FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Walton, DS Nagao, K Yeung, HH Kane, SA AF Walton, David S. Nagao, Karina Yeung, Helen H. Kane, Steven A. TI Late-Recognized Primary Congenital Glaucoma SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article ID PRIMARY INFANTILE GLAUCOMA; CHILDHOOD GLAUCOMA; UPDATE AB Purpose: To describe a cohort of children with late-recognized primary congenital glaucoma (LRPCG), including age of presentation, age-related diagnostic signs, clinical abnormalities, and results of glaucoma surgery. Methods: The medical records of 31 patients (49 eyes) with PCG recognized after 1 year of age were reviewed retrospectively. Patients were confirmed to have PCG based on their increased intraocular pressure (IOP), anterior segment abnormalities including findings on gonioscopy, and the absence of other causes of childhood glaucoma. The outcome of glaucoma surgery was reviewed and success measured by assessment of the relative control of IOP, occurrence of significant complications, and need for additional glaucoma surgery. Results: Average age at diagnosis of glaucoma was 4.7 years (36% diagnosed at > 4 years of age). The most common initial diagnostic signs were corneal enlargement (46%, average age of 2.0 years), photophobia (20%, average age of 3.3 years), and suspected poor visual acuity (32%, average age of 9.9 years). Corneal cloudiness was not an initial sign for any patient. Haab's striae were present in 60% of the affected 49 eyes. Gonioscopy findings were abnormal in 82%, but the ciliary body band was seen in 81% and the scleral spur was visible in 47%. Sixty-one goniotomy procedures were performed for 39 eyes with overall success in 95% (37 eyes) and complete success in 65% (27 eyes). The final visual acuity was 20/200 or worse in 31% (15 eyes) and 20/40 or better in 60% (29 eyes). Conclusions: An awareness of and familiarity with the subtle diagnostic signs of LRPCG can enable its differentiation from primary juvenile glaucoma and contribute to earlier recognition and treatment. Glaucoma surgery is often required for LRPCG and goniosurgery is the recommended initial procedure. C1 [Walton, David S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Nagao, Karina] COE RIO, Rio De Janeiro, Brazil. [Yeung, Helen H.] New York Eye & Ear Infirm, Dept Ophthalmol, New York, NY USA. [Kane, Steven A.] Columbia Univ, Dept Ophthalmol, Edward S Harkness Eye Inst, Coll Phys & Surg, New York, NY 10027 USA. RP Walton, DS (reprint author), 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA. EM walton.blackeye@gmail.com FU Children's Glaucoma Foundation, Boston, Massachusetts FX Supported by the Children's Glaucoma Foundation, Boston, Massachusetts. NR 15 TC 4 Z9 4 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD JUL-AUG PY 2013 VL 50 IS 4 BP 234 EP 238 DI 10.3928/01913913-20130423-02 PG 5 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 204BE UT WOS:000323338700008 PM 23614468 ER PT J AU Song, Y Cho, G Suh, JY Lee, CK Kim, YR Kim, YJ Kim, JK AF Song, Youngkyu Cho, Gyunggoo Suh, Ji-Yeon Lee, Chang Kyung Kim, Young Ro Kim, Yoon Jae Kim, Jeong Kon TI Dynamic Contrast-Enhanced MRI for Monitoring Antiangiogenic Treatment: Determination of Accurate and Reliable Perfusion Parameters in a Longitudinal Study of a Mouse Xenograft Model SO KOREAN JOURNAL OF RADIOLOGY LA English DT Article DE Angiogenesis; Dynamic contrast enhanced MR; Two compartment model; Tumor perfusion ID MAGNETIC-RESONANCE; MICROVESSEL DENSITY; TUMOR ANGIOGENESIS; KINETIC-PARAMETERS; CANCER; BREAST; CARCINOMA; THERAPY; SU11248; TRACER AB Objective: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice. Materials and Methods: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (K-ep, K-el, and A(H) from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated. Results: Tumor growth rate was found to be 129% +/- 28 in control group, -33% +/- 11 in four mice with sunitinib-treatment (tumor regression) and 47% +/- 15 in four with sunitinib-treatment (growth retardation). K-ep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, K-ep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, K-ep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate. Conclusion: K-ep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment. C1 [Song, Youngkyu; Cho, Gyunggoo; Suh, Ji-Yeon; Lee, Chang Kyung; Kim, Jeong Kon] Korea Basic Sci Inst, Div Magnet Resonance, Cheongwon 363883, South Korea. [Suh, Ji-Yeon; Lee, Chang Kyung; Kim, Jeong Kon] Univ Ulsan, Coll Med, Res Inst Radiol, Dept Radiol, Seoul 138736, South Korea. [Kim, Yoon Jae] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul 138736, South Korea. [Kim, Young Ro] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kim, JK (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol,Res Inst Radiol, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea. EM kim.jeongkon@gmail.com FU Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science of Technology [2011-0028826, 2010-0025731]; Korea Basic Science Institute [T3222K] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science of Technology (grant number 2011-0028826 and 2010-0025731), and by a grant from Korea Basic Science Institute (T3222K). NR 25 TC 2 Z9 2 U1 0 U2 4 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JUL-AUG PY 2013 VL 14 IS 4 BP 589 EP 596 DI 10.3348/kjr.2013.14.4.589 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 201KF UT WOS:000323139800006 PM 23901316 ER PT J AU Chu, SH Karri, S Ma, YB Feng, DF Li, ZQ AF Chu, Sheng-Hua Karri, Surya Ma, Yan-Bin Feng, Dong-Fu Li, Zhi-Qiang TI In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles SO NEURO-ONCOLOGY LA English DT Article DE rain metastatic tumor; glioblastoma; hydroxyapatite nanoparticles; irradiation; radiosensitization ID DOUBLE-STRAND BREAKS; GLIOMA; CELLS; INHIBITOR; RADIATION; SLC22A18; BONE; GLIOBLASTOMA; TEMOZOLOMIDE; PROGRESSION AB Background. Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of radiosensitivity induced by nano-HAPs. Methods. In vitro radiosensitization of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using gamma H2AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor radiosensitivity was investigated in a subcutaneous and an orthotopic model. Results. Nano-HAPs enhanced each cell line's radiosensitivity when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the G(2) cell cycle checkpoint. The number of gamma H2AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation. Conclusions. These results show that nano-HAPs can enhance the radiosensitivity of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe. C1 [Chu, Sheng-Hua; Ma, Yan-Bin; Feng, Dong-Fu] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 3, Sch Med, Dept Neurosurg, Shanghai 201900, Peoples R China. [Chu, Sheng-Hua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Karri, Surya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Li, Zhi-Qiang] Wuhan Univ, Zhongnan Hosp, Dept Neurosurg, Wuhan 430072, Peoples R China. RP Chu, SH (reprint author), Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 3, Sch Med, Dept Neurosurg, Shanghai 201900, Peoples R China. EM shenghuachu@126.com FU Innovation Program of Shanghai Municipal Education Commission [12YZ046]; Natural Science Foundation of China [30901535]; New One Hundred Person Project of Shanghai Jiao Tong University of School of Medicine [10XBR01] FX This work was supported in part by grants from the Innovation Program of Shanghai Municipal Education Commission (12YZ046), the Natural Science Foundation of China (30901535), and the New One Hundred Person Project of Shanghai Jiao Tong University of School of Medicine (10XBR01). NR 35 TC 5 Z9 5 U1 3 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2013 VL 15 IS 7 BP 880 EP 890 DI 10.1093/neuonc/not030 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 173RE UT WOS:000321095800010 PM 23519742 ER PT J AU Norden, AD Lesser, GJ Drappatz, J Ligon, KL Hammond, SN Lee, EQ Reardon, DR Fadul, CE Plotkin, SR Batchelor, TT Zhu, JJ Beroukhim, R Muzikansky, A Doherty, L Lafrankie, D Smith, K Tafoya, V Lis, R Stack, EC Rosenfeld, MR Wen, PY AF Norden, Andrew D. Lesser, Glenn J. Drappatz, Jan Ligon, Keith L. Hammond, Samantha N. Lee, Eudocia Q. Reardon, David R. Fadul, Camilo E. Plotkin, Scott R. Batchelor, Tracy T. Zhu, Jay-Jiguang Beroukhim, Rameen Muzikansky, Alona Doherty, Lisa Lafrankie, Debra Smith, Katrina Tafoya, Vida Lis, Rosina Stack, Edward C. Rosenfeld, Myrna R. Wen, Patrick Y. TI Phase 2 study of dose-intense temozolomide in recurrent glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE dose-intense temozolomide; MGMT promoter methylation; recurrent glioblastoma ID DNA MISMATCH REPAIR; TUMOR PROGRESSION; MALIGNANT GLIOMA; II TRIAL; RESISTANCE; SCHEDULES; THERAPY; MSH6 AB Background. Among patients with glioblastoma (GBM) who progress on standard temozolomide, the optimal therapy is unknown. Resistance to temozolomide is partially mediated by O-6-methylguanine-DNA methyltransferase (MGMT). Because MGMT may be depleted by prolonged temozolomide administration, dose-intense schedules may overcome resistance. Methods. This was a multicenter, phase 2, single-arm study of temozolomide (75-100 mg/m(2)/day) for 21 days of each 28-day cycle. Patients had GBM in first recurrence after standard therapy. The primary end point was 6-month progression-free survival (PFS6). Results. Fifty-eight participants were accrued, 3 of whom were ineligible for analysis; one withdrew before response assessment. There were 33 men (61%), with a median age of 57 years (range, 25-79 years) and a median Karnofsky performance score of 90 (range, 60100). Of 47 patients with MGMT methylation results, 36 (65%) had methylated tumors. There were 7 (13%) partial responses, and PFS6 was only 11%. Response and PFS did not depend on MGMT status; MSH2, MLH1, or ERCC1 expression; the number of prior temozolomide cycles; or the time off temozolomide. Treatment was well tolerated, with limited grade 3 neutropenia (n = 2) or thrombocytopenia (n = 2). Conclusions. Dose-intense temozolomide on this schedule is safe in recurrent GBM. However, efficacy is marginal and predictive biomarkers are needed. C1 [Norden, Andrew D.; Hammond, Samantha N.; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Smith, Katrina; Tafoya, Vida; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Norden, Andrew D.; Lee, Eudocia Q.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Lesser, Glenn J.] Wake Forest Univ, Baptist Med Ctr, Sect Hematol & Oncol, Winston Salem, NC 27109 USA. [Drappatz, Jan] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Pittsburgh, PA USA. [Ligon, Keith L.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Neurooncol Program, Lebanon, NH 03766 USA. [Plotkin, Scott R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Pappas Ctr Neurooncol, Boston, MA USA. [Zhu, Jay-Jiguang] Univ Texas Hlth Sci Ctr Houston, Mischer Neurosci Inst, Mem Hermann Hosp, Vivian L Smith Dept Neurosurg, Houston, TX 77030 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Ligon, Keith L.; Lis, Rosina; Stack, Edward C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.; Lis, Rosina; Stack, Edward C.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Rosenfeld, Myrna R.] Univ Penn, Dept Neurol, Div Neurooncol, Philadelphia, PA 19104 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org OI Rosenfeld, Myrna/0000-0001-5095-2534 FU Merck FX This work was supported by Merck. NR 23 TC 29 Z9 31 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2013 VL 15 IS 7 BP 930 EP 935 DI 10.1093/neuonc/not040 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 173RE UT WOS:000321095800014 PM 23553268 ER PT J AU Ratai, EM Zhang, Z Snyder, BS Boxerman, JL Safriel, Y McKinstry, RC Bokstein, F Gilbert, MR Sorensen, AG Barboriak, DP AF Ratai, Eva-Maria Zhang, Zheng Snyder, Bradley S. Boxerman, Jerrold L. Safriel, Yair McKinstry, Robert C. Bokstein, Felix Gilbert, Mark R. Sorensen, A. Gregory Barboriak, Daniel P. TI Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677 SO NEURO-ONCOLOGY LA English DT Article DE anti-angiogenic therapy; bevacizumab; Cho; glioblastoma; magnetic resonance spectroscopy; NAA ID BRAIN-TUMORS; N-ACETYLASPARTATE; MR SPECTROSCOPY; PHASE-II; BEVACIZUMAB; MULTIFORME; MULTICENTER; SURVIVAL; GLIOMA; PROGRESSION AB Background. The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy. Methods. Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of N-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values. Results. NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival. Conclusion. Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment. C1 [Ratai, Eva-Maria; Sorensen, A. Gregory] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Neuroradiol Div,AA Martino, Charlestown, MA 02129 USA. [Zhang, Zheng; Snyder, Bradley S.] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Boxerman, Jerrold L.] Brown Univ, Alpert Med Sch, Dept Diagnost Imaging, Providence, RI 02912 USA. [Safriel, Yair] Univ S Florida, Radiol Associates Clearwater, Clearwater, FL USA. [McKinstry, Robert C.] Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA. [Bokstein, Felix] Univ Texas MD Anderson Canc Ctr, Tel Aviv Sourasky Med Ctr, Neurooncol Serv, Houston, TX 77030 USA. [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Ratai, EM (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Neuroradiol Div,AA Martino, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM ratai@nmr.mgh.harvard.edu RI Zhang, Zheng/J-2388-2014; Gilbert, Mark/J-7494-2016 OI Zhang, Zheng/0000-0003-2497-0362; Gilbert, Mark/0000-0003-2556-9722 FU National Cancer Institute [U01 CA079778, U01 CA080098] FX This work was supported by the National Cancer Institute to ACRIN (grants U01 CA079778 and U01 CA080098). NR 35 TC 21 Z9 23 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2013 VL 15 IS 7 BP 936 EP 944 DI 10.1093/neuonc/not044 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 173RE UT WOS:000321095800015 PM 23645534 ER PT J AU Boxerman, JL Zhang, Z Safriel, Y Larvie, M Snyder, BS Jain, R Chi, TL Sorensen, AG Gilbert, MR Barboriak, DP AF Boxerman, Jerrold L. Zhang, Zheng Safriel, Yair Larvie, Mykol Snyder, Bradley S. Jain, Rajan Chi, T. Linda Sorensen, A. Gregory Gilbert, Mark R. Barboriak, Daniel P. TI Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab and irinotecan; imaging biomarker; overall survival; progression; recurrent glioblastoma ID HIGH-GRADE GLIOMAS; PHASE-II TRIAL; RESPONSE ASSESSMENT; MALIGNANT GLIOMA; CONCOMITANT RADIOCHEMOTHERAPY; NEUROONCOLOGY CRITERIA; ADJUVANT TEMOZOLOMIDE; PSEUDO-PROGRESSION; PLUS IRINOTECAN; PSEUDOPROGRESSION AB Background. RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS). Methods. Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression. Results. Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively). Conclusion. Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM. C1 [Boxerman, Jerrold L.] Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI 02903 USA. [Boxerman, Jerrold L.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Zhang, Zheng; Snyder, Bradley S.] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Safriel, Yair] Univ S Florida, Pharmascan Clin Trials & Radiol Associates Clearw, Clearwater, FL USA. [Larvie, Mykol] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jain, Rajan] Henry Ford Hosp, Dept Radiol, Detroit, MI 48202 USA. [Jain, Rajan] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [Chi, T. Linda] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Boxerman, JL (reprint author), Rhode Isl Hosp, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA. EM jboxerman@lifespan.org RI Zhang, Zheng/J-2388-2014; Gilbert, Mark/J-7494-2016 OI Zhang, Zheng/0000-0003-2497-0362; Gilbert, Mark/0000-0003-2556-9722 FU National Cancer Institute [U01-CA080098, U01-CA079778] FX ACRIN receives funding from the National Cancer Institute through grants U01-CA080098 and U01-CA079778. NR 51 TC 18 Z9 18 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2013 VL 15 IS 7 BP 945 EP 954 DI 10.1093/neuonc/not049 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 173RE UT WOS:000321095800016 PM 23788270 ER PT J AU Aizer, AA Sethi, RV Hedley-Whyte, ET Ebb, D Tarbell, NJ Yock, TI MacDonald, SM AF Aizer, Ayal A. Sethi, Roshan V. Hedley-Whyte, E. Tessa Ebb, David Tarbell, Nancy J. Yock, Torunn I. MacDonald, Shannon M. TI Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications SO NEURO-ONCOLOGY LA English DT Article DE bifocal; germ cell; multiple midline; NGGCT; nongerminomatous ID PINEAL REGION TUMORS; GERMINOMA; IRRADIATION; CHEMOTHERAPY; EXPERIENCE; MANAGEMENT; OUTCOMES; SURGERY; HYDROCEPHALUS; RADIATION AB Background. Patients presenting with synchronous bifocal intracranial tumors (masses in the pineal and neurohypophyseal region), detectable human chorionic gonadotropin (hCG) levels (5-100 mIU/mL), and normal alpha feto-protein (AFP) levels (<= 10 ng/mL) are often diagnosed empirically with pure germinoma. In such scenarios, pathologic confirmation is often deferred, given that bifocal nongerminomatous germ cell tumors (NGGCTs) are considered rare and because available literature and research protocols support such an approach. Wesought to characterize the association between bifocal intracranial tumors and NGGCT histology. Methods. Seventy-one patients treated for intracranial germ cell tumors at Massachusetts General Hospital in 1998-2012 were identified. Patients presenting with synchronous bifocal disease were selected for further review. Results. Of the 71 patients presenting with intracranial germ cell tumors, 14 (19.7%) had synchronous bifocal disease. Of these 14 patients, 7 (50.0%) had germinoma, 3 (21.4%) had NGGCT, and 4 (28.6%) had hCG levels <200 mIU/mL and normal AFP levels and were treated without pathologic confirmation. Of the 3 patients with confirmed bifocal NGGCT, 2 had detectable hCG levels with AFP <10 ng/mL and 1 patient had a detectable hCG level with a modest elevation in AFP. Conclusions. NGGCTs should be considered in the differential diagnosis for patients presenting with bifocal intracranial tumors. Given differences in the management of germinomas and NGGCTs, clinicians should strongly consider a biopsy in patients presenting with bifocal masses and normal or modestly elevated biomarkers. Misclassification of such cases as germinomas could result in undertreatment and a possible increased risk for recurrence. C1 [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Sethi, Roshan V.] Harvard Univ, Sch Med, Boston, MA USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol & Neuropathol, Boston, MA USA. [Ebb, David] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. [Tarbell, Nancy J.; Yock, Torunn I.; MacDonald, Shannon M.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Suite 107,55 Fruit St, Boston, MA 02114 USA. EM smacdonald@partners.org NR 29 TC 10 Z9 11 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2013 VL 15 IS 7 BP 955 EP 960 DI 10.1093/neuonc/not050 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 173RE UT WOS:000321095800017 PM 23640532 ER PT J AU Birdsill, AC Carlsson, CM Willette, AA Okonkwo, OC Johnson, SC Xu, GF Oh, JM Gallagher, CL Koscik, RL Jonaitis, EM Hermann, BP LaRue, A Rowley, HA Asthana, S Sager, MA Bendlin, BB AF Birdsill, Alex C. Carlsson, Cynthia M. Willette, Auriel A. Okonkwo, Ozioma C. Johnson, Sterling C. Xu, Guofan Oh, Jennifer M. Gallagher, Catherine L. Koscik, Rebecca L. Jonaitis, Erin M. Hermann, Bruce P. LaRue, Asenath Rowley, Howard A. Asthana, Sanjay Sager, Mark A. Bendlin, Barbara B. TI Low Cerebral Blood Flow is Associated with Lower Memory Function in Metabolic Syndrome SO OBESITY LA English DT Article ID PRECLINICAL ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; PERFUSION MRI; DEMENTIA; RISK; INVERSION; DECLINE; PET AB Background: Metabolic syndrome (MetS)-a cluster of cardiovascular risk factors-is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed. Design and Methods: Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose. Results: Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF. Conclusions: The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population. C1 [Birdsill, Alex C.; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Johnson, Sterling C.; Xu, Guofan; Oh, Jennifer M.; Asthana, Sanjay; Bendlin, Barbara B.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Birdsill, Alex C.; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Johnson, Sterling C.; Xu, Guofan; Oh, Jennifer M.; Gallagher, Catherine L.; Rowley, Howard A.; Asthana, Sanjay; Sager, Mark A.; Bendlin, Barbara B.] Univ Wisconsin, Dept Med, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Willette, Auriel A.] NIA, Baltimore, MD 21224 USA. [Gallagher, Catherine L.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. [Gallagher, Catherine L.] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. [Koscik, Rebecca L.; Jonaitis, Erin M.; Hermann, Bruce P.; LaRue, Asenath; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Bendlin, BB (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU Alzheimer's Association [NIRG-09-132626]; National Institute on Aging [R01 AG027161, ADRC P50 AG033514]; National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award [1UL1RR025011]; University of Wisconsin Institute for Clinical and Translational Research FX This project was supported by the Alzheimer's Association, NIRG-09-132626, and in part by the National Institute on Aging (R01 AG027161 [MAS], ADRC P50 AG033514 [SA]), and the University of Wisconsin Institute for Clinical and Translational Research, funded through a National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award, 1UL1RR025011. The project was also facilitated by the facilities and resources at the Geriatric Research, Education, and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. GRECC MS # 2012-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 26 Z9 27 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2013 VL 21 IS 7 BP 1313 EP 1320 DI 10.1002/oby.20170 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 204FV UT WOS:000323351400002 PM 23687103 ER PT J AU Bove, RM Brick, DJ Healy, BC Mancuso, SM Gerweck, AV Bredella, MA Sherman, JC Miller, KK AF Bove, R. M. Brick, D. J. Healy, B. C. Mancuso, S. M. Gerweck, A. V. Bredella, M. A. Sherman, J. C. Miller, K. K. TI Metabolic and Endocrine Correlates of Cognitive Function in Healthy Young Women SO OBESITY LA English DT Article ID BODY-MASS INDEX; GROWTH-FACTOR-I; INSULIN SENSITIVITY; WORKING-MEMORY; OBESE-PATIENTS; OLDER WOMEN; VITAMIN-D; PERFORMANCE; ASSOCIATION; ACTIVATION AB Objective: Obesity has been associated with cognitive decline in longitudinal studies of older individuals. We hypothesized that the cognitive sequelae of obesity may be detectable in the reproductive years. In addition, we explored the hypothesis that these associations may be mediated by the hormonal milieu. Design and Methods: Of 49 young healthy lean and overweight women aged 20-45, we investigated the association between performance on a battery of cognitive tests, body composition parameters [body mass index, total fat, abdominal (visceral, subcutaneous, and total) adipose tissue, and muscle], and hormone levels (insulin, adiponectin, leptin, insulin-like growth factor 1 (IGF-1), estrogen, testosterone, and vitamin D). Results: We found a significant negative association between both visceral adiposity and muscle, and performance in the domain of verbal learning and memory, after controlling for age and education. Other body composition parameters showed similar trends (0.05 < P < 0.10). Additionally, the degree of insulin resistance was negatively associated with executive function domain. None of the associations between the other hormones examined (adipokines, IGF-1, gonadal hormones, and vitamin D) and cognitive function were significant. Conclusion: These preliminary findings suggest a possible association between obesity and cognitive function in healthy young women of reproductive age. More research is warranted into the potential modulatory effect of insulin resistance on this association. C1 [Bove, R. M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Bove, R. M.; Brick, D. J.; Mancuso, S. M.; Gerweck, A. V.; Bredella, M. A.; Sherman, J. C.; Miller, K. K.] Harvard Univ, Sch Med, Boston, MA USA. [Brick, D. J.; Gerweck, A. V.; Miller, K. K.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Mancuso, S. M.; Sherman, J. C.] Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. [Bredella, M. A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Bove, RM (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM rbove@partners.org FU [R01 HL-077674]; [K23 RR-23090]; [UL1 RR-025758] FX This research was supported by the R01 HL-077674, K23 RR-23090, and UL1 RR-025758. NR 40 TC 12 Z9 12 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2013 VL 21 IS 7 BP 1343 EP 1349 DI 10.1002/oby.20212 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 204FV UT WOS:000323351400006 PM 23671055 ER PT J AU Boeke, CE Mantzoros, CS Hughes, MD Rifas-Shiman, SL Villamor, E Zera, CA Gillman, MW AF Boeke, Caroline E. Mantzoros, Christos S. Hughes, Michael D. Rifas-Shiman, Sheryl L. Villamor, Eduardo Zera, Chloe A. Gillman, Matthew W. TI Differential Associations of Leptin with Adiposity Across Early Childhood SO OBESITY LA English DT Article ID HYPOTHALAMIC FEEDING CIRCUITS; CORD BLOOD LEPTIN; WEIGHT-GAIN; RECOMBINANT LEPTIN; HUMAN PHYSIOLOGY; BODY-FAT; OBESE; CHILDREN; PREDICTORS; HUMANS AB Objective: To examine associations of perinatal and 3-year leptin with weight gain and adiposity through 7 years. Design and Methods: In Project Viva, plasma leptin from mothers at 26-28 weeks' gestation (n = 893), umbilical cord vein at delivery (n = 540), and children at 3 years (n = 510) was assessed in relation to BMI z-score, waist circumference, skinfold thicknesses, and dual X-ray absorptiometry body fat. Results: 50.1% of children were male and 29.5% non-white. Mean (SD) maternal, cord, and age 3 leptin concentrations were 22.9 (14.2), 8.8 (6.4), and 1.8 (1.7) ng/ml, respectively, and 3- and 7-year BMI z-scores were 0.46 (1.00) and 0.35 (0.97), respectively. After adjusting for parental and child characteristics, higher maternal and cord leptin were associated with less 3- year adiposity. For example, mean 3- year BMI z-score was 0.5 lower (95% CI: -0.7, -0.2; P-trend = 0.003) among children whose mothers' leptin concentrations were in the top versus bottom quintile. In contrast, higher age 3 leptin was associated with greater weight gain and adiposity through age 7 [e.g., change in BMI z-score from 3 to 7 years was 0.2 units (95% CI: -0.0, 0.4; P-trend =0.05)]. Conclusion: Higher perinatal leptin was associated with lower 3- year adiposity, whereas higher age 3 leptin was associated with greater weight gain and adiposity by 7 years. C1 [Boeke, Caroline E.; Villamor, Eduardo] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Boeke, Caroline E.; Villamor, Eduardo; Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Boeke, Caroline E.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston VA Healthcare Syst, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Rifas-Shiman, Sheryl L.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Rifas-Shiman, Sheryl L.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Villamor, Eduardo] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Zera, Chloe A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA 02115 USA. RP Boeke, CE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM caroline.boeke@mail.harvard.edu FU National Institutes of Health [K24 HL 068041, R01 HD 034568, T32 CA 09001] FX We thank the participants and research staff of Project Viva. This research was funded by grants from the National Institutes of Health (K24 HL 068041, R01 HD 034568, and T32 CA 09001). MWG conceptualized and designed the study, CEB and SLR carried out the analyses, and CEB, CSM, MDH, SLR, EV, CAZ, and MWG interpreted the data, critically reviewed the manuscript, and approved the final manuscript. NR 38 TC 21 Z9 21 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2013 VL 21 IS 7 BP 1430 EP 1437 DI 10.1002/oby.20314 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 204FV UT WOS:000323351400017 PM 23408391 ER PT J AU Britton, KA Wang, N Palmisano, J Corsini, E Schlett, CL Hoffmann, U Larson, MG Vasan, RS Vita, JA Mitchell, GF Benjamin, EJ Hamburg, NM Fox, CS AF Britton, Kathryn A. Wang, Na Palmisano, Joseph Corsini, Erin Schlett, Christopher L. Hoffmann, Udo Larson, Martin G. Vasan, Ramachandran S. Vita, Joseph A. Mitchell, Gary F. Benjamin, Emelia J. Hamburg, Naomi M. Fox, Caroline S. TI Thoracic Periaortic and Visceral Adipose Tissue and Their Cross-sectional Associations with Measures of Vascular Function SO OBESITY LA English DT Article ID CORONARY-HEART-DISEASE; BODY-FAT DISTRIBUTION; ENDOTHELIAL DYSFUNCTION; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; AORTIC STIFFNESS; PERIVASCULAR FAT; BRACHIAL-ARTERY; RISK-FACTORS; OBESITY AB Objective: Perivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) were associated with vascular function. Design and Methods: TAT and VAT were quantified in Framingham Heart Study participants using multidetector-computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone, and arterial tonometry (n = 2,735; 48% women; mean age, 50 years; mean body mass index [BMI], 27.7 kg/m(2)). Using multiple linear regression, the relationships between TAT, VAT, and vascular measures was examined while adjusting for cardiovascular risk factors. Results: Mean TAT and VAT volumes were 13.2 and 1763 cm(3). TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (P < 0.02); TAT was negatively associated with hyperemic mean flow velocity (P = 0.03). Associations of TAT with vascular function were attenuated after VAT adjustment (all P > 0.06). Conclusions: Thoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function. C1 [Britton, Kathryn A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Britton, Kathryn A.; Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Britton, Kathryn A.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham, MA USA. [Britton, Kathryn A.; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Wang, Na; Palmisano, Joseph] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Corsini, Erin; Schlett, Christopher L.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Evans Dept Med, Boston, MA 02118 USA. [Vita, Joseph A.; Benjamin, Emelia J.; Hamburg, Naomi M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med, Boston, MA 02118 USA. [Vita, Joseph A.; Benjamin, Emelia J.; Hamburg, Naomi M.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Cardiovasc Engn Inc, Norwood, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. Brigham & Womens Hosp, Div Endocrinol Metab & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM foxca@nhlbi.nih.gov OI Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; [RO1 HL70100]; [1ROI HL60040]; [HL077447]; [K12 HL083786] FX This study was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract N01-HC-25195), and by RO1 HL70100; 1ROI HL60040); HL077447; K12 HL083786. NR 36 TC 14 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2013 VL 21 IS 7 BP 1496 EP 1503 DI 10.1002/oby.20166 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 204FV UT WOS:000323351400026 PM 23754461 ER PT J AU Mitin, T Blute, M Lee, R Efstathiou, J AF Mitin, Timur Blute, Michael Lee, Richard Efstathiou, Jason TI Management of Lymph Node-Positive Prostate Cancer: The Role of Surgery and Radiation Therapy SO ONCOLOGY-NEW YORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; TERM-FOLLOW-UP; DELAYED ENDOCRINE TREATMENT; RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; PRIMARY TUMOR; POSTOPERATIVE RADIOTHERAPY; DEFINITIVE RADIOTHERAPY; PELVIC LYMPHADENECTOMY; ANDROGEN DEPRIVATION AB There is no clear consensus on how to manage a subset of patients with prostate cancer (PCa) who present with involved lymph nodes (LN+). Although outcomes for these patients are uniformly worse than those for patients with localized PCa, they are better than outcomes for patients with bone metastases, with more than 60% of patients alive at 10 years after the initial diagnosis. This article reviews the existing data on outcomes for patients treated with various combinations of systemic and local therapies. Current evidence suggests both a disease-control benefit and a survival benefit to multi-modality therapy, which combines systemic androgen deprivation therapy (ADT) with local therapies, such as surgery and radiation, without evidence of excessive treatment-related toxicities. C1 [Mitin, Timur; Efstathiou, Jason] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Blute, Michael] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Lee, Richard] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Mitin, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM tmitin@partners.org NR 46 TC 5 Z9 5 U1 0 U2 4 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 JUL PY 2013 VL 27 IS 7 BP 647 EP 655 PG 9 WC Oncology SC Oncology GA 196DH UT WOS:000322753100008 PM 23977759 ER PT J AU Solus, JF Kraft, S AF Solus, Jason F. Kraft, Stefan TI Ras, Raf, and MAP Kinase in Melanoma SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE melanoma; mitogen-activated protein kinase (MAPK); Raf; Ras; molecular pathology ID BRAF V600E MUTATION; FREQUENT SOMATIC MUTATIONS; HUMAN CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; METASTATIC MELANOMA; N-RAS; TUMOR PROGRESSION; NRAS MUTATIONS; UVEAL MELANOMA; HUMAN CANCER AB A growing understanding of the biology and molecular mechanisms of melanoma has led to the identification of a number of driver mutations for this aggressive tumor. The most common mutations affect signaling of the Ras/Raf/MAPK (mitogen-activated protein kinase) pathway. This review will focus on mutations in genes encoding proteins that play a role in the MAPK pathway and that have been implicated in melanoma biology, such as BRAF, NRAS, and MEK (MAPK kinase), and detail the current understanding of their role in melanoma progression from a molecular biology perspective. Furthermore, this review will also consider some additional mutations in genes such as KIT, GNAQ, and GNA11, which can be seen in certain subtypes of melanoma and whose gene products interact with the MAPK pathway. In addition, the association of these molecular changes with clinical and classical histopathologic characteristics of melanoma will be outlined and their role in diagnosis of melanocytic lesions discussed. Finally, a basic overview of the current targeted therapy landscape, as far as relevant to the pathologist, will be provided. C1 Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Solus, Jason F.; Kraft, Stefan] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kraft, S (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 831, Boston, MA 02114 USA. EM skraft@partners.org NR 146 TC 26 Z9 26 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD JUL PY 2013 VL 20 IS 4 BP 217 EP 226 DI 10.1097/PAP.0b013e3182976c94 PG 10 WC Pathology SC Pathology GA 202LU UT WOS:000323218800002 PM 23752084 ER PT J AU Caballero, AE Davidson, J Elmi, A Gavin, J Lee, K Nunlee-Bland, GL Zangeneh, F Puckrein, GA AF Caballero, A. Enrique Davidson, Jaime Elmi, Angelo Gavin, James Lee, Kenyatta Nunlee-Bland, Gail L. Zangeneh, Farhad Puckrein, Gary A. TI Previously Unrecognized Trends in Diabetes Consumption Clusters in Medicare SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID EXPENDITURES AB Objective: To examine the annual cost profiles of Medicare beneficiaries with diabetes to identify patterns in their consumption of benefits. Methods: Retrospective expenditure data were collected from Medicare records. Beneficiaries with diabetes were grouped into 5 consumption clusters ranging from "crisis consumers" at the high end to "low consumers" at the low end. Results: The percentages of beneficiaries and expenditures for the consumption clusters remained generally constant from year to year. As expected, most of Medicare's budget each year was spent on crisis, heavy, and moderate consumers. However, a notable proportion of low and light consumers from one year go on to become crisis and heavy consumers in subsequent years. A review of total 2001 through 2006 inpatient costs for the year 2000 clusters revealed that 47% of these costs were for year 2000 low and light consumers and only 27% were for year 2000 crisis and heavy consumers. Conclusions: This analysis revealed previously unrecognized trends, whereby a notable proportion of low and light consumers during one year went on to become crisis and heavy consumers in subsequent years, representing a large proportion of inpatient costs. These findings have important implications for disease management programs, which typically focus intervention efforts exclusively on crisis and heavy consumers. C1 [Caballero, A. Enrique] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Davidson, Jaime] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Elmi, Angelo] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Gavin, James] Healing Our Village, Lanham, MD USA. [Lee, Kenyatta] Commonwealth Family Practice Grp, Jacksonville, FL USA. [Nunlee-Bland, Gail L.] Howard Univ, Washington, DC 20059 USA. [Zangeneh, Farhad] George Washington Univ, Sch Med, Washington, DC USA. [Puckrein, Gary A.] Natl Minor Qual Forum, Washington, DC 20036 USA. RP Puckrein, GA (reprint author), Natl Minor Qual Forum, 1200 New Hampshire Ave NW,Ste 575, Washington, DC 20036 USA. EM gpuckrein@nmqf.org FU NIDDK NIH HHS [P30 DK079637] NR 9 TC 0 Z9 0 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2013 VL 19 IS 7 BP 541 EP 548 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 195CY UT WOS:000322681100003 PM 23919418 ER PT J AU Kruse, GR Chang, YC Kelley, JHK Linder, JA Einbinder, JS Rigotti, NA AF Kruse, Gina R. Chang, Yuchiao Kelley, Jennifer H. K. Linder, Jeffrey A. Einbinder, Jonathan S. Rigotti, Nancy A. TI Healthcare System Effects of Pay-for-Performance for Smoking Status Documentation SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; CHRONIC DISEASE MANAGEMENT; VITAL SIGN; FINANCIAL INCENTIVES; CESSATION; QUALITY; IMPACT; INTERVENTION; GUIDELINES; REGISTRY AB Objectives: To evaluate the impact on smoking status documentation of a payer-sponsored pay-for-performance (P4P) incentive that targeted a minority of an integrated healthcare delivery system's patients. Study Design: Three commercial insurers simultaneously adopted P4P incentives to document smoking status of their members with 3 chronic diseases. The healthcare system responded by adding a smoking status reminder to all patients' electronic health records (EHRs). We measured change in smoking status documentation before (2008-2009) and after (2010-2011) P4P implementation by patient P4P eligibility. Methods: The P4P-eligible patients were compared primarily with a subset of non P4P-eligible patients who resembled P4P-eligible patients and also with all non-P4P-eligible patients. Multivariate models adjusted for patient and provider characteristics and accounted for provider-level clustering and preimplementation trends. Results: Documentation increased from 48% of 207,471 patients before P4P to 71% of 227,574 patients after P4P. Improvement from 56% to 83% occurred among P4P-eligible patients (adjusted odds ratio [AOR], 3.6; 95% confidence interval [CI], 2.9-4.5) and from 56% to 80% among the comparable subset of non P4P-eligible patients (AOR, 3.0; 95% CI, 2.3-3.9). The difference in improvement between groups was significant (AOR, 1.3; 95% CI, 1.1-1.4; P = .009). Conclusions: A P4P incentive targeting a minority of a healthcare system's patients stimulated adoption of a systemwide EHR reminder and improved smoking status documentation overall. Combining a P4P incentive with an EHR reminder might help healthcare systems improve treatment delivery for smokers and meet "meaningful use" standards for EHRs. C1 [Kruse, Gina R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Dept Epidemiol, Boston, MA 02114 USA. [Kelley, Jennifer H. K.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Kruse, Gina R.; Chang, Yuchiao; Linder, Jeffrey A.; Einbinder, Jonathan S.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Kelley, Jennifer H. K.] Partners HealthCare, High Performance Med, Boston, MA USA. [Einbinder, Jonathan S.] Partners HealthCare, Clin Informat Res & Dev, Boston, MA USA. [Linder, Jeffrey A.; Einbinder, Jonathan S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Rigotti, Nancy A.] Mongan Inst Hlth Policy, Boston, MA USA. RP Kruse, GR (reprint author), 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM gkruse@partners.org FU Health Resources and Services Administration for the Harvard General Medicine Fellowship [T32HP12706-03-00]; [K24-HL08880] FX Dr Kruse was supported by grant T32HP12706-03-00 from the Health Resources and Services Administration for the Harvard General Medicine Fellowship. Dr Rigotti was supported by grant K24-HL08880. The funders of these grants had no role in study design, conduct, data analysis, interpretation, or manuscript preparation, review, or approval. NR 28 TC 5 Z9 5 U1 1 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2013 VL 19 IS 7 BP 554 EP 561 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 195CY UT WOS:000322681100004 PM 23919419 ER PT J AU Rosland, AM Nelson, K Sun, HL Dolan, ED Maynard, C Bryson, C Stark, R Shear, JM Kerr, E Fihn, SD Schectman, G AF Rosland, Ann-Marie Nelson, Karin Sun, Haili Dolan, Emily D. Maynard, Charles Bryson, Christopher Stark, Richard Shear, Joanne M. Kerr, Eve Fihn, Stephan D. Schectman, Gordon TI The Patient-Centered Medical Home in the Veterans Health Administration SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PRIMARY-CARE; TRANSFORMATION; MODEL; COST AB Background:The Veterans Health Administration (VHA) is the largest integrated US health system to implement the patient-centered medical home. The Patient Aligned CareTeam (PACT) initiative (implemented 2010-20141 aims to achieve team-based care, improved access, and care management for more than 5 million primary care patients nationwide. Objectives: To describe PACT and evaluate interim changes in PACT-related care processes. Study Design: Data from the VHA Corporate Data Warehouse were obtained from April 2009 (pre-PACT) to September 2012. All patients assigned to a primary care provider (PCP) at all VHA facilities were included. Methods: Nonparametric tests of trend across time points. Results: VHA increased primary care staff levels from April 2010 to December 2011 (2.3 to 3.0 staff per PCP full-time equivalent). In-person PCP visit rates slightly decreased from April 2009 to April 2012 (53 to 43 per 100 patients per calendar quarter; P <.01), while in-person nurse encounter rates remained steady. Large increases were seen in phone encounters (2.7 to 28.8 per 100 patients per quarter; P <.01), enhanced personal health record use (3% to 13% of patients enrolled), and electronic messaging to providers (0.01% to 2.3% of patients per quarter). Post hospitalization follow-up improved (6.6% to 61% of VA hospital discharges), but home telemonitoring (0.8% to 1.4% of patients) and group visits (0.2 to 0.65 per 100 patients per quarter; P <.01) grew slowly. Conclusions:Thirty months into PACT, primary care staff levels and phone and electronic encounters have greatly increased; other changes have been positive but slower. C1 [Rosland, Ann-Marie; Kerr, Eve] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Rosland, Ann-Marie; Kerr, Eve] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Nelson, Karin; Sun, Haili; Dolan, Emily D.; Maynard, Charles; Bryson, Christopher] Northwest HSR&D Ctr Excellence, VA Puget Sound Healthcare Syst, Seattle, WA USA. [Nelson, Karin; Bryson, Christopher] Gen Internal Med Serv, Seattle, WA USA. [Nelson, Karin; Bryson, Christopher; Fihn, Stephan D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Maynard, Charles; Fihn, Stephan D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Stark, Richard; Schectman, Gordon] VHA Off Patient Care Serv, Washington, DC USA. [Shear, Joanne M.] VHA Off Primary Care Operat & Primary Care Serv, Washington, DC USA. RP Rosland, AM (reprint author), 2215 Fuller Rd 152, Ann Arbor, MI 48105 USA. EM arosland@umich.edu RI Maynard, Charles/N-3906-2015; Rosland, Annmarie/B-7750-2016 OI Maynard, Charles/0000-0002-1644-7814; NR 25 TC 68 Z9 70 U1 4 U2 13 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2013 VL 19 IS 7 BP E263 EP + PG 22 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 195CY UT WOS:000322681100010 PM 23919446 ER PT J AU Phan, CM Khalilzadeh, O Dinkel, J Wang, IS Bredella, MA Misra, M Miller, KK Klibanski, A Gupta, R AF Phan, C. M. Khalilzadeh, O. Dinkel, J. Wang, I. S. Bredella, M. A. Misra, M. Miller, K. K. Klibanski, A. Gupta, R. TI C-arm CT for histomorphometric evaluation of lumbar spine trabecular microarchitecture: a study on anorexia nervosa patients SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID PANEL VOLUME CT; COMPUTED-TOMOGRAPHY; ADOLESCENT GIRLS; DISTAL RADIUS; WOMEN; OSTEOPOROSIS; FRACTURES; DENSITY; RISK; RATS AB Bone histomorphometry measurements require high spatial resolution that may not be feasible using multidetector CT (MDCT). This study evaluated the trabecular microarchitecture of lumbar spine using MDCT and C-arm CT in a series of young adult patients with anorexia nervosa (AN). 11 young females with AN underwent MDCT (anisotropic resolution with a slice thickness of similar to 626 mu m) and C-arm CT (isotropic resolution of 200 pm). Standard histomorphometric parameters the of L1 vertebral body, namely the apparent trabecular bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN) and trabecular separation (TbSp), were analysed using MicroView software (GE Healthcare, Piscataway, NJ). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Trabecular parameters derived from MDCT and C-arm CT were compared, and their association with F3MD parameters was evaluated. Histomorphonnetric parameters derived from C-arm CT, namely TbTh, TbN and TbSp, were significantly different from the corresponding MDCT parameters. There were no significant correlations between C-arm CT-derived parameters and the corresponding MDCT-derived parameters. C-arm CT-derived parameters were significantly (p<0.001) correlated with anteroposterior L1 spine BMD and Z-scores: TbTh (r=0.723, r=0.744, respectively), TbN.(r=-0.720, r=-0.712, respectively) and TbSp (r=0.656, r=0.648, respectively). BV/TV, derived from C-arm CT, was significantly associated with body mass index (r=0.636) and ideal body weight (r=0.730) (p<0.05). These associations were not present in MDCT-derived parameters. This study suggests that the spatial resolution offered by C-arm CT more accurately captures the histomorphometric parameters of trabecular morphology than MDCT in patients with AN. C1 [Phan, C. M.; Khalilzadeh, O.; Dinkel, J.; Wang, I. S.; Bredella, M. A.; Gupta, R.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Misra, M.; Miller, K. K.; Klibanski, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Misra, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Gupta, R (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM rgupta1@partners.org FU National Institute of Health [DK052625, 2 UL1 RR025758.] FX This work was supported by the following grants from the National Institute of Health-DK052625 and 2 UL1 RR025758. NR 29 TC 0 Z9 0 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD JUL PY 2013 VL 86 IS 1027 AR UNSP 20120451 DI 10.1259/bjr.20120451 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196UF UT WOS:000322802200001 PM 23640801 ER PT J AU Wen, SW Ager, EI Christophi, C AF Wen, Shu Wen Ager, Eleanor I. Christophi, Christopher TI Bimodal role of Kupffer cells during colorectal cancer liver metastasis SO CANCER BIOLOGY & THERAPY LA English DT Article DE macrophage; tumor-associated macrophages; Kupffer cell; liver metastases; colorectal cancer ID TUMOR-ASSOCIATED MACROPHAGES; HUMAN PROSTATE-CANCER; NITRIC-OXIDE; HEPATIC METASTASIS; RAT-LIVER; FUNCTIONAL-HETEROGENEITY; GADOLINIUM CHLORIDE; PROGNOSTIC VALUE; T-CELLS; PROGRESSION AB Kupffer cells (KCs) are resident liver macrophages that play a crucial role in liver homeostasis and in the pathogenesis of liver disease. Evidence suggests KCs have both stimulatory and inhibitory functions during tumor development but the extent of these functions remains to be defined. Using KC depletion studies in an orthotopic murine model of colorectal cancer (CRC) liver metastases we demonstrated the bimodal role of KCs in determining tumor growth. KC depletion with gadolinium chloride before tumor induction was associated with an increased tumor burden during the exponential growth phase. In contrast, KC depletion at the late stage of tumor growth (day 18) decreased liver tumor load compared with non-depleted animals. This suggests KCs exhibit an early inhibitory and a later stimulatory effect. These two opposing functions were associated with changes in iNOS and VEGF expression as well as T-cell infiltration. KC depletion at day 18 increased numbers of CD3(+) T cells and iNOS-expressing infiltrating cells in the tumor, but decreased the number of VEGF-expressing infiltrating cells. These alterations may be responsible for the observed reduction in tumor burden following depletion of pro-tumor KCs at the late stage of metastatic growth. Taken together, our results indicate that the bimodal role of KC activity in liver tumors may provide the key to timing immunomodulatory intervention for the treatment of CRC liver metastases. C1 [Wen, Shu Wen; Ager, Eleanor I.; Christophi, Christopher] Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic, Australia. [Wen, Shu Wen] Queensland Inst Med Res, Tumor Microenvironm Lab, Herston, Qld 4006, Australia. [Ager, Eleanor I.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Ager, Eleanor I.] Harvard Univ, Sch Med, Boston, MA USA. RP Wen, SW (reprint author), Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic, Australia. EM ShuWen.Wen@qimr.edu.au OI Ager, Eleanor/0000-0002-7849-9206 FU Cancer Australia's Priority-driven Collaborative Cancer Research Scheme; Cancer Australia; Cure Cancer Australia Foundation; Cancer Council of Victoria; NHMRC Post-doctoral Training Award; Australian Rotary Health Research Fund PhD Scholarship FX This work was supported by Cancer Australia's Priority-driven Collaborative Cancer Research Scheme (co-funded by Cancer Australia and Cure Cancer Australia Foundation) and by the Cancer Council of Victoria. Dr Ager was supported by an NHMRC Post-doctoral Training Award. SWW was supported by an Australian Rotary Health Research Fund PhD Scholarship. NR 41 TC 12 Z9 13 U1 1 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL 1 PY 2013 VL 14 IS 7 BP 606 EP 613 DI 10.4161/cbt.24593 PG 8 WC Oncology SC Oncology GA 200BT UT WOS:000323042400006 PM 23792646 ER PT J AU Arnason, T Pino, MS Yilmaz, O Kirley, SD Rueda, BR Chung, DC Zukerberg, LR AF Arnason, Thomas Pino, Maria S. Yilmaz, Omer Kirley, Sandra D. Rueda, Bo R. Chung, Daniel C. Zukerberg, Lawrence R. TI Cables1 is a tumor suppressor gene that regulates intestinal tumor progression in Apc(Min) mice SO CANCER BIOLOGY & THERAPY LA English DT Article DE Apc(Min)mice; Cables1; adenocarcinoma; chromosome 18q; colorectal cancer; tumor suppressor gene; -catenin ID HUMAN COLORECTAL CANCERS; IN-VIVO; MALIGNANT PROGRESSION; SOMATIC ALTERATIONS; ENDOMETRIAL CANCER; KNOCKOUT MICE; BETA-CATENIN; KINASE; CELLS; SMAD4 AB The transformation of colonic mucosal epithelium to adenocarcinoma requires progressive oncogene activation and tumor suppressor gene inactivation. Loss of chromosome 18q is common in colon cancer but not in precancerous adenomas. A few candidate tumor suppressor genes have been identified in this region, including CABLES1 at 18q11.2-12.1. This study investigates the role of CABLES1 in an in vivo mouse model of intestinal adenocarcinoma and in human colon cancer cell culture. Apc(Min/+) mice were crossed with mice harboring targeted inactivation of the Cables1 gene (Cables1(-/-)). The intestinal tumor burden and tumor expression of -catenin and PCNA was compared in Cables1(+/+)Apc(Min/+) and Cables1(-/-)Apc(Min/+) mice. -catenin activity in human colon cancer cells with CABLES1 inactivation and intestinal progenitor cell function in Cables1(-/-) mice were assayed in vitro. The mean number of small intestinal tumors per mouse was 3.1 +/- 0.6 in Cables1(+/+) Apc(Min/+) mice, compared with 32.4 +/- 3.5 in the Cables1(-/-)Apc(Min/+) mice (P < 0.0001). Fewer colonic tumors were observed in Cables1(+/+)Apc(Min/+) mice (mean 0.6 +/- 0.1) compared with the Cables1(-/-)Apc(Min/+) mice (mean 1.3 +/- 0.3, P = 0.01). Tumors from Cables1(-/-)Apc(Min/+) mice demonstrated increased nuclear expression of -catenin and an increased number of PCNA-positive cells. In vitro studies revealed that CABLES1 deficiency increased -catenin dependent transcription and increased intestinal progenitor cell activity. Loss of Cables1 enhances tumor progression in the Apc(Min/+) mouse model and activates the Wnt/-catenin signaling pathway. Cables1 is a tumor suppressor gene on chromosome 18q in this in vivo mouse model and likely has a similar role in human colon cancer. C1 [Arnason, Thomas; Yilmaz, Omer; Kirley, Sandra D.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arnason, Thomas; Pino, Maria S.; Yilmaz, Omer; Kirley, Sandra D.; Rueda, Bo R.; Chung, Daniel C.; Zukerberg, Lawrence R.] Harvard Univ, Boston, MA 02115 USA. [Pino, Maria S.; Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Pino, Maria S.] Azienda Sanit Firenze, Dept Oncol, Med Oncol Unit, Florence, Italy. [Rueda, Bo R.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Chung, Daniel C.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Zukerberg, LR (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM lzukerberg@partners.org FU National Institute of Health [R01 CA103883]; Royal College of Physicians and surgeons of Canada; Dalhousie University FX The study was funded through National Institute of Health Grant R01 CA103883 entitled "Cables and the colonocyte". TA was funded through scholarships from the Royal College of Physicians and surgeons of Canada (Detweiler Traveling fellowship) and Dalhousie University (McLoughlin Scholarship). NR 29 TC 7 Z9 7 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL 1 PY 2013 VL 14 IS 7 BP 672 EP 678 DI 10.4161/cbt.25089 PG 7 WC Oncology SC Oncology GA 200BT UT WOS:000323042400012 PM 23792637 ER PT J AU Lyssiotis, CA Son, J Cantley, LC Kimmelman, AC AF Lyssiotis, Costas A. Son, Jaekyoung Cantley, Lewis C. Kimmelman, Alec C. TI Pancreatic cancers rely on a novel glutamine metabolism pathway to maintain redox balance SO CELL CYCLE LA English DT Article DE cancer metabolism; NADPH; aspartate aminotransferase; malic enzyme; glutamate dehydrogenase ID CELL-PROLIFERATION C1 [Lyssiotis, Costas A.; Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Son, Jaekyoung; Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Weill Cornell Med Coll, Dept Med, New York, NY USA. EM Lcantley@med.cornell.edu; Alec_Kimmelman@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [R01 CA157490, P01 CA117969]; NIGMS NIH HHS [R01 GM056203] NR 7 TC 17 Z9 17 U1 1 U2 15 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2013 VL 12 IS 13 BP 1987 EP 1988 DI 10.4161/cc.25307 PG 2 WC Cell Biology SC Cell Biology GA 201VI UT WOS:000323170700005 PM 23759579 ER PT J AU Xiong, Y Sheen, J AF Xiong, Yan Sheen, Jen TI Moving beyond translation Glucose-TOR signaling in the transcriptional control of cell cycle SO CELL CYCLE LA English DT Article DE target of rapamycin; E2Fa; Arabidopsis thaliana; meristem; transcriptional control; cell cycle ID GROWTH; MTOR C1 [Xiong, Yan; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Xiong, Yan; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xiong, Yan; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Xiong, Yan] Chinese Acad Sci, Shanghai Ctr Plant Stress Biol, Shanghai, Peoples R China. RP Xiong, Y (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM xiong@molbio.mgh.harvard.edu NR 8 TC 12 Z9 12 U1 0 U2 19 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2013 VL 12 IS 13 BP 1989 EP 1990 DI 10.4161/cc.25308 PG 2 WC Cell Biology SC Cell Biology GA 201VI UT WOS:000323170700006 PM 23759578 ER PT J AU Yin, Q Sester, DP Tian, Y Hsiao, YS Lu, A Cridland, JA Sagulenko, V Thygesen, SJ Choubey, D Hornung, V Walz, T Stacey, KJ Wu, H AF Yin, Qian Sester, David P. Tian, Yuan Hsiao, Yu-Shan Lu, Alvin Cridland, Jasmyn A. Sagulenko, Vitaliya Thygesen, Sara J. Choubey, Divaker Hornung, Veit Walz, Thomas Stacey, Katryn J. Wu, Hao TI Molecular Mechanism for p202-Mediated Specific Inhibition of AIM2 Inflammasome Activation SO CELL REPORTS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON-INDUCIBLE PROTEIN; DNA-BINDING DOMAIN; CYCLIC GMP-AMP; CELL-DEATH; ENDOGENOUS RETROVIRUSES; ELECTRON-MICROSCOPY; MURINE MACROPHAGES; INTRACELLULAR DNA; CYTOPLASMIC DNA AB Mouse p202 containing two hemopoietic expression, interferon inducibility, nuclear localization (HIN) domains antagonizes AIM2 inflammasome signaling and potentially modifies lupus susceptibility. We found that only HIN1 of p202 binds double-stranded DNA (dsDNA), while HIN2 forms a homotetramer. Crystal structures of HIN1 revealed that dsDNA is bound on face opposite the site used in AIM2 and IFI16. The structure of HIN2 revealed a dimer of dimers, the face analogous to the HIN1 dsDNA binding site being a dimerization interface. Electron microscopy imaging showed that HIN1 is flexibly linked to HIN2 in p202, and tetramerization provided enhanced avidity for dsDNA. Surprisingly, HIN2 of p202 interacts with the AIM HIN domain. We propose that this results in a spatial separation of the AIM2 pyrin domains, and indeed p202 prevented the dsDNA-dependent clustering of apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) and AIM2 inflammasome activation. We hypothesize that while p202 was evolutionarily selected to limit AIM2-mediated inflammation in some mouse strains, the same mechanism contributes to increased interferon production and lupus susceptibility. C1 [Yin, Qian; Lu, Alvin; Wu, Hao] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yin, Qian; Lu, Alvin; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Sester, David P.; Cridland, Jasmyn A.; Sagulenko, Vitaliya; Thygesen, Sara J.; Stacey, Katryn J.] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia. [Tian, Yuan] Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA. [Hsiao, Yu-Shan; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Choubey, Divaker] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Hornung, Veit] Univ Bonn, Univ Hosp, Unit Clin Biochem, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany. RP Stacey, KJ (reprint author), Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia. EM katryn.stacey@uq.edu.au; hao.wu@childrens.harvard.edu RI Hornung, Veit/C-3565-2012 OI Lu, Alvin/0000-0003-2353-848X; Hornung, Veit/0000-0002-4150-194X FU NIAID NIH HHS [R01 AI050872] NR 56 TC 31 Z9 32 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JUL PY 2013 VL 4 IS 2 BP 327 EP 339 DI 10.1016/j.celrep.2013.06.024 PG 13 WC Cell Biology SC Cell Biology GA 195LR UT WOS:000322704400010 PM 23850291 ER PT J AU O'Rourke, JG Gareau, JR Ochaba, J Song, W Rasko, T Reverter, D Lee, J Monteys, AM Pallos, J Mee, L Vashishtha, M Apostol, BL Nicholson, TP Illes, K Zhu, YZ Dasso, M Bates, GP Difiglia, M Davidson, B Wanker, EE Marsh, JL Lima, CD Steffan, JS Thompson, LM AF O'Rourke, Jacqueline Gire Gareau, Jaclyn R. Ochaba, Joseph Song, Wan Rasko, Tamas Reverter, David Lee, John Monteys, Alex Mas Pallos, Judit Mee, Lisa Vashishtha, Malini Apostol, Barbara L. Nicholson, Thomas Peter Illes, Katalin Zhu, Ya-Zhen Dasso, Mary Bates, Gillian P. Difiglia, Marian Davidson, Beverly Wanker, Erich E. Marsh, J. Lawrence Lima, Christopher D. Steffan, Joan S. Thompson, Leslie M. TI SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation SO CELL REPORTS LA English DT Article ID DISEASE PATHOGENESIS; POSTTRANSLATIONAL MODIFICATIONS; INTERACTION NETWORK; CONJUGATION; AGGREGATION; SUMOYLATION; REPEAT; MICE; GENE; ACTIVATION AB A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression. C1 [O'Rourke, Jacqueline Gire; Thompson, Leslie M.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. [O'Rourke, Jacqueline Gire; Mee, Lisa; Vashishtha, Malini; Apostol, Barbara L.; Illes, Katalin; Zhu, Ya-Zhen; Steffan, Joan S.; Thompson, Leslie M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. [O'Rourke, Jacqueline Gire; Ochaba, Joseph; Vashishtha, Malini; Steffan, Joan S.; Thompson, Leslie M.] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA 92697 USA. [Gareau, Jaclyn R.; Reverter, David; Lima, Christopher D.] Sloan Kettering Inst, Struct Biol Program, New York, NY 10065 USA. [Ochaba, Joseph; Thompson, Leslie M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Song, Wan; Pallos, Judit; Marsh, J. Lawrence] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. [Rasko, Tamas; Wanker, Erich E.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. [Lee, John; Monteys, Alex Mas; Davidson, Beverly] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. [Lee, John; Monteys, Alex Mas; Davidson, Beverly] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA. [Lee, John; Monteys, Alex Mas; Davidson, Beverly] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA. [Nicholson, Thomas Peter] Enzo Life Sci UK Ltd, Exeter EX2 8NL, Devon, England. [Dasso, Mary] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Bates, Gillian P.] Kings Coll London, Sch Med, Dept Med & Mol Genet, London WC2R 2LS, England. [Difiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Difiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Thompson, LM (reprint author), Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. EM lmthomps@uci.edu OI Reverter, David/0000-0002-5347-0992; Bates, Gillian/0000-0002-4041-6305; Dasso, Mary/0000-0002-5410-1371; Wanker, Erich/0000-0001-8072-1630; Lima, Christopher/0000-0002-9163-6092 FU National Institutes of Health [NS-52789, NS-45283, U01-NS063953, NS072453, GM065872]; DFG; EU [SFB740, SFB618]; EU (EuroSpin); EU (SynSys); Janet Westerfield Foundation; Hereditary Disease Foundation; CHDI Foundation; Huntington's Disease Society of America; Optical Biology Shared Resource of the Cancer Center Support Grant at the University of California, Irvine [CA-62203] FX This work was supported by grants from the National Institutes of Health: NS-52789 to L. M. T., NS-45283 to J.L.M., U01-NS063953 subaward to L. M. T. and J.L.M., and NS072453 to J.S.S. C. D. L., D. R., and J.R.G. were supported in part by GM065872, the DFG, and EU (SFB740, SFB618, EuroSpin, and SynSys to E. E. W.), and J.O. received support from the Janet Westerfield Foundation. Support was also provided by the Hereditary Disease Foundation (to L. M. T. and J.S.S.), CHDI Foundation (to J.L.M., L. M. T., and J.S.S.), and Huntington's Disease Society of America (to L. M. T. and J.L.M.). We would like to thank Ron Hay for His-SUMO-1/2/3 plasmids and many helpful discussions, Hongtao Yu for the GFP-SUMO-1/2 plasmids, Solomon H. Snyder for the Rhes plasmid, and T. P. Yao for HDAC4 plasmids. We also thank Emily Mitchell for assistance with filter retardation assays and Jack Reidling for careful reading of the manuscript. We also acknowledge the Massachusetts Alzheimer's Disease Research Center for human autopsy brain tissue. We acknowledge assistance from Hediye Erdjument-Bromage and the Mass Spectrometry facility at Sloan-Kettering Institute for performing and analyzing mass spectra data (Figure S1). This work was made possible in part by the availability of the Optical Biology Shared Resource of the Cancer Center Support Grant (CA-62203) at the University of California, Irvine. NR 66 TC 19 Z9 20 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JUL PY 2013 VL 4 IS 2 BP 362 EP 375 DI 10.1016/j.celrep.2013.06.034 PG 14 WC Cell Biology SC Cell Biology GA 195LR UT WOS:000322704400013 PM 23871671 ER PT J AU Dominy, JE Puigserver, P AF Dominy, John E. Puigserver, Pere TI Mitochondrial Biogenesis through Activation of Nuclear Signaling Proteins SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID FATTY-ACID OXIDATION; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; RECEPTOR-GAMMA COACTIVATOR-1-ALPHA; YIN YANG 1; SKELETAL-MUSCLE; GENE-EXPRESSION; CALORIE RESTRICTION; CYTOCHROME-C; ERR-ALPHA; ENERGY-EXPENDITURE AB The dynamics of mitochondrial biogenesis and function is a complex interplay of cellular and molecular processes that ultimately shape bioenergetics capacity. Mitochondrial mass, by itself, represents the net balance between rates of biogenesis and degradation. Mitochondrial biogenesis is dependent on different signaling cascades and transcriptional complexes that promote the formation and assembly of mitochondria-a process that is heavily dependent on timely and coordinated transcriptional control of genes encoding for mitochondrial proteins. In this article, we discuss the major signals and transcriptional complexes, programming mitochondrial biogenesis, and bioenergetic activity. This regulatory network represents a new therapeutic window into the treatment of the wide spectrum of mitochondrial and neurodegenerative diseases characterized by dysregulation of mitochondrial dynamics and bioenergetic deficiencies. C1 [Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM pere_puigserver@dfci.harvard.edu FU Dana-Farber Cancer Institute funds; NIH/NIDDK; American Diabetes Association; American Heart Association; Muscle Dystrophy Association FX Mitochondrial-related research in the Puigserver laboratory is supported from the Dana-Farber Cancer Institute funds and grants from the NIH/NIDDK, American Diabetes Association, American Heart Association, and Muscle Dystrophy Association. NR 121 TC 10 Z9 11 U1 0 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JUL PY 2013 VL 5 IS 7 AR a015008 DI 10.1101/cshperspect.a015008 PG 16 WC Cell Biology SC Cell Biology GA 200EW UT WOS:000323051600008 ER PT J AU Braunstein, I Werth, V AF Braunstein, Inbal Werth, Victoria TI Treatment of dermatologic connective tissue disease and autoimmune blistering disorders in pregnancy SO DERMATOLOGIC THERAPY LA English DT Article DE autoimmune skin disease; blistering disease; blistering disorders; cutaneous lupus erythematosus; dermatomyositis; lactation; morphea; pemphigoid gestationis; pemphigus foliaceus; pemphigus vulgaris; pregnancy; rheumatic skin disease ID OF-THE-LITERATURE; INFLAMMATORY-BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; PEMPHIGOID GESTATIONIS; MYCOPHENOLATE-MOFETIL; REPRODUCTIVE-SYSTEM; ANTIRHEUMATIC DRUGS; CORTICOSTEROID USE; LUPUS PREGNANCY; OCULAR TOXICITY AB Autoimmune skin disease occurs in pregnancy, and treatment is often required to control both maternal disease and fetal outcomes. Here we present the available safety data in pregnancy and lactation for medications used to treat autoimmune skin diseases, including cutaneous lupus erythematosus, dermatomyositis, morphea and systemic sclerosis, pemphigus vulgaris, pemphigus foliaceus, and pemphigoid gestationis. A PubMed search of the English-language literature using keywords, "pregnancy" "rheumatic disease," and "connective tissue disease" was performed. Relevant articles found in the search and references were included. Reasonable evidence supports the careful and cautious use of topical steroids, topical calcineurin inhibitors, systemic corticosteroids, hydroxychloroquine, and azathioprine in pregnancy. Case reports or clinical experience suggest intravenous immunoglobulin, dapsone, phototherapy, rituximab, and plasmapheresis may be safe. Several treatment options exist for autoimmune skin disease in pregnancy and lactation, and should be considered when treating these patients. C1 [Braunstein, Inbal; Werth, Victoria] Univ Penn, Philadelphia Vet Affairs Med Ctr, Div Dermatol, Philadelphia, PA 19104 USA. [Braunstein, Inbal; Werth, Victoria] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Werth, V (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM, Suite 1-330S,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Merit Review Grant from the CDC; Department of Veterans Affairs Veterans Health Administration; Office of Research and Development; Biomedical Laboratory Research and Development; National Institutes of Health [NIH K24-AR 02207] FX Grant support: Merit Review Grant from the CDC, Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and by the National Institutes of Health (NIH K24-AR 02207) to Dr. Victoria P. Werth. NR 62 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 EI 1529-8019 J9 DERMATOL THER JI Dermatol. Ther. PD JUL PY 2013 VL 26 IS 4 SI SI BP 354 EP 363 DI 10.1111/dth.12076 PG 10 WC Dermatology SC Dermatology GA 195RA UT WOS:000322720100011 PM 23914893 ER PT J AU de Melo, WCMA Avci, P de Oliveira, MN Gupta, A Vecchio, D Sadasivam, M Chandran, R Huang, YY Yin, R Perussi, LR Tegos, GP Perussi, JR Dai, TH Hamblin, MR AF de Melo, Wanessa C. M. A. Avci, Pinar de Oliveira, Milene Nobrega Gupta, Asheesh Vecchio, Daniela Sadasivam, Magesh Chandran, Rakkiyappan Huang, Ying-Ying Yin, Rui Perussi, Livia R. Tegos, George P. Perussi, Janice R. Dai, Tianhong Hamblin, Michael R. TI Photodynamic inactivation of biofilm: taking a lightly colored approach to stubborn infection SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE antimicrobial photodynamic therapy; biofilm; dental infection; extracellular polysaccharide; microbial resistance; multidrug efflux pump; persister cells; photosensitizers ID PSEUDOMONAS-AERUGINOSA BIOFILMS; CANDIDA-ALBICANS BIOFILMS; MULTIDRUG EFFLUX PUMPS; SELECTIVE ANTIMICROBIAL PHOTOSENSITIZERS; GOLD NANOPARTICLES ENHANCE; DENTAL PLAQUE BACTERIA; TOLUIDINE-BLUE-O; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; IN-VITRO AB Microbial biofilms are responsible for a variety of microbial infections in different parts of the body, such as urinary tract infections, catheter infections, middle-ear infections, gingivitis, caries, periodontitis, orthopedic implants, and so on. The microbial biofilm cells have properties and gene expression patterns distinct from planktonic cells, including phenotypic variations in enzymic activity, cell wall composition and surface structure, which increase the resistance to antibiotics and other antimicrobial treatments. There is consequently an urgent need for new approaches to attack biofilm-associated microorganisms, and antimicrobial photodynamic therapy (aPDT) may be a promising candidate. aPDT involves the combination of a nontoxic dye and low-intensity visible light which, in the presence of oxygen, produces cytotoxic reactive oxygen species. It has been demonstrated that many biofilms are susceptible to aPDT, particularly in dental disease. This review will focus on aspects of aPDT that are designed to increase efficiency against biofilms modalities to enhance penetration of photosensitizer into biofilm, and a combination of aPDT with biofilm-disrupting agents. C1 [de Melo, Wanessa C. M. A.; Avci, Pinar; Gupta, Asheesh; Vecchio, Daniela; Sadasivam, Magesh; Chandran, Rakkiyappan; Huang, Ying-Ying; Yin, Rui; Tegos, George P.; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [de Melo, Wanessa C. M. A.; Avci, Pinar; Gupta, Asheesh; Vecchio, Daniela; Huang, Ying-Ying; Yin, Rui; Tegos, George P.; Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [de Melo, Wanessa C. M. A.; de Oliveira, Milene Nobrega; Perussi, Janice R.] Univ Sao Paulo, Programa Posgrad Interunidades Bioengn ESCI FMRP, Sao Paulo, Brazil. [Gupta, Asheesh] Def Inst Physiol & Allied Sci, Delhi 110054, India. [Sadasivam, Magesh; Chandran, Rakkiyappan] Amity Univ, Amity Inst Nanotechnol, Noida, Uttar Pradesh, India. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Perussi, Livia R.] Univ Estadual Paulista UNESP, Sao Paulo, Brazil. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) FX The authors were supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). 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 225 TC 21 Z9 21 U1 5 U2 45 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JUL PY 2013 VL 11 IS 7 BP 669 EP 693 DI 10.1586/14787210.2013.811861 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 202OU UT WOS:000323228200006 PM 23879608 ER PT J AU Goyal, RK AF Goyal, Raj K. TI Seventy Years of GASTROENTEROLOGY (1943-2013) SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Goyal, Raj K.] VA Boston HealthCare Syst, Dept Internal Med, Boston, MA USA. [Goyal, Raj K.] Harvard Univ, Sch Med, Boston, MA USA. RP Goyal, RK (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU PHS HHS [062867] NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2013 VL 145 IS 1 BP 1 EP 15 DI 10.1053/j.gastro.2013.05.020 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172ZR UT WOS:000321047300007 PM 23806783 ER PT J AU Fordtran, JS Goyal, RK Feldman, M Soll, AH Trier, JS Ockner, RK Larusso, NF Podolsky, DK Brenner, DA Rustgi, AK Omary, MB Alvarez, WC Ivy, AC Aaron, AH Grossman, MI Sleisenger, MH Donaldson, RM AF Fordtran, John S. Goyal, Raj K. Feldman, Mark Soll, Andrew H. Trier, Jerry S. Ockner, Robert K. Larusso, Nicholas F. Podolsky, Daniel K. Brenner, David A. Rustgi, Anil K. Omary, M. Bishr Alvarez, Walter C. Ivy, Andrew Convay Aaron, Abraham H. Grossman, Morton I. Sleisenger, Marvin H. Donaldson, Robert M. TI Historical and Personal Perspectives of Their Editorships SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Fordtran, John S.; Alvarez, Walter C.] Baylor Univ, Med Ctr, Dept Internal Med, Dallas, TX USA. [Goyal, Raj K.; Ivy, Andrew Convay; Sleisenger, Marvin H.] VA Boston Healthcare Syst, Dept Internal Med, Boston, MA USA. [Goyal, Raj K.; Soll, Andrew H.; Ivy, Andrew Convay; Sleisenger, Marvin H.; Donaldson, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. [Feldman, Mark; Grossman, Morton I.] Texas Hlth Presbyterian Hosp Dallas, Dept Internal Med, Dallas, TX USA. [Feldman, Mark; Grossman, Morton I.] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Soll, Andrew H.; Grossman, Morton I.] Univ Calif Los Angeles, Geffen Sch Med, Dept Internal Med, Los Angeles, CA USA. [Trier, Jerry S.; Donaldson, Robert M.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Ockner, Robert K.] Univ Calif San Francisco, Med Ctr, Dept Med & Liver Ctr, San Francisco, CA 94143 USA. [Larusso, Nicholas F.] Mayo Med Sch Clin & Fdn, Ctr Basic Res Digest Dis, Div Gastroenterol & Hepatol, Rochester, MN USA. [Podolsky, Daniel K.] UT Southwestern Med Ctr, Dept Internal Med, Dallas, TX USA. [Brenner, David A.] Univ Calif, San Diego Sch Med, La Jolla, CA USA. [Rustgi, Anil K.] Univ Penn, Dept Med, Gastrointestinal Div, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Omary, M. Bishr] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. RP Goyal, RK (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu NR 1 TC 1 Z9 1 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2013 VL 145 IS 1 BP 16 EP 31 DI 10.1053/j.gastro.2013.05.019 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172ZR UT WOS:000321047300008 PM 23806784 ER PT J AU Thompson, CC Chand, B Chen, YK DeMarco, DC Miller, L Schweitzer, M Rothstein, RI Lautz, DB Slattery, J Ryan, MB Brethauer, S Schauer, P Mitchell, MC Starpoli, A Haber, GB Catalano, MF Edmundowicz, S Fagnant, AM Kaplan, LM Roslin, MS AF Thompson, Christopher C. Chand, Bipan Chen, Yang K. DeMarco, Daniel C. Miller, Larry Schweitzer, Michael Rothstein, Richard I. Lautz, David B. Slattery, James Ryan, Michele B. Brethauer, Stacy Schauer, Phillip Mitchell, Mack C. Starpoli, Anthony Haber, Gregory B. Catalano, Marc F. Edmundowicz, Steven Fagnant, Annette M. Kaplan, Lee M. Roslin, Mitchell S. TI Endoscopic Suturing for Transoral Outlet Reduction Increases Weight Loss After Roux-en-Y Gastric Bypass Surgery SO GASTROENTEROLOGY LA English DT Article DE Endocinch; Overstitch; Stomaphyx; Dilated Anastomosis ID REOPERATIVE BARIATRIC SURGERY; RESTRICTIVE PROCEDURES; LAPAROSCOPIC REVISION; REGAIN; STOMA; POUCH; EXPERIENCE; DILATION; OBESITY; GAIN AB BACKGROUND & AIMS: Weight regain or insufficient loss after Roux-en-Y gastric bypass (RYGB) is common. This is partially attributable to dilatation of the gastrojejunostomy (GJ), which diminishes the restrictive capacity of RYGB. Endoluminal interventions for GJ reduction are being explored as alternatives to revision surgery. We performed a randomized, blinded, sham-controlled trial to evaluate weight loss after sutured transoral outlet reduction (TORe). METHODS: Patients with weight regain or inadequate loss after RYGB and GJ diameter greater than 2 cm were assigned randomly to groups that underwent TORe (n = 50) or a sham procedure (controls, n = 27). Intraoperative performance, safety, weight loss, and clinical outcomes were assessed. RESULTS: Subjects who received TORe had a significantly greater mean percentage weight loss from baseline (3.5%; 95% confidence interval, 1.8%-5.3%) than controls (0.4%; 95% confidence interval, 2.3% weight gain to 3.0% weight loss) (P = .021), using a last observation carried forward intent-to-treat analysis. As-treated analysis also showed greater mean percentage weight loss in the TORe group than controls (3.9% and 0.2%, respectively; P = .014). Weight loss or stabilization was achieved in 96% subjects receiving TORe and 78% of controls (P = .019). The TORe group had reduced systolic and diastolic blood pressure (P < .001) and a trend toward improved metabolic indices. In addition, 85% of the TORe group reported compliance with the healthy lifestyle eating program, compared with 53.8% of controls; 83% of TORe subjects said they would undergo the procedure again, and 78% said they would recommend the procedure to a friend. The groups had similar frequencies of adverse events. CONCLUSIONS: A multicenter randomized trial provides Level I evidence that TORe reduces weight regain after RYGB. These results were achieved using a superficial suction-based device; greater levels of weight loss could be achieved with newer, full-thickness suturing devices. TORe is one approach to avoid weight regain; a longitudinal multidisciplinary approach with dietary counseling and behavioral changes are required for long-term results. ClinicalTrials.gov identifier: NCT00394212. C1 [Thompson, Christopher C.; Slattery, James; Ryan, Michele B.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Lautz, David B.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Chand, Bipan] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Chen, Yang K.] Univ Colorado Hosp, Div Gastroenterol, Aurora, CO USA. [DeMarco, Daniel C.] Baylor Univ, Med Ctr, Div Gastroenterol, Dallas, TX USA. [Miller, Larry] Temple Univ Hosp & Med Sch, Gastroenterol Sect, Philadelphia, PA 19140 USA. [Schweitzer, Michael] Johns Hopkins Bayview Med Ctr, Dept Bariatr Surg, Baltimore, MD USA. [Mitchell, Mack C.] Johns Hopkins Bayview Med Ctr, Div Gastroenterol, Baltimore, MD USA. [Rothstein, Richard I.] Dartmouth Hitchcock Med Ctr, Gastroenterol Sect, Lebanon, NH 03766 USA. [Brethauer, Stacy; Schauer, Phillip] Cleveland Clin Fdn, Surg Inst, Cleveland, OH 44195 USA. [Starpoli, Anthony; Haber, Gregory B.] Lenox Hill Hosp, Div Gastroenterol, New York, NY 10021 USA. [Catalano, Marc F.] St Lukes Med Ctr, Div Gastroenterol, Milwaukee, WI USA. [Edmundowicz, Steven] Washington Univ, Sch Med, Div Gastroenterol, St Louis, MO 63110 USA. [Fagnant, Annette M.] Davol Inc, Foster, RI USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Roslin, Mitchell S.] Lenox Hill Hosp, Dept Gen Surg, New York, NY 10021 USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St,Thorn 14, Boston, MA 02115 USA. EM cthompson@hms.harvard.edu OI Edmundowicz, Steven/0000-0002-6541-3485 FU Davol, Inc (Warwick, RI) of CR Bard, Inc. FX Supported by Davol, Inc (Warwick, RI), a subsidiary of CR Bard, Inc. NR 36 TC 23 Z9 23 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 JUL PY 2013 VL 145 IS 1 BP 129 EP + DI 10.1053/j.gastro.2013.04.002 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172ZR UT WOS:000321047300027 PM 23567348 ER PT J AU Martin, MG Lindberg, I Solorzano-Vargas, RS Wang, JF Avitzur, Y Bandsma, R Sokollik, C Lawrence, S Pickett, LA Chen, ZJ Egritas, O Dalgic, B Albornoz, V de Ridder, L Hulst, J Gok, F Aydogan, A Al-Hussaini, A Gok, DE Yourshaw, M Wu, SV Cortina, G Stanford, S Georgia, S AF Martin, Martin G. Lindberg, Iris Solorzano-Vargas, R. Sergio Wang, Jiafang Avitzur, Yaron Bandsma, Robert Sokollik, Christiane Lawrence, Sarah Pickett, Lindsay A. Chen, Zijun Egritas, Odul Dalgic, Buket Albornoz, Valeria de Ridder, Lissy Hulst, Jessie Gok, Faysal Aydogan, Aysen Al-Hussaini, Abdulrahman Gok, Deniz Engin Yourshaw, Michael Wu, S. Vincent Cortina, Galen Stanford, Sara Georgia, Senta TI Congenital Proprotein Convertase 1/3 Deficiency Causes Malabsorptive Diarrhea and Other Endocrinopathies in a Pediatric Cohort SO GASTROENTEROLOGY LA English DT Article DE Genetic; Congenital Diarrheal Disorder; Enteroendocrine Development; Neurogenin ID PROHORMONE CONVERTASES; OBESITY; PC1; MUTATIONS; HORMONE; GENE; MICE; HYPERPHAGIA; EXPRESSION; DEFECTS AB BACKGROUND & AIMS: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. METHODS: We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. RESULTS: We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. CONCLUSIONS: In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption. C1 [Martin, Martin G.; Solorzano-Vargas, R. Sergio; Wang, Jiafang; Chen, Zijun; Stanford, Sara] Mattel Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Los Angeles, CA 90095 USA. [Yourshaw, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Cortina, Galen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Georgia, Senta] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lindberg, Iris; Pickett, Lindsay A.; Albornoz, Valeria] Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Avitzur, Yaron; Bandsma, Robert; Sokollik, Christiane] Univ Toronto, Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada. [Lawrence, Sarah] Childrens Hosp Eastern Ontario, Div Endocrinol & Metab, Ottawa, ON K1H 8L1, Canada. [Egritas, Odul; Dalgic, Buket] Gazi Univ, Sch Med, Dept Pediat Gastroenterol, Ankara, Turkey. [de Ridder, Lissy; Hulst, Jessie] Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands. [Gok, Faysal] Gulhane Mil Med Acad, Sch Med, Dept Pediat Nephrol, Ankara, Turkey. [Gok, Deniz Engin] Gulhane Mil Med Acad, Sch Med, Dept Endocrinol, Ankara, Turkey. [Aydogan, Aysen] Kocaeli Univ, Dept Pediat Gastroenterol Hepatol & Nutr, Fac Med, Kocaeli, Turkey. [Al-Hussaini, Abdulrahman] King Fahad Med City, Childrens Hosp, Riyadh, Saudi Arabia. [Wu, S. Vincent] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Martin, MG (reprint author), Mattel Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Los Angeles, CA 90095 USA. EM mmartin@mednet.ucla.edu RI Solorano, Sergio/D-4869-2016; Egritas Gurkan, Odul/O-1363-2016; Yourshaw, Michael/F-9807-2015 OI Egritas Gurkan, Odul/0000-0003-0230-7551; Yourshaw, Michael/0000-0001-7612-0437 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK083762]; National Institute of Drug Abuse [DA05084]; California Institute of Regenerative Medicine (CIRM) [RT2-01985] FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK083762 to MGM) and the National Institute of Drug Abuse (DA05084 to IL); and the California Institute of Regenerative Medicine (CIRM), RT2-01985 to MGM. NR 28 TC 35 Z9 35 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2013 VL 145 IS 1 BP 138 EP 148 DI 10.1053/j.gastro.2013.03.048 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172ZR UT WOS:000321047300028 PM 23562752 ER PT J AU Pollastri, AR Epstein, LD Heath, GH Ablon, JS AF Pollastri, Alisha R. Epstein, Lawrence D. Heath, Georgina H. Ablon, J. Stuart TI The Collaborative Problem Solving Approach: Outcomes Across Settings SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE children; Collaborative Problem Solving; externalizing; family; inpatient; juvenile justice; oppositional defiant disorder; residential; school; Think Kids ID OPPOSITIONAL-DEFIANT DISORDER; DISRUPTIVE BEHAVIOR; SPECIAL SECTION; TEACHER STRESS; RESTRAINT; SECLUSION; CHILDREN; INPATIENT; ADOLESCENTS; PREVALENCE AB In the last decade, Collaborative Problem Solving (CPS) has become a popular approach to managing the challenging behaviors of children and adolescents, and has established a growing evidence base for reducing oppositional behavior and related outcomes. In contrast with standard behavioral methods that provide incentives for meeting adult expectations, CPS focuses on identifying and treating lagging cognitive skills that interfere with children's ability to meet these expectations. Since the majority of CPS outcomes have been evaluated in clinical and educational settings as part of internal quality-improvement efforts, only a small proportion of these findings has been published in peer-reviewed academic journals. Here, we describe the CPS approach and provide a summary of all known published and unpublished findings related to its implementation in outpatient, inpatient, residential, juvenile justice, and educational settings. Finally, we provide specific recommendations for future research on the model. C1 [Pollastri, Alisha R.; Epstein, Lawrence D.; Ablon, J. Stuart] Harvard Univ, Sch Med, Boston, MA USA. [Pollastri, Alisha R.; Epstein, Lawrence D.; Ablon, J. Stuart] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Heath, Georgina H.] St Andrews Healthcare, Northampton, England. RP Pollastri, AR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM apollastri@partners.org NR 44 TC 3 Z9 3 U1 3 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2013 VL 21 IS 4 BP 188 EP 199 DI 10.1097/HRP.0b013e3182961017 PG 12 WC Psychiatry SC Psychiatry GA 197HR UT WOS:000322841300003 PM 24651507 ER PT J AU Mehrmann, C Karmacharya, R AF Mehrmann, Craig Karmacharya, Rakesh TI Principles and Neurobiological Correlates of Concentrative, Diffuse, and Insight Meditation SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE Buddhism; central executive network; default mode network; diffuse attention; focused attention; insight; intrinsic connectivity network; meditation; mindfulness; salience network ID TELOMERE LENGTH; DEFAULT MODE; LONG-TERM; MINDFULNESS MEDITATION; COMPASSION MEDITATION; LEARNED HELPLESSNESS; COGNITIVE THERAPY; PERCEIVED CONTROL; PERSONAL MASTERY; STRESS C1 [Mehrmann, Craig; Karmacharya, Rakesh] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Karmacharya, Rakesh] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Karmacharya, Rakesh] Broad Inst Harvard, Chem Biol Program, Belmont, MA USA. [Karmacharya, Rakesh] MIT, Belmont, MA USA. [Karmacharya, Rakesh] McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02178 USA. RP Karmacharya, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM karmacharya@mcb.harvard.edu FU National Institutes of Health Mentored Clinical Scientist Research Career Development Award [K08MH086846] FX Supported, in part, by National Institutes of Health Mentored Clinical Scientist Research Career Development Award no. K08MH086846 (RK). NR 104 TC 3 Z9 3 U1 7 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2013 VL 21 IS 4 BP 205 EP 218 DI 10.1097/HRP.0b013e31828e8ef4 PG 14 WC Psychiatry SC Psychiatry GA 197HR UT WOS:000322841300005 PM 24651509 ER PT J AU Niessner, H Schmitz, J Schmid, A Calaminus, C Pichler, BJ Forschner, A Flaherty, K Honegger, JB Dummer, R Tabatabai, G Quintanilla-Fend, L Garbe, C Meier, F AF Niessner, H. Schmitz, J. Schmid, A. Calaminus, C. Pichler, B. J. Forschner, A. Flaherty, K. Honegger, J. B. Dummer, R. Tabatabai, G. Quintanilla-Fend, L. Garbe, C. Meier, F. TI The PI3K Inhibitor BKM120 has Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Niessner, H.; Forschner, A.; Garbe, C.; Meier, F.] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Schmitz, J.; Schmid, A.; Calaminus, C.; Pichler, B. J.] Univ Tubingen, Lab Preclin Imaging & Imaging Technol, Tubingen, Germany. [Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Honegger, J. B.] Univ Tubingen, Dept Neurosurg, Tubingen, Germany. [Dummer, R.] Univ Zuerich, Dept Dermatol, Zurich, Switzerland. [Tabatabai, G.] Univ Zuerich, Dept Neurol, Zurich, Switzerland. [Quintanilla-Fend, L.] Univ Tubingen, Inst Pathol, Tubingen, Germany. RI Pichler, Bernd/B-4483-2012 NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD JUL PY 2013 VL 11 SU 7 SI SI BP 5 EP 5 PG 1 WC Dermatology SC Dermatology GA 202OO UT WOS:000323227600015 ER PT J AU Heppt, MV Wang, JX Hristova, DM Wei, Z Berking, C Besch, R Rauscher Iiird, FJ Fisher, DE Herlyn, M Fukunaga-Kalabis, M AF Heppt, M., V Wang, J. X. Hristova, D. M. Wei, Z. Berking, C. Besch, R. Rauscher Iiird, F. J. Fisher, D. E. Herlyn, M. Fukunaga-Kalabis, M. TI MSX1 Contributes to Melanocyte Reprogramming and Progression of Melanoma SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Heppt, M., V; Wang, J. X.; Hristova, D. M.; Herlyn, M.; Fukunaga-Kalabis, M.] Wistar Inst Anat & Biol, Melanoma Res Ctr, Philadelphia, PA 19104 USA. [Wei, Z.] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA. [Berking, C.; Besch, R.] Univ Munich, Dept Dermatol, D-80539 Munich, Germany. [Rauscher Iiird, F. J.] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA. [Fisher, D. E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD JUL PY 2013 VL 11 SU 7 SI SI BP 15 EP 15 PG 1 WC Dermatology SC Dermatology GA 202OO UT WOS:000323227600043 ER PT J AU Fedorenko, I Rebecca, V Paraiso, K Wood, E Gibney, G Koomen, J Messina, J Wargo, J Flahery, K Smalley, K AF Fedorenko, I Rebecca, V Paraiso, K. Wood, E. Gibney, G. Koomen, J. Messina, J. Wargo, J. Flahery, K. Smalley, K. TI Overcoming Microenvironment-Mediated Drug Resistance in Melanoma SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Fedorenko, I] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Rebecca, V; Paraiso, K.] Univ S Florida, H Lee Moffitt Canc Ctr, Canc Biol PhD Program, Tampa, FL 33682 USA. [Wood, E.; Koomen, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Prote Core Facil, Tampa, FL 33682 USA. [Gibney, G.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Med Oncol, Tampa, FL 33682 USA. [Messina, J.] Univ S Florida, Coll Med, Dept Pathol & Cell Biol, Tampa, FL USA. [Wargo, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Flahery, K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Smalley, K.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Mol Oncol, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD JUL PY 2013 VL 11 SU 7 SI SI BP 43 EP 43 PG 1 WC Dermatology SC Dermatology GA 202OO UT WOS:000323227600131 ER PT J AU Hayashi, M Tanemura, A Matsuda, K Hosokawa, K Izumi, M Ohara, K Mihm, MC Katayama, I AF Hayashi, M. Tanemura, A. Matsuda, K. Hosokawa, K. Izumi, M. Ohara, K. Mihm, M. C. Katayama, I TI A Rare Case of Pigmented Epithelioid Melanocytoma with Pseudo Metastasis to Draining Lymph Node in Atopic Dermatitis SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Hayashi, M.; Tanemura, A.; Matsuda, K.; Hosokawa, K.; Katayama, I] Osaka Univ, Grad Sch Med, Suita, Osaka, Japan. [Izumi, M.] Tokyo Med Univ, Tokyo 1608402, Japan. [Ohara, K.] Toranomon Gen Hosp, Tokyo, Japan. [Mihm, M. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mihm, M. C.] Harvard Univ, Sch Med, Cambridge, MA 02138 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 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD JUL PY 2013 VL 11 SU 7 SI SI BP 85 EP 86 PG 2 WC Dermatology SC Dermatology GA 202OO UT WOS:000323227600264 ER PT J AU Parot, V Lim, D Gonzalez, G Traverso, G Nishioka, NS Vakoc, BJ Durr, NJ AF Parot, Vicente Lim, Daryl Gonzalez, German Traverso, Giovanni Nishioka, Norman S. Vakoc, Benjamin J. Durr, Nicholas J. TI Photometric stereo endoscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE three-dimensions; endoscopy; tissues; computer vision; stereoscopy ID RANDOMIZED CONTROLLED-TRIAL; COLORECTAL-CANCER; COLONOSCOPY; ADENOMAS; POLYPS AB While color video endoscopy has enabled wide-field examination of the gastrointestinal tract, it often misses or incorrectly classifies lesions. Many of these missed lesions exhibit characteristic three-dimensional surface topographies. An endoscopic system that adds topographical measurements to conventional color imagery could therefore increase lesion detection and improve classification accuracy. We introduce photometric stereo endoscopy (PSE), a technique which allows high spatial frequency components of surface topography to be acquired simultaneously with conventional two-dimensional color imagery. We implement this technique in an endoscopic form factor and demonstrate that it can acquire the topography of small features with complex geometries and heterogeneous optical properties. PSE imaging of ex vivo human gastrointestinal tissue shows that surface topography measurements enable differentiation of abnormal shapes from surrounding normal tissue. Together, these results confirm that the topographical measurements can be obtained with relatively simple hardware in an endoscopic form factor, and suggest the potential of PSE to improve lesion detection and classification in gastrointestinal imaging. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Parot, Vicente; Lim, Daryl; Gonzalez, German; Durr, Nicholas J.] MIT, Madrid MIT M Vis Consortium, Cambridge, MA 02139 USA. [Parot, Vicente; Lim, Daryl; Gonzalez, German; Vakoc, Benjamin J.; Durr, Nicholas J.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Parot, Vicente; Lim, Daryl; Gonzalez, German; Vakoc, Benjamin J.; Durr, Nicholas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Traverso, Giovanni; Nishioka, Norman S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Traverso, Giovanni] MIT, Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USA. RP Durr, NJ (reprint author), MIT, Madrid MIT M Vis Consortium, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ndurr@mit.edu OI , /0000-0002-9261-6667 FU Comunidad de Madrid through the Madrid-MIT M+Vision Consortium FX This work has been financially supported by the Comunidad de Madrid through the Madrid-MIT M+Vision Consortium. We thank the M+Vision IDEA3 faculty panel for their assistance in developing this project. We also thank Dr. Fernando Bermejo, Dr. Victor Defarges, and Dr. Gema De La Poza for their clinical advice. We are indebted to Mrs. Jennifer Patel from the MGH Pathology Department for technical assistance with human tissue specimens. We would like to thank Pentax for providing the endoscopic equipment used for this research, and in particular Mr. Mike Fina for facilitating access to the equipment. NR 20 TC 7 Z9 7 U1 0 U2 11 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 2013 VL 18 IS 7 AR 076017 DI 10.1117/1.JBO.18.7.076017 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 199YB UT WOS:000323030400025 PM 23864015 ER PT J AU Pestana, N Mortensen, LJ Runnels, JM Vickers, D Murthy, SK Lin, CP Niedre, M AF Pestana, Noah Mortensen, Luke J. Runnels, Judith M. Vickers, Dwayne Murthy, Shashi K. Lin, Charles P. Niedre, Mark TI Improved diffuse fluorescence flow cytometer prototype for high sensitivity detection of rare circulating cells in vivo SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE in vivo; flow cytometry; fluorescence; diffuse light; mesenchymal stem cells ID CANCER; TOMOGRAPHY; METASTASIS AB Detection and enumeration of rare circulating cells in mice are important problems in many areas of preclinical biomedical research. Recently, we developed a new method termed "diffuse fluorescence flow cytometry" (DFFC) that uses diffuse photons to increase the blood sampling volume and sensitivity versus existing in vivo flow cytometry methods. In this work, we describe a new DFFC prototype with approximately an order-of-magnitude improvement in sensitivity compared to our previous work. This sensitivity improvement is enabled by a number of technical innovations, which include a method for the removal of motion artifacts (allowing interrogation of mouse hindlegs that was less optically attenuating versus the tail) and improved collection optics and signal pre-amplification. We validated our system first in limb mimicking optical flow phantoms with fluorescent microspheres and then in nude mice with fluorescently labeled mesenchymal stem cells at injected concentrations of 5 x 10(3) cells/mL. In combination, these improvements resulted in an overall cell counting sensitivity of about 1 cell/mL or better in vivo. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Pestana, Noah; Vickers, Dwayne; Murthy, Shashi K.; Niedre, Mark] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Mortensen, Luke J.; Runnels, Judith M.; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mortensen, Luke J.; Runnels, Judith M.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mortensen, Luke J.; Runnels, Judith M.; Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Niedre, M (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. EM mniedre@ece.neu.edu RI Vickers, Dwayne/I-5819-2012; OI Vickers, Dwayne/0000-0002-9218-7348; Mortensen, Luke/0000-0002-4331-4099 FU National Institutes of Health [5R21HL098750]; New Investigator award from the Massachusetts Life Sciences Center FX This work was funded with a grant from the National Institutes of Health (Grant No. 5R21HL098750) and from a New Investigator award from the Massachusetts Life Sciences Center. The authors wish to thank an anonymous reviewer for helpful comments in preparation of this manuscript. NR 16 TC 2 Z9 2 U1 0 U2 14 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 2013 VL 18 IS 7 AR 077002 DI 10.1117/1.JBO.18.7.077002 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 199YB UT WOS:000323030400035 PM 23831714 ER PT J AU Srinivasan, VJ Radhakrishnan, H AF Srinivasan, Vivek J. Radhakrishnan, Harsha TI Total average blood flow and angiography in the rat retina SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE retina; blood flow; red blood cells; angiography; optical coherence tomography; optic nerve head; ophthalmology ID OPTICAL COHERENCE TOMOGRAPHY; DOMAIN OCT; MICROANGIOGRAPHY; MICROVASCULATURE; GLAUCOMA; VESSELS; MICE AB High-resolution angiography and total average blood flow measurements in the rat retina using optical coherence tomography (OCT) are presented. Recently, an en face integration method, which does not require explicit calculation of vessel angles, was introduced to calculate blood flow using Doppler OCT. Using this method, rapid two-dimensional scanning has been shown to quantify pulsatile flow. However, high scanning speeds sacrifice transverse sampling density and may lead to biased velocity estimates. Alternatively, we show here that by using a volumetric scanning protocol that asynchronously samples a single vessel with respect to the heartbeat, it is possible to obtain accurate time-averaged flow measurements, even without explicit information about the pulsatile waveform. Total average retinal blood flows calculated using either arteries or veins are comparable, supporting the accuracy of this method. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Srinivasan, Vivek J.; Radhakrishnan, Harsha] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Radhakrishnan, Harsha] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Srinivasan, VJ (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 East Hlth Sci Dr,GBSF 2521, Davis, CA 95616 USA. EM vjsriniv@ucdavis.edu FU National Institutes of Health [R00NS067050, R01EB001954]; American Heart Association [IRG5440002]; Glaucoma Research Foundation FX We acknowledge support from the National Institutes of Health (R00NS067050, R01EB001954), the American Heart Association (IRG5440002), and the Glaucoma Research Foundation Catalyst for a Cure 2. We also thank Maria Angela Franceschini as well as Bruce Rosen for general support. NR 19 TC 9 Z9 10 U1 0 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 2013 VL 18 IS 7 AR 076025 DI 10.1117/1.JBO.18.7.076025 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 199YB UT WOS:000323030400033 PM 23887484 ER PT J AU Humphrey, KL Gilman, MD Little, BP Halpern, EF Abbott, GF Shepard, JAO Wu, CC AF Humphrey, Kathryn L. Gilman, Matthew D. Little, Brent P. Halpern, Elkan F. Abbott, Gerald F. Shepard, Jo-Anne O. Wu, Carol C. TI Radiographic Follow-up of Suspected Pneumonia: Survey of Society of Thoracic Radiology Membership SO JOURNAL OF THORACIC IMAGING LA English DT Article DE pneumonia follow-up; chest radiography; radiology recommendations ID COMMUNITY-ACQUIRED PNEUMONIA; MANAGEMENT; GUIDELINES; ADULTS; LUNG; DIAGNOSIS; NODULES AB Purpose: To examine the current radiographic follow-up recommendations of thoracic radiologists after detection of a new opacity, suspected to be pneumonia, on chest radiography.Materials and Methods: An anonymized, Institutional Review Board-approved, Internet-based survey was sent to the 735 members of the Society of Thoracic Radiology by e-mail. Questions focused on individual practices and institutional policies after radiographic detection of suspected pneumonia. Univariate and multivariable logistic regression analyses were used to evaluate for possible associations between recommendation practices and demographic variables, various clinical situations, and radiographic features.Results: Of the 209 radiologists who responded, 42% always recommended follow-up radiographs for new opacities detected on chest radiographs, 55% sometimes recommended follow-up, and 2% never recommended follow-up. Univariate logistic regression analysis revealed that years in practice (P=0.0043) and number of outpatient posterior-anterior and lateral chest radiographs interpreted per week (P=0.027) were significant predictors of the recommendation practices. In addition, the multivariable logistic regression analysis pointed to the type of practice (academic vs. private) as an additional independent predictor of the recommendation practices (P=0.0294). The recommendations of those radiologists recommending follow-up sometimes were most often influenced by the radiographic appearance of the opacity and patient age. Only 4% reported an institutional policy.Conclusions: The majority of responding radiologists recommended follow-up on a case-by-case basis, influenced by multiple factors. Only a small minority reported a standardized practice at their institution. This lack of consistency demonstrates the need for a uniform, evidence-based approach. C1 [Humphrey, Kathryn L.; Gilman, Matthew D.; Halpern, Elkan F.; Abbott, Gerald F.; Shepard, Jo-Anne O.; Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Little, Brent P.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. RP Humphrey, KL (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM klhumphrey@partners.org NR 12 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JUL PY 2013 VL 28 IS 4 BP 240 EP 243 DI 10.1097/RTI.0b013e3182776c5e PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 202MS UT WOS:000323221800008 PM 23222200 ER PT J AU Fairchild, AH Chick, JFB Dorton, BJ AF Fairchild, Alexandra Holmsen Chick, Jeffrey Forris Beecham Dorton, Benjamin James TI Identity crisis The patient's abdominal discomfort stemmed from a treacherous event SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID OVARIAN VEIN-THROMBOSIS C1 [Fairchild, Alexandra Holmsen; Chick, Jeffrey Forris Beecham] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Dorton, Benjamin James] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fairchild, AH (reprint author), Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 6 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2013 VL 209 IS 1 AR 70.e1 DI 10.1016/j.ajog.2013.02.038 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 181XL UT WOS:000321703700026 ER PT J AU Terry, AR Barker, FG Leffert, L Bateman, BT Souter, I Plotkin, SR AF Terry, Anna R. Barker, Fred G., II Leffert, Lisa Bateman, Brian T. Souter, Irene Plotkin, Scott R. TI Neurofibromatosis type 1 and pregnancy complications: a population-based study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean section; epidemiology; intrauterine growth restriction; neurofibromatosis; preeclampsia ID CARDIOVASCULAR-DISEASE; MATERNAL MORTALITY; UNITED-STATES; ABNORMALITIES; PREVENTION; MORBIDITY; RISK; LIFE; NF1 AB OBJECTIVE: The objective of the study was to determine whether vascular and other complications are more common in pregnant women with neurofibromatosis type 1 (NF1). STUDY DESIGN: We performed a population-based retrospective cohort study using the US Nationwide Inpatient Sample, 1988-2009, defining a cohort of pregnancy-related hospitalizations with an associated diagnosis of NF1 and comparing it with the control group not associated with NF1. Multivariable logistic regression was used to adjust for suspected confounders. RESULTS: Among 19 million pregnancy-related admissions between 1988 and 2009, we identified 1553 associated with NF1 (prevalence 0.008%). A diagnosis of NF1 in delivering mothers was associated with gestational hypertension (adjusted odds ratio [AOR], 1.6, 95% confidence interval [CI], 1.2-2.0), preeclampsia (AOR, 2.8, 95% CI, 2.3-3.4), intrauterine growth restriction (AOR, 4.6, 95% CI, 3.7-5.6), cerebrovascular disease (OR, 8.1, 95% CI, 2.6-25.4), preterm labor (AOR, 1.6, 95% CI, 1.4-1.9), and cesarean delivery (AOR, 2.0, 95% CI, 1.8-2.3). Women with NF1 were not significantly more likely to have deep venous thrombosis/pulmonary embolism, acute cardiac events, or stillbirth or to die during their hospitalizations compared with the general obstetric population. CONCLUSION: NF1 was associated with increased maternal morbidity in pregnancy (including hypertensive and cerebrovascular complications) but not increased maternal mortality. Obstetricians should be aware of the potential for increased antenatal and peripartum complications among women with NF1. C1 [Terry, Anna R.; Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Leffert, Lisa; Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Souter, Irene] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Terry, AR (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, White 502, Boston, MA 02114 USA. EM arterry1977@gmail.com FU John and Cyndy Leahy Fellowship Fund; Massachusetts General Hospital; Massachusetts General Hospital Neurosurgical Service FX The purchase of databases and computing supplies was supported by the John and Cyndy Leahy Fellowship Fund. The corresponding author is grateful to Dr Robert Martuza of Massachusetts General Hospital and the Massachusetts General Hospital Neurosurgical Service for generous financial support of relevant coursework at the Harvard School of Public Health. The authors also thank Vanessa Merker, BS, of Massachusetts General Hospital, for assistance editing this manuscript. NR 25 TC 3 Z9 3 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2013 VL 209 IS 1 AR 46.e1 DI 10.1016/j.ajog.2013.03.029 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 181XL UT WOS:000321703700016 PM 23535241 ER PT J AU Sallstrom, J Peuckert, C Gao, X Larsson, E Nilsson, A Jensen, BL Onozato, ML Persson, AEG Kullander, K Carlstrom, M AF Sallstrom, Johan Peuckert, Christiane Gao, Xiang Larsson, Erik Nilsson, Anders Jensen, Boye L. Onozato, Maristela L. Persson, A. Erik G. Kullander, Klas Carlstrom, Mattias TI Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ephrin; gene modified mice; human disorder; receptor; ureteral obstruction ID SALT-SENSITIVE HYPERTENSION; NITRIC-OXIDE DEFICIENCY; OBSTRUCTIVE NEPHROPATHY; VESICOURETERAL REFLUX; RATS; MICE; ABNORMALITIES; PHYSIOLOGY; KIDNEY AB Experimental hydronephrosis induced by partial ureteral obstruction at 3 wk of age causes hypertension and renal impairment in adult rats and mice. Signaling by Ephrin receptors (Eph) and their ligands (ephrins) importantly regulates embryonic development. Genetically modified mice, where the cytoplasmic domain of the EphA4 receptor has been substituted by enhanced green fluorescent protein (EphA4(gf/gf)), develop spontaneous hydronephrosis and provide a model for further studies of the disorder. The present study aimed to determine if animals with congenital hydronephrosis develop hypertension and renal injuries, similar to that of experimental hydronephrosis. Ultrasound and Doppler techniques were used to visualize renal impairment in the adult mice. Telemetric blood pressure measurements were performed in EphA4(gf/gf) mice and littermate controls (EphA4(+/+)) during normal (0.7% NaCl)- and high (4% NaCl)-sodium conditions. Renal excretion, renal plasma flow, and glomerular filtration were studied, and histology and morphology of the kidneys and ureters were performed. EphA4(gf/gf) mice developed variable degrees of hydronephrosis that correlated with their blood pressure level. In contrast to EphA4(+/+), the EphA4(gf/gf) mice displayed salt-sensitive hypertension, reduced urine concentrating ability, reduced renal plasma flow, and lower glomerular filtration rate. Kidneys from EphA4(gf/gf) mice showed increased renal injuries, as evidenced by fibrosis, inflammation, and glomerular and tubular changes. In conclusion, congenital hydronephrosis causes hypertension and renal damage, similar to that observed in experimentally induced hydronephrosis. This study further reinforces the supposed causal link between hydronephrosis and later development of hypertension in humans. C1 [Sallstrom, Johan; Gao, Xiang; Persson, A. Erik G.; Carlstrom, Mattias] Uppsala Univ, Deptartment Med Cell Biol, Uppsala, Sweden. [Sallstrom, Johan; Carlstrom, Mattias] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. [Peuckert, Christiane; Gao, Xiang; Kullander, Klas] Uppsala Univ, Dept Neurosci, Uppsala, Sweden. [Larsson, Erik] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Nilsson, Anders] Uppsala Univ, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden. [Jensen, Boye L.] Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, Odense, Denmark. [Onozato, Maristela L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Carlstrom, M (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden. EM mattias.carlstrom@ki.se RI Peuckert, Christiane/I-5958-2016 OI Peuckert, Christiane/0000-0002-5973-1241 FU Swedish Research Council [K2009-64X-03522-38-2, K2012-99X-21971-01-3, K2004-32P-15230, K2005-33X-15327]; Wallenberg Foundation; Wallenberg Consortium North; Swedish Heart and Lung Foundation [20110589, 20100183]; Jeanssons Foundation; Ingabritt and Arne Lundberg Foundation; European Union through European Regional Development Fund; Archimedes Foundation; Fritz Thyssen Foundation [GARBK6588] FX This study was financially supported by the Swedish Research Council (K2012-99X-21971-01-3, K2009-64X-03522-38-2, K2004-32P-15230, and K2005-33X-15327), Wallenberg Foundation, Wallenberg Consortium North, Swedish Heart and Lung Foundation (20110589 and 20100183), Jeanssons Foundation, Ingabritt and Arne Lundberg Foundation, European Union through European Regional Development Fund, Archimedes Foundation, Fritz Thyssen Foundation, and GARBK6588. NR 35 TC 7 Z9 7 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2013 VL 305 IS 1 BP F71 EP F79 DI 10.1152/ajprenal.00694.2012 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 174YG UT WOS:000321193500009 PM 23637205 ER PT J AU Lee, RJ Cohen, NA AF Lee, Robert J. Cohen, Noam A. TI The emerging role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ANTIMICROBIAL ACTIVITY; CHRONIC SINUSITIS; EPITHELIAL-CELLS; CYSTIC-FIBROSIS; INNATE IMMUNITY; NITRIC-OXIDE; BIOFILMS; DISEASE; SYSTEMS; POLYPS AB Background: Maintaining a clean upper respiratory tract requires efficient detection of pathogenic bacteria so that the airway mucosa can mount proper defenses to neutralize and clear the offending microbes. Bitter taste receptors (T2Rs) may play a critical role in this process. T2Rs were originally identified in taste cells of the tongue, where they protect against the ingestion of toxic plant and/or bacterial products. However, T2Rs are also expressed in extragustatory tissue including the airways. One specific T2R isoform, T2R38, was recently shown to be expressed in cilia of sinonasal epithelial cells, suggesting that respiratory cilia may function as a chemosensory organelle, possibly to detect bacterial presence in the airway. T2R38 is encoded by the TAS2R38 gene, which has several common genetic polymorphisms that result in altered receptor functionality. Genetic variation in T2R38 may thus contribute to individual differences in susceptibility to upper airway infection. This study provides an overview of our current knowledge of T2R38 function in sinonasal defense and the implications for patients with chronic rhinosinusitis (CRS). Methods: A literature review was performed of the current knowledge of the bitter taste receptor T2R38 in sinonasal physiology and CRS patient outcomes. Results: Basic science research has indicated that the T2R38 receptor is activated by acyl-homoserine lactone (AHL) molecules secreted by gram-negative bacteria, including Pseudomonas aeruginosa. In sinonasal epithelial cells T2R38 stimulates an increase in nitric oxide production that increases mucociliary clearance and directly kills bacteria. Recent clinical studies have also found clinical correlations of TAS2R38 genotype with susceptibility to gram-negative upper respiratory infection as well as necessity for surgical intervention in CRS management. Conclusion: T2R38 appears to be an important mediator of sinonasal epithelial defense, but further study is needed to more clearly determine how TAS2R38 genotype affects patient outcomes in CRS and other upper airway diseases. C1 [Lee, Robert J.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM noam.cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU Flight Attendants Medical Research Institute [082478] FX NA Cohen's research in the laboratory was funded by a grant from the Flight Attendants Medical Research Institute (082478) and a philanthropic contribution from the RLG Foundation, Inc. The remaining author has no conflicts of interest to declare pertaining to this article NR 32 TC 21 Z9 21 U1 2 U2 24 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JUL-AUG PY 2013 VL 27 IS 4 BP 283 EP 286 DI 10.2500/ajra.2013.27.3911 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 193HK UT WOS:000322549600013 PM 23883809 ER PT J AU Scarpati, GDV Fusciello, C Sabbatino, F Ferrone, S Caponigro, F Perri, F Carlomagno, C Pepe, S AF Scarpati, Giuseppina Della Vittoria Fusciello, Celeste Sabbatino, Francesco Ferrone, Soldano Caponigro, Francesco Perri, Francesco Carlomagno, Chiara Pepe, Stefano TI Multidisciplinary Approach to Patient with Malignant Melanoma SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Melanoma; immunotherapy; B-RAF inibithors; chemotherapy ID PRIMARY CUTANEOUS MELANOMA; PHASE-II TRIAL; DOSE RECOMBINANT INTERLEUKIN-2; COOPERATIVE-ONCOLOGY-GROUP; STAGE-IV MELANOMA; LYMPH-NODE BIOPSY; TUMOR-INFILTRATING LYMPHOCYTES; VERTICAL GROWTH-PHASE; BRAF V600E MUTATION; REGULATORY T-CELLS AB The incidence of melanoma is rapidly increasing worldwide and the prognosis of patients with metastatic disease is still poor, with a median survival of 8-9 months and a 3-year overall survival (OS) rate less than 15% [1,2]. A complete surgical excision is the main treatment for primary cutaneous melanoma [3], but controversies about the extension of excision margins still remain [4]. Sentinel lymph node biopsy (SLNB) provides important prognostic and staging data by the identification of regional node-negative patients who would not benefit from a complete nodal dissection. However, there is no consensus in the definition of melanoma thickness to enforce the execution of the SLNB [5]. To date, Interferon-alpha (IFN-alpha) is the only approved adjuvant treatment after surgical excision of high-risk melanoma, but its indication remains still controversial [2,6]. C1 [Scarpati, Giuseppina Della Vittoria; Fusciello, Celeste; Pepe, Stefano] Univ Salerno, Dept Med, I-84100 Salerno, Italy. [Scarpati, Giuseppina Della Vittoria; Fusciello, Celeste; Pepe, Stefano] San Giovanni Dio & Ruggi Aragona Hosp, Div Oncol, Salerno, Italy. [Fusciello, Celeste; Carlomagno, Chiara] Univ Neaples Federico II, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy. [Sabbatino, Francesco; Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Caponigro, Francesco; Perri, Francesco] Fdn G Pascale, Ist Tumori Napoli, Head & Neck Oncol Unit, Naples, Italy. RP Pepe, S (reprint author), Univ Salerno, Dept Med, I-84100 Salerno, Italy. EM stepepe@unisa.it RI Sabbatino, Francesco/F-4992-2014; ionna, Franco/K-4564-2016 OI Sabbatino, Francesco/0000-0001-6431-8278; ionna, Franco/0000-0002-0512-274X NR 151 TC 1 Z9 1 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD JUL PY 2013 VL 13 IS 6 BP 887 EP 900 PG 14 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 190EB UT WOS:000322320400007 PM 23272971 ER PT J AU Dworkin, SL Grabe, S Lu, T Hatcher, A Kwena, Z Bukusi, E Mwaura-Muiru, E AF Dworkin, Shari L. Grabe, Shelly Lu, Tiffany Hatcher, Abbey Kwena, Zachary Bukusi, Elizabeth Mwaura-Muiru, Esther TI Property Rights Violations as a Structural Driver of Women's HIV Risks: A Qualitative Study in Nyanza and Western Provinces, Kenya SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE HIV prevention and treatment; Women; Sexual risk; Property ownership; Structural interventions; Kenya ID INTIMATE-PARTNER VIOLENCE; RURAL CREDIT PROGRAMS; TO-CHILD TRANSMISSION; DAR-ES-SALAAM; SOUTH-AFRICA; SEROSTATUS DISCLOSURE; PREGNANT-WOMEN; PREVENTION; GENDER; EMPOWERMENT AB While access to and control over assets can minimize women's HIV risk, little is known about the processes through which property rights violations increase the sexual transmission of HIV. The current study focused on two rural areas in Nyanza and Western Province, Kenya where HIV prevalence was high (23.8-33 %) and property rights violations were common. The current work drew on in-depth interview data collected from 50 individuals involved in the development and implementation of a community-led land and property rights program. The program was designed to respond to property rights violations, prevent disinheritance and asset stripping, and reduce HIV risk among women. In our findings, we detailed the social and economic mechanisms through which a loss of property rights was perceived to influence primary and secondary prevention of HIV. These included: loss of income, loss of livelihood and shelter, and migration to slums, markets, or beaches where the exchange of sex for food, money, shelter, clothing, or other goods was common. We also examined the perceived influence of cultural practices, such as wife inheritance, on HIV risk. In the conclusions, we made recommendations for future research in the science-base focused on the development of property ownership as a structural HIV prevention and treatment intervention. C1 [Dworkin, Shari L.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Dworkin, Shari L.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94118 USA. [Grabe, Shelly] Univ Calif Santa Cruz, Dept Psychol, Santa Cruz, CA 95064 USA. [Lu, Tiffany] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hatcher, Abbey] Univ Calif San Francisco, Bixby Ctr Reprod Hlth, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94118 USA. [Kwena, Zachary; Bukusi, Elizabeth] Kenya Med Res Inst KEMRI, Ctr Microbiol Res, Kisumu, Kenya. [Mwaura-Muiru, Esther] GROOTS Kenya, Nairobi, Kenya. RP Dworkin, SL (reprint author), Univ Calif San Francisco, 3333 Calif St,LHTS 455, San Francisco, CA 94118 USA. EM shari.dworkin@ucsf.edu RI Hatcher, Abigail/G-9128-2011 OI Hatcher, Abigail/0000-0002-4150-1405 FU NIAID NIH HHS [P30-AI027763, P30 AI027763] NR 77 TC 13 Z9 13 U1 1 U2 16 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD JUL PY 2013 VL 42 IS 5 BP 703 EP 713 DI 10.1007/s10508-012-0024-6 PG 11 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 189FT UT WOS:000322253400008 PM 23179234 ER PT J AU Kook, SH Cho, JS Morrison, A Wiener, E Lee, SB Scadden, D Lee, BC AF Kook, S. H. Cho, J. S. Morrison, A. Wiener, E. Lee, S. B. Scadden, D. Lee, B-C TI The purinergic P2Y(14) receptor axis is a molecular determinant for organism survival under in utero radiation toxicity SO CELL DEATH & DISEASE LA English DT Article DE in utero radiation; purinergic receptors; embryo ID HEMATOPOIETIC STEM-CELLS; CELLULAR-RESPONSE; UDP-GLUCOSE; MICE; INJURY; GAMMA; IRRADIATION; SENESCENCE; DAMAGE; BRAIN AB In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y(14), confers potent resistance to in utero radiation. Intriguingly, a putative P2Y(14) receptor ligand, UDP-glucose, phenocopies the effect of P2Y(14) deficiency. These data indicate that P2Y(14) is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy. C1 [Kook, S. H.; Cho, J. S.; Lee, B-C] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Div Hematol & Oncol,Dept Med, Pittsburgh, PA 15213 USA. [Morrison, A.] GlaxoSmithKline, PTS, Stevenage SG1 2NY, Herts, England. [Wiener, E.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. [Lee, S. B.] Tulane Univ, Sch Med, Dept Pathol & Lab Med, New Orleans, LA 70112 USA. [Scadden, D.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scadden, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Scadden, D.] Harvard Stem Cell Inst, Cambridge, MA USA. [Scadden, D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Lee, BC (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Div Hematol & Oncol,Dept Med, 5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM leeb4@upmc.edu OI Cho, Joonseok/0000-0001-7268-5748 FU Department of Defense [W81XWH-09-1-0364]; NIH [P30CA047904] FX We thank Drs. Seong-Gi Kim and Saiful Huq for the helpful discussions and suggestions. This study was supported in part by research funding from the Department of Defense (W81XWH-09-1-0364) to B-C Lee. This project used the UPCI flow cytometry and animal facility, which were supported in part by the P30CA047904 award from NIH. NR 27 TC 3 Z9 3 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD JUL PY 2013 VL 4 AR e703 DI 10.1038/cddis.2013.218 PG 8 WC Cell Biology SC Cell Biology GA 192US UT WOS:000322512100004 PM 23828566 ER PT J AU Nguyen, HQ Fan, VS Herting, J Lee, J Fu, M Chen, ZJ Borson, S Kohen, R Matute-Bello, G Pagalilauan, G Adams, SG AF Nguyen, Huong Q. Fan, Vincent S. Herting, Jerald Lee, Jungeun Fu, Musetta Chen, Zijing Borson, Soo Kohen, Ruth Matute-Bello, Gustavo Pagalilauan, Genevieve Adams, Sandra G. TI Patients With COPD With Higher Levels of Anxiety Are More Physically Active SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; POPULATION-BASED COHORT; QUALITY-OF-LIFE; FUNCTIONAL STATUS; HEALTH OUTCOMES; DEPRESSION; DYSPNEA; REHABILITATION; MORTALITY; RISK AB Background: Physical activity (PA) has been found to be an excellent predictor of mortality beyond traditional measures in COPD. We aimed to determine the association between depression and anxiety with accelerometry-based PA in patients with COPD. Methods: We performed a cross-sectional analysis of baseline data from 148 stable patients with COPD enrolled in an ongoing, longitudinal, observational study. We measured PA (total daily step count) with a Stepwatch Activity Monitor over 7 days, depression and anxiety with the Hospital Anxiety and Depression Scales (HADSs), dyspnea with the Shortness of Breath Questionnaire, and functional capacity with the 6-min walk test. Results: Increased anxiety was associated with higher levels of PA such that for every one-point increase in the HADS-Anxiety score there was a corresponding increase of 288 step counts per day (beta = 288 steps, P < .001), after adjusting for all other variables. Higher levels of depressive symptoms were associated with lower PA (beta = -176 steps, P = .02) only when anxiety was in the model. The interaction term for anxiety and depression approached significance (beta = 26, P = .10), suggesting that higher levels of anxiety mitigate the negative effects of depression on PA. Conclusions: The increased PA associated with anxiety in COPD is, to our knowledge, a novel finding. However, it is unclear whether anxious patients with COPD are more restless, and use increased psychomotor activity as a coping mechanism, or whether those with COPD who push themselves to be more physically active experience more anxiety symptoms. Future studies should evaluate for anxiety and PA to better inform how to improve clinical outcomes. Trial Registry: Clinicaltrials.gov; No.: NCT01074515; URL: www.clinicaltrials.gov C1 [Nguyen, Huong Q.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Fan, Vincent S.; Herting, Jerald; Lee, Jungeun; Fu, Musetta; Chen, Zijing; Borson, Soo; Kohen, Ruth; Matute-Bello, Gustavo; Pagalilauan, Genevieve] Univ Washington, Seattle, WA 98195 USA. [Fan, Vincent S.] Puget Sound Vet Adm, Seattle, WA USA. [Adams, Sandra G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Adams, Sandra G.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Nguyen, HQ (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, 100 S Los Robles, Pasadena, CA 91101 USA. EM huong.q2.nguyen@kp.org FU US National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [5R01HL093146]; NIH National Center for Research Resources [UL1RR025014]; Department of Veterans Affairs FX This work was supported in part by grants from the US National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [5R01HL093146] and the NIH National Center for Research Resources [UL1RR025014]. Dr Fan has funding through the Department of Veterans Affairs. NR 43 TC 12 Z9 12 U1 1 U2 12 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2013 VL 144 IS 1 BP 145 EP 151 DI 10.1378/chest.12-1873 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 180OW UT WOS:000321605500024 PM 23370503 ER PT J AU Edwards, E Mischoulon, D Rapaport, M Stussman, B Weber, W AF Edwards, Emmeline Mischoulon, David Rapaport, Mark Stussman, Barbara Weber, Wendy TI Building an Evidence Base in Complementary and Integrative Healthcare for Child and Adolescent Psychiatry SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Complementary medicine; Integrative medicine; Mind and body; Natural products; Child and adolescent psychiatry; Manipulative therapies; CAM research; Epidemiology ID MAJOR DEPRESSIVE DISORDER; ALTERNATIVE MEDICINE; HERBAL MEDICINE; UNITED-STATES; THERAPY; AUTISM; ACUPUNCTURE; PATTERNS; MEDICATIONS; INFANTS AB Complementary and integrative strategies are widely used by families with children who have mental health diagnoses. The therapies used by these children include herbs, dietary supplements, massage, acupuncture, meditation, and naturopathy. The literature on efficacy of complementary and alternative approaches is of limited value, and studies are needed to test efficacy and safety. Interpretation of complementary and integrative health care studies for symptomatic management of mental health conditions is hampered by study design and methodological limitations. Well-designed, adequately powered, and suitably controlled clinical trials on promising complementary and integrative modalities are needed for children and adolescents with psychiatric conditions. C1 [Edwards, Emmeline; Weber, Wendy] NIH, Div Extramural Res, NCCAM, Bethesda, MD 20892 USA. [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Rapaport, Mark] Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA 30322 USA. [Stussman, Barbara] NIH, NCCAM, Bethesda, MD 20892 USA. RP Edwards, E (reprint author), NIH, Div Extramural Res, NCCAM, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM edwardse@mail.nih.gov FU Intramural NIH HHS [Z99 AT999999] NR 60 TC 0 Z9 0 U1 3 U2 16 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 JUL PY 2013 VL 22 IS 3 BP 509 EP + DI 10.1016/j.chc.2013.03.007 PG 22 WC Psychiatry SC Psychiatry GA 194BP UT WOS:000322606300009 PM 23806317 ER PT J AU Alperin, M Weinstein, M Kivnick, S Duong, TH Menefee, S AF Alperin, Marianna Weinstein, Milena Kivnick, Seth Duong, Thinh H. Menefee, Shawn TI A randomized trial of Prophylactic Uterosacral Ligament Suspension at the time of hysterectomy for Prevention of Vaginal Vault Prolapse (PULS): Design and methods SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Vaginal vault prolapse; Hysterectomy; Uterosacral ligament suspension; Colpopexy ID PELVIC ORGAN PROLAPSE; FLOOR DISORDERS; ENTEROCELE; REPAIR; WOMEN AB The primary aim of this randomized trial is to evaluate whether a standardized uterosacral ligament suspension colpopexy (USLSC), added to a planned hysterectomy for an indication other than pelvic organ prolapse (POP), decreases the rate of subsequent vaginal vault prolapse in women without preoperative symptomatic POP. Secondary aims include comparison of perioperative complications, urinary, bowel and sexual functions between subjects with and without concomitant USLSC. If shown to be beneficial, the cost-effectiveness of prophylactic USLSC at the time of hysterectomy will be evaluated. This trial will be performed at 4 centers across the United States. The data will be analyzed by the data-coordinating center of the Southern California Kaiser Permanente. Standardized questionnaires and objective measurements will be obtained. The patients and providers performing assessments are masked to treatment assignment The primary outcome, defined as absence of POP at/distal to the hymen on Pelvic Organ Prolapse Quantitative examination, will be determined 12 months post-operatively. Secondary outcomes include: no prolapse symptoms by questionnaires, and no treatment for POP besides the prophylactic study intervention. Additional follow-up occurs annually for a total of 5 years. Accrual is projected to take 3 years. Given cost and morbidity of surgical repair of post-hysterectomy prolapse, preventive strategies are of outmost importance. The risks and benefits of prophylactic USLSC have never been studied prospectively. This trial is designed to determine if USLSC is an appropriate clinical adjunct at the time of hysterectomy, with subsequent reduction of symptomatic POP. (C) 2013 Elsevier Inc. All rights reserved. C1 [Alperin, Marianna] Univ Calif San Diego, Dept Reprod Med, Div Female Pelv Med & Reconstruct Surg, La Jolla, CA 92093 USA. [Weinstein, Milena] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kivnick, Seth; Duong, Thinh H.] Kaiser Permanente, Dept Obstet & Gynecol, Los Angeles, CA USA. [Menefee, Shawn] Kaiser Permanente San Diego, Div Female Pelv Med & Reconstruct Surg, Dept Obstet & Gynecol, San Diego, CA USA. RP Alperin, M (reprint author), Univ Calif San Diego, Dept Reprod Med, Div FPMRS, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM malperin@ucsd.edu NR 20 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 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2013 VL 35 IS 2 BP 8 EP 12 DI 10.1016/j.cct.2013.04.001 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 193LI UT WOS:000322560900002 PM 23587538 ER PT J AU Ma, J Strub, P Lavori, PW Buist, S Camargo, CA Nadeau, KC Wilson, SR Xiao, L AF Ma, Jun Strub, Peg Lavori, Phillip W. Buist, Sonia Camargo, Carlos A., Jr. Nadeau, Kari C. Wilson, Sandra R. Xiao, Lan TI DASH for asthma: A pilot study of the DASH diet in not-well-controlled adult asthma SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE DASH; Dietary pattern; Asthma; Lung function; Asthma Control Questionnaire ID EXHALED NITRIC-OXIDE; RANDOMIZED CONTROLLED-TRIAL; MULTIPLE-PASS METHOD; OBSTRUCTIVE PULMONARY-DISEASE; HAND-HELD DEVICE; QUALITY-OF-LIFE; MEDITERRANEAN DIET; WEIGHT-LOSS; BLOOD-PRESSURE; CONFIDENCE-INTERVALS AB This pilot study aims to provide effect size confidence intervals, clinical trial and intervention feasibility data, and procedural materials for a full-scale randomized controlled trial that will determine the efficacy of Dietary Approaches to Stop Hypertension (DASH) as adjunct therapy to standard care for adults with uncontrolled asthma. The DASH diet encompasses foods (e.g., fresh fruit, vegetables, and nuts) and antioxidant nutrients (e.g., vitamins A, C, E, and zinc) with potential benefits for persons with asthma, but it is unknown whether the whole diet is beneficial. Participants (n = 90) will be randomized to receive usual care alone or combined with a DASH intervention consisting of 8 group and 3 individual sessions during the first 3 months, followed by at least monthly phone consultations for another 3 months. Follow-up assessments will occur at 3 and 6 months. The primary outcome measure is the 7-item juniper Asthma Control Questionnaire, a validated composite measure of daytime and nocturnal symptoms, activity limitations, rescue medication use, and percentage predicted forced expiratory volume in 1 second. We will explore changes in inflammatory markers important to asthma pathophysiology (e.g., fractional exhaled nitric oxide) and their potential to mediate the intervention effect on disease control. We will also conduct pre-specified subgroup analyses by genotype (e.g., polymorphisms on the glutathione S transferase gene) and phenotype (e.g., atopy, obesity). By evaluating a dietary pattern approach to improving asthma control, this study could advance the evidence base for refining clinical guidelines and public health recommendations regarding the role of dietary modifications in asthma management. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ma, Jun; Wilson, Sandra R.; Xiao, Lan] Palo Alto Med Fdn Res Inst, Dept Hlth Serv Res, Palo Alto, CA USA. [Ma, Jun] Stanford Univ, Dept Med, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Strub, Peg] San Francisco Med Ctr, Permanente Med Grp, Dept Allergy, San Francisco, CA USA. [Strub, Peg] San Francisco Med Ctr, Permanente Med Grp, Dept Asthma, San Francisco, CA USA. [Strub, Peg] San Francisco Med Ctr, Permanente Med Grp, Dept Immunol, San Francisco, CA USA. [Lavori, Phillip W.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Buist, Sonia] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Nadeau, Kari C.] Lucile Packard Childrens Hosp, Dept Pediat, Div Immunol & Allergy, Stanford, CA USA. [Nadeau, Kari C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Wilson, Sandra R.] Stanford Univ, Dept Med, Sch Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. RP Ma, J (reprint author), Palo Alto Med Fdn Res Inst, 795 El Camino Real, Palo Alto, CA USA. EM maj@pamfri.org FU National Heart, Lung and Blood Institute [R34 HL108753] FX The project described is supported by Award Number R34 HL108753 from the National Heart, Lung and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health. The authors wish to thank the study Data and Safety Monitoring Board members (William Haskell, PhD, Ware Kuschner, MD, and Manisha Desai, PhD). NR 122 TC 11 Z9 11 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2013 VL 35 IS 2 BP 55 EP 67 DI 10.1016/j.cct.2013.04.008 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 193LI UT WOS:000322560900007 PM 23648395 ER PT J AU Kangovi, S Barg, FK Carter, T Long, JA Shannon, R Grande, D AF Kangovi, Shreya Barg, Frances K. Carter, Tamala Long, Judith A. Shannon, Richard Grande, David TI Understanding Why Patients Of Low Socioeconomic Status Prefer Hospitals Over Ambulatory Care SO HEALTH AFFAIRS LA English DT Article ID MEDICAL-CARE; PREVENTABLE HOSPITALIZATIONS; EMERGENCY-DEPARTMENT; HEALTH-CARE; ACCESS; SATISFACTION; MORTALITY; EQUITY; TRENDS; IMPACT AB Patients with low socioeconomic status (SES) use more acute hospital care and less primary care than patients with high socioeconomic status. This low-value pattern of care use is harmful to these patients' health and costly to the health care system. Many current policy initiatives, such as the creation of accountable care organizations, aim to improve both health outcomes and the cost-effectiveness of health services. Achieving those goals requires understanding what drives low-value health care use. We conducted qualitative interviews with forty urban low-SES patients to explore why they prefer to use hospital care. They perceive it as less expensive, more accessible, and of higher quality than ambulatory care. Efforts that focus solely on improving the quality of hospital care to reduce readmissions could, paradoxically, increase hospital use. Two different profile types emerged from our research. Patients in Profile A (five or more acute care episodes in six months) reported social dysfunction and disability. Those in Profile B (fewer than five acute care episodes in six months) reported social stability but found accessing ambulatory care to be difficult. Interventions to improve outcomes and values need to take these differences into account. C1 [Kangovi, Shreya] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. [Kangovi, Shreya] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Barg, Frances K.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Long, Judith A.] Philadelphia Vet Affairs Ctr, Philadelphia, PA USA. [Shannon, Richard] Perelman Sch Med, Dept Med, Philadelphia, PA USA. [Grande, David] Perelman Sch Med, Philadelphia, PA USA. RP Kangovi, S (reprint author), Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. EM kangovi@upenn.edu FU Leonard Davis Institute of Health Economics at the University of Pennsylvania; HealthWell Foundation; National Human Genome Research Institute; Agency for Healthcare Research and Quality FX This study was supported by the Leonard Davis Institute of Health Economics at the University of Pennsylvania. David Grande has received honoraria from the Johns Hopkins University Continuing Medical Education Program; had a consultancy with the National Nursing Centers Consortium; and has received grant support from or has grants pending with the HealthWell Foundation, the National Human Genome Research Institute, and the Agency for Healthcare Research and Quality. Richard Shannon is the founder of a biotech company, Ventrigen; is a senior fellow at the Institute for Healthcare Improvement; and is on the scientific advisory boards for GlaxoSmithKline, Pfizer, Merck, and Value Capture. He also is a member of the board of directors of the American Board of Internal Medicine. The authors thank the Mixed Methods Research Laboratory at the University of Pennsylvania for its guidance and technical assistance with this study. NR 37 TC 59 Z9 59 U1 2 U2 31 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL PY 2013 VL 32 IS 7 BP 1196 EP 1203 DI 10.1377/hlthaff.2012.0825 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 187IS UT WOS:000322111200004 PM 23836734 ER PT J AU Pallin, DJ Allen, MB Espinola, JA Camargo, CA Bohan, JS AF Pallin, Daniel J. Allen, Matthew B. Espinola, Janice A. Camargo, Carlos A., Jr. Bohan, J. Stephen TI THE CARE SPAN Population Aging And Emergency Departments: Visits Will Not Increase, Lengths-Of-Stay And Hospitalizations Will SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; ELDERLY-PATIENTS; TRENDS; ADMISSIONS AB With US emergency care characterized as "at the breaking point," we studied how the aging of the US population would affect demand for emergency department (ED) services and hospitalizations in the coming decades. We applied current age-specific ED visit rates to the population structure anticipated by the Census Bureau to exist through 2050. Our results indicate that the aging of the population will not cause the number of ED visits to increase any more than would be expected from population growth. However, the data do predict increases in visit lengths and the likelihood of hospitalization. As a result, the aggregate amount of time patients spend in EDs nationwide will increase 10 percent faster than population growth. This means that ED capacity will have to increase by 10 percent, even without an increase in the number of visits. Hospital admissions from the ED will increase 23 percent faster than population growth, which will require hospitals to expand capacity faster than required by raw population growth alone. C1 [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Allen, Matthew B.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Bohan, J. Stephen] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Brigham and Women's Hospital Department of Emergency Medicine FX A version of this article was presented at the Society of Academic Emergency Medicine, Atlanta, Georgia, May 16, 2013. This study received support from a seed grant from the Brigham and Women's Hospital Department of Emergency Medicine. NR 28 TC 12 Z9 12 U1 0 U2 7 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL PY 2013 VL 32 IS 7 BP 1306 EP 1312 DI 10.1377/hlthaff.2012.0951 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 187IS UT WOS:000322111200018 PM 23836748 ER PT J AU Vaduganathan, M Fonarow, GC AF Vaduganathan, Muthiah Fonarow, Gregg C. TI Epidemiology of Hospitalized Heart Failure Differences and Similarities Between Patients with Reduced versus Preserved Ejection Fraction SO HEART FAILURE CLINICS LA English DT Article DE Acute heart failure; Preserved ejection fraction; Epidemiology; Outcomes ID SYSTOLIC FUNCTION; SUBSEQUENT MORTALITY; NATIONAL TRENDS; I-PRESERVE; OUTCOMES; TRIAL; REGISTRY; PROGRAM; RATES; REHOSPITALIZATION AB Annually, more than 1 million patients are hospitalized for heart failure (HF), translating to high healthcare utilization and cost burden. Among patients with hospitalized HF (HHF), approximately 50% have HF with preserved ejection fraction (HFpEF) and 50% have HF with reduced ejection fraction (HFrEF), with the proportion of patients with HFpEF increasing with time. This article defines the epidemiologic landscape of patients with HHF, comparing and contrasting those with HFpEF and HFrEF, and identifies key areas that require further investigation. More complete characterization of these populations may be the first step to developing effective therapies. C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, Los Angeles, CA 90095 USA. RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, 10833 LeConte Ave,Room A2-237 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu FU Agency for Healthcare Research and Quality FX No relevant relationships to disclose (M. Vaduganathan). Research support, Agency for Healthcare Research and Quality (significant); Consultant, Medtronic (modest) and Novartis (significant) (G.C. Fonarow). NR 35 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2013 VL 9 IS 3 BP 271 EP + DI 10.1016/j.hfc.2013.04.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191NX UT WOS:000322421000003 PM 23809413 ER PT J AU Vaduganathan, M Marti, CN Georgiopoulou, VV Kalogeropoulos, AP Butler, J AF Vaduganathan, Muthiah Marti, Catherine N. Georgiopoulou, Vasiliki V. Kalogeropoulos, Andreas P. Butler, Javed TI Classification of Patients Hospitalized for Heart Failure SO HEART FAILURE CLINICS LA English DT Article DE Acute heart failure; Classification; Management; Outcomes ID REDUCED EJECTION FRACTION; PRESERVED SYSTOLIC FUNCTION; NATIONAL REGISTRY ADHERE; EVEREST TRIAL; VASOPRESSIN ANTAGONISM; CLINICAL CHARACTERISTICS; MYOCARDIAL-INFARCTION; GUIDELINES PROGRAM; RANDOMIZED-TRIALS; BLOOD-PRESSURE AB Despite low inpatient mortality and effective symptomatic management, patients hospitalized for heart failure (HHF) experience high postdischarge mortality and rehospitalization rates. HHF represents a widely heterogeneous population with distinct clinical subsets that may require tailored management approaches. Despite this, however, HHF patients are almost uniformly managed with intravenous diuretics, with low uptake of new therapies during hospitalization. This article proposes a practical approach to classifying HHF patients that is focused on guiding individualized inpatient and postdischarge management. HHF is not a single disease but a manifestation of several cardiac and noncardiac processes and thus should be approached as such. C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Marti, Catherine N.; Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Butler, Javed] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Div Cardiol, Atlanta, GA 30322 USA. RP Butler, J (reprint author), Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Div Cardiol, 1462 Clifton Rd Northeast,Suite 504, Atlanta, GA 30322 USA. EM javed.butler@emory.edu RI Kalogeropoulos, Andreas/A-9494-2009 OI Kalogeropoulos, Andreas/0000-0002-1284-429X NR 43 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2013 VL 9 IS 3 BP 277 EP + DI 10.1016/j.hfc.2013.04.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191NX UT WOS:000322421000004 PM 23809414 ER PT J AU Gheorghiade, M Shah, AN Vaduganathan, M Butler, J Bonow, RO Rosano, GMC Taylor, S Kupfer, S Misselwitz, F Sharma, A Fonarow, GC AF Gheorghiade, Mihai Shah, Ami N. Vaduganathan, Muthiah Butler, Javed Bonow, Robert O. Rosano, Giuseppe M. C. Taylor, Scott Kupfer, Stuart Misselwitz, Frank Sharma, Arjun Fonarow, Gregg C. TI Recognizing Hospitalized Heart Failure as an Entity and Developing New Therapies to Improve Outcomes: Academics', Clinicians', Industry's, Regulators', and Payers' Perspectives SO HEART FAILURE CLINICS LA English DT Article DE Hospitalized heart failure; Heart failure; Postdischarge mortality ID RANDOMIZED CONTROLLED TRIAL; VASOPRESSIN ANTAGONISM; RECEPTOR ANTAGONIST; EVEREST EFFICACY; BG9719 CVT-124; RENAL-FUNCTION; TOLVAPTAN; DYSPNEA; STRATEGIES; NESIRITIDE AB Hospitalized heart failure (HHF) is associated with unacceptably high postdischarge mortality and rehospitalization rates. This heterogeneous group of patients, however, is still treated with standard, homogenous therapies that are not preventing their rapid deterioration. The costs associated with HHF have added demands from society, government, and payers to improve outcomes. With coordinated and committed efforts in the development of new therapies, improvements may be seen in outcomes for patients with HHF. This article summarizes concepts in developing therapies for HHF discussed during a multidisciplinary panel at the Heart Failure Society of America's Annual Scientific Meeting, September 2012. C1 [Gheorghiade, Mihai; Shah, Ami N.; Bonow, Robert O.] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Rosano, Giuseppe M. C.] IRCC San Raffaele, Div Cardiol, I-00163 Rome, Italy. [Taylor, Scott] Geisinger Hlth Syst, Ind Relat, Danville, PA 17822 USA. [Kupfer, Stuart] Takeda Global Res & Dev Ctr Inc, Deerfield, IL 60015 USA. [Misselwitz, Frank] Bayer HealthCare Pharmaceut, D-13353 Berlin, Germany. [Sharma, Arjun] Ontario Minist Hlth & Long Term Care, Toronto, ON, Canada. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA 90024 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 North Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu FU Medtronic; National Institutes of Health; Amgen; Novartis; Gambro FX M. Gheorghiade, MD: consultant to Abbott Laboratories, Astellas, Astra Zeneca, Bayer Schering Pharma AG, CorThera, Cytokinetics, DebioPharm SA, Errekappa Terapeutici, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, and Solvay Pharmaceuticals. J. Butler, MD, MPH: consultant to Cardio-MEMS, Bayer Health Care, Trevena, Ono Pharma, and Gambro; research support from Medtronic, National Institutes of Health, and Amgen. S. Taylor, RPh, MBA: employed by Geisinger Health System. S. Kupfer, MD: employed by Takeda Global Research and Development Center, Inc. F. Misselwitz, MD, PhD: employed by Bayer Health-Care. G.C. Fonarow, MD: research support from Medtronic, Novartis, and Gambro. A.N. Shah, MD; M. Vaduganathan, MD, MPH; G.M.C. Rosano, MD, PhD; and A. Sharma, MD: None. NR 41 TC 15 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 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2013 VL 9 IS 3 BP 285 EP + DI 10.1016/j.hfc.2013.05.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191NX UT WOS:000322421000005 PM 23809415 ER PT J AU Psotka, MA Teerlink, JR AF Psotka, Mitchell A. Teerlink, John R. TI Strategies to Prevent Postdischarge Adverse Events Among Hospitalized Patients with Heart Failure SO HEART FAILURE CLINICS LA English DT Article DE Hospitalized heart failure; Acute heart failure; Mortality; Readmission; Adverse events ID PRESERVED EJECTION FRACTION; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIALS; NATIONAL REGISTRY ADHERE; CARDIAC-RESYNCHRONIZATION THERAPY; OBSTRUCTIVE PULMONARY-DISEASE; LENGTH-OF-STAY; CLINICAL-OUTCOMES; MEDICARE BENEFICIARIES; VASOPRESSIN ANTAGONISM AB Hospitalizations for heart failure (HF) are increasing, and HF is the primary cause of readmission for all Medicare patients. Inpatient HF mortality is poor, but most morbidity and mortality occurs after hospital discharge. Readmissions attributable to HF persist or increase over time after discharge, and past HF admissions predict both readmission and mortality. The heightened risk of readmission dissipates slowly after discharge, suggesting that any intervention should be part of a lasting care package in the outpatient setting. Interventions that apply to multiple common medical comorbidities may be more likely to reduce overall adverse events. C1 [Psotka, Mitchell A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94121 USA. RP Teerlink, JR (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, 111C,Bldg 203,Room 2A-49,4150 Clement St, San Francisco, CA 94121 USA. EM John.Teerlink@ucsf.edu FU Amgen; Corthera; Cytokinetics; Merck; Novartis; Takeda; Trevena FX J.R. Teerlink has received research grants or consulting fees from Amgen, Corthera, Cytokinetics, Merck, Novartis, Takeda, and Trevena. NR 167 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2013 VL 9 IS 3 BP 303 EP + DI 10.1016/j.hfc.2013.04.005 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191NX UT WOS:000322421000007 PM 23809417 ER PT J AU Wang, NC Piccini, JP Fonarow, GC Knight, BP Harinstein, ME Butler, J Lahiri, MK Metra, M Vaduganathan, M Gheorghiade, M AF Wang, Norman C. Piccini, Jonathan P. Fonarow, Gregg C. Knight, Bradley P. Harinstein, Matthew E. Butler, Javed Lahiri, Marc K. Metra, Marco Vaduganathan, Muthiah Gheorghiade, Mihai TI The Potential Role of Nonpharmacologic Electrophysiology-Based Interventions in Improving Outcomes in Patients Hospitalized for Heart Failure SO HEART FAILURE CLINICS LA English DT Article DE Electrophysiology; Heart failure; Hospitalization; Outcomes ID CARDIAC-RESYNCHRONIZATION THERAPY; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; VENTRICULAR SYSTOLIC DYSFUNCTION; AV NODAL ABLATION; ATRIAL-FIBRILLATION; CATHETER ABLATION; RADIOFREQUENCY ABLATION; EJECTION FRACTION; QRS DURATION; PROPHYLACTIC IMPLANTATION AB Hospitalization for heart failure (HHF) is commonly associated with symptomatic improvement in response to standard medical therapy, yet there remains a substantial risk of rehospitalization and death. Clinically stable outpatients and decompensated inpatients represent two types of patients with chronic heart failure. In the former, treatment of common heart rhythm disorders with nonpharmacologic electrophysiology-based interventions is of substantial benefit in select patients. The potential benefits of these interventions in the hospitalized setting are not well studied. In this review, current knowledge is discussed and future research directions are suggested with nonpharmacologic electrophysiology-based interventions to reduce the morbidity and mortality associated with patients with HHF. C1 [Wang, Norman C.; Harinstein, Matthew E.] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA 15213 USA. [Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol, Durham, NC 27705 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA 90095 USA. [Knight, Bradley P.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Butler, Javed] Emory Cardiovasc Clin Res Inst, Dept Med, Div Cardiol, Atlanta, GA 30322 USA. [Lahiri, Marc K.] Henry Ford Hosp, Dept Internal Med, Edith & Benson Ford Heart & Vasc Inst, Detroit, MI 48202 USA. [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, I-25123 Brescia, Italy. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 North Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI Lahiri, Marc/0000-0002-7616-7988; Metra, Marco/0000-0001-6691-8568 FU Boston Scientific; Johnson Johnson; Bard; Biosense Webster; Biotronik; Medtronic; St Jude Medical FX Dr Piccini has received grants for clinical research from Boston Scientific and Johnson & Johnson; is a consultant for Forest Laboratories, Johnson&Johnson, Medtronic, and Sanofi-Aventis. Dr Fonarowis a consultant for Novartis, Medtronic, and Gambro. Dr Knight receives fellowship support from Bard, Biosense Webster, Biotronik, Medtronic, and St Jude Medical; is a speaker for Biosense Webster, Biotronik, Boston Scientific, Medtronic, and St Jude Medical; is a consultant for Biosense Webster, Boston Scientific, and Cameron Health; and is an investigator for Biotronik, Cameron Health, Medtronic, and St Jude Medical. Dr Butler is an investigator for Medtronic, Boston Scientific, and GE Healthcare. Dr Gheorghiade is a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma, CorThera, Cytokinetics Inc, Debio-Pharm, Errekappa Therapeuitici, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, Novartis Pharma, Otsuka Pharmaceuticals, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, and Solvay Pharmaceuticals. All other authors have reported that they have no relationships to disclose relevant to the contents of this article. NR 99 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 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2013 VL 9 IS 3 BP 331 EP + DI 10.1016/j.hfc.2013.04.007 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191NX UT WOS:000322421000009 PM 23809419 ER PT J AU Kuter, DJ AF Kuter, David J. TI The biology of thrombopoietin and thrombopoietin receptor agonists SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Thrombopoietin; Thrombocytopenia; Eltrombopag; Romiplostim; Megakaryocyte ID RECOMBINANT HUMAN THROMBOPOIETIN; HUMAN MEGAKARYOCYTE GROWTH; CHRONIC IMMUNE THROMBOCYTOPENIA; ACUTE MYELOID-LEUKEMIA; MPL-DEFICIENT MICE; PLATELET PRODUCTION; C-MPL; IN-VITRO; DOUBLE-BLIND; HEREDITARY THROMBOCYTHEMIA AB Thrombopoietin (TPO) is the major physiological regulator of platelet production. TPO binds the TPO receptor, activates JAK and STAT pathways, thus stimulating megakaryocyte growth and platelet production. There is no "sensor" of the platelet count; rather TPO is produced in the liver at a constant rate and cleared by TPO receptors on platelets. TPO levels are inversely proportional to the rate of platelet production. Early recombinant TPO molecules were potent stimulators of platelet production and increased platelets in patients with immune thrombocytopenia, chemotherapy-induced thrombocytopenia, myelodysplastic syndromes and platelet apheresis donors. Neutralizing antibodies formed against one recombinant protein and ended their development. A second generation of TPO receptor agonists, romiplostim and eltrombopag, has been developed. Romiplostim is an IgG heavy chain into which four TPO agonist peptides have been inserted. Eltrombopag is an oral small molecule. These activate the TPO receptor by different mechanisms to increase megakaryocyte growth and platelet production. After administration of either to healthy volunteers, there is a delay of 5 days before the platelet count rises and subsequently reaches a peak after 12-14 days. Both have been highly effective in treating ITP and hepatitis C thrombocytopenia. Studies in a wide variety of other thrombocytopenic conditions are underway. C1 [Kuter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Kuter, David J.] Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7858,55 Fruit St, Boston, MA 02114 USA. EM kuter.david@mgh.harvard.edu NR 110 TC 32 Z9 38 U1 0 U2 16 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 JUL PY 2013 VL 98 IS 1 BP 10 EP 23 DI 10.1007/s12185-013-1382-0 PG 14 WC Hematology SC Hematology GA 182UF UT WOS:000321769400006 PM 23821332 ER PT J AU Amparo, F Wang, HB Emami-Naeini, P Karimian, P Dana, R AF Amparo, Francisco Wang, Haobing Emami-Naeini, Parisa Karimian, Parisa Dana, Reza TI The Ocular Redness Index: A Novel Automated Method for Measuring Ocular Injection SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ocular redness; conjunctival injection; ocular surface; ocular symptoms ID RED EYE; BULBAR REDNESS; GRADING SCALES; PRIMARY-CARE; CONJUNCTIVAL REDNESS; MANAGEMENT AB PURPOSE. To develop and validate a novel automated system to assess ocular redness (OR) in clinical images. METHODS. We developed a novel software that quantifies OR in digital images based on a mathematic algorithm using a centesimal continuous scoring scale. Subsequently, we conducted a study to validate the scores obtained with this system by correlating them with those obtained by two physicians using two image-based comparative subjective scales, the Efron and the Validated Bulbar Redness (VBR) grading scales. Additionally, we evaluated the level of clinical agreement between the Ocular Redness Index (ORI) score and the two image-based methods by means of the Bland-Altman analysis. Main outcome measures included correlation and level of agreement between the ORI score, Efron score, and the VBR score. RESULTS. One hundred and two clinical photographs of eyes with OR were evaluated. The ORI scores significantly correlated with the scores obtained by the two clinicians using the Efron (Observer 1, R = 0.925, P < 0.001; Observer 2, R = 0.857, P < 0.001), and VBR (Observer 1, R = 0.830, P < 0.001; Observer 2, R = 0.821, P < 0.001) scales. The Bland-Altman analysis revealed levels of disagreement of up to 30 and 27 units for the ORI-Efron and ORI-VBR score comparisons, respectively. CONCLUSIONS. The ORI provides an objective and continuous scale for evaluating ocular injection in an automated manner, and without need for a trained physician for scoring. The ORI may be used as a new alternative for objective OR evaluation in clinics and in clinical trials. C1 [Amparo, Francisco; Emami-Naeini, Parisa; Karimian, Parisa; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wang, Haobing] Harvard Univ, Sch Med, Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institutes of Health [K24 EY019098] FX Supported by a grant from the National Institutes of Health (Grant K24 EY019098). NR 21 TC 6 Z9 6 U1 3 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2013 VL 54 IS 7 BP 4821 EP 4826 DI 10.1167/iovs.13-12217 PG 6 WC Ophthalmology SC Ophthalmology GA 194MI UT WOS:000322637000052 PM 23766472 ER PT J AU Li, G Kiel, JW Cardenas, DP De La Garza, BH Duong, TQ AF Li, Guang Kiel, Jeffrey W. Cardenas, Damon P. De La Garza, Bryan H. Duong, Timothy Q. TI Postocclusive Reactive Hyperemia Occurs in the Rat Retinal Circulation but Not in the Choroid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE BOLD; MRI; laser speckle imaging; laser Doppler flowmetry; retinal blood flow; choroidal blood flow; reactive hyperemia ID OPTIC-NERVE HEAD; OCULAR BLOOD-FLOW; FUNCTIONAL MRI; INDUCED DILATION; OXYGEN; PRESSURE; FLICKER; VASODILATATION; ARTERIOLES; MECHANISM AB PURPOSE. We tested the hypothesis that retinal blood flow has a postocclusive reactive hyperemia response modulated by occlusion duration and metabolic activity, and that choroidal blood flow does not. METHODS. Anesthetized and paralyzed rats (n = 34) were studied. Retinal and choroidal blood flow was measured by laser speckle imaging and laser Doppler flowmetry, respectively. Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to measure changes in relative blood oxygenation of the retinal and choroidal circulations. Transient carotid occlusion was elicited with a hydraulic occluder on the common carotid artery. Several occlusion durations were tested during dark, constant light, and flicker light conditions to modulate metabolic demand. The hyperemia response magnitude was quantified by integrating the area above the blood flow baseline for the 3 minutes after release of the occlusion. RESULTS. Systemic arterial pressure (108.2 +/- 1.4 mm Hg) was unaffected by the carotid occlusions, and was similar among animals and conditions. Retinal blood flow had a reactive hyperemia, but choroidal blood flow did not (e.g., 14 +/- 2%.sec versus 0.5 +/- 4%.sec after 60-second occlusion). The hyperemia magnitude increased as a nonlinear function of occlusion duration and reached a plateau at occlusion durations <60 second. The hyperemia magnitude was not altered by different lighting conditions at occlusion durations of 15 and 60 seconds. BOLD fMRI results were similar to the laser-based blood flow measurements. CONCLUSIONS. The results indicate that metabolic local control has a negligible role in choroidal blood flow regulation and only partially accounts for the blood flow behavior in the retinal circulation. C1 [Li, Guang; Cardenas, Damon P.; De La Garza, Bryan H.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Li, Guang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Kiel, Jeffrey W.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kiel@uthscsa.edu; duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NIH/NEI [R01 EY014211, EY018855, EY009702]; MERIT Award from the Department of Veterans Affairs; San Antonio Life Science Institute; CTSA [CTSA-8UL1TR000149]; AHA SWA Predoctoral Fellowship [AHA-13PRE14680087] FX Supported in part by the NIH/NEI (R01 EY014211, EY018855, and EY009702), MERIT Award from the Department of Veterans Affairs, and San Antonio Life Science Institute (TQD), and CTSA Pilot Project & Translational Technology (CTSA-8UL1TR000149) and AHA SWA 2012 Predoctoral Fellowship (AHA-13PRE14680087; GL). NR 41 TC 3 Z9 3 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2013 VL 54 IS 7 BP 5123 EP 5131 DI 10.1167/iovs.13-12404 PG 9 WC Ophthalmology SC Ophthalmology GA 194MI UT WOS:000322637000089 PM 23821190 ER PT J AU Wolpin, BM Bao, Y Qian, ZR Wu, C Kraft, P Ogino, S Stampfer, MJ Sato, K Ma, J Buring, JE Sesso, HD Lee, IM Gaziano, JM McTiernan, A Phillips, LS Cochrane, BB Pollak, MN Manson, JE Giovannucci, EL Fuchs, CS AF Wolpin, Brian M. Bao, Ying Qian, Zhi Rong Wu, Chen Kraft, Peter Ogino, Shuji Stampfer, Meir J. Sato, Kaori Ma, Jing Buring, Julie E. Sesso, Howard D. Lee, I-Min Gaziano, John Michael McTiernan, Anne Phillips, Lawrence S. Cochrane, Barbara B. Pollak, Michael N. Manson, JoAnn E. Giovannucci, Edward L. Fuchs, Charles S. TI Hyperglycemia, Insulin Resistance, Impaired Pancreatic -Cell Function, and Risk of Pancreatic Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-MASS INDEX; TYPE-2 DIABETES-MELLITUS; WOMENS HEALTH; INDEPENDENT PREDICTOR; PRIMARY PREVENTION; PHYSICAL-ACTIVITY; FOLLOW-UP; PROINSULIN; GLUCOSE; MEN AB Obesity and diabetes mellitus are associated with an increased risk of pancreatic cancer. These associations may be secondary to consequences of peripheral insulin resistance, pancreatic -cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, and the proinsulin to insulin ratio marks pancreatic -cell dysfunction. This was a prospective, nested case-control study of 449 case patients and 982 control subjects with prediagnostic blood samples and no diabetes history from five prospective US cohorts followed through 2008. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by prediagnostic HbA1c, insulin, proinsulin, and proinsulin to insulin ratio with multivariable-adjusted logistic regression. All P values were two-sided. The highest vs lowest quintiles of HbA1c, insulin, and proinsulin were associated with with an increased risk for pancreatic cancer (odds ratio [OR] 1.79; 95% confidence interval [CI] 1.17 to 2.72, P-trend .04 for HbA1c; OR 1.57; 95% CI 1.08 to 2.30; Ptrend .002 for insulin; and OR 2.22; 95% CI 1.50 to 3.29; P-trend < .001 for proinsulin). Proinsulin to insulin ratio was not associated with pancreatic cancer risk. Results were similar across studies (all P-heterogeneity > .29). In cancers developing 10 or more years after blood collection, the associations with insulin and proinsulin became stronger (highest vs lowest quintile, OR 2.77; 95% CI 1.28 to 5.99 for insulin and OR 3.60; 95% CI 1.68 to 7.72 for proinsulin). In mutually adjusted models including HbA1c, insulin, and proinsulin, only proinsulin remained statistically significant ( highest vs lowest quintile, OR 2.55; 95% CI 1.54 to 4.21; Ptrend < .001). Among participants from five large prospective cohorts, circulating markers of peripheral insulin resistance, rather than hyperglycemia or pancreatic -cell dysfunction, were independently associated with pancreatic cancer risk. C1 [Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wolpin, Brian M.; Bao, Ying; Ogino, Shuji; Stampfer, Meir J.; Ma, Jing; Buring, Julie E.; Sesso, Howard D.; Lee, I-Min; Gaziano, John Michael; Manson, JoAnn E.; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Wolpin, Brian M.; Qian, Zhi Rong; Ogino, Shuji; Sato, Kaori; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bao, Ying; Ogino, Shuji; Stampfer, Meir J.; Ma, Jing; Buring, Julie E.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Wu, Chen; Kraft, Peter; Stampfer, Meir J.; Ma, Jing; Sesso, Howard D.; Lee, I-Min; Manson, JoAnn E.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Buring, Julie E.; Sesso, Howard D.; Lee, I-Min; Gaziano, John Michael; Manson, JoAnn E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Gaziano, John Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Pollak, Michael N.] McGill Univ, Fac Med, Canc Prevent Res Unit, Dept Oncol, Montreal, PQ, Canada. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Phillips, Lawrence S.] Emory Univ, Sch Med, Div Endocrinol & Metab, Atlanta, GA USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org FU National Cancer Institute, National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908]; NIH [CA97193, CA34944, CA40360, HL26490, HL34595, CA047988, HL043851, HL080467]; National Heart, Lung, and Blood Institute, NIH, 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]; NCI [K07 CA140790]; American Society of Clinical Oncology Career Development Award; Howard Hughes Medical Institute Early Career Physician-Scientist Award; Lustgarten Foundation; Promises for Purple FX The NHS and HPFS are supported by the National Cancer Institute, National Institutes of Health (NIH) (grant numbers P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908). The PHS is supported by the NIH (grant numbers CA97193, CA34944, CA40360, HL26490, and HL34595). The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services (contract numbers N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221). The WHS is supported by the NIH (grant numbers CA047988, HL043851, and HL080467). BMW is supported by NCI K07 CA140790, an American Society of Clinical Oncology Career Development Award, a Howard Hughes Medical Institute Early Career Physician-Scientist Award, the Lustgarten Foundation, and Promises for Purple. The study sponsors had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. NR 48 TC 49 Z9 49 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUL PY 2013 VL 105 IS 14 BP 1027 EP 1035 DI 10.1093/jnci/djt123 PG 9 WC Oncology SC Oncology GA 193OK UT WOS:000322569000009 PM 23847240 ER PT J AU Sgroi, DC Carney, E Zarrella, E Steffel, L Binns, SN Finkelstein, DM Szymonifka, J Bhan, AK Shepherd, LE Zhang, Y Schnabel, CA Erlander, MG Ingle, JN Porter, P Muss, HB Pritchard, KI Tu, DS Rimm, DL Goss, PE AF Sgroi, Dennis C. Carney, Erin Zarrella, Elizabeth Steffel, Lauren Binns, Shemeica N. Finkelstein, Dianne M. Szymonifka, Jackie Bhan, Atul K. Shepherd, Lois E. Zhang, Yi Schnabel, Catherine A. Erlander, Mark G. Ingle, James N. Porter, Peggy Muss, Hyman B. Pritchard, Katherine I. Tu, Dongsheng Rimm, David L. Goss, Paul E. TI Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STAGE BREAST-CANCER; 2-GENE EXPRESSION RATIO; ENDOCRINE THERAPY; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; TAMOXIFEN; WOMEN; RECEPTOR; ADHERENCE; SURVIVAL AB Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph nodenegative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole. A prospectiveretrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided. High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] 0.35; 95% confidence interval [CI] 0.16 to 0.75; P .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR 0.33; 95% CI 0.15 to 0.73; P .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P .007). The interaction between H/I and letrozole treatment was statistically significant (P .03). In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence. C1 [Sgroi, Dennis C.; Carney, Erin; Zarrella, Elizabeth; Steffel, Lauren; Binns, Shemeica N.; Bhan, Atul K.] Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Charlestown, MA 02129 USA. [Sgroi, Dennis C.; Carney, Erin; Zarrella, Elizabeth; Steffel, Lauren; Binns, Shemeica N.; Finkelstein, Dianne M.; Szymonifka, Jackie; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc Res, Dept Pathol & Med, Boston, MA 02114 USA. [Shepherd, Lois E.; Pritchard, Katherine I.; Tu, Dongsheng] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. [Zhang, Yi; Schnabel, Catherine A.; Erlander, Mark G.] BioTheranost Inc, San Diego, CA USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Porter, Peggy] Fred Hutchinson Canc Res Ctr, Dept Human Biol, Seattle, WA 98104 USA. [Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. [Pritchard, Katherine I.] Univ Toronto, Dept Med, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, 149 13th St,Rm 6021, Charlestown, MA 02129 USA. EM dsgroi@partners.org FU Avon Foundation; National Institute of Health [R01CA112021]; Breast Cancer Foundation; Department of Defense Breast Cancer Research Program [W81XWH-04-1-0606]; NCI SPORE in breast cancer at Massachusetts General Hospital; Novartis FX This work was supported by grants from the Avon Foundation (to D.C.S. and P.E.G.); the National Institute of Health (R01CA112021 to D.C.S.); the Breast Cancer Foundation (to D.C.S. and P.E.G.); the Department of Defense Breast Cancer Research Program (W81XWH-04-1-0606 to D.C.S.); the NCI SPORE in breast cancer at Massachusetts General Hospital (to P.E.G. and D.C.S.); and Novartis. NR 26 TC 38 Z9 38 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUL PY 2013 VL 105 IS 14 BP 1036 EP 1042 DI 10.1093/jnci/djt146 PG 7 WC Oncology SC Oncology GA 193OK UT WOS:000322569000010 PM 23812955 ER PT J AU Reid, JG Gitlin, MJ Altshuler, LL AF Reid, Jennifer G. Gitlin, Michael J. Altshuler, Lori L. TI Lamotrigine in Psychiatric Disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID TREATMENT-RESISTANT DEPRESSION; BIPOLAR-I-DISORDER; BORDERLINE PERSONALITY-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; LITHIUM MAINTENANCE TREATMENT; CONTROLLED CLINICAL-TRIALS; CONTROLLED 18-MONTH TRIAL; ADD-ON TREATMENT; DOUBLE-BLIND AB Objective: Owing to the prevalence of medication side effects and treatment resistance, prescribers often consider off-label uses of US Food and Drug Administration (FDA)-approved agents for the treatment of persistent symptoms. The authors review the available literature on the FDA-approved and non-FDA-approved uses of lamotrigine in adults with psychiatric disorders. Data Sources: We used PubMed, MEDLINE, and a hand search of relevant literature to find studies published between 1990 and 2012 and available in English language. The following keywords were searched: lamotrigine, psychiatric, mood disorders, depression, personality disorders, anxiety, schizophrenia, side effects, and rash. Study Selection: Data were selected from 29 randomized controlled trials (RCTs). When RCTs were not available, open-label trials (6), retrospective case reviews (10), and case series (4) were summarized. Data Extraction: We extracted results of monotherapy and augmentation trials of lamotrigine on primary and secondary outcome measures. Results: Lamotrigine is generally well tolerated, with the best evidence for the maintenance treatment of bipolar disorder, particularly in prevention of depressive episodes. In acute bipolar depression, meta-analyses suggested a modest benefit, especially for more severely depressed subjects, with switch rates similar to placebo. In unipolar depression, double-blind RCTs noted benefit on subsets of symptoms and improved response in more severely depressed subjects. Data are limited but promising in borderline personality disorder. Use of lamotrigine in schizophrenia and anxiety disorders has little supportive evidence. Conclusions: Lamotrigine is recommended in bipolar maintenance when depression is prominent. It also has a role in treating acute bipolar depression and unipolar depression, though the latter warrants more research. Data are too limited in other psychiatric disorders to recommend its use at this time. (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Reid, Jennifer G.; Gitlin, Michael J.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Angeles Healthcare Syst, West Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA. RP Gitlin, MJ (reprint author), 300 UCLA Med Plaza,Ste 2347, Los Angeles, CA 90095 USA. EM mgitlin@mednet.ucla.edu FU Carl and Roberta Deutsch Foundation; UCLA Mood Disorders Fellowship at the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA FX Funding for this review was provided by the Carl and Roberta Deutsch Foundation, through their support of the UCLA Mood Disorders Fellowship at the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA. NR 62 TC 27 Z9 27 U1 1 U2 19 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2013 VL 74 IS 7 BP 675 EP 684 DI 10.4088/JCP.12r08046 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 193ML UT WOS:000322563800002 PM 23945444 ER PT J AU Hazen, EP McDougle, CJ Volkmar, FR AF Hazen, Eric P. McDougle, Christopher J. Volkmar, Fred R. TI Changes in the Diagnostic Criteria for Autism in DSM-5: Controversies and Concerns SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID SPECTRUM DISORDER; ASPERGERS-DISORDER; CLINICAL-DIAGNOSIS; IV; SPECIFICITY; SENSITIVITY C1 [Hazen, Eric P.; McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Volkmar, Fred R.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. RP Hazen, EP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM ehazen@partners.org NR 16 TC 7 Z9 8 U1 2 U2 39 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2013 VL 74 IS 7 BP 739 EP 740 DI 10.4088/JCP.13ac08550 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 193ML UT WOS:000322563800010 PM 23945452 ER PT J AU Gilman, SE Breslau, J Trinh, NH Fava, M Murphy, JM Smoller, JW AF Gilman, Stephen E. Breslau, Joshua Nhi-Ha Trinh Fava, Maurizio Murphy, Jane M. Smoller, Jordan W. TI Study Data Support the Validity of the Major Depression Bereavement Exclusion Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID NATIONAL EPIDEMIOLOGIC SURVEY; PSYCHOPATHOLOGY; ALCOHOL C1 [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.; Murphy, Jane M.; Smoller, Jordan W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nhi-Ha Trinh; Fava, Maurizio; Murphy, Jane M.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Nhi-Ha Trinh; Fava, Maurizio; Murphy, Jane M.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA. [Breslau, Joshua] RAND Corp, Pittsburgh, PA USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 NR 14 TC 1 Z9 1 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2013 VL 74 IS 7 BP 741 EP 743 DI 10.4088/JCP.12lr08310a PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 193ML UT WOS:000322563800012 PM 23945454 ER PT J AU Wollstein, R Wollstein, A Rodgers, J Ogden, TJ AF Wollstein, Ronit Wollstein, Adi Rodgers, John Ogden, Thomas J. TI A hand therapy protocol for the treatment of lunate overload or early Kienbock's disease SO JOURNAL OF HAND THERAPY LA English DT Article DE Early Kienbock's disease; Therapy protocol; Lunate; Overload ID WRIST; BONE; MORPHOLOGY; ULTRASOUND; NECROSIS; MOTION AB We describe a hand therapy protocol aimed at unloading the wrist and increasing blood supply to the wrist, specifically to the lunate. The protocol was used in a series of patients with clinical radial wrist pain, dysfunction and changes on wrist imaging studies. The patients were not candidates for surgical treatment. Application of the therapy protocol improved objective and subjective parameters such as pain and motion, and may provide a viable treatment option for patients with lunate overload or early Kienbock's disease that are not candidates for surgery. (c) 2013 Hanley & Belfus, an imprint of Elsevier Inc. All rights reserved. C1 [Wollstein, Ronit; Wollstein, Adi] Univ Pittsburgh, Dept Plast Surg, Pittsburgh, PA USA. [Wollstein, Ronit; Wollstein, Adi] Univ Pittsburgh, Dept Orthoped Surg, Pittsburgh, PA USA. [Rodgers, John] UPMC Ctr Rehab Serv, Pittsburgh, PA USA. [Ogden, Thomas J.] VA Pittsburgh Healthcare Syst, Occupat Therapy Serv, Pittsburgh, PA USA. RP Wollstein, R (reprint author), 3550 Terrace St,Scaife Hall,Suite 6B, Pittsburgh, PA 15261 USA. EM wollsteinr@upmc.edu NR 38 TC 3 Z9 3 U1 0 U2 2 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0894-1130 J9 J HAND THER JI J. Hand Ther. PD JUL-SEP PY 2013 VL 26 IS 3 BP 255 EP 260 DI 10.1016/j.jht.2012.12.004 PG 6 WC Orthopedics; Rehabilitation; Surgery SC Orthopedics; Rehabilitation; Surgery GA 192QE UT WOS:000322499500010 PM 23465629 ER PT J AU Wallace, ZS Stone, JH AF Wallace, Zachary S. Stone, John H. TI Treatment of Relapsing Polychondritis with Tocilizumab Reply SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM jhstone@partners.org NR 2 TC 0 Z9 0 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2013 VL 40 IS 7 BP 1232 EP 1233 DI 10.3899/jrheum.130420 PG 2 WC Rheumatology SC Rheumatology GA 185TS UT WOS:000321993800035 PM 23980261 ER PT J AU Chabner, BA Efstathiou, J Dryden-Peterson, S AF Chabner, Bruce A. Efstathiou, Jason Dryden-Peterson, Scott CA Massachusetts Gen Hosp Canc Ctr Univ Botswana Princess Marina Hosp Gaborone Private Hosp Botswana Minist Hlth TI Cancer in Botswana: The Second Wave of AIDS in Sub-Saharan Africa SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Efstathiou, Jason] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Dryden-Peterson, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chabner, BA (reprint author), 10 N Frove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org FU NIAID NIH HHS [K23 AI091434] NR 3 TC 6 Z9 6 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUL PY 2013 VL 18 IS 7 BP 777 EP 778 DI 10.1634/theoncologist.2013-0218 PG 2 WC Oncology SC Oncology GA 192UE UT WOS:000322510100001 PM 23882018 ER PT J AU Fojo, AT Bates, SE Chabner, BA AF Fojo, Antonio Tito Bates, Susan E. Chabner, Bruce A. TI Clinical Trial Results: Sharing Results, Speeding Discoveries SO ONCOLOGIST LA English DT Editorial Material C1 [Fojo, Antonio Tito; Bates, Susan E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fojo, AT (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUL PY 2013 VL 18 IS 7 BP 779 EP 779 PG 1 WC Oncology SC Oncology GA 192UE UT WOS:000322510100002 PM 23882019 ER PT J AU Gainor, JF Shaw, AT AF Gainor, Justin F. Shaw, Alice T. TI Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions SO ONCOLOGIST LA English DT Article DE Non-small cell lung cancer; ROS1; RET; Targeted therapy; Fusion oncogenes ID RECEPTOR TYROSINE KINASE; MEDULLARY-THYROID CARCINOMA; ANAPLASTIC LYMPHOMA KINASE; PHASE-III TRIAL; PROTO-ONCOGENE; NEVER-SMOKERS; GENE FUSIONS; C-ROS; SOMATIC MUTATIONS; KIF5B-RET FUSIONS AB The discovery of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) has stimulated renewed interest in oncogenic fusions as potential therapeutic targets. Recently, genetic alterations in ROS1 and RET were identified in patients with NSCLC. Like ALK, genetic alterations in ROS1 and RET involve chromosomal rearrangements that result in the formation of chimeric fusion kinases capable of oncogenic transformation. Notably, ROS1 and RET rearrangements are rarely found with other genetic alterations, such as EGFR, KRAS, or ALK. This finding suggests that both ROS1 and RET are independent oncogenic drivers that may be viable therapeutic targets. In initial screening studies, ROS1 and RET rearrangements were identified at similar frequencies (approximately 1%-2%), using a variety of genotyping techniques. Importantly, patients with either ROS1 or RET rearrangements appear to have unique clinical and pathologic features that may facilitate identification and enrichment strategies. These features may in turn expedite enrollment in clinical trials evaluating genotype-directed therapies in these rare patient populations. In this review, we summarize the molecular biology, clinical features, detection, and targeting of ROS1 and RET rearrangements in NSCLC. C1 [Gainor, Justin F.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. RP Gainor, JF (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. EM jgainor@partners.org FU U.S. National Institutes of Health [5R01CA164273-02]; V Foundation Translational Research Grant FX This work was supported by a grant from the U.S. National Institutes of Health 5R01CA164273-02 and by a V Foundation Translational Research Grant. NR 97 TC 61 Z9 64 U1 3 U2 22 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUL PY 2013 VL 18 IS 7 BP 865 EP 875 DI 10.1634/theoncologist.2013-0095 PG 11 WC Oncology SC Oncology GA 192UE UT WOS:000322510100015 PM 23814043 ER PT J AU Canellos, GP DeVita, VT AF Canellos, George P. DeVita, Vincent T. TI Emil Frei III: A Personal Remembrance In Memoriam SO ONCOLOGIST LA English DT Biographical-Item C1 [Canellos, George P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [DeVita, Vincent T.] Yale Univ, Yale Canc Ctr, New Haven, CT USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUL PY 2013 VL 18 IS 7 BP 892 EP 893 DI 10.1634/theoncologist.2013-0214 PG 2 WC Oncology SC Oncology GA 192UE UT WOS:000322510100018 ER PT J AU Ahmad, S Rukh, G Varga, TV Ali, A Kurbasic, A Shungin, D Ericson, U Koivula, RW Chu, AY Rose, LM Ganna, A Qi, QB Stancakova, A Sandholt, CH Elks, CE Curhan, G Jensen, MK Tamimi, RM Allin, KH Jorgensen, T Brage, S Langenberg, C Aadahl, M Grarup, N Linneberg, A Pare, G Magnusson, PKE Pedersen, NL Boehnke, M Hamsten, A Mohlke, KL Pasquale, LT Pedersen, O Scott, RA Ridker, PM Ingelsson, E Laakso, M Hansen, T Qi, L Wareham, NJ Chasman, DI Hallmans, G Hu, FB Renstrom, F Orho-Melander, M Franks, PW AF Ahmad, Shafqat Rukh, Gull Varga, Tibor V. Ali, Ashfaq Kurbasic, Azra Shungin, Dmitry Ericson, Ulrika Koivula, Robert W. Chu, Audrey Y. Rose, Lynda M. Ganna, Andrea Qi, Qibin Stancakova, Alena Sandholt, Camilla H. Elks, Cathy E. Curhan, Gary Jensen, Majken K. Tamimi, Rulla M. Allin, Kristine H. Jorgensen, Torben Brage, Soren Langenberg, Claudia Aadahl, Mette Grarup, Niels Linneberg, Allan Pare, Guillaume Magnusson, Patrik K. E. Pedersen, Nancy L. Boehnke, Michael Hamsten, Anders Mohlke, Karen L. Pasquale, Louis T. Pedersen, Oluf Scott, Robert A. Ridker, Paul M. Ingelsson, Erik Laakso, Markku Hansen, Torben Qi, Lu Wareham, Nicholas J. Chasman, Daniel I. Hallmans, Goran Hu, Frank B. Renstrom, Frida Orho-Melander, Marju Franks, Paul W. CA InterAct Consortium DIRECT Consortium TI Gene x Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DIABETES PREVENTION PROGRAM; BODY-MASS INDEX; FTO GENE; ENERGY-INTAKE; VARIANTS; TRAITS; WEIGHT; CHILDREN; ADULTS AB Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal. C1 [Ahmad, Shafqat; Varga, Tibor V.; Ali, Ashfaq; Kurbasic, Azra; Shungin, Dmitry; Koivula, Robert W.; Renstrom, Frida; Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Diabet Ctr, Malmo, Sweden. [Rukh, Gull; Ericson, Ulrika; Orho-Melander, Marju] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden. [Kurbasic, Azra] Steno Diabet Ctr, Diabet Epidemiol Res Grp, DK-2820 Gentofte, Denmark. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Med Sect, Dept Publ Hlth & Clin Med, Umea, Sweden. [Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden. [Chu, Audrey Y.; Rose, Lynda M.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chu, Audrey Y.; Rose, Lynda M.; Curhan, Gary; Tamimi, Rulla M.; Ridker, Paul M.; Qi, Lu; Chasman, Daniel I.; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA. [Ganna, Andrea; Magnusson, Patrik K. E.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Qi, Qibin; Jensen, Majken K.; Qi, Lu; Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Stancakova, Alena; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Sandholt, Camilla H.; Allin, Kristine H.; Grarup, Niels; Pedersen, Oluf; Hansen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Elks, Cathy E.; Brage, Soren; Langenberg, Claudia; Scott, Robert A.; Wareham, Nicholas J.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Curhan, Gary; Tamimi, Rulla M.; Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Curhan, Gary; Tamimi, Rulla M.; Qi, Lu; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Jorgensen, Torben; Aadahl, Mette; Linneberg, Allan] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Pare, Guillaume] McMaster Univ, Genet & Mol Epidemiol Lab, Hamilton, ON, Canada. [Pare, Guillaume] Populat Hlth Res Inst, Hamilton, ON, Canada. [Hallmans, Goran] Umea Univ, Sect Nutr Res, Dept Publ Hlth & Clin Med, Umea, Sweden. [Pedersen, Oluf; Hansen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Hansen, Torben; InterAct Consortium] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Laakso, Markku; DIRECT Consortium] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Hamsten, Anders] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Pasquale, Louis T.] Harvard Univ, Sch Med, Dept Ophthalmol, Mass Eye & Ear Infirm, Boston, MA USA. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Chasman, Daniel I.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Ahmad, S (reprint author), Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Diabet Ctr, Malmo, Sweden. EM paul.franks@med.lu.se RI Grarup, Niels/K-2807-2015; Magnusson, Patrik/C-4458-2017 OI Grarup, Niels/0000-0001-5526-1070; FU Innovative Medicines Initiative [nu115317]; European Union; Novo Nordisk; Swedish Research Council; Pahlssons Foundation; Swedish Heart-Lung Foundation; Skane Regional Health Authority; Wellcome Trust; Medical Research Council [MC_U106179471]; Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care; Novo Nordisk Foundation; European Union [LSHM-CT-2006-037197]; Medical Research Council, UK; Strategic Research grant; Linneus grant; Albert Pahlsson Foundation; Swedish Diabetes Foundation; Knut and Alice Wallenberg Foundation; Academy of Finland; Finnish Diabetes Research Foundation; Finnish Cardiovascular Research Foundation; EVO grant from the Kuopio University Hospital [5263]; NIH [DK093757, DK072193, DK062370]; National Institutes of Health [DK091718, HL071981, HL073168, CA87969, CA49449, CA055075, HL34594, HL088521, U01HG004399, DK080140, 5P30DK46200, U54CA155626, DK58845, U01HG004728-02, EY015473, DK70756, CA134958, DK46200]; Merck Research Laboratories, North Wales, PA; Ministry for Higher Education; GenomEUtwin; US National Institutes of Health; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation [20120197]; Swedish Research Council (VR) [2012-1397]; National Heart, Lung, and Blood Institute [HL043851, HL080467]; National Cancer Institute [CA047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen FX Some of the work leading to this publication benefited from support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nu115317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. The current study was funded by Novo Nordisk, the Swedish Research Council, Pahlssons Foundation, the Swedish Heart-Lung Foundation, and the Skane Regional Health Authority (all to PWF). The Fenland Study is funded by the Wellcome Trust and the Medical Research Council (MC_U106179471). The present part of the HEALTH2006 study was funded by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). The present part of the Inter99 study was funded by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). InterAct study was supported by funding from the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community) and the Medical Research Council, UK. The MDC study was supported by research grants from Swedish Research Council, the Swedish Heart-Lung Foundation, Strategic Research grant to EXODIAB, Linneus grant to Lund University Diabetes Centre (LUDC), The Albert Pahlsson Foundation, The Novo Nordisk Foundation, The Swedish Diabetes Foundation and an equipment grant from The Knut and Alice Wallenberg Foundation. METSIM study: This work has been supported by the Academy of Finland, the Finnish Diabetes Research Foundation, the Finnish Cardiovascular Research Foundation, EVO grant from the Kuopio University Hospital (5263), NIH grants DK093757, DK072193 and DK062370. The NHS study was supported by grants DK091718, HL071981, HL073168, CA87969, CA49449, CA055075, HL34594, HL088521, U01HG004399, DK080140, 5P30DK46200, U54CA155626, DK58845, U01HG004728-02, EY015473, DK70756, CA134958, and DK46200 from the National Institutes of Health, with additional support for genotyping from Merck Research Laboratories, North Wales, PA. The Swedish Twin Registry is supported by the Ministry for Higher Education, the Swedish Research Council, and GenomEUtwin; the US National Institutes of Health; and the Swedish Foundation for Strategic Research. EI and AG were supported by the Swedish Heart-Lung Foundation (grant no. 20120197) and Swedish Research Council (VR; grant no. 2012-1397) when working on this paper. The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 49 Z9 49 U1 0 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2013 VL 9 IS 7 AR e1003607 DI 10.1371/journal.pgen.1003607 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 190EG UT WOS:000322321100013 PM 23935507 ER PT J AU Luo, YX Kaz, AM Kanngurn, S Welsch, P Morris, SM Wang, JP Lutterbaugh, JD Markowitz, SD Grady, WM AF Luo, Yanxin Kaz, Andrew M. Kanngurn, Samornmas Welsch, Piri Morris, Shelli M. Wang, Jianping Lutterbaugh, James D. Markowitz, Sanford D. Grady, William M. TI NTRK3 Is a Potential Tumor Suppressor Gene Commonly Inactivated by Epigenetic Mechanisms in Colorectal Cancer SO PLOS GENETICS LA English DT Article ID SIGNAL-TRANSDUCTION; ESOPHAGEAL ADENOCARCINOMA; BARRETTS-ESOPHAGUS; TRKC; EXPRESSION; DNA; RECEPTORS; GROWTH; CARCINOMA; APOPTOSIS AB NTRK3 is a member of the neurotrophin receptor family and regulates cell survival. It appears to be a dependence receptor, and thus has the potential to act as an oncogene or as a tumor suppressor gene. NTRK3 is a receptor for NT-3 and when bound to NT-3 it induces cell survival, but when NT-3 free, it induces apoptosis. We identified aberrantly methylated NTRK3 in colorectal cancers through a genome-wide screen for hypermethylated genes. This discovery led us to assess whether NTRK3 could be a tumor suppressor gene in the colon. NTRK3 is methylated in 60% of colon adenomas and 67% of colon adenocarcinomas. NTRK3 methylation suppresses NTRK3 expression. Reconstitution of NTRK3 induces apoptosis in colorectal cancers, if NT-3 is absent. Furthermore, the loss of NTRK3 expression associates with neoplastic transformation in vitro and in vivo. We also found that a naturally occurring mutant NTRK3 found in human colorectal cancer inhibits the tumor suppressor activity of NTRK3. In summary, our findings suggest NTRK3 is a conditional tumor suppressor gene that is commonly inactivated in colorectal cancer by both epigenetic and genetic mechanisms whose function in the pathogenesis of colorectal cancer depends on the expression status of its ligand, NT-3. C1 [Luo, Yanxin; Wang, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China. [Luo, Yanxin; Kaz, Andrew M.; Morris, Shelli M.; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kanngurn, Samornmas] Prince Songkla Univ, Fac Med, Tumor Biol Res Unit, Hat Yai, Songkhla, Thailand. [Kanngurn, Samornmas] Prince Songkla Univ, Fac Med, Dept Pathol, Hat Yai, Songkhla, Thailand. [Welsch, Piri] Univ Washington, Sch Med, Div Med Genet, Seattle, WA USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Western Reserve Univ, Sch Med, Ireland Canc Ctr, Cleveland, OH 44106 USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Med Ctr, Cleveland, OH USA. RP Luo, YX (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China. EM wgrady@fhcrc.org FU NIH [RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, P01CA077852]; Burroughs Wellcome Fund Translational Research Award for Clinician Scientist; Programme of Introducing Talents of Discipline to Universities of China [B12003]; International Science & Technology Cooperation Program of China [2011DFA32570]; [5P50CA150964] FX Support for these studies was provided by the NIH (RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, and P01CA077852, WMG), a Burroughs Wellcome Fund Translational Research Award for Clinician Scientist (WMG) (URL: www.bwfund.org), Programme of Introducing Talents of Discipline to Universities of China (B12003, JW) and International Science & Technology Cooperation Program of China (2011DFA32570, JW); and 5P50CA150964 (to SDM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 19 Z9 19 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2013 VL 9 IS 7 AR e1003552 DI 10.1371/journal.pgen.1003552 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 190EG UT WOS:000322321100001 PM 23874207 ER PT J AU Oksenych, V Zhovmer, A Ziani, S Mari, PO Eberova, J Nardo, T Stefanini, M Giglia-Mari, G Egly, JM Coin, F AF Oksenych, Valentyn Zhovmer, Alexander Ziani, Salim Mari, Pierre-Olivier Eberova, Jitka Nardo, Tiziana Stefanini, Miria Giglia-Mari, Giuseppina Egly, Jean-Marc Coin, Frederic TI Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack SO PLOS GENETICS LA English DT Article ID NUCLEOTIDE-EXCISION-REPAIR; TRANSCRIPTION-COUPLED REPAIR; SHORT LIFE-SPAN; DNA-REPAIR; MAMMALIAN-CELLS; CHROMATIN MODIFICATIONS; CANCER PREDISPOSITION; H3K79 METHYLATION; NUCLEOSOME CORE; H3 METHYLATION AB UV-induced DNA damage causes repression of RNA synthesis. Following the removal of DNA lesions, transcription recovery operates through a process that is not understood yet. Here we show that knocking-out of the histone methyltransferase DOT1L in mouse embryonic fibroblasts (MEF DOT1L) leads to a UV hypersensitivity coupled to a deficient recovery of transcription initiation after UV irradiation. However, DOT1L is not implicated in the removal of the UV-induced DNA damage by the nucleotide excision repair pathway. Using FRAP and ChIP experiments we established that DOT1L promotes the formation of the pre-initiation complex on the promoters of UV-repressed genes and the appearance of transcriptionally active chromatin marks. Treatment with Trichostatin A, relaxing chromatin, recovers both transcription initiation and UV-survival. Our data suggest that DOT1L secures an open chromatin structure in order to reactivate RNA Pol II transcription initiation after a genotoxic attack. C1 [Oksenych, Valentyn; Zhovmer, Alexander; Ziani, Salim; Eberova, Jitka; Egly, Jean-Marc; Coin, Frederic] Univ Strasbourg, INSERM, CNRS, IGBMC,Dept Funct Genom & Canc, Strasbourg, France. [Mari, Pierre-Olivier; Giglia-Mari, Giuseppina] Univ Toulouse, UPS, IPBS, Toulouse, France. [Nardo, Tiziana; Stefanini, Miria] CNR, Ist Genet Mol, Pavia, Italy. RP Oksenych, V (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Childrens Hosp,Immune Dis Inst, Boston, MA 02115 USA. EM fredr@igbmc.fr RI Mari, Pierre-Olivier/A-1140-2011; Giglia-Mari, Giuseppina/F-5114-2010; Coin, Frederic/F-5925-2013; OI Giglia-Mari, Giuseppina/0000-0002-9120-6332; Oksenych, Valentyn/0000-0002-5088-3791 FU French National Research Agency (ANR ChromaRep); European Research Council (ERC TransReact) FX Research for this paper was found by the French National Research Agency (ANR ChromaRep) and the European Research Council (ERC TransReact). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 19 Z9 20 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2013 VL 9 IS 7 AR e1003611 DI 10.1371/journal.pgen.1003611 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 190EG UT WOS:000322321100016 PM 23861670 ER PT J AU McLaren, PJ Coulonges, C Ripke, S van den Berg, L Buchbinder, S Carrington, M Cossarizza, A Dalmau, J Deeks, SG Delaneau, O De Luca, A Goedert, JJ Haas, D Herbeck, JT Kathiresan, S Kirk, GD Lambotte, O Luo, M Mallal, S van Manen, D Martinez-Picado, J Meyer, L Miro, JM Mullins, JI Obel, N O'Brien, SJ Pereyra, F Plummer, FA Poli, G Qi, Y Rucart, P Sandhu, MS Shea, PR Schuitemaker, H Theodorou, I Vannberg, F Veldink, J Walker, BD Weintrob, A Winkler, CA Wolinsky, S Telenti, A Goldstein, DB de Bakker, PIW Zagury, JF Fellay, J AF McLaren, Paul J. Coulonges, Cedric Ripke, Stephan van den Berg, Leonard Buchbinder, Susan Carrington, Mary Cossarizza, Andrea Dalmau, Judith Deeks, Steven G. Delaneau, Olivier De Luca, Andrea Goedert, James J. Haas, David Herbeck, Joshua T. Kathiresan, Sekar Kirk, Gregory D. Lambotte, Olivier Luo, Ma Mallal, Simon van Manen, Danielle Martinez-Picado, Javier Meyer, Laurence Miro, Jose M. Mullins, James I. Obel, Niels O'Brien, Stephen J. Pereyra, Florencia Plummer, Francis A. Poli, Guido Qi, Ying Rucart, Pierre Sandhu, Manj S. Shea, Patrick R. Schuitemaker, Hanneke Theodorou, Ioannis Vannberg, Fredrik Veldink, Jan Walker, Bruce D. Weintrob, Amy Winkler, Cheryl A. Wolinsky, Steven Telenti, Amalio Goldstein, David B. de Bakker, Paul I. W. Zagury, Jean-Francois Fellay, Jacques TI Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls SO PLOS PATHOGENS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; AFRICAN-AMERICANS; HOST CONTROL; AIDS; PROGRESSION; ALLELE; POLYMORPHISMS; DETERMINANTS; TRANSMISSION AB Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p=3.6x10(-11)). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5 Delta 32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size. C1 [McLaren, Paul J.; Fellay, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland. [McLaren, Paul J.; Fellay, Jacques] Univ Lausanne, Lausanne, Switzerland. [McLaren, Paul J.; Fellay, Jacques] Univ Hosp Ctr, Inst Microbiol, Lausanne, Switzerland. [McLaren, Paul J.; Ripke, Stephan; Kathiresan, Sekar; de Bakker, Paul I. W.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Coulonges, Cedric; Zagury, Jean-Francois] Chaire Bioinformat Conservatoire Natl Arts & Meti, EA4627, Lab Genom Bioinformat, Paris, France. [Coulonges, Cedric; Meyer, Laurence; Rucart, Pierre; Theodorou, Ioannis; Zagury, Jean-Francois] ANRS Genom Grp, French Agcy Res AIDS & Hepatitis, Paris, France. [Ripke, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [van den Berg, Leonard] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. [Buchbinder, Susan] Bridge HIV, San Francisco Dept Publ Hlth, San Francisco, CA USA. [Carrington, Mary] SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Carrington, Mary; Walker, Bruce D.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Cossarizza, Andrea] Univ Modena, Dept Surg Med Dent & Morphol Sci, I-41100 Modena, Italy. [Cossarizza, Andrea] Reggio Emilia Sch Med, Modena, Italy. [Dalmau, Judith] Univ Autonoma Barcelona, Inst Investigacio Ciencies Salut Germans Trias &, AIDS Res Inst IrsiCaixa, Badalona, Spain. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Delaneau, Olivier] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [De Luca, Andrea] Siena Univ Hosp, Univers Div Infect Dis, Siena, Italy. [De Luca, Andrea] Univ Cattolica Sacro Cuore, Inst Clin Infect Dis, Rome, Italy. [Goedert, James J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Rockville, MD USA. [Haas, David] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Herbeck, Joshua T.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. [Kirk, Gregory D.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Delaneau, Olivier] INSERM U1012, Le Kremlin Bicetre, France. [Lambotte, Olivier] Univ Paris Sud, Le Kremlin Bicetre, France. [Lambotte, Olivier] Hop Bicetre, AP HP, Dept Internal Med & Infect Dis, Le Kremlin Bicetre, France. [Luo, Ma] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Luo, Ma] Natl Microbiol Lab, Winnipeg, MB, Canada. [Mallal, Simon] Murdoch Univ & Pathwest, Inst Immunol & Infect Dis, Perth, WA, Australia. [van Manen, Danielle] Univ Amsterdam, Dept Expt Immunol, Sanquin Res Landsteiner Lab, Amsterdam, Netherlands. [van Manen, Danielle] Univ Amsterdam, Acad Med Ctr, Ctr Infect Dis & Immun Amsterdam, Amsterdam, Netherlands. [Martinez-Picado, Javier] ICREA, Barcelona, Spain. [Meyer, Laurence] Univ Paris Sud, UMRS 1018, Fac Med, INSERM,CESP U1018, Paris, France. [Meyer, Laurence] AP HP, Hopital Bicetre, Epidemiol & Publ Hlth Serv, Le Kremlin Bicetre, France. [Miro, Jose M.] Univ Barcelona, IDIBAPS, Hosp Clin, Infect Dis Serv, Barcelona, Spain. [Obel, Niels] Rigshosp, Natl Univ Hosp, Dept Infect Dis, Copenhagen, Denmark. [O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199034, Russia. [Pereyra, Florencia] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. [Poli, Guido] Univ Vita Salute San Raffaele, Div Immunol Transplantat & Infect Dis, Milan, Italy. [Poli, Guido] Ist Sci San Raffaele, I-20132 Milan, Italy. [Sandhu, Manj S.] Wellcome Trust Sanger Inst, Genet Epidemiol Grp, Hinxton, England. [Sandhu, Manj S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Non Communicable Dis Res Grp, Cambridge, England. [Shea, Patrick R.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC USA. [Theodorou, Ioannis] INSERM, UMRS 945, Paris, France. [Vannberg, Fredrik] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Weintrob, Amy] Univ Hlth Sci, Uniformed Serv, Infect Dis Clin Res Program, Bethesda, MD USA. [Winkler, Cheryl A.] Frederick Natl Lab, SAIC Frederick Inc, NCI,Basic Res Lab, Ctr Canc Res,Mol Genetic Epidemiol Sect, Frederick, MD USA. [Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Div Genet Brigham, Boston, MA USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. RP Fellay, J (reprint author), Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland. EM jacques.fellay@epfl.ch RI de Bakker, Paul/B-8730-2009; SHCS, int. coll. A/G-4083-2011; De Luca, Andrea/G-8810-2011; Fellay, Jacques/A-6681-2009; SHCS, all/G-4072-2011; Martinez-Picado, Javier/G-5507-2012 OI de Bakker, Paul/0000-0001-7735-7858; Wolinsky, Steven/0000-0002-9625-6697; O'Brien, Stephen J./0000-0001-7353-8301; Fellay, Jacques/0000-0002-8240-939X; Cossarizza, Andrea/0000-0002-5381-1558; Shea, Patrick/0000-0001-6804-5131; Martinez-Picado, Javier/0000-0002-4916-2129 FU NIH Office of AIDS Research; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; US NIH National Heart, Lung, and Blood Institute's STAMPEED genomics research program [R01 HL087676]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX Initial funding for the International Collaboration for the Genomics of HIV was provided by the NIH Office of AIDS Research. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The MIGen study was funded by the US NIH National Heart, Lung, and Blood Institute's STAMPEED genomics research program through grant R01 HL087676. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. A full statement of funding for the contributing cohorts is listed in the supplementary materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 35 Z9 36 U1 2 U2 23 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2013 VL 9 IS 7 AR e1003515 DI 10.1371/journal.ppat.1003515 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 190CX UT WOS:000322316700050 PM 23935489 ER PT J AU Meis, LA Schaaf, KW Erbes, CR Polusny, MA Miron, LR Schmitz, TM Nugent, SM AF Meis, Laura A. Schaaf, Kathryn Wilder Erbes, Christopher R. Polusny, Melissa A. Miron, Lynsey R. Schmitz, Theresa M. Nugent, Sean M. TI Interest in Partner-Involved Services Among Veterans Seeking Mental Health Care From a VA PTSD Clinic SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD; couples; veterans; treatment preferences ID POSTTRAUMATIC-STRESS-DISORDER; TREATMENT PREFERENCES; FAMILY; ADJUSTMENT; SYMPTOMS; COUPLES; INTERVENTION; SATISFACTION; PREDICTORS; ENGAGEMENT AB Associations between PTSD and difficulties in intimate relationships have prompted national calls for partner-involvement in treatment for PTSD. However, research is limited evaluating patient preferences for the format of these services or predictors of these preferences. Such information is vital to shaping services so they are relevant to those most interested in them and to those with greatest need. To address these gaps, we surveyed 185 coupled veterans as they presented for mental health appointments at a VA PTSD treatment clinic. We assessed broad interest in greater partner-involvement, specific interest in couple therapy, and potential predictors of these interests, including family concerns, relationship satisfaction, PTSD symptom severity, and combat era. We found unique positive associations between interest in partner-involvement and both family concerns and relationship satisfaction, suggesting those most interested in partner-involvement are likely those experiencing the greatest family concerns and the most satisfied in their intimate relationships. Associations between interest and PTSD severity were nonsignificant. Interest in couple therapy was significantly greater among returning veterans than Vietnam/Korean War Veterans. However, these two groups did not vary significantly in their interest in greater partner-involvement more broadly. Discussion of findings considers the roles of both insight into PTSD-related family problems and relationship satisfaction in motivating interest in partner-involvement in care, the potential need to address motivation for partner-involvement among veterans in distressed relationships, and the importance of alternative methods of partner-involvement to full courses of couple therapy, particularly for Vietnam/Korean War era veterans. C1 [Meis, Laura A.; Polusny, Melissa A.; Nugent, Sean M.] Minneapolis Vet Affairs Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Meis, Laura A.; Nugent, Sean M.] Univ Minnesota, Dept Med, Sch Med, Minneapolis, MN 55455 USA. [Schaaf, Kathryn Wilder; Erbes, Christopher R.; Miron, Lynsey R.] Minneapolis Vet Affairs Hlth Care Syst, Minneapolis, MN 55417 USA. [Schaaf, Kathryn Wilder] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Erbes, Christopher R.; Polusny, Melissa A.] Univ Minnesota, Dept Psychiat, Sch Med, Minneapolis, MN 55455 USA. [Schmitz, Theresa M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Schmitz, Theresa M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Meis, LA (reprint author), Minneapolis Vet Affairs Hlth Care Syst, Ctr Chron Dis Outcomes Res, 1 Vet Dr 152, Minneapolis, MN 55417 USA. EM laura.meis@va.gov NR 39 TC 7 Z9 7 U1 2 U2 12 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JUL PY 2013 VL 5 IS 4 BP 334 EP 342 DI 10.1037/a0028366 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 189RT UT WOS:000322286700005 ER PT J AU Chang, G Pomahac, B AF Chang, Grace Pomahac, Bohdan TI Psychosocial Changes 6 Months after Face Transplantation SO PSYCHOSOMATICS LA English DT Article ID OUTCOMES; FUTURE AB Background: The goal of facial transplantation is to transform severely deformed features in a single, complex operation. Although nearly 20 have been completed since 2005, there is limited information about the subsequent psychosocial status of recipients. Objective: The purpose of this study is to describe such changes as captured on a variety of psychosocial measures 3 and 6 months after full facial transplantation among 3 adults who all completed a comprehensive psychiatric assessment before the procedure. Results: We hypothesized and found that participants experienced significant improvement on quality of life measures of physical and mental health based on the MOS-SF -12. While the recipients experienced a decline in their physical quality of life in the 3 months immediately after surgery, they had improvement by 6 months (p = 0.02). Overall mental health showed steady improvement from the time before surgery to 6 months later (p = 0.04). These changes, however, were not reflected in another popular measure of quality of life, the EQ-5D. There were no changes in participants ' self-esteem or dyadic function over the same period of time. Conclusion: As facial transplantation evolves from being a novel surgical procedure to an increasingly common clinical practice, future efforts to delineate the psychosocial changes experienced by recipients might include mixed methods analyses, with both qualitative and quantitative data, as well as collaborative assessment protocols shared among facial transplantation programs. C1 [Chang, Grace; Pomahac, Bohdan] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chang, Grace; Pomahac, Bohdan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chang, Grace] VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP Chang, G (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM grace.chang2@va.gov FU Department of Defense [W911QY-09-C-0216]; Brigham and Women's Hospital under the Biomedical Translational Initiative [W911QY-09-C-0216]; [K24 AA000289] FX This research was supported by contract (W911QY-09-C-0216) between the Department of Defense and the Brigham and Women's Hospital under the Biomedical Translational Initiative and K24 AA000289 to Grace Chang. NR 19 TC 11 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2013 VL 54 IS 4 BP 367 EP 371 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 191LX UT WOS:000322415600008 PM 23194929 ER PT J AU Restrepo, MI Peterson, J Fernandez, JF Qin, ZH Fisher, AC Nicholson, SC AF Restrepo, Marcos I. Peterson, Janet Fernandez, Juan F. Qin, Zhihai Fisher, Alan C. Nicholson, Susan C. TI Comparison of the Bacterial Etiology of Early-Onset and Late-Onset Ventilator-Associated Pneumonia in Subjects Enrolled in 2 Large Clinical Studies SO RESPIRATORY CARE LA English DT Article DE ventilator-associated pneumonia; ICU; outcome and process assessment; critical care; microbiology; early onset; late onset; mechanical ventilation ID INADEQUATE ANTIMICROBIAL TREATMENT; INTENSIVE-CARE-UNIT; LARGE US DATABASE; NOSOCOMIAL PNEUMONIA; EPIDEMIOLOGY; OUTCOMES; SAFETY; MULTICENTER; INFECTIONS; MORTALITY AB BACKGROUND: Ventilator-associated pneumonia (YAP) is classified as early-onset or late-onset, in part, to identify subjects at risk for infection with resistant pathogens. We assessed differences in the bacterial etiology of early-onset versus late-onset YAP. METHODS: Subjects enrolled in 2004-2006 in 2 clinical studies of doripenem versus imipenem or piperacillin/tazobactam, with a diagnosis of VAP (n = 500) were included in the analysis. Subjects were classified by ventilator status: early-onset YAP (< 5 d of ventilation) or late-onset VAP (>= 5 d of ventilation). Baseline demographics and bacterial etiology were analyzed by YAP status. RESULTS: Late-onset YAP subjects had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores (mean 16.6 versus 15.5, P = .008). There were no significant differences in Clinical Pulmonary Infection Score, sex, age, or presence of bacteremia between the groups. A total of 496 subjects had a baseline pathogen, and 50% of subjects in each group had >= 2 pathogens. With the exception of Staphylococcus aureus, which was common in early-onset YAP, the pathogens (including potentially multidrug-resistant (MDR) pathogens) isolated from early-onset versus late-onset YAP were not significantly different between groups. Acinetobacter baumannii or Pseudomonas aeruginosa with decreased susceptibility to any study drug was observed in early-onset and late-onset YAP subjects. CONCLUSIONS: There were no significant differences in the prevalence of potential MDR pathogens associated with early-onset or late-onset YAP, even in subjects with prior antibiotics. Empiric therapy for early-onset YAP should also include agents likely to be effective for potential MDR pathogens. Further prospective studies should evaluate microbiology trends in subjects with YAP. C1 [Restrepo, Marcos I.; Fernandez, Juan F.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care, San Antonio, TX 78229 USA. [Peterson, Janet; Qin, Zhihai; Fisher, Alan C.; Nicholson, Susan C.] Johnson & Johnson Pharmaceut, Janssen Sci Affairs, Raritan, NJ USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, Audie Murphy Div L, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, 11C6,ALMD 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [K23HL096054] FX Dr Restrepo was partly supported by grant K23HL096054 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Department of Veterans Affairs; nor the University of Texas Health Science Center at San Antonio. NR 24 TC 26 Z9 26 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD JUL PY 2013 VL 58 IS 7 BP 1220 EP 1225 DI 10.4187/respcare.02173 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 185BF UT WOS:000321939500013 PM 23307825 ER PT J AU Cherry, ABC Gagne, KE Mcloughlin, EM Baccei, A Gorman, B Hartung, O Miller, JD Zhang, J Zon, RL Ince, TA Neufeld, EJ Lerou, PH Fleming, MD Daley, GQ Agarwal, S AF Cherry, Anne B. C. Gagne, Katelyn E. Mcloughlin, Erin M. Baccei, Anna Gorman, Bryan Hartung, Odelya Miller, Justine D. Zhang, Jin Zon, Rebecca L. Ince, Tan A. Neufeld, Ellis J. Lerou, Paul H. Fleming, Mark D. Daley, George Q. Agarwal, Suneet TI Induced Pluripotent Stem Cells with a Mitochondrial DNA Deletion SO STEM CELLS LA English DT Article DE Induced pluripotent stem cells; Pearson's marrow pancreas syndrome; Mitochondrial DNA; Heteroplasmy; Human genetics; Hematopoiesis ID HEREDITARY OPTIC NEUROPATHY; MARROW-PANCREAS-SYNDROME; HUMAN SOMATIC-CELLS; SKELETAL-MUSCLE; DEFINED FACTORS; MUTATION; MTDNA; FIBROBLASTS; DYSFUNCTION; GENERATION AB In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here, we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases. STEM CELLS2013;31:1287-1297 C1 [Cherry, Anne B. C.; Gagne, Katelyn E.; Mcloughlin, Erin M.; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Neufeld, Ellis J.; Daley, George Q.; Agarwal, Suneet] Boston Childrens Hosp, Stem Cell Transplantat Program, Div Hematol Oncol, Boston, MA USA. [Cherry, Anne B. C.; Gagne, Katelyn E.; Mcloughlin, Erin M.; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Daley, George Q.; Agarwal, Suneet] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Cherry, Anne B. C.; Gagne, Katelyn E.; Mcloughlin, Erin M.; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Daley, George Q.; Agarwal, Suneet] Harvard Stem Cell Inst, Cambridge, MA USA. [Cherry, Anne B. C.; Gagne, Katelyn E.; Mcloughlin, Erin M.; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Daley, George Q.; Agarwal, Suneet] Manton Ctr Orphan Dis Res, Boston, MA USA. [Cherry, Anne B. C.; Mcloughlin, Erin M.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Cherry, Anne B. C.; Mcloughlin, Erin M.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Baccei, Anna; Gorman, Bryan; Lerou, Paul H.] Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. [Baccei, Anna; Gorman, Bryan; Lerou, Paul H.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Baccei, Anna; Gorman, Bryan; Lerou, Paul H.] Boston Childrens Hosp, Dept Newborn Med, Boston, MA USA. [Baccei, Anna; Gorman, Bryan; Lerou, Paul H.] Harvard Univ, Sch Med, Boston, MA USA. [Ince, Tan A.] Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Dept Pathol, Miami, FL 33136 USA. [Ince, Tan A.] Univ Miami, Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA. [Fleming, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. RP Agarwal, S (reprint author), 3 Blackfan Circle,CLS 3002, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; suneet.agarwal@childrens.harvard.edu FU National Heart, Lung, and Blood Institute [U01 HL100001]; Progenitor Cell Biology Consortium; Manton Center for Orphan Disease Research; [K08 HL089150] FX We thank the patients and families for their participation in research. The work was supported by grants from the National Heart, Lung, and Blood Institute: U01 HL100001, Progenitor Cell Biology Consortium (G. Q. D.) and K08 HL089150 (S. A.), and the Manton Center for Orphan Disease Research (G. Q. D. and S.A.). NR 33 TC 37 Z9 38 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 2013 VL 31 IS 7 BP 1287 EP 1297 DI 10.1002/stem.1354 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 176XB UT WOS:000321339000008 PM 23400930 ER PT J AU Admon, R Milad, MR Hendler, T AF Admon, Roee Milad, Mohammed R. Hendler, Telma TI A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities SO TRENDS IN COGNITIVE SCIENCES LA English DT Review DE stress; neuroimaging; fear extinction; risk factor; amygdala; functional connectivity; PTSD; prefrontal cortex; hippocampus ID SEROTONIN TRANSPORTER GENOTYPE; VENTROMEDIAL PREFRONTAL CORTEX; CATECHOL-O-METHYLTRANSFERASE; ACUTELY TRAUMATIZED SAMPLE; FEAR EXTINCTION; HIPPOCAMPAL VOLUME; ANXIETY DISORDERS; 5-HTTLPR POLYMORPHISM; NUCLEUS-ACCUMBENS; GENE POLYMORPHISM AB Discriminating neural abnormalities into the causes versus consequences of psychopathology would enhance the translation of neuroimaging findings into clinical practice. By regarding the traumatic encounter as a reference point for disease onset, neuroimaging studies of post-traumatic stress disorder (PTSD) can potentially allocate PTSD neural abnormalities to either predisposing (pre-exposure) or acquired (post-exposure) factors. Based on novel research strategies in PTSD neuroimaging, including genetic, environmental, twin, and prospective studies, we provide a causal model that accounts for neural abnormalities in PTSD, and outline its clinical implications. Current data suggest that abnormalities within the amygdala and dorsal anterior cingulate cortex represent predisposing risk factors for developing PTSD, whereas dysfunctional hippocampal ventromedial prefrontal cortex (vmPFC) interactions may become evident only after having developed the disorder. C1 [Admon, Roee] Harvard Univ, McLean Hosp, Sch Med, Ctr Depress Anxiety & Stress Res, Boston, MA 02114 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hendler, Telma] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Wohl Inst Adv Imaging, Funct Brain Ctr, IL-69978 Tel Aviv, Israel. [Hendler, Telma] Tel Aviv Univ, Sackler Fac Med, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Hendler, Telma] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. RP Admon, R (reprint author), Harvard Univ, McLean Hosp, Sch Med, Ctr Depress Anxiety & Stress Res, Boston, MA 02114 USA. EM radmon@mclean.harvard.edu; talma@tasmc.health.gov.il FU U.S. Department of Defense (DoD) [W81XWH-11-2-0008]; Israel-Centers of Excellence (I-CORE) Program of the Planning and Budgeting Committee; Israel Science Foundation [51/11]; Adams Super Center for Brain Studies, Tel Aviv University FX This work was supported by a grant from the U.S. Department of Defense (DoD) award number W81XWH-11-2-0008; Israel-Centers of Excellence (I-CORE) Program of the Planning and Budgeting Committee, and the Israel Science Foundation (grant no. 51/11); and Adams Super Center for Brain Studies, Tel Aviv University. We would like to thank: Dr David Papo for his fruitful comments on earlier versions; Dr Gadi Lubin and Dr Eyal Fructer from the Israel Defense Forces medical corps for their support of this work; and Mr Matan Shalita for graphical assistance. NR 108 TC 57 Z9 57 U1 8 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JUL PY 2013 VL 17 IS 7 BP 337 EP 347 DI 10.1016/j.tics.2013.05.005 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 191NJ UT WOS:000322419500009 PM 23768722 ER PT J AU Squadrito, ML Etzrodt, M De Palma, M Pittet, MJ AF Squadrito, Mario Leonardo Etzrodt, Martin De Palma, Michele Pittet, Mikael J. TI MicroRNA-mediated control of macrophages and its implications for cancer SO TRENDS IN IMMUNOLOGY LA English DT Review DE miRNA; inflammation; monocyte; tumor-associated macrophage; cancer ID TUMOR-ASSOCIATED MACROPHAGES; NF-KAPPA-B; DENDRITIC CELLS; IN-VIVO; INFLAMMATORY RESPONSES; ALTERNATIVE ACTIVATION; FUNCTIONAL MICRORNAS; OVARIAN-CANCER; BREAST-CANCER; POLARIZATION AB Deregulation of microRNAs (miRNAs) can drive oncogenesis, tumor progression, and metastasis by acting cell-autonomously in cancer cells. However, solid tumors are also infiltrated by large amounts of non-neoplastic stromal cells, including macrophages, which express several active miRNAs. Tumor-associated macrophages (TAMs) enhance angiogenic, immunosuppressive, invasive, and metastatic programming of neoplastic tissue and reduce host survival. Here, we review the role of miRNAs (including miR-155, miR-146, and miR-511) in the control of macrophage production and activation, and examine whether reprogramming miRNA activity in TAMs and/or their precursors might be effective for controlling tumor progression. C1 [Squadrito, Mario Leonardo; De Palma, Michele] Swiss Fed Inst Technol, EPFL, Sch Life Sci, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland. [Etzrodt, Martin; Pittet, Mikael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP De Palma, M (reprint author), Swiss Fed Inst Technol, EPFL, Sch Life Sci, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland. EM michele.depalma@epfl.ch; mpittet@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015; De Palma, Michele/L-5350-2016 OI Etzrodt, Martin/0000-0003-1928-3904; FU European Research Council (ERC); National Centres of Competence in Research (Oncology Program); Fonds National Suisse de la Recherche Scientifique (SNSF); Anna Fuller fund; US National Institutes of Health (NIH) [R01-AI084880, P50-CA086355, U54-CA126515] FX We apologize to the authors whose work we could not cite because of the limit on the number of references. This work was supported in part by the European Research Council (ERC), the National Centres of Competence in Research (Oncology Program), Fonds National Suisse de la Recherche Scientifique (SNSF), and Anna Fuller fund (to M.D.P), and by US National Institutes of Health (NIH) grants R01-AI084880, P50-CA086355 and U54-CA126515 (to M.J.P.). NR 100 TC 49 Z9 54 U1 3 U2 37 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JUL PY 2013 VL 34 IS 7 BP 350 EP 359 DI 10.1016/j.it.2013.02.003 PG 10 WC Immunology SC Immunology GA 185SB UT WOS:000321989500006 PM 23498847 ER PT J AU Brennan, CW Daly, BJ Jones, KR AF Brennan, Caitlin W. Daly, Barbara J. Jones, Katherine R. TI State of the Science: The Relationship Between Nurse Staffing and Patient Outcomes SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article DE nurse staffing; patient outcomes; systems approach; nurses' practices patterns; delivery of health care ID HEART-FAILURE-OUTCOMES; LENGTH-OF-STAY; HEALTH-CARE; SKILL MIX; QUALITY; MORTALITY; IMPACT; MODEL; INFORMATICS; ENVIRONMENT AB Over a decade of research on the relationship between nurse staffing and patient outcomes has demonstrated the important role of nurses in the provision of high-quality, safe care, yet currently, no evidence-based nurse staffing guidelines exist. A systematic review of reviews was conducted to explore reasons why this is the case and recommend directions for future research to improve upon this gap. Authors of the 29 included reviews reported variability in methods and measurement approaches, lack of incorporation of nurse processes and system factors that potentially affect relationships among variables, and overall inconsistencies in results across primary studies. We propose use of an Integrated Framework for a Systems Approach to Nurse Staffing Research to inform the development of applicable conceptual models. Future studies that use a systems approach and focus on establishing causal relationships among variables will potentially strengthen the evidence and advance the science in this area. C1 [Brennan, Caitlin W.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Brennan, Caitlin W.; Daly, Barbara J.; Jones, Katherine R.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Brennan, Caitlin W.] Louis Stokes Cleveland VA Med Ctr, Vet Affairs Natl Qual Scholars Program, Cleveland, OH USA. RP Brennan, CW (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 South Huntington Ave 152M, Boston, MA 02130 USA. EM cww2@case.edu FU NIH [T32]; Health Resources and Services Administration Faculty Loan Repayment Program; Frances Payne Bolton School of Nursing Alumni Association research award; Sigma Theta Tau International Alpha Mu Chapter research award FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The first author received the following funding/financial support to conduct this work: The NIH T32 Multiple Morbidities in Vulnerable Populations: Nurse Scientist Training Predoctoral Fellowship, The Health Resources and Services Administration Faculty Loan Repayment Program, a Frances Payne Bolton School of Nursing Alumni Association research award, and a Sigma Theta Tau International Alpha Mu Chapter research award. NR 81 TC 14 Z9 15 U1 7 U2 27 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD JUL PY 2013 VL 35 IS 6 BP 760 EP 794 DI 10.1177/0193945913476577 PG 35 WC Nursing SC Nursing GA 191FH UT WOS:000322397900006 PM 23444060 ER PT J AU Wenger, A Wirth, W Hudelmaier, M Noebauer-Huhmann, I Trattnig, S Bloecker, K Frobell, RB Kwoh, CK Eckstein, F Englund, M AF Wenger, Andrea Wirth, Wolfgang Hudelmaier, Martin Noebauer-Huhmann, Iris Trattnig, Siegfried Bloecker, Katja Frobell, Richard B. Kwoh, C. Kent Eckstein, Felix Englund, Martin TI Meniscus Body Position, Size, and Shape in Persons With and Persons Without Radiographic Knee Osteoarthritis: Quantitative Analyses of Knee Magnetic Resonance Images From the Osteoarthritis Initiative SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ARTICULAR-CARTILAGE; ELDERLY PERSONS; FOLLOW-UP; JOINT; MRI; PATHOLOGY; LESIONS; TEARS; ASSOCIATION; SURGERY AB ObjectiveTo quantitatively evaluate the position, size, and shape of the menisci in subjects with radiographic knee osteoarthritis (OA) compared to subjects without OA, using magnetic resonance imaging (MRI). MethodsWe studied the right knees of 39 Osteoarthritis Initiative participants (24 women and 15 men with a mean age of 59.6 +/- 8.7 years) with medial compartment radiographic tibiofemoral OA (Kellgren/Lawrence grade of 2 or 3). Subjects were matched individually for age, sex, and height to controls without knee OA and without risk factors for knee OA. The right knees of the controls were used as references. One observer performed manual segmentation of the tibial plateau and the medial and lateral meniscus based on a coronally reconstructed double-echo steady-state sequence with water excitation, focusing on 5 central 3T MRIs. ResultsIn OA knees, there was less meniscal coverage of the medial tibial plateau (435 mm(2) versus 515 mm(2); P = 0.0004), the medial meniscus body showed more extrusion (2.64 mm versus 0.53 mm; P < 0.0001), and the peripheral margin had a more convex shape, i.e., bulged more (mean 0.61 mm versus 0.27 mm; P < 0.0001). The thickness or volume of the medial meniscus body of OA knees did not differ substantially from reference knees. In contrast, in OA knees the lateral meniscus body had a larger volume (mean 266 mm(3) versus 224 mm(3); P = 0.0005) and extruded more (mean 1.16 mm versus -1.01 mm; P < 0.0001), and the external margin bulged more (mean 0.53 mm versus 0.35 mm; P < 0.0001), than in reference knees. ConclusionOur findings indicate altered meniscal position and shape (i.e., more bulging) in both compartments in medial compartment knee OA. These changes may be important features of OA pathogenesis and/or disease consequences. C1 [Wenger, Andrea; Wirth, Wolfgang; Hudelmaier, Martin; Bloecker, Katja; Frobell, Richard B.; Eckstein, Felix] Paracelsus Med Univ, A-5020 Salzburg, Austria. [Wirth, Wolfgang; Hudelmaier, Martin] Chondrometrics GmbH, Ainring, Germany. [Noebauer-Huhmann, Iris; Trattnig, Siegfried] Med Univ Vienna, Vienna, Austria. [Frobell, Richard B.; Englund, Martin] Lund Univ, Lund, Sweden. [Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Englund, Martin] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Wenger, A (reprint author), Paracelsus Med Univ, Inst Anat & Musculoskeletal Res, Strubergasse 21, A-5020 Salzburg, Austria. EM andrea.wenger@pmu.ac.at RI Wirth, Wolfgang/C-8724-2011; OI Wirth, Wolfgang/0000-0002-2297-8283; Englund, Martin/0000-0003-3320-2437 FU Swedish Research Council; Kock Foundation; King Gustaf V's 80-Year Foundation; Lund University Faculty of Medicine; Royal Physiographic Society in Lund; Osteoarthritis Initiative (OAI); NIH [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, N01-AR-2-2262]; Pfizer Inc.; Novartis Pharmaceuticals Corporation; Merck Research Laboratories; GlaxoSmithKline; Paracelsus Medical University Research Fund [R-10-05-021-HUD]; Merck Serono; Perceptive Imaging; Pfizer; Abbott; BioClinica; Medtronic; Sanofi; Novartis FX Dr. Englund's work was supported by the Swedish Research Council, the Kock Foundation, King Gustaf V's 80-Year Foundation, the Lund University Faculty of Medicine, and the Royal Physiographic Society in Lund. The study and image acquisition were supported by the Osteoarthritis Initiative (OAI). The OAI is a public-private partnership comprising 5 NIH contracts (N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, and N01-AR-2-2262) and conducted by the OAI Study Investigators. Private funding partners include Pfizer Inc., Novartis Pharmaceuticals Corporation, Merck Research Laboratories, and GlaxoSmithKline. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This article has received the approval of the OAI Publications Committee based on a review of its scientific content and data interpretation. The image analysis was supported by the Paracelsus Medical University Research Fund (grant R-10-05-021-HUD).; Dr. Wirth has received consulting fees from Merck Serono (less than $10,000) and is co-owner of Chondrometrics GmbH. Dr. Hudelmaier has received consulting fees from Perceptive Imaging (less than $10,000) and has a part-time appointment with Chondrometrics GmbH. Dr. Kwoh has received consulting fees, speaking fees, and/or honoraria from Pfizer (less than $10,000). Dr. Eckstein has received consulting fees, speaking fees, and/or honoraria from Abbott, BioClinica, Perceptive Imaging, and Medtronic (less than $10,000 each) and from Merck Serono, Sanofi, and Novartis (more than $10,000 each), and he is co-owner and chief executive officer of Chondrometrics GmbH. NR 42 TC 22 Z9 22 U1 1 U2 13 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 JUL PY 2013 VL 65 IS 7 BP 1804 EP 1811 DI 10.1002/art.37947 PG 8 WC Rheumatology SC Rheumatology GA 187XM UT WOS:000322155000016 PM 23529645 ER PT J AU Davis, TE Kis-Toth, K Szanto, A Tsokos, GC AF Davis, Trevor E. Kis-Toth, Katalin Szanto, Attila Tsokos, George C. TI Glucocorticoids Suppress T Cell Function by Up-Regulating MicroRNA-98 SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION; KINASE PHOSPHATASE-1; MULTIPLE-SCLEROSIS; APOPTOSIS; PROTEIN; INFLAMMATION; DEXAMETHASONE; ACTIVATION; MECHANISMS AB ObjectiveTo identify microRNAs (miRNAs) in human T cells that can explain known antiinflammatory properties of steroids. MethodsActivated human CD4+ T cells from healthy donors were exposed to 1 M methylprednisolone (MP) in vitro and then subjected to miRNA and messenger RNA microarray analyses. Changes in expression profiles were recorded. Using quantitative polymerase chain reaction (qPCR), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we confirmed the suppression of predicted targets, and through miRNA transfection experiments, we could suggest mechanistic links. ResultsWe identified numerous steroid-responsive genes and miRNAsmany known and some novelincluding multiple previously unknown proinflammatory genes suppressed by MP. Further studies using qPCR, flow cytometry, and ELISA demonstrated that methylprednisolone increased the expression of miRNA-98 (miR-98) and suppressed the levels of predicted targets, including interleukin-13 and 3 tumor necrosis factor receptors (TNFRs): Fas, FasL, and TNFR superfamily member 1B. Forced expression of miR-98 in T cells resulted in suppression of the same targets. ConclusionThe findings of this study demonstrate a link between miR-98 expression and the effects of MP and provide evidence suggesting that MP acts through miR-98 to inhibit specific proinflammatory targets. Identification of this antiinflammatory mechanism of glucocorticoids is important, since it may pave the way toward the elusive goal of dissociating adverse effects from therapeutic effects. C1 [Davis, Trevor E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Davis, Trevor E.] Tufts Med Ctr, Floating Hosp Children, Boston, MA 02111 USA. [Kis-Toth, Katalin; Tsokos, George C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kis-Toth, Katalin; Szanto, Attila; Tsokos, George C.] Harvard Univ, Sch Med, Boston, MA USA. [Szanto, Attila] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Davis, TE (reprint author), Tufts Med Ctr, Floating Hosp Children, Div Pediat Rheumatol, 800 Washington St, Boston, MA 02111 USA. EM tdavis2@tuftsmedicalcenter.org; gtsokos@bidmc.harvard.edu FU NIH [5T32-AI-074549-04, R01-AI-4229]; Harvard Catalyst, the Harvard Clinical and Translational Science Center; NIH [National Center for Research Resources and the National Center for Advancing Translational Sciences] [8UL1-TR-000170-05]; Harvard University; GlaxoSmithKline; Eli Lilly; Biogen Idec FX Supported by the NIH (grants 5T32-AI-074549-04 and R01-AI-4229 to Dr. Tsokos) and by Harvard Catalyst, the Harvard Clinical and Translational Science Center (funded in part by the NIH [National Center for Research Resources and the National Center for Advancing Translational Sciences award 8UL1-TR-000170-05] and by financial contributions from Harvard University and its affiliated academic health care centers).; Dr. Tsokos has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline, Eli Lilly, and Biogen Idec (less than $10,000 each). NR 50 TC 14 Z9 16 U1 0 U2 4 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 JUL PY 2013 VL 65 IS 7 BP 1882 EP 1890 DI 10.1002/art.37966 PG 9 WC Rheumatology SC Rheumatology GA 187XM UT WOS:000322155000024 PM 23575983 ER PT J AU Mosenzon, O Raz, I Scirica, BM Hirshberg, B Stahre, CI Steg, PG Davidson, J Ohman, P Price, DL Frederich, B Udell, JA Braunwald, E Bhatt, DL AF Mosenzon, O. Raz, I. Scirica, B. M. Hirshberg, B. Stahre, C. I. Steg, P. G. Davidson, J. Ohman, P. Price, D. L. Frederich, B. Udell, J. A. Braunwald, E. Bhatt, D. L. TI Baseline characteristics of the patient population in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR)-TIMI 53 trial SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE trial patient; baseline characteristics; diabetes mellitus ID GLUCAGON-LIKE PEPTIDE-1; ISCHEMIA-REPERFUSION INJURY; BLOOD-GLUCOSE CONTROL; IV DP-IV; MYOCARDIAL-INFARCTION; CARDIOVASCULAR OUTCOMES; ISCHEMIA/REPERFUSION INJURY; SITAGLIPTIN IMPROVES; ENDOTHELIAL FUNCTION; DPP-4 INHIBITION AB Background and aims SAVOR-TIMI 53 was designed to study the effects of the DPP-4 inhibitor saxagliptin on cardiovascular outcomes in high risk type 2 diabetes patients with diverse levels of diabetes control and background anti-diabetic drugs. The goal of this article is to describe the baseline characteristics of this hypothesis driven study. Materials and methods A total of 16496 diabetic patients from North America (31.9%), Western Europe (26.0%), Eastern Europe (17.3%), Latin America (16.4%) and Asia (8.3%), with either established cardiovascular disease (78.3%) or with two additional cardiovascular risk factors (21.7%) were randomised to saxagliptin or placebo. Biomarkers of inflammation and insulin resistance were taken at baseline and 2years later in order to correlate saxagliptin effect on cardiovascular outcome to its effect on inflammation and insulin resistance. Results Mean [+/-standard deviation (SD)] age was 65.0 (+/-8.6)years, 66.9% were male, body mass index was 31.2kg/m(2) (+/-5.6), mean diabetes duration was 11.9years (+/-8.9) and the mean HbA(1c) 8.0% (+/-1.4%). HbA(1c)<7% was most prevalent among North Americans (30.8%) and least among Asians (15.1%), whereas HbA(1c)>9% was 30.7% in Latin America 27.0% in Asia and 15.1% in North America. Diabetic retinopathy was reported in 12.3% of patients, nephropathy in 17.7% and amputation in 2.5%. Diabetic treatments categories were as follows: no medication (5.4%), 1 oral anti-diabetic drug (OAD) (25.0%), 2 OAD (27.7%) and/or insulin (40.9%). The prevalence of micro-albuminuria was twice as high among insulin users compared with users of 2 OAD. Baseline statin use (78.3% overall) varied by region. Conclusion The SAVOR-TIMI 53 patient population, with differing background diabetes control and anti-diabetic treatment, provides global representation of diabetic patients with established cardiovascular disease or at high risk for cardiovascular disease and is well-positioned to determine the effect of saxagliptin on cardiovascular events. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Mosenzon, O.; Raz, I.] Hadassah Univ Hosp, Diabet Unit, Dept Med, IL-91120 Jerusalem, Israel. [Scirica, B. M.; Udell, J. A.; Braunwald, E.; Bhatt, D. L.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Scirica, B. M.; Udell, J. A.; Bhatt, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Hirshberg, B.; Ohman, P.; Price, D. L.] AstraZeneca Res & Dev, Wilmington, DE USA. [Stahre, C. I.] AstraZeneca Res & Dev, Molndal, Sweden. [Steg, P. G.] Univ Paris Diderot, Sorbonne Paris Cite, INSERM U698, CHU Bichat,AP HP, Paris, France. [Davidson, J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, Dallas, TX 75390 USA. [Frederich, B.] Bristol Myers Squibb Co, Princeton, NJ USA. [Bhatt, D. L.] VA Boston Healthcare Syst, Boston, MA USA. RP Raz, I (reprint author), Hadassah Univ Hosp, Diabet Unit, POB 12000, IL-91120 Jerusalem, Israel. EM ntv502@netvision.net.il FU AstraZeneca; Bristol-Myers Squibb FX SAVOR TIMI-53 is sponsored by AstraZeneca and Bristol-Myers Squibb. NR 56 TC 23 Z9 24 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD JUL PY 2013 VL 29 IS 5 BP 417 EP 426 DI 10.1002/dmrr.2413 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176UF UT WOS:000321330200014 PM 23564755 ER PT J AU Bastian, LA Bosworth, HB Washington, DL Yano, EM AF Bastian, Lori A. Bosworth, Hayden B. Washington, Donna L. Yano, Elizabeth M. TI Setting the Stage: Research to Inform Interventions, Practice and Policy to Improve Women Veterans' Health and Health Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Bastian, Lori A.] Univ Connecticut, Ctr Hlth, VA Connecticut Healthcare Syst, Newington, CT 06011 USA. [Bosworth, Hayden B.] Duke Univ, Durham VA Med Ctr, Durham, NC USA. [Washington, Donna L.] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bastian, LA (reprint author), Univ Connecticut, Ctr Hlth, VA Connecticut Healthcare Syst, 555 Willard Ave, Newington, CT 06011 USA. EM Lori.bastian@va.gov FU HSRD VA [SDR 10-012] NR 17 TC 6 Z9 6 U1 1 U2 6 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 JUL PY 2013 VL 28 SU 2 BP S491 EP S494 DI 10.1007/s11606-013-2470-9 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900001 PM 23807053 ER PT J AU Cordasco, KM Zephyrin, LC Kessler, CS Mallard, M Canelo, I Rubenstein, LV Yano, EM AF Cordasco, Kristina M. Zephyrin, Laurie C. Kessler, Chad S. Mallard, Meri Canelo, Ismelda Rubenstein, Lisa V. Yano, Elizabeth M. TI An Inventory of VHA Emergency Departments' Resources and Processes for Caring for Women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE veterans' health; women's health; emergency medicine; organization of care ID SEXUAL ASSAULT; VETERANS AB BACKGROUND: More women are using Veterans' Health Administration (VHA) Emergency Departments (EDs), yet VHA ED capacities to meet the needs of women are unknown. OBJECTIVE: We assessed VHA ED resources and processes for conditions specific to, or more common in, women Veterans. DESIGN/SUBJECTS: Cross-sectional questionnaire of the census of VHA ED directors MAIN MEASURES: Resources and processes in place for gynecologic, obstetric, sexual assault and mental health care, as well as patient privacy features, stratified by ED characteristics. KEY RESULTS: All 120 VHA EDs completed the questionnaire. Approximately nine out of ten EDs reported having gynecologic examination tables within their EDs, 24/7 access to specula, and Gonorrhea/Chlamydia DNA probes. All EDs reported 24/7 access to pregnancy testing. Fewer than two-fifths of EDs reported having radiologist review of pelvic ultrasound images available 24/7; one-third reported having emergent consultations from gynecologists available 24/7. Written transfer policies specific to gynecologic and obstetric emergencies were reported as available in fewer than half of EDs. Most EDs reported having emergency contraception 24/7; however, only approximately half reported having Rho(D) Immunoglobulin available 24/7. Templated triage notes and standing orders relevant to gynecologic conditions were reported as uncommon. Consistent with VHA policy, most EDs reported obtaining care for victims of sexual assault by transferring them to another institution. Most EDs reported having some access to private medical and mental health rooms. Resources and processes were found to be more available in EDs with more encounters by women, more ED staffed beds, and that were located in more complex facilities in metropolitan areas. CONCLUSIONS: Although most VHA EDs have resources and processes needed for delivering emergency care to women Veterans, some gaps exist. Studies in non-VA EDs are required for comparison. Creative solutions are needed to ensure that women presenting to VHA EDs receive efficient, timely, and consistently high-quality care. (C) Society of General Internal Medicine 2013 C1 [Cordasco, Kristina M.; Canelo, Ismelda; Rubenstein, Lisa V.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D Ctr Excellence Study, Los Angeles, CA 90073 USA. [Cordasco, Kristina M.; Rubenstein, Lisa V.; Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Cordasco, Kristina M.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Zephyrin, Laurie C.; Mallard, Meri] Vet Hlth Adm, Off Patient Care Serv, Womens Hlth Serv, Washington, DC USA. [Zephyrin, Laurie C.] VA New York Harbor Healthcare Syst, New York, NY USA. [Kessler, Chad S.] Durham VA Med Ctr, Durham, NC USA. [Kessler, Chad S.] Duke Univ, Sch Med, Durham, NC USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. RP Cordasco, KM (reprint author), VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D Ctr Excellence Study, 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. EM Kristina.Cordasco@va.gov FU VHA Office of Women's Health Services [XVA 65-027]; VA Women's Health Research Consortium [SDR 10-012]; VA HSR&D Research Career Scientist Award (RCS) [05-195] FX This project was funded by the VHA Office of Women's Health Services (Project # XVA 65-027), with in-kind support from the VA Women's Health Research Consortium (Project # SDR 10-012). Dr. Yano's effort was covered by a VA HSR&D Research Career Scientist Award (RCS #05-195). NR 14 TC 7 Z9 7 U1 1 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 JUL PY 2013 VL 28 SU 2 BP S583 EP S590 DI 10.1007/s11606-012-2327-7 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900017 PM 23807069 ER PT J AU Frayne, SM Carney, DV Bastian, L Bean-Mayberry, B Sadler, A Klap, R Phibbs, CS Kimerling, R Vogt, D Yee, EF Lin, JY Yano, EM AF Frayne, Susan M. Carney, Diane V. Bastian, Lori Bean-Mayberry, Bevanne Sadler, Anne Klap, Ruth Phibbs, Ciaran S. Kimerling, Rachel Vogt, Dawne Yee, Ellen F. Lin, Julia Y. Yano, Elizabeth M. TI The VA Women's Health Practice-Based Research Network: Amplifying Women Veterans' Voices in VA Research SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID RESEARCH AGENDA; CARE C1 [Frayne, Susan M.; Carney, Diane V.; Phibbs, Ciaran S.; Kimerling, Rachel] VA Palo Alto Hlth Care Syst, VA HSR&D Ctr Excellence, Palo Alto, CA USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. [Frayne, Susan M.; Phibbs, Ciaran S.] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. [Bastian, Lori] VA Med Ctr, VA HSR&D Ctr Excellence, Durham, NC USA. [Bastian, Lori] Univ Connecticut, Ctr Hlth, Div Gen Internal Med, Farmington, CT USA. [Bean-Mayberry, Bevanne; Klap, Ruth; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence, Sepulveda, CA USA. [Bean-Mayberry, Bevanne] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Sadler, Anne] Iowa City VA Hlth Care Syst, Mental Hlth Serv Line, VA HSR&D Ctr Comprehens Access & Delivery Res & E, Iowa City, IA USA. [Sadler, Anne] Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. [Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Palo Alto, CA USA. [Phibbs, Ciaran S.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Vogt, Dawne] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. [Yee, Ellen F.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [Yee, Ellen F.] Univ New Mexico, Albuquerque, NM 87131 USA. [Lin, Julia Y.] VA Palo Alto Hlth Care Syst, VA Cooperat Studies Program Coordinating Ctr, Palo Alto, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Frayne, SM (reprint author), VA Palo Alto Hlth Care Syst, VA HSR&D Ctr Excellence, Palo Alto, CA USA. EM susan.frayne@va.gov OI Kimerling, Rachel/0000-0003-0996-4212 NR 16 TC 16 Z9 16 U1 0 U2 3 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 JUL PY 2013 VL 28 SU 2 BP S504 EP S509 DI 10.1007/s11606-013-2476-3 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900005 PM 23807057 ER PT J AU Hamilton, AB Frayne, SM Cordasco, KM Washington, DL AF Hamilton, Alison B. Frayne, Susan M. Cordasco, Kristina M. Washington, Donna L. TI Factors Related to Attrition from VA Healthcare Use: Findings from the National Survey of Women Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Veterans; women's health; access to care; attrition ID MILITARY SEXUAL TRAUMA; PATIENT SATISFACTION; MEDICAL-CARE; CONTINUITY; SERVICES; PERCEPTIONS; POPULATION; PROVIDER; QUALITY; AFFAIRS AB BACKGROUND: While prior research characterizes women Veterans' barriers to accessing and using Veterans Health Administration (VA) care, there has been little attention to women who access VA and use services, but then discontinue use. Recent data suggest that among women Veterans, there is a 30 % attrition rate within 3 years of initial VA use. OBJECTIVES: To compare individual characteristics and perceptions about VA care between women Veteran VA attriters (those who discontinue use) and non-attriters (those who continue use), and to compare recent versus remote attriters. DESIGN: Cross-sectional, population-based 20082009 national telephone survey. PARTICIPANTS: Six hundred twenty-six attriters and 2,065 non-attriters who responded to the National Survey of Women Veterans. MAIN MEASURES: Population weighted demographic, military and health characteristics; perceptions about VA healthcare; length of time since last VA use; among attriters, reasons for no longer using VA care. KEY RESULTS: Fifty-four percent of the weighted VA ever user population reported that they no longer use VA. Forty-five percent of attrition was within the past ten years. Attriters had better overall health (p=0.007), higher income (p<0.001), and were more likely to have health insurance (p<0.001) compared with non-attriters. Attriters had less positive perceptions of VA than non-attriters, with attriters having lower ratings of VA quality and of gender-specific features of VA care (p<0.001). Women Veterans who discontinued VA use since 2001 did not differ from those with more remote VA use on most measures of VA perceptions. Overall, among attriters, distance to VA sites of care and having alternate insurance coverage were the most common reasons for discontinuing VA use. CONCLUSIONS: We found high VA attrition despite recent advances in VA care for women Veterans. Women's attrition from VA could reduce the critical mass of women Veterans in VA and affect current system-wide efforts to provide high-quality care for women Veterans. An understanding of reasons for attrition can inform organizational efforts to re-engage women who have attrited, to retain current users, and potentially to attract new VA patients. (C) Society of General Internal Medicine 2013 C1 [Hamilton, Alison B.; Cordasco, Kristina M.; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Frayne, Susan M.] VA Palo Alto Healthcare Syst, VA HSR&D Ctr Excellence, Palo Alto, CA USA. [Frayne, Susan M.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Cordasco, Kristina M.] RAND Corp, Santa Monica, CA USA. [Cordasco, Kristina M.; Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Hamilton, AB (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSRD Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. EM alison.hamilton@va.gov FU Department of Veterans Affairs (VA), Women's Health Services within the Office of Patient Care Services; VA Health Services Research and Development (HSRD) Service [SDR-08-270] FX This study was funded by the Department of Veterans Affairs (VA), Women's Health Services within the Office of Patient Care Services, and the VA Health Services Research and Development (HSR&D) Service (SDR-08-270). NR 34 TC 15 Z9 15 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2013 VL 28 SU 2 BP S510 EP S516 DI 10.1007/s11606-013-2347-y PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900006 PM 23807058 ER PT J AU Katon, J Reiber, G Rose, D Bean-Mayberry, B Zephyrin, L Washington, DL Yano, EM AF Katon, Jodie Reiber, Gayle Rose, Danielle Bean-Mayberry, Bevanne Zephyrin, Laurie Washington, Donna L. Yano, Elizabeth M. TI VA Location and Structural Factors Associated with On-Site Availability of Reproductive Health Services SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women veterans; reproductive health; reproductive health services; Department of Veterans Affairs ID OF-VETERANS-AFFAIRS; PRIMARY-CARE; WOMEN VETERANS; OUTPATIENT CLINICS; MEDICAL-CENTER AB INTRODUCTION: With the increasing number of women Veterans enrolling in the Veterans Health Administration (VA), there is growing demand for reproductive health services. Little is known regarding the on-site availability of reproductive health services at VA and how this varies by site location and type. OBJECTIVE: To describe the on-site availability of hormonal contraception, intrauterine device (IUD) placement, infertility evaluation or treatment, and prenatal care by site location and type; the characteristics of sites providing these services; and to determine whether, within this context, site location and type is associated with on-site availability of these reproductive health services. METHODS: We used data from the 2007 Veterans Health Administration Survey of Women Veterans Health Programs and Practices, a national census of VA sites serving 300 or more women Veterans assessing practice structure and provision of care for women. Hierarchical models were used to test whether site location and type (metropolitan hospital-based clinic, non-metropolitan hospital-based clinic, metropolitan community-based outpatient clinic [CBOC]) were associated with availability of IUD placement and infertility evaluation/treatment. Non-metropolitan CBOCs were excluded from this analysis (n=2). RESULTS: Of 193 sites, 182 (94 %) offered on-site hormonal contraception, 97 (50 %) offered on-site IUD placement, 57 (30 %) offered on-site infertility evaluation/treatment, and 11 (6 %) offered on-site prenatal care. After adjustment, compared with metropolitan hospital based-clinics, metropolitan CBOCs were less likely to offer on-site IUD placement (OR 0.33; 95 % CI 0.14, 0.74). CONCLUSION: Compared with metropolitan hospital-based clinics, metropolitan CBOCs offer fewer specialized reproductive health services on-site. Additional research is needed regarding delivery of specialized reproductive health care services for women Veterans in CBOCs and clinics in non-metropolitan areas. (C) Society of General Internal Medicine 2012 C1 [Katon, Jodie; Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Vet Affairs VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Katon, Jodie; Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98108 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98108 USA. [Rose, Danielle; Bean-Mayberry, Bevanne; Washington, Donna L.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Provider Be, Los Angeles, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Zephyrin, Laurie] VA Cent Off, Off Patient Serv, Women Vet Hlth Serv, Washington, DC USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Katon, J (reprint author), Univ Washington, Sch Publ Hlth, Dept Vet Affairs VA Puget Sound Hlth Care Syst, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM jkaton@u.washington.edu FU U.S. Department of Veteran Affairs, Office of Research and Development, Health Services Research and Development [IIR 04-036]; WHR Consortium [10-012]; Office of Academic Affiliations [TPP 61-026]; VA HSR&D Senior Career Scientist Award [RCS 98-353]; VA HSR&D Career Scientist Award [RCS 05-195] FX This material is based on work supported by the U.S. Department of Veteran Affairs, Office of Research and Development, Health Services Research and Development (grant IIR 04-036) and the WHR Consortium (Project SDR# 10-012), an Office of Academic Affiliations' Associated Health Postdoctoral Fellowship to Dr. Katon (#TPP 61-026), a VA HSR&D Senior Career Scientist Award to Dr. Reiber (grant RCS 98-353) and a VA HSR&D Career Scientist Award to Dr. Yano (grant RCS 05-195). The authors would like to thank Ismelda Canelo for her work managing the data. 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. NR 19 TC 9 Z9 9 U1 0 U2 7 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 JUL PY 2013 VL 28 SU 2 BP S591 EP S597 DI 10.1007/s11606-012-2289-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900018 PM 23807070 ER PT J AU Lehavot, K Simpson, TL AF Lehavot, Keren Simpson, Tracy L. TI Incorporating Lesbian and Bisexual Women into Women Veterans' Health Priorities SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women veterans; lesbian and bisexual women; sexual minority veterans ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ORIENTATION DISCLOSURE; NATIONAL COMORBIDITY SURVEY; POPULATION-BASED SURVEY; HETEROSEXUAL WOMEN; FEMALE VETERANS; MENTAL-HEALTH; PROBABILITY SAMPLE; MINORITY ADULTS; CIVILIAN WOMEN AB Relative to the general population, lesbian and bisexual (LB) women are overrepresented in the military and are significantly more likely to have a history of military service compared to all adult women. Due to institutional policies and stigma associated with a gay or lesbian identity, very little empirical research has been done on this group of women veterans. Available data suggest that compared to heterosexual women veterans, LB women veterans are likely to experience heightened levels of prejudice and discrimination, victimization, including greater incidence of rape, as well as adverse health and substance use disorders. They are also likely to encounter a host of unique issues when accessing health care, including fears of insensitive care and difficulty disclosing sexual orientation to Veterans Health Administration (VHA) providers. Training of staff and providers, education efforts, outreach activities, and research on this subpopulation are critical to ensure equitable and high quality service delivery. C1 [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,116 POC, Seattle, WA 98108 USA. EM klehavot@uw.edu FU Department of Veterans Affairs Office of Academic Affiliations; Advanced Fellowship Program in Mental Illness Research and Treatment; VA Puget Sound Health Care System, Seattle, Washington FX This material is the result of work supported by resources from the Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, and the VA Puget Sound Health Care System, Seattle, Washington. The views expressed in this article are those of the authors and do not represent the views of the Department of Veterans Affairs or the United States government. NR 68 TC 11 Z9 11 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2013 VL 28 SU 2 BP S609 EP S614 DI 10.1007/s11606-012-2291-2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900021 PM 23807073 ER PT J AU Maguen, S Madden, E Cohen, B Bertenthal, D Neylan, T Talbot, L Grunfeld, C Seal, K AF Maguen, Shira Madden, Erin Cohen, Beth Bertenthal, Daniel Neylan, Thomas Talbot, Lisa Grunfeld, Carl Seal, Karen TI The Relationship between Body Mass Index and Mental Health Among Iraq and Afghanistan Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health; veteran; mental health; obesity ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY VETERANS; WOMEN VETERANS; OBESITY; DIAGNOSES; RISK; CARE; OVERWEIGHT; SAMPLE; BMI AB BACKGROUND: Obesity is a growing public health concern and is becoming an epidemic among veterans in the post-deployment period. OBJECTIVE: To explore the relationship between body mass index (BMI) and posttraumatic stress disorder (PTSD) in a large cohort of Iraq and Afghanistan veterans, and to evaluate trajectories of change in BMI over 3 years. DESIGN: Retrospective, longitudinal cohort analysis of veterans' health records PARTICIPANTS: A total of 496,722 veterans (59,790 female and 436,932 male veterans) whose height and weight were recorded at the Department of Veterans Affairs (VA) healthcare system at least once after the end of their last deployment and whose first post-deployment outpatient encounter at the VA was at least 1 year prior to the end of the study period (December 31, 2011). MAIN MEASURES: BMI, mental health diagnoses. KEY RESULTS: Seventy-five percent of Iraq and Afghanistan veterans were either overweight or obese at baseline. Four trajectories were observed: "stable overweight" represented the largest class; followed by "stable obese;" "overweight/obese gaining;" and "obese losing." During the 3-year ascertainment period, those with PTSD and depression in particular were at the greatest risk of being either obese without weight loss or overweight or obese and continuing to gain weight. Adjustment for demographics and antipsychotic medication attenuated the relationship between BMI and certain mental health diagnoses. Although BMI trajectories were similar in men and women, some gender differences were observed. For example, the risk of being in the persistently obese class in men was highest for those with PTSD, whereas for women, the risk was highest among those with depression. CONCLUSIONS: The growing number of overweight or obese returning veterans is a concerning problem for clinicians who work with these patients. Successful intervention to reduce the prevalence of obesity will require integrated efforts from primary care and mental health to treat underlying mental health causes and assist with engagement in weight loss programs. (C) Society of General Internal Medicine 2013 C1 [Maguen, Shira; Madden, Erin; Cohen, Beth; Bertenthal, Daniel; Neylan, Thomas; Talbot, Lisa; Grunfeld, Carl; Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Neylan, Thomas; Talbot, Lisa; Seal, Karen] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth; Grunfeld, Carl; Seal, Karen] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bertenthal, Daniel] Mental Illness Res Educ & Clin Ctr, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116-P, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov FU Department of Defense; VA Health Sciences Research and Development (HSR&D) Career Development Award; National Institutes of Health [K23 HL 094765-01]; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration FX This research was supported by Department of Defense Concept Award Grant (Maguen), VA Health Sciences Research and Development (HSR&D) Career Development Award (Maguen), National Institutes of Health grant K23 HL 094765-01 (Cohen), and the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration. NR 33 TC 20 Z9 20 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2013 VL 28 SU 2 BP S563 EP S570 DI 10.1007/s11606-013-2374-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900014 PM 23807066 ER PT J AU Mattocks, KM Sadler, A Yano, EM Krebs, EE Zephyrin, L Brandt, C Kimerling, R Sandfort, T Dichter, ME Weiss, JJ Allison, J Haskell, S AF Mattocks, Kristin M. Sadler, Anne Yano, Elizabeth M. Krebs, Erin E. Zephyrin, Laurie Brandt, Cynthia Kimerling, Rachel Sandfort, Theo Dichter, Melissa E. Weiss, Jeffrey J. Allison, Jeroan Haskell, Sally TI Sexual Victimization, Health Status, and VA Healthcare Utilization Among Lesbian and Bisexual OEF/OIF Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE lesbian; health services research; Veterans; women ID MENTAL-HEALTH; RISK-FACTORS; AFGHANISTAN; TRAUMA; FEMALE; IRAQ AB BACKGROUND: Many lesbian and bisexual (LB) women veterans may have been targets of victimization in the military based on their gender and presumed sexual orientation, and yet little is known regarding the health or mental health of LB veterans, nor the degree to which they feel comfortable receiving care in the VA. OBJECTIVE: The purpose of this study was to examine the prevalence of mental health and gender-specific conditions, VA healthcare satisfaction and trauma exposure among LB veterans receiving VA care compared with heterosexually-identified women veterans receiving. DESIGN: Prospective cohort study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) women veterans at two large VA facilities. PARTICIPANTS: Three hundred and sixty five women veterans that completed a baseline survey. Thirty-five veterans (9.6 %) identified as gay or lesbian (4.7 %), or bisexual (4.9 %). MAIN MEASURES: Measures included sexual orientation, military sexual trauma, mental and gender-specific health diagnoses, and VA healthcare utilization and satisfaction. KEY RESULTS: LB OEF/OIF veterans were significantly more likely to have experienced both military and childhood sexual trauma than heterosexual women (MST: 31 % vs. 13 %, p<.001; childhood sexual trauma: 60 % vs. 36 %, p=.01), to be hazardous drinkers (32 % vs. 16 %, p=.03) and rate their current mental health as worse than before deployment (35 % vs. 16 %, p<.001). CONCLUSIONS: Many LB veterans have experienced sexual victimization, both within the military and as children, and struggle with substance abuse and poor mental health. Health care providers working with female Veterans should be aware of high rates of military sexual trauma and childhood abuse and refer women to appropriate VA treatment and support groups for sequelae of these experiences. Future research should focus on expanding this study to include a larger and more diverse sample of lesbian, gay, bisexual, and transgender veterans receiving care at VA facilities across the country. (C) Society of General Internal Medicine 2013 C1 [Mattocks, Kristin M.] VA Cent Western Massachusetts, Leeds, MA 01053 USA. [Mattocks, Kristin M.; Allison, Jeroan] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Sadler, Anne] Iowa City VA Hlth Care Syst, CADRE, Mental Hlth Serv Line, Iowa City, IA USA. [Sadler, Anne] Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. [Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Excellence Study, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Krebs, Erin E.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Krebs, Erin E.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Zephyrin, Laurie] Dept Vet Affairs, Washington, DC USA. [Brandt, Cynthia; Haskell, Sally] VA Connecticut Healthcare Syst, West Haven, CT USA. [Brandt, Cynthia; Haskell, Sally] Yale Univ, Sch Med, New Haven, CT USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Sandfort, Theo] Columbia Univ, HIV Ctr Clin & Behav Studies, New York, NY USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. [Weiss, Jeffrey J.] Mt Sinai Sch Med, Div Gen Internal Med, Dept Med, New York, NY USA. RP Mattocks, KM (reprint author), VA Cent Western Massachusetts Healthcare Syst, 421 North Main St, Leeds, MA 01053 USA. EM Kristin.mattocks@va.gov OI Kimerling, Rachel/0000-0003-0996-4212; Allison, Jeroan/0000-0003-4472-2112 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA Health Services Research & Development (HSR&D) Service Senior Research Career Scientist Award (RCS) [05-195] FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. 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 Stated Government. Dr. Yano's time was supported by a VA Health Services Research & Development (HSR&D) Service Senior Research Career Scientist Award (RCS #05-195). NR 18 TC 16 Z9 16 U1 2 U2 16 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 JUL PY 2013 VL 28 SU 2 BP S604 EP S608 DI 10.1007/s11606-013-2357-9 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900020 PM 23807072 ER PT J AU Rose, DE Farmer, MM Yano, EM Washington, DL AF Rose, Danielle E. Farmer, Melissa M. Yano, Elizabeth M. Washington, Donna L. TI Racial/Ethnic Differences in Cardiovascular Risk Factors Among Women Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cardiovascular disease; risk factors; race; ethnicity; women veterans ID QUALITY-OF-CARE; SMOKING; DISEASE; UPDATE; SYSTEM AB BACKGROUND: Heart disease is the leading cause of death for women in the United States, accounting for 24.5 % of all deaths among women. Earlier research has demonstrated racial/ethnic differences in prevalence of cardiovascular (CVD) risk factors. OBJECTIVE: To empirically examine the prevalence of CVD risk factors among a national sample of women Veterans by race/ethnicity, providing the first portrait of women Veterans' cardiovascular care needs. DESIGN AND PARTICIPANTS: Cross-sectional, national population-based telephone survey of 3,611 women Veterans. MEASUREMENTS: Women Veterans were queried about presence of diabetes, hypertension, obesity, tobacco use and physical activity. Four racial/ethnic categories were created: Hispanic, Non-Hispanic White (White), Non-Hispanic Black (Black), and Other. Logistic regressions were conducted for each risk factor to test for racial/ethnic differences, controlling for age (under 40 vs. 40 and over). KEY RESULTS: Racial/ethnic differences in CVD risk factors persisted after adjusting for age. Black women Veterans were more likely to report a diagnosis of diabetes (OR: 2.58, 95 % CI: 1.07, 6.21) or hypertension (OR: 2.31, 95 % CI: 1.10, 4.83) and be obese (OR: 2.06, 95 % CI: 1.05, 3.91) than White women Veterans. Hispanic women Veterans were more likely than White women Veterans to report diabetes (OR: 4.20, 95 % CI: 1.15, 15.39) and daily smoking (OR: 3.38, 95 % CI: 1.01, 11.30), but less likely to report a hypertension diagnosis (OR 0.21, 95% CI: 0.07, 0.64) or to be obese (OR: 0.39, 95 % CI: 0.18, 0.81). CONCLUSIONS: Among women Veterans, CVD risks vary by race/ethnicity. Black women Veterans consistently face higher CVD risk compared to White women Veterans, while results are mixed for Hispanic women Veterans. (C) Society of General Internal Medicine 2013 C1 [Rose, Danielle E.; Farmer, Melissa M.; Yano, Elizabeth M.; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D Ctr Excellence Study, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Rose, DE (reprint author), VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D Ctr Excellence Study, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM Danielle.Rose@va.gov FU Department of Veterans Affairs (VA) Women's Health Services in the Office of Patient Care Services; VA Health Services Research and Development (HSRD) Service [SDR 08-270]; VA HSR&D Senior Research Career Scientist award [RCS 05-195] FX This study was funded by the Department of Veterans Affairs (VA) Women's Health Services in the Office of Patient Care Services, and the VA Health Services Research and Development (HSR&D) Service (#SDR 08-270). Dr. Yano was supported by a VA HSR&D Senior Research Career Scientist award (#RCS 05-195). The authors gratefully acknowledge Mark Canning for project management, Julia Yosef, MA for assistance with survey fieldwork, Su Sun, MPH for assistance with data management, and Michael Mitchell, PhD, for statistical assistance. The views expressed within are solely those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs or the United States government. NR 17 TC 7 Z9 7 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2013 VL 28 SU 2 BP S524 EP S528 DI 10.1007/s11606-012-2309-9 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900008 PM 23807060 ER PT J AU Street, AE Gradus, JL Giasson, HL Vogt, D Resick, PA AF Street, Amy E. Gradus, Jaimie L. Giasson, Hannah L. Vogt, Dawne Resick, Patricia A. TI Gender Differences Among Veterans Deployed in Support of the Wars in Afghanistan and Iraq SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE veteran; women; sexual harassment; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY SEXUAL TRAUMA; US ARMY SOLDIERS; MENTAL-HEALTH; PTSD SYMPTOMS; DEPRESSION; COMBAT; ASSAULT; RISK; EXPERIENCES AB BACKGROUND: The changing scope of women's roles in combat operations has led to growing interest in women's deployment experiences and post-deployment adjustment. OBJECTIVES: To quantify the gender-specific frequency of deployment stressors, including sexual and nonsexual harassment, lack of social support and combat exposure. To quantify gender-specific post-deployment mental health conditions and associations between deployment stressors and posttraumatic stress disorder (PTSD), to inform the care of Veterans returning from the current conflicts. DESIGN: National mail survey of OEF/OIF Veterans randomly sampled within gender, with women over-sampled. SETTING: The community. PARTICIPANTS: In total, 1,207 female and 1,137 male Veterans from a roster of all Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. Response rate was 48.6 %. MAIN MEASURES: Deployment stressors (including combat and harassment stress), PTSD, depression, anxiety and alcohol use, all measured via self-report. KEY RESULTS: Women were more likely to report sexual harassment (OR=8.7, 95% CI: 6.9, 11) but less likely to report combat (OR= 0.62, 95 % CI: 0.50, 0.76). Women and men were equally likely to report symptoms consistent with probable PTSD (OR = 0.87, 95 % CI: 0.70, 1.1) and symptomatic anxiety (OR = 1.1, 9 5% CI: 0.86, 1.3). Women were more likely to report probable depression (OR= 1.3, 95 % CI: 1.1, 1.6) and less likely to report problematic alcohol use (OR = 0.59, 9 5% CI: 0.47, 0.72). With a five-point change in harassment stress, adjusted odds ratios for PTSD were 1.36 (95 % CI: 1.23, 1.52) for women and 1.38 (95 % CI: 1.19, 1.61) for men. The analogous associations between combat stress and PTSD were 1.31 (95 % CI: 1.24, 1.39) and 1.31 (95 % CI: 1.26, 1.36), respectively. CONCLUSIONS: Although there are important gender differences in deployment stressors-including women's increased risk of interpersonal stressors- and post-deployment adjustment, there are also significant similarities. The post-deployment adjustment of our nation's growing population of female Veterans seems comparable to that of our nation's male Veterans. (C) Society of General Internal Medicine 2013 C1 [Street, Amy E.; Gradus, Jaimie L.; Giasson, Hannah L.; Vogt, Dawne; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Street, Amy E.; Gradus, Jaimie L.; Vogt, Dawne; 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. RP Street, AE (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 South Huntington Ave,116B-3, Boston, MA 02130 USA. EM amy.street@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU National Center for PTSD, Office of Mental Health Services, Department of Veterans Affairs FX This research was supported by the National Center for PTSD, Office of Mental Health Services, Department of Veterans Affairs. 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. The funding agency was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 43 TC 42 Z9 42 U1 1 U2 23 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 JUL PY 2013 VL 28 SU 2 BP S556 EP S562 DI 10.1007/s11606-013-2333-4 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900013 PM 23807065 ER PT J AU Washington, DL Bean-Mayberry, B Hamilton, AB Cordasco, KM Yano, EM AF Washington, Donna L. Bean-Mayberry, Bevanne Hamilton, Alison B. Cordasco, Kristina M. Yano, Elizabeth M. TI Women Veterans' Healthcare Delivery Preferences and Use by Military Service Era: Findings from the National Survey of Women Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women Veterans; VA healthcare; health services need; health services utilization; health care preferences ID GENDER-DIFFERENCES; VA; ILLNESS AB BACKGROUND: The number of women Veterans (WVs) utilizing the Veterans Health Administration (VA) has doubled over the past decade, heightening the importance of understanding their healthcare delivery preferences and utilization patterns. Other studies have identified healthcare issues and behaviors of WVs in specific military service eras (e. g., Vietnam), but delivery preferences and utilization have not been examined within and across eras on a population basis. OBJECTIVE: To identify healthcare delivery preferences and healthcare use of WVs by military service era to inform program design and patient-centeredness. DESIGN AND PARTICIPANTS: Cross-sectional 2008-2009 survey of a nationally representative sample of 3,611 WVs, weighted to the population. MAIN MEASURES: Healthcare delivery preferences measured as importance of selected healthcare features; types of healthcare services and number of visits used; use of VA or non-VA; all by military service era. KEY RESULTS: Military service era differences were present in types of healthcare used, with World War II and Korea era WVs using more specialty care, and Vietnam era-to-present WVs using more women's health and mental health care. Operations Enduring Freedom, Iraqi Freedom, New Dawn (OEF/OIF/OND) WVs made more healthcare visits than WVs of earlier military eras. The greatest healthcare delivery concerns were location convenience for Vietnam and earlier WVs, and cost for Gulf War 1 and OEF/OIF/OND WVs. Co-located gynecology with general healthcare was also rated important by a sizable proportion of WVs from all military service eras. CONCLUSIONS: Our findings point to the importance of ensuring access to specialty services closer to home for WVs, which may require technology-supported care. Younger WVs' higher mental health care use reinforces the need for integration and coordination of primary care, reproductive health and mental health care. (C) Society of General Internal Medicine 2013 C1 [Washington, Donna L.; Bean-Mayberry, Bevanne; Hamilton, Alison B.; Cordasco, Kristina M.; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Ctr Excellence Study Healthcare Provider Behav, Sepulveda, CA USA. [Washington, Donna L.; Bean-Mayberry, Bevanne; Cordasco, Kristina M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Cordasco, Kristina M.] RAND Corp, Santa Monica, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM Donna.washington@va.gov FU Department of Veterans Affairs (VA) Women's Health Services in the Office of Patient Care Services; VA Health Services Research and Development (HSRD) Service [SDR-08-270]; VA HSR&D Research Career Scientist award [RCS-05-195]; VA HSR&D Research Career Development Transition award [RCD 02-039] FX This study was funded by the Department of Veterans Affairs (VA) Women's Health Services in the Office of Patient Care Services, and the VA Health Services Research and Development (HSR&D) Service (#SDR-08-270). Dr. Yano is supported by a VA HSR&D Research Career Scientist award (#RCS-05-195). Dr. Bean-Mayberry was supported by a VA HSR&D Research Career Development Transition award (#RCD 02-039) during this study. The views expressed within are solely those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs or the United States government. NR 28 TC 26 Z9 26 U1 1 U2 10 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 JUL PY 2013 VL 28 SU 2 BP S571 EP S576 DI 10.1007/s11606-012-2323-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900015 PM 23807067 ER PT J AU Yan, GW McAndrew, L D'Andrea, EA Lange, G Santos, SL Engel, CC Quigley, KS AF Yan, Grace W. McAndrew, Lisa D'Andrea, Elizabeth A. Lange, Gudrun Santos, Susan L. Engel, Charles C. Quigley, Karen S. TI Self-Reported Stressors of National Guard Women Veterans Before and After Deployment: The Relevance of Interpersonal Relationships SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health; veterans; survey research; quality of life ID MILITARY SEXUAL TRAUMA; COMBAT; WAR; CARE; RISK; IRAQ AB BACKGROUND: With their rapidly expanding roles in the military, women service members experience significant stressors throughout their deployment experience. However, there are few studies that examine changes in women Veterans' stressors before and after deployment. OBJECTIVE: This study examines the types of stressors women Veterans report before deployment, immediately after deployment, 3 months after deployment, and 1 year post-deployment. DESIGN: Descriptive data on reported stressors was collected at four time points of a longitudinal study (HEROES Project). Open-ended responses from the Coping Response Inventory (CRI) were coded into six possible major stressor categories for analysis. PARTICIPANTS: Seventy-nine Army National Guard and Reserve female personnel deploying to Operation Enduring Freedom (OFF)/Operation Iraqi Freedom (OIF) were surveyed prior to deployment. Of these participants, 35 women completed Phase 2, 41 completed Phase 3, and 48 completed Phase 4 of the study. KEY RESULTS: We identified six major stressor categories: (1) interpersonal (i.e., issues with family and/or friends), (2) deployment-related and military-related, (3) health concerns, (4) death of a loved one, (5) daily needs (i. e., financial/housing/transportation concerns), and (6) employment or school-related concerns. At all time points, interpersonal issues were one of the most common type of stressor for this sample. Daily needs concerns increased from 3 months post-deployment to 1 year post-deployment. CONCLUSIONS: Interpersonal concerns are commonly reported by women Veterans both before and after their combat experience, suggesting that this is a time during which interpersonal support is especially critical. We discuss implications, which include the need for a more coordinated approach to women Veterans' health care (e. g., greater community-based outreach), and the need for more and more accessible Veterans Affairs (VA) services to address the needs of female Veterans. (C) Society of General Internal Medicine 2012 C1 [Yan, Grace W.; McAndrew, Lisa; D'Andrea, Elizabeth A.; Lange, Gudrun; Santos, Susan L.] NJ War Related Illness & Injury Study Ctr, Dept Vet Affairs, E Orange, NJ USA. [McAndrew, Lisa; Lange, Gudrun] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [D'Andrea, Elizabeth A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Santos, Susan L.] Univ Med & Dent New Jersey, Sch Publ Hlth, Piscataway, NJ 08854 USA. [Engel, Charles C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Washington, DC USA. [Engel, Charles C.] Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Bethesda, MD USA. [Quigley, Karen S.] Edith Nourse Rogers Mem Vet Adm Hosp, Dept Vet Affairs, Bedford, MA 01730 USA. [Quigley, Karen S.] Northeastern Univ, Boston, MA 02115 USA. RP Yan, GW (reprint author), NJ War Related Illness Injury Study Ctr, Dept Vet Affairs, 385 Tremont Ave,Mailstop 129, E Orange, NJ 07018 USA. EM weiyin.yan@va.gov FU Department of Veterans Affairs, Health Services Research & Development Service [IIR 02-296]; NJ War Related Illness and Injury Study Center, the NJ REAP [REA 03-021]; Deployment Health Clinical Center, Walter Reed Army Medical Center FX This study was supported by grants from the Department of Veterans Affairs, Health Services Research & Development Service (IIR 02-296 to K. Quigley); the NJ War Related Illness and Injury Study Center, the NJ REAP (REA 03-021); and the Deployment Health Clinical Center, Walter Reed Army Medical Center. NR 20 TC 5 Z9 5 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2013 VL 28 SU 2 BP S549 EP S555 DI 10.1007/s11606-012-2247-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 184RL UT WOS:000321910900012 PM 23807064 ER PT J AU Kalluri, R Shera, CA AF Kalluri, Radha Shera, Christopher A. TI Measuring stimulus-frequency otoacoustic emissions using swept tones SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID COHERENT REFLECTION; HUMANS; MECHANICS; DELAYS; LEVEL; EARS AB Although stimulus-frequency otoacoustic emissions (SFOAEs) offer compelling advantages as noninvasive probes of cochlear function, they remain underutilized compared to other evoked emission types, such as distortion-products (DPOAEs), whose measurement methods are less complex and time-consuming. Motivated by similar advances in the measurement of DPOAEs, this paper develops and characterizes a more efficient SFOAE measurement paradigm based on swept tones. In contrast to standard SFOAE measurement methods, in which the emissions are measured in the sinusoidal steady-state using discrete tones of well defined frequency, the swept-tone method sweeps rapidly across frequency (typically at rates of 1 Hz/ms or greater) using a chirp-like stimulus. Measurements obtained using both swept-and discrete-tone methods in an interleaved suppression paradigm demonstrate that the two methods of measuring SFOAEs yield nearly equivalent results, the differences between them being comparable to the run-to-run variability encountered using either method alone. The match appears robust to variations in measurement parameters, such as sweep rate and direction. The near equivalence of the SFOAEs obtained using the two measurement methods enables the interpretation of swept-tone SFOAEs within existing theoretical frameworks. Furthermore, the data demonstrate that SFOAE phase-gradient delays-including their large and irregular fluctuations across frequency-reflect actual physical time delays at different frequencies, showing that the physical emission latency, not merely the phase gradient, is inherently irregular. (C) 2013 Acoustical Society of America. C1 [Kalluri, Radha] House Ear Res Inst, Div Commun & Auditory Neurosci, Los Angeles, CA 90057 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM christopher.shera@gmail.com FU National Institutes of Health [R01 DC03687, P30 DC05209, P30 DC10743] FX We thank Carolina Abdala and John Guinan for their helpful comments on the manuscript. This work was supported by grants R01 DC03687, P30 DC05209, and P30 DC10743 from the National Institutes of Health. NR 25 TC 20 Z9 20 U1 1 U2 5 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2013 VL 134 IS 1 BP 356 EP 368 DI 10.1121/1.4807505 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 184QQ UT WOS:000321908500056 PM 23862813 ER PT J AU John, SP Chin, CR Perreira, JM Feeley, EM Aker, AM Savidis, G Smith, SE Elia, AEH Everitt, AR Vora, M Pertel, T Elledge, SJ Kellam, P Brass, AL AF John, Sinu P. Chin, Christopher R. Perreira, Jill M. Feeley, Eric M. Aker, Aaron M. Savidis, George Smith, Sarah E. Elia, Andrew E. H. Everitt, Aaron R. Vora, Mehul Pertel, Thomas Elledge, Stephen J. Kellam, Paul Brass, Abraham L. TI The CD225 Domain of IFITM3 Is Required for both IFITM Protein Association and Inhibition of Influenza A Virus and Dengue Virus Replication SO JOURNAL OF VIROLOGY LA English DT Article ID WEST NILE VIRUS; ANTIVIRAL ACTIVITY; MEMBRANE FISSION; S-PALMITOYLATION; INFECTION; IDENTIFICATION; RESISTANCE; FUSION; FORCES AB The interferon-induced transmembrane protein 3 (IFITM3) gene is an interferon-stimulated gene that inhibits the replication of multiple pathogenic viruses in vitro and in vivo. IFITM3 is a member of a large protein superfamily, whose members share a functionally undefined area of high amino acid conservation, the CD225 domain. We performed mutational analyses of IFITM3 and identified multiple residues within the CD225 domain, consisting of the first intramembrane domain (intramembrane domain 1 [IM1]) and a conserved intracellular loop (CIL), that are required for restriction of both influenza A virus (IAV) and dengue virus (DENV) infection in vitro. Two phenylalanines within IM1 (F75 and F78) also mediate a physical association between IFITM proteins, and the loss of this interaction decreases IFITM3-mediated restriction. By extension, similar IM1-mediated associations may contribute to the functions of additional members of the CD225 domain family. IFITM3's distal N-terminal domain is also needed for full antiviral activity, including a tyrosine (Y20), whose alteration results in mislocalization of a portion of IFITM3 to the cell periphery and surface. Comparative analyses demonstrate that similar molecular determinants are needed for IFITM3's restriction of both IAV and DENV. However, a portion of the CIL including Y99 and R87 is preferentially needed for inhibition of the orthomyxovirus. Several IFITM3 proteins engineered with rare single-nucleotide polymorphisms demonstrated reduced expression or mislocalization, and these events were associated with enhanced viral replication in vitro, suggesting that possessing such alleles may impact an individual's risk for viral infection. On the basis of this and other data, we propose a model for IFITM3-mediated restriction. C1 [John, Sinu P.; Chin, Christopher R.; Perreira, Jill M.; Aker, Aaron M.; Savidis, George; Vora, Mehul; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01605 USA. [John, Sinu P.; Feeley, Eric M.; Pertel, Thomas; Brass, Abraham L.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Charlestown, MA USA. [Smith, Sarah E.; Everitt, Aaron R.; Kellam, Paul] Wellcome Trust Sanger Inst, Hinxton, England. [Elia, Andrew E. H.; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Elia, Andrew E. H.; Elledge, Stephen J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Elia, Andrew E. H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Elledge, Stephen J.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Kellam, Paul] UCL, MRC UCL Ctr Med Mol Virol, Div Infect & Immun, London, England. RP Brass, AL (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01605 USA. EM abraham.brass@umassmed.edu RI Vora, Mehul/P-4848-2016; OI Vora, Mehul/0000-0002-1239-6458; Smith, Sarah/0000-0001-8699-7670 FU NIAID, NIH [1R01AI091786]; Wellcome Trust FX This work was generously supported by a grant (1R01AI091786) from the NIAID, NIH to A.L.B. A.L.B. is grateful to the Charles H. Hood Foundation, the Phillip T. and Susan M. Ragon Foundation, the Harvard and UMMS Centers for AIDS Research (CFARs) for their generous support. S.J.E. is an investigator with the Howard Hughes Medical Institute. P.K., S.E.S., and A.R.E are supported by the Wellcome Trust. NR 31 TC 49 Z9 55 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUL PY 2013 VL 87 IS 14 BP 7837 EP 7852 DI 10.1128/JVI.00481-13 PG 16 WC Virology SC Virology GA 172PX UT WOS:000321017700006 PM 23658454 ER PT J AU Gollub, RL Shoemaker, JM King, MD White, T Ehrlich, S Sponheim, SR Clark, VP Turner, JA Mueller, BA Magnotta, V O'Leary, D Ho, BC Brauns, S Manoach, DS Seidman, L Bustillo, JR Lauriello, J Bockholt, J Lim, KO Rosen, BR Schulz, SC Calhoun, VD Andreasen, NC AF Gollub, Randy L. Shoemaker, Jody M. King, Margaret D. White, Tonya Ehrlich, Stefan Sponheim, Scott R. Clark, Vincent P. Turner, Jessica A. Mueller, Bryon A. Magnotta, Vince O'Leary, Daniel Ho, Beng C. Brauns, Stefan Manoach, Dara S. Seidman, Larry Bustillo, Juan R. Lauriello, John Bockholt, Jeremy Lim, Kelvin O. Rosen, Bruce R. Schulz, S. Charles Calhoun, Vince D. Andreasen, Nancy C. TI The MCIC Collection: A Shared Repository of Multi-Modal, Multi-Site Brain Image Data from a Clinical Investigation of Schizophrenia SO NEUROINFORMATICS LA English DT Article DE Medical Image Data repository; Schizophrenia; fMRI; DWI; mMRI; Healthy controls ID INDEPENDENT COMPONENT ANALYSIS; AUDITORY ODDBALL TASK; DORSOLATERAL PREFRONTAL CORTEX; HIPPOCAMPAL VOLUME REDUCTION; 1ST EPISODE SCHIZOPHRENIA; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; CORTICAL THICKNESS; WORKING-MEMORY; BIPOLAR DISORDER AB Expertly collected, well-curated data sets consisting of comprehensive clinical characterization and raw structural, functional and diffusion-weighted DICOM images in schizophrenia patients and sex and age-matched controls are now accessible to the scientific community through an on-line data repository (coins.mrn.org). The Mental Illness and Neuroscience Discovery Institute, now the Mind Research Network (MRN, http://www.mrn.org/), comprised of investigators at the University of New Mexico, the University of Minnesota, Massachusetts General Hospital, and the University of Iowa, conducted a cross-sectional study to identify quantitative neuroimaging biomarkers of schizophrenia. Data acquisition across multiple sites permitted the integration and cross-validation of clinical, cognitive, morphometric, and functional neuroimaging results gathered from unique samples of schizophrenia patients and controls using a common protocol across sites. Particular effort was made to recruit patients early in the course of their illness, at the onset of their symptoms. There is a relatively even sampling of illness duration in chronic patients. This data repository will be useful to 1) scientists who can study schizophrenia by further analysis of this cohort and/or by pooling with other data; 2) computer scientists and software algorithm developers for testing and validating novel registration, segmentation, and other analysis software; and 3) educators in the fields of neuroimaging, medical image analysis and medical imaging informatics who need exemplar data sets for courses and workshops. Sharing provides the opportunity for independent replication of already published results from this data set and novel exploration. This manuscript describes the inclusion/exclusion criteria, imaging parameters and other information that will assist those wishing to use this data repository. C1 [Gollub, Randy L.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Gollub, Randy L.; Manoach, Dara S.; Rosen, Bruce R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Shoemaker, Jody M.; King, Margaret D.; Clark, Vincent P.; Turner, Jessica A.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [White, Tonya] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [White, Tonya] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Ehrlich, Stefan; Brauns, Stefan] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Dresden, Germany. [Sponheim, Scott R.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Sponheim, Scott R.; Mueller, Bryon A.; Lim, Kelvin O.; Schulz, S. Charles] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Magnotta, Vince] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [O'Leary, Daniel; Ho, Beng C.; Bockholt, Jeremy; Andreasen, Nancy C.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Clark, Vincent P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Lauriello, John] Univ Missouri, Dept Psychiat, Columbia, MO 65201 USA. [Bockholt, Jeremy] Adv Biomed Informat Grp LLC, Iowa City, IA USA. [Bustillo, Juan R.; Calhoun, Vince D.] Univ New Mexico, Dept Psychiat, Albuquerque, MN USA. [Seidman, Larry] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Brauns, Stefan] Charite, Dept Psychiat, D-13353 Berlin, Germany. RP Gollub, RL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 120,Suite 101D, Charlestown, MA 02129 USA. EM RGOLLUB@PARTNERS.ORG RI Clark, Vincent/B-3343-2010; bustillo, juan/J-7067-2013; Ho, Beng-Choon/D-6959-2011; Turner, Jessica/H-7282-2015 OI Clark, Vincent/0000-0002-9151-2102; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044; Ho, Beng-Choon/0000-0003-3976-1555; Turner, Jessica/0000-0003-0076-8434 FU Department of Energy through Mind Research Network (MRN) [DE-FG02-99ER62764]; Department of Energy National Association for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award; Blowitz-Ridgeway Foundation; Essel Foundation; NWO ZonMw TOP [91211021]; DFG; Mind Research Network, National Institutes of Health through NCRR [RR001066]; NIMH [K08 MH068540, RR021992]; NCRR [P41 RR14075, M01 RR 01066]; NIBIB [R01EB006841, R01EB005846, 2R01 EB000840, 1RC1MH089257]; [U24 RR021992] FX This work was supported primarily by the Department of Energy DE-FG02-99ER62764 through its support of the Mind Research Network (MRN, formerly known as the MIND Institute) and the consortium as well as by the National Association for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award (to SE) as well as through the Blowitz-Ridgeway and Essel Foundations, and through NWO ZonMw TOP 91211021, the DFG research fellowship (to SE), the Mind Research Network, National Institutes of Health through NCRR 5 month-RR001066 (MGH General Clinical Research Center), NIMH K08 MH068540, the RR021992 Informatics Research Network with NCRR Supplements to P41 RR14075 (MGH), M01 RR 01066 (MGH), NIBIB R01EB006841 (MRN), R01EB005846 (MRN), 2R01 EB000840 (MRN), 1RC1MH089257 (MRN), as well as grant U24 RR021992. NR 124 TC 30 Z9 30 U1 3 U2 22 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD JUL PY 2013 VL 11 IS 3 BP 367 EP 388 DI 10.1007/s12021-013-9184-3 PG 22 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 189HY UT WOS:000322259300008 PM 23760817 ER PT J AU Liu, S Wang, J Su, YJ Guerrero, C Zeng, YX Mitra, D Brooks, PJ Fisher, DE Song, HJ Wang, YS AF Liu, Shuo Wang, Jin Su, Yijing Guerrero, Candace Zeng, Yaxue Mitra, Devarati Brooks, Philip J. Fisher, David E. Song, Hongjun Wang, Yinsheng TI Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CROSS-LINK LESION; THYMINE DNA; MAMMALIAN DNA; DEMETHYLATION; 5-HYDROXYMETHYLCYTOSINE; GLYCOSYLASE; 5-CARBOXYLCYTOSINE; PROTEIN; BASE AB Recent studies showed that Ten-eleven translocation (Tet) family dioxygenases can oxidize 5-methyl-2'-deoxycytidine (5-mdC) in DNA to yield the 5-hydroxymethyl, 5-formyl and 5-carboxyl derivatives of 2'-deoxycytidine (5-HmdC, 5-FodC and 5-CadC). 5-HmdC in DNA may be enzymatically deaminated to yield 5-hydroxymethyl-2'-deoxyuridine (5-HmdU). After their formation at CpG dinucleotide sites, these oxidized pyrimidine nucleosides, particularly 5-FodC, 5-CadC, and 5-HmdU, may be cleaved from DNA by thymine DNA glycosylase, and subsequent action of base-excision repair machinery restores unmethylated cytosine. These processes are proposed to be important in active DNA cytosine demethylation in mammals. Here we used a reversed-phase HPLC coupled with tandem mass spectrometry (LC-MS/MS/MS) method, along with the use of stable isotope-labeled standards, for accurate measurements of 5-HmdC, 5-FodC, 5-CadC and 5-HmdU in genomic DNA of cultured human cells and multiple mammalian tissues. We found that overexpression of the catalytic domain of human Tet1 led to marked increases in the levels of 5-HmdC, 5-FodC and 5-CadC, but only a modest increase in 5-HmdU, in genomic DNA of HEK293T cells. Moreover, 5-HmdC is present at a level that is approximately 2-3 and 3-4 orders of magnitude greater than 5-FodC and 5-CadC, respectively, and 35-400 times greater than 5-HmdU in the mouse brain and skin, and human brain. The robust analytical method built a solid foundation for dissecting the molecular mechanisms of active cytosine demethylation, for measuring these 5-mdC derivatives and assessing their involvement in epigenetic regulation in other organisms and for examining whether these 5-mdC derivatives can be used as biomarkers for human diseases. C1 [Liu, Shuo; Wang, Yinsheng] Univ Calif Riverside, Environm Toxicol Grad Program, Riverside, CA 92521 USA. [Wang, Jin; Guerrero, Candace; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Su, Yijing; Zeng, Yaxue; Song, Hongjun] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. [Su, Yijing; Zeng, Yaxue; Song, Hongjun] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Su, Yijing; Zeng, Yaxue; Song, Hongjun] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Mitra, Devarati; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Brooks, Philip J.] NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. [Brooks, Philip J.] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. [Brooks, Philip J.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP Wang, YS (reprint author), Univ Calif Riverside, Environm Toxicol Grad Program, Riverside, CA 92521 USA. EM yinsheng.wang@ucr.edu FU National Institutes of Health (NIH) [DK082779, NS047344, ES021957, AR043369]; Maryland Stem Cell Research Fund postdoctoral fellowship; NIH [DK082779] FX National Institutes of Health (NIH) [DK082779 to Y.W., NS047344 and ES021957 to H. S. and AR043369 to D. E. F.]; Maryland Stem Cell Research Fund postdoctoral fellowship (to Y.S and Y.Z). Funding for open access charge: NIH [DK082779]. NR 34 TC 53 Z9 53 U1 3 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2013 VL 41 IS 13 BP 6421 EP 6429 DI 10.1093/nar/gkt360 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BK UT WOS:000322458800014 PM 23658232 ER PT J AU Gitlin, SA Wright, DL AF Gitlin, Susan A. Wright, Diane L. TI Susan E. Lanzendorf (1958-2013): innovator, mentor, colleague OBITUARY SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Biographical-Item C1 [Gitlin, Susan A.] Eastern Virginia Med Sch, Jones Inst Reprod Med, Dept Obstet & Gynecol, Norfolk, VA 23501 USA. [Wright, Diane L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fertil Ctr Vincent Obstet & Gynecol, Boston, MA USA. RP Gitlin, SA (reprint author), Eastern Virginia Med Sch, Jones Inst Reprod Med, Dept Obstet & Gynecol, Norfolk, VA 23501 USA. EM GitlinSA@EVMS.EDU NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1472-6483 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD JUL PY 2013 VL 27 IS 1 BP 31 EP 32 DI 10.1016/j.rbmo.2013.05.002 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 182LJ UT WOS:000321743800010 ER PT J AU Nedjat-Haiem, FR Carrion, IV Cribbs, K Lorenz, K AF Nedjat-Haiem, Frances R. Carrion, Iraida V. Cribbs, Kristen Lorenz, Karl TI Advocacy at the End of Life: Meeting the Needs of Vulnerable Latino Patients SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE Latinos; advocacy; end of life; public sector health care system ID ADVANCED CANCER; HEALTH-CARE; SOCIAL-WORK AB This research explores health care professionals' understanding of the problems that arise in managing a terminal condition impacting the Latino population and conceptualizes the components of patient advocacy that address gaps in end-of-life care for patients and their family members. Limited research exists regarding patient advocacy from the perspectives of health care providers working with vulnerable Latino populations utilizing a public sector health care system. Forty-six semi-structured interviews were conducted with providers from different disciplines including medicine, nursing, social work, and chaplaincy. Although roles and responsibilities vary among health providers, it is imperative that all providers become aware of the need for patient advocacy. Doing so is not only in the best interest of vulnerable Latino populations but also has overarching financial benefits and positive outcomes for patients, administrators, and public health care systems. Social workers are the ideal professionals to assume leadership roles and share their knowledge of how to advocate effectively for the most vulnerable populations. C1 [Nedjat-Haiem, Frances R.; Lorenz, Karl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Carrion, Iraida V.] Univ S Florida, Sch Social Work, Tampa, FL USA. [Cribbs, Kristen] Columbia Univ, Sch Publ Hlth, New York, NY USA. RP Nedjat-Haiem, FR (reprint author), VA Greater Los Angeles Healthcare Syst, VA Associated Hlth Postdoctoral Fellowship Progra, Off Acad Affiliat, HSR&D Ctr Excellence, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM nedjatha@gmail.com RI chen, zhu/K-5923-2013; OI Carrion, Iraida/0000-0003-4076-6644 NR 45 TC 3 Z9 3 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PD JUL 1 PY 2013 VL 52 IS 6 BP 558 EP 577 DI 10.1080/00981389.2013.779359 PG 20 WC Social Work SC Social Work GA 185RA UT WOS:000321986600004 PM 23865972 ER PT J AU Balevich, EC Wein, ND Flory, JD AF Balevich, Emily C. Wein, Naftali D. Flory, Janine D. TI Cigarette Smoking and Measures of Impulsivity in a College Sample SO SUBSTANCE ABUSE LA English DT Article DE Delay discounting; disinhibition; impulsivity; reward seeking; tobacco use ID IOWA GAMBLING TASK; DECISION-MAKING; FUTURE CONSEQUENCES; NICOTINE DEPENDENCE; DRUG-USE; SMOKERS; DELAY; NONSMOKERS; DISORDERS; BEHAVIOR AB .Background: An association between impulsivity and smoking has been consistently reported in the literature, but few studies have examined how distinct dimensions of impulsivity may relate differentially to smoking initiation versus persistent smoking. The aim of the current study was to examine the relationship between self-report and behavioral measures of impulsivity and smoking status in college students. Methods: Participants (N = 243) completed a self-report history of tobacco use, 2 self-report measures of impulsivity (the Barratt Impulsiveness Scale and Zuckerman Sensation-Seeking Scale), and 2 behavioral measures (the Delay Discounting Task and Iowa Gambling Task). All participants were classified as never-smokers, triers, or smokers based on their smoking history, and between-group differences on the 4 measures were examined. Results: On the self-report measures, all 3 groups differed on sensation seeking, with the never-smokers reporting the lowest levels and the smokers reporting the highest. Furthermore, the smokers reported significantly higher disinhibitory impulsivity than the triers and never-smokers. The groups did not differ on the behavioral measures. Conclusions: These results indicate that distinct dimensions of impulsivity characterize different smoking phenotypes. In particular, sensation seeking is associated with the initiation of smoking, whereas disinhibitory impulsivity is associated with the transition to more persistent and regular use of cigarettes. C1 [Balevich, Emily C.; Wein, Naftali D.] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Balevich, Emily C.] CUNY, Grad Ctr, Flushing, NY USA. [Flory, Janine D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Flory, Janine D.] James J Peters Bronx VA Med Ctr, Bronx, NY USA. RP Balevich, EC (reprint author), CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. EM emily.balevich@qc.cuny.edu FU National Institutes of Health [MH K01-069979] FX This research was supported by National Institutes of Health grant MH K01-069979 (J.D.F.). NR 40 TC 9 Z9 9 U1 4 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PD JUL 1 PY 2013 VL 34 IS 3 BP 256 EP 262 DI 10.1080/08897077.2012.763082 PG 7 WC Substance Abuse SC Substance Abuse GA 181SF UT WOS:000321688100005 PM 23844956 ER PT J AU Gerits, A Vanduffel, W AF Gerits, Annelies Vanduffel, Wim TI Optogenetics in primates: a shining future? SO TRENDS IN GENETICS LA English DT Review DE optogenetics; nonhuman primates; behavior; bioengineered opsins ID FRONTAL EYE FIELD; CENTRAL SEROTONERGIC NEURONS; OPTICAL NEURAL-CONTROL; IN-VIVO; HALOBACTERIUM-HALOBIUM; ADENOASSOCIATED VIRUS; MILLISECOND-TIMESCALE; FLUORESCENT PROTEINS; LENTIVIRAL VECTORS; CONDITIONED FEAR AB To understand the functional role of specific neurons in micro- and macro-brain circuitry, health, and disease, it is critical to control their activity precisely. This ambitious goal was first achieved by optogenetics, allowing researchers to increase or decrease neural activity artificially with high temporal and spatial precision. In contrast to the revolution optogenetics engendered in invertebrate and rodent research, only a few studies have reported optogenetic-induced neuronal and behavioral effects in primates. Such studies are nonetheless critical before optogenetics can be applied in a clinical setting. Here, we review the state-of-the-art tools for performing optogenetics in mammals, emphasizing recent neuronal and behavioral results obtained in nonhuman primates. C1 [Gerits, Annelies; Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Vanduffel, W (reprint author), Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, Campus Gasthuisberg, B-3000 Louvain, Belgium. EM Wim@nmr.mgh.harvard.edu FU IWT-SBO [110068]; Geconcerteerde Onderzoeks Actie [10/19]; Inter-University Attraction Pole [7/11]; Pogramme Financing [PF/10/008]; FWO [G0622.08.N10, G0831.11.N10] FX We thank S. Raiguel, P. Vancraeyenest, and K. Nelissen for their help and comments. G.A. and W.V. received support from IWT-SBO 110068, Geconcerteerde Onderzoeks Actie 10/19, Inter-University Attraction Pole 7/11, Pogramme Financing PF/10/008, and FWO grants G0622.08.N10 and G0831.11.N10. NR 102 TC 24 Z9 24 U1 3 U2 47 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2013 VL 29 IS 7 BP 403 EP 411 DI 10.1016/j.tig.2013.03.004 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 191NK UT WOS:000322419600005 PM 23623742 ER PT J AU McCallum, JC Limmer, KK Perricone, A Bandyk, D Kansal, N AF McCallum, John C. Limmer, Karl K. Perricone, Anthony Bandyk, Dennis Kansal, Nikhil TI Case report and review of the literatureTotal Endovascular Repair of Acute Ascending Aortic Rupture: A Case Report and Review of the Literature SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE thoracic aorta rupture; ascending aorta; endovascular repair; TEVAR ID STENT-GRAFT PLACEMENT; A DISSECTION; MANAGEMENT AB Thoracic aortic endografting has been successfully implemented to treat aneurysmal disease of the distal aortic arch and descending thoracic aorta. Although there are reports of ascending aortic endovascular interventions, the total endovascular repair of a ruptured ascending aorta secondary to a Type A dissection has not been described. We report the case of a 77-year-old patient who presented with a ruptured ascending aortic aneurysm secondary to degeneration of a Stanford type A aortic dissection. His surgical history was significant for orthotropic heart transplant 19 years prior. The dissection, aneurysm, and rupture occurred in the native aorta distal to the ascending aortic suture line. At presentation, he was hemodynamically unstable with a right hemothorax. We placed 3 Medtronic Talent Thoracic Stent Graft devices (Medtronic Inc, Minneapolis, MN) across the suture line in the ascending aorta, excluding the rupture. The patient survived and has been followed to 25 months. C1 [McCallum, John C.; Bandyk, Dennis; Kansal, Nikhil] Univ Calif San Diego, Dept Surg, Div Vasc Surg, San Diego, CA 92103 USA. [Limmer, Karl K.] Massachusetts Gen Hosp, Dept Surg, Div Cardiothorac Surg, Boston, MA 02114 USA. [Perricone, Anthony] Univ Calif San Diego, Dept Surg, Div Cardiothorac Surg, San Diego, CA 92103 USA. RP Kansal, N (reprint author), Univ Calif San Diego, Dept Surg, 200 W Arbor Dr, San Diego, CA 92103 USA. EM nkansal@ucsd.edu NR 14 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD JUL PY 2013 VL 47 IS 5 BP 374 EP 378 DI 10.1177/1538574413486838 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 185OS UT WOS:000321979600009 PM 23697343 ER PT J AU Yallampalli, S Irani, Z Kalva, SP AF Yallampalli, Sasidhar Irani, Zubin Kalva, Sanjeeva P. TI Endovascular Removal of a Permanent "TrapEase" Inferior Vena Cava Filter SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE IVC filter; TrapEase; filter retrieval ID PULMONARY-EMBOLISM; EXPERIENCE AB Inferior vena cava (IVC) filter placement has seen a rising trend over the past decade. Although effective in the prevention of future pulmonary emboli, filters are associated with several long-term complications including deep venous thrombosis, filter migration, filter fracture, and caval thrombosis. The IVC filters have evolved over the years to minimize these unwarranted sequelae. We describe a technique to remove a permanent IVC filter in a patient who no longer required mechanical protection. C1 [Yallampalli, Sasidhar; Irani, Zubin; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Yallampalli, S (reprint author), 55 Fruit St,Gray 2, Boston, MA 02114 USA. EM syallampalli@partners.org NR 11 TC 5 Z9 5 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD JUL PY 2013 VL 47 IS 5 BP 379 EP 382 DI 10.1177/1538574413487437 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 185OS UT WOS:000321979600010 PM 23645394 ER PT J AU Wang, ML Peterson, KE Richmond, TK Spadano-Gasbarro, J Greaney, ML Mezgebu, S McCormick, M Austin, SB AF Wang, Monica L. Peterson, Karen E. Richmond, Tracy K. Spadano-Gasbarro, Jennifer Greaney, Mary L. Mezgebu, Solomon McCormick, Marie Austin, S. Bryn TI Family Physical Activity and Meal Practices Associated With Disordered Weight Control Behaviors in a Multiethnic Sample of Middle-School Youth SO ACADEMIC PEDIATRICS LA English DT Article DE disordered weight control; family; meals; physical activity; youth ID BODY-MASS INDEX; EATING-DISORDERS; DIETARY-INTAKE; LONGITUDINAL FINDINGS; MULTIPLE IMPUTATION; PARENTAL INFLUENCES; ADOLESCENT GIRLS; PROJECT EAT; OVERWEIGHT; RISK AB OBJECTIVE: Family practices around weight-related behaviors can shape children's development of disordered weight control behaviors (DWCB), such as vomiting, taking laxatives, or taking diet pills without a prescription. This study examined family meal and physical activity (PA) practices associated with DWCB among a multiethnic sample of youth. METHODS: We assessed self-report data on frequency of family sit-down dinners, types of parental involvement in their children's PA, and DWCB are from 15,461 6th to 8th grade girls and boys in 47 middle schools participating in the Massachusetts Healthy Choices Study at baseline (2005). RESULTS: Youth who had family sit-down dinners every day had lower odds of DWCB (girls: odds ratio [OR] 0.3; 95% confidence interval [CI] 0.2-0.5; boys: OR 0.6; 95% CI 0.4-0.9) than youth who never had family sit-down dinners. Similar effect estimates were found for youth who had family sit-down dinners most days. Parental provision of rides to and from a PA event was also found to be protective against DWCB among girls (OR 0.7; 95% Cl 0.5-0.9). In contrast, parental participation in PA with their children was associated with increased risk for DWCB (girls: OR 1.4; 95% CI 1.0-1.8; boys: OR 1.9; 95% CI 1.4-2.4). These associations did not differ by race/ethnicity or weight status. CONCLUSIONS: Programs emphasizing the importance of family meals may be beneficial in preventing DWCB in youth of all ethnicities. Further research is needed on how various methods of parental involvement in their children's PA are associated with DWCB. C1 [Wang, Monica L.] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. [Wang, Monica L.; McCormick, Marie; Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Spadano-Gasbarro, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Human Nutr Program, Ann Arbor, MI 48109 USA. [Richmond, Tracy K.; Austin, S. Bryn] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Mezgebu, Solomon] Massachusetts Dept Publ Hlth, Boston, MA USA. RP Wang, ML (reprint author), Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. EM Monica.Wang@umassmed.edu OI McCormmick, Marie/0000-0002-3938-1707 FU Ellen Feldberg Gordon Fund for Eating Disorders Research; Strategic Training Initiative for the Prevention of Eating Disorders Dissertation Award; Massachusetts Department of Public Health; International Nutrition Foundation Inc.; Centers for Disease Control and Prevention [U58/CCU 12282]; Leadership Education in Adolescent Health project, Maternal and Child Health Bureau, HRSA [6T71-MC00009] FX The authors thank Sylvia Stevens-Edouard, Vanessa Cavallero, Vivian Morris, Christine Horan, Maria Bettencourt, and Christine Nordstrom for their contributions to the Healthy Choices study and school staff and students who participated in the study. This research was supported by the Ellen Feldberg Gordon Fund for Eating Disorders Research, the Strategic Training Initiative for the Prevention of Eating Disorders Dissertation Award, and the Massachusetts Department of Public Health in collaboration with the International Nutrition Foundation Inc. Partial funding for this project was also provided by Cooperative Agreement U58/CCU 12282 with the Centers for Disease Control and Prevention. S. Bryn Austin is supported by the Leadership Education in Adolescent Health project, Maternal and Child Health Bureau, HRSA grant 6T71-MC00009. NR 49 TC 4 Z9 4 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD JUL-AUG PY 2013 VL 13 IS 4 BP 379 EP 385 PG 7 WC Pediatrics SC Pediatrics GA 186QG UT WOS:000322058600015 PM 23830023 ER PT J AU Weiner, MW Friedl, KE Pacifico, A Chapman, JC Jaffee, MS Little, DM Manley, GT McKee, A Petersen, RC Pitman, RK Yaffe, K Zetterberg, H Obana, R Bain, LJ Carrillo, MC AF Weiner, Michael W. Friedl, Karl E. Pacifico, Anthony Chapman, Julie C. Jaffee, Michael S. Little, Deborah M. Manley, Geoffrey T. McKee, Ann Petersen, Ronald C. Pitman, Roger K. Yaffe, Kristine Zetterberg, Henrik Obana, Robert Bain, Lisa J. Carrillo, Maria C. TI Military risk factors for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Risk factors; Military medicine; Traumatic brain injury; Posttraumatie stress disorder; Tau; Beta-amyloid; Apolipoprotein E e4; Biomarkers; Alzheimer's Disease Neuroimaging Initiative; Vietnam; Veterans; Chronic traumatic encephalopathy; Blast injury ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; POSTCONCUSSIVE SYMPTOMS; COGNITIVE RESERVE; HEAD-INJURY; BLAST; ENCEPHALOPATHY; HEALTH; CARE; AFGHANISTAN AB Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Weiner, Michael W.; Yaffe, Kristine] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Weiner, Michael W.; Manley, Geoffrey T.; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Friedl, Karl E.; Pacifico, Anthony] US Army Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA. [Chapman, Julie C.] Vet Affairs Med Ctr, War Related Illness & Injury Study Ctr, Washington, DC 20422 USA. [Chapman, Julie C.] Georgetown Univ, Sch Med, Washington, DC USA. [Jaffee, Michael S.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Little, Deborah M.] Texas A&M Hlth Sci Coll Med, College Stn, TX USA. [McKee, Ann] Boston Univ, Sch Med, New England Vet Healthcare Syst, Boston, MA 02118 USA. [McKee, Ann] Boston Univ, Sch Med, Brain Banks, Boston, MA 02118 USA. [McKee, Ann] Ctr Study Traumat Encephalopathy, Boston, MA USA. [Petersen, Ronald C.] Mayo Clin, Rochester, MN USA. [Pitman, Roger K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zetterberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Obana, Robert] Vet Hlth Res Inst, Northern Calif Inst Res & Educ, San Francisco, CA USA. [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. RP Carrillo, MC (reprint author), Alzheimers Assoc, Chicago, IL USA. EM Maria.Carrillo@alz.org RI Saykin, Andrew/A-1318-2007; Schmidt, Mark/I-5052-2016; Jack, Clifford/F-2508-2010; OI Saykin, Andrew/0000-0002-1376-8532; Schmidt, Mark/0000-0003-3417-8977; Jack, Clifford/0000-0001-7916-622X; Friedl, Karl/0000-0002-3134-8427 NR 48 TC 38 Z9 38 U1 6 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2013 VL 9 IS 4 BP 445 EP 451 DI 10.1016/j.jalz.2013.03.005 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 182GF UT WOS:000321729000013 PM 23809365 ER PT J AU Crutch, SJ Schott, JM Rabinovici, GD Boeve, BF Cappa, SF Dickerson, BC Dubois, B Graff-Radford, NR Krolak-Salmon, P Lehmann, M Mendez, MF Pijnenburg, Y Ryan, NS Scheltens, P Shakespeare, T Tang-Wai, DF van der Flier, WM Bain, L Carrillo, MC Fox, NC AF Crutch, Sebastian J. Schott, Jonathan M. Rabinovici, Gil D. Boeve, Bradley F. Cappa, Stefano F. Dickerson, Bradford C. Dubois, Bruno Graff-Radford, Neill R. Krolak-Salmon, Pierre Lehmann, Manja Mendez, Mario F. Pijnenburg, Yolande Ryan, Natalie S. Scheltens, Philip Shakespeare, Tim Tang-Wai, David F. van der Flier, Wiesje M. Bain, Lisa Carrillo, Maria C. Fox, Nick C. TI Shining a light on posterior cortical atrophy SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's dementia; Posterior cortical atrophy; Atypical dementia; Simultanagnosia; Visual disturbances; Differential diagnosis; Diagnostic criteria; Visualperceptual disturbances ID ALZHEIMERS-DISEASE; METABOLIC DEFICITS; THICKNESS; AD AB Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Crutch, Sebastian J.; Schott, Jonathan M.; Lehmann, Manja; Ryan, Natalie S.; Shakespeare, Tim; Fox, Nick C.] UCL Inst Neurol, Dementia Res Ctr, London, England. [Rabinovici, Gil D.; Lehmann, Manja] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Boeve, Bradley F.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Cappa, Stefano F.] Univ Vita Salute San Raffaele, Ctr Cognit Neurosci, Milan, Italy. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Dubois, Bruno] Univ Paris 06, Salpetriere Hosp, Inst Memory & Alzheimers Dis, UMR S975, Paris, France. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Krolak-Salmon, Pierre] Univ Lyon, Hosp Civils Lyon, CNRS, Lyon Memory Ctr,INSERM U1028,UMR5292, Lyon, France. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Pijnenburg, Yolande; Scheltens, Philip; van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Pijnenburg, Yolande; Scheltens, Philip; van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. [Tang-Wai, David F.] Univ Toronto, Univ Hlth Network Memory Clin, Div Neurol, Toronto, ON, Canada. [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. RP Carrillo, MC (reprint author), Alzheimers Assoc, Chicago, IL USA. EM maria.carrillo@alz.org RI Schott, Jonathan/A-9065-2011; Lehmann, Manja/B-9717-2014; Fox, Nick/B-1319-2009; OI Schott, Jonathan/0000-0003-2059-024X; Fox, Nick/0000-0002-6660-657X; Shakespeare, Timothy/0000-0002-2155-4948 FU Alzheimer's Society [108]; Medical Research Council [G0900421] NR 22 TC 20 Z9 23 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2013 VL 9 IS 4 BP 463 EP 465 DI 10.1016/j.jalz.2012.11.004 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 182GF UT WOS:000321729000016 PM 23274153 ER PT J AU Koulajian, K Ivovic, A Ye, KT Desai, T Shah, A Fantus, IG Ran, QT Giacca, A AF Koulajian, Khajag Ivovic, Alexander Ye, Kaitai Desai, Tejas Shah, Anu Fantus, I. George Ran, Qitao Giacca, Adria TI Overexpression of glutathione peroxidase 4 prevents beta-cell dysfunction induced by prolonged elevation of lipids in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE oxidative stress; lipid peroxide; glutathione peroxidase 4; lipotoxicity; beta-cell dysfunction; in vivo ID FREE FATTY-ACIDS; STIMULATED INSULIN-SECRETION; ENZYME GENE-EXPRESSION; RAT PANCREATIC-ISLETS; KAPPA-B ACTIVATION; OXIDATIVE STRESS; NONDIABETIC MEN; SUPEROXIDE-DISMUTASE; NADPH OXIDASE; GLUCOSE AB We have shown that oxidative stress is a mechanism of free fatty acid (FFA)-induced beta-cell dysfunction. Unsaturated fatty acids in membranes, including plasma and mitochondrial membranes, are substrates for lipid peroxidation, and lipid peroxidation products are known to cause impaired insulin secretion. Therefore, we hypothesized that mice overexpressing glutathione peroxidase-4 (GPx4), an enzyme that specifically reduces lipid peroxides, are protected from fat-induced beta-cell dysfunction. GPx4-overexpressing mice and their wild-type littermate controls were infused intravenously with saline or oleate for 48 h, after which reactive oxygen species (ROS) were imaged, using dihydrodichlorofluorescein diacetate in isolated islets, and beta-cell function was assessed ex vivo in isolated islets and in vivo during hyperglycemic clamps. Forty-eight-hour FFA elevation in wild-type mice increased ROS and the lipid peroxidation product malondialdehyde and impaired beta-cell function ex vivo in isolated islets and in vivo, as assessed by decreased disposition index. Also, islets of wild-type mice exposed to oleate for 48 h had increased ROS and lipid peroxides and decreased beta-cell function. In contrast, GPx4-overexpressing mice showed no FFA-induced increase in ROS and lipid peroxidation and were protected from the FFA-induced impairment of beta-cell function assessed in vitro, ex vivo and in vivo. These results implicate lipid peroxidation in FFA-induced beta-cell dysfunction. C1 [Koulajian, Khajag; Ivovic, Alexander; Ye, Kaitai; Desai, Tejas; Shah, Anu; Fantus, I. George; Giacca, Adria] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON M5S 1A8, Canada. [Shah, Anu; Fantus, I. George] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Shah, Anu; Fantus, I. George] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada. [Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Ran, Qitao] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Fantus, I. George; Giacca, Adria] Univ Toronto, Fac Med, Dept Med, Toronto, ON, Canada. [Fantus, I. George; Giacca, Adria] Univ Toronto, Banting & Best Diabet Ctr, Toronto, ON M5G 1L5, Canada. [Fantus, I. George; Giacca, Adria] Univ Toronto, Inst Med Sci, Fac Med, Toronto, ON, Canada. RP Giacca, A (reprint author), Univ Toronto, 1 Kings Coll Circle,Med Sci Bldg,Rm 3336, Toronto, ON, Canada. EM adria.giacca@utoronto.ca FU Canadian Institutes of Health Research [MOP-69018]; Banting and Best Diabetes Centre (University of Toronto); Ontario Graduate Scholarship; Ontario Graduate Scholarship for Science and Technology FX This work was supported by Canadian Institutes of Health Research Grants MOP-69018 (A. Giacca). K. Koulajian was supported by Scholarships from the Banting and Best Diabetes Centre (University of Toronto), an Ontario Graduate Scholarship, and an Ontario Graduate Scholarship for Science and Technology. NR 72 TC 7 Z9 7 U1 0 U2 7 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 JUL PY 2013 VL 305 IS 2 BP E254 EP E262 DI 10.1152/ajpendo.00481.2012 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 184OS UT WOS:000321902000009 PM 23695217 ER PT J AU Vargas, LA Diaz, RG Swenson, ER Perez, NG Alvarez, BV AF Vargas, Lorena A. Diaz, Romina G. Swenson, Erik R. Perez, Nestor G. Alvarez, Bernardo V. TI Inhibition of carbonic anhydrase prevents the Na+/H+ exchanger 1-dependent slow force response to rat myocardial stretch SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE NHE1 Na+/H+ exchanger; carbonic anhydrase II; papillary muscle; slow force response; cardiac hypertrophy ID INDUCED CARDIOMYOCYTE HYPERTROPHY; MYOCYTES IN-VITRO; CARDIAC-HYPERTROPHY; HEART-FAILURE; ANGIOTENSIN-II; H+ EXCHANGE; MEDIATED REGULATION; MECHANICAL STRETCH; PAPILLARY-MUSCLE; GENE-EXPRESSION AB Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca2+ transient that follows the NHE1 Na+/H+ exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pH(i)) were evaluated in rat papillary muscle bathed with CO2/HCO3- buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 mu M). SFR control was 120 +/- 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 +/- 4%, n = 6). The SFR corresponded to a maximal increase in pH(i) of 0.18 +/- 0.02 pH units (n = 4), and pH(i) changes were blocked by ETZ (0.04 +/- 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 +/- 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90(RSK) kinase inhibitor SL0101-1 (10 mu M) blocked the SFR of heart muscles after stretch 102 +/- 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H+ transport in the myocardium. C1 [Vargas, Lorena A.; Diaz, Romina G.; Perez, Nestor G.; Alvarez, Bernardo V.] Univ Nacl La Plata, Fac Ciencias Med, Consejo Nacl Invest Cient & Tecn, Ctr Invest Cardiovasc, RA-1900 La Plata, Buenos Aires, Argentina. [Swenson, Erik R.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Alvarez, BV (reprint author), Univ Nacl La Plata, Fac Ciencias Med, Consejo Nacl Invest Cient & Tecn, Ctr Invest Cardiovasc, RA-1900 La Plata, Buenos Aires, Argentina. EM balvarez@med.unlp.edu.ar FU Agencia Nacional de Promocion Cientifica Grant (PICT) [01011, 320/08] FX This work was supported by the Agencia Nacional de Promocion Cientifica Grant (PICT 2007 No. 01011, Res. No. 320/08) to B. V. Alvarez. B. V. Alvarez and N. G. Perez are Established Investigators of the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET, Argentina). L. A. Vargas and R. G. Diaz are Fellows of CONICET. NR 61 TC 5 Z9 5 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2013 VL 305 IS 2 BP H228 EP H237 DI 10.1152/ajpheart.00055.2013 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 184PD UT WOS:000321903500010 PM 23709596 ER PT J AU Hedgire, SS McDermott, S Borczuk, D Elmi, A Saini, S Harisinghani, MG AF Hedgire, Sandeep S. McDermott, Shaunagh Borczuk, David Elmi, Azadeh Saini, Sanjay Harisinghani, Mukesh G. TI The Spectrum of IgG4-Related Disease in the Abdomen and Pelvis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE autoimmune pancreatitis; IgG4-related disease; IgG4-related sclerosing cholangitis; retroperitoneal fibrosis ID HEPATIC INFLAMMATORY PSEUDOTUMOR; IGG4-POSITIVE PLASMA-CELLS; ABDOMINAL AORTIC-ANEURYSM; AUTOIMMUNE PANCREATITIS; SCLEROSING DISEASE; CLINICOPATHOLOGICAL-ENTITY; IMAGING FINDINGS; RETROPERITONEAL FIBROSIS; SYSTEMIC-DISEASE; DIFFERENTIATION AB OBJECTIVE. IgG4-related disease was not recognized as a specific clinical entity until 2003 when extrapancreatic lesions were reported in patients with autoimmune pancreatitis. IgG4-related disease is characterized by elevated serum IgG4 levels and infiltration of the target organ by IgG4-positive plasma cells. The complete gamut of visceral involvement is still being outlined. The purpose of this article is to highlight the plethora of lesions under the spectrum of IgG4-related disease of the abdomen and pelvis, describe their imaging appearances on multimodality cross-sectional imaging, and discuss the differential diagnoses. CONCLUSION. It is important for radiologists to recognize the multiorgan involvement and few classic features of IgG4-related disease that often tend to simulate malignancy. C1 [Hedgire, Sandeep S.; McDermott, Shaunagh; Borczuk, David; Elmi, Azadeh; Saini, Sanjay; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Hedgire, SS (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM Hedgire.Sandeep@mgh.harvard.edu NR 46 TC 9 Z9 10 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2013 VL 201 IS 1 BP 14 EP 22 DI 10.2214/AJR.12.9995 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900028 PM 23789654 ER PT J AU Hara, AK Wellnitz, CV Paden, RG Pavlicek, W Sahani, DV AF Hara, Amy K. Wellnitz, Clinton V. Paden, Robert G. Pavlicek, William Sahani, Dushyant V. TI Reducing Body CT Radiation Dose: Beyond Just Changing the Numbers SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT; radiation dose ID STATISTICAL ITERATIVE RECONSTRUCTION; FILTERED BACK-PROJECTION; ABDOMINAL CT; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; CROHN DISEASE; TUBE VOLTAGE; REDUCTION; SELECTION; NOISE AB OBJECTIVE. CT dose reduction has become a top priority for many radiology practices as a result of federal and state initiatives and public concern. Implementing this in practice, however, is difficult because of the variability between practices, CT scanners, radiologist preferences, and institutional capacity. CONCLUSION. This article will discuss strategies for successful CT dose reduction instituted in multivendor practices. C1 [Hara, Amy K.; Wellnitz, Clinton V.; Paden, Robert G.; Pavlicek, William] Mayo Clin Arizona, Dept Diagnost Radiol, Scottsdale, AZ 85259 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Diagnost Radiol, Boston, MA 02114 USA. RP Hara, AK (reprint author), Mayo Clin Arizona, Dept Diagnost Radiol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM hara.amy@mayo.edu NR 30 TC 14 Z9 14 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2013 VL 201 IS 1 BP 33 EP 40 DI 10.2214/AJR.13.10556 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900030 PM 23789656 ER PT J AU Yee, J Keysor, KJ Kim, DH AF Yee, Judy Keysor, Kathryn J. Kim, David H. TI The Time Has Arrived for National Reimbursement of Screening CT Colonography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT colonography screening ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; EXTRACOLONIC FINDINGS; COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; ADENOMATOUS POLYPS; POPULATION; PREVALENCE; SURVEILLANCE; ACCURACY AB OBJECTIVE. CT colonography (CTC) has been fully validated as an accurate screening test for colorectal carcinoma and is being disseminated globally. There is an abundance of new literature addressing the prior concerns of the U. S. Preventive Services Task Force and the Centers for Medicare & Medicaid Services. Specific areas related to radiation dose, extracolonic findings, and generalizability of CTC to senior patients are discussed. CONCLUSION. The time has arrived for national reimbursement of CTC in the United States. C1 [Yee, Judy] San Francisco VA Med Ctr, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. [Yee, Judy] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Keysor, Kathryn J.] Amer Coll Radiol, Reston, VA USA. [Kim, David H.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Yee, J (reprint author), San Francisco VA Med Ctr, Dept Radiol & Biomed Imaging, 4150 Clement St, San Francisco, CA 94121 USA. EM judy.yee@ucsf.edu NR 42 TC 9 Z9 9 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2013 VL 201 IS 1 BP 73 EP 79 DI 10.2214/AJR.13.10656 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900034 PM 23789660 ER PT J AU Gunn, AJ Seethamraju, RT Hedgire, S Elmi, A Daniels, GH Harisinghani, MG AF Gunn, Andrew J. Seethamraju, Ravi T. Hedgire, Sandeep Elmi, Azadeh Daniels, Gilbert H. Harisinghani, Mukesh G. TI Imaging Behavior of the Normal Adrenal on Ferumoxytol-Enhanced MRI: Preliminary Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adrenal; ferumoxytol; ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) ID SUPERPARAMAGNETIC IRON-OXIDE; LYMPH-NODE METASTASES; CONTRAST AGENT; CANCER; FERUMOXTRAN-10; NANOPARTICLE; HEMOCHROMATOSIS; TUMORS; NECK; HEAD AB OBJECTIVE. Ultrasmall superparamagnetic iron oxide nanoparticles, such as ferumoxytol, produce decreased MR signal on susceptibility-inducing T2*-weighted sequences in tissues of the reticuloendothelial system. However, acute iron deposition in the adrenals has not been reported. The purpose of this article is to report our initial observations of the imaging behavior of the normal adrenals on ferumoxytol-enhanced T2*-weighted magnetic resonance imaging. SUBJECTS AND METHODS. Quantitative T2* imaging was performed at 3 T using a breath-hold monopolar multiecho gradient echo sequence with six equally spaced in-phase echoes in nine patients. Changes in signal-to-noise ratio (SNR) were analyzed prior to and 48 hours after ferumoxytol administration in the adrenals, liver and spleen (positive controls), and pancreas and skeletal muscle (negative controls). RESULTS. In comparison with unenhanced images, there was an average SNR decrease of 67.4% in the right adrenal, 77.6% in the left adrenal, 68.4% in the liver, 89.1% in the spleen, 15.0% in the pancreas, and 9.5% in skeletal muscle on T2*-weighted images obtained 48 hours after ferumoxytol administration. The decrease in SNR observed in the adrenals was significantly greater than that seen in the pancreas and skeletal muscle (left adrenal, p < 0.0001; right adrenal, p = 0.0002) and similar to that seen in the liver and spleen. CONCLUSION. The normal adrenal loses signal on ferumoxytol-enhanced T2*-weighted MRI. Acute iron deposition within the adrenals has not been previously described. The mechanism of ferumoxytol uptake in the adrenal and potential clinical applications warrant further investigation. C1 [Gunn, Andrew J.; Hedgire, Sandeep; Elmi, Azadeh; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02214 USA. [Gunn, Andrew J.; Hedgire, Sandeep; Elmi, Azadeh; Daniels, Gilbert H.; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Boston, MA 02214 USA. [Seethamraju, Ravi T.] Siemens Healthcare, MR Res & Dev, Boston, MA USA. [Daniels, Gilbert H.] Massachusetts Gen Hosp, Ctr Canc, Thyroid Unit, Boston, MA 02214 USA. [Daniels, Gilbert H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02214 USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02214 USA. RP Gunn, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02214 USA. EM agunn@partners.org FU National Institutes of Health FX This research was funded, in part, by a gastrointestinal Specialized Programs of Research Excellence (SPORE) grant from the National Institutes of Health. NR 23 TC 9 Z9 9 U1 0 U2 4 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 JUL PY 2013 VL 201 IS 1 BP 117 EP 121 DI 10.2214/AJR.12.9357 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900038 PM 23789664 ER PT J AU Ginat, DT Smith, ER Robertson, RL Scott, RM Schaefer, PW AF Ginat, Daniel T. Smith, Edward R. Robertson, Richard L. Scott, R. Michael Schaefer, Pamela W. TI Imaging After Direct and Indirect Extracranial-Intracranial Bypass Surgery SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE angiography; cerebral revascularization; CT; extracranial-intracranial bypass; MRI; synangiosis ID SUPERFICIAL TEMPORAL ARTERY; PEDIATRIC MOYAMOYA-DISEASE; SYMPTOMATIC CEREBRAL HYPERPERFUSION; BUR HOLE SURGERY; SURGICAL-MANAGEMENT; CLINICAL ARTICLE; PIAL SYNANGIOSIS; IC BYPASS; REVASCULARIZATION; ANASTOMOSIS AB OBJECTIVE. The purpose of this article is to describe the imaging features of different types of surgical cerebral revascularization techniques. CONCLUSION. Surgical cerebral revascularization involves direct and indirect techniques. Direct revascularization entails anastomosing a branch of the external carotid artery to a cerebral artery. Indirect revascularization involves delivering an extracranial vascular supply in proximity to the surface of the brain. The results of these techniques have distinctive imaging features. C1 [Ginat, Daniel T.; Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Smith, Edward R.; Scott, R. Michael] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Robertson, Richard L.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com OI Robertson, Richard/0000-0001-8811-4405 NR 43 TC 1 Z9 1 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 JUL PY 2013 VL 201 IS 1 BP W124 EP W132 DI 10.2214/AJR.12.9517 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900017 PM 23789684 ER PT J AU Kim, KW Shinagare, AB Krajewski, KM Howard, SA Jagannathan, JP Zukotynski, K Ramaiya, NH AF Kim, Kyung Won Shinagare, Atul B. Krajewski, Katherine M. Howard, Stephanie A. Jagannathan, Jyothi P. Zukotynski, Katherine Ramaiya, Nikhil H. TI Update on Imaging of Vulvar Squamous Cell Carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE gynecology; imaging; MRI; PET; vulvar carcinoma ID LYMPH-NODE METASTASES; GUIDED CYTOLOGY; CANCER; MANAGEMENT; ULTRASOUND; TOMOGRAPHY AB OBJECTIVE. The purpose of this article is to describe the advantages and diagnostic and prognostic implications of imaging in the management of vulvar carcinoma. CONCLUSION. As the treatment of vulvar carcinoma evolves to tailored surgery and chemoradiation therapy to reduce morbidity, the importance of pretreatment assessment of vulvar carcinoma increases. Advances in imaging, such as pelvic MRI and PET, add to the benefits of clinical evaluation in pretreatment planning, assessment of response to chemoradiation therapy, and posttreatment surveillance. C1 [Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Howard, Stephanie A.; Jagannathan, Jyothi P.; Zukotynski, Katherine; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Seoul Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. RP Kim, KW (reprint author), Univ Ulsan, Coll Med, Seoul Asan Med Ctr, Dept Radiol, Pungnap 2 Dong, Seoul 138736, South Korea. EM medimash@gmail.com NR 30 TC 4 Z9 4 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2013 VL 201 IS 1 BP W147 EP W157 DI 10.2214/AJR.12.9594 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900020 PM 23789687 ER PT J AU Malguria, N Hanley, M Steigner, M Kumamaru, KK Wake, N Zenati, M Rybicki, FJ AF Malguria, Nagina Hanley, Michael Steigner, Michael Kumamaru, Kanako K. Wake, Nicole Zenati, Marco Rybicki, Frank J. TI Static and Cine CT Imaging to Identify and Characterize Mediastinal Adhesions as a Potential Complication for Patients Underdoing "Redo Sternotomy" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adhesions; redo sternotomy ID COMPUTED-TOMOGRAPHY; CORONARY; ANGIOGRAPHY AB OBJECTIVE. The purpose of this article is to describe the image acquisition, identification, and reporting of postoperative adhesions in patients undergoing CT for "redo sternotomy" surgical planning. CONCLUSION. Adhesions appear as linear fibrous bands that join structures in the mediastinum viewed on static images. Confirmation by cine imaging shows deformation of mediastinal structures. Identification and reporting of adhesions will likely guide surgeons to safer interventions. C1 [Malguria, Nagina; Hanley, Michael; Steigner, Michael; Kumamaru, Kanako K.; Wake, Nicole; Rybicki, Frank J.] Brigham & Womens Hosp, Dept Radiol, Appl Imaging Sci Lab, Boston, MA 02115 USA. [Malguria, Nagina; Hanley, Michael; Steigner, Michael; Kumamaru, Kanako K.; Wake, Nicole; Zenati, Marco; Rybicki, Frank J.] Harvard Univ, Sch Med, Boston, MA USA. [Malguria, Nagina] Boston VA HealthCare Syst, Dept Radiol, West Roxbury, MA 02132 USA. [Zenati, Marco] VA Boston HealthCare Syst, Dept Cardiothorac Surg, West Roxbury, MA USA. [Zenati, Marco] Brigham & Womens Hosp, Dept Cardiothorac Surg, Boston, MA 02115 USA. RP Malguria, N (reprint author), Boston VA HealthCare Syst, Dept Radiol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM nmalguria@gmail.com NR 8 TC 3 Z9 3 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 JUL PY 2013 VL 201 IS 1 BP W72 EP W74 DI 10.2214/AJR.12.9406 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900009 PM 23789699 ER PT J AU Moshiri, M Osman, S Robinson, TJ Khandelwal, S Bhargava, P Rohrmann, CA AF Moshiri, Mariam Osman, Sherif Robinson, Tracy J. Khandelwal, Saurabh Bhargava, Puneet Rohrmann, Charles A. TI Evolution of Bariatric Surgery: A Historical Perspective SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE bariatric; biliopancreatic diversion; gastric bypass; gastrojejunostomy; gastroplasty; jejunocolic ID VERTICAL BANDED GASTROPLASTY; MORBID-OBESITY; JEJUNOILEAL BYPASS; SURGICAL-TREATMENT; BILIOPANCREATIC DIVERSION; DUODENAL SWITCH; GASTRIC BYPASS; COMPLICATIONS; OPERATIONS AB OBJECTIVE. Older legacy bariatric surgical procedures, including jejunocolic bypass, jejunoileal bypass, vertical banded gastroplasty, and biliopancreatic diversion, are no longer performed. Biliopancreatic diversion with duodenal switch is still performed in select centers. Although the legacy procedures are no longer performed, there are still patients who have undergone these surgeries in the past who are currently either under continuous surveillance or are being evaluated for surgical conversion or revision because of complications or weight regain. The purpose of this article is to describe the evolutionary development of various bariatric surgical techniques and the associated surgical anatomy. Because these procedures are no longer performed, only limited imaging of legacy bariatric surgeries is available for radiologic demonstration. CONCLUSION. Although earlier bariatric surgical techniques are no longer favored, there are still patients who underwent these procedures who require imaging evaluation for clinical follow-up or surgical revision. Understanding the radiologic-surgical anatomy of these older bariatric procedures can help in the prompt and appropriate management of these patients. C1 [Moshiri, Mariam; Osman, Sherif; Robinson, Tracy J.; Bhargava, Puneet; Rohrmann, Charles A.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Khandelwal, Saurabh] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. RP Moshiri, M (reprint author), Univ Washington, Sch Med, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM Moshiri@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 27 TC 12 Z9 12 U1 0 U2 9 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 JUL PY 2013 VL 201 IS 1 BP W40 EP W48 DI 10.2214/AJR.12.10131 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900005 PM 23789695 ER PT J AU Nishino, M Cardarella, S Jackman, DM Ramaiya, NH Rabin, MS Hatabu, H Janne, PA Johnson, BE AF Nishino, Mizuki Cardarella, Stephanie Jackman, David M. Ramaiya, Nikhil H. Rabin, Michael S. Hatabu, Hiroto Jaenne, Pasi A. Johnson, Bruce E. TI RECIST 1.1 in NSCLC Patients With EGFR Mutations Treated With EGFR Tyrosine Kinase Inhibitors: Comparison With RECIST 1.0 SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE epidermal growth factor receptor (EGFR); lung cancer; non-small cell lung cancer (NSCLC); Response Evaluation Criteria in Solid Tumors (RECIST); tumor response assessment; tyrosine kinase inhibitor ID CELL LUNG-CANCER; RESPONSE EVALUATION CRITERIA; GROWTH-FACTOR RECEPTOR; GUIDELINE VERSION 1.1; SOLID TUMORS; 1ST-LINE TREATMENT; OPEN-LABEL; GEFITINIB; ERLOTINIB; CHEMOTHERAPY AB OBJECTIVE. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 has been rapidly accepted in clinical trials as a standard measure to assess tumor response to therapy and is expected to improve response assessment, especially in genomically defined patients. The impact of RECIST 1.1 was compared with RECIST 1.0 in non-small cell lung cancer (NSCLC) patients with sensitizing epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors. MATERIALS AND METHODS. Seventy patients with advanced NSCLC harboring sensitizing EGFR mutations treated with a first-line EGFR tyrosine kinase inhibitor were retrospectively studied. Tumor measurements and response assessment were performed using RECIST 1.0 and RECIST 1.1. The number of target lesions, the percentage change at the initial follow-up, best response, and time to progression were compared between RECIST 1.1 and RECIST 1.0. RESULTS. The number of target lesions identified using RECIST 1.1 was significantly lower compared with that using RECIST 1.0 (mean, 2.7 and 2.0, respectively; p < 0.0001; paired Student t test), with a decrease in 31 patients (44%). The initial proportional changes of the target lesion measurements had high correlation between the two criteria (R-2 = 0.8070), with concordant response assessment in 66 patients (94%). The best response showed almost perfect agreement (kappa(w) = 0.970). Time to progression (TTP) did not differ between the two criteria in 52 patients (74%), was longer by RECIST 1.1 in 15 patients (21%), and was shorter by RECIST 1.1 in three patients (4%). CONCLUSION. RECIST 1.1 provided highly concordant response assessment with a decreased number of target lesions compared with RECIST 1.0 in advanced NSCLC patients harboring sensitizing EGFR mutations treated with an EGFR tyrosine kinase inhibitor. RECIST 1.1 altered TTP in 25% of patients compared with RECIST 1.0. C1 [Nishino, Mizuki; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Nishino, Mizuki; Ramaiya, Nikhil H.; Hatabu, Hiroto] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Nishino, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM mizuki_nishino@dfci.harvard.edu FU National Cancer Institute [1K23CA157631]; National Institutes of Health [1R01CA114465-01, 5R21 CA11627-02]; National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [2P50CA090578-06]; Genentech; Doris and William Krupp Research Fund in Thoracic Oncology and American Society of Clinical Oncology Translational Research Professorship FX M. Nishino was supported by grant 1K23CA157631 from the National Cancer Institute. B. E. Johnson and P. A. Janne were supported by grant 1R01CA114465-01 from the National Institutes of Health and grant 2P50CA090578-06 from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer as well as grants from Genentech and the Doris and William Krupp Research Fund in Thoracic Oncology and American Society of Clinical Oncology Translational Research Professorship. H. Hatabu was supported by grant 5R21 CA11627-02 from the National Institutes of Health. NR 31 TC 12 Z9 14 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2013 VL 201 IS 1 BP W64 EP W71 DI 10.2214/AJR.12.9668 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900008 PM 23789698 ER PT J AU Shinagare, AB Jagannathan, JP Krajewski, KM Ramaiya, NH AF Shinagare, Atul Bhanudas Jagannathan, Jyothi P. Krajewski, Katherine M. Ramaiya, Nikhil H. TI Liver Metastases in the Era of Molecular Targeted Therapy: New Faces of Treatment Response SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE atypical treatment response; hepatic metastases; liver metastases; metastases; molecular targeted therapy; tumor response criteria ID RENAL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMOR; IMAGING TECHNIQUES; IMATINIB MESYLATE; SOLID TUMORS; CRITERIA; CT; RECURRENCE; SUNITINIB; RECIST AB OBJECTIVE. The liver is one of the most common sites of metastatic disease. The increasing use of molecular targeted therapy, including antiangiogenic agents, mammalian target of rapamycin inhibitors, and various monoclonal antibodies, for the treatment of various carcinomas and sarcomas has rendered use of simple size measurements for the assessment of treatment response inadequate. Several atypical patterns of treatment response, at times mimicking tumor progression, are increasingly seen, leading to confusion. The purpose of this article is to familiarize the reader with the unusual patterns in which liver metastases respond to molecular targeted therapy and help differentiate treatment response mimicking progression (pseudoprogression) from true progression. CONCLUSION. In the era of molecular targeted therapy, every radiologist who interprets oncologic studies needs to be aware of the unusual patterns of treatment response and should be able to differentiate pseudoprogression of liver metastases from true progression because this distinction has an important impact on clinical management. C1 [Shinagare, Atul Bhanudas; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Shinagare, Atul Bhanudas; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org NR 25 TC 10 Z9 11 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 JUL PY 2013 VL 201 IS 1 BP W15 EP W28 DI 10.2214/AJR.12.9498 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169HX UT WOS:000320771900003 PM 23789688 ER PT J AU Friedman, DJ Bender, SR Markowitz, SM Lerman, BB Okin, PM AF Friedman, Daniel J. Bender, Seth R. Markowitz, Steven M. Lerman, Bruce B. Okin, Peter M. TI T-Wave Alternans and ST Depression Assessment Identifies Low Risk Individuals with Ischemic Cardiomyopathy in the Absence of Left Ventricular Hypertrophy SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE electrocardiography; hypertrophy; electrophysiology; cardiomyopathy ID SUDDEN CARDIAC DEATH; END-POINT REDUCTION; MYOCARDIAL-INFARCTION; HYPERTENSIVE PATIENTS; DEFIBRILLATOR IMPLANTATION; CARDIOVERTER-DEFIBRILLATOR; LOSARTAN INTERVENTION; HEART-FAILURE; QRS DURATION; QT INTERVAL AB Background: Although ECG left ventricular hypertrophy (LVH) by Cornell product (CP) predicts increased mortality in patients with ischemic cardiomyopathy (ICM), those without CP LVH remain at relatively high risk. We examined whether T-wave alternans (TWA) testing and ST depression can improve risk stratification in these patients. Methods and Results: This study examined 317 patients with ICM, nonsustained ventricular tachycardia, and a resting ECG in sinus rhythm, who presented for electrophysiology and TWA testing, and potential implantable cardioverter defibrillator (ICD) implantation. LVH was defined by CP :[(R-aVL + S-V3) + 6 mm in women] x QRS duration > 2440 mm * msec. ST depression was examined as a categorical variable using an established threshold of depression of >= 50 mu V in V-5 or V-6. In Cox multivariate models, abnormal TWA testing and ST depression were independent predictors of mortality in patients without CP LVH (HR 2.52, CI 1.09-5.80, P = 0.030 and HR 2.87, CI 1.41-5.81, P = 0.004, respectively). Individuals with no LVH by CP, normal TWA, and no significant ST depression, comprised 23% of the study population and had a 5.6% 3-year mortality, compared to an overall 20% mortality. Conclusions: TWA and ST depression testing are strong predictors of mortality among ICM patients without CP LVH, with normal testing conversely predicting low 3-year mortality. Thus, risk assessment with TWA testing and a resting ECG can identify ICM patients at low risk who may be less likely to benefit from ICD implantation. C1 [Friedman, Daniel J.; Bender, Seth R.; Markowitz, Steven M.; Lerman, Bruce B.; Okin, Peter M.] Weill Cornell Med Coll, Greenberg Div Cardiol, New York, NY 10065 USA. [Friedman, Daniel J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Okin, PM (reprint author), Weill Cornell Med Coll, 525 East 68 St, New York, NY 10065 USA. EM pokin@med.cornell.edu OI Friedman, Daniel /0000-0001-5791-1954 FU Novartis Pharmaceuticals FX Drs. Bender, Friedman, and Lerman have no disclosures. Dr. Markowitz has received honoraria from Medtronic, Boston Scientific, St. Jude Medical, and Biotronik. Dr. Okin serves on a medical advisory board for GE Medical Systems, Inc. and serves as a consultant for and receives grant support from Novartis Pharmaceuticals. NR 36 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JUL PY 2013 VL 18 IS 4 BP 359 EP 368 DI 10.1111/anec.12051 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 187ZG UT WOS:000322159800007 PM 23879276 ER PT J AU Wolpin, BM O'Reilly, EM Ko, YJ Blaszkowsky, LS Rarick, M Rocha-Lima, CM Ritch, P Chan, E Spratlin, J Macarulla, T McWhirter, E Pezet, D Lichinitser, M Roman, L Hartford, A Morrison, K Jackson, L Vincent, M Reyno, L Hidalgo, M AF Wolpin, B. M. O'Reilly, E. M. Ko, Y. J. Blaszkowsky, L. S. Rarick, M. Rocha-Lima, C. M. Ritch, P. Chan, E. Spratlin, J. Macarulla, T. McWhirter, E. Pezet, D. Lichinitser, M. Roman, L. Hartford, A. Morrison, K. Jackson, L. Vincent, M. Reyno, L. Hidalgo, M. TI Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; clinical trial; gemcitabine; metastatic disease; pancreatic cancer; prostate stem cell antigen ID STEM-CELL ANTIGEN; COOPERATIVE-ONCOLOGY-GROUP; RESISTANT PROSTATE-CANCER; GENOME-WIDE ASSOCIATION; MONOCLONAL-ANTIBODY; GENETIC-VARIATION; BLADDER-CANCER; TUMOR-GROWTH; PSCA; SUSCEPTIBILITY AB Background: We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer. Patients and methods: Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression. Results: Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% Cl, 31.9-57.5) in the gemcitabine arm and 60.9% (95% Cl, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup. Conclusions: This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. C1 [Wolpin, B. M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [O'Reilly, E. M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ko, Y. J.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Blaszkowsky, L. S.] Massachusettes Gen Hosp, Boston, MA USA. [Rocha-Lima, C. M.] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Ritch, P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Chan, E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Spratlin, J.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Macarulla, T.] Hosp Valle De Hebron, Serv Oncol, Barcelona, Spain. [McWhirter, E.] Juravinski Canc Ctr, Hamilton, ON, Canada. [Pezet, D.] Ctr Hosp Univ Estaing, INSERM, U1071, Clermont Ferrand, France. [Lichinitser, M.] State Inst Blokhin Canc Res Ctr RAMS, Moscow, Russia. [Roman, L.] State Healthcare Inst Leningrad Reg Oncol Dispens, St Petersburg, Russia. [Hartford, A.; Morrison, K.; Jackson, L.; Vincent, M.; Reyno, L.] Agensys Inc, Santa Monica, CA USA. [Hidalgo, M.] Ctr Integral Oncol Clara Campal, Madrid, Spain. [Hidalgo, M.] Ctr Nacl Invest Oncol, Madrid, Spain. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU Agensys, Inc. FX This work was supported by Agensys, Inc., an affiliate of Astellas Pharmaceuticals Inc. NR 42 TC 16 Z9 16 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2013 VL 24 IS 7 BP 1792 EP 1801 DI 10.1093/annonc/mdt066 PG 10 WC Oncology SC Oncology GA 184HV UT WOS:000321881600012 PM 23448807 ER PT J AU Tolaney, SM Najita, J Sperinde, J Huang, W Chen, WY Savoie, J Fornier, M Winer, EP Bunnell, C Krop, IE AF Tolaney, S. M. Najita, J. Sperinde, J. Huang, W. Chen, W. Y. Savoie, J. Fornier, M. Winer, E. P. Bunnell, C. Krop, I. E. TI A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE breast; cancer; HER2; ixabepilone; trastuzumab ID HER2; TAXANE; DOCETAXEL; ANTHRACYCLINE; CAPECITABINE; PACLITAXEL; EFFICACY; TRIAL; PLUS; MICROTUBULES AB Background: A multicenter NCI-sponsored phase II study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer. Patients and methods: Two cohorts were enrolled: cohort 1 had received no prior chemotherapy or trastuzumab for metastatic disease and cohort 2 had received 1-2 prior trastuzumab-containing regimens for metastatic disease. Patients in both cohorts received ixabepilone 40 mg/m(2) as a 3-h infusion and trastuzumab on day 1 of a 21-day cycle. Tumor biomarkers that may predict response to trastuzumab were explored. Results: Thirty-nine women entered the study with 15 patients in cohort 1 and 24 patients in cohort 2. Across both cohorts, the overall RR was 44%, with a clinical benefit rate (CR + PR + SD for at least 24 weeks) of 56%. Treatment-related toxic effects included neuropathy (grade >= 2, 56%), leukopenia (grade >= 2, 26%), myalgias (grade >= 2, 21%), neutropenia (grade >= 2, 23%), and anemia (grade >= 2, 18%). Conclusions: This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has encouraging activity as first and subsequent line therapy for metastatic breast cancer. C1 [Tolaney, S. M.; Chen, W. Y.; Savoie, J.; Winer, E. P.; Bunnell, C.; Krop, I. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Najita, J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Sperinde, J.] Monogram Biosci Inc, Dept Res & Dev, San Francisco, CA USA. [Huang, W.] Monogram Biosci Inc, Dept Clin Res, San Francisco, CA USA. [Chen, W. Y.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Fornier, M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Tolaney, SM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 1257, Boston, MA 02215 USA. EM stolaney@partner.org FU Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) FX This work was supported by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) (no grant number). NR 29 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2013 VL 24 IS 7 BP 1841 EP 1847 DI 10.1093/annonc/mdt121 PG 7 WC Oncology SC Oncology GA 184HV UT WOS:000321881600019 PM 23559151 ER PT J AU Seah, DS Scottt, SM Najita, J Openshaw, T Krag, K Frank, E Sohl, J Stadler, ZK Garrett, M Silverman, SG Peppercorn, J Winer, EP Come, SE Lin, NU AF Seah, D. S. Scottt, S. M. Najita, J. Openshaw, T. Krag, K. Frank, E. Sohl, J. Stadler, Z. K. Garrett, M. Silverman, S. G. Peppercorn, J. Winer, E. P. Come, S. E. Lin, Nancy U. TI Attitudes of patients with metastatic breast cancer toward research biopsies SO ANNALS OF ONCOLOGY LA English DT Article DE metastatic breast cancer; patient's preferences; research biopsies ID RANDOMIZED CLINICAL-TRIALS; ANTICANCER AGENTS; TUMOR-BIOPSIES; PARTICIPATION; ONCOLOGY; EXPERIENCE; OUTCOMES AB Background: Research studies involving human tissue are increasingly common. However, patients' attitudes toward research biopsies are not well characterized, particularly when the biopsies are carried out outside the context of therapeutic trials. Patients and methods: One hundred sixty patients with metastatic breast cancer (MBC) from two academic (n = 80) and two community (n = 80) hospitals completed a 29-item self-administered survey to evaluate their willingness to consider providing research purposes only biopsies (RPOBs) (as a stand-alone procedure) and additional biopsies (ABs) (additional needle passes at the time of a clinically indicated biopsy). Results: Eighty-two (51%) of 160 patients would consider having RPOBs, of which 42 (53%) and 40 (50%) patients were from academic and community hospitals, respectively. Patients who had more prior biopsies were less likely to consider RPOBs (RR = 0.6, 95% Cl: 0.4-1.0, P = 0.03). Of 160 patients, 115 (72%) patients would consider having ABs. Of these, 64 (80%) and 51(64%) patients from academic and community hospitals, respectively, would consider ABs (RR = 1.2, 95% Cl: 1.0-1.5, P = 0.03). Conclusions: Many patients with MBC in both academic and community settings report willingness to consider undergoing biopsies for research. Further research is needed to understand ethical, logistical and provider-based barriers to broader participation in such studies. C1 [Seah, D. S.; Frank, E.; Sohl, J.; Winer, E. P.; Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Scottt, S. M.; Come, S. E.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Najita, J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Openshaw, T.; Garrett, M.] Canc Care Maine, Dept Med Oncol, Bangor, Gwynedd, Wales. [Stadler, Z. K.] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA. [Silverman, S. G.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Peppercorn, J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, 450 Brookline Ave, Boston, MA 02215 USA. EM nlin@partners.org FU Metastatic Research Fund; Nancy and Randy Berry Junior Faculty Award; Karen Webster & David Evans Metastatic Research Fund FX This work was supported by Metastatic Research Fund-anonymous donor, Nancy and Randy Berry Junior Faculty Award and the Karen Webster & David Evans Metastatic Research Fund. NR 22 TC 7 Z9 7 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 JUL PY 2013 VL 24 IS 7 BP 1853 EP 1859 DI 10.1093/annonc/mdt067 PG 7 WC Oncology SC Oncology GA 184HV UT WOS:000321881600021 PM 23493137 ER PT J AU Discacciati, A Orsini, N Andersson, SO Andren, O Johansson, JE Mantzoros, CS Wolk, A AF Discacciati, A. Orsini, N. Andersson, S. -O. Andren, O. Johansson, J. -E. Mantzoros, C. S. Wolk, A. TI Coffee consumption and risk of localized, advanced and fatal prostate cancer: a population-based prospective study SO ANNALS OF ONCOLOGY LA English DT Article DE coffee; epidemiology; prospective cohort study; prostate cancer ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; ADIPONECTIN; MEN; COHORT; ANTIOXIDANTS; MORTALITY; HEALTH; DIET; ASSOCIATIONS AB Background: The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. Materials and methods: A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). Results: For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (P-interaction = 0.03); the inverse association was stronger among overweight and obese men (BMI >= 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)). Conclusions: We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men. C1 [Discacciati, A.; Orsini, N.; Wolk, A.] Karolinska Inst, Inst Environm Med, Div Epidemiol, Unit Nutr Epidemiol, S-17177 Stockholm, Sweden. [Andersson, S. -O.; Andren, O.; Johansson, J. -E.] Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden. [Andersson, S. -O.; Andren, O.; Johansson, J. -E.] Orebro Univ Hosp, Dept Urol, Orebro, Sweden. [Mantzoros, C. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, C. S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. RP Wolk, A (reprint author), Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Box 210, S-17177 Stockholm, Sweden. EM alicja.wolk@ki.se FU Swedish Cancer Foundation (Cancerfonden); Swedish Research Council/Committee for Infrastructure FX This work was supported by research grants from the Swedish Cancer Foundation (Cancerfonden) and from the Swedish Research Council/Committee for Infrastructure. NR 39 TC 14 Z9 16 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2013 VL 24 IS 7 BP 1912 EP 1918 DI 10.1093/annonc/mdt105 PG 7 WC Oncology SC Oncology GA 184HV UT WOS:000321881600030 PM 23508823 ER PT J AU Setlur, J Maturo, S Hartnick, CJ AF Setlur, Jennifer Maturo, Stephen Hartnick, Christopher J. TI Novel Method for Laryngotracheal Reconstruction: Combining Single- and Double-Stage Techniques SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE airway surgery; laryngotracheal reconstruction; pediatrics; subglottic stenosis; tracheostomy ID SUBGLOTTIC STENOSIS; MANAGEMENT; CHILDREN; INFANTS AB Objectives: Traditional open techniques for laryngotracheal reconstruction are either single- or double-stage procedures. Some patients may benefit from the presence of a long, single-tube stent, such as an endotracheal tube, but their predicted need for a 2-stage procedure and a persistent tracheostomy is high. We describe a novel technique for airway reconstruction that combines the methods of both single- and double-stage procedures. Methods: We present a retrospective review of 4 patients. All patients underwent laryngotracheal reconstruction by a single surgeon. After the operation, the airway was stented with nasotracheal intubation. A small stent, fashioned from an endotracheal tube, was placed in the tracheostoma to keep it patent. The patients subsequently underwent extubation and replacement of the tracheostomy tube. Results: The study included 1 patient with grade 4 subglottic stenosis, 2 patients with grade 3 subglottic stenosis, and 1 patient with a posterior glottic scar. All were tracheostomy tube dependent. Serial bronchoscopy was used to follow the patients for a minimum of 9 months after the operation. All 4 patients have since met the criteria for decannulation. Conclusions: This hybrid reconstruction merges the advantages of both the single- and double-stage procedures. It adds versatility to the surgical toolbox for airway reconstruction. C1 [Setlur, Jennifer; Maturo, Stephen; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Setlur, Jennifer; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 19 TC 5 Z9 6 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 2013 VL 122 IS 7 BP 445 EP 449 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 184HM UT WOS:000321880700006 PM 23951696 ER PT J AU Azadani, AN Chitsaz, S Mannion, A Mookhoek, A Wisneski, A Guccione, JM Hope, MD Ge, L Tseng, EE AF Azadani, Ali N. Chitsaz, Sam Mannion, Alex Mookhoek, Aart Wisneski, Andrew Guccione, Julius M. Hope, Michael D. Ge, Liang Tseng, Elaine E. TI Biomechanical Properties of Human Ascending Thoracic Aortic Aneurysms SO ANNALS OF THORACIC SURGERY LA English DT Article ID RUPTURE-RISK; MECHANICAL-PROPERTIES; WALL STRESS; ASSOCIATION; PREDICTION; DIAMETER; STRENGTH; BEHAVIOR; AGE AB Background. Surgical management of ascending thoracic aortic aneurysms (aTAAs) relies on maximum diameter, growth rate, and presence of connective tissue disorders. However, dissection and rupture do occur in patients who do not meet criteria for surgical repair. This study investigated the mechanical properties of aTAAs compared with normal human ascending aortas for eventual development of biomechanical aTAA risk models. Methods. aTAA specimens (n = 18) were obtained from patients undergoing surgical aneurysm repair, and fresh, healthy ascending aortas (n = 19) as controls were obtained from the transplant donor network. Biaxial stretch testing was performed to obtain tissue mechanical properties. Patient-specific aTAA physiologic stress was calculated based on preoperative computed tomography diameter. aTAA and ascending aorta tissue stiffness at respective physiologic stress were determined. Results. Physiologic stress of aTAA was significantly greater (241.6 +/- 59.4 kPa) than the 74 kPa for normal controls. Tissue stiffness of aTAAs was significantly greater than that of the ascending aortas at their respective physiologic stresses in the circumferential (3041.4 +/- 1673.7 vs 905.1 +/- 358.9 kPa, respectively; p < 0.001) and longitudinal (3498.2 +/- 2456.8 vs 915.3 +/- 368.9 kPa, respectively; p < 0.001) directions. Tissue stiffness of aTAAs positively correlated with aTAA diameter but did not correlate with patient age. No correlation was found between aTAA physiologic stress level and maximum aTAA diameter. Conclusions. aTAAs are much stiffer than normal ascending aortas at their respective physiologic stress, which was also significantly greater in ATAAs than ascending aortas. Patient-specific physiologic stress did not correlate with maximum aTAA diameter, and patient-specific aTAA wall stress may be a useful variable to predict adverse aTAA events. (C) 2013 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Med Ctr, Dept Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Erasmus Univ, Med Ctr, Dept Cardiothorac Surg, Rotterdam, Netherlands. RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, 500 Parnassus Ave,Ste 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 NR 23 TC 19 Z9 19 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2013 VL 96 IS 1 BP 50 EP 58 DI 10.1016/j.athoracsur.2013.03.094 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 182KP UT WOS:000321741300019 PM 23731613 ER PT J AU Fitzsimons, MG Walton, K Makar, R Dzik, W Kuter, D Vlahakes, GJ AF Fitzsimons, Michael G. Walton, Ken Makar, Robert Dzik, Walter Kuter, David Vlahakes, Gus J. TI Redo Aortic Valve Replacement in a Patient With Immunoglobulin A Deficiency and Hemophilia A SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID ANAPHYLACTIC TRANSFUSION REACTIONS AB Immunoglobulin A (IgA) deficiency may result in the development of anti-IgA antibodies. Such antibodies may result in anaphylaxis when patients receive standard blood products. Hemophilia A is a deficiency of clotting factor VIII that results in a significant coagulopathy and bleeding in the perioperative period unless precautions are taken. We present a case of successful management of combined hemophilia A and IgA deficiency in a patient undergoing repeated sternotomy for aortic valve replacement. (C) 2013 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Div Cardiac Anesthesia, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Lahey Clin Fdn, Dept Anesthesiol, Burlington, MA USA. Massachusetts Gen Hosp, Blood Transfus Serv, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Dept Surg, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Div Cardiac Anesthesia, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 9 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2013 VL 96 IS 1 BP 311 EP 313 DI 10.1016/j.athoracsur.2012.12.006 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 182KP UT WOS:000321741300062 PM 23816085 ER PT J AU Katiyar, SK Athar, M AF Katiyar, Santosh K. Athar, Mohammad TI Grape Seeds: Ripe for Cancer Chemoprevention SO CANCER PREVENTION RESEARCH LA English DT Article ID CELL LUNG-CANCER; FACTOR BINDING PROTEIN-3; PROSTATE TUMOR-GROWTH; SKH-1 HAIRLESS MICE; PROANTHOCYANIDINS INHIBIT; PANCREATIC-CANCER; MOUSE SKIN; KAPPA-B; EXTRACT; ACTIVATION AB A wide variety of phytochemicals, mostly flavonoids or polyphenolics, have been shown to possess anticarcinogenic activities. Among these are the grape seed proanthocyanidins (GSPs), which are the active ingredients of grape seed extract (GSE). Substantial in vitro and preclinical in vivo studies have shown the chemopreventive efficacy of GSPs against various forms of cancers in different tumor models. In this issue of the journal, Derry and colleagues show that administration of GSE in the diet reduces azoxymethane-induced colon carcinogenesis in an A/J mouse model. The results of this innovative and comprehensive study indicate that inhibition of azoxymethane- induced colon cancer by dietary GSE is mediated through the induction of apoptosis that is associated with alterations in microRNA (miRNA) and cytokine expression profiles as well as beta-catenin signaling. Notably, the demonstration that miRNA expression is affected by dietary GSE suggests a novel underlying mechanism for the chemopreventive action of GSE in colon cancer and, potentially, other cancers. (c) 2013 AACR. C1 [Katiyar, Santosh K.; Athar, Mohammad] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration Merit Review Award; NIH [CA166883] FX The work reported from the author's laboratory is supported by the Veterans Administration Merit Review Award (to S.K. Katiyar) and NIH (CA166883; to S.K. Katiyar). NR 35 TC 6 Z9 8 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUL PY 2013 VL 6 IS 7 BP 617 EP 621 DI 10.1158/1940-6207.CAPR-13-0193 PG 5 WC Oncology SC Oncology GA 174YR UT WOS:000321195000001 PM 23771521 ER PT J AU Ueno, T Dutta, P Keliher, E Leuschner, F Majmudar, M Marinelli, B Iwamoto, Y Figueiredo, JL Christen, T Swirski, FK Libby, P Weissleder, R Nahrendorf, M AF Ueno, Takuya Dutta, Partha Keliher, Edmund Leuschner, Florian Majmudar, Maulik Marinelli, Brett Iwamoto, Yoshiko Figueiredo, Jose-Luiz Christen, Thomas Swirski, Filip K. Libby, Peter Weissleder, Ralph Nahrendorf, Matthias TI Nanoparticle PET-CT Detects Rejection and Immunomodulation in Cardiac Allografts SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE heart transplantation; imaging; macrophage; positron emission tomography; computed tomography ID ACUTE MYOCARDIAL-INFARCTION; IRON-OXIDE PARTICLES; HEART-TRANSPLANTATION; SPLENIC RESERVOIR; MACROPHAGES; ATHEROSCLEROSIS; MONOCYTES; SURVIVAL; BIOPSIES AB Background Macrophages predominate among the inflammatory cells in rejecting allografts. These innate immune cells, in addition to allospecific T cells, can damage cardiomyocytes directly. Methods and Results We explored whether sensitive positron emission tomography-computed tomography (PET-CT) imaging of macrophages-avid nanoparticles detects rejection of heart allografts in mice. In addition, we used the imaging method to follow the immunomodulatory impact of angiotensin-converting enzyme inhibitor therapy on myeloid cells in allografts. Dextran nanoparticles were derivatized with the PET isotope copper-64 and imaged 7 days after transplantation. C57BL/6 recipients of BALB/c allografts displayed robust positron emission tomography signal (standard uptake value allograft, 2.8 +/- 0.3; isograft control, 1.7 +/- 0.2; P<0.05). Autoradiography and scintillation counting confirmed the in vivo findings. We then imaged the effects of angiotensin-converting enzyme inhibitor (5 mg/kg enalapril). Angiotensin-converting enzyme inhibitor significantly decreased nanoparticle signal (P<0.05). Histology and flow cytometry showed a reduced number of myeloid cells in the graft, blood, and lymph nodes and diminished antigen presentation (P<0.05 versus untreated allografts). Angiotensin-converting enzyme inhibitor also significantly prolonged allograft survival (12 versus 7 days; P<0.0001). Conclusions Nanoparticle macrophage PET-CT detects heart transplant rejection and predicts organ survival by reporting on myeloid cells. C1 [Ueno, Takuya; Dutta, Partha; Keliher, Edmund; Leuschner, Florian; Majmudar, Maulik; Marinelli, Brett; Iwamoto, Yoshiko; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Majmudar, Maulik; Figueiredo, Jose-Luiz; Christen, Thomas; Libby, Peter] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St Boston, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU National Heart, Lung, and Blood Institute [R01HL095629, R01HL114477, HHSN268201000044C]; American Heart Association [11SDG5150000]; American Society of Transplantation Basic Science Fellowship Grant [AST-129]; NIH T32 training grant [T32-HL094301] FX This work was funded by grants from the National Heart, Lung, and Blood Institute (R01HL095629, R01HL114477, contract No. HHSN268201000044C). Dr Ueno is a recipient of the American Heart Association Scientist Development Grant (11SDG5150000). Dr Dutta is a recipient of the American Society of Transplantation Basic Science Fellowship Grant (AST-129). Dr Majmudar was supported by an NIH T32 training grant (T32-HL094301). NR 26 TC 11 Z9 11 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JUL PY 2013 VL 6 IS 4 BP 568 EP 573 DI 10.1161/CIRCIMAGING.113.000481 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 185EJ UT WOS:000321947900016 PM 23771986 ER PT J AU Wasfy, JH Rosenfield, K Zelevinsky, K Sakhuja, R Lovett, A Spertus, JA Wimmer, NJ Mauri, L Normand, SLT Yeh, RW AF Wasfy, Jason H. Rosenfield, Kenneth Zelevinsky, Katya Sakhuja, Rahul Lovett, Ann Spertus, John A. Wimmer, Neil J. Mauri, Laura Normand, Sharon-Lise T. Yeh, Robert W. TI A Prediction Model to Identify Patients at High Risk for 30-Day Readmission After Percutaneous Coronary Intervention SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE outcomes research; percutaneous coronary intervention; performance measures ID HOSPITAL READMISSION; REPEAT REVASCULARIZATION; RATES AB Background The Affordable Care Act creates financial incentives for hospitals to minimize readmissions shortly after discharge for several conditions, with percutaneous coronary intervention (PCI) to be a target in 2015. We aimed to develop and validate prediction models to assist clinicians and hospitals in identifying patients at highest risk for 30-day readmission after PCI. Methods and Results We identified all readmissions within 30 days of discharge after PCI in nonfederal hospitals in Massachusetts between October 1, 2005, and September 30, 2008. Within a two-thirds random sample (Developmental cohort), we developed 2 parsimonious multivariable models to predict all-cause 30-day readmission, the first incorporating only variables known before cardiac catheterization (pre-PCI model), and the second incorporating variables known at discharge (Discharge model). Models were validated within the remaining one-third sample (Validation cohort), and model discrimination and calibration were assessed. Of 36060 PCI patients surviving to discharge, 3760 (10.4%) patients were readmitted within 30 days. Significant pre-PCI predictors of readmission included age, female sex, Medicare or State insurance, congestive heart failure, and chronic kidney disease. Post-PCI predictors of readmission included lack of -blocker prescription at discharge, post-PCI vascular or bleeding complications, and extended length of stay. Discrimination of the pre-PCI model (C-statistic=0.68) was modestly improved by the addition of post-PCI variables in the Discharge model (C-statistic=0.69; integrated discrimination improvement, 0.009; P<0.001). Conclusions These prediction models can be used to identify patients at high risk for readmission after PCI and to target high-risk patients for interventions to prevent readmission. C1 [Wasfy, Jason H.; Rosenfield, Kenneth; Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA 02115 USA. [Zelevinsky, Katya; Lovett, Ann; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Sakhuja, Rahul] Wellmont CVA Heart Inst, Kingsport, TN USA. [Spertus, John A.] UMKC, St Lukes Mid America Heart Inst, Kansas City, MO USA. [Wimmer, Neil J.; Mauri, Laura] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mauri, Laura; Yeh, Robert W.] Harvard Clin Res Inst, Boston, MA USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843,55 Fruit St, Boston, MA 02114 USA. EM ryeh@partners.org FU Massachusetts Department of Public Health; American Heart Association [12CRP9010016]; Abbott Vascular; Bard Peripheral Vascular; Ownership Interest; Lumen Biomedical; Medical Stimulation Corp; VIVA Physicians Association; Consultant/Advisory Board; Angioguard; Boston Scientific; Complete Conference Manager; Harvard Clinical Research Institute; Abbott; Cordis; Medtronic; Eli Lilly; Daiichi Sankyo; Bristol Myers Squibb; sanofi-aventis; American College of Cardiology Foundation; Equity; Health Outcomes Sciences FX This work was supported in part by the Massachusetts Department of Public Health and a grant from the American Heart Association (12CRP9010016).; Kenneth Rosenfield is a recipient of the following: research grant, Abbott Vascular, <$10 000; Bard Peripheral Vascular, <$10 000; Ownership Interest, Lumen Biomedical, <$10 000; Medical Stimulation Corp, <$10 000; VIVA Physicians Association, >=$10 000; Consultant/Advisory Board, Abbott Vascular, <$10 000; Angioguard, <$10 000; Boston Scientific, <$10 000; Complete Conference Manager, <$10 000; Harvard Clinical Research Institute, <$10 000. Laura Mauri is a recipient of the following: research grant, Abbott, >=$10 000; Boston Scientific, >=$10 000; Cordis, >=$10 000; Medtronic, >=$10 000; Eli Lilly, >=$10 000; Daiichi Sankyo, >=$10 000; Bristol Myers Squibb, >=$10 000; sanofi-aventis, >=$10 000; Consultant/Advisory Board: Cordis, <$10 000; Medtronic, >=$10 000. John Spertus is a recipient of the following: research grant, American College of Cardiology Foundation, >$10 000; Equity, Health Outcomes Sciences, <$10 000. The other authors report no conflicts. NR 13 TC 22 Z9 22 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2013 VL 6 IS 4 BP 429 EP 435 DI 10.1161/CIRCOUTCOMES.111.000093 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 184NM UT WOS:000321898000010 PM 23819957 ER PT J AU Cullen, MW Kim, S Piccini, JP Ansell, JE Fonarow, GC Hylek, EM Singer, DE Mahaffey, KW Kowey, PR Thomas, L Go, AS Lopes, RD Chang, P Peterson, ED Gersh, BJ AF Cullen, Michael W. Kim, Sunghee Piccini, Jonathan P. Ansell, Jack E. Fonarow, Greg C. Hylek, Elaine M. Singer, Daniel E. Mahaffey, Kenneth W. Kowey, Peter R. Thomas, Laine Go, Alan S. Lopes, Renato D. Chang, Paul Peterson, Eric D. Gersh, Bernard J. TI Risks and Benefits of Anticoagulation in Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE anticoagulants; atrial fibrillation; hemorrhage; risk factors; stroke prevention ID NET CLINICAL BENEFIT; ANTITHROMBOTIC THERAPY; STROKE PREVENTION; WARFARIN USE; PREDICTING STROKE; TRIALS TRANSLATE; TRENDS; GUIDELINES; MANAGEMENT; CARE AB Background Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC. Methods and Results We analyzed OAC use among 10098 patients with AF from 174 community-based outpatient practices enrolled in 2010-2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS(2)), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS(2) scores, from 53% for CHADS(2)=0 to 80% for CHADS(2)2 (P<0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA5 (P<0.001). A significant interaction existed between ATRIA and CHADS(2) scores (P=0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS(2) stroke risk had a smaller impact on use of OAC. Conclusions In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk. C1 [Cullen, Michael W.; Gersh, Bernard J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [Kim, Sunghee; Thomas, Laine] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lopes, Renato D.; Peterson, Eric D.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Ansell, Jack E.] Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. [Fonarow, Greg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Hylek, Elaine M.] Boston Univ, Sch Med, Dept Gen Internal Med, Boston, MA 02118 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. [Kowey, Peter R.] Lankenau Hosp, Div Cardiovasc Dis, Wynnewood, PA USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Chang, Paul] Janssen Pharmaceut Inc, New Brunswick, NJ USA. RP Cullen, MW (reprint author), Mayo Clin, Dept Internal Med, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. EM cullen.michael@mayo.edu FU Johnson & Johnson Pharmaceuticals; Boston Scientific; Johnson Johnson; Takeda; Amgen; Medtronic; Novartis; Gambro; National Institutes of Health/National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Adolor; Alexion; Argolyn Bioscience; AstraZeneca; Daiichi; Sankyo; Eli Lilly; Elsevier; Forest Labs; Genentech; GlaxoSmithKline; Guidant; Ikarja; Pfizer; Proctor Gamble; Sanofi Aventis; Schering Plough; Scios; WebMD; Abbott Vascular; Amylin; CardioKinetix; Cierra; Cordis; Edwards LifeSciences; KCI Medical; Luitpold Pharmaceutical; Momenta Pharmaceuticals; Portola Pharmaceutical; Pozen; Regado Biotechnologies; Medicines Company; Bistol-Meyers Squibb; Johnson & Johnson Pharmaceutical Research Development FX This study received financial support from Johnson & Johnson Pharmaceuticals.; The authors report the following conflicts of interest and financial disclosures on this article. Dr Piccini receives research funding from Johnson & Johnson and Boston Scientific. He participates on scientific and advisory boards for Janssen Pharmaceuticals and provides consulting to Forest Laboratories, Medtronic, and Titan Pharmaceuticals. Dr Ansell is a consultant for Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Janssen, and Daiichi. He serves on the Data Safety Monitoring Board of Bristol-Myers Squibb. Dr Fonarow receives consultant fees/honoraria from Takeda, Amgen, Johnson & Johnson, Medtronic, Novartis, and Gambro. He receives research grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, Novartis, and the National Heart, Lung, and Blood Institute. Dr Hylek has served as an advisor to Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, and Pfizer. She has participated in clinical symposia sponsored by Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb. Dr Singer has consulted for Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Merck, Bayer Healthcare, Pfizer, and Sanofi-Aventis. He has received research support from Daiichi Sankyo. Dr Mahaffey has received consulting fees from Adolor, Alexion, Amgen, Argolyn Bioscience, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi, Sankyo, Eli Lilly, Elsevier, Forest Labs, Genentech, GlaxoSmithKline, Guidant, Ikarja, Johnson & Johnson, Merck, Novartis, Pfizer, Proctor & Gamble, Sanofi Aventis, Schering Plough, Scios, and WebMD. He has received grant support from Abbott Vascular, Amgen, Amylin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CardioKinetix, Cierra, Cordis, Edwards LifeSciences, Eli Lilly, Genentech, GlaxoSmithKline, Guidant, Innocoll Pharmaceuticals, Johnson & Johnson, KCI Medical, Luitpold Pharmaceutical, Medtronic, Merck, Momenta Pharmaceuticals, Novartis, Portola Pharmaceutical, Pozen, Regado Biotechnologies, Sanofi Aventis, Schering Plough, and the Medicines Company. He has received lecture fees from Johnson & Johnson. Dr Kowey has served as an advisor or consultant for Sanofi Aventis, Merck, Boehringer Ingelheim Pharmaceuticals, AstraZeneca Pharmaceuticals, and Johnson & Johnson Pharmaceutical Research. He has served as a speaker or a member of a speaker's bureau for Sanofi Aventis, Boehringer Ingelheim Pharmaceuticals, and GlaxoSmithKline. He owns stock, stock options, or bonds from CardioNet. Dr Go has received research support from Johnson & Johnson. Dr Lopes has received research grants from Bistol-Meyers Squibb. He has served as an advisor or consultant for Boehringer Ingelheim Pharmaceuticals, Bristol-Meyers Squibb, and Pfizer. Dr Chang is employed by Johnson & Johnson. Dr Peterson has received research grants from Bristol-Meyers Squibb, Eli Lilly, Johnson & Johnson Pharmaceutical Research & Development, and Sanofi-Aventis. The other authors report no conflicts. NR 35 TC 28 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2013 VL 6 IS 4 BP 461 EP 469 DI 10.1161/CIRCOUTCOMES.113.000127 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 184NM UT WOS:000321898000014 PM 23759473 ER PT J AU Mahaffey, KW Hellkamp, AS Patel, MR Hannan, KL Schwabe, K Nessel, CC Berkowitz, SD Halperin, JL Hankey, GJ Becker, RC Piccini, JP Breithardt, G Hacke, W Singer, DE Califf, RM Fox, KAA AF Mahaffey, Kenneth W. Hellkamp, Anne S. Patel, Manesh R. Hannan, Karen L. Schwabe, Kimberly Nessel, Christopher C. Berkowitz, Scott D. Halperin, Jonathan L. Hankey, Graeme J. Becker, Richard C. Piccini, Jonathan P. Breithardt, Guenter Hacke, Werner Singer, Daniel E. Califf, Robert M. Fox, Keith A. A. TI End of Study Transition From Study Drug to Open-Label Vitamin K Antagonist Therapy: The ROCKET AF Experience SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE atrial fibrillation; bridging; discontinuations; factor Xa; randomized controlled trial; rivaroxaban; stroke ID NONVALVULAR ATRIAL-FIBRILLATION; STROKE PREVENTION; EMBOLISM TRIAL; WARFARIN; RIVAROXABAN; ANTICOAGULATION AB Background To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist. Methods and Results At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42; warfarin 6 events, event rate 1.73; hazard ratio, 3.72; 95% confidence interval, 1.51-9.16; P=0.0044). No INR values were reported for approximate to 5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had 1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group. Conclusions The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation. C1 [Mahaffey, Kenneth W.; Hellkamp, Anne S.; Patel, Manesh R.; Hannan, Karen L.; Becker, Richard C.; Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27705 USA. [Schwabe, Kimberly; Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. [Breithardt, Guenter] Hosp Univ Munster, Dept Cardiol & Angiol, Munster, Germany. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Keith A. A.] Univ Edinburgh, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland. RP Mahaffey, KW (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM kenneth.mahaffey@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ; Bayer HealthCare AG, Leverkusen, Germany; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Eli Lilly; GlaxoSmithKline; Johnson Johnson; Merck; Momenta Pharmaceuticals; Novartis; Portola; Pozen; Regado Biotechnologies; Sanofi-Aventis; Medicines Company; Ortho/ McNeill; Polymedix; Ortho McNeil Janssen; Bayer HealthCare; Genzyme; Boston Scientific; Medtronic; Forest Laboratories; Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital (Boston, MA) FX This work was sponsored by Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ; and Bayer HealthCare AG, Leverkusen, Germany.; K. Mahaffey has disclosed grant support (significant) from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plough (now Merck), and The Medicines Company; significant consulting fees from AstraZeneca and Johnson & Johnson; and modest consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Ortho/ McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plough (now Merck). M. R. Patel has disclosed honoraria from Johnson & Johnson and Bayer HealthCare for serving on the executive committee of the ROCKET AF; consulting fees from Ortho McNeil Janssen and Bayer HealthCare; and advisory board fees from Genzyme. K. Schwabe and C. Nessel are employees of Johnson & Johnson Pharmaceutical Research & Development. S. Berkowitz is an employee of Bayer HealthCare Pharmaceuticals. J. L. Halperin has disclosed honoraria from Johnson & Johnson and Bayer; and advisory board fees from Boehringer Ingelheim, Bristol Myers-Squibb, and Pfizer. G. J. Hankey has disclosed honoraria from Johnson & Johnson, Bayer, and Sanofi-Aventis; and has received fees for serving on trial adjudication committees and an advisory board for Boehringer Ingelheim. R. C. Becker has disclosed research support from Bayer and Johnson & Johnson. J. Piccini has disclosed grants for clinical research from Johnson & Johnson and Boston Scientific; and consulting and advisory board fees from Medtronic, Forest Laboratories, Sanofi-Aventis, and Johnson & Johnson. G. Breithardt has disclosed honoraria from Johnson & Johnson and Bayer; and advisory board fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. W. Hacke has disclosed honoraria from Johnson & Johnson and Bayer; and advisory board fees from Boehringer Ingelheim. D. E. Singer has disclosed support, in part, by the Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital (Boston, MA); consulting fees from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, and Sanofi; and serves as a member of the executive committee of the ROCKET AF of rivaroxaban versus warfarin in patients with AF sponsored by Johnson & Johnson and Bayer HealthCare. R. M. Califf has disclosed consulting fees and research funding from Johnson & Johnson; and all other industry interactions are listed at www. dcri. org. K. Fox has disclosed grants and honoraria from Bayer, Lilly, Boehringer Ingelheim, Sanofi-Aventis, and GlaxoSmithKline. The other authors report no conflicts. NR 11 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2013 VL 6 IS 4 BP 470 EP 478 DI 10.1161/CIRCOUTCOMES.113.000132 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 184NM UT WOS:000321898000015 PM 23759472 ER PT J AU Kramer, DB Kennedy, KF Noseworthy, PA Buxton, AE Josephson, ME Normand, SL Spertus, JA Zimetbaum, PJ Reynolds, MR Mitchell, SL AF Kramer, Daniel B. Kennedy, Kevin F. Noseworthy, Peter A. Buxton, Alfred E. Josephson, Mark E. Normand, Sharon-Lise Spertus, John A. Zimetbaum, Peter J. Reynolds, Matthew R. Mitchell, Susan L. TI Characteristics and Outcomes of Patients Receiving New and Replacement Implantable Cardioverter-Defibrillators: Results From the NCDR SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE death; sudden; defibrillation; implantable cardioverter-defibrillators ID CARDIAC-RESYNCHRONIZATION THERAPY; HEART-FAILURE; RISK SCORE; EJECTION FRACTION; DEVICE ADVISORIES; PROPENSITY-SCORE; EARLY MORTALITY; COMPLICATIONS; REGISTRY; LONGEVITY AB Background Little is known about the clinical features, procedural risks, or survival of patients receiving replacement versus new implantable cardioverter-defibrillators (ICDs). Methods and Results Entries in the National Cardiovascular Data Registry (NCDR) ICD Registry from 2005 through 2010 were eligible for inclusion (n=463978). Baseline demographic data, clinical information, and procedural variables were compared between patients receiving new (n=359993; 77.6%) and replacement (n=103985; 22.4%) ICDs and entered into a propensity match model to determine adjusted survival rates. Patients receiving replacement ICDs were older (70.7 versus 67.5 years of age) and more likely to have atrial fibrillation (41.8% versus 31.4%; P<0.001) and ventricular tachycardia (60.5% versus 33.9%; P<0.001) compared with patients receiving new ICDs. Median battery life was only 4.6 years (25%-75% interquartile range, 3.7-5.8) for all replaced devices, 5.8 (25%-75% interquartile range, 4.2-7.5) for single-chamber, 5.1 (25%-75% interquartile range, 4.1-6.1) for dual-chamber, and 3.9 (25%-75% interquartile range, 3.2-4.6) years for biventricular devices. Patients receiving replacement ICDs had lower rates of index admission complications (0.9% versus 3.2%; P<0.001) but greater risk for death compared receiving patients receiving new ICDs in unadjusted analysis (hazard ratio, 1.18; 95% confidence interval, 1.16-1.20; P<0.0001) and after propensity-score matching (hazard ratio, 1.28; 95% confidence interval, 1.25-1.30; P<0.0001). Conclusions Patients receiving replacement ICDs are older and at greater risk for death compared with those receiving initial ICD implants. The battery life of initial ICDs is shorter than previously reported. C1 [Kramer, Daniel B.; Buxton, Alfred E.; Josephson, Mark E.; Zimetbaum, Peter J.; Reynolds, Matthew R.; Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kramer, Daniel B.; Noseworthy, Peter A.; Buxton, Alfred E.; Josephson, Mark E.; Normand, Sharon-Lise; Zimetbaum, Peter J.; Reynolds, Matthew R.; Mitchell, Susan L.] Harvard Univ, Sch Med, Boston, MA USA. [Kennedy, Kevin F.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Noseworthy, Peter A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kramer, Daniel B.; Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Mitchell, Susan L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Kramer, DB (reprint author), 1200 Ctr St, Boston, MA 02215 USA. EM danielkramer@hsl.harvard.edu FU NCDR of the American College of Cardiology Foundation; John A. Hartford Foundation; Harvard Clinical and Translational Science Center; National Institutes of Health-National Institute on Aging [K24AG033640]; American College of Cardiology Foundation FX This research was supported by the NCDR of the American College of Cardiology Foundation.; The views expressed in this article represent those of the author(s) and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. ICD Registry is an initiative of the American College of Cardiology Foundation and the Heart Rhythm Society. Dr Kramer is the Lois Green Scholar at the Hebrew SeniorLife Institute for Aging Research and is additionally supported by an award from the John A. Hartford Foundation and a career development award from the Harvard Clinical and Translational Science Center. 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, or the National Institutes of Health. Dr Mitchell is supported by National Institutes of Health-National Institute on Aging K24AG033640. J.A. Spertus reports a contract from the American College of Cardiology Foundation to provide analytic support for the NCDR. A. E. Buxton reports honoraria from St. Jude Medical for serving on DSMB for a clinical trial (unrelated to ICDs), honoraria from Medtronic for speaking at educational symposia and serving on Events Committee for a clinical trial (not related to ICDs), honoraria from Boston Scientific for serving on Events Committee for a clinical trial (not related to ICDs), and is a GE Healthcare consultant (for imaging, nothing related to ICDs). M.E. Josephson reports honoraria from Medtronic for educational courses and small advisory input and honoraria from Biotronik for educational courses. M.R. Reynolds reports consulting contract with Medtronic. The other authors report no conflicts. NR 26 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2013 VL 6 IS 4 BP 488 EP 497 DI 10.1161/CIRCOUTCOMES.111.000054 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 184NM UT WOS:000321898000017 PM 23759471 ER PT J AU Celano, CM Suarez, L Mastromauro, C Januzzi, JL Huffman, JC AF Celano, Christopher M. Suarez, Laura Mastromauro, Carol Januzzi, James L. Huffman, Jeff C. TI Feasibility and Utility of Screening for Depression and Anxiety Disorders in Patients With Cardiovascular Disease SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE anxiety; cardiovascular disease; depression; screening ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; PRIMARY-CARE; COLLABORATIVE CARE; RANDOMIZED-TRIAL; CARDIAC EVENTS; MANAGEMENT PROGRAM; MENTAL-DISORDERS; ARTERY-DISEASE; RISK-FACTOR AB Background Depression and anxiety in patients with cardiac disease are common and independently associated with morbidity and mortality. We aimed to explore the use of a 3-step approach to identify inpatients with cardiac disease with depression, generalized anxiety disorder (GAD), or panic disorder; understand the predictive value of individual screening items in identifying these disorders; and assess the relative prevalence of these disorders in this cohort. Methods and Results To identify depression and anxiety disorders in inpatients with cardiac disease as part of a care management trial, an iterative 3-step screening procedure was used. This included an existing 4-item (Coping Screen) tool in nursing data sets, a 5-item screen for positive Coping Screen patients (Patient Health Questionnaire-2 [PHQ-2], GAD-2, and an item about panic attacks), and a diagnostic evaluation using PHQ-9 and the Primary Care Evaluation of Mental Disorders anxiety disorder modules. Overall, 6210 inpatients received the Coping Screen, 581 completed portions of all 3 evaluation steps, and 210 received a diagnosis (143 depression, 129 GAD, 30 panic disorder). Controlling for age, sex, and the other screening items, PHQ-2 items independently predicted depression (little interest/pleasure: odds ratio [OR]=6.65, P<0.001; depression: OR=5.24, P=0.001), GAD-2 items predicted GAD (anxious: OR=4.09, P=0.003; unable to control worrying: OR=10.46, P<0.001), and the panic item predicted panic disorder (OR=49.61, P<0.001). Conclusions GAD was nearly as prevalent as depression in this cohort, and GAD-2 was an effective screening tool; however, panic disorder was rare. These results support the use of 2-step screening for depression and GAD beginning with a 4-item scale (GAD-2 plus PHQ-2). Clinical Trial Registration Unique Identifier: NCT01201967. URL: . C1 [Celano, Christopher M.; Januzzi, James L.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Celano, Christopher M.; Suarez, Laura; Mastromauro, Carol; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Celano, CM (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM ccelano@partners.org FU American Heart Association [10GRNT3450015] FX J. Huffman was a recipient of American Heart Association Grant-in-Aid 10GRNT3450015. The other authors report no conflicts. NR 31 TC 16 Z9 16 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2013 VL 6 IS 4 BP 498 EP 504 DI 10.1161/CIRCOUTCOMES.111.000049 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 184NM UT WOS:000321898000018 PM 23759474 ER PT J AU Fett, N AF Fett, Nicole TI Scleroderma: Nomenclature, etiology, pathogenesis, prognosis, and treatments: Facts and controversies SO CLINICS IN DERMATOLOGY LA English DT Article ID PULMONARY ARTERIAL-HYPERTENSION; JUVENILE LOCALIZED SCLERODERMA; PUVA BATH PHOTOCHEMOTHERAPY; LOW-DOSE METHOTREXATE; 1ST CASE SERIES; SYSTEMIC-SCLEROSIS; MYCOPHENOLATE-MOFETIL; LINEAR SCLERODERMA; UVA1 PHOTOTHERAPY; PLAQUE MORPHEA AB Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options. Published by Elsevier Inc. C1 [Fett, Nicole] Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Fett, Nicole] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Fett, N (reprint author), Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA. EM nmfett325@gmail.com NR 93 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 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JUL-AUG PY 2013 VL 31 IS 4 BP 432 EP 437 DI 10.1016/j.clindermatol.2013.01.010 PG 6 WC Dermatology SC Dermatology GA 181QR UT WOS:000321684100011 PM 23806160 ER PT J AU Tapias, LF Mino-Kenudson, M Lee, H Wright, C Gaissert, HA Wain, JC Mathisen, DJ Lanuti, M AF Tapias, Luis F. Mino-Kenudson, Mari Lee, Hang Wright, Cameron Gaissert, Henning A. Wain, John C. Mathisen, Douglas J. Lanuti, Michael TI Risk factor analysis for the recurrence of resected solitary fibrous tumours of the pleura: a 33-year experience and proposal for a scoring system SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article; Proceedings Paper CT 20th European Conference on General Thoracic Surgery CY JUN 10-13, 2012 CL Essen, GERMANY DE Solitary fibrous tumour; Pleura; Recurrence ID SURGICAL-TREATMENT; EXPRESSION AB OBJECTIVES: Surveillance after resection of solitary fibrous tumours of the pleura (SFTP) remains undefined. This study reviews our experience with surgical treatment of SFTP to determine the specific risk factors to predict recurrence. METHODS: A retrospective review of 59 patients surgically treated for SFTP during the years 1977-2010 was conducted. Clinico-pathological factors for recurrence were analysed by Kaplan-Meier and Cox proportional hazard methods. RESULTS: The mean age was 57 +/- 14 years. There were 32 (54%) men. Among 32 (54%) symptomatic patients, chest pain (22%), cough (19%) and dyspnoea (17%) were most frequent. The mean tumour size was 7.3 +/- 6.7 cm, and 14 patients had SFTPs larger than 10 cm. An SFTP was pedunculated in 38 (67%) cases and had a visceral origin in 40 (68%). Paraneoplastic syndromes were observed in 3 (5%) patients. On histopathologic analysis, 4 (7%) presented >= 4 mitosis/10 high-power fields (HPFs), 8 (15%) atypia, 14 (24%) hypercellularity and 6 (10%) necrosis. After a mean follow-up of 8.8 +/- 7.0 years, we observed 8 (14%) recurrences; median time to recurrence was 6 years (range 2-16 years). Two (3%) patients received adjuvant therapy. We constructed a predictive score for recurrence by assigning one point to each of the six variables: parietal (vs visceral) pleural origin, sessile (vs pedunculated) morphology, size >10 cm (vs <10 cm), the presence of hypercellularity, necrosis and mitotic activity >= 4/HPF (vs <4). A score of >= 3 best predicted recurrence (sensitivity: 100%, specificity: 92%, area under receiver operating characteristic curve = 0.966, P < 0.0001). With a score of = 3, recurrence-free survival was 80%, 69, 23 and 23% at 3, 5, 10 and 15 years, whereas a score of < 3 was 100% up to 15 years. Our scoring system was superior in predicting malignant behaviour and recurrence compared with England's criteria or de Perrot staging. CONCLUSIONS: The proposed scoring system is simple, easily obtained from existing pathological description and reliably predicts recurrence in this patient population harbouring SFTP. The SFTP score may stratify patient risk and guide postoperative surveillance. We recommend validation in additional clinical series. C1 [Tapias, Luis F.; Wright, Cameron; Gaissert, Henning A.; Wain, John C.; Mathisen, Douglas J.; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@partners.org FU NCATS NIH HHS [8UL1TR000170-05] NR 15 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD JUL PY 2013 VL 44 IS 1 BP 111 EP 117 DI 10.1093/ejcts/ezs629 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 183OQ UT WOS:000321826700035 PM 23233072 ER PT J AU Harte, CB Meston, CM AF Harte, C. B. Meston, C. M. TI Association between cigarette smoking and erectile tumescence: the mediating role of heart rate variability SO INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH LA English DT Article DE erectile function; heart rate variability; mediation; penile hemodynamics; smoking; smoking cessation ID SPECTRAL-ANALYSIS; NERVOUS-SYSTEM; SEXUAL AROUSAL; BLOOD-PRESSURE; DOUBLE-BLIND; CESSATION; NICOTINE; DYSFUNCTION; MEN; DISORDERS AB Cigarette smoking deleteriously affects erectile function, and conversely, quitting smoking improves erectile hemodynamics. Underlying mechanisms by which smoking (or reduction of smoking frequency) may affect erectile physiology are not well understood. This study examined the mediating role of heart rate variability (HRV; a marker of sympathovagal balance) among a sample of male chronic smokers from the United States. Sixty-two healthy men (M-age = 38.27 years; s.d. = 10.62) were assessed at baseline (while smoking regularly), at mid-treatment (while using a nicotine patch) and at follow-up, 4 weeks after patch discontinuation. Cigarette use, frequency-domain parameters of HRV (low frequency (LF), high frequency (HF), LF/HF ratio) and physiological sexual arousal responses (via penile plethysmography) were assessed at each visit. Results were consistent with mediation, in that greater reductions in cigarette use from baseline to follow-up were associated with longitudinal increases in LF, which in turn showed positive relationships with across-time changes in erectile tumescence. Neither HF nor LF/HF ratio mediated the relationship between smoking and erection. In conclusion, HRV mediated the inverse relationship between reductions in smoking and enhancements in erectile tumescence. Results underscore the possibility that cigarette use may deleteriously affect erectile function peripherally, in part, by disrupting cardiac autonomic function. C1 [Harte, C. B.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Harte, C. B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Meston, C. M.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. RP Harte, CB (reprint author), VA Boston Healthcare Syst, Res Serv, 150 South Huntington Ave 116-B4, Boston, MA 02130 USA. EM christopher.harte@va.gov FU National Institute on Drug Abuse (NIDA) [F31DA026276]; National Institute of Child Health and Human Development (NICHD) [1 RO1 HD051676-01 A1]; Sexual Medicine Society of North America Student Research Grant; University of Texas at Austin; American Psychological Association Dissertation Research Award; Kinsey Institute Student Research Grant FX This project was supported by Award Number F31DA026276 from the National Institute on Drug Abuse (NIDA) to Christopher Harte. The contents of this work are solely the responsibility of the author and do not necessarily represent the official views of the NIDA or the National Institutes of Health. Portions of this work were also made possible by Grant Number 1 RO1 HD051676-01 A1 to Cindy M Meston from the National Institute of Child Health and Human Development (NICHD). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NICHD. This project was also supported by the following fellowships/awards to the first author: The Sexual Medicine Society of North America Student Research Grant; two Graduate Dean's Prestigious Fellowship Supplements, and a College of Liberal Arts Graduate Research Fellowship, all from the University of Texas at Austin; the American Psychological Association Dissertation Research Award; and The Kinsey Institute Student Research Grant. We thank Tyler Watts, Hillary Perlman, Olivia Bentkowski, Alicia Whitaker, Gail Dalton and Katy Siciliano for help with participant recruitment, screening and data management. NR 40 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0955-9930 J9 INT J IMPOT RES JI Int. J. Impot. Res. PD JUL-AUG PY 2013 VL 25 IS 4 BP 155 EP 159 DI 10.1038/ijir.2012.43 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 183LC UT WOS:000321815200007 PM 23303335 ER PT J AU Teitelman, AM Tennille, J Bohinski, J Jemmott, LS Jemmott, JB AF Teitelman, Anne M. Tennille, Julie Bohinski, Julia Jemmott, Loretta S. Jemmott, John B., III TI Urban Adolescent Girls' Perspectives on Multiple Partners in the Context of the Sexual Double Standard and Intimate Partner Violence SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE adolescent; females; HIV; multiple sexual partners; partner abuse; safer sex ID GENDER-BASED VIOLENCE; DATING VIOLENCE; RELATIONSHIP POWER; RISK BEHAVIOR; HIV; PERPETRATION; PREGNANCY; HEALTH; WOMEN; TRIAL AB This article describes the influence of abusive and nonabusive relationship dynamics on the number of sex partners among urban adolescent girls. Focus groups were conducted with 64 sexually active adolescent girls ages 14 to 17 years. General coding and content analyses identified patterns, themes, and salient beliefs. More than one third (37.5%) reported having experienced physical, intimate partner violence; 32.8% had two or more recent sex partners, and 37.5% had ever had a sexually transmitted infection (STI) or HIV. Although some girls in abusive relationships feared retribution if they had more than one partner, others sought additional partners for solace or as an act of resistance. Adolescent HIV/STI prevention programs need to address the influence of gender norms such as the sexual double standard, as well as partner pressure and partner abuse on adolescent decision-making about safer sex, and also promote healthy relationships as integral to advancing HIV/STI risk reduction. Copyright (C) 2013 Association of Nurses in AIDS Care C1 [Teitelman, Anne M.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Tennille, Julie] W Chester Univ, Grad Sch Social Work, W Chester, PA 19380 USA. [Bohinski, Julia] Optimal Stategix Grp Inc, Philadelphia, PA USA. [Jemmott, Loretta S.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Jemmott, John B., III] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Jemmott, John B., III] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. RP Teitelman, AM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. FU National Institute of Mental Health [1K01MH080649-01A1]; University of Pennsylvania: Center for AIDS Research and Institute for Urban Research FX This research was supported by National Institute of Mental Health grant 1K01MH080649-01A1 and the University of Pennsylvania: Center for AIDS Research and Institute for Urban Research. The authors would like to express appreciation to the late Dr. Martin Fishbein for suggestions about the wording of the open-ended questions on the brief survey; Dr. Patricia Benner, Dr. Pat D'Antonio, and Annet Davis-Vogel for reading and commenting on drafts of the paper; Lynette Gueits for her role in advising on the development of the focus group guide; The Talking about Relationships Project research team members for logistical support during focus groups and for insightful discussions during the coding process; and the research study participants for the time and thoughtful comments they provided. NR 31 TC 2 Z9 2 U1 3 U2 38 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 EI 1552-6917 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD JUL-AUG PY 2013 VL 24 IS 4 SI SI BP 308 EP 321 DI 10.1016/j.jana.2013.04.001 PG 14 WC Nursing SC Nursing GA 184AP UT WOS:000321859000004 PM 23790274 ER PT J AU Tseng, J Halperin, L Ritholz, MD Hsu, WC AF Tseng, Juliana Halperin, Lucila Ritholz, Marilyn D. Hsu, William C. TI Perceptions and management of psychosocial factors affecting type 2 diabetes mellitus in Chinese Americans SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Cultural competency; Chinese Americans; Cross-cultural care; Diversity ID HEALTH-CARE ACCESS; ASIAN-AMERICANS; CULTURAL COMPETENCE; PACIFIC ISLANDERS; NATIVE HAWAIIANS; CONTROLLED-TRIAL; SELF-MANAGEMENT; MEDICINE; ACCULTURATION; QUALITY AB Diabetes has become a global pandemic and Chinese Americans are at least 60% more likely to develop type 2 diabetes than White Americans, despite having lower body weight, due to a combination of genetic and environmental factors. Because of the increased risk, it is vitally important to address the issues of treatment adherence and diabetes self-management in the Chinese American population. Many factors affect an individual's ability to manage diabetes, including cultural beliefs, immigration experience, language abilities/health literacy, educational background, employment, and accessibility of healthcare services. In treating Chinese American patients, these factors must be considered to determine appropriate treatment. Eastern cultural and individual beliefs differ greatly from Western beliefs and, therefore, may affect the presentation of the patients. If left unacknowledged, these differences might be misinterpreted by healthcare providers as merely treatment non-adherence or unwillingness to change. Suggestions for providing culturally competent healthcare are discussed. (C) 2013 Elsevier Inc. All rights reserved. C1 [Tseng, Juliana] Massachusetts Sch Profess Psychol, Maastricht, Netherlands. [Ritholz, Marilyn D.; Hsu, William C.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Hsu, WC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM William.Hsu@Joslin.Harvard.edu NR 73 TC 6 Z9 6 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL-AUG PY 2013 VL 27 IS 4 BP 383 EP 390 DI 10.1016/j.jdiacomp.2013.01.001 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181OZ UT WOS:000321679700017 PM 23545465 ER PT J AU Fargen, KM Frei, D Fiorella, D McDougall, CG Myers, PM Hirsch, JA Mocco, J AF Fargen, Kyle M. Frei, Donald Fiorella, David McDougall, Cameron G. Myers, Philip M. Hirsch, Joshua A. Mocco, J. TI The FDA approval process for medical devices: an inherently flawed system or a valuable pathway for innovation? SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID INTRACRANIAL ARTERIAL-STENOSIS; MATCHED-PAIR ANALYSIS; BARE PLATINUM COILS; CERECYTE COILS; ANEURYSMS; REVASCULARIZATION; THERAPY; DISEASE; SAFETY C1 [Fargen, Kyle M.] Univ Florida, Dept Neurosurg, Gainesville, FL USA. [Frei, Donald] Radiol Imaging Associates, Dept Intervent Neuroradiol, Englewood, CO USA. [Fiorella, David] SUNY Stony Brook, Dept Neurol Surg, Stony Brook, NY 11794 USA. [McDougall, Cameron G.] Barrow Neurol Inst, Dept Neurol Surg, Phoenix, AZ 85013 USA. [Myers, Philip M.] Columbia Univ, Dept Neurosurg, New York, NY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Mocco, J.] Vanderbilt Univ, Dept Neurosurg, Nashville, TN 37235 USA. RP Fargen, KM (reprint author), Box 100265, Gainesville, FL 32610 USA. EM kyle.fargen@neurosurgery.ufl.edu NR 34 TC 8 Z9 8 U1 2 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 269 EP 275 DI 10.1136/neurintsurg-2012-010400 PG 7 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500001 PM 22764203 ER PT J AU Leslie-Mazwi, TM AF Leslie-Mazwi, Thabele M. TI Antiplatelet testing in neurointervention: we cannot ignore the signs SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID PLATELET REACTIVITY; CLOPIDOGREL; PRASUGREL; INHIBITION; RESISTANCE; ASPIRIN; STROKE; TRIAL C1 Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. RP Leslie-Mazwi, TM (reprint author), Massachusetts Gen Hosp, Neuroendovasc Program, 55 Fruit St,GRB 2-241, Boston, MA 02114 USA. EM tleslie-mazwi@mgh.harvard.edu NR 21 TC 4 Z9 4 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 277 EP 279 DI 10.1136/neurintsurg-2013-010809 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500003 PM 23761594 ER PT J AU Patsalides, A Bulsara, KR Hsu, DP Abruzzo, T Narayanan, S Jayaraman, MV Duckwiler, G Klucznik, RP Kelly, M Hirsch, JA Heck, D Sunshine, J Frei, D Alexander, MJ Do, HM Meyers, PM AF Patsalides, Athos Bulsara, Ketan R. Hsu, Daniel P. Abruzzo, Todd Narayanan, Sandra Jayaraman, Mahesh V. Duckwiler, Gary Klucznik, Richard Paul Kelly, Michael Hirsch, Joshua A. Heck, Don Sunshine, Jeffery Frei, Don Alexander, Michael J. Do, Huy M. Meyers, Philip M. TI Standard of practice: embolization of ruptured and unruptured intracranial aneurysms SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Reprint ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; CEREBRAL ANEURYSMS; ENDOVASCULAR TREATMENT; MR-ANGIOGRAPHY; FOLLOW-UP; COIL EMBOLIZATION; RANDOMIZED-TRIAL; NATURAL-HISTORY; OUTCOMES; INTERVENTION C1 [Patsalides, Athos] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Neurol Surg, New York, NY 10065 USA. [Bulsara, Ketan R.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Hsu, Daniel P.] Univ Hosp Cleveland, Case Med Ctr, Dept Intervent Neuroradiol, Cleveland, OH 44106 USA. [Abruzzo, Todd] Univ Cincinnati, Dept Neurosurg, Cincinnati, OH USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Jayaraman, Mahesh V.] Brown Univ, Warren Alpert Sch Med, Dept Diagnost Imaging, Providence, RI 02912 USA. [Jayaraman, Mahesh V.] Brown Univ, Warren Alpert Sch Med, Dept Neurosurg, Providence, RI 02912 USA. [Duckwiler, Gary] Univ Calif Los Angeles, Med Ctr, Dept Radiol Sci, Los Angeles, CA 90024 USA. [Klucznik, Richard Paul] Methodist Hosp, Dept Neuroradiol, Houston, TX 77030 USA. [Kelly, Michael] Univ Saskatchewan, Royal Univ Hosp, Dept Neurosurg, Saskatoon, SK, Canada. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Heck, Don] Forsyth Med Ctr, Dept Radiol, Winston Salem, NC USA. [Sunshine, Jeffery] Univ Hosp Cleveland, Dept Radiol, Case Med Ctr, Cleveland, OH 44106 USA. [Frei, Don] Radiol Imaging Associates, Dept Intervent Neuroradiol, Englewood, CO USA. [Alexander, Michael J.] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Do, Huy M.] Stanford Univ, Med Ctr, Dept Radiol & Neurosurg, Stanford, CA 94305 USA. [Meyers, Philip M.] Columbia Univ, Dept Radiol & Neurol Surg, New York, NY USA. RP Patsalides, A (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Neurol Surg, 525 East 68th St,Box 99, New York, NY 10065 USA. EM atp9002@med.cornell.edu OI Alexander, Michael/0000-0003-0280-809X NR 42 TC 3 Z9 3 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 283 EP 288 DI 10.1136/neurintsurg-2012-010645 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500005 PM 23576604 ER PT J AU Nogueira, RG Yoo, AJ Masrur, S Batista, LM Hakimelahi, R Hirsch, JA Schwamm, LH AF Nogueira, Raul G. Yoo, Albert J. Masrur, Shihab Batista, Leonardo M. Hakimelahi, Reza Hirsch, Joshua A. Schwamm, Lee H. TI Safety of full-dose intravenous recombinant tissue plasminogen activator followed by multimodal endovascular therapy for acute ischemic stroke SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID INTRAARTERIAL THROMBOLYSIS; INTERVENTIONAL MANAGEMENT; RECANALIZATION; TRIAL AB Background and purpose The optimal management of stroke patients who fail treatment with intravenous recombinant tissue plasminogen activator (rt-PA) remains unknown. A study was undertaken to establish whether treatment with a standard intravenous t-PA dose (0.9 mg/kg) followed by multimodal endovascular therapy would have a similar safety profile to reduced dose (0.6 mg/kg) bridging therapy. Methods A retrospective analysis was performed of a prospectively collected database. All patients treated with full-dose t-PA and endovascular therapy were included. The primary safety endpoints included ECASS-III symptomatic intracranial hemorrhage (sICH) and ECASS parenchymal hematomas (PH). Secondary safety endpoints included severe systemic bleeding and 90-day mortality. Clinical efficacy endpoints included rates of recanalization (TICI 2-3), ambulation at hospital discharge and 90-day independent outcomes (mRS 0-2). Results 106 consecutive patients (mean age 69 +/- 17 years; mean baseline NIH Stroke Scale 17.8 +/- 4.8; 55% women; occlusion sites: MCA-M1 60.4%; MCA-M2 6.6%; ICA-T 19.8%; tandem cervical ICA+MCA-M1 7.5%; basilar artery 5.7%) were identified over a 10-year period. The sICH rate was 8.5% and the PH-1, PH-2 and subarachnoid hemorrhage rates were 2.8%, 8.5% and 2.8%, respectively. There were two (1.9%) severe groin hematomas. The recanalization rate was 66%. At hospital discharge, 41.4% of the patients were ambulatory. The rate of independent functional outcomes at 90 days was 24%; however, this sample is biased since nearly all deaths were captured but detailed 90-day functional outcomes were missing in 27 patients. The 90-day death rate was 32.4%. Conclusion Combined treatment with full-dose intravenous rt-PA followed by multimodal endovascular therapy seems to be associated with similar rates of sICH to that of bridging therapy with reduced rt-PA dosage. C1 [Nogueira, Raul G.; Masrur, Shihab; Batista, Leonardo M.; Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurosurg, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Radiol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Yoo, Albert J.; Hakimelahi, Reza; Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Nogueira, RG (reprint author), Emory Fac Off Bldg,80 Jesse Hill Dr SE,Room 398, Atlanta, GA 30303 USA. EM rnoguei@emory.edu OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS; Penumbra Inc. FX Genentech provides drug supply to the Massachusetts General Hospital at no charge for an NINDS funded clinical trial in the SPOTRIAS network.; RGN: Consultant/Scientific Advisory Board for Concentric Medical, ev3 Neurovascular, CoAxia and Rapid Medical. AJY: Research grant from Penumbra Inc. LHS: Consultant/Scientific Advisory Board for CoAxia and Stroke Systems Consultant to the Massachusetts Department of Public Health. JAH: Equity interest: IntraTech. SM, LMB, RH: none. NR 15 TC 8 Z9 8 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 298 EP 301 DI 10.1136/neurintsurg-2012-010376 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500008 PM 22705875 ER PT J AU Rabinov, JD Yoo, AJ Ogilvy, CS Carter, BS Hirsch, JA AF Rabinov, James David Yoo, Albert J. Ogilvy, Christopher S. Carter, Bob S. Hirsch, Joshua A. TI ONYX versus n-BCA for embolization of cranial dural arteriovenous fistulas SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID VENOUS DRAINAGE; TRANSARTERIAL EMBOLIZATION; MALFORMATIONS; CLASSIFICATION; MANAGEMENT; SHUNTS; SWINE AB Purpose To evaluate the efficacy of n-butyl-2-cyanoacrylate (Trufill n-BCA) versus ethylene vinyl alcohol copolymer (ONYX) for the embolization of cranial dural arteriovenous fistulas (DAVF). Methods Fifty-three consecutive patients with cranial dural AVF were treated with liquid embolic agents from November, 2003 to November, 2008. These 53 patients had 56 lesions treated with arterial embolization. Patients embolized to completion underwent follow-up angiography at 3 months to assess for durable occlusion. Results Twenty-one lesions were treated with n-BCA. Seven patients treated with n-BCA had initial angiographic occlusion of their DAVF, which were durable at 3 months. Six patients had adjunctive treatment with coils and/or polyvinyl alcohol particles, but none of these were occluded by endovascular treatment alone. Eleven patients underwent post-embolization surgery for closure of their DAVF. There was one death related to intractable status epilepticus at presentation. One patient developed a major stroke from venous sinus thrombosis after embolization. Thirty-five lesions were treated with ONYX in 34 patients. Twenty-nine patients treated with ONYX had initial angiographic occlusion of their DAVF by embolization alone. One patient had recurrence at 3 months and was re-treated out of 27 total follow-ups. Four patients underwent post-embolization surgical obliteration of their lesions. No deaths or major strokes occurred in this cohort. Conclusion Initial angiographic occlusion (p=0.0004) and durable angiographic occlusion (p=0.0018) rates for embolization of cranial DAVF show a statistically significant higher efficacy with ONYX compared with n-BCA. Patients embolized with ONYX underwent surgery less frequently compared with those treated with n-BCA (p=0.0015). C1 [Rabinov, James David; Yoo, Albert J.; Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol, Boston, MA USA. [Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Carter, Bob S.] Univ Calif San Diego, Dept Neurosurg, San Diego, CA 92103 USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol Gray241, 55 Fruit St, Boston, MA 02114 USA. EM jrabinov@partners.org NR 22 TC 17 Z9 17 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 306 EP 310 DI 10.1136/neurintsurg-2011-010237 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500010 PM 22550096 ER PT J AU Leslie-Mazwi, TM Chandra, RV Yoo, AJ Rabinov, JD Hirsch, JA AF Leslie-Mazwi, Thabele M. Chandra, Ronil V. Yoo, Albert J. Rabinov, James D. Hirsch, Joshua A. TI Hemorrhagic complications with prasugrel therapy for vascular neurointerventional procedures SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID CLINICAL-IMPLICATIONS; ANTIPLATELET THERAPY; CLOPIDOGREL; RESPONSIVENESS; METAANALYSIS; MANAGEMENT; EVENTS C1 [Leslie-Mazwi, Thabele M.; Chandra, Ronil V.; Yoo, Albert J.; Rabinov, James D.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, Boston, MA 02114 USA. RP Leslie-Mazwi, TM (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, GRB2-241,55 Fruit St, Boston, MA 02114 USA. EM tleslie-mazwi@mgh.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 344 EP 345 DI 10.1136/neurintsurg-2012-010406 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500017 PM 22679132 ER PT J AU Hirsch, JA Rosman, DA Liu, RW Ding, A Manchikanti, L AF Hirsch, Joshua A. Rosman, David A. Liu, Raymond W. Ding, Alexander Manchikanti, Laxmaiah TI Sustainable growth rate 2013: time for definitive intervention SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID PHYSICIAN-PAYMENT OUTLOOK; PRIMER AB Federal healthcare spending has been a subject of intense concern as the US Congress continues to search for ways to reduce the budget deficit. The Congressional Budget Office (CBO) estimated that, even though it is growing more slowly than previously projected, federal spending on Medicare, Medicaid and the State Children's Health Insurance Program (SCHIP) will reach nearly $900 billion in 2013. In 2011 the Medicare program paid $68 billion for physicians and other health professional services, 12% of total Medicare spending. Since 2002 the sustainable growth rate (SGR) correction has called for reductions to physician reimbursements; however, Congress has typically staved off these reductions, although the situation remains precarious for physicians who accept Medicare. The fiscal cliff agreement that came into focus at the end of 2012 averted a 26.5% reduction to physician reimbursements related to the SOB correction. Nonetheless, the threat of these devastating cuts continues to loom. The Administration, Congress and others have devised many options to fix this unsustainable situation. This review explores the historical development of the SGR, touches on elements of the formula itself and outlines current proposals for fixing the SOB problem. A recent CBO estimate reduces the potential cost of a 10-year fix of SGR system to $138 billion. This has provided new hope for resolution of this long-standing issue. C1 [Hirsch, Joshua A.; Rosman, David A.; Liu, Raymond W.; Ding, Alexander; Manchikanti, Laxmaiah] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02214 USA. RP Hirsch, JA (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02214 USA. EM hirsch@snisonline.org NR 26 TC 13 Z9 13 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUL PY 2013 VL 5 IS 4 BP 382 EP 386 DI 10.1136/neurintsurg-2013-010776 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 168YS UT WOS:000320744500025 PM 23645571 ER PT J AU Maguen, S Madden, E Lau, KM Seal, KH AF Maguen, Shira Madden, Erin Lau, Karen M. Seal, Karen H. TI Service Utilization among Iraq and Afghanistan Veterans Screening Positive for Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE brain injuries; health services; mental health; post-traumatic; stress disorders; veterans ID MULTICENTER ANALYSIS; PRIMARY-CARE; AUDIT-C; MANAGEMENT; SYMPTOMS; ETIOLOGY; VALIDITY AB We compared mental health outpatient, primary care, and emergency care service utilization among veterans screening TBI positive (S-TBI+) versus those screening TBI negative (S-TBI-) and describe associations between TBI-related symptoms and health service utilization. Our study population consisted of 1746 Iraq and Afghanistan veterans in VA care screened for TBI between April 1, 2007 and June 1, 2010. Rates of mental health outpatient, primary care, and emergency services utilization were greater for S-TBI+ veterans, compared with S-TBI- veterans, even after adjusting for mental health screen results. Irritability on the initial TBI screen was associated with increased mental health outpatient utilization rates [incidence rate ratio (IRR), 1.64; 95% confidence interval (CI), 1.18-2.3; p < 0.01]. Reports of dizziness (IRR, 1.24; 95% CI, 1.02-1.51; p < 0.05) and headaches (IRR, 1.41; 95% CI, 1.16-1.7; p < 0.001) were associated with increased primary care utilization rates. Higher utilization rates among veterans who screened positive for TBI were not better explained by screening positive for comorbid mental health problems. Knowing that certain symptoms are more strongly associated with increased utilization in certain health service domains will help to better plan for the care of returning veterans who screen positive for TBI. C1 [Maguen, Shira; Madden, Erin; Lau, Karen M.; Seal, Karen H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Maguen, Shira; Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116-P, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov FU Department of Defense Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program; VA Health Sciences Research and Development (HSR&D) Career Development Award FX This research was supported by the Department of Defense Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program (to S.M.) and a VA Health Sciences Research and Development (HSR&D) Career Development Award (to S.M.). The authors thank Gary Abrams, Tatjana Agopian-Novokovic, Daniel Bertenthal, Jeane Bosch, Julie Dinh, Don Donati, Thomas Neylan, and Richard Pham for their contributions. NR 28 TC 1 Z9 1 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2013 VL 30 IS 13 BP 1123 EP 1128 DI 10.1089/neu.2012.2744 PG 6 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 174WB UT WOS:000321186400003 PM 23327186 ER PT J AU Nguyen, HQ Donesky, D Reinke, LF Wolpin, S Chyall, L Benditt, JO Paul, SM Carrieri-Kohlman, V AF Nguyen, Huong Q. Donesky, DorAnne Reinke, Lynn F. Wolpin, Seth Chyall, Lawrence Benditt, Joshua O. Paul, Steven M. Carrieri-Kohlman, Virginia TI Internet-Based Dyspnea Self-Management Support for Patients With Chronic Obstructive Pulmonary Disease SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Self-management; self-care; dyspnea; pulmonary disease; COPD; chronic disease; health behavior; health education; Internet; smartphone; cell phone ID CHRONIC RESPIRATORY QUESTIONNAIRE; QUALITY-OF-LIFE; CONTROLLED-TRIAL; PRIMARY-CARE; REHABILITATION; STATEMENT; COPD; MECHANISMS; PROGRAM AB Context. People with chronic obstructive pulmonary disease experience dyspnea with activities despite optimal medical management. Objectives. The purpose of this study was to test the efficacy of two 12-month dyspnea self-management programs (DSMPs), Internet-based (eDSMP) and face-to-face (fDSMP), compared with a general health education (GHE) control on the primary outcome of dyspnea with activities. Methods. Participants with chronic obstructive pulmonary disease were randomized to eDSMP (n = 43), fDSMP (n = 41), or GHE (n = 41). The content of the DSMPs were similar and focused on education, skills training, and coaching on dyspnea self-management strategies, including exercise, and only differed in the delivery mode. Dyspnea with activities was measured with the Chronic Respiratory Questionnaire at three, six, and 12 months. Secondary outcomes included exercise behavior and performance, health-related quality of life, self-efficacy for dyspnea management, and perception of support for exercise. The study was registered at Clinicaltrials.gov (NCT00461162). Results. There were no differences in dyspnea with activities across groups over 12 months (P = 0.48). With the exception of arm endurance (P = 0.04), exercise behavior, performance, and health-related quality of life did not differ across groups (P > 0.05). Self-efficacy for managing dyspnea improved for the DSMPs compared with GHE (P = 0.06). DSMP participants perceived high levels of support for initiating and maintaining an exercise program. Conclusion. The DSMPs did not significantly reduce dyspnea with activities compared with attention control. However, the high participant satisfaction with the DSMPs combined with positive changes in other outcomes, including self-efficacy for managing dyspnea and exercise behavior, highlight the need for additional testing of individually tailored technology-enabled interventions to optimize patient engagement and improve clinically relevant outcomes. (c) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Nguyen, Huong Q.; Wolpin, Seth; Benditt, Joshua O.] Univ Washington, Seattle, WA 98199 USA. [Reinke, Lynn F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Donesky, DorAnne; Chyall, Lawrence; Paul, Steven M.; Carrieri-Kohlman, Virginia] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Nguyen, HQ (reprint author), Univ Washington, Box 357266, Seattle, WA 98199 USA. EM hqn@u.washington.edu RI Emchi, Karma/Q-1952-2016 FU UCSF [R01 NR008938]; UW GCRCs [MO1-RR-000037, MO1 RR-00079]; National Institutes of Health [1KL2RR025015, 1 UL1 RR025014]; Oncology Nursing Society; Department of Veterans Affairs FX This work was supported in part by UCSF (R01 NR008938), UW GCRCs (MO1-RR-000037 and MO1 RR-00079), and National Institutes of Health grants 1KL2RR025015 and 1 UL1 RR025014. Dr. Reinke has funding through the Oncology Nursing Society and the Department of Veterans Affairs. 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. The authors declare no conflicts of interest. NR 42 TC 26 Z9 27 U1 7 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2013 VL 46 IS 1 BP 43 EP 55 DI 10.1016/j.jpainsymman.2012.06.015 PG 13 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 182MZ UT WOS:000321748500005 PM 23073395 ER PT J AU Shahnazari, M Ceresa, C Foley, S Fong, A Zidaru, E Moody, S AF Shahnazari, Mohammad Ceresa, Carol Foley, Sharon Fong, Angela Zidaru, Elena Moody, Sandra TI Nutrition-Focused Wellness Coaching Promotes a Reduction in Body Weight in Overweight US Veterans SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Veterans; Nutrition coaching; Healthy eating; Weight loss ID CORONARY-HEART-DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIAL; OBESITY; WOMEN; CHOLESTEROL; PREVALENCE; VALIDITY; PROGRAM; RECORDS AB Diet plays a critical role in the pathogenesis of major Chronic diseases common in populations of US veterans. The role of nutrition-focused wellness coaching in improving dietary behavior and/or reducing weight in overweight and obese US veterans is not known. At the San Francisco Veterans Affairs Medical Center, US veterans aged 25 to 80 years were randomized to receive nutrition coaching on eating behaviors at baseline only (control group, n=22) or an additional eight times over the course of 6 months (intervention group, n=28) in 2010-2011. Multiple coaching contacts decreased intake of energy, fat, and carbohydrate by 31% (P <= 0.001) as evaluated by the 2005 Block food frequency questionnaire, which is composed of 111 food items. A weight loss of 5% from baseline (92.8 to 88.2 kg; P<0.01) was observed in the intervention group with mean body mass index decreasing from 30.4 to 28.9 (P<0.05). The control group showed a decrease in fat intake by 20% (P=0.01), but no statistically significant changes in intake of other nutrients or body weight (88.7 to 87.4 kg). Those in the intervention group reported diets at follow-up that were lower in cholesterol, saturated fat, sodium, sugar (P <= 0.01), calcium (P<0.05), and vitamin D (P<0.01), although when adjusted for energy (le, nutrient density) calcium intake increased and vitamin D remained unchanged. Veterans' readiness to change eating behavior for weight loss improved with nutrition coaching. This study demonstrates that intermittent nutrition coaching can be an effective strategy to promote reductions in energy intake, body weight, and body mass index in overweight US veterans. Further research is needed to determine whether nutrition coaching improves other clinical outcomes and sustains weight loss. C1 [Shahnazari, Mohammad] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Ceresa, Carol] San Francisco VA Med Ctr, Nutr & Food Serv, San Francisco, CA 94121 USA. [Foley, Sharon] Rush Univ, Chicago, IL 60612 USA. [Fong, Angela] Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. [Zidaru, Elena] Community Hlth Resource Ctr, San Francisco, CA USA. [Moody, Sandra] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. RP Ceresa, C (reprint author), San Francisco VA Med Ctr, 4150 Clement, San Francisco, CA 94121 USA. EM carol.ceresa@va.gov FU Department of Veterans Affairs, San Francisco VA Medical Center, San Francisco, CA FX The Department of Veterans Affairs, San Francisco VA Medical Center, San Francisco, CA, provided funding for this study. NR 43 TC 6 Z9 6 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD JUL PY 2013 VL 113 IS 7 BP 928 EP 935 DI 10.1016/j.jand.2013.04.001 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183FI UT WOS:000321799300008 PM 23706353 ER PT J AU Salazar, G Quencer, K Aran, S Abujudeh, H AF Salazar, Gloria Quencer, Keith Aran, Shima Abujudeh, Hani TI Patient Satisfaction in Radiology: Qualitative Analysis of Written Complaints Generated Over a 10-Year Period in an Academic Medical Center SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Patient satisfaction; patient complaints; radiology; patient advocacy; root-cause analysis; patient-centered care ID EXPECTATIONS AB Purpose: The aims of this study were to review patients' complaints about their care in radiology and to determine key areas for improvement. Methods: An institutional review board approved, HIPAA-compliant study was conducted to retrospectively evaluate all radiology-related patient complaints received by the authors' institution's Office of Patient Advocacy from April 1999 to December 2010. The internal review classified the complaints into those that concerned medical complications, radiology staff members, failure to provide patient-centered care, and those that related to quality on the basis of radiologic benchmarks of safety, systems, and professionalism. The rate of successful complaint resolution was also tallied. The incidence of complaints per modality was calculated as a fraction of the total number of radiologic examinations performed. Results: A total of 153 radiology-related complaints were identified. The majority of complaints (60.1% [92 of 153]) described a failure to provide patient-centered care. Of the remaining complaints, 26.2% (40 of 153) reported physical discomfort, 10.5% (16 of 153) reported a combination of both physical discomfort and lack of patient-centered care, and 3.2% (5 of 153) were not related to either category. Of the complaints regarding quality, 44.5% (68 of 153) were associated with operational systems, 24.2% (37 of 153) with safety, 17% (26 of 153) with professionalism, and 14.3% (22 of 153) with multifactorial events. Delays accounted for 20.2% of complaints (31 of 153), and 49.6% of complaints (76 of 153) concerned radiology staff members. Complaint resolution was achieved in 83.6% of cases (128 of 153). The overall incidence of complaints per radiologic procedure was 0.238 per 10,000. The incidence of complaints associated with interventional procedures (3.26 per 10,000) was significantly (P < .05) higher than the incidence of those associated with noninterventional examinations (0.138 per 10,000). Conclusions: Failure to provide patient-centered care was the most common complaint; most of these complaints could be attributed to systems issues. There was a higher incidence of complaints related to interventional procedures than diagnostic examinations. Delays and providers' interactions with patients were identified as key areas for improvement. C1 [Salazar, Gloria; Quencer, Keith; Aran, Shima; Abujudeh, Hani] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 213 D,55 Fruit St, Boston, MA 02114 USA. EM habujudeh@parmers.org NR 11 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2013 VL 10 IS 7 BP 513 EP 517 DI 10.1016/j.jacr.2013.03.013 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 185VK UT WOS:000321998200010 PM 23827003 ER PT J AU Wright, CD Akins, CW AF Wright, Cameron D. Akins, Cary W. TI Historical perspectives of The American Association for Thoracic Surgery: Mortimer J. Buckley (1932-2007) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Biographical-Item C1 [Wright, Cameron D.; Akins, Cary W.] Massachusetts Gen Hosp, Dept Thorac Surg, 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 1 TC 1 Z9 1 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 JUL PY 2013 VL 146 IS 1 BP 6 EP 8 DI 10.1016/j.jtcvs.2011.04.035 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 166UH UT WOS:000320583300008 PM 21820674 ER PT J AU Blosnich, J Foynes, MM Shipherd, JC AF Blosnich, John Foynes, Melissa Ming Shipherd, Jillian C. TI Health Disparities Among Sexual Minority Women Veterans SO JOURNAL OF WOMENS HEALTH LA English DT Article ID UNITED-STATES; MENTAL-HEALTH; BISEXUAL ADULTS; FEMALE VETERANS; DONT TELL; GAY; MILITARY; PREVALENCE; SUICIDE; ORIENTATION AB Background: Lesbian and bisexual (i.e., sexual minority) identity is more common among women veterans than among male veterans. Unique health issues have been identified among women veterans and among sexual minority women, but little is known about women who are both sexual minorities and veterans. This study aimed to compare demographic and health information from sexual minority women veterans with sexual minority women non-veterans and heterosexual women veterans. Methods: Behavioral Risk Factor Surveillance Survey data were pooled from ten U. S. states that elected to ask sexual identity during 2010. The analytic sample was comprised of women who identified both their sexual identity and veteran status (n = 1,908). Mental health indicators were frequent mental distress, sleep problems, low social/emotional support, and low satisfaction with life. Health risk indicators included current smoking, overweight, and obesity. Physical health status was defined by three components: disability requiring assistive equipment, > 14 days of poor physical health in the past 30 days, and activity limitations. Results: Compared with heterosexual women veterans, sexual minority women veterans had higher odds of mental distress (odds ratio [OR] = 3.03, 95% confidence interval [CI]: 1.61-5.70) and smoking (OR = 2.31, 95% CI: 1.19-4.48). After adjusting for demographic correlates, sexual minority women veterans had three times the odds of poor physical health (OR = 3.01, 95% CI: 1.51-5.99) than their sexual minority non-veteran peers. Conclusions: Results suggest sexual minority women veterans may experience unique health disparities relevant to provision of care in both Veterans Affairs (VA) and non-VA healthcare systems. Future research requires availability of data that include sexual minority status. C1 [Blosnich, John] VISN2 Ctr Excellence Suicide Prevent, Canandaigua, NY USA. [Blosnich, John] Univ Rochester, Dept Psychiat, Ctr Study & Prevent Suicide, Rochester, NY 14642 USA. [Foynes, Melissa Ming; Shipherd, Jillian C.] Dept Vet Affairs, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Foynes, Melissa Ming; Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Blosnich, J (reprint author), Univ Rochester, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM john.blosnich@va.gov FU Department of Veterans Affairs VISN2 Center of Excellence for Suicide Prevention; National Institute of Mental Health [5T32MH020061] FX The authors thank John Altieri at the VA Health Care Up-state New York (VISN2) Center of Excellence for Suicide Prevention for his assistance in searching for relevant literature on this topic. The authors also thank the individual State BRFSS Coordinators for their assistance in procuring the data. This work was supported by the Department of Veterans Affairs VISN2 Center of Excellence for Suicide Prevention and a post-doctoral fellowship to J.R. Blosnich in an Institutional National Research Service Award from the National Institute of Mental Health (5T32MH020061). NR 47 TC 16 Z9 16 U1 4 U2 25 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 JUL PY 2013 VL 22 IS 7 BP 631 EP 636 DI 10.1089/jwh.2012.4214 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 180UI UT WOS:000321623800008 PM 23746281 ER PT J AU Thakkar, B Aronis, KN Vamvini, MT Shields, K Mantzoros, CS AF Thakkar, Bindiya Aronis, Konstantinos N. Vamvini, Maria T. Shields, Kelsey Mantzoros, Christos S. TI Metformin and Sulfonylureas in Relation to Cancer Risk in Type II Diabetes Patients: A Meta-analysis using primary data of published studies SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review DE Anti-diabetic medications; Diabetes mellitus; Cancer incidence ID GROWTH-FACTOR-I; CHRONIC LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; COLORECTAL-CANCER; PANCREATIC-CANCER; PROSTATE-CANCER; ANTIDIABETIC THERAPY; INCIDENT CANCER; DECREASED RISK AB Introduction. Accumulating evidence suggests that patients with type 2 diabetes mellitus (T2DM) and hyperinsulinemia are at increased risk for developing malignancies. It remains to be fully elucidated whether use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affect cancer incidence in subjects with T2DM. Material & Methods. We performed a meta-analysis using PubMed, of randomized control trials (RCTs), cohorts, and case-control studies published through July 2012 that assess effects of metformin and/or sulfonylurea sulfonylureas on cancer risk at any site, in subjects with T2DM. Fixed and random effects meta-analysis models were used, and the effect size was summarized as relative risk (RR) for RCTs/cohorts and as odds ratio (OR) for the case-control studies. Results. Analysis of 24 metformin studies in subjects with T2DM showed that metformin use is associated with reduced risk for the development of cancer, in both cohort (RR=0.70 [95% CI=0.67-0.731) and case-control studies (OR=0.90 [95% CI=0.84-0.98]), but this finding was not supported by RCTs (RR=1.01[95% CI=0.81-1.26]). Data from 18 sulfonylurea studies in subjects with T2DM showed that sulfonylurea use is associated with an increase in all-cancer risk, in cohort studies (RR=1.55 [95% CI=1.48-1.63]), though data from RCTs (RR=1.17 [95% CI=0.95-1.45]) and case-control studies (OR=1.02 [95% CI=0.93-1.13]) failed to demonstrate a statistically significant effect. Conclusions. This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM. These findings need to be confirmed in large-scale RCTs before they are translated into clinical practice. Published by Elsevier Inc. C1 [Thakkar, Bindiya; Aronis, Konstantinos N.; Shields, Kelsey; Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. [Thakkar, Bindiya] Boston Univ, Sch Med, Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Thakkar, Bindiya; Aronis, Konstantinos N.; Vamvini, Maria T.; Shields, Kelsey; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. [Aronis, Konstantinos N.] Boston Univ, Sch Med, Dept Internal Med, Boston Med Ctr, Boston, MA 02118 USA. RP Thakkar, B (reprint author), Div Endocrinol Diabet & Metab, 150 S Huntington Ave 9B-52A, Boston, MA 02130 USA. EM Bindiya.Thakkar@bmc.org RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK058785, DK079929, DK081913]; National Institute on Aging [AG032030]; Clinical Science Research and Development Service of VA Office of Research and Development [1I01CX000422-01A1] FX The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants DK058785, DK079929 and DK081913), and the National Institute on Aging (grant AG032030); as well as Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 65 TC 58 Z9 61 U1 1 U2 32 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2013 VL 62 IS 7 BP 922 EP 934 DI 10.1016/j.metabol.2013.01.014 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175IT UT WOS:000321225100004 PM 23419783 ER PT J AU Ducani, C Kaul, C Moche, M Shih, WM Hogberg, B AF Ducani, Cosimo Kaul, Corinna Moche, Martin Shih, William M. Hogberg, Bjorn TI Enzymatic production of 'monoclonal stoichiometric' single-stranded DNA oligonucleotides SO NATURE METHODS LA English DT Article ID FOLDING DNA; NANOSCALE SHAPES; GENE SYNTHESIS; ORIGAMI; DELIVERY; NANOPARTICLES; MICROCHIPS; FIDELITY AB Single-stranded oligonucleotides are important as research tools, as diagnostic probes, in gene therapy and in DNA nanotechnology. Oligonucleotides are typically produced via solid-phase synthesis, using polymer chemistries that are limited relative to what biological systems produce. The number of errors in synthetic DNA increases with oligonucleotide length, and the resulting diversity of sequences can be a problem. Here we present the 'monoclonal stoichiometric' (MOSIC) method for enzyme-mediated production of DNA oligonucleotides. We amplified oligonucleotides from clonal templates derived from single bacterial colonies and then digested cutter hairpins in the products, which released pools of oligonucleotides with precisely controlled relative stoichiometric ratios. We prepared 14-378-nucleotide MOSIC oligonucleotides either by in vitro rolling-circle amplification or by amplification of phagemid DNA in Escherichia coli. Analyses of the formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides. C1 [Ducani, Cosimo; Kaul, Corinna; Hogberg, Bjorn] Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, Stockholm, Sweden. [Moche, Martin] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden. [Shih, William M.] Wyss Inst Biol Inspired Engn Harvard, Boston, MA USA. [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Hogberg, B (reprint author), Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, Stockholm, Sweden. EM bjorn.hogberg@ki.se RI Kaul, Corinna/H-5132-2013; OI Hogberg, Bjorn/0000-0003-2715-7887; Moche, Martin/0000-0002-4834-7076 FU Swedish Research Council (Vetenskapsradet) [2010-6296, 2010-5060]; Carl Bennet AB; Karolinska Institutet; Vinnova FX Funded by the Swedish Research Council (Vetenskapsradet) through a repatriation grant and a project grant to B. H. (grants 2010-6296 and 2010-5060). B. H. is a recipient of an assistant professorship with startup funding by Carl Bennet AB, Karolinska Institutet and Vinnova. We thank S. Douglas for help with the 10-helix bundle design, members of the Laboratory of Chemical Biology at Karolinska Institutet for HPLC support, T. Karlberg and members of the Protein Science Facility for crystallography support, M. Schultz and C. Sanden for help with pseudogene cloning and enzymatic reactions for the long ODNs, and N. Seeman for fruitful discussions. NR 31 TC 24 Z9 24 U1 2 U2 71 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JUL PY 2013 VL 10 IS 7 BP 647 EP + DI 10.1038/NMETH.2503 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 172LV UT WOS:000321006000027 PM 23727986 ER PT J AU Longo, FM Massa, SM AF Longo, Frank M. Massa, Stephen M. TI Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID NERVE GROWTH-FACTOR; TRKB AGONIST 7,8-DIHYDROXYFLAVONE; MILD COGNITIVE IMPAIRMENT; BETA-TURN PEPTIDOMIMETICS; RETINAL GANGLION-CELLS; AFFINITY NGF RECEPTOR; SPINAL-CORD-INJURY; ALZHEIMERS-DISEASE; MOUSE MODEL; INTRACELLULAR DOMAIN AB Neurotrophins and their receptors modulate multiple signalling pathways to regulate neuronal survival and to maintain axonal and dendritic networks and synaptic plasticity. Neurotrophins have potential for the treatment of neurological diseases. However, their therapeutic application has been limited owing to their poor plasma stability, restricted nervous system penetration and, importantly, the pleiotropic actions that derive from their concomitant binding to multiple receptors. One strategy to overcome these limitations is to target individual neurotrophin receptors-such as tropomyosin receptor kinase A (TRKA), TRKB, TRKC, the p75 neurotrophin receptor or sortilin-with small-molecule ligands. Such small molecules might also modulate various aspects of these signalling pathways in ways that are distinct from the programmes triggered by native neurotrophins. By departing from conventional neurotrophin signalling, these ligands might provide novel therapeutic options for a broad range of neurological indications. C1 [Longo, Frank M.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Massa, Stephen M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Neurol, San Francisco, CA 94121 USA. RP Longo, FM (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, 300 Pasteur Dr, Stanford, CA 94305 USA. EM longo@stanford.edu; stephen.massa@ucsf.edu FU NIA [UO1 AG032225]; Alzheimer's Drug Discovery Foundation; Alzheimer's Association; Eastern Chapter of the North Carolina Alzheimer's Association; Koret Foundation; Taube Philanthropies; Jean Perkins Foundation; Horngren Family Alzheimer's Research Fund; Richard M. Lucas Foundation; US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX Work by the authors has been supported by grants from the following bodies: NIA UO1 AG032225 (to F.M.L.); the Alzheimer's Drug Discovery Foundation (to F.M.L.); the Alzheimer's Association (to F.M.L.); the Eastern Chapter of the North Carolina Alzheimer's Association (to F.M.L.); the Koret Foundation (to F.M.L.); the Taube Philanthropies (to F.M.L.); the Jean Perkins Foundation (to F.M.L.); the Horngren Family Alzheimer's Research Fund (to F.M.L.); the Richard M. Lucas Foundation (to F.M.L.); and the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (to S.M.M). NR 217 TC 71 Z9 75 U1 7 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JUL PY 2013 VL 12 IS 7 BP 507 EP 525 DI 10.1038/nrd4024 PG 19 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 173VU UT WOS:000321110600016 PM 23977697 ER PT J AU Sun, CC Vaja, V Chen, SZ Theurl, I Stepanek, A Brown, DE Cappellini, MD Weiss, G Hong, CC Lin, HY Babitt, JL AF Sun, Chia Chi Vaja, Valentina Chen, Shanzhuo Theurl, Igor Stepanek, Aaron Brown, Diane E. Cappellini, Maria D. Weiss, Guenter Hong, Charles C. Lin, Herbert Y. Babitt, Jodie L. TI A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE anemia; chronic kidney disease; hepcidin; iron; mouse model ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CHRONIC-RENAL-FAILURE; HEMODIALYSIS-PATIENTS; INTRAVENOUS IRON; GLOMERULAR INJURY; DEFICIENCY ANEMIA; ELEVATED FERRITIN; EPOETIN-ALPHA; IN-VIVO; EXPRESSION AB Background. Anemia is a common complication of chronic kidney disease (CKD) that negatively impacts the quality of life and is associated with numerous adverse outcomes. Excess levels of the iron regulatory hormone hepcidin are thought to contribute to anemia in CKD patients by decreasing iron availability from the diet and from body stores. Adenine treatment in rats has been proposed as an animal model of anemia of CKD with high hepcidin levels that mirrors the condition in human patients. Methods. We developed a modified adenine-induced kidney disease model with a higher survival rate than previously reported models, while maintaining persistent kidney disease and anemia. We then tested whether the small molecule bone morphogenetic protein (BMP) inhibitor LDN-193189, which was previously shown to lower hepcidin levels in rodents, mobilized iron into the plasma and improved iron-restricted erythropoiesis in this model. Results. Adenine-treated rats exhibited increased hepatic hepcidin mRNA, decreased serum iron, increased spleen iron content, low hemoglobin (Hb) and inappropriately low erythropoietin (EPO) levels relative to the degree of anemia. LDN-193189 administration to adenine-treated rats lowered hepatic hepcidin mRNA, mobilized stored iron into plasma and increased Hb content of reticulocytes. Conclusions. Our data suggest that hepcidin lowering agents may provide a new therapeutic strategy to improve iron availability for erythropoiesis in CKD. C1 [Sun, Chia Chi; Vaja, Valentina; Chen, Shanzhuo; Theurl, Igor; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Membrane Biol,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol, Boston, MA 02115 USA. [Vaja, Valentina; Cappellini, Maria D.] Univ Milan, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Milan, Italy. [Theurl, Igor; Weiss, Guenter] Med Univ Innsbruck, Dept Internal Med Clin Immunol & Infect Dis 1, A-6020 Innsbruck, Austria. [Stepanek, Aaron; Brown, Diane E.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Brown, Diane E.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hong, Charles C.] Vet Affairs TVHS, Vanderbilt Sch Med, Nashville, TN USA. RP Babitt, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Membrane Biol,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol, Boston, MA 02115 USA. EM babitt.jodie@mgh.harvard.edu OI Weiss, Guenter/0000-0003-0709-2158; CAPPELLINI, MARIA DOMENICA/0000-0001-8676-6864 FU NIH NRSA [T32 DK 7540-27]; NIH [RO1-DK087727, RO1 DK-069533, RO1 DK-071837]; National Kidney Foundation; Massachusetts General Hospital FX C.C.S was supported by NIH NRSA Training grant T32 DK 7540-27. J.L.B was supported in part by NIH grant RO1-DK087727, the Satellite Dialysis Young Investigator Grant of the National Kidney Foundation, and Claflin Distinguished Scholar and Howard Goodman Fellowship Awards from the Massachusetts General Hospital. H.Y.L was supported by NIH grants RO1 DK-069533 and RO1 DK-071837. NR 59 TC 23 Z9 23 U1 3 U2 9 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 JUL PY 2013 VL 28 IS 7 BP 1733 EP 1743 DI 10.1093/ndt/gfs584 PG 11 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 183ND UT WOS:000321821900017 PM 23345622 ER PT J AU Ginat, DT Freitag, SK Kieff, D Grove, A Fay, A Cunnane, M Moonis, G AF Ginat, Daniel T. Freitag, Suzanne K. Kieff, David Grove, Arthur Fay, Aaron Cunnane, Marybeth Moonis, Gul TI Radiographic Patterns of Orbital Involvement in IgG4-Related Disease SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SYSTEMIC-DISEASE; SCLEROSING DISEASE; NECK; HEAD; INFLAMMATION; BRAIN AB Purpose: Immunoglobin G4 (IgG4)-related disease is a systemic condition characterized by lymphoplasmacytic infiltrates that can involve the orbit. The purpose of this study was to identify the various patterns of orbital IgG4-related disease on imaging. Methods: Retrospective review of radiologic examinations including CT, MRI, and positron emission tomography was performed in patients with proven cases of IgG4-related disease. Results: A total of 9 patients with orbital IgG4-related disease were identified, including 9 with CT, 4 with MRI, and 4 with 18-fluorodeoxyglucose positron emission tomography. Patterns of involvement included lacrimal gland enlargement, lacrimal sac involvement, extraocular muscle thickening, preseptal involvement, orbital fat involvement, and cranial nerve involvement, many of which occurred simultaneously. Associated demineralization of the orbital wall was evident on CT in 2 cases. On T2-weighted MRI, the lesions appeared as hypointense in 2 cases, heterogeneously hypointense to isointense in 1 case, and hyperintense in 1 case. Diffuse enhancement was present in all 3 cases in which postcontrast T1-weighted sequences were available. The lesions were hypermetabolic on positron emission tomography in 3 of 4 cases. There was definite extraorbital involvement by IgG4-related disease in 3 of the 9 patients and suspected involvement in another 3 of the 9 patients. Conclusions: IgG4-related disease displays a wide variety of imaging manifestations in the orbit. Extraorbital disease is often present and can help suggest the diagnosis. C1 [Ginat, Daniel T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Freitag, Suzanne K.; Grove, Arthur; Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Kieff, David] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Cunnane, Marybeth] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Moonis, Gul] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Beth Israel Deaconess Med Ctr,Dept Radiol, Boston, MA 02115 USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 18 TC 13 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2013 VL 29 IS 4 BP 261 EP 266 DI 10.1097/IOP.0b013e31829165ad PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 181VS UT WOS:000321698400013 PM 23645355 ER PT J AU Fay, A Nallassamy, N Pemberton, JD Callahan, A Wladis, EJ Nguyen, J Durand, ML AF Fay, Aaron Nallassamy, Nambi Pemberton, John D. Callahan, Allison Wladis, Edward J. John Nguyen Durand, Marlene L. CA New England Oculoplast Soc Study TI Prophylactic Postoperative Antibiotics for Enucleation and Evisceration SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CARE IMPROVEMENT PROJECT; ANTIMICROBIAL PROPHYLAXIS; RECONSTRUCTIVE SURGERY; INFECTIONS; ENDOPHTHALMITIS; IMPLANTS; ALLERGY AB Purpose: To investigate the necessity and usefulness of prophylactic postoperative antibiotics in patients undergoing enucleation or ocular evisceration. Methods: A retrospective, multicenter, comparative case series was designed. After obtaining Institutional Review Board authorization, a medical records' review was conducted. Demographics, indication for surgery, surgical technique, postoperative antibiotic dosing, and postoperative course were evaluated. Records were grouped according to antibiotic protocols, and presence or absence of postoperative wound infection (orbital cellulitis) was recorded. Rates of postoperative infection were analyzed statistically. Results: Between 1996 and 2011, 666 evisceration or enucleation surgeries were conducted at 4 institutions. Six hundred forty-eight records were available for analysis, of which 4 were excluded due to insufficient follow-up data. All the remaining 644 patients received a single, perioperative, intravenous dose of antibiotics. Five hundred seventy-eight patients (90%) received an orbital implant, while 66 (10%) did not. Three hundred eighty-one patients (59%) received postoperative antibiotics, and 263 patients (41%) did not. Two cases were identified with signs suggestive of infection, but no culture-positive infections were found, and no patient was admitted to the hospital for management. Of the 2 suspicious cases, 1 was found in the group that received postoperative antibiotics (group 1) and 1 in the group that did not receive postoperative antibiotics (group 2). No statistically significant difference in postoperative infection rate was noted between the 2 groups (p = 0.52). While patients with infectious indications for surgery were more likely to receive postoperative antibiotics (p < 0.001), there was no statistically significant difference in rates of infection among patients with infectious indications for surgery based on receiving or not receiving postoperative antibiotics (p = 0.79), and no patients with infectious indications for surgery not receiving postoperative antibiotics developed a postoperative infection. Conclusions: This study demonstrates the clinical safety of withholding postoperative prophylactic antibiotics in orbital surgery even when implanting alloplastic material in a sterile field. Furthermore, Centers for Disease Control and Prevention guidelines mandate cessation of postoperative antibiotics within 24 hours of surgery. Surgeons are cautioned not to generalize these results to nonsterile surgery such as sinonasal or nasolacrimal surgery. C1 [Fay, Aaron; Callahan, Allison] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Fay, Aaron; Nallassamy, Nambi] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Pemberton, John D.] Univ Arkansas Med Sci, Dept Ophthalmol, Little Rock, AR 72205 USA. [Pemberton, John D.] Jones Eye Inst, Little Rock, AR USA. [Wladis, Edward J.] Albany Med Coll, Lions Eye Inst, Dept Ophthalmol, Albany, NY 12208 USA. [John Nguyen] W Virginia Univ, Sch Med, Dept Ophthalmol, Morgantown, WV 26506 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu OI Pemberton, John/0000-0001-6305-4653 NR 31 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2013 VL 29 IS 4 BP 281 EP 285 DI 10.1097/IOP.0b013e3182916674 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 181VS UT WOS:000321698400017 PM 23645357 ER PT J AU Mendoza, PR Jakobiec, FA Townsend, DJ AF Mendoza, Pia R. Jakobiec, Frederick A. Townsend, Daniel J. TI Bilateral Nevus Comedonicus of the Eyelids SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID FAVRE-RACOUCHOT-DISEASE; EPIDERMAL NEVUS; INVOLVEMENT; FEATURES; BODY AB Nevus comedonicus is a rare developmental abnormality of the infundibulum of the hair follicle. It is usually unilateral and commonly presents at birth or during childhood. A rare case of late-onset, bilateral nevus comedonicus of the eyelids is reported. A 79-year-old man presented with asymptomatic but disfiguring eyelid lesions noted several months earlier. On physical examination, multiple papules resembling comedones were present bilaterally in the eyelids, canthi, temple regions, and bridge of the nose. Microscopically, there were deep invaginations of the follicular canals forming focal tunnels or pseudosinus tracts with poral openings to the surface. These variably cystic structures were lined by keratinizing and nonkeratinizing squamous epithelium, contained concentric lamellae of keratin in their lumens, and some were acutely or chronically inflamed. The diagnosis of a nevus comedonicus was made. The clinical and histopathologic characteristics, pathogenesis, differential diagnosis, and management of nevus comedonicus are briefly discussed. C1 [Mendoza, Pia R.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Mendoza, Pia R.; Jakobiec, Frederick A.; Townsend, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Mendoza, Pia R.; Jakobiec, Frederick A.; Townsend, Daniel J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, 3rd Floor,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 27 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2013 VL 29 IS 4 BP E95 EP E98 DI 10.1097/IOP.0b013e31827bdadb PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 181VS UT WOS:000321698400002 PM 23328782 ER PT J AU Patel, MM Lefebvre, DR Lee, NG Brachtel, E Rizzo, J Freitag, SK AF Patel, Mrinali M. Lefebvre, Daniel R. Lee, N. Grace Brachtel, Elena Rizzo, Joseph Freitag, Suzanne K. TI Gaze-Evoked Amaurosis From Orbital Breast Carcinoma Metastasis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID FUGAX AB Gaze-evoked amaurosis (GEA) is a transient monocular vision loss provoked by eccentric gaze. Gaze-evoked amaurosis has been associated with a variety of orbital lesions, most commonly optic nerve sheath meningiomas and cavernous hemangiomas. The authors describe the first report in the literature of GEA as the presenting symptom of an orbital metastasis. The patient was a 47-year-old woman with a history of breast cancer with no known history of metastasis or active disease who presented with several weeks of vision loss in the OD upon rightward gaze. She was found to have enophthalmos and optic disc edema of the OD. Imaging revealed an intraorbital lesion, and a biopsy was consistent with a scirrhous metastasis of her breast carcinoma. This case highlights the importance of considering orbital metastases among the differential for gaze-evoked amaurosis. C1 [Patel, Mrinali M.; Lefebvre, Daniel R.; Lee, N. Grace; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Surg Serv,Dept Ophthalmol, Boston, MA USA. [Patel, Mrinali M.; Rizzo, Joseph] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Neuroophthalmol Serv,Dept Ophthalmol, Boston, MA USA. [Brachtel, Elena] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Freitag, SK (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Plast Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM Suzanne_Freitag@meei.harvard.edu NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2013 VL 29 IS 4 BP E98 EP E101 DI 10.1097/IOP.0b013e31827defc7 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 181VS UT WOS:000321698400003 PM 23446302 ER PT J AU Stacy, RC Jakobiec, FA Fay, A AF Stacy, Rebecca C. Jakobiec, Frederick A. Fay, Aaron TI Collagenous Fibroma (Desmoplastic Fibroblastoma) of the Orbital Rim SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CONJUNCTIVAL FIBROMA AB A 40-year-old woman with left periorbital swelling for 1 month presented without diplopia or change in vision. Imaging studies revealed a 1-cm mass at the frontozygomatic junction at the orbital rim with slight bony erosion and spiculation. The lesion was applied to the periosteum and was excised along with a portion of the bony orbital rim. Histopathology revealed elongated and stellate fibroblasts within a dense collagenous matrix. Vimentin and Masson trichrome staining was consistent with a collagenous fibroma, a rare tumor that has, only once before, been reported in the orbit in the lacrimal fossa region. The current collagenous fibroma arose from the periosteum to grow exophytically, causing minimal bone changes. A literature review shows that this condition predominantly affects middle-aged and older adults rather than children. C1 [Stacy, Rebecca C.; Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA USA. [Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Oculoplast Div, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, DG Cogan Pathol Lab, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JUL-AUG PY 2013 VL 29 IS 4 BP E101 EP E104 DI 10.1097/IOP.0b013e31827deffe PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 181VS UT WOS:000321698400004 PM 23446303 ER PT J AU Balon, R Alpert, JE Cluver, JS Lewis, C AF Balon, Richard Alpert, Jonathan E. Cluver, Jeffrey S. Lewis, Catherine CA ADMSEP Task Force Res Scholarship TI How to Get Help With Starting Your Research Project: ADMSEP Task Force on Research and Scholarship SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 [Balon, Richard] Wayne State Univ, Detroit, MI USA. [Alpert, Jonathan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cluver, Jeffrey S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Lewis, Catherine] Univ Connecticut, Farmington, CT USA. RP Balon, R (reprint author), UPC Jefferson, Detroit, MI USA. EM rbalon@wayne.edu OI Alpert, Jonathan/0000-0002-4332-908X NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2013 VL 37 IS 4 BP 221 EP 222 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 178YT UT WOS:000321484000001 PM 23820904 ER PT J AU Landsberger, SA Scott, EL Hulvershorn, LA Chapleau, KM Diaz, DR McDougle, CJ AF Landsberger, Sarah Anne Scott, Eric L. Hulvershorn, Leslie A. Chapleau, Kristine M. Diaz, David R. McDougle, Christopher J. TI Mentorship of Clinical-Track Junior Faculty: Impact of a Facilitated Peer-Mentming Program to Promote Scholarly Productivity SO ACADEMIC PSYCHIATRY LA English DT Letter C1 [Landsberger, Sarah Anne] Indiana Univ, Sch Med, Dept Psychiat, Psychol Sect, Indianapolis, IN 46202 USA. [Scott, Eric L.; Hulvershorn, Leslie A.; Chapleau, Kristine M.; Diaz, David R.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Landsberger, SA (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Psychol Sect, Indianapolis, IN 46202 USA. EM slandsbe@iupui.edu RI Hulvershorn, Leslie/J-3421-2013 OI Hulvershorn, Leslie/0000-0001-5827-4889 NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUL-AUG PY 2013 VL 37 IS 4 BP 288 EP 289 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 178YT UT WOS:000321484000019 PM 23820920 ER PT J AU Chen, WP Liu, YH Ho, YJ Wu, SM AF Chen, Wen-pin Liu, Yuan-hung Ho, Yi-jin Wu, Sean M. TI A83-01, a TGF beta RI inhibitor, can proliferate adult cardiac progenitor cells and improve cardiac contractility of myocardial infarcted mice SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract DE Nkx2.5; TGF beta; ALK5; A83-01 C1 [Chen, Wen-pin; Ho, Yi-jin] Natl Taiwan Univ, Coll Med, Inst Pharmacol, Taipei, Taiwan. [Liu, Yuan-hung] Far Eastern Mem Hosp, Dept Cardiovasc Med, Taipei, Taiwan. [Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2013 VL 34 SU S BP 57 EP 57 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 186NO UT WOS:000322051500249 ER PT J AU Sheng, R Qin, T Qin, ZH Smith, CD Sapp, E Difiglia, M Waeber, C AF Sheng, Rui Qin, Tao Qin, Zheng-hong Smith, Charles D. Sapp, Ellen Difiglia, Marian Waeber, Christian TI Sphingosine kinase 2-mediated autophagy contributes to preconditioning by isoflurane in mouse cortical neurons SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract DE sphingosine kinase 2; isoflurane preconditioning; autophagy; cortical neurons; coimmunoprecipitation C1 [Sheng, Rui; Qin, Tao; Waeber, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA. [Sheng, Rui; Qin, Zheng-hong] Soochow Univ, Sch Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Peoples R China. [Sheng, Rui; Qin, Zheng-hong] Soochow Univ, Lab Aging & Nervous Dis, Sch Pharmaceut Sci, Suzhou 215123, Peoples R China. [Smith, Charles D.] Apogee Biotechnol Corp, Hummelstown, PA 17036 USA. [Sapp, Ellen; Difiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Sapp, Ellen; Difiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2013 VL 34 SU S BP 112 EP 112 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 186NO UT WOS:000322051500494 ER PT J AU Hage, FG Lusa, L Dondi, M Giubbini, R Iskandrian, AE AF Hage, Fadi G. Lusa, Lara Dondi, Maurizio Giubbini, Raffaele Iskandrian, Ami E. CA IAEA Diabet Investigators TI Exercise Stress Tests for Detecting Myocardial Ischemia in Asymptomatic Patients With Diabetes Mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; PERFUSION; DIAD; RISK; OUTCOMES; ELECTROCARDIOGRAPHY; GUIDELINES; TRIAL AB The predominant cause of death in diabetes mellitus (DM) is coronary artery disease (CAD). Little is known about prevalence of silent ischemia in developing nations. We compared prevalence of silent ischemia in DM to a control group by exercise myocardial perfusion imaging (MPI) and electrocardiogram (ECG) in developing nations. The prospective multinational Ischemia Assessment with Exercise imaging in Asymptomatic Diabetes study recruited. participants at 12 sites in Asia, Africa, and Latin America. DM participants were age- and gender-matched 2:1 to non-DM individuals with >= 1 CAD risk factor. Subjects, underwent exercise tests that were interpreted in core labs in blinded fashion. The study included 392 DM and 205 control participants. Among participants with diagnostic ECGs, a similar proportion of DM and controls had ischemic ECG (15% vs 12%, p = 0.5). A significantly higher proportion of DM group had MPI abnormalities compared with controls (26% vs 14%, p <0.001). In participants with ischemia on MPI, only 17% had ischemic ECG, whereas in those without ischemia on MPI, 10% had ischemic ECG. In a multivariable model, DM was independently associated with abnormal MPI (odds ratio 2.1, 95% confidence interval 1.3-3.5, p = 0.004). Women were less likely to have ischemia by MPI than men (10% vs 30%, p <0.001) and concordance between ECG and MPI was much worse in women. In conclusion, in this large prospective study, asymptomatic DM participants had (1) more ischemia by exercise MPI than ECG, (2) more ischemia by MPI but not ECG than control group, and (3) ischemia by MPI was less in women than men. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hage, Fadi G.; Iskandrian, Ami E.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Lusa, Lara] Univ Ljubljana, Inst Biostat & Med Informat, Fac Med, Ljubljana 61000, Slovenia. [Dondi, Maurizio] IAEA, Nucl Med Sect, Div Human Hlth, A-1400 Vienna, Austria. [Giubbini, Raffaele] Univ Brescia, I-25121 Brescia, Italy. RP Hage, FG (reprint author), Univ Alabama Birmingham, Birmingham, AL 35294 USA. EM fadihage@uab.edu RI Lusa, Lara/C-6692-2015; OI Lusa, Lara/0000-0002-8981-2421; Hage, Fadi/0000-0002-1397-4942 FU International Atomic Energy Agency [E1.30.31] FX This study was supported by the International Atomic Energy Agency through the Coordinated Research Project E1.30.31. NR 24 TC 5 Z9 8 U1 0 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 2013 VL 112 IS 1 BP 14 EP 20 DI 10.1016/j.amjcard.2013.02.047 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 181OA UT WOS:000321677200003 PM 23578350 ER PT J AU Rao, AD Shah, RV Garg, R Abbasi, SA Neilan, TG Perlstein, TS Di Carli, MF Jerosch-Herold, M Kwong, RY Adler, GK AF Rao, Ajay D. Shah, Ravi V. Garg, Rajesh Abbasi, Siddique A. Neilan, Tomas G. Perlstein, Todd S. Di Carli, Marcelo F. Jerosch-Herold, Michael Kwong, Raymond Y. Adler, Gail K. TI Aldosterone and Myocardial Extracellular Matrix Expansion in Type 2 Diabetes Mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; DIASTOLIC DYSFUNCTION; DIETARY-SODIUM; BLOOD-FLOW; FIBROSIS; EPLERENONE; ASSOCIATION; SPIRONOLACTONE; QUANTIFICATION; CARDIOMYOPATHY AB Myocardial extracellular matrix expansion and reduced coronary flow reserve (CFR) occur in patients with type 2 diabetes mellitus without heart failure or coronary artery disease. Because aldosterone is implicated in the pathophysiology of cardiac fibrosis and vascular injury, the aim of this study was to test the hypothesis that aldosterone is associated with extracellular matrix expansion and reduced CFR in type 2 diabetes mellitus. Patients with type 2 diabetes mellitus without evidence of coronary artery disease were recruited. Blood pressure, lipid management, and glycemic control were optimized over 3 months. Cardiac magnetic resonance imaging with T1 mapping was used to measure myocardial extracellular volume (ECV). Cardiac positron emission tomography was used to assess CFR. On a liberal, 250 mEq/day sodium diet, 24-hour urinary aldosterone and change in serum aldosterone with angiotensin II stimulation were measured. Fifty-three participants with type 2 diabetes (68% men, mean age 53 +/- 7 years, mean body mass index 32.2 +/- 4.3 kg/m(2), mean glycosylated hemoglobin 6.8 +/- 0.7%, mean systolic blood pressure 126 +/- 14 mm Hg) without infarction or ischemia by cardiac magnetic resonance and positron emission tomography were studied. Subjects had impaired CFR (2.51 +/- 0.83) and elevated ECV (0.36 +/- 0.05), despite normal echocardiographic diastolic function and normal left ventricular function. Myocardial ECV, but not CFR, was positively associated with 24-hour urinary aldosterone excretion (r = 0.37, p = 0.01) and angiotensin II stimulated aldosterone increase (r = 0.35, p = 0.02). In a best-overall multivariate model (including age, gender, body mass index, glycosylated hemoglobin, and blood pressure), 24-hour urinary aldosterone was the strongest predictor of myocardial ECV (p = 0.004). In conclusion, in patients with type 2 diabetes mellitus without coronary artery disease, aldosterone is associated with myocardial extracellular matrix expansion. These results implicate aldosterone in early myocardial remodeling in type 2 diabetes mellitus. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rao, Ajay D.; Garg, Rajesh; Adler, Gail K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA 02115 USA. [Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G.; Di Carli, Marcelo F.; Kwong, Raymond Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Noninvas Cardiovasc Imaging Sect, Boston, MA 02115 USA. [Perlstein, Todd S.; Di Carli, Marcelo F.; Kwong, Raymond Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shah, Ravi V.; Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Adler, GK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA 02115 USA. EM gadler@partners.org RI Rao, Ajay/I-2997-2013; OI Rao, Ajay/0000-0002-2550-6097; Abbasi, Siddique/0000-0002-9601-7565 FU National Institutes of Health, Bethesda, Maryland [R01 HL 087060, K24 HL 103845, UL1 TR 000170, R01 HL 090634] FX This project was supported by Grants R01 HL 087060, K24 HL 103845, UL1 TR 000170, and R01 HL 090634 from the National Institutes of Health, Bethesda, Maryland. NR 30 TC 9 Z9 9 U1 0 U2 9 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 2013 VL 112 IS 1 BP 73 EP 78 DI 10.1016/j.amjcard.2013.02.060 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 181OA UT WOS:000321677200013 PM 23597770 ER PT J AU Kalapatapu, RK Delucchi, KL AF Kalapatapu, Raj K. Delucchi, Kevin L. TI APOE e4 genotype and cigarette smoking in adults with normal cognition and mild cognitive impairment: a retrospective baseline analysis of a national dataset SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE APOE; e4; cognitive; cigarette smoking; mild cognitive impairment; neurocognitive ID UNIFORM DATA SET; EPSILON 4 ALLELE; APOLIPOPROTEIN-E; ALZHEIMER-DISEASE; TEST-BATTERY; CESSATION; RISK; UDS; PHARMACOGENETICS; METAANALYSIS AB Background: APOE e4 genotype is known to be a risk factor for Alzheimer's disease and atherosclerosis. Recently, published evidence has shown that APOE e4 genotype may also be associated with the cessation of cigarette smoking. Objectives: The aim of this retrospective analysis was to explore whether any past smoking outcomes differed based on APOE e4 genotype in a large national dataset. Methods: Data were extracted from the National Alzheimer's Coordinating Center's longitudinal Uniform Data Set study. We limited this retrospective baseline analysis to the normal cognition (n = 2995) and mild cognitive impairment (n = 1627) groups that had APOE genotype and smoking data. Because this was an exploratory retrospective analysis, we conducted descriptive analyses on all variables based on APOE e4 genotype. We controlled for demographic, clinical, medication and neurocognitive data in the analyses. Results: In both the normal cognition group and the mild cognitive impairment group, e4 carriers and e4 non-carriers did not significantly differ on total years smoked, age when last smoked and the average # of packs/day smoked during the years they smoked. In both groups, e4 carriers and e4 non-carriers differed on various neurocognitive measures. Conclusion: These data do not support the recently published evidence of the association between APOE e4 genotype and smoking outcomes. Scientific Significance: Larger prospective clinical trials are needed to further explore the relationship between APOE genotype and smoking outcomes. C1 [Kalapatapu, Raj K.; Delucchi, Kevin L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Kalapatapu, Raj K.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Opioid Replacement Treatment Clin, Bldg 1,Ground Floor,Mailstop 116F,4150 Clement St, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com FU NIA NIH HHS [U01 AG016976, K01 AG027295, UO1 AG016976]; NIDA NIH HHS [K23 DA034883, K23DA034883, P50 DA009253, P50DA009253, T32 DA007294] NR 42 TC 2 Z9 3 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JUL PY 2013 VL 39 IS 4 BP 219 EP 226 DI 10.3109/00952990.2013.800084 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 180JT UT WOS:000321590700001 PM 23808899 ER PT J AU Rogg, JG Rubin, JT Hansen, P Liu, SW AF Rogg, Jonathan G. Rubin, J. Tyler Hansen, Paul Liu, Shan W. TI The frequency and cost of redundant laboratory testing for transferred ED patients SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article AB Introduction: Health care costs continue to rise; reducing unnecessary laboratory testing may reduce costs. The goal of this study was to calculate the frequency and estimated costs of repeat normal laboratory testing of patients transferred to a tertiary care emergency department (ED). Methods: This was a retrospective cohort study of patients transferred to a tertiary care, level -one trauma ED with an annual census of 90,000 patients. We defined "repeat normal testing" as laboratory tests repeated within 8 hours that were normal at both the sending hospital and the receiving tertiary care hospital. We estimated the charges associated with repeat normal laboratory testing for 11 common ED tests: basic metabolic panel, calcium, magnesium, phosphorus, lipase, thyroids stimulating hormone, prothrombin time, partial thromboplastin time, complete blood count, liver function test, and urine analysis. Results: Two hundred thirty-two patients were transferred to the receiving tertiary care hospital from within the hospital's network from May 1, 2011, to October 31, 2011. On average, each transferred patient had one repeat normal laboratory test (245/232 = 1.06). For all laboratory tests, repeat normal testing occurred at least 40% of the time. Extrapolating the data, the total yearly estimated charges of all repeat normal testing was $580,526. Conclusion: This study provides the first analysis of the frequency of repeated laboratory testing for all transferred ED patients and indicates that repeat normal testing represents a significant cost. Future research needs to determine if such repeat testing is indeed clinically appropriate or redundant. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rogg, Jonathan G.] Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Rubin, J. Tyler; Hansen, Paul; Liu, Shan W.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Liu, Shan W.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. RP Rogg, JG (reprint author), Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. FU MACEP FX MACEP resident research grant. NR 8 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2013 VL 31 IS 7 BP 1121 EP 1123 DI 10.1016/j.ajem.2013.03.037 PG 3 WC Emergency Medicine SC Emergency Medicine GA 179VR UT WOS:000321550400023 PM 23702071 ER PT J AU Nishihara, R Morikawa, T Kuchiba, A Lochhead, P Yamauchi, M Liao, XY Imamura, Y Nosho, K Shima, K Kawachi, I Qian, ZR Fuchs, CS Chan, AT Giovannucci, E Ogino, S AF Nishihara, Reiko Morikawa, Teppei Kuchiba, Aya Lochhead, Paul Yamauchi, Mai Liao, Xiaoyun Imamura, Yu Nosho, Katsuhiko Shima, Kaori Kawachi, Ichiro Qian, Zhi Rong Fuchs, Charles S. Chan, Andrew T. Giovannucci, Edward Ogino, Shuji TI A Prospective Study of Duration of Smoking Cessation and Colorectal Cancer Risk by Epigenetics-related Tumor Classification SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carcinogen; carcinoma; hypermethylation; epigenomics; molecular epidemiology; public health; tobacco; translational epidemiology ID ISLAND METHYLATOR PHENOTYPE; LIFE-STYLE FACTORS; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; POSTMENOPAUSAL HORMONE-THERAPY; DIFFERENTIAL DNA METHYLATION; POPULATION-BASED SAMPLE; BODY-MASS INDEX; CIGARETTE-SMOKING; COLON-CANCER; MICROSATELLITE INSTABILITY AB The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear. Using duplication-method Cox proportional-hazards regression analyses, we examined associations between duration of smoking cessation and colorectal cancer risk according to status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, or DNA methyltransferase-3B (DNMT3B) expression. Follow-up of 134,204 individuals in 2 US nationwide prospective cohorts (Nurses' Health Study (1980-2008) and Health Professionals Follow-up Study (1986-2008)) resulted in 1,260 incident rectal and colon cancers with available molecular data. Compared with current smoking, 10-19, 20-39, and >= 40 years of smoking cessation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ratios (95% confidence intervals) of 0.53 (0.29, 0.95), 0.52 (0.32, 0.85), and 0.50 (0.27, 0.94), respectively (P-trend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (P-trend = 0.25) (P-heterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks). Differential associations between smoking cessation and cancer risks by microsatellite instability (P-heterogeneity = 0.02), DNMT3B expression (P-heterogeneity = 0.03), and BRAF (P-heterogeneity = 0.10) status appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BRAF-mutated cancers. These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer. C1 [Nishihara, Reiko; Morikawa, Teppei; Kuchiba, Aya; Lochhead, Paul; Yamauchi, Mai; Liao, Xiaoyun; Imamura, Yu; Nosho, Katsuhiko; Shima, Kaori; Qian, Zhi Rong; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko; Morikawa, Teppei; Kuchiba, Aya; Lochhead, Paul; Yamauchi, Mai; Liao, Xiaoyun; Imamura, Yu; Nosho, Katsuhiko; Shima, Kaori; Qian, Zhi Rong; Fuchs, Charles S.; Chan, Andrew T.; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Nishihara, Reiko; Kawachi, Ichiro] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. [Nishihara, Reiko; Kuchiba, Aya; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Nishihara, Reiko] Osaka Univ, Div Hlth Sci, Grad Sch Med, Osaka, Japan. [Fuchs, Charles S.; Chan, Andrew T.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Med Oncol,Dept Epidemiol, 450 Brookline Ave,Room JF-215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU US National Institutes of Health [P01 CA87969, P01 CA55075, 1UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993]; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Harvard University Frank Knox Memorial Fellowship FX This work was supported by US National Institutes of Health grants (P01 CA87969; P01 CA55075; 1UM1 CA167552; P50 CA127003 to Charles S. Fuchs; R01 CA137178 to Andrew T. Chan; and R01 CA151993 to Shuji Ogino); and by grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. Andrew T. Chan is a Damon Runyon Clinical Investigator. Paul Lochhead is a Scottish Government Clinical Academic Fellow and was supported by a Harvard University Frank Knox Memorial Fellowship. NR 83 TC 36 Z9 36 U1 1 U2 18 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 JUL 1 PY 2013 VL 178 IS 1 BP 84 EP 100 DI 10.1093/aje/kws431 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 178LL UT WOS:000321449400008 PM 23788674 ER PT J AU Oxford, EC Nguyen, DD Sauk, J Korzenik, JR Yajnik, V Friedman, S Ananthakrishnan, AN AF Oxford, Emily C. Nguyen, Deanna D. Sauk, Jenny Korzenik, Joshua R. Yajnik, Vijay Friedman, Sonia Ananthakrishnan, Ashwin N. TI Impact of Coexistent Celiac Disease on Phenotype and Natural History of Inflammatory Bowel Diseases SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COMPLICATED CROHNS-DISEASE; UNITED-STATES; ASSOCIATION; RISK; POPULATION; PREVALENCE; CLASSIFICATION; METAANALYSIS; ANTIBODIES; PREDICTORS AB OBJECTIVES: Inflammatory bowel disease (IBD) and celiac disease are the two most common immune-mediated gastrointestinal diseases. There is limited knowledge regarding the course of IBD in those with coexisting celiac disease. We conducted this study to determine whether patients with coexisting celiac disease present a unique phenotype of IBD and to examine the frequency of co-occurrence of celiac disease and IBD in comparison with other autoimmune disorders. METHODS: This was a case-control study performed at two tertiary referral centers. Cases comprised of patients with known diagnoses of celiac disease and IBD. Two random IBD controls without celiac disease were selected for each case after matching for IBD type. Disease phenotype and natural history for both Crohn's disease (CD) and ulcerative colitis (UC) were noted from medical record review, and were compared between IBD patients with and without celiac disease. RESULTS: We identified a total of 51 patients with IBD (22 UC, 1 indeterminate colitis, 28 CD) and celiac disease. There was no significant difference in the age, gender, or ethnicity between celiac-IBD and controls. Pancolitis was more common in celiac-UC patients as compared with controls (odds ratio (OR) 3.30, 95% confidence interval (CI) 1.05-21.50). There was also a trend toward increased use of immunomodulators (IMMs) among celiac-UC patients than in non-celiac UC controls (OR 2.83, 95% CI 0.95-8.48). No phenotypic differences were found in celiac-CD patients. There were no significant differences in IBD-related medication usage, hospitalizations, or surgeries. CONCLUSIONS: Patients with UC and celiac disease were more likely to have pancolitis and had a trend toward greater use of IMMs. Coexisting celiac disease did not influence natural history of CD. C1 [Oxford, Emily C.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Korzenik, Joshua R.; Friedman, Sonia] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Nguyen, Deanna D.; Sauk, Jenny; Korzenik, Joshua R.; Yajnik, Vijay; Friedman, Sonia; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health (NIH) [K23 DK097142]; NIH [P30 DK043351]; Procter and Gamble; Warner Chilcott FX A.N. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (NIH) (K23 DK097142). This study is also supported by the NIH (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases.; Joshua R. Korzenik has been a consultant for Procter and Gamble, Shire Pharmaceuticals, CytokinePharma, and receives research support from Procter and Gamble and Warner Chilcott. All other authors declare no conflict of interest. NR 39 TC 19 Z9 19 U1 0 U2 9 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 JUL PY 2013 VL 108 IS 7 BP 1123 EP 1129 DI 10.1038/ajg.2013.20 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 176LG UT WOS:000321305300014 PM 23419379 ER PT J AU Scheiman, JM Dominitz, JA AF Scheiman, James M. Dominitz, Jason A. TI Growth of Ambulatory Surgical Centers, Surgery Volume, and Savings to Medicare SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID ANESTHESIA SERVICES C1 [Scheiman, James M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Tacoma, WA USA. RP Scheiman, JM (reprint author), 3912 Taubman Ct,Box 9362, Ann Arbor, MI 48109 USA. EM jscheima@med.umich.edu OI Dominitz, Jason/0000-0002-8070-7086 NR 4 TC 0 Z9 0 U1 2 U2 4 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 JUL PY 2013 VL 108 IS 7 BP 1175 EP 1176 DI 10.1038/ajg.2013.154 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 176LG UT WOS:000321305300022 PM 23820999 ER PT J AU Young, BA AF Young, Bessie Ann TI Health Literacy in Nephrology: Why Is It Important? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; RECEIVING CHRONIC-HEMODIALYSIS; SYMPTOM MANAGEMENT STRATEGIES; KNOWLEDGE; ASSOCIATIONS; TRIAL; TRANSPLANTATION; PREVALENCE; QUESTIONS; NUMERACY C1 [Young, Bessie Ann] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Young, Bessie Ann] Univ Washington, Seattle, WA 98195 USA. RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst 152 E, 1660 S Columbian Way, Seattle, WA 98108 USA. EM youngb@u.washington.edu NR 38 TC 2 Z9 3 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2013 VL 62 IS 1 BP 3 EP 6 DI 10.1053/j.ajkd.2013.04.003 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 167RZ UT WOS:000320653000004 PM 23773837 ER PT J AU Green, JA Mor, MK Shields, AM Sevick, MA Arnold, RM Palevsky, PM Fine, MJ Weisbord, SD AF Green, Jamie A. Mor, Maria K. Shields, Anne Marie Sevick, Mary Ann Arnold, Robert M. Palevsky, Paul M. Fine, Michael J. Weisbord, Steven D. TI Associations of Health Literacy With Dialysis Adherence and Health Resource Utilization in Patients Receiving Maintenance Hemodialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Health literacy; hemodialysis; outcomes ID MANAGED CARE ENROLLEES; HEART-FAILURE; HOSPITAL ADMISSION; ELDERLY PERSONS; CHRONIC DISEASE; MORTALITY; SKILLS; POPULATION; VALIDATION; KNOWLEDGE AB Background: Although limited health literacy is common in hemodialysis patients, its effects on clinical outcomes are not well understood. Study Design: Observational study. Setting & Participants: 260 maintenance hemodialysis patients enrolled in a randomized clinical trial of symptom management strategies from January 2009 through April 2011. Predictor: Limited health literacy. Outcomes: Dialysis adherence (missed and abbreviated treatments) and health resource utilization (emergency department visits and end-stage renal disease [ESRD]-related hospitalizations). Measurements: We assessed health literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM) and used negative binomial regression to analyze the independent associations of limited health literacy with dialysis adherence and health resource utilization over 12-24 months. Results: 41 of 260 (16%) patients showed limited health literacy (REALM score, <= 60). There were 1,152 missed treatments, 5,127 abbreviated treatments, 552 emergency department visits, and 463 ESRD-related hospitalizations. Limited health literacy was associated independently with an increased incidence of missed dialysis treatments (missed, 0.6% vs 0.3%; adjusted incidence rate ratio [IRR], 2.14; 95% CI, 1.10-4.17), emergency department visits (annual visits, 1.7 vs 1.0; adjusted IRR, 1.37; 95% CI, 1.01-1.86), and hospitalizations related to ESRD (annual hospitalizations, 0.9 vs 0.5; adjusted IRR, 1.55; 95% CI, 1.03-2.34). Limitations: Generalizability and potential for residual confounding. Conclusions: Patients receiving maintenance hemodialysis who have limited health literacy are more likely to miss dialysis treatments, use emergency care, and be hospitalized related to their kidney disease. These findings have important clinical practice and cost implications. Am J Kidney Dis. 62(1):73-80. (C) 2013 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. [Mor, Maria K.; Shields, Anne Marie; Sevick, Mary Ann; Fine, Michael J.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care, Pittsburgh, PA USA. [Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Renal Electrolyte Div, Pittsburgh, PA USA. [Palevsky, Paul M.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Green, JA (reprint author), Geisinger Ctr Hlth Res, 100 N Acad Ave, Danville, PA 17822 USA. EM jgreen1@geisinger.edu OI Palevsky, Paul/0000-0002-7334-5400 FU US Department of Veterans Affairs Health Services Research and Development Service [HSRD IIR 07-190]; Clinical Scientist in Nephrology Fellowship Grant from the American Kidney Fund FX This study was funded by a grant from the US Department of Veterans Affairs Health Services Research and Development Service (Dr Weisbord; HSR&D IIR 07-190) and a Clinical Scientist in Nephrology Fellowship Grant from the American Kidney Fund (Dr Green). The opinions expressed in this article are those of the authors and do not represent the views of the US Department of Veterans Affairs or the US Government. Dr Green completed this study while at the University of Pittsburgh but currently is an employee of Geisinger Medical Center. NR 57 TC 18 Z9 19 U1 8 U2 26 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 JUL PY 2013 VL 62 IS 1 BP 73 EP 80 DI 10.1053/j.ajkd.2012.12.014 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 167RZ UT WOS:000320653000016 PM 23352380 ER PT J AU Skupien, J Warram, JH Groop, PH Krolewski, AS AF Skupien, Jan Warram, James H. Groop, Per-Henrik Krolewski, Andrzej S. TI Cystatin-Based Estimated GFR Versus Creatinine-Based and Creatinine- and Cystatin-Based Estimated GFR for ESRD and Mortality Risk in Diabetes SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; EQUATION; DISEASE; CKD C1 [Skupien, Jan; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Skupien, Jan; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Boston, MA USA. [Skupien, Jan] Jagiellonian Univ, Coll Med, Krakow, Poland. [Groop, Per-Henrik] Folkhalsan Res Ctr, Helsinki, Finland. [Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Helsinki, Finland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU NIDDK NIH HHS [DK41526, DK067638] NR 10 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2013 VL 62 IS 1 BP 184 EP 186 DI 10.1053/j.ajkd.2013.03.029 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 167RZ UT WOS:000320653000034 PM 23684753 ER PT J AU Yonekawa, Y Andreoli, C Miller, JB Loewenstein, JI Sobrin, L Eliott, D Vavvas, DG Miller, JW Kim, IK AF Yonekawa, Yoshihiro Andreoli, Christopher Miller, John B. Loewenstein, John I. Sobrin, Lucia Eliott, Dean Vavvas, Demetrios G. Miller, Joan W. Kim, Ivana K. TI Conversion to Aflibercept For Chronic Refractory Or Recurrent Neovascular Age-Related Macular Degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CHOROIDAL NEOVASCULARIZATION; INTRAVITREAL BEVACIZUMAB; VEGF TRAP; 2.0 MG; RANIBIZUMAB; TACHYPHYLAXIS; THERAPY AB PURPOSE: To explore the visual and anatomic outcomes of patients with refractory or recurrent neovascular age-related macular degeneration (AMD) who were converted from bevacizumab and/or ranibizumab to aflibercept. DESIGN: Two-center, retrospective chart review. METHODS: Treatment history, visual acuity (VA), and central macular thickness (CMT) on spectral-domain optical coherence tomography were collected. Patients were divided into "refractory" (persistent exudation despite monthly injections) or "recurrent" (exudation suppressed, but requiring frequent injections). RESULTS: One hundred and two eyes of 94 patients were included; 68 were refractory and 34 were recurrent. Eyes received a mean of 20.4 prior bevacizumab/ranibizumab injections and a mean of 3.8 aflibercept injections. Mean follow-up was 18 weeks. Mean VA was 20/50-1 before conversion, 20/50-2 after 1 aflibercept injection (P = .723), and 20/50 + 2 after the final injection (P = .253). Subgroup analysis of refractory and recurrent cases also showed stable VA. Of the refractory cases, mean CMT had improved after 1 injection (P < .001) and the final injection (P < .001). Intraretinal (P < .001) and subretinal (P < .001) fluid decreased after 1 injection, and the mean injection interval was extended from 5.2 to 6.2 weeks (P = .003). Of the recurrent cases, mean CMT improved after 1 injection (P < .001) and the final injection (P < .001). Intraretinal (P = .003) and subretinal (P = .046) fluid decreased after 1 injection, and the mean injection interval was extended from 7.2 to 9.5 weeks (P = .001). CONCLUSIONS: Converting patients with chronic neovascular AMD to aflibercept results in stabilized vision and improved anatomic outcomes, while allowing injection intervals to be extended. (C) 2013 by Elsevier Inc. All rights reserved. C1 [Yonekawa, Yoshihiro; Andreoli, Christopher; Miller, John B.; Loewenstein, John I.; Sobrin, Lucia; Eliott, Dean; Vavvas, Demetrios G.; Miller, Joan W.; Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Andreoli, Christopher] Harvard Vanguard Med Associates, Dept Ophthalmol, Retina Serv, Boston, MA USA. RP Kim, IK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM Ivana_Kim@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU Genentech FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. The authors report the following disclosures: D. Eliott: consultant for Acucela, ArcticDx, Genentech, Glaukos, Ophthotech, Regeneron, Salutaris; I.K. Kim: consultant for ArticDx, Sequenom, SalutarisMD, Genzyme, Regeneron, and Genentech, and research support from Genentech; J.W. Miller: board member for Alcon (ended May 2011), consultant for Alcon and KalVista. The Massachusetts Eye and Ear Infirmary has an ownership interest in 3 U.S. patents directed to the use of verteporfin (Quadra Logic Technologies). In addition, the Massachusetts Eye and Ear Infirmary has ownership interest in certain patent applications directed to the selective destruction of subretinal choroidal neovasculature for the treatment of macular degeneration and other disorders. The Massachusetts Eye and Ear Infirmary receives royalties as a result of these patents and patent applications and J.W.M. receives a share of the same in accordance With the Massachusetts Eye and Ear Infirmary's institutional Patent Policy and Procedures, which includes royalty-sharing provisions. The authors indicate no funding support. Contributions of authors: design and conduct of the study (Y.Y., C.A., I.K.K.); collection, management, analysis, and interpretation of data (Y.Y., C.A., J.B.M., J.I.L., L.S., D.E., D.G.V., J.W.M., I.K.K.); and preparation, review, or approval of the manuscript (Y.Y., CA., J.B.M., J.I.L., L.S., D.E., D.G.V., J.W.M., I.K.K.). NR 19 TC 85 Z9 86 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2013 VL 156 IS 1 BP 29 EP 35 DI 10.1016/j.ajo.2013.03.030 PG 7 WC Ophthalmology SC Ophthalmology GA 179OT UT WOS:000321531900006 PM 23668679 ER PT J AU Winterberg, PD Wang, YX Lin, KM Hartono, JR Nagami, GT Zhou, XJ Shelton, JM Richardson, JA Lu, CY AF Winterberg, Pamela D. Wang, Yanxia Lin, Keng-Mean Hartono, John R. Nagami, Glenn T. Zhou, Xin J. Shelton, John M. Richardson, James A. Lu, Christopher Y. TI Reactive oxygen species and IRF1 stimulate IFN alpha production by proximal tubules during ischemic AKI SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE AKI; innate immunity; type I interferon ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; TRANSCRIPTION FACTORS; EPITHELIAL-CELLS; GENE-EXPRESSION; HOSPITALIZED-PATIENTS; OXIDATIVE STRESS; MOUSE KIDNEY; IN-VIVO; INTERFERON AB We previously reported that expression of the transcription factor interferon regulatory factor 1 (IRF1) is an early, critical maladaptive signal expressed by renal tubules during murine ischemic acute kidney injury (AKI). We now show that IRF1 mediates signals from reactive oxygen species (ROS) generated during ischemic AKI and that these signals ultimately result in production of alpha-subtypes of type I interferons (IFN alpha s). We found that genetic knockout of the common type I IFN receptor (IFNARI(-/-)) improved kidney function and histology during AKI. There are major differences in the spatial-temporal production of the two major IFN subtypes, IFN beta and IFN alpha s: IFN beta expression peaks at 4 h, earlier than IFN alpha s, and continues at the same level at 24 h; expression of IFN alpha s also increases at 4 h but continues to increase through 24 h. The magnitude of the increase in IFN alpha s relative to baseline is much greater than that of IFN beta. We show by immunohistology and study of isolated cells that IFN beta is produced by renal leukocytes and IFN alpha s are produced by renal tubules. IRF1, IFN alpha s, and IFNARI were found on the same renal tubules during ischemic AKI. Furthermore, we found that ROS induced IFN alpha expression by renal tubules in vitro. This expression was inhibited by small interfering RNA knockdown of IRF1. Overexpression of IRF1 resulted in the production of IFN alpha s. Furthermore, we found that IFN alpha stimulated production of maladaptive proinflammatory CXCL2 by renal tubular cells. Altogether our data support the following autocrine pathway in renal tubular cells: ROS > IRF1 > IFN alpha > IFNARI > CXCL2. C1 [Winterberg, Pamela D.] Univ Texas SW Med Ctr Dallas, Div Nephrol, Dept Pediat, Dallas, TX 75390 USA. [Wang, Yanxia; Lin, Keng-Mean; Hartono, John R.; Lu, Christopher Y.] Univ Texas SW Med Ctr Dallas, Div Nephrol, Dept Internal Med, Dallas, TX 75390 USA. [Shelton, John M.; Richardson, James A.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dept Internal Med, Dallas, TX 75390 USA. [Zhou, Xin J.; Richardson, James A.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Lu, Christopher Y.] Univ Texas SW Med Ctr Dallas, Grad Sch Biomed Sci Immunol, Dallas, TX 75390 USA. [Nagami, Glenn T.] Vet Affairs Greater Los Angeles, Nephrol Sect, Los Angeles, CA USA. [Nagami, Glenn T.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Lu, CY (reprint author), UT Southwestern Med Ctr, Dept Internal Med, Div Nephrol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM christopher.lu@utsouthwestern.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [RO1-DK-069633, T32-DK-07257, F32-DK-084701]; Beecherl Foundation Grant; Genzyme Nephrology Fellowship; University of Texas Southwestern O'Brien Kidney Research Core Center (National Institute of Diabetes and Digestive and Kidney Diseases) [DK-079328] FX The preceding work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1-DK-069633 and Beecherl Foundation Grant (to C. Y. Lu), National Institute of Diabetes and Digestive and Kidney Diseases Grant T32-DK-07257 (to P. D. Winterberg), National Institute of Diabetes and Digestive and Kidney Diseases Grants F32-DK-084701 and T32-DK-07257 (to J. R. Hartono), a Genzyme Nephrology Fellowship (to Y. Wang), and the University of Texas Southwestern O'Brien Kidney Research Core Center (National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-079328). NR 61 TC 7 Z9 7 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2013 VL 305 IS 2 BP F164 EP F172 DI 10.1152/ajprenal.00487.2012 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 183NI UT WOS:000321822400003 PM 23657854 ER PT J AU Luther, SL Neumayer, L Henderson, WG Foulis, P Richardson, M Haun, J Mikelonis, M Rosen, A AF Luther, Stephen L. Neumayer, Leigh Henderson, William G. Foulis, Phillip Richardson, Matthew Haun, Jolie Mikelonis, Margaret Rosen, Amy TI The use of breast-conserving surgery for women treated for breast cancer in the Department of Veterans Affairs SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Breast cancer; Women; Breast-conserving surgery; Veterans ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; UNITED-STATES; TREATMENT GUIDELINES; RADIATION-THERAPY; 5-YEAR SURVIVAL; CARCINOMA; DISTANCE; RATES; AGE; DIAGNOSIS AB BACKGROUND: Previous non-stage-adjusted research described a lower use of breast-conserving surgery (BCS) for the treatment of breast cancer in the Veterans Health Administration (VHA) facilities than in the private sector. METHODS: We combined data from the VHA Centralized Cancer Registry with administrative datasets to describe surgical treatment for locoregional breast cancer in VHA facilities from 2000 to 2006. RESULTS: When considering only procedures performed in VHA facilities, BCS rates decreased from 50.5% (53/105) in 2000 to 42.3% (n = 58/137) in 2006; however, after accounting for procedures conducted in the private sector and paid for by the VHA, BCS rates approached those experienced in breast cancer patients cared for outside the VHA. CONCLUSIONS: Based solely on procedures performed in the VHA, rates of BCS use are much lower in the VHA than in the private sector. We were able to show similar rates of BCS use when we accounted for procedures paid for by the VHA but performed at an outside facility. Further exploration and prospective analyses to examine these findings are needed. Published by Elsevier Inc. C1 [Luther, Stephen L.; Foulis, Phillip; Richardson, Matthew; Haun, Jolie] James A Haley Vet Hosp, HSR&D RR&D Ctr Excellence Maximizing Rehabil Outc, Tampa, FL 33637 USA. [Neumayer, Leigh] George V Whalen Salt Lake City VA Hlth Care Syst, Salt Lake City, UT USA. [Neumayer, Leigh] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. [Henderson, William G.] Univ Colorado, Dept Biostat & Informat, Sch Publ Hlth, Aurora, CO USA. [Rosen, Amy] VA Boston Healthcare Syst, COLMR, Boston, MA USA. [Rosen, Amy] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Luther, SL (reprint author), James A Haley Vet Hosp, HSR&D RR&D Ctr Excellence Maximizing Rehabil Outc, 8900 Grand Oak Circle, Tampa, FL 33637 USA. EM steve.luther@med.va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IIR 06-053] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development IIR 06-053. NR 33 TC 3 Z9 4 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2013 VL 206 IS 1 BP 72 EP 79 DI 10.1016/j.amjsurg.2012.08.012 PG 8 WC Surgery SC Surgery GA 179HH UT WOS:000321510100012 PM 23611837 ER PT J AU Hu, EK Parrish, C Wrobel, B Deshpande, V Stone, JH AF Hu, Edward K. Parrish, Christopher Wrobel, Bozena Deshpande, Vikram Stone, John H. TI Immunoglobulin G4-related disease presenting as an ethmoid and maxillary mass SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID REGULATORY IMMUNE-REACTIONS; AUTOIMMUNE PANCREATITIS; IGG4-RELATED DISEASE; IGG4; TH2 C1 [Hu, Edward K.; Parrish, Christopher; Wrobel, Bozena] Univ So Calif, Los Angeles, CA 90089 USA. [Deshpande, Vikram; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hu, EK (reprint author), Univ So Calif, Los Angeles, CA 90089 USA. EM edwardkh@usc.edu NR 16 TC 2 Z9 3 U1 0 U2 3 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 JUL PY 2013 VL 111 IS 1 BP 75 EP 77 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 183NT UT WOS:000321823800022 PM 23806471 ER PT J AU Lee, J Shah, K AF Lee, Jarone Shah, Kaushal TI In Patients Presenting With Transient Ischemic Attack, Does the ABCD(2) Clinical Prediction Rule Provide Adequate Risk Stratification for Clinical Decisionmaking in the Emergency Department? SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID STROKE; SCORE C1 [Lee, Jarone] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Shah, Kaushal] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. OI Lee, Jarone/0000-0002-4532-8523 NR 5 TC 1 Z9 1 U1 0 U2 3 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 JUL PY 2013 VL 62 IS 1 BP 14 EP 15 DI 10.1212/WNL.0b013e31825f9d02 PG 2 WC Emergency Medicine SC Emergency Medicine GA 182GS UT WOS:000321730300006 PM 23842051 ER PT J AU Smits, MM Woudstra, P Utzschneider, KM Tong, J Gerchman, F Faulenbach, M Carr, DB Aston-Mourney, K Chait, A Knopp, RH Meigs, JB Boyko, EJ Kahn, SE AF Smits, Mark M. Woudstra, Pier Utzschneider, Kristina M. Tong, Jenny Gerchman, Fernando Faulenbach, Mirjam Carr, Darcy B. Aston-Mourney, Kathryn Chait, Alan Knopp, Robert H. Meigs, James B. Boyko, Edward J. Kahn, Steven E. TI Adipocytokines as features of the metabolic syndrome determined using confirmatory factor analysis SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Metabolic syndrome; Adipokines; Cytokines; Inflammatory proteins; Factor analysis; Obesity; Insulin sensitivity ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; ADIPOSE-TISSUE; OBESITY; RISK; SENSITIVITY; DISEASE; PAI-1; FAT AB Purpose: Confirmatory factor analysis (CFA) was used to test the hypothesis whether adipocytokines are associated with the risk factor cluster that characterizes the metabolic syndrome (MetS). Methods: Data from 134 nondiabetic subjects were analyzed using CFA. Insulin sensitivity (Si) was quantified using intravenous glucose tolerance tests, visceral fat area by computed tomography and fasting high-density lipoprotein, triglycerides, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A (SAA), tumor necrosis factor (TNF)-alpha, adiponectin, resistin, leptin, interleukin (IL)-6, C-reactive protein (CRP), and plasminogen activator inhibitor (PAI)-1 were measured. Results: The basic model representing the MetS included six indicators comprising obesity, SI, lipids, and hypertension, and demonstrated excellent goodness of fit. Using multivariate analysis, MCP-1, SAA, and TNF-alpha were not independently associated with any of the MetS variables. Adiponectin, resistin, leptin, CRP, and IL-6 were associated with at least one of the risk factors, but when added to the basic model decreased all goodness-of-fit parameters. PAI-1 was associated with all cardiometabolic factors and improved goodness-of-fit compared with the basic model. Conclusions: Addition of PAI-1 increased the CFA model goodness of fit compared with the basic model, suggesting that this protein may represent an added feature of the MetS. Published by Elsevier Inc. C1 [Smits, Mark M.; Woudstra, Pier; Utzschneider, Kristina M.; Tong, Jenny; Gerchman, Fernando; Faulenbach, Mirjam; Aston-Mourney, Kathryn; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Smits, Mark M.; Woudstra, Pier; Utzschneider, Kristina M.; Tong, Jenny; Gerchman, Fernando; Faulenbach, Mirjam; Aston-Mourney, Kathryn; Chait, Alan; Knopp, Robert H.; Kahn, Steven E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Carr, Darcy B.] Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Seattle, WA 98195 USA. [Knopp, Robert H.] Univ Washington, Harborview Med Ctr, Northwest Lipid Res Clin, Seattle, WA 98104 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Woudstra, Pier/J-6092-2013; Smits, Mark/E-6573-2014; OI Woudstra, Pier/0000-0002-5870-9923; Smits, Mark/0000-0001-8236-8842; Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn, Steven/0000-0001-7307-9002 FU Medical Research Service of the Department of Veterans Affairs; Egg Nutrition Center; Nutrition Obesity Research Center at the University of Washington [DK-035816]; Diabetes Research Center at the University of Washington [DK-017047]; General Clinical Research Center [RR-000037]; Career Development Award from the American Diabetes Association; NIDDK [DK-080140]; Dutch Diabetes Foundation FX This work was supported by the Medical Research Service of the Department of Veterans Affairs, a grant in aid from the Egg Nutrition Center administered through the US Department of Agriculture, the Nutrition Obesity Research Center at the University of Washington (DK-035816), the Diabetes Research Center at the University of Washington (DK-017047), the General Clinical Research Center (RR-000037), and a generous gift from the Robert B. McMillen Family Trust. J.B.M. was supported by a Career Development Award from the American Diabetes Association and by NIDDK DK-080140. M.M.S and P.W. were medical students participating in an exchange program between Vrije Universiteit University Medical Centre, Amsterdam, The Netherlands, and the University of Washington, Seattle, Washington. P.W. received funding from the Dutch Diabetes Foundation. VA Puget Sound Health Care System provided support for the involvement of Drs. Boyko, Kahn and Utzschneider in this study. NR 44 TC 8 Z9 8 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2013 VL 23 IS 7 BP 415 EP 421 DI 10.1016/j.annepidem.2013.03.001 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 173PC UT WOS:000321090400006 PM 23535025 ER PT J AU Rice, LA Smith, I Kelleher, AR Greenwald, K Hoelmer, C Boninger, ML AF Rice, Laura A. Smith, Ian Kelleher, Annmaire R. Greenwald, Karen Hoelmer, Claire Boninger, Michael L. TI Impact of the Clinical Practice Guideline for Preservation of Upper Limb Function on Transfer Skills of Persons With Acute Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Medical education; Rehabilitation; Spinal cord injuries; Wheelchairs ID WHEELCHAIR USERS SHOULDER; BEARING UPPER EXTREMITY; LONG-TERM PARAPLEGIA; PAIN; IMPLEMENTATION; INDEPENDENCE; IMPINGEMENT; PATIENT AB Objectives: To describe the development of a strict education protocol to implement the clinical practice guideline "Preservation of Upper Limb Function Following Spinal Cord Injury" into a clinical setting, and evaluate the effect of the protocol on transfer quality. Design: Randomized controlled trial. Setting: Acute Model Spinal Cord Injury Systems rehabilitation facility and community. Participants: Volunteer sample of full-time wheelchair users (N=70) with new spinal cord injuries randomized (1:1) to an intervention and standard-of-care group. Intervention: The intervention group was educated on transfer skills with a structured protocol implemented by a physical and occupational therapist who were extensively educated on the clinical practice guidelines and current transfer research. The standard-of-care group received standard therapy services. Main Outcome Measures: Comparison of transfer quality evaluated by the Transfer Assessment Instrument at 4 time points during first year after injury. Results: No significant differences were found between study groups. Secondary analysis based on type of transfer performed found that participants in the intervention group who performed assisted sitting pivot transfers performed higher-quality transfers (mean +/- SE: 9.43 +/-.55) compared with the standard-of-care group (mean +/- SE: 7.81 +/-.46) (P=.026) at 1 year after discharge. Also, participants who performed a dependent transfer had a higher average score across all 4 time points (mean +/- SE: 9.14 +/-.34) compared with the standard-of-care group (mean +/- SE: 8.09 +/-.29) (P=.019). Conclusions: For participants who perform assisted or dependent transfers, use of an evidenced-based, structured education program during acute inpatient rehabilitation has the potential to significantly improve the quality of transfers. Further follow-up testing is necessary with a larger sample size to determine the long-term effects. (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Rice, Laura A.] Univ Illinois, Dept Kinesiol & Community Hlth, Urbana, IL 61801 USA. [Smith, Ian; Greenwald, Karen; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Kelleher, Annmaire R.; Boninger, Michael L.] Univ Pittsburgh, Pittsburgh, PA USA. [Kelleher, Annmaire R.; Hoelmer, Claire; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Hoelmer, Claire; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Rice, LA (reprint author), Huff Hall M-C-586,1206 S 4th St, Champaign, IL 61820 USA. EM ricela@illinois.edu OI Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U.S. Department of Education [H133N000019/H133N060019] FX Supported by the National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, U.S. Department of Education (grant nos. H133N000019/H133N060019). The material presented here is solely the responsibility of the authors and does not necessarily reflect the opinions of the funding agency or the United States Department of Education. NR 29 TC 6 Z9 6 U1 0 U2 11 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 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2013 VL 94 IS 7 BP 1230 EP 1246 DI 10.1016/j.apmr.2013.03.008 PG 17 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 182GG UT WOS:000321729100003 PM 23537608 ER PT J AU Ruhdorfer, A Dannhauer, T Wirth, W Hitzl, W Kwoh, CK Guermazi, A Hunter, DJ Benichou, O Eckstein, F AF Ruhdorfer, Anja Dannhauer, Torben Wirth, Wolfgang Hitzl, Wolfgang Kwoh, C. Kent Guermazi, Ali Hunter, David J. Benichou, Olivier Eckstein, Felix CA Osteoarthritis Initiative TI Thigh Muscle Cross-Sectional Areas and Strength in Advanced Versus Early Painful Osteoarthritis: An Exploratory Between-Knee, Within-Person Comparison in Osteoarthritis Initiative Participants SO ARTHRITIS CARE & RESEARCH LA English DT Article ID MAXIMAL ISOMETRIC STRENGTH; SPACE NARROWING DATA; QUADRICEPS WEAKNESS; CARTILAGE LOSS; ACTIVATION; WOMEN; VOLUME; MEN; ARTHROPLASTY; DISABILITY AB ObjectiveTo compare cross-sectional and longitudinal side differences in thigh muscle anatomic cross-sectional areas (ACSAs), strength, and specific strength (strength/ACSA) between knees with early versus advanced painful radiographic osteoarthritis in the same person. MethodsForty-four of 2,678 Osteoarthritis Initiative participants (31 women and 13 men) met the inclusion criteria of bilateral frequent knee pain, medial joint space narrowing (JSN) in 1 knee, and no medial (or lateral) JSN in the contralateral knee. Thigh muscle ACSAs of the quadriceps, hamstrings, adductors, and individual quadriceps heads at consistent locations were determined using magnetic resonance imaging. Isometric muscle strength was determined in extension/flexion (Good Strength Chair). Baseline quadriceps ACSAs and strength were considered primary end points, and longitudinal changes of these factors were considered secondary end points (by paired t-tests). ResultsNo significant side differences in quadriceps (or other thigh muscle) ACSAs, strength, or specific strength were observed between medial JSN knees versus knees without JSN, or between specific medial JSN knee strata and contralateral knees without JSN, either in men or women. Two-year longitudinal changes in thigh muscle ACSAs and strength were small (5.2%) and did not differ significantly between medial JSN knees and knees without JSN. ConclusionIn the context of previous findings that side differences in pain are associated with side differences in quadriceps ACSAs, the current results suggest that quadriceps (and other thigh muscle) properties are not independently associated with radiographic disease status (JSN) once knees have reached frequent pain status. Further, our longitudinal findings indicate that a more advanced radiographic stage of knee osteoarthritis is not necessarily associated with a longitudinal decline in muscle function. C1 [Ruhdorfer, Anja; Dannhauer, Torben; Wirth, Wolfgang; Hitzl, Wolfgang; Eckstein, Felix] Paracelsus Med Univ, A-5020 Salzburg, Austria. [Dannhauer, Torben; Wirth, Wolfgang; Eckstein, Felix] Chondrometrics, Ainring, Germany. [Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Guermazi, Ali] Boston Univ, Sch Med, Boston, MA 02118 USA. [Guermazi, Ali] Boston Imaging Core Lab LLC, Boston, MA USA. [Hunter, David J.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Hunter, David J.] Univ Sydney, Northern Clin Sch, Sydney, NSW 2006, Australia. [Benichou, Olivier] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Ruhdorfer, A (reprint author), Paracelsus Med Univ, Inst Anat, Strubergasse 21, A-5020 Salzburg, Austria. EM anja.ruhdorfer@pmu.ac.at RI Hitzl, Wolfgang/A-1068-2013; Wirth, Wolfgang/C-8724-2011 OI Wirth, Wolfgang/0000-0002-2297-8283 FU Osteoarthritis Initiative (OAI) [N01-AR-2-2258, N01-AR-22259, N01-AR-2-2260, N01-AR-2-2261, N01-AR-2-2262]; NIH, a branch of the Department of Health and Human Services; Merck Research Laboratories; Novartis Pharmaceuticals Corporation; GlaxoSmithKline; Pfizer Inc.; Paracelsus Medical University Research Fund; Australian Research Council Future Fellowship; Merck Sorono; Genzyme; Novartis; AstraZeneca; Medtronic; Synthes; GSK; Sanofi-Aventis; Abbott; Pfizer FX Image and clinical data acquisition was supported by the Osteoarthritis Initiative (OAI), a public-private partnership comprising 5 contracts (N01-AR-2-2258, N01-AR-22259, N01-AR-2-2260, N01-AR-2-2261, and N01-AR-2-2262) funded by the NIH, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners of the OAI include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer Inc. Private sector funding for the OAI is managed by the Foundation for the NIH. The image analysis was supported by the Paracelsus Medical University Research Fund. Dr. Hunter's work was supported by an Australian Research Council Future Fellowship.; Dr. Wirth has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Merck Sorono, and owns stock and/or stock options in Chondrometrics. Dr. Guermazi has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Genzyme, Novartis, and AstraZeneca and (more than $10,000) from Merck Sorono, and owns stock and/or stock options in Boston Imaging Core Lab LLC. Dr. Benichou owns stock and/or stock options in Eli Lilly. Dr. Eckstein has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Medtronic, Synthes, GSK, and Genzyme and (more than $10,000 each) from Merck Sorono, Sanofi-Aventis, Novartis, Abbott, and Pfizer, and owns stock and/or stock options in Chondrometrics. NR 40 TC 18 Z9 18 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUL PY 2013 VL 65 IS 7 BP 1034 EP 1042 DI 10.1002/acr.21965 PG 9 WC Rheumatology SC Rheumatology GA 174VF UT WOS:000321184000004 PM 23401316 ER PT J AU Singh, JA Kwoh, CK Richardson, D Chen, W Ibrahim, SA AF Singh, Jasvinder A. Kwoh, C. Kent Richardson, Diane Chen, Wei Ibrahim, Said A. TI Sex and Surgical Outcomes and Mortality After Primary Total Knee Arthroplasty: A Risk-Adjusted Analysis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID MYOCARDIAL-INFARCTION MORTALITY; STATES MEDICARE POPULATION; IN-HOSPITAL COMPLICATIONS; UNITED-STATES; TOTAL HIP; JOINT ARTHROPLASTY; RIGHT TOOL; APR-DRGS; REPLACEMENT; GENDER AB ObjectiveTotal knee arthroplasty (TKA) is a widely utilized and effective treatment option for end-stage knee osteoarthritis (OA). Knee OA is more prevalent among women compared to men, but there are limited data on the sex differences in surgical outcomes after primary TKA. MethodsOur sample consisted of all primary TKAs performed in Pennsylvania during the fiscal year 2002. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify major complications and surgical revision. We used mixed-effects logistic regression models to examine the associations between sex and all-cause mortality, readmissions, and major surgical complications. We used proportional hazards models to assess the risk of surgical revision after index arthroplasty. We adjusted for race, age, hospital teaching status, hospital procedure volume, insurance status, and risk of mortality. ResultsIn 17,994 primary TKAs, there were 46 and 220 deaths at 30 days and 1 year, respectively. Compared to women, men had higher adjusted odds of 1-year mortality (odds ratio [OR] 1.48 [95% confidence interval (95% CI) 1.13-1.94]) after primary TKA. The overall odds of most major 30-day complications did not differ by sex except for surgical wound infections, which were higher in men compared to women (OR 1.31 [95% CI 1.08-1.60]); 30-day readmission was higher in men (OR 1.25 [95% CI 1.10-1.43]). Men had significantly higher rates of revision of index knee arthroplasty at 5 years (hazard ratio 1.20 [95% CI 1.05-1.36]) compared to women. ConclusionThe higher rates of mortality, hospital readmissions, revision surgery, and wound infections in men undergoing elective primary TKA compared to women indicate there is a sex disparity in these outcomes. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA. [Kwoh, C. Kent; Richardson, Diane; Chen, Wei] VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Kwoh, C. Kent; Richardson, Diane; Chen, Wei] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kwoh, C. Kent; Richardson, Diane; Chen, Wei; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off, Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Arthritis Foundation, Western Pennsylvania Chapter; National Institute on Aging, National Cancer Institute; Agency for Healthcare Research and Quality Centers for Education & Research on Therapeutics; Birmingham VA Medical Center, Alabama; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24-AR-055259]; Allergan; Novartis; Regeneron; Saviant; URL; Areda; Takeda FX Supported by a pilot grant from the Arthritis Foundation, Western Pennsylvania Chapter. Dr. Singh's work was supported by the National Institute on Aging, National Cancer Institute, Agency for Healthcare Research and Quality Centers for Education & Research on Therapeutics, and Birmingham VA Medical Center, Alabama. Dr. Ibrahim's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant K24-AR-055259).; Dr. Singh has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Allergan, Novartis, Regeneron, Saviant, and URL, and (more than $10,000 each) from Areda and Takeda. NR 37 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUL PY 2013 VL 65 IS 7 BP 1095 EP 1102 DI 10.1002/acr.21953 PG 8 WC Rheumatology SC Rheumatology GA 174VF UT WOS:000321184000011 PM 23335560 ER PT J AU Vina, ER Cloonan, YK Ibrahim, SA Hannon, MJ Boudreau, RM Kwoh, CK AF Vina, Ernest R. Cloonan, Yona K. Ibrahim, Said A. Hannon, Michael J. Boudreau, Robert M. Kwoh, C. Kent TI Race, Sex, and Total Knee Replacement Consideration: Role of Social Support SO ARTHRITIS CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; OLDER-ADULTS; JOINT REPLACEMENT; AFRICAN-AMERICAN; PSYCHOSOCIAL FACTORS; DEPRESSIVE SYMPTOMS; PATIENT PREFERENCES; RACIAL-DIFFERENCES; OSTEO-ARTHRITIS; HEALTH AB ObjectiveTo determine whether there are racial differences in social support among patients with knee osteoarthritis (OA) and whether the impact of social support on patient preferences for total knee replacement (TKR) varies by race and sex. MethodsA total of 514 white and 285 African American patients with knee OA were surveyed. Logistic regression models were performed to determine if the relationship between willingness to undergo TKR and the interaction of patient race and sex was mediated by social support. ResultsCompared to whites with knee OA, African American patients were less likely to be married (P < 0.001), reported less close friends/relatives (P < 0.001), and had lower Medical Outcomes Study Social Support Scale (MOS-SSS) scores (P < 0.001). African American patients were also less willing to undergo TKR (62% versus 80%; P < 0.001) than whites. The odds of willingness to undergo TKR were less in white females compared to white males when adjusted for recruitment site, age, income, and the Western Ontario and McMaster Universities Osteoarthritis Index score (odds ratio [OR] 0.57, 95% confidence interval [95% CI] 0.34-0.96). This difference was no longer significant when further adjusted for marital status, number of close friends/relatives, and MOS-SSS score, but the effect size remained unchanged (OR 0.60, 95% CI 0.35-1.02). The odds of willingness to undergo TKR remained much less in African American females (OR 0.35, 95% CI 0.19-0.64) and African American males (OR 0.28, 95% CI 0.14-0.54) compared to white males when controlled for sociodemographic, clinical, and social support measures. ConclusionAfrican American patients reported less structural and functional social support than whites. Social support is an important determinant of preference for TKR surgery only among whites. C1 [Vina, Ernest R.; Cloonan, Yona K.; Hannon, Michael J.; Boudreau, Robert M.; Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Vina, Ernest R.; Kwoh, C. Kent] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Philadelphia, PA 19104 USA. RP Vina, ER (reprint author), Arthrit Res Ctr, 3347 Forbes Ave,Suite 220, Pittsburgh, PA 15213 USA. EM evina1@pitt.edu OI Boudreau, Robert/0000-0003-0162-5187; Cloonan, Yona/0000-0003-3893-3693; Vina, Ernest/0000-0001-8135-1731 FU NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60-AR-054731, AR-055259] FX Supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant P60-AR-054731). Dr. Ibrahim's work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases K24 Award (grant AR-055259). NR 52 TC 9 Z9 9 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUL PY 2013 VL 65 IS 7 BP 1103 EP 1111 DI 10.1002/acr.21925 PG 9 WC Rheumatology SC Rheumatology GA 174VF UT WOS:000321184000012 PM 23281259 ER PT J AU Lee, LJ Damato, AL Viswanathan, AN AF Lee, Larissa J. Damato, Antonio L. Viswanathan, Akila N. TI Clinical outcomes of high-dose-rate interstitial gynecologic brachytherapy using real-time CT guidance SO BRACHYTHERAPY LA English DT Article DE Gynecologic brachytherapy; High-dose-rate brachytherapy; Interstitial brachytherapy; Image-guided brachytherapy ID MAGNETIC-RESONANCE; VAGINAL-CANCER; CERVIX CANCER; MALIGNANCIES; LAPAROSCOPY; LAPAROTOMY; IMPLANTS AB PURPOSE: To evaluate clinical outcomes of CT-guided high-dose-rate (HDR) interstitial brachy-therapy for primary and recurrent gynecologic cancer. METHODS AND MATERIALS: Records were reviewed for 68 women (34 with primary disease and 34 with recurrence) treated with CT-guided HDR interstitial brachytherapy between May 2005 and September 2011. Interstitial application was performed under general anesthesia using an iterative approach of catheter insertion and adjustment with serial image acquisition by CT in a dedicated brachytherapy suite. The median fractional brachytherapy dose was 3.9 Gy delivered twice daily in seven fractions. The median cumulative dose in equivalent 2-Gy fractions was 74.8 Gy. Actuarial survival estimates were calculated using the Kaplan-Meier method, and toxicity was reported by Common Toxicity Criteria. RESULTS: Primary disease sites were endometrial (34), cervical (17), vaginal (11), ovarian (3), and vulvar (3). Median age was 61.5 years, and tumor size at diagnosis was 3.4 cm. Median D-90 and V-100 were 73.6 Gy and 87.5%, respectively; median D-2cc for bladder, rectum, and sigmoid were 67.1, 64.6, and 53.7 Gy, respectively. With a median followup of 17 months, actuarial rates of local control, progression-free survival, and overall survival at 2 years for all patients were 86%, 60%, and 64%, respectively. There were 9 grade 3 late toxicities (six gastrointestinal and three vulvovaginal). CONCLUSIONS: HDR interstitial brachytherapy with CT-guided catheter placement results in acceptable local control, toxicity, and survival rates for women with primary or recurrent gynecologic cancer. Durable pelvic control may be achieved in most patients with this specialized brachytherapy technique. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 20 TC 27 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JUL-AUG PY 2013 VL 12 IS 4 BP 303 EP 310 DI 10.1016/j.brachy.2012.11.002 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 179ND UT WOS:000321526200005 PM 23491023 ER PT J AU Maleki, N Becerra, L Brawn, J McEwen, B Burstein, R Borsook, D AF Maleki, Nasim Becerra, Lino Brawn, Jennifer McEwen, Bruce Burstein, Rami Borsook, David TI Common hippocampal structural and functional changes in migraine SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Headache; Pain; Migraine; fMRI; Functional connectivity; Morphometry ID GREY-MATTER VOLUME; SPREADING DEPRESSION; PSYCHOLOGICAL TRAUMA; PREFRONTAL CORTEX; ALZHEIMER-DISEASE; STRESS MEDIATORS; NEUROPATHIC PAIN; THERMAL STIMULI; HUMAN BRAIN; ATROPHY AB The hippocampus is classically involved in memory consolidation, spatial navigation and is involved in the stress response. Migraine is an episodic disorder characterized by intermittent attacks with a number of physiological and emotional stressors associated with or provoking each attack. Given that migraine attacks can be viewed as repeated stressors, alterations in hippocampal function and structure may play an important role in migraine pathophysiology. Using high-resolution magnetic resonance imaging, hippocampal morphometric and functional differences (in response to noxious heat stimulation) were compared in age and gender-matched acute episodic migraineurs with high (HF) versus low (LF) frequency of migraine attacks. Morphometric results were compared with age and gender-matched healthy control (HC) cohort. Significant larger bilateral hippocampal volume was found in LF group relative to the HF and HC groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency. Functional correlates of greater deactivation (LF > HF) in the same hippocampal regions in response to noxious stimulation was also accompanied by overall reduction in functional connectivity of the hippocampus with other brain regions involved in pain processing in the HF group. The results implicate involvement of hippocampus in the pathophysiology of the migraine. C1 [Maleki, Nasim; Becerra, Lino; Brawn, Jennifer; Borsook, David] MGH, MCL, Ctr Pain & Brain, Dept Anesthesia, Boston, MA USA. [Maleki, Nasim; Becerra, Lino; Brawn, Jennifer; Borsook, David] MGH, MCL, Ctr Pain & Brain, Dept Radiol, Boston, MA USA. [Maleki, Nasim; Becerra, Lino; Brawn, Jennifer; Borsook, David] CHB, Boston, MA USA. [Maleki, Nasim; Becerra, Lino; Brawn, Jennifer; Borsook, David] Harvard Univ, Sch Med, Boston, MA USA. [Becerra, Lino; Borsook, David] McLean Hosp, Dept Psychiat, PAIN Grp, Belmont, MA 02178 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Becerra, Lino; Borsook, David] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [McEwen, Bruce] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. [Burstein, Rami] Harvard Univ, Sch Med, Dept Anesthesia, Beth Israel Deaconess Hosp, Boston, MA 02115 USA. RP Borsook, D (reprint author), MGH, MCL, Ctr Pain & Brain, Dept Anesthesia, Boston, MA USA. EM david.borsook@childrens.harvard.edu FU NIH (NINDS) [K24 NS064050, R01 NS056195, R01-NS073997]; Merck and Co. FX The work was supported in by grants from NIH (K24 NS064050 (NINDS) and R01 NS056195 (NINDS) and R01-NS073997 (NINDS) to DB) and an Investigator Initiated Grant from Merck and Co. NR 73 TC 41 Z9 45 U1 1 U2 18 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUL PY 2013 VL 218 IS 4 BP 903 EP 912 DI 10.1007/s00429-012-0437-y PG 10 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 173GT UT WOS:000321067200006 PM 22760159 ER PT J AU Makris, N Preti, MG Asami, T Pelavin, P Campbell, B Papadimitriou, GM Kaiser, J Baselli, G Westin, CF Shenton, ME Kubicki, M AF Makris, N. Preti, M. G. Asami, T. Pelavin, P. Campbell, B. Papadimitriou, G. M. Kaiser, J. Baselli, G. Westin, C. F. Shenton, M. E. Kubicki, M. TI Human middle longitudinal fascicle: variations in patterns of anatomical connections SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Diffusion tensor tractography; Middle longitudinal fascicle; Angular gyrus; Superior parietal lobule; Superior temporal gyrus; Language ID SUPERIOR TEMPORAL SULCUS; WHITE-MATTER; IN-VIVO; RHESUS-MONKEY; HUMAN BRAIN; DT-MRI; TOPOGRAPHIC PARCELLATION; DIFFUSION TRACTOGRAPHY; ARCUATE FASCICULUS; SPEECH-PERCEPTION AB Based on high-resolution diffusion tensor magnetic resonance imaging (DTI) tractographic analyses in 39 healthy adult subjects, we derived patterns of connections and measures of volume and biophysical parameters, such as fractional anisotropy (FA) for the human middle longitudinal fascicle (MdLF). Compared to previous studies, we found that the cortical connections of the MdLF in humans appear to go beyond the superior temporal (STG) and angular (AG) gyri, extending to the temporal pole (TP), superior parietal lobule (SPL), supramarginal gyrus, precuneus and the occipital lobe (including the cuneus and lateral occipital areas). Importantly, the MdLF showed a striking lateralized pattern with predominant connections between the TP, STG and AG on the left and TP, STG and SPL on the right hemisphere. In light of the results of the present study, and of the known functional role of the cortical areas interconnected by the MdLF, we suggested that this fiber pathway might be related to language, high order auditory association, visuospatial and attention functions. C1 [Makris, N.; Campbell, B.; Papadimitriou, G. M.; Kaiser, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Ctr Morphometr Anal,A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Makris, N.; Campbell, B.; Papadimitriou, G. M.; Kaiser, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Ctr Morphometr Anal,A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Makris, N.; Campbell, B.; Papadimitriou, G. M.; Kaiser, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol Serv, Ctr Morphometr Anal,A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Makris, N.; Asami, T.; Pelavin, P.; Shenton, M. E.; Kubicki, M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02115 USA. [Makris, N.] Boston Univ, Dept Anat & Neurobiol, Sch Med, Boston, MA 02215 USA. [Preti, M. G.; Baselli, G.] Politecn Milan, Dept Bioengn, I-20133 Milan, Italy. [Preti, M. G.] Fdn Don C Gnocchi, Magnet Resonance Lab, Milan, Italy. [Westin, C. F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Math Imaging,Surg Planning Lab,MRI Div,Dept R, Boston, MA 02115 USA. [Shenton, M. E.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Lab Neurosci,Clin Neurosci Div,Dept Psychiat,Broc, Brockton, MA 02401 USA. RP Makris, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Ctr Morphometr Anal,A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM nikos@cma.mgh.harvard.edu FU NIDA [1R01DA027804-01]; NIMH [1R21MH084041-01A1]; National Institute of Health [K05 MH070047, R01 MH 50740, P50MH 080272-CIDAR, R01 M074794]; Department of Veterans Affairs Merit Award; VA Schizophrenia Center Grant; National Alliance for Medical Image Computing (NA-MIC); National Institutes of Health Roadmap for Medical Research [U54 EB005149]; Progetto Roberto Rocca Foundation FX This study was supported, in part, by grants from: NIDA 1R01DA027804-01, NIMH 1R21MH084041-01A1 (NM); the National Institute of Health (K05 MH070047 and R01 MH 50740 to MES, P50MH 080272-CIDAR award-to MES and MK, R01 M074794 to CFW and MK), the Department of Veterans Affairs Merit Award (MES), the VA Schizophrenia Center Grant (MES); the National Alliance for Medical Image Computing (NA-MIC), the latter a grant supported through the National Institutes of Health Roadmap for Medical Research, Grant U54 EB005149 (MK, MES, CFW); Progetto Roberto Rocca Foundation (MGP) NR 73 TC 16 Z9 16 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUL PY 2013 VL 218 IS 4 BP 951 EP 968 DI 10.1007/s00429-012-0441-2 PG 18 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 173GT UT WOS:000321067200010 PM 22782432 ER PT J AU Melcher, JR AF Melcher, Jennifer R. TI Comment on Schecklmann et al.: a call to consider both "negative" and "positive" results in brain research on tinnitus SO BRAIN STRUCTURE & FUNCTION LA English DT Letter C1 [Melcher, Jennifer R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Melcher, Jennifer R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Melcher, JR (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM jennifer_melcher@meei.harvard.edu NR 1 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUL PY 2013 VL 218 IS 4 BP 1071 EP 1071 DI 10.1007/s00429-013-0567-x PG 1 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 173GT UT WOS:000321067200017 PM 23639995 ER PT J AU Russo, AL Taghian, AG AF Russo, Andrea L. Taghian, Alphonse G. TI Fat necrosis of the breast in the accelerated partial breast irradiation era: the need for a universal grading system SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Fat necrosis; Breast cancer; Partial breast irradiation ID RATE INTERSTITIAL BRACHYTHERAPY; DOSE-RATE BRACHYTHERAPY; SONOGRAPHIC FEATURES; CONSERVING THERAPY; RADIATION-THERAPY; PROSPECTIVE TRIAL; RANDOMIZED-TRIAL; PHASE-I/II; FOLLOW-UP; CANCER AB Fat necrosis of the breast is increasingly reported and used as a trial endpoint in the treatment of breast cancer with accelerated partial breast irradiation (APBI). Yet, there is no universal toxicity scoring system within the latest version of the Common Terminology Criteria for Adverse Events (CTCAE v4.0). This requires investigators to adopt their own scoring system or improperly use those that exist, and limits accurate reporting of this entity. Fat necrosis of the breast also creates diagnostic uncertainty among clinicians and concern of recurrence among patients. In this review, we address the question of increasing incidence of fat necrosis through the comparison of recent APBI trials and literature. The pathogenesis, symptoms, clinical and radiologic diagnosis, clinical predictors of developing fat necrosis, management and follow-up are also discussed. Lastly, we propose a simplified and universal scoring system for the reporting of fat necrosis. C1 [Russo, Andrea L.] Harvard Radiat Oncol Program, Boston, MA USA. [Taghian, Alphonse G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 45 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2013 VL 140 IS 1 BP 1 EP 11 DI 10.1007/s10549-013-2611-1 PG 11 WC Oncology SC Oncology GA 180JB UT WOS:000321588900001 PM 23797180 ER PT J AU O'Toole, J Miller, CL Specht, MC Skolny, MN Jammallo, LS Horick, N Elliott, K Niemierko, A Taghian, AG AF O'Toole, Jean Miller, Cynthia L. Specht, Michelle C. Skolny, Melissa N. Jammallo, Lauren S. Horick, Nora Elliott, Krista Niemierko, Andrzej Taghian, Alphonse G. TI Cording following treatment for breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Cording; Axillary web syndrome; Functional impairment; Lymphedema; Quality of life; Breast surgery ID AXILLARY WEB SYNDROME; LYMPHEDEMA; SURGERY; PHYSIOTHERAPY; CONSERVATION; DISSECTION; SURVIVORS; DISEASE; RISK AB Treatment for breast cancer may result in the formation of palpable cords in the axillary region. Our aim was to evaluate cording incidence, risk factors, and association with upper extremity functional impairment and measured arm volume change. We included 308 patients with unilateral breast cancer prospectively screened for upper extremity lymphedema, symptoms and function. Patients were assessed pre- and post-operatively and at 3-8-month intervals with perometer arm measurements and the LEFT-BC questionnaire. Cording was determined by patient self-report. The cumulative incidence of cording and its association with clinicopathologic factors, upper extremity functional impairment, and measured arm volume change were analyzed. 31.5 % (97/308) of patients reported cording, with a cumulative incidence of 36.2 % at 24 months post-operative. Clinicopathologic factors significantly associated with cording by multivariate analysis included axillary lymph node dissection (p < 0.0001) and younger age at diagnosis (p = 0.0005). Cording was associated with increased functional impairment (p = 0.0018) and an arm volume increase of a parts per thousand yen5 % (p = 0.028). Cording following breast cancer treatment is common, and may occur beyond the post-operative period. Our findings emphasize the importance of identifying patients at high risk for cording, and developing strategies to minimize functional impairment and arm volume elevation associated with cording. Future studies should investigate the effectiveness of interventions for cording following breast cancer treatment. C1 [O'Toole, Jean] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Miller, Cynthia L.; Skolny, Melissa N.; Jammallo, Lauren S.; Niemierko, Andrzej; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Specht, Michelle C.; Elliott, Krista] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Horick, Nora] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118, P50CA089393] FX This project was supported by Award R01CA139118 (AGT) and Award P50CA089393 (AGT) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institutes of Health. NR 29 TC 7 Z9 7 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2013 VL 140 IS 1 BP 105 EP 111 DI 10.1007/s10549-013-2616-9 PG 7 WC Oncology SC Oncology GA 180JB UT WOS:000321588900010 PM 23813304 ER PT J AU Chipman, J Drohan, B Blackford, A Parmigiani, G Hughes, K Bosinoff, P AF Chipman, Jonathan Drohan, Brian Blackford, Amanda Parmigiani, Giovanni Hughes, Kevin Bosinoff, Phil TI Providing access to risk prediction tools via the HL7 XML-formatted risk web service SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Risk prediction; BayesMendel; BRCAPRO; IBIS Breast Cancer Risk Evaluation Tool; Colorectal Cancer Risk Assessment Tool; Web service; Risk service ID CARRIER PROBABILITY ESTIMATION; BREAST-CANCER RISK; BRCA2 MUTATIONS; FAMILY-HISTORY; WOMEN; MODEL; SUSCEPTIBILITY; MARKERS AB Cancer risk prediction tools provide valuable information to clinicians but remain computationally challenging. Many clinics find that CaGene or HughesRiskApps fit their needs for easy- and ready-to-use software to obtain cancer risks; however, these resources may not fit all clinics' needs. The HughesRiskApps Group and BayesMendel Lab therefore developed a web service, called "Risk Service", which may be integrated into any client software to quickly obtain standardized and up-to-date risk predictions for BayesMendel tools (BRCAPRO, MMRpro, PancPRO, and MelaPRO), the Tyrer-Cuzick IBIS Breast Cancer Risk Evaluation Tool, and the Colorectal Cancer Risk Assessment Tool. Software clients that can convert their local structured data into the HL7 XML-formatted family and clinical patient history (Pedigree model) may integrate with the Risk Service. The Risk Service uses Apache Tomcat and Apache Axis2 technologies to provide an all Java web service. The software client sends HL7 XML information containing anonymized family and clinical history to a Dana-Farber Cancer Institute (DFCI) server, where it is parsed, interpreted, and processed by multiple risk tools. The Risk Service then formats the results into an HL7 style message and returns the risk predictions to the originating software client. Upon consent, users may allow DFCI to maintain the data for future research. The Risk Service implementation is exemplified through HughesRiskApps. The Risk Service broadens the availability of valuable, up-to-date cancer risk tools and allows clinics and researchers to integrate risk prediction tools into their own software interface designed for their needs. Each software package can collect risk data using its own interface, and display the results using its own interface, while using a central, up-to-date risk calculator. This allows users to choose from multiple interfaces while always getting the latest risk calculations. Consenting users contribute their data for future research, thus building a rich multicenter resource. C1 [Chipman, Jonathan; Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Drohan, Brian; Hughes, Kevin; Bosinoff, Phil] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blackford, Amanda] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. RP Chipman, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM chipmanj@jimmy.harvard.edu OI Hughes, Kevin/0000-0003-4084-6484 FU Susan G. Komen Foundation; NCI [2 P30 CA006516-47] FX Work partly supported by the Susan G. Komen Foundation and by NCI award 2 P30 CA006516-47 (DF/HCC comprehensive cancer center core grant). NR 19 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2013 VL 140 IS 1 BP 187 EP 193 DI 10.1007/s10549-013-2605-z PG 7 WC Oncology SC Oncology GA 180JB UT WOS:000321588900018 PM 23793601 ER PT J AU Green, JS Norris, DA Wisell, J AF Green, J. S. Norris, D. A. Wisell, J. TI Novel cutaneous effects of combination chemotherapy with BRAF and MEK inhibitors: a report of two cases SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID METASTATIC MELANOMA; MELANOCYTIC NEVI; RAF INHIBITORS; HALO NEVI; VEMURAFENIB; SORAFENIB; MUTATIONS; THERAPY; REGRESSION; INFILTRATE AB The discovery that some melanoma tumours harbour mutations in the BRAF gene (e.g. V600E) and the subsequent development of specific BRAF inhibitors have greatly improved the treatment of metastatic melanoma. Resistance of tumour cells to BRAF inhibitors is reduced by the addition of an MEK inhibitor; both BRAF and MEK inhibitors have been reported to produce a variety of dermatological toxic effects. Benign naevi often harbour BRAF mutations but few reports exist that document the response of naevus cells to BRAF inhibition. We report sarcoidal-type granulomatous inflammation in two patients with metastatic melanoma undergoing treatment with combination BRAF and MEK inhibitor therapy. This inflammation manifested in one patient as a nonspecific papular eruption; in the other, in association with clinical regression of multiple benign-appearing naevi during the course of therapy. The significance of sarcoidal-type inflammation occurring during treatment of metastatic melanoma with a combination of BRAF and MEK inhibitors is unclear. Its association with the clinical regression of benign-appearing naevi suggests a possible exaggerated inflammatory response to degenerating naevus cells in these lesions. C1 [Green, J. S.; Norris, D. A.; Wisell, J.] Univ Colorado Denver, Dept Dermatol, Aurora, CO 80011 USA. [Wisell, J.] Univ Colorado Denver, Dept Pathol, Aurora, CO 80011 USA. [Norris, D. A.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Green, JS (reprint author), Univ Colorado Denver, Dept Dermatol, Anschutz Med Campus,1665 Aurora Court,Mail Stop F, Aurora, CO 80011 USA. EM julie.green@ucdenver.edu NR 28 TC 7 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUL PY 2013 VL 169 IS 1 BP 172 EP 176 DI 10.1111/bjd.12279 PG 5 WC Dermatology SC Dermatology GA 178HK UT WOS:000321436900030 PM 23413975 ER PT J AU Gatt, ME Takada, K Mani, M Lerner, M Pick, M Hideshima, T Carrasco, DE Protopopov, A Ivanova, E Sangfelt, O Grander, D Barlogie, B Shaughnessy, JD Anderson, KC Carrasco, DR AF Gatt, Moshe E. Takada, Kohichi Mani, Mala Lerner, Mikael Pick, Marjorie Hideshima, Teru Carrasco, Daniel E. Protopopov, Alexei Ivanova, Elena Sangfelt, Olle Grander, Dan Barlogie, Bart Shaughnessy, John D., Jr. Anderson, Kenneth C. Carrasco, Daniel R. TI TRIM13 (RFP2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF Kappa B pathway and proteasome activity SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE TRIM13 (RFP2); 13q; myeloma; proliferation; proteasome ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHROMOSOME-13 DELETION; DISEASE PROGRESSION; PROSTATE-CANCER; NUCLEAR EXPORT; ER STRESS; 13Q14; APOPTOSIS; GENES; ALPHA AB Multiple myeloma (MM) is an incurable neoplasm caused by proliferation of malignant plasma cells in the bone marrow (BM). MM is characterized frequently by a complete or partial deletion of chromosome 13q14, seen in more than 50% of patients at diagnosis. Within this deleted region the tripartite motif containing 13 (TRIM13, also termed RFP2) gene product has been proposed to be a tumour suppressor gene (TSG). Here, we show that low expression levels of TRIM13 in MM are associated with chromosome 13q deletion and poor clinical outcome. We present a functional analysis of TRIM13 using a loss-of-function approach, and demonstrate that TRIM13 downregulation decreases tumour cell survival as well as cell cycle progression and proliferation of MM cells. In addition, we provide evidence for the involvement of TRIM13 downregulation in inhibiting the NF kappa B pathway and the activity of the 20S proteasome. Although this data does not support a role of TRIM13 as a TSG, it substantiates important roles of TRIM13 in MM tumour survival and proliferation, underscoring its potential role as a novel target for therapeutic intervention. C1 [Gatt, Moshe E.; Takada, Kohichi; Mani, Mala; Hideshima, Teru; Carrasco, Daniel E.; Protopopov, Alexei; Ivanova, Elena; Anderson, Kenneth C.; Carrasco, Daniel R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gatt, Moshe E.; Pick, Marjorie] Hadassah Hebrew Univ, Med Ctr, Dept Haematol, Jerusalem, Israel. [Takada, Kohichi] Sapporo Med Univ, Sch Med, Dept Internal Med 4, Sapporo, Hokkaido, Japan. [Lerner, Mikael; Sangfelt, Olle; Grander, Dan] Karolinska Inst, Canc Ctr Karolinska, Dept Pathol & Oncol, Stockholm, Sweden. [Lerner, Mikael; Sangfelt, Olle; Grander, Dan] Karolinska Univ Hosp, Stockholm, Sweden. [Hideshima, Teru; Protopopov, Alexei; Ivanova, Elena; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Barlogie, Bart; Shaughnessy, John D., Jr.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. [Carrasco, Daniel R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Carrasco, DR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ruben_carrasco@dfci.harvard.edu FU American Physician Foundation for Israel; MMRF; Swedish Research Council; Swedish Cancer Society; Cancer Research Funds of Radiumhemmet; King Gustaf V Jubilee Fund; NIH [RO CA127435, PO CA78378] FX We thank Dr William Hahn (DFCI, RNAi Consortium (TRC) at the Broad Institute) for lentiviral shRNA vectors. Financial support: M.E.G. is supported by the American Physician Foundation for Israel. D.R.C is supported by MMRF, Senior Research Award and Claudia Barr Award; M.L, O.S and D.G are supported by the Swedish Research Council, the Swedish Cancer Society, the Cancer Research Funds of Radiumhemmet and King Gustaf V Jubilee Fund.; K.C.A is supported by NIH grants RO CA127435, PO CA78378. NR 45 TC 3 Z9 4 U1 0 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 JUL PY 2013 VL 162 IS 2 BP 210 EP 220 DI 10.1111/bjh.12365 PG 11 WC Hematology SC Hematology GA 175DU UT WOS:000321211300008 PM 23647456 ER PT J AU Peteet, JR Balboni, MJ AF Peteet, John R. Balboni, Michael J. TI Spirituality and religion in oncology SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article DE supportive care; psychological; behavioral oncology; complementary; alternative; and integrative medicine; religion; spirituality ID QUALITY-OF-LIFE; ADVANCED CANCER-PATIENTS; RANDOMIZED CONTROLLED-TRIAL; STRESS REDUCTION MBSR; BREAST-CANCER; PROSTATE-CANCER; PALLIATIVE CARE; US PHYSICIANS; ALTERNATIVE MEDICINE; NEEDS-ASSESSMENT AB Despite the difficulty in clearly defining and measuring spirituality, a growing literature describes its importance in oncology and survivorship. Religious/spiritual beliefs influence patients' decision-making with respect to both complementary therapies and aggressive care at the end of life. Measures of spirituality and spiritual well-being correlate with quality of life in cancer patients, cancer survivors, and caregivers. Spiritual needs, reflective of existential concerns in several domains, are a source of significant distress, and care for these needs has been correlated with better psychological and spiritual adjustment as well as with less aggressive care at the end of life. Studies show that while clinicians such as nurses and physicians regard some spiritual care as an appropriate aspect of their role, patients report that they provide it infrequently. Many clinicians report that their religious/spiritual beliefs influence their practice, and practices such as mindfulness have been shown to enhance clinician self-care and equanimity. Challenges remain in the areas of conceptualizing and measuring spirituality, developing and implementing training for spiritual care, and coordinating and partnering with chaplains and religious communities. CA Cancer J Clin 2013;63:280-289. ((c))2013 American Cancer Society. C1 [Peteet, John R.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Adult Psychosocial Oncol Program, Boston, MA 02115 USA. [Peteet, John R.] Harvard Univ, Sch Med, Boston, MA USA. [Peteet, John R.; Balboni, Michael J.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Peteet, JR (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 44 Binney St, Boston, MA 02115 USA. EM jpeteet@partners.org NR 135 TC 38 Z9 40 U1 1 U2 60 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JUL PY 2013 VL 63 IS 4 BP 280 EP 289 DI 10.3322/caac.21187 PG 10 WC Oncology SC Oncology GA 174YA UT WOS:000321192700006 PM 23625473 ER PT J AU Ly, A AF Ly, Amy TI Talking to patients about a diagnosis of malignancy in a fine-needle aspiration clinic setting SO CANCER CYTOPATHOLOGY LA English DT Editorial Material C1 [Ly, Amy] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ly, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ly, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUL PY 2013 VL 121 IS 7 BP 339 EP 340 DI 10.1002/cncy.21315 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 181VT UT WOS:000321698500001 PM 23853169 ER PT J AU Faquin, WC AF Faquin, William C. TI Reply to can a gene-expression classifier with high negative predictive value solve the indeterminate thyroid fine-needle aspiration dilemma? SO CANCER CYTOPATHOLOGY LA English DT Letter ID CYTOLOGY C1 Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Faquin, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 3 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUL PY 2013 VL 121 IS 7 BP 404 EP 404 DI 10.1002/cncy.21305 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 181VT UT WOS:000321698500012 PM 23765728 ER PT J AU Lui, VWY Hedberg, ML Li, H Vangara, BS Pendleton, K Zeng, Y Lu, YL Zhang, QH Du, Y Gilbert, BR Freilino, M Sauerwein, S Peyser, ND Xiao, D Diergaarde, B Wang, L Chiosea, S Seethala, R Johnson, JT Kim, S Duvvuri, U Ferris, RL Romkes, M Nukui, T Ng, PKS Garraway, LA Hammerman, PS Mills, GB Grandis, JR AF Lui, Vivian W. Y. Hedberg, Matthew L. Li, Hua Vangara, Bhavana S. Pendleton, Kelsey Zeng, Yan Lu, Yiling Zhang, Qiuhong Du, Yu Gilbert, Breean R. Freilino, Maria Sauerwein, Sam Peyser, Noah D. Xiao, Dong Diergaarde, Brenda Wang, Lin Chiosea, Simion Seethala, Raja Johnson, Jonas T. Kim, Seungwon Duvvuri, Umamaheswar Ferris, Robert L. Romkes, Marjorie Nukui, Tomoko Patrick Kwok-Shing Ng Garraway, Levi A. Hammerman, Peter S. Mills, Gordon B. Grandis, Jennifer R. TI Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers SO CANCER DISCOVERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-RECEPTOR; ENDOMETRIAL CANCER; PIK3CA MUTATION; GENE; PTEN; ACTIVATION; PATTERNS; REVEALS; BREAST AB Genomic findings underscore the heterogeneity of head and neck squamous cell carcinoma (HNSCC). Identification of mutations that predict therapeutic response would be a major advance. We determined the mutationally altered, targetable mitogenic pathways in a large HNSCC cohort. Analysis of whole-exome sequencing data from 151 tumors revealed the phosphoinositide 3-kinase (PI3K) pathway to be the most frequently mutated oncogenic pathway (30.5%). PI3K pathway-mutated HNSCC tumors harbored a significantly higher rate of mutations in known cancer genes. In a subset of human papillomavirus-positive tumors, PIK3CA or PIK3R1 was the only mutated cancer gene. Strikingly, all tumors with concurrent mutation of multiple PI3K pathway genes were advanced (stage IV), implicating concerted PI3K pathway aberrations in HNSCC progression. Patient-derived tumorgrafts with canonical and noncanonical PIK3CA mutations were sensitive to an mTOR/PI3K inhibitor (BEZ-235), in contrast to PIK3CA-wild-type tumorgrafts. These results suggest that PI3K pathway mutations may serve as predictive biomarkers for treatment selection. SIGNIFICANCE: Treatment options for HNSCC are limited, in part, because of an incomplete understanding of the targetable mutations that "drive" tumor growth. Here, we define a subgroup of HNSCC harboring activating mutations of genes in the PI3K pathway where targeting the pathway shows antitumor efficacy. These results suggest that PI3K pathway mutation assessment may be used to guide HNSCC therapy. (C) 2013 AACR. C1 [Lui, Vivian W. Y.; Hedberg, Matthew L.; Li, Hua; Vangara, Bhavana S.; Pendleton, Kelsey; Zeng, Yan; Zhang, Qiuhong; Du, Yu; Gilbert, Breean R.; Freilino, Maria; Sauerwein, Sam; Peyser, Noah D.; Xiao, Dong; Johnson, Jonas T.; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L.; Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Hedberg, Matthew L.; Grandis, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. [Wang, Lin; Chiosea, Simion; Seethala, Raja] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Romkes, Marjorie; Nukui, Tomoko] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Diergaarde, Brenda] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Lu, Yiling; Patrick Kwok-Shing Ng; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Garraway, Levi A.; Hammerman, Peter S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Sch Med, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu RI Li, Hua/C-3126-2013; LI, HUA/I-9569-2014; Lui, Vivian/I-5458-2016; OI Diergaarde, Brenda/0000-0002-3578-6547; Ferris, Robert/0000-0001-6605-2071 FU American Cancer Society; Patricia L. Knebel Fund of the Pittsburgh Foundation; National Cancer Institute [K08 1K08CA163677]; University of Pittsburgh Cancer Institute Cancer Center Support Grant [P30CA047904ALL]; [P50 CA097190]; [5T32DC000066-10] FX The study is supported by P50 CA097190 and the American Cancer Society (to J.R. Grandis), the Patricia L. Knebel Fund of the Pittsburgh Foundation (to V.W.Y. Lui), National Cancer Institute K08 1K08CA163677 (to P.S. Hammerman), University of Pittsburgh Cancer Institute Cancer Center Support Grant P30CA047904ALL (to M. Romkes and T. Nukui), and funding support for MLH (5T32DC000066-10 to J.R. Grandis, Research Training in Otolaryngology, University of Pittsburgh). NR 28 TC 160 Z9 162 U1 2 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JUL PY 2013 VL 3 IS 7 BP 761 EP 769 DI 10.1158/2159-8290.CD-13-0103 PG 9 WC Oncology SC Oncology GA 180SE UT WOS:000321615600024 PM 23619167 ER PT J AU Zhang, YQ Shin, SJ Liu, D Ivanova, E Foerster, F Ying, HQ Zheng, HW Xiao, Y Chen, Z Protopopov, A DePinho, RA Paik, JH AF Zhang, Yuqing Shin, Sandra J. Liu, Debra Ivanova, Elena Foerster, Friedrich Ying, Haoqiang Zheng, Hongwu Xiao, Yonghong Chen, Zhengming Protopopov, Alexei DePinho, Ronald A. Paik, Ji-Hye TI ZNF365 Promotes Stability of Fragile Sites and Telomeres SO CANCER DISCOVERY LA English DT Article ID BREAST-CANCER RISK; HUMAN-CELLS; HOMOLOGOUS RECOMBINATION; MAMMALIAN TELOMERES; GENOME INSTABILITY; COMMON VARIANTS; DNA-PKCS; DYSFUNCTION; MAINTENANCE; PATHWAY AB Critically short telomeres activate cellular senescence or apoptosis, as mediated by the tumor suppressor p53, but in the absence of this checkpoint response, telomere dysfunction engenders chromosomal aberrations and cancer. Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability. Germline polymorphisms in the ZNF365 locus are associated with increased cancer risk, including those associated with telomere dysfunction. On the mechanistic level, ZNF365 suppresses expression of a subset of common fragile sites, including telomeres. In the absence of ZNF365, defective telomeres engage in aberrant recombination of telomere ends, leading to increased telomere sister chromatid exchange and formation of anaphase DNA bridges, including ultra-fine DNA bridges, and ultimately increased cytokinesis failure and aneuploidy. Thus, the p53-ZNF365 axis contributes to genomic stability in the setting of telomere dysfunction. SIGNIFICANCE: The contribution of the p53-ZNF365-telomere axis in the suppression of genomic instability illuminates how alterations in this pathway may confer increased cancer risk for individuals harboring germline alterations in the ZNF365 locus. (C) 2013 AACR. C1 [Zhang, Yuqing; Shin, Sandra J.; Liu, Debra; Paik, Ji-Hye] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Chen, Zhengming] Weill Cornell Med Coll, Dept Publ Hlth, Div Biostat & Epidemiol, New York, NY 10065 USA. [Zheng, Hongwu] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Ivanova, Elena; Foerster, Friedrich; Xiao, Yonghong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ying, Haoqiang; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Protopopov, Alexei; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77030 USA. RP Paik, JH (reprint author), Weill Cornell Med Coll, 1300 York Ave C-336, New York, NY 10065 USA. EM rdepinho@mdanderson.org; jep2025@med.cornell.edu OI Zheng, Hongwu/0000-0002-5823-4913 FU NIH National Cancer Institute [R01CA84628, U01CA141508]; Belfer Foundation; American Cancer Society Research Professorship; Weill Cornell Medical College; Ellison Medical Foundation [AG-NS-0646-10]; Sidney Kimmel Foundation [SKF-092] FX This work is supported by grants from the NIH National Cancer Institute (R01CA84628, U01CA141508) and the Belfer Foundation, and an American Cancer Society Research Professorship (to R.A. DePinho). J.-H. Paik is supported by the Weill Cornell Medical College, the Ellison Medical Foundation (AG-NS-0646-10), and the Sidney Kimmel Foundation (SKF-092). NR 49 TC 4 Z9 4 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JUL PY 2013 VL 3 IS 7 BP 798 EP 811 DI 10.1158/2159-8290.CD-12-0536 PG 14 WC Oncology SC Oncology GA 180SE UT WOS:000321615600027 PM 23776040 ER PT J AU Tercyak, KP Mays, D DeMarco, TA Peshkin, BN Valdimarsdottir, HB Schneider, KA Garber, JE Patenaude, AF AF Tercyak, Kenneth P. Mays, Darren DeMarco, Tiffani A. Peshkin, Beth N. Valdimarsdottir, Heiddis B. Schneider, Katherine A. Garber, Judy E. Patenaude, Andrea Farkas TI Decisional Outcomes of Maternal Disclosure of BRCA1/2 Genetic Test Results to Children SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLICY STATEMENT UPDATE; CANCER SUSCEPTIBILITY; PARENTS ATTITUDES; AMERICAN-SOCIETY; BREAST-CANCER; DISEASE RISK; COMMUNICATION; FAMILY; INFORMATION; MOTHERS AB Background: Although BRCA1/2 genetic testing is discouraged in minors, mothers may disclose their own results to their children. Factors affecting patients' disclosure decisions and patient outcomes of disclosure are largely unknown. Methods: Mothers (N = 221) of children aged 8 to 21 years enrolled in this prospective study of family communication about cancer genetic testing. Patients underwent BRCA1/2 genetic counseling and testing, and completed standardized behavioral assessments before and 1-month following receipt of their results. Results: Most patients (62.4%) disclosed BRCA1/2 test results to their child. Patients were more likely to disclose if they received negative or uninformative versus positive results [OR = 3.11; 95% confidence interval (CI), 1.11-8.71; P = .03], their child was 13 years of age or more versus younger (OR = 5.43; 95% CI, 2.18-13.53; P < .001), and as the ratio of patients' perceived benefits of disclosure outweighed potential risks (OR - 2.40; 95% CI, 1.63-3.54; P < .001). Postdecision satisfaction about disclosure was lowest among nondisclosing patients (P < .001) and those reporting greater decisional conflict (P < .001). Conclusions: Patients commonly discuss their BRCA1/2 results with their teenage and young adult children, especially if the information is perceived as beneficial. Satisfaction with disclosure decision making remains lowest among nondisclosing and conflicted patients. Family communication decision support adjuncts to genetic counseling are needed to help ameliorate these effects. Impact: This study describes the prevalence of family communication about maternal BRCA1/2 genetic testing with minor children, and decisions and outcomes of disclosure. (c) 2013 AACR. C1 [Tercyak, Kenneth P.; Mays, Darren; DeMarco, Tiffani A.; Peshkin, Beth N.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Valdimarsdottir, Heiddis B.] Mt Sinai Sch Med, New York, NY USA. [Schneider, Katherine A.; Garber, Judy E.; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tercyak, KP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, 3300 Whitehaven St, Washington, DC 20007 USA. EM tercyakk@georgetown.edu FU Public Health Service Grant National Human Genome Research Institute [R01HG002686]; Biostatistics and Bioinformatics Shared Resource of Georgetown Lombardi Comprehensive Cancer Center through Comprehensive Cancer Center [P30CA051008] FX This work was supported in part by Public Health Service Grant R01HG002686 from the National Human Genome Research Institute and, the Biostatistics and Bioinformatics Shared Resource of Georgetown Lombardi Comprehensive Cancer Center through Comprehensive Cancer Center Support Grant P30CA051008. NR 33 TC 5 Z9 5 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2013 VL 22 IS 7 BP 1260 EP 1266 DI 10.1158/1055-9965.EPI-13-0198 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 176SC UT WOS:000321323600008 PM 23825307 ER PT J AU Stylianopoulos, T Martin, JD Snuderl, M Mpekris, F Jain, SR Jain, RK AF Stylianopoulos, Triantafyllos Martin, John D. Snuderl, Matija Mpekris, Fotios Jain, Saloni R. Jain, Rakesh K. TI Coevolution of Solid Stress and Interstitial Fluid Pressure in Tumors During Progression: Implications for Vascular Collapse SO CANCER RESEARCH LA English DT Article ID CANCER-CELLS; ANTIANGIOGENIC THERAPY; MATHEMATICAL-MODEL; GROWING TUMOR; GROWTH; MACROMOLECULES; NORMALIZATION; HYPERTENSION; TRANSPORT; BLOOD AB The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently showed that growth-induced solid stress is on the order of 1.3 to 13.0 kPa (10-100 mmHg) - high enough to cause compression of fragile blood vessels, resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress, and fluid pressure. First, we conducted in vivo experiments and found that growth-induced stress is related to tumor volume through a biexponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared with the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histologic sections of human cancers that show such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels. (C) 2013 AACR. C1 [Stylianopoulos, Triantafyllos; Mpekris, Fotios] Univ Cyprus, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. [Martin, John D.; Jain, Saloni R.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Snuderl, Matija] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Martin, John D.; Snuderl, Matija; Jain, Saloni R.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Martin, John D.; Snuderl, Matija; Jain, Saloni R.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Snuderl, Matija] NYU, Dept Pathol, Langone Med Ctr, New York, NY 10016 USA. [Snuderl, Matija] Sch Med, New York, NY USA. RP Stylianopoulos, T (reprint author), Univ Cyprus, Kallipoleos 75, CY-1678 Nicosia, Cyprus. EM tstylian@ucy.ac.cy; jain@steele.mgh.harvard.edu RI Martin, John/L-6892-2016; OI Martin, John/0000-0002-9828-8203; Stylianopoulos, Triantafyllos/0000-0002-3093-1696; Snuderl, Matija/0000-0003-0752-0917 FU European Commission [PIRG08-GA-2010-276894]; Paul Calabresi Career Development Award in Clinical Oncology [2K12CA090354-11]; National Cancer Institute [P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, R01-CA098706]; DoD Breast Cancer Research Innovator award [W81XWH-10-1-0016] FX This study was financially supported by the European Commission Marie-Curie (grant no. PIRG08-GA-2010-276894; to T. Stylianopoulos), Paul Calabresi Career Development Award in Clinical Oncology (2K12CA090354-11; to M. Snuderl), the National Cancer Institute (P01-CA080124, R01-CA126642, R01-CA115767, R01-CA096915, R01-CA085140, R01-CA098706, and Federal Share Income Grant), and a DoD Breast Cancer Research Innovator award (W81XWH-10-1-0016; to R.K. Jain). NR 32 TC 55 Z9 55 U1 0 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2013 VL 73 IS 13 BP 3833 EP 3841 DI 10.1158/0008-5472.CAN-12-4521 PG 9 WC Oncology SC Oncology GA 173WM UT WOS:000321112700004 PM 23633490 ER PT J AU Young, CD Pfefferle, AD Owens, P Kuba, MG Rexer, BN Balko, JM Sanchez, V Cheng, HL Perou, CM Zhao, JJ Cook, RS Arteaga, CL AF Young, Christian D. Pfefferle, Adam D. Owens, Philip Kuba, Maria G. Rexer, Brent N. Balko, Justin M. Sanchez, Violeta Cheng, Hailing Perou, Charles M. Zhao, Jean J. Cook, Rebecca S. Arteaga, Carlos L. TI Conditional Loss of ErbB3 Delays Mammary Gland Hyperplasia Induced by Mutant PIK3CA without Affecting Mammary Tumor Latency, Gene Expression, or Signaling SO CANCER RESEARCH LA English DT Article ID HUMAN BREAST-TUMORS; PHOSPHATIDYLINOSITOL 3-KINASE; PI3K PATHWAY; PHOSPHOINOSITIDE 3-KINASE; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; TYROSINE KINASE; UP-REGULATION; CANCER; MUTATIONS AB Mutations in PIK3CA, the gene encoding the p110 alpha catalytic subunit of phosphoinositide 3-kinase (PI3K), have been shown to transform mammary epithelial cells (MEC). Studies suggest this transforming activity requires binding of mutant p110a via p85 to phosphorylated YXXM motifs in activated receptor tyrosine kinases (RTK) or adaptors. Using transgenic mice, we examined if ErbB3, a potent activator of PI3K, is required for mutant PIK3CA-mediated transformation of MECs. Conditional loss of ErbB3 in mammary epithelium resulted in a delay of PIK3CA(H1047R)-dependent mammary gland hyperplasia, but tumor latency, gene expression, and PI3K signaling were unaffected. In ErbB3-deficient tumors, mutant PI3K remained associated with several tyrosyl phosphoproteins, potentially explaining the dispensability of ErbB3 for tumorigenicity and PI3K activity. Similarly, inhibition of ErbB RTKs with lapatinib did not affect PI3K signaling in PIK3CA(H1047R)-expressing tumors. However, the p110a-specific inhibitor BYL719 in combination with lapatinib impaired mammary tumor growth and PI3K signaling more potently than BYL719 alone. Furthermore, coinhibition of p110a and ErbB3 potently suppressed proliferation and PI3K signaling in human breast cancer cells harboring PIK3CA(H1047R). These data suggest that PIK3CA(H1047R)-driven tumor growth and PI3K signaling can occur independently of ErbB RTKs. However, simultaneous blockade of p110 alpha and ErbB RTKs results in superior inhibition of PI3K and mammary tumor growth, suggesting a rational therapeutic combination against breast cancers harboring PIK3CA activating mutations. C1 [Young, Christian D.; Rexer, Brent N.; Balko, Justin M.; Sanchez, Violeta; Arteaga, Carlos L.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Owens, Philip; Cook, Rebecca S.; Arteaga, Carlos L.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. [Kuba, Maria G.] Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA. [Rexer, Brent N.; Cook, Rebecca S.; Arteaga, Carlos L.] Vanderbilt Ingram Canc Ctr, Breast Canc Res Program, Nashville, TN USA. [Pfefferle, Adam D.; Perou, Charles M.] Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. [Pfefferle, Adam D.; Perou, Charles M.] Univ N Carolina, Dept Lab Med, Chapel Hill, NC USA. [Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Pfefferle, Adam D.; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Cheng, Hailing; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Arteaga, CL (reprint author), Vanderbilt Univ, Med Ctr, Div Hematol Oncol, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu OI Owens, Philip/0000-0002-1452-9285; Perou, Charles/0000-0001-9827-2247 FU American Cancer Society Clinical Research Professorship Grant [CRP-07-234]; Breast Cancer Specialized Program of Research Excellence (SPORE) [P50 CA98131]; Vanderbilt-Ingram Cancer Center Support Grant [P30 CA68485]; Entertainment Industry Foundation [SU2C-AACR-DT0209]; Susan G. Komen for the Cure grant [KG100677, SAC100013, PDF12229712]; Department of Defense postdoctoral fellowship grant [W81XWH-12-1-0026]; [CA80195]; [CA143126] FX This work was supported by R01 grants CA80195 (C.L. Arteaga) and CA143126 (R.S. Cook), American Cancer Society Clinical Research Professorship Grant CRP-07-234 (C.L. Arteaga), Breast Cancer Specialized Program of Research Excellence (SPORE) P50 CA98131, Vanderbilt-Ingram Cancer Center Support Grant P30 CA68485, a Stand Up to Cancer Dream Team Translational Research Grant from the Entertainment Industry Foundation (SU2C-AACR-DT0209), and Susan G. Komen for the Cure grants KG100677 (R.S. Cook), SAC100013 (C.L. Arteaga) and PDF12229712 (J.M. Balko). C.D. Young is supported by Department of Defense postdoctoral fellowship grant W81XWH-12-1-0026. NR 45 TC 12 Z9 12 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2013 VL 73 IS 13 BP 4075 EP 4085 DI 10.1158/0008-5472.CAN-12-4579 PG 11 WC Oncology SC Oncology GA 173WM UT WOS:000321112700025 PM 23633485 ER PT J AU Yeh, RW Drachman, DE AF Yeh, Robert W. Drachman, Douglas E. TI Coronary Chronic Total Occlusion in the Elderly SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID SURGERY C1 [Yeh, Robert W.; Drachman, Douglas E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Yeh, RW (reprint author), GRB800 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM ryeh@partners.org NR 5 TC 0 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL 1 PY 2013 VL 82 IS 1 BP 93 EP 94 DI 10.1002/ccd.25013 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 169NN UT WOS:000320787100022 PM 23788388 ER PT J AU Kern, M Applegate, R Bach, RG Bailey, SR Bashore, TM Bass, TA Bell, M de Bruyne, B Garratt, N Jeremias, A Kereiakes, DJ Klein, LW Krucoff, MW Mintz, GS Morrison, D Ohman, EM Pichard, A Rosenfield, K Samady, H Stone, GW Tommaso, C Turi, ZG Uretsky, B Vetrovec, G Weiner, BH Welt, F Yeung, AC AF Kern, Morton Applegate, Robert Bach, Richard G. Bailey, Steven R. Bashore, Thomas M. Bass, Theodore A. Bell, Malcolm de Bruyne, Bernard Garratt, N. Jeremias, Allen Kereiakes, Dean J. Klein, Lloyd W. Krucoff, Mitchell W. Mintz, Gary S. Morrison, Douglas Ohman, E. Magnus Pichard, Augusto Rosenfield, Kenneth Samady, Habib Stone, Gregg W. Tommaso, Carl Turi, Zoltan G. Uretsky, Barry Vetrovec, George Weiner, Bonnie H. Welt, Frederick Yeung, Alan C. TI Conversation in cardiology: Should FFR and IVUS be counted as PCI? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 [Kern, Morton] Univ Calif Irvine, Irvine, CA 92717 USA. [Applegate, Robert] Wake Forest Sch Med, Winston Salem, NC USA. [Bach, Richard G.] Washington Univ, Sch Med, St Louis, MO USA. [Bailey, Steven R.] Univ Texas Hlth Sci San Antonio, San Antonio, TX USA. [Bashore, Thomas M.; Krucoff, Mitchell W.; Ohman, E. Magnus] Duke Univ, Med Ctr, Durham, NC USA. [Bass, Theodore A.] Univ Florida, Jacksonville, FL USA. [Bell, Malcolm] Mayo Clin, Rochester, MN USA. [de Bruyne, Bernard] Intervent Cardiol, Aalst, Belgium. [Garratt, N.] Lenox Hill Heart & Vasc Inst New York, New York, NY USA. [Jeremias, Allen] SUNY Stony Brook, Med Ctr, New York, NY USA. [Kereiakes, Dean J.] Ohio State Univ, Columbus, OH 43210 USA. [Klein, Lloyd W.] Rush Med Coll, Chicago, IL 60612 USA. [Mintz, Gary S.] Cardiovasc Res Fdn, New York, NY USA. [Morrison, Douglas] Yakima Heart Ctr, Yakima, WA USA. [Pichard, Augusto] Washington Heart Ctr, Washington, DC USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Samady, Habib] Emory Univ, Sch Med, Atlanta, GA USA. [Stone, Gregg W.] Columbia Univ, Columbia Presbyterian Med Ctr, Med Ctr, New York, NY 10032 USA. [Tommaso, Carl] Rush Univ, Sch Med, Chicago, IL 60612 USA. [Turi, Zoltan G.] Cooper Univ Hosp, Camden, NJ USA. [Uretsky, Barry] Univ Arkansas, Little Rock, AR 72204 USA. [Vetrovec, George] Univ Virginia, Richmond, VA USA. [Weiner, Bonnie H.] Univ Massachusetts, Worcester, MA USA. [Welt, Frederick] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeung, Alan C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Kern, M (reprint author), Univ Calif Irvine, Irvine, CA 92717 USA. EM mkern@uci.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUL 1 PY 2013 VL 82 IS 1 BP 110 EP 115 DI 10.1002/ccd.24854 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 169NN UT WOS:000320787100025 PM 23404738 ER PT J AU Bergese, SD Minkowitz, HS Arpino, PA Sane, DC Levy, JH AF Bergese, Sergio D. Minkowitz, Harold S. Arpino, Paul A. Sane, David C. Levy, Jerrold H. TI Multicenter Trial of Desirudin for the Prophylaxis of Thrombosis: An Alternative to Heparin-Based Anticoagulation (DESIR-ABLE) SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE bleeding; anticoagulants; deep venous thrombosis; thrombocytopenia; venous thromboembolism ID FACTOR 4/HEPARIN ANTIBODIES; TOTAL HIP-REPLACEMENT; INDUCED THROMBOCYTOPENIA; VENOUS THROMBOEMBOLISM; RECOMBINANT HIRUDIN; PREVENTION; COMPLICATIONS; MANAGEMENT; EFFICACY; THERAPY AB Desirudin, a subcutaneously (SC) administered direct thrombin inhibitor, is indicated for prevention of venous thromboembolic events (VTEs) after total joint replacement surgery. DESIR-ABLE (multicenter trial of desirudin for the prophylaxis of thrombosis: an alternative to heparin-based anticoagulation) was a multicenter, open-label, single-arm study of hospitalized patients requiring VTE protection designed to extend the safety profile for desirudin to include a broad population of perioperative/critically ill patients. The primary end point was major bleeding. A total of 516 patients undergoing major surgery (378, 73%) or who were medically ill with prolonged immobility (138, 27%) were enrolled at 19 centers and received desirudin 15 mg Q12H. Many patients had high-risk features for bleeding and thrombosis such as thrombocytopenia (<100x10(9)/mL, n = 50), severe obesity (body mass index >35, n = 145), and renal impairment (creatinine clearance <60 mL/min, n = 292). There were no major bleeds and no VTE-related deaths in this study. The DESIR-ABLE demonstrated the safety of desirudin in critically ill perioperative and medical patients. Trials in specific surgical or medically ill patients are needed to confirm these findings. C1 [Bergese, Sergio D.] Ohio State Univ, Columbus, OH 43210 USA. [Minkowitz, Harold S.] Mem Hermann Mem City Med Ctr, Houston, TX USA. [Arpino, Paul A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sane, David C.] Virginia Tech Caril Sch Med & Res Ctr, Roanoke, VA USA. [Levy, Jerrold H.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Levy, JH (reprint author), Emory Univ, Sch Med, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM jlevy01@emory.edu NR 21 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD JUL PY 2013 VL 19 IS 4 BP 418 EP 423 DI 10.1177/1076029612452779 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 176ME UT WOS:000321308000010 PM 22802554 ER PT J AU Nigwekar, SU Brunelli, SM Meade, D Wang, WL Hymes, J Lacson, E AF Nigwekar, Sagar U. Brunelli, Steven M. Meade, Debra Wang, Weiling Hymes, Jeffrey Lacson, Eduardo, Jr. TI Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENT; RISK-FACTORS; CALCIPHYLAXIS; STRATEGIES; CINACALCET; ULCER; LEG AB Background and objective Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration in CUA, but no studies have systematically evaluated this treatment. Design, setting, participants, & measurements This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters. Results Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy. Conclusions Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study. C1 [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Nigwekar, Sagar U.] Harvard Univ, Sch Med, Scholars Clin Sci Program, Boston, MA USA. [Brunelli, Steven M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Brunelli, Steven M.] DaVita Clin Res, Minneapolis, MN USA. [Meade, Debra; Wang, Weiling; Hymes, Jeffrey; Lacson, Eduardo, Jr.] Fresenius Med Care North Amer, Waltham, MA USA. RP Nigwekar, SU (reprint author), Massachusetts Gen Hosp, Bulfinch 127, Boston, MA 02114 USA. EM sagarnigs@gmail.com FU Clinical Scientist in Nephrology award from the American Kidney Fund FX S.N. is supported by the Clinical Scientist in Nephrology award from the American Kidney Fund. NR 38 TC 42 Z9 47 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2013 VL 8 IS 7 BP 1162 EP 1170 DI 10.2215/CJN.09880912 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 178DA UT WOS:000321423100015 PM 23520041 ER PT J AU Thomas, BA Rodriguez, RA Boyko, EJ Robinson-Cohen, C Fitzpatrick, AL O'Hare, AM AF Thomas, Bernadette A. Rodriguez, Rudolph A. Boyko, Edward J. Robinson-Cohen, Cassianne Fitzpatrick, Annette L. O'Hare, Ann M. TI Geographic Variation in Black-White Differences in End-of-Life Care for Patients with ESRD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; RACIAL-DIFFERENCES; AFRICAN-AMERICAN; UNITED-STATES; NEIGHBORHOOD POVERTY; TREATMENT INTENSITY; REGIONAL-VARIATIONS; ETHNIC DISPARITIES; ELDERLY-PATIENTS; NEPHROLOGY CARE AB Background and objectives Patterns of end-of-life care among patients with ESRD differ by race. Whether the magnitude of racial differences in end-of-life care varies across regions is not known. Design, setting, participants, & measurements This observational cohort study used data from the US Renal Data System and regional health care spending patterns from the Dartmouth Atlas of Healthcare. The cohort included 101,331 black and white patients 18 years and older who initiated chronic dialysis or received a kidney transplant between June 1, 2005, and September 31, 2008, and died before October 1, 2009. Black white differences in the odds of in-hospital death, dialysis discontinuation, and hospice referral by quintile of end-of-life expenditure index (EOL-EI) were examined. Results In adjusted analyses, the odds ratios for dialysis discontinuation for black versus white patients ranged from 0.47 (95% confidence interval=0.43 to 0.51) in the highest quintile of EOL-EI to 0.63 (95% confidence interval=0.54 to 0.74) in the lowest quintile (P for interaction<0.001). Hospice referral ranged from 0.55 (95% confidence interval:=0.50 to 0.60) in the highest quintile of EOL-EI to 0.82(95% confidence interval=0.69 to 0.96) in the lowest quintile (P for interaction<0.001). The association of race with in-hospital death also differed in magnitude across quintiles of EOL-EI, ranging from 1.21 (95% confidence interval=1.08 to 1.35) in the highest quintile of EOL-EI to 1.47 (95% confidence interval=1.27 to 1.71) in the second quintile (P for interaction<0.001). Conclusions There are pronounced black white differences in patterns of hospice referral and dialysis discontinuation among patients with ESRD that vary substantially across regions of the United States. C1 [Thomas, Bernadette A.; Rodriguez, Rudolph A.; O'Hare, Ann M.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Boyko, Edward J.; Robinson-Cohen, Cassianne; Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rodriguez, Rudolph A.; O'Hare, Ann M.] Vet Affairs Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Thomas, BA (reprint author), Univ Washington, 1959 NE Pacific St,Box 356521, Seattle, WA 98195 USA. EM bthomas19@gmail.com OI Robinson-Cohen, Cassianne/0000-0003-4783-7046 FU Ruth L. Kirschstein National Research Service Award from the National Institutes of Health [F32 DK093167-01]; Beeson Career Development Award from the National Institute on Aging [K 1K23AG28980] FX We acknowledge the following grant support: Ruth L. Kirschstein National Research Service Award F32 DK093167-01 from the National Institutes of Health (to B.A.T.) and Beeson Career Development Award K 1K23AG28980 from the National Institute on Aging (to A.M.O.). NR 50 TC 11 Z9 11 U1 2 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2013 VL 8 IS 7 BP 1171 EP 1178 DI 10.2215/CJN.06780712 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 178DA UT WOS:000321423100016 PM 23580783 ER PT J AU Palomino, HL Rifkin, DE Anderson, C Criqui, MH Whooley, MA Ix, JH AF Palomino, Heather L. Rifkin, Dena E. Anderson, Cheryl Criqui, Michael H. Whooley, Mary A. Ix, Joachim H. TI 24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; CHRONIC KIDNEY-DISEASE; 3RD NATIONAL-HEALTH; SERUM PHOSPHORUS; DIETARY PHOSPHORUS; MINERAL METABOLISM; RENAL-DISEASE; CALCIUM; CKD AB Background and objectives Higher morning serum phosphorus has been associated with cardiovascular disease (CVD) in patients with or without CKD. In patients with CKD and a phosphorous level >4.6 mg/dl, the Kidney Disease Improving Global Outcomes guidelines recommend dietary phosphorus restriction. However, whether phosphorus restriction influences serum phosphorus concentrations and whether dietary phosphorus is itself associated with CVD or death are uncertain. Design, setting, participants, & measurements Among 880 patients with stable CVD and normal kidney function to moderate CKD, 24-hour urine phosphorus excretion (UPE) and serum phosphorus were measured at baseline. Participants were followed for a median. of 7.4 years for CVD events and all-cause mortality. Results Mean +/- SD age was 67 +/- 11 years, estimated GFR (eGFR) was 71 +/- 22 ml/min per 1.73 m(2), and serum phosphorus was 3.7 +/- 0.6 mg/dl. Median UPE was 632 (interquartile range, 439, 853) mg/d. In models adjusted for demographic characteristics and eGFR, UPE was weakly and nonsignificantly associated with serum phosphorus (0.03 mg/dl higher phosphorus per 300 mg higher UPE; P=0.07). When adjusted for demographics, eGFR, and CVD risk factors, each 300-mg higher UPE was associated with 17% lower risk of CVD events. The association of UPE with all-cause mortality was not statistically significant (hazard ratio, 0.93; 95% confidence interval, 0.82 to 1.05). Results were similar irrespective of CKD status (P interactions > 0.87). Conclusions Among outpatients with stable CVD, the magnitude of the association of UPE with morning serum phosphorus is modest. Greater UPE is associated with lower risk for CVD events. The association was similar for all-cause mortality but was not statistically significant. C1 [Palomino, Heather L.; Rifkin, Dena E.; Anderson, Cheryl; Criqui, Michael H.; Ix, Joachim H.] Univ Calif San Diego, Sch Med, San Diego, CA 92161 USA. [Rifkin, Dena E.; Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Rifkin, Dena E.; Anderson, Cheryl; Criqui, Michael H.; Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Whooley, Mary A.] Univ Calif San Diego, Dept Epidemiol & Biostat, San Diego, CA 92161 USA. [Rifkin, Dena E.; Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 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 FU National Heart, Lung, and Blood Institute [1R01HL096851, R01 HL079235]; American Heart Association Fellow-to-Faculty Transition Award; Sandra Daugherty Foundation; National Institutes of Health [TL1TR00098]; Department of Veterans Affairs; American Federation of Aging Research; Robert Wood Johnson Foundation; Nancy Kirwan Heart Research Fund; Ischemia Research and Education Foundation FX This study was supported by grants from the National Heart, Lung, and Blood Institute (1R01HL096851) (J.H.I.), an American Heart Association Fellow-to-Faculty Transition Award (J.H.I.), and an award from the Sandra Daugherty Foundation (J.H.I.). Heather Palomino was supported by a training grant from the National Institutes of Health (TL1TR00098). The Heart and Soul Study was funded by the Department of Veterans Affairs, American Federation of Aging Research, Robert Wood Johnson Foundation, Nancy Kirwan Heart Research Fund, Ischemia Research and Education Foundation, and the National Heart, Lung, and Blood Institute (R01 HL079235). NR 32 TC 11 Z9 11 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL PY 2013 VL 8 IS 7 BP 1202 EP 1210 DI 10.2215/CJN.11181012 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 178DA UT WOS:000321423100020 PM 23539231 ER PT J AU Price, M Gros, DF Strachan, M Ruggiero, KJ Acierno, R AF Price, Matthew Gros, Daniel F. Strachan, Martha Ruggiero, Kenneth J. Acierno, Ron TI Combat Experiences, Pre-Deployment Training, and Outcome of Exposure Therapy for Post-Traumatic Stress Disorder in Operation Enduring Freedom/Operation Iraqi Freedom Veterans SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE PTSD; OEF; OIF; Veterans; Exposure Therapy; Combat Exposure; Pre-Deployment Preparedness ID COGNITIVE-BEHAVIORAL THERAPY; CHILD SEXUAL-ABUSE; ADMINISTERED PTSD SCALE; MENTAL-HEALTH; PROLONGED EXPOSURE; TRAUMATIC EVENTS; CLINICAL-TRIALS; SUBSTANCE USE; RISK-FACTORS; SYMPTOMS AB The association between exposure to multiple potentially traumatic events (PTEs) and subsequent increased risk of post-traumatic stress disorder (PTSD) is well established. However, less is known about the relation between exposure to numerous PTEs, as is typical with military service, and treatment outcome. Furthermore, there has been little research examining military specific protective factors, such as pre-deployment preparedness, on PTSD treatment response. The current study investigated combat exposure and potential moderators of treatment outcome for exposure therapy in Operation Enduring Freedom/ Operation Iraqi Freedom (OEF/OIF) veterans with PTSD. One hundred and eleven OEF/OIF veterans diagnosed with PTSD participated in 8weeks of exposure therapy. Results indicated that increased combat exposure was associated with a reduced rate of change in PTSD symptoms but not depression symptoms. These findings were consistent across two measures of combat exposure. There was preliminary support for the moderating effect of pre-deployment preparedness on the association between combat exposure and treatment response. Together, these findings suggest that increased combat exposure is associated with poor treatment response in veterans with PTSD; however, this can be reduced by elevated pre-deployment preparedness. Copyright (C) 2012 John Wiley & Sons, Ltd. Key Practitioner Message: Increased combat exposure is associated with poorer treatment response. Pre-deployment training is associated with improved treatment response. PTSD interventions should account for the frequency of combat in military personnel. C1 [Price, Matthew; Gros, Daniel F.; Strachan, Martha; Ruggiero, Kenneth J.; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Price, Matthew; Gros, Daniel F.; Strachan, Martha; Ruggiero, Kenneth J.; Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. RP Price, M (reprint author), Med Univ S Carolina, Natl Crime Victims Ctr, 67 President St,MSC 861,2nd Floor IOP S, Charleston, SC 29425 USA. EM prima@musc.edu FU NIDA NIH HHS [R01 DA030143] NR 61 TC 6 Z9 6 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD JUL PY 2013 VL 20 IS 4 BP 277 EP 285 DI 10.1002/cpp.1768 PG 9 WC Psychology, Clinical SC Psychology GA 178GT UT WOS:000321434700001 PM 22253233 ER PT J AU Mina, MA Picariello, A Fewkes, JL AF Mina, Mary Alice Picariello, Anthony Fewkes, Jessica L. TI Superficial Basal Cell Carcinomas of the Head and Neck SO DERMATOLOGIC SURGERY LA English DT Article ID MOHS MICROGRAPHIC SURGERY; IMIQUIMOD 5-PERCENT CREAM; HISTOPATHOLOGICAL SUBTYPE; SITE DISTRIBUTION; LOCATION; PATIENT; TUMORS; AGE AB BACKGROUND Superficial basal cell carcinomas (BCC) are often considered a non-aggressive form of skin cancer, most often found on the trunk in younger patients. OBJECTIVE To determine the characteristics of superficial BCC of the head and neck. MATERIALS AND METHODS A retrospective review of patients undergoing Mohs micrographic surgery (MMS) for the treatment of a purely superficial BCC on the head and neck region was performed. RESULTS Superficial BCC occurred more commonly in women (66.5%) than men (33.5%), most often on chronically sun-exposed skin such as the central face and nose. Women developed superficial BCC at a younger age than men (58 vs 63 years old, p = 0.02). The clinical sizes of the tumors were significantly smaller than the final Mohs defects for all locations on the head and neck, excluding ears and scalp. Recurrence rates after MMS were 3.6% despite negative histologic margins at the time of surgery. CONCLUSION Superficial BCC are a unique subtype of BCC that tend to occur in younger patients, particularly women. Mohs surgeons need to be familiar with these tumors on the head and neck given their propensity for skip-lesions, higher recurrence rates, and significantly larger defect sizes than would be expected clinically. C1 [Mina, Mary Alice] Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. [Picariello, Anthony; Fewkes, Jessica L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Fewkes, Jessica L.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Fewkes, JL (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM JFEWKES@partners.org NR 20 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JUL PY 2013 VL 39 IS 7 BP 1003 EP 1008 DI 10.1111/dsu.12178 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 174YX UT WOS:000321195700007 PM 23465089 ER PT J AU Kim, JE Won, CH Bak, H Kositratna, G Manstein, D Dotto, GP Chang, SE AF Kim, Jeong Eun Won, Chong Hyun Bak, Hana Kositratna, Garuna Manstein, Dieter Dotto, Gian Paolo Chang, Sung Eun TI Gene Profiling Analysis of the Early Effects of Ablative Fractional Carbon Dioxide Laser Treatment on Human Skin SO DERMATOLOGIC SURGERY LA English DT Article ID PHOTODAMAGED HUMAN SKIN; HIGH-ENERGY; PROFILOMETRIC EVALUATION; COLLAGEN HOMEOSTASIS; DERMAL FIBROBLASTS; MOLECULAR ANALYSIS; YAG LASER; RESPONSES; MICRODERMABRASION; MODEL AB BACKGROUND The use of carbon dioxide (CO2) laser-mediated ablative fractional resurfacing (AFR) is currently under extensive clinical investigation, but the molecular mechanisms underlying this process are unclear. OBJECTIVES To determine the early expressed genes that are upregulated in human skin after treatment using a CO2 fractional laser. METHODS Whole human skin was irradiated using an AFR CO2 laser, and changes in gene expression after 2 and 24 hours were analyzed using microarray analysis. The results were validated using reverse transcriptase polymerase chain reaction (RT-PCR). Laser scanning confocal microscopy (LSCM) was used to investigate the expression of the validated proteins after AFR CO2 laser treatment of skin that had been biopsied from seven Korean patients. RESULTS Gene expression profiling showed that the most significantly upregulated genes in these skin samples were those encoding Wnt5a, cysteine-rich angiogenic inducer 61 (CYR61), and heat shock protein (HSP) 90. These results were confirmed using real-time RT-PCR and LSCM. CONCLUSIONS Irradiation using an AFR laser may induce the expression of Wnt5a, CYR61, and HSP90 in human skin during the early remodeling phases, suggesting that the induction of proteins may be the preceding event that is associated with the clinical effects of laser treatment. C1 [Kim, Jeong Eun; Won, Chong Hyun; Bak, Hana; Chang, Sung Eun] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Dermatol, Seoul 138736, South Korea. [Kim, Jeong Eun] Hanyang Univ, Dept Dermatol, Hanyang Univ Hosp, Coll Med, Seoul 133791, South Korea. [Kositratna, Garuna; Manstein, Dieter] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kositratna, Garuna; Manstein, Dieter] Harvard Univ, Sch Med, Boston, MA USA. [Dotto, Gian Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Chang, SE (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Dermatol, 388-1 Pungnapdong Songpagu, Seoul 138736, South Korea. EM csesnumd@gmail.com FU Institute for Asan Life Sciences [2011-415] FX S. Chang is supported by the Institute for Asan Life Sciences (2011-415). NR 44 TC 6 Z9 7 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JUL PY 2013 VL 39 IS 7 BP 1033 EP 1043 DI 10.1111/dsu.12170 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA 174YX UT WOS:000321195700011 PM 23489371 ER PT J AU Dehlinger, K Tarnowski, K House, JL Los, E Hanavan, K Bustamante, B Ahmann, AJ Ward, WK AF Dehlinger, Ky Tarnowski, Kristin House, Jody L. Los, Evan Hanavan, Kathryn Bustamante, Bryan Ahmann, Andrew J. Ward, W. Kenneth TI Can Trained Dogs Detect a Hypoglycemic Scent in Patients With Type 1 Diabetes? SO DIABETES CARE LA English DT Letter C1 [Dehlinger, Ky; Bustamante, Bryan] Portland VA Med Ctr, Vet Med Unit, Portland, OR USA. [Dehlinger, Ky] Legacy Res Inst, Dept Comparat Med, Portland, OR USA. [Los, Evan; Hanavan, Kathryn; Ward, W. Kenneth] Legacy Res Inst, Diabet Div, Portland, OR USA. [Ahmann, Andrew J.; Ward, W. Kenneth] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. [Tarnowski, Kristin; House, Jody L.] Dogs Assisting Diabet Fdn, Forest Grove, OR USA. RP Ward, WK (reprint author), Legacy Res Inst, Diabet Div, Portland, OR USA. EM kenward503@msn.com OI Los, Evan/0000-0002-7567-0178 NR 4 TC 4 Z9 4 U1 2 U2 16 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 JUL PY 2013 VL 36 IS 7 BP E98 EP + DI 10.2337/dc12-2342 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178UK UT WOS:000321472700060 PM 23801820 ER PT J AU Ananthakrishnan, AN McGinley, EL AF Ananthakrishnan, Ashwin N. McGinley, Emily L. TI Treatment of Intra-Abdominal Abscesses in Crohn's Disease: A Nationwide Analysis of Patterns and Outcomes of Care SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Percutaneous drainage; Abdominal abscess; Surgery; Bowel resection ID INFLAMMATORY-BOWEL-DISEASE; PERCUTANEOUS DRAINAGE; SURGICAL-MANAGEMENT; ULCERATIVE-COLITIS; HOSPITAL VOLUME; COLECTOMY; TERM AB Abdominal abscesses are a common complication in Crohn's disease (CD). Percutaneous drainage of such abscesses has become increasingly popular and may deliver outcomes comparable to surgical treatment; however, such comparative data are limited from single-center studies. There have been no nationally representative studies comparing different treatment modalities for abdominal abscesses. We identified all adult CD-related non-elective hospitalizations from the Nationwide Inpatient Sample 2007 that were complicated by an intra-abdominal abscess. Treatment modality was categorized into 3 strata-medical treatment alone, percutaneous drainage, and surgery. We analyzed the nationwide patterns in the treatment and outcomes of each treatment modality and examined for patient demographic, disease, or hospital-related disparities in treatment and outcome. There were an estimated 3,296 hospitalizations for abdominal abscesses in patients with CD. Approximately 39 % were treated by medical treatment alone, 29 % with percutaneous drainage, and 32 % with surgery with a significant increase in the use of percutaneous drainage since 1998 (7 %). Comorbidity burden, admission to a teaching hospital, and complicated Crohn's disease (fistulae, stricture) were associated with non-medical treatment. Use of percutaneous drainage was more common in teaching hospitals. Mean time to percutaneous drainage and surgical treatment were 4.6 and 3.3 days, respectively, and early intervention was associated with significantly shorter hospitalization. We describe the nationwide pattern in the treatment of abdominal abscesses and demonstrate an increase in the use of percutaneous drainage for the treatment of this subgroup. Early treatment intervention was predictive of shorter hospitalization. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [McGinley, Emily L.] Med Coll Wisconsin, Ctr Patient Care & Outcomes & Res, Milwaukee, WI 53226 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU American Gastroenterological Association; National Institutes of Health [K23 DK097142] FX Ananthakrishnan is supported in part by a grant from the American Gastroenterological Association and the National Institutes of Health (K23 DK097142). NR 20 TC 6 Z9 8 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2013 VL 58 IS 7 BP 2013 EP 2018 DI 10.1007/s10620-013-2579-z PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 173IA UT WOS:000321071300030 PM 23392744 ER PT J AU Mehrotra, P Jansen, K Flynn, AW Tan, TC Elmariah, S Picard, MH Hung, J AF Mehrotra, Praveen Jansen, Katrijn Flynn, Aidan W. Tan, Timothy C. Elmariah, Sammy Picard, Michael H. Hung, Judy TI Differential left ventricular remodelling and longitudinal function distinguishes low flow from normal-flow preserved ejection fraction low-gradient severe aortic stenosis SO EUROPEAN HEART JOURNAL LA English DT Article DE Aortic stenosis; Echocardiography; Remodelling; Haemodynamics ID PARADOXICAL LOW-FLOW; VALVE STENOSIS; MYOCARDIAL FIBROSIS; ECHOCARDIOGRAPHIC-ASSESSMENT; SYSTOLIC FUNCTION; SPECKLE-TRACKING; RECOMMENDATIONS; QUANTIFICATION; GUIDELINES; AFTERLOAD AB There is uncertainty in identifying patients with severe aortic stenosis (AS) with preserved left ventricular (LV) ejection fraction, low flow, and low gradients (LFLG). Prior studies propose that these patients demonstrate significant concentric remodelling and decreased survival, while others suggest that they have features and survival similar to moderate AS. We compared the clinical characteristics, echocardiographic features, and overall survival of LFLG AS patients (n 38) to those with normal-flow, low-gradient (NFLG) severe AS (n 75) and moderate AS (n 70). Low-flow, low-gradient patients had the lowest end-diastolic volume index (43 vs. 54 vs. 54 mL/m(2), P 0.001), highest relative wall thickness (RWT) (60 vs. 49 vs. 48, P 0.001), and lowest septal mitral annular displacement (1.0 vs. 1.5 vs. 1.5 cm, P 0.001). New York Heart Association (NYHA) class III/IV symptoms were the most frequent in the LFLG group (29 vs. 11 vs. 3, P 0.001). Survival at 3 years was significantly lower in LFLG compared with NFLG (P 0.006) and moderate AS (P 0.002), but not different between NFLG and moderate AS (P 0.49). Higher NYHA classification (HR 1.77, 95 CI 1.222.57), RWT 50 (HR 3.28, 95 CI 1.338.1), and septal displacement 1.1 cm (HR 3.93, 95 CI 1.967.82) but not low flow were independent predictors of survival in Cox proportional hazards analysis. Preserved ejection fraction, LFLG AS patients exhibit marked concentric remodelling and impaired longitudinal functionalufeatures that predict their poor long-term survival. Normal-flow, low-gradient AS patients have outcomes similar to moderate AS. C1 [Mehrotra, Praveen; Jansen, Katrijn; Flynn, Aidan W.; Tan, Timothy C.; Picard, Michael H.; Hung, Judy] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Mehrotra, Praveen; Jansen, Katrijn; Flynn, Aidan W.; Tan, Timothy C.; Elmariah, Sammy; Picard, Michael H.; Hung, Judy] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Elmariah, Sammy] Massachusetts Gen Hosp, Div Cardiol, Cardiac Catheterizat Lab, Boston, MA 02114 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 FU National Institutes of Health (NIH)/National Heart [R01 HL092101]; Lung and Blood Institute (NHLBI) (JH) FX This work was supported in part by grant R01 HL092101 from National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI) (JH). NR 25 TC 45 Z9 45 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2013 VL 34 IS 25 BP 1906 EP 1914 DI 10.1093/eurheartj/eht094 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 183QD UT WOS:000321831200014 PM 23533186 ER PT J AU Magnusson, M Lewis, GD Ericson, U Orho-Melander, M Hedblad, B Engstrom, G Ostling, G Clish, C Wang, TJ Gerszten, RE Melander, O AF Magnusson, Martin Lewis, Gregory D. Ericson, Ulrika Orho-Melander, Marju Hedblad, Bo Engstrom, Gunnar Ostling, Gerd Clish, Clary Wang, Thomas J. Gerszten, Robert E. Melander, Olle TI A diabetes-predictive amino acid score and future cardiovascular disease SO EUROPEAN HEART JOURNAL LA English DT Article DE Metabolomics; Amino acids; Diabetes; Cardiovascular disease ID HOMEOSTASIS MODEL ASSESSMENT; DIETARY ASSESSMENT METHODS; CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; INSULIN-RESISTANCE; MALMO FOOD; METABOLIC SYNDROME; EVENTS; RISK; SENSITIVITY AB We recently identified a metabolic signature of three amino acids (tyrosine, phenylalanine, and isoleucine) that strongly predicts diabetes development. As novel modifiable targets for intervention are needed to meet the expected increase of cardiovascular disease (CVD) caused by the diabetes epidemic, we investigated whether this diabetes-predictive amino acid score (DM-AA score) predicts development of CVD and its functional consequences. We performed a matched casecontrol study derived from the population-based Malm Diet and Cancer Cardiovascular Cohort (MDC-CC), all free of CVD. During 12 years of follow-up, 253 individuals developed CVD and were matched for age, sex, and Framingham risk score with 253 controls. Amino acids were profiled in baseline plasma samples, using liquid chromatography-tandem mass spectrometry, and relationship to incident CVD was assessed using conditional logistic regression. We further examined whether the amino acid score also correlated with anatomical [intima-media thickness (IMT) and plaque formation] and functional (exercise-induced myocardial ischaemia) abnormalities. Compared with the lowest quartile of the DM-AA score, the odds ratio (95 confidence interval) for incident CVD in subjects belonging to quartiles 2, 3, and 4 was 1.27 (0.722.22), 1.96 (1.073.60), and 2.20 (1.124.31) (P-trend 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (P-trend 0.037) and with the presence of at least one plaque larger than 10 mm(2) (P-trend 0.001). Compared with the lowest quartile of the DM-AA score, the odds ratio (95 confidence interval) for inducible ischaemia in subjects belonging to quartiles 2, 3, and 4 was 3.31 (1.0510.4), 4.24 (1.3613.3), and 4.86 (1.4716.1) (P-trend 0.011), respectively. This study identifies branched-chain and aromatic amino acids as novel markers of CVD development and as an early link between diabetes and CVD susceptibility. C1 [Magnusson, Martin] Skane Univ Hosp, Dept Cardiol, SE-20502 Malmo, Sweden. [Magnusson, Martin; Hedblad, Bo; Engstrom, Gunnar; Ostling, Gerd; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory, Boston, MA USA. [Ericson, Ulrika; Gerszten, Robert E.] Lund Univ, Dept Clin Sci Nutr Epidemiol, Malmo, Sweden. [Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Hedblad, Bo; Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, Malmo, Sweden. [Clish, Clary] Broad Inst & Harvard, Cambridge, MA USA. [Wang, Thomas J.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Wang, Thomas J.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. RP Magnusson, M (reprint author), Skane Univ Hosp, Dept Cardiol, Entrance 35,Floor 2, SE-20502 Malmo, Sweden. EM martin.magnusson@med.lu.se OI Engstrom, Gunnar/0000-0002-8618-9152; Magnusson, Martin/0000-0003-1710-5936 FU Swedish Medical Research Council; Swedish Heart and Lung Foundation; Medical Faculty of Lund University, Skane University Hospital; Albert Pahlsson Research Foundation; Crafoord Foundation; Ernhold Lundstroms Research Foundation; Region Skane; Hulda and Conrad Mossfelt Foundation; Southwest Skanes Diabetes Foundation; King Gustaf V and Queen Victoria Foundation; Lennart Hanssons Memorial Fund, Knut and Alice Wallenberg Foundation; Marianne and Marcus Wallenberg Foundation; NIH [NO1-HC-25195, R01-DK-HL081572, R01-HL-094390, R01-HL-098280, K23-HL091106, 5RC1-HL099692-02]; Leducq Foundation; American Heart Association FX M. M. and O.M. were supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Skane University Hospital, the Albert Pahlsson Research Foundation, the Crafoord Foundation, the Ernhold Lundstroms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the Southwest Skanes Diabetes Foundation, the King Gustaf V and Queen Victoria Foundation, the Lennart Hanssons Memorial Fund, Knut and Alice Wallenberg Foundation, and the Marianne and Marcus Wallenberg Foundation. B.H. was supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Skane University Hospital, and the Ernhold Lundstroms Research Foundation. This work was also supported by NIH contracts NO1-HC-25195, R01-DK-HL081572, R01-HL-094390, R01-HL-098280, K23-HL091106, 5RC1-HL099692-02, the Leducq Foundation, and the American Heart Association. NR 31 TC 47 Z9 49 U1 1 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2013 VL 34 IS 26 BP 1982 EP 1989 DI 10.1093/eurheartj/ehs424 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 183QJ UT WOS:000321831900011 PM 23242195 ER PT J AU Shetty, AK Duckett, SG Ginks, MR Ma, YL Sohal, M Bostock, J Kapetanakis, S Singh, JP Rhode, K Wright, M O'Neill, MD Gill, JS Carr-White, G Razavi, R Rinaldi, CA AF Shetty, Anoop K. Duckett, Simon G. Ginks, Matthew R. Ma, Yinglaing Sohal, Manav Bostock, Julian Kapetanakis, Stam Singh, Jagmeet P. Rhode, Kawal Wright, Matthew O'Neill, Mark D. Gill, Jaswinder S. Carr-White, Gerald Razavi, Reza Rinaldi, Christopher Aldo TI Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Haemodynamics; Imaging; Magnetic resonance imaging ID VENTRICULAR PACING SITES; HEART-FAILURE PATIENTS; ISCHEMIC CARDIOMYOPATHY; CORONARY-SINUS; SEGMENTATION; IMPLANTATION; POSITION; IMPROVEMENT; PREDICTORS; INTERVAL AB Aims Left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT) is largely empirical and operator-dependent. Our aim was to determine whether cardiac magnetic resonance (CMR)-guided CRT may improve the acute and the chronic response. Methods CMR-derived anatomical models and dyssynchrony maps were created for 20 patients. The CMR targets (three latest and results activated segments with <50% scar) were overlaid on to live fluoroscopy. Acute haemodynamic response (AHR) to LV pacing was assessed using an intra-ventricular pressure wire. Chronic CRT response (end-systolic volume reduction >= 15%) was assessed 6 months post-implantation. All patients underwent successful CMR-guided LV lead placement. A CMR target segment was paced in 75% of patients. The mean change in LVdP/dt(max) for the CMR target was +14.2 +/- 12.5 vs. +18.7 +/- 11.9% for the best AHR in any segment and +12.0 +/- 13.8% for the segment based on coronary sinus (CS) venography. Using CMR guidance, the acute responder rate was 60 vs. 50% on the basis of venography. At 6 months 60% of patients were echocardiographic responders. Of the echocardiographic responders, 92% were successfully paced in a CMR target segment compared with only 50% of non-responders (P = 0.04). Conclusion CMR guidance compared well when validated against the AHR. Lead placement was possible in the CMR target region in most patients with an AHR comparable with the best achieved in any CS branch. The chronic response was significantly better in patients paced in a CMR target segment. These results suggest that CMR guidance may represent a clinically useful tool for CRT. C1 [Shetty, Anoop K.; Duckett, Simon G.; Ginks, Matthew R.; Ma, Yinglaing; Sohal, Manav; Rhode, Kawal; Wright, Matthew; O'Neill, Mark D.; Gill, Jaswinder S.; Razavi, Reza; Rinaldi, Christopher Aldo] Kings Coll London, Rayne Inst, Dept Imaging Sci, London WC2R 2LS, England. [Shetty, Anoop K.; Duckett, Simon G.; Ginks, Matthew R.; Sohal, Manav; Bostock, Julian; Kapetanakis, Stam; Wright, Matthew; O'Neill, Mark D.; Gill, Jaswinder S.; Carr-White, Gerald; Rinaldi, Christopher Aldo] Guys & St Thomas NHS Fdn Trust, Cardiothorac Dept, London, England. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02459 USA. RP Shetty, AK (reprint author), St Thomas Hosp, 6th Floor,East Wing, London SE1 7EH, England. EM anoopshetty@doctors.org.uk OI Bostock, Julian/0000-0003-2418-4388; Shetty, Anoop/0000-0002-0365-0071; Wright, Matthew/0000-0002-0541-7556 FU King's College London; Guys and St Thomas' Hospital NHS Foundation Trust FX This study was funded by King's College London and Guys and St Thomas' Hospital NHS Foundation Trust. NR 36 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD JUL PY 2013 VL 14 IS 7 BP 692 EP 699 DI 10.1093/ehjci/jes270 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 178QN UT WOS:000321462600014 PM 23175695 ER PT J AU Hoexter, MQ Dougherty, DD Shavitt, RG D'Alcante, CC Duran, FLS Lopes, AC Diniz, JB Batistuzzo, MC Evans, KC Bressan, RA Busatto, GF Miguel, EC AF Hoexter, Marcelo Q. Dougherty, Darin D. Shavitt, Roseli G. D'Alcante, Carina C. Duran, Fabio L. S. Lopes, Antonio C. Diniz, Juliana B. Batistuzzo, Marcelo C. Evans, Karleyton C. Bressan, Rodrigo A. Busatto, Geraldo F. Miguel, Euripedes C. TI Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE OCD; Neuroimaging; Gray matter; Serotonergic reuptake inhibitor; Cognitive-behavioral therapy ID SEROTONIN REUPTAKE INHIBITORS; GLUCOSE METABOLIC-RATE; MAJOR DEPRESSION; CLINICAL-TRIAL; ANTERIOR CINGULATE; CORTEX; BRAIN; EXTINCTION; PREDICTORS; PAROXETINE AB Nearly one-third of patients with obsessive-compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naive OCD patients randomized between trials of fluoxetine or CBI Treatment-naive OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602. (C) 2012 Elsevier B.V. and ECNP. All rights reserved. C1 [Hoexter, Marcelo Q.; Shavitt, Roseli G.; D'Alcante, Carina C.; Duran, Fabio L. S.; Lopes, Antonio C.; Diniz, Juliana B.; Batistuzzo, Marcelo C.; Busatto, Geraldo F.; Miguel, Euripedes C.] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, BR-05403010 Sao Paulo, Brazil. [Hoexter, Marcelo Q.; Bressan, Rodrigo A.] Fed Univ Sao Paulo UNIFESP, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, Sao Paulo, Brazil. [Hoexter, Marcelo Q.; Dougherty, Darin D.; Evans, Karleyton C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Hoexter, MQ (reprint author), Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, Rua Ovidio Pires Campos 785-3 Andar Ala Norte Sal, BR-05403010 Sao Paulo, Brazil. EM mqhoexter@gmail.com RI Duran, Fabio/L-1371-2013; Busatto, Geraldo/D-4431-2009; Duran, Fabio/I-5704-2012; Bressan, Rodrigo/E-9178-2010; Hoexter, Marcelo/D-7620-2013; Batistuzzo, Marcelo/H-7790-2015 OI Duran, Fabio/0000-0002-7603-6152; Duran, Fabio/0000-0003-2494-7250; Bressan, Rodrigo/0000-0002-0868-4449; Hoexter, Marcelo/0000-0002-9302-4380; FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo [2005/55628-8]; FAPESP scholarships [06/61459-7, 06/50273-0, 2008/10257-0, 06/58286-3]; FAPESP [2005/04206-6]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) (4375/08-4 [4375/08-4] FX This study received financial support in the form of Grants provided by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) to Dr. Miguel (2005/55628-8) and from FAPESP scholarships to Dr. Shavitt (06/61459-7), to Dr. Diniz (06/50273-0), to Dr. Lopes (2008/10257-0), and to Ms. D'Alcante (06/58286-3). Dr. Hoexter is supported by a Ph.D. scholarship from FAPESP (2005/04206-6) and by a doctorate "sandwich" scholarship from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Agency for Support and Evaluation of Graduate Education) (4375/08-4). NR 57 TC 16 Z9 18 U1 3 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JUL PY 2013 VL 23 IS 7 BP 569 EP 580 DI 10.1016/j.euroneuro.2012.06.014 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 173MN UT WOS:000321083700002 PM 22841131 ER PT J AU Kloiber, S Ripke, S Kohli, MA Reppermund, S Salyakina, D Uher, R McGuffin, P Perlis, RH Hamilton, SP Putz, B Hennings, J Bruckl, T Klengel, T Bettecken, T Ising, M Uhr, M Dose, T Unschuld, PG Zihl, J Binder, E Muller-Myhsok, B Holsboer, F Lucae, S AF Kloiber, Stefan Ripke, Stephan Kohli, Martin A. Reppermund, Simone Salyakina, Daria Uher, Rudolf McGuffin, Peter Perlis, Roy H. Hamilton, Steven P. Puetz, Benno Hennings, Johannes Brueckl, Tanja Klengel, Torsten Bettecken, Thomas Ising, Marcus Uhr, Manfred Dose, Tatjana Unschuld, Paul G. Zihl, Josef Binder, Elisabeth Mueller-Myhsok, Bertram Holsboer, Florian Lucae, Susanne TI Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Depression; Leptin; Treatment response; Gene expression; Pharmacogenetics ID PITUITARY-ADRENAL AXIS; MAJOR DEPRESSION; MOOD DISORDERS; PLASMA LEPTIN; BODY-WEIGHT; STRESS; OBESITY; GENDER; SYSTEM; GENOME AB Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9 x 10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant therapy in depressed patients. (C) 2012 Elsevier B.V. and ECNP. All rights reserved. C1 [Kloiber, Stefan; Puetz, Benno; Hennings, Johannes; Brueckl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Zihl, Josef; Binder, Elisabeth; Mueller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Ripke, Stephan] MGH Simches Res Ctr, Ctr Human Genet Res, Boston, MA USA. [Kohli, Martin A.; Salyakina, Daria] John P Hussman Inst Human Genom, Miami, FL USA. [Reppermund, Simone] Univ New S Wales, Sch Psychiat, Randwick, NSW, Australia. [Uher, Rudolf; McGuffin, Peter] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. [Hamilton, Steven P.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Hamilton, Steven P.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Unschuld, Paul G.] Johns Hopkins Univ, Baltimore, MD USA. RP Kloiber, S (reprint author), Max Planck Inst Psychiat, Kraepelinstr 2-10, D-80804 Munich, Germany. EM stkloiber@mpipsykl.mpg.de RI Klengel, Torsten/E-5629-2010; Putz, Benno/P-2630-2016; McGuffin, Peter/A-1565-2012; Unschuld, Paul/N-7294-2013; Uher, Rudolf/A-5477-2008; OI Putz, Benno/0000-0002-2208-209X; Josef, Zihl/0000-0002-0838-0103; McGuffin, Peter/0000-0002-9888-2907; Uher, Rudolf/0000-0002-2998-0546; Kloiber, Stefan/0000-0002-6838-4114; Klengel, Torsten/0000-0001-7045-9229; Hamilton, Steven/0000-0001-8106-6260 FU Max Planck Society; German Federal Ministry for Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN2 and NGFN-Plus) [FKZ 01GSO481]; BMBF Program [01ES0811]; NIMH [N01 MH-90003, R01 MH-072802]; European Commission [LSHB-CT-2003-503428]; Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and South London; Maudsley National Health Service Foundation Trust (National Institute for Health Research, United Kingdom); Medical Research Council, United Kingdom [G0701420] FX The MARS-Study was funded by the Max Planck Society and in part by a research grant from the German Federal Ministry for Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN2 and NGFN-Plus, FKZ 01GSO481) and by the BMBF Program "Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression" (01ES0811). The authors' research on personalized medicine is supported by the Max Planck Excellence Foundation.; The STAR*D study was supported by funds from NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (A. John Rush, M.D., Genotyping of STAR*D samples was funded by NIMH (R01 MH-072802; Steven R Hamilton, M.D., Ph.D., RI.).; The GENDEP project was supported by a European Commission Framework 6 grant (contract reference: LSHB-CT-2003-503428), the Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and South London, and the Maudsley National Health Service Foundation Trust (National Institute for Health Research, United Kingdom) and the Medical Research Council, United Kingdom (G0701420). NR 43 TC 14 Z9 15 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JUL PY 2013 VL 23 IS 7 BP 653 EP 662 DI 10.1016/j.euroneuro.2012.08.010 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 173MN UT WOS:000321083700011 PM 23026132 ER PT J AU Li, G Shih, YYI Kiel, JW De La Garza, BH Du, F Duong, TQ AF Li, Guang Shih, Yen-Yu Ian Kiel, Jeffrey W. De La Garza, Bryan H. Du, Fang Duong, Timothy Q. TI MRI study of cerebral, retinal and choroidal blood flow responses to acute hypertension SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE cASL MRI; retina; choroid; blood pressure; blood flow; baroregulation; autoregulation ID FUNCTIONAL MRI; PARASYMPATHETIC NERVES; INTRAOCULAR-PRESSURE; ARTERIAL-PRESSURE; MOUSE MODEL; IN-VIVO; AUTOREGULATION; DIFFUSION; BRAIN; RAT AB Blood flow (BF) in many tissues is stable during significant fluctuations in systemic arterial blood pressure or perfusion pressure under normal conditions. The regulatory mechanisms responsible for this non-passive BF behavior include both local and neural control mechanisms. This study evaluated cerebral BF (CBF), retinal BF (RBF) and choroidal BF (ChBF) responses to acute blood pressure increases in rats using magnetic resonance imaging (MRI). A transient increase in blood pressure inside the MRI scanner was achieved by mechanically inflating a balloon catheter to occlude the descending aorta near the diaphragm. We verified the rat model of mechanical occlusion and MRI approach by first measuring blood-flow regulatory responses to changing BP in the brain under normoxia and hypercapnia where the phenomenon is well documented. Retinal and choroidal blood-flow responses to transient increased arterial pressure were then investigated. In response to an acute increase in blood pressure, RBF exhibited autoregulatory behavior and ChBF exhibited baroregulation similar to that seen in the cerebral circulation. This approach may prove useful to investigate retinal and choroidal vascular dysregulation in rat models of retinal diseases with suspected vascular etiology. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; OI Shih, Yen-Yu Ian/0000-0001-6529-911X FU NIH/NEI [R01 EY014211, EY018855, EY009702]; Department of Veterans Affairs; San Antonio Life Science Institute; American Heart Association [10POST4290091]; CTSA/RII imaging supplement awards [CTSA-004A, CTSA-008A]; San Antonio Area Foundation FX This work was supported in part by the NIH/NEI (R01 EY014211, EY018855 and EY009702), MERIT Award from the Department of Veterans Affairs, and San Antonio Life Science Institute to TQD and American Heart Association (10POST4290091), CTSA/RII imaging supplement awards (CTSA-004A and CTSA-008A), and San Antonio Area Foundation to YYIS. NR 41 TC 6 Z9 6 U1 0 U2 8 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 JUL PY 2013 VL 112 BP 118 EP 124 DI 10.1016/j.exer.2013.04.003 PG 7 WC Ophthalmology SC Ophthalmology GA 180OS UT WOS:000321605100014 PM 23623996 ER PT J AU Nabors, LK Wang, LD Wagers, AJ Kansas, GS AF Nabors, L. Karina Wang, Leo D. Wagers, Amy J. Kansas, Geoffrey S. TI Overlapping roles for endothelial selectins in murine hematopoietic stem/progenitor cell homing to bone marrow SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID GLYCOPROTEIN LIGAND 1; ROLLING IN-VIVO; CD8(+) T-CELLS; P-SELECTIN; ADHESION MOLECULE-1; DEFICIENT MICE; LEUKOCYTE ADHESION; PROGENITOR CELLS; PLASMA-CELLS; STEM-CELLS AB Selectins are carbohydrate-binding adhesion molecules that are critically involved in leukocyte recognition of endothelium. The endothelial selectins have been implicated in homing of hematopoietic stem and progenitor cells (HSPCs) to the bone marrow (BM) during bone marrow transplant (BMT), but the precise roles of individual selectins in this process have never been defined. BMT of lethally irradiated mice lacking both endothelial selectins (E/P KO) with limiting numbers of wild type BM cells rescued significantly fewer E/P KO than WT recipients, but higher numbers of transplanted WT cells rescued E/P KOs in a dose-dependent fashion. Short-term homing assays confirmed a substantial defect in HSPC homing to BM in E/P KO mice. In contrast, BMT of E-selectin null or P-selectin null mice at limiting cell number uniformly rescued greater than 95% of the transplanted animals. Consistent with these functional results, flow cytometric analysis revealed both E-selectin ligands and P-selectin ligands on distinct subsets of HSPC. These results demonstrate overlapping functions for the endothelial selectins in HSPC homing to BM in the setting of BMT, and define a novel aspect of HSPC heterogeneity linked to selectin ligand expression. (C) 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Nabors, L. Karina; Kansas, Geoffrey S.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. [Wang, Leo D.; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wang, Leo D.; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wang, Leo D.] Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Wagers, Amy J.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. RP Kansas, GS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, 320 East Super Avenure, Chicago, IL 60611 USA. EM gsk@northwestern.edu FU National Institutes of Health [NIH] [P30DK036836, HL058710, 1RO1 HL088582, DP2 OD004345, 5T32 HL007574]; Damon Runyon Cancer Research Foundation [DRSG 2-12]; St. Baldrick's Foundation FX The authors thank Joslin's HSCI/DERC Flow Cytomety Core (National Institutes of Health [NIH] Award Number P30DK036836) for excellent flow cytometry support and H. Ziltener for helpful advice during preparation of the manuscript.; A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. L.D.W. is a Damon Runyon-Sohn Foundation Fellow supported by the Damon Runyon Cancer Research Foundation (DRSG 2-12) and the St. Baldrick's Foundation. This work was supported by NIH grants HL058710 to GSK, 1RO1 HL088582, and DP2 OD004345 (to A.J.W.) and 5T32 HL007574 (to L.D.W.). NR 49 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2013 VL 41 IS 7 BP 588 EP 596 DI 10.1016/j.exphem.2013.02.014 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 181RE UT WOS:000321685400002 PM 23499761 ER PT J AU Takalo, M Haapasalo, A Natunen, T Viswanathan, J Kurkinen, KMA Tanzi, RE Soininen, H Hiltunen, M AF Takalo, Mari Haapasalo, Annakaisa Natunen, Teemu Viswanathan, Jayashree Kurkinen, Kaisa M. A. Tanzi, Rudolph E. Soininen, Hilkka Hiltunen, Mikko TI Targeting ubiquilin-1 in Alzheimer's disease SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE aggresome; Alzheimer's disease; amyloid precursor protein; autophagy; beta-amyloid; endoplasmic reticulum stress; presenilin; proteasome; secretase; ubiquitin-associated domain; ubiquitin-like domain ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE ACTIVITY; ENDOPLASMIC-RETICULUM; GENETIC ASSOCIATION; AGGRESOME FORMATION; DEGRADATION; UBQLN1; CELL; UBIQUITINATION; PRESENILIN AB Introduction: Alzheimer's disease (AD) is a common neurodegenerative disorder affecting an increasing number of people worldwide as the population ages. Currently, there are no drugs available that could prevent AD pathogenesis or slow down its progression. Increasing evidence links ubiquilin-1, an ubiquitin-like protein, into the pathogenic mechanisms of AD and other neurodegenerative diseases. Ubiquilin-1 has been shown to play a key role in the regulation of the levels, subcellular targeting, aggregation and degradation of various neurodegenerative disease-associated proteins. These include the amyloid precursor protein and presenilins that are intimately involved in the mechanisms of AD. Areas covered: Here, the properties and diverse functions of ubiquilin-1 protein in the context of the pathogenesis of AD and other neurodegenerative disorders are discussed. This review recapitulates the available knowledge on the involvement of ubiquilin-1 in the genetic and molecular mechanisms in AD. Furthermore, the association of ubiquilin-1 with specific proteins and mechanisms involved in the pathogenesis of neurodegenerative diseases is described and the known ubiquilin-1-interacting proteins summarized. Expert opinion: The variety of ubiquilin-1-interacting proteins and its central role in the regulation of protein levels and degradation provides a number of novel candidates and approaches for future research and drug discovery. C1 [Takalo, Mari; Haapasalo, Annakaisa; Natunen, Teemu; Viswanathan, Jayashree; Kurkinen, Kaisa M. A.] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio 70211, Finland. [Takalo, Mari; Haapasalo, Annakaisa; Natunen, Teemu; Viswanathan, Jayashree] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. [Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Boston, MA 02129 USA. [Soininen, Hilkka; Hiltunen, Mikko] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio Univ Hosp, Dept Neurol, Kuopio 70211, Finland. RP Hiltunen, M (reprint author), Univ Eastern Finland, Inst Clin Med Neurol, Kuopio Univ Hosp, Dept Neurol, POB 1627, Kuopio 70211, Finland. EM mikko.hiltunen@uef.fi OI Chadchankar, Jayashree/0000-0002-0189-569X FU Health Research Council of the Academy of Finland; EVO of Kuopio University Hospital [5772708]; Strategic Funding of the University on Eastern Finland (UEF-Brain); Sigrid Juselius Foundation FX This study was supported by the Health Research Council of the Academy of Finland, EVO grant 5772708 of Kuopio University Hospital, the Strategic Funding of the University on Eastern Finland (UEF-Brain) and Sigrid Juselius Foundation. The authors state no conflict of interest and have received no payment in preparation of this manuscript. NR 76 TC 6 Z9 7 U1 0 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JUL PY 2013 VL 17 IS 7 BP 795 EP 810 DI 10.1517/14728222.2013.791284 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180NT UT WOS:000321602600006 PM 23600477 ER PT J AU Haberer, JE Trabin, T Klinkman, M AF Haberer, Jessica E. Trabin, Tom Klinkman, Michael TI Furthering the reliable and valid measurement of mental health screening, diagnoses, treatment and outcomes through health information technology SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Mental health; Information technology; Measurement ID RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY ADHERENCE; DEPRESSION RATING-SCALE; SELF-REPORTED ADHERENCE; MEASUREMENT-BASED CARE; STAR-ASTERISK-D; PSYCHOLOGICAL-ASSESSMENT; MEDICATION ADHERENCE; CLINICAL-PRACTICE; MAJOR DEPRESSION AB Introduction: Measurement of mental health is challenging; however, many solutions may be found through the use of health information technology. Method: This article reviews current approaches to measuring mental health, focusing on screening, diagnosis, treatment, and outcomes. It then identifies several key areas in which health information technology may advance the field and provide reliable and valid measurements that are readily available to and manageable for providers, as well as acceptable, feasible, and sustainable for selected populations. Result and Conclusions: Although new technologies must overcome many challenges, including privacy, efficiency, cost, and scalability, it is an exciting and fast-growing field with many potential applications and clinical benefit. (C) 2013 Elsevier Inc. All rights reserved. C1 [Haberer, Jessica E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA. [Trabin, Tom] Alameda Cty Behav Hlth Care Serv, Alameda, CA USA. [Klinkman, Michael] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. RP Haberer, JE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jhaberer@partners.org FU ARHQ [290-09-00036U]; [K23MH087228] FX This work was funded by ARHQ contract #290-09-00036U and K23MH087228. NR 82 TC 6 Z9 6 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2013 VL 35 IS 4 BP 349 EP 353 DI 10.1016/j.genhosppsych.2013.03.009 PG 5 WC Psychiatry SC Psychiatry GA 173UU UT WOS:000321107600005 PM 23628162 ER PT J AU Chen, H Chen, K AF Chen, Hua Chen, Kun TI Asymptotic Distributions of Coalescence Times and Ancestral Lineage Numbers for Populations with Temporally Varying Size SO GENETICS LA English DT Article ID ALLELE-FREQUENCY-SPECTRUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; SEGREGATING SITES; NEUTRAL ALLELES; SAMPLING THEORY; GENETIC DRIFT; HUMAN GENOME; OF-DESCENT; INFERENCE; SELECTION AB The distributions of coalescence times and ancestral lineage numbers play an essential role in coalescent modeling and ancestral inference. Both exact distributions of coalescence times and ancestral lineage numbers are expressed as the sum of alternating series, and the terms in the series become numerically intractable for large samples. More computationally attractive are their asymptotic distributions, which were derived in Griffiths (1984) for populations with constant size. In this article, we derive the asymptotic distributions of coalescence times and ancestral lineage numbers for populations with temporally varying size. For a sample of size n, denote by T-m the mth coalescent time, when m + 1 lineages coalesce into m lineages, and A(n)(t) the number of ancestral lineages at time t back from the current generation. Similar to the results in Griffiths (1984), the number of ancestral lineages, A(n)(t), and the coalescence times, T-m, are asymptotically normal, with the mean and variance of these distributions depending on the population size function, N(t). At the very early stage of the coalescent, when t -> 0, the number of coalesced lineages n - A(n)(t) follows a Poisson distribution, and as m -> n, n(n - 1)T-m/2N(0) follows a gamma distribution. We demonstrate the accuracy of the asymptotic approximations by comparing to both exact distributions and coalescent simulations. Several applications of the theoretical results are also shown: deriving statistics related to the properties of gene genealogies, such as the time to the most recent common ancestor (TMRCA) and the total branch length (TBL) of the genealogy, and deriving the allele frequency spectrum for large genealogies. With the advent of genomic-level sequencing data for large samples, the asymptotic distributions are expected to have wide applications in theoretical and methodological development for population genetic inference. C1 [Chen, Hua] Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. [Chen, Kun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, H (reprint author), Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. EM hchen007@gmail.com NR 47 TC 7 Z9 8 U1 0 U2 5 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 1943-2631 J9 GENETICS JI Genetics PD JUL PY 2013 VL 194 IS 3 BP 721 EP + DI 10.1534/genetics.113.151522 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA 175TI UT WOS:000321255800016 PM 23666939 ER PT J AU Gold, MR Yu, YH Singh, JP Stein, KM Birgersdotter-Green, U Meyer, TE Seth, M Ellenbogen, KA AF Gold, Michael R. Yu, Yinghong Singh, Jagmeet P. Stein, Kenneth M. Birgersdotter-Green, Ulrika Meyer, Timothy E. Seth, Milan Ellenbogen, Kenneth A. TI The effect of left ventricular electrical delay on AV optimization for cardiac resynchronization therapy SO HEART RHYTHM LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Electrical dyssynchrony; LV pacing site; Left ventricular reverse remodeling; Outcomes ID HEART-FAILURE PATIENTS; LEAD POSITION; TRIAL; REVERSE; CONDUCTION; DEFIBRILLATOR; IMPLANTATION; DYSFUNCTION; ASYNCHRONY; SURVIVAL AB BACKGROUND The role of atrioventricular optimization (AVO) for cardiac resynchronization therapy (CRT) is controversial. Identifying subgroups that benefit from optimization is important to improve CRT outcomes. Pacing at sites of late electrical activation, as assessed by the QLV interval, improves remodeling with CRT. OBJECTIVE To evaluate whether pacing at sites of long left ventricular (LV) electrical delay increases the effectiveness of AVO. METHODS This substudy of the SMART-AV trial included 280 subjects who were randomized to either an electrogram-based AVO (SmartDelay) or nominal atrioventricular delay (120 ms). The QLV interval was defined as the time from the onset of QRS to the LV electrogram peak. CRT response was defined prospectively as a >15% reduction in left ventricular end systolic volume from implant to 6 months. RESULTS The cohort was 68% men, with a mean age of 66 +/- 11 years and LV ejection fraction of 28% +/- 8%. Longer QLV durations were significantly associated with CRT response (P < .01) for the entire cohort. Moreover, the benefit of AVO increased as QLV prolonged. At the longest QLV quartile, there was more than a 6-fold increase in the likelihood of a remodeling response compared with nominal atrioventricular delays. CONCLUSIONS Baseline electrical dyssynchrony, as measured by the QLV interval, predicted CRT response. At long QLV intervals, AVO can increase the likelihood of structural response to CRT. AVO and QLV optimized that LV lead location may work synergistically to maximize CRT response. C1 [Gold, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Yu, Yinghong; Stein, Kenneth M.; Meyer, Timothy E.; Seth, Milan] Boston Sci, St Paul, MN USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birgersdotter-Green, Ulrika] Univ Calif San Diego, San Diego, CA 92103 USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. RP Gold, MR (reprint author), Med Univ S Carolina, 25 Courtenay Dr,ART 7031, Charleston, SC 29425 USA. EM goldmr@musc.edu FU Boston Scientific Corporation; Boston Scientific; Medtronic; St Jude Medical; Sorin; Sorin Group; Biotronik; Cameron; Biosense Webster; Sanofi FX This study was funded by Boston Scientific Corporation. Dr Gold has received consulting fees and research grants from Boston Scientific, Medtronic, St Jude Medical, and Sorin as well as speaking fees from Sorin Group and Biotronik. Dr Singh has received research grants from St Jude Medical, Medtronic, Boston Scientific, and Biotronik; he is a member of the advisory board/steering committee/consultant at Boston Scientific, Biotronik, St Jude Medical, Medtronic, CardioInsight, Thoratec, and Biosense Webster; he has also received honoraria/speaker fees from Medtronic, Biotronik, Boston Scientific, St Jude Medical, and Sorin. Dr Birgersdotter-Green has received speakers bureau and research grants from Medtronic and St Jude Medical and honorarium from Biotronik. Mr Yu, Dr Stein, Dr Meyer, and Mr Seth are employees of Boston Scientific. Dr Ellenbogen has received consulting fees and honoraria from Medtronic, Boston Scientific, and Cameron; speakers bureau from Medtronic, Boston Scientific, St Jude Medical, Biotronik, and Sanofi; research grants from Medtronic, Boston Scientific, Biosense Webster, and Sanofi; and fellowship support from Medtronic, Boston Scientific, and Biosense Webster. NR 35 TC 11 Z9 11 U1 1 U2 3 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 JUL PY 2013 VL 10 IS 7 BP 988 EP 993 DI 10.1016/j.hrthm.2013.03.009 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 179DA UT WOS:000321497500009 PM 23499621 ER PT J AU Huertas-Vazquez, A Teodorescu, C Reinier, K Uy-Evanado, A Chugh, H Jerger, K Ayala, J Gunson, K Jui, J Newton-Cheh, C Albert, CM Chugh, SS AF Huertas-Vazquez, Adriana Teodorescu, Carmen Reinier, Kyndaron Uy-Evanado, Audrey Chugh, Harpriya Jerger, Katherine Ayala, Jo Gunson, Karen Jui, Jonathan Newton-Cheh, Christopher Albert, Christine M. Chugh, Sumeet S. TI A common missense variant in the neuregulin 1 gene is associated with both schizophrenia and sudden cardiac death SO HEART RHYTHM LA English DT Article DE Sudden cardiac death; Association study; Genetic; Schizophrenia; Epilepsy; Neuregulin 1 ID GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; PSYCHIATRIC-PATIENTS; UNEXPECTED DEATH; RISK; POPULATION; EPILEPSY; SUSCEPTIBILITY; IDENTIFICATION; ARREST AB BACKGROUND Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD. OBJECTIVE To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy. METHODS From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for the association between 17 single-nucleotide polymorphisms (SNPs) mapped to 14 loci previously implicated in schizophrenia and epilepsy by using logistic regression and assuming additive, dominant, and recessive genetic models. RESULTS The minor allele of the nonsynonymous SNP rs10503929 within the neuregulin 1 gene was associated with SCD under all 3 investigated models, with the strongest association for the recessive genetic model (recessive P = 4.01 x 10(-5), odds ratio [OR] 4.04; additive P = 2.84 x 10(-7), OR 1.9; and dominant P = 9.01 x 10(-6), OR 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P = .0005, OR 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown. CONCLUSIONS The observed association between a schizophrenia-related neuregulin 1 gene variant and SCD may represent the first evidence of coexisting genetic susceptibility between 2 conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD. C1 [Huertas-Vazquez, Adriana; Teodorescu, Carmen; Reinier, Kyndaron; Uy-Evanado, Audrey; Chugh, Harpriya; Jerger, Katherine; Ayala, Jo; Chugh, Sumeet S.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. [Gunson, Karen; Jui, Jonathan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Albert, Christine M.] Harvard Univ, Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Div Prevent Med,Cardiovasc Div,Dept Med,Sch Med, Boston, MA 02115 USA. RP Chugh, SS (reprint author), Cedars Sinai Med Ctr, Inst Heart, Saperstein 2S46,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM sumeet.chugh@cshs.org FU National Heart, Lung, and Blood Institute [HL068070, HL-34595, HL-26490, HL-34594, HL-35464, HL-46959, HL-080467]; National Cancer Institute [CA34944, CA40360, CA55075, CA87969, CA97193]; Career Award for Medical Scientists from the Burroughs Wellcome Fund FX Dr Chugh holds the Pauline and Harold Price Endowed Chair in Cardiac Electrophysiology at Cedars-Sinai Medical Center. The Harvard Cohort SCD study was supported by grants HL068070, HL-26490, HL-34595, HL-34594, HL-35464, HL-46959, and HL-080467 from the National Heart, Lung, and Blood Institute and CA34944, CA40360, CA55075, CA87969, and CA97193 from the National Cancer Institute and by a Career Award for Medical Scientists from the Burroughs Wellcome Fund. NR 35 TC 13 Z9 13 U1 2 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 JUL PY 2013 VL 10 IS 7 BP 994 EP 998 DI 10.1016/j.hrthm.2013.03.020 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 179DA UT WOS:000321497500010 PM 23524320 ER PT J AU Sayadi, O Shamsollahi, MB AF Sayadi, Omid Shamsollahi, Mohammad Bagher TI Utility of a Nonlinear Joint Dynamical Framework to Model a Pair of Coupled Cardiovascular Signals SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Arterial blood pressure (ABP); electrocardiogram; extended Kalman filter; Gaussian mixture model (GMM); joint dynamical model; pulse transit time (PTT) ID PULSE TRANSIT-TIME; EXTENDED KALMAN FILTER; BLOOD-PRESSURE; HEART-RATE; ECG; COMPRESSION; RESPIRATION; VARIABILITY; ANESTHESIA; DISEASE AB We have recently proposed a correlated model to provide a Gaussian mixture representation of the cardiovascular signals, with promising results in identifying rhythm disturbances. The approach provides a transformation of the data into a set of integrable Gaussians distributed over time. Looking into the model from a new joint modeling perspective, it is capable of assembling a filtered estimation, and can be used to derive temporal information of the waveforms. In this paper, we present a step-by-step derivation of the joint model putting correlation assumptions together to conclude a minimal joint description for a pair of ECG-ABP signals. We then probe novel applications of this model, including Kalman filter based denoising and fiducial point detection. In particular, we use the joint model for denoising and employ the de-noised signals for pulse transit time (PTT) estimation. We analyzed more than 70 h of data from 76 patients from the MIMIC database to illustrate the accuracy of the algorithm. We have found that this method can be effectively used for robust joint ECG-ABP noise suppression, with mean signal-to-noise ratio (SNR) improvement up to 23.2 (12.0) dB and weighted diagnostic distortion measures as low as 2.1 (3.3)% for artificial (real) noises, respectively. In addition, we have estimated the error distributions for QT interval, systolic and diastolic blood pressure before and after filtering to demonstrate the maximal preservation of morphological features (Delta QT: mean +/- std = 2.2 +/- 6.1 ms; Delta SBP: mean +/- std = 2.3 +/- 1.9 mmHg; Delta DBP: mean +/- std = 1.9 +/- 1.4 mmHg). Finally, we have been able to present a systematic approach for robust PTT estimation (r = 0.98, p < 0.001, mean +/- std of error = -0.26 +/- 2.93 ms). These findings may have important implications for reliable monitoring and estimation of clinically important features in clinical settings. In conclusion, the proposed framework opens the door to the possibility of deploying a hybrid system that integrates these algorithmic approaches for index estimation and filtering scenarios with high output SNRs and low distortion. C1 [Sayadi, Omid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Shamsollahi, Mohammad Bagher] Sharif Univ Technol, Sch Elect Engn, Biomed Signal & Image Proc Lab, Tehran 113659363, Iran. RP Sayadi, O (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. EM osayadi@ieee.org; mbshams@sharif.edu FU Departmental Research Assistant Scholarship [RA-86300384]; Exceptional Talents Center, Sharif University of Technology, Tehran, Iran; School of Electrical Engineering, Sharif University of Technology, Tehran, Iran FX This work was supported by the Departmental Research Assistant Scholarship #RA-86300384 granted by the School of Electrical Engineering, Sharif University of Technology, Tehran, Iran, and by a Research Award from the Exceptional Talents Center, Sharif University of Technology, Tehran, Iran. NR 60 TC 1 Z9 1 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD JUL PY 2013 VL 17 IS 4 BP 881 EP 890 DI 10.1109/JBHI.2013.2263836 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 175GK UT WOS:000321218700016 PM 25055317 ER PT J AU Weller, DS Polimeni, JR Grady, L Wald, LL Adalsteinsson, E Goyal, VK AF Weller, Daniel S. Polimeni, Jonathan R. Grady, Leo Wald, Lawrence L. Adalsteinsson, Elfar Goyal, Vivek K. TI Sparsity-Promoting Calibration for GRAPPA Accelerated Parallel MRI Reconstruction SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Compressed sensing; image reconstruction; magnetic resonance imaging; parallel imaging ID IMAGING RECONSTRUCTION; K-SPACE; REGULARIZATION; RECOVERY; SENSE AB The amount of calibration data needed to produce images of adequate quality can prevent auto-calibrating parallel imaging reconstruction methods like generalized autocalibrating partially parallel acquisitions (GRAPPA) from achieving a high total acceleration factor. To improve the quality of calibration when the number of auto-calibration signal (ACS) lines is restricted, we propose a sparsity-promoting regularized calibration method that finds a GRAPPA kernel consistent with the ACS fit equations that yields jointly sparse reconstructed coil channel images. Several experiments evaluate the performance of the proposed method relative to unregularized and existing regularized calibration methods for both low-quality and underdetermined fits from the ACS lines. These experiments demonstrate that the proposed method, like other regularization methods, is capable of mitigating noise amplification, and in addition, the proposed method is particularly effective at minimizing coherent aliasing artifacts caused by poor kernel calibration in real data. Using the proposed method, we can increase the total achievable acceleration while reducing degradation of the reconstructed image better than existing regularized calibration methods. C1 [Weller, Daniel S.] Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Grady, Leo] HeartFlow, Redwood City, CA 94063 USA. [Adalsteinsson, Elfar; Goyal, Vivek K.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Weller, DS (reprint author), Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. EM dweller@alum.mit.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU National Science Foundation (NSF) [0643836]; National Institutes of Health (NIH) [NIH R01 EB007942, EB006847, NIH P41 RR014075, NIH K01 EB011498, NIH F32 EB015914]; Siemens Healthcare; NSF FX This work was supported by the National Science Foundation (NSF) under CAREER grant 0643836, in part the National Institutes of Health (NIH) under Grant NIH R01 EB007942 and EB006847, Grant NIH P41 RR014075, Grant NIH K01 EB011498, and Grant NIH F32 EB015914, in part by Siemens Healthcare, and in part by a NSF Graduate Research Fellowship. Asterisk indicates corresponding author. NR 29 TC 5 Z9 5 U1 1 U2 14 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2013 VL 32 IS 7 BP 1325 EP 1335 DI 10.1109/TMI.2013.2256923 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 175HA UT WOS:000321220300014 PM 23584259 ER PT J AU Nelson, BD Stoklosa, H Ahn, R Eckardt, MJ Walton, EK Burke, TF AF Nelson, Brett D. Stoklosa, Hanni Ahn, Roy Eckardt, Melody J. Walton, Emily K. Burke, Thomas F. TI Use of uterine balloon tamponade for control of postpartum hemorrhage by community-based health providers in South Sudan SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Low-resource countries; Maternal health; Midwifery; Postpartum hemorrhage; Traditional birth attendant; Uterine balloon tamponade ID MANAGEMENT; COUNTRIES AB Objective: To determine whether use of uterine balloon tamponade (UBT) for management of uncontrolled postpartum hemorrhage (PPH) by community-based providers in a resource-limited setting could be feasible, effective, and safe. Methods: In rural South Sudan, community providers were trained and equipped with a simple UBT device consisting of a catheter, condom, and syringe. Snowball sampling identified cases of UBT use since training. Semi-structured interviews were conducted among community providers, referral facility providers, patients, and patient family members. Interview transcripts were analyzed using qualitative methods. Results: Thirteen cases were identified and 24 interviews related to community-based UBT use were conducted. Qualitative analysis revealed several major themes. Community providers applied UBT in appropriate clinical situations. UBT was effective for controlling PPH, even among severely ill patients. Referral was difficult and lengthy owing to the austere setting, but simple UBT appeared to mitigate these challenges. Communities had some initial fears, yet ultimately embraced UBT. Equipment and supplies were largely maintained. There was universal satisfaction with UBT among patients, family members, and providers. One death occurred among the 13 cases, although it was probably not attributable to PPH. Conclusion: Training and UBT device provision are simple, affordable, and effective for managing uncontrolled PPH in a resource-limited setting. (c) 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Nelson, Brett D.; Stoklosa, Hanni; Ahn, Roy; Eckardt, Melody J.; Walton, Emily K.; Burke, Thomas F.] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA. [Nelson, Brett D.; Stoklosa, Hanni; Ahn, Roy; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Eckardt, Melody J.] Boston Med Ctr, Boston, MA USA. [Walton, Emily K.] Maternal Newborn & Child Survival Initiat, Juba, Sudan. [Burke, Thomas F.] Boston Childrens Hosp, Boston, MA USA. [Burke, Thomas F.] African Inst Innovat & Technol, Kisumu, Kenya. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Zero Emerson Pl, Boston, MA 02114 USA. EM brett.d.nelson@gmail.com OI Eckardt, Melody/0000-0001-9066-9856; Nelson, Brett/0000-0002-5049-1798 FU Department of Emergency Medicine, Massachusetts General Hospital (Boston, MA, USA); PATH (Seattle, WA, USA) FX Funding was provided by the Department of Emergency Medicine, Massachusetts General Hospital (Boston, MA, USA) and PATH (Seattle, WA, USA). NR 17 TC 6 Z9 6 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD JUL PY 2013 VL 122 IS 1 BP 27 EP 32 DI 10.1016/j.ijgo.2013.02.017 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 172BH UT WOS:000320974400007 PM 23623587 ER PT J AU Rogers, DJ Ashland, JE Rozeboom, MJ Hartnick, CJ AF Rogers, Derek J. Ashland, Jean E. Rozeboom, Marie J. Hartnick, Christopher J. TI Modified superior pharyngeal flap for the treatment of velopharyngeal insufficiency in children SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Pharyngeal flap; Velopharyngeal insufficiency; Velopharyngeal dysfunction; Velopharyngeal incompetence ID PHARYNGOPLASTY; SURGERY; PALATE; INSET AB Objective: To describe a modified rolled superior pharyngeal flap for treatment of velopharyngeal insufficiency (VPI) in children. Methods: Prospective case series at a tertiary care multidisciplinary aerodigestive center. Four children, aged 5-12 years, with VPI refractory to speech therapy resulting after cleft palate (bilateral, submucous, or soft palate only) repair, failed traditional superior pharyngeal flap, fine motor incoordination, or adenoidectomy were studied. All 4 children underwent surgery with a modified superior pharyngeal flap, where aspects of the most commonly employed pharyngeal flap designs were combined to achieve the benefits of each technique and to allow for mucosal covering on either side of the flap, improved control of the lateral port size due to the horizontal-to-horizontal inset technique, and the ability to avoid a vertical or horizontal split in a previously repaired cleft palate. Results: All 4 patients demonstrated resolution of their VPI as measured by subjective and/or objective criteria. Every patient required additional speech therapy postoperatively. Conclusions: Our modified superior pharyngeal flap technique may be a good option in patients with small velopharyngeal gaps undergoing revision velopharyngeal surgery. A larger, longitudinal study would better address the overall outcomes of this technique. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Rogers, Derek J.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ashland, Jean E.; Rozeboom, Marie J.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 11 TC 3 Z9 3 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 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2013 VL 77 IS 7 BP 1083 EP 1087 DI 10.1016/j.ijporl.2013.03.035 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 179QB UT WOS:000321535300006 PM 23673163 ER PT J AU Wine, TM Duvvuri, U Maurer, SH Mehta, DK AF Wine, Todd M. Duvvuri, Umamaheswar Maurer, Scott H. Mehta, Deepak K. TI Pediatric transoral robotic surgery for oropharyngeal malignancy: A case report SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Pediatric TORS; Oropharyngeal malignancy; Robot; Head and neck sarcoma; Nonrhabdomyosarcoma ID QUALITY-OF-LIFE; SQUAMOUS-CELL CARCINOMA; LASER MICROSURGERY TLM; SOFT-TISSUE SARCOMAS; PROGNOSTIC-FACTORS; ADJUVANT THERAPY; NECK-CANCER; HEAD; CHEMOTHERAPY; RADIOTHERAPY AB The treatment of oropharyngeal malignancy is associated with numerous functional morbidities. Transoral robotic surgery has been used with increased frequency in adult oropharyngeal malignancy. The benefits include decreased surgical morbidity and improved functional outcomes. Use of transoral robotic has been limited in children. This case represents our experience with a 17-month old child who was diagnosed with a high-grade undifferentiated sarcoma of the soft palate. She was able to be successfully treated with transoral robotic surgery as a part of her multimodal therapy, representing the first case of transoral robotic surgery for an oropharyngeal malignancy in a young child. (c) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Wine, Todd M.; Duvvuri, Umamaheswar; Mehta, Deepak K.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Wine, Todd M.; Mehta, Deepak K.] UPMC, Childrens Hosp Pittsburgh, Div Pediat Otolaryngol, Pittsburgh, PA USA. [Maurer, Scott H.] Univ Pittsburgh, Sch Med, Div Pediat Hematol & Oncol, Pittsburgh, PA 15260 USA. [Duvvuri, Umamaheswar] Vet Affairs Pittsburgh HealthCare Syst, Pittsburgh, PA USA. RP Mehta, DK (reprint author), 4401 Penn Ave Fac Pavil,7th Floor, Pittsburgh, PA 15224 USA. EM Deepak.mehta@chp.edu NR 28 TC 5 Z9 5 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2013 VL 77 IS 7 BP 1222 EP 1226 DI 10.1016/j.ijporl.2013.04.024 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 179QB UT WOS:000321535300036 PM 23680523 ER PT J AU Rosenquist, KJ Pedley, A Massaro, JM Therkelsen, KE Murabito, JM Hoffmann, U Fox, CS AF Rosenquist, Klara J. Pedley, Alison Massaro, Joseph M. Therkelsen, Kate E. Murabito, Joanne M. Hoffmann, Udo Fox, Caroline S. TI Visceral and Subcutaneous Fat Quality and Cardiometabolic Risk SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE computed tomography imaging; epidemiology; obesity; risk factors ID ADIPOSE-TISSUE; INSULIN-RESISTANCE; HUMAN OBESITY; CARDIOVASCULAR-DISEASE; ACID-METABOLISM; BODY-FAT; FRAMINGHAM; HEART; INFLAMMATION; SENSITIVITY AB OBJECTIVES The aim of this study was to evaluate whether computed tomography (CT) attenuation, as a measure of fat quality, is associated with cardiometabolic risk factors above and beyond fat quantity. BACKGROUND Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are pathogenic fat depots associated with cardiometabolic risk. Adipose tissue attenuation in CT images is variable, similar to adipose tissue volume. However, whether the quality of abdominal fat attenuation is associated with cardiometabolic risk independent of the quantity is uncertain. METHODS Participants were drawn from the Framingham Heart Study CT substudy. The VAT and SAT volumes were acquired by semiquantitative assessment. Fat quality was measured by CT attenuation and recorded as mean Hounsfield unit (HU) within each fat depot. Sex-specific linear and logistic multivariable regression models were used to assess the association between standard deviation (SD) decrease in HU and each risk factor. RESULTS Lower CT attenuation of VAT and SAT was correlated with higher body mass index levels in both sexes. Risk factors were generally more adverse with decreasing HU values. For example, in women, per 1 SD decrease in VAT HU, the odds ratio (OR) was increased for hypertension (OR: 1.80), impaired fasting glucose (OR: 2.10), metabolic syndrome (OR: 3.65), and insulin resistance (OR: 3.36; all p < 0.0001). In models that further adjusted for VAT volume, impaired fasting glucose, metabolic syndrome, and insulin resistance remained significant. Trends were similar but less pronounced for SAT and for men. There was evidence of an interaction between HU and fat volume among both women and men. CONCLUSIONS Lower CT attenuation of VAT and SAT is associated with adverse cardiometabolic risk above and beyond total adipose tissue volume. Qualitative indices of abdominal fat depots may provide insight regarding cardiometabolic risk independent of fat quantity. (C) 2013 by the American College of Cardiology Foundation C1 [Rosenquist, Klara J.; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Rosenquist, Klara J.; Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Rosenquist, Klara J.; Pedley, Alison; Therkelsen, Kate E.; Murabito, Joanne M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Rosenquist, Klara J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA 01702 USA. [Rosenquist, Klara J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU NHLBI FHS [N01-HC-25195]; Whitaker Cardiovascular Institute [T32 HL007224] FX This research was conducted in part using data and resources from the Framingham Heart Study (FHS) of the NHLBI of the National Institutes of Health and Boston University School of Medicine. This work was partially supported by NHLBI FHS (N01-HC-25195). Dr. Rosenquist is supported through funding from the Whitaker Cardiovascular Institute (T32 HL007224). Dr. Pedley is an employee of Merck & Co., Inc. All other authors have reported they have no relationships relevant to the contents of this paper to disclose. NR 36 TC 42 Z9 43 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUL PY 2013 VL 6 IS 7 BP 762 EP 771 DI 10.1016/j.jcmg.2012.11.021 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 181OB UT WOS:000321677300003 PM 23664720 ER PT J AU Niemi, SM AF Niemi, Steven M. TI Laboratory animal veterinary medicine responds SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Letter C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Niemi, SM (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JUL 1 PY 2013 VL 243 IS 1 BP 41 EP 42 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 175MX UT WOS:000321235900002 PM 23943934 ER PT J AU Joffe, S AF Joffe, Steven TI RE: Meta-analysis of the Relationship Between Dose and Benefit in Phase I Targeted Agent Trials SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID SURVIVAL C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 7 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUL PY 2013 VL 105 IS 13 BP 993 EP 993 DI 10.1093/jnci/djt125 PG 1 WC Oncology SC Oncology GA 178PR UT WOS:000321460400014 PM 23723419 ER PT J AU Au, TM Dickstein, BD Comer, JS Salters-Pedneault, K Litz, BT AF Au, Teresa M. Dickstein, Benjamin D. Comer, Jonathan S. Salters-Pedneault, Kristalyn Litz, Brett T. TI Co-occurring posttraumatic stress and depression symptoms after sexual assault: A latent profile analysis SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Trauma; Posttraumatic stress disorder; Depression; Comorbidity; Sexual assault; Rape ID CONFIRMATORY FACTOR-ANALYSIS; NATIONAL COMORBIDITY SURVEY; PSYCHOMETRIC PROPERTIES; TRAUMATIC INJURY; RISK-FACTORS; GENERAL-POPULATION; MENTAL-DISORDERS; PRIMARY-CARE; SCALES DASS; DSM-IV AB Background: Symptoms of posttraumatic stress disorder (PTSD) and depression frequently co-occur, but their distinctiveness following trauma remains unclear. We examined patterns of PTSD and depression symptoms after sexual assault to evaluate the extent to which assault survivors primarily reported symptoms of both disorders or whether there were meaningfully distinct subgroups with discordant PTSD and depression symptoms. Methods: Latent profile analysis was used to examine self-reported PTSD and depression symptoms among 119 female sexual assault survivors at 1-, 2-, 3-, and 4-months post-assault. Results: At all time points, a 4-class solution fit the data best, revealing four subgroups with low, low-moderate, high-moderate, and severe levels of both PTSD and depression symptoms. Within each subgroup, PTSD symptom severity co-occurred with comparable depression symptom severity. At no time point were there reliable subgroups with discordant PTSD and depression symptom seventies. Emotional numbing, hyperarousal, and overall PTSD symptom severity reliably distinguished each class from the others. Class membership at 1-month post-assault predicted subsequent class membership and functional impairment. Limitations: Additional research is needed to evaluate predictors of class membership, temporal stability of classes, and generalizability to other trauma populations. Conclusions: Co-occurring and comparably severe PTSD and depression symptoms are pervasive among female sexual assault survivors. The absence of a distinct subset of individuals with only PTSD or depression symptoms suggests that PTSD and depression may be manifestations of a general posttraumatic stress response rather than distinct disorders after trauma. Integrated treatments targeting both PTSD and depression symptoms may therefore prove more efficient and effective. Published by Elsevier B.V. C1 [Au, Teresa M.; Dickstein, Benjamin D.; Comer, Jonathan S.; Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Au, Teresa M.; Dickstein, Benjamin D.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA. [Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT 06226 USA. [Litz, Brett T.] Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Au, TM (reprint author), Boston Univ, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM tau@bu.edu FU Boston Area Rape Crisis Center; VA Career Development Award FX This research was partially funded by the Boston Area Rape Crisis Center and a VA Career Development Award to K Salters-Pedneault. The authors wish to thank Anthony Rosellini for his helpful comments on an earlier version of this work. NR 38 TC 17 Z9 18 U1 4 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2013 VL 149 IS 1-3 BP 209 EP 216 DI 10.1016/j.jad.2013.01.026 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 166XJ UT WOS:000320593000026 PM 23489401 ER PT J AU Wozniak, J Biederman, J Martelon, MK Hernandez, M Woodworth, KY Faraone, SV AF Wozniak, Janet Biederman, Joseph Martelon, Mary Kate Hernandez, Mariely Woodworth, K. Yvonne Faraone, Stephen V. TI Does sex moderate the clinical correlates of pediatric bipolar-I disorder? Results from a large controlled family-genetic study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar; Sex effects; Family study ID DEFICIT HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIALS; SUBSTANCE USE DISORDERS; MANIA; RISK; ONSET; METAANALYSIS; COMORBIDITY; PHENOTYPE; DIAGNOSIS AB Background: Since little is known as to whether sex differences affect the clinical presentation of pediatric BP-I disorder, it is an area of high clinical, scientific and public health relevance. Methods: Subjects are 239 BP-I probands (65 female probands, 174 male probands) and their 726 first-degree relatives, and 136 non-bipolar, non-ADHD control probands (37 female probands, 99 male probands) and their 411 first-degree relatives matched for age and sex. We modeled the psychiatric and cognitive outcomes as a function of BP-I status, sex, and the BP-I status-gender interaction. Results: BP-I disorder was equally familial in both sexes. With the exception of duration of mania (shorter in females) and number of depressive episodes (more in females), there were no other meaningful differences between the sexes in clinical correlates of BP-I disorder. With the exception of a significant sex effect for panic disorder and a trend for substance use disorders (p=0.05) with female probands being at a higher risk than male probands, patterns of comorbidity were similar between the sexes. Despite the similarities, boys with BP-I disorder received more intensive and costly academic services than girls with the same disorder. Limitations: Since we studied children referred to a family study of bipolar disorder, our findings may not generalize to clinic settings. Conclusions: We found more similarities than differences between the sexes in the personal and familial correlates of BP-I disorder. Clinicians should consider bipolar disorder in the differential diagnosis of both boys and girls afflicted with symptoms suggestive of this disorder. (C) 2013 Elsevier B.V. All rights reserved. C1 [Wozniak, Janet; Biederman, Joseph; Martelon, Mary Kate; Hernandez, Mariely; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02140 USA. [Wozniak, Janet; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 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, Clin & Res Programs Pediat Psychopharmacol & Adul, 55 Fruit St,YAW 6A, Boston, MA 02140 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIH [K08MH001503, R01MH066237, R01MH050657, R01HD036317]; Heinz C. Prechter Bipolar Research Fund; Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder FX This work was supported by the NIH Grants K08MH001503 and R01MH066237 to Dr. Wozniak and R01MH050657 and R01HD036317 to Dr. Biederman. This work was also supported by a Grant from the Heinz C. Prechter Bipolar Research Fund, the support of members of the MGH Pediatric Psychopharmacology Council, and the Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder. NR 24 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2013 VL 149 IS 1-3 BP 269 EP 276 DI 10.1016/j.jad.2013.01.040 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 166XJ UT WOS:000320593000035 PM 23485112 ER PT J AU Corson, K Denneson, LM Bair, MJ Helmer, DA Goulet, JL Dobscha, SK AF Corson, Kathryn Denneson, Lauren M. Bair, Matthew J. Helmer, Drew A. Goulet, Joseph L. Dobscha, Steven K. TI Prevalence and correlates of suicidal ideation among Operation Enduring Freedom and Operation Iraqi Freedom veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Suicidal ideation; Depression; Veterans; Primary health care; Mental health; Screening ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH PROBLEMS; POLYTRAUMA CLINICAL TRIAD; RISK-FACTORS; COMBAT VETERANS; FOLLOW-UP; AFFAIRS; CARE; AFGHANISTAN AB Background: We sought to determine the prevalence and correlates of suicidal ideation (SI) among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans following the Department of Veterans Affairs' (VA) 2007 implementation of required brief SI assessments for veterans who screen positive for depression and post-traumatic stress disorder. Methods: We retrospectively identified OEF/OIF veterans screened for depression using the Patient Health Questionnaire (PHQ-2) between April 2008 and September 2009 at three geographically-distinct VA Medical Centers' primary care or mental health clinics. Veteran responses to a two-item risk assessment tool (VA Pocket Card) or PHQ-9 9th item, administered following a positive depression screen (PHQ-2 > 3), were determined using manual chart review. Generalized estimating equations were used to calculate adjusted odds ratios for demographic and clinical correlates of positive SI assessments. Results: Of 1340 OEF/OIF veterans with positive depression screens, 32.4% reported SI. In multivariate models, odds of SI were lower for non-Hispanic white veterans (AOR=0.68) and greater for those with PHQ-2 >= 5 (AOR=1.87), depression (AOR=1.45), bipolar disorder/schizophrenia (AOR=2.84), and 2 or >= 3 diagnoses (AORs=1.59 and 2.49, respectively). Limitations: Study findings may not be generalizable to non-veteran patient populations and the study does not address the reliability and validity of tools employed for brief suicidal ideation assessment. Conclusions: SI is common among OEF/OIF veterans who receive VA care, perhaps more so among non-white veterans. Targeting veterans with higher PHQ-2 scores for SI assessment should be considered to reduce patient and administrative burden. Published by Elsevier B.V. C1 [Corson, Kathryn; Denneson, Lauren M.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Dept Psychiat, Portland, OR 97207 USA. [Bair, Matthew J.] Indiana Univ, Dept Med, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. [Helmer, Drew A.] Univ Med & Dent New Jersey, Sch Med, Vet Affairs New Jersey Hlth Care Syst, War Related Illness & Injury Study Ctr, Newark, NJ USA. [Goulet, Joseph L.] Yale Univ, Sch Med, Dept Psychiat, West Haven Vet Affairs Med Ctr, New Haven, CT USA. [Dobscha, Steven K.] Portland VA Med Ctr, Portland, OR USA. RP Corson, K (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Dept Psychiat, POB 1034 P3 DEP PC, Portland, OR 97207 USA. EM kathryn.corson@va.gov OI Goulet, Joseph/0000-0002-0842-804X FU Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service Project [DHI-08-096] FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service Project DHI-08-096. 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. The funding source had no role in study design; data collection, analysis, or interpretation; or in writing of the manuscript and submission process. NR 71 TC 14 Z9 14 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2013 VL 149 IS 1-3 BP 291 EP 298 DI 10.1016/j.jad.2013.01.043 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 166XJ UT WOS:000320593000038 PM 23531358 ER PT J AU Jabara, HH Ohsumi, T Chou, J Massaad, MJ Benson, H Megarbane, A Chouery, E Mikhael, R Gorka, O Gewies, A Portales, P Nakayama, T Hosokawa, H Revy, P Herrod, H Le Deist, F Lefranc, G Ruland, J Geha, RS AF Jabara, Haifa H. Ohsumi, Toshiro Chou, Janet Massaad, Michel J. Benson, Halli Megarbane, Andre Chouery, Eliane Mikhael, Raymond Gorka, Oliver Gewies, Andreas Portales, Pierre Nakayama, Toshinori Hosokawa, Hiroyuki Revy, Patrick Herrod, Henry Le Deist, Francoise Lefranc, Gerard Ruland, Juergen Geha, Raif S. TI A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE MALT1; combined immunodeficiency (CID); NF-kappa B ID T-CELL; ACTIVATION; IMMUNITY; DEFICIENCY; CARD11 AB Background: Combined immunodeficiency (CID) is characterized by severe recurrent infections with normal numbers of T and B lymphocytes but with deficient cellular and humoral immunity. Most cases are sporadic, but autosomal recessive inheritance has been described. In most cases, the cause of CID remains unknown. Objective: We wanted to identify the genetic cause of CID in 2 siblings, the products of a first-cousin marriage, who experienced recurrent bacterial and candidal infections with bronchiectasis, growth delay, and early death. Methods: We performed immunologic, genetic, and biochemical studies in the 2 siblings, their family members, and healthy controls. Reconstitution studies were performed with T cells from mucosa-associated lymphoid tissue lymphoma-translocation gene 1-deficient (Malt1(-/-)) mice. Results: The numbers of circulating T and B lymphocytes were normal, but T-cell proliferation to antigens and antibody responses to vaccination were severely impaired in both patients. Whole genome sequencing of 1 patient and her parents, followed by DNA sequencing of family members and healthy controls, showed the presence in both patients of a homozygous missense mutation in MALT1 that resulted in loss of protein expression. Analysis of T cells that were available on one of the patients showed severely impaired I kappa B alpha degradation and IL-2 production after activation, 2 events that depend on MALT1. In contrast to wild-type human MALT1, the patients' MALT1 mutant failed to correct defective nuclear factor-kappa B activation and IL-2 production in MALT1-deficient mouse T cells. Conclusions: An autosomal recessive form of CID is associated with homozygous mutations in MALT1. If future patients are found to be similarly affected, they should be considered as candidates for allogeneic hematopoietic cell transplantation. C1 [Jabara, Haifa H.; Chou, Janet; Massaad, Michel J.; Benson, Halli; Geha, Raif S.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Jabara, Haifa H.; Chou, Janet; Massaad, Michel J.; Geha, Raif S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ohsumi, Toshiro] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ohsumi, Toshiro] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Megarbane, Andre; Chouery, Eliane; Lefranc, Gerard] St Joseph Univ, Fac Med, Med Genet Unit, Beirut, Lebanon. [Mikhael, Raymond] St Joseph Univ, Hotel Dieu Hosp, Dept Pediat, Beirut, Lebanon. [Gorka, Oliver; Gewies, Andreas; Ruland, Juergen] Tech Univ Munich, Klinikum Rechts Isar, Inst Klin Chem & Pathobiochem, D-80290 Munich, Germany. [Gewies, Andreas; Ruland, Juergen] German Canc Consortium DKTK, Heidelberg, Germany. [Gewies, Andreas; Ruland, Juergen] German Canc Res Ctr, Heidelberg, Germany. [Portales, Pierre] Ctr Hosp Univ Montpellier, Immunol Lab, Montpellier, France. [Nakayama, Toshinori; Hosokawa, Hiroyuki] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba, Japan. [Revy, Patrick] Univ Paris 05, Inst Imagine, Univ Sorbonne Paris Cite, Paris, France. [Revy, Patrick] INSERM, U768, Paris, France. [Herrod, Henry] Lebonheur Childrens Hosp & Med Ctr, Memphis, TN USA. [Le Deist, Francoise] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. [Lefranc, Gerard] Inst Human Genet, CNRS UPR 1142, Montpellier, France. [Lefranc, Gerard] Univ Montpellier, F-34059 Montpellier, France. [Ruland, Juergen] German Ctr Infect Res DZIF, Braunschweig, Germany. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, 1 Blackfan Circle, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu RI Nakayama, Toshinori/E-1067-2017; OI Gewies, Andreas/0000-0002-7606-6482 FU National Institutes of Health [AI-076210, AI094017]; Deutsche Forschungsgemeinschaft; ERC advanced grant ERC-ADG [LS6]; research council of St Joseph; research council of Chiba Universities; Clinical Immunology/Talecris Fellowship Award; AAAAI/GSK Fellow Career Development Award; National Institutes of Health (NIH); NIH; Japanese government (MEXT); Dubai Harvard Foundation for Medical Research; [5T32AI007512-27]; [K-12 HD052896-01A1] FX Supported by the National Institutes of Health grants AI-076210 and AI094017 (R.S.G.) and grants 5T32AI007512-27 and K-12 HD052896-01A1 (J.C.), a grant from the Dubai Harvard Foundation for Medical Research (R.S.G.), and SFB grants from Deutsche Forschungsgemeinschaft (J.R.), the ERC advanced grant ERC-2012-ADG, LS6 (J.R.), and grants from research councils of St Joseph and Chiba Universities. J.C. has received a Clinical Immunology/Talecris Fellowship Award and an AAAAI/GSK Fellow Career Development Award.; H. H. Jabara, J. Chou, M. J. Massaad, and R. S. Geha have received grants from the National Institutes of Health (NIH). T. Ohsumi has received grants from the NIH, is employed by Seres Health, and has a patent filed through Massachusetts General Hospital. T. Nakayama has received a grant from the Japanese government (MEXT). The rest of the authors declare that they have no relevant conflicts of interest. NR 26 TC 38 Z9 40 U1 1 U2 13 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 JUL PY 2013 VL 132 IS 1 BP 151 EP 158 DI 10.1016/j.jaci.2013.04.047 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 173BF UT WOS:000321052300020 PM 23727036 ER PT J AU Xie, AL Teodorescu, M Pegelow, DF Teodorescu, MC Gong, YS Fedie, JE Dempsey, JA AF Xie, Ailiang Teodorescu, Mihaela Pegelow, David F. Teodorescu, Mihai C. Gong, Yuansheng Fedie, Jessica E. Dempsey, Jerome A. TI Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE isocapnia; hypercapnia; hyperoxia ID CHEYNE-STOKES RESPIRATION; POSITIVE AIRWAY PRESSURE; CONGESTIVE-HEART-FAILURE; TOTAL PULMONARY RESISTANCE; CARBON-DIOXIDE; NREM SLEEP; LOOP GAIN; MECHANICAL VENTILATION; CO2 STIMULATION; MUSCLE-ACTIVITY AB To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predict the success of the treatment aimed at stabilization or increase in respiratory motor outputs, we studied 26 newly diagnosed OSA patients [apnea-hypopnea index (AHI) 42 +/- 5 events/h with 92% of apneas obstructive] who were treated with O-2 supplementation, an isocapnic rebreathing system in which CO2 was added only during hyperpnea to prevent transient hypocapnia, and a continuous rebreathing system. We also measured each patient's controller gain below eupnea [change in minute volume/change in end-tidal PCO2 (Delta(V)over dotE/Delta PETCO2)], CO2 reserve (eupnea-apnea threshold PETCO2), and plant gain (Delta PETCO2 /Delta(V)over dotE), as well as passive upper airway closing pressure (Pcrit). With isocapnic rebreathing, 14/26 reduced their AHI to 31 +/- 6% of control (P < 0.01) (responder); 12/26 did not show significant change (nonresponder). The responders vs. nonresponders had a greater controller gain (6.5 +/- 1.7 vs. 2.1 +/- 0.2 l.min(-1).mmHg(-1), P < 0.01) and a smaller CO2 reserve (1.9 +/- 0.3 vs. 4.3 +/- 0.4 mmHg, P < 0.01) with no differences in Pcrit (-0.1 +/- 1.2 vs. 0.2 +/- 0.9 cmH(2)O, P > 0.05). Hypercapnic rebreathing (+4.2 +/- 1 mmHg PETCO2) reduced AHI to 15 +/- 4% of control (P < 0.001) in 17/21 subjects with a wide range of CO2 reserve. Hyperoxia (SaO(2) similar to 95-98%) reduced AHI to 36 +/- 11% of control in 7/19 OSA patients tested. We concluded that stabilizing central respiratory motor output via prevention of transient hypocapnia prevents most OSA in selected patients with a high chemosensitivity and a collapsible upper airway, whereas increasing respiratory motor output via moderate hypercapnia eliminates OSA in most patients with a wider range of chemosensitivity and CO2 reserve. Reducing chemosensitivity via hyperoxia had a limited and unpredictable effect on OSA. C1 [Xie, Ailiang; Teodorescu, Mihaela; Pegelow, David F.; Teodorescu, Mihai C.; Gong, Yuansheng; Fedie, Jessica E.; Dempsey, Jerome A.] William S Middleton Mem Vet Affairs Hosp, James B Skatrud Lab Pulm & Sleep Med, Madison, WI USA. [Teodorescu, Mihaela] Univ Wisconsin, Dept Med, Madison, WI USA. [Xie, Ailiang; Pegelow, David F.; Fedie, Jessica E.; Dempsey, Jerome A.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Teodorescu, Mihaela; Teodorescu, Mihai C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Xie, AL (reprint author), VA Hosp, James B Skatrud Lab Pulm & Sleep Med, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@wisc.edu FU National Heart, Lung, and Blood Institute [1RC-1-HL-099724-01, HL-15469] FX This work was supported by National Heart, Lung, and Blood Institute Grants 1RC-1-HL-099724-01 and HL-15469. NR 79 TC 17 Z9 18 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2013 VL 115 IS 1 BP 22 EP 33 DI 10.1152/japplphysiol.00064.2013 PG 12 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 174ZW UT WOS:000321199200003 PM 23599393 ER PT J AU Chen, HY Koo, BK Bhatt, DL Kassab, GS AF Chen, Henry Y. Koo, Bon-Kwon Bhatt, Deepak L. Kassab, Ghassan S. TI Impact of stent mis-sizing and mis-positioning on coronary fluid wall shear and intramural stress SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE geographic miss; restenosis; STLLR trial; adverse events; target-vessel revascularization ID DRUG-ELUTING STENTS; ATHEROSCLEROTIC PLAQUES; CLINICAL-OUTCOMES; ENDOTHELIAL SHEAR; RESIDUAL STENOSIS; STLLR TRIAL; FRACTURE; ARTERY; FLOW; INTERVENTION AB Stent deployments with geographical miss (GM) are associated with increased risk of target-vessel revascularization and periprocedural myocardial infarction. The aim of the current study was to investigate the underlying biomechanical mechanisms for adverse events with GM. The hypothesis is that stent deployment with GM [ longitudinal GM, or LGM (i.e., stent not centered on the lesion); or radial GM, RGM (i.e., stent oversizing)] results in unfavorable fluid wall shear stress (WSS), WSS gradient (WSSG), oscillatory shear index (OSI), and intramural circumferential wall stress (CWS). Three-dimensional computational models of stents and plaque were created using a computer-assisted design package. The models were then solved with validated finite element and computational fluid dynamic packages. The dynamic process of large deformation stent deployment was modeled to expand the stent to the desired vessel size. Stent deployed with GM resulted in a 45% increase in vessel CWS compared with stents that were centered and fully covered the lesion. A 20% oversized stent resulted in 72% higher CWS than a correct sized stent. The linkages between the struts had much higher stress than the main struts (i.e., 180 MPa vs. 80 MPa). Additionally, LGM and RGM reduced endothelial WSS and increased WSSG and OSI. The simulations suggest that both LGM and RGM adversely reduce WSS but increase WSSG, OSI, and CWS. These findings highlight the potential mechanical mechanism of the higher adverse events and underscore the importance of stent positioning and sizing for improved clinical outcome. C1 [Chen, Henry Y.; Kassab, Ghassan S.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Koo, Bon-Kwon] Seoul Natl Univ Hosp, Div Cardiol, Seoul 110744, South Korea. [Kassab, Ghassan S.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Chen, Henry Y.; Kassab, Ghassan S.] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Henry Y.; Kassab, Ghassan S.] Indiana Univ Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA. RP Kassab, GS (reprint author), Indiana Univ Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA. EM gkassab@iupui.edu FU National Heart, Lung, and Blood Institute [HL087235, HL084529] FX This research was supported in part by National Heart, Lung, and Blood Institute Grants HL087235 and HL084529. NR 37 TC 4 Z9 4 U1 4 U2 14 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2013 VL 115 IS 2 BP 285 EP 292 DI 10.1152/japplphysiol.00264.2013 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 183MH UT WOS:000321819000018 PM 23722708 ER PT J AU Bouts, MJRJ Tiebosch, IACW van der Toorn, A Viergever, MA Wu, O Dijkhuizen, RM AF Bouts, Mark J. R. J. y Tiebosch, Ivo A. C. W. van der Toorn, Annette Viergever, Max A. Wu, Ona Dijkhuizen, Rick M. TI Early identification of potentially salvageable tissue with MRI-based predictive algorithms after experimental ischemic stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE diffusion-weighted imaging; ischemic stroke; MRI; perfusion imaging; salvageable tissue; tissue outcome prediction ID CEREBRAL-ARTERY OCCLUSION; DIFFUSION; RATS; THROMBOLYSIS; ALTEPLASE; SELECTION; PENUMBRA; INFARCT; FLOW AB Individualized stroke treatment decisions can be improved by accurate identification of the extent of salvageable tissue. Magnetic resonance imaging (MRI)-based approaches, including measurement of a 'perfusion-diffusion mismatch' and calculation of infarction probability, allow assessment of tissue-at-risk; however, the ability to explicitly depict potentially salvageable tissue remains uncertain. In this study, five predictive algorithms (generalized linear model (GLM), generalized additive model, support vector machine, adaptive boosting, and random forest) were tested in their potency to depict acute cerebral ischemic tissue that can recover after reperfusion. Acute T-2-, diffusion-, and perfusion-weighted MRI, and follow-up T-2 maps were collected from rats subjected to right-sided middle cerebral artery occlusion without subsequent reperfusion, for training of algorithms (Group I), and with spontaneous (Group II) or thrombolysis-induced reperfusion (Group III), to determine infarction probability-based viability thresholds and prediction accuracies. The infarction probability difference between irreversible-i.e., infarcted after reperfusion-and salvageable tissue injury-i.e., noninfarcted after reperfusion-was largest for GLM (20 +/- 7%) with highest accuracy of risk-based identification of acutely ischemic tissue that could recover on subsequent reperfusion (Dice's similarity index = 0.79 +/- 0.14). Our study shows that assessment of the heterogeneity of infarction probability with MRI-based algorithms enables estimation of the extent of potentially salvageable tissue after acute ischemic stroke. C1 [Bouts, Mark J. R. J. y; Tiebosch, Ivo A. C. W.; van der Toorn, Annette; Dijkhuizen, Rick M.] Univ Med Ctr Utrecht, Image Sci Inst, NL-3584 CX Utrecht, Netherlands. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Dijkhuizen, RM (reprint author), Univ Med Ctr Utrecht, Image Sci Inst, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM r.m.dijkhuizen@umcutrecht.nl RI Viergever, Max/J-1215-2014; OI Dijkhuizen, Rick/0000-0002-4623-4078 FU Netherlands Heart Foundation [2005B156]; European Union's Seventh Framework Programme (FP7) [201024, 202213] FX The research leading to these results was funded by the Netherlands Heart Foundation (2005B156), and the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements no 201024 and no 202213 (European Stroke Network). NR 41 TC 9 Z9 9 U1 0 U2 6 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 JUL PY 2013 VL 33 IS 7 BP 1075 EP 1082 DI 10.1038/jcbfm.2013.51 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 174VW UT WOS:000321185800013 PM 23571283 ER PT J AU Singh, A Happel, C Manna, SK Acquaah-Mensah, G Carrerero, J Kumar, S Nasipuri, P Krausz, KW Wakabayashi, N Dewi, R Boros, LG Gonzalez, FJ Gabrielson, E Wong, KK Girnun, G Biswal, S AF Singh, Anju Happel, Christine Manna, Soumen K. Acquaah-Mensah, George Carrerero, Julian Kumar, Sarvesh Nasipuri, Poonam Krausz, Kristopher W. Wakabayashi, Nobunao Dewi, Ruby Boros, Laszlo G. Gonzalez, Frank J. Gabrielson, Edward Wong, Kwok K. Girnun, Geoffrey Biswal, Shyam TI Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LUNG-CANCER CELLS; PROSTATE-CANCER; NRF2-REGULATED GENES; MASS ISOTOPOMER; RECEPTOR-ALPHA; PENTOSE CYCLE; NUCLEIC-ACID; TUMOR-GROWTH; HUMAN BREAST; E3 LIGASE AB The mechanisms by which deregulated nuclear factor erythroid-2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and C-13-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, reprogramming glucose metabolism. Sustained activation of NRF2 signaling in cancer cells attenuated miR-1 and miR-206 expression, leading to enhanced expression of PPP genes. Conversely, overexpression of miR-1 and miR-206 decreased the expression of metabolic genes and dramatically impaired NADPH production, ribose synthesis, and in vivo tumor growth in mice. Loss of NRF2 decreased the expression of the redox-sensitive histone deacetylase, HDAC4, resulting in increased expression of miR-1 and miR-206, and not only inhibiting PPP expression and activity but functioning as a regulatory feedback loop that repressed HDAC4 expression. In primary tumor samples, the expression of miR-1 and miR-206 was inversely correlated with PPP gene expression, and increased expression of NRF2-dependent genes was associated with poor prognosis. Our results demonstrate that microRNA-dependent (miRNA-dependent) regulation of the PPP via NRF2 and HDAC4 represents a novel link between miRNA regulation, glucose metabolism, and ROS homeostasis in cancer cells. C1 [Singh, Anju; Happel, Christine; Kumar, Sarvesh; Nasipuri, Poonam; Biswal, Shyam] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Manna, Soumen K.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Acquaah-Mensah, George] Massachusetts Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Worcester, MA USA. [Carrerero, Julian; Wong, Kwok K.] Univ Valencia, Dept Physiol, Valencia, Spain. [Wakabayashi, Nobunao] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Dewi, Ruby; Girnun, Geoffrey] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Boros, Laszlo G.] SIDMAP LLC, Los Angeles, CA USA. [Boros, Laszlo G.] Harbor UCLA Med Ctr, Dept Pediat, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Gabrielson, Edward; Biswal, Shyam] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD 21205 USA. [Wong, Kwok K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Biswal, S (reprint author), Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, E7624,615 North St, Baltimore, MD 21205 USA. EM asingh1@jhsph.edu; ggirnun@som.umaryland.edu; sbiswal@jhsph.edu RI Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; Acquaah-Mensah, George/0000-0003-3984-8327 FU NIH [RO1 CA140492]; National Cancer Institute SPORE [P50 CA058184, P30ES03819, P30CA006973]; Maryland Cigarette Restitution Fund; National Research Service Award from the National Cancer Institute [NRSA-F32]; Flight Attendant Medical Research Institute; National Cancer Institute [122794, 166480, 163896, 140594, 141576]; Young Clinical Innovator Award FX This work was supported by NIH grant RO1 CA140492 (to S. Biswal); National Cancer Institute SPORE grants P50 CA058184 (to S. Biswal), P30ES03819, and P30CA006973; a research grant from the Maryland Cigarette Restitution Fund (to S. Biswal and G. Girnun); a National Research Service Award (NRSA-F32) from the National Cancer Institute (to C. Happel); a Young Clinical Innovator Award (to S. Biswal); and a Young Clinical Scientist Award (to A. Singh) from the Flight Attendant Medical Research Institute. K.K. Wong is supported by National Cancer Institute grants 122794, 166480, 163896,140594, and 141576. NR 57 TC 78 Z9 81 U1 1 U2 31 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2013 VL 123 IS 7 BP 2921 EP 2934 DI 10.1172/JCI66353 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 176PN UT WOS:000321316700020 PM 23921124 ER PT J AU Bilton, D Bellon, G Charlton, B Cooper, P De Boeck, K Flume, PA Fox, HG Gallagher, CG Geller, DE Haarman, EG Hebestreit, HU Kolbe, J Lapey, A Robinson, P Wu, J Zuckerman, JB Aitken, ML AF Bilton, Diana Bellon, Gabriel Charlton, Brett Cooper, Peter De Boeck, Kris Flume, Patrick A. Fox, Howard G. Gallagher, Charles G. Geller, David E. Haarman, Eric G. Hebestreit, Helge U. Kolbe, John Lapey, Allen Robinson, Phil Wu, Jian Zuckerman, Jonathan B. Aitken, Moira L. CA CF301 Investigators CF302 Investigators TI Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE Cystic fibrosis; Mannitol dry powder; FEV1; Airway mucociliary clearance; Clinical study; Dry powder inhalers ID DRY-POWDER MANNITOL; PULMONARY-FUNCTION; MUCOCILIARY CLEARANCE; MUCUS CLEARANCE; LUNG-FUNCTION; BRONCHIECTASIS; EXACERBATIONS; INHALATION; SPUTUM AB Background: To evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population. Methods: Data were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks. Results: Both the mean absolute change in FEV1 (mL) and relative change in FEV1 by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p<0.001). Increases in FEV1 were observed irrespective of rhDNase use. Significant improvements in FEV1 occurred in adults but not children (6-11) or adolescents (aged 12-17). Pulmonary exacerbation incidence was reduced by 29% (p=0.039) in the mannitol (400 mg) group. Conclusions: Sustained six-month improvements in lung function and decreased pulmonary exacerbation incidence indicate that inhaled mannitol is an important additional drug in the treatment of CF. (c) 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. C1 [Bilton, Diana] Royal Brompton Hosp, London SW3 6LY, England. [Bellon, Gabriel] Univ Lyon 1, F-69622 Villeurbanne, France. [Charlton, Brett; Fox, Howard G.; Wu, Jian] Pharmaxis Ltd, Frenchs Forest, Sydney, NSW, Australia. [Cooper, Peter] Childrens Hosp, Sydney, NSW, Australia. [De Boeck, Kris] Univ Hosp Leuven, Louvain, Belgium. [Flume, Patrick A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Gallagher, Charles G.] St Vincents Univ Hosp, Dublin 4, Ireland. [Geller, David E.] Florida State Univ, Coll Med, Orlando, FL USA. [Haarman, Eric G.] Univ Amsterdam, Acad Med Ctr, Dept Pediat Pulmonol, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Haarman, Eric G.] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Pulmonol, Amsterdam, Netherlands. [Hebestreit, Helge U.] Univ Kinderklin Wurzberg, Wurzburg, Germany. [Kolbe, John] Univ Auckland, Auckland 1, New Zealand. [Lapey, Allen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Robinson, Phil] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Robinson, Phil] Univ Melbourne, Royal Childrens Hosp Melbourne, Melbourne, Vic 3010, Australia. [Zuckerman, Jonathan B.] Maine Med Ctr, Portland, ME 04102 USA. [Aitken, Moira L.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Bilton, D (reprint author), Royal Brompton Hosp, London SW3 6LY, England. EM d.bilton@rbht.nhs.uk FU NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust; Imperial College London; Cystic Fibrosis Foundation (CFF); Therapeutic Development Network (TDN); Pharmaxiss Limited FX This work was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London and the Cystic Fibrosis Foundation (CFF) and Therapeutic Development Network (TDN).; Pharmaxiss Limited. NR 30 TC 24 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 EI 1873-5010 J9 J CYST FIBROS JI J. Cyst. Fibros PD JUL PY 2013 VL 12 IS 4 BP 367 EP 376 DI 10.1016/j.jcf.2012.11.002 PG 10 WC Respiratory System SC Respiratory System GA 173OM UT WOS:000321088800008 PM 23234802 ER PT J AU Bot, AGJ Becker, SJE Mol, MF Ring, D Vranceanu, AM AF Bot, Arjan G. J. Becker, Stephanie J. E. Mol, Marianne F. Ring, David Vranceanu, Ana-Maria TI Validation of Phone Administration of Short-Form Disability and Psychology Questionnaires SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Abbreviated measures; depression; disability; health anxiety; pain catastrophizing ID FOLLOW-UP; TELEPHONE INTERVIEWS; PATIENT SATISFACTION; ARM PAIN; DEPRESSION; VALIDITY; NONRESPONSE; QUICKDASH; SYMPTOMS; SHOULDER AB Purpose To assess whether there was a difference in score between paper and telephone administration of disability and psychological questionnaires relevant to patients with an upper extremity illness. Methods The short version of the Disabilities of the Arm, Shoulder, and Hand score, the 5-question version of the Short Health Anxiety Inventory, the 4-question version of the Pain Catastrophizing Scale, the Patient Health Questionnaire-2, and an ordinal pain scale were completed by 135 patients both in the office and the next day over the phone. We compared scores with repeated measures analysis of variance and Pearson correlation. We used intraclass correlation coefficients to test the level of agreement. Results There were small but significant differences between paper and phone administration of the short version of the Disabilities of the Arm, Shoulder, and Hand scores and pain scores, but not the Patient Health Questionnaire-2, Short Health Anxiety Inventory-5, and Pain Catastrophizing Scale-4. There was a large Pearson correlation and excellent intraclass correlation coefficient agreement, as well. Conclusions Shorter questionnaires can be used to assess disability and psychological factors by phone. Phone administration of measures of disability and psychological factors can replace paper administration in studies that do not require in-person examination. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Behav Med,Benson Henry Mind Body Inst, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 NR 28 TC 6 Z9 6 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2013 VL 38A IS 7 BP 1383 EP 1387 DI 10.1016/j.jhsa.2013.03.033 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 174NB UT WOS:000321161600015 PM 23707596 ER PT J AU Liu, CY Krishnan, AP Yan, LR Smith, RX Kilroy, E Alger, JR Ringman, JM Wang, DJJ AF Liu, Collin Y. Krishnan, Anitha P. Yan, Lirong Smith, Robert X. Kilroy, Emily Alger, Jeffery R. Ringman, John M. Wang, Danny J. J. TI Complexity and synchronicity of resting state blood oxygenation level-dependent (BOLD) functional MRI in normal aging and cognitive decline SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE resting state BOLD fMRI; approximate entropy (ApEn); complexity; aging; familial Alzheimer's disease (fAD); default mode network (DMN) ID APPROXIMATE ENTROPY; ALZHEIMERS-DISEASE; BRAIN ACTIVITY; FRACTAL DYNAMICS; FMRI; FREQUENCY; CLINICIAN; HORMONE; NETWORK; SYSTEM AB Purpose: To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in normal aging and cognitive decline associated with familial Alzheimer's disease (fAD). Materials and Methods: Resting state BOLD fMRI data were acquired at 3T from two independent cohorts of subjects consisting of healthy young (age 23 +/- 2 years, n = 8) and aged volunteers (age 66 +/- 3 years, n = 8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2 +/- 15.8 years; and eight nonmutation carrying family members, age 28.8 +/- 5.9 years). Mean ApEn values were compared between the two age groups and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain. Results: Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis. Conclusion: ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neuro-degenerative diseases. C1 [Liu, Collin Y.; Yan, Lirong; Smith, Robert X.; Kilroy, Emily; Alger, Jeffery R.; Ringman, John M.; Wang, Danny J. J.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Liu, Collin Y.] Greater Los Angeles Vet Adm Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. [Liu, Collin Y.; Krishnan, Anitha P.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Liu, Collin Y.] Univ So Calif, Dept Radiol, Los Angeles, CA USA. [Ringman, John M.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. RP Wang, DJJ (reprint author), Univ Calif Los Angeles, Dept Neurol, 660 Charles E Young Dr South, Los Angeles, CA 90095 USA. EM jwang71@gmail.com FU National Institutes of Health (NIH) [R01-MH080892, P50-AG016570, U01-AG032438]; Easton Consortium for Alzheimer's Disease Drug and Biomarker Discovery FX Contract grant sponsor: National Institutes of Health (NIH); Contract grant numbers: R01-MH080892, P50-AG016570, U01-AG032438, Easton Consortium for Alzheimer's Disease Drug and Biomarker Discovery. NR 40 TC 17 Z9 17 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUL PY 2013 VL 38 IS 1 BP 36 EP 45 DI 10.1002/jmri.23961 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 180SA UT WOS:000321614600005 PM 23225622 ER PT J AU Ersek, M Smith, D Cannuscio, C Richardson, DM Moore, D AF Ersek, Mary Smith, Dawn Cannuscio, Carolyn Richardson, Diane M. Moore, Denise TI A Nationwide Study Comparing End-of-Life Care for Men and Women Veterans SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY IMPROVEMENT; GENDER-DIFFERENCES; FAMILY ASSESSMENT; PALLIATIVE CARE; AFFAIRS; PERCEPTIONS; CANCER; PAIN AB Background: The quality of end-of-life (EOL) care at Veterans Affairs Medical Centers (VAMC) has improved. To date, however, the quality and outcomes of end-of-life care delivered to women veterans have not been examined. Objective: The goal of this study was to evaluate gender differences in the quality of EOL care received by patients in VAMCs nationwide. Design: The study was conducted via retrospective medical chart review and telephone survey with next of kin of recently deceased inpatients. Setting/subjects: The chart review included records for all patients who died in acute and long-term care units in 145 VAMCs nationwide (n = 36,618). For the survey, the documented next of kin were invited to respond on behalf of the deceased veteran; a total of 25,638 next of kin completed the survey. Measurements: Chart review measures included five indicators of optimal end-of-life care. Bereaved family survey items included one global and nine specific items (e. g., bereavement care, pain management) describing care in the last month of life. Results: Receipt of optimal end-of-life care did not differ significantly between women and men with respect to frequency of discussion of treatment goals with a family member, receipt of palliative consult, bereavement contact, and chaplain contact with a family member. Family members of women were more likely than those of men to report that the overall care provided to the veteran had been "excellent" (adjusted proportions: 63% versus 56%; odds ratio (OR) = 1.33; 95% confidence interval (CI) 1.10-1.61; p = 0.003). Conclusions: In this nationwide study of all inpatient deaths in VAMCs, women received comparable and on some metrics better quality EOL care than that received by male patients. C1 [Ersek, Mary; Smith, Dawn; Richardson, Diane M.; Moore, Denise] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, PROMISE Ctr, Philadelphia, PA 19104 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. RP Ersek, M (reprint author), Philadelphia VAMC, PROMISE Ctr, 3900 Woodland Ave,ANNEX Bldg, Philadelphia, PA 19104 USA. EM ersekm@nursing.upenn.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. 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 Stated Government. The authors thank Melissa Dichter, MSW, PhD, for her thoughtful review of the manuscript prior to its submission. NR 31 TC 8 Z9 8 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL PY 2013 VL 16 IS 7 BP 734 EP 740 DI 10.1089/jpm.2012.0537 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 169GV UT WOS:000320768900009 PM 23676096 ER PT J AU Yonekawa, Y VanderVeen, DK Shah, AS AF Yonekawa, Yoshihiro VanderVeen, Deborah K. Shah, Ankoor S. TI Congenital Glaucoma SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Yonekawa, Yoshihiro; VanderVeen, Deborah K.; Shah, Ankoor S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Boston Childrens Hosp, Boston, MA 02115 USA. RP Yonekawa, Y (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Boston Childrens Hosp, Boston, MA 02115 USA. NR 3 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 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2013 VL 163 IS 1 BP 301 EP 301 DI 10.1016/j.jpeds.2013.01.067 PG 1 WC Pediatrics SC Pediatrics GA 179BZ UT WOS:000321494000066 PM 23498156 ER PT J AU Lonergan, MH Olivera-Figueroa, LA Pitman, RK Brunet, A AF Lonergan, Michelle H. Olivera-Figueroa, Lening A. Pitman, Roger K. Brunet, Alain TI Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Review ID BETA-ADRENERGIC-BLOCKADE; POSTTRAUMATIC-STRESS-DISORDER; NORADRENERGIC MODULATION; PROTEIN-SYNTHESIS; YOUNG MEN; RETRIEVAL; TRAUMA; FEAR; REACTIVATION; AMYGDALA AB Background: Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the beta-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults. Methods: Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model. Results: Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00). Limitations: Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results. Conclusion: Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations, such as patients with posttraumatic stress or other event-related disorders. C1 [Lonergan, Michelle H.; Brunet, Alain] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Lonergan, Michelle H.; Brunet, Alain] Douglas Mental Hlth Univ Inst, Montreal, PQ H4H 1R3, Canada. [Olivera-Figueroa, Lening A.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Olivera-Figueroa, Lening A.] US Dept Vet Affairs, West Haven, CT 06516 USA. [Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. RP Brunet, A (reprint author), Douglas Mental Hlth Univ Inst, 6875 Blvd LaSalle, Montreal, PQ H4H 1R3, Canada. EM alain.brunet@mcgill.ca OI Olivera-Figueroa, Lening/0000-0001-6325-9819 FU Fonds de Recherche du Quebec - Sante; Canadian Institutes of Health Research; Fernand-Seguin Research Centre FX A. Brunet holds a salary award from the Fonds de Recherche du Quebec - Sante. M. H. Lonergan holds a student award from the Canadian Institutes of Health Research. L. A. Olivera-Figueroa holds a postdoctoral fellowship from the Fernand-Seguin Research Centre. NR 60 TC 40 Z9 41 U1 1 U2 37 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD JUL PY 2013 VL 38 IS 4 BP 222 EP 231 DI 10.1503/jpn.120111 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 180CR UT WOS:000321571000007 PM 23182304 ER PT J AU Cooper, RA AF Cooper, Rory A. TI Technology, trends, and the future for people with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Editorial Material C1 [Cooper, Rory A.] Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA 15260 USA. [Cooper, Rory A.] US Dept Vet Affairs, Philadelphia, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2013 VL 36 IS 4 BP 257 EP 257 DI 10.1179/1079026813Z.000000000197 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 180DU UT WOS:000321574200001 PM 23820141 ER PT J AU Collinger, JL Foldes, S Bruns, TM Wodlinger, B Gaunt, R Weber, DJ AF Collinger, Jennifer L. Foldes, Stephen Bruns, Tim M. Wodlinger, Brian Gaunt, Robert Weber, Douglas J. TI Neuroprosthetic technology for individuals with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Review DE Spinal cord injuries; Assistive technology; Neural interface; Neuroprosthesis; Brain-computer interface; Electrical stimulation; Epidural stimulation; Central pattern generators; Neurogenic bladder; Paraplegia; Tetraplegia; Rehabilitation ID FUNCTIONAL ELECTRICAL-STIMULATION; SILICON MICROELECTRODE ARRAYS; PUDENDAL NERVE-STIMULATION; BRAIN-COMPUTER INTERFACES; INTRASPINAL MICROSTIMULATION; INTRACORTICAL MICROSTIMULATION; NEUROMUSCULAR STIMULATION; BLADDER CONTRACTIONS; MICRO STIMULATION; SACRAL NEUROMODULATION AB Context: Spinal cord injury (SCI) results in a loss of function and sensation below the level of the lesion. Neuroprosthetic technology has been developed to help restore motor and autonomic functions as well as to provide sensory feedback. Findings: This paper provides an overview of neuroprosthetic technology that aims to address the priorities for functional restoration as defined by individuals with SCI. We describe neuroprostheses that are in various stages of preclinical development, clinical testing, and commercialization including functional electrical stimulators, epidural and intraspinal microstimulation, bladder neuroprosthesis, and cortical stimulation for restoring sensation. We also discuss neural recording technologies that may provide command or feedback signals for neuroprosthetic devices. Conclusion/clinical relevance: Neuroprostheses have begun to address the priorities of individuals with SCI, although there remains room for improvement. In addition to continued technological improvements, closing the loop between the technology and the user may help provide intuitive device control with high levels of performance. C1 [Collinger, Jennifer L.; Foldes, Stephen; Weber, Douglas J.] Dept Vet Affairs, Pittsburgh, PA USA. [Collinger, Jennifer L.; Foldes, Stephen; Bruns, Tim M.; Wodlinger, Brian; Gaunt, Robert; Weber, Douglas J.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Collinger, Jennifer L.; Gaunt, Robert; Weber, Douglas J.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Foldes, Stephen; Wodlinger, Brian; Weber, Douglas J.] Ctr Neural Basis Cognit, Pittsburgh, PA USA. RP Collinger, JL (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM collingr@pitt.edu OI Gaunt, Robert/0000-0001-6202-5818; Bruns, Tim/0000-0003-1692-0541 FU Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs [B6789C, B7143R, RX720]; Defense Advanced Research Projects Agency (DARPA) [N66001-10-C-4056]; National Institutes of Health, National Institute of Neurological Disorders and Stroke [F32NS074565]; UPMC Rehabilitation Institute FX This material is based on work supported by the Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs (Grants #B6789C, B7143R, and RX720), the Defense Advanced Research Projects Agency (DARPA) Revolutionizing Prosthetics program contract number N66001-10-C-4056, the National Institutes of Health, National Institute of Neurological Disorders and Stroke Grant #F32NS074565, and the UPMC Rehabilitation Institute. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of Veterans Affairs, Department of Defense, National Institutes of Health, National Institute of Neurological Disorders and Stroke, or the United States government. NR 178 TC 15 Z9 17 U1 2 U2 42 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2013 VL 36 IS 4 BP 258 EP 272 DI 10.1179/2045772313Y.0000000128 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 180DU UT WOS:000321574200002 PM 23820142 ER PT J AU Fineberg, DB Asselin, P Harel, NY Agranova-Breyter, I Kornfeld, SD Bauman, WA Spungen, AM AF Fineberg, Drew B. Asselin, Pierre Harel, Noam Y. Agranova-Breyter, Irina Kornfeld, Stephen D. Bauman, William A. Spungen, Ann M. TI Vertical ground reaction force-based analysis of powered exoskeleton-assisted walking in persons with motor-complete paraplegia SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injury; Paraplegia; Rehabilitation; ReWalk (TM); Assistive technology; Robotic-assisted exoskeletal device; Vertical ground reaction force; Mechanical loading; F-scan (TM) tekscan; Fourier series ID SPINAL-CORD-INJURY; RECIPROCATING GAIT ORTHOSIS AB Objective: To use vertical ground reaction force (vGRF) to show the magnitude and pattern of mechanical loading in persons with spinal cord injury (SCI) during powered exoskeleton-assisted walking. Research design: A cross-sectional study was performed to analyze vGRF during powered exoskeleton-assisted walking (ReWalk (TM): Argo Medical Technologies, Inc, Marlborough, MA, USA) compared with vGRF of able-bodied gait. Setting: Veterans Affairs Medical Center. Participants: Six persons with thoracic motor-complete SCI (T1-T11 AIS A/B) and three age-, height-, weight- and gender-matched able-bodied volunteers participated. Interventions: SCI participants were trained to ambulate over ground using a ReWalk (TM). vGRF was recorded using the F-Scan (TM) system (TekScan, Boston, MA, USA). Outcome measures: Peak stance average (PSA) was computed from vGRF and normalized across all participants by percent body weight. Peak vGRF was determined for heel strike, mid-stance, and toe-off. Relative linear impulse and harmonic analysis provided quantitative support for analysis of powered exoskeletal gait. Results: Participants with motor-complete SCI, ambulating independently with a ReWalk (TM), demonstrated mechanical loading magnitudes and patterns similar to able-bodied gait. Harmonic analysis of PSA profile by Fourier transform contrasted frequency of stance phase gait components between able-bodied and powered exoskeleton-assisted walking. Conclusion: Powered exoskeleton-assisted walking in persons with motor-complete SCI generated vGRF similar in magnitude and pattern to that of able-bodied walking. This suggests the potential for powered exoskeleton-assisted walking to provide a mechanism for mechanical loading to the lower extremities. vGRF profile can be used to examine both magnitude of loading and gait mechanics of powered exoskeleton-assisted walking among participants of different weight, gait speed, and level of assist. C1 [Fineberg, Drew B.; Asselin, Pierre; Harel, Noam Y.; Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, VA Rehabil Res & Dev, Bronx, NY USA. [Harel, Noam Y.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Harel, Noam Y.; Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Agranova-Breyter, Irina] James J Peters VA Med Ctr, Rehabil Med Serv, Bronx, NY USA. [Kornfeld, Stephen D.] James J Peters VA Med Ctr, Spinal Cord Injury Serv, Bronx, NY USA. [Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Med Serv, Bronx, NY USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Spungen, AM (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ann.spungen@va.gov FU Rehabilitation Medicine Service, Spinal Cord Injury Service, Prosthetics and Orthotics Service James J. Peters Veterans Affairs Medical Center, Department of Neurology; Mount Sinai School of Medicine; Department of Veterans Affairs Rehabilitation Research and Development Service [B9212-C] FX We thank our participants and volunteers for their hard work and commitment. This work was supported by the Rehabilitation Medicine Service, Spinal Cord Injury Service, Prosthetics and Orthotics Service James J. Peters Veterans Affairs Medical Center, Department of Neurology, Mount Sinai School of Medicine, and the Department of Veterans Affairs Rehabilitation Research and Development Service (B9212-C). We would like to acknowledge Argo Medical Technologies, Inc. for loaning two ReWalk units and Aetrex Worldwide, Inc. for donating orthopedic shoes for this project. NR 15 TC 27 Z9 27 U1 5 U2 40 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2013 VL 36 IS 4 BP 313 EP 321 DI 10.1179/2045772313Y.0000000126 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 180DU UT WOS:000321574200007 PM 23820147 ER PT J AU Mahajan, HP Dicianno, BE Cooper, RA Ding, D AF Mahajan, Harshal P. Dicianno, Brad E. Cooper, Rory A. Ding, Dan TI Assessment of wheelchair driving performance in a virtual reality-based simulator SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Wheelchair; Assistive technology; Virtual reality; Driving simulator; User-computer interface; Multiple sclerosis; Cerebral palsy; Muscular dystrophy; Spinal cord injury ID TRAUMATIC BRAIN-INJURY; POWERED WHEELCHAIR; JOYSTICK; REHABILITATION; ENVIRONMENTS; ENHANCEMENT; RELIABILITY; EXPERIENCE; VALIDITY; MOBILITY AB Objective: To develop a virtual reality (VR)-based simulator that can assist clinicians in performing standardized wheelchair driving assessments. Design: A completely within-subjects repeated measures design. Methods: Participants drove their wheelchairs along a virtual driving circuit modeled after the Power Mobility Road Test (PMRT) and in a hallway with decreasing width. The virtual simulator was displayed on computer screen and VR screens and participants interacted with it using a set of instrumented rollers and a wheelchair joystick. Driving performances of participants were estimated and compared using quantitative metrics from the simulator. Qualitative ratings from two experienced clinicians were used to estimate intra- and inter-rater reliability. Results: Ten regular wheelchair users (seven men, three women; mean age +/- SD, 39.5 +/- 15.39 years) participated. The virtual PMRT scores from the two clinicians show high inter-rater reliability (78-90%) and high intra-rater reliability (71-90%) for all test conditions. More research is required to explore user preferences and effectiveness of the two control methods (rollers and mathematical model) and the display screens. Conclusions: The virtual driving simulator seems to be a promising tool for wheelchair driving assessment that clinicians can use to supplement their real-world evaluations. C1 [Mahajan, Harshal P.; Dicianno, Brad E.; Cooper, Rory A.; Ding, Dan] VA Pittsburgh HealthCare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. [Mahajan, Harshal P.; Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Dicianno, Brad E.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Dicianno, BE (reprint author), VA Pittsburgh HealthCare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM dicianno@pitt.edu FU Department of Veteran Affairs Research and Development Merit Review Award [A6035R] FX This study is supported by the Department of Veteran Affairs Research and Development Merit Review Award (Grant #A6035R) and with resources and facilities by the Human Engineering Research Laboratories, VA Pittsburgh HealthCare System. The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. NR 47 TC 4 Z9 4 U1 2 U2 17 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2013 VL 36 IS 4 BP 322 EP 332 DI 10.1179/2045772313Y.0000000130 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 180DU UT WOS:000321574200008 PM 23820148 ER PT J AU Garcia-Mendez, Y Pearlman, JL Boninger, ML Cooper, RA AF Garcia-Mendez, Yasmin Pearlman, Jonathan L. Boninger, Michael L. Cooper, Rory A. TI Health risks of vibration exposure to wheelchair users in the community SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Wheelchair; Manual; Vibration exposure; Wheelchair design; Paraplegia; Tetraplegia; Low back pain; Spinal disorders; Wheelchair sports; Veterans ID WHOLE-BODY VIBRATION; LOW-BACK-PAIN; MANUAL WHEELCHAIRS; SEAT CUSHIONS; SIDEWALK SURFACES; SUSPENSION; PROPULSION; INDIVIDUALS; SUPPORTS AB Objective: The purpose of this study was to evaluate whole-body vibration (WBV) exposure to wheelchair (WC) users in their communities and to determine the effect of WC frame type (folding, rigid, and suspension) in reducing WBV transmitted to the person. Design: An observational case-control study of the WBV exposure levels among WC users. Participants: Thirty-seven WC users, with no pressure sores, 18 years old or older and able to perform independent transfers. Main outcome measures: WC users were monitored for 2 weeks to collect WBV exposure, as well as activity levels, by using custom vibration and activity data-loggers. Vibration levels were evaluated using ISO 2631-1 methods. Results: All WC users who participated in this study were continuously exposed to WBV levels at the seat that were within and above the health caution zone specified by ISO 2631-1 during their day-to-day activities (0.83 +/- 0.17 m/second(2), weighted root-mean-squared acceleration, for 13.07 +/- 3.85 hours duration of exposure). WCs with suspension did not attenuate vibration transmitted to WC users (V = 0.180, F(8, 56) = 0.692, P = 0.697). Conclusions: WBV exposure to WC users exceeds international standards. Suspension systems need to be improved to reduce vibrations transmitted to the users. C1 [Garcia-Mendez, Yasmin; Pearlman, Jonathan L.; Boninger, Michael L.; Cooper, Rory A.] VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. [Garcia-Mendez, Yasmin; Pearlman, Jonathan L.; Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Boninger, Michael L.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Pearlman, Jonathan L.; Boninger, Michael L.; Cooper, Rory A.] Ctr Excellence WCs & Related Technol, VA Rehabil Res & Dev Serv, Pittsburgh, PA USA. [Garcia-Mendez, Yasmin] Univ Autonoma Estado Mexico, Fac Med, Dept Phys Therapy, Mexico City, DF, Mexico. RP Pearlman, JL (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, 6425 Penn Ave Suite 400, Pittsburgh, PA 15206 USA. EM jlp46@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136; Boninger, Michael/0000-0001-6966-919X FU Veterans Affairs Healthcare Network: VISN 4 Competitive Pilot Project [02778, B6673M]; Associated Rehabilitation Engineering (WaRE) VA center of excellence [B6789C]; Mexican Foundation for Education, Technology and Science (FUNED) [120701793-8]; Mexican National Council of Science and Technology (CONACyT) [212007] FX This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Healthcare Network: VISN 4 Competitive Pilot Project Fund #02778, Career Development Award grant #B6673M, WC and Associated Rehabilitation Engineering (WaRE) VA center of excellence grant #B6789C, the Mexican Foundation for Education, Technology and Science (FUNED) scholarship register #120701793-8, and the Mexican National Council of Science and Technology (CONACyT) scholarship register #212007. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. Thanks are extended to the Human Engineering Research Labs shop staff, clinical coordinators, students, and participants. NR 29 TC 2 Z9 2 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUL PY 2013 VL 36 IS 4 BP 365 EP 375 DI 10.1179/2045772313Y.0000000124 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 180DU UT WOS:000321574200012 PM 23820152 ER PT J AU Hollis, BW Marshall, DT Savage, SJ Garrett-Mayer, E Kindy, MS Gattoni-Celli, S AF Hollis, Bruce W. Marshall, David T. Savage, Stephen J. Garrett-Mayer, Elizabeth Kindy, Mark S. Gattoni-Celli, Sebastiano TI Vitamin D-3 supplementation, low-risk prostate cancer, and health disparities SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 15th Vitamin D Workshop CY JUN 20-22, 2012 CL Houston, TX DE Vitamin D; Prostate cancer; Biopsy; Health disparities ID 1,25-DIHYDROXYVITAMIN D-3; CONSERVATIVE MANAGEMENT; AFRICAN-AMERICAN; WHITE MEN; GROWTH; CELLS; IDENTIFICATION; EXPRESSION; GENE; PREVALENCE AB Vitamin D promotes the differentiation of prostate cancer cells, raising the possibility that vitamin D deficiency over time may contribute to the progression from subclinical prostate cancer to clinical disease. Since low-risk prostate cancers are monitored over time in an effort to determine which progress into clinically important, more aggressive cancers, they provide an excellent model in which to study, over an extended period of time, the effects of enhancing vitamin D status and related changes in tumor progression. This is particularly relevant to African-American men, who exhibit a high prevalence of vitamin D deficiency as well as higher incidence of prostate cancer and higher mortality rates from prostate cancer than Caucasians. Our research team has recently completed an open-label clinical trial aimed at assessing the safety and potential efficacy of vitamin D-3 supplementation at 4000 international units (IU) per day for one year in subjects diagnosed with early stage, low-risk prostate cancer. The results of this clinical study suggest that supplementation with vitamin D-3 at 4000 IU per day may benefit patients with early stage, low-risk prostate cancer on active surveillance, because of the improved outcome (a decreased number of positive cores at repeat biopsy) in more than half of the subjects enrolled in the trial. We also observed that, after one year of supplementation, there was no difference in circulating levels of vitamin D between African-American and Caucasian subjects who completed the study. These clinical results also suggest that robust and sustained vitamin D-3 supplementation can reduce prostate cancer-related health disparities in African-American men and that these health disparities are at least in part the result of widespread hypovitaminosis D within the African-American population. This article is part of a Special Issue entitled 'Vitamin D Workshop'. C1 [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Marshall, David T.; Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Savage, Stephen J.] Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Dept Med Biostat, Charleston, SC 29425 USA. [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Savage, Stephen J.; Kindy, Mark S.; Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Gattoni-Celli, S (reprint author), Strom Thurmond Biomed Res Bldg,Room 338C,114 Doug, Charleston, SC 29403 USA. EM gattonis@musc.edu FU Gateway for Cancer Research; Health Services Research and Development Program of the Department of Veterans Affairs; South Carolina Clinical and Translational Research Institute,; Biostatistics Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313] FX These studies were supported in part by grants from the Gateway for Cancer Research, the Health Services Research and Development Program of the Department of Veterans Affairs, the South Carolina Clinical and Translational Research Institute, and the Biostatistics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313). The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. We thank Drs. Leander Cannick, Jason Zauls, Kyle Russo, and Lewis Cooper (MUSC Department of Radiation Oncology) for helping with the recruitment of eligible subjects. NR 45 TC 9 Z9 9 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUL PY 2013 VL 136 SI SI BP 233 EP 237 DI 10.1016/j.jsbmb.2012.11.012 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 177WJ UT WOS:000321405800049 PM 23220550 ER PT J AU Bikle, DD Elalieh, H Welsh, J Oh, D Cleaver, J Teichert, A AF Bikle, Daniel D. Elalieh, Hashem Welsh, JoEllen Oh, Dennis Cleaver, James Teichert, Arnaud TI Protective role of vitamin D signaling in skin cancer formation SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 15th Vitamin D Workshop CY JUN 20-22, 2012 CL Houston, TX DE Vitamin D receptor; 1,25-Dihydroxyvitamin D; Keratinocyte; UVR; DNA damage repair; Sonic hedgehog ID BASAL-CELL CARCINOMA; TRANSCRIPTION-COUPLED REPAIR; PRIMARY HUMAN KERATINOCYTES; TUMOR-SUPPRESSOR GENE; D-RECEPTOR; DNA-REPAIR; EXCISION-REPAIR; SONIC HEDGEHOG; ULTRAVIOLET-RADIATION; INDUCED TUMORIGENESIS AB Vitamin D sufficiency is associated with protection against malignancy in a number of tissues clinically, and a strong body of evidence from animal and cell culture studies supports this protective role. Cancers in the skin differ, however, in that higher serum levels of 25OHD are associated with increased basal cell carcinomas (BCC), the most common form of epidermal malignancy. This result may be interpreted as indicating the role of UVR (spectrum 280-320) in producing vitamin D in the skin as well as causing those DNA mutations and proliferative changes that lead to epidermal malignancies. Recent animal studies have shown that mice lacking the vitamin D receptor (VDR) are predisposed to developing skin tumors either from chemical carcinogens such as 7,12-dimethylbenzanthracene (DMBA) or chronic UVR exposure. Such studies suggest that vitamin D production and subsequent signaling through the VDR in the skin may have evolved in part as a protective mechanism against UVR induced epidermal cancer formation. In this manuscript we provide evidence indicating that vitamin D signaling protects the skin from cancer formation by controlling keratinocyte proliferation and differentiation, facilitating DNA repair, and suppressing activation of the hedgehog (Hh) pathway following UVR exposure. This article is part of a Special Issue entitled 'Vitamin D Workshop'. Published by Elsevier Ltd. C1 [Bikle, Daniel D.; Elalieh, Hashem; Teichert, Arnaud] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Bikle, Daniel D.; Elalieh, Hashem; Oh, Dennis; Cleaver, James; Teichert, Arnaud] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Welsh, JoEllen] SUNY Albany, GenNYsis Ctr Excellence Canc Genom, Rensselaer, NY USA. [Bikle, Daniel D.; Oh, Dennis; Cleaver, James] San Francisco VA Med Ctr, Dept Dermatol, San Francisco, CA USA. RP Bikle, DD (reprint author), San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. EM daniel.bikle@ucsf.edu FU NIH [RO1 AR050023, DOD CA110338]; VA Merit Reviews; University of California Cancer Coordinating Committee grants FX The authors acknowledge the administrative support of Teresa Tong and Victoria Lee, the technical support of Sally Pennypacker, Stephanie Demetriou, and Katherine Ona-Vu, and the funding support from NIH RO1 AR050023 (DDB), DOD CA110338 (DDB), VA Merit Reviews (DDB and DHO), and the University of California Cancer Coordinating Committee grants (DHO, JEC). NR 68 TC 15 Z9 16 U1 0 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUL PY 2013 VL 136 SI SI BP 271 EP 279 DI 10.1016/j.jsbmb.2012.09.021 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 177WJ UT WOS:000321405800055 PM 23059470 ER PT J AU Potter, JS Marino, EN Hillhouse, MP Nielsen, S Wiest, K Canamar, CP Martin, JA Ang, A Baker, R Saxon, AJ Ling, W AF Potter, Jennifer S. Marino, Elise N. Hillhouse, Maureen P. Nielsen, Suzanne Wiest, Katharina Canamar, Catherine P. Martin, Judith A. Ang, Alfonso Baker, Rachael Saxon, Andrew J. Ling, Walter TI Buprenorphine/Naloxone and Methadone Maintenance Treatment Outcomes for Opioid Analgesic, Heroin, and Combined Users: Findings From Starting Treatment With Agonist Replacement Therapies (START) SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; INJECTION-DRUG USERS; SPECIFICATION TESTS; RANDOMIZED-TRIAL; DEPENDENCE; TRANSITION; HEALTH AB Objective: The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use. Method: A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition. Results: Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition. Conclusions: Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users. C1 [Potter, Jennifer S.; Marino, Elise N.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hillhouse, Maureen P.; Ang, Alfonso; Ling, Walter] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA. [Nielsen, Suzanne] Univ Sydney, Discipline Addict Med, Sydney, NSW 2006, Australia. [Wiest, Katharina; Baker, Rachael] CODA Inc, Portland, OR USA. [Canamar, Catherine P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, Judith A.] City & Cty San Francisco, Dept Publ Hlth, Community Behav Hlth Serv, San Francisco, CA USA. [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Potter, JS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7526 Louis Pasteur,MC7733, San Antonio, TX 78229 USA. EM PotterJS@uthscsa.edu RI Nielsen, Suzanne/C-3256-2015; Potter, Jennifer/C-6720-2008 OI Nielsen, Suzanne/0000-0001-5341-1055; Potter, Jennifer/0000-0002-7250-4422 FU National Institute on Drug Abuse Clinical Trials Network [U10 DA020024, U10 DA13045, 5 U10 DA013714-08, U10 DA13036, K23 DA02297] FX This research was supported by National Institute on Drug Abuse Clinical Trials Network Grants U10 DA020024 (to Madhukar H. Trivedi), U10 DA13045 (to Walter Ling), 5 U10 DA013714-08 (to Dennis Donovan), U10 DA13036 (to Dennis McCarty), and K23 DA02297 (to Jennifer S. Potter). NR 27 TC 32 Z9 32 U1 4 U2 18 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD JUL PY 2013 VL 74 IS 4 BP 605 EP 613 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 175LC UT WOS:000321231200013 PM 23739025 ER PT J AU Mckay, JR Van Horn, D Ivey, M Drapkin, ML Rennert, L Lynch, KG AF McKay, James R. Van Horn, Deborah Ivey, Megan Drapkin, Michelle L. Rennert, Lior Lynch, Kevin G. TI Enhanced Continuing Care Provided in Parallel to Intensive Outpatient Treatment Does Not Improve Outcomes for Patients With Cocaine Dependence SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID RECOVERY MANAGEMENT CHECKUPS; ADDICTION SEVERITY INDEX; SUBSTANCE-ABUSE PATIENTS; DRINKING BEHAVIOR; 24-MONTH OUTCOMES; USE DISORDERS; SELF-REPORTS; ALCOHOL; RELIABILITY; VALIDITY AB Objective: This study tested whether the addition of an enhanced continuing care (ECC) intervention that combined in-person and telephone sessions and began in the first week of treatment improved outcomes for cocaine-dependent patients entering an intensive outpatient program (IOP). Method: Participants (N = 152) were randomized to IOP treatment as usual (TAU) or IOP plus 12 months of ECC. ECC included cognitive-behavioral therapy elements to increase coping skills, as well as monetary incentives for attendance. It was provided by counselors situated at a separate clinical research facility who did not provide IOP. The primary outcomes measured were (a) cocaine urine toxicology and (b) good clinical outcome, as indicated by abstinence from all drugs and from heavy alcohol use. Secondary outcomes were frequency of abstinent days, cocaine use days, and heavy drinking days. Follow-ups were conducted at 3, 6, 9, and 12 months after baseline. Results: Patients in ECC completed a mean of 18 sessions. Contrary to the hypotheses, patients in TAU had better scores on both the cocaine urine toxicology and the good clinical outcome measures than those in ECC, as indicated by significant Group x Time interactions (cocaine urine toxicology, p=.0025; abstinence composite, p=.017). These results were not moderated by substance use before or early in treatment or by IOP attendance. Results with the secondary outcomes also did not favor ECC over TAU. Conclusions: Continuing care that is not well integrated with the primary treatment program may interfere in some way with the therapeutic process, particularly when it is implemented shortly after intake. C1 [McKay, James R.; Van Horn, Deborah; Ivey, Megan; Drapkin, Michelle L.; Rennert, Lior; Lynch, Kevin G.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [McKay, James R.; Drapkin, Michelle L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Mckay, JR (reprint author), Univ Penn, Ctr Continuum Care Addict, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM Mckay_j@mail.trc.upenn.edu FU National Institute on Drug Abuse [RC1 DA029062, K24 DA029062]; Medical Research Service; Substance Use Disorder Quality Enhancement Research Initiative (SUD-QUERI) of the Department of Veterans Affairs FX This research was supported by National Institute on Drug Abuse Grants RC1 DA029062 and K24 DA029062. Additional support was provided by the Medical Research Service and the Substance Use Disorder Quality Enhancement Research Initiative (SUD-QUERI) of the Department of Veterans Affairs. NR 32 TC 4 Z9 4 U1 1 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD JUL PY 2013 VL 74 IS 4 BP 642 EP 651 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 175LC UT WOS:000321231200018 PM 23739030 ER PT J AU Dodgion, CM Neville, BA Lipsitz, SR Hu, YY Schrag, D Breen, E Greenberg, CC AF Dodgion, Christopher M. Neville, Bridget A. Lipsitz, Stuart R. Hu, Yue-Yung Schrag, Deborah Breen, Elizabeth Greenberg, Caprice C. TI Do older Americans undergo stoma reversal following low anterior resection for rectal cancer? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 04-08, 2010 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) DE Stoma reversal; Low anterior resection; Rectal cancer; Elderly patients ID TOTAL MESORECTAL EXCISION; TEMPORARY LOOP ILEOSTOMY; QUALITY-OF-LIFE; DEFUNCTIONING STOMA; COMORBIDITY INDEX; MULTICENTER TRIAL; MORBIDITY; MORTALITY; SURGERY; METAANALYSIS AB Objective: For low-lying rectal cancers, proximal diversion can reduce anastomotic leak after sphincter-preserving surgery; however, evidence suggests that such temporary diversions are often not reversed. We aimed to evaluate nonreversal and delayed stoma reversal in elderly patients undergoing low anterior resection (LAR). Design: SEER-Medicare-linked analysis from 1991-2007. Settings and participants: A total of 1179 primary stage I-III rectal cancer patients over age 66 who underwent LAR with synchronous diverting stoma. Main outcome measures: (1) Stoma creation and reversal rates; (2) time to reversal; (3) characteristics associated with reversal and shorter time to reversal. Results: Within 18 mo of LAR, 51% of patients (603/1179) underwent stoma reversal. Stoma reversal was associated with age <80 y (P < 0.0001), male sex (P = 0.018), fewer comorbidities (P = 0.017), higher income (quartile 4 versus 1; P = 0.002), early tumor stage (1 versus 3; P < 0.001), neoadjuvant radiation (P < 0.0001), rectal tumor location (versus rectosigmoid; P = 0.001), more recent diagnosis (P = 0.021), and shorter length of stay on LAR admission (P = 0.021). Median time to reversal was 126 d (interquartile range: 79-249). Longer time to reversal was associated with older age (P = 0.031), presence of comorbidities (P = 0.014), more advanced tumor stage (P = 0.007), positive lymph nodes (P = 0.009), receipt of adjuvant radiation therapy (P = 0.008), more recent diagnosis (P = 0.004), and longer length of stay on LAR admission (P < 0.0001). Conclusions: Half of elderly rectal cancer patients who undergo LAR with temporary stoma have not undergone stoma reversal by 18 mo. Identifiable risk factors predict both nonreversal and longer time to reversal. These results help inform preoperative discussions and promote realistic expectations for elderly rectal cancer patients. (C) 2013 Elsevier Inc. All rights reserved. C1 [Dodgion, Christopher M.; Greenberg, Caprice C.] Univ Wisconsin Hosp & Clin, Wisconsin Surg Outcomes Res Program, Dept Surg, Madison, WI 53792 USA. [Neville, Bridget A.; Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. [Lipsitz, Stuart R.; Hu, Yue-Yung; Breen, Elizabeth] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Greenberg, CC (reprint author), Univ Wisconsin Hosp & Clin, Wisconsin Surg Outcomes Res Program, Dept Surg, 600 Highland Ave,BX7375 Clinical Sci Ctr, Madison, WI 53792 USA. EM greenberg@surgery.wisc.edu RI Dodgion, Chris/A-2877-2016 OI Dodgion, Chris/0000-0002-5789-7731 FU NCI NIH HHS [T32 CA009535, T32-CA009535-23] NR 39 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2013 VL 183 IS 1 BP 238 EP 245 DI 10.1016/j.jss.2012.11.057 PG 8 WC Surgery SC Surgery GA 166ZK UT WOS:000320599600037 PM 23298948 ER PT J AU Maemura, T Shin, M Kinoshita, M AF Maemura, Tomoyuki Shin, Michael Kinoshita, Manabu TI Tissue engineering of the stomach SO JOURNAL OF SURGICAL RESEARCH LA English DT Review DE Tissue engineering; Postgastrectomy syndrome; Stomach reconstruction; Gastric wall patch transplantation ID EARLY GASTRIC-CANCER; ENDOSCOPIC SUBMUCOSAL DISSECTION; OPEN DISTAL GASTRECTOMY; QUALITY-OF-LIFE; JEJUNAL POUCH RECONSTRUCTION; RANDOMIZED CONTROLLED-TRIAL; ROUX-EN-Y; POSTGASTRECTOMY SYNDROMES; SEGMENTAL GASTRECTOMY; MUCOSAL CELLS AB Tissue engineering combines engineering principles with the biological sciences to create functional replacement tissues. The underlying principle of tissue engineering is that isolated cells combined with biomaterials can form new tissues and organs in vitro and in vivo. This review focuses on stomach tissue engineering, which is a promising approach to the treatment of gastric cancer, the fourth most common malignancy in the world and the second-leading cause of cancer mortality worldwide. Although gastrectomy is a reliable intervention to achieve complete removal of cancer lesions, the limited capacity for food intake after resection results in lower quality of life for patients. To address this issue, we have developed a tissue-engineered stomach to increase the capacity for food intake by creating a new food reservoir. We have transplanted this neo-stomach as a substitute for the original native stomach in a rat model and confirmed functional adaptation. Furthermore, we have demonstrated the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Although progress has been achieved, significant challenges remain to bring this approach to clinical practice. Here, we summarize our work and present the state of the art in stomach tissue engineering. (C) 2013 Elsevier Inc. All rights reserved. C1 [Maemura, Tomoyuki] Natl Def Med Coll, Div Traumatol, Res Inst, Tokorozawa, Saitama 3598513, Japan. [Maemura, Tomoyuki] Natl Def Med Coll, Dept Surg, Tokorozawa, Saitama 3598513, Japan. [Shin, Michael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shin, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Kinoshita, Manabu] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama 3598513, Japan. RP Maemura, T (reprint author), Natl Def Med Coll, Div Basic Traumatol, Res Inst, Namiki 3-2, Tokorozawa, Saitama 3598513, Japan. EM maemura@ndmc.ac.jp NR 84 TC 5 Z9 5 U1 1 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2013 VL 183 IS 1 BP 285 EP 295 DI 10.1016/j.jss.2013.02.032 PG 11 WC Surgery SC Surgery GA 166ZK UT WOS:000320599600043 PM 23622729 ER PT J AU Theriault, RL Carlson, RW Allred, C Anderson, BO Burstein, HJ Edge, SB Farrar, WB Forero, A Giordano, SH Goldstein, LJ Gradishar, WJ Hayes, DF Hudis, CA Isakoff, SJ Ljung, BME Mankoff, DA Marcom, PK Mayer, IA McCormick, B Pierce, LJ Reed, EC Schwartzberg, LS Smith, ML Soliman, H Somlo, G Ward, JH Wolff, AC Zellars, R Shead, DA Kumar, R AF Theriault, Richard L. Carlson, Robert W. Allred, Craig Anderson, Benjamin O. Burstein, Harold J. Edge, Stephen B. Farrar, William B. Forero, Andres Giordano, Sharon Hermes Goldstein, Lori J. Gradishar, William J. Hayes, Daniel F. Hudis, Clifford A. Isakoff, Steven J. Ljung, Britt-Marie E. Mankoff, David A. Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Pierce, Lori J. Reed, Elizabeth C. Schwartzberg, Lee S. Smith, Mary Lou Soliman, Hatem Somlo, George Ward, John H. Wolff, Antonio C. Zellars, Richard Shead, Dorothy A. Kumar, Rashmi TI Breast Cancer, Version 3.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID TRASTUZUMAB PLUS DOCETAXEL; PERTUZUMAB; TRIAL; TOLERABILITY; N9831 AB These NCCN Guidelines Insights highlight the important updates specific to the management of HER2-positive metastatic breast cancer in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. These include new first-line and subsequent therapy options for patients with HER2-positive metastatic breast cancer. C1 [Theriault, Richard L.; Giordano, Sharon Hermes] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Carlson, Robert W.] Stanford Canc Inst, Stanford, CA USA. [Allred, Craig] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Anderson, Benjamin O.; Mankoff, David A.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Farrar, William B.] Solove Res Inst, Columbus, OH USA. [Forero, Andres] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Goldstein, Lori J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hayes, Daniel F.; Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hudis, Clifford A.; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Reed, Elizabeth C.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Lincoln, NE USA. [Schwartzberg, Lee S.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Soliman, Hatem] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Theriault, RL (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. FU NCI NIH HHS [P30 CA006973] NR 19 TC 83 Z9 91 U1 1 U2 10 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUL PY 2013 VL 11 IS 7 BP 753 EP 761 PG 9 WC Oncology SC Oncology GA 180RY UT WOS:000321614400003 PM 23847214 ER PT J AU Greenberg, PL Attar, E Bennett, JM Bloomfield, CD Borate, U De Castro, CM Deeg, HJ Frankfurt, O Gaensler, K Garcia-Manero, G Gore, SD Head, D Komrokji, R Maness, LJ Millenson, M O'Donnell, MR Shami, PJ Stein, BL Stone, RM Thompson, JE Westervelt, P Wheeler, B Shead, DA Naganuma, M AF Greenberg, Peter L. Attar, Eyal Bennett, John M. Bloomfield, Clara D. Borate, Uma De Castro, Carlos M. Deeg, H. Joachim Frankfurt, Olga Gaensler, Karin Garcia-Manero, Guillermo Gore, Steven D. Head, David Komrokji, Rami Maness, Lori J. Millenson, Michael O'Donnell, Margaret R. Shami, Paul J. Stein, Brady L. Stone, Richard M. Thompson, James E. Westervelt, Peter Wheeler, Benton Shead, Dorothy A. Naganuma, Maoko TI Myelodysplastic Syndromes SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; QUALITY-OF-LIFE; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ACUTE MYELOGENOUS LEUKEMIA; PROGNOSTIC SCORING SYSTEM; WORLD-HEALTH-ORGANIZATION; CHRONIC MYELOPROLIFERATIVE DISORDERS AB The myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic disorders characterized by cytopenias, dysplasia in one or more myeloid lineages, and the potential for development of acute myeloid leukemia. These disorders primarily affect older adults. The NCCN Clinical Practice Guidelines in Oncology for MDS provide recommendations on the diagnostic evaluation and classification of MDS, risk evaluation according to established prognostic assessment tools (including the new revised International Prognostic Scoring System), treatment options according to risk categories, and management of related anemia. C1 [Greenberg, Peter L.] Stanford Canc Inst, Stanford, CA USA. [Attar, Eyal] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bennett, John M.; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Inst Res, Columbus, OH 43210 USA. [Borate, Uma] Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA. [Frankfurt, Olga] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gore, Steven D.] Sidney Kimmel Comprehens Canc Ctr, Sidney, BC, Canada. [Head, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Maness, Lori J.] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Stein, Brady L.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Thompson, James E.] Roswell Pk Canc Inst, Buffalo, NY USA. [Westervelt, Peter] Washington Univ, Sch Med, Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63130 USA. [Wheeler, Benton] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Greenberg, PL (reprint author), Stanford Canc Inst, Stanford, CA USA. FU NCI NIH HHS [K24 CA111717, P30 CA016672] NR 182 TC 42 Z9 43 U1 0 U2 6 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 JUL PY 2013 VL 11 IS 7 BP 838 EP 874 PG 37 WC Oncology SC Oncology GA 180RY UT WOS:000321614400009 PM 23847220 ER PT J AU Bekelman, JE Suneja, G Guzzo, T Pollack, CE Armstrong, K Epstein, AJ AF Bekelman, Justin E. Suneja, Gita Guzzo, Thomas Pollack, Craig Evan Armstrong, Katrina Epstein, Andrew J. TI Effect of Practice Integration Between Urologists and Radiation Oncologists on Prostate Cancer Treatment Patterns SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; physician's practice patterns; radiotherapy, intensity-modulated; delivery of health care, integrated ID THERAPY; COST; CARE; TECHNOLOGIES; RADIOTHERAPY AB Purpose: National attention has focused on whether urology-radiation oncology practice integration, known as integrated prostate cancer centers, contributes to the use of intensity modulated radiation therapy, a common and expensive prostate cancer treatment. Materials and Methods: We examined prostate cancer treatment patterns before and after conversion of a urology practice to an integrated prostate cancer center in July 2006. Using the SEER (Statistics, Epidemiology and End Results)-Medicare database, we identified patients 65 years old or older in 1 statewide registry diagnosed with nonmetastatic prostate cancer between 2004 and 2007. We classified patients into 3 groups, including 1-those seen by integrated prostate cancer center physicians (exposure group), 2-those living in the same hospital referral region who were not seen by integrated prostate cancer center physicians (hospital referral region control group) and 3-those living elsewhere in the state (state control group). We compared changes in treatment among the 3 groups, adjusting for patient, clinical and socioeconomic factors. Results: Compared with the 8.1 ppt increase in adjusted intensity modulated radiation therapy use in the state control group, the use of this therapy increased 20.3 ppts (95% CI 13.4, 27.1) in the integrated prostate cancer center group and 19.2 ppts (95% CI 9.6, 28.9) in the hospital referral region control group. Androgen deprivation therapy, for which Medicare reimbursement decreased sharply, similarly decreased in integrated prostate cancer center and hospital referral region controls. Prostatectomy decreased significantly in the integrated prostate cancer center group. Conclusions: Coincident with the conversion of a urology group practice to an integrated prostate cancer center, we observed an increase in intensity modulated radiation therapy and a decrease in androgen deprivation therapy in patients seen by integrated prostate cancer center physicians and those seen in the surrounding health care market that were not observed in the remainder of the state. C1 [Bekelman, Justin E.; Suneja, Gita] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Guzzo, Thomas] Univ Penn, Perelman Sch Med, Dept Surg, Div Urol, Philadelphia, PA 19104 USA. [Armstrong, Katrina; Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Guzzo, Thomas; Armstrong, Katrina; Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Pollack, Craig Evan; Armstrong, Katrina; Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Pollack, Craig Evan] Johns Hopkins Sch Med, Dept Gen Internal Med, Baltimore, MD USA. RP Bekelman, JE (reprint author), Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Radiat Oncol, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU National Cancer Institute [K07-CA163616] FX Supported by National Cancer Institute K07-CA163616 (JEB). NR 25 TC 16 Z9 16 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 JUL PY 2013 VL 190 IS 1 BP 97 EP 101 DI 10.1016/j.juro.2013.01.103 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 178GH UT WOS:000321432900027 PM 23399652 ER PT J AU Foss, FM Sjak-Shie, N Goy, A Jacobsen, E Advani, R Smith, MR Komrokji, R Pendergrass, K Bolejack, V AF Foss, Francine M. Sjak-Shie, Nelida Goy, Andre Jacobsen, Eric Advani, Ranjana Smith, Mitchell R. Komrokji, Rami Pendergrass, Kelly Bolejack, Vanessa TI A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study SO LEUKEMIA & LYMPHOMA LA English DT Article DE Denileukin diftitox; CHOP; lymphoma; T-cell; phase II; clinical trial; fusion protein toxin ID NON-HODGKIN-LYMPHOMA; CHOP CHEMOTHERAPY AB This phase II study to determine the safety and efficacy of denileukin diftitox (DD) and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) enrolled patients with newly diagnosed peripheral T-cell lymphoma (PTCL). Forty-nine received DD 18 mu g/kg/day (days 1, 2) with CHOP (day 3) every 21 days for <= 6-8 cycles. Intent-to-treat (ITT) and safety populations comprised all patients. In the ITT population, the overall response rate was 65%, median duration of response was 30 months and median progression-free survival was 12 months. Median overall survival was not attained at the end of the study, and the overall survival rate was 63.3%. The two most frequent treatment-related adverse events (AEs) were fatigue and nausea. Most frequent AEs >= grade 3 within the hematologic system were lymphopenia (24.5%), neutropenia (20.4%) and leukopenia (18.4%). Three treatment-related deaths occurred. DD plus CHOP was well tolerated, and progression-free and overall survival improved versus historical comparison with CHOP alone. Confirmation in larger trials is warranted. C1 [Foss, Francine M.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. [Sjak-Shie, Nelida] Womens Oncol Ctr, St Louis, MO USA. [Goy, Andre] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Jacobsen, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Advani, Ranjana] Stanford Univ, Stanford, CA 94305 USA. [Smith, Mitchell R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Komrokji, Rami] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Pendergrass, Kelly] Kansas City Canc Ctr, Kansas City, MO USA. [Bolejack, Vanessa] Canc Res & Biostat, Seattle, WA USA. RP Foss, FM (reprint author), Yale Canc Ctr, Dept Med Oncol, 333 Cedar St FMP 130,POB 208032, New Haven, CT 06520 USA. EM francine.foss@yale.edu OI Smith, Mitchell/0000-0003-1428-8765 FU Eisai Inc. FX This study was sponsored by Eisai Inc. Editorial support for this manuscript was provided by Sui Generis Health and by Peloton Advantage, LLC, and was funded by Eisai Inc. We thank Kara Nyberg, PhD, of Sui Generis Health for providing medical writing and editorial assistance, and Yvonne E. Yarker, PhD, CMPP, of Peloton Advantage, LLC, for providing editorial support. NR 18 TC 22 Z9 24 U1 0 U2 9 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 JUL PY 2013 VL 54 IS 7 BP 1373 EP 1379 DI 10.3109/10428194.2012.742521 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 168IE UT WOS:000320698300009 PM 23278639 ER PT J AU Poghosyan, H Sheldon, LK Leveille, SG Cooley, ME AF Poghosyan, Hermine Sheldon, Lisa Kennedy Leveille, Suzanne G. Cooley, Mary E. TI Health-related queality of life after surgical treatment in patients with non-small cell lung cancer: A systematic review SO LUNG CANCER LA English DT Review DE Literature review; Non-small cell lung cancer; Surgery; Health-related quality of life; Symptoms; Smoking cessation ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; CLINICAL-TRIALS; THORACIC-SURGERY; SMOKING-CESSATION; EARLY-STAGE; THORACOTOMY; RESECTION; PNEUMONECTOMY; COMPLICATIONS AB Introduction: Surgical resection currently is the best available treatment to enhance long-term survival after non-small cell lung cancer (NSCLC). With the anticipated growth in the number of NSCLC survivors diagnosed through computed tomography screening, health-related quality of life (HR-QOL) as an endpoint of treatment will become increasingly important. This article is a systematic review of the literature regarding HR-QOL in patients after surgical treatment. Methods: Three computerized databases (PubMed, Medline, and CINHAL) were used to identify relevant articles. Inclusion criteria were: empirical studies English language, assessment of HR-QOL after surgical treatment for stage I, II, or III NSCLC, and publication prior to January 2012. Data were abstracted and content analyses were used to synthesize the findings. Results: Nineteen out of 337 studies were reviewed. The majority of participants (67%) had stable or improved mental HR-QOL at 6-months after surgery. Compared with the general population, however, NSCLC survivors have poorer mental HR-QOL. Compared to pre-surgical status, participants had worse physical function at 6-months after surgery and had decreased physical function up to 2-years after surgery. Pain, fatigue, dyspnea and coughing were the most prevalent symptoms. Increased levels of dyspnea and fatigue persisted for at least 2-years after surgery. Continued smoking, presence of comorbidities, extensive surgical resection, and use of adjuvant therapy were associated with lower HR-QOL. Conclusions: New interventions focused on smoking cessation, improving symptom control and physical function are needed to enhance HR-QOL after lung cancer surgery. Published by Elsevier Ireland Ltd. C1 [Poghosyan, Hermine] Univ Calif Davis, Betty Irene Moore Sch Nursing, Sacramento, CA 95817 USA. [Sheldon, Lisa Kennedy; Leveille, Suzanne G.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Res Nursing Serv, Boston, MA 02115 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Patient Care Serv, Boston, MA 02115 USA. RP Poghosyan, H (reprint author), Educ Bldg,4610 X St,Suite 4202, Sacramento, CA 95817 USA. EM hermine.poghosyan@ucdmc.ucdavis.edu NR 47 TC 28 Z9 28 U1 0 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2013 VL 81 IS 1 BP 11 EP 26 DI 10.1016/j.lungcan.2013.03.013 PG 16 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 174TQ UT WOS:000321178700002 PM 23562675 ER PT J AU Hoang, T Dahlberg, SE Schiller, JH Johnson, DH AF Hoang, Tien Dahlberg, Suzanne E. Schiller, Joan H. Johnson, David H. TI Does histology predict survival of advanced non-small cell lung cancer patients treated with platin-based chemotherapy? An analysis of the Eastern Cooperative Oncology Group Study E1594 SO LUNG CANCER LA English DT Article DE NSCLC; Histology; Prognostic; Survival; First-line chemotherapy ID VINORELBINE PLUS CISPLATIN; PHASE-III TRIAL; THYMIDYLATE SYNTHASE; DOCETAXEL; REGIMENS AB Introduction: We conducted this analysis to determine whether survival of advanced NSCLC patients treated with platin-based chemotherapy doublets involving paclitaxel, docetaxel or gemcitabine was dependent on histological subtypes and treatment regimen. Methods: We retrospectively analyzed data from El 594, a front-line phase III study in which advanced NSCLC patients were randomized to receive one of four regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, and carboplatin-paclitaxel. Patients were classified into four histology groups: squamous cell (SCC), adeno- (AC), large cell (LCC) and others including not otherwise specified (0/NOS) carcinoma. Logrank test was performed to compare overall survival (OS) and progression free survival (PFS) distributions according to histology as well as treatment. Results: Of 1139 patients including 716 men and 423 women, AC was the most common subtype (56.8%), followed by SCC (19.7%), O/NOS (17.0%) and LCC (6.5%). Men were more likely to have SCC and women were more likely to have AC (p = 0.002). Among the four histology groups, there was no imbalance in regard to race, performance status, weight loss, brain metastasis or treatment. In each histology group, we found no significant difference in OS and PFS between the four chemotherapy regimens. Conversely, in each treatment arm, the survival outcome was similar between the four histology subtypes. Conclusions: Our analysis suggests that histology does not predict survival benefit in advanced NSCLC patients treated with first-line platin-based doublets involving paclitaxel, docetaxel or gemcitabine. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Hoang, Tien] Univ Wisconsin, Wisconsin Inst Med Res, Hematol Oncol Sect, Madison, WI 53705 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schiller, Joan H.; Johnson, David H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Hoang, T (reprint author), Univ Wisconsin, Wisconsin Inst Med Res, Hematol Oncol Sect, 1111 Highland Ave,Room 3131, Madison, WI 53705 USA. EM txh@medicine.wisc.edu FU Eastern Cooperative Oncology Group Grant; Eastern Cooperative Oncology Group Grant to Dana-Farber Cancer Institute; Public Health Service [CA23318, CA66636, CA21115, CA21076, CA49957]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX Tien Hoang - Eastern Cooperative Oncology Group Grant to University of Wisconsin (Institutional Grant).; Suzanne E. Dahlberg - Eastern Cooperative Oncology Group Grant to Dana-Farber Cancer Institute (Institutional Grant).; This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA21076, CA49957 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 17 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUL PY 2013 VL 81 IS 1 BP 47 EP 52 DI 10.1016/j.lungcan.2013.03.018 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 174TQ UT WOS:000321178700006 PM 23611404 ER PT J AU Sung, SM Kimball, AB AF Sung, Sarah M. Kimball, Alexa B. TI Prevalence of Skin Disorders in Patients Seeking Health Care SO MAYO CLINIC PROCEEDINGS LA English DT Letter ID CANCER C1 [Sung, Sarah M.; Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sung, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 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 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2013 VL 88 IS 7 BP 776 EP 776 DI 10.1016/j.mayocp.2013.05.006 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 182XB UT WOS:000321777000021 PM 23751981 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI John Robert Vane-British Pharmacologist and Nobel Laureate SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 NR 1 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 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2013 VL 88 IS 7 BP E71 EP E71 DI 10.1016/j.mayocp.2012.01.030 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 182XB UT WOS:000321777000002 PM 23809324 ER PT J AU Huo, ZM Summers, RM Paquerault, S Lo, J Hoffmeister, J Armato, SG Freedman, MT Lin, J Lo, SCB Petrick, N Sahiner, B Fryd, D Yoshida, H Chan, HP AF Huo, Zhimin Summers, Ronald M. Paquerault, Sophie Lo, Joseph Hoffmeister, Jeffrey Armato, Samuel G., III Freedman, Matthew T. Lin, Jesse Lo, Shih-Chung Ben Petrick, Nicholas Sahiner, Berkman Fryd, David Yoshida, Hiroyuki Chan, Heang-Ping TI Quality assurance and training procedures for computer-aided detection and diagnosis systems in clinical use SO MEDICAL PHYSICS LA English DT Article DE computer-aided diagnosis; computer-aided detection; quality assurance; user training ID CT COLONOGRAPHY; SCREENING MAMMOGRAPHY; CAD; METHODOLOGIES; PERFORMANCE AB Computer-aided detection/diagnosis (CAD) is increasingly used for decision support by clinicians for detection and interpretation of diseases. However, there are no quality assurance (QA) requirements for CAD in clinical use at present. QA of CAD is important so that end users can be made aware of changes in CAD performance both due to intentional or unintentional causes. In addition, end-user training is critical to prevent improper use of CAD, which could potentially result in lower overall clinical performance. Research on QA of CAD and user training are limited to date. The purpose of this paper is to bring attention to these issues, inform the readers of the opinions of the members of the American Association of Physicists in Medicine (AAPM) CAD subcommittee, and thus stimulate further discussion in the CAD community on these topics. The recommendations in this paper are intended to be work items for AAPM task groups that will be formed to address QA and user training issues on CAD in the future. The work items may serve as a framework for the discussion and eventual design of detailed QA and training procedures for physicists and users of CAD. Some of the recommendations are considered by the subcommittee to be reasonably easy and practical and can be implemented immediately by the end users; others are considered to be "best practice" approaches, which may require significant effort, additional tools, and proper training to implement. The eventual standardization of the requirements of QA procedures for CAD will have to be determined through consensus from members of the CAD community, and user training may require support of professional societies. It is expected that high-quality CAD and proper use of CAD could allow these systems to achieve their true potential, thus benefiting both the patients and the clinicians, and may bring about more widespread clinical use of CAD for many other diseases and applications. It is hoped that the awareness of the need for appropriate CAD QA and user training will stimulate new ideas and approaches for implementing such procedures efficiently and effectively as well as funding opportunities to fulfill such critical efforts. (C) 2013 American Association of Physicists in Medicine. C1 [Huo, Zhimin] Carestream Hlth Inc, Rochester, NY 14615 USA. [Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Paquerault, Sophie; Petrick, Nicholas; Sahiner, Berkman] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Lo, Joseph] Duke Univ, Med Ctr, Durham, NC 27705 USA. [Hoffmeister, Jeffrey] ICAD Inc, Nashua, NH 03062 USA. [Armato, Samuel G., III] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Freedman, Matthew T.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Lin, Jesse] FUJIFILM Med Syst USA Inc, Stamford, CT 06902 USA. [Lo, Shih-Chung Ben] Georgetown Univ, Washington, DC 20057 USA. [Fryd, David] Riverain Med, Miamisburg, OH 45342 USA. [Yoshida, Hiroyuki] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chan, Heang-Ping] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. RP Chan, HP (reprint author), Univ Michigan, Dept Radiol, 1500 East Med Ctr Dr,MIB C477, Ann Arbor, MI 48109 USA. EM chanhp@umich.edu FU Intramural Research Program of the National Institutes of Health (NIH), Clinical Center; University of Chicago; Riverain Technologies through The University of Chicago; iCAD; Riverain Technologies through Georgetown University Medical Center FX The authors are grateful to the members and participants of the CADSC who have contributed to the stimulating discussions during many meetings and teleconferences. R.M.S. is supported by the Intramural Research Program of the National Institutes of Health (NIH), Clinical Center; the views expressed in this paper are the opinions of the authors and do not necessarily represent the views of the National Institutes of Health or Department of Health and Human Services. S. G. A. and H.Y. receive royalties and licensing fees through the University of Chicago related to CAD. S. G. A. receives research funding from Riverain Technologies through The University of Chicago. R.M.S. receives patent royalties and research support related to CAD from iCAD. M.T.F. and S.C.B.L. receive funding from Riverain Technologies through Georgetown University Medical Center. NR 14 TC 4 Z9 4 U1 1 U2 10 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 JUL PY 2013 VL 40 IS 7 AR 077001 DI 10.1118/1.4807642 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 175ZK UT WOS:000321272200059 PM 23822459 ER PT J AU Phillips, M Holdsworth, C Kalet, I Smith, W Kim, M Meyer, J AF Phillips, Mark Holdsworth, Clay Kalet, Ira Smith, Wade Kim, Minsun Meyer, Juergen TI Response to "Comment on 'When is better best? A multiobjective perspective'" [Med. Phys. 38, 1635-1640 (2011)] SO MEDICAL PHYSICS LA English DT Letter ID EVOLUTIONARY ALGORITHM; IMRT; OPTIMIZATION C1 [Phillips, Mark; Kalet, Ira; Kim, Minsun; Meyer, Juergen] Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. [Holdsworth, Clay] Brigham & Womens Hosp, Boston, MA 02115 USA. [Holdsworth, Clay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Wade] Stratton VA Med Ctr, Albany, NY 12208 USA. RP Phillips, M (reprint author), Univ Washington, Med Ctr, Dept Radiat Oncol, POB 356043, Seattle, WA 98195 USA. EM markp@u.washington.edu OI Meyer, Juergen/0000-0003-4350-2222 NR 8 TC 0 Z9 0 U1 0 U2 2 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 JUL PY 2013 VL 40 IS 7 AR 077102 DI 10.1118/1.4811107 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 175ZK UT WOS:000321272200061 PM 23822461 ER PT J AU Verburg, JM Seco, J AF Verburg, Joost M. Seco, Joao TI Dosimetric accuracy of proton therapy for chordoma patients with titanium implants SO MEDICAL PHYSICS LA English DT Article DE proton therapy; radiation therapy; cancer; chordoma; implants; computed tomography; metal artifacts; metal artifact reduction; Monte Carlo methods; dosimetry; treatment planning ID MONTE-CARLO SIMULATIONS; REACTION CROSS SECTIONS; PENCIL BEAM ALGORITHM; RANGE UNCERTAINTIES; NUCLEUS SCATTERING; RADIATION-THERAPY; MULTIPLE COULOMB; TREATMENT PLANS; HETEROGENEITIES; WATER AB Purpose: To investigate dosimetric errors in proton therapy treatment planning due to titanium implants, and to determine how these affect postoperative passively scattered proton therapy for chordoma patients with orthopedic hardware. Methods: The presence of titanium hardware near the tumor may affect the dosimetric accuracy of proton therapy. Artifacts in the computed tomography (CT) scan can cause errors in the proton stopping powers used for dose calculation, which are derived from CT numbers. Also, clinical dose calculation algorithms may not accurately simulate proton beam transport through the implants, which have very different properties as compared to human tissue. The authors first evaluated the impact of these two main issues. Dose errors introduced by metal artifacts were studied using phantoms with and without titanium inserts, and patient scans on which a metal artifact reduction method was applied. Pencil-beam dose calculations were compared to models of nuclear interactions in titanium and Monte Carlo simulations. Then, to assess the overall impact on treatment plans for chordoma, the authors compared the original clinical treatment plans to recalculated dose distributions employing both metal artifact reduction and Monte Carlo methods. Results: Dose recalculations of clinical proton fields showed that metal artifacts cause range errors up to 6 mm distal to regions affected by CT artifacts. Monte Carlo simulations revealed dose differences >10% in the high-dose area, and range differences up to 10 mm. Since these errors are mostly local in nature, the large number of fields limits the impact on target coverage in the chordoma treatment plans to a small decrease of dose homogeneity. Conclusions: In the presence of titanium implants, CT metal artifacts and the approximations of pencil-beam dose calculations cause considerable errors in proton dose calculation. The spatial distribution of the errors however limits the overall impact on passively scattered proton therapy for chordoma. c 2013 American Association of Physicists in Medicine. C1 [Verburg, Joost M.; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Verburg, Joost M.; Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Verburg, Joost M.] Eindhoven Univ Technol, Sch Med Phys & Engn, NL-5600 MB Eindhoven, Netherlands. RP Verburg, JM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jverburg@fas.harvard.edu FU Federal Share of program FX The authors would like to thank Tom Madden and Hanne Kooy, Ph.D., for providing the implementation of the pencil-beam dose calculation algorithm, and Jan Schumann, Ph.D., for the support of the TOPAS Monte Carlo code. Thanks to Juliane Daartz, Ph.D., for helpful feedback on the paper. This work was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. NR 32 TC 11 Z9 12 U1 0 U2 3 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 JUL PY 2013 VL 40 IS 7 AR 071727 DI 10.1118/1.4810942 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 175ZK UT WOS:000321272200031 PM 23822431 ER PT J AU Wang, Y Efstathiou, JA Lu, HM Sharp, GC Trofimov, A AF Wang, Yi Efstathiou, Jason A. Lu, Hsiao-Ming Sharp, Gregory C. Trofimov, Alexei TI Hypofractionated proton therapy for prostate cancer: Dose delivery uncertainty due to interfractional motion SO MEDICAL PHYSICS LA English DT Article DE prostate cancer; proton therapy; hypofractionation; interfractional motion; alpha/beta ratio; dose delivery uncertainty ID ACUTE TOXICITY; PHASE-II; RADIOTHERAPY; TRIAL; ESCALATION; SETUP AB Purpose: The alpha-to-beta (alpha/beta) ratio for prostate tumor is likely lower than that for the surrounding normal organs, such as rectum and bladder (similar to 3 Gy). As a result, hypofractionation is expected to improve the therapeutic ratio in prostate radiation therapy. However, with the use of fewer, larger fractions, the accuracy of treatment dose delivery becomes more influenced by the physical uncertainties resulting from motion and radiobiological uncertainties in the alpha/beta ratio of the prostate tumor. The purpose of this study is to evaluate the impact of interfractional motion on treatment dose delivery within the likely range of the tumor alpha/beta ratio. Methods: Serial CT images acquired at simulation and daily treatment for three prostate patients were studied retrospectively. A conventional 3D-conformal proton plan was created for each patient, delivering 25 fractions of 2 Gy to ITV1 (internal target volume, expanded from the prostate and clinically involved seminal vesicles) followed by 14 fractions to ITV2 (expanded from the prostate). The plans were renormalized for a series of hypofractionated protocols of between five and 28 fractions. The fractional doses were computed on daily CT and were mapped onto simulation CT using deformable registration. In each course, the doses from the fractions with the lowest D97% of the ITV2 were summed to approximate the lower limit (worst case) of target coverage. The uncertainty in dose and coverage was estimated as the deviation of the worst case from the nominal plan. Results: For treatments in 28 to five fractions, the uncertainty arising from interfractional motion ranged from similar to 1% to 4% for V100% and similar to 2% to 6% for D100% of the ITV2. The uncertainties in V95% and D95% were both minimal (<1%) for all protocols. For tumors with a low alpha/beta of 1.0 Gy, the treatment in five fractions could deliver an additional 21.0 and 17.4 Gy(EQD2) to 95% and 100% of the ITV2, respectively, compared to that in 28 fractions. This advantage disappeared for tumors with alpha/beta > 2.5 Gy, assuming the worst case for interfractional motion. Conclusions: In hypofractionated proton therapy for prostate cancer, the dosimetric uncertainties due to interfractional motion were minimal for the ITV2 coverage at 95% isodose level and the dose received by 95% of the ITV2. Although hypofractionation could yield an increase in equivalent dose to the target for tumors with low alpha/beta, the gain was cancelled out by the uncertainty due to interfractional motion for tumors with alpha/beta > 2.5 Gy. c 2013 American Association of Physicists in Medicine. C1 [Wang, Yi; Efstathiou, Jason A.; Lu, Hsiao-Ming; Sharp, Gregory C.; Trofimov, Alexei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Wang, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM yi.wang@mgh.harvard.edu FU Federal Share of program FX The authors would like to express their gratitude to James R. Wong, M. D., and Scott Merrick (Morristown Memorial Hospital, Morristown, NJ) for providing the patient data, and Dr. I. Frank Ciernik for his help with data processing. This study was supported by the Federal Share of program income earned by the Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. NR 15 TC 4 Z9 4 U1 0 U2 3 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 JUL PY 2013 VL 40 IS 7 AR 071714 DI 10.1118/1.4811101 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 175ZK UT WOS:000321272200018 PM 23822418 ER PT J AU Williams, CL Mishra, P Seco, J St James, S Mak, RH Berbeco, RI Lewis, JH AF Williams, Christopher L. Mishra, Pankaj Seco, Joao St James, Sara Mak, Raymond H. Berbeco, Ross I. Lewis, John H. TI A mass-conserving 4D XCAT phantom for dose calculation and accumulation SO MEDICAL PHYSICS LA English DT Article DE 4DCT; lung radiotherapy; motion management; deformable registration; IGRT ID DEFORMABLE IMAGE REGISTRATION; MONTE-CARLO; RESPIRATORY MOTION; LUNG RADIOTHERAPY; EXPERIMENTAL VALIDATION; GATED RADIOTHERAPY; DEFORMING ANATOMY; RADIATION-THERAPY; BODY RADIOTHERAPY; RECONSTRUCTION AB Purpose: The XCAT phantom is a realistic 4D digital torso phantom that is widely used in imaging and therapy research. However, lung mass is not conserved between respiratory phases of the phantom, making detailed dosimetric simulations and dose accumulation unphysical. A framework is developed to correct this issue by enforcing local mass conservation in the XCAT lung. Dose calculations are performed to assess the implications of neglecting mass conservation, and to demonstrate an application of the phantom to calculate the accumulated delivered dose in an irregularly breathing patient. Methods: A displacement vector field (DVF) between each respiratory state and a reference image is generated from the XCAT motion model and its divergence is calculated and used to correct the lung density. A series of phantoms with regular and irregular breathing (based on patient data) are generated and modified to conserve mass. Monte Carlo methods are used to simulate conventional and SBRT treatment delivery. The calculated dose is deformed and accumulated using the DVF. Results from the mass-conserving and original XCAT are compared. A 4DCT is simulated for the irregularly breathing patient, and a 4DCT-based dose estimate is compared with the accumulated delivered dose. Results: The presented framework successfully conserves mass in the XCAT lung. The spatial distribution of the lung dose was qualitatively changed by the use of a mass conservation in the XCAT; however, the corresponding DVH did not change significantly. The comparison of the delivered dose with the 4DCT-based prediction shows similar lung metric results, however dose differences of 10% can be seen in some spatial regions. Conclusions: The XCAT phantom has been successfully modified so that it conserves lung mass during respiration, enabling it to be used as a tool to perform dose accumulation studies in the lung without relying on deformable image registration. Neglecting mass conservation can result in erroneous spatial distributions of the dose in the lung. Using this tool to simulate patient treatments reveals differences between the planned dose and the calculated delivered dose for the full treatment. The software is freely available from the authors. c 2013 American Association of Physicists in Medicine. C1 [Williams, Christopher L.; Mishra, Pankaj; St James, Sara; Mak, Raymond H.; Berbeco, Ross I.; Lewis, John H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, Christopher L.; Mishra, Pankaj; St James, Sara; Mak, Raymond H.; Berbeco, Ross I.; Lewis, John H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Seco, Joao] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Williams, CL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM cwilliams@lroc.harvard.edu FU Radiological Society of North America [RSCH1206]; National Cancer Institute [R21CA156068] FX The authors would like to thank Dr. Seiko Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan and Dr. Hiroki Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan for sharing the patient tumor motion dataset with us. The project described was supported by Award Nos. RSCH1206 (J.H.L.) from the Radiological Society of North America and R21CA156068 (R.I.B.) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 41 TC 5 Z9 5 U1 0 U2 11 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 JUL PY 2013 VL 40 IS 7 AR 071728 DI 10.1118/1.4811102 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 175ZK UT WOS:000321272200032 PM 23822432 ER PT J AU Kharbanda, A Rajabi, H Jin, CN Raina, D Kufe, D AF Kharbanda, Akriti Rajabi, Hasan Jin, Caining Raina, Deepak Kufe, Donald TI Oncogenic MUC1-C Promotes Tamoxifen Resistance in Human Breast Cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; ENDOCRINE RESISTANCE; AKT ACTIVITY; ONCOPROTEIN; CELLS; TRANSCRIPTION; ACTIVATION; MECHANISMS; PATHWAYS; COACTIVATOR AB Tamoxifen resistance of estrogen receptor-positive (ER+) breast cancer cells has been linked in part to activation of receptor tyrosine kinases, such as HER2, and the PI3K-AKT pathway. Mucin 1 (MUC1) is aberrantly overexpressed in about 90% of human breast cancers, and the oncogenic MUC1-C subunit is associated with ER alpha. The present studies using HER2 overexpressing BT-474 breast cancer cells, which are constitutively resistant to tamoxifen, demonstrate that silencingMUC1-C is associated with (i) downregulation of p-HER2 and (ii) sensitivity to tamoxifen-induced growth inhibition and loss of clonogenic survival. In contrast, overexpression of MUC1-C in tamoxifen-sensitive MCF-7 breast cancer cells resulted in upregulation of p-AKT and tamoxifen resistance. We show that MUC1-C forms complexes with ER alpha on the estrogenresponsive promoter of Rab31 and that MUC1-C blocks tamoxifen-induced decreases in ER alpha occupancy. MUC1-C also attenuated tamoxifen-induced decreases in (i) recruitment of the coactivator CREB binding protein, (ii) Rab31 promoter activation, and (iii) Rab31 mRNA and protein levels. The importance of MUC1C is further supported by the demonstration that targeting MUC1-C with the cell-penetrating peptide inhibitor, GO-203, sensitized tamoxifen-resistant cells to tamoxifen treatment. Moreover, we show that targeting MUC1-C in combination with tamoxifen is highly synergistic in the treatment of tamoxifen-resistant breast cancer cells. Combined, these findings indicate that MUC1-C contributes to tamoxifen resistance. C1 [Kharbanda, Akriti; Rajabi, Hasan; Jin, Caining; Raina, Deepak; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute of the NIH [CA97098, CA166480] FX Research reported in this publication was supported by the National Cancer Institute of the NIH under award numbers CA97098 and CA166480. NR 40 TC 14 Z9 15 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUL PY 2013 VL 11 IS 7 BP 714 EP 723 DI 10.1158/1541-7786.MCR-12-0668 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 185DL UT WOS:000321945300003 PM 23538857 ER PT J AU Fragomeni, RAS Chung, HW Landesman, Y Senapedis, W Saint-Martin, JR Tsao, HS Flaherty, KT Shacham, S Kauffman, M Cusack, JC AF Fragomeni, Roberto A. Salas Chung, Hye Won Landesman, Yosef Senapedis, William Saint-Martin, Jean-Richard Tsao, Hensin Flaherty, Keith T. Shacham, Sharon Kauffman, Michael Cusack, James C. TI CRM1 and BRAF Inhibition Synergize and Induce Tumor Regression in BRAF-Mutant Melanoma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NUCLEAR EXPORT; LEPTOMYCIN-B; CANCER; EXPRESSION; APOPTOSIS; CELLS; FIBROBLASTS; PROGNOSIS; SURVIVAL AB Resistance to BRAF inhibitor therapy places priority on developing BRAF inhibitor-based combinations that will overcome de novo resistance and prevent the emergence of acquired mechanisms of resistance. The CRM1 receptor mediates the nuclear export of critical proteins required for melanoma proliferation, survival, and drug resistance. We hypothesize that by inhibiting CRM1-mediated nuclear export, we will alter the function of these proteins resulting in decreased melanoma viability and enhanced BRAF inhibitor antitumoral effects. To test our hypothesis, selective inhibitors of nuclear export (SINE) analogs KPT-185, KPT-251, KPT-276, and KPT-330 were used to induce CRM1 inhibition. Analogs PLX-4720 and PLX-4032 were used as BRAF inhibitors. Compounds were tested in xenograft and in vitro melanoma models. In vitro, we found CRM1 inhibition decreases melanoma cell proliferation independent of BRAF mutation status and synergistically enhances the effects of BRAF inhibition on BRAF-mutant melanoma by promoting cell-cycle arrest and apoptosis. In melanoma xenograft models, CRM1 inhibition reduces tumor growth independent of BRAF or NRAS status and induces complete regression of BRAF V600E tumors when combined with BRAF inhibition. Mechanistic studies show that CRM1 inhibition was associated with p53 stabilization and retinoblastoma protein (pRb) and survivin modulation. Furthermore, we found that BRAF inhibition abrogates extracellular signal-regulated kinase phosphorylation associated with CRM1 inhibition, which may contribute to the synergy of the combination. In conclusion, CRM1 inhibition impairs melanoma survival in both BRAF-mutant and wild-type melanoma. The combination of CRM1 and BRAF inhibition synergizes and induces melanoma regression in BRAF-mutant melanoma. (C) 2013 AACR. C1 [Fragomeni, Roberto A. Salas; Chung, Hye Won; Tsao, Hensin; Flaherty, Keith T.; Cusack, James C.] Harvard Univ, Sch Med, Boston, MA USA. [Fragomeni, Roberto A. Salas; Chung, Hye Won; Cusack, James C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Landesman, Yosef; Senapedis, William; Saint-Martin, Jean-Richard; Shacham, Sharon; Kauffman, Michael] Karyopharm Therapeut, Natick, MA USA. RP Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7th Floor,55 Fruit St, Boston, MA 02114 USA. EM jcusack@partners.org NR 27 TC 19 Z9 19 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2013 VL 12 IS 7 BP 1171 EP 1179 DI 10.1158/1535-7163.MCT-12-1171 PG 9 WC Oncology SC Oncology GA 179BQ UT WOS:000321492700003 ER PT J AU Bardeleben, C Sharma, S Reeve, JR Bassilian, S Frost, P Hoang, B Shi, YJ Lichtenstein, A AF Bardeleben, Carolyne Sharma, Sanjai Reeve, Joseph R. Bassilian, Sara Frost, Patrick Hoang, Bao Shi, Yijiang Lichtenstein, Alan TI Metabolomics Identifies Pyrimidine Starvation as the Mechanism of 5-Aminoimidazole-4-Carboxamide-1-beta-Riboside-Induced Apoptosis in Multiple Myeloma Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACTIVATED PROTEIN-KINASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHOSPHONACETYL-L-ASPARTATE; LYMPHOID-CELLS; AICA-RIBOSIDE; OROTIC-ACID; AMPK; ADENOSINE; INHIBITION; DEXAMETHASONE AB To investigate the mechanism by which 5-aminoimidazole-4-carboxamide-1-beta-riboside (AICAr) induces apoptosis in multiple myeloma cells, we conducted an unbiased metabolomics screen. AICAr had selective effects on nucleotide metabolism, resulting in an increase in purine metabolites and a decrease in pyrimidine metabolites. The most striking abnormality was a 26-fold increase in orotate associated with a decrease in uridine monophosphate (UMP) levels, indicating an inhibition of UMP synthetase (UMPS), the last enzyme in the de novo pyrimidine biosynthetic pathway, which produces UMP from orotate and 5-phosphoribosyl-alpha-pyrophosphate (PRPP). As all pyrimidine nucleotides can be synthesized from UMP, this suggested that the decrease in UMP would lead to pyrimidine starvation as a possible cause of AICAr-induced apoptosis. Exogenous pyrimidines uridine, cytidine, and thymidine, but not purines adenosine or guanosine, rescued multiple myeloma cells from AICAr-induced apoptosis, supporting this notion. In contrast, exogenous uridine had no protective effect on apoptosis resulting from bortezomib, melphalan, or metformin. Rescue resulting from thymidine add-back indicated apoptosis was induced by limiting DNA synthesis rather than RNA synthesis. DNA replicative stress was identified by associated H2A. X phosphorylation in AICAr-treated cells, which was also prevented by uridine add-back. Although phosphorylation of AICAr by adenosine kinase was required to induce multiple myeloma cell death, apoptosis was not associated with AMP-activated kinase activation or mTORC1 inhibition. A possible explanation for inhibition of UMP synthase activity by AICAr was a depression in cellular levels of PRPP, a substrate of UMP synthase. These data identify pyrimidine biosynthesis as a potential molecular target for future therapeutics in multiple myeloma cells. (C) 2013 AACR. C1 [Bardeleben, Carolyne; Sharma, Sanjai; Frost, Patrick; Hoang, Bao; Shi, Yijiang; Lichtenstein, Alan] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Ctr, Div Hematology Oncol, Los Angeles, CA USA. [Lichtenstein, Alan] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Reeve, Joseph R.; Bassilian, Sara] Univ Calif Los Angeles, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. RP Lichtenstein, A (reprint author), Greater Los Angeles VA Healthcare Ctr, Div Hematol Oncol, 111H,VA West Med Ctr,11301 Wilshire BLVD, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov FU NIH [CA132778, CA111448, CA168491]; Research funds of the Multiple Myeloma Research Foundation; Research Funds of the Veteran's Administration; NIH Center Grant; CURE: Digestive Diseases Research Center [DK-41301]; Peptidomic, RIA and Proteomic Core FX This work was supported in part by NIH grants CA132778, CA111448, CA168491, Research funds of the Multiple Myeloma Research Foundation and Research Funds of the Veteran's Administration to A. Lichtenstein and in part by NIH Center Grant, CURE: Digestive Diseases Research Center DK-41301 Peptidomic, RIA and Proteomic Core (J.R. Reeve). NR 48 TC 4 Z9 4 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2013 VL 12 IS 7 BP 1310 EP 1321 DI 10.1158/1535-7163.MCT-12-1042 PG 12 WC Oncology SC Oncology GA 179BQ UT WOS:000321492700016 PM 23585020 ER PT J AU Harvey, CJ Wucherpfennig, KW AF Harvey, Christopher J. Wucherpfennig, Kai W. TI Cracking the code of human T-cell immunity SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID MASS CYTOMETRY; CONTINUUM; RESPONSES C1 [Harvey, Christopher J.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Program Immunol, Boston, MA 02115 USA. RP Harvey, CJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2013 VL 31 IS 7 BP 608 EP 609 DI 10.1038/nbt.2626 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 180FS UT WOS:000321579700015 PM 23839145 ER PT J AU Taipale, M Krykbaeva, I Whitesell, L Santagata, S Zhang, JM Liu, QS Gray, NS Lindquist, S AF Taipale, Mikko Krykbaeva, Irina Whitesell, Luke Santagata, Sandro Zhang, Jianming Liu, Qingsong Gray, Nathanael S. Lindquist, Susan TI Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells SO NATURE BIOTECHNOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PROTEIN-TYROSINE KINASE; BCR-ABL; INFANTILE FIBROSARCOMA; QUANTITATIVE-ANALYSIS; PONATINIB AP24534; MAMMALIAN-CELLS; INTERACTION MAP; BINDING-SITE; RECEPTOR AB The interaction between the HSP90 chaperone and its client kinases is sensitive to the conformational status of the kinase, and stabilization of the kinase fold by small molecules strongly decreases chaperone interaction. Here we exploit this observation and assay small-molecule binding to kinases in living cells, using chaperones as 'thermodynamic sensors'. The method allows determination of target specificities of both ATP-competitive and allosteric inhibitors in the kinases' native cellular context in high throughput. We profile target specificities of 30 diverse kinase inhibitors against >300 kinases. Demonstrating the value of the assay, we identify ETV6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori). Crizotinib inhibits proliferation of ETV6-NTRK3-dependent tumor cells with nanomolar potency and induces the regression of established tumor xenografts in mice. Finally, we show that our approach is applicable to other chaperone and target classes by assaying HSP70/steroid hormone receptor and CDC37/kinase interactions, suggesting that chaperone interactions will have broad application in detecting drug-target interactions in vivo. C1 [Taipale, Mikko; Krykbaeva, Irina; Whitesell, Luke; Santagata, Sandro; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Jianming; Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Jianming; Liu, Qingsong; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lindquist, Susan] MIT, Dept Biol, Cambridge, MA USA. [Lindquist, Susan] Howard Hughes Med Inst, Cambridge, MA USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist_admin@wi.mit.edu OI Taipale, Mikko/0000-0003-3811-1761; liu, qing song/0000-0002-7829-2547 FU Human Frontier Science Programme long-term fellowship; US National Institutes of Health (NIH) [UL1-DE019585]; NIH [RL1-GM084437, RL1-CA133834, RL1-HG004671] FX We thank the Lindquist laboratory members for valuable discussions and comments on the manuscript. We also thank M. Azam (Cincinnati Children's Hospital Medical Center) for providing mutant BCR-ABL clones and P. Thiru, I. Barrasa and G. Bell (Whitehead Institute) for help with primer design and statistical analysis. M. T. was supported by Human Frontier Science Programme long-term fellowship. S. L. is a Howard Hughes Medical Institute investigator. Support for this study was also provided by the US National Institutes of Health (NIH) Genomics Based Drug Discovery-Driving Medical Projects grant UL1-DE019585, administratively linked to NIH grants RL1-GM084437, RL1-CA133834 and RL1-HG004671. NR 46 TC 44 Z9 45 U1 1 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2013 VL 31 IS 7 BP 630 EP U90 DI 10.1038/nbt.2620 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 180FS UT WOS:000321579700020 PM 23811600 ER PT J AU Wang, GC Lunardi, A Zhang, JW Chen, ZB Ala, U Webster, KA Tay, Y Gonzalez-Billalabeitia, E Egia, A Shaffer, DR Carver, B Liu, XS Taulli, R Kuo, WP Nardella, C Signoretti, S Cordon-Cardo, C Gerald, WL Pandolfi, PP AF Wang, Guocan Lunardi, Andrea Zhang, Jiangwen Chen, Zhenbang Ala, Ugo Webster, Kaitlyn A. Tay, Yvonne Gonzalez-Billalabeitia, Enrique Egia, Ainara Shaffer, David R. Carver, Brett Liu, Xue-Song Taulli, Riccardo Kuo, Winston Patrick Nardella, Caterina Signoretti, Sabina Cordon-Cardo, Carlos Gerald, William L. Pandolfi, Pier Paolo TI Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion SO NATURE GENETICS LA English DT Article ID MELANOMA INHIBITORY-ACTIVITY; GENE-EXPRESSION ANALYSIS; ZINC-FINGER PROTEIN; MALIGNANT-MELANOMA; COLORECTAL-CANCER; DMBT1 EXPRESSION; UP-REGULATION; IN-VIVO; PROGRESSION; CELLS AB Zbtb7a has previously been described as a powerful proto-oncogene. Here we unexpectedly demonstrate that Zbtb7a has a critical oncosuppressive role in the prostate. Prostate-specific inactivation of Zbtb7a leads to a marked acceleration of Pten loss-driven prostate tumorigenesis through bypass of Pten loss-induced cellular senescence (PICS). We show that ZBTB7A physically interacts with SOX9 and functionally antagonizes its transcriptional activity on key target genes such as MIA, which is involved in tumor cell invasion, and H19, a long noncoding RNA precursor for an RB-targeting microRNA. Inactivation of Zbtb7a in vivo leads to Rb downregulation, PICS bypass and invasive prostate cancer. Notably, we found that ZBTB7A is genetically lost, as well as downregulated at both the mRNA and protein levels, in a subset of human advanced prostate cancers. Thus, we identify ZBTB7A as a context-dependent cancer gene that can act as an oncogene in some contexts but also has oncosuppressive-like activity in Pten-null tumors. C1 [Wang, Guocan; Lunardi, Andrea; Ala, Ugo; Webster, Kaitlyn A.; Tay, Yvonne; Gonzalez-Billalabeitia, Enrique; Egia, Ainara; Liu, Xue-Song; Taulli, Riccardo; Nardella, Caterina; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, Canc Genet Program, Boston, MA 02115 USA. [Wang, Guocan; Lunardi, Andrea; Ala, Ugo; Webster, Kaitlyn A.; Tay, Yvonne; Gonzalez-Billalabeitia, Enrique; Egia, Ainara; Liu, Xue-Song; Taulli, Riccardo; Nardella, Caterina; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Wang, Guocan; Lunardi, Andrea; Ala, Ugo; Webster, Kaitlyn A.; Tay, Yvonne; Gonzalez-Billalabeitia, Enrique; Egia, Ainara; Liu, Xue-Song; Taulli, Riccardo; Nardella, Caterina; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Wang, Guocan] Cornell Univ, Weill Grad Sch Med Sci, Biochem Cell & Mol Biol Program, New York, NY 10021 USA. [Wang, Guocan; Chen, Zhenbang; Shaffer, David R.; Nardella, Caterina; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA. [Wang, Guocan; Chen, Zhenbang; Shaffer, David R.; Nardella, Caterina; Cordon-Cardo, Carlos; Gerald, William L.; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Zhang, Jiangwen] Harvard Univ, Ctr Syst Biol, Fac Arts & Sci, Cambridge, MA 02138 USA. [Carver, Brett] Mem Sloan Kettering Canc Ctr, Dept Surg, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Nardella, Caterina] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Preclin Murine Pharmacogenet Facil, Boston, MA 02215 USA. [Signoretti, Sabina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, Canc Genet Program, Boston, MA 02115 USA. EM ppandolf@bidmc.harvard.edu RI Ala, Ugo/K-2029-2016 OI Ala, Ugo/0000-0001-5408-6397 FU Istituto Toscano Tumori (ITT, Italy); Mouse Models of Human Cancer Consortium (MMHCC) National Cancer Institute (NCI) [RC2 CA147940-01]; US National Institutes of Health (NIH) [R01 CA102142-7] FX We are grateful to P. Berta (Institut de Genetique Humaine), B. de Crombrugghe (University of Texas MD Anderson Cancer Center) and A. Ullrich (Max Planck Institute) for reagents. We would also like to thank R. Hobbs, M. Dalynicolosi and T. Garvey for editing and critical reading of the manuscript, as well as X. Yuan and all members of the Pandolfi laboratory for insightful comments and discussion. A. L. has been supported in part by a fellowship from the Istituto Toscano Tumori (ITT, Italy). R. T. has been granted leave of absence from the Department of Oncology, Universita degli Studi di Torino (Italy). This work has been supported by a Mouse Models of Human Cancer Consortium (MMHCC) National Cancer Institute (NCI) grant (RC2 CA147940-01) and a US National Institutes of Health (NIH) grant (R01 CA102142-7) to P.P.P. NR 72 TC 41 Z9 43 U1 1 U2 19 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 JUL PY 2013 VL 45 IS 7 BP 739 EP + DI 10.1038/ng.2654 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 172LQ UT WOS:000321005200008 PM 23727861 ER PT J AU Lunardi, A Ala, U Epping, MT Salmena, L Clohessy, JG Webster, KA Wang, GC Mazzucchelli, R Bianconi, M Stack, EC Lis, R Patnaik, A Cantley, LC Bubley, G Cordon-Cardo, C Gerald, WL Montironi, R Signoretti, S Loda, M Nardella, C Pandolfi, PP AF Lunardi, Andrea Ala, Ugo Epping, Mirjam T. Salmena, Leonardo Clohessy, John G. Webster, Kaitlyn A. Wang, Guocan Mazzucchelli, Roberta Bianconi, Maristella Stack, Edward C. Lis, Rosina Patnaik, Akash Cantley, Lewis C. Bubley, Glenn Cordon-Cardo, Carlos Gerald, William L. Montironi, Rodolfo Signoretti, Sabina Loda, Massimo Nardella, Caterina Pandolfi, Pier Paolo TI A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer SO NATURE GENETICS LA English DT Article ID GENE-EXPRESSION ANALYSIS; PANCREATIC-CANCER; APOPTOSIS; PROGRESSION; XAF1; TARGET; CELLS; P53; DUTASTERIDE; SIGNATURES AB Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten loss-driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed with deletion of either Trp53 or Zbtb7a together with Pten, leading to the development of castration-resistant prostate cancer (CRPC). Mechanistically, the integrated acquisition of data from mouse models and patients identifies the expression patterns of XAF1, XIAP and SRD5A1 as a predictive and actionable signature for CRPC. Notably, we show that combined inhibition of XIAP, SRD5A1 and AR pathways overcomes castration resistance. Thus, our co-clinical approach facilitates the stratification of patients and the development of tailored and innovative therapeutic treatments. C1 [Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T.; Salmena, Leonardo; Clohessy, John G.; Webster, Kaitlyn A.; Wang, Guocan; Nardella, Caterina; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Genet Program,Dept Med & Pathol,Med Sch, Boston, MA 02215 USA. [Ala, Ugo] Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, Turin, Italy. [Salmena, Leonardo; Clohessy, John G.; Wang, Guocan; Nardella, Caterina; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA. [Salmena, Leonardo; Clohessy, John G.; Wang, Guocan; Gerald, William L.; Nardella, Caterina; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Dept Pathol, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Wang, Guocan] Cornell Univ, Weill Grad Sch Med Sci, Biochem Cell & Mol Biol Program, New York, NY 10021 USA. [Mazzucchelli, Roberta; Montironi, Rodolfo] Polytech Univ Marche Reg Ancona, United Hosp, Inst Pathol Anat & Histopathol, Ancona, Italy. [Bianconi, Maristella] Polytech Univ Marche Reg Ancona, United Hosp, Postgrad Sch Med Oncol, Clin Oncol, Ancona, Italy. [Stack, Edward C.; Lis, Rosina; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Stack, Edward C.; Lis, Rosina; Signoretti, Sabina; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stack, Edward C.; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Patnaik, Akash; Bubley, Glenn] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Cordon-Cardo, Carlos] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Loda, Massimo] Broad Inst Harvard & MIT, Cambridge, MA USA. [Nardella, Caterina] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Preclin Murine Pharmacogenet Facil, Boston, MA 02215 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Genet Program,Dept Med & Pathol,Med Sch, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu RI Cantley, Lewis/D-1800-2014; Ala, Ugo/K-2029-2016; OI Cantley, Lewis/0000-0002-1298-7653; Ala, Ugo/0000-0001-5408-6397; Bianconi, Maristella/0000-0003-3475-2529 FU National Cancer Institute Cancer Center Support grant (US National Institutes of Health (NIH)) [5 P30 CA06516]; Italian Association for Cancer Research (AIRC) [IG-9408]; Istituto Toscano Tumori (ITT, Italy); Mouse Models of Human Cancer Consortium/National Cancer Institute [RC2 CA147940-01]; A. David Mazzone Research Awards Program, Project Development Award FX We would like to thank current members of the Pandolfi laboratory for critical discussion and T. Garvey for insightful editing. We are grateful to the Preclinical Murine Pharmacogenetics Facility at Beth Israel Deaconess Medical Center and the Dana-Farber/Harvard Cancer Center for expert support in all aspects related to the work in mice. The Dana-Farber/Harvard Cancer Center is supported in part by a National Cancer Institute Cancer Center Support grant (US National Institutes of Health (NIH) 5 P30 CA06516). We also thank C. Abate-Shen (Columbia University) for kindly providing the antibody to Probasin and the Small-Animal Imaging Facility at Beth Israel Deaconess Medical Center for the MRI work. Additionally, we are grateful to G. Fedele and X. Wu from the Loda laboratory and the Center for Molecular Oncologic Pathology at Dana-Farber/Brigham and Women's for their technical support in the generation, staining and analysis of the TMA. U. A. has been supported by a fellowship from the Italian Association for Cancer Research (AIRC) under grant IG-9408. A. L. has been supported in part by a fellowship from the Istituto Toscano Tumori (ITT, Italy). This work has been supported through the Mouse Models of Human Cancer Consortium/National Cancer Institute grant (RC2 CA147940-01) and the A. David Mazzone Research Awards Program, Project Development Award to P.P.P. NR 49 TC 55 Z9 55 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2013 VL 45 IS 7 BP 747 EP + DI 10.1038/ng.2650 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 172LQ UT WOS:000321005200009 PM 23727860 ER PT J AU Carvill, GL Heavin, SB Yendle, SC McMahon, JM O'Roak, BJ Cook, J Khan, A Dorschner, MO Weaver, M Calvert, S Malone, S Wallace, G Stanley, T Bye, AME Bleasel, A Howell, KB Kivity, S Mackay, MT Rodriguez-Casero, V Webster, R Korczyn, A Afawi, Z Zelnick, N Lerman-Sagie, T Lev, D Moller, RS Gill, D Andrade, DM Freeman, JL Sadleir, LG Shendure, J Berkovic, SF Scheffer, IE Mefford, HC AF Carvill, Gemma L. Heavin, Sinead B. Yendle, Simone C. McMahon, Jacinta M. O'Roak, Brian J. Cook, Joseph Khan, Adiba Dorschner, Michael O. Weaver, Molly Calvert, Sophie Malone, Stephen Wallace, Geoffrey Stanley, Thorsten Bye, Ann M. E. Bleasel, Andrew Howell, Katherine B. Kivity, Sara Mackay, Mark T. Rodriguez-Casero, Victoria Webster, Richard Korczyn, Amos Afawi, Zaid Zelnick, Nathanel Lerman-Sagie, Tally Lev, Dorit Moller, Rikke S. Gill, Deepak Andrade, Danielle M. Freeman, Jeremy L. Sadleir, Lynette G. Shendure, Jay Berkovic, Samuel F. Scheffer, Ingrid E. Mefford, Heather C. TI Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 SO NATURE GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; SODIUM-CHANNEL; MENTAL-RETARDATION; GENE SCN2A; MICRODELETION; SEIZURES; EPILEPSIES; PHENOTYPE; DELETIONS AB Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders. C1 [Carvill, Gemma L.; Cook, Joseph; Khan, Adiba; Mefford, Heather C.] Univ Washington, Div Med Genet, Dept Pediat, Seattle, WA 98195 USA. [Heavin, Sinead B.; Yendle, Simone C.; McMahon, Jacinta M.; Berkovic, Samuel F.; Scheffer, Ingrid E.] Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Melbourne, Vic, Australia. [O'Roak, Brian J.; Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Dorschner, Michael O.; Weaver, Molly] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Dorschner, Michael O.; Weaver, Molly] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Calvert, Sophie; Malone, Stephen; Wallace, Geoffrey] Royal Childrens Hosp, Neurosci Childrens Hlth Queensland, Brisbane, Qld, Australia. [Calvert, Sophie; Malone, Stephen; Wallace, Geoffrey] Univ Queensland, Mater Childrens Hosp, Neurosci Childrens Hlth Queensland, Brisbane, Qld 4101, Australia. [Stanley, Thorsten; Sadleir, Lynette G.] Univ Otago, Sch Med & Hlth Sci, Dept Paediat, Wellington, New Zealand. [Bye, Ann M. E.] Univ New S Wales, Dept Paediat Neurol, Sydney Childrens Hosp, Sydney, NSW, Australia. [Bleasel, Andrew] Univ Sydney, Westmead Hosp, Dept Neurol, Sydney, NSW 2006, Australia. [Howell, Katherine B.; Mackay, Mark T.; Freeman, Jeremy L.; Scheffer, Ingrid E.] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia. [Kivity, Sara] Schneider Childrens Med Ctr Israel, Epilepsy Unit, Petah Tiqwa, Israel. [Mackay, Mark T.; Freeman, Jeremy L.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Mackay, Mark T.; Scheffer, Ingrid E.] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia. [Rodriguez-Casero, Victoria] Monash Med Ctr, Melbourne, Vic, Australia. [Webster, Richard; Gill, Deepak] Childrens Hosp Westmead, TY Nelson Dept Neurol, Sydney, NSW, Australia. [Korczyn, Amos] Tel Aviv Univ, Dept Neurol, IL-69978 Tel Aviv, Israel. [Afawi, Zaid] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel. [Zelnick, Nathanel] Technion Israel Inst Technol, Fac Med, Carmel Med Ctr, Dept Pediat, Haifa, Israel. [Lerman-Sagie, Tally; Lev, Dorit] Wolfson Med Ctr, Metab Neurogenet Serv, Holon, Israel. [Lerman-Sagie, Tally; Moller, Rikke S.] Danish Epilepsy Ctr, Dianalund, Denmark. [Andrade, Danielle M.] Univ Toronto, Toronto Western Hosp, Dept Med, Div Neurol,Krembil Neurosci Program, Toronto, ON M5T 2S8, Canada. [Scheffer, Ingrid E.] Florey Inst, Melbourne, Vic, Australia. RP Mefford, HC (reprint author), Univ Washington, Div Med Genet, Dept Pediat, Seattle, WA 98195 USA. EM scheffer@unimelb.edu.au; hmefford@uw.edu RI Korczyn, Amos/C-3461-2017; Wallace, Geoff/H-1252-2013; Scheffer, Ingrid/G-1668-2013 OI Korczyn, Amos/0000-0003-0125-2579; McMahon, Jacinta/0000-0001-8891-0049; Berkovic, Samuel/0000-0003-4580-841X; O'Roak, Brian/0000-0002-4141-0095; Wallace, Geoff/0000-0001-9306-3542; Shendure, Jay/0000-0002-1516-1865; Scheffer, Ingrid/0000-0002-2311-2174 FU US National Institutes of Health (NIH; National Institute of Neurological Disorders and Stroke (NINDS)) [1R01NS069605]; Burroughs Wellcome Fund Career Award for Medical Scientists; National Health and Medical Research Council of Australia [628952, 1006110]; Health Research Council of New Zealand FX We thank the individuals with epileptic encephalopathies and their families for participating in our research. H. C. M. is supported by a grant from the US National Institutes of Health (NIH; National Institute of Neurological Disorders and Stroke (NINDS) 1R01NS069605) and is a recipient of a Burroughs Wellcome Fund Career Award for Medical Scientists. This work was supported by the National Health and Medical Research Council of Australia (program grant 628952 to S. F. B. and I. E. S., practitioner fellowship 1006110 to I. E. S.) and a Health Research Council of New Zealand project grant to L.G.S. NR 37 TC 187 Z9 193 U1 2 U2 30 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 JUL PY 2013 VL 45 IS 7 BP 825 EP U158 DI 10.1038/ng.2646 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 172LQ UT WOS:000321005200021 PM 23708187 ER PT J AU Xie, MC Hong, CB Zhang, B Lowdon, RF Xing, XY Li, DF Zhou, X Lee, HJ Maire, CL Ligon, KL Gascard, P Sigaroudinia, M Tlsty, TD Kadlecek, T Weiss, A O'Geen, H Farnham, PJ Madden, PAF Mungall, AJ Tam, A Kamoh, B Cho, S Moore, R Hirst, M Marra, MA Costello, JF Wang, T AF Xie, Mingchao Hong, Chibo Zhang, Bo Lowdon, Rebecca F. Xing, Xiaoyun Li, Daofeng Zhou, Xin Lee, Hyung Joo Maire, Cecile L. Ligon, Keith L. Gascard, Philippe Sigaroudinia, Mahvash Tlsty, Thea D. Kadlecek, Theresa Weiss, Arthur O'Geen, Henriette Farnham, Peggy J. Madden, Pamela A. F. Mungall, Andrew J. Tam, Angela Kamoh, Baljit Cho, Stephanie Moore, Richard Hirst, Martin Marra, Marco A. Costello, Joseph F. Wang, Ting TI DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape SO NATURE GENETICS LA English DT Article ID GENE REGULATORY NETWORKS; ALTERNATIVE PROMOTERS; REPETITIVE ELEMENTS; HUMAN GENOMES; STEM-CELLS; EVOLUTION; BINDING; METHYLATION; INSERTION; SEQUENCE AB Transposable element (TE)-derived sequences comprise half of the human genome and DNA methylome and are presumed to be densely methylated and inactive. Examination of genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues identified unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the relevant tissue type, and their expression correlated strongly with hypomethylation within the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks, including monomethylation of histone H3 at lysine 4 (H3K4me1) and occupancy by p300, and a majority exhibited enhancer activity in reporter gene assays. Many such TEs also harbored binding sites for transcription factors that are important for tissue-specific functions and showed evidence of evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks and may have acquired tissue-specific epigenetic regulation. C1 [Xie, Mingchao; Zhang, Bo; Lowdon, Rebecca F.; Xing, Xiaoyun; Li, Daofeng; Zhou, Xin; Lee, Hyung Joo; Wang, Ting] Washington Univ, Sch Med, Dept Genet, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA. [Hong, Chibo; Costello, Joseph F.] Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Maire, Cecile L.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gascard, Philippe; Sigaroudinia, Mahvash; Tlsty, Thea D.] Univ Calif San Francisco, Dept Pathol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94140 USA. [Kadlecek, Theresa; Weiss, Arthur] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA. [Weiss, Arthur] Univ Calif San Francisco, Div Rheumatol, San Francisco, CA USA. [O'Geen, Henriette] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Farnham, Peggy J.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. [Madden, Pamela A. F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Mungall, Andrew J.; Tam, Angela; Kamoh, Baljit; Cho, Stephanie; Moore, Richard; Hirst, Martin; Marra, Marco A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Hirst, Martin] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada. RP Costello, JF (reprint author), Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM jcostello@cc.ucsf.edu; twang@genetics.wustl.edu RI Lee, Hyung Joo/D-1398-2009; Tang, Macy/B-9798-2014; Zhang, Bo/A-6874-2011; Li, Daofeng/E-5386-2011; Hirst, Martin/B-7684-2016; Marra, Marco/B-5987-2008; OI Farnham, Peggy/0000-0003-4469-7914; Lee, Hyung Joo/0000-0002-7030-5390; Zhang, Bo/0000-0003-2962-5314; Li, Daofeng/0000-0001-7492-3703; Kadlecek, Theresa/0000-0002-1020-8169 FU US National Institutes of Health (NIH) Roadmap Epigenomics Program; National Institute on Drug Abuse (NIDA); National Institute of Environmental Health Sciences (NIEHS); US NIH [5U01ES017154, P01CA095616, P01CA142536, P50CA134254]; NIDA R25 program [DA027995]; March of Dimes Foundation; Edward Mallinckrodt Jr. Foundation FX We thank the many collaborators at the Reference Epigenome Mapping Centers (REMCs), the Epigenome Data Analysis and Coordination Center and the NCBI who have generated and processed data that were used in this project. We acknowledge the dedicated system administrators at the Washington University Center for Genome Sciences and Systems Biology who have provided an excellent computing environment. We thank the UCSC Genome Browser bioinformatics team for providing processed ENCODE data. We acknowledge support from the US National Institutes of Health (NIH) Roadmap Epigenomics Program, sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). J.F.C., T. W., P.J.F. and M. H. are supported by US NIH grant 5U01ES017154. B.Z. and X.Z. are supported by the NIDA R25 program DA027995. K. L. L. and C. L. M. are supported by US NIH grants P01CA095616 and P01CA142536. T. W. is supported in part by the March of Dimes Foundation, the Edward Mallinckrodt Jr. Foundation, US NIH grant P50CA134254 and a generous start-up package from the Department of Genetics at the Washington University School of Medicine. NR 58 TC 69 Z9 71 U1 3 U2 37 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 JUL PY 2013 VL 45 IS 7 BP 836 EP U172 DI 10.1038/ng.2649 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 172LQ UT WOS:000321005200023 PM 23708189 ER PT J AU Sugimoto, H LeBleu, VS Bosukonda, D Keck, P Taduri, G Bechtel, W Okada, H Carlson, W Bey, P Rusckowski, M Tampe, B Tampe, D Kanasaki, K Zeisberg, M Kalluri, R AF Sugimoto, Hikaru LeBleu, Valerie S. Bosukonda, Dattatreyamurty Keck, Peter Taduri, Gangadhar Bechtel, Wibke Okada, Hirokazu Carlson, William Bey, Philippe Rusckowski, Mary Tampe, Bjoern Tampe, Desiree Kanasaki, Keizo Zeisberg, Michael Kalluri, Raghu TI Regarding the mechanism of action of a proposed peptide agonist of the bone morphogenetic protein receptor activin-like kinase 3 Reply SO NATURE MEDICINE LA English DT Letter ID CRYSTAL-STRUCTURE; TRANSFORMING GROWTH-FACTOR-BETA-2; BETA SUPERFAMILY; COMPLEX; REPAIR; CELLS C1 [Sugimoto, Hikaru; LeBleu, Valerie S.; Taduri, Gangadhar; Bechtel, Wibke; Okada, Hirokazu; Kanasaki, Keizo; Zeisberg, Michael; Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA. [Sugimoto, Hikaru; LeBleu, Valerie S.; Taduri, Gangadhar; Bechtel, Wibke; Okada, Hirokazu; Kanasaki, Keizo; Zeisberg, Michael; Kalluri, Raghu] Harvard Univ, Sch Med, Boston, MA USA. [Bosukonda, Dattatreyamurty; Keck, Peter; Carlson, William] Thrasos Innovation Inc, Montreal, PQ, Canada. [Carlson, William; Bey, Philippe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02115 USA. [Rusckowski, Mary] Univ Massachusetts, Dept Radiol, Coll Med, Div Nucl Med, Worcester, MA 01605 USA. [Tampe, Bjoern; Tampe, Desiree; Zeisberg, Michael] Univ Gottingen, Goettingen Univ Med Ctr, Dept Nephrol & Rheumatol, D-37073 Gottingen, Germany. [Kalluri, Raghu] Harvard Massachusetts Inst Technol Div Hlth Sci &, Boston, MA USA. [Kalluri, Raghu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Sugimoto, H (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA. EM rkalluri@mdanderson.org RI LeBleu, Valerie /E-2991-2015 NR 15 TC 2 Z9 2 U1 0 U2 5 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 JUL PY 2013 VL 19 IS 7 BP 810 EP 811 DI 10.1038/nm.3081 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 179YB UT WOS:000321557700014 PM 23836214 ER PT J AU Mayers, JR Vander Heiden, MG AF Mayers, Jared R. Vander Heiden, Matthew G. TI BCAT1 defines gliomas by IDH status SO NATURE MEDICINE LA English DT Editorial Material ID CANCER; CELLS C1 [Mayers, Jared R.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Mayers, Jared R.; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayers, JR (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu OI Mayers, Jared/0000-0002-8607-1787 NR 12 TC 7 Z9 7 U1 1 U2 11 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 JUL PY 2013 VL 19 IS 7 BP 816 EP 817 DI 10.1038/nm.3263 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 179YB UT WOS:000321557700021 PM 23836221 ER PT J AU Daley, GQ Pasque, V Plath, K AF Daley, George Q. Pasque, Vincent Plath, Kathrin TI A new route to human embryonic stem cells SO NATURE MEDICINE LA English DT Editorial Material ID NUCLEAR TRANSFER C1 [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA USA. [Pasque, Vincent; Plath, Kathrin] Univ Calif Los Angeles, David Geffen Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Inst Mol Biol,Jonsson Comprehens Canc Ctr,Dept Bi, Los Angeles, CA 90095 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. OI Pasque, Vincent/0000-0002-5129-0146; Plath, Kathrin/0000-0001-7796-3372 NR 10 TC 0 Z9 0 U1 1 U2 12 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 JUL PY 2013 VL 19 IS 7 BP 820 EP 821 DI 10.1038/nm.3266 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 179YB UT WOS:000321557700023 ER PT J AU Buckner, RL Krienen, FM Yeo, BTT AF Buckner, Randy L. Krienen, Fenna M. Yeo, B. T. Thomas TI Opportunities and limitations of intrinsic functional connectivity MRI SO NATURE NEUROSCIENCE LA English DT Review ID RESTING-STATE NETWORKS; GLOBAL SIGNAL REGRESSION; DEFAULT MODE NETWORK; HUMAN BRAIN; STRUCTURAL CONNECTIVITY; CORPUS-CALLOSUM; CORTEX; ORGANIZATION; ARCHITECTURE; DISTINCT AB Intrinsic functional connectivity magnetic resonance imaging (fcMRI) has emerged as a powerful tool for mapping large-scale networks in the human brain. Robust and reliable functionally coupled networks can be detected in individuals that echo many known features of anatomical organization. Features of brain organization have been discovered, including descriptions of distributed large-scale networks interwoven throughout association cortex, interactions (including anticorrelations) between brain networks and insights into the topography of subcortical structures. But interpreting fcMRI is complicated by several factors. Functional coupling changes dynamically, suggesting that it is constrained by, but not fully dictated by, anatomic connectivity. Critically to study of between-group differences, fcMRI is sensitive to head motion and to differences in the mental states of participants during the scans. We discuss the potential of fcMRI in the context of its limitations. C1 [Buckner, Randy L.; Krienen, Fenna M.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.; Krienen, Fenna M.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yeo, B. T. Thomas] Duke NUS Grad Med Sch, Ctr Cognit Neurosci, Singapore, Singapore. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, Ctr Brain Sci, 33 Kirkland St, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu OI Yeo, B.T. Thomas/0000-0002-0119-3276 NR 58 TC 191 Z9 195 U1 6 U2 97 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2013 VL 16 IS 7 BP 832 EP 837 DI 10.1038/nn.3423 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 174UM UT WOS:000321180900013 PM 23799476 ER PT J AU Bradshaw, EM Chibnik, LB Keenan, BT Ottoboni, L Raj, T Tang, A Rosenkrantz, LL Imboywa, S Lee, M Von Korff, A Morris, MC Evans, DA Johnson, K Sperling, RA Schneider, JA Bennett, DA De Jager, PL AF Bradshaw, Elizabeth M. Chibnik, Lori B. Keenan, Brendan T. Ottoboni, Linda Raj, Towfique Tang, Anna Rosenkrantz, Laura L. Imboywa, Selina Lee, Michelle Von Korff, Alina Morris, Martha C. Evans, Denis A. Johnson, Keith Sperling, Reisa A. Schneider, Julie A. Bennett, David A. De Jager, Philip L. CA Alzheimer's Dis Neuroimaging Initi TI CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology SO NATURE NEUROSCIENCE LA English DT Article ID GENOME-WIDE ASSOCIATION; PITTSBURGH COMPOUND-B; COGNITIVE IMPAIRMENT; CEREBRAL INFARCTIONS; IDENTIFIES VARIANTS; COMMON VARIANTS; PET; DEMENTIA; EPHA1; PATHOLOGY AB In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes ( t(50) = 10.06, P-joint = 1.3 x 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-beta 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia. C1 [Bradshaw, Elizabeth M.; Chibnik, Lori B.; Keenan, Brendan T.; Ottoboni, Linda; Raj, Towfique; Tang, Anna; Rosenkrantz, Laura L.; Imboywa, Selina; Lee, Michelle; Von Korff, Alina; De Jager, Philip L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Bradshaw, Elizabeth M.; Chibnik, Lori B.; Keenan, Brendan T.; Ottoboni, Linda; Raj, Towfique; Tang, Anna; Rosenkrantz, Laura L.; Imboywa, Selina; Lee, Michelle; Von Korff, Alina; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Inst Neurosci, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Bradshaw, Elizabeth M.; Chibnik, Lori B.; Ottoboni, Linda; Raj, Towfique; Johnson, Keith; Sperling, Reisa A.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA USA. [Bradshaw, Elizabeth M.; Chibnik, Lori B.; Keenan, Brendan T.; Ottoboni, Linda; Raj, Towfique; Tang, Anna; Rosenkrantz, Laura L.; Imboywa, Selina; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Morris, Martha C.; Schneider, Julie A.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Chicago, IL 60612 USA. [Johnson, Keith; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimers Res & Treatment, Boston, MA 02115 USA. [Johnson, Keith; Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP De Jager, PL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. EM pdejager@partners.org RI Kowall, Neil/G-6364-2012; Saykin, Andrew/A-1318-2007; OI Kowall, Neil/0000-0002-6624-0213; Saykin, Andrew/0000-0002-1376-8532; OTTOBONI, LINDA/0000-0001-5412-7785; Preda, Adrian /0000-0003-3373-2438 FU US National Institutes of Health [R01 AG031553, R01 AG30146, R01 AG17917, R01 AG15819, P30 AG10161, R01 AG11101]; Illinois Department of Public Health; JDRF; American Diabetes Association; Boston Area Diabetes and Endocrinology Research Center; Harvard NeuroDiscovery Center; [R01 NS067305]; [RC2 GM093080]; [R01 AG043617] FX The authors are grateful to the participants of the ROS, MAP, CHAP, Harvard Aging Brain Study (HAB) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. Data used in preparation of this article were obtained from the ADNI database (http://adni.loni.ucla.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. We also thank the participants of the Brigham and Women's PhenoGenetic Project. This work is supported by the US National Institutes of Health (grants R01 AG031553, R01 AG30146, R01 AG17917, R01 AG15819, P30 AG10161 and R01 AG11101) and the Illinois Department of Public Health. This work was supported by grants R01 NS067305, RC2 GM093080 and R01 AG043617. E.M.B. receives support from the JDRF, American Diabetes Association, Boston Area Diabetes and Endocrinology Research Center and the Harvard NeuroDiscovery Center. NR 41 TC 124 Z9 126 U1 2 U2 37 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2013 VL 16 IS 7 BP 848 EP U92 DI 10.1038/nn.3435 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 174UM UT WOS:000321180900016 PM 23708142 ER PT J AU Roberson, DP Gudes, S Sprague, JM Patoski, HAW Robson, VK Blasl, F Duan, B Oh, SB Bean, BP Ma, QF Binshtok, AM Woolf, CJ AF Roberson, David P. Gudes, Sagi Sprague, Jared M. Patoski, Haley A. W. Robson, Victoria K. Blasl, Felix Duan, Bo Oh, Seog Bae Bean, Bruce P. Ma, Qiufu Binshtok, Alexander M. Woolf, Clifford J. TI Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons SO NATURE NEUROSCIENCE LA English DT Article ID SODIUM-CHANNEL BLOCKERS; DRY SKIN ITCH; BEHAVIORAL-RESPONSES; PAR-2 AGONIST; HISTAMINE H1; SPINAL-CORD; NOCICEPTORS; RECEPTOR; MICE; MOUSE AB The peripheral terminals of primary sensory neurons detect histamine and non-histamine itch-provoking ligands through molecularly distinct transduction mechanisms. It remains unclear, however, whether these distinct pruritogens activate the same or different afferent fibers. Using a strategy of reversibly silencing specific subsets of murine pruritogen-sensitive sensory axons by targeted delivery of a charged sodium-channel blocker, we found that functional blockade of histamine itch did not affect the itch evoked by chloroquine or SLIGRL-NH2, and vice versa. Notably, blocking itch-generating fibers did not reduce pain-associated behavior. However, silencing TRPV1(+) or TRPA1(+) neurons allowed allyl isothiocyanate or capsaicin, respectively, to evoke itch, implying that certain peripheral afferents may normally indirectly inhibit algogens from eliciting itch. These findings support the presence of functionally distinct sets of itch-generating neurons and suggest that targeted silencing of activated sensory fibers may represent a clinically useful anti-pruritic therapeutic approach for histaminergic and non-histaminergic pruritus. C1 [Roberson, David P.; Sprague, Jared M.; Patoski, Haley A. W.; Robson, Victoria K.; Oh, Seog Bae; Woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Roberson, David P.; Sprague, Jared M.; Patoski, Haley A. W.; Robson, Victoria K.; Oh, Seog Bae; Woolf, Clifford J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Roberson, David P.; Duan, Bo; Bean, Bruce P.; Ma, Qiufu; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Gudes, Sagi; Blasl, Felix; Binshtok, Alexander M.] Hebrew Univ Jerusalem, Fac Med, Inst Med Res Israel Canada, Dept Med Neurobiol, Jerusalem, Israel. [Gudes, Sagi; Binshtok, Alexander M.] Hebrew Univ Jerusalem, Edmond & Lily Safra Ctr Brain Sci, Jerusalem, Israel. [Sprague, Jared M.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Duan, Bo; Ma, Qiufu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oh, Seog Bae] Seoul Natl Univ, Natl Res Lab Pain, Dent Res Inst, Seoul, South Korea. [Oh, Seog Bae] Seoul Natl Univ, Sch Dent, Dept Neurobiol & Physiol, Seoul, South Korea. RP Binshtok, AM (reprint author), Hebrew Univ Jerusalem, Fac Med, Inst Med Res Israel Canada, Dept Med Neurobiol, Jerusalem, Israel. EM alexanderb@ekmd.huji.ac.il; clifford.woolf@childrens.harvard.edu FU US National Institutes of Health [NS072040, NS047710]; Ruth L Kirschstein National Research Service Award from the National Institute of Dental and Craniofacial Research FX We thank N. Ghasemlou and S. Ross for discussion and O. Viramontes for technical assistance. This study was supported by the US National Institutes of Health (NS072040 to B.P.B., Q.M., B.D. and C.J.W.; NS047710 to B.D. and Q.M.). J.M.S. is a recipient of a Ruth L Kirschstein National Research Service Award from the National Institute of Dental and Craniofacial Research. NR 46 TC 46 Z9 46 U1 2 U2 36 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2013 VL 16 IS 7 BP 910 EP U176 DI 10.1038/nn.3404 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 174UM UT WOS:000321180900025 PM 23685721 ER PT J AU Walker, BD Yu, XG AF Walker, Bruce D. Yu, Xu G. TI Unravelling the mechanisms of durable control of HIV-1 SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; HLA CLASS-I; NATURAL-KILLER-CELLS; HLA-B-ASTERISK-57(+) ELITE SUPPRESSORS; LONG-TERM NONPROGRESSORS; LOW-LEVEL VIREMIA; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; DENDRITIC CELLS AB Untreated HIV-1 infection typically progresses to AIDS within 10 years, but less than 1% of infected individuals remain healthy and have normal CD4(+) T cell counts and undetectable viral loads; some individuals have remained this way for 35 years and counting. Through a combination of large population studies of cohorts of these 'HIV-1 controllers' and detailed studies of individual patients, a heterogeneous picture has emerged regarding the basis for this remarkable resistance to AIDS progression. In this Review, we highlight the host genetic factors, the viral genetic factors and the immunological factors that are associated with the controller phenotype, we discuss emerging methodological approaches that could facilitate a better understanding of spontaneous HIV-1 immune control in the future, and we delineate implications for a 'functional cure' of HIV-1 infection. C1 [Walker, Bruce D.; Yu, Xu G.] Massachusetts Gen Hosp, Ragon Inst MGH & Harvard, Cambridge, MA 02139 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH & Harvard, Cambridge, MA 02139 USA. EM bwalker@partners.org FU US National Institutes of Health [AI098484, AI078799, AI089339, AI30914, AI67073]; Bill and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation; Phillip T. and Susan M. Ragon Foundation FX B.D.W. and X.G.Y. are supported by: the US National Institutes of Health grants AI098484, AI078799 and AI089339 (to X.G.Y.) as well as AI30914 and AI67073 (to B. D. W.); the Bill and Melinda Gates Foundation; the Mark and Lisa Schwartz Foundation; and the Phillip T. and Susan M. Ragon Foundation. NR 139 TC 65 Z9 67 U1 6 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUL PY 2013 VL 13 IS 7 BP 487 EP 498 DI 10.1038/nri3478 PG 12 WC Immunology SC Immunology GA 170LT UT WOS:000320853100009 PM 23797064 ER PT J AU Langbaum, JB Fleisher, AS Chen, KW Ayutyanont, N Lopera, F Quiroz, YT Caselli, RJ Tariot, PN Reiman, EM AF Langbaum, Jessica B. Fleisher, Adam S. Chen, Kewei Ayutyanont, Napatkamon Lopera, Francisco Quiroz, Yakeel T. Caselli, Richard J. Tariot, Pierre N. Reiman, Eric M. TI Ushering in the study and treatment of preclinical Alzheimer disease SO NATURE REVIEWS NEUROLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; APOLIPOPROTEIN-E EPSILON-4; PITTSBURGH COMPOUND-B; CEREBROSPINAL-FLUID MARKERS; AMYLOID-BETA DEPOSITION; RESTING-STATE NETWORKS; HEALTHY OLDER-ADULTS; BRAIN ATROPHY RATES; FLORBETAPIR F 18 AB Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of, or completely prevent clinical decline. In this Review, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how advances in the field have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research. C1 [Langbaum, Jessica B.; Fleisher, Adam S.; Chen, Kewei; Ayutyanont, Napatkamon; Tariot, Pierre N.; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ 85006 USA. [Lopera, Francisco] Univ Antioquia, Grp Neurociencias Antioquia, Medellin, Colombia. [Quiroz, Yakeel T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Caselli, Richard J.] Mayo Clin Arizona, Dept Neurol, Scottsdale, AZ 85259 USA. RP Reiman, EM (reprint author), Banner Alzheimers Inst, 901 East Willetta St, Phoenix, AZ 85006 USA. EM eric.reiman@bannerhealth.com RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU National Institute on Aging [R01AG031581, P30AG19610, RF1AG041705]; National Institute of Neurological Disorders and Stroke [F31-NS078786]; Colciencias [1115-493-26133, 1115-545-31651, 1115-519-29028]; Banner Alzheimer's Foundation; state of Arizona; Geoffrey Benne Gives Back Alzheimer's Initiative; Nomis Foundations FX This article was supported by grants from the National Institute on Aging (R01AG031581 and P30AG19610 to E.M. Reiman, and RF1AG041705 to E.M. Reiman, P.N. Tariot and F. Lopera), the National Institute of Neurological Disorders and Stroke (F31-NS078786 to Y.T. Quiroz), Colciencias (1115-493-26133, 1115-545-31651 and 1115-519-29028 to F. Lopera), the Banner Alzheimer's Foundation, and the state of Arizona. The authors acknowledge research support from the Geoffrey Benne Gives Back Alzheimer's Initiative (to J.B. Langbaum), the Anonymous Foundation (to E. M. Reiman) and the Nomis Foundations (to P.N. Tariot, F. Lopera and E. M. Reiman). We thank H. Protas for her assistance in creating the figures prior to submission, and N. Fox, C. Rowe, M. Weiner and their colleagues for permission to use their images in Figure 2. We thank our valued research participants for their invaluable dedication and inspiration. NR 172 TC 50 Z9 52 U1 5 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUL PY 2013 VL 9 IS 7 BP 371 EP 381 DI 10.1038/nrneurol.2013.107 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 176VX UT WOS:000321335300007 PM 23752908 ER PT J AU Lafata, JE Morris, HL Dobie, E Heisler, M Werner, RM Dumenci, L AF Lafata, Jennifer Elston Morris, Heather L. Dobie, Elizabeth Heisler, Michele Werner, Rachel M. Dumenci, Levent TI Patient-reported use of collaborative goal setting and glycemic control among patients with diabetes SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes; Collaborative goal setting; Glycemic control; Perceived competency; Patient-clinician communication ID COMPLEX DECISION-MAKING; CHRONIC CARE MODEL; QUALITY-OF-LIFE; SELF-MANAGEMENT; ACTIVATION INTERVENTION; PHYSICIAN COMMUNICATION; METABOLIC CONTROL; HEALTH; PERFORMANCE; STANDARDS AB Objective: Little is known about how patient-clinician communication leads to better outcomes. Among patients with diabetes, we describe patient-reported use of collaborative goal setting and evaluate whether perceived competency and physician trust mediate the association between collaborative goal setting and glycemic control. Methods: Data from a patient survey administered in 2008 to a cohort of insured patients aged 18+ years with diabetes who initiated oral mono-therapy between 2000 and 2005 were joined with pharmaceutical claims data for the prior 12 months and laboratory data for the prior and subsequent 12 months (N = 1065). A structural equation model (SEM) was used to test mediation models controlling for baseline HbA1c. Results: The hypothesized mediation model was supported. Patient-reported use of more collaborative goal setting was associated with greater perceived self-management competency and increased level of trust in the physician (p < 0.05). In turn, both greater perceived competence and increased trust were associated with increased control (p < 0.05). Conclusions: Findings indicate that engaging patients in collaborative goal setting during clinical encounters has potential to foster a trusting patient-clinician relationship as well as enhance patient perceived competence, thereby improving clinical control. Practice implications: Fostering collaborative goal setting may yield payoffs in improved clinical outcomes among patients with diabetes. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Lafata, Jennifer Elston; Morris, Heather L.; Dumenci, Levent] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA. [Dobie, Elizabeth] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA. [Heisler, Michele] Univ Michigan, Ann Arbor, MI 48109 USA. [Werner, Rachel M.] Univ Penn, Dept Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Lafata, JE (reprint author), 830 E Main Floor,9th Floor,POB 980149, Richmond, VA 23298 USA. EM jelstonlafat@vcu.edu RI Heisler, Michele/B-5774-2015 OI Heisler, Michele/0000-0002-6889-2063 FU Sanofi-Aventis FX The database used was developed under a contract from Sanofi-Aventis. NR 34 TC 5 Z9 5 U1 3 U2 12 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 JUL PY 2013 VL 92 IS 1 BP 94 EP 99 DI 10.1016/j.pec.2013.01.016 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 178YQ UT WOS:000321483700014 PM 23433777 ER PT J AU Jung, M Ramanadhan, S Viswanath, K AF Jung, Minsoo Ramanadhan, Shoba Viswanath, Kasisomayajula TI Effect of information seeking and avoidance behavior on self-rated health status among cancer survivors SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Cancer; Self-rated health; Health communication; Communication inequalities; Health information seeking behavior; Health information avoidance behavior ID QUALITY-OF-LIFE; BREAST-CANCER; PROSTATE-CANCER; DETERMINANTS; POPULATION; MORTALITY; OUTCOMES; WOMEN AB Objective: Social determinants, such as socioeconomic status (SES) and race/ethnicity are linked to striking health disparities across the cancer continuum. One important mechanism linking social determinants and health disparities may be communication inequalities that are caused by differences in accessing, processing and utilizing cancer information. In this context, we examined health information-seeking/avoidance as a potential mediator between social determinants and self-rated health (SRH) status among cancer survivors. Methods: Data came from the 2008 well-informed, thriving and surviving (WITS) study of post-treatment cancer survivors (n = 501). We examined the mediating effect of health communication-related behavior between SES and disparities in SRH. Results: The likelihood of belonging to the Low SRH group was higher among patients who had avoided health information and whose family members had not sought health information on behalf of the survivor, those in the lowest household income bracket, and those who had high school or less education after adjusting for potential confounders. Conclusion: Differences in SRH among cancer survivors are associated with SES as well as communication inequalities. Practice implications: It is necessary to provide a supportive environment in which health information is made available if disparities in health-related quality of life among cancer survivors are to be reduced. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Jung, Minsoo; Ramanadhan, Shoba; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. RP Jung, M (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 450 Brookline Ave,LW601, Boston, MA 02215 USA. EM minsoo_jung@dfci.harvard.edu OI Jung, Minsoo/0000-0003-3317-6507 NR 40 TC 9 Z9 9 U1 4 U2 21 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 JUL PY 2013 VL 92 IS 1 BP 100 EP 106 DI 10.1016/j.pec.2013.02.008 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 178YQ UT WOS:000321483700015 PM 23523194 ER PT J AU Shahim, P Darin, N Andreasson, U Blennow, K Jennions, E Lundgren, J Mansson, JE Naess, K Tornhage, CJ Zetterberg, H Mattsson, N AF Shahim, Pashtun Darin, Niklas Andreasson, Ulf Blennow, Kaj Jennions, Elizabeth Lundgren, Johan Mansson, Jan-Eric Naess, Karin Tornhage, Carl-Johan Zetterberg, Henrik Mattsson, Nildas TI Cerebrospinal Fluid Brain Injury Biomarkers in Children: A Multicenter Study SO PEDIATRIC NEUROLOGY LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; ALZHEIMERS-DISEASE; NEUROFILAMENT PROTEIN; STATUS EPILEPTICUS; TAU-PROTEIN; MARKERS; NEUROBORRELIOSIS; HYDROCEPHALUS; MENINGITIS; ASTROCYTES AB BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflecting neuronal and astroglial injury, such as total tau (T-tau), glial flbrillary acidic protein (GFAP), and neurofilament light (NFL), have been extensively investigated in neurologic diseases in adults, but no large study has investigated these biomarkers in children. METHODS: This study presents a detailed evaluation of CFS T-tau, GFAP, NFL, and CSF:albumin ratio in a large cohort of pediatric patients. This is a retrospective multicenter study on pediatric patients aged <16 years (n = 607), where neuronal injury biomarkers T-tau, GFAP, NFL, and CSF albumin ratio were analyzed during 2000-2010 at the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Sweden. The patients were grouped into eight categories: epilepsy, infectious and inflammatory central nervous system disorders, progressive encephalopathy, static encephalopathy, tumors, movement disorders, miscellaneous disorders, and a control group. RESULTS: T-tau, GFAP, and NFL were increased in progressive encephalopathy (P < 0.001), epilepsy (P < 0.001), and infectious and inflammatory central nervous system disorders (P < 0.001) compared with controls. T-tau was the biomarker with the highest diagnostic accuracy with the area under the curve of 0.83 (95% confidence interval (CI), 0.77-0.90; P < 0.0001) for progressive encephalopathy followed by epilepsy 0.80 (95% CI, 0.75-0.87; P < 0.0001). The combination of all four biomarkers further improved the area under the curve for the progressive encephalopathy 0.87 (95% CI, 0.77-0.89; P < 0.0001), followed by epilepsy 0.81 (95% CI, 0.74-0.80; P = 0.030). The combination of the biomarkers also separated progressive from static encephalopathy 0.88 (95% CI, 0.83-0.93; P < 0.0001). CONCLUSIONS: CSF T-tau, GFAP, and NFL are differently altered across different neurologic diseases in children. Importantly, the biomarker pattern distinguishes between progressive and static neurologic disorders. (c) 2013 Elsevier Inc. All rights reserved. C1 [Shahim, Pashtun; Andreasson, Ulf; Blennow, Kaj; Mansson, Jan-Eric; Zetterberg, Henrik; Mattsson, Nildas] Sahlgrenska Univ Hosp Molndal, Inst Neurosci & Physiol, Dept Neurochem, Clin Neurochem Lab, S-43180 Molndal, Sweden. [Zetterberg, Henrik] UCL Inst Neurol, London, England. [Darin, Niklas] Sahlgrens Univ Hosp, Queen Silvia Childrens Hosp, Inst Clin Sci, Dept Pediat, Ostra, Sweden. [Jennions, Elizabeth] Sodra Alvborgs Hosp, Boras, Sweden. [Lundgren, Johan] Skane Univ Hosp, Dept Clin Sci, Pediat Unit, Lund, Sweden. [Naess, Karin] Karolinska Univ Hosp, Ctr Inherited Metab Dis, Stockholm, Sweden. [Naess, Karin] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Tornhage, Carl-Johan] Skaraborgs Hosp, Dept Pediat, Skovde, Sweden. [Mattsson, Nildas] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA. RP Shahim, P (reprint author), Sahlgrenska Univ Hosp Molndal, Clin Neurochem Lab, S-43180 Molndal, Sweden. EM pashtun.shahim@neuro.gu.se FU Swedish Research Council; Alzheimer's Association; Swedish Brain Power; Swedish State Support for Clinical Research; Sahlgrenska University Hospital; Sahlgrenska Academy; Lundbeck Foundation; Stiftelsen Psykiatriska Forskningsfonden; Stiftelsen Gamla Tjanarinnor; Uppsala Universitets Medicinska Fakultet stiftelse for psykiatrisk och neurologisk forskning; Swedish Brain Fund; Goteborgs lakaresallskap; Thureus stiftelse; Pfannenstills stiftelse; Demensfonden, Sweden FX The authors' work is supported by grants from the Swedish Research Council, Alzheimer's Association, Swedish Brain Power, Swedish State Support for Clinical Research, Sahlgrenska University Hospital, Sahlgrenska Academy, the Lundbeck Foundation, Stiftelsen Psykiatriska Forskningsfonden, Stiftelsen Gamla Tjanarinnor, Uppsala Universitets Medicinska Fakultet stiftelse for psykiatrisk och neurologisk forskning, the Swedish Brain Fund, Goteborgs lakaresallskap, Thureus stiftelse, Pfannenstills stiftelse, and Demensfonden, Sweden. NR 37 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JUL PY 2013 VL 49 IS 1 BP 31 EP 39 DI 10.1016/j.pediatrneurol.2013.02.015 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 183IR UT WOS:000321808700007 PM 23827424 ER PT J AU Waugh, JL AF Waugh, Jeff L. TI Acute Dyskinetic Reaction in a Healthy Toddler Following Methylphenidate Ingestion SO PEDIATRIC NEUROLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POSTNATAL-DEVELOPMENT; CHILDREN; RECEPTORS; DYSTONIA; CORTEX AB BACKGROUND: Acute dyskinetic or dystonic reactions are a long-recognized complication of medications that alter dopamine signaling. Most reactions occur following exposure to agents that block dopamine receptors (e.g., neuroleptics). However, agents that increase dopaminergic transmission (such as methylphenidate) can also trigger acute dyskinesias. This has been previously reported only in patients also taking dopamine antagonists or, less commonly, in children with developmental abnormalities. CASE DESCRIPTION: The present report describes a previously healthy toddler who developed transient torticollis and orolingual dyskinesias following accidental exposure to methylphenidate. He had no preexisting movement disorder, central nervous system injury, or developmental abnormalities-in short, none of the previously reported risk factors for this side effect. HYPOTHESIS AND CONCLUSIONS: The unique features of this case led to the hypothesis that developmental shifts in dopamine signaling were the basis for his particular sensitivity to methylphenidate. If confirmed, this hypothesis has implications for the treatment of common childhood attentional and behavioral disorders. The article includes a literature review of dyskinetic/dystonic reactions in children and the developmental regulation of dopamine metabolism. (c) 2013 Elsevier Inc. All rights reserved. C1 [Waugh, Jeff L.] Boston Childrens Hosp, Boston, MA 02115 USA. RP Waugh, JL (reprint author), Massachusetts Gen Hosp, 55 Fruit Street,WAC 7, Boston, MA 02114 USA. EM jeff.waugh@childrens.harvard.edu OI Waugh, Jeff/0000-0001-7526-1342 NR 14 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JUL PY 2013 VL 49 IS 1 BP 58 EP 60 DI 10.1016/j.pediatrneurol.2013.01.008 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 183IR UT WOS:000321808700012 PM 23683540 ER PT J AU Kalish, BT Kieran, MW Puder, M Panigrahy, D AF Kalish, Brian T. Kieran, Mark W. Puder, Mark Panigrahy, Dipak TI The growing role of eicosanoids in tissue regeneration, repair, and wound healing SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE Regeneration; Wound healing; Repair; Organ growth ID ENDOTHELIAL GROWTH-FACTOR; COMPENSATORY LUNG GROWTH; NONSELECTIVE CYCLOOXYGENASE-2 INHIBITORS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OSTEOPENIC OVARIECTOMIZED RATS; ENDOGENOUS PROSTAGLANDIN E-2; CONTROLLED-RELEASE PELLETS; INDUCED PULMONARY-FIBROSIS; STEM-CELL PROLIFERATION; LIVER-REGENERATION AB Tissue repair and regendation are essential processes in maintaining tissue homeostasis, especially in response to injury or stress. Eicosanoids are ubiquitous mediators of cell proliferation, differentiation, and angiogenesis, all of which are important for tissue growth. Eicosanoids regulate the induction and resolution of inflammation that accompany the tissue response to injury. In this review, we describe how this diverse group of molecules is a key regulator of tissue repair and regeneration in multiple organ systems and biologic contexts. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kalish, Brian T.; Kieran, Mark W.; Puder, Mark; Panigrahy, Dipak] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. [Kalish, Brian T.; Puder, Mark] Harvard Univ, Sch Med, Dept Surg, Boston Childrens Hosp, Boston, MA 02115 USA. [Kieran, Mark W.; Panigrahy, Dipak] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Kalish, BT (reprint author), Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. EM brian.kalish@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU National Cancer Institute [RO1CA148633-O3, RO1 CA170549-01]; Stop and Shop Pediatric Brain Tumor Fund; C.J. Buckley Pediatric Brain Tumor Fund FX This work was supported by National Cancer Institute grant RO1CA148633-O3 and RO1 CA170549-01(DP); Stop and Shop Pediatric Brain Tumor Fund and the C.J. Buckley Pediatric Brain Tumor Fund (to MWK). NR 156 TC 12 Z9 12 U1 2 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JUL-AUG PY 2013 VL 104 SI SI BP 130 EP 138 DI 10.1016/j.prostaglandins.2013.05.002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183GM UT WOS:000321802500016 PM 23727457 ER PT J AU Goske, MJ Strauss, KJ Coombs, LP Mandel, KE Towbin, AJ Larson, DB Callahan, MJ Darge, K Podberesky, DJ Frush, DP Westra, SJ Prince, JS AF Goske, Marilyn J. Strauss, Keith J. Coombs, Laura P. Mandel, Keith E. Towbin, Alexander J. Larson, David B. Callahan, Michael J. Darge, Kassa Podberesky, Daniel J. Frush, Donald P. Westra, Sjirk J. Prince, Jeffrey S. TI Diagnostic Reference Ranges for Pediatric Abdominal CT SO RADIOLOGY LA English DT Article ID RADIATION-DOSE REDUCTION; COMPUTED-TOMOGRAPHY; EXPOSURE; RISK; AGE AB Purpose: To develop diagnostic reference ranges (DRRs) and a method for an individual practice to calculate site-specific reference doses for computed tomographic (CT) scans of the abdomen or abdomen and pelvis in children on the basis of body width (BW). Materials and Methods: This HIPAA-compliant multicenter retrospective study was approved by institutional review boards of participating institutions; informed consent was waived. In 939 pediatric patients, CT doses were reviewed in 499 (53%) male and 440 (47%) female patients (mean age, 10 years). Doses were from 954 scans obtained from September 1 to December 1, 2009, through Quality Improvement Registry for CT Scans in Children within the National Radiology Data Registry, American College of Radiology. Size-specific dose estimate (SSDE), a dose estimate based on BW, CT dose index, dose-length product, and effective dose were analyzed. BW measurement was obtained with electronic calipers from the axial image at the splenic vein level after completion of the CT scan. An adult-sized patient was defined as a patient with BW of 34 cm. An appropriate dose range for each DRR was developed by reviewing image quality on a subset of CT scans through comparison with a five-point visual reference scale with increments of added simulated quantum mottle and by determining DRR to establish lower and upper bounds for each range. Results: For 954 scans, DRRs (SSDEs) were 5.8-12.0, 7.3-12.2, 7.6-13.4, 9.8-16.4, and 13.1-19.0 mGy for BWs less than 15, 15-19, 20-24, 25-29, and 30 cm or greater, respectively. The fractions of adult doses, adult SSDEs, used within the consortium for patients with BWs of 10, 14, 18, 22, 26, and 30 cm were 0.4, 0.5, 0.6, 0.7, 0.8, and 0.9, respectively. Conclusion: The concept of DRRs addresses the balance between the patient's risk (radiation dose) and benefit (diagnostic image quality). Calculation of reference doses as a function of BW for an individual practice provides a tool to help develop site-specific CT protocols that help manage pediatric patient radiation doses. (C) RSNA, 2013 C1 [Goske, Marilyn J.; Strauss, Keith J.; Towbin, Alexander J.; Larson, David B.; Podberesky, Daniel J.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. [Mandel, Keith E.] Cincinnati Childrens Hosp Med Ctr, James M Anderson Ctr Healthcare Syst Excellence, Cincinnati, OH 45229 USA. [Mandel, Keith E.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Coombs, Laura P.] Amer Coll Radiol, Natl Radiol Data Registry, Reston, VA USA. [Callahan, Michael J.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Darge, Kassa] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Frush, Donald P.] Duke Univ, Med Ctr, Div Pediat Radiol, Durham, NC USA. [Westra, Sjirk J.] Massachusetts Gen Hosp, Sect Pediat Radiol, Boston, MA 02114 USA. [Prince, Jeffrey S.] Primary Childrens Med Ctr, Dept Radiol, Salt Lake City, UT USA. RP Goske, MJ (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Radiol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM marilyn.goske@cchmc.org RI Frush, Donald/M-6457-2015; OI Frush, Donald/0000-0002-6928-4465; Towbin, Alexander/0000-0003-1729-5071 FU Toshiba FX M.J.G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received payment for three to six visiting professorships a year at academic institutions. Other relationships: none to disclose. K.J.S. No relevant conflicts of interest to disclose. L. P. C. No relevant conflicts of interest to disclose. K. E. M. No relevant conflicts of interest to disclose. A.J.T. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received royalties for a book from Amirsys; holds stock in and was paid for travel, accommodations, and meeting expenses unrelated to activities listed from Merge Healthcare. Other relationships: none to disclose. D. B. L. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author and institution were paid for patents through intellectual property license agreement by Radimetrics. Other relationships: none to disclose. M.J.C. No relevant conflicts of interest to disclose. K. D. No relevant conflicts of interest to disclose. D.J.P. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received travel reimbursement for user group meeting by GE Healthcare and Philips, received payment for service on professional speakers bureau from Toshiba, received royalties for textbook chapter from Amirsys. Other relationships: none to disclose. D. P. F. No relevant conflicts of interest to disclose. S.J.W. No relevant conflicts of interest to disclose. J.S.P. No relevant conflicts of interest to disclose. NR 31 TC 38 Z9 38 U1 1 U2 13 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2013 VL 268 IS 1 BP 208 EP 218 DI 10.1148/radiol.13120730 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169ER UT WOS:000320761400023 PM 23513245 ER PT J AU Ackman, JB Kovacina, B Carter, BW Wu, CC Sharma, A Shepard, JAO Halpern, EF AF Ackman, Jeanne B. Kovacina, Bojan Carter, Brett W. Wu, Carol C. Sharma, Amita Shepard, Jo-Anne O. Halpern, Elkan F. TI Sex Difference in Normal Thymic Appearance in Adults 20-30 Years of Age SO RADIOLOGY LA English DT Article ID GLAND; TRANSPLANTATION; PREGNANCY AB Purpose: To determine whether there is a sex difference in the appearance of the normal thymus in 20-30-year-old men and women. Materials and Methods: This retrospective study was approved by the institutional review board and was compliant with HIPAA. The requirement for informed consent was waived. Images and medical records of 238 consecutive subjects without known thymic disease (175 men, 63 women) who underwent chest computed tomography with intravenous contrast material in 2008 were reviewed. Average thymic region of interest (ROI), subjective assessment of thymic attenuation by using a scale of grades 0-3, thymic anteroposterior measurement, and mean maximal thymic lobe thickness were recorded by two independent thoracic radiologists, blinded to subject age and sex. Thymic morphologic characteristics were assessed in consensus. The two-sided Wilcoxon rank-sum test, Student t test, test for linear regression, analysis of covariance, two-way factorial analysis of variance, and continuity-adjusted chi(2) test were used for statistical analysis. Results: There was a significant sex difference in thymic attenuation as measured objectively by using mean thymic ROI measurement (P < .0001) and subjectively by using a scale of grades 0-3 (P,.0001), which held true when corrected for age (P,.0001). A sex difference was also found in regard to the rate of decrease in mean thymic attenuation with age, with men's thymuses exhibiting a significant decrease in attenuation during the decade, unlike women (P = .0479). There was no significant sex difference in mean maximal thymic lobe thickness (P = .8697). A quadrilateral, as opposed to triangular, configuration of the thymus was more common in women than men (P = .0034). Conclusion: There is a significant sex difference in normal thymic appearance in 20-30-year-old men and women. The thymus of 20-30-year-old women typically exhibits higher attenuation and more commonly exhibits a quadrilateral configuration. (C) RSNA, 2013 C1 [Ackman, Jeanne B.; Wu, Carol C.; Sharma, Amita; Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kovacina, Bojan] McGill Univ, Jewish Gen Hosp, Dept Radiol, Montreal, PQ H3T 1E2, Canada. [Carter, Brett W.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Ackman, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders House 202, Boston, MA 02114 USA. EM jackman@partners.org FU CRICO FX J.B.A. No relevant conflicts of interest to disclose. B. K. No relevant conflicts of interest to disclose. B. W. C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received royalties from Amirsys. Other relationships: none to disclose. C. C. W. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received royalties from Amirsys. Other relationships: none to disclose. A. S. No relevant conflicts of interest to disclose. J.O.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: was paid for expert testimony by CRICO. Other relationships: none to disclose. E. F. H. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: paid for consultancy by Hologic and for expert testimony by Ameritox and received travel, accommodations, and meeting expenses by RSNA. Other relationships: none to disclose. NR 16 TC 12 Z9 12 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2013 VL 268 IS 1 BP 245 EP 253 DI 10.1148/radiol.13121104 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169ER UT WOS:000320761400027 PM 23440318 ER PT J AU Maurovich-Horvat, P Schlett, CL Hoffmann, U AF Maurovich-Horvat, Pal Schlett, Christopher L. Hoffmann, Udo TI Diagnostic Accuracy of CT Angiography, Intravascular US, and Optical Frequency Domain Imaging in the Differentiation of Advanced Coronary Plaques Response SO RADIOLOGY LA English DT Letter C1 [Maurovich-Horvat, Pal] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Maurovich-Horvat, Pal] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Maurovich-Horvat, Pal; Schlett, Christopher L.; Hoffmann, Udo] Semmelweis Univ, Heart & Vasc Ctr, H-1085 Budapest, Hungary. RP Maurovich-Horvat, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X NR 3 TC 0 Z9 0 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2013 VL 268 IS 1 BP 304 EP 305 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169ER UT WOS:000320761400036 PM 23951582 ER PT J AU Kulkarni, NM Pinho, DF Kambadakone, AR Sahani, DV AF Kulkarni, Naveen M. Pinho, Daniella F. Kambadakone, Avinash R. Sahani, Dushyant V. TI Emerging Technologies in CT-Radiation Dose Reduction and Dual-Energy CT SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID STATISTICAL ITERATIVE RECONSTRUCTION; MULTIDETECTOR-ROW CT; LOW TUBE VOLTAGE; HYPERVASCULAR LIVER-TUMORS; AUTOMATIC EXPOSURE CONTROL; IODINE OVERLAY TECHNIQUE; IMAGE-QUALITY; ABDOMINAL CT; COMPUTED-TOMOGRAPHY; RENAL MASSES C1 [Kulkarni, Naveen M.; Pinho, Daniella F.; Kambadakone, Avinash R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Massachusetts Gen Hosp, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 68 TC 12 Z9 12 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2013 VL 48 IS 3 BP 192 EP 202 DI 10.1053/j.ro.2013.03.007 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 180NQ UT WOS:000321602300003 PM 23796370 ER PT J AU Hodin, R Clark, O Doherty, G Grant, C Heller, K Weigel, R AF Hodin, Richard Clark, Orlo Doherty, Gerard Grant, Clive Heller, Keith Weigel, Ron TI Voice issues and laryngoscopy in thyroid surgery patients SO SURGERY LA English DT Editorial Material ID RECURRENT LARYNGEAL NERVE; RISK; INJURY C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Boston Univ, Dept Surg, Boston, MA 02215 USA. Mayo Clin, Dept Surg, Rochester, MN USA. NYU Langone Med Ctr, Dept Surg, New York, NY USA. Univ Iowa, Dept Surg, Iowa City, IA 52242 USA. RP Hodin, R (reprint author), 15 Parkman St, Boston, MA 02114 USA. EM rhodin@partners.org OI Doherty, Gerard/0000-0002-1685-9552; Heller, Keith/0000-0003-2836-3359 NR 12 TC 10 Z9 10 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2013 VL 154 IS 1 BP 46 EP 47 DI 10.1016/j.surg.2013.04.014 PG 2 WC Surgery SC Surgery GA 174PR UT WOS:000321168400008 PM 23809485 ER PT J AU Darkins, A Foster, L Anderson, C Goldschmidt, L Selvin, G AF Darkins, Adam Foster, Linda Anderson, Carla Goldschmidt, Leonard Selvin, Gerald TI The Design, Implementation, and Operational Management of a Comprehensive Quality Management Program to Support National Telehealth Networks SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telehealth; policy; business administration/economics ID TELEMENTAL HEALTH; HOME TELEHEALTH; OF-CARE AB The Veterans Health Administration (VHA) is a large integrated healthcare system with a mission to care for over 5.6 million Veteran patients annually. VHA, like other healthcare organizations, is challenged with providing access to care to those it serves when they live at a distance from a physical site of care. VHA has embraced telehealth as a way of delivering care at a distance and increase access to specialty care services. Since 2003 VHA has developed large national telehealth networks that provided care to 497,342 patients in fiscal year 2012, who received 1,429,424 episodes of care, and is recognized as a national leader in this field. To ensure the safety and effectiveness of its telehealth networks in their delivery of care VHA has implemented a dedicated quality management (QM) program for telehealth. QM data for telehealth are reviewed at 3-month intervals, and the procedures and processes in place to support telehealth in VHA are assessed biannually in an internal accreditation process called "Telehealth Conditions of Participation." This collegial, nonadversarial process has ensured that all designated telehealth programs meet minimal standards and disseminate best practice. As a result of VHA's QM program, telehealth services in VHA meet consistently high clinical outcomes and have received no adverse Joint Commission citations. The Joint Commission regularly assesses patients managed via telehealth under its tracer methodology reviews. C1 [Darkins, Adam] Telehlth Serv, Dept Vet Affairs, Washington, DC USA. [Foster, Linda] Telehlth Serv, Dept Vet Affairs, Indianapolis, IN USA. [Anderson, Carla] Telehlth Serv, Dept Vet Affairs, Bay Pines, FL USA. [Goldschmidt, Leonard] Palo Alto VA Med Ctr, Palo Alto, CA USA. [Selvin, Gerald] VA Boston Healthcare Syst, Boston, MA USA. RP Darkins, A (reprint author), Dept Vet Affairs, Off Care Coordinat, 810 Vermont Ave NW, Washington, DC 20420 USA. EM adam.darkins@va.gov NR 21 TC 6 Z9 6 U1 1 U2 7 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 JUL PY 2013 VL 19 IS 7 BP 557 EP 564 DI 10.1089/tmj.2012.0263 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 180CM UT WOS:000321570500011 PM 23705961 ER PT J AU Blackard, JT Kong, L Huber, AK Tomer, Y AF Blackard, Jason T. Kong, Ling Huber, Amanda K. Tomer, Yaron TI Hepatitis C Virus Infection of a Thyroid Cell Line: Implications for Pathogenesis of Hepatitis C Virus and Thyroiditis SO THYROID LA English DT Article ID INTERFERON-ALPHA THERAPY; BLOOD MONONUCLEAR-CELLS; HCV CHRONIC HEPATITIS; HUMAN HEPATOMA-CELLS; HUMAN HEPATOCYTES; IN-VITRO; EXTRAHEPATIC REPLICATION; ANTIVIRAL ACTION; WHOLE-BLOOD; INTERLEUKIN-8 AB Background: Autoimmune and non-autoimmune thyroiditis frequently occur in persons with hepatitis C virus (HCV) infection. Treatment with interferon alpha (IFN alpha) is also associated with significant risk for the development of thyroiditis. To explore HCV-thyroid interactions at a cellular level, we evaluated whether a human thyroid cell line (ML1) could be infected productively with HCV in vitro. Methods and Results: ML1 cells showed robust surface expression of the major HCV receptor CD81. Using a highly sensitive, strand-specific reverse transcription polymerase chain reaction assay, positive-sense and negative-sense HCV RNA were detected in ML1 cell lysates at days 3, 7, and 14 postinfection with HCV. HCV core protein was expressed at high levels in ML1 supernatants at days 1, 3, 5, 7, and 14 postinfection. The nonstructural protein NS5A was also detected in ML1 cell lysates by Western blotting. HCV entry into ML1 cells was shown to be dependent on the HCV entry factors CD81 and SR-B1/CLA1, while IFN alpha inhibited HCV replication in ML1 cells in a dose-dependent manner. Supernatants from HCV-infected ML1 cells were able to infect fresh ML1 cells productively, suggesting that infectious virions could be transferred from infected to naive thyroid cells in vivo. Additionally, HCV infection of ML1 cells led to increased expression of the proinflammatory cytokine IL-8. Conclusions: For the first time, we have demonstrated that HCV can infect human thyroid cells in vitro. These findings strongly suggest that HCV infection of thyrocytes may play a role in the association between chronic HCV infection and thyroid autoimmunity. Furthermore, the thyroid may serve as an extrahepatic reservoir for HCV viral replication, thus contributing to the persistence of viral infection and to the development of thyroid autoimmunity. C1 [Blackard, Jason T.; Kong, Ling] Univ Cincinnati, Coll Med, Div Digest Dis, Dept Internal Med, Cincinnati, OH 45267 USA. [Huber, Amanda K.; Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, New York, NY USA. RP Blackard, JT (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, Dept Internal Med, ML 0595,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM jason.blackard@uc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA Biomedical Laboratory Research and Development Merit Award; NIDDK [DK61659, DK67555, DK073681] FX This material is based on work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and by the VA Biomedical Laboratory Research and Development Merit Award and by grants DK61659, DK67555, and DK073681 from NIDDK (to Y.T.). The authors would like to thank Ms. Eleanor Powell for her critical evaluation of this manuscript. NR 51 TC 25 Z9 28 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 2013 VL 23 IS 7 BP 863 EP 870 DI 10.1089/thy.2012.0507 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179XF UT WOS:000321554900013 PM 23259732 ER PT J AU Salami, SS Schmidt, F Laxman, B Regan, MM Rickman, DS Scherr, D Bueti, G Siddiqui, J Tomlins, SA Wei, JT Chinnaiyan, AM Rubin, MA Sanda, MG AF Salami, Simpa S. Schmidt, Folke Laxman, Bharathi Regan, Meredith M. Rickman, David S. Scherr, Douglas Bueti, Gerardina Siddiqui, Javed Tomlins, Scott A. Wei, John T. Chinnaiyan, Arul M. Rubin, Mark A. Sanda, Martin G. TI Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Screening; DRE; Biomarkers; Cancer detection; Gene fusion ID DIGITAL RECTAL EXAMINATION; FUSION TRANSCRIPTS; SCREENING TRIAL; GENE FUSIONS; ASSAY; PERFORMANCE; MORTALITY; SEDIMENTS; ANTIGEN; BIOPSY AB Objectives: We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy. Materials and methods: Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at 2 centers; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed. Results: Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; P < 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared with 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity). Conclusions: A clinical algorithm specifying biopsy for all patients with PSA >= 10 ng/ml, while restricting biopsy among those with PSA <10 ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer. (C) 2013 Elsevier Inc. All rights reserved. C1 [Salami, Simpa S.; Bueti, Gerardina; Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02215 USA. [Salami, Simpa S.; Regan, Meredith M.; Sanda, Martin G.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Schmidt, Folke; Rickman, David S.; Scherr, Douglas; Rubin, Mark A.] Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. [Schmidt, Folke; Rickman, David S.; Scherr, Douglas; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol, New York, NY 10065 USA. [Schmidt, Folke; Rickman, David S.; Scherr, Douglas; Rubin, Mark A.] Weill Cornell Med Coll, Dept Lab Med, New York, NY 10065 USA. [Laxman, Bharathi; Siddiqui, Javed; Tomlins, Scott A.; Wei, John T.; Chinnaiyan, Arul M.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Laxman, Bharathi; Siddiqui, Javed; Tomlins, Scott A.; Wei, John T.; Chinnaiyan, Arul M.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Sanda, MG (reprint author), Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02215 USA. EM msanda@bidmc.harvard.edu RI Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012; OI Rubin, Mark/0000-0002-8321-9950 FU NCI-EDRN CEVC [U01 CA113913] FX Funding was provided by NCI-EDRN CEVC U01 CA113913. SAT, AC, and MAR are listed as inventors in a patent related to diagnostic use of TMPRSS2:ERG. NR 28 TC 62 Z9 64 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL PY 2013 VL 31 IS 5 BP 566 EP 571 DI 10.1016/j.urolonc.2011.04.001 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 180LV UT WOS:000321597600008 PM 21600800 ER PT J AU Davis, RK Doane, MG Knop, E Knop, N Dubielzig, RR Colitz, CMH Argueso, P Sullivan, DA AF Davis, Robin Kelleher Doane, Marshall G. Knop, Erich Knop, Nadja Dubielzig, Richard R. Colitz, Carmen M. H. Argueeso, Pablo Sullivan, David A. TI Characterization of ocular gland morphology and tear composition of pinnipeds SO VETERINARY OPHTHALMOLOGY LA English DT Article DE meibomian glands; ocular surface; pinnipeds; tear film ID DOLPHIN TURSIOPS-TRUNCATUS; INTERNATIONAL WORKSHOP; DYSFUNCTION REPORT; MEIBOMIAN GLAND; FILM; SURFACE; INTERFEROMETRY; SUBCOMMITTEE; SECRETIONS; FEATURES AB Objective The importance of tear film integrity to ocular health in terrestrial mammals is well established, however, in marine mammals, the role of the tear film in protection of the ocular surface is not known. In an effort to better understand the function of tears in maintaining health of the marine mammal eye surface, we examined ocular glands of the California sea lion and began to characterize the biochemical nature of the tear film of pinnipeds. Procedures Glands dissected from California sea lion eyelids and adnexa were examined for gross morphology, sectioned for microscopic analysis, and stained with hematoxylin and eosin. The tear film was examined using interferometry. Tears were collected from humans and pinnipeds for the analysis of protein and carbohydrate content. Results The sea lion has sebaceous glands in the lid, but these glands are different in size and orientation compared with typical meibomian glands of terrestrial mammals. Two other accessory ocular glands located dorsotemporally and medially appeared to be identical in morphology, with tubulo-acinar morphology. An outer lipid layer on the ocular surface of the sea lion was not detected using interferometry, consistent with the absence of typical meibomian glands. Similar to human tears, the tears of pinnipeds contain several proteins but the ratio of carbohydrate to protein was greater than that in human tears. Conclusions Our findings indicate that the ocular gland architecture and biochemical nature of the tear film of pinnipeds have evolved to adapt to the challenges of an aquatic environment. C1 [Davis, Robin Kelleher; Doane, Marshall G.; Argueeso, Pablo; Sullivan, David A.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Davis, Robin Kelleher; Doane, Marshall G.; Argueeso, Pablo; Sullivan, David A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Knop, Erich; Knop, Nadja] Charite Univ Med Berlin, Dept Cell & Neurobiol, OSCB, Berlin, Germany. [Dubielzig, Richard R.] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. [Colitz, Carmen M. H.] Aquat Anim Eye Care LLC, Jupiter, FL USA. [Colitz, Carmen M. H.] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. [Colitz, Carmen M. H.] Univ Florida, Coll Vet Med, Courtesy Fac Appointment, Gainesville, FL USA. RP Davis, RK (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM robin.kdavis@schepens.harvard.edu FU NIH [EY05612, EY014847]; Arey's Pond Boat Yard (South Orleans, MA); German Federal Research Foundation [DFG KN317/11] FX Support: NIH grants EY05612 (DAS) & EY014847 (PA); Arey's Pond Boat Yard (South Orleans, MA); and DFG KN317/11 (German Federal Research Foundation), and the National Oceanic and Atmospheric Administration (NOAA) for permission to obtain marine mammal tissues for the purposes of research. The authors thank the Marine Mammal Center (Sausalito, CA) for contributions of tissues, the New England Aquarium (Boston, MA) and Niagara Aquarium (Niagara, NY) for provision of pinniped tear samples, and Wendy Kam for technical support. NR 33 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1463-5216 J9 VET OPHTHALMOL JI Vet. Ophthalmol. PD JUL PY 2013 VL 16 IS 4 BP 269 EP 275 DI 10.1111/j.1463-5224.2012.01073.x PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 176TH UT WOS:000321327300004 ER PT J AU Pennington, DL Durazzo, TC Schmidt, TP Mon, A Abe, C Meyerhoff, DJ AF Pennington, David L. Durazzo, Timothy C. Schmidt, Thomas P. Mon, Anderson Abe, Christoph Meyerhoff, Dieter J. TI The Effects of Chronic Cigarette Smoking on Cognitive Recovery During Early Abstinence from Alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Cigarette Smoking; Cognition; Treatment; Former Smoking ID NEUROCOGNITIVE FUNCTION; DEPENDENT INDIVIDUALS; NICOTINE DEPENDENCE; MAJOR DEPRESSION; DRINKING HISTORY; USE DISORDERS; CONSUMPTION; PERFORMANCE; DEFICITS; CONSEQUENCES AB Background Alcohol use disorders are related to neurocognitive abnormalities during early abstinence in those seeking treatment for alcohol dependence (ALC). Considerable evidence indicates that chronic cigarette smoking is associated with multiple neurocognitive deficiencies. However, very little is known about the effects of chronic smoking on neurocognitive recovery during early abstinence from alcohol. We evaluated whether cigarette smoking interferes with cognitive improvement during early abstinence from alcohol, a period thought important for maintaining long-term sobriety. Methods Neurocognitive functions previously shown to be adversely affected by both alcohol use disorders and chronic cigarette smoking were evaluated. We assessed 35 smoking ALC (sALC) and 34 nonsmoking ALC (nsALC) at approximately 1 and 5weeks of monitored abstinence. Results Although neither group was clinically impaired, both cross-sectional and longitudinal deficiencies were observed in sALC versus nsALC in processing speed, working memory, and auditory-verbal learning and memory. Lifetime alcohol consumption, medical, and psychiatric comorbidities did not predict neurocognitive performance or improvement across assessments. Within sALC, greater drinking and smoking severities were synergistically (more than additively) related to less improvement on visuospatial learning and memory. Former smoking status in the nsALC-mediated group differences in auditory-verbal delayed recall. Conclusions Chronic cigarette smoking appears to negatively impact neurocognition during early abstinence from alcohol. Although the cognitive deficiencies observed in this cohort were not in a clinical range of impairment, they should be considered to enhance treatment efficacy. Our findings lend support to integrating smoking cessation as well as the individual assessment of cognition into early ALC treatment. Additionally, there is a need to elucidate the effects of current and former smoking status in future reports of neurocognition. C1 [Pennington, David L.; Durazzo, Timothy C.; Schmidt, Thomas P.; Mon, Anderson; Abe, Christoph; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Pennington, David L.; Durazzo, Timothy C.; Schmidt, Thomas P.; Mon, Anderson; Abe, Christoph; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Pennington, DL (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM david.pennington@ucsf.edu OI Abe, Christoph/0000-0002-1680-8480 FU National Institutes of Health [AA10788, DA24136] FX This work was supported by grants from the National Institutes of Health (AA10788 to DJM; DA24136 to TCD) administered by the Northern California Institute for Research and Education, and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. We thank Mary Rebecca Young, Kathleen Altieri, Ricky Chen, and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital (which routinely offers smoking cessation with substance abuse treatment), and Dr. David Pating, Karen Moise, and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 54 TC 11 Z9 12 U1 0 U2 9 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 JUL PY 2013 VL 37 IS 7 BP 1220 EP 1227 DI 10.1111/acer.12089 PG 8 WC Substance Abuse SC Substance Abuse GA 175TR UT WOS:000321256800019 PM 23432133 ER PT J AU Rienstra, M Lyass, A Murabito, JM Magnani, JW Lubitz, SA Massaro, JM Ellinor, PT Benjamin, EJ AF Rienstra, Michiel Lyass, Asya Murabito, Joanne M. Magnani, Jared W. Lubitz, Steven A. Massaro, Joseph M. Ellinor, Patrick T. Benjamin, Emelia J. TI Reciprocal relations between physical disability, subjective health, and atrial fibrillation: The Framingham Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID FUNCTIONAL STATUS; OLDER-ADULTS; COMMUNITY; RHYTHM; DISEASE; EXERCISE AB Background Atrial fibrillation (AF)-related symptoms and physical performance are relied upon to guide therapeutic management of patients with AF. We sought to understand whether AF predisposes to or is a result of physical disability and poor subjective health in the community. Methods We studied relations between physical disability (Rosow-Breslau Functional Health Scale), subjective health (self-report) and incident AF, and the converse, in the Framingham Heart Study. Results In 3,609 participants (age 73 +/- 8 years, 59% women), a subset of 861 participants (24%) had prevalent physical disability at baseline. During 5.8 +/- 1.8 years of follow-up, 555 participants (10-year age-and sex-adjusted incidence rate 13%) developed incident AF. Prevalent physical disability was related to incident AF (multivariable-adjusted hazard ratio 1.25, 95% CI 1.02-1.54, P =.03). In 3,525 participants, prevalent poor subjective health (n = 333) also was related to incident AF (n = 552, multivariable-adjusted hazard ratio 1.31, 95% CI 1.00-1.70, P =.048). Conversely, in 2,080 participants (age 69 +/- 6 years, 55% women), interim AF (n = 106) was associated with newly reported physical disability (n = 573) at a follow-up examination (multivariable-adjusted odds ratio 1.58, 95% CI 1.08-2.31, P =.01). In 1,954 participants, interim AF (n = 96) likewise was related to newly reported poor subjective health (n = 224, multivariable-adjusted odds ratio 1.83, 95% CI 1.10-3.02, P = .02). Conclusions Physical disability and poor subjective health were related to incident AF in a community-based cohort. Conversely, interim AF was related to newly reported physical disability and poor subjective health. Because AF guidelines incorporate symptoms, it is essential to clarify the temporality and mechanisms linking physical disability, subjective health, and AF. C1 [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Rienstra, Michiel; Lyass, Asya; Murabito, Joanne M.; Magnani, Jared W.; Massaro, Joseph M.; Benjamin, Emelia J.] NHLBIs & Boston Univ Framingham Heart Study, Framingham, MA USA. [Lyass, Asya] Boston Univ, Dept Math, Boston, MA 02215 USA. [Murabito, Joanne M.] Boston Univ, Gen Internal Med Sect, Boston, MA 02215 USA. [Magnani, Jared W.] Boston Univ, Sect Cardiovasc Med, Boston, MA 02215 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Massaro, Joseph M.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU NIH [1R01HL092577, 1RC1HL101056, 1R01HL102214, R01AG028321, 6R01-NS 17950, 5R21DA027021, 5RO1HL104156, 1K24HL105780, R01-AG29451]; Boston University Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation Initiative; Netherlands Organization for Scientific Research [825.09.020]; American Heart Association Award [09FTF2190028]; [N01-HC 25195] FX This work was supported by grants from the NIH to Drs Benjamin and Ellinor (1R01HL092577), Dr Benjamin (1RC1HL101056, 1R01HL102214, and R01AG028321 and support via 6R01-NS 17950), Dr Ellinor (5R21DA027021, 5RO1HL104156, and 1K24HL105780), and Dr Murabito (R01-AG29451). This work was partially supported by the Boston University Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation Initiative. The Framingham Heart Study is supported by N01-HC 25195. Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Rubicon Grant 825.09.020). Dr Magnani is supported by American Heart Association Award 09FTF2190028. NR 26 TC 7 Z9 7 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 JUL PY 2013 VL 166 IS 1 BP 171 EP + DI 10.1016/j.ahj.2013.02.025 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 173AW UT WOS:000321051400024 PM 23816037 ER PT J AU Ahmad, FS Metlay, JP Barg, FK Henderson, RR Werner, RM AF Ahmad, Faraz S. Metlay, Joshua P. Barg, Frances K. Henderson, Rebecca R. Werner, Rachel M. TI Identifying Hospital Organizational Strategies to Reduce Readmissions SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE readmissions; quality; qualitative methods; care transitions ID MYOCARDIAL-INFARCTION; 30-DAY READMISSIONS; QUALITY; PROGRAM AB With looming financial penalties for institutions with high readmission rates, hospital administrators are under pressure to implement strategies to reduce readmissions despite limited evidence of effective strategies. The objectives of this study were to understand the process of developing readmission reduction strategies and to identify and categorize the range of strategies being implemented. The authors designed a qualitative study using semistructured interviews with 12 hospital administrators at 6 different hospitals. The following 6 categories of strategies were identified: (a) tracking readmissions, (b) using prediction tools, (c) implementing disease-specific or generic readmission reduction programs, (d) adopting electronic health record-based strategies to improve transitions, (e) recruiting frontline staff for program leadership, and (f) coordinating with primary care providers. The results highlight the myriad approaches to readmission reduction and the complexity of developing effective strategies. C1 [Ahmad, Faraz S.; Metlay, Joshua P.; Barg, Frances K.; Henderson, Rebecca R.; Werner, Rachel M.] Univ Penn, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Ahmad, FS (reprint author), Hosp Univ Penn, 3400 Spruce St,100 Centrex, Philadelphia, PA 19104 USA. EM Faraz.Ahmad@uphs.upenn.edu FU Center for Healthcare Improvement & Patient Safety in the Department of Medicine at the Perelman School of Medicine of the University of Pennsylvania FX The authors received the following financial support for the research, authorship, and/or publication of this article: This study was funded by Center for Healthcare Improvement & Patient Safety in the Department of Medicine at the Perelman School of Medicine of the University of Pennsylvania. NR 20 TC 6 Z9 6 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JUL PY 2013 VL 28 IS 4 BP 278 EP 285 DI 10.1177/1062860612464999 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 176XM UT WOS:000321340100001 PM 23118202 ER PT J AU Borzecki, AM Cevasco, M Chen, Q Shin, M Itani, KM Rosen, AK AF Borzecki, Ann M. Cevasco, Marisa Chen, Qi Shin, Marlena Itani, Kamal M. Rosen, Amy K. TI Improving Identification of Postoperative Respiratory Failure Missed by the Patient Safety Indicator Algorithm SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE postoperative respiratory failure; patient safety; adverse events; quality of care; quality indicators AB The Patient Safety Indicator postoperative respiratory failure (PRF) flags cases using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for acute respiratory failure or mechanical ventilation/intubation. The authors examined how frequently PRF missed events and ways to improve event identification. A total of 125 high-risk unflagged cases were selected based on predicted probability and presence of clinically relevant codes. False-negative (FN) proportion and associated reasons were determined through chart review, and likelihood ratios (LRs) of associated codes were calculated. In all, 27% of elective cases were FNs; 55% of FNs lacked ventilation/intubation codes. Respiratory arrest, 799.1, had the highest LR (5.4) but occurred in only 8% of FNs. All other individual diagnostic or procedure codes had relatively low LRs (3.1), despite occurring in up to 36% of FNs. Among high-risk cases, the PRF algorithm often missed events. Improved ventilation/intubation coding will have more of an impact on case identification than adding ICD-9-CM codes to the algorithm. C1 [Borzecki, Ann M.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Borzecki, Ann M.; Itani, Kamal M.; Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Cevasco, Marisa; Chen, Qi; Shin, Marlena; Itani, Kamal M.; Rosen, Amy K.] VA Boston Healthcare Syst, Boston, MA USA. [Cevasco, Marisa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Itani, Kamal M.] Harvard Univ, Sch Med, Boston, MA USA. RP Borzecki, AM (reprint author), Bedford VA Hosp 152, CHQOER, 200 Springs Rd, Bedford, MA 01730 USA. EM amb@bu.edu FU Department of Veterans Affairs Health Services Research and Development Service [SDR 07-002] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Department of Veterans Affairs Health Services Research and Development Service Grant Number SDR 07-002. NR 21 TC 2 Z9 2 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JUL PY 2013 VL 28 IS 4 BP 315 EP 323 DI 10.1177/1062860612468482 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 176XM UT WOS:000321340100006 PM 23221120 ER PT J AU Simon, HB AF Simon, Harvey B. TI Naming Right: Gnostic Nomenclature vs Useful Names SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ATHEROSCLEROSIS; CANCER C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. [Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, HB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM hsimon@partners.org NR 17 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 2013 VL 126 IS 7 BP 654 EP 656 DI 10.1016/j.amjmed.2013.02.010 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 167RE UT WOS:000320649800036 PM 23688664 ER PT J AU Kamran, SC Pendergraft, WF Harmon, DC Rubin, MF AF Kamran, Sophia C. Pendergraft, William F. Harmon, David C. Rubin, Mario F. TI Ifosfamide-induced Fanconi Syndrome and Desmopressin-responsive Nephrogenic Diabetes Insipidus SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kamran, Sophia C.] Harvard Univ, Sch Med, Boston, MA USA. [Pendergraft, William F.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Harmon, David C.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Rubin, Mario F.] Univ Arizona, Div Nephrol, Dept Med, Med Ctr, Tucson, AZ 85724 USA. RP Rubin, MF (reprint author), Univ Arizona, Div Nephrol, Dept Med, Med Ctr, 1501 N Campbell Ave,Room 6325,POB 245022, Tucson, AZ 85724 USA. EM mrubin@deptofmed.arizona.edu OI Kamran, Sophia/0000-0001-9283-6515 NR 4 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 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2013 VL 126 IS 7 BP E7 EP E8 DI 10.1016/j.amjmed.2013.02.005 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 167RE UT WOS:000320649800003 PM 23684064 ER PT J AU Lange, N Litonjua, AA Gibbons, FK Giovannucci, E Christopher, KB AF Lange, Nancy Litonjua, Augusto A. Gibbons, Fiona K. Giovannucci, Edward Christopher, Kenneth B. TI Pre-hospital Vitamin D Concentration, Mortality, and Bloodstream Infection in a Hospitalized Patient Population SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Bloodstream infection; Mortality; Vitamin D ID SERUM 25-HYDROXYVITAMIN D; NUTRITION EXAMINATION SURVEY; PLACEBO-CONTROLLED TRIAL; 3RD NATIONAL-HEALTH; D SUPPLEMENTATION; CRITICAL-CARE; D DEFICIENCY; RISK; ASSOCIATION; MICE AB OBJECTIVE: The study objective was to examine the association between pre-hospital serum vitamin D concentration and mortality after hospitalization. METHODS: We performed a retrospective cohort study in 2 tertiary hospitals in Boston, Mass, on 23,603 patients aged >= 18 years in whom 25(OH) D was measured before hospitalization between 1993 and 2010. The main outcome measures were all-cause mortality by day 30 post-hospital admission, in-hospital mortality, and community-acquired bloodstream infection. RESULTS: Compared with patients with pre-hospital 25(OH) D >= 30 ng/mL, patients with pre-hospital 25(OH) D <= 15 ng/mL or 15 to 30 ng/mL have higher odds of mortality 30 days after hospital admission. After adjustment for age, gender, race, Deyo-Charlson index, season, type (surgical vs medical), creatinine, blood urea nitrogen, hematocrit, and time between 25(OH) D draw and hospital admission, the adjusted odds ratio (OR) of 30-day mortality in patients with 25(OH) D <= 15 ng/mL is 1.45 (95% confidence interval [CI], 1.21-1.74; P<.0001) and the adjusted OR of 30-day mortality in patients with 25(OH) D 15 to 30 ng/mL is 1.30 (95% CI, 1.10-1.54; P = .003) both compared with patients with pre-hospital 25(OH) D >= 30 ng/mL. In a subgroup analysis of patients who had blood cultures drawn (n = 5628), pre-hospital serum 25(OH) D <= 15 ng/mL was associated with increased odds of community-acquired bloodstream infection (adjusted OR, 1.29; 95% CI, 1.06-1.57; P = .01) relative to patients with 25(OH) D >= 30 ng/mL. CONCLUSIONS: Analysis of 23,603 hospitalized patients identified both 25(OH) D <= 15 ng/mL and 25(OH) D 15 to 30 ng/mL before hospital admission as associated with the odds of all-cause patient mortality at 30 days after hospitalization. In addition, pre-hospital serum 25(OH) D <= 15 ng/mL is significantly associated with the odds of community-acquired bloodstream infection. (C) 2013 Elsevier Inc. All rights reserved. C1 [Lange, Nancy] Brigham & Womens Hosp, Div Pulm, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Boston, MA 02114 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. [Christopher, Kenneth B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org OI Litonjua, Augusto/0000-0003-0422-5875 NR 50 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2013 VL 126 IS 7 AR 640.e19 DI 10.1016/j.amjmed.2012.12.014 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 167RE UT WOS:000320649800031 PM 23787198 ER PT J AU Hofmann, SG Smits, JAJ Rosenfield, D Simon, N Otto, MW Meuret, AE Marques, L Fang, A Tart, C Pollack, MH AF Hofmann, Stefan G. Smits, Jasper A. J. Rosenfield, David Simon, Naomi Otto, Michael W. Meuret, Alicia E. Marques, Luana Fang, Angela Tart, Candyce Pollack, Mark H. TI D-Cycloserine as an Augmentation Strategy With Cognitive-Behavioral Therapy for Social Anxiety Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; EXPOSURE THERAPY; EXTINCTION; PHOBIA; PHENELZINE; PSYCHOTHERAPY AB Objective: The authors examined whether D-cycloserine, a partial agonist at the glutamatergic N-methyl-D-aspartate receptor, augments and accelerates a full course of comprehensive cognitive-behavioral therapy (CBT) in adults with generalized social anxiety disorder. Method: This was a multisite randomized placebo-controlled efficacy study with 169 medication-free adults with generalized social anxiety disorder, of whom 144 completed the 12-week treatment and 131 completed the three follow-up assessments. Patients were randomly assigned to receive 50 mg of D-cycloserine or placebo 1 hour before each of five exposure sessions that were part of a 12-session cognitive-behavioral group treatment. Response and remission status was determined at baseline, throughout treatment, at end of treatment, and at 1-, 3-, and 6-month follow-up assessments by assessors who were blind to treatment condition. Results: D-Cycloserine-augmented and placebo-augmented CBT were associated with similar completion rates (87% and 82%), response rates (79.3% and 73.3%), and remission rates (34.5% and 24.4%) at the posttreatment assessment; response and remission rates were largely maintained at the follow-up assessments. Although D-cycloserine was associated with a 24%-33% faster rate of improvement in symptom severity and remission rates relative to placebo during the treatment phase, the groups did not differ in response and remission rates. Conclusions: D-Cycloserine did not augment a full course of comprehensive CBT for social anxiety disorder. C1 [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014; Smits, Jasper/A-4350-2008; OI Hofmann, Stefan/0000-0002-3548-9681; Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 FU American Foundation for Suicide Prevention; Forest Laboratories; NIMH [R01MH078308, R01MH075889]; Department of Defense; Bristol-Myers Squibb; Euthymics; Eli Lilly; GlaxoSmithKline; Medavante; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; Otsuka; Targia Pharmaceuticals FX Dr. Hofmann has received royalties from multiple publishers, including Routledge, the publisher of the CBT manual used in this study. Dr. Smits has received royalties from multiple publishers. Dr. Simon has received research support from the American Foundation for Suicide Prevention, Forest Laboratories, NIMH, and the Department of Defense and has participated in CME activity in the Massachusetts General Hospital Psychiatry Academy; her spouse has equity in Elan, Dandreon, G Zero, and Gatekeeper. Dr. Otto has served as a consultant for Micro Transponder and has received royalties from multiple publishers, including Routledge, the publisher of the CBT manual used in this study. Dr. Meuret has served as a consultant for Palo Alto Health Sciences. Dr. Pollack has served as an adviser or consultant for or received research support from Bristol-Myers Squibb, Euthymics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Medavante, National Center for Complementary and Alternative Medicine, National Institute on Drug Abuse, NIMH, Otsuka, and Targia Pharmaceuticals; he has equity in Medavante, Mensante Corporation, Mindsite, and Targia Pharmaceuticals, and he receives royalties for the SIGH-A and SAFER interviews.; Supported by NIMH grant R01MH078308 to Dr. Hofmann and grant R01MH075889 to Dr. Pollack. NR 40 TC 48 Z9 48 U1 1 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2013 VL 170 IS 7 BP 751 EP 758 DI 10.1176/appi.ajp.2013.12070974 PG 8 WC Psychiatry SC Psychiatry GA 172RX UT WOS:000321023700011 PM 23599046 ER PT J AU McBride, SM Raut, CP Lapidus, M Devlin, PM Marcus, KJ Bertagnolli, M George, S Baldini, EH AF McBride, Sean M. Raut, Chandrajit P. Lapidus, Michelle Devlin, Phillip M. Marcus, Karen J. Bertagnolli, Monica George, Suzanne Baldini, Elizabeth H. TI Locoregional Recurrence After Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Adverse Impact of Multifocal Disease and Potential Implications of Dose Escalation SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMA; RESECTION PREDICT PATTERN; HISTOLOGIC SUBTYPE; SURVIVAL; MARGIN; BRACHYTHERAPY; RADIOTHERAPY; LIPOSARCOMA; OUTCOMES; TRIAL AB Locoregional recurrence (LRR) rates following preoperative radiation therapy (RT) and radical resection for retroperitoneal sarcoma (RPS) are high. Targeted radiation dose escalation has been proposed as a means to decrease LRR, but is applicable only if LRRs are confined to within the RT field. We analyzed predictors for LRR and examined LRR locations to determine the potential benefit of dose escalation. For 33 patients treated with preoperative RT and radical resection, we determined high-risk tumor volumes appropriate for boost and identified the number of recurrences within this volume. Clinical and pathologic variables predictive of overall survival (OS), freedom from progression (FFP), LRR, and distant recurrence (DR) were evaluated. Median follow-up was 32.9 months. At 1 and 3 years, OS was 87 and 64 %, FFP rates were 71 and 45 %, cumulative incidences of LRR were 19 and 37 %, and of DR were 13 and 21 %. On multivariate analysis, multifocal disease was a significant predictor of increased incidence of LRR. At first relapse, 6 patients had isolated LR, 2 isolated RR, 6 isolated DR, 1 synchronous LR and RR, and 1 synchronous LR, RR, and DR. Ultimately, 4 patients (25 % of those who recurred) had isolated in-field recurrences within the hypothetical high-risk dose-painting boost volumes and that thus might have been prevented with dose-escalation. Following preoperative RT and resection, LRR rates are high and associated with multifocal disease. Preoperative dose escalation to high-risk tumor volumes may perhaps benefit only a limited subset of patients, and therefore strategies are needed to select appropriate patients for consideration of this approach. C1 [McBride, Sean M.] Harvard Radiat Oncol Program, Boston, MA USA. [Raut, Chandrajit P.; Lapidus, Michelle; Bertagnolli, Monica] Brigham & Womens Hosp, Dept Surg Oncol, Boston, MA 02115 USA. [Raut, Chandrajit P.; Devlin, Phillip M.; Marcus, Karen J.; Bertagnolli, Monica; George, Suzanne; Baldini, Elizabeth H.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Devlin, Phillip M.; Marcus, Karen J.; Baldini, Elizabeth H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Devlin, Phillip M.; Marcus, Karen J.; Baldini, Elizabeth H.] Childrens Hosp, Boston, MA 02115 USA. [George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP McBride, SM (reprint author), Harvard Radiat Oncol Program, Boston, MA USA. EM smmcbride@partners.org NR 32 TC 26 Z9 27 U1 0 U2 3 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 JUL PY 2013 VL 20 IS 7 BP 2140 EP 2147 DI 10.1245/s10434-013-2868-y PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 159JC UT WOS:000320040700009 PM 23392853 ER PT J AU Khandekar, MJ Raut, CP Hornick, JL Wang, Q Alexander, BM Baldini, EH AF Khandekar, Melin J. Raut, Chandrajit P. Hornick, Jason L. Wang, Qian Alexander, Brian M. Baldini, Elizabeth H. TI Paratesticular Liposarcoma: Unusual Patterns of Recurrence and Importance of Margins SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SOFT-TISSUE SARCOMA; RESECTION PREDICT PATTERN; SPERMATIC CORD SARCOMA; RADIATION-THERAPY; RETROPERITONEAL LIPOSARCOMA; HISTOLOGIC SUBTYPE; PROGNOSTIC-FACTORS; SURGICAL MARGINS; RE-EXCISION; MANAGEMENT AB Paratesticular liposarcoma (LPS) is a rare entity for which optimal treatment has not been defined. We sought to determine recurrence patterns and prognostic factors. A total of 25 patients with localized paratesticular LPS between 1987 and 2009 were reviewed. Actuarial local-recurrence-free survival (LRFS), disease-free-survival (DFS), and overall survival (OS) were determined using the Kaplan-Meier method. LPS histology was well differentiated for 10 patients (40 %), de-differentiated for 14 (56 %), and pleomorphic for 1 (4 %). Final margins were positive in 8 patients (32 %). Radiation therapy (RT) was given to 10 patients; fields included inguinal canal +/- A scrotum and low pelvis. LRFS rates at 3 and 5 years were 76 and 67 %. The 3-year LRFS rates were lower in patients with positive margins compared with those with negative margins (29 vs 100 %, p = .0005) and in patients with recurrent versus primary disease (38 vs 83 %, p = .04). Among patients who received surgery and RT, margins remained a significant predictor of local recurrence (p = .009). Interestingly, recurrences in 4 patients tracked along gonadal vessels, and only 1 patient had a distant recurrence. OS at 5 years was 100 %. For patients with localized paratesticular LPS, positive margins and presentation with recurrent disease are adverse prognostic factors for LRFS. LR for patients with positive margins is still high despite RT; thus aggressive surgery to attain negative margins should be attempted in all cases. The finding of regional recurrences along gonadal vessels should be validated, and imaging studies should be tailored to reflect potential patterns of disease at presentation and subsequent recurrence. C1 [Khandekar, Melin J.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Div Surg Oncol, Sch Med, Boston, MA 02115 USA. [Raut, Chandrajit P.; Hornick, Jason L.; Alexander, Brian M.; Baldini, Elizabeth H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Raut, Chandrajit P.; Hornick, Jason L.; Baldini, Elizabeth H.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wang, Qian] Beijing Novartis Pharma Co Ltd, Beijing, Peoples R China. [Alexander, Brian M.; Baldini, Elizabeth H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Baldini, EH (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. EM ebaldini@partners.org NR 35 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 2013 VL 20 IS 7 BP 2148 EP 2155 DI 10.1245/s10434-013-2963-0 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 159JC UT WOS:000320040700010 PM 23591942 ER PT J AU Gold, JS Al Natour, RH Saund, MS Yoon, C Sharma, AM Huang, Q Boosalis, VA Whang, EE AF Gold, Jason S. Al Natour, Riad H. Saund, Mandeep S. Yoon, Charles Sharma, Ashish M. Huang, Qin Boosalis, Valia A. Whang, Edward E. TI Population-Based Outcome of Stage IA-IIA Resected Gastric Adenocarcinoma: Who Should Get Adjuvant Treatment? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PERIOPERATIVE CHEMOTHERAPY; CANCER STATISTICS; SURGERY; SURVIVAL; CLASSIFICATION; GASTRECTOMY; CARCINOMA; STOMACH; DISEASE AB The benefit of adjuvant treatment in gastric adenocarcinoma was demonstrated by randomized, controlled trials of patients with locally advanced tumors. Thus, its role for stage IIB-IIIC disease is widely accepted. We aimed to identify patients with stage IA-IIA gastric adenocarcinoma who have a poor prognosis and thus may benefit from adjuvant treatment. Patients with gastric adenocarcinoma who underwent surgical resection with pathological evaluation of a parts per thousand yen15 lymph nodes and had available disease-specific survival (DSS) data were identified from the Surveillance Epidemiology and End Results Registry. Survival differences were evaluated with the log-rank test and Cox multivariate analysis. Stage and TN grouping strongly predicted DSS (P < 0.001, P < 0.001). Stage IA tumors had an excellent outcome: 91 +/- A 1.2 % 5-year DSS. The TN groupings of stages IB and IIA had the next best outcomes with 5-year DSS from 66 +/- A 4.6 % to 81 +/- A 2.3 %. Older age (P < 0.001), higher grade (P = 0.004), larger tumor size (P < 0.001), and proximal tumor location (P < 0.001) were independent predictors of worse DSS in stage IB-IIA tumors. We devised a risk stratification scheme for stage IB-IIA tumors where 1 point was assigned for age > 60 years, tumor size > 5 cm, proximal tumor location, and grade other than well-differentiated. Five-year DSS was 100 % for patients with 0 points; 86 +/- A 4.3 %, 1 point; 76 +/- A 3 %, 2 points; 72 +/- A 2.8 %, 3 points; and 48 +/- A 4.9 %, 4 points (P < 0.001). Patients with stage IB-IIA gastric adenocarcinoma and a parts per thousand yen2 adverse features (age > 60 years, tumor size > 5 cm, proximal location, and high-grade) have 5-year DSS a parts per thousand currency sign76 %. Adjuvant therapy may be warranted for these patients. C1 [Gold, Jason S.; Al Natour, Riad H.; Whang, Edward E.] VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA. [Gold, Jason S.; Al Natour, Riad H.; Saund, Mandeep S.; Yoon, Charles; Whang, Edward E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gold, Jason S.; Al Natour, Riad H.; Saund, Mandeep S.; Yoon, Charles; Huang, Qin; Whang, Edward E.] Harvard Univ, Sch Med, Boston, MA USA. [Sharma, Ashish M.; Boosalis, Valia A.] VA Boston Healthcare Syst, Med Serv, West Roxbury, MA USA. [Sharma, Ashish M.; Boosalis, Valia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Huang, Qin] VA Boston Healthcare Syst, Pathol Serv, West Roxbury, MA USA. RP Gold, JS (reprint author), VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA. EM jgold4@partners.org RI Gold, Jason/O-5112-2014 OI Gold, Jason/0000-0002-2925-4755 FU Department of Veterans Affairs Office of Research and Development through a Career Development [2] FX This work is supported by the Department of Veterans Affairs Office of Research and Development through a Career Development Award-2 (JSG). NR 25 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 2013 VL 20 IS 7 BP 2304 EP 2310 DI 10.1245/s10434-012-2852-y PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 159JC UT WOS:000320040700032 PM 23344580 ER PT J AU Townsend, KL An, D Lynes, MD Huang, TL Zhang, HB Goodyear, LJ Tseng, YH AF Townsend, Kristy L. An, Ding Lynes, Matthew D. Huang, Tian Lian Zhang, Hongbin Goodyear, Laurie J. Tseng, Yu-Hua TI Increased Mitochondrial Activity in BMP7-Treated Brown Adipocytes, Due to Increased CPT1- and CD36-Mediated Fatty Acid Uptake SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID BONE MORPHOGENETIC PROTEIN-7; WHITE ADIPOSE-TISSUE; METABOLIC SYNDROME; ADULT HUMANS; ADAPTIVE THERMOGENESIS; OXIDATIVE-METABOLISM; SKELETAL-MUSCLE; GENE-EXPRESSION; BETA-OXIDATION; IN-VIVO AB Aims: Brown adipose tissue dissipates chemical energy in the form of heat and regulates triglyceride and glucose metabolism in the body. Factors that regulate fatty acid uptake and oxidation in brown adipocytes have not yet been fully elucidated. Bone morphogenetic protein 7 (BMP7) is a growth factor capable of inducing brown fat mitochondrial biogenesis during differentiation from adipocyte progenitors. Administration of BMP7 to mice also results in increased energy expenditure. To determine if BMP7 is able to affect the mitochondrial activity of mature brown adipocytes, independent of the differentiation process, we delivered BMP7 to mature brown adipocytes and measured mitochondrial activity. Results: We found that BMP7 increased mitochondrial activity, including fatty acid oxidation and citrate synthase activity, without increasing the mitochondrial number. This was accompanied by an increase in fatty acid uptake and increased protein expression of CPT1 and CD36, which import fatty acids into the mitochondria and the cell, respectively. Importantly, inhibition of either CPT1 or CD36 resulted in a blunting of the mitochondrial activity of BMP7-treated cells. Innovation: These findings uncover a novel pathway regulating mitochondrial activities in mature brown adipocytes by BMP7-mediated fatty acid uptake and oxidation. Conclusion: In conclusion, BMP7 increases mitochondrial activity in mature brown adipocytes via increased fatty acid uptake and oxidation, a process that requires the fatty acid transporters CPT1 and CD36. C1 [Townsend, Kristy L.; An, Ding; Lynes, Matthew D.; Huang, Tian Lian; Zhang, Hongbin; Goodyear, Laurie J.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Tseng, YH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM yu-hua.tseng@joslin.harvard.edu FU NIH [R01 DK077097, F32 DK091996]; Joslin Diabetes Center's Diabetes Research Center from the NIDDK [P30 DK036836]; Eli Lilly Research Foundation; Harvard Stem Cell Institute FX The authors wish to thank the following people for technical advice: Cecile Vernochet, Andre Kleinridders, Chris Cahill, Kristina Kriauciunas, Carly Cederquist, Stephane Gesta and C. Ronald Kahn (Joslin Diabetes Center), and Zhiyong Cheng (Children's Hospital). We thank Lindsay McDougall (Joslin Diabetes Center) for technical assistance, Eric Widmaier (Boston University) and Paul Yu (Brighm and Women's Hospital) for reagents, and Tim Schulz (Joslin Diabetes Center) for critical reading of the manuscript. We acknowledge Stryker Regenerative Medicine (Hopkinton, MA) for the generous gift of recombinant BMP7 for the in vivo experiments. This work was supported in part by the NIH grants R01 DK077097 (Y.-H.T.), Joslin Diabetes Center's Diabetes Research Center (P30 DK036836 from the NIDDK), and a research grant from the Eli Lilly Research Foundation and by funding from Harvard Stem Cell Institute (to Y.-H.T.). KLT was supported by NIH F32 DK091996. NR 63 TC 22 Z9 23 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUL PY 2013 VL 19 IS 3 BP 243 EP 257 DI 10.1089/ars.2012.4536 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 172XO UT WOS:000321040300004 PM 22938691 ER PT J AU Ellett, JD Rosoff, JS Prasad, SM AF Ellett, Justin D. Rosoff, James S. Prasad, Sandip M. TI Long-term differences in urinary, bowel and sexual function among men treated with surgery versus radiation for prostate cancer SO ASIAN JOURNAL OF ANDROLOGY LA English DT Editorial Material ID ACTIVE SURVEILLANCE; OUTCOMES C1 [Ellett, Justin D.; Rosoff, James S.; Prasad, Sandip M.] Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. [Prasad, Sandip M.] Ralph H Johnson VA Med Ctr, Urol Sect, Charleston, SC 29401 USA. RP Prasad, SM (reprint author), Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. EM prasads@musc.edu NR 10 TC 1 Z9 1 U1 1 U2 6 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD JUL PY 2013 VL 15 IS 4 BP 443 EP 444 DI 10.1038/aja.2013.39 PG 2 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 174XE UT WOS:000321190000003 PM 23665759 ER PT J AU Lim, S Hong, J Liu, CT Hivert, MF White, CC Murabito, JM O'Donnell, CJ Dupuis, J Florez, JC Meigs, JB AF Lim, Soo Hong, Jaeyoung Liu, Ching-Ti Hivert, Marie-France White, Charles C. Murabito, Joanne M. O'Donnell, Christopher J. Dupuis, Josee Florez, Jose C. Meigs, James B. TI Common variants in and near IRS1 and subclinical cardiovascular disease in the Framingham Heart Study SO ATHEROSCLEROSIS LA English DT Article DE IRS1; 2q36.3; Genetic association; Subclinical atherosclerosis; Ankle-brachial index ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; LINKAGE ANALYSIS; RISK; ATHEROSCLEROSIS; LOCI; CALCIFICATION; METAANALYSIS AB Objective: Common variants at the 2q36.3-IRS1 locus are associated with insulin resistance (IR), type 2 diabetes (T2D) and coronary artery disease (CAD) in large-scale association studies. We tested the hypothesis that variants at this locus are associated with subclinical atherosclerosis traits. Methods: We studied 2740 Framingham Heart Study participants (54.9% women; mean age 57.8 years) with measures of coronary artery or abdominal aortic calcium, internal and common carotid intima-media thickness, and ankle-brachial index (ABI). We tested 1) four SNPs previously shown to be associated with IR (rs2972146, rs2943650), T2D (rs2943641) or CAD (rs2943634) and 2) any SNP at 2q36.3-IRS1, for association with subclinical atherosclerosis traits, adjusting for atherosclerosis risk factors. We set type 1 error rate for test 1) as 0.05/5 traits - P < 0.01, and for test 2) as 0.05 divided by the effective number of independent tests, divided by 5 for the number of traits analyzed. Results: We found no association between the four known SNPs and subclinical atherosclerosis, but identified one SNP (rs10167219, r(2) with rs2943634 = 0.07) at 2q36.3 that was significantly associated with ABI (corrected P = 0.009). However, rs10167219 was not associated with ABI (P = 0.70) in 35,404 participants in a published ABI association study. Conclusion: Common variants at the 2q36.3-IRS1 locus were not associated with subclinical atherosclerosis traits in this study which was adequately powered to find associations with moderate effect size. Although IR and T2D may be mechanistically linked to CAD via subclinical atherosclerosis, an alternate mechanism for the IR-T2D-CAD associations at 2q36.3-IRS1 must be postulated. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Lim, Soo; Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Lim, Soo; Hivert, Marie-France; O'Donnell, Christopher J.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Lim, Soo] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Coll Med, Songnam, South Korea. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Hong, Jaeyoung; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hivert, Marie-France] Univ Sherbrooke, Div Endocrinol & Metab, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [White, Charles C.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Murabito, Joanne M.; O'Donnell, Christopher J.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Murabito, Joanne/0000-0002-0192-7516; Dupuis, Josee/0000-0003-2871-3603 FU National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [2R01DK078616, K24 DK080140]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; Boston University Linux Cluster for Genetic Analysis (LinGA); National Institutes of Health National Center for Research Resources Shared Instrumentation Grant [1S10RR163736-01A1] FX This study was funded by the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) 2R01DK078616, K24 DK080140 (Dr. Meigs), the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract Nos. N01-HC-25195, N02-HL-6-4278), and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the National Institutes of Health National Center for Research Resources Shared Instrumentation Grant (1S10RR163736-01A1). The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The sole responsibility for the content of this manuscript lies with the authors. NR 32 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUL PY 2013 VL 229 IS 1 BP 149 EP 154 DI 10.1016/j.atherosclerosis.2013.03.037 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 166XU UT WOS:000320594700024 PM 23659870 ER PT J AU Ge, Y Cheng, S Larson, MG Ghorbani, A Martin, RP Klein, RJ O'Donnell, CJ Vasan, RS Shawe, SY Wang, TJ Cohen, KS AF Ge, Yin Cheng, Susan Larson, Martin G. Ghorbani, Anahita Martin, Roderick P. Klein, Rachael J. O'Donnell, Christopher J. Vasan, Ramachandran S. Shawe, Stanley Y. Wang, Thomas J. Cohen, Kenneth S. TI Circulating CD31+leukocyte frequency is associated with cardiovascular risk factors SO ATHEROSCLEROSIS LA English DT Article DE Epidemiology; CD31; Leukocytes; Endothelial cells; Cardiovascular risk factors ID ENDOTHELIAL PROGENITOR CELLS; ISCHEMIC VASCULAR-DISEASE; CORONARY-HEART-DISEASE; BONE-MARROW; CD31(+) CELLS; VASCULOGENIC CELLS; MONONUCLEAR-CELLS; HUMAN BLOOD; T-CELLS; ANGIOGENESIS AB Objectives: CD31 identifies a heterogeneous population of cells in the blood, consisting of mature leukocytes and platelets, as well as smaller numbers of endothelial and progenitor cells. Because unfractionated CD31+ blood cells have demonstrated angiogenic properties in vivo, we hypothesized that circulating CD31+ cells would be related to the presence of cardiovascular risk factors in humans. Methods and results: We studied 1487 participants, free of cardiovascular disease, from the Framingham Offspring Study. Using anti-human CD31 and CD45 antibodies, distinct CD31+/CD45+ leukocyte populations were enumerated in blood samples by FACS analysis. We used linear regression analyses to investigate the relation of each cell phenotype with cardiovascular risk factors. We identified 3 distinct leukocyte populations: CD31 -, CD31 dim, and CD31 bright cells. Using forward/side scatter analyses, CD31 - and CD31 dim cells mapped to lymphoid gates while CD31 bright cells were monocytoid. In multivariable analyses, higher frequency of CD31 bright cells was associated with older age, male sex, HDL cholesterol, and CRP (all P < 0.01). In contrast, CD31 dim was inversely associated with age, male sex, CRP, and smoking (all P < 0.01). Framingham Risk Score was positively associated with CD31 bright frequency (P = 0.002), and negatively associated with CD31 dim frequency (P = 0.020). Conclusions: CD31+ staining identifies 2 major leukocyte populations, CD31 bright and CD31 dim, which demonstrated significant and opposite associations with cardiovascular risk in humans. Further research is needed to define the biological and potential therapeutic roles of CD31+ subpopulations in vascular disease. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Ge, Yin] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Cheng, Susan; Larson, Martin G.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div, Boston, MA 02115 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ghorbani, Anahita; O'Donnell, Christopher J.; Shawe, Stanley Y.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Martin, Roderick P.] Genzyme Corp, Cambridge, MA USA. [Martin, Roderick P.; Klein, Rachael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Shawe, Stanley Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Cohen, Kenneth S.] Univ Chicago, Med Ctr, Sect Hematol Oncol, Chicago, IL 60637 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. RP Cohen, KS (reprint author), Univ Chicago, Med Ctr, Sect Hematol Oncol, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM tjwang@partners.org; kcohen@medicine.bsd.uchicago.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health; Boston University School of Medicine; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, R01-HL083197, R01-HL93328, K99-HL107642]; Ellison Foundation FX From the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported in part by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), grant R01-HL083197 (TJW), R01-HL93328 (RSV), and K99-HL107642 (SC). Dr. Cheng is supported in part by a grant from the Ellison Foundation. NR 33 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUL PY 2013 VL 229 IS 1 BP 228 EP 233 DI 10.1016/j.atherosclerosis.2013.04.017 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 166XU UT WOS:000320594700037 PM 23701996 ER PT J AU Trinh, QD AF Quoc-Dien Trinh TI Understanding the way we think SO BJU INTERNATIONAL LA English DT Editorial Material ID PROSTATE-CANCER; UROLOGISTS; CARE C1 [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. [Quoc-Dien Trinh] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2013 VL 112 IS 2 BP 157 EP 157 DI 10.1111/bju.12273 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 171LN UT WOS:000320930200022 PM 23795781 ER PT J AU Wirth, GJ Psutka, SP Chapin, BF Wu, SL Wu, CL Dahl, DM AF Wirth, Gregory J. Psutka, Sarah P. Chapin, Brian F. Wu, Shulin Wu, Chin-Lee Dahl, Douglas M. TI Midterm oncological outcomes of laparoscopic vs open radical prostatectomy (RP) SO BJU INTERNATIONAL LA English DT Article DE prostatectomy; prostatic neoplasms; prostate-specific antigen; recurrence ID EXPERIENCE AB Objective To compare the midterm risks of biochemical recurrence (BCR) and salvage radiation therapy (SRT) after laparoscopic (LRP) and open retropubic radical prostatectomy (RRP). Strong evidence that these techniques are comparable to the gold standard' of open RRP is lacking, as most comparative studies are limited by short follow-up or rely on historical controls. Patients and Methods We studied 1000 consecutive patients concurrently treated by either LRP or RRP between 2001 and 2005. LRPs were performed by a single surgeon and RRP by four surgeons. Primary outcomes were BCR and SRT. Survival analysis included relevant clinical and pathological variables. Results Of 844 included patients, 244 underwent LRP and 600 RRP. Clinical and pathological characteristics were similar in both groups. Most patients had Gleason 6 tumours (68%) and pT2 disease (86%). The median follow-up was 6.1 years and median time to recurrence 3.4 years. Overall, BCR occurred in 14% of patients: 13.1% after LRP and 14.7% after RRP. SRT was performed in 10.7% of patients both after LRP and RRP. In uni- and multivariate Cox regression models, surgical technique was not a significant predictor of BCR or SRT. Conclusion Our results suggest that in high-volume centres, LRP provides equivalent oncological control to RRP. C1 [Wirth, Gregory J.; Psutka, Sarah P.; Chapin, Brian F.; Dahl, Douglas M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Wu, Shulin; Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dahl, DM (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM ddahl@partners.org OI Wirth, Gregory J./0000-0003-0636-3438 FU Swiss Cancer League [KLS-02593-02-2010] FX This work was supported in part through a research grant to G.J.W. (Swiss Cancer League grant no. KLS-02593-02-2010). The authors thank Kevin McLaughlin for the logistical support. NR 14 TC 5 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2013 VL 112 IS 2 BP 190 EP 197 DI 10.1111/bju.12085 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 171LN UT WOS:000320930200034 PM 23601185 ER PT J AU Trinh, VQ Trinh, QD Tian, Z Hu, JC Shariat, SF Perrotte, P Karakiewicz, PI Sun, M AF Trinh, Vincent Q. Quoc-Dien Trinh Tian, Zhe Hu, Jim C. Shariat, Shahrokh F. Perrotte, Paul Karakiewicz, Pierre I. Sun, Maxine TI In-hospital mortality and failure-to-rescue rates after radical cystectomy SO BJU INTERNATIONAL LA English DT Article DE cystectomy; urinary bladder neoplasms; postoperative complications; failure to rescue; Nationwide Inpatient Sample ID INVASIVE BLADDER-CANCER; COMPLICATIONS; SURGERY; VOLUME; IMPACT; COMORBIDITY; VALIDATION; MORBIDITY; OUTCOMES AB Objective To show the underlying variability in peri-operative mortality after radical cystectomy (RC) by analysing failure-to-rescue (FTR) rates, i.e. deaths after complications. Materials and Methods Patients undergoing RC for non-metastatic bladder cancer (BCa) were identified from the Nationwide Inpatient Sample, 1999-2009, resulting in a weighted estimate of 79972 patients. The FTR rates were assessed according to patient and hospital characteristics, as well as complication type. Generalized linear regression analyses were performed. Results Overall, 26740 patients had a complication, corresponding to a FTR rate of 5.5%. Septicaemia (odds ratio [OR]: 13.41, P < 0.001) and cardiac (OR: 3.97, P < 0.001), wound-related (OR: 2.12, P < 0.001), genitourinary (OR: 1.62, P = 0.045) and haematological (OR: 1.78, P = 0.008) complications were associated with FTR. Older age (OR: 1.05, P < 0.001), increasing comorbidities (OR: 1.33, P < 0.001), Medicare (OR: 1.52, P = 0.016), and Medicaid insurance status (OR: 2.10, P = 0.029) were associated with higher odds of FTR. Conversely, increasing hospital volume (OR: 0.992, P = 0.014) reduced the odds of FTR. Conclusions Whereas both patient and hospital characteristics were associated with increased odds of FTR, the occurrence of septicaemia and cardiac complications were the most strongly associated with a higher risk of in-hospital mortality. C1 [Trinh, Vincent Q.] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Trinh, Vincent Q.; Tian, Zhe; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Shariat, Shahrokh F.; Perrotte, Paul] Cornell Univ, Dept Urol, Weill Med Coll, New York, NY 10021 USA. [Karakiewicz, Pierre I.] Univ Montreal, Dept Urol, Ctr Hlth, Montreal, PQ, Canada. RP Trinh, VQ (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM quochuytrinh@gmail.com FU University of Montreal Health Centre Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX Pierre I. Karakiewicz was partially supported by the University of Montreal Health Centre Urology Specialists, Fonds de la Recherche en Sante du Quebec, The University of Montreal Department of Surgery and the University of Montreal Health Centre (CHUM) Foundation. NR 25 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2013 VL 112 IS 2 BP E20 EP E27 DI 10.1111/bju.12214 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 171LN UT WOS:000320930200003 PM 23795794 ER PT J AU Christenhusz, MJM Govaerts, R David, JC Hall, T Borland, K Roberts, PS Tuomisto, A Buerki, S Chase, MW Fay, MF AF Christenhusz, Maarten J. M. Govaerts, Rafael David, John C. Hall, Tony Borland, Katherine Roberts, Penelope S. Tuomisto, Anne Buerki, Sven Chase, Mark W. Fay, Michael F. TI Tiptoe through the tulips - cultural history, molecular phylogenetics and classification of Tulipa (Liliaceae) SO BOTANICAL JOURNAL OF THE LINNEAN SOCIETY LA English DT Review DE nomenclature; systematics; tulip mania; typification ID GENUS TULIPA; INFRAGENERIC CLASSIFICATION; ERIOSTEMONES LILIACEAE; SPECIES RELATIONSHIPS; CHROMOSOME VARIATION; CHLOROPLAST DNA; SYSTEMATICS; SEQUENCES; LILIALES; REGIONS AB Tulipa (tulips; Liliaceae) is a genus of geophytes comprising c. 76 species, occurring from southwestern Europe and North Africa to Central Asia. The taxonomy and classification of the genus have been contentious in the past. We investigated the phylogenetic relationships in the genus using DNA sequences from five plastid regions (trnL intron and trnL-trnF spacer, rpl16 intron, rps12-rpl20 intergenic spacer and matK) and the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. Amana and Erythronium were used as outgroups. Sequences were obtained from 25 Tulipa taxa representing all major lineages previously identified as distinct and four outgroups (two Amana spp. and two Erythronium spp.). In the combined maximum parsimony analysis, Tulipa was strongly supported as monophyletic and four clearly defined clades in the genus were obtained, although the relationships between them were unclear. In support of previous molecular studies, the results suggest that section Clusianae should be excluded from subgenus Tulipa and accepted at subgeneric rank. Subgenus Eriostemones and subgenus Tulipa (excluding Clusianae) were both strongly supported. Tulipa sprengeri, traditionally placed in subgenus Tulipa, was shown to be a member of Eriostemones. Orithyia, in this study represented by T.uniflora, formed a fourth lineage, also to be treated at subgeneric level. In the Bayesian analysis, the genus Tulipa was strongly supported and the same four lineages (subgenera) were identified. In this case, Orithyia was sister to the rest of the genus (with moderate support) and subgenera Clusianae and Eriostemones together formed a clade with strong support. Original species descriptions and type specimens of as many names as possible were reviewed and, on this basis, a revised checklist with full synonymy, typification and distribution is provided. The status of T.xgesneriana and its synonyms is discussed. All accepted species are classified into the four subgenera supported by our phylogenetic study.(c) 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 172, 280-328. C1 [Christenhusz, Maarten J. M.; Hall, Tony; Buerki, Sven; Chase, Mark W.; Fay, Michael F.] Royal Bot Gardens, Jodrell Lab, Richmond TW9 3DS, Surrey, England. [Govaerts, Rafael] Univ Helsinki, Bot Garden & Herbarium, Finnish Museum Nat Hist, FIN-00014 Helsinki, Finland. [Govaerts, Rafael] Royal Bot Gardens, Herbarium, Richmond TW9 3AE, Surrey, England. [David, John C.] RHS Garden, Royal Hort Soc, Dept Sci, Woking GU23 6QB, Surrey, England. [Borland, Katherine; Roberts, Penelope S.] Smith Coll, Northampton, MA 01063 USA. [Roberts, Penelope S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tuomisto, Anne] Regents Pk, London NW1 4NR, England. [Chase, Mark W.] Univ Western Australia, Sch Plant Biol, Crawley, WA 6009, Australia. RP Christenhusz, MJM (reprint author), Royal Bot Gardens, Jodrell Lab, Richmond TW9 3DS, Surrey, England. EM m.christenhusz@kew.org RI Buerki, Sven/A-8305-2012; Chase, Mark /A-6642-2011; Christenhusz, Maarten/D-5900-2011; Buerki, Sven/F-6008-2012; Roberts, Peter/J-8535-2016; Fay, Michael /G-4741-2010 OI Fay, Michael /0000-0003-3491-9093 FU Muriel Kohn Pokross Travelling Fellowship; Howard Hughes III Internship Fund of Smith College, Massachusetts FX We thank Richard Wilford and Mehdi Zarrei for useful discussions about tulips, and Richard and his colleagues in the Alpine Nursery at Kew for maintaining the collections of tulips that were the basis of this study. We thank Natalia Ostromenskaya for permission to reproduce her photograph of T. uniflora (Fig. 2C) and the Linnean Society for permission to reproduce an image of the type specimen of T. xgesneriana (Fig. 3). Additionally we thank curators of BEI, BM, BRNM, COI, K, M, MPU, PRC and WU for access to material or sending scans of relevant specimens. We also wish to thank the Muriel Kohn Pokross Travelling Fellowship and the Howard Hughes III Internship Fund of Smith College, Massachusetts, for providing financial support to K.B. and P.S.R. NR 127 TC 18 Z9 19 U1 3 U2 45 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0024-4074 J9 BOT J LINN SOC JI Bot. J. Linnean Soc. PD JUL PY 2013 VL 172 IS 3 BP 280 EP 328 DI 10.1111/boj.12061 PG 49 WC Plant Sciences SC Plant Sciences GA 166KB UT WOS:000320552200003 ER PT J AU Sepulcre, J Sabuncu, MR Becker, A Sperling, R Johnson, KA AF Sepulcre, Jorge Sabuncu, Mert R. Becker, Alex Sperling, Reisa Johnson, Keith A. TI In vivo characterization of the early states of the amyloid-beta network SO BRAIN LA English DT Article DE Alzheimer's disease; network; amyloid; graph theory; early stages ID MILD COGNITIVE IMPAIRMENT; EARLY ALZHEIMERS-DISEASE; PITTSBURGH COMPOUND-B; INTRINSIC FUNCTIONAL CONNECTIVITY; COMPLEX BRAIN NETWORKS; RESTING HUMAN BRAIN; NEUROFIBRILLARY TANGLES; CEREBRAL-CORTEX; A-BETA; NEURITIC PLAQUES AB Alzheimer's disease is a neurodegenerative disease that is associated with the abnormal accumulation of amyloid-beta. Much is known about regional brain atrophy in Alzheimer's disease, yet our knowledge about the network nature of Alzheimer's disease-associated amyloid-beta accumulation is limited. We use stepwise connectivity analysis of Pittsburgh Compound B positron emission tomography images to reveal the network properties of amyloid-beta deposits in normal elderly subjects and clinical patients with Alzheimer's disease. We found that amyloid-beta accumulation in the medial temporal lobe is associated with accumulation in cortical regions such as orbitofrontal, lateral temporal and precuneus/posterior cingulate cortices in Alzheimer's disease. In normal subjects, there was a predominant association between amyloid-beta deposits in the hippocampus and the midline prefrontal/orbitofrontal regions, even in those with very low amyloid-beta burden. Moreover, the orbitofrontal cortex, amygdala nucleus and hippocampus exhibit hub properties in the amyloid-beta network that may be critical to understanding the putative spreading mechanisms of Alzheimer's disease pathology in early stages. C1 [Sepulcre, Jorge; Becker, Alex; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Sepulcre, Jorge; Becker, Alex; Sperling, Reisa; Johnson, Keith A.] Harvard Univ, Sch Med, Boston, MA USA. [Sepulcre, Jorge; Sabuncu, Mert R.; Sperling, Reisa] Athinioula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Sperling, Reisa; Johnson, Keith A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sperling, Reisa; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sepulcre, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM sepulcre@nmr.mgh.harvard.edu FU US National Institute of Health (NIH) [K25EB013649-01, R01-AG027435-S1, P01-AG036694, P50-AG00513421]; Alzheimer's Association [NIRG-11-205690, IIRG-06-32444, ZEN-10-174210] FX This research was supported by grants from the US National Institute of Health (NIH) (K25EB013649-01 to M. R. S.; R01-AG027435-S1 to R. A. S. and K.A.J.; Harvard Aging Brain Study: P01-AG036694 to R. A. S and K.A.J.; Massachusetts ADRC: P50-AG00513421 to K.A.J. and R. A. S.) and Alzheimer's Association (NIRG-11-205690 to J.S.; IIRG-06-32444 to R. A. S. and K.A.J.; ZEN-10-174210 to K.A.J.). NR 110 TC 25 Z9 25 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2013 VL 136 BP 2239 EP 2252 DI 10.1093/brain/awt146 PN 7 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 173EF UT WOS:000321060200028 PM 23801740 ER PT J AU Peyre, M Clermont-Taranchon, E Stemmer-Rachamimov, A Kalamarides, M AF Peyre, Matthieu Clermont-Taranchon, Estelle Stemmer-Rachamimov, Anat Kalamarides, Michel TI Miniaturized Handheld Confocal Microscopy Identifies Focal Brain Invasion in a Mouse Model of Aggressive Meningioma SO BRAIN PATHOLOGY LA English DT Article DE brain neoplasm; invasion; meningioma; MGS; mouse model; multimodal confocal imaging ID 5-AMINOLEVULINIC ACID; LASER ENDOMICROSCOPY; BARRETTS-ESOPHAGUS; INDOCYANINE GREEN; FLUORESCENCE; RECURRENCE; NEOPLASIA; RESECTION; SURGERY; TRIAL AB Invasion of the brain parenchyma by a meningioma classified by histological criteria as World Health Organization (WHO) grade I meningioma, implies that the tumor has greater likelihood of recurrence and a biological behavior similar to the more aggressive WHO grade II meningiomas. It is therefore important to detect microscopic foci of brain invasion during surgery in order to maximize the resection and/or adapt imaging follow-up. In this study, we tested the sensitivity of two handheld confocal imaging devices to detect foci of brain invasion in two types of meningioma mouse models: in a genetically engineered mouse model and in a syngeneic xenograft model. Confocal imaging offered precise images of meningothelial and fibroblastic mouse meningiomas as well as malignant meningiomas, which corresponded exactly to the pathological findings. Imaging showed a sharp definition of the brain-tumor interface and enabled identification of embedded nerves and vessels. Importantly, in both mouse models used in this study, extension of tumor along Virchow-Robin spaces into adjacent brain was detected by imaging. In conclusion, this novel technique, following validation in clinical trials, may open new possibilities for use in operating rooms to influence both decision making during the surgery and planning for additional treatments. C1 [Peyre, Matthieu; Kalamarides, Michel] Hop Beaujon, AP HP, Serv Neurochirurg, F-92110 Clichy, France. [Peyre, Matthieu; Clermont-Taranchon, Estelle; Kalamarides, Michel] Univ Sorbonne Paris Cite, Paris, France. [Peyre, Matthieu; Clermont-Taranchon, Estelle; Kalamarides, Michel] Fdn Jean Dausset, Unite Inserm U674, Paris, France. [Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA USA. RP Kalamarides, M (reprint author), Hop Beaujon, APHP, Dept Neurosurg, 100 Bvd Gen Leclerc, F-92110 Clichy, France. EM michel.kalamarides@bjn.aphp.fr NR 19 TC 7 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2013 VL 23 IS 4 BP 371 EP 377 DI 10.1111/bpa.12039 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 164CH UT WOS:000320385900002 PM 23356716 ER PT J AU Ansbaugh, N Shannon, J Mori, M Farris, PE Garzotto, M AF Ansbaugh, Nathan Shannon, Jackilen Mori, Motomi Farris, Paige E. Garzotto, Mark TI Agent Orange as a risk factor for high-grade prostate cancer SO CANCER LA English DT Article DE prostatic neoplasms; urology; Agent Orange; risk factors; veterans ID VIETNAM-WAR; VETERANS; MORTALITY; EXPOSURE AB BACKGROUND Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa) (Gleason score 7) on biopsy in a US Veteran cohort. METHODS Risk factors included clinicodemographic and laboratory data from veterans who were referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa) (Gleason score 6) in biopsy specimens. Risk among AOe veterans relative to unexposed veterans was estimated using multivariate logistic regression. Separate models were used to determine whether AOe was associated with an increased risk of PCa, HGPCa, or LGPCa. RESULTS Of 2720 veterans who underwent biopsy, PCa was diagnosed in 896 veterans (32.9%), and 459 veterans (16.9%) had HGPCa. AOe was associated with a 52% increase in the overall risk of detecting PCa (adjusted odds ratio, 1.52; 95% confidence interval, 1.07-2.13). AOe did not confer an increase in the risk of LGPCa (adjusted odds ratio, 1.24; 95% confidence interval, 0.81-1.91), although a 75% increase in the risk of HGPCa was observed (adjusted odds ratio, 1.75; 95% confidence interval, 1.12-2.74). AOe was associated with a 2.1-fold increase (95% confidence interval, 1.22-3.62; P < .01) in the risk of detecting PCa with a Gleason score 8. CONCLUSIONS The current results indicated that an increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men who undergo an initial prostate biopsy. These findings may aid in improved PCa screening for Vietnam-era veterans. Cancer 2013;119:2399-2404. (c) 2013 American Cancer Society. C1 [Ansbaugh, Nathan; Shannon, Jackilen] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Shannon, Jackilen; Farris, Paige E.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. [Shannon, Jackilen; Garzotto, Mark] Portland VA Med Ctr, Div Urol, Portland, OR USA. [Shannon, Jackilen; Mori, Motomi; Garzotto, Mark] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Garzotto, Mark] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97201 USA. [Garzotto, Mark] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA. RP Garzotto, M (reprint author), 3710 SW US Vet Hosp Rd P3GU, Portland, OR 97239 USA. EM mark.garzotto@va.gov FU NCI NIH HHS [P30 CA069533] NR 13 TC 8 Z9 9 U1 0 U2 19 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 JUL 1 PY 2013 VL 119 IS 13 BP 2399 EP 2404 DI 10.1002/cncr.27941 PG 6 WC Oncology SC Oncology GA 165FT UT WOS:000320469400009 PM 23670242 ER PT J AU Musuuza, JS Sherman, ME Knudsen, KJ Sweeney, HA Tyler, CV Koroukian, SM AF Musuuza, Jackson S. Sherman, Marion E. Knudsen, Kraig J. Sweeney, Helen Anne Tyler, Carl V. Koroukian, Siran M. TI Analyzing excess mortality from cancer among individuals with mental illness SO CANCER LA English DT Article DE mental illness; excess mortality; all-cancer mortality; site-specific cancer mortality ID OHIO MEDICAID POPULATION; RENAL-CELL CARCINOMA; CIGARETTE-SMOKING; BREAST-CANCER; UNITED-STATES; LUNG-CANCER; FOLLOW-UP; DISORDERS; RISK; SCHIZOPHRENIA AB BACKGROUND The objective was to compare patterns of site-specific cancer mortality in a population of individuals with and without mental illness. METHODS This was a cross-sectional, population-based study using a linked data set comprised of death certificate data for the state of Ohio for the years 2004-2007 and data from the publicly funded mental health system in Ohio. Decedents with mental illness were those identified concomitantly in both data sets. We used age-adjusted standardized mortality ratios (SMRs) in race- and sex-specific person-year strata to estimate excess deaths for each of the anatomic cancer sites. RESULTS Overall, there was excess mortality from cancer associated with having mental illness in all the race/sex strata: SMR, 2.16 (95% CI, 1.85-2.50) for black men; 2.63 (2.31-2.98) for black women; 3.89 (3.61-4.19) for nonblack men; and 3.34 (3.13-3.57) for nonblack women. In all the race/sex strata except for black women, the highest SMR was observed for laryngeal cancer, 3.94 (1.45-8.75) in black men and 6.51 (3.86-10.35) and 6.87 (3.01-13.60) in nonblack men and women, respectively. The next highest SMRs were noted for hepatobiliary cancer and cancer of the urinary tract in all race/sex strata, except for black men. CONCLUSIONS Compared with the general population in Ohio, individuals with mental illness experienced excess mortality from most cancers, possibly explained by a higher prevalence of smoking, substance abuse, and chronic hepatitis B or C infections in individuals with mental illness. Excess mortality could also reflect late-stage diagnosis and receipt of inadequate treatment. Cancer 2013;119:2469-2476. (c) 2013 American Cancer Society. C1 [Musuuza, Jackson S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Sherman, Marion E.] Joint Ambulatory Care Ctr, US Dept Vet Affairs, Pensacola, FL USA. [Knudsen, Kraig J.; Sweeney, Helen Anne] Ohio Dept Mental Hlth, Columbus, OH USA. [Tyler, Carl V.] Cleveland Clin, Cleveland, OH 44106 USA. [Tyler, Carl V.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Koroukian, Siran M.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Sch Med, Cleveland, OH 44106 USA. RP Koroukian, SM (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Sch Med, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM skoroukian@case.edu FU Ohio Department of Mental Health; Clinical and Translational Science Collaborative of Cleveland from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health [UL1TR000439]; NIH Roadmap for Medical Research FX Drs. Siran M. Koroukian and Jackson Musuuza were supported by a grant from the Ohio Department of Mental Health. Dr. Siran M. Koroukian is also supported by the Clinical and Translational Science Collaborative of Cleveland, UL1TR000439, from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 45 TC 8 Z9 8 U1 1 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 JUL 1 PY 2013 VL 119 IS 13 BP 2469 EP 2476 DI 10.1002/cncr.28091 PG 8 WC Oncology SC Oncology GA 165FT UT WOS:000320469400018 PM 23585241 ER PT J AU Reiter, RJ Tan, DX Manchester, LC Korkmaz, A Fuentes-Broto, L Hardman, WE Rosales-Corral, SA Qi, WB AF Reiter, Russel J. Tan, Dun-Xian Manchester, Lucien C. Korkmaz, Ahmet Fuentes-Broto, Lorena Hardman, W. Elaine Rosales-Corral, Sergio A. Qi, Wenbo TI A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice SO CANCER INVESTIGATION LA English DT Article DE LNCaP cells; Prostate cancer; Walnuts; F-2-isoprostanes ID N-3 FATTY-ACIDS; BREAST-CANCER; GAMMA-TOCOPHEROL; VITAMIN-E; IN-VIVO; ENDOTHELIAL FUNCTION; CELL-PROLIFERATION; LIPID-PEROXIDATION; MEDITERRANEAN DIET; ELLAGIC ACID AB It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet. C1 [Reiter, Russel J.; Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Rosales-Corral, Sergio A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Hardman, W. Elaine] Marshall Univ, Sch Med, Dept Biochem & Microbiol, Huntington, WV USA. [Qi, Wenbo] Vet Adm Hosp, San Antonio, TX USA. RP Reiter, RJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM reiter@uthscsa.edu RI Fuentes-Broto, Lorena/D-2773-2009 OI Fuentes-Broto, Lorena/0000-0003-2656-6750 FU American Institute for Cancer Research [09A073] FX This work was supported by a grant from the American Institute for Cancer Research (grant #09A073). NR 66 TC 13 Z9 14 U1 0 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD JUL PY 2013 VL 31 IS 6 BP 365 EP 373 DI 10.3109/07357907.2013.800095 PG 9 WC Oncology SC Oncology GA 170PZ UT WOS:000320866800001 PM 23758186 ER PT J AU Hedgire, SS Sainani, NI McDermott, S Hahn, PF Harisinghani, MG AF Hedgire, Sandeep S. Sainani, Nisha I. McDermott, Shaunagh Hahn, Peter F. Harisinghani, Mukesh G. TI Mono-belly and beyond: spectrum of imaging manifestations of EBV infection in the abdomen SO CLINICAL IMAGING LA English DT Article DE Epstein-Barr virus (EBV); Infectious mononucleosis; Abdomen; Lymphoma ID BARR-VIRUS INFECTION; MONONUCLEOSIS HEPATITIS; SPLENIC INFARCTION; INVOLVEMENT; DIAGNOSIS; GASTRITIS; DISEASE; CANCERS; PATIENT; ADULT AB Epstein-Barr virus (EBV) is a DNA virus from the herpes virus group affecting only humans. More than 90% adults are infected by the virus, but very few ever have symptoms. Within the abdomen, both solid and hollow viscera can be involved in symptomatic disease. Awareness of the spectrum of imaging findings, high index of suspicion, and appropriate clinical and laboratory information can help in the early and accurate diagnosis in these cases. (c) 2013 Elsevier Inc. All rights reserved. C1 [Hedgire, Sandeep S.; McDermott, Shaunagh; Hahn, Peter F.; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Sainani, Nisha I.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Hedgire, SS (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM Hedgire.Sandeep@mgh.harvard.edu NR 36 TC 0 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 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JUL-AUG PY 2013 VL 37 IS 4 BP 711 EP 717 DI 10.1016/j.clinimag.2012.10.003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172TZ UT WOS:000321029100016 PM 23317894 ER PT J AU Tirumani, H Assiri, YI Brimo, F Tsatoumas, M Reinhold, C AF Tirumani, Harsha Assiri, Yahia Ibrahim Brimo, Fadi Tsatoumas, Maria Reinhold, Caroline TI Diffusion-weighted MR imaging of mucin-rich mucinous tubular and spindle cell carcinoma of the kidney: a case report SO CLINICAL IMAGING LA English DT Article DE Mucinous tubular and spindle cell carcinoma; Renal cell carcinoma; MRI; Diffusion-weighted MR imaging ID RENAL MASSES; PAPILLARY; FEATURES; SUBTYPES; RARE AB Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare indolent subtype of renal cell carcinoma, which has variable magnetic resonance (MR) imaging features due to histomorphologic diversity. Diffusion-weighted MR imaging has shown its ability to differentiate benign and malignant renal neoplasms in some recent studies and can be a useful adjunct to routine MR sequences in ambiguous cases. We present a histopathology proven case of MTSCC highlighting the role of diffusion-weighted imaging in guiding the surgical management. (C) 2013 Elsevier Inc. All rights reserved. C1 [Tirumani, Harsha] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Imaging,Dana Farber Canc, Boston, MA 02215 USA. [Assiri, Yahia Ibrahim; Tsatoumas, Maria; Reinhold, Caroline] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Dept Diagnost Radiol, Montreal, PQ H3G 1A4, Canada. [Brimo, Fadi] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Dept Pathol, Montreal, PQ H3G 1A4, Canada. RP Tirumani, H (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Imaging,Dana Farber Canc, Boston, MA 02215 USA. EM tirumani.sreeharsha@gmail.com NR 12 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 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JUL-AUG PY 2013 VL 37 IS 4 BP 775 EP 777 DI 10.1016/j.clinimag.2013.01.017 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172TZ UT WOS:000321029100031 ER PT J AU Souza, FF de Angelo, M O'Regan, K Jagannathan, J Krajewski, K Ramaiya, N AF Souza, Frederico F. de Angelo, Mauricio O'Regan, Kevin Jagannathan, Jyothi Krajewski, Katherine Ramaiya, Nikhil TI Malignant primary chest wall neoplasms: a pictorial review of imaging findings (vol 37, pg 8, 2013) SO CLINICAL IMAGING LA English DT Correction C1 [Souza, Frederico F.; de Angelo, Mauricio] Univ Mississippi, Med Ctr, Dept Radiol, Jackson, MS 39216 USA. [O'Regan, Kevin; Jagannathan, Jyothi; Krajewski, Katherine; Ramaiya, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Souza, FF (reprint author), Univ Mississippi, Med Ctr, Dept Radiol, Jackson, MS 39216 USA. NR 1 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 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JUL-AUG PY 2013 VL 37 IS 4 BP 808 EP 808 DI 10.1016/j.clinimag.2013.01.001 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172TZ UT WOS:000321029100040 ER PT J AU Hartmann, AS Greenberg, JL Wilhelm, S AF Hartmann, Andrea S. Greenberg, Jennifer L. Wilhelm, Sabine TI The relationship between anorexia nervosa and body dysmorphic disorder SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE Anorexia nervosa; Body dysmorphic disorder; Classification; Eating disorders; Body image dissatisfaction ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; EMOTION RECOGNITION DEFICITS; RANDOMIZED CONTROLLED-TRIAL; POPULATION-BASED SURVEY; 10-YEAR FOLLOW-UP; LONG-TERM COURSE; EATING-DISORDERS; COMMITMENT THERAPY; CLINICAL-FEATURES AB Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are severe body image disorders that highly impair individuals in their daily functioning. They are discrete but overlapping nosological entities. In this review, we examine similarities between AN and BDD with regard to clinical, personality and demographic aspects, such as comorbidity, phenomenology, and treatment outcome. The review suggests that the two disorders are highly comorbid, and show similar ages of onset, illness trajectories, and comparable clinical and personality characteristics. However, important differences emerge in their responsiveness to psychosocial and psychopharmacological treatment, which are discussed. Clinical implications of these findings are summarized and directions for future research are delineated, with a focus on how current treatment components from each disorder may inform new interventions for both disorders. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hartmann, Andrea S.] Univ Osnabruck, D-49069 Osnabruck, Germany. [Greenberg, Jennifer L.; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, Jennifer L.; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. RP Hartmann, AS (reprint author), Univ Osnabruck, Dept Human Sci, Inst Psychol, Knollstr 15, D-49069 Osnabruck, Germany. EM andrea.hartmann@uni-osnabrueck.de NR 193 TC 15 Z9 16 U1 9 U2 61 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD JUL PY 2013 VL 33 IS 5 BP 675 EP 685 DI 10.1016/j.cpr.2013.04.002 PG 11 WC Psychology, Clinical SC Psychology GA 171EJ UT WOS:000320907600004 PM 23685673 ER PT J AU Yomogida, K Chou, YK Chu, CQ AF Yomogida, Kentaro Chou, Yuan K. Chu, Cong-Qiu TI Superantigens induce IL-17 production from polarized Th1 clones SO CYTOKINE LA English DT Article DE Superantigen; Th1; Th17; MOG(35-55) ID MYELIN BASIC-PROTEIN; BACTERIAL SUPERANTIGENS; T-CELLS; DIFFERENTIATION; SPECIFICITY; ACTIVATION; DISEASES AB Differentiation of naive CD4(+) T cells has been considered to be an irreversible event and, in particular, the plasticity is believed to be completely lost in Th1 subset in vitro after multiple stimulations. However, here we demonstrate that highly polarized myelin oligodendrocyte glycoprotein (MOG)- and herpes simples virus-specific Th1 clones were still capable of producing IL-17 upon superantigen stimulation. Anti-MHC class-II and anti-TCR alpha beta chains partially blocked superantigen-induced IL-17 production. These findings suggest that fully differentiated Th1 cells still have capability to produce cytokines of other Th subsets and production of IL-17 by MOG-specific Th1 cells may have implication in initiation and/or exacerbation of neurological autoimmune diseases. Published by Elsevier Ltd. C1 Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Chu, CQ (reprint author), 3181 SW Sam Jackson Pk Rd,OP09, Portland, OR 97239 USA. EM chuc@ohsu.edu FU NIH [AR055254]; Portland VA Medical Center FX This work was supported by a grant from NIH to CQC (AR055254) and Portland VA Medical Center. NR 14 TC 3 Z9 3 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL PY 2013 VL 63 IS 1 BP 6 EP 9 DI 10.1016/j.cyto.2013.04.015 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 172CG UT WOS:000320977000002 PM 23664273 ER PT J AU Rhodes, CJ White, MF Leahy, JL Kahn, SE AF Rhodes, Christopher J. White, Morris F. Leahy, John L. Kahn, Steven E. TI Direct Autocrine Action of Insulin on beta-Cells: Does It Make Physiological Sense? SO DIABETES LA English DT Article ID PREPROINSULIN MESSENGER-RNA; PROINSULIN BIOSYNTHESIS; IRS-2 EXPRESSION; FEEDBACK INHIBITION; PANCREATIC INSULIN; DIABETES-MELLITUS; PORTAL-VEIN; GLUCOSE; RECEPTOR; SECRETION AB In recent years there has been a growing interest in the possibility of a direct autocrine effect of insulin on the pancreatic beta-cell. Indeed, there have been numerous intriguing articles and several eloquent reviews written on the subject (1-3); however, the concept is still controversial. Although many in vitro experiments, a few transgenic mouse studies, and some human investigations would be supportive of the notion, there exist different insights, other studies, and circumstantial evidence that question the concept. Therefore, the idea of autocrine action of insulin remains a conundrum. Here we outline a series of thoughts, insights, and alternative interpretations of the available experimental evidence. We ask, how convincing are these, and what are the confusing issues? We agree that there is a clear contribution of certain downstream elements in the insulin signaling pathway for beta-cell function and survival, but the question of whether insulin itself is actually the physiologically relevant ligand that triggers this signal transduction remains unsettled. C1 [Rhodes, Christopher J.] Univ Chicago, Dept Med, Kovler Diabet Ctr, Chicago, IL 60637 USA. [White, Morris F.] Harvard Univ, Sch Med, Dept Med, Div Endocrinol,Boston Childrens Hosp, Boston, MA USA. [Leahy, John L.] Univ Vermont, Dept Med, Div Endocrinol Diabet & Metab, Colchester, VT USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Rhodes, CJ (reprint author), Univ Chicago, Dept Med, Kovler Diabet Ctr, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM cjrhodes@uchicago.edu FU National Institutes of Health [DK-055267, DK-050610, DK-075998, DK-017047, DK-056818, DK-038712]; Department of Veterans Affairs FX This work was supported by National Institutes of Health grants DK-055267 (C.J.R.), DK-050610 (C.J.R.), DK-075998 (S.E.K.), DK-017047 (S.E.K.), DK-056818 (J.L.L.), and DK-038712 (M.F.W.) and the Department of Veterans Affairs (S.E.K.). NR 64 TC 27 Z9 28 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2013 VL 62 IS 7 BP 2157 EP 2163 DI 10.2337/db13-0246 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173KA UT WOS:000321077200001 PM 23801714 ER PT J AU Kahn, SE AF Kahn, Steven E. TI Incretin Therapy and Islet Pathology: A Time for Caution SO DIABETES LA English DT Editorial Material ID GLUCAGON-LIKE PEPTIDE-1; GASTRIC BYPASS-SURGERY; BETA-CELL APOPTOSIS; ACUTE-PANCREATITIS; GLP-1 ANALOG; RISK; GLUCOSE; HYPERPLASIA; SECRETION; HUMANS C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU BLRD VA [I01 BX001060]; NIDDK NIH HHS [P30 DK017047] NR 25 TC 39 Z9 39 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2013 VL 62 IS 7 BP 2178 EP 2180 DI 10.2337/db13-0520 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173KA UT WOS:000321077200005 PM 23596147 ER PT J AU Akiyama, M Liew, CW Lu, SS Hu, J Martinez, R Hambro, B Kennedy, RT Kulkarni, RN AF Akiyama, Masaru Liew, Chong Wee Lu, Shusheng Hu, Jiang Martinez, Rachael Hambro, Ben Kennedy, Robert T. Kulkarni, Rohit N. TI X-Box tiliding Protein 1 Is Essential for Insulin Regulation of Pancreatic alpha-Cell Function SO DIABETES LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; DIABETES-MELLITUS; GLUCAGON-SECRETION; TRANSCRIPTION FACTOR; MESSENGER-RNA; BETA-CELLS; ER STRESS; GLUCOSE; XBP1; EXPRESSION AB Patients with type 2 diabetes (T2D) often exhibit hyperglucagonemia despite hyperglycemia, implicating defective alpha-cell function. Although endoplasmic reticulum (ER) stress has been suggested to underlie beta-cell dysfunction in T2D, its role in alpha-cell biology remains unclear. X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR), and its deficiency in beta-cells has been reported to impair insulin secretion, leading to glucose intolerance. To evaluate the role of XBP1 in alpha-cells, we created complementary in vivo (alpha-cell-specific XBP1 knockout [alpha XBPKO] mice) and in vitro (stable XBP1 knockdown alpha-cell line [alpha XBPKD]) models. The alpha XBPKO mice exhibited glucose intolerance, mild insulin resistance, and an inability to suppress glucagon secretion after glucose stimulation. alpha XBPICD cells exhibited activation of inositol-requiring enzyme 1, an upstream activator of XBP1, leading to phosphorylation of Jun NH2-terminal kinase. Interestingly, insulin treatment of alpha XBPICD cells reduced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) (py(896)) and phosphorylation of Akt while enhancing serine phosphorylation (pS(307)) of IRS1. Consequently, the alpha XBPKD cells exhibited blunted suppression of glucagon secretion after insulin treatment in the presence of high glucose. Together, these data indicate that XBP1 deficiency in pancreatic alpha-cells induces altered insulin signaling and dysfunctional glucagon secretion. C1 [Akiyama, Masaru; Liew, Chong Wee; Hu, Jiang; Martinez, Rachael; Hambro, Ben; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. [Akiyama, Masaru; Liew, Chong Wee; Hu, Jiang; Martinez, Rachael; Hambro, Ben; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA USA. [Lu, Shusheng; Kennedy, Robert T.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Lu, Shusheng; Kennedy, Robert T.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Lu, Shusheng] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Kennedy, Robert/G-9095-2016 OI Kennedy, Robert/0000-0003-2447-7471 FU NIB [RO1-DK-67536]; NIH [R37-DK046960, K99-DK090210]; Hiroo Kaneda Research Aid Fund of the Sunstar Foundation of Osaka, Japan FX Some reagents used in this research work were supported by NIB RO1-DK-67536 (R.N.K), NIH R37-DK046960 (R.T.K.), and NIH K99-DK090210 (C.W.). M.A. is the recipient of a Research Fellowship from the Hiroo Kaneda Research Aid Fund of the Sunstar Foundation of Osaka, Japan. NR 50 TC 18 Z9 18 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2013 VL 62 IS 7 BP 2439 EP 2449 DI 10.2337/db12-1747 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173KA UT WOS:000321077200033 PM 23493568 ER PT J AU Spijker, HS Ravelli, RBG Mommaas-Kienhuis, AM van Apeldoorn, AA Engelse, MA Zaldumbide, A Bonner-Weir, S Rabelink, TJ Hoeben, RC Clevers, H Mummery, CL Carlotti, F de Koning, EJP AF Spijker, H. Siebe Ravelli, Raimond B. G. Mommaas-Kienhuis, A. Mieke van Apeldoorn, Aart A. Engelse, Marten A. Zaldumbide, Arnaud Bonner-Weir, Susan Rabelink, Ton J. Hoeben, Rob C. Clevers, Hans Mummery, Christine L. Carlotti, Francoise de Koning, Eelco J. P. TI Conversion of Mature Human beta-Cells Into Glucagon-Producing alpha-Cells SO DIABETES LA English DT Article ID HUMAN PANCREATIC-ISLETS; IN-VITRO; EXPRESSION; LIVER; DIFFERENTIATION; HYPERGLYCEMIA; MICROSCOPY; THERAPY; CONTEXT; TISSUE AB Conversion of one terminally differentiated cell type into another (or transdifferentiation) usually requires the forced expression of key transcription factors. We examined the plasticity of human insulin-producing beta-cells in a model of islet cell aggregate formation. Here, we show that primary human beta-cells can undergo a conversion into glucagon-producing alpha-cells without introduction of any genetic modification. The process occurs within days as revealed by lentivirus-mediated beta-cell lineage tracing. Converted cells are indistinguishable from native alpha-cells based on ultrastructural morphology and maintain their alpha-cell phenotype after transplantation in vivo. Transition of beta-cells into alpha-cells occurs after beta-cell degranulation and is characterized by the presence of beta-cell specific transcription factors Pdx1 and Nkx6.1 in glucagon(+) cells. Finally, we show that lentivirus-mediated knock-down of Arx, a determinant of the alpha-cell lineage, inhibits the conversion. Our findings reveal an unknown plasticity of human adult endocrine cells that can be modulated. This endocrine cell plasticity could have implications for islet development, (patho) physiology, and regeneration. C1 [Spijker, H. Siebe; Engelse, Marten A.; Rabelink, Ton J.; Carlotti, Francoise; de Koning, Eelco J. P.] Leiden Univ, Dept Nephrol, Med Ctr, Leiden, Netherlands. [Ravelli, Raimond B. G.; Mommaas-Kienhuis, A. Mieke; Zaldumbide, Arnaud; Hoeben, Rob C.] Leiden Univ, Dept Mol Cell Biol, Med Ctr, Leiden, Netherlands. [van Apeldoorn, Aart A.] Univ Twente, NL-7500 AE Enschede, Netherlands. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. [Clevers, Hans; de Koning, Eelco J. P.] Hubrecht Inst, Utrecht, Netherlands. [Mummery, Christine L.] Leiden Univ, Dept Anat & Embryol, Med Ctr, Leiden, Netherlands. [de Koning, Eelco J. P.] Leiden Univ, Dept Endocrinol, Med Ctr, Leiden, Netherlands. RP de Koning, EJP (reprint author), Leiden Univ, Dept Nephrol, Med Ctr, Leiden, Netherlands. EM e.dekoning@lumc.nl RI Hoeben, Rob/A-5771-2008; Rabelink, Ton/A-5316-2008; Carlotti, Francoise/H-1060-2014 OI Hoeben, Rob/0000-0001-9443-8377; Rabelink, Ton/0000-0001-6780-5186; FU Dutch Diabetes Research Foundation; Diabetes Cell Therapy Initiative; DON foundation; Bontius Foundation FX This project is supported by the Dutch Diabetes Research Foundation. Additional funding for our laboratory was obtained from the Diabetes Cell Therapy Initiative, the DON foundation, and the Bontius Foundation. NR 31 TC 37 Z9 39 U1 1 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2013 VL 62 IS 7 BP 2471 EP 2480 DI 10.2337/db12-1001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173KA UT WOS:000321077200036 PM 23569174 ER PT J AU Martini, S Nair, V Patel, SR Eichinger, F Nelson, RG Weil, EJ Pezzolesi, MG Krolewski, AS Randolph, A Keller, BJ Werner, T Kretzler, M AF Martini, Sebastian Nair, Viji Patel, Sanjeevkumar R. Eichinger, Felix Nelson, Robert G. Weil, E. Jennifer Pezzolesi, Marcus G. Krolewski, Andrzej S. Randolph, Ann Keller, Benjamin J. Werner, Thomas Kretzler, Matthias TI From Single Nucleotide Polymorphism to Transcriptional Mechanism A Model for FRMD3 in Diabetic Nephropathy SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; BONE MORPHOGENETIC PROTEIN-7; CHRONIC KIDNEY-DISEASE; PROMOTER ANALYSIS; FUNCTIONAL-CHARACTERIZATION; NETWORK ANALYSIS; GENETIC-FACTORS; EXPRESSION; IDENTIFICATION; MELLITUS AB Genome-wide association studies have proven to be highly effective at defining relationships between single nucleotide polymorphisms (SNPs) and clinical phenotypes in complex diseases. Establishing a mechanistic link between a noncoding SNP and the clinical outcome is a significant hurdle in translating associations into biological insight. We demonstrate an approach to assess the functional context of a diabetic nephropathy (DN)-associated SNP located in the promoter region of the gene FRMD3. The approach integrates pathway analyses with transcriptional regulatory pattern-based promoter modeling and allows the identification of a transcriptional framework affected by the DN-associated SNP in the FRMD3 promoter. This framework provides a testable hypothesis for mechanisms of genomic variation and transcriptional regulation in the context of DN. Our model proposes a possible transcriptional link through which the polymorphism in the FRMD3 promoter could influence transcriptional regulation within the bone morphogenetic protein (BMP)-signaling pathway. These findings provide the rationale to interrogate the biological link between FRMD3 and the BMP pathway and serve as an example of functional genomics-based hypothesis generation. C1 [Martini, Sebastian; Nair, Viji; Patel, Sanjeevkumar R.; Eichinger, Felix; Randolph, Ann; Werner, Thomas; Kretzler, Matthias] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Martini, Sebastian; Nair, Viji; Patel, Sanjeevkumar R.; Eichinger, Felix; Randolph, Ann; Werner, Thomas; Kretzler, Matthias] Univ Michigan, Dept Nephrol, Ann Arbor, MI 48109 USA. [Nelson, Robert G.; Weil, E. Jennifer] NIDDK, NIH, Phoenix, AZ USA. [Pezzolesi, Marcus G.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Pezzolesi, Marcus G.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Clin Div, Boston, MA 02215 USA. [Keller, Benjamin J.] Eastern Michigan Univ, Dept Comp Sci, Ypsilanti, MI 48197 USA. [Werner, Thomas] Genomatix Software GmbH, Munich, Germany. RP Kretzler, M (reprint author), Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. EM kretzler@umich.edu FU National Institutes of Health [R01-DK058549, K01-DK090125]; O'Brien Renal Center [P30-DK081943]; National Center for Integrative Bioinformatics [U54-DA021519]; Federal Ministry of Education and Research, Germany [01EX1021L] FX This study was supported in part by National Institutes of Health grants R01-DK058549 to A.S.K. and K01-DK090125 to M.G.P., by the O'Brien Renal Center (P30-DK081943) and the National Center for Integrative Bioinformatics (U54-DA021519) to M.K., and from the Federal Ministry of Education and Research, Germany (01EX1021L) to T.W. NR 47 TC 18 Z9 19 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2013 VL 62 IS 7 BP 2605 EP 2612 DI 10.2337/db12-1416 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173KA UT WOS:000321077200049 PM 23434934 ER PT J AU Rosenstock, J Marx, N Kahn, SE Zinman, B Kastelein, JJ Lachin, JM Bluhmki, E Patel, S Johansen, OE Woerle, HJ AF Rosenstock, Julio Marx, Nikolaus Kahn, Steven E. Zinman, Bernard Kastelein, John J. Lachin, John M. Bluhmki, Erich Patel, Sanjay Johansen, Odd-Erik Woerle, Hans-Juergen TI Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: Rationale for the active-comparator CAROLINA trial SO DIABETES & VASCULAR DISEASE RESEARCH LA English DT Review DE Type 2 diabetes mellitus; cardiovascular disease; oral glucose-lowering agent; dipeptidyl peptidase-4 inhibitor; sulphonylurea ID BLOOD-GLUCOSE CONTROL; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; CORONARY-ARTERY-DISEASE; ALL-CAUSE MORTALITY; MYOCARDIAL-INFARCTION; EUROPEAN-ASSOCIATION; VASCULAR COMPLICATIONS; GLYCEMIC CONTROL; HEART-DISEASE; MELLITUS AB Sulphonylureas (SUs) are widely used glucose-lowering agents in type 2 diabetes mellitus (T2DM) with apparent declining efficacy over time. Concerns have been raised from observational retrospective studies on the cardiovascular (CV) safety of SUs but there are few long-term data on CV outcomes from randomized controlled trials (RCTs) involving the use of this class of agents. Most of the observational studies and registry data are conflicting and vary with study population and methodology used for analyses. To address the SU controversy, we reviewed the recently published literature (until end of the year 2011) to evaluate the impact of SUs on CV outcomes in modern, longer-term (>= 72 weeks) RCTs where they were compared in a head-to-head fashion versus an active comparator or were used as part of a treatment strategy. We identified 15 trials and found no report of an increase in the incidence of CV events with the use of SUs. However, the available data are limited, and, most importantly, there was no adequately powered formal head-to-head CV outcome trial designed to address CV safety. Since SUs are still being advocated as second-line therapy added-on to metformin, as one of several classes, and in certain circumstances first-line therapy in T2DM management, definitive data from a dedicated RCT addressing the CV safety question with SUs would be informative. Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) is such a trial, ongoing since November 2010, and is currently the largest head-to-head CV outcome trial that involves a comparison of a SU (glimepiride) with a dipeptidyl peptidase-4 (DPP-4) inhibitor (linagliptin) and will provide a unique perspective with respect to CV outcomes with these two commonly used agents. C1 [Rosenstock, Julio] Med City, Dallas Diabet & Endocrine Ctr, Dallas, TX USA. [Marx, Nikolaus] Univ Hosp Aachen, Dept Internal Med 1, D-52074 Aachen, Germany. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Dept Med, Seattle, WA USA. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Zinman, Bernard] Univ Toronto, Div Endocrinol, Toronto, ON, Canada. [Kastelein, John J.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Bluhmki, Erich] Boehringer Ingelheim GmbH & Co KG, Biberach, Germany. [Patel, Sanjay] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. [Johansen, Odd-Erik; Woerle, Hans-Juergen] Boehringer Ingelheim KG, Ingelheim, Germany. RP Marx, N (reprint author), Univ Hosp Aachen, Dept Internal Med 1, Pauwelsstr 30, D-52074 Aachen, Germany. EM nmarx@ukaachen.de RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU Boehringer Ingelheim FX This study was supported financially by Boehringer Ingelheim. NR 62 TC 70 Z9 72 U1 2 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1479-1641 J9 DIABETES VASC DIS RE JI Diabetes Vasc. Dis. Res. PD JUL PY 2013 VL 10 IS 4 BP 289 EP 301 DI 10.1177/1479164112475102 PG 13 WC Endocrinology & Metabolism; Peripheral Vascular Disease SC Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 165RX UT WOS:000320502300001 PM 23449634 ER PT J AU Gahete, MD Cordoba-Chacon, J Lin, Q Bruning, JC Kahn, CR Castano, JP Christian, H Luque, RM Kineman, RD AF Gahete, Manuel D. Cordoba-Chacon, Jose Lin, Qing Bruening, Jens C. Kahn, C. Ronald Castano, Justo P. Christian, Helen Luque, Raul M. Kineman, Rhonda D. TI Insulin and IGF-I Inhibit GH Synthesis and Release in Vitro and in Vivo by Separate Mechanisms SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; RAT ANTERIOR-PITUITARY; MESSENGER-RNA LEVELS; HORMONE-SECRETION; GH/IGF-I; METABOLIC FACTORS; BODY-COMPOSITION; GENE-EXPRESSION; OBESE SUBJECTS; SOMATOSTATIN AB IGF-I is considered a primary inhibitor of GH secretion. Insulin may also play an important role in regulating GH levels because insulin, like IGF-I, can suppress GH synthesis and release in primary pituitary cell cultures and insulin is negatively correlated with GH levels in vivo. However, understanding the relative contribution insulin and IGF-I exert on controlling GH secretion has been hampered by the fact that circulating insulin and IGF-I are regulated in parallel and insulin (INSR) and IGF-I (IGFIR) receptors are structurally/functionally related and ubiquitously expressed. To evaluate the separate roles of insulin and IGF-I in directly regulating GH secretion, we used the Cre/loxP system to knock down the INSR and IGFIR in primary mouse pituitary cell cultures and found insulin-mediated suppression of GH is independent of the IGFIR. In addition, pharmacological blockade of intracellular signals in both mouse and baboon cultures revealed insulin requires different pathways from IGF-I to exert a maximal inhibitory effect on GH expression/release. In vivo, somatotrope-specific knockout of INSR (SIRKO) or IGFIR (SIGFRKO) increased GH levels. However, comparison of the pattern of GH release, GH expression, somatotrope morphometry, and pituitary explant sensitivity to acute GHRH challenge in lean SIRKO and SIGFRKO mice strongly suggests the primary role of insulin in vivo is to suppress GH release, whereas IGF-I serves to regulate GH synthesis. Finally, SIRKO and/or SIGFRKO could not prevent high-fat, diet-induced suppression of pituitary GH expression, indicating other factors/tissues are involved in the decline of GH observed with weight gain. (Endocrinology 154: 2410-2420, 2013) C1 [Gahete, Manuel D.; Cordoba-Chacon, Jose; Lin, Qing; Kineman, Rhonda D.] Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. [Gahete, Manuel D.; Cordoba-Chacon, Jose; Lin, Qing; Kineman, Rhonda D.] Univ Illinois, Dept Med, Sect Endocrinol Diabet & Metab, Chicago, IL 60612 USA. [Gahete, Manuel D.; Castano, Justo P.; Luque, Raul M.] Univ Cordoba, Inst Maimonides Invest Biomed Cordoba, Dept Cell Biol Physiol & Immunol, Cordoba 14014, Spain. Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Cordoba 14014, Spain. [Bruening, Jens C.] Max Planck Inst Neurol Res, Inst Genet, Ctr Mol Med Mouse Genet & Metab, D-50924 Cologne, Germany. [Bruening, Jens C.] Univ Hosp, Ctr Endocrinol Diabet & Prevent Med, D-50924 Cologne, Germany. [Kahn, C. Ronald] Joslin Diabet Ctr, Sect Obes & Hormone Act, Boston, MA 02215 USA. [Christian, Helen] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. RP Kineman, RD (reprint author), Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, 820 South Damen Ave,Bldg 11A,Suite 6215,MP151, Chicago, IL 60612 USA. EM kineman@uic.edu RI Castano, Justo P/A-7124-2010; Gahete, Manuel/C-4969-2009; Kineman, Rhonda/H-2221-2011 OI Castano, Justo P/0000-0002-3145-7287; Gahete, Manuel/0000-0002-4578-2179; Kineman, Rhonda/0000-0001-7322-1152 FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development Merit Award [BX001114]; National Institutes of Health [R01DK088133]; "Sara Borrell" Program [CD11/00276]; Ministerios de Educacion y Ciencia e Innovacion [RYC-2007-00186, JC2008-00220, BFU2008-01136/BFI, BFU2010-19300]; Junta de Andalucia [BIO-0139/CTS-5051] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Merit Award BX001114 and National Institutes of Health Grant R01DK088133 (to R.D.K.), "Sara Borrell" Program Grant CD11/00276 (to M.D.G.); Ministerios de Educacion y Ciencia e Innovacion Grants RYC-2007-00186, JC2008-00220, and BFU2008-01136/BFI (to R.M.L.), Grant BFU2010-19300 (to J.P.C.) and Junta de Andalucia Grant BIO-0139/CTS-5051 (to J.P.C.). Centro de Investigacion Biomedica en Red is an initiative of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion (Spain). NR 39 TC 11 Z9 11 U1 3 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2013 VL 154 IS 7 BP 2410 EP 2420 DI 10.1210/en.2013-1261 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EL UT WOS:000320760700019 PM 23671263 ER PT J AU Wang, SL Passias, PG Cui, LB Li, G Yan, M Zhou, HT Wang, C AF Wang, Shenglin Passias, Peter G. Cui, Libin Li, Gang Yan, Ming Zhou, Haitao Wang, Chao TI Does atlantoaxial dislocation influence the subaxial cervical spine? SO EUROPEAN SPINE JOURNAL LA English DT Article DE Atlantoaxial dislocation; Atlas occipitalization; Basilar invagination; Cervical alignment ID RHEUMATOID-ARTHRITIS; ALIGNMENT; FUSION AB Previous studies have reported that the alignments of the occipital-cervical and subaxial spine were closely interrelated in asymptomatic individuals; however, none have focused on a population with atlantoaxial dislocation. From 2007 to 2011, 298 patients with atlantoaxial dislocation and atlas occipitalization were studied. Angles formed between Occiput-C2 and C2-C7 were measured. The relationship between the alignment of the occipital-cervical junction and the subaxial cervical spine was evaluated. The range of values for the angles measured was as followed: the Occiput-C2 angles were -35.2A degrees to 44.8A degrees, and the C2-C7 angles were -17.4A degrees to 77.8A degrees. Statistically significant negative correlations were observed between the Occiput-C2 and C2-C7 angles. Anterior dislocations of the atlas are associated with diminished lordosis or even kyphosis of the occipital-cervical junction, and result in compensatory hyperlordosis of the subaxial cervical spine, collectively presenting as a "swan neck" deformity. Atlantoaxial dislocation may influence the global cervical alignment. C1 [Wang, Shenglin; Yan, Ming; Zhou, Haitao; Wang, Chao] Peking Univ, Hosp 3, Dept Orthopaed, Beijing 100191, Peoples R China. [Passias, Peter G.; Li, Gang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA USA. [Cui, Libin] LUHE Hosp, Spine Dept, Beijing, Peoples R China. RP Wang, C (reprint author), Peking Univ, Hosp 3, Dept Orthopaed, 49 North Garden St, Beijing 100191, Peoples R China. EM wangchaoo@ynet.com NR 11 TC 2 Z9 3 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD JUL PY 2013 VL 22 IS 7 BP 1603 EP 1607 DI 10.1007/s00586-013-2742-4 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 175OS UT WOS:000321240600023 PM 23608933 ER PT J AU Clark, J Singer, S Kane, N Valentine, M AF Clark, Jonathan Singer, Sara Kane, Nancy Valentine, Melissa TI From striving to thriving: Systems thinking, strategy, and the performance of safety net hospitals SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE financial performance; safety net hospitals; strategy; systems thinking ID HEALTH-CARE; DYNAMIC CAPABILITIES; MARKET; DIVERSIFICATION; OUTCOMES; PROFIT AB Background: Safety net hospitals (SNH) have, on average, experienced declining financial margins and faced an elevated risk of closure over the past decade. Despite these challenges, not all SNHs are weakening and some are prospering. These higher-performing SNHs provide substantial care to safety net populations and produce sustainable financial returns. Purpose: Drawing on the alternative structural positioning and resource-based views, we explore strategic management as a source of performance differences across SNHs. Methodology/Approach: We employ a mixed-method design, blending quantitative and qualitative data and analysis. We measure financial performance using hospital operating margin and quantitatively evaluate its relationship with a limited set of well-defined structural positions. We further evaluate these structures and also explore the internal resources of SNHs based on nine in-depth case studies developed from site visits and extensive interviews. Findings: Quantitative results suggest that structural positions alone are not related to performance. Comparative case studies suggest that higher-performing SNH differ in four respects: (1) coordinating patient flow across the care continuum, (2) engaging in partnerships with other providers, (3) managing scope of services, and (4) investing in human capital. On the basis of these findings, we propose a model of strategic action related to systems thinking the ability to see wholes and interrelationships rather than individual parts alone. Practice Implications: Our exploratory findings suggest the need to move beyond generic strategies alone and acknowledge the importance of underlying managerial capabilities. Specifically, our findings suggest that effective strategy is a function of both the internal resources (e.g., managers' systems-thinking capability) and structural positions (e.g., partnerships) of organizations. From this perspective, framing resources and positioning as distinct alternatives misses the nuances of how strategic advantage is actually achieved. C1 [Clark, Jonathan] Penn State Univ, University Pk, PA 16802 USA. [Singer, Sara; Kane, Nancy] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Singer, Sara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Valentine, Melissa] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Valentine, Melissa] Grad Sch Arts & Sci, Boston, MA USA. RP Clark, J (reprint author), Penn State Univ, University Pk, PA 16802 USA. EM jrc24@psu.edu; ssinger@hsph.harvard.edu; nkane@hsph.harvard.edu; mvalentine@hbs.edu RI Clark, Jonathan/J-6172-2015 OI Clark, Jonathan/0000-0003-1860-4323 NR 42 TC 2 Z9 2 U1 5 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JUL-SEP PY 2013 VL 38 IS 3 BP 211 EP 223 DI 10.1097/HMR.0b013e31825ba9ab PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA 168IF UT WOS:000320698400004 PM 22647851 ER PT J AU Hyndman, KA Boesen, EI Elmarakby, AA Brands, MW Huang, P Kohan, DE Pollock, DM Pollock, JS AF Hyndman, Kelly A. Boesen, Erika I. Elmarakby, Ahmed A. Brands, Michael W. Huang, Paul Kohan, Donald E. Pollock, David M. Pollock, Jennifer S. TI Renal Collecting Duct NOS1 Maintains Fluid-Electrolyte Homeostasis and Blood Pressure SO HYPERTENSION LA English DT Article DE blood pressure; collecting duct; NOS1; salt-sensitivity; sodium excretion ID NITRIC-OXIDE SYNTHASE; CAUSES HYPERTENSION; SODIUM RETENTION; PULSE PRESSURE; SPLICE VARIANTS; CRE RECOMBINASE; RAT-KIDNEY; 1ST EXONS; ENDOTHELIN; KNOCKOUT AB Nitric oxide is a pronatriuretic and prodiuretic factor. The highest renal NO synthase (NOS) activity is found in the inner medullary collecting duct. The collecting duct (CD) is the site of daily fine-tune regulation of sodium balance, and led us to hypothesize that a CD-specific deletion of NOS1 would result in an impaired ability to excrete a sodium load leading to a salt-sensitive blood pressure phenotype. We bred AQP2-CRE mice with NOS1 floxed mice to produce flox control and CD-specific NOS1 knockout (CDNOS1KO) littermates. CDs from CDNOS1KO mice produced 75% less nitrite, and urinary nitrite+nitrate (NOx) excretion was significantly blunted in the knockout genotype. When challenged with high dietary sodium, CDNOS1KO mice showed significantly reduced urine output, sodium, chloride, and NOx excretion, and increased mean arterial pressure relative to flox control mice. In humans, urinary NOx is a newly identified biomarker for the progression of hypertension. These findings reveal that NOS1 in the CD is critical in the regulation of fluid-electrolyte balance, and this new genetic model of CD NOS1 gene deletion will be a valuable tool to study salt-dependent blood pressure mechanisms. C1 [Hyndman, Kelly A.; Boesen, Erika I.; Elmarakby, Ahmed A.; Pollock, David M.; Pollock, Jennifer S.] Georgia Regents Univ, Dept Med, Sect Expt Med, Augusta, GA 30912 USA. [Boesen, Erika I.; Brands, Michael W.; Pollock, David M.; Pollock, Jennifer S.] Georgia Regents Univ, Dept Physiol, Augusta, GA 30912 USA. [Elmarakby, Ahmed A.] Georgia Regents Univ, Dept Oral Biol, Augusta, GA 30912 USA. [Huang, Paul] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. [Huang, Paul] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Kohan, Donald E.] Univ Utah, Hlth Sci Ctr, Div Nephrol, Salt Lake City, UT USA. RP Pollock, JS (reprint author), Georgia Regents Univ, Dept Med, Sect Expt Med, CB2209,1459 Laney Walker Blvd, Augusta, GA 30912 USA. EM jpollock@gru.edu OI Hyndman, Kelly/0000-0002-8465-2588 FU National Institutes of Health [HL60653]; Cardiovascular Discovery Institute; National Kidney Foundation Post Doctoral Fellowship; NIH [HL95499] FX This work was supported in part by the National Institutes of Health (HL60653 to J.S. Pollock); Cardiovascular Discovery Institute (to D. M. Pollock); and the National Kidney Foundation Post Doctoral Fellowship (to K. A. Hyndman). This work was also supported by the NIH Program Project Grant on Endothelin Control of Renal Excretory and Hemodynamic Function (HL95499; to D. M. Pollock, J.S. Pollock, and D. E. Kohan). NR 57 TC 28 Z9 28 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2013 VL 62 IS 1 BP 91 EP 98 DI 10.1161/HYPERTENSIONAHA.113.01291 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 162YR UT WOS:000320302600019 PM 23608660 ER PT J AU Rychert, J Burnham, CAD Bythrow, M Garner, OB Ginocchio, CC Jennemann, R Lewinski, MA Manji, R Mochon, AB Procop, GW Richter, SS Sercia, L Westblade, LF Ferraro, MJ Branda, JA AF Rychert, Jenna Burnham, Carey-Ann D. Bythrow, Maureen Garner, Omai B. Ginocchio, Christine C. Jennemann, Rebecca Lewinski, Michael A. Manji, Ryhana Mochon, A. Brian Procop, Gary W. Richter, Sandra S. Sercia, Linda Westblade, Lars F. Ferraro, Mary Jane Branda, John A. TI Multicenter Evaluation of the Vitek MS Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry System for Identification of Gram-Positive Aerobic Bacteria SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; ALPHA-HEMOLYTIC STREPTOCOCCI; SPECIES IDENTIFICATION; ROUTINE IDENTIFICATION; CLINICAL MICROBIOLOGY; DESORPTION/IONIZATION-TIME; RAPID IDENTIFICATION; ANAEROBIC-BACTERIA; COST-EFFECTIVENESS; BIOTYPER AB Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) is gaining momentum as a tool for bacterial identification in the clinical microbiology laboratory. Compared with conventional methods, this technology can more readily and conveniently identify a wide range of organisms. Here, we report the findings from a multicenter study to evaluate the Vitek MS v2.0 system (bioMerieux, Inc.) for the identification of aerobic Gram-positive bacteria. A total of 1,146 unique isolates, representing 13 genera and 42 species, were analyzed, and results were compared to those obtained by nucleic acid sequence-based identification as the reference method. For 1,063 of 1,146 isolates (92.8%), the Vitek MS provided a single identification that was accurate to the species level. For an additional 31 isolates (2.7%), multiple possible identifications were provided, all correct at the genus level. Mixed-genus or single-choice incorrect identifications were provided for 18 isolates (1.6%). Although no identification was obtained for 33 isolates (2.9%), there was no specific bacterial species for which the Vitek MS consistently failed to provide identification. In a subset of 463 isolates representing commonly encountered important pathogens, 95% were accurately identified to the species level and there were no misidentifications. Also, in all but one instance, the Vitek MS correctly differentiated Streptococcus pneumoniae from other viridans group streptococci. The findings demonstrate that the Vitek MS system is highly accurate for the identification of Gram-positive aerobic bacteria in the clinical laboratory setting. C1 [Rychert, Jenna; Ferraro, Mary Jane; Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rychert, Jenna; Ferraro, Mary Jane; Branda, John A.] Harvard Univ, Sch Med, Boston, MA USA. [Burnham, Carey-Ann D.; Westblade, Lars F.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Jennemann, Rebecca] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Bythrow, Maureen; Manji, Ryhana] North Shore LIJ Hlth Syst Labs, Dept Pathol & Lab Med, Lake Success, NY USA. [Garner, Omai B.; Lewinski, Michael A.; Mochon, A. Brian] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Ginocchio, Christine C.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. [Procop, Gary W.; Richter, Sandra S.; Sercia, Linda] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. RP Rychert, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jrychert@partners.org OI Burnham, Carey-Ann/0000-0002-1137-840X FU bioMerieux, Inc., Durham, NC; bioMerieux; Becton, Dickinson; Accler8; Cepheid; T2 Biosystems; Bruker; CDC; Luminex; Nanosphere; Forest Laboratories FX This study was performed as part of an FDA trial of the Vitek MS v2.0 system and was funded by the device manufacturer (bioMerieux, Inc., Durham, NC). M.J.F., J.A.B., and J.R. have received research funding from bioMerieux and Becton, Dickinson. C.-A.D.B has received research funding from bioMerieux, Accler8, Cepheid, and T2 Biosystems. C.C.G. has received research funding and consultant fees from bioMerieux and Becton Dickenson. G.W.P. has received research funding from bioMerieux, Bruker, CDC, and Luminex. S.S.R. has received research funding from bioMerieux, Nanosphere, and Forest Laboratories. NR 43 TC 44 Z9 45 U1 0 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2013 VL 51 IS 7 BP 2225 EP 2231 DI 10.1128/JCM.00682-13 PG 7 WC Microbiology SC Microbiology GA 166YB UT WOS:000320595800030 PM 23658261 ER PT J AU Westblade, LF Jennemann, R Branda, JA Bythrow, M Ferraro, MJ Garner, OB Ginocchio, CC Lewinski, MA Manji, R Mochon, AB Procop, GW Richter, SS Rychert, JA Sercia, L Burnhama, CAD AF Westblade, Lars F. Jennemann, Rebecca Branda, John A. Bythrow, Maureen Ferraro, Mary Jane Garner, Omai B. Ginocchio, Christine C. Lewinski, Michael A. Manji, Ryhana Mochon, A. Brian Procop, Gary W. Richter, Sandra S. Rychert, Jenna A. Sercia, Linda Burnhama, Carey-Ann D. TI Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID DESORPTION IONIZATION-TIME; FLIGHT MASS-SPECTROMETRY; INVASIVE FUNGAL-INFECTIONS; CRYPTOCOCCUS-GATTII; CANDIDIASIS; CANDIDEMIA; EXPERIENCE; MANAGEMENT; STRATEGY; THERAPY AB The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMerieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20 Candida species (626 isolates, including 58 C. albicans, 62 C. glabrata, and 53 C. krusei isolates), 35 Cryptococcus neoformans isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of C. albicans (n = 58) identified as Candida dubliniensis, one isolate of Candida parapsilosis (n = 73) identified as Candida pelliculosa, and three isolates of Geotrichum klebahnii (n = 6) identified as Geotrichum candidum. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories. C1 [Westblade, Lars F.; Burnhama, Carey-Ann D.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Westblade, Lars F.; Ginocchio, Christine C.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. [Jennemann, Rebecca] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Branda, John A.; Ferraro, Mary Jane; Rychert, Jenna A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, John A.; Ferraro, Mary Jane; Rychert, Jenna A.] Harvard Univ, Sch Med, Boston, MA USA. [Bythrow, Maureen; Ginocchio, Christine C.; Manji, Ryhana] North Shore LIJ Hlth Syst Labs, Dept Pathol & Lab Med, Lake Success, NY USA. [Lewinski, Michael A.; Mochon, A. Brian] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Procop, Gary W.; Richter, Sandra S.; Sercia, Linda] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. RP Burnhama, CAD (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. EM cburnham@path.wustl.edu OI Burnham, Carey-Ann/0000-0002-1137-840X FU bioMerieux; Becton, Dickinson and Co.; Becton, Dickinson; Bruker; CDC; Luminex; Nanosphere; Forest Laboratories; Acclerate; Cepheid; T2 Biosystems FX This study was funded by bioMerieux.; J. A. Branda, J. A. Rychert, and M. J. Ferraro have received research funding from bioMerieux and Becton, Dickinson and Co. C. C. Ginocchio has received research funding and consulting fees from bioMerieux and Becton, Dickinson. G. W. Procop has received research funding from bioMerieux, Bruker, the CDC, and Luminex. S. S. Richter has received research funding from bioMerieux, Nanosphere, and Forest Laboratories. C.-A. D. Burnham has received research funding from bioMerieux, Acclerate, Cepheid, and T2 Biosystems. The other authors have no conflicts to disclose. NR 36 TC 40 Z9 41 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2013 VL 51 IS 7 BP 2267 EP 2272 DI 10.1128/JCM.00680-13 PG 6 WC Microbiology SC Microbiology GA 166YB UT WOS:000320595800036 PM 23658267 ER PT J AU Penzes, P Buonanno, A Passafaro, M Sala, C Sweet, RA AF Penzes, Peter Buonanno, Andres Passafaro, Maria Sala, Carlo Sweet, Robert A. TI Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE Alzheimer's disease; autism; dendritic spine; dopamine; ErbB4; GABAergic interneuron ID LINKED MENTAL-RETARDATION; AUTISM SPECTRUM DISORDER; CENTRAL-NERVOUS-SYSTEM; PARVALBUMIN-POSITIVE INTERNEURONS; HIPPOCAMPAL GAMMA OSCILLATIONS; DENDRITIC SPINE MORPHOGENESIS; GLUTAMIC-ACID DECARBOXYLASE; 22Q13.3 DELETION SYNDROME; INCREASED FAMILIAL RISK; EARLY-ONSET PSYCHOSIS AB Psychiatric and neurodegenerative disorders, including intellectual disability, autism spectrum disorders (ASD), schizophrenia (SZ), and Alzheimer's disease, pose an immense burden to society. Symptoms of these disorders become manifest at different stages of life: early childhood, adolescence, and late adulthood, respectively. Progress has been made in recent years toward understanding the genetic substrates, cellular mechanisms, brain circuits, and endophenotypes of these disorders. Multiple lines of evidence implicate excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis in these disorders. Excitatory/inhibitory balance - modulated largely by dopamine - critically regulates cortical network function, neural network activity (i.e. gamma oscillations) and behaviors associated with psychiatric disorders. Understanding the molecular underpinnings of synaptic pathology and neuronal network activity may thus provide essential insight into the pathogenesis of these disorders and can reveal novel drug targets to treat them. Here, we discuss recent genetic, neuropathological, and molecular studies that implicate alterations in excitatory and inhibitory synaptic circuits in the pathogenesis of psychiatric disorders across the lifespan. C1 [Penzes, Peter] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Penzes, Peter] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Buonanno, Andres] Eunice Shriver Kennedy NICHD, Mol Neurobiol Sect, NIH, Program Dev Neurobiol, Bethesda, MD USA. [Passafaro, Maria; Sala, Carlo] Univ Milan, CNR Inst Neurosci, Milan, Italy. [Passafaro, Maria; Sala, Carlo] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy. [Passafaro, Maria] CNR, Inst Neurosci, Dulbecco Telethon Inst, I-20133 Milan, Italy. [Sala, Carlo] Neurol Inst, Milan, Italy. [Sala, Carlo] Fdn Carlo Besta, Milan, Italy. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Penzes, P (reprint author), Northwestern Univ, Dept Physiol, Feinberg Sch Med, 303 E,Chicago Ave, Chicago, IL 60611 USA. EM p-penzes@northwestern.edu RI Penzes, Peter/L-3987-2016; Sala, Carlo/A-2493-2009 OI Penzes, Peter/0000-0001-5449-1640; Sala, Carlo/0000-0003-0662-9523 FU NIH [MH071316, MH097216, MH071533, AG027224]; Eunice Shriver Kennedy National Institute of Child Health and Human Development Intramural Research Program; Veterans Health Administration [BX000452]; Comitato Telethon Fondazione Onlus [GGP09196, GGP11095, GGP12097, GGP11116B]; Fondazione CARI-PLO project [2009.264]; Italian Institute of Technology, Seed Grant, Ministry of Health in the frame of ERA-NET NEURON and PNR-CNR Aging Program FX This study was supported by NIH grants MH071316 and MH097216 to P. P., Eunice Shriver Kennedy National Institute of Child Health and Human Development Intramural Research Program to A. B., Veterans Health Administration Grant BX000452 and NIH Grants MH071533 and AG027224 to R. A. S. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States government. We thank Ruoqi Gao for assistance with editing the manuscript. This study was financially supported by Comitato Telethon Fondazione Onlus, grant n. GGP09196 and GGP11095 (to CS), n. GGP12097 and GGP11116B (to MP) Fondazione CARI-PLO project number 2009.264, Italian Institute of Technology, Seed Grant, Ministry of Health in the frame of ERA-NET NEURON and PNR-CNR Aging Program 2012-2014 (to CS). The authors declare no conflicts of interest. NR 217 TC 40 Z9 41 U1 5 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2013 VL 126 IS 2 BP 165 EP 182 DI 10.1111/jnc.12261 PG 18 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 175DY UT WOS:000321211700004 PM 23574039 ER PT J AU Eskandar, E AF Eskandar, Emad TI Functional mapping SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, E (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2013 VL 119 IS 1 BP 24 EP 24 DI 10.3171/2012.11.JNS121318 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168WT UT WOS:000320739300008 PM 23600940 ER PT J AU Hong, B Qian, TY Liu, HS Zhou, WJ AF Hong, Bo Qian, Tianyi Liu, Hesheng Zhou, Wenjing TI Functional mapping Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID CORTICAL STIMULATION; GAMMA BAND; LANGUAGE C1 [Hong, Bo; Qian, Tianyi] Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China. [Zhou, Wenjing] Tsinghua Univ, Yuquan Hosp, Dept Neurosurg, Beijing 100084, Peoples R China. [Zhou, Wenjing] Tsinghua Univ, Yuquan Hosp, Epilepsy Ctr, Beijing 100084, Peoples R China. [Qian, Tianyi; Liu, Hesheng] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Hong, B (reprint author), Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China. NR 9 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2013 VL 119 IS 1 BP 24 EP 25 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168WT UT WOS:000320739300009 PM 23977689 ER PT J AU Qian, TY Zhou, WJ Ling, ZP Gao, SK Liu, HS Hong, B AF Qian, Tianyi Zhou, Wenjing Ling, Zhipei Gao, Shangkai Liu, Hesheng Hong, Bo TI Fast presurgical functional mapping using task-related intracranial high gamma activity Laboratory investigation SO JOURNAL OF NEUROSURGERY LA English DT Article DE epilepsy surgery; functional mapping; high gamma activity; motor cortex ID HUMAN SENSORIMOTOR CORTEX; ELECTROCORTICOGRAPHIC SPECTRAL-ANALYSIS; MOTOR CORTEX; CORTICAL STIMULATION; BAND ACTIVITY; ELECTRICAL-STIMULATION; BRAIN-TUMORS; LANGUAGE; TIME; SYNCHRONIZATION AB Object. Electrocorticography (ECoG) is a powerful tool for presurgical functional mapping. Power increase in the high gamma band has been observed from ECoG electrodes on the surface of the sensory motor cortex during the execution of body movements. In this study the authors aim to validate the clinical usage of high gamma activity in presurgical mapping by comparing ECoG mapping with traditional direct electrical cortical stimulation (ECS) and functional MRI (fMRI) mapping. Methods. Seventeen patients with epilepsy participated in an ECoG motor mapping experiment. The patients executed a 5-minute hand/tongue movement task while the ECoG signal was recorded. All 17 patients also underwent extraoperative ECS mapping to localize the motor cortex. Eight patients also participated in a presurgical fMRI study. The high gamma activity on ECoG was modeled using the general linear model (GLM), and the regions showing significant gamma power increase during the task condition compared with the rest condition were localized. The maps derived from GLM-based ECoG mapping, ECS, and fMRI were then compared. Results. High gamma activity in the motor cortex can be reliably modulated by motor tasks. Localization of the motor regions achieved with GLM-based ECoG mapping was consistent with the localization determined by ECS. The maps also appeared to be highly localized compared with the fMRI activations. Using the ECS findings as the reference, GLM-based ECoG mapping showed a significantly higher sensitivity than fMRI (66.7% for ECoG, 52.6% for fMRI, p < 0.05), while the specificity was high for both techniques (> 97%). If the current-spreading effect in ECS is accounted for, ECoG mapping may produce maps almost identical to those produced by ECS mapping (100% sensitivity and 99.5% specificity). Conclusions. General linear model based ECoG mapping showed a superior performance compared to traditional ECS and fMRI mapping in terms of efficiency and accuracy. Using this method, motor functions can be reliably mapped in less than 5 minutes. C1 [Qian, Tianyi; Gao, Shangkai; Hong, Bo] Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China. [Zhou, Wenjing] Tsinghua Univ, Yuquan Hosp, Dept Neurosurg, Beijing 100084, Peoples R China. [Zhou, Wenjing] Tsinghua Univ, Yuquan Hosp, Epilepsy Ctr, Beijing 100084, Peoples R China. [Ling, Zhipei] Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, Beijing, Peoples R China. [Qian, Tianyi; Liu, Hesheng] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Hong, B (reprint author), Tsinghua Univ, Sch Med, Dept Biomed Engn, Med Sch Bldg B204,Qinghua Yuan 1, Beijing 100084, Peoples R China. EM hongbo@tsinghua.edu.cn OI Liu, Hesheng/0000-0002-7233-1509 FU National Science Foundation of China [61071003]; National Basic Research Program of China [2011CB933204]; NIH [K25NS069805]; China Scholarship Council FX The work was supported by National Science Foundation of China 61071003 (B. Hong), National Basic Research Program of China 2011CB933204 (B. Hong), and NIH grant K25NS069805 (H. Liu). Tianyi Qian was partly supported by the Postgraduate Study Abroad Program of China Scholarship Council. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. NR 61 TC 9 Z9 11 U1 0 U2 10 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2013 VL 119 IS 1 BP 26 EP 36 DI 10.3171/2013.2.JNS12843 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168WT UT WOS:000320739300010 PM 23600935 ER PT J AU Eskandar, E AF Eskandar, Emad TI Deep brain stimulation and obesity SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, E (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2013 VL 119 IS 1 BP 54 EP 54 DI 10.3171/2012.11.JNS121486 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168WT UT WOS:000320739300013 PM 23560575 ER PT J AU Johnson, KA Minoshima, S Bohnen, NI Donohoe, KJ Foster, NL Herscovitch, P Karlawish, JH Rowe, CC Hedrick, S Pappas, V Carrillo, MC Hartley, DM AF Johnson, Keith A. Minoshima, Satoshi Bohnen, Nicolaas I. Donohoe, Kevin J. Foster, Norman L. Herscovitch, Peter Karlawish, Jason H. Rowe, Christopher C. Hedrick, Saima Pappas, Virginia Carrillo, Maria C. Hartley, Dean M. TI Update on Appropriate Use Criteria for Amyloid PET Imaging: Dementia Experts, Mild Cognitive Impairment, and Education SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE amyloid PET; dementia; Alzheimer disease ID ALZHEIMERS ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOMMENDATIONS; DISEASE AB Amyloid PET imaging is a novel diagnostic test that can detect in living humans one of the two defining pathologic lesions of Alzheimer disease, amyloid-beta deposition in the brain. The Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging previously published appropriate use criteria for amyloid PET as an important tool for increasing the certainty of a diagnosis of Alzheimer disease in specific patient populations. Here, the task force further clarifies and expands 3 topics discussed in the original paper: first, defining dementia experts and their use of proper documentation to demonstrate the medical necessity of an amyloid PET scan; second, identifying a specific subset of individuals with mild cognitive impairment for whom an amyloid PET scan is appropriate; and finally, developing educational programs to increase awareness of the amyloid PET appropriate use criteria and providing instructions on how this test should be used in the clinical decision-making process. C1 [Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Bohnen, Nicolaas I.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Bohnen, Nicolaas I.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Bohnen, Nicolaas I.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Donohoe, Kevin J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Foster, Norman L.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. [Karlawish, Jason H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia. [Rowe, Christopher C.] Austin Hlth, Ctr PET, Melbourne, Vic, Australia. [Hedrick, Saima; Pappas, Virginia] Soc Nucl Med & Mol Imaging, Reston, VA USA. [Carrillo, Maria C.; Hartley, Dean M.] Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL 60601 USA. RP Carrillo, MC (reprint author), Alzheimers Assoc, Div Med & Sci Relat, 225 N Michigan Ave, Chicago, IL 60601 USA. EM maria.carrillo@alz.org FU NIA NIH HHS [P30 AG010124] NR 4 TC 19 Z9 19 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL 1 PY 2013 VL 54 IS 7 BP 1011 EP 1013 DI 10.2967/jnumed.113.127068 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173WR UT WOS:000321113500005 PM 23753186 ER PT J AU Liu, X Hirano, AA Sun, XP Brecha, NC Barnes, S AF Liu, Xue Hirano, Arlene A. Sun, Xiaoping Brecha, Nicholas C. Barnes, Steven TI Calcium channels in rat horizontal cells regulate feedback inhibition of photoreceptors through an unconventional GABA- and pH-sensitive mechanism SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID TIGER SALAMANDER RETINA; OUTER PLEXIFORM LAYER; CONE PHOTORECEPTORS; ROD PHOTORECEPTORS; MOUSE RETINA; INTRACELLULAR CALCIUM; TRANSMITTER RELEASE; VERTEBRATE RETINA; PLASMA-MEMBRANE; GOLDFISH RETINA AB Horizontal cells send inhibitory feedback to photoreceptors, helping form antagonistic receptive fields in the retina, but the neurotransmitter and the mechanisms underlying this signalling are not known. Since the proteins responsible for conventional Ca2+-dependent release of GABAergic synaptic vesicles are present in mammalian horizontal cells, we investigated this conventional mechanism as the means by which horizontal cells inhibit photoreceptors. Using Ca2+ imaging in rat retinal slices, we confirm that horizontal cell depolarization with kainate inhibits and horizontal cell hyperpolarization with NBQX disinhibits the Ca2+ signals produced by pH-sensitive activation of voltage-gated calcium channels (Ca channels) in photoreceptors. We show that while 100 mu M Co2+ reduces photoreceptor Ca2+ signals, it disinhibits them at 10 mu M, an effect reminiscent of earlier studies where low [Co2+] eliminated feedback. The low [Co2+] disinhibition is pH sensitive. We localized L-, N- and P/Q-type Ca channels in rat horizontal cells, and showed that both the N-type Ca channel blocker omega-conotoxin GVIA and the P/Q-type Ca channel blocker omega-agatoxin IVA increased Ca2+ signals in photoreceptors in a pH-sensitive manner. Pronounced actions of GABAergic agents on feedback signals to photoreceptors were observed, and are pH sensitive, but are inconsistent with direct inhibition by GABA of photoreceptor [Ca2+]. Patch-clamp studies revealed that GABA activates a conductance having high bicarbonate permeability in isolated horizontal cells, suggesting that the commonality of pH sensitivity throughout the results could arise from a GABA autofeedback action in horizontal cells. This could change cleft pH with concomitant inhibitory influences on photoreceptor Ca channels. C1 [Liu, Xue; Hirano, Arlene A.; Sun, Xiaoping; Brecha, Nicholas C.; Barnes, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Liu, Xue; Hirano, Arlene A.; Sun, Xiaoping; Brecha, Nicholas C.; Barnes, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Hirano, Arlene A.; Brecha, Nicholas C.; Barnes, Steven] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Barnes, Steven] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS, Canada. [Barnes, Steven] Dalhousie Univ, Dept Ophthalmol & Visual Sci, Halifax, NS, Canada. RP Barnes, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. EM sbarnes@dal.ca FU National Eye Institute [EY15573]; UCLA Oppenheimer Seed Grant; Plum Foundation; Canadian Institutes of Health Research [MOP-10968]; National Science and Engineering Research Council; Veterans Administration Senior Career Scientist Award FX Support for this work was provided by grants from the National Eye Institute (EY15573 to N.C.B.), a UCLA Oppenheimer Seed Grant (A. A. H.), the Plum Foundation (S. B. and N.C.B.), the Canadian Institutes of Health Research (MOP-10968 to S. B.), the National Science and Engineering Research Council (Discovery Award to S. B.), and a Veterans Administration Senior Career Scientist Award (N.C.B.). NR 70 TC 20 Z9 20 U1 0 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 1 PY 2013 VL 591 IS 13 BP 3309 EP 3324 DI 10.1113/jphysiol.2012.248179 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 174XV UT WOS:000321192000019 PM 23613534 ER PT J AU Black, EM Higgins, LD Warner, JJP AF Black, Eric M. Higgins, Laurence D. Warner, Jon J. P. TI Value-based shoulder surgery: practicing outcomes-driven, cost-conscious care SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Review DE Value-based surgery; value; shoulder surgery; outcomes; cost ID ROTATOR CUFF REPAIR; TOTAL JOINT REPLACEMENT; LENGTH-OF-STAY; HEALTH-CARE; ADHESIVE CAPSULITIS; ECONOMIC-EVALUATION; ORTHOPEDIC-SURGERY; PROVIDER VOLUME; DATA-COLLECTION; ARTHROPLASTY AB Background: Pathology of the shoulder contributes significantly to the increasing burden of musculoskeletal disease. Currently, there exists high variability in the nature and quality of shoulder care, and outcomes and cost reporting are not uniform. Value-based practice aims to simultaneously maximize outcomes and minimize costs for given disease processes. Methods: The current state of the shoulder care literature was examined with regards to cost and outcomes data, initiatives in streamlining care delivery, and evidence-based practice improvements. This was synthesized with value-based care theory to propose new avenues to improve shoulder care in the future. Conclusion: The treatment of shoulder disorders is ideal for the value-based model but has been slow to adopt its principles thus far. We can begin to advance value-based practices through (1) the universal reporting of outcomes and costs, (2) integrating shoulder care across provider specialties, and (3) critically analyzing data to formulate best practices. Level of evidence: Narrative Review. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Black, Eric M.; Higgins, Laurence D.; Warner, Jon J. P.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02115 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Ste 3200,3G,Rm 3-046,55 Fruit St, Boston, MA 02114 USA. EM jwarner@partners.org NR 69 TC 7 Z9 7 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUL PY 2013 VL 22 IS 7 BP 1000 EP 1009 DI 10.1016/j.jse.2013.02.008 PG 10 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 172IR UT WOS:000320996100027 PM 23659804 ER PT J AU DeSimone, JA Guenova, E Carter, JB Chaney, KS Aldridge, JR Noell, CM Dorosario, AA Hansen, JL Kupper, TS Devlin, PM AF DeSimone, Jennifer A. Guenova, Emmanuella Carter, Joi B. Chaney, Keri S. Aldridge, Julie R. Noell, Claire M. Dorosario, Andrew A. Hansen, Jorgen L. Kupper, Thomas S. Devlin, Phillip M. TI Low-dose high-dose-rate brachytherapy in the treatment of facial lesions of cutaneous T-cell lymphoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE convex surface; cutaneous T-cell lymphoma; facial lesions; mycosis fungoides; photon brachytherapy; radiation; skin-directed therapy ID MYCOSIS-FUNGOIDES; CANCER AB Background: The use of many of the standard skin-directed mycosis fungoides (MF) therapies on facial skin may be limited by site-specific increased risks of side effects, excessive inflammation, and ocular toxicity. Objective: Our study aimed to describe the levels of erythema, scale, and induration of facial lesions in MF before and after low-dose high-dose-rate surface applicator brachytherapy and to examine the overall clinical response to brachytherapy. Methods: A total of 23 facial MF lesions in 10 patients were treated with high-dose-rate brachytherapy doses of 4 Gy per session for a total of 2 fractions at our multidisciplinary cutaneous oncology clinic between August 17, 2009, and March 12, 2012. Results: In all 23 lesions, dramatic clinical improvement was observed. Patients were followed up for a median of 6.3 months. No recurrences were reported in the follow-up period. Limitations: Long-term follow-up is lacking. Reassessment of all included patients at annual intervals for a period of at least 5 years is the authors' goal. Conclusion: Low-dose high-dose-rate brachytherapy using custom-made surface molds is a highly efficacious therapy in the treatment of facial lesions in MF. C1 [DeSimone, Jennifer A.; Guenova, Emmanuella; Carter, Joi B.; Chaney, Keri S.; Dorosario, Andrew A.; Kupper, Thomas S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. [Aldridge, Julie R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Noell, Claire M.; Hansen, Jorgen L.; Devlin, Phillip M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Guenova, E (reprint author), Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, EBRC Room 505,221 Longwood Ave, Boston, MA 02115 USA. EM emmanuella.guenova@gmail.com RI Guenova, Emmanuella/A-4656-2015 FU German Research Foundation [GU1271/2-1] FX Supported by a grant from the German Research Foundation (No. GU1271/2-1 to Dr Guenova). NR 10 TC 7 Z9 7 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2013 VL 69 IS 1 BP 61 EP 65 DI 10.1016/j.jaad.2012.12.975 PG 5 WC Dermatology SC Dermatology GA 165UG UT WOS:000320510100023 PM 23453243 ER PT J AU Chen, YE Tsao, H AF Chen, Yiyin Erin Tsao, Hensin TI The skin microbiome: Current perspectives and future challenges SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE antibiotics; atopic dermatitis; Human Microbiome Project; immunology; innate immunity; metagenomics; skin cancer; skin microbiome ID RESISTANT STAPHYLOCOCCUS-AUREUS; PLACEBO-CONTROLLED TRIAL; ATOPIC-DERMATITIS; ANTIMICROBIAL PEPTIDES; MOLECULAR ANALYSIS; HELICOBACTER-PYLORI; BACTERIAL BIOTA; PROPIONIBACTERIUM-ACNES; VIRULENCE DETERMINANTS; ANTIBIOTIC-RESISTANCE AB Complex communities of bacteria, fungi, and viruses thrive on our skin. The composition of these communities depends on skin characteristics, such as sebaceous gland concentration, moisture content, and temperature, as well as on host genetics and exogenous environmental factors. Recent metagenomic studies have uncovered a surprising diversity within these ecosystems and have fostered a new view of commensal organisms as playing a much larger role in immune modulation and epithelial health than previously expected. Understanding microbe-host interactions and discovering the factors that drive microbial colonization will help us understand the pathogenesis of skin diseases and develop new promicrobial and antimicrobial therapeutics. C1 [Chen, Yiyin Erin] Harvard Univ, Sch Med, Med Scientist Training Program, Boston, MA USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Wellman Ctr Photomed, Boston, MA USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Edwards 211, Boston, MA 02114 USA. EM htsao@partners.org FU NCI NIH HHS [K24 CA149202] NR 142 TC 35 Z9 40 U1 7 U2 97 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2013 VL 69 IS 1 BP 143 EP + DI 10.1016/j.jaad.2013.01.016 PG 16 WC Dermatology SC Dermatology GA 165UG UT WOS:000320510100034 PM 23489584 ER PT J AU Stratman, E Kirsner, RS Horn, TD AF Stratman, Erik Kirsner, Robert S. Horn, Thomas D. TI Maintenance of Certification in dermatology: What we know, what we don't SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE American Board of Dermatology; American Board of Medical Specialties; dermatology; Maintenance of Certification; Maintenance of Licensure ID CONTINUING MEDICAL-EDUCATION; QUALITY-OF-CARE; BOARD CERTIFICATION; AMERICAN-BOARD; PHYSICIAN PERFORMANCE; HEALTH-CARE; RECERTIFICATION; COMPETENCE; EXPERIENCE; PROGRAM AB Participation in Maintenance of Certification is a reality for the majority of board-certified physicians in the United States. It consists of 4 parts that focus the attention of participants on knowledge assessment, practice performance, communication skills, and patient safety. This continuing medical education article reviews the development and possible future of the program, data regarding Maintenance of Certification, what is currently not known about Maintenance of Certification, and how to navigate the requirements for dermatologists. C1 [Stratman, Erik] Marshfield Clin Fdn Med Res & Educ, Dept Dermatol, Marshfield, WI USA. [Kirsner, Robert S.] Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg, Coral Gables, FL 33124 USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA 02138 USA. RP Horn, TD (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR 622,55 Fruit St, Boston, MA 02114 USA. EM thorn@partners.org NR 42 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2013 VL 69 IS 1 AR 1.e1 DI 10.1016/j.jaad.2013.03.033 PG 11 WC Dermatology SC Dermatology GA 165UG UT WOS:000320510100015 PM 23768297 ER PT J AU Stratman, E Kirsner, RS Horn, TD AF Stratman, Erik Kirsner, Robert S. Horn, Thomas D. TI Maintenance of Certification in dermatology: Requirements for diplomates SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE American Board of Dermatology; American Board of Medical Specialties; dermatology; maintenance of certification; maintenance of licensure AB Since 2006, after completing a cognitive certifying or recertifying examination, dermatologists are automatically enrolled into Maintenance of Certification (MOC) and can access a personalized electronic table (at www.abderm.org) that presents the requirements over the 10-year cycle. On this web site, diplomates can also pay the annual fee and attest to completion of the various components. Clicking on hyperlinks in the table launches explanations of the requirements. A hyperlink below the table takes the reader to the various resources approved for completion of the MOC requirements. There is a login tab in the upper left corner with a login help feature below. Clicking on the MOC tab will bring up the table. The timeline is specific to the individual. C1 [Stratman, Erik] Marshfield Clin Fdn Med Res & Educ, Dept Dermatol, Marshfield, WI USA. [Kirsner, Robert S.] Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg, Coral Gables, FL 33124 USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. [Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA 02138 USA. RP Horn, TD (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR 622,55 Fruit St, Boston, MA 02114 USA. EM thorn@partners.org NR 1 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2013 VL 69 IS 1 AR 13.e1 DI 10.1016/j.jaad.2013.04.009 PG 4 WC Dermatology SC Dermatology GA 165UG UT WOS:000320510100016 PM 23768298 ER PT J AU Papillon-Cavanagh, S De Jay, N Hachem, N Olsen, C Bontempi, G Aerts, HJWL Quackenbush, J Haibe-Kains, B AF Papillon-Cavanagh, Simon De Jay, Nicolas Hachem, Nehme Olsen, Catharina Bontempi, Gianluca Aerts, Hugo J. W. L. Quackenbush, John Haibe-Kains, Benjamin TI Comparison and validation of genomic predictors for anticancer drug sensitivity SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CANCER-CELL-LINES; GENE-EXPRESSION; MICROARRAY DATA; MODELS; REGULARIZATION; IDENTIFICATION; SELECTION; SURVIVAL; MARKERS; RISK AB Background An enduring challenge in personalized medicine lies in selecting the right drug for each individual patient. While testing of drugs on patients in large trials is the only way to assess their clinical efficacy and toxicity, we dramatically lack resources to test the hundreds of drugs currently under development. Therefore the use of preclinical model systems has been intensively investigated as this approach enables response to hundreds of drugs to be tested in multiple cell lines in parallel. Methods Two large-scale pharmacogenomic studies recently screened multiple anticancer drugs on over 1000 cell lines. We propose to combine these datasets to build and robustly validate genomic predictors of drug response. We compared five different approaches for building predictors of increasing complexity. We assessed their performance in cross-validation and in two large validation sets, one containing the same cell lines present in the training set and another dataset composed of cell lines that have never been used during the training phase. Results Sixteen drugs were found in common between the datasets. We were able to validate multivariate predictors for three out of the 16 tested drugs, namely irinotecan, PD-0325901, and PLX4720. Moreover, we observed that response to 17-AAG, an inhibitor of Hsp90, could be efficiently predicted by the expression level of a single gene, NQO1. Conclusion These results suggest that genomic predictors could be robustly validated for specific drugs. If successfully validated in patients' tumor cells, and subsequently in clinical trials, they could act as companion tests for the corresponding drugs and play an important role in personalized medicine. C1 [Papillon-Cavanagh, Simon; De Jay, Nicolas; Hachem, Nehme; Haibe-Kains, Benjamin] Univ Montreal, Bioinformat & Computat Genom Lab, Inst Rech Clin Montreal, Montreal, PQ, Canada. [Olsen, Catharina; Bontempi, Gianluca] Univ Libre Brussels, Machine Learning Grp, Brussels, Belgium. [Aerts, Hugo J. W. L.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.; Quackenbush, John] Harvard Univ, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Haibe-Kains, B (reprint author), Inst Rech Clin Montreal, Bioinformat & Computat Genom Lab, 110 Ave Pins Ouest, Montreal, PQ H2W 1R7, Canada. EM bhaibeka@ircm.qc.ca RI Haibe-Kains, Benjamin/D-3702-2011; Aerts, Hugo/P-6350-2015 OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Aerts, Hugo/0000-0002-2122-2003 FU start-up fund of Benjamin Haibe-Kains; National Library of Medicine of the US National Institutes of Health [R01 LM010129-01]; Claudia Adams Barr Program in Innovative Basic Cancer Research; Belgian French Community ARC (Action de Recherche Concertee) FX SPC, NDJ and NH were supported by the start-up fund of Benjamin Haibe-Kains. JQ was supported by a grant from the National Library of Medicine of the US National Institutes of Health (R01 LM010129-01) and by a grant from the Claudia Adams Barr Program in Innovative Basic Cancer Research. GB and CO were supported by the Belgian French Community ARC (Action de Recherche Concertee) funding. NR 39 TC 19 Z9 19 U1 0 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2013 VL 20 IS 4 BP 597 EP 602 DI 10.1136/amiajnl-2012-001442 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 161CJ UT WOS:000320168600002 PM 23355484 ER PT J AU Singh, H Spitzmueller, C Petersen, NJ Sawhney, MK Smith, MW Murphy, DR Espadas, D Laxmisan, A Sittig, DF AF Singh, Hardeep Spitzmueller, Christiane Petersen, Nancy J. Sawhney, Mona K. Smith, Michael W. Murphy, Daniel R. Espadas, Donna Laxmisan, Archana Sittig, Dean F. TI Primary care practitioners' views on test result management in EHR-enabled health systems: a national survey SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ELECTRONIC MEDICAL-RECORD; PHYSICIAN ORDER ENTRY; FOLLOW-UP; INFORMATION-TECHNOLOGY; RESPONSE RATES; DIAGNOSTIC ERROR; NOTIFICATION; COMMUNICATION; QUESTIONNAIRES; IMPLEMENTATION AB Context Failure to notify patients of test results is common even when electronic health records (EHRs) are used to report results to practitioners. We sought to understand the broad range of social and technical factors that affect test result management in an integrated EHR-based health system. Methods Between June and November 2010, we conducted a cross-sectional, web-based survey of all primary care practitioners (PCPs) within the Department of Veterans Affairs nationwide. Survey development was guided by a socio-technical model describing multiple inter-related dimensions of EHR use. Findings Of 5001 PCPs invited, 2590 (51.8%) responded. 55.5% believed that the EHRs did not have convenient features for notifying patients of test results. Over a third (37.9%) reported having staff support needed for notifying patients of test results. Many relied on the patient's next visit to notify them for normal (46.1%) and abnormal results (20.1%). Only 45.7% reported receiving adequate training on using the EHR notification system and 35.1% reported having an assigned contact for technical assistance with the EHR; most received help from colleagues (60.4%). A majority (85.6%) stayed after hours or came in on weekends to address notifications; less than a third reported receiving protected time (30.1%). PCPs strongly endorsed several new features to improve test result management, including better tracking and visualization of result notifications. Conclusions Despite an advanced EHR, both social and technical challenges exist in ensuring notification of test results to practitioners and patients. Current EHR technology requires significant improvement in order to avoid similar challenges elsewhere. C1 [Singh, Hardeep; Petersen, Nancy J.; Sawhney, Mona K.; Smith, Michael W.; Murphy, Daniel R.; Espadas, Donna; Laxmisan, Archana] Baylor Coll Med, Dept Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep; Petersen, Nancy J.; Sawhney, Mona K.; Smith, Michael W.; Murphy, Daniel R.; Espadas, Donna; Laxmisan, Archana] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Spitzmueller, Christiane] Univ Houston, Dept Psychol, Houston, TX USA. [Sittig, Dean F.] Univ Texas Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), Baylor Coll Med, Dept Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr 152,Sect Hl, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU Department of Veterans Affairs National Center for Patient Safety; Houston VA HSR&D Center of Excellence [HFP90-020]; National Library of Medicine [R01 LM006942]; Office of the National Coordinator for Health Information Technology (ONC) [10510592] FX The research reported here was supported by the Department of Veterans Affairs National Center for Patient Safety and in part by the Houston VA HSR&D Center of Excellence (HFP90-020), the National Library of Medicine (R01 LM006942), and the Office of the National Coordinator for Health Information Technology (ONC #10510592). NR 60 TC 15 Z9 15 U1 1 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2013 VL 20 IS 4 BP 727 EP 735 DI 10.1136/amiajnl-2012-001267 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 161CJ UT WOS:000320168600019 PM 23268489 ER PT J AU Zlatar, ZZ Towler, S McGregor, KM Dzierzewski, JM Bauer, A Phan, S Cohen, M Marsiske, M Manini, TM Crosson, B AF Zlatar, Zvinka Z. Towler, Stephen McGregor, Keith M. Dzierzewski, Joseph M. Bauer, Andrew Phan, Stephanie Cohen, Matthew Marsiske, Michael Manini, Todd M. Crosson, Bruce TI Functional Language Networks in Sedentary and Physically Active Older Adults SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Cognitive aging; Physical activity; Functional magnetic resonance imaging; Semantic fluency; Attention network; Transcranial magnetic stimulation ID AGE-DIFFERENCES; BRAIN ACTIVITY; FITNESS; OPTIMIZATION; REGISTRATION; COGNITION; TMS/FMRI; IMAGES; CORTEX; MEMORY AB Functional magnetic resonance imaging (fMRI) studies have identified consistent age-related changes during various cognitive tasks, such that older individuals display more positive and less negative task-related activity than young adults. Recently, evidence shows that chronic physical exercise may alter aging-related changes in brain activity; however, the effect of exercise has not been studied for the neural substrates of language function. Additionally, the potential mechanisms by which aging alters neural recruitment remain understudied. To address these points, the present study enrolled elderly adults who were either sedentary or physically active to characterize the neural correlates of language function during semantic fluency between these groups in comparison to a young adult sample. Participants underwent fMRI during semantic fluency and transcranial magnetic stimulation to collect the ipsilateral silent period, a measure of interhemispheric inhibition. Results indicated that sedentary older adults displayed reductions in negative task-related activity compared to the active old group in areas of the attention network. Longer interhemispheric inhibition was associated with more negative task-related activity in the right and left posterior perisylvian cortex, suggesting that sedentary aging may result in losses in task facilitatory cortical inhibition. However, these losses may be mitigated by regular engagement in physical exercise. C1 [Zlatar, Zvinka Z.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Towler, Stephen; McGregor, Keith M.; Crosson, Bruce] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Towler, Stephen; Crosson, Bruce] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [McGregor, Keith M.; Crosson, Bruce] Atlanta Vet Affairs Med Ctr, RR&D Ctr Excellence, Decatur, GA USA. [Dzierzewski, Joseph M.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Dzierzewski, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bauer, Andrew; Phan, Stephanie] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Cohen, Matthew; Marsiske, Michael] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. [Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. RP Zlatar, ZZ (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr MC 0664, La Jolla, CA 92093 USA. EM zzlatar@ucsd.edu RI Crosson, Bruce/L-3128-2013; Meijer, Anna/K-5118-2016; OI Marsiske, Michael/0000-0001-5973-2116; McGregor, Keith/0000-0003-3654-351X FU National Institutes on Aging (NIA) [P30 AG028740-03, T32 AG020499-08, F31 AG 032802 01A1]; Department of Veteran Affairs Office of Academic Affairs Predoctoral Fellowship; VA Rehabilitation R&D Center of Excellence [F2182C]; Senior Research Career Scientist awards [B6364L] FX This work was supported by the National Institutes on Aging (NIA) through awards: P30 AG028740-03 (ZZ), T32 AG020499-08 (ZZ), F31 AG 032802 01A1 (JD); the Department of Veteran Affairs Office of Academic Affairs Predoctoral Fellowship (KMM); the VA Rehabilitation R&D Center of Excellence F2182C (BC); and Senior Research Career Scientist awards B6364L (BC). The authors gratefully acknowledge the assistance of staff and participants. The authors report no actual or potential conflicts of interest. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 40 TC 7 Z9 7 U1 0 U2 8 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 JUL PY 2013 VL 19 IS 6 BP 625 EP 634 DI 10.1017/S1355617713000246 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 170QY UT WOS:000320869700001 PM 23458438 ER PT J AU Conrad, MF Baloum, V Mukhopadhyay, S Garg, A Patel, VI Cambria, RP AF Conrad, Mark F. Baloum, Valy Mukhopadhyay, Shankha Garg, Ashu Patel, Virendra I. Cambria, Richard P. TI Progression of asymptomatic carotid stenosis despite optimal medical therapy SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 21-23, 2012 CL Boston, MA SP New England Soc Vasc Surg ID TRANSIENT ISCHEMIC ATTACK; ASSOCIATION/AMERICAN STROKE ASSOCIATION; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; ARTERY STENOSIS; CARDIOVASCULAR HEALTH; VASCULAR EVENTS; DISEASE; PREVENTION; ENDARTERECTOMY AB Background: Despite level 1 evidence in support of carotid endarterectomy vs medical therapy in selected asymptomatic patients, an alternative posture is that optimal medical therapy (OMT) has not been adequately studied and that such OMT has reduced stroke risk in asymptomatic patients to levels wherein carotid endarterectomy is no longer justified. The goal of this study was to determine the natural history of patients with asymptomatic moderate (50%-69%) carotid artery stenosis (AMCAS) in a contemporary cohort as a function of their associated medical therapy. Methods: Patients with AMCAS determined by duplex ultrasound (DUS) from 2005-2006 were identified in our hospital database. Patients were included in the cohort if they had at least one additional DUS during the 6-year follow-up interval. Patient characteristics including medication history and lipid levels were collected. Patients were considered to have OMT if they were on aspirin and a statin with a low-density lipoprotein level that was always <100 mg/dL. Study end points included progression of carotid disease by DUS to severe stenosis (70%-100%), development of ipsilateral neurologic symptoms (INS) such as stroke or transient ischemic attack, and death. Results: There were 900 carotid arteries in 794 patients in the study cohort. The average age was 72.5 years, 77.2% had hypertension, 59.6% had coronary artery disease, and 87.1% were on a statin throughout the study. The low-density lipoprotein cholesterol level was always normal (<100 mg/dL) in 37.8% and accordingly, 241 (30.3%) had OMT as defined above. The 5-year actuarial survival was 81.9% +/- 1.3% with no advantage seen with OMT. Multivariate analysis of survival showed statins were protective (hazard ratio [HR], 0.50; confidence interval [CI], 0.34-0.73; P = .0004). The 5-year freedom from plaque progression was 61.2% +/- 2.1% with no benefit from OMT vs the control group. Multivariate predictors of plaque progression were chronic kidney disease (HR, 2.1; CI, 1.2-3.7; P = .009), aspirin use (HR, 1.9; CI, 1.2-3.0; P = .01), and the use of calcium channel blockers (HR, 1.4; CI, 1.1-1.8; P = .007). There were 90 (11.3%) patients who developed INS during follow-up (58% of these were strokes), and the 5-year freedom from INS was 88.4% 6 1.5%. Multivariate predictors of INS were diabetes (HR, 2.3; CI, 1.5-3.6; P = .0002) and warfarin use (HR, 1.9; CI, 1.2-2.9; P = .009); while statin use (HR, 0.37; CI, 0.22-0.65; P = .0005) was protective against symptom development. Conclusions: At the 5-year of follow-up, OMT failed to prevent carotid disease progression or development of ipsilateral symptoms in 45% of patients with AMCAS. C1 [Conrad, Mark F.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Conrad, Mark F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Conrad, MF (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, WAC 440,15 Parkman St, Boston, MA 02114 USA. EM mconrad@partners.org NR 38 TC 23 Z9 25 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2013 VL 58 IS 1 BP 128 EP + DI 10.1016/j.jvs.2013.04.002 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 172ZY UT WOS:000321048300021 PM 23806255 ER PT J AU Jin, YM Liu, RJ Xie, JY Xiong, HB He, JCJ Chen, N AF Jin, Yuanmeng Liu, Ruijie Xie, Jingyuan Xiong, Huabao He, John Cijiang Chen, Nan TI Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model SO LABORATORY INVESTIGATION LA English DT Article DE fibrosis; inflammation; interleukin-10; kidney; unilateral ureteral obstruction ID NF-KAPPA-B; RENAL-DISEASE; IN-VIVO; IL-10; CELLS; GENE; EXPRESSION; MICE; PANCREATITIS; MACROPHAGES AB Interleukin-10 functions as a general immunosuppressive cytokine, which also negatively regulates inflammatory responses through complex mechanisms. Recent studies suggested that IL-10 may also inhibit fibrosis in various diseased models. However, the role of IL-10 in renal fibrosis has not been demonstrated. Here, we investigated the effects of IL-10 in the development of renal tubulointerstitial fibrosis by creating the unilateral ureteral obstruction (UUO) model in IL-10 knockout (-/-) mice. We performed sham or unilateral ureteral obstruction surgery in 8-week-old IL-10 -/- male mice and age and sex-matched wild type littermates. Mice were killed at 7 days or 14 days post surgery and renal tissues were obtained for RNA, protein, and immunohistochemical analysis. Our results found IL-10 deficiency resulted in enhanced renal fibrosis demonstrated by more severe tubular injury and collagen deposition and higher expression of pro-fibrotic genes (including alpha-SMA, MMP-2, fibronectin, FSP-1 and vimentin). Our results also found IL-10-/- UUO mice developed more severe renal inflammation with a significant increase in inflammatory cells infiltration, and upregulation of inflammatory chemokines (MCP-1 and RANTES), and cytokines (TNF-alpha, IL-6, IL-8, and M-CSF). Further study revealed that enhanced renal inflammation and fibrosis was associated with significantly increased activation of both TGF-beta/Smad3 and NF-kappa B signaling pathways. In summary, our study provides the direct evidence that IL-10 is an endogenous cytokine that has a key role in protecting against development of renal inflammation and fibrosis. Enhancement of IL-10 expression could be a potential anti-fibrosis therapy for patients with chronic kidney diseases. C1 [Jin, Yuanmeng; Xie, Jingyuan; Chen, Nan] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Nephrol, Shanghai 200030, Peoples R China. [Liu, Ruijie; He, John Cijiang] Mt Sinai Sch Med, Div Nephrol, Dept Med, New York, NY 10029 USA. [Liu, Ruijie; He, John Cijiang] James J Peters Vet Adm Med Ctr, New York, NY USA. [Xiong, Huabao] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY USA. RP He, JCJ (reprint author), Mt Sinai Sch Med, Div Nephrol, Dept Med, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu; chen-nan@medmail.com.cn FU National Basic Research Program of China 973 [2012CB517600, 2012CB517604]; National key technology R&D Program (12-5) [2011BAI10B00, 2011BAI10B06]; National Natural Science Foundation of China [81070568, 81000295, 81200526] FX This work is the result of a collaborative effort between the Nephrology Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China and the Nephrology Division of Mount Sinai Hospital, New York, USA. This work is supported by National Basic Research Program of China 973, program No. 2012CB517600 (No.2012CB517604), National key technology R&D Program (12-5), program NO. 2011BAI10B00 (2011BAI10B06), National Natural Science Foundation of China (No. 81070568), National Natural Science Foundation of China (No. 81000295) and National Natural Science Foundation of China (No. 81200526). NR 42 TC 15 Z9 16 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 2013 VL 93 IS 7 BP 801 EP 811 DI 10.1038/labinvest.2013.64 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 172XD UT WOS:000321039100006 PM 23628901 ER PT J AU Knox, CJ Hohman, MH Kleiss, IJ Weinberg, JS Heaton, JT Hadlock, TA AF Knox, Christopher J. Hohman, Marc H. Kleiss, Ingrid J. Weinberg, Julie S. Heaton, James T. Hadlock, Tessa A. TI Facial nerve repair: Fibrin Adhesive Coaptation versus Epineurial Suture Repair in a Rodent Model SO LARYNGOSCOPE LA English DT Article DE Fibrin adhesive; rodent; facial nerve; neurorrhaphy ID WHISKER MOVEMENTS; RATS; ANASTOMOSIS; SURGERY; SEALANT; MOTOR; HEAD; GLUE AB Objectives/Hypothesis Repair of the transected facial nerve has traditionally been accomplished with microsurgical neurorrhaphy; however, fibrin adhesive coaptation (FAC) of peripheral nerves has become increasingly popular over the past decade. We compared functional recovery following suture neurorrhaphy to FAC in a rodent facial nerve model. Study Design Prospective, randomized animal study. Methods Sixteen rats underwent transection and repair of the facial nerve proximal to the pes anserinus. Eight animals underwent epineurial suture (ES) neurorrhaphy, and eight underwent repair with fibrin adhesive (FA). Surgical times were documented for all procedures. Whisking function was analyzed on a weekly basis for both groups across 15 weeks of recovery. Results Rats experienced whisking recovery consistent in time course and degree with prior studies of rodent facial nerve transection and repair. There were no significant differences in whisking amplitude, velocity, or acceleration between suture and FA groups. However, the neurorrhaphy time with FA was 70% shorter than for ES (P < 0.05). Conclusion Although we found no difference in whisking recovery between suture and FA repair of the main trunk of the rat facial nerve, the significantly shorter operative time for FA repair makes this technique an attractive option. The relative advantages of both techniques are discussed. C1 [Knox, Christopher J.; Hohman, Marc H.; Kleiss, Ingrid J.; Weinberg, Julie S.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kleiss, Ingrid J.] Radboud Univ Nijmegen, Med Ctr, Dept Otolaryngol Head & Neck Surg, NL-6525 ED Nijmegen, Netherlands. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu FU National Institutes of Health [RO1NS071067] FX This study was supported by the National Institutes of Health grant number RO1NS071067. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 20 TC 7 Z9 7 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2013 VL 123 IS 7 BP 1618 EP 1621 DI 10.1002/lary.23885 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 169ML UT WOS:000320784300011 PM 23188676 ER PT J AU Lozano, JNJ Vacas-Jacques, P Anderson, RR Franco, W AF Lozano, Joel N. Jimenez Vacas-Jacques, Paulino Anderson, R. Rox Franco, Walfre TI Effect of Fibrous Septa in Radiofrequency Heating of Cutaneous and Subcutaneous Tissues: Computational Study SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE skin; fat; hypodermis; cellulite; electrothermolysis; heat transfer; hyperthermia ID BIOLOGICAL TISSUES; CELLULITE; FAT; SKIN AB Background and Objectives Radiofrequency (RF) energy exposure is a popular non-invasive method for generating heat within cutaneous and subcutaneous tissues. Subcutaneous fat consists of fine collagen fibrous septa meshed with clusters of adipocytes having distinct structural, electrical and thermal properties that affect the distribution and deposition of RF energy. The objectives of this work are to (i) determine the electric and thermal effects of the fibrous septa in the RF heating; (ii) investigate the RF heating of individual fat lobules enclosed by fibrous septa; and, (iii) discuss the clinical implications. Methods and Results We used the finite element method to model the two-dimensional, time-dependent, electro-thermal response of a three-layer tissue (skin, subcutaneous fat, and muscle). We considered two different configurations of subcutaneous fat tissue: a homogenous layer of fat only and a honeycomb-like layer of fat with septa. Architecture of the fibrous septa was anatomically accurate, constructed from sagittal images from human micro-MRI. For a large electrode applied to the skin surface, results show that the absorbed electric power density is greater in some septa than in the surrounding fat lobules, favoring the flux of electric current density. Fibers aligned parallel to the electric field have higher electric flux and, consequently, absorb more power. Heat transfer from the septa occurs over time during and after RF energy delivery. There is a greater temperature rise in fat with fibrous septa. Conclusions The presence of septa affects the local distribution of the static electric field, facilitates the flux of electric current and enhances the bulk electric power absorption of the subcutaneous fat layer. Fibrous septa aligned with the local electric field have higher absorbed power density than septa oriented perpendicular to the electric field. Individual fat lobules gain heat instantly by local power absorption and, eventually, by diffusion from the surrounding septa. Lasers Surg. Med. 45:326-338, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Lozano, Joel N. Jimenez; Vacas-Jacques, Paulino; Anderson, R. Rox; Franco, Walfre] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Franco, W (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. EM wfranco@partners.org FU American Society for Laser Medicine and Surgery (ASLMS) FX P. Vacas-Jacques gratefully acknowledges the American Society for Laser Medicine and Surgery (ASLMS) for funding of travel expenses to attend the ASLMS 2012 Annual Conference. NR 23 TC 7 Z9 7 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD JUL PY 2013 VL 45 IS 5 BP 326 EP 338 DI 10.1002/lsm.22146 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA 169KX UT WOS:000320780200006 ER PT J AU Golberg, A Yarmush, ML Konry, T AF Golberg, Alexander Yarmush, Martin L. Konry, Tania TI Picoliter droplet microfluidic immunosorbent platform for point-of-care diagnostics of tetanus SO MICROCHIMICA ACTA LA English DT Article DE Droplet microfluidics; Point-of-care diagnostics; Biosensor microsphere; Tetanus immunization status ID FLOW; CHIP; PCR AB We have developed a sensitive, specific, rapid and low cost picoliter microsphere-based platform for bioanalyte detection and quantification. In this method, a biological sample, biosensing microspheres, and fluorescently labeled detection (secondary) antibodies are co-encapsulated to capture the analyte (here: human anti-tetanus immunoglobulin G) on the surface of the microsphere in microfluidic pL-sized droplets. The absorption of the analyte and detecting antibodies on the microsphere concentrate the fluorescent signal in correlation with analyte concentration. Using our platform and commercially available antibodies, we were able to quantify anti-tetanus antibodies in human serum. In comparison to standard bulk immunosorbent assays, the microfluidic droplet platform presented here reduces the reagent volume by four orders of magnitude, while fast reagent mixing reduces the detection time from hours to minutes. We consider this platform to be a major leap forward in the miniaturization of immunosorbent assays and to provide a rapid and low cost tool for global point-of-care. C1 [Golberg, Alexander; Yarmush, Martin L.; Konry, Tania] Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Sch Med, Boston, MA 02114 USA. [Golberg, Alexander; Yarmush, Martin L.; Konry, Tania] Shriners Burns Inst, Boston, MA 02114 USA. RP Konry, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Sch Med, 55 Blossom St, Boston, MA 02114 USA. EM konry.tania@gmail.com OI Golberg, Alexander/0000-0001-8782-8879 FU ECOR postdoctoral award; Shriners Grant [85120-BOS] FX This work was supported in part by the ECOR postdoctoral award to AG and Shriners Grant #85120-BOS. We are also thankful to Dr. Jon F. Edd for the help in design of the array. NR 28 TC 7 Z9 7 U1 3 U2 42 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0026-3672 J9 MICROCHIM ACTA JI Microchim. Acta PD JUL PY 2013 VL 180 IS 9-10 BP 855 EP 860 DI 10.1007/s00604-013-0998-3 PG 6 WC Chemistry, Analytical SC Chemistry GA 170OH UT WOS:000320862100016 ER PT J AU El Khattabi, I Sharma, A AF El Khattabi, Ilham Sharma, Arun TI Preventing p38 MAPK-Mediated MafA Degradation Ameliorates beta-Cell Dysfunction under Oxidative Stress SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTORS; CATENIN DEGRADATION; INSULIN-SECRETION; IN-VIVO; PHOSPHORYLATION; GLUCOSE; STABILITY; EXPRESSION AB The reduction in the expression of glucose-responsive insulin gene transcription factor MafA accompanies the development of beta-cell dysfunction under oxidative stress/diabetic milieu. Humans with type 2 diabetes have reduced MafA expression, and thus preventing this reduction could overcome beta-cell dysfunction and diabetes. We previously showed that p38 MAPK, but not glycogen synthase kinase 3 (GSK3), is a major regulator of MafA degradation under oxidative stress. Here, we examined the mechanisms of this degradation and whether preventing MafA degradation under oxidative stress will overcome beta-cell dysfunction. We show that under oxidative and nonoxidative conditions p38 MAPK directly binds to MafA and triggers MafA degradation via ubiquitin proteasomal pathway. However, unlike nonoxidative conditions, MafA degradation under oxidative stress depended on p38 MAPK-mediated phosphorylation at threonine (T) 134, and not T57. Furthermore the expression of alanine (A) 134-MafA, but not A57-MafA, reduced the oxidative stress-mediated loss of glucose-stimulated insulin secretion, which was independent of p38 MAPK action on protein kinase D, a regulator of insulin secretion. Interestingly, the expression of proteasomal activator PA28 gamma that degrades GSK3-phosphorylated (including T57) MafA was reduced under oxidative stress, explaining the dominance of p38 MAPK over the GSK3 pathway in regulating MafA stability under oxidative stress. These results identify two distinct pathways mediating p38 MAPK-dependent MafA degradation under oxidative and non-oxidative conditions and show that inhibiting MafA degradation under oxidative stress ameliorates beta-cell dysfunction and could lead to novel therapies for diabetes. C1 [El Khattabi, Ilham; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. RP Sharma, A (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM arun.sharma@joslin.harvard.edu FU National Institutes of Health (NIH) [RO1 DK060127, ADA]; Herbert Graetz Fund; Shirley and William Fleisher Family Foundation; Alexander and Margaret Stewart Trust; NIH [T32 DK07260]; NIH, Diabetes Endocrinology Research Center [DK-36836] FX This study was supported by research grants from National Institutes of Health (NIH) Grant RO1 DK060127 and ADA, the Herbert Graetz Fund, Shirley and William Fleisher Family Foundation, and the Alexander and Margaret Stewart Trust. I. E. K. was supported by a postdoctoral fellowship from NIH Grant T32 DK07260. We acknowledge support from NIH DK-36836 Diabetes Endocrinology Research Center grant for Media and Assay cores. NR 52 TC 5 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 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2013 VL 27 IS 7 BP 1078 EP 1090 DI 10.1210/me.2012-1346 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173TG UT WOS:000321101700006 PM 23660596 ER PT J AU Stewart, SE Yu, D Scharf, JM Neale, BM Fagerness, JA Mathews, CA Arnold, PD Evans, PD Gamazon, ER Osiecki, L McGrath, L Haddad, S Crane, J Hezel, D Illman, C Mayerfeld, C Konkashbaev, A Liu, C Pluzhnikov, A Tikhomirov, A Edlund, CK Rauch, SL Moessner, R Falkai, P Maier, W Ruhrmann, S Grabe, HJ Lennertz, L Wagner, M Bellodi, L Cavallini, MC Richter, MA Cook, EH Kennedy, JL Rosenberg, D Stein, DJ Hemmings, SMJ Lochner, C Azzam, A Chavira, DA Fournier, E Garrido, H Sheppard, B Umana, P Murphy, DL Wendland, JR Veenstra-VanderWeele, J Denys, D Blom, R Deforce, D Van Nieuwerburgh, F Westenberg, HGM Walitza, S Egberts, K Renner, T Miguel, EC Cappi, C Hounie, AG do Rosario, MC Sampaio, AS Vallada, H Nicolini, H Lanzagorta, N Camarena, B Delorme, R Leboyer, M Pato, CN Pato, MT Voyiaziakis, E Heutink, P Cath, DC Posthuma, D Smit, JH Samuels, J Bienvenu, OJ Cullen, B Fyer, AJ Grados, MA Greenberg, BD McCracken, JT Riddle, MA Wang, Y Coric, V Leckman, JF Bloch, M Pittenger, C Eapen, V Black, DW Ophoff, RA Strengman, E Cusi, D Turiel, M Frau, F Macciardi, F Gibbs, JR Cookson, MR Singleton, A Hardy, J Crenshaw, AT Parkin, MA Mirel, DB Conti, DV Purcell, S Nestadt, G Hanna, GL Jenike, MA Knowles, JA Cox, N Pauls, DL AF Stewart, S. E. Yu, D. Scharf, J. M. Neale, B. M. Fagerness, J. A. Mathews, C. A. Arnold, P. D. Evans, P. D. Gamazon, E. R. Osiecki, L. McGrath, L. Haddad, S. Crane, J. Hezel, D. Illman, C. Mayerfeld, C. Konkashbaev, A. Liu, C. Pluzhnikov, A. Tikhomirov, A. Edlund, C. K. Rauch, S. L. Moessner, R. Falkai, P. Maier, W. Ruhrmann, S. Grabe, H-J Lennertz, L. Wagner, M. Bellodi, L. Cavallini, M. C. Richter, M. A. Cook, E. H., Jr. Kennedy, J. L. Rosenberg, D. Stein, D. J. Hemmings, S. M. J. Lochner, C. Azzam, A. Chavira, D. A. Fournier, E. Garrido, H. Sheppard, B. Umana, P. Murphy, D. L. Wendland, J. R. Veenstra-VanderWeele, J. Denys, D. Blom, R. Deforce, D. Van Nieuwerburgh, F. Westenberg, H. G. M. Walitza, S. Egberts, K. Renner, T. Miguel, E. C. Cappi, C. Hounie, A. G. do Rosario, M. Conceicao Sampaio, A. S. Vallada, H. Nicolini, H. Lanzagorta, N. Camarena, B. Delorme, R. Leboyer, M. Pato, C. N. Pato, M. T. Voyiaziakis, E. Heutink, P. Cath, D. C. Posthuma, D. Smit, J. H. Samuels, J. Bienvenu, O. J. Cullen, B. Fyer, A. J. Grados, M. A. Greenberg, B. D. McCracken, J. T. Riddle, M. A. Wang, Y. Coric, V. Leckman, J. F. Bloch, M. Pittenger, C. Eapen, V. Black, D. W. Ophoff, R. A. Strengman, E. Cusi, D. Turiel, M. Frau, F. Macciardi, F. Gibbs, J. R. Cookson, M. R. Singleton, A. Hardy, J. Crenshaw, A. T. Parkin, M. A. Mirel, D. B. Conti, D. V. Purcell, S. Nestadt, G. Hanna, G. L. Jenike, M. A. Knowles, J. A. Cox, N. Pauls, D. L. CA North Amer Brain Expression Consor UK Brain Expression Database TI Genome-wide association study of obsessive-compulsive disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE DLGAP; genetic; genomic; GWAS; neurodevelopmental disorder; obsessive-compulsive disorder ID OCD COLLABORATIVE GENETICS; FAMILY-BASED ASSOCIATION; QUANTITATIVE TRAIT LOCI; TRANSPORTER GENE; LINKAGE; SLC1A1; SNPS; TWIN; REPLICATION; EXPRESSION AB Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P = 2.49 x 10(-6) and P = 3.44 x 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value = 3.84 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P < 0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P = 0.001) was observed within the top-ranked SNPs (P < 0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. C1 [Stewart, S. E.; Yu, D.; Scharf, J. M.; Neale, B. M.; Fagerness, J. A.; Osiecki, L.; McGrath, L.; Haddad, S.; Crane, J.; Hezel, D.; Illman, C.; Mayerfeld, C.; Purcell, S.; Jenike, M. A.; Pauls, D. L.] Harvard Univ, Sch Med, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Stewart, S. E.; Yu, D.; Scharf, J. M.; Fagerness, J. A.; Osiecki, L.; McGrath, L.; Haddad, S.; Crane, J.; Hezel, D.; Illman, C.; Mayerfeld, C.; Purcell, S.; Jenike, M. A.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stewart, S. E.] Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada. [Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scharf, J. M.; Purcell, S.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Neale, B. M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Scharf, J. M.; Neale, B. M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Mathews, C. A.; Azzam, A.; Sheppard, B.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Arnold, P. D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Arnold, P. D.; Richter, M. A.; Kennedy, J. L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Evans, P. D.; Gamazon, E. R.; Konkashbaev, A.; Pluzhnikov, A.; Tikhomirov, A.; Cox, N.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Liu, C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Edlund, C. K.; Conti, D. V.] Univ So Calif, Zilkha Neurogenet Inst, Keck Sch Med, Dept Preventat Med,Div Biostat, Los Angeles, CA USA. [Edlund, C. K.; Conti, D. V.] Univ So Calif, Keck Sch Med, Epigenome Ctr, Los Angeles, CA 90033 USA. [Rauch, S. L.] Partners Psychiat, Boston, MA USA. [Rauch, S. L.] McLean Hosp, Boston, MA USA. [Moessner, R.; Maier, W.; Lennertz, L.; Wagner, M.] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Falkai, P.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany. [Ruhrmann, S.] Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany. [Grabe, H-J] Univ Med Greifswald, Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Bellodi, L.] Psychiat Univ Vita Salute San Raffaele, Milan, Italy. [Cavallini, M. C.] Fdn Ctr San Raffaele Monte Tabor, Milan, Italy. [Richter, M. A.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Toronto, ON M4N 3M5, Canada. [Cook, E. H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. [Kennedy, J. L.] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Rosenberg, D.] Wayne State Univ, Detroit, MI USA. [Rosenberg, D.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Stein, D. J.] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Hemmings, S. M. J.; Lochner, C.] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. [Chavira, D. A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Fournier, E.; Garrido, H.; Umana, P.] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Murphy, D. L.; Wendland, J. R.] NIMH, Lab Clin Sci, Intramural Res Program, Bethesda, MD 20892 USA. [Wendland, J. R.] F Hoffmann Roche Ltd, CNS Clin Biomarker Grp, Pharma Res & Early Dev, Basel, Switzerland. [Veenstra-VanderWeele, J.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN 37235 USA. [Veenstra-VanderWeele, J.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Pediat, Nashville, TN 37235 USA. [Veenstra-VanderWeele, J.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Pharmacol, Nashville, TN 37235 USA. [Veenstra-VanderWeele, J.] Vanderbilt Univ, Inst Brain, Nashville, TN 37235 USA. [Denys, D.; Blom, R.; Westenberg, H. G. M.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Denys, D.; Blom, R.; Westenberg, H. G. M.] Netherlands Inst Neurosci, Amsterdam, Netherlands. [Deforce, D.; Van Nieuwerburgh, F.] Univ Ghent, Lab Pharmaceut Biotechnol, B-9000 Ghent, Belgium. [Walitza, S.] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. [Egberts, K.; Renner, T.] Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-97070 Wurzburg, Germany. [Miguel, E. C.; Cappi, C.; Hounie, A. G.; do Rosario, M. Conceicao; Sampaio, A. S.; Vallada, H.] Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo, Brazil. [Sampaio, A. S.] Univ Fed Bahia, Univ Hlth Care Serv SMURB, Salvador, BA, Brazil. [Nicolini, H.] Univ Mexico City, Ctr Genom Sci, Mexico City, DF, Mexico. [Nicolini, H.; Lanzagorta, N.] Carracci Med Grp, Mexico City, DF, Mexico. [Camarena, B.] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Depto Genet Psiquiatr, Mexico City, DF, Mexico. [Delorme, R.; Leboyer, M.] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, INSERM,U955, F-75019 Paris, France. [Delorme, R.; Leboyer, M.] Inst Mondor Rech Biomed, Creteil, France. [Delorme, R.; Leboyer, M.] French Natl Sci Fdn, Fdn Fondamental, Creteil, France. [Pato, C. N.; Pato, M. T.; Voyiaziakis, E.; Knowles, J. A.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Heutink, P.; Posthuma, D.] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Clin Genet, Sect Med Gen, Amsterdam, Netherlands. [Cath, D. C.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Utrecht, Netherlands. [Cath, D. C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [Cath, D. C.; Smit, J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, Utrecht, Netherlands. [Samuels, J.; Bienvenu, O. J.; Cullen, B.; Grados, M. A.; Riddle, M. A.; Wang, Y.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [McCracken, J. T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Coric, V.; Leckman, J. F.; Bloch, M.; Pittenger, C.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Coric, V.; Bloch, M.; Pittenger, C.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Eapen, V.] Univ New S Wales, Acad Unit Child Psychiat, South West Sydney AUCS, Sydney, NSW, Australia. [Black, D. W.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA. [Ophoff, R. A.; Strengman, E.] UCLA Ctr Neurobehav Genet, Los Angeles, CA USA. [Ophoff, R. A.; Strengman, E.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Cusi, D.; Frau, F.] Univ Milan, Grad Sch Nephrol, Dept Med Surg & Dent, Milan, Italy. [Cusi, D.] San Paolo Hosp, Div Nephrol, Milan, Italy. [Turiel, M.] Univ Milan, Dept Hlth Technol, Milan, Italy. [Frau, F.] Filarete Fdn, Milan, Italy. [Macciardi, F.] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Gibbs, J. R.; Cookson, M. R.; Singleton, A.] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Hardy, J.] UCL, Dept Mol Neurosci, Inst Neurol, London, England. [Crenshaw, A. T.; Parkin, M. A.; Mirel, D. B.; Purcell, S.] Broad Inst Harvard MIT, Cambridge, MA USA. RP Stewart, SE (reprint author), Univ British Columbia, Dept Psychiat, OCD Clin, BCMHARI,CFRI, A3-118,938 West 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM sevelynstewart@gmail.com; dpauls@pngu.mgh.harvard.edu RI Macciardi, Fabio/N-3768-2014; Wagner, Michael/E-2325-2011; Stein, Dan/A-1752-2008; Trabzuni, Daniah/C-4034-2012; Singleton, Andrew/C-3010-2009; Weale, Michael/F-2587-2010; Stewart, Evelyn/K-6961-2014; Van Nieuwerburgh, Filip/H-9697-2015; Veenstra-VanderWeele, Jeremy/K-1935-2015; Vallada, Homero/D-1333-2014; Traynor, Bryan/G-5690-2010; Renner, Tobias/I-2120-2013; Hardy, John/C-2451-2009; Deforce, Dieter/J-4725-2013; SAMPAIO, ALINE/M-1229-2013 OI Hemmings, Sian/0000-0001-8461-1017; Zonderman, Alan B/0000-0002-6523-4778; Gamazon, Eric/0000-0003-4204-8734; Lanzagorta, Nuria/0000-0001-6769-6813; Stewart, S. Evelyn/0000-0002-0994-6383; Macciardi, Fabio/0000-0003-0537-4266; Wagner, Michael/0000-0003-2589-6440; Stein, Dan/0000-0001-7218-7810; Trabzuni, Daniah/0000-0003-4826-9570; Nicolini, Humberto/0000-0003-2494-0067; Hanna, Gregory/0000-0002-0742-6990; Samuels, Jack/0000-0002-6715-7905; Azzam, Amin/0000-0002-7024-7450; Walitza, Susanne/0000-0002-8161-8683; Weale, Michael/0000-0003-4593-1186; Van Nieuwerburgh, Filip/0000-0001-8815-5485; Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Vallada, Homero/0000-0001-5123-8295; Deforce, Dieter/0000-0002-0635-661X; SAMPAIO, ALINE/0000-0001-5568-6167 FU Judah Foundation; NIH [MH079489, MH073250]; American Recovery and Re-investment Act (ARRA) awards [NS40024-07S1, NS16648-29S1]; American Academy of Child and Adolescent Psychiatry (AACAP); Anxiety Disorders Association of America (ADAA); University of British Columbia; Michael Smith Foundation Clinical Research Scholar Award; Tourette Syndrome Association; American Academy of Neurology Foundation; National Center for Research Resources [RR020278]; NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' [HHSN268200782096C]; UK Medical Research Council; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000932-02] FX The authors would like to express their utmost gratitude to the OCD-affected families who participated in this research. In addition, they would like to thank the International OCD Foundation (IOCDF) for their role in establishing the IOCDF Genetics Collaborative, as well as other individuals who played roles in assisting this study, including Rhonda Ellwyn, Katherine Beattie, Colm O'Dushlaine, Doug Ruderfer, Priya Moorjani and V. Guttenthaler. This work was supported primarily by a grant from the Judah Foundation (a private, non-industry related foundation established by a family affected by OCD), NIH grants MH079489 and MH073250 to DLP, American Recovery and Re-investment Act (ARRA) awards NS40024-07S1 and NS16648-29S1 to DLP, by an American Academy of Child and Adolescent Psychiatry (AACAP) Early Investigator Research Grant, an Anxiety Disorders Association of America (ADAA) Junior Investigator Research Grant, the University of British Columbia and a Michael Smith Foundation Clinical Research Scholar Award to SES, and grants from the Tourette Syndrome Association (DLP and JMS), the American Academy of Neurology Foundation (JMS) and NIH grant MH085057 to JMS. The Broad Institute Center for Genotyping and Analysis was supported by grant U54 RR020278 from the National Center for Research Resources. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for related genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). The data sets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi/study_id = phs000092.v1.p1 through dbGaP accession number phs000092.v1.p. Frontal lobe eQTL data was provided by the North American Brain Expression Consortium and the UK Human Brain Expression Database. Funding support for generation of the eQTL data was provided by the UK Medical Research Council and the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services project Z01 AG000932-02. The North American Brain Expression Consortium comprises: Sampath Arepalli, Mark R Cookson, Allissa Dillman, Luigi Ferrucci, J Raphael Gibbs, Dena G Hernandez, Robert Johnson, Dan L Longo, Michael A Nalls, Richard O0Brien, Andrew Singleton, Bryan Traynor, Juan Troncoso, Marcel van der Brug, H Ronald Zielke and Alan Zonderman.; The UK Human Brain Expression Database membership comprises: John A Hardy, Mina Ryten, Colin Smith, Daniah Trabzuni, Robert Walker and Mike Weale. None of the funding sources supporting this work had any influence or played any role in: (a) the design or conduct of the study; (b) management, analysis or interpretation of the data; or c) preparation, review or approval of the manuscript. NR 71 TC 76 Z9 79 U1 4 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 2013 VL 18 IS 7 BP 788 EP 798 DI 10.1038/mp.2012.85 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 168NL UT WOS:000320712700012 PM 22889921 ER PT J AU Bovenberg, MSS Degeling, MH Tannous, BA AF Bovenberg, M. Sarah S. Degeling, M. Hannah Tannous, Bakhos A. TI Cell-based Immunotherapy Against Gliomas: From Bench to Bedside SO MOLECULAR THERAPY LA English DT Review ID PLURIPOTENT STEM-CELLS; ACUTE MYELOID-LEUKEMIA; LONG-TERM SURVIVAL; T-CELLS; ADOPTIVE IMMUNOTHERAPY; DENDRITIC CELLS; CLINICAL-TRIAL; GROWTH-FACTOR; BRAIN-TUMORS; GLIOBLASTOMA-MULTIFORME AB Glioblastoma (GBM) comprises 51% of all gliomas and is the most malignant form of brain tumors with a median survival of 18-21 months. Standard-of-care treatment includes maximal surgical resection of the tumor mass in combination with radiation and chemotherapy. However, as the poor survival rate indicates, these treatments have not been effective in preventing disease progression. Cellular immunotherapy is currently being explored as therapeutic approach to treat malignant brain tumors. In this review, we discuss advances in active, passive, and vaccine-based immunotherapeutic strategies for gliomas both at the bench and in the clinic. C1 [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Neurosci Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Institutes of Health; National Institute of Neurological Disorders and Stroke [1R01NS064983]; National Cancer Institute [1R01CA166077]; Fulbright scholarship; Saal van Zwanenberg Foundation; VSB fonds; Dr. Hendrik Muller Vaderlandsch Fonds; Dutch Cancer Foundation (KWF Kankerbestrijding); Hersenstichting brain fund; Huygens Scholarship Program; Jo Keur (Leiden hospital) FX Dr Tannous is supported by grants from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke (1R01NS064983), and the National Cancer Institute (1R01CA166077). M. H. D. is supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSB fonds, Dr. Hendrik Muller Vaderlandsch Fonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), the Hersenstichting brain fund as well as the Jo Keur (Leiden hospital). M. S. S. B. was supported by a Fulbright scholarship, the Huygens Scholarship Program, VSB Fonds, and the Saal van Zwanenberg Foundation. The authors thank Grant Lewandrowski for editorial assistance. The authors declared no conflict of interest. NR 67 TC 4 Z9 4 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2013 VL 21 IS 7 BP 1297 EP 1305 DI 10.1038/mt.2013.80 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 173WL UT WOS:000321112500004 PM 23648695 ER PT J AU Wheeler, LA Vrbanac, V Trifonova, R Brehm, MA Gilboa-Geffen, A Tanno, S Greiner, DL Luster, AD Tager, AM Lieberman, J AF Wheeler, Lee Adam Vrbanac, Vladimir Trifonova, Radiana Brehm, Michael A. Gilboa-Geffen, Adi Tanno, Serah Greiner, Dale L. Luster, Andrew D. Tager, Andrew M. Lieberman, Judy TI Durable Knockdown and Protection From HIV Transmission in Humanized Mice Treated With Gel-formulated CD4 Aptamer-siRNA Chimeras SO MOLECULAR THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; SMALL INTERFERING RNAS; IN-VIVO DELIVERY; PREEXPOSURE PROPHYLAXIS; RHESUS MACAQUES; BLT MICE; INHIBITION; PREVENTION; CCR5; CELLS AB The continued spread of HIV underscores the need to interrupt transmission. One attractive strategy, in the absence of an effective vaccine, is a topical microbicide, but the need for application around the time of sexual intercourse leads to poor patient compliance. Intravaginal (IVAG) application of CD4 aptamer-siRNA chimeras (CD4-AsiCs) targeting the HIV coreceptor CCR5, gag, and vif protected humanized mice from sexual transmission. In non-dividing cells and tissue, RNAi-mediated gene knockdown lasts for several weeks, providing an opportunity for infrequent dosing not temporally linked to sexual intercourse, when compliance is challenging. Here, we investigate the durability of gene knockdown and viral inhibition, protection afforded by CCR5 or HIV gene knockdown on their own, and effectiveness of CD4-AsiCs formulated in a gel in polarized human cervicovaginal explants and in humanized mice. CD4-AsiC-mediated gene knockdown persisted for several weeks. Cell-specific gene knockdown and protection were comparable in a hydroxyethylcellulose gel formulation. CD4-AsiCs against CCR5 or gag/vif performed as well as a cocktail in humanized mice. Transmission was completely blocked by CCR5 CD4-AsiCs applied 2 days before challenge. Significant, but incomplete, protection also occurred when exposure was delayed for 4 or 6 days. CD4-AsiCs targeting gag/vif provided some protection when administered only after exposure. These data suggest that CD4-AsiCs are a promising approach for developing an HIV microbicide. C1 [Wheeler, Lee Adam; Trifonova, Radiana; Gilboa-Geffen, Adi; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wheeler, Lee Adam; Trifonova, Radiana; Gilboa-Geffen, Adi; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Vrbanac, Vladimir; Tanno, Serah; Luster, Andrew D.; Tager, Andrew M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vrbanac, Vladimir; Tanno, Serah; Luster, Andrew D.; Tager, Andrew M.] Harvard Univ, Sch Med, Boston, MA USA. [Brehm, Michael A.; Greiner, Dale L.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Lieberman, J (reprint author), 200 Longwood Ave,Warren Alpert Bldg 255, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu RI Lieberman, Judy/A-2717-2015; gilboa-geffen, adi/E-3028-2013 OI gilboa-geffen, adi/0000-0001-9549-4194 FU NIH [AI090671, AI078897, AI46629]; Harvard CFAR [AI060354]; Ragon Institute; Cancer Research Institute; Adelstein Fellowship; Harvard Medical School MD/PhD Program; Point Foundation FX This work was supported by grants from the NIH (AI090671, J.L.; AI078897, A. M. T., A. D. L.; AI46629, D. L. G., M. A. B.), the Harvard CFAR (AI060354, A. M. T., A. D. L.), and Ragon Institute (J.L., A. M. T., A. D. L.) and fellowships from the Cancer Research Institute, Adelstein Fellowship, Harvard Medical School MD/PhD Program and Point Foundation (L. A. W.), and Harvard CFAR (R. T.). We thank T Allen and T Dudek and the Ragon Institute Virology Core for providing viral stocks for in vivo studies and E Oliva, M Miri, and A Bodo, MGH Surgical Pathology and L Yang, BIDMC for tissue specimens. NR 50 TC 34 Z9 36 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2013 VL 21 IS 7 BP 1378 EP 1389 DI 10.1038/mt.2013.77 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 173WL UT WOS:000321112500012 PM 23629001 ER PT J AU Kay, KR Smith, C Wright, AK Serrano-Pozo, A Pooler, AM Koffie, R Bastin, ME Bak, TH Abrahams, S Kopeikina, KJ McGuone, D Frosch, MP Gillingwater, TH Hyman, BT Spires-Jones, TL AF Kay, Kevin R. Smith, Colin Wright, Ann K. Serrano-Pozo, Alberto Pooler, Amy M. Koffie, Robert Bastin, Mark E. Bak, Thomas H. Abrahams, Sharon Kopeikina, Katherine J. McGuone, Declan Frosch, Matthew P. Gillingwater, Thomas H. Hyman, Bradley T. Spires-Jones, Tara L. TI Studying synapses in human brain with array tomography and electron microscopy SO NATURE PROTOCOLS LA English DT Article ID OLIGOMERIC AMYLOID-BETA; ALZHEIMERS-DISEASE; MOUSE MODEL; ACCUMULATION; TAUOPATHY; PATHOLOGY; NEURONS; PLAQUES; MICE AB Postmortem studies of synapses in human brain are problematic because of the axial resolution limit of light microscopy and the difficulty in preserving and analyzing ultrastructure with electron microscopy (EM). Array tomography (AT) overcomes these problems by embedding autopsy tissue in resin and cutting ribbons of ultrathin serial sections. Ribbons are imaged with immunofluorescence, allowing high-throughput imaging of tens of thousands of synapses to assess synapse density and protein composition. The protocol takes similar to 3 d per case, excluding image analysis, which is done at the end of the study. Parallel processing for transmission electron microscopy (TEM) using a protocol modified to preserve the structure in human samples allows complementary ultrastructural studies. Incorporation of AT and TEM into brain banking is a potent way of phenotyping synapses in well-characterized clinical cohorts in order to develop clinicopathological correlations at the synapse level. This will be important for research in neurodegenerative disease, developmental disease and psychiatric illness. C1 [Kay, Kevin R.; Serrano-Pozo, Alberto; Pooler, Amy M.; Koffie, Robert; Kopeikina, Katherine J.; Frosch, Matthew P.; Hyman, Bradley T.; Spires-Jones, Tara L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Kay, Kevin R.; Serrano-Pozo, Alberto; Pooler, Amy M.; Koffie, Robert; Kopeikina, Katherine J.; Frosch, Matthew P.; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [Wright, Ann K.; Bastin, Mark E.; Bak, Thomas H.; Abrahams, Sharon; Gillingwater, Thomas H.] Univ Edinburgh, Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland. [Pooler, Amy M.] Kings Coll London, Dept Neurosci, Inst Psychiat, London WC2R 2LS, England. [McGuone, Declan; Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [McGuone, Declan; Frosch, Matthew P.] Harvard Univ, Sch Med, Boston, MA USA. RP Spires-Jones, TL (reprint author), Massachusetts Gen Hosp, Charlestown, MA USA. EM tara.spires@marshallscholarship.org OI Spires-Jones, Tara/0000-0003-2530-0598; Gillingwater, Thomas/0000-0002-0306-5577; SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU US National Institutes of Health (NIH) [R00AG033670, T32AG000277, P50AG05134]; Alzheimer's Research UK; Sylvia Aitken Charitable Trust; Medical Research Council UK [G110616] FX We thank the patients and their families for their generous donations. We also thank K. Micheva and S. Smith for training us in the AT technique; D. Selkoe (Harvard Medical School), V. Lee (University of Pennsylvania) and D. Walsh (Harvard Medical School) for antibodies; and K. Kuchibhotla and S. Raymond for MATLAB programming. Harvard Catalyst supplied biostatistical support. This work was supported by US National Institutes of Health (NIH) grants R00AG033670 (T.L.S.-J., K.R.K.), T32AG000277 (K.J.K., B.T.H.), P50AG05134 (B.T.H., A.S.-P., M.P.F.); Alzheimer's Research UK (A.M.P.), the Sylvia Aitken Charitable Trust (C.S., A.K.W., M.E.B., T.H.B., S.A., T.H.G.) and the Medical Research Council UK G110616 (C.S.). NR 36 TC 17 Z9 17 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD JUL PY 2013 VL 8 IS 7 BP 1366 EP 1380 DI 10.1038/nprot.2013.078 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 172LI UT WOS:000321004300008 PM 23787894 ER PT J AU Kalva, SP Athanasoulis, CA AF Kalva, Sanjeeva P. Athanasoulis, Christos A. TI DEVICE THERAPY Variation in the use of inferior vena cava filters for VTE SO NATURE REVIEWS CARDIOLOGY LA English DT Editorial Material ID EXPERIENCE AB Wide variation exists in the use of inferior vena cava filters for the treatment of venous thromboembolism, possibly because of a deficit of evidence on the efficacy of these devices, and a lack of consensus on their use. Future guidelines should be evidence-based and account for the development of novel anticoagulants. C1 [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Athanasoulis, Christos A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, GRB-297,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 9 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 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD JUL PY 2013 VL 10 IS 7 BP 368 EP 370 DI 10.1038/nrcardio.2013.65 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 169FI UT WOS:000320763800002 PM 23629435 ER PT J AU Loeffler, JS Durante, M AF Loeffler, Jay S. Durante, Marco TI Charged particle therapy-optimization, challenges and future directions SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CARBON-ION RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; PROTON-BEAM THERAPY; CANCER STEM-CELLS; CONFORMAL RADIATION-THERAPY; RECURRENT RECTAL-CANCER; RELATIVE BIOLOGICAL EFFECTIVENESS; RANDOMIZED CONTROLLED-TRIAL; CURRENT CLINICAL-EVIDENCE; RISK PROSTATE-CANCER AB The use of charged particle therapy to control tumours non-invasively offers advantages over conventional radiotherapy. Protons and heavy ions deposit energy far more selectively than X-rays, allowing a higher local control of the tumour, a lower probability of damage to healthy tissue, low risk of complications and the chance for a rapid recovery after therapy. Charged particles are also useful for treating tumours located in areas that surround tissues that are radiosensitive and in anatomical sites where surgical access is limited. Current trial outcomes indicate that accelerated ions can potentially replace surgery for radical cancer treatments, which might be beneficial as the success of surgical cancer treatments are largely dependent on the expertise and experience of the surgeon and the location of the tumour. However, to date, only a small number of controlled randomized clinical trials have made comparisons between particle therapy and X-rays. Therefore, although the potential advantages are clear and supported by data, the cost: benefit ratio remains controversial. Research in medical physics and radiobiology is focusing on reducing the costs and increasing the benefits of this treatment. C1 [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Loeffler, Jay S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Durante, Marco] GSI Helmholtzzentrum Schwerionenforsch, Dept Biophys, D-64291 Darmstadt, Germany. [Durante, Marco] Tech Univ Darmstadt, D-64291 Darmstadt, Germany. RP Durante, M (reprint author), GSI Helmholtzzentrum Schwerionenforsch, Dept Biophys, Plackstr 1, D-64291 Darmstadt, Germany. EM m.durante@gsi.de RI Durante, Marco/K-1315-2014; OI Durante, Marco/0000-0002-4615-553X NR 160 TC 102 Z9 105 U1 8 U2 57 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 JUL PY 2013 VL 10 IS 7 BP 411 EP 424 DI 10.1038/nrclinonc.2013.79 PG 14 WC Oncology SC Oncology GA 172NB UT WOS:000321009700008 PM 23689752 ER PT J AU Solovieff, N Cotsapas, C Lee, PH Purcell, SM Smoller, JW AF Solovieff, Nadia Cotsapas, Chris Lee, Phil H. Purcell, Shaun M. Smoller, Jordan W. TI Pleiotropy in complex traits: challenges and strategies SO NATURE REVIEWS GENETICS LA English DT Review ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; GENERALIZED ESTIMATING EQUATIONS; ELECTRONIC MEDICAL-RECORDS; BREAST-CARCINOMA CELLS; GENETIC ASSOCIATION; SUSCEPTIBILITY LOCI; RISK LOCI; PRINCIPAL-COMPONENTS; PHENOME-WIDE AB Genome-wide association studies have identified many variants that each affects multiple traits, particularly across autoimmune diseases, cancers and neuropsychiatric disorders, suggesting that pleiotropic effects on human complex traits may be widespread. However, systematic detection of such effects is challenging and requires new methodologies and frameworks for interpreting cross-phenotype results. In this Review, we discuss the evidence for pleiotropy in contemporary genetic mapping studies, new and established analytical approaches to identifying pleiotropic effects, sources of spurious cross-phenotype effects and study design considerations. We also outline the molecular and clinical implications of such findings and discuss future directions of research. C1 [Solovieff, Nadia; Lee, Phil H.; Purcell, Shaun M.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Solovieff, Nadia; Lee, Phil H.; Purcell, Shaun M.; Smoller, Jordan W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Solovieff, Nadia; Lee, Phil H.; Purcell, Shaun M.; Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Cotsapas, Chris] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Cotsapas, Chris] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Cotsapas, Chris] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Purcell, Shaun M.] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY 10029 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu OI Cotsapas, Chris/0000-0002-7772-5910 FU US National Institute of Mental Health (NIMH) [R01-MH079799, K24MH094614] FX This work was supported in part by the US National Institute of Mental Health (NIMH) grants R01-MH079799 and K24MH094614 (both to J.W.S.). NR 133 TC 171 Z9 171 U1 7 U2 69 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD JUL PY 2013 VL 14 IS 7 BP 483 EP 495 DI 10.1038/nrg3461 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 165UF UT WOS:000320510000009 PM 23752797 ER PT J AU Cha, TD An, HS AF Cha, Thomas D. An, Howard S. TI Cervical spine manifestations in patients with inflammatory arthritides SO NATURE REVIEWS RHEUMATOLOGY LA English DT Review ID SOMATOSENSORY-EVOKED-POTENTIALS; ATLANTO-AXIAL SUBLUXATION; TERM FOLLOW-UP; RHEUMATOID-ARTHRITIS; ANKYLOSING-SPONDYLITIS; LONG-TERM; NATURAL-HISTORY; MYELOPATHY; LESIONS; MANAGEMENT AB The cervical spine can frequently become involved in patients with rheumatologic disorders, as a result of either the rheumatologic disease itself or age-associated degenerative processes that can also occur in the rest of the population. Awareness of the increased risk of cervical spine manifestations in patients with rheumatologic disorders enables early recognition and initiation of the appropriate treatment regimen. For example, patients with rheumatoid arthritis (RA) often have spinal instability which, if left untreated, can lead to neurological deficits. Biologic agents are effective in slowing the progression of the skeletal abnormality as well as for treating the RA, and this approach is often sufficient. However, early surgical intervention is recommended for patients with RA who develop neurologic deficits, as conservative approaches have limited effectiveness in this group. Spinal stability should be the primary surgical objective. For patients with ankylosing spondylitis, cervical spine surgery might be required either for fracture repair or to correct severe kyphosis. Understanding each condition's specific cervical spine manifestation and its natural history can help to clarify the appropriate indications for and timing of surgery to maximize patients' outcomes and limit complications. C1 [Cha, Thomas D.] Massachusetts Gen Hosp, Dept Orthoped Surg, Spine Div, Boston, MA 02114 USA. [An, Howard S.] Rush Univ, Med Ctr, Dept Orthoped Surg, Spine Div, Chicago, IL 60612 USA. RP Cha, TD (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Spine Div, 55 Fruit St,Yawkey Suite 3800, Boston, MA 02114 USA. EM tcha@partners.org NR 55 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4790 J9 NAT REV RHEUMATOL JI Nat. Rev. Rheumatol. PD JUL PY 2013 VL 9 IS 7 BP 423 EP 432 DI 10.1038/nrrheum.2013.40 PG 10 WC Rheumatology SC Rheumatology GA 175TZ UT WOS:000321257700007 PM 23528639 ER PT J AU Kong, L Lee, JH Doores, KJ Murin, CD Julien, JP McBride, R Liu, Y Marozsan, A Cupo, A Klasse, PJ Hoffenberg, S Caulfield, M King, CR Hua, YZ Le, KM Khayat, R Deller, MC Clayton, T Tien, H Feizi, T Sanders, RW Paulson, JC Moore, JP Stanfield, RL Burton, DR Ward, AB Wilson, IA AF Kong, Leopold Lee, Jeong Hyun Doores, Katie J. Murin, Charles D. Julien, Jean-Philippe McBride, Ryan Liu, Yan Marozsan, Andre Cupo, Albert Klasse, Per-Johan Hoffenberg, Simon Caulfield, Michael King, C. Richter Hua, Yuanzi Le, Khoa M. Khayat, Reza Deller, Marc C. Clayton, Thomas Tien, Henry Feizi, Ten Sanders, Rogier W. Paulson, James C. Moore, John P. Stanfield, Robyn L. Burton, Dennis R. Ward, Andrew B. Wilson, Ian A. TI Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY PG9; STRUCTURAL BASIS; POTENT; BROAD; RECOGNITION; EPITOPE; SITE; EVOLUTION; TRIMERS AB A substantial proportion of the broadly neutralizing antibodies (bnAbs) identified in certain HIV-infected donors recognize glycan-dependent epitopes on HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332 glycan-dependent epitope from its 3.1-angstrom crystal structure with gp120, CD4 and Fab 17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield and access the gp120 protein surface. EM reveals that PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. Combined structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent antigenic region is highly accessible and much more extensive than initially appreciated, which allows for multiple binding modes and varied angles of approach; thereby it represents a supersite of vulnerability for antibody neutralization. C1 [Kong, Leopold; Lee, Jeong Hyun; Murin, Charles D.; Julien, Jean-Philippe; Hua, Yuanzi; Khayat, Reza; Deller, Marc C.; Clayton, Thomas; Tien, Henry; Stanfield, Robyn L.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Kong, Leopold; Doores, Katie J.; Julien, Jean-Philippe; Hua, Yuanzi; Le, Khoa M.; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Doores, Katie J.; Le, Khoa M.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Doores, Katie J.; Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Cambridge, MA USA. [Doores, Katie J.; Burton, Dennis R.] Harvard Univ, Cambridge, MA 02138 USA. [McBride, Ryan; Paulson, James C.] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA. [Liu, Yan; Feizi, Ten] Univ London Imperial Coll Sci Technol & Med, Dept Med, Glycosci Lab, London, England. [Marozsan, Andre; Cupo, Albert; Klasse, Per-Johan; Sanders, Rogier W.; Moore, John P.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Hoffenberg, Simon; Caulfield, Michael; King, C. Richter] Int AIDS Vaccine Initiat, Design & Dev Lab, Brooklyn, NY USA. [Deller, Marc C.; Clayton, Thomas; Tien, Henry] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA. [Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Burton, DR (reprint author), Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. EM burton@scripps.edu; abward@scripps.edu; wilson@scripps.edu RI Ward, Andrew/F-9203-2014; Liu, Yan/D-9117-2013; Koyuncu, ayfer/M-3872-2015; OI Ward, Andrew/0000-0001-7153-3769; Feizi, Ten/0000-0001-6495-0329; Doores, Katie/0000-0002-5507-1725 FU Wellcome Trust [WT093378MA, WT099197MA]; UK Research Councils' Basic Technology Initiative 'Glycoarrays' [GRS/79268]; UK Engineering and Physical Sciences Research Council Translational grant [EP/G037604/1]; US National Cancer Institute (NCI) Alliance of Glycobiologists for Detection of Cancer and Cancer Risk [U01 CA128416]; US National Institutes of Health (NIH) through the National Center for Research Resources' P41 program at the National Center for Research Resources [RR017573]; NIH [P30 AI036214]; NIH National Institute of General Medical Sciences (NIGMS); Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences of the US Department of Energy (DOE) [DE-AC02-05CH11231]; DOE, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; NCI [Y1-CO-1020]; NIGMS [Y1-GM-1104]; International AIDS Vaccine Initiative Neutralizing Antibody Center; Center for HIV/AIDS Vaccine Immunology [CHAVI-ID UM1 AI100663]; HIV Vaccine Research and Design program [P01 AI82362, R37 AI36082]; University of California, San Diego, Center for AIDS Research; NIH, US National Institute of Allergy and Infectious Disease; NIH, NCI; NIH, US National Institute of Mental Health; NIH, US National Institute on Drug Abuse; NIH, US National Institute of Child Health and Human Development; NIH, US National Institute of Heart, Lung and Blood; NIH, US National Institute of Aging; NIH RO1 grants [AI84817, AI33292]; Joint Center of Structural Genomics by the NIH NIGMS Protein Structure Initiative [U54 GM094586]; American Foundation for AIDS Research Mathilde Krim Fellowship in Basic Biomedical Research FX We thank X. Dai for help with data processing; J. Chittuluru for assistance with the 2D PCA; D. Ekiert for initial cloning of PGT 135; R. Pejchal for initial cloning of soluble CD4 and the gp 120 JR-FL core construct; C. Poulsen and R. Wyatt from The Scripps Research Institute, La Jolla, California, USA for donation of 17b IgG; C. Arnold from the UK National Institute for Biological Standards and Control, Health Protection Agency for donation of ARP3119 monoclonal antibody CA13; M. Elsliger for computer support; C. Corbaci for help with preparing figures and movies; A. Irimia, C. Blattner and M. Hong for discussions; J. P. Verenini for help in manuscript formatting; and W. Koff for discussions and support. We also thank S. C. Arzberger from ADA Technologies (Littleton, Colorado, USA), J. Zhang, currently at Life Bioscience (Aurora, Colorado, USA), and ADA Technologies for supplying the high-density NHS-activated slides used for glycan microarray analysis; members of the Glycosciences Laboratory for their collaboration in the establishment of the neoglycolipid-based microarray system; and T. Butters and colleagues from the University of Oxford, Oxford, UK for the glucosylated N-glycans. Work using the neoglycolipid system is supported by the Wellcome Trust (WT093378MA and WT099197MA) (T. F.), the UK Research Councils' Basic Technology Initiative 'Glycoarrays' (GRS/79268) (T. F.), UK Engineering and Physical Sciences Research Council Translational grant (EP/G037604/1) and US National Cancer Institute (NCI) Alliance of Glycobiologists for Detection of Cancer and Cancer Risk (U01 CA128416) (T. F.). The EM data were collected at the US National Resource for Automated Molecular Microscopy, which is supported by the US National Institutes of Health (NIH) through the National Center for Research Resources' P41 program (RR017573) at the National Center for Research Resources. X-ray data sets were collected at the Advanced Light Source beamline 5.0.2 at the Berkeley Center for Structural Biology (BCSB) and the Advanced Photon Source beamline 23ID-B. The BCSB is supported in part by the NIH, the NIH National Institute of General Medical Sciences (NIGMS) and the Howard Hughes Medical Institute. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences of the US Department of Energy (DOE) under contract no. DE-AC02-05CH11231. Use of the APS was supported by the DOE, Basic Energy Sciences, Office of Science, under contract no. DE-AC02-06CH11357. The GM/CA-CAT 23-ID-B beamline has been funded in whole or in part with federal funds from the NCI (Y1-CO-1020) and NIGMS (Y1-GM-1104). This work was supported by the International AIDS Vaccine Initiative Neutralizing Antibody Center; by the Center for HIV/AIDS Vaccine Immunology (CHAVI-ID UM1 AI100663) (A. B. W., D. R. B. and I. A. W.); by the HIV Vaccine Research and Design program (P01 AI82362 and R37 AI36082) (J. P. M., A. B. W. and I. A. W.); by the University of California, San Diego, Center for AIDS Research (A. B. W.), an NIH-funded program (P30 AI036214) supported by the following NIH institutes and centers: US National Institute of Allergy and Infectious Disease, NCI, US National Institute of Mental Health, US National Institute on Drug Abuse, US National Institute of Child Health and Human Development, US National Institute of Heart, Lung and Blood and US National Institute of Aging; by NIH RO1 grants AI84817 (I. A. W.) and AI33292 (D. R. B.; ); and by the Joint Center of Structural Genomics by the NIH NIGMS Protein Structure Initiative (U54 GM094586) (I. A. W.). A portion of this work was supported by an American Foundation for AIDS Research Mathilde Krim Fellowship in Basic Biomedical Research (L. K.). The content is the responsibility of the authors and does not necessarily reflect the official views of the NIGMS, NCI or NIH. This is manuscript #21722 from The Scripps Research Institute. NR 46 TC 142 Z9 142 U1 5 U2 47 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2013 VL 20 IS 7 BP 796 EP + DI 10.1038/nsmb.2594 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 175SM UT WOS:000321253300007 PM 23708606 ER PT J AU Pancera, M Shahzad-ul-Hussan, S Doria-Rose, NA McLellan, JS Bailer, RT Dai, KF Loesgen, S Louder, MK Staupe, RP Yang, YP Zhang, BS Parks, R Eudailey, J Lloyd, KE Blinn, J Alam, SM Haynes, BF Amin, MN Wang, LX Burton, DR Koff, WC Nabel, GJ Mascola, JR Bewley, CA Kwong, PD AF Pancera, Marie Shahzad-ul-Hussan, Syed Doria-Rose, Nicole A. McLellan, Jason S. Bailer, Robert T. Dai, Kaifan Loesgen, Sandra Louder, Mark K. Staupe, Ryan P. Yang, Yongping Zhang, Baoshan Parks, Robert Eudailey, Joshua Lloyd, Krissey E. Blinn, Julie Alam, S. Munir Haynes, Barton F. Amin, Mohammed N. Wang, Lai-Xi Burton, Dennis R. Koff, Wayne C. Nabel, Gary J. Mascola, John R. Bewley, Carole A. Kwong, Peter D. TI Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; HIV-1 ENVELOPE GLYCOPROTEINS; HAMSTER OVARY CELLS; GLYCOSYLATION SITES; CRYSTAL-STRUCTURE; 2G12 RECOGNIZES; GP120; POTENT; COMPLEX AB HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization. C1 [Pancera, Marie; Doria-Rose, Nicole A.; McLellan, Jason S.; Bailer, Robert T.; Dai, Kaifan; Louder, Mark K.; Staupe, Ryan P.; Yang, Yongping; Zhang, Baoshan; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Shahzad-ul-Hussan, Syed; Loesgen, Sandra; Bewley, Carole A.] NIDDK, Lab Bioorgan Chem, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Blinn, Julie; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Amin, Mohammed N.; Wang, Lai-Xi] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Amin, Mohammed N.; Wang, Lai-Xi] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Cambridge, MA USA. [Burton, Dennis R.] Harvard Univ, Cambridge, MA 02138 USA. [Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY USA. RP Bewley, CA (reprint author), NIDDK, Lab Bioorgan Chem, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; pdkwong@nih.gov FU US National Institutes of Health; International AIDS Vaccine Initiative's Neutralizing Antibody Consortium; Center for HIV AIDS Vaccine Immunology from the US National Institutes of Health [AI 5U19 AI 067854-06]; US National Institutes of Health [1R21 AI101035]; US National Institutes of Health (NIH/NCRR) [P41 RR018502-01]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank J. Stuckey for assistance with figures and members of the Structural Biology Section and Structural Bioinformatics Core, Vaccine Research Center for discussions or comments on the manuscript; A. Kumar for sharing the ELISA binding protocol with biotinylated lectins; P. Azadi and S. Archer-Hartmann, University of Georgia, for performing glycan analyses and glycopeptide mapping; J. Baalwa (Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA), D. Ellenberger (International Laboratory Branch, Division of Global HIV/AIDS, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA), D. Gabuzda (Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA), F. Gao (Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA), B. Hahn (Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA), K. Hong (State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China), J. Kim (US Military HIV Research Program, Henry M. Jackson Foundation, Bethesda, Maryland, USA), F. McCutchan (US Military HIV Research Program, Henry M. Jackson Foundation, Bethesda, Maryland, USA), D. Montefiori (Department of Surgery, Duke University, Durham, North Carolina, USA), L. Morris, (Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa), J. Overbaugh (Program for Appropriate Technology in Health, Seattle, Washington, USA), E. Sanders-Buell (US Military HIV Research Program, Henry M. Jackson Foundation, Bethesda, Maryland, USA), G. Shaw (Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA), R. Swanstrom (University of North Carilina Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA), M. Thomson (University of Birmingham, Birmingham, UK), S. Tovanabutra (Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand), C. Williamson (Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and National Health Laboratory Services, Cape Town, South Africa) and L. Zhang (Department of Public Health, Center for Disease Control and Prevention in Jiangxi Province, Nanchang, China) contributing the HIV-1 Envelope plasmids used in our neutralization panel. Support for this work was provided by the US National Institutes of Health Intramural Research Programs (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases), by grants from the International AIDS Vaccine Initiative's Neutralizing Antibody Consortium and by the Center for HIV AIDS Vaccine Immunology Grant AI 5U19 AI 067854-06 from the US National Institutes of Health (J. E., K. E. L., J. B., S. M. A. and B. F. H.), by US National Institutes of Health grant 1R21 AI101035 (M. N. A. and L-X. W.) and by the US National Institutes of Health (NIH/NCRR)-funded grant P41 RR018502-01 to the Complex Carbohydrate Research Center. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under contract number W-31-109-Eng-38. NR 62 TC 116 Z9 117 U1 1 U2 42 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2013 VL 20 IS 7 BP 804 EP + DI 10.1038/nsmb.2600 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 175SM UT WOS:000321253300008 PM 23708607 ER PT J AU Du, Z Fei, T Verhaak, RGW Su, Z Zhang, Y Brown, M Chen, YW Liu, XS AF Du, Zhou Fei, Teng Verhaak, Roel G. W. Su, Zhen Zhang, Yong Brown, Myles Chen, Yiwen Liu, X. Shirley TI Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID COPY-NUMBER ALTERATION; GENE-EXPRESSION; EXON ARRAYS; CHROMATIN; TRANSCRIPTOME; DISEASE; SEQ; IDENTIFICATION; NETWORK; DIFFERENTIATION AB Despite growing appreciation of the importance of long noncoding RNAs (lncRNAs) in normal physiology and disease, our knowledge of cancer-related lncRNAs remains limited. By repurposing microarray probes, we constructed expression profiles of 10,207 lncRNA genes in approximately 1,300 tumors over four different cancer types. Through integrative analysis of the lncRNA expression profiles with clinical outcome and somatic copy-number alterations, we identified lncRNAs that are associated with cancer subtypes and clinical prognosis and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two newly identified lncRNAs. Our analysis provides a resource of clinically relevant lncRNAs for the development of lncRNA biomarkers and the identification of lncRNA therapeutic targets. It also demonstrates the power of integrating publically available genomic data sets and clinical information for discovering disease-associated lncRNAs. C1 [Du, Zhou; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Fei, Teng; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Fei, Teng; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fei, Teng; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fei, Teng; Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [Fei, Teng; Chen, Yiwen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Fei, Teng; Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Su, Zhen] China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China. RP Liu, XS (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu; ywchen@jimmy.harvard.edu; xsliu@jimmy.harvard.edu RI Zhang, Yong/B-4838-2011; Fei, Teng/G-5324-2015; OI Zhang, Yong/0000-0001-6316-2734; Fei, Teng/0000-0001-5707-0673; Brown, Myles/0000-0002-8213-1658 FU National Natural Science Foundation of China [31028011]; National Basic Research (973) Program of China [2010CB944904]; US National Institutes of Health [GM099409] FX This work was partially funded by the National Natural Science Foundation of China (31028011) (X. S. L.), the National Basic Research (973) Program of China (2010CB944904; Y.Z.) and US National Institutes of Health grant GM099409 (X.S.L.). NR 58 TC 154 Z9 160 U1 4 U2 69 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2013 VL 20 IS 7 BP 908 EP + DI 10.1038/nsmb.2591 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 175SM UT WOS:000321253300021 PM 23728290 ER PT J AU Lee, K Lv, W Ter-Ovanesyan, E Barley, ME Voysey, GE Galea, AM Hirschman, GB Leroy, K Marini, RP Barrett, C Armoundas, AA Cohen, RJ AF Lee, Kichang Lv, Wener Ter-Ovanesyan, Evgeny Barley, Maya E. Voysey, Graham E. Galea, Anna M. Hirschman, Gordon B. Leroy, Kristen Marini, Robert P. Barrett, Conor Armoundas, Antonis A. Cohen, Richard J. TI Cardiac Ablation Catheter Guidance by Means of a Single Equivalent Moving Dipole Inverse Algorithm SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE single equivalent moving dipole; catheter guidance ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CORONARY HEART-DISEASE; VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION; RADIOFREQUENCY ABLATION; ELECTRICAL ACTIVATION; THERAPY; SITES; MODEL; IDENTIFICATION AB Background We developed and evaluated a novel system for guiding radiofrequency catheter ablation therapy of ventricular tachycardia. This guidance system employs an inverse solution guidance algorithm (ISGA) using a single equivalent moving dipole (SEMD) localization method. The method and system were evaluated in both a saline tank phantom model and in vivo animal (swine) experiments. Methods A catheter with two platinum electrodes spaced 3 mm apart was used as the dipole source in the phantom study. A 40-Hz sinusoidal signal was applied to the electrode pair. In the animal study, four to eight electrodes were sutured onto the right ventricle. These electrodes were connected to a stimulus generator delivering 1-ms duration pacing pulses. Signals were recorded from 64 electrodes, located either on the inner surface of the saline tank or on the body surface of the pig, and then processed by the ISGA to localize the physical or bioelectrical SEMD. Results In the phantom studies, the guidance algorithm was used to advance a catheter tip to the location of the source dipole. The distance from the final position of the catheter tip to the position of the target dipole was 2.22 +/- 0.78 mm in real space and 1.38 +/- 0.78 mm in image space (computational space). The ISGA successfully tracked the locations of electrodes sutured on the ventricular myocardium and the movement of an endocardial catheter placed in the animal's right ventricle. Conclusion In conclusion, we successfully demonstrated the feasibility of using an SEMD inverse algorithm to guide a cardiac ablation catheter. C1 [Lee, Kichang; Ter-Ovanesyan, Evgeny; Barley, Maya E.; Cohen, Richard J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lv, Wener] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Voysey, Graham E.; Galea, Anna M.; Hirschman, Gordon B.; Leroy, Kristen] Infoscitex Corp, Waltham, MA USA. [Marini, Robert P.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Barrett, Conor] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Cohen, RJ (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, 45 Carleton St,Room E25-335, Cambridge, MA 02139 USA. EM rjcohen@mit.edu FU NIH [4 R44H L079726-02, 1RO1HL103961]; NIA [1R21AG035128]; Center for Integration of Medicine and Innovative Technology (CIMIT) FX This study was supported by NIH grant (4 R44H L079726-02), by NIA grant 1R21AG035128 and NIH grant 1RO1HL103961. This work was also supported by a Science Award from the Center for Integration of Medicine and Innovative Technology (CIMIT). NR 28 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUL PY 2013 VL 36 IS 7 BP 811 EP 822 DI 10.1111/pace.12114 PG 12 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 174VS UT WOS:000321185400005 PM 23448231 ER PT J AU Guo, L Tsai, SQ Hardison, NE James, AH Motsinger-Reif, AA Thames, B Stone, EA Deng, C Piedrahita, JA AF Guo, L. Tsai, S. Q. Hardison, N. E. James, A. H. Motsinger-Reif, A. A. Thames, B. Stone, E. A. Deng, C. Piedrahita, J. A. TI Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas SO PLACENTA LA English DT Article DE Placenta; Preeclampsia; IUGR; MiR-194; MiR-149 ID INTRAUTERINE GROWTH RESTRICTION; RELATIVE QUANTIFICATION; HYPERTENSION; PREGNANCY; PLASMA; FETAL; MODEL AB Introduction: This study focuses on the implementation of modulated modularity clustering (MMC) a new cluster algorithm for the identification of molecular signatures of preeclampsia and intrauterine growth restriction (IUGR), and the identification of affected microRNAs Methods: Eighty-six human placentas from normal (40), growth-restricted (27), and preeclamptic (19) term pregnancies were profiled using Illumina Human-6 Beadarrays. MMC was utilized to generate modules based on similarities in placental transcriptome. Gene Set Enrichment Analysis (GSEA) was used to predict affected microRNAs. Expression levels of these candidate microRNAs were investigated in seventy-one human term placentas as follows: control (29); IUGR (26); and preeclampsia (16). Results: MMC identified two modules, one representing IUGR placentas and one representing preeclamptic placentas. 326 differentially expressed genes in the module representing IUGR and 889 differentially expressed genes in a module representing preeclampsia were identified. Functional analysis of molecular signatures associated with IUGR identified P13K/AKT, mTOR, p70S6K, apoptosis and IGF-1 signaling as being affected. Analysis of variance of GSEA-predicted microRNAs indicated that miR-194 was significantly down-regulated both in preeclampsia (p = 0.0001) and IUGR (p = 0.0304), and miR-149 was significantly down-regulated in preeclampsia (p = 0.0168). Discussion: Implementation of MMC, allowed identification of genes disregulated in IUGR and preeclampsia. The reliability of MMC was validated by comparing to previous linear modeling analysis of preeclamptic placentas. Conclusion: MMC allowed the elucidation of a molecular signature associated with preeclampsia and a subset of IUGR samples. This allowed the identification of genes, pathways, and microRNAs affected in these diseases. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Guo, L.; Piedrahita, J. A.] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27695 USA. [Guo, L.; Motsinger-Reif, A. A.; Piedrahita, J. A.] N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC USA. [Guo, L.; Deng, C.] Huazhong Agr Univ, Minist Educ, Key Lab Agr Anim Genet Breeding & Reprod, Wuhan, Peoples R China. [Hardison, N. E.; Motsinger-Reif, A. A.; Stone, E. A.] N Carolina State Univ, Dept Stat, Raleigh, NC USA. [Tsai, S. Q.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA 02129 USA. [Tsai, S. Q.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Thames, B.] Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC USA. [James, A. H.] Univ Virginia Hlth Ctr, Dept Obstet & Gynecol, Charlottesville, VA 22908 USA. RP Piedrahita, JA (reprint author), N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, 4700 Hillsborough St, Raleigh, NC 27695 USA. EM jorge_piedrahita@ncsu.edu RI Stone, Eric/Q-7840-2016 FU NIH [HD048510]; Center for Comparative Medicine and Translational Research at the North Carolina State University Collage of Veterinary Medicine FX The authors thank all the women who agreed to participate in this study, which was supported by NIH Grant HD048510 to JP and AJ, and is part of an initiative from the Center for Comparative Medicine and Translational Research at the North Carolina State University Collage of Veterinary Medicine. NR 40 TC 13 Z9 13 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JUL PY 2013 VL 34 IS 7 BP 599 EP 605 DI 10.1016/j.placenta.2013.04.007 PG 7 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 170CL UT WOS:000320827100013 PM 23639576 ER PT J AU Leung, AC Asch, DA Lozada, KN Saynisch, OB Asch, JM Becker, N Griffis, HM Shofer, F Hershey, JC Hill, S Branas, CC Nichol, G Becker, LB Merchant, RM AF Leung, Alison C. Asch, David A. Lozada, Kirkland N. Saynisch, Olivia B. Asch, Jeremy M. Becker, Nora Griffis, Heather M. Shofer, Frances Hershey, John C. Hill, Shawndra Branas, Charles C. Nichol, Graham Becker, Lance B. Merchant, Raina M. TI Where are lifesaving automated external defibrillators located and how hard is it to find them in a large urban city? SO RESUSCITATION LA English DT Article DE AED; Cardiac arrest; CPR; Sudden death; Surveying ID AMERICAN-HEART-ASSOCIATION; PUBLIC-ACCESS DEFIBRILLATION; HOSPITAL CARDIAC-ARREST; IMPROVING SURVIVAL; CARE COMMITTEE; LOCATIONS; MODEL AB Objectives: Automated external defibrillators (AEDs) are lifesaving, but little is known about where they are located or how to find them. We sought to locate AEDs in high employment areas of Philadelphia and characterize the process of door-to-door surveying to identify these devices. Methods: Block groups representing approximately the top 3rd of total primary jobs in Philadelphia were identified using the US Census Local Employment Dynamics database. All buildings within these block groups were surveyed during regular working hours over six weeks during July-August 2011. Buildings were characterized as publically accessible or inaccessible. For accessible buildings, address, location type, and AED presence were collected. Total devices, location description and prior use were gathered in locations with AEDs. Process information (total people contacted, survey duration) was collected for all buildings. Results: Of 1420 buildings in 17 block groups, 949 (67%) were accessible, but most 834 (88%) did not have an AED. 283 AEDs were reported in 115 buildings (12%). 81 (29%) were validated through visualization and 68 (24%) through photo because employees often refused access. In buildings with AEDs, several employees (median 2; range 1-8) were contacted to ascertain information, which required several minutes (mean 4; range 1-55). Conclusions: Door-to-door surveying is a feasible, but time-consuming method for identifying AEDs in high employment areas. Few buildings reported having AEDs and few permitted visualization, which raises concerns about AED access. To improve cardiac arrest outcomes, efforts are needed to improve the availability of AEDs, awareness of their location and access to them. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Asch, David A.; Merchant, Raina M.] Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Branas, Charles C.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. [Nichol, Graham] Univ Washington, Harborview Ctr Prehosp Emergency Care, Seattle, WA 98195 USA. RP Merchant, RM (reprint author), Univ Penn, 423 Guardian St,1022 Blockley Hall, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIH, Physio-Control Seattle, Washington [10714038]; NIH, Zoll Medical, Boston, MA; Cardiac Science, Bothell, Washington; Philips Medical Seattle, Washington; Resuscitation Outcomes Consortium [NIH U01 HL077863-05]; Asmund S. Laerdal Foundation for Acute Medicine; NHLBI [R21 HL093641-01A1, R01 HL089554-03]; Medtronic Foundation; [200211UCT-110607]; [1RC2HL101759-01] FX Merchant: Grant/research support: NIH, K23 Grant 10714038, Pilot funding: Physio-Control Seattle, Washington; Zoll Medical, Boston, MA; Cardiac Science, Bothell, Washington; Philips Medical Seattle, Washington.; Nichol: Institutional grant/research support: Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004-2015; Co-PI, Evaluation of Video Self-Instruction in Compressions-Only CPR (Asmund S. Laerdal Foundation for Acute Medicine) 2007-2010; PI, Randomized Trial of Hemofiltration After Resuscitation from Cardiac Arrest (NHLBI R21 HL093641-01A1) 2009-2011; PI, Randomized Field Trial of Cold Saline IV After Resuscitation from Cardiac Arrest (NHLBI R01 HL089554-03) 2007-2012; Co-I, Resynchronization/Defibrillation for Advanced Heart Failure Trial (RAFT) (200211UCT-110607) 2003-2010; Co-I, Novel Methods of Measuring Health Disparities (1RC2HL101759-01) 2009-2011; Co-I, Cascade Cardiac Resuscitation System (Medtronic Foundation) 2010-2015; PI, Research Collaborator: Gambro Renal Inc., Lakewood, CO, Sotera Wireless, San Diego, CA, Lifebridge Medizintechnik AG, Ampfing, Germany, Other: Chair, AHA Executive Database Steering Committee; Chair, Mission: Lifeline EMS Task Force, Co-Chair, AHA Resuscitation Science Symposium Planning Committee; Member, AHA Advanced Cardiac Life Support Subcommittee; Member, AHA Epidemiology and Statistics Committee; Member, Pacific Mountain Affiliate Board of Directors, American Heart Association, Received travel reimbursement, AHA.; Becker (L): Speaker honoraria/consultant fees: Philips Healthcare, Seattle, WA. Institutional grant/research support: Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, Washington. NR 24 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD JUL PY 2013 VL 84 IS 7 BP 910 EP 914 DI 10.1016/j.resuscitation.2013.01.010 PG 5 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 172IX UT WOS:000320997000016 PM 23357702 ER PT J AU Pan, JD Bredella, MA AF Pan, Judong Bredella, Miriam A. TI Imaging Lesions of the Lateral Hip SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE lateral hip; greater trochanteric pain syndrome; proximal iliotibial band; Morel-Lavallee lesion; meralgia paresthetica ID TROCHANTERIC-PAIN-SYNDROME; RECTUS FEMORIS; MRI FEATURES; DIAGNOSIS; INJURIES AB The lateral aspect of the hip is composed of a complex array of osseous and soft tissue structures. Both common and uncommon clinical entities are encountered in the lateral hip. This article briefly introduces fundamental imaging anatomy and the functional roles of different osseous and soft tissue structures in the lateral aspect of the hip, followed by a discussion of relevant imaging findings of lateral hip pathology. Greater trochanteric pain syndrome is frequently encountered in patients with lateral hip pain and encompasses a spectrum of soft tissue abnormalities including trochanteric and subgluteal bursitis, and tendinopathy or tears of the gluteal tendons. In addition, different types of injuries to the gluteal myotendinous unit and injuries to the indirect head of the rectus femoris, proximal iliotibial band, and the lateral joint capsular ligaments can present with lateral hip pain. Some of the less common soft tissue abnormalities of the lateral hip include Morel-Lavallee lesion and meralgia paresthetica. C1 [Pan, Judong] Radiol Associates Med Grp, San Jose, CA USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org NR 25 TC 4 Z9 4 U1 0 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD JUL PY 2013 VL 17 IS 3 BP 295 EP 305 DI 10.1055/s-0033-1348096 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 168KV UT WOS:000320705500008 PM 23787984 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Prostate Cancer: Where We Have Been, Where We Are, and Where We Are Going SO SEMINARS IN RADIATION ONCOLOGY LA English DT Editorial Material C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2013 VL 23 IS 3 BP 155 EP 156 DI 10.1016/j.semradonc.2013.03.001 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172AL UT WOS:000320972200001 PM 23763880 ER PT J AU Aizer, AA Paly, JJ Efstathiou, JA AF Aizer, Ayal A. Paly, Jonathan J. Efstathiou, Jason A. TI Multidisciplinary Care and Management Selection in Prostate Cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID CONFORMAL RADIATION-THERAPY; QUALITY-OF-LIFE; ACTIVE SURVEILLANCE; RADICAL PROSTATECTOMY; RADIOTHERAPY; ADENOCARCINOMA; TRIAL; ONCOLOGY; OUTCOMES; EXPERIENCE AB The management of prostate cancer is complicated by the multitude of treatment options, the lack of proven superiority of one modality of management, and the presence of physician bias. Care at a multidisciplinary prostate cancer clinic offers patients the relative convenience of consultation with physicians of multiple specialties within the confines of a single visit and appears to serve as a venue in which patients can be counseled regarding the risks and benefits of available therapies in an open and interactive environment. Physician bias may be minimized in such an environment, and patient satisfaction rates are high. Available data suggest that low-risk patients who are seen at a multidisciplinary prostate cancer clinic appear to select active surveillance in greater proportion. However, relatively few studies have investigated the other added value that multidisciplinary clinics provide to the patient or health care system, and therefore, additional studies assessing the impact of multidisciplinary care in the management of patients with prostate cancer are needed. Semin Radiat Oncol 23:157-164 (C) 2013 Published by Elsevier Inc. C1 [Aizer, Ayal A.; Paly, Jonathan J.] Harvard Radiat Oncol Program, Boston, MA USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 51 TC 9 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2013 VL 23 IS 3 BP 157 EP 164 DI 10.1016/j.semradonc.2013.01.001 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172AL UT WOS:000320972200002 PM 23763881 ER PT J AU Tseng, YD Martin, NE AF Tseng, Yolanda D. Martin, Neil E. TI How Can I Help Myself? A Critical Review of Modifiable Behaviors, Medications, and Complementary Alternative Medicine for Men Receiving Radiotherapy for Prostate Cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Review ID RANDOMIZED-CONTROLLED-TRIALS; EXTERNAL-BEAM RADIOTHERAPY; ANDROGEN DEPRIVATION THERAPY; QUALITY-OF-LIFE; RADIATION-THERAPY; AEROBIC EXERCISE; DAILY ASPIRIN; PC-SPES; CIGARETTE-SMOKING; BETA-CAROTENE AB Men receiving radiation for prostate cancer frequently want to know what steps they can take to optimize their chance of cure and reduce their risk of side effects. A variety of modifiable behaviors, medications, and complementary alternative medicine interventions have been investigated in this regard. In this review, we summarize data on tobacco use, exercise, statins and aspirin, and vitamins. There is limited randomized data supporting any of the interventions and additional studies are needed before clinicians can confidently inform their patients regarding what steps to take to improve their outcomes. Semin Radiat Oncol 23:173-181 (C) 2013 Published by Elsevier Inc. C1 [Tseng, Yolanda D.] Harvard Radiat Oncol Program, Boston, MA USA. [Martin, Neil E.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Martin, Neil E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Martin, NE (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB-I,L2, Boston, MA 02115 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 55 TC 0 Z9 0 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2013 VL 23 IS 3 BP 173 EP 181 DI 10.1016/j.semradonc.2013.01.003 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172AL UT WOS:000320972200004 PM 23763883 ER PT J AU Parekh, A Graham, PL Nguyen, PL AF Parekh, Arti Graham, Powell L. Nguyen, Paul L. TI Cancer Control and Complications of Salvage Local Therapy After Failure of Radiotherapy for Prostate Cancer: A Systematic Review SO SEMINARS IN RADIATION ONCOLOGY LA English DT Review ID INTENSITY FOCUSED ULTRASOUND; EXTERNAL-BEAM RADIOTHERAPY; DOSE-RATE BRACHYTHERAPY; ANDROGEN DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; FOLLOW-UP; CRYOSURGICAL ABLATION; COLUMBIA EXPERIENCE; BIOCHEMICAL FAILURE AB The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities. Semin Radiat Oncol 23:222-234 (C) 2013 Elsevier Inc. All rights reserved. C1 [Parekh, Arti; Graham, Powell L.; Nguyen, Paul L.] 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, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 76 TC 21 Z9 21 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2013 VL 23 IS 3 BP 222 EP 234 DI 10.1016/j.semradonc.2013.01.006 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172AL UT WOS:000320972200010 PM 23763889 ER PT J AU Bergman, J Lorenz, KA Acquah-Asare, S Scales, CD Ryan, G Saigal, CS Bennett, CJ Litwin, MS AF Bergman, Jonathan Lorenz, Karl A. Acquah-Asare, Sadie Scales, Charles D. Ryan, Gery Saigal, Christopher S. Bennett, Carol J. Litwin, Mark S. TI Urologist Attitudes Toward End-of-life Care SO UROLOGY LA English DT Article ID CENTERED MEDICAL HOME; PALLIATIVE CARE; QUALITY; HEALTH; CANCER; COMMUNICATION; ASSOCIATIONS; PRIORITIES; PROVIDERS; SUPPORT AB OBJECTIVE To examine urology trainees' views about the quality and current practices of end-of-life care and to explore strategies for improving integration and quality of care. METHODS We conducted semi-structured interviews with 20 trainees from 4 institutions in different regions of the United States. Open-ended questions allowed participants to express themselves independently, and follow-up discussions explored their perception of current end-of-life practices, as well as avenues for future integration and improvement. We analyzed transcripts using a multistage, cutting-and-sorting technique in an inductive approach based on grounded theory analysis. RESULTS Clinicians agreed that their patients do not currently receive ideal care and were interested in joining a team geared towards improving care at the end of life. They expressed a preference for a multidisciplinary team, although the precise role each wanted to play within the team varied. Better identification of depression, pain, and patient-centered goals to allow value-congruent care were high in priorities for improvement. Trainees cited the lack of an educational curriculum on end-of-life care as a barrier to improving care and expressed a desire for formal education on this topic. CONCLUSION Urology trainees believe that end-of-life care can be improved and are interested in participating as part of a multidisciplinary team to better care for these individuals. There was consensus that end-of-life care should be formally taught to all intern and resident physicians and care at the end of life should be integrated to pursue value-congruent care for each patient. UROLOGY 82: 48-52, 2013. (C) 2013 Elsevier Inc. C1 [Bergman, Jonathan] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM jbergman@mednet.ucla.edu NR 30 TC 2 Z9 2 U1 4 U2 9 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 JUL PY 2013 VL 82 IS 1 BP 48 EP 52 DI 10.1016/j.urology.2013.01.040 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 172WK UT WOS:000321036200017 PM 23676360 ER PT J AU Prasad, SM Bennett, CL AF Prasad, Sandip M. Bennett, Charles L. TI Patient Demographics, Quality of Life, and Disease Features of Men With Newly Diagnosed Prostate Cancer: Trends in the PSA Era EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material C1 [Prasad, Sandip M.] Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. [Prasad, Sandip M.] Med Univ S Carolina, Ralph Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. [Bennett, Charles L.] South Carolina Coll Pharm, Charleston, SC USA. [Bennett, Charles L.] Wm Jennings Bryan Dorn VA Med Ctr, Columbia, SC USA. [Bennett, Charles L.] Hollings Canc Ctr, Charleston, SC USA. [Bennett, Charles L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Bennett, Charles L.] Univ S Carolina, Charleston, SC USA. RP Prasad, SM (reprint author), Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. NR 4 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 0090-4295 J9 UROLOGY JI Urology PD JUL PY 2013 VL 82 IS 1 BP 66 EP 66 DI 10.1016/j.urology.2013.01.073 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 172WK UT WOS:000321036200022 PM 23706256 ER PT J AU Liu, DP Zhou, XH AF Liu, Danping Zhou, Xiao-Hua TI ROC Analysis in Biomarker Combination with Covariate Adjustment SO ACADEMIC RADIOLOGY LA English DT Article DE Biomarker combination; covariate adjustment; AUC; covariate standardization ID OPERATING CHARACTERISTIC CURVE; REGRESSION; ACCURACY; MARKERS; AREA AB Rational and Objectives: Receiver operating characteristic (ROC) analysis is often used to find the optimal combination of biomarkers. When the subject level covariates affect the magnitude and/or accuracy of the biomarkers, the combination rule should take into account of the covariate adjustment. The authors propose two new biomarker combination methods that make use of the covariate information. Materials and Methods: The first method is to maximize the area under the covariate-adjusted ROC curve (AAUC). To overborne the limitations of the AAUC measure, the authors further proposed the area under covariate-standardized ROC curve (SAUC), which is an extension of the covariate-specific ROC curve. With a series of simulation studies, the proposed optimal AAUC and SAUC methods are compared with the optimal AUC method that ignores the covariates. The biomarker combination methods are illustrated by an example from Alzheimer's disease research. Results: The simulation results indicate that the optimal AAUC combination performs well in the current study population. The optimal SAUC method is flexible to choose any reference populations, and allows the results to be generalized to different populations. Conclusions: The proposed optimal AAUC and SAUC approaches successfully address the covariate adjustment problem in estimating the optimal marker combination. The optimal SAUC method is preferred-for practical use, because the biomarker combination rule can be easily evaluated for different population of interest. C1 [Liu, Danping] NICHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Liu, DP (reprint author), NICHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM danping.liu@nih.gov FU National Institute of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); NIH/NIA [U01AG016976] FX D.L.'s research is supported by the Intramural Research Program of the National Institute of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). This work was supported in part by NIH/NIA grant U01AG016976. NR 16 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2013 VL 20 IS 7 BP 874 EP 882 DI 10.1016/j.acra.2013.03.009 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 168YT UT WOS:000320744600011 PM 23747153 ER PT J AU Riemenschneider, MJ Louis, DN Weller, M Hau, P AF Riemenschneider, Markus J. Louis, David N. Weller, Michael Hau, Peter TI Refined brain tumor diagnostics and stratified therapies: the requirement for a multidisciplinary approach SO ACTA NEUROPATHOLOGICA LA English DT Review DE Glioblastoma; Anaplastic glioma; Molecular diagnostics; BRAF; IDH1; MGMT; 1p/19q; Neuropathology; Neurooncology; Chemotherapy; Basic research; Translational research; Clinical research; Tissue banking ID RECURRENT GLIOBLASTOMA-MULTIFORME; HIGH-GRADE GLIOMAS; PHASE-II TRIAL; ENZASTAURIN PLUS TEMOZOLOMIDE; INTEGRATED GENOMIC ANALYSIS; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; ASPARTIC ACID PEPTIDE; CANCER STEM-CELL; MALIGNANT GLIOMAS AB Individualized therapies are popular current concepts in oncology and first steps towards stratified medicine have now been taken in neurooncology through implementation of stratified therapeutic approaches. Knowledge about the molecular basis of brain tumors has expanded greatly in recent years and a few molecular alterations are studied routinely because of their clinical relevance. However, no single targeted agent has yet been fully approved for the treatment of glial brain tumors. In this review, we argue that multidisciplinary and integrated approaches are essential for translational research and the development of new treatments for patients with malignant gliomas, and we present a conceptual framework in which to place the components of such an interdisciplinary approach. We believe that this ambitious goal can be best realized through strong cooperation of brain tumor centers with local hospitals and physicians; such an approach enables close dialogue between expert subspecialty clinicians and local therapists to consider all aspects of this increasingly complex set of diseases. C1 [Riemenschneider, Markus J.] Regensburg Univ Hosp, Dept Neuropathol, D-93053 Regensburg, Germany. [Riemenschneider, Markus J.; Hau, Peter] Regensburg Univ Hosp, Wilhelm Sander NeuroOncol Unit, D-93053 Regensburg, Germany. [Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Pathol Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Weller, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Hau, Peter] Univ Regensburg, Dept Neurol, D-93053 Regensburg, Germany. RP Riemenschneider, MJ (reprint author), Regensburg Univ Hosp, Dept Neuropathol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM Markus.Riemenschneider@ukr.de NR 148 TC 5 Z9 5 U1 1 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUL PY 2013 VL 126 IS 1 BP 21 EP 37 DI 10.1007/s00401-013-1127-4 PG 17 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 169LK UT WOS:000320781500002 PM 23689616 ER PT J AU Karlin, BE Walser, RD Yesavage, J Zhang, A Trockel, M Taylor, CB AF Karlin, Bradley E. Walser, Robyn D. Yesavage, Jerome Zhang, Aimee Trockel, Mickey Taylor, C. Barr TI Effectiveness of acceptance and commitment therapy for depression: Comparison among older and younger veterans SO AGING & MENTAL HEALTH LA English DT Article DE acceptance and commitment therapy; depression; older adults; geriatrics; veterans; effectiveness ID WORKING ALLIANCE INVENTORY; QUALITY-OF-LIFE; COGNITIVE-BEHAVIORAL THERAPY; CHRONIC PAIN PATIENTS; MENTAL-HEALTH-CARE; PSYCHOMETRIC PROPERTIES; STRESS REDUCTION; ADULTS; METAANALYSIS; MOOD AB Objectives: Limited data exist on outcomes of older adults receiving psychotherapy for depression in real-world settings. Acceptance and Commitment Therapy for depression (ACT-D) offers potential utility for older individuals who may experience issues of loss, reduced control, and other life changes. The present article examines and compares outcomes of older and younger Veterans receiving ACT-D nationally in the U.S. Department of Veterans Affairs health care system. Method: Patient outcomes were assessed using the Beck Depression Inventory-Second Edition and the World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed using the Working Alliance Inventory-Short Revised. Results: Six hundred fifty-five Veterans aged 18-64 and 76 Veterans aged 65+ received ACT-D. Seventy-eight percent of older and 67% of younger patients completed all sessions or finished early. Mean depression scores declined from 28.4 (SD = 11.4) to 17.5 (SD = 12.0) in the older group and 30.3 (SD = 10.6) to 19.1 (SD = 14.3) in the younger group. Within-group effect sizes were d = .95 and d = 1.06 for the two age groups, respectively. Quality of life and therapeutic alliance also increased during treatment. Conclusion: The findings suggest that ACT-D is an effective and acceptable treatment for older Veterans treated in routine clinical settings, including those with high levels of depression. C1 [Karlin, Bradley E.] Mental Hlth Serv, US Dept Vet Affairs, Cent Off, Washington, DC USA. [Karlin, Bradley E.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Walser, Robyn D.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Yesavage, Jerome; Zhang, Aimee; Trockel, Mickey; Taylor, C. Barr] Stanford Univ, Med Ctr, Dept Psychiat, Palo Alto, CA 94304 USA. [Yesavage, Jerome; Zhang, Aimee; Trockel, Mickey; Taylor, C. Barr] 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), Mental Hlth Serv, US Dept Vet Affairs, Cent Off, Washington, DC USA. EM bradley.karlin2@va.gov FU Mental Health Services, U.S. Department of Veterans Affairs Central Office FX This project was supported by Mental Health Services, U.S. Department of Veterans Affairs Central Office. NR 62 TC 12 Z9 13 U1 2 U2 28 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD JUL 1 PY 2013 VL 17 IS 5 BP 555 EP 563 DI 10.1080/13607863.2013.789002 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 171GN UT WOS:000320913300005 PM 23607328 ER PT J AU LaBuzetta, JN AF LaBuzetta, Jamie Nicole TI Moving Beyond Methylphenidate and Amphetamine: The Ethics of a Better "Smart Drug" SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID PUBLIC SPACES; DOUBLE-BLIND; MODAFINIL; VOLUNTEERS; PERFORMANCE; PLACEBO; SMOKING C1 [LaBuzetta, Jamie Nicole] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP LaBuzetta, JN (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM jlabuzetta@partners.org NR 11 TC 2 Z9 2 U1 1 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JUL 1 PY 2013 VL 13 IS 7 BP 43 EP 45 DI 10.1080/15265161.2013.794881 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 168GB UT WOS:000320692600014 PM 23767440 ER PT J AU Zhang, B Tian, M Zheng, H Zhen, Y Yue, Y Li, TZ Li, SR Marcantonio, ER Xie, ZC AF Zhang, Bin Tian, Ming Zheng, Hui Zhen, Yu Yue, Yun Li, Tianzuo Li, Shuren Marcantonio, Edward R. Xie, Zhongcong TI Effects of Anesthetic Isoflurane and Desflurane on Human Cerebrospinal Fluid A beta and tau Level SO ANESTHESIOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; AMYLOID-BETA; IN-VIVO; CASPASE ACTIVATION; COGNITIVE DECLINE; PROTEIN-LEVELS; APOPTOSIS; SURGERY; ARTERY; BIOMARKERS AB Background: Accumulation of -amyloid protein (A) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase A levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of A and tau in humans. Methods: The participants were assigned into spinal anesthesia (N = 35), spinal plus desflurane anesthesia (N = 33), or spinal plus isoflurane anesthesia (N = 38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of A (A40 and A42) and total tau in the CSF were determined. Results: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF A40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P = 0.022. Desflurane, but not isoflurane, was associated with a decrease in A42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P = 0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. Conclusions: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF A levels. C1 Beijing Friendship Hosp, Dept Anesthesia, Beijing, Peoples R China. Capital Med Univ, Beijing, Peoples R China. Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU Beijing science and technology development plan of the education committee; Keji Mian (KM) (Beijing, P.R. China) [200910025016]; National Science Foundation of China Oversea young scholar collaboration research award; National Science Foundation of China (NSF) (Beijing, P.R. China) [30928026]; National Institutes of Health, Bethesda, Maryland [R21AG029856, R21AG038994, R01 GM088801, K24AG035075]; Cure Alzheimer's Fund, Wellesley, Massachusetts FX Received from the Department of Anesthesia, Beijing Friendship Hospital and Capital Medical University, Beijing, China, and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Submitted for publication September 17, 2012. Accepted for publication January 30, 2013. This research was supported by Beijing science and technology development plan of the education committee, Keji Mian (KM) 200910025016 (Beijing, P.R. China) (to Ming Tian), CNational Science Foundation of China Oversea young scholar collaboration research award, National Science Foundation of China (NSF) 30928026 (Beijing, P.R. China) (to Zhongcong Xie and Yun Yue), R21AG029856, R21AG038994, and R01 GM088801 from the National Institutes of Health, Bethesda, Maryland; from Cure Alzheimer's Fund, Wellesley, Massachusetts (to Zhongcong Xie), and a Mid-Career Investigator Award (K24AG035075) from the National Institutes of Health, Bethesda, Maryland (to Edward R. Marcantonio). Part of this work was presented at the annual meeting of the American Society of Anesthesiologists, on October 16, 2010, in San Diego, California. Drs. Zhang and Tian contributed equally to this work. NR 46 TC 22 Z9 26 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2013 VL 119 IS 1 BP 52 EP 60 DI 10.1097/ALN.0b013e31828ce55d PG 9 WC Anesthesiology SC Anesthesiology GA 166TA UT WOS:000320579300015 PM 23438677 ER PT J AU Tucci, MR Costa, ELV Wellman, TJ Musch, G Winkler, T Harris, RS Venegas, JG Amato, MBP Melo, MFV AF Tucci, Mauro R. Costa, Eduardo L. V. Wellman, Tyler J. Musch, Guido Winkler, Tilo Harris, R. Scott Venegas, Jose G. Amato, Marcelo B. P. Melo, Marcos F. Vidal TI Regional Lung Derecruitment and Inflammation during 16 Hours of Mechanical Ventilation in Supine Healthy Sheep SO ANESTHESIOLOGY LA English DT Article ID FUNCTIONAL RESIDUAL CAPACITY; TIDAL VOLUME VENTILATION; GENERAL-ANESTHESIA; GAS-EXCHANGE; COMPUTED-TOMOGRAPHY; PULMONARY-FUNCTION; INJURY; ATELECTASIS; PET; MODEL AB Background: Lung derecruitment is common during general anesthesia. Mechanical ventilation with physiological tidal volumes could magnify derecruitment, and produce lung dysfunction and inflammation. The authors used positron emission tomography to study the process of derecruitment in normal lungs ventilated for 16 h and the corresponding changes in regional lung perfusion and inflammation. Methods: Six anesthetized supine sheep were ventilated with V-T = 8 ml/kg and positive end-expiratory pressure = 0. Transmission scans were performed at 2-h intervals to assess regional aeration. Emission scans were acquired at baseline and after 16 h for the following tracers: (1) F-18-fluorodeoxyglucose to evaluate lung inflammation and (2) (NN)-N-13 to calculate regional perfusion and shunt fraction. Results: Gas fraction decreased from baseline to 16 h in dorsal (0.31 +/- 0.13 to 0.14 +/- 0.12, P < 0.01), but not in ventral regions (0.61 +/- 0.03 to 0.63 +/- 0.07, P = nonsignificant), with time constants of 1.5-44.6 h. Although the vertical distribution of relative perfusion did not change from baseline to 16 h, shunt increased in dorsal regions (0.34 +/- 0.23 to 0.63 +/- 0.35, P < 0.01). The average pulmonary net F-18-fluorodeoxyglucose uptake rate in six regions of interest along the ventral-dorsal direction increased from 3.4 +/- 1.4 at baseline to 4.1 +/- 1.510(-3)/min after 16 h (P < 0.01), and the corresponding average regions of interest F-18-fluorodeoxyglucose phosphorylation rate increased from 2.0 +/- 0.2 to 2.5 +/- 0.210(-2)/min (P < 0.01). Conclusions: When normal lungs are mechanically ventilated without positive end-expiratory pressure, loss of aeration occurs continuously for several hours and is preferentially localized to dorsal regions. Progressive lung derecruitment was associated with increased regional shunt, implying an insufficient hypoxic pulmonary vasoconstriction. The increased pulmonary net uptake and phosphorylation rates of F-18-fluorodeoxyglucose suggest an incipient inflammation in these initially normal lungs. C1 [Tucci, Mauro R.; Costa, Eduardo L. V.; Wellman, Tyler J.; Musch, Guido; Winkler, Tilo; Harris, R. Scott; Venegas, Jose G.; Amato, Marcelo B. P.; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Institutes of Health, Bethesda, Maryland [5R01HL086827]; Coordination for the Improvement of Higher Level Personnel, Brasilia, Brazil; National Institutes of Health [R01HL094639] FX Supported by grant HL 5R01HL086827 from the National Institutes of Health, Bethesda, Maryland. Dr. Tucci received a scholarship from the Coordination for the Improvement of Higher Level Personnel, Brasilia, Brazil. Dr. Musch was supported by grant R01HL094639 from the National Institutes of Health. Presented at the Annual Meeting of the American Society of Anesthesiologists, New Orleans, Louisiana, October 17-21, 2009; abstract number A1379. NR 53 TC 5 Z9 6 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2013 VL 119 IS 1 BP 156 EP 165 DI 10.1097/ALN.0b013e31829083b8 PG 10 WC Anesthesiology SC Anesthesiology GA 166TA UT WOS:000320579300027 PM 23535501 ER PT J AU Pinciroli, R Mietto, C Berra, L AF Pinciroli, Riccardo Mietto, Cristina Berra, Lorenzo TI Use of High-definition Computed Tomography to Assess Endotracheal Tube Luminal Narrowing after Mechanical Ventilation SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Pinciroli, Riccardo; Mietto, Cristina; Berra, Lorenzo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Pinciroli, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. EM lberra@partners.org NR 3 TC 4 Z9 4 U1 1 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 JUL PY 2013 VL 119 IS 1 BP 202 EP 202 DI 10.1097/ALN.0b013e318291022d PG 1 WC Anesthesiology SC Anesthesiology GA 166TA UT WOS:000320579300033 PM 23535503 ER PT J AU Schnabel, RB Yin, XY Larson, MG Yamamoto, JF Fontes, JD Kathiresan, S Rong, J Levy, D Keaney, JF Wang, TJ Murabito, JM Vasan, RS Benjamin, EJ AF Schnabel, Renate B. Yin, Xiaoyan Larson, Martin G. Yamamoto, Jennifer F. Fontes, Joao D. Kathiresan, Sekar Rong, Jian Levy, Daniel Keaney, John F., Jr. Wang, Thomas J. Murabito, Joanne M. Vasan, Ramachandran S. Benjamin, Emelia J. TI Multiple Inflammatory Biomarkers in Relation to Cardiovascular Events and Mortality in the Community SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cardiovascular disease; cohort; epidemiology; inflammation; mortality ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; CORONARY-HEART-DISEASE; INTERCELLULAR-ADHESION MOLECULE-1; TYPE-2 DIABETIC-PATIENTS; RHEUMATOID-ARTHRITIS; BODY-COMPOSITION; RISK-FACTORS; OLDEST-OLD; MARKERS AB Objective Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. Approach and Results We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61 +/- 9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. Conclusions Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD. C1 [Schnabel, Renate B.; Yin, Xiaoyan; Larson, Martin G.; Yamamoto, Jennifer F.; Fontes, Joao D.; Rong, Jian; Levy, Daniel; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA USA. [Yin, Xiaoyan; Larson, Martin G.; Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Fontes, Joao D.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Kathiresan, Sekar] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. RP Schnabel, RB (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Bldg E 70 O70,Martinistr 52, D-20246 Hamburg, Germany. EM schnabelr@gmx.de RI Schnabel, Renate/F-6527-2014; OI Murabito, Joanne/0000-0002-0192-7516; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute [N01-/HC-/25195, 6R01-/NS17950]; NIH [HL064753, HL076784, AG028321, 1 RO1HL71039, K24 HL04334]; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-/1, SCHN 1149/3-/1]; Doris Duke Charitable Foundation Clinical Scientist Development Award [1K23HL083102] FX This work was supported by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute contract N01-/HC-/25195, 6R01-/NS17950, and NIH grants HL064753, HL076784, AG028321 (E.J. Benjamin), and 1 RO1HL71039 (R.S. Vasan); NIH Research career award K24 HL04334 (R.S. Vasan); Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-/1 and Emmy Noether Program SCHN 1149/3-/1 (R.B. Schnabel); 1K23HL083102, Doris Duke Charitable Foundation Clinical Scientist Development Award (S. Kathiresan). NR 49 TC 26 Z9 27 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2013 VL 33 IS 7 BP 1728 EP 1733 DI 10.1161/ATVBAHA.112.301174 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 167YP UT WOS:000320671800040 PM 23640499 ER PT J AU Perlis, RH AF Perlis, Roy H. TI A Clinical Risk Stratification Tool for Predicting Treatment Resistance in Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Antidepressant; depression; machine learning; prediction; risk stratification; selective serotonin reuptake inhibitor; treatment-resistant depression ID DIAGNOSTIC SCREENING QUESTIONNAIRE; ILLNESS RATING-SCALE; QUICK INVENTORY; BREAST-CANCER; SYMPTOMATOLOGY; REGRESSION; MODELS; VALIDATION; SELECTION; BURDEN AB Background: Early identification of depressed individuals at high risk for treatment resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Methods: Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by or readily amenable to self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacological treatment trial from those not reaching remission despite two trials. Results: A logistic regression model achieved an area under the receiver operating characteristic curve exceeding .71 in training, testing, and validation cohorts and maintained good calibration across cohorts. Performance of three alternative models with machine learning approaches-a naive Bayes classifier and a support vector machine, and a random forest model-was less consistent. Similar performance was observed between more and less severe depression, men and women, and primary versus specialty care sites. A web-based calculator was developed that implements this tool and provides graphical estimates of risk. Conclusion: Risk for treatment resistance among outpatients with major depressive disorder can be estimated with a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,6th Floor,Simches Res Bldg, Boston, MA 02114 USA. EM rperlis@partners.org FU National Institute of Mental Health [N01 MH-90003, MH086026]; Genomind; Healthrageous; Pamlab; Proteus Biomedical; RIDVentures FX The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study was supported by federal funds from the National Institute of Mental Health under contract N01 MH-90003 to the University of Texas-Southwestern Medical Center at Dallas (A.J. Rush, principal investigator). Dr. Perlis is supported by National Institute of Mental Health MH086026.; Dr. Perlis is a member of scientific advisory boards or has received consulting fees from Genomind, Healthrageous, Pamlab, Proteus Biomedical, and RIDVentures. He has received research support from Proteus Biomedical and royalties from Concordant Rater Systems (now UBC). NR 46 TC 31 Z9 32 U1 1 U2 19 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 JUL 1 PY 2013 VL 74 IS 1 BP 7 EP 14 DI 10.1016/j.biopsych.2012.12.007 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 166VM UT WOS:000320586900003 PM 23380715 ER PT J AU McCarthy, PL Hahn, T Hassebroek, A Bredeson, C Gajewski, J Hale, G Isola, L Lazarus, HM Lee, SJ LeMaistre, CF Loberiza, F Maziarz, RT Rizzo, JD Joffe, S Parsons, S Majhail, NS AF McCarthy, Philip L., Jr. Hahn, Theresa Hassebroek, Anna Bredeson, Christopher Gajewski, James Hale, Gregory Isola, Luis Lazarus, Hillard M. Lee, Stephanie J. LeMaistre, Charles F. Loberiza, Fausto Maziarz, Richard T. Rizzo, J. Douglas Joffe, Steven Parsons, Susan Majhail, Navneet S. TI Trends in Use of and Survival after Autologous Hematopoietic Cell Transplantation in North America, 1995-2005: Significant Improvement in Survival for Lymphoma and Myeloma during a Period of Increasing Recipient Age SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Autologous transplantation; Lymphoma; Myeloma; Survival; Treatment-related mortality ID MULTIPLE-MYELOMA; BREAST-CANCER; TRIAL; CHEMOTHERAPY; REGIMENS; ERA AB Autologous hematopoietic cell transplantation (auto-HCT) is performed to treat relapsed and recurrent malignant disorders and as part of initial therapy for selected malignancies. This study evaluated changes in use, techniques, and survival in a population-based cohort of 68,404 patients who underwent first auto-HCT in a US or Canadian center between 1994 and 2005 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The mean annual number of auto-HCTs performed was highest during 1996-1999 (6948), and decreased subsequently 2000-2003 (4783), owing mainly to fewer auto-HCTs done to treat breast cancer. However, the mean annual number of auto-HCTs increased from 5278 annually in 1994-1995 to 5459 annually in 2004-2005, reflecting increased use for multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Despite an increase in the median recipient age from 44 to 53 years, there has been a significant improvement in overall survival (OS) from 1994 to 2005 in patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma (day +100 OS, from 85% to 96%; 1-year OS, from 68% to 80%; P < .001) and chemotherapy-sensitive multiple myeloma (day +100 OS, from 96% to 98%; 1-year OS, from 83% to 92%; P < .001). This improvement in OS was most pronounced in middle-aged (>40 years) and older (>60 years) individuals. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [McCarthy, Philip L., Jr.; Hahn, Theresa] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Hassebroek, Anna; Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Bredeson, Christopher] Ottawa Hosp, Blood & Marrow Transplant Program, Div Hematol, Ottawa, ON, Canada. [Gajewski, James; Maziarz, Richard T.] Oregon Hlth & Sci Univ, Bone Marrow Transplant Program, Portland, OR 97201 USA. [Hale, Gregory] Univ S Florida, All Childrens Hosp, Hematol Oncol BMT Program, St Petersburg, FL 33701 USA. [Isola, Luis] Mt Sinai Med Ctr, Bone Marrow Transplant Program, New York, NY 10029 USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Univ Comprehens Canc Ctr, Dept Med, Cleveland, OH 44106 USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Clin Transplant Res Div, Seattle, WA 98104 USA. [LeMaistre, Charles F.] Sarah Cannon, Nashville, TN USA. [Loberiza, Fausto] Univ Nebraska Med Ctr, Div Hematol Oncol, Omaha, NE USA. [Rizzo, J. Douglas] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Boston, MA 02115 USA. [Parsons, Susan] Tufts Med Ctr, Hlth Inst, Boston, MA USA. [Majhail, Navneet S.] Natl Marrow Donor Program, Minneapolis, MN 55413 USA. RP Majhail, NS (reprint author), Natl Marrow Donor Program, 3001 Broadway Ave NE,Suite 100, Minneapolis, MN 55413 USA. EM nmajhail@nmdp.org OI Joffe, Steven/0000-0002-0667-7384 FU Public Health Service Grant/Cooperative Agreement, National Cancer Institute [U24-CA76518]; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Cancer Institute [5U01HL069294]; Health Resources and Services Administration [HHSH234200637015 C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos; Amgen; Angioblast FX This study had no specific funding or grant support. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, National Heart, Lung and Blood Institute, and National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U01HL069294 from the National Cancer Institute and National Heart, Lung and Blood Institute; Contract HHSH234200637015 C with the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Amgen, Angioblast, anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association, Buchanan Family Foundation, CaridianBCT, Celgene, CellGenix, Children's Leukemia Research Association, Fresenius-Biotech North America, Gamida Cell Teva Joint Venture, Genentech, Genzyme, GlaxoSmithKline, Histo-Genetics, Kiadis Pharma, Leukemia & Lymphoma Society, Medical College of Wisconsin, Merck & Co, Millennium: Takeda Oncology, Milliman USA, Miltenyi Biotec, National Marrow Donor Program, Optum Healthcare Solutions, Osiris Therapeutics, Otsuka America Pharmaceutical, RemedyMD, Sanofi, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, StemCyte, Stemsoft Software, Swedish Orphan Biovitrum, Tarix Pharmaceuticals, Teva Neuroscience, Therakos, and Wellpoint. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US government. NR 13 TC 46 Z9 47 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2013 VL 19 IS 7 BP 1116 EP 1123 DI 10.1016/j.bbmt.2013.04.027 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 173QH UT WOS:000321093500019 PM 23660172 ER PT J AU Munshi, NC Anderson, KC AF Munshi, Nikhil C. Anderson, Kenneth C. TI New Strategies in the Treatment of Multiple Myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; POTENTIAL THERAPEUTIC APPLICATION; HISTONE DEACETYLASE INHIBITION; BONE-MARROW MICROENVIRONMENT; SINGLE-AGENT CARFILZOMIB; CELL-ACTIVATING FACTOR; LOW-DOSE DEXAMETHASONE; IMMUNOMODULATORY DRUGS; IN-VIVO; PRECLINICAL MODELS AB Multiple myeloma is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation have improved survival in younger patients, the natural history of multiple myeloma has been changed with the availability of six new agents approved in the past 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin, carfilzomib, and pomalidomide). Despite this significant improvement in the overall outcome, multiple myeloma remains incurable in the majority of patients, prompting a continued search for additional therapeutic options. Extensive molecular and genomic characterization of multiple myeloma cells in their bone marrow milieu, which affects myeloma cell growth and survival, has provided a number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in multiple myeloma. Similarly, improvements in monoclonal antibody generation and vaccine development, along with identification of a number of cell surface and cellular targets, have led to the development of various strategies, including antibodies and antibody-drug conjugates that are under investigation preclinically and in early clinical studies. We propose that eventually, molecularly informed multiagent combination therapies will be required to eliminate the multiple myeloma cell clone for long-term disease control. (C)2013 AACR. C1 [Munshi, Nikhil C.] Vet Adm Boston Healthcare Syst, Boston, MA USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,M230, Boston, MA 02215 USA. EM Nikhil_Munshi@DFCI.Harvard.edu FU Veterans Administration [I01-BX001584]; NIH [RO1-124929, P50-100007, PO1-78378, PO1-155258, RO1-50947] FX This work was supported in part by grants from the Veterans Administration I01-BX001584 and NIH grant RO1-124929 (to N.C. Munshi); NIH Grants P50-100007, PO1-78378, and PO1-155258 (to N.C. Munshi and K. C. Anderson); and NIH Grant RO1-50947 (to K. C. Anderson). NR 71 TC 46 Z9 50 U1 0 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2013 VL 19 IS 13 BP 3337 EP 3344 DI 10.1158/1078-0432.CCR-12-1881 PG 8 WC Oncology SC Oncology GA 173RF UT WOS:000321095900003 PM 23515406 ER PT J AU Chen, BJ Chapuy, B Jing, OY Sun, HH Roemer, MGM Xu, ML Yu, HB Fletcher, CDM Freeman, GJ Shipp, MA Rodig, SJ AF Chen, Benjamin J. Chapuy, Bjoern Jing Ouyang Sun, Heather H. Roemer, Margaretha G. M. Xu, Mina L. Yu, Hongbo Fletcher, Christopher D. M. Freeman, Gordon J. Shipp, Margaret A. Rodig, Scott J. TI PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID EPSTEIN-BARR-VIRUS; CLASSICAL HODGKIN LYMPHOMA; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; TUMOR-ASSOCIATED MACROPHAGES; PROTEIN EXPRESSION; DISTINCT ENTITY; STERNBERG CELLS; IMMUNITY; B7-H1; EBV AB Purpose: Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed-Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus-and immunodeficiency-associated tumors. Experimental Design: Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1. Results: Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1. Conclusion: Certain aggressive B-cell lymphomas and virus-and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies. (C)2013 AACR. C1 [Chen, Benjamin J.; Sun, Heather H.; Fletcher, Christopher D. M.; Rodig, Scott J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Cambridge, MA 02138 USA. [Chapuy, Bjoern; Jing Ouyang; Roemer, Margaretha G. M.; Freeman, Gordon J.; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yu, Hongbo] Univ Massachusetts, Sch Med, Dept Pathol, UMass Mem Med Ctr, Worcester, MA 01605 USA. [Xu, Mina L.] Yale Sch Med, New Haven, CT USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Amory 3rd Floor,75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org FU Specialized Center of Research (SCOR) grant from the Leukemia and Lymphoma Society; NIH [AI56299, AI080192, U54CA163125]; [R01 CA161026] FX This work was financially supported, in part, by R01 CA161026 (to M. A. Shipp), a Specialized Center of Research (SCOR) grant from the Leukemia and Lymphoma Society (to M. A. Shipp and S.J. Rodig), and NIH grants AI56299, AI080192, and U54CA163125 (to G.J. Freeman). NR 36 TC 180 Z9 186 U1 4 U2 23 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 JUL 1 PY 2013 VL 19 IS 13 BP 3462 EP 3473 DI 10.1158/1078-0432.CCR-13-0855 PG 12 WC Oncology SC Oncology GA 173RF UT WOS:000321095900015 PM 23674495 ER PT J AU Shibata, SI Chung, V Synold, TW Longmate, JA Suttle, AB Ottesen, LH Lenz, HJ Kummar, S Harvey, RD Hamilton, AL O'Neil, BH Lenz, HJ Kummar, S Harvey, RD Hamilton, AL O'Neil, BH Sarantopoulos, J LoRusso, P Rudek, MA Dowlati, A Mulkerin, DL Belani, CP Gandhi, L Lau, SC Ivy, SP Newman, EM AF Shibata, Stephen I. Chung, Vincent Synold, Timothy W. Longmate, Jeffrey A. Suttle, A. Benjamin Ottesen, Lone H. Lenz, Heinz-Josef Kummar, Shivaani Harvey, R. Donald Hamilton, Anne L. O'Neil, Bert H. Lenz, Heinz-Josef Kummar, Shivaani Harvey, R. Donald Hamilton, Anne L. O'Neil, Bert H. Sarantopoulos, John LoRusso, Patricia Rudek, Michelle A. Dowlati, Afshin Mulkerin, Daniel L. Belani, Chandra P. Gandhi, Leena Lau, S. Cecilia Ivy, S. Percy Newman, Edward M. TI Phase I Study of Pazopanib in Patients with Advanced Solid Tumors and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study SO CLINICAL CANCER RESEARCH LA English DT Article ID ORAL PAZOPANIB; INHIBITOR; TRIAL AB Purpose: Pazopanib is a potent, multitargeted receptor tyrosine kinase inhibitor; however, there is limited information regarding the effects of liver function on pazopanib metabolism and pharmacokinetics. The objective of this study was to establish the maximum-tolerated dose (MTD) and pharmacokinetic profile of pazopanib in patients with varying degrees of hepatic dysfunction. Experimental Design: Patients with any solid tumors or lymphoma were stratified into four groups based on the degree of hepatic dysfunction according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. Pazopanib was given orally once a day on a 21-day cycle. A modified 3+3 design was used. Results: Ninety-eight patients were enrolled. Patients in the mild group tolerated 800 mg per day. The moderate and severe groups tolerated 200 mg per day. Pharmacokinetic data in the mild group were similar to the data in the normal group. Comparison of the median C-max and area under the curve [AUC((0-24))] in the moderate or severe groups at 200 mg per day to the values in the normal and mild groups at 800 mg per day indicated less than dose-proportional systemic exposures in patients with moderate and severe hepatic impairment. This suggests that the lower maximum-tolerated dose in the moderate and severe group is not due to a decrease in drug clearance or alteration in the proportion of metabolites. Conclusions: In patients with mild liver dysfunction, pazopanib is well tolerated at the Food and Drug Administration (FDA)-approved dose of 800 mg per day. Patients with moderate and severe liver dysfunction tolerated 200 mg per day. Clin Cancer Res; 19(13); 3631-9. (C)2013 AACR. C1 [Shibata, Stephen I.; Chung, Vincent; Synold, Timothy W.; Longmate, Jeffrey A.; Lau, S. Cecilia; Newman, Edward M.] City Hope Natl Med Ctr, Duarte, CA USA. [Lenz, Heinz-Josef] Univ So Calif, Los Angeles, CA USA. [Kummar, Shivaani] Natl Canc Inst, Bethesda, MD 20892 USA. [Ivy, S. Percy] Natl Canc Inst, Bethesda, MD USA. [Ivy, S. Percy] NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Rudek, Michelle A.] Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Harvey, R. Donald] Emory Univ, Sch Med, Atlanta, GA USA. [O'Neil, Bert H.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Sarantopoulos, John] Inst Drug Dev CTRC, San Antonio, TX USA. [LoRusso, Patricia] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Mulkerin, Daniel L.] Univ Wisconsin, Madison, WI USA. [Belani, Chandra P.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hamilton, Anne L.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. RP Newman, EM (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, North,Room 2000A,1500 East Duarte Rd, Duarte, CA 91010 USA. EM enewman@coh.org OI Belani, Chandra/0000-0001-5049-5329; Gandhi, Leena/0000-0002-2398-9179 FU NIH [U01-CA062505, P30-CA033572, U01-CA062487, U01-CA099168, U01-CA70095, P30-CA006973, U01-CA069853, P30-CA054174, U01-CA062490, U01-CA062502, U01-C 062491] FX The study was supported by NIH grants: U01-CA062505 and P30-CA033572 (Beckman Research Institute of City of Hope, Duarte, CA); U01-CA062487 (Karmanos Cancer Institute, Detroit, MI); U01-CA099168 (University of Pittsburgh, Pittsburgh, PA); U01-CA70095 and P30-CA006973 (Johns Hopkins University, Baltimore, MD); U01-CA069853 and P30-CA054174 (Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX); U01-CA062490 (Dana-Farber Cancer Institute, Boston, MA); U01-CA062502 (Case Western Reserve, Cleveland, OH); and U01-C 062491 (University of Wisconsin Paul P Carbone Comprehensive Cancer Center, Madison, WI). NR 10 TC 15 Z9 15 U1 1 U2 5 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 JUL 1 PY 2013 VL 19 IS 13 BP 3631 EP 3639 DI 10.1158/1078-0432.CCR-12-3214 PG 9 WC Oncology SC Oncology GA 173RF UT WOS:000321095900030 PM 23653147 ER PT J AU Rosenblatt, J Avivi, I Vasir, B Uhl, L Munshi, NC Katz, T Dey, BR Somaiya, P Mills, H Campigotto, F Weller, E Joyce, R Levine, JD Tzachanis, D Richardson, P Laubach, J Raje, N Boussiotis, V Yuan, YE Bisharat, L Held, V Rowe, J Anderson, K Kufe, D Avigan, D AF Rosenblatt, Jacalyn Avivi, Irit Vasir, Baldev Uhl, Lynne Munshi, Nikhil C. Katz, Tami Dey, Bimalangshu R. Somaiya, Poorvi Mills, Heidi Campigotto, Federico Weller, Edie Joyce, Robin Levine, James D. Tzachanis, Dimitrios Richardson, Paul Laubach, Jacob Raje, Noopur Boussiotis, Vassiliki Yuan, Yan Emily Bisharat, Lina Held, Viki Rowe, Jacob Anderson, Kenneth Kufe, Donald Avigan, David TI Vaccination with Dendritic Cell/Tumor Fusions following Autologous Stem Cell Transplant Induces Immunologic and Clinical Responses in Multiple Myeloma Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; ALLOGENEIC BONE-MARROW; CARCINOMA-CELLS; EUROPEAN GROUP; IMMUNIZATION; ANTIGENS; BREAST; IMMUNOTHERAPY; TOLERANCE; HYBRIDS AB Purpose: A multiple myeloma vaccine has been developed whereby patient-derived tumor cells are fused with autologous dendritic cells, creating a hybridoma that stimulates a broad antitumor response. We report on the results of a phase II trial in which patients underwent vaccination following autologous stem cell transplantation (ASCT) to target minimal residual disease. Experimental Design: Twenty-four patients received serial vaccinations with dendritic cell/myeloma fusion cells following posttransplant hematopoietic recovery. A second cohort of 12 patients received a pretransplant vaccine followed by posttransplant vaccinations. Dendritic cells generated from adherent mononuclear cells cultured with granulocyte macrophage colony-stimulating factor, interleukin-4, and TNF-alpha were fused with autologous bone marrow-derived myeloma fusion cells using polyethylene glycol. Fusion cells were quantified by determining the percentage of cells that coexpress dendritic cell and myeloma fusion antigens. Results: The posttransplant period was associated with reduction in general measures of cellular immunity; however, an increase in CD4 and CD8(+) myeloma-specific T cells was observed after ASCT that was significantly expanded following posttransplant vaccination. Seventy-eight percent of patients achieved a best response of complete response (CR)+very good partial response (VGPR) and 47% achieved a CR/near CR (nCR). Remarkably, 24% of patients who achieved a partial response following transplant were converted to CR/nCR after vaccination and at more than 3 months posttransplant, consistent with a vaccine-mediated effect on residual disease. Conclusions: The posttransplant period for patients with multiple myeloma provides a unique platform for cellular immunotherapy in which vaccination with dendritic cell/myeloma fusion fusions resulted in the marked expansion of myeloma-specific T cells and cytoreduction of minimal residual disease. Clin Cancer Res; 19(13); 3640-8. (C)2013 AACR. C1 [Rosenblatt, Jacalyn; Uhl, Lynne; Somaiya, Poorvi; Mills, Heidi; Joyce, Robin; Levine, James D.; Tzachanis, Dimitrios; Boussiotis, Vassiliki; Yuan, Yan Emily; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, Baldev; Munshi, Nikhil C.; Campigotto, Federico; Weller, Edie; Richardson, Paul; Laubach, Jacob; Anderson, Kenneth; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dey, Bimalangshu R.; Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Avivi, Irit; Katz, Tami; Bisharat, Lina; Held, Viki; Rowe, Jacob] Rambam Med Ctr, Haifa, Israel. RP Rosenblatt, J (reprint author), Beth Israel Deaconess Med Ctr, East Campus,KS-121,330 Brookline Ave, Boston, MA 02215 USA. EM jrosenb1@bidmc.harvard.edu FU Leukemia and Lymphoma Society (LLS) [R6133-05]; Multiple Myeloma Research Foundation (MMRF); National Institute of Health (NIH) [5 PO1 CA078378-10] FX This work was funded in part by the Leukemia and Lymphoma Society (LLS grant no. R6133-05 to D. E. Avigan), the Multiple Myeloma Research Foundation (MMRF Senior Research Award to D. E. Avigan), and the National Institute of Health (NIH grant no. 5 PO1 CA078378-10 to K. C. Anderson). K. C. Anderson is an American Cancer Society Clinical Research Professor. Dr. G. Dranoff critically reviewed the article. NR 29 TC 54 Z9 54 U1 1 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2013 VL 19 IS 13 BP 3640 EP 3648 DI 10.1158/1078-0432.CCR-13-0282 PG 9 WC Oncology SC Oncology GA 173RF UT WOS:000321095900031 PM 23685836 ER PT J AU Sessa, C Shapiro, GI Bhalla, KN Britten, C Jacks, KS Mita, M Papadimitrakopoulou, V Pluard, T Samuel, TA Akimov, M Quadt, C Fernandez-Ibarra, C Lu, H Bailey, S Chica, S Banerji, U AF Sessa, Cristiana Shapiro, Geoffrey I. Bhalla, Kapil N. Britten, Carolyn Jacks, Karen S. Mita, Monica Papadimitrakopoulou, Vali Pluard, Tim Samuel, Thomas A. Akimov, Mikhail Quadt, Cornelia Fernandez-Ibarra, Cristina Lu, Hong Bailey, Stuart Chica, Sandra Banerji, Udai TI First-in-Human Phase I Dose-Escalation Study of the HSP90 Inhibitor AUY922 in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID SHOCK-PROTEIN 90; BREAST-CANCER; CHAPERONE INHIBITORS; CLINICAL DEVELOPMENT; MOLECULAR CHAPERONE; TANESPIMYCIN 17-AAG; DRUG DEVELOPMENT; TRASTUZUMAB; NVP-AUY922; FUTURE AB Purpose: A phase I study was conducted with the primary objective of determining the maximum tolerated dose (MTD) of AUY922 in patients with advanced solid tumors. Secondary objectives included characterization of the safety, pharmacokinetic, and pharmacodynamic profiles. Patients and Methods: Patients with advanced solid tumors received 1-hour i.v. infusions of AUY922 once a week in a 28-day cycle. An adaptive Bayesian logistic regression model that employed observed dose-limiting toxicities (DLT) in the first treatment cycle was used to guide dose-escalation decisions, with the established MTD to be used in phase II studies. Results: One hundred and one patients were enrolled and explored at doses in the range of 2 to 70mg/m(2). DLTs occurred in 8 patients (22-70 mg/m(2)) and included diarrhea, asthenia/fatigue, anorexia, atrial flutter, and visual symptoms. At 70 mg/m(2), the AUY922 concentration achieved was consistent with active concentrations in a range of xenograft models. There was evidence of target inhibition in peripheral blood mononuclear cells (HSP70 induction) and tumor (client protein depletion and reduction of metabolic activity by F-18-FDG PET). The recommended phase II dose (RP2D) of 70mg/m(2) was proposed on the basis of toxicity and pharmacokinetic and pharmacodynamic profiles. Conclusions: At the RP2D of 70 mg/m(2), AUY922 exhibited acceptable tolerability, and phase II single-agent and combination studies have been initiated in patients with HER2-positive breast, gastric, and non-small cell lung cancers. Clin Cancer Res; 19(13); 3671-80. (C)2013 AACR. C1 [Banerji, Udai] Inst Canc Res, Drug Dev Unit, Sutton, Surrey, England. [Akimov, Mikhail; Quadt, Cornelia; Fernandez-Ibarra, Cristina; Bailey, Stuart] Novartis Pharma AG, Basel, Switzerland. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Bhalla, Kapil N.] Univ Kansas Canc Ctr, Kansas City, KS USA. [Britten, Carolyn] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Britten, Carolyn] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Jacks, Karen S.] Nevada Canc Inst, Las Vegas, NV USA. [Mita, Monica] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. [Papadimitrakopoulou, Vali] MD Anderson Canc Ctr, Houston, TX USA. [Pluard, Tim] Washington Univ, St Louis, MO USA. [Samuel, Thomas A.] Georgia Hlth Sci Univ, Augusta, GA USA. [Lu, Hong; Chica, Sandra] Novartis Pharmaceut, E Hanover, NJ USA. [Banerji, Udai] Royal Marsden NHS Fdn Trust, Inst Canc Res, Drug Dev Unit, Sutton SM2 5PT, Surrey, England. [Banerji, Udai] Royal Marsden Hosp, Sutton, Surrey, England. RP Banerji, U (reprint author), Royal Marsden NHS Fdn Trust, Inst Canc Res, Drug Dev Unit, Sycamore House,Downs Rd, Sutton SM2 5PT, Surrey, England. EM udai.banerji@icr.ac.uk OI Banerji, Udai/0000-0003-1503-3123 FU Novartis Pharmaceuticals; Cancer Research UK; ECMC; NIHR Biomedical Research Centre FX The authors thank the participating patients, their families, all study co-investigators, and research coordinators. Medical editorial assistance was provided by Matthew Naylor, PhD, and was funded by Novartis Pharmaceuticals. The Drug Development Unit at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust acknowledge infrastructural funding from Cancer Research UK, ECMC, and NIHR Biomedical Research Centre for Cancer grants. NR 39 TC 63 Z9 63 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 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2013 VL 19 IS 13 BP 3671 EP 3680 DI 10.1158/1078-0432.CCR-12-3404 PG 10 WC Oncology SC Oncology GA 173RF UT WOS:000321095900034 PM 23757357 ER PT J AU VanKirk, KK Horner, MD Turner, TH Dismuke, CE Muzzy, W AF VanKirk, Kathryn K. Horner, Michael David Turner, Travis H. Dismuke, Clara E. Muzzy, Wendy TI CE Hospital Service Utilization is Reduced Following Neuropsychological Evaluation in a Sample of US Veterans SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Health care utilization; Neuropsychological assessment; Clinical neuropsychology; Health outcomes; Cost-effectiveness ID COGNITIVE REHABILITATION; CLINICAL NEUROPSYCHOLOGY; HEALTH; ALZHEIMERS; OUTCOMES; UTILITY; COST AB The aim of this study was to evaluate the objective value of neuropsychological evaluation (NPE) through reduction in Emergency Room (ER) visits and hospitalizations. Retrospective analysis examined trends in ER visits and hospitalizations in 440 U.S. veterans who completed NPE between the years of 2003 and 2010. Within-subjects comparisons showed significant decreases in incidence of hospitalization and length of hospitalization in the year after evaluation compared to the year prior. Mean number of hospitalizations declined from 0.31 (SD = 0.64) pre-NPE to 0.22 (SD = 0.59) post-NPE; there were a total of 41 fewer hospitalizations in the year following NPE. Mean length of hospitalization decreased from 1.9 days (SD = 5.6) pre-NPE to 1.06 days (SD = 3.9) post-NPE; there were a total of 368 fewer days of hospitalization post-NPE. This reduction was not attributable to age or time. Incidence of ER visits also decreased from pre-NPE (M = 0.74, SD = 1.3) to post-evaluation (M = 0.69, SD = 1.3), though this was not significant. These findings provide preliminary evidence of the clinical and potential economic value of neuropsychological services within a medical setting. Follow-up studies should examine individual and exam-specific factors that may contribute to reduced utilization. C1 [VanKirk, Kathryn K.; Horner, Michael David; Turner, Travis H.] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [VanKirk, Kathryn K.; Horner, Michael David; Turner, Travis H.; Muzzy, Wendy] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Turner, Travis H.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Dismuke, Clara E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. [Dismuke, Clara E.] Med Univ S Carolina, Dept Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Muzzy, Wendy] Charleston Res Inst, Charleston, SC USA. RP VanKirk, KK (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. NR 26 TC 4 Z9 4 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD JUL 1 PY 2013 VL 27 IS 5 BP 750 EP 761 DI 10.1080/13854046.2013.783122 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 170OR UT WOS:000320863200001 PM 23548168 ER PT J AU Kohn, R Harhay, MO Cooney, E Small, DS Halpern, SD AF Kohn, Rachel Harhay, Michael O. Cooney, Elizabeth Small, Dylan S. Halpern, Scott D. TI Do Windows or Natural Views Affect Outcomes or Costs Among Patients in ICUs? SO CRITICAL CARE MEDICINE LA English DT Article DE environmental interventions; healthcare costs; ICU outcomes; windows ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; HOSPITAL MORTALITY; DELIRIUM; DESIGN; LENGTH; IDENTIFICATION; GUIDELINES; SURGERY; LIGHT AB Objective: To determine whether potential exposure to natural light via windows or to more pleasing views through windows affects outcomes or costs among critically ill patients. Design: Retrospective cohort study. Setting: An academic hospital in Philadelphia, PA. Patients: Six thousand one hundred thirty-eight patients admitted to a 24-bed medical ICU and 6,631 patients admitted to a 24-bed surgical ICU from July 1, 2006, to June 30, 2010. Interventions: Assignment to medical ICU rooms with vs. without windows and to surgical ICU rooms with natural vs. industrial views based on bed availability. Measurements and Main Results: In primary analyses adjusting for patient characteristics, medical ICU patients admitted to rooms with (n = 4,093) versus without (n = 2,243) windows did not differ in rates of ICU (p = 0.25) or in-hospital (p = 0.94) mortality, ICU readmissions (p = 0.37), or delirium (p = 0.56). Surgical ICU patients admitted to rooms with natural (n = 3,072) versus industrial (n = 3,588) views experienced slightly shorter ICU lengths of stay and slightly lower variable costs. Instrumental variable analyses based on initial bed assignment and exposure time did not show any differences in any outcomes in either the medical ICU or surgical ICU cohorts, and none of the differences noted in primary analyses remained statistically significant when adjusting for multiple comparisons. In a prespecified subgroup analysis among patients with ICU length of stay greater than 72 hours, MICU windows were associated with reduced ICU (p = 0.02) and hospital mortality (p = 0.04); these results did not meet criteria for significance after adjustment for multiple comparisons. Conclusions: ICU rooms with windows or natural views do not improve outcomes or reduce costs of in-hospital care for general populations of medical and surgical ICU patients. Future work is needed to determine whether targeting light from windows directly toward patients influences outcomes and to explore these effects in patients at high risk for adverse outcomes. C1 [Kohn, Rachel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Harhay, Michael O.; Cooney, Elizabeth; Halpern, Scott D.] Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. [Harhay, Michael O.; Cooney, Elizabeth; Halpern, Scott D.] Univ Penn, Fostering Improvement End Life Decis Sci FIELDS P, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Dept Med, Div Pulmonol Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Halpern, SD (reprint author), Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. EM shalpern@exchange.upenn.edu OI Harhay, Michael/0000-0002-0553-674X FU Agency for Healthcare Research and Quality [K08 HS018406]; National Institute of Aging; Greenwall Foundation; Otta Haas Charitable Trust; University of Michigan; University of Pennsylvania Center for Excellence in Cancer Communication Res; NIH; Agency for Healthcare Research and Quality FX Dr. Halpern was supported by K08 HS018406 from the Agency for Healthcare Research and Quality. This sponsor had no role in the design or conduct of the study, in the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript. Dr. Halpern has grants pending with the National Institute of Aging, Greenwall Foundation, Otta Haas Charitable Trust, University of Michigan, and University of Pennsylvania Center for Excellence in Cancer Communication Res, funding from NIH. Dr. Kohn received funding from the Agency for Healthcare Research and Quality. The remaining authors have not disclosed any potential conflicts of interest. NR 28 TC 5 Z9 5 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2013 VL 41 IS 7 BP 1645 EP 1655 DI 10.1097/CCM.0b013e318287f6cb PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 166TE UT WOS:000320579800026 PM 23535589 ER PT J AU Bronshteyn, YS Alston, TA AF Bronshteyn, Yuriy S. Alston, Theodore A. TI Help for the Miffed Heart SO CRITICAL CARE MEDICINE LA English DT Article DE cardiomyopathy; colchicine; inflammation; macrophage migration inhibitory factor; microtubule ID MIGRATION-INHIBITORY FACTOR; SEPSIS; DYSFUNCTION; BINDING; TUBULIN C1 Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia, Crit Care & Pain Med, Boston, MA USA. [Bronshteyn, Yuriy S.; Alston, Theodore A.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Bronshteyn, YS (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. OI Bronshteyn, Yuriy/0000-0002-9250-9490 NR 15 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2013 VL 41 IS 7 BP 1829 EP 1830 DI 10.1097/CCM.0b013e31828c252a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 166TE UT WOS:000320579800061 PM 23774356 ER PT J AU Sonpavde, G Je, YJ Schutz, F Galsky, MD Paluri, R Rosenberg, JE Bellmunt, J Choueiri, TK AF Sonpavde, Guru Je, Youjin Schutz, Fabio Galsky, Matthew D. Paluri, Ravikumar Rosenberg, Jonathan E. Bellmunt, Joaquim Choueiri, Toni K. TI Venous thromboembolic events with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A systematic review and meta-analysis of randomized clinical trials SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Vascular endothelial growth factor receptor; Tyrosine kinase inhibitors; Approved; Venous thromboembolic events; Meta-analysis ID CELL LUNG-CANCER; PHASE-II; DOUBLE-BLIND; 2ND-LINE TREATMENT; INTERFERON-ALPHA; PLUS DOCETAXEL; BEVACIZUMAB; PLACEBO; VANDETANIB; RISK AB A trial-level meta-analysis was conducted to determine the relative risk (RR) of venous thromboembolic events (VTEs) associated with approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TIC]). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without a Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, vandetanib, and axitinib). Statistical analyses calculated the RR and 95% confidence intervals (CI), using random-effects or fixed-effects models based on heterogeneity. A total of 7441 patients from 9 phase III trials and 8 phase II trials were selected. The RR of all grade and high-grade VTEs for the TKI vs. no TKI arms was 1.10 (95% CI 0.73-1.66, p = 0.64) and 0.85 (95% CI: 0.58-1.25, p = 0.41), respectively. No difference in risk was found based on tumor type, age and trial design. The majority of trials exhibited high quality per Jadad scoring and no heterogeneity or publication bias was found. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Sonpavde, Guru; Paluri, Ravikumar] Univ Alabama Birmingham, Dept Med, Sect Med Oncol, Birmingham, AL 35294 USA. [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Schutz, Fabio] Sao Jose Hosp, Dept Med Oncol, Sao Paulo, Brazil. [Galsky, Matthew D.] Mt Sinai Tisch Canc Inst, Sect Med Oncol, Dept Med, New York, NY USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bellmunt, Joaquim] Univ Hosp Del Mar IMIM, Dept Med Oncol, Barcelona, Spain. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Kidney Canc Ctr, 44 Binney St Dana 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu OI Rosenberg, Jonathan/0000-0003-2637-4249; paluri, ravi/0000-0002-2317-7082 FU Trust Family Research Fund for Kidney Cancer; Novartis; Pfizer; Speaker or Advisory board for Pfizer; GSK; Celgene; Dendreon; Viatar; Advisory board for Bayer/Onyx Pharmaceuticals; Abbot; Genentech; Aveo; Agennix; GlaxoSmithKline FX This study was funded by the philanthropic Trust Family Research Fund for Kidney Cancer. The funding source did not have any role in this study. The authors had access to all raw data and had the final responsibility for the decision to submit the manuscript for publication.; GS received from research support from Novartis, Pfizer; Speaker or Advisory board for Pfizer, Novartis, GSK. MDG received from research funding: Celgene, Dendreon, Novartis, Viatar; Advisory board: GSK, Amgen, BMS, Pfizer. JER received from Research support from Novartis, GSK. JB received from research support from Advisory board: Pfizer, GSK, Novartis, Aveo, Bayer/Onyx. TKC received from research support from Advisory board for Bayer/Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Abbot, Genentech, Aveo, and Agennix. No speaker's bureau. FABS, Paluri. YJ have not received any financial support. NR 43 TC 22 Z9 22 U1 0 U2 9 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 JUL PY 2013 VL 87 IS 1 BP 80 EP 89 DI 10.1016/j.critrevonc.2012.12.006 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 169BC UT WOS:000320750900007 PM 23317774 ER PT J AU Karaosmanoglu, AD Butros, SR Arellano, R AF Karaosmanoglu, Ali Devrim Butros, Selim R. Arellano, Ronald TI Imaging findings of renal toxicity in patients on chronic lithium therapy SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article ID NEPHROPATHY AB Lithium salts are the mainstay of treatment of bipolar disorder. However, the therapeutic index of lithium is narrow, and severe side effects may be seen. Nephrotoxicity is the most important side effect, which may progress to chronic renal failure. In this pictorial essay, we present ultrasonography, computed tomography, and magnetic resonance imaging findings of renal toxicity secondary to chronic lithium use. We believe that imaging could be extremely helpful for the evaluation of renal toxicity and may even detect preclinical stages of renal parenchymal injury. A combination of different imaging modalities may help clarify findings detected on one modality. C1 [Karaosmanoglu, Ali Devrim; Butros, Selim R.; Arellano, Ronald] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Abdominal Imaging & In, Boston, MA 02115 USA. RP Karaosmanoglu, AD (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Abdominal Imaging & In, Boston, MA 02115 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 12 TC 5 Z9 5 U1 1 U2 11 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD JUL-AUG PY 2013 VL 19 IS 4 BP 299 EP 303 DI 10.5152/dir.2013.097 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173TS UT WOS:000321103300006 PM 23439253 ER PT J AU Keating, NL O'Malley, AJ Freedland, SJ Smith, MR AF Keating, Nancy L. O'Malley, A. James Freedland, Stephen J. Smith, Matthew R. TI Does Comorbidity Influence the Risk of Myocardial Infarction or Diabetes During Androgen-Deprivation Therapy for Prostate Cancer? SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Myocardial infarction; Diabetes ID QUALITY-OF-CARE; CARDIOVASCULAR-DISEASE; RADIATION-THERAPY; SUPPRESSION; MEDICARE; MEN; RADIOTHERAPY; NEOADJUVANT; POPULATION; GOSERELIN AB Background: Androgen-deprivation therapy (ADT) for prostate cancer (PCa) may be associated with cardiovascular disease and diabetes. Some data suggest that men with certain conditions may be more susceptible to developing cardiovascular disease than others. Objective: To assess whether the risk of myocardial infarction (MI) or diabetes during ADT is modified by specific baseline comorbidities. Design, setting, and participants: We conducted a population-based observational study of 185 106 US men >= 66 yr of age diagnosed with local/regional PCa from 1992 to 2007. We assessed comorbidities monthly over the follow-up period. Outcome measurements and statistical analysis: Cox proportional hazards models with time-varying variables assessing incident diabetes or MI. Results and limitations: A total of 49.9% of the men received ADT during follow-up. Among men with no comorbidities, ADT was associated with an increase in the adjusted hazard of MI (adjusted hazard ratio [AHR]: 1.09; 95% confidence interval [CI], 1.02-1.16) and diabetes (AHR: 1.33; 95% CI, 1.27-1.39). Risks of MI and diabetes were similarly increased among men with and without specific comorbid illnesses (p > 0.10 for all interactions, with one exception). Previous MI, congestive heart failure, peripheral arterial disease, stroke, hypertension, chronic obstructive pulmonary disease, and renal disease were associated with new MI and diabetes, and obesity and rheumatologic disease were also associated with diabetes. Limitations include the observational study design, reliance on administrative data to ascertain outcomes, and lack of information on risk factors such as smoking and family history. Conclusions: Traditional risk factors for MI and diabetes were also associated with developing these conditions during ADT but did not significantly modify the risk attributable to ADT. Strategies to screen and prevent diabetes and cardiovascular disease in men with PCa should be similar to the strategies recommended for the general population. (c) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.; O'Malley, A. James] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Freedland, Stephen J.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Dept Surg Urol & Pathol, Duke Prostate Ctr, Durham, NC USA. [Smith, Matthew R.] Massachusetts Gen Hosp MRS, Div Hematol & Oncol, Boston, MA USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Prostate Cancer Foundation FX The study was funded by the Prostate Cancer Foundation, who had no role in the analysis or reporting of the study. NR 29 TC 30 Z9 31 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JUL PY 2013 VL 64 IS 1 BP 159 EP 166 DI 10.1016/j.eururo.2012.04.035 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 166WA UT WOS:000320588800038 PM 22537796 ER PT J AU Gilbert, J Lee, JW Argiris, A Haigentz, M Feldman, LE Jang, M Arun, P Van Waes, C Forastiere, AA AF Gilbert, Jill Lee, Ju Whei Argiris, Athanassios Haigentz, Missak, Jr. Feldman, Lawrence Eric Jang, Minyoung Arun, Pattatheyil Van Waes, Carter Forastiere, Arlene A. TI Phase II 2-arm trial of the proteasome inhibitor, PS-341 (bortezomib) in combination with irinotecan or PS-341 alone followed by the addition of irinotecan at time of progression in patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck (E1304): A trial of the Eastern Cooperative Oncology Group SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE head and neck cancer; chemotherapy; bortezomib; irinotecan; phase II ID FACTOR-KAPPA-B; TUMOR-CELLS; CANCER; THERAPY; DOCETAXEL; CISPLATIN; ACTIVATOR; PATHWAY; EGFR AB Background Constitutive activation of nuclear factor B (NF-B) is associated with poor prognosis. Irinotecan demonstrates single-agent activity in head and neck cancer but activates NF-B, promoting cell survival and resistance. Bortezomib is a proteasome inhibitor that inactivates NF-B. Patients and Methods We performed a randomized phase II trial of bortezomib on days 1, 4, 8, and 11 and irinotecan on days 1 and 8 of each 21-day cycle or single-agent bortezomib on days 1, 4, 8, and 11 on a 21-day cycle. The addition of irinotecan to bortezomib was allowed in patients who progressed on bortezomib alone. Results The response rate of bortezomib and irinotecan was 13%. One patient had a partial response to bortezomib alone (response rate 3%). No responses were seen in patients with addition of irinotecan at time of progression on bortezomib. Conclusions The bortezomib-based regimens evaluated in this study have minimal activity in recurrent or metastatic head and neck cancer. Head Neck, 2013 C1 [Gilbert, Jill] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Lee, Ju Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Argiris, Athanassios] Univ Pittsburgh, Pittsburgh, PA USA. [Haigentz, Missak, Jr.] Montefiore Hosp & Med Ctr, Bronx, NY USA. [Feldman, Lawrence Eric] Univ Illinois Chicago MBCCOP, Chicago, IL USA. [Jang, Minyoung; Arun, Pattatheyil; Van Waes, Carter] NIDCD, Head & Neck Surgey Branch, NIH, Bethesda, MD USA. [Forastiere, Arlene A.] Johns Hopkins Univ, Baltimore, MD USA. RP Gilbert, J (reprint author), Vanderbilt Univ, Med Ctr, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM jill.gilbert@vanderbilt.edu FU Public Health Service from the National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA39229, CA49957, CA14958, CA16116]; Department of Health and Human Services; Milllennium Pharmaceuticals FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA39229, CA49957, CA14958, CA16116 and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.; Milllennium Pharmaceuticals provided bortezomib for prior preclinical studies6 to C. V. W. and bortezomib and funding to NCI for a prior clinical trial and correlative studies.16 NR 18 TC 10 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUL PY 2013 VL 35 IS 7 BP 942 EP 948 DI 10.1002/hed.23046 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 168RI UT WOS:000320723000013 PM 22791234 ER PT J AU Fayaz, HC Haas, N Kellam, J Bavonratanavech, S Parvizi, J Dyer, G Pohlemann, T Jerosch, J Prommersberger, KJ Pape, HC Smith, M Vrahas, M Perka, C Siebenrock, K Elhassan, B Moran, C Jupiter, JB AF Fayaz, Hangama C. Haas, Norbert Kellam, James Bavonratanavech, Suthorn Parvizi, Javad Dyer, George Pohlemann, Tim Jerosch, Joerg Prommersberger, Karl-Josef Pape, Hans Christoph Smith, Malcolm Vrahas, Marc Perka, Carsten Siebenrock, Klaus Elhassan, Bassem Moran, Christopher Jupiter, Jesse B. TI Improvement of research quality in the fields of orthopaedics and trauma-a global perspective SO INTERNATIONAL ORTHOPAEDICS LA English DT Review ID EVIDENCE-BASED MEDICINE; JOINT-SURGERY; IMPACT FACTOR; USERS GUIDES; METAANALYSES; PUBLICATIONS; PRINCIPLES; GUIDELINES; JOURNALS; LEVEL AB The international orthopaedic community aims to achieve the best possible outcome for patient care by constantly modifying surgical techniques and expanding the surgeon's knowledge. These efforts require proper reflection within a setting that necessitates a higher quality standard for global orthopaedic publication. Furthermore, these techniques demand that surgeons acquire information at a rapid rate while enforcing higher standards in research performance. An international consensus exists on how to perform research and what rules should be considered when publishing a scientific paper. Despite this global agreement, in today's "Cross Check Era", too many authors do not give attention to the current standards of systematic research. Thus, the purpose of this paper is to describe these performance standards, the available choices for orthopaedic surgeons and the current learning curve for seasoned teams of researchers and orthopaedic surgeons with more than three decades of experience. These lead to provide an accessible overview of all important aspects of the topics that will significantly influence the research development as we arrive at an important globalisation era in orthopaedics and trauma-related research. C1 [Fayaz, Hangama C.; Smith, Malcolm; Vrahas, Marc; Jupiter, Jesse B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Haas, Norbert; Perka, Carsten] Charite, Dept Orthopaed Surg, D-13353 Berlin, Germany. [Kellam, James] Carolinas Med Ctr, Dept Orthopaed Surg, Charlotte, NC 28204 USA. [Bavonratanavech, Suthorn] Bangkok Hosp, Dept Orthoped Surg, Bangkok 10310, Thailand. [Parvizi, Javad] Rothman Inst Ctr City Philadelphia, Rothman Inst Orthoped, Philadelphia, PA 19107 USA. [Dyer, George] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Pohlemann, Tim] Univ Saarland, Dept Trauma Hand & Reconstruct Surg, Homburg, Germany. [Jerosch, Joerg] Johanna Etienne Hosp, Dept Orthopaed Surg, D-41462 Neuss, Germany. [Prommersberger, Karl-Josef] Rhon Klinikum, Clin Hand Surg, Bad Neustadt an der Saale, Germany. [Pape, Hans Christoph] Univ Aachen, Med Ctr, Dept Orthopaed Trauma, D-52074 Aachen, Germany. [Siebenrock, Klaus] Univ Bern, Inselspital, Dept Orthopaed Surg, CH-3010 Bern, Switzerland. [Elhassan, Bassem] Mayo Clin, Dept Orthoped Surg, Rochester, MN 55905 USA. [Moran, Christopher] Univ Nottingham Hosp, Dept Trauma & Orthopaed, Nottingham NG7 2UH, England. RP Fayaz, HC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM dr.hana.fayaz@hotmail.de NR 39 TC 1 Z9 1 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD JUL PY 2013 VL 37 IS 7 BP 1205 EP 1212 DI 10.1007/s00264-013-1897-2 PG 8 WC Orthopedics SC Orthopedics GA 167UL UT WOS:000320660500001 PM 23689761 ER PT J AU Huijbers, W Schultz, AP Vannini, P McLaren, DG Wigman, SE Ward, AM Hedden, T Sperling, RA AF Huijbers, Willem Schultz, Aaron P. Vannini, Patrizia McLaren, Donald G. Wigman, Sarah E. Ward, Andrew M. Hedden, Trey Sperling, Reisa A. TI The Encoding/Retrieval Flip: Interactions between Memory Performance and Memory Stage and Relationship to Intrinsic Cortical Networks SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSTERIOR CINGULATE CORTEX; RESTING HUMAN BRAIN; EVENT-RELATED FMRI; FUNCTIONAL CONNECTIVITY; PARIETAL CORTEX; ALZHEIMERS-DISEASE; DEFAULT NETWORK; EXECUTIVE FUNCTIONS; SUBSEQUENT MEMORY; COGNITIVE CONTROL AB fMRI studies have linked the posteromedial cortex to episodic learning (encoding) and remembering (retrieval) processes. The posteromedial cortex is considered part of the default network and tends to deactivate during encoding but activate during retrieval, a pattern known as the encoding/retrieval flip. Yet, the exact relationship between the neural correlates of memory performance (hit/miss) and memory stage (encoding/retrieval) and the extent of overlap with intrinsic cortical networks remains to be elucidated. Using task-based fMRI, we isolated the pattern of activity associated with memory performance, memory stage, and the interaction between both. Using resting-state fMRI, we identified which intrinsic large-scale functional networks overlapped with regions showing task-induced effects. Our results demonstrated an effect of successful memory performance in regions associated with the control network and an effect of unsuccessful memory performance in the ventral attention network. We found an effect of memory retrieval in brain regions that span the default and control networks. Finally, we found an interaction between memory performance and memory stage in brain regions associated with the default network, including the posteromedial cortex, posterior parietal cortex, and parahippocampal cortex. We discuss these findings in relation to the encoding/retrieval flip. In general, the findings demonstrate that task-induced effects cut across intrinsic cortical networks. Furthermore, regions within the default network display functional dissociations, and this may have implications for the neural underpinnings of age-related memory disorders. C1 [Huijbers, Willem; Vannini, Patrizia; McLaren, Donald G.; Hedden, Trey; Sperling, Reisa A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Huijbers, Willem; Vannini, Patrizia; Sperling, Reisa A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Huijbers, Willem; Schultz, Aaron P.; Vannini, Patrizia; McLaren, Donald G.; Wigman, Sarah E.; Ward, Andrew M.; Hedden, Trey; Sperling, Reisa A.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Schultz, Aaron P.; McLaren, Donald G.; Wigman, Sarah E.; Ward, Andrew M.; Hedden, Trey; Sperling, Reisa A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Huijbers, W (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM huijbers@nmr.mgh.harvard.edu OI Ward, Andrew/0000-0001-6948-4814; McLaren, Donald/0000-0002-0566-4610 FU European Molecular Biology Organization [ALTF 318-2011]; Marie Curie Fellowship from the European Union [FP7-PEOPLE-2007-4-1-IOF]; Swedish Brain Foundation; Swedish Society for Medicine; National Institutes of Health [K01 AG040197, K24 AG035007, R01 AG027435-S1, P01AG036694, P50AG00513421]; Alzheimer's Association [IIRG-06-27374]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896] FX This work was supported by the European Molecular Biology Organization: ALTF 318-2011 (W. H.), the Marie Curie Fellowship: FP7-PEOPLE-2007-4-1-IOF from the European Union (P. V.), the Swedish Brain Foundation and Swedish Society for Medicine (P. V.), the National Institutes of Health: K01 AG040197 (T. H.), K24 AG035007 (R. S.), R01 AG027435-S1 (R. S.), P01AG036694 (R. S.), P50AG00513421 (R. S.), and the Alzheimer's Association: IIRG-06-27374 (R. S.). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. NR 66 TC 15 Z9 15 U1 0 U2 11 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 2013 VL 25 IS 7 BP 1163 EP 1179 DI 10.1162/jocn_a_00366 PG 17 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 155GM UT WOS:000319735800014 PM 23384193 ER PT J AU Hsieh, YH Lin, HJ Hsieh, JJ Tseng, KC Tseng, CW Hung, TH Leung, FW AF Hsieh, Yu-Hsi Lin, Hwai-Jeng Hsieh, Jin-Jian Tseng, Kuo-Chih Tseng, Chih-Wei Hung, Tsung-Hsing Leung, Felix W. TI Meperidine as the single sedative agent during esophagogastroduodenoscopy, a double-blind, randomized, controlled study SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE esophagogastroduodenoscopy; meperidine; minimal sedation ID UPPER GASTROINTESTINAL ENDOSCOPY; UNSEDATED ESOPHAGOGASTRODUODENOSCOPY; PHARYNGEAL ANESTHESIA; CONSCIOUS SEDATION; CONTROLLED-TRIAL; LIDOCAINE SPRAY; GI ENDOSCOPY; MIDAZOLAM; GASTROSCOPY; COMBINATION AB Background and Aim In Taiwan, unsedated esophagogastroduodenoscopy (EGD) is widely used, but it is uncomfortable for some patients. While meperidine has been adopted in colonoscopy, its use in EGD has not received extensive attention. This was a prospective study to investigate the use of meperidine as a single sedative agent during EGD. Methods One hundred and forty patients were randomized to receive either 25-mg meperidine (n=70) or placebo (n=70) by intramuscular injection before EGD. The primary outcome was patient discomfort scores. The secondary outcomes included patient, endoscopist, and EGD-related variables. Results Patients in the meperidine group reported less discomfort during esophageal intubation (median score of 2.0 and interquartile range [IQR] of 0-4.0 vs median score of 4.8 and IQR of 1.7-7.0, respectively; P<0.001) and during the procedure (median score of 1.0 [IQR 0-3.1] vs 3.5 [IQR 0-5.6], P=0.001) than patients in the placebo group. The endoscopist found patients in the meperidine group had better tolerance during esophageal intubation (median score of 1.0 [IQR 0-2.0] vs 2.0 [IQR 1.0-3.0], P=0.021) and during the procedure (median score of 0 [IQR 0-1.0] vs 1.0 [IQR 0-3.0], P<0.001). After the procedure more patients in the meperidine group (71.4% vs 35.7%, P<0.001) experienced self-limited dizziness that prolonged recovery by approximate to 3.7min. Conclusions After receiving meperidine injection, patients had better tolerance and less discomfort during diagnostic EGD (NCT01547520). C1 [Hsieh, Yu-Hsi; Tseng, Kuo-Chih; Tseng, Chih-Wei; Hung, Tsung-Hsing] Buddhist Dalin Tzu Chi Gen Hosp, Div Gastroenterol, Dept Med, Dalin 622, Chia Yi, Taiwan. [Hsieh, Jin-Jian] Natl Chung Cheng Univ, Dept Math, Chiayi, Taiwan. [Hsieh, Yu-Hsi; Tseng, Kuo-Chih; Tseng, Chih-Wei; Hung, Tsung-Hsing] Buddhist Tzu Chi Univ, Sch Med, Hwalien, Taiwan. [Lin, Hwai-Jeng] Taipei Med Univ Hosp, Div Gastroenterol & Hepatol, Dept Internal Med, Taipei, Taiwan. [Lin, Hwai-Jeng] Taipei Med Univ, Sch Med, Taipei, Taiwan. [Leung, Felix W.] Sepulveda Ambulatory Care Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, North Hill, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hsieh, YH (reprint author), Buddhist Dalin Tzu Chi Gen Hosp, Div Gastroenterol, Dept Med, 2 Min Sheng Rd, Dalin 622, Chia Yi, Taiwan. EM hsieh.yuhsi@msa.hinet.net OI Tseng, Chih-Wei/0000-0002-6951-4646 FU Buddhist Dalin Tzu Chi General Hospital FX This study was supported by research funds from Buddhist Dalin Tzu Chi General Hospital. NR 23 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JUL PY 2013 VL 28 IS 7 BP 1167 EP 1173 DI 10.1111/jgh.12183 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 168RC UT WOS:000320722200017 PM 23431993 ER PT J AU Li, X Kim, J Song, B Finzi, A Pacheco, B Sodroski, J AF Li, Xing Kim, Jonghwa Song, Byeongwoon Finzi, Andres Pacheco, Beatriz Sodroski, Joseph TI Virus-Specific Effects of TRIM5 alpha(rh) RING Domain Functions on Restriction of Retroviruses SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; E3 UBIQUITIN LIGASES; IMMUNODEFICIENCY-VIRUS; PRIMATE TRIM5-ALPHA; OLD-WORLD; REVERSE TRANSCRIPTION; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; SEQUENCE VARIATION; HIV-1 RESTRICTION AB The tripartite motif protein TRIM5 alpha restricts particular retrovirus infections by binding to the incoming capsid and inhibiting the early stage of virus infection. The TRIM5 alpha RING domain exhibits E3 ubiquitin ligase activity and assists the higher-order association of TRIM5 alpha dimers, which promotes capsid binding. We characterized a panel of RING domain mutants of the rhesus monkey TRIM5 alpha (TRIM5 alpha(rh)) protein. The RING domain function that significantly contributed to retroviral restriction depended upon the restricted virus. The E3 ubiquitin ligase activity of the RING domain contributes to the potency of HIV-1 restriction. Nonetheless, TRIM5 alpha(rh) mutants without detectable E3 ubiquitin ligase activity still blocked reverse transcription and inhibited HIV-1 infection at a moderate level. When TRIM5 alpha(rh) capsid binding was weakened by substitution with a less efficient B30.2/SPRY domain, the promotion of higher-order association by the RING domain was more important to HIV-1 restriction than its E3 ubiquitin ligase activity. For the restriction of N-tropic murine leukemia virus (N-MLV) and equine infectious anemia virus (EIAV) infection, promotion of higher-order association represented the major contribution of the RING domain. Thus, both identity of the target virus and the B30.2/SPRY domain-mediated affinity for the viral capsid determine the relative contribution of the two known RING domain functions to TRIM5 alpha restriction of retrovirus infection. C1 [Li, Xing; Kim, Jonghwa; Finzi, Andres; Pacheco, Beatriz; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Sodroski, Joseph] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Finzi, Andres] Univ Montreal, Ctr Hosp, St Luc Hosp, Montreal, PQ, Canada. [Pacheco, Beatriz] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. [Song, Byeongwoon] Ctr Biol Mol Severo Ochoa, Madrid, Spain. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [AI063987]; Center for AIDS Research Award [AI06354]; International AIDS Vaccine Initiative FX We acknowledge the support of the National Institutes of Health (AI063987 and a Center for AIDS Research Award, AI06354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. NR 61 TC 12 Z9 16 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2013 VL 87 IS 13 BP 7234 EP 7245 DI 10.1128/JVI.00620-13 PG 12 WC Virology SC Virology GA 160JT UT WOS:000320116500004 PM 23637418 ER PT J AU Leblebjian, H DeAngelo, DJ Skirvin, JA Stone, RM Wadleigh, M Werner, L Neuberg, DS Bartel, S McDonnell, AM AF Leblebjian, Houry DeAngelo, Daniel J. Skirvin, J. Andrew Stone, Richard M. Wadleigh, Martha Werner, Lillian Neuberg, Donna S. Bartel, Sylvia McDonnell, Anne M. TI Predictive factors for all-trans retinoic acid-related differentiation syndrome in patients with acute promyelocytic leukemia SO LEUKEMIA RESEARCH LA English DT Article DE Acute promyelocytic leukemia; Differentiation syndrome; All-trans retinoic acid; Retinoic acid syndrome; ATRA ID PROGNOSTIC-FACTORS; MYELOID-LEUKEMIA; ARSENIC TRIOXIDE; PHASE-I; CHEMOTHERAPY; KETOCONAZOLE; INDUCTION; THERAPY; ADULTS; RISK AB All-trans retinoic acid (ATRA) used for the treatment of APL can lead to the development of differentiation syndrome (DS), a potentially life threatening complication. Since ATRA is metabolized by cytochrome P450 (CYP) enzymes, we sought to identify drug interactions that might be associated with a higher risk for the development of DS in addition to other predictive factors related to the incidence of DS. We identified 60 consecutive patients with APL treated at our institution with ATRA from May 2004 until January 2010. Of the 60 patients identified, 29 (48%) developed DS within a median of 5 days (range 1-31) of ATRA initiation. We did not find any difference in overall incidence of DS whether patients were on concurrent CYP 2C8, 2C9 or 3A4 inhibitors, inducers or substrates. In multivariable analysis, higher peripheral blood blast counts on admission (p = 0.04) as well as higher body mass index (p = 0.003) were associated with developing DS. Out of the 29 patients with DS, there were 4 early deaths of which 2 were attributed to DS compared to no early deaths in the patients who did not develop DS (p = 0.05). Regarding disease-related outcomes, only CR rate was different between patients developing DS versus those who did not develop DS. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Leblebjian, Houry; Skirvin, J. Andrew; Werner, Lillian; Neuberg, Donna S.; Bartel, Sylvia] Dana Farber Canc Inst, Dept Pharm Serv, Boston, MA 02115 USA. [DeAngelo, Daniel J.; Stone, Richard M.; Wadleigh, Martha] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Skirvin, J. Andrew; Bartel, Sylvia; McDonnell, Anne M.] Brigham & Womens Hosp, Dept Pharm Serv, Boston, MA 02115 USA. [Skirvin, J. Andrew] Northeastern Univ, Dept Pharm, Boston, MA 02115 USA. [Neuberg, Donna S.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Leblebjian, H (reprint author), Dana Farber Canc Inst, Dept Pharm, 450 Brookline Ave, Boston, MA 02115 USA. EM Houry_Leblebjian@dfci.harvard.edu NR 33 TC 4 Z9 4 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUL PY 2013 VL 37 IS 7 BP 747 EP 751 DI 10.1016/j.leukres.2013.04.011 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 166UF UT WOS:000320583100007 PM 23643326 ER PT J AU Douer, D Zickl, LN Schiffer, CA Appelbaum, FR Feusner, JH Shepherd, L Willman, CL Bloomfield, CD Paietta, E Gallagher, RE Park, JH Rowe, JM Wiernik, PH Tallman, MS AF Douer, Dan Zickl, Lynette N. Schiffer, Charles A. Appelbaum, Fredrick R. Feusner, James H. Shepherd, Lois Willman, Cheryl L. Bloomfield, Clara D. Paietta, Elisabeth Gallagher, Robert E. Park, Jae H. Rowe, Jacob M. Wiernik, Peter H. Tallman, Martin S. TI All-trans retinoic acid and late relapses in acute promyelocytic leukemia: Very long-term follow-up of the North American Intergroup Study I0129 SO LEUKEMIA RESEARCH LA English DT Article DE Acute promyelocytic leukemia; All-trans retinoic acid; Late relapse ID EARLY DEATH RATE; MAINTENANCE THERAPY; TRANSRETINOIC ACID; GROUP EXPERIENCE; EVENT-FREE; RAR-ALPHA; TRIAL; CHEMOTHERAPY; SURVIVAL; ADULTS AB We report a long-term follow-up (median 11.8 years) of the First North American Intergroup Study. 379 patients were randomized to induction with ATRA or to chemotherapy. All complete responders (CR) received consolidation chemotherapy, then randomized to 1 year ATRA or observation. 245 patients received ATRA sometime during the study: 195 (80%) achieved a CR. Nine (4.6%) relapsed late (>3 years from CR), the last occurred after 4.6 years; 7 of them were still alive after 5.5-15 years. In APL patients, late relapses are uncommon, and those who sustain CR >5 years can be considered cured. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Douer, Dan; Park, Jae H.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Weill Cornell Med Coll, New York, NY 10065 USA. [Zickl, Lynette N.] Dana Farber Canc Inst, Ctr Stat, Boston, MA 02115 USA. [Schiffer, Charles A.] Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. [Appelbaum, Fredrick R.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Feusner, James H.] Childrens Hosp & Res Ctr, Oakland, CA USA. [Shepherd, Lois] Queens Univ, Natl Canc Inst, Kingston, ON, Canada. [Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Gallagher, Robert E.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr Jerusalem, Dept Hematol, Jerusalem, Israel. [Wiernik, Peter H.] St Lukes Roosevelt Hosp, New York, NY USA. [Wiernik, Peter H.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. RP Douer, D (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10065 USA. EM douer@mskcc.org FU Public Health Service Grant [CA21115, CA23318, CA66636, CA17145, CA14958, CA77658, CA32102, CA 37027, CA12213]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services; [CA021115]; [CA114737]; [CA56771] FX This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA21115, CA23318, CA66636, CA17145, CA14958, CA77658, CA32102, CA 37027, CA12213 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Research support for the study: CA021115 and CA114737 were awarded to EP and CA56771 to REG. NR 33 TC 15 Z9 15 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUL PY 2013 VL 37 IS 7 BP 795 EP 801 DI 10.1016/j.leukres.2013.03.001 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 166UF UT WOS:000320583100015 PM 23528262 ER PT J AU Richardson, PG Mitsiades, CS Laubach, JP Hajek, R Spicka, I Dimopoulos, MA Moreau, P Siegel, DS Jagannath, S Anderson, KC AF Richardson, Paul G. Mitsiades, Constantine S. Laubach, Jacob P. Hajek, Roman Spicka, Ivan Dimopoulos, Meletios A. Moreau, Philippe Siegel, David S. Jagannath, Sundar Anderson, Kenneth C. TI Preclinical data and early clinical experience supporting the use of histone deacetylase inhibitors in multiple myeloma SO LEUKEMIA RESEARCH LA English DT Review DE Multiple myeloma; Histone deacetylase; Histone deacetylase inhibitor; Proteasome inhibitor; Immunomodulatory drug; Bortezomib ID ENDOTHELIAL-GROWTH-FACTOR; SUBEROYLANILIDE HYDROXAMIC ACID; REFRACTORY SOLID TUMORS; T-CELL LYMPHOMAS; PHASE-I; HDAC INHIBITORS; PANOBINOSTAT LBH589; CANCER-THERAPY; ANTITUMOR-ACTIVITY; ORAL PANOBINOSTAT AB Histone deacetylases (HDACs) mediate protein acetylation states, which in turn regulate normal cellular processes often dysregulated in cancer. These observations led to the development of HDAC inhibitors that target tumors through multiple effects on protein acetylation. Clinical evidence demonstrates that treatment with HDAC inhibitors (such as vorinostat, panobinostat, and romidepsin) in combination with other antimyeloma agents (such as proteasome inhibitors and immunomodulatory drugs) has promising antitumor activity in relapsed/refractory multiple myeloma patients. This mini-review highlights the role of protein acetylation in the development of cancers and the rationale for the use of HDAC inhibitors in this patient population. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Richardson, Paul G.; Mitsiades, Constantine S.; Laubach, Jacob P.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Hajek, Roman] Univ Ostrava, Fac Med, CZ-70103 Ostrava, Czech Republic. [Hajek, Roman] Fac Hosp Ostrava, Ostrava, Czech Republic. [Spicka, Ivan] Charles Univ Prague, Prague, Czech Republic. [Dimopoulos, Meletios A.] Univ Athens, Dept Therapeut, Athens, Greece. [Moreau, Philippe] Ctr Hosp Univ Hotel Dieu, Nantes, France. [Siegel, David S.] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Jagannath, Sundar] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mailstop Dana 1B02, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu RI richard, chrystelle/K-8595-2015 FU Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Whitehouse Station, NJ); Amgen; AVEO Pharmaceuticals, Inc.; EMD Serono; Sunesis Pharmaceuticals; Gloucester Pharmaceuticals; Genzyme; Johnson Johnson; Celgene Corporation and Millennium: The Takeda Oncology Company FX Medical writing and editorial assistance was provided by Joseph J. Abrajano, PhD, and Kakuri M. Omari, PhD, of Integrus Scientific, a division of Medicus International New York (New York, NY). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Whitehouse Station, NJ). The authors were fully responsible for all content and editorial decisions and received no financial support or other compensation related to the development of the manuscript.; P.R. has served as an advisor for Celgene Corporation, Millennium: The Takeda Oncology Company, Johnson & Johnson, Bristol-Myers Squibb, Novartis, Keryx Biopharmaceuticals, Inc., and Nereus Pharmaceuticals. CSM has served as a consultant for Millennium: The Takeda Oncology Company, Novartis, Bristol-Myers Squibb, Merck & Co., Inc., Kosan Biosciences, Inc., and Pharmion Corporation, and has received grants from Amgen, AVEO Pharmaceuticals, Inc., EMD Serono, Sunesis Pharmaceuticals, Gloucester Pharmaceuticals, Genzyme, and Johnson & Johnson. He also has patents with and has received royalties from Pharma-Mar. R. H. has developed educational presentations for Merck & Co., Inc., Celgene Corporation, and Janssen-Cilag. I. S. is a member of the advisory board for Celgene Corporation (Czech Republic) and has served as a consultant and received honoraria for lectures from Janssen-Cilag (Czech Republic), Celgene Corporation (Czech Republic), and Novartis (Czech Republic). M. D. has served as a consultant for Celgene Corporation, Merck & Co., Inc., and Ortho Biotech, and has received honoraria for lectures from Celgene Corporation. P. M. has served as an advisor for Celgene Corporation, Millennium: The Takeda Oncology Company, Janssen, and Bristol-Myers Squibb. D. S. has served as a consultant for Celgene Corporation, Millennium: The Takeda Oncology Company, Merck & Co., Inc., and Novartis, and has received grants and honoraria for lectures from Celgene Corporation and Millennium: The Takeda Oncology Company. S.J. has served as a consultant for Celgene Corporation, Johnson & Johnson, Janssen Pharmaceuticals, Inc., and Merck & Co., Inc., and has received honoraria for lectures from Clinical Care Options, LLC, Educational Concepts Group, Envision Communications, Imedex, LLC, and Medical Learning Institute. K. A. has served as a consultant for Celgene Corporation, Novartis, Millennium: The Takeda Oncology Company, Bristol-Myers Squibb, Merck & Co., Inc., and Onyx Pharmaceuticals, and is the founder of Acetylon Pharmaceuticals, Inc. J.L. has no conflicts of interest to disclose. NR 102 TC 27 Z9 29 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUL PY 2013 VL 37 IS 7 BP 829 EP 837 DI 10.1016/j.leukres.2013.03.006 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 166UF UT WOS:000320583100020 PM 23582718 ER PT J AU Keil, B Blau, JN Biber, S Hoecht, P Tountcheva, V Setsompop, K Triantafyllou, C Wald, LL AF Keil, Boris Blau, James N. Biber, Stephan Hoecht, Philipp Tountcheva, Veneta Setsompop, Kawin Triantafyllou, Christina Wald, Lawrence L. TI A 64-channel 3T array coil for accelerated brain MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; phased-array coil; brain imaging; parallel imaging ID PHASED-ARRAY; HEAD COIL; SENSITIVITY; SIGNAL; TESLA; DESIGN AB A 64-channel brain array coil was developed and compared to a 32-channel array constructed with the same coil former geometry to precisely isolate the benefit of the 2-fold increase in array coil elements. The constructed coils were developed for a standard clinical 3T MRI scanner and used a contoured head-shaped curved former around the occipital pole and tapered in at the neck to both improve sensitivity and patient comfort. Additionally, the design is a compact, split-former design intended for robust daily use. Signal-to-noise ratio and noise amplification (G-factor) for parallel imaging were quantitatively evaluated in human imaging and compared to a size and shape-matched 32-channel array coil. For unaccelerated imaging, the 64-channel array provided similar signal-to-noise ratio in the brain center to the 32-channel array and 1.3-fold more signal-to-noise ratio in the brain cortex. Reduced noise amplification during highly parallel imaging of the 64-channel array provided the ability to accelerate at approximately one unit higher at a given noise amplification compared to the sized-matched 32-channel array. For example, with a 4-fold acceleration rate, the central brain and cortical signal-to-noise ratio of the 64-channel array was 1.2- and 1.4-fold higher, respectively, compared to the 32-channel array. The characteristics of the coil are demonstrated in accelerated brain imaging. Magn Reson Med, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Keil, Boris; Blau, James N.; Tountcheva, Veneta; Setsompop, Kawin; Triantafyllou, Christina; Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Keil, Boris; Setsompop, Kawin; Triantafyllou, Christina; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Biber, Stephan] Siemens Healthcare, Erlangen, Germany. [Hoecht, Philipp] Siemens Med Solut, Charlestown, MA USA. [Triantafyllou, Christina] MIT, McGovern Inst Brain Res, Cambridge, MA USA. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Keil, B (reprint author), Harvard Univ, AA Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, 149 13th St, Charlestown, MA 02129 USA. EM keil@nmr.mgh.harvard.edu RI Keil, Boris/P-1411-2014; Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; FU National Institutes of Health [U01MH093765, K99EB012107, P41RR14075] FX Grant sponsor: National Institutes of Health; Grant numbers: U01MH093765, K99EB012107 and P41RR14075. NR 30 TC 31 Z9 32 U1 1 U2 7 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 JUL PY 2013 VL 70 IS 1 BP 248 EP 258 DI 10.1002/mrm.24427 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169NB UT WOS:000320785900029 PM 22851312 ER PT J AU Darr, EA Randolph, GW AF Darr, E. Ashlie Randolph, Gregory W. TI Management of laryngeal nerves and parathyroid glands at thyroidectomy SO ORAL ONCOLOGY LA English DT Article ID SURGICAL ANATOMY; EXTERNAL BRANCH; SURGERY; PARALYSIS C1 [Darr, E. Ashlie; Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Otolaryngology Head & Neck Surg, Massachusetts Eye & Ear Infirm,Div Thyroid & Para, Cambridge, MA 02138 USA. RP Darr, EA (reprint author), Harvard Univ, Sch Med, Dept Otolaryngology Head & Neck Surg, Massachusetts Eye & Ear Infirm,Div Thyroid & Para, Cambridge, MA 02138 USA. EM ashlie.darr@gmail.com NR 30 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD JUL PY 2013 VL 49 IS 7 BP 665 EP 670 DI 10.1016/j.oraloncology.2013.03.438 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 166UX UT WOS:000320585100006 PM 23597767 ER PT J AU Jarcho, JM Feier, NA Bert, A Labus, JA Lee, M Stains, J Ebrat, B Groman, SM Tillisch, K Brody, AL London, ED Mandelkern, MA Mayer, EA AF Jarcho, Johanna M. Feier, Natasha A. Bert, Alberto Labus, Jennifer A. Lee, Maunoo Stains, Jean Ebrat, Bahar Groman, Stephanie M. Tillisch, Kirsten Brody, Arthur L. London, Edythe D. Mandelkern, Mark A. Mayer, Emeran A. TI Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain SO PAIN LA English DT Article DE PET; NK-1 receptor; Irritable bowel syndrome; Inflammatory bowel disease; Somatic pain; Quality of life ID IRRITABLE-BOWEL-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; QUALITY-OF-LIFE; SUBSTANCE-P; NK1 RECEPTOR; SPINAL-CORD; HUMAN BRAIN; INFLAMMATORY PAIN; PLACEBO ANALGESIA; PERSISTENT PAIN AB Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters. PET with [F-18] SPA-RQ was used to measure NK-1R availability by quantifying binding potential (BP) in the 3 groups. Exploratory correlation analyses were performed to detect associations between NK-1R BP and physical symptoms. Compared to HCs, IBD patients had NK-1R BP deficits across a widespread network of cortical and subcortical regions. IBS patients had similar, but less pronounced deficits. BP in a subset of these regions was robustly related to discrete clinical parameters in each patient population. Widespread deficits in NK-1R BP occur in IBD and, to a lesser extent, IBS; however, discrete clinical parameters relate to NK-1R BP in each patient population. This suggests that potential pharmacological interventions that target NK-1R signaling may be most effective for treating distinct symptoms in IBD and IBS. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Jarcho, Johanna M.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Jarcho, Johanna M.; Feier, Natasha A.; Labus, Jennifer A.; Lee, Maunoo; Stains, Jean; Ebrat, Bahar; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA 90095 USA. [Feier, Natasha A.] McGill Univ, Fac Dent, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada. [Bert, Alberto] SpA, Med Imaging Lab Im3D, Turin, Italy. [Groman, Stephanie M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Brody, Arthur L.; London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Brody, Arthur L.; London, Edythe D.; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [London, Edythe D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, CHS 42-210 MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu OI Bert, Alberto/0000-0001-8391-7508; Jarcho, Johanna/0000-0001-9075-6968 FU National Institutes of Health [F31-DA021951, T32-MH017140, F31-DA028812, NIH AT00268]; Tobacco-Related Disease Research Program [19XT-0135]; Department of Veterans Affairs, Office of Research and Development (Merit Review Award) FX This work was supported in part by National Institutes of Health Grants F31-DA021951, T32-MH017140 (J.M.J.), F31-DA028812 (S.M.G.), NIH AT00268 (E.A.M.), and endowments from the Marjorie Greene Family Trust and National Institute on Drug Abuse (A.L.B. [R01 DA20872]), the Tobacco-Related Disease Research Program (A.L.B. [19XT-0135]), the Department of Veterans Affairs, Office of Research and Development (Merit Review Award [A.L.B.]), and the Thomas P. and Katherine K. Pike Chair in Addiction Studies (E.D.L.). NR 85 TC 12 Z9 12 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2013 VL 154 IS 7 BP 987 EP 996 DI 10.1016/j.pain.2013.02.026 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 166XD UT WOS:000320592200007 PM 23582152 ER PT J AU Haq, R Fisher, DE AF Haq, Rizwan Fisher, David E. TI Targeting melanoma by small molecules: challenges ahead SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Review DE melanoma; therapeutics; targeted drug delivery ID RESEARCH-AND-DEVELOPMENT; MALIGNANT-MELANOMA; BETA-CATENIN; CANCER-CELLS; SYSTEMATIC IDENTIFICATION; DRUG-SENSITIVITY; GENE-EXPRESSION; RAF INHIBITORS; NEURAL CREST; BRAF AB Significant progress has been made in targeting melanoma using small molecule inhibitors, but challenges remain. Here we describe the history of screening approaches in melanoma and their limitations. We propose several approaches to refine our screening models to enhance the discovery process. It is hoped that this discussion will stimulate further improvements in our development of small molecules inhibitors for treatment of melanoma patients. C1 [Fisher, David E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dfisher3@partners.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 65 TC 3 Z9 3 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD JUL PY 2013 VL 26 IS 4 DI 10.1111/pcmr.12109 PG 7 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 171UP UT WOS:000320955300010 PM 23611259 ER PT J AU Ramon, M Ruelens, P Li, Y Sheen, J Geuten, K Rolland, F AF Ramon, Matthew Ruelens, Philip Li, Yi Sheen, Jen Geuten, Koen Rolland, Filip TI The hybrid Four-CBS-Domain KIN subunit functions as the canonical subunit of the plant energy sensor SnRK1 SO PLANT JOURNAL LA English DT Article DE energy signaling; SnRK1; SNF1; AMPK; subunit; Arabidopsis thaliana; Saccharomyces cerevisiae ID ACTIVATED-PROTEIN-KINASE; GLYCOGEN-BINDING DOMAIN; BETA-SUBUNITS; SACCHAROMYCES-CEREVISIAE; ARABIDOPSIS-THALIANA; MEDICAGO-TRUNCATULA; GLUCOSE REPRESSION; STARCH METABOLISM; GENE-EXPRESSION; BATEMAN DOMAINS AB The AMPK/SNF1/SnRK1 protein kinases are a family of ancient and highly conserved eukaryotic energy sensors that function as heterotrimeric complexes. These typically comprise catalytic subunits and regulatory and subunits, the latter function as the energy-sensing modules of animal AMPK through adenosine nucleotide binding. The ability to monitor accurately and adapt to changing environmental conditions and energy supply is essential for optimal plant growth and survival, but mechanistic insight in the plant SnRK1 function is still limited. In addition to a family of -like proteins, plants also encode a hybrid protein that combines the Four-Cystathionine -synthase (CBS)-domain (FCD) structure in subunits with a glycogen-binding domain (GBD), typically found in subunits. We used integrated functional analyses by ectopic SnRK1 complex reconstitution, yeast mutant complementation, in-depth phylogenetic reconstruction, and a seedling starvation assay to show that only the hybrid KIN protein that recruited the GBD around the emergence of the green chloroplast-containing plants, acts as the canonical subunit required for heterotrimeric complex formation. Mutagenesis and truncation analysis further show that complex interaction in plant cells and subunit function in yeast depend on both a highly conserved FCD and a pre-CBS domain, but not the GBD. In addition to novel insight into canonical AMPK/SNF/SnRK1 subunit function, regulation and evolution, we provide a new classification of plant FCD genes as a convenient and reliable tool to predict regulatory partners for the SnRK1 energy sensor and novel FCD gene functions. C1 [Ramon, Matthew; Ruelens, Philip; Li, Yi; Geuten, Koen; Rolland, Filip] Katholieke Univ Leuven, Dept Biol, Plant Mol Biol Lab, B-3001 Louvain, Belgium. [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Rolland, F (reprint author), Katholieke Univ Leuven, Dept Biol, Plant Mol Biol Lab, B-3001 Louvain, Belgium. EM filip.rolland@bio.kuleuven.be FU Fund for Scientific Research - Flanders (FWO); National Science Foundation (NSF) [IOS-0843244]; United States National Institutes of Health (NIH) [R01 GM60493] FX The authors would like to thank Marian Carlson for yeast strains. Research in the Rolland and Geuten labs is supported by the Fund for Scientific Research - Flanders (FWO). Research in the Sheen laboratory is supported by National Science Foundation (NSF) grant IOS-0843244 and United States National Institutes of Health (NIH) grant R01 GM60493. The authors declare to have no conflict of interest. NR 72 TC 24 Z9 24 U1 4 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7412 EI 1365-313X J9 PLANT J JI Plant J. PD JUL PY 2013 VL 75 IS 1 BP 11 EP 25 DI 10.1111/tpj.12192 PG 15 WC Plant Sciences SC Plant Sciences GA 168LV UT WOS:000320708300002 PM 23551663 ER PT J AU Erickson, CA Wink, LK Ray, B Early, MC Stiegelmeyer, E Mathieu-Frasier, L Patrick, V Lahiri, DK McDougle, CJ AF Erickson, Craig A. Wink, Logan K. Ray, Balmiki Early, Maureen C. Stiegelmeyer, Elizabeth Mathieu-Frasier, Lauren Patrick, Vanessa Lahiri, Debomoy K. McDougle, Christopher J. TI Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome SO PSYCHOPHARMACOLOGY LA English DT Article DE Fragile X syndrome; Social withdrawal; Inattention; Hyperactivity; Acamprosate; Brain-derived neurotrophic factor; Brain-derived neurotrophic factor (BDNF); Glutamate; Metabotropic type 5 glutamate receptor (mGluR5); Neurodevelopment; Gamma-aminobutyric acid (GABA); N-methyl-D-aspartic acid (NMDA) ID MOUSE MODEL; GABA(A) RECEPTOR; BDNF LEVELS; GLUTAMATE RECEPTORS; MENTAL-RETARDATION; MESSENGER-RNA; RATING-SCALE; PROTEIN; EXPRESSION; MICE AB Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism. As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts. Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission. We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11.9 years) with FXS. Acamprosate use (mean dose: 1,054 +/- 422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of "very much improved" or "much improved") in nine of 12 (75 %) subjects. Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures. No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate. Additionally, pre- and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment. In our pilot sample, treatment response did not correlate with change in BDNF with treatment. Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity. The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies. Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted. C1 [Erickson, Craig A.; Wink, Logan K.; Ray, Balmiki; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; Lahiri, Debomoy K.; McDougle, Christopher J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Erickson, Craig A.; Wink, Logan K.; Ray, Balmiki; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; Lahiri, Debomoy K.; McDougle, Christopher J.] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [McDougle, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lurie Ctr Autism, Boston, MA USA. [Erickson, Craig A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. RP Erickson, CA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Child & Adolescent Psychiat, Cincinnati, OH 45229 USA. EM craig.erickson@cchmc.org FU Indiana Clinical and Translational Sciences Institute (CTSI); Division of Disability & Rehabilitative Services, Indiana Family and Social Services Administration; National Institute of Health, Indiana University Clinical [KL2 UL1 RR025761]; Translational Sciences Institute Career Development Award; NIH [5R01 AG 018884-10]; NIMH [R01 MH072964, R01 MH077600, R01 MH083739] FX This work is supported by a grant from the Indiana Clinical and Translational Sciences Institute (CTSI; Dr. Erickson). The work is also supported, in part, by the Division of Disability & Rehabilitative Services, Indiana Family and Social Services Administration (Drs. Erickson, Wink); National Institute of Health grant KL2 UL1 RR025761 Indiana University Clinical, and Translational Sciences Institute Career Development Award (Dr. Erickson); NIH grant 5R01 AG 018884-10 (Dr. Lahiri); and NIMH grants R01 MH072964, R01 MH077600, and R01 MH083739 (Dr. McDougle). We would like to thank J.T. Diener, Jennifer Mullett, and Arlene Kohn for their assistance with this project. NR 64 TC 31 Z9 31 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2013 VL 228 IS 1 BP 75 EP 84 DI 10.1007/s00213-013-3022-z PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 163VM UT WOS:000320365100007 PM 23436129 ER PT J AU Gottlieb, DJ Craig, SE Lorenzi, G Heeley, E Redline, S McEvoy, RD Duran-Cantolla, J AF Gottlieb, Daniel J. Craig, Sonya E. Lorenzi-Filho, Geraldo Heeley, Emma Redline, Susan McEvoy, R. Doug Duran-Cantolla, Joaquin TI Sleep Apnea Cardiovascular Clinical Trials-Current Status and Steps Forward: The International Collaboration of Sleep Apnea Cardiovascular Trialists SO SLEEP LA English DT Article DE Cardiovascular disease; clinical trials; sleep apnea ID POSITIVE AIRWAY PRESSURE; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; RISK-FACTOR; FOLLOW-UP; CHOLESTEROL LEVELS; FAILURE; STROKE; MEN; HYPOPNEA AB Sleep apnea is a common chronic disease that is associated with coronary heart disease, stroke, heart failure and mortality, although the ability of sleep apnea treatment to reduce cardiovascular morbidity and mortality has not been demonstrated. In contrast to patients seeking treatment in sleep disorders centers, as many as half of individuals with moderate to severe sleep apnea in the general population do not report excessive sleepiness; however, if treatment of sleep apnea were shown to reduce cardiovascular disease risk, this would provide a strong rationale for treatment of sleep apnea even in the absence of daytime sleepiness. This article summarizes the status of clinical trials evaluating the potential cardiovascular benefits of sleep apnea treatment and discusses the challenges of conducting such trials, and introduces the International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT), a clinical research collaboration formed to foster cardiovascular sleep research. C1 [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Gottlieb, Daniel J.; Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Gottlieb, Daniel J.; Redline, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Craig, Sonya E.] Churchill Hosp, Ctr Resp Med, Sleep Unit, Oxford OX3 7LJ, England. [Lorenzi-Filho, Geraldo] Univ Sao Paulo, Sleep Lab, Div Pulm, Heart Inst InCor, BR-05508 Sao Paulo, Brazil. [Craig, Sonya E.] Univ Sydney, Sydney, NSW 2006, Australia. [McEvoy, R. Doug] Repatriat Gen Hosp, Adelaide Inst Sleep Hlth, Daw Pk, SA, Australia. [McEvoy, R. Doug] Flinders Univ S Australia, Dept Med, Bedford Pk, SA 5042, Australia. [Duran-Cantolla, Joaquin] Univ Basque Country, Bioaraba Res Inst, Vitoria, Spain. [Duran-Cantolla, Joaquin] Univ Basque Country, Sleep Unit, Alava Univ Hosp, Dept Med, Vitoria, Spain. RP Gottlieb, DJ (reprint author), Brigham & Womens Hosp, Div Sleep Med, Program Sleep & Cardiovasc Med, 221 Longwood Ave,BLI 225E, Boston, MA 02115 USA. EM djgottlieb@partners.org RI Duran Cantolla, Joaquin/B-6996-2015 FU Philips Respironics; ResMed Inc.; Fisher and Paykel Healthcare; ResMed Foundation FX This was not an industry supported study. Dr. Gottlieb has served as a consultant to ResMed Corporation. Dr. Heeley and Dr. McEvoy have received research support for the SAVE Trial from Philips Respironics, ResMed Inc., and Fisher and Paykel Healthcare. Dr. Redline has received research support from Philips Respironics, ResMed Foundation, and ResMed Inc. NR 32 TC 17 Z9 17 U1 0 U2 7 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUL 1 PY 2013 VL 36 IS 7 BP 975 EP 980 DI 10.5665/sleep.2790 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 172XG UT WOS:000321039500006 PM 23814333 ER PT J AU Gehrman, P Seelig, AD Jacobson, IG Boyko, EJ Hooper, TI Gackstetter, GD Ulmer, CS Smith, TC AF Gehrman, Philip Seelig, Amber D. Jacobson, Isabel G. Boyko, Edward J. Hooper, Tomoko I. Gackstetter, Gary D. Ulmer, Christi S. Smith, Tyler C. CA Millennium Cohort Study Team TI Predeployment Sleep Duration and Insomnia Symptoms as Risk Factors for New-Onset Mental Health Disorders Following Military Deployment SO SLEEP LA English DT Article DE Stress disorders; post-traumatic; anxiety; depression; sleep ID POSTTRAUMATIC-STRESS-DISORDER; PENN STATE COHORT; MILLENNIUM COHORT; PSYCHIATRIC-DISORDERS; LONGITUDINAL ASSESSMENT; VIETNAM VETERANS; YOUNG-ADULTS; PRIMARY-CARE; PRIME-MD; DEPRESSION AB Study Objectives: To evaluate predeployment sleep duration and insomnia symptoms in relation to the development of mental health symptoms. Design: Longitudinal cohort study. Setting: The Millennium Cohort Study survey is administered via a secure website or US mail. Participants: Data were from 15,204 participants who completed their first deployment between the submissions of 2 consecutive Millennium Cohort questionnaires (2001-2008). Interventions: N/A. Measurements and Results: Using self-reported data from the Millennium Cohort Study we evaluated the association of predeployment sleep duration and insomnia symptoms on the development of new-onset mental disorders among deployers. Multivariable logistic regression was used to estimate the odds of developing posttraumatic stress disorder (PTSD), depression, and anxiety, while adjusting for relevant covariates including combat-related trauma. The study outcomes were assessed using validated instruments, including the PTSD checklist-civilian version, and the PRIME-MD Patient Health Questionnaire. We identified 522 people with new-onset PTSD, 151 with anxiety, and 303 with depression following deployment. In adjusted models, combat-related trauma and predeployment insomnia symptoms were significantly associated with higher odds of developing posttraumatic stress disorder, depression, and anxiety postdeployment. Conclusions: Sleep characteristics, especially insomnia symptoms, are related to the development of mental disorders following military deployments. Assessment of insomnia symptoms predeployment may help to better identify those at highest risk for subsequent adverse mental health outcomes. C1 [Gehrman, Philip] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Seelig, Amber D.; Jacobson, Isabel G.; Smith, Tyler C.] Naval Hlth Res Ctr, Dept Deployment Hlth Res, San Diego, CA 92106 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Hooper, Tomoko I.] Univ Hlth Sci, Uniformed Serv, Dept Prevent Med & Biometr, Bethesda, MD USA. [Ulmer, Christi S.] Durham VA, Durham, NC USA. [Ulmer, Christi S.] Duke Univ, Med Ctr, Durham, NC USA. [Smith, Tyler C.] Natl Univ Technol, Sch Hlth & Human Serv, Dept Community Hlth, San Diego, CA USA. [Smith, Tyler C.] Hlth Sci Ctr, San Diego, CA USA. RP Seelig, AD (reprint author), Naval Hlth Res Ctr, Dept Deployment Hlth Res, 140 Sylvester Rd, San Diego, CA 92106 USA. EM amber.seelig@med.navy.mil FU Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland; Military Operational Medicine Research Program of the US Army Medical Research and Materiel Command, Fort Detrick, Maryland; VA Puget Sound Health Care System; VA Career Development Award [CDA 09-218]; Department of Defense [60002] FX The authors thank the Millennium Cohort Study participants, without whom these analyses would not be possible. We thank Scott Seggerman from the Management Information Division, US Defense Manpower Data Center, Seaside, California; Michelle LeWark from the Naval Health Research Center; and all the professionals from the US Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, Maryland. We appreciate the support of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland.; The Millennium Cohort Study is funded through the Military Operational Medicine Research Program of the US Army Medical Research and Materiel Command, Fort Detrick, Maryland. VA Puget Sound Health Care System provided support for Dr. Boyko's involvement in this research. Dr. Ulmer was supported by a VA Career Development Award (CDA 09-218). The funding organization had no role in the design and conduct of the study; collection, analysis, or preparation of data; or preparation, review, or approval of the manuscript.; This article represents report 12-03, supported by the Department of Defense, under work unit number 60002. The views expressed in this work are those of the authors, and do not reflect the official policy or position of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Veterans Affairs, Department of Defense, or the US Government. Approved for public release; distribution is unlimited. Human subjects participated in this study after giving their free and informed consent. This research has been conducted in compliance with all applicable federal regulations governing the protection of human subjects in research. NR 67 TC 34 Z9 36 U1 1 U2 14 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUL 1 PY 2013 VL 36 IS 7 BP 1009 EP 1018 DI 10.5665/sleep.2798 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 172XG UT WOS:000321039500010 ER PT J AU Kounou, KB Bui, E Dassa, KS Hinton, D Fischer, L Djassoa, G Birmes, P Schmitt, L AF Kounou, Kossi B. Bui, Eric Dassa, Kolou S. Hinton, Devon Fischer, Laura Djassoa, Gnansa Birmes, Philippe Schmitt, Laurent TI Childhood trauma, personality disorders symptoms and current major depressive disorder in Togo SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Childhood trauma; Personality disorders; Depression; Sub-Saharan Africa; Togo ID SEXUAL-ABUSE; RISK-FACTORS; LIFE EVENTS; ADULT PSYCHOPATHOLOGY; NEGLECTED CHILDREN; ADVERSITIES; HEALTH; MALTREATMENT; PREVALENCE; SAMPLE AB Childhood trauma (CT) has been found to be associated with major depressive disorder (MDD) and personality disorders (PD) in adulthood in Western countries, but little is known about the relationship between CT, PD and MDD in sub-Saharan Africa. The present study aims to examine: (1) the frequency of the CT, (2) the association between CT, PD symptoms and MDD and (3) the mediating role of PD between CT and MDD in Togo. One hundred and eighty-one participants (91 individuals with current MDD and 90 healthy controls without psychiatric history) completed the 28-item CT Questionnaire (CTQ) and the Personality Diagnostic Questionnaire (PDQ-4+). Participants in the MDD group reported more frequently emotional, sexual and physical abuse and emotional and physical neglect than controls (p < 0.001). There was a significant positive correlation between the total abuse and the PDQ-4 + score (r = 0.48, p < 0.01) in the total sample. Emotional and sexual abuses were associated with current MDD and the number of PD criteria endorsed. Furthermore, PD symptoms mediated partially the relationship between CT and current MDD. Our results suggest an association between CT and current MDD in French-speaking sub-Saharan Africa, and that this relationship may be explained by PD symptoms. Prospective studies to confirm these results are warranted. C1 [Kounou, Kossi B.; Bui, Eric; Birmes, Philippe; Schmitt, Laurent] Univ Toulouse, Hop Casselardit, CHU Toulouse, UPS,LST,EA 4560, F-31059 Toulouse 9, France. [Kounou, Kossi B.; Dassa, Kolou S.; Djassoa, Gnansa] Univ Lome, Psychol Lab, Lome, Togo. [Bui, Eric; Hinton, Devon; Fischer, Laura] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric; Hinton, Devon] Harvard Univ, Sch Med, Boston, MA USA. RP Bui, E (reprint author), Univ Toulouse, Hop Casselardit, CHU Toulouse, UPS,LST,EA 4560, 170 Av Casselardit,TSA 40031, F-31059 Toulouse 9, France. EM tebui@partners.org RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Agence Universitaire de la Francophonie; CHU de Toulouse FX K. B. Kounou has received a Ph.D. Grant from "Agence Universitaire de la Francophonie" within the Framework of this research. E. Bui was supported by a fellowship from the CHU de Toulouse. We thank Emefa Kwadzo for her translation assistance. NR 43 TC 4 Z9 4 U1 1 U2 13 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JUL PY 2013 VL 48 IS 7 BP 1095 EP 1103 DI 10.1007/s00127-012-0634-2 PG 9 WC Psychiatry SC Psychiatry GA 171TY UT WOS:000320953500008 PM 23224674 ER PT J AU Keske, RR Rees, VW Behm, I Wadler, BM Geller, AC AF Keske, Robyn R. Rees, Vaughan W. Behm, Ilan Wadler, Brianna M. Geller, Alan C. TI Second-hand smoke exposure and mitigation strategies among home visitation workers SO TOBACCO CONTROL LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; SECONDHAND SMOKE; BAR WORKERS; RESPIRATORY HEALTH; UNITED-STATES; AIR-QUALITY; FREE LAWS; IMPACT; NICOTINE AB Objectives Protection of workers from second-hand smoke (SHS) in occupational settings is an important policy priority, yet little attention has been given to SHS protection for home visitation health workers, who number almost 2 million in the USA. Self-reported SHS exposure, SHS mitigation strategies and suggestions for further SHS exposure reduction approaches were obtained from home visitation health workers in Massachusetts. Methods A cross-sectional survey was conducted among Massachusetts Early Intervention workers (N=316) at their state-wide conference in April 2010. Results Eighty-three per cent of respondents reported at least 1 hour per month of SHS exposure, and 16% reported at least 11 hours per month. Nevertheless, only 22% of workers counselled clients on maintaining a smoke-free home. Fewer than 30% of workers had ever voiced concerns to their employing agency, and just 12% had raised their concerns directly with clients. Only 14% stated that their agency had rules designed to protect workers from SHS. Conclusions SHS exposure occurs frequently among home visitation health workers. The data point to a substantial population who are not protected from SHS exposure by formal policies. C1 [Keske, Robyn R.; Rees, Vaughan W.; Behm, Ilan] Harvard Univ, Ctr Global Tobacco Control, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Wadler, Brianna M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Rees, VW (reprint author), Harvard Univ, Ctr Global Tobacco Control, Sch Publ Hlth, Landmark Bldg,Level 3 East,677 Huntington Ave, Boston, MA 02115 USA. EM vrees@hsph.harvard.edu FU National Institutes of Health/National Institute on Minority Health and Health Disparities [R24-MD-002772] FX This study was supported by National Institutes of Health/National Institute on Minority Health and Health Disparities, grant R24-MD-002772. NR 33 TC 0 Z9 0 U1 1 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD JUL PY 2013 VL 22 IS 4 BP 250 EP 254 DI 10.1136/tobaccocontrol-2011-050133 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 161AR UT WOS:000320163000020 PM 22184207 ER PT J AU Khazim, K Giustarini, D Rossi, R Verkaik, D Cornell, JE Cunningham, SED Mohammad, M Trochta, K Lorenzo, C Folli, F Bansal, S Fanti, P AF Khazim, Khaled Giustarini, Daniela Rossi, Ranieri Verkaik, Darlene Cornell, John E. Cunningham, Sue E. D. Mohammad, Maryam Trochta, Kara Lorenzo, Carlos Folli, Franco Bansal, Shweta Fanti, Paolo TI Glutathione redox potential is low and glutathionylated and cysteinylated hemoglobin levels are elevated in maintenance hemodialysis patients SO TRANSLATIONAL RESEARCH LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; CHRONIC KIDNEY-DISEASE; OXIDATIVE STRESS; LIQUID-CHROMATOGRAPHY; RESPIRATORY BURST; CATION CHANNELS; S-THIOLATION; HUMAN PLASMA; BLOOD; ERYTHROCYTES AB Glutathione (GSH), the most abundant intracellular low molecular mass thiol, protects cells from oxidative damage and regulates their function. Available information is inconsistent regarding levels of GSH and its disulfide (GSSG) in maintenance hemodialysis patients (HD). In addition, very limited data are available in HD about the relationship of GSH and GSSG with other measures of thiol metabolism and with the clinical profile. We tested the hypothesis that erythrocyte GSH/GSSG redox potential (Eh) is lower in HD than in healthy controls (C), and that Eh correlates with posttranslational thiolation of hemoglobin (Hb) and with standard clinical parameters in HD. In cross-sectional comparison of 33 stable HD and 21 C, we found a net loss of reducing capacity in HD as indicated by low erythrocyte GSH/GSSG Eh (-257 +/- 5.5 vs -270 +/- 5.6 mV, P = 0.002). Glutathionylated Hb (HbSSG) was 46% higher in HD than C (19.3 +/- 4.80 vs 13.2 +/- 2.79 pmol/mg Hb; P = 0.001) and cysteinylated Hb (HbSSCy) was >3-fold higher in HD than C (38.3 (29.0-63.3) vs 11.5 (9.6-17.2) pmol/mg Hb; P = 0.001). In multiple regression analysis of the HD cases, statistically significant associations were found between the GSH/GSSG Et, and the blood urea nitrogen (P = 0.001), creatinine (P = 0.015) and normalized protein catabolic rate (P = 0.05), after adjusting for age, race/ethnicity, and etiology of end-stage renal disease. In conclusion, accurate and precise analysis of GSH, GSSG, and mixed disulfides reveals loss of erythrocyte GSH/GSSG Eh, rise of both HbSSG and HbSSCy, and correlation of these thiols with measures of uremia and dietary protein intake. C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, Sch Med, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Sch Hlth Profess, Program Dietet & Nutr, San Antonio, TX 78229 USA. Audie L Murphy Vet Mem Hosp, San Antonio, TX USA. Western Galilee Hosp, Div Nephrol, Nahariyya, Israel. Univ Siena, Lab Pharmacol & Toxicol, Dept Life Sci, I-53100 Siena, Italy. RP Fanti, P (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol MC 7882, San Antonio, TX 78229 USA. EM fanti@uthscsa.edu OI Giustarini, Daniela/0000-0003-4929-5316; folli, franco/0000-0001-9824-5222 FU NIH-NCCAM [AT004490]; VA [1I01CX000264] FX This work was supported by grants (to P.F.) from NIH-NCCAM (#AT004490) and from the VA (Merit Review #1I01CX000264). NR 45 TC 8 Z9 8 U1 1 U2 7 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 JUL PY 2013 VL 162 IS 1 BP 16 EP 25 DI 10.1016/j.trsl.2012.12.014 PG 10 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 173OU UT WOS:000321089600002 PM 23333585 ER PT J AU Li, XB Hartwell, KJ Borckardt, J Prisciandaro, JJ Saladin, ME Morgan, PS Johnson, KA LeMatty, T Brady, KT George, MS AF Li, Xingbao Hartwell, Karen J. Borckardt, Jeffery Prisciandaro, James J. Saladin, Michael E. Morgan, Paul S. Johnson, Kevin A. LeMatty, Todd Brady, Kathleen T. George, Mark S. TI Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: a preliminary real-time fMRI study SO ADDICTION BIOLOGY LA English DT Article DE anterior cingulate cortex; cue-induced craving; neurofeedback; nicotine dependence; real-time fMRI; smoking cessation ID RESTING TOBACCO SMOKERS; NICOTINE DEPENDENCE; BRAIN ACTIVATION; DRUG-ADDICTION; FRONTAL GYRUS; ABSTINENCE; TASK; NEUROFEEDBACK; EXPECTANCY; RESPONSES AB Numerous research groups are now using analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in real time'. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real-time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a reduce craving' paradigm, participants were instructed to reduce' their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate increase resistance' paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the reduce craving' task (P=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the reduce craving' session (P=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the increase resistance' session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence. C1 [Li, Xingbao; Hartwell, Karen J.; Borckardt, Jeffery; Prisciandaro, James J.; Saladin, Michael E.; LeMatty, Todd; Brady, Kathleen T.; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.; George, Mark S.] Ralph H Johnson VA Med Ctr, Dept Psychiat, Charleston, SC USA. [Morgan, Paul S.] Univ Nottingham, Dept Acad Radiol, Nottingham NG7 2RD, England. [Johnson, Kevin A.] Standford Univ, Syst Neurosci & Pain Lab, Dept Anesthesiol, Palo Alto, CA USA. RP Li, XB (reprint author), MUSC IOP, Dept Psychiat, 502 N,67 President St, Charleston, SC 29425 USA. EM lixi@musc.edu OI Morgan, Paul/0000-0002-5870-1446 FU National Institute of Health [5R21DA026085]; Brainsway; Cyberonics; Force Protection; GlaxoSmithKline; Jazz Pharmaceuticals; MECTA; Neurospace; PureTech Ventures FX This study is supported by National Institute of Health Grant no. 5R21DA026085 (KTB, MSG).; Mark George has served as a paid consultant to or received research support from Brainsway, Cyberonics, Force Protection, GlaxoSmithKline, Jazz Pharmaceuticals, MECTA, Neurospace, and PureTech Ventures and as an unpaid consultant to Brainsonix, Brainsway, Cephos, MECTA, NeoSync, and Neuronetics. The Medical University of South Carolina has two patent applications in Dr. George's name on combining TMS with MRI imaging. NR 46 TC 44 Z9 46 U1 2 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JUL PY 2013 VL 18 IS 4 BP 739 EP 748 DI 10.1111/j.1369-1600.2012.00449.x PG 10 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 169IW UT WOS:000320774700016 PM 22458676 ER PT J AU Stirman, SW Gutierrez-Colina, A Toder, K Esposito, G Barg, F Castro, F Beck, AT Crits-Christoph, P AF Stirman, Shannon Wiltsey Gutierrez-Colina, Ana Toder, Katherine Esposito, Gregory Barg, Frances Castro, Frank Beck, Aaron T. Crits-Christoph, Paul TI Clinicians' Perspectives on Cognitive Therapy in Community Mental Health Settings: Implications for Training and Implementation SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Evidence-based psychosocial treatments; Cognitive therapy; Dissemination and implementation ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; BEHAVIORAL THERAPY; ORGANIZATIONAL CULTURE; STAFF TURNOVER; ATTITUDES; INTERVENTIONS; SERVICES; PROGRAMS; DISSEMINATION AB Policymakers are investing significant resources in large-scale training and implementation programs for evidence-based psychological treatments (EBPTs) in public mental health systems. However, relatively little research has been conducted to understand factors that may influence the success of efforts to implement EBPTs for adult consumers of mental health services. In a formative investigation during the development of a program to implement cognitive therapy (CT) in a community mental health system, we surveyed and interviewed clinicians and clinical administrators to identify potential influences on CT implementation within their agencies. Four primary themes were identified. Two related to attitudes towards CT: (1) ability to address client needs and issues that are perceived as most central to their presenting problems, and (2) reluctance to fully implement CT. Two themes were relevant to context: (1) agency-level barriers, specifically workload and productivity concerns and reactions to change, and (2) agency-level facilitators, specifically, treatment planning requirements and openness to training. These findings provide information that can be used to develop strategies to facilitate the implementation of CT interventions for clients being treated in public-sector settings. C1 [Stirman, Shannon Wiltsey; Castro, Frank] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Stirman, Shannon Wiltsey; Castro, Frank] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Gutierrez-Colina, Ana] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Toder, Katherine; Beck, Aaron T.; Crits-Christoph, Paul] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Esposito, Gregory] Univ Penn, Philadelphia, PA 19104 USA. [Castro, Frank] Univ Penn, Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Barg, Frances] Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. RP Stirman, SW (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B3, Boston, MA 02130 USA. EM sws@bu.edu FU NIMH NIH HHS [R25 MH080916-01A2, K99 MH080100, K99-MH080100, P20 MH071905, P20 MH71905, R00 MH080100, R24 MH070698, R24MH070698, R25 MH080916, T32 MH019836, T32MH019836] NR 64 TC 9 Z9 9 U1 6 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 2013 VL 40 IS 4 BP 274 EP 285 DI 10.1007/s10488-012-0418-8 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 163LU UT WOS:000320338600004 PM 22426739 ER PT J AU Shiner, B D'Avolio, LW Nguyen, TM Zayed, MH Young-Xu, YN Desai, RA Schnurr, PP Fiore, LD Watts, BV AF Shiner, Brian D'Avolio, Leonard W. Nguyen, Thien M. Zayed, Maha H. Young-Xu, Yinong Desai, Rani A. Schnurr, Paula P. Fiore, Louis D. Watts, Bradley V. TI Measuring Use of Evidence Based Psychotherapy for Posttraumatic Stress Disorder SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Psychotherapy; Evidence-based medicine; Posttraumatic stress disorder; Natural language processing; Health services utilization ID OF-VETERANS-AFFAIRS; COGNITIVE PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; STATISTICAL PROCESS-CONTROL; MENTAL-HEALTH; EXPOSURE THERAPY; PTSD; AFGHANISTAN; IRAQ; REDUCE AB To improve methods of estimating use of evidence-based psychotherapy for posttraumatic stress disorder in the Veteran's health administration, we evaluated administrative data and note text for patients newly enrolling in six VHA outpatient PTSD clinics in New England during the 2010 fiscal year (n = 1,924). Using natural language processing, we developed machine learning algorithms that mimic human raters in classifying note text. We met our targets for algorithm performance as measured by precision, recall, and F-measure. We found that 6.3 % of our study population received at least one session of evidence-based psychotherapy during the initial 6 months of treatment. Evidence-based psychotherapies appear to be infrequently utilized in VHA outpatient PTSD clinics in New England. Our method could support efforts to improve use of these treatments. C1 [Shiner, Brian; Zayed, Maha H.; Watts, Bradley V.] VA Med Ctr, White River Jct, VT USA. [Shiner, Brian; Watts, Bradley V.] VA New England Vet Engn Resource Ctr, White River Jct, VT USA. [Shiner, Brian; Desai, Rani A.; Schnurr, Paula P.] VA Natl Ctr PTSD, White River Jct, VT USA. [Shiner, Brian; Young-Xu, Yinong; Schnurr, Paula P.; Watts, Bradley V.] Geisel Sch Med Dartmouth, Hanover, NH USA. [D'Avolio, Leonard W.; Nguyen, Thien M.; Fiore, Louis D.] VA Boston Hlth Care Syst, Jamaica Plain, MA USA. [D'Avolio, Leonard W.; Nguyen, Thien M.; Fiore, Louis D.] Massachusetts Vet Epidemiol & Informat Ctr, Jamaica Plain, MA USA. [D'Avolio, Leonard W.] Harvard Univ, Sch Med, Boston, MA USA. [Desai, Rani A.] VA Northeast Program Evaluat Ctr, West Haven, CT USA. [Desai, Rani A.] Yale Univ, Sch Med, New Haven, CT USA. [Desai, Rani A.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Fiore, Louis D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Fiore, Louis D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Shiner, B (reprint author), VA Med Ctr, White River Jct, VT USA. EM brian.shiner@va.gov NR 35 TC 37 Z9 37 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 2013 VL 40 IS 4 BP 311 EP 318 DI 10.1007/s10488-012-0421-0 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 163LU UT WOS:000320338600007 PM 22535469 ER PT J AU Van der Elst, EM Mbogua, J Operario, D Mutua, G Kuo, C Mugo, P Kanungi, J Singh, S Haberer, J Priddy, F Sanders, EJ AF Van der Elst, Elisabeth Maria Mbogua, Judie Operario, Don Mutua, Gaudensia Kuo, Caroline Mugo, Peter Kanungi, Jennifer Singh, Sagri Haberer, Jessica Priddy, Frances Sanders, Eduard Joachim TI High Acceptability of HIV Pre-exposure Prophylaxis but Challenges in Adherence and Use: Qualitative Insights from a Phase I Trial of Intermittent and Daily PrEP in At-Risk Populations in Kenya SO AIDS AND BEHAVIOR LA English DT Article DE Men who have sex with men; HIV pre-exposure prophylaxis; PrEP; Adherence; Kenya ID MEN; SEX; INFECTION AB This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness. C1 [Van der Elst, Elisabeth Maria; Mugo, Peter; Kanungi, Jennifer; Sanders, Eduard Joachim] Kenya Govt Med Res Ctr, Ctr Geog Med Res Coast, Kilifi, Kenya. [Mbogua, Judie] Int AIDS Vaccine Initiat, Nairobi, Kenya. [Operario, Don; Kuo, Caroline] Brown Univ, Providence, RI 02912 USA. [Mutua, Gaudensia] Kenya AIDS Vaccine Initiat, Nairobi, Kenya. [Kuo, Caroline] Rhode Isl Hosp, Providence, RI USA. [Singh, Sagri; Priddy, Frances] Int AIDS Vaccine Initiat, New York, NY USA. [Haberer, Jessica] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Sanders, Eduard Joachim] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. RP Van der Elst, EM (reprint author), Kenya Govt Med Res Ctr, Ctr Geog Med Res Coast, POB 230, Kilifi, Kenya. EM EvanderElst@kemri-wellcome.org FU NIMH NIH HHS [K23 MH087228]; Wellcome Trust [092654] NR 22 TC 28 Z9 28 U1 0 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD JUL PY 2013 VL 17 IS 6 BP 2162 EP 2172 DI 10.1007/s10461-012-0317-8 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 158RS UT WOS:000319990900024 PM 23080358 ER PT J AU Schumm, JA Fredman, SJ Monson, CM Chard, KM AF Schumm, Jeremiah A. Fredman, Steffany J. Monson, Candice M. Chard, Kathleen M. TI Cognitive-Behavioral Conjoint Therapy for PTSD: Initial Findings for Operations Enduring and Iraqi Freedom Male Combat Veterans and Their Partners SO AMERICAN JOURNAL OF FAMILY THERAPY LA English DT Article ID SYMPTOMS AB Posttraumatic stress disorder (PTSD) and partner relationship difficulties commonly co-occur among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF-OIF). This study reports upon results for six male OEF-OIF Veterans with PTSD and their female relationship partners who completed cognitive-behavioral conjoint therapy for PTSD (CBCT for PTSD), which is a treatment that targets reductions in PTSD and couple distress. Case- and group-level data supported reductions in Veterans' PTSD symptoms and female partners' relationship distress. These findings suggest that CBCT for PTSD may be a promising intervention for OEF-OIF Veterans' PTSD and their partners. C1 [Schumm, Jeremiah A.; Chard, Kathleen M.] Cincinnati VA Med Ctr, Cincinnati, OH USA. [Schumm, Jeremiah A.; Chard, Kathleen M.] Univ Cincinnati, Cincinnati, OH USA. [Fredman, Steffany J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fredman, Steffany J.] Harvard Univ, Sch Med, Boston, MA USA. [Monson, Candice M.] Ryerson Univ, Toronto, ON, Canada. RP Schumm, JA (reprint author), Cincinnati VA Med Ctr, PTSD & Anxiety Disorders Div 116B1, 1000 S Ft Thomas Ave, Ft Thomas, KY 41075 USA. EM jeremiah.schumm@va.gov NR 19 TC 12 Z9 12 U1 0 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0192-6187 J9 AM J FAM THER JI Am. J. Fam. Ther. PD JUL 1 PY 2013 VL 41 IS 4 BP 277 EP 287 DI 10.1080/01926187.2012.701592 PG 11 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 168FO UT WOS:000320691300001 ER PT J AU Shaaya, EA Hirshberg, JS Rabe, OT Thibert, RL Inglessis, I Sharma, A Thiele, EA AF Shaaya, Elias A. Hirshberg, Jacqueline S. Rabe, Olivia T. Thibert, Ronald L. Inglessis, Ignacio Sharma, Amita Thiele, Elizabeth A. TI Cardiac fat-containing lesions are common in tuberous sclerosis complex SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE cardiac angiomyolipoma; cardiac fat lesions; cardiac fat-containing lesion; tuberous sclerosis complex ID CONSENSUS CONFERENCE; RHABDOMYOMA; TUMORS AB Tuberous sclerosis complex (TSC) is a highly variable, multisystem, genetic disorder that affects approximately 1:6,000 individuals. It has previously been thought that the cardiac manifestation of TSC is congenital rhabdomyomas, which occur during infancy and typically regress during childhood. Recently, there have been findings of cardiac fat-containing lesions in adult TSC patients that appear distinct from the presence of cardiac rhabdomyomas. We review the chest CT scans of 73 individuals with TSC to check for cardiac fat-containing lesions. Fat-containing lesions were found in the heart of approximately one-third of adolescents and adults with TSC. In this population with cardiac fat-containing lesions, no statistically significant difference was observed between the genders and between the different mutation types. Compared to those without cardiac fat findings, those with cardiac fat were more than twice as likely to have another abdominal manifestation of TSC. The results indicate that it may be appropriate to consider these cardiac fat foci as a clinical criterion for the diagnosis of TSC, given their frequency in our population. Our findings also suggest that a relation exists between the cardiac fat-containing lesions and other abdominal angiomyolipomas. More research regarding these cardiac fat-containing lesions is needed to better characterize their origin and clinical significance. (c) 2013 Wiley Periodicals, Inc. C1 [Shaaya, Elias A.; Hirshberg, Jacqueline S.; Rabe, Olivia T.; Thibert, Ronald L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Inglessis, Ignacio] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279] FX Grant sponsor: Herscot Center for Tuberous Sclerosis Complex; Grant sponsor: NIH/NINDS; Grant number: P01 NS024279. NR 21 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL PY 2013 VL 161A IS 7 BP 1662 EP 1665 DI 10.1002/ajmg.a.36037 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 167RF UT WOS:000320650100018 PM 23703751 ER PT J AU Xu, H Zhang, T Man, GCW May, KE Becker, CM Davis, TN Kung, AL Birsner, AE D'Amato, RJ Wong, AWY Wang, CC AF Xu, Hui Zhang, Tao Man, Gene Chi Wai May, Katie E. Becker, Christian M. Davis, Tina N. Kung, Andrew L. Birsner, Amy E. D'Amato, Robert J. Wong, Alice Wai Yee Wang, Chi Chiu TI Vascular endothelial growth factor C is increased in endometrium and promotes endothelial functions, vascular permeability and angiogenesis and growth of endometriosis SO ANGIOGENESIS LA English DT Article DE Endometriosis; Angiogenesis; Vascular endothelial growth factor; VEGF-C ID MOUSE MODEL; VEGF-C; PERITONEAL ENDOMETRIOSIS; IN-VITRO; EXPRESSION; CELLS; THALIDOMIDE; ACTIVATION; MECHANISMS; INHIBITORS AB Endometriosis is an angiogenesis-dependent disease. Many studies demonstrated inhibition of angiogenesis leads to inhibition of endometriotic growth, however underlying mechanism is still not fully understood. Our previous study suggested vascular endothelial growth factor C (VEGF-C) as a target of anti-angiogenesis therapy for endometriosis. In this study, VEGF-C in endometrium and its role in angiogenesis of endometriosis were studied. Human endometrium were obtained from women with and without endometriosis for molecular studies. VEGF-A, VEGF-B, VEGF-C and VEGF-D mRNA and proteins in eutopic and ectopic endometrium were measured. Human endothelial cells were transfected with VEGF-C siRNA in vitro, effects of VEGF-C on endothelial cell migration, invasion and tube formation were investigated in vitro. Angiogenesis was inhibited in wild type mice, vascular permeability in dermal skin was determined in vivo. Transplanted endometrium were inhibited by VEGF-C siRNA in immunocompromised mice, development, growth and angiogenesis of the experimental endometriosis were compared in vivo. The results showed that VEGF-C mRNA and protein were increased in eutopic and ectopic endometrium of endometriosis patients. VEGF-C siRNA significantly inhibited endothelial cell migration and tube formation. VEGF-C siRNA significantly inhibited development and angiogenesis of the experimental endometriotic lesions in mice. Supplementation and over-expression of VEGF-C significantly reversed the inhibitory effects on the endothelial functions, vascular permeability and endometriotic growth. In conclusion, VEGF-C is increased in endometrium and it promotes endothelial functions, vascular permeability and development of experimental endometriosis. VEGF-C is important for angiogenesis in endometriosis. C1 [Xu, Hui; Zhang, Tao; Man, Gene Chi Wai; Wong, Alice Wai Yee; Wang, Chi Chiu] Chinese Univ Hong Kong, Dept Obstet & Gynaecol, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. [May, Katie E.; Becker, Christian M.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England. [Davis, Tina N.; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Davis, Tina N.; Kung, Andrew L.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Birsner, Amy E.; D'Amato, Robert J.] Harvard Univ, Childrens Hosp, Vasc Biol Program, Dept Surg,Med Sch, Boston, MA 02115 USA. [Wang, Chi Chiu] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. RP Wang, CC (reprint author), Chinese Univ Hong Kong, Dept Obstet & Gynaecol, Prince Wales Hosp, 1st Floor,Block E, Shatin, Hong Kong, Peoples R China. EM ccwang@cuhk.edu.hk RI Wang, Ronald/C-6541-2014; OI Kung, Andrew/0000-0002-9091-488X; Man, Chi Wai/0000-0002-8608-9688 FU Global Scholarship Programme for Research Excellence-CNOOC grant from the Chinese University of Hong Kong; Obstetrical and Gynaecological Society of Hong Kong; Hong Kong Research Grants Council [CUHK475012]; MRC [G0601458]; Oxford Partnership Comprehensive Biomedical Research Centre from the Department of Health's NIHR Biomedical Research Centres scheme; MRC Doctoral Training Account (DTA); Oxfordshire Health Services Research Committee Grant FX Special thanks to Muna El-Kasti, Elizabeth Rapa and Dionne Tanetta for assistance with the culture experiments. This work was supported by the Global Scholarship Programme for Research Excellence-CNOOC grant 2008-2009 from the Chinese University of Hong Kong to H. X. and C. C. W. to conduct experiments at Harvard and Oxford Universities; an Incentive Scheme on Research Performance from the Chinese University of Hong Kong to T.Z. for PhD study; a Hong Kong Obstetrical and Gynaecological Trust Fund 2010 grant from the Obstetrical and Gynaecological Society of Hong Kong to C. C. W. and G. C. W. G.; a General Research Fund 2012/2013 (CUHK475012) from Hong Kong Research Grants Council to C. C. W, C. M. B. and A. L. K.; a MRC New Investigator Award (G0601458) and the Oxford Partnership Comprehensive Biomedical Research Centre from the Department of Health's NIHR Biomedical Research Centres scheme to C. M. B.; a MRC Doctoral Training Account (DTA) and an Oxfordshire Health Services Research Committee Grant to K.E.M. NR 45 TC 14 Z9 17 U1 0 U2 21 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JUL PY 2013 VL 16 IS 3 BP 541 EP 551 DI 10.1007/s10456-013-9333-1 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 165EF UT WOS:000320465200005 PM 23334337 ER PT J AU Zeinali-Davarani, S Chow, MJ Turcotte, R Zhang, YH AF Zeinali-Davarani, Shahrokh Chow, Ming-Jay Turcotte, Raphael Zhang, Yanhang TI Characterization of Biaxial Mechanical Behavior of Porcine Aorta under Gradual Elastin Degradation SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Aneurysms; Elastin degradation; Vascular mechanics; Recruitment distribution function; Multiphoton microscopy; Collagen waviness ID COLLAGEN FIBER ORIENTATIONS; HUMAN ABDOMINAL-AORTA; MARFAN-SYNDROME; WALL MECHANICS; BIOLOGICAL-MATERIALS; CONSTITUTIVE MODEL; ARTERIAL-WALL; ANEURYSMS; TISSUES; AGE AB Arteries are composed of multiple constituents that endow the wall with proper structure and function. Many vascular diseases are associated with prominent mechanical and biological alterations in the wall constituents. In this study, planar biaxial tensile test data of elastase-treated porcine aortic tissue (Chow et al. in Biomech Model Mechanobiol 2013) is re-examined to characterize the altered mechanical behavior at multiple stages of digestion through constitutive modeling. Exponential-based as well as recruitment-based strain energy functions are employed and the associated constitutive parameters for individual digestion stages are identified using nonlinear parameter estimation. It is shown that when the major portion of elastin is degraded from a cut-open artery in the load-free state, the embedded collagen fibers are recruited at lower stretch levels under biaxial loads, leading to a rapid stiffening behavior of the tissue. Multiphoton microscopy illustrates that the collagen waviness decreases significantly with the degradation time, resulting in a rapid recruitment when the tissue is loaded. It is concluded that even when residual stresses are released, there exists an intrinsic mechanical interaction between arterial elastin and collagen that determines the mechanics of arteries and carries important implications to vascular mechanobiology. C1 [Zeinali-Davarani, Shahrokh; Chow, Ming-Jay; Zhang, Yanhang] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Turcotte, Raphael; Zhang, Yanhang] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Turcotte, Raphael] Harvard Univ, Sch Med, Adv Microscopy Program, Ctr Syst Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turcotte, Raphael] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zhang, YH (reprint author), Boston Univ, Dept Mech Engn, 110 Cummington Mall, Boston, MA 02215 USA. EM yanhang@bu.edu FU National Heart, Lung, and Blood Institute [HL-098028]; National Science Foundation [CMMI 1100791, CAREER 0954825] FX This work has been supported in part by the National Heart, Lung, and Blood Institute Grant HL-098028 and National Science Foundation grants CMMI 1100791 and CAREER 0954825. Authors would like to thank Prof. Charles P. Lin from the Wellman Center for Photomedicine for providing access to the multiphoton microscope. NR 60 TC 21 Z9 21 U1 2 U2 33 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUL PY 2013 VL 41 IS 7 BP 1528 EP 1538 DI 10.1007/s10439-012-0733-y PG 11 WC Engineering, Biomedical SC Engineering GA 163IJ UT WOS:000320329200016 PM 23297000 ER PT J AU Kulig, KM Luo, X Finkelstein, EB Liu, XH Goldman, SM Sundback, CA Vacanti, JP Neville, CM AF Kulig, Katherine M. Luo, Xiao Finkelstein, Eric B. Liu, Xiang-Hong Goldman, Scott M. Sundback, Cathryn A. Vacanti, Joseph P. Neville, Craig M. TI Biologic properties of surgical scaffold materials derived from dermal ECM SO BIOMATERIALS LA English DT Article DE Collagen; Extracellular matrix (ECM); Bioactivity; Scaffold; Chemotaxis; Decellularization ID SMALL-INTESTINAL SUBMUCOSA; PORCINE URINARY-BLADDER; EXTRACELLULAR-MATRIX; IN-VITRO; MACROPHAGE PHENOTYPE; COLLAGEN PERMACOL; ACELLULAR MATRIX; IMMUNE-RESPONSE; HERNIA REPAIR; CHEST-WALL AB Surgical scaffold materials manufactured from donor human or animal tissue are increasingly being used to promote soft tissue repair and regeneration. The clinical product consists of the residual extracellular matrix remaining after a rigorous decellularization process. Optimally, the material provides both structural support during the repair period and cell guidance cues for effective incorporation into the regenerating tissue. Surgical scaffold materials are available from several companies and are unique products manufactured by proprietary methodology. A significant need exists for a more thorough understanding of scaffold properties that impact the early steps of host cell recruitment and infiltration. In this study, a panel of in vitro assays was used to make direct comparisons of several similar, commercially-available materials: Alloderm, Medeor Matrix, Permacol, and Strattice. Differences in the materials were detected for both cell signaling and scaffold architecture-dependent cell invasion. Material-conditioned media studies found Medeor Matrix to have the greatest positive effect upon cell proliferation and induction of migration. Strattice provided the greatest chemotaxis signaling and best suppressed apoptotic induction. Among assays measuring structure-dependent properties, Medeor Matrix was superior for cell attachment, followed by Permacol. Only Alloderm and Medeor Matrix supported chemotaxis-driven cell invasion beyond the most superficial zone. Medeor Matrix was the only material in the chorioallantoic membrane assay to support substantial cell invasion. These results indicate that both biologic and structural properties need to be carefully assessed in the considerable ongoing efforts to develop new uses and products in this important class of biomaterials. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Kulig, Katherine M.; Luo, Xiao; Finkelstein, Eric B.; Sundback, Cathryn A.; Vacanti, Joseph P.; Neville, Craig M.] Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Surg, Boston, MA 02114 USA. [Luo, Xiao] Huazhong Univ Sci & Technol, Tongji Hosp, Wuhan 430074, Peoples R China. [Finkelstein, Eric B.; Sundback, Cathryn A.; Vacanti, Joseph P.; Neville, Craig M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, Xiang-Hong; Goldman, Scott M.] Kensey Nash Corp, Exton, PA 19341 USA. RP Neville, CM (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN-4809, Boston, MA 02114 USA. EM neville@helix.mgh.harvard.edu FU China Scholarship Council FX We thank Chris Bowley for help in reviewing the protocols. Xiao Luo, M.D. was the recipient of a national scholarship from the China Scholarship Council. NR 50 TC 10 Z9 10 U1 7 U2 35 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUL PY 2013 VL 34 IS 23 BP 5776 EP 5784 DI 10.1016/j.biomaterials.2013.02.055 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 161UW UT WOS:000320219800005 PM 23642537 ER PT J AU Dang, TT Thai, AV Cohen, J Slosberg, JE Siniakowicz, K Doloff, JC Ma, ML Hollister-Lock, J Tang, KM Gu, Z Cheng, H Weir, GC Langer, R Anderson, DG AF Dang, Tram T. Thai, Anh V. Cohen, Joshua Slosberg, Jeremy E. Siniakowicz, Karolina Doloff, Joshua C. Ma, Minglin Hollister-Lock, Jennifer Tang, Katherine M. Gu, Zhen Cheng, Hao Weir, Gordon C. Langer, Robert Anderson, Daniel G. TI Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug SO BIOMATERIALS LA English DT Article DE Anti-inflammatory drugs; Curcumin; Encapsulated islets; Diabetes; Fibrotic overgrowth; Host response ID INDUCED INSULIN-RESISTANCE; ALGINATE-PLL CAPSULES; NF-KAPPA-B; COMPOSITE MICROCAPSULES; CELL ENCAPSULATION; CONTROLLED-RELEASE; PANCREATIC-ISLETS; TISSUE-RESPONSE; NITRIC-OXIDE; IN-VITRO AB Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes. Published by Elsevier Ltd. C1 [Dang, Tram T.; Cheng, Hao; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Dang, Tram T.; Thai, Anh V.; Slosberg, Jeremy E.; Doloff, Joshua C.; Ma, Minglin; Tang, Katherine M.; Gu, Zhen; Cheng, Hao; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Dang, Tram T.; Thai, Anh V.; Slosberg, Jeremy E.; Doloff, Joshua C.; Ma, Minglin; Tang, Katherine M.; Gu, Zhen] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Cohen, Joshua; Siniakowicz, Karolina; Hollister-Lock, Jennifer; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Anderson, DG (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dgander@mit.edu RI Gu, Zhen/B-2312-2010; Dang, Tram/E-7966-2011 FU Juvenile Diabetes Research Foundation; Leona M and Harry B. Hemsley Charitabe Trust; National Institute of Heath [DE016516]; A*STAR National Science graduate fellowship from the Agency for Science, Technology and Research of Singapore; Tayebati Family Foundation FX We thank the staff of AML Laboratories (Baltimore, MD, USA) and MIT Division of Comparative Medicine for their assistance with processing of the histology samples. This work was supported by the Juvenile Diabetes Research Foundation, the Leona M and Harry B. Hemsley Charitabe Trust, and the National Institute of Heath (Grant DE016516). T.D was supported by the A*STAR National Science graduate fellowship from the Agency for Science, Technology and Research of Singapore. D.G.A. is further supported by a generous gift from the Tayebati Family Foundation. The authors declared no conflict of interest. NR 54 TC 23 Z9 23 U1 5 U2 87 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD JUL PY 2013 VL 34 IS 23 BP 5792 EP 5801 DI 10.1016/j.biomaterials.2013.04.016 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 161UW UT WOS:000320219800007 PM 23660251 ER PT J AU Zhou, YH Barry, WT Wright, FA AF Zhou, Yi-Hui Barry, William T. Wright, Fred A. TI Empirical pathway analysis, without permutation SO BIOSTATISTICS LA English DT Article DE Gene sets; Multiple hypothesis testing; Permutation approximation ID GENE-SET ANALYSIS; BREAST-CANCER; FUNCTIONAL CATEGORIES; TESTING ASSOCIATION; MICROARRAY DATA; EXPRESSION DATA; SURVIVAL AB Resampling-based expression pathway analysis techniques have been shown to preserve type I error rates, in contrast to simple gene-list approaches that implicitly assume the independence of genes in ranked lists. However, resampling is intensive in computation time and memory requirements. We describe accurate analytic approximations to permutations of score statistics, including novel approaches for Pearson's correlation, and summed score statistics, that have good performance for even relatively small sample sizes. Our approach preserves the essence of permutation pathway analysis, but with greatly reduced computation. Extensions for inclusion of covariates and censored data are described, and we test the performance of our procedures using simulations based on real datasets. These approaches have been implemented in the new R package safeExpress. C1 [Zhou, Yi-Hui; Wright, Fred A.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Barry, William T.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Zhou, YH (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM yihuiz@live.unc.edu FU Gillings Statistical Genomics Innovation Lab; EPA [RD83382501]; NCI [P01CA142538]; NIEHS [P30ES010126, P42ES005948] FX This work was supported in part by the Gillings Statistical Genomics Innovation Lab, EPA RD83382501, NCI P01CA142538, and NIEHS P30ES010126 and P42ES005948. NR 30 TC 12 Z9 12 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2013 VL 14 IS 3 BP 573 EP 585 DI 10.1093/biostatistics/kxt004 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 164TQ UT WOS:000320433000013 PM 23428933 ER PT J AU Smith, K James, JA Harley, JB AF Smith, Kenneth James, Judith A. Harley, John B. TI Editorial for Lindop et al. "Long-term Ro60 humoral autoimmunity in primary Sjogren's syndrome is maintained by rapid clonal turnover" SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTIBODY; CELLS C1 [Smith, Kenneth] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [James, Judith A.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Rheumatol, Cincinnati, OH 45229 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, CAGE, Cincinnati, OH 45229 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Harley, JB (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Rheumatol, Cincinnati, OH 45229 USA. EM Ken-Smith@omrf.org; Judith-James@omrf.org; John.Harley@cchmc.org NR 18 TC 2 Z9 2 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2013 VL 148 IS 1 BP 110 EP 112 DI 10.1016/j.clim.2013.04.015 PG 3 WC Immunology SC Immunology GA 164RN UT WOS:000320427300013 PM 23685220 ER PT J AU Gilman, SE AF Gilman, Stephen E. TI Commentary: The Causal and Nosological Status of Loss in Major Depression SO EPIDEMIOLOGY LA English DT Article ID BEREAVEMENT-RELATED DEPRESSION; RISK-FACTORS; DISORDER; EXCLUSION; ALCOHOL; ONSET; DECAY C1 [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 NR 22 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2013 VL 24 IS 4 BP 616 EP 618 DI 10.1097/EDE.0b013e3182953dcc PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 162ZU UT WOS:000320305900020 PM 23732737 ER PT J AU Hilbert, A Buerger, A Hartmann, AS Spenner, K Czaja, J Warschburger, P AF Hilbert, Anja Buerger, Arne Hartmann, Andrea S. Spenner, Kristina Czaja, Julia Warschburger, Petra TI Psychometric Evaluation of the Eating Disorder Examination Adapted for Children SO EUROPEAN EATING DISORDERS REVIEW LA English DT Article DE clinical interview; children and adolescents; eating disorders; psychometric properties ID ANOREXIA-NERVOSA; GERMAN VERSION; OBESE CHILDREN; ATTITUDES TEST; ADOLESCENTS; OVERWEIGHT; PSYCHOPATHOLOGY; RELIABILITY; PREVALENCE; YOUNGSTERS AB The Eating Disorder Examination adapted for children (ChEDE) is the child version of the semi-structured gold standard eating disorder interview for adults. This study was a comprehensive test statistic evaluation of the German ChEDE in a large sample of children and adolescents with anorexia nervosa, binge eating disorder, loss of control eating, overweight and obesity, as well as non-eating-disordered and chronically ill control probands (n=352). Excellent inter-rater reliability, adequate internal consistency and satisfactory stability of ChEDE indicators were demonstrated. ChEDE indicators discriminated between diverse forms of eating and weight disturbances and normative eating and were significantly correlated with conceptually related measures. Factorial validity was not convincing; a brief eight-item scale showed the best fit. Item statistics were mostly acceptable. Overall, the ChEDE's German translation reliably and validly assesses psychopathology across the eating and weight disorder spectrum and facilitates international comparison of eating disorder research. Copyright (c) 2013 John Wiley & Sons, Ltd and Eating Disorders Association. C1 [Hilbert, Anja] Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Dept Med Psychol & Med Sociol, Med Ctr, D-04109 Leipzig, Germany. [Buerger, Arne] Johannes Gutenberg Univ Mainz, D-55122 Mainz, Germany. [Hartmann, Andrea S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hartmann, Andrea S.] Harvard Univ, Sch Med, Boston, MA USA. [Spenner, Kristina] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. [Czaja, Julia] Univ Lubeck, Dept Psychosomat Med & Psychotherapy, Lubeck, Germany. [Warschburger, Petra] Univ Potsdam, Dept Psychol, Potsdam, Germany. RP Hilbert, A (reprint author), Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Dept Med Psychol & Med Sociol, Med Ctr, D-04109 Leipzig, Germany. EM anja.hilbert@medizin.uni-leipzig.de NR 54 TC 16 Z9 16 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1072-4133 J9 EUR EAT DISORD REV JI Eur. Eat. Disord. Rev. PD JUL PY 2013 VL 21 IS 4 BP 330 EP 339 DI 10.1002/erv.2221 PG 10 WC Psychology, Clinical SC Psychology GA 160JP UT WOS:000320116100008 PM 23456853 ER PT J AU Jiao, S Hsu, L Bezieau, S Brenner, H Chan, AT Chang-Claude, J Le Marchand, L Lemire, M Newcomb, PA Slattery, ML Peters, U AF Jiao, Shuo Hsu, Li Bezieau, Stephane Brenner, Hermann Chan, Andrew T. Chang-Claude, Jenny Le Marchand, Loic Lemire, Mathieu Newcomb, Polly A. Slattery, Martha L. Peters, Ulrike TI SBERIA: Set-Based Gene-Environment Interaction Test for Rare and Common Variants in Complex Diseases SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene-environment interaction; set based; correlation screening; GWAS; rare variants ID GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER RISK; TRAIT SIMILARITY REGRESSION; SUSCEPTIBILITY LOCI; SCORE TEST; BLADDER-CANCER; MULTIPLE GENES; POWERFUL; METAANALYSIS; SCAN AB Identification of gene-environment interaction (G x E) is important in understanding the etiology of complex diseases. However, partially due to the lack of power, there have been very few replicated G x E findings compared to the success in marginal association studies. The existing G x E testing methods mainly focus on improving the power for individual markers. In this paper, we took a different strategy and proposed a set-based gene-environment interaction test (SBERIA), which can improve the power by reducing the multiple testing burdens and aggregating signals within a set. The major challenge of the signal aggregation within a set is how to tell signals from noise and how to determine the direction of the signals. SBERIA takes advantage of the established correlation screening for G x E to guide the aggregation of genotypes within a marker set. The correlation screening has been shown to be an efficient way of selecting potential G x E candidate SNPs in case-control studies for complex diseases. Importantly, the correlation screening in case-control combined samples is independent of the interaction test. With this desirable feature, SBERIA maintains the correct type I error level and can be easily implemented in a regular logistic regression setting. We showed that SBERIA had higher power than benchmark methods in various simulation scenarios, both for common and rare variants. We also applied SBERIA to real genome-wide association studies (GWAS) data of 10,729 colorectal cancer cases and 13,328 controls and found evidence of interaction between the set of known colorectal cancer susceptibility loci and smoking. C1 [Jiao, Shuo; Hsu, Li; Newcomb, Polly A.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Bezieau, Stephane] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Newcomb, Polly A.; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. RP Jiao, S (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM sjiao@fhcrc.org RI Bezieau, stephane/G-5621-2015; Brenner, Hermann/B-4627-2017 OI Bezieau, stephane/0000-0003-0095-1319; Brenner, Hermann/0000-0002-6129-1572 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); National Institutes of Health [R01 CA60987, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, P50 CA 127003, CA42182, R37 CA54281, P01 CA033619, R01 CA63464, U01 CA074783, R01 CA076366, K05 CA154337]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Key Scientific and Technological Project [2011ZX09307-001-04]; National Basic Research Program, People's Republic of China [2011CB504303]; National meInstitutes of Health [R01 137178, P50 CA 127003, P01 CA 087969]; Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health, Genes, Environment and Health Initiative [NIH GEI] [Z01 CP 010200]; National Cancer Institute; NIH GEI [U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).; ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC).; COLO2&3: National Institutes of Health (R01 CA60987).; DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS: National Institutes of Health (R01 CA48998 to M. L. S).; Guangzhou-1: National Key Scientific and Technological Project 2011ZX09307-001-04 and the National Basic Research Program-2011CB504303, People's Republic of China.; HPFS is supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA 127003), NHS by the National meInstitutes of Health (R01 137178, P01 CA 087969, and P50 CA 127003), and PHS by the National Institutes of Health (CA42182).; MEC: National Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA63464).; OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section below. OFCCR is supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. Thomas J. Hudson and Brent W. Zanke are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Economic Development and Innovation.; PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer scan, supported by the Intramural Research Program of the National Cancer Institute. The datasets used in this analysis were accessed with appropriate approval through the dbGaP online resource (http://www.cgems.cancer.gov/data_acess.html) through dbGaP accession number 000207v.1p1.c1 (National Cancer Institute (2009) Cancer Genetic Markers of Susceptibility (CGEMS) data website http://cgems.cancer.gov/data_access.html; Yeager et al., 2007). Control samples were also genotyped as part of the GWAS of Lung Cancer and Smoking [Landi et al., 2009]. Funding for this work was provided through the National Institutes of Health, Genes, Environment and Health Initiative [NIH GEI] (Z01 CP 010200). The human subjects participating in the GWAS are derived from the Prostate, Lung, Colon and Ovarian Screening Trial and the study is supported by intramural resources of the National Cancer Institute. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01 HG 004438). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000093.; PMH: National Institutes of Health (R01 CA076366 to P.A.N.).; VITAL: National Institutes of Health (K05 CA154337).; WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 68 TC 10 Z9 11 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2013 VL 37 IS 5 BP 452 EP 464 DI 10.1002/gepi.21735 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 164CQ UT WOS:000320386800004 PM 23720162 ER PT J AU Skog, J Carter, B Balaj, L Hochberg, F Sivaraman, S Kim, R Breakefield, X AF Skog, J. Carter, B. Balaj, L. Hochberg, F. Sivaraman, S. Kim, R. Breakefield, X. TI GLIOMA MICROVESICLES (EXOSOMES) AS BIOIVIARKERS SO GLIA LA English DT Meeting Abstract CT 11th European Meeting on Glial Cell Function in Health and Disease CY JUL 03-06, 2013 CL Berlin, GERMANY C1 [Skog, J.] Exosome Diagnost Inc, New York, NY USA. [Carter, B.; Hochberg, F.; Kim, R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Balaj, L.; Hochberg, F.; Sivaraman, S.; Breakefield, X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-1491 J9 GLIA JI Glia PD JUL PY 2013 VL 61 SU 1 BP S40 EP S41 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 164KQ UT WOS:000320408400122 ER PT J AU Rosowski, JJ Puria, S AF Rosowski, John J. Puria, Sunil TI In Memory of Dr. Saumil Nalin Merchant (1960-2012) SO HEARING RESEARCH LA English DT Biographical-Item C1 [Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Puria, Sunil] Stanford Univ, Dept Mech Engn & Otolaryngol HNS, Stanford, CA 94305 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2013 VL 301 SI SI BP 1 EP 1 DI 10.1016/j.heares.2013.04.002 PG 1 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 165IW UT WOS:000320478100001 ER PT J AU Rosowski, JJ Dobrev, I Khaleghi, M Lu, WN Cheng, JT Harrington, E Furlong, C AF Rosowski, John J. Dobrev, Ivo Khaleghi, Morteza Lu, Weina Cheng, Jeffrey Tao Harrington, Ellery Furlong, Cosme TI Measurements of three-dimensional shape and sound-induced motion of the chinchilla tympanic membrane SO HEARING RESEARCH LA English DT Article ID WAVE MODEL; EARDRUM; HOLOGRAPHY; SURFACE AB Opto-electronic computer holographic measurements were made of the tympanic membrane (TM) in cadaveric chinchillas. Measurements with two laser wavelengths were used to compute the 3D-shape of the TM. Single laser wavelength measurements locked to eight distinct phases of a tonal stimulus were used to determine the magnitude and the relative phase of the surface displacements. These measurements were made at over 250,000 points on the TM surface. The measured motions contained spatial phase variations consistent with relatively low-order (large spatial frequency) modal motions and smaller magnitude higher-order (smaller spatial frequency) motions that appear to travel, but may also be explained by losses within the membrane. The measurement of shape and thin shell theory allowed us to separate the measured motions into those components orthogonal to the plane of the tympanic ring, and those components within the plane of the tympanic ring based on the 3D-shape. The predicted in-plane motion components are generally smaller than the out-of-plane perpendicular component of motion. Since the derivation of in-plane and out-of plane depended primarily on the membrane shape, the relative sizes of the predicted motion components did not vary with frequency. Summary: A new method for simultaneously measuring the shape and sound-induced motion of the tympanic membrane is utilized to estimate the 3D motion on the membrane surface. This article is part of a Special Issue entitled "MEMRO 2012". (C) 2012 Elsevier B.V. All rights reserved. C1 [Rosowski, John J.; Cheng, Jeffrey Tao; Furlong, Cosme] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Rosowski, John J.; Cheng, Jeffrey Tao; Furlong, Cosme] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Dobrev, Ivo; Khaleghi, Morteza; Lu, Weina; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. [Dobrev, Ivo; Khaleghi, Morteza; Lu, Weina; Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu OI Khaleghi Meybodi, Morteza/0000-0003-0123-7010 FU NIDCD; Mittal Foundation FX We thank Mike Ravicz, Jef Aernouts, and Saumil Merchant for significant contributions to this work. This work has been funded by NIDCD grants to JJR, and the Mittal Foundation. NR 37 TC 18 Z9 18 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2013 VL 301 SI SI BP 44 EP 52 DI 10.1016/j.heares.2012.11.022 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 165IW UT WOS:000320478100007 PM 23247058 ER PT J AU Chhan, D Roosli, C McKinnon, ML Rosowski, JJ AF Chhan, David Roeoesli, Christof McKinnon, Melissa L. Rosowski, John J. TI Evidence of inner ear contribution in bone conduction in chinchilla SO HEARING RESEARCH LA English DT Article ID MIDDLE-EAR; ADMITTANCE; PRESSURE AB We investigated the contribution of the middle ear to the physiological response to bone conduction stimuli in chinchilla. We measured intracochlear sound pressure in response to air conduction (AC) and bone conduction (BC) stimuli before and after interruption of the ossicular chain at the incudostapedial joint. Interruption of the chain effectively decouples the external and middle ear from the inner ear and significantly reduces the contributions of the outer ear and middle ear to the bone conduction response. With AC stimulation, both the scala vestibuli Psv and scala tympani Pst sound pressures drop by 30-40 dB after the interruption. In BC stimulation, Psv decreases after interruption by about 10-20 dB, but Pst is little affected. This difference in the sensitivity of the BC induced Psv and Pst to ossicular interruption is not consistent with a BC response to ossicular motion, but instead suggests a significant contribution of an inner-ear drive (e.g. cochlear fluid inertia or compressibility) to the BC response. This article is part of a Special Issue entitled "MEMRO 2012". (C) 2012 Elsevier B.V. All rights reserved. C1 [Chhan, David; Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Chhan, David; Roeoesli, Christof; McKinnon, Melissa L.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [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. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu FU NIDCD NIH HHS [T32 DC000038, R01 DC000194] NR 14 TC 9 Z9 9 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2013 VL 301 SI SI BP 66 EP 71 DI 10.1016/j.heares.2012.11.014 PG 6 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 165IW UT WOS:000320478100010 PM 23211609 ER PT J AU Stieger, C Rosowski, JJ Nakajima, HH AF Stieger, Christof Rosowski, John J. Nakajima, Hideko Heidi TI Comparison of forward (ear-canal) and reverse (round-window) sound stimulation of the cochlea SO HEARING RESEARCH LA English DT Article ID FLOATING MASS TRANSDUCER; MIXED HEARING LOSSES; HUMAN TEMPORAL BONES; HUMAN MIDDLE-EAR; VIBRANT SOUNDBRIDGE; PRESSURE MEASUREMENTS; INPUT IMPEDANCE; IMPLANTATION; VIBROPLASTY; PERFORMANCE AB The cochlea is normally driven with "forward" stimulation, in which sound is introduced to the ear canal. Alternatively, the cochlea can be stimulated at the round window (RW) using an actuator. During RW "reverse" stimulation, the acoustic flow starting at the RW does not necessarily take the same path as during forward stimulation. To understand the differences between forward and reverse stimulation, we measured ear-canal pressure, stapes velocity, RW velocity, and intracochlear pressures in scala vestibuli (SV) and scala tympani (ST) of fresh human temporal bones. During forward stimulation, the cochlear drive (differential pressure across the partition) results from the large difference in magnitude between the pressures of SV and ST, which occurs due to the high compliance of the RW. During reverse stimulation, the relatively high impedance of the middle ear causes the pressures of SV and ST to have similar magnitudes, and the differential pressure results primarily from the difference in phase of the pressures. Furthermore, the sound path differs between forward and reverse stimulation, such that motion through a third window is more significant during reverse stimulation. Additionally, we determined that although stapes velocity is a good estimate of cochlear drive during forward stimulation, it is not a good measure during reverse stimulation. This article is part of a Special Issue entitled "MEMRO 2012". (C) 2012 Elsevier B.V. All rights reserved. C1 [Stieger, Christof; Rosowski, John J.; Nakajima, Hideko Heidi] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Eaton Peabody Lab, Boston, MA 02114 USA. [Stieger, Christof] Univ Bern, ARTORG Ctr, Univ Dept ENT Head & Neck Surg, Inselspital, CH-3010 Bern, Switzerland. RP Nakajima, HH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu FU NIH [R03DC011158, R01DC004798] FX We dedicate this paper to Saumil N. Merchant, who was involved throughout this project contributing his insight and support. We thank Julie Merchant, Diane Jones, Mike Ravicz, Melissa McKinnon, Ishmael Stefanov-Wagner, David Chhan, Marlien Niesten, and the staff of the Otolaryngology Department and Eaton Peabody Laboratory at Massachusetts Eye and Ear Infirmary for their generous contributions. This work was carried out in part through the use of MIT's Microsystems Technology Laboratories for the fabrication of the micro fiberoptic pressure sensors. Support was provided by NIH grants R03DC011158 (HHN) and R01DC004798 (SNM). NR 32 TC 24 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2013 VL 301 SI SI BP 105 EP 114 DI 10.1016/j.heares.2012.11.005 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 165IW UT WOS:000320478100015 PM 23159918 ER PT J AU Backman, ES Triant, VA Ehrenfeld, JM Lu, Z Arpino, P Losina, E Gandhi, RT AF Backman, E. S. Triant, V. A. Ehrenfeld, J. M. Lu, Z. Arpino, P. Losina, E. Gandhi, R. T. TI Safety of midazolam for sedation of HIV-positive patients undergoing colonoscopy SO HIV MEDICINE LA English DT Article DE antiretrovirals; colonoscopy; HIV; midazolam; sedation ID INTRAVENOUS MIDAZOLAM; CONSCIOUS SEDATION; PHARMACOKINETICS; BRONCHOSCOPY; ANESTHESIA; ENDOSCOPY AB Objectives Because of concerns regarding interactions between midazolam and antiretroviral therapy (ART), alternative sedatives are sometimes used during procedural sedation. Our objective was to compare outcomes in patients on ART who received intravenous (iv) midazolam vs. iv diazepam, a second-line agent, during colonoscopy. Methods We conducted a retrospective analysis of adult HIV-positive patients who underwent colonoscopy over a 3.5-year period. Primary outcomes were sedation duration, nadir systolic blood pressure (SBP), nadir oxygen saturation, abnormal cardiac rhythm, and change in level of consciousness using a standardized scale. We calculated rates of adverse events according to benzodiazepine use and identified risk factors for complications using univariate and multivariate analyses. Results We identified 136 patients for this analysis: 70 received midazolam-based sedation and 66 received a diazepam-based regimen. There were no significant differences between the two groups with respect to sedation duration (mean 48.0 vs. 45.7 minutes for the midazolam and diazepam groups, respectively; P=0.68), nadir SBP (mean 97.0 vs. 101.6 mmHg; P=0.06), nadir oxygen saturation (mean 94.6 vs. 94.8%; P=0.72) or rate of abnormal cardiac rhythm (11.4 vs. 19.7%; P=0.18). More patients in the midazolam group experienced a depressed level of consciousness (91% vs. 74% in the diazepam group; P=0.0075), but no patient required reversal of sedation or became unresponsive. Conclusions We did not find evidence that patients who received midazolam for procedural sedation had clinical outcomes statistically different from those who received diazepam. These findings should be confirmed in prospective studies or in a randomized controlled trial. C1 [Backman, E. S.; Arpino, P.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Triant, V. A.; Gandhi, R. T.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Ehrenfeld, J. M.] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Lu, Z.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Losina, E.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. RP Backman, ES (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St,GRB 005, Boston, MA 02114 USA. EM ebackman@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140 FU National Institutes of Health (NIH) [R01 AI066992-04A1, G08LM008830-01, U01 AI 694722, 2P30 AI060354-06] FX RTG is supported by grants from the National Institutes of Health (NIH) (R01 AI066992-04A1 and NIH G08LM008830-01) and by grants to the AIDS Clinical Trials Group (NIH U01 AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06). NR 17 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 J9 HIV MED JI HIV Med. PD JUL PY 2013 VL 14 IS 6 BP 379 EP 384 DI 10.1111/hiv.12014 PG 6 WC Infectious Diseases SC Infectious Diseases GA 159IJ UT WOS:000320038800007 PM 23332038 ER PT J AU Vannini, P Hedden, T Sullivan, C Sperling, RA AF Vannini, Patrizia Hedden, Trey Sullivan, Caroline Sperling, Reisa A. TI Differential functional response in the posteromedial cortices and hippocampus to stimulus repetition during successful memory encoding SO HUMAN BRAIN MAPPING LA English DT Article DE episodic memory; functional MRI; hippocampus; posteromedial cortex; repetition ID MILD COGNITIVE IMPAIRMENT; INFERIOR TEMPORAL CORTEX; LONG-TERM-MEMORY; RECOGNITION MEMORY; DEFAULT NETWORK; FACE PERCEPTION; AUTOBIOGRAPHICAL MEMORY; PARIETAL DEACTIVATION; ALZHEIMERS-DISEASE; NEURAL MECHANISMS AB The reduction of neural activity in response to repeated stimuli, repetition suppression, is one of the most robust experience-related cortical dynamics known to cognitive neuroscience. Functional magnetic resonance imaging (fMRI) studies during episodic memory encoding have demonstrated repetition suppression in the hippocampus and this reduction has been linked to successful memory formation. An emerging body of functional imaging evidence suggests that the posteromedial cortex, in addition to the medial temporal lobes, may have a pivotal role in successful episodic memory. This area typically deactivates during initial memory encoding, but its functional changes in response to repetitive encoding remain poorly specified. Here, we investigate the repetition-related changes in the posteromedial cortex as well as the hippocampus while the participants underwent an fMRI experiment involving repetitive encoding of face-name pairs. During the first encoding trial of face-name pairs, significant activation in the hippocampus was observed. The second and third encoding trials demonstrated a repetition suppression effect in the hippocampus, indicated by a stepwise decrease of activation. In contrast, the posteromedial cortex demonstrated significant deactivation during the initial encoding trial of face-name pairs. The second and third encoding trials demonstrated a stepwise decrease of deactivation, repetition enhancement, with activity at or above baseline levels in the final encoding trial. These findings demonstrate that hippocampus repetition suppression as well as posteromedial repetition enhancement is related to successful encoding processes and are discussed in relation to the default mode hypothesis as well as potential implications for understanding late-life amnestic disorders. Hum Brain Mapp, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Vannini, Patrizia; Sperling, Reisa A.] Harvard Univ, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Vannini, Patrizia; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Vannini, Patrizia] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Neurobiol Care Sci & Soc,Div Clin Geriatr, Stockholm, Sweden. [Hedden, Trey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Sullivan, Caroline; Sperling, Reisa A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. RP Vannini, P (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Boston, MA 02129 USA. EM patrizia@nmr.mgh.harvard.edu FU Swedish Brain foundation; Swedish Society for Medicine; Marie Curie Fellowship from European Union [FP7-PEOPLE-2007-4-1-IOF]; National Institutes of Health [R01 AG027435-S1, P01AG036694, P50AG00513421]; Alzheimer's Association [IIRG-06-27374] FX The authors are indebted to the volunteers who participated in this study. They thank Janice Fairhurst, Seung-Schik Yoo, George Chiuo, and Istvan Akos Morocz for their help with scan acquisition at the Center for Advanced Imaging at Brigham and Women's Hospital. This work was supported by the Swedish Brain foundation (P. V.), The Swedish Society for Medicine (P. V.), and Marie Curie Fellowship: FP7-PEOPLE-2007-4-1-IOF from the European Union (P. V.). National Institutes of Health: R01 AG027435-S1 (R. S.), P01AG036694 (R. S.), P50AG00513421 (R. S.), and the Alzheimer's Association: IIRG-06-27374 (R. S.). NR 74 TC 18 Z9 18 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2013 VL 34 IS 7 BP 1568 EP 1578 DI 10.1002/hbm.22011 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 164KH UT WOS:000320407500006 PM 22344847 ER PT J AU Suzuki, E Williams, S Sato, S Gilkeson, G Watson, DK Zhang, XK AF Suzuki, Eiji Williams, Sarah Sato, Shuzo Gilkeson, Gary Watson, Dennis K. Zhang, Xian K. TI The transcription factor Fli-1 regulates monocyte, macrophage and dendritic cell development in mice SO IMMUNOLOGY LA English DT Article DE dendritic cells; Fli-1 transcription factor; Fms-related tyrosine kinase 3 ligand; macrophages; monocytes ID GENE-TARGETED MICE; MARGINAL ZONE; FLT3 LIGAND; ETS FAMILY; IN-VIVO; EXPRESSION; MEGAKARYOPOIESIS; DIFFERENTIATION; PROLIFERATION; HOMEOSTASIS AB Fli-1 belongs to the Ets transcription factor family and is expressed in haematopoietic cells, including most of the cells that are active in immunity. The mononuclear phagocytes, i.e. monocytes, macrophages and dendritic cells, originate in haematopoietic stem cells and play an important role in immunity. To assess the role of Fli-1 in mononuclear phagocyte development in vivo, we generated mice that express a truncated Fli-1 protein, lacking the C-terminal transcriptional activation domain (Fli-1CTA). Fli-1CTA/CTA mice had significantly increased populations of haematopoietic stem cells and common dendritic cell precursors in bone marrow compared with wild-type littermates. Significantly increased classical dendritic cells, plasmacytoid dendritic cells, and macrophage populations were found in spleens from Fli-1CTA/CTA mice compared with wild-type littermates. Fli-1CTA/CTA mice also had increased pre-classical dendritic cell and monocyte populations in peripheral blood mononuclear cells. Furthermore, bone marrow reconstitution studies demonstrated that expression of Fli-1 in both haematopoietic cells and stromal cells affected mononuclear phagocyte development in mice. Expression of Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic growth factor, in multipotent progenitors was statistically significantly increased from Fli-1CTA/CTA mice compared with wild-type littermates. Fli-1 protein binds directly to the promoter region of the Flt3L gene. Hence, Fli-1 plays an important role in the mononuclear phagocyte development, and the C-terminal transcriptional activation domain of Fli-1 negatively modulates mononuclear phagocyte development. C1 [Suzuki, Eiji; Sato, Shuzo; Gilkeson, Gary; Zhang, Xian K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Williams, Sarah; Gilkeson, Gary; Zhang, Xian K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St MSC637,Suite 912, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU National Institutes of Health [AR056670]; Medical Research Service, Department of Veterans Affairs FX This study was supported in part by National Institutes of Health grants (AR056670 to X.K.Z.) and the Medical Research Service, Department of Veterans Affairs (to G. G. and X.K.Z.). We thank Dr Mara Lennard-Richard at the Medical University of South Carolina for critical reading of the manuscript. NR 39 TC 6 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 2013 VL 139 IS 3 BP 318 EP 327 DI 10.1111/imm.12070 PG 10 WC Immunology SC Immunology GA 164EU UT WOS:000320392500007 PM 23320737 ER PT J AU Villar, J Kacmarek, RM AF Villar, Jesus Kacmarek, Robert M. TI What is new in refractory hypoxemia? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; EXTRACORPOREAL MEMBRANE-OXYGENATION; ACUTE LUNG INJURY; HIGH-FREQUENCY OSCILLATION; END-EXPIRATORY PRESSURE; RECRUITMENT; FAILURE; ECMO C1 [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria 35010, Spain. [Villar, Jesus] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria 35010, Spain. RP Villar, J (reprint author), Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Barranco Ballena S-N,4th Floor,South Wing, Las Palmas Gran Canaria 35010, Spain. EM jesus.villar54@gmail.com NR 26 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUL PY 2013 VL 39 IS 7 BP 1207 EP 1210 DI 10.1007/s00134-013-2905-0 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 163KF UT WOS:000320334100004 PM 23575611 ER PT J AU Kereakoglow, S Gelman, R Partridge, AH AF Kereakoglow, Sandra Gelman, Rebecca Partridge, Ann H. TI Evaluating the effect of esthetically enhanced materials compared to standard materials on clinician response rates to a mailed survey SO INTERNATIONAL JOURNAL OF SOCIAL RESEARCH METHODOLOGY LA English DT Article DE survey response rate; enhanced survey materials; clinician response to mailed survey; survey design; survey research ID PHYSICIAN RESPONSE; RANDOMIZED-TRIAL; QUESTIONNAIRES; INCENTIVES; 5-DOLLAR AB Evidence suggests that physicians have lower response rates than nonphysicians to mailed surveys. It is important to identify methods that can increase physician and nurse participation in health-related survey research. In an effort to improve response rates among clinicians, we developed esthetically enhanced survey materials (booklets printed on glossy paper with color and graphic designs) as part of a large mailed-survey study of oncology doctors and nurses who were listed as members of a North American cooperative oncology group. We randomized these clinicians to receive either an enhanced (90%) or standard (10%) paper survey (standard white paper with no color nor graphic designs, stapled together) about offering results of clinical trials to trial participants. Overall, 34% (793/2333) of the surveys were returned. There was no significant difference between the two groups; 33.7% (707/2300) responded to the enhanced materials and 36.9% (86/233) responded to the standard materials (p=.34). These results suggest that esthetically enhanced materials do not increase clinician response rates to mailed surveys, although further research is warranted in this area. C1 [Kereakoglow, Sandra; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1364-5579 J9 INT J SOC RES METHOD JI Int. J. Soc. Res. Methodol. PD JUL 1 PY 2013 VL 16 IS 4 BP 301 EP 306 DI 10.1080/13645579.2012.682430 PG 6 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 163SG UT WOS:000320356600003 ER PT J AU Neumeyer, AM Gates, A Ferrone, C Lee, H Misra, M AF Neumeyer, Ann M. Gates, Amy Ferrone, Christine Lee, Hang Misra, Madhusmita TI Bone Density in Peripubertal Boys with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Autism spectrum disorder; Bone density; Puberty; Bone turnover; Bone metabolism ID VITAMIN-D DEFICIENCY; MINERAL DENSITY; ANOREXIA-NERVOSA; ADOLESCENT GIRLS; HEALTHY-CHILDREN; GROWTH-HORMONE; MASS; TURNOVER; DISEASE; ACQUISITION AB We determined whether bone mineral density (BMD) is lower in boys with autism spectrum disorders (ASD) than controls, and also assessed variables that may affect BMD in ASD. BMD was measured using dual energy X-ray absorptiometry (DXA) in 18 boys with ASD and 19 controls 8-14 years old. Boys with ASD had lower BMD Z-scores at the spine, hip and femoral neck, and differences at the hip and femoral neck persisted after controlling for maturity and BMI. Vitamin D intake from food and in serum were lower in ASD subjects, as was exercise activity. We conclude that BMD is lower in peripubertal boys with ASD and may be associated with impaired vitamin D status and lower exercise activity. C1 [Neumeyer, Ann M.; Gates, Amy; Ferrone, Christine] Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA. [Neumeyer, Ann M.] Harvard Univ, Sch Med, Lexington, MA 02421 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Lee, Hang; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Neumeyer, AM (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, 1 Maguire Rd, Lexington, MA 02421 USA. EM aneumeyer@partners.org FU NCRR NIH HHS [1 UL1 RR025758-01, UL1 RR025758]; NICHD NIH HHS [K24 HD071843]; PHS HHS [UA3 MC 11054] NR 36 TC 16 Z9 18 U1 1 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUL PY 2013 VL 43 IS 7 BP 1623 EP 1629 DI 10.1007/s10803-012-1709-3 PG 7 WC Psychology, Developmental SC Psychology GA 165TO UT WOS:000320507200012 PM 23124396 ER PT J AU Pati, S Sollman, M Fife, TD Ng, YT AF Pati, Sandipan Sollman, Myriam Fife, Terry D. Ng, Yu-Tze TI Diagnosis and Management of Epilepsy Associated With Hypothalamic Hamartoma: An Evidence-Based Systematic Review SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE hypothalamic hamartoma; epilepsy; systematic review ID GAMMA-KNIFE SURGERY; QUALITY STANDARDS SUBCOMMITTEE; GELASTIC SEIZURES; INTRACTABLE EPILEPSY; PSYCHIATRIC COMORBIDITY; TRANSCALLOSAL RESECTION; REFRACTORY EPILEPSY; PRECOCIOUS PUBERTY; PRACTICE PARAMETER; AMERICAN-ACADEMY AB The main objective was to review the evidence for management of epilepsy associated with hypothalamic hamartomas. We performed a systemic review of the literature through July 2012 that studied patients with hypothalamic hamartomas and related epilepsy. Articles meeting selection criteria were rated according to the American Academy of Neurology classification of evidence scheme. Recommendations were linked to the strength of the evidence and as follows: (a) precocious puberty is associated more with the pedunculated type and epilepsy typified by gelastic seizures with the sessile form of hypothalamic hamartomas (class III); (b) significant behavioral and cognitive deficits are associated with patients with hypothalamic hamartomas (class III); (c) video electroencephalography (EEG) findings are extremely variable particularly across the different ages and do not affect surgical outcome (class III); d) various surgical techniques (transcallosal and endoscopic resection) resulted in 49% to 54% seizure freedom, 15% with a pterional approach as well as about 40% with radiosurgery (class III). C1 [Pati, Sandipan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02411 USA. [Sollman, Myriam] Wake Forest Univ, Baptist Med Ctr, Dept Neurol Neuropsychol, Winston Salem, NC 27109 USA. [Fife, Terry D.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. [Ng, Yu-Tze] Univ Oklahoma, Coll Med, Dept Child Neurol, Oklahoma City, OK 73190 USA. RP Pati, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02411 USA. EM spati@partners.org NR 41 TC 9 Z9 10 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUL PY 2013 VL 28 IS 7 BP 909 EP 916 DI 10.1177/0883073813488673 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 166ZJ UT WOS:000320599500010 PM 23670254 ER PT J AU Bell, ME Cattaneo, LB Goodman, LA Dutton, MA AF Bell, Margret E. Cattaneo, Lauren Bennett Goodman, Lisa A. Dutton, Mary Ann TI Criminal Case Outcomes, Incarceration, and Subsequent Intimate Partner Violence SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Battered women; Criminal court; Abuse; Legal ID COORDINATED COMMUNITY INTERVENTION; DOMESTIC VIOLENCE; TRAUMA RESEARCH; RECIDIVISM; PROSECUTION; ASSAULT; ARREST; CRIME; DISPOSITIONS; REGRESSION AB Given the centrality of court interventions to the U.S. response to intimate partner violence (IPV), it is crucial to evaluate their impact on reabuse. To do so, this study examined whether female IPV victims' experiences of abuse in the year following a criminal court case against their partner varied by case outcome or by whether the batterer had or had not been incarcerated. Consistent with prior research, we found no main effect differences in reabuse trajectories by court case outcome or by incarceration. We also examined variables that might moderate the impact of case outcome and incarceration on reabuse and found that although batterer legal history did not affect the impact of case outcome, his age, Time 1 employment status, the couple's Time 1 living arrangement, and duration of abuse did interact with case outcome. No variables tested moderated the relationship between incarceration and reabuse over time. Findings suggest that in certain cases there may be benefits to case outcomes that leave potential consequences hanging over the offender's head. These results also add to the growing body of evidence questioning the efficacy of one-size-fits-all approaches to IPV cases. C1 [Bell, Margret E.] Vet Affairs VA Boston Healthcare Syst, Boston, MA USA. [Bell, Margret E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Cattaneo, Lauren Bennett] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Goodman, Lisa A.] Boston Coll, Dept Counseling Dev & Educ Psychol, Lynch Sch Educ, Chestnut Hill, MA 02167 USA. [Dutton, Mary Ann] Georgetown Univ, Dept Psychiat, Washington, DC USA. [Bell, Margret E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. RP Bell, ME (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM mebell@aya.yale.edu NR 42 TC 3 Z9 3 U1 1 U2 23 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD JUL PY 2013 VL 28 IS 5 BP 489 EP 502 DI 10.1007/s10896-013-9515-z PG 14 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 163CW UT WOS:000320314300007 ER PT J AU Dismuke, CE Egede, LE AF Dismuke, Clara E. Egede, Leonard E. TI Medicare Part D Prescription Drug Program: Benefits, Unintended Consequences and Impact on Health Disparities SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID COVERAGE GAP; BENEFICIARIES; ADHERENCE C1 [Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 9 TC 2 Z9 2 U1 0 U2 6 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 JUL PY 2013 VL 28 IS 7 BP 860 EP 861 DI 10.1007/s11606-013-2423-3 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 165TU UT WOS:000320508100002 PM 23539284 ER PT J AU Sacks, NC Burgess, JF Cabral, HJ Pizer, SD McDonnell, ME AF Sacks, Naomi C. Burgess, James F., Jr. Cabral, Howard J. Pizer, Steven D. McDonnell, Marie E. TI Cost Sharing and Decreased Branded Oral Anti-Diabetic Medication Adherence Among Elderly Part D Medicare Beneficiaries SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Medicare; medication adherence; diabetes; Part D; coverage gap ID CHRONIC DISEASE SCORE; HEALTH-CARE COSTS; TYPE-2 DIABETES-MELLITUS; AUTOMATED PHARMACY DATA; PRESCRIPTION DRUGS; COVERAGE GAP; DUTCH SITUATION; RISK ADJUSTMENT; BENEFITS; IMPACT AB Although the Medicare Part D coverage gap phase-out should reduce cost-related nonadherence (CRN) among seniors with diabetes, preferential generic prescribing may have already decreased CRN, while smaller numbers of patients using more costly branded oral anti-diabetic (OAD) medications remain vulnerable to CRN. To estimate the effects of cost sharing in the Part D standard (non-LIS) benefit on adherence to different OAD classes, comparing two classes dominated by inexpensive generic medications and two by more costly branded medications. Retrospective cohort study using dispensed prescription data for elderly non-LIS (N = 81,047) and LIS (low-income subsidy) (N = 150,359) beneficiaries using same class OAD(s) in 2008 and 2009. Logistic regression modeled non-LIS likelihood; LIS and non-LIS patients matched using propensity outcome (N = 38,054). Logistic regression, controlling for demographic and health status characteristics, modeled effects of non-LIS coverage on 2009 OAD class adherence. Main outcome measures were within-class OAD coverage year adherence, with patients considered adherent when days supplied to calendar days ratio at least 0.8. Non-LIS patients had 0.52 and 0.57 times the odds of branded-only DPP-4 Inhibitor (N = 1,812; 95 % CI: 0.43, 0.63; P < 0.001) and Thiazolidinedione (TZD) (N = 6,290; 95 % CI: 0.52, 0.63; P < 0.001) adherence. Most patients (N = 32,510; 82 %) used OADs in primarily generic classes, where we found no significant (Biguanides; N = 21,377) or small differences (Sulfonylureas/Glinides [N = 19,240; OR: 0.91; 95 % CI: 0.86, 0.97; P = 0.002]) in adherence odds. Crude adherence rates were sub-optimal when CRN was not a factor (Non-LIS/LIS: Biguanides: 65 %/65 %; Sulfonylureas/Glinides: 66 %/68 %; LIS: DPP-4 Inhibitors: 66 %; TZDs: 67 %). Gap elimination would not affect generic, but should reduce branded OAD CRN. Branded copayments may continue to lead to CRN. Policy initiatives and benefit changes targeting both cost deterrents for patients with more complex disease and non-cost generic OAD underuse are recommended. C1 [Burgess, James F., Jr.] VA Boston, Ctr Org Leadership & Management Res, Boston, MA USA. [Sacks, Naomi C.; Burgess, James F., Jr.; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Sacks, Naomi C.] IMS Hlth Payer Solut, Waltham, MA USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [McDonnell, Marie E.] Boston Med Ctr, Endocrinol Sect, Dept Med, Boston, MA USA. [McDonnell, Marie E.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Pizer, Steven D.] VA Boston Healthcare Syst, Hlth Care Financing & Econ, Boston, MA USA. RP Sacks, NC (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 715 Albany St, Boston, MA 02118 USA. EM nsacks@bu.edu OI Burgess, James/0000-0002-6646-7071; McDonnell, Marie/0000-0003-3892-2660; Cabral, Howard/0000-0002-1185-8331 NR 65 TC 8 Z9 8 U1 3 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 JUL PY 2013 VL 28 IS 7 BP 876 EP 885 DI 10.1007/s11606-013-2342-3 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 165TU UT WOS:000320508100011 PM 23404199 ER PT J AU Washington, DL Davis, TD Der-Martirosian, C Yano, EM AF Washington, Donna L. Davis, Teri D. Der-Martirosian, Claudia Yano, Elizabeth M. TI PTSD Risk and Mental Health Care Engagement in a Multi-War Era Community Sample of Women Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE post-traumatic stress disorder; women; veterans; mental health services; utilization; Veterans hospitals ID POSTTRAUMATIC-STRESS-DISORDER; SHORT SCREENING SCALE; FEMALE VETERANS; SERVICE USE; VA; IRAQ; COMORBIDITY; AFGHANISTAN; PREVALENCE; POPULATION AB Post-traumatic stress disorder (PTSD) is common in women veterans (WVs), and associated with significant co-morbidity. Effective treatment is available; however, PTSD is often unrecognized. Identify PTSD prevalence and mental healthcare (MHC) use in a representative national WV sample. Cross-sectional, population-based 2008-2009 national survey of 3,611 WVs, weighted to the population. We screened for PTSD using a validated instrument, and also assessed demographic characteristics, health characteristics, and MHC use in the prior 12 months. Among those screening positive, we conducted multivariate logistic regression to identify independent predictors of MHC use. Overall, 13.0 % (95 % confidence interval [CI] 9.8-16.2) of WVs screened PTSD-positive. Veterans Health Administration (VA) healthcare was used by 31.1 % of PTSD-positives and 11.4 % of PTSD-negatives (p < 0.001). Among those screening positive, 48.7 % (95 % CI 35.9-61.6) used MHC services (66.3 % of VA-users, 40.8 % of VA-nonusers; p < 0.001). Having a diagnosis of depression (OR = 8.6; 95 % CI 1.5-48.9) and VA healthcare use (OR = 2.7; 95 % CI 1.1-7.0) predicted MHC use, whereas lacking a regular provider for health care (OR = 0.2; 95 % CI 0.1-0.4) and household income below the federal poverty level (OR = 0.2; 95 % CI 0.1-0.5) predicted nonuse. More than one in eight WVs screened positive for PTSD. Though a majority of VA-users received MHC, low income predicted nonuse. Only a minority of VA-nonusers received MHC. The majority of WVs use non-VA healthcare providers, who may be unaware of their veteran status and PTSD risk. VA outreach to educate VA-nonusers and their healthcare providers about WVs' PTSD risk and available evidence-based VA treatment options is one approach to extend the reach of VA MHC. Research to characterize barriers to VA MHC use for VA-nonusers and low income VA-users is warranted to better understand low service utilization, and to inform program development to engage more WVs in needed MHC. C1 [Washington, Donna L.; Davis, Teri D.; Der-Martirosian, Claudia; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Serv Res & Dev HSR&D, Sepulveda, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Yano, Elizabeth M.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM Donna.washington@va.gov FU Department of Veterans Affairs, Women's Health Services in the Office of Patient Care Services; Health Services Research and Development (HSRD) Service [IAE-06-083, SDR-08-270]; VA HSR&D Senior Research Career Scientist award [RCS-05-195] FX This study was funded by the Department of Veterans Affairs, Women's Health Services in the Office of Patient Care Services and the Health Services Research and Development (HSR&D) Service (#IAE-06-083 and #SDR-08-270). Dr. Yano is supported by a VA HSR&D Senior Research Career Scientist award (#RCS-05-195). The views expressed within are solely those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs. NR 35 TC 18 Z9 18 U1 0 U2 5 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 JUL PY 2013 VL 28 IS 7 BP 894 EP 900 DI 10.1007/s11606-012-2303-2 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 165TU UT WOS:000320508100013 PM 23435765 ER PT J AU Tilstra, SA Kraemer, KL Rubio, DM McNeil, MA AF Tilstra, Sarah A. Kraemer, Kevin L. Rubio, Doris M. McNeil, Melissa A. TI Evaluation of VA Women's Health Fellowships: Developing Leaders in Academic Women's Health SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE VA women's health; fellowship; academic productivity; female leadership; women in academic medicine ID GENERAL INTERNAL-MEDICINE; EDITORIAL-BOARDS; CAREER; PHYSICIANS; PROGRAM; FACULTY; PRODUCTIVITY; VETERANS; IMPACT AB The Department of Veterans Affairs (VA) instituted the VA Women's Health Fellowship (VAWHF) Program in 1994, to accommodate the health needs of increasing numbers of female veterans and to develop academic leaders in women's health. Despite the longevity of the program, it has never been formally evaluated. To describe the training environments of VAWHFs and career outcomes of female graduates. Cross-sectional web-based surveys of current program directors (2010-2011) and VAWHF graduates (1995-2011). Responses were received from six of seven program directors (86 %) and 42 of 74 graduates (57 %). The mean age of graduates was 41.2 years, and mean time since graduation was 8.5 years. Of the graduates, 97 % were female, 74 % trained in internal medicine, and 64 % obtained an advanced degree. Those with an advanced degree were more likely than those without an advanced degree to pursue an academic career (82 % vs. 60 %; P < 0.01). Of the female graduates, 76 % practice clinical women's health and spend up to 66 % of their time devoted to women's health issues. Thirty percent have held a VA faculty position. Seventy-nine percent remain in academics, with 39 % in the tenure stream. Overall, 94 % had given national presentations, 88 % had received grant funding, 79 % had published in peer-reviewed journals, 64 % had developed or evaluated curricula, 51 % had received awards for teaching or research, and 49 % had held major leadership positions. At 11 or more years after graduation, 33 % of the female graduates in academics had been promoted to the rank of associate professor and 33 % to the rank of full professor. The VAWHF Program has been successful in training academic leaders in women's health. Finding ways to retain graduates in the VA system would ensure continued clinical, educational, and research success for the VA women veteran's healthcare program. C1 [Tilstra, Sarah A.; McNeil, Melissa A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Tilstra, Sarah A.; Kraemer, Kevin L.; Rubio, Doris M.; McNeil, Melissa A.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. [Kraemer, Kevin L.; Rubio, Doris M.; McNeil, Melissa A.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. RP Tilstra, SA (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, Dept Med, 200 Lothrop St,MUH W933, Pittsburgh, PA 15213 USA. EM tilstrasa@upmc.edu FU NCATS NIH HHS [UL1 TR000005] NR 27 TC 5 Z9 5 U1 1 U2 9 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 JUL PY 2013 VL 28 IS 7 BP 901 EP 907 DI 10.1007/s11606-012-2306-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 165TU UT WOS:000320508100014 PM 23435766 ER PT J AU Bloomfield, GS Yi, SS Astor, BC Kramer, H Shea, S Shlipak, MG Post, WS AF Bloomfield, G. S. Yi, S. S. Astor, B. C. Kramer, H. Shea, S. Shlipak, M. G. Post, W. S. TI Blood pressure and chronic kidney disease progression in a multi-racial cohort: the Multi-Ethnic Study of Atherosclerosis SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE blood pressure; glomerular filtration rate; renal disease; cystatin C; creatinine; ethnicity ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; CHRONIC RENAL-DISEASE; FUNCTION DECLINE; HYPERTENSION; CREATININE; ADULTS; TRIAL; RISK; METAANALYSIS AB The relationship between blood pressure (BP) and kidney function among individuals with chronic kidney disease (CKD) remains controversial. This study evaluated the association between BP and estimated glomerular filtration rate (eGFR) decline among adults with nondiabetic stage 3 CKD. The Multi-Ethnic Study of Atherosclerosis participants with an eGFR 30-59 ml min(-1) per 1.73 m(2) at baseline without diabetes were included. Participants were followed over a 5-year period. Kidney function change was determined by annualizing the change in eGFR using cystatin C, creatinine and a combined equation. Risk factors for progression of CKD (defined as a decrease in annualized eGFR > 2.5 ml min(-1) per 1.73 m(2)) were identified using univariate analyses and sequential logistic regression models. There were 220 participants with stage 3 CKD at baseline using cystatin C, 483 participants using creatinine and 381 participants using the combined equation. The median (interquartile range) age of the sample was 74 (68-79) years. The incidence of progression of CKD was 16.8% using cystatin C and 8.9% using creatinine (P = 0.002). Systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg was significantly associated with progression using a cystatin C-based (odds ratio (OR), 2.49; 95% confidence interval (CI), 1.12-5.52) or the combined equation (OR, 2.07; 95% CI, 1.16-3.69), but not when using creatinine after adjustment for covariates. In conclusion, with the inclusion of cystatin C in the eGFR assessment hypertension was an important predictor of CKD progression in a multi-ethnic cohort with stage 3 CKD. C1 [Bloomfield, G. S.] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. [Bloomfield, G. S.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Yi, S. S.; Astor, B. C.; Post, W. S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Astor, B. C.] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Astor, B. C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kramer, H.] Loyola Med Ctr, Dept Prevent Med, Maywood, IL USA. [Shea, S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Shea, S.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Shlipak, M. G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, M. G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Post, W. S.] Johns Hopkins Sch Med, Dept Med, Div Cardiol, Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. RP Post, WS (reprint author), Johns Hopkins Univ, Dept Med, Div Cardiol, Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM wpost@jhmi.edu OI Kramer, Holly/0000-0002-6374-837X; Bloomfield, Gerald/0000-0002-7176-1611; Yi, Stella/0000-0002-9943-2609 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169, K01 TW008407-02, R01 DK066488-01] FX We thank the other investigators, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute, K01 TW008407-02 (to GSB) and R01 DK066488-01 (to MGS). NR 32 TC 5 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JUL PY 2013 VL 27 IS 7 BP 421 EP 426 DI 10.1038/jhh.2013.1 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 162EP UT WOS:000320248400005 PM 23407373 ER PT J AU Dowlatshahi, M Huang, V Gehad, AE Jiang, Y Calarese, A Teague, JE Dorosario, AA Cheng, JW Nghiem, P Schanbacher, CF Thakuria, M Schmults, CD Wang, LC Clark, RA AF Dowlatshahi, Mitra Huang, Victor Gehad, Ahmed E. Jiang, Ying Calarese, Adam Teague, Jessica E. Dorosario, Andrew A. Cheng, Jingwei Nghiem, Paul Schanbacher, Carl F. Thakuria, Manisha Schmults, Chrysalyne D. Wang, Linda C. Clark, Rachael A. TI Tumor-Specific T Cells in Human Merkel Cell Carcinomas: A Possible Role for Tregs and T-Cell Exhaustion in Reducing T-Cell Responses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; DENDRITIC CELLS; HUMAN-SKIN; POLYOMAVIRUS; ANTIGEN; EXPRESSION; REGRESSION; CD8(+); IDENTIFICATION AB Merkel cell carcinomas (MCCs) are rare but highly malignant skin cancers associated with a recently described polyomavirus. MCC tumors were infiltrated by T cells, including effector, central memory, and regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T-cell activation, proliferation, enhanced cytokine production, and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting that tumor-specific T cells capable of controlling tumor growth were present in MCC. Both CD4(+) and CD8(+) FOXP3(+) regulatory T cells were frequent in MCC. Fifty percent of nonactivated T cells in MCC-expressed PD-1, a marker of T-cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T-cell activity, block regulatory T cell function, or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer. C1 [Dowlatshahi, Mitra; Huang, Victor; Gehad, Ahmed E.; Teague, Jessica E.; Thakuria, Manisha; Schmults, Chrysalyne D.; Clark, Rachael A.] Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. [Jiang, Ying] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Calarese, Adam] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Dorosario, Andrew A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cheng, Jingwei] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cheng, Jingwei] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Nghiem, Paul] Univ Washington, Sch Med, Dept Med, Fred Hutchinson Canc Res Ctr,Dermatol Div, Seattle, WA 98195 USA. [Schanbacher, Carl F.] Tufts Med Sch, Dept Dermatol, Boston, MA USA. [Wang, Linda C.] Mercy Med Ctr, Merkel Cell Carcinoma Program, Baltimore, MD USA. RP Clark, RA (reprint author), Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, EBRC Room 505A,221 Longwood Ave, Boston, MA 02115 USA. EM rclark1@partners.org RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X FU NIH/NIAMS [R01 AR056720, T32-AR07098-33]; NIH/NIMH [R03 MH095529]; NIH [R01AI097128]; Damon Runyon Cancer Research Foundation Clinical Investigator Award; Scleroderma Foundation New Investigator Award; American Skin Association Medical Student Grant; Skin Cancer Foundation Joseph A. Stirrup Research Award; Dermatology Foundation Dermatologist Investigator Research Fellowship; Women's Dermatologic Society Academic Research Grant Award FX We thank the patients for their donation of tissues that made these studies possible. Normal skin was kindly provided by Drs Bohdan Pomahac, Simon Talbot, and Elof Eriksson of Brigham and Women's Hospital, and by Dr Thomas Cochran of the Boston Center. Dr Jessica Scanlon. assisted with patient outcomes. Dr Thomas S. Kupper provided helpful advice and support. This research was supported by grants NIH/NIAMS R01 AR056720 (to RAC), NIH/NIMH R03 MH095529 (to RAC), NIH R01AI097128 (to RAC/TSK), a Damon Runyon Cancer Research Foundation Clinical Investigator Award (to RAC), a Scleroderma Foundation New Investigator Award (to RAC), an American Skin Association Medical Student Grant (to MD), a Skin Cancer Foundation Joseph A. Stirrup Research Award (to VH), Dermatology Foundation Dermatologist Investigator Research Fellowship (to VH), a Women's Dermatologic Society Academic Research Grant Award (to VH), and NIH/NIAMS T32-AR07098-33 (to TSK, supporting VH). NR 56 TC 27 Z9 29 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2013 VL 133 IS 7 BP 1879 EP 1889 DI 10.1038/jid.2013.75 PG 11 WC Dermatology SC Dermatology GA 164RY UT WOS:000320428400028 PM 23419694 ER PT J AU Brinkman, TM Liptak, CC Delaney, BL Chordas, CA Muriel, AC Manley, PE AF Brinkman, Tara M. Liptak, Cori C. Delaney, Brian L. Chordas, Christine A. Muriel, Anna C. Manley, Peter E. TI Suicide ideation in pediatric and adult survivors of childhood brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE CNS tumors; Suicide; Survivorship ID NATIONAL-COMORBIDITY-SURVEY; CANCER SURVIVOR; 5-YEAR SURVIVORS; LATE MORTALITY; RISK; ADOLESCENTS; PREVALENCE; SURGERY AB Survivors of pediatric brain tumors are at risk for long-term psychological morbidities. The current study investigated the prevalence and predictors of suicide ideation (SI) in a clinical sample of youth and adult survivors. Retrospective chart reviews were completed for 319 survivors of pediatric brain tumors who were assessed via clinical interview during routine neuro-oncology clinic visits between 2003 and 2007. Survivors were, on average, 18.0 years of age (SD = 4.9) and 10 years from diagnosis (SD = 5.0) at their most recent follow-up. The most common diagnosis was low-grade glioma (n = 162) followed by embryonal tumors (PNET/medulloblastoma; n = 64). Multivariable logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for SI. Nearly 12 % of survivors (11.7 %, n = 37) reported SI. Five survivors (1.5 %) had documented suicide attempts, though none were fatal. In a multivariable model, adjusting for sex and age, history of depression (OR = 20.6, 95 % CI = 4.2-101.1), psychoactive medication treatment (OR = 4.5, 95 % CI = 1.8-11.2), observation or surgery only treatment (OR = 3.7, 95 % CI = 1.5-9.1), and seizures (OR = 3.6, 95 % CI = 1.1-11.1) were significantly associated with SI in survivors. Survivors of pediatric brain tumors appear to be at risk for experiencing SI. Our results underscore the importance of a multidisciplinary approach to providing follow-up care for childhood brain tumor survivors, including routine psychological screenings. C1 [Brinkman, Tara M.; Liptak, Cori C.; Delaney, Brian L.; Muriel, Anna C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Chordas, Christine A.; Manley, Peter E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Brinkman, TM (reprint author), St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM tara.brinkman@stjude.org FU Stop and Shop Family Pediatric Neuro-Oncology Outcomes Clinic; Pediatric Brain Tumor Clinical and Research Fund at the Dana-Farber Cancer Institute FX This work was supported, in part, by the Stop and Shop Family Pediatric Neuro-Oncology Outcomes Clinic and the Pediatric Brain Tumor Clinical and Research Fund at the Dana-Farber Cancer Institute. NR 36 TC 13 Z9 13 U1 1 U2 10 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 JUL PY 2013 VL 113 IS 3 BP 425 EP 432 DI 10.1007/s11060-013-1130-6 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 165CU UT WOS:000320461300011 PM 23624716 ER PT J AU Rani, CSS Soto-Pina, A Iacovitti, L Strong, R AF Rani, C. S. Sheela Soto-Pina, Alexandra Iacovitti, Lorraine Strong, Randy TI Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AP-1; glucocorticoid receptor; glucocorticoid response element; tyrosine hydroxylase ID TRANSCRIPTIONAL REGULATION; DNA-BINDING; CYCLIC-AMP; IN-VIVO; RECEPTOR; PROMOTER; AP-1; EXPRESSION; REPRESSION; SEQUENCES AB The human tyrosine hydroxylase (hTH) gene has a 42bp evolutionarily conserved region designated (CR) II at -7.24kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH-CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7bp 5-TGACTAA at -7243bp completely abolished the Dex-stimulated Luc activity of hTH-CRII construct. The AP-1 agonist, tetradeconoyl-12,13-phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP-1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid-responsive element in a 7bp AP-1-like motif in the promoter region at -7.24kb of the human TH gene. C1 [Rani, C. S. Sheela; Soto-Pina, Alexandra; Strong, Randy] UTHSCSA, Dept Pharmacol, San Antonio, TX 78229 USA. [Rani, C. S. Sheela; Soto-Pina, Alexandra; Strong, Randy] UTHSCSA, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Iacovitti, Lorraine] Thomas Jefferson Univ, Dept Neurosci, Farber Inst Neurosci, Philadelphia, PA 19107 USA. [Strong, Randy] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Rani, CSS (reprint author), UTHSCSA, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kadapakkam@uthscsa.edu OI Soto Pina, Alexandra Estela/0000-0002-3289-5510 FU Department of Veterans Affairs [VA 1 I01 BX001641]; Department of Defense [W81XWH-08-02-0118] FX We are grateful to Dr. N. Elango for his helpful suggestions in cloning of the hTH constructs. We thank Dr. John Cidlowski, NIEHS, Research Triangle Park, NC, for his gift of the pCMV5-hGR expression vector. This study was supported in part by grants from the Merit Review Medical Research Program of the Department of Veterans Affairs (VA 1 I01 BX001641; RS) and by the Department of Defense Congressionally Directed Medical Research Program (W81XWH-08-02-0118; RS). The authors have no conflict of interest to declare. NR 36 TC 2 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2013 VL 126 IS 1 BP 19 EP 28 DI 10.1111/jnc.12294 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 168RG UT WOS:000320722700003 ER PT J AU Slavin-Mulford, J Sinclair, SJ Malone, J Stein, M Bello, I Blais, MA AF Slavin-Mulford, Jenelle Sinclair, Samuel Justin Malone, Johanna Stein, Michelle Bello, Iruma Blais, Mark A. TI External Correlates of the Personality Assessment Inventory Higher Order Structures SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID CLINICAL RC SCALES; PSYCHOPATHOLOGY; SAMPLE; PAI AB This brief report explores the external correlates of 2 higher order structures of the Personality Assessment Inventory (PAI; Morey, 1991, 2007); Hoelzle and Meyer's (2009a, 2009b) PAI Components and Hopwood and Moser's (2011) Internalizing and Externalizing Dimensions. Scores from these higher order structures were correlated with life-event data including education, marital status, employment, suicide attempts, psychiatric hospitalizations, trauma, medical problems, hallucinations, paranoid ideation, drug abuse, alcohol abuse, and arrest. Although some differences were noted, the results showed that both Hoelzle and Meyer's Components and Hopwood and Moser's Dimensions were meaningfully correlated with a wide range of life outcomes in a conceptually consistent manner. Overall, these findings provide support for the utility of these higher order variables. C1 [Slavin-Mulford, Jenelle] Augusta State Univ, Dept Psychol, Augusta, GA USA. [Sinclair, Samuel Justin; Malone, Johanna; Stein, Michelle; Blais, Mark A.] Massachusetts Gen Hosp, PEaRL, Boston, MA 02114 USA. [Sinclair, Samuel Justin; Malone, Johanna; Stein, Michelle; Blais, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bello, Iruma] NYU, Langone Med Ctr, Bellevue Hosp, Dept Psychiat, New York, NY 10003 USA. RP Slavin-Mulford, J (reprint author), Georgia Regents Univ, Dept Psychol, 2500 Walton Way, Augusta, GA 30904 USA. EM jslavinm@gru.edu NR 14 TC 1 Z9 1 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JUL 1 PY 2013 VL 95 IS 4 BP 432 EP 434 DI 10.1080/00223891.2013.767820 PG 3 WC Psychology, Clinical; Psychology, Social SC Psychology GA 160EG UT WOS:000320099200012 PM 23437922 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI Preoperative carcinoembryonic antigen as an outcome predictor in colon cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE carcinoembryonic antigen; colon cancer; prognosis; confounders; outcomes ID COLORECTAL-CANCER; LEVEL; CEA; RECURRENCE AB Objective Several reports have shown that certain pre-operative CEA intervals can be predictive of long-term outcomes and have subsequently implied that preoperative CEA may be useful to assess the risk of recurrence or death as a continuous number for individual cases. This analysis assesses if this hypothesis is valid after correction for confounders. Methods All colon cancer patients operated on at Massachusetts General Hospital from 2004 through 2011 were considered for retrospective review. Association between outcomes and preoperative CEA was measured in intervals and as a linear relationship. Results Of the 1,071 patients operated for colon adenocarcinoma, 621 (57.9%) had a preoperative CEA drawn and were included in the analysis. In models using intervals, preoperative CEA did show association with (disease-free) survival, but this was shown to be chiefly a surrogate for metastatic presentation. In linear approaches adjusted for metastatic presentation, CEA loses all correlations with metastatic disease (P=0.84), survival (P=0.11), survival duration (P=0.42) and disease-free interval (P=0.94). Conclusions Extrapolating the predictive value of certain preoperative CEA intervals to a continuous approach for use in a case-for-case basis is unjustified. Preoperative CEA may be a useful risk estimator but has limited significance for predictions of long-term outcomes in individual cases. J. Surg. Oncol. 2013;108:14-18. (c) 2013 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Div Gen Surg & Gastrointestinal Surg, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen Surg & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM berger.david@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU Fulbright Foundation; Harvard Catalyst \ The Harvard Clinical and Translational Science Center; Dutch Cancer Society; Dutch Digestive Society; Amsterdam University FX Grant sponsor: The Fulbright Foundation, Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center, the Dutch Cancer Society, the Dutch Digestive Society, and the Amsterdam University Funds NR 15 TC 12 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUL PY 2013 VL 108 IS 1 BP 14 EP 18 DI 10.1002/jso.23352 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 168SI UT WOS:000320725600003 PM 23681672 ER PT J AU Adamovich, Y Shlomai, A Tsvetkov, P Umansky, KB Reuven, N Estall, JL Spiegelman, BM Shaul, Y AF Adamovich, Yaarit Shlomai, Amir Tsvetkov, Peter Umansky, Kfir B. Reuven, Nina Estall, Jennifer L. Spiegelman, Bruce M. Shaul, Yosef TI The Protein Level of PGC-1 alpha, a Key Metabolic Regulator, Is Controlled by NADH-NQO1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1; 20S PROTEASOMAL DEGRADATION; NAD(P)H-QUINONE OXIDOREDUCTASE-1 NQO1; INTRINSICALLY UNSTRUCTURED PROTEINS; NAD(P)H QUINONE OXIDOREDUCTASE-1; INDUCED SKIN-CANCER; SKELETAL-MUSCLE; HEPATIC GLUCONEOGENESIS; ENERGY-METABOLISM; REDOX STATE AB xPGC-1 alpha is a key transcription coactivator regulating energy metabolism in a tissue-specific manner. PGC-1 alpha expression is tightly regulated, it is a highly labile protein, and it interacts with various proteins-the known attributes of intrinsically disordered proteins (IDPs). In this study, we characterize PGC-1 alpha as an IDP and demonstrate that it is susceptible to 20S proteasomal degradation by default. We further demonstrate that PGC-1 alpha degradation is inhibited by NQO1, a 20S gatekeeper protein. NQO1 binds and protects PGC-1 alpha from degradation in an NADH-dependent manner. Using different cellular physiological settings, we also demonstrate that NQO1-mediated PGC-1 alpha protection plays an important role in controlling both basal and physiologically induced PGC-1 alpha protein level and activity. Our findings link NQO1, a cellular redox sensor, to the metabolite-sensing network that tunes PGC-1 alpha expression and activity in regulating energy metabolism. C1 [Adamovich, Yaarit; Shlomai, Amir; Tsvetkov, Peter; Umansky, Kfir B.; Reuven, Nina; Shaul, Yosef] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Estall, Jennifer L.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Estall, Jennifer L.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA. RP Shaul, Y (reprint author), Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. EM yosef.shaul@weizmann.ac.il FU United States-Israel Binational Science Foundation [2007285]; Israel Science Foundation [551/11]; EMBO short-term fellowship FX This study was supported by grant 2007285 from the United States-Israel Binational Science Foundation and by grants from the Israel Science Foundation (grant 551/11). Y.S. is the Oscar and Emma Getz Professor. Y.A. was supported by an EMBO short-term fellowship (2009). NR 77 TC 14 Z9 14 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2013 VL 33 IS 13 BP 2603 EP 2613 DI 10.1128/MCB.01672-12 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 159FN UT WOS:000320030900008 PM 23648480 ER PT J AU Heidt, T Nahrendorf, M AF Heidt, Timo Nahrendorf, Matthias TI Multimodal iron oxide nanoparticles for hybrid biomedical imaging SO NMR IN BIOMEDICINE LA English DT Review DE nanoparticle; iron oxide; multimodality; multiscale; molecular imaging; MRI; PET; optical imaging ID CARDIAC ALLOGRAFT-REJECTION; OXIDATION-SPECIFIC EPITOPES; ABDOMINAL AORTIC-ANEURYSM; MRI CONTRAST AGENT; IN-VIVO TRACKING; MAGNETIC-RESONANCE; SUPERPARAMAGNETIC PARTICLES; MYOCARDIAL-INFARCTION; QUANTUM DOTS; ATHEROSCLEROTIC PLAQUES AB Iron oxide core nanoparticles are attractive imaging agents because their material properties allow the tuning of pharmacokinetics as well as the attachment of multiple moieties to their surface. In addition to affinity ligands, these include fluorochromes and radioisotopes for detection with optical and nuclear imaging. As the iron oxide core can be detected by MRI, options for combining imaging modalities are manifold. Already, preclinical imaging strategies have combined noninvasive imaging with higher resolution techniques, such as intravital microscopy, to gain unprecedented insight into steady-state biology and disease. Going forward, hybrid iron oxide nanoparticles will help to merge modalities, creating a synergy that will enable imaging in basic research and, potentially, also in the clinic. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Heidt, Timo; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Heidt, Timo; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. RP Nahrendorf, M (reprint author), Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU National Institutes of Health (NIH) [R01HL095629, R01HL096576, HHSN268201000044C]; Deutsche Forschungsgemeinschaft (DFG) [HE6382/1-1] FX This work was funded in part by grants from the National Institutes of Health (NIH) (R01HL095629, R01HL096576, Translational Program of Excellence in Nanotechnology HHSN268201000044C) and Deutsche Forschungsgemeinschaft (DFG) (HE6382/1-1). NR 129 TC 11 Z9 11 U1 2 U2 69 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD JUL PY 2013 VL 26 IS 7 SI SI BP 756 EP 765 DI 10.1002/nbm.2872 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 168UC UT WOS:000320730300005 PM 23065771 ER PT J AU Hussain, M Javeed, A Ashraf, M Hou, YZ Mukhtar, MM AF Hussain, Muzammal Javeed, Aqeel Ashraf, Muhammad Hou Yuzhu Mukhtar, Muhammad Mahmood TI Multilevel pharmacological manipulation of adenosine-prostaglandin E-2/cAMP nexus in the tumor microenvironment: A 'two hit' therapeutic opportunity SO PHARMACOLOGICAL RESEARCH LA English DT Review DE Ectonucleotidases; Adenosine; COX2; PGE(2); Chemo-immunotherapy; cAMP-PKA pathway ID REGULATORY T-CELLS; BREAST-CANCER CELLS; PROTEIN-KINASE-A; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ENDOTHELIAL GROWTH-FACTOR; RESPONSE ELEMENT ACTIVATION; NITRIC-OXIDE DONORS; CYTOKINE PRODUCTION; CYTOTOXIC ACTIVITY; IMMUNE-RESPONSES AB Novel trends in cancer treatment research are focused on targeting the tumor microenvironment, thereby developing chemo-immunotherapeutic strategies which not only directly kill tumor cells, but also trigger the anti-tumor immune effector responses. Ectonucleotidases (CD39 and CD73)-generated extracellular adenosine and cyclooxygenase-2 (COX2)-derived prostaglandin E-2 (PGE(2)) are amongst the tumor microenvironmental factors that have emerged as attractive targets in this regard. Both comprise a pivotal axis in tumor progression and immune escape via autocrine and paracrine activation of a common intracellular signaling pathway, the cAMP-protein kinase A (PKA) pathway, in cancer and immune cells. In this review, we venture a potential and realistic strategy that this adenosine-PGE(2)/cAMP nexus is targetable at different levels, thereby pointing out a 'two hit' chemo-immunotherapeutic proposition: direct killing of tumor cells on one hand, and the rescuing of endogenous anti-tumor immune response on the other. The reviewed experimental, preclinical and clinical data provide the proof of concept that 'two hit' multilevel pharmacological manipulation of adenosine-PGE2/cAMP nexus is achievable within the tumor microenvironment. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hussain, Muzammal; Javeed, Aqeel; Ashraf, Muhammad] Univ Vet & Anim Sci, Dept Pharmacol & Toxicol, Lahore 54600, Pakistan. [Hou Yuzhu] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Transplantat Biol Res Div, Beijing 100101, Peoples R China. [Mukhtar, Muhammad Mahmood] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Javeed, A (reprint author), Univ Vet & Anim Sci, Dept Pharmacol & Toxicol, Abdul Qadir Jilani Rd, Lahore 54600, Pakistan. EM aqeelvet@hotmail.com OI Hussain, Muzammal/0000-0002-1117-5864 NR 137 TC 3 Z9 3 U1 3 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JUL PY 2013 VL 73 BP 8 EP 19 DI 10.1016/j.phrs.2013.04.006 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169AX UT WOS:000320750400002 PM 23619528 ER PT J AU Kuppens, P Tuerlinckx, F Russell, JA Barrett, LF AF Kuppens, Peter Tuerlinckx, Francis Russell, James A. Barrett, Lisa Feldman TI The Relation Between Valence and Arousal in Subjective Experience SO PSYCHOLOGICAL BULLETIN LA English DT Article DE valence; arousal; pleasure; structure of affect; structure of emotion ID EMOTIONAL SELF-REPORT; INDIVIDUAL-DIFFERENCES; CORE AFFECT; PSYCHOLOGICAL CONSTRUCTION; CIRCUMPLEX STRUCTURE; FACIAL EXPRESSIONS; BRAIN MECHANISMS; EVALUATIVE SPACE; MODEL SELECTION; MORAL JUDGMENT/ AB Affect is basic to many if not all psychological phenomena. This article examines 2 of the most fundamental properties of affective experience-valence and arousal-asking how they are related to each other on a moment to moment basis. Over the past century, 6 distinct types of relations have been suggested or implicitly presupposed in the literature. We critically review the available evidence for each proposal and argue that the evidence does not provide a conclusive answer. Next, we use statistical modeling to verify the different proposals in 8 data sets (with Ns ranging from 80 to 1,417) where participants reported their affective experiences in response to experimental stimuli in laboratory settings or as momentary or remembered in natural settings. We formulate 3 key conclusions about the relation between valence and arousal: (a) on average, there is a weak but consistent V-shaped relation of arousal as a function of valence, but (b) there is large variation at the individual level, so that (c) valence and arousal can in principle show a variety of relations depending on person or circumstances. This casts doubt on the existence of a static, lawful relation between valence and arousal. The meaningfulness of the observed individual differences is supported by their personality and cultural correlates. The malleability and individual differences found in the structure of affect must be taken into account when studying affect and its role in other psychological phenomena. C1 [Kuppens, Peter; Tuerlinckx, Francis] Katholieke Univ Leuven, Fac Psychol & Educ Sci, B-3000 Louvain, Belgium. [Kuppens, Peter] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, Vic, Australia. [Russell, James A.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Kuppens, P (reprint author), Katholieke Univ Leuven, Fac Psychol & Educ Sci, Tiensestr 102,Box 3713, B-3000 Louvain, Belgium. EM peter.kuppens@ppw.kuleuven.be FU KU Leuven Research Council [GOA/10/02, OT/11/031]; Fund for Scientific Research-Flanders [G.0534.09N, G.0935.12]; National Institutes of Health [DP1OD003312]; National Science Foundation FX Preparation of this article was supported by KU Leuven Research Council Grants GOA/10/02 and OT/11/031, the Fund for Scientific Research-Flanders (Grants G.0534.09N and G.0935.12), the National Institutes of Health Director's Pioneer Award (DP1OD003312) to Lisa Feldman Barrett, and a grant from the National Science Foundation to James A. Russell. We thank Nick Has lam, Yoshi Kashima, and Batja Mesquita for comments on an earlier version of this article. NR 150 TC 56 Z9 57 U1 11 U2 77 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD JUL PY 2013 VL 139 IS 4 BP 917 EP 940 DI 10.1037/a0030811 PG 24 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 170GL UT WOS:000320838300008 PM 23231533 ER PT J AU Greve, DN Brown, GG Mueller, BA Glover, G Liu, TT AF Greve, Douglas N. Brown, Gregory G. Mueller, Bryon A. Glover, Gary Liu, Thomas T. TI A SURVEY OF THE SOURCES OF NOISE IN FMRI SO PSYCHOMETRIKA LA English DT Article DE functional MRI; blood oxygen level dependent; first-level analysis; higher level analysis; sources of noise ID EVENT-RELATED FMRI; INDEPENDENT COMPONENT ANALYSIS; MULTICENTER FUNCTIONAL MRI; BOLD HEMODYNAMIC-RESPONSES; MAGNETIC-RESONANCE; PHYSIOLOGICAL NOISE; TIME-SERIES; STATISTICAL-ANALYSIS; IMAGE REGISTRATION; HUMAN BRAIN AB Functional magnetic resonance imaging (fMRI) is a noninvasive method for measuring brain function by correlating temporal changes in local cerebral blood oxygenation with behavioral measures. fMRI is used to study individuals at single time points, across multiple time points (with or without intervention), as well as to examine the variation of brain function across normal and ill populations. fMRI may be collected at multiple sites and then pooled into a single analysis. This paper describes how fMRI data is analyzed at each of these levels and describes the noise sources introduced at each level. C1 [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Brown, Gregory G.] Univ Calif San Diego, VA San Diego Healthcare Syst, La Jolla, CA 92093 USA. [Brown, Gregory G.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Mueller, Bryon A.] Univ Minnesota Twin Cities, Dept Psychiat, St Paul, MN USA. [Glover, Gary] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Liu, Thomas T.] Univ Calif San Diego, Ctr Funct MRI, La Jolla, CA 92093 USA. RP Greve, DN (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM greve@nmr.mgh.harvard.edu FU National Center for Research Resources [P41-RR14075, R01 RR16594, P41-009874]; National Center for Research Resources (NCRR BIRN Morphometric Project) [BIRN002]; National Center for Research Resources (Functional Imaging Biomedical Informatics Research Network (FBIRN)) [U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550, R01EB006758]; Department of Energy [DE-F02-99ER62764-A012] FX Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, R01 RR16594, P41-009874, the NCRR BIRN Morphometric Project BIRN002, and Functional Imaging Biomedical Informatics Research Network (FBIRN) U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01EB006758), as well as by the Department of Energy (DE-F02-99ER62764-A012) to the Mind Research Network (previously known as the MIND Institute). NR 84 TC 10 Z9 10 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3123 J9 PSYCHOMETRIKA JI Psychometrika PD JUL PY 2013 VL 78 IS 3 BP 396 EP 416 DI 10.1007/S11336-012-9294-0 PG 21 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematics; Mathematical Methods In Social Sciences; Psychology GA 164XT UT WOS:000320446500001 PM 25106392 ER PT J AU Van Eylen, L De Graef, P Steyaert, J Wagemans, J Noens, I AF Van Eylen, Lien De Graef, Peter Steyaert, Jean Wagemans, Johan Noens, Ilse TI Children with autism spectrum disorder spontaneously use scene knowledge to modulate visual object processing SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Weak central coherence; Context effects; Scene perception; Eye-movements ID WEAK COHERENCE; CONTEXT; RECOGNITION; PERCEPTION; IDENTIFICATION; ATTENTION; FIXATION; PEOPLE; ADULTS; SPEED AB Several studies have investigated contextual influences on visual object processing in individuals with autism spectrum disorder (ASD) and failed to find reduced context effects. However, these studies did not properly account for local inter-object effects and/or the influence of post-perceptual processes, leaving it unclear whether individuals with ASD display equally large global top-down effects of context, or whether they rely on a more local mechanism producing the same result. In this study, an eye-movement paradigm was used to investigate implicitly induced context effects on visual object processing in children with ASD compared to matched controls. To find out whether the context effects in the ASD group were, to the same extent, due to early top-down influences on object recognition, we also examined the interaction between context effects and the ease of object recognition. Both groups displayed equally large context effects and congruent contextual information facilitated object recognition to the same extent in both groups. This indicates that the context effects in the ASD group did not result from the operation of a more local, less top-down mechanism. These findings contradict predictions based on the weak central coherence account. However, a good alternative to explain all inconsistencies is currently lacking. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Van Eylen, Lien; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Louvain, Belgium. [Van Eylen, Lien; Steyaert, Jean; Wagemans, Johan; Noens, Ilse] Katholieke Univ Leuven, Leuven Autism Res, Louvain, Belgium. [Van Eylen, Lien; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Louvain, Belgium. [De Graef, Peter; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, Louvain, Belgium. [De Graef, Peter] Thomas More Univ Coll, Dept Appl Psychol, Antwerp, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Van Eylen, L (reprint author), Univ Hosp Leuven, Dept Child Psychiat, Herestr 49 Box 7003, B-3000 Louvain, Belgium. EM Lien.VanEylen@ped.kuleuven.be RI Steyaert, Jean/B-5326-2015 OI Steyaert, Jean/0000-0003-2512-4694 NR 35 TC 2 Z9 2 U1 2 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JUL PY 2013 VL 7 IS 7 BP 913 EP 922 DI 10.1016/j.rasd.2013.04.005 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 159TM UT WOS:000320070200011 ER PT J AU Biederman, J Petty, CR Spencer, TJ Woodworth, KY Bhide, P Zhu, J Faraone, SV AF Biederman, J. Petty, C. R. Spencer, T. J. Woodworth, K. Y. Bhide, P. Zhu, J. Faraone, S. V. TI Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post-traumatic stress disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE attention deficit disorder (ADD); attention deficit; hyperactivity disorder (ADHD); post-traumatic stress disorder (PTSD); comorbidity ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; MAJOR DEPRESSION; ADHD; CHILDREN; MEN AB Biederman J, Petty CR, Spencer TJ, Woodworth KY, Bhide P, Zhu J, Faraone SV. Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post-traumatic stress disorder. Objective: This study sought to address the link between attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) in youth by providing a comprehensive comparison of clinical correlates of ADHD subjects with and without PTSD across multiple non-overlapping domains of functioning and familial patterns of transmission. Method: Participants were 271 youths with ADHD and 230 controls without ADHD of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric comorbidity, psychosocial, educational, and cognitive parameters. Results: Post-traumatic stress disorder was significantly higher in ADHD probands vs. controls (5.2% vs. 1.7%, 2(1)=4.36, P=0.04). Irrespective of the comorbidity with PTSD, ADHD subjects had similar ages at onset of ADHD, similar type and mean number of ADHD symptoms, and similar ADHD-associated impairments. PTSD in ADHD probands was significantly associated with a higher risk of psychiatric hospitalization, school impairment, poorer social functioning and higher prevalences of mood, conduct disorder, and anxiety disorders. The mean onset of PTSD (12.6years) was significantly later than that of ADHD and comorbid disorders (all P<0.05). Siblings of ADHD and ADHD+PTSD probands had higher prevalences of ADHD vs. siblings of controls (35% vs. 18%, z=4.00, P<0.001 and 67% vs. 18%, z=4.02, P<0.001 respectively) and siblings of ADHD+PTSD probands had a significantly higher prevalence of PTSD compared with the siblings of ADHD and control probands (20% vs. 3% and 3%, z=2.99, P=0.003 and z=2.07, P=0.04 respectively). Conclusion: Findings indicate that the comorbidity with PTSD in ADHD leads to greater clinical severity as regards psychiatric comorbidity and psychosocial dysfunction. ADHD is equally familial in the presence of PTSD in the proband indicating that their co-occurrence is not owing to diagnostic error. C1 [Biederman, J.; Petty, C. R.; Spencer, T. J.; Woodworth, K. Y.] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA. [Biederman, J.; Spencer, T. J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Bhide, P.; Zhu, J.] Florida State Univ, Dept Biomed Sci, Coll Med, Tallahassee, FL 32306 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Clin & Res Programs Pediat Psychopharmacol & Adul, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Bhide, Pradeep/0000-0003-4236-9415; Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Health [R01 HD36317, R01 MH50657]; Pediatric Psychopharmacology Research Council FX This manuscript was supported in part by grants to J. Biederman from the National Institute of Health (R01 HD36317, R01 MH50657) and the Pediatric Psychopharmacology Research Council Fund. NR 25 TC 9 Z9 10 U1 0 U2 24 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 JUL PY 2013 VL 128 IS 1 BP 78 EP 87 DI 10.1111/acps.12011 PG 10 WC Psychiatry SC Psychiatry GA 160PZ UT WOS:000320133000009 PM 22985097 ER PT J AU Williams, FMK Bansal, AT van Meurs, JB Bell, JT Meulenbelt, I Suri, P Rivadeneira, F Sambrook, PN Hofman, A Bierma-Zeinstra, S Menni, C Kloppenburg, M Slagboom, PE Hunter, DJ MacGregor, AJ Uitterlinden, AG Spector, TD AF Williams, Frances M. K. Bansal, Aruna T. van Meurs, Joyce B. Bell, Jordana T. Meulenbelt, Ingrid Suri, Pradeep Rivadeneira, Fernando Sambrook, Philip N. Hofman, Albert Bierma-Zeinstra, Sita Menni, Cristina Kloppenburg, Margreet Slagboom, P. Eline Hunter, David J. MacGregor, Alex J. Uitterlinden, Andre G. Spector, Tim D. TI Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID GENOME-WIDE ASSOCIATION; RADIOGRAPHIC FEATURES; HAND OSTEOARTHRITIS; MAGNETIC-RESONANCE; CANDIDATE GENES; GENOTYPE DATA; BACK-PAIN; BODY-MASS; SPINE; DISEASE AB Objective Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD. Methods We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2. Results This study of 4600 individuals identified four single nucleotide polymorphisms with p<5x10(-8), the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8x10(-8)) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (beta=8.74x10(-4), p=0.006). Conclusions LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway. C1 [Williams, Frances M. K.; Bell, Jordana T.; Menni, Cristina; MacGregor, Alex J.; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Bansal, Aruna T.] Acclarogen Ltd, St Johns Innovat Ctr, Cambridge, England. [van Meurs, Joyce B.; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [van Meurs, Joyce B.; Meulenbelt, Ingrid; Rivadeneira, Fernando; Slagboom, P. Eline] NCHA, NGI, Leiden, Netherlands. [Meulenbelt, Ingrid; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Suri, Pradeep] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Spaulding Rehabil Hosp,New England Baptist Hosp, Boston, MA USA. [Sambrook, Philip N.; Hunter, David J.] Univ Sydney, Dept Rheumatol, Sydney, NSW 2006, Australia. [Sambrook, Philip N.; Hunter, David J.] Royal N Shore Hosp, Sydney, NSW, Australia. [Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Bierma-Zeinstra, Sita] Erasmus MC, Dept Gen Practice, Rotterdam, Netherlands. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands. RP Williams, FMK (reprint author), Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, Westminster Bridge Rd, London SE1 7EH, England. EM frances.williams@kcl.ac.uk RI Rivadeneira, Fernando/O-5385-2015; Slagboom, P. Eline/R-4790-2016; OI Rivadeneira, Fernando/0000-0001-9435-9441; Slagboom, P. Eline/0000-0002-2875-4723; Menni, Cristina/0000-0001-9790-0571; Williams, Frances/0000-0002-2998-2744; MacGregor, Alex/0000-0003-2163-2325 FU Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/the Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organisation for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; Leiden University Medical Centre; Dutch Arthritis Association; Pfizer Inc., Groton, CT, USA; Netherlands Organisation of Scientific Research [911-03-012, MW 904-61-095, 911-03-016, 917 66344]; Centre of Medical System Biology; Netherlands Consortium for Healthy Aging both in the framework of the Netherlands Genomics Initiative (NGI); European Union's Seventh Framework Programme [259679]; National Institute of Health (US) [K12HD01097]; Rehabilitation Medicine Scientist Training Programme (RMSTP); National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195] FX FMKW is a Wellcome Trust Intermediate Fellow. The authors would like to acknowledge the contribution of Maria Popham to the collection and analysis of TwinsUK data. The GWA study was funded by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2) and the Netherlands Genomics Initiative (NGI)/the Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Dr Michael Moorhouse, Marijn Verkerk and Sander Bervoets for their help in creating the GWAS database. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands Organisation for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are very grateful to the participants and staff from the Rotterdam Study, the participating general practitioners and the pharmacists. We would like to thank Dr Tobias A Knoch, Luc V de Zeeuw, Anis Abuseiris and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology under grants #01 AK 803 A-H and #01 IG 07015 G for access to their grid resources. The GARP study was supported by the Leiden University Medical Centre and the Dutch Arthritis Association. Pfizer Inc., Groton, CT, USA supported the inclusion of the GARP study. The genotypic work was supported by the Netherlands Organisation of Scientific Research (MW 904-61-095, 911-03-016, 917 66344 and 911-03-012), Leiden University Medical Centre and the Centre of Medical System Biology and the Netherlands Consortium for Healthy Aging both in the framework of the Netherlands Genomics Initiative (NGI). The research leading to these studies has received funding from the European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement no 259679. Pradeep Suri was funded by K12HD01097 from the National Institute of Health (US) and the Rehabilitation Medicine Scientist Training Programme (RMSTP). The Framingham Study is supported by the National Heart, Lung and Blood Institute's Framingham Heart Study contract (No. N01-HC-25195) for the recruitment, enrolment and examination of the Offspring and Third Generation cohorts and the imaging by CT scan. NR 49 TC 19 Z9 21 U1 2 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2013 VL 72 IS 7 BP 1141 EP 1148 DI 10.1136/annrheumdis-2012-201551 PG 8 WC Rheumatology SC Rheumatology GA 155GX UT WOS:000319737000012 PM 22993228 ER PT J AU Li, WQ Han, JL Chan, AT Qureshi, AA AF Li, Wen-Qing Han, Jia-Li Chan, Andrew T. Qureshi, Abrar A. TI Psoriasis, psoriatic arthritis and increased risk of incident Crohn's disease in US women SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS; SUSCEPTIBILITY LOCI; GENE; EPIDEMIOLOGY; SMOKING; COMORBIDITIES; QUESTIONNAIRE; PATHOGENESIS AB Objective Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), shares clinical and immunological features with psoriasis. Genome-wide association studies have found common susceptibility genes. However, epidemiologic data evaluating the association between psoriasis, psoriatic arthritis and risk of IBD are sparse. We aimed to evaluate the association between psoriasis, psoriatic arthritis and incident CD and UC among women in the USA. Methods 174 476 women were enrolled in the Nurses' Health Study (NHS) (1996-2008) and NHS II (1991-2007). Lifetime history of physician-diagnosed psoriasis and psoriatic arthritis was confirmed by supplementary questionnaires. Information on CD and UC was obtained by self-reported questionnaires and confirmed by medical record review. Results We documented 188 incident cases of CD and 240 incident cases of UC during follow-up. Psoriasis was associated with a significantly increased risk of subsequent CD with a multivariate-adjusted relative risk (RR) of 4.00 (95% CI 1.72 to 9.27) for NHS and 3.76 (1.82 to 7.74) for NHS II. By contrast, we did not observe a significant increase in risk of UC associated with psoriasis. In a pooled analysis of both cohorts, women with psoriasis experienced a significantly increased risk of CD (RR, 3.86, 95% CI 2.23 to 6.67), but not UC (RR, 1.17, 95% CI 0.41 to 3.36). The risk of CD was especially pronounced among psoriatics with concomitant psoriatic arthritis (RR, 6.43, 95% CI 2.04 to 20.32). Conclusions Psoriasis with concomitant psoriatic arthritis is associated with an increased risk of incident CD. C1 [Li, Wen-Qing; Han, Jia-Li; Qureshi, Abrar A.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Li, Wen-Qing; Han, Jia-Li; Chan, Andrew T.; Qureshi, Abrar A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Han, Jia-Li; Chan, Andrew T.; Qureshi, Abrar A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Han, Jia-Li] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Qureshi, AA (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Sch Med, 45 Francis St,221L, Boston, MA 02115 USA. EM achan@partners.org; aqureshi@bics.bwh.harvard.edu RI Li, Wenqing/N-2293-2014 OI Li, Wenqing/0000-0002-1283-4091 FU Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts; Nurses' Health Study grant [P01 CA87969]; Nurses' Health Study II grant [R01 CA50385]; Centre for the Study of Inflammatory Bowel Disease grant [P30 DK043351]; Broad Medical Research Programme of the Broad Foundation FX This work was supported by Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, a Nurses' Health Study grant (P01 CA87969), a Nurses' Health Study II grant (R01 CA50385), a Centre for the Study of Inflammatory Bowel Disease grant (P30 DK043351), and the Broad Medical Research Programme of the Broad Foundation. The funding sources did not involve in the data collection, data analysis, manuscript writing and publication. NR 45 TC 42 Z9 44 U1 0 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2013 VL 72 IS 7 BP 1200 EP 1205 DI 10.1136/annrheumdis-2012-202143 PG 6 WC Rheumatology SC Rheumatology GA 155GX UT WOS:000319737000021 PM 22941766 ER PT J AU Trinh, QD AF Quoc-Dien Trinh TI Why I care about social media - and why you should too SO BJU INTERNATIONAL LA English DT Editorial Material C1 [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUL PY 2013 VL 112 IS 1 BP 1 EP 2 DI 10.1111/bju.12270 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 161NC UT WOS:000320198900003 PM 23759002 ER PT J AU Carrera, S Cuadrado-Castano, S Samuel, J Jones, GDD Villar, E Lee, SW Macip, S AF Carrera, S. Cuadrado-Castano, S. Samuel, J. Jones, G. D. D. Villar, E. Lee, S. W. Macip, S. TI Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; p53; reactive oxygen species; retinoic acid; Stra6 ID BINDING-PROTEIN RECEPTOR; CELL FATE DECISIONS; VITAMIN-A; SYNERGISTIC INDUCTION; P53 PATHWAY; EXPRESSION; CANCER; SENESCENCE; STRESS; OVEREXPRESSION AB Stra6 is the retinoic acid (RA)-inducible gene encoding the cellular receptor for holo-retinol binding protein. This transmembrane protein mediates the internalization of retinol, which then upregulates RA-responsive genes in target cells. Here, we show that Stra6 can be upregulated by DNA damage in a p53-dependent manner, and it has an important role in cell death responses. Stra6 expression induced significant amounts of apoptosis in normal and cancer cells, and it was also able to influence p53-mediated cell fate decisions by turning an initial arrest response into cell death. Moreover, inhibition of Stra6 severely compromised p53-induced apoptosis. We also found that Stra6 induced mitochondria depolarization and accumulation of reactive oxygen species, and that it was present not only at the cellular membrane but also in the cytosol. Finally, we show that these novel functions of Stra6 did not require downstream activation of RA signalling. Our results present a previously unknown link between the RA and p53 pathways and provide a rationale to use retinoids to upregulate Stra6, and thus enhance the tumour suppressor functions of p53. This may have implications for the role of vitamin A metabolites in cancer prevention and treatment. C1 [Carrera, S.; Samuel, J.; Macip, S.] Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England. [Cuadrado-Castano, S.; Villar, E.] Univ Salamanca, Dept Biochem & Mol Biol, E-37008 Salamanca, Spain. [Jones, G. D. D.] Univ Leicester, Dept Canc Studies & Mol Med, Leicester LE1 9HN, Leics, England. [Lee, S. W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, S. W.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Macip, S (reprint author), Univ Leicester, Dept Biochem, Lancaster Rd, Leicester LE1 9HN, Leics, England. EM sm460@le.ac.uk RI Macip, Salvador/K-5985-2014 FU MRC; CONACYT [200721]; European Union (ECNIS); Hope Against Cancer; Cancer Research UK; Junta de Castilla y Leon, Consejeria de Educacion; Fondo de Investigaciones Sanitarias (FIS) from the Spanish Government [PI08/1813] FX We thank S A Aaronson for his help in the initial stages of this project. We thank S Cowley and M J Dyer for useful discussions and critical reading of the manuscript. We also thank K Straatman and the Advanced Image Facilities for assistance with immunofluorescence experiments. This work was funded by the MRC (www.mrc.ac.uk, New Blood Lectureship Research Support Funding). S Carrera held a predoctoral fellowship from CONACYT (www.conacyt.mx, fellow no. 200721). Work in the lab of GDDJ is supported by the European Union (ECNIS, www.ecnis.org), Hope Against Cancer (www.hfcr.org) and Cancer Research UK (www.cancerresearchuk.org). S Cuadrado was a predoctoral fellowship holder from Junta de Castilla y Leon, Consejeria de Educacion (www.educa.jcyl.es). This work was also partially supported by grants from Fondo de Investigaciones Sanitarias (FIS, PI08/1813) from the Spanish Government (www.mineco.gob.es/) to E.V. NR 46 TC 10 Z9 11 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUL PY 2013 VL 20 IS 7 BP 910 EP 919 DI 10.1038/cdd.2013.14 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 160EO UT WOS:000320100000011 PM 23449393 ER PT J AU Cahoon, EK Rozhko, A Hatch, M Polyanskaya, O Ostroumova, E Tang, M Nadirov, E Yauseyenka, V Savasteeva, I McConnell, RJ Pfeiffer, RM Brenner, AV AF Cahoon, Elizabeth K. Rozhko, Alexander Hatch, Maureen Polyanskaya, Olga Ostroumova, Evgenia Tang, Min Nadirov, Eldar Yauseyenka, Vasilina Savasteeva, Irina McConnell, Robert J. Pfeiffer, Ruth M. Brenner, Alina V. TI Factors associated with serum thyroglobulin levels in a population living in Belarus SO CLINICAL ENDOCRINOLOGY LA English DT Article ID DIFFERENTIATED THYROID-CANCER; CHERNOBYL ACCIDENT; IODINE DEFICIENCY; HEALTHY-SUBJECTS; MARKER; TG; RADIOIMMUNOASSAY; AUTOANTIBODIES; CARCINOMA; DISEASE AB Objective Serum thyroglobulin (Tg) has been associated with a number of thyroid disorders and has been proposed as an indicator of iodine deficiency in a population. However, few studies have addressed the epidemiology of Tg in a population-based setting or in the context of exposure to radioactive iodine-131 (I-131). Our objective was to evaluate baseline levels of Tg in relation to sociodemographic characteristics, iodine status and thyroid function for individuals exposed to I-131. Design A population-based cohort assembled in Belarus following the Chornobyl accident provided demographic factors, clinical data and physiological measurements. Participants Our analytical sample included 10344 subjects of whom 7890 had no thyroid disease and 2454 had evidence of structural or functional thyroid abnormality. Measurements Standardized assays were used to measure serum Tg, urinary iodine, TSH and antibodies to Tg and thyroid peroxidase. Ultrasound was used to assess the presence of nodules and estimate thyroid volume. Results In the fully adjusted model, percent change in Tg was significantly increased among females, smokers and subjects of older age and Tg increased with decreasing urinary iodine concentration, increasing serum TSH and increasing thyroid volume (P-values for trend <0 center dot 0001), and presence of thyroid nodules (P<0 center dot 05). We found a complex interaction between region of residence, rural/urban living, presence/absence of thyroid abnormalities and serum Tg (P<0 center dot 0001). Conclusions In residents of Belarus, serum Tg is significantly related to presence of thyroid abnormalities as well as indicators of thyroid function and iodine deficiency and, therefore, could be used to characterize the iodine status and thyroid function of individuals in the context of epidemiological study. C1 [Cahoon, Elizabeth K.; Hatch, Maureen; Ostroumova, Evgenia; Brenner, Alina V.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. [Rozhko, Alexander; Polyanskaya, Olga; Nadirov, Eldar; Yauseyenka, Vasilina; Savasteeva, Irina] Republican Ctr Radiat Med & Human Ecol, Res Dept, Gomel, Byelarus. [Tang, Min] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tang, Min] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Dept Med, Thyroid Ctr, New York, NY USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. RP Cahoon, EK (reprint author), 6120 Execut Blvd,EPS,Room 7053,MSC 7238, Bethesda, MD 20892 USA. EM khaykine@mail.nih.gov FU Intramural NIH HHS [ZIA CP010132-17] NR 35 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 2013 VL 79 IS 1 BP 120 EP 127 DI 10.1111/cen.12107 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 158SP UT WOS:000319993500018 PM 23190420 ER PT J AU Troelsen, A Malchau, E Sillesen, N Malchau, H AF Troelsen, Anders Malchau, Erik Sillesen, Nanna Malchau, Henrik TI A Review of Current Fixation Use and Registry Outcomes in Total Hip Arthroplasty: The Uncemented Paradox SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Review ID CONCISE FOLLOW-UP; SURVIVORSHIP; MINIMUM; CEMENT AB The majority (86%) of THAs performed in the United States are uncemented. This may increase the revision burden if uncemented fixation is associated with a higher risk of revision than other approaches. We sought to investigate trends for use of uncemented fixation and to analyze age-stratified risk of revision comparing cemented, hybrid, and uncemented fixation as reported by national hip arthroplasty registries. Data were extracted from the annual reports of seven national hip arthroplasty registries; we included all national registries for which annual reports were available in English or a Scandinavian language, if the registry had a history of more than 5 years of data collection. Current use of uncemented fixation in primary THAs varies between 15% in Sweden and 82% in Canada. From 2006 to 2010 the registries of all countries reported overall increases in the use of uncemented fixation; Sweden reported the smallest absolute increase (from 10% to 15%), and Denmark reported the greatest absolute increase (from 47% to 68%). Looking only at the oldest age groups, use of uncemented fixation also was increasing during the period. In the oldest age group of each of the registries we surveyed (age older than 65 years for England-Wales; age older than 75 years in three registries), cemented fixation was associated with a lower risk of revision than was uncemented fixation. Increasing use of uncemented fixation in THA is a worldwide phenomenon. This trend is paradoxic, given that registry data, which represent nationwide THA outcomes, suggest that cemented fixation in patients older than 75 years results in the lowest risk of revision. Level II, systematic review. See Guidelines for Authors for a complete description of levels of evidence. C1 [Troelsen, Anders; Malchau, Erik; Sillesen, Nanna; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, Boston, MA 02114 USA. [Troelsen, Anders; Sillesen, Nanna] Copenhagen Univ Hosp, Dept Orthoped, Hvidovre, Denmark. RP Troelsen, A (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM a_troelsen@hotmail.com OI Malchau, Henrik/0000-0002-4291-2441 NR 20 TC 32 Z9 32 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 2013 VL 471 IS 7 BP 2052 EP 2059 DI 10.1007/s11999-013-2941-7 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 159SY UT WOS:000320067400003 PM 23539124 ER PT J AU Kopecky, K Broder-Fingert, S Iannuzzi, D Connors, S AF Kopecky, Kimberly Broder-Fingert, Sarabeth Iannuzzi, Dorothea Connors, Susan TI The Needs of Hospitalized Patients With Autism Spectrum Disorders: A Parent Survey SO CLINICAL PEDIATRICS LA English DT Article DE autism; inpatient; hospitalization; parent; survey ID HEALTH-CARE UTILIZATION; NATIONAL PROFILE; UNITED-STATES; CHILDREN; PAIN; EXPENDITURES; DISABILITIES; INDIVIDUALS; EXPERIENCES; FAMILIES AB Objective. This survey assessed the in-hospital needs of patients diagnosed with autism spectrum disorders (ASDs). Methods. Parents were recruited to complete a 21-item survey about the needs of their child with an ASD while in the hospital. ASD diagnosis was reported by parents at the time of the survey. The results of the survey were analyzed and evaluated in 3 distinct categories of need. Results. We documented a range of responses associated with ASD-specific needs during hospitalization. Common concerns included child safety and the importance of acknowledging individual communication methods. Conclusions. In a population of children with ASDs, parents report a diverse range of needs while in the hospital. These data support the concept that a pragmatic assessment of individual communication and sensory differences is likely to be essential in the development of an appropriate inpatient care plan. C1 [Kopecky, Kimberly; Connors, Susan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Broder-Fingert, Sarabeth] Massachusettes Gen Hosp Children, Boston, MA USA. [Iannuzzi, Dorothea] Harvard Vanguard Med Associates, Simmons Coll Sch Social Work, Boston, MA USA. [Connors, Susan] Massachusetts Gen Hosp, Lexington, MA USA. RP Kopecky, K (reprint author), Harvard Univ, Sch Med, 31 Irving St Apt 10, Boston, MA 02114 USA. EM Kimberly_kopecky@hms.harvard.edu OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 FU MGHfC; Nancy Lurie Marks Family Foundation FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors would like to thank the MGHfC Quality and Safety Executive Team for the small grant used to fund the interdisciplinary autism toolkit, The Nancy Lurie Marks Family Foundation, and Eve Megargel for her help in developing the site-specific photograph book. NR 29 TC 12 Z9 12 U1 3 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JUL PY 2013 VL 52 IS 7 BP 652 EP 660 DI 10.1177/0009922813485974 PG 9 WC Pediatrics SC Pediatrics GA 156IW UT WOS:000319816300012 PM 23624619 ER PT J AU Saadi, I Das, P Zhao, ML Raj, L Ruspita, I Xia, Y Papaioannou, VE Bei, M AF Saadi, Irfan Das, Pragnya Zhao, Minglian Raj, Lakshmi Ruspita, Intan Xia, Yan Papaioannou, Virginia E. Bei, Marianna TI Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development SO DEVELOPMENT LA English DT Article DE Bmp4; Msx1; Tbx2; Protein-protein interaction; Tooth ID EPITHELIAL-MESENCHYMAL INTERACTIONS; BOX GENES; TRANSCRIPTIONAL REPRESSION; HEART DEVELOPMENT; MICE; MORPHOGENESIS; TEETH; ABNORMALITIES; HOMEODOMAIN; DOWNSTREAM AB Bmp4 expression is tightly regulated during embryonic tooth development, with early expression in the dental epithelial placode leading to later expression in the dental mesenchyme. Msx1 is among several transcription factors that are induced by epithelial Bmp4 and that, in turn, are necessary for the induction and maintenance of dental mesenchymal Bmp4 expression. Thus, Msx1(-/-) teeth arrest at early bud stage and show loss of Bmp4 expression in the mesenchyme. Ectopic expression of Bmp4 rescues this bud stage arrest. We have identified Tbx2 expression in the dental mesenchyme at bud stage and show that this can be induced by epithelial Bmp4. We also show that endogenous Tbx2 and Msx1 can physically interact in mouse C3H10T1/2 cells. In order to ascertain a functional relationship between Msx1 and Tbx2 in tooth development, we crossed Tbx2 and Msx1 mutant mice. Our data show that the bud stage tooth arrest in Msx1(-/-) mice is partially rescued in Msx1(-/-);Tbx2(+/-) compound mutants. This rescue is accompanied by formation of the enamel knot (EK) and by restoration of mesenchymal Bmp4 expression. Finally, knockdown of Tbx2 in C3H10T1/2 cells results in an increase in Bmp4 expression. Together, these data identify a novel role for Tbx2 in tooth development and suggest that, following their induction by epithelial Bmp4, Msx1 and Tbx2 in turn antagonistically regulate odontogenic activity that leads to EK formation and to mesenchymal Bmp4 expression at the key bud-to-cap stage transition. C1 [Saadi, Irfan; Das, Pragnya; Zhao, Minglian; Ruspita, Intan; Xia, Yan; Bei, Marianna] Forsyth Inst, Ctr Regenerat & Dev Biol, Cambridge, MA 02142 USA. [Saadi, Irfan] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA. [Raj, Lakshmi] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Papaioannou, Virginia E.] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY USA. [Bei, Marianna] Massachusetts Gen Hosp, Ctr Engn Med, Dept Surg, Boston, MA 02114 USA. [Bei, Marianna] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bei, M (reprint author), Forsyth Inst, Ctr Regenerat & Dev Biol, Cambridge, MA 02142 USA. EM mbei@forsyth.org OI Saadi, Irfan/0000-0002-6250-6651; Papaioannou, Virginia/0000-0001-7558-8601 FU National Institutes of Health (NIH) [NIH/National Institute of Child Health and Human Development (NICHD)] [HD033082]; National Institutes of Health (NIH) [NIH/National Institute of Dental and Craniofacial Research (NIDCR)] [DE019226]; National Institutes of Health (NIH) [NIH/National Institute of General Medical Sciences (NIGMS) IDeA] [P20GM104936] FX This project was supported by the National Institutes of Health (NIH) [NIH/National Institute of Child Health and Human Development (NICHD) MERIT award HD033082 to V.E.P.; NIH/National Institute of Dental and Craniofacial Research (NIDCR) RO1 award DE019226 to M.B.; and NIH/National Institute of General Medical Sciences (NIGMS) IDeA P20GM104936 sub-award to I.S.]. Deposited in PMC for release after 12 months. NR 34 TC 15 Z9 15 U1 0 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL 1 PY 2013 VL 140 IS 13 BP 2697 EP 2702 DI 10.1242/dev.088393 PG 6 WC Developmental Biology SC Developmental Biology GA 161CH UT WOS:000320168300007 PM 23720046 ER PT J AU Berg, AT Caplan, R Baca, CB Vickrey, BG AF Berg, Anne T. Caplan, Rochelle Baca, Christine B. Vickrey, Barbara G. TI Adaptive behavior and later school achievement in children with early-onset epilepsy SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID LONG-TERM PROGNOSIS; CRYPTOGENIC EPILEPSY; DISABILITY; EDUCATION; SEIZURE AB Aim To determine whether early measures of adaptive behavior are predictive of later school difficulties and achievement in otherwise neurotypical (unimpaired) children with onset of epilepsy during the preschool years. Method In a prospective cohort study, parents completed the Vineland Adaptive Behavior Scales (VABS) for children who were aged 5years or less at epilepsy diagnosis. Eight to 9 years later, the children were assessed using the Wechsler Intelligence Scales for Children (WISC), the Wide Range Achievement Test (WRAT), and the Child Behavior Checklist (CBCL). Associations of VABS scores with later WRAT and CBCL scores were tested. Results A total of 108 neurotypical children (64 males, 44 females; mean age at testing 11y 11mo, SD 2y) were studied. After adjustment for IQ and other factors, there was an increase of 0.15 points (95% confidence interval [CI] 0.03-0.27 points; p=0.03) and 0.14 points (95% CI 0.0-0.28 points; p=0.05) in WRAT reading and spelling scores for each 1-point increment in the VABS communication score. Corresponding numbers for the VABS socialization score were 0.20 (95% CI 0.08-0.32; p=0.005) and 0.17 (95% CI 0.05-0.29; p=0.005). Conclusion In neurotypical preschool children with epilepsy, early social and communication scores predict later school performance. These findings raise questions about opportunities for early identification and intervention for children at greatest risk. C1 [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Chicago, IL USA. [Caplan, Rochelle] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Baca, Christine B.; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Baca, Christine B.; Vickrey, Barbara G.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. RP Berg, AT (reprint author), Lurie Childrens Hosp, Epilepsy Ctr, 225 East Chicago Ave,Box 29, Chicago, IL 60611 USA. EM atberg@luriechildrens.org FU NINDS [R37-NS31146]; Pediatric Epilepsy Research Foundation; National Institutes of Health (NIA, NINDS); US Veterans Administration Health Services Research and Development Service; American Heart Association; [NINDS-R37-NS31146]; [NINDS R37 NS31146] FX Dr Berg has received speaker honoraria and travel support from BIAL pharmaceuticals and the Medical University of South Carolina, and travel support from the International League Against Epilepsy. She serves on the editorial boards of Epilepsy & Behavior and Neurology, and is supported by funding from the NINDS (grant R37-NS31146) and the Pediatric Epilepsy Research Foundation. Dr Caplan receives support from grant NINDS-R37-NS31146. She serves on the editorial boards of Epilepsy & Behavior, Epilepsy Currents, and Journal of Pediatric Epilepsy. Dr Baca receives support from grant NINDS-R37-NS31146. Dr Vickrey receives support from grant NINDS R37 NS31146. She serves on scientific advisory boards for the Sports Concussion Institute, American Heart Association, and the National Institutes of Health. She also serves on the editorial boards of Neurorehabilitation and Neural Repair and Circulation: Cardiovascular Quality and Outcomes, and is a section editor for Stroke; receives research support from the National Institutes of Health (NIA, NINDS), the US Veterans Administration Health Services Research and Development Service, the American Heart Association; and is a consultant to EMD Serono Canada and to Imperial Clinical Research Services, Inc. NR 25 TC 6 Z9 6 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD JUL PY 2013 VL 55 IS 7 BP 661 EP 667 DI 10.1111/dmcn.12143 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 160HO UT WOS:000320109900018 PM 23534842 ER PT J AU Weir, GC AF Weir, G. C. TI Islet encapsulation: advances and obstacles SO DIABETOLOGIA LA English DT Editorial Material DE Beta cell; Biomaterials; Diabetes; Encapsulation; Insulin secretion; Islets ID PORCINE ISLETS; TYPE-1; ALLOGRAFTS AB It has been known for decades that encapsulation can protect transplanted islets from immune destruction in rodents, but it has proved difficult to extend this success to large animals and humans. A new study in this issue by Jacobs-Tulleneers-Thevissen et al (doi: 10.1007/s00125-013-2906-0) advances the field by showing that human islets contained in alginate capsules can function very well, not only in the peritoneal cavity of mice, but also in a human with type 1 diabetes. Many obstacles must still be overcome, but this technology has the potential to safely protect transplanted beta cells from autoimmunity and allorejection. C1 [Weir, G. C.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. [Weir, G. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu NR 18 TC 22 Z9 22 U1 2 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 2013 VL 56 IS 7 BP 1458 EP 1461 DI 10.1007/s00125-013-2921-1 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157FL UT WOS:000319881300002 PM 23636639 ER PT J AU Irgens, HU Molnes, J Johansson, BB Ringdal, M Skrivarhaug, T Undlien, DE Sovik, O Joner, G Molven, A Njolstad, PR AF Irgens, H. U. Molnes, J. Johansson, B. B. Ringdal, M. Skrivarhaug, T. Undlien, D. E. Sovik, O. Joner, G. Molven, A. Njolstad, P. R. TI Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry SO DIABETOLOGIA LA English DT Article DE Genetic screening; MODY; Monogenic diabetes; Permanent neonatal diabetes mellitus; Prevalence ID SULFONYLUREA THERAPY; ACTIVATING MUTATIONS; MOLECULAR-GENETICS; YOUNG MODY; DIAGNOSIS; INSULIN; MELLITUS; KIR6.2; MAJORITY; CHILDREN AB Monogenic diabetes (MD) might be misdiagnosed as type 1 diabetes. The prevalence of MD among children with apparent type 1 diabetes has not been established. Our aim was to estimate the prevalence of common forms of MD in childhood diabetes. We investigated 2,756 children aged 0-14 years with newly diagnosed diabetes who had been recruited to the nationwide population-based Norwegian Childhood Diabetes Registry (NCDR), from July 2002 to March 2012. Completeness of ascertainment was 91%. Children diagnosed with diabetes who were under12 months of age were screened for mutations in KCNJ11, ABCC8 and INS. Children without GAD and protein tyrosine phosphatase-like protein antibodies were screened in two ways. Those who had a parent with diabetes were screened for mutations in HNF1A, HNF4A, INS and MT-TL1. Children with HbA(1c) < 7.5% (< 58 mmol/mol) and no insulin requirement were screened for mutations in GCK. Finally, we searched the Norwegian MODY Registry for children with genetically verified MD. We identified 15 children harbouring a mutation in HNF1A, nine with one in GCK, four with one in KCNJ11, one child with a mutation in INS and none with a mutation in MT-TL1. The minimum prevalence of MD in the NCDR was therefore 1.1%. By searching the Norwegian MODY Registry, we found 24 children with glucokinase-MODY, 15 of whom were not present in the NCDR. We estimated the minimum prevalence of MD among Norwegian children to be 3.1/100,000. This is the first prevalence study of the common forms of MD in a nationwide, population-based registry of childhood diabetes. We found that 1.1% of patients in the Norwegian Childhood Diabetes Registry had MD. C1 [Irgens, H. U.; Molnes, J.; Johansson, B. B.; Ringdal, M.; Sovik, O.; Molven, A.; Njolstad, P. R.] Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway. [Irgens, H. U.; Molnes, J.; Johansson, B. B.; Ringdal, M.; Njolstad, P. R.] Haukeland Hosp, Dept Paediat, N-5021 Bergen, Norway. [Molnes, J.; Johansson, B. B.; Ringdal, M.] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Skrivarhaug, T.; Joner, G.] Oslo Univ Hosp, Dept Paediat, Oslo, Norway. [Undlien, D. E.] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Undlien, D. E.] Univ Oslo, Oslo, Norway. [Joner, G.] Univ Oslo, Inst Hlth & Soc, Oslo, Norway. [Molven, A.] Univ Bergen, Gade Inst, Bergen, Norway. [Molven, A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Njolstad, P. R.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Njolstad, PR (reprint author), Broad Inst Harvard & MIT, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM pal.njolstad@uib.no OI Johansson, Bente Berg/0000-0001-8893-1915 FU Western Norway Regional Authority; University of Bergen; Haukeland University Hospital; Innovest; Norwegian Research Council; European Research Council; KG Jebsen Foundation FX Funding was received from Western Norway Regional Authority (H. Irgens, P. R. Njolstad), University of Bergen (A. Molven, P. R. Njolstad), Haukeland University Hospital (H. Irgens, P. R. Njolstad), Innovest (P. R. Njolstad), the Norwegian Research Council (P. R. Njolstad), the European Research Council (P. R. Njolstad), and the KG Jebsen Foundation (P. R. Njolstad.). NR 34 TC 21 Z9 23 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 2013 VL 56 IS 7 BP 1512 EP 1519 DI 10.1007/s00125-013-2916-y PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157FL UT WOS:000319881300008 PM 23624530 ER PT J AU Abdo, S Lo, CS Chenier, I Shamsuyarova, A Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Abdo, S. Lo, C. -S. Chenier, I. Shamsuyarova, A. Filep, J. G. Ingelfinger, J. R. Zhang, S. -L. Chan, J. S. D. TI Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice SO DIABETOLOGIA LA English DT Article DE Akita mice; Angiotensin-converting enzyme 2; Angiotensinogen; Diabetes; Heterogeneous nuclear ribonucleoprotein F; Heterogeneous nuclear ribonucleoprotein K; Hypertension; Insulin; Kidney injury ID PROXIMAL TUBULAR CELLS; BINDING PROTEIN; URINARY ANGIOTENSINOGEN; TRANSGENIC MICE; HIGH GLUCOSE; RESPONSIVE ELEMENT; BLOOD-PRESSURE; SYSTEM; MOUSE; RNA AB We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita mouse model of type 1 diabetes. Adult male Akita mice (12 weeks old) were treated with insulin implants and killed at week 16. Untreated non-Akita littermates served as controls. The effects of insulin on blood glucose, systolic BP (SBP), renal proximal tubular cell (RPTC) gene expression and interstitial fibrosis were studied. We also examined immortalised rat RPTCs stably transfected with control plasmid or with plasmid containing rat Agt promoter in vitro. Insulin treatment normalised blood glucose levels and SBP, inhibited renal AGT expression but enhanced hnRNP F, hnRNP K and angiotensin-converting enzyme-2 expression, attenuated renal hypertrophy and glomerular hyperfiltration and decreased urinary albumin/creatinine ratio, as well as AGT and angiotensin II levels, in Akita mice. In vitro, insulin inhibited Agt but stimulated Hnrnpf and Hnrnpk expression in high-glucose media via p44/42 mitogen-activated protein kinase signalling in RPTCs. Transfection with Hnrnpf or Hnrnpk small interfering RNAs prevented insulin inhibition of Agt expression in RPTCs. These data indicate that insulin prevents hypertension and attenuates kidney injury, at least in part, through suppressing renal Agt transcription via upregulation of hnRNP F and hnRNP K expression in diabetic Akita mice. HnRNP F and hnRNP K may be potential targets in the treatment of hypertension and kidney injury in diabetes. C1 [Abdo, S.; Lo, C. -S.; Chenier, I.; Shamsuyarova, A.; Zhang, S. -L.; Chan, J. S. D.] Univ Montreal, CHUM, Hotel Dieu Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada. [Filep, J. G.] Univ Montreal, Hop Maisonneuve Rosemont, Ctr Rech, Montreal, PQ H2W 1T8, Canada. [Ingelfinger, J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, CHUM, Hotel Dieu Hosp, Ctr Rech, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU Canadian Institutes of Health Research (CIHR) [MOP-93650, MOP-84363, MOP-16088, MOP-86450, MOP-64283]; Heart and Stroke Foundation of Quebec (HSFQ); National Institutes of Health [HL-48455] FX The study was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP-93650, MOP-84363 and MOP-16088 to J. S. D. Chan; MOP-86450 to S.-L. Zhang; and MOP-64283 to J. G. Filep), the Heart and Stroke Foundation of Quebec (HSFQ to J. S. D. Chan), and the National Institutes of Health (HL-48455 to J. R. Ingelfinger). Editorial assistance was provided by the CRCHUM Research Support Office. NR 49 TC 3 Z9 3 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 2013 VL 56 IS 7 BP 1649 EP 1660 DI 10.1007/s00125-013-2910-4 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157FL UT WOS:000319881300023 PM 23609310 ER PT J AU Larson, JL Huttenhower, C Quackenbush, J Yuan, GC AF Larson, Jessica L. Huttenhower, Curtis Quackenbush, John Yuan, Guo-Cheng TI A tiered hidden Markov model characterizes multi-scale chromatin states SO GENOMICS LA English DT Article DE Hidden Markov model; Chromatin; Computational biology ID EMBRYONIC STEM-CELLS; HUMAN GENOME; GENE-EXPRESSION; NONCODING RNAS; EPIGENETIC DOMAINS; PLURIPOTENT; REVEALS; SEGMENTATION; TRANSCRIPTS; PSEUDOGENES AB Precise characterization of chromatin states is an important but difficult task for understanding the regulatory role of chromatin. A number of computational methods have been developed with varying levels of success. However, a remaining challenge is to model epigenomic patterns over multi-scales, as each histone mark is distributed with its own characteristic length scale. We developed a tiered hidden Markov model and applied it to analyze a ChIP-seq dataset in human embryonic stem cells. We identified a two-tier structure containing 15 distinct bin-level chromatin states grouped into three domain-level states. Whereas the bin-level states capture the local variation of histone marks, the domain-level states detect large-scale variations. Compared to bin-level states, the domain-level states are more robust and coherent. We also found active regions in intergenic regions that upon closer examination were expressed non-coding RNAs and pseudogenes. These results provide insights into an additional layer of complexity in chromatin organization. (C) 2013 Elsevier Inc. All rights reserved. C1 [Larson, Jessica L.; Huttenhower, Curtis; Quackenbush, John; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Quackenbush, John; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Yuan, GC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM larsonj5@gene.com; chuttenh@hsph.harvard.edu; johng@jimmy.harvard.edu; gcyuan@jimmy.harvard.edu OI Huttenhower, Curtis/0000-0002-1110-0096 FU NIH [HG006778, 1P01HL105339]; NSF [DBI-1053486] FX We are grateful to Drs. Manolis.Kellis, Jason Ernst, Mark Gerstein, and Pradipta Ray for helpful discussions. This research was supported by the NIH grant HG006778 to GY the NSF grant DBI-1053486 to CH, and the NIH grant 1P01HL105339 to JQ. NR 46 TC 2 Z9 2 U1 0 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2013 VL 102 IS 1 BP 1 EP 7 DI 10.1016/j.ygeno.2013.03.009 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 164NA UT WOS:000320415600001 PM 23570996 ER PT J AU Kelly, AD Hill, KE Correll, M Hu, L Wang, YE Rubio, R Duan, SH Quackenbush, J Spentzos, D AF Kelly, Andrew D. Hill, Katherine E. Correll, Mick Hu, Lan Wang, Yaoyu E. Rubio, Renee Duan, Shenghua Quackenbush, John Spentzos, Dimitrios TI Next-generation sequencing and microarray-based interrogation of microRNAs from formalin-fixed, paraffin-embedded tissue: Preliminary assessment of cross-platform concordance SO GENOMICS LA English DT Article DE RNA-sequencing; Microarrays; Paraffin-tissue ID GENE-EXPRESSION; RNA-SEQ; ARRAY; CANCER AB Next-generation sequencing is increasingly employed in biomedical investigations. Strong concordance between microarray and mRNA-seq levels has been reported in high quality specimens but information is lacking on formalin-fixed, paraffin-embedded (FFPE) tissues, and particularly for microRNA (miRNA) analysis. We conducted a preliminary examination of the concordance between miRNA-seq and cDNA-mediated annealing, selection, extension, and ligation (DASL) miRNA assays. Quantitative agreement between platforms is moderate (Spearman correlation 0.514-0.596) and there is discordance of detection calls on a subset of miRNAs. Quantitative PCR (q-RT-PCR) performed for several discordant miRNAs confirmed the presence of most sequences detected by miRNA-seq but not by DASL but also that miRNA-seq did not detect some sequences, which DASL confidently detected. Our results suggest that miRNA-seq is specific, with few false positive calls, but it may not detect certain abundant miRNAs in FFPE tissue. Further work is necessary to fully address these issues that are pertinent for translational research. (C) 2013 Published by Elsevier Inc. C1 [Kelly, Andrew D.; Hill, Katherine E.; Spentzos, Dimitrios] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Sarcoma Program,Dept Med, Boston, MA 02215 USA. [Correll, Mick; Hu, Lan; Wang, Yaoyu E.; Rubio, Renee; Duan, Shenghua; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Spentzos, D (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Sarcoma Program,Dept Med, Boston, MA 02215 USA. EM andrew.kelly2010@gmail.com; khill5@bidmc.harvard.edu; mcorrell@jimmy.harvard.edu; lanhu@jimmy.harvard.edu; yewang@jimmy.harvard.edu; rrubio@jimmy.harvard.edu; duan@jimmy.harvard.edu; johnq@jimmy.harvard.edu; dspentzo@bidmc.harvard.edu OI Kelly, Andrew/0000-0002-5338-7689 FU The National Institutes of Health [K22 CA138716-01A2, U19 CA148065]; Dana-Farber Cancer Institute Strategic Plan Fund; Beth Israel Deaconess Medical Center FX The authors would like to thank the following institutions for the funding provided for this study:; The National Institutes of Health [K22 CA138716-01A2 to D.S., U19 CA148065 to J.Q.]; the Dana-Farber Cancer Institute Strategic Plan Fund [to M.C., J.Q]; and a donation by Dr Richard and Virginia Clemmer to the sarcoma program at Beth Israel Deaconess Medical Center [to D.S.]. The authors also wish to thank Antonio R. Perez-Atayde and Kyle Kurek (Boston Children's Hospital, Department of Pathology) and Jeffrey Goldsmith (BIDMC Department of Pathology) for providing FFPE sample for this study. NR 19 TC 12 Z9 12 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2013 VL 102 IS 1 BP 8 EP 14 DI 10.1016/j.ygeno.2013.03.008 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 164NA UT WOS:000320415600002 PM 23562991 ER PT J AU Kanda, M Knight, S Topazian, M Syngal, S Farrell, J Lee, J Kamel, I Lennon, AM Borges, M Young, A Fujiwara, S Seike, J Eshleman, J Hruban, RH Canto, MI Goggins, M AF Kanda, Mitsuro Knight, Spencer Topazian, Mark Syngal, Sapna Farrell, James Lee, Jeffrey Kamel, Ihab Lennon, Anne Marie Borges, Michael Young, Angela Fujiwara, Sho Seike, Junro Eshleman, James Hruban, Ralph H. Canto, Marcia Irene Goggins, Michael TI Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts SO GUT LA English DT Article ID PAPILLARY MUCINOUS NEOPLASMS; HIGH-RISK INDIVIDUALS; K-RAS MUTATIONS; INTRAEPITHELIAL NEOPLASIA; ENDOSCOPIC ULTRASONOGRAPHY; TELOMERASE ACTIVITY; EARLY-DIAGNOSIS; FAMILY-HISTORY; CANCER; SAMPLES AB Objective Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this study we evaluated the utility of detecting mutant DNA in secretin-stimulated pancreatic juice. Design Secretin-stimulated pancreatic juice was collected from the duodenum of 291 subjects enrolled in Cancer of the Pancreas Screening trials at five US academic medical centres. The study population included subjects with a familial predisposition to pancreatic cancer who underwent pancreatic screening, and disease controls with normal pancreata, chronic pancreatitis, sporadic intraductal papillary mucinous neoplasm (IPMN) or other neoplasms. Somatic GNAS mutations (reported prevalence similar to 66% of IPMNs) were measured using digital high-resolution melt-curve analysis and pyrosequencing. Results GNAS mutations were detected in secretin-stimulated pancreatic juice samples of 50 of 78 familial and sporadic cases of IPMN(s) (64.1%), 15 of 33 (45.5%) with only diminutive cysts (<5 mm), but none of 57 disease controls. GNAS mutations were also detected in five of 123 screened subjects without a pancreatic cyst. Among 97 subjects who had serial pancreatic evaluations, GNAS mutations detected in baseline juice samples predicted subsequent emergence or increasing size of pancreatic cysts. Conclusion Duodenal collections of secretin-stimulated pancreatic juice from patients with IPMNs have a similar prevalence of mutant GNAS to primary IPMNs, indicating that these samples are an excellent source of mutant DNA from the pancreas. The detection of GNAS mutations before an IPMN is visible suggests that analysis of pancreatic juice has the potential to help in the risk stratification and surveillance of patients undergoing pancreatic screening. C1 [Kanda, Mitsuro; Knight, Spencer; Borges, Michael; Young, Angela; Fujiwara, Sho; Seike, Junro; Eshleman, James; Hruban, Ralph H.; Canto, Marcia Irene; Goggins, Michael] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA. [Topazian, Mark] Mayo Clin, Baltimore, MD USA. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Farrell, James] Univ Calif Los Angeles, Los Angeles, CA USA. [Lee, Jeffrey] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kamel, Ihab] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Radiol, Baltimore, MD 21205 USA. [Lennon, Anne Marie; Canto, Marcia Irene; Goggins, Michael] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Med, Baltimore, MD 21205 USA. [Eshleman, James; Hruban, Ralph H.; Goggins, Michael] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Oncol, Baltimore, MD 21205 USA. RP Goggins, M (reprint author), Johns Hopkins Med Inst, Dept Pathol, 1550 Orleans St, Baltimore, MD 21231 USA. EM mgoggins@jhmi.edu RI Kanda, Mitsuro/M-4891-2014 FU NIH [CA62924, R01CA120432, C2CA148376]; Lustgarten Foundation for Pancreatic Cancer Research; Jimmy V Foundation; Michael Rolfe Foundation; Karp Family H H Metals, Inc Fund for Cancer Research Michael Hooven and Susan Spies FX This work was supported by NIH grants (CA62924, R01CA120432, and RC2CA148376), the Lustgarten Foundation for Pancreatic Cancer Research, the Jimmy V Foundation, the Michael Rolfe Foundation, and Karp Family H H Metals, Inc Fund for Cancer Research Michael Hooven and Susan Spies. Material support: ChiRhoClin (secretin). NR 46 TC 61 Z9 62 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUL PY 2013 VL 62 IS 7 BP 1024 EP 1033 DI 10.1136/gutjnl-2012-302823 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 158MO UT WOS:000319975900012 PM 22859495 ER PT J AU Peraino, JS Zhang, HP Li, GY Huang, CA Wang, ZR AF Peraino, Jaclyn Stromp Zhang, Huiping Li, Guoying Huang, Christene A. Wang, Zhirui TI Molecular basis of cross-species reactivities of human versus porcine CTLA-4 SO HUMAN IMMUNOLOGY LA English DT Article ID EXPRESSION; CD28; B7-1 AB The binding motif of human CTLA-4 is well known to be MYPPPY and for porcine CTLA-4 the binding motif is LYPPPY. Is this single amino acid difference of methionine (M) versus leucine (L) critical for the CTLA-4 binding? Recently, we have reported that the recombinant soluble porcine CTLA-4 was incapable of binding to human CD80. In this study we mutated L to M in the binding motif of the soluble porcine CTLA-4 and mutated M to L in the binding motif of the soluble human CTLA-4. We then analyzed how these mutations affected the binding affinity of the mutants to both porcine and human CD80(+) cells. The soluble porcine CTLA-4-L97M mutant partially lost its binding affinity to porcine CD80 compared to the wild-type and conferred very weak binding ability to human CD80. These results indicate that the L in the binding motif of porcine CTLA-4 is important for determining its binding ability to porcine CD80. Wild-type soluble human CTLA-4 binds to both human and porcine CD80 with comparable affinity, however, the soluble human CTLA-4-M97L mutant almost lost its binding ability to human CD80 and increased its binding ability to porcine CD80. These results indicate that M in the human CTLA-4 binding motif is extremely critical for its binding to human CD80. Those data suggest that the human CTLA-4 based recombinant protein drugs such as human CTLA-4-Ig can be used and/or tested in a porcine model. Conversely, the use of porcine CTLA-4 based recombinant protein drugs such as porcine CTLA-4-Ig is restricted to swine models. The difference in binding specificity of CTLA-4 observed in this study may be useful for studies such as pig to nonhuman primate xeno-transplantation. Porcine CTLA-4- and human CTLA-4-M97L mutant-based recombinant protein drugs can be used to specifically block the direct presentation by donor antigen presenting cells in pig to nonhuman primate xeno-transplantation. Human CTLA-4-M97L mutant-based recombinant protein drugs will be more ideal as it is without immunogenicity to human being. (c) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. C1 [Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02129 USA. DF HCC MGH Recombinant Prot Express & Purificat C, Boston, MA USA. RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149-6113,13th St, Boston, MA 02129 USA. EM zhirui.wang@tbrc.mgh.harvard.edu FU Dana Farber/Harvard Cancer Center Core development grant FX The work was supported in part by Dana Farber/Harvard Cancer Center Core development grant. We acknowledge the support, guidance and intensive manuscript review of Dr. David H. Sachs, Scientific Director of MGH-DF/HCC Recombinant Protein Expression and Purification Core. We thank Dr. Isabel Hanekamp and Sharon Germana for manuscript review. NR 10 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JUL PY 2013 VL 74 IS 7 BP 842 EP 848 DI 10.1016/j.humimm.2013.04.002 PG 7 WC Immunology SC Immunology GA 157KW UT WOS:000319896000005 PM 23602875 ER PT J AU Zhou, WC Zhang, F Chen, XL Shen, YP Lupski, JR Jin, L AF Zhou, Weichen Zhang, Feng Chen, Xiaoli Shen, Yiping Lupski, James R. Jin, Li TI Increased genome instability in human DNA segments with self-chains: homology-induced structural variations via replicative mechanisms SO HUMAN MOLECULAR GENETICS LA English DT Article ID COPY NUMBER VARIATION; INVERTED REPEATS; REARRANGEMENTS; SEQUENCE; CANCER; DISORDERS; REVEALS; DISEASE; RECOMBINATION; DUPLICATIONS AB Environmental factors including ionizing radiation and chemical agents have been known to be able to induce DNA rearrangements and cause genomic structural variations (SVs); however, the roles of intrinsic characteristics of the human genome, such as regional genome architecture, in SV formation and the potential mechanisms underlying genomic instability remain to be further elucidated. Recently, locus-specific observations showed that self-chain (SC), a group of short low-copy repeats (LCRs) in the human genome, can induce autism-associated SV mutations of the MECP2 and NRXN1 genes. In this study, we conducted a genome-wide analysis to investigate SCs and their potential roles in genomic SV formation. Utilizing a vast amount of human SV data, we observed a significant biased distribution of human germline SV breakpoints to SC regions. Notably, the breakpoint distribution pattern is different between SV types across deletion, duplication, inversion and insertion. Our observations were coincident with a mechanism of SC-induced DNA replicative errors, whereas SC may sporadically be used as substrates of nonallelic homologous recombination (NAHR). This contention was further supported by our consistent findings in somatic SV mutations of cancer genomes, suggesting a general mechanism of SC-induced genome instability in human germ and somatic cells. C1 [Zhou, Weichen; Zhang, Feng; Jin, Li] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Zhou, Weichen; Zhang, Feng; Jin, Li] Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. [Chen, Xiaoli; Shen, Yiping] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Chen, Xiaoli] Capital Inst Pediat, Beijing Municipal Key Lab Child Dev & Nutri, Beijing 100020, Peoples R China. [Shen, Yiping] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Shen, Yiping] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Zhang, F (reprint author), Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. EM zhangfeng@fudan.edu.cn RI Zhang, Feng/C-7735-2009; Jin, Li/C-1468-2009; OI Jin, Li/0000-0002-4546-2415; Zhou, Weichen/0000-0003-4755-1072 FU National Basic Research Program of China [2012CB944600, 2011CBA00401]; National S&T Major Special Project [2011ZX09102-010-01]; National Natural Science Foundation of China [81222014, 31171210, 31000552]; Shanghai Pujiang Program [10PJ1400300]; Shu Guang Project [12SG08]; National Institute of Neurological Disorders and Stroke, NIH [R01NS058529] FX This work was supported by National Basic Research Program of China (2012CB944600 and 2011CBA00401), National S&T Major Special Project (2011ZX09102-010-01), National Natural Science Foundation of China (81222014, 31171210 and 31000552), Shanghai Pujiang Program (10PJ1400300), Shu Guang Project (12SG08), and National Institute of Neurological Disorders and Stroke, NIH (R01NS058529). NR 48 TC 10 Z9 11 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2013 VL 22 IS 13 BP 2642 EP 2651 DI 10.1093/hmg/ddt113 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 160MZ UT WOS:000320125100009 PM 23474816 ER PT J AU Cousminer, DL Berry, DJ Timpson, NJ Ang, W Thiering, E Byrne, EM Taal, HR Huikari, V Bradfield, JP Kerkhof, M Groen-Blokhuis, MM Kreiner-Moller, E Marinelli, M Holst, C Leinonen, JT Perry, JRB Surakka, I Pietilainen, O Kettunen, J Anttila, V Kaakinen, M Sovio, U Pouta, A Das, S Lagou, V Power, C Prokopenko, I Evans, DM Kemp, JP St Pourcain, B Ring, S Palotie, A Kajantie, E Osmond, C Lehtimaki, T Viikari, JS Kahonen, M Warrington, NM Lye, SJ Palmer, LJ Tiesler, CMT Flexeder, C Montgomery, GW Medland, SE Hofman, A Hakonarson, H Guxens, M Bartels, M Salomaa, V Murabito, JM Kaprio, J Sorensen, TIA Ballester, F Bisgaard, H Boomsma, DI Koppelman, GH Grant, SFA Jaddoe, VWV Martin, NG Heinrich, J Pennell, CE Raitakari, OT Eriksson, JG Smith, GD Hypponen, E Jarvelin, MR McCarthy, MI Ripatti, S Widen, E AF Cousminer, Diana L. Berry, Diane J. Timpson, Nicholas J. Ang, Wei Thiering, Elisabeth Byrne, Enda M. Taal, H. Rob Huikari, Ville Bradfield, Jonathan P. Kerkhof, Marjan Groen-Blokhuis, Maria M. Kreiner-Moller, Eskil Marinelli, Marcella Holst, Claus Leinonen, Jaakko T. Perry, John R. B. Surakka, Ida Pietilainen, Olli Kettunen, Johannes Anttila, Verneri Kaakinen, Marika Sovio, Ulla Pouta, Anneli Das, Shikta Lagou, Vasiliki Power, Chris Prokopenko, Inga Evans, David M. Kemp, John P. St Pourcain, Beate Ring, Susan Palotie, Aarno Kajantie, Eero Osmond, Clive Lehtimaki, Terho Viikari, Jorma S. Kahonen, Mika Warrington, Nicole M. Lye, Stephen J. Palmer, Lyle J. Tiesler, Carla M. T. Flexeder, Claudia Montgomery, Grant W. Medland, Sarah E. Hofman, Albert Hakonarson, Hakon Guxens, Monica Bartels, Meike Salomaa, Veikko Murabito, Joanne M. Kaprio, Jaakko Sorensen, Thorkild I. A. Ballester, Ferran Bisgaard, Hans Boomsma, Dorret I. Koppelman, Gerard H. Grant, Struan F. A. Jaddoe, Vincent W. V. Martin, Nicholas G. Heinrich, Joachim Pennell, Craig E. Raitakari, Olli T. Eriksson, Johan G. Smith, George Davey Hypponen, Elina Jarvelin, Marjo-Riitta McCarthy, Mark I. Ripatti, Samuli Widen, Elisabeth CA ReproGen Consortium Early Growth Genetics EGG TI Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity SO HUMAN MOLECULAR GENETICS LA English DT Article ID CHROMOSOME 16P11.2; POPULATION COHORT; FACTOR RECEPTOR-3; AGE; MENARCHE; MUTATIONS; VARIANTS; OBESITY; BIRTH; ACHONDROPLASIA AB The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P 1.67 10(8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits. C1 [Cousminer, Diana L.; Leinonen, Jaakko T.; Surakka, Ida; Pietilainen, Olli; Kettunen, Johannes; Anttila, Verneri; Palotie, Aarno; Kaprio, Jaakko; Ripatti, Samuli; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland. [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland. [Berry, Diane J.; Power, Chris; Hypponen, Elina] UCL Inst Child Hlth, MRC, Ctr Paediat Epidemiol & Biostat, Ctr Epidemiol Child Hlth, London, England. [Timpson, Nicholas J.; Evans, David M.; Kemp, John P.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, MRC, Ctr Causal Analyses Translat Epidemiol, Bristol, Avon, England. [Kemp, John P.; St Pourcain, Beate; Ring, Susan] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Ang, Wei; Warrington, Nicole M.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia. [Thiering, Elisabeth; Tiesler, Carla M. T.; Flexeder, Claudia; Heinrich, Joachim] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Byrne, Enda M.; Montgomery, Grant W.; Medland, Sarah E.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Taal, H. Rob; Hofman, Albert; Jaddoe, Vincent W. V.] Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands. [Taal, H. Rob; Hofman, Albert; Jaddoe, Vincent W. V.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Taal, H. Rob; Jaddoe, Vincent W. V.] Erasmus MC, Dept Pediat, Rotterdam, Netherlands. [Huikari, Ville; Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, FI-90014 Oulu, Finland. [Kaakinen, Marika; Pouta, Anneli; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, FI-90014 Oulu, Finland. [Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F. A.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Hakonarson, Hakon; Grant, Struan F. A.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Kerkhof, Marjan] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Koppelman, Gerard H.] Univ Groningen,Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergol, GRIAC Res Inst, Groningen, Netherlands. [Groen-Blokhuis, Maria M.; Bartels, Meike; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Kreiner-Moller, Eskil; Bisgaard, Hans] Univ Copenhagen, Copenhagen Univ Hosp, Copenhagen Prospect Studies Asthma Childhood, Gentofte, Denmark. [Marinelli, Marcella; Guxens, Monica] Ctr Res Environm Epidemiol CREAL, Barcelona, Catalonia, Spain. [Marinelli, Marcella; Guxens, Monica] Hosp del Mar Res Inst IMIM, Barcelona, Catalonia, Spain. [Marinelli, Marcella; Guxens, Monica; Ballester, Ferran] CIBERESP, Barcelona, Catalonia, Spain. [Holst, Claus; Sorensen, Thorkild I. A.] Copenhagen Univ Hosp, Inst Prevent Med, Copenhagen, Denmark. [Perry, John R. B.; Sorensen, Thorkild I. A.] Univ Exeter, Exeter Med Sch, Exeter, Devon, England. [Perry, John R. B.; Lagou, Vasiliki; Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Lagou, Vasiliki; Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England. [Perry, John R. B.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Surakka, Ida; Kettunen, Johannes; Kajantie, Eero; Salomaa, Veikko; Eriksson, Johan G.; Ripatti, Samuli] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Helsinki, Finland. [Pietilainen, Olli; Anttila, Verneri; Palotie, Aarno; Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge, England. [Sovio, Ulla; Das, Shikta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, London, England. [Sovio, Ulla] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England. [Anttila, Verneri; Palotie, Aarno] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Osmond, Clive] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Lehtimaki, Terho] Univ Hosp, Fimlab Labs, Dept Clin Chem, Turku, Finland. [Lehtimaki, Terho] Univ Tampere, FIN-33101 Tampere, Finland. [Viikari, Jorma S.] Univ Turku, Dept Med, SF-20500 Turku, Finland. [Kahonen, Mika; Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Kahonen, Mika; Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland. [Lye, Stephen J.; Palmer, Lyle J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Tiesler, Carla M. T.] Univ Munich, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutr Med, Munich, Germany. [Hakonarson, Hakon; Grant, Struan F. A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Sorensen, Thorkild I. A.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Ballester, Ferran] Ctr Publ Hlth Res CSISP, Div Environm & Hlth, Valencia, Spain. [Ballester, Ferran] Univ Valencia, Sch Nursing, Valencia, Spain. [Eriksson, Johan G.] Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Kajantie, Eero] Helsinki Univ Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Kajantie, Eero] Univ Helsinki, Helsinki, Finland. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Anttila, Verneri] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri] Harvard Univ, Sch Med, Boston, MA USA. [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, FI-90220 Oulu 90029, Oys, Finland. [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children & Young People & Families, FI-90101 Oulu, Finland. RP Widen, E (reprint author), Univ Helsinki, Inst Mol Med Finland FIMM, Tukholmankatu 8,POB 20, FIN-00014 Helsinki, Finland. EM elisabeth.widen@helsinki.fi RI Medland, Sarah/C-7630-2013; Visser, Jenny /F-8156-2011; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Prokopenko, Inga/H-3241-2014; Rudan, Igor/I-1467-2012; Price, Thomas/B-7372-2008; Fox, Laura /C-6249-2016; Bisgaard, Hans/N-4761-2016; Davey Smith, George/A-7407-2013; Kolcic, Ivana/E-2713-2017; Palmer, Lyle/K-3196-2014; Warrington, Nicole/P-4868-2014; Evans, David/H-6325-2013; Ness, Andy/M-7612-2013; Lagou, Vasiliki/N-8451-2013; Hypponen, Elina/B-2596-2014; Gasparini, Paolo/B-6173-2014; Lye, Stephen/E-7269-2013; Bartels, Meike/D-4492-2014; d'Adamo, Adamo Pio/G-4064-2011; Aspelund, Thor/C-5983-2008; Deloukas, Panos/B-2922-2013; Byrne, Enda/J-6068-2014; Smith, Albert Vernon/K-5150-2015; OI Medland, Sarah/0000-0003-1382-380X; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139; Prokopenko, Inga/0000-0003-1624-7457; Rudan, Igor/0000-0001-6993-6884; Price, Thomas/0000-0001-7356-2109; Bisgaard, Hans/0000-0003-4131-7592; Davey Smith, George/0000-0002-1407-8314; Kolcic, Ivana/0000-0001-7918-6052; Eriksson, Johan/0000-0002-2516-2060; Kemp, John/0000-0002-9105-2249; Evans, David/0000-0003-0663-4621; Kaprio, Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie A/0000-0002-6793-2262; Hattersley, Andrew/0000-0001-5620-473X; de Geus, Eco/0000-0001-6022-2666; Palmer, Lyle/0000-0002-1628-3055; Warrington, Nicole/0000-0003-4195-775X; Ness, Andy/0000-0003-3548-9523; Hypponen, Elina/0000-0003-3670-9399; Bartels, Meike/0000-0002-9667-7555; d'Adamo, Adamo Pio/0000-0001-9367-4909; Aspelund, Thor/0000-0002-7998-5433; Deloukas, Panos/0000-0001-9251-070X; Murabito, Joanne/0000-0002-0192-7516; Thiering, Elisabeth/0000-0002-5429-9584; Kaakinen, Marika/0000-0002-9228-0462; Anttila, Verneri/0000-0002-0073-4675; MARONGIU, MARA/0000-0002-7321-2384; Byrne, Enda/0000-0002-9491-7797; Gudbjartsson, Daniel/0000-0002-5222-9857; Esko, Tonu/0000-0003-1982-6569; Smith, Albert Vernon/0000-0003-1942-5845; Zgaga, Lina/0000-0003-4089-9703; Tryggvadottir, Laufey/0000-0001-8067-9030; Lakka, Timo/0000-0002-9199-2871; Estivill, Xavier/0000-0002-0723-2256; Scherag, Andre/0000-0002-9406-4704; Zeggini, Eleftheria/0000-0003-4238-659X; St Pourcain, Beate/0000-0002-4680-3517; Kreiner, Eskil/0000-0003-1204-2438; Karasik, David/0000-0002-8826-0530; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Navarro, Pau/0000-0001-5576-8584; Martin, Nicholas/0000-0003-4069-8020 FU Academy of Finland [120315, 134839, 129297, 218029, 209072, 129255, 126925, 121584, 124282, 129378, 117787, 41071, 100499, 205585, 118555, 104781, 129418, 141054]; Academy of Finland Center of Excellence in Complex Disease Genetics [213506, 129680]; Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]; Australian Research Council [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]; British Heart Foundation; Canadian Institutes of Health Research [MOP-82893]; Conselleria de Sanitat Generalitat Valenciana; Fundacion Roger Torne; Dutch Asthma Fonds; Emil Aaltonen Foundation; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development [21000074, ZonMw 90700303, 916.10159]; European Commission (ENGAGE project) [HEALTH-F4-2007-201413]; European Commission (EURO-BLCS) [QLG1-CT-2000-01643]; European Research Council [ERC-230374]; Finnish Cultural Foundation; Finnish Foundation of Cardiovascular Research; Fundacio La Marato de TV3; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Genomics of Developmental Trajectories in Twins [1RC2MH089 995-01]; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; Infants Research Foundation; Institute Development Award from the Children's Hospital of Philadelphia; Instituto de Salud Carlos III [CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647]; Juho Vainio Foundation; Ludwig-Maximilians-University's innovative research priority project MC-Health; Medical Research Council [G0601653, G0000934, G0500539, G0600705]; National Institutes of Health [R01 HD056465, 5R01MH63706:02]; National Institute for Alcohol Abuse and Alcoholism [AA-12502, AA-09203, AA-08315]; NIH Heart, Lung and Blood Institute [5R01HL087679-02]; NIH Heart, Lung and Blood Institute through the STAMPEED program [1RL1MH083268-01]; National Health and Medical Research Council of Australia [403981, 003209]; Netherlands Organization for Scientific research [NWO/SPI 56-464-14192]; Spanish Ministry of Science and Innovation [SAF2008-00357]; Stichting Astmabestrijding and Ministry of the Environment; Social Insurance Institution of Finland; Telethon Institute for Child Health Research and Women; Twin-family database for behavior genetics and genomics studies [NWO 480-04-004]; Type 1 Diabetes Genetics Consortium [U01 DK062418]; Paavo Nurmi Foundation; Raine Medical Research Foundation; Research Development Award from the Cotswold Foundation; UK Medical Research Council [74882]; University of Bristol; University of Western Australia; University Hospital Oulu; University of Oulu [75617]; UWA Faculty of Medicine, Dentistry and Health Sciences; Wellcome Trust [076467, 068545/Z/02, 084762MA, 092447/Z/10/Z, WT083431MA]; ZonMw: the Netherlands Organisation for Health Research and Development; Helsinki Biomedical Graduate Program; MRC Centre for Causal Analyses in Translational Epidemiology [RD1634]; European Community's Seventh Framework Programme [FP7/2007-2013]; European Community's ENGAGE project [HEALTH-F4-2007-201413]; Tampere and Turku University Hospital Medical Funds [9M048, 9N035]; Tampere Tuberculosis Foundation; National Health and Medical Research Council [613608] FX This work was supported by the Academy of Finland (grant numbers 120315, 134839, 129297, 218029, 209072, 129255, 126925, 121584, 124282, 129378, 117787, 41071, 100499, 205585, 118555, 104781, 120315, 129418, 141054); Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers 213506, 129680); Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); Australian Research Council (grant numbers A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921); British Heart Foundation; Canadian Institutes of Health Research (grant number MOP-82893); Conselleria de Sanitat Generalitat Valenciana, and Fundacion Roger Torne; Dutch Asthma Fonds; Emil Aaltonen Foundation; Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development (grant number 21000074); European Commission (ENGAGE project and grant agreement HEALTH-F4-2007-201413; EURO-BLCS, Framework 5 award QLG1-CT-2000-01643); European Research Council (grant number ERC-230374); Finnish Cultural Foundation; Finnish Foundation of Cardiovascular Research; Fundacio La Marato de TV3, Generalitat de Catalunya (grant number CIRIT 1999SGR 00241); Genomics of Developmental Trajectories in Twins (grant number 1RC2MH089 995-01); German Bundesministerium fuer Forschung und Technology (grant numbers 01 AK 803 A-H, 01 IG 07015 G); Infants Research Foundation; Institute Development Award from the Children's Hospital of Philadelphia; Instituto de Salud Carlos III (grant numbers CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647); Juho Vainio Foundation; Ludwig-Maximilians-University's innovative research priority project MC-Health; Medical Research Council (grant numbers G0601653, G0000934, G0500539, G0600705, G0601653); National Institutes of Health (grant numbers R01 HD056465, 5R01MH63706:02); National Institute for Alcohol Abuse and Alcoholism (grant numbers AA-12502, AA-09203, AA-08315); NIH Heart, Lung and Blood Institute (grant number 5R01HL087679-02) through the STAMPEED program (grant number 1RL1MH083268-01); National Health and Medical Research Council of Australia (grant numbers 403981, 003209); Netherlands Organization for Scientific research (grant number NWO/SPI 56-464-14192); Spanish Ministry of Science and Innovation (grant number SAF2008-00357); Stichting Astmabestrijding and Ministry of the Environment; Social Insurance Institution of Finland; Telethon Institute for Child Health Research and Women; Twin-family database for behavior genetics and genomics studies (grant number NWO 480-04-004); Type 1 Diabetes Genetics Consortium (grant number U01 DK062418); Paavo Nurmi Foundation; Raine Medical Research Foundation; Research Development Award from the Cotswold Foundation; UK Medical Research Council (grant number 74882); University of Bristol; University of Western Australia; University Hospital Oulu; University of Oulu (grant number 75617); UWA Faculty of Medicine, Dentistry and Health Sciences; Wellcome Trust (grant numbers 076467, 068545/Z/02, 084762MA); and ZonMw: the Netherlands Organisation for Health Research and Development. Personal funding was provided by the Helsinki Biomedical Graduate Program to D. L. C.; Netherlands Organization for Health Research and Development (grant numbers ZonMw 90700303, 916.10159) to V.W.V.J.; Dutch Kidney Foundation (grant number C08.2251) to H. R. T.; ; MRC Centre for Causal Analyses in Translational Epidemiology (grant number RD1634) to G. D. S., D. M. E. and N.J.T.; European Community's Seventh Framework Programme (grant number FP7/2007-2013) and ENGAGE project, grant agreement HEALTH-F4-2007-201413 to I. P. and V. L.; Tampere and Turku University Hospital Medical Funds (grant numbers 9M048, 9N035) to T. L.; Tampere Tuberculosis Foundation to T. L.; National Health and Medical Research Council (grant number 613608) to E. M. B. and Fellowship Scheme to G. W. M.; and Wellcome Trust Sir Henry Wellcome Postdoctoral Research Fellow (grant number 092447/Z/10/Z) to J.R.B.P. J.P.K. is funded by a Wellcome Trust 4-year PhD studentship in molecular, genetic, and life course epidemiology (WT083431MA). NR 43 TC 42 Z9 44 U1 1 U2 45 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2013 VL 22 IS 13 BP 2735 EP 2747 DI 10.1093/hmg/ddt104 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 160MZ UT WOS:000320125100016 PM 23449627 ER PT J AU Adeyemo, O Doi, H Reddy, KR Kaplan, DE AF Adeyemo, O. Doi, H. Reddy, K. Rajender Kaplan, D. E. CA SyNCH Trial Investigators TI Impact of oral silymarin on virus- and non-virus-specific T-cell responses in chronic hepatitis C infection SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis C; interferon-gamma; interferon-stimulated gene; lymphocyte; silymarin; T-cell ID ANTIOXIDANT FLAVONOID MIXTURE; INTERFERON THERAPY; GENE-EXPRESSION; LIVER-DISEASE; MILK THISTLE; PHYSIOLOGICAL-RESPONSES; INTRAVENOUS SILIBININ; COMBINATION THERAPY; ANTIVIRAL THERAPY; IMMUNE-RESPONSE AB Silymarin displays anti-inflammatory effects on T lymphocytes in vitro. The immunomodulatory properties of oral silymarin in vivo in humans with chronic hepatitis C have not previously been characterized. We hypothesized that silymarin would suppress T-cell proliferation and pro-inflammatory cytokine production of virus- and non-virus-specific T cells while increasing anti-inflammatory IL-10 production in vivo. Patients from one site of the SyNCH-HCV double-masked, placebo-controlled study of oral silymarin in prior interferon nonresponders with chronic hepatitis C provided blood samples at baseline and treatment week 20. Mononuclear cells were stimulated with recombinant HCV proteins and controls in 3H-thymidine proliferation assays, IFN ELISPOT and IL-10 ELISPOT. The frequency of CD4+CD25hi and CD4+foxp3+ regulatory T cells, serum cytokine levels, serum IP-10 and lymphocyte interferon-stimulated gene expression were also quantified at baseline and week 20. Thirty-two patients were recruited (10; placebo, 11; 420mg three times a day, 11; 700mg three times a day). Serum ALT and HCV RNA titres did not change in any group. HCV-specific CD4+ T-cell proliferation and the frequency of IFN- and IL-10-producing T cells were not significantly changed in silymarin-treated subjects. However, C.albicans-induced T-cell IFN and phytohaemagglutinin-induced T-cell proliferation were suppressed by silymarin therapy. A trend towards augmentation of interferon-induced ISG15 expression was present in the high-dose silymarin group. While no effect on HCV-specific T cells was identified, these data confirm that high-dose oral silymarin exerts modest nonspecific immunomodulatory effects in vivo. The impact of this anti-inflammatory effect on long-term liver health in chronic hepatitis C merits future clinical investigation. C1 [Adeyemo, O.; Doi, H.; Reddy, K. Rajender; Kaplan, D. E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Kaplan, D. E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. RP Adeyemo, O (reprint author), Philadelphia VA Med Ctr, Res Bldg 21,A402A,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU National Institutes of Health (NIH), National Center for Complementary and Alternative Medicine [AT003573, AT003571, AT003566, AT003560, AT003574]; NIDDK; NIH CTSA Division of Research Resources (University of Pennsylvania) [UL1 RR024134]; Research Career Development Award from the Veterans Health Administration (DEK); University of Pennsylvania (DEK); Center for Molecular Studies in Digestive and Liver Disease (NIH/NIDDK) [P30-DK050306] FX This research was supported with cooperative agreements to the SyNCH Study Group from the National Institutes of Health (NIH), National Center for Complementary and Alternative Medicine: AT003573, AT003571, AT003566, AT003560 and AT003574 with co-funding from the NIDDK, and with support from the NIH CTSA Division of Research Resources (University of Pennsylvania UL1 RR024134). In addition, Rottapharmvertical barMadaus (Monza, Italy and Cologne, Germany) provided both the silymarin and placebo for the trial. Other support was received from a Research Career Development Award from the Veterans Health Administration (DEK), academic development funds from the University of Pennsylvania (DEK) and Center for Molecular Studies in Digestive and Liver Disease (NIH/NIDDK P30-DK050306, DEK, KRR). The authors would like to thank Amina Wirjosemito for sample acquisition. The authors would also like to thank the patients who contributed samples. The content of this article does not reflect the views of the VA or of the US Government. NR 38 TC 4 Z9 4 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUL PY 2013 VL 20 IS 7 BP 453 EP 462 DI 10.1111/jvh.12050 PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 157GL UT WOS:000319884000002 PM 23730838 ER PT J AU Brody, AL Mukhin, AG Shulenberger, S Mamoun, MS Kozman, M Phuong, J Neary, M Luu, T Mandelkern, MA AF Brody, Arthur L. Mukhin, Alexey G. Shulenberger, Stephanie Mamoun, Michael S. Kozman, Maggie Phuong, Jonathan Neary, Meaghan Trinh Luu Mandelkern, Mark A. TI Treatment for Tobacco Dependence: Effect on Brain Nicotinic Acetylcholine Receptor Density SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE tobacco dependence; nicotine; nicotinic acetylcholine receptor; bupropion; cognitive-behavioral therapy; positron emission tomography ID PREDICTING SMOKING-CESSATION; SELF-EFFICACY; WITHDRAWAL SYMPTOMS; CLINICAL-TRIALS; QUIT ATTEMPT; ABSTINENCE; RELAPSE; BUPROPION; SMOKERS; LAPSE AB Cigarette smoking leads to upregulation of brain nicotinic acetylcholine receptors (nAChRs), including the common alpha(4)beta(2)* nAChR subtype. Although a substantial percentage of smokers receive treatment for tobacco dependence with counseling and/or medication, the effect of a standard course of these treatments on nAChR upregulation has not yet been reported. In the present study, 48 otherwise healthy smokers underwent positron emission tomography (PET) scanning with the radiotracer 2-FA (for labeling alpha(4)beta(2)* nAChRs) before and after treatment with either cognitive-behavioral therapy, bupropion HCl, or pill placebo. Specific binding volume of distribution (VS/fP), a measure proportional to a4b2* nAChR density, was determined for regions known to have nAChR upregulation with smoking (prefrontal cortex, brainstem, and cerebellum). In the overall study sample, significant decreases in VS/fP were found for the prefrontal cortex, brainstem, and cerebellum of -20 (+/- 35), -25 (+/- 36), and -25 (+/- 31)%, respectively, which represented movement of VS/fP values toward values found in non-smokers (mean 58.2% normalization of receptor levels). Participants who quit smoking had significantly greater reductions in VS/fP across regions than non-quitters, and correlations were found between reductions in cigarettes per day and decreases in VS/fP for brainstem and cerebellum, but there was no between-group effect of treatment type. Thus, smoking reduction and cessation with commonly used treatments (and pill placebo) lead to decreased alpha(4)beta(2)* nAChR densities across brain regions. Study findings could prove useful in the treatment of smokers by providing encouragement with the knowledge that decreased smoking leads to normalization of specific brain receptors. C1 [Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Brody, Arthur L.; Shulenberger, Stephanie; Mamoun, Michael S.; Kozman, Maggie; Phuong, Jonathan; Neary, Meaghan; Trinh Luu; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA. [Mukhin, Alexey G.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [19XT-0135]; Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award) [I01 CX000412]; Pfizer, Inc.; Phillip Morris, Inc. FX This study was supported by the National Institute on Drug Abuse (ALB (R01 DA20872)), the Tobacco-Related Disease Research Program (ALB (19XT-0135)), and the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412 (ALB)). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.; ALB and MAM were previously co-investigators on a grant funded by Pfizer, Inc. that was unrelated to this study. AGM is a co-investigator on a grant from Phillip Morris, Inc. for research unrelated to this study. All the other authors report no biomedical financial disclosures or potential conflicts of interest. NR 71 TC 10 Z9 10 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2013 VL 38 IS 8 BP 1548 EP 1556 DI 10.1038/npp.2013.53 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 163WJ UT WOS:000320368200016 PM 23429692 ER PT J AU Mai, CL Schreiner, MS Firth, PG Yaster, M AF Mai, Christine L. Schreiner, Mark S. Firth, Paul G. Yaster, Myron TI The development of Pediatric Critical Care Medicine at The Children's Hospital of Philadelphia: an interview with Dr. John J. "Jack' Downes SO PEDIATRIC ANESTHESIA LA English DT Article DE John J; Downes; pediatric critical care medicine; pediatric intensive care unit ID RESPIRATORY-DISTRESS SYNDROME; CHILDHOOD STATUS ASTHMATICUS; POSITIVE AIRWAY PRESSURE; INTENSIVE-CARE; FAILURE; INFANTS; MANAGEMENT; EVOLUTION; NEWBORN AB Dr. John J. Jack' Downes (1930-), the anesthesiologist-in-chief at The Children's Hospital of Philadelphia (1972-1996), has made numerous contributions to pediatric anesthesia and critical care medicine through a broad spectrum of research on chronic respiratory failure, status asthmaticus, postoperative risks of apnea in premature infants, and home-assisted mechanical ventilation. However, his defining moment was in January 1967, when The Children's Hospital of Philadelphia inaugurated its pediatric intensive care unitthe first of its kind in North America. During his tenure, he and his colleagues trained an entire generation of pediatric anesthesiologists and intensivists and set a standard of care and professionalism that continues to the present day. Based on an interview with Dr. Downes, this article reviews a career that advanced pediatric anesthesia and critical care medicine and describes the development of that first pediatric intensive care unit at The Children's Hospital of Philadelphia. C1 [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Crit Care Med, Boston, MA USA. [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pain Med, Boston, MA USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Anesthesiol, Baltimore, MD USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Crit Care Med, Baltimore, MD USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Mai, Christine L.; Firth, Paul G.] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. [Schreiner, Mark S.] Univ Penn, Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Mai, CL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cmai1@partners.org OI Schreiner, Mark/0000-0002-0062-1232 NR 24 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JUL PY 2013 VL 23 IS 7 SI SI BP 655 EP 664 DI 10.1111/pan.12186 PG 10 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 158RX UT WOS:000319991400013 PM 23679061 ER PT J AU Al-Dasooqi, N Sonis, ST Bowen, JM Bateman, E Blijlevens, N Gibson, RJ Logan, RM Nair, RG Stringer, AM Yazbeck, R Elad, S Lalla, RV AF Al-Dasooqi, Noor Sonis, Stephen T. Bowen, Joanne M. Bateman, Emma Blijlevens, Nicole Gibson, Rachel J. Logan, Richard M. Nair, Raj G. Stringer, Andrea M. Yazbeck, Roger Elad, Sharon Lalla, Rajesh V. CA ISOO TI Emerging evidence on the pathobiology of mucositis SO SUPPORTIVE CARE IN CANCER LA English DT Review DE Mucosal injury; Cancer therapy; Targeted drugs; Toxicity; Alimentary tract; Pharmacogenetics ID NF-KAPPA-B; ALIMENTARY-TRACT MUCOSITIS; CYCLOOXYGENASE-2 COX-2 EXPRESSION; TIGHT JUNCTION PERMEABILITY; METASTATIC BREAST-CANCER; PRO-INFLAMMATORY CYTOKINES; STEM-CELL TRANSPLANTATION; INDUCED ORAL MUCOSITIS; DARK AGOUTI RAT; MUCOSAL INJURY AB Considerable progress has been made in our understanding of the biological basis for cancer therapy-induced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. Panel members reviewed the biomedical literature on mucositis pathobiology published between January 2005 and December 2011. Recent research has provided data on the contribution of tissue structure changes, inflammation and microbiome changes to the development of mucositis. Additional research has focused on targeted therapy-induced toxicity, toxicity clustering and the investigation of genetic polymorphisms in toxicity prediction. This review paper summarizes the recent evidence on these aspects of mucositis pathobiology. The ultimate goal of mucositis researchers is to identify the most appropriate targets for therapeutic interventions and to be able to predict toxicity risk and personalize interventions to genetically suitable patients. Continuing research efforts are needed to further our understanding of mucositis pathobiology and the pharmacogenomics of toxicity. C1 [Al-Dasooqi, Noor; Bateman, Emma] Univ Adelaide, Discipline Med, Adelaide, SA 5000, Australia. [Sonis, Stephen T.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bowen, Joanne M.] Univ Adelaide, Discipline Physiol, Adelaide, SA 5000, Australia. [Blijlevens, Nicole] Univ Med Ctr Nijmegen, Dept Haematol, NL-6500HB Nijmegen, Netherlands. [Gibson, Rachel J.] Univ Adelaide, Discipline Anat & Pathol, Adelaide, SA 5000, Australia. [Logan, Richard M.] Univ Adelaide, Sch Dent, Adelaide, SA 5005, Australia. [Nair, Raj G.] Griffith Univ, Discipline Oral Med, Gold Coast, Qld, Australia. [Nair, Raj G.] Queensland Hlth, Dept Haematol & Oncol, Gold Coast, Qld, Australia. [Stringer, Andrea M.; Yazbeck, Roger] Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5000, Australia. [Elad, Sharon] Univ Rochester, Med Ctr, Eastman Inst Oral Hlth, Div Oral Med, Rochester, NY 14642 USA. [Lalla, Rajesh V.] Univ Connecticut, Ctr Hlth, Sect Oral Med, Farmington, CT 06030 USA. [Lalla, Rajesh V.] Univ Connecticut, Ctr Hlth, Neag Comprehens Canc Ctr, Farmington, CT 06030 USA. RP Al-Dasooqi, N (reprint author), Univ Adelaide, Discipline Med, North Terrace, Adelaide, SA 5000, Australia. EM noor.al-dasooqi@adelaide.edu.au RI Yazbeck, Roger/F-3605-2013; Stringer, Andrea/E-9495-2013; Blijlevens, N.M.A./H-8012-2014; Logan, Richard/P-4080-2014; OI Stringer, Andrea/0000-0003-3245-5360; Bowen, Joanne/0000-0003-0876-0031 FU BioAlliance Pharma; Helsinn Healthcare, NA FX This project was carried out as part of the MASCC/ISOO Mucositis Guidelines Update, which was supported by BioAlliance Pharma and Helsinn Healthcare, NA. No industry representatives participated in the development of this manuscript in any way. NR 105 TC 33 Z9 34 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JUL PY 2013 VL 21 IS 7 BP 2075 EP 2083 DI 10.1007/s00520-013-1810-y PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 155ME UT WOS:000319751500035 PM 23604521 ER PT J AU Shin, J Temel, J AF Shin, Jennifer Temel, Jennifer TI Integrating palliative care: when and how? SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE lung cancer; palliative care; supportive care ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; DAILY-LIFE ACTIVITIES; AMBULATORY PATIENTS; CONSULTATION; DYSPNEA; SYMPTOMS; PREVALENCE; EXPERIENCE; ONCOLOGY AB Purpose of review Lung cancer is the leading cause of cancer mortality in men and women. Most patients present with advanced disease and face significant morbidity, with many reporting distressing symptoms throughout the course of their illness. The purpose of this review is to highlight the recent studies that support the integration of early palliative care into the standard oncology care of patients with advanced lung cancer. Recent findings Historically, palliative care was provided predominantly as a hospital-based consultation service; however, recent data support an outpatient delivery model of early palliative care alongside standard oncology care. In two randomized controlled trials, patients with advanced cancer who were assigned to early palliative care reported improved quality of life and mood. Numerous organizations have published guidelines to support the integration of palliative care into the routine care of patients with lung cancer. Summary Palliative care is appropriate for patients at any point in a serious illness. Unlike hospice, palliative care is not limited by prognosis and may be provided at the same time as disease-directed therapies. There is strong evidence underscoring the importance of integrating palliative care across the trajectory of lung cancer. The primary oncology team should routinely assess for pain and other symptoms, and regularly inquire about a patient's understanding of his disease and his goals of care. Specialty palliative care can provide an extra layer of support for patients with lung cancer and their families by helping with more challenging symptom management, psychosocial support, complex decision-making, advance care planning, and transitions in care. C1 [Shin, Jennifer; Temel, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shin, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Lawrence House 307, Boston, MA 02114 USA. EM jashin@partners.org FU National Cancer Institute at the National Institutes of Health [R25CA092203] FX This work was supported by the grant R25CA092203 from the National Cancer Institute at the National Institutes of Health. NR 38 TC 10 Z9 10 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD JUL PY 2013 VL 19 IS 4 BP 344 EP 349 DI 10.1097/MCP.0b013e3283620e76 PG 6 WC Respiratory System SC Respiratory System GA 154GU UT WOS:000319662200003 PM 23715290 ER PT J AU Cai, WL de Moya, M AF Cai, Wenli de Moya, Marc TI Use of multidetector computed tomography to guide management of pneumothorax SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE chest trauma; computerized quantification; multidetector computed tomography; pneumothorax ID BLUNT CHEST TRAUMA; SEVERELY INJURED PATIENTS; OCCULT PNEUMOTHORAX; TUBE THORACOSTOMY; AAST MULTICENTER; COMPLICATIONS; CT; RADIOGRAPH; SIZE; QUANTIFICATION AB Purpose of review Pneumothorax, a potentially life-threatening condition, is present in about one-third of chest trauma patients. Traditionally, pneumothorax has been diagnosed and managed by use of chest radiography, which has been found inaccurate and inconsistent. With the ubiquitous application of multidetector computed tomography (MDCT) in emergency care, MDCT quantification of pneumothoraces becomes an emerging technique for accurate determination of the size of pneumothoraces. The use of MDCT quantification provides a promising means to improve pneumothorax management. Recent findings Recent studies have demonstrated that MDCT is the gold standard for detecting pneumothorax and MDCT provides an effective imaging modality for the accurate measurement of the volume of pneumothoraces. The use of MDCT volumetric quantification of pneumothoraces has been evidenced in the improvement of performance in pneumothorax management for clinically stable chest trauma patients. Summary The MDCT volumetric quantification of pneumothoraces is a new concept in the care of chest trauma patients and has the potential to improve pneumothorax management. Further clinical studies are needed to establish a MDCT-based clinical guideline for pneumothorax management. C1 [Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; de Moya, Marc] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [de Moya, Marc] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St 400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu NR 56 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD JUL PY 2013 VL 19 IS 4 BP 387 EP 393 DI 10.1097/MCP.0b013e32836094be PG 7 WC Respiratory System SC Respiratory System GA 154GU UT WOS:000319662200010 PM 23548888 ER PT J AU Valente, AJ Yoshida, T Clark, RA Delafontaine, P Siebenlist, U Chandrasekar, B AF Valente, Anthony J. Yoshida, Tadashi Clark, Robert A. Delafontaine, Patrice Siebenlist, Ulrich Chandrasekar, Bysani TI Advanced oxidation protein products induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK signaling SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE AOPPs; TRAF3IP2; Oxidative stress; Cell death; Myocardial injury; Free radicals ID GLYCATION END-PRODUCTS; NF-KAPPA-B; ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; NADPH OXIDASE; OXIDIZED LDL; ARTERY-DISEASE; NOX FAMILY; CIKS ACT1; APOPTOSIS AB Advanced oxidation protein products (AOPPs) are formed during chronic oxidative stress as a result of reactions between plasma proteins and chlorinated oxidants. Their levels are elevated during various cardiovascular diseases. Because elevated AOPPs serve as independent risk factors for ischemic heart disease, and cardiomyocyte death is a hallmark of ischemic heart disease, we hypothesized that AOPPs will induce cardiomyocyte death. AOPP-modified mouse serum albumin (AOPP-MSA) induced significant death of neonatal mouse cardiomyocytes that was attenuated by knockdown of the receptor for advanced glycation end products, but not CD36. Notably, TRAF3-interacting protein 2 (TRAF3IP2; also known as CIKS or Act1) knockdown blunted AOPP-induced apoptosis. AOPP-MSA stimulated Nox2/Rac1-dependent superoxide generation, TRAF3IP2 expression, and TRAF3IP2-dependent JNK activation. The superoxide anion generating xanthine/xanthine oxidase system and hydrogen peroxide both induced TRAF3IP2 expression. Further, AOPP-MSA induced mitochondrial Bax translocation and release of cytochrome c into cytoplasm. Moreover, AOPP-MSA suppressed antiapoptotic Bcl-2 and Bcl-xL expression. These effects were reversed by TRAF3IP2 knockdown or forced expression of mutant JNK. Similar to its effects in neonatal cardiomyocytes, AOPP-MSA induced adult cardiomyocyte death in part via TRAF3IP2. These results demonstrate for the first time that AOPPs induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2/JNK activation in vitro and suggest that AOPPs may contribute to myocardial injury in vivo. Thus TRAF3IP2 may represent a potential therapeutic target in ischemic heart disease. (C) 2013 Elsevier Inc. All rights reserved. C1 [Valente, Anthony J.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.; Clark, Robert A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Yoshida, Tadashi; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave, New Orleans, LA 70112 USA. EM bchandra@tulane.edu OI Delafontaine, Patrice/0000-0003-3744-3617; Yoshida, Tadashi/0000-0002-4544-1497 FU Department of Veterans Affairs Research Career Scientist Award; VA Office of Research and Development Biomedical Laboratory Research and Development Service Award [11O1BX000246]; NHLBI/NIH [HL-86787]; NHLBI [HL-70241, HL-80682] FX B.C. is a recipient of the Department of Veterans Affairs Research Career Scientist Award and is supported by VA Office of Research and Development Biomedical Laboratory Research and Development Service Award 11O1BX000246 and NHLBI/NIH Grant HL-86787. The contents of this report do not represent the views of the Department of Veterans Affairs or the U.S. government. PD is supported by NHLBI Grants HL-70241 and HL-80682. NR 49 TC 23 Z9 25 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL PY 2013 VL 60 BP 125 EP 135 DI 10.1016/j.freeradbiomed.2013.02.012 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 151UU UT WOS:000319486500016 PM 23453926 ER PT J AU Zhang, YQ Ikeno, Y Bokov, A Gelfond, J Jaramillo, C Zhang, HM Liu, YH Qi, WB Hubbard, G Richardson, A Van Remmen, H AF Zhang, Yiqiang Ikeno, Yuji Bokov, Alex Gelfond, Jon Jaramillo, Carlos Zhang, Hong-Mei Liu, Yuhong Qi, Wenbo Hubbard, Gene Richardson, Arlan Van Remmen, Holly TI Dietary restriction attenuates the accelerated aging phenotype of Sod1(-/-) mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Dietary restriction; Aging oxidative stress; Cu/ZnSOD; Free radicals ID FATAL NEOPLASTIC DISEASES; DISMUTASE-DEFICIENT MICE; CALORIC RESTRICTION; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; MUSCLE ATROPHY; LIFE-SPAN; DELAYED OCCURRENCE; SHORT-TERM; AGE AB Dietary restriction is a powerful aging intervention that extends the life span of diverse biological species ranging from yeast to invertebrates to mammals, and it has been argued that the antiaging action of dietary restriction occurs through reduced oxidative stress/damage. Using Sod1(-/-) mice, which have previously been shown to have increased levels of oxidative stress associated with a shorter life span and a high incidence of neoplasia, we were able to test directly the ability of dietary restriction to reverse an aging phenotype due to increased oxidative stress/damage. We found that dietary restriction increased the life span of Sod1(-/-) mice 30%, returning it to that of wild-type, control mice fed ad libitum. Oxidative damage in Sod1(-/-) mice was markedly reduced by dietary restriction, as indicated by a reduction in liver and brain F-2-isoprostanes, a marker of lipid peroxidation. Analysis of end of life pathology showed that dietary restriction significantly reduced the overall incidence of pathological lesions in the Sod1(-/-) mice fed the dietary-restricted diet compared to Sod1(-/-) mice fed ad libitum, including the incidence of lymphoma (27 vs 5%) and overall liver pathology. In addition to reduced incidence of overall and liver-specific pathology, the burden and severity of both neoplastic and nonneoplastic lesions was also significantly reduced in the Sod1(-/-) mice fed the dietary-restricted diet. These data demonstrate that dietary restriction can significantly attenuate the accelerated aging phenotype observed in Sod1(-/-) mice that arises from increased oxidative stress/damage. (C) 2013 Elsevier Inc. All rights reserved. C1 [Zhang, Yiqiang; Ikeno, Yuji; Bokov, Alex; Jaramillo, Carlos; Liu, Yuhong; Qi, Wenbo; Hubbard, Gene; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging studies, San Antonio, TX 78229 USA. [Ikeno, Yuji; Hubbard, Gene] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ikeno, Yuji; Richardson, Arlan; Van Remmen, Holly] South Texas Vet Hlth Care Syst, Geriatr Educ Clin & Res Ctr, San Antonio, TX 78229 USA. [Bokov, Alex; Gelfond, Jon] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Zhang, Hong-Mei] Fourth Mil Med Univ, Dept Clin Oncol, Xijing Hosp, Xian 710032, Peoples R China. [Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging studies, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU NIH [P01AG020591]; American Federation for Aging Research FX This study was supported by a NIH grant to H.V.R. and A.R. (P01AG020591) and a Julie Martin Mid-career grant from the American Federation for Aging Research (H.V.R.). NR 43 TC 6 Z9 6 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL PY 2013 VL 60 BP 300 EP 306 DI 10.1016/j.freeradbiomed.2013.02.026 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 151UU UT WOS:000319486500033 PM 23459073 ER EF