided postdoctoral training support for Dr Stephens. NR 32 TC 4 Z9 5 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1942-7891 EI 1942-7905 J9 POPUL HEALTH MANAG JI Popul. Health Manag. PD OCT 1 PY 2013 VL 16 IS 5 BP 326 EP 331 DI 10.1089/pop.2012.0104 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 216SU UT WOS:000324305200008 PM 23560514 ER PT J AU Condon, P Desbordes, G Miller, WB DeSteno, D AF Condon, Paul Desbordes, Gaelle Miller, Willa B. DeSteno, David TI Meditation Increases Compassionate Responses to Suffering SO PSYCHOLOGICAL SCIENCE LA English DT Article C1 [Condon, Paul; DeSteno, David] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Desbordes, Gaelle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Miller, Willa B.] Harvard Univ, Dept Relig, Cambridge, MA 02138 USA. RP Condon, P (reprint author), Northeastern Univ, Dept Psychol, 360 Huntington Ave, Boston, MA 02115 USA. EM p.condon@neu.edu; d.desteno@gmail.com RI Desbordes, Gaelle/B-5924-2008 OI Desbordes, Gaelle/0000-0002-6117-2880 NR 8 TC 44 Z9 45 U1 6 U2 25 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 OCT PY 2013 VL 24 IS 10 BP 2125 EP 2127 DI 10.1177/0956797613485603 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 233GC UT WOS:000325554800029 PM 23965376 ER PT J AU Gradus, JL Street, AE Suvak, MK Resick, PA AF Gradus, Jaimie L. Street, Amy E. Suvak, Michael K. Resick, Patricia A. TI Predictors of Suicidal Ideation in a Gender-Stratified Sample of OEF/OIF Veterans SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID MILITARY PERSONNEL; RISK-FACTORS; BEHAVIOR; HEALTH; WOMEN; VICTIMIZATION; DEPRESSION; ADULTS AB There is a growing concern about suicide among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans. We examined the role of postdeployment mental health in associations between deployment stressors and postdeployment suicidal ideation (SI) in a national sample of 2,321 female and male OEF/OIF veterans. Data were obtained via survey, and path analysis was used. For women and men, mental health symptoms largely accounted for associations between deployment stressors and SI; however, they only partly accounted for the sexual harassment and SI association among women. These findings enhance the understanding of the mental health profile of OEF/OIF veterans. C1 [Gradus, Jaimie L.; Street, Amy E.; Suvak, Michael K.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Gradus, Jaimie L.; Street, Amy E.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM Jaimie.Gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 42 TC 17 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD OCT PY 2013 VL 43 IS 5 BP 574 EP 588 DI 10.1111/sltb.12040 PG 15 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 233CR UT WOS:000325543400010 PM 23829657 ER PT J AU Berry, DL Halpenny, B Hong, FX Wolpin, S Lober, WB Russell, KJ Ellis, WJ Govindarajulu, U Bosco, J Davison, BJ Bennett, G Terris, MK Barsevick, A Lin, DW Yang, CC Swanson, G AF Berry, Donna L. Halpenny, Barbara Hong, Fangxin Wolpin, Seth Lober, William B. Russell, Kenneth J. Ellis, William J. Govindarajulu, Usha Bosco, Jaclyn Davison, B. Joyce Bennett, Gerald Terris, Martha K. Barsevick, Andrea Lin, Daniel W. Yang, Claire C. Swanson, Greg TI The Personal Patient Profile-Prostate decision support for men with localized prostate cancer: A multi-center randomized trial SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Randomized trial; Internet; Decision making; Decisional conflict ID AID; INTERVENTION; EDUCATION; CHOICE; RISK; COMMUNICATION; DISPARITIES; VALIDATION; DILEMMA; SYSTEM AB Objective: The purpose of this trial was to compare usual patient education plus the Internet-based Personal Patient Profile-Prostate, vs. usual education alone, on conflict associated with decision making, plus explore time-to-treatment, and treatment choice. Methods: A randomized, multi-center clinical trial was conducted with measures at baseline, 1-, and 6 months. Men with newly diagnosed localized prostate cancer (CaP) who sought consultation at urology, radiation oncology, or multi-disciplinary clinics in 4 geographically-distinct American cities were recruited. Intervention group participants used the Personal Patient Profile-Prostate, a decision support system comprised of customized text and video coaching regarding potential outcomes, influential factors, and communication with care providers. The primary outcome, patient-reported decisional conflict, was evaluated over time using generalized estimating equations to fit generalized linear models. Additional outcomes, time-to-treatment, treatment choice, and program acceptability/usefulness, were explored. Results: A total of 494 eligible men were randomized (266 intervention; 228 control). The intervention reduced adjusted decisional conflict over time compared with the control group, for the uncertainty score (estimate -3.61; (confidence interval, -7.01, 0.22), and values clarity (estimate -3.57; confidence interval (-5.85,-1.30). Borderline effect was seen for the total decisional conflict score (estimate -1.75; confidence interval (-3.61,0.11). Time-to-treatment was comparable between groups, while undecided men in the intervention group chose brachytherapy more often than in the control group. Acceptability and usefulness were highly rated. Conclusion: The Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized CaP. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a CaP treatment that is consistent with the patient values and preferences. (C) 2013 Elsevier Inc. All rights reserved. C1 [Berry, Donna L.; Halpenny, Barbara; Hong, Fangxin; Bosco, Jaclyn] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02215 USA. [Hong, Fangxin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Wolpin, Seth; Lober, William B.] Univ Washington, Seattle, WA 98195 USA. [Russell, Kenneth J.] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Ellis, William J.; Lin, Daniel W.; Yang, Claire C.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Govindarajulu, Usha] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Davison, B. Joyce] Univ Saskatchewan, Saskatoon, SK, Canada. [Bennett, Gerald] Georgia Hlth Sci Univ, Coll Nursing, Charlie Norwood VA Med Ctr, Augusta, GA 30904 USA. [Terris, Martha K.] Charlie Norwood VA Med Ctr, Div Surg, Urol Sect, Augusta, GA 30904 USA. [Terris, Martha K.] Georgia Hlth Sci Univ, Dept Surg, Urol Sect, Augusta, GA 30904 USA. [Barsevick, Andrea] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Lin, Daniel W.] VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. [Swanson, Greg] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Radiat Oncol, San Antonio, TX 78229 USA. RP Swanson, G (reprint author), Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Radiat Oncol, San Antonio, TX 78229 USA. EM donna_berry@dfci.harvard.edu OI Terris, Martha/0000-0002-3843-7270; Barsevick, Andrea/0000-0003-1829-6826 FU NIH [R01-NR009692] FX NIH, R01-NR009692. The funder did not have a role in the manuscript. This material is the result of work supported with resources and use of facilities at the Charlie Norwood VA Medical Center, Augusta, GA, VA Puget Sound Healthcare System, Seattle, WA, and the South Texas Veterans Health Care System, San Antonio, TX, all of which approved the submission of the manuscript. D.L.B, B.H., and F.H. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 56 TC 23 Z9 23 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD OCT PY 2013 VL 31 IS 7 BP 1012 EP 1021 DI 10.1016/j.urolonc.2011.10.004 PG 10 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 234SJ UT WOS:000325664300011 PM 22153756 ER PT J AU Gershman, B Dahl, DM Olumi, AF Young, RH McDougal, WS Wu, CL AF Gershman, Boris Dahl, Douglas M. Olumi, Aria F. Young, Robert H. McDougal, W. Scott Wu, Chin-Lee TI Smaller prostate gland size and older age predict Gleason score upgrading SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Gleason score; Upgrading; Size; Age ID RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; SEARCH DATABASE; NEEDLE BIOPSIES; CLINICAL STAGE; HIGH-GRADE; CANCER; VOLUME; MEN; ASSOCIATION AB Objectives: Gleason score is important for prostate cancer (CaP) risk stratification and prognostication but has a significant rate of upgrading. We examined the effect of prostate size and age on upgrading of Gleason 6 CaP. Materials and methods: A retrospective review was performed of patients with Gleason 6 CaP who underwent radical prostatectomy from 2001 through 2010. Preoperative clinical and pathologic variables were assessed to determine association with risk of upgrading at prostatectomy. Results: A total of 1,836 patients were identified with Gleason 6 on prostate biopsy. Upgrading was observed in 543 (29.6%) patients with a final Gleason score of 3+4 in 463 (25.2%), 4+3 in 49 (2.7%), and 8-10 in 31 (1.7%). On univariate logistic regression, age, prostate weight, and PSA were significant predictors of Gleason score upgrading and remained significant on multiple logistic regression. Prostate weight was inversely related to risk of upgrading. To further explore this effect, we performed multiple logistic regression to examine risk of Gleason 6, 7, or 8-10 disease in 2,493 patients with Gleason 6-10 at prostatectomy. After controlling for age and PSA, there was a progressively increased risk of Gleason 6, 7, and 8-10 disease with decreasing prostate weight. Conclusions: Older age, higher PSA, and smaller prostate gland size are associated with increased risk of Gleason score upgrading. The inverse relationship of prostate weight to risk of Gleason upgrading may be related to increased high-grade disease in smaller glands. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gershman, Boris; Dahl, Douglas M.; Olumi, Aria F.; McDougal, W. Scott; Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Young, Robert H.; Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Wu, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. EM cwu2@partners.org NR 31 TC 7 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD OCT PY 2013 VL 31 IS 7 BP 1033 EP 1037 DI 10.1016/j.urolonc.2011.11.032 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 234SJ UT WOS:000325664300013 PM 22206627 ER PT J AU Gershman, B Zietman, AL Feldman, AS McDougal, WS AF Gershman, Boris Zietman, Anthony L. Feldman, Adam S. McDougal, W. Scott TI Transperineal template-guided prostate biopsy for patients with persistently elevated PSA and multiple prior negative biopsies SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Biopsy; PSA; Prostate cancer; Transperineal; Template ID TRANSITION ZONE BIOPSIES; CANCER-DETECTION; DIAGNOSTIC EFFICACY; SATURATION BIOPSY; CORE DISTRIBUTION; MEN AB Objective: To evaluate the use of transperineal template-guided prostate biopsy for patients with persistently elevated PSA despite multiple negative prior biopsies. Materials and methods: A retrospective review was performed of patients with at least two prior prostate biopsies who underwent transperineal template-guided biopsy. Electronic medical records were reviewed to obtain relevant clinical, laboratory, and pathologic data. Results: A total of 34 patients underwent transperineal template-guided biopsy. Patients had a mean of 3.7 +/- 1.6 (range 2-8) prior biopsies, including prior negative transurethral resection (TUR) biopsy in 6 (17.6%) patients. Prostate cancer was detected in 17 (50%) of the 34 patients. Of these, 14 (82.4%) patients had cancer in the anterior prostate, 9 (52.9%) patients had cancer in the apical prostate, and 16 (94.1%) patients had cancer in either the anterior or apical prostate. Gleason score was 3+3 in 9 (52.9%) patients and 3+4 or greater in 7 (47.1%) patients. The Diem number of positive cores was 4.5 +/- 3.0 (range 1-11). Of the 17 patients with a diagnosis of cancer, 7 underwent radical prostatectomy, 7 underwent radiation therapy, 1 elected active surveillance, and 1 was deciding between surgery and radiation therapy; 1 patient received palliative chemotherapy for synchronous metastatic pancreatic carcinoma. Patients in whom cancer was detected had significantly smaller prostate volume, higher PSA, higher PSA density, and greater PSA velocity. Conclusions: Transperineal template-guided prostate biopsy is an effective technique for detecting cancer in patients with persistently elevated PSA despite multiple negative biopsies. It improves sampling of the anterior and apical prostate, and should be included as part of the diagnostic algorithm to reduce extensive repeat biopsy. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gershman, Boris; Feldman, Adam S.; McDougal, W. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Gershman, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 28 TC 15 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD OCT PY 2013 VL 31 IS 7 BP 1093 EP 1097 DI 10.1016/j.urolonc.2012.01.001 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 234SJ UT WOS:000325664300022 PM 22305626 ER PT J AU Mousa, AY Alhalbouni, S Abu-Halimah, S Gill, G Sadek, B Nanjundappa, A Hass, SM AbuRahma, AF AF Mousa, Albeir Y. Alhalbouni, Saadi Abu-Halimah, Shadi Gill, Gurpreet Sadek, Betro Nanjundappa, Aravinda Hass, Stephen M. AbuRahma, Ali F. TI Cystic Adventitial Disease of the Common Femoral Vein: A Case Report and Review of the Literature SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE cystic; venous; adventitial; mucinous; femoral ID POPLITEAL ARTERY; THROMBOSIS; RESOLUTION AB We report on a 52-year-old female patient who presented with a 6-month history of right lower extremity swelling and tenderness. The patient was treated as an outpatient with full anticoagulation, without any improvement. Her medical history was significant for hypertension and high cholesterol, and she had a full coagulopathy profile that was negative for any hypercoagulable syndrome. On examination, the patient was moderately obese, with significant tenderness over the medial aspect of the right groin. A venous duplex examination revealed hypoechoic structure +/- acute deep vein thrombosis of right common femoral vein (CFV). A computed tomography of the venous phase revealed an eccentric compression over the medial wall of the right CFV. During surgical exploration, adventitial cystic mucinous disease was enucleated from the medial wall of the right CFV, and the pathological examination confirmed the diagnosis. The postoperative course was uneventful, and all swelling and tenderness were completely resolved. The patient continued to do well, and she had an unremarkable venous duplex evaluation at her 6-month follow-up. C1 [Mousa, Albeir Y.; Alhalbouni, Saadi; Abu-Halimah, Shadi; Gill, Gurpreet; Nanjundappa, Aravinda; Hass, Stephen M.; AbuRahma, Ali F.] W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Dept Surg, Charleston, WV 25304 USA. [Mousa, Albeir Y.; Alhalbouni, Saadi; Abu-Halimah, Shadi; Gill, Gurpreet; Nanjundappa, Aravinda; Hass, Stephen M.; AbuRahma, Ali F.] Charleston Area Med Ctr, Dept Surg, Charleston, WV 25304 USA. [Sadek, Betro] Harvard Univ, Massachusetts Gen Hosp, Med Sch Boston, Cambridge, MA 02138 USA. RP Mousa, AY (reprint author), W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Dept Surg, 3110 MacCorkle Ave SE, Charleston, WV 25304 USA. EM amousa@hsc.wvu.edu RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 25 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 EI 1938-9116 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD OCT PY 2013 VL 47 IS 7 BP 569 EP 572 DI 10.1177/1538574413497110 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 220NN UT WOS:000324591400015 PM 23873672 ER PT J AU Liew, G Ali, N Do, S Petranovic, M Cury, R Brady, T Hoffmann, U Ghoshhajra, B AF Liew, Gary Ali, Nabeel Do, Synho Petranovic, Milena Cury, Ricardo Brady, Thomas Hoffmann, Udo Ghoshhajra, Brian TI A Novel Analysis Algorithm for Potential Quantitative Assessment of Myocardial Computed Tomography Perfusion SO ACADEMIC RADIOLOGY LA English DT Article DE Computed tomography; image analysis; cardiac imaging; algorithm; myocardial perfusion ID ISCHEMIA AB Rationale and Objectives: Cardiac computed tomography (CT) has emerged as a robust modality for imaging coronary stenosis and has recently been used to evaluate myocardial abnormalities such as ischemic perfusion defects and infarction. We developed a new image analysis-algorithm for the semiautomatic and quantitative assessment of myocardial perfusion by CT. Materials and Methods: The algorithm semiautomatically segments two-dimensional short-axis reformatted DICOM images of the left ventricle into regions of interest (ROIs) in accordance with American Heart Association (AHA) standards and is capable of creating nine further ROI subsegments. This includes separate endocardial, mid-ventricle, and epicardial layers. Image intensity values (Hounsfield unit) and relative myocardial thickness are quantitatively reported for each ROI and segment. Results: The algorithm allows comparison of the HU values at the same ROI locations between rest and stress. The reproducibility is very good; ICC 0.89 for rest images, 0.83 for stress images. The mean time for generating ROIs for the entire heart was 11 minutes versus 22 minutes for manual tracing. Conclusion: The algorithm reports parameters relevant for evaluation of stress perfusion CT studies and will allow more accurate and reproducible analysis in cardiac CT research. C1 [Liew, Gary; Ali, Nabeel; Do, Synho; Petranovic, Milena; Brady, Thomas; Hoffmann, Udo; Ghoshhajra, Brian] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Ali, Nabeel] Albany Med Coll, Albany, NY 12208 USA. [Cury, Ricardo] Baptist Cardiac & Vasc Inst, Miami, FL USA. RP Liew, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM gyhliew@gmail.com NR 10 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2013 VL 20 IS 10 BP 1301 EP 1305 DI 10.1016/j.acra.2013.07.004 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 228NX UT WOS:000325194600016 PM 24029063 ER PT J AU Freudenreich, O Kontos, N Querques, J AF Freudenreich, O. Kontos, N. Querques, J. TI Horror diagnosticus psychiatricus - the fear of expanding nosologies and overdiagnosis in psychiatry SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Letter C1 [Freudenreich, O.; Kontos, N.; Querques, J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Freudenreich, O (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM ofreudenreich@partners.org NR 2 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD OCT PY 2013 VL 128 IS 4 BP 322 EP 322 DI 10.1111/acps.12145 PG 1 WC Psychiatry SC Psychiatry GA 224WQ UT WOS:000324922700013 PM 23647103 ER PT J AU Tsai, AC Bangsberg, DR Bwana, M Haberer, JE Frongillo, EA Muzoora, C Kumbakumba, E Hunt, PW Martin, JN Weiser, SD AF Tsai, Alexander C. Bangsberg, David R. Bwana, Mwebesa Haberer, Jessica E. Frongillo, Edward A. Muzoora, Conrad Kumbakumba, Elias Hunt, Peter W. Martin, Jeffrey N. Weiser, Sheri D. TI How Does Antiretroviral Treatment Attenuate the Stigma of HIV? Evidence from a Cohort Study in Rural Uganda SO AIDS AND BEHAVIOR LA English DT Article DE Social stigma; Depression; Antiretroviral; therapy; Highly active; HIV; Uganda ID AIDS-RELATED STIGMA; SUB-SAHARAN AFRICA; SOUTH-AFRICA; MENTAL-HEALTH; ECONOMIC-IMPACT; FOOD INSECURITY; THERAPY; HIV/AIDS; PEOPLE; DEPRESSION AB Program implementers and qualitative researchers have described how increasing availability of HIV antiretroviral therapy (ART) is associated with improvements in psychosocial health and internalized stigma. To determine whether, and through what channels, ART reduces internalized stigma, we analyzed data from 262 HIV-infected, treatment-na < ve persons in rural Uganda followed from ART initiation over a median of 3.4 years. We fitted Poisson regression models with cluster-correlated robust estimates of variance, specifying internalized stigma as the dependent variable, adjusting for time on treatment as well as socio-demographic, clinical, and psychosocial variables. Over time on treatment, internalized stigma declined steadily, with the largest decline observed during the first 2 years of treatment. This trend remained statistically significant after multivariable adjustment (chi(2) = 28.3; P = 0.03), and appeared to be driven by ART-induced improvements in HIV symptom burden, physical and psychological wellbeing, and depression symptom severity. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Dept Psychiat, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.; Bangsberg, David R.; Haberer, Jessica E.] MGH Ctr Global Hlth, Boston, MA USA. [Tsai, Alexander C.; Bangsberg, David R.; Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.; Bwana, Mwebesa; Muzoora, Conrad; Kumbakumba, Elias] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Hunt, Peter W.; Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Martin, Jeffrey N.] UCSF, Dept Epidemiol & Biostat, San Francisco, CA USA. [Weiser, Sheri D.] UCSF, Ctr AIDS Prevent Studies, San Francisco, CA USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Dept Psychiat, Ctr Global Hlth, Room 1529-E3,100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI027763, P30 AI-027763]; NIMH NIH HHS [K23 MH-079713, K23 MH-079713-03S1, K23 MH-087228, K23 MH-096620, K23 MH079713, K23 MH087228, K23 MH096620, K24 MH-087227, K24 MH087227, R01 MH-054907, R01 MH054907] NR 60 TC 23 Z9 23 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2013 VL 17 IS 8 BP 2725 EP 2731 DI 10.1007/s10461-013-0503-3 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 226IB UT WOS:000325027600016 PM 23670710 ER PT J AU Tsai, AC Mimiaga, MJ Dilley, JW Hammer, GP Karasic, DH Charlebois, ED Sorensen, JL Safren, SA Bangsberg, DR AF Tsai, Alexander C. Mimiaga, Matthew J. Dilley, James W. Hammer, Gwendolyn P. Karasic, Dan H. Charlebois, Edwin D. Sorensen, James L. Safren, Steven A. Bangsberg, David R. TI Does Effective Depression Treatment Alone Reduce Secondary HIV Transmission Risk? Equivocal Findings from a Randomized Controlled Trial SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Depression; Antidepressive agents; Sexual behavior; Protected sex; Homeless persons ID ANTIDEPRESSANT MEDICATION TREATMENT; POISSON REGRESSION APPROACH; UNITED-STATES; MENTAL-HEALTH; SAN-FRANCISCO; INFECTED INDIVIDUALS; COLLABORATIVE CARE; SEXUAL-BEHAVIORS; FOOD INSECURITY; CLINICAL-TRIALS AB Depressed mood has been associated with HIV transmission risk behavior. To determine whether effective depression treatment could reduce the frequency of sexual risk behavior, we analyzed secondary outcome data from a 36-week, two-arm, parallel-design, randomized controlled trial, in which homeless and marginally housed, HIV-infected persons with comorbid depressive disorders were randomized to receive either: (a) directly observed treatment with the antidepressant medication fluoxetine, or (b) referral to a local public mental health clinic. Self-reported sexual risk outcomes, which were measured at 3, 6, and 9 months, included: total number of sexual partners, unprotected sexual intercourse, unprotected sexual intercourse with an HIV-uninfected partner or a partner of unknown serostatus, and transactional sex. Estimates from generalized estimating equations regression models did not suggest consistent reductions in sexual risk behaviors resulting from treatment. Mental health interventions may need to combine depression treatment with specific skills training in order to achieve durable impacts on HIV prevention outcomes. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.; Mimiaga, Matthew J.; Safren, Steven A.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Dilley, James W.; Karasic, Dan H.; Sorensen, James L.] Univ Calif San Francisco, Dept Psychiat, San Francisco Gen Hosp, San Francisco, CA USA. [Dilley, James W.] Alliance Hlth Project, San Francisco, CA USA. [Hammer, Gwendolyn P.] Calif Dept Publ Hlth, Communicable Dis Emergency Response Branch, Sacramento, CA USA. [Charlebois, Edwin D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA USA. [Safren, Steven A.] Fenway Hlth, Boston, MA USA. [Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Room 1529-E3,100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI027763, P30 AI060354, P30AI060354]; NIDA NIH HHS [U10 DA015815]; NIMH NIH HHS [K23 MH096620, K23MH096620, K24 MH087227, K24MH087227, R01 MH054907, R01 MH063011, R01MH054907, R01MH063011] NR 45 TC 9 Z9 9 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2013 VL 17 IS 8 BP 2765 EP 2772 DI 10.1007/s10461-013-0600-3 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 226IB UT WOS:000325027600020 PM 23975476 ER PT J AU Simoni, JM Wiebe, JS Sauceda, JA Huh, D Sanchez, G Longoria, V Bedoya, CA Safren, SA AF Simoni, Jane M. Wiebe, John S. Sauceda, John A. Huh, David Sanchez, Giselle Longoria, Virginia Bedoya, C. Andres Safren, Steven A. TI A Preliminary RCT of CBT-AD for Adherence and Depression Among HIV-Positive Latinos on the US-Mexico Border: The Nuevo Dia Study SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; ART adherence; Depression; CBT; Latino/Hispanic ID ANTIRETROVIRAL THERAPY ADHERENCE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; BEHAVIORAL INTERVENTIONS; INCREASE ADHERENCE; IMPROVES ADHERENCE; INFECTED PATIENTS; UNITED-STATES; BARRIERS; DISORDERS AB We conducted a preliminary RCT among 40 HIV-positive Latinos of Mexican descent on the U.S.-Mexico border who indicated imperfect adherence and depressive symptomatology. Participants were randomly assigned to culturally adapted cognitive-behavioral therapy for adherence and depression with an alarmed pillbox or usual care. Outcomes were depressive symptoms (self-report and blind clinician ratings), adherence (self-report and electronic pillbox), and biological markers. The intervention, delivered in English and Spanish, proved feasible and acceptable. Generalized estimating equations in intent-to-treat analyses showed some effects of "moderate" to "large" size, with maintenance over time. For example, intervention (vs. control) participants demonstrated at post-intervention a greater drop in BDI scores (OR = -3.64, p = 0.05) and greater adherence according to the electronic pillbox (OR = 3.78, p = 0.03). Biological markers indicated some relative improvement for CD4 count but not VL. The promising results suggest a larger trial to determine efficacy is warranted. C1 [Simoni, Jane M.; Huh, David] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Wiebe, John S.; Sauceda, John A.; Sanchez, Giselle; Longoria, Virginia] Univ Texas El Paso, Dept Psychol, El Paso, TX 79968 USA. [Bedoya, C. Andres; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Simoni, JM (reprint author), Univ Washington, Dept Psychol, 3909 W Stevens Way NE,Campus Box 351525, Seattle, WA 98195 USA. EM jsimoni@uw.edu OI Simoni, Jane/0000-0002-8711-1576; Huh, David/0000-0002-6357-4883 FU NIAID NIH HHS [P30 AI027757]; NIMH NIH HHS [1R34MH08674, K24 MH093243, R34 MH084674, R34MH084674-S1] NR 66 TC 22 Z9 22 U1 3 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2013 VL 17 IS 8 BP 2816 EP 2829 DI 10.1007/s10461-013-0538-5 PG 14 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 226IB UT WOS:000325027600026 PM 23812892 ER PT J AU Babson, KA Heinz, AJ Bonn-Miller, MO AF Babson, Kimberly A. Heinz, Adrienne J. Bonn-Miller, Marcel O. TI HIV Medication Adherence and HIV Symptom Severity: The Roles of Sleep Quality and Memory SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; AFRICAN-AMERICAN; UNITED-STATES; SUBSTANCE USE; OF-LIFE; INFECTION; WOMEN; DEPRESSION; MORTALITY; ADULTS AB The purpose of the current study was to examine the extent to which self-reported sleep quality, a clinically malleable factor, is associated with both HIV medication adherence and self-reported HIV symptom severity. In addition, we sought to examine whether sleep quality may explain the association between HIV medication adherence and symptom severity, as well as the role of self-reported memory functioning in terms of the above relations. This study took place from April 2010 to March 2012. Participants were 129 HIV-positive individuals who completed an ART pill count and series of structured clinical interviews and self-report questionnaires on sleep, memory, and HIV symptom severity. A series of regressions were conducted to test study hypotheses. After accounting for covariates (i.e., problematic alcohol, nicotine, and cannabis use, and mood disorder diagnosis), results indicated that self-reported sleep quality was associated with HIV medication adherence and self-reported HIV symptom severity, and that sleep quality partially mediated the relation between medication adherence and self-reported HIV symptom severity. In addition, memory functioning moderated the relation between self-reported sleep quality and HIV symptom severity, such that the interaction of poor sleep quality and relatively good memory functioning was associated with heightened self-reported HIV symptom severity. This study highlights the importance of assessing sleep and memory among HIV-infected individuals as they may represent treatment targets for those experiencing poor medication adherence or particularly severe HIV symptoms. Such information could lead to the inclusion of adjunct brief interventions to target sleep and memory functioning in order to reduce symptom severity among HIV-positive individuals with poor medication adherence. C1 [Babson, Kimberly A.; Heinz, Adrienne J.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA. [Babson, Kimberly A.; Heinz, Adrienne J.] Stanford Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Babson, KA (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM Kimberly.Babson@va.gov FU California HIV/AIDS Research Program IDEA Award [163836]; VA Clinical Science Research and Development (CSR&D) Career Development Award-2; Health Services Research and Development Service funds FX This work was supported, in part, by the following: A California HIV/AIDS Research Program IDEA Award (163836; Bonn-Miller), a VA Clinical Science Research and Development (CSR&D) Career Development Award-2 (Bonn-Miller), and Health Services Research and Development Service funds provided to Drs. Babson and Heinz. The expressed views do not necessarily represent those of the Department of Veterans Affairs. NR 58 TC 9 Z9 10 U1 2 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT 1 PY 2013 VL 27 IS 10 BP 544 EP 552 DI 10.1089/apc.2013.0221 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 229ME UT WOS:000325268600003 PM 24032625 ER PT J AU Tellalian, D Maznavi, K Bredeek, UF Hardy, WD AF Tellalian, David Maznavi, Khalid Bredeek, U. Fritz Hardy, W. David TI Pre-Exposure Prophylaxis (PrEP) for HIV Infection: Results of a Survey of HIV Healthcare Providers Evaluating Their Knowledge, Attitudes, and Prescribing Practices SO AIDS PATIENT CARE AND STDS LA English DT Article ID POSTEXPOSURE PROPHYLAXIS; INTERIM GUIDANCE; PREVENTION; MEN; IMPLEMENTATION; POPULATION; PERCEPTION; WOMEN; SEX; US AB Antiretroviral medications can be taken by HIV-negative persons to prevent HIV infection, also known as pre-exposure prophylaxis (PrEP). PrEP was first shown to be effective during the iPrEX study. We conducted a survey involving HIV healthcare providers to document their attitudes and prescribing practices about PrEP in response to this study. An online survey was completed by 189 members and credentialees of the American Academy of HIV Medicine between April 2011 and September 2011. Ninety percent of respondents were familiar with the results of the iPrEx study, and most (78%) were familiar with CDC's interim guidance regarding the use of PrEP in MSM. Only 19% of respondents had prescribed PrEP. The majority of PrEP prescribers were compliant with CDC interim guidance; however, only 61% screened for hepatitis B. Of PrEP prescribers, 78% prescribed to MSM, 31% to MSW, and 28% to WSM. Greatest concerns about prescribing PrEP included development of antiretroviral resistance (32%), potential increase in high-risk behavior, (22%) and poor medication adherence (21%). Fifty-eight percent stated that HIV serodiscordance within a relationship most influenced their decision to prescribe PrEP to the HIV-seronegative partner. This study demonstrates that, despite awareness of the efficacy of PrEP, its use is limited. Survey participants used PrEP most commonly in MSM; however, a significant percentage also prescribed PrEP to women. The best candidate for PrEP is felt to be individuals in an HIV-serodiscordant relationship. Limitations to our study included a low response rate, changes in the evidence base, and the novelty of PrEP. C1 [Tellalian, David; Hardy, W. David] Cedars Sinai Med Ctr, Dept Internal Med, Div Infect Dis, Los Angeles, CA 90048 USA. [Maznavi, Khalid] Torrance Mem Med Ctr, Torrance, CA USA. [Bredeek, U. Fritz] Metropolis Med, San Francisco, CA USA. [Hardy, W. David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Tellalian, D (reprint author), VA Greater Los Angeles, Infect Dis Sect IIIF, 11301 Wilshire Blvd,Bldg 500,Ste 4669, Los Angeles, CA 90073 USA. EM dmtellalian@yahoo.com NR 22 TC 42 Z9 42 U1 3 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT 1 PY 2013 VL 27 IS 10 BP 553 EP 559 DI 10.1089/apc.2013.0173 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 229ME UT WOS:000325268600004 PM 24053478 ER PT J AU Froehlich, JC Hausauer, BJ Rasmussen, DD AF Froehlich, Janice C. Hausauer, Brett J. Rasmussen, Dennis D. TI Combining Naltrexone and Prazosin in a Single Oral Medication Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism Treatment; Genetic Selection; Naltrexone; Prazosin ID DEPENDENCE-INDUCED INCREASES; RANDOMIZED CONTROLLED-TRIAL; PREFERRING P RATS; RECEPTOR ANTAGONIST; USE DISORDERS; ETHANOL; PREFERENCE; PLACEBO; MODEL; BLOCKADE AB BackgroundNaltrexone (NTX) is underutilized in clinical treatment settings because its efficacy is modest, and it is not effective for all alcoholics and, when it is effective, a significant number of alcoholics fail to maintain initial treatment gains and subsequently relapse to heavy drinking. This has slowed acceptance of NTX by the treatment community, and there is a clear need for additional treatments for alcoholism and alcohol use disorders. Given that NTX and prazosin can each reduce alcohol drinking in rats selectively bred for alcohol preference and high voluntary alcohol drinking (alcohol-preferring P rats), we tested whether a combination of NTX+prazosin is more effective in decreasing alcohol drinking than is either drug alone. MethodsP rats were given access to a 15% (v/v) alcohol solution for 2hours daily. Rats were fed NTX and prazosin, alone or in combination, prior to onset of the daily 2-hour alcohol access period for 4weeks and the effect of drug treatment on alcohol and water intake was assessed. ResultsDuring the first week of treatment, neither a low dose of NTX, nor prazosin, was effective in decreasing alcohol intake when each drug was administered alone, but combining the 2 drugs in a single medication significantly reduced alcohol intake. The combination was as effective as was a higher dose of NTX. Using a low dose of NTX in combination with prazosin may reduce the potential for undesirable side effects early in treatment which, in turn, may improve patient compliance and result in a more successful outcome when NTX is used for treating alcoholism and alcohol use disorders. ConclusionsCombining low-dose NTX and prazosin in a single medication may be more useful than is either drug alone for treating both inpatient and outpatient alcoholics and heavy drinkers early in the treatment process. C1 [Froehlich, Janice C.; Hausauer, Brett J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Froehlich, JC (reprint author), Indiana Univ Sch Med, 975 West Walnut St IB 448, Indianapolis, IN 46202 USA. EM jcfroehl@iupui.edu FU NIH [AA018604, AA07611, AA13881] FX We thank Dr. Ting-Kai Li and the Indiana Alcohol Research Center for supplying the selectively bred rats used in this study. This study was supported by NIH grants AA018604 (JCF and DDR), AA07611 (JCF), and AA13881 (DDR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Alcohol Abuse and Alcoholism or the National Institutes of Health. NR 55 TC 14 Z9 14 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2013 VL 37 IS 10 BP 1763 EP 1770 DI 10.1111/acer.12148 PG 8 WC Substance Abuse SC Substance Abuse GA 229KR UT WOS:000325263500017 PM 23875623 ER PT J AU Hoeppner, BB Paskausky, AL Jackson, KM Barnett, NP AF Hoeppner, Bettina B. Paskausky, Anna L. Jackson, Kristina M. Barnett, Nancy P. TI Sex Differences in College Student Adherence to NIAAA Drinking Guidelines SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE College Students; Alcohol; Drinking Guidelines; Sex Differences ID ALCOHOL-USE DISORDERS; NORMATIVE FEEDBACK; STEPPED CARE; RISK; CONSUMPTION; TRIAL; CONSEQUENCES; METAANALYSIS; POPULATION; PREVALENCE AB BackgroundExceeding nationally recommended drinking limits puts individuals at increased risk of experiencing harmful effects due to alcohol consumption. Both weekly and daily limits exist to prevent harm due to toxicity and intoxication, respectively. It remains unclear how well college students adhere to recommended limits, and whether their drinking is sensitive to the wider sex difference in weekly versus daily drinking limits. MethodsThis study used a daily-level, academic-year-long, multisite sample to describe adherence to NIAAA daily (no more than 4 drinks per day for men, 3 drinks per day for women) and weekly (no more than 14 drinks per week for men, 7 drinks per week for women) drinking guidelines, and to test for sex differences and time effects. College students (n=992; 58% female) reported daily drinking on a biweekly basis using web-based surveys throughout their first year of college. ResultsWomen exceeded weekly limits more frequently (15% of weeks [14 to 17%]) than men (12% [10 to 14%]). Women and men exceeded daily drinking limits similarly often (25 and 27%, respectively). In a generalized estimating equations analysis across all 18 biweekly assessments, adjusted for covariates and a linear trend over time, women were more likely to exceed weekly guidelines compared to men. Sex differences in exceeding daily limits were not significant. Over time, rates of exceeding limits declined for daily limits but only for men for weekly limits. ConclusionsFemale college students are more likely to exceed weekly alcohol intake limits than men. Furthermore, trends over time suggest that college students may be maturing out of heavy episodic drinking, but women may not mature out of harmful levels of weekly drinking. The observed disparity in risk for long-term health consequences may represent a missed opportunity for education and intervention. C1 [Hoeppner, Bettina B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA USA. [Paskausky, Anna L.] Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Jackson, Kristina M.; Barnett, Nancy P.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Hoeppner, BB (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM bhoepp-ner@partners.org FU National Institute on Alcohol Abuse and Alcoholism [R01AA013970]; National Institute on Drug Abuse grant [K01DA 027097] FX This study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (R01AA013970) and the National Institute on Drug Abuse grant (K01DA 027097). NR 34 TC 9 Z9 9 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2013 VL 37 IS 10 BP 1779 EP 1786 DI 10.1111/acer.12159 PG 8 WC Substance Abuse SC Substance Abuse GA 229KR UT WOS:000325263500019 PM 23682991 ER PT J AU Durazzo, TC Pennington, DL Schmidt, TP Mon, A Abe, C Meyerhoff, DJ AF Durazzo, Timothy C. Pennington, David L. Schmidt, Thomas P. Mon, Anderson Abe, Christoph Meyerhoff, Dieter J. TI Neurocognition in 1-Month-Abstinent Treatment-Seeking Alcohol-Dependent Individuals: Interactive Effects of Age and Chronic Cigarette Smoking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Use Disorders; Cigarette Smoking; Neurocognition; Alcohol Dependence; Age ID NATIONAL EPIDEMIOLOGIC SURVEY; DSM-IV ALCOHOL; PROCESSING SPEED; COGNITIVE IMPAIRMENT; ABSTINENT ALCOHOLICS; FEMALE ALCOHOLICS; UNITED-STATES; USE DISORDERS; CONSUMPTION; DEFICITS AB BackgroundIncreasing age and chronic cigarette smoking are independently associated with adverse effects on multiple aspects of neurocognition in those seeking treatment for alcohol use disorders. However, the potential interactive effects of age and cigarette smoking on neurocognition in early abstinent alcohol-dependent individuals (ALC) have not investigated. MethodsCross-sectional performances of never-smoking healthy comparison participants (nvsCOM; n=39) and 1-month-abstinent, treatment-seeking, never-smoking (nvsALC; n=30), former-smoking (fsALC; n=21), and actively smoking (asALC; n=68) ALC were compared on a comprehensive neurocognitive battery. Domains of functioning evaluated were cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions and working memory. Participants were between 26 and 71years of age at the time of assessment. ResultsasALC showed steeper age-related effects than nvsCOM on the domains of visuospatial learning, auditory-verbal memory, cognitive efficiency, executive functions, processing speed, and fine motor skills. In pairwise comparisons, fsALC and asALC performed more poorly than both nvsCOM and nvsALC on multiple domains; nvsCOM and nvsALC showed no significant differences. Domain scores for the ALC groups generally fell in the low-to-high-average range of functioning. A clinically significant level of impairment was apparent in only 25% of ALC participants on visuospatial learning, visuospatial memory, and fine motor skills domains. Measures of alcohol use or consumption were not significantly related to neurocognition in the ALC cohorts. ConclusionsThe age-related findings suggest that the combination of active chronic smoking and alcohol dependence in this 1-month-abstinent ALC cohort was associated with greater than normal age-related effects in multiple domains. In general, a low level of clinically significant impairment was observed in the alcohol-dependent participants. The findings from this study, in conjunction with previous research, strongly support smoking cessation interventions for those seeking treatment for alcohol and substance use disorders. C1 [Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Mon, Anderson; Abe, Christoph; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Pennington, David L.; Abe, Christoph; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114 M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu OI Abe, Christoph/0000-0002-1680-8480 FU National Institutes of Health [NIH DA24136, NIH AA10788] FX We thank Mary Rebecca Young, Kathleen Altieri, Ricky Chen, and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital, and Dr. David Pating, Karen Moise, and their colleagues at CDRP for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. This work was supported by the National Institutes of Health (NIH DA24136 to TCD and NIH AA10788 to DJM) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. NR 51 TC 8 Z9 8 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2013 VL 37 IS 10 BP 1794 EP 1803 DI 10.1111/acer.12140 PG 10 WC Substance Abuse SC Substance Abuse GA 229KR UT WOS:000325263500021 PM 23682867 ER PT J AU Lee, D Goodman, SG Fox, KAA DeYoung, JP Lai, CC Bhatt, DL Huynh, T Yan, RT Gallo, R Steg, PG Yan, AT AF Lee, Dana Goodman, Shaun G. Fox, Keith A. A. DeYoung, J. Paul Lai, Christopher C. Bhatt, Deepak L. Thao Huynh Yan, Raymond T. Gallo, Richard Steg, Ph Gabriel Yan, Andrew T. CA Global Registry Acute Coronary Eve Canadian Registry Acute Coronary E TI Prognostic significance of presenting blood pressure in non-ST-segment elevation acute coronary syndrome in relation to prior history of hypertension SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PROSPECTIVELY-DESIGNED OVERVIEWS; MAJOR CARDIOVASCULAR EVENTS; GLOBAL REGISTRY; RISK STRATIFICATION; HOSPITAL MORTALITY; INTERNATIONAL TRIAL; RANDOMIZED-TRIALS; LOWERING REGIMENS; GRACE AB Background Hypertension is a well-established risk factor for cardiovascular disease, whereas low systolic blood pressure (SBP) is a powerful adverse prognosticator in acute coronary syndrome. However, it is unclear whether the prognostic significance of low SBP differs in patients with versus without prior history of hypertension. We sought to investigate the relationships between presenting SBP, prior hypertension, antihypertensive medication use, and outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS). Methods Using data from GRACE/GRACE(2) and CANRACE, we stratified 10,337 patients with NSTEACS from 1999 to 2008 into 2 groups: those with and those without prior diagnosis of hypertension. We performed multivariable logistic regression analysis to assess the prognostic significance of prior hypertension on in-hospital mortality and tested for the interactions between prior hypertension, antihypertensive medication use, and presenting SBP. Results Compared with patients without prior hypertension (n = 3,732), those with prior hypertension (n = 6,605) were older; more likely to be female; and more frequently had diabetes, previous myocardial infarction, heart failure, renal insufficiency, and higher Killip class and GRACE risk scores on presentation. Patients with prior hypertension were more likely to be on antihypertensive medications before admission, to present with higher SBP, and to have heart failure or cardiogenic shock in hospital (6.0% vs 10.1%; P < .001). In-hospital mortality was higher among patients presenting with lower SBP but did not differ between the groups with and without prior hypertension. In multivariable analysis, neither prior hypertension (adjusted odds ratio = 1.15, 95% CI 0.78-1.70, P =.48) nor the number of antihypertensive medications used (P for trend = .84) was independently associated with in-hospital mortality. In contrast, SBP was a strong independent predictor of in-hospital mortality (adjusted odds ratio = 1.21 per 10 mm Hg lower, 1.15-1.27, P < .001). There was no significant interaction between SBP and prior hypertension (P for interaction = .62) or pre-admission antihypertensive medication use (P for interaction = .46) with respect to in-hospital mortality. Conclusion Low SBP on presentation, but not prior hypertension, was independently associated with in-hospital mortality in NSTEACS. The powerful prognostic value of SBP is similar regardless of a history of hypertension or pre-admission antihypertensive medication use. C1 [Lee, Dana; Goodman, Shaun G.; Yan, Andrew T.] St Michaels Hosp, Div Cardiol, Terrence Donnelly Heart Ctr, Toronto, ON M5B 1W8, Canada. [Lee, Dana; Goodman, Shaun G.; Yan, Raymond T.; Yan, Andrew T.] Univ Toronto, Toronto, ON, Canada. [Goodman, Shaun G.] Canadian Heart Res Ctr, Toronto, ON, Canada. [Fox, Keith A. A.] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. [DeYoung, J. Paul] Univ Ottawa, Cornwall Community Hosp, Ottawa, ON, Canada. [Lai, Christopher C.] Thunder Bay Reg Hlth Sci Ctr, Thunder Bay, ON, Canada. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, TIMI Study Grp, VA Boston Healthcare Syst, Boston, MA USA. [Thao Huynh] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Gallo, Richard] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Steg, Ph Gabriel] Univ Paris Diderot, AP HP, INSERM, U698, Paris, France. RP Yan, AT (reprint author), St Michaels Hosp, Div Cardiol, 30 Bond St,Room 6-030 Donnelly, Toronto, ON M5B 1W8, Canada. EM yana@smh.ca FU Heart and Stroke Foundation of Canada FX We thank Sue Francis, BA, for her assistance in the preparation of this manuscript. We are grateful to all the study investigators, coordinators, and patients who participated in GRACE, GRACE-2, and CANRACE. Dr Andrew Yan is supported by a New Investigator Award from the Heart and Stroke Foundation of Canada. NR 30 TC 6 Z9 6 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2013 VL 166 IS 4 BP 716 EP 722 DI 10.1016/j.ahj.2013.06.025 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 227EL UT WOS:000325092300026 PM 24093852 ER PT J AU Merchant, FM Zheng, H Bigger, T Steinman, R Ikeda, T Pedretti, RFE Salerno-Uriarte, JA Klersy, C Chan, PS Bartone, C Hohnloser, SH Ruskin, JN Armoundas, AA AF Merchant, Faisal M. Zheng, Hui Bigger, Thomas Steinman, Richard Ikeda, Takanori Pedretti, Roberto F. E. Salerno-Uriarte, Jorge A. Klersy, Catherine Chan, Paul S. Bartone, Cheryl Hohnloser, Stefan H. Ruskin, Jeremy N. Armoundas, Antonis A. TI A combined anatomic and electrophysiologic substrate based approach for sudden cardiac death risk stratification SO AMERICAN HEART JOURNAL LA English DT Article ID T-WAVE ALTERNANS; LEFT-VENTRICULAR DYSFUNCTION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; NONISCHEMIC DILATED CARDIOMYOPATHY; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; CORONARY-ARTERY-DISEASE; EJECTION FRACTION; PREDICTIVE-VALUE; ARRHYTHMIA VULNERABILITY AB Background Although left ventricular ejection fraction (LVEF) is the primary determinant for sudden cardiac death (SCD) risk stratification, in isolation, LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker strategy would provide more robust SCD risk stratification than LVEF alone. Methods We collected patient-level data (n = 3355) from 6 studies assessing the prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of the group was used for derivation (n = 2242) and one-third for validation (n = 1113). The discriminative capacity of the multivariable model was assessed using the area under the receiver-operating characteristic curve (c-index). The primary endpoint was SCD at 24 months. Results In the derivation cohort, 59 patients experienced SCD by 24 months. Stepwise selection suggested that a model based on 3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD risk prediction. In the derivation cohort, the c-index of the model was 0.817, which was significantly better than LVEF used as a single variable (0.637, P < .001). In the validation cohort, 36 patients experienced SCD by 24 months. The c-index of the model for predicting the primary endpoint was again significantly better than LVEF alone (0.774 vs 0.671, P = .020). Conclusions A multivariable model based on presence of coronary artery disease, LVEF and MTWA status provides significantly more robust SCD risk prediction than LVEF as a single risk marker. These findings suggest that multi-marker strategies based on different aspects of the electro-anatomic substrate may be capable of improving primary prevention implantable cardioverter-defibrillator treatment algorithms. C1 [Merchant, Faisal M.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Merchant, Faisal M.; Ruskin, Jeremy N.; Armoundas, Antonis A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Bigger, Thomas; Steinman, Richard] Columbia Univ, Div Cardiol, New York, NY USA. [Ikeda, Takanori] Toho Univ, Med Ctr, Dept Cardiovasc Med, Tokyo, Japan. [Pedretti, Roberto F. E.] IRCCS Fdn Salvatore Maugeri, Sci Inst Tradate, Div Cardiol, Tradate, Italy. [Salerno-Uriarte, Jorge A.] Univ Insubria, Osped Circolo, Dept Heart Sci, Varese, Italy. [Salerno-Uriarte, Jorge A.] Univ Insubria, Fdn Macchie, Varese, Italy. [Klersy, Catherine] Univ Pavia, IRCCS Policin S Matteo, Dept Biostat, I-27100 Pavia, Italy. [Chan, Paul S.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Chan, Paul S.] Univ Missouri, Kansas City, MO 64110 USA. [Bartone, Cheryl] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Hohnloser, Stefan H.] Goethe Univ Frankfurt, Dept Cardiol, Div Clin Electrophysiol, D-60054 Frankfurt, Germany. [Armoundas, Antonis A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org OI Klersy, Catherine/0000-0003-0314-8548 FU NCRR NIH HHS [UL1 RR025758, UL1 RR 025758]; NHLBI NIH HHS [K23 HL102224, K23HL102224]; NIA NIH HHS [1R21AG035128, R21 AG035128] NR 44 TC 3 Z9 3 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2013 VL 166 IS 4 BP 744 EP 752 DI 10.1016/j.ahj.2013.06.023 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 227EL UT WOS:000325092300030 PM 24093856 ER PT J AU Liu, SW Nagurney, JT Chang, YC Parry, BA Smulowitz, P Atlas, SJ AF Liu, Shan W. Nagurney, John T. Chang, Yuchiao Parry, Blair A. Smulowitz, Peter Atlas, Steven J. TI Frequent ED users: are most visits for mental health, alcohol, and drug-related complaints? SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; URBAN AB Study objective: To determine whether frequent emergency department (ED) users are more likely to make at least one and a majority of visits for mental health, alcohol, or drug-related complaints compared to non-frequent users. Methods: We performed a retrospective cohort study exploring frequent ED use and ED diagnosis at a single, academic hospital and included all ED patients between January 1 and December 31, 2010. We compared differences in ED visits with a primary International Classification of Diseases, 9th Revision visit diagnosis of mental health, alcohol or drug-related diagnoses between non-frequent users (<4 visits during previous 12-months) and frequent (repeat [4-7 visits], highly frequent [8-18 visits] and super frequent [>= 19 visits]) users in univariate and multivariable analyses. Results: Frequent users (2496/65201 [3.8%] patients) were more likely to make at least one visit associated with mental health, alcohol, or drug-related diagnoses. The proportion of patients with a majority of visits related to any of the three diagnoses increased from 5.8% among non-frequent users (3616/62705) to 9.4% among repeat users (181/1926), 13.1% among highly frequent users (62/473), and 25.8% (25/97 patients) in super frequent users. An increasing proportion of visits with alcohol-related diagnoses was observed among repeat, highly frequent, and super frequent users but was not found for mental health or drug-related complaints. Conclusion: Frequent ED users were more likely to make a mental health, alcohol or drug-related visit, but a majority of visits were only noted for those with alcohol-related diagnoses. To address frequent ED use, interventions focusing on managing patients with frequent alcohol-related visits may be necessary. (c) 2013 Elsevier Inc. All rights reserved. C1 [Liu, Shan W.; Nagurney, John T.; Parry, Blair A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chang, Yuchiao; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Smulowitz, Peter] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02115 USA. RP Liu, SW (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM Sliu1@partners.org NR 10 TC 15 Z9 15 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2013 VL 31 IS 10 BP 1512 EP 1515 DI 10.1016/j.ajem.2013.08.006 PG 4 WC Emergency Medicine SC Emergency Medicine GA 227RR UT WOS:000325132000018 PM 24035051 ER PT J AU Fondell, E Fitzgerald, KC Falcone, GJ O'Reilly, EJ Ascherio, A AF Fondell, Elinor Fitzgerald, Kathryn C. Falcone, Guido J. O'Reilly, Eilis J. Ascherio, Alberto TI Early-Onset Alopecia and Amyotrophic Lateral Sclerosis: A Cohort Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alopecia; amyotrophic lateral sclerosis; cohort studies; male-pattern baldness; motor neuron disease ID ANDROGEN RECEPTOR GENE; RISK; SMOKING; TDP-43; ALS; HYPOTHESIS; PREVALENCE; MUTATIONS; LENGTH; INDEX AB A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 4681 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (19922008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk 2.74, 95 confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (P-trend 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation. C1 [Fondell, Elinor; Fitzgerald, Kathryn C.; O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Falcone, Guido J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fondell, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM efondell@hsph.harvard.edu RI Falcone, Guido/L-2287-2016 OI Falcone, Guido/0000-0002-6407-0302 FU National Cancer Institute [P01 CA055075] FX This work was supported by the National Cancer Institute (grant P01 CA055075). NR 25 TC 4 Z9 5 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2013 VL 178 IS 7 BP 1146 EP 1149 DI 10.1093/aje/kwt096 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 227YN UT WOS:000325151700019 PM 23942216 ER PT J AU Madariaga, ML Michel, SG Tasaki, M Villani, V La Muraglia, GM Sihag, S Gottschall, J Farkash, EA Shimizu, A Allan, JS Sachs, DH Yamada, K Madsen, JC AF Madariaga, M. L. Michel, S. G. Tasaki, M. Villani, V. La Muraglia, G. M., II Sihag, S. Gottschall, J. Farkash, E. A. Shimizu, A. Allan, J. S. Sachs, D. H. Yamada, K. Madsen, J. C. TI Induction of Cardiac Allograft Tolerance Across a Full MHC Barrier in Miniature Swine by Donor Kidney Cotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Heart transplantation; kidney transplantation; miniature swine; tolerance ID TUBULAR EPITHELIAL-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; PLASMACYTOID DENDRITIC CELLS; RENAL-ALLOGRAFTS; T-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; TRANSPLANTATION TOLERANCE; INTERNATIONAL SOCIETY; IMMUNE-MECHANISMS; REGULATORY CELLS AB We have previously shown that tolerance of kidney allografts across a full major histocompatibility complex (MHC) barrier can be induced in miniature swine by a 12-day course of high-dose tacrolimus. However, that treatment did not prolong survival of heart allografts across the same barrier. We have now tested the effect of cotransplanting an allogeneic heart and kidney from the same MHC-mismatched donor using the same treatment regimen. Heart allografts (n=3) or heart plus kidney allografts (n=5) were transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. As expected, all isolated heart allografts rejected by postoperative day 40. In contrast, heart and kidney allografts survived for >200 days with no evidence of rejection on serial cardiac biopsies. Heart/kidney recipients lost donor-specific responsiveness in cell-mediated lympholysis and mixed-lymphocyte reaction assays, were free of alloantibody and exhibited prolonged survival of donor, but not third-party skin grafts. Late (>100 days) removal of the kidney allografts did not cause acute rejection of the heart allografts (n=2) and did not abrogate donor-specific unresponsiveness in vitro. While kidney-induced cardiac allograft tolerance (KICAT) has previously been demonstrated across a Class I disparity, these data demonstrate that this phenomenon can also be observed across the more clinically relevant full MHC mismatch. Elucidating the renal element(s) responsible for KICAT could provide mechanistic information relevant to the induction of tolerance in recipients of isolated heart allografts as well as other tolerance-resistant organs. C1 [Madariaga, M. L.; Michel, S. G.; Tasaki, M.; Villani, V.; La Muraglia, G. M., II; Sihag, S.; Gottschall, J.; Allan, J. S.; Sachs, D. H.; Yamada, K.; Madsen, J. C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Michel, S. G.] Univ Munich, Dept Cardiac Surg, Munich, Germany. [Farkash, E. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shimizu, A.] Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. [Allan, J. S.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Madsen, J. C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM jcmadsen@partners.org OI Villani, Vincenzo/0000-0002-6078-9766 FU National Heart, Lung, and Blood Institute [P01HL18646]; National Institute of Allergy and Infectious Disease of National Institutes of Health [U01AI94374]; Thoracic Surgery Foundation for Research Education; International Society for Heart & Lung Transplantation FX This work was supported in part by grants from the National Heart, Lung, and Blood Institute (P01HL18646) and the National Institute of Allergy and Infectious Disease (U01AI94374) of National Institutes of Health, and the Thoracic Surgery Foundation for Research & Education. M.L.M. is an Edward D. Churchill Surgical Research Fellow, Massachusetts General Hospital and recipient of a fellowship from the International Society for Heart & Lung Transplantation. We acknowledge C06RR020135-01 for construction of the facility utilized for production and maintenance of miniature swine and are indebted to Mr. J. Scott Arn for herd management and quality control typing. NR 42 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2013 VL 13 IS 10 BP 2558 EP 2566 DI 10.1111/ajt.12423 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 224ZN UT WOS:000324932200011 PM 24033991 ER PT J AU Porcheray, F Fraser, JW Gao, B McColl, A DeVito, J Dargon, I Helou, Y Wong, W Girouard, TC Saidman, SL Colvin, RB Palmisano, A Maggiore, U Vaglio, A Smith, RN Zorn, E AF Porcheray, F. Fraser, J. W. Gao, B. McColl, A. DeVito, J. Dargon, I. Helou, Y. Wong, W. Girouard, T. C. Saidman, S. L. Colvin, R. B. Palmisano, A. Maggiore, U. Vaglio, A. Smith, R. N. Zorn, E. TI Polyreactive Antibodies Developing Amidst Humoral Rejection of Human Kidney Grafts Bind Apoptotic Cells and Activate Complement SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antibody-mediated rejection; apoptosis; C4d; polyreactive antibodies ID RENAL-ALLOGRAFT REJECTION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CORONARY-ARTERY-DISEASE; ANTICARDIOLIPIN ANTIBODIES; ERYTHROCYTE C4D; TRANSPLANTATION; AUTOANTIBODIES; RECEPTOR-1; TOLERANCE; EXPOSURE AB Antibody mediated rejection (AMR) is associated with a variety of graft-reactive antibodies following kidney transplant. To characterize these antibodies, we immortalized 107 B cell clones from a patient with AMR. In a previous study, we showed that six clones were reacting to multiple self-antigens as well as to HLA and MICA for two of them, thus displaying a pattern of polyreactivity. We show here that all six polyreactive clones also reacted to apoptotic but not viable cells. More generally we observed a nearly perfect overlap between polyreactivity and reactivity to apoptotic cells. Functionally, polyreactive antibodies can activate complement, resulting in the deposition of C3d and C4d at the surface of target cells. Testing the serum of 88 kidney transplant recipients revealed a significantly higher IgG reactivity to apoptotic cells in AMR patients than in patients with stable graft function. Moreover, total IgG purified from AMR patients had increased complement activating properties compared to IgG from non-AMR patients. Overall, our studies show the development of polyreactive antibodies cross-reactive to apoptotic cells during AMR. Further studies are now warranted to determine their contribution to the detection of C4d in graft biopsies as well as their role in the pathophysiology of AMR. C1 [Porcheray, F.; Fraser, J. W.; Gao, B.; McColl, A.; DeVito, J.; Dargon, I.; Helou, Y.; Zorn, E.] Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gao, B.] Jilin Univ, Hosp 1, Transplant Ctr, Changchun 130023, Peoples R China. [Wong, W.] Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Boston, MA USA. [Girouard, T. C.; Saidman, S. L.; Colvin, R. B.; Smith, R. N.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Palmisano, A.; Maggiore, U.; Vaglio, A.] Univ Hosp Parma, Nephrol Unit, Parma, Italy. RP Zorn, E (reprint author), Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM ezorn@partners.org OI Vaglio, Augusto/0000-0002-3814-9172 FU Fahd and Nadia Alireza's Research Fund; Roche Organ Transplantation Research Foundation (ROTRF); National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases [DK083352] FX This work was supported by the Fahd and Nadia Alireza's Research Fund, the Roche Organ Transplantation Research Foundation (ROTRF) and the National Institute of Health, National Institute of Diabetes, Digestive and Kidney Diseases Grant DK083352. NR 34 TC 20 Z9 20 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2013 VL 13 IS 10 BP 2590 EP 2600 DI 10.1111/ajt.12394 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 224ZN UT WOS:000324932200014 PM 23919437 ER PT J AU Elias, N Kawai, T Ko, DSC Saidi, R Tolkoff-Rubin, N Wicky, S Cosimi, AB Hertl, M AF Elias, N. Kawai, T. Ko, D. S. C. Saidi, R. Tolkoff-Rubin, N. Wicky, S. Cosimi, A. B. Hertl, M. TI Native Portal Vein Embolization for Persistent Hyperoxaluria Following Kidney and Auxiliary Partial Liver Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Auxiliary liver transplantation; combined transplants; graft function; hypertrophy; hyperoxaluria; partial liver grafts ID TYPE-1; OXALOSIS AB Type 1 primary hyperoxaluria (PH1) causes renal failure, for which isolated kidney transplantation (KT) is usually unsuccessful treatment due to early oxalate stone recurrence. Although hepatectomy and liver transplantation (LT) corrects PH1 enzymatic defect, simultaneous auxiliary partial liver transplantation (APLT) and KT have been suggested as an alternative approach. APLT advantages include preservation of the donor pool and retention of native liver function in the event of liver graft loss. However, APLT relative mass may be inadequate to correct the defect. We here report the first case of native portal vein embolization (PVE) to increase APLT to native liver mass ratio (APLT/NLM-R). Following initial combined APLT-KT, both allografts functioned well, but oxalate plasma levels did not normalize. We postulated the inadequate APLT/NLM-R could be corrected by trans-hepatic native PVE. The resulting increased APLT/NLM-R decreased serum oxalate to normal levels within 1 month following PVE. We conclude that persistently elevated oxalate levels after combined APLT-KT for PH1 treatment, results from inadequate relative functional capacity. This can be reversed by partial native PVE to decrease portal flow to the native liver. This approach might be applicable to other scenarios where partial grafts have been transplanted to replace native liver function. C1 [Elias, N.; Kawai, T.; Ko, D. S. C.; Saidi, R.; Tolkoff-Rubin, N.; Cosimi, A. B.; Hertl, M.] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Elias, N.; Kawai, T.; Ko, D. S. C.; Saidi, R.; Tolkoff-Rubin, N.; Wicky, S.; Cosimi, A. B.; Hertl, M.] Harvard Univ, Sch Med, Boston, MA USA. [Wicky, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Elias, N (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. EM elias.nahel@mgh.harvard.edu NR 9 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2013 VL 13 IS 10 BP 2739 EP 2742 DI 10.1111/ajt.12381 PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 224ZN UT WOS:000324932200030 PM 23915277 ER PT J AU Ching, SN Liberman, MY Chemali, JJ Westover, MB Kenny, JD Solt, K Purdon, PL Brown, EN AF Ching, ShiNung Liberman, Max Y. Chemali, Jessica J. Westover, M. Brandon Kenny, Jonathan D. Solt, Ken Purdon, Patrick L. Brown, Emery N. TI Real-time Closed-loop Control in a Rodent Model of Medically Induced Coma Using Burst Suppression SO ANESTHESIOLOGY LA English DT Article ID REFRACTORY STATUS EPILEPTICUS; DELIVERY-SYSTEM CLADS(TM); QUANTITATIVE EEG ANALYSIS; BISPECTRAL INDEX; PERFORMANCE ASSESSMENT; PROPOFOL ANESTHESIA; GENERAL-ANESTHESIA; FEEDBACK-CONTROL; REMIFENTANIL; SURGERY AB Background: A medically induced coma is an anesthetic state of profound brain inactivation created to treat status epilepticus and to provide cerebral protection after traumatic brain injuries. The authors hypothesized that a closed-loop anesthetic delivery system could automatically and precisely control the electroencephalogram state of burst suppression and efficiently maintain a medically induced coma. Methods: In six rats, the authors implemented a closed-loop anesthetic delivery system for propofol consisting of: a computer-controlled pump infusion, a two-compartment pharmacokinetics model defining propofol's electroencephalogram effects, the burst-suppression probability algorithm to compute in real time from the electroencephalogram the brain's burst-suppression state, an online parameter-estimation procedure and a proportional-integral controller. In the control experiment each rat was randomly assigned to one of the six burst-suppression probability target trajectories constructed by permuting the burst-suppression probability levels of 0.4, 0.65, and 0.9 with linear transitions between levels. Results: In each animal the controller maintained approximately 60 min of tight, real-time control of burst suppression by tracking each burst-suppression probability target level for 15 min and two between-level transitions for 5-10 min. The posterior probability that the closed-loop anesthetic delivery system was reliable across all levels was 0.94 (95% CI, 0.77-1.00; n = 18) and that the system was accurate across all levels was 1.00 (95% CI, 0.84-1.00; n = 18). Conclusion: The findings of this study establish the feasibility of using a closed-loop anesthetic delivery systems to achieve in real time reliable and accurate control of burst suppression in rodents and suggest a paradigm to precisely control medically induced coma in patients. C1 [Ching, ShiNung; Liberman, Max Y.; Chemali, Jessica J.; Westover, M. Brandon; Kenny, Jonathan D.; Solt, Ken; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA. EM enb@neurostat.mit.edu OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health, Bethesda, Maryland [DP1-OD003646, ROI-GM10498, DP2-OD006454, K08-GM094394]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; Burroughs-Wellcome Fund, Durham, North Carolina [1010625] FX Support was provided by grants DP1-OD003646 (to Dr. Brown), ROI-GM10498 (to Dr. Brown), DP2-OD006454 (to Dr. Purdon), and K08-GM094394 (to Dr. Solt) from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Dr. Ching holds a Career Award at the Scientific Interface (1010625) from the Burroughs-Wellcome Fund, Durham, North Carolina. The first four authors contributed equally to this work. NR 49 TC 15 Z9 15 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2013 VL 119 IS 4 BP 848 EP 860 DI 10.1097/ALN.0b013e31829d4ab4 PG 13 WC Anesthesiology SC Anesthesiology GA 219AJ UT WOS:000324475400024 PM 23770601 ER PT J AU Fikry, K Bittner, EA AF Fikry, Karim Bittner, Edward A. TI Tegaderm (TM) Trauma in the Operating Room SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Fikry, Karim] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Fikry, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM kfikry@partners.org NR 3 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2013 VL 119 IS 4 BP 955 EP 955 DI 10.1097/ALN.0b013e31828e13be PG 1 WC Anesthesiology SC Anesthesiology GA 219AJ UT WOS:000324475400035 PM 23478484 ER PT J AU Ahn, Y Gorlinger, K Eikermann, M AF Ahn, Young Goerlinger, Klaus Eikermann, Matthias TI Multilevel Continuous Intercostal Nerve Block Catheter: A Viable Alternative to Thoracic Epidural for Multiple Rib Fractures? SO ANESTHESIOLOGY LA English DT Letter ID LIGHT TRANSMISSION AGGREGOMETRY; ELEVATED PLASMA-FIBRINOGEN; IMPEDANCE AGGREGOMETRY; CLOPIDOGREL TREATMENT; PLATELET REACTIVITY; THERAPY C1 [Ahn, Young; Goerlinger, Klaus; Eikermann, Matthias] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ahn, Y (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM meikermann@partners.org NR 15 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2013 VL 119 IS 4 BP 994 EP 995 DI 10.1097/ALN.0b013e3182a462b1 PG 2 WC Anesthesiology SC Anesthesiology GA 219AJ UT WOS:000324475400051 PM 24195886 ER PT J AU Forman, SA AF Forman, Stuart A. TI The Power of Unbiased Genetic Screens to Discover Novel Anesthetic Targets Reply SO ANESTHESIOLOGY LA English DT Letter ID SENSITIVITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM saforman@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2013 VL 119 IS 4 BP 996 EP 996 DI 10.1097/ALN.0b013e3182a46271 PG 1 WC Anesthesiology SC Anesthesiology GA 219AJ UT WOS:000324475400053 PM 24195888 ER PT J AU Qaseem, A Holty, JEC Owens, DK Dallas, P Starkey, M Shekelle, P AF Qaseem, Amir Holty, Jon-Erik C. Owens, Douglas K. Dallas, Paul Starkey, Melissa Shekelle, Paul CA Amer Coll Phys TI Management of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID POSITIVE AIRWAY PRESSURE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; CONTROLLED CROSSOVER TRIAL; TEMPERATURE-CONTROLLED-RADIOFREQUENCY; MANDIBULAR REPOSITIONING SPLINT; CORONARY-ARTERY-DISEASE; CHRONIC HEART-FAILURE; 7-YEAR FOLLOW-UP AB Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of obstructive sleep apnea (OSA) in adults. Methods: This guideline is based on published literature from 1966 to September 2010 that was identified by using MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A supplemental MEDLINE search identified additional articles through October 2012. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included cardiovascular disease (such as heart failure, hypertension, stroke, and myocardial infarction), type 2 diabetes, death, sleep study measures (such as the Apnea-Hypopnea Index), measures of cardiovascular status (such as blood pressure), measures of diabetes status (such as hemoglobin A(1c) levels), and quality of life. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. Recommendation 1: ACP recommends that all overweight and obese patients diagnosed with OSA should be encouraged to lose weight. (Grade: strong recommendation; low-quality evidence) Recommendation 2: ACP recommends continuous positive airway pressure treatment as initial therapy for patients diagnosed with OSA. (Grade: strong recommendation; moderate-quality evidence) Recommendation 3: ACP recommends mandibular advancement devices as an alternative therapy to continuous positive airway pressure treatment for patients diagnosed with OSA who prefer mandibular advancement devices or for those with adverse effects associated with continuous positive airway pressure treatment. (Grade: weak recommendation; low-quality evidence) C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Stanford Univ, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Virginia Tech Univ, Caril Sch Med, Roanoke, VA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall West, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org FU ACP operating budget FX Financial support for the development of this guideline comes exclusively from the ACP operating budget. NR 163 TC 49 Z9 53 U1 0 U2 18 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 2013 VL 159 IS 7 BP 471 EP U94 DI 10.7326/00030003-4819-159-7-201310010-00704 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 234FQ UT WOS:000325628000005 PM 24061345 ER PT J AU Maciejewski, ML Hanlon, JT AF Maciejewski, Matthew L. Hanlon, Joseph T. TI Underreporting Potentially Inappropriate Prescribing for Older Outpatients: Does It Matter? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID BEERS CRITERIA; MEDICATION USE; ADULTS; PEOPLE C1 [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Ctr Hlth Serv Res Primary Care, Durham Vet Affairs Med Ctr, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Sch Med, Durham, NC 27710 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot & Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA USA. RP Maciejewski, ML (reprint author), Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, 508 Fulton St,Mailstop 152, Durham, NC 27705 USA. FU NIA NIH HHS [K07 AG033174] NR 10 TC 0 Z9 0 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 2013 VL 159 IS 7 BP 496 EP U113 DI 10.7326/00030003-4819-159-7-201310010-00012 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 234FQ UT WOS:000325628000010 PM 24081290 ER PT J AU Chen, JQ Bao, Y Lee, J Murray, JL Litton, JK Xiao, L Zhou, R Wu, Y Shen, XY Zhang, H Sahin, AA Katz, RL Bondy, ML Berinstein, NL Hortobagyi, GN Radvanyi, LG AF Chen, J. Q. Bao, Y. Lee, J. Murray, J. L. Litton, J. K. Xiao, L. Zhou, R. Wu, Y. Shen, X. Y. Zhang, H. Sahin, A. A. Katz, R. L. Bondy, M. L. Berinstein, N. L. Hortobagyi, G. N. Radvanyi, L. G. TI Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; immunohistochemistry; prognostic marker; TRPS-1 ID TO-MESENCHYMAL TRANSITION; ESTROGEN-RECEPTOR; FINGER PROTEIN; MAMMARY-GLAND; CLAUDIN-LOW; E-CADHERIN; EXPRESSION; GENE; SUBTYPES; APOPTOSIS AB TRPS-1 is a new GATA transcription factor that is differentially expressed in breast cancer (BC) where it been found recently to regulate epithelial-to-mesenchymal transition (EMT). We carried out a quantitative immunohistochemistry (qIHC) analysis of TRPS-1 expression in 341 primary-stage I-III BC samples in relation to patient clinical characteristics as well as its prognostic value, especially in an estrogen receptor-positive (ER+) subgroup. Higher TRPS-1 expression was significantly associated with a number of clinical and pathological characteristics as well as with improved overall survival (OS) and disease-free survival (DFS). Among stage I/II ER+ BC patients who received endocrine therapy alone, those with high TRPS-1 expression had significantly longer OS and DFS. There was also a strong association between TRPS-1 levels and the EMT marker E-cadherin in the ER+ invasive ductal carcinoma cases. Analysis of gene expression data on a panel of BC lines found that TRPS-1 expression was low or absent in BC lines having enriched mesenchymal features. Our data indicated that TRPS-1 is an independent prognostic marker in early-stage BC and a new EMT marker that can distinguish patients with ER+ BC who will respond longer to adjuvant endocrine therapy. C1 [Chen, J. Q.; Bao, Y.; Murray, J. L.; Litton, J. K.; Hortobagyi, G. N.; Radvanyi, L. G.] UT MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX USA. [Chen, J. Q.; Bao, Y.; Radvanyi, L. G.] UT MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX USA. [Lee, J.] UT MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX USA. [Xiao, L.; Wu, Y.; Zhang, H.; Sahin, A. A.; Katz, R. L.] UT MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Xiao, L.] Shanghai Huadong Hosp, Dept Pathol, Shanghai, Peoples R China. [Zhou, R.; Bondy, M. L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Shen, X. Y.] Baylor Coll Med, Vet Adm Hosp, Dept Pathol, Houston, TX 77030 USA. [Berinstein, N. L.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. RP Radvanyi, LG (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Dept Melanoma Med Oncol, Box 904,1515 Holcombe Blvd, Houston, TX 77030 USA. EM lradvanyi@mdanderson.org FU Sanofi Pasteur Canada; Susan G. Komen for the Cure [KG080061]; National Institutes of Health (NIH) [1 P50 CA 116199-01, CA 16672] FX This work was supported in part by a research grant from Sanofi Pasteur Canada (LR), by Susan G. Komen for the Cure grant KG080061 (LR), and by the National Institutes of Health (NIH) grant 1 P50 CA 116199-01 (Breast Cancer SPORE grant), and NIH grant CA 16672 (Cancer Center Support Grant). NR 52 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2013 VL 24 IS 10 BP 2534 EP 2542 DI 10.1093/annonc/mdt190 PG 9 WC Oncology SC Oncology GA 227ZI UT WOS:000325153800012 PM 23729783 ER PT J AU Kobraei, EM Song, TH Mathisen, DJ Deshpande, V Mark, EJ AF Kobraei, Edward M. Song, Tae H. Mathisen, Douglas J. Deshpande, Vikram Mark, Eugene J. TI Immunoglobulin G4-Related Disease Presenting as an Obstructing Tracheal Mass: Consideration of Surgical Indications SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID IGG4-RELATED DISEASE AB Immunoglobulin G4 (IgG4)-related disease is increasingly recognized in many organs; however, none are described in detail is the trachea. In addition, the role of surgical intervention in the disease has yet to be fully defined. We describe a patient with IgG4-related airway disease presenting as a low tracheal mass, which was treated with tracheal resection and reconstruction. This novel presentation of the disease highlights the importance of including IgG4-related disease in the differential diagnosis of tracheal masses. Further, possible indications for surgical therapy are considered. As the full clinical spectrum of IgG4-related disease continues to evolve, so too must approaches to disease management. (c) 2013 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Div Thorac Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kobraei, EM (reprint author), 2 Hawthorne Pl,15J, Boston, MA 02114 USA. EM ekobraei@partners.org NR 8 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2013 VL 96 IS 4 BP E91 EP E93 DI 10.1016/j.athoracsur.2013.04.120 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 228AJ UT WOS:000325156800004 PM 24088500 ER PT J AU Li, J Yang, PA Wu, Q Li, H Ding, YN Hsu, HC Spalding, DM Mountz, JD AF Li, Jun Yang, PingAr Wu, Qi Li, Hao Ding, Yanna Hsu, Hui-Chen Spalding, David M. Mountz, John D. TI Death Receptor 5-Targeted Depletion of Interleukin-23-Producing Macrophages, Th17, and Th1/17 Associated With Defective Tyrosine Phosphatase in Mice and Patients With Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLONY-STIMULATING FACTOR; MOTH-EATEN MICE; COLLAGEN-INDUCED ARTHRITIS; DR5 MONOCLONAL-ANTIBODY; CYTOKINE GM-CSF; T-CELLS; SYNOVIAL FIBROBLASTS; EFFECTOR PHASE; T(H)17 CELLS; MUTANT MICE AB ObjectiveBidirectional interactions between granulocyte-macrophage colony-stimulating factor-positive (GM-CSF+) T cells and interferon regulatory factor 5-positive (IRF-5+) macrophages play a major role in autoimmunity. In the absence of SH2 domain-containing phosphatase 1 (SHP-1), GM-CSF-stimulated cells are resistant to death receptor (DR)-mediated apoptosis. The objective of this study was to determine whether TRA-8, an anti-DR5 agonistic antibody, can eliminate inflammatory macrophages and CD4 T cells in the SHP-1-deficient condition. MethodsUbiquitous Cre (Ubc.Cre) human/mouse-chimeric DR5-transgenic mice were crossed with viable SHP-1-defective motheaten (me(v)/me(v)) mice. TRA-8 was administered weekly for up to 4 weeks. The clinical scores, histopathologic severity, and macrophage and CD4 T cell phenotypes were evaluated. The role of TRA-8 in depleting inflammatory macrophages and CD4 T cells was also evaluated, using synovial fluid obtained from patients with rheumatoid arthritis (RA). ResultsThe levels of inflammatory macrophages (interleukin-23-positive [IL-23+] IRF-5+) and CD4 T cells (IL-17+ GM-CSF+) were elevated in me(v)/me(v) mice. In DR5-transgenic me(v)/me(v) mice, DR5 expression was up-regulated in these 2 cell populations. TRA-8 treatment depleted these cell populations and resulted in a significant reduction in inflammation and in the titers of autoantibodies. In synovial cells from patients with RA, the expression of IRF5 and DR5 was negatively correlated with the expression of PTPN6. TRA-8, but not TRAIL, suppressed RA inflammatory macrophages and Th17 cells under conditions in which the expression of SHP-1 is low. ConclusionIn contrast to TRAIL, which lacks the capability to counteract the survival signal in the absence of SHP-1, TRA-8 eliminated both IRF-5+ IL-23+ M1 macrophages and pathogenic GM-CSF+ IL-17+ CD4 T cells in a SHP-1-independent manner. The results of the current study suggest that TRA-8 can deplete inflammatory cell populations that result from a hyperactive GM-CSF/IRF-5 axis. C1 [Li, Jun; Yang, PingAr; Wu, Qi; Li, Hao; Ding, Yanna; Hsu, Hui-Chen; Spalding, David M.; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Wu, Qi; Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, SHEL 307,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jdmountz@uab.edu RI Li, Hao/N-7406-2015 OI Li, Hao/0000-0002-2171-8826 FU Arthritis Foundation; Lupus Research Institute; NIH [1R01-AI-083705, 1R01-AI-071110, P30-AR-48311, P30-AR-46031]; Rheumatology Research Foundation grant; Daiichi Sankyo Company, Ltd.; Department of Veterans Affairs [1I01BX000600-01]; University of Alabama at Birmingham Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory FX Supported by the Arthritis Foundation (grant to Dr. Li), the Lupus Research Institute (grant to Dr. Hsu), the NIH (grants 1R01-AI-083705 to Dr. Hsu and 1R01-AI-071110 to Dr. Mountz), a Rheumatology Research Foundation grant to Dr. Mountz, Daiichi Sankyo Company, Ltd. (grant to Dr. Mountz), and the Department of Veterans Affairs (Merit Review grant 1I01BX000600-01 to Dr. Mountz). Portions of the study were performed at the University of Alabama at Birmingham Rheumatic Diseases Core Center (Analytical Genomics and Transgenics Core, Comprehensive Flow Cytometry Core, and Analytic Imaging and Immunoreagents Core), supported by NIH grant P30-AR-48311, and the University of Alabama at Birmingham Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory, supported by NIH grant P30-AR-46031. NR 43 TC 6 Z9 6 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 IS 10 BP 2594 EP 2605 DI 10.1002/art.38057 PG 12 WC Rheumatology SC Rheumatology GA 227TE UT WOS:000325136600013 PM 23818173 ER PT J AU Anyanwu, CO Ang, CC Werth, VP AF Anyanwu, Cynthia O. Ang, Chia Chun Werth, Victoria P. TI Clinical Image: Oral mucosal involvement in bullous lupus SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID ERYTHEMATOSUS; RITUXIMAB C1 [Anyanwu, Cynthia O.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Anyanwu, CO (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. FU NIAMS NIH HHS [K24 AR002207] NR 3 TC 2 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 IS 10 BP 2622 EP 2622 DI 10.1002/art.38051 PG 1 WC Rheumatology SC Rheumatology GA 227TE UT WOS:000325136600016 PM 23780804 ER PT J AU Wang, JH New, JS Xie, ST Yang, PA Wu, Q Li, J Luo, B Ding, YN Druey, KM Hsu, HC Mountz, JD AF Wang, John H. New, James S. Xie, Shutao Yang, PingAr Wu, Qi Li, Jun Luo, Bao Ding, Yanna Druey, Kirk M. Hsu, Hui-Chen Mountz, John D. TI Extension of the Germinal Center Stage of B Cell Development Promotes Autoantibodies in BXD2 Mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYCLIC CITRULLINATED PEPTIDE; INDUCED CYTIDINE DEAMINASE; FOLLICULAR DENDRITIC CELLS; ANTIBODY CLASS SWITCH; RHEUMATOID-ARTHRITIS; PATHOGENIC AUTOANTIBODIES; PLASMA-CELLS; HAPTEN NP; T-CELLS AB ObjectiveRegulator of G protein signaling (RGS) proteins inhibit chemokine signaling by desensitizing G protein-coupled receptor signals. This study was undertaken to determine the mechanisms by which RGS13 promotes the generation of pathogenic autoantibodies in germinal centers (GCs), using BXD2-Rgs13(-/-) mice. MethodsConfocal and light microscopy imaging techniques were used to determine the location of cells that express RGS13 and activation-induced cytidine deaminase (AID) in the mouse spleen, and the number of plasmablasts. The levels of GC and plasma cell program transcripts in GC B cells were determined by real-time quantitative polymerase chain reaction (qPCR). Differential interleukin-17 (IL-17)-mediated expression of RGS13 in GC versus non-GC B cells was analyzed using A20 and 70Z/3 B cells. ResultsIn the spleens of BXD2 mice, RGS13 was mainly expressed by GC B cells and was stimulated by IL-17 but not IL-21. IL-17 up-regulated RGS13 in A20 GC cells but not 70Z/3 non-GC B cells. BXD2- Rgs13(-/-) mice exhibited smaller GCs and lower AID levels, suggesting lower somatic hypermutation and affinity maturation. However, GC B cells from BXD2- Rgs13(-/-) mice showed increased levels of IgM(bright) plasmablasts, up-regulation of the genes encoding plasma program, including interferon regulatory factor 4, B lymphocyte-induced maturation protein 1, and X-box binding protein 1 and the p-CREB target genes Fosb and Obf1, and down-regulation of the GC program genes Aid, Pax5, and Bach2 compared to BXD2 mice. BXD2-Rgs13(-/-) mice had lower titers of IgG autoantibodies and IgG deposits in the glomeruli, suggesting reduced autoantibody pathogenicity. ConclusionRGS13 deficiency is associated with a reduction in GC program genes and the exit of fewer pathogenic IgM plasmablasts in BXD2 mice. Our findings indicate that prolonged GC program, mediated by up-regulation of RGS13, enhances AID expression and enables the generation of pathogenic autoantibodies in autoreactive GCs. C1 [Wang, John H.; New, James S.; Xie, Shutao; Yang, PingAr; Wu, Qi; Li, Jun; Luo, Bao; Ding, Yanna; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Druey, Kirk M.] NIAID, NIH, Bethesda, MD 20892 USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, SHEL 307,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jdmountz@uab.edu FU NIH (National Institute of Allergy and Infectious Diseases) [1-AI-071110, ARRA 3R01-AI-71110-02S1, 1R01-AI-083705]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [P30-AR-048311, P30-AI-027767]; NIH (National Institute of Allergy and Infectious Diseases Intramural Research Program); Department of Veterans Affairs [1I01BX000600-01]; Rheumatology Research Foundation; Alliance for Lupus Research; Arthritis Foundation; Lupus Research Institute; NIH [P30-AR-048311, P30-A-I027767] FX Supported by the NIH (National Institute of Allergy and Infectious Diseases grants 1-AI-071110, ARRA 3R01-AI-71110-02S1, and 1R01-AI-083705, National Institute of Arthritis and Musculoskeletal and Skin Diseases grants P30-AR-048311 and P30-AI-027767, and the National Institute of Allergy and Infectious Diseases Intramural Research Program), the Department of Veterans Affairs (Merit Review grant 1I01BX000600-01), the Rheumatology Research Foundation (Within Our Reach grant), the Alliance for Lupus Research, the Arthritis Foundation, and the Lupus Research Institute. Flow cytometry and confocal imaging data acquisition were performed at the University of Alabama at Birmingham Comprehensive Flow Cytometry Core (supported by NIH grants P30-AR-048311 and P30-A-I027767) and Analytic Imaging and Immunoreagents Core (supported by NIH grant P30-AR-048311). NR 48 TC 9 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 IS 10 BP 2703 EP 2712 DI 10.1002/art.38059 PG 10 WC Rheumatology SC Rheumatology GA 227TE UT WOS:000325136600026 PM 23818250 ER PT J AU Kang, D Carruth, RW Kim, M Schlachter, SC Shishkov, M Woods, K Tabatabaei, N Wu, T Tearney, GJ AF Kang, DongKyun Carruth, Robert W. Kim, Minkyu Schlachter, Simon C. Shishkov, Milen Woods, Kevin Tabatabaei, Nima Wu, Tao Tearney, Guillermo J. TI Endoscopic probe optics for spectrally encoded confocal microscopy SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID DOUBLE-CLAD FIBER; BARRETTS-ESOPHAGUS; LASER ENDOMICROSCOPY; IN-VIVO; COUPLER; VIDEO AB Spectrally encoded confocal microscopy (SECM) is a form of reflectance confocal microscopy that can achieve high imaging speeds using relatively simple probe optics. Previously, the feasibility of conducting large-area SECM imaging of the esophagus in bench top setups has been demonstrated. Challenges remain, however, in translating SECM into a clinically-useable device; the tissue imaging performance should be improved, and the probe size needs to be significantly reduced so that it can fit into luminal organs of interest. In this paper, we report the development of new SECM endoscopic probe optics that addresses these challenges. A custom water-immersion aspheric singlet (NA = 0.5) was developed and used as the objective lens. The water-immersion condition was used to reduce the spherical aberrations and specular reflection from the tissue surface, which enables cellular imaging of the tissue deep below the surface. A custom collimation lens and a small-size grating were used along with the custom aspheric singlet to reduce the probe size. A dual-clad fiber was used to provide both the single- and multi- mode detection modes. The SECM probe optics was made to be 5.85 mm in diameter and 30 mm in length, which is small enough for safe and comfortable endoscopic imaging of the gastrointestinal tract. The lateral resolution was 1.8 and 2.3 mu m for the single- and multi- mode detection modes, respectively, and the axial resolution 11 and 17 mu m. SECM images of the swine esophageal tissue demonstrated the capability of this device to enable the visualization of characteristic cellular structural features, including basal cell nuclei and papillae, down to the imaging depth of 260 mu m. These results suggest that the new SECM endoscopic probe optics will be useful for imaging large areas of the esophagus at the cellular scale in vivo. (c) 2013 Optical Society of America C1 [Kang, DongKyun; Carruth, Robert W.; Kim, Minkyu; Schlachter, Simon C.; Shishkov, Milen; Woods, Kevin; Tabatabaei, Nima; Wu, Tao; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kang, DongKyun; Carruth, Robert W.; Kim, Minkyu; Schlachter, Simon C.; Shishkov, Milen; Woods, Kevin; Tabatabaei, Nima; Wu, Tao; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kim, Minkyu] Univ Tokyo, Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan. [Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kang, D (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM gtearney@partners.org FU Nine Point Medical, Cambridge, MA; Nine Point Medical FX This research was supported by a sponsored research agreement with Nine Point Medical, Cambridge, MA. Dr. Schlachter is currently with Nine Point Medical. Dr. Woods is currently with Emory University Hospital, Atlanta, GA. Dr. Tearney receives sponsored research from Nine Point Medical. Drs. Shishkov and Tearney consult for Nine Point Medical. Massachusetts General Hospital has a licensing arrangement with Ninepoint Medical. Drs. Kang, Carruth, Schlachter, Shishkov, and Tearney have the rights to receive royalty payments as part of this licensing arrangement. NR 20 TC 12 Z9 13 U1 0 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD OCT 1 PY 2013 VL 4 IS 10 BP 1925 EP 1936 DI 10.1364/BOE.4.001925 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 227UN UT WOS:000325140800012 PM 24156054 ER PT J AU Vinegoni, C Lee, S Feruglio, PF Marzola, P Nahrendorf, M Weissleder, R AF Vinegoni, Claudio Lee, Sungon Feruglio, Paolo Fumene Marzola, Pasquina Nahrendorf, Matthias Weissleder, Ralph TI Sequential average segmented microscopy for high signal-to-noise ratio motion-artifact-free in vivo heart imaging SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB In vivo imaging is often severely compromised by cardiovascular and respiratory motion. Highly successful motion compensation techniques have been developed for clinical imaging (e.g. magnetic resonance imaging) but the use of more advanced techniques for intravital microscopy is largely unexplored. Here, we implement a sequential cardiorespiratory gating scheme (SCG) for averaged microscopy. We show that SCG is very efficient in eliminating motion artifacts, is highly practical, enables high signal-to-noise ratio (SNR) in vivo imaging, and yields large field of views. The technique is particularly useful for high-speed data acquisition or for imaging scenarios where the fluorescence signal is not significantly above noise or background levels. (c) 2013 Optical Society of America C1 [Vinegoni, Claudio; Lee, Sungon; Feruglio, Paolo Fumene; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio; Lee, Sungon; Feruglio, Paolo Fumene; Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Lee, Sungon] Korea Inst Sci & Technol, Interact & Robot Res Ctr, Seoul, South Korea. [Marzola, Pasquina] Univ Verona, Dept Comp Sci, I-37134 Verona, Italy. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000044C]; Institute of Biomedical Engineering [R01EB006432]; National Institutes of Health [P01 AI54904] FX This project was funded in part by Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (under Contract No. HHSN268201000044C), and from the Institute of Biomedical Engineering (R01EB006432), and National Institutes of Health P01 AI54904. NR 17 TC 8 Z9 8 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD OCT 1 PY 2013 VL 4 IS 10 BP 2095 EP 2106 DI 10.1364/BOE.4.002095 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 227UN UT WOS:000325140800025 PM 24156067 ER PT J AU McKee, AC Stern, RA Nowinski, CJ Stein, TD Alvarez, VE Daneshvar, DH Lee, HS Wojtowicz, SM Hall, G Baugh, CM Riley, DO Kubilus, CA Cormier, KA Jacobs, MA Martin, BR Abraham, CR Ikezu, T Reichard, RR Wolozin, BL Budson, AE Goldstein, LE Kowall, NW Cantu, RC AF McKee, Ann C. Stern, Robert A. Nowinski, Christopher J. Stein, Thor D. Alvarez, Victor E. Daneshvar, Daniel H. Lee, Hyo-Soon Wojtowicz, Sydney M. Hall, Garth Baugh, Christine M. Riley, David O. Kubilus, Caroline A. Cormier, Kerry A. Jacobs, Matthew A. Martin, Brett R. Abraham, Carmela R. Ikezu, Tsuneya Reichard, Robert Ross Wolozin, Benjamin L. Budson, Andrew E. Goldstein, Lee E. Kowall, Neil W. Cantu, Robert C. TI The spectrum of disease in chronic traumatic encephalopathy. SO BRAIN LA English DT Correction C1 [McKee, Ann C.; Stein, Thor D.; Cormier, Kerry A.; Budson, Andrew E.; Kowall, Neil W.] VA Boston Healthcare Syst, US Dept Vet Affairs, Boston, MA 02130 USA. [McKee, Ann C.; Stern, Robert A.; Nowinski, Christopher J.; Alvarez, Victor E.; Daneshvar, Daniel H.; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Jacobs, Matthew A.; Goldstein, Lee E.; Cantu, Robert C.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. [McKee, Ann C.; Stern, Robert A.; Lee, Hyo-Soon; Kubilus, Caroline A.; Abraham, Carmela R.; Ikezu, Tsuneya; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [McKee, Ann C.; Stern, Robert A.; Nowinski, Christopher J.; Alvarez, Victor E.; Daneshvar, Daniel H.; Lee, Hyo-Soon; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Jacobs, Matthew A.; Ikezu, Tsuneya; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.; Stein, Thor D.; Goldstein, Lee E.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Stern, Robert A.; Cantu, Robert C.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Nowinski, Christopher J.; Cantu, Robert C.] Sports Legacy Inst, Waltham, MA 02451 USA. [Hall, Garth] Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. [Martin, Brett R.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Ikezu, Tsuneya; Wolozin, Benjamin L.] Boston Univ, Sch Publ Hlth, Dept Pharmacol, Boston, MA 02118 USA. [Abraham, Carmela R.] Boston Univ, Sch Publ Hlth, Dept Biochem, Boston, MA 02118 USA. [Reichard, Robert Ross] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Opthamol, Boston, MA 02118 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Biomed Engn, Boston, MA 02118 USA. [Cantu, Robert C.] Emerson Hosp, Dept Neurosurg, Concord, MA 01742 USA. RP McKee, AC (reprint author), VA Boston Healthcare Syst, US Dept Vet Affairs, Boston, MA 02130 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 1 TC 0 Z9 0 U1 7 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2013 VL 136 AR e255 DI 10.1093/brain/awt051 PN 10 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 228DU UT WOS:000325166500006 ER PT J AU Cesne, AL Judson, I Maki, R Grosso, F Schuetze, S Mehren, MV Chawla, SP Demetri, GD Nieto, A Tanovic, A Blay, JY AF Cesne, A. L. Judson, I. Maki, R. Grosso, F. Schuetze, S. Mehren, M. V. Chawla, S. P. Demetri, G. D. Nieto, A. Tanovic, A. Blay, J-Y TI Trabectedin is a feasible treatment for soft tissue sarcoma patients regardless of patient age: a retrospective pooled analysis of five phase II trials SO BRITISH JOURNAL OF CANCER LA English DT Article ID EUROPEAN ORGANIZATION; PROGNOSTIC-FACTORS; CANCER; ECTEINASCIDIN-743; CHEMOTHERAPY; ET-743; LIPOSARCOMA; IFOSFAMIDE; ANTITUMOR; EFFICACY AB Background: This retrospective pooled analysis assessed the effect of age on the efficacy and safety of trabectedin in young and elderly patients with recurrent advanced soft tissue sarcoma (STS). Methods: Data from 350 adults with STS treated in five phase II trials with trabectedin were divided in the younger (< 60 years; n = 267) and the older cohort (>= 60 years; n = 83). Results: The response rate did not differ with age (younger: 10.1% vs elderly 9.6%). No significant differences were found in median progression-free survival (PFS) in younger (2.5 months) and older (3.7 months) cohort with a comparable PFS rates at 3 (45.1% vs 55.1%) and 6 months (29.5% vs 36.4%). Similar median overall survival was observed in both cohorts (13.0 vs 14.0 months). Reversible neutropenia and aspartate aminotransferase/alanine aminotransferase elevation were the most common abnormalities. A higher incidence of grade 3/4 neutropenia (43.6% vs 60.2%) and fatigue (6.3% vs 14.4%) was observed in older patients. In 24 patients aged >= 70 years, no significant differences in efficacy or safety outcomes were found. Conclusion: This analysis demonstrated that trabectedin is a feasible treatment in young and elderly patients with STS, with meaningful clinical benefits and an acceptable safety profile, essential in palliative treatment of elderly patients. C1 [Cesne, A. L.] Inst Gustave Roussy, Dept Med, FR-94805 Villejuif, France. [Judson, I.] Royal Marsden Hosp, Inst Canc Res, Div Med, London SW3 6JJ, England. [Judson, I.] Royal Marsden Hosp, Sarcoma Unit, London SW3 6JJ, England. [Maki, R.] Mt Sinai Hosp NY, Dept Med & Paediat, New York, NY 10029 USA. [Grosso, F.] IRCCS Fdn, Natl Canc Inst, Dept Canc Med, Adult Sarcoma Med Treatment Unit, I-20133 Milan, Italy. [Schuetze, S.] Univ Michigan, Ctr Comprehens Canc, Dept Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Mehren, M. V.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Chawla, S. P.] Sarcoma Oncol Ctr, Dept Med Oncol, Santa Monica, CA 90403 USA. [Demetri, G. D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Canc & Sarcoma Ctr, Boston, MA 02115 USA. [Nieto, A.] PharmaMar, Clin Dev, Colmenar Viejo 28770, Madrid, Spain. [Tanovic, A.] Parc Cient Barcelona, PharmaMar, Med Affairs, Barcelona 08028, Spain. [Blay, J-Y] Ctr Leon Berard, Dept Med, F-69008 Lyon, France. RP Blay, JY (reprint author), Ctr Leon Berard, Dept Med, 28 Rue Laennec, F-69008 Lyon, France. EM jean-yves.blay@lyon.unicancer.fr RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU PharmaMar, Madrid, Spain; Janssen Research and Development, LLC, Raritan, NJ, USA FX This pooled analysis and all five completed phase II trials were supported by funding from PharmaMar, Madrid, Spain and Janssen Research and Development, LLC, Raritan, NJ 08869, USA. NR 28 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 1 PY 2013 VL 109 IS 7 BP 1717 EP 1724 DI 10.1038/bjc.2013.524 PG 8 WC Oncology SC Oncology GA 228UM UT WOS:000325216700002 PM 24022187 ER PT J AU Klitgaard, JL Koefoed, K Geisler, C Gadeberg, OV Frank, DA Petersen, J Jurlander, J Pedersen, MW AF Klitgaard, Josephine L. Koefoed, Klaus Geisler, Christian Gadeberg, Ole V. Frank, David A. Petersen, Jorgen Jurlander, Jesper Pedersen, Mikkel W. TI Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD5; chronic lymphocytic leukaemia; antibody combinations; complement-dependent cytotoxicity; epitope binning ID GROWTH-FACTOR RECEPTOR; HUMAN B-LYMPHOCYTES; T-CELLS; HUMAN CD5; PHASE-I; RITUXIMAB; LYMPHOMA; CANCER; OFATUMUMAB; THERAPY AB The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single mAbs and combinations of two mAbs against non-overlapping epitopes on human CD5. The results demonstrated that combinations of two mAbs significantly increased the level of CDC compared to the single mAbs, while no enhancement of ADCC was seen with anti-CD5 mAb combinations. High levels of CDC and ADCC correlated with low levels of Ab-induced CD5 internalization and degradation. Importantly, an anti-CD5 mAb combination enhanced CDC of CLL cells when combined with the anti-CD20 mAbs rituximab and ofatumumab as well as with the anti-CD52 mAb alemtuzumab. These results suggest that an anti-CD5 mAb combination inducing CDC and ADCC may be effective alone, in combination with mAbs against other targets or combined with chemotherapy for CLL and other CD5-expressing haematological or lymphoid malignancies. C1 [Klitgaard, Josephine L.; Koefoed, Klaus; Petersen, Jorgen; Pedersen, Mikkel W.] Symphogen AS, DK-2800 Lyngby, Denmark. [Klitgaard, Josephine L.; Geisler, Christian; Jurlander, Jesper] Rigshosp, Dept Haematol L4042, DK-2100 Copenhagen, Denmark. [Gadeberg, Ole V.] Vejle Sygehus, Dept Haematol, Vejle, Denmark. [Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Frank, David A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Frank, David A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Pedersen, MW (reprint author), Symphogen AS, DK-2800 Lyngby, Denmark. EM mwp@symphogen.com RI Pedersen, Mikkel/A-2071-2014 OI Pedersen, Mikkel/0000-0001-5711-9051 FU Frk. Amalie Jorgensens Mindelegat; Karl Bruuns legat; Ole Vissings Fond FX We thank Mrs. Lisbeth Lundbye Jacobsen for assistance with collection of CLL patient samples from Vejle Hospital, and Mrs. Yasmin Aktar for assistance with blood-drawing from healthy individuals. Helle Jane Jacobsen, PhD, is thanked for advice on the cytotoxicity assays. This work was supported by Frk. Amalie Jorgensens Mindelegat, Karl Bruuns legat and Ole Vissings Fond. NR 50 TC 10 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2013 VL 163 IS 2 BP 182 EP 193 DI 10.1111/bjh.12503 PG 12 WC Hematology SC Hematology GA 229HB UT WOS:000325251700006 PM 23927424 ER PT J AU Lu, KH Skates, S Hernandez, MA Bedi, D Bevers, T Leeds, L Moore, R Granai, C Harris, S Newland, W Adeyinka, O Geffen, J Deavers, MT Sun, CC Horick, N Fritsche, H Bast, RC AF Lu, Karen H. Skates, Steven Hernandez, Mary A. Bedi, Deepak Bevers, Therese Leeds, Leroy Moore, Richard Granai, Cornelius Harris, Steven Newland, William Adeyinka, Olasunkanmi Geffen, Jeremy Deavers, Michael T. Sun, Charlotte C. Horick, Nora Fritsche, Herbert Bast, Robert C., Jr. TI A 2-Stage Ovarian Cancer Screening Strategy Using the Risk of Ovarian Cancer Algorithm (ROCA) Identifies Early-Stage Incident Cancers and Demonstrates High Positive Predictive Value SO CANCER LA English DT Article DE ovarian cancer screening; CA125; cancer screening; transvaginal ultrasound; positive predictive value ID MARKERS AB BACKGROUNDA 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS). METHODSA single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). RESULTSA total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval=12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval=99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. CONCLUSIONSROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer. Cancer 2013;119:3454-3461.. (c) 2013 American Cancer Society. This study evaluated a 2-stage ovarian cancer screening strategy incorporating the Risk of Ovarian Cancer Algorithm (ROCA). ROCA identified early-stage incident cases with excellent specificity and highlights the potential for implementing effective strategies for the early detection of ovarian cancer in postmenopausal women. C1 [Lu, Karen H.; Sun, Charlotte C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Skates, Steven; Horick, Nora] Harvard Univ, Massachusetts Gen Hosp, Biostat Ctr, Boston, MA USA. [Hernandez, Mary A.; Fritsche, Herbert; Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Off Translat Res, Houston, TX 77030 USA. [Bedi, Deepak] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Bevers, Therese] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Leeds, Leroy] OGA Med Ctr, Houston, TX USA. [Moore, Richard; Granai, Cornelius] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Harris, Steven] OB GYN Associates Dallas, Dallas, TX USA. [Newland, William] Iowa Clin, Womens Clin, W Des Moines, IA USA. [Adeyinka, Olasunkanmi] Univ Texas Family Phys, Houston, TX USA. [Geffen, Jeremy] Geffen Canc Ctr & Res Inst, Vero Beach, FL USA. [Deavers, Michael T.] Univ Texas MD Anderson Canc Ctr, Dept Pathol & Clin Pathol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Lu, KH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Unit 1362,1515 Holcombe Blvd, Houston, TX 77030 USA. EM khlu@mdanderson.org RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU MD Anderson SPORE in Ovarian Cancer NCI [P50 CA83639]; Bioinformatics Shared Resources of the MD Anderson CCSG NCI [P30 CA16672]; National Foundation for Cancer Research FX This study was supported by funds from the MD Anderson SPORE in Ovarian Cancer NCI P50 CA83639, the Bioinformatics Shared Resources of the MD Anderson CCSG NCI P30 CA16672, the National Foundation for Cancer Research, philanthropic support from Golfers Against Cancer, the Tracey Jo Wilson Foundation, the Mossy Foundation, the Norton family, and Stuart and Gaye Lynn Zarrow. NR 7 TC 34 Z9 37 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2013 VL 119 IS 19 BP 3454 EP 3461 DI 10.1002/cncr.28183 PG 8 WC Oncology SC Oncology GA 224XK UT WOS:000324925500008 PM 23983047 ER PT J AU Odejide, OO Cronin, AM DeAngelo, DJ Bernazzoli, ZA Jacobson, JO Rodig, SJ LaCasce, AS Mazeika, TJ Earles, KD Abel, GA AF Odejide, Oreofe O. Cronin, Angel M. DeAngelo, Daniel J. Bernazzoli, Zachary A. Jacobson, Joseph O. Rodig, Scott J. LaCasce, Ann S. Mazeika, Teresa J. Earles, Kristofer D. Abel, Gregory A. TI Improving the Quality of Bone Marrow Assessment Impact of Operator Techniques and Use of a Specimen Preparation Checklist SO CANCER LA English DT Article DE bone marrow aspiration; bone marrow biopsy; leukemia; lymphoma ID SURGICAL SAFETY CHECKLIST; B-CELL LYMPHOMA; BIOPSY DEVICE; ASPIRATION; POPULATION; TREPHINES; PAIN AB BACKGROUNDSuccessful bone marrow assessment is essential to the diagnosis and staging of hematologic malignancies. The objective of this study was to determine whether specific operator techniques and/or use of a specimen preparation checklist could impact the quality of bone marrow assessment by reducing the frequency of nonspicular aspirates, small cores, and nondiagnostic samples. METHODSAll bone marrow biopsies performed at the Dana-Farber Cancer Institute from April, 2012 to September, 2012 were eligible for inclusion. Six operator techniques were linked with specimen quality in a preintervention cohort. Next, a specimen preparation checklist was implemented, and outcomes were compared from the preintervention and postintervention cohorts. RESULTSIn total, 830 procedures performed by 41 operators were prospectively observed and analyzed. In the preintervention cohort (n=413), no operator technique was associated with specimen quality in multivariable models accounting for patient characteristics and operator. Compared with the preintervention cohort, in multivariable analyses, the postintervention cohort (n=417) had decreased odds of nondiagnostic specimens (odds ratio, 0.49; 95% confidence interval, 0.28-0.87; P=.01) and core lengths 1 cm (odds ratio, 0.67; 95% confidence interval, 0.50-0.90; P=.009), but there was no significant difference in spicularity. CONCLUSIONSVariation in the operator techniques studied did not have an impact on specimen quality, but implementation of a specimen preparation checklist significantly improved core length and frequency of diagnostic samples. Cancer 2013;119:3472-3478.. (c) 2013 American Cancer Society. Implementation of a specimen preparation checklist significantly improved core length and diagnostic yield of bone marrow specimens. Variation in operator techniques did not differentially affect the quality of bone marrow assessment. C1 [Odejide, Oreofe O.; Cronin, Angel M.; Earles, Kristofer D.; Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02215 USA. [DeAngelo, Daniel J.; Bernazzoli, Zachary A.; Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Leukemia, Boston, MA 02215 USA. [Jacobson, Joseph O.] Dana Farber Canc Inst, Div Qual & Safety, Dept Med Oncol, Boston, MA 02215 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [LaCasce, Ann S.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Lymphoma, Boston, MA 02215 USA. [Mazeika, Teresa J.] Dana Farber Canc Inst, Dept Nursing & Patient Care Serv, Boston, MA 02215 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu NR 28 TC 5 Z9 5 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2013 VL 119 IS 19 BP 3472 EP 3478 DI 10.1002/cncr.28249 PG 7 WC Oncology SC Oncology GA 224XK UT WOS:000324925500010 PM 23921812 ER PT J AU Huang, RY Rahman, R Hamdan, A Kane, C Chen, C Norden, AD Reardon, DA Mukundun, S Wen, PY AF Huang, Raymond Y. Rahman, Rifaquat Hamdan, Alhafidz Kane, Caroline Chen, Christina Norden, Andrew D. Reardon, David A. Mukundun, Srinivasan Wen, Patrick Y. TI Recurrent Glioblastoma Volumetric Assessment and Stratification of Patient Survival With Early Posttreatment Magnetic Resonance Imaging in Patients Treated With Bevacizumab SO CANCER LA English DT Article DE glioblastoma; bevacizumab; magnetic resonance imaging; volumetric analysis; survival ID TUMOR SIZE; MALIGNANT GLIOMAS; PLUS IRINOTECAN; BRAIN-TUMORS; 3D; CRITERIA; 2D; ANGIOGENESIS; MULTIFORME AB BACKGROUNDDespite a high radiographic response rate in patients with recurrent glioblastoma following bevacizumab therapy, survival benefit has been relatively modest. We assess whether tumor volume measurements based on baseline and early posttreatment MRI can stratify patients in terms of progression-free survival (PFS) and overall survival (OS). METHODSBaseline (-4 +/- 4 days) and posttreatment (30 +/- 6 days) MRI exams of 91 patients with recurrent glioblastoma treated with bevacizumab were retrospectively evaluated for volume of enhancing tumor as well as volume of the T2/FLAIR hyperintensity. Overall survival (OS) and progression-free survival (PFS) were assessed using volume parameters in a Cox regression model adjusted for significant clinical parameters. RESULTSIn univariable analysis, residual tumor volume, percentage change in tumor volume, steroid change from baseline to posttreatment scan, and number of recurrences were associated with both OS and PFS. With dichotomization by sample median of 52% change of enhancing volume can stratify OS (52 weeks vs. 31 weeks, P=.013) and PFS (21 weeks vs. 12 weeks, P=.009). Residual enhancing volume, dichotomized by sample median of 7.8 cm(3), can also stratify for OS (64 weeks vs. 28 weeks, P<.001) and PFS (21 weeks vs. 12 weeks, P=.036). CONCLUSIONSVolumetric percentage change and absolute early posttreatment volume of enhancing tumor can stratify survival for patients with recurrent glioblastoma receiving bevacizumab therapy. Cancer 2013;119:3479-3488.. (c) 2013 American Cancer Society. Volumetric percentage change and absolute early posttreatment volume of enhancing tumor can stratify survival for patients with recurrent glioblastoma initiated on bevacizumab. A volumetric approach may be used to identify patients most likely to have a durable benefit from bevacizumab therapy. C1 [Huang, Raymond Y.; Mukundun, Srinivasan] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Rahman, Rifaquat; Chen, Christina] Harvard Univ, Sch Med, Boston, MA USA. [Hamdan, Alhafidz; Kane, Caroline; Norden, Andrew D.; Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 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 FU Amgen; AstraZeneca; Boehringer Ingelheim; Esai; Exelixis; Genentech/Roche; Geron; MEdimmune; Merck; Novartis; Sanofi-Aventis; Vascular Biogenics FX Dr. Wen has served on the board of Merck, Novartis, EMD, Genentech, and Serono; has received payment for lectures, including serving on speakers bureau for Merck, Genentech/Roche, and GlaxoSmithKline; and has received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Esai, Exelixis, Genentech/Roche, Geron, MEdimmune, Merck, Novartis, Sanofi-Aventis, and Vascular Biogenics. Dr. Norden has been a consultant for Parexel and Brigham and Women's Hospital TIMI research group. Dr. Reardon has been a consultant for Genentech/Roche and has served on an advisory board for Genentech. NR 24 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2013 VL 119 IS 19 BP 3479 EP 3488 DI 10.1002/cncr.28210 PG 10 WC Oncology SC Oncology GA 224XK UT WOS:000324925500011 PM 23821555 ER PT J AU Lipshultz, SE Lipsitz, SR Kutok, JL Miller, TL Colan, SD Neuberg, DS Stevenson, KE Fleming, MD Sallan, SE Franco, VI Henkel, JM Asselin, BL Athale, UH Clavell, LA Michon, B Laverdiere, C Larsen, E Kelly, KM Silverman, LB AF Lipshultz, Steven E. Lipsitz, Stuart R. Kutok, Jeffery L. Miller, Tracie L. Colan, Steven D. Neuberg, Donna S. Stevenson, Kristen E. Fleming, Mark D. Sallan, Stephen E. Franco, Vivian I. Henkel, Jacqueline M. Asselin, Barbara L. Athale, Uma H. Clavell, Luis A. Michon, Bruno Laverdiere, Caroline Larsen, Eric Kelly, Kara M. Silverman, Lewis B. TI Impact of Hemochromatosis Gene Mutations on Cardiac Status in Doxorubicin-Treated Survivors of Childhood High-Risk Leukemia SO CANCER LA English DT Article DE cardiotoxicity; doxorubicin; hemochromatosis; leukemia; pediatrics ID ACUTE LYMPHOBLASTIC-LEUKEMIA; IDIOPATHIC DILATED CARDIOMYOPATHY; HEREDITARY HEMOCHROMATOSIS; PEDIATRIC-PATIENTS; ONCOLOGY-GROUP; IRON OVERLOAD; HFE MUTATIONS; UNITED-STATES; CHILDREN; CANCER AB BACKGROUNDDoxorubicin is associated with progressive cardiac dysfunction, possibly through the formation of doxorubicin-iron complexes leading to free-radical injury. The authors determined the frequency of hemochromatosis (HFE) gene mutations associated with hereditary hemochromatosis and their relationship with doxorubicin-associated cardiotoxicity in survivors of childhood high-risk acute lymphoblastic leukemia. METHODSPeripheral blood was tested for 2 common HFE allelic variants: C282Y and H63D. Serum cardiac troponin-T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), which are biomarkers of cardiac injury and cardiomyopathy, respectively, were assayed during therapy. Left ventricular (LV) structure and function were assessed with echocardiography. RESULTSA total of 184 patients had DNA results for at least 1 variant, and 167 had DNA results for both: 24% carried H63D and 10% carried C282Y. Heterozygous C282Y genotype was associated with multiple elevations in cTnT concentrations (P=.039), but not NT-proBNP. At a median of 2.2 years (range, 1.0 years-3.6 years) after diagnosis, the mean Z-scores for LV fractional shortening (-0.71 [standard error (SE), 0.25]; P=.008), mass (-0.84 [SE, 0.17]; P<.001), and end-systolic (-4.36 [SE, 0.26], P<.001) and end-diastolic (-0.68 [SE, 0.25]; P=.01) posterior wall thickness were found to be abnormal in children with either allele (n=32). Noncarriers (n=63) also were found to have below-normal LV mass (-0.45 [SE, 0.15]; P=.006) and end-systolic posterior wall thickness (-4.06 [SE, 0.17]; P<.001). Later follow-up demonstrated similar results. CONCLUSIONSDoxorubicin-associated myocardial injury was associated with C282Y HFE carriers. Although LV mass and wall thickness were found to be abnormally low overall, they were even lower in HFE carriers, who also had reduced LV function. Screening newly diagnosed cancer patients for HFE mutations may identify those at risk for doxorubicin-induced cardiotoxicity. Cancer 2013;119:3555-3562.. (c) 2013 American Cancer Society. Doxorubicin is associated with progressive cardiac dysfunction, possibly by forming doxorubicin-iron complexes leading to free-radical injury. In the current study, doxorubicin-associated myocardial injury was associated with carriers of the C282Y allele, a common allelic variant of hemochromatosis, among long-term survivors of childhood high-risk acute lymphoblastic leukemia. C1 [Lipshultz, Steven E.; Miller, Tracie L.; Franco, Vivian I.; Henkel, Jacqueline M.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Lipshultz, Steven E.; Miller, Tracie L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Biostat Serv, Boston, MA 02115 USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Colan, Steven D.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA. [Neuberg, Donna S.; Stevenson, Kristen E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fleming, Mark D.] Harvard Univ, Sch Med, Dept Pathol, Boston Childrens Hosp, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Asselin, Barbara L.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. [Athale, Uma H.] McMaster Univ, Dept Pediat, Hamilton, ON, Canada. [Clavell, Luis A.] San Jorge Childrens Hosp, Dept Pediat, San Juan, PR USA. [Michon, Bruno] Univ Hosp Quebec, Dept Pediat Hematol Oncol, Quebec City, PQ, Canada. [Laverdiere, Caroline] Hop St Justine, Dept Pediat, Montreal, PQ H3T 1C5, Canada. [Larsen, Eric] Maine Childrens Canc Program, Div Pediat Hematol Oncol, Portland, ME USA. [Kelly, Kara M.] Columbia Univ, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY 10027 USA. RP Lipshultz, SE (reprint author), Univ Miami, Miller Sch Med, Dept Pediat, Med Campus MCCD D820,1601 NW 12th Ave,9th Fl, Miami, FL 33136 USA. EM slipshultz@med.miami.edu FU National Institutes of Health [HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, HD80002]; Children's Cardiomyopathy Foundation; Women's Cancer Association of the University of Miami; Lance Armstrong Foundation; STOP Children's Cancer Foundation; Scott Howard Fund; Michael Garil Fund FX Supported in part by grants from the National Institutes of Health (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, and HD80002), the Children's Cardiomyopathy Foundation, the Women's Cancer Association of the University of Miami, the Lance Armstrong Foundation, the STOP Children's Cancer Foundation, the Scott Howard Fund, and the Michael Garil Fund. NR 40 TC 31 Z9 31 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2013 VL 119 IS 19 BP 3555 EP 3562 DI 10.1002/cncr.28256 PG 8 WC Oncology SC Oncology GA 224XK UT WOS:000324925500020 PM 23861158 ER PT J AU Lui, KO Zangi, L Silva, EA Bu, L Sahara, M Li, RA Mooney, DJ Chien, KR AF Lui, Kathy O. Zangi, Lior Silva, Eduardo A. Bu, Lei Sahara, Makoto Li, Ronald A. Mooney, David J. Chien, Kenneth R. TI Driving vascular endothelial cell fate of human multipotent Isl1(+) heart progenitors with VEGF modified mRNA SO CELL RESEARCH LA English DT Article DE cardiovascular progenitors; endothelial cells; Isl1; mRNA; VEGF-A ID GROWTH-FACTOR; MYOCARDIAL ANGIOGENESIS; CORONARY-ARTERIES; GENE; LINEAGES; VESSEL; BLOOD; SPECIFICATION; CONTRIBUTES; EXPRESSION AB Distinct families of multipotent heart progenitors play a central role in the generation of diverse cardiac, smooth muscle and endothelial cell lineages during mammalian cardiogenesis. The identification of precise paracrine signals that drive the cell-fate decision of these multipotent progenitors, and the development of novel approaches to deliver these signals in vivo, are critical steps towards unlocking their regenerative therapeutic potential. Herein, we have identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT-ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, and clonal assays documented its ability to drive endothelial specification of human embryonic stem cell (ESC)-derived Isl1(+) progenitors in a VEGF receptor-dependent manner. Human Isl1-ECs (endothelial cells differentiated from hESC-derived ISL1(+) progenitors) resemble OFT-ECs in terms of expression of the cardiac endothelial progenitor- and endocardial cell-specific genes, confirming their organ specificity. To determine whether VEGF-A might serve as an in vivo cell-fate switch for human ESC-derived Isl1-ECs, we established a novel approach using chemically modified mRNA as a platform for transient, yet highly efficient expression of paracrine factors in cardiovascular progenitors. Overexpression of VEGF-A promotes not only the endothelial specification but also engraftment, proliferation and survival (reduced apoptosis) of the human Isl1(+) progenitors in vivo. The large-scale derivation of cardiac-specific human Isl1-ECs from human pluripotent stem cells, coupled with the ability to drive endothelial specification, engraftment, and survival following transplantation, suggest a novel strategy for vascular regeneration in the heart. C1 [Lui, Kathy O.; Bu, Lei; Sahara, Makoto; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lui, Kathy O.; Zangi, Lior; Bu, Lei; Sahara, Makoto; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 01238 USA. [Lui, Kathy O.; Bu, Lei; Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Pokfulam, Hong Kong, Peoples R China. [Zangi, Lior] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Silva, Eduardo A.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Silva, Eduardo A.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Li, Ronald A.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY 10029 USA. [Chien, Kenneth R.] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden. RP Lui, KO (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM kathyolui@fas.harvard.edu; kenneth.chien@ki.se RI Lui, Kathy O./E-4883-2015; Silva, Eduardo/M-2711-2015 OI Lui, Kathy O./0000-0002-1616-3643; Silva, Eduardo/0000-0003-3173-7622 FU NIH [U01H100408, U01HL098166]; Croucher Foundation Fellowship FX This study was supported by NIH U01H100408 and U01HL098166. KOL was supported by the Croucher Foundation Fellowship. NR 42 TC 29 Z9 29 U1 3 U2 15 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD OCT PY 2013 VL 23 IS 10 BP 1172 EP 1186 DI 10.1038/cr.2013.112 PG 15 WC Cell Biology SC Cell Biology GA 229OY UT WOS:000325278000008 PM 24018375 ER PT J AU Brent, BK Thermenos, HW Keshavan, MS Seidman, LJ AF Brent, Benjamin K. Thermenos, Heidi W. Keshavan, Matcheri S. Seidman, Larry J. TI Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia A Review of Structural MRI Findings SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review DE Schizophrenia; Structural MRI; Genetic high-risk; Prodrome; Early-onset schizophrenia; Childhood-onset schizophrenia ID ULTRA-HIGH-RISK; SUPERIOR TEMPORAL GYRUS; ANTERIOR CINGULATE CORTEX; CORTICAL BRAIN-DEVELOPMENT; CAVUM SEPTI PELLUCIDI; GENETIC HIGH-RISK; CHILDHOOD-ONSET; MAGNETIC-RESONANCE; PREFRONTAL CORTEX; 1ST-EPISODE PSYCHOSIS AB This article reviews the literature on structural magnetic resonance imaging findings in pediatric and young adult populations at clinical or genetic high-risk for schizophrenia and early-onset schizophrenia. The implications of this research are discussed for understanding the pathophysiology of schizophrenia and for early intervention strategies. The evidence linking brain structural changes in prepsychosis development and early-onset schizophrenia with disruptions of normal neurodevelopmental processes during childhood or adolescence is described. Future directions are outlined for research to address knowledge gaps regarding the neurobiological basis of brain structural abnormalities in schizophrenia and to improve the usefulness of these abnormalities for preventative interventions. C1 [Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.; Seidman, Larry J.] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. [Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Brent, Benjamin K.; Thermenos, Heidi W.; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Thermenos, Heidi W.] Athinoula A Martinos Imaging Ctr, Charlestown, MA 02129 USA. RP Brent, BK (reprint author), Beth Israel Deaconess Med Ctr, Dept Psychiat, 330 Brookline Ave, Boston, MA 02215 USA. EM bbrent@bidmc.harvard.edu FU NCRR NIH HHS [KL2 RR 025757, KL2 RR025757]; NIMH NIH HHS [L30 MH091727, MH065571, MH081928, MH092840, R01 MH065571, R21 MH092840, U01 MH081928]; PHS HHS [78113, KO2 01180, R01 64023] NR 168 TC 24 Z9 28 U1 13 U2 36 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 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD OCT PY 2013 VL 22 IS 4 BP 689 EP + DI 10.1016/j.chc.2013.06.003 PG 28 WC Psychiatry SC Psychiatry GA 228MP UT WOS:000325191200011 PM 24012081 ER PT J AU Boekholdt, SM Arsenault, BJ Hovingh, GK Mora, S Pedersen, TR LaRosa, JC Welch, KMA Amarenco, P DeMicco, DA Tonkin, AM Sullivan, DR Kirby, A Colhoun, HM Hitman, GA Betteridge, DJ Durrington, PN Clearfield, MB Downs, JR Gotto, AM Ridker, PM Kastelein, JJP AF Boekholdt, S. Matthijs Arsenault, Benoit J. Hovingh, G. Kees Mora, Samia Pedersen, Terje R. LaRosa, John C. Welch, K. M. A. Amarenco, Pierre DeMicco, David A. Tonkin, Andrew M. Sullivan, David R. Kirby, Adrienne Colhoun, Helen M. Hitman, Graham A. Betteridge, D. John Durrington, Paul N. Clearfield, Michael B. Downs, John R. Gotto, Antonio M., Jr. Ridker, Paul M. Kastelein, John J. P. TI Levels and Changes of HDL Cholesterol and Apolipoprotein A-I in Relation to Risk of Cardiovascular Events Among Statin-Treated Patients A Meta-Analysis SO CIRCULATION LA English DT Article DE apolipoproteins; cardiovascular diseases; high-density lipoprotein cholesterol; meta-analysis ID DENSITY-LIPOPROTEIN CHOLESTEROL; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; HIGH-DOSE ATORVASTATIN; PRIMARY PREVENTION; LDL CHOLESTEROL; THERAPY; ATHEROSCLEROSIS; ASSOCIATION; SIMVASTATIN AB Background It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk. Methods and Results We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97). Conclusions Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction. C1 [Arsenault, Benoit J.; Hovingh, G. Kees; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Arsenault, Benoit J.; Hovingh, G. Kees; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Mora, Samia; Ridker, Paul M.] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Pedersen, Terje R.] Oslo Univ Hosp, Ctr Prevent Med, Ulleval, Norway. [Pedersen, Terje R.] Univ Oslo, N-0316 Oslo, Norway. [LaRosa, John C.] SUNY Hlth Sci Ctr, Brooklyn, NY USA. [Welch, K. M. A.] Rosalind Franklin Univ Med & Sci, N Chicago, IL USA. [Amarenco, Pierre] Hop Xavier Bichat, Dept Neurol, Paris, France. [Amarenco, Pierre] Hop Xavier Bichat, Stroke Ctr, Paris, France. [DeMicco, David A.] Global Pharmaceut Pfizer, New York, NY USA. [Tonkin, Andrew M.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Sullivan, David R.] Univ Sydney, Royal Prince Alfred Hosp, Dept Biochem, Sydney, NSW 2006, Australia. [Sullivan, David R.] Univ Sydney, Royal Prince Alfred Hosp, Lipid Clin, Sydney, NSW 2006, Australia. [Kirby, Adrienne] Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW 2006, Australia. [Colhoun, Helen M.] Univ Dundee, Med Res Inst, Dundee, Scotland. [Hitman, Graham A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Diabet, London, England. [Betteridge, D. John] Royal Free & Univ Coll Med Sch, Dept Med, London WC1E 6BT, England. [Durrington, Paul N.] Univ Manchester, Sch Biomed, Manchester, Lancs, England. [Clearfield, Michael B.] Touro Univ, Mare Isl, CA USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Downs, John R.] South Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. [Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA. RP Kastelein, JJP (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM j.j.kastelein@amc.uva.nl RI Boekholdt, Matthijs/G-7562-2014; OI Colhoun, Helen/0000-0002-8345-3288 FU Veni grant from the Netherlands Organisation for Scientific Research (NWO) [91612122)]; National Heart, Lung, and Blood Institute [R01HL117861] FX This study was not supported by any funding. The contributing trials were funded by their respective sponsors. Dr Hovingh is funded by a Veni grant (project number 91612122) from the Netherlands Organisation for Scientific Research (NWO). Dr Mora is funded by a National Heart, Lung, and Blood Institute grant (number R01HL117861). The sponsors of the contributing trials provided the requested data. They did not play any role in the statistical analysis, interpretation of the data, or the decision to submit the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 31 TC 61 Z9 64 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 1 PY 2013 VL 128 IS 14 BP 1504 EP 1512 DI 10.1161/CIRCULATIONAHA.113.002670 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 228WB UT WOS:000325221500011 PM 23965489 ER PT J AU Myers, AP AF Myers, Andrea P. TI New Strategies in Endometrial Cancer: Targeting the PI3K/mTOR Pathway-The Devil Is in the Details SO CLINICAL CANCER RESEARCH LA English DT Article ID NOVO PYRIMIDINE SYNTHESIS; PHASE-II TRIAL; GERMLINE MUTATIONS; TUMOR-SUPPRESSOR; PROTEIN-KINASES; COWDEN DISEASE; HIGH-FREQUENCY; CARCINOMA; PTEN; PTEN/MMAC1 AB Endometrial cancer is the most common gynecologic malignancy in the developed world and affects approximately 40,000 women in the United States each year. The phosphoinositide 3-kinase (PI3K) signaling pathway regulates key aspects of cancer biology including glucose uptake and metabolism, cellular growth, and survival. Endometrial cancers harbor the highest rates of PI3K pathway alterations reported to date. The PI3K pathway is highly druggable and several classes of agents are in clinical development including rapalogs, pan-PI3K inhibitors, PI3K isoform-specific inhibitors, dual PI3K/mTOR catalytic inhibitors, mTOR-specific catalytic inhibitors, and AKT inhibitors. It has been 10 years since the initiation of the first studies of rapalogs as anticancer agents. There are more than 20 registered clinical trials of PI3K/mTOR inhibitors as single agents or in therapeutic combinations for the treatment of endometrial cancers. What have we learned from the completed studies? What can we expect to learn from ongoing studies? What should we anticipate moving forward? (C) 2013 AACR. C1 [Myers, Andrea P.] Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, Gynecol Oncol Program, Boston, MA 02115 USA. [Myers, Andrea P.] Beth Israel Deaconess Canc Ctr, Dept Med, Div Signal Transduct, Boston, MA 02115 USA. RP Myers, AP (reprint author), Novartis Inst BioMed Res Inc, Oncol Translat Med, 220 Massachusetts Ave, Cambridge, MA 02139 USA. EM andrea.myers@novartis.com FU Stand Up To Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation [SU2C-AACR-DT 0209] FX This work was supported by a Stand Up To Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT 0209). NR 60 TC 19 Z9 19 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 IS 19 BP 5264 EP 5274 DI 10.1158/1078-0432.CCR-13-0615 PG 11 WC Oncology SC Oncology GA 228RA UT WOS:000325203700002 PM 24089439 ER PT J AU Sullivan, RJ LoRusso, PM Flaherty, KT AF Sullivan, Ryan J. LoRusso, Patricia M. Flaherty, Keith T. TI The Intersection of Immune-Directed and Molecularly Targeted Therapy in Advanced Melanoma: Where We Have Been, Are, and Will Be SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2 THERAPY; INHIBITOR AZD6244 ARRY-142886; COOPERATIVE-ONCOLOGY-GROUP; PHASE-III TRIAL; T-CELL TRANSFER; METASTATIC MELANOMA; CUTANEOUS MELANOMA; BRAF INHIBITION; MEK INHIBITION AB In three years, four drugs have gained regulatory approval for the treatment of metastatic and unresectable melanoma, with at least seven other drugs having recently completed, currently in, or soon to be in phase III clinical testing. This amazing achievement has been made following a remarkable increase of knowledge in molecular biology and immunology that led to the identification of high-valued therapeutic targets and the clinical development of agents that effectively engage and inhibit these targets. The discovery of either effective molecularly targeted therapies or immunotherapies would have led to dramatic improvements to the standard-of-care treatment of melanoma. However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP-ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. This overview presents the historical context to this therapeutic revolution, reviews the benefits and limitations of current therapies, and provides a look ahead at where the field is headed. (C) 2013 AACR. C1 [Sullivan, Ryan J.; Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [LoRusso, Patricia M.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM kflaherty@partners.org FU NCI NIH HHS [U54 CA163125] NR 113 TC 31 Z9 31 U1 1 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 IS 19 BP 5283 EP 5291 DI 10.1158/1078-0432.CCR-13-2151 PG 9 WC Oncology SC Oncology GA 228RA UT WOS:000325203700005 PM 24089441 ER PT J AU Ott, PA Hodi, FS Robert, C AF Ott, Patrick A. Hodi, F. Stephen Robert, Caroline TI CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; REGULATORY T-CELLS; IMMUNOSTIMULATORY MONOCLONAL-ANTIBODIES; PRETREATED ADVANCED MELANOMA; MEK INHIBITOR TRAMETINIB; DOSE-ESCALATION TRIAL; METASTATIC MELANOMA; CANCER-IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; IMPROVED SURVIVAL AB Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory immune receptors CTLA-4, PD-1, and PD-L1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is the first agent associated with a documented improved overall survival benefit in this patient population. A striking attribute of CTLA-4 blockade is the durability of objective responses, leading to speculation of a possible cure for some patients. Many tumor responses achieved with PD-1 and PD-L1 inhibition were durable in the phase I trials and were seen in a higher proportion of patients with melanoma than typically observed with ipilimumab. Biomarker development to identify the subset of patients with melanoma who will achieve durable clinical benefit with checkpoint blockade is critical; tumor PD-L1 expression has been promising in early studies. The contrast between unprecedented response rates but limited durability of responses achieved with BRAF and MEK inhibition in BRAF(V600)-mutated melanoma and the impressive durability but relatively low rate of response achieved with immune checkpoint blockade is striking. Preclinical data on potential synergies between CTLA-4/PD-1/PD-L1 inhibition and MAPK-targeted therapy is emerging, and combined immune checkpoint blockade and MAPK inhibition are being explored in clinical trials. Other promising approaches to increase the number of patients with melanoma who benefit from durable responses with immune checkpoint blockade include concurrent or sequenced CTLA-4 and PD-1/PD-L1 inhibition and combination with other immunotherapeutic strategies. (C) 2013 AACR. C1 [Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ott, Patrick A.; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Robert, Caroline] Inst Gustave Roussy, Villejuif, France. RP Robert, C (reprint author), Inst Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif, France. EM caroline.robert@gustaveroussy.fr FU Bristol-Myers Squibb; Merck; Roche FX F.S. Hodi has received commercial research support from Bristol-Myers Squibb, Merck, and Roche and is a consultant/advisory board member for Bristol-Myers Squibb and Roche. C. Robert is a consultant/advisory board member for Bristol-Myers Squibb, Merck, GlaxoSmithKline, Roche, and Novartis. No potential conflicts of interest were disclosed by the other author. NR 89 TC 171 Z9 179 U1 8 U2 61 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 IS 19 BP 5300 EP 5309 DI 10.1158/1078-0432.CCR-13-0143 PG 10 WC Oncology SC Oncology GA 228RA UT WOS:000325203700007 PM 24089443 ER PT J AU Rexer, BN Ghosh, R Narasanna, A Estrada, MV Chakrabarty, A Song, Y Engelman, JA Arteaga, CL AF Rexer, Brent N. Ghosh, Ritwik Narasanna, Archana Estrada, Monica Valeria Chakrabarty, Anindita Song, Youngchul Engelman, Jeffrey A. Arteaga, Carlos L. TI Human Breast Cancer Cells Harboring a Gatekeeper T798M Mutation in HER2 Overexpress EGFR Ligands and Are Sensitive to Dual Inhibition of EGFR and HER2 SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; ERBB2 KINASE DOMAIN; TYROSINE KINASE; ACQUIRED-RESISTANCE; LUNG ADENOCARCINOMAS; MAMMARY TUMORIGENESIS; SOMATIC MUTATIONS; UP-REGULATION; IN-VITRO; BCR-ABL AB Purpose: Mutations in receptor tyrosine kinase (RTK) genes can confer resistance to receptor-targeted therapies. A T798M mutation in the HER2 oncogene has been shown to confer resistance to the tyrosine kinase inhibitor (TKI) lapatinib. We studied the mechanisms of HER2-T798M-induced resistance to identify potential strategies to overcome that resistance. Experimental Design: HER2-T798M was stably expressed in BT474 and MCF10A cells. Mutant cells and xenografts were evaluated for effects of the mutation on proliferation, signaling, and tumor growth after treatment with combinations of inhibitors targeting the EGFR/HER2/HER3/PI3K axis. Results: A low 3% allelic frequency of the T798M mutant shifted 10-fold the IC50 of lapatinib. In mutant-expressing cells, lapatinib did not block basal phosphorylation of HER2, HER3, AKT, and ERK1/2. In vitro kinase assays showed increased autocatalytic activity of HER2-T798M. HER3 association with PI3K p85 was increased in mutant-expressing cells. BT474-T798M cells were also resistant to the HER2 antibody trastuzumab. These cells were sensitive to the pan-PI3K inhibitors BKM120 and XL147 and the irreversible HER2/EGFR TKI afatinib but not the MEK1/2 inhibitor CI-1040, suggesting continued dependence of the mutant cells on ErbB receptors and downstream PI3K signaling. BT474-T798M cells showed increased expression of the EGFR ligands EGF, TGF alpha, amphiregulin, and HB-EGF. Addition of the EGFR neutralizing antibody cetuximab or lapatinib restored trastuzumab sensitivity of BT474-T798M cells and xenografts, suggesting that increased EGFR ligand production was causally associated with drug resistance. Conclusions: Simultaneous blockade of HER2 and EGFR should be an effective treatment strategy against HER2 gene-amplified breast cancer cells harboring T798M mutant alleles. (C) 2013 AACR. C1 [Rexer, Brent N.; Ghosh, Ritwik; Narasanna, Archana; Arteaga, Carlos L.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37235 USA. [Chakrabarty, Anindita; Arteaga, Carlos L.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Canc Biol, Nashville, TN 37235 USA. [Estrada, Monica Valeria; Arteaga, Carlos L.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Breast Canc Res Program, Nashville, TN 37235 USA. [Song, Youngchul; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Arteaga, CL (reprint author), VUMC, Div Hematol Oncol, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu FU R01 grant [CA80195]; ACS Clinical Research Professorship Grant [CRP-07-234]; Lee Jeans Translational Breast Cancer Research Program, Breast Cancer Specialized Program of Research Excellence (SPORE) [P50 CA98131]; Vanderbilt-Ingram Cancer Center Support Grant [P30 CA68485]; Susan G. Komen for the Cure Foundation [SAC100013]; DOD Breast Cancer Research Program post-doctoral award [W81XWH-09-1-0474, BC087465]; NCI [K08 CA143153] FX This work was supported by the following: R01 grant CA80195 (to C. L. Arteaga); ACS Clinical Research Professorship Grant CRP-07-234, The Lee Jeans Translational Breast Cancer Research Program, Breast Cancer Specialized Program of Research Excellence (SPORE) P50 CA98131, Vanderbilt-Ingram Cancer Center Support Grant P30 CA68485, Susan G. Komen for the Cure Foundation Grant SAC100013; DOD Breast Cancer Research Program post-doctoral award W81XWH-09-1-0474 (to R. Ghosh); and DOD Breast Cancer Research Program post-doctoral award BC087465, and NCI K08 CA143153 (to B.N. Rexer). NR 53 TC 18 Z9 18 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 IS 19 BP 5390 EP 5401 DI 10.1158/1078-0432.CCR-13-1038 PG 12 WC Oncology SC Oncology GA 228RA UT WOS:000325203700016 PM 23948973 ER PT J AU Ang, JE Gourley, C Powell, CB High, H Shapira-Frommer, R Castonguay, V De Greve, J Atkinson, T Yap, TA Sandhu, S Banerjee, S Chen, LM Friedlander, ML Kaufman, B Oza, AM Matulonis, U Barber, LJ Kozarewa, I Fenwick, K Assiotis, I Campbell, J Chen, L de Bono, JS Gore, ME Lord, CJ Ashworth, A Kaye, SB AF Ang, Joo Ern Gourley, Charlie Powell, C. Bethan High, Hilda Shapira-Frommer, Ronnie Castonguay, Vincent De Greve, Jacques Atkinson, Tina Yap, Timothy A. Sandhu, Shahneen Banerjee, Susana Chen, Lee-May Friedlander, Michael L. Kaufman, Bella Oza, Amit M. Matulonis, Ursula Barber, Louise J. Kozarewa, Iwanka Fenwick, Kerry Assiotis, Ioannis Campbell, James Chen, Lina de Bono, Johann S. Gore, Martin E. Lord, Christopher J. Ashworth, Alan Kaye, Stan B. TI Efficacy of Chemotherapy in BRCA1/2 Mutation Carrier Ovarian Cancer in the Setting of PARP Inhibitor Resistance: A Multi-Institutional Study SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-SEQUENCING DATA; POLY(ADP-RIBOSE) POLYMERASE; SOMATIC MUTATIONS; SOLID TUMORS; OPEN-LABEL; CARCINOMAS; OLAPARIB; THERAPY; MULTICENTER; GUIDELINES AB Purpose: Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated. Experimental Design: We conducted a retrospective review of PBMCOC who received chemotherapy following disease progression on olaparib, administered at >= 200 mg twice daily for one month or more. Tumor samples were obtained in the post-olaparib setting where feasible and analyzed by massively parallel sequencing. Results: Data were collected from 89 patients who received a median of 3 (range 1-11) lines of pre-olaparib chemotherapy. The overall objective response rate (ORR) to post-olaparib chemotherapy was 36% (24 of 67 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) and 45%(35 of 78) by RECIST and/or Gynecologic Cancer InterGroup (GCIG) CA125 criteria with median progression-free survival (PFS) and overall survival (OS) of 17 weeks [95% confidence interval (CI), 13-21] and 34 weeks (95% CI, 26-42), respectively. For patients receiving platinum-based chemotherapy, ORRs were 40% (19 of 48) and 49% (26/53), respectively, with a median PFS of 22 weeks (95% CI, 15-29) and OS of 45 weeks (95% CI, 15-75). An increased platinum-to-platinum interval was associated with an increased OS and likelihood of response following post-olaparib platinum. No evidence of secondary BRCA1/2 mutation was detected in tumor samples of six PARPi-resistant patients [estimated frequency of such mutations adjusted for sample size: 0.125 (95%-CI: 0-0.375)]. Conclusions: Heavily pretreated PBMCOC who are PARPi-resistant retain the potential to respond to subsequent chemotherapy, including platinum-based agents. These data support the further development of PARPi in PBMCOC. (C) 2013 AACR. C1 [Ang, Joo Ern; Yap, Timothy A.; Sandhu, Shahneen; Banerjee, Susana; de Bono, Johann S.; Gore, Martin E.; Kaye, Stan B.] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. [Ang, Joo Ern; Yap, Timothy A.; Sandhu, Shahneen; Banerjee, Susana; de Bono, Johann S.; Gore, Martin E.; Kaye, Stan B.] Inst Canc Res, Sutton SM2 5PT, Surrey, England. [Gourley, Charlie] Univ Edinburgh, Western Gen Hosp, MRC, Edinburgh Canc Res UK Ctr,Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Kozarewa, Iwanka; Fenwick, Kerry; Assiotis, Ioannis; Campbell, James; Chen, Lina] Inst Canc Res, Tumour Profiling Unit, London SW3 6JB, England. [Powell, C. Bethan; Chen, Lee-May] Univ Calif San Francisco, San Francisco, CA 94143 USA. [High, Hilda; Friedlander, Michael L.] Prince Wales Hosp, Prince Wales Clin Sch, Dept Med Oncol, Sydney, NSW, Australia. [Shapira-Frommer, Ronnie; Kaufman, Bella] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Castonguay, Vincent; Oza, Amit M.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [De Greve, Jacques] Vrije Univ Brussel, Ctr Oncol, Brussels, Belgium. [Atkinson, Tina; Matulonis, Ursula] Dana Farber Canc Ctr, Boston, MA USA. RP Kaye, SB (reprint author), Royal Marsden NHS Fdn Trust, Downs Rd,15 Cotswold Rd, Sutton SM2 5PT, Surrey, England. EM stan.kaye@rmh.nhs.uk RI De Greve, Jacques/J-4939-2012; Lord, Christopher/B-3295-2012; OI De Greve, Jacques/0000-0002-2389-0742; Lord, Christopher/0000-0002-3226-0515; Campbell, James/0000-0001-6756-8766 FU AstraZeneca; Cancer Research UK; Experimental Cancer Medicine Centre grants; Wellcome Trust [090952/Z/09/Z]; Scottish Senior Clinical Fellowship Award; National Institute for Health Research Biomedical Research Centre FX Presented herein are follow-up data from patients who previously completed AstraZeneca-sponsored studies (ClinicalTrials.gov: NCT00516373, NCT00777582, NCT00628251, NCT00494442, and NCT00679783). The Drug Development Unit of The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, and Drs. C.J. Lord and A. Ashworth are supported in part by program grants from Cancer Research UK. Support was also provided by Experimental Cancer Medicine Centre grants (to The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, and the Edinburgh Cancer Research UK Centre), the National Institute for Health Research Biomedical Research Centre (jointly to The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research), the Wellcome Trust (grant 090952/Z/09/Z; to J.E. Ang). C. Gourley is supported by a Scottish Senior Clinical Fellowship Award. NR 31 TC 35 Z9 36 U1 0 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 IS 19 BP 5485 EP 5493 DI 10.1158/1078-0432.CCR-13-1262 PG 9 WC Oncology SC Oncology GA 228RA UT WOS:000325203700025 PM 23922302 ER PT J AU Gucalp, A Tolaney, S Isakoff, SJ Ingle, JN Liu, MC Carey, LA Blackwell, K Rugo, H Nabell, L Forero, A Stearns, V Doane, AS Danso, M Moynahan, ME Momen, LF Gonzalez, JM Akhtar, A Giri, DD Patil, S Feigin, KN Hudis, CA Traina, TA AF Gucalp, Ayca Tolaney, Sara Isakoff, Steven J. Ingle, James N. Liu, Minetta C. Carey, Lisa A. Blackwell, Kimberly Rugo, Hope Nabell, Lisle Forero, Andres Stearns, Vered Doane, Ashley S. Danso, Michael Moynahan, Mary Ellen Momen, Lamia F. Gonzalez, Joseph M. Akhtar, Arooj Giri, Dilip D. Patil, Sujata Feigin, Kimberly N. Hudis, Clifford A. Traina, Tiffany A. CA Translational Breast Canc Res TI Phase II Trial of Bicalutamide in Patients with Androgen Receptor-Positive, Estrogen Receptor-Negative Metastatic Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPRESSION; FLUTAMIDE; OUTCOMES; IDENTIFICATION; RECURRENCE; PHENOTYPE; HIRSUTISM; CETUXIMAB; WOMEN AB Purpose: Patients with hormone receptor-negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer. Experimental Design: Tumors from patients with ER/PgR-negative advanced breast cancer were tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining considered positive]. If either the primary or a metastatic site was positive, patients were eligible to receive the AR antagonist bicalutamide at a dose of 150 mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the total number of patients who show a complete response (CR), partial response (PR), or stable disease (SD) > 6 months; secondary endpoints included progression-free survival (PFS) and toxicity. Correlative studies included measurement of circulating endocrine markers and IHC surrogates for basal-like breast cancer. Results: Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR-positive. The 6-month CBR was 19%[95% confidence interval (CI), 7%-39%] for bicalutamide. The median PFS was 12 weeks (95% CI, 11-22 weeks). Bicalutamide was well-tolerated with no grade 4/5 treatment-related adverse events observed. Conclusion: AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer. (C) 2013 AACR. C1 [Gucalp, Ayca; Doane, Ashley S.; Danso, Michael; Moynahan, Mary Ellen; Momen, Lamia F.; Gonzalez, Joseph M.; Akhtar, Arooj; Hudis, Clifford A.; Traina, Tiffany A.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10065 USA. [Giri, Dilip D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Patil, Sujata] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10065 USA. [Feigin, Kimberly N.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Gucalp, Ayca; Hudis, Clifford A.; Traina, Tiffany A.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Tolaney, Sara] Dana Farber Canc Inst, Boston, MA 02115 USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Liu, Minetta C.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Carey, Lisa A.] Univ N Carolina, Chapel Hill, NC USA. [Blackwell, Kimberly] Duke Univ, Med Ctr, Durham, NC USA. [Rugo, Hope] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Nabell, Lisle; Forero, Andres] Univ Alabama Birmingham, Birmingham, AL USA. [Stearns, Vered] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Traina, TA (reprint author), Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, 300 East 66th St, New York, NY 10065 USA. EM trainat@mskcc.org RI Doane, Ashley Stephen/B-7027-2008; Doane, Ashley Stephen/A-6442-2015; OI Doane, Ashley Stephen/0000-0002-1489-1786; Doane, Ashley Stephen/0000-0002-1489-1786; Feigin, Kimberly/0000-0003-1400-6385; Moynahan, Mary Ellen/0000-0002-0167-1020 FU Translational Breast Cancer Research Consortium; Breast Cancer Alliance; AstraZeneca FX This trial was supported in part by the Translational Breast Cancer Research Consortium, Breast Cancer Alliance, and AstraZeneca. NR 35 TC 120 Z9 129 U1 2 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 IS 19 BP 5505 EP 5512 DI 10.1158/1078-0432.CCR-12-3327 PG 8 WC Oncology SC Oncology GA 228RA UT WOS:000325203700027 PM 23965901 ER PT J AU Borrero, S Farkas, A Dehlendorf, C Rocca, CH AF Borrero, Sonya Farkas, Amy Dehlendorf, Christine Rocca, Corinne H. TI Racial and ethnic differences in men's knowledge and attitudes about contraception SO CONTRACEPTION LA English DT Article DE Race; Disparities; Men; Contraception; Attitudes; Knowledge ID DECISION-MAKING; UNITED-STATES; UNINTENDED PREGNANCY; YOUNG-ADULTS; DISPARITIES; WOMEN AB Background: Little is known about racial/ethnic differences in men's contraceptive knowledge and attitudes. Study Design: We used multivariable logistic regression to examine racial/ethnic differences in contraceptive knowledge and attitudes among 903 men aged 18-29 in the 2009 National Survey of Reproductive and Contraceptive Knowledge. Results: Black and Hispanic men were less likely than Whites to have heard of most contraceptive methods, including female and male sterilization, and also had lower knowledge about hormonal and long-acting reversible methods. They were less likely to know that pills are ineffective when 2-3 pills are missed [Blacks: adjusted odds ratio (aOR)=0.42; Hispanics: aOR=0.53] and that fertility was not delayed after stopping the pill (Blacks: aOR=0.52; Hispanics: aOR=0.27). Hispanics were less likely to know that nulliparous women can use the intrauterine device (aOR=0.47). Condom knowledge was similar by race/ethnicity, but Blacks were less likely to view condoms as a hassle than Whites (aOR=0.46). Conclusions: Efforts to educate men, especially men of color, about contraceptive methods are needed. Published by Elsevier Inc. C1 [Borrero, Sonya] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Farkas, Amy] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Dehlendorf, Christine; Rocca, Corinne H.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Bixby Ctr Global Reprod Hlth, San Francisco, CA 94143 USA. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu FU Eunice Kennedy Shriver National Institute of Child Health & Human Development [1R21HD068736-01A1, K23HD067197]; National Campaign to Prevent Teenage and Unplanned Pregnancy [1R21HD068736-01A1, K23HD067197] FX This work was supported by grant numbers 1R21HD068736-01A1 and K23HD067197 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the National Campaign to Prevent Teenage and Unplanned Pregnancy. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the National Institutes of Health. NR 32 TC 6 Z9 6 U1 5 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD OCT PY 2013 VL 88 IS 4 BP 532 EP 538 DI 10.1016/j.contraception.2013.04.002 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 225PN UT WOS:000324974900011 PM 23697702 ER PT J AU Bramoweth, AD Germain, A AF Bramoweth, Adam D. Germain, Anne TI Deployment-Related Insomnia in Military Personnel and Veterans SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Insomnia; Comorbid insomnia; Military personnel; Veterans; PTSD; Depression; Anxiety; Traumatic brain injury; Suicide; Psychotherapy; Pharmacotherapy; Sleep disorders; Psychiatry ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; BRIEF BEHAVIORAL TREATMENT; ADVERSE CHILDHOOD EXPERIENCES; SLEEP DISTURBANCES; COMBAT VETERANS; CHRONIC NIGHTMARES; SERVICE MEMBERS; DEPRESSION; IRAQ AB Insomnia is a prevalent disorder that greatly impacts military personnel, especially those deployed in support of combat efforts. Deployment-related stressors like combat exposure, mild traumatic brain injury (mTBI) irregular sleep-wake schedules, and adjustment to the return home all contribute to insomnia. However, insomnia can also exacerbate the deployment experience and is a risk factor for traumatic stress reactions such as PTSD, depression, and suicide. Military personnel with mTBI are significantly impacted by insomnia; the majority experience sleep disruption and this can impede recovery and rehabilitation. As more service members return home from deployment, treatment is vital to reduce the impact of insomnia. Preliminary outcome data, showing positive results for reduction of sleep disruption, has been found with treatments such as combined cognitive behavioral treatment of insomnia (CBTI) and imagery rehearsal therapy (IRT), preference-based interventions, as well as efforts to broadly disseminate CBTI. The recent literature on the impact and treatment of deployment-related insomnia is reviewed. C1 [Bramoweth, Adam D.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15206 USA. [Bramoweth, Adam D.; Germain, Anne] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Germain, Anne] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Germain, A (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 3811 OHara St,Sterling Plaza 239, Pittsburgh, PA 15213 USA. EM adam.bramoweth@va.gov; germax@upmc.edu OI Bramoweth, Adam/0000-0002-3535-0292 FU VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System; Congressionally Directed Medical Research Program [PT073961 W81XWH-08-1-0637, PR054093-W81XWH-07-PTSD-IIRA]; National Institute of Mental Health [MH080696] FX Dr. Bramoweth's work is supported by resources and funding from the VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC, Director: D. Oslin; Pittsburgh Site Director: G. Haas), VA Pittsburgh Healthcare System. Dr. Germain's work is supported by the Congressionally Directed Medical Research Program (PT073961 W81XWH-08-1-0637; PR054093-W81XWH-07-PTSD-IIRA) and the National Institute of Mental Health (MH080696). The contents do not represent the views of the Department of Veterans Affairs, Department of Defense, or the United States Government. NR 65 TC 12 Z9 13 U1 1 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD OCT PY 2013 VL 15 IS 10 AR 401 DI 10.1007/s11920-013-0401-4 PG 8 WC Psychiatry SC Psychiatry GA 224JI UT WOS:000324880100003 PM 24005883 ER PT J AU Jing, EX O'Neill, BT Rardin, MJ Kleinridders, A Ilkeyeva, OR Ussar, S Bain, JR Lee, KY Verdin, EM Newgard, CB Gibson, BW Kahn, CR AF Jing, Enxuan O'Neill, Brian T. Rardin, Matthew J. Kleinridders, Andre Ilkeyeva, Olga R. Ussar, Siegfried Bain, James R. Lee, Kevin Y. Verdin, Eric M. Newgard, Christopher B. Gibson, Bradford W. Kahn, C. Ronald TI Sirt3 Regulates Metabolic Flexibility of Skeletal Muscle Through Reversible Enzymatic Deacetylation SO DIABETES LA English DT Article ID PYRUVATE-DEHYDROGENASE COMPLEX; LYSINE ACETYLATION; INSULIN-RESISTANCE; CONTRACTILE ACTIVITY; PROTEIN ACETYLATION; GLUCOSE-TRANSPORT; BETA-CELLS; MITOCHONDRIAL; PHOSPHORYLATION; DEFICIENCY AB Sirt3 is an NAD(+)-dependent deacetylase that regulates mitochondrial function by targeting metabolic enzymes and proteins. In fasting mice, Sirt3 expression is decreased in skeletal muscle resulting in increased mitochondrial protein acetylation. Deletion of Sirt3 led to impaired glucose oxidation in muscle, which was associated with decreased pyruvate dehydrogenase (PDH) activity, accumulation of pyruvate and lactate metabolites, and an inability of insulin to suppress fatty acid oxidation. Antibody-based acetyl-peptide enrichment and mass spectrometry of mitochondrial lysates from WT and Sirt3 KO skeletal muscle revealed that a major target of Sirt3 deacetylation is the E1 subunit of PDH (PDH E1). Sirt3 knockout in vivo and Sirt3 knockdown in myoblasts in vitro induced hyperacetylation of the PDH E1 subunit, altering its phosphorylation leading to suppressed PDH enzymatic activity. The inhibition of PDH activity resulting from reduced levels of Sirt3 induces a switch of skeletal muscle substrate utilization from carbohydrate oxidation toward lactate production and fatty acid utilization even in the fed state, contributing to a loss of metabolic flexibility. Thus, Sirt3 plays an important role in skeletal muscle mitochondrial substrate choice and metabolic flexibility in part by regulating PDH function through deacetylation. C1 [Jing, Enxuan; O'Neill, Brian T.; Kleinridders, Andre; Ussar, Siegfried; Lee, Kevin Y.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Rardin, Matthew J.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA USA. [Ilkeyeva, Olga R.; Bain, James R.; Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Verdin, Eric M.] Gladstone Inst Virol & Immunol, San Francisco, CA USA. [Verdin, Eric M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu OI Verdin, Eric/0000-0003-3703-3183; Bain, James/0000-0002-8917-9187; Ussar, Siegfried/0000-0001-7575-0920 FU National Institutes of Health [R24 DK085610]; Joslin Training Grant [T32DK007260]; German Research Foundation [KL2399/1-1]; Human Frontier Science Program Long-Term fellowship; National Center for Research Resources shared instrumentation grant [S10 RR024615] FX The primary funding for this project was National Institutes of Health Grant R24 DK085610. B.T.O. was funded by Joslin Training Grant T32DK007260. A. K. was funded by German Research Foundation project KL2399/1-1. S. U. was supported by a Human Frontier Science Program Long-Term fellowship. The authors acknowledge the support of National Center for Research Resources shared instrumentation grant S10 RR024615 (to B. W. G.) for the QSTAR Elite mass spectrometer used in these studies. NR 51 TC 63 Z9 65 U1 2 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2013 VL 62 IS 10 BP 3404 EP 3417 DI 10.2337/db12-1650 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222RG UT WOS:000324748200024 PM 23835326 ER PT J AU Guo, LL Inada, A Aguayo-Mazzucato, C Hollister-Lock, J Fujitani, Y Weir, GC Wright, CVE Sharma, A Bonner-Weir, S AF Guo, Lili Inada, Akari Aguayo-Mazzucato, Cristina Hollister-Lock, Jennifer Fujitani, Yoshio Weir, Gordon C. Wright, Christopher V. E. Sharma, Arun Bonner-Weir, Susan TI PDX1 in Ducts Is Not Required for Postnatal Formation of beta-Cells but Is Necessary for Their Subsequent Maturation SO DIABETES LA English DT Article ID CARBONIC-ANHYDRASE-II; ENDOCRINE PANCREAS; RAT PANCREAS; ADULT-RATS; EMBRYONIC-DEVELOPMENT; CHRONIC HYPERGLYCEMIA; INSULIN-SECRETION; EXOCRINE PANCREAS; GLUCOSE-TOLERANCE; ISLET NEOGENESIS AB Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of -cell function, was assessed for a possible role in postnatal -cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) mice were euglycemic for the first 2 postnatal weeks but showed moderate hyperglycemia from 3 to 7 weeks of age. By 10 weeks, they had near-normal morning fed glucose levels but showed severely impaired glucose tolerance and insulin secretion. Yet the loss of Pdx1 did not result in decreased islet and -cell mass at 4 and 10 weeks of age. Within the same pancreas, there was a mixed population of islets, with PDX1 and MAFA protein expression normal in some cells and severely diminished in others. Even at 10 weeks, islets expressed immaturity markers. Thus, we conclude that Pdx1 is not necessary for the postnatal formation of -cells but is essential for their full maturation to glucose-responsive -cells. C1 [Guo, Lili; Inada, Akari; Aguayo-Mazzucato, Cristina; Hollister-Lock, Jennifer; Weir, Gordon C.; Sharma, Arun; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Dept Med, Boston, MA 02115 USA. [Inada, Akari] Kyushu Univ, Grad Sch Med Sci, Adv Med Initiat, Fukuoka 812, Japan. [Fujitani, Yoshio; Wright, Christopher V. E.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Dept Med, Boston, MA 02115 USA. EM susan.bonner-weir@joslin.harvard.edu FU National Institutes of Health [R01-DK-44523, P30-DK-36836]; Joslin Diabetes and Endocrinology Research Center (DERC) Advanced Microscopy Core; JDRF [1-2008-45]; Diabetes Research and Wellness Foundation; Daiichi Sankyo Foundation; Ministry of Health, Labor and Welfare of Japan [11103401] FX This study was supported by grants from the National Institutes of Health R01-DK-44523 (S.B.-W.), P30-DK-36836 Joslin Diabetes and Endocrinology Research Center (DERC) Advanced Microscopy Core, and by JDRF 1-2008-45 (S.B.-W.), as well as the Diabetes Research and Wellness Foundation, Daiichi Sankyo Foundation, and a grant from the Ministry of Health, Labor and Welfare of Japan (11103401), and an important group of private donors. No other potential conflicts of interest relevant to this article were reported. NR 58 TC 10 Z9 10 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2013 VL 62 IS 10 BP 3459 EP 3468 DI 10.2337/db12-1833 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222RG UT WOS:000324748200029 PM 23775765 ER PT J AU Yaghootkar, H Lamina, C Scott, RA Dastani, Z Hivert, MF Warren, LL Stancakova, A Buxbaum, SG Lyytikaeinen, LP Henneman, P Wu, Y Cheung, CYY Pankow, JS Jackson, AU Gustafsson, S Zhao, JH Ballantyne, CM Xie, WJ Bergman, RN Boehnke, M el Bouazzaoui, F Collins, FS Dunn, SH Dupuis, J Forouhi, NG Gillson, C Hattersley, AT Hong, JY Kaehoenen, M Kuusisto, J Kedenko, L Kronenberg, F Doria, A Assimes, TL Ferrannini, E Hansen, T Hao, K Haering, H Knowles, JW Lindgren, CM Nolan, JJ Paananen, J Pedersen, O Quertermous, T Smith, U Lehtimaeki, T Liu, CT Loos, RJF McCarthy, MI Morris, AD Vasan, RS Spector, TD Teslovich, TM Tuomilehto, J van Dijk, KW Viikari, JS Zhu, N Langenberg, C Ingelsson, E Semple, RK Sinaiko, AR Palmer, CNA Walker, M Lam, KSL Paulweber, B Mohlke, KL van Duijn, C Raitakari, OT Bidulescu, A Wareham, NJ Laakso, M Waterworth, DM Lawlor, DA Meigs, JB Richards, JB Frayling, TM AF Yaghootkar, Hanieh Lamina, Claudia Scott, Robert A. Dastani, Zari Hivert, Marie-France Warren, Liling L. Stancakova, Alena Buxbaum, Sarah G. Lyytikaeinen, Leo-Pekka Henneman, Peter Wu, Ying Cheung, Chloe Y. Y. Pankow, James S. Jackson, Anne U. Gustafsson, Stefan Zhao, Jing Hua Ballantyne, Christie M. Xie, Weijia Bergman, Richard N. Boehnke, Michael el Bouazzaoui, Fatiha Collins, Francis S. Dunn, Sandra H. Dupuis, Josee Forouhi, Nita G. Gillson, Christopher Hattersley, Andrew T. Hong, Jaeyoung Kaehoenen, Mika Kuusisto, Johanna Kedenko, Lyudmyla Kronenberg, Florian Doria, Alessandro Assimes, Themistocles L. Ferrannini, Ele Hansen, Torben Hao, Ke Haering, Hans Knowles, Joshua W. Lindgren, Cecilia M. Nolan, John J. Paananen, Jussi Pedersen, Oluf Quertermous, Thomas Smith, Ulf Lehtimaeki, Terho Liu, Ching-Ti Loos, Ruth J. F. McCarthy, Mark I. Morris, Andrew D. Vasan, Ramachandran S. Spector, Tim D. Teslovich, Tanya M. Tuomilehto, Jaakko van Dijk, Ko Willems Viikari, Jorma S. Zhu, Na Langenberg, Claudia Ingelsson, Erik Semple, Robert K. Sinaiko, Alan R. Palmer, Colin N. A. Walker, Mark Lam, Karen S. L. Paulweber, Bernhard Mohlke, Karen L. van Duijn, Cornelia Raitakari, Olli T. Bidulescu, Aurelian Wareham, Nick J. Laakso, Markku Waterworth, Dawn M. Lawlor, Debbie A. Meigs, James B. Richards, J. Brent Frayling, Timothy M. CA GENESIS Consortium RISC Consortium TI Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes SO DIABETES LA English DT Article ID MOLECULAR-WEIGHT ADIPONECTIN; GREATER-THAN-G; PLASMA ADIPONECTIN; ADIPOSE-TISSUE; ASSOCIATION ANALYSES; METABOLIC PROFILE; GENETIC-VARIANTS; SUPPRESSION TEST; GLYCEMIC TRAITS; OBESE WOMEN AB Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes. C1 [Yaghootkar, Hanieh; Xie, Weijia; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Sch Med, Exeter, Devon, England. [Lamina, Claudia; Kronenberg, Florian] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria. [Scott, Robert A.; Zhao, Jing Hua; Forouhi, Nita G.; Gillson, Christopher; Loos, Ruth J. F.; Langenberg, Claudia; Wareham, Nick J.] Inst Met Sci, MRC Epidemiol Unit, Cambridge, England. [Dastani, Zari] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3T 1E2, Canada. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Warren, Liling L.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Stancakova, Alena; Kuusisto, Johanna; Hao, Ke; Paananen, Jussi; Laakso, Markku] Univ Eastern Finland, Kuopio, Finland. [Buxbaum, Sarah G.] Jackson State Univ, Sch Hlth Sci, Jackson, MS USA. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland. [Henneman, Peter; el Bouazzaoui, Fatiha; van Dijk, Ko Willems] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Cheung, Chloe Y. Y.; Lam, Karen S. L.] Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Pankow, James S.; Zhu, Na] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Jackson, Anne U.; Boehnke, Michael; Teslovich, Tanya M.] Univ Michigan, Dept Biostat & Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX USA. [Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabetes & Obes Res Inst, Los Angeles, CA 90048 USA. [Collins, Francis S.] Natl Inst Hlth, Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. [Dunn, Sandra H.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Dupuis, Josee; Hong, Jaeyoung; Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Psychol, Tampere, Finland. [Kaehoenen, Mika] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Kedenko, Lyudmyla; Paulweber, Bernhard] Paracelsus Private Med Univ Salzburg, St Johann Spital, Dept Internal Med 1, Salzburg, Austria. [Doria, Alessandro] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Sch Med, Cardiovasc Inst, Stanford, CA 94305 USA. Univ Pisa, Dept Internal Med, Pisa, Italy. [Haering, Hans; Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Nephrol Vasc Med & Clin C, Tubingen, Germany. [Ferrannini, Ele; Lindgren, Cecilia M.; McCarthy, Mark I.; Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Hansen, Torben; Nolan, John J.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Haering, Hans] Hagedorn Res Inst, Copenhagen, Denmark. [Haering, Hans] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark. [Haering, Hans] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Smith, Ulf] Sahlgrens Acad, Lundberg Lab Diabet Res, Dept Mol & Clin Med, Gothenburg, Sweden. [Loos, Ruth J. F.] Inst Child Hlth & Dev, Charles Bronfman Inst Personalized Med, Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford OX3 7LJ, England. [Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Spector, Tim D.; Richards, J. Brent] Kings Coll London, Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabetes Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Viikari, Jorma S.] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland. [Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland. [Semple, Robert K.] Natl Inst Hlth Res Cambridge Biomed Res Ctr, Cambridge, England. [Semple, Robert K.] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Cambridge, England. [Sinaiko, Alan R.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Walker, Mark] Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Lam, Karen S. L.] Univ Hong Kong, Li Ka Shing Fac Med, Res Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Hong Kong, Peoples R China. [van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Bidulescu, Aurelian] Inst Cardiovasc Res, Morehouse Sch Med, Atlanta, GA USA. [Bidulescu, Aurelian] Morehouse Sch Med, Dept Community Hlth & Prevent Med, Atlanta, GA 30310 USA. [Waterworth, Dawn M.] GlaxoSmithKline, Upper Merion, PA USA. [Lawlor, Debbie A.] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Richards, J. Brent] McGill Univ, Dept Med Human Genet Epidemiol & Biostat, Montreal, PQ, Canada. RP Frayling, TM (reprint author), Univ Exeter, Sch Med, Exeter, Devon, England. EM tim.frayling@pms.ac.uk RI Colaus, PsyColaus/K-6607-2013; Palmer, Colin/C-7053-2008; Willems van Dijk, Ko/A-1798-2008; Bidulescu, Aurelian/N-2617-2014; Kronenberg, Florian/B-1736-2008; Lyytikainen, Leo-Pekka/C-8544-2016; Study, GoDARTS/K-9448-2016; Buxbaum, Sarah/E-1970-2013 OI Forouhi, Nita/0000-0002-5041-248X; Lawlor, Debbie A/0000-0002-6793-2262; Pankow, James/0000-0001-7076-483X; Hattersley, Andrew/0000-0001-5620-473X; Palmer, Colin/0000-0002-6415-6560; Willems van Dijk, Ko/0000-0002-2172-7394; Ramachandran, Vasan/0000-0001-7357-5970; Semple, Robert/0000-0001-6539-3069; Bidulescu, Aurelian/0000-0001-8211-8309; Kronenberg, Florian/0000-0003-2229-1120; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Paananen, Jussi/0000-0001-5100-4907; Buxbaum, Sarah/0000-0002-4886-3564 FU Biotechnology and Biological Sciences Research Council [G20234]; Canadian Institutes of Health Research; Diabetes UK [12/0004470]; FIC NIH HHS [TW05596]; Intramural NIH HHS; Medical Research Council [G0500070, G0600705, MC_U106179471, MC_U106188470, MC_UP_A100_1003, MC_UU_12013/5]; NCATS NIH HHS [UL1 TR000454]; NCRR NIH HHS [MO1-RR-00400, RR20649, UL1 RR025008, UL1RR025005]; NHGRI NIH HHS [U01HG004402, 1Z01 HG000024, N01-HG-65403]; NHLBI NIH HHS [HL085144, HL52851, N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-95170, N01-HC-95171, N01-HC-95172, R01 HL105756, R01HL086694, R01HL087641, R01HL59367, RC2 HL102419, UH1 HL073461]; NIDDK NIH HHS [DK062370, DK072193, DK078150, DK36836-25, DK56350, K24 DK080140, P30 DK020572, R01 DK072193, R01 DK078616, R01 DK093757, R01DK056918]; NIEHS NIH HHS [ES10126]; NIMHD NIH HHS [P20 MD006899]; NINR NIH HHS [T32 NR009759]; Wellcome Trust [, 090532, 098498, 100574] NR 58 TC 42 Z9 42 U1 0 U2 26 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2013 VL 62 IS 10 BP 3589 EP 3598 DI 10.2337/db13-0128 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222RG UT WOS:000324748200043 PM 23835345 ER PT J AU Berkowitz, SA Baggett, TP Wexler, DJ Huskey, KW Wee, CC AF Berkowitz, Seth A. Baggett, Travis P. Wexler, Deborah J. Huskey, Karen W. Wee, Christina C. TI Food Insecurity and Metabolic Control Among US Adults With Diabetes SO DIABETES CARE LA English DT Article ID CHRONIC DISEASE; HEALTH; DISPARITIES; MORTALITY; RISK AB OBJECTIVEWe sought to determine whether food insecurity is associated with worse glycemic, cholesterol, and blood pressure control in adults with diabetes.RESEARCH DESIGN AND METHODSWe conducted a cross-sectional analysis of data from participants of the 1999-2008 National Health and Nutrition Examination Survey. All adults with diabetes (type 1 or type 2) by self-report or diabetes medication use were included. Food insecurity was measured by the Adult Food Security Survey Module. The outcomes of interest were proportion of patients with HbA(1c) >9.0% (75 mmol/mol), LDL cholesterol >100 mg/dL, and systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg. We used multivariable logistic regression for analysis.RESULTSAmong the 2,557 adults with diabetes in our sample, a higher proportion of those with food insecurity (27.0 vs. 13.3%, P < 0.001) had an HbA(1c) >9.0% (75 mmol/mol). After adjustment for age, sex, educational attainment, household income, insurance status and type, smoking status, BMI, duration of diabetes, diabetes medication use and type, and presence of a usual source of care, food insecurity remained significantly associated with poor glycemic control (odds ratio [OR] 1.53 [95% CI 1.07-2.19]). Food insecurity was also associated with poor LDL control before (68.8 vs. 49.8, P = 0.002) and after (1.86 [1.01-3.44]) adjustment. Food insecurity was not associated with blood pressure control.CONCLUSIONSFood insecurity is significantly associated with poor metabolic control in adults with diabetes. Interventions that address food security as well as clinical factors may be needed to successfully manage chronic disease in vulnerable adults. C1 [Berkowitz, Seth A.; Baggett, Travis P.] Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02114 USA. [Berkowitz, Seth A.; Baggett, Travis P.; Wexler, Deborah J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA. [Wexler, Deborah J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Ctr,Dept Med, Boston, MA USA. [Huskey, Karen W.; Wee, Christina C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care,Dept Med, Boston, MA 02215 USA. RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02114 USA. EM saberkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU institutional National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; General Medicine Division at Massachusetts General Hospital; National Institute on Drug Abuse of the National Institutes of Health [K23-DA-034008]; National Institutes of Health [R03-DK-090196, K24-DK-087932] FX S.A.B. was supported by an institutional National Research Service Award (T32HP10251), the Ryoichi Sasakawa Fellowship Fund, and the General Medicine Division at Massachusetts General Hospital. T.P.B. receives funding from the National Institute on Drug Abuse of the National Institutes of Health (K23-DA-034008). D.J.W. receives funding from the National Institutes of Health (R03-DK-090196). C.C.W. is supported by a midcareer mentorship award from the National Institutes of Health (K24-DK-087932). NR 28 TC 25 Z9 25 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2013 VL 36 IS 10 BP 3093 EP 3099 DI 10.2337/dc13-0570 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222RT UT WOS:000324749500047 PM 23757436 ER PT J AU Jacobson, AM Braffett, BH Cleary, PA Gubitosi-Klug, RA Larkin, ME AF Jacobson, Alan M. Braffett, Barbara H. Cleary, Patricia A. Gubitosi-Klug, Rose A. Larkin, Mary E. CA DCCT EDIC Res Grp TI The Long-Term Effects of Type 1 Diabetes Treatment and Complications on Health-Related Quality of Life A 23-year follow-up of the Diabetes Control and Complications/Epidemiology of Diabetes Interventions and Complications cohort SO DIABETES CARE LA English DT Article ID SURVEY SF-36; MACULAR EDEMA; RETINOPATHY; TRIAL; MELLITUS; TRANSPLANTATION; RELIABILITY; MANAGEMENT; VALIDITY; THERAPY AB OBJECTIVETo examine the long-term effects of type 1 diabetes treatment, metabolic control, and complications on health-related quality of life (HRQOL).RESEARCH DESIGN AND METHODSA total of 1,441 participants, initially 13-39 years of age, were followed for an average of 23.5 years as part of the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. The Diabetes Quality-of-Life questionnaire (DQOL) was administered annually during DCCT and every other year during EDIC. Biomedical data, including HbA(1c) levels, exposure to severe hypoglycemia, intercurrent psychiatric events, and development of diabetes complications were collected at regular intervals throughout the follow-up.RESULTSMean total DQOL scores were not significantly different between the former DCCT intensive and conventional treatment groups (DCCT baseline, 78 8 vs. 78 +/- 9; EDIC year 17, 75 +/- 11 vs. 74 +/- 11). Over the course of the study, a drop of 5 points in DQOL score from DCCT baseline maintained on two successive visits occurred in 755 individuals and was associated with increased HbA(1c), albumin excretion rate, mean blood pressure, BMI, and occurrence of hypoglycemic events requiring assistance. Lower DQOL scores after 23.5 years of follow-up were associated with prior development of retinopathy (P = 0.0196), nephropathy (P = 0.0019), and neuropathy (P < 0.0001) as well as self-reported chest pain (P = 0.0004), decreased vision in both eyes (P = 0.0005), painful paresthesias (P < 0.0001), recurrent urinary incontinence (P = 0.0001), erectile dysfunction (P < 0.0001), and history of psychiatric events (P < 0.0001).CONCLUSIONSAmong DCCT/EDIC participants, worsening metabolic control, serious diabetes complications and their associated symptoms, and development of psychiatric conditions led to decreased HRQOL. C1 [Jacobson, Alan M.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Jacobson, Alan M.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Braffett, Barbara H.; Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Gubitosi-Klug, Rose A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Larkin, Mary E.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. RP Jacobson, AM (reprint author), Winthrop Univ Hosp, Mineola, NY 11501 USA. EM amjacobson@winthrop.org RI van der Geest, Rob/J-8193-2015 OI van der Geest, Rob/0000-0002-9084-5597 FU Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, National Eye Institute, National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical and Translational Science Awards Program; National Center for Research Resources; Genentech; National Institute of Diabetes and Digestive and Kidney Diseases; Herbert Graetz Psychosocial Research Fund (Joslin Diabetes Center); Winthrop University Hospital Research Institute FX Abbott, Animas, Aventis, Becton Dickinson, Bayer, Can-Am, Eli Lilly, LifeScan, Medtronic MiniMed, Omron, and Roche contributed free or discounted supplies and/or equipment. The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, National Eye Institute, National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program and the Clinical and Translational Science Awards Program, National Center for Research Resources, and Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. This work is supported in part by funding from the Herbert Graetz Psychosocial Research Fund (Joslin Diabetes Center) and the Winthrop University Hospital Research Institute. No other potential conflicts of interest relevant to this article were reported. NR 35 TC 23 Z9 23 U1 2 U2 18 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2013 VL 36 IS 10 BP 3131 EP 3138 DI 10.2337/dc12-2109 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222RT UT WOS:000324749500053 PM 23835693 ER PT J AU Turek, SJ Hastings, SM Sun, JK King, GL Keenan, HA AF Turek, Sara J. Hastings, Stephanie M. Sun, Jennifer K. King, George L. Keenan, Hillary A. TI Sexual Dysfunction as a Marker of Cardiovascular Disease in Males With 50 or More Years of Type 1 Diabetes SO DIABETES CARE LA English DT Article ID CORONARY-ARTERY-DISEASE; ERECTILE DYSFUNCTION; 50-YEAR MEDALIST; NATURAL-HISTORY; JUVENILE-ONSET; RISK; COMPLICATIONS; MEN; MELLITUS; DURATION AB OBJECTIVEVascular dysfunction is a major contributor to diabetes complications. It is also the primary physiologic cause of erectile dysfunction and considered an independent predictor of cardiovascular disease (CVD) in males over age 40 years. A cohort of individuals with 50 or more years of type 1 diabetes, Joslin Medalists, have low rates of small but not large vessel complications. This study aims to identify the prevalence and longitudinal association of sexual dysfunction (SD) with CVD in Joslin Medalists.RESEARCH DESIGN AND METHODSDescription and association of self-assessment of SD in males of the Medalist cohort by self-reported sexual problems with CVD. SD is validated through the use of the abbreviated International Index of Erectile Dysfunction (IIEF).RESULTSOf 301 males in the Medalist Study, 69.8% reported a history of SD. Unadjusted risk factors included elevated glycated hemoglobin (HbA(1c)) (P = 0.02), elevated BMI (P = 0.03), higher total cholesterol (P = 0.02), lower HDL (P < 0.01), and increased levels of interleukin-6 (P = 0.03). SD was independently associated with CVD (age-, HbA(1c)-, and BMI-adjusted OR 1.9 [95% CI 1.0-3.5]). In adjusted analyses, retinal, neural, and renal complications were not associated (P > 0.05) with SD. Current report of SD (IIEF score 17) in a subset of Medalists was significantly correlated with self-reported longitudinal SD.CONCLUSIONSSD in those with extreme-duration type 1 diabetes is independently associated with CVD, representing a large-vessel pattern. The findings suggest that SD may predict CVD in those with type 1 diabetes of long duration. These individuals have also been found to be relatively free of microvascular complications. C1 [Turek, Sara J.; Hastings, Stephanie M.; Sun, Jennifer K.; King, George L.; Keenan, Hillary A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Sun, Jennifer K.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [King, George L.; Keenan, Hillary A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Keenan, HA (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM hillary.keenan@joslin.harvard.edu FU Juvenile Diabetes Research Foundation [8-2005-358, nPOD 25-2008-383, 18-2008-363]; Beatson Foundation; Brehm Foundation; National Institutes of Health [1R24-DK-090961-01, DP3-DK-094333-01]; Peabody Foundation FX This research was funded by the Juvenile Diabetes Research Foundation (8-2005-358, nPOD 25-2008-383, and 18-2008-363), the Beatson Foundation, the Brehm Foundation, the National Institutes of Health (1R24-DK-090961-01 and DP3-DK-094333-01), and the Peabody Foundation. NR 33 TC 4 Z9 5 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2013 VL 36 IS 10 BP 3222 EP 3226 DI 10.2337/dc13-0294 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 222RT UT WOS:000324749500065 PM 23780949 ER PT J AU Chamberland, JP Berman, RL Aronis, KN Mantzoros, CS AF Chamberland, John P. Berman, Reena L. Aronis, Konstantinos N. Mantzoros, Christos S. TI Chemerin is expressed mainly in pancreas and liver, is regulated by energy deprivation, and lacks day/night variation in humans SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HYPOTHALAMIC AMENORRHEA; LEPTIN CONCENTRATIONS; GLUCOSE-HOMEOSTASIS; METABOLIC SYNDROME; RECEPTOR CHEMR23; HUMAN PHYSIOLOGY; FACTOR-ALPHA; HEALTHY-MEN; WEIGHT-LOSS AB Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin's function and expression, its physiology and expression patterns are still to be elucidated in humans. Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether energy deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose-effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion. Results: Chemerin does not display a day/night variation, while acute energy deprivation resulted in a significant drop in circulating chemerin levels by similar to 42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen. Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice. C1 [Chamberland, John P.; Berman, Reena L.; Aronis, Konstantinos N.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Chamberland, John P.; Berman, Reena L.; Aronis, Konstantinos N.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Aronis, Konstantinos N.; Mantzoros, Christos S.] Boston Univ, Boston Med Ctr, Dept Med, Boston, MA 02118 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Cambridge, MA 02138 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; OI Aronis, Konstantinos/0000-0001-7189-8434; Chamberland, John/0000-0002-7862-1371 FU Harvard Clinical and Translational Science Center, from the National Center for Research Resources [UL1 RR025758]; National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX The project described was supported by grant number UL1 RR025758 - Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grants 58785, 79929, and 81913 as well as Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. Amylin Pharmaceuticals, Inc. supplied metreleptin for this study but had no role in the study design, conduct of the study, collection, management, analysis, and interpretation of the data, or the preparation, review, or approval of the manuscript. NR 42 TC 13 Z9 13 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD OCT PY 2013 VL 169 IS 4 BP 453 EP 462 DI 10.1530/EJE-13-0098 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228RD UT WOS:000325204000012 PM 23904282 ER PT J AU Lu, H Zhang, W Graham, DY AF Lu, Hong Zhang, Wei Graham, David Y. TI Bismuth-containing quadruple therapy for Helicobacter pylori: lessons from China SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE Helicobacter pylori; quadruple therapy; review; treatment; treatment success ID TRIPLE THERAPY; ANTIBIOTIC-RESISTANCE; DUODENAL-ULCER; PEPTIC-ULCER; OPEN-LABEL; CURE RATE; IN-VITRO; ERADICATION; EFFICACY; INFECTION AB Antimicrobial resistance has continued to undermine many popular anti-Helicobacter pylori therapies. Antibiotic resistance to commonly used anti-H. pylori drugs in China has increased markedly, making China an ideal site to identify regimens that remain effective despite widespread antimicrobial resistance. Bismuth is one of the few antimicrobials to which resistance does not develop. Factors contributing to H. pylori treatment success include host factors (e.g. genetic differences in the metabolism of the drugs used), bacterial factors (e.g. susceptibility), and details of the regimen (e.g. doses, dosing interval, dosing in relation to meals, formulation, etc.). We reviewed the recent experience in China with bismuth-containing quadruple therapies. The experience consists of 16 studies with 25 arms involving 1971 patients to identify successful regimens (defined as reliably obtaining 90% or greater eradication per protocol) deserving further study. Despite high rates of resistance to commonly used antimicrobials, several regimens could achieve high success. These were characteristically 14-day regimens containing a proton pump inhibitor and either tetracycline and metronidazole or furazolidone and amoxicillin. We propose approaches for further development including for optimization and simplification related to convenience and side effects (e.g. twice rather than three or four times daily or administration at the noon and evening meal instead of at breakfast and evening) while maintaining effectiveness of at least 90%. Studies in China identified regimens that were highly effective despite the high prevalence of resistance to metronidazole, fluoroquinolones, and macrolides. Multicenter randomized studies will be required to confirm which is the best. C1 [Lu, Hong; Zhang, Wei] Shanghai Jiao Tong Univ, Key Lab Gastroenterol & Hepatol, Shanghai Inst Digest Dis, Sch Med,GI Div,Ren Ji Hosp,Minist Hlth, Shanghai 200030, Peoples R China. [Graham, David Y.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-322 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Renji Hospital, Shanghai Jiao-Tong University School of Medicine); National Natural Science Foundation of China [81170355, 81200287]; Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service Grant [DK56338, DK067366, CA116845] FX This study was supported by the grant for Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Renji Hospital, Shanghai Jiao-Tong University School of Medicine), and the National Natural Science Foundation of China (81170355, 81200287). Dr Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service Grant DK56338, which funds the Texas Medical Center Digestive Diseases Center, DK067366 and CA116845. NR 58 TC 20 Z9 23 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD OCT PY 2013 VL 25 IS 10 BP 1134 EP 1140 DI 10.1097/MEG.0b013e3283633b57 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 219SX UT WOS:000324530800002 PM 23778309 ER PT J AU Win, AZ Aparici, CM AF Win, Aung Zaw Aparici, Carina Mari TI Real-time FDG PET/CT-guided bone biopsy in a patient with two primary malignancies SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material C1 [Win, Aung Zaw] San Francisco VA Med Ctr, Nucl Med Sect, Dept Radiol, San Francisco, CA 94121 USA. [Aparici, Carina Mari] Univ Calif San Francisco, Dept Radiol, Nucl Med Sect, San Francisco, CA 94143 USA. RP Win, AZ (reprint author), San Francisco VA Med Ctr, Nucl Med Sect, Dept Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM aungzwin@gmail.com NR 4 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2013 VL 40 IS 11 BP 1787 EP 1788 DI 10.1007/s00259-013-2492-x PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 227QO UT WOS:000325128800017 PM 23828652 ER PT J AU Canavarro, C Teles, RP Capelli, J AF Canavarro, Cristiane Teles, Ricardo Palmier Capelli Junior, Jonas TI Matrix metalloproteinases-1,-2,-3,-7,-8,-12, and-13 in gingival crevicular fluid during orthodontic tooth movement: a longitudinal randomized split-mouth study SO EUROPEAN JOURNAL OF ORTHODONTICS LA English DT Article ID HUMAN PERIODONTAL-LIGAMENT; TISSUE INHIBITORS; IN-VITRO; EXPRESSION; METALLOPROTEINASE-1; FIBROBLASTS; INTERLEUKIN-1-BETA; GENES; ALPHA; BETA AB This randomized split-mouth study aimed to examine the levels of matrix metalloproteinases (MMPs) -1, -2, -3, -7, -8, -12, and -13 in the gingival crevicular fluid (GCF) at different time points during orthodontic tooth movement. A total of 16 healthy orthodontic subjects (7 females, 9 males; mean age, 17.7 years) who needed their first upper premolars extracted were enrolled. One randomly chosen maxillary canine was subjected to a distalizing force and was considered to be the test side. The contralateral canine, which was not subjected to any force but was included in the orthodontic appliance, was used as a control side. GCF sampling was performed at both the mesial (tension) and distal (pressure) test and control sites at baseline, immediately before applying the orthodontic appliance, and after 1 and 24 hours and 7, 14, and 21 days. A multiplexed bead immunoassay was used to analyse the GCF samples. The mean levels of the MMP-1, -2, -3, -7, -8, -12, and -13 were not significantly different between the test and control groups in each time showed. The comparisons between the tension and pressure sites were also not significantly different at each individual time. A few variations focused on MMP-1 and -3, but the expression of MMP-8 was higher than that of the other MMPs. MMPs are released in sufficient quantities such that tooth movement occurs but with no significant increase in GCF levels. C1 [Canavarro, Cristiane; Capelli Junior, Jonas] Univ Estado Rio De Janeiro, Dept Orthodont, Sch Dent, BR-20551030 Rio De Janeiro, RJ, Brazil. [Teles, Ricardo Palmier] Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Canavarro, C (reprint author), Univ Estado Rio De Janeiro, Dept Orthodont, Blvd Vinte & Oito Setembro 157-230, BR-20551030 Rio De Janeiro, RJ, Brazil. EM cristianecanavarro@gmail.com FU FAPERJ (Research Support Foundation of the State of Rio de Janeiro; Brazil) [E-26/111.155/2011] FX The authors would like to thank FAPERJ (Research Support Foundation of the State of Rio de Janeiro; Brazil) for financial support (grant number: E-26/111.155/2011). NR 29 TC 1 Z9 3 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0141-5387 J9 EUR J ORTHODONT JI Eur. J. Orthodont. PD OCT PY 2013 VL 35 IS 5 BP 652 EP 658 DI 10.1093/ejo/cjs053 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 227HQ UT WOS:000325103700016 PM 22989715 ER PT J AU LaVela, SL Gering, J Schectman, G Locatelli, SM Weaver, FM Davies, M AF LaVela, Sherri L. Gering, Jeffrey Schectman, Gordon Locatelli, Sara M. Weaver, Frances M. Davies, Michael TI Improving the quality of telephone-delivered health care: a national quality improvement transformation initiative SO FAMILY PRACTICE LA English DT Article DE Health communication; health care delivery; primary health care; patient preference; patient-centred care; quality improvement ID PATIENT SATISFACTION; CONSULTATION; INFORMATION; CALLERS; VETERAN; ADVICE; ACCESS AB Many Veterans Affairs (VA) primary care (PC) patients prefer telephone-delivered care to other health care delivery modalities. To evaluate PC patients telephone experiences and outcomes before and after a national telephone transformation quality improvement (QI) collaborative. Cross-sectional surveys were conducted pre- and post-collaborative. We used bivariate analyses to assess differences in pre/post outcomes and multivariate regression to identify variables associated with patients perceptions of poor quality care. Patients from 13 VA facilities participated (n 730; pre-intervention 314, post-intervention 416); most of them were males (90%) with a mean age of 62 years. After the collaborative (versus pre-collaborative), few experienced transfers (52% versus 62%, P 0.0006) and most reported timely call answer (88% versus 80%, P 0.003). Improvements in staff understanding why patients were calling and providing needed medical information were also found. There were measurable improvements in patient satisfaction (87% versus 82% very/mostly satisfied, P 0.04) and perceived quality of telephone care (85% versus 78% excellent/good quality, P 0.01) post- collaborative. The proportion of veterans who reported delayed care due to telephone access issues decreased from 41% to 15% after the collaborative, P < 0.0001. Perceptions of poor quality care were higher when calls were for urgent care needs did not result in receipt of needed information and included a transfer or untimely answer. The QI collaborative led to improvements in timeliness of answering calls, patient satisfaction and perceptions of high-quality telephone care and fewer reports of health care delays. Barriers to optimal telephone care quality include untimely answer, transfers, non-receipt of needed information and urgent care needs. C1 [LaVela, Sherri L.; Locatelli, Sara M.; Weaver, Frances M.] US Dept Vet Affairs, Ctr Management Complex Chron Care, Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [LaVela, Sherri L.] Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [Gering, Jeffrey] Chillicothe Vet Affairs Med Ctr, Chillicothe, OH USA. [Gering, Jeffrey] Ohio Univ, Chillicothe, OH USA. [Schectman, Gordon] Vet Affairs Cent Off, Off Patient Care Serv, Washington Dc, CO USA. [Schectman, Gordon] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Program Hlth Serv Res, Maywood, IL 60153 USA. [Davies, Michael] Vet Affairs Cent Off, Off Syst Redesign, Washington Dc, CO USA. RP LaVela, SL (reprint author), US Dept Vet Affairs, Ctr Management Complex Chron Care, 5000 S 5th Ave,151H, Hines, IL 60141 USA. EM Sherri.LaVela@va.gov FU Office of Systems Redesign of the Department of Veterans Affairs FX The authors wish to thank the PC patients who participated in this study. This material is based upon work supported by the Office of Systems Redesign of the Department of Veterans Affairs. This paper reflects only the authors' opinions and does not necessarily reflect the official position of the Department of Veterans Affairs. A portion of these findings were presented as a poster at the VA HSR&D 2012 annual meeting. NR 24 TC 2 Z9 2 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 J9 FAM PRACT JI Fam. Pr. PD OCT PY 2013 VL 30 IS 5 BP 533 EP 540 DI 10.1093/fampra/cmt020 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 228KF UT WOS:000325184200009 PM 23689516 ER PT J AU Mayer, CL Huber, BR Peskind, E AF Mayer, Cynthia L. Huber, Bertrand R. Peskind, Elaine TI Traumatic Brain Injury, Neuroinflammation, and Post-Traumatic Headaches SO HEADACHE LA English DT Review DE traumatic brain injury; inflammation; glia; microglia; astrocytes; satellite cells; blood brain barrier; cytokines; post-traumatic headaches; inflammatory mediators ID CENTRAL-NERVOUS-SYSTEM; SATELLITE GLIAL-CELLS; CORTICAL SPREADING DEPRESSION; DIFFUSE AXONAL INJURY; TUMOR-NECROSIS-FACTOR; CHRONIC PAIN; HEAD-INJURY; INFLAMMATORY RESPONSE; NEUROPATHIC PAIN; CERVICOGENIC HEADACHE AB Concussions following head and/or neck injury are common, and although most people with mild injuries recover uneventfully, a subset of individuals develop persistent post-concussive symptoms that often include headaches. Post-traumatic headaches vary in presentation and may progress to become chronic and in some cases debilitating. Little is known about the pathogenesis of post-traumatic headaches, although shared pathophysiology with that of the brain injury is suspected. Following primary injury to brain tissues, inflammation rapidly ensues; while this inflammatory response initially provides a defensive/reparative function, it can persist beyond its beneficial effect, potentially leading to secondary injuries because of alterations in neuronal excitability, axonal integrity, central processing, and other changes. These changes may account for the neurological symptoms often observed after traumatic brain injury, including headaches. This review considers selected aspects of the inflammatory response following traumatic brain injury, with an emphasis on the role of glial cells as mediators of maladaptive post-traumatic inflammation. C1 [Mayer, Cynthia L.; Huber, Bertrand R.; Peskind, Elaine] VA Puget Sound Hlth Care Syst, VA Northwest Network Mental Illness Res Educ & Cl, Seattle, WA 98108 USA. [Mayer, Cynthia L.; Peskind, Elaine] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Mayer, CL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S116 MIRECC, Seattle, WA 98108 USA. EM cmayer@u.washington.edu FU NIA NIH HHS [P50 AG005136] NR 143 TC 26 Z9 27 U1 0 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD OCT PY 2013 VL 53 IS 9 BP 1523 EP 1530 DI 10.1111/head.12173 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 228AH UT WOS:000325156600020 PM 24090534 ER PT J AU Fung, V Reed, M Price, M Brand, R Dow, WH Newhouse, JP Hsu, J AF Fung, Vicki Reed, Mary Price, Mary Brand, Richard Dow, William H. Newhouse, Joseph P. Hsu, John TI Responses to Medicare Drug Costs among Near-Poor versus Subsidized Beneficiaries SO HEALTH SERVICES RESEARCH LA English DT Article DE Medicare; low-income subsidies; drug cost-sharing ID PART-D; COVERAGE AB ObjectiveThere is limited information on the protective value of Medicare Part D low-income subsidies (LIS). We compared responses to drug costs for LIS recipients with near-poor (200 percent of the Federal Poverty Level) and higher income beneficiaries without the LIS. Data Sources/Study SettingMedicare Advantage beneficiaries in 2008. Study DesignWe examined three drug cost responses using multivariate logistic regression: cost-reducing behaviors (e.g., switching to generics), nonadherence (e.g., not refilling prescriptions), and financial stress (e.g., going without necessities). Data CollectionTelephone interviews in a stratified random sample (N=1,201, 70 percent response rate). Principal FindingsAfter adjustment, a comparable percentage of unsubsidized near-poor (26 percent) and higher income beneficiaries reported cost-reducing behaviors (23 percent, p=.63); fewer LIS beneficiaries reported cost-reducing behaviors (15 percent, p=.019 vs near-poor). Unsubsidized near-poor beneficiaries were more likely to reduce adherence (8.2 percent) than higher income (3.5 percent, p=.049) and LIS beneficiaries (3.1 percent, p=.027). Near-poor beneficiaries also more frequently experienced financial stress due to drug costs (20 percent) than higher income beneficiaries (11 percent, p=.050) and LIS beneficiaries (11 percent, p=.015). ConclusionsLow-income subsidies provide protection from drug cost-related nonadherence and financial stress. Beneficiaries just above the LIS income threshold are most at risk for these potentially adverse behaviors. C1 [Fung, Vicki; Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Reed, Mary; Price, Mary] Kaiser Permanente, Div Res, Oakland, CA USA. [Brand, Richard] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Dow, William H.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Kennedy Sch, Cambridge, MA 02138 USA. [Hsu, John] HMS, Boston, MA USA. RP Fung, V (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor,Suite 901, Boston, MA 02114 USA. EM vfung@partners.org OI Dow, William/0000-0002-4080-1668 FU Kaiser Permanente Community Benefit Program; National Institute on Aging FX The Kaiser Permanente Community Benefit Program and the National Institute on Aging provided the funding for the study. Joseph Newhouse is a director of, and holds equity in, Aetna, which sells Part D plans. NR 21 TC 4 Z9 4 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2013 VL 48 IS 5 BP 1653 EP 1668 DI 10.1111/1475-6773.12062 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 225YF UT WOS:000325000400007 PM 23663197 ER PT J AU Freedman, RA He, YL Winer, EP Keating, NL AF Freedman, Rachel A. He, Yulei Winer, Eric P. Keating, Nancy L. TI Racial/Ethnic Differences in Receipt of Timely Adjuvant Therapy for Older Women with Breast Cancer: Are Delays Influenced by the Hospitals Where Patients Obtain Surgical Care? SO HEALTH SERVICES RESEARCH LA English DT Article DE Breast cancer; delays; disparities ID ACUTE MYOCARDIAL-INFARCTION; SEER-MEDICARE DATA; RACIAL DISPARITIES; COMORBIDITY INDEX; UNITED-STATES; COLON-CANCER; SURGERY; CHEMOTHERAPY; QUALITY; SURVIVAL AB ObjectiveTo examine whether hospitals where patients obtain care explain racial/ethnic differences in treatment delay. Data SourceSurveillance, Epidemiology, and End Results data linked with Medicare claims. Study DesignWe examined delays in adjuvant chemotherapy or radiation for women diagnosed with stage I-III breast cancer during 1992-2007. We used multivariable logistic regression to assess the probability of delay by race/ethnicity and included hospital fixed effects to assess whether hospitals explained disparities. Principal FindingsAmong 54,592 women, black (11.9 percent) and Hispanic (9.9 percent) women had more delays than whites (7.8 percent, p<.0001). After adjustment, black (vs. white) women had higher odds of delay (odds ratio=1.25, 95 percent confidence interval=1.10-1.42), attenuated somewhat by including hospital fixed effects (OR=1.17, 95 percent CI=1.02-1.33). ConclusionsHospitals are the important contributors to racial disparities in treatment delay. C1 [Freedman, Rachel A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Rachel_Freedman@dfci.harvard.edu FU California Department of Public Health as part of the statewide cancer reporting program [103885]; National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136, N01-PC-35139, N02-PC45105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02] FX The authors would like to thank Yang Xu, MS, and Huichuan Lii, MS, MA, for their expert programming assistance. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries m the creation of the SEER-Medicare database. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC45105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. NR 36 TC 12 Z9 12 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2013 VL 48 IS 5 BP 1669 EP 1683 DI 10.1111/1475-6773.12063 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 225YF UT WOS:000325000400008 PM 23663229 ER PT J AU Liu, CF Burgess, JF Manning, WG Maciejewski, ML AF Liu, Chuan-Fen Burgess, James F., Jr. Manning, Willard G. Maciejewski, Matthew L. TI Beta-Binomial Regression and Bimodal Utilization SO HEALTH SERVICES RESEARCH LA English DT Article DE Beta-binomial; bimodal; veterans; primary care; Medicare; utilization AB ObjectiveTo illustrate how the analysis of bimodal U-shaped distributed utilization can be modeled with beta-binomial regression, which is rarely used in health services research. Data Sources/Study SettingVeterans Affairs (VA) administrative data and Medicare claims in 2001-2004 for 11,123 Medicare-eligible VA primary care users in 2000. Study DesignWe compared means and distributions of VA reliance (the proportion of all VA/Medicare primary care visits occurring in VA) predicted from beta-binomial, binomial, and ordinary least-squares (OLS) models. Principal FindingsBeta-binomial model fits the bimodal distribution of VA reliance better than binomial and OLS models due to the nondependence on normality and the greater flexibility in shape parameters. ConclusionsIncreased awareness of beta-binomial regression may help analysts apply appropriate methods to outcomes with bimodal or U-shaped distributions. C1 [Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98108 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Manning, Willard G.] Univ Chicago, Chicago, IL 60637 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Chuan-Fen.Liu@va.gov FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 04-292]; Department of Veterans Affairs [RCS 10-391] FX This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 04-292. Dr. Maciejewski was also supported by a Research Career Scientist award from the Department of Veterans Affairs (RCS 10-391). The views expressed herein are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington, Boston University, the University of Chicago, and Duke University. NR 7 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2013 VL 48 IS 5 BP 1769 EP 1778 DI 10.1111/1475-6773.12055 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 225YF UT WOS:000325000400014 PM 23521600 ER PT J AU Chang, EW Cheng, JT Roosli, C Kobler, JB Rosowski, JJ Yun, SH AF Chang, Ernest W. Cheng, Jeffrey T. Roeoesli, Christof Kobler, James B. Rosowski, John J. Yun, Seok Hyun TI Simultaneous 3D imaging of sound-induced motions of the tympanic membrane and middle ear ossicles SO HEARING RESEARCH LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; HEARING-LOSS; LASER; CHINCHILLA; VELOCITY; SURFACE; EARDRUM; INTERFEROMETRY; FEASIBILITY AB Efficient transfer of sound by the middle ear ossicles is essential for hearing. Various pathologies can impede the transmission of sound and thereby cause conductive hearing loss. Differential diagnosis of ossicular disorders can be challenging since the ossicles are normally hidden behind the tympanic membrane (TM). Here we describe the use of a technique termed optical coherence tomography (OCT) vibrography to view the sound-induced motion of the TM and ossicles simultaneously. With this method, we were able to capture three-dimensional motion of the intact TM and ossicles of the chinchilla ear with nanometer-scale sensitivity at sound frequencies from 0.5 to 5 kHz. The vibration patterns of the TM were complex and highly frequency dependent with mean amplitudes of 70-120 nm at 100 dB sound pressure level. The TM motion was only marginally sensitive to stapes fixation and incus-stapes joint interruption; however, when additional information derived from the simultaneous measurement of ossicular motion was added, it was possible to clearly distinguish these different simulated pathologies. The technique may be applicable to clinical diagnosis in Otology and to basic research in audition and acoustics. (C) 2013 Elsevier B.V. All rights reserved. C1 [Chang, Ernest W.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Chang, Ernest W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Cheng, Jeffrey T.; Roeoesli, Christof; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Cheng, Jeffrey T.; Roeoesli, Christof; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Roeoesli, Christof] Univ Zurich Hosp, Dept Otorhinolaryngol Head & Neck Surg, Zurich, Switzerland. [Kobler, James B.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kobler, James B.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Rosowski, John J.; Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Yun, SH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu; syun@hms.harvard.edu FU Center for Biomedical OCT Research and Translation; National Institute of Health [P41EB015903, R01DC00194]; Wellman Center Graduate Student Scholarship FX This work was supported by the Center for Biomedical OCT Research and Translation funded by National Institute of Health (P41EB015903, R01DC00194). E.W.C. acknowledges the Wellman Center Graduate Student Scholarship. NR 41 TC 15 Z9 15 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 2013 VL 304 BP 49 EP 56 DI 10.1016/j.heares.2013.06.006 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 225PM UT WOS:000324974800007 PM 23811181 ER PT J AU Mandyam, MC Soliman, EZ Alonso, A Dewland, TA Heckbert, SR Vittinghoff, E Cummings, SR Ellinor, PT Chaitman, BR Stocke, K Applegate, WB Arking, DE Butler, J Loehr, LR Magnani, JW Murphy, RA Satterfield, S Newman, AB Marcus, GM AF Mandyam, Mala C. Soliman, Elsayed Z. Alonso, Alvaro Dewland, Thomas A. Heckbert, Susan R. Vittinghoff, Eric Cummings, Steven R. Ellinor, Patrick T. Chaitman, Bernard R. Stocke, Karen Applegate, William B. Arking, Dan E. Butler, Javed Loehr, Laura R. Magnani, Jared W. Murphy, Rachel A. Satterfield, Suzanne Newman, Anne B. Marcus, Gregory M. TI The QT interval and risk of incident atrial fibrillation SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Epidemiology; Risk; QT interval; Electrocardiogram; ECG ID CARDIOVASCULAR HEALTH; REFRACTORY PERIOD; DELAYED AFTERDEPOLARIZATIONS; ATHEROSCLEROSIS RISK; ASSOCIATION; HEART; PREVALENCE; ECG; CONTRIBUTES; ARRHYTHMIAS AB BACKGROUND Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine. OBJECTIVE To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF. METHODS We examined a prolonged QT interval corrected by using the Framingham formula (QTFram) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas. RESULTS Among 14,538 ARIC study participants, a prolonged QTFram predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QTFram was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts. CONCLUSION A prolonged QT interval is associated with an increased risk of incident AF. C1 [Mandyam, Mala C.; Dewland, Thomas A.; Marcus, Gregory M.] Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, San Francisco, CA 94143 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Epidemiol Cardiol Res Ctr, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cummings, Steven R.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Chaitman, Bernard R.] St Louis Univ, Sch Med, ECG Core Lab, St Louis, MO USA. [Stocke, Karen] St Louis Univ, Sch Med, ECG Core Lab, St Louis, MO USA. [Applegate, William B.] Wake Forest Univ, Sch Med, Div Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. [Arking, Dan E.] Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Butler, Javed] Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. [Loehr, Laura R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Magnani, Jared W.] Boston Univ, Cardiovasc Med Sect, Dept Med, Boston, MA 02215 USA. [Murphy, Rachel A.] Natl Inst Aging, Intramural Res Program, Lab Populat Sci, Bethesda, MD USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Marcus, GM (reprint author), Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, 505 Parnassus Ave,M-1180B,Box 0124, San Francisco, CA 94143 USA. EM marcusg@medicine.ucsf.edu RI Newman, Anne/C-6408-2013; Alonso, Alvaro/A-4917-2010 OI Newman, Anne/0000-0002-0106-1150; Alonso, Alvaro/0000-0002-2225-8323 FU University of California San Franciscos Clinical & Translational Science Institute (UCSF CTSI); National Center for Research Resources; National Center for Advancing Translational Sciences; Office of the Director, National Institutes of Health (NIH) [TL1 RR024129]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NHLBI [HHSN268201200036C, N01HC85239, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL068986]; National Institute on Aging (NIA) [AG023629]; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research grant [R01-NR012459]; Intramural Research Program of the NIH, NIA FX This research was supported by the following: For the University of California San Franciscos Clinical & Translational Science Institute (UCSF CTSI): the National Center for Research Resources, the National Center for Advancing Translational Sciences, and the Office of the Director, National Institutes of Health (NIH), through UCSF-CTSI grant number TL1 RR024129; for the Atherosclerosis Risk in Communities (ARIC) study: a collaborative support from National Heart, Lung, and Blood Institute (NHLBI) contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C; for the Cardiovascular Health Study (CHS): a support from NHLBI contracts HHSN268201200036C, N01HC85239, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants HL080295 and HL068986, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm; for the Health, Aging, and Body Composition (Health ABC) study: a support from NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and grant R01-AG028050, as well as the National Institute of Nursing Research grant R01-NR012459. This research was supported in part by the Intramural Research Program of the NIH, NIA. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of any of the supporting agencies or sources. NR 34 TC 15 Z9 16 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD OCT PY 2013 VL 10 IS 10 BP 1562 EP 1568 DI 10.1016/j.hrthm.2013.07.023 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 227XZ UT WOS:000325150300030 PM 23872693 ER PT J AU Chapman, LW Hsiao, JL Lewis, M Chiu, MW Shellow, WVR AF Chapman, Lance W. Hsiao, Jennifer L. Lewis, Michael Chiu, Melvin W. Shellow, William V. R. TI Progressive violaceous nodules and plaques in an elderly man SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article C1 [Chapman, Lance W.; Hsiao, Jennifer L.; Chiu, Melvin W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. [Lewis, Michael] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Lewis, Michael] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Lab Med, Los Angeles, CA USA. [Chiu, Melvin W.; Shellow, William V. R.] Vet Affairs West Los Angeles Healthcare Ctr, Dept Dermatol, Los Angeles, CA USA. RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, 200 Med Plaza,Suite 450, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD OCT PY 2013 VL 52 IS 10 BP 1165 EP 1167 DI 10.1111/ijd.12141 PG 3 WC Dermatology SC Dermatology GA 227EA UT WOS:000325090800001 PM 23834652 ER PT J AU Lennerz, JK Lauwers, GY AF Lennerz, Jochen K. Lauwers, Gregory Y. TI Amelanotic Adenoma SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Editorial Material ID MELANOSIS COLI C1 [Lennerz, Jochen K.] Univ Ulm, D-89081 Ulm, Germany. [Lennerz, Jochen K.; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lennerz, JK (reprint author), Univ Ulm, Inst Pathol, Albert Einstein Allee 23, D-89081 Ulm, Germany. EM jochen.lennerz@uni-ulm.de NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2013 VL 21 IS 5 BP 504 EP 505 DI 10.1177/1066896913496148 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA 222UH UT WOS:000324756700008 PM 23855023 ER PT J AU Dubsky, M Jirkovska, A Bem, R Fejfarova, V Skibova, J Schaper, NC Lipsky, BA AF Dubsky, Michal Jirkovska, Alexandra Bem, Robert Fejfarova, Vladimira Skibova, Jelena Schaper, Nicolaas C. Lipsky, Benjamin A. TI Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the Eurodiale subgroup SO INTERNATIONAL WOUND JOURNAL LA English DT Article DE Diabetic foot ulcer; Risk factors for reulceration; Ulcer recurrence ID PERIPHERAL ARTERIAL-DISEASE; COHORT; INFECTION; PEOPLE; CARE; POPULATION; ULCERATION; AMPUTATION; CONSENSUS; ISCHEMIA AB Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3-year follow-up period. At our site, 93 Eurodiale-enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes-related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU-related factors [peripheral arterial disease, ulcer infection, C-reactive protein (CRP) and; foot deformities]. During the 3-year follow-up period, a DFU had recurred in 42 patients (575%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 862, 95% confidence interval (CI) 22-332]; presence of osteomyelitis (OR 517, 95% CI 14-187); HbA1c > 75% ([DCCT], OR 407, 95% CI 11-156) and CRP > 5 mg/l (OR 427, 95% CI 12-157). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3-year follow-up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions. C1 [Dubsky, Michal; Jirkovska, Alexandra; Bem, Robert; Fejfarova, Vladimira; Skibova, Jelena] Inst Clin & Expt Med, Ctr Diabet, Prague 14021 4, Czech Republic. [Schaper, Nicolaas C.] Univ Hosp Maastricht, Dept Internal Med, Maastricht, Netherlands. [Lipsky, Benjamin A.] Univ Washington, Dept Med, Gen Med Serv, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Dubsky, M (reprint author), Inst Clin & Expt Med, Ctr Diabet, Videnska 1958-9, Prague 14021 4, Czech Republic. EM michal.dubsky@gmail.com RI Schaper, Nicolaas/E-7112-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114 FU [MZO 00023001] FX We thank the members of Eurodiale group for realisation of first step of the study: L. Prompers, M. Huijberts, J. Apelqvist, E. Jude, A. Piaggesi, K. Bakker, M. Edmonds, P. Holstein, D. Mauricio, G. Ragnarson Tennvall, H. Reike, M. Spraul, L. Uccioli, V. Urbancic, K. Van Acker, J. van Baal and F. van Merode. This research was supported by grant MZO 00023001. The authors do not have any competing interests. NR 33 TC 24 Z9 30 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-4801 J9 INT WOUND J JI Int. Wound J. PD OCT PY 2013 VL 10 IS 5 BP 555 EP 561 DI 10.1111/j.1742-481X.2012.01022.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 227DW UT WOS:000325090300013 PM 22712631 ER PT J AU Henderson, LA Frugoni, F Hopkins, G de Boer, H Pai, SY Lee, YN Walter, JE Hazen, MM Notarangelo, LD AF Henderson, Lauren A. Frugoni, Francesco Hopkins, Gregory de Boer, Helen Pai, Sung-Yun Lee, Yu Nee Walter, Jolan E. Hazen, Melissa M. Notarangelo, Luigi D. TI Expanding the spectrum of recombination-activating gene 1 deficiency: A family with early-onset autoimmunity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID RAG MUTATIONS; IMMUNODEFICIENCY; DEFECTS; DISEASE; CELLS C1 [Henderson, Lauren A.; Frugoni, Francesco; Lee, Yu Nee; Walter, Jolan E.; Hazen, Melissa M.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Hopkins, Gregory; de Boer, Helen; Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA USA. [Notarangelo, Luigi D.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Walter, Jolan E.] Massachusetts Gen Hosp Children, Div Pediat Allergy Immunol, Boston, MA USA. [Notarangelo, Luigi D.] Harvard Stem Cell Inst, Boston, MA USA. RP Henderson, LA (reprint author), Boston Childrens Hosp, Div Immunol, Boston, MA USA. EM Melissa.Hazen@childrens.harvard.edu; Luigi.Notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Frugoni, Francesco/0000-0002-1769-8121 FU NIAID NIH HHS [5P01AI076210-04, K08 AI103035, P01 AI076210, U54 AI082973, U54AI082973] NR 9 TC 19 Z9 19 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2013 VL 132 IS 4 BP 969 EP 971 DI 10.1016/j.jaci.2013.06.032 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 227FR UT WOS:000325096500025 PM 23891352 ER PT J AU Tang, YZ Xie, T Florian, S Moerke, N Shamu, C Benes, C Mitchison, TJ AF Tang, Yangzhong Xie, Tiao Florian, Stefan Moerke, Nathan Shamu, Caroline Benes, Cyril Mitchison, Timothy J. TI Differential Determinants of Cancer Cell Insensitivity to Antimitotic Drugs Discriminated by a One-Step Cell Imaging Assay SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE high-content screening; live cell imaging assay; image analysis; cancer cells; drug sensitivity; antimitotic drugs ID SMALL-MOLECULE INHIBITOR; INDUCED MITOTIC ARREST; POLO-LIKE KINASE-1; SENSITIVITY; POLO-LIKE-KINASE-1; IDENTIFICATION; RESISTANCE; DISCOVERY; KINESIN-5; APOPTOSIS AB Cancer cells can be drug resistant due to genetic variation at multiple steps in the drug response pathway, including drug efflux pumping, target mutation, and blunted apoptotic response. These are not discriminated by conventional cell survival assays. Here, we report a rapid and convenient high-content cell-imaging assay that measures multiple physiological changes in cells responding to antimitotic small-molecule drugs. Our one-step, no-wash assay uses three dyes to stain living cells and is much more accurate for scoring weakly adherent mitotic and apoptotic cells than conventional antibody-based assays. We profiled responses of 33 cell lines to 8 antimitotic drugs at multiple concentrations and time points using this assay and deposited our data and assay protocols into a public database (http://lincs.hms.harvard.edu/). Our data discriminated between alternative mechanisms that compromise drug sensitivity to paclitaxel and revealed an unexpected bell-shaped dose-response curve for BI2536, a highly selective inhibitor of Polo-like kinases. Our approach can be generalized, is scalable, and should therefore facilitate identification of molecular biomarkers for mechanisms of drug insensitivity in high-throughput screens and other assays. C1 [Tang, Yangzhong; Xie, Tiao; Florian, Stefan; Moerke, Nathan; Shamu, Caroline; Mitchison, Timothy J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Xie, Tiao] Harvard Univ, Sch Med, IDAC, Boston, MA 02115 USA. [Shamu, Caroline] Harvard Univ, Sch Med, ICCB Longwood Screening Facil, Boston, MA 02115 USA. [Benes, Cyril] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Xie, T (reprint author), Harvard Univ, Sch Med, 250 Longwood Ave,SGM604, Boston, MA 02115 USA. EM tiao_xie@hms.harvard.edu FU National Institutes of Health LINCS program [1U54HG006097-01] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health LINCS program, grant 1U54HG006097-01. NR 24 TC 2 Z9 2 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD OCT PY 2013 VL 18 IS 9 BP 1062 EP 1071 DI 10.1177/1087057113493804 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 222VO UT WOS:000324760300011 PM 23788527 ER PT J AU Tiouririne, M Baum, VC Battle, RW Arendt, KW Bhatt, AB AF Tiouririne, Mohamed Baum, Victor C. Battle, Robert W. Arendt, Katherine W. Bhatt, Ami B. TI Pregnant Patient With Uncorrected, Undiagnosed Total Anomalous Pulmonary Venous Return and Severe Pulmonary Hypertension SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE pregnancy; uncorrected cyanotic heart disease; total anomalous pulmonary venous return; pulmonary hypertension; epidural analgesia/anesthesia ID CONGENITAL HEART-DISEASE; ANESTHETIC MANAGEMENT; WOMEN; OUTCOMES; DELIVERY; RISKS C1 [Tiouririne, Mohamed; Baum, Victor C.] Univ Virginia, Sch Med, Dept Anesthesiol, Charlottesville, VA 22908 USA. [Battle, Robert W.] Univ Virginia, Sch Med, Dept Cardiol, Charlottesville, VA 22908 USA. [Arendt, Katherine W.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA. [Bhatt, Ami B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. RP Tiouririne, M (reprint author), Univ Virginia, Sch Med, Dept Anesthesiol, POB 800710, Charlottesville, VA 22908 USA. EM mt9y@virginia.edu OI Arendt, Katherine/0000-0002-4793-9133 NR 26 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2013 VL 27 IS 5 BP 1041 EP 1047 DI 10.1053/j.jvca.2013.02.010 PG 7 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 226SA UT WOS:000325055100026 PM 24054189 ER PT J AU Verjans, JW Jaffer, FA AF Verjans, Johan W. Jaffer, Farouc A. TI Biological Imaging of Atherosclerosis: Moving Beyond Anatomy SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Atherosclerosis; Molecular imaging; Vascular biology; Inflammation; Intravascular imaging; Fluorescence ID CORONARY-ARTERY-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; OPTICAL COHERENCE TOMOGRAPHY; CARDIOVASCULAR RISK-FACTORS; IN-VIVO; CAROTID-ARTERY; COMPUTED-TOMOGRAPHY; VULNERABLE PLAQUE; IRON-OXIDE AB Biological or molecular imaging is now providing exciting new strategies to study atherosclerosis in both animals and humans. These technologies hold the promise to provide disease-specific, molecular information within the context of a systemic or organ-specific disease beyond traditional anatomical-based imaging. By integration of biological, chemical, and anatomical imaging knowledge into diagnostic strategies, a more comprehensive and predictive picture of atherosclerosis is likely to emerge. As such, biological imaging is well positioned to study different stages of atherosclerosis and its treatment, including the sequence of atheroma initiation, progression, and plaque rupture. In this review, we describe the evolving concepts in atherosclerosis imaging with a focus on coronary artery disease, and we provide an overview of recent exciting translational developments in biological imaging. The illuminated examples and discussions will highlight how biological imaging is providing new clinical approaches to identify high-risk plaques, and to streamline the development process of new atherosclerosis therapies. C1 [Verjans, Johan W.; Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,Simches Bldg,Room 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Royal Netherlands Academy of Arts and Sciences [825.12.013]; NIH [R01 HL108229]; MGH SPARK Award; MGH ECOR Award FX Rubicon grant of the Royal Netherlands Academy of Arts and Sciences (825.12.013), NIH R01 HL108229, MGH SPARK Award, MGH ECOR Award. NR 84 TC 4 Z9 4 U1 0 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD OCT PY 2013 VL 6 IS 5 SI SI BP 681 EP 694 DI 10.1007/s12265-013-9474-z PG 14 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 229HK UT WOS:000325252900003 PM 23733542 ER PT J AU Erickson, MA Banks, WA AF Erickson, Michelle A. Banks, William A. TI Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE Alzheimer's disease; blood-brain barrier; cerebrospinal fluid; diabetes; inflammation; neurovascular unit ID AMYLOID-BETA-PROTEIN; CEREBROSPINAL-FLUID BARRIER; RECEPTOR-RELATED PROTEIN-1; ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; MILD COGNITIVE IMPAIRMENT; INDUCED DIABETIC MICE; WHITE-MATTER LESIONS; SMOOTH-MUSCLE-CELLS; P-GLYCOPROTEIN AB The blood-brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-beta (A beta) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of A beta pathology. C1 [Erickson, Michelle A.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Erickson, Michelle A.; Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. [Erickson, Michelle A.] Univ Penn, Sch Dent Med, Dept Pathol, Seattle, WA USA. RP Banks, WA (reprint author), Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Bldg 1,Room 810A,1660 Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU NIEHS NIH HHS [T32 ES019851] NR 237 TC 103 Z9 108 U1 5 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2013 VL 33 IS 10 BP 1500 EP 1513 DI 10.1038/jcbfm.2013.135 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 228PV UT WOS:000325199600004 PM 23921899 ER PT J AU Lin, AL Pulliam, DA Deepa, SS Halloran, JJ Hussong, SA Burbank, RR Bresnen, A Liu, YH Podlutskaya, N Soundararajan, A Muir, E Duong, TQ Bokov, AF Viscomi, C Zeviani, M Richardson, AG Van Remmen, H Fox, PT Galvan, V AF Lin, Ai-Ling Pulliam, Daniel A. Deepa, Sathyaseelan S. Halloran, Jonathan J. Hussong, Stacy A. Burbank, Raquel R. Bresnen, Andrew Liu, Yuhong Podlutskaya, Natalia Soundararajan, Anuradha Muir, Eric Duong, Timothy Q. Bokov, Alex F. Viscomi, Carlo Zeviani, Massimo Richardson, Arlan G. Van Remmen, Holly Fox, Peter T. Galvan, Veronica TI Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE glucose metabolism; memory; mitochondrial complex IV; mitochondrial dysfunction; Surf1 ID ELEGANS LIFE-SPAN; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; BINDING PROTEIN; FACTOR 1-ALPHA; RESPIRATION; SENSITIVITY; ANESTHESIA; INCREASES; LONGEVITY AB Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders. C1 [Lin, Ai-Ling; Bresnen, Andrew; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Lin, Ai-Ling; Pulliam, Daniel A.; Deepa, Sathyaseelan S.; Halloran, Jonathan J.; Hussong, Stacy A.; Burbank, Raquel R.; Liu, Yuhong; Podlutskaya, Natalia; Bokov, Alex F.; Richardson, Arlan G.; Van Remmen, Holly; Galvan, Veronica] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Lin, Ai-Ling; Pulliam, Daniel A.; Deepa, Sathyaseelan S.; Liu, Yuhong; Podlutskaya, Natalia; Bokov, Alex F.; Richardson, Arlan G.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Halloran, Jonathan J.; Hussong, Stacy A.; Burbank, Raquel R.; Podlutskaya, Natalia; Duong, Timothy Q.; Fox, Peter T.; Galvan, Veronica] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Viscomi, Carlo; Zeviani, Massimo] Ist Neurol C Besta, Mol Neurogenet Unit, Milan, Italy. [Richardson, Arlan G.; Van Remmen, Holly] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Richardson, Arlan G.; Van Remmen, Holly] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. RP Galvan, V (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM lina3@uthscsa.edu; galvanv@uthscsa.edu RI Duong, Timothy/B-8525-2008; Zeviani, Massimo/K-2891-2014; Fox, Peter/B-4725-2010; Viscomi, Carlo/R-1940-2016 OI Fox, Peter/0000-0002-0465-2028; FU Ellison Medical Foundation; William and Ella Owens Medical Research Foundation; CTSA/KL2 [UL1TR000149]; NIA [K01AG040164, T32AG21890] FX This work was supported by an Ellison Medical Foundation Senior Scholar Award in Aging and a New Scholar Award in Aging to HVR and VG, respectively, a William and Ella Owens Medical Research Foundation Grant to VG, and by CTSA/KL2 (UL1TR000149) and an NIA grant K01AG040164 to ALL. SAH is supported by NIA Training Grant T32AG21890. NR 33 TC 13 Z9 13 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2013 VL 33 IS 10 BP 1605 EP 1611 DI 10.1038/jcbfm.2013.116 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 228PV UT WOS:000325199600015 PM 23838831 ER PT J AU Faje, AT Nachtigall, L Wexler, D Miller, KK Klibanski, A Makimura, H AF Faje, Alexander T. Nachtigall, Lisa Wexler, Deborah Miller, Karen K. Klibanski, Anne Makimura, Hideo TI Central Diabetes Insipidus: A Previously Unreported Side Effect of Temozolomide SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POSTERIOR PITUITARY; MR-IMAGES; SIGNAL; GLAND AB Context: Temozolomide ( TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. Case Presentations: A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% ( 5 cases of diabetes insipidus per 1545 patients prescribed TMZ). Conclusions: Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ. C1 [Faje, Alexander T.; Nachtigall, Lisa; Miller, Karen K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Wexler, Deborah] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Faje, AT (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM afaje@partners.org FU Pfizer, Inc FX This work was supported by the National Institutes of Health Grant K23DK087857 (to H.M.).; H.M. has received investigator-initiated research support from Pfizer, Inc unrelated to the manuscript. The other authors have nothing to declare. NR 16 TC 2 Z9 5 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2013 VL 98 IS 10 BP 3926 EP 3931 DI 10.1210/jc.2013-2435 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230TM UT WOS:000325365900022 PM 23928668 ER PT J AU Goldberg, R Temprosa, M Otvos, J Brunzell, J Marcovina, S Mather, K Arakaki, R Watson, K Horton, E Barrett-Connor, E AF Goldberg, R. Temprosa, M. Otvos, J. Brunzell, J. Marcovina, S. Mather, K. Arakaki, R. Watson, K. Horton, E. Barrett-Connor, E. TI Lifestyle and Metformin Treatment Favorably Influence Lipoprotein Subfraction Distribution in the Diabetes Prevention Program SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; HEPATIC LIPASE; WEIGHT-LOSS; PLASMA-LIPOPROTEIN; INSULIN-RESISTANCE; METABOLIC SYNDROME; PARTICLE-SIZE AB Context: Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied. Objective: The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program. Design: This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT. Participants: Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study. Interventions: Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity. Main Outcome Measures: Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured. Results: ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance. Conclusion: ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also retard the progression of atherosclerosis. C1 [Goldberg, R.] Univ Miami, Leonard M Miller Sch Med, Miami, FL 33136 USA. [Temprosa, M.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Otvos, J.] LipoSci Inc, Raleigh, NC 27616 USA. [Brunzell, J.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Marcovina, S.] Univ Washington, NW Lipid Res Labs, Seattle, WA 98109 USA. [Mather, K.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. [Arakaki, R.] Univ Hawaii, Honolulu, HI 96813 USA. [Watson, K.] Univ Calif Los Angeles, Alhambra, CA 91801 USA. [Horton, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Barrett-Connor, E.] Univ Calif San Diego, San Diego, CA 92093 USA. RP Goldberg, R (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, 6110 Executive Blvd,Suite 750, Rockville, MD USA. EM dppmail@biostat.bsc.gwu.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK; University of Miami CTSA/GRECC program; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; McKesson BioServices Corp; Matthews Media Group, Inc; Henry M. Jackson Foundation FX This work was supported by The Diabetes Prevention Program, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which provided funding to the clinical centers and the coordinating center for the design and conduct of the study; and collection, management, analysis, and interpretation of the data; the National Institute of Child Health and Human Development and the National Institute on Aging; the Office of Research on Minority Health and Health Disparities, the Office of Research on Women's Health; the Indian Health Service; the Centers for Disease Control and Prevention; the General Clinical Research Program, the National Center for Research Resources; the American Diabetes Association; Bristol-Myers Squibb; Lipha Pharmaceuticals, Inc; and Parke-Davis. This work was also supported in part by the Intramural Research Program of the NIDDK and the University of Miami CTSA/GRECC program. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported the data collection at many of the clinical centers. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. LifeScan Inc, Health O Meter, Hoechst Marion Roussel, Inc, Merck-Medco Managed Care, Inc, Merck and Co, Nike Sports Marketing, Slim Fast Foods Co, and Quaker Oats Co donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp, Matthews Media Group, Inc, and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. NR 31 TC 22 Z9 22 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2013 VL 98 IS 10 BP 3989 EP 3998 DI 10.1210/jc.2013-1452 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230TM UT WOS:000325365900032 PM 23979954 ER PT J AU Coppadoro, A Berra, L Kumar, A Pinciroli, R Yamada, M Schmidt, UH Bittner, EA Kaneki, M AF Coppadoro, Andrea Berra, Lorenzo Kumar, Asheesh Pinciroli, Riccardo Yamada, Marina Schmidt, Ulrich H. Bittner, Edward A. Kaneki, Masao TI Critical illness is associated with decreased plasma levels of coenzyme Q10: A cross-sectional study SO JOURNAL OF CRITICAL CARE LA English DT Article DE Plasma coenzyme Q10; Critically ill patients; Septic shock; Sepsis; Age ID OXIDATIVE STRESS; HEALTHY-CHILDREN; HEART-FAILURE; ORGAN FAILURE; SEPTIC SHOCK; BLOOD-CELLS; Q(10); ADULTS; PLATELETS; OUTCOMES AB Purpose: Plasma coenzyme Q10 (CoQ10) levels are lower in patients with septic shock (SS) than in healthy controls (HCs). However, CoQ10 status in critically ill patients without SS is unknown. Here, we investigated CoQ10 concentrations in patients with SS and without SS as compared with HCs. Materials and Methods: We enrolled 36 critically ill patients and 18 HCs. Plasma CoQ10 concentrations were measured, and patients' clinical and demographical data were collected. Results: Plasma CoQ10 concentrations were lower in critically ill patients (0.50 +/- 0.36 mu g/mL, P < .001), both in patients with SS (0.37 +/- 0.25 mu g/mL, P = .002) and patients without SS (0.56 +/- 0.39, P = .04), as compared with HCs (0.79 +/- 0.19). Coenzyme Q10 levels did not differ between patients with SS and patients without SS (P = .13). In critically ill patients, CoQ10 levels inversely correlated with age (r = -0.40, P = .015) and did not correlate with partial pressure of oxygen in the arterial blood/fraction of inspired oxygen, Simplified Acute Physiology Score II, Systemic Organ Failure Assessment score, or mortality. Lower CoQ10 levels were associated with lower activities of daily living score after discharge (P = .005), independent of age. Conclusions: Decreased plasma CoQ10 levels are not specific to patients with SS, but rather observed in a broad range of critically ill patients. In critically ill patients, CoQ10 insufficiency may be associated with various conditions; age may be a risk factor. (C) 2013 Elsevier Inc. All rights reserved. C1 [Coppadoro, Andrea; Berra, Lorenzo; Kumar, Asheesh; Pinciroli, Riccardo; Yamada, Marina; Schmidt, Ulrich H.; Bittner, Edward A.; Kaneki, Masao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Yamada, Marina; Kaneki, Masao] Shriners Hosp Children, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02111 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu FU Shriners Hospitals for Children FX We are grateful to Dr J.P. Cobb for organizing this research team. This study was supported, in part, by grants from Shriners Hospitals for Children to M.K. NR 34 TC 2 Z9 2 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD OCT PY 2013 VL 28 IS 5 BP 571 EP 576 DI 10.1016/j.jcrc.2013.02.009 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 217QM UT WOS:000324374700006 PM 23618779 ER PT J AU Golenia, BS Levine, AR Moawad, IM Yeh, DD Arpino, PA AF Golenia, Brandy S. Levine, Alexander R. Moawad, Iman M. Yeh, D. Dante Arpino, Paul A. TI Evaluation of a vancomycin dosing nomogram based on the Modification of Diet in Renal Disease equation in intensive care unit patients SO JOURNAL OF CRITICAL CARE LA English DT Article DE Vancomycin; ICU; Dosing nomogram; Antibiotics ID VENTILATOR-ASSOCIATED PNEUMONIA; CRITICALLY-ILL PATIENTS; KIDNEY-FUNCTION; OUTCOMES; GUIDELINES AB Purpose: The purpose of the study is to evaluate the effectiveness of a vancomycin nomogram using actual body weight and the Modification of Diet in Renal Disease equation to estimate renal function in intensive care unit patients. Methods: Retrospective evaluation (preimplementation group, n = 57) was conducted from March 2011 to April 2011. Prospective evaluation was conducted after nomogram implementation (postimplementation group, n = 60) from December 2011 to February 2012. Results: The percentage of patients with an initial vancomycin trough concentration 15 mu g/mL or higher increased in the postimplementation group as compared with the preimplementation group (72% vs 39%, P = .0004). The postimplementation group also demonstrated an increase in the percentage of patients with initial trough concentration between 15 and 20 mu g/mL (42% vs 19%, P = .0099), and no statistical difference in the percentage of patients with an initial trough greater than 20 mu g/mL (30% vs 19%, P = .2041). There was no difference in nephrotoxicity in the postimplementation group compared with the preimplementation group (18% vs 17.5%, P = 1.0). Conclusion: Use of a vancomycin nomogram increased the percentage of initial vancomycin trough concentrations 15 mu g/mL or higher in intensive care unit patients and was not associated with an increased occurrence of nephrotoxicity. (C) 2013 Elsevier Inc. All rights reserved. C1 [Golenia, Brandy S.; Levine, Alexander R.; Moawad, Iman M.; Arpino, Paul A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Yeh, D. Dante] Massachusetts Gen Hosp, Dept Trauma Emergency Surg & Surg Crit Car, Boston, MA 02114 USA. RP Arpino, PA (reprint author), Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. EM parpino@partners.org NR 19 TC 6 Z9 6 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD OCT PY 2013 VL 28 IS 5 BP 710 EP 716 DI 10.1016/j.jcrc.2013.01.004 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 217QM UT WOS:000324374700025 PM 23499418 ER PT J AU Levine, AR Meyer, MJ Bittner, EA Berg, S Kalman, R Stanislaus, AB Ryan, C Ball, SA Eikermann, M AF Levine, Alexander R. Meyer, Matthew J. Bittner, Edward A. Berg, Sheri Kalman, Rebecca Stanislaus, Anne B. Ryan, Cheryl Ball, Stephanie A. Eikermann, Matthias TI Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions SO JOURNAL OF CRITICAL CARE LA English DT Article DE Midodrine; Hypotension; Intravenous vasopressors; Intensive care unit; ICU discharge ID NEUROGENIC ORTHOSTATIC HYPOTENSION; INFLAMMATORY RESPONSE SYNDROME; DOUBLE-BLIND; SURGERY; THERAPY; PLACEBO AB Purpose: Persistent low-level hypotension represents a barrier to discharging patients from the intensive care unit (ICU). Midodrine may be an effective adjunct to wean intravenous (IV) vasopressors and permit ICU discharge. We tested the hypothesis that midodrine, given to patients on IV vasopressors who otherwise met ICU discharge criteria, increased the magnitude of change in IV vasopressor rate. Materials and Methods: This was a prospective, observational study in 20 adult surgical ICU patients who met ICU discharge criteria except for an IV vasopressor requirement. We compared the change in phenylephrine equivalent rates during the day before midodrine to the change in phenylephrine equivalent rates after midodrine initiation and analyzed changes in total body fluid balance, heart rate, mean arterial pressure, and white blood cell count during this period. Results: Patients received 41.0 +/- 33.4 mu g/min of phenylephrine equivalents and the change in IV vasopressor rate (slope) decreased significantly from -0.62 mu g/min per hour of phenylephrine equivalents before midodrine to -2.20 mu g/min per hour following the initiation of midodrine treatment (P = .012). Change in total body fluid balance, heart rate, mean arterial pressure, and white blood cell count did not correlate with change in IV vasopressor rate. Conclusion: Midodrine treatment was associated with an increase in the magnitude of decline of the IV vasopressor rate. Oral midodrine may facilitate liberation of surgical ICU patients from an IV vasopressor infusion, and this may affect discharge readiness of patients from the ICU. (C) 2013 Elsevier Inc. All rights reserved. C1 [Levine, Alexander R.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Meyer, Matthew J.; Bittner, Edward A.; Berg, Sheri; Kalman, Rebecca; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bittner, Edward A.; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Stanislaus, Anne B.; Ryan, Cheryl; Ball, Stephanie A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eikermann, Matthias] Univ Duisburg Essen, Duisburg, Germany. RP Meyer, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM mjmeyer@partners.org NR 22 TC 7 Z9 7 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 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD OCT PY 2013 VL 28 IS 5 BP 756 EP 762 DI 10.1016/j.jcrc.2013.05.021 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 217QM UT WOS:000324374700031 PM 23845791 ER PT J AU Susilo, T Germine, L Duchaine, B AF Susilo, Tirta Germine, Laura Duchaine, Bradley TI Face Recognition Ability Matures Late: Evidence From Individual Differences in Young Adults SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE LA English DT Article DE face recognition; cognitive development; visual development; late maturation; individual differences ID MEMORY TEST; PROSOPAGNOSIA; CHILDREN; SEX AB Does face recognition ability mature early in childhood (early maturation hypothesis) or does it continue to develop well into adulthood (late maturation hypothesis)? This fundamental issue in face recognition is typically addressed by comparing child and adult participants. However, the interpretation of such studies is complicated by children's inferior test-taking abilities and general cognitive functions. Here we examined the developmental trajectory of face recognition ability in an individual differences study of 18-33 year-olds (n = 2,032), an age interval in which participants are competent test takers with comparable general cognitive functions. We found a positive association between age and face recognition, controlling for nonface visual recognition, verbal memory, sex, and own-race bias. Our study supports the late maturation hypothesis in face recognition, and illustrates how individual differences investigations of young adults can address theoretical issues concerning the development of perceptual and cognitive abilities. C1 [Susilo, Tirta; Duchaine, Bradley] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. [Germine, Laura] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Cambridge, MA 02138 USA. RP Susilo, T (reprint author), Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. EM bagus.t.susilo@dartmouth.edu RI Susilo, Tirta/S-1558-2016; OI Susilo, Tirta/0000-0002-1130-3475; Germine, Laura/0000-0001-8690-8412 NR 29 TC 16 Z9 16 U1 4 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-1523 J9 J EXP PSYCHOL HUMAN JI J. Exp. Psychol.-Hum. Percept. Perform. PD OCT PY 2013 VL 39 IS 5 BP 1212 EP 1217 DI 10.1037/a0033469 PG 6 WC Psychology; Psychology, Experimental SC Psychology GA 229FQ UT WOS:000325247600002 PM 23915172 ER PT J AU Iverson, KM King, MW Resick, PA Gerber, MR Kimerling, R Vogt, D AF Iverson, Katherine M. King, Matthew W. Resick, Patricia A. Gerber, Megan R. Kimerling, Rachel Vogt, Dawne TI Clinical Utility of an Intimate Partner Violence Screening Tool for Female VHA Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diagnostic accuracy; sensitivity and specificity; partner abuse; screening; women veterans ID POSTTRAUMATIC-STRESS-DISORDER; DOMESTIC VIOLENCE; MENTAL-HEALTH; ABUSED WOMEN; VALIDITY; IMPACT AB Female Veterans are at high risk for physical, sexual, and psychological forms of intimate partner violence (IPV) victimization. This study evaluated the accuracy of a brief IPV victimization screening tool for use with female Veterans Health Administration (VHA) patients. Participants completed a paper-and-pencil mail survey that included the four-item Hurt/Insult/Threaten/Scream (HITS) and the 39-item Revised Conflict Tactics Scales (CTS-2). Operating characteristics, including sensitivity and specificity, were calculated using the CTS-2 as the reference standard for past-year IPV. Female veterans from a roster of randomly selected female patients of the New England VA Healthcare System. Women must have reported being in an intimate relationship in the past year to be included. Primary measures included the HITS (index test) and the CTS-2 (reference standard). This study included 160 women. The percentage of women who reported past-year IPV, as measured by any physical assault, sexual coercion, and/or severe psychological aggression on the CTS-2, was 28.8 %. The receiver-operator characteristic curve demonstrated that the HITS cutoff score of 6 maximizes the true positives while minimizing the false positives in this sample. The sensitivity of the optimal HITS cutoff score of 6 was 78 % (95 % CI 64 % to 88 %), specificity 80 % (95 % CI 71 % to 87 %), positive likelihood ratio 3.9 (95 % CI 2.61 to 5.76), negative likelihood ratio 0.27 (95 % CI 0.16 to 0.47), positive predictive value 0.61 (95 % CI 0.47, 0.73), and negative predictive value 0.90 (95 % CI 0.82, 0.95). For a low-burden screen, the HITS demonstrated good accuracy in detecting past-year IPV relative to the CTS-2 in a sample of female VHA patients with an optimal cutpoint of 6. The HITS may help VHA and other health-care providers detect past-year IPV and deliver appropriate care for female Veterans. C1 [Iverson, Katherine M.; King, Matthew W.; Resick, Patricia A.; Vogt, Dawne] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Iverson, Katherine M.; Resick, Patricia A.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Gerber, Megan R.] VA Boston Healthcare Syst, Womens Hlth, Boston, MA 02130 USA. [Gerber, Megan R.] Boston Univ, Sch Med, Dept Gen Internal Med, Boston, MA 02118 USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 South Huntington Ave,116B-3, Boston, MA 02130 USA. EM Katherine.Iverson@va.gov OI Gerber, Megan/0000-0002-8444-5554; Kimerling, Rachel/0000-0003-0996-4212 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of Dr. Katherine Iverson's HSR&D Career Development Award [CDA10-029] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of Dr. Katherine Iverson's HSR&D Career Development Award (CDA10-029). 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 US government. NR 37 TC 17 Z9 17 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2013 VL 28 IS 10 BP 1288 EP 1293 DI 10.1007/s11606-013-2534-x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 226DP UT WOS:000325015000012 PM 23824907 ER PT J AU Goetz, MB Hoang, T Knapp, H Burgess, J Fletcher, MD Gifford, AL Asch, SM AF Goetz, Matthew Bidwell Tuyen Hoang Knapp, Herschel Burgess, Jane Fletcher, Michael D. Gifford, Allen L. Asch, Steven M. CA QUERI-HIV-Hepatitis Program TI Central Implementation Strategies Outperform Local Ones in Improving HIV Testing in Veterans Healthcare Administration Facilities SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV/AIDS; implementation research; quality improvement; diagnosis ID UNITED-STATES; PRACTICE GUIDELINES; COST-EFFECTIVENESS; FEEDBACK; AUDIT; ADOLESCENTS; REMINDERS; SETTINGS; ADULTS; TRIAL AB Pilot data suggest that a multifaceted approach may increase HIV testing rates, but the scalability of this approach and the level of support needed for successful implementation remain unknown. To evaluate the effectiveness of a scaled-up multi-component intervention in increasing the rate of risk-based and routine HIV diagnostic testing in primary care clinics and the impact of differing levels of program support. Three arm, quasi-experimental implementation research study. Veterans Health Administration (VHA) facilities. Persons receiving primary care between June 2009 and September 2011 A multimodal program, including a real-time electronic clinical reminder to facilitate HIV testing, provider feedback reports and provider education, was implemented in Central and Local Arm Sites; sites in the Central Arm also received ongoing programmatic support. Control Arm sites had no intervention Frequency of performing HIV testing during the 6 months before and after implementation of a risk-based clinical reminder (phase I) or routine clinical reminder (phase II). The adjusted rate of risk-based testing increased by 0.4 %, 5.6 % and 10.1 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). During phase II, the adjusted rate of routine testing increased by 1.1 %, 6.3 % and 9.2 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). At study end, 70-80 % of patients had been offered an HIV test. Use of clinical reminders, provider feedback, education and social marketing significantly increased the frequency at which HIV testing is offered and performed in VHA facilities. These findings support a multimodal approach toward achieving the goal of having every American know their HIV status as a matter of routine clinical practice. C1 [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Tuyen Hoang; Knapp, Herschel; Burgess, Jane; Fletcher, Michael D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem Vet Hosp, VA Bedford Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Gifford, Allen L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Asch, Steven M.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. RP Goetz, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mgoetz@ucla.edu OI Goetz, Matthew/0000-0003-4542-992X FU Health Services Research & Development Service [SDP 08-002] FX We acknowledge and are grateful for the invaluable support for this project that was provided by Ana Goffin, Barbara Kertz, Thomas Giordano, MD, and Scott Sherman, MD, MPH, as well as the providers and leadership in the many VHA medical facilities that participated in this study. This project was supported by a research grant to Drs. Goetz and Asch by the Health Services Research & Development Service (SDP 08-002). NR 37 TC 14 Z9 14 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2013 VL 28 IS 10 BP 1311 EP 1317 DI 10.1007/s11606-013-2420-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 226DP UT WOS:000325015000015 PM 23605307 ER PT J AU Steinhilber, S Rodriguez, JM Estrada, CA Kraemer, RR AF Steinhilber, Starr Rodriguez, J. Martin Estrada, Carlos A. Kraemer, Ryan R. TI A 76-Year-Old Woman with Diaphoresis and Anxiety SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID METACOGNITION; PERCEPTIONS; PERSPECTIVE; STRATEGIES; EXPERTISE; MODEL C1 [Steinhilber, Starr; Kraemer, Ryan R.] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Birmingham, AL 35294 USA. [Rodriguez, J. Martin; Estrada, Carlos A.; Kraemer, Ryan R.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.; Kraemer, Ryan R.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] Vet Affairs Qual Scholars Program, Birmingham, AL USA. RP Kraemer, RR (reprint author), Univ Alabama Birmingham, Dept Med, 720 Fac Off Tower 510 20th St, Birmingham, AL 35294 USA. EM rkraemer@uab.edu NR 23 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2013 VL 28 IS 10 BP 1376 EP 1380 DI 10.1007/s11606-013-2500-7 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 226DP UT WOS:000325015000026 PM 23729373 ER PT J AU Denby, K Nelson, G Estrada, CA AF Denby, Kara Nelson, George Estrada, Carlos A. TI Bedside Hand Grip Assessment with the Sphygmomanometer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE physical examination; hand Strength; muscle strength dynamometer C1 [Denby, Kara; Nelson, George; Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Nelson, George] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Qual Scholars Program, Birmingham, AL USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Div Gen Internal Med, 732 Fac Off Tower,510 20th St South, Birmingham, AL 35294 USA. EM cestrada@uab.edu NR 2 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2013 VL 28 IS 10 BP 1381 EP 1381 DI 10.1007/s11606-013-2426-0 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 226DP UT WOS:000325015000027 PM 23568188 ER PT J AU Esteves, WAM Lodi-Junqueira, L Neto, CPF Tan, TC Nascimento, BR Mehrotra, P Barbosa, MM Ribeiro, ALP Nunes, MCP AF Esteves, William A. M. Lodi-Junqueira, Lucas Fonseca Neto, Cirilo P. Tan, Timothy C. Nascimento, Bruno R. Mehrotra, Praveen Barbosa, Marcia M. Ribeiro, Antonio Luiz P. Nunes, Maria Carmo P. TI The Impact of Right Ventricular Stroke Work on B-Type Natriuretic Peptide Levels in Patients With Mitral Stenosis Undergoing Percutaneous Mitral Valvuloplasty SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID PULMONARY-HYPERTENSION; BALLOON CATHETER; PLASMA-LEVELS; RISK SCORE; ATRIAL; BRAIN; DYSFUNCTION; VALVE; COMMISSUROTOMY; PRESSURE AB ObjectivesWe aimed to explore the relationship between brain natriuretic peptide (BNP) levels and right ventricular (RV) function in patients with mitral stenosis (MS), and to investigate the hemodynamic parameters that predict reduction of BNP levels after percutaneous mitral valvuloplasty (PMV). BackgroundFew studies have evaluated BNP in the context of MS, specifically the impact of the RV stroke work (RVSW) on serum BNP levels has not been defined. MethodsThirty patients with symptomatic rheumatic MS in sinus rhythm who were referred for a PMV were enrolled. Right and left heart pressures were obtained before and after valvuloplasty. RVSW index (RVSWI) was calculated by cardiac catheterization. ResultsBasal BNP levels were elevated in MS patients and correlated with several hemodynamic parameters including pulmonary pressure, pulmonary vascular resistance index, cardiac index (CI), and RVSWI. In multivariate analysis, CI and RVSWI were independent predictors of raised basal BNP levels. PMV resulted in a significant decrease in the RVSWI with a concurrent increase in CI (2.40.43 to 2.9 +/- 0.8L/min/m(2), P=0.010). Overall, plasma BNP levels significantly decreased from 124 (63/234) to 73 (48/148)pg/ml postvalvuloplasty. Multivariate analysis revealed that the reduction of left atrial (LA) pressure post-PMV was an independent predictor of change in BNP levels. ConclusionsElevated baseline BNP level in MS patients was independently associated with CI and RVSWI. Plasma BNP levels were reduced after successful PMV, which was associated with the reduction of the LA pressure. (J Interven Cardiol 2013;26:501-508) C1 [Esteves, William A. M.; Ribeiro, Antonio Luiz P.; Nunes, Maria Carmo P.] Univ Fed Minas Gerais, Sch Med, Postgrad Program Infect Dis & Trop Med, BR-30130100 Belo Horizonte, MG, Brazil. [Lodi-Junqueira, Lucas; Fonseca Neto, Cirilo P.; Nascimento, Bruno R.; Barbosa, Marcia M.; Ribeiro, Antonio Luiz P.; Nunes, Maria Carmo P.] Univ Fed Minas Gerais, Sch Med, Hosp Clin, BR-30130100 Belo Horizonte, MG, Brazil. [Tan, Timothy C.; Mehrotra, Praveen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Nunes, MCP (reprint author), Univ Fed Minas Gerais, Sch Med, Dept Internal Med, Av Prof Alfredo Balena 190, BR-30130100 Belo Horizonte, MG, Brazil. EM mcarmo@waymail.com.br RI Ribeiro, Antonio/C-2707-2009 OI Ribeiro, Antonio/0000-0002-2740-0042 FU Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brasilia, Brazil; Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Belo Horizonte, Brazil FX This study was partly supported by grants from Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brasilia, Brazil, and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Belo Horizonte, Brazil. NR 30 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 2013 VL 26 IS 5 BP 501 EP 508 DI 10.1111/joic.12050 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 232FX UT WOS:000325478600009 PM 23879382 ER PT J AU Spiltoir, JI Stratton, MS Cavasin, MA Demos-Davies, K Reid, BG Qi, J Bradner, JE McKinsey, TA AF Spiltoir, Jessica I. Stratton, Matthew S. Cavasin, Maria A. Demos-Davies, Kim Reid, Brian G. Qi, Jun Bradner, James E. McKinsey, Timothy A. TI BET acetyl-lysine binding proteins control pathological cardiac hypertrophy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Cardiac hypertrophy; BET protein; Acetyl-lysine ID AMERICAN-HEART-ASSOCIATION; ELONGATION-FACTOR-B; LINEAGE PROTEIN-1; P-TEFB; TRANSCRIPTION; DISEASE; BROMODOMAINS; UPDATE AB Cardiac hypertrophy is an independent predictor of adverse outcomes in patients with heart failure, and thus represents an attractive target for novel therapeutic intervention. JQ1, a small molecule inhibitor of bromodomain and extraterminal (BET) acetyl-lysine reader proteins, was identified in a high throughput screen designed to discover novel small molecule regulators of cardiomyocyte hypertrophy. JQ1 dose-dependently blocked agonist-dependent hypertrophy of cultured neonatal rat ventricular myocytes (NRVMs) and reversed the prototypical gene program associated with pathological cardiac hypertrophy. JQ1 also blocked left ventricular hypertrophy (LVH) and improved cardiac function in adult mice subjected to transverse aortic constriction (TAC). The BET family consists of BRD2, BRD3, BRD4 and BRDT. BRD4 protein expression was increased during cardiac hypertrophy, and hypertrophic stimuli promoted recruitment of BRD4 to the transcriptional start site (TSS) of the gene encoding atrial natriuretic factor (ANF). Binding of BRD4 to the ANF TSS was associated with increased phosphorylation of local RNA polymerase II. These findings define a novel function for BET proteins as signal-responsive regulators of cardiac hypertrophy, and suggest that small molecule inhibitors of these epigenetic reader proteins have potential as therapeutics for heart failure. (C) 2013 Published by Elsevier Ltd. C1 [Spiltoir, Jessica I.; Stratton, Matthew S.; Cavasin, Maria A.; Demos-Davies, Kim; McKinsey, Timothy A.] Univ Colorado Denver, Dept Med, Div Cardiol, Aurora, CO USA. [Spiltoir, Jessica I.; McKinsey, Timothy A.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO USA. [Reid, Brian G.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP McKinsey, TA (reprint author), Univ Colorado Denver, Dept Med, Div Cardiol, Aurora, CO USA. EM timothy.mckinsey@ucdenver.edu FU NIH [5T32GM007635-34, 5T32HL007822-12]; University of Colorado Denver FX J.I.S. was supported by a predoctoral T32 training grant from the NIH (5T32GM007635-34). M.S.S. was supported by a postdoctoral T32 training grant from the NIH (5T32HL007822-12). Other support for the work was provided by start-up funds to T.A.M. from the University of Colorado Denver. NR 13 TC 41 Z9 41 U1 0 U2 32 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD OCT PY 2013 VL 63 BP 175 EP 179 DI 10.1016/j.yjmcc.2013.07.017 PG 5 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 231BF UT WOS:000325387300020 PM 23939492 ER PT J AU Sakamoto, M Woods, SP Kolessar, M Kriz, D Anderson, JR Olavarria, H Sasaki, AW Chang, M Flora, KD Loftis, JM Huckans, M AF Sakamoto, Maiko Woods, Steven Paul Kolessar, Michael Kriz, Daniel Anderson, J. Renee Olavarria, Hannah Sasaki, Anna W. Chang, Michael Flora, Kenneth D. Loftis, Jennifer M. Huckans, Marilyn TI Protective effects of higher cognitive reserve for neuropsychological and daily functioning among individuals infected with hepatitis C SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Hepatitis C; Cognitive reserve; Neuropsychological assessment; Daily functioning ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; VIRUS-INFECTION; ALZHEIMERS-DISEASE; DSM-IV; HIV; IMPAIRMENT; RISK; METHAMPHETAMINE AB Higher levels of cognitive reserve (CR) can be protective against the neuropsychological manifestation of neural injury across a variety of clinical disorders. However, the role of CR in the expression of neurocognitive deficits among persons infected with the hepatitis C virus (HCV) is not well understood. Thirty-nine HCV-infected participants were classified as having either high (n = 19) or low (n = 20) CR based on educational attainment, oral word reading, and IQ scores. A sample of 40 demographically comparable healthy adults (HA) was also included. All participants completed the Neuropsychological Assessment Battery, Delis-Kaplan Executive Function System, and Behavioral Rating Inventory of Executive Function, Adult Version (BRIEF-A). Linear regression analyses, controlling for gender, depression, and lifetime substance use disorders, found significant effects of HCV/CR group on verbal fluency, executive functions, and daily functioning T scores, but not in learning or the BRIEF-A. Pairwise comparisons revealed that the HCV group with low CR performed significantly below the HCV high CR and HA cohorts, who did not differ from one another. Findings indicate that higher levels of CR may be a protective factor in the neurocognitive and real-world manifestation of neural injury commonly associated with HCV infection. C1 [Sakamoto, Maiko; Woods, Steven Paul] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Kolessar, Michael; Kriz, Daniel; Anderson, J. Renee] Univ Pacific, Sch Profess Psychol, Hillsboro, OR 97123 USA. [Kriz, Daniel] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97239 USA. [Olavarria, Hannah; Loftis, Jennifer M.; Huckans, Marilyn] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Sasaki, Anna W.; Chang, Michael] Portland VA Med Ctr, Gastroenterol Serv, Portland, OR 97239 USA. [Chang, Michael] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97239 USA. [Flora, Kenneth D.] Oregon Clin, Portland Gastroenterol Div, Clackamas, OR 97015 USA. [Loftis, Jennifer M.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Huckans, Marilyn] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Huckans, Marilyn] Portland VA Med Ctr, Portland, OR 97239 USA. RP Huckans, M (reprint author), Portland VA Med Ctr, Mailstop P3MHN,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM marilyn.huckans@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development [R25-MH081482] FX This study was supported in part by R25-MH081482 to MS as well as by career development awards to MH and JML from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development. This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center, Portland, OR. The authors thank the study participants and staff at each of the recruitment sites, especially Betsy Zucker and Janice Voukidis. The authors also acknowledge Peter Hauser, William Hoffman, Diane Howieson, Daniel Storzbach, and Alexander Stevens for study design consultation. NR 55 TC 6 Z9 6 U1 4 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2013 VL 19 IS 5 BP 442 EP 451 DI 10.1007/s13365-013-0196-4 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 228YM UT WOS:000325228100005 PM 24018902 ER PT J AU Lopez, X Goldfine, AB Holland, WL Gordillo, R Scherer, PE AF Lopez, Ximena Goldfine, Allison B. Holland, William L. Gordillo, Ruth Scherer, Philipp E. TI Plasma ceramides are elevated in female children and adolescents with type 2 diabetes SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE adolescents; ceramides; children; insulin resistance; obesity; type 2 diabetes ID INDUCED INSULIN-RESISTANCE; SKELETAL-MUSCLE; OBESITY; ADIPONECTIN; INHIBITION; METABOLISM; MICE AB Accumulation of ceramides within tissues induces insulin resistance. Moreover, adiponectin exerts its beneficial metabolic effects at least partially through ceramide catabolism. We hypothesized that specific plasma ceramide subspecies are elevated in obese children and adolescents with type 2 diabetes (T2D), and that they inversely correlate with adiponectin and measures of insulin sensitivity. This was a cross-sectional study. Participants included 14 obese female subjects with T2D, ages 10-17, and 14 lean healthy controls of the same age and gender. Fasting plasma ceramide subspecies were measured by quantitative tandem mass spectrometry. Subjects with T2D had higher concentrations of C22:0 and C20:0 ceramides, with a 2-fold increase in C18:0 ceramide and C24:1 dihydroceramide (p<0.05). C22: 0, C20: 0 and C18: 0 ceramide correlated with decreased adiponectin concentrations, increased HOMA-IR, BMI Z-score, triglyceride and fasting blood glucose concentrations (p<0.05). Plasma levels of C18: 0, C20: 0 and C22: 0 ceramide, as well as C24: 1 dihydroceramide, were elevated in obese female children and adolescents with T2D. This may be a reflection of tissue insulin resistance and could be a result of low adiponectin levels. C1 [Lopez, Ximena] Univ Texas Southwestern, Dallas, TX 75390 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Holland, William L.; Gordillo, Ruth; Scherer, Philipp E.] Univ Texas Southwestern, Touchstone Diabet Ctr, Dallas, TX 75390 USA. RP Lopez, X (reprint author), Univ Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM ximena.lopez@utsouthwestern.edu NR 12 TC 20 Z9 20 U1 2 U2 9 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD OCT PY 2013 VL 26 IS 9-10 BP 995 EP 998 DI 10.1515/jpem-2012-0407 PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 228RI UT WOS:000325204500035 PM 23612696 ER PT J AU Kelly, ME Lu, XM Devidas, M Camitta, B Abshire, T Bernstein, ML Billett, A Homans, A Sandler, E Buchanan, G AF Kelly, Michael E. Lu, Xiaomin Devidas, Meenakshi Camitta, Bruce Abshire, Thomas Bernstein, Mark L. Billett, Amy Homans, Alan Sandler, Eric Buchanan, George TI Treatment of Relapsed Precursor-B Acute Lymphoblastic Leukemia With Intensive Chemotherapy: POG (Pediatric Oncology Group) Study 9411 (SIMAL 9) SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE relapsed precursor-B; ALL; intensive chemotherapy; POG study 9411; SIMAL 9 ID MATCHED SIBLING TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MARROW-TRANSPLANT; 2ND REMISSION; 1ST RELAPSE; CHILDREN; CHILDHOOD; TRIAL; MITOXANTRONE; OUTCOMES AB Pediatric patients who experience a bone marrow relapse of precursor-B acute lymphoblastic leukemia are cured <50% of the time. This study was designed to determine if intensification of therapies with known activity in this disease would improve the cure rates for patients with relapsed acute lymphoblastic leukemia. Patients were treated with intensive asparaginase during induction followed by repeated cycles of ifosfamide/etoposide and cytarabine/idarubicin. Patients with well-matched related donors were encouraged to undergo hematopoietic stem cell transplant as consolidation. The results of this study demonstrate no significant difference in disease-free survival in patients who received chemotherapy alone (45%) or chemotherapy followed by allogeneic stem cell transplant (50%). Furthermore, results from this study show no significant difference in event-free survival (39.9%+/- 6.2%) or overall survival (41.6%+/- 6.1%) at 8 years when compared with previous studies using less intensive regimens. Our results suggest that alternative therapies are needed to improve cure rates for pediatric patients with relapsed leukemia. C1 [Kelly, Michael E.; Camitta, Bruce] Med Coll Wisconsin, Div Pediat Hematol Oncol Bone Marrow Transplant, Milwaukee, WI 53226 USA. [Abshire, Thomas] BloodCtr Wisconsin, Inst Med Sci, Milwaukee, WI USA. [Lu, Xiaomin; Devidas, Meenakshi] Univ Florida, Dept Biostat, Gainesville, FL USA. [Sandler, Eric] Nemours Childrens Clin, Dept Pediat Oncol & Hematol, Jacksonville, FL USA. [Billett, Amy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Homans, Alan] Univ Vermont, Dept Pediat Hematol Oncol, Burlington, VT USA. [Buchanan, George] Univ Texas SW Med Ctr Dallas, Dept Pediat Hematol Oncol, Dallas, TX 75390 USA. [Bernstein, Mark L.] IWK Hlth Ctr, Halifax, NS, Canada. RP Kelly, ME (reprint author), Med Coll Wisconsin, Div Pediat Hematol Oncol Bone Marrow Transplant, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM mekelly@mcw.edu FU NIH [CA30969, CA29139, CA98543, CA98413] FX Supported by grants: CA30969, CA29139, CA98543, CA98413 from NIH. NR 19 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD OCT PY 2013 VL 35 IS 7 BP 509 EP 513 DI 10.1097/MPH.0b013e31829f3235 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 228VS UT WOS:000325220400018 PM 23887024 ER PT J AU Chemerinski, E Triebwasser, J Roussos, P Siever, LJ AF Chemerinski, Eran Triebwasser, Joseph Roussos, Panos Siever, Larry J. TI SCHIZOTYPAL PERSONALITY DISORDER SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID EVENT-RELATED POTENTIALS; CARD SORTING TEST; SCHIZOPHRENIA SPECTRUM DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; AUDITORY WORKING-MEMORY; PURSUIT EYE-MOVEMENTS; FRONTAL-LOBE FUNCTION; DSM-III; PREPULSE INHIBITION; ROSCOMMON FAMILY AB Early phenomenological descriptions of schizophrenia have acknowledged the existence of milder schizophrenia spectrum disorders characterized by the presence of attenuated symptoms typically present in chronic schizophrenia. The investigation of the schizophrenia spectrum disorders offers an opportunity to elucidate the pathophysiological mechanisms giving rise to schizophrenia. Differences and similarities between subjects with schizotypal personality disorder (SPD), the prototypical schizophrenia personality disorder, and chronic schizophrenia have been investigated with genetic, neurochemical, imaging, and pharmacological techniques. Patients with SPD and the more severely ill patients with chronic schizophrenia share cognitive, social, and attentional deficits hypothesized to result from common neurodevelopmentally based cortical temporal and prefrontal pathology. However, these deficits are milder in SPD patients due to their capacity to recruit other related brain regions to compensate for dysfunctional areas. Individuals with SPD are also less vulnerable to psychosis due to the presence of protective factors mitigating subcortical DA hyperactivity. Given the documented close relationship to other schizophrenic disorders, SPD will be included in the psychosis section of DSM-5 as a schizophrenia spectrum disorder as well as in the personality disorder section. C1 [Chemerinski, Eran; Triebwasser, Joseph; Roussos, Panos; Siever, Larry J.] James J Peters VA Med Ctr, New York, NY USA. RP Siever, LJ (reprint author), Bronx VA Med Ctr OOMH, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM larry.siever@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 NR 227 TC 4 Z9 4 U1 4 U2 16 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD OCT PY 2013 VL 27 IS 5 BP 652 EP 679 PG 28 WC Psychiatry SC Psychiatry GA 226NU UT WOS:000325043900011 PM 22928856 ER PT J AU Merkow, RP Bentrem, DJ Cohen, ME Paruch, JL Weber, SM Ko, CY Bilimoria, KY AF Merkow, Ryan P. Bentrem, David J. Cohen, Mark E. Paruch, Jennifer L. Weber, Sharon M. Ko, Clifford Y. Bilimoria, Karl Y. TI Effect of Cancer Surgery Complexity on Short-Term Outcomes, Risk Predictions, and Hospital Comparisons SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 8th Annual Academic Surgical Congress CY FEB 05-07, 2013 CL New Orleans, LA SP Assoc Acad Surg, Soc Univ Surg ID QUALITY IMPROVEMENT PROGRAM; PATIENT SAFETY; MODELS; ADJUSTMENT; VARIABLES; CARE AB BACKGROUND: Concern exists that oncologic surgical complexity is not adequately captured by the primary procedure code alone. Our objectives were to characterize the association between secondary procedures and 30-day outcomes, evaluate the effect of surgical complexity on risk predictions, and assess the influence of surgical complexity on hospital-quality comparisons. STUDY DESIGN: Patients who underwent colon, rectal, or pancreatic resection for cancer (2007-2011) were identified from theAmerican College of Surgeons NSQIP. Complexity was assessed by creating categorical complexity variables using secondary procedure codes and using total work relative value units. Regression methods were used to evaluate surgical complexity and hospital-quality comparisons. RESULTS: Patients had at least one secondary procedure documented in 48.0% of colon, 55.5% of rectal, and 63.1% of pancreatic cases. Surgical complexity variables were associated with worse outcomes across nearly all complications assessed. For example, serious morbidity was increased after an index colon resection with a synchronous liver resection (odds ratio = 1.39; 95% CI, 1.10-1.76) and a pancreatic resection with vascular reconstruction (odds ratio = 1.21; 95% CI, 1.01-1.45). Based on discrimination improvement indices and the likelihood ratio test, model-based predictions were enhanced with the addition of secondary surgical complexity variables, as well as total work relative value units, for nearly all procedures and outcomes assessed. Models that included total work relative value units had similar or marginally better discrimination compared with models with secondary procedure categories. Hospital performance did not change substantially after complexity adjustment. CONCLUSIONS: Surgical complexity adjustment is feasible and improves risk estimation of 30-day postoperative outcomes for colon, rectal, and pancreatic resections for cancer. Oncology-specific risk-adjustment models should include complexity adjustment using secondary procedure codes. (C) 2013 by the American College of Surgeons C1 [Merkow, Ryan P.; Cohen, Mark E.; Paruch, Jennifer L.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Feinberg Sch Med, Evanston, IL 60208 USA. [Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Northwestern Inst Comparat Effectiveness Res Onco, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Merkow, Ryan P.; Paruch, Jennifer L.] Univ Chicago, Dept Surg, Pritzker Sch Med, Chicago, IL 60637 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA. [Weber, Sharon M.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Fl, Chicago, IL 60611 USA. EM RMerkow@facs.org NR 23 TC 19 Z9 19 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2013 VL 217 IS 4 BP 685 EP 693 DI 10.1016/j.jamcollsurg.2013.05.015 PG 9 WC Surgery SC Surgery GA 227YR UT WOS:000325152100017 PM 23830986 ER PT J AU Sepucha, K Feibelmann, S Chang, Y Clay, CF Kearing, SA Tomek, I Yang, T Katz, JN AF Sepucha, Karen Feibelmann, Sandra Chang, Yuchiao Clay, Catharine F. Kearing, Stephen A. Tomek, Ivan Yang, Theresa Katz, Jeffrey N. TI Factors Associated with the Quality of Patients' Surgical Decisions for Treatment of Hip and Knee Osteoarthritis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID FORM HEALTH SURVEY; REPLACEMENT SURGERY; ARTHRITIS; OUTCOMES; AID; ARTHROPLASTY; DISPARITIES; KNOWLEDGE; IMPROVE; CHOICE AB BACKGROUND: Shared decision making requires informing patients and ensuring that treatment decisions reflect their goals. It is not clear to what extent this happens for patients considering total joint replacement (TJR) for hip or knee osteoarthritis. STUDY DESIGN: We conducted a cross-sectional mail survey of osteoarthritis patients at 4 sites, who made a decision about TJR. The survey measured knowledge and goals, the decision making process, decision confidence, and decision regret. Decision quality was defined as the percentage of patients who had high knowledge scores and received treatments that matched their goals. Multivariable regression models examined factors associated with knowledge and decision quality. RESULTS: There were 382 patients who participated (78.6% response rate). Mean knowledge score was 61% (SD 20.7%). In multivariate linear regression, higher education, having TJR, and site were associated with higher knowledge. Many patients (73%) received treatments that matched their goals. Thirty-one percent of patients met our definition for high decision quality. Higher decision making process scores, higher quality of life scores, and site were associated with higher decision quality. Patients who had high decision quality had less regret (73.1% vs 58.5%, p = 0.007) and greater confidence (9.0 [SD 1.6] vs 8.2 [SD 2.3] out of 10, p < 0.001). CONCLUSIONS: A third of patients who recently made a decision about osteoarthritis treatment met both criteria for a high quality decision. Controlling for treatment, patients reporting more involvement in the decision making process, higher quality of life, and being seen at a site that uses decision aids were associated with higher decision quality. (C) 2013 by the American College of Surgeons C1 [Sepucha, Karen; Feibelmann, Sandra; Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Internal Med, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Clay, Catharine F.; Kearing, Stephen A.] Dartmouth Hitchcock Med Ctr, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03766 USA. [Tomek, Ivan] Dartmouth Hitchcock Med Ctr, Dept Orthoped Surg, Lebanon, NH 03766 USA. [Yang, Theresa] Albany Med Coll, Albany, NY 12208 USA. RP Sepucha, K (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ksepucha@partners.org FU Informed Medical Decisions Foundation FX Dr Sepucha receives a salary as principal investigator for Informed Medical Decisions Foundation and Dr Kearing receives grant support as a research associate for Informed Medical Decisions Foundation. Supported by 2 grants (1 to Massachusetts General Hospital and 1 to Dartmouth Hitchcock Medical Center) from the Informed Medical Decisions Foundation. NR 24 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2013 VL 217 IS 4 BP 694 EP 701 DI 10.1016/j.jamcollsurg.2013.06.002 PG 8 WC Surgery SC Surgery GA 227YR UT WOS:000325152100018 PM 23891070 ER PT J AU Parikh, SA French, CA Costello, BA Marks, RS Dronca, RS Nerby, CL Roden, AC Peddareddigari, VG Hilton, J Shapiro, GI Molina, JR AF Parikh, Sameer A. French, Christopher A. Costello, Brian A. Marks, Randolph S. Dronca, Roxana S. Nerby, Craig L. Roden, Anja C. Peddareddigari, Vijay G. Hilton, John Shapiro, Geoffrey I. Molina, Julian R. TI NUT Midline Carcinoma An Aggressive Intrathoracic Neoplasm SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Poorly differentiated neoplasm; bromodomain containing 4 nuclear protein in testis; Epigenetics; Bromodomain and extra terminal inhibitor; Histone deacetylase inhibitors ID REARRANGEMENT; TRACT; TUMOR AB Nuclear protein in testis (NUT) midline carcinoma (NMC) is a poorly differentiated squamous cell carcinoma that is characterized by a balanced translocation between chromosomes 15 and 19 [t(15;19)(q14;p13.1)]. This genetic aberration results in the fusion of the NUT gene on chromosome 15 to the bromodomain containing 4 (BRD4) gene on chromosome 19. The resultant BRD4-NUT fusion oncogene leads to global hypoacetylation and transcriptional repression of genes required for differentiation. Although it was first reported in 1991 by Kubonishi et al., awareness of this condition remains low and the diagnosis is overlooked initially in a number of patients. A 36-year-old man complained of cough and right-sided chest pain for 3 weeks before presentation. Imaging studies revealed a right hilar mass, and a bronchoscopic biopsy was consistent with an aggressive poorly differentiated neoplasm. A combination of cisplatin, ifosfamide, and etoposide was administered for two cycles without any improvement. A repeat core biopsy showed focal squamous differentiation; and given the clinical presentation along with the histologic features, NMC was considered in the differential diagnosis. Immunohistochemical staining for NUT was positive, and dual-color break-apart fluorescence in situ hybridization demonstrated BRD4-NUT rearrangement, thereby confirming a diagnosis of NMC. Our patient was subsequently enrolled on a phase 1 clinical trial of a novel, orally bioavailable bromodomain and extra terminal inhibitor, GSK525762 (NCT01587703). This report illustrates the challenges in diagnosing this rare malignancy, and highlights new treatment options for these patients. C1 [Parikh, Sameer A.; Costello, Brian A.; Marks, Randolph S.; Dronca, Roxana S.; Molina, Julian R.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [French, Christopher A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nerby, Craig L.; Roden, Anja C.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Peddareddigari, Vijay G.] GlaxoSmithKline, Philadelphia, PA USA. [Hilton, John; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Parikh, SA (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM parikh.sameer@mayo.edu FU Synergene Therapeutics FX Dr. Costello is a member of the Data Safety and Monitoring Board for a phase 1 trial sponsored by Synergene Therapeutics and has received financial support for the same. Dr. Peddareddigari is currently employed by GlaxoSmithKline and owns stock in the company. The other authors declare no conflict of interest. NR 13 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2013 VL 8 IS 10 BP 1335 EP 1338 DI 10.1097/JTO.0b013e3182a00f41 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 222SL UT WOS:000324751300018 PM 24457244 ER PT J AU Dillon, ST Bhasin, MK Feng, XX Koh, DW Daoud, SS AF Dillon, Simon T. Bhasin, Manoj K. Feng, Xiaoxing Koh, David W. Daoud, Sayed S. TI Quantitative proteomic analysis in HCV-induced HCC reveals sets of proteins with potential significance for racial disparity SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Hepatocellular carcinoma; Hepatitis C; Tissue proteomics; Isobaric tags for relative and absolute quantification (iTRAQ); Cancer racial disparity ID CHRONIC HEPATITIS-C; VIRUS CORE PROTEIN; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; ALPHA-FETOPROTEIN; AFRICAN-AMERICANS; CANCER; EXPRESSION; INFECTION; CELLS AB Background: The incidence and mortality of hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) is higher in African Americans (AA) than other racial/ethnic groups in the U.S., but the reasons for this disparity are unknown. There is an urgent need for the discovery of novel molecular signatures for HCV disease progression to understand the underlying biological basis for this cancer rate disparity to improve the clinical outcome. Methods: We performed differential proteomics with isobaric labeling tags for relative and absolute quantitation (iTRAQ) and MS/MS analysis to identify proteins differentially expressed in cirrhotic (CIR) and HCC as compared to normal tissues of Caucasian American (CA) patients. The raw data were analyzed using the ProteinPilot v3.0. Searches were performed against all known sequences populating the Swiss-Prot, Refseq, and TrEMBL databases. Quality control analyses were accomplished using pairwise correlation plots, boxplots, principal component analysis, and unsupervised hierarchical clustering. Supervised analysis was carried out to identify differentially expressed proteins. Candidates were validated in independent cohorts of CA and AA tissues by qRT-PCR or Western blotting. Results: A total of 238 unique proteins were identified. Of those, around 15% were differentially expressed between normal, CIR & HCC groups. Target validation demonstrates racially distinct alteration in the expression of certain proteins. For example, the mRNA expression levels of transferrin (TF) were 2 and18-fold higher in CIR and HCC in AA as compared to CA. Similarly; the expression of Apolipoprotein A1 (APOA1) was 7-fold higher in HCC of AA. This increase was mirrored in the protein expression levels. Interestingly, the level of hepatocyte nuclear factor4 alpha (HNF4 alpha) protein was down regulated in AA, whereas repression of transcription is seen more in CA compared to AA. These data suggest that racial disparities in HCC could be a consequence of differential dysregulation of HNF4 alpha transcriptional activity. Conclusion: This study identifies novel molecular signatures in HCV-induced HCC using iTRAQ-based tissue proteomics. The proteins identified will further enhance a molecular explanation to the biochemical mechanism(s) that may play a role in HCC racial disparities. C1 [Dillon, Simon T.; Bhasin, Manoj K.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Feng, Xiaoxing; Koh, David W.; Daoud, Sayed S.] Washington State Univ, Dept Pharmaceut Sci, Pullman, WA 99164 USA. RP Daoud, SS (reprint author), Washington State Univ, Dept Pharmaceut Sci, Pullman, WA 99164 USA. EM daoud@wsu.edu NR 60 TC 8 Z9 8 U1 0 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 1 PY 2013 VL 11 AR 239 DI 10.1186/1479-5876-11-239 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 228YZ UT WOS:000325229400001 PM 24283668 ER PT J AU Ramanan, B Gupta, PK Sundaram, A Gupta, H Johanning, JM Lynch, TG MacTaggart, JN Pipinos, II AF Ramanan, Bala Gupta, Prateek K. Sundaram, Abhishek Gupta, Himani Johanning, Jason M. Lynch, Thomas G. MacTaggart, Jason N. Pipinos, Iraklis I. TI Development of a risk index for prediction of mortality after open aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SURGICAL CARE; ADJUSTMENT; SURGERY; QUALITY; SCORE AB Objective: Open infrarenal abdominal aortic aneurysm (oAAA) repair is associated with significant morbidity and mortality. Although there has been a shift toward endovascular repair, many patients continue to undergo an open repair due to anatomic considerations. Tools currently existing for estimation of periprocedural risk in patients undergoing open aortic surgery have certain limitations. The objective of this study was to develop a risk index to estimate the risk of 30-day perioperative mortality after elective oAAA repair. Methods: Patients who underwent elective oAAA repair (n = 2845) were identified from the American College of Surgeons' 2007 to 2009 National Surgical Quality Improvement Program (NSQIP), a prospective database maintained at >250 centers. Univariable and multivariable analyses were performed to evaluate risk factors associated with 30-day mortality after oAAA repair and a risk index was developed. Results: The 30-day mortality after oAAA repair was 3.3%. Multivariable analysis identified six preoperative predictors of mortality, and a risk index was created by assigning weighted points to each predictor using the beta-coefficients from the regression analysis. The predictors included dyspnea (at rest: 8 points; on moderate exertion: 2 points; none: 0 points), history of peripheral arterial disease requiring revascularization or amputation (3 points), age >65 years (3 points), preoperative creatinine >1.5 mg/dL (2 points), female gender (2 points), and platelets <150,000/mm(3) or >350,000/mm3 (2 points). Patients were classified as low (<7%), intermediate (7%-15%), and high (>15%) risk for 30-day mortality based on a total point score of <8, 8 to 11, and >11, respectively. There were 2508 patients (88.2%) patients in the low-risk category, 278 (9.8%) in the intermediate-risk category, and 59 (2.1%) in the high-risk category. Conclusions: This risk index has excellent predictive ability for mortality after oAAA repair and awaits validation in subsequent studies. It is anticipated to aid patients and surgeons in informed patient consent, preoperative risk assessment, and optimization. C1 [Ramanan, Bala; Sundaram, Abhishek] Creighton Univ, Dept Surg, Omaha, NE 68178 USA. [Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA. [Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Johanning, Jason M.; MacTaggart, Jason N.; Pipinos, Iraklis I.] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68198 USA. [Johanning, Jason M.; MacTaggart, Jason N.; Pipinos, Iraklis I.] VA Nebraska & Western Iowa Hlth Care Syst, Omaha, NE USA. [Lynch, Thomas G.] Vet Hlth Adm, Washington, DC USA. RP Pipinos, II (reprint author), Univ Nebraska Med Ctr, Dept Surg, Div Gen Surg, 985182 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ipipinos@unmc.edu FU National Institutes of Health [R01-AG-034995]; American Vascular Association; Charles and Mary Heider Fund for Excellence in Vascular Surgery FX This study was partly supported National Institutes of Health Grant R01-AG-034995, the William J. von Liebig Award by the American Vascular Association, and the Charles and Mary Heider Fund for Excellence in Vascular Surgery. NR 15 TC 14 Z9 14 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2013 VL 58 IS 4 BP 871 EP 878 DI 10.1016/j.jvs.2013.03.024 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 227RS UT WOS:000325132100002 PM 23676190 ER PT J AU Baril, DT Patel, VI Judelson, DR Goodney, PP McPhee, JT Hevelone, ND Cronenwett, JL Schanzer, A AF Baril, Donald T. Patel, Virendra I. Judelson, Dejah R. Goodney, Philip P. McPhee, James T. Hevelone, Nathanael D. Cronenwett, Jack L. Schanzer, Andres CA Vasc Study Grp New England TI Outcomes of lower extremity bypass performed for acute limb ischemia SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PROSPECTIVE RANDOMIZED-TRIAL; NATIVE ARTERY OCCLUSIONS; SURGICAL REVASCULARIZATION; INFRAINGUINAL BYPASS; INITIAL TREATMENT; VASCULAR-SURGERY; TIME TRENDS; THROMBOLYSIS; MORTALITY; SURVIVAL AB Objective: Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. Methods: All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Results: Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function, and respiratory complications. Patients who underwent lower extremity bypass for acute limb ischemia had no difference in rates of graft occlusion (18.1% vs 18.5%; P = .77), but did have significantly higher rates of limb loss (22.4% vs 9.7%; P < .0001) and mortality (20.9% vs 13.1%; P < .0001) at 1 year. On multivariable analysis, acute limb ischemia was an independent predictor of both major amputation (hazard ratio, 2.16; confidence interval, 1.38-3.40; P = .001) and mortality (hazard ratio, 1.41; confidence interval, 1.09-1.83; P = .009) at 1 year. Conclusions: Patients who present with acute limb ischemia represent a less medically optimized subgroup within the population of patients undergoing lower extremity bypass. These patients may be expected to have more complex operations followed by increased rates of perioperative adverse events. Additionally, despite equivalent graft patency rates, patients undergoing lower extremity bypass for acute ischemia have significantly higher rates of major amputation and mortality at 1 year. C1 [Baril, Donald T.; Judelson, Dejah R.; Schanzer, Andres] Univ Massachusetts, Med Ctr, Worcester, MA 01655 USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodney, Philip P.; Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [McPhee, James T.] Boston Med Ctr, Boston, MA USA. [Hevelone, Nathanael D.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Baril, DT (reprint author), Univ Massachusetts, Sch Med, Div Vasc & Endovasc Surg, 55 Lake Ave N, Worcester, MA 01655 USA. EM donald.baril@umassmemorial.org FU NHLBI NIH HHS [K08 HL105676] NR 29 TC 19 Z9 22 U1 0 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2013 VL 58 IS 4 BP 949 EP 956 DI 10.1016/j.jvs.2013.04.036 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 227RS UT WOS:000325132100014 PM 23714364 ER PT J AU Sobel, M Moreno, KI Yagi, M Kohler, TR Tang, GL Clowes, AW Zhou, XHA Eugenio, E AF Sobel, Michael Moreno, Katherine I. Yagi, Mayumi Kohler, Ted R. Tang, Gale L. Clowes, Alexander W. Zhou, Xiao-Hua A. Eugenio, Evercita TI Low levels of a natural IgM antibody are associated with vein graft stenosis and failure SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID OXIDATION-SPECIFIC EPITOPES; REDUCES ATHEROSCLEROSIS; PROTECTIVE FACTORS; IMMUNE-MODULATION; PHOSPHORYLCHOLINE; BYPASS; SURVEILLANCE; INFLAMMATION; IDENTIFICATION; MULTICENTER AB Background: All humans have natural, protective antibodies directed against phosphorylcholine (PC) epitopes, a common inflammatory danger signal appearing at sites of cell injury, oxidative stress, and on bacterial capsules. In large human cohorts, low levels of anti-PC IgM were associated with a significantly increased risk of stroke or myocardial infarction. However, it is not known if these antibodies protect against the premature closure of arterial reconstructions. Methods: A prospective, observational study of patients undergoing elective, infrainguinal, autogenous vein bypasses for atherosclerotic occlusive disease of the legs was conducted. Clinical data were recorded prospectively, and preoperative levels of anti-PC IgM measured with the CVDefine kit from Athera Biotechnologies (Solna, Sweden). The principal clinical end point was the loss of primary patency (loss of graft flow, or any intervention for stenosis). Patients were followed regularly by duplex ultrasound at 1, 3, 6, 12, 18 months, and yearly thereafter. Results: Fifty-six patients were studied, for an average of 1.3 years. Indications for surgery were claudication (33.9%), ischemic rest pain (17.9%), and ischemia with ulceration or gangrene (48.2%). Seventeen (30.4%) patients experienced loss of primary patency (10 graft occlusions, seven surgical or endovascular revisions of graft stenoses). Kaplan-Meier survival analysis showed that the quartile of patients with the lowest anti-PC IgM levels had significantly worse primary graft patency (log-rank test, P = .0085). Uni- and multivariate Cox proportional hazards analysis revealed that the preoperative anti-PC IgM level was an important predictor of graft failure. Patients with IgM values in the lowest quartile had a 3.6-fold increased risk of graft failure (95% confidence interval: 1.1-12.1), even after accounting for other significant clinical or technical factors such as indication for surgery, site of distal anastomosis, or vein graft diameter. Conclusions: A naturally occurring IgM antibody directed against the proinflammatory epitope PC may be protective against vein graft stenosis and failure, through anti-inflammatory mechanisms. Measurement of this antibody may be a useful prognostic indicator, although larger studies of more diverse populations will be needed to confirm these results. The biological actions of anti-PC IgM suggest it may be useful in developing immunotherapies to improve bypass longevity. C1 [Sobel, Michael; Moreno, Katherine I.; Yagi, Mayumi; Kohler, Ted R.; Tang, Gale L.; Clowes, Alexander W.] VA Puget Sound Hlth Care Syst, Div Vasc Surg, Seattle, WA USA. [Sobel, Michael; Moreno, Katherine I.; Yagi, Mayumi; Kohler, Ted R.; Tang, Gale L.; Clowes, Alexander W.] Univ Washington, Seattle, WA 98195 USA. [Zhou, Xiao-Hua A.; Eugenio, Evercita] VA Puget Sound Hlth Care Syst, Northwest Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Zhou, Xiao-Hua A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Sobel, M (reprint author), VA Puget Sound Hlth Care Syst S112, Div Vasc Surg, 1660 Columbian Way S, Seattle, WA 98108 USA. EM sobelm@uw.edu FU Department of Veterans Affairs, Veterans Health Administration, Merit Review Agency; Research Career Scientist Award [RCS 05-196]; National Institutes of Health [T32 HL007828, R01HL030946] FX This work was supported by grants from the Department of Veterans Affairs, Veterans Health Administration, Merit Review Agency (M.S.) and Research Career Scientist Award (RCS 05-196 - X.H.Z.); and National Institutes of Health T32 HL007828 and R01HL030946 (A.C., M.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 40 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2013 VL 58 IS 4 BP 997 EP + DI 10.1016/j.jvs.2013.04.042 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 227RS UT WOS:000325132100020 PM 23856610 ER PT J AU Gray, KM Saladin, ME Baker, NL McClure, EA Hartwell, KJ Carpenter, MJ AF Gray, Kevin M. Saladin, Michael E. Baker, Nathaniel L. McClure, Erin A. Hartwell, Karen J. Carpenter, Matthew J. TI Varenicline Versus Nicotine Patch for Smoking Cessation in Women: Efficacy Findings from a 4-Week Double-blind Trial SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Gray, Kevin M.; Saladin, Michael E.; Baker, Nathaniel L.; McClure, Erin A.; Hartwell, Karen J.; Carpenter, Matthew J.] Med Univ S Carolina, Charleston, SC USA. [Hartwell, Karen J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT 1 PY 2013 VL 22 IS 10 BP 904 EP 904 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 227TD UT WOS:000325136500099 ER PT J AU Sgroi, DC Sestak, I Cuzick, J Zhang, Y Schnabel, CA Schroeder, B Erlander, MG Dunbier, A Sidhu, K Lopez-Knowles, E Goss, PE Dowsett, M AF Sgroi, Dennis C. Sestak, Ivana Cuzick, Jack Zhang, Yi Schnabel, Catherine A. Schroeder, Brock Erlander, Mark G. Dunbier, Anita Sidhu, Kally Lopez-Knowles, Elena Goss, Paul E. Dowsett, Mitch TI Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population SO LANCET ONCOLOGY LA English DT Article ID MOLECULAR GRADE INDEX; POSTMENOPAUSAL PATIENTS; ADJUVANT TREATMENT; PROGNOSTIC-FACTORS; HORMONAL-THERAPY; STOCKHOLM TRIAL; CLINICAL-TRIAL; ATAC TRIAL; FOLLOW-UP; TAMOXIFEN AB Background Biomarkers to improve the risk-benefi t of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immuno histochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (NO) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial. Methods In this prospective comparison study, we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived. We did BCI analysis in matched samples with sufficient residual RNA using two BCI models-cubic (BCI-C) and linear (BCI-L)-using previously validated cutoffs. We assessed prognostic ability of BCI for distant recurrence over 10 years (the primary endpoint) and compared it with that of the 21-gene recurrence score and IHC4. We also tested the ability of the assays to predict early (0-5 years) and late (5-10 years) distant recurrence. To assess the ability of the biomarkers to predict recurrence beyond standard clinicopathological variables, we calculated the change in the likelihood-ratio. chi(2) (LR-Delta chi(2)) from Cox proportional hazards models. Findings Suitable tissue was available from 665 patients with oestrogen-receptor-positive, NO breast cancer for BCI analysis. The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups (p< 0 . 0001) with 6 . 8% (95% CI 4 . 4-10 . 0) of patients in the low-risk group, 17 . 3% (12 . 0-24 . 7) in the intermediate group, and 22 . 2% (15 . 3-31 . 5) in the high-risk group having distant recurrence. The secondary analysis showed that BCI-L was a much stronger predictor for overall (0-10 year) distant recurrence compared with BCI-C (interquartile HR 2 . 30 [95% CI 1 . 62-3 . 27]; LR-Delta chi(2) = 22 . 69; p< 0 . 0001). When compared with BCI-L, the 21-gene recurrence score was less predictive (HR 1 . 48 [95% CI 1 . 22-1 . 78]; LR-Delta chi 2 = 13 . 68; p= 0 . 0002) and IHC4 was similar (HR 1 . 69 [95% CI 1 . 51-2 . 56]; LR-Delta chi(2) = 22 . 83; p< 0 . 0001). All further analyses were done with the BCI-L model. In a multivariable analysis, all assays had signifi cant prognostic ability for early distant recurrence (BCI-L HR 2 . 77 [95% CI 1 . 63-4 . 70], LR-Delta chi(2) = 15 . 42, p< 0 . 0001; 21-gene recurrence score HR 1 . 80 [1 . 42-2 . 29], LR Delta chi(2) = 18 . 48, p< 0 . 0001; IHC4 HR 2 . 90 [2 . 01-4 . 18], LR-Delta chi(2) = 29 . 14, p< 0 . 0001); however, only BCI-L was signifi cant for late distant recurrence (BCI-L HR 1 . 95 [95% CI 1 . 22-3 . 14], LR-Delta chi(2) = 7 . 97, p= 0 . 0048; 21-gene recurrence score HR 1 . 13 [0 . 82-1 . 56], LR-Delta chi(2) = 0 . 48, p= 0 . 47; IHC4 HR 1 . 30 [0 . 88-1 . 94], LR-Delta chi(2) = 1 . 59, p= 0 . 20). Interpretation BCI-L was the only signifi cant prognostic test for risk of both early and late distant recurrence and identified two risk populations for each timeframe. It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy. C1 [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. [Sgroi, Dennis C.; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. [Sestak, Ivana; Cuzick, Jack] Queen Mary Univ, Ctr Canc Prevent, London, England. [Zhang, Yi; Schnabel, Catherine A.; Schroeder, Brock; Erlander, Mark G.] bioTheranostics, San Diego, CA USA. [Dunbier, Anita; Sidhu, Kally; Lopez-Knowles, Elena; Dowsett, Mitch] Royal Marsden Hosp, Breakthrough Breast Canc Ctr, London SW3 6JJ, England. [Dowsett, Mitch] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. [Dowsett, Mitch] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England. [Dunbier, Anita] Univ Otago, Dept Biochem, Dunedin, New Zealand. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. EM dsgroi@partners.org OI Sestak, Ivana/0000-0001-6999-2851 FU Avon Foundation; National Institutes of Health; Breast Cancer Foundation; US Department of Defense Breast Cancer Research Program; Breakthrough Breast Cancer through the Mary- Jean Mitchell Green Foundation; AstraZeneca; Cancer Research UK; National Institute for Health Research Biomedical Research Centre at the Royal Marsden (London, UK) FX Funding Avon Foundation, National Institutes of Health, Breast Cancer Foundation, US Department of Defense Breast Cancer Research Program, Susan G Komen for the Cure, Breakthrough Breast Cancer through the Mary- Jean Mitchell Green Foundation, AstraZeneca, Cancer Research UK, and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden (London, UK). NR 34 TC 90 Z9 90 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2013 VL 14 IS 11 BP 1067 EP 1076 DI 10.1016/S1470-2045(13)70387-5 PG 10 WC Oncology SC Oncology GA 227EI UT WOS:000325091900039 PM 24035531 ER PT J AU Dimopoulos, M Siegel, DS Lonial, S Qi, JY Hajek, R Facon, T Rosinol, L Williams, C Blacklock, H Goldschmidt, H Hungria, V Spencer, A Palumbo, A Graef, T Eid, JE Houp, J Sun, L Vuocolo, S Anderson, KC AF Dimopoulos, Meletios Siegel, David S. Lonial, Sagar Qi, Junyuan Hajek, Roman Facon, Thierry Rosinol, Laura Williams, Catherine Blacklock, Hilary Goldschmidt, Hartmut Hungria, Vania Spencer, Andrew Palumbo, Antonio Graef, Thorsten Eid, Joseph E. Houp, Jennifer Sun, Linda Vuocolo, Scott Anderson, Kenneth C. TI Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study SO LANCET ONCOLOGY LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; PHASE-I; CANCER; CARFILZOMIB; PROTEASOME; TRIAL AB Background We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. Methods In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (= 18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1: 1) using an interactive voice response system to receive 21 day cycles of bortezomib (1 . 3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage = 2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or = 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials. gov, number 00773747. Findings Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7 . 63 months (95% CI 6 . 87-8 . 40) in the vorinostat group and 6 . 83 months (5 . 67-7 . 73) in the placebo group (hazard ratio [HR] 0 . 77, 95% CI 0 . 64-0 . 94; p= 0 . 0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most common grade 3-4 adverse events were thrombocytopenia (143 [45%] patients in the vorinostat group vs 77 [24%] patients in the placebo group), neutropenia (89 [28%] vs 80 [25%]), and anaemia (53 [17%] vs 40 [13%]). Interpretation Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo, the clinical relevance of the diff erence in PFS between the two groups is not clear. Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity. C1 [Dimopoulos, Meletios] Univ Athens, Dept Clin Therapeut, Athens, Greece. [Siegel, David S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Lonial, Sagar] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Qi, Junyuan] Chinese Acad Med Sci, Inst Hematol, Lymphocyte Dis Ctr, Tianjin, Peoples R China. [Qi, Junyuan] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Qi, Junyuan] Peking Union Med Coll, Tianjin, Peoples R China. [Hajek, Roman] Univ Hosp Brno, Brno, Czech Republic. [Hajek, Roman] Univ Ostrava, CZ-70103 Ostrava, Czech Republic. [Facon, Thierry] Ctr Hosp Reg & Univ Lille, Hop Huriez, Serv Malad Sang, F-59037 Lille, France. [Rosinol, Laura] Hosp Clin Barcelona, Barcelona, Spain. [Williams, Catherine] Univ Nottingham Hosp, Nottingham NG7 2UH, England. [Blacklock, Hilary] Middlemore Hosp, Auckland 6, New Zealand. [Goldschmidt, Hartmut] Univ Kliniken Heidelberg, Heidelberg, Germany. [Hungria, Vania] Santa Casa Sao Paulo, Sao Paulo, Brazil. [Spencer, Andrew] Monash Univ, Alfred Hosp, Melbourne, Vic 3181, Australia. [Palumbo, Antonio] Univ Turin, Div Hematol, Turin, Italy. [Graef, Thorsten; Eid, Joseph E.; Houp, Jennifer; Sun, Linda; Vuocolo, Scott] Merck, Whitehouse Stn, NJ USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dimopoulos, M (reprint author), Univ Athens, Dept Clin Therapeut, Athens, Greece. EM mdimop@med.uoa.gr RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 FU Merck FX Funding Merck. NR 19 TC 85 Z9 88 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2013 VL 14 IS 11 BP 1129 EP 1140 DI 10.1016/S1470-2045(13)70398-X PG 12 WC Oncology SC Oncology GA 227EI UT WOS:000325091900046 PM 24055414 ER PT J AU van Kruchten, M de Vries, EGE Brown, M de Vries, EFJ Glaudemans, AWJM Dierckx, RAJO Schroder, CP Hospers, GAP AF van Kruchten, Michel de Vries, Elisabeth G. E. Brown, Myles de Vries, Erik F. J. Glaudemans, Andor W. J. M. Dierckx, Rudi A. J. O. Schroder, Carolien P. Hospers, Geke A. P. TI PET imaging of oestrogen receptors in patients with breast cancer SO LANCET ONCOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; HORMONE-BINDING GLOBULIN; IN-VIVO; FLUORINE-18-LABELED ESTROGENS; IMMUNOHISTOCHEMICAL ANALYSIS; METABOLIC FLARE; UTERINE-TUMORS; FES PET; TAMOXIFEN; ALPHA AB Oestrogen receptors are overexpressed in around 70% of all breast cancers, and are a target for endocrine therapy. These receptors can be visualised on PET with use of 16 alpha-[F-18]-fluoro-17 beta-oestradiol (F-18-FES) as a tracer. Compared with biopsy, which enables assessment of individual sites, whole-body F-18-FES-PET enables quantification of oestrogen-receptor expression in all metastases. In several studies, measurement of tumour protein expression in oestrogen receptors by F-18-FES-PET, concurrent with biopsy, detected oestrogen-receptor-positive tumour lesions with a sensitivity of 84% and specificity of 98%. Roughly 45% of patients with metastatic breast cancer have discordant oestrogen-receptor expression across lesions (ie, F-18-FES-positive and F-18-FES-negative metastases). Low tumour F-18-FES uptake in metastases can predict failure of hormonal therapy in patients with oestrogen-receptor-positive primary tumours. Finally, F-18-FES-PET has shown that oestrogen-receptor binding capacity changes after intervention with hormonal drugs, but findings need to be confirmed. Factors other than oestrogen-receptor expression, including menopausal status and concomitant therapies, that can affect tumour F-18-FES uptake must be taken into account. C1 [van Kruchten, Michel; de Vries, Elisabeth G. E.; Schroder, Carolien P.; Hospers, Geke A. P.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands. [de Vries, Erik F. J.; Glaudemans, Andor W. J. M.; Dierckx, Rudi A. J. O.] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, Groningen, Netherlands. [Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. RP Hospers, GAP (reprint author), Univ Med Ctr Groningen, Dept Med Oncol, POB 30-001, NL-9700 RB Groningen, Netherlands. EM g.a.p.hospers@umcg.nl FU Dutch Cancer Society [RUG 2009-4529]; Centre for Translational Molecular Medicine-Mammary Carcinoma Molecular Imaging for Diagnosis and Therapeutics (CTMM - MAMMOTH) Project [03O-201] FX This research was supported by the Dutch Cancer Society (grant RUG 2009-4529) and the Centre for Translational Molecular Medicine-Mammary Carcinoma Molecular Imaging for Diagnosis and Therapeutics (CTMM - MAMMOTH) Project (grant 03O-201). We thank Esther van Straten for her assistance with designing figure 5. NR 85 TC 47 Z9 47 U1 4 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2013 VL 14 IS 11 BP E465 EP E475 PG 11 WC Oncology SC Oncology GA 227EI UT WOS:000325091900022 PM 24079874 ER PT J AU Wei, CC Adappa, ND Cohen, NA AF Wei, Calvin C. Adappa, Nithin D. Cohen, Noam A. TI Use of Topical Nasal Therapies in the Management of Chronic Rhinosinusitis SO LARYNGOSCOPE LA English DT Review DE Chronic rhinosinusitis; antifungals; antibiotics; antimicrobials; nasal irrigations; topical therapy ID ENDOSCOPIC SINUS SURGERY; RANDOMIZED CONTROLLED-TRIAL; FLUTICASONE PROPIONATE; DOUBLE-BLIND; MOMETASONE FUROATE; AMPHOTERICIN-B; INTRANASAL BUDESONIDE; STAPHYLOCOCCUS-AUREUS; ANTIFUNGAL TREATMENT; SINONASAL SYMPTOMS AB Objectives/HypothesisTo determine whether the use of topical nasal therapies with saline alone and in combination with antibiotics, antifungals, or corticosteroids is effective in the treatment of patients with chronic rhinosinusitis (CRS). Data SourcesA systematic literature search was performed utilizing the MEDLINE database (1966 to May 2012), EMBASE database (1980 to May 2012), and the Cochrane Central Register of Controlled Trials. Review MethodsElectronic databases were searched by three otolaryngologists. Studies on five major categories of topical nasal therapies searched included saline (hypotonic, isotonic and hypertonic); topical antibiotics, topical steroids, and topical antifungals were obtained. Randomized controlled trials and meta-analyses of randomized controlled trials were included. ResultsSixteen randomized controlled trials were identified examining topical saline (hypertonic or isotonic) in CRS patients. Two randomized controlled trials were found studying the effect of topical antibiotics in patients with CRS. Four randomized controlled trials were identified studying topical antifungal treatment for CRS. Twenty-five randomized controlled trials were found studying topical steroids in CRS patients. ConclusionA high aggregate quality of evidence supports the effectiveness of saline irrigations in treating CRS. There is insufficient evidence to support a clear benefit of topical antibiotics in patients with chronic rhinosinusitis. Topical antifungal therapies have not been shown to be significantly different in efficacy than saline controls on CRS outcomes. Topical steroids are beneficial in the treatment of CRS with nasal polyps, but have not been shown to be effective in CRS without nasal polyps. Laryngoscope, 123:2347-2359, 2013 C1 [Wei, Calvin C.] St Lukes Roosevelt Hosp, Dept Otolaryngol Head & Neck Surg, New York, NY 10025 USA. [Adappa, Nithin D.; Cohen, Noam A.] Univ Penn, Sch Med, Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Sch Med, Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM Noam.Cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 72 TC 22 Z9 22 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2013 VL 123 IS 10 BP 2347 EP 2359 DI 10.1002/lary.24066 PG 13 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 227EC UT WOS:000325091100006 PM 23553558 ER PT J AU Mahboubi, H Salibian, AA Wu, EC Patel, MS Armstrong, WB AF Mahboubi, Hossein Salibian, Ara A. Wu, Edward C. Patel, Madhukar S. Armstrong, William B. TI The Role and Utilization of Electronic Medical Records in Ambulatory Otolaryngology SO LARYNGOSCOPE LA English DT Article DE Electronic medical record; electronic health record; otolaryngology; outpatient practice; National Ambulatory Medical Care Survey; ambulatory surgery ID HEALTH RECORDS; INFORMATICS COMMITTEE; DECISION-SUPPORT; MEANINGFUL USE; CARE; QUALITY; PHYSICIANS; HEAD; RECOMMENDATIONS; INTERVENTIONS AB Objectives/HypothesisTo estimate the usage of electronic medical records (EMRs) in ambulatory otolaryngology and to compare the usage trends between otolaryngologists and physicians in other specialties. Study DesignCross-sectional analysis of data taken from the National Ambulatory Medical Care Survey (NAMCS). MethodsThe 2005 to 2010 NAMCS datasets were analyzed for whether storage of patient records in otolaryngology practices were completely electronic, partly electronic, or paper based. The trend of EMR utilization in the studied period was compared between otolaryngology and other specialties. Furthermore, the usage of different EMR functions (e.g., ordering tests) was also evaluated. ResultsThe proportion of otolaryngology practices with complete or partial EMR usage increased from 27.0% in 2005 to 2006, to 48.5% in 2009 to 2010 (P<.001), and was projected to increase to 80.3% in 2015 to 2016. Otolaryngologists had variable usage of different functions of EMRs. Neither the overall use of EMRs nor their different functions were statistically different between otolaryngologists and other specialists. Further exploration of data revealed that 34.0% of otolaryngologists intended to install new EMR systems within the following years. Finally, 39.9% of otolaryngologists had plans to apply for Medicare or Medicaid incentive payments, of which 92.3% expected to start meaningful use in 2011. ConclusionsThe increasing utilization of EMRs in ambulatory otolaryngology is an important marker of progress in compliance with health care reform. Despite this upward trend, however, <50% of ambulatory offices had adopted EMRs in 2009 to 2010, and it remains to be seen how the field will adapt to the evolving challenge of EMR adoption and implementation. Laryngoscope, 123:2418-2422, 2013 C1 [Mahboubi, Hossein; Salibian, Ara A.; Armstrong, William B.] Univ Calif Irvine, Dept Otolaryngol Head & Neck Surg, Irvine, CA USA. [Wu, Edward C.] Univ Calif Los Angeles, Los Angeles Med Ctr, Dept Head & Neck Surg, Los Angeles, CA USA. [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Armstrong, WB (reprint author), Univ Calif Irvine, Dept Otolaryngol Head & Neck Surg, 101 City Dr S,Bldg 56,Ste 500, Orange, CA 92868 USA. EM wbarmstr@uci.edu OI Mahboubi, Hossein/0000-0003-4418-5302; Kuan, Edward/0000-0003-3475-0718 NR 24 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2013 VL 123 IS 10 BP 2418 EP 2422 DI 10.1002/lary.24104 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 227EC UT WOS:000325091100018 PM 23619936 ER PT J AU Roberts, DS Lin, HW Bhattacharyya, N AF Roberts, Daniel S. Lin, Harrison W. Bhattacharyya, Neil TI Health Care Practice Patterns for Balance Disorders in the Elderly SO LARYNGOSCOPE LA English DT Article DE Balance disorders; elderly; dizziness; vertigo; geriatric ID NATIONALLY REPRESENTATIVE SAMPLE; DIZZINESS; POPULATION; PREVALENCE; MANAGEMENT; DIAGNOSES; COMMUNITY AB Objectives/HypothesisCharacterize health care practice patterns for balance disorders in the elderly. Study DesignCross-sectional analysis of national health care survey. MethodsBalance disorder cases in patients aged 65 years were extracted from the 2008 National Health Interview Survey. Records were analyzed for health professionals seen, diagnostic testing ordered, diagnoses given, and treatments offered. Relationships between diagnostic success, imaging studies, and specialty providers seen were compared. ResultsAmong 7.020.22 million elderly persons reporting a balance problem, 50.0% (3.440.16 million) saw a health professional, and 35.8% saw 3 providers; 59.6% of elderly patients reported a diagnosed cause for the balance problem. The most common causes were medication side effects (11.3%), inner ear infection (11.0%), heart disease (8.6%), and loose ear crystals (7.9%). Imaging studies had been obtained in 56.7% (2.00 +/- 0.11 million cases). Among 24.3% of patients receiving some form of treatment, 61.7% had been taking prescription medication, most commonly diuretic agents (36.5%), anxiolytic agents (25.1%), and meclizine (21.4%). Seeing an otolaryngologist or neurologist was associated with a higher but similar rate of diagnostic imaging studies (70.1%, P=.029 and 78.5%, P<.001). However, obtaining an imaging study was not associated with a diagnosed cause of the balance disorder (61.5% with imaging vs. 56.9% without, P=.265). ConclusionsDespite a high prevalence of balance problems in the elderly, a significant proportion do not come to a clear diagnosis. There is a noteworthy rate of prescription medication utilization in this population. Given an increasingly aging population, attention needs to be given to balance problems in the elderly to optimize diagnosis and health care utilization. Level of Evidence2b Laryngoscope, 123:2539-2543, 2013 C1 [Roberts, Daniel S.; Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Roberts, Daniel S.; Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Dept Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. RP Roberts, DS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Roberts@meei.harvard.edu FU Triological Society through the William W. Montgomery, MD Resident Research Award from the Eastern Section FX The authors thank the Triological Society, which supported this work through the William W. Montgomery, MD Resident Research Award from the Eastern Section. NR 17 TC 13 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2013 VL 123 IS 10 BP 2539 EP 2543 DI 10.1002/lary.24087 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 227EC UT WOS:000325091100038 PM 23720236 ER PT J AU Abou-Nassar, KE Vanderplas, A Friedberg, JW Abel, GA Niland, J Rodriguez, MA Czuczman, MS Millenson, M Crosby, A Gordon, LI Zelenetz, AD Kaminski, M Lacasce, AS AF Abou-Nassar, Karim E. Vanderplas, Ann Friedberg, Jonathan W. Abel, Gregory A. Niland, Joyce Rodriguez, Maria A. Czuczman, Myron S. Millenson, Michael Crosby, Allison Gordon, Leo I. Zelenetz, Andrew D. Kaminski, Mark Lacasce, Ann S. TI Patterns of use of 18-fluoro-2-deoxy-D-glucose positron emission tomography for initial staging of grade 1-2 follicular lymphoma and its impact on initial treatment strategy in the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes database SO LEUKEMIA & LYMPHOMA LA English DT Article DE Follicular lymphoma; FDG-PET imaging; staging ID TERM-FOLLOW-UP; PET; RADIOTHERAPY; THERAPY; CLASSIFICATION; MANAGEMENT; F-18-FDG; INDOLENT; NHL; CT AB We describe the patterns of use of 18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the initial staging of patients with newly diagnosed grade 1-2 follicular lymphoma (FL) and its potential impact on treatment. Data were obtained from the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes database. Patients who presented between 1 January 2001 and 30 September 2009 with newly diagnosed grade 1-2 FL, with at least 6 months of follow-up, were included. We identified 953 eligible patients and 532 (56%) underwent FDG-PET as part of initial staging. Among patients who underwent FDG-PET for initial staging, 438 (82%) received early treatment compared to 259 (61.5%) of those staged without FDG-PET (p < 0.0001). Of all patients with stage I FL (n = 100), 47% were treated with radiotherapy (RT) alone, and the choice of initial treatment strategy for stage I FL did not vary significantly by use of FDG-PET (p = 0.22). The use of FDG-PET for staging of FL is widespread and is associated with a greater proportion of patients receiving early therapy. Given the widespread use and high cost of FDG-PET, its clinical utility in stage I FL should be further evaluated. C1 [Abou-Nassar, Karim E.] Ctr Sante & Serv Sociaux Gatineau, Dept Hematol, Gatineau, PQ, Canada. [Niland, Joyce] City Hope Natl Med Ctr, Data Coordinating Ctr, Duarte, CA 91010 USA. [Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Abel, Gregory A.; Crosby, Allison; Lacasce, Ann S.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Rodriguez, Maria A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kaminski, Mark] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Lacasce, AS (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM Ann_lacasce@dfci.harvard.edu FU National Comprehensive Cancer Network FX This work was supported by the National Comprehensive Cancer Network. NR 24 TC 5 Z9 5 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2013 VL 54 IS 10 BP 2155 EP 2162 DI 10.3109/10428194.2013.770151 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 220MX UT WOS:000324589800014 PM 23343180 ER PT J AU Ghobrial, IM AF Ghobrial, Irene M. TI Revisiting treatment paradigms in high-risk smoldering multiple myeloma: out with the old, in with the new? SO LEUKEMIA & LYMPHOMA LA English DT Letter ID LENALIDOMIDE; PROGRESSION; CRITERIA C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu NR 14 TC 3 Z9 3 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2013 VL 54 IS 10 BP 2328 EP 2330 DI 10.3109/10428194.2013.788699 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 220MX UT WOS:000324589800047 PM 23540345 ER PT J AU Huang, C Bilgin, A Barr, T Altbach, MI AF Huang, Chuan Bilgin, Ali Barr, Tomoe Altbach, Maria I. TI T-2 Relaxometry with Indirect Echo Compensation from Highly Undersampled Data SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE T-2 estimation; relaxometry; FSE; stimulated echo; indirect echo; principal component analysis; non-180 degrees refocusing pulse ID TISSUE CHARACTERIZATION; MRI; RECONSTRUCTION; SEQUENCE; BRAIN; LIVER; HEART; TIMES AB PurposeTo develop an algorithm for fast and accurate T-2 estimation from highly undersampled multi-echo spin-echo data. MethodsThe algorithm combines a model-based reconstruction with a signal decay based on the slice-resolved extended phase graph (SEPG) model with the goal of reconstructing T-2 maps from highly undersampled radial multi-echo spin-echo data with indirect echo compensation. To avoid problems associated with the nonlinearity of the SEPG model, principal component decomposition is used to linearize the signal model. The proposed CUrve Reconstruction via principal component-based Linearization with Indirect Echo compensation (CURLIE) algorithm is used to estimate T-2 curves from highly undersampled data. T-2 maps are obtained by fitting the curves to the SEPG model. ResultsResults on phantoms showed T-2 biases (1.9% to 18.4%) when indirect echoes are not taken into account. The T-2 biases were reduced (< 3.2%) when the CURLIE reconstruction was performed along with SEPG fitting even for high degrees of undersampling (4% sampled). Experiments in vivo for brain, liver, and heart followed the same trend as the phantoms. ConclusionThe CURLIE reconstruction combined with SEPG fitting enables accurate T-2 estimation from highly undersampled multi-echo spin-echo radial data thus, yielding a fast T-2 mapping method without errors caused by indirect echoes. Magn Reson Med, 70:1026-1037, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Huang, Chuan] Univ Arizona, Dept Math, Tucson, AZ 85724 USA. [Huang, Chuan] Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Radiol Sci, Boston, MA 02114 USA. [Bilgin, Ali] Univ Arizona, Dept Elect & Comp Engn, Tucson, AZ 85724 USA. [Bilgin, Ali; Barr, Tomoe] Univ Arizona, Dept Biomed Engn, Tucson, AZ 85724 USA. [Altbach, Maria I.] Univ Arizona, Dept Med Imaging, Tucson, AZ 85724 USA. RP Altbach, MI (reprint author), Univ Arizona, Dept Med Imaging, Tucson, AZ 85724 USA. EM maltbach@email.arizona.edu OI Huang, Chuan/0000-0001-6052-0663 FU NIH [HL085385] FX Grant sponsor: NIH; Grant number: HL085385. NR 31 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2013 VL 70 IS 4 BP 1026 EP 1037 DI 10.1002/mrm.24540 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 227TB UT WOS:000325136300014 PM 23165796 ER PT J AU Maciejewski, ML Wang, V Burgess, JF Bryson, CL Perkins, M Liu, CF AF Maciejewski, Matthew L. Wang, Virginia Burgess, James F., Jr. Bryson, Chris L. Perkins, Mark Liu, Chuan-Fen TI The Continuity and Quality of Primary Care SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE continuity of care; VA reliance; quality of care; diabetes; veterans; Medicare ID RECOMMENDED AMBULATORY-CARE; PHYSICIAN VISIT CONTINUITY; AFFAIRS HEALTH-CARE; OUTPATIENT CLINICS; DIABETES CARE; MEDICAL-CARE; VETERANS; SERVICES; SYSTEM; PERFORMANCE AB Patients who have access to different health care systems, such as Medicare-eligible veterans, may obtain services in either or both health systems. We examined whether quality of diabetes care was associated with care continuity or veterans' usual source of primary care in a retrospective cohort study of 1,867 Medicare-eligible veterans with diabetes in 2001 to 2004. Underprovision of quality of diabetes care was more common than overprovision. In adjusted analyses, veterans who relied only on Medicare fee-for-service (FFS) for primary care were more likely to be underprovided HbA1c testing than veterans who relied only on Veteran Affairs (VA) for primary care. Dual users of VA and Medicare FFS primary care were significantly more likely to be overprovided HbA1c and microalbumin testing than VA-only users. VA and Medicare providers may need to coordinate more effectively to ensure appropriate diabetes care to Medicare-eligible veterans, because VA reliance was a stronger predictor than care continuity. C1 [Maciejewski, Matthew L.; Wang, Virginia] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Maciejewski, Matthew L.; Wang, Virginia] Duke Univ, Med Ctr, Durham, NC USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Boston, MA 02215 USA. [Bryson, Chris L.; Perkins, Mark; Liu, Chuan-Fen] US Dept Vet Affairs, Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Bryson, Chris L.; Liu, Chuan-Fen] Univ Washington, Seattle, WA 98195 USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. EM matthew.maciejewski@va.gov FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 04-292]; Research Career Scientist award from the Department of Veterans Affairs [RCS 10-391] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, Project Number IIR 04-292. Dr. Maciejewski was also supported by a Research Career Scientist award from the Department of Veterans Affairs (RCS 10-391). NR 35 TC 0 Z9 0 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD OCT PY 2013 VL 70 IS 5 BP 497 EP 513 DI 10.1177/1077558713495454 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 227UQ UT WOS:000325141100003 PM 23868082 ER PT J AU Woo, SB Cashman, EC Lerman, MA AF Woo, Sook-Bin Cashman, Emma C. Lerman, Mark A. TI Human papillomavirus-associated oral intraepithelial neoplasia SO MODERN PATHOLOGY LA English DT Article DE HPV apoptotic oral epithelial dysplasia; koilocytic dysplasia ID FOCAL EPITHELIAL HYPERPLASIA; SQUAMOUS-CELL CARCINOMA; BOWENOID PAPULOSIS; OROPHARYNGEAL CANCER; PREMALIGNANT LESIONS; MALIGNANT LESIONS; DYSPLASIA; HPV; EXPRESSION; P16 AB This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer. C1 [Woo, Sook-Bin; Lerman, Mark A.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Woo, Sook-Bin; Lerman, Mark A.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA. [Woo, Sook-Bin; Lerman, Mark A.] Strata Pathol Serv, Cambridge, MA USA. [Cashman, Emma C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cashman, Emma C.] Harvard Univ, Sch Med, Boston, MA USA. RP Lerman, MA (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1 Brigham Circle,Suite 3-028, Boston, MA 02120 USA. EM mark_lerman@hsdm.harvard.edu NR 44 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2013 VL 26 IS 10 BP 1288 EP 1297 DI 10.1038/modpathol.2013.70 PG 10 WC Pathology SC Pathology GA 228TR UT WOS:000325214000002 PM 23599160 ER PT J AU He, WL Cheville, JC Sadow, PM Gopalan, A Fine, SW Al-Ahmadie, HA Chen, YB Oliva, E Russo, P Reuter, VE Tickoo, SK AF He, Wenlei Cheville, John C. Sadow, Peter M. Gopalan, Anuradha Fine, Samson W. Al-Ahmadie, Hikmat A. Chen, Ying-Bei Oliva, Esther Russo, Paul Reuter, Victor E. Tickoo, Satish K. TI Epithelioid angiomyolipoma of the kidney: pathological features and clinical outcome in a series of consecutively resected tumors SO MODERN PATHOLOGY LA English DT Article DE epithelioid angiomyolipoma; PEComa; renal angiomyolipoma ID TUBEROUS SCLEROSIS; RENAL ANGIOMYOLIPOMA; VARIANT; TSC2; TRANSFORMATION; PECOMAS; LESIONS AB The 2004 World Health Organization classification of tumors defines epithelioid angiomyolipoma of kidney as a potentially malignant mesenchymal neoplasm with reported metastasis in approximately one-third of the cases. However, this conclusion was based primarily on individual case reports and small retrospective series. More recently reported larger series have shown varying results. We reviewed 437 consecutive renal angiomyolipomas with primary resection at three tertiary-care institutions with high nephrectomy volumes. Only tumors showing >80% epithelioid histology were included in this study. Tumors resected elsewhere and reviewed in consultation were not included. Twenty of these 437 (4.6%) were classified as epithelioid angiomyolipoma. The female to male ratio was 11: 9, mean age 49.7 (range, 30-80) years, and mean tumor size 8.7 (range, 1-25) cm. Microscopic tumor necrosis was present in 10 (50%) tumors and mitotic activity (range, <1-5/10 high power fields) in 8 (40%); atypical mitoses were seen in only 1 (5%) tumor. Pleomorphic ganglion-like or multinucleated giant cells were seen in 18 (90%) tumors. With a mean follow-up of 82.5 (range, 1-356) months, seventeen patients were alive with no-evidence-of-disease at the time of last follow-up; two patients died of unrelated causes with no-evidence-of-disease, and one patient (5%) developed distant metastases. Our data, based on consecutively resected angiomyolipomas with long clinical follow-up, suggests that epithelioid angiomyolipomas constitute a small proportion of all angiomyolipomas, and the rate of aggressive behavior among epithelioid angiomyolipomas, even when showing morphologic features previously reported to portend aggressive clinical behavior, is very low. C1 [He, Wenlei; Gopalan, Anuradha; Fine, Samson W.; Al-Ahmadie, Hikmat A.; Chen, Ying-Bei; Reuter, Victor E.; Tickoo, Satish K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Cheville, John C.] Mayo Clin, Dept Pathol, Rochester, MN USA. [Sadow, Peter M.; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Russo, Paul] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10065 USA. RP Tickoo, SK (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA. EM tickoos@mskcc.org OI Al-Ahmadie, Hikmat/0000-0002-2938-6627; Chen, Ying-Bei/0000-0001-5207-3648 NR 28 TC 15 Z9 20 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2013 VL 26 IS 10 BP 1355 EP 1364 DI 10.1038/modpathol.2013.72 PG 10 WC Pathology SC Pathology GA 228TR UT WOS:000325214000009 PM 23599151 ER PT J AU Zack, TI Schumacher, SE Carter, SL Cherniack, AD Saksena, G Tabak, B Lawrence, MS Zhang, CZ Wala, J Mermel, CH Sougnez, C Gabriel, SB Hernandez, B Shen, H Laird, PW Getz, G Meyerson, M Beroukhim, R AF Zack, Travis I. Schumacher, Steven E. Carter, Scott L. Cherniack, Andrew D. Saksena, Gordon Tabak, Barbara Lawrence, Michael S. Zhang, Cheng-Zhong Wala, Jeremiah Mermel, Craig H. Sougnez, Carrie Gabriel, Stacey B. Hernandez, Bryan Shen, Hui Laird, Peter W. Getz, Gad Meyerson, Matthew Beroukhim, Rameen TI Pan-cancer patterns of somatic copy number alteration SO NATURE GENETICS LA English DT Article ID CIRCULAR BINARY SEGMENTATION; ACUTE MYELOID-LEUKEMIA; LONG NONCODING RNAS; BREAST-CANCER; CHROMOSOMAL-ABERRATIONS; LYMPHOBLASTIC-LEUKEMIA; FRAGILE SITES; LUNG-CANCER; CGH DATA; GENOME AB Determining how somatic copy number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. Whole-genome doubling, observed in 37% of cancers, was associated with higher rates of every other type of SCNA, TP53 mutations, CCNE1 amplifications and alterations of the PPP2R complex. SCNAs that were internal to chromosomes tended to be shorter than telomere-bounded SCNAs, suggesting different mechanisms underlying their generation. Significantly recurrent focal SCNAs were observed in 140 regions, including 102 without known oncogene or tumor suppressor gene targets and 50 with significantly mutated genes. Amplified regions without known oncogenes were enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs were anticorrelated, and these regions tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer-related SCNAs. C1 [Zack, Travis I.; Schumacher, Steven E.; Carter, Scott L.; Cherniack, Andrew D.; Saksena, Gordon; Tabak, Barbara; Lawrence, Michael S.; Zhang, Cheng-Zhong; Wala, Jeremiah; Mermel, Craig H.; Sougnez, Carrie; Gabriel, Stacey B.; Hernandez, Bryan; Getz, Gad; Meyerson, Matthew; Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Zack, Travis I.; Schumacher, Steven E.; Wala, Jeremiah; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zack, Travis I.] Harvard Univ, Biophys Program, Boston, MA 02115 USA. [Wala, Jeremiah] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Wala, Jeremiah] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Shen, Hui; Laird, Peter W.] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA USA. [Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Beroukhim, R (reprint author), Broad Inst, Cambridge, MA USA. EM rameen_beroukhim@dfci.harvard.edu RI Schumacher, Steven/E-9821-2013; Laird, Peter/G-8683-2012 OI Schumacher, Steven/0000-0002-6819-5647; FU Genome Characterization Center of the US National Institutes of Health [U24CA143867]; Genome Data Analysis Center of the US National Institutes of Health [U24CA143845]; US NIH/National Cancer Institute [U54CA143798, U54HG003067, U24CA143882]; V Foundation; Pediatric Low-Grade Astrocytoma Foundation FX We gratefully acknowledge contributions from the TCGA Research Network and its TCGA Pan-Cancer Analysis Working Group (contributing consortium members are listed in the Supplementary Note). We thank A. Shehata, P. Bandopadhayay, W. Gibson, R. Ferrer and P. Horowitz for their help and comments during construction of the manuscript. This work was conducted as part of The Cancer Genome Atlas Research Network, with funding from grants U24CA143867 (Genome Characterization Center: M. M., R. B. and G. G.) and U24CA143845 (Genome Data Analysis Center: G. G. and M. M.) of the US National Institutes of Health. Additional support was from US NIH/National Cancer Institute grants U54CA143798 (R. B.), U54HG003067 (S. B. G.) and U24CA143882 (P. W. L.) and from the V Foundation and Pediatric Low-Grade Astrocytoma Foundation (R. B.). NR 78 TC 328 Z9 331 U1 4 U2 51 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2013 VL 45 IS 10 SI SI BP 1134 EP U257 DI 10.1038/ng.2760 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 225UQ UT WOS:000324989600008 PM 24071852 ER PT J AU Ripke, S O'Dushlaine, C Chambert, K Moran, JL Kahler, AK Akterin, S Bergen, SE Collins, AL Crowley, JJ Fromer, M Kim, Y Lee, SH Magnusson, PKE Sanchez, N Stahl, EA Williams, S Wray, NR Xia, K Bettella, F Borglum, AD Bulik-Sullivan, BK Cormican, P Craddock, N de Leeuw, C Durmishi, N Gill, M Golimbet, V Hamshere, ML Holmans, P Hougaard, DM Kendler, KS Lin, K Morris, DW Mors, O Mortensen, PB Neale, BM O'Neill, FA Owen, MJ Milovancevic, MP Posthuma, D Powell, J Richards, AL Riley, BP Ruderfer, D Rujescu, D Sigurdsson, E Silagadze, T Smit, AB Stefansson, H Steinberg, S Suvisaari, J Tosato, S Verhage, M Walters, JT Bramon, E Corvin, AP O'Donovan, MC Stefansson, K Scolnick, E Purcell, S McCarroll, SA Sklar, P Hultman, CM Sullivan, PF AF Ripke, Stephan O'Dushlaine, Colm Chambert, Kimberly Moran, Jennifer L. Kaehler, Anna K. Akterin, Susanne Bergen, Sarah E. Collins, Ann L. Crowley, James J. Fromer, Menachem Kim, Yunjung Lee, Sang Hong Magnusson, Patrik K. E. Sanchez, Nick Stahl, Eli A. Williams, Stephanie Wray, Naomi R. Xia, Kai Bettella, Francesco Borglum, Anders D. Bulik-Sullivan, Brendan K. Cormican, Paul Craddock, Nick de Leeuw, Christiaan Durmishi, Naser Gill, Michael Golimbet, Vera Hamshere, Marian L. Holmans, Peter Hougaard, David M. Kendler, Kenneth S. Lin, Kuang Morris, Derek W. Mors, Ole Mortensen, Preben B. Neale, Benjamin M. O'Neill, Francis A. Owen, Michael J. Milovancevic, Milica Pejovic Posthuma, Danielle Powell, John Richards, Alexander L. Riley, Brien P. Ruderfer, Douglas Rujescu, Dan Sigurdsson, Engilbert Silagadze, Teimuraz Smit, August B. Stefansson, Hreinn Steinberg, Stacy Suvisaari, Jaana Tosato, Sarah Verhage, Matthijs Walters, James T. Bramon, Elvira Corvin, Aiden P. O'Donovan, Michael C. Stefansson, Kari Scolnick, Edward Purcell, Shaun McCarroll, Steven A. Sklar, Pamela Hultman, Christina M. Sullivan, Patrick F. CA Multictr Genetic Studies Schizophr Psychosis Endophenotypes Int Conso Wellcome Trust Case Control Consor TI Genome-wide association analysis identifies 13 new risk loci for schizophrenia SO NATURE GENETICS LA English DT Article ID DEPENDENT CALCIUM-CHANNELS; BIPOLAR DISORDER; COMMON VARIANTS; GENE-EXPRESSION; DE-NOVO; PSYCHIATRIC-DISORDERS; RHEUMATOID-ARTHRITIS; SPATIAL MEMORY; DISEASE; METAANALYSIS AB Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder. C1 [Ripke, Stephan; Fromer, Menachem; Bulik-Sullivan, Brendan K.; Neale, Benjamin M.; Purcell, Shaun] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L.; Fromer, Menachem; Sanchez, Nick; Neale, Benjamin M.; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Kaehler, Anna K.; Collins, Ann L.; Crowley, James J.; Kim, Yunjung; Williams, Stephanie; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. [Kaehler, Anna K.; Akterin, Susanne; Bergen, Sarah E.; Magnusson, Patrik K. E.; Hultman, Christina M.; Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Kaehler, Anna K.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Fromer, Menachem; Stahl, Eli A.; Ruderfer, Douglas; Purcell, Shaun; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [Lee, Sang Hong; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Xia, Kai; Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Bettella, Francesco; Stefansson, Hreinn; Steinberg, Stacy; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Borglum, Anders D.] Aarhus Univ Hosp, Risskov, Denmark. [Borglum, Anders D.] Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark. [Borglum, Anders D.; Mors, Ole; Mortensen, Preben B.] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark. [Borglum, Anders D.; Mors, Ole; Mortensen, Preben B.] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark. [Cormican, Paul; Gill, Michael; Morris, Derek W.; Corvin, Aiden P.] Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland. [Craddock, Nick; Hamshere, Marian L.; Holmans, Peter; Owen, Michael J.; Richards, Alexander L.; Walters, James T.; O'Donovan, Michael C.] Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales. [de Leeuw, Christiaan; Posthuma, Danielle; Verhage, Matthijs] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands. [de Leeuw, Christiaan; Posthuma, Danielle; Verhage, Matthijs] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [de Leeuw, Christiaan] Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands. [Durmishi, Naser] Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia. [Gill, Michael; Morris, Derek W.; Corvin, Aiden P.] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Golimbet, Vera] Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia. [Hougaard, David M.] Statens Serum Inst, DK-2300 Copenhagen, Denmark. [Kendler, Kenneth S.; Riley, Brien P.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Kendler, Kenneth S.; Riley, Brien P.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Lin, Kuang; Powell, John; Bramon, Elvira] Kings Coll London, Inst Psychiat, London, England. [Mors, Ole] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark. [Mortensen, Preben B.] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark. [O'Neill, Francis A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Milovancevic, Milica Pejovic] Univ Belgrade, Fac Med, Belgrade, Serbia. [Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Powell, John] Kings Coll London, Dept Neurosci, London, England. [Riley, Brien P.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA. [Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany. [Rujescu, Dan] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Sigurdsson, Engilbert] Univ Iceland, Dept Psychiat, Reykjavik, Iceland. [Silagadze, Teimuraz] Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Rep of Georgia. [Smit, August B.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands. [Smit, August B.] Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands. [Suvisaari, Jaana] Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland. [Tosato, Sarah] Univ Verona, Sect Psychiat, I-37100 Verona, Italy. [Bramon, Elvira] UCL, Inst Cognit Neurosci, London, England. [Bramon, Elvira] UCL, Mental Hlth Sci Unit, London, England. [Purcell, Shaun] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. EM pfsulliv@med.unc.edu RI Mathew, Christopher/G-3434-2015; Ruderfer, Douglas/M-5795-2016; Wood, Nicholas/C-2505-2009; Magnusson, Patrik/C-4458-2017; Collier, David/D-1649-2011; Powell, John/G-4412-2011; Xia, Kai/B-7214-2014; Sigurdsson, Engilbert/D-2486-2014; Kahler, Anna/J-2874-2012; Deloukas, Panos/B-2922-2013; Jablensky, Assen/H-5116-2014; Lee, Sang Hong/A-2569-2011; Wray, Naomi/C-8639-2015; Holmans, Peter/F-4518-2015; Jankowski, Janusz/H-2706-2012; Blackwell, Jenefer/H-3015-2015; Mortensen, Preben/D-2358-2015 OI O'Neill, Francis Anthony/0000-0002-7531-7657; verhage, matthijs/0000-0002-6085-7503; Palmer, Colin/0000-0002-6415-6560; Trembath, Richard/0000-0003-0550-3400; Golimbet, Vera/0000-0002-9960-7114; Walshe, Muriel/0000-0001-6829-1105; murray, robin/0000-0003-0829-0519; Pirinen, Matti/0000-0002-1664-1350; McIntosh, Andrew/0000-0002-0198-4588; Morris, Derek/0000-0002-3413-570X; Hunt, Sarah/0000-0002-8350-1235; Gill, Michael/0000-0003-0206-5337; Moran, Jennifer/0000-0002-5664-4716; Gillman, Matthew/0000-0002-2340-6930; Walters, James/0000-0002-6980-4053; Plomin, Robert/0000-0002-0756-3629; Mathew, Christopher/0000-0003-4178-1838; Ruderfer, Douglas/0000-0002-2365-386X; Wood, Nicholas/0000-0002-9500-3348; Bergen, Sarah/0000-0002-5888-0034; Golimbet, Vera/0000-0002-0114-4300; Stefansson, Hreinn/0000-0002-9331-6666; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Crowley, James/0000-0001-9051-1557; Collier, David/0000-0003-4087-1559; Powell, John/0000-0001-6124-439X; Sigurdsson, Engilbert/0000-0001-9404-7982; Deloukas, Panos/0000-0001-9251-070X; Lee, Sang Hong/0000-0001-9701-2718; Wray, Naomi/0000-0001-7421-3357; Holmans, Peter/0000-0003-0870-9412; Jankowski, Janusz/0000-0003-2130-9181; Mortensen, Preben/0000-0002-5230-9865 FU NIMH [R01 MH077139, R01 MH095034]; Stanley Center for Psychiatric Research; Sylvan Herman Foundation; Friedman Brain Institute at the Mount Sinai School of Medicine; Karolinska Institutet, Karolinska University Hospital; Swedish Research Council; Swedish County Council; Soderstrom Konigska Foundation; Netherlands Scientific Organization [NWO 645-000-003]; European Union [HEALTH-F2-2009-223423]; Danish Strategic Research Council; H. Lundbeck A/S; Faculty of Health Sciences at Aarhus University; Lundbeck Foundation; Stanley Research Foundation; Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z] FX We are deeply grateful for the participation of all subjects contributing to this research and to the collection team that worked to recruit them: E. Flordal-Thelander, A.-B. Holmgren, M. Hallin, M. Lundin, A.-K. Sundberg, C. Pettersson, R. Satgunanthan-Dawoud, S. Hassellund, M. Radstrom, B. Ohlander, L. Nyren and I. Kizling. Funding support was provided by the NIMH (R01 MH077139 to P. F. S. and R01 MH095034 to P. S.), the Stanley Center for Psychiatric Research, the Sylvan Herman Foundation, the Friedman Brain Institute at the Mount Sinai School of Medicine, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Swedish County Council, the Soderstrom Konigska Foundation and the Netherlands Scientific Organization (NWO 645-000-003). SGENE was supported by European Union grant HEALTH-F2-2009-223423 (project PsychCNVs). The study of the Aarhus sample was supported by grants from the Danish Strategic Research Council, H. Lundbeck A/S, the Faculty of Health Sciences at Aarhus University, the Lundbeck Foundation and the Stanley Research Foundation. The Wellcome Trust Case Control Consortium 2 project collection was funded by the Wellcome Trust (085475/B/08/Z and 085475/Z/08/Z). The funders had no role in study design, execution or analysis or in manuscript preparation. NR 98 TC 493 Z9 494 U1 15 U2 164 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2013 VL 45 IS 10 SI SI BP 1150 EP U282 DI 10.1038/ng.2742 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 225UQ UT WOS:000324989600010 PM 23974872 ER PT J AU Farhat, MR Shapiro, BJ Kieser, KJ Sultana, R Jacobson, KR Victor, TC Warren, RM Streicher, EM Calver, A Sloutsky, A Kaur, D Posey, JE Plikaytis, B Oggioni, MR Gardy, JL Johnston, JC Rodrigues, M Tang, PKC Kato-Maeda, M Borowsky, ML Muddukrishna, B Kreiswirth, BN Kurepina, N Galagan, J Gagneux, S Birren, B Rubin, EJ Lander, ES Sabeti, PC Murray, M AF Farhat, Maha R. Shapiro, B. Jesse Kieser, Karen J. Sultana, Razvan Jacobson, Karen R. Victor, Thomas C. Warren, Robin M. Streicher, Elizabeth M. Calver, Alistair Sloutsky, Alex Kaur, Devinder Posey, Jamie E. Plikaytis, Bonnie Oggioni, Marco R. Gardy, Jennifer L. Johnston, James C. Rodrigues, Mabel Tang, Patrick K. C. Kato-Maeda, Midori Borowsky, Mark L. Muddukrishna, Bhavana Kreiswirth, Barry N. Kurepina, Natalia Galagan, James Gagneux, Sebastien Birren, Bruce Rubin, Eric J. Lander, Eric S. Sabeti, Pardis C. Murray, Megan TI Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis SO NATURE GENETICS LA English DT Article ID INTRINSIC MULTIDRUG-RESISTANCE; COMPENSATORY MUTATIONS; 2-COMPONENT SYSTEM; RIFAMPIN-RESISTANT; ESCHERICHIA-COLI; FITNESS; GENES; SUSCEPTIBILITY; ANTIBIOTICS; EXPRESSION AB M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly sequenced and 7 previously sequenced M. tuberculosis whole genomes, we identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains. By searching for convergent evolution-the independent fixation of mutations in the same nucleotide position or gene-we recovered 100% of a set of known resistance markers. We also found evidence of positive selection in an additional 39 genomic regions in resistant isolates. These regions encode components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways. Mutations in these regions could directly confer resistance or compensate for fitness costs associated with resistance. Functional genetic analysis of mutations in one gene, ponA1, demonstrated an in vitro growth advantage in the presence of the drug rifampicin. C1 [Farhat, Maha R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02114 USA. [Shapiro, B. Jesse; Galagan, James; Birren, Bruce; Lander, Eric S.; Sabeti, Pardis C.] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Shapiro, B. Jesse; Sabeti, Pardis C.] Harvard Univ, Fac Arts & Sci, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Shapiro, B. Jesse; Sabeti, Pardis C.] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Shapiro, B. Jesse] Univ Montreal, Dept Sci Biol, Montreal, PQ H3C 3J7, Canada. [Kieser, Karen J.; Rubin, Eric J.; Sabeti, Pardis C.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Sultana, Razvan] Dana Farber Canc Inst, Dept Bioinformat & Computat Biol, Boston, MA 02115 USA. [Jacobson, Karen R.] Boston Univ, Sch Med, Infect Dis Sect, Boston, MA 02118 USA. [Jacobson, Karen R.; Victor, Thomas C.; Warren, Robin M.; Streicher, Elizabeth M.] Univ Stellenbosch, Fac Med & Hlth Sci, Ctr Mol & Cellular Biol,Dept Sci & Technol,Div Mo, MRC,Natl Res Fdn Ctr Excellence Biomed IB Res, ZA-7505 Tygerberg, South Africa. [Calver, Alistair] Anglogold Ashanti Hlth West Vaal Hosp, Orkney, South Africa. [Sloutsky, Alex; Kaur, Devinder] Univ Massachusetts, Sch Med, Massachusetts Supranat TB Reference Lab, Boston, MA 02125 USA. [Posey, Jamie E.; Plikaytis, Bonnie] Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. [Oggioni, Marco R.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Gardy, Jennifer L.] British Columbia Ctr Dis Control, Communicable Dis Prevent & Control Serv, Vancouver, BC, Canada. [Johnston, James C.] British Columbia Ctr Dis Control, Clin Prevent Serv, Vancouver, BC, Canada. [Rodrigues, Mabel; Tang, Patrick K. C.] British Columbia Ctr Dis Control, Prov Hlth Serv Author Labs, Publ Hlth Microbiol & Reference Lab, Mycobacteriol TB Lab, Vancouver, BC, Canada. [Kato-Maeda, Midori] Univ Calif San Francisco, Div Pulm & Crit Care, San Francisco, CA 94143 USA. [Muddukrishna, Bhavana] Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. [Muddukrishna, Bhavana] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Kreiswirth, Barry N.; Kurepina, Natalia] State Univ New Jersey, Rutgers, Publ Hlth Res Inst TB Ctr, Newark, NJ USA. [Galagan, James] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Galagan, James] Boston Univ, Dept Microbiol, Boston, MA 02215 USA. [Galagan, James] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Gagneux, Sebastien] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Gagneux, Sebastien] Univ Basel, Basel, Switzerland. [Murray, Megan] Harvard Univ, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Farhat, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02114 USA. EM mrfarhat@partners.org; mmurray@hsph.harvard.edu RI Oggioni, Marco Rinaldo/K-3839-2016; OI Oggioni, Marco Rinaldo/0000-0003-4117-793X; Farhat, Maha/0000-0002-3871-5760; Shapiro, B. Jesse/0000-0001-6819-8699; Rubin, Eric/0000-0001-5120-962X; Streicher, Elizabeth/0000-0003-3901-1981; Jacobson, Karen/0000-0003-4239-3685; Tang, Patrick/0000-0003-1583-5484 FU Senior Ellison Foundation Award; National Institute of Allergy and Infectious Diseases [HHSN266200400001C]; Department of Pulmonary and Critical Care at Massachusetts General Hospital; Harvard MIDAS Center for Communicable Disease Dynamics; Packard Foundation; Swiss National Science Foundation [PP0033_119205] FX We thank the technical staff of the British Columbia Centre for Disease Control Public Health Microbiology and Reference Mycobacteriology Laboratory in Vancouver, M. Bosman from the National Health Laboratory Service in Cape Town and L. Fattorini from the Istituto Superiore di Sanita in Rome. This work was funded by a Senior Ellison Foundation Award (M. M.) and in part by a contact from the National Institute of Allergy and Infectious Diseases (HHSN266200400001C to B. B.), the Department of Pulmonary and Critical Care at Massachusetts General Hospital (M. R. F.), a postdoctoral fellowship from the Harvard MIDAS Center for Communicable Disease Dynamics (B.J.S.) and a Packard Foundation Fellowship (P. C. S.). S. G. was supported by the Swiss National Science Foundation (PP0033_119205). NR 45 TC 104 Z9 111 U1 6 U2 82 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2013 VL 45 IS 10 SI SI BP 1183 EP U320 DI 10.1038/ng.2747 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 225UQ UT WOS:000324989600014 PM 23995135 ER PT J AU Garris, C Pittet, MJ AF Garris, Christopher Pittet, Mikael J. TI Therapeutically reeducating macrophages to treat GBM SO NATURE MEDICINE LA English DT Editorial Material ID TUMOR-ASSOCIATED MACROPHAGES; KAPPA-B; POLARIZATION; PROGRESSION; CANCER C1 [Garris, Christopher; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Garris, Christopher] Harvard Univ, Sch Med, Grad Program Immunol, Boston, MA USA. RP Garris, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu NR 14 TC 6 Z9 7 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2013 VL 19 IS 10 BP 1207 EP 1208 DI 10.1038/nm.3355 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 232YW UT WOS:000325531700010 PM 24100977 ER PT J AU Kim, ND Luster, AD AF Kim, Nancy D. Luster, Andrew D. TI To B or not to B-that is the question for myocardial infarction SO NATURE MEDICINE LA English DT Editorial Material ID BONE-MARROW; MONOCYTE EMIGRATION; CELLS; CCR2 C1 [Kim, Nancy D.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA. RP Kim, ND (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA. EM aluster@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2013 VL 19 IS 10 BP 1208 EP 1210 DI 10.1038/nm.3367 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 232YW UT WOS:000325531700011 PM 24100978 ER PT J AU Pandey, GS Yanover, C Miller-Jenkins, LM Garfield, S Cole, SA Curran, JE Moses, EK Rydz, N Simhadri, V Kimchi-Sarfaty, C Lillicrap, D Viel, KR Przytycka, TM Pierce, GF Howard, TE Sauna, ZE AF Pandey, Gouri Shankar Yanover, Chen Miller-Jenkins, Lisa M. Garfield, Susan Cole, Shelley A. Curran, Joanne E. Moses, Eric K. Rydz, Natalia Simhadri, Vijaya Kimchi-Sarfaty, Chava Lillicrap, David Viel, Kevin R. Przytycka, Teresa M. Pierce, Glenn F. Howard, Tom E. Sauna, Zuben E. CA PATH Personalized Alternative TI Endogenous factor VIII synthesis from the intron 22-inverted F8 locus may modulate the immunogenicity of replacement therapy for hemophilia A SO NATURE MEDICINE LA English DT Article ID COAGULATION-FACTOR VIII; MONOCLONAL-ANTIBODIES; HUMAN-LIVER; INHIBITOR; ANTIGEN; HISTORY; GENE AB Neutralizing antibodies (inhibitors) to replacement factor VIII (FVIII, either plasma derived or recombinant) impair the effective management of hemophilia A1. Individuals with hemophilia A due to major deletions of the FVIII gene (F8) lack antigenically cross-reactive material in their plasma ("CRM-negative"), and the prevalence of inhibitors in these individuals may be as high as 90%. Conversely, individuals with hemophilia A caused by F8 missense mutations are CRM-positive, and their overall prevalence of inhibitors is < 10% (ref. 2). Individuals with the F8 intron 22 inversion (found in similar to 50% of individuals with severe hemophilia A) have been grouped with the former on the basis of their genetic defect and CRM-negative status. However, only similar to 20% of these individuals develop inhibitors3. Here we demonstrate that the levels of F8 mRNA and intracellular FVIII protein in B lymphoblastoid cells and liver biopsies from individuals with the intron 22 inversion are comparable to those in healthy controls. These results support the hypothesis that most individuals with the intron 22 inversion are tolerized to FVIII and thus do not develop inhibitors. Furthermore, we developed a new pharmacogenetic algorithm that permits the stratification of inhibitor risk for individuals and subpopulations by predicting the immunogenicity of replacement FVIII using, as input, the number of putative T cell epitopes in the infused protein and the competence of major histocompatibility complex class II molecules to present such epitopes. This algorithm showed statistically significant accuracy in predicting the presence of inhibitors in 25 unrelated individuals with the intron 22 inversion. C1 [Pandey, Gouri Shankar; Simhadri, Vijaya; Kimchi-Sarfaty, Chava; Sauna, Zuben E.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Hemostasis, Bethesda, MD 20892 USA. [Yanover, Chen] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Miller-Jenkins, Lisa M.] NCI, Lab Cell Biol, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Garfield, Susan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cole, Shelley A.; Curran, Joanne E.; Moses, Eric K.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Rydz, Natalia; Lillicrap, David] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada. [Viel, Kevin R.] Histonis, Atlanta, GA USA. [Przytycka, Teresa M.] Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD USA. [Pierce, Glenn F.] Biogen Idec Hemophilia, Waltham, MA USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Howard, Tom E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. RP Sauna, ZE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Hemostasis, Bethesda, MD 20892 USA. EM tom.howard@va.gov; zuben.sauna@fda.hhs.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU US National Institute of Allergy and Infectious Diseases Committee on Human Research [10-01178]; modernization of science program of the Center for Biologics Evaluation and Research, US Food and Drug Administration; National Heart, Lung and Blood Institute, National Institutes of Health [1RC2-HL101851, HL-71130, HL-72533)]; Bayer Healthcare Corporation; Bayer Hemophilia Awards Program; Baxter Healthcare Corporation; Clinical Translational Science Institute at the University of Southern California; Intramural Program of the US National Library of Medicine, NIH FX We would like to thank P. Matzinger, B. Golding, J. Lozier, D. Levin, M. Carcao, V. Blanchette, G. Rivard and V. La Terza for helpful comments and J. Sauna for help with the graphics. We thank S. V. Ambudkar (US National Cancer Institute) for the use of facilities, M. J. Lenardo and K. Shafer-Weaver (US National Institute of Allergy and Infectious Diseases) for the gift of the purified C2 domain of FVIII and P. Stock (University of California, San Francisco) for liver tissue samples. These samples were obtained under the University of California University-Wide AIDS Research Program (TP-99-SF-001) Committee on Human Research (H802423454) and the Solid Organ Transplantation in HIV: Multi-Site Study (AI052748) funded by the US National Institute of Allergy and Infectious Diseases Committee on Human Research (10-01178). Research conducted in the laboratory of Z. E. S. is funded by the modernization of science program of the Center for Biologics Evaluation and Research, US Food and Drug Administration. Research conducted in the laboratory of T. E. H. is funded by grants from the National Heart, Lung and Blood Institute, National Institutes of Health (1RC2-HL101851, HL-71130 and HL-72533), the Bayer Healthcare Corporation, Bayer Hemophilia Awards Program, Baxter Healthcare Corporation and the Clinical Translational Science Institute at the University of Southern California. The work of T. M. P. is fully supported by the Intramural Program of the US National Library of Medicine, NIH. NR 22 TC 27 Z9 27 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2013 VL 19 IS 10 BP 1318 EP + DI 10.1038/nm.3270 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 232YW UT WOS:000325531700032 PM 24037092 ER PT J AU Maeder, ML Linder, SJ Cascio, VM Fu, YF Ho, QH Joung, JK AF Maeder, Morgan L. Linder, Samantha J. Cascio, Vincent M. Fu, Yanfang Ho, Quan H. Joung, J. Keith TI CRISPR RNA-guided activation of endogenous human genes SO NATURE METHODS LA English DT Article ID EXPRESSION; SYSTEMS AB Short guide RNAs (gRNAs) can direct catalytically inactive CRISPR-associated 9 nuclease (dCas9) to repress endogenous genes in bacteria and human cells. Here we show that single or multiple gRNAs can direct dCas9 fused to a VP64 transcriptional activation domain to increase expression of endogenous human genes. This proof-of-principle work shows that clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems can target heterologous effector domains to endogenous sites in human cells. C1 [Maeder, Morgan L.; Linder, Samantha J.; Cascio, Vincent M.; Fu, Yanfang; Ho, Quan H.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Maeder, Morgan L.; Linder, Samantha J.; Cascio, Vincent M.; Fu, Yanfang; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Linder, Samantha J.; Cascio, Vincent M.; Fu, Yanfang; Ho, Quan H.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Fu, Yanfang; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. EM jjoung@partners.org FU US National Institutes of Health (NIH) [DP1 GM105378, NIH R01 NS073124, NIH P50 HG005550]; Defense Advanced Research Projects Agency (DARPA) [W911NF-11-2-0056]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award FX This work was supported by a US National Institutes of Health (NIH) Director's Pioneer Award DP1 GM105378, NIH R01 NS073124, NIH P50 HG005550, Defense Advanced Research Projects Agency (DARPA) W911NF-11-2-0056, and the Jim and Ann Orr Massachusetts General Hospital Research Scholar Award. We thank J.D. Sander (Massachusetts General Hospital) for providing plasmid pJDS246 and for helpful discussions. NR 15 TC 256 Z9 269 U1 16 U2 106 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD OCT PY 2013 VL 10 IS 10 BP 977 EP + DI 10.1038/NMETH.2598 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 226YP UT WOS:000325073800018 PM 23892898 ER PT J AU Barzel, B Barabisi, AL AF Barzel, Baruch Barabasi, Albert-Laszlo TI Universality in network dynamics SO NATURE PHYSICS LA English DT Article ID COMPLEX NETWORKS; REGULATORY NETWORKS; COMMUNITY STRUCTURE; GENE-EXPRESSION; SYNCHRONIZATION; DISTRIBUTIONS; MODELS; WORLD; LAW AB Despite significant advances in characterizing the structural properties of complex networks, a mathematical framework that uncovers the universal properties of the interplay between the topology and the dynamics of complex systems continues to elude us. Here we develop a self-consistent theory of dynamical perturbations in complex systems, allowing us to systematically separate the contribution of the network topology and dynamics. The formalism covers a broad range of steady-state dynamical processes and offers testable predictions regarding the system's response to perturbations and the development of correlations. It predicts several distinct universality classes whose characteristics can be derived directly from the continuum equation governing the system's dynamics and which are validated on several canonical network-based dynamical systems, from biochemical dynamics to epidemic spreading. Finally, we collect experimental data pertaining to social and biological systems, demonstrating that we can accurately uncover their universality class even in the absence of an appropriate continuum theory that governs the system's dynamics. C1 [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Barabisi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu FU DARPA [11645021]; DARPA Social Media in Strategic Communications project [W911NF-12-C-0028]; Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-02-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033]; National Institute of Health, Center of Excellence of Genomic Science (CEGS) [NIH CEGS 1P50HG4233]; National Institute of Health [1U01HL108630-01] FX We thank A. Vespignani, A. Sharma, F. Simini, J. Menche, S. Rabello, G. Ghoshal, Y-Y Liu, T. Jia, M. Posfai, C. Song, Y-Y. Ahn, N. Blumm, D. Wang, Z. Qu, M. Schich, D. Ghiassian, S. Gil, P. Hovel, J. Gao, M. Kitsak, M. Martino, R. Sinatra, G. Tsekenis, L. Chi, B. Gabriel, Q. Jin and Y. Li for discussions, and S. S. Aleva, S. Weiss, J. de Nicolo and A. Pawling for their support. This work was supported by DARPA Grant Number 11645021; The DARPA Social Media in Strategic Communications project under agreement number W911NF-12-C-0028; the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-02-0053; the Office of Naval Research under Agreement Number N000141010968 and the Defense Threat Reduction Agency awards WMD BRBAA07-J-2-0035 and BRBAA08-Per4-C-2-0033; the National Institute of Health, Center of Excellence of Genomic Science (CEGS), Grant number NIH CEGS 1P50HG4233; and the National Institute of Health, Award number 1U01HL108630-01. NR 53 TC 57 Z9 57 U1 5 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 J9 NAT PHYS JI Nat. Phys. PD OCT PY 2013 VL 9 IS 10 BP 673 EP 681 DI 10.1038/NPHYS2741 PG 9 WC Physics, Multidisciplinary SC Physics GA 228RL UT WOS:000325205000020 ER PT J AU Bellmunt, J Teh, BT Tortora, G Rosenberg, JE AF Bellmunt, Joaquim Teh, Bin T. Tortora, Giampaolo Rosenberg, Jonathan E. TI Molecular targets on the horizon for kidney and urothelial cancer SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID RENAL-CELL CARCINOMA; EAU INTERNATIONAL CONSULTATION; EPIDERMAL-GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; PHASE-II TRIAL; INVASIVE BLADDER-CANCER; HIPPEL-LINDAU DISEASE; CLEAR-CELL; ONCOLOGY-GROUP; SOLID TUMORS AB As whole-genome sequencing technology rapidly advances, the insights gained from deciphering cancer genomes are shifting the paradigm in the diagnosis and treatment of cancer with the promise of individualized treatment for each patient. Information gained in this way is extensive for certain cancers, but fairly limited in renal cell carcinomas and urothelial carcinoma. Mutations in multiple, potentially druggable genes have been identified in urothelial carcinomas; however, the association between molecular alterations and clinical outcome has not yet been robustly demonstrated. Data in this area are emerging in renal cell carcinoma, leading to the development of targeted agents that have improved overall survival. Unfortunately, these treatments rarely yield complete responses, are not curative, and development of resistance ensues. This Review will focus on the biology of non-hormonally driven urological cancers. We discuss how approaches using whole-genome sequencing can facilitate the discovery of biomarkers of drug sensitivity in both renal cell carcinomas and urothelial carcinomas. For renal cell carcinomas, we will describe how genomic and epigenomic mining has uncovered novel genes and pathways involved in tumorigenesis, tumour classification and mechanisms of resistance in the various subsets of this disease and the potential for exploiting these discoveries in the clinic. C1 [Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber & Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Bellmunt, Joaquim] Hosp del Mar IMIM IMAS, Barcelona 08003, Spain. [Teh, Bin T.] Natl Canc Ctr Singapore, Natl Canc Ctr, Singapore 169610, Singapore. [Tortora, Giampaolo] Univ Verona, Azienda Osped Univ Integrata, I-37134 Verona, Italy. [Rosenberg, Jonathan E.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RP Bellmunt, J (reprint author), Harvard Univ, Sch Med, Dana Farber & Brigham & Womens Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM joaquim_bellmunt@dfci.harvard.edu OI Tortora, Giampaolo/0000-0002-1378-4962; Rosenberg, Jonathan/0000-0003-2637-4249 NR 169 TC 16 Z9 17 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2013 VL 10 IS 10 BP 557 EP 570 DI 10.1038/nrclinonc.2013.155 PG 14 WC Oncology SC Oncology GA 226AQ UT WOS:000325007000005 PM 23982523 ER PT J AU Kaufman, HL Kirkwood, JM Hodi, FS Agarwala, S Amatruda, T Bines, SD Clark, JI Curti, B Ernstoff, MS Gajewski, T Gonzalez, R Hyde, LJ Lawson, D Lotze, M Lutzky, J Margolin, K McDermott, DF Morton, D Pavlick, A Richards, JM Sharfman, W Sondak, VK Sosman, J Steel, S Tarhini, A Thompson, JA Titze, J Urba, W White, R Atkins, MB AF Kaufman, Howard L. Kirkwood, John M. Hodi, F. Stephen Agarwala, Sanjiv Amatruda, Thomas Bines, Steven D. Clark, Joseph I. Curti, Brendan Ernstoff, Marc S. Gajewski, Thomas Gonzalez, Rene Hyde, Laura Jane Lawson, David Lotze, Michael Lutzky, Jose Margolin, Kim McDermott, David F. Morton, Donald Pavlick, Anna Richards, Jon M. Sharfman, William Sondak, Vernon K. Sosman, Jeffrey Steel, Susan Tarhini, Ahmad Thompson, John A. Titze, Jill Urba, Walter White, Richard Atkins, Michael B. TI The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID HIGH-RISK MELANOMA; DOSE RECOMBINANT INTERLEUKIN-2; COOPERATIVE-ONCOLOGY-GROUP; RENAL-CELL CARCINOMA; METASTATIC MALIGNANT-MELANOMA; INTERFERON-ALPHA THERAPY; STAGE-III MELANOMA; PHASE-I TRIAL; ADJUVANT THERAPY; RANDOMIZED-TRIAL AB Immunotherapy is associated with durable clinical benefit in patients with melanoma. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA. To achieve this goal, the Society for Immunotherapy of Cancer sponsored a panel of melanoma experts-including physicians, nurses, and patient advocates-to develop a consensus for the clinical application of tumour immunotherapy for patients with melanoma. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development. A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel. This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. From the peer-reviewed literature the consensus panel identified a role for interferon-alpha 2b, pegylated-interferon-alpha 2b, interleukin-2 (IL-2) and ipilimumab in the clinical management of melanoma. Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted. C1 [Kaufman, Howard L.; Bines, Steven D.; Titze, Jill] Rush Univ, Ctr Canc, Chicago, IL 60612 USA. [Kirkwood, John M.; Lotze, Michael; Tarhini, Ahmad] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA USA. [Agarwala, Sanjiv] St Lukes Canc Ctr, Houston, TX USA. [Clark, Joseph I.] Loyola Univ, Med Ctr, New Orleans, LA 70118 USA. [Curti, Brendan; Urba, Walter] Providence Canc Ctr, Providence, RI USA. [Ernstoff, Marc S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH USA. [Gajewski, Thomas] Univ Chicago, Chicago, IL 60637 USA. [Gonzalez, Rene] Univ Colorado, Boulder, CO 80309 USA. [Lawson, David] Emory Winship Canc Inst, Atlanta, GA USA. [Lutzky, Jose] Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. [Margolin, Kim; Thompson, John A.] Univ Washington, Seattle, WA 98195 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Morton, Donald] John Wayne Canc Inst, Santa Monica, CA USA. [Pavlick, Anna] NYU, New York, NY 10003 USA. [Richards, Jon M.] Lutheran Gen Hosp, Park Ridge, IL USA. [Sharfman, William] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Sondak, Vernon K.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Sosman, Jeffrey] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [White, Richard] Carolinas Med Ctr, Charlotte, NC USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Kaufman, HL (reprint author), Rush Univ, Ctr Canc, 1725 West Harrison St, Chicago, IL 60612 USA. EM howard_kaufman@rush.edu NR 80 TC 69 Z9 71 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2013 VL 10 IS 10 BP 588 EP 598 DI 10.1038/nrclinonc.2013.153 PG 11 WC Oncology SC Oncology GA 226AQ UT WOS:000325007000007 PM 23982524 ER PT J AU Fridlyand, J Simon, RM Walrath, JC Roach, N Buller, R Schenkein, DP Flaherty, KT Allen, JD Sigal, EV Scher, HI AF Fridlyand, Jane Simon, Richard M. Walrath, Jessica C. Roach, Nancy Buller, Richard Schenkein, David P. Flaherty, Keith T. Allen, Jeff D. Sigal, Ellen V. Scher, Howard I. TI Considerations for the successful co-development of targeted cancer therapies and companion diagnostics SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID CLINICAL-TRIAL DESIGNS; ADAPTIVE SIGNATURE DESIGN; GROWTH-FACTOR RECEPTOR; PREDICTIVE BIOMARKERS; MONOCLONAL-ANTIBODY; IMATINIB MESYLATE; WORKING GROUP; TUMOR-CELLS; ONCOLOGY; EXPRESSION AB As diagnostic tests become increasingly important for optimizing the use of drugs to treat cancers, the co-development of a targeted therapy and its companion diagnostic test is becoming more prevalent and necessary. In July 2011, the US Food and Drug Administration released a draft guidance that gave the agency's formal definition of companion diagnostics and introduced a drug-diagnostic co-development process for gaining regulatory approval. Here, we identify areas of drug-diagnostic co-development that were either not covered by the guidance or that would benefit from increased granularity, including how to determine when clinical studies should be limited to biomarker-positive patients, defining the diagnostically selected patient population in which to use a companion diagnostic, and defining and clinically validating a biomarker signature for assays that use more than one biomarker. We propose potential approaches that sponsors could use to deal with these challenges and provide strategies to help guide the future co-development of drugs and diagnostics. C1 [Fridlyand, Jane] Genentech Inc, San Francisco, CA 94080 USA. [Simon, Richard M.] US Natl Canc Inst, Bethesda, MD 20892 USA. [Walrath, Jessica C.; Allen, Jeff D.; Sigal, Ellen V.] Friends Canc Res, South Washington, DC 20036 USA. [Roach, Nancy] Fight Colorectal Canc, Alexandria, VA 22314 USA. [Buller, Richard] Pfizer, San Diego, CA 92121 USA. [Schenkein, David P.] Agios Pharmaceut, Cambridge, MA 02139 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RP Walrath, JC (reprint author), Friends Canc Res, 1800 M St NW,Suite 1050, South Washington, DC 20036 USA. EM jwalrath@focr.org NR 47 TC 24 Z9 25 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD OCT PY 2013 VL 12 IS 10 BP 743 EP 755 DI 10.1038/nrd4101 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 227XT UT WOS:000325149700013 PM 24008432 ER PT J AU Smith, MR AF Smith, Matthew R. TI CANCER ADT and acute kidney injury-causal or casual relationship? SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID ANDROGEN-DEPRIVATION THERAPY; PROSTATE-CANCER; RISK C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7030,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD OCT PY 2013 VL 9 IS 10 BP 568 EP 570 DI 10.1038/nrendo.2013.167 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224GJ UT WOS:000324870600002 PM 23959367 ER PT J AU Ryu, JH Walcott, BP Kahle, KT Sheth, SA Peterson, RT Nahed, BV Coumans, JVCE Simard, JM AF Ryu, Justine H. Walcott, Brian P. Kahle, Kristopher T. Sheth, Sameer A. Peterson, Randall T. Nahed, Brian V. Coumans, Jean-Valery C. E. Simard, J. Marc TI Induced and Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema Following Brain Injury SO NEUROCRITICAL CARE LA English DT Review DE Hypernatremia; Brain injuries; Brain edema; Intracranial pressure; Stroke; Renal insufficiency ID HYPERTONIC SALINE RESUSCITATION; RAISED INTRACRANIAL-PRESSURE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; BARRIER PERMEABILITY INCREASE; GOAL-DIRECTED THERAPY; NA+-K+-2CL(-) COTRANSPORT; HYPEROSMOLAR THERAPY; POTASSIUM CHANNEL; NEURONAL DAMAGE; ISCHEMIC-STROKE AB Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm. C1 [Ryu, Justine H.; Walcott, Brian P.; Kahle, Kristopher T.; Sheth, Sameer A.; Nahed, Brian V.; Coumans, Jean-Valery C. E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Ryu, Justine H.; Walcott, Brian P.; Kahle, Kristopher T.; Sheth, Sameer A.; Peterson, Randall T.; Nahed, Brian V.; Coumans, Jean-Valery C. E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ryu, Justine H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ryu, Justine H.; Walcott, Brian P.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Peterson, Randall T.] Broad Inst, Cambridge, MA USA. [Simard, J. Marc] Univ Maryland, Dept Neurosurg, Baltimore, MD 21201 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Department of Veterans Affairs (Baltimore); National Institute of Neurological Disorders and Stroke (NINDS) [NS060801, NS061808]; National Heart, Lung and Blood Institute [HL082517]; Department of the Army [W81XWH 1010898]; Christopher and Dana Reeve Foundation FX This work was supported by Grants to JMS from the Department of Veterans Affairs (Baltimore), the National Institute of Neurological Disorders and Stroke (NINDS) (NS060801; NS061808), the National Heart, Lung and Blood Institute (HL082517), the Department of the Army (W81XWH 1010898) and the Christopher and Dana Reeve Foundation. NR 100 TC 3 Z9 3 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD OCT PY 2013 VL 19 IS 2 BP 222 EP 231 DI 10.1007/s12028-013-9824-3 PG 10 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 221GB UT WOS:000324644800015 PM 23468135 ER PT J AU Diao, LH Hellier, JL Uskert-Newsom, J Williams, PA Staley, KJ Yee, AS AF Diao, Lihong Hellier, Jennifer L. Uskert-Newsom, Jessica Williams, Philip A. Staley, Kevin J. Yee, Audrey S. TI Diphenytoin, riluzole and lidocaine: Three sodium channel blockers, with different mechanisms of action, decrease hippocampal epileptiform activity SO NEUROPHARMACOLOGY LA English DT Article DE Epilepsy; Hyperexcitability; CA3; Diphenytoin; Riluzole; Lidocaine ID CA3 NETWORK ACTIVITY; AMYOTROPHIC-LATERAL-SCLEROSIS; RECURRENT COLLATERAL SYNAPSES; TEMPORAL-LOBE EPILEPSY; IN-VITRO; DENTATE GYRUS; RAT HIPPOCAMPUS; SPINAL-CORD; ANTICONVULSANT DRUGS; GLUTAMATE RELEASE AB Epilepsy is a condition affecting 1-2% of the population, characterized by the presence of spontaneous, recurrent seizures. The most common type of acquired epilepsy is temporal lobe epilepsy (TLE). Up to 30% of patients with TLE are refractory to currently available compounds, and there is an urgent need to identify novel targets for therapy. Here, we utilized the in-vitro CA3 burst preparation to examine alterations in network excitability, characterized by changes in interburst interval. Specifically, we show that bath application of three different sodium channel blockers-diphenytoin, riluzole, and lidocaine-slow spontaneous CA3 bursts. This in turn, decreased the epileptiform activity. These compounds work at different sites on voltage-gated sodium channels, but produce a similar network phenotype of decreased excitability. In the case of diphenytoin and riluzole, the change in network activity (i.e., increased interburst intervals) was persistent following drug washout. Lidocaine application, however, only increased the CA3 interburst interval when it was in the bath solution. Thus, its action was not permanent and resulted in returning CA3 bursting to baseline levels. These data demonstrate that the CA3 burst preparation provides a relatively easy and quick platform for identifying compounds that can decrease network excitability, providing the initial screen for further and more complex in-vivo, freely-behaving animal studies. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Diao, Lihong; Hellier, Jennifer L.; Uskert-Newsom, Jessica; Williams, Philip A.; Yee, Audrey S.] Univ Colorado Anschutz Med Campus, Aurora, CO 80045 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Yee, AS (reprint author), Univ Colorado Anschutz Med Campus, Pediat Neurol Sect, Mailstop 8105,POB 6511, Aurora, CO 80045 USA. EM audrey.yee@ucdenver.edu FU NINDS FX This work was funded by an NINDS K08 Award to Audrey S. Yee. We acknowledge past members of the Staley lab for helpful scientific discussion. NR 78 TC 7 Z9 8 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT PY 2013 VL 73 BP 48 EP 55 DI 10.1016/j.neuropharm.2013.04.057 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 229AD UT WOS:000325233300006 PM 23707481 ER PT J AU Sikalidis, AK Fitch, MD Fleming, SE AF Sikalidis, Angelos K. Fitch, Mark D. Fleming, Sharon E. TI Diet Induced Obesity Increases the Risk of Colonic Tumorigenesis in Mice SO PATHOLOGY & ONCOLOGY RESEARCH LA English DT Article DE Obesity; Colon cancer; C57BL/6J; Diet induced obesity; AOM ID ABERRANT CRYPT FOCI; BODY-MASS INDEX; MESSENGER-RNA EXPRESSION; COLORECTAL-CANCER RISK; METHYL-N-NITROSOUREA; HIGH-FAT DIET; PHYSICAL-ACTIVITY; WEIGHT-GAIN; RAT COLON; PROLIFERATION AB A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis. C1 [Sikalidis, Angelos K.; Fitch, Mark D.; Fleming, Sharon E.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Sikalidis, Angelos K.] Dana Farber Canc Inst, Harvard Inst Med, Boston, MA 02115 USA. RP Sikalidis, AK (reprint author), Dana Farber Canc Inst, Harvard Inst Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM angelos_sikalidis@dfci.harvard.edu FU NIH [NCI R03CA95974]; Agriculture Experiment Station at University of California, Berkeley FX This research was supported by NIH grant NCI R03CA95974, awarded to Dr. Sharon E. Fleming and the Agriculture Experiment Station at University of California, Berkeley. NR 43 TC 6 Z9 6 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1219-4956 J9 PATHOL ONCOL RES JI Pathol. Oncol. Res. PD OCT PY 2013 VL 19 IS 4 BP 657 EP 666 DI 10.1007/s12253-013-9626-0 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 221DU UT WOS:000324638600007 PM 23536280 ER PT J AU Sikalidis, AK Fitch, MD Fleming, SE AF Sikalidis, Angelos K. Fitch, Mark D. Fleming, Sharon E. TI Risk of Colonic Cancer is Not Higher in the Obese Lep(ob) Mouse Model Compared to Lean Littermates SO PATHOLOGY & ONCOLOGY RESEARCH LA English DT Article DE Leptin; Aberrant crypts; Tumors; Proliferation; Azoxymethane ID BODY-MASS INDEX; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; GROWTH-FACTOR; ZUCKER RATS; LEPTIN; INFLAMMATION; CELLS; METAANALYSIS; MICE AB Epidemiological data suggest that obesity increases the risk of colorectal cancer in humans. Given that diet-induced obesity mouse models verified the epidemiological data, the present study aimed to determine whether obese C57BL/6J-Lep(ob) male mice (a different obesity in vivo model) were at greater risk of colonic cancer than their lean male littermates. Risk of colonic tumorigenesis was assessed by numbers of aberrant crypts, aberrant crypt foci and colonic tumors. Proliferation of the colonic epithelia was assessed histochemically following administration of BrdU. Availability of the procarcinogen, azoxymethane (AOM) to target tissues was assessed by quantifying via HPLC plasma AOM concentrations during the 60 min period following AOM injection. When obese and lean mice were injected with azoxymethane (AOM) at doses calculated to provide equivalent AOM levels per kg lean body mass, obese animals had significantly fewer aberrant crypts/colon and fewer aberrant crypt foci/colon than the lean animals. Tumors were identified in the colonic mucosa of lean (4 tumors in 14 mice) but not obese (0 tumors in 15 mice) mice. Colonic cell proliferation was not significantly different for obese and lean mice. Because these results were unexpected, plasma AOM concentrations were measured and were found to be lower in the obese than lean mice. When plasma AOM levels were comparable for the lean and obese mice, the Lep(ob) mice continued to have significantly fewer aberrant crypt foci/colon than the lean mice, but differences were not statistically different for aberrant crypts/colon. Interestingly, obese Lep(ob) mice did not exhibit increased risk of colonic cancer as expected. Instead, Lep(ob) mice exhibited equivalent or lower risk of colon cancer when compared to the lean group. These results taken together with in vivo results from diet-induced obesity studies, imply that leptin may be responsible for the increased risk of colon cancer associated with obesity. C1 [Sikalidis, Angelos K.; Fitch, Mark D.; Fleming, Sharon E.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Sikalidis, Angelos K.] Dana Farber Canc Inst, Harvard Inst Med, Boston, MA 02115 USA. RP Sikalidis, AK (reprint author), Dana Farber Canc Inst, Harvard Inst Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM angelos_sikalidis@dfci.harvard.edu FU NIH [R01CA095972]; Agriculture Experiment Station at University of California, Berkeley FX Support was provided by NIH grant R01CA095972 awarded to Fleming SE and by the Agriculture Experiment Station at University of California, Berkeley. NR 52 TC 4 Z9 4 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1219-4956 J9 PATHOL ONCOL RES JI Pathol. Oncol. Res. PD OCT PY 2013 VL 19 IS 4 BP 867 EP 874 DI 10.1007/s12253-013-9656-7 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 221DU UT WOS:000324638600032 PM 23813464 ER PT J AU Flickinger, TE Rose, G Wilson, IB Wolfe, H Saha, S Korthuis, PT Massa, M Berry, S Laws, MB Sharp, V Moore, RD Beach, MC AF Flickinger, Tabor E. Rose, Gary Wilson, Ira B. Wolfe, Hannah Saha, Somnath Korthuis, Philip Todd Massa, Michele Berry, Stephen Laws, Michael Barton Sharp, Victoria Moore, Richard D. Beach, Mary Catherine TI Motivational interviewing by HIV care providers is associated with patient intentions to reduce unsafe sexual behavior SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Motivational interviewing; Physicians; HIV/AIDS; Sexual risk reduction; Counseling ID SAFER SEX; INFECTED PATIENTS; CLIENT LANGUAGE; SUBSTANCE USE; USE OUTCOMES; COMMUNICATION; INTERVENTION; PREVENTION; CLINICIAN; DRINKING AB Objective: Motivational interviewing (MI) can promote behavior change, but HIV care providers rarely have training in MI. Little is known about the use of MI-consistent behavior among untrained providers. This study examines the prevalence of such behaviors and their association with patient intentions to reduce high-risk sexual behavior. Methods: Audio-recorded visits between HIV-infected patients and their healthcare providers were searched for counseling dialog regarding sexual behavior. The association of providers' MI-consistence with patients' statements about behavior change was assessed. Results: Of 417 total encounters, 27 met inclusion criteria. The odds of patient commitment to change were higher when providers used more reflections (p = 0.017), used more MI consistent utterances (p = 0.044), demonstrated more empathy (p = 0.049), and spent more time discussing sexual behavior (p = 0.023). Patients gave more statements in favor of change (change talk) when providers used more reflections (p < 0.001) and more empathy (p < 0.001), even after adjusting for length of relevant dialog. Conclusion: Untrained HIV providers do not consistently use MI techniques when counseling patients about sexual risk reduction. However, when they do, their patients are more likely to express intentions to reduce sexual risk behavior. Practice implications: MI holds promise as one strategy to reduce transmission of HIV and other sexually transmitted infections. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Flickinger, Tabor E.; Massa, Michele; Berry, Stephen; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. [Rose, Gary] Massachusetts Sch Profess Psychol, Boston, MA USA. [Wilson, Ira B.; Laws, Michael Barton] Brown Univ, Dept Med, Providence, RI 02912 USA. [Wolfe, Hannah; Sharp, Victoria] Dept Med, New York, NY USA. [Saha, Somnath; Korthuis, Philip Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Saha, Somnath] Portland VA Med Ctr, Dept Med, Portland, OR USA. RP Flickinger, TE (reprint author), Johns Hopkins Univ, Sch Med, 2024 East Monument St,Suite 2-600, Baltimore, MD 21287 USA. EM tflicki1@jhmi.edu RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU Health Resources Service Administration; National Institutes of Health [5 T32 HL007180-35]; National Institute of Allergy and Infectious Disease [K23 A1084854]; National Institute of Drug Abuse [K23 DA019809]; Department of Veterans Affairs; Agency for Healthcare Research and Quality [K08 HS013903-05, AHRQ 290-01-0012]; NIMH [2K24MH092242]; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr. Flickinger was supported by the National Institutes of Health (5 T32 HL007180-35), Dr. Berry was supported by the National Institute of Allergy and Infectious Disease (K23 A1084854), Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019809), Dr. Saha was supported by the Department of Veterans Affairs, Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. Dr. Wilson was supported by a K24 from NIMH (2K24MH092242). None of the funders had a role in the design and conduct of this analysis, nor was it subject to their final approval. None of the authors have any relevant financial conflicts of interest. NR 51 TC 5 Z9 5 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2013 VL 93 IS 1 BP 122 EP 129 DI 10.1016/j.pec.2013.04.001 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 226TE UT WOS:000325058100017 PM 23647982 ER PT J AU Mautner, DB Pang, HC Brenner, JC Shea, JA Gross, KS Frasso, R Cannuscio, CC AF Mautner, Dawn B. Pang, Hauchie Brenner, Jeffrey C. Shea, Judy A. Gross, Kennen S. Frasso, Rosemary Cannuscio, Carolyn C. TI Generating Hypotheses About Care Needs of High Utilizers: Lessons from Patient Interviews SO POPULATION HEALTH MANAGEMENT LA English DT Article ID ADVERSE CHILDHOOD EXPERIENCES; EMERGENCY-DEPARTMENT; HOUSEHOLD DYSFUNCTION; FREQUENT USERS; HEALTH-CARE; CASE-MANAGEMENT; SERVICE USE; RISK; CONTINUITY; ADULTS AB Informed by a largely secondary and quantitative literature, efforts to improve care and outcomes for complex patients with high levels of emergency and hospital-based health care utilization have offered mixed results. This qualitative study identifies psychosocial factors and life experiences described by these patients that may be important to their care needs. Semi-structured interviews were conducted with 19 patients of the Camden Coalition of Healthcare Providers' Care Management Team. Investigators coded transcripts using a priori and inductively-derived codes, then identified 3 key themes: (1) Early-life instability and traumas, including parental loss, unstable or violent relationships, and transiency, informed many participants' health and health care experiences; (2) Many high utilizers described a history of difficult interactions with health care providers during adulthood; (3) Over half of the participants described the importance to their well-being of positive and caring relationships with primary health care providers and the outreach team. Additionally, the transient and vulnerable nature of this complex population posed challenges to follow-up, both for research and care delivery. These themes illuminate potentially important hypotheses to be explored in more generalizable samples using robust and longitudinal methods. Future work should explore the prevalence and impact of adverse childhood experiences among high utilizers, and the different types of relationships they have with providers. Investigators should test new modes of care delivery that attend to patients' trauma histories. This qualitative study was well suited to provide insight into the life stories of these complex, vulnerable patients, informing research questions for further investigation. (Population Health Management 2013;16:S-26-S-33) C1 [Mautner, Dawn B.] Thomas Jefferson Univ, Dept Family & Community Med, Philadelphia, PA 19107 USA. [Mautner, Dawn B.] Thomas Jefferson Univ, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19107 USA. [Pang, Hauchie; Frasso, Rosemary] Univ Penn, Sch Social Policy & Practice, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Brenner, Jeffrey C.; Gross, Kennen S.] Camden Coalit Healthcare Providers, Camden, NJ USA. [Brenner, Jeffrey C.; Gross, Kennen S.] Rowan Univ, Cooper Med Sch, Dept Family Med, Camden, NJ USA. [Shea, Judy A.; Cannuscio, Carolyn C.] Philadelphia VA, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Shea, Judy A.] Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.] Univ Penn, Perelman Sch Med, Mixed Methods Res Lab, Philadelphia, PA 19104 USA. RP Mautner, DB (reprint author), Thomas Jefferson Univ, Dept Family & Community Med, 1015 Walnut St,401 Curtis, Philadelphia, PA 19107 USA. EM dawn.mautner@jefferson.edu FU Robert Wood Johnson Health and Society Scholars Program Fund at the University of Pennsylvania FX The authors appreciate the sponsorship of the Robert Wood Johnson Health and Society Scholars Program Fund at the University of Pennsylvania. We wish to acknowledge the support of Katrina Armstrong, MD, MSCE and Glenda Wrenn, MD, MA throughout the process of developing this project. Finally, we wish to thank the Robert Wood Johnson Foundation Clinical Scholars Program at the University of Pennsylvania for the postdoctoral training support of Dr. Mautner, during which this work was completed. Parts of this work have been presented at the Robert Wood Johnson Clinical Scholars' National Meeting in November 2011. NR 45 TC 11 Z9 11 U1 7 U2 26 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1942-7891 EI 1942-7905 J9 POPUL HEALTH MANAG JI Popul. Health Manag. PD OCT 1 PY 2013 VL 16 SU 1 BP S26 EP S33 DI 10.1089/pop.2013.0033 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 224MT UT WOS:000324891700007 PM 24070247 ER PT J AU Peloquin, G Chen, YB Fathi, AT AF Peloquin, Grace L. Chen, Yi-Bin Fathi, Amir T. TI The evolving landscape in the therapy of acute myeloid leukemia SO PROTEIN & CELL LA English DT Review DE acute myeloid leukemia; hypomethylating; FLT3; gemtuzumab ozogamicin ID ACUTE MYELOGENOUS LEUKEMIA; INTERNAL TANDEM DUPLICATION; SOUTHWEST-ONCOLOGY-GROUP; REFRACTORY HEMATOLOGIC MALIGNANCIES; CONSTITUTIVELY ACTIVATED FLT3; ACUTE NONLYMPHOCYTIC LEUKEMIA; TRIAL COMPARING IDARUBICIN; TOPOISOMERASE-II INHIBITOR; UNTREATED ADULT PATIENTS; HIGH-DOSE CYTARABINE AB Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of myeloid precursors arrested in their maturation, creating a diverse disease entity with a wide range of responses to historically standard treatment approaches. While significant progress has been made in characterizing and individualizing the disease at diagnosis to optimally inform those affected, progress in treatment to reduce relapse and induce remission has been limited thus far. In addition to a brief summary of the factors that shape prognostication at diagnosis, this review attempts to expand on the current therapies under investigation that have shown promise in treating AML, including hypomethylating agents, gemtuzumab ozogamicin, FLT3 tyrosine kinase inhibitors, antisense oligonucleotides, and other novel therapies, including aurora kinases, mTOR and PI3 kinase inhibitors, PIM kinase inhibitors, HDAC inhibitors, and IDH targeted therapies. With these, and undoubtedly many others in the future, it is the hope that by combining more accurate prognostication with more effective therapies, patients will begin to have a different, and more complete, outlook on their disease that allows for safer and more successful treatment strategies. C1 [Peloquin, Grace L.; Chen, Yi-Bin; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Fathi, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. EM afathi@partners.org FU Otsuka; Seattle Genetics FX Grace Peloquin declares that she has no conflict of interest. Amir Fathi has served on advisory boards with Teva, Agios, and Seattle Genetics, and part of his clinical trial research is funded by Millennium and Seattle Genetics. A portion of the clinical trial research performed by Yi-Bin Chen is funded by Otsuka and Seattle Genetics. NR 111 TC 8 Z9 9 U1 1 U2 19 PU HIGHER EDUCATION PRESS PI BEIJING PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA SN 1674-800X J9 PROTEIN CELL JI Protein Cell PD OCT PY 2013 VL 4 IS 10 BP 735 EP 746 DI 10.1007/s13238-013-3057-2 PG 12 WC Cell Biology SC Cell Biology GA 231QJ UT WOS:000325432000004 PM 23982740 ER PT J AU Taylor, SW O'Cleirigh, C Mayer, KH Safren, SA AF Taylor, S. Wade O'Cleirigh, Conall Mayer, Kenneth H. Safren, Steven A. TI HIV-infected men who have sex with men who engage in very high levels of transmission risk behaviors: Establishing a context for novel prevention interventions SO PSYCHOLOGY HEALTH & MEDICINE LA English DT Article DE HIV infection; MSM; gay and bisexual men; HIV prevention; risky sexual behavior ID POSITIVE MEN; QUALITATIVE DESCRIPTION; PERSONS AWARE; MORAL AGENCY; GAY MEN; HEALTH; ASSUMPTIONS; INTIMACY; UNAWARE; MSM AB Men who have sex with men (MSM) comprise the largest risk group of individuals living with HIV in the USA and have the highest rates of new infections. A minority of HIV-infected MSM engage in unprotected anal intercourse after learning about their infection, potentially transmitting the virus to others. The current study sought to generate self-generated descriptive themes, from a group of HIV-infected MSM who reported high rates of sexual transmission risk behavior that may be relevant for understanding sexual risk in this group. Five descriptive themes emerged during content analysis: (a) serostatus attribution, (b) assumption of sexual partner's responsibility for safer sex, (c) sexual sensation seeking, (d) ongoing substance use, and (e) dissatisfaction with current relationships. Traditional HIV transmission risk reduction interventions that have been known to have only modest effects should be augmented by developing HIV prevention strategies for this subgroup of MSM to address these salient themes. C1 [Taylor, S. Wade; O'Cleirigh, Conall; Mayer, Kenneth H.; Safren, Steven A.] Fenway Inst, Fenway Hlth, Boston, MA USA. [O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Cleirigh, Conall; Mayer, Kenneth H.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Taylor, SW (reprint author), Fenway Inst, Fenway Hlth, Boston, MA USA. EM wtaylor@fenwayhealth.org FU Harvard University Center for AIDS Research: (National Institute of Health /NIAID) [P30-AI 060354] FX This study was supported by a series of feasibility grant awards by Harvard University Center for AIDS Research: (P30-AI 060354 - National Institute of Health /NIAID) Characteristics of HIV-infected MSM who Report Very High Rates of Sexual Transmission Risk (PI: of CFAR Walker, B; PI of development award O'Cleirigh, C) and HIV Prevention Intervention Development in Very High Risk MSM (PI: O'Cleirigh, C). NR 47 TC 1 Z9 1 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-8506 J9 PSYCHOL HEALTH MED JI Psychol. Health Med. PD OCT 1 PY 2013 VL 18 IS 5 BP 576 EP 587 DI 10.1080/13548506.2012.756537 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 223ZU UT WOS:000324851800008 ER PT J AU Chung, RJ Sherman, L Goodman, E Bickham, DS Rich, M AF Chung, Richard J. Sherman, Laura Goodman, Elizabeth Bickham, David S. Rich, Michael TI Exploring the Perspectives of Obese Adolescent Girls SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE adolescents; youth; behavior change; body image; health behavior; motivation; obesity; overweight; visual methods ID ILLNESS EXPERIENCE; PREVENTION; OVERWEIGHT; BEHAVIORS; CHILDREN; WEIGHT; VIDEO AB To understand obese adolescent girls' perspectives regarding their weight and health we studied video intervention/prevention assessment audiovisual narratives created by 14 obese girls ages 12 to 20 years. The narratives included interviews, monologues, and daily activities. Themes included illness conceptualizations, health concerns, health misinformation, and distress regarding appearance deriving from both within and without. The predominant theme was ambivalence about obesity. Close examination of these themes revealed potential footholds for intervention. Sensitive exploration of issues such as appearance and psychosocial distress might strengthen the patient-clinician partnership in identifying a patient's strengths and motivating weight loss. C1 [Chung, Richard J.] Duke Univ, Sch Med, Durham, NC 27704 USA. [Sherman, Laura; Bickham, David S.; Rich, Michael] Childrens Hosp, Ctr Media & Child Hlth, Boston, MA 02115 USA. [Goodman, Elizabeth] MassGen Hosp Children, Boston, MA USA. RP Chung, RJ (reprint author), Duke Univ, Sch Med, 4020 North Roxboro St, Durham, NC 27704 USA. EM richard.chung@duke.edu OI Goodman, Elizabeth/0000-0002-9640-9884 NR 17 TC 3 Z9 3 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD OCT PY 2013 VL 23 IS 10 SI SI BP 1369 EP 1376 DI 10.1177/1049732313505777 PG 8 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 227ZB UT WOS:000325153100007 PM 24043347 ER PT J AU Derrington, TM Kotelchuck, M Plummer, K Cabral, H Lin, AE Belanoff, C Shin, M Correa, A Grosse, SD AF Derrington, Taletha Mae Kotelchuck, Milton Plummer, Katrina Cabral, Howard Lin, Angela E. Belanoff, Candice Shin, Mikyong Correa, Adolfo Grosse, Scott D. TI Racial/ethnic differences in hospital use and cost among a statewide population of children with Down syndrome SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Down syndrome; Congenital heart defects; Hospital use; Hospital cost; Racial/ethnic disparities ID PRIVATELY INSURED POPULATION; METROPOLITAN ATLANTA; CONGENITAL-DEFECTS; ETHNIC DISPARITIES; ASTHMA MANAGEMENT; YOUNG-CHILDREN; UNITED-STATES; MEDICAL HOME; CARE; INFANTS AB Children with Down syndrome (DS) use hospital services more often than children without DS, but data on racial/ethnic variations are limited. This study generated population-based estimates of hospital use and cost to 3 years of age by race/ethnicity among children with DS in Massachusetts using birth certificates linked to birth defects registry and hospital discharge data from 1999 to 2004. Hospital use (>= 1 post-birth hospitalization and median days hospitalized birth and post-birth) and reasons for hospitalization were compared across maternal race/ethnicity using relative risk (RR) and Wilcoxon rank sums tests, as appropriate. Costs were calculated in 2011 United States dollars. Greater hospital use was observed among children with DS with Hispanic vs. Non-Hispanic White (NHW) mothers (post-birth hospitalization: RR 1.4; median days hospitalized: 20.0 vs. 11.0, respectively). Children with DS and congenital heart defects of Non-Hispanic Black (NHB) mothers had significantly greater median days hospitalized than their NHW counterparts (24.0 vs. 16.0, respectively). Respiratory diagnoses were listed more often among children with Hispanic vs. NHW mothers (50.0% vs. 29.1%, respectively), and NHBs had more cardiac diagnoses (34.1% vs. 21.5%, respectively). The mean total hospital cost was nine times higher among children with DS ($40,075) than among children without DS ($4053), and total costs attributable to DS were almost $18 million. Median costs were $22,781 for Hispanics, $18,495 for NHBs, and $13,947 for NHWs. Public health interventions should address the higher rates of hospital use and hospitalizations for respiratory and cardiac diseases among racial/ethnic minority children with DS in Massachusetts. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Derrington, Taletha Mae; Kotelchuck, Milton; Plummer, Katrina; Belanoff, Candice] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. [Derrington, Taletha Mae] SRI Int, Educ Div, Ctr Educ & Human Serv, Menlo Pk, CA 94025 USA. [Kotelchuck, Milton] MassGen Hosp Children, Ctr Child &Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Cabral, Howard] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Lin, Angela E.] Massachusetts Ctr Birth Defects Res & Prevent, Massachusetts Dept Publ Hlth, Boston, MA 02108 USA. [Lin, Angela E.] MassGen Hosp Children, Med Genet Unit, Boston, MA 02114 USA. [Shin, Mikyong; Correa, Adolfo] Ctr Dis Control & Prevent, Div Birth Defects & Dev Disabil, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Shin, Mikyong] Ctr Dis Control & Prevent, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Jackson, MS 39213 USA. [Grosse, Scott D.] Ctr Dis Control & Prevent, Div Blood Disorders, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. RP Derrington, TM (reprint author), 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM taletha.derrington@sri.com; mkotelchuck@partners.org; katrinaplummer@gmail.com; hjcab@bu.edu; alin@partners.org; cbelanoff@bu.edu; fqx6@cdc.org; acorrea@umc.edu; sgrosse@cdc.gov FU Intramural CDC HHS [CC999999]; PHS HHS [200-2009-31671, 200-2007-22997] NR 39 TC 5 Z9 5 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-4222 J9 RES DEV DISABIL JI Res. Dev. Disabil. PD OCT PY 2013 VL 34 IS 10 BP 3276 EP 3287 DI 10.1016/j.ridd.2013.06.022 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 225NB UT WOS:000324968500026 PM 23892874 ER PT J AU Meschia, JF Arnett, DK Ay, H Brown, RD Benavente, OR Cole, JW de Bakker, PIW Dichgans, M Doheny, KF Fornage, M Grewal, RP Gwinn, K Jern, C Conde, JJ Johnson, JA Jood, K Laurie, CC Lee, JM Lindgren, A Markus, HS McArdle, PF McClure, LA Mitchell, BD Schmidt, R Rexrode, KM Rich, SS Rosand, J Rothwell, PM Rundek, T Sacco, RL Sharma, P Shuldiner, AR Slowik, A Wassertheil-Smoller, S Sudlow, C Thijs, VNS Woo, D Worrall, BB Wu, O Kittner, SJ AF Meschia, James F. Arnett, Donna K. Ay, Hakan Brown, Robert D. Benavente, Oscar R. Cole, John W. de Bakker, Paul I. W. Dichgans, Martin Doheny, Kimberly F. Fornage, Myriam Grewal, Raji P. Gwinn, Katrina Jern, Christina Conde, Jordi Jimenez Johnson, Julie A. Jood, Katarina Laurie, Cathy C. Lee, Jin-Moo Lindgren, Arne Markus, Hugh S. McArdle, Patrick F. McClure, Leslie A. Mitchell, Braxton D. Schmidt, Reinhold Rexrode, Kathryn M. Rich, Stephen S. Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Sacco, Ralph L. Sharma, Pankaj Shuldiner, Alan R. Slowik, Agnieszka Wassertheil-Smoller, Sylvia Sudlow, Cathie Thijs, Vincent N. S. Woo, Daniel Worrall, Bradford B. Wu, Ona Kittner, Steven J. CA NINDS SiGN Study TI Stroke Genetics Network (SiGN) Study Design and Rationale for a Genome-Wide Association Study of Ischemic Stroke Subtypes SO STROKE LA English DT Article DE cerebral infarct; genetics; genomics ID CAUSATIVE CLASSIFICATION; ATHEROSCLEROTIC STROKE; RISK; VARIANTS; SYSTEM; HEALTH AB Background and Purpose Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research-generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. Conclusions The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke. C1 [Meschia, James F.] Mayo Clin Jacksonville, Jacksonville, FL USA. [Arnett, Donna K.; McClure, Leslie A.] Univ Alabama Birmingham, Birmingham, AL USA. [Brown, Robert D.] Mayo Clin Rochester, Rochester, MN USA. [Ay, Hakan; Rosand, Jonathan; Wu, Ona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Benavente, Oscar R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Cole, John W.; McArdle, Patrick F.; Mitchell, Braxton D.; Shuldiner, Alan R.; Kittner, Steven J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Cole, John W.; McArdle, Patrick F.; Mitchell, Braxton D.; Shuldiner, Alan R.; Kittner, Steven J.] Vet Adm Med Ctr, Baltimore, MD 21218 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [de Bakker, Paul I. W.] MIT, Broad Inst Harvard, Cambridge, MA USA. [Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Munich, Germany. [Doheny, Kimberly F.] Johns Hopkins Univ, Baltimore, MD USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Grewal, Raji P.] St Francis Med Ctr, Lynwood, CA USA. [Gwinn, Katrina] NINDS Neurogenet Cluster, Bethesda, MD USA. [Conde, Jordi Jimenez] Univ Mar, IMIM Hosp, Barcelona, Spain. [Johnson, Julie A.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Jern, Christina; Jood, Katarina] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Laurie, Cathy C.] Univ Washington, Seattle, WA 98195 USA. [Lee, Jin-Moo] Washington Univ, Sch Med, St Louis, MO USA. [Lindgren, Arne] Lund Univ, Lund, Sweden. [Markus, Hugh S.] St Georges Univ London, London, England. [Schmidt, Reinhold] Med Univ Graz, Graz, Austria. [Rexrode, Kathryn M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rich, Stephen S.; Worrall, Bradford B.] Univ Virginia, Charlottesville, VA USA. [Rothwell, Peter M.] Radcliffe Infirm, Oxford OX2 6HE, England. [Rundek, Tatjana; Sacco, Ralph L.] Univ Miami, Coral Gables, FL 33124 USA. [Sharma, Pankaj] Imperial Coll London, London, England. [Slowik, Agnieszka] Jagiellonian Univ, Krakow, Poland. [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Sudlow, Cathie] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Thijs, Vincent N. S.] Univ Ziekenhuizen Leuven, Louvain, Belgium. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA. RP Kittner, SJ (reprint author), Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. EM skittner@umaryland.edu RI de Bakker, Paul/B-8730-2009; Lee, Jin-Moo/K-2024-2015; McClure, Leslie/P-2929-2015; JIMENEZ-CONDE, JORDI/C-1941-2012; OI de Bakker, Paul/0000-0001-7735-7858; Lee, Jin-Moo/0000-0002-3979-0906; Thijs, Vincent/0000-0002-6614-8417; Rexrode, Kathryn/0000-0003-3387-8429; Bevan, Steve/0000-0003-0490-6830; Mitchell, Braxton/0000-0003-4920-4744; Anderson, Christopher/0000-0002-0053-2002; Gwinn, Katrina/0000-0002-8277-651X FU National Institute of Neurological Disorders and Stroke (NINDS) [U01 NS069208]; Ministerio de Sanidad y Consumo de Espana; Instituto de Salud Carlos III (ISC III) [PI051737]; GWA study of LeukoAraiosis (GWALA) Bases geneticas de la leucoaraiosis; Fondos de Investigacion Sanitaria ISC III [PI10/02064]; Fondos FEDER/EDRF Red de Investigacion Cardiovascular [RD12/0042/0020]; Fundacio la Marato TV3 [76/C/2011]; British Council (UKIERI); Henry Smith Charity; Department of Health (UK); Department of Health; National Institutes of Health [HHSN268200782096C, NS 030678]; Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh; Binks Trust; Council Brain Imaging Research Centre; Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility; Scottish Imaging Network - A Platform for Scientific Excellence (SINAPSE) collaboration; Scottish Funding Council; Chief Scientist Office; Wellcome Trust as part of the Wellcome Trust Case Control Consortium [085475/B/08/Z, 085475/Z/08/Z, WT084724MA]; National Institutes of Health Genes Affecting Stroke Risks and Outcomes Study (GASROS) [K23 NS042720]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; NINDS [K23NS042695, R01NS059727, R01 NS42733, R01 NS39987, R37 NS029993, R01 NS27517]; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Keane Stroke Genetics Fund; National Center for Research Resources [U54RR020278]; National Institutes of Health Genes, Environment and Health Initiative (GEI)as part of the Gene Environment Association Studies (GENEVA) consortium under GEI [U01 HG004436]; Mid-Atlantic Nutrition and Obesity Research Center [P30 DK072488]; Office of Research and Development, Medical Research Service; Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; National Institutes of Health (NIH) Office of Research on Women's Health [R01 NS45012, U01 NS069208-01]; Austrian Science Fund (FWF) [P20545-P05, P13180, I904-B13]; National Institute on Aging [Z01 AG000954-06, Z01 AG000015-50]; Polish Ministry of Science and Higher Education for Leading National Research Centers (KNOW); Medical College, Jagiellonian University in Krakow, Poland [K/ZDS/002848]; Department of Neurology of the University Hospitals Leuven; Fundamental Clinical Research grant from FWO Flanders [1.8.009.08.N.00, 1800913N]; Swedish Research Council, Region Skane [K2010-61X-20378-04-3]; Freemasons Lodge of Instruction EOS in Lund; King Gustaf V's and Queen Victoria's Foundation; Lund University; Swedish Stroke Association; New Jersey Neuroscience Institute/JFK Medical Center, Edison, NJ; Neurogenetics Foundation, Cranbury, NJ; Department of Neurology at University of Miami Miller School of Medicine; Evelyn McKnight Brain Institute; National Institutes of Health from the National Heart Lung and Blood Institute [HL088521, HL34594]; National Cancer Institute [CA87969, CA49449]; Stroke Association; Medical Research Council; Wellcome Trust; Dunhill Medical Trust; National Institutes of Health Research (NIHR); NIHR Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust; University of Oxford; NIHR; NINDS, National Institutes of Health, and Department of Health and Human Service [U01 NS041588]; Swedish Research Council [K2011-65X-14605-09-6]; Swedish Heart and Lung Foundation [20100256]; Swedish state/Sahlgrenska University Hospital [ALFGBG-148861]; Swedish Society of Medicine; Rune and Ulla Amlov Foundation; US National Institute of Health and Neurological Disorders and Stroke [U01NS38529-04A1]; Wellcome Trust, as part of the Wellcome Trust Case Control Consortium [085475/B/08/Z, 085475/Z/08/Z, WT084724MA]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118, 32119, 32122, 42107-26, 42129-32, 44221]; National Institutes of Neurological Disorders and Stroke [R01NS042618]; Washington University SPOTRIAS Center [P50 NS055977]; Barnes-Jewish Hospital Foundation; [R01 NS073346] FX SiGN: The study was funded by a cooperative agreement grant from the National Institute of Neurological Disorders and Stroke (NINDS) U01 NS069208.; BASICMAR: The BASICMAR Genetic Study was supported by the Ministerio de Sanidad y Consumo de Espana, Instituto de Salud Carlos III (ISC III) with the grants: "Registro BASICMAR" Funding for Research in Health (PI051737); GWA study of LeukoAraiosis (GWALA) Bases geneticas de la leucoaraiosis. Estudio de Genome Wide Association en poblacion espanola. Consorcio Espanol de Genetica del Ictus (Genestroke). "GWALA project" from Fondos de Investigacion Sanitaria ISC III (PI10/02064); and Fondos FEDER/EDRF Red de Investigacion Cardiovascular (RD12/0042/0020). Additional support provided by the Fundacio la Marato TV3 with the grant "Genetic contribution to functional Outcome and Disability after Stroke (GOD's) project" (76/C/2011). Assistance with data cleaning was provided by the Research in Cardiovascular and Inflammatory Diseases Program of Institute of Medical Investigations Mar, Hospital del Mar, and the Barcelona Biomedical Research Park.; BRAINS: BRAINS was supported by the British Council (UKIERI), Henry Smith Charity, and Department of Health (UK). Dr Sharma was supported by a Department of Health Senior Fellowship. CIDR: Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University (contract number HHSN268200782096C).; EDINBURGH: The Edinburgh Stroke Study was supported by the Wellcome Trust (clinician scientist award to Dr Sudlow) and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre (www.sbirc.ed.ac.uk), Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility and part of the Scottish Imaging Network - A Platform for Scientific Excellence (SINAPSE) collaboration (www.sinapse.ac.uk), funded by the Scottish Funding Council and the Chief Scientist Office. Genotyping was performed at the Wellcome Trust Sanger Institute in the UK and funded by the Wellcome Trust as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA).; GASROS: The Massachusetts General Hospital Stroke Genetics Group was supported by the National Institutes of Health Genes Affecting Stroke Risks and Outcomes Study (GASROS) grant K23 NS042720, the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research 0775010N, and NINDS K23NS042695, R01NS059727, the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, and by the Keane Stroke Genetics Fund. Genotyping services were provided by the Broad Institute Center for Genotyping and Analysis, supported by grant U54RR020278 from the National Center for Research Resources.; GCNKSS: The Greater Cincinnati/Northern Kentucky Stroke Study was supported by the National Institutes of Health (NS 030678).; GEOS: The GEOS Study was supported by the National Institutes of Health Genes, Environment and Health Initiative (GEI) grant U01 HG004436, as part of the Gene Environment Association Studies (GENEVA) consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488) and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University CIDR, which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University (contract number HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S Weir). Study recruitment and assembly of data sets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and by grants from the NINDS and the National Institutes of Health (NIH) Office of Research on Women's Health (R01 NS45012, U01 NS069208-01).; GRAZ: The Austrian Stroke Prevention Study was supported by the Austrian Science Fund (FWF) grant numbers P20545-P05 and P13180 and I904-B13 (Era-Net). The Medical University of Graz supports the databases of the Graz Stroke Study and the Austrian Stroke Prevention Study.; ISGS and SWISS: The Ischemic Stroke Genetics Study (ISGS) was supported by the NINDS (R01 NS42733; PI Dr Meschia). The Sibling with Ischemic Stroke Study (SWISS) was supported by the NINDS (R01 NS39987; PI Dr Meschia). Both SWISS and ISGS received additional support, in part, from the Intramural Research Program of the National Institute on Aging (Z01 AG000954-06; PI Andrew Singleton). SWISS and ISGS used samples and clinical data from the NIH-NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), human subjects protocol numbers 2003-081 and 2004-147. SWISS and ISGS used stroke-free participants from the Baltimore Longitudinal Study of Aging (BLSA) as controls with the permission of Dr Luigi Ferrucci. The inclusion of BLSA samples was supported, in part, by the Intramural Research Program of the National Institute on Aging (Z01 AG000015-50), human subjects protocol number 2003-078. This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (http://biowulf.nih.gov).; KRAKOW: Phenotypic data and genetic specimens collection were funded by the grant from the Polish Ministry of Science and Higher Education for Leading National Research Centers (KNOW) and by the grant from the Medical College, Jagiellonian University in Krakow, Poland: K/ZDS/002848.; LEUVEN: The Leuven Stroke genetics study was supported by personal research funds from the Department of Neurology of the University Hospitals Leuven. Vincent Thijs is supported by a Fundamental Clinical Research grant from FWO Flanders (numbers 1.8.009.08.N.00 and 1800913N).; LUND: The Lund Stroke Register was supported by the Swedish Research Council (K2010-61X-20378-04-3), Region Skane, the Freemasons Lodge of Instruction EOS in Lund, King Gustaf V's and Queen Victoria's Foundation, Lund University, and the Swedish Stroke Association. Biobank services were provided by Region Skane Competence Centre (RSKC Malmo), Skane University Hospital, Malmo, Sweden, and Biobank, LabmedicinSkane, University and Regional Laboratories Region Skane, Sweden.; MCISS: The Middlesex County Ischemic Stroke Study (MCISS) was supported by intramural funding from the New Jersey Neuroscience Institute/JFK Medical Center, Edison, NJ, and The Neurogenetics Foundation, Cranbury, NJ. We acknowledge Dr Souvik Sen for his advice and encouragement in the initiation and design of this study.; MIAMISR and NOMAS(S): The Northern Manhattan Study (NOMAS) was supported by grants from the NINDS (R37 NS029993, R01 NS27517). The Cerebrovascular Biorepository at University of Miami/Jackson Memorial Hospital (The Miami Stroke Registry, Institutional Review Board No. 20070386) was supported by the Department of Neurology at University of Miami Miller School of Medicine and Evelyn McKnight Brain Institute. Biorepository and DNA extraction services were provided by the Hussmann Institute for Human Genomics at the Miller School of Medicine.; MUNICH: The MUNICH study was supported by the Vascular Dementia Research Foundation and the Jackstaedt Stiftung.; NHS: The Nurses' Health Study work on stroke is supported by grants from the National Institutes of Health, including HL088521 and HL34594 from the National Heart Lung and Blood Institute, as well as grants from the National Cancer Institute funding the questionnaire follow-up and blood collection: CA87969 and CA49449.; OXVASC: The Oxford Vascular Study was supported by the Stroke Association, Medical Research Council, Wellcome Trust, Dunhill Medical Trust, National Institutes of Health Research (NIHR), and NIHR Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford. Rothwell is in receipt of Senior Investigator Awards from the Wellcome Trust and the NIHR.; REGARDS: The Reasons for Geographic and Racial Differences in Stroke Study was supported by a cooperative agreement U01 NS041588 from the NINDS, National Institutes of Health, and Department of Health and Human Service. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org.; SAHLSIS: SAHLSIS was supported by the Swedish Research Council (K2011-65X-14605-09-6), the Swedish Heart and Lung Foundation (20100256), the Swedish state/Sahlgrenska University Hospital (ALFGBG-148861), the Swedish Stroke Association, the Swedish Society of Medicine, and the Rune and Ulla Amlov Foundation.; SPS3: The Secondary Prevention of Small Subcortical Strokes trial was funded by the US National Institute of Health and Neurological Disorders and Stroke grant No. U01NS38529-04A1 (principal investigator, O.R.B.; co-principal investigator, R. G. H.). The SPS3 Genetic Substudy (SPS3-GENES) was funded by R01 NS073346 (co-principal investigators, J.A.J, O.R.B, A. R. S.).; ST. GEORGE'S: The principal funding for this study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). Collection of some of the St George's stroke cohort was supported by project grant support from the Stroke Association.; WHI: The Women's Health Initiatives (WHI) program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118 to 32119, 32122, 42107-26, 42129-32, and 44221. The Hormones and Biomarkers Predicting Stroke (HaBPS) was supported by a grant from the National Institutes of Neurological Disorders and Stroke (R01NS042618).; WUSTL: The collection, extraction of DNA from blood, and storage of specimens were supported by the Washington University SPOTRIAS Center grant (P50 NS055977, NINDS, NIH). Basic demographic and clinical characterization of stroke phenotype was prospectively collected in the Cognitive Rehabilitation and Recovery Group (CRRG) registry. The Recovery Genomics after Ischemic Stroke (ReGenesIS) study was supported by a grant from the Barnes-Jewish Hospital Foundation. NR 15 TC 19 Z9 19 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2013 VL 44 IS 10 BP 2694 EP 2702 DI 10.1161/STROKEAHA.113.001857 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 223TC UT WOS:000324831900020 PM 24021684 ER PT J AU Merwick, A Albers, GW Arsava, EM Ay, H Calvet, D Coutts, SB Cucchiara, BL Demchuk, AM Giles, MF Mas, JL Olivot, JM Purroy, F Rothwell, PM Saver, JL Sharma, VK Tsivgoulis, G Kelly, PJ AF Merwick, Aine Albers, Gregory W. Arsava, Ethem M. Ay, Hakan Calvet, David Coutts, Shelagh B. Cucchiara, Brett L. Demchuk, Andrew M. Giles, Matthew F. Mas, Jean-Louis Olivot, Jean Marc Purroy, Francisco Rothwell, Peter M. Saver, Jeffrey L. Sharma, Vijay K. Tsivgoulis, Georgios Kelly, Peter J. TI Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment SO STROKE LA English DT Article DE carotid stenosis; ischemic attack; transient; statin ID ACUTE CORONARY SYNDROMES; HIGH-DOSE ATORVASTATIN; RECURRENT STROKE; TRIAL; TIA; ENDARTERECTOMY; PREVENTION AB Background and Purpose Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. Methods We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. Results In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). Conclusions In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required. C1 [Kelly, Peter J.] Mater Univ Hosp, Neurovasc Unit Translat & Therapeut Res, Dublin 7, Ireland. [Merwick, Aine; Kelly, Peter J.] Mater Misericordiae Univ Hosp, Dublin Acad Med Ctr, Neurovasc Unit Translat & Therapeut Res, Stroke Serv, Dublin, Ireland. [Merwick, Aine; Kelly, Peter J.] Mater Misericordiae Univ Hosp, Dublin Acad Med Ctr, Dept Neurol, Dublin, Ireland. [Albers, Gregory W.; Olivot, Jean Marc] Stanford Stroke Ctr, Dept Neurol & Neurol Sci, Palo Alto, CA USA. [Arsava, Ethem M.; Ay, Hakan] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Calvet, David; Mas, Jean-Louis] Paris Descartes Univ, Hop St Anne, Dept Neurol, Paris, France. [Coutts, Shelagh B.; Demchuk, Andrew M.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci & Radiol, Calgary, AB, Canada. [Cucchiara, Brett L.] Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Giles, Matthew F.; Rothwell, Peter M.] John Radcliffe Hosp, Stroke Prevent Res Unit, Oxford OX3 9DU, England. [Purroy, Francisco] Hosp Univ Arnau Vilanova Lleida, Stroke Unit, Dept Neurol, Lleida, Spain. [Purroy, Francisco] Biomed Res Inst Lleida, Lleida, Spain. [Saver, Jeffrey L.] UCLA, Stroke Ctr, Dept Neurol, Los Angeles, CA USA. [Sharma, Vijay K.] Natl Univ Singapore, Div Neurol, YLL Sch Med, Singapore 117548, Singapore. [Sharma, Vijay K.] Natl Univ Singapore Hosp, Singapore, Singapore. [Tsivgoulis, Georgios] Univ Athens, Sch Med, Dept Neurol 2, GR-11527 Athens, Greece. [Tsivgoulis, Georgios] St Annes Univ Hosp Brno, Int Clin Res Ctr, Dept Neurol, Brno, Czech Republic. [Tsivgoulis, Georgios] Democritus Univ Thrace, Dept Neurol, Alexandroupolis, Greece. RP Kelly, PJ (reprint author), Mater Univ Hosp, Neurovasc Unit Translat & Therapeut Res, Nelson St, Dublin 7, Ireland. EM pjkelly@partners.org RI Merwick, Aine/L-9754-2013 OI Saver, Jeffrey/0000-0001-9141-2251; Merwick, Aine/0000-0001-7533-0117 FU Clinician Scientist Award from the Health Research Board (HRB) of Ireland; HRB; Irish Heart Foundation; National Lottery; National Institute of Health Research (NIHR); Stroke Association; Medical Research Council; Dunhill Medical Trust; NIHR Biomedical Research Center, Oxford; Canadian Institutes for Health Research [MOP-118096]; Heart and Stroke Foundation of Alberta; Northwest Territories and Nunavut, Canada Foundation for Innovation; Alberta Foundation for Health Research; Heart and Stroke Foundation of Canada Distinguished Clinician Scientist award; Canadian Institutes of Health Research Institute of Circulatory and Respiratory Health and AstraZeneca Canada Inc; Alberta Heritage Foundation for Medical Research; Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III: FIS [PIO81398]; National Institutes of Health (NIH) [ROI-N5059710]; European Regional Development Fund - Project FNUSA-ICRC [CZ.1.05/1.1.00/02.0123]; St. Annes University Hospital in Brno International Clinical Research Centre; American Heart Association; NIH [ROI-NS61572]; Clinician Scientist Award from National Medical Research Council, Singapore; Lundbeck; Pfizer; Boehringer Ingelheim; Neurovascular Unit for Translational and Therapeutics Research; Takeda FX Dr Kelly is the recipient of a Clinician Scientist Award from the Health Research Board (HRB) of Ireland. A. Merwick was supported by the HRB. Funding was also provided by the Irish Heart Foundation, and National Lottery. P. M. Rothwell and M. Giles received funding from the National Institute of Health Research (NIHR) and the Oxford Vascular Study is funded by the Stroke Association, Medical Research Council, Dunhill Medical Trust and the NIHR Biomedical Research Center, Oxford. Drs Coutts and Demchuk and the vascular imaging of acute stroke for identifying predictors of clinical outcome and recurrent ischemic events (VISION) study were supported by grant funding from the Canadian Institutes for Health Research (MOP-118096) and Heart and Stroke Foundation of Alberta, Northwest Territories and Nunavut, Canada Foundation for Innovation, and Alberta Foundation for Health Research. Dr Coutts received the Heart and Stroke Foundation of Canada Distinguished Clinician Scientist award, supported by the Canadian Institutes of Health Research Institute of Circulatory and Respiratory Health and AstraZeneca Canada Inc, and salary support from the Alberta Heritage Foundation for Medical Research. Dr Purroy was supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III: FIS Number PIO81398. Dr Ay was supported by National Institutes of Health (NIH) grant ROI-N5059710. Dr Tsivgoulis has been supported by European Regional Development Fund - Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123), St. Annes University Hospital in Brno International Clinical Research Centre. Dr Cucchiara was supported by an American Heart Association Fellow-to-Faculty Award and NIH grant ROI-NS61572. Dr Sharma is recipient of Clinician Scientist Award from National Medical Research Council, Singapore. A. Merwick has received unrestricted educational grants from Lundbeck, Pfizer, and Boehringer Ingelheim to attend conferences. Dr Kelly has received speakers' honoraria from Boehringer Ingelheim, Pfizer, and Bristol Myer Squibb. Pfizer and Servier have provided unrestricted educational grants to the Neurovascular Unit for Translational and Therapeutics Research toward stroke education and research. Dr Saver has been an advisory board member of AGA Medical, Boehringer Ingelheim, Bristol Myer Squibb, CoAxia, Fibro Gen, and Sanofi Aventis, and he has performed consultancy work for ImaRx and received honoraria from Concentric Medical. Dr Coutts has been an advisory board member for Bristol Myer Squibb. Dr Mas has been an advisory board member of Bayer, Boehringer Ingelheim, Bristol Myer Squibb, Daiichi-Sankyo, and Sanofi Aventis and has received speaker fees from AstraZeneca, Pfizer, and Takeda. The other authors report no conflicts. NR 21 TC 31 Z9 33 U1 6 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2013 VL 44 IS 10 BP 2814 EP 2820 DI 10.1161/STROKEAHA.113.001576 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 223TC UT WOS:000324831900038 PM 23908061 ER PT J AU Won, SY Schlunk, F Dinkel, J Karatas, H Leung, W Hayakawa, K Lauer, A Steinmetz, H Lo, EH Foerch, C Gupta, R AF Won, Sae-Yeon Schlunk, Frieder Dinkel, Julien Karatas, Hulya Leung, Wendy Hayakawa, Kazuhide Lauer, Arne Steinmetz, Helmuth Lo, Eng H. Foerch, Christian Gupta, Rajiv TI Imaging of Contrast Medium Extravasation in Anticoagulation-Associated Intracerebral Hemorrhage With Dual-Energy Computed Tomography SO STROKE LA English DT Article DE anticoagulation; contrast extravasation; dabigatran; dual-energy CT; hematoma expansion; intracerebral hemorrhage; PCC treatment; warfarin ID THROMBIN INHIBITOR DABIGATRAN; ANGIOGRAPHY SPOT SIGN; ATRIAL-FIBRILLATION; HEMATOMA EXPANSION; PROTHROMBIN COMPLEX; FACTOR-VII; WARFARIN; VOLUME; REVERSAL; THERAPY AB Background and Purpose Contrast medium extravasation (CE) in intracerebral hemorrhage (ICH) is a marker of ongoing bleeding and a predictor of hematoma expansion. The aims of the study were to establish an ICH model in which CE can be quantified, characterized in ICH during warfarin and dabigatran anticoagulation, and to evaluate effects of prothrombin complex concentrates on CE in warfarin-associated ICH. Methods CD1-mice were pretreated orally with warfarin, dabigatran, or vehicle. Prothrombin complex concentrates were administered in a subgroup of warfarin-treated mice. ICH was induced by stereotactic injection of collagenase VIIs into the right striatum. Contrast agent (350 L Isovue 370 mg/mL) was injected intravenously after ICH induction (2-3.5 hours). Thirty minutes later, mice were euthanized, and CE was measured by quantifying the iodine content in the hematoma using dual-energy computed tomography. Results The optimal time point for contrast injection was found to be 3 hours after ICH induction, allowing detection of both an increase and a decrease of CE using dual-energy computed tomography. CE was higher in the warfarin group compared with the controls (P=0.002). There was no significant difference in CE between dabigatran-treated mice and controls. CE was higher in the sham-treated warfarin group than in the prothrombin complex concentrates-treated warfarin group (P<0.001). Conclusions Dual-energy computed tomography allows quantifying CE, as a marker of ongoing bleeding, in a model of anticoagulation-associated ICH. Dabigatran induces less CE in ICH than warfarin and consequently reduces risks of hematoma expansion. This constitutes a potential safety advantage of dabigatran over warfarin. Nevertheless, in case of warfarin anticoagulation, prothrombin complex concentrates reduce this side effect. C1 [Won, Sae-Yeon; Schlunk, Frieder; Lauer, Arne; Steinmetz, Helmuth; Foerch, Christian] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany. [Won, Sae-Yeon; Schlunk, Frieder; Karatas, Hulya; Leung, Wendy; Hayakawa, Kazuhide; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. [Dinkel, Julien; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Won, SY (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany. EM wsy870923@hotmail.com RI Karatas, Hulya/J-1459-2013 OI Karatas, Hulya/0000-0003-4838-6320 FU DARPA AXiS program [N66001-11-4204]; Siemens Medical Solutions; [1300217190] FX This study was supported, in part, by the DARPA AXiS program, Grant Number: N66001-11-4204, P.R. Number: 1300217190, and by a research grant from Siemens Medical Solutions. NR 42 TC 9 Z9 9 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2013 VL 44 IS 10 BP 2883 EP 2890 DI 10.1161/STROKEAHA.113.001224 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 223TC UT WOS:000324831900048 PM 23920016 ER PT J AU Woo, D Rosand, J Kidwell, C McCauley, JL Osborne, J Brown, MW West, SE Rademacher, EW Waddy, S Roberts, JN Koch, S Gonzales, NR Sung, G Kittner, SJ Birnbaum, L Frankel, M Testai, FD Hall, CE Elkind, MS Flaherty, M Coull, B Chong, JY Warwick, T Malkoff, M James, ML Ali, LK Worrall, BB Jones, F Watson, T Leonard, A Martinez, R Sacco, RI Langefeld, CD AF Woo, Daniel Rosand, Jonathan Kidwell, Chelsea McCauley, Jacob L. Osborne, Jennifer Brown, Mark W. West, Sandra E. Rademacher, Eric W. Waddy, Salina Roberts, Jamie N. Koch, Sebastian Gonzales, Nicole R. Sung, Gene Kittner, Steven J. Birnbaum, Lee Frankel, Michael Testai, Fernando Daniel Hall, Christiana E. Elkind, Mitchell S. V. Flaherty, Matthew Coull, Bruce Chong, Ji Y. Warwick, Tanya Malkoff, Marc James, Michael L. Ali, Latisha K. Worrall, Bradford B. Jones, Floyd Watson, Tiffany Leonard, Anne Martinez, Rebecca Sacco, Ralph I. Langefeld, Carl D. TI The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol SO STROKE LA English DT Article DE cerebral hemorrhage; genetics; genomics; hypertension; minority groups; risk factors; stroke ID QUALITY-OF-LIFE; COGNITIVE STATUS; STROKE; ADMIXTURE; BLACKS; WHITES; RISK; EUROQOL; PANEL AB Background and Purpose Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH. Methods The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case-control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (5 years), race, ethnicity, sex, and metropolitan region. Results As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation. Conclusions The ERICH study is a large, case-control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH. C1 [Woo, Daniel; Osborne, Jennifer; Frankel, Michael] Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kidwell, Chelsea] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [McCauley, Jacob L.; West, Sandra E.] Univ Miami, John P Hussman Inst Human Genom, Coral Gables, FL 33124 USA. [Brown, Mark W.; Langefeld, Carl D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Rademacher, Eric W.] Univ Cincinnati, Inst Policy Res, Cincinnati, OH 45267 USA. [Waddy, Salina; Roberts, Jamie N.] NINDS, Bethesda, MD 20892 USA. [Koch, Sebastian; Sacco, Ralph I.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Gonzales, Nicole R.; Martinez, Rebecca] Univ Texas Med Sch Houston, Houston, TX USA. [Sung, Gene] Univ So Calif, Neurocrit Care & Stroke Div, Los Angeles, CA USA. [Koch, Sebastian] Univ Maryland, Baltimore Vet Adm Med Ctr, Baltimore, MD 21201 USA. [Birnbaum, Lee; Jones, Floyd; Leonard, Anne] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Flaherty, Matthew] Emory Univ, Grady Mem Hosp, Atlanta, GA 30322 USA. [Testai, Fernando Daniel] Univ Illinois, Chicago Med Ctr, Chicago, IL 60680 USA. [Hall, Christiana E.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Elkind, Mitchell S. V.] Columbia Univ, New York, NY USA. [Coull, Bruce] Univ Arizona, Tucson, AZ USA. [Chong, Ji Y.] St Lukes Roosevelt Hosp, New York, NY USA. [Warwick, Tanya] Univ Calif San Francisco, Fresno, CA USA. [Malkoff, Marc] Univ New Mexico, Albuquerque, NM 87131 USA. [James, Michael L.] Duke Univ, Dept Anesthesiol, Durham, NC USA. [Ali, Latisha K.] Univ Calif Los Angeles, Los Angeles, CA USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. [Watson, Tiffany] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Woo, D (reprint author), Univ Cincinnati, Coll Med, Dept Neurol, 260 Stetson St ML 0525, Cincinnati, OH 45267 USA. EM Daniel.woo@uc.edu FU National Institute of Neurological Disorders and Stroke [NINDS: U-01-NS069763] FX This study was supported by a grant from the National Institute of Neurological Disorders and Stroke (NINDS: U-01-NS069763). This report does not represent the official view of NINDS, the National Institutes of Health (NIH), or any part of the US Federal Government. No official support or endorsement of this article by NINDS or NIH is intended or should be inferred. NR 23 TC 16 Z9 16 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2013 VL 44 IS 10 BP E120 EP E125 DI 10.1161/STROKEAHA.113.002332 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 223TC UT WOS:000324831900001 PM 24021679 ER PT J AU Erstad, DJ Cusack, JC AF Erstad, Derek J. Cusack, James C., Jr. TI Targeting the NF-kappa B Pathway in Cancer Therapy SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE NF-kappa B inhibitor; IKK inhibitor; Targeting NF-kappa B; Chemoresistance; Radioresistance; Apoptosis ID TUMOR-NECROSIS-FACTOR; SQUAMOUS-CELL-CARCINOMA; UBIQUITIN-PROTEASOME PATHWAY; ENDOTHELIAL GROWTH-FACTOR; ALPHA-INDUCED APOPTOSIS; MULTIPLE-MYELOMA CELLS; RANDOMIZED PHASE-II; GLUCOCORTICOID-RECEPTOR-ALPHA; CHRONIC LYMPHOCYTIC-LEUKEMIA; HEME OXYGENASE-1 EXPRESSION AB Most NF-kappa B inhibitors target the IKK complex, IKB proteins, or NF-kappa B transcription factors. The most promising classes of inhibitors include antioxidants, antiinflammatory compounds, natural compounds, statins, proteasome inhibitors, IKK beta inhibitors, biologics, gene therapy, and RNA interference. Targeting NF-kappa B is limited by intrinsic pathway complexity, cross-talk with other pathways, a lack of biomarkers, poor drug specificity, drug resistance, and difficulty with drug delivery. Future NF-kappa B targeting will be improved through better understanding of the pathway, more specific inhibitors, and multimodality therapies. C1 [Erstad, Derek J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Cusack, James C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. RP Cusack, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM jcusack@partners.org NR 316 TC 27 Z9 30 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD OCT PY 2013 VL 22 IS 4 BP 705 EP + DI 10.1016/j.soc.2013.06.011 PG 43 WC Oncology; Surgery SC Oncology; Surgery GA 228MK UT WOS:000325190700007 PM 24012396 ER PT J AU Morland, LA Raab, M Mackintosh, MA Rosen, CS Dismuke, CE Greene, CJ Frueh, BC AF Morland, Leslie A. Raab, Michelle Mackintosh, Margaret-Anne Rosen, Craig S. Dismuke, Clara E. Greene, Carolyn J. Frueh, B. Christopher TI Telemedicine: A Cost-Reducing Means of Delivering Psychotherapy to Rural Combat Veterans with PTSD SO TELEMEDICINE AND E-HEALTH LA English DT Article DE medicine; military medicine; telehealth; telepsychiatry ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH-SERVICES; PRIMARY-CARE CLINICS; VIETNAM VETERANS; NONINFERIORITY TRIAL; TELEHEALTH; TELEPSYCHIATRY; ANGER; OUTCOMES; THERAPY AB Background:Although effective psychotherapies for posttraumatic stress disorder (PTSD) exist, high percentages of Veterans in need of services are unable to access them. One particular challenge to providing cost-effective psychological treatments to Veterans with PTSD involves the difficulty and high cost of delivering in-person, specialized psychotherapy to Veterans residing in geographically remote locations. The delivery of these services via clinical videoteleconferencing (CVT) has been presented as a potential solution to this access to care problem.Materials and Methods:This study is a retrospective cost analysis of a randomized controlled trial investigating telemedicine service delivery of an anger management therapy for Veterans with PTSD. The parent trial found that the CVT condition provided clinical results that were comparable to the in-person condition. Several cost outcomes were calculated in order to investigate the clinical and cost outcomes associated with the CVT delivery modality relative to in-person delivery.Results:The CVT condition was significantly associated with lower total costs compared with the in-person delivery condition. The delivery of mental health services via CVT enables Veterans who would not normally receive these services access to empirically based treatments. Additional studies addressing long-term healthcare system costs, indirect cost factors at the patient and societal levels, and the use of CVT in other geographic regions of the United States are needed.Conclusions:The results of this study provide evidence that CVT is a cost-reducing mode of service delivery to Veterans with PTSD relative to in-person delivery. C1 [Morland, Leslie A.; Raab, Michelle; Mackintosh, Margaret-Anne; Greene, Carolyn J.] Dept Vet Affairs Pacific Isl Healthcare Syst, Pacific Isl Div, Natl Ctr PTSD, Honolulu, HI 96819 USA. [Raab, Michelle; Mackintosh, Margaret-Anne] Pacific Hlth Res & Educ Inst, Honolulu, HI USA. [Rosen, Craig S.] Dept Vet Affairs Palo Alto Healthcare Syst, Disseminat & Training Div, Natl Ctr PTSD, Palo Alto, CA USA. [Rosen, Craig S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Dismuke, Clara E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Dept Vet Affairs, Charleston, SC USA. [Dismuke, Clara E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Greene, Carolyn J.] Dept Vet Affairs Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. RP Morland, LA (reprint author), Dept Vet Affairs Pacific Isl Healthcare Syst, Pacific Isl Div, Natl Ctr PTSD, 3375 Koapaka St,Suite I-560, Honolulu, HI 96819 USA. EM Leslie.Morland@va.gov OI Mackintosh, Margaret-Anne/0000-0002-2725-3177 FU Veterans Affairs Health Services and Development [TEL 03-080-3]; Office of Research and Development, Medical Research Service, Department of Veterans Affairs FX This work was partially supported by grant TEL 03-080-3 from the Veterans Affairs Health Services and Development. This work was also supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. L. A. M., Principal Investigator of this study, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 53 TC 16 Z9 16 U1 5 U2 22 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD OCT 1 PY 2013 VL 19 IS 10 BP 754 EP 759 DI 10.1089/tmj.2012.0298 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 227RU UT WOS:000325132300005 PM 23931729 ER PT J AU Kahn, E Sossong, S Goh, A Carpenter, D Goldstein, S AF Kahn, Estelle Sossong, Sarah Goh, Anne Carpenter, Diane Goldstein, Sanford TI Evaluation of Skin Cancer in Northern California Kaiser Permanente's Store-and-Forward Teledermatology Referral Program SO TELEMEDICINE AND E-HEALTH LA English DT Article DE dermatology; telemedicine; teledermatology ID MANAGEMENT; DIAGNOSIS; ACCURACY; TRIAGE AB Objective:To determine whether teledermatology referrals yield a shorter time to biopsy of the most common types of skin cancer versus conventional dermatology referrals.Subjects and Methods:A retrospective chart review was performed of California's Central Valley Kaiser Permanente conventional dermatology or teledermatology referrals that yielded a positive skin cancer biopsy over a 7-month period. Four primary care clinics at Kaiser Permanente's Stockton Medical Center in California's Central Valley were included. Patients who were studied were treated for squamous cell carcinoma of skin, basal cell carcinoma of skin, and malignant melanoma. We compared the time interval between initial evaluation and biopsy of the most common types of skin cancer for teledermatology versus traditional referrals from primary care.Results:Our study criteria were met by 293 patient cases (58% conventional referrals and 42% teledermatology referrals). The mean time to biopsy of skin cancer was 13.8 days for conventional referrals (median, 12.0 days) versus a mean of 9.7 days (median, 9.0 days) for teledermatology referrals (p<0.0001).Conclusions:The use of teledermatology in remote areas results in a shorter time to biopsy than traditional referral methods as a result of improved triaging measures. C1 [Kahn, Estelle] Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. [Sossong, Sarah] Massachusetts Gen Hosp, TeleHlth, Boston, MA 02114 USA. [Goh, Anne] Kaiser Permanente, Dept Internal Med, San Francisco, CA USA. [Goldstein, Sanford] Kaiser Permanente, Dept Dermatol, San Francisco, CA USA. [Carpenter, Diane] Kaiser Permanente, Div Res, San Francisco, CA USA. RP Kahn, E (reprint author), Kaiser Permanente, Dept Dermatol, 280 West MacArthur Blvd, Oakland, CA 94611 USA. EM Estelle.C.Kahn@kp.org NR 11 TC 8 Z9 8 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD OCT 1 PY 2013 VL 19 IS 10 BP 780 EP 785 DI 10.1089/tmj.2012.0260 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 227RU UT WOS:000325132300009 PM 24079264 ER PT J AU Banerjee, A Wang, JM Bodhankar, S Vandenbark, AA Murphy, SJ Offner, H AF Banerjee, Anirban Wang, Jianming Bodhankar, Sheetal Vandenbark, Arthur A. Murphy, Stephanie J. Offner, Halina TI Phenotypic Changes in Immune Cell Subsets Reflect Increased Infarct Volume in Male vs. Female Mice SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Experimental stroke; Gender bias; Immune markers; Activated Tcells; Suppressor Tcells; Ischemia ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FOCAL CEREBRAL-ISCHEMIA; EXPERIMENTAL STROKE; SEX-DIFFERENCES; ALPHA-4 INTEGRIN; MULTIPLE-SCLEROSIS; INFLAMMATORY CELLS; NADPH OXIDASE; BRAIN-INJURY AB Inflammatory responses in the brain after cerebral ischemia have been studied extensively in male mice, but not female mice, thus potentially giving a less-than-accurate view of gender associated pathological processes. In humans, cerebral infarcts are typically smaller in premenopausal females than in age-matched males. In the current study, we confirmed smaller infarcts in female vs. male mice after middle cerebral artery occlusion and 96 h of reperfusion. Moreover, we explored immunological alterations related to this difference and found that the percentage of CD4(+) T lymphocytes was significantly higher in spleens in males than females, with increased expression of the activation markers, CD69 and CD44. In contrast, the percentage of CD8(+) T lymphocytes was significantly higher in spleens of females than males, leading to the identification of a small but distinct population of IL-10-secreting CD8(+)CD122(+) suppressor T cells that were also increased in females. Finally, we observed that males have a greater percentage of activated macrophages/microglia in the brain than females, as well as increased expression of the VLA-4 adhesion molecule in both brain and spleen. This new information suggesting gender-dependent immunological mechanisms in stroke implies that effective treatments for human stroke may also be gender specific. C1 [Banerjee, Anirban; Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR USA. [Banerjee, Anirban; Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Wang, Jianming; Murphy, Stephanie J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR USA. EM offnerva@ohsu.edu FU NIH [NS076013]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors wish to thank Dr. Gil Benedek for the helpful discussions and Melissa Barber for the assistance in submitting the manuscript. This work was supported by NIH grant no. NS076013. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 46 TC 21 Z9 21 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 J9 TRANSL STROKE RES JI Transl. Stroke Res. PD OCT PY 2013 VL 4 IS 5 BP 554 EP 563 DI 10.1007/s12975-013-0268-z PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227IN UT WOS:000325106200010 PM 24187596 ER PT J AU Small, AC Tsao, CK Moshier, EL Gartrell, BA Wisnivesky, JP Godbold, J Sonpavde, G Palese, MA Hall, SJ Oh, WK Galsky, MD AF Small, Alexander C. Tsao, Che-Kai Moshier, Erin L. Gartrell, Benjamin A. Wisnivesky, Juan P. Godbold, James Sonpavde, Guru Palese, Michael A. Hall, Simon J. Oh, William K. Galsky, Matthew D. TI Trends and variations in utilization of nephron-sparing procedures for stage I kidney cancer in the United States SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Renal surgery; Nephrectomy; Nephron-sparing surgery; Kidney cancer ID RENAL-CELL CARCINOMA; RADICAL NEPHRECTOMY; DATA-BASE; TUMORS; OUTCOMES; SURVIVAL; MORTALITY; SURGERY; IMPACT; MASSES AB The incidental detection of early-stage kidney tumors is increasing in the United States. Nephron-sparing approaches (NS) to managing these tumors are equivalent to radical nephrectomy (RN) in oncologic outcomes and have a decreased impact on renal function. Our objective was to evaluate trends in the use of NS over the past decade and the socioeconomic factors associated with its use. The National Cancer Database was queried to identify patients with stage I kidney cancer between 2000 and 2008. Patients were classified by the type of surgery as NS (local destruction and local excision) or RN. Patients were further categorized by age, race, insurance status, and income. Log-binomial regression was used to estimate prevalence ratios (PR) for the proportion of NS to RN according to demographic and socioeconomic characteristics. From 2000 to 2008, there were 142,194 cases of kidney cancer reported to the NCDB. In these cases, 43,034 (30.3 %) patients had NS, and 86,431 (60.78 %) patients had RN. The prevalence of NS increased 10 % per year (PR = 1.10, p < 0.0001)-from 20.0 % in 2000 to 45.1 % in 2008. Older age, lower income, Black race, Hispanic ethnicity, and lack of health insurance were associated with a decreased prevalence of NS. NS as a treatment for stage I kidney cancer has increased steadily since 2000. Age, racial, and socioeconomic differences may exist in the utilization of NS. Additional analyses, with patient level data, are required to address the independent significance of these variables in an effort to develop strategies to mitigate these potential disparities. C1 [Small, Alexander C.; Tsao, Che-Kai; Moshier, Erin L.; Gartrell, Benjamin A.; Godbold, James; Oh, William K.; Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. [Wisnivesky, Juan P.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Wisnivesky, Juan P.] Mt Sinai Sch Med, Div Pulm & Crit Care Med, New York, NY 10029 USA. [Sonpavde, Guru] Texas Oncol, Houston, TX USA. [Sonpavde, Guru] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Med Oncol, Houston, TX 77030 USA. [Palese, Michael A.; Hall, Simon J.] Mt Sinai Sch Med, Dept Urol, New York, NY 10029 USA. RP Galsky, MD (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu FU Doris Duke Charitable Foundation FX Source of Funding: Doris Duke Charitable Foundation. NR 29 TC 6 Z9 6 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD OCT PY 2013 VL 31 IS 5 BP 1211 EP 1217 DI 10.1007/s00345-012-0873-6 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 226HJ UT WOS:000325025500030 PM 22622394 ER PT J AU Nowak, N Szopa, M Thanabalasingham, G McDonald, TJ Colclough, K Skupien, J James, TJ Kiec-Wilk, B Kozek, E Mlynarski, W Hattersley, AT Owen, KR Malecki, MT AF Nowak, Natalia Szopa, Magdalena Thanabalasingham, Gaya McDonald, Tim J. Colclough, Kevin Skupien, Jan James, Timothy J. Kiec-Wilk, Beata Kozek, Elzbieta Mlynarski, Wojciech Hattersley, Andrew T. Owen, Katharine R. Malecki, Maciej T. TI Cystatin C is not a good candidate biomarker for HNF1A-MODY SO ACTA DIABETOLOGICA LA English DT Article DE Monogenic diabetes; MODY; Cystatin C; HNF1A ID GLOMERULAR-FILTRATION-RATE; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; MUTATIONS; GENE; GLUCOSE; MODY3 AB Cystatin C is a marker of glomerular filtration rate (GFR). Its level is influenced, among the others, by CRP whose concentration is decreased in HNF1A-MODY. We hypothesized that cystatin C level might be altered in HNF1A-MODY. We aimed to evaluate cystatin C in HNF1A-MODY both as a diagnostic marker and as a method of assessing GFR. We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland. Subjects from two UK centres were used as replication panels: including 215 HNF1A-MODY, 203 T2DM, 39 HNF4A-MODY, 170 GCK-MODY, 17 HNF1B-MODY and 58 T1DM patients. The data were analysed with additive models, adjusting for gender, age, BMI and estimated GFR (creatinine). In the Polish subjects, adjusted cystatin C level in HNF1A-MODY was lower compared with T1DM, T2DM and ND (p < 0.05). Additionally, cystatin C-based GFR was higher than that calculated from creatinine level (p < 0.0001) in HNF1A-MODY, while the two GFR estimates were similar or cystatin C-based lower in the other groups. In the UK subjects, there were no differences in cystatin C between HNF1A-MODY and the other diabetic subgroups, except HNF1B-MODY. In UK HNF1A-MODY, cystatin C-based GFR estimate was higher than the creatinine-based one (p < 0.0001). Concluding, we could not confirm our hypothesis (supported by the Polish results) that cystatin C level is altered by HNF1A mutations; thus, it cannot be used as a biomarker for HNF1A-MODY. In HNF1A-MODY, the cystatin C-based GFR estimate is higher than the creatinine-based one. C1 [Nowak, Natalia; Szopa, Magdalena; Kiec-Wilk, Beata; Kozek, Elzbieta; Malecki, Maciej T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. [Szopa, Magdalena] Jagiellonian Univ, Coll Med, Dept Med Educ, PL-31501 Krakow, Poland. [Szopa, Magdalena; Kiec-Wilk, Beata; Kozek, Elzbieta; Malecki, Maciej T.] Univ Hosp, Krakow, Poland. [Thanabalasingham, Gaya; Owen, Katharine R.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Thanabalasingham, Gaya; Colclough, Kevin; Owen, Katharine R.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [McDonald, Tim J.; Hattersley, Andrew T.] Univ Exeter, Peninsula Coll Med & Dent, NIHR Clin Res Facil, Exeter, Devon, England. [Skupien, Jan] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [James, Timothy J.] John Radcliffe Hosp, Dept Clin Biochem, Oxford OX3 9DU, England. [Mlynarski, Wojciech] Med Univ Lodz, Dept Paediat Oncol Hematol & Diabetol, Lodz, Poland. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland. EM malecki_malecki@yahoo.com OI McDonald, Timothy/0000-0003-3559-6660; Hattersley, Andrew/0000-0001-5620-473X FU EU Framework 7 CEED3 grant [HEALTH-F2-2008-223211]; Jagiellonian University Medical College (MTM); Oxford NIHR Biomedical Research Centre; National Institute for Health Research; Polish Ministry of Science and Higher Education; TEAM Programme FX We thank the families participating in the study. This study was supported by the EU Framework 7 CEED3 grant (HEALTH-F2-2008-223211), by funds from the Jagiellonian University Medical College (MTM) and by the Oxford NIHR Biomedical Research Centre. KRO is a National Institute for Health Research-funded Clinician Scientist. MS is funded by the habilitation grant of the Polish Ministry of Science and Higher Education. WM is funded by the TEAM Programme coordinated by the Foundation for Polish Science. NR 18 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD OCT PY 2013 VL 50 IS 5 BP 815 EP 820 DI 10.1007/s00592-012-0378-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 226HV UT WOS:000325026900021 PM 22350134 ER PT J AU Leijenaar, RTH Carvalho, S Velazquez, ER Van Elmpt, WJC Parmar, C Hoekstra, OS Hoekstra, CJ Boellaard, R Dekker, ALAJ Gillies, RJ Aerts, HJWL Lambin, P AF Leijenaar, Ralph T. H. Carvalho, Sara Velazquez, Emmanuel Rios Van Elmpt, Wouter J. C. Parmar, Chintan Hoekstra, Otto S. Hoekstra, Corneline J. Boellaard, Ronald Dekker, Andre L. A. J. Gillies, Robert J. Aerts, Hugo J. W. L. Lambin, Philippe TI Stability of FDG-PET Radiomics features: An integrated analysis of test-retest and inter-observer variability SO ACTA ONCOLOGICA LA English DT Article ID CELL LUNG-CANCER; STANDARDIZED UPTAKE VALUE; RESPONSE ASSESSMENT; TEXTURAL FEATURES; F-18-FDG PET; RADIOTHERAPY; IMAGES; TUMOR; REPEATABILITY; CT AB Purpose. Besides basic measurements as maximum standardized uptake value (SUV)(max) or SUVmean derived from 18F-FDG positron emission tomography (PET) scans, more advanced quantitative imaging features (i.e. "Radiomics" features) are increasingly investigated for treatment monitoring, outcome prediction, or as potential biomarkers. With these prospected applications of Radiomics features, it is a requisite that they provide robust and reliable measurements. The aim of our study was therefore to perform an integrated stability analysis of a large number of PET-derived features in non-small cell lung carcinoma (NSCLC), based on both a test-retest and an inter-observer setup. Methods. Eleven NSCLC patients were included in the test-retest cohort. Patients underwent repeated PET imaging within a one day interval, before any treatment was delivered. Lesions were delineated by applying a threshold of 50% of the maximum uptake value within the tumor. Twenty-three NSCLC patients were included in the inter-observer cohort. Patients underwent a diagnostic whole body PET-computed tomography (CT). Lesions were manually delineated based on fused PET-CT, using a standardized clinical delineation protocol. Delineation was performed independently by five observers, blinded to each other. Fifteen first order statistics, 39 descriptors of intensity volume histograms, eight geometric features and 44 textural features were extracted. For every feature, test-retest and inter-observer stability was assessed with the intra-class correlation coefficient (ICC) and the coefficient of variability, normalized to mean and range. Similarity between test-retest and inter-observer stability rankings of features was assessed with Spearman's rank correlation coefficient. Results. Results showed that the majority of assessed features had both a high test-retest (71%) and inter-observer (91%) stability in terms of their ICC. Overall, features more stable in repeated PET imaging were also found to be more robust against inter-observer variability. Conclusion. Results suggest that further research of quantitative imaging features is warranted with respect to more advanced applications of PET imaging as being used for treatment monitoring, outcome prediction or imaging biomarkers. C1 [Leijenaar, Ralph T. H.; Carvalho, Sara; Velazquez, Emmanuel Rios; Van Elmpt, Wouter J. C.; Parmar, Chintan; Dekker, Andre L. A. J.; Aerts, Hugo J. W. L.; Lambin, Philippe] MUMC, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands. [Hoekstra, Otto S.; Boellaard, Ronald] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands. [Hoekstra, Corneline J.] Jeroen Bosch Med Ctr, Dept Nucl Med, Shertogenbosch, Netherlands. [Gillies, Robert J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Imaging & Metab, Tampa, FL 33612 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol,Med Sch, Boston, MA 02115 USA. RP Leijenaar, RTH (reprint author), MAASTRO Clin, Dr Tanslaan 12, NL-6229 ET Maastricht, Netherlands. EM ralph.leijenaar@maastro.nl RI Aerts, Hugo/P-6350-2015; OI Aerts, Hugo/0000-0002-2122-2003; Dekker, Andre/0000-0002-0422-7996; Gillies, Robert/0000-0002-8888-7747; Boellaard, Ronald/0000-0002-0313-5686 FU QuIC-ConCePT project; EFPI A companies; Innovative Medicine Initiative Joint Undertaking (IMI JU) [115151]; National Institute of Health [NIH-USA U01 CA 143062-01]; CTMM framework (AIRFORCE project) [030-103]; EU; euroCAT; Kankeronderzoekfonds Limburg from the Health Foundation Limburg; Dutch Cancer Society [KWF UM 2011-5020, KWF UM 2009-4454] FX Authors acknowledge financial support from the QuIC-ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. Authors also acknowledge financial support from the National Institute of Health (NIH-USA U01 CA 143062-01, Radiomics of NSCLC), the CTMM framework (AIRFORCE project, grant 030-103), EU 6th and 7th framework program (EUROXY, METOXIA, EURECA, ART-FORCE), euroCAT (IVA Interreg-www.eurocat.info), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2011-5020, KWF UM 2009-4454). NR 25 TC 60 Z9 61 U1 7 U2 28 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD OCT PY 2013 VL 52 IS 7 BP 1391 EP 1397 DI 10.3109/0284186X.2013.812798 PG 7 WC Oncology SC Oncology GA 223AU UT WOS:000324776100020 PM 24047337 ER PT J AU Carvalho, S Leijenaar, RTH Velazquez, ER Oberije, C Parmar, C Van Elmpt, W Reymen, B Troost, EGC Oellers, M Dekker, A Gillies, R Aerts, HJWL Lambin, P AF Carvalho, Sara Leijenaar, Ralph T. H. Velazquez, Emmanuel Rios Oberije, Cary Parmar, Chintan Van Elmpt, Wouter Reymen, Bart Troost, Esther G. C. Oellers, Michel Dekker, Andre Gillies, Robert Aerts, Hugo J. W. L. Lambin, Philippe TI Prognostic value of metabolic metrics extracted from baseline positron emission tomography images in non-small cell lung cancer SO ACTA ONCOLOGICA LA English DT Article ID SOLID TUMORS; PET; VOLUME; SURVIVAL; QUANTIFICATION; RADIOTHERAPY; PREDICTION; IMPACT AB Background. Maximum, mean and peak SUV of primary tumor at baseline FDG-PET scans, have often been found predictive for overall survival in non-small cell lung cancer (NSCLC) patients. In this study we further investigated the prognostic power of advanced metabolic metrics derived from intensity volume histograms (IVH) extracted from PET imaging. Methods. A cohort of 220 NSCLC patients (mean age, 66.6 years; 149 men, 71 women), stages I-IIIB, treated with radiotherapy with curative intent were included (NCT00522639). Each patient underwent standardized pre-treatment CT-PET imaging. Primary GTV was delineated by an experienced radiation oncologist on CT-PET images. Common PET descriptors such as maximum, mean and peak SUV, and metabolic tumor volume (MTV) were quantified. Advanced descriptors of metabolic activity were quantified by IVH. These comprised five groups of features: absolute and relative volume above relative intensity threshold (AVRI and RVRI), absolute and relative volume above absolute intensity threshold (AVAI and RVAI), and absolute intensity above relative volume threshold (AIRV). MTV was derived from the IVH curves for volumes with SUV above 2.5, 3 and 4, and of 40% and 50% maximum SUV. Univariable analysis using Cox Proportional Hazard Regression was performed for overall survival assessment. Results. Relative volume above higher SUV (80%) was an independent predictor of OS (p = 0.05). None of the possible surrogates for MTV based on volumes above SUV of 3, 40% and 50% of maximum SUV showed significant associations with OS [p (AVAI(3)) = 0.10, p (AVAI(4)) = 0.22, p (AVRI(40%)) = 0.15, p (AVRI(50%)) = 0.17]. Maximum and peak SUV (r = 0.99) revealed no prognostic value for OS [p (maximum SUV) = 0.20, p (peak SUV) = 0.22]. Conclusions. New methods using more advanced imaging features extracted from PET were analyzed. Best prognostic value for OS of NSCLC patients was found for relative portions of the tumor above higher uptakes (80% SUV). C1 [Carvalho, Sara; Leijenaar, Ralph T. H.; Velazquez, Emmanuel Rios; Oberije, Cary; Parmar, Chintan; Van Elmpt, Wouter; Reymen, Bart; Troost, Esther G. C.; Oellers, Michel; Dekker, Andre; Aerts, Hugo J. W. L.; Lambin, Philippe] MUMC, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol,Med Sch, Boston, MA 02115 USA. [Gillies, Robert] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Imaging & Metab, Tampa, FL 33612 USA. [Gillies, Robert] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Radiol, Tampa, FL 33612 USA. RP Carvalho, S (reprint author), Maastricht Univ Med Ctr, Dept Radiat Oncol, MAASTRO Clin, GROW Sch Oncol & Dev Biol, Dr Tanslaan 12, NL-6229 ET Maastricht, Netherlands. EM sara.carvalho@maastro.nl RI Oberije, Cary/I-4018-2013; Aerts, Hugo/P-6350-2015; OI Oberije, Cary/0000-0003-0749-5117; Aerts, Hugo/0000-0002-2122-2003; Dekker, Andre/0000-0002-0422-7996; Troost, Esther/0000-0001-9550-9050 FU QuIC - ConCePT project; EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) [115151]; National Institute of Health [NIH-USA U01 CA 143062-01]; CTMM framework (AIRFORCE project) [030-103]; EU; euroCAT; Kankeronderzoekfonds Limburg from the Health Foundation Limburg; Dutch Cancer Society [KWF UM 2011-5020, KWF UM 2009-4454] FX We acknowledge financial support from the QuIC - ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. We also acknowledge financial support from the National Institute of Health (NIH-USA U01 CA 143062-01, Radiomics of NSCLC), the CTMM framework (AIRFORCE project, grant 030-103), EU 6th and 7th framework program (EUROXY, METOXIA, EURECA, ARTFORCE), euroCAT (IVA Interreg-www.eurocat.info), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2011-5020, KWF UM 2009-4454). NR 24 TC 14 Z9 14 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD OCT PY 2013 VL 52 IS 7 BP 1398 EP 1404 DI 10.3109/0284186X.2013.812795 PG 7 WC Oncology SC Oncology GA 223AU UT WOS:000324776100021 PM 24047338 ER PT J AU Quraishi, SA Litonjua, AA Moromizato, T Gibbons, FK Camargo, CA Giovannucci, E Christopher, KB AF Quraishi, Sadeq A. Litonjua, Augusto A. Moromizato, Takuhiro Gibbons, Fiona K. Camargo, Carlos A., Jr. Giovannucci, Edward Christopher, Kenneth B. TI Association between prehospital vitamin D status and hospital-acquired bloodstream infections SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CARE-ASSOCIATED INFECTIONS; LOCALLY WEIGHTED REGRESSION; CRITICALLY-ILL PATIENTS; D DEFICIENCY; UNITED-STATES; HEALTH; RISK; INSUFFICIENCY; INITIATIVES; COMORBIDITY AB Background: Alterations in immune function can predispose patients to nosocomial infections. Few studies have explored potentially modifiable host factors that may improve immune function and decrease risk of hospital-acquired bloodstream infection (HABSI). Vitamin D is a key regulator of innate and adaptive immune systems that may influence host susceptibility to infections. Objective: We investigated the association between prehospital serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of HABSI. Design: We performed a retrospective cohort study of 2135 adult patients from 2 Boston teaching hospitals. All patients had 25(OH)D concentrations measured before hospitalization between 1993 and 2010. The main outcome measure was HABSI, which was defined as positive blood cultures from samples drawn 48 h after hospital admission. Coagulase-negative Staphylococcus isolates were not considered to be bloodstream infections. Associations between 25(OH)D groups and HABSI were estimated by using bivariable and multivariable logistic regression models. Adjusted ORs were estimated with the inclusion of covariate terms thought to plausibly interact with both 25(OH)D concentration and HABSI. Results: Compared with patients with 25(OH)D concentrations >= 30 ng/mL, patients with concentrations <30 ng/mL had higher odds of HABSI. For 25(OH)D concentrations <10 ng/mL, the OR was 2.33 (95% CI: 1.45, 3.74); for 25(OH)D concentrations from 10 to 19.9 ng/mL, the OR was 1.60 (95% CI: 1.04, 2.46); and for 25(OH)D concentrations from 20 to 29.9 ng/mL, the OR was 1.13 (95% CI: 0.69, 1.84). After adjustment for age, sex, race (nonwhite compared with white), patient type (medical compared with surgical), and Deyo-Charlson index, the ORs of HABSI were 1.95 (95% CI: 1.22, 3.12), 1.36 (95% CI: 0.89, 2.07), and 0.98 (95% CI: 0.60, 1.62), respectively. Conclusions: The analysis of 2135 adult patients showed that 25(OH)D concentrations <10 ng/mL before hospitalization were associated with significantly increased odds of developing HABSI. These data support the initiation of randomized trials to test the role of vitamin D supplementation in HABSI prevention. C1 [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Litonjua, Augusto A.; Gibbons, Fiona K.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Litonjua, Augusto A.; Gibbons, Fiona K.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Div Renal, Nathan Hellman Mem Lab, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org OI Litonjua, Augusto/0000-0003-0422-5875 FU NIH [5T32GM007592-33, UL1 RR025758, R01 AI093723, U01 AI087881, K08AI060881] FX Supported by the NIH [5T32GM007592-33 and UL1 RR025758 (to SAQ); R01 AI093723 and U01 AI087881 (to CAC); and K08AI060881 (to KBC)]. NR 54 TC 25 Z9 26 U1 1 U2 6 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2013 VL 98 IS 4 BP 952 EP 959 DI 10.3945/ajcn.113.058909 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 221YF UT WOS:000324696100013 PM 23945717 ER PT J AU Franciosa, M Mashimo, H AF Franciosa, Mark Mashimo, Hiroshi TI Stretta Radiofrequency Treatment for GERD: A Safe and Effective Modality SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID GASTROESOPHAGEAL-REFLUX DISEASE; LOWER ESOPHAGEAL SPHINCTER; ENERGY DELIVERY; ACID EXPOSURE; SYMPTOMS; TRIAL C1 [Franciosa, Mark; Mashimo, Hiroshi] Harvard Univ, Ctr Swallowing & Motil Disorders, VA Boston Healthcare Syst, Sch Med,Gastroenterol Sect, Boston, MA 02130 USA. RP Mashimo, H (reprint author), Harvard Univ, Ctr Swallowing & Motil Disorders, Brigham & Womens Hosp,Sch Med, VA Boston Healthcare Syst,Gastroenterol Sect 111, 150 South Huntington Ave, Boston, MA 02130 USA. EM hmashimo@hms.harvard.edu NR 10 TC 4 Z9 4 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 IS 10 BP 1654 EP 1655 DI 10.1038/ajg.2013.275 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229OI UT WOS:000325276100016 PM 24091508 ER PT J AU Gerson, LB Vela, MF Katz, PO AF Gerson, Lauren B. Vela, Marcelo F. Katz, Philip O. TI Stretta For Refractory GERD: Now More Than Ever Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID GASTROESOPHAGEAL-REFLUX DISEASE; RADIOFREQUENCY ENERGY; SHAM; SYMPTOMS; TRIAL C1 [Gerson, Lauren B.] Stanford Univ, Div Gastroenterol & Hepatol, Redwood City, CA 94063 USA. [Vela, Marcelo F.] Baylor Coll Med, Houston, TX 77030 USA. [Vela, Marcelo F.] ME DeBakey VA Med Ctr, Houston, TX USA. [Katz, Philip O.] Albert Einstein Med Ctr, Dept Gastroenterol, Philadelphia, PA 19141 USA. RP Gerson, LB (reprint author), Stanford Univ, Div Gastroenterol & Hepatol, 450 Broadway St,Pavil C,Mail Code 5241, Redwood City, CA 94063 USA. EM lgersonmd@yahoo.com NR 9 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 IS 10 BP 1656 EP 1657 DI 10.1038/ajg.2013.283 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229OI UT WOS:000325276100018 PM 24091510 ER PT J AU Vela, MF Gerson, LB Katz, PO AF Vela, Marcelo F. Gerson, Lauren B. Katz, Philip O. TI Non-Erosive Reflux Disease is More Complex Than Negative Endoscopy Only Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID GASTROESOPHAGEAL-REFLUX; FUNDOPLICATION; INDEX C1 [Vela, Marcelo F.] Baylor Coll Med, Div Gastroenterol & Hepatol, Houston, TX 77030 USA. [Vela, Marcelo F.] ME DeBakey VA Med Ctr, Houston, TX USA. [Gerson, Lauren B.] Stanford Univ, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA. [Katz, Philip O.] Albert Einstein Med Ctr, Dept Gastroenterol, Philadelphia, PA 19141 USA. RP Vela, MF (reprint author), Baylor Coll Med, Div Gastroenterol, 1 Baylor Plaza,BCM 901, Houston, TX 77030 USA. EM mvela@bcm.edu NR 11 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 IS 10 BP 1658 EP 1659 DI 10.1038/ajg.2013.284 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229OI UT WOS:000325276100020 PM 24091512 ER PT J AU Carter, CE Katz, R Kramer, H de Boer, IH Kestenbaum, BR Peralta, CA Siscovick, D Sarnak, MJ Levey, AS Inker, LAS Allison, MA Criqui, MH Shlipak, MG Ix, JH AF Carter, Caitlin E. Katz, Ronit Kramer, Holly de Boer, Ian H. Kestenbaum, Bryan R. Peralta, Carmen A. Siscovick, David Sarnak, Mark J. Levey, Andrew S. Inker, Lesley A. S. Allison, Matthew A. Criqui, Michael H. Shlipak, Michael G. Ix, Joachim H. TI Influence of Urine Creatinine Concentrations on the Relation of Albumin-Creatinine Ratio With Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Urine creatinine concentration; cardiovascular disease events ID GLOMERULAR-FILTRATION-RATE; NONDIABETIC INDIVIDUALS; SERUM CREATININE; BLOOD-PRESSURE; EXCRETION RATE; COOKED MEAT; RISK; MORTALITY; HEART; METAANALYSIS AB Background: Higher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. Urine creatinine excretion is correlated with muscle mass, and low muscle mass also is associated with CVD. Whether low urine creatinine concentration in the denominator of theACRcontributes to the association of ACR with CVD is uncertain. Study Design: Prospective cohort study. Setting & Participants: 6,770 community-living individuals without CVD. Predictors: Spot urine albumin concentration, the reciprocal of the urine creatinine concentration (1/UCr), and ACR. Outcome: Incident CVD events. Results: During a mean of 7.1 years of follow-up, 281 CVD events occurred. Geometric mean values for spot urine creatinine concentration, urine albumin concentration, and ACR were 95 +/- 2 (SD) mg/dL, 0.7 +/- 3.7 mg/dL, and 7.0 +/- 3.1 mg/g. Urine creatinine concentration was lower in older, female, and low-weight individuals. Adjusted HRs per 2-fold higher increment in each urinary measure with CVD events were similar (1/UCr: 1.07 [95% CI, 0.94-1.22]; urine albumin concentration: 1.08 [95% CI, 1.01-1.14]; and ACR: 1.11 [95% CI, 1.04-1.18]). ACR >= 10 mg/g was associated more strongly with CVD events in individuals with low weight (HR for lowest vs highest tertile: 4.34 vs 1.97; P for interaction = 0.006). Low weight also modified the association of urine albumin concentration with CVD (P for interaction = 0.06), but 1/UCr did not (P for interaction = 0.9). Limitations: We lacked 24-hour urine data. Conclusions: Although ACR is associated more strongly with CVD events in persons with low body weight, this association is not driven by differences in spot urine creatinine concentration. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin concentration and less by urine creatinine concentration. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is aUS Government Work. There are no restrictions on its use. C1 [Carter, Caitlin E.; Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kramer, Holly] Loyola Med Ctr, Dept Med, Div Nephrol & Hypertens, Maywood, IL USA. [de Boer, Ian H.; Kestenbaum, Bryan R.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan R.] Univ Washington, Dept Med, Kidney Res Inst, Seattle, WA USA. [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Sarnak, Mark J.; Levey, Andrew S.; Inker, Lesley A. S.] Tufts Med Ctr, Dept Med, Boston, MA USA. [Allison, Matthew A.; Criqui, Michael H.; Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92161 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu OI Kramer, Holly/0000-0002-6374-837X; Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung and Blood Institute [R01-HL-096851, T32 HL007261, R21HL091217, N01-HC-95159, N01-HC-95166, N01-HC-95169, R01-HL-071739, R01-HL-072403] FX Supported by the National Heart, Lung and Blood Institute (grants R01-HL-096851, T32 HL007261, and R21HL091217 and contracts N01-HC-95159, N01-HC-95166, N01-HC-95169, R01-HL-071739, and R01-HL-072403). NR 25 TC 4 Z9 4 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2013 VL 62 IS 4 BP 722 EP 729 DI 10.1053/j.ajkd.2013.05.010 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 224CB UT WOS:000324858000013 PM 23830183 ER PT J AU Nigwekar, SU Wenger, J Thadhani, R Bhan, I AF Nigwekar, Sagar U. Wenger, Julia Thadhani, Ravi Bhan, Ishir TI Hyponatremia, Mineral Metabolism, and Mortality in Incident Maintenance Hemodialysis Patients: A Cohort Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Sodium; hyponatremia; mortality; mineral bone disease; vitamin D ID SERUM ALKALINE-PHOSPHATASE; CHRONIC HEART-FAILURE; VITAMIN-D; DIALYSIS PATIENTS; SODIUM; SURVIVAL; OUTCOMES; OSTEOPOROSIS; PATTERNS; MARKERS AB Background: Hyponatremia is associated with increased mortality in chronic diseases. Recent animal studies also implicate hyponatremia in bone abnormalities. However, associations between hyponatremia, mineral bone abnormalities, and mortality in incident hemodialysis patients are unknown. Study Design: Nonconcurrent prospective cohort study. Setting & Participants: Incident hemodialysis patients from the Accelerated Mortality on Renal Replacement (ArMORR) cohort with available serum sodium measurements from the time of dialysis therapy initiation (n = 6,127) were classified as hyponatremic (sodium, < 135 mEq/L) or normonatremic (sodium, 135-145 mEq/L) based on glucose-corrected sodium level at the time of dialysis therapy initiation. Patients with sodium levels > 145 mEq/L were excluded (n = 74). Predictor: Hyponatremia (sodium, < 135 mEq/L). Outcomes: Mineral bone abnormalities; rates of falls, fractures, and mortality. Measurements: Hyponatremia and mineral bone abnormalities were assessed at the time of hemodialysis therapy initiation. Data for other outcomes were collected during a 1-year follow-up. Univariate and multivariable logistic and Cox proportion hazard analyses were conducted to compute ORs and HRs, respectively, with 95% CIs. Results: 775 patients were hyponatremic and 5,278 were normonatremic at baseline. In univariate analyses, hyponatremia was associated with hypercalcemia (OR, 1.92; 95% CI, 1.11-3.30), elevated alkaline phosphatase level (OR, 1.36; 95% CI, 1.12-1.66), and hypoparathyroidism (OR, 1.40; 95% CI, 1.18-1.65). Similar relationships were observed in multivariable models. No statistically significant relationships were observed with phosphorus abnormalities, hypovitaminosis D, falls, or fractures. 965 (15.8%) patients had died at the 1-year follow up. Compared with normonatremic patients, hyponatremic patients had higher 1-year mortality in univariate (HR, 1.59; 95% CI, 1.34-1.87) and multivariable analyses (HR, 1.42; 95% CI, 1.19-1.69). Limitations: Low rate of falls and fractures, lack of data for bone density and fibroblast growth factor 23. Conclusions: In incident hemodialysis patients, hyponatremia is associated with hypercalcemia, elevated alkaline phosphatase levels, hypoparathyroidism, and increased 1-year mortality. Future studies are needed to examine whether treatments to alter hyponatremia have effects on mineral bone abnormalities and mortality. (C) 2013 by the National Kidney Foundation, Inc. C1 [Nigwekar, Sagar U.; Wenger, Julia; Thadhani, Ravi; Bhan, Ishir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Nigwekar, Sagar U.] Harvard Univ, Scholars Clin Sci Program, Sch Med, Boston, MA USA. RP Nigwekar, SU (reprint author), Massachusetts Gen Hosp, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM sagarnigs@gmail.com FU Clinical Scientist in Nephrology Fellowship from the American Kidney Fund; Abbott Laboratories FX Support: Dr Nigwekar is supported by the Clinical Scientist in Nephrology Fellowship from the American Kidney Fund.; Financial Disclosure: Dr Thadhani has received a research grant from Abbott Laboratories and is a consultant to FMCNA. The other authors declare that they have no other relevant financial interests. NR 33 TC 18 Z9 18 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2013 VL 62 IS 4 BP 755 EP 762 DI 10.1053/j.ajkd.2013.02.367 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 224CB UT WOS:000324858000017 PM 23591291 ER PT J AU Shariff, N Desai, RV Patel, K Ahmed, MI Fonarow, GC Rich, MW Aban, IB Banach, M Love, TE White, M Aronow, WS Epstein, AE Ahmed, A AF Shariff, Nasir Desai, Ravi V. Patel, Kanan Ahmed, Mustafa I. Fonarow, Gregg C. Rich, Michael W. Aban, Inmaculada B. Banach, Maciej Love, Thomas E. White, Michel Aronow, Wilbert S. Epstein, Andrew E. Ahmed, Ali TI Rate-control versus Rhythm-control Strategies and Outcomes in Septuagenarians with Atrial Fibrillation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Atrial fibrillation; Hospitalization; Mortality; Propensity score; Older adults; Rate control; Rhythm control ID RENIN-ANGIOTENSIN INHIBITION; SYSTOLIC HEART-FAILURE; CHRONIC KIDNEY-DISEASE; MANAGEMENT AFFIRM; PROPENSITY SCORE; RANDOMIZED-TRIAL; COSTS; RISK AB BACKGROUND: The prevalence of atrial fibrillation substantially increases after 70 years of age. However, the effect of rate-control versus rhythm-control strategies on outcomes in these patients remains unclear. METHODS: In the randomized Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 4060 patients (mean age 70 years, range 49-80 years) with paroxysmal and persistent atrial fibrillation were randomized to rate-control versus rhythm-control strategies. Of these, 2248 were 70-80 years, of whom 1118 were in the rate-control group. Propensity scores for rate-control strategy were estimated for each of the 2248 patients and were used to assemble a cohort of 937 pairs of patients receiving rate-control versus rhythm-control strategies, balanced on 45 baseline characteristics. RESULTS: Matched patients had a mean age of 75 years; 45% were women, 7% were nonwhite, and 47% had prior hospitalizations due to arrhythmias. During 3.4 years of mean follow-up, all-cause mortality occurred in 18% and 23% of matched patients in the rate-control and rhythm-control groups, respectively (hazard ratio [HR] associated with rate control, 0.77; 95% confidence interval [CI], 0.63-0.94; P = .010). HRs (95% CIs) for cardiovascular and noncardiovascular mortality associated with rate control were 0.88 (0.65-1.18) and 0.62 (0.46-0.84), respectively. All-cause hospitalization occurred in 61% and 68% of rate-control and rhythm-control patients, respectively (HR 0.76; 95% CI, 0.68-0.86). HRs (95% CIs) for cardiovascular and noncardiovascular hospitalization were 0.66 (0.56-0.77) and 1.07 (0.91-1.27), respectively. CONCLUSION: In septuagenarian patients with atrial fibrillation, compared with rhythm-control, a rate-control strategy was associated with significantly lower mortality and hospitalization. (c) 2013 Elsevier Inc. All rights reserved. C1 [Shariff, Nasir] Univ Pittsburgh, Pittsburgh, PA USA. [Desai, Ravi V.] Lehigh Valley Hosp, Allentown, PA USA. [Patel, Kanan; Ahmed, Mustafa I.; Aban, Inmaculada B.; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Rich, Michael W.] Washington Univ, St Louis, MO USA. [Banach, Maciej] Med Univ Lodz, Lodz, Poland. [Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [White, Michel] Montreal Heart Inst, Quebec City, PQ, Canada. [Aronow, Wilbert S.] New York Med Coll, Valhalla, NY 10595 USA. [Epstein, Andrew E.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Epstein, Andrew E.] Univ Penn, Philadelphia, PA 19104 USA. [Ahmed, Ali] Vet Affairs Med Ctr, Birmingham, AL USA. RP Ahmed, A (reprint author), Univ Alabama Birmingham, 1720 2nd Ave South,CH-19,Suite 219, Birmingham, AL 35294 USA. EM aahmed@uab.edu RI Banach, Maciej/A-1271-2009 OI Banach, Maciej/0000-0001-6690-6874 FU National Institutes of Health from the National Heart, Lung, and Blood Institute [R01-HL085561, R01-HL085561-S, R01-HL097047] FX AA was, in part, supported by the National Institutes of Health through grants (R01-HL085561, R01-HL085561-S, and R01-HL097047) from the National Heart, Lung, and Blood Institute and a generous gift from Ms. Jean B. Morris of Birmingham, Alabama. NR 31 TC 10 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD OCT PY 2013 VL 126 IS 10 BP 887 EP 893 DI 10.1016/j.amjmed.2013.04.021 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 218YV UT WOS:000324469800024 PM 24054956 ER PT J AU Bossone, E Pyeritz, RE O'Gara, P Harris, KM Braverman, AC Pape, L Russo, MJ Hughes, GC Tsai, TT Montgomery, DG Nienaber, CA Isselbacher, EM Eagle, KA AF Bossone, Eduardo Pyeritz, Reed E. O'Gara, Patrick Harris, Kevin M. Braverman, Alan C. Pape, Linda Russo, Mark J. Hughes, G. Chad Tsai, Thomas T. Montgomery, Daniel G. Nienaber, Christoph A. Isselbacher, Eric M. Eagle, Kim A. CA Int Registry Acute Aortic TI Acute Aortic Dissection in Blacks: Insights from the International Registry of Acute Aortic Dissection SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aorta; Epidemiology; Mortality ID ACUTE MYOCARDIAL-INFARCTION; OUTCOMES; SURVIVAL; IRAD AB BACKGROUND: Few data exist on race-related differences in acute aortic dissection patients. METHODS: We evaluated black (n = 189, 14%) or white (n = 1165, 86%) patients (mean age 62.8 +/- 15.3 years; 36.4% women) enrolled in 13 US centers participating in the International Registry of Acute Aortic Dissection. We excluded patients of other racial descent. RESULTS: Type B acute aortic dissection was more frequent in the black cohort (52.4% vs 39.3%, P = .001). Black patients were younger (mean age 54.6 +/- 12.8 years vs 64.2 +/- 15.2 years, P <.001) and more likely to have a history of cocaine abuse (12% vs 1.6%, P <.001), hypertension (89.7% vs 73.9%, P <.001), and diabetes (13.2% vs 6.4%, P = .001). Conversely, they were less likely to have bicuspid aortic valve (1.8% vs 5.8%, P = .029), iatrogenic dissection (0.5% vs 4.5%, P = .010), and prior aortic dissection repair (7.7% vs 12.8%, P = .047). Presenting features were similar except for more abdominal pain (44.6% vs 30.6%, P <.001) and left ventricular hypertrophy on echocardiogram (44.2% vs 20.1%, P <.001) in blacks. Management was similar. Hypotension/shock/tamponade was less common (7.6% vs 20.1%, P <.001), whereas acute kidney failure was more common (41.0% vs 21.7%, P <.001) in blacks. Mortality was similar in-hospital (14.3% vs 19.1%, P = .110, odds ratio 0.704, 95% confidence interval 0.457-1.085) and at 3 years postdischarge, as evaluated by Kaplan-Meier survival analysis (22.0% vs 14.3%, P = .224, SE = 0.062 and 0.018). CONCLUSIONS: Our study shows differences in type, etiology, and presentation of blacks and whites with acute aortic dissection, yet similar mortality for these cohorts. (c) 2013 Elsevier Inc. All rights reserved. C1 [Bossone, Eduardo] Univ Hosp, Heart Dept, Salerno, Italy. [Pyeritz, Reed E.] Univ Penn, Philadelphia, PA 19104 USA. [O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harris, Kevin M.] Minneapolis Heart Inst, Minneapolis, MN USA. [Braverman, Alan C.] Washington Univ, St Louis, MO USA. [Pape, Linda] Univ Massachusetts, Worcester, MA 01605 USA. [Russo, Mark J.] Univ Chicago, Chicago, IL 60637 USA. [Hughes, G. Chad] Duke Univ, Durham, NC USA. [Tsai, Thomas T.] Univ Colorado, Aurora, CO USA. [Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nienaber, Christoph A.] Univ Hosp Eppendorf Rostock, Rostock, Germany. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bossone, E (reprint author), Univ Salerno, Div Cardiol, Via Pr Amedeo 36, I-83023 Lauro, AV, Italy. EM ebossone@hotmail.com FU W.L. Gore & Associates, Inc.; Varbedian Aortic Research Fund; Hewlett Foundation; Mardigian Foundation; UM Faculty Group Practice; Terumo FX W.L. Gore & Associates, Inc., Varbedian Aortic Research Fund, Hewlett Foundation, Mardigian Foundation, UM Faculty Group Practice, Terumo. NR 15 TC 12 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2013 VL 126 IS 10 BP 909 EP 915 DI 10.1016/j.amjmed.2013.04.020 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 218YV UT WOS:000324469800027 PM 23953874 ER PT J AU Mammoto, T Jiang, A Jiang, E Panigrahy, D Kieran, MW Mammoto, A AF Mammoto, Tadanori Jiang, Amanda Jiang, Elisabeth Panigrahy, Dipak Kieran, Mark W. Mammoto, Akiko TI Role of Collagen Matrix in Tumor Angiogenesis and Glioblastoma Multiforme Progression SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; PRIMARY BRAIN-TUMORS; LYSYL OXIDASE; EXTRACELLULAR-MATRIX; CANCER-CELLS; INVASIVE PHENOTYPE; MALIGNANT GLIOMA; WILSONS-DISEASE; THERAPY; COPPER AB Glioblastoma is a highly vascularized brain tumor, and antiangiogenic therapy improves its progression-free survival. However, current antiangiogenic therapy induces serious adverse effects including neuronal cytotoxicity and tumor invasiveness and resistance to therapy. Although it has been suggested that the physical microenvironment has a key role in tumor angiogenesis and progression, the mechanism by which physical properties of extracellular matrix control tumor angiogenesis and glioblastoma progression is not completely understood. Herein we show that physical compaction (the process in which cells gather and pack together and cause associated changes in cell shape and size) of human glioblastoma cell lines U87MG, U251, and LN229 induces expression of collagen types IV and VI and the collagen crosslinking enzyme lysyl oxidase and up-regulates in vitro expression of the angiogenic factor vascular endothelial growth factor. The lysyl oxidase inhibitor beta-aminopropionitrile disrupts collagen structure in the tumor and inhibits tumor angiogenesis and glioblastoma multiforme growth in a mouse orthotopic brain tumor model. Similarly, D-penicillamine, which inhibits Lysyl oxidase enzymatic activity by depleting intracerebral copper, also exhibits antiangiogenic effects on brain tumor growth in mice. These findings suggest that tumor microenvironment controlled by collagen structure is important in tumor angiogenesis and brain tumor progression. C1 [Mammoto, Tadanori; Jiang, Amanda; Jiang, Elisabeth; Panigrahy, Dipak; Kieran, Mark W.; Mammoto, Akiko] Boston Childrens Hosp, Vasc Biol Program, Dept Surg, Boston, MA 02115 USA. [Mammoto, Tadanori; Jiang, Amanda; Jiang, Elisabeth; Panigrahy, Dipak; Kieran, Mark W.; Mammoto, Akiko] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Panigrahy, Dipak; Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Mammoto, A (reprint author), Boston Childrens Hosp, Vasc Biol Program, KFRL11005B,1 Blackfan Circle, Boston, MA 02115 USA. EM akiko.mammoto@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU American Heart Association; William Randolph Hearst Award; American Brain Tumor Association; Children's Hospital Boston Faculty Career Development Fellowship; Stop and Shop Pediatric Brain Tumor Fund; C.J. Buckley Pediatric Brain Tumor Fund; National Cancer Institute, NIH [R01 CA148633]; Department of Defense [W81XWH-05-1-0115] FX Supported by funds from the American Heart Association (A.M.), a William Randolph Hearst Award (A.M.), the American Brain Tumor Association (A.M.), a Children's Hospital Boston Faculty Career Development Fellowship (T.M.), the Stop and Shop Pediatric Brain Tumor Fund (M.W.K.), the C.J. Buckley Pediatric Brain Tumor Fund (M.W.K), grant R01 CA148633 from the National Cancer Institute, NIH (D.P.), and grant W81XWH-05-1-0115 from Department of Defense. NR 71 TC 26 Z9 26 U1 1 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2013 VL 183 IS 4 BP 1293 EP 1305 DI 10.1016/j.ajpath.2013.06.026 PG 13 WC Pathology SC Pathology GA 227MU UT WOS:000325118800024 PM 23928381 ER PT J AU Jin, JF Zhang, XM Lu, ZY Perry, DM Li, YC Russo, SB Cowart, LA Hannun, YA Huang, Y AF Jin, Junfei Zhang, Xiaoming Lu, Zhongyang Perry, David M. Li, Yanchun Russo, Sarah Brice Cowart, L. Ashley Hannun, Yusuf A. Huang, Yan TI Acid sphingomyelinase plays a key role in palmitic acid-amplified inflammatory signaling triggered by lipopolysaccharide at low concentrations in macrophages SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE fatty acid; sphingomyelinase; lipopolysaccharide; toll-like receptor; inflammation ID FATTY-ACIDS; INSULIN-RESISTANCE; HUMAN MONOCYTES; SPHINGOLIPID BIOSYNTHESIS; CERAMIDE SYNTHESIS; INTERLEUKIN-6; MECHANISMS; EXPRESSION; ENDOTOXIN; IL-6 AB Periodontal disease is more prevalent and severe in patients with diabetes than in nondiabetic patients. In addition to diabetes, a large number of studies have demonstrated an association between obesity and chronic periodontal disease. However, the underlying mechanisms have not been well understood. Since plasma free fatty acids (FAs) are elevated in obese patients and saturated FAs such as palmitic acid (PA) have been shown to increase host inflammatory response, we sought to find out how PA interacts with lipopolysaccharide (LPS), an important pathological factor involved in periodontal disease, to enhance inflammation. We found that whereas low concentration of LPS (1 ng/ml) stimulated interleukin (IL)-6 expression in RAW 264.7 macrophages, PA further augmented it fourfold. Besides IL-6, PA amplified the stimulatory effect of LPS on a large amount of Toll-like receptor (TLR) 4-mediated expression of proinflammatory signaling molecules such as IL-1 receptor-associated kinase-like 2 and proinflammatory molecules, including monocyte chemotactic protein-1 and colony-stimulating factor. We also observed that PA augmented TLR4 but not TLR2 signal, and the augmentation was mediated by nuclear factor-kappa B (NF-kappa B) pathways. To further elucidate the regulatory mechanism whereby PA amplifies LPS signal, our studies showed that PA and LPS synergistically increased hydrolysis of sphingomyelin by stimulating acid sphingomyelinase (ASMase) activity, which contributed to a marked increase in ceramide production and IL-6 upregulation. Taken together, this study has demonstrated that PA markedly augments TLR4-mediated proinflammatory signaling triggered by low concentration of LPS in macrophages, and ASMase plays a key role in the augmentation. C1 [Lu, Zhongyang; Cowart, L. Ashley; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Jin, Junfei; Zhang, Xiaoming; Li, Yanchun; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Perry, David M.; Russo, Sarah Brice; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Hannun, Yusuf A.] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; National Institutes of Health [DE-016353, CA-97132]; Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]; Lipidomics Core in the SC Lipidomics and Pathobiology COBRE [P20 RR017677]; National Center for Research Resources; Office of the Director of the National Institutes of Health [C06 RR-018823] FX This work was supported by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs and National Institutes of Health Grant DE-016353 (to Y. Huang) and Grant CA-97132 (to Y. A. Hannun). The work on sphingolipid analysis was supported in part by the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313), the Lipidomics Core in the SC Lipidomics and Pathobiology COBRE (P20 RR017677), and the National Center for Research Resources and the Office of the Director of the National Institutes of Health through Grant No. C06 RR-018823. NR 54 TC 17 Z9 17 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2013 VL 305 IS 7 BP E853 EP E867 DI 10.1152/ajpendo.00251.2013 PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 230MO UT WOS:000325344800010 PM 23921144 ER PT J AU Cardarella, S Johnson, BE AF Cardarella, Stephanie Johnson, Bruce E. TI The Impact of Genomic Changes on Treatment of Lung Cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung cancer; cancer genomics; molecular targeted therapy ID HARBORING BRAF MUTATIONS; EML4-ALK FUSION GENE; PHASE-II TRIAL; SOMATIC MUTATIONS; KINASE INHIBITOR; ALK INHIBITOR; ADENOCARCINOMA; RET; GEFITINIB; EGFR AB The remarkable success of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in patients with EGFR mutations and ALK rearrangements, respectively, introduced the era of targeted therapy in advanced non-small cell lung cancer (NSCLC), shifting treatment from platinum-based combination chemotherapy to molecularly tailored therapy. Recent genomic studies in lung adenocarcinoma identified other potential therapeutic targets, including ROS1 rearrangements, RET fusions, MET amplification, and activating mutations in BRAF, HER2, and KRAS in frequencies exceeding 1%. Lung cancers that harbor these genomic changes can potentially be targeted with agents approved for other indications or under clinical development. The need to generate increasing amounts of genomic information should prompt health-care providers to be mindful of the amounts of tissue needed for these assays when planning diagnostic procedures. In this review, we summarize oncogenic drivers in NSCLC that can be currently detected, highlight their potential therapeutic implications, and discuss practical considerations for successful application of tumor genotyping in clinical decision making. C1 [Cardarella, Stephanie; Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Cardarella, Stephanie; Johnson, Bruce E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cardarella, Stephanie; Johnson, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,Dana 1234, Boston, MA 02215 USA. EM bejohnson@partners.org FU Dana-Farber/Harvard Cancer Center Lung Cancer Specialized Program in Research Excellence (SPORE) [P50 CA090578]; American Society of Clinical Oncology (ASCO) Conquer Cancer Foundation Translational Research Professorship; National Institutes of Health [5R01-CA114465]; Alice and Stephen D. Cutler Investigator Fund in Thoracic Oncology at the Dana-Farber Cancer Institute FX Funded in part by the Dana-Farber/Harvard Cancer Center Lung Cancer Specialized Program in Research Excellence (SPORE) P50 CA090578; the American Society of Clinical Oncology (ASCO) Conquer Cancer Foundation Translational Research Professorship (B.E.J.); National Institutes of Health grant 5R01-CA114465 (B.E.J.); and the Alice and Stephen D. Cutler Investigator Fund in Thoracic Oncology at the Dana-Farber Cancer Institute (S.C.). NR 50 TC 40 Z9 40 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2013 VL 188 IS 7 BP 770 EP 775 DI 10.1164/rccm.201305-0843PP PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230OG UT WOS:000325350600006 PM 23841470 ER PT J AU Gabler, NB Ratcliffe, SJ Wagner, J Asch, DA Rubenfeld, GD Angus, DC Halpern, SD AF Gabler, Nicole B. Ratcliffe, Sarah J. Wagner, Jason Asch, David A. Rubenfeld, Gordon D. Angus, Derek C. Halpern, Scott D. TI Mortality among Patients Admitted to Strained Intensive Care Units SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE critical care; resource allocation; intensive care unit; physician staffing; regionalization ID CRITICALLY-ILL PATIENTS; OUTCOMES; STATES; WORKLOAD; REGIONALIZATION; POPULATION; ALLOCATION; OCCUPANCY; SHORTAGE; CRISIS AB Rationale: The aging population may strain intensive care unit (ICU) capacity and adversely affect patient outcomes. Existing fluctuations in demand for ICU care offer an opportunity to explore such relationships. Objectives: To determine whether transient increases in ICU strain influence patient mortality, and to identify characteristics of ICUs that are resilient to surges in capacity strain. Methods: Retrospective cohort study of 264,401 patients admitted to 155 U. S. ICUs from 2001 to 2008. We used logistic regression to examine relationships of measures of ICU strain (census, average acuity, and proportion of new admissions) near the time of ICU admission with mortality. Measurements and Main Results: A total of 36,465 (14%) patients died in the hospital. ICU census on the day of a patient's admission was associated with increased mortality (odds ratio [OR], 1.02 per standardized unit increase; 95% confidence interval [CI]: 1.00, 1.03). This effect was greater among ICUs employing closed (OR, 1.07; 95% CI: 1.02, 1.12) versus open (OR, 1.01; 95% CI: 0.99, 1.03) physician staffing models (interaction P value = 0.02). The relationship between census and mortality was stronger when the census was composed of higher acuity patients (interaction P value < 0.01). Averaging strain over the first 3 days of patients' ICU stays yielded similar results except that the proportion of new admissions was now also associated with mortality (OR, 1.04 for each 10% increase; 95% CI: 1.02, 1.06). Conclusions: Several sources of ICU strain are associated with small but potentially important increases in patient mortality, particularly in ICUs employing closed staffing models. Although closed ICUs may promote favorable outcomes under static conditions, they are susceptible to being overwhelmed by patient influxes. C1 [Gabler, Nicole B.; Ratcliffe, Sarah J.; Halpern, Scott D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gabler, Nicole B.; Wagner, Jason; Angus, Derek C.; Halpern, Scott D.] Univ Penn, Fostering Improvement End of Life Decis Sci FIELD, Philadelphia, PA 19104 USA. [Wagner, Jason; Halpern, Scott D.] Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Asch, David A.; Halpern, Scott D.] Univ Penn, Ctr Innovat, Philadelphia, PA 19104 USA. [Asch, David A.; Halpern, Scott D.] Univ Penn, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Halpern, Scott D.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Asch, David A.] VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Rubenfeld, Gordon D.] Sunnybrook Hlth Sci Ctr, Program Trauma Crit Care & Emergency Med, Toronto, ON M4N 3M5, Canada. [Angus, Derek C.] Univ Pittsburgh, Sch Med, Dept Crit Care, Pittsburgh, PA USA. RP Halpern, SD (reprint author), Univ Penn, Perelman Sch Med, 719 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM shalpern@exchange.upenn.edu OI Asch, David/0000-0002-7970-286X; Ratcliffe, Sarah/0000-0002-6644-8284 FU Agency for Healthcare Research and Quality [K08HS018406]; Society of Critical Care Medicine Vision Grant FX Supported by K08HS018406 from the Agency for Healthcare Research and Quality and a Society of Critical Care Medicine Vision Grant (S.D.H.). NR 37 TC 27 Z9 28 U1 0 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2013 VL 188 IS 7 BP 800 EP 806 DI 10.1164/rccm.201304-0622OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230OG UT WOS:000325350600010 PM 23992449 ER PT J AU Tirumani, SH Jagannathan, JP Krajewski, KM Shinagare, AB Jacene, H Ramaiya, NH AF Tirumani, Sree Harsha Jagannathan, Jyothi P. Krajewski, Katherine M. Shinagare, Atul B. Jacene, Heather Ramaiya, Nikhil H. TI Imatinib and Beyond in Gastrointestinal Stromal Tumors: A Radiologist's Perspective SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT; gastrointestinal stromal tumor; imatinib; PET/CT ID POSITRON-EMISSION-TOMOGRAPHY; MOLECULAR TARGETED THERAPY; RENAL-CELL CARCINOMA; PHASE-II TRIAL; RESPONSE ASSESSMENT; FDG-PET; MESYLATE; CRITERIA; GIST; CT AB OBJECTIVE. The purpose of this article is to review the decade-long experience with imatinib and other molecular targeted agents in the treatment of gastrointestinal stromal tumor (GIST). CONCLUSION. Tremendous progress has been made in the medical management of GIST since the inception of imatinib, and imaging has played a key role in understanding the typical and atypical responses of GIST to molecular targeted therapies. C1 [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Jacene, Heather; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02114 USA. [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Shinagare, Atul B.; Jacene, Heather; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02114 USA. EM stirumani@partners.org NR 44 TC 12 Z9 12 U1 0 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2013 VL 201 IS 4 BP 801 EP 810 DI 10.2214/AJR.12.10003 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 224FL UT WOS:000324868000037 PM 24059369 ER PT J AU Kim, KW Krajewski, KM Nishino, M Jagannathan, JP Shinagare, AB Tirumani, SH Ramaiya, NH AF Kim, Kyung Won Krajewski, Katherine M. Nishino, Mizuki Jagannathan, Jyothi P. Shinagare, Atul B. Tirumani, Sree Harsha Ramaiya, Nikhil H. TI Update on the Management of Gastroenteropancreatic Neuroendocrine Tumors With Emphasis on the Role of Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE gastroenteropancreatic neuroendocrine tumor; guidelines; molecular targeted therapy ID CLINICAL-PRACTICE GUIDELINES; RESPONSE CRITERIA; CARCINOID-TUMORS; TARGETED THERAPY; CELL CARCINOMA; SOMATOSTATIN; METASTASIS; NEOPLASMS; DIAGNOSIS; RECIST AB OBJECTIVE. The purposes of this article are to review the current management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) based on the 2012 National Comprehensive Cancer Network guidelines and to describe the role of imaging in a multidisciplinary approach. CONCLUSION. The management of GEP-NETs has become complex, requiring a multidisciplinary approach. The World Health Organization classification of GEP-NETs has been revised; the U.S. Food and Drug Administration has approved molecular targeted agents (sunitinib, everolimus) for the treatment of pancreatic NETs; and the National Comprehensive Cancer Network clinical practice guidelines have been updated. C1 [Kim, Kyung Won; Krajewski, Katherine M.; Nishino, Mizuki; Jagannathan, Jyothi P.; Shinagare, Atul B.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea. [Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul, South Korea. RP Kim, KW (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02115 USA. EM medimash@gmail.com FU (NCI) from the National Institutes of Health [1K23CA157631] FX M. Nishino supported by 1K23CA157631 (NCI) from the National Institutes of Health. NR 36 TC 7 Z9 7 U1 0 U2 11 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2013 VL 201 IS 4 BP 811 EP 824 DI 10.2214/AJR.12.10240 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 224FL UT WOS:000324868000038 PM 24059370 ER PT J AU Gunn, AJ Alabre, CI Bennett, SE Kautzky, M Krakower, T Palamara, K Choy, G AF Gunn, Andrew J. Alabre, Claude I. Bennett, Susan E. Kautzky, Mira Krakower, Thalia Palamara, Kerri Choy, Garry TI Structured Feedback From Referring Physicians: A Novel Approach to Quality Improvement in Radiology Reporting SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE peer review; quality improvement; radiology reporting ID STYLE AB OBJECTIVE. There is considerable interest in improving radiology reporting practices through peer review, and the inclusion of structured feedback from referring physicians may improve this process. The purpose of this article is to evaluate the feasibility of this type of novel peer-review system. MATERIALS AND METHODS. Five referring physicians from our institution participated as reviewers. Reports from abdominal CT, chest CT, brain MRI, and abdominal ultrasound were eligible for review if the indication was "abdominal pain," "shortness of breath," "headache," and "pain," respectively. Reports were excluded if the examinations were normal or ordered as follow-up. Forty-eight reports (12 from each group) were then selected at random and distributed to the referring physicians along with the clinical scenario and an evaluation form for each examination. RESULTS. The reports were found to be clinically useful (average, 3.8 on a 1-5 scale), allowing for good confidence in clinical decision making (average, 3.7). The most common problems were unclear language, typographical errors, and reports that did not answer the clinical question. Of the reports, 35.4% contained recommendations for further diagnosis or treatment, and 84.7% of these recommendations were deemed clinically appropriate. The participating physicians thought that the results of 31.2% of the examinations should have been directly communicated to the ordering provider. CONCLUSION. Radiology reports and recommendations were clinically useful, even though problems with language, typographical errors, answering the clinical question, and direct communication of examination results were identified. Structured feedback from referring physicians is a novel approach to the peer-review process that may identify problems that go unnoticed by the radiologist, thereby improving reporting practices. C1 [Gunn, Andrew J.; Choy, Garry] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Alabre, Claude I.; Bennett, Susan E.; Kautzky, Mira; Krakower, Thalia; Palamara, Kerri] Harvard Univ, Massachusetts Gen Hosp, Dept Internal Med, Sch Med, Boston, MA 02114 USA. [Choy, Garry] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med,Div Emergency Radiol & Teleradiol, Boston, MA 02114 USA. RP Gunn, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, FND 216,55 Fruit St, Boston, MA 02114 USA. EM agunn@partners.org NR 26 TC 8 Z9 8 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2013 VL 201 IS 4 BP 853 EP 857 DI 10.2214/AJR.12.10450 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 224FL UT WOS:000324868000043 PM 24059375 ER PT J AU Wu, CC Khorashadi, L Abbott, GF Gilman, MD AF Wu, Carol C. Khorashadi, Leila Abbott, Gerald F. Gilman, Matthew D. TI Common Blind Spots on Chest CT: Where Are They All Hiding? Part 1-Airways, Lungs, and Pleura SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE chest CT; lung cancer screening ID PULMONARY NODULES; IMAGING FINDINGS; CANCER; CARCINOMA; IMAGES C1 [Wu, Carol C.; Abbott, Gerald F.; Gilman, Matthew D.] Massachusetts Gen Hosp, Dept Radiol Thorac Imaging & Intervent, Boston, MA 02114 USA. [Khorashadi, Leila] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02238 USA. RP Wu, CC (reprint author), Massachusetts Gen Hosp, Dept Radiol Thorac Imaging & Intervent, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM cwu8@partners.org NR 11 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2013 VL 201 IS 4 BP W533 EP W538 DI 10.2214/AJR.12.9354 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 224FL UT WOS:000324868000002 PM 24059389 ER PT J AU Permaul, P Sheehan, WJ Baxi, SN Gaffin, JM Fu, CX Petty, CR Gold, DR Phipatanakul, W AF Permaul, Perdita Sheehan, William J. Baxi, Sachin N. Gaffin, Jonathan M. Fu, Chunxia Petty, Carter R. Gold, Diane R. Phipatanakul, Wanda TI Predictors of indoor exposure to mouse allergen in inner-city elementary schools SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID ASTHMA; HOMES; CHILDREN; DESIGN; URBAN C1 [Permaul, Perdita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Permaul, Perdita; Sheehan, William J.; Baxi, Sachin N.; Gaffin, Jonathan M.; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Sheehan, William J.; Baxi, Sachin N.; Gaffin, Jonathan M.; Petty, Carter R.; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Fu, Chunxia; Gold, Diane R.; Phipatanakul, Wanda] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Permaul, P (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM wanda.phipatanakul@childrens.harvard.edu FU NCRR NIH HHS [UL1 RR025758]; NHLBI NIH HHS [U10 HL098102, U10HL098102]; NIAID NIH HHS [K23 AI106945, R01 AI073964, R01AI 073964, K24 AI106822, K23AI106945, R01 AI 073964-02S1, K24 AI 106822] NR 10 TC 6 Z9 6 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD OCT PY 2013 VL 111 IS 4 BP 299 EP 301 DI 10.1016/j.anai.2013.07.028 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 223QG UT WOS:000324821300014 PM 24054369 ER PT J AU Blashill, AJ Mayer, KH Crane, H Magidson, JF Grasso, C Mathews, WC Saag, MS Safren, SA AF Blashill, Aaron J. Mayer, Kenneth H. Crane, Heidi Magidson, Jessica F. Grasso, Chris Mathews, W. Christopher Saag, Michael S. Safren, Steven A. TI Physical Activity and Health Outcomes Among HIV-Infected Men Who Have Sex with Men: A Longitudinal Mediational Analysis SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE HIV/AIDS; Physical activity; Depression; Adherence; Viral load ID BEHAVIORAL ACTIVATION TREATMENT; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; INJECTION-DRUG USERS; DEPRESSION CBT-AD; ANTIRETROVIRAL THERAPY; PSYCHOSOCIAL FACTORS; DISEASE PROGRESSION; SEROPOSITIVE WOMEN; STRESS-MANAGEMENT AB Low physical activity is associated with depression, which may, in turn, negatively impact antiretroviral therapy (ART) adherence among HIV-infected individuals; however, prior studies have not investigated the relationships between physical inactivity and ART non-adherence. The purpose of this study was to examine the association of physical inactivity, depression, ART non-adherence, and viral load in HIV-infected men who have sex with men. The sample (N = 860) was from a large, multicenter cohort of HIV-infected patients engaged in clinical care. Across time, depression mediated the relationship between physical inactivity and ART non-adherence (gamma = 0.075) and the relationship between physical inactivity and viral load (gamma = 0.05). ART non-adherence mediated the relationship between depression and viral load (gamma = 0.002) and the relationship between physical inactivity and viral load (gamma = 0.009). Low levels of physical activity predicted increased depression and poor ART adherence over time, which subsequently predicted higher viral load. C1 [Blashill, Aaron J.; Magidson, Jessica F.; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blashill, Aaron J.; Mayer, Kenneth H.; Magidson, Jessica F.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Blashill, Aaron J.; Mayer, Kenneth H.; Grasso, Chris; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Crane, Heidi] Univ Washington, Seattle, WA 98195 USA. [Mathews, W. Christopher] Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. [Saag, Michael S.] Univ Alabama Birmingham, Birmingham, AL USA. RP Blashill, AJ (reprint author), 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org RI Mathews, William/E-4451-2010 OI Mathews, William/0000-0002-2352-0725 FU NIAID NIH HHS [5P30AI060354-08, P30 AI060354, R24 AI067039, R24AI067039]; NIMH NIH HHS [T32 MH093310, K23 MH096647, K23MH096647, K24 MH094214, R01 MH084759, R01MH084759] NR 69 TC 2 Z9 2 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2013 VL 46 IS 2 BP 149 EP 156 DI 10.1007/s12160-013-9489-3 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 219GI UT WOS:000324493900006 PM 23483379 ER PT J AU Blashill, AJ Traeger, L AF Blashill, Aaron J. Traeger, Lara TI Indoor Tanning Use Among Adolescent Males: The Role of Perceived Weight and Bullying SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID APPEARANCE-FOCUSED INTERVENTION; PREVENT SKIN-CANCER; UNITED-STATES; BODY DISSATISFACTION; BEHAVIORS; YOUTH; BOYS; MUSCULARITY; EFFICACY; MODEL C1 [Blashill, Aaron J.; Traeger, Lara] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Blashill, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NIMH NIH HHS [K23MH096647, K23 MH096647] NR 30 TC 5 Z9 5 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2013 VL 46 IS 2 BP 232 EP 236 DI 10.1007/s12160-013-9491-9 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 219GI UT WOS:000324493900014 PM 23494291 ER PT J AU Kovach, AE Cheng, GZ Channick, CL Channick, RN Muniappan, A Gaissert, HA Kradin, RL AF Kovach, Alexandra E. Cheng, George Z. Channick, Colleen L. Channick, Richard N. Muniappan, Ashok Gaissert, Henning A. Kradin, Richard L. TI Postradiofrequency ablation inflammatory pseudotumor associated with pulmonary venoocclusive disease: case report and review of the literature SO ANNALS OF DIAGNOSTIC PATHOLOGY LA English DT Article DE Pulmonary vein stenosis; Veno-occlusive disease; Radiofrequency ablation; Inflammatory pseudotumor ID RADIOFREQUENCY CATHETER ABLATION; CHRONIC ATRIAL-FIBRILLATION; VEIN STENOSIS; OCCLUSION; LESIONS AB Radiofrequency ablation of pulmonary veins is a common therapeutic intervention for atrial fibrillation. Pulmonary vein stenosis and venoocclusive disease are recognized complications, but the spectrum of pathologies postablation have not been previously reviewed. A recent case at our hospital showed a left hilar soft tissue mass in association with superior pulmonary vein stenosis in a patient 4 years postablation. On resection, this proved to be an inflammatory pseudotumor composed of myofibroblasts in an organizing pneumonia-type pattern with adjacent dendriform ossifications. Pulmonary venoocclusive change was a prominent feature. Literature on the histopathology of postradiofrequency ablation complications is limited. The severity of vascular pathology appears to increase with the postablation interval. Although pulmonary vascular changes are the most common late finding, fibroinflammatory changes including pulmonary pseudotumor formation, attributable to thermal injury, should be considered in the differential diagnosis of these cases. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kovach, Alexandra E.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cheng, George Z.; Channick, Colleen L.; Channick, Richard N.; Kradin, Richard L.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Muniappan, Ashok; Gaissert, Henning A.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM rkradin@partners.org NR 15 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1092-9134 J9 ANN DIAGN PATHOL JI Ann. Diagn. Pathol. PD OCT PY 2013 VL 17 IS 5 BP 466 EP 469 DI 10.1016/j.anndiagpath.2012.11.002 PG 4 WC Pathology SC Pathology GA 224NW UT WOS:000324896100015 PM 23352326 ER PT J AU Zadra, G Photopoulos, C Loda, M AF Zadra, Giorgia Photopoulos, Cornelia Loda, Massimo TI The fat side of prostate cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Prostate cancer; Lipid metabolism; Fatty acids; Imaging; Metabolic diseases ID ACTIVATED PROTEIN-KINASE; ATP-CITRATE LYASE; ACID SYNTHASE EXPRESSION; STEAROYL-COA DESATURASE; POSITRON-EMISSION-TOMOGRAPHY; AUTOCHTHONOUS MOUSE MODEL; TUMOR-CELL METABOLISM; DE-NOVO LIPOGENESIS; CHOLINE KINASE; BREAST-CANCER AB Prostate cancer (PCa) metabolism appears to be unique in comparison with other types of solid cancers. Normal prostate cells mainly rely on glucose oxidation to provide precursors for the synthesis and secretion of citrate, resulting in an incomplete Krebs cycle and minimal oxidative phosphorylation for energy production. In contrast, during transformation, PCa cells no longer secrete citrate and they reactivate the Krebs cycle as energy source. Moreover, primary PCas do not show increased aerobic glycolysis and therefore they are not efficiently detectable with F-18-FDG-PET. However, increased de nova lipid synthesis, strictly intertwined with deregulation in classical oncogenes and oncosuppressors, is an early event of the disease. Up-regulation and increased activity of lipogenic enzymes (including fatty add synthase and choline kinase) occurs throughout PCa carcinogenesis and correlates with worse prognosis and poor survival. Thus, lipid precursors such as acetate and choline have been successfully used as alternative tracers for PET imaging. Lipid synthesis intermediates and FA catabolism also emerged as important players in PCa maintenance. Finally, epidemiologic studies suggested that systemic metabolic disorders including obesity, metabolic syndrome, and diabetes as well as hypercaloric and fat-rich diets might increase the risk of PCa. However, how metabolic disorders contribute to PCa development and whether dietary lipids and de novo lipids synthesized intra-tumor are differentially metabolized still remains unclear. In this review, we examine the switch in lipid metabolism supporting the development and progression of PCa and we discuss how we can exploit its lipogenic nature for therapeutic and diagnostic purposes. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. (C) 2013 Elsevier B.V. All rights reserved. C1 [Zadra, Giorgia; Photopoulos, Cornelia; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London, England. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Longwood Ave,D1536, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU NIH [RO1CA131945]; American Italian Cancer Foundation; Andrea e Libi Lorini Foundation FX Prostate Cancer Foundation, the DF/HCC SPORE in Prostate Cancer (NIH/NCI P50 CA90381), and NIH grant RO1CA131945 to ML. GZ was supported by fellowships from the American Italian Cancer Foundation and from the Andrea e Libi Lorini Foundation. NR 211 TC 59 Z9 60 U1 3 U2 43 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD OCT PY 2013 VL 1831 IS 10 SI SI BP 1518 EP 1532 DI 10.1016/j.bbalip.2013.03.010 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 222GR UT WOS:000324719700004 PM 23562839 ER PT J AU Puterman, E Epel, ES Lin, J Blackburn, EH Gross, JJ Whooley, MA Cohen, BE AF Puterman, Eli Epel, Elissa S. Lin, Jue Blackburn, Elizabeth H. Gross, James J. Whooley, Mary A. Cohen, Beth E. TI Multisystem resiliency moderates the major depression-Telomere length association: Findings from the Heart and Soul Study SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Major depressive disorder; Telomeres; Cell aging; Resiliency; Social connections; Emotion regulation; Physical activity ID ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY; SOCIAL SUPPORT; EMOTION REGULATION; OLDER-ADULTS; CARDIOVASCULAR MORTALITY; DISPOSITIONAL OPTIMISM; INDIVIDUAL-DIFFERENCES; POSTMENOPAUSAL WOMEN; OXIDATIVE STRESS AB Major depressive disorder (MDD) has been associated with reduced leukocyte telomere length (LTL). It is not known, however, whether psychosocial and behavioral protective factors moderate this association. In the current study, we examine whether multisystem resiliency - defined by healthy emotion regulation, strong social connections, and health behaviors (sleep and exercise) - predicts LTL and mitigates previously demonstrated associations between depression diagnosis and LTL. LTL was measured, using a quantitative PCR assay, in 954 patients with stable cardiovascular disease in the Heart and Soul Study. In a fully adjusted model, high multisystem resiliency predicted longer LTL (b = 80.00, SE = 27.17, p = .003), whereas each individual factor did not. Multisystem resiliency significantly moderated the MDD-LTL association (p = .02). Specifically, MDD was significantly related to LTL at 1 SD below the mean of multisystem resiliency (b = -142.86, SE = 56.46, p = .01), but not at I SD above the mean (b = 49.07, SE = 74.51, p = .51). This study suggests that MDD associations with biological outcomes should be examined within a psychosocial-behavioral context, because this context shapes the nature of the direct relationship. Further research should explore the cognitive, neural, and other physiological pathways through which multisystem resiliency may confer biological benefit. (c) 2013 Elsevier Inc. All rights reserved. C1 [Puterman, Eli; Epel, Elissa S.; Lin, Jue; Blackburn, Elizabeth H.; Whooley, Mary A.; Cohen, Beth E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gross, James J.] Stanford Univ, Stanford, CA 94305 USA. [Whooley, Mary A.; Cohen, Beth E.] San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. RP Puterman, E (reprint author), Univ Calif San Francisco, 3333 Calif St Suite 465, San Francisco, CA 94143 USA. EM eli.puterman@ucsf.edu OI Puterman, Eli/0000-0002-5898-2348 FU NIH/NHLBI Grant [K99HL109247, K23 HL 094765-01]; Robert Wood Johnson Foundation; Irene Perstein Foundation; Department of Veterans Affairs, Washington, DC; National Heart Lung and Blood Institute, Bethesda, MD [R01 HL079235]; American Federation for Aging Research (Paul Beeson Scholars Program), New York, NY; Robert Wood Johnson Foundation (Faculty Scholars Program), Princeton, NJ; Ischemia Research and Education Foundation, South San Francisco, CA; Nancy Kirwan Heart Research Fund, San Francisco, CA FX We thank the study participants for their support and generous contribution of time. This research was supported in part by NIH/NHLBI Grant K99HL109247 and the Robert Wood Johnson Foundation to Dr. Puterman and NIH/NHLBI Grant K23 HL 094765-01 and a Grant from the Irene Perstein Foundation to Dr. Cohen. The Heart and Soul Study was funded by the Department of Veterans Affairs, Washington, DC, the National Heart Lung and Blood Institute (R01 HL079235), Bethesda, MD, the American Federation for Aging Research (Paul Beeson Scholars Program), New York, NY, the Robert Wood Johnson Foundation (Faculty Scholars Program), Princeton, NJ, the Ischemia Research and Education Foundation, South San Francisco, CA, and the Nancy Kirwan Heart Research Fund, San Francisco, CA. This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Medical Center, San Francisco, CA. The funding organizations had no role in the design or conduct of the study; data collection, management, analysis or interpretation of the data; or preparation, review or approval of the manuscript. NR 110 TC 18 Z9 19 U1 2 U2 32 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD OCT PY 2013 VL 33 BP 65 EP 73 DI 10.1016/j.bbi.2013.05.008 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 223EU UT WOS:000324788300010 PM 23727245 ER PT J AU Ganz, PA Yip, CH Gralow, JR Distelhorst, SR Albain, KS Andersen, BL Bevilacqua, JLB de Azambuja, E El Saghir, NS Kaur, R McTiernan, A Partridge, AH Rowland, JH Singh-Carlson, S Vargo, MM Thompson, B Anderson, BO AF Ganz, Patricia A. Yip, Cheng Har Gralow, Julie R. Distelhorst, Sandra R. Albain, Kathy S. Andersen, Barbara L. Bevilacqua, Jose Luiz B. de Azambuja, Evandro El Saghir, Nagi S. Kaur, Ranjit McTiernan, Anne Partridge, Ann H. Rowland, Julia H. Singh-Carlson, Savitri Vargo, Mary M. Thompson, Beti Anderson, Benjamin O. TI Supportive care after curative treatment for breast cancer (survivorship care): Resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement SO BREAST LA English DT Review DE Breast cancer; Supportive care; Survivorship; Low- and middle-income countries; Resource allocations ID QUALITY-OF-LIFE; FOLLOW-UP CARE; BODY-IMAGE; GUIDELINE IMPLEMENTATION; CULTURAL COMPETENCE; SEXUAL DYSFUNCTION; MEDICAL-EDUCATION; AMERICAN-SOCIETY; CONTROLLED-TRIAL; ARM LYMPHEDEMA AB Breast cancer survivors may experience long-term treatment complications, must live with the risk of cancer recurrence, and often experience psychosocial complications that require supportive care services. In low- and middle-income settings, supportive care services are frequently limited, and program development for survivorship care and long-term follow-up has not been well addressed. As part of the 5th Breast Health Global Initiative (BHGI) Global Summit, an expert panel identified nine key resources recommended for appropriate survivorship care, and developed resource-stratified recommendations to illustrate how health systems can provide supportive care services for breast cancer survivors after curative treatment, using available resources. Key recommendations include health professional education that focuses on the management of physical and psychosocial long-term treatment complications. Patient education can help survivors transition from a provider-intense cancer treatment program to a post-treatment provider partnership and self-management program, and should include: education on recognizing disease recurrence or metastases; management of treatment-related sequelae, and psychosocial complications; and the importance of maintaining a healthy lifestyle. Increasing community awareness of survivorship issues was also identified as an important part of supportive care programs. Other recommendations include screening and management of psychosocial distress; management of long-term treatment-related complications including lymphedema, fatigue, insomnia, pain, and women's health issues; and monitoring survivors for recurrences or development of second primary malignancies. Where possible, breast cancer survivors should implement healthy lifestyle modifications, including physical activity, and maintain a healthy weight. Health professionals should provide well-documented patient care records that can follow a patient as they transition from active treatment to follow-up care. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Yip, Cheng Har] Univ Malaya, Med Ctr, Kuala Lumpur, Malaysia. [Gralow, Julie R.; Anderson, Benjamin O.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Gralow, Julie R.; Distelhorst, Sandra R.; McTiernan, Anne; Thompson, Beti; Anderson, Benjamin O.] Fred Hutchinson Canc Ctr, Seattle, WA USA. [Albain, Kathy S.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Andersen, Barbara L.] Ohio State Univ, Columbus, OH 43210 USA. [Bevilacqua, Jose Luiz B.] Hosp Sirio Libanes, Sao Paulo, Brazil. [de Azambuja, Evandro] Inst Jules Bordet, B-1000 Brussels, Belgium. [El Saghir, Nagi S.] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. [Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rowland, Julia H.] NCI, Bethesda, MD 20892 USA. [Singh-Carlson, Savitri] Calif State Univ Long Beach, Sch Nursing, Long Beach, CA 90840 USA. [Vargo, Mary M.] Case Western Reserve Univ, MetroHlth Rehabil Inst Ohio, Cleveland, OH 44106 USA. RP Anderson, BO (reprint author), Univ Washington, Dept Surg, 1959 NE Pacific St,BB437A Bx 356410, Seattle, WA 98195 USA. EM banderso@fhcrc.org RI Yip, Cheng-Har/B-1909-2010; Bevilacqua, Jose Luiz/J-7739-2012 FU Fred Hutchinson Cancer Research Center; Susan G Komen for the Cure(R) [INT-3063.0/Tracking, 221664]; International Atomic Energy Agency Programme of Action for Cancer Therapy; National Cancer Institute; Lancet Oncology; Elsevier; American Society of Clinical Oncology; Sheikh Mohammed Hussein Al-Amoudi Center of Excellence in Breast Cancer; Pan American Health Organization; European Society of Medical Oncology; European School of Oncology; Open Society Foundations; LIVE-STRONG; Sanofi FX BHGI received (2012 Global Summit) grants and contributions from Fred Hutchinson Cancer Research Center, Susan G Komen for the Cure (R) (Contract ID: INT-3063.0/Tracking No: 221664), International Atomic Energy Agency Programme of Action for Cancer Therapy, National Cancer Institute, The Lancet Oncology, Elsevier, American Society of Clinical Oncology, Sheikh Mohammed Hussein Al-Amoudi Center of Excellence in Breast Cancer, Pan American Health Organization, European Society of Medical Oncology, European School of Oncology, Open Society Foundations, LIVE-STRONG, and an unrestricted educational grant from Sanofi. NR 115 TC 25 Z9 26 U1 2 U2 39 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2013 VL 22 IS 5 BP 606 EP 615 DI 10.1016/j.breast.2013.07.049 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 219OO UT WOS:000324516800006 PM 24007941 ER PT J AU Park, ER Traeger, L Willett, J Gerade, B Webster, A Rastegar, S Denninger, JW Lee, JM AF Park, Elyse R. Traeger, Lara Willett, Jessica Gerade, Beverly Webster, Ann Rastegar, Sarah Denninger, John W. Lee, Janie M. TI A relaxation response training for women undergoing breast biopsy: Exploring integrated care SO BREAST LA English DT Article DE Breast biopsy; Breast cancer screening; Anxiety; Stress; Mind body medicine; Relaxation response ID FALSE-POSITIVE MAMMOGRAMS; SERVICES TASK-FORCE; PERCEIVED STRESS; CANCER; UNCERTAINTY; DIAGNOSIS; DISTRESS; ANXIETY; TRIAL; RISK AB Background: Recent changes in clinical guideline recommendations for age of breast cancer screening initiation highlighted the potential psychological ramifications associated with screening. This study examined the feasibility, acceptability, and preliminary efficacy of a brief Relaxation Response training (RRT) to decrease distress among women undergoing breast biopsy. Methods: Women scheduled for percutaneous core-needle biopsy were recruited into a single-arm RRT trial, including 3 individual sessions. Psychosocial assessments were completed pre- and postintervention. Results: Forty women were enrolled between 6/1/10 and 8/31/11. Among enrollees, 75% completed all 3 RRT sessions, and 75% completed the post-assessment. Participants showed significant reductions in acute distress following each RRT session. Qualitative feedback indicated a positive impact of RRT on clinic care experiences. Conclusions: RRT is a portable intervention that was feasible to implement, acceptable to patients and associated with significant decreases in acute emotional distress during the period of diagnostic uncertainty related to percutaneous breast biopsy. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Park, Elyse R.; Traeger, Lara] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Park, Elyse R.] Massachusetts Gen Hosp, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Park, Elyse R.; Willett, Jessica; Webster, Ann; Rastegar, Sarah; Denninger, John W.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Gerade, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Janie M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM epark@partners.org FU CDC [5 R01 DP000339, K07CA128816] FX CDC: 5 R01 DP000339 (ERP), K07CA128816 (JML). NR 29 TC 1 Z9 1 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2013 VL 22 IS 5 BP 799 EP 805 DI 10.1016/j.breast.2013.02.012 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 219OO UT WOS:000324516800037 PM 23587450 ER PT J AU Trebicka, E Jacob, S Pirzai, W Hurley, BP Cherayil, BJ AF Trebicka, Estela Jacob, Susan Pirzai, Waheed Hurley, Bryan P. Cherayil, Bobby J. TI Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID NONTYPHOIDAL SALMONELLA; SECRETED PROTEIN; EPITHELIAL-CELLS; O ANTIGEN; COMPLEMENT; INFECTIONS; VIRULENCE; AFRICA; CHAIN; ASPARAGINE AB Recent observations from Africa have rekindled interest in the role of serum bactericidal antibodies in protecting against systemic infection with Salmonella enterica serovar Typhimurium. To determine whether the findings are applicable to other populations, we analyzed serum samples collected from healthy individuals in the United States. We found that all but 1 of the 49 adult samples tested had robust bactericidal activity against S. Typhimurium in a standard in vitro assay. The activity was dependent on complement and could be reproduced by immunoglobulin G (IgG) purified from the sera. The bactericidal activity was inhibited by competition with soluble lipopolysaccharide (LPS) from S. Typhimurium but not from Escherichia coli, consistent with recognition of a determinant in the O-antigen polysaccharide. Sera from healthy children aged 10 to 48 months also had bactericidal activity, although it was significantly less than in the adults, correlating with lower levels of LPS-specific IgM and IgG. The lone sample in our collection that lacked bactericidal activity was able to inhibit killing of S. Typhimurium by the other sera. The inhibition correlated with the presence of an LPS-specific IgM and was associated with decreased complement deposition on the bacterial surface. Our results indicate that healthy individuals can have circulating antibodies to LPS that either mediate or inhibit killing of S. Typhimurium. The findings contrast with the observations from Africa, which linked bactericidal activity to antibodies against an S. Typhimurium outer membrane protein and correlated the presence of inhibitory anti-LPS antibodies with human immunodeficiency virus infection. C1 [Trebicka, Estela; Jacob, Susan; Pirzai, Waheed; Hurley, Bryan P.; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. EM cherayil@helix.mgh.harvard.edu FU National Institutes of Health [R01AI089700, R01AI095338]; Clinical Nutrition Research Center at Harvard [P30DK040561] FX This work was supported by National Institutes of Health grants R01AI089700 and R01AI095338 to B.J.C. and B.P.H., respectively, and by the Clinical Nutrition Research Center at Harvard (grant P30DK040561 to W. Allan Walker). NR 41 TC 24 Z9 24 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2013 VL 20 IS 10 BP 1491 EP 1498 DI 10.1128/CVI.00289-13 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 224TG UT WOS:000324911700002 PM 23803904 ER PT J AU Alam, MM Leung, DT Akhtar, M Nazim, M Akter, S Uddin, T Khanam, F Al Mahbuba, D Ahmad, SM Bhuiyan, TR Calderwood, SB Ryan, ET Qadri, F AF Alam, Mohammad Murshid Leung, Daniel T. Akhtar, Marjahan Nazim, Mohammad Akter, Sarmin Uddin, Taher Khanam, Farhana Al Mahbuba, Deena Ahmad, Shaikh Meshbahuddin Bhuiyan, Taufiqur Rahman Calderwood, Stephen B. Ryan, Edward T. Qadri, Firdausi TI Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MEMORY B-CELL; VIBRIO-CHOLERAE; IGG AVIDITY; HOUSEHOLD CONTACTS; CONJUGATE VACCINE; YOUNG-CHILDREN; O1 INFECTION; LIPOPOLYSACCHARIDE; MATURATION; DIARRHEA AB Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies. C1 [Alam, Mohammad Murshid; Leung, Daniel T.; Akhtar, Marjahan; Nazim, Mohammad; Akter, Sarmin; Uddin, Taher; Khanam, Farhana; Al Mahbuba, Deena; Ahmad, Shaikh Meshbahuddin; Bhuiyan, Taufiqur Rahman; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Leung, Daniel T.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI077883, AI058935, AI100923]; Fogarty International Center [TW005572]; Swedish SIDA [B-HN-01-AV]; Thrasher Research Fund Early Career Award; American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund FX This work was supported by the icddr, b, grants from the National Institutes of Health, including grants from the National Institute of Allergy and Infectious Diseases (AI077883 [to E.T.R. and F.Q.], AI058935 [to S.B.C., E.T.R., and F.Q.], and AI100923 [to D.T.L.]), and a training grant in vaccine development from the Fogarty International Center (TW005572 [to M.M.A. and F.Q.]). This study was also supported by Swedish SIDA grant INT-ICDDR, B-HN-01-AV (to F.Q.), a Thrasher Research Fund Early Career Award (to D.T.L.), and a postdoctoral fellowship in tropical infectious diseases from the American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund (to D.T.L.). NR 39 TC 1 Z9 2 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2013 VL 20 IS 10 BP 1541 EP 1548 DI 10.1128/CVI.00341-13 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 224TG UT WOS:000324911700008 PM 23925888 ER PT J AU Rahman, A Rashu, R Bhuiyan, TR Chowdhury, F Khan, AI Islam, K LaRocque, RC Ryan, ET Wrammert, J Calderwood, SB Qadri, F Harris, JB AF Rahman, Atiqur Rashu, Rasheduzzaman Bhuiyan, Taufiqur Rahman Chowdhury, Fahima Khan, Ashraful Islam Islam, Kamrul LaRocque, Regina C. Ryan, Edward T. Wrammert, Jens Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI Antibody-Secreting Cell Responses after Vibrio cholerae O1 Infection and Oral Cholera Vaccination in Adults in Bangladesh SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID IMMUNE-RESPONSES; LIPOPOLYSACCHARIDE; CHILDREN; MUCOSAL; HUMANS; VIRUS AB Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not. C1 [Rahman, Atiqur; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rahman, Atiqur; Rashu, Rasheduzzaman; Bhuiyan, Taufiqur Rahman; Chowdhury, Fahima; Khan, Ashraful Islam; Islam, Kamrul; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. [Rahman, Atiqur] Univ Dhaka, Fac Biol Sci, Dept Biochem & Mol Biol, Dhaka 1000, Bangladesh. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Wrammert, Jens] Emory Univ, Sch Med, Emory Vaccine Ctr, Dept Pediat, Atlanta, GA 30322 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jbharris@partners.org FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, R01 AI099243, K01 TW07409, TW07144]; Charles Hood Foundation; Howard Hughes Medical Institute FX This research was supported by the icddr,b and by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [to S.B.C. and E.T.R.], R03 AI063079 [to F.Q.], U01 AI077883 [to E.T.R.], and R01 AI099243 [to J.B.H.]), as well as Career Development awards (K01 TW07409 [to J.B.H.] and TW07144 [to R.C.L.]), the Charles Hood Foundation (to J.B.H.), and a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R.C.L.). NR 24 TC 11 Z9 11 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2013 VL 20 IS 10 BP 1592 EP 1598 DI 10.1128/CVI.00347-13 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 224TG UT WOS:000324911700015 PM 23945156 ER PT J AU Abraham, NS Richardson, P Castillo, D Kane, SV AF Abraham, Neena S. Richardson, Peter Castillo, Diana Kane, Sunanda V. TI Dual Therapy With Infliximab and Immunomodulator Reduces One-Year Rates of Hospitalization and Surgery Among Veterans With Inflammatory Bowel Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Remicade; Imuran; Anti-Tumor Necrosis Factor (TNF)-alpha; Patient Management; Therapeutic Strategy ID QUALITY-OF-LIFE; CROHNS-DISEASE; MAINTENANCE THERAPY; ULCERATIVE-COLITIS; COMBINATION THERAPY; CERTOLIZUMAB PEGOL; PROPENSITY SCORE; CHARM TRIAL; ADALIMUMAB; REMISSION AB BACKGROUND & AIMS: Effectiveness of early treatment with biologics and immunomodulator therapy on healthcare utilization remains poorly defined. We assessed rates of hospitalization and surgery within 1 year after initiation of infliximab and/or immunomodulator therapy in a United States cohort of patients with inflammatory bowel disease. METHODS: We conducted a retrospective, observational cohort study of veterans with Crohn's disease or ulcerative colitis by using administrative data from 176 Department of Veteran Affairs facilities (October 1, 2001 through September 30, 2009). Inpatient, outpatient, and death records were linked longitudinally with prescription fill data. Each person-day of follow-up was assessed for treatment with infliximab, immunomodulators, both (dual therapy), or neither. We calculated drug exposure time and used Poisson and logistic regression analyses to assess outcomes. RESULTS: The cohort of 20,474 patients included 8042 patients with Crohn's disease and 12,432 with ulcerative colitis (93.9% male; 72.5% white; mean age, 60.9 +/- 14.5 years) prescribed infliximab (0.17%), immunomodulator (1.3%), or dual therapy (1.5%). Adjusted models revealed 50% relative reductions in hospitalization among patients who received 9.2 months of immunomodulator monotherapy, 8 months of infliximab, or 7.7 months of dual therapy. A 50% relative reduction in surgery was observed among patients receiving 7 months of infliximab or 5 months of dual therapy. Analysis of dose-response data revealed 73.1% and 92% reductions in risk of hospitalization and surgery, respectively, after 9 months of dual therapy. CONCLUSIONS: On the basis of a retrospective cohort study, dual therapy with infliximab and an immunomodulator for <8 months is associated with significant reductions in hospitalization and surgery within 1 year of the start of therapy. These findings indicate that patients with IBD are more likely to benefit if dual therapy is initiated earlier in their first year of therapy. C1 [Abraham, Neena S.] Baylor Coll Med, Div Gastroenterol & Hepatol, Sect Digest Dis, Houston, TX 77030 USA. [Abraham, Neena S.; Richardson, Peter; Castillo, Diana] Baylor Coll Med, Houston VA Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Kane, Sunanda V.] Mayo Clin, Div Gastroenterol & Hepatol, Coll Med, Scottsdale, AZ 85259 USA. RP Abraham, NS (reprint author), Mayo Clin, Div Gastroenterol, 13400 East Shea Blvd, Scottsdale, AZ 85259 USA. EM abraham.neena@mayo.edu FU Janssen Biotech, Inc. FX Supported by an investigator-initiated grant from Janssen Biotech, Inc. NR 42 TC 9 Z9 9 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2013 VL 11 IS 10 BP 1281 EP 1287 DI 10.1016/j.cgh.2013.06.004 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223QU UT WOS:000324823200016 PM 23792295 ER PT J AU Braunwald, E AF Braunwald, E. TI Heart Failure: An Update SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 5 TC 5 Z9 6 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2013 VL 94 IS 4 BP 430 EP 432 DI 10.1038/clpt.2013.149 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 220IL UT WOS:000324576100014 PM 24048236 ER PT J AU Raab, PA Mackintosh, MA Gros, DF Morland, LA AF Raab, Phillip A. Mackintosh, Margaret-Anne Gros, Daniel F. Morland, Leslie A. TI Influence of Depression on State and Trait Anger in Veterans with Posttraumatic Stress Disorder (vol 37, pg 673, 2013) SO COGNITIVE THERAPY AND RESEARCH LA English DT Correction C1 [Raab, Phillip A.; Mackintosh, Margaret-Anne; Morland, Leslie A.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs Pacific Isl Healthcare Syst, Pacific Isl Div, Honolulu, HI 96819 USA. [Raab, Phillip A.; Mackintosh, Margaret-Anne; Morland, Leslie A.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC 29425 USA. [Morland, Leslie A.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Raab, PA (reprint author), Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs Pacific Isl Healthcare Syst, Pacific Isl Div, 3375 Koapaka,Suite 1-560, Honolulu, HI 96819 USA. EM drewraab@gmail.com NR 1 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD OCT PY 2013 VL 37 IS 5 BP 1089 EP 1090 DI 10.1007/s10608-013-9534-3 PG 2 WC Psychology, Clinical SC Psychology GA 223PD UT WOS:000324817600021 ER PT J AU Cohen, R Caravatto, PP Petry, T Cummings, D AF Cohen, Ricardo Caravatto, Pedro Paulo Petry, Tarissa Cummings, David TI Role of Metabolic Surgery in Less Obese or Non-Obese Subjects with Type 2 Diabetes: Influence Over Cardiovascular Events SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Type 2 diabetes mellitus; Metabolic surgery; Bariatric surgery; Obesity; Gastrointestinal surgery ID GASTRIC BYPASS-SURGERY; BODY-MASS INDEX; LIFE-STYLE INTERVENTION; BARIATRIC SURGERY; WEIGHT-LOSS; MULTIFACTORIAL INTERVENTION; SLEEVE GASTRECTOMY; MEDICAL THERAPY; PREVALENCE; MORTALITY AB Bariatric surgery was initially developed as a tool for weight reduction only, but it is gaining increasing popularity because of its remarkable effect on glucose metabolism in morbidly obese and less obese patients. Recent publications have shown the good results of metabolic surgery, creating a new field of clinical research that is currently overflowing in the medical community with outstanding high-quality data. In morbidly obese population, there is compelling data on long term cardiovascular risk reduction and mortality, coming from longitudinal prospective studies and systematic reviews. Numbers range from 33 to 92 % of decrease in fatal and nonfatal cardiovascular events. In low body mass index (BMI) diabetics, there is an increasing number of reported good outcomes after metabolic surgery with the aim to treat type 2 diabetes (T2DM). There is scarce information on cardiovascular outcomes in non-morbidly obese subjects, but the extraordinary glucose, lipid and blood pressure control in the published series are suggesting good long-term effects on cardiovascular risk profile and mortality. The papers review was comprehensive, including the available randomized controlled trials, long-term prospective series and systematic reviews. C1 [Cohen, Ricardo; Caravatto, Pedro Paulo; Petry, Tarissa] Oswaldo Cruz Hosp, Ctr Excellence Metab & Bariatr Surg, Sao Paulo, Brazil. [Cummings, David] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA USA. [Cummings, David] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Cohen, R (reprint author), Oswaldo Cruz Hosp, Ctr Excellence Metab & Bariatr Surg, Sao Paulo, Brazil. EM ricardo.cohen@haoc.com.br NR 54 TC 4 Z9 4 U1 0 U2 9 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD OCT PY 2013 VL 15 IS 10 AR 355 DI 10.1007/s11883-013-0355-3 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 221EF UT WOS:000324639800001 PM 23955664 ER PT J AU Osborn, EA Jaffer, FA AF Osborn, Eric A. Jaffer, Farouc A. TI Imaging Atherosclerosis and Risk of Plaque Rupture SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Atherosclerosis; Plaque rupture; Molecular imaging; Myocardial infarction; Thrombosis ID OPTICAL COHERENCE TOMOGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; WORKING GROUP; INTRAVASCULAR ULTRASOUND; INTRAPLAQUE HEMORRHAGE; ARTERY-DISEASE; CT ANGIOGRAPHY; INFLAMMATION AB Atherosclerosis imaging strategies can delineate characteristics of plaques at risk of rupture and thrombosis. Structural plaque imaging identifies high-risk plaque features, including lipid pools, thin fibrous caps, and intraplaque hemorrhage. New molecular imaging techniques complement structural imaging approaches by illuminating important features of plaque biology, with a prominent focus on detecting inflammation as a high-risk phenotype. As we unravel the molecular and structural characteristics underlying thrombosis-prone plaques, there is significant promise for eventual early identification and prediction of atherosclerotic plaque complications before they occur. Here we focus on recent imaging insights into high-risk arterial plaques, the etiologic agent of acute myocardial infarction, stroke, and sudden cardiac death. C1 [Osborn, Eric A.] Harvard Univ, Sch Med, Div Cardiol, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Osborn, Eric A.; Jaffer, Farouc A.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Cardiol Div,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Cardiol Div,Massachusetts Gen Hosp, Simches Res Bldg 3206,185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu FU NIH [R01 HL108229]; MGH SPARK Award; American Heart Association [13GRNT1760040] FX NIH R01 HL108229, MGH SPARK Award, American Heart Association Grant-in-Aid 13GRNT1760040. NR 41 TC 5 Z9 5 U1 0 U2 10 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD OCT PY 2013 VL 15 IS 10 AR 359 DI 10.1007/s11883-013-0359-z PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 221EF UT WOS:000324639800005 PM 23982263 ER PT J AU Motiwala, SR Szymonifka, J Belcher, A Weiner, RB Baggish, AL Sluss, P Gaggin, HK Bhardwaj, A Januzzi, JL AF Motiwala, Shweta R. Szymonifka, Jackie Belcher, Arianna Weiner, Rory B. Baggish, Aaron L. Sluss, Patrick Gaggin, Hanna K. Bhardwaj, Anju Januzzi, James L. TI Serial measurement of galectin-3 in patients with chronic heart failure: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Biomarkers; Galectin-3; Outcomes; Prognosis; Remodelling ID NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT; DYSFUNCTION; ASSOCIATION; MORTALITY; OUTCOMES; DYSPNEA AB Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF. A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 3 months. The amount of time spent with a galectin-3 level 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P 0.03; 21.7 vs. 16.5 ng/mL, P 0.03; 23.2 vs. 16.0 ng/mL, P 0.007). Galectin-3 concentration changed in 35.2 of subjects during study procedures; time spent at 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) 0.90; P 0.05], and predicted increase in LV ejection fraction (OR 1.20; P 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P 0.02). There were no significant effects of medications on galectin-3 levels. In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels. C1 [Motiwala, Shweta R.; Szymonifka, Jackie; Belcher, Arianna; Weiner, Rory B.; Baggish, Aaron L.; Gaggin, Hanna K.; Bhardwaj, Anju; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sluss, Patrick] Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU BG Medicine; Dennis and Marilyn Barry Fellowship in Cardiology; Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment FX A grant from BG Medicine. The study sponsor had no role in data analysis or manuscript preparation. S.R.M. is supported by the Dennis and Marilyn Barry Fellowship in Cardiology, H.K.G. is supported in part by the Clark Fund for Cardiac Research Innovation. J.L.J. is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment. NR 14 TC 39 Z9 40 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD OCT PY 2013 VL 15 IS 10 BP 1157 EP 1163 DI 10.1093/eurjhf/hft075 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 228HD UT WOS:000325175700011 PM 23666680 ER PT J AU Kwee, TC Cheng, G Lam, MGEH Basu, S Alavi, A AF Kwee, Thomas C. Cheng, Gang Lam, Marnix G. E. H. Basu, Sandip Alavi, Abass TI SUVmax of 2.5 should not be embraced as a magic threshold for separating benign from malignant lesions SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material ID DUAL TIME-POINT; PARTIAL VOLUME CORRECTION; STANDARDIZED UPTAKE VALUE; FDG-PET; INDETERMINATE BIOPSY; METABOLIC BIOPSY; NODULES; TOOL C1 [Kwee, Thomas C.; Lam, Marnix G. E. H.] Univ Med Ctr Utrecht, Dept Radiol & Nucl Med, Utrecht, Netherlands. [Cheng, Gang] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA USA. [Cheng, Gang; Alavi, Abass] Hosp Univ Penn, Dept Radiol, Div Nucl Med, Philadelphia, PA 19104 USA. [Basu, Sandip] Tata Mem Ctr Annexe, Bhabha Atom Res Ctr, Radiat Med Ctr, Bombay, Maharashtra, India. RP Alavi, A (reprint author), Hosp Univ Penn, Dept Radiol, Div Nucl Med, 3400 Spruce St,110 Donner Bldg, Philadelphia, PA 19104 USA. EM abass.alavi@uphs.upenn.edu NR 17 TC 11 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2013 VL 40 IS 10 BP 1475 EP 1477 DI 10.1007/s00259-013-2484-x PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 221GE UT WOS:000324645100001 PM 23801170 ER PT J AU Wang, L Ma, J Manson, JE Buring, JE Gaziano, JM Sesso, HD AF Wang, Lu Ma, Jing Manson, Joann E. Buring, Julie E. Gaziano, J. Michael Sesso, Howard D. TI A prospective study of plasma vitamin D metabolites, vitamin D receptor gene polymorphisms, and risk of hypertension in men SO EUROPEAN JOURNAL OF NUTRITION LA English DT Article DE Vitamin D; Polymorphisms; Prospective study; Hypertension; Men ID RENIN-ANGIOTENSIN SYSTEM; 25-HYDROXYVITAMIN D LEVELS; LONG-TERM TREATMENT; BLOOD-PRESSURE; INCIDENT HYPERTENSION; 1,25-DIHYDROXYVITAMIN D-3; PARATHYROID-HORMONE; PHYSICIANS HEALTH; D SUPPLEMENTATION; D ALPHACALCIDOL AB Laboratory studies have suggested that vitamin D inadequacy may be implicated in development of hypertension. Evidence from epidemiologic studies remains limited. We aim to examine the prospective associations of circulating vitamin D metabolites, vitamin D receptor (VDR) gene polymorphisms, and their interaction with risk of hypertension. We conducted prospective analyses among 1,211 US men that were free of baseline hypertension and had baseline plasma 25hydroxy-vitamin D (25(OH)D) or 1,25dihydroxy-vitamin D (1,25(OH)(2)D) measured and VDR BsmI or FokI polymorphisms genotyped. During 15.3-year follow-up, 695 men developed incident hypertension. After multivariable adjustment, the hazard ratios (HRs) and 95 % CIs for hypertension across increasing quartiles of plasma vitamin D metabolites were 1.00 (ref), 0.94 (0.69-1.27), 0.69 (0.50-0.96), and 0.82 (0.60-1.13) for 25(OH)D (p, trend: 0.43), and 1.00, 0.92 (0.66-1.27), 1.12 (0.82-1.54), and 1.19 (0.86-1.63) for 1,25(OH)(2)D (p, trend: 0.16). Compared with carriers of VDR BsmI bb, carriers of bB or BB had a HR of 1.25 (1.04-1.51) for hypertension. For VDR FokI polymorphism, compared with carriers of FF and Ff combined, carriers of ff had a HR of 1.32 (1.03-1.70). The relation between plasma 25(OH)D and risk of hypertension did not differ by VDR BsmI and FokI polymorphisms. In a prospective cohort of men, we found suggestive evidence for an inverse association between plasma 25(OH)D and risk of hypertension. We also found associations between VDR BsmI and FokI polymorphisms with hypertension risk. More research is needed to further determine the role of vitamin D in hypertension prevention. C1 [Wang, Lu; Manson, Joann E.; Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. [Ma, Jing] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. [Manson, Joann E.; Buring, Julie E.; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. RP Wang, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave East, Boston, MA 02215 USA. EM luwang@rics.bwh.harvard.edu FU National Institutes of Health, Bethesda, MD [CA 097193, CA 042182, CA 058684, CA 034944, CA 040360, HL 026490, HL 034595, HL 095649]; National Heart, Lung, and Blood Institutes [HL095649] FX The authors acknowledge the crucial contributions of the entire staff of the PHS. We are also indebted to the 22,071 dedicated and committed participants randomized into the PHS starting in 1982. The study was supported in part by grants (CA 097193, CA 042182, CA 058684, CA 034944, CA 040360, HL 026490, HL 034595, HL 095649) from the National Institutes of Health, Bethesda, MD. Dr. Wang was supported by a career development grant HL095649 from the National Heart, Lung, and Blood Institutes. NR 37 TC 21 Z9 23 U1 1 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1436-6207 J9 EUR J NUTR JI Eur. J. Nutr. PD OCT PY 2013 VL 52 IS 7 BP 1771 EP 1779 DI 10.1007/s00394-012-0480-8 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 223TL UT WOS:000324833000008 PM 23262750 ER PT J AU Falk, SJ Dizon, DS AF Falk, Sandy J. Dizon, Don S. TI Sexual dysfunction in women with cancer SO FERTILITY AND STERILITY LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; VERSUS-HOST-DISEASE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; MENOPAUSAL SYMPTOMS; ENDOMETRIAL CANCER; STAGE-I; DIAGNOSIS; CHEMOTHERAPY; ASSOCIATION AB Approximately 14 million people have a history of cancer in the United States alone, and the number is expected to increase with time. This has prompted an appreciation of the quality of life for survivors. Women treated for cancer identify gynecologic issues as a major concern for both general health and the negative impact on sexual function that follow the cancer diagnosis and subsequent treatment. Unfortunately, issues related to sexual health continue to be underappreciated. Although comprehensive cancer centers have adopted specialized centers for survivorship issues, including those involving sexual health, consultations are not widely available in most communities. We provide background information on female sexual health, examine the impact of cancer treatment on sexual function, and discuss some of the major sexual health issues of women who have received a cancer diagnosis and been subsequently treated. (Fertil Steril (R) 2013; 100: 916-21. (C) 2013 by American Society for Reproductive Medicine.) C1 [Falk, Sandy J.] Dana Farber Canc Inst, Sexual Hlth Program, Boston, MA 02115 USA. [Falk, Sandy J.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Med, Cambridge, MA 02138 USA. [Dizon, Don S.] Harvard Univ, Sch Med, Dept Internal Med, Cambridge, MA 02138 USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Falk, SJ (reprint author), Dana Farber Canc Inst, Adult Survivorship Program, 450 Brookline Ave, Boston, MA 02215 USA. EM sfalk@partners.org NR 44 TC 14 Z9 14 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2013 VL 100 IS 4 BP 916 EP 921 DI 10.1016/j.fertnstert.2013.08.018 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 225WG UT WOS:000324995200017 PM 24011609 ER PT J AU Gora, MJ Sauk, JS Carruth, RW Lu, W Carlton, DT Soomro, A Rosenberg, M Nishioka, NS Tearney, GJ AF Gora, Michalina J. Sauk, Jenny S. Carruth, Robert W. Lu, Weina Carlton, Drew T. Soomro, Amna Rosenberg, Mireille Nishioka, Norman S. Tearney, Guillermo J. TI Imaging the Upper Gastrointestinal Tract in Unsedated Patients Using Tethered Capsule Endomicroscopy SO GASTROENTEROLOGY LA English DT Editorial Material ID OPTICAL COHERENCE TOMOGRAPHY C1 [Gora, Michalina J.; Carruth, Robert W.; Lu, Weina; Carlton, Drew T.; Soomro, Amna; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gora, Michalina J.; Carruth, Robert W.; Lu, Weina; Carlton, Drew T.; Soomro, Amna; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA USA. [Sauk, Jenny S.; Nishioka, Norman S.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, England. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, BHX 604A, Boston, MA 02114 USA. EM gtearney@partners.org FU NCI NIH HHS [R01CA103769, R01 CA103769]; NIDDK NIH HHS [R01 DK091923, P30 DK043351, R01DK091923] NR 7 TC 7 Z9 7 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2013 VL 145 IS 4 BP 723 EP 725 DI 10.1053/j.gastro.2013.07.053 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 219AE UT WOS:000324474600013 PM 23932950 ER PT J AU Perencevich, M Ojha, RP Steyerberg, EW Syngal, S AF Perencevich, Molly Ojha, Rohit P. Steyerberg, Ewout W. Syngal, Sapna TI Racial and Ethnic Variations in the Effects of Family History of Colorectal Cancer on Screening Compliance SO GASTROENTEROLOGY LA English DT Article DE Population Study; Database Analysis; Early Detection; Colon Cancer Prevention ID RANDOMIZED-CONTROLLED-TRIAL; MEDICAL-RECORD AUDIT; 1ST-DEGREE RELATIVES; AMERICAN-COLLEGE; AFRICAN-AMERICANS; HEALTH BEHAVIORS; COLON-CANCER; RISK; POPULATION; SURVEILLANCE AB BACKGROUND & AIMS: Individuals with a family history of colorectal cancer (CRC) have a higher risk of developing CRC than the general population, and studies have shown that they are more likely to undergo CRC screening. We assessed the overall and race-and ethnicity-specific effects of a family history of CRC on screening. METHODS: We analyzed data from the 2009 California Health Interview Survey to estimate overall and race-and ethnicity-specific odds ratios (ORs) for the association between family history of CRC and CRC screening. RESULTS: The unweighted and weighted sample sizes were 23,837 and 8,851,003, respectively. Individuals with a family history of CRC were more likely to participate in any form of screening (OR, 2.3; 95% confidence limit [CL], 1.7, 3.1) and in colonoscopy screening (OR, 2.7; 95% CL, 2.2, 3.4) than those without a family history, but this association varied among racial and ethnic groups. The magnitude of the association between family history and colonoscopy screening was highest among Asians (OR, 6.1; 95% CL, 3.1, 11.9), lowest among Hispanics (OR, 1.4; 95% CL, 0.67, 2.8), and comparable between non-Hispanic whites (OR, 3.1; 95% CL, 2.6, 3.8) and non-Hispanic blacks (OR 2.6; 95% CL, 1.2, 5.7) (P for interaction < .001). CONCLUSIONS: The effects of family history of CRC on participation in screening vary among racial and ethnic groups, and have the lowest effects on Hispanics, compared with other groups. Consequently, interventions to promote CRC screening among Hispanics with a family history should be considered. C1 [Perencevich, Molly; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02215 USA. [Perencevich, Molly; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Ojha, Rohit P.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Steyerberg, Ewout W.] Erasmus MC, Ctr Med Decis Making, Dept Publ Hlth, Rotterdam, Netherlands. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Syngal, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gastroenterol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM Sapna_syngal@dfci.harvard.edu OI Ojha, Rohit/0000-0003-0595-8990; Steyerberg, Ewout/0000-0002-7787-0122 FU National Institutes of Health [5T32DK007533-27, K24CA11343] FX Supported by an institutional T32 grant (5T32DK007533-27 to M. P.) and by a K24 grant (K24CA11343 to S. S.) from the National Institutes of Health. NR 76 TC 7 Z9 7 U1 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2013 VL 145 IS 4 BP 775 EP + DI 10.1053/j.gastro.2013.06.037 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 219AE UT WOS:000324474600023 PM 23796457 ER PT J AU Koukos, G Polytarchou, C Kaplan, JL Morley-Fletcher, A Gras-Miralles, B Kokkotou, E Baril-Dore, M Pothoulakis, C Winter, HS Iliopoulos, D AF Koukos, Georgios Polytarchou, Christos Kaplan, Jess L. Morley-Fletcher, Alessio Gras-Miralles, Beatriz Kokkotou, Efi Baril-Dore, Mariah Pothoulakis, Charalabos Winter, Harland S. Iliopoulos, Dimitrios TI MicroRNA-124 Regulates STAT3 Expression and Is Down-regulated in Colon Tissues of Pediatric Patients With Ulcerative Colitis SO GASTROENTEROLOGY LA English DT Article DE IL6; BCLXL; Let-7; Gene Regulation ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; DNA METHYLATION; MULTIPLE-SCLEROSIS; PATHOGENESIS; CANCER; IDENTIFICATION; ACTIVATION; INVOLVEMENT; ONCOGENESIS AB BACKGROUND & AIMS: Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC). METHODS: We used a library of 316 miRs to identify those that regulate phosphorylation of signal transducer and activator of transcription 3 (STAT3) in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time polymerase chain reaction analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2'-deoxycytidine (5-AZA). Methylation of the MIR124 promoter was measured by quantitative methylation-specific polymerase chain reaction. RESULTS: Levels of phosphorylated STAT3 and the genes it regulates (encoding vascular endothelial growth factor (VEGF), BCL2, BCLXL, and matrix metallopeptidase 9 [MMP9]) were increased in pediatric patients with UC compared with control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by >= 75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was down-regulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 messenger RNA (mRNA). Levels of miR-124 were decreased, whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC compared with those with inactive disease. In addition, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Down-regulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-AZA up-regulated miR-124 and reduced levels of STAT3 mRNA. CONCLUSIONS: miR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and the pathogenesis of UC in children. C1 [Koukos, Georgios; Polytarchou, Christos; Iliopoulos, Dimitrios] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Div Digest Dis, Los Angeles, CA 90095 USA. [Koukos, Georgios; Polytarchou, Christos; Iliopoulos, Dimitrios] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Med, Los Angeles, CA 90095 USA. [Koukos, Georgios; Polytarchou, Christos; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kaplan, Jess L.; Morley-Fletcher, Alessio; Baril-Dore, Mariah; Winter, Harland S.] Mass Gen Hosp Children, Pediat IBD Ctr, Boston, MA USA. [Gras-Miralles, Beatriz; Kokkotou, Efi] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. [Pothoulakis, Charalabos] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Inflammatory Bowel Dis Ctr, Los Angeles, CA 90095 USA. RP Iliopoulos, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Div Digest Dis, 650 Charles E Young Dr South,CHS 44-133, Los Angeles, CA 90095 USA. EM diliopoulos@mednet.ucla.edu RI Koukos, Georgios/B-1544-2009; OI Koukos, Georgios/0000-0002-9470-0651; Gras-Miralles, Beatriz/0000-0002-5943-7755 FU Charles H. Hood Foundation; NIH [DK60729]; Pediatric IBD Foundation FX This study was supported by the Charles H. Hood Foundation (DI), NIH DK60729 (C.Pothoulakis), a grant from the Pediatric IBD Foundation (HSW), and philanthropic support from Martin Schlaff (HSW). NR 44 TC 65 Z9 66 U1 4 U2 27 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2013 VL 145 IS 4 BP 842 EP + DI 10.1053/j.gastro.2013.07.001 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 219AE UT WOS:000324474600030 PM 23856509 ER PT J AU Cooper, JN Fried, L Tepper, P Barinas-Mitchell, E Conroy, MB Evans, RW Brooks, MM Woodard, GA Sutton-Tyrrell, K AF Cooper, Jennifer N. Fried, Linda Tepper, Ping Barinas-Mitchell, Emma Conroy, Molly B. Evans, Rhobert W. Brooks, Maria Mori Woodard, Genevieve A. Sutton-Tyrrell, Kim TI Changes in serum aldosterone are associated with changes in obesity-related factors in normotensive overweight and obese young adults SO HYPERTENSION RESEARCH LA English DT Article DE adipokines; adipose tissue; aldosterone; metabolic syndrome; obesity ID RENIN-ANGIOTENSIN SYSTEM; BLOOD-PRESSURE; WEIGHT-LOSS; PLASMA-ALDOSTERONE; METABOLIC SYNDROME; ADIPOSE-TISSUE; INSULIN-RESISTANCE; MINERALOCORTICOID RECEPTOR; SCIENTIFIC STATEMENT; NERVOUS-SYSTEM AB Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index >= 25 and<40 kg m(-2), age 20-45 years) in a clinical trial examining the effects of a 1-year diet and physical activity intervention with or without sodium restriction on vascular health. Body weight, serum aldosterone, 24-h sodium and potassium excretion and obesity-related factors were measured at baseline, 6, 12 and 24 months. Weight loss was significant at 6 (7%), 12 (6%) and 24 months (4%; all P<0.0001). Decreases in aldosterone were associated with decreases in C-reactive protein, leptin, insulin, homeostasis assessment of insulin resistance, heart rate, tonic cardiac sympathovagal balance and increases in adiponectin (all P<0.05) in models adjusting for baseline age, sex, race, intervention arm, time since baseline, and sodium and potassium excretion. Weight loss and reductions in thigh intermuscular fat (intermuscular adipose tissue area; IMAT) were associated with decreases in aldosterone in the subgroup (n = 98) with metabolic syndrome (MetS) at baseline (MetS x weight loss, P = 0.04; MetS x change in IMAT, P 0.04). Favorable changes in obesity-related factors are associated with reductions in aldosterone in young adults with no risk factors besides excess weight, an important finding, given aldosterone's emergence as an important cardiometabolic risk factor. C1 [Cooper, Jennifer N.; Fried, Linda; Tepper, Ping; Barinas-Mitchell, Emma; Conroy, Molly B.; Evans, Rhobert W.; Brooks, Maria Mori; Woodard, Genevieve A.; Sutton-Tyrrell, Kim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Cooper, Jennifer N.; Brooks, Maria Mori] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Fried, Linda] VA Pittsburgh Healthcare Syst, Univ Dr Div, Pittsburgh, PA USA. [Conroy, Molly B.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15261 USA. RP Cooper, JN (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Epidemiol Data Ctr, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM jennifer.njoroge@gmail.com OI Brooks, Maria/0000-0002-2030-7873; Barinas-Mitchell, Emma/0000-0002-7280-7781 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL077525, F31 HL106986] FX This work was supported by Grants R01 HL077525 and F31 HL106986 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. We thank Beth Hauth for expert laboratory analyses. We greatly appreciate the efforts of the SAVE trial volunteers and the study and clinic coordinators (Laura Kinzel and Eileen Cole). NR 42 TC 9 Z9 9 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD OCT PY 2013 VL 36 IS 10 BP 895 EP 901 DI 10.1038/hr.2013.45 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 230GR UT WOS:000325325600013 PM 23657296 ER PT J AU Indic, P Paydarfar, D Barbieri, R AF Indic, Premananda Paydarfar, David Barbieri, Riccardo TI Point Process Modeling of Interbreath Interval: A New Approach for the Assessment of Instability of Breathing in Neonates SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Infant apnea; lognormal distribution; point processes; prematurity; respiratory rhythm; time-frequency analysis ID HEART-RATE; INFANTS; DYNAMICS; PATTERNS; PRETERM; RHYTHM; APNEA AB Interbreath interval (IBI), the time interval between breaths, is an important measure used to analyze irregular breathing patterns in neonates. The discrete bursts of neural activity generate the IBI time series, which exhibits stochastic as well as deterministic dynamics. To quantify the irregularity of breathing, we propose a point process model of IBI using a comprehensive stochastic dynamic modeling framework. The IBIs of immature breathing patterns exhibit a long tail distribution and within a point process model, we have considered the lognormal distribution to represent the stochastic IBI characteristics. An autoregressive (AR) function is embedded within the model to capture the short-term IBI dynamics including abrupt IBI prolongations related to sporadic and periodic apneas that are common in neonates. We tested the utility of our paradigm for depicting the respiratory dynamics in neonatal rats and in preterm infants. Kolmogorov-Smirnov (KS) and independence tests reveal that the model accurately tracks the dynamic characteristics of the signals. In preterm infants, our model-derived indices of IBI instability strongly correlate with clinically derived indices of maturation. Our results validate a new class of algorithms, based on the point process theory, for defining instantaneous measures of breathing irregularity in neonates. C1 [Indic, Premananda; Paydarfar, David] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Paydarfar, David] Harvard Univ, Wyss Inst, Boston, MA 02115 USA. [Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Sch Med, Boston, MA 02114 USA. [Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Indic, P (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. EM Premananda.Indic@umassmed.edu; David.Paydarfar@umassmed.edu; barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833 FU Hansjorg Wyss Institute for Biologically Inspired Engineering at Harvard University; National Institutes of Health [R01-HL084502, R01-HL49848, R01-HL071884, R01-GM104987] FX Manuscript received January 14, 2013; revised April 15, 2013; accepted May 9, 2013. Date of publication May 31, 2013; date of current version September 14, 2013. This work was supported in part by the Hansjorg Wyss Institute for Biologically Inspired Engineering at Harvard University and in part by the National Institutes of Health under Grant R01-HL084502, Grant R01-HL49848, Grant R01-HL071884, Grant R01-GM104987. Asterisk indicates corresponding author. NR 21 TC 4 Z9 4 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 2013 VL 60 IS 10 BP 2858 EP 2866 DI 10.1109/TBME.2013.2264162 PG 9 WC Engineering, Biomedical SC Engineering GA 223ST UT WOS:000324830800020 PM 23739777 ER PT J AU Souayah, N Noopur, R Tick-Chong, PS AF Souayah, Nizar Noopur, Raje Tick-Chong, Peter Siao TI Beneficial effects of Rituximab in patients with anti-MAG (myelin-associated glycoprotein) neuropathy: case reports SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article DE Anti MAG antibody; ataxia; IVIG; neuropathy; Rituximab ID IGM M-PROTEINS; MONOCLONAL IGM; POLYNEUROPATHY; ANTIBODIES AB Anti-myelin-associated glycoprotein (MAG) neuropathy is a primary demyelinating sensorimotor polyneuropathy that can be very debilitating and is known to be resistant to treatment. There are only a few conflicting reports on the effect of Rituximab in anti-MAG neuropathy. We present three patients who improved remarkably with Rituximab infusions. Until the safety and efficacy of this drug are determined in larger controlled studies, use of Rituximab should be limited to patients with significant neurologic deficits. C1 [Souayah, Nizar] Univ Med & Dent New Jersey, Dept Neurol & Neurosci, Newark, NJ 07101 USA. [Noopur, Raje] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. [Tick-Chong, Peter Siao] Boston Univ, Dept Neurol, Boston, MA 02215 USA. RP Souayah, N (reprint author), Univ Med & Dent New Jersey, Dept Neurol & Neurosci, 90 Bergen St,DOC 8128, Newark, NJ 07101 USA. EM souayani@umdnj.edu NR 17 TC 2 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PD OCT PY 2013 VL 35 IS 5 BP 622 EP 624 DI 10.3109/08923973.2013.822507 PG 3 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 222YK UT WOS:000324768800011 PM 23944288 ER PT J AU Nelson, BC Borok, MZ Mhlanga, TO Makadzange, AT Campbell, TB AF Nelson, Bradley C. Borok, Margaret Z. Mhlanga, Tafadzwa O. Makadzange, Azure T. Campbell, Thomas B. TI AIDS-associated Kaposi sarcoma: outcomes after initiation of antiretroviral therapy at a university-affiliated hospital in urban Zimbabwe SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Kaposi sarcoma; HIV; AIDS; Antiretroviral therapy ID TREATMENT PROGRAMS; EARLY MORTALITY; HUMAN-HERPESVIRUS-8; CANCER; AFRICA; ADULTS; SEROPREVALENCE; EPIDEMIOLOGY; POPULATION; MALAWI AB Objective: To retrospectively investigate the outcomes of patients with AIDS-associated Kaposi sarcoma (AIDS-KS) after initiation of antiretroviral therapy (ART), under routine practice conditions, at a university-affiliated hospital in urban Zimbabwe. Background: While studies from developed nations have demonstrated excellent outcomes for AIDS-KS patients treated with ART, few studies have examined the outcomes of African AIDS-KS patients after starting therapy. Methods: A retrospective cohort of 124 AIDS patients initiating ART under routine practice conditions was studied. Thirty-one patients with AIDS-KS were matched 1:3 to 93 AIDS patients without KS (non-KS). The primary outcome was loss-to-care after initiation of therapy. Multivariate analysis was performed to identify significant predictors of loss-to-care. The percent change in weight at 6 months after starting ART was a secondary outcome. A sub-group analysis evaluated differences in pretreatment variables between AIDS-KS patients retained-in-care compared to those lost-to-care. Results: AIDS-KS patients had significantly greater 2-year proportional loss-to-care than matched non-KS AIDS patients (26.4% vs. 9.5%; p = 0.01) after initiation of ART. In multivariate analysis, the presence of KS (p = 0.02) was the only significant predictor of loss-to-care. AIDS-KS patients had significantly less weight gain after starting ART than non-KS AIDS patients (+3.4% vs. +6.4%; p = 0.03). AIDS-KS patients retained-in-care had significantly higher pre-treatment CD4+ lymphocyte counts than AIDS-KS patients lost-to-care (223 vs. 110 cells/mm(3); p = 0.04). Conclusions: In this retrospective study, AIDS-KS patients experienced significantly worse outcomes than matched non-KS AIDS patients after initiation of ART. AIDS-KS patients with higher pre-treatment CD4+ lymphocyte counts were more likely to be retained in care. (C) 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Nelson, Bradley C.] Univ Calif San Diego Hlth Syst, Dept Med, Div Cardiovasc Dis, La Jolla, CA 92107 USA. [Nelson, Bradley C.; Campbell, Thomas B.] Univ Colorado, Sch Med, Dept Med, Div Infect Dis, Denver, CO USA. [Borok, Margaret Z.; Mhlanga, Tafadzwa O.; Makadzange, Azure T.] Univ Zimbabwe, Coll Hlth Sci, Dept Med, Harare, Zimbabwe. [Makadzange, Azure T.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Nelson, BC (reprint author), Univ Calif San Diego Hlth Syst, Dept Med, Div Cardiovasc Dis, 9444 Med Ctr Dr, La Jolla, CA 92107 USA. EM b4nelson@ucsd.edu FU William Robinson-Peter Durst International Healthcare Scholarship; University of Zimbabwe Department of Medicine FX Sources of support: This study was supported by grants from the William Robinson-Peter Durst International Healthcare Scholarship and the University of Zimbabwe Department of Medicine. NR 26 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD OCT PY 2013 VL 17 IS 10 BP E902 EP E906 DI 10.1016/j.ijid.2013.04.011 PG 5 WC Infectious Diseases SC Infectious Diseases GA 219AP UT WOS:000324476200018 PM 23809198 ER PT J AU Choi, HR Anderson, D Foster, S Beal, M Lee, JA Barr, C Malchau, H McCarthy, J Kwon, YM AF Choi, Ho-Rim Anderson, David Foster, Scott Beal, Matthew Lee, Jo Ann Barr, Christopher Malchau, Henrik McCarthy, Joseph Kwon, Young-Min TI Acetabular cup positioning in revision total hip arthroplasty with Paprosky type III acetabular defects: Martell radiographic analysis SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Total hip arthroplasty; Revision; Acetabular bone defect; Paprosky type III; Cup position; Martell technique ID FOLLOW-UP; COMPONENT; PLACEMENT; RECONSTRUCTION; ACCURACY; CLASSIFICATION; REPLACEMENT; MANAGEMENT; NAVIGATION AB This study evaluates acetabular cup position in the setting of revision total hip arthroplasty (THA) with severe acetabular bone defects. With a definition of safe zone of abduction (30-50A degrees) and anteversion (5-25A degrees), acetabular cup position was measured by a digital image analysis program for 34 patients with Paprosky type III acetabular bone defects. There were 24 cups (71 %) for abduction and 26 cups (76 %) for anteversion located in the safe zone. Nineteen cups (56 %) were within the safe zone for both abduction and anteversion. There was no dislocation, however one cup out of the safe zone resulted in early cup failure due to aseptic loosening. The acetabular cup positioning in patients with Paprosky type III defects was 'optimal' in half of the cases. The prevalence of optimal acetabular cup position was similar to those reported in primary THA, suggesting that the presence of a large acetabular bone defect may not be a significant risk factor for suboptimal acetabular cup positioning in the setting of revision THA. C1 [Choi, Ho-Rim; Anderson, David; Foster, Scott; Beal, Matthew; Lee, Jo Ann; Barr, Christopher; Malchau, Henrik; McCarthy, Joseph; Kwon, Young-Min] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM kwon.young-min@mgh.harvard.edu OI Malchau, Henrik/0000-0002-4291-2441 NR 26 TC 10 Z9 12 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD OCT PY 2013 VL 37 IS 10 BP 1905 EP 1910 DI 10.1007/s00264-013-2008-0 PG 6 WC Orthopedics SC Orthopedics GA 221IR UT WOS:000324652000006 PM 23881062 ER PT J AU Richter, HE Morgan, SL Gleason, JL Szychowski, JM Goode, PS Burgio, KL AF Richter, Holly E. Morgan, Sarah L. Gleason, Jonathan L. Szychowski, Jeff M. Goode, Patricia S. Burgio, Kathryn L. TI Pelvic floor symptoms and bone mineral density in women undergoing osteoporosis evaluation SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Pelvic floor disorders; Bone mineral density; Pathophysiology ID STRESS URINARY-INCONTINENCE; FECAL INCONTINENCE; ORGAN PROLAPSE; OLDER WOMEN; QUESTIONNAIRES; PREVALENCE; DISORDERS; ADULTS; TRENDS; ICIQ AB Our aim was to characterize pelvic floor symptoms in postmenopausal women who had undergone osteoporosis evaluation and examine their association with bone mineral density (BMD). Pelvic floor symptom questionnaires were mailed to 4,026 women. Multivariate logistic regression models controlling for age, race, body mass index (BMI), and chronic obstructive pulmonary disease (COPD) were performed comparing symptoms in women with osteoporosis (T score a parts per thousand currency sign -2.5) and osteopenia (T score > -2.5 to < -1) at any site to women with normal BMD (T score: a parts per thousand yen -1, referent). There were 1,774/4,026 (44 %) questionnaires returned; 1,655 were included in the analysis (362 osteoporosis, 870 osteopenia, 423 normal BMD). Overall prevalence of any urinary incontinence (UI) was 1,226/1,640 (75 %), with UI a parts per thousand yen2-3 times/week in 699/1,197 (58 %), fecal incontinence over the past month in 247/1,549 (16 %), and prolapse in 162/1,582 (10 %). Multivariate analyses revealed that women with osteopenia had increased risk of incontinence of solid stool [adjusted odds ratio (aOR) 1.7, 95 % confidence interval (CI) 1.1-2.4). Risk of UI a parts per thousand yen2-3 times/week was not increased in women with osteoporosis (aOR 0.9, CI 0.6-1.3) and was lower in women with osteopenia (aOR 0.7, CI 0.5-0.9). In women with osteoporosis, the odds of moderate- to large-volume urine loss versus small/none was higher for those in the lower T-score quartile (lower BMD; aOR 1.43, CI 1.1-1.9). In women undergoing osteoporosis evaluation, those with osteopenia were at increased risk of fecal incontinence but not UI compared with normal women. Osteoporotic women with the lowest T scores had higher risk of moderate- to large-volume UI. It is unclear whether there is a pathophysiologic link between BMD loss and development of pelvic floor symptoms. C1 [Richter, Holly E.; Morgan, Sarah L.; Gleason, Jonathan L.; Szychowski, Jeff M.; Goode, Patricia S.; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL 35233 USA. [Goode, Patricia S.; Burgio, Kathryn L.] Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Richter, HE (reprint author), Univ Alabama Birmingham, 1700 6th Av South,Suite 10382, Birmingham, AL 35233 USA. EM hrichter@uabmc.edu FU HER-Astellas Consultant, Pelvalon [COI]; SLM-ISCD Board [COI]; JLG; PSG-Pfizer [COI]; KLB-Pfizer Consultant [COI]; University of Alabama at Birmingham, Protective Life Clinical Initiatives (PLCI) Award Program; National Institutes of Diabetes and Digestive and Kidney Diseases [2K24-DK068389] FX HER-Astellas Consultant, Pelvalon research funding, no COI; SLM-ISCD Board and Amgen Consultant, no COI; JLG-no disclosures or COI; JMS-no disclosures or COI; PSG-Pfizer research funding, no COI; KLB-Pfizer Consultant, no COI. Funding sources wer the University of Alabama at Birmingham, Protective Life Clinical Initiatives (PLCI) Award Program; partially supported by the National Institutes of Diabetes and Digestive and Kidney Diseases, 2K24-DK068389 to HER NR 27 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD OCT PY 2013 VL 24 IS 10 BP 1663 EP 1669 DI 10.1007/s00192-013-2056-4 PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 221HD UT WOS:000324647700011 PM 23389642 ER PT J AU Dvorak, CC Cowan, MJ Logan, BR Notarangelo, LD Griffith, LM Puck, JM Kohn, DB Shearer, WT O'Reilly, RJ Fleisher, TA Pai, SY Hanson, IC Pulsipher, MA Fuleihan, R Filipovich, A Goldman, F Kapoor, N Small, T Smith, A Chan, KW Cuvelier, G Heimall, J Knutsen, A Loechelt, B Moore, T Buckley, RH AF Dvorak, Christopher C. Cowan, Morton J. Logan, Brent R. Notarangelo, Luigi D. Griffith, Linda M. Puck, Jennifer M. Kohn, Donald B. Shearer, William T. O'Reilly, Richard J. Fleisher, Thomas A. Pai, Sung-Yun Hanson, I. Celine Pulsipher, Michael A. Fuleihan, Ramsay Filipovich, Alexandra Goldman, Frederick Kapoor, Neena Small, Trudy Smith, Angela Chan, Ka-Wah Cuvelier, Geoff Heimall, Jennifer Knutsen, Alan Loechelt, Brett Moore, Theodore Buckley, Rebecca H. TI The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901 SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Severe combined immunodeficiency; hematopoietic cell transplantation; newborn screening ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; THYMIC OUTPUT; SINGLE-CENTER; RECONSTITUTION; SURVIVAL; DISEASE AB The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = < 0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = < 0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes. C1 [Dvorak, Christopher C.; Cowan, Morton J.; Puck, Jennifer M.] Univ Calif San Francisco, Div Pediat Allergy Immunol & Bone Marrow Transpla, Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MA USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA USA. [Kohn, Donald B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Shearer, William T.; Hanson, I. Celine] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Shearer, William T.; Hanson, I. Celine] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [O'Reilly, Richard J.; Small, Trudy] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Fleisher, Thomas A.] NIH, Dept Lab Med, Bethesda, MA USA. [Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Div Hematol & Hematol Malignancies, Primary Childrens Med Ctr,Huntsman Canc Inst, Salt Lake City, UT USA. [Fuleihan, Ramsay] Northwestern Univ, Div Allergy & Immunol, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Chicago, IL 60611 USA. [Filipovich, Alexandra] Cincinnati Childrens Hosp, Div Hematol Oncolog, Cincinnati, OH USA. [Goldman, Frederick] Univ Alabama, Div Hematol & Oncol, Childrens Hosp Alabama, Tuscaloosa, AL USA. [Kapoor, Neena] Childrens Hosp Los Angeles, Div Res Immunol & Bone Marrow Transplantat, Los Angeles, CA 90027 USA. [Smith, Angela] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA. [Chan, Ka-Wah] Texas Transplant Inst, Pediat Stem Cell Transplantat Program, San Antonio, TX USA. [Cuvelier, Geoff] Univ Manitoba, Dept Pediat & Child Hlth, Manitoba Blood & Marrow Transplant Program, CancerCare Manitoba, Winnipeg, MB R3T 2N2, Canada. [Heimall, Jennifer] Childrens Hosp Philadelphia, Div Allergy Immunol, Philadelphia, PA 19104 USA. [Knutsen, Alan] St Louis Univ, Div Pediat Allergy & Immunol, St Louis, MO 63103 USA. [Loechelt, Brett] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Moore, Theodore] Univ Calif Los Angeles, Div Pediat Hematol Oncol, Los Angeles, CA USA. [Buckley, Rebecca H.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Buckley, Rebecca H.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. RP Dvorak, CC (reprint author), Univ Calif San Francisco, Div Pediat Allergy Immunol & Bone Marrow Transpla, Benioff Childrens Hosp, 505 Parnassus Ave,M-659, San Francisco, CA 94143 USA. EM dvorakc@peds.ucsf.edu; mcowan@peds.ucsf.edu; blogan@mcw.edu; Luigi.Notarangelo@childrens.harvard.edu; LGriffith@niaid.nih.gov; PuckJ@peds.ucsf.edu; DKohn@mednet.ucla.edu; wtsheare@texaschildrens.org; oreillyr@mskcc.org; tfleishe@cc.nih.gov; Sung-Yun.Pai@childrens.harvard.edu; ichanson@texaschildrens.org; michael.pulsipher@hsc.utah.edu; r-fuleihan@northwestern.edu; Lisa.Filipovich@cchmc.org; fgoldman@peds.uab.edu; nkapoor@chla.usc.edu; smallt@mskcc.org; smith719@umn.edu; kawah.chan@mhshealth.com; Geoff.Cuvelier@cancercare.mb.ca; heimallj@email.chop.edu; knutsenm@slu.edu; bloechel@childrensnational.org; tbmoore@mednet.ucla.edu; buckl003@mc.duke.edu RI Notarangelo, Luigi/F-9718-2016; Kohn, Donald/N-5085-2016 OI Notarangelo, Luigi/0000-0002-8335-0262; Kohn, Donald/0000-0003-1840-6087 FU National Institute of Allergy and Infectious Diseases [1U54AI082973]; NIH Office of Rare Diseases Research; National Center for Advancing Translational Science FX This paper is dedicated to the memory of Dr. Trudy Small, a gifted physician who dedicated her life to improving transplant outcomes for children with immunodeficiencies. The authors thank Elizabeth Dunn and Jessica Carlson for their tireless efforts organizing the PIDTC, Yanning Wang for expert technical assistance from the UCSF core lab, and Mary Eapen, MD and Qun Xiang from the CIBMTR for assistance with data analysis. Data collection for this study were in-part facilitated through the CIBMTR (U24-CA76518; PI Horowitz MM). The PIDTC is a part of NIH Rare Diseases Clinical Research Network, with the DMCC at the University of South Florida. Portions of this data were presented as an oral abstract at the annual meeting of the American Society for Blood and Marrow Transplant, Salt Lake City, UT, 14 February 2013 (abstract no. 93). Funding and/or programmatic support for this project has been provided by Grant #1U54AI082973 from National Institute of Allergy and Infectious Diseases and the NIH Office of Rare Diseases Research, National Center for Advancing Translational Science. The views expressed are those of the authors and do not represent the position of the NIAID, ORDR/NCATS, NIH, or the US Government. NR 31 TC 31 Z9 32 U1 1 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD OCT PY 2013 VL 33 IS 7 BP 1156 EP 1164 DI 10.1007/s10875-013-9917-y PG 9 WC Immunology SC Immunology GA 223PM UT WOS:000324818600004 PM 23818196 ER PT J AU Steidtmann, D Manber, R Blasey, C Markowitz, JC Klein, DN Rothbaum, BO Thase, ME Kocsis, JH Arnow, BA AF Steidtmann, Dana Manber, Rachel Blasey, Christine Markowitz, John C. Klein, Daniel N. Rothbaum, Barbara O. Thase, Michael E. Kocsis, James H. Arnow, Bruce A. TI Detecting Critical Decision Points in Psychotherapy and Psychotherapy plus Medication for Chronic Depression SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE chronic depression; psychotherapy for depression; psychotherapy nonremission; adaptive designs; receiver operating curve ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; ADAPTIVE TREATMENT STRATEGY; PSYCHOMETRIC PROPERTIES; ALGORITHM PROJECT; TREATMENT FAILURE; FEEDBACK; ANTIDEPRESSANTS; DISORDER; OUTCOMES AB Objective: We sought to quantify clinical decision points for identifying depression treatment nonremitters prior to end-of-treatment. Method: Data came from the psychotherapy arms of a randomized clinical trial for chronic depression. Participants (n = 352; 65.6% female; 92.3% White; mean age = 44.3 years) received 12 weeks of cognitive behavioral analysis system of psychotherapy (CBASP) or CBASP plus an antidepressant medication. In half of the sample, receiver operating curve analyses were used to identify efficient percentage of symptom reduction cut points on the Inventory of Depressive Symptoms-Self-Report (IDS-SR) for predicting end-of-treatment nonremission based on the Hamilton Rating Scale for Depression (HRSD). Sensitivity, specificity, predictive values, and Cohen's kappa for identified cut points were calculated using the remaining half of the sample. Results: Percentage of IDS-SR symptom reduction at Weeks 6 and 8 predicted end-of-treatment HRSD remission status in both the combined treatment (Week 6 cut point = 50.0%, Cohen's kappa = .42; Week 8 cut point = 54.3%, Cohen's kappa = .45) and psychotherapy only (Week 6 cut point = 60.7%, Cohen's kappa = .41; Week 8 cut point = 48.7%, Cohen's kappa = .49). Status at Week 8 was more reliable for identifying nonremitters in psychotherapy-only treatment. Conclusions: Those with chronic depression who will not remit in structured, time-limited psychotherapy for depression, either with therapy alone or in combination with antidepressant medication, are identifiable prior to end of treatment. Findings provide an operationalized strategy for designing adaptive psychotherapy interventions. C1 [Steidtmann, Dana; Manber, Rachel; Blasey, Christine; Arnow, Bruce A.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Markowitz, John C.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Markowitz, John C.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Klein, Daniel N.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA. [Rothbaum, Barbara O.] Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kocsis, James H.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. RP Steidtmann, D (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, 401 Quarry Rd, Stanford, CA 94305 USA. EM dsteidt@stanford.edu FU NIMH NIH HHS [T32 MH019938] NR 44 TC 9 Z9 9 U1 1 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2013 VL 81 IS 5 BP 783 EP 792 DI 10.1037/a0033250 PG 10 WC Psychology, Clinical SC Psychology GA 223CE UT WOS:000324780500004 PM 23750462 ER PT J AU Brief, DJ Rubin, A Keane, TM Enggasser, JL Roy, M Helmuth, E Hermos, J Lachowicz, M Rybin, D Rosenbloom, D AF Brief, Deborah J. Rubin, Amy Keane, Terence M. Enggasser, Justin L. Roy, Monica Helmuth, Eric Hermos, John Lachowicz, Mark Rybin, Denis Rosenbloom, David TI Web Intervention for OEF/OIF Veterans With Problem Drinking and PTSD Symptoms: A Randomized Clinical Trial SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE veterans; alcohol abuse; PTSD; web; Internet ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; ALCOHOL-USE DISORDERS; METHODOLOGICAL ANALYSIS; PSYCHIATRIC-DISORDERS; IDENTIFICATION TEST; SELF-HELP; IRAQ; CARE; AFGHANISTAN AB Objective: Veterans who served in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) commonly experience alcohol misuse and symptoms of posttraumatic stress disorder (PTSD) following their return from deployment to a war zone. We conducted a randomized clinical trial to evaluate the efficacy of a newly developed, 8-module, self-management web intervention (VetChange) based on motivational and cognitive-behavioral principles to reduce alcohol consumption, alcohol-related problems, and PTSD symptoms in returning combat veterans. Method: Six hundred participants, recruited through targeted Facebook ads, were randomized to either an Initial Intervention Group (IIG; n = 404) or a Delayed Intervention Group (DIG; n = 196) that waited 8 weeks for access to VetChange. Primary outcome measures were Drinks per Drinking Day, Average Weekly Drinks, Percent Heavy Drinking Days, and PTSD symptoms. Intent-to-treat analyses compared changes in outcome measures over time between IIG and DIG as well as within-group changes. Results: IIG participants demonstrated greater reductions in drinking (p < .001 for each measure) and PTSD symptoms (p = .009) between baseline and end-of-intervention than did DIG participants between baseline and the end of the waiting period. DIG participants showed similar improvements to those in IIG following participation in VetChange. Alcohol problems were also reduced within each group between baseline and 3-month follow-up. Conclusions: Results indicate that VetChange is effective in reducing drinking and PTSD symptoms in OIF/OEF veterans. Further studies of VetChange are needed to assess web-based recruitment and retention methods and to determine VetChange's effectiveness in demographic and clinical sub-populations of returning veterans. C1 [Brief, Deborah J.; Rubin, Amy; Keane, Terence M.; Helmuth, Eric; Lachowicz, Mark; Rosenbloom, David] Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Brief, Deborah J.; Rubin, Amy; Keane, Terence M.; Enggasser, Justin L.; Roy, Monica; Hermos, John; Lachowicz, Mark] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Brief, Deborah J.; Keane, Terence M.; Enggasser, Justin L.; Roy, Monica; Lachowicz, Mark] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [Rubin, Amy; Hermos, John] Boston Univ, Dept Med, Sch Med, Boston, MA 02215 USA. [Helmuth, Eric; Rosenbloom, David] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02215 USA. [Rybin, Denis] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. RP Keane, TM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 151, Boston, MA 02130 USA. EM Terry.Keane@va.gov OI Rybin, Denis/0000-0002-3657-4829 FU NIAAA NIH HHS [RC1 AA019248] NR 68 TC 19 Z9 19 U1 4 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2013 VL 81 IS 5 BP 890 EP 900 DI 10.1037/a0033697 PG 11 WC Psychology, Clinical SC Psychology GA 223CE UT WOS:000324780500015 PM 23875821 ER PT J AU Karlin, BE Trockel, M Taylor, CB Gimeno, J Manber, R AF Karlin, Bradley E. Trockel, Mickey Taylor, C. Barr Gimeno, Julia Manber, Rachel TI National Dissemination of Cognitive Behavioral Therapy for Insomnia in Veterans: Therapist- and Patient-Level Outcomes SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE cognitive-behavioral therapy; insomnia; dissemination; training; US Department of Veterans Affairs ID RANDOMIZED CONTROLLED-TRIAL; PSYCHOLOGICAL TREATMENTS; PERSISTENT INSOMNIA; METAANALYSIS; SLEEP; PHARMACOTHERAPY; DEPRESSION; EFFICACY; DISORDER AB Objective: To evaluate the effects of national training in and implementation of Cognitive Behavioral Therapy for Insomnia (CBT-I) in the U.S. Department of Veterans Affairs (VA) health care system on clinicians' competency and patients' insomnia severity, symptoms of depression, and quality of life. Method: A prospective cohort of 102 VA clinicians (including mental health staff in various mental health and primary care settings) participated in the VA CBT-I Training Program during 2011 and 2012. Patients included 182 veterans treated by clinicians enrolled in the training. Clinicians were rated on taped therapy sessions, using a standardized competency rating form. Patients' symptoms were assessed using the Insomnia Severity Index (ISI) and standardized measures of depression and quality of life. Results: Of 102 clinicians attending workshop training, 94 (92%) met all training requirements, including minimum competency score criteria. Of 182 patients, 122 (67%) completed treatment. The mixed effects model revealed significant reductions in average patient ISI score (from 19.9 to 10.2, standard error = 3.0). Patients also improved on measures of depression and quality of life. Conclusion: National training in and implementation of CBT-I resulted in a significant increase in therapist competency to deliver CBT-I for almost all clinicians and in a large reduction in insomnia severity and improvement in depression and quality of life among veterans. Observed effect sizes are comparable to results of randomized clinical trials. These results suggest CBT-I can be feasibly and effectively disseminated to routine clinical settings, with very favorable patient outcomes. C1 [Karlin, Bradley E.] US Dept Vet Affairs, Cent Off, Mental Hlth Serv, Washington, DC 20420 USA. [Karlin, Bradley E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21218 USA. [Trockel, Mickey; Taylor, C. Barr; Gimeno, Julia; Manber, Rachel] Stanford Univ, Med Ctr, Dept Psychiat, Stanford, CA 94305 USA. [Trockel, Mickey; Taylor, C. Barr; Gimeno, Julia; Manber, Rachel] Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Dept Psychiat, Palo Alto, CA USA. RP Karlin, BE (reprint author), US Dept Vet Affairs, Cent Off, Mental Hlth Serv 10P4M, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Bradley.Karlin2@va.gov NR 21 TC 29 Z9 29 U1 0 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2013 VL 81 IS 5 BP 912 EP 917 DI 10.1037/a0032554 PG 6 WC Psychology, Clinical SC Psychology GA 223CE UT WOS:000324780500017 PM 23586730 ER PT J AU Wang, ML AF Wang, Marvin L. TI UNICYCLE INJURIES IN THE UNITED STATES SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE unicycle; bicycle; injury ID BICYCLE-RELATED INJURIES; EMERGENCY-DEPARTMENTS; CHILDREN; POPULATION AB Background: Unicycles are single-wheel machines ridden for transportation or recreation. To our knowledge, no studies have been performed that describe injury rates of unicycle use. Objective: The objective of this study was to describe the epidemiological characteristics of unicycle injuries treated in United States (US) emergency departments (EDs). Methods: A retrospective analysis was performed using data from the National Electronic Injury Surveillance System (NEISS) of the US Consumer Product Safety Commission from 1991 through 2010. Results: An estimated 3360 patients were treated for unicycle injuries from 1991 to 2010, averaging 168 injuries per year in the United States. Ten to fourteen-year-old patients represented 41% of the entire study cohort. Fractures represented approximately one third (32.9%) of all injuries treated. More than half (52.9%) of all injuries involved an extremity. Six of the 85 cases studied involved a head injury; all were aged younger than 18 years. Only 3.53% of all studied cases were admitted for further treatment. The rest were treated in the ED and discharged to home. Fractures were the primary diagnosis in all admitted cases. Conclusions: Based on NEISS data, unicycle injuries treated in EDs are relatively uncommon and rarely require admission. Of documented injuries, fractures and extremity injuries are most common. Additional research is needed to understand the underlying mechanisms of these injuries as well as the potential need for helmet use advocacy. (C) 2013 Elsevier Inc. C1 [Wang, Marvin L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Marvin L.] Harvard Univ, Sch Med, Boston, MA USA. RP Wang, ML (reprint author), Founders 526, Boston, MA 02114 USA. NR 23 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2013 VL 45 IS 4 BP 502 EP 507 DI 10.1016/j.jemermed.2013.05.024 PG 6 WC Emergency Medicine SC Emergency Medicine GA 224CO UT WOS:000324859400014 PM 23871477 ER PT J AU Laney, DA Bennett, RL Clarke, V Fox, A Hopkin, RJ Johnson, J O'Rourke, E Sims, K Walter, G AF Laney, Dawn A. Bennett, Robin L. Clarke, Virginia Fox, Angela Hopkin, Robert J. Johnson, Jack O'Rourke, Erin Sims, Katherine Walter, Gerald TI Fabry Disease Practice Guidelines: Recommendations of the National Society of Genetic Counselors SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE Fabry disease; Enzyme replacement therapy; Genetic counseling; Newborn screening; Lysosomal storage diseases ID ENZYME REPLACEMENT THERAPY; QUALITY-OF-LIFE; ANGIOKERATOMA CORPORIS DIFFUSUM; ALPHA-GALACTOSIDASE; CLINICAL-MANIFESTATIONS; AGALSIDASE-BETA; STORAGE; REGISTRY; FEMALES; TRIAL AB Identification and comprehensive care of individuals who have Fabry disease (FD) requires a multidisciplinary approach inclusive of genetic testing, test interpretation, genetic counseling, long term disease symptom monitoring, treatment recommendations, and coordination of therapy. The purpose of this document is to provide health care professionals with guidelines for testing, care coordination, identification of psychosocial issues, and to facilitate a better understanding of disease treatment expert recommendations for patients with Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as representatives/founders of the two United States based Fabry disease patient advocacy groups who are themselves affected by Fabry disease. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing, interpretation of results, psychosocial considerations, and references to professional and patient resources. C1 [Laney, Dawn A.] Emory Univ, Decatur, GA 30033 USA. [Bennett, Robin L.] Univ Washington, Med Ctr Med Genet, Seattle, WA 98195 USA. [Clarke, Virginia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Angela] Sera Prognost, Salt Lake City, UT 84109 USA. [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Johnson, Jack] Fabry Support & Informat Grp, Concordia, MO 64020 USA. [O'Rourke, Erin] Genzyme Corp, Genzyme, Cambridge, MA 02142 USA. [Sims, Katherine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walter, Gerald] Natl Fabry Dis Fdn, Washington, DC 20008 USA. RP Laney, DA (reprint author), Emory Univ, 2165 North Decatur Rd, Decatur, GA 30033 USA. EM dawn.laney@emory.edu; robinb@uw.edu; vclarke1@partners.org; ang_fox@hotmail.com; rob.hopkin@cchmc.org; jjohnson@fabry.org; Erin.ORourke@genzyme.com; ksims@partners.org; jerry.walter@fabrydisease.org OI Hopkin, Robert/0000-0003-0770-5516 NR 71 TC 11 Z9 13 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 EI 1573-3599 J9 J GENET COUNS JI J. Genet. Couns. PD OCT PY 2013 VL 22 IS 5 BP 555 EP 564 DI 10.1007/s10897-013-9613-3 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 219HG UT WOS:000324496300001 PM 23860966 ER PT J AU Lunze, FI Colan, SD Gauvreau, K Perez-Atayde, AR Smith, RN Blume, ED Singh, TP AF Lunze, Fatima I. Colan, Steven D. Gauvreau, Kimberlee Perez-Atayde, Antonio R. Smith, Rex N. Blume, Elizabeth D. Singh, Tajinder P. TI Tissue Doppler imaging for rejection surveillance in pediatric heart transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE heart transplant; children; cardiac biopsy; rejection surveillance; tissue Doppler imaging ID ENDOMYOCARDIAL BIOPSY; ALLOGRAFT-REJECTION; MYOCARDIAL VELOCITIES; NONINVASIVE DETECTION; CHILDREN; ECHOCARDIOGRAPHY AB BACKGROUND: Most transplant centers perform serial cardiac biopsies for rejection surveillance in pediatric heart transplant (HT) recipients. We sought to assess tissue Doppler imaging (TDI) findings during biopsy specimen-proven rejection in pediatric HT recipients and to develop TDI criteria for absence of rejection with high predictive accuracy. METHODS: We included the 122 HT recipients in follow-up at our center (median age at HT, 8.7 years). We identified all echocardiograms with adequate TDI data performed within 24 hours of a cardiac biopsy during 2005 to 2011. Rejection was defined as Grade >= 2R cellular rejection or antibody-mediated rejection. Paired comparisons of TDI velocities were made using patients' baseline velocities as the control. RESULTS: Overall, 647 specimen-pairs were identified where there was no rejection at baseline. In 24 of these, the second biopsy specimen demonstrated rejection. Using receiver operating characteristic curve analysis of percentage change from baseline, we identified < 15% decline in left ventricular (LV) S' velocity and < 5% decline in LV A' velocity to individually predict non-rejection with > 99% accuracy. When joint criteria were used, the predictive accuracy was 100%, and no rejection event was misclassified. More than 75% of TDI pairs met these criteria for non-rejection. CONCLUSIONS: Biopsy specimen-proven rejection is associated with a significant decline in biventricular TDI velocities from baseline in pediatric HT recipients. By using well-defined TDI criteria to predict non-rejection, a substantial proportion of planned biopsies may be deferred or avoided at minimal risk to pediatric HT recipients. Published by Elsevier Inc. C1 [Lunze, Fatima I.; Colan, Steven D.; Gauvreau, Kimberlee; Blume, Elizabeth D.; Singh, Tajinder P.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Colan, Steven D.; Blume, Elizabeth D.; Singh, Tajinder P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Gauvreau, Kimberlee] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.; Smith, Rex N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Smith, Rex N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lunze, FI (reprint author), Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM fatima.lunze@cardio.chboston.org OI Lunze, Fatima/0000-0002-7888-1480 FU German Research Council (Deutsche Forschungsgemeinschaft, Germany) [1587/1-1]; Heart Transplant Research and Education Fund, Boston Children's Hospital FX Dr. Lunze was funded by the German Research Council (Deutsche Forschungsgemeinschaft, Germany, 1587/1-1). This study was supported by the Heart Transplant Research and Education Fund, Boston Children's Hospital. NR 26 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD OCT PY 2013 VL 32 IS 10 BP 1027 EP 1033 DI 10.1016/j.healun.2013.06.016 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 226OB UT WOS:000325044600012 PM 23937884 ER PT J AU Meulenbroek, LAPM de Jong, RJ Jager, CFD Monsuur, HN Wouters, D Nauta, AJ Knippels, LMJ van Neerven, RJJ Ruiter, B Leusen, JHW Hack, CE Bruijnzeel-Koomen, CAFM Knulst, AC Garssen, J van Hoffen, E AF Meulenbroek, Laura A. P. M. de Jong, Renske J. Jager, Constance F. den Hartog Monsuur, Hanneke N. Wouters, Diana Nauta, Alma J. Knippels, Leon M. J. van Neerven, R. J. Joost Ruiter, Bert Leusen, Jeanette H. W. Hack, C. Erik Bruijnzeel-Koomen, Carla A. F. M. Knulst, Andre C. Garssen, Johan van Hoffen, Els TI IgG Antibodies in Food Allergy Influence Allergen-Antibody Complex Formation and Binding to B Cells: A Role for Complement Receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-RESPONSES; ANTIGEN PRESENTATION; BLOCKING ANTIBODIES; NATURAL ANTIBODY; PEANUT ALLERGY; DOUBLE-BLIND; FC REGIONS; T-CELLS; ACTIVATION; INHIBITION AB Allergen-IgE complexes are more efficiently internalized and presented by B cells than allergens alone. It has been suggested that IgG Abs induced by immunotherapy inhibit these processes. Food-allergic patients have high allergen-specific IgG levels. However, the role of these Abs in complex formation and binding to B cells is unknown. To investigate this, we incubated sera of peanut-or cow's milk-allergic patients with their major allergens to form complexes and added them to EBV-transformed or peripheral blood B cells (PBBCs). Samples of birch pollen-allergic patients were used as control. Complex binding to B cells in presence or absence of blocking Abs to CD23, CD32, complement receptor 1 (CR1, CD35), and/or CR2 (CD21) was determined by flow cytometry. Furthermore, intact and IgG-depleted sera were compared. These experiments showed that allergen-Ab complexes formed in birch pollen, as well as food allergy, contained IgE, IgG1, and IgG4 Abs and bound to B cells. Binding of these complexes to EBV-transformed B cells was completely mediated by CD23, whereas binding to PBBCs was dependent on both CD23 and CR2. This reflected differential receptor expression. Upon IgG depletion, allergen-Ab complexes bound to PBBCs exclusively via CD23. These data indicated that IgG Abs are involved in complex formation. The presence of IgG in allergen-IgE complexes results in binding to B cells via CR2 in addition to CD23. The binding to both CR2 and CD23 may affect Ag processing and presentation, and (may) thereby influence the allergic response. C1 [Meulenbroek, Laura A. P. M.; de Jong, Renske J.; Jager, Constance F. den Hartog; Monsuur, Hanneke N.; Hack, C. Erik; Bruijnzeel-Koomen, Carla A. F. M.; Knulst, Andre C.; van Hoffen, Els] Univ Med Ctr Utrecht, Dept Dermatol & Allergol, NL-3508 GA Utrecht, Netherlands. [Meulenbroek, Laura A. P. M.; Nauta, Alma J.; Knippels, Leon M. J.; Garssen, Johan] Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacol, NL-3508 TB Utrecht, Netherlands. [Wouters, Diana] Sanquin Res, Dept Immunopathol, NL-1006 AN Amsterdam, Netherlands. [Nauta, Alma J.] Danone Res Ctr Specialised Nutr, Dept Immunol, Singapore 138667, Singapore. [Knippels, Leon M. J.; Garssen, Johan] Danone Res Ctr Specialised Nutr, Dept Immunol, NL-6700 CA Wageningen, Netherlands. [van Neerven, R. J. Joost] FrieslandCampina Res, NL-3800 BN Amersfoort, Netherlands. [van Neerven, R. J. Joost] Wageningen Univ, Cell Biol & Immunol Grp, NL-6708 WD Wageningen, Netherlands. [Ruiter, Bert] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. [Leusen, Jeanette H. W.; Hack, C. Erik] Univ Med Ctr Utrecht, Lab Translat Immunol, NL-3508 AB Utrecht, Netherlands. RP Meulenbroek, LAPM (reprint author), Univ Med Ctr Utrecht, Lab Translat Immunol KC 02 085 2, POB 85090, NL-3508 AB Utrecht, Netherlands. EM laurameulenbroek@home.nl RI Leusen, Jeanette/I-9010-2014; garssen, johan/I-7159-2016; OI Leusen, Jeanette/0000-0003-4982-6914 FU Danone Research Centre for Specialised Nutrition; HAL Allergy; Top Institute Pharma; Carbohydrate Competence Center FX This work was supported in part by the Danone Research Centre for Specialised Nutrition (to L. A. P. M. M. and E. v. H.). E. v. H. received research support for investigator-driven research for peanut allergy from HAL Allergy. L.M.J.K. and J.G. received government grants from Top Institute Pharma and the Carbohydrate Competence Center. NR 41 TC 8 Z9 8 U1 0 U2 19 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2013 VL 191 IS 7 BP 3526 EP 3533 DI 10.4049/jimmunol.1202398 PG 8 WC Immunology SC Immunology GA 221CH UT WOS:000324634500008 PM 23997216 ER PT J AU Lina, TT Pinchuk, IV House, J Yamaoka, Y Graham, DY Beswick, EJ Reyes, VE AF Lina, Taslima T. Pinchuk, Irina V. House, Jennifer Yamaoka, Yoshio Graham, David Y. Beswick, Ellen J. Reyes, Victor E. TI CagA-Dependent Downregulation of B7-H2 Expression on Gastric Mucosa and Inhibition of Th17 Responses during Helicobacter pylori Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCIBLE COSTIMULATOR LIGAND; T-CELL RESPONSE; EPITHELIAL-CELLS; POTENTIAL ROLE; IV SECRETION; MICE; PATHOGENESIS; ACTIVATION; PROTEIN; INTERLEUKIN-8 AB Gastric epithelial cells (GECs) are the primary target for Helicobacter pylori infection and may act as APCs regulating local T cell responses. We previously reported that H. pylori infection of GECs induces the expression of the T cell coinhibitory molecule B7-H1 on GECs. This process contributes to the hyporesponsiveness of CD4(+) effector T cells and accumulation of regulatory T cells. In the present study, we investigated the impact of H. pylori cytotoxin-associated gene A (CagA) on the modulation of the expression of the T cell costimulator B7-H2 by GECs. B7-H2 is involved in promoting Th17 type responses. H. pylori infection downregulates B7-H2 expression by GECs in a CagA-dependent manner. IFN-gamma, which is increased in the H. pylori-infected gastric mucosa, synergizes with H. pylori in downregulating B7-H2 expression by GECs. CagA-mediated modulation of B7-H2 on GECs involves p70 S6 kinase phosphorylation. The CagA-dependent B7-H2 downregulation in GECs correlates with a decrease in Th17 type responses in vitro and in vivo. Furthermore, CagA-dependent modulation of Th17 responses was inversely correlated with the H. pylori colonization levels in vivo. Our data suggest that CagA contributes to the ability of H. pylori to evade Th17-mediated clearance by modulating expression of B7-H2 and, thus, to the establishment of the H. pylori chronic infection. C1 [Lina, Taslima T.; Pinchuk, Irina V.; Reyes, Victor E.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Pinchuk, Irina V.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA. [House, Jennifer; Reyes, Victor E.] Univ Texas Med Branch, Dept Pediat, Galveston, TX 77555 USA. [Yamaoka, Yoshio; Graham, David Y.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Beswick, Ellen J.] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. RP Reyes, VE (reprint author), Univ Texas Med Branch, Childrens Hosp, Dept Pediat, 301 Univ Blvd, Galveston, TX 77555 USA. EM vreyes@utmb.edu RI Pinchuk, Irina/A-7227-2008 OI Pinchuk, Irina/0000-0003-1505-5779 FU National Institutes of Health [AI68712, DK090090-01, CA127022, 1U54RR02614, 8UL1TR000041]; American Gastroenterological Association; University of Texas Medical Branch; University of Texas Medical Branch Sealy Center for Vaccine Development; American Cancer Society [RSG-10-159-01-LIB]; University of New Mexico Clinical and Translational Science Center FX This work was supported by National Institutes of Health Grants AI68712, DK090090-01, and CA127022; the American Gastroenterological Association Research Scholar Award; National Institutes of Health Grant 1U54RR02614; the University of Texas Medical Branch Clinical and Translational Sciences Award; a University of Texas Medical Branch Sealy Center for Vaccine Development predoctoral fellowship (to T.T.L.); American Cancer Society Grant RSG-10-159-01-LIB; National Institutes of Health Grant 8UL1TR000041; and by the University of New Mexico Clinical and Translational Science Center. NR 60 TC 10 Z9 11 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2013 VL 191 IS 7 BP 3838 EP 3846 DI 10.4049/jimmunol.1300524 PG 9 WC Immunology SC Immunology GA 221CH UT WOS:000324634500039 PM 23997227 ER PT J AU Chemali, J Ching, SN Purdon, PL Solt, K Brown, EN AF Chemali, Jessica Ching, ShiNung Purdon, Patrick L. Solt, Ken Brown, Emery N. TI Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID BISPECTRAL INDEX; BEHAVIORAL-EXPERIMENTS; ISOFLURANE ANESTHESIA; ELECTROENCEPHALOGRAM; EMERGENCE; PHYSOSTIGMINE; HYPOTHERMIA; PATTERNS; MODEL; RATS AB Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit. C1 [Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Chemali, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM enb@neurostat.mit.edu OI Solt, Ken/0000-0001-5328-2062 FU NIH [DP1-OD003646, DP2-OD006454, K08-GM094394]; Burroughs-Wellcome Fund [1010625] FX This work was supported by: NIH Awards DP1-OD003646 (ENB), DP2-OD006454 (PP), K08-GM094394 (KS), and the Burroughs-Wellcome Fund Award 1010625 (SC). NR 45 TC 12 Z9 12 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD OCT PY 2013 VL 10 IS 5 AR 056017 DI 10.1088/1741-2560/10/5/056017 PG 12 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 224DN UT WOS:000324862400017 PM 24018288 ER PT J AU Wu, F Stark, E Im, M Cho, IJ Yoon, ES Buzsaki, G Wise, KD Yoon, E AF Wu, Fan Stark, Eran Im, Maesoon Cho, Il-Joo Yoon, Eui-Sung Buzsaki, Gyoergy Wise, Kensall D. Yoon, Euisik TI An implantable neural probe with monolithically integrated dielectric waveguide and recording electrodes for optogenetics applications SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID OPTICAL CONTROL; MILLISECOND-TIMESCALE; NEURONS; CHANNELRHODOPSIN-2; CIRCUITS; BRAIN; MICROSTIMULATION; STIMULATION; PERFORMANCE; INHIBITION AB Objective. Optogenetics promises exciting neuroscience research by offering optical stimulation of neurons with unprecedented temporal resolution, cell-type specificity and the ability to excite as well as to silence neurons. This work provides the technical solution to deliver light to local neurons and record neural potentials, facilitating local circuit analysis and bridging the gap between optogenetics and neurophysiology research. Approach. We have designed and obtained the first in vivo validation of a neural probe with monolithically integrated electrodes and waveguide. High spatial precision enables optical excitation of targeted neurons with minimal power and recording of single-units in dense cortical and subcortical regions. Main results. The total coupling and transmission loss through the dielectric waveguide at 473 nm was 10.5 +/- 1.9 dB, corresponding to an average output intensity of 9400 mW mm(-2) when coupled to a 7 mW optical fiber. Spontaneous field potentials and spiking activities of multiple Channelrhodopsin-2 expressing neurons were recorded in the hippocampus CA1 region of an anesthetized rat. Blue light stimulation at intensity of 51 mW mm(-2) induced robust spiking activities in the physiologically identified local populations. Significance. This minimally invasive, complete monolithic integration provides unmatched spatial precision and scalability for future optogenetics studies at deep brain regions with high neuronal density. C1 [Wu, Fan; Im, Maesoon; Cho, Il-Joo; Wise, Kensall D.; Yoon, Euisik] Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. [Stark, Eran; Buzsaki, Gyoergy] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. [Wu, Fan; Buzsaki, Gyoergy] NYU, Neurosci Inst, Alexandria Ctr, New York, NY 10016 USA. [Im, Maesoon] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Cho, Il-Joo; Yoon, Eui-Sung] Korea Inst Sci & Technol, Brain Sci Inst, Ctr BioMicrosyst, Seoul 136791, South Korea. RP Wu, F (reprint author), Univ Michigan, Dept Elect Engn & Comp Sci, 1301 Beal Ave, Ann Arbor, MI 48109 USA. EM esyoon@umich.edu OI Buzsaki, Gyorgy/0000-0002-3100-4800 FU NSF; KIST Institutional Program; [NSF-ECCS-1102067] FX This work has been funded in part by NSF with the Graduate Research Fellowship awarded to Fan Wu and NSF-ECCS-1102067, and in part by KIST Institutional Program. Fabrication of the probes has been done at the Lurie Nanofabrication Facility at the University of Michigan. NR 39 TC 45 Z9 47 U1 7 U2 34 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD OCT PY 2013 VL 10 IS 5 AR 056012 DI 10.1088/1741-2560/10/5/056012 PG 9 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 224DN UT WOS:000324862400012 PM 23985803 ER PT J AU Zhang, JP Lee, EQ Nayak, L Doherty, L Kesari, S Muzikansky, A Norden, AD Chen, HC Wen, PY Drappatz, J AF Zhang, Jun-Ping Lee, Eudocia Q. Nayak, Lakshmi Doherty, Lisa Kesari, Santosh Muzikansky, Alona Norden, Andrew D. Chen, Huichao Wen, Patrick Y. Drappatz, Jan TI Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Pemetrexed; Primary central nervous system lymphoma; Secondary central nervous system lymphoma; Salvage chemotherapy ID PRIMARY CNS LYMPHOMA; RECURRENT PRIMARY CNS; PHASE-II; TEMOZOLOMIDE; RITUXIMAB; CHEMOTHERAPY; COMBINATION; TOPOTECAN AB There is currently no standard therapy for recurrent or chemotherapy-refractory central nervous system lymphoma (CNSL). Pemetrexed has been reported to have activity in patients with primary CNSL (PCNSL). The use of pemetrexed in secondary CNS lymphoma (SCNSL) has not previously been reported. Here we retrospectively review the outcomes and toxicities of standard and modified doses of pemetrexed as salvage therapy in 18 PCNSL and 12 SCNSL patients. The overall response rate for PCNSL patients was 64.7 %, all of whom achieved a complete response (CR). The median progression-free survival (PFS) was 5.8 months. For the SCNSL patients, RR was 58.3 % with 2 CR (16.7 %); the median PFS was 2.5 months. Grade a parts per thousand yen3 adverse events included leukopenia in 5 patients (16.7 %), neutropenia in 1 patient (3.3 %), and fatigue in 3 patients (10.0 %). 3 patients died while on treatment, 2 due to infections and 1 due to pulmonary embolism. Our results indicate that pemetrexed has activity as salvage therapy in recurrent PCNSL, even with modified dosing, but outcomes trend towards less favorable in SCNSL. C1 [Zhang, Jun-Ping] Capital Med Univ, Beijing Sanbo Brain Hosp, Dept Neurooncol, Beijing, Peoples R China. [Lee, Eudocia Q.; Nayak, Lakshmi; Doherty, Lisa; Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Kesari, Santosh] Univ Calif San Diego, Ctr Translat Neurooncol, Dept Neurosci, La Jolla, CA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Chen, Huichao] Harvard Univ, Sch Publ Hlth, Dept Biostat, Bostan, MA USA. [Drappatz, Jan] Univ Pittsburgh, Med Ctr, Dept Neurol, Div Hematol & Oncol, Pittsburgh, PA 15232 USA. [Drappatz, Jan] Univ Pittsburgh, Med Ctr, Dept Med, Div Hematol & Oncol, Pittsburgh, PA 15232 USA. RP Drappatz, J (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, Div Hematol & Oncol, UPMC Canc Pavil,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM drappatzj@upmc.edu RI Kesari, Santosh/E-8461-2013 FU Society for Neuro-Oncology International Outreach Fellowship; American Brain Tumor Association; EMD Serono FX J-PZ was supported by the Society for Neuro-Oncology International Outreach Fellowship with funding from the American Brain Tumor Association and EMD Serono. NR 19 TC 3 Z9 4 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2013 VL 115 IS 1 BP 71 EP 77 DI 10.1007/s11060-013-1196-1 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 227VP UT WOS:000325143900009 PM 23828279 ER PT J AU Abramowicz, S Susarla, HK Kim, S Kaban, LB AF Abramowicz, Shelly Susarla, Harlyn K. Kim, Susan Kaban, Leonard B. TI Physical Findings Associated With Active Temporomandibular Joint Inflammation in Children With Juvenile Idiopathic Arthritis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 10-15, 2012 CL San Diego, CA SP Amer Assoc Oral & Maxillofacial Surg ID INVOLVEMENT; PREVALENCE; ULTRASOUND; SIGNS AB Purpose: To identify the physical findings associated with active temporomandibular joint (TMJ) inflammation (ie, synovitis) in children with juvenile idiopathic arthritis (JIA). Patients and Methods: This was a retrospective study of children with JIA evaluated at Boston Children's Hospital. The patients were included if they had a confirmed diagnosis of JIA and had undergone a TMJ magnetic resonance imaging (MRI) study with contrast. Medical records and imaging studies were reviewed to document the demographic, physical (ie, facial asymmetry, joint noises, maximal incisal opening, deviation on opening, occlusal cant), and MRI findings. The outcome variable was TMJ synovitis on the MRI study. Descriptive and bivariate statistics were computed. Multiple regression models were used to identify associations (P <=. 05, significance). Results: A total of 51 patients with JIA were evaluated during the study period. Of these, 43 patients (33 girls) with a mean age of 11.4 years met the inclusion criteria. MRI demonstrated TMJ synovitis in 27 patients. The age-adjusted limited maximal incisal opening (MIO) and deviation on opening were the only physical findings significantly associated with synovitis on MRI (P = .003 and P = .043, respectively). Using these parameters as predictors of synovitis, a limited MIO and deviation on opening had a high specificity (86% and 94%, respectively). Patients with a limited MIO were 6.7 times more likely to have synovitis than those with a normal MIO. All patients with a limited MIO and deviation on opening had TMJ synovitis on the MRI scan. Conclusions: The results of this study indicate that, in children with JIA, limited MIO and deviation on opening can be used to predict the presence of TMJ synovitis. Documentation of these parameters should be an essential part of the clinical examination and longitudinal follow-up of children with JIA. (C) 2013 American Association of Oral and Maxillofacial Surgeons C1 [Abramowicz, Shelly; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Abramowicz, Shelly] Boston Childrens Hosp, Boston, MA 02445 USA. [Susarla, Harlyn K.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Kim, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Susan] Boston Childrens Hosp, Rheumatol Program, Boston, MA 02445 USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Abramowicz, S (reprint author), Boston Childrens Hosp, Dept Plast & Oral Surg, 300 Longwood Ave, Boston, MA 02445 USA. EM shelly.abramowicz@childrens.harvard.edu NR 18 TC 11 Z9 11 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2013 VL 71 IS 10 BP 1683 EP 1687 DI 10.1016/j.joms.2013.04.009 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 219AS UT WOS:000324476700010 PM 23932113 ER PT J AU Hasegawa, K Tsugawa, Y Brown, DFM Camargo, CA AF Hasegawa, Kohei Tsugawa, Yusuke Brown, David F. M. Camargo, Carlos A., Jr. TI Childhood Asthma Hospitalizations in the United States, 2000-2009 SO JOURNAL OF PEDIATRICS LA English DT Article ID COMPLEX CHRONIC CONDITIONS; EMERGENCY-DEPARTMENT; CHILDREN; CARE; TRENDS; MORTALITY; QUALITY; COSTS; EXPENDITURE; PREVALENCE AB Objective To examine temporal trends in the US incidence of childhood asthma hospitalizations, in-hospital mortality, mechanical ventilation use, and hospital charges between 2000 and 2009. Study design This was a serial, cross-sectional analysis of a nationally representative sample of children hospitalized with acute asthma. The Kids Inpatient Database was used to identify children aged <18 years with asthma by International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx. Outcome measures were asthma hospitalization incidence, in-hospital mortality, mechanical ventilation use, and hospital charges. We examined temporal trends of each outcome, accounting for sampling weights. Hospital charges were adjusted for inflation to 2009 US dollars. Results The 4 separate years (2000, 2003, 2006, and 2009) of national discharge data included a total of 592 805 weighted discharges with asthma. Between 2000 and 2009, the rate of asthma hospitalization in US children decreased from 21.1 to 18.4 per 10 000 person-years (13% decrease; P-trend < .001). Mortality declined significantly after adjusting for confounders (OR for comparison of 2009 with 2000, 0.37; 95% CI, 0.17-0.79). In contrast, there was an increase in the use of mechanical ventilation (from 0.8% to 1.0%, a 28% increase; P-trend < .001). Nationwide hospital charges also increased from $1.27 billion to $1.59 billion (26% increase; P-trend < .001); this increase was driven by a rise in the geometric mean of hospital charges per discharge, from $5940 to $8410 (42% increase; P-trend <. 001). Conclusion Between 2000 and 2009, we found significant declines in asthma hospitalization and in-hospital mortality among US children. In contrast, mechanical ventilation use and hospital charges for asthma increased significantly over this same period. C1 [Hasegawa, Kohei; Brown, David F. M.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hasegawa, Kohei; Tsugawa, Yusuke; Brown, David F. M.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Tsugawa, Yusuke] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Tsugawa, Yusuke] St Lukes Life Sci Inst, Ctr Clin Epidemiol, Tokyo, Japan. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU St Luke's Life Science Institute, Tokyo, Japan; National Institutes of Health [U01 AI-87881] FX K.H. and Y.T. were supported in part by the St Luke's Life Science Institute, Tokyo, Japan. C. C. was supported by the National Institutes of Health (U01 AI-87881). C. C. has provided asthma-related consultation for Genentech, GlaxoSmithKline, Merck, Novartis, and Pfizer. The other authors declare no conflicts of interest. NR 41 TC 18 Z9 19 U1 1 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2013 VL 163 IS 4 BP 1127 EP + DI 10.1016/j.jpeds.2013.05.002 PG 10 WC Pediatrics SC Pediatrics GA 224HM UT WOS:000324873700040 PM 23769497 ER PT J AU Lafosse, JM Mitchell, SM Corboy, JR Filley, CM AF Lafosse, Jose M. Mitchell, Sandra M. Corboy, John R. Filley, Christopher M. TI The Nature of Verbal Memory Impairment in Multiple Sclerosis: A List-Learning and Meta-analytic Study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Multiple sclerosis; Memory; Learning; White matter disease; Neuropsychological tests; Meta analysis ID COGNITIVE IMPAIRMENT; WHITE-MATTER; NEUROPSYCHOLOGICAL IMPAIRMENT; WORKING-MEMORY; MS; PERFORMANCE; DEFICITS; ATROPHY; RECALL; SPEED AB The primary purpose of this study was to test the hypothesis that multiple sclerosis (MS) patients have impaired acquisition rather than a retrieval deficit. Verbal memory impairment in MS was examined in 53 relapsing-remitting MS patients and 31 healthy controls (HC), and in a meta-analysis of studies that examined memory functioning in MS with list-learning tasks. The MS group demonstrated significantly lower acquisition and delayed recall performance than the HC group, and the meta-analysis revealed that the largest effect sizes were obtained for acquisition measures relative to delayed recall and recognition. Our data argue against a retrieval deficit as the sole explanation for verbal memory impairment in MS, and make a consistent case for the position that deficient acquisition contributes to the memory dysfunction of MS patients. Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing. C1 [Lafosse, Jose M.] Regis Univ, Dept Psychol & Neurosci, Denver, CO 80221 USA. [Mitchell, Sandra M.] New Mexico Vet Affairs Healthcare Syst, Albuquerque, NM USA. [Corboy, John R.; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. [Corboy, John R.; Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. RP Lafosse, JM (reprint author), Regis Univ, Dept Psychol & Neurosci, 3333 Regis Blvd,D-12, Denver, CO 80221 USA. EM jlafosse@regis.edu FU Regis University FX None of the authors have any conflict of interest to report. This research received no specific grant from any funding agency, commercial or not-for-profit sectors, but was supported by a sabbatical leave to Dr. Lafosse from Regis University. We thank Nancy L. Leech, Ph.D. for her assistance with meta-analytic techniques, Ted Krmpotich for his assistance with data collection, and the Regis University students enrolled in Neuropsychology during spring 2013 for their helpful reviews of the manuscript. NR 100 TC 4 Z9 4 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD OCT PY 2013 VL 19 IS 9 BP 995 EP 1008 DI 10.1017/S1355617713000957 PG 14 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 223RY UT WOS:000324827700006 PM 24059259 ER PT J AU Wright, CD AF Wright, Cameron D. TI Historical perspectives of The American Association for Thoracic Surgery: W. Gerald Austen SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2013 VL 146 IS 4 BP 745 EP 747 DI 10.1016/j.jtcvs.2012.04.015 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 219CE UT WOS:000324481400013 PM 22626513 ER PT J AU Karlin, JD Koontz, BF Freedland, SJ Moul, JW Grob, BM Wan, W Hagan, MP Anscher, MS Moghanaki, D AF Karlin, Jeremy D. Koontz, Bridget F. Freedland, Stephen J. Moul, Judd W. Grob, Baruch M. Wan, Wen Hagan, Michael P. Anscher, Mitchell S. Moghanaki, Drew TI Identifying Appropriate Patients for Early Salvage Radiotherapy after Prostatectomy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; salvage therapy; radiotherapy ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; BIOCHEMICAL RECURRENCE; POSTOPERATIVE RADIOTHERAPY; ADJUVANT RADIOTHERAPY; TREATMENT FAILURE; CANCER; RISK; TRIAL; CONSENSUS AB Purpose: It remains unclear whether relapsed prostate specific antigen at postprostatectomy salvage radiotherapy impacts outcomes as long it is 1.0 ng/ml or less. Materials and Methods: We performed a retrospective cohort study of 197 patients treated with salvage radiotherapy in the setting of detectable relapsed prostate specific antigen 1.0 ng/ml or less. Patients were excluded from analysis if they had lymph node involvement or received androgen deprivation therapy. Freedom from prostate specific antigen progression after salvage radiotherapy was analyzed by a Cox regression model. Results: Median relapsed prostate specific antigen was 0.33 ng/ml (range 0.07 to 1.0). There was 86% freedom from prostate specific antigen progression at a median followup of 52 months. Relapsed prostate specific antigen (HR 1.9, p = 0.004), Gleason score 8-10 (HR 5.2, p <0.001) and negative margin status (HR 2.0, p = 0.02) were independently associated with an increased risk of prostate specific antigen progression after salvage radiotherapy. We identified interaction between relapsed prostate specific antigen and Gleason score (p = 0.04) but not margin status. A significant association was noted between higher relapsed prostate specific antigen and prostate specific antigen progression after salvage radiotherapy in patients with Gleason score 8-10 but not 7 or less. In patients with Gleason score 8-10 the rate of freedom from prostate specific antigen progression at 53 months was 77% vs 26% when salvage radiotherapy was initiated at a relapsed prostate specific antigen of 0.33 or less vs 0.34 to 1.0 ng/ml (log rank p = 0.003). Conclusions: Different relapsed prostate specific antigen thresholds for unsuccessful salvage radiotherapy may exist based on Gleason score. These data suggest that patients with Gleason score 8-10 should be offered salvage radiotherapy at the earliest detectable relapsed prostate specific antigen, even 0.33 ng/ml or less. Those with Gleason score 7 or less may have the opportunity to be followed with serial prostate specific antigen measurements to improve risk stratification, and delay and/or avoid the potential toxicity of salvage radiotherapy. C1 [Karlin, Jeremy D.; Hagan, Michael P.; Anscher, Mitchell S.; Moghanaki, Drew] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23284 USA. [Wan, Wen] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA USA. [Grob, Baruch M.] Hunter Holmes McGuire Vet Affairs Med Ctr, Urol Serv, Richmond, VA USA. [Hagan, Michael P.; Moghanaki, Drew] Hunter Holmes McGuire Vet Affairs Med Ctr, Radiat Oncol Serv, Richmond, VA USA. [Hagan, Michael P.] US Dept Vet Affairs, Natl Radiat Oncol Program, Richmond, VA USA. [Koontz, Bridget F.] Duke Univ Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Freedland, Stephen J.; Moul, Judd W.] Duke Univ Med Ctr, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.; Moul, Judd W.] Duke Univ Med Ctr, Duke Canc Inst, Durham, NC USA. [Freedland, Stephen J.] Durham Vet Affairs Med Ctr, Urol Serv, Durham, NC USA. [Freedland, Stephen J.] Duke Univ Sch Med, Dept Pathol, Durham, NC USA. RP Moghanaki, D (reprint author), Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23284 USA. OI Anscher, Mitchell/0000-0003-4480-111X NR 22 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2013 VL 190 IS 4 BP 1410 EP 1415 DI 10.1016/j.juro.2013.04.078 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 227EH UT WOS:000325091700103 PM 23648223 ER PT J AU Neal, KL Shakerdge, NB Hou, SS Klunk, WE Mathis, CA Nesterov, EE Swager, TM McLean, PJ Bacskai, BJ AF Neal, Krista L. Shakerdge, Naomi B. Hou, Steven S. Klunk, William E. Mathis, Chester A. Nesterov, Evgueni E. Swager, Timothy M. McLean, Pamela J. Bacskai, Brian J. TI Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson's Disease SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Parkinson's disease; Dementia with Lewy bodies; Lewy bodies; Lewy Neurites; Alpha-Synuclein; Blood-brain barrier; In vivo imaging; Molecular imaging; PET ID POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; ALPHA-SYNUCLEIN; DOPAMINE TRANSPORTER; ALZHEIMERS-DISEASE; LEWY BODIES; AMYLOID-BETA; BRAIN; PROTEIN; QUANTIFICATION AB The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson's disease (PD) pathology, and be detectable with one or more imaging modalities. A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson's and Alzheimer's disease tissue, alpha-synuclein oligomers and inclusions in two cell culture models, and alpha-synuclein aggregates in cortical neurons of a transgenic mouse model. Finally, compounds were tested for blood-brain barrier permeability using intravital microscopy. Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer's pathology. The cell culture models and transgenic mouse models that exhibit alpha-synuclein aggregation did not prove predictive for ligand binding. The compounds had favorable physicochemical properties, and several were brain permeable. Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology. C1 [Neal, Krista L.; Shakerdge, Naomi B.; Hou, Steven S.; Bacskai, Brian J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Klunk, William E.; Mathis, Chester A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Nesterov, Evgueni E.] MIT, Dept Chem, Cambridge, MA 02139 USA. [McLean, Pamela J.] Mayo Clin Florida, Dept Neurosci, Jacksonville, FL 32224 USA. [Nesterov, Evgueni E.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org RI Swager, Timothy/H-7459-2012; OI Swager, Timothy/0000-0002-3577-0510; Klunk, William/0000-0001-5512-0251 FU Michael J. Fox Foundation; NIH [AG026240] FX Funding. Michael J. Fox Foundation and NIH AG026240. NR 27 TC 8 Z9 8 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD OCT PY 2013 VL 15 IS 5 BP 585 EP 595 DI 10.1007/s11307-013-0634-y PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 221GI UT WOS:000324645500010 PM 23624948 ER PT J AU Ghazani, AA McDermott, S Pectasides, M Sebas, M Mino-Kenudson, M Lee, H Weissleder, R Castro, CM AF Ghazani, Arezou A. McDermott, Shaunagh Pectasides, Melina Sebas, Matt Mino-Kenudson, Mari Lee, Hakho Weissleder, Ralph Castro, Cesar M. TI Comparison of select cancer biomarkers in human circulating and bulk tumor cells using magnetic nanoparticles and a miniaturized micro-NMR system SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Circulating tumor cells; Magnetic nanoparticles; Micro-NMR (mu NMR); Point-of-care diagnostics ID RESISTANT PROSTATE-CANCER; RESONANCE; SURVIVAL; PREDICT AB Circulating tumor cells (CTC) harvested from peripheral blood have received significant interest as sources for serial sampling to gauge treatment efficacy. Nanotechnology and microfluidic based approaches are emerging to facilitate such analyses. While of considerable clinical importance, there is little information on how similar or different CTCs are from their shedding bulk tumors. In this clinical study, paired tumor fine needle aspirate and peripheral blood samples were obtained from cancer patients during image-guided biopsy. Using targeted magnetic nanoparticles and a point-of-care micro-NMR system, we compared selected biomarkers (EpCAM, EGFR, HER-2 and vimentin) in both CTC and fine needle biopsies of solid epithelial cancers. We show a weak correlation between each paired sample, suggesting that use of CTC as "liquid biopsies" and proxies to metastatic solid lesions could be misleading. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ghazani, Arezou A.; McDermott, Shaunagh; Pectasides, Melina; Lee, Hakho; Weissleder, Ralph; Castro, Cesar M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Ghazani, Arezou A.; McDermott, Shaunagh; Pectasides, Melina; Sebas, Matt; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph; Castro, Cesar M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; castro.cesar@mgh.harvard.edu FU [2R01EB004626]; [U54-CA151884]; [DOD W81XWH-11-1-0706]; [K12CA087723] FX This work was funded in part by 2R01EB004626, U54-CA151884, DOD W81XWH-11-1-0706, and K12CA087723. NR 45 TC 9 Z9 9 U1 5 U2 54 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD OCT PY 2013 VL 9 IS 7 BP 1009 EP 1017 DI 10.1016/j.nano.2013.03.011 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 219PU UT WOS:000324520900018 PM 23570873 ER PT J AU Mir, Y Elrington, SA Hasan, T AF Mir, Youssef Elrington, Stefan A. Hasan, Tayyaba TI A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Targeted photodynamic therapy; EGFR; Liposome; Ovarian cancer; Drug delivery ID PHASE-II TRIAL; PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODY; IN-VITRO; PHOTOPHYSICAL PROPERTIES; PROTEIN-BINDING; KINASE PATHWAY; EGFR; PORPHYRIN; LIPOSOMES AB Targeted photodynamic therapy (TPDT) involves the administration of a photosensitizer (PS) conjugated with a targeting moiety followed by light activation. The systemic toxicity associated with conventional therapy may thus be significantly reduced in TPDT due to the dual selectivity provided by the spatial localization of the illumination as well as the target-localizing ability of the conjugate. Herein, a photo-immuno-conjugate-associating-liposome (PICAL) for TPDT has been developed in which the FDA approved benzoporphyrin derivative monoacid A (BPD) and the Cetuximab antibody for epidermal growth factor receptor (EGFR) were associated into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. Results have shown that the BPD molecules adsorbed into PICAL have stable optical behavior and a higher fluorescence quantum yield than free-BPD. The Cetuximab adsorbed into PPL selectively binds to cells that overexpress EGFR. The inhibition of EGFR signaling by PICAL has enhanced PDT-mediated ovarian cancer cell death. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mir, Youssef; Elrington, Stefan A.; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Bartlett Hall 314, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU National Institutes of Health (NIH) - National Cancer Institute (NCI) [R01CA156177, R01CA160998]; Fonds quebecois de la recherche sur la nature et les technologies (FQRNT), Quebec, Canada FX This study was supported by the National Institutes of Health (NIH) - National Cancer Institute (NCI) Grants R01CA156177 and R01CA160998. Y. Mir acknowledges funding from Fonds quebecois de la recherche sur la nature et les technologies (FQRNT), Quebec, Canada. NR 47 TC 20 Z9 21 U1 4 U2 46 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD OCT PY 2013 VL 9 IS 7 BP 1114 EP 1122 DI 10.1016/j.nano.2013.02.005 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 219PU UT WOS:000324520900029 PM 23485748 ER PT J AU Kim, W Bird, GH Neff, T Guo, GJ Kerenyi, MA Walensky, LD Orkin, SH AF Kim, Woojin Bird, Gregory H. Neff, Tobias Guo, Guoji Kerenyi, Marc A. Walensky, Loren D. Orkin, Stuart H. TI Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer SO NATURE CHEMICAL BIOLOGY LA English DT Article ID GROUP PROTEIN EZH2; HISTONE METHYLTRANSFERASE ACTIVITY; S-ADENOSYLHOMOCYSTEINE HYDROLASE; PROSTATE-CANCER; DNA METHYLATION; LYSINE 27; POLYCOMB; CELLS; H3; TRANSFORMATION AB Enhancer of zeste homolog 2 (EZH2) is the histone lysine N-methyltransferase component of the Polycomb repressive complex 2 (PRC2), which, in conjunction with embryonic ectoderm development (EED) and suppressor of zeste 12 homolog, regulates cell lineage determination and homeostasis. Enzymatic hyperactivity has been linked to aberrant repression of tumor suppressor genes in diverse cancers. Here, we report the development of stabilized alpha-helix of EZH2 (SAH-EZH2) peptides that selectively inhibit H3 Lys27 trimethylation by dose-responsively disrupting the EZH2-EED complex and reducing EZH2 protein levels, a mechanism distinct from that reported for small-molecule EZH2 inhibitors targeting the enzyme catalytic domain. MLL-AF9 leukemia cells, which are dependent on PRC2, undergo growth arrest and monocyte-macrophage differentiation upon treatment with SAH-EZH2, consistent with observed changes in expression of PRC2-regulated, lineage-specific marker genes. Thus, by dissociating the EZH2-EED complex, we pharmacologically modulate an epigenetic 'writer' and suppress PRC2-dependent cancer cell growth. C1 [Kim, Woojin; Guo, Guoji; Kerenyi, Marc A.; Walensky, Loren D.; Orkin, Stuart H.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. [Kim, Woojin; Bird, Gregory H.; Guo, Guoji; Kerenyi, Marc A.; Walensky, Loren D.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Woojin; Bird, Gregory H.; Guo, Guoji; Kerenyi, Marc A.; Walensky, Loren D.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Linde Program Canc Chem Biol, Boston, MA 02115 USA. [Neff, Tobias] Univ Colorado, Aurora, CO USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. EM loren_walensky@dfci.harvard.edu; stuart_orkin@dfci.harvard.edu OI Neff, Tobias/0000-0002-0188-8393 FU US National Institutes of Health [U01CA105423, 5R01GM090299]; Leukemia and Lymphoma Society Specialized Center of Research project grant FX We thank E. Smith for graphics assistance. This work was supported by US National Institutes of Health grant U01CA105423 to S.H.O. and 5R01GM090299 and a Leukemia and Lymphoma Society Specialized Center of Research project grant to L.D.W. S.H.O. is an Investigator of the Howard Hughes Medical Institute. NR 51 TC 118 Z9 122 U1 1 U2 50 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD OCT PY 2013 VL 9 IS 10 BP 643 EP 650 DI 10.1038/NCHEMBIO.1331 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226MZ UT WOS:000325041800012 PM 23974116 ER PT J AU Yoshida, T Georgopoulos, K AF Yoshida, Toshimi Georgopoulos, Katia TI GATA-3 controls self-renewal in stressed HSCs SO NATURE IMMUNOLOGY LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS; MAINTENANCE AB The transcription factor GATA-3 is expressed in quiescent hematopoietic stem cells (HSCs) with long-term repopulating ability. Stress-mediated activation of HSCs promotes localization of GATA-3 to the nucleus in a manner dependent on the mitogen-activated protein kinase p38 alpha and restricts self-renewal. C1 [Yoshida, Toshimi; Georgopoulos, Katia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Yoshida, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2013 VL 14 IS 10 BP 1032 EP 1033 DI 10.1038/ni.2715 PG 3 WC Immunology SC Immunology GA 220LH UT WOS:000324584700010 PM 24048133 ER PT J AU Dubin, RF Teerlink, JR Schiller, NB Alokozai, D Peralta, CA Johansen, KL AF Dubin, Ruth F. Teerlink, John R. Schiller, Nelson B. Alokozai, Dean Peralta, Carmen A. Johansen, Kirsten L. TI Association of segmental wall motion abnormalities occurring during hemodialysis with post-dialysis fatigue SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE end-stage renal disease; hemodialysis; post-dialysis fatigue ID DIALYSIS; DYSFUNCTION; DEPRESSION; MORTALITY; OUTCOMES; IMPACT AB Post-dialysis fatigue (PDF) is a common, debilitating symptom that remains poorly understood. Cardiac wall motion abnormalities (WMAs) may worsen during dialysis, but it is unknown whether WMA are associated with PDF. Forty patients were recruited from University of California San Francisco-affiliated dialysis units between January 2010 and February 2011. Participants underwent echocardiograms before and during the last hour of 79 dialysis sessions. Myocardial segments were graded 14 by a blinded reviewer, with four representing the worst WMA, and the segmental scores were summed for each echocardiogram. Patients completed questionnaires about their symptoms. Severe PDF (defined as lasting 2 h after dialysis) was analysed using a generalized linear model with candidate predictors including anemia, intradialytic hemodynamics and cardiac function. Forty-four percent of patients with worsened WMA (n9) had severe PDF, compared with 13 of patients with improved or unchanged WMA (P 0.04). A one-point increase in the WMA score during dialysis was associated with a 10 higher RR of severe PDF [RR: 1.1, 95 CI (1.1, 1.2), P 0.001]. After multivariable adjustment, every point increase in the WMA score was associated with a 2-fold higher risk of severe PDF [RR: 1.9, 95 CI (1.4, 2.6), P 0.001]. History of depression was associated with severe PDF after adjustment for demographics and comorbidities [RR: 3.4, 95 CI (1.3, 9), P 0.01], but anemia, hemodynamics and other parameters of cardiac function were not. Although cross-sectional, these results suggest that some patients may experience severe PDF as a symptom of cardiac ischemia occurring during dialysis. C1 [Dubin, Ruth F.; Peralta, Carmen A.; Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med Nephrol, San Francisco, CA 94143 USA. [Teerlink, John R.; Schiller, Nelson B.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med Cardiol, San Francisco, CA 94143 USA. [Alokozai, Dean] Cardiocore, San Francisco, CA USA. RP Dubin, RF (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med Nephrol, San Francisco, CA 94143 USA. EM ruth.dubin@ucsf.edu FU University of California San Francisco Academic Senate, San Francisco, CA, USA; Research Evaluation and Allocation Committee in the University of California San Francisco, School of Medicine Dean's Office, San Francisco, CA, USA; National Institute of Diabetes and Digestive and Kidney Diseases [1K24-DK085153-02, 1K23-DK092354-01A1]; UCSF Clinical and Translational Science Institute [UL1 TR000004] FX Funding for this project came from the following sources. (i) Individual Investigator Grant, University of California San Francisco Academic Senate, San Francisco, CA, USA. (ii) Grant Huntington Fund provided by the Research Evaluation and Allocation Committee in the University of California San Francisco, School of Medicine Dean's Office, San Francisco, CA, USA. (iii) National Institute of Diabetes and Digestive and Kidney Diseases, 1K24-DK085153-02. (iv) National Institute of Diabetes and Digestive and Kidney Diseases, 1K23-DK092354-01A1. (v) UCSF Clinical and Translational Science Institute grant number UL1 TR000004. NR 18 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2013 VL 28 IS 10 BP 2580 EP 2585 DI 10.1093/ndt/gft097 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 228JU UT WOS:000325183100024 PM 23743019 ER PT J AU Wubben, TJ Eghrari, AO Mccoy, AN Ramsey, DJ AF Wubben, T. J. Eghrari, A. O. Mccoy, A. N. Ramsey, D. J. TI Optic Atrophy in End-Stage Giant Axonal Neuropathy: A Case Report SO NEURO-OPHTHALMOLOGY LA English DT Article DE Giant axonal neuropathy; non-glaucomatous cupping; OCT; optic atrophy; retinal nerve fibre layer ID NERVE-FIBER LAYER; COHERENCE TOMOGRAPHY; MULTIPLE-SCLEROSIS; GLAUCOMA; DEGRADATION; GIGAXONIN; PATHWAY; PROTEIN; EYES; NEURODEGENERATION AB A 32-year-old woman with a history of biopsy-proven giant axonal neuropathy (GAN) and no past ocular history presented after failing a vision-screening test conducted by her primary doctor. Bilateral optic atrophy was observed on fundus examination with cup-to-disc ratio of 0.7. Kinetic visual fields showed moderate constriction in both eyes. Optical coherence tomography (OCT) of the retinal nerve fibre layer (RNFL) exhibited diffuse thinning, a pattern atypical of glaucomatous or nutritional optic atrophy and most likely secondary to the optic atrophy associated with GAN. Serial OCT to monitor RNFL thickness may offer a non-invasive means of monitoring progression in GAN for future therapeutic studies. C1 [Wubben, T. J.] Univ Illinois, Chicago, IL USA. [Eghrari, A. O.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Mccoy, A. N.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. [Ramsey, D. J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ramsey, DJ (reprint author), Harvard Univ, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM ramsey@post.harvard.edu NR 27 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PD OCT PY 2013 VL 37 IS 5 BP 209 EP 213 DI 10.3109/01658107.2013.814149 PG 5 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 224MX UT WOS:000324892200005 PM 28167990 ER PT J AU Kornblum, C Nicholls, T Haack, TB Schoeler, S Peeva, V Danhauser, K Hallmann, K Zsurka, G Rorbach, J Iuso, A Wieland, T Sciacco, M Ronchi, D Comi, GP Moggio, M Quinzii, CM DiMauro, S Calvo, SE Mootha, VK Klopstock, T Strom, TM Meitinger, T Minczuk, M Kunz, WS Prokisch, H AF Kornblum, C. Nicholls, T. Haack, T. B. Schoeler, S. Peeva, V. Danhauser, K. Hallmann, K. Zsurka, G. Rorbach, J. Iuso, A. Wieland, T. Sciacco, M. Ronchi, D. Comi, G. P. Moggio, M. Quinzii, C. M. DiMauro, S. Calvo, S. E. Mootha, V. K. Klopstock, T. Strom, T. M. Meitinger, T. Minczuk, M. Kunz, W. S. Prokisch, H. TI Loss of function of MGME1, a novel player in mitochondrial DNA replication, causes a distinct autosomal recessive mitochondrial disorder SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 18th International Congress of the World-Muscle-Society (WMS) CY OCT 01-05, 2013 CL CA SP World Muscle Soc C1 [Kornblum, C.] Univ Hosp Bonn, Bonn, Germany. [Nicholls, T.; Rorbach, J.; Minczuk, M.] MRC, Mitochondrial Biol Unit, Cambridge, England. [Haack, T. B.; Danhauser, K.; Iuso, A.; Wieland, T.; Strom, T. M.; Meitinger, T.; Prokisch, H.] Tech Univ Munich, D-80290 Munich, Germany. [Haack, T. B.; Danhauser, K.; Iuso, A.; Wieland, T.; Strom, T. M.; Meitinger, T.; Prokisch, H.] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany. [Haack, T. B.; Danhauser, K.; Iuso, A.; Wieland, T.; Strom, T. M.; Meitinger, T.; Prokisch, H.] German Res Ctr Environm Hlth, Munich, Germany. [Schoeler, S.; Peeva, V.; Hallmann, K.; Zsurka, G.; Kunz, W. S.] Univ Hosp Bonn, Bonn, Germany. [Schoeler, S.; Peeva, V.; Hallmann, K.; Zsurka, G.; Kunz, W. S.] Life & Brain Ctr, Bonn, Germany. [Sciacco, M.; Moggio, M.] Univ Milan, Osped Maggiore Policlin, Neuromuscular Unit, Milan, Italy. [Ronchi, D.; Comi, G. P.] Univ Milan, Osped Maggiore Policlin, Neurol Unit, Milan, Italy. [Quinzii, C. M.; DiMauro, S.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Calvo, S. E.; Mootha, V. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Syst Biol, Broad Inst Cambridge,Dept Mol Biol & Med, Boston, MA USA. [Klopstock, T.] Univ Munich, Friedrich Baur Inst, Munich, Germany. RI Prokisch, Holger/N-8964-2013; Comi, Giacomo /K-5702-2016; Ronchi, Dario/K-8011-2016 OI Comi, Giacomo /0000-0002-1383-5248; Ronchi, Dario/0000-0002-6093-9816 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2013 VL 23 IS 9-10 BP 852 EP 852 DI 10.1016/j.nmd.2013.06.734 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225OP UT WOS:000324972500360 ER PT J AU Kim, SW Hooker, JM Otto, N Win, K Muench, L Shea, C Carter, P King, P Reid, AE Volkow, ND Fowler, JS AF Kim, Sung Won Hooker, Jacob M. Otto, Nicola Win, Khaing Muench, Lisa Shea, Colleen Carter, Pauline King, Payton Reid, Alicia E. Volkow, Nora D. Fowler, Joanna S. TI Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE C-11]valproic acid; [C-11]butyric acid; [C-11]4-phenylbutyric acid; Pharmacokinetics; Positron emission tomography; Histone deacetylase (HDAC) ID HISTONE DEACETYLASE INHIBITORS; INCREASED FETAL-HEMOGLOBIN; BETA-GLOBIN DISORDERS; DISEASE MOUSE MODEL; SODIUM-BUTYRATE; ULCERATIVE-COLITIS; COLONIC-MUCOSA; IN-VIVO; PHENYLBUTYRATE; MEMORY AB The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using (CO2)-C-11 and the appropriate Grignard reagents. [C-11]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity were the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low (<0.006%ID/cc, BA > VPA > PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [C-11]BA showed relatively high uptake in spleen and pancreas whereas [C-11]PBA showed high uptake in liver and heart. Notably, [C-11]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of releVance in understanding their therapeutic and side effect profile including their teratogenic effects. Published by Elsevier Inc. C1 [Kim, Sung Won; Muench, Lisa; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Upton, NY 11973 USA. [Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA USA. [Otto, Nicola] Johannes Gutenberg Univ Mainz, Inst Organ Chem, D-55122 Mainz, Germany. [Win, Khaing] St Josephs Coll, Dept Biol & Chem, Brooklyn, NY USA. [Shea, Colleen; Carter, Pauline; King, Payton; Fowler, Joanna S.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Reid, Alicia E.] CUNY Medgar Evers Coll, Brooklyn, NY 11225 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Kim, SW (reprint author), NIAAA, Lab Neuroimaging, Upton, NY 11973 USA. EM sunny.kim@nih.gov; hooker@nmr.mgh.harvard.edu OI Hooker, Jacob/0000-0002-9394-7708 FU U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-98CH10886]; NIH Intramural Program of the National Institute on Alcohol Abuse and Alcoholism; BNL Science Undergraduate Laboratory Internship Program; Deutscher Akademischer Austauschdienst (DAAD), Bonn, Germany; [1R01DA030321] FX This work was performed at Brookhaven National Laboratory (BNL) with infrastructure support from the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-98CH10886. The NIH Intramural Program of the National Institute on Alcohol Abuse and Alcoholism (SWK, LM, NDV) and grant 1R01DA030321 (JMH, SWK) provided research support. Additional support was provided by the BNL Science Undergraduate Laboratory Internship Program (KW) and the Deutscher Akademischer Austauschdienst (DAAD), Bonn, Germany (NO). We thank Michael Schueller for cyclotron operations and Donald Warner for PET operations. NR 48 TC 12 Z9 12 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2013 VL 40 IS 7 BP 912 EP 918 DI 10.1016/j.nucmedbio.2013.06.007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 221JW UT WOS:000324656100008 PM 23906667 ER PT J AU Smith, SD Singh, K Lin, SC Chen, PP Chen, TC Francis, BA Jampel, HD AF Smith, Scott D. Singh, Kuldev Lin, Shan C. Chen, Philip P. Chen, Teresa C. Francis, Brian A. Jampel, Henry D. TI Evaluation of the Anterior Chamber Angle in Glaucoma A Report by the American Academy of Ophthalmology SO OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; LASER PERIPHERAL IRIDOTOMY; ULTRASOUND BIOMICROSCOPY GONIOSCOPY; RELATIVE PUPILLARY BLOCK; CLOSURE GLAUCOMA; DEPTH ANALYZER; SEGMENT-OCT; NARROW ANGLES; ASIAN EYES; QUANTITATIVE-EVALUATION AB Objective: To assess the published literature pertaining to the association between anterior segment imaging and gonioscopy and to determine whether such imaging aids in the diagnosis of primary angle closure (PAC). Methods: Literature searches of the PubMed and Cochrane Library databases were last conducted on July 6, 2011. The searches yielded 371 unique citations. Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the titles and abstracts of these articles and selected 134 of possible clinical significance for further review. The panel reviewed the full text of these articles and identified 79 studies meeting the inclusion criteria, for which the panel methodologist assigned a level of evidence based on a standardized grading scheme adopted by the American Academy of Ophthalmology. Three, 70, and 6 studies were rated as providing level I, II, and III evidence, respectively. Results: Quantitative and qualitative parameters defined from ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (OCT), Scheimpflug photography, and the scanning peripheral anterior chamber depth analyzer (SPAC) demonstrate a strong association with the results of gonioscopy. There is substantial variability in the type of information obtained from each imaging method. Imaging of structures posterior to the iris is possible only with UBM. Direct imaging of the anterior chamber angle (ACA) is possible using UBM and OCT. The ability to acquire OCT images in a completely dark environment allows greater sensitivity in detecting eyes with appositional angle closure. Noncontact imaging using OCT, Scheimpflug photography, or SPAC makes these methods more attractive for large-scale PAC screening than contact imaging using UBM. Conclusions: Although there is evidence suggesting that anterior segment imaging provides useful information in the evaluation of PAC, none of these imaging methods provides sufficient information about the ACA anatomy to be considered a substitute for gonioscopy. Longitudinal studies are needed to validate the diagnostic significance of the parameters measured by these instruments for prospectively identifying individuals at risk for PAC. C1 [Smith, Scott D.] Cleveland Clin Abu Dhabi, Abu Dhabi, U Arab Emirates. [Singh, Kuldev] Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA. [Lin, Shan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Chen, Philip P.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. [Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, Boston, MA USA. [Francis, Brian A.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. [Jampel, Henry D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Glaucoma Ctr Excellence, Baltimore, MD 21205 USA. RP Smith, SD (reprint author), Care of Emptage N, Amer Acad Ophthalmol Qual Care & Knowledge Base D, 655 Beach St, San Francisco, CA 94109 USA. FU American Academy of Ophthalmology FX Funded without commercial support by the American Academy of Ophthalmology. NR 93 TC 18 Z9 19 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2013 VL 120 IS 10 BP 1985 EP 1997 DI 10.1016/j.ophtha.2013.05.034 PG 13 WC Ophthalmology SC Ophthalmology GA 227CQ UT WOS:000325086400014 PM 23978623 ER PT J AU Schafer, AL Burghardt, AJ Sellmeyer, DE Palermo, L Shoback, DM Majumdar, S Black, DM AF Schafer, A. L. Burghardt, A. J. Sellmeyer, D. E. Palermo, L. Shoback, D. M. Majumdar, S. Black, D. M. TI Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS) SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bisphosphonate; Bone microstructure; Cortical; High-resolution peripheral quantitative computed tomography; Parathyroid hormone; Trabecular ID BONE-MINERAL DENSITY; QUANTITATIVE COMPUTED-TOMOGRAPHY; VERTEBRAL FRACTURE RISK; FINITE-ELEMENT-ANALYSIS; IN-VIVO ASSESSMENT; DISTAL RADIUS; CORTICAL BONE; HR-PQCT; INTRACORTICAL POROSITY; RANDOMIZED-TRIAL AB In postmenopausal women receiving combination parathyroid hormone (PTH) (1-84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Introduction PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1-84) and ibandronate. Methods Postmenopausal women with low bonemass (n=43) were treated with 6 months of PTH(1-84) (100 mu g/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy. Results Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p<0.01 for each). Cortical thickness and BMD decreased at the radius (p<0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p=0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p<0.01) but not radius. Stiffness and failure load decreased at the radius (p<0.0001) but did not change at the tibia. Conclusions Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy. C1 [Schafer, A. L.; Shoback, D. M.] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, CA 94121 USA. [Schafer, A. L.; Shoback, D. M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Burghardt, A. J.; Majumdar, S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Sellmeyer, D. E.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Palermo, L.; Black, D. M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Schafer, AL (reprint author), San Francisco VA Med Ctr, Endocrine Res Unit, 4150 Clement St,111N, San Francisco, CA 94121 USA. EM anne.schafer@ucsf.edu FU Genentech, Inc.; NPS Pharmaceuticals [PTH[1-84]]; Genentech; Bayer; Department of Veterans Affairs through an Advanced Fellowship in Women's Health; Career Development Award [5 IK2 CX000549-02]; Research Enhancement Award Program; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R01-AR055588, R01-AR060700]; NIAMS; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering [R01-AG017762] FX The PICS trial was supported by an investigator-initiated grant (to DMB) from Genentech, Inc., a member of the Roche group. The sponsor was involved in study design but not in the collection, analysis, or interpretation of data, nor in the writing of the article. Study drugs were supplied by NPS Pharmaceuticals (PTH[1-84]), Genentech (ibandronate), and Bayer (calcium citrate+D3). Reagents for bone turnover marker assays were provided by Roche Diagnostics. The authors have full control of all data. Additional support was provided by the Department of Veterans Affairs through an Advanced Fellowship in Women's Health (to ALS), a Career Development Award under contract 5 IK2 CX000549-02 (to ALS), and the Research Enhancement Award Program (to DMS); by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under contracts R01-AR055588 (to DMS) and R01-AR060700 (to AJB); and by NIAMS, the National Institute on Aging, and the National Institute of Biomedical Imaging and Bioengineering under contract R01-AG017762 (to SM). The authors thank Jean Hietpas, Lucy Wu, and Laurel Denton for their roles in study direction and data coordination; Rayshawnda Davis, Natasha Rathbun, Andrea Hacker, and Makani da Silva for study coordination and DXA scan acquisition; Melissa Guan, Thelma Munoz, and S. Paran Yap for their roles in HR-pQCT coordination, image acquisition, and analysis; and Richard Eastell, MD, and Fatma Gossiel for analysis of bone turnover markers. NR 48 TC 12 Z9 12 U1 0 U2 9 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD OCT PY 2013 VL 24 IS 10 BP 2591 EP 2601 DI 10.1007/s00198-013-2349-y PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 219UN UT WOS:000324536200006 PM 23589163 ER PT J AU Reda, H Greene, K Rice, FL Rowbotham, MC Petersen, KL AF Reda, Haatem Greene, Kaitlin Rice, Frank L. Rowbotham, Michael C. Petersen, Karin L. TI Natural history of herpes zoster: Late follow-up of 3.9 years (n=43) and 7.7 years (n=10) SO PAIN LA English DT Article DE Capsaicin response test; Chronic pain; Postherpetic neuralgia; Quantitative sensory testing; Thermal ID POSTHERPETIC NEURALGIA; SURGICAL REMOVAL; PAINFUL SKIN; ALLODYNIA; PERSISTENCE; DEFINITION; PREDICTORS; RELIEF; BURDEN; PHN AB Postherpetic neuralgia (PHN) is a common complication after herpes zoster (HZ). Subjects who completed a longitudinal observational 6-month study (4 visits) of the natural history of HZ were recontacted for 2 additional follow-up visits that included pain and sensory symptom assessment, quantitative sensory testing, capsaicin response test, and 3-mm punch skin biopsies in HZ-affected, mirror-image, and control skin sites. Forty-three subjects (14 with PHN at 6 months) of the original 94 subjects in the cohort were comprehensively assessed at a median 3.9 years after HZ onset (visit 5), and 10 subjects underwent a final assessment at a median 7.7 years after HZ onset (visit 6). At 3.9 years, none of the 29 subjects who had been pain free at 6 months had a recurrence of pain. Only 2 of the 14 subjects with PHN at 6 months still had pain at 3.9 years. One subject with PHN at 6 months was free of symptoms at 3.9 years but had very mild pain at 7.7 years. Sensory function continued on a path toward normalization, but was still abnormal in many subjects, especially those who met criteria for PHN at 6 months. Even at 7.7 years, reinnervation of HZ-affected skin was not apparent. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Reda, Haatem] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Greene, Kaitlin; Rowbotham, Michael C.; Petersen, Karin L.] CPMC Res Inst, San Francisco, CA 94107 USA. [Rice, Frank L.] Albany Med Coll, Albany, NY 12208 USA. RP Petersen, KL (reprint author), CPMC Res Inst, 475 Brannan,Suite 220, San Francisco, CA 94107 USA. EM peterskp@cpmcri.org FU CPMCRI Neuropathic Pain Research Gift Fund; CPMCRI Medical Student Research Fellowship Gift Fund; NINDS [R0-1 NS39521, K24 NS02164] FX Supported by the CPMCRI Neuropathic Pain Research Gift Fund, the CPMCRI Medical Student Research Fellowship Gift Fund, and NINDS Grants R0-1 NS39521 (Drs Petersen and Rowbotham) and K24 NS02164 (Dr Rowbotham). NR 32 TC 8 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2013 VL 154 IS 10 BP 2227 EP 2233 DI 10.1016/j.pain.2013.04.015 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 219AK UT WOS:000324475500041 PM 23719573 ER PT J AU Chahine, LM Daley, J Horn, S Duda, JE Colcher, A Hurtig, H Cantor, C Dahodwala, N AF Chahine, Lama M. Daley, Joseph Horn, Stacy Duda, John E. Colcher, Amy Hurtig, Howard Cantor, Charles Dahodwala, Nabila TI Association between dopaminergic medications and nocturnal sleep in early-stage Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article ID REM-SLEEP; BEHAVIOR DISORDER; L-DOPA; PRAMIPEXOLE; SYMPTOMS; RECEPTOR; RAT; MICROSTRUCTURE; WAKEFULNESS; LEVODOPA AB Background: Poor nocturnal sleep is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopaminergic drugs influence nocturnal sleep in PD, particularly in relation to medication timing. We examined the association between dopaminergic medications and subjective and objective nocturnal sleep in PD. Methods: Individuals with PD were recruited from the outpatient clinic. Demographics and disease information were collected. Patients underwent one-night polysomnography and responded to SCOPA-SLEEP, a self-administered questionnaire which includes a section on nighttime sleep and an overall measure of sleep quality; higher scores indicate worse sleep. Medication intake, including medication timing in relation to bedtime, was obtained and converted to levodopa equivalents. Results: 41 Males and 21 females, median age 63.9 years, participated. Median disease duration was 5 years. After adjusting for age, sex, disease severity, and disease duration, greater total levodopa equivalent intake within 4 h of sleep was associated with higher total SCOPA-nighttime score (p = 0.009) and greater wake time after sleep onset (p = 0.049). Greater dopaminergic medication intake prior to sleep was also associated with less rapid eye movement (REM) sleep as a percent of total sleep time (p = 0.004). Conclusions: Higher amounts of dopaminergic medications taken prior to sleep were associated with poor sleep quality and less REM sleep. Although poor nocturnal sleep in PD is likely multi-factorial in etiology, our findings suggest that timing and dose of medications prior to sleep need to be considered in its management. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Chahine, Lama M.; Horn, Stacy; Duda, John E.; Colcher, Amy; Hurtig, Howard; Cantor, Charles; Dahodwala, Nabila] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19107 USA. [Chahine, Lama M.; Cantor, Charles] Univ Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19107 USA. [Daley, Joseph] Univ Alabama Birmingham, Sch Med, Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Daley, Joseph] Univ Alabama Birmingham, Sch Med, Dept Neurol, Birmingham, AL 35233 USA. [Duda, John E.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. RP Chahine, LM (reprint author), Univ Penn, Perelman Sch Med, Dept Neurol, 330 S 9th St, Philadelphia, PA 19107 USA. EM lamachahine@hotmail.com NR 38 TC 13 Z9 14 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD OCT PY 2013 VL 19 IS 10 BP 859 EP 863 DI 10.1016/j.parkreldis.2013.05.009 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 223EZ UT WOS:000324788800002 PM 23751512 ER PT J AU Johnson, TJ Weaver, MD Borrero, S Davis, EM Myaskovsky, L Zuckerbraun, NS Kraemer, KL AF Johnson, Tiffani J. Weaver, Matthew D. Borrero, Sonya Davis, Esa M. Myaskovsky, Larissa Zuckerbraun, Noel S. Kraemer, Kevin L. TI Association of Race and Ethnicity With Management of Abdominal Pain in the Emergency Department SO PEDIATRICS LA English DT Article DE abdominal pain; disparities; emergency department; racial difference ID ANALGESIC TREATMENT; TRAUMA PATIENTS; CLINICAL-TRIAL; PUBLIC-HEALTH; CHEST-PAIN; DISPARITIES; CHILDREN; RACE/ETHNICITY; CARE; QUALITY AB OBJECTIVE: To determine if race/ethnicity-based differences exist in the management of pediatric abdominal pain in emergency departments (EDs). METHODS: Secondary analysis of data from the 2006-2009 National Hospital Ambulatory Medical Care Survey regarding 2298 visits by patients <= 21 years old who presented to EDs with abdominal pain. Main outcomes were documentation of pain score and receipt of any analgesics, analgesics for severe pain (defined as >= 7 on a 10-point scale), and narcotic analgesics. Secondary outcomes included diagnostic tests obtained, length of stay (LOS), 72-hour return visits, and admission. RESULTS: Of patient visits, 70.1% were female, 52.6% were from non-Hispanic white, 23.5% were from non-Hispanic black, 20.6% were from Hispanic, and 3.3% were from "other" racial/ethnic groups; patients' mean age was 14.5 years. Multivariate logistic regression models adjusting for confounders revealed that non-Hispanic black patients were less likely to receive any analgesic (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.43-0.87) or a narcotic analgesic (OR: 0.38; 95% CI: 0.18-0.81) than non-Hispanic white patients (referent group). This finding was also true for non-Hispanic black and "other" race/ethnicity patients with severe pain (ORs [95% CI]: 0.43 [0.22-0.87] and 0.02 [0.00-0.19], respectively). Non-Hispanic black and Hispanic patients were more likely to have a prolonged LOS than non-Hispanic white patients (ORs [95% CI]: 1.68 [1.13-2.51] and 1.64 [1.09-2.47], respectively). No significant race/ethnicity-based disparities were identified in documentation of pain score, use of diagnostic procedures, 72-hour return visits, or hospital admissions. CONCLUSIONS: Race/ethnicity-based disparities exist in ED analgesic use and LOS for pediatric abdominal pain. Recognizing these disparities may help investigators eliminate inequalities in care. C1 [Johnson, Tiffani J.] Childrens Hosp Philadelphia, Div Pediat Emergency Med, Philadelphia, PA 19104 USA. [Johnson, Tiffani J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Weaver, Matthew D.; Kraemer, Kevin L.] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. [Borrero, Sonya; Davis, Esa M.; Myaskovsky, Larissa; Kraemer, Kevin L.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Zuckerbraun, Noel S.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Pediat Emergency Med, Pittsburgh, PA 15261 USA. [Borrero, Sonya; Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Johnson, TJ (reprint author), Childrens Hosp Philadelphia, Div Pediat Emergency Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM johnsont6@email.chop.edu FU Agency for Healthcare Research and Quality [T32HS017587] FX Supported by grant T32HS017587 from the Agency for Healthcare Research and Quality to Drs Johnson and Kraemer. NR 38 TC 21 Z9 22 U1 2 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2013 VL 132 IS 4 BP E851 EP E858 DI 10.1542/peds.2012-3127 PG 8 WC Pediatrics SC Pediatrics GA 227FI UT WOS:000325095400006 PM 24062370 ER PT J AU Lomond, KV Henry, SM Jacobs, JV Hitt, JR Horak, FB Cohen, RG Schwartz, D Dumas, JA Naylor, MR Watts, R DeSarno, MJ AF Lomond, Karen V. Henry, Sharon M. Jacobs, Jesse V. Hitt, Juvena R. Horak, Fay B. Cohen, Rajal G. Schwartz, Daniel Dumas, Julie A. Naylor, Magdalena R. Watts, Richard DeSarno, Michael J. TI Protocol to assess the neurophysiology associated with multi-segmental postural coordination SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE postural coordination; MRI; EMG; cerebral cortex; multi-segmental ID LOW-BACK-PAIN; LIMB MOVEMENT; ADJUSTMENTS; SIGNALS; PEOPLE; CORTEX AB Anticipatory postural adjustments (APAs) stabilize potential disturbances to posture caused by movement. Impaired APAs are common with disease and injury. Brain functions associated with generating APAs remain uncertain due to a lack of paired tasks that require similar limb motion from similar postural orientations, but differ in eliciting an APA while also being compatible with brain imaging techniques (e. g., functional magnetic resonance imaging; fMRI). This study developed fMRI-compatible tasks differentiated by the presence or absence of APAs during leg movement. Eighteen healthy subjects performed two leg movement tasks, supported leg raise (SLR) and unsupported leg raise (ULR), to elicit isolated limb motion (no APA) versus multi-segmental coordination patterns (including APA), respectively. Ground reaction forces under the feet and electromyographic activation amplitudes were assessed to determine the coordination strategy elicited for each task. Results demonstrated that the ULR task elicited a multi-segmental coordination that was either minimized or absent in the SLR task, indicating that it would serve as an adequate control task for fMRI protocols. A pilot study with a single subject performing each task in an MRI scanner demonstrated minimal head movement in both tasks and brain activation patterns consistent with an isolated limb movement for the SLR task versus multi-segmental postural coordination for the ULR task. C1 [Lomond, Karen V.] Cent Michigan Univ, Sch Hlth Sci, Mt Pleasant, MI 48859 USA. [Lomond, Karen V.; Henry, Sharon M.; Jacobs, Jesse V.; Hitt, Juvena R.] Univ Vermont, Dept Rehabil & Movement Sci, Burlington, VT USA. [Horak, Fay B.; Cohen, Rajal G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Cohen, Rajal G.] Univ Idaho, Dept Psychol & Commun Studies, Moswow, ID 83843 USA. [Schwartz, Daniel] Portland VA Med Ctr, Methamphetamine Abuse Res Ctr, Portland, OR USA. [Schwartz, Daniel] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Schwartz, Daniel] Portland VA Med Ctr, Res Serv, Portland, OR USA. [Dumas, Julie A.; Naylor, Magdalena R.] Univ Vermont, Dept Psychiat, Burlington, VT 05405 USA. [Watts, Richard] Univ Vermont, MRI Ctr Bioimaging, Dept Radiol, Burlington, VT 05405 USA. [DeSarno, Michael J.] Univ Vermont, Dept Med Biostat, Burlington, VT 05405 USA. RP Lomond, KV (reprint author), Cent Michigan Univ, Sch Hlth Sci, Mt Pleasant, MI 48859 USA. EM lomon2k@cmich.edu FU National Institutes of Health [NIH2R01HD040909-06A2] FX The authors wish to thank our research subjects for their participation as well as Rebecca Ouelette-Morton and Kristen Zielinski for their assistance in data collection. The study was supported by the National Institutes of Health NIH2R01HD040909-06A2 (Principal Investigator: Henry SM). NR 21 TC 2 Z9 2 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 J9 PHYSIOL MEAS JI Physiol. Meas. PD OCT PY 2013 VL 34 IS 10 BP N97 EP N105 DI 10.1088/0967-3334/34/10/N97 PG 9 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA 224GN UT WOS:000324871100002 PM 24065623 ER PT J AU Sonnenberg, L Gelsomin, E Levy, DE Riis, J Barraclough, S Thorndike, AN AF Sonnenberg, Lillian Gelsomin, Emily Levy, Douglas E. Riis, Jason Barraclough, Susan Thorndike, Anne N. TI A traffic light food labeling intervention increases consumer awareness of health and healthy choices at the point-of-purchase SO PREVENTIVE MEDICINE LA English DT Article DE Nutrition labeling; Obesity; Food labeling ID NUTRITION; FRONT; RESTAURANTS; MENU; INFORMATION; LITERACY; ADULTS AB Objective. We surveyed customers in a hospital cafeteria in Boston, Massachusetts before and after implementation of traffic light food labeling to determine the effect of labels on customers' awareness and purchase of healthy foods. Methods. Cafeteria items were identified as red (unhealthy), yellow (less healthy), or green (healthy). Customers were interviewed before (N = 166) and after (N = 223) labeling was implemented. Each respondent was linked to cash register data to determine the proportion of red, yellow, and green items purchased. Data were collected from February-April 2010. We compared responses to survey questions and mean proportion of red, yellow, and green items per transaction between customers interviewed during baseline and customers interviewed during the intervention. Survey response rate was 60%. Results. Comparing responses during labeling intervention to baseline, more respondents identified health/nutrition as an important factor in their purchase (61% vs. 46%, p = 0.004) and reported looking at nutrition information (33% vs. 15%, p < 0.001). Respondents who noticed labels during the intervention and reported that labels influenced their purchases were more likely to purchase healthier items than respondents who did not notice labels (p < 0.001 for both). Conclusion. Traffic light food labels prompted individuals to consider their health and to make healthier choices at point-of-purchase. (C) 2013 Elsevier Inc. All rights reserved. C1 [Sonnenberg, Lillian; Gelsomin, Emily; Barraclough, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Riis, Jason] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Thorndike, Anne N.] Harvard Univ, Sch Med, Div Gen Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sonnenberg, L (reprint author), Massachusetts Gen Hosp, Ambulatory Nutr Serv, 165 Cambridge St,Suite 402, Boston, MA 02114 USA. EM lsonnenberg@partners.org; egelsomin@partners.org; Dlevy3@partners.org; jriis@hbs.edu; sbarraclough@partners.org; athorndike@partners.org FU NHLBI NIH HHS [K23 HL093221]; NIDDK NIH HHS [P30 DK040561] NR 33 TC 25 Z9 26 U1 10 U2 61 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD OCT PY 2013 VL 57 IS 4 BP 253 EP 257 DI 10.1016/j.ypmed.2013.07.001 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 223FC UT WOS:000324789100001 PM 23859926 ER PT J AU Economos, CD Hyatt, RR Must, A Goldberg, JP Kuder, J Naumova, EN Collins, JJ Nelson, ME AF Economos, Christina D. Hyatt, Raymond R. Must, Aviva Goldberg, Jeanne P. Kuder, Julia Naumova, Elena N. Collins, Jessica J. Nelson, Miriam E. TI Shape Up Somerville two-year results: A community-based environmental change intervention sustains weight reduction in children SO PREVENTIVE MEDICINE LA English DT Article DE Child health; Obesity; Fitness; Nutrition; BMI; Community; Intervention; Environmental change; Overweight ID SUMMER VACATION; SCHOOL; OBESITY; MASSACHUSETTS; OVERWEIGHT; PREVENTION; 21ST-CENTURY; CHILDHOOD; INCREASE; PROGRAM AB Objective: The objective of this study was to test the hypothesis that community-based environmental change intervention prevents undesirable weight gain in children. Method: The method used in this study was a two-year, non-randomized, controlled trial (2003-2005) using community-based,participatory methodology in three diverse cities in Massachusetts: one intervention and two socio-demographically-matched control communities (pooled for analysis). Children (n = 1028), with a mean age = 7.61 + 1.04 years participated. Interventions were made to improve energy balance by increasing physical activity options and availability of healthful foods (Year 1). To firmly secure sustainability, the study team supported policies and shifted intervention work to community members (Year 2). Results: Change in body mass index z-score (BMIz) was assessed by multiple regression, accounting for clustering within communities and adjusting for baseline covariates. Sex-specific overweight/obesity prevalence, incidence and remission were assessed. Over the two-year period, BMIz of children in the intervention community decreased by 0.06 [p = 0.005,95% confidence interval: 0.08 to 0.041 compared to controls. Prevalence of overweight/obesity decreased in males (OR = 0.61, p = 0.01) and females (OR = 0.78, p = 0.01) and remission increased in males (OR 3.18, p = 0.03) and females (OR 1.93,p = 0.03) in intervention compared to controls. Conclusion: Results demonstrate promise for preventing childhood obesity using a sustainable multi-level community-based model and reinforce the need for wide-reaching environmental and policy interventions. (C) 2013 Published by Elsevier Inc. C1 [Economos, Christina D.; Must, Aviva; Goldberg, Jeanne P.; Nelson, Miriam E.] Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA. [Hyatt, Raymond R.; Must, Aviva] Tufts Univ Sch Med, Boston, MA 02111 USA. [Kuder, Julia] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Naumova, Elena N.] Tufts Univ Sch Engn, Dept Civil & Environm Engn, Medford, MA 02155 USA. [Collins, Jessica J.] Healthier Community, Springfield, MA 01105 USA. RP Economos, CD (reprint author), Tufts Univ, Friedman Sch Nutr Sci & Policy, New Balance Chair Childhood Nutr, 150 Harrison Ave, Boston, MA 02111 USA. EM christina.economos@tufts.edu OI Naumova, Elena/0000-0002-9562-4734 FU Centers for Disease Control and Prevention (CDC), Atlanta [R06/CCR121519-01]; Blue Cross Blue Shield of Massachusetts, United Way of Mass Bay, The US Potato Board, Stonyfield Farm, and Dole Foods FX Major funding for this research was provided by grant R06/CCR121519-01 from the Centers for Disease Control and Prevention (CDC), Atlanta, GA (Dr. Economos, PI). The review and conduct of the study was overseen by the CDC. Additional unrestricted support was provided by Blue Cross Blue Shield of Massachusetts, United Way of Mass Bay, The US Potato Board, Stonyfield Farm, and Dole Foods. These funders had no study oversight No funders had a role in data collection, management, analysis, or interpretation of the data, nor did they have a role in and preparation, review, or approval of the manuscript NR 30 TC 38 Z9 38 U1 1 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD OCT PY 2013 VL 57 IS 4 BP 322 EP 327 DI 10.1016/j.ypmed.2013.06.001 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 223FC UT WOS:000324789100010 PM 23756187 ER PT J AU Nishiguchi, KM Tearle, RG Liu, YFP Ohd, EC Miyake, N Benaglio, P Harper, S Koskiniemi-Kuendig, H Venturini, G Sharon, D Koenekoop, RK Nakamura, M Kondo, M Ueno, S Yasuma, TR Beckmann, JS Ikegawa, S Matsumoto, N Terasaki, H Berson, EL Katsanis, N Rivolta, C AF Nishiguchi, Koji M. Tearle, Richard G. Liu, Yangfan P. Ohd, Edwin C. Miyake, Noriko Benaglio, Paola Harper, Shyana Koskiniemi-Kuendig, Hanna Venturini, Giulia Sharon, Dror Koenekoop, Robert K. Nakamura, Makoto Kondo, Mineo Ueno, Shinji Yasuma, Tetsuhiro R. Beckmann, Jacques S. Ikegawa, Shiro Matsumoto, Naomichi Terasaki, Hiroko Berson, Eliot L. Katsanis, Nicholas Rivolta, Carlo TI Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE medical genetics; ophthalmology; ciliopathy; retinal blindness ID LEBERS CONGENITAL AMAUROSIS; COPY-NUMBER VARIATIONS; HEARING-LOSS; MUTATION; PROTEIN; ASSOCIATION; RHODOPSIN; APOPTOSIS; ROOTLETIN; THERAPY AB We performed whole genome sequencing in 16 unrelated patients with autosomal recessive retinitis pigmentosa (ARRP), a disease characterized by progressive retinal degeneration and caused by mutations in over 50 genes, in search of pathogenic DNA variants. Eight patients were from North America, whereas eight were Japanese, a population for which ARRP seems to have different genetic drivers. Using a specific workflow, we assessed both the coding and noncoding regions of the human genome, including the evaluation of highly polymorphic SNPs, structural and copy number variations, as well as 69 control genomes sequenced by the same procedures. We detected homozygous or compound heterozygous mutations in 7 genes associated with ARRP (USH2A, RDH12, CNGB1, EYS, PDE6B, DFNB31, and CERKL) in eight patients, three Japanese and five Americans. Fourteen of the 16 mutant alleles identified were previously unknown. Among these, there was a 2.3-kb deletion in USH2A and an inverted duplication of similar to 446 kb in EYS, which would have likely escaped conventional screening techniques or exome sequencing. Moreover, in another Japanese patient, we identified a homozygous frameshift (p.L206fs), absent in more than 2,500 chromosomes from ethnically matched controls, in the ciliary gene NEK2, encoding a serine/threonine-protein kinase. Inactivation of this gene in zebrafish induced retinal photoreceptor defects that were rescued by human NEK2 mRNA. In addition to identifying a previously undescribed ARRP gene, our study highlights the importance of rare structural DNA variations in Mendelian diseases and advocates the need for screening approaches that transcend the analysis of the coding sequences of the human genome. C1 [Nishiguchi, Koji M.; Benaglio, Paola; Koskiniemi-Kuendig, Hanna; Venturini, Giulia; Beckmann, Jacques S.; Rivolta, Carlo] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Nishiguchi, Koji M.; Nakamura, Makoto; Kondo, Mineo; Ueno, Shinji; Yasuma, Tetsuhiro R.; Terasaki, Hiroko] Nagoya Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 4668550, Japan. [Tearle, Richard G.] Complete Genom Inc, Mountain View, CA 94043 USA. [Liu, Yangfan P.; Ohd, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Ohd, Edwin C.] Duke Univ, Dept Neurol, Durham, NC 27710 USA. [Miyake, Noriko; Matsumoto, Naomichi] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004, Japan. [Harper, Shyana; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. [Sharon, Dror] Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, Israel. [Koenekoop, Robert K.] McGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, Canada. [Beckmann, Jacques S.] Univ Lausanne Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Beckmann, Jacques S.] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Ikegawa, Shiro] RIKEN, Ctr Genom Med, Lab Bone & Joint Dis, Tokyo 1088639, Japan. RP Rivolta, C (reprint author), Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. EM carlo.rivolta@unil.ch RI Sharon, Dror/P-4539-2015; Ueno, Shinji/M-5063-2014; Terasaki, Hiroko/M-5054-2014; Ikegawa, Shiro/N-6895-2015; Beckmann, Jacques S /A-9772-2008; OI Sharon, Dror/0000-0002-1789-5811; Ikegawa, Shiro/0000-0003-0316-2147; Beckmann, Jacques S /0000-0002-9741-1900; Rivolta, Carlo/0000-0002-0733-9950; Katsanis, Nicholas/0000-0002-2480-0171 FU Swiss National Science Foundation [310030_138346]; Gebert Ruf Foundation, Switzerland; Foundation Fighting Blindness; National Institutes of Health [DK072301, MH-084018]; Ministry of Health, Labor and Welfare (MHLW) of Japan [23300101, 23300201]; MHLW; Japan Science and Technology Agency; Strategic Research Program for Brain Sciences; Ministry of Education, Culture, Sports, Science and Technology of Japan; Takeda Science Foundation FX We thank Anna M. Siemiatkowska and Frans P. M. Cremers for sharing material from a person with RP, Adriana Ransijn for technical help, as well as Andrea Superti-Furga, and Luisa Bonafe for fruitful suggestions. Data storage was ensured by the Vital-IT Center for high-performance computing of the Swiss Institute of Bioinformatics. This work was supported by the Swiss National Science Foundation (Grant 310030_138346) and the Gebert Ruf Foundation, Switzerland (Rare Diseases-New Technologies Grant) (both to C. R.); a Center Grant from the Foundation Fighting Blindness (to E. L. B.); National Institutes of Health Grants DK072301 and MH-084018 (to N.K.); Ministry of Health, Labor and Welfare (MHLW) of Japan [Grant 23300101 (to S. I. and N. Matsumoto) and Grant 23300201 (to S. I.)]; MHLW, the Japan Science and Technology Agency, and the Strategic Research Program for Brain Sciences (N. Matsumoto); and a Grant-in-Aid for Scientific Research on Innovative Areas (transcription cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Takeda Science Foundation (to N. Matsumoto). NR 35 TC 38 Z9 38 U1 5 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 2013 VL 110 IS 40 BP 16139 EP 16144 DI 10.1073/pnas.1308243110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227II UT WOS:000325105500070 PM 24043777 ER PT J AU Zhang, XY Yao, JK AF Zhang, Xiang Yang Yao, Jeffrey K. TI Oxidative stress and therapeutic implications in psychiatric disorders SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Editorial Material DE Antioxidant defense system; Antioxidant therapy; Bipolar disorders; Major depression; Schizophrenia; Tardive dyskinesia ID TARDIVE-DYSKINESIA; BIPOLAR DISORDER; N-ACETYLCYSTEINE; SCHIZOPHRENIA; INVOLVEMENT; DEPRESSION; RELEVANCE; EPISODES AB Increasing evidence indicates that disturbances of antioxidant defense system and presence of oxidative stress can play a part in a wide range of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and major depression, as well as antipsychotic-induced tardive dyskinesia (TD). Moreover, researchers have embarked on using antioxidant treatment as adjunct therapy for psychiatry disorders. Evidence from clinical, pre-clinical and epidemiological studies suggests that a benefit of using antioxidant compounds should be considered as an adjunctive therapy in these patients. These are some of the main perspectives that are reviewed by four articles in this special section. Overall, there has been growing recognition of the importance of oxidative stress in the pathophysiology of psychiatric disorders and the development of TD. The collection of articles in this special section will contribute to providing more efficacious treatments arising from a better appreciation of the roles of oxidative stress in these psychiatric disorders. (C) 2013 Elsevier Inc. All rights reserved. C1 [Zhang, Xiang Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Zhang, Xiang Yang] Peking Univ, Beijing Hui Long Guan Hosp, Psychiat Res Ctr, Beijing, Peoples R China. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Zhang, XY (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. EM xyzhang@bcm.edu NR 29 TC 25 Z9 27 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD OCT 1 PY 2013 VL 46 BP 197 EP 199 DI 10.1016/j.pnpbp.2013.03.003 PG 3 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 219CA UT WOS:000324480900029 PM 23523744 ER PT J AU Wu, JQ Kosten, TR Zhang, XY AF Wu, Jing Qin Kosten, Thomas R. Zhang, Xiang Yang TI Free radicals, antioxidant defense systems, and schizophrenia SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Antioxidant defense systems; Free radicals; Neuroleptics; Oxidative stress; Schizophrenia; Tardive dyskinesia ID ABNORMAL INVOLUNTARY MOVEMENTS; VITAMIN-E TREATMENT; MEMBRANE-LIPID PEROXIDATION; GENE ALA-9VAL POLYMORPHISM; CT-SCAN ABNORMALITIES; NITRIC-OXIDE SYNTHASE; TARDIVE-DYSKINESIA; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; GLUTATHIONE-PEROXIDASE AB The etiopathogenic mechanisms of schizophrenia are to date unknown, although several hypotheses have been suggested. Accumulating evidence suggests that excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased production of reactive oxygen or decreased antioxidant protection in schizophrenic patients. This review aims to summarize the basic molecular mechanisms of free radical metabolism, the impaired antioxidant defense system and membrane pathology in schizophrenia, their interrelationships with the characteristic clinical symptoms and the implications for antipsychotic treatments. In schizophrenia, there is accumulating evidence of altered antioxidant enzyme activities and increased levels of lipid peroxidation, as well as altered levels of plasma antioxidants. Moreover, free radical-mediated abnormalities may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment with antipsychotic drugs, as well as the development of tardive dyskinesia (TD). Finally, the potential therapeutic strategies implicated by the accumulating data on oxidative stress mechanisms for the treatment of schizophrenia are discussed. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wu, Jing Qin] Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Callaghan, NSW 2308, Australia. [Wu, Jing Qin] Schizophrenia Res Inst, Sydney, NSW, Australia. [Wu, Jing Qin; Kosten, Thomas R.; Zhang, Xiang Yang] Peking Univ, Beijing Hui Long Guan Hosp, Psychiat Res Ctr, Beijing 100096, Peoples R China. [Kosten, Thomas R.; Zhang, Xiang Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX USA. [Kosten, Thomas R.; Zhang, Xiang Yang] Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639]; NHMRC FX This work was funded by the grant from the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. JQW received an NHMRC postdoctoral training fellowship. These sources had no further role in study design, data collection and analysis, decision to publish, or preparation of the article. NR 100 TC 50 Z9 53 U1 10 U2 41 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD OCT 1 PY 2013 VL 46 BP 200 EP 206 DI 10.1016/j.pnpbp.2013.02.015 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 219CA UT WOS:000324480900030 PM 23470289 ER PT J AU Yoo, AJ Chandra, RV Lev, MH AF Yoo, Albert J. Chandra, Ronil V. Lev, Michael H. TI Revascularization Grading: The Devil Is in the Details SO RADIOLOGY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; TRIAL; ALTEPLASE; TIME C1 [Yoo, Albert J.; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. [Chandra, Ronil V.] Monash Med Ctr, Div Diagnost & Intervent Neuroradiol, Melbourne, Vic, Australia. RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost & Intervent Neuroradiol, 55 Fruit St Gray 2, Boston, MA 02114 USA. EM ajyoo@partners.org NR 13 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2013 VL 269 IS 1 BP 6 EP 7 DI 10.1148/radiol.13131281 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 225YH UT WOS:000325000700002 PM 24062558 ER PT J AU Juliano, AF Ginat, DT Moonis, G AF Juliano, Amy F. Ginat, Daniel T. Moonis, Gul TI Imaging Review of the Temporal Bone: Part I. Anatomy and Inflammatory and Neoplastic Processes SO RADIOLOGY LA English DT Review ID ENDOLYMPHATIC SAC TUMORS; HIPPEL-LINDAU-DISEASE; FACIAL-NERVE NEUROMAS; ACOUSTIC NEUROMA; MIDDLE-EAR; COMPUTED-TOMOGRAPHY; PETROUS APEX; GLOMUS TYMPANICUM; SKULL BASE; CEREBELLOPONTINE ANGLE AB From a clinical-radiologic standpoint, there are a limited number of structures and disease entities in the temporal bone with which one must be familiar in order to proficiently interpret a computed tomographic or magnetic resonance imaging study of the temporal bone. It is helpful to examine the region in an organized and systematic fashion, going through the same checklist of key structures each time. This is the first of a two-part review that provides a practical approach to understanding temporal bone anatomy, localizing a pathologic process with a focus on inflammatory and neoplastic processes, identifying pertinent positives and negatives, and formulating a differential diagnosis. (C) RSNA, 2013 C1 [Juliano, Amy F.; Ginat, Daniel T.; Moonis, Gul] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Juliano, AF (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. EM amy_juliano@meei.harvard.edu NR 91 TC 5 Z9 5 U1 1 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 OCT PY 2013 VL 269 IS 1 BP 16 EP 32 DI 10.1148/radiol.13120733 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 225YH UT WOS:000325000700004 ER PT J AU Baker, DA Eudaly, J Smith, CD Obeid, LM Gilkeson, GS AF Baker, DeAnna A. Eudaly, Jackie Smith, Charles D. Obeid, Lina M. Gilkeson, Gary S. TI Impact of sphingosine kinase 2 deficiency on the development of TNF-alpha-induced inflammatory arthritis SO RHEUMATOLOGY INTERNATIONAL LA English DT Article DE Sphingosine kinase 2; Inflammatory arthritis; Sphingolipids; TNF ID FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; DISTINCT ROLES; SPHINGOSINE-1-PHOSPHATE; COLITIS; FTY720; TRAFFICKING; SUPPRESSION; MODULATION; ACTIVATION AB Sphingolipids are components of the plasma membrane whose metabolic manipulation is of interest as a potential therapeutic approach in a number of diseases. Sphingosine kinase 1 (SphK1), the major kinase that phosphorylates sphingosine to sphingosine-1-phosphate (S1P), was previously shown by our group and others to modulate inflammation in murine models of inflammatory arthritis, inflammatory bowel disease and asthma. Sphingosine kinase 2's (SphK2) impact on inflammation is less well known, as variable results were reported depending on the disease model. A specific SphK2 inhibitor inhibited inflammatory arthritis in one model, while siRNA knockdown of SphK2 worsened arthritis in another. We previously demonstrated that SphK1 deficient mice are protected against development of hTNF-alpha-induced arthritis. To investigate the role of SphK2 in TNF-alpha-induced arthritis, we developed SphK2 deficient hTNF-alpha overexpressing mice and separately treated hTNF-alpha mice with ABC294640, a SphK2-specific inhibitor. Our data show that genetic inhibition of SphK2 did not significantly impact the severity or progression of inflammatory arthritis, while pharmacologic inhibition of SphK2 led to significantly more severe arthritis. Compared to vehicle-treated mice, ABC294640 treated mice also had less S1P in whole blood and inflamed joint tissue, although the differences were not significant. ABC294640 treatment did not affect SphK1 activity in the inflamed joint while little SphK2 activity was detected in the joint. We conclude that the differences in the inflammatory phenotype in genetic inhibition versus pharmacologic inhibition of SphK2 can be attributed to the amount of ABC294640 used in the experiments versus the impact of acute inhibition of SphK2 with ABC294640 versus genetically induced life-long SphK2 deficiency. Thus, inhibition of SphK2 appears to be proinflammatory in contrast to the clear anti-inflammatory effects of blocking SphK1. Therapies directed at this sphingosine kinase pathways will need to be specific in their targeting of sphingosine kinases. C1 [Baker, DeAnna A.] Dept Microbiol, Charleston, SC 29425 USA. [Baker, DeAnna A.] Dept Immunol, Charleston, SC 29425 USA. [Eudaly, Jackie; Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA. [Smith, Charles D.] South Carolina Coll Pharm Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Obeid, Lina M.; Gilkeson, Gary S.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Obeid, Lina M.] Dept Biochem, Charleston, SC 29425 USA. [Obeid, Lina M.] Dept Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.; Gilkeson, Gary S.] Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 114 Doughty St,STB 425, Charleston, SC 29425 USA. EM gilkeson@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIAMS NIH HHS [T32 AR050958] NR 22 TC 9 Z9 9 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0172-8172 J9 RHEUMATOL INT JI Rheumatol. Int. PD OCT PY 2013 VL 33 IS 10 BP 2677 EP 2681 DI 10.1007/s00296-012-2493-2 PG 5 WC Rheumatology SC Rheumatology GA 223RC UT WOS:000324824500033 PM 23011090 ER PT J AU Phillips, J Cardile, AP Patterson, TF Lewis, JS AF Phillips, Jason Cardile, Anthony P. Patterson, Thomas F. Lewis, James S., II TI Daptomycin-induced acute eosinophilic pneumonia: Analysis of the current data and illustrative case reports SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Daptomycin; acute eosinophilic pneumonia ID OF-THE-LITERATURE; PULMONARY SURFACTANT; IMPACT AB Acute eosinophilic pneumonia (AEP) is a rare but important complication of daptomycin therapy. We describe 2 cases of daptomycin-associated AEP, compile available data from another 22 published cases, and propose a revised set of diagnostic criteria. C1 [Phillips, Jason; Patterson, Thomas F.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Cardile, Anthony P.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Patterson, Thomas F.] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. RP Cardile, AP (reprint author), Brooke Army Med Ctr, Infect Dis Serv MCHE MDI, 3851 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM anthony.cardile@us.army.mil NR 18 TC 9 Z9 9 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PD OCT PY 2013 VL 45 IS 10 BP 804 EP 808 DI 10.3109/00365548.2013.805427 PG 5 WC Infectious Diseases SC Infectious Diseases GA 220JN UT WOS:000324579200013 PM 23826793 ER PT J AU Antonius, D Bruce, KL Moisa, B Sinclair, SJ Malaspina, D Tremeau, F AF Antonius, Daniel Bruce, Kira L. Moisa, Bethanie Sinclair, Samuel Justin Malaspina, Dolores Tremeau, Fabien TI Familiarity preference in schizophrenia is associated with ambivalent attitudes towards others SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Familiarity preference; Mere exposure effect; Implicit memory; Emotions; Ambivalence; Schizophrenia ID MERE-EXPOSURE; JUDGMENTS; DEFICIT AB Objective: Preferences or attitudes towards others are often shaped through implicit memory processes, and they serve a critical function in our social lives. Preferences driven by implicit familiarity (mere exposure effect) are particularly important when making judgments about others and forming attitudes of liking and social interaction. In schizophrenia, little is known about the effect of familiarity preference on judgments and attitudes toward others. Methods: Subjects included 79 patients with a diagnosis of schizophrenia or schizoaffective disorder and 61 non-patient control subjects. Familiarity preference and trait judgments about others were assessed using a computer task in which neutral faces were rated on positive and negative character traits. "Attractiveness" was rated twice at the beginning and at the end, to measure familiarity preference. Clinical ratings were also obtained. Results: Patients and controls both demonstrated a positive familiarity preference effect. However, the groups differed on the predictive value of familiarity preference for trait judgments. In both groups, the presence of a familiarity preference effect predicted greater positive trait judgments. In patients only, the presence of a familiarity preference effect also predicted, although the correlation was less significant, greater negative trait judgments. Conclusion: The findings are consistent with a preserved familiarity preference effect in individuals with schizophrenia and that the effect is primarily associated with changes in positive attitudes. However, in individuals with schizophrenia this effect is also linked with inferences about negative traits, resulting in ambivalence towards others. This finding may contribute to the impaired social functioning of people with schizophrenia. (C) 2013 Elsevier B.V. All rights reserved. C1 [Antonius, Daniel] SUNY Buffalo, Buffalo, NY 14125 USA. [Antonius, Daniel] Erie Cty Forens Mental Hlth Serv, Buffalo, NY USA. [Antonius, Daniel; Moisa, Bethanie; Malaspina, Dolores; Tremeau, Fabien] NYU, Sch Med, New York, NY USA. [Bruce, Kira L.] SUNY Coll Buffalo, Buffalo, NY 14222 USA. [Sinclair, Samuel Justin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sinclair, Samuel Justin] Harvard Univ, Sch Med, PEaRL, Boston, MA USA. [Tremeau, Fabien] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Antonius, D (reprint author), SUNY Buffalo, Dept Psychiat, Erie Cty Med Ctr, 462 Grider St, Buffalo, NY 14125 USA. EM danielan@buffalo.edu NR 49 TC 5 Z9 5 U1 5 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2013 VL 150 IS 1 BP 229 EP 234 DI 10.1016/j.schres.2013.07.056 PG 6 WC Psychiatry SC Psychiatry GA 216OZ UT WOS:000324294700038 PM 23954145 ER PT J AU Wu, CC Shepard, JAO AF Wu, Carol C. Shepard, Jo-Anne O. TI Tracheal and Airway Neoplasms SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID BRONCHIAL CARCINOID-TUMORS; ADENOID CYSTIC CARCINOMA; NON-HODGKINS-LYMPHOMA; GRANULAR-CELL TUMOR; ENDOBRONCHIAL LIPOMA; COMPUTED-TOMOGRAPHY; CT FINDINGS; MUCOEPIDERMOID CARCINOMA; TRACHEOBRONCHIAL TREE; RADIOLOGIC FINDINGS C1 [Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wu, Carol C.; Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Boston, MA USA. [Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Thorac Imaging & Intervent Div, Boston, MA 02114 USA. RP Wu, CC (reprint author), Massachusetts Gen Hosp, Dept Radiol Thorac Imaging & Intervent, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM carolcwu@gmail.com NR 75 TC 11 Z9 11 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD OCT PY 2013 VL 48 IS 4 BP 354 EP 364 DI 10.1053/j.ro.2013.03.018 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 224NV UT WOS:000324896000010 PM 24034267 ER PT J AU Mao, SH Goodrich, RJ Hauser, R Schrader, SM Chen, Z Krawetz, SA AF Mao, Shihong Goodrich, Robert J. Hauser, Russ Schrader, Steven M. Chen, Zhen Krawetz, Stephen A. TI Evaluation of the effectiveness of semen storage and sperm purification methods for spermatozoa transcript profiling SO SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE LA English DT Article DE mitochondrial RNA; preferentially isolated transcripts; stable transcript pairs ID RNAS; IDENTIFICATION; FERTILIZATION; FERTILE; FRESH AB Different semen storage and sperm purification methods may affect the integrity of isolated spermatozoa! RNA. RNA-Seq was applied to determine whether semen storage methods (pelleted vs. liquefied) and somatic cell lysis buffer (SCLB) vs. PureSperm (PS) purification methods affect the quantity and quality of sperm RNA. The results indicate that the method of semen storage does not markedly impact RNA profiling whereas the choice of purification can yield significant differences. RNA-Seq showed that the majority of mitochondrial and mid-piece associated transcripts were lost after SCLB purification, which indicated that the mid-piece of spermatozoa may have been compromised. In addition, the number of stable transcript pairs from SCLB-samples was less than that from the PS samples. This study supports the view that PS purification better maintains the integrity of spermatozoal RNAs. C1 [Mao, Shihong; Goodrich, Robert J.; Krawetz, Stephen A.] Wayne State Univ, Dept Obstet & Gynecol, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Schrader, Steven M.] NIOSH, Cincinnati, OH 45226 USA. [Schrader, Steven M.; Chen, Zhen] NIH, LIFE Study Team, Bethesda, MD 20892 USA. [Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Krawetz, SA (reprint author), Wayne State Univ, Dept Obstet & Gynecol, 271 CS Mott Ctr,275 E Hancock Ave, Detroit, MI 48201 USA. EM steve@compbio.med.wayne.edu FU Charlotte B. Failing Professorship; Harvard School of Public Health; National Institute of Environmental Health Sciences [ES017285]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [25PM6]; LIFE Study Working Group, Division of Epidemiology, Statistics, and Prevention Research FX The authors declare no conflicts of interest. This work was supported in part by the Charlotte B. Failing Professorship to SAK, a GENI pilot grant to SAK and RH from Harvard School of Public Health; National Institute of Environmental Health Sciences (Grant Number ES017285) to RH and SAK and in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Contract 25PM6 in collaboration with the LIFE Study Working Group, Division of Epidemiology, Statistics, and Prevention Research who provided semen samples for analysis. NR 27 TC 7 Z9 7 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1939-6368 J9 SYST BIOL REPROD MED JI Syst. Biol. Reprod. Med. PD OCT PY 2013 VL 59 IS 5 BP 287 EP 295 DI 10.3109/19396368.2013.817626 PG 9 WC Andrology; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA 221OQ UT WOS:000324668600009 PM 23869956 ER PT J AU Bhatt, SP Dransfield, MT AF Bhatt, Surya P. Dransfield, Mark T. TI Chronic obstructive pulmonary disease and cardiovascular disease SO TRANSLATIONAL RESEARCH LA English DT Review ID CORONARY-HEART-DISEASE; PARTICULATE AIR-POLLUTION; VENTRICULAR DIASTOLIC DYSFUNCTION; 3RD NATIONAL-HEALTH; ANGIOTENSIN-CONVERTING ENZYME; INCREASED ARTERIAL STIFFNESS; NUTRITION EXAMINATION SURVEY; ACUTE MYOCARDIAL-INFARCTION; INTIMA-MEDIA THICKNESS; IMPAIRED LUNG-FUNCTION AB Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung associated with progressive airflow limitation and punctuated by episodes of acute exacerbation. There is growing recognition that the inflammatory state associated with COPD is not confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs. Epidemiologic and mechanistic studies indicate that COPD is associated with a high frequency of coronary artery disease, congestive heart failure and cardiac arrhythmias, independent of shared risk factors. Possible pathways include complex interrelationships between chronic low-grade systemic inflammation and oxidative stress as well as shared risk factors such as age, cigarette smoking, and environmental pollutants. In this review, we provide an overview of the epidemiologic data linking COPD with cardiovascular disease, comment on the interrelationships among COPD, inflammation, and cardiovascular disease, and highlight diagnostic and therapeutic challenges. C1 [Dransfield, Mark T.] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35209 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Dransfield, MT (reprint author), Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35209 USA. EM mdrans99@uab.edu FU National Institutes of Health; Aeris; Astra Zeneca; Boehringer Ingelheim; Boston Scientific; Centocor; Forest; GlaxoSmithKline; Ikaria; Medimmune; Otsuka; Pfizer FX M. T. Dransfield has served as a consultant to Boehringer Ingelheim, GlaxoSmithKline, and Ikaria, and his institution has received research support from the National Institutes of Health, Aeris, Astra Zeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Forest, GlaxoSmithKline, Ikaria, Medimmune, Otsuka, and Pfizer. S. P. Bhatt has no conflicts of interest to declare pertinent to the content of this article. Both authors have read the journal's policy on disclosure of potential conflicts of interest. NR 198 TC 46 Z9 50 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 J9 TRANSL RES JI Transl. Res. PD OCT PY 2013 VL 162 IS 4 BP 237 EP 251 DI 10.1016/j.trsl.2013.05.001 PG 15 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 226RZ UT WOS:000325055000004 PM 23727296 ER PT J AU Flaumenhaft, R AF Flaumenhaft, Robert TI Protein disulfide isomerase as an antithrombotic target SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID MEDIATES PLATELET-AGGREGATION; FORMATION IN-VIVO; THROMBUS FORMATION; PLASMA-MEMBRANE; TISSUE FACTOR; ACTIVATION; INHIBITORS; SURFACE; ASSOCIATION; BACITRACIN AB Protein disulfide disulfide isomerase (PDI) is a ubiquitously expressed oxidoreductase required for proper protein folding. It is highly concentrated in the endoplasmic reticulum, but can also be released into the extracellular environment. Several in vivo thrombosis models have demonstrated that vascular PDI secreted by platelets-and-endothelial cells is essential for normal thrombus formation. Inhibition of extracellular PDI thus represents a potential strategy for antithrombotic therapy. Yet this approach requires the discovery of well-tolerated PDI inhibitors. A recent high-throughput screening identified the commonly ingested flavonoid, quercetin-3-rutinoside, as an inhibitor of PDI. Quercetin-3-rutinoside blocked thrombus formation at concentrations that are commonly ingested as nutritional supplements. The observation that a compound with Generally Recognized As Safe status inhibits PDI and blocks thrombosis in animal models forms a rationale for clinical trials evaluating PDI inhibitors as a new class of antithrombotics. (C) 2013 Elsevier Inc. All rights reserved. C1 [Flaumenhaft, Robert] Harvard Univ, Sch Med, Dept Med, Div Hernostasis & Thrombosis,BIDMC, Boston, MA USA. RP Flaumenhaft, R (reprint author), Beth Israel Deaconess Med Ctr, Ctr Life Sci, Rm 939,3 Blackfan Circle, Boston, MA 02215 USA. EM rflaumen@bidmc.harvard.edu FU NHLBI [U54 HL112302, DA032476, HL87203] FX The work was supported by U54 HL112302, DA032476, and HL87203 from NHLBI. NR 35 TC 15 Z9 16 U1 0 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD OCT PY 2013 VL 23 IS 7 BP 264 EP 268 DI 10.1016/j.tcm.2013.03.001 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 222FS UT WOS:000324717200005 PM 23541171 ER PT J AU Eswara, JR Sharif-Tabrizi, A Sacco, D AF Eswara, Jairam R. Sharif-Tabrizi, Ahmad Sacco, Dianne TI Positive stone culture is associated with a higher rate of sepsis after endourological procedures SO UROLITHIASIS LA English DT Article DE Sepsis; Endoscopy; Percutaneous nephrolithotomy ID PERCUTANEOUS NEPHROLITHOTOMY; URINARY-TRACT; COMPLICATIONS; BACTERIOLOGY AB The purpose of this study was to determine if there is a correlation between urine and/or stone cultures with postoperative sepsis in patients treated for renal and ureteral calculi. Three hundred and twenty-eight consecutive patients who underwent percutaneous nephrolithotomy (PCNL) or ureteroscopy from 2006 to 2009 were identified, all of whom had a stone culture obtained during surgery. All had a preoperative urine culture. Two hundred and seventy-four underwent ureteroscopy and 54 PCNL. All patients had either negative preoperative urine cultures or were given preoperative antibiotics for 1-7 days prior to surgery. Stone fragments were obtained during the procedure and sent for analysis. The primary endpoint was sepsis. Of 328 patients, 3 % (11/328) developed postoperative sepsis. 73 % (8/11) had positive stone cultures, while none had a positive preoperative urine culture. 8 % (8/96) with positive stone cultures and 1 % (3/232) with negative stone cultures developed sepsis (p = 0.003). The stone culture grew the same pathogen as the urine culture obtained on readmission in 64 % (7/11) of the patients, while 9 % (1/11) of preoperative urine cultures correlated with the readmission pathogen (p = 0.02). The pathogen causing infection had a significantly higher correlation with the organism grown on stone culture than the preoperative urine culture. The patients who developed sepsis did so despite preoperative antibiotics, and the pathogen grown on the preoperative urine culture was different from that seen post operatively. These results suggest that stone culture is more informative than preoperative urine culture for determining treatment of postoperative sepsis. C1 [Eswara, Jairam R.; Sharif-Tabrizi, Ahmad; Sacco, Dianne] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Eswara, JR (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM jeswara@partners.org NR 11 TC 16 Z9 18 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2194-7228 J9 UROLITHIASIS JI Urolithiasis PD OCT PY 2013 VL 41 IS 5 BP 411 EP 414 DI 10.1007/s00240-013-0581-8 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 219OA UT WOS:000324515100007 PM 23760449 ER PT J AU Tozburun, S Stahl, CD Hutchens, TC Lagoda, GA Burnett, AL Fried, NM AF Tozburun, Serhat Stahl, Charlotte D. Hutchens, Thomas C. Lagoda, Gwen A. Burnett, Arthur L. Fried, Nathaniel M. TI Continuous-wave Infrared Subsurface Optical Stimulation of the Rat Prostate Cavernous Nerves Using a 1490-nm Diode Laser SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; COHERENCE TOMOGRAPHY; ERECTILE FUNCTION; CAVERMAP; COMPACT; SYSTEM AB OBJECTIVE To optimize the infrared laser wavelength and optical nerve stimulation (ONS) parameters for both deep and rapid subsurface cavernous nerve (CN) stimulation in a rat model, in vivo. MATERIALS AND METHODS A 150-mW, 1490-nm diode laser providing an optical penetration depth (OPD) of 518 mu m in water was operated in continuous-wave mode during stimulation of the CNs in 8 rats for 15 seconds irradiation time through a custom-built, single-mode fiber optic probe capable of producing a collimated, 1-mm diameter laser beam. Successful ONS was judged by an intracavernous pressure response in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 nm and 1550 nm near-infrared diode laser wavelengths. RESULTS Subsurface ONS of the rat CN was successful through fascia layers with a thickness up to 380 mu m using an incident laser power of similar to 50 mW. Intracavernous pressure response times as short as 4.6 +/- 0.2 seconds were recorded using higher laser powers below the nerve damage threshold. CONCLUSION The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper penetration than 1455-nm diode laser and more rapid and efficient nerve stimulation than 1550-nm diode laser. (C) 2013 Elsevier Inc. C1 Univ N Carolina, Dept Phys & Opt Sci, Charlotte, NC 28223 USA. Harvard Univ, Sch Med, Boston, MA USA. [Tozburun, Serhat] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. RP Tozburun, S (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM Tozburun.Serhat@mgh.harvard.edu FU U.S. Department of Defense Prostate Cancer Research Program [PC073709]; U.S. Department of Energy [DE-FG02-06CH11460]; Optics and Photonics Scholarship from SPIE FX This research was supported in part by the U.S. Department of Defense Prostate Cancer Research Program (Grant# PC073709) and the U.S. Department of Energy (Grant# DE-FG02-06CH11460). Serhat Tozburun was supported in part by an Optics and Photonics Scholarship from SPIE. NR 18 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2013 VL 82 IS 4 BP 969 EP 973 DI 10.1016/j.urology.2013.06.031 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 225VV UT WOS:000324994000057 PM 23953608 ER PT J AU Janosek-Albright, K Roghmann, F Noldus, J Sun, M Trinh, QD AF Janosek-Albright, Kirsten Roghmann, Florian Noldus, Joachim Sun, Maxine Trinh, Quoc-Dien TI Re: Schroeck et al.: Differential Adoption of Laser Prostatectomy for Treatment of Benign Prostatic Hyperplasia (Urology 2013;81:1177-1183) SO UROLOGY LA English DT Letter C1 [Janosek-Albright, Kirsten] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Surg,Div Urol, Boston, MA 02115 USA. RP Janosek-Albright, K (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. NR 2 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2013 VL 82 IS 4 BP 980 EP 981 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 225VV UT WOS:000324994000069 PM 24074999 ER PT J AU Oliveira, AP Simabuco, FM Tamura, RE Guerrero, MC Ribeiro, PGG Libermann, TA Zerbini, LF Ventura, AM AF Oliveira, Andressa P. Simabuco, Fernando M. Tamura, Rodrigo E. Guerrero, Manuel C. Ribeiro, Paulo G. G. Libermann, Towia A. Zerbini, Luiz F. Ventura, Armando M. TI Human respiratory syncytial virus N, P and M protein interactions in HEK-293T cells SO VIRUS RESEARCH LA English DT Article DE Human respiratory syncytial virus; Nucleoprotein; Phosphoprotein; Matrix; Protein interaction; Optimized genes ID NUCLEOCAPSID PROTEIN; MATRIX PROTEIN; ACTIN-FILAMENTS; GENE-EXPRESSION; INFECTED-CELLS; F-ACTIN; PHOSPHOPROTEIN; DOMAIN; NUCLEOPROTEIN; REPLICATION AB Characterization of Human Respiratory Syncytial Virus (HRSV) protein interactions with host cell components is crucial to devise antiviral strategies. Viral nucleoprotein, phosphoprotein and matrix protein genes were optimized for human codon usage and cloned into expression vectors. HEK-293T cells were transfected with these vectors, viral proteins were immunoprecipitated, and co-immunoprecipitated cellular proteins were identified through mass spectrometry. Cell proteins identified with higher confidence scores were probed in the immunoprecipitation using specific antibodies. The results indicate that nucleoprotein interacts with arginine methyl-transferase, methylosome protein and Hsp70. Phosphoprotein interacts with Hsp70 and tropomysin, and matrix with tropomysin and nucleophosmin. Additionally, we performed immunoprecipitation of these cellular proteins in cells infected with HRSV, followed by detection of co-immunoprecipitated viral proteins. The results indicate that these interactions also occur in the context of viral infection, and their potential contribution for a HRSV replication model is discussed. (C) 2013 Elsevier B.V. All rights reserved. C1 [Oliveira, Andressa P.; Simabuco, Fernando M.; Tamura, Rodrigo E.; Ribeiro, Paulo G. G.; Ventura, Armando M.] Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, BR-05508900 Sao Paulo, Brazil. [Simabuco, Fernando M.] Univ Estadual Campinas, Fac Ciencias Aplicadas, Sao Paulo, Brazil. [Tamura, Rodrigo E.] Inst Canc Estado Sao Paulo Octavio Frias de Olive, Ctr Invest Translac Oncol CTO, Sao Paulo, Brazil. [Guerrero, Manuel C.; Libermann, Towia A.; Zerbini, Luiz F.] Harvard Univ, Sch Med, BIDMC Genom Ctr, Boston, MA USA. [Zerbini, Luiz F.] Univ Cape Town, ICGEB, ZA-7925 Cape Town, South Africa. [Zerbini, Luiz F.] Univ Cape Town, Div Med Biochem, ZA-7925 Cape Town, South Africa. RP Ventura, AM (reprint author), Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Ave Prof Lineu Prestes 1374, BR-05508900 Sao Paulo, Brazil. EM amventur@usp.br RI tamura, rodrigo/O-9846-2014; Zerbini, Luiz /B-7720-2015; OI tamura, rodrigo/0000-0001-7767-0887; Libermann, Towia/0000-0002-4006-8179 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP [2009/17587-9]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq [477734/2009-0]; FAPESP FX This work was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP (proc. # 2009/17587-9) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq (proc. # 477734/2009-0). A.P.O. has doctoral degree fellowship from FAPESP. NR 49 TC 13 Z9 14 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD OCT PY 2013 VL 177 IS 1 BP 108 EP 112 DI 10.1016/j.virusres.2013.07.010 PG 5 WC Virology SC Virology GA 225PF UT WOS:000324974100013 PM 23892143 ER PT J AU Tirumani, SH Baez, JC Jagannathan, JP Shinagare, AB Ramaiya, NH AF Tirumani, Sree Harsha Baez, Juan C. Jagannathan, Jyothi P. Shinagare, Atul B. Ramaiya, Nikhil H. TI Tumor-bowel fistula: what radiologists should know SO ABDOMINAL IMAGING LA English DT Review DE Tumor-bowel fistula; Fistula; Molecular targeted therapies; CT ID OF-THE-LITERATURE; GASTROINTESTINAL FISTULAS; PNEUMATOSIS-INTESTINALIS; OVARIAN-CARCINOMA; COLORECTAL-CANCER; TARGETED THERAPY; CERVICAL-CANCER; SIGMOID COLON; PERFORATION; BEVACIZUMAB AB Tumor-bowel fistula is an under reported complication of abdomino-pelvic malignancies which may occur spontaneously due to tumor growth or can be associated with cancer treatment. Chemotherapy and radiotherapy are commonly responsible for tumor-bowel fistulas. Molecular targeted therapies are a new class of drugs that can cause tumor fistulization due to their antiangiogenic properties. Clinically, the fistula can be asymptomatic or can result in devastating complications. Imaging helps in the prompt detection of these fistulas and the complications associated with them. Management of tumor-bowel fistula is individualized but often involves discontinuation of the associated treatment. Radiologists should promptly alert the oncology team about the presence of tumor-bowel fistula and any risk factors for its occurrence like pneumatosis or large metastatic deposits close to bowel loops. C1 [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Baez, Juan C.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@part-ners.org NR 24 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD OCT PY 2013 VL 38 IS 5 BP 1014 EP 1023 DI 10.1007/s00261-013-9987-6 PG 10 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 216ZL UT WOS:000324325900011 PM 23455947 ER PT J AU Coopey, SB Tang, R Lei, L Freer, PE Kansal, K Colwell, AS Gadd, MA Specht, MC Austen, WG Smith, BL AF Coopey, Suzanne B. Tang, Rong Lei, Lan Freer, Phoebe E. Kansal, Kari Colwell, Amy S. Gadd, Michele A. Specht, Michelle C. Austen, William G., Jr. Smith, Barbara L. TI Increasing Eligibility for Nipple-Sparing Mastectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID AREOLA COMPLEX; BREAST-CANCER; RECONSTRUCTION; INVOLVEMENT; INCISION; OUTCOMES AB Eligibility for nipple-sparing mastectomy (NSM) varies widely on the basis of patient and tumor factors. Review of patients undergoing NSM from June 2007 to December 2012 at our institution was performed. Patient and tumor characteristics, complications, and recurrences were collected. NSM from 2007 to 2010 and 2011 to 2012 were compared to assess trends in eligibility and outcomes over time. NSM was performed on 645 breasts in 370 patients. Indications were risk reduction in 330 (51.2 %), invasive cancer in 226 (35.0 %), and ductal carcinoma-in situ in 89 (13.8 %) breasts. Fifty-one (13.8 %) patients had positive lymph nodes. Twenty-seven (7.3 %) patients received neoadjuvant chemotherapy. Forty-eight (7.4 %) breasts had prior radiotherapy. Total nipple necrosis occurred in 11 (1.7 %) breasts. Twenty-four (3.7 %) breasts had nipples removed as a result of positive subareolar/nipple margins. At 22 months' mean follow-up, local recurrence occurred in 4 of 156 (2.6 %) breasts operated on for cancer through 2011. No recurrences involved the nipple. NSM performed in 2011-2012 (n = 475) compared to 2007-2010 (n = 170), were more often for cancer, in patients with higher body mass index, and on larger breasts (p < 0.001). There was no significant difference in total nipple necrosis rates between groups. Nipple loss due to positive subareolar/nipple margins was significantly less in 2011-2012 (p = 0.027). Eligibility for NSM has expanded to include women with higher body mass index and larger breasts, with no increase in nipple loss due to ischemia. Rates of positive subareolar margins have decreased over time, even though NSM is being performed more frequently for cancer, suggesting improved patient selection. C1 [Coopey, Suzanne B.; Tang, Rong; Lei, Lan; Kansal, Kari; Gadd, Michele A.; Specht, Michelle C.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Freer, Phoebe E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Colwell, Amy S.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Coopey, SB (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM blsmith1@partners.org OI Freer, Phoebe/0000-0001-6886-7100 NR 20 TC 35 Z9 39 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2013 VL 20 IS 10 BP 3218 EP 3222 DI 10.1245/s10434-013-3152-x PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 211VR UT WOS:000323940000013 PM 23975296 ER PT J AU Schubart, JR Dominici, LS Farnan, M Kelly, TA Manahan, ER Rahman, ER Smith, JS Kass, RB AF Schubart, Jane R. Dominici, Laura S. Farnan, Michelle Kelly, Tricia A. Manahan, Eric R. Rahman, E. Rahkshanda Smith, J. Stanley Kass, Rena B. TI Shared Decision Making in Breast Cancer: National Practice Patterns of Surgeons SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID INFORMED-CONSENT; NECK-SURGERY; INVOLVEMENT; INFORMATION; KNOWLEDGE; PROGRAM; CHOICE; VIDEO; HEAD AB The purpose of this study was to assess national practices of surgeons who treat breast cancer in order to identify opportunities to improve patient education. In June 2012, the membership of the American Society of Breast Surgeons (ASBrS) (n = 2,818) was surveyed via email questionnaire to evaluate their current practice of shared decision making and informed consent for breast cancer patients. A total of 737 members (26 %) responded, including 384 breast surgeons and 306 general surgeons, 13 midlevel providers, and 25 other specialists. It was found that 90 % of surgeons spent more than 30 min meeting with a new cancer patient, and of these, 30 % spent more than an hour. Surgeons who spent more than 1 h face-to-face with a new cancer patient reported higher levels of overall patient knowledge compared with those who spent less (mean = 3.80 vs. 3.64 of 5; p = 0.001). Also, 89 % of respondents reported using educational tools, of whom more than 90 % used written tools. In addition, 65 % of members stated an interest in a free online educational tool if available and indicated a preference for a flexible tool that could be used by the patient alone or with a nurse. While practice patterns may vary, our results reveal that one-third of surgeons spend at least 1 h in consultation with a new breast cancer patient. More time spent translated to a higher perceived patient understanding of their disease and treatment options. Although the majority of surgeons currently use written materials, there was clear support for a free online educational tool. C1 [Schubart, Jane R.] Penn State Univ, Coll Med, Dept Surg, Hershey, PA 17033 USA. [Schubart, Jane R.] Penn State Univ, Coll Med, Dept Med, Hershey, PA USA. [Schubart, Jane R.] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA. [Dominici, Laura S.] Dana Farber, Dept Surg, Boston, MA USA. [Dominici, Laura S.] Brigham & Womens Canc Ctr, Boston, MA USA. [Farnan, Michelle] Penn State Univ, Coll Med, Dept Radiol, Div Breast Imaging, Hershey, PA USA. [Kelly, Tricia A.] St Lukes Canc Care Associates, Allentown, PA USA. [Manahan, Eric R.] Dalton Surg Grp, Dalton, GA USA. [Rahman, E. Rahkshanda] Texas Tech Univ, Hlth Sci Ctr, Dept Surg, Amarillo, TX USA. [Smith, J. Stanley; Kass, Rena B.] Penn State Univ, Coll Med, Dept Surg & Med, Hershey, PA USA. RP Schubart, JR (reprint author), Penn State Univ, Coll Med, Dept Surg, Hershey, PA 17033 USA. EM jschubart@hmc.psu.edu RI chen, zhu/K-5923-2013 NR 25 TC 5 Z9 5 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2013 VL 20 IS 10 BP 3323 EP 3329 DI 10.1245/s10434-013-3112-5 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 211VR UT WOS:000323940000028 PM 23975286 ER PT J AU Schmidt, B Look-Hong, N Maduekwe, UN Chang, K Hong, TS Kwak, EL Lauwers, GY Rattner, DW Mullen, JT Yoon, SS AF Schmidt, Benjamin Look-Hong, Nicole Maduekwe, Ugwuji N. Chang, Kevin Hong, Theodore S. Kwak, Eunice L. Lauwers, Gregory Y. Rattner, David W. Mullen, John T. Yoon, Sam S. TI Noncurative Gastrectomy for Gastric Adenocarcinoma Should only be Performed in Highly Selected Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID TRIAL COMPARING GASTRECTOMY; PALLIATIVE GASTRECTOMY; CANCER PATIENTS; THERAPY; CHEMOTHERAPY; MANAGEMENT; RESECTION; SURVIVAL; OUTCOMES; BENEFIT AB The benefit of surgical resection in patients with incurable gastric adenocarcinoma is controversial. A total of 289 patients who presented with advanced or metastatic gastric cancer from 1995 to 2010 were retrospectively reviewed. Ten patients (3.5 %) required emergent surgery at presentation and were excluded from further analyses. Patients who underwent nonemergent surgery at presentation (n = 110, 38.1 %) received either gastric resection (group A, n = 46, 42 %) or surgery without resection (group B, n = 64, 58 %). Procedures in group A included distal gastrectomy (n = 25, 54 %), total gastrectomy (n = 17, 37 %), and proximal/esophagogastrectomy (n = 4, 9 %). Procedures in group B included laparoscopy (n = 17, 27 %), open exploration (n = 25, 39 %), gastrostomy and/or jejunostomy tube (n = 12, 19 %), and gastrojejunostomy (n = 10, 16 %). Group A required a stay in the intensive care unit or additional invasive procedure significantly more often than group B (15 vs. 2 %, p = 0.009). Four patients in group A (8.7 %) and three patients in group B (4.7 %) died within 30 days of surgery (p = 0.45). When the 110 patients who underwent nonemergent surgery (groups A and B) were compared to nonoperatively managed patients (group C, n = 169, 58 %), median overall survival did not significantly differ (8.6 vs. 9.2 vs. 7.7 months; p > 0.05). Three patients in group B (4.7 %) and three in group C (1.8 %) ultimately required an operation for their primary tumor. Patients with gastric adenocarcinoma who present with advanced or metastatic disease not amenable to curative resection infrequently require emergent surgery. Noncurative resection is associated with significant perioperative morbidity and mortality as well as limited overall survival, and should therefore be performed judiciously. C1 [Schmidt, Benjamin; Look-Hong, Nicole; Maduekwe, Ugwuji N.; Chang, Kevin; Rattner, David W.; Mullen, John T.; Yoon, Sam S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hong, Theodore S.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kwak, Eunice L.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schmidt, B (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM yoons@mskcc.org NR 23 TC 14 Z9 16 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2013 VL 20 IS 11 BP 3512 EP 3518 DI 10.1245/s10434-013-3024-4 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 213MA UT WOS:000324060100024 PM 23765416 ER PT J AU Leece, AK Heidari, P Yokell, DL Mahmood, U AF Leece, Alicia K. Heidari, Pedram Yokell, Daniel L. Mahmood, Umar TI A container closure system that allows for greater recovery of radiolabeled peptide compared to the standard borosilicate glass system SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE Ga-68-DOTATOC; Crystal resin closure system; Peptide adsorption; Recovery AB Objectives: Often peptides used in synthesis of radiopharmaceutical PET tracers are lipophilic and adhere to the walls of container closure systems (CCS) such that costly peptide and product are not fully recoverable after synthesis occurs. This investigation compares a standard United States Pharmacopeia (USP) Type I borosilicate glass CCS to a cyclic polyolefin copolymer Crystal Zenith (CZ) CCS, for Ga-68-chloride and Ga-68-DOTATOC ([Ga-68] Ga-DOTA-D-Phe1-Tyr3-octreotide) retention in the reaction vial after labeling. Methods: (68)Gallium labeling of DOTATOC was conducted by adding Ga-68-chloride, 2 M HEPES (4-(2-hydroxyethyl)piperazine-l-ethanesulfonic acid) or 0.75 M sodium acetate, and 1-30 mu g of DOTATOC into the CZ or glass CCS. The reaction mixture was heated for 15 min and cooled to room temperature. The crude reaction mixture was then withdrawn via syringe, for final processing. The CCS was then assayed using a dose calibrator to determine the amount of retained Ga-68-DOTATOC. Statistical significance was assessed using an unpaired Students t-test. Results: In all experiments (n=72) with various amounts of peptide and different buffering systems, the CZ CCS retained less activity than the glass CCS. Using 2 M HEPES and 15 mu g or 30 mu g of DOTATOC, the CZ CCS retained approximately 10% less of the labeled DOTATOC compared to the glass CCS (p < 0.05). Utilizing either a sodium acetate or a HEPES buffering system with 15 mu g or 30 mu g of DOTATOC, the CZ CCS retained approximately 2.5% less of the total reaction activity compared to the glass CCS (p < 0.05). Product yield was equivalent in glass and CZ CCS under the same reaction conditions. Both the CZ and glass vials showed no retention of Ga-68-chloride. Conclusion: For applications involving the labeling of peptides such as Ga-68-DOTATOC, the CZ CCS compared to the glass CCS, results in an improved recovery of product. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Leece, Alicia K.; Heidari, Pedram; Yokell, Daniel L.; Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NIH [U01 CA143056, U01 CA084301, R01 CA166582]; West Pharmaceutical Services, Inc. FX This work was supported through NIH Grants U01 CA143056, U01 CA084301, and R01 CA166582, and a Grant provided by West Pharmaceutical Services, Inc. NR 10 TC 1 Z9 1 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD OCT PY 2013 VL 80 BP 99 EP 102 DI 10.1016/j.apradiso.2013.06.019 PG 4 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 218QO UT WOS:000324447700017 PM 23860127 ER PT J AU Momen-Heravi, F Balaj, L Alian, S Mantel, PY Halleck, AE Trachtenberg, AJ Soria, CE Oquin, S Bonebreak, CM Saracoglu, E Skog, J Kuo, WP AF Momen-Heravi, Fatemeh Balaj, Leonora Alian, Sara Mantel, Pierre-Yves Halleck, Allison E. Trachtenberg, Alexander J. Soria, Cesar E. Oquin, Shanice Bonebreak, Christina M. Saracoglu, Elif Skog, Johan Kuo, Winston Patrick TI Current methods for the isolation of extracellular vesicles SO BIOLOGICAL CHEMISTRY LA English DT Review DE clinical grade EVs; exosomes; magnetic beads; microvesicles; sedimentation efficiency; ultracentrifugation ID OUTER-MEMBRANE VESICLES; ASCITES-DERIVED EXOSOMES; MENINGOCOCCAL DISEASE; DENDRITIC CELLS; OVARIAN-CANCER; MICROVESICLES MODULATE; BLOOD MICROPARTICLES; CLINICAL-TRIAL; FAS-LIGAND; B-CELL AB Extracellular vesicles (EVs), including microvesicles and exosomes, are nano- to micron-sized vesicles, which may deliver bioactive cargos that include lipids, growth factors and their receptors, proteases, signaling molecules, as well as mRNA and non-coding RNA, released from the cell of origin, to target cells. EVs are released by all cell types and likely induced by mechanisms involved in oncogenic transformation, environmental stimulation, cellular activation, oxidative stress, or death. Ongoing studies investigate the molecular mechanisms and mediators of EVs-based intercellular communication at physiological and oncogenic conditions with the hope of using this information as a possible source for explaining physiological processes in addition to using them as therapeutic targets and disease biomarkers in a variety of diseases. A major limitation in this evolving discipline is the hardship and the lack of standardization for already challenging techniques to isolate EVs. Technical advances have been accomplished in the field of isolation with improving knowledge and emerging novel technologies, including ultracentrifugation, microfluidics, magnetic beads and filtration-based isolation methods. In this review, we will discuss the latest advances in methods of isolation methods and production of clinical grade EVs as well as their advantages and disadvantages, and the justification for their support and the challenges that they encounter. C1 [Kuo, Winston Patrick] Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, Boston, MA 02115 USA. [Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Momen-Heravi, Fatemeh; Halleck, Allison E.; Trachtenberg, Alexander J.] Harvard Univ, Sch Med, Lab Innovat Translat Technol, Boston, MA 02115 USA. [Balaj, Leonora] Massachusetts Gen Hosp, Dept Neurol & Radiol, Charlestown, MA 02129 USA. [Alian, Sara] Harvard Univ, Sch Med, Biopolymers Facil, Boston, MA 02115 USA. [Mantel, Pierre-Yves] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02120 USA. [Soria, Cesar E.] Univ New Mexico, Albuquerque, NM 87131 USA. [Oquin, Shanice] Univ N Texas, Denton, TX 76203 USA. [Bonebreak, Christina M.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Saracoglu, Elif] Istanbul Univ, Fac Dent, TR-34390 Istanbul, Turkey. [Skog, Johan] Exosome Diagnost Inc, New York, NY 10032 USA. RP Kuo, WP (reprint author), Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, Boston, MA 02115 USA. EM wkuo@genetics.med.harvard.edu RI Arumugam, Thirumagal/C-3408-2014; OI Momen-Heravi, Fatemeh/0000-0003-4534-1450 FU Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX This work was conducted, at least in part, through the Harvard Catalyst Laboratory for Innovative Translational Technologies (HC-LITT) with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. NR 69 TC 60 Z9 62 U1 8 U2 113 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD OCT PY 2013 VL 394 IS 10 BP 1253 EP 1262 DI 10.1515/hsz-2013-0141 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 213IS UT WOS:000324050400002 PM 23770532 ER PT J AU Sillivan, SE Whittard, JD Jacobs, MM Ren, YH Mazloom, AR Caputi, FF Horvath, M Keller, E Ma'ayan, A Pan, YX Chiang, LW Hurd, YL AF Sillivan, Stephanie E. Whittard, John D. Jacobs, Michelle M. Ren, Yanhua Mazloom, Amin R. Caputi, Francesca F. Horvath, Monika Keller, Eva Ma'ayan, Avi Pan, Ying-Xian Chiang, Lillian W. Hurd, Yasmin L. TI ELK1 Transcription Factor Linked to Dysregulated Striatal Mu Opioid Receptor Signaling Network and OPRM1 Polymorphism in Human Heroin Abusers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; MAPK; opioid; rat; self-administration; transcriptome ID IN-VIVO; NUCLEAR TRANSLOCATION; BEHAVIORAL-RESPONSES; REWARDING PROPERTIES; SYNAPTIC PLASTICITY; OPIATE ADDICTION; GENE-EXPRESSION; CALCIUM CURRENT; MICE LACKING; PHOSPHORYLATION AB Background: Abuse of heroin and prescription opiate medications has grown to disturbing levels. Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. The striatum is a structure central to reward and habitual behavior and neurobiological changes in this region are thought to underlie the pathophysiology of addiction disorders. Methods: We examined molecular mechanisms related to MOR in postmortem human brain striatal specimens from a homogenous European Caucasian population of heroin abusers and control subjects and in an animal model of heroin self-administration. Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history. Results: A characteristic feature of heroin abusers was decreased expression of MOR and extracellular regulated kinase signaling networks, concomitant with dysregulation of the downstream transcription factor ELK1. Striatal ELK1 in heroin abusers associated with the polymorphism rs2075572 in OPRM1 in a genotype dose-dependent manner and correlated with documented history of heroin use, an effect reproduced in an animal model that emphasizes a direct relationship between repeated heroin exposure and ELK1 dysregulation. A central role of ELK1 was evidenced by an unbiased whole transcriptome microarray that revealed similar to 20% of downregulated genes in human heroin abusers are ELK1 targets. Using chromatin immune precipitation, we confirmed decreased ELK1 promoter occupancy of the target gene Use1. Conclusions: ELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1. C1 [Sillivan, Stephanie E.; Whittard, John D.; Jacobs, Michelle M.; Ren, Yanhua; Caputi, Francesca F.; Hurd, Yasmin L.] Ichan Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Sillivan, Stephanie E.; Whittard, John D.; Jacobs, Michelle M.; Ren, Yanhua; Caputi, Francesca F.; Hurd, Yasmin L.] Ichan Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Sillivan, Stephanie E.; Jacobs, Michelle M.; Ren, Yanhua; Mazloom, Amin R.; Caputi, Francesca F.; Ma'ayan, Avi; Hurd, Yasmin L.] Ichan Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Hurd, Yasmin L.] James J Peters VA Med Ctr, Bronx, NY USA. [Horvath, Monika] Uppsala Univ, Dept Forens Med, Uppsala, Sweden. [Horvath, Monika; Keller, Eva] Semmelweis Univ, Dept Forens Med, H-1085 Budapest, Hungary. [Pan, Ying-Xian] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Pan, Ying-Xian] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program Y XP, New York, NY 10021 USA. [Chiang, Lillian W.] Purdue Pharma LP, Cranbury, NJ USA. RP Hurd, YL (reprint author), Ichan Sch Med Mt Sinai, Dept Psychiat, 1 Gustave L Levy Pl,Box 1065, New York, NY 10029 USA. EM yasmin.hurd@mssm.edu FU National Institute on Drug Abuse [DA015446, DA013997, T32DA007135, ETT/098/2009]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This work was funded by grants from the National Institute on Drug Abuse DA015446 (YLH), DA013997 (Y-XP), and T32DA007135 (MMJ), as well as Grant ETT/098/2009 (EK). The study was also supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. NR 80 TC 8 Z9 8 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2013 VL 74 IS 7 BP 511 EP 519 DI 10.1016/j.biopsych.2013.04.012 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 216UJ UT WOS:000324310000008 PM 23702428 ER PT J AU Kil, KE Zhang, ZD Jokivarsi, K Gong, CY Choi, JK Kura, S Brownell, AL AF Kil, Kun-Eek Zhang, Zhaoda Jokivarsi, Kimmo Gong, Chunyu Choi, Ji-Kyung Kura, Sreekanth Brownell, Anna-Liisa TI Radiosynthesis of N-(4-chloro-3-[C-11]methoxyphenyl)-2-picolinamide ([C-11]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu(4)) SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE [C-11] ML128; PET; Metabotropic glutamate receptor subtype 4 (mGlu(4)); Positive allosteric modulator ID PARKINSONS-DISEASE; ALLOSTERIC MODULATION; BASAL GANGLIA; LOCALIZATION; MGLUR4; GLUTAMATE-RECEPTOR-4; RAT; CNS AB N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu(4) positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu(4) PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu(4) expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([C-11]3) as a PET radiotracer for mGlu(4), and characterized its biological properties in Sprague Dawley rats. [C-11]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [C-11]CH3I. Total synthesis time was 38 +/- 2.2 min (n = 7) from the end of bombardment to the formulation. The radioligand [C-11] 3 was obtained in 27.7 +/- 5.3% (n = 5) decay corrected radiochemical yield based on the radioactivity of [C-11]CO2. The radiochemical purity of [C-11]3 was >99%. Specific activity was 188.7 +/- 88.8 GBq/mol (n = 4) at the end of synthesis (EOS). PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu(4) modulator (4) to investigate specificity and 3 studies blocking with an mGlu(5) modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [C-11]3 (peak activity between 1-3 min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu(4) modulator 4 showed 22-28% decrease of [C-11]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu(5). Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu(4), in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Kil, Kun-Eek; Zhang, Zhaoda; Jokivarsi, Kimmo; Gong, Chunyu; Choi, Ji-Kyung; Kura, Sreekanth; Brownell, Anna-Liisa] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. EM abrownell@partners.org FU NCRR NIH HHS [S10 RR023385, S10 RR023452, S10 RR026666, S10 RR029495]; NIBIB NIH HHS [R01 EB012864]; NIMH NIH HHS [R01 MH091684] NR 27 TC 8 Z9 8 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT 1 PY 2013 VL 21 IS 19 BP 5955 EP 5962 DI 10.1016/j.bmc.2013.07.046 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 213HN UT WOS:000324046600003 PM 23978356 ER PT J AU Peterson, YK Cameron, RB Wills, LP Trager, RE Lindsey, CC Beeson, CC Schnellmann, RG AF Peterson, Yuri K. Cameron, Robert B. Wills, Lauren P. Trager, Richard E. Lindsey, Chris C. Beeson, Craig C. Schnellmann, Rick G. TI beta(2)-Adrenoceptor agonists in the regulation of mitochondrial biogenesis SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Adrenoceptor; Biogenesis; Mitochondria; Pharmacophore; Chemical similarity; Clustering; Renal ID NEURAL STEM-CELLS; FUNCTIONAL SELECTIVITY; RECEPTOR LIGANDS; CAMP; BETA(2); CULTURE; GLUCONEOGENESIS; AVAILABILITY; ADRENOCEPTOR; METABOLISM AB The stimulation of mitochondrial biogenesis (MB) via cell surface G-protein coupled receptors is a promising strategy for cell repair and regeneration. Here we report the specificity and chemical rationale of a panel of beta(2)-adrenoceptor agonists with regards to MB. Using primary cultures of renal cells, a diverse panel of beta(2)-adrenoceptor agonists elicited three distinct phenotypes: full MB, partial MB, and non-MB. Full MB compounds had efficacy in the low nanomolar range and represent two chemical scaffolds containing three distinct chemical clusters. Interestingly, the MB phenotype did not correlate with reported receptor affinity or chemical similarity. Chemical clusters were then subjected to pharmacophore modeling creating two models with unique and distinct features, consisting of five conserved amongst full MB compounds were identified. The two discrete pharmacophore models were coalesced into a consensus pharmacophore with four unique features elucidating the spatial and chemical characteristics required to stimulate MB. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Peterson, Yuri K.; Cameron, Robert B.; Wills, Lauren P.; Trager, Richard E.; Lindsey, Chris C.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health [T32 CA119945-04, F32 ES020103-01, ES012878, DK071997, GM084147]; Biomedical LaboratoryResearch and Development Program of the Department of Veterans Affairs [1BX000851]; [T32 GM08716] FX R.B.C. is funded by T32 GM08716. L.P.W. is funded by the National Institutes of Health grant T32 CA119945-04 and F32 ES020103-01. R.G.S. is funded by the National Institutes of Health grants ES012878, DK071997 and GM084147, and the Biomedical LaboratoryResearch and Development Program of the Department of Veterans Affairs [1BX000851]. The authors also thank Kathryn Appleton and Louis Luttrell for thoughtful discussions and Gyda Beeson for technical assistance. NR 39 TC 8 Z9 8 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 1 PY 2013 VL 23 IS 19 BP 5376 EP 5381 DI 10.1016/j.bmcl.2013.07.052 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 216RX UT WOS:000324302800023 PM 23954364 ER PT J AU Mendoza, TR Zhao, FM Cleeland, CS Wagner, LI Patrick-Miller, LJ Fisch, MJ AF Mendoza, Tito R. Zhao, Fengmin Cleeland, Charles S. Wagner, Lynne I. Patrick-Miller, Linda J. Fisch, Michael J. TI The Validity and Utility of the M. D. Anderson Symptom Inventory in Patients With Breast Cancer: Evidence From the Symptom Outcomes and Practice Patterns Data From the Eastern Cooperative Oncology Group SO CLINICAL BREAST CANCER LA English DT Article DE Eastern Cooperative Oncology Group; M. D. Anderson Symptom Inventory; Patient-reported outcome; Symptom assessment; Validation ID QUALITY-OF-LIFE; CLINICAL-TRIALS; FUNCTIONAL ASSESSMENT; REPORTED OUTCOMES; CHEMOTHERAPY; SEVERITY; THERAPY; WOMEN; VALIDATION; INSTRUMENT AB The M. D. Anderson Symptom Inventory assesses the severity and impact of multiple symptoms related to cancer and its treatment. Psychometric analysis of data from a national multicenter study of 1544 patients with breast cancer showed the M. D. Anderson Symptom Inventory to be a valid, reliable, sensitive symptom-assessment instrument that can enhance descriptive and clinical studies of symptom status in this patient population. Background: The M. D. Anderson Symptom Inventory (MDASI) is a psychometrically validated patient-reported outcome measurement that assesses the severity and impact of multiple symptoms related to cancer and its treatment. With the MDASI, patients rate 13 common "core" symptoms and 6 items that reflect symptom interference with functioning. Several MDASI modules (core symptom and interference items plus additional symptoms specific to a particular cancer type or treatment modality) have been developed. Although the original MDASI validation study encompassed various cancer types, the instrument's psychometric properties have not been examined in a homogenous sample of patients with breast cancer in a national multicenter study. Materials and Methods: We performed a secondary analysis of data from an Eastern Cooperative Oncology Group study to establish the reliability, validity, and sensitivity of the MDASI in a large sample of patients with breast cancer (n = 1544), 78% of whom were receiving treatment. The instrument was administered twice, approximately 1 month apart. Results: Internal consistency and test-retest reliability were adequate, with Cronbach alpha values >= 0.85 and intraclass correlations >= 0.76 for all subscales. Known-group validity was evaluated by using performance status, tumor response, and disease stage. Sensitivity to change in patient-reported quality of life was established. Conclusion: The MDASI is a valid, reliable, and sensitive symptom-assessment instrument that can enhance descriptive and clinical studies of symptom status in patients with breast cancer. Future studies might include cognitive debriefing and qualitative interviews to identify additional disease-specific items for inclusion in a MDASI breast cancer module. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mendoza, Tito R.; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wagner, Lynne I.] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA. [Wagner, Lynne I.] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Patrick-Miller, Linda J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Patrick-Miller, Linda J.] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. RP Mendoza, TR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 1450, Houston, TX 77030 USA. EM tmendoza@mdanderson.org FU National Cancer Institute of the National Institutes of Health [U10 CA37403, U10 CA17145, U10 CA107868]; MD Anderson Cancer Center [P30 CA016672]; [R01 CA026582] FX We thank Jeanie F. Woodruff, ELS, for editorial assistance and the ECOG Symptom Outcomes and Practice Patterns study for the data. This study was supported in part by grants to ECOG from the National Cancer Institute of the National Institutes of Health, including U10 CA37403, U10 CA17145, and U10 CA107868. Additional support comes from R01 CA026582 to C. S. C and MD Anderson Cancer Center Support Grant P30 CA016672 to R. A. DePinho. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 39 TC 5 Z9 6 U1 3 U2 5 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD OCT PY 2013 VL 13 IS 5 BP 325 EP 334 DI 10.1016/j.clbc.2013.02.014 PG 10 WC Oncology SC Oncology GA 217FE UT WOS:000324341600004 PM 23816985 ER PT J AU Fogh, S Kachnic, LA Goldberg, SI Taghian, AG Powell, SN Hirsch, AE AF Fogh, Shannon Kachnic, Lisa A. Goldberg, Saveli I. Taghian, Alphonse G. Powell, Simon N. Hirsch, Ariel E. TI Localized Therapy for Male Breast Cancer: Functional Advantages With Comparable Outcomes Using Breast Conservation SO CLINICAL BREAST CANCER LA English DT Article DE Breast-conserving surgery; Male breast cancer; Radiation therapy ID 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; MASTECTOMY; CARCINOMA; EXPERIENCE; MANAGEMENT; MEN AB A retrospective analysis was undertaken of male patients with breast cancer. Musculoskeletal functionality and cosmesis (tissue fibrosis, arm edema and range of motion) and treatment outcome (local-regional control, disease-free and overall survival) were evaluated. Actuarial overall 1-year 'fair-poor' documented tissue fibrosis, arm edema and decreased range of motion rates were 13%, 23% and 27% for patients receiving MRM, 25%, 0% and 50% for patients who underwent TSM, and 13%, 0% and 0% for those undergoing BCS. Breast conservation therapy may be considered a reasonable local treatment option for male patients presenting with breast cancer as it may offer cosmetic and functional and cosmetic advantages over mastectomy, with comparable rates of local control, and disease-free and overall survival. Background: Male breast cancer (MBC) accounts for approximately 1% of all breast cancers. Given the rarity of this disease, treatment of MBC generally follows the same principles as treatment of female breast cancer. However, the traditional surgical approach for MBC is modified radical mastectomy (MRM) or total simple mastectomy (TSM) instead of breast conservation surgery (BCS). The purpose of this study was to examine the feasibility of BCS as an alternative to mastectomy for MBC with respect to musculoskeletal functionality and treatment outcome. Patients and Methods: A retrospective analysis was undertaken of all male patients with breast cancer who presented to Massachusetts General Hospital or Boston Medical Center for localized therapy from 1990 to 2003. Musculoskeletal functionality (tissue fibrosis, arm edema, and range of motion) and treatment outcome (local-regional control, disease-free survival, and overall survival) were evaluated. Functional/cosmetic outcomes were assessed by multidisciplinary review of patient follow-up visits and were scored as either "good-excellent" or "fair-poor" to account for subjectivity between different clinicians. Results: Forty-two patients in total were identified to undergo localized treatment. Thirty patients (71%) received MRM, 4 (10%) had TSM, and 8 (19%) underwent BCS. Actuarial overall 1-year fair-poor documented tissue fibrosis, arm edema, and decreased range of motion rates were 13%, 23%, and 27% for patients receiving MRM; 25%, 0%, and 50% for patients who underwent TSM; and 13%, 0%, and 0% for those undergoing BCS, respectively. Overall survival and disease-free survival were not statistically different between the groups. Conclusions: These data suggest that breast conservation therapy may be considered a reasonable local treatment option for male patients presenting with breast cancer because it may offer functional advantages over mastectomy with comparable rates of local control and disease-free survival and overall survival. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fogh, Shannon] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Kachnic, Lisa A.; Goldberg, Saveli I.; Taghian, Alphonse G.; Hirsch, Ariel E.] Massachusetts Gen Hosp, Dept Radiat Oncol 5, Boston, MA 02114 USA. [Powell, Simon N.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Fogh, S (reprint author), Univ Calif San Francisco, 505 Parnassus Ave,L-08 Box 0226, San Francisco, CA 94143 USA. EM foghse@radonc.ucsf.edu NR 21 TC 2 Z9 2 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD OCT PY 2013 VL 13 IS 5 BP 344 EP 349 DI 10.1016/j.clbc.2013.05.004 PG 6 WC Oncology SC Oncology GA 217FE UT WOS:000324341600006 PM 23891587 ER PT J AU Leaf, DE Waikar, SS Wolf, M Cremers, S Bhan, I Stern, L AF Leaf, David E. Waikar, Sushrut S. Wolf, Myles Cremers, Serge Bhan, Ishir Stern, Leonard TI Dysregulated mineral metabolism in patients with acute kidney injury and risk of adverse outcomes SO CLINICAL ENDOCRINOLOGY LA English DT Article ID VITAMIN-D DEFICIENCY; INTENSIVE-CARE-UNIT; ACUTE-RENAL-FAILURE; D-BINDING PROTEIN; HEMODIALYSIS-PATIENTS; INCREASED MORTALITY; DISEASE; SERUM; PLASMA; RECEPTOR AB Objective Numerous studies have evaluated the prevalence and importance of vitamin D deficiency among patients with chronic kidney disease and end-stage renal disease; however, little is known about vitamin D levels in acute kidney injury (AKI). We evaluated the association between vitamin D metabolites and clinical outcomes among patients with AKI. Design Prospective cohort study. Patients A total of 30 participants with AKI and 30 controls from general hospital wards and intensive care units at a tertiary care hospital were recruited for the study. Measurements Plasma levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], 24R,25-dihydroxyvitamin D-3, vitamin D binding protein (VDBP) and fibroblast growth factor 23 (FGF23) were measured within 24 hours of AKI onset and 5 days later. Bioavailable 25(OH)D and 1,25(OH)(2)D levels, defined as the sum of free- and albumin-bound 25(OH)D and 1,25(OH)(2)D, were estimated using equations. Results Compared to controls, participants with AKI had lower levels of 1,25(OH)(2)D [17 (10-22) vs 25 (15-35) pg/ml, P = 0.01], lower levels of VDBP [23 (15-31) vs 29 (25-36) mg/dl, P = 0.003] and similar levels of bioavailable 25(OH)D and 1,25(OH)(2)D at enrolment. Levels of bioavailable 25(OH)D were inversely associated with severity of sepsis in the overall sample (P < 0.001). Among participants with AKI, bioavailable 25(OH)D, but not other vitamin D metabolites, was significantly associated with mortality after adjusting for age and serum creatinine (adjusted odds ratio per 1 SD ln [bioavailable 25(OH)D]=0.16, 95% confidence interval = 0.03-0.85). Conclusions Bioavailable 25(OH)D could have a role as a biomarker or mediator of adverse outcomes among patients with established AKI. C1 [Leaf, David E.; Stern, Leonard] Columbia Univ, Med Ctr, Div Nephrol, New York, NY USA. [Leaf, David E.; Waikar, Sushrut S.] Brigham & Womens Hosp, Div Renal Med, Boston, MA 02115 USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Cremers, Serge] Columbia Univ, Med Ctr, Div Endocrinol, New York, NY USA. [Bhan, Ishir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Leaf, DE (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02115 USA. EM deleaf@partners.org FU Columbia University Clinical and Translational Science Award from the National Center for Research Resources/National Institutes of Health [UL1RR024156]; National Institutes of Health [R01DK076116, R01DK081374] FX This work was supported by a generous donation from the Nortillo Foundation, Columbia University Clinical and Translational Science Award Grant UL1RR024156 from the National Center for Research Resources/National Institutes of Health, and National Institutes of Health Grants R01DK076116 (to M.W.) and R01DK081374 (to M.W.). NR 33 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 2013 VL 79 IS 4 BP 491 EP 498 DI 10.1111/cen.12172 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 211SY UT WOS:000323932200007 PM 23414198 ER PT J AU Nummenmaa, A Stenroos, M Ilmoniemi, RJ Okada, YC Hamalainen, MS Raij, T AF Nummenmaa, Aapo Stenroos, Matti Ilmoniemi, Risto J. Okada, Yoshio C. Haemaelaeinen, Matti S. Raij, Tommi TI Comparison of spherical and realistically shaped boundary element head models for transcranial magnetic stimulation navigation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Transcranial magnetic stimulation; Image guided navigation; Electromagnetic modeling; Boundary element method ID INHOMOGENEOUS VOLUME CONDUCTOR; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; DIFFUSION TENSOR MRI; ELECTRIC-FIELD; BRAIN-TISSUE; POTENTIALS; ANISOTROPY; ACCURACY; SYSTEM AB Objective: MRI-guided real-time transcranial magnetic stimulation (TMS) navigators that apply electromagnetic modeling have improved the utility of TMS. However, their accuracy and speed depends on the assumed volume conductor geometry. Spherical models found in present navigators are computationally fast but may be inaccurate in some areas. Realistically shaped boundary-element models (BEMs) could increase accuracy at a moderate computational cost, but it is unknown which model features have the largest influence on accuracy. Thus, we compared different types of spherical models and BEMs. Methods: Globally and locally fitted spherical models and different BEMs with either one or three compartments and with different skull-to-brain conductivity ratios (1/1-1/80) were compared against a reference BEM. Results: The one-compartment BEM at inner skull surface was almost as accurate as the reference BEM. Skull/brain conductivity ratio in the range 1/10-1/80 had only a minor influence. BEMs were superior to spherical models especially in frontal and temporal areas (up to 20 mm localization and 40% intensity improvement); in motor cortex all models provided similar results. Conclusions: One-compartment BEMs offer a good balance between accuracy and computational cost. Significance: Realistically shaped BEMs may increase TMS navigation accuracy in several brain areas, such as in prefrontal regions often targeted in clinical applications. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Nummenmaa, Aapo; Haemaelaeinen, Matti S.; Raij, Tommi] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Nummenmaa, Aapo; Stenroos, Matti; Ilmoniemi, Risto J.] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Stenroos, Matti] Med Res Council Cognit & Brain Sci Unit, Cambridge, England. [Okada, Yoshio C.] Moment Technol LLC, Boston, MA 02129 USA. [Okada, Yoshio C.] Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp Boston, Boston, MA 02115 USA. RP Nummenmaa, A (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM nummenma@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Ilmoniemi, Risto/E-9704-2012 OI Ilmoniemi, Risto/0000-0002-3340-2618 FU Academy of Finland [127624, 252223]; National Institutes of health (NIH) [R01-NS048279, R01-NS037462, R01-HD040712, R01-MH083744,, R21-DC010060]; NIBIB [R01-EB009048]; NIH Shared Instrumentation [S10-RR024794]; Harvard Clinical and Translational Science Center [NCRR-NIH UL1-RR025758]; NIH Center for Functional Neuroimaging Technologies (CFNT) [NIBIB P41-EB015896] FX This work has been supported by Academy of Finland project number 127624 (AN), decision number 252223 (RJI), National Institutes of health (NIH) grants R01-NS048279, R01-NS037462, R01-HD040712, R01-MH083744, and R21-DC010060 (TR), NIBIB R01-EB009048 (MSH), NIH Shared Instrumentation Grant S10-RR024794, Harvard Clinical and Translational Science Center (Harvard Catalyst; NCRR-NIH UL1-RR025758), and The NIH Center for Functional Neuroimaging Technologies (CFNT) NIBIB P41-EB015896. The content is solely the responsibility of the authors and does not necessarily represent the official views of the CFNT, NCRR, or NIH. NR 60 TC 15 Z9 15 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2013 VL 124 IS 10 BP 1995 EP 2007 DI 10.1016/j.clinph.2013.04.019 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 219TB UT WOS:000324531400013 PM 23890512 ER PT J AU Jensen, MP Sherlin, LH Askew, RL Fregni, F Witkop, G Gianas, A Howe, JD Hakimian, S AF Jensen, Mark P. Sherlin, Leslie H. Askew, Robert L. Fregni, Felipe Witkop, Gregory Gianas, Ann Howe, Jon D. Hakimian, Shahin TI Effects of non-pharmacological pain treatments on brain states SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Spinal cord injury; Chronic pain; Electroencephalography; Brain states; Non-pharmacological treatments ID DIRECT-CURRENT STIMULATION; SPINAL-CORD-INJURY; EEG BIOFEEDBACK; CLINICAL PAIN; HYPNOSIS; MEDITATION; CORTEX; RELAXATION; INTENSITY; ATTENTION AB Objective: To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram-(EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations. Methods: 30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], neurofeedback, and a control sham tDCS procedure). Results: Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain. Conclusions: Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments. Significance: The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Jensen, Mark P.; Askew, Robert L.; Gianas, Ann] Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Seattle, WA 98104 USA. [Sherlin, Leslie H.] Southwest Coll Naturopath Med, Dept Mind Body Med, Tempe, AZ USA. [Sherlin, Leslie H.] Nova Tech EEG, Mesa, AZ USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat,Spaulding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Harvard Spinal Cord Injury Model Syst, Spaulding Rehabil Hosp, Boston, MA USA. [Witkop, Gregory] Univ Washington, Appl Phys Lab, Seattle, WA 98105 USA. [Howe, Jon D.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Hakimian, Shahin] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Jensen, MP (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Box 359612,325 9th Ave, Seattle, WA 98104 USA. EM mjensen@uw.edu RI Howe, Jon/J-5063-2012; OI Howe, Jon/0000-0003-1271-1312; Askew, Robert/0000-0002-9579-2279 FU National Institutes of Health [R21 HD058049]; National Institute of Child Health and Human Development; National Center for Medical Rehabilitation Research FX This research was supported by grant number R21 HD058049 from the National Institutes of Health, National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research. NR 63 TC 18 Z9 19 U1 1 U2 37 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2013 VL 124 IS 10 BP 2016 EP 2024 DI 10.1016/j.clinph.2013.04.009 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 219TB UT WOS:000324531400015 PM 23706958 ER PT J AU Bot, AGJ Anderson, JA Neuhaus, V Ring, D AF Bot, Arjan G. J. Anderson, Jade A. Neuhaus, Valentin Ring, David TI Factors Associated With Survey Response in Hand Surgery Research SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MAIL SURVEYS; FOLLOW-UP; NONRESPONSE BIAS; COST-EFFECTIVENESS; KNEE ARTHROPLASTY; RANDOMIZED-TRIAL; HEALTH; QUESTIONNAIRE; PAIN; VALIDATION AB A low response rate is believed to decrease the validity of survey studies. Factors associated with nonresponse to surveys are poorly characterized in orthopaedic research. This study addressed whether (1) psychologic factors; (2) demographics; (3) illness-related factors; and (4) pain are predictors of a lower likelihood of a patient returning a mailed survey. One hundred four adult, new or return patients completed questionnaires including the Pain Catastrophizing Scale, Patient Health Questionnaire-9 depression scale, Short Health Anxiety Index, demographics, and a pain scale (0-10) during a routine visit to a hand and upper extremity surgeon. Of these patients, 38% had undergone surgery and the remainder was seen for various other conditions. Six months after their visit, patients were mailed the DASH questionnaire and a scale to rate their satisfaction with the visit (0-10). Bivariate analysis and logistic regression were used to determine risk factors for being a nonresponder to the followup of this study. The cohort consisted of 57 women and 47 men with a mean age of 51 years with various diagnoses. Thirty-five patients (34%) returned the questionnaire. Responders were satisfied with their visit (mean satisfaction, 8.7) and had a DASH score of 9.6. Compared with patients who returned the questionnaires, nonresponders had higher pain catastrophizing scores, were younger, more frequently male, and had more pain at enrollment. In logistic regression, male sex (odds ratio [OR], 2.6), pain (OR, 1.3), and younger age (OR, 1.03) were associated with not returning the questionnaire. Survey studies should be interpreted in light of the fact that patients who do not return questionnaires in a hand surgery practice differ from patients who do return them. Hand surgery studies that rely on questionnaire evaluation remote from study enrollment should include tactics to improve the response of younger, male patients with more pain. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Bot, Arjan G. J.; Neuhaus, Valentin; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. [Anderson, Jade A.] Boston Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02118 USA. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 FU Skeletal Dynamics (Miami, FL, USA); Wright Medical (Arlington, TN, USA); Biomet (Warsaw, IN, USA); Dutch orthopaedic travel grant; Anna Fonds Travel grant (Oestgeest, the Netherlands); VSBfonds (Utrecht, the Netherlands); Prins Bernhard Cultuurfonds/Banning-de Jong fonds (Amsterdam, the Netherlands); Gottfried und Julia Bangerter-Rhyner-Stiftung (Bern, Switzerland) FX One of the authors (DR) received a study-specific grant from Skeletal Dynamics (Miami, FL, USA). One of the authors (DR) certifies that he has or may receive payments or benefits, during the study period, an amount of USD 10,000-100,000; an amount less than USD 10,000 from Wright Medical (Arlington, TN, USA), an amount less than USD 10,000 from Skeletal Dynamics (Miami, FL, USA), and an amount less than USD 10,000 from Biomet (Warsaw, IN, USA). One of the authors (AGJB) received a Dutch orthopaedic travel grant, Anna Fonds Travel grant (Oestgeest, the Netherlands); a nonmedical study grant, VSBfonds (Utrecht, the Netherlands); and a nonmedical study grant for excellent Dutch students, Prins Bernhard Cultuurfonds/Banning-de Jong fonds (Amsterdam, the Netherlands). One of the authors (VN) received a grant from Gottfried und Julia Bangerter-Rhyner-Stiftung (Bern, Switzerland). NR 33 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2013 VL 471 IS 10 BP 3237 EP 3242 DI 10.1007/s11999-013-3126-0 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 216YU UT WOS:000324323900030 PM 23801062 ER PT J AU Menendez, ME Neuhaus, V Bot, AGJ Vrahas, MS Ring, D AF Menendez, Mariano E. Neuhaus, Valentin Bot, Arjan G. J. Vrahas, Mark S. Ring, David TI Do Psychiatric Comorbidities Influence Inpatient Death, Adverse Events, and Discharge After Lower Extremity Fractures? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; MEDICARE BENEFICIARIES; GLOBAL PREVALENCE; KNEE ARTHROPLASTY; OLDER-ADULTS; PRIMARY-CARE; RISK-FACTORS; DEPRESSION; MORTALITY AB Psychiatric comorbidity is known to contribute to illness (the state of feeling unwell/unable to rely on one's body) and increased use of healthcare resources, but the effect on inpatient outcomes in fracture care is relatively unexplored. Our primary null hypothesis is that a concomitant diagnosis of depression, anxiety, dementia, or schizophrenia is not associated with (1) discharge to another care facility rather than home after lower extremity fractures. Secondary study questions address the associations between psychiatric comorbidity and (2) longer inpatient stay and inpatient (3) adverse events; (4) blood transfusion; and (5) mortality after lower extremity fractures. Using the National Hospital Discharge Survey database, we analyzed a total estimated number of 10,669,449 patients with lower limb fractures from 1990 to 2007. Sixty-four percent were women, and the mean +/- A SD age was 67 +/- A 22 years. The prevalence in the study population was 3.2% for depression, 1.6% for anxiety, 0.6% for schizophrenia, and 2.9% for dementia. A discharge diagnosis of psychiatric comorbidity was associated with a lower rate of discharge to home after accounting for an association with greater medical comorbidity (schizophrenia: odds ratio [OR], 5.6, 95% confidence interval [CI], 5.5-5.8; dementia: OR, 1.3, 95% CI, 1.2-1.3; depression: OR, 1.2, 95% CI, 1.2-1.3; anxiety: OR, 1.04, 95% CI, 1.02-1.06). Hospital stay was longer for patients with schizophrenia and dementia but shorter in patients with depression or anxiety compared with patients without any mental disorders. Schizophrenia was associated with more in-hospital adverse events and depression and anxiety with fewer events. A diagnosis of depression was associated with blood transfusion. Psychiatric comorbidity was not associated with a higher risk of in-hospital death. Optimal inpatient management of patients with lower extremity fractures should account for the influence of psychiatric comorbidities, dementia and schizophrenia in particular. C1 [Menendez, Mariano E.; Neuhaus, Valentin; Bot, Arjan G. J.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. [Vrahas, Mark S.] Massachusetts Gen Hosp, Orthopaed Trauma Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 FU Gottfried und Julia Bangerter-Rhyner-Stiftung (Bern, Switzerland); Prins Bernhard Cultuurfonds/Banning-de Jong Fonds (Amsterdam, The Netherlands); VSBfonds (Utrecht, The Netherlands); Anna Fonds (Oegstgeest, The Netherlands) FX One of the authors (VN) certifies that he has received, during the study period, funding from Gottfried und Julia Bangerter-Rhyner-Stiftung (Bern, Switzerland). One of the authors (AGJB) certifies that he has received, during the study period, funding from Prins Bernhard Cultuurfonds/Banning-de Jong Fonds (Amsterdam, The Netherlands), VSBfonds (Utrecht, The Netherlands), and Anna Fonds (Oegstgeest, The Netherlands). NR 45 TC 8 Z9 8 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2013 VL 471 IS 10 BP 3336 EP 3348 DI 10.1007/s11999-013-3138-9 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 216YU UT WOS:000324323900047 PM 23813242 ER PT J AU Varghese, FP Cummings, DL AF Varghese, Femina P. Cummings, Devon L. TI Introduction: Why Apply Vocational Psychology to Criminal Justice Populations? SO COUNSELING PSYCHOLOGIST LA English DT Editorial Material DE vocational; career; work; social justice; offender; criminal ID PRISONER REENTRY; CORRECTIONAL PSYCHOLOGISTS; CAREER-DEVELOPMENT; CLINICAL-PRACTICE; PUBLIC-POLICY; WORK; OFFENDERS; EMPLOYMENT; CRIME; EXPECTANCIES AB The criminal justice population has experienced exponential growth in recent decades. Yet, counseling and vocational psychology has not kept pace in addressing the vocational needs of this population. A recent literature search in counseling and vocational journals found that in the last quarter century, only 14 articles have been published that focus on this topic. Among these, even fewer are focused on developing effective vocational interventions for this population. The articles in this major contribution endeavor to begin filling this gap by (a) demonstrating the need and applicability for applying counseling and vocational psychology in developing vocational interventions for the criminal justice population, (b) providing an example and initial empirical findings of a vocational intervention used with this population, and (c) informing readers of best practices in interdisciplinary research for theoretical integration to work with this population. C1 [Varghese, Femina P.] Univ Cent Arkansas, Counseling Psychol Program, Conway, AR 72035 USA. [Cummings, Devon L.] Univ Cent Arkansas, Conway, AR 72035 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Varghese, FP (reprint author), Univ Cent Arkansas, Dept Psychol & Counseling, 201 Donaghey Ave, Conway, AR 72035 USA. EM fvarghese@uca.edu NR 106 TC 2 Z9 2 U1 9 U2 35 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0011-0000 J9 COUNS PSYCHOL JI Couns. Psychol. PD OCT PY 2013 VL 41 IS 7 BP 961 EP 989 DI 10.1177/0011000012459363 PG 29 WC Psychology, Applied SC Psychology GA 211HD UT WOS:000323896200002 ER PT J AU Mitsiades, CS Chen-Kiang, S AF Mitsiades, Constantine S. Chen-Kiang, Selina TI Immunomodulation as a therapeutic strategy in the treatment of multiple myeloma SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Multiple myeloma; Immunomodulation; Anticancer; Thalidomide; Lenalidomide; Pomalidomide ID LONG-TERM SURVIVAL; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; DENDRITIC CELLS; T-CELLS; THALIDOMIDE ANALOGS; DRUG-RESISTANCE; CLINICAL-COURSE; TNF-ALPHA; IN-VIVO AB Growth and survival of multiple myeloma (MM) cells depend on intrinsic, cell-autonomous parameters, such as the genetic lesions harboured by the MM cells, as well as extracellular, cell-non-autonomous factors, including the interaction between MM cells and bone-marrow stromal cells and the suppression of the host's anticancer immune responses. Thalidomide and the immunomodulatory agents lenalidomide and pomalidomide have pleiotropic effects on MM cells and their microenvironment, including promotion of direct mechanisms of MM-cell apoptosis, as well as indirect mechanisms mediated by perturbation of cell adhesion, modulation of cytokine production, and inhibition of tumor-associated angiogenesis. The immunomodulatory properties of these agents are mediated by effects on T-cell proliferation and function, stimulation of natural killer cells, and inhibition of regulatory T cells. Thalidomide and lenalidomide have established roles in the treatment of patients with newly diagnosed MM and those with relapsed/refractory disease. Pomalidomide is currently being evaluated in clinical trials, and preliminary clinical data suggest that it is active in patients with MM that is refractory to lenalidomide and bortezomib treatment. This article provides an overview of the current and potential future roles of immunomodulation in the management of MM, and how improved anticancer immune responses may improve treatment outcomes. (C) 2013 Published by Elsevier Ireland Ltd. C1 [Mitsiades, Constantine S.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Dept Med Oncol, Boston, MA 02115 USA. [Chen-Kiang, Selina] Cornell Univ, Dept Pathol, Weill Med Coll, New York, NY 10065 USA. RP Chen-Kiang, S (reprint author), Cornell Univ, Dept Pathol, Weill Med Coll, 1300 York Ave, New York, NY 10065 USA. EM constantine_mitsiades@dfci.harvard.edu; sckiang@med.cornell.edu FU Celgene Corporation FX We thank Shanthi Jayawardena, PhD, and Eva Polk, PhD and Grace Tjon, PhD (Excerpta Medica), for linguistic improvement of the manuscript. Editorial support in the preparation of this manuscript was funded by Celgene Corporation. The authors were fully responsible for all content and editorial decisions for this manuscript. NR 73 TC 8 Z9 8 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD OCT 1 PY 2013 VL 88 SU 1 BP S5 EP S13 DI 10.1016/j.critrevonc.2013.05.014 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 218TI UT WOS:000324455000002 PM 23806982 ER EF