FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fonda, JR McGlinchey, RE Rudolph, JL Milberg, WP Hunt, PR Reynolds, MW Yonan, C AF Fonda, J. R. McGlinchey, R. E. Rudolph, J. L. Milberg, W. P. Hunt, P. R. Reynolds, M. W. Yonan, C. TI Burden of pseudobulbar affect (PBA) symptoms in veterans with traumatic brain injury (TBI) SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Fonda, J. R.; McGlinchey, R. E.; Rudolph, J. L.] VA Boston Healthcare Syst, TRACTS Ctr Excellence, Boston, MA USA. [McGlinchey, R. E.; Milberg, W. P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Milberg, W. P.] VA Boston Healthcare Syst, New England GRECC Boston Div, Boston, MA USA. [Hunt, P. R.; Reynolds, M. W.] Evidera, Hlth Econ & Epidemiol, Lexington, MA USA. [Yonan, C.] Avanir Pharmaceut Inc, Hlth Econ & Outcomes Res, Aliso Viejo, CA USA. RI McGlinchey, Regina/R-1971-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAY PY 2014 VL 261 SU 1 MA PP2216 BP S353 EP S353 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AY6KA UT WOS:000347674001144 ER PT J AU Gaertner, J Banwell, B Ghezzi, A Karlsson, G Li, B Merschhemke, M Putzki, N Chitnis, T AF Gaertner, J. Banwell, B. Ghezzi, A. Karlsson, G. Li, B. Merschhemke, M. Putzki, N. Chitnis, T. TI Fingolimod in paediatric multiple sclerosis: design of a double-blind study versus interferon beta-1a IM SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Gaertner, J.] Univ Gottingen, D-37073 Gottingen, Germany. [Banwell, B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Ghezzi, A.] Osped Gallarate, Gallarate, Italy. [Karlsson, G.; Merschhemke, M.; Putzki, N.] Novartis Pharma AG, Basel, Switzerland. [Li, B.] Novartis Pharmaceut, E Hanover, NJ USA. [Chitnis, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAY PY 2014 VL 261 SU 1 MA EP1149 BP S93 EP S93 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AY6KA UT WOS:000347674000248 ER PT J AU Park, D Spencer, JA Lin, CP Scadden, DT AF Park, Dongsu Spencer, Joel A. Lin, Charles P. Scadden, David T. TI Sequential In vivo Imaging of Osteogenic Stem/Progenitor Cells During Fracture Repair SO Jove-Journal of Visualized Experiments LA English DT Article DE Medicine; Issue 87; Osteogenic Stem Cells; In vivo Imaging; Lineage tracking; Bone regeneration; Fracture repair; Mx1 ID BONE; MICE; NICHE AB Bone turns over continuously and is highly regenerative following injury. Osteogenic stem/progenitor cells have long been hypothesized to exist, but in vivo demonstration of such cells has only recently been attained. Here, in vivo imaging techniques to investigate the role of endogenous osteogenic stem/progenitor cells (OSPCs) and their progeny in bone repair are provided. Using osteo-lineage cell tracing models and intravital imaging of induced microfractures in calvarial bone, OSPCs can be directly observed during the first few days after injury, in which critical events in the early repair process occur. Injury sites can be sequentially imaged revealing that OSPCs relocate to the injury, increase in number and differentiate into bone forming osteoblasts. These methods offer a means of investigating the role of stem cell-intrinsic and extrinsic molecular regulators for bone regeneration and repair. C1 [Park, Dongsu; Scadden, David T.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Spencer, Joel A.; Lin, Charles P.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02138 USA. [Spencer, Joel A.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02138 USA. RP Park, D (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. EM dongsu.park@bcm.edu; david_scadden@harvard.edu FU NIAMS [K01AR061434]; Leukemia & Lymphoma Society [5127-09]; National Institutes of Health FX We thank C. Park for reading the manuscript. This work was supported by the NIAMS under Award Number K01AR061434 and a Leukemia & Lymphoma Society Fellowship Award (5127-09) to D.P and grants of the National Institutes of Health to C.P.L. and D.T.S. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 17 TC 0 Z9 0 U1 0 U2 1 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAY PY 2014 IS 87 AR e51289 DI 10.3791/51289 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA4VV UT WOS:000348905400029 ER PT J AU Song, BJ Caprioli, J AF Song, Brian J. Caprioli, Joseph TI New directions in the treatment of normal tension glaucoma SO INDIAN JOURNAL OF OPHTHALMOLOGY LA English DT Review DE Intraocular pressure; low tension glaucoma; neuroprotection; normal tension glaucoma; risk factors ID OPEN-ANGLE GLAUCOMA; CEREBROSPINAL-FLUID PRESSURE; GINKGO-BILOBA EXTRACT; NONPENETRATING DEEP SCLERECTOMY; NECROSIS-FACTOR-ALPHA; SLEEP-APNEA SYNDROME; NOCTURNAL INTRAOCULAR-PRESSURE; ENDOTHELIN-1 PLASMA-LEVELS; OCULAR PERFUSION-PRESSURE; ACTIVE CALCIUM-ANTAGONIST AB Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans. C1 [Song, Brian J.; Caprioli, Joseph] Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. [Song, Brian J.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. RP Caprioli, J (reprint author), Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM caprioli@jsei.ucla.edu OI Caprioli, Joseph/0000-0002-2383-7263 NR 146 TC 11 Z9 11 U1 0 U2 6 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0301-4738 EI 1998-3689 J9 INDIAN J OPHTHALMOL JI Indian J. Ophthalmol. PD MAY PY 2014 VL 62 IS 5 BP 529 EP 537 DI 10.4103/0301-4738.133481 PG 9 WC Ophthalmology SC Ophthalmology GA AZ9WG UT WOS:000348564100002 PM 24881596 ER PT J AU Wasserman, M Renfrew, MR Green, AR Lopez, L Tan-McGrory, A Brach, C Betancourt, JR AF Wasserman, Melanie Renfrew, Megan R. Green, Alexander R. Lopez, Lenny Tan-McGrory, Aswita Brach, Cindy Betancourt, Joseph R. TI Identifying and Preventing Medical Errors in Patients With Limited English Proficiency: Key Findings and Tools for the Field SO JOURNAL FOR HEALTHCARE QUALITY LA English DT Article DE patient safety; performance improvement; quality improvement; research-qualitative AB Since the 1999 Institute of Medicine (IOM) report To Err is Human, progress has been made in patient safety, but few efforts have focused on safety in patients with limited English proficiency (LEP). This article describes the development, content, and testing of two new evidence-based Agency for Healthcare Research and Quality (AHRQ) tools for LEP patient safety. In the content development phase, a comprehensive mixed-methods approach was used to identify common causes of errors for LEP patients, high-risk scenarios, and evidence-based strategies to address them. Based on our findings, Improving Patient Safety Systems for Limited English Proficient Patients: A Guide for Hospitals contains recommendations to improve detection and prevention of medical errors across diverse populations, and TeamSTEPPS Enhancing Safety for Patients with Limited English Proficiency Module trains staff to improve safety through team communication and incorporating interpreters in the care process. The Hospital Guide was validated with leaders in quality and safety at diverse hospitals, and the TeamSTEPPS LEP module was field-tested in varied settings within three hospitals. Both tools were found to be implementable, acceptable to their audiences, and conducive to learning. Further research on the impact of the combined use of the guide and module would shed light on their value as a multifaceted intervention. C1 [Wasserman, Melanie] Abt Associates Inc, Cambridge, MA 02138 USA. [Renfrew, Megan R.] Massachusetts Gen Hosp Phys Org, Charlestown, MA USA. [Renfrew, Megan R.; Green, Alexander R.; Lopez, Lenny; Tan-McGrory, Aswita] Dispar Solut Ctr, Baltimore, MD USA. [Green, Alexander R.; Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Green, Alexander R.] Harvard Univ, Sch Med, Cross Cultural Care Comm, Cambridge, MA 02138 USA. [Lopez, Lenny] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lopez, Lenny] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Brach, Cindy] Agcy Healthcare Res & Qual, New York, NY USA. [Betancourt, Joseph R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Betancourt, Joseph R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wasserman, M (reprint author), Abt Associates Inc, Cambridge, MA 02138 USA. EM melanie_wasserman@abtassoc.com FU Intramural AHRQ HHS [HS999999] NR 16 TC 3 Z9 3 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1062-2551 EI 1945-1474 J9 J HEALTHC QUAL JI J. Healthc. Qual. PD MAY-JUN PY 2014 VL 36 IS 3 BP 5 EP 16 DI 10.1111/jhq.12065 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AZ8FK UT WOS:000348450200001 PM 24629098 ER PT J AU Winans-Mitrik, RL Hula, WD Dickey, MW Schumacher, JG Swoyer, B Doyle, PJ AF Winans-Mitrik, Ronda L. Hula, William D. Dickey, Michael W. Schumacher, James G. Swoyer, Brooke Doyle, Patrick J. TI Description of an Intensive Residential Aphasia Treatment Program: Rationale, Clinical Processes, and Outcomes SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE aphasia; outcomes; response to intervention; stroke; effectiveness ID HEALTH-CARE UTILIZATION; RURAL REGION; THERAPY; ADULTS; REHABILITATION; EFFICACY; ACCESS; FORMS; MODEL AB Purpose: The purpose of this article is to describe the rationale, clinical processes, and outcomes of an intensive comprehensive aphasia program (ICAP). Method: Seventy-three community-dwelling adults with aphasia completed a residentially based ICAP. Participants received 5 hr of daily 1:1 evidence-based cognitivelinguistically oriented aphasia therapy, supplemented with weekly socially oriented and therapeutic group activities over a 23-day treatment course. Standardized measures of aphasia severity and communicative functioning were obtained at baseline, program entry, program exit, and follow-up. Results were analyzed using a Bayesian latent growth curve model with 2 factors representing (a) the initial level and (b) change over time, respectively, for each outcome measure. Results: Model parameter estimates showed reliable improvement on all outcome measures between the initial and final assessments. Improvement during the treatment interval was greater than change observed across the baseline interval, and gains were maintained at follow-up on all measures. Conclusions: The rationale, clinical processes, and outcomes of a residentially based ICAP have been described. ICAPs differ with respect to treatments delivered, dosing parameters, and outcomes measured. Specifying the defining components of complex interventions, establishing their feasibility, and describing their outcomes are necessary to guide the development of controlled clinical trials. C1 [Winans-Mitrik, Ronda L.; Hula, William D.; Dickey, Michael W.; Schumacher, James G.; Swoyer, Brooke; Doyle, Patrick J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Hula, William D.; Dickey, Michael W.; Doyle, Patrick J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. EM patrick.doyle@va.gov NR 57 TC 7 Z9 7 U1 7 U2 18 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 EI 1558-9110 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY PY 2014 VL 23 IS 2 BP 330 EP 342 DI 10.1044/2014_AJSLP-13-0102 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AU5ZP UT WOS:000345682200019 PM 24687159 ER PT J AU Post, JB Morin, KG Handrakis, JP Rivera, DR Yen, C Sano, M Spungen, AM AF Post, James B. Morin, Kel G. Handrakis, John P. Rivera, Dwindally Rosado Yen, Christina Sano, Mary Spungen, Ann M. TI Cognition may be related to arterial pulsatility index in HD patients SO CLINICAL NEPHROLOGY LA English DT Article DE pulsatility; cognitive impairment; hemodialysis ID HEMODIALYSIS-PATIENTS; RENAL-DISEASE; CAROTID-ARTERY; IMPAIRMENT; HYPERPARATHYROIDISM; MICROANGIOPATHY AB Aims: Hemodialysis (HD) patients have a heavy burden of subclinical cerebrovascular disease and cognitive changes consistent with a vascular etiology. Pulsatility index is associated with microangiopathy of cerebral blood vessels and an increased risk of cerebral infarction. The proposed study was to determine common carotid artery pulsatility index (CCAPI) and its relation to cognition in well-dialyzed HD patients with no history of stroke or dementia and matched controls. Methods: Observational, cross-sectional study of CCAPI and cognition in 37 hemodialysis outpatients and 18 matched controls with normal kidney function. Non-parametric analyses were used to compare variables between groups. Multiple regression and ANOVA models were used to adjust for risk factor differences. Results: Controls had a lower CCAPI than the HD group (1.7 +/- 0.3 vs. 2.1 +/- 0.4 cm/s, p = 0.006). HD patients scored significantly lower on all cognitive domains. Attention correlated with CCAPI in HD patients, independent of hypertension, diabetes, hyperlipidemia, and years on HD (r(2) = -0.36, p = 0.01). CCAPI correlated with years on HD, independent of traditional cardiovascular risk factors. (r(2) = 0.26, p = 0.04). Conclusion: In well-dialyzed hemodialysis patients with no history of stroke or dementia, -CCAPI may correlate with cognitive function and represent a marker for underlying cerebral microvascular disease. C1 [Post, James B.] James J Peters VA Med Ctr, Div Nephrol, Bronx, NY 10468 USA. [Post, James B.; Morin, Kel G.; Handrakis, John P.; Rivera, Dwindally Rosado; Yen, Christina; Spungen, Ann M.] James J Peters VA Med Ctr, VA RR&D Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA. [Handrakis, John P.] New York Inst Technol, Sch Hlth Professionals, Dept Phys Therapy, Old Westbury, NY 11568 USA. [Sano, Mary] James J Peters VA Med Ctr, VA RR&D, Bronx, NY 10468 USA. [Post, James B.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabilitat Med, New York, NY USA. RP Post, JB (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM James.Post@va.gov FU VA RRD CDA 2 [B5050W]; VA RR&D Center of Excellence [B4162C] FX This project was funded by the VA RR&D CDA 2 #B5050W and VA RR&D Center of Excellence #B4162C. We would like to thank the kidney dialysis unit nursing staff for assisting with patient scheduling and communication. NR 30 TC 2 Z9 2 U1 1 U2 5 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD MAY PY 2014 VL 81 IS 5 BP 313 EP 319 DI 10.5414/CN107998 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AT2WQ UT WOS:000344795400002 PM 24780553 ER PT J AU Begum, SR Shaheen, N Goodman, A Nahar, S Rahman, AKMA Ahmed, MU AF Begum, S. R. Shaheen, N. Goodman, A. Nahar, S. Rahman, A. K. M. A. Ahmed, M. U. TI EPIDEMIOLOGY AND SCREENING OF CERVICAL CANCER OF RURAL WOMEN AND URBAN COMMERCIAL SEX WORKER IN SELECTED AREAS OF BANGLADESH SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Begum, S. R.; Shaheen, N.; Nahar, S.] Sq Hosp Ltd, Obstet & Gynaecol, Dhaka, Bangladesh. [Goodman, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rahman, A. K. M. A.; Ahmed, M. U.] Bangladesh Agr Univ, Dept Med, Mymensingh, Bangladesh. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY PY 2014 VL 24 SU 1 MA IGCS-0242 BP 24 EP 25 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AT0EU UT WOS:000344610900014 ER PT J AU Jylanki, P Nummenmaa, A Vehtari, A AF Jylanki, Pasi Nummenmaa, Aapo Vehtari, Aki TI Expectation Propagation for Neural Networks with Sparsity-Promoting Priors SO JOURNAL OF MACHINE LEARNING RESEARCH LA English DT Article DE expectation propagation; neural network; multilayer perceptron; linear model; sparse prior; automatic relevance determination ID GAUSSIAN PROCESS CLASSIFICATION; LIKELIHOOD; INFERENCE; MODELS AB We propose a novel approach for nonlinear regression using a two-layer neural network (NN) model structure with sparsity-favoring hierarchical priors on the network weights. We present an expectation propagation (EP) approach for approximate integration over the posterior distribution of the weights, the hierarchical scale parameters of the priors, and the residual scale. Using a factorized posterior approximation we derive a computationally efficient algorithm, whose complexity scales similarly to an ensemble of independent sparse linear models. The approach enables flexible definition of weight priors with different sparseness properties such as independent Laplace priors with a common scale parameter or Gaussian automatic relevance determination (ARD) priors with different relevance parameters for all inputs. The approach can be extended beyond standard activation functions and NN model structures to form flexible nonlinear predictors from multiple sparse linear models. The effects of the hierarchical priors and the predictive performance of the algorithm are assessed using both simulated and real-world data. Comparisons are made to two alternative models with ARD priors: a Gaussian process with a NN covariance function and marginal maximum a posteriori estimates of the relevance parameters, and a NN with Markov chain Monte Carlo integration over all the unknown model parameters. C1 [Jylanki, Pasi; Vehtari, Aki] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, FI-00076 Aalto, Finland. [Nummenmaa, Aapo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Jylanki, P (reprint author), Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, POB 12200, FI-00076 Aalto, Finland. EM pasi.jylanki@aalto.fi; nummenma@nmr.mgh.harvard.edu; aki.vehtari@aalto.fi FU Academy of Finland [218248] FX We thank the anonymous referees for their helpful feedback and suggestions. The research reported in this publication was partially funded by the Academy of Finland (grant 218248). NR 44 TC 0 Z9 0 U1 3 U2 3 PU MICROTOME PUBL PI BROOKLINE PA 31 GIBBS ST, BROOKLINE, MA 02446 USA SN 1532-4435 J9 J MACH LEARN RES JI J. Mach. Learn. Res. PD MAY PY 2014 VL 15 BP 1849 EP 1901 PG 53 WC Automation & Control Systems; Computer Science, Artificial Intelligence SC Automation & Control Systems; Computer Science GA AT0PQ UT WOS:000344638100007 ER PT J AU Busby, AK Reese, RL Simon, SR AF Busby, Andrea K. Reese, Rebecca L. Simon, Steven R. TI Pulmonary Rehabilitation Maintenance Interventions: A Systematic Review SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Review DE exercise; physical activity; chronic obstructive pulmonary disease; behavior change ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; HOME-BASED EXERCISE; LONG-TERM BENEFITS; PHYSICAL-ACTIVITY; FOLLOW-UP; BEHAVIOR-CHANGE; OLDER-ADULTS; DISEASE; PROGRAM AB Objective: To examine existing research on pulmonary exercise rehabilitation (PR) maintenance interventions. Methods: Authors conducted a systematic review of PR maintenance interventions. The primary outcome of interest was physical endurance. Results: Eight studies met inclusion criteria. Most showed initial positive intervention effects, which declined to non-significance within 3-12 months after completion of maintenance. Only one of the 8 studies described a theoretical framework underlying the maintenance intervention. Conclusions: Existing interventions generally fail to maintain benefits derived from PR programs. Future studies should evaluate maintenance interventions that are theoretically-based and seek to impact known maintenance mediators. Evaluation of these interventions should include substantial follow-up periods and adherence measurements. C1 [Busby, Andrea K.] VA Boston Healthcare Syst, Emergency Serv, Boston, MA USA. [Reese, Rebecca L.] VA Boston Healthcare Syst, Behav Med Serv, Boston, MA USA. [Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. RP Busby, AK (reprint author), Miriam Hosp, Behav Med Clin Serv, Lifespan Phys Grp, Providence, RI 02906 USA. EM abusby@lifespan.org FU NHLBI NIH HHS [T32 HL007456] NR 57 TC 3 Z9 3 U1 0 U2 10 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAY PY 2014 VL 38 IS 3 BP 321 EP 330 DI 10.5993/AJHB.38.3.1 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AS1JB UT WOS:000344036300001 PM 24636028 ER PT J AU Manchikanti, L Falco, FJE Benyamin, RM Kaye, AD Boswell, MV Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Benyamin, Ramsin M. Kaye, Alan D. Boswell, Mark V. Hirsch, Joshua A. TI A Modified Approach to Grading of Evidence SO PAIN PHYSICIAN LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; MANAGEMENT SPECIFIC INSTRUMENT; UPDATED METHOD GUIDELINES; LOW-BACK-PAIN; SYSTEMATIC REVIEWS; INTERVENTIONAL TECHNIQUES; METHODOLOGIC QUALITY; RANDOMIZED-TRIALS; TASK-FORCE; RECOMMENDATION C1 [Manchikanti, Laxmaiah] Pain Management Ctr, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 41 TC 21 Z9 21 U1 1 U2 1 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2014 VL 17 IS 3 BP E319 EP E325 PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AS7EZ UT WOS:000344421300013 PM 24850113 ER PT J AU Manchikanti, L Hirsch, JA Heavner, JE Cohen, SP Benyamin, RM Sehgal, N Falco, FJE Vallejo, R Onyewu, O Zhu, J Kaye, AD Boswell, MV Helm, S Candido, KD Diwan, S Simopoulos, TT Singh, V Pampati, V Racz, GB Raj, PP AF Manchikanti, Laxmaiah Hirsch, Joshua A. Heavner, James E. Cohen, Steven P. Benyamin, Ramsin M. Sehgal, Nalini Falco, Frank J. E. Vallejo, Ricardo Onyewu, Obi Zhu, Jie Kaye, Alan D. Boswell, Mark V. Helm, Standiford, II Candido, Kenneth D. Diwan, Sudhir Simopoulos, Thomas T. Singh, Vijay Pampati, Vidyasagar Racz, Gabor B. Raj, P. Prithvi TI Development of an Interventional Pain Management Specific Instrument for Methodologic Quality Assessment of Nonrandomized Studies of Interventional Techniques SO PAIN PHYSICIAN LA English DT Article DE Methodological quality assessment; evidence-based medicine; comparative effectiveness research; Cochrane Reviews; interventional techniques; risk of bias assessment; nonrandomized trials; observational studies ID LOW-BACK-PAIN; CONFLICTS-OF-INTEREST; VERTEBRAL COMPRESSION FRACTURES; 2-YEAR FOLLOW-UP; INTERLAMINAR EPIDURAL INJECTIONS; ACTIVE-CONTROL TRIAL; CLINICALLY IMPORTANT DIFFERENCE; RANDOMIZED-CONTROLLED-TRIALS; ARTERY-BYPASS-SURGERY; UPDATED METHOD GUIDELINES AB Background: The major component of a systematic review is assessment of the methodologic quality and bias of randomized and nonrandomized trials. While there are multiple instruments available to assess the methodologic quality and bias for randomized controlled trials (RCTs), there is a lack of extensively utilized instruments for observational studies, specifically for interventional pain management (IPM) techniques. Even Cochrane review criteria for randomized trials is considered not to be a "gold standard," but merely an indication of the current state of the art review methodology. Recently a specific instrument to assess the methodologic quality of randomized trials has been developed for interventional techniques. Objectives: Our objective was to develop an IPM specific instrument to assess the methodological quality of nonrandomized trials or observational studies of interventional techniques. Methods: The item generation for the instrument was based on a definition of quality, to the extent to which the design and conduct of the trial were congruent with the objectives of the study. Applicability was defined as the extent to which procedures produced by the study could be applied using contemporary IPM techniques. Multiple items based on Cochrane review criteria and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) were utilized. Results: A total of 16 items were developed which formed the IPM-QRBNR tool. The assessment was performed in multiple stages. The final assessment was 4 nonrandomized studies. The inter-rater agreement was moderate to good for IPM-QRBNR criteria. Limitations: Limited validity or accuracy assessment of the instrument and the large number of items to be scored were limitations. Conclusion: We have developed a new comprehensive instrument to assess the methodological quality of nonrandomized studies of interventional techniques. This instrument provides extensive information specific to interventional techniques is useful in assessing the methodological quality and bias of observational studies of interventional techniques. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Heavner, James E.; Racz, Gabor B.; Raj, P. Prithvi] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Cohen, Steven P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Cohen, Steven P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Sehgal, Nalini] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Falco, Frank J. E.; Onyewu, Obi; Zhu, Jie] Mid Atlantic Spine Pain Phys, Newark, DE USA. [Falco, Frank J. E.; Onyewu, Obi; Zhu, Jie] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Vallejo, Ricardo] Millennium Pain Ctr, Bloomington, IL USA. [Vallejo, Ricardo] Illinois State Univ, Normal, IL 61761 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Candido, Kenneth D.] Advocate Illinois Mason Med Ctr, Dept Anesthesiol, Chicago, IL USA. [Diwan, Sudhir] Manhattan Spine & Pain Med, New York, NY USA. [Simopoulos, Thomas T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; BioDelivery Sciences International, Inc.; Mundipharma Research GmbH Co.; AstraZeneca; Purdue Pharma, LP; Theravance FX Dr. Vallejo receives research support from Cephalon/Teva, BioDelivery Sciences International, Inc., Mundipharma Research GmbH & Co., AstraZeneca, Purdue Pharma, LP, and Theravance, and is a consultant for Nevro and Kymberly-Clark.; Dr. Helm is a clinical investigator with Epimed and receives research support from Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. He has attended an advisory group meeting for Activas. NR 313 TC 11 Z9 11 U1 1 U2 9 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2014 VL 17 IS 3 BP E291 EP E317 PG 27 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AS7EZ UT WOS:000344421300012 PM 24850112 ER PT J AU Manchikanti, L Hirsch, JA Cohen, SP Heavner, JE Falco, FJE Diwan, S Boswell, MV Candido, KD Onyewu, O Zhu, J Sehgal, N Kaye, AD Benyamin, RM Helm, S Singh, V Datta, S Abdi, S Christo, PJ Hameed, H Hameed, M Vallejo, R Pampati, V Racz, GB Raj, PP AF Manchikanti, Laxmaiah Hirsch, Joshua A. Cohen, Steven P. Heavner, James E. Falco, Frank J. E. Diwan, Sudhir Boswell, Mark V. Candido, Kenneth D. Onyewu, Obi Zhu, Jie Sehgal, Nalini Kaye, Alan D. Benyamin, Ramsin M. Helm, Standiford, II Singh, Vijay Datta, Sukdeb Abdi, Salahadin Christo, Paul J. Hameed, Haroon Hameed, Mariam Vallejo, Ricardo Pampati, Vidyasagar Racz, Gabor B. Raj, P. Prithvi TI Assessment of Methodologic Quality of Randomized Trials of Interventional Techniques: Development of an Interventional Pain Management Specific Instrument SO PAIN PHYSICIAN LA English DT Article DE Methodological quality assessment; evidence-based medicine; comparative effectiveness research; Cochrane Reviews; interventional techniques; risk of bias assessment ID LOW-BACK-PAIN; CONFLICTS-OF-INTEREST; 2-YEAR FOLLOW-UP; INTERLAMINAR EPIDURAL INJECTIONS; ACTIVE-CONTROL TRIAL; CLINICALLY IMPORTANT DIFFERENCE; UPDATED METHOD GUIDELINES; SAMPLE-SIZE CALCULATION; JOINT NERVE BLOCKS; HEALTH-CARE INTERVENTIONS AB Background: A major component of a systematic review is an assessment of the methodological quality and bias of randomized trials. The most commonly utilized methodological quality assessment and bias assessment for randomized trials is by the Cochrane Review Group. While this is not a "gold standard," it is an indication of the current state-of-the-art review methodology. There is, however, no specific instrument to assess the methodological quality of manuscripts published for interventional techniques. Objectives: Our objective was to develop an instrument specifically for interventional pain management, to assess the methodological quality of randomized trials of interventional techniques. Methods: Item generation for the instrument was based on a definition of quality, to the extent to which the design and conduct of the trial were congruent with the objectives of the trial. Applicability was defined as the extent to which the trial produced procedures could be applied with contemporary interventional pain management techniques. Multiple items based on Cochrane review criteria were utilized along with specific requirements for interventional techniques. Results: A total of 22 items were developed which formed IPM-QRB or Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment tool. This included 9 of the 12 items from the Cochrane review criteria with definition of some items that were repetitive or duplicate, and the addition of 13 new items. The results were compared for inter-rater reliability of Cochrane review criteria and IPM-QRB, and inter-instrument reliability. The assessment was performed in multiple stages with an initial learning curve. The final assessment was for 4 randomized controlled trials (RCTs) utilizing both Cochrane review criteria and IPM-QRB criteria. The inter-rater agreement for Cochrane review criteria with overall intra-class correlation coefficient was 0.407 compared to an intra-class correlation coefficient of 0.833 for IPM-QRB criteria. The inter-rater agreement was superior for IPM-QRB criteria compared to Cochrane review criteria despite twice the items of Cochrane review criteria as IPM-QRB criteria with the detailed nature of assessment. Limitations: Limited validity or accuracy assessment of the instrument and the large number of items to be scored. Conclusion: We have developed a new comprehensive instrument to assess the methodological quality of randomized trials of interventional techniques. This instrument is superior to Cochrane review methodology criteria in that it provides more extensive and specific information for interventional techniques that will be useful in assessing the methodologic quality and bias of interventional techniques. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Cohen, Steven P.; Christo, Paul J.; Hameed, Mariam] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Cohen, Steven P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Heavner, James E.; Racz, Gabor B.; Raj, P. Prithvi] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Falco, Frank J. E.; Onyewu, Obi; Zhu, Jie] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.; Onyewu, Obi; Zhu, Jie] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Diwan, Sudhir] Manhattan Spine & Pain Med, New York, NY USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Candido, Kenneth D.] Advocate Illinois Masonic Med Ctr, Dept Anesthesiol, Chicago, IL USA. [Sehgal, Nalini] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Benyamin, Ramsin M.; Vallejo, Ricardo] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.; Vallejo, Ricardo] Univ Illinois, Urbana, IL 61801 USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Datta, Sukdeb] Laser Spine Pain Inst, New York, NY USA. [Datta, Sukdeb] Mt Sinai Sch Med, New York, NY USA. [Abdi, Salahadin] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Christo, Paul J.] Blaustein Pain Treatment Ctr, Baltimore, MD USA. [Hameed, Haroon] Spine Care Ctr, Manassas, VA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; AstraZeneca; Purdue Pharma, LP; Sucampo Pharmaceuticals; BioDelivery Sciences International, Inc.; Mundipharma Research GmbH Co.; Theravance FX Dr. Cohen served as a paid co-investigator on a Department of Defense study. He is also a consultant for Halozyme and Kimberly Clark. Dr. Falco is a consultant for St. Jude Medical Inc. and Joimax Inc. Dr. Kaye is a speaker for Depomed, Inc. Dr. Benyamin is a consultant and lecturer for Boston Scientific and Kimberly Clark. Dr. Helm is a clinical investigator with Epimed and receives research support from Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. He has attended an advisory group meeting for Activas. Dr. Datta receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew. Dr. Vallejo receives research support from Cephalon/Teva, BioDelivery Sciences International, Inc., Mundipharma Research GmbH & Co., AstraZeneca, Purdue Pharma, LP, and Theravance, and is a consultant for Nevro and Kymberly-Clark. Dr. Racz is a Consultant for and has family ownership of Epimed International, is a Consultant to Cosman RF Company, and has Medtronic patent issues. NR 244 TC 21 Z9 21 U1 2 U2 8 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2014 VL 17 IS 3 BP E263 EP E290 PG 28 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AS7EZ UT WOS:000344421300011 PM 24850111 ER PT J AU Habibollahi, P Waldron, T Heidari, P Cho, HS Alcantara, D Josephson, L Wang, TC Rustgi, AK Mahmood, U AF Habibollahi, Peiman Waldron, Todd Heidari, Pedram Cho, Hoon Sung Alcantara, David Josephson, Lee Wang, Timothy C. Rustgi, Anil K. Mahmood, Umar TI Fluorescent Nanoparticle Imaging Allows Noninvasive Evaluation of Immune Cell Modulation in Esophageal Dysplasia SO MOLECULAR IMAGING LA English DT Article ID TUMOR MICROENVIRONMENT; SUPPRESSOR-CELLS; MYELOID CELLS; CANCER; INFLAMMATION; P120-CATENIN; MACROPHAGES AB Esophageal tumors provide unique challenges and opportunities for developing and testing surveillance imaging technology for different tumor microenvironment components, including assessment of immune cell modulation, with the ultimate goal of promoting early detection and response evaluation. In this context, accessibility through the lumen using a minimally invasive approach provides a means for repetitive evaluation longitudinally by combining fluorescent endoscopic imaging technology with novel fluorescent nanoparticles that are phagocytized by immune cells in the microenvironment. The agent we developed for imaging is synthesized from Feraheme (ferumoxytol), a Food and Drug Administration-approved monocrystaline dextran-coated iron oxide nanoparticle, which we conjugated to a near-infrared fluorochrome, CyAL5.5. We demonstrate a high level of uptake of the fluorescent nanoparticles by myeloid-derived suppressor cells (MDSCs) in the esophagus and spleen of L2Cre;p120ctn(flox/flox) mice. These mice develop esophageal dysplasia leading to squamous cell carcinoma; we have previously demonstrated that dysplastic and neoplastic esophageal lesions in these mice have an immune cell infiltration that is dominated by MDSCs. In the L2Cre; p120ctn(flox/flox) mice, evaluation of the spleen reveals that nearly 80% of CD45(+) leukocytes that phagocytized the nanoparticle were CD11b(+)Gr1(+) MDSCs. After dexamethasone treatment, we observed concordant decreased fluorescent signal from esophageal lesions during fluorescent endoscopy and decreased CyAL5.5-fluorescent-positive immune cell infiltration in esophageal dysplastic lesions by fluorescence-activated cell sorting analysis. Our observations suggest that this translatable technology may be used for the early detection of dysplastic changes and the serial assessment of immunomodulatory therapy and to visualize changes in MDSCs in the esophageal tumor microenvironment. C1 [Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. Univ Penn, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Dept Genet, Philadelphia, PA 19104 USA. Columbia Univ, Med Ctr, Dept Med, Div Digest & Liver Dis, New York, NY USA. Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU National Institutes of Health (NIH) [U01CA143056, U01CA084301, P50CA127003]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T32-DK007066]; NIH [F32-CA162719]; NIH/National Cancer Institute [P01-CA098101]; NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases [P30DK050306] FX Financial disclosure of authors: This research was supported in part by National Institutes of Health (NIH) grants U01CA143056 (to U. Mahmood, T.C. Wang, A.K. Rustgi), U01CA084301 (to U. Mahmood), and P50CA127003 (to U. Mahmood). This work was also supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32-DK007066 (to T.C. Wang), NIH F32-CA162719 (to T.C. Wang), NIH/National Cancer Institute P01-CA098101 (to T.C. Wang, A.K. Rustgi), and the NIH/NIDDK P30DK050306 Center for Molecular Studies in Digestive and Liver Diseases (and its Molecular Pathology and Imaging, Molecular Biology, Cell Culture, and Mouse Core facilities). NR 25 TC 2 Z9 2 U1 5 U2 9 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD MAY PY 2014 VL 13 IS 3 DI 10.2310/7290.2014.00003 PG 11 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA AS4AF UT WOS:000344215300002 PM 24824854 ER PT J AU Feeney, MP Stover, B Keefe, DH Garinis, AC Day, JE Seixas, N AF Feeney, M. Patrick Stover, Bert Keefe, Douglas H. Garinis, Angela C. Day, Jessica E. Seixas, Noah TI Sources of Variability in Wideband Energy Reflectance Measurements in Adults SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Wideband acoustic immittance; energy or power reflectance; absorbance; middle ear; tympanometry ID MIDDLE-EAR DISORDERS; NORMAL-HEARING; OTOACOUSTIC EMISSIONS; ACOUSTIC-IMPEDANCE; OTOSCLEROTIC EARS; TYMPANOMETRY; COEFFICIENT; CHILDREN; INFANTS AB Background: Wideband acoustic immittance measurements of the middle ear, such as wideband energy reflectance (ER), can provide information about how the middle ear functions across the traditional audiometric frequency range. These measurements are being investigated as a new means of evaluating conductive hearing disorders, and studies have been reported on a number of middle-ear disorders. However, the normative database for wideband ER is still being developed, and more information is needed about sources of test variability. Purpose: The purpose of the present study was to evaluate sources of variability in wideband ER measurements at baseline and across annual tests for up to 5 yr in subjects with normal hearing. Study Sample: The main group consisted of 112 subjects (187 ears), 24 females and 88 males, with normal hearing and normal 0.226-kHz admittance tympanometry. An additional 24 adults with abnormal 0.226-kHz tympanometry provided baseline comparison data. Research Design: A longitudinal design was used in obtaining annual measurements of audiometry, tympanometry, and wideband ER at ambient pressure in adults. Data Collection and Analysis: Clinical audiometry and tympanometry data and 1/3-octave wideband ER measurements were obtained at baseline and annually for up to four additional tests. Descriptive statistics and t-tests were used to explore differences in 1/3-octave baseline ER measures in terms of subject age, test ear, sex, and clinical tympanometry. Longitudinal mixed-effects linear regression models at 1.0, 2.0, and 4.0 kHz were used to examine the different sources of variance affecting ER over time. Results: There were small but statistically significant mean differences in ER for baseline measurements as a function of ear, sex, and age. Compared with these results, data for 29 ears with abnormal 0.226-kHz tympanometry differed from mean normal data across a broad frequency range by as much as 20%. ER varied as a function of peak compensated static acoustic admittance (Y-tm) for measures at 1.0 kHz but was unrelated to Ytm at 2.0 and 4.0 kHz. ER also varied as a function of the test ear, with significantly higher ER on the left at 1.0 and 2.0 kHz, but was not significantly related to the test ear at 4.0 kHz. The standard deviation for test-retest variability was about 0.1 at each frequency, which is consistent with previous studies. Conclusions: Mean wideband ER at baseline showed small but significant differences related to sex, ear, and age. ER was significantly related to Y-tm at 1.0 kHz in the longitudinal data but not at 2.0 or 4.0 kHz and to the test ear at 1.0 and 2.0 kHz but not at 4.0 kHz. When evaluated at ambient pressure, ER for ears with negative middle-ear pressure was similar to that of ears with abnormally low Y-tm. Therefore it might be necessary to evaluate wideband acoustic immittance compensated for middle-ear pressure by using tympanometry to obtain an effective differential diagnosis of middle-ear disorders in adults. C1 [Feeney, M. Patrick; Garinis, Angela C.] Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. [Feeney, M. Patrick] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Feeney, M. Patrick] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Stover, Bert] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Keefe, Douglas H.] Boys Town Natl Res Hosp, Omaha, NE 68131 USA. [Day, Jessica E.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. RP Feeney, MP (reprint author), Portland VA Med Ctr, NCRAR, VA RR&D Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Patrick.Feeney@va.gov FU National Institute for Occupational Health and Safety of the US Centers for Disease Control and Prevention [5 R01 0H003912]; VA RRD award [C9230C] FX This research was funded by the National Institute for Occupational Health and Safety of the US Centers for Disease Control and Prevention, 5 R01 0H003912. Support for the first author was also provided by VA RR&D award C9230C. The content of this article does not represent the views of the Department of Veterans Affairs or of the United States Government. NR 30 TC 3 Z9 3 U1 2 U2 11 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD MAY PY 2014 VL 25 IS 5 SI SI BP 449 EP 461 DI 10.3766/jaaa.25.5.4 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AQ7RX UT WOS:000343018000004 PM 25257719 ER PT J AU Feeney, MP Sanford, CA Putterman, DB AF Feeney, M. Patrick Sanford, Chris A. Putterman, Daniel B. TI Effects of Ear-Canal Static Pressure on Pure-Tone Thresholds and Wideband Acoustic Immittance SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Wideband acoustic immittance; middle ear; conductive hearing loss; otitis media ID CONDUCTIVE HEARING-LOSS; REFLECTION COEFFICIENT; OTOACOUSTIC EMISSIONS; HUMAN INFANTS; IMPEDANCE; ADULTS; IDENTIFICATION; PRESSURIZATION; TYMPANOMETRY; ADMITTANCE AB Background: Wideband acoustic immittance (WAI) measures provide information about middle-ear function across the traditional audiometric frequency range from 0.25 to 8.0 kHz. Recent studies have found that WAI is effective in predicting the presence of conductive hearing loss (CHL). It is not known whether WAI can accurately estimate the degree of threshold shift caused by CHL. Purpose: The purpose of the present study was to evaluate the relationship between changes in puretone threshold and changes in wideband absorbance and acoustic conductance levels induced by positive and negative ear-canal static pressure. Study Sample: Twenty young adult subjects with normal hearing and a negative history of middle-ear disorders participated in the study. Data Collection and Analysis: Experimental pure-tone thresholds at 0.5 and 2.0 kHz were estimated by using a three-interval, three-alternative forced-choice adaptive psychometric procedure under three conditions: ambient ear-canal pressure, +200 daPa static pressure, and 200 daPa static pressure. Wideband absorbance and conductance were obtained in the same subjects by using a Welch Allyn prototype diagnostic middle ear analyzer. Changes in pure-tone threshold from the ambient pressure condition to the static pressure condition were evaluated by using a paired-samples t test and Pearson productmoment correlation. Results: Wideband middle-ear absorbance and conductance at ambient pressure in this study were consistent with published data in adults with normal hearing. The mean change in threshold at 0.5 and 2.0 kHz with +200 daPa or -200 daPa ear-canal static pressure was similar to the mean change in absorbance and conductance levels in the same conditions. However, there was one statistically significant difference between the shift in pure-tone threshold and the change in conductance level for the +200 daPa pressure condition for 2.0 kHz, with the change in threshold being 1.5 dB greater than the change in conductance level (t = 2.39, p = 0.03). In contrast to the good performance of WAI measures in predicting mean threshold shifts caused by ear-canal pressure, the shifts in WAI were not correlated with threshold shifts. Thus WAI was not well suited to predict individual threshold changes caused by ear-canal static pressure. Conclusions: For the conditions of this study, results suggest that mean change in absorbance or conductance level caused by ear-canal static pressure of +200 daPa or 200 daPa provides a good estimate of the change in pure-tone threshold in the same conditions. However, individual threshold change was not accurately predicted by the change in absorbance or conductance level. C1 [Feeney, M. Patrick; Putterman, Daniel B.] Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. [Feeney, M. Patrick; Putterman, Daniel B.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Feeney, M. Patrick] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Sanford, Chris A.] Idaho State Univ, Dept Commun Sci & Disorders, Pocatello, ID 83209 USA. RP Feeney, MP (reprint author), Portland VA Med Ctr, NCRAR, 3710 SW US Vet Hosp Rd,P5-NCRAR, Portland, OR 97239 USA. EM Patrick.Feeney@va.gov FU VA RRD award [C9230C] FX Support for the first and last authors was provided by VA RR&D award C9230C. The content of this article does not represent the views of the Department of Veterans Affairs or the United States Government. NR 29 TC 0 Z9 0 U1 1 U2 5 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD MAY PY 2014 VL 25 IS 5 SI SI BP 462 EP 470 DI 10.3766/jaaa.25.5.5 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AQ7RX UT WOS:000343018000005 PM 25257720 ER PT J AU Leder, BZ Tsai, JN Uihlein, AV Burnett-Bowie, SAM Zhu, Y Foley, K Lee, H Neer, RM AF Leder, Benjamin Z. Tsai, Joy N. Uihlein, Alexander V. Burnett-Bowie, Sherri-Ann M. Zhu, Yuli Foley, Katelyn Lee, Hang Neer, Robert M. TI Two Years of Denosumab and Teriparatide Administration in Postmenopausal Women With Osteoporosis (The DATA Extension Study): A Randomized Controlled Trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; PARATHYROID-HORMONE; ZOLEDRONIC ACID; FRACTURE RISK; ALENDRONATE; THERAPY; COMBINATION; REDUCTION; MEN AB Context: Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone. Objective: The purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent. Design: Preplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 mu g daily), denosumab (60 mg every 6 months), or both medications for 24 months. Participants: Participants were 94 postmenopausal women with osteoporosis. Outcome Measures: Lumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured. Results: At 24 months, lumbar spine BMD increased more in the combination group (12.9 +/- 5.0%) than in either the teriparatide (9.5 +/- 5.9%, P = .01) or denosumab (8.3 +/- 3.4%, P = .008) groups. Femoral neck BMD also increased more in the combination group (6.8 +/- 3.6%) than in either the teriparatide (2.8 +/- 3.9%, P = .003) or denosumab (4.1 +/- 3.8%, P = .008) groups. Similarly, total hip BMD increased more in the combination group (6.3 +/- 2.6%) than in the teriparatide (2.0 +/- 3.0%) or denosumab (3.2 +/- 2.5%) groups (P < .001 for both). Although spine and hip BMD continued to increase in the second year in all groups, these year 2 increases did not differ among groups. Serum C-telopeptide and N-terminal propeptide of type 1 procollagen were equally suppressed in the denosumab and combination groups, whereas osteocalcin decreased more in the denosumab group than in the combination group, a difference that persisted, but lessened, in the second year of therapy. Conclusions: Two years of concomitant teriparatide and denosumab therapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy. The combination of these agents may prove to be an important treatment option in patients at high risk of fracture. C1 [Leder, Benjamin Z.; Tsai, Joy N.; Uihlein, Alexander V.; Burnett-Bowie, Sherri-Ann M.; Zhu, Yuli; Foley, Katelyn; Neer, Robert M.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM bzleder@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU Eli Lilly Inc; Amgen Inc; Harvard Clinical and Translational Science Center; National Center for Research Resources [1 ULI RR025758-04] FX This work was supported by Eli Lilly Inc, Amgen Inc, and by the Harvard Clinical and Translational Science Center, the National Center for Research Resources (Grant 1 ULI RR025758-04). Neither Eli Lilly nor Amgen had any role in study design or data analysis or data interpretation. NR 23 TC 52 Z9 55 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1694 EP 1700 DI 10.1210/jc.2013-4440 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800052 PM 24517156 ER PT J AU El-Khatib, FH Russell, SJ Magyar, KL Sinha, M McKeon, K Nathan, DM Damiano, ER AF El-Khatib, Firas H. Russell, Steven J. Magyar, Kendra L. Sinha, Manasi McKeon, Katherine Nathan, David M. Damiano, Edward R. TI Autonomous and Continuous Adaptation of a Bihormonal Bionic Pancreas in Adults and Adolescents With Type 1 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXCHANGE CLINIC REGISTRY; LOOP INSULIN DELIVERY; LOGIC ARTIFICIAL PANCREAS; GLUCOSE CONTROL; SEVERE HYPOGLYCEMIA; YOUNG-ADULTS; SYSTEM; KETOACIDOSIS; FEASIBILITY; THERAPY AB Context: A challenge for automated glycemic control in type 1 diabetes (T1D) is the large variation in insulin needs between individuals and within individuals at different times in their lives. Objectives: The objectives of the study was to test the ability of a third-generation bihormonal bionic pancreas algorithm, initialized with only subject weight; to adapt automatically to the different insulin needs of adults and adolescents; and to evaluate the impact of optional, automatically adaptive meal-priming boluses. Design: This was a randomized controlled trial. Setting: The study was conducted at an inpatient clinical research center. Patients: Twelve adults and 12 adolescents with T1D participated in the study. Interventions: Subjects in each age group were randomized to automated glycemic control for 48 hours with or without automatically adaptive meal-priming boluses. Main Outcome Measures: Mean plasma glucose (PG), time with PG less than 60 mg/dL, and insulin total daily dose were measured. Results: The 48-hour mean PG values with and without adaptive meal-priming boluses were 132 +/- 9vs 146 +/- 9 mg/dL (P = .03) in adults and 162 +/- 6vs 175 +/- 9 mg/dL (P = .01) in adolescents. Adaptive meal-priming boluses improved mean PG without increasing time spent with PG less than 60 mg/dL: 1.4% vs 2.3% (P = .6) in adults and 0.1% vs 0.1% (P = 1.0) in adolescents. Large increases in adaptive meal-priming boluses and shifts in the timing and size of automatic insulin doses occurred in adolescents. Much less adaptation occurred in adults. There was nearly a 4-fold variation in the total daily insulin dose across all cohorts (0.36-1.41 U/kg.d). Conclusions: A single control algorithm, initialized only with subject weight, can quickly adapt to regulate glycemia in patients with TID and highly variable insulin requirements. C1 [El-Khatib, Firas H.; McKeon, Katherine; Damiano, Edward R.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Russell, Steven J.; Magyar, Kendra L.; Sinha, Manasi; Nathan, David M.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Russell, Steven J.; Magyar, Kendra L.; Sinha, Manasi; Nathan, David M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Russell, Steven J.; Magyar, Kendra L.; Sinha, Manasi; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Russell, SJ (reprint author), Massachusetts Gen Hosp, Diabet Res Ctr, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM sjrussell@partners.org FU National Institutes of Health Grant [R01-DK085633]; Leona M. and Harry B. Helmsley Charitable Trust [22-2010-771]; National Institutes of Health National Center for Research Resources through the General Clinical Research Center and Clinical and Translational Science Center programs [M01-RR01066, UL1-RR025758]; Charlton Fund for Innovative Research in Diabetes FX This study was supported by National Institutes of Health Grant R01-DK085633 (to E.R.D.); Juvenile Diabetes Research Foundation Grant 22-2010-771 (to E.R.D.) from The Leona M. and Harry B. Helmsley Charitable Trust; Grants M01-RR01066 and UL1-RR025758 from the National Institutes of Health National Center for Research Resources through the General Clinical Research Center and Clinical and Translational Science Center programs; and a grant from the Charlton Fund for Innovative Research in Diabetes (to D.M.N.). NR 47 TC 30 Z9 30 U1 0 U2 11 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1701 EP 1711 DI 10.1210/jc.2013-4151 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800053 PM 24483160 ER PT J AU Guillemette, L Lacroix, M Battista, MC Doyon, M Moreau, J Menard, J Ardilouze, JL Perron, P Hivert, MF AF Guillemette, Laetitia Lacroix, Marilyn Battista, Marie-Claude Doyon, Myriam Moreau, Julie Menard, Julie Ardilouze, Jean-Luc Perron, Patrice Hivert, Marie-France TI TNF alpha Dynamics During the Oral Glucose Tolerance Test Vary According to the Level of Insulin Resistance in Pregnant Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; GESTATIONAL DIABETES-MELLITUS; TISSUE IN-VITRO; ADIPOSE-TISSUE; OBESITY; SENSITIVITY; HYPERGLYCEMIA; ADIPONECTIN; RELEASE; CELLS AB Introduction: TNF alpha is suspected to play a role in inflammation and insulin resistance leading to higher risk of metabolic impairment. Controversies exist concerning the role of TNF alpha in gestational insulin resistance. Weinvestigated the interrelations between TNF alpha and insulin resistance in a large population-based cohort of pregnant women. Methods: Women (n = 756) were followed prospectively at 5-16 weeks and 24-28 weeks of pregnancy. Anthropometric measures and blood samples were collected at both visits. A 75-g oral glucose tolerance test (OGTT) was conducted at the second trimester to assess insulin sensitivity status (homeostasis model of assessment of insulin resistance and Matsuda index). TNF alpha was measured at the first trimester (nonfasting) and at each time point of the OGTT. Results: Participants were 28.4 +/- 4.4 years old and had a mean body mass index of 25.5 +/- 5.5 kg/m(2) at first trimester. Median TNF alpha levels were 1.56 (interquartile range, 1.18-2.06) pg/mL at first trimester and 1.61 (interquartile range, 1.12-2.13) pg/mL at second trimester (1 h after glucose load). At second trimester, higher TNF alpha levels were associated with higher insulin resistance index levels (r = 0.37 and -0.30 for homeostasis model of assessment of insulin resistance and Matsuda index, respectively; P < .0001), even after adjustment for age, body mass index, triglycerides, and adiponectin. Women with higher insulin resistance showed a continuing decrease in TNF alpha levels during the OGTT, whereas women who were more insulin sensitive showed an increase in TNF alpha at hour 1 and a decrease at hour 2 of the test. Conclusion: Higher insulin resistance is associated with higher levels of circulating TNF alpha at first and second trimesters of pregnancy. TNF alpha level dynamics during an OGTT at second trimester vary according to insulin-resistance state. C1 [Guillemette, Laetitia; Lacroix, Marilyn; Battista, Marie-Claude; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1H 5N4, Canada. [Doyon, Myriam; Moreau, Julie; Menard, Julie; Ardilouze, Jean-Luc; Hivert, Marie-France] CHU Sherbrooke, Ctr Rech Clin Eetienne Le Bel, Sherbrooke, PQ J1H 5N4, Canada. [Hivert, Marie-France] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02215 USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, 133 Brook Line Ave,Sixth Floor, Boston, MA 02215 USA. EM marie-france_hivert@harvardpilgrim.org FU Fonds de la recherche du Quebec en sante (FRQ-S); Diabete Quebec internship award; FRQ-S Master's training award; Diabete Quebec grant; Canadian Diabetes Association operating grant; Canadian Diabetes Association; Institute of Genetics-Canadian Institute of Health Research FX The study was supported by a Fonds de la recherche du Quebec en sante (FRQ-S) operating grant (to M.-F.H.), a Diabete Quebec internship award and a FRQ-S Master's training award (to L.G.); by a Diabete Quebec grant (to P.P.); and by a Canadian Diabetes Association operating grant (to J.-L.A.). M.-F.H. is an FRQ-S research scholar and was awarded a Clinical Scientist Award by the Canadian Diabetes Association and the Maud Menten Award from the Institute of Genetics-Canadian Institute of Health Research. J.-L.A. is a FRQ-S junior 2 research scholar. Clinical assessments were performed at the Clinical Research Center Etienne-Le Bel (CRCELB) affiliated with the CHUS; the CRCELB is an FRQ-S-supported research center. No potential conflicts of interest relevant to this article were reported. NR 41 TC 10 Z9 10 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1862 EP 1869 DI 10.1210/jc.2013-4016 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800071 PM 24517151 ER PT J AU Pau, CT Keefe, C Duran, J Welt, CK AF Pau, Cindy T. Keefe, Candace Duran, Jessica Welt, Corrine K. TI Metformin Improves Glucose Effectiveness, Not Insulin Sensitivity: Predicting Treatment Response in Women With Polycystic Ovary Syndrome in an Open-Label, Interventional Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; DIABETES-MELLITUS; RESPIRATORY-CHAIN; SKELETAL-MUSCLE; ANDROGEN PRODUCTION; METABOLIC SYNDROME; NONOBESE WOMEN; TOLERANCE TEST; DOUBLE-BLIND; COMPLEX I AB Context: Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response. Objective: The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment. Design and Setting: We conducted an open-label, interventional study at an academic medical center. Subjects: Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study. Interventions: Subjects underwent fasting blood sampling, an IV glucose tolerance test, dual-energy x-ray absorptiometry scan, transvaginal ultrasound, and measurement of human chorionic gonadotropin-stimulated androgen levels before and after 12 weeks of treatment with metformin extended release 1500 mg/d. Interval visits were performed to monitor anthropometric measurements and menstrual cycle parameters. Main Outcome Measures: Changes in glucose and insulin parameters, androgen levels, anthropometric measurements, and ovulatory menstrual cycles were evaluated. Results: Insulin sensitivity did not change despite weight loss. Glucose effectiveness (P = .002) and the acute insulin response to glucose (P = .002) increased, and basal glucose levels (P = .001) decreased after metformin treatment. T levels also decreased. Women with improved ovulatory function (61%) had lower baseline T levels and lower baseline and stimulated T and androstenedione levels after metformin treatment (all P < .05). Conclusions: Using an IV glucose tolerance test, which distinguishes improvements in glucose effectiveness and insulin sensitivity, metformin does not improve insulin sensitivity in women with PCOS but does improve glucose effectiveness. The improvement in glucose effectiveness may be partially mediated by decreased glucose levels. T levels also decreased with metformin treatment. Ovulation during metformin treatment was associated with lower baseline T levels and greater T and androstenedione decreases during treatment, but not with insulin or LH levels. Thus, the action of metformin in PCOS primarily affects glucose levels and steroidogenesis, which may be mediated by mechanisms that affect both pathways, such as inhibition of mitochondrial complex I. C1 [Pau, Cindy T.; Keefe, Candace; Duran, Jessica; Welt, Corrine K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU American Diabetes Association [1-10-CT-57]; National Institutes of Health [1R01HD065029, 1 UL1 RR025758] FX This work was supported by American Diabetes Association Grant 1-10-CT-57 (to C.K.W.), and National Institutes of Health Grants 1R01HD065029 (to C.K.W.), and 1 UL1 RR025758 (to the Harvard Clinical and Translational Science Center). NR 56 TC 17 Z9 17 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP 1870 EP 1878 DI 10.1210/jc.2013-4021 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800072 PM 24606093 ER PT J AU Billings, LK Jablonski, KA Ackerman, RJ Taylor, A Fanelli, RR McAteer, JB Guiducci, C Delahanty, LM Dabelea, D Kahn, SE Franks, PW Hanson, RL Maruthur, NM Shuldiner, AR Mayer-Davis, EJ Knowler, WC Florez, JC AF Billings, Liana K. Jablonski, Kathleen A. Ackerman, Rachel J. Taylor, Andrew Fanelli, Rebecca R. McAteer, Jarred B. Guiducci, Candace Delahanty, Linda M. Dabelea, Dana Kahn, Steven E. Franks, Paul W. Hanson, Robert L. Maruthur, Nisa M. Shuldiner, Alan R. Mayer-Davis, Elizabeth J. Knowler, William C. Florez, Jose C. CA Diab Prevention Program Res Grp TI The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and beta-Cell Function SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZINC TRANSPORTER ZNT8; PREVENTION PROGRAM; INSULIN-SECRETION; LIFE-STYLE; BASE-LINE; GLUCOSE; ASSOCIATION; INTERVENTION; METFORMIN; VARIANTS AB Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate. Results: We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence. Conclusions: Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of beta-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases. C1 [Billings, Liana K.; Ackerman, Rachel J.; Taylor, Andrew; Fanelli, Rebecca R.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Billings, Liana K.] NorthShore Univ HealthSyst, Dept Med, Evanston, IL 60201 USA. [Billings, Liana K.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Taylor, Andrew; McAteer, Jarred B.; Guiducci, Candace; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Dabelea, Dana] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO 80045 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. [Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, SE-20041 Malmo, Sweden. [Hanson, Robert L.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. [Maruthur, Nisa M.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Dept Med, Baltimore, MD 21205 USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA. [Mayer-Davis, Elizabeth J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Simches Res Bldg CPZN 5-250, Boston, MA 02114 USA. EM dppmail@biostat.bsc.gwu.edu FU National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK072041]; NIH/NIDDK at the DPP Data Coordinating Center in George Washington University [U01 DK048489]; NIH Office of Dietary Supplements; NRSA Institutional Training Grant [T32 DK007028-35]; Endocrine Society's Lilly Scholar's Award; NIH Loan Repayment Award; NIDDK [1 L30 DK089944-01]; Doris Duke Charitable Foundation; NorthShore Auxiliary Research Scholar Award; Department of Veterans Affairs; NIDDK of the NIH; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association FX This work was supported by National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant R01 DK072041 to J.C.F., K.A.J., and A.R.S. and a subcontract from NIH/NIDDK U01 DK048489 at the DPP Data Coordinating Center in George Washington University to J.C.F., facilitated by a targeted grant from the NIH Office of Dietary Supplements. During the course of this study, L.K.B. was supported by NRSA Institutional Training Grant T32 DK007028-35 to the Massachusetts General Hospital, the Endocrine Society's Lilly Scholar's Award, NIH Loan Repayment Award, NIDDK 1 L30 DK089944-01, Harvard Catalyst, a Distinguished Clinical Scientist Award to David Altshuler from the Doris Duke Charitable Foundation, and the NorthShore Auxiliary Research Scholar Award. S.E.K. is supported in part by the Department of Veterans Affairs.; The NIDDK of the NIH provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, the Department of Veterans Affairs, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc, Health O Meter, Hoechst Marion Roussel, Inc, Merck-Medco Managed Care, Inc, Merck and Co, Nike Sports Marketing, Slim Fast Foods Co, and Quaker Oats Co donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp, Matthews Media Group, Inc, and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centers, investigators, and staff can be found in the Supplemental Appendix. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP E926 EP E930 DI 10.1210/jc.2013-2378 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800025 PM 24471563 ER PT J AU Lawson, EA Ackerman, KE Slattery, M Marengi, DA Clarke, H Misra, M AF Lawson, Elizabeth A. Ackerman, Kathryn E. Slattery, Meghan Marengi, Dean A. Clarke, Hannah Misra, Madhusmita TI Oxytocin Secretion Is Related to Measures of Energy Homeostasis in Young Amenorrheic Athletes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE MICROARCHITECTURE; DEFICIENT MICE; PGC-1-ALPHA; OBESITY; RAT; FAT AB Context: Oxytocin has been implicated in the modulation of energy metabolism in animals. Oxytocin knockout mice develop obesity without a change in food intake, suggesting that a lack of oxytocin may reduce metabolic rate. Furthermore, administration of oxytocin centrally reduces food intake in rats, an effect reversed by an oxytocin antagonist, implying that oxytocin may regulate appetite and energy intake. We have previously demonstrated that young female athletes (in a higher energy expenditure state than nonathletes) have low nocturnal oxytocin compared with nonathletes. Whether oxytocin is associated with measures of energy homeostasis in athletes is unknown. Objective: We hypothesized that oxytocin, a signal for energy availability, would be associated with other measures of energy homeostasis in young female athletes. Design and Setting: We performed a cross-sectional study of 45 females, aged 14-21 years [15 amenorrheic athletes (AA), 15 eumenorrheic athletes, and 15 nonathletes] of comparable body mass index. Methods: Dual x-ray absorptiometry was performed to assess body composition. Indirect calorimetry was used to measure resting energy expenditure (REE). Fasting levels of oxytocin, energy homeostasis hormones irisin and fibroblast growth factor-21, and appetite-regulating hormone peptide YY were obtained. Results: In AA, oxytocin secretion was positively correlated with surrogate measures of energy availability, including weight (r = 0.65, P = .009) and body mass index (r = 0.61, P = .016). Furthermore, oxytocin was associated with REE (r = 0.80, P = .0003), independent of lean mass, and with irisin (r = 0.74, P = .002) and fibroblast growth factor-21 (r = 0.58, P = .024). In eumenorrheic athletes, oxytocin was associated with REE (r = 0.59, P = .021), independent of lean mass. In nonathletes, oxytocin secretion was not significantly associated with measures of energy homeostasis. Conclusions: In AA, oxytocin secretion is associated with measures of energy availability and expenditure, suggesting that oxytocin may be involved in regulation of energy balance in energy deficient states. Further studies determining the role of oxytocin in appetite and energy homeostasis in athletes are warranted. C1 [Lawson, Elizabeth A.; Ackerman, Kathryn E.; Slattery, Meghan; Marengi, Dean A.; Clarke, Hannah; Misra, Madhusmita] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Dept Orthoped, Div Sports Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02116 USA. EM ealawson@partners.org FU National Institutes of Health [UL1 RR025758, RO1 HD060827, K23 MH092560, K24 HD071843]; Massachusetts General Hospital Claflin Distinguished Scholar Award FX This work was supported by National Institutes of Health Grants UL1 RR025758, RO1 HD060827, K23 MH092560, and K24 HD071843 and by Massachusetts General Hospital Claflin Distinguished Scholar Award. NR 20 TC 5 Z9 6 U1 3 U2 9 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2014 VL 99 IS 5 BP E881 EP E885 DI 10.1210/jc.2013-4136 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PB UT WOS:000342339800019 PM 24606095 ER PT J AU Unizony, S AF Unizony, Sebastian TI MECHANISTIC AND IMAGING SUBSTUDIES IN GIACTA SO RHEUMATOLOGY LA English DT Meeting Abstract CT 2nd International Symposium and Imaging Workshop on Giant Cell Arteritis, Polymyalgia Rheumatica and Large Vessel Vasculitis CY NOV 22-24, 2013 CL Southend, ENGLAND ID GIANT-CELL ARTERITIS; REGULATORY T-CELLS; TH17; RESPONSES; IMMUNITY C1 [Unizony, Sebastian] Massachusetts Gen Hosp, Rheumatol Allergy & Immunol Div, Boston, MA 02114 USA. [Unizony, Sebastian] Harvard Univ, Sch Med, Boston, MA USA. EM sunizony@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD MAY PY 2014 VL 53 SU 2 MA 10 BP 6 EP 6 PG 1 WC Rheumatology SC Rheumatology GA AP8TD UT WOS:000342350900011 ER PT J AU Rampersad, SM Janssen, AM Lucka, F Aydin, U Lanfer, B Lew, S Wolters, CH Stegeman, DF Oostendorp, TF AF Rampersad, Sumientra M. Janssen, Arno M. Lucka, Felix Aydin, Uemit Lanfer, Benjamin Lew, Seok Wolters, Carsten H. Stegeman, Dick F. Oostendorp, Thom F. TI Simulating Transcranial Direct Current Stimulation With a Detailed Anisotropic Human Head Model SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Cerebellum; finite element model (FEM); motor cortex; occipital cortex; prefrontal cortex; transcranial direct current stimulation (tDCS) ID DORSOLATERAL PREFRONTAL CORTEX; NONINVASIVE CORTICAL STIMULATION; HUMAN MOTOR CORTEX; DIELECTRIC-PROPERTIES; MAGNETIC STIMULATION; BIOLOGICAL TISSUES; ELECTRIC-FIELD; WHITE-MATTER; TDCS; EXCITABILITY AB Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce long-lasting changes in cortical excitability that can benefit cognitive functioning and clinical treatment. In order to both better understand the mechanisms behind tDCS and possibly improve the technique, finite element models are used to simulate tDCS of the human brain. With the detailed anisotropic head model presented in this study, we provide accurate predictions of tDCS in the human brain for six of the practically most-used setups in clinical and cognitive research, targeting the primary motor cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, occipital cortex, and cerebellum. We present the resulting electric field strengths in the complete brain and introduce new methods to evaluate the effectivity in the target area specifically, where we have analyzed both the strength and direction of the field. For all cerebral targets studied, the currently accepted configurations produced sub-optimal field strengths. The configuration for cerebellum stimulation produced relatively high field strengths in its target area, but it needs higher input currents than cerebral stimulation does. This study suggests that improvements in the effects of transcranial direct current stimulation are achievable. C1 [Rampersad, Sumientra M.; Janssen, Arno M.; Stegeman, Dick F.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 HB Nijmegen, Netherlands. [Rampersad, Sumientra M.; Janssen, Arno M.; Stegeman, Dick F.; Oostendorp, Thom F.] Donders Inst Brain Cognit & Behav, NL-6525 EZ Nijmegen, Netherlands. [Lucka, Felix; Aydin, Uemit; Lanfer, Benjamin; Wolters, Carsten H.] Univ Munster, Inst Biomagnetism & Biosignalanal, D-48149 Munster, Germany. [Lucka, Felix] Univ Munster, Inst Computat & Appl Math, D-48149 Munster, Germany. [Lanfer, Benjamin] BESA GmbH, D-82166 Grafelfing, Germany. [Lew, Seok] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Stegeman, Dick F.] Vrije Univ Amsterdam, Fac Human Movement Sci, NL-1081 BT Amsterdam, Netherlands. [Stegeman, Dick F.] Vrije Univ Amsterdam, MOVE Res Inst, NL-1081 BT Amsterdam, Netherlands. [Oostendorp, Thom F.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands. RP Rampersad, SM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 HB Nijmegen, Netherlands. EM dick.stegeman@radboudumc.nl RI Wolters, Carsten/R-4234-2016 OI Wolters, Carsten/0000-0001-6233-424X FU BrainGain Smart Mix Programme of the Netherlands Ministry of Economic Affairs; Netherlands Ministry of Education, Culture and Science; German Research Foundation [DFG WO1425/2-1, SPP1665, WO1425/5-1]; BESA GmbH, Grafelfing, Germany; German National Academic Foundation (Studienstiftung des deutschen Volkes); NIH (NIH) [R01EB0009048]; National Center for Research Resources [5P41RR012553-15]; National Institute of General Medical Sciences from the National Institutes of Health [8 P41 GM103545-15] FX This work was supported by the BrainGain Smart Mix Programme of the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science. The work of C. Wolters was supported by the German Research Foundation (DFG WO1425/2-1 and by the priority program SPP1665, project WO1425/5-1) for U. Aydin and from BESA GmbH, Grafelfing, Germany for B. Lanfer. The work of F. Lucka was supported by the German National Academic Foundation (Studienstiftung des deutschen Volkes). The work of S. Lew was supported by NIH (NIH Grant R01EB0009048). The study was made possible in part by software that is developed with the support of grants from the National Center for Research Resources (5P41RR012553-15) and the National Institute of General Medical Sciences (8 P41 GM103545-15) from the National Institutes of Health. NR 62 TC 30 Z9 30 U1 0 U2 14 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD MAY PY 2014 VL 22 IS 3 BP 441 EP 452 DI 10.1109/TNSRE.2014.2308997 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA AP4WE UT WOS:000342079300002 PM 24760939 ER PT J AU Agrawal, MD Pinho, DF Kulkarni, NM Hahn, PF Guimaraes, AR Sahani, DV AF Agrawal, Mukta D. Pinho, Daniella F. Kulkarni, Naveen M. Hahn, Peter F. Guimaraes, Alexander R. Sahani, Dushyant V. TI Oncologic Applications of Dual-Energy CT in the Abdomen SO RADIOGRAPHICS LA English DT Article ID LOW-TUBE-VOLTAGE; HYPERVASCULAR LIVER-TUMORS; IODINE OVERLAY TECHNIQUE; RENAL MASSES; IMAGE QUALITY; COMPUTED-TOMOGRAPHY; INITIAL-EXPERIENCE; MULTIDETECTOR CT; FATTY LIVER; CONTRAST AB Dual-energy computed tomographic (DECT) technology offers enhanced capabilities that may benefit oncologic imaging in the abdomen. By using two different energies, dual-energy CT allows material decomposition on the basis of energy-dependent attenuation profiles of specific materials. Although image acquisition with dual-energy CT is similar to that with single-energy CT, comprehensive postprocessing is able to generate not only images that are similar to single-energy CT (SECT) images, but a variety of other images, such as virtual unenhanced (VUE), virtual monochromatic (VMC), and material-specific iodine images. An increase in the conspicuity of iodine on low-energy VMC images and material-specific iodine images may aid detection and characterization of tumors. Use of VMC images of a desired energy level (40-140 keV) improves lesion-to-background contrast and the quality of vascular imaging for preoperative planning. Material-specific iodine images enable differentiation of hypoattenuating tumors from hypo-or hyperattenuating cysts and facilitate detection of isoattenuating tumors, such as pancreatic masses and peritoneal disease, thereby defining tumor targets for imaging-guided therapy. Moreover, quantitative iodine mapping may serve as a surrogate biomarker for monitoring effects of the treatment. Dual-energy CT is an innovative imaging technique that enhances the capabilities of CT in evaluating oncology patients. (C) RSNA 2014 C1 [Agrawal, Mukta D.; Pinho, Daniella F.; Kulkarni, Naveen M.; Hahn, Peter F.; Guimaraes, Alexander R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Abdominal & Intervent Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal & Intervent Radiol, 55 Fruit St,White Bldg,Room 270, Boston, MA 02114 USA. EM dsahani@partners.org FU GE Healthcare; Siemens Medical Systems FX received grants from GE Healthcare and Siemens Medical Systems and royalties from Elsevier. NR 53 TC 24 Z9 33 U1 3 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2014 VL 34 IS 3 BP 589 EP 612 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AP2PH UT WOS:000341915200006 PM 24819783 ER PT J AU Shaaban, AM Rezvani, M Elsayes, KM Baskin, H Mourad, A Foster, BR Jarboe, EA Menias, CO AF Shaaban, Akram M. Rezvani, Maryam Elsayes, Khaled M. Baskin, Henry, Jr. Mourad, Amr Foster, Bryan R. Jarboe, Elke A. Menias, Christine O. TI Ovarian Malignant Germ Cell Tumors: Cellular Classification and Clinical and Imaging Features SO RADIOGRAPHICS LA English DT Article ID MATURE CYSTIC TERATOMA; ENDODERMAL SINUS TUMOR; PSEUDO-MEIGS-SYNDROME; STRUMA OVARII; PATHOLOGICAL CORRELATION; CARCINOID-TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS; PREOPERATIVE DIAGNOSIS; IMMATURE TERATOMAS AB Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient's age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care. (C)RSNA, 2014. C1 [Shaaban, Akram M.; Rezvani, Maryam] Univ Utah, Dept Diagnost Radiol, Salt Lake City, UT 84132 USA. [Baskin, Henry, Jr.] Univ Utah, Dept Radiol, Primary Childrens Med Ctr, Salt Lake City, UT 84132 USA. [Elsayes, Khaled M.] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Mourad, Amr] VA Pittsburgh Healthcare Syst, Dept Diagnost Radiol, Pittsburgh, PA USA. [Foster, Bryan R.] Oregon Hlth & Sci Univ, Dept Diagnost Radiol, Portland, OR 97201 USA. [Jarboe, Elke A.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. [Menias, Christine O.] Mayo Clin, Dept Radiol, Scottsdale, AZ USA. RP Shaaban, AM (reprint author), Univ Utah, Dept Diagnost Radiol, 30 N 1900 E,Room 1A71, Salt Lake City, UT 84132 USA. EM akram.shaaban@hsc.utah.edu NR 84 TC 7 Z9 9 U1 3 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2014 VL 34 IS 3 BP 777 EP 801 DI 10.1148/rg.343130067 PG 25 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AP2PH UT WOS:000341915200018 PM 24819795 ER PT J AU Cai, WL Lee, JG Yoshida, H Kim, SH AF Cai, Wenli Lee, June-Goo Yoshida, Hiroyuki Kim, Se Hyung TI Dual-Energy CT for Diagnostic CT Colonography Response SO RADIOGRAPHICS LA English DT Letter ID COMPUTED-TOMOGRAPHY C1 [Cai, Wenli; Lee, June-Goo; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Lee, June-Goo; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Se Hyung] Seoul Natl Univ Hosp, Coll Med, Dept Radiol, Seoul 110744, South Korea. 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 2 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2014 VL 34 IS 3 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AP2PH UT WOS:000341915200024 ER PT J AU Lutwak, N Byne, W Erickson-Schroth, L Keig, Z Shipherd, JC Mattocks, KM Kauth, MR AF Lutwak, Nancy Byne, William Erickson-Schroth, Laura Keig, Zander Shipherd, Jillian C. Mattocks, Kristin M. Kauth, Michael R. TI Transgender Veterans Are Inadequately Understood by Health Care Providers SO MILITARY MEDICINE LA English DT Editorial Material ID MENTAL-HEALTH; STIGMA; GAY; POPULATION; PROMOTION; ILLNESS C1 [Lutwak, Nancy] NYU, Sch Med, New York Harbor Healthcare Syst, Dept Emergency Med, New York, NY 10010 USA. [Byne, William] Res Educ & Clin Ctr, Vet Integrated Serv Network Mental Illness 3, James J Peters VA Med Ctr, New York, NY 10468 USA. [Byne, William] Mt Sinai Hosp, Icahn Sch Med, Dept Psychiat, New York, NY 10468 USA. [Erickson-Schroth, Laura] NYU, Med Ctr, Dept Psychiat, New York, NY 10016 USA. [Keig, Zander] VA Northern Calif Hlth Care Syst, Oakland Behav Hlth Clin, Oakland, CA 94612 USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Jamaica Plain, MA 02130 USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Jamaica Plain, MA 02130 USA. [Shipherd, Jillian C.] VA Patient Care Serv, Lesbian Gay Bisexual & Transgender Program, Washington, DC USA. [Mattocks, Kristin M.] VA Cent Western Massachusetts Healthcare Syst, Leeds, MA 01053 USA. [Mattocks, Kristin M.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci Psychiat, Leeds, MA 01053 USA. [Kauth, Michael R.] Michael E DeBakey VA Med Ctr, Educ & Clin Ctr, South Cent Mental Illness Res, Houston, TX 77030 USA. [Kauth, Michael R.] Baylor Coll Med, VA Hlth Serv Res & Dev, Houston Ctr Excellence, Houston, TX 77030 USA. RP Lutwak, N (reprint author), NYU, Sch Med, New York Harbor Healthcare Syst, Dept Emergency Med, 423 East 23rd St, New York, NY 10010 USA. NR 36 TC 2 Z9 2 U1 2 U2 8 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD MAY PY 2014 VL 179 IS 5 BP 483 EP 485 DI 10.7205/MILMED-D-14-00001 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AN7UL UT WOS:000340806400005 PM 24806492 ER PT J AU Chen, LLK Baca, CB Choe, J Chen, JW Ayad, ME Cheng, EM AF Chen, Leo L. K. Baca, Christine B. Choe, Jessica Chen, James W. Ayad, Miriam E. Cheng, Eric M. TI Posttraumatic Epilepsy in Operation Enduring Freedom/Operation Iraqi Freedom Veterans SO MILITARY MEDICINE LA English DT Article ID TRAUMATIC BRAIN-INJURY; EMOTIONAL RISK-FACTORS; HEAD-INJURY; NONEPILEPTIC SEIZURES; CODES; ASCERTAINMENT; DIAGNOSIS; ACCURACY; DISORDER; VALIDITY AB Penetrating traumatic brain injury (TBI) is a well-established risk factor for post-traumatic epilepsy (PTE). However, many veterans in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) who suffer from TBI do so from blast injury, and its consequences are not fully known. Two neurologists performed a chart review to describe patterns of injury and health care among all 16 OEF/OIF veterans at the VA Greater Los Angeles Healthcare System who were assigned an outpatient diagnosis of both epilepsy and TBI in 2008-2009. All Veterans were male, and the mean age was 30 years. Blast exposure was the most common mechanism of TBI (81%). Although all Veterans were assigned a diagnosis code of seizures, the diagnosis of PTE was clinically confirmed in only 3 veterans. On the other hand, the diagnosis of post-traumatic stress disorder was confirmed in 81% of the sample and a diagnosis of nonepileptic seizures was suspected in 44% of the sample. Researchers who study PTE among the OEF/OIF population using administrative data also should perform chart reviews to account for the prevalence of psychogenic nonepileptic seizures. C1 [Chen, Leo L. K.] Kaiser Permanente Fdn Hosp, Dept Neurol, Sacramento, CA 95825 USA. [Chen, Leo L. K.] UC Davis Hlth Syst, Dept Neurol, Sacramento, CA 95817 USA. [Baca, Christine B.; Choe, Jessica] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. [Baca, Christine B.; Choe, Jessica; Chen, James W.; Ayad, Miriam E.; Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. [Chen, James W.; Ayad, Miriam E.; Cheng, Eric M.] UCLA, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Chen, LLK (reprint author), Kaiser Permanente Fdn Hosp, Dept Neurol, 2025 Morse Ave, Sacramento, CA 95825 USA. FU VA Epilepsy Center of Excellence at VA Los Angeles; NIH/NINDS [K23NS058571] FX The study was supported by the VA Epilepsy Center of Excellence at VA Los Angeles. Dr. Cheng was supported by Career Development Award from NIH/NINDS (K23NS058571). NR 28 TC 4 Z9 4 U1 1 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD MAY PY 2014 VL 179 IS 5 BP 492 EP 496 DI 10.7205/MILMED-D-13-00413 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AN7UL UT WOS:000340806400007 PM 24806494 ER PT J AU Donean, K Romano, C DesRoches, C Applebaum, S Ward, JRM Schoneboom, BA Hinshaw, AS AF Donean, Karen Romano, Carol DesRoches, Catherine Applebaum, Sandra Ward, Johanna R. M. Schoneboom, Bruce A. Hinshaw, Ada Sue TI National Surveys of Military Personnel, Nursing Students, and the Public: Drivers of Military Nursing Careers SO MILITARY MEDICINE LA English DT Article ID NURSES AB Objectives: The U.S. health care system is facing a projected nursing shortage of unprecedented magnitude. Although military nursing services recently have been able to meet their nursing recruitment quotas, national studies have predicted a long-term nursing shortage that may affect future recruitment for the Nurse Corps of the three military services. Data are needed to plan for recruitment incentives and the impact of those incentives on targeted populations of likely future nurses. Methods: Data are drawn from three online surveys conducted in 2011-2012, including surveys of 1,302 Army, Navy, and Air Force personnel serving on major military bases, 914 nursing students at colleges with entry Bachelor of Science in Nursing programs located nearby major military bases, and a qualitative survey of 1,200 young adults, age 18-39, in the general public. Findings: The three populations are different in several demographic characteristics. We explored perceptions of military careers, nursing careers and barriers, and incentives to pursue military nursing careers in all populations. Perceptions differ among the groups. Conclusion: The results of this study may help to inform strategies for reaching out to specific populations with targeted messages that focus on barriers and facilitators relevant to each to successfully recruit a diverse Nurse Corps for the future. C1 [Donean, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Romano, Carol; Hinshaw, Ada Sue] Uniformed Serv Univ Hlth Sci, Grad Sch Nursing, Bethesda, MD 20814 USA. [DesRoches, Catherine] Math Policy Res, Cambridge, MA 02139 USA. [Applebaum, Sandra] Harris Interact Inc, New York, NY 10010 USA. [Ward, Johanna R. M.] Math Policy Res, Princeton, NJ 08543 USA. [Schoneboom, Bruce A.] US Army, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. RP Donean, K (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th floor, Boston, MA 02114 USA. FU Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc [HU0001-05-D-0005, 0051] FX Funding for this project is from the Department of Defense's TRICARE Management Activity through a subcontract to Massachusetts General Hospital from The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc HU0001-05-D-0005 Task Order 0051. NR 15 TC 2 Z9 2 U1 0 U2 4 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD MAY PY 2014 VL 179 IS 5 BP 565 EP 572 DI 10.7205/MILMED-D-13-00323 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AN7UL UT WOS:000340806400016 PM 24806503 ER PT J AU Brown, J Shreay, S Rai, K AF Brown, J. Shreay, S. Rai, K. TI REAL WORLD TREATMENT PATTERNS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS IN THE UNITED STATES - RITUXIMAB, THE MOST COMMONLY USED AGENT SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Brown, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shreay, S.] Gilead Sci Inc, Foster City, CA 94404 USA. [Rai, K.] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PSY65 BP A235 EP A235 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001417 ER PT J AU Fonda, JR McGlinchey, RE Rudolph, JL Milberg, WP Hunt, PR Yonan, C Reynolds, MW AF Fonda, J. R. McGlinchey, R. E. Rudolph, J. L. Milberg, W. P. Hunt, P. R. Yonan, C. Reynolds, M. W. TI SCREENING FOR PBA SYMPTOMS USING A SINGLE QUESTION VERSUS A 7 QUESTION MEASURE AND ASSESSMENT OF THE ASSOCIATION OF PBA SYMPTOMS WITH HRQOL BURDEN SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Fonda, J. R.] VA Boston Healthcare Syst, Boston, MA USA. [McGlinchey, R. E.; Milberg, W. P.] Harvard Univ, Sch Med, Boston, MA USA. [Rudolph, J. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hunt, P. R.] Evidera, Lexington, MA USA. [Yonan, C.] Avanir Pharmaceut Inc, Aliso Viejo, CA USA. [Reynolds, M. W.] Evidera, Bethesda, MD USA. RI McGlinchey, Regina/R-1971-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PND45 BP A64 EP A64 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082000347 ER PT J AU Leinwand, B Brown, J Rai, K Inocencio, TJ Agatep, B AF Leinwand, B. Brown, J. Rai, K. Inocencio, T. J. Agatep, B. TI THE ECONOMIC AND HUMANISTIC BURDEN OF RELAPSED/REFRACTORY (R/R) INDOLENT NON-INDOLENT NON-HODGKIN'S LYMPHOMA (INHL): AN EVIDENCE GAP ANALYSIS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Leinwand, B.; Inocencio, T. J.; Agatep, B.] AVALERE HLTH LLC, Washington, DC USA. [Brown, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rai, K.] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PSY74 BP A236 EP A236 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001426 ER PT J AU Lo-Ciganic, W Donohue, JM Thorpe, CT Thorpe, JM Perera, S Marcum, ZA Gellad, WF AF Lo-Ciganic, W. Donohue, J. M. Thorpe, C. T. Thorpe, J. M. Perera, S. Marcum, Z. A. Gellad, W. F. TI EXAMINING A THRESHOLD OF ADHERENCE TO ORAL HYPOGLYCEMIC AGENTS RELEVANT TO CLINICAL OUTCOMES IN DIABETES: A TREE-STRUCTURED SURVIVAL MODEL SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Lo-Ciganic, W.; Donohue, J. M.; Perera, S.; Marcum, Z. A.; Gellad, W. F.] Univ Pittsburgh, Pittsburgh, PA USA. [Thorpe, C. T.; Thorpe, J. M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, W. F.] RAND, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PDB88 BP A253 EP A253 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001519 ER PT J AU Cerulli, C Kothari, CL Dichter, M Marcus, S Wiley, J Rhodes, KV AF Cerulli, Catherine Kothari, Catherine L. Dichter, Melissa Marcus, Steve Wiley, James Rhodes, Karin V. TI Victim Participation in Intimate Partner Violence Prosecution: Implications for Safety SO VIOLENCE AGAINST WOMEN LA English DT Article DE intimate partner violence; prosecution; safety ID DOMESTIC VIOLENCE; PROTECTION ORDERS; DECISION-MAKING; HEALTH-CARE; WOMEN; BARRIERS; ARREST; LEGAL; RISK; INTERVENTION AB Are intimate partner violence (IPV) victims safer if they use the criminal justice system? Concerns about perpetrator retaliation, in the face of data that protection orders can reduce future harm, make it important to understand how victim utilization (calling 911, talking to the prosecutor, and proceeding with prosecution) affects subsequent safety. We hypothesized participation would improve victims' safety, measured by decreases in subsequent IPV-related 911 calls and/or emergency department visits. Findings support contact with the prosecutor's office was associated with reduction in police-reported IPV, regardless of the victim's wish to proceed. Policy implications support pro-prosecution strategies coupled with victim contact. C1 [Cerulli, Catherine] Univ Rochester, Rochester, NY 14642 USA. [Kothari, Catherine L.] Western Michigan Univ, Kalamazoo, MI 49008 USA. [Dichter, Melissa; Marcus, Steve] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Marcus, Steve] Univ Penn, Philadelphia, PA 19104 USA. [Rhodes, Karin V.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Wiley, James] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Cerulli, C (reprint author), Univ Rochester, Sch Med & Dent, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM Catherine_Cerulli@urmc.rochester.edu NR 56 TC 2 Z9 2 U1 6 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 EI 1552-8448 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD MAY PY 2014 VL 20 IS 5 BP 539 EP 560 DI 10.1177/1077801214535105 PG 22 WC Women's Studies SC Women's Studies GA AN8VC UT WOS:000340882200005 PM 24894959 ER PT J AU Corbelli, J Borrero, S Bonnema, R McNamara, M Kraemer, K Rubio, D Karpov, I McNeil, M AF Corbelli, Jennifer Borrero, Sonya Bonnema, Rachel McNamara, Megan Kraemer, Kevin Rubio, Doris Karpov, Irina McNeil, Melissa TI Physician Adherence to US Preventive Services Task Force Mammography Guidelines SO WOMENS HEALTH ISSUES LA English DT Article ID PRIMARY-CARE PHYSICIANS; BREAST-CANCER RISK; HEART-FAILURE; RECOMMENDATIONS; METAANALYSIS; MALPRACTICE; MANAGEMENT; ATTITUDES; SUPPORT; SYSTEMS AB Background: In 2009, the U.S. Preventive Services Task Force (USPSTF) guidelines for screening mammography changed significantly, and are now in direct conflict with screening guidelines of other major national organizations. The extent to which physicians in different primary care specialties adhere to current USPSTF guidelines is unknown. Methods: We conducted a cross-sectional web-based survey completed by 316 physicians in internal medicine, family medicine (FM), and gynecology (GYN) from February to April 2012. Survey items assessed respondents' breast cancer screening recommendations in women of different ages at average risk for breast cancer. We used descriptive statistics to generate response distribution for survey items, and logistic regression models to compare responses among specialties. Findings: The response rate was 55.0% (316/575). A majority of providers in internal medicine (65%), FM (64%), and GYN (92%) recommended breast cancer screening starting at age 40 versus 50. A majority of providers in internal medicine (77%), FM (74%), and GYN (98%) recommended annual versus biennial screening. Gynecologists were significantly more likely than both internists and family physicians to recommend initial mammography at age 40 (p <= .0001) and yearly mammography (p = .0003). There were no other differences by respondent demographic. Conclusions: Primary care providers, especially gynecologists, have not implemented USPSTF guidelines. The extent to which these findings may be driven by patient versus provider preferences should be explored. These findings suggest that patients are likely to receive conflicting breast cancer screening recommendations from different providers. Copyright (C) 2014 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Corbelli, Jennifer; Borrero, Sonya; Kraemer, Kevin; Rubio, Doris; McNeil, Melissa] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Res Hlth Equ & Promot, Pittsburgh, PA USA. [Borrero, Sonya; Kraemer, Kevin; Rubio, Doris; Karpov, Irina] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Bonnema, Rachel] Univ Nebraska Med Ctr, Div Gen Internal Med, Omaha, NE USA. [McNamara, Megan] Case Western Reserve Univ, Sch Med, Div Gen Internal Med, Cleveland, OH USA. [McNamara, Megan] Louis Stokes VA Healthcare Syst, Cleveland, OH USA. RP Corbelli, J (reprint author), 200 Lothrop St,MUH 9W-33, Pittsburgh, PA 15213 USA. EM corbellija@upmc.edu NR 48 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2014 VL 24 IS 3 BP E313 EP E319 DI 10.1016/j.whi.2014.03.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1ZQ UT WOS:000341114600008 PM 24794545 ER PT J AU Craig, AD Dehlendorf, C Borrero, S Harper, CC Rocca, CH AF Craig, Amaranta D. Dehlendorf, Christine Borrero, Sonya Harper, Cynthia C. Rocca, Corinne H. TI Exploring Young Adults' Contraceptive Knowledge and Attitudes: Disparities by Race/Ethnicity and Age SO WOMENS HEALTH ISSUES LA English DT Article ID 2002 NATIONAL-SURVEY; LOW-INCOME WOMEN; UNITED-STATES; UNINTENDED PREGNANCY; FAMILY GROWTH; RISK; CHOICE; DISCONTINUATION; HEALTH; SAMPLE AB Background: Half of pregnancies in the United States are unintended, with the highest proportions occurring among Blacks, Hispanics, and teenagers. Understanding differences in knowledge and attitudes about contraception by race/ethnicity and age can improve efforts to reduce disparities in unintended pregnancy. Methods: This analysis used data from the 897 female respondents in National Survey of Reproductive and Contraceptive Knowledge, a survey exploring young adults' knowledge and attitudes about contraception and pregnancy. Bivariate and multivariate logistic regression analyses were used to assess racial/ethnic and age group differences in knowledge and attitudes about contraceptives. Findings: Hispanics and teenagers (aged 18-19) had lower awareness of available contraceptive methods, and lower knowledge about individual methods compared with White women and young adults (age 20-29). For example, Hispanics (74%) and teenagers (77%) were less likely to have heard of the intrauterine device (IUD) than were White women (90%) and young adults (90%), and were less likely to know that a woman experiencing side effects could switch brands of oral contraceptive pills (72% of Hispanics vs. 86% of White women; 76% of teenagers vs. 90% of young adults). Hispanics born outside the United States had lower knowledge about contraceptives than U.S.-born Hispanics. For example, foreign-born Hispanics were less likely than U.S.-born Hispanics to have heard of the IUD (59% vs. 82%) or the vaginal ring (55% vs. 95%). Conclusions: Lower contraceptive knowledge among teenagers and Hispanics, particularly immigrants, suggests the importance of disseminating family planning information to these women as one means to address disparities in unintended pregnancy. Copyright (C) 2014 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Craig, Amaranta D.; Dehlendorf, Christine] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Craig, Amaranta D.; Dehlendorf, Christine; Harper, Cynthia C.; Rocca, Corinne H.] Univ Calif San Francisco, Bixby Ctr Global Reprod Hlth, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Borrero, Sonya] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Craig, AD (reprint author), Univ Calif San Francisco, Dept Family & Community Med, 1001 Potrero Ave,Ward 22, San Francisco, CA 94143 USA. EM amaranta.craig@ucsf.edu FU NICHD NIH HHS [1R21HD068736-01A1, K23 HD067197, K23HD067197, R21 HD068736]; NIMHD NIH HHS [R25 MD006832, R25MD006832] NR 40 TC 19 Z9 20 U1 4 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2014 VL 24 IS 3 BP E281 EP E289 DI 10.1016/j.whi.2014.02.003 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1ZQ UT WOS:000341114600004 PM 24725755 ER PT J AU Graff, JN Puri, S Bifulco, CB Fox, BA Beer, TM AF Graff, Julie N. Puri, Sachin Bifulco, Carlo B. Fox, Bernard A. Beer, Tomasz M. TI Sustained Complete Response to CTLA-4 Blockade in a Patient with Metastatic, Castration-Resistant Prostate Cancer SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID DOSE-ESCALATION TRIAL; IMMUNOTHERAPY; IPILIMUMAB; ANTIGEN; MUTATIONS; HYDROLASE; MELANOMA AB We present the case of a man with metastatic, castration-resistant prostate cancer, who had a complete prostate-specific antigen (PSA) response after 2(1/2) doses of ipilimumab. His treatment course was complicated by diarrhea and autoimmune hepatitis, both of which resolved within 4 months. Sera and biopsy specimens were accessed, and sera from pretreatment and day 113 were analyzed. Augmented antibody responses were detected against 11 potential tumor antigens, with responses ranging from 5- to 20-fold in day 113 sera compared with baseline. Genes that were targets of a strong antibody response (arbitrarily set at 10-fold or greater increase) were analyzed by real-time PCR for expression in the tumor biopsy cDNA. Of the top 5 genes, only 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) could be identified in the amplified tumor biopsy cDNA. Using an antibody to HIBCH, immunohistochemical analysis documented strong expression of the protein. Together, these data suggest that an augmented antibody response to HIBCH, an antigen that was expressed by the patient's prostate cancer, could have contributed to the clinical response. After 16 months of PSA stability, he discontinued his androgen-suppression therapy. With the return of his testosterone, his PSA increased slightly, likely originating from his intact prostate. He has been disease free for the past 6 years without any additional therapy. (C) 2014 AACR. C1 [Graff, Julie N.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. [Graff, Julie N.; Fox, Bernard A.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Puri, Sachin; Bifulco, Carlo B.; Fox, Bernard A.] Providence Canc Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR USA. [Bifulco, Carlo B.] Providence Hlth Syst, Dept Pathol, Portland, OR USA. RP Graff, JN (reprint author), Oregon Hlth & Sci Univ, 3303 SW Bond Ave,CH14R, Portland, OR 97239 USA. EM graffj@ohsu.edu FU Bristol-Myers Squibb FX C.B. Bifulco is a consultant/advisory board member for EMD/Serono. J.N. Graff, B.A. Fox, and T.M. Beer have received commercial research support from Bristol-Myers Squibb. NR 21 TC 9 Z9 9 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD MAY PY 2014 VL 2 IS 5 BP 399 EP 403 DI 10.1158/2326-6066.CIR-13-0193 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA AM7GT UT WOS:000340034200003 PM 24795352 ER PT J AU Spaccarelli, N Gharavi, M Saboury, B Cheng, G Rook, AH Alavi, A AF Spaccarelli, Natalie Gharavi, Mohammad Saboury, Babak Cheng, Gang Rook, Alain H. Alavi, Abass TI Role of F-18-fluorodeoxyglucose positron emission tomography imaging in the management of primary cutaneous lymphomas SO HELLENIC JOURNAL OF NUCLEAR MEDICINE LA English DT Review DE Lymphoma; Skin cancer; F-18-FDG-PET; Staging lymphoma; Lymphoma response to therapy; Recurrence ID T-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; MYCOSIS-FUNGOIDES; FDG-PET/CT; COMPUTED-TOMOGRAPHY; PROGNOSTIC VALUE; SEZARY-SYNDROME; F-18 FLUORODEOXYGLUCOSE; INTERNATIONAL-SOCIETY; TREATMENT RESPONSE AB Primary cutaneous lymphomas (PCLs) include both cutaneous T-cell and B-cell lymphomas and comprise the second most common type of extra-nodal non-Hodgkin's lymphomas. The treatment and prognosis of PCLs typically depend on the extent of disease. In evaluating extent of disease in oncological processes, computed tomography (CT) provides a purely anatomical assessment of disease. In comparison, [F-18]-fluorodeoxyglucose positron emission tomography (F-18-FDG PET) both visualizes and quantifies the biological processes occurring in the disease at the cellular level. This paper reviews the available literature addressing the clinical role of F-18-FDG PET both alone and in combination with CT in PCLs and draws several conclusions. While F-18-FDG PET seems superior to CT in its detection of nodal and cutaneous PCL lesions,F-18-FDG PET does not seem to adequately detect erythroderma, plaque, or patch cutaneous PCL lesions. In addition, several case series have demonstrated that physicians may be able to use the semi-quantitative measurement of F-18-FDG uptake provided by F-18-FDG PET to predict which lesions are most aggressive. Other case series have shown that the integrated F-18-FDG PET/CT may provide an objective measure of treatment response in patients with PCLs. C1 [Spaccarelli, Natalie; Alavi, Abass] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gharavi, Mohammad; Saboury, Babak; Alavi, Abass] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Cheng, Gang] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Rook, Alain H.] Hosp Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Alavi, A (reprint author), Hosp Univ Penn, 3400 Spruce St 4283, Philadelphia, PA 19104 USA. EM abass.alavi@uphs.upenn.edu NR 40 TC 4 Z9 4 U1 0 U2 1 PU HELLENIC SOC NUCLEAR MEDICINE PI THESSALONIKI PA 51 HERMU ST, THESSALONIKI, 546 23, GREECE SN 1790-5427 J9 HELL J NUCL MED JI Hell. J. Nucl. Med. PD MAY-AUG PY 2014 VL 17 IS 2 BP 78 EP 84 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AM7CZ UT WOS:000340023600002 PM 24997076 ER PT J AU Thukkani, AK Fonarow, GC Cannon, CP Cox, M Hernandez, AF Peterson, ED Peacock, WF Laskey, WK Schwamm, LH Bhatt, DL AF Thukkani, Arun K. Fonarow, Gregg C. Cannon, Christopher P. Cox, Margueritte Hernandez, Adrian F. Peterson, Eric D. Peacock, W. Frank Laskey, Warren K. Schwamm, Lee H. Bhatt, Deepak L. CA Guidelines Steering Comm TI Quality of Care for Patients With Acute Coronary Syndromes as a Function of Hospital Revascularization Capability: Insights From Get With The Guidelines-CAD SO CLINICAL CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; AMERICAN-HEART-ASSOCIATION; SECONDARY PREVENTION; MANAGEMENT; ADHERENCE; MORTALITY AB Background Revascularization availability at US hospitals varies and may impact care quality for acute coronary syndrome patients. Hypothesis The hypothesis of this study was that there would be differences in care quality at Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) hospitals based on revascularization capability. Methods For acute coronary syndrome patients admitted to GWTG-CAD hospitals between 2000 and 2010, care quality at hospitals with or without revascularization capability was examined by assessing conformity with performance and quality measures. Results This study included 95 999 acute coronary syndrome patients admitted to 310 GWTG-CAD hospitals. There were 89 000 patients admitted to 226 revascularization-capable hospitals and 6999 patients admitted to 84 hospitals without revascularization capability included. Adjusted multivariate analysis demonstrated that 8 of the 19 measures were more frequently performed in the revascularization cohort: aspirin (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.04-1.92), clopidogrel (OR: 2.31, 95% CI: 1.78-3.00), lipid-lowering therapies at discharge (OR: 1.39, 95% CI: 1.04-1.87), lipid-lowering therapies for low-density lipoprotein >100 mg/dL (OR: 1.85, 95% CI: 1.23-2.77), achievement of blood pressure <140/90 mm Hg (OR: 1.20, 95% CI: 1.03-1.40), LDL recorded (OR: 1.47, 95% CI: 1.05-2.06), and recommendations offered for physical activity (OR: 3.82, 95% CI: 2.23-6.55) or weight management (OR: 1.74, 95% CI: 1.12-2.69). Conclusions The GWTG-CAD revascularization hospitals were associated with better performance in some, but not all, measures assessed. Although the difference in conformity between hospital types was modest for performance measures but more variable for quality measures, room for improvement exists in key aspects of care. C1 [Thukkani, Arun K.; Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Thukkani, Arun K.; Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, UCLA Div Cardiol, Los Angeles, CA USA. [Cox, Margueritte; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Div Cardiol, Albuquerque, NM 87131 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bhatt, DL (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Cardiorentis; Roche; Medicine's Company; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Accumetrics; CSL Behring; Essentialis; GlaxoSmithKline; Merck; Regeneron; Sanofi; Takeda FX Dr. W. Frank Peacock discloses the following relationships - Research Grants: Cardiorentis, Roche, The Medicine's Company. Consultant: Abbott, Alere, BG Medicine, Cardiorentis, Janssen, The Medicine's Company. Ownership Interest: Comprehensive Research Associates LLC, Emergencies in Medicine LLC. Dr. Deepak L. Bhatt discloses the following relationships: research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; advisory board for Elsevier PracticeUpdate Cardiology, Medscape Cardiology, and Regado Biosciences; board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; chair of the American Heart Association Get With The Guidelines Steering Committee; honoraria from the American College of Cardiology (editor, Clinical Trials, CardioSource), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Population Health Research Institute (clinical trial steering committee), SLACK Incorporated (chief medical editor, Cardiology Today's Intervention), and WebMD (CME steering committees). Additional relationships for Dr. Bhatt: senior associate editor for Journal of Invasive Cardiology; data-monitoring committees with Duke Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; and unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Christopher P. Cannon discloses the following relationships: research grants from Accumetrics, AstraZeneca, CSL Behring, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda; advisory board for Alnylam, Bristol-Myers Squibb, LipimetiX Development LLC, and Pfizer; and clinical advisor for and equity in Automedics Medical Systems. NR 17 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 2014 VL 37 IS 5 BP 285 EP 292 DI 10.1002/clc.22246 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH0IK UT WOS:000335802400004 PM 24452828 ER PT J AU Fitzgibbons, PL Dillon, DA Alsabeh, R Berman, MA Hayes, DF Hicks, DG Hughes, KS Nofech-Mozes, S AF Fitzgibbons, Patrick L. Dillon, Deborah A. Alsabeh, Randa Berman, Michael A. Hayes, Daniel F. Hicks, David G. Hughes, Kevin S. Nofech-Mozes, Sharon CA Coll Amer Pathologists TI Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Breast SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; ESTROGEN-RECEPTOR STATUS; IN-SITU HYBRIDIZATION; COLD ISCHEMIC TIME; PROGESTERONE-RECEPTORS; AMERICAN-SOCIETY; CANCER; IMMUNOHISTOCHEMISTRY; EXPRESSION; FIXATION C1 [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA 92835 USA. [Dillon, Deborah A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Alsabeh, Randa] Kaiser Permanente, Los Angeles Med Ctr, Dept Pathol, Los Angeles, CA USA. [Berman, Michael A.] Jefferson Hosp, Dept Pathol, Jefferson Hills, PA USA. [Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Hicks, David G.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Nofech-Mozes, Sharon] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Anat Pathol, Toronto, ON, Canada. RP Fitzgibbons, PL (reprint author), St Jude Med Ctr, Dept Pathol, 101 E Valencia Mesa Dr, Fullerton, CA 92835 USA. EM Patrick.Fitzgibbons@stjoe.org OI Fitzgibbons, Patrick/0000-0002-2998-6913; Hughes, Kevin/0000-0003-4084-6484 NR 28 TC 10 Z9 11 U1 0 U2 1 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2014 VL 138 IS 5 BP 595 EP 601 DI 10.5858/arpa.2013-0566-CP PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AM0TX UT WOS:000339560900009 PM 24236805 ER PT J AU Lee, H Schlereth, SL Park, EY Emami-Naeini, P Chauhan, SK Dana, R AF Lee, HyunSoo Schlereth, Simona L. Park, Eun Y. Emami-Naeini, Parisa Chauhan, Sunil K. Dana, Reza TI A Novel Pro-Angiogenic Function for Interferon-gamma-Secreting Natural Killer Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE endothelial cells; neovascularization; NK cells; macrophages; interferons ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; ENDOTHELIAL GROWTH-FACTOR; NK CELLS; MACULAR DEGENERATION; EYE DISEASE; T-CELLS; INHIBITION; INTERLEUKIN-12; INDUCTION; PHENOTYPE AB PURPOSE. To explore the function of natural killer (NK) cells in inflammatory angiogenesis in mice. METHODS. To study ocular angiogenic responses we used the cornea BFGF micropellet and the laser-induced choroidal neovascularization (CNV) mouse models (C57BL/6). To deplete NK cells in these models, we injected an anti-NK1.1 antibody or an isotype antibody as a control. Corneas or choroids were immunohistochemically stained for blood vessels (CD31), macrophages (F4/80), or CNV (isolectin-IB4). Vascular endothelial growth factors (VEGF), IFN-gamma, or TNF-alpha levels were measured by real-time quantitative PCR (qPCR) or flow cytometry. A coculture assay of macrophages, NK cells, and human umbilical vein endothelial cells (HUVECs) was analyzed morphometrically to examine the ability of NK cells to induce angiogenesis in vitro. RESULTS. Our data demonstrate that in vivo depletion of NK cells leads to a significant reduction of corneal angiogenesis and CNV. Furthermore, NK cell depletion reduces macrophage infiltration into the cornea and mRNA expression levels of VEGF-A, VEGF-C, and VEGFR3 at day 7 after micropellet insertion. In the laser-induced CNV model, our data show that NK cell depletion leads to decreased areas of CNV and significantly reduced mRNA expression of VEGFs and IFN-gamma in the choroid. An in vitro coculture assay shows an IFN-gamma-dependent increase in VEGF expression levels, thereby increasing endothelial cell proliferation. CONCLUSIONS. Our findings demonstrate a novel pro-angiogenic function for NK cells, indicating that IFN-gamma-secreting NK cells can induce angiogenesis by promoting enhanced VEGF expression by macrophages. C1 [Lee, HyunSoo; Schlereth, Simona L.; Park, Eun Y.; Emami-Naeini, Parisa; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. [Lee, HyunSoo] Catholic Univ Korea Seoul, Seoul St Mary Hosp, Dept Ophthalmol, Coll Med, Seoul, South Korea. [Lee, HyunSoo] Catholic Univ Korea Seoul, Seoul St Mary Hosp, Catholic Inst Visual Sci, Coll Med, Seoul, South Korea. [Schlereth, Simona L.] Univ Cologne, Dept Ophthalmol, D-50931 Cologne, Germany. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institutes of Health/National Eye Institutes [R01-12963] FX Supported by grants from the National Institutes of Health/National Eye Institutes R01-12963 (RD). NR 29 TC 11 Z9 11 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2014 VL 55 IS 5 BP 2885 EP 2892 DI 10.1167/iovs.14-14093 PG 8 WC Ophthalmology SC Ophthalmology GA AL9TP UT WOS:000339484800010 PM 24713481 ER PT J AU Chatterjee, A Villarreal, G Oh, DJ Kang, MH Rhee, DJ AF Chatterjee, Ayan Villarreal, Guadalupe, Jr. Oh, Dong-Jin Kang, Min Hyung Rhee, Douglas J. TI AMP-Activated Protein Kinase Regulates Intraocular Pressure, Extracellular Matrix, and Cytoskeleton in Trabecular Meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE AMPK; POAG; glaucoma; trabecular meshwork; intraocular pressure; SPARC; TGF-beta 2; RhoA ID OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR DYNAMICS; GROWTH-FACTOR BETA-2; MICE EXHIBIT; NONINVASIVE MEASUREMENT; FISTULIZING SURGERY; OUTFLOW RESISTANCE; JUVENILE GLAUCOMA; GENETIC-LINKAGE; ORGAN-CULTURE AB PURPOSE. In this study, we investigate how adenosine monophosphate-activated protein kinase (AMPK) affects extracellular matrix (ECM) and cellular tone in the trabecular meshwork (TM), and examine how deletion of its catalytic alpha 2 subunit affects IOP and aqueous humor clearance in mice. METHODS. Human TM tissue was examined for expression of AMPK alpha 1 and AMPK alpha 2, genomically distinct isoforms of the AMPK catalytic subunit. Primary cultured human TM cells were treated for 24 hours with the AMPK activator 5-amino-1-beta-Dffff-ribofuranosyl-imidazole-4-carboxamide (AICAR), under basal or TGF-beta 2 stimulatory conditions. Conditioned media (CM) was probed for secreted protein acidic and rich in cysteine (SPARC), thrombospondin-1 (TSP-1), and ECM proteins, and cells were stained for F-actin. Cells underwent adenoviral infection with a dominant negative AMPK alpha subunit (ad.DN.AMPK alpha) and were similarly analyzed. Intraocular pressure, central corneal thickness (CCT), and aqueous clearance were measured in AMPK alpha 2-null and wild-type (WT) mice. RESULTS. Both AMPK alpha 1 and AMPK alpha 2 are expressed in TM. AICAR activated AMPKa and suppressed the expression of various ECM proteins under basal and TGF-beta 2 stimulatory conditions. AICAR decreased F-actin staining and increased the phospho-total RhoA ratio (Ser188). Transforming growth factor-beta 2 transiently dephosphorylated AMPK alpha. Infection with ad.DN.AMPK alpha upregulated various ECM proteins, decreased the phospho-total RhoA ratio, and increased F-actin staining. AMPK alpha 2-null mice exhibited 6% higher IOP and decreased aqueous clearance compared with WT mice, without significant differences in CCT or angle morphology. CONCLUSIONS. Collectively, our data identify AMPK as a critical regulator of ECM homeostasis and cytoskeletal arrangement in the TM. Mice that are AMPK alpha 2-null exhibit higher IOPs and decreased aqueous clearance than their WT counterparts. C1 [Chatterjee, Ayan; Villarreal, Guadalupe, Jr.; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU National Eye Institute (Bethesda, MD, USA) [EY 019654-01, EY 014104]; Howard Hughes Medical Institute (Chevy Chase, MD, USA) FX Supported by grants from National Eye Institute (Bethesda, MD, USA) EY 019654-01 (DJR) and EY 014104 (Massachusetts Eye and Ear Infirmary Vision-Core Grant), and the Howard Hughes Medical Institute (Chevy Chase, MD, USA) Research Training Fellowship for Medical Students (AC). NR 91 TC 5 Z9 5 U1 0 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2014 VL 55 IS 5 BP 3127 EP 3139 DI 10.1167/iovs.13-12755 PG 13 WC Ophthalmology SC Ophthalmology GA AL9TP UT WOS:000339484800040 PM 24713487 ER PT J AU Jackson, GR Scott, IU Kim, IK Quillen, DA Iannaccone, A Edwards, JG AF Jackson, Gregory R. Scott, Ingrid U. Kim, Ivana K. Quillen, David A. Iannaccone, Alessandro Edwards, John G. TI Author Response: Additional Considerations in the Utility of Dark Adaptometry for the Diagnosis of Age-Related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter ID PREVALENCE C1 [Jackson, Gregory R.; Scott, Ingrid U.; Quillen, David A.] Penn State Coll Med, Penn State Hershey Eye Ctr, Hershey, PA 17033 USA. [Kim, Ivana K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Iannaccone, Alessandro] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Edwards, John G.] MacuLogix Inc, Hummelstown, PA USA. RP Jackson, GR (reprint author), Penn State Coll Med, Penn State Hershey Eye Ctr, Hershey, PA 17033 USA. EM gjackson@maculogix.com NR 6 TC 0 Z9 0 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2014 VL 55 IS 5 BP 3149 EP 3149 DI 10.1167/iovs.14-14569 PG 1 WC Ophthalmology SC Ophthalmology GA AL9TP UT WOS:000339484800043 PM 24840311 ER PT J AU DiPasquale, DM Strangman, GE Muza, SR AF DiPasquale, Dana M. Strangman, Gary E. Muza, Stephen R. TI Comparing the Effects of Exercise in Hypobaric and Normobaric Hypoxia on Acute Mountain Sickness SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [DiPasquale, Dana M.; Strangman, Gary E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Muza, Stephen R.] US Army Res Inst Environm Med, Thermal & Mt Med Div, Natick, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 1564 BP 425 EP 425 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115903009 ER PT J AU Scarborough, DM Kramer, MD Sanchez, JE Loughlin, JW Berkson, EM AF Scarborough, Donna M. Kramer, Matthew D. Sanchez, Javier E. Loughlin, Jesse W. Berkson, Eric M. TI Comparison Of Forces At The Elbow During Pitching And Catching: Single Subject Study SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Scarborough, Donna M.; Kramer, Matthew D.; Sanchez, Javier E.; Loughlin, Jesse W.; Berkson, Eric M.] Massachusetts Gen Hosp, Foxboro, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 1945 BP 531 EP 532 PG 2 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115903304 ER PT J AU La Fountaine, MF Cirnigliaro, CM Kirshblum, SC Galea, M Spungen, AM Bauman, WA AF La Fountaine, Michael F. Cirnigliaro, Christopher M. Kirshblum, Steven C. Galea, Marinella Spungen, Ann M. Bauman, William A. TI The Role of Severe Physical Inactivity on High Density Lipoprotein Particle Size and Number: Perspectives from NMR Spectroscopy in Persons with Chronic Spinal Cord Injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [La Fountaine, Michael F.] Seton Hall Univ, S Orange, NJ 07079 USA. [Cirnigliaro, Christopher M.; Galea, Marinella; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2372 BP 636 EP 636 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115904177 ER PT J AU Cirnigliaro, CM Dengel, DR Liu, J LaFountaine, MF Kirshblum, SC Galea, M Spungen, AM Bauman, WA AF Cirnigliaro, Christopher M. Dengel, Donald R. Liu, Ji LaFountaine, Michael F. Kirshblum, Steven C. Galea, Marinella Spungen, Ann M. Bauman, William A. TI Increased Visceral Fat in Persons with Spinal Cord Injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Cirnigliaro, Christopher M.; LaFountaine, Michael F.; Galea, Marinella; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Dengel, Donald R.] Univ Minnesota, Minneapolis, MN USA. [Liu, Ji] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2940 BP 800 EP 800 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115905271 ER PT J AU La Fountaine, MF Toda, M Testa, A Bauman, WA AF La Fountaine, Michael F. Toda, Michita Testa, Anthony Bauman, William A. TI The Spontaneous Appearance Of Wandering Atrial Pacemaker And Frequent Atrial Ectopy Following Concussion SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [La Fountaine, Michael F.; Toda, Michita; Testa, Anthony] Seton Hall Univ, S Orange, NJ 07079 USA. [Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 3202 BP 865 EP 865 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115905458 ER PT J AU Dittmer, TA Sahni, N Kubben, N Hill, DE Vidal, M Burgess, RC Roukos, V Misteli, T AF Dittmer, Travis A. Sahni, Nidhi Kubben, Nard Hill, David E. Vidal, Marc Burgess, Rebecca C. Roukos, Vassilis Misteli, Tom TI Systematic identification of pathological lamin A interactors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; GILFORD-PROGERIA-SYNDROME; PROTEIN-PROTEIN INTERACTIONS; NUCLEAR LAMIN; AUTOSOMAL-DOMINANT; LMNA GENE; COMPOUND HETEROZYGOSITY; DILATED CARDIOMYOPATHY; PARTIAL LIPODYSTROPHY; MUTATION ANALYSIS AB Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by > 300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype-phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A-binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome-wide ORFeome library, we identified and validated 337 lamin A-binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson-Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)-like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein-protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes. C1 [Dittmer, Travis A.; Kubben, Nard; Burgess, Rebecca C.; Roukos, Vassilis; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. [Sahni, Nidhi; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov RI Roukos, Vassilis/K-6248-2012 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Progeria Research Foundation; National Institutes of Health [HG001715, HG006066] FX We thank Song Yi, Sam Pevzner, Ty Voss, and Orna Cohen-Fix for technical expertise. Imaging was performed in the National Cancer Institute High-Throughput Imaging Facility. This work was in part supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, the Progeria Research Foundation, and National Institutes of Health grants HG001715 and HG006066. NR 69 TC 11 Z9 11 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 1 PY 2014 VL 25 IS 9 BP 1493 EP 1510 DI 10.1091/mbc.E14-02-0733 PG 18 WC Cell Biology SC Cell Biology GA AM2AJ UT WOS:000339650200008 PM 24623722 ER PT J AU Sittig, DF Ash, JS Singh, H AF Sittig, Dean F. Ash, Joan S. Singh, Hardeep TI The SAFER Guides: Empowering Organizations to Improve the Safety and Effectiveness of Electronic Health Records SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PROVIDER ORDER ENTRY; PATIENT-SAFETY; FOLLOW-UP; INFORMATICS; SYSTEMS AB Electronic health records (EHRs) have potential to improve quality and safety of healthcare. However, EHR users have experienced safety concerns from EHR design and usability features that are not optimally adapted for the complex work flow of real-world practice. Few strategies exist to address unintended consequences from implementation of EHRs and other health information technologies. We propose that organizations equipped with EHRs should consider the strategy of "proactive risk assessment" of their EHR-enabled healthcare system to identify and address EHR-related safety concerns. In this paper, we describe the conceptual underpinning of an EHR-related self-assessment strategy to provide institutions a foundation upon which they could build their safety efforts. With support from the Office of the National Coordinator for Health Information Technology (ONC), we used a rigorous, iterative process to develop a set of 9 self-assessment tools to optimize the safety and safe use of EHRs. These tools,referred to as the Safety Assurance Factors for EHR Resilience (SAFER) guides, could be used to self-assess safety and effectiveness of EHR implementations, identify specific areas of vulnerability, and create solutions and culture change to mitigate risks. A variety of audiences could conduct these assessments, including frontline clinicians or care teams in different practices, or clinical, quality, or administrative leaders within larger institutions. The guides use a multifaceted systems-based approach to assess risk and empower organizations to work with internal or external stakeholders (eg, EHR developers) on optimizing EHR functionality and using EHRs to drive improvements in the quality and safety of healthcare. C1 [Sittig, Dean F.] Univ Texas Hlth Sci Ctr Houston, Houstons Sch Biomed Informat, Houston, TX 77030 USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX 77030 USA. [Ash, Joan S.] Oregon Hlth & Sci Univ, Sch Med, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Singh, Hardeep] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Vet Adm Hlth Serv Res, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dev Ctr Innovat Qual Effectiveness & Safety, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Sittig, DF (reprint author), UT Mem Hermann Ctr Healthcare Qual & Safety, 6410 Fannin St,UTPB 1100-43, Houston, TX 77030 USA. EM dean.f.sittig@uth.tmc.edu FU Westat - Office of the National Coordinator for Health Information Technology (ONC) [HHSP-23320095655WC0095655, HH-SP23337003T]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX Source of Funding:. The SAFER project is supported through a subcontract from Westat (HHSP-23320095655WC0095655; Anticipating the Unintended Consequences of Health IT) funded by the Office of the National Coordinator for Health Information Technology (ONC) (HH-SP23337003T; to Drs Sittig, Ash, and Singh). Dr Singh was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 32 TC 14 Z9 14 U1 2 U2 5 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 MAY PY 2014 VL 20 IS 5 BP 418 EP 423 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AL5AV UT WOS:000339146800012 PM 25181570 ER PT J AU Barnett, PG Chow, A Joyce, VR Bayoumi, AM Griffin, SC Sun, H Holodniy, M Brown, ST Cameron, DW Sculpher, M Youle, M Anis, AH Owens, DK AF Barnett, Paul G. Chow, Adam Joyce, Vilija R. Bayoumi, Ahmed M. Griffin, Susan C. Sun, Huiying Holodniy, Mark Brown, Sheldon T. Cameron, D. William Sculpher, Mark Youle, Mike Anis, Aslam H. Owens, Douglas K. TI Effect of Management Strategies and Clinical Status on Costs of Care for Advanced HIV SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; HEALTH-CARE; LIFETIME COST; UNITED-STATES; ERA; EXPENDITURES; MEDICAID; PATTERNS; MODELS AB Objectives To determine the association between preexisting characteristics and current health and the cost of different types of advanced human immunodeficiency virus (HIV) care. Methods Treatment-experienced patients failing highly active antiretroviral treatment (ART) in the United States, Canada, and the United Kingdom were factorial randomized to an antiretroviral-free period and ART intensification. Cost was estimated by multiplying patient-reported utilization by a unit cost. Results A total of 367 participants were followed for a mean of 15.3 quarters (range 1-26). Medication accounted for most (61.8%) of the $26,832 annual cost. Cost averaged $4147 per quarter for ART, $1981 for inpatient care, $580 for outpatient care, and $346 for other medications. Cost for inpatient stays, outpatient visits, and other medications was 171% higher (P<.01) and cost of ART was 32% lower (P<.01) when cluster of differentiation 4 (CD4) count was <50 cells/mu L compared with periods when CD4 count was >200 cells/mu L. Some baseline characteristics, including low CD4 count, high viral load, and HIV from injection drug use with hepatitis C coinfection, had a sustained effect on cost. Conclusions The association between health status and cost depended on the type of care. Indicators of poor health were associated with higher inpatient and concomitant medication costs and lower cost for ART medication. Although ART has supplanted hospitalization as the most important cost in HIV care, some patients continue to incur high hospitalization costs in periods when they are using less ART. The cost of interventions to improve the use of ART might be offset by the reduction of other costs. C1 [Barnett, Paul G.; Chow, Adam; Joyce, Vilija R.] VA HSR&D Hlth Econ Res Ctr, VA Palo Alto Healthcare Syst, VA Cooperative Studies Program, Menlo Pk, CA 94025 USA. [Bayoumi, Ahmed M.] St Michaels Hosp, Ctr Res Inner City Hlth, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Bayoumi, Ahmed M.] St Michaels Hosp, Div Gen Internal Med, Toronto, ON, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Med, Dept Hlth Policy, Dept Management & Evaluat, Toronto, ON, Canada. [Griffin, Susan C.; Sculpher, Mark] Univ York, Ctr Hlth Econ, York, N Yorkshire, England. [Holodniy, Mark; Owens, Douglas K.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Owens, Douglas K.] Stanford Univ, Ctr Primary Care & Outcomes Res, Ctr Hlth Policy, Stanford, CA USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA. [Cameron, D. William] Univ Ottawa, Ottawa Hosp, Div Infect Dis, Ottawa, ON, Canada. [Youle, Mike] Royal Free Hosp, London, England. [Sun, Huiying; Anis, Aslam H.] CIHR, Canadian HIV Trials Network, Vancouver, BC, Canada. [Anis, Aslam H.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada. RP Barnett, PG (reprint author), HERC, VA Palo Alto Hlth Care Syst, 795 Willow Rd 152, Menlo Pk, CA 94025 USA. EM paul.barnett@va.gov RI Joyce, Vilija/A-2578-2013 OI Joyce, Vilija/0000-0002-2484-4625 FU US Department of Veterans Affairs Cooperative Studies Program; United Kingdom Medical Research Council; Canadian Institutes for Health Research FX Source of Funding: US Department of Veterans Affairs Cooperative Studies Program, the United Kingdom Medical Research Council, and the Canadian Institutes for Health Research. NR 36 TC 2 Z9 2 U1 0 U2 2 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 MAY PY 2014 VL 20 IS 5 BP E129 EP E137 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AL5AV UT WOS:000339146800002 PM 25326927 ER PT J AU Fagerness, J Fonseca, E Hess, GP Scott, R Gardner, KR Koffler, M Fava, M Perlis, RH Brennan, FX Lombard, J AF Fagerness, Jesen Fonseca, Eileen Hess, Gregory P. Scott, Rachel Gardner, Kathryn R. koffler, Michael Fava, Maurizio Perlis, Roy H. Brennan, Francis X. Lombard, Jay TI Pharmacogenetic-Guided Psychiatric Intervention Associated With Increased Adherence and Cost Savings SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID TREATMENT-RESISTANT DEPRESSION; GENE PROMOTER POLYMORPHISM; PROPENSITY SCORE METHODS; SERIOUS MENTAL-ILLNESS; ANTIDEPRESSANT RESPONSE; MEDICATION ADHERENCE; MAJOR DEPRESSION; SCHIZOPHRENIA; CARE; EPIDEMIOLOGY AB Objectives Pharmacogenetic testing as a means of guiding treatment decisions is beginning to see wider clinical use in psychiatry. The utility of this genetic information as it pertains to clinical decision making, treatment effectiveness, cost savings, and patient perception has not been fully characterized. Study Design In this retrospective study, we examined health claims data in order to assess medication adherence rates and healthcare costs for psychiatric patients. Methods Individuals for whom pharmacogenetic testing was ordered (cases) were contrasted with those who did not undergo such testing (controls). Cases and controls were propensity score matched in order to minimize risk of confounding in this nonrandomized study. An initial analysis of 111 cases and 222 controls examined both adherence and healthcare costs. A replication study of 116 cases and 232 controls examined adherence alone, as cost data was not available for this latter cohort. Results Overall, individuals with assay-guided treatment were significantly more medication adherent (P. 1.56 x 10(-3); Cohen's d = 0.511) than patients with standard treatment and demonstrated a relative cost savings of 9.5% in outpatient costs over a 4-month follow-up period, or $562 in total savings. Conclusions The data show the utility of pharmacogenetic testing in everyday psychiatric clinical practice, as it can lead to improved patient adherence and decreased healthcare costs. C1 [Fagerness, Jesen; Scott, Rachel; Gardner, Kathryn R.; koffler, Michael; Brennan, Francis X.; Lombard, Jay] Genomind LLC, Chalfont, PA 18914 USA. [Fonseca, Eileen; Hess, Gregory P.] Symphony Hlth Solut, Horsham, PA USA. [Hess, Gregory P.] Univ Penn, Leonard Davis Inst, Philadelphia, PA USA. [Fava, Maurizio; Perlis, Roy H.] Massachusetts Gen Hosp, Boston, MA USA. RP Scott, R (reprint author), Genomind LLC, 100 Highpoint Dr,Ste 102, Chalfont, PA 18914 USA. EM Rachel.Scott@genomind.com FU Genomind, LLC FX Source of Funding: This study was supported by funding from Genomind, LLC. NR 42 TC 12 Z9 13 U1 0 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 MAY PY 2014 VL 20 IS 5 BP E146 EP E156 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AL5AV UT WOS:000339146800004 PM 25326929 ER PT J AU Bonaca, MP Murphy, SA Miller, D Herrman, JPR Gottlieb, S Keltai, M Menozzi, A Nicolau, JC Widimsky, P Antman, EM Wiviott, SD AF Bonaca, Marc P. Murphy, Sabina A. Miller, Debra Herrman, Jean-Paul R. Gottlieb, Shmuel Keltai, Matyas Menozzi, Alberto Nicolau, Jose C. Widimsky, Petr Antman, Elliott M. Wiviott, Stephen D. TI Patterns of Long-term Thienopyridine Therapy and Outcomes in Patients With Acute Coronary Syndrome Treated With Coronary Stenting: Observations From the TIMI-38 Coronary Stent Registry SO CLINICAL CARDIOLOGY LA English DT Article ID DUAL-ANTIPLATELET THERAPY; DRUG-ELUTING STENTS; RANDOMIZED CLINICAL-TRIALS; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; ATHEROTHROMBOTIC EVENTS; SECONDARY PREVENTION; CLOPIDOGREL; THROMBOSIS; ASPIRIN AB Background The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) is not known. Factors influencing DAPT duration are not well described. Hypothesis We hypothesized that continued DAPT 12 months beyond ACS would be associated with patient factors such as stent type and that it may be associated with lower rates of ischemic events. Methods The TIMI 38 Coronary Stent Registry (CSR) followed patients who completed the TRITON-TIMI 38 trial, received a stent, and were alive and event free. Continuation of DAPT was determined by the treating physician. Results The CSR enrolled 2110 patients (1679>12 months from index ACS) and followed for a median of 2.1 additional years. DAPT was continued in 554 (26%) and was more likely to be continued in patients with drug-eluting stents (DES; 54%) and in North America. The rate of cardiovascular death, MI, or stroke was 2.35% per year, and 13 patients (0.6%) experienced Academic Research Consortium definite or probable ST. Recurrent ischemic events were similar between patients who continued thienopyridine therapy and those who stopped at registry entry (P = 0.74 for cardiovascular death/MI/stroke; P = 0.72 for definite or probable ST). After propensity score adjustment, there was no significant difference in cardiovascular death/MI/stroke (P = 0.55) or bleeding (P = 0.51) with prolonged DAPT. Conclusions Patients stabilized for a year after ACS and stenting have low rates of ST relative to overall cardiovascular events. The decision to continue DAPT maybe associated with stent type (DES vs bare-metal stent) and region. C1 [Bonaca, Marc P.; Murphy, Sabina A.; Antman, Elliott M.; Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Miller, Debra] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Herrman, Jean-Paul R.] Onze Lieve Vrouw Hosp, Dept Cardiol, Amsterdam, Netherlands. [Gottlieb, Shmuel] Shaare Zedek Med Ctr, Dept Cardiol, Inst Heart, Jerusalem, Israel. Chaim Sheba Med Ctr, Neufeld Cardiac Res Inst, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Keltai, Matyas] Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary. [Menozzi, Alberto] Azienda Osped Univ Parma, Parma, Italy. [Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Widimsky, Petr] Charles Univ Prague, Prague, Czech Republic. [Widimsky, Petr] Univ Hosp, Prague, Czech Republic. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org RI Nicolau, Jose/E-1487-2012; Widimsky, Petr/P-8088-2016 OI Widimsky, Petr/0000-0001-5686-7752 FU Daiichi Sankyo Co, Ltd; Eli Lilly and Co. FX This study was supported by a grant from Daiichi Sankyo Co, Ltd, and Eli Lilly and Co. NR 20 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 2014 VL 37 IS 5 BP 293 EP 299 DI 10.1002/clc.22247 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH0IK UT WOS:000335802400005 PM 24532082 ER PT J AU Menendez, ME Neuhaus, V Bot, AGJ Ring, D Johnson, AH AF Menendez, Mariano E. Neuhaus, Valentin Bot, Arjan G. J. Ring, David Johnson, A. Holly TI The Impact of Metabolic Syndrome on Inpatient Outcomes After Isolated Ankle Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE metabolic syndrome; ankle fracture; perioperative; complications; risk factors; mortality; discharge; epidemiology; outcome studies; trauma ID PERIOPERATIVE OUTCOMES; UNITED-STATES; CARDIOVASCULAR-DISEASE; OPERATIVE TREATMENT; TERM OUTCOMES; SURGERY; MORTALITY; TRENDS; PREVALENCE; OBESITY AB Background: Metabolic syndrome has been associated with increased morbidity following surgical procedures, yet its impact in acute orthopaedic trauma remains unclear. The purpose of this study was to evaluate the influence of metabolic syndrome on in-hospital (1) complications, (2) length of stay, and (3) nonroutine discharge in patients sustaining an isolated ankle fracture. Methods: Using the National Health Discharge Survey (NHDS) database for the years 2001 through 2007, an estimated 669 841 patients with isolated ankle fractures treated operatively were identified and separated into groups with and without metabolic syndrome. Multivariable binary logistic regression analysis was performed for each of the outcome variables. Results: Metabolic syndrome was an independent risk factor for increased nonroutine discharge (OR = 1.8) and the development of in-hospital complications (OR = 2.1). The presence of metabolic syndrome was not an independent risk factor for prolonged hospital stay. Conclusion: Patients with metabolic syndrome sustaining an isolated ankle fracture are at increased risk for in-hospital complications and a less rapid return of independent functional mobility, as evidenced by the higher need for posthospitalization care. Level of Evidence: Level III, epidemiologic study. C1 [Menendez, Mariano E.; Neuhaus, Valentin; Bot, Arjan G. J.; Ring, David; Johnson, A. Holly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ring, David; Johnson, A. Holly] Harvard Univ, Sch Med, Boston, MA USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St,Ste 2100, Boston, MA 02114 USA. EM marianofurrer@gmail.com OI Neuhaus, Valentin/0000-0003-4012-5628 NR 41 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2014 VL 35 IS 5 BP 463 EP 470 DI 10.1177/1071100714524555 PG 8 WC Orthopedics SC Orthopedics GA AL7QJ UT WOS:000339329400006 PM 24583475 ER PT J AU McMinn, D Oreskovic, NM Aitkenhead, MJ Johnston, DW Murtagh, S Rowe, DA AF McMinn, David Oreskovic, Nicolas M. Aitkenhead, Matt J. Johnston, Derek W. Murtagh, Shemane Rowe, David A. TI The physical environment and health-enhancing activity during the school commute: global positioning system, geographical information systems and accelerometry SO GEOSPATIAL HEALTH LA English DT Article DE school travel; physical activity; physical environment; children; global positioning systems; geographical information systems; Scotland ID PEACH PROJECT; CHILDREN; TRAVEL; GPS; TRANSPORTATION; INTENSITY; WALKING; DESIGN; TRENDS; GIS AB Active school travel is in decline. An understanding of the potential determinants of health-enhancing physical activity during the school commute may help to inform interventions aimed at reversing these trends. The purpose of this study was to identify the physical environmental factors associated with health-enhancing physical activity during the school commute. Data were collected in 2009 on 166 children commuting home from school in Scotland. Data on location and physical activity were measured using global positioning systems (GPS) and accelerometers, and mapped using geographical information systems (GIS). Multi-level logistic regression models accounting for repeated observations within participants were used to test for associations between each land-use category (road/track/path, other man-made, greenspace, other natural) and moderate-to-vigorous physical activity (MVPA). Thirty-nine children provided 2,782 matched data points. Over one third (37.1%) of children's school commute time was spent in MVPA. Children commuted approximately equal amounts of time via natural and man-made land-uses (50.2% and 49.8% respectively). Commuting via road/track/path was associated with increased likelihood of MVPA (Exp(B)= 1.23, P < 0.05), but this association was not seen for commuting via other manmade land-uses. No association was noted between greenspace use and MVPA, but travelling via other natural land-uses was associated with lower odds of MVPA (Exp(B)= 0.32, P < 0.05). Children spend equal amounts of time commuting to school via man-made and natural land-uses, yet man-made transportation route infrastructure appears to provide greater opportunities for achieving health-enhancing physical activity levels. C1 [McMinn, David] Univ Aberdeen, Rowett Inst Nutr & Hlth, Sch Med & Dent, Aberdeen AB25 2ZD, Scotland. [Oreskovic, Nicolas M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Res & Policy,MassGen, Boston, MA USA. [Aitkenhead, Matt J.] James Hutton Inst, Aberdeen, Scotland. [Johnston, Derek W.] Univ Aberdeen, Sch Psychol, Aberdeen AB25 2ZD, Scotland. [Murtagh, Shemane] Univ Brighton, Sch Hlth Profess, Eastbourne, England. [Rowe, David A.] Univ Strathclyde, Sch Psychol Sci & Hlth, Glasgow, Lanark, Scotland. RP McMinn, D (reprint author), Univ Aberdeen, Rowett Inst Nutr & Hlth, Sch Med & Dent, Hlth Sci Bldg,Ashgrove Rd, Aberdeen AB25 2ZD, Scotland. EM david.mcminn@abdn.ac.uk OI Oreskovic, Nicolas/0000-0001-8702-8636 NR 19 TC 1 Z9 1 U1 5 U2 21 PU UNIV NAPLES FEDERICO II PI NAPLES PA FAC VET MED, DEP PATHOLOGY & ANIMAL HEALTH, VET PARASITOLOGY, VIA DELLA VETERINARIA 1, NAPLES, 80137, ITALY SN 1827-1987 EI 1970-7096 J9 GEOSPATIAL HEALTH JI Geospatial Health PD MAY PY 2014 VL 8 IS 2 BP 569 EP 572 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AL6HF UT WOS:000339232500025 PM 24893034 ER PT J AU Cerimele, JM Halperin, AC Saxon, AJ AF Cerimele, Joseph M. Halperin, Abigail C. Saxon, Andrew J. TI Tobacco Use Treatment in Primary Care Patients with Psychiatric Illness SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Mental Disorders; Tobacco Use Cessation ID SMOKING-CESSATION PHARMACOTHERAPIES; RANDOMIZED CLINICAL-TRIAL; SEVERE MENTAL-ILLNESS; BIPOLAR DISORDER; CIGARETTE-SMOKING; MAJOR DEPRESSION; ANXIETY DISORDERS; HEALTH-SERVICES; UNITED-STATES; QUIT DAY AB The prevalence of smoking is higher in patients with psychiatric illness compared with the general population. Smoking causes chronic illnesses, which lead to premature mortality in those with psychiatric illness, is associated with greater burden of psychiatric symptoms, and contributes to the social isolation experienced by individuals with psychiatric disorders. Most patients with a psychiatric illness present initially to primary care rather than specialty care settings, and some patients receive care exclusively in the primary care setting. Therefore, family physicians and other primary care clinicians have an important role in the recognition and treatment of tobacco use disorders in patients with psychiatric illnesses. In this article we review common myths associated with smoking and psychiatric illness, techniques for implementing evidence-based tobacco use treatments, the evidence base for tobacco use treatment for patients with specific psychiatric diagnoses, and factors to consider when treating tobacco use disorders in patients with psychiatric illness. C1 [Cerimele, Joseph M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Halperin, Abigail C.] Univ Washington, Sch Med, Dept Family Med, Seattle, WA 98195 USA. [Halperin, Abigail C.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Cerimele, JM (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. EM cerimele@uw.edu FU National Institute of Mental Health [T-32 MH020021-16] FX JMC is supported by a grant from the National Institute of Mental Health (T-32 MH020021-16). NR 72 TC 3 Z9 4 U1 4 U2 12 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAY-JUN PY 2014 VL 27 IS 3 BP 399 EP 410 DI 10.3122/jabfm.2014.03.130252 PG 12 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AL5IL UT WOS:000339167000015 PM 24808119 ER PT J AU Guddati, AK Joy, PS Marak, CP AF Guddati, Achuta K. Joy, Parijat S. Marak, Creticus P. TI Dose adjustment of carboplatin in patients on peritoneal dialysis SO MEDICAL ONCOLOGY LA English DT Article DE Carboplatin; AUC; Dose; Peritoneal dialysis AB The Calvert equation has been extensively used to determine the dosage of carboplatin. However, in patients on dialysis, it predicts the same dosage regardless of the frequency of dialysis. Clearance of carboplatin during hemodialysis has been studied to a lesser extent, but there have been very few studies which have investigated the clearance of carboplatin in patients on peritoneal dialysis. A mathematical formula is proposed here to predict the dose of carboplatin for a given AUC in patients on peritoneal dialysis. This formula takes into account the frequency of dialysis sessions and the time delay between carboplatin infusion and the initiation of dialysis. The formula predicts an approximately similar dosage of carboplatin as that of the Calvert formula in patients undergoing peritoneal dialysis four times per day if dialysis is initiated 12 h after infusion. The formula may help in guiding the adjustment of carboplatin dose in patients who receive a lesser number of dialysis sessions per day and in those patients whose dialysis is initiated at different times (0-24 h) after carboplatin infusion. It is suggested that usage of this formula will result in a better dosage of carboplatin to suit specific dialysis frequencies in specific patients and eventually may result in a better efficacy and toxicity profile. C1 [Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02114 USA. [Joy, Parijat S.] Univ Iowa, Dept Internal Med, Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Marak, Creticus P.] Tahlequah City Hosp, Div Pulm Med, Dept Med, Tahlequah, OK 74464 USA. RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, 50 Fruit St, Boston, MA 02114 USA. EM aguddati@partners.org NR 5 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 EI 1559-131X J9 MED ONCOL JI Med. Oncol. PD MAY PY 2014 VL 31 IS 5 AR 946 DI 10.1007/s12032-014-0946-z PG 4 WC Oncology SC Oncology GA AL3CL UT WOS:000339002800022 PM 24706216 ER PT J AU Wang, J Mathalon, DH Roach, BJ Reilly, J Keedy, SK Sweeney, JA Ford, JM AF Wang, Jun Mathalon, Daniel H. Roach, Brian J. Reilly, James Keedy, Sarah K. Sweeney, John A. Ford, Judith M. TI Action planning and predictive coding when speaking SO NEUROIMAGE LA English DT Article DE Corollary discharge; Efference copy; IFG; STG ID HUMAN AUDITORY-CORTEX; COROLLARY DISCHARGE DYSFUNCTION; SPEECH PRODUCTION; NEUROMAGNETIC RESPONSES; OWN VOICE; SCHIZOPHRENIA; FEEDBACK; EEG; DYNAMICS; SOUNDS AB Across the animal kingdom, sensations resulting from an animal's own actions are processed differently from sensations resulting from external sources, with self-generated sensations being suppressed. A forward model has been proposed to explain this process across sensorimotor domains. During vocalization, reduced processing of one's own speech is believed to result from a comparison of speech sounds to corollary discharges of intended speech production generated from efference copies of commands to speak. Until now, anatomical and functional evidence validating this model in humans has been indirect. Using EEG with anatomical MRI to facilitate source localization, we demonstrate that inferior frontal gyrus activity during the 300 ms before speaking was associated with suppressed processing of speech sounds in auditory cortex around 100 ms after speech onset (N1). These findings indicate that an efference copy from speech areas in prefrontal cortex is transmitted to auditory cortex, where it is used to suppress processing of anticipated speech sounds. About 100 ms after N1, a subsequent auditory cortical component (P2) was not suppressed during talking. The combined N1 and P2 effects suggest that although sensory processing is suppressed as reflected in N1, perceptual gaps may be filled as reflected in the lack of P2 suppression, explaining the discrepancy between sensory suppression and preserved sensory experiences. These findings, coupled with the coherence between relevant brain regions before and during speech, provide new mechanistic understanding of the complex interactions between action planning and sensory processing that provide for differentiated tagging and monitoring of one's own speech, processes disrupted in neuropsychiatric disorders. Published by Elsevier Inc. C1 [Wang, Jun; Sweeney, John A.] Univ Texas Southwestern, Dept Psychiat, Dallas, TX 75390 USA. [Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Reilly, James] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Keedy, Sarah K.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM Judith.ford@ucsf.edu RI Keedy, Sarah/H-6557-2014; OI Keedy, Sarah/0000-0002-2139-9271; Roach, Brian/0000-0002-3264-1465 FU NIMH [MH077862, MH085485, MH058262] FX This work was supported by grants from NIMH MH077862, MH085485, and MH058262. We thank Brett Clementz for comments on an early draft. NR 62 TC 15 Z9 15 U1 3 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2014 VL 91 BP 91 EP 98 DI 10.1016/j.neuroimage.2014.01.003 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1VJ UT WOS:000338914100011 PM 24423729 ER PT J AU Huang, C Ackerman, JL Petibon, Y Normandin, MD Brady, TJ El Fakhri, G Ouyang, JS AF Huang, Chuan Ackerman, Jerome L. Petibon, Yoann Normandin, Marc D. Brady, Thomas J. El Fakhri, Georges Ouyang, Jinsong TI Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET-MR: Phantom and non-human primate studies SO NEUROIMAGE LA English DT Article DE Active marker; Brain PET; Simultaneous PET MR; Motion correction ID POSITRON-EMISSION-TOMOGRAPHY; HEAD MOTION; MAGNETIC-RESONANCE; LESION DETECTION; TRACKING SYSTEM; MONKEY BRAIN; RF COILS; RECEPTOR; ANESTHESIA; IMAGES AB Brain PET scanning plays an important role in the diagnosis, prognostication and monitoring of many brain diseases. Motion artifacts from head motion are one of the major hurdles in brain PET. In this work, we propose to use wireless MR active markers to track head motion in real time during a simultaneous PET MR brain scan and incorporate the motion measured by the markers in the listmode PET reconstruction. Several wireless MR active markers and a dedicated fast MR tracking pulse sequence module were built. Data were acquired on an ACR Flangeless PET phantom with multiple spheres and a non-human primate with and without motion. Motions of the phantom and monkey's head were measured with the wireless markers using a dedicated MR tracking sequence module. The motion PET data were reconstructed using list-mode reconstruction with and without motion correction. Static reference was used as gold standard for quantitative analysis. The motion artifacts, which were prominent on the images without motion correction, were eliminated by the wireless marker based motion correction in both the phantom and monkey experiments. Quantitative analysis was performed on the phantom motion data from 24 independent noise realizations. The reduction of bias of sphere-to-background PET contrast by active marker based motion correction ranges from 26% to 64% and 17% to 25% for hot (i.e., radioactive) and cold (i.e., non-radioactive) spheres, respectively. The motion correction improved the channelized Hotelling observer signal-to-noise ratio of the spheres by 1.2 to 6.9 depending on their locations and sizes. The proposed wireless MR active marker based motion correction technique removes the motion artifacts in the reconstructed PET images and yields accurate quantitative values. (C) 2014 Elsevier Inc. All rights reserved. C1 [Huang, Chuan; Petibon, Yoann; Normandin, Marc D.; Brady, Thomas J.; El Fakhri, Georges; Ouyang, Jinsong] Massachusetts Gen Hosp, Dept Imaging, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Huang, Chuan; Ackerman, Jerome L.; Normandin, Marc D.; Brady, Thomas J.; El Fakhri, Georges; Ouyang, Jinsong] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ackerman, Jerome L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Petibon, Yoann] Univ Paris 06, INSERM, UMRS 678, CHU Pitie Salpetriere,Lab Imagerie Fonct, Paris, France. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, 55 Fruit St,White Bldg 427, Boston, MA 02114 USA. EM huang.chuan@mgh.harvard.edu; jerry@nmr.mgh.harvard.edu; petibon@pet.mgh.harvard.edu; normandin.marc@mgh.harvard.edu; tom@nmr.mgh.harvard.edu; elfakhri@pet.mgh.harvard.edu; ouyang.jinsong@mgh.harvard.edu RI Normandin, Marc/C-6728-2015; Ackerman, Jerome/E-2646-2015; OI Normandin, Marc/0000-0003-1645-523X; Ackerman, Jerome/0000-0001-5176-7496; Huang, Chuan/0000-0001-6052-0663 FU National Institutes of Health (NIH) [R21-EB012326, R01-CA165221, R01-MH100350]; Athinoula A. Martinos Center for Biomedical Imaging; Center for Functional Neuroimaging Technologies - NIH [P41-EB015896] FX This research was supported in part by the National Institutes of Health (NIH) grants R21-EB012326, R01-CA165221, and R01-MH100350, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Functional Neuroimaging Technologies (funded by NIH grant P41-EB015896). NR 48 TC 9 Z9 9 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2014 VL 91 BP 129 EP 137 DI 10.1016/j.neuroimage.2013.12.061 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1VJ UT WOS:000338914100015 PM 24418501 ER PT J AU Chang, WT Setsompop, K Ahveninen, J Belliveau, JW Witzel, T Lin, FH AF Chang, Wei-Tang Setsompop, Kawin Ahveninen, Jyrki Belliveau, John W. Witzel, Thomas Lin, Fa-Hsuan TI Improving the spatial resolution of magnetic resonance inverse imaging via the blipped-CAIPI acquisition scheme SO NEUROIMAGE LA English DT Article DE Inverse imaging; Parallel imaging; Blip; CAIPIRINHA ID SURFACE-BASED ANALYSIS; FUNCTIONAL MRI; PHYSIOLOGICAL NOISE; GRANGER CAUSALITY; 1.5 T; FMRI; TIME; SENSITIVITY; RECONSTRUCTION; OXYGENATION AB Using simultaneous acquisition from multiple channels of a radio-frequency (RF) coil array, magnetic resonance inverse imaging (InI) achieves functional MRI acquisitions at a rate of 100 ms per whole-brain volume. ml accelerates the scan by leaving out partition encoding steps and reconstructs images by solving under-determined inverse problems using RF coil sensitivity information. Hence, the correlated spatial information available in the coil array causes spatial blurring in the InI reconstruction. Here, we propose a method that employs gradient blips in the partition encoding direction during the acquisition to provide extra spatial encoding in order to better differentiate signals from different partitions. According to our simulations, this blipped-Inl (bin') method can increase the average spatial resolution by 15.1% (1.3 mm) across the whole brain and from 32.6% (4.2 mm) in subcortical regions, as compared to the Inl method. In a visual fMRI experiment, we demonstrate that, compared to InI, the spatial distribution of bInI BOLD response is more consistent with that of a conventional echo-planar imaging (EPI) at the level of individual subjects. With the improved spatial resolution, especially in subcortical regions, blnl can be a useful fMRI tool for obtaining high spatiotemporal information for clinical and cognitive neuroscience studies. (C) 2013 Elsevier Inc. All rights reserved. C1 [Chang, Wei-Tang; Setsompop, Kawin; Ahveninen, Jyrki; Belliveau, John W.; Witzel, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Chang, Wei-Tang; Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. [Belliveau, John W.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Lin, FH (reprint author), Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. EM fhlin@ntu.edu.tw RI Witzel, Thomas/P-1402-2014; Setsompop, Kawin/P-1464-2014; Lin, Fa-Hsuan/G-6988-2012 OI Setsompop, Kawin/0000-0003-0455-7634; Lin, Fa-Hsuan/0000-0002-9539-1731 FU National Institutes of Health (NIH) [RO1DA14178, R01MH083744, R21DC010060, RO1HD040712, R01NS037462, P41 RR14075, R01 EB006847, RO1EB000790, R21EB007298]; Mental Illness and Neuroscience Discovery Institute (MIND) [NSC 101-2628-B-002-005-MY3]; National Science Council, Taiwan [NSC NSC 100-2325-B-002-046]; NIH/National Center for Research Resources Shared Instrumentation [S10RR014978, SlORR021110, S1ORR019307, S10RR023401]; Finnish Foundation for Technology Promotion FX We appreciate the technical support by Mary T. O'Hara and Lawrence T. White at Athinoula A. Martinos Center for Biomedical Imaging. This work was supported in part by Stephanie Rossi. Additionally, this work was supported by the National Institutes of Health (NIH) Grants RO1DA14178, R01MH083744, R21DC010060, RO1HD040712, R01NS037462, P41 RR14075, R01 EB006847, RO1EB000790, and R21EB007298, the Mental Illness and Neuroscience Discovery Institute (MIND), NSC 101-2628-B-002-005-MY3 (National Science Council, Taiwan), NSC NSC 100-2325-B-002-046 (National Science Council, Taiwan), NHRI-EX102-10247EI (National Health Research Institute, Taiwan), 100-EC-17-A-19-S1-175 (Ministry of Economic Affairs, Taiwan),and Academy of Finland (the FiDiPro program and grant 127624), Finnish Cultural Foundation, and Finnish Foundation for Technology Promotion. The research environment was supported by the NIH/National Center for Research Resources Shared Instrumentation Grants S10RR014978, SlORR021110, S1ORR019307, and S10RR023401. NR 57 TC 3 Z9 3 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 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2014 VL 91 BP 401 EP 411 DI 10.1016/j.neuroimage.2013.12.037 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1VJ UT WOS:000338914100041 PM 24374076 ER PT J AU Goldfarb, IT Sparks, TN Ortiz, VE Kaimal, A AF Goldfarb, Ilona T. Sparks, Teresa N. Ortiz, Vilma E. Kaimal, Anjali TI Association Between a Positive Screen on the STOP-BANG Obstructive Sleep Apnea Tool and Preeclampsia SO OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 62nd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY APR 26-30, 2014 CL Chicago, IL SP Amer Coll Obstetricians & Gynecologists C1 [Goldfarb, Ilona T.; Sparks, Teresa N.; Ortiz, Vilma E.; Kaimal, Anjali] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2014 VL 123 SU 1 BP 53S EP 53S PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AL4CG UT WOS:000339079900110 ER PT J AU Jung, HS Kim, KS Yun, SH Hahn, SK AF Jung, Ho Sang Kim, Ki Su Yun, Seok Hyun Hahn, Sei Kwang TI Enhancing the transdermal penetration of nanoconstructs: could hyaluronic acid be the key? SO NANOMEDICINE LA English DT Editorial Material DE hyaluronic acid; nanoconstructs; nanomedicines; transdermal delivery ID PHOTOTHERMAL ABLATION; DRUG-DELIVERY; SKIN; NANOPARTICLES; CONJUGATE; DISEASES; CANCER C1 [Jung, Ho Sang; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Kim, Ki Su; Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Yun, Seok Hyun] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, San 31, Pohang 790784, Kyungbuk, South Korea. EM skhanb@postech.ac.kr NR 18 TC 6 Z9 6 U1 1 U2 36 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD MAY PY 2014 VL 9 IS 6 BP 743 EP 745 DI 10.2217/NNM.14.47 PG 3 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA AK9XI UT WOS:000338781500001 PM 24981644 ER PT J AU Ngwa, W Kumar, R Sridhar, S Korideck, H Zygmanski, P Cormack, RA Berbeco, R Makrigiorgos, GM AF Ngwa, Wilfred Kumar, Rajiv Sridhar, Srinivas Korideck, Houari Zygmanski, Piotr Cormack, Robert A. Berbeco, Ross Makrigiorgos, G. Mike TI Targeted radiotherapy with gold nanoparticles: current status and future perspectives SO NANOMEDICINE LA English DT Review DE cancer; gold nanoparticle; nanomedicine; radiotherapy; retinal disease ID VASCULAR-DISRUPTING AGENTS; X-RAY-IRRADIATION; RECURRENT PROSTATE-CANCER; MONTE-CARLO-SIMULATION; VERTEPORFIN PHOTODYNAMIC THERAPY; DOSE-ESCALATION TRIAL; AMD 6-MONTH SAFETY; CELL LUNG-CANCER; RADIATION-THERAPY; MACULAR DEGENERATION AB Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed. C1 [Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas; Korideck, Houari; Zygmanski, Piotr; Cormack, Robert A.; Berbeco, Ross; Makrigiorgos, G. Mike] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas; Korideck, Houari; Zygmanski, Piotr; Cormack, Robert A.; Berbeco, Ross; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. EM mmakrigiorgos@lroc.harvard.edu FU Kayes Technology Research Awards; Mazonne Foundation; Joint Center for Radiation Therapy Foundation; DOD CDMRP [W81X-WH-12-1-0064]; NIH/NCI [R03 CA164645] FX The authors acknowledge funding support from the Kayes Technology Research Awards; Mazonne Foundation; Joint Center for Radiation Therapy Foundation; DOD CDMRP W81X-WH-12-1-0064; and NIH/NCI R03 CA164645. 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 172 TC 29 Z9 29 U1 7 U2 61 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD MAY PY 2014 VL 9 IS 7 BP 1063 EP 1082 DI 10.2217/NNM.14.55 PG 20 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA AK9YF UT WOS:000338783800017 PM 24978464 ER PT J AU Akeju, O Davis-Dusenbery, BN Cassel, SH Ichida, JK Eggan, K AF Akeju, Oluwaseun Davis-Dusenbery, Brandi N. Cassel, Seth H. Ichida, Justin K. Eggan, Kevin TI Ketamine exposure in early development impairs specification of the primary germ cell layers SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Mouse embryonic stem cells; NMDA; Ketamine; Neurogenesis; Mesoendoderm; Differentiation ID EMBRYONIC STEM-CELLS; ANTERIOR-POSTERIOR POLARITY; VISCERAL ENDODERM; MOTOR-NEURONS; MOUSE EMBRYO; SPONTANEOUS-ABORTION; NEURAL CONVERSION; DENTAL ASSISTANTS; GENE-EXPRESSION; NITROUS-OXIDE AB Preclinical and clinical evidence implicates N-methyl-D-aspartate receptor (NMDAr) signaling in early embryo-logical development. However, the role of NMDAr signaling in early development has not been well studied. Here, we use a mouse embryonic stem cell model to perform a step-wise exploration of the effects of NMDAr signaling on early cell fate specification. We found that antagonism of the NMDAr impaired specification into the neuroectodermal and mesoendodermal cell lineages, with little or no effect on specification of the extraembryonic endoderm cell lineage. Consistent with these findings, exogenous NMDA promoted neuroectodermal differentiation. Finally, NMDAr antagonism modified expression of several key targets of TGF-beta superfamily signaling, suggesting a mechanism for these findings. In summary, this study shows that NMDAr antagonism interferes with the normal developmental pathways of embryogenesis, and suggests that interference is most pronounced prior to neuroectodermal and mesoendodermal cell fate specification. (C) 2014 Elsevier Inc. All rights reserved. C1 [Akeju, Oluwaseun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Akeju, Oluwaseun; Davis-Dusenbery, Brandi N.; Cassel, Seth H.; Ichida, Justin K.; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Akeju, O (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM oluwaseun.akeju@mgh.harvard.edu FU Harvard Stem Cell Institute; Howard Hughes Medical Institute; National Institutes of Health [T32GM007592]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX We thank R. Kara and K. Baker for helpful comments on this manuscript. We also thank all past and present members of the Eggan laboratory for helpful discussions. This work was supported by the Harvard Stem Cell Institute, the Howard Hughes Medical Institute, the National Institutes of Health (T32GM007592), and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. NR 49 TC 4 Z9 4 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2014 VL 43 BP 59 EP 68 DI 10.1016/j.ntt.2014.04.001 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AK7QC UT WOS:000338621800009 PM 24746641 ER PT J AU Zhang, HJ Li, SG Li, HW AF Zhang, Haojian Li, Shaoguang Li, Huawei TI Management and orphan drug development for acute myeloid leukemia SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE acute myeloid leukemia; diagnosis; fms-related tyrosine kinase 3 tyrosine kinase inhibitors; heat shock protein 90 inhibitors; hypomethylating agents; immunotherapy prognosis ID ACUTE MYELOGENOUS LEUKEMIA; INTERNAL TANDEM DUPLICATION; FAVORABLE PROGNOSTIC-SIGNIFICANCE; DISEASE-STABILIZING TREATMENT; CONVENTIONAL CARE REGIMENS; TRANS-RETINOIC ACID; LOW-DOSE CYTARABINE; PHASE-III TRIAL; GEMTUZUMAB OZOGAMICIN; OLDER PATIENTS AB Introduction: Acute myeloid leukemia (AML) is a genetically heterogeneous disease with blocked differentiation of myeloid precursor cells. Genetic alterations have been identified in AML patients over the past several decades, which significantly improved the characterization and diagnosis of this disease. However, the therapeutic options for the treatment of AML are still limited. Areas covered: This review summarizes the diagnosis and prognosis of AML and current strategies for AML treatment. The new treatment agents that are in use and under development are focused on fms-related tyrosine kinase 3 tyrosine kinase inhibitors, heat shock protein 90 inhibitors, hypomethylating agents, immunotherapy of AML and other potential strategies. Expert opinion: Although the heterogeneity of AML significantly influences the outcomes in the treatment of AML patients, the application of high-throughput technology (such as next-generation sequencing), which helps to identify new genetic events and understand the molecular pathogenesis of AML, provides promise for developing new therapeutic strategies. These novel strategies will stimulate drug development and bring new hope to AML patients. However, seeking the combination of potential effective strategies with standard chemotherapy might be more feasible in the near future. C1 [Zhang, Haojian] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Li, Shaoguang; Li, Huawei] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Zhang, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Mayer Bldg,6 Floor,Room 640,450 Brookline Ave, Boston, MA 02215 USA. EM Haojian_Zhang@dfci.harvard.edu FU Leukemia & Lymphoma Society; National Institutes of Health [R01-CA122142, R01-CA114199] FX This work was supported by grants from the Leukemia & Lymphoma Society to H Zhang, and the National Institutes of Health (R01-CA122142, R01-CA114199) to S Li. The authors declare no conflict of interest and have received no payment in the preparation of this manuscript. NR 91 TC 0 Z9 0 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD MAY PY 2014 VL 2 IS 5 BP 441 EP 451 DI 10.1517/21678707.2014.891457 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK2WC UT WOS:000338279400002 ER PT J AU Savastru, D Chang, EW Miclos, S Pitman, MB Patel, A Iftimia, N AF Savastru, Dan Chang, Ernest W. Miclos, Sorin Pitman, Martha B. Patel, Ankit Iftimia, Nicusor TI Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical coherence tomography imaging; breast cancer; histopathology; positive margins ID REFLECTANCE SPECTROSCOPY; CONSERVING SURGERY; RAMAN-SPECTROSCOPY; CANCER; TISSUES; DIAGNOSIS; FLUORESCENCE; LUMPECTOMY; FEASIBILITY; HEMOGLOBIN AB This study aimed to evaluate the concept of using high-resolution optical coherence tomography (OCT) imaging to rapidly assess surgical specimens and determine if cancer positive margins were left behind in the surgical bed. A mouse model of breast cancer was used in this study. Surgical specimens from 30 animals were investigated with OCT and automated interpretation of the OCT images was performed and tested against histopathology findings. Specimens from 10 animals were used to build a training set of OCT images, while the remaining 20 specimens were used for a validation set of images. The validation study showed that automated interpretation of OCT images can differentiate tissue types and detect cancer positive margins with at least 81% sensitivity and 89% specificity. The findings of this pilot study suggest that OCT imaging of surgical specimens and automated interpretation of OCT data may enable in the future real-time feedback to the surgeon about margin status in patients with breast cancer, and potentially with other types of cancers. Currently, such feedback is not provided and if positive margins are left behind, patients have to undergo another surgical procedure. Therefore, this approach can have a potentially high impact on breast surgery outcome. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Savastru, Dan; Miclos, Sorin] Natl Inst Optoelect, RO-077125 Magurele, Ilfov, Romania. [Chang, Ernest W.; Patel, Ankit; Iftimia, Nicusor] Phys Sci Inc, Andover, MA 01810 USA. [Pitman, Martha B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.com FU Romanian government [184 PCCA/2012 - MOIST]; U.S. National Cancer Institute [5R42CA114896-04] FX This research program was funded in part by the Romanian government, Grant No. 184 PCCA/2012 - MOIST, and by U.S. National Cancer Institute, Grant No. 5R42CA114896-04. NR 42 TC 6 Z9 6 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2014 VL 19 IS 5 AR 056001 DI 10.1117/1.JBO.19.5.056001 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AK3OR UT WOS:000338334600018 PM 24788370 ER PT J AU Horn, DM Koplan, KE Senese, MD Orav, EJ Sequist, TD AF Horn, Daniel M. Koplan, Kate E. Senese, Margaret D. Orav, E. John Sequist, Thomas D. TI The Impact of Cost Displays on Primary Care Physician Laboratory Test Ordering SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE electronic health records; efficiency; health care costs; primary care ID OF-POCKET COSTS; HEALTH INFORMATION-TECHNOLOGY; DIAGNOSTIC-TESTS; CONTROLLED-TRIAL; PATIENT; QUALITY; COMMUNICATION; INTERVENTION; CLINICIAN; BEHAVIOR AB BACKGROUND: Physicians are under increased pressure to help control rising health care costs, though they lack information regarding cost implications of patient care decisions. OBJECTIVE: To evaluate the impact of real-time display of laboratory costs on primary care physician ordering of common laboratory tests in the outpatient setting. DESIGN: Interrupted time series analysis with a parallel control group. PARTICIPANTS: Two hundred and fifteen primary care physicians (153 intervention and 62 control) using a common electronic health record between April 2010 and November 2011. The setting was an alliance of five multispecialty group practices in Massachusetts. INTERVENTION: The average Medicare reimbursement rate for 27 laboratory tests was displayed within an electronic health record at the time of ordering, including 21 lower cost tests (< $40.00) and six higher cost tests (> $40.00). MAIN MEASURES: We compared the change-in-slope of the monthly laboratory ordering rate between intervention and control physicians for 12 months pre-intervention and 6 months post-intervention. We surveyed all intervention and control physicians at 6 months post-intervention to assess attitudes regarding costs and cost displays. KEY RESULTS: Among 27 laboratory tests, intervention physicians demonstrated a significant decrease in ordering rates compared to control physicians for five (19 %) tests. This included a significant relative decrease in ordering rates for four of 21 (19 %) lower cost laboratory tests and one of six (17 %) higher cost laboratory tests. A majority (81 %) of physicians reported that the intervention improved their knowledge of the relative costs of laboratory tests. CONCLUSIONS: Real-time display of cost information in an electronic health record can lead to a modest reduction in ordering of laboratory tests, and is well received. Our study demonstrates that electronic health records can serve as a tool to promote cost transparency and reduce laboratory test use. C1 [Horn, Daniel M.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Koplan, Kate E.; Senese, Margaret D.; Sequist, Thomas D.] Harvard Vanguard Med Associates, Newton, MA USA. [Koplan, Kate E.; Senese, Margaret D.; Sequist, Thomas D.] Atrius Hlth, Newton, MA USA. [Orav, E. John; Sequist, Thomas D.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02120 USA. [Sequist, Thomas D.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Sequist, TD (reprint author), Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St, Boston, MA 02120 USA. EM tsequist@partners.org NR 33 TC 27 Z9 27 U1 0 U2 7 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 MAY PY 2014 VL 29 IS 5 BP 708 EP 714 DI 10.1007/s11606-013-2672-1 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VL UT WOS:000338205700010 PM 24257964 ER PT J AU Restuccia, JD Mohr, D Meterko, M Stolzmann, K Kaboli, P AF Restuccia, Joseph D. Mohr, David Meterko, Mark Stolzmann, Kelly Kaboli, Peter TI The Association of Hospital Characteristics and Quality Improvement Activities in Inpatient Medical Services SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality improvement; hospital medicine; inpatient medicine; veterans ID HEALTH-CARE; OF-CARE; US HOSPITALS; INFORMATION-TECHNOLOGY; PATIENT OUTCOMES; IMPLEMENTATION; STRATEGIES; EFFICIENCY; ERR AB BACKGROUND: Quality of U. S. health care has been the focus of increasing attention, with deficiencies in patient care well recognized and documented. However, relatively little is known about the extent to which hospitals engage in quality improvement activities (QIAs) or factors influencing extent of QIAs. OBJECTIVE: To identify 1) the extent of QIAs in Veterans Administration (VA) inpatient medical services; and 2) factors associated with widespread adoption of QIAs, in particular use of hospitalists, non-physician providers, and extent of goal alignment between the inpatient service and senior managers on commitment to quality. DESIGN: Cross-sectional, descriptive study of QIAs using a survey administered to Chiefs of Medicine (COM) at all 124 VA acute care hospitals. We conducted hierarchical regression, regressing QIA use on facility contextual variables, followed by use of hospitalists, non-physician providers, and goal alignment/quality commitment. MAIN MEASURES: Outcome measures pertained to use of a set of 27 QIAs and to three dimensions-infrastructure, prevention, and information gathering-that were identified by factor analysis among the 27 QIAs overall. KEY RESULTS: Survey response rate was 90 % (111/124). Goal alignment/quality commitment was associated with more widespread use of all four QIA categories [ infrastructure (b=0.42; p<0.001); prevention (b=0.24; p<0.001); information gathering (b=0.28; p=<0.001); and overall QIA (b=0.31; p<0.001)], as was greater use of hospitalists [ infrastructure (b=0.55; p=0.03); prevention (b=0.61; p<0.001); information gathering (b=0.75; p=0.01); and overall QIAs (b=0.61; p<0.001)]; higher occupancy rate was associated with greater infrastructure QIAs (b=1.05, p=0.02). Non-physician provider use, hospital size, university affiliation, and geographic region were not associated with QIAs. CONCLUSION: As hospitals respond to changes in healthcare (e. g., pay for performance, accountable care organizations), this study suggests that practices such as use of hospitalists and leadership focus on goal alignment/quality commitment may lead to greater implementation of QIAs. C1 [Restuccia, Joseph D.; Mohr, David; Meterko, Mark; Stolzmann, Kelly] Boston VA Healthcare Syst, COLMR, Boston, MA USA. [Restuccia, Joseph D.] Boston Univ, Sch Management, Boston, MA 02215 USA. [Meterko, Mark] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Kaboli, Peter] Iowa City VA Healthcare Syst, Comprehens Access & Delivery Res & Evaluat CADRE, Iowa City, IA USA. [Kaboli, Peter] Univ Iowa, Dept Internal Med, Carver Coll Med, Div Gen Internal Med, Iowa City, IA 52242 USA. RP Restuccia, JD (reprint author), Boston VA Healthcare Syst, COLMR, Boston, MA USA. EM jres@bu.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [REA 09-220]; Comprehensive Access & Delivery Research and Evaluation (CADRE) Center at the Iowa City VAMC [HFP 04-149]; Center for Organizational Leadership and Management Research (COLMR) at the Boston VA Healthcare System [HFP 04-145] FX The work reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (REA 09-220), and the Comprehensive Access & Delivery Research and Evaluation (CADRE) Center at the Iowa City VAMC (HFP 04-149) and the Center for Organizational Leadership and Management Research (COLMR) at the Boston VA Healthcare System (HFP 04-145). We acknowledge and appreciate the intellectual contribution made by Dr. Alan Cohen, Dr. Michael Shwartz and Jed Horwitt who, along with Dr. Restuccia, developed the Quality Improvement Activities Survey from which many of the questions in our survey were drawn. We also wish to thank Dr. Caitlin Brennan and Dr. James Burgess for their careful review of the manuscript and insightful comments. Views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 50 TC 3 Z9 3 U1 13 U2 25 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 MAY PY 2014 VL 29 IS 5 BP 715 EP 722 DI 10.1007/s11606-013-2759-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VL UT WOS:000338205700011 PM 24424776 ER PT J AU Johnson, HM Thorpe, CT Bartels, CM Schumacher, JR Palta, M Pandhi, N Sheehy, AM Smith, MA AF Johnson, Heather M. Thorpe, Carolyn T. Bartels, Christie M. Schumacher, Jessica R. Palta, Mari Pandhi, Nancy Sheehy, Ann M. Smith, Maureen A. TI Antihypertensive Medication Initiation Among Young Adults with Regular Primary Care Use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypertension; ambulatory care; disease management ID BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR-DISEASE; HYPERTENSION TREATMENT; ADMINISTRATIVE DATA; DRUG-THERAPY; RISK-FACTORS; IMPACT; COMORBIDITIES; OPPORTUNITIES AB BACKGROUND: Young adults with hypertension have the lowest prevalence of controlled blood pressure compared to middle-aged and older adults. Uncontrolled hypertension, even among young adults, increases future cardiovascular event risk. However, antihypertensive medication initiation is poorly understood among young adults and may be an important intervention point for this group. OBJECTIVE: The purpose of this study was to compare rates and predictors of antihypertensive medication initiation between young adults and middle-aged and older adults with incident hypertension and regular primary care contact. DESIGN: A retrospective analysis PARTICIPANTS: Adults >= 18 years old (n=10,022) with incident hypertension and no prior antihypertensive prescription, who received primary care at a large, Midwestern, academic practice from 2008-2011. MAIN MEASURES: The primary outcome was time from date of meeting hypertension criteria to antihypertensive medication initiation, or blood pressure normalization without medication. Kaplan-Meier analysis was used to estimate the probability of antihypertensive medication initiation over time. Cox proportional-hazard models (HR; 95 % CI) were fit to identify predictors of delays in medication initiation, with a subsequent subpopulation analysis for young adults (18-39 years old). KEY RESULTS: After a mean follow-up of 20 (+/- 13) months, 34 % of 18-39 year-olds with hypertension met the endpoint, compared to 44 % of 40-59 year-olds and 56 % of >= 60 year-olds. Adjusting for patient and provider factors, 18-39 year-olds had a 44 % slower rate of medication initiation (HR 0.56; 0.47-0.67) than >= 60 year-olds. Among young adults, males, patients with mild hypertension, and White patients had a slower rate of medication initiation. Young adults with Medicaid and more clinic visits had faster rates. CONCLUSIONS: Even with regular primary care contact and continued elevated blood pressure, young adults had slower rates of antihypertensive medication initiation than middle-aged and older adults. Interventions are needed to address multifactorial barriers contributing to poor hypertension control among young adults. C1 [Johnson, Heather M.; Bartels, Christie M.; Sheehy, Ann M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Johnson, Heather M.; Bartels, Christie M.; Schumacher, Jessica R.; Pandhi, Nancy; Sheehy, Ann M.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Madison, WI 53792 USA. [Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Schumacher, Jessica R.; Palta, Mari; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53792 USA. [Palta, Mari] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI 53792 USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Johnson, Heather M.] Univ Wisconsin, Sch Med & Publ Hlth, Div Cardiovasc Med, Madison, WI 53792 USA. RP Johnson, HM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Div Cardiovasc Med, H4-512 CSC,MC 3248,600 Highland Ave, Madison, WI 53792 USA. EM hm2@medicine.wisc.edu OI Johnson, Heather/0000-0002-4916-3519 FU Clinical and Translational Science Award (CTSA) program [UL1RR025011]; National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health [U54TR000021]; National Heart, Lung, and Blood Institute of the National Institutes of Health [K23HL112907]; University of Wisconsin Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [K23AR062381]; National Institute on Aging of the National Institutes of Health [K08AG029527]; University of Wisconsin Health Innovation Program; University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program FX Research reported in this manuscript was supported by the Clinical and Translational Science Award (CTSA) program, previously through the National Center for Research Resources (NCRR) under award number UL1RR025011, and now by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health under award number U54TR000021. Heather Johnson is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL112907, and also by the University of Wisconsin Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health. Christie Bartels is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR062381. Nancy Pandhi is supported by the National Institute on Aging of the National Institutes of Health under award number K08AG029527. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Additional funding for this project was provided by the University of Wisconsin Health Innovation Program and the University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program. NR 42 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2014 VL 29 IS 5 BP 723 EP 731 DI 10.1007/s11606-014-2790-4 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VL UT WOS:000338205700012 PM 24493322 ER PT J AU Sen, AP Sewell, TB Riley, EB Stearman, B Bellamy, SL Hu, MF Tao, YY Zhu, JS Park, JD Loewenstein, G Asch, DA Volpp, KG AF Sen, Aditi P. Sewell, Taylor B. Riley, E. Brooks Stearman, Beth Bellamy, Scarlett L. Hu, Michelle F. Tao, Yuanyuan Zhu, Jingsan Park, James D. Loewenstein, George Asch, David A. Volpp, Kevin G. TI Financial Incentives for Home-Based Health Monitoring: A Randomized Controlled Trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic disease; health information technology; health behavior; disease management; adherence ID IMPROVE WARFARIN ADHERENCE; LONGITUDINAL DATA-ANALYSIS; DIABETIC-PATIENTS; HEART-FAILURE; BLOOD-GLUCOSE; WEIGHT-LOSS; LOTTERY; INSULIN; REWARD; REGRET AB BACKGROUND: Home wireless device monitoring could play an important role in improving the health of patients with poorly controlled chronic diseases, but daily engagement rates among these patients may be low. OBJECTIVE: To test the effectiveness of two different magnitudes of financial incentives for improving adherence to remote-monitoring regimens among patients with poorly controlled diabetes. DESIGN: Randomized, controlled trial. (Clinicaltrials.govIdentifier: NCT01282957). PARTICIPANTS: Seventy-five patients with a hemoglobin A1c greater than or equal to 7.5 % recruited from a Primary Care Medical Home practice at the University of Pennsylvania Health System. INTERVENTIONS: Twelve weeks of daily home-monitoring of blood glucose, blood pressure, and weight (control group; n=28); a lottery incentive with expected daily value of $2.80 (n=26) for daily monitoring; and a lottery incentive with expected daily value of $1.40 (n=21) for daily monitoring. MAIN MEASURES: Daily use of three home-monitoring devices during the three-month intervention (primary outcome) and during the three-month follow-up period and change in A1c over the intervention period (secondary outcomes). KEY RESULTS: Incentive arm participants used devices on a higher proportion of days relative to control (81 % low incentive vs. 58 %, P=0.007; 77 % high incentive vs. 58 %, P=0.02) during the three-month intervention period. There was no difference in adherence between the two incentive arms (P=0.58). When incentives were removed, adherence in the high incentive arm declined while remaining relatively high in the low incentive arm. In month 6, the low incentive arm had an adherence rate of 62 % compared to 35 % in the high incentive arm (P=0.015) and 27 % in the control group (P=0.002). CONCLUSIONS: A daily lottery incentive worth $1.40 per day improved monitoring rates relative to control and had significantly better efficacy once incentives were removed than a higher incentive. C1 [Sen, Aditi P.; Stearman, Beth; Tao, Yuanyuan; Zhu, Jingsan; Loewenstein, George; Asch, David A.; Volpp, Kevin G.] Penn CMU Roybal P30 Ctr Behav Econ & Hlth, Philadelphia, PA USA. [Sen, Aditi P.; Stearman, Beth; Tao, Yuanyuan; Zhu, Jingsan; Loewenstein, George; Asch, David A.; Volpp, Kevin G.] Leonard Davis Inst Ctr Hlth Incent & Behav Econ, Philadelphia, PA USA. [Sen, Aditi P.; Sewell, Taylor B.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Sewell, Taylor B.; Riley, E. Brooks; Hu, Michelle F.; Tao, Yuanyuan; Zhu, Jingsan; Park, James D.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Stearman, Beth] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Bellamy, Scarlett L.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Park, James D.] Rutgers, Robert Wood Johnson Med Sch, Camden, NJ USA. [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Sen, AP (reprint author), Univ Penn, Wharton Sch, Dept Hlth Care Management, 3461 Locust Walk, Philadelphia, PA 19104 USA. EM Aditisen@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU National Institute on Aging [RC2AG036592, P30AG034546] FX This work was supported by grants RC2AG036592 and P30AG034546 from the National Institute on Aging. NR 26 TC 12 Z9 12 U1 3 U2 17 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 MAY PY 2014 VL 29 IS 5 BP 770 EP 777 DI 10.1007/s11606-014-2778-0 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VL UT WOS:000338205700018 PM 24522623 ER PT J AU Yano, EM AF Yano, Elizabeth M. TI Teaching Commentary on "A Primary Care-Based Multidisciplinary Readmission Prevention Program": Essential Aspects of Comparability and Context in Practice-Based Program Evaluation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID HEALTH-CARE; IMPLEMENTATION; SCIENCE C1 [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Sepulveda, CA 91343 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM Elizabeth.yano@va.gov NR 22 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2014 VL 29 IS 5 BP 805 EP 807 DI 10.1007/s11606-014-2820-2 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VL UT WOS:000338205700026 PM 24627269 ER PT J AU Chiovaro, J Douglas, V Gaggar, A Dhaliwal, G AF Chiovaro, Joseph Douglas, Vanja Gaggar, Anuj Dhaliwal, Gurpreet TI Exhausting the Differential SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE cerebral aneurysms; motor weakness; dyspnea ID PROBLEM REPRESENTATION; MYASTHENIA-GRAVIS; SIGN-OUT; STRATEGIES; RECOMMENDATIONS; QUALITY; CARE C1 [Chiovaro, Joseph] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Chiovaro, Joseph] Portland VA Med Ctr, Portland, OR USA. [Douglas, Vanja] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Gaggar, Anuj; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chiovaro, J (reprint author), P3 Med Portland VA Med Ctr, Dept Med, 3710 Southwest US Vet Hosp Rd, Portland, OR 97239 USA. EM jchiovaro@gmail.com NR 13 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2014 VL 29 IS 5 BP 808 EP 812 DI 10.1007/s11606-013-2730-8 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VL UT WOS:000338205700027 PM 24395100 ER PT J AU Rhee, C Moradi, H Brunelli, S Jing, JN Nakata, T Nguyen, D Kovesdy, C Brent, G Kalantar-Zadeh, K AF Rhee, Connie Moradi, Hamid Brunelli, Steven Jing, Jennie Nakata, Tracy Danh, Nguyen Kovesdy, Csaba Brent, Gregory Kalantar-Zadeh, Kamyar TI ASSOCIATION BETWEEN ADIPONECTIN AND MORTALITY IN HEMODIALYSIS PATIENTS FROM THE MADRAD STUDY SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 51st Congress of the European-Renal-Association(ERA)/European-Dialysis-and-Transplant-Associa tion (EDTA) CY MAY 31-JUN 03, 2014 CL Amsterdam, NETHERLANDS SP European Renal Assoc, European Dialysis & Transplant Assoc C1 [Rhee, Connie; Moradi, Hamid; Jing, Jennie; Nakata, Tracy; Danh, Nguyen; Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Orange, CA 92668 USA. [Brunelli, Steven] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kovesdy, Csaba] Memphis VA Med Ctr, Memphis, TN USA. [Brent, Gregory] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2014 VL 29 SU 3 MA SP604 BP 274 EP 274 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AJ9FQ UT WOS:000338013501083 ER PT J AU Hutter, M AF Hutter, Matthew TI Why readmissions matter .... SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Metabolic-and-Bariatric-Surgery (ASMBS) CY NOV 16, 2013 CL Atlanta, GA SP Amer Soc Metab & Bariatr Surg C1 Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Hutter, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, 15 Parkman St,Wang 460, Boston, MA 02114 USA. EM mhutter@partners.org NR 3 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 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAY-JUN PY 2014 VL 10 IS 3 BP 379 EP 381 DI 10.1016/j.soard.2014.02.031 PG 3 WC Surgery SC Surgery GA AK1KX UT WOS:000338175100002 PM 24951059 ER PT J AU Sogg, S Stoeckel, L AF Sogg, Stephanie Stoeckel, Luke TI Comment on: High-risk alcohol use after weight loss surgery SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material ID BYPASS INCREASES ETHANOL; CONSUMPTION; RATS C1 [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie; Stoeckel, Luke] Harvard Univ, Sch Med, Boston, MA USA. [Stoeckel, Luke] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sogg, S (reprint author), Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAY-JUN PY 2014 VL 10 IS 3 BP 513 EP 515 PG 3 WC Surgery SC Surgery GA AK1KX UT WOS:000338175100034 PM 24794185 ER PT J AU Vistamehr, A Kautz, SA Neptune, RR AF Vistamehr, Arian Kautz, Steven A. Neptune, Richard R. TI The influence of solid ankle-foot-orthoses on forward propulsion and dynamic balance in healthy adults during walking SO CLINICAL BIOMECHANICS LA English DT Article DE Gait; Orthotic; AFO; Angular momentum; Biomechanics ID PLANE ANGULAR-MOMENTUM; HEMIPARETIC PATIENTS; MUSCLE CONTRIBUTIONS; HEMIPLEGIC PATIENTS; FRONTAL-PLANE; PUSH-OFF; GAIT; BODY; PROGRESSION; SUPPORT AB Background: In post-stroke hemiparetic subjects, solid polypropylene ankle-foot-orthoses are commonly prescribed to assist in foot clearance during swing while bracing the ankle during stance. Mobility demands, such as changing walking speed and direction, are accomplished by accelerating or decelerating the body and maintaining dynamic balance. Previous studies have shown that the ankle plantarflexors are primary contributors to these essential biomechanical functions. Thus, with ankle-foot-orthoses limiting ankle motion and plantarflexor output during stance, execution of these walking subtasks may be compromised. This study examined the influence of a solid polypropylene ankle-foot-orthosis on forward propulsion and dynamic balance in healthy adults. Methods: Kinematic and kinetic data were recorded from 10 healthy adults walking with and without a unilateral ankle-foot-orthosis at steady-state slow (0.6 m/s) and moderate (1.2 m/s) speeds, and during accelerated (0-1.8 m/s at 0.06 m/s(2)) and decelerated (1.8-0 m/s at - 0.06 m/s(2)) walking. Propulsion was quantified by propulsive and braking impulses (i.e., time integral of the anterior-posterior ground reaction force) while dynamic balance was quantified by the peak-to-peak range of whole-body angular momentum. Findings: The propulsive impulses decreased in the leg with ankle-foot-orthosis compared to the contralateral leg and no ankle-foot-orthosis condition. Further, the ankle-foot-orthosis resulted in a greater range of angular momentum in both the frontal and sagittal planes, which were correlated with the reduced peak hip abduction and reduced ankle plantarflexor moments, respectively. Interpretation: Solid ankle-foot-orthoses limit the successful execution of important mobility subtasks in healthy adults and that the prescription of ankle-foot-orthosis should be carefully considered. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Vistamehr, Arian; Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 204 E Dean Keeton St,Stop C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu OI Kautz, Steven/0000-0003-3151-8235 FU American Heart Association SouthWest Affiliate pre-doctoral fellowship [12PRE12030414]; Ralph H. Johnson VA Medical Center; Office of Research and Development, Rehabilitation Research and Development, U.S. Department of Veterans Affairs FX The authors are grateful to the members of the Locomotion Energetics and Assessment Lab in the Center for Rehabilitation Research in Neurological Conditions at the Medical University of South Carolina for their help with subject recruitment and data collection. This work was supported by an American Heart Association SouthWest Affiliate pre-doctoral fellowship (12PRE12030414) and supported in part by the Ralph H. Johnson VA Medical Center and the Office of Research and Development, Rehabilitation Research and Development, U.S. Department of Veterans Affairs. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the AHA or the VA. NR 35 TC 3 Z9 4 U1 6 U2 29 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD MAY PY 2014 VL 29 IS 5 BP 583 EP 589 DI 10.1016/j.clinbiomech.2014.02.007 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA AJ7MN UT WOS:000337880900017 PM 24698166 ER PT J AU Tonsho, M Michel, S Ahmed, Z Alessandrini, A Madsen, JC AF Tonsho, Makoto Michel, Sebastian Ahmed, Zain Alessandrini, Alessandro Madsen, Joren C. TI Heart Transplantation: Challenges Facing the Field SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; REGULATORY T-CELLS; ANTIBODY-MEDIATED REJECTION; TUBULAR EPITHELIAL-CELLS; PLASMACYTOID DENDRITIC CELLS; SINGLE-DONOR ALLOGRAFTS; HEPATIC STELLATE CELLS; KIDNEY GRAFT-SURVIVAL; MINIATURE SWINE; RENAL-ALLOGRAFTS AB There has been significant progress in the field of heart transplantation over the last 45 years. The 1-yr survival rates following heart transplantation have improved from 30% in the 1970s to almost 90% in the 2000s. However, there has been little change in long-term outcomes. This is mainly due to chronic rejection, malignancy, and the detrimental side effects of chronic immunosuppression. In addition, over the last decade, new challenges have arisen such as increasingly complicated recipients and antibody-mediated rejection. Most, if not all, of these obstacles to long-term survival could be prevented or ameliorated by the induction of transplant tolerance wherein the recipient's immune system is persuaded not to mount a damaging immune response against donor antigens, thus eliminating the need for chronic immunosuppression. However, the heart, as opposed to other allografts like kidneys, appears to be a tolerance-resistant organ. Understanding why organs like kidneys and livers are prone to tolerance induction, whereas others like hearts and lungs are tolerance-resistant, could aid in our attempts to achieve long-term, immunosuppression-free survival in human heart transplant recipients. It could also advance the field of pig-to-human xenotransplantation, which, if successful, would eliminate the organ shortage problem. Of course, there are alternative futures to the field of heart transplantation that may include the application of total mechanical support, stem cells, or bioengineered whole organs. Which modality will be the first to reach the ultimate goal of achieving unlimited, long-term, circulatory support with minimal risk to longevity or lifestyle is unknown, but significant progress in being made in each of these areas. C1 [Tonsho, Makoto; Ahmed, Zain; Alessandrini, Alessandro; Madsen, Joren C.] Massachusetts Gen Hosp, MGH Transplantat Ctr, Boston, MA 02114 USA. [Michel, Sebastian; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, MGH Transplantat Ctr, Boston, MA 02114 USA. EM jcmadsen@partners.org FU National Heart, Lung, and Blood Institute [P01HL18646]; National Institute of Allergy and Infectious Disease of the National Institutes of Health [U01AI94374, R01AI081734-01A1]; [C06RR020135-01] FX This work is supported in part by grants from the National Heart, Lung, and Blood Institute (P01HL18646) and the National Institute of Allergy and Infectious Disease (U01AI94374, R01AI081734-01A1) of the National Institutes of Health. We acknowledge C06RR020135-01 for construction of the facility used for production and maintenance of miniature swine and are indebted to J. Scott Arn for herd management and quality-control typing. NR 137 TC 3 Z9 3 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD MAY PY 2014 VL 4 IS 5 AR a015636 DI 10.1101/cshperspect.a015636 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AJ9HV UT WOS:000338020100004 ER PT J AU Magidson, JF Roberts, BW Collado-Rodriguez, A Lejuez, CW AF Magidson, Jessica F. Roberts, Brent W. Collado-Rodriguez, Anahi Lejuez, C. W. TI Theory-Driven Intervention for Changing Personality: Expectancy Value Theory, Behavioral Activation, and Conscientiousness SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE conscientiousness; expectancy value theory; behavioral activation; bottom-up approach to personality change ID ELEVATED DEPRESSIVE SYMPTOMS; PLACEBO-CONTROLLED-TRIAL; ACHIEVEMENT-MOTIVATION; HEALTH-STATUS; SUBSTANCE USE; TRAITS; METAANALYSIS; PERFORMANCE; OUTCOMES; DISORDER AB Considerable evidence suggests that personality traits may be changeable, raising the possibility that personality traits most linked to health problems can be modified with intervention. A growing body of research suggests that problematic personality traits may be altered with behavioral intervention using a bottom-up approach. That is, by targeting core behaviors that underlie personality traits with the goal of engendering new, healthier patterns of behavior that, over time, become automatized and manifest in changes in personality traits. Nevertheless, a bottom-up model for changing personality traits is somewhat diffuse and requires clearer integration of theory and relevant interventions to enable real clinical application. As such, this article proposes a set of guiding principles for theory-driven modification of targeted personality traits using a bottom-up approach, focusing specifically on targeting the trait of conscientiousness using a relevant behavioral intervention, Behavioral Activation (BA), considered within the motivational framework of expectancy value theory (EVT). We conclude with a real case example of the application of BA to alter behaviors counter to conscientiousness in a substance-dependent patient, highlighting the EVT principles most relevant to the approach and the importance and viability of a theoretically driven, bottom-up approach to changing personality traits. C1 [Magidson, Jessica F.; Collado-Rodriguez, Anahi; Lejuez, C. W.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Magidson, Jessica F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Roberts, Brent W.] Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. RP Magidson, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM jmagidson@partners.org FU NIDA NIH HHS [T32 DA028855, F31 DA026679, R01 DA019405] NR 74 TC 31 Z9 31 U1 4 U2 28 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 EI 1939-0599 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2014 VL 50 IS 5 BP 1442 EP 1450 DI 10.1037/a0030583 PG 9 WC Psychology, Developmental SC Psychology GA AJ7TR UT WOS:000337901000010 PM 23106844 ER PT J AU Davids, MS Brown, JR AF Davids, Matthew S. Brown, Jennifer R. TI Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase SO FUTURE ONCOLOGY LA English DT Article DE B-cell receptor; BTK; CLL; ibrutinib; kinase; lymphocytosis; MCL; NHL ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TARGETING BTK; OPEN-LABEL; IN-VIVO; PCI-32765; TRIAL; RITUXIMAB; BENDAMUSTINE; MULTICENTER; SURVIVAL AB Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenstrom's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies. C1 [Davids, Matthew S.; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Chron Lymphocyt Leukemia Ctr, Boston, MA 02115 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Chron Lymphocyt Leukemia Ctr, Boston, MA 02115 USA. EM jennifer_brown@dfci.harvard.edu FU Bristol-Myers Squibb; Sanofi-Aventis FX MS Davids has served as a consultant for Infinity, and has received research funding from Bristol-Myers Squibb. JR Brown has served as a consultant for Avila, Novartis, Genentech, Celgene, Emergent, Sanofi-Aventis, Pharmacyclics and Onyx, and has received research funding from Genzyme (now Sanofi-Aventis). 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 31 TC 20 Z9 21 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD MAY PY 2014 VL 10 IS 6 BP 957 EP 967 DI 10.2217/fon.14.51 PG 11 WC Oncology SC Oncology GA AJ8FO UT WOS:000337938300011 PM 24941982 ER PT J AU Duska, LR Dizon, DS AF Duska, Linda R. Dizon, Don S. TI Improving quality of life in female cancer survivors: current status and future questions SO FUTURE ONCOLOGY LA English DT Article DE cancer survivor; cancer treatment; intimacy; lifestyle; obesity; sexual health; survivorship care plan; survivorship clinic; survivorship medicine ID GYNECOLOGIC-ONCOLOGY-GROUP; SUPPORTIVE CARE NEEDS; BREAST-CANCER; OVARIAN-CANCER; PELVIC RADIOTHERAPY; ENDOMETRIAL CANCER; SEXUAL FUNCTION; CLINICAL-TRIAL; GASTROINTESTINAL SYMPTOMS; VAGINAL BRACHYTHERAPY AB Almost 14 million people in the USA alone have been diagnosed with cancer. Given the improvements in diagnosis and treatment, over 60% of patients are expected to survive 5 years or more from the point of diagnosis. Treatments for cancer may result in long-term issues including those that impact the physical, emotional, spiritual or social domains. However, how best to care for issues in survivors remains unclear. Although much attention has been focused on survivorship care plans and survivorship clinics, there are limited data to show they improve outcomes. This article reviews the issues in female cancer survivors that can occur following diagnosis and treatment and suggest strategies that may assist in management. Finally, we review the current views regarding the care of cancer survivors and suggest important issues that must be addressed so that we can reach our goal of improvement in the quality of life of this emerging population. C1 [Duska, Linda R.] Univ Virginia, Dept Obstet Gynecol, Div Gynecol Oncol, Charlottesville, VA USA. [Dizon, Don S.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. EM ddizon@partners.org NR 77 TC 0 Z9 1 U1 1 U2 11 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD MAY PY 2014 VL 10 IS 6 BP 1015 EP 1026 DI 10.2217/fon.13.249 PG 12 WC Oncology SC Oncology GA AJ8FO UT WOS:000337938300017 PM 24941987 ER PT J AU Bowles, DW McDermott, JD Jimeno, A AF Bowles, Daniel W. McDermott, Jessica D. Jimeno, Antonio TI Novel treatments for head and neck squamous cell carcinoma: preclinical identification and clinical investigation SO FUTURE ONCOLOGY LA English DT Review DE c-MET; EGFR; head and neck squamous cell carcinoma; Hedgehog; human papillomavirus; immunotherapy; Notch; PI3K; tyrosine kinase inhibitors ID GROWTH-FACTOR RECEPTOR; EPITHELIAL-MESENCHYMAL TRANSITION; REGULATORY T-CELLS; PHASE-II TRIAL; HUMAN-PAPILLOMAVIRUS INFECTION; CHEMOTHERAPY PLUS CETUXIMAB; ADVANCED SOLID TUMORS; HPV-ASSOCIATED HEAD; OROPHARYNGEAL CANCER; C-MET AB Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide. Classically, it is a disease related to tobacco and alcohol use; an increasing number of patients are being diagnosed with HNSCC caused by infection with the human papillomavirus. New deep-sequencing techniques have confirmed the importance of p53 and EGF receptor in HNSCC development, and have identified pathways of critical importance, such as PI3K/mTOR and NOTCH. Increasing knowledge of key molecular features has lead to new therapeutic avenues for HNSCC. Novel therapies under investigation in HNSCC include antibody and small molecule inhibitors of EGF receptor and its family members, PI3K inhibitors, antiangiogenic agents, immunotherapies and agents interacting with early developmental pathways such as Hedgehog. C1 [Bowles, Daniel W.; McDermott, Jessica D.; Jimeno, Antonio] Univ Colorado, Div Med Oncol, Sch Med, Boulder, CO 80309 USA. [Bowles, Daniel W.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Denver, CO USA. RP Jimeno, A (reprint author), Univ Colorado, Div Med Oncol, Sch Med, Boulder, CO 80309 USA. EM antonio.jimeno@ucdenver.edu NR 161 TC 3 Z9 4 U1 1 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD MAY PY 2014 VL 10 IS 6 BP 1065 EP 1080 DI 10.2217/fon.14.18 PG 16 WC Oncology SC Oncology GA AJ8FO UT WOS:000337938300020 PM 24941990 ER PT J AU Reagan, JL Castillo, JJ AF Reagan, John L. Castillo, Jorge J. TI Ofatumumab as front-line therapy in untreated chronic lymphocytic leukemia SO FUTURE ONCOLOGY LA English DT Article DE chronic lymphocytic leukemia; immunotherapy; monoclonal antibodies; ofatumumab; untreated ID COMPLEMENT-DEPENDENT CYTOTOXICITY; MONOCLONAL-ANTIBODIES; PROGRESSION-FREE; CELL CLEARANCE; CD20 ANTIBODY; PHASE-II; IN-VITRO; RITUXIMAB; FLUDARABINE; LYMPHOMA AB Ofatumumab is a fully human IgG1 type I anti-CD20 monoclonal antibody that binds to both the small and large loop of the membrane antigen CD20. Much of its therapeutic efficacy is derived through complement-dependent cytotoxicity, although it also appears to operate via induction of caspase-dependent apoptosis and shows potent antibody-dependent cellular phagocytosis. CD20 is an important but sometimes difficult antigen to effectively target in chronic lymphocytic leukemia (CLL) secondary to its overall dim expression in CLL cells. Currently, ofatumumab is approved in the USA and EU for fludarabine- and alemtuzumab-refractory CLL patients. However, the experience with ofatumumab in untreated CLL patients is mounting and shows competitive response and survival rates with an acceptable adverse event profile. Herein, we outline the efficacy and toxicities of ofatumumab alone and in combination for the front-line treatment of CLL. C1 [Reagan, John L.] Rhode Isl Hosp, Div Hematol & Oncol, Providence, RI USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. RP Castillo, JJ (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 46 TC 5 Z9 4 U1 0 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD MAY PY 2014 VL 10 IS 7 BP 1147 EP 1155 DI 10.2217/fon.14.73 PG 9 WC Oncology SC Oncology GA AJ8IF UT WOS:000337946000011 PM 24947256 ER PT J AU Olsen, C Fleming, K Prendergast, N Rubio, R Emmert-Streib, F Bontempi, G Haibe-Kains, B Quackenbush, J AF Olsen, Catharina Fleming, Kathleen Prendergast, Niall Rubio, Renee Emmert-Streib, Frank Bontempi, Gianluca Haibe-Kains, Benjamin Quackenbush, John TI Inference and validation of predictive gene networks from biomedical literature and gene expression data SO GENOMICS LA English DT Article DE Network inference; Quantitative validation; Gene expression; Targeted perturbations ID INFERRING CELLULAR NETWORKS; REGULATORY NETWORKS; MICROARRAY DATA; PROFILES; LINES AB Although many methods have been developed for inference of biological networks, the validation of the resulting models has largely remained an unsolved problem. Here we present a framework for quantitative assessment of inferred gene interaction networks using knock-down data from cell line experiments. Using this framework we are able to show that network inference based on integration of prior knowledge derived from the biomedical literature with genomic data significantly improves the quality of inferred networks relative to other approaches. Our results also suggest that cell line experiments can be used to quantitatively assess the quality of networks inferred from tumor samples. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Olsen, Catharina; Bontempi, Gianluca] Univ Libre Brussels, Machine Learning Grp, Brussels, Belgium. [Olsen, Catharina; Bontempi, Gianluca] ULB VUB, Interuniv Inst Bioinformat Brussels, Brussels, Belgium. [Fleming, Kathleen; Prendergast, Niall; Rubio, Renee; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Computat Biol & Funct Genom Lab, Boston, MA 02115 USA. [Emmert-Streib, Frank] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Computat Biol & Machine Learning Lab, Belfast, Antrim, North Ireland. [Haibe-Kains, Benjamin] Univ Hlth Network, Princess Margaret Canc Ctr, Bioinformat & Computat Genom Lab, Toronto, ON, Canada. RP Haibe-Kains, B (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Bioinformat & Computat Genom Lab, Toronto, ON, Canada. EM bhaibeka@uhnresearch.ca; johnq@jimmy.harvard.edu RI Emmert-Streib, Frank/G-8099-2011; Haibe-Kains, Benjamin/D-3702-2011 OI Emmert-Streib, Frank/0000-0003-0745-5641; Haibe-Kains, Benjamin/0000-0002-7684-0079 FU National Library of Medicine of the US National Institutes of Health [1R01LM010129, R01LM010129]; Belgian French Community ARC (Action de Recherche Concertee) FX Funding for open access charge: National Library of Medicine of the US National Institutes of Health (grant 1R01LM010129). JQ, KF, NP and RR were supported by a grant from the National Library of Medicine of the US National Institutes of Health (R01LM010129). GB and CO were supported by the Belgian French Community ARC (Action de Recherche Concertee, Discovery of the molecular pathways regulating pancreatic beta cell dysfunction and apoptosis in diabetes using functional genomics and bioinformatics) funding. NR 33 TC 11 Z9 11 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD MAY-JUN PY 2014 VL 103 IS 5-6 BP 329 EP 336 DI 10.1016/j.ygeno.2014.03.004 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AJ9AY UT WOS:000338000400003 PM 24691108 ER PT J AU Suhler, EB Lim, LL Beardsley, RM Giles, TR Pasadhilka, S Lee, ST Saint Sardos, AD Butler, NJ Smith, JR Rosenbaum, JT AF Suhler, Eric B. Lim, Lyndell L. Beardsley, Robert M. Giles, Tracy R. Pasadhilka, Sirichai Lee, Shelly T. Saint Sardos, Alexandre de Butler, Nicholas J. Smith, Justine R. Rosenbaum, James T. TI Rituximab Therapy for Refractory Orbital Inflammation Results of a Phase 1/2, Dose-Ranging, Randomized Clinical Trial SO JAMA OPHTHALMOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; EYE DISEASE; EFFICACY; MANAGEMENT; CYCLOPHOSPHAMIDE; VASCULITIS; RADIATION; SAFETY AB IMPORTANCE Orbital inflammation is a potentially blinding and disfiguring disease process that is often treated with systemic corticosteroids and immunosuppression; better treatments are needed. OBJECTIVE To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation. DESIGN, SETTING, AND PARTICIPANTS A dose-ranging, randomized, double-masked phase 1/2 clinical trial was conducted at a tertiary referral ophthalmology clinic. Ten individuals with orbital inflammation refractory to systemic corticosteroids and at least 1 other immunosuppressive agent were enrolled from January 2007 to March 2010. INTERVENTIONS Rituximab infusions were administered on study days 1 and 15 at doses of either 500 mg or 1000 mg. Initial responders with recurrent inflammation after week 24 were permitted reinfusion with an additional cycle of 2 open-label 1000-mg rituximab infusions. MAIN OUTCOMES AND MEASURES The primary outcomes were reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50%. The secondary outcomes were visual acuity, reduction in pain, and participantand physician-reported global health assessment. RESULTS Of 10 enrolled patients, 7 demonstrated improvement on the orbital disease grading scale at the 24-week end point with rituximab therapy. Of these 7 individuals, 4 were receiving corticosteroids at study inception and all achieved successful dose reduction. For the secondary outcome measures in the 10 participants, 7 patients and 8 patients improved in self-rated and physician global health scores, respectively, and 7 patients had reduction in pain by 25% or more at 24 weeks. Four patients who were positive responders at the week 24 end point experienced breakthrough inflammation after week 24 and received reinfusions between 24 and 48 weeks. Vision remained stable in all participants. Three of 10 patients had short-term objective or subjective worsening 2 to 8 weeks after receiving rituximab infusions, which was averted in subsequent patients with oral corticosteroids administered during the infusion and did not affect the eventual positive treatment outcome. No significant differences with regard to efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. CONCLUSIONS AND RELEVANCE Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation. C1 [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Suhler, Eric B.; Lim, Lyndell L.; Beardsley, Robert M.; Giles, Tracy R.; Pasadhilka, Sirichai; Lee, Shelly T.; Saint Sardos, Alexandre de; Butler, Nicholas J.; Smith, Justine R.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97239 USA. [Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Suhler, Eric B.; Lim, Lyndell L.] Univ Melbourne, Dept Ophthalmol, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Lim, Lyndell L.] Royal Victorian Eye & Ear Hosp, Dept Ophthalmol, Melbourne, Vic 3002, Australia. [Smith, Justine R.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Cell Biol, Portland, OR 97201 USA. [Smith, Justine R.] Flinders Univ S Australia, Adelaide, SA 5001, Australia. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Rosenbaum, James T.] Devers Eye Inst, Dept Ophthalmol, Portland, OR USA. RP Suhler, EB (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM suhlere@ohsu.edu OI Lim, Lyndell/0000-0003-2491-685X FU Genentech, San Francisco, California; Department of Veterans' Affairs; Research to Prevent Blindness (unrestricted grant to Casey Eye Institute, Senior Scholar Award to Dr Rosenbaum); Rosenfeld Family Trust; William and Mary Bauman Foundation FX Study expenses and drug were provided by Genentech, San Francisco, California. Additional research support was provided by the Department of Veterans' Affairs (Dr Suhler), Research to Prevent Blindness (unrestricted grant to Casey Eye Institute, Senior Scholar Award to Dr Rosenbaum), the Rosenfeld Family Trust (Dr Rosenbaum), and the William and Mary Bauman Foundation. NR 32 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAY PY 2014 VL 132 IS 5 BP 572 EP 578 DI 10.1001/jamaophthalmol.2013.8179 PG 7 WC Ophthalmology SC Ophthalmology GA AJ7QW UT WOS:000337892500009 PM 24652467 ER PT J AU Sanders, DS Read-Brown, S Tu, DC Lambert, WE Choi, D Almario, BM Yackel, TR Brown, AS Chiang, MF AF Sanders, David S. Read-Brown, Sarah Tu, Daniel C. Lambert, William E. Choi, Dongseok Almario, Bella M. Yackel, Thomas R. Brown, Anna S. Chiang, Michael F. TI Impact of an Electronic Health Record Operating Room Management System in Ophthalmology on Documentation Time, Surgical Volume, and Staffing SO JAMA OPHTHALMOLOGY LA English DT Article ID MEDICAL-RECORDS; INFORMATION-TECHNOLOGY; AMERICAN-ACADEMY; MEANINGFUL USE; PRIMARY-CARE; PHYSICIANS; EFFICIENCY; ADOPTION; COSTS; PAPER AB IMPORTANCE Although electronic health record (EHR) systems have potential benefits, such as improved safety and quality of care, most ophthalmology practices in the United States have not adopted these systems. Concerns persist regarding potential negative impacts on clinical workflow. In particular, the impact of EHR operating room (OR) management systems on clinical efficiency in the ophthalmic surgery setting is unknown. OBJECTIVE To determine the impact of an EHR OR management system on intraoperative nursing documentation time, surgical volume, and staffing requirements. DESIGN. SETTING, AND PARTICIPANTS For documentation time and circulating nurses per procedure, a prospective cohort design was used between January 10, 2012, and January 10, 2013. For surgical volume and overall staffing requirements, a case series design was used between January 29, 2011, and January 28, 2013. This study involved ophthalmic OR nurses (n = 13) and surgeons (n = 25) at an academic medical center. EXPOSURES Electronic health record OR management system implementation. MAIN OUTCOMES AND MEASURES (1) Documentation time (percentage of operating time documenting [POTD], absolute documentation time in minutes), (2) surgical volume (procedures/time), and (3) staffing requirements (full-time equivalents, circulating nurses/procedure). Outcomes were measured during a baseline period when paper documentation was used and during the early (first 3 months) and late (4-12 months) periods after EHR implementation. RESULTS There was a worsening in total POTD in the early EHR period (83%) vs paper baseline (41%) (P <.001). This improved to baseline levels by the late EHR period (46%, P =.28), although POTD in the cataract group remained worse than at baseline (64%, P <.001). There was a worsening in absolute mean documentation time in the early EHR period (16.7 minutes) vs paper baseline (7.5 minutes) (P <.001). This improved in the late EHR period (9.2 minutes) but remained worse than in the paper baseline (P <.001). While cataract procedures required more circulating nurses in the early EHR (mean, 1.9 nurses/procedure) and late EHR (mean, 1.5 nurses/procedure) periods than in the paper baseline (mean, 1.0 nurses/procedure) (P <.001), overall staffing requirements and surgical volume were not significantly different between the periods. CONCLUSIONS AND RELEVANCE Electronic health record OR management system implementation was associated with worsening of intraoperative nursing documentation time especially in shorter procedures. However, it is possible to implement an EHR OR management system without serious negative impacts on surgical volume and staffing requirements. C1 [Sanders, David S.; Read-Brown, Sarah; Tu, Daniel C.; Almario, Bella M.; Brown, Anna S.; Chiang, Michael F.] Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97239 USA. [Tu, Daniel C.] Portland VA Med Ctr, Operat Care Div, Portland, OR USA. [Lambert, William E.; Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Yackel, Thomas R.; Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Chiang, MF (reprint author), Oregon Hlth & Sci Univ, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM chiangm@ohsu.edu OI Read-Brown, Sarah/0000-0002-6526-2939 FU Research to Prevent Blindness (New York, New York); National Institutes of Health [EY10572] FX This work was supported by unrestricted departmental funding from Research to Prevent Blindness (New York, New York) (Mr Sanders, Mss Read-Brown and Brown, and Drs Tu and Chiang). Dr Choi is supported by National Institutes of Health grant EY10572. NR 33 TC 6 Z9 6 U1 7 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAY PY 2014 VL 132 IS 5 BP 586 EP 592 DI 10.1001/jamaophthalmol.2013.8196 PG 7 WC Ophthalmology SC Ophthalmology GA AJ7QW UT WOS:000337892500011 PM 24676217 ER PT J AU Ding, J Sullivan, DA AF Ding, Juan Sullivan, David A. TI The Effects of Insulin-like Growth Factor 1 and Growth Hormone on Human Meibomian Gland Epithelial Cells SO JAMA OPHTHALMOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY CP-751,871; DRY EYE DISEASE; INTERNATIONAL WORKSHOP; 3-KINASE/AKT PATHWAY; UTILITY-ASSESSMENT; DYSFUNCTION REPORT; SEBACEOUS GLANDS; GENE-EXPRESSION; SEBOCYTES; SUBCOMMITTEE AB IMPORTANCE A phase 1 study has reported that dry eye disease is the most common adverse effect of human exposure to the antibody figitumumab, an anticancer drug that prevents insulin-like growth factor 1 (IGF-1) from binding to its receptor. We hypothesized that the mechanism underlying this effect is the inhibition of IGF-1 action in epithelial cells of the meibomian gland. OBJECTIVES To test the hypothesis that IGF-1 stimulates meibomian gland function in vitro and to examine whether growth hormone, a closely related hormone of IGF-1, has the same effect. DESIGN, SETTING, AND MATERIAL Immortalized human meibomian gland epithelial cells were cultured in the presence or the absence of IGF-1, growth hormone, and an IGF-1 receptor-blocking antibody. Signaling pathways, cell proliferation, neutral lipid staining, and a key protein involved in lipid biogenesis were evaluated. INTERVENTION Application of IGF-1 and growth hormone to human meibomian gland epithelial cells. MAIN OUTCOMES AND MEASURES Immunoblotting, cell counting, and neutral lipid staining. RESULTS Insulin-like growth factor 1 activated the phosphoinositol 3-kinase/Akt and forkhead box 01 pathways (showing a dose-dependent effect on immunoblotting), stimulated cellular proliferation (about 1.8-fold increase in cell number), increased sterol regulatory element-binding protein 1 expression (about 3-fold increase on immunoblotting), and promoted lipid accumulation in human meibomian gland epithelial cells (about 2-fold increase in lipid staining). These IGF-1 actions, which may be blocked by cotreatment with the anti-IGF-1 antibody, were accompanied by inconsistent effects on extracellular signal-regulated kinase phosphorylation. We were not able to demonstrate activation of Akt, forkhead box 01, extracellular signal-regulated kinase, Janus kinase 2, or signal transducers and activators of transcription 5, induced cell proliferation, or lipid accumulation in these cells by growth hormone application. CONCLUSIONS AND RELEVANCE Our results support the hypothesis that IGF-1 acts on human meibomian gland epithelial cells and may explain why treatment with figitumumab, the IGF-1 inhibitor, causes dry eye disease. Ophthalmic care for dry eye disease may be needed when patients with cancer undergo treatment with drugs that inhibit IGF-1 action. C1 [Ding, Juan; Sullivan, David A.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Ding, Juan; Sullivan, David A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ding, J (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM juan_ding@meei.harvard.edu FU National Institutes of Health [RO1EYO5612]; Margaret S. Sinon Scholar in Ocular Surface Research Fund; ARVO Foundation for Eye Research/Vistakon Dry Eye Fellowship FX This study was supported by grant RO1EYO5612 from the National Institutes of Health; by the Margaret S. Sinon Scholar in Ocular Surface Research Fund; and by the ARVO Foundation for Eye Research/Vistakon Dry Eye Fellowship. NR 41 TC 6 Z9 6 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAY PY 2014 VL 132 IS 5 BP 593 EP 599 DI 10.1001/jamaophthalmol.2013.8295 PG 7 WC Ophthalmology SC Ophthalmology GA AJ7QW UT WOS:000337892500012 PM 24743973 ER PT J AU Nguyen, MT Berger, RL Hicks, SC Davila, JA Li, LT Kao, LS Liang, MK AF Nguyen, Mylan T. Berger, Rachel L. Hicks, Stephanie C. Davila, Jessica A. Li, Linda T. Kao, Lillian S. Liang, Mike K. TI Comparison of Outcomes of Synthetic Mesh vs Suture Repair of Elective Primary Ventral Herniorrhaphy A Systematic Review and Meta-analysis SO JAMA SURGERY LA English DT Review ID HEALTH-CARE INTERVENTIONS; UMBILICAL HERNIA; EPIDEMIOLOGY; EXPERIENCE; ADULTS; COST AB IMPORTANCE More than 350 000 ventral hernias are repaired in the United States annually, of which 75% are primary ventral hernias (eg, umbilical or epigastric hernias). Despite the volume, there is insufficient evidence to support the use of sutures vs mesh for primary ventral hernia repairs. OBJECTIVE To compare suture vs mesh repairs for 3 outcomes: hernia recurrence, surgical site infection (SSI), and seromas. DATA SOURCES Randomized controlled trials, case-control, and cohort studies were identified from OVID, PubMed, and reference lists from January 1, 1980, through June 1, 2012. STUDY SELECTION English-language studies with adult patients were eligible for review if there was mention of both suture and mesh techniques used during elective repair of a primary ventral hernia. Two study authors independently reviewed the 1492 articles originally identified and selected 9 for analysis. The Downs and Black 26-item checklist was used to critically assess the risk of bias. DATA EXTRACTION Year of publication, study design, inclusion and exclusion criteria, number of patients, follow-up duration, use of preoperative antibiotics, size of hernias repaired, age, body mass index (calculated as weight in kilograms divided by height in meters squared), American Society of Anesthesiologists grade, repair techniques, incidence of hernia recurrence, seroma, and SSI. DATA EXTRACTION AND SYNTHESIS Three separate univariate meta-analyses for each end point followed by a multivariate meta-analysis were performed. Across all 9 studies, there were 637 mesh repairs and 1145 suture repairs. The pooled mesh repairs demonstrated a 2.7% recurrence rate, 7.7% seroma rate, and 7.3% SSI rate The pooled suture repairs demonstrated an 8.2% recurrence rate, 3.8% seroma rate, and 6.6% SSI rate. On the basis of results from the multivariate meta-analysis, recurrences (log odds ratio, -1.04; 95% CI, -1.58 to -0.52) were more common with suture repair, whereas seromas (0.84; 0.27-1.41) and SSIs (0.65; 0.12-1.18) were more common with mesh repair. CONCLUSIONS AND RELEVANCE Mesh repair has a small reduction in recurrence rates compared with suture repairs for primary ventral hernias, but an increased risk of seroma and SSI was observed. Further high-quality studies are necessary to determine whether suture or mesh repair leads to improved outcomes for primary ventral hernias. C1 [Nguyen, Mylan T.; Kao, Lillian S.; Liang, Mike K.] Univ Texas Houston, Hlth Sci Ctr, Dept Surg, Houston, TX 77026 USA. [Berger, Rachel L.; Li, Linda T.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Hicks, Stephanie C.] Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA. [Davila, Jessica A.] Baylor Coll Med, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Houston, TX 77030 USA. RP Liang, MK (reprint author), Univ Texas Houston, Hlth Sci Ctr, Dept Surg, Lyndon B Johnson Hosp, 5656 Kelley St, Houston, TX 77026 USA. EM mkliang@yahoo.com RI Liang, Mike/L-8493-2015 OI Liang, Mike/0000-0001-7063-7291 FU Lifecell; Acell FX Dr Liang is currently receiving a grant from Lifecell and Acell. No other disclosures were reported. NR 23 TC 38 Z9 38 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAY PY 2014 VL 149 IS 5 BP 415 EP 421 DI 10.1001/jamasurg.2013.5014 PG 7 WC Surgery SC Surgery GA AJ7VR UT WOS:000337908600003 PM 24554114 ER PT J AU Hyder, O Marques, H Pulitano, C Marsh, JW Alexandrescu, S Bauer, TW Gamblin, TC Sotiropoulos, GC Paul, A Barroso, E Clary, BM Aldrighetti, L Ferrone, CR Zhu, AX Popescu, I Gigot, JF Mentha, G Feng, S Pawlik, TM AF Hyder, Omar Marques, Hugo Pulitano, Carlo Marsh, J. Wallis Alexandrescu, Sorin Bauer, Todd W. Gamblin, T. Clark Sotiropoulos, Georgios C. Paul, Andreas Barroso, Eduardo Clary, Bryan M. Aldrighetti, Luca Ferrone, Cristina R. Zhu, Andrew X. Popescu, Irinel Gigot, Jean-Francois Mentha, Gilles Feng, Shen Pawlik, Timothy M. TI A Nomogram to Predict Long-term Survival After Resection for Intrahepatic Cholangiocarcinoma An Eastern and Western Experience SO JAMA SURGERY LA English DT Article ID PROGNOSTIC NOMOGRAM; RECURRENCE; ADENOCARCINOMA; HEPATECTOMY; CANCER; SYSTEM AB IMPORTANCE Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined. OBJECTIVE To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram. DESIGN, SETTING, AND PARTICIPANTS We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots. INTERVENTIONS Surgical resection of ICC at a participating hospital. MAIN OUTCOMES AND MEASURES Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram. RESULTS Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients ( 74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (< 3 segments) (132 [25.7%]). Most patients underwent RO resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P <.001), tumor size (HR, 1.50; P <.001), multiple tumors (HR, 1.58; P <.001), cirrhosis (HR, 1.51; P =.08), lymph node metastasis (HR, 1.78; P =.01), and macrovascular invasion (HR, 2.10; P <.001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692). CONCLUSIONS AND RELEVANCE On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC. C1 [Hyder, Omar; Pawlik, Timothy M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. [Marques, Hugo; Barroso, Eduardo] Curry Cabral Hosp, Dept Surg, Lisbon, Portugal. [Pulitano, Carlo; Aldrighetti, Luca] Univ Milan, Osped San Raffaele, Dept Surg, I-20127 Milan, Italy. [Marsh, J. Wallis] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Alexandrescu, Sorin; Popescu, Irinel] Fundeni Inst, Dept Surg, Bucharest, Romania. [Bauer, Todd W.] Univ Virginia, Dept Surg, Charlottesville, VA USA. [Gamblin, T. Clark] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Sotiropoulos, Georgios C.; Paul, Andreas] Univ Hosp Essen, Dept Surg, Essen, Germany. [Clary, Bryan M.] Duke Med Ctr, Dept Surg, Durham, NC USA. [Ferrone, Cristina R.; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gigot, Jean-Francois] Clin Univ St Luc, Dept Surg, B-1200 Brussels, Belgium. [Mentha, Gilles] Hop Cantonal Univ Geneva, Dept Surg, Geneva, Switzerland. [Feng, Shen] Eastern Hepatobiliary Surg Hosp, Dept Surg, Shanghai, Peoples R China. RP Pawlik, TM (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Div Surg Oncol, 600 North Wolfe St,Blalock 688, Baltimore, MD 21287 USA. EM tpawlik1@jhmi.edu RI POPESCU, IRINEL/B-3048-2008 NR 24 TC 31 Z9 34 U1 0 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAY PY 2014 VL 149 IS 5 BP 432 EP 438 DI 10.1001/jamasurg.2013.5168 PG 7 WC Surgery SC Surgery GA AJ7VR UT WOS:000337908600007 PM 24599477 ER PT J AU Li, YH Saxena, D Chen, Z Liu, G Abrams, WR Phelan, JA Norman, RG Fisch, GS Corby, PM Dewhirst, F Paster, BJ Kokaras, AS Malamud, D AF Li, Yihong Saxena, Deepak Chen, Zhou Liu, Gaoxia Abrams, Willam R. Phelan, Joan A. Norman, Robert G. Fisch, Gene S. Corby, Patricia M. Dewhirst, Floyd Paster, Bruce J. Kokaras, Alexis S. Malamud, Daniel TI HIV Infection and Microbial Diversity in Saliva SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC PERIODONTITIS; STREPTOCOCCUS-MUTANS; POSITIVE INDIVIDUALS; INVERSE CORRELATION; SUBGINGIVAL PLAQUE; CHROMAGAR CANDIDA; ORAL MICROBIOTA AB Limited information is available about the effects of HIV and subsequent antiretroviral treatment on host-microbe interactions. This study aimed to determine the salivary microbial composition for 10 HIV-seropositive subjects, before and 6 months after highly active antiretroviral therapy (HAART), compared with that for 10 HIV-seronegative subjects. A conventional culture and two culture-independent analyses were used and consistently demonstrated differences in microbial composition among the three sets of samples. HIV-positive subjects had higher levels of total cultivable microbes, including oral streptococci, lactobacilli, Streptococcus mutans, and Candida, in saliva than did HIV-negative subjects. The total cultivable microbial levels were significantly correlated with CD4(+) T cell counts. Denaturing gradient gel electrophoresis (DGGE), which compared the overall microbial profiles, showed distinct fingerprinting profiles for each group. The human oral microbe identification microarray (HOMIM) assay, which compared the 16S rRNA genes, showed clear separation among the three sample groups. Veillonella, Synergistetes, and Streptococcus were present in all 30 saliva samples. Only minor changes or no changes in the prevalence of Neisseria, Haemophilus, Gemella, Leptotrichia, Solobacterium, Parvimonas, and Rothia were observed. Seven genera, Capnocytophaga, Slackia, Porphyromonas, Kingella, Peptostreptococcaceae, Lactobacillus, and Atopobium, were detected only in HIVnegative samples. The prevalences of Fusobacterium, Campylobacter, Prevotella, Capnocytophaga, Selenomonas, Actinomyces, Granulicatella, and Atopobium were increased after HAART. In contrast, the prevalence of Aggregatibacter was significantly decreased after HAART. The findings of this study suggest that HIV infection and HAART can have significant effects on salivary microbial colonization and composition. C1 [Li, Yihong; Saxena, Deepak; Chen, Zhou; Liu, Gaoxia; Abrams, Willam R.; Malamud, Daniel] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10012 USA. [Phelan, Joan A.] NYU, Coll Dent, Dept Oral & Maxillofacial Pathol, New York, NY USA. [Norman, Robert G.; Fisch, Gene S.] NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY USA. [Corby, Patricia M.] NYU, Coll Dent, Bluestone Ctr Clin Res, New York, NY USA. [Corby, Patricia M.] NYU, Coll Dent, Dept Periodontol & Implant Dent, New York, NY USA. [Dewhirst, Floyd; Paster, Bruce J.; Kokaras, Alexis S.] Forsyth Inst, Cambridge, MA USA. [Dewhirst, Floyd; Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Li, YH (reprint author), NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10012 USA. EM yihong.li@nyu.edu OI Malamud, Daniel/0000-0002-9094-4122 FU National Institute of Dental and Craniofacial Research [U19 DE018385] FX This study was supported by the National Institute of Dental and Craniofacial Research (grant U19 DE018385). NR 78 TC 9 Z9 9 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2014 VL 52 IS 5 BP 1400 EP 1411 DI 10.1128/JCM.02954-13 PG 12 WC Microbiology SC Microbiology GA AJ7XV UT WOS:000337915700014 PM 24523469 ER PT J AU Dingle, TC Clarridge, JE AF Dingle, Tanis C. Clarridge, Jill E., III TI Clinical Significance and Characterization of Haemophilus influenzae Type b Genogroup Isolates from Urine Samples in an Adult Male Population SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEMOPHILUS-INFLUENZAE; TRACT INFECTIONS; PARAINFLUENZAE; CHILDREN; MEN AB The occurrence and significance of Haemophilus spp. isolated from the genitourinary tract are not well known. Herein, we describe the clinical significance and characteristics of Haemophilus influenzae type b genogroup strains isolated from genitourinary tract specimens from an adult male veteran patient population and, in particular, their associations with prostatitis and epididymitis. C1 [Dingle, Tanis C.; Clarridge, Jill E., III] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Clarridge, Jill E., III] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Clarridge, JE (reprint author), Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. EM jill.clarridge@va.gov NR 19 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2014 VL 52 IS 5 BP 1745 EP 1748 DI 10.1128/JCM.00506-14 PG 4 WC Microbiology SC Microbiology GA AJ7XV UT WOS:000337915700069 PM 24599984 ER PT J AU Alzhanova, D Hammarlund, E Reed, J Meermeier, E Rawlings, S Ray, CA Edwards, DM Bimber, B Legasse, A Planer, S Sprague, J Axthelm, MK Pickup, DJ Lewinsohn, DM Gold, MC Wong, SW Sacha, JB Slifka, MK Fruh, K AF Alzhanova, Dina Hammarlund, Erika Reed, Jason Meermeier, Erin Rawlings, Stephanie Ray, Caroline A. Edwards, David M. Bimber, Ben Legasse, Alfred Planer, Shannon Sprague, Jerald Axthelm, Michael K. Pickup, David J. Lewinsohn, David M. Gold, Marielle C. Wong, Scott W. Sacha, Jonah B. Slifka, Mark K. Frueh, Klaus TI T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence SO PLOS PATHOGENS LA English DT Article ID MONKEYPOX VIRUS; COWPOX VIRUS; CONGO BASIN; CLASS-I; IMMUNODEFICIENCY VIRUS; PROTECTIVE IMMUNITY; NONHUMAN PRIMATE; AFRICAN STRAINS; DOWN-REGULATION; WEST-AFRICAN AB Infections with monkeypox, cowpox and weaponized variola virus remain a threat to the increasingly unvaccinated human population, but little is known about their mechanisms of virulence and immune evasion. We now demonstrate that B22 proteins, encoded by the largest genes of these viruses, render human T cells unresponsive to stimulation of the T cell receptor by MHC-dependent antigen presentation or by MHC-independent stimulation. In contrast, stimuli that bypass TCR-signaling are not inhibited. In a non-human primate model of monkeypox, virus lacking the B22R homologue (MPXV Delta 197) caused only mild disease with lower viremia and cutaneous pox lesions compared to wild type MPXV which caused high viremia, morbidity and mortality. Since MPXV Delta 197-infected animals displayed accelerated T cell responses and less T cell dysregulation than MPXV US2003, we conclude that B22 family proteins cause viral virulence by suppressing T cell control of viral dissemination. C1 [Alzhanova, Dina; Reed, Jason; Rawlings, Stephanie; Edwards, David M.; Sprague, Jerald; Axthelm, Michael K.; Wong, Scott W.; Sacha, Jonah B.; Frueh, Klaus] Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. [Hammarlund, Erika; Slifka, Mark K.] Oregon Natl Primate Res Ctr, Div Neurosci, Portland, OR USA. [Meermeier, Erin; Lewinsohn, David M.; Gold, Marielle C.] Oregon Hlth & Sci Univ, Dept Pulm & Crit Care Med, Portland, OR 97201 USA. [Meermeier, Erin; Lewinsohn, David M.; Gold, Marielle C.] Portland VA Med Ctr, Portland, OR USA. [Ray, Caroline A.; Pickup, David J.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. [Bimber, Ben; Legasse, Alfred; Planer, Shannon; Axthelm, Michael K.; Wong, Scott W.; Sacha, Jonah B.; Frueh, Klaus] Oregon Natl Primate Res Ctr, Div Pathobiol & Immunol, Portland, OR USA. RP Alzhanova, D (reprint author), Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. EM fruehk@ohsu.edu RI Lewinsohn, David/I-4936-2013; OI Lewinsohn, David/0000-0001-9906-9494; Gold, Marielle/0000-0003-2505-3291; Meermeier, Erin/0000-0002-9709-7624 FU National Institute of Health [U19AI109948]; National Center for Research Resources [P51OD011092]; Office of Research Infrastructure Programs of the National Institutes of Health FX This work was funded by grants U19AI109948 from the National Institute of Health and P51OD011092 from the National Center for Research Resources and the Office of Research Infrastructure Programs of the National Institutes of Health to KF and MKS and supported with resources and the use of facilities at the Portland VA Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 6 Z9 6 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004123 DI 10.1371/journal.ppat.1004123 PG 19 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300034 PM 24832205 ER PT J AU Avnir, Y Tallarico, AS Zhu, Q Bennett, AS Connelly, G Sheehan, J Sui, JH Fahmy, A Huang, CY Cadwell, G Bankston, LA McGuire, AT Stamatatos, L Wagner, G Liddington, RC Marasco, WA AF Avnir, Yuval Tallarico, Aimee S. Zhu, Quan Bennett, Andrew S. Connelly, Gene Sheehan, Jared Sui, Jianhua Fahmy, Amr Huang, Chiung-yu Cadwell, Greg Bankston, Laurie A. McGuire, Andrew T. Stamatatos, Leonidas Wagner, Gerhard Liddington, Robert C. Marasco, Wayne A. TI Molecular Signatures of Hemagglutinin Stem-Directed Heterosubtypic Human Neutralizing Antibodies against Influenza A Viruses SO PLOS PATHOGENS LA English DT Article ID MEMORY B-CELLS; SOMATIC HYPERMUTATION; STALK ANTIBODIES; GERMINAL CENTER; MARGINAL ZONE; COPY-NUMBER; IMMUNOGLOBULIN; REPERTOIRE; DESIGN; DOMAIN AB Recent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs). Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met) and Phe54), and CDR-H3-Tyr at positions 98 +/- 1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-eta recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/pol eta restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a) facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination. C1 [Avnir, Yuval; Tallarico, Aimee S.; Zhu, Quan; Bennett, Andrew S.; Connelly, Gene; Sheehan, Jared; Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Med, Boston, MA 02115 USA. [Fahmy, Amr; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Huang, Chiung-yu] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Cadwell, Greg; Bankston, Laurie A.; Liddington, Robert C.] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA USA. [McGuire, Andrew T.; Stamatatos, Leonidas] Seattle Biomed Res Inst, Seattle, WA 98109 USA. RP Avnir, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Med, 44 Binney St, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU National Institutes of Health [NIAID U01-AI074518, NIAID P01 AI094419-01]; Defense Advanced Research Projects Agency [W911NF-10-1-0266] FX This work was supported by the following grants from the National Institutes of Health: NIAID U01-AI074518 to WAM and RCL and NIAID P01 AI094419-01 to LS. This work was also funded by the Defense Advanced Research Projects Agency's "7-Day Biodefense" program under contract # W911NF-10-1-0266 to WAM. The views expressed are those of the author and do not reflect the official policy or position of the Department of Defense or the U.S. Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 29 Z9 29 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004103 DI 10.1371/journal.ppat.1004103 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300021 PM 24788925 ER PT J AU Park, YD Shin, S Panepinto, J Ramos, J Qiu, J Frases, S Albuquerque, P Cordero, RJB Zhang, NN Himmelreich, U Beenhouwer, D Bennett, JE Casadevall, A Williamson, PR AF Park, Yoon-Dong Shin, Soowan Panepinto, John Ramos, Jeanie Qiu, Jin Frases, Susana Albuquerque, Patricia Cordero, Radames J. B. Zhang, Nannan Himmelreich, Uwe Beenhouwer, David Bennett, John E. Casadevall, Arturo Williamson, Peter R. TI A Role for LHC1 in Higher Order Structure and Complement Binding of the Cryptococcus neoformans Capsule SO PLOS PATHOGENS LA English DT Article ID POLYSACCHARIDE CAPSULE; MONOCLONAL-ANTIBODIES; FUSARIUM-OXYSPORUM; VIRULENCE FACTOR; LACCASE; CELL; ACTIVATION; COMPONENTS; INFECTION; STRAINS AB Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1 (Delta) over bar strains by dynamic and static light scattering suggested a role for the LHC1 locus in altering the capsular polysaccharide, both reducing dimensions and altering its branching, density and solvation. These changes in the capsular structure resulted in LHC1-dependent alterations of antibody binding patterns, reductions in human and mouse complement binding and phagocytosis by the macrophage-like cell line J774, as well as increased virulence in mice. These findings identify a unique molecular mechanism for tertiary structural changes in a microbial capsule, facilitating immune evasion and virulence of a fungal pathogen. C1 [Park, Yoon-Dong; Qiu, Jin; Zhang, Nannan; Bennett, John E.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Shin, Soowan; Ramos, Jeanie; Williamson, Peter R.] Univ Illinois, Dept Med, Coll Med, Infect Dis Sect, Chicago, IL USA. [Panepinto, John] SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14260 USA. [Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Casadevall, Arturo] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Casadevall, Arturo] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10467 USA. [Frases, Susana] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Cellular Hertha Meyer, BR-21941 Rio De Janeiro, Brazil. [Himmelreich, Uwe] Katholieke Univ Leuven, Div Radiol, Dept Med Diagnost Sci, Biomed NMR Unit, Leuven, Belgium. [Beenhouwer, David] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Beenhouwer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Park, YD (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM williamsonpr@mail.nih.gov RI Albuquerque, Patricia/H-1403-2011; OI Cordero, Radames JB/0000-0002-3026-7094 FU United States Public Health Service [NIH-AI45995, AI49371, AI007506, AI033142, AI47087, HL059842-3, A1033774, A1052733, AI033142.]; Flemish government [FWO G.0804.11]; KUL [PF10/017]; CAPES-Brazil; NIH, NIAID FX This work was supported, in part, by United States Public Health Service Grants NIH-AI45995, AI49371, AI007506, AI033142, AI47087, HL059842-3, A1033774, A1052733, and AI033142. Flemish governmental funding FWO G.0804.11 and KUL funding PF10/017 and a CAPES-Brazil/Fulbright scholarship (PA). This research was also supported, in part, by the Intramural Research Program of the NIH, NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 5 Z9 5 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004037 DI 10.1371/journal.ppat.1004037 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300003 PM 24789368 ER PT J AU Pukkila-Worley, R Feinbaum, RL McEwan, DL Conery, AL Ausubel, FM AF Pukkila-Worley, Read Feinbaum, Rhonda L. McEwan, Deborah L. Conery, Annie L. Ausubel, Frederick M. TI The Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxification SO PLOS PATHOGENS LA English DT Article ID CAENORHABDITIS-ELEGANS; PSEUDOMONAS-AERUGINOSA; C. ELEGANS; TRANSLATIONAL INHIBITION; INFECTION; PATHOGEN; MODEL; RESISTANCE; INTEGRATION; MECHANISMS AB Metazoans protect themselves from environmental toxins and virulent pathogens through detoxification and immune responses. We previously identified a small molecule xenobiotic toxin that extends survival of Caenorhabditis elegans infected with human bacterial pathogens by activating the conserved p38 MAP kinase PMK-1 host defense pathway. Here we investigate the cellular mechanisms that couple activation of a detoxification response to innate immunity. From an RNAi screen of 1,420 genes expressed in the C. elegans intestine, we identified the conserved Mediator subunit MDT-15/MED15 and 28 other gene inactivations that abrogate the induction of PMK-1-dependent immune effectors by this small molecule. We demonstrate that MDT-15/MED15 is required for the xenobiotic-induced expression of p38 MAP kinase PMK1-dependent immune genes and protection from Pseudomonas aeruginosa infection. We also show that MDT-15 controls the induction of detoxification genes and functions to protect the host from bacteria-derived phenazine toxins. These data define a central role for MDT-15/MED15 in the coordination of xenobiotic detoxification and innate immune responses. C1 [Pukkila-Worley, Read] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02163 USA. [Pukkila-Worley, Read; Feinbaum, Rhonda L.; McEwan, Deborah L.; Conery, Annie L.; Ausubel, Frederick M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. [Pukkila-Worley, Read; Feinbaum, Rhonda L.; McEwan, Deborah L.; Conery, Annie L.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Pukkila-Worley, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02163 USA. EM rpukkilaworley@partners.org FU Cancer Research Institute-Irvington Institute Fellowship Program; National Institutes of Health [K08 AI081747, F32 AI098307, R01 AI085581, P01 AI083214] FX This study was supported by the Cancer Research Institute-Irvington Institute Fellowship Program (to RPW) and by National Institutes of Health awards K08 AI081747 (to RPW), F32 AI098307 (to DLM), R01 AI085581 (to FMA), and P01 AI083214 (to FMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 11 Z9 11 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004143 DI 10.1371/journal.ppat.1004143 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300047 PM 24875643 ER PT J AU Xiao, F Fofana, I Heydmann, L Barth, H Soulier, E Habersetzer, F Doffoel, M Bukh, J Patel, AH Zeisel, MB Baumert, TF AF Xiao, Fei Fofana, Isabel Heydmann, Laura Barth, Heidi Soulier, Eric Habersetzer, Francois Doffoel, Michel Bukh, Jens Patel, Arvind H. Zeisel, Mirjam B. Baumert, Thomas F. TI Hepatitis C Virus Cell-Cell Transmission and Resistance to Direct-Acting Antiviral Agents SO PLOS PATHOGENS LA English DT Article ID B TYPE-I; NEUTRALIZING ANTIBODIES; HUMAN HEPATOCYTES; NS5A INHIBITORS; HEPATOMA-CELLS; ENTRY FACTORS; GENOTYPE 1; INFECTION; THERAPY; HCV AB Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to directacting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs. C1 [Xiao, Fei; Fofana, Isabel; Heydmann, Laura; Barth, Heidi; Soulier, Eric; Habersetzer, Francois; Doffoel, Michel; Zeisel, Mirjam B.; Baumert, Thomas F.] INSERM, U1110, Strasbourg, France. [Xiao, Fei; Fofana, Isabel; Heydmann, Laura; Barth, Heidi; Soulier, Eric; Habersetzer, Francois; Doffoel, Michel; Zeisel, Mirjam B.; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Barth, Heidi] Hop Univ Strasbourg, Lab Virol, Strasbourg, France. [Habersetzer, Francois; Doffoel, Michel; Baumert, Thomas F.] Hop Univ Strasbourg, Strasbourg, France. [Bukh, Jens] Univ Copenhagen, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, Copenhagen, Denmark. [Bukh, Jens] Univ Copenhagen, Hvidovre Hosp, Clin Res Ctr, Copenhagen, Denmark. [Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth & Med Sci, Copenhagen, Denmark. [Patel, Arvind H.] Univ Glasgow, Ctr Virus Res, MRC, Glasgow, Lanark, Scotland. [Baumert, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Xiao, F (reprint author), INSERM, U1110, Strasbourg, France. EM Thomas.Baumert@unistra.fr RI Zeisel, Mirjam/E-9205-2016 OI Zeisel, Mirjam/0000-0003-1606-0131 FU Inserm; University of Strasbourg; European Union [ERC-2008-AdG-233130-HEPCENT]; ANRS [2011/132, 2012/239, 2012/318, 2013/108]; Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir) [ANR-10-LAB-28]; Direction Generale de l'Offre de Soins [A12027MS] FX This work was supported by Inserm, University of Strasbourg, the European Union (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net 2009 and 2012), ANRS (2011/132, 2012/239, 2012/318, 2013/108), Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir; ANR-10-LAB-28), the Direction Generale de l'Offre de Soins (A12027MS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 29 Z9 30 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004128 DI 10.1371/journal.ppat.1004128 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300037 PM 24830295 ER PT J AU Turner, AP Sloan, AP Kivlahan, DR Haselkorn, JK AF Turner, Aaron P. Sloan, Alicia P. Kivlahan, Daniel R. Haselkorn, Jodie K. TI Telephone Counseling and Home Telehealth Monitoring to Improve Medication Adherence: Results of a Pilot Trial Among Individuals With Multiple Sclerosis SO REHABILITATION PSYCHOLOGY LA English DT Article DE multiple sclerosis; medication adherence; motivational interviewing; self-management; telehealth ID DISEASE-MODIFYING THERAPIES; RANDOMIZED CONTROLLED-TRIAL; TRAUMATIC BRAIN-INJURY; QUALITY-OF-LIFE; INJECTION ANXIETY; CHRONIC ILLNESS; PRIMARY-CARE; SELF-INJECT; ALCOHOL-DEPENDENCE; DEPRESSION AB Objective: To evaluate the impact upon medication adherence of brief telephone-based counseling using principles of motivational interviewing and telehealth home monitoring. Design: Randomized controlled pilot trial of 19 veterans with multiple sclerosis (MS) currently prescribed disease modifying therapy (DMT) who endorsed missing doses. Follow-up was conducted at 1, 3, and 6 months. Results: Participants in the intervention condition reported better adherence relative to controls at 6-month follow-up [M (SD) = 1.3 (2.1) vs. 8.2 (12.3) past month missed doses]. All participants in the intervention condition completed all 3 telephone counseling sessions and 90% or greater rated the program as highly successful. Conclusion: Brief telephone counseling represents a promising mechanism for improving medication adherence. The primary components, motivational interviewing and home telehealth monitoring, provided complementary mechanisms for initiating and sustaining behavior change over time. The intervention was well tolerated and provided an opportunity to extend access and reduce barriers to care by bringing it into the homes of participants. C1 [Turner, Aaron P.; Sloan, Alicia P.; Kivlahan, Daniel R.; Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Turner, Aaron P.; Sloan, Alicia P.; Haselkorn, Jodie K.] VA MS Ctr Excellence West, Seattle, WA USA. [Turner, Aaron P.; Kivlahan, Daniel R.] VA Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Turner, Aaron P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, VA Puget Sound Hlth Care Syst, VA MS Ctr Excellence West, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@med.va.gov OI sloan, alicia/0000-0003-4891-3266; Turner, Aaron/0000-0001-6897-8003 NR 75 TC 4 Z9 4 U1 4 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD MAY PY 2014 VL 59 IS 2 BP 136 EP 146 DI 10.1037/a0036322 PG 11 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA AJ7SQ UT WOS:000337897800003 PM 24708232 ER PT J AU Bambara, JK Turner, AP Williams, RM Haselkorn, JK AF Bambara, Jennifer K. Turner, Aaron P. Williams, Rhonda M. Haselkorn, Jodie K. TI Social Support and Depressive Symptoms Among Caregivers of Veterans With Multiple Sclerosis SO REHABILITATION PSYCHOLOGY LA English DT Article DE multiple sclerosis; caregiver; social support; depression; veterans ID DISEASE-MODIFYING THERAPIES; QUALITY-OF-LIFE; FAMILY CAREGIVERS; HEALTH; IMPAIRMENT; ADHERENCE; VALIDATION; DISABILITY; ADJUSTMENT; VALIDITY AB Purpose/Objective: The primary aim of this study was to examine the relationship between perceived social support and depressive symptoms among family caregivers of veterans with multiple sclerosis (MS). A secondary aim of this study was to examine the relationship between caregiver perceived social support and caregiver demographic variables, veteran health-related variables, and caregiver depressive symptoms. Research Method/Design: As part of a larger study, 42 family caregivers of veterans with MS completed questionnaires by telephone. Hierarchical regression was used to examine the relationship between caregiver depressive symptoms and perceived social support. Results: Greater MS disease severity and poorer overall veteran health were associated with higher levels of depressive symptoms among caregivers. Caregiver perceived social support was associated with depressive symptoms after controlling for veterans' MS disease severity and overall physical health. Conclusions/Implications: Psychosocial interventions aimed at enhancing social support among caregivers of veterans with MS in multiple life domains, such as work, finances, housing, social life, marriage, and family, may be important for family caregiver mood management, particularly as MS disease severity increases. C1 [Bambara, Jennifer K.; Turner, Aaron P.; Williams, Rhonda M.; Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Turner, Aaron P.; Haselkorn, Jodie K.] VA MS Ctr Excellence West, Seattle, WA USA. [Turner, Aaron P.; Williams, Rhonda M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med & Epidemiol, Seattle, WA 98195 USA. RP Bambara, JK (reprint author), Vet Adm Puget Sound Hlth Care Syst, Seattle Div, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM jennifer.bambara@va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 29 TC 1 Z9 1 U1 2 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD MAY PY 2014 VL 59 IS 2 BP 230 EP 235 DI 10.1037/a0036312 PG 6 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA AJ7SQ UT WOS:000337897800014 PM 24730574 ER PT J AU Lakshmanan, S Gupta, GK Avci, P Chandran, R Sadasivam, M Jorge, AES Hamblin, MR AF Lakshmanan, Shanmugamurthy Gupta, Gaurav K. Avci, Pinar Chandran, Rakkiyappan Sadasivam, Magesh Serafim Jorge, Ana Elisa Hamblin, Michael R. TI Physical energy for drug delivery; poration, concentration and activation SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Electroporation; Gene transfection; Magnetoporation; Nanoparticles; Optoporation; Photothermal therapy; Smart drug carriers; Sonoporation; Thermoporation ID NORMAL RAT-BRAIN; LOW-FREQUENCY SONOPHORESIS; IRON-OXIDE NANOPARTICLES; CELL-MEMBRANE POROSITY; MEDIATED GENE-TRANSFER; NAKED PLASMID DNA; IN-VIVO; PHOTODYNAMIC THERAPY; CARBON NANOTUBES; TRANSDERMAL DELIVERY AB Techniques for controlling the rate and duration of drug delivery, while targeting specific locations of the body for treatment, to deliver the cargo (drugs or DNA) to particular parts of the body by what are becoming called "smart drug carriers" have gained increased attention during recent years. Using such smart carriers, researchers have also been investigating a number of physical energy forces including: magnetic fields, ultrasound, electric fields, temperature gradients, photoactivation or photorelease mechanisms, and mechanical forces to enhance drug delivery within the targeted cells or tissues and also to activate the drugs using a similar or a different type of external trigger. This review aims to cover a number of such physical energy modalities. Various advanced techniques such as magnetoporation, electroporation, iontophoresis, sonoporation/mechnoporation, phonophoresis, optoporation and thermoporation will be covered in the review. Special emphasis will be placed on photodynamic therapy owing to the experience of the authors' laboratory in this area, but other types of drug cargo and DNA vectors will also be covered. Photothermal therapy and theranostics will also be discussed. (C) 2013 Elsevier B.V. All rights reserved. C1 [Lakshmanan, Shanmugamurthy; Gupta, Gaurav K.; Avci, Pinar; Chandran, Rakkiyappan; Sadasivam, Magesh; Serafim Jorge, Ana Elisa; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lakshmanan, Shanmugamurthy; Gupta, Gaurav K.; Avci, Pinar; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02119 USA. [Serafim Jorge, Ana Elisa] Univ Sao Paulo, Inst Fis Sao Carlos, Programa Posgrad Interunidades Bioengn EESC FMRP, Sao Carlos, SP, Brazil. [Serafim Jorge, Ana Elisa] Univ Sao Paulo, Inst Fis Sao Carlos, Lab Biofoton, Sao Carlos, SP, Brazil. RP Hamblin, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,BAR Wellman Ctr Photomed 414, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875] FX This work was supported by the US NIH (R01AI050875 to MRH). NR 236 TC 25 Z9 27 U1 10 U2 93 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY PY 2014 VL 71 BP 98 EP 114 DI 10.1016/j.addr.2013.05.010 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ4MD UT WOS:000337649600008 PM 23751778 ER PT J AU Michaud, DS Izard, J AF Michaud, Dominique S. Izard, Jacques TI Microbiota, Oral Microbiome, and Pancreatic Cancer SO CANCER JOURNAL LA English DT Review DE Periodontitis; inflammation; digestive tract; pancreas ID HELICOBACTER-PYLORI SEROPOSITIVITY; ABO BLOOD-GROUP; PERIODONTAL-DISEASE; GASTRIC-CANCER; ENDOGENOUS FORMATION; TOOTH LOSS; INFECTION; RISK; ASSOCIATION; PATHOGEN AB Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after the diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest that the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease susceptibility, should shed light on how to better tackle prevention, early detection, and treatment of this highly fatal disease. C1 [Michaud, Dominique S.] Brown Univ, Dept Epidemiol, Sch Publ Hlth, Providence, RI 02912 USA. [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Izard, Jacques] Forsyth Inst, Cambridge, MA USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Michaud, DS (reprint author), Brown Univ, Dept Epidemiol, Box G-S121-2, Providence, RI 02912 USA. EM Dominique_Michaud@brown.edu RI Michaud, Dominique/I-5231-2014; OI Izard, Jacques/0000-0002-5904-5436 FU National Institutes of Health [CA166150, DK097153] FX Our team is supported by grants from the National Institutes of Health CA166150 (DSM and JI) and DK097153 (JI). NR 59 TC 12 Z9 13 U1 0 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD MAY-JUN PY 2014 VL 20 IS 3 BP 203 EP 206 PG 4 WC Oncology SC Oncology GA AJ5FL UT WOS:000337708000007 PM 24855008 ER PT J AU Faez, S Lobo, AM Sobrin, L Papaliodis, GN AF Faez, Sepideh Lobo, Ann-Marie Sobrin, Lucia Papaliodis, George N. TI Treatment of seronegative spondyloarthropathy-associated uveitis with golimumab: retrospective case series SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter C1 [Faez, Sepideh; Lobo, Ann-Marie; Sobrin, Lucia; Papaliodis, George N.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Uveitis Serv, Boston, MA 02163 USA. [Sobrin, Lucia] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Retina Serv, Boston, MA USA. RP Faez, S (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Uveitis Serv, Boston, MA 02163 USA. NR 6 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 EI 1442-9071 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD MAY-JUN PY 2014 VL 42 IS 4 BP 392 EP 395 DI 10.1111/ceo.12207 PG 4 WC Ophthalmology SC Ophthalmology GA AJ3BJ UT WOS:000337539800017 PM 24024585 ER PT J AU Slow, S Priest, PC Chambers, ST Stewart, AW Jennings, LC Florkowski, CM Livesey, JH Camargo, CA Scragg, R Murdoch, DR AF Slow, S. Priest, P. C. Chambers, S. T. Stewart, A. W. Jennings, L. C. Florkowski, C. M. Livesey, J. H. Camargo, C. A., Jr. Scragg, R. Murdoch, D. R. TI Effect of vitamin D3 supplementation on Staphylococcus aureus nasal carriage: a randomized, double-blind, placebo-controlled trial in healthy adults SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Randomized controlled trial; risk factors of nasal carriage; serum 25-hydroxy vitamin D; Staphylococcus aureus nasal carriage; vitamin D3 supplementation ID METHICILLIN-RESISTANT; RISK-FACTORS; UNITED-STATES; PREVALENCE; COLONIZATION; POPULATION; INFECTIONS; COMMUNITY; DETERMINANTS AB Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and Staphylococcus aureus nasal carriage; however, clinical trials of vitamin D supplementation are lacking. To assess the effect of vitamin D3 supplementation on persistent S. aureus nasal carriage we conducted a randomized, double-blind, placebo-controlled trial among 322 healthy adults. Participants were given an oral dose of either 200 000 IU vitamin D3 for each of 2 months, followed by 100 000 IU monthly or placebo in an identical dosing regimen, for a total of 18 months. Nasal swabs for S. aureus culture and serum for 25OHD measurement were obtained at baseline, 6, 12 and 18 months of study. The mean baseline concentration of 25OHD was 72 nM (SD 22 nM). Vitamin D3 supplementation increased 25OHD levels which were maintained at >120 nM throughout the study. Nasal colonization by S. aureus was found in 31% of participants at baseline. Persistent carriage, defined as those that had positive S. aureus nasal cultures for all post-baseline swabs, occurred in 20% of the participants but vitamin D3 supplementation was not associated with a reduction in persistent carriage (OR = 1.39, 95% CI 0.63-3.06). Risk factor analysis showed that only gender was significantly associated with carriage, where women were less likely to be carriers than men (relative risk 0.83, 95% CI 0.54-0.99). Serum 25OHD concentrations were not associated with the risk of carriage. In conclusion, monthly administration of 100 000 IU of vitamin D3 did not reduce persistent S. aureus nasal carriage. C1 [Slow, S.; Chambers, S. T.; Jennings, L. C.; Florkowski, C. M.; Murdoch, D. R.] Univ Otago, Dept Pathol, Christchurch, New Zealand. [Priest, P. C.] Univ Otago, Dept Prevent & Social Med, Dunedin, New Zealand. [Chambers, S. T.] Christchurch Hosp, Dept Infect Dis, Christchurch, New Zealand. [Stewart, A. W.; Scragg, R.] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. [Jennings, L. C.; Florkowski, C. M.; Livesey, J. H.; Murdoch, D. R.] Canterbury Hlth Labs, Christchurch, New Zealand. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Slow, S (reprint author), Univ Otago, Dept Pathol, POB 4345, Christchurch, New Zealand. EM sandy.slow@otago.ac.nz OI Scragg, Robert/0000-0003-0013-2620 FU Health Research Council of New Zealand [HRC 09/302] FX This work was supported by the Health Research Council of New Zealand (HRC 09/302 to DRM). The Health Research Council was not involved in the design or conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. NR 28 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1198-743X EI 1469-0691 J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD MAY PY 2014 VL 20 IS 5 BP 453 EP 458 DI 10.1111/1469-0691.12350 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA AJ4UW UT WOS:000337674400025 PM 24004292 ER PT J AU Arsava, EM Mawet, J Eikermann-Haerter, K Park, KY Helenius, J Pearlman, L Ross, A Negro, A Daneshmand, A Ay, H Ayata, C AF Arsava, E. M. Mawet, J. Eikermann-Haerter, K. Park, K. Y. Helenius, J. Pearlman, L. Ross, A. Negro, A. Daneshmand, A. Ay, H. Ayata, C. TI Migraineurs are more susceptible to infarct growth in acute stroke SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Arsava, E. M.; Mawet, J.; Park, K. Y.; Helenius, J.; Pearlman, L.; Ross, A.; Negro, A.; Ay, H.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Arsava, E. M.] Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey. [Eikermann-Haerter, K.; Daneshmand, A.; Ayata, C.] Massachusetts Gen Hosp, Neurovasc Res Lab, Boston, MA 02114 USA. [Ay, H.; Ayata, C.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2014 VL 21 SU 1 SI SI MA EP1116 BP 112 EP 112 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ3JX UT WOS:000337563600215 ER PT J AU Gaertner, J Banwell, B Ghezzi, A Karlsson, G Li, B Merschhemke, M Putzki, N Chitnis, T AF Gaertner, J. Banwell, B. Ghezzi, A. Karlsson, G. Li, B. Merschhemke, M. Putzki, N. Chitnis, T. TI Fingolimod in paediatric multiple sclerosis: design of a double-blind study versus interferon beta-1a IM SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Gaertner, J.] Univ Gottingen, D-37073 Gottingen, Germany. [Banwell, B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Ghezzi, A.] Osped Gallarate, Gallarate, Italy. [Karlsson, G.; Merschhemke, M.; Putzki, N.] Novartis Pharma AG, Basel, Switzerland. [Li, B.] Novartis Pharmaceut, E Hanover, NJ USA. [Chitnis, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2014 VL 21 SU 1 SI SI MA EP1149 BP 130 EP 130 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ3JX UT WOS:000337563600248 ER PT J AU Fonda, JR McGlinchey, RE Rudolph, JL Milberg, WP Hunt, PR Reynolds, MW Yonan, C AF Fonda, J. R. McGlinchey, R. E. Rudolph, J. L. Milberg, W. P. Hunt, P. R. Reynolds, M. W. Yonan, C. TI Burden of pseudobulbar affect (PBA) symptoms in veterans with traumatic brain injury (TBI) SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Fonda, J. R.; McGlinchey, R. E.; Rudolph, J. L.] VA Boston Healthcare Syst, TRACTS Ctr Excellence, Boston, MA USA. [McGlinchey, R. E.; Milberg, W. P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Milberg, W. P.] VA Boston Healthcare Syst, New England GRECC Boston Div, Boston, MA USA. [Hunt, P. R.; Reynolds, M. W.] Evidera, Hlth Econ & Epidemiol, Lexington, MA USA. [Yonan, C.] Avanir Pharmaceut Inc, Hlth Econ & Outcomes Res, Aliso Viejo, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2014 VL 21 SU 1 SI SI MA PP2216 BP 537 EP 537 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ3JX UT WOS:000337563601237 ER PT J AU Plank, RM Wirth, KE Ndubuka, NO Abdullahi, R Nkgau, M Lesetedi, C Powis, KM Mmalane, M Makhema, J Shapiro, R Lockman, S AF Plank, Rebeca M. Wirth, Kathleen E. Ndubuka, Nnamdi O. Abdullahi, Rasak Nkgau, Maggie Lesetedi, Chiapo Powis, Kathleen M. Mmalane, Mompati Makhema, Joseph Shapiro, Roger Lockman, Shahin TI Single-Arm Evaluation of the AccuCirc Device for Early Infant Male Circumcision in Botswana SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AccuCirc; early infant male circumcision; Botswana; neonatal; HIV; prevention ID NEONATAL MALE CIRCUMCISION; HIV PREVENTION; RANDOMIZED-TRIAL; PLASTIBELL; NEWBORN; COMPLICATIONS; INJURIES; AFRICA; CLAMP; MEN AB Existing devices for early infant male circumcision (EIMC) have inherent limitations. We evaluated the newly developed AccuCirc device by circumcising 151 clinically well, full-term male infants with birth weight >= 2.5 kg within the first 10 days of life from a convenience sample in 2 hospitals in Botswana. No major adverse events were observed. There was 1 local infection, 5 cases of minor bleeding, and 1 case of moderate bleeding. In 3 cases, the device made only partial incisions that were completed immediately by the provider without complications. Parental satisfaction was high: >96% of mothers stated that they would circumcise a future son. The pre-assembled, sterile AccuCirc kit has the potential to overcome obstacles related to supply chain management and on-site instrument disinfection that can pose challenges in resource-limited settings. In our study, the AccuCirc was safe and it should be considered for programmatic EIMC in resource-limited settings. C1 [Plank, Rebeca M.; Lockman, Shahin] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Wirth, Kathleen E.; Powis, Kathleen M.; Shapiro, Roger; Lockman, Shahin] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Plank, Rebeca M.; Wirth, Kathleen E.; Abdullahi, Rasak; Nkgau, Maggie; Powis, Kathleen M.; Mmalane, Mompati; Makhema, Joseph; Shapiro, Roger; Lockman, Shahin] Botswana Harvard Sch Publ Hlth AIDS Initiat Partn, Gaborone, Botswana. [Wirth, Kathleen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ndubuka, Nnamdi O.] Northern InterTribal Hlth Author, Prince Albert, SK, Canada. [Lesetedi, Chiapo] Botswana Minist Hlth, Gaborne, Botswana. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Shapiro, Roger] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Plank, RM (reprint author), Brigham & Womens Hosp, Dept Med, Div Infect Dis, 15 Francis St,PBB A-4, Boston, MA 02115 USA. EM rplank@partners.org FU National Institute of Health [K23 AI084579]; [U2GPS000941] FX Supported by Grant U2GPS000941; the National Institute of Health Grant K23 AI084579. NR 29 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2014 VL 66 IS 1 BP 1 EP 6 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4YF UT WOS:000337685400006 PM 24594500 ER PT J AU Bachhuber, MA Southern, WN Cunningham, CO AF Bachhuber, Marcus A. Southern, William N. Cunningham, Chinazo O. TI Profiting and Providing Less Care Comprehensive Services at For-Profit, Nonprofit, and Public Opioid Treatment Programs in the United States SO MEDICAL CARE LA English DT Article DE drug abuse; mental health; social services; infectious disease; health care organization ID SUBSTANCE-ABUSE TREATMENT; INJECTION-DRUG USERS; MAINTENANCE TREATMENT PROGRAMS; METHADONE-MAINTAINED PATIENTS; PSYCHIATRIC COMORBIDITY; HEPATITIS-C; PSYCHOSOCIAL SERVICES; HIV-INFECTION; MEDICAL-CARE; PREVENTION AB Background:Opioid use disorders are frequently associated with medical and psychiatric comorbidities (eg, HIV infection and depression), as well as social problems (eg, lack of health insurance). Comprehensive services addressing these conditions improve outcomes.Objective:To compare the proportion of for-profit, nonprofit, and public opioid treatment programs offering comprehensive services, which are not mandated by government regulations.Design, Setting, and Participants:Cross-sectional analysis of opioid treatment programs offering outpatient care in the United States (n=1036).Main Outcome Measure:Self-reported offering of communicable disease (HIV, sexually transmitted infections, and viral hepatitis) testing, psychiatric services (screening, assessment and diagnostic evaluation, and pharmacotherapy), and social services support (assistance in applying for programs such as Medicaid). Mixed-effects logistic regression models were developed to adjust for several county-level factors.Results:Of opioid treatment programs, 58.0% were for profit, 33.5% were nonprofit, and 8.5% were public. Nonprofit programs were more likely than for-profit programs to offer testing for all communicable diseases [adjusted odds ratios (AOR), 1.7; 95% confidence interval (CI), 1.2, 2.5], all psychiatric services (AOR, 8.0; 95% CI, 4.9, 13.1), and social services support (AOR, 3.3; 95% CI, 2.3, 4.8). Public programs were also more likely than for-profit programs to offer communicable disease testing (AOR, 6.4; 95% CI, 3.5, 11.7), all psychiatric services (AOR, 25.8; 95% CI, 12.6, 52.5), and social services support (AOR, 2.4; 95% CI, 1.4, 4.3).Conclusions:For-profit programs were significantly less likely than nonprofit and public programs to offer comprehensive services. Interventions to increase the offering of comprehensive services are needed, particularly among for-profit programs. C1 [Bachhuber, Marcus A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Bachhuber, Marcus A.] Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA USA. [Bachhuber, Marcus A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Southern, William N.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Hosp Med, Bronx, NY 10467 USA. [Cunningham, Chinazo O.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Gen Internal Med, Bronx, NY 10467 USA. RP Bachhuber, MA (reprint author), 1303-A Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM marcus.bachhuber@gmail.com OI Bachhuber, Marcus/0000-0002-5610-8382 FU NIH [R34DA031066, R01DA032110, R25DA023021]; Center for AIDS Research at the Albert Einstein College of Medicine; Montefiore Medical Center [NIH AI-51519] FX Supported by NIH R34DA031066, R01DA032110, R25DA023021, and the Center for AIDS Research at the Albert Einstein College of Medicine and Montefiore Medical Center (NIH AI-51519). NR 52 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD MAY PY 2014 VL 52 IS 5 BP 428 EP 434 DI 10.1097/MLR.0000000000000121 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ0BB UT WOS:000337312800009 PM 24638120 ER PT J AU Gabrielian, S Yuan, AH Andersen, RM Rubenstein, LV Gelberg, L AF Gabrielian, Sonya Yuan, Anita H. Andersen, Ronald M. Rubenstein, Lisa V. Gelberg, Lillian TI VA Health Service Utilization for Homeless and Low-income Veterans A Spotlight on the VA Supportive Housing (VASH) Program in Greater Los Angeles SO MEDICAL CARE LA English DT Article DE veterans; homelessness; supportive housing ID ANDERSEN BEHAVIORAL-MODEL; MENTAL-ILLNESS; MEDICAL-CARE; VULNERABLE POPULATIONS; EMERGENCY-DEPARTMENT; PUBLIC-HEALTH; ACCESS; WOMEN; 1ST; INDIVIDUALS AB Background:The US Department of Housing and Urban Development (HUD)-VA Supportive Housing (VASH) programthe VA's Housing First effortis central to efforts to end Veteran homelessness. Yet, little is known about health care utilization patterns associated with achieving HUD-VASH housing.Objectives:We compare health service utilization at the VA Greater Los Angeles among: (1) formerly homeless Veterans housed through HUD-VASH (HUD-VASH Veterans); (2) currently homeless Veterans; (3) housed, low-income Veterans not in HUD-VASH; and (4) housed, not low-income Veterans.Research Design:We performed a secondary database analysis of Veterans (n=62,459) who received VA Greater Los Angeles care between October 1, 2010 and September 30, 2011. We described medical/surgical and mental health utilization [inpatient, outpatient, and emergency department (ED)]. We controlled for demographics, need, and primary care use in regression analyses of utilization data by housing and income status.Results:HUD-VASH Veterans had more inpatient, outpatient, and ED use than currently homeless Veterans. Adjusting for demographics and need, HUD-VASH Veterans and the low-income housed Veterans had similar likelihoods of medical/surgical inpatient and outpatient utilization, compared with the housed, not low-income group. Adjusting first for demographics and need (model 1), then also for primary care use (model 2), HUD-VASH Veterans had the greatest decrease in incident rates of specialty medical/surgical, mental health, and ED care from models 1 to 2, becoming similar to the currently homeless, compared with the housed, not low-income group.Conclusions:Our findings suggest that currently homeless Veterans underuse health care relative to housed Veterans. HUD-VASH may address this disparity by providing housing and linkages to primary care. C1 [Gabrielian, Sonya] VA Greater Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Gabrielian, Sonya] VA Greater Los Angeles, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Gabrielian, Sonya; Yuan, Anita H.; Andersen, Ronald M.; Rubenstein, Lisa V.; Gelberg, Lillian] VA Greater Los Angeles, Hlth Serv Res & Dev Ctr Excellence Study Healthca, Los Angeles, CA USA. [Gabrielian, Sonya] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Yuan, Anita H.] Univ Calif Los Angeles, Vet Emergency Management Evaluat Ctr, Los Angeles, CA USA. [Andersen, Ronald M.; Gelberg, Lillian] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] VA Greater Los Angeles, Dept Med, Los Angeles, CA USA. [Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Gelberg, Lillian] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. RP Gabrielian, S (reprint author), WLA, VA Greater Los Angeles, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. EM sonya.gabrielian@va.gov FU Locally Initiated Project Grant from the Health Services Research & Development Center of Excellence for the Study of Healthcare Provider Behavior at the VA Greater Los Angeles [LIP 65-029]; VA Office of Patient Care Services; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs; Veterans Emergency Management Evaluation Center (VEMEC); Office of Academic Affiliations, Advanced Fellowship Program in Health Services Research, Department of Veterans Affairs [TPP 65-013]; NIDA [DA 022445]; UCLA/Drew Project EXPORT, National Center on Minority Health and Health Disparities [P20MD000148/P20MD000182]; VAIL-PCC [XVA 650-18] FX Supported by a Locally Initiated Project Grant from the Health Services Research & Development Center of Excellence for the Study of Healthcare Provider Behavior at the VA Greater Los Angeles (LIP 65-029). In part, this work was undertaken through the Veterans Administration's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. S. G. was supported in part by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs. A.H.Y. was supported by the Veterans Emergency Management Evaluation Center (VEMEC) and the Office of Academic Affiliations, Advanced Fellowship Program in Health Services Research, Department of Veterans Affairs (TPP 65-013). L. G. and R. M. A. were supported in part by NIDA DA 022445. R. M. A. received additional support from the UCLA/Drew Project EXPORT, National Center on Minority Health and Health Disparities, P20MD000148/P20MD000182. L. R. was supported in part by VAIL-PCC (XVA 650-18). NR 48 TC 4 Z9 4 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD MAY PY 2014 VL 52 IS 5 BP 454 EP 461 DI 10.1097/MLR.0000000000000112 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ0BB UT WOS:000337312800014 PM 24714583 ER PT J AU Ahmed, SG Taherian, M Prabhakar, S Hadaegh, F Qu, DM Sena-Esteves, M Fulci, G Eld, XOB Brenner, GJ AF Ahmed, Sherif G. Taherian, Mehran Prabhakar, Shilpa Hadaegh, Farnaz Qu, Dongmei Sena-Esteves, Miguel Fulci, Giulia Eld, Xandra O. Breakefi Brenner, Gary J. TI Mechanisms of Caspase-1 Mediated Schwannoma Regression SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Ahmed, Sherif G.; Taherian, Mehran; Hadaegh, Farnaz; Qu, Dongmei; Brenner, Gary J.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Prabhakar, Shilpa; Eld, Xandra O. Breakefi] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Fulci, Giulia] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Dept Neurol, Worcester, MA 01605 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Gene Therapy Ctr, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 777 BP S300 EP S300 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300768 ER PT J AU Angstman, JF Tsai, SQ Joung, K AF Angstman, James F. Tsai, Shengdar Q. Joung, Keith TI Extending Targeted DNA Demethylation Studies SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Angstman, James F.] Harvard Univ, Cambridge, MA 02138 USA. [Angstman, James F.; Tsai, Shengdar Q.; Joung, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 756 BP S292 EP S292 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300747 ER PT J AU Fitzpatrick, Z Mu, DK Maguire, CA AF Fitzpatrick, Zachary Mu, Dakai Maguire, Casey A. TI Vesicle-Cloaked AAV Resists Neutralizing Antibodies In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Fitzpatrick, Zachary; Mu, Dakai; Maguire, Casey A.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 60 BP S23 EP S23 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300060 ER PT J AU Fu, YF Sander, J Reyon, D Cascio, V Joung, K AF Fu, Yanfang Sander, Jeffry Reyon, Deepak Cascio, Vincent Joung, Keith TI Improving the Specificities of CRISPR-Cas9 Nucleases Using Truncated Guide RNAs in Human Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Fu, Yanfang; Sander, Jeffry; Reyon, Deepak; Cascio, Vincent; Joung, Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Fu, Yanfang; Sander, Jeffry; Reyon, Deepak; Cascio, Vincent; Joung, Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Fu, Yanfang; Sander, Jeffry; Reyon, Deepak; Cascio, Vincent; Joung, Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Fu, Yanfang; Sander, Jeffry; Reyon, Deepak; Joung, Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 244 BP S93 EP S93 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300244 ER PT J AU Guda, S Peng, D Bauer, DE Renella, R Kamran, SC Thornton, J Brendel, C De Boer, H Milsom, MD Orkin, SH Gregory, R Williams, DA AF Guda, Swaroopa Peng, Du Bauer, Daniel E. Renella, Raffaele Kamran, Sophia C. Thornton, James Brendel, Christian De Boer, Helen Milsom, Michael D. Orkin, Stuart H. Gregory, Richard Williams, David A. TI Optimization of Lentivirus Vector RNA Polymerase II Driven microRNA Embedded shRNAs for Enhanced Processing and Efficient Knockdown of Bcl11a for Induction of Fetal Hemoglobin in Erythroid Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Guda, Swaroopa; Peng, Du; Bauer, Daniel E.; Renella, Raffaele; Thornton, James; Brendel, Christian; De Boer, Helen; Orkin, Stuart H.; Gregory, Richard; Williams, David A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Bauer, Daniel E.; Renella, Raffaele; Orkin, Stuart H.; Williams, David A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bauer, Daniel E.; Kamran, Sophia C.; Orkin, Stuart H.; Williams, David A.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Peng, Du; Thornton, James; Gregory, Richard] Boston Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Milsom, Michael D.] Heidelberg Inst Stem Cell Technol & Expt Med, Div Stem Cells & Canc, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 532 BP S207 EP S207 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300527 ER PT J AU Gyorgy, B Fitzpatrick, Z Mu, DK Maguire, CA AF Gyorgy, Bence Fitzpatrick, Zachary Mu, Dakai Maguire, Casey A. TI A system for Rapid Retargeting of AAV In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Gyorgy, Bence; Fitzpatrick, Zachary; Mu, Dakai; Maguire, Casey A.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 296 BP S114 EP S114 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300296 ER PT J AU Gyorgy, B Fitzpatrick, Z Mu, DK Maguire, CA AF Gyorgy, Bence Fitzpatrick, Zachary Mu, Dakai Maguire, Casey A. TI Enhancing AAV9 Transduction and Multi-Capsid Packaging Using Extracellular Vesicles SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Gyorgy, Bence; Fitzpatrick, Zachary; Mu, Dakai; Maguire, Casey A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 297 BP S114 EP S114 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300297 ER PT J AU Hanley, PJ Nikiforow, S Heslop, HE Shpall, EJ Barrett, J Rodgers, J Bollard, C AF Hanley, Patrick J. Nikiforow, Sarah Heslop, Helen E. Shpall, E. J. Barrett, John Rodgers, John Bollard, Catherine TI CMV-Specific T Cells Derived From the Naive T Cell Population To Treat Transplant Recipients SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Hanley, Patrick J.; Bollard, Catherine] Childrens Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Washington, DC USA. [Nikiforow, Sarah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Heslop, Helen E.; Rodgers, John] Baylor Coll Med, CAGT, Houston, TX 77030 USA. [Barrett, John] NHLBI, NIH, Bethesda, MD 20892 USA. [Shpall, E. J.] MD Anderson, Stem Cell Transplantat, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 693 BP S268 EP S268 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300684 ER PT J AU Khaychuk, V Zinn, E Plovie, E Sarkar, D Carvalho, L Shah, S Vandenberghe, LH AF Khaychuk, Vadim Zinn, Eric Plovie, Eva Sarkar, Debalina Carvalho, Livia Shah, Samiksha Vandenberghe, Luk H. TI Enhanced Liver Transduction With Novel AAV Resistant To Pre-Existing Immunity in Humans SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Khaychuk, Vadim; Zinn, Eric; Plovie, Eva; Sarkar, Debalina; Carvalho, Livia; Shah, Samiksha; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 581 BP S225 EP S225 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300575 ER PT J AU Ning, JF Wakimoto, H Martuza, RL Rabkin, SD AF Ning, Jianfang Wakimoto, Hiroaki Martuza, Robert L. Rabkin, Samuel D. TI Targeting Glioblastoma Stem Cells with Oncolytic HSV and PARP Inhibitors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Ning, Jianfang; Martuza, Robert L.; Rabkin, Samuel D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ning, Jianfang; Martuza, Robert L.; Rabkin, Samuel D.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 178 BP S68 EP S68 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300178 ER PT J AU Rahman, SH Kuehle, J Reimann, C Maeder, ML Riedel, H Fisch, P Cantz, T Rudolph, C Joung, KJ Schambach, A Cathomen, T AF Rahman, Shamim H. Kuehle, Johannes Reimann, Christian Maeder, Morgan L. Riedel, Heimo Fisch, Paul Cantz, Tobias Rudolph, Cornelia Joung, Keith J. Schambach, Axel Cathomen, Toni TI Designer Nuclease-Mediated Correction of RS-SCID SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Rahman, Shamim H.; Reimann, Christian; Cathomen, Toni] Univ Med Ctr Freiburg, Inst Cell & Gene Therapy, Freiburg, Germany. [Rahman, Shamim H.; Reimann, Christian; Cathomen, Toni] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Rahman, Shamim H.; Kuehle, Johannes; Schambach, Axel; Cathomen, Toni] Hannover Med Sch, Inst Expt Hematol, Hannover, Germany. [Maeder, Morgan L.; Joung, Keith J.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Riedel, Heimo] W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA. [Fisch, Paul] Univ Med Ctr Freiburg, Inst Pathol, Freiburg, Germany. [Cantz, Tobias] Hannover Med Sch, REBIRTH, JRG Stem Cell Biol, Hannover, Germany. [Rudolph, Cornelia] Hannover Med Sch, Inst Cellular & Mol Pathol, Hannover, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 91 BP S34 EP S34 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300091 ER PT J AU Sarkar, D Plovie, E Zinn, E Khaychuk, V Carvalho, L Vandenberghe, LH AF Sarkar, Debalina Plovie, Eva Zinn, Eric Khaychuk, Vadim Carvalho, Livia Vandenberghe, Luk H. TI Seroprevalence Assessment of Novel, Ancestrally Derived AAV Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Sarkar, Debalina; Plovie, Eva; Zinn, Eric; Khaychuk, Vadim; Carvalho, Livia; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 194 BP S74 EP S74 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300194 ER PT J AU Teng, J Hejazi, S Badr, CE Tannous, BA AF Teng, Jian Hejazi, Seyedali Badr, Christian E. Tannous, Bakhos A. TI Systemic Injection of Human Neural Stem Cells Expressing an Anti-Cancer Agent Targets Invasive Gliomas and Induces Tumor Regression in Combination With a Cardiac Glycoside as Monitored By a Secreted Blood Reporter SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Teng, Jian; Hejazi, Seyedali; Badr, Christian E.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. [Teng, Jian; Hejazi, Seyedali; Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 271 BP S104 EP S104 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300271 ER PT J AU Tsai, SQ Wyvekens, N Foden, JA Khayter, C Cascio, VM Joung, JK AF Tsai, Shengdar Q. Wyvekens, Nicolas Foden, Jennifer A. Khayter, Cyd Cascio, Vincent M. Joung, J. Keith TI Expanded Specificity Profiles of CRISPR/Cas9 RNA-Guided Nucleases in Human Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Tsai, Shengdar Q.; Wyvekens, Nicolas; Foden, Jennifer A.; Khayter, Cyd; Cascio, Vincent M.; Joung, J. Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsai, Shengdar Q.; Joung, J. Keith] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 326 BP S125 EP S125 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300325 ER PT J AU Turunen, HT Xiao, R Plovie-Buys, E Vandenberghe, LH AF Turunen, Heikki T. Xiao, Ru Plovie-Buys, Eva Vandenberghe, Luk H. TI Development of a qPCR Based Assay for Assessing Integrity of Oversized AAV Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Turunen, Heikki T.; Xiao, Ru; Plovie-Buys, Eva; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Gene Transfer Vector Core,Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 305 BP S117 EP S118 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300305 ER PT J AU Turunen, HT Vandenberghe, LH AF Turunen, Heikki T. Vandenberghe, Luk H. TI Generating Novel AAV Capsid Mutants for Large Genome Packaging Through Protein Libraries and Directed Evolution SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Turunen, Heikki T.; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 306 BP S118 EP S118 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300306 ER PT J AU Dubach, JM Vinegoni, C Mazitschek, R Feruglio, PF Cameron, LA Weissleder, R AF Dubach, J. M. Vinegoni, C. Mazitschek, R. Feruglio, P. Fumene Cameron, L. A. Weissleder, R. TI In vivo imaging of specific drug-target binding at subcellular resolution SO NATURE COMMUNICATIONS LA English DT Article ID POLARIZED FLUORESCENCE MICROSCOPY; GPI-ANCHORED PROTEINS; LIVING CELLS; SINGLE-CELL; LIVE CELLS; ANISOTROPY; ENGAGEMENT; ORGANIZATION; INHIBITION; INSIGHTS AB The possibility of measuring binding of small-molecule drugs to desired targets in live cells could provide a better understanding of drug action. However, current approaches mostly yield static data, require lysis or rely on indirect assays and thus often provide an incomplete understanding of drug action. Here, we present a multiphoton fluorescence anisotropy microscopy live cell imaging technique to measure and map drug-target interaction in real time at subcellular resolution. This approach is generally applicable using any fluorescently labelled drug and enables high-resolution spatial and temporal mapping of bound and unbound drug distribution. To illustrate our approach we measure intracellular target engagement of the chemotherapeutic Olaparib, a poly(ADP-ribose) polymerase inhibitor, in live cells and within a tumour in vivo. These results are the first generalizable approach to directly measure drug-target binding in vivo and present a promising tool to enhance understanding of drug activity. C1 [Dubach, J. M.; Vinegoni, C.; Mazitschek, R.; Feruglio, P. Fumene; Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Dubach, J. M.; Vinegoni, C.; Mazitschek, R.; Feruglio, P. Fumene; Weissleder, R.] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Cameron, L. A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu FU Federal funds from the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000044C]; National Cancer Institute [T32CA079443, P50CA086355]; Institute of Biomedical Engineering [R01EB006432]; [1R01CA164448-01] FX This project was funded in part by Federal funds from the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services (under Contract No. HHSN268201000044C), National Cancer Institute (T32CA079443 and P50CA086355), and from the Institute of Biomedical Engineering (under R01EB006432), and in part by 1R01CA164448-01. NR 39 TC 11 Z9 11 U1 5 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2014 VL 5 AR 3946 DI 10.1038/ncomms4946 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AJ2QZ UT WOS:000337505600005 PM 24867710 ER PT J AU Mehta, SN Volkening, LK Quinn, N Laffel, LMB AF Mehta, Sanjeev N. Volkening, Lisa K. Quinn, Nicolle Laffel, Lori M. B. TI Intensively managed young children with type 1 diabetes consume high-fat, low-fiber diets similar to age-matched controls SO NUTRITION RESEARCH LA English DT Article DE Diabetes mellitus; Type 1; Nutrition; Pediatrics; Childhood obesity; Cross-sectional analysis ID PRESCHOOL-CHILDREN; GLUCOSE CONTROL; ADOLESCENTS; YOUTH; PREVALENCE; RECALL; COMPLICATIONS; OVERWEIGHT; ADHERENCE; BEHAVIORS AB Despite significant emphasis on nutrition, older children with diabetes demonstrate poor dietary quality. We tested the hypothesis that dietary quality in young children with type 1 diabetes (T1D) would be better than age-matched children in the US population. Dietary data from children with T1D (n = 67) aged 2 to 12 years attending a pediatric diabetes clinic were compared with a nationally representative, age-matched sample from the National Health and Nutrition Examination Survey (NHANES; n = 1691). Multiple 24-hour dietary recalls were used. Recommended intakes were based on national guidelines, and dietary quality was assessed using the Healthy Eating Index-2005. More children with T1D were overweight or obese compared with children participating in NHANES (42% vs 30%, P =.04). Greater proportions of children with T1D met daily recommendations for vegetables (22% vs 13%, P =.03), whole grains (12% vs 5%, P =.005), and dairy (55% vs 36%, P =.001) compared with NHANES children, whereas similar proportions met daily fruit recommendations (40% vs 33%, P =.2). Less than one-third of all children limited total fat to recommended levels; children with T1D consumed more saturated fat than did NHANES children (14% vs 12% total energy intake, P =.0009). Fiber intakes were very low in both groups. Compared with NHANES children, children with T1D had higher Healthy Eating Index-2005 scores (59.6 vs 49.7, P =.0006) primarily because of lower intakes of added sugars. The nutritional intake of young children with T1D remains suboptimal in the contemporary era of diabetes management. Despite focused nutrition management, young children with T1D consume high-fat, low-fiber diets comparable with youth in the general population. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mehta, Sanjeev N.; Volkening, Lisa K.; Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Quinn, Nicolle] Boston Childrens Hosp, Clin Translat Study Unit, Boston, MA USA. RP Mehta, SN (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, One Joslin Pl, Boston, MA 02215 USA. EM sanjeev.mehta@joslin.harvard.edu FU National Institute of Health Career Development Grant in Pediatric Endocrinology [K12 DK6396-05]; Eli Lilly Foundation Fellowship Training Grant; Harvard Pediatric Health Services Research Fellowship [HRSA T32 HP10018-12]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Fund FX This study was supported by a National Institute of Health Career Development Grant in Pediatric Endocrinology (K12 DK6396-05), an Eli Lilly Foundation Fellowship Training Grant, the Harvard Pediatric Health Services Research Fellowship (HRSA T32 HP10018-12), the Katherine Adler Astrove Youth Education Fund, and the Maria Griffin Drury Fund. Portions of this manuscript were presented at the 68th Scientific Sessions of the American Diabetes Association (2008). The authors declare that they have no competing interests. NR 31 TC 6 Z9 6 U1 4 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 2014 VL 34 IS 5 BP 428 EP 435 DI 10.1016/j.nutres.2014.04.008 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AJ5IK UT WOS:000337715700007 PM 24916556 ER PT J AU Charles, RC Hilaire, IJ Mayo-Smith, LM Teng, JE Jerome, JG Franke, MF Saha, A Yu, YN Kovac, P Calderwood, SB Ryan, ET LaRocque, RC Almazor, CP Qadri, F Ivers, LC Harris, JB AF Charles, Richelle C. Hilaire, Isabelle J. Mayo-Smith, Leslie M. Teng, Jessica E. Jerome, J. Gregory Franke, Molly F. Saha, Amit Yu, Yanan Kovac, Paul Calderwood, Stephen B. Ryan, Edward T. LaRocque, Regina C. Almazor, Charles P. Qadri, Firdausi Ivers, Louise C. Harris, Jason B. TI Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID FIELD-TRIAL; BLOOD-GROUP; BANGLADESH; RESPONSES; ANTIBODY; CHILDREN; INFECTION; EFFICACY; ANTIGEN; SPECIFICITY AB Background: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae. Methodology/Principal Findings: We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-17 years), and 47 younger children (1-5 years) in Haiti, where cholera was introduced in 2010. A >= 4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A >= 2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age-and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine. Conclusions/Significance: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae. C1 [Charles, Richelle C.; Mayo-Smith, Leslie M.; Yu, Yanan; Calderwood, Stephen B.; Ryan, Edward T.; LaRocque, Regina C.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.; LaRocque, Regina C.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hilaire, Isabelle J.; Teng, Jessica E.; Jerome, J. Gregory; Franke, Molly F.; Almazor, Charles P.; Ivers, Louise C.] Partners Hlth, Boston, MA USA. [Teng, Jessica E.; Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Franke, Molly F.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Saha, Amit; Qadri, Firdausi] Icddr B, Dhaka, Bangladesh. [Kovac, Paul] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM rccharles@mgh.harvard.edu; livers@pih.org; jbharris@mgh.harvard.edu FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [R01 AI099243, AI077883, AI058935, AI106878, K08 AI089721]; Bill and Melinda Gates Foundation [OPP50419]; Massachusetts General Hospital Physician Scientist Development Award from Massachusetts General Hospital FX This work was supported by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (R01 AI099243; JBH, LCI), (AI077883, AI058935, AI106878 ETR), and the Career Development Award (K08 AI089721; RCC); the Bill and Melinda Gates Foundation (OPP50419; FQ); and a Massachusetts General Hospital Physician Scientist Development Award from Massachusetts General Hospital (RCC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 12 Z9 12 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2014 VL 8 IS 5 AR e2828 DI 10.1371/journal.pntd.0002828 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ5OS UT WOS:000337735100025 PM 24786645 ER PT J AU Fidler, R Hirsch, J Stechert, M Johnson, M AF Fidler, Richard Hirsch, Jan Stechert, Martin Johnson, Meshell TI Three modes of cardiac compressions in a single patient: A comparison of usual manual compressions, automated compressions, and open cardiac massage SO RESUSCITATION LA English DT Letter ID CARDIOPULMONARY-RESUSCITATION; ARREST C1 [Fidler, Richard; Hirsch, Jan; Stechert, Martin] Univ Calif San Francisco, Dept Anesthesia, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Johnson, Meshell] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA USA. RP Fidler, R (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Anesthesiol 129, San Francisco, CA 94121 USA. EM richard.fidler@ucsf.edu OI Fidler, Richard/0000-0003-4358-7887 NR 5 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2014 VL 85 IS 5 BP E75 EP E76 DI 10.1016/j.resuscitation.2014.01.010 PG 2 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA AJ0GX UT WOS:000337329500005 PM 24447422 ER PT J AU Lehmen, JA Deering, RM Simpson, AK Carrier, CS Bono, CM AF Lehmen, Jeff A. Deering, Rachel M. Simpson, Andrew K. Carrier, Charles S. Bono, Christopher M. TI Inconsistencies Between Abstracts and Manuscripts in Published Studies About Lumbar Spine Surgery SO SPINE LA English DT Review DE randomized controlled trials; lumbar spine surgery; abstracts; accuracy ID RESEARCH ARTICLES; ACCURACY; JOURNALS; QUALITY; TRIALS AB Study Design. Systematic review. Objective. To perform a comparison of randomized controlled trial (RCT) abstracts and manuscripts published in recent spinal literature. Summary of Background Data. RCTs represent the "gold standard" upon which evidence-based treatment decisions are made. Inconsistencies between an abstract and manuscript can mislead readers' interpretation of findings and conclusions. Abstract findings are often cited without reference to the manuscript itself. In other fields of medicine, studies have shown discrepancies between RCT abstracts and manuscripts. Methods. A literature search of RCTs published in Spine, The Spine Journal, and Journal of Spinal Disorders and Techniques during a 10year period (2001-2010) was performed. All manuscripts described as randomized trials concerning lumbar spinal surgery were selected. Manuscripts were analyzed using a standardized 21-item questionnaire to collect data regarding inconsistencies or bias in the abstract compared with the manuscript. Abstracts were considered deficient if they contained data that were either inconsistent with the manuscript or if they failed to include important findings from the manuscript. Four reviewers reported on the 40 manuscripts that met the inclusion criteria. Each manuscript was reviewed by 2 reviewers. In the event of conflicts in analysis, resolution was achieved through discussion between the reviewers. Results. At least 1 inconsistency was found in 75% of studies. Despite the word "randomized" appearing in 75% of titles and 92.5% of abstracts, the method of randomization was not described in 37.5% of manuscripts and ( if described) was considered unacceptable in 28%. The primary outcome of the study was clearly stated in only 22.5% of abstracts and 47.5% of manuscripts. Pertinent negatives were not reported in 40% of the abstracts. Relevant statistically significant results were reported in only 60% of abstracts. Conclusion. Abstracts are discrepant with full manuscripts in a surprisingly high proportion of manuscripts. Authors, editors, and peer reviewers should strive to ensure that abstracts accurately represent the data in RCT manuscripts. C1 [Lehmen, Jeff A.; Deering, Rachel M.; Simpson, Andrew K.; Bono, Christopher M.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Lehmen, Jeff A.; Simpson, Andrew K.; Carrier, Charles S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Carrier, Charles S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Carrier, CS (reprint author), Tufts Univ, Sch Med, 145 Harrison Ave, Boston, MA 02111 USA. EM Charles.s.carrier@gmail.com NR 10 TC 0 Z9 0 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD MAY 1 PY 2014 VL 39 IS 10 BP 841 EP 845 DI 10.1097/BRS.0000000000000290 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AJ1YR UT WOS:000337452400019 PM 24583735 ER PT J AU Osler, P Kim, SD Hess, KA Phan, P Simpson, AK Mansfield, FL Berger, D Craveiro, VL Wood, KB AF Osler, Polina Kim, Sang D. Hess, Kathryn A. Phan, Philippe Simpson, Andrew K. Mansfield, Frederick L. Berger, David Craveiro, Vinicius Ladeira Wood, Kirkham B. TI Prior Abdominal Surgery Is Associated With an Increased Risk of Postoperative Complications After Anterior Lumbar Interbody Fusion SO SPINE LA English DT Article DE retroperitoneal approach; anterior approach to spine; perioperative complications; anterior lumbar interbody fusion; ALIF ID BONE MORPHOGENETIC PROTEIN-2; RETROPERITONEAL EXPOSURE; SPINE AB Study Design. Retrospective medical record review. Objective. The purpose of this study was to determine whether a history of abdominal/pelvic surgery confers an increased risk of retroperitoneal anterior approach-related complications when undergoing anterior lumbar interbody fusion. Summary of Background Data. As anterior lumbar interbody fusion gains popularity, both anterior retroperitoneal approach have become increasingly used. Methods. The records of 263 patients, who underwent infraumbilical retroperitoneal approach to the anterior aspect of the lower lumbar spine for a degenerative spine condition between 2007 and 2011 were retrospectively reviewed. Patient's demographics, risk factors, preoperative diagnosis, surgical history, level of the anterior fusion, and perioperative complications were collected. Anterior retroperitoneal approach to the spine was carried out by a single general surgeon. Results. Ninety-seven patients (37%) developed at least 1 complication. Forty-nine percent of patients with a history of abdominal surgery developed a postoperative complication compared with 28% of patients without such history (RR = 1.747, P <= 0.001). After controlling for other factors such as age, sex, body mass index, diagnostic groups, and preoperative comorbidities (hypertension, diabetes, and smoking status), these differences remained statistically significant. When each type of complication was considered separately, there was a statistically significant difference in the incidence of general complications (RR = 2.384, P = 0.007), instrumentation-related complications (RR = 2.954, P = 0.010), and complications related to the anterior approach (RR = 1.797, P = 0.021). Conclusion. Anterior lumbar interbody fusion via a midline incision and a retroperitoneal approach was associated with 37% overall rate of complication. Patients with a history of abdominal or pelvic surgery are at a higher risk of developing general, instrumentation, and anterior approach-related complications. C1 [Osler, Polina; Hess, Kathryn A.; Phan, Philippe; Simpson, Andrew K.; Mansfield, Frederick L.; Berger, David; Craveiro, Vinicius Ladeira; Wood, Kirkham B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Osler, Polina; Phan, Philippe; Simpson, Andrew K.; Mansfield, Frederick L.; Wood, Kirkham B.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Sang D.] Washington Univ Orthopaed, St Louis, MO USA. [Berger, David] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Osler, P (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey Ste 3A, Boston, MA 02114 USA. EM posler@partners.org NR 13 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD MAY 1 PY 2014 VL 39 IS 10 BP E650 EP E656 DI 10.1097/BRS.0000000000000293 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AJ1YR UT WOS:000337452400008 PM 24583724 ER PT J AU Lai, YY Dilidaer, D Chen, B Xu, G Shi, JB Lee, RJ Cohen, NA AF Lai, Yinyan Dilidaer, D. Chen, Bei Xu, Geng Shi, Jianbo Lee, Robert J. Cohen, Noam A. TI In vitro studies of a distillate of rectified essential oils on sinonasal components of mucociliary clearance SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID CILIARY BEAT FREQUENCY; UPPER RESPIRATORY-INFECTION; CHRONIC RHINOSINUSITIS; FLUID SECRETION; TRANSPORT; CILIOGENESIS; T2R38 AB Background: Herbal remedies predate written history and continue to be used frequently for many common ailments. The essential oil mixture standardized is a phytopharmaceutical with a distillate of a mixture of rectified essential oils of eucalyptus, sweet orange, myrtle, and lemon as active ingredients used to treat respiratory diseases such as bronchitis and rhinosinusitis. We evaluated the pharmacologic effects of a distillate of rectified essential oils standardized on primary human upper respiratory epithelial cultures specifically addressing electrolyte transport, cilia beat frequency (CBF), airway surface liquid (ASL) hydration, and mucus transport velocity. Methods: Well-differentiated primary human sinonasal epithelial cultures grown at an air-liquid interface were treated on the apical or basolateral surface with varying concentrations of a distillate of rectified essential oils standardized. Changes in CBF were determined using the Sissons-Ammons Video Analysis system while changes in chloride flux were determined using the fluorescent dye 6-methoxy-N-(3-sulfopropyl) quinolinium. ASL hydration was quantified using Texas red dextran and mucociliary transport velocity was measured using fluorescent microspheres and time lapse photography. Results: When applied to the basolateral surface, a distillate of rectified essential oils standardized activated chloride efflux and ciliary beat in a dose-dependent fashion, increasing ASL height and accelerating mucociliary transport velocity. The ancillary apical application of a distillate of rectified essential oils standardized had minimal effects on the CBF. Conclusion: Basolateral application of a distillate of rectified essential oils standardized stimulates both chloride efflux and cilia beat frequency resulting in a synergistic effect dramatically augmenting mucociliary transport velocity. These in vitro data support the clinical efficacy of this phytopharmaceutical in respiratory inflammatory disorders. C1 [Lai, Yinyan; Dilidaer, D.; Chen, Bei; Lee, Robert J.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Lai, Yinyan; Dilidaer, D.; Xu, Geng; Shi, Jianbo; Cohen, Noam A.] Sun Yat Sen Univ, Affiliated Hosp 1, Otorhinolaryngol Hosp, Guangzhou 510275, Guangdong, Peoples R China. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Div Otolaryngol, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Div Rhinol, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU G. Pohl Boskamp, Hohenlockstedt, Germany FX Funded by G. Pohl Boskamp, Hohenlockstedt, Germany NR 20 TC 4 Z9 6 U1 2 U2 9 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAY-JUN PY 2014 VL 28 IS 3 BP 244 EP 248 DI 10.2500/ajra.2014.28.4036 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA AI9QY UT WOS:000337269100016 PM 24980236 ER PT J AU Weissman, SH Busch, KG Schouten, R AF Weissman, Sidney H. Busch, Kenneth G. Schouten, Ronald TI Introduction to this issue: The Evolution of Terrorism from 1914 to 2014 SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID PSYCHOLOGY; LOGIC C1 [Weissman, Sidney H.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Busch, Kenneth G.] Dept Hlth & Human Serv, Chicago, IL USA. [Schouten, Ronald] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Schouten, Ronald] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Busch, KG (reprint author), US Dept HHS, 30 N Michigan Ave,Suite 1916, Chicago, IL 60602 USA. EM kgbusch@sbcglobal.net NR 14 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0735-3936 EI 1099-0798 J9 BEHAV SCI LAW JI Behav. Sci. Law PD MAY-JUN PY 2014 VL 32 IS 3 SI SI BP 259 EP 262 DI 10.1002/bsl.2124 PG 4 WC Psychology, Applied; Law SC Psychology; Government & Law GA AJ2RT UT WOS:000337508800001 PM 24832491 ER PT J AU Matsumoto, H Murakami, Y Kataoka, K Lin, H Connor, KM Miller, JW Zhou, D Avruch, J Vavvas, DG AF Matsumoto, H. Murakami, Y. Kataoka, K. Lin, H. Connor, K. M. Miller, J. W. Zhou, D. Avruch, J. Vavvas, D. G. TI Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment SO CELL DEATH & DISEASE LA English DT Article DE retinal detachment photoreceptor cell; apoptosis; neurodegeneration; mammalian STE20-like kinase ID ORGAN SIZE CONTROL; YES-ASSOCIATED PROTEIN; SIGNALING PATHWAY; HIPPO PATHWAY; CONTACT INHIBITION; EXPERIMENTAL-MODEL; GROWTH-CONTROL; APOPTOSIS; YAP; MST2 AB Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and tumorigenesis. However, to date the role of MST in neurodegeneration has not been fully explored. Utilizing MST1(-/-) and MST2(-/-) mice we identified MST2, but not MST1, as a regulator of photoreceptor cell death in a mouse model of RD. MST2(-/-) mice demonstrated significantly decreased photoreceptor cell death and outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation was attenuated in MST2(-/-) mice compared to control mice after RD. The transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also reduced in MST2(-/-) mice post-RD. Retinas of MST2(-/-) mice displayed suppressed nuclear relocalization of phosphorylated YAP after RD. Consistent with the reduction of photoreceptor cell death, MST2(-/-) mice showed decreased levels of proinflammatory cytokines such as monocyte chemoattractant protein 1 and interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during the early phase of RD. These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target. C1 [Matsumoto, H.; Murakami, Y.; Kataoka, K.; Lin, H.; Connor, K. M.; Miller, J. W.; Vavvas, D. G.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Angiogenesis Lab,Retina Serv, Boston, MA 02114 USA. [Zhou, D.] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen 361102, Fujian, Peoples R China. [Avruch, J.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Angiogenesis Lab,Retina Serv, 325 Cambridge St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu RI Kataoka, Keiko/B-2806-2016; OI Kataoka, Keiko/0000-0002-8795-6536; Zhou, Dawang/0000-0002-9053-5249; Connor, Kip/0000-0002-2048-9080; Vavvas, Demetrios/0000-0002-8622-6478 FU Foundation Lions Eye Research Fund; Yeatts Family Foundation; Macula Society Research Grant award; Bausch & Lomb Vitreoretinal Fellowship; Special Scholar Award; Physician Scientist Award; Research to Prevent Blindness Foundation; NEI [R21EY023079-01/A1, EY014104]; NIH [R01EY022084-01/S1] FX This work was supported by Foundation Lions Eye Research Fund (DGV); The Yeatts Family Foundation (DGV, JWM); 2013 Macula Society Research Grant award (DGV); Bausch & Lomb Vitreoretinal Fellowship (HM); a Special Scholar Award (KMC), a Physician Scientist Award (DGV) and unrestricted grant (JWM) from the Research to Prevent Blindness Foundation; NEI R21EY023079-01/A1 (DGV), NIH R01EY022084-01/S1 (KMC) and NEI grant EY014104 (MEEI Core Grant). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health. NR 67 TC 9 Z9 9 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD MAY PY 2014 VL 5 SI SI AR e1269 DI 10.1038/cddis.2014.218 PG 9 WC Cell Biology SC Cell Biology GA AI9DN UT WOS:000337229300069 PM 24874741 ER PT J AU Xia, X Owen, MS Lee, REC Gaudet, S AF Xia, X. Owen, M. S. Lee, R. E. C. Gaudet, S. TI Cell-to-cell variability in cell death: can systems biology help us make sense of it all? SO CELL DEATH & DISEASE LA English DT Review DE cell-to-cell variability; computational modeling; signaling dynamics; apoptosis ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; RESONANCE ENERGY-TRANSFER; TUMOR-NECROSIS-FACTOR; INDUCED APOPTOSIS; SIGNALING NETWORKS; REGULATORY HETEROGENEITIES; CASPASE-3 ACTIVATION; ACQUIRED-RESISTANCE; SINGLE CELLS; CANCER AB One of the most common observations in cell death assays is that not all cells die at the same time, or at the same treatment dose. Here, using the perspective of the systems biology of apoptosis and the context of cancer treatment, we discuss possible sources of this cell-to-cell variability as well as its implications for quantitative measurements and computational models of cell death. Many different factors, both within and outside of the apoptosis signaling networks, have been correlated with the variable responses to various death-inducing treatments. Systems biology models offer us the opportunity to take a more synoptic view of the cell death process to identify multifactorial determinants of the cell death decision. Finally, with an eye toward 'systems pharmacology', we discuss how leveraging this new understanding should help us develop combination treatment strategies to compel cancer cells toward apoptosis by manipulating either the biochemical state of cancer cells or the dynamics of signal transduction. C1 [Xia, X.; Owen, M. S.; Lee, R. E. C.; Gaudet, S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Xia, X.; Owen, M. S.; Lee, R. E. C.; Gaudet, S.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Xia, X.; Owen, M. S.; Lee, R. E. C.; Gaudet, S.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. RP Gaudet, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol Genet, 450 Brookline Ave,Smith 836B, Boston, MA 02215 USA. EM Suzanne_gaudet@dfci.harvard.edu FU NIH [P01-CA139980, R01-GM104247]; Barr investigator award; Kimmel Scholar FX This work was funded by NIH grants P01-CA139980, R01-GM104247 and a Barr investigator award to SG. SG is a Kimmel Scholar and RECL is a CIHR research fellow. NR 79 TC 9 Z9 10 U1 1 U2 27 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 MAY PY 2014 VL 5 SI SI AR e1261 DI 10.1038/cddis.2014.199 PG 11 WC Cell Biology SC Cell Biology GA AI9DN UT WOS:000337229300061 PM 24874733 ER PT J AU Luxton, DD Pruitt, LD O'Brien, K Stanfill, K Jenkins-Guarnieri, MA Johnson, K Wagner, A Thomas, E Gahm, GA AF Luxton, David D. Pruitt, Larry D. O'Brien, Karen Stanfill, Katherine Jenkins-Guarnieri, Michael A. Johnson, Kristine Wagner, Amy Thomas, Elissa Gahm, Gregory A. TI Design and methodology of a randomized clinical trial of home-based telemental health treatment for US military personnel and veterans with depression SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Telemental health; Telehealth; Home-based; Depression; Military; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; BEHAVIORAL ACTIVATION; THERAPY; SCALE; NONINFERIORITY; OUTCOMES; PTSD AB Home-based telemental health (TMH) treatments have the potential to address current and future health needs of military service members, veterans, and their families, especially for those who live in rural or underserved areas. The use of home-based TMH treatments to address the behavioral health care needs of U.S. military healthcare beneficiaries is not presently considered standard of care in the Military Health System. The feasibility, safety, and clinical efficacy of home-based TMH treatments must be established before broad dissemination of home-based treatment programs can be implemented. This paper describes the design, methodology, and protocol of a clinical trial that compares in-office to home-based Behavioral Activation for Depression (BATD) treatment delivered via web-based video technology for service members and veterans with depression. This grant funded three-year randomized clinical trial is being conducted at the National Center for Telehealth and Technology at Joint-base Lewis-McChord and at the Portland VA Medical Center. Best practice recommendations regarding the implementation of in-home telehealth in the military setting as well as the cultural and contextual factors of providing in-home care to active duty and veteran military populations are also discussed. Published by Elsevier Inc. C1 [Luxton, David D.; Pruitt, Larry D.; O'Brien, Karen; Stanfill, Katherine; Jenkins-Guarnieri, Michael A.; Johnson, Kristine; Thomas, Elissa; Gahm, Gregory A.] Natl Ctr Telehealth & Technol, Tacoma, WA USA. [Luxton, David D.; Gahm, Gregory A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Wagner, Amy] Portland VA Med Ctr, Portland, OR USA. RP Luxton, DD (reprint author), Def Ctr Excellence Psychol Hlth & Traumat Brain I, Natl Ctr Telehealth & Technol T2, 9933 West Hayes St, Tacoma, WA 98431 USA. EM david.d.luxton.civ@mail.mil OI Pruitt, Larry/0000-0001-6925-7830 FU U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD [W81XWH-11-2-0118] FX This research grant was awarded and administered by the U.S. Army Medical Research & Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD (award # W81XWH-11-2-0118). The content of this information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. NR 39 TC 5 Z9 5 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2014 VL 38 IS 1 BP 134 EP 144 DI 10.1016/j.cct.2014.04.002 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AI8VA UT WOS:000337203900015 PM 24747488 ER PT J AU Milian, MJ Fone, K Steckler, T Horan, WP AF Milian, Mark J. Fone, Kevin Steckler, Thomas Horan, William P. TI Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material DE Prefrontal cortex; Striatum; Motivation; Social cognition; Social interaction; Oxytocin ID TRANSCRANIAL MAGNETIC STIMULATION; CONDITIONED PLACE PREFERENCE; RANDOMIZED CONTROLLED-TRIALS; SOCIAL-INTERACTION DEFICITS; VENTRAL HIPPOCAMPAL LESION; COGNITIVE-BEHAVIOR THERAPY; AUTISM SPECTRUM DISORDERS; 1ST EPISODE PSYCHOSIS; DEVELOPMENTAL NEUROPSYCHIATRIC DISORDERS; NEURODEVELOPMENTAL RAT MODEL AB Schizophrenia is a complex and multifactorial disorder generally diagnosed in young adults at the time of the first psychotic episode of delusions and hallucinations. These positive symptoms can be controlled in most patients by currently-available antipsychotics. Conversely, they are poorly effective against concomitant neurocognitive dysfunction, deficits in social cognition and negative symptoms (NS), which strongly contribute to poor functional outcome. The precise notion of NS has evolved over the past century, with recent studies - underpinned by novel rating methods - suggesting two major sub-domains: "decreased emotional expression", incorporating blunted affect and poverty of speech, and "avolition", which embraces amotivation, asociality and "anhedonia" (inability to anticipate pleasure). Recent studies implicate a dysfunction of frontocortico-temporal networks in the aetiology of NS, together with a disruption of cortico-striatal circuits, though other structures are also involved, like the insular and parietal cortices, amygdala and thalamus. At the cellular level, a disruption of GABAergicglutannatergic balance, dopaminergic signalling and, possibly, oxytocinergic and cannibinoidergic transmission may be involved. Several agents are currently under clinical investigation for the potentially improved control of NS, including oxytocin itself, N-Methyl-D-Aspartate receptor modulators and minocycline. Further, magnetic-electrical "stimulation" strategies to recruit cortical circuits and "cognitive-behavioural-psychosocial" therapies likewise hold promise. To acquire novel insights into the causes and treatment of NS, experimental study is crucial, and opportunities are emerging for improved genetic, pharmacological and developmental modelling, together with more refined readouts related to deficits in reward, sociality and "expression". The present article comprises an integrative overview of the above issues as a platform for this Special Issue of European Neuropsychopharmacology in which five clinical and five preclinical articles treat individual themes in greater detail. This Volume provides, then, a framework for progress in the understanding - and ultimately control - of the debilitating NS of schizophrenia. (c) 2014 Elsevier B.V. and ECNP. C1 [Milian, Mark J.] Inst Rech Servier, F-78290 Paris, France. [Fone, Kevin] Univ Nottingham, Queens Med Ctr, Sch Med, Sch Biomed Sci, Nottingham NG7 2UH, England. [Steckler, Thomas] Janssen Res & Dev, B-2340 Beerse, Belgium. [Horan, William P.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Milian, MJ (reprint author), Inst Rech Servier, 125 Chemin Ronde, F-78290 Paris, France. EM mark.millan@fr.netgrs.com NR 467 TC 10 Z9 11 U1 8 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY PY 2014 VL 24 IS 5 SI SI BP 645 EP 692 DI 10.1016/j.euroneuro.2014.03.008 PG 48 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AI8YE UT WOS:000337212100001 ER PT J AU Malaspina, D Walsh-Messinger, J Gaebel, W Smith, LM Gorun, A Prudent, V Antonius, D Tremeau, F AF Malaspina, Dolores Walsh-Messinger, Julie Gaebel, Wolfgang Smith, Lianne Morris Gorun, Alyson Prudent, Vasthie Antonius, Daniel Tremeau, Fabien TI Negative symptoms, past and present: A historical perspective and moving to DSM-5 SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Diagnosis; Schizophrenia; Emotional expression; Avolition; Negative symptoms; Historical ID SYNDROME SCALE PANSS; 1ST EPISODE PSYCHOSIS; 5 FACTOR MODEL; GENDER-DIFFERENCES; CHRONIC-SCHIZOPHRENIA; SCHIZOAFFECTIVE DISORDER; INTRINSIC MOTIVATION; SOCIAL ANXIETY; RATING-SCALE; FACTORIAL STRUCTURE AB The diagnosis of schizophrenia includes "positive" and "negative" symptoms. These titles were developed to respectively reflect if the symptoms are additions to normal experiences, such as delusions and hallucinations, or if they refer to the absence or the loss of normal emotional function or behavior. This paper describes the history of the negative symptom concept, from its origins up to the considerations for the DSM-5, including the steps that produced the current conceptualizations. The DSM-5 only includes deficits in emotional expression and avolition as negative symptoms, which can be assessed from interview information. Factor analyses show they encompass most other negative symptom items. In addition to using these negative symptoms in a categorical manner to make a diagnosis, the DSM-5 has quantitative severity ratings of the negative symptoms, along with ratings of delusions, cognitive symptoms, motor symptoms, disorganization, depression and mania. With this approach, the different symptom domains, including negative symptoms, can be measured and tracked over time. Another change in the DSM-5 is the dropping of the schizophrenia subtypes that have been included in earlier volumes, as they were not useful in treatment decisions or prognosis. An intended outcome of these changes in DSM-5 is for clinicians to directly treat the individual psychopathological domains of the disorder for optimizing individual outcomes. Finally, this paper includes descriptions of the negative symptom items from over a dozen different scales. (C) 2013 Elsevier B.V. and ECNP. All rights reserved. C1 [Malaspina, Dolores; Walsh-Messinger, Julie; Smith, Lianne Morris; Gorun, Alyson; Prudent, Vasthie; Antonius, Daniel; Tremeau, Fabien] NYU, Sch Med, Dept Psychiat, Inst Social & Psychiat Initiat InSPIRES, New York, NY 10016 USA. [Malaspina, Dolores] NY State Off Mental Hlth, Creedmoor Psychiat Ctr, New York, NY 10003 USA. [Walsh-Messinger, Julie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Gaebel, Wolfgang] Univ Dusseldorf, Fac Med, Dept Psychiat & Psychotherapy, Dusseldorf, Germany. [Prudent, Vasthie] Univ Miami, Miller Sch Med, Jackson Mem Hosp, Dept Psychiat, Miami, FL 33136 USA. [Antonius, Daniel] SUNY Buffalo, Buffalo, NY 14260 USA. [Antonius, Daniel] Erie Cty Forens Mental Hlth Serv, Buffalo, NY 14260 USA. [Tremeau, Fabien] Nathan S Kline Inst Psychiat Res, Dept Psychiat, Orangeburg, NY 10962 USA. RP Malaspina, D (reprint author), NYU, Sch Med, Dept Psychiat, Inst Social & Psychiat Initiat InSPIRES, 1 Pk Ave,8th Floor,Room 222, New York, NY 10016 USA. EM dolores.malaspina@nyumc.org OI Smith, Lianne/0000-0002-6163-4272 FU NIMH [K24 MH01699-11] FX NIMH K24 MH01699-11 (DM) NR 115 TC 12 Z9 12 U1 8 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY PY 2014 VL 24 IS 5 SI SI BP 710 EP 724 DI 10.1016/j.euroneuro.2013.10.018 PG 15 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AI8YE UT WOS:000337212100003 PM 24314851 ER PT J AU Leonard, DA Kurtz, JM Cetrulo, CL AF Leonard, David A. Kurtz, Josef M. Cetrulo, Curtis L., Jr. TI Achieving immune tolerance in hand and face transplantation: a realistic prospect? SO IMMUNOTHERAPY LA English DT Editorial Material DE delayed induction of tolerance; mixed chimerism; translation; transplant tolerance; vascularized composite allotransplantation ID MISMATCHED RENAL-TRANSPLANTATION; MAINTENANCE IMMUNOSUPPRESSION; ALLOGRAFT; INDUCTION; LIVER; RECIPIENTS; CHIMERISM; RESPONSES; KIDNEY; SKIN C1 [Leonard, David A.; Kurtz, Josef M.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Vascularized Composite Allotransplantat Lab, Transplantat Biol Res Ctr,Med Sch, Boston, MA 02115 USA. [Kurtz, Josef M.] Emmanuel Coll, Dept Biol, Boston, MA USA. RP Leonard, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Vascularized Composite Allotransplantat Lab, Transplantat Biol Res Ctr,Med Sch, Boston, MA 02115 USA. EM ccetrulo@mgh.harvard.edu NR 20 TC 6 Z9 6 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X EI 1750-7448 J9 IMMUNOTHERAPY-UK JI Immunotherapy PD MAY PY 2014 VL 6 IS 5 BP 499 EP 502 DI 10.2217/IMT.14.29 PG 4 WC Immunology SC Immunology GA AI9BB UT WOS:000337220000001 PM 24896618 ER PT J AU Morland, LA Mackintosh, MA Greene, CJ Rosen, CS Chard, KM Resick, P Frueh, BC AF Morland, Leslie A. Mackintosh, Margaret-Anne Greene, Carolyn J. Rosen, Craig S. Chard, Kathleen M. Resick, Patricia Frueh, B. Christopher TI Cognitive Processing Therapy for Posttraumatic Stress Disorder Delivered to Rural Veterans via Telemental Health: A Randomized Noninferiority Clinical Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TELEPSYCHIATRY; IRAQ; AFGHANISTAN; TELEHEALTH; VIOLENCE; COMBAT; PTSD; PSYCHOTHERAPY; TELEMEDICINE; POPULATION AB Objective: To compare clinical and process outcomes of cognitive processing therapy-cognitive only version (CPT-C) delivered via videoteleconferencing (VTC) to in-person in a rural, ethnically diverse sample of veterans with posttraumatic stress disorder (PTSD). Method: A randomized clinical trial with a noninferiority design was used to determine if providing CPT-C via VTC is effective and "as good as" in-person delivery. The study took place between March 2009 and June 2013. PTSD was diagnosed per DSM-IV. Participants received 12 sessions of CPT-C via VTC (n = 61) or in-person (n = 64). Assessments were administered at baseline, midtreatment, immediately posttreatment, and 3 and 6 months posttreatment. The primary clinical outcome was posttreatment PTSD severity, as measured by the Clinician-Administered PTSD Scale. Results: Clinical and process outcomes found VTC to be noninferior to in-person treatment. Significant reductions in PTSD symptoms were identified at posttreatment (Cohen d = 0.78, P <.05) and maintained at 3- and 6-month follow-up (d = 0.73, P <.05 and d = 0.76, P <.05, respectively). High levels of therapeutic alliance, treatment compliance, and satisfaction and moderate levels of treatment expectancies were reported, with no differences between groups (for all comparisons, F < 1.9, P >.17). Conclusions: Providing CPT-C to rural residents with PTSD via VTC produced outcomes that were "as good as" in-person treatment. All participants demonstrated significant reductions in PTSD symptoms posttreatment and at follow-up. Results indicate that VTC can offer increased access to specialty mental health care for residents of rural or remote areas. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Morland, Leslie A.; Mackintosh, Margaret-Anne] Dept Vet Affairs Pacific Isl Healthcare Syst, Natl Ctr PTSD, Pacific Islands Div, Honolulu, HI 96819 USA. [Morland, Leslie A.] Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. [Greene, Carolyn J.; Rosen, Craig S.] Dept Vet Affairs Palo Alto Healthcare Syst, Disseminat & Training Div, Natl Ctr PTSD, Palo Alto, CA USA. [Rosen, Craig S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Chard, Kathleen M.] Univ Cincinnati, Coll Med, Cincinnati VA Med Ctr, Trauma Recovery Ctr, Cincinnati, OH USA. [Chard, Kathleen M.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Resick, Patricia] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Resick, Patricia] Boston Univ, Boston, MA 02215 USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Frueh, B. Christopher] Baylor Coll Med, Houston, TX 77030 USA. RP Morland, LA (reprint author), Dept Vet Affairs Pacific Isl Healthcare Syst, Natl Ctr PTSD, Pacific Islands Div, 3375 Koapaka St, Honolulu, HI 96819 USA. EM leslie.morland@va.gov OI Mackintosh, Margaret-Anne/0000-0002-2725-3177 FU Department of Defense [PT074516]; Office of Research and Development, Health Services R&D Service grant, Department of Veterans Affairs [DHI-07-259] FX This research was supported by grant PT074516 from the Department of Defense. This material is also based on work supported in part by the Office of Research and Development, Health Services R&D Service grant DHI-07-259, Department of Veterans Affairs. NR 45 TC 24 Z9 24 U1 5 U2 29 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2014 VL 75 IS 5 BP 470 EP 476 DI 10.4088/JCP.13m08842 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI9LZ UT WOS:000337255400010 PM 24922484 ER PT J AU Beach, SR Kostis, WJ Celano, CM Januzzi, JL Ruskin, JN Noseworthy, PA Huffman, JC AF Beach, Scott R. Kostis, William J. Celano, Christopher M. Januzzi, James L. Ruskin, Jeremy N. Noseworthy, Peter A. Huffman, Jeff C. TI Meta-Analysis of Selective Serotonin Reuptake Inhibitor-Associated QTc Prolongation SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TORSADE-DE-POINTES; INTERVAL PROLONGATION; ANTIDEPRESSANT DRUGS; DEPRESSED-PATIENTS; MAJOR DEPRESSION; HEART-DISEASE; TRICYCLIC ANTIDEPRESSANTS; RANDOMIZED EVALUATION; PSYCHOTROPIC-DRUGS AB Objective: To evaluate the association between selective serotonin reuptake inhibitors (SSRIs) and corrected QT interval (QTc) prolongation via meta-analysis of prospective studies. Data Sources: PubMed/MEDLINE database (January 1, 1975-August 15, 2012), with additional reports identified using hand searches of reference lists of relevant articles. Key words searched were QT, torsades de pointes, and sudden cardiac death, combined with antidepressants, citalopram, escitalopram, fluoxetine, sertraline, paroxetine, and fluvoxamine. English-, Spanish-, and German-language articles were included. Study Selection: Two reviewers independently identified prospective controlled studies in adults that reported data related to QTc intervals prior to and following treatment with SSRIs. Data Extraction and Synthesis: Three reviewers independently extracted study-level data including population characteristics, method of QTc measurement and treatment and outcome data. Two independent reviewers critiqued study quality. Publication bias was assessed visually using a funnel plot and quantitatively. Heterogeneity was measured using Cochran Q statistic. Results: Sixteen articles (with 25 distinct data subsets) involving 4,292 patients were included. SSRIs were associated with a dose-dependent increase in QTc interval compared to placebo (+ 6.10 milliseconds; 95% CI, 3.47-8.73; P <.001). Tricyclic antidepressants (TCAs) were associated with a significantly greater QTc increase than SSRIs (TCA prolongation, 7.05 milliseconds; 95% CI, 3.84-10.27 greater than SSRIs; P <.001). With respect to specific SSRI agents, citalopram was associated with significantly greater QTc prolongation than sertraline, paroxetine, and fluvoxamine. Conclusions: SSRIs were associated with a modest but statistically significant increase in the QTc interval, although to a lesser extent than TCAs; this finding was not limited to any single study. Citalopram was associated with more QTc prolongation than most other SSRIs. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Beach, Scott R.; Kostis, William J.; Celano, Christopher M.; Januzzi, James L.; Ruskin, Jeremy N.; Noseworthy, Peter A.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Beach, Scott R.; Celano, Christopher M.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kostis, William J.; Januzzi, James L.; Ruskin, Jeremy N.; Noseworthy, Peter A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Beach, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Warren 605, Boston, MA 02114 USA. EM sbeach1@partners.org NR 56 TC 34 Z9 34 U1 3 U2 21 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2014 VL 75 IS 5 BP E441 EP E449 DI 10.4088/JCP.13r08672 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI9LZ UT WOS:000337255400005 PM 24922496 ER PT J AU Harte, CB AF Harte, Christopher B. TI Concurrent Relations among Cigarette Smoking Status, Resting Heart Rate Variability, and Erectile Response SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Smoking; Nicotine; Heart Rate Variability; Cardiac Autonomic Function; Sexual Arousal; Erectile Tumescence; Erectile Physiology ID PENILE-VAGINAL INTERCOURSE; POWER SPECTRAL-ANALYSIS; BLOOD-PRESSURE; ENDOTHELIAL FUNCTION; INTERNATIONAL INDEX; NERVOUS-SYSTEM; DYSFUNCTION; MEN; NICOTINE; CESSATION AB IntroductionHeart rate variability (HRV) is a marker of sympathovagal balance; it has been implicated in erectile function and is also altered by tobacco use. Furthermore, smoking and erectile health are strongly related, given that smokers are at increased risk for erectile dysfunction. Few studies have explored the interrelationships between smoking, HRV, and erectile function concurrently. AimThe aim of this study was to examine potential mechanisms underlying tobacco's effects on penile hemodynamics by exploring the mediating role of HRV. MethodsThe sample comprised 119 men (smokers=64; nonsmokers=55) (mean age 28.90 years; standard deviation (SD) 11.68; range 18-58) selected from the control conditions of three previously published experiments. Participants were free from a history of cardiovascular disease, myocardial infarct, and/or cardiac/cardiovascular medication use. During a laboratory visit, self-report, anthropometric, cardiovascular, and electrocardiographic data were assessed, as well as sexual arousal responses elicited from viewing an erotic film. Main Outcome MeasuresObjective sexual arousal indices (circumferential change via penile plethysmography), self-reported erectile function (per the erectile function domain score of the International Index of Erectile Function [IIEF-EF]), and time- (SD of beat-to-beat intervals) and frequency-domain parameters of HRV (ratio of low-frequency [LF] power to high-frequency [HF] power [LF/HF ratio]) were assessed. ResultsBeing a current long-term cigarette smoker was associated with dysregulated sympathovagal balance (higher LF/HF ratios, indicative of sympathetic nervous system dominance), which in turn showed inverse relations with magnitude of erectile tumescence. HRV did not mediate relations between tobacco use and either IIEF-EF scores or resting penile circumference. ConclusionsFindings suggest that dysfunctional cardiac autonomic tone may be an underlying mechanism by which tobacco exerts its deleterious effects on erectile health. Further research is necessary to determine whether this relationship is mechanistic in nature, or whether it is better explained by other health factors. Harte CB. Concurrent relations among cigarette smoking status, resting heart rate variability, and erectile response. J Sex Med 2014;11:1230-1239. C1 [Harte, Christopher B.] Boston Univ, Sch Med, Dept Psychiat, Res Serv,VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Harte, CB (reprint author), VA Boston Healthcare Syst, Res Serv, 150 S Huntington Ave,116-B4, Boston, MA 02130 USA. EM christopher.harte@va.gov OI Harte, Christopher/0000-0002-8097-7369 NR 62 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2014 VL 11 IS 5 BP 1230 EP 1239 DI 10.1111/jsm.12486 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AI9WG UT WOS:000337293700014 PM 24576257 ER PT J AU Sorvillo, N Kaijen, PH Matsumoto, M Fujimura, Y van der Zwaan, C Verbij, FC Pos, W Fijnheer, R Voorberg, J Meijer, AB AF Sorvillo, N. Kaijen, P. H. Matsumoto, M. Fujimura, Y. van der Zwaan, C. Verbij, F. C. Pos, W. Fijnheer, R. Voorberg, J. Meijer, A. B. TI Identification of N-linked glycosylation and putative O-fucosylation, C-mannosylation sites in plasma derived ADAMTS13 SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ADAMTS-13 protein human; autoimmune diseases; glycosylation; mass spectrometry; thrombotic thrombocytopenic purpura ID THROMBOTIC THROMBOCYTOPENIC PURPURA; VON-WILLEBRAND-FACTOR; THROMBOSPONDIN TYPE-1 REPEATS; MASS-SPECTROMETRY; DENDRITIC CELLS; SECRETION; GLYCANS; DISSOCIATION; PEPTIDES AB BackgroundAcquired deficiency of ADAMTS13 causes a rare and life-threatening disorder called thrombotic thrombocytopenic purpura (TTP). Several studies have shown that aberrant glycosylation can play an important role in the pathogenesis of autoimmune diseases. N-linked glycosylation and putative O-fucosylation sites have been predicted or identified in recombinant ADAMTS13. However, it is not known which of these sites are glycosylated in plasma derived ADAMTS13. ObjectivesHere we investigated the presence of putative O-fucosylation, C-mannosylation and N-linked glycosylation sites on plasma derived ADAMTS13. Methods/ResultsSites of N-linked glycosylation were determined by the use of peptide N-glycosidase-F (PNGase F), which removes the entire carbohydrate from the side chain of asparagines. Nine of the 10 predicted N-linked glycosylation sites were identified in or near the metalloproteinase, spacer, thrombospondin type 1 repeat (TSR1) and the CUB domain of plasma ADAMTS13. Moreover, six putative O-fucosylated sites were identified in the TSR domains of plasma ADAMTS13 by performing searches of the tandem mass spectrometry (MS/MS) data for loss of hexose (162Da), deoxyhexose (146Da), or hexose-deoxyhexose (308Da). The use of electron transfer dissociation (ETD) allowed for unambiguous identification of the modified sites. In addition to putative O-fucosylation and N-linked glycosylation, two putative C-mannosylation sites were identified within the TSR1 and TSR4 domains of ADAMTS13. ConclusionsOur data identify several glycosylation sites on plasma derived ADAMTS13. We anticipate that our findings may be relevant for the initiation of autoimmune reactivity against ADAMTS13 in patients with acquired TTP. C1 [Sorvillo, N.; Kaijen, P. H.; van der Zwaan, C.; Verbij, F. C.; Pos, W.; Voorberg, J.; Meijer, A. B.] Sanquin AMC Landsteiner Lab, Dept Plasma Prot, Amsterdam, Netherlands. [Matsumoto, M.; Fujimura, Y.] Nara Med Univ, Dept Blood Transfus Med, Kashihara, Nara 634, Japan. [Pos, W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Fijnheer, R.] Univ Med Ctr Utrecht, Dept Haematol, Utrecht, Netherlands. [Voorberg, J.] Univ Amsterdam, Dept Vasc Med, Amsterdam, Netherlands. [Meijer, A. B.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands. RP Voorberg, J (reprint author), Acad Med Ctr, Dept Plasma Prot, Sanquin Res & Landsteiner Lab, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. EM j.voorberg@sanquin.nl FU Takeda Medical Foundation; [PPOC-08-021] FX This study was supported by grant PPOC-08-021. Grant support from Takeda Medical Foundation is gratefully acknowledged. NR 30 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD MAY PY 2014 VL 12 IS 5 BP 670 EP 679 DI 10.1111/jth.12535 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AI9XE UT WOS:000337298100013 PM 24977290 ER PT J AU Liu, Q Wu, D Ni, N Ren, HX Luo, CM He, CW Kang, JX Wan, JB Su, HX AF Liu, Qiang Wu, Di Ni, Na Ren, Huixia Luo, Chuanming He, Chengwei Kang, Jing-Xuan Wan, Jian-Bo Su, Huanxing TI Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury SO MARINE DRUGS LA English DT Article DE oxidative stress; DHA; fat-1; neural progenitor cells ID DOCOSAHEXAENOIC ACID; NRF2-ARE PATHWAY; TRANSGENIC MICE; MOUSE MODEL; FAT-1 MICE; STRESS; RATS; PERFORMANCE; ASTROCYTES; IMPROVES AB The omega-3 polyunsaturated fatty acids (omega-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of omega-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against H2O2-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert omega-6 to omega-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H2O2 as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that omega-3 PUFAs resist oxidative injury to NPCs. C1 [Liu, Qiang; Wu, Di; Ni, Na; Ren, Huixia; Luo, Chuanming; He, Chengwei; Wan, Jian-Bo; Su, Huanxing] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macao 999078, Peoples R China. [Kang, Jing-Xuan] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing-Xuan] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Su, HX (reprint author), Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macao 999078, Peoples R China. EM yb37525@umac.mo; mb35801@umac.mo; mb15844@umac.mo; yb27526@umac.mo; 15989166366@163.com; chengweihe@umac.mo; jxkang@mgh.harvard.edu; jbwan@umac.mo; huanxingsu@umac.mo OI Wan, Jian-Bo/0000-0002-6750-2617 FU Macao Science and Technology Development Fund [003/2012/A, 018/2013/A1]; university of Macau [MYRG122 (Y1-L3)-ICMS12-SHX, MYRG110 (Y1-L2)-ICMS13-SHX] FX This study was supported by Macao Science and Technology Development Fund (003/2012/A and 018/2013/A1) and multi-year research grant, university of Macau, MYRG122 (Y1-L3)-ICMS12-SHX and MYRG110 (Y1-L2)-ICMS13-SHX. NR 35 TC 11 Z9 11 U1 2 U2 22 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD MAY PY 2014 VL 12 IS 5 BP 2341 EP 2356 DI 10.3390/md12052341 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AI8JU UT WOS:000337160500001 PM 24786451 ER PT J AU Chang, YP Chu, YH AF Chang, Yi-Pin Chu, Yen-Ho TI Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on alpha(1)-Antitrypsin Deficiency SO MOLECULES LA English DT Review DE antitrypsin; alanine scanning; conformational disease; iterative deconvolution; peptide library; positional scanning; split-and-mix; surface plasmon resonance; truncation library; urea gel ID INSOLUBLE POLYMER SUPPORTS; SURFACE-PLASMON RESONANCE; BETA-SHEET-A; SERPIN POLYMERIZATION; ALPHA1-ANTITRYPSIN DEFICIENCY; CHEMICAL SYNTHESIS; CRYSTAL-STRUCTURE; REACTIVE-CENTER; GENERAL-METHOD; LARGE NUMBERS AB The design, synthesis and screening of diversity-oriented peptide libraries using a "libraries from libraries" strategy for the development of inhibitors of alpha(1)-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods. C1 [Chang, Yi-Pin] Forsyth Inst, Cambridge, MA 02142 USA. [Chu, Yen-Ho] Natl Chung Cheng Univ, Dept Chem & Biochem, Chiayi 62102, Taiwan. RP Chu, YH (reprint author), Natl Chung Cheng Univ, Dept Chem & Biochem, 168 Univ Rd, Chiayi 62102, Taiwan. EM cheyhc@ccu.edu.tw FU National Science Council of Taiwan, ROC [NSC100-2113-M-194-003-MY3, NSC97-2113-M-194-006-MY3]; National Chung Cheng University [CCU101-00885-01] FX We thank Chien-Hung Chen and Kai-Chun Lin from laboratories of Wun-Shaing Wayne Chang (National Health Research Institutes, Taiwan) for their assistance in protein purification. We also thank for the artwork of Ms. Lucie Drdova in Figure 2. We are particularly grateful to Ravi Mahadeva (University of Cambridge, UK) and Wun-Shaing Wayne Chang (National Health Research Institutes, Taiwan) for helpful discussions throughout the course of the study. This work was supported by grants from the National Science Council of Taiwan, ROC (NSC100-2113-M-194-003-MY3 and NSC97-2113-M-194-006-MY3) and an excellent research award from National Chung Cheng University (CCU101-00885-01). NR 63 TC 1 Z9 1 U1 3 U2 13 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD MAY PY 2014 VL 19 IS 5 BP 6330 EP 6348 DI 10.3390/molecules19056330 PG 19 WC Chemistry, Organic SC Chemistry GA AI7WR UT WOS:000337113000054 PM 24840902 ER PT J AU Santiago, GF Susarla, SM Al Rakan, M Coon, D Rada, EM Sarhane, KA Shores, JT Bonawitz, SC Cooney, D Sacks, J Murphy, RJ Fishman, EK Brandacher, G Lee, WPA Liacouras, P Grant, G Armand, M Gordon, CR AF Santiago, Gabriel F. Susarla, Srinivas M. Al Rakan, Mohammed Coon, Devin Rada, Erin M. Sarhane, Karim A. Shores, Jamie T. Bonawitz, Steven C. Cooney, Damon Sacks, Justin Murphy, Ryan J. Fishman, Elliot K. Brandacher, Gerald Lee, W. P. Andrew Liacouras, Peter Grant, Gerald Armand, Mehran Gordon, Chad R. TI Establishing Cephalometric Landmarks for the Translational Study of Le Fort-Based Facial Transplantation in Swine: Enhanced Applications Using Computer-Assisted Surgery and Custom Cutting Guides SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TOTAL FACE; DOUBLE JAW; DISTRACTION OSTEOGENESIS; SURGICAL EXPERIMENTATION; QUANTITATIVE ASSESSMENT; MODEL; MORPHOLOGY; SIMULATION AB Background: Le Fort-based, maxillofacial allotransplantation is a reconstructive alternative gaining clinical acceptance. However, the vast majority of single-jaw transplant recipients demonstrate less-than-ideal skeletal and dental relationships, with suboptimal aesthetic harmony. The purpose of this study was to investigate reproducible cephalometric landmarks in a large-animal model, where refinement of computer-assisted planning, intraoperative navigational guidance, translational bone osteotomies, and comparative surgical techniques could be performed. Methods: Cephalometric landmarks that could be translated into the human craniomaxillofacial skeleton, and that would remain reliable following maxillofacial osteotomies with midfacial alloflap inset, were sought on six miniature swine. Le Fort I- and Le Fort III-based alloflaps were harvested in swine with osteotomies, and all alloflaps were either autoreplanted or transplanted. Cephalometric analyses were performed on lateral cephalograms preoperatively and postoperatively. Critical cephalometric data sets were identified with the assistance of surgical planning and virtual prediction software and evaluated for reliability and translational predictability. Results: Several pertinent landmarks and human analogues were identified, including pronasale, zygion, parietale, gonion, gnathion, lower incisor base, and alveolare. Parietale-pronasale-alveolare and parietale-pronasale-lower incisor base were found to be reliable correlates of sellion-nasion-A point angle and sellion-nasion-B point angle measurements in humans, respectively. Conclusions: There is a set of reliable cephalometric landmarks and measurement angles pertinent for use within a translational large-animal model. These craniomaxillofacial landmarks will enable development of novel navigational software technology, improve cutting guide designs, and facilitate exploration of new avenues for investigation and collaboration. C1 Johns Hopkins Univ, Dept Plast & Reconstruct Surg, Sch Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Radiol, Sch Med, Baltimore, MD 21287 USA. Walter Reed Natl Mil Med Ctr, Dept Otolaryngol Head & Neck Surg, Bethesda, MD USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Johns Hopkins Appl Phys Lab, Res & Engn Dev Dept, Robot & Auton Grp, Baltimore, MD USA. Naval Postgrad Dent Sch, Med Applicat Ctr 3D, Dept Radiol, Walter Reed Natl Mil Med Ctr, Monterey, CA USA. RP Gordon, CR (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, 601 North Caroline St, Baltimore, MD 21287 USA. EM cgordon@jhmi.edu RI Brandacher, Gerald/L-7540-2016; OI fishman, elliot/0000-0002-2567-1658; Susarla, Srinivas/0000-0003-0155-8260 FU American Society of Maxillofacial Surgeons (American Society of Maxillofacial Surgeons Basic Science Research grant); American Association of Plastic Surgeons (Furnas Academic Scholar Award); Accelerated Translational Investigational Program at Johns Hopkins - (National Institutes of Health); National Center for Advancing Translational Sciences, a component of the National Institutes of Health; National Institutes of Health Roadmap for Medical Research; National Center for Advancing Translational Sciences [UL1TR000424-06]; National Institutes of Health (National Center for Advancing Translational Sciences) [UL1TR000424-06] FX Outside funding from various grants was used for a portion of this study. This includes grant support by the American Society of Maxillofacial Surgeons (2011 American Society of Maxillofacial Surgeons Basic Science Research grant), the American Association of Plastic Surgeons (2012-14 Furnas Academic Scholar Award), and the Accelerated Translational Investigational Program at Johns Hopkins (funded by the National Institutes of Health).; This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research, which is funded in part by the National Center for Advancing Translational Sciences, a component of the National Institutes of Health, and National Institutes of Health Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins Institute for Clinical and Translational Research, the National Center for Advancing Translational Sciences, or the National Institutes of Health (National Center for Advancing Translational Sciences grant UL1TR000424-06). NR 18 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2014 VL 133 IS 5 BP 1138 EP 1151 DI 10.1097/PRS.0000000000000110 PG 14 WC Surgery SC Surgery GA AI9XR UT WOS:000337300900047 PM 24445879 ER PT J AU Linnemann, AK Baan, M Davis, DB AF Linnemann, Amelia K. Baan, Mieke Davis, Dawn Belt TI Pancreatic beta-Cell Proliferation in Obesity SO ADVANCES IN NUTRITION LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; HIGH-FAT DIET; GLUCAGON-LIKE PEPTIDE-1; DIABETES SUSCEPTIBILITY LOCI; SCALE ASSOCIATION ANALYSIS; INDUCED INSULIN-RESISTANCE; ACTIVATED-RECEPTOR-GAMMA; CYCLIN D2 EXPRESSION; GENE-EXPRESSION; GLUCOSE-INTOLERANCE AB Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic beta-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in beta-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to beta-cell proliferation. This review focuses on the mechanisms regulating obesity-induced beta-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven beta-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of beta-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study. C1 [Linnemann, Amelia K.; Baan, Mieke; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53706 USA. [Baan, Mieke] Univ Wisconsin, Sch Vet Med, Madison, WI USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Davis, DB (reprint author), Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53706 USA. EM dbd@medicine.wisc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK083442]; NIH Ruth L. Kirschstein National Research Service Award Institutional Training Grant from the National Center for Research Resources [T32 RR023916/OD010423] FX D.B.D. is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK083442 M.B. is supported by the NIH Ruth L. Kirschstein National Research Service Award Institutional Training Grant T32 RR023916/OD010423 from the National Center for Research Resources. The William S. Middleton Memorial Veterans Hospital provided resources and use of facilities. The contents of this manuscript do not necessarily represent the views of the Department of Veterans Affairs or the U.S. Government NR 95 TC 16 Z9 16 U1 0 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 EI 2156-5376 J9 ADV NUTR JI Adv. Nutr. PD MAY PY 2014 VL 5 IS 3 BP 278 EP 288 DI 10.3945/an.113.005488 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AI5CV UT WOS:000336883900007 PM 24829474 ER PT J AU Kristensen, JM Treebak, JT Schjerling, P Goodyear, L Wojtaszewski, JFP AF Kristensen, Jonas Moller Treebak, Jonas T. Schjerling, Peter Goodyear, Laurie Wojtaszewski, Jorgen F. P. TI Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE metformin; AMPK; skeletal muscle; glucose uptake; insulin ID ACTIVATED PROTEIN-KINASE; RAT SKELETAL-MUSCLE; GLUT4 TRANSLOCATION; DIABETES-MELLITUS; RESPIRATORY-CHAIN; ZUCKER RATS; FIBER-TYPE; IN-VITRO; INCREASES; EXERCISE AB Metformin-induced activation of the 5'-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPK alpha(2) mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (similar to 45%, P < 0.01) but not of AMPK KD mice. Insulin signaling at the level of Akt protein expression or Thr(308) and Ser(473) phosphorylation was not changed by metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr(308)/Ser(473) and TBC1D4 Thr(642)/Ser(711) phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment. C1 [Kristensen, Jonas Moller; Treebak, Jonas T.; Wojtaszewski, Jorgen F. P.] Univ Copenhagen, Mol Physiol Grp, August Krogh Ctr, Dept Nutr Exercise & Sport Sci, DK-2100 Copenhagen O, Denmark. [Schjerling, Peter] Univ Copenhagen, Bispebjerg Hosp, Dept Orthoped Surg M, Inst Sports Med, DK-2100 Copenhagen O, Denmark. [Schjerling, Peter] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Hlth Aging, DK-2100 Copenhagen O, Denmark. [Goodyear, Laurie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Goodyear, Laurie] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wojtaszewski, JFP (reprint author), Univ Copenhagen, Mol Physiol Grp, August Krogh Ctr, Dept Nutr Exercise & Sport Sci, Univ Pk 13, DK-2100 Copenhagen O, Denmark. EM jwojtaszewski@nexs.ku.dk RI Wojtaszewski, Jorgen /P-6583-2014; Treebak, Jonas/B-4521-2017; OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Treebak, Jonas/0000-0003-1488-7012; Schjerling, Peter/0000-0001-7138-3211 FU Danish Medical Research Council; Novo Nordisk Foundation; Danish Diabetes Association; Nordea Foundation; Lundbeck Foundation; Danish Ministry of Science, Technology and Innovation; Danish Agency for Science, Technology and Innovation, Denmark FX The study was supported by grants from the Danish Medical Research Council, The Novo Nordisk Foundation, the Danish Diabetes Association, Nordea Foundation and the Lundbeck Foundation. This work is part of the research program of the UNIK: Food, Fitness & Pharma for Health and Disease (see http://www.foodfitnesspharma.ku.dk/). The UNIK project is supported by the Danish Ministry of Science, Technology and Innovation. J. T. Treebak was supported by a postdoctoral fellowship from The Danish Agency for Science, Technology and Innovation, Denmark. NR 76 TC 14 Z9 14 U1 0 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 2014 VL 306 IS 10 BP E1099 EP E1109 DI 10.1152/ajpendo.00417.2013 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA AI5KV UT WOS:000336906300001 PM 24644243 ER PT J AU Chacon-Heszele, MF Zuo, XF Hellman, NE McKenna, S Choi, SY Huang, LW Tobias, JW Park, KM Lipschutz, JH AF Chacon-Heszele, Maria F. Zuo, Xiaofeng Hellman, Nathan E. McKenna, Sarah Choi, Soo Young Huang, Liwei Tobias, John W. Park, Kwon Moo Lipschutz, Joshua H. TI Novel MAPK-dependent and -independent tubulogenes identified via microarray analysis of 3D-cultured Madin-Darby canine kidney cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE mitogen-activated protein kinase; matrix metalloproteinase; development; kidney; tubulogenesis ID HEPATOCYTE GROWTH-FACTOR; IN-VITRO; EPITHELIAL-CELLS; MDCK CELLS; LINE MDCK; ENDOPLASMIC-RETICULUM; EMBRYONIC KIDNEY; GAMMA-CATENIN; MORPHOGENESIS; EXPRESSION AB Cystogenesis and tubulogenesis are basic building blocks for many epithelial organs, including the kidney. Most researchers have used two-dimensional (2D) cell culture to investigate signaling pathways downstream of hepatocyte growth factor (HGF). We hypothesize that three-dimensional (3D) collagen-grown Madin-Darby canine kidney (MDCK) cells, which form cysts and then tubulate in response to HGF, are a much more in vivo-like system for the identification of novel tubulogenes. With the use of a canine microarray containing over 20,000 genes, 2,417 genes were identified as potential tubulogenes that were differentially regulated, exclusively in 3D-grown MDCK cells. Among these, 840 were dependent on MAPK signaling. Importantly, this work shows that many putative tubulogenes, previously identified via microarray analysis of 2D cultures, including by us, do not change in 3D culture and vice versa. The use of a 3D-culture system allowed for the identification of novel MAPK dependent and -independent genes that regulate early renal tubulogenesis in vitro, e. g., matrix metalloproteinase 1 (MMP1). Knockdown of MMP1 led to defects in cystogenesis and tubulogenesis in 3D-grown MDCK cells, most likely due to problems establishing normal polarity. We suggest that data obtained from 2D cultures, even those using MDCK cells treated with HGF, should not be automatically extrapolated to factors important for cystogenesis and tubulogenesis. Instead, 3D culture, which more closely replicates the biological environment and is therefore a more accurate model for identifying tubulogenes, is preferred. Results from the present analysis will be used to build a more accurate model of the signaling pathways that control cystogenesis and tubulogenesis. C1 [Chacon-Heszele, Maria F.; Zuo, Xiaofeng; Hellman, Nathan E.; McKenna, Sarah; Choi, Soo Young; Huang, Liwei; Lipschutz, Joshua H.] Univ Penn, Renal Electrolyte & Hypertens Div, Dept Med, Philadelphia, PA 19104 USA. [Tobias, John W.] Univ Penn, Genom Inst, Bioinformat Core, Philadelphia, PA 19104 USA. [Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 702701, South Korea. [Lipschutz, Joshua H.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Lipschutz, JH (reprint author), Univ Penn, Renal Electrolyte & Hypertens Div, Rm 405C,Clin Res Bldg, Philadelphia, PA 19104 USA. EM jhlipsch@mail.med.upenn.edu FU VA Merit Award [I01BX000820]; National Institute of Diabetes and Digestive and Kidney Diseases [DK069909, DK047757, DK093625]; NephHope Foundation; Satellite Healthcare (Norman S. Coplon Extramural Research Grant); University of Pennsylvania Translational Medicine Institute (Pilot Grant) FX Support for this work was provided, in part, by grants from the VA Merit Award (I01BX000820 to J. H. Lipschutz), National Institute of Diabetes and Digestive and Kidney Diseases (DK069909 and DK047757 to J. H. Lipschutz and DK093625 to L. Huang), NephHope Foundation (fellowship to M. F. Chacon-Heszele), Satellite Healthcare (Norman S. Coplon Extramural Research Grant to J. H. Lipschutz), and University of Pennsylvania Translational Medicine Institute (Pilot Grant to J. H. Lipschutz). NR 46 TC 4 Z9 4 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2014 VL 306 IS 9 BP F1047 EP F1058 DI 10.1152/ajprenal.00589.2013 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AI4OO UT WOS:000336844900011 PM 24573390 ER PT J AU Kemp, JJ Lickel, JJ Deacon, BJ AF Kemp, Joshua J. Lickel, James J. Deacon, Brett J. TI Effects of a chemical imbalance causal explanation on individuals' perceptions of their depressive symptoms SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Depression; Chemical imbalance; Stigma; Prognosis; Etiology ID MENTAL-DISORDER; MOOD-REGULATION; STIGMA; EXPECTANCIES AB Although the chemical imbalance theory is the dominant causal explanation of depression in the United States, little is known about the effects of this explanation on depressed individuals. This experiment examined the impact of chemical imbalance test feedback on perceptions of stigma, prognosis, negative mood regulation expectancies, and treatment credibility and expectancy. Participants endorsing a past or current depressive episode received results of a bogus but credible biological test demonstrating their depressive symptoms to be caused, or not caused, by a chemical imbalance in the brain. Results showed that chemical imbalance test feedback failed to reduce self-blame, elicited worse prognostic pessimism and negative mood regulation expectancies, and led participants to view pharmacotherapy as more credible and effective than psychotherapy. The present findings add to a growing literature highlighting the unhelpful and potentially iatrogenic effects of attributing depressive symptoms to a chemical imbalance. Clinical and societal implications of these findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kemp, Joshua J.; Deacon, Brett J.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Lickel, James J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Deacon, BJ (reprint author), Univ Wyoming, Dept Psychol, Dept 3415,1000 E Univ Ave, Laramie, WY 82071 USA. EM bdeacon@uwyo.edu NR 30 TC 8 Z9 8 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD MAY PY 2014 VL 56 BP 47 EP 52 DI 10.1016/j.brat.2014.02.009 PG 6 WC Psychology, Clinical SC Psychology GA AI6WJ UT WOS:000337017400007 PM 24657311 ER PT J AU Januzzi, JL Hauptman, PJ AF Januzzi, James L., Jr. Hauptman, Paul J. TI Reversed Reverse Remodeling Can Biomonitoring Solve the Clinical Conundrum of the 3Rs? SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE Editorials; drug therapy; heart failure ID CHRONIC HEART-FAILURE; PROGNOSTIC VALUE; THERAPY; ASSOCIATION; CARDIOLOGY; PROTECT; ST2 C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hauptman, Paul J.] St Louis Univ, Div Cardiol, Dept Med, Sch Med, St Louis, MO 63103 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 18 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2014 VL 7 IS 3 BP 388 EP 390 DI 10.1161/CIRCHEARTFAILURE.114.001357 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3WV UT WOS:000336796900002 PM 24847126 ER PT J AU Mentz, RJ Greene, SJ Ambrosy, AP Vaduganathan, M Subacius, HP Swedberg, K Maggioni, AP Nodari, S Ponikowski, P Anker, SD Butler, J Gheorghiade, M AF Mentz, Robert J. Greene, Stephen J. Ambrosy, Andrew P. Vaduganathan, Muthiah Subacius, Haris P. Swedberg, Karl Maggioni, Aldo P. Nodari, Savina Ponikowski, Piotr Anker, Stefan D. Butler, Javed Gheorghiade, Mihai TI Clinical Profile and Prognostic Value of Anemia at the Time of Admission and Discharge Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction Findings From the EVEREST Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE anemia; heart failure; hemoglobin; hospitalization ID DARBEPOETIN-ALPHA; RENAL-FUNCTION; DOUBLE-BLIND; HEMOGLOBIN CONCENTRATION; VASOPRESSIN ANTAGONISM; TOLVAPTAN EVEREST; PREVALENCE; MORTALITY; EFFICACY; OUTCOMES AB Background-Anemia has been associated with worse outcomes in patients with chronic heart failure (HF). We aimed to characterize the clinical profile and postdischarge outcomes of hospitalized HF patients with anemia at admission or discharge. Methods and Results-An analysis was performed on 3731 (90%) of 4133 hospitalized HF patients with ejection fraction <= 40% enrolled in the Efficacy of Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial with baseline hemoglobin data, comparing the clinical characteristics and outcomes (all-cause mortality and cardiovascular mortality or HF hospitalization) of patients with and without anemia (hemoglobin <12 g/dL for women and <13 g/dL for men) on admission or discharge/day 7. Overall, 1277 patients (34%) were anemic at baseline, which persisted through discharge in 73% and resolved in 27%; 6% of patients without baseline anemia developed anemia by discharge or day 7. Patients with anemia were older, with lower blood pressure, and higher creatinine and natriuretic peptide levels compared with those without anemia (all P<0.05). After risk adjustment, anemia at discharge, but not admission, was independently associated with increased all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.05-1.60; P=0.015; and hazard ratio, 0.94; 95% confidence interval, 0.76-1.15; P=0.53, respectively) and cardiovascular mortality plus HF hospitalization early postdischarge (<= 100 days; hazard ratio 1.73; 95% confidence interval, 1.37-2.18; P<0.001; and hazard ratio, 0.92; 95% confidence interval, 0.73-1.16; P=0.47, respectively). Neither baseline nor discharge anemia was associated with long-term cardiovascular mortality plus HF hospitalization (>100 days) on adjusted analysis (both P>0.1). Conclusions-Among hospitalized HF patients with reduced ejection fraction, modest anemia at discharge but not baseline was associated with increased all-cause mortality and short-term cardiovascular mortality plus HF hospitalization. C1 [Mentz, Robert J.] Duke Univ, Med Ctr, Durham, NC USA. [Greene, Stephen J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Subacius, Haris P.; Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Maggioni, Aldo P.] Assoc Nazl Med Cardiol Osped Res Ctr, Florence, Italy. [Nodari, Savina; Ponikowski, Piotr] Univ Brescia, Brescia, Italy. [Nodari, Savina; Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. [Anker, Stefan D.] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 E Huron St,Galter 3-150, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka, Inc (Rockville, MD); National Institute of General Medical Sciences [T32GM086330]; Center for Cardiovascular Innovation, Northwestern University FX Financial and material support for Efficacy of Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST) was provided by Otsuka, Inc (Rockville, MD). Database management was performed by the sponsor. H. P. Subacius conducted all analyses for this report with funding from the Center for Cardiovascular Innovation, Northwestern University. Dr Mentz is supported by the National Institute of General Medical Sciences (T32GM086330). The authors are solely responsible for the design and conduct of this study, drafting, and editing of the article and its final contents. NR 30 TC 9 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2014 VL 7 IS 3 BP 401 EP U42 DI 10.1161/CIRCHEARTFAILURE.113.000840 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3WV UT WOS:000336796900005 PM 24737459 ER PT J AU Yoon, WJ Daglilar, ES Fernandez-del Castillo, C Mino-Kenudson, M Pitman, MB Brugge, WR AF Yoon, Won Jae Daglilar, Ebubekir S. Fernandez-del Castillo, Carlos Mino-Kenudson, Mari Pitman, Martha B. Brugge, William R. TI Peritoneal seeding in intraductal papillary mucinous neoplasm of the pancreas patients who underwent endoscopic ultrasound-guided fine-needle aspiration: The PIPE Study SO ENDOSCOPY LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; CYSTIC NEOPLASMS; CARCINOMATOSIS; MANAGEMENT; TUMOR; FNA; CANCER; RECURRENCE; DIAGNOSIS; RESECTION AB Background and study aims: There have been concerns about peritoneal seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mucinous pancreatic cystic lesions. The aims of this study were to determine the frequency of postoperative peritoneal seeding in patients with intraductal papillary mucinous neoplasm (IPMN) who had undergone pre-operative EUS-FNA and to compare it with that of patients with IPMN who had surgery with no pre-operative tissue sampling. Patients and methods: A total of 175 patients who had undergone resection of IPMNs with pre-operative EUS-FNA (EUS-FNA group) were analyzed and compared with 68 patients who had undergone resection with no pre-operative tissue sampling (No Sampling group). Patient characteristics, pathology, and frequency of peritoneal seeding after surgery were analyzed and compared. Peritoneal seeding was diagnosed based on pathology or image findings. Results: The two groups were comparable with respect to sex, age, follow-up duration, involvement of the pancreatic head, involvement of the main duct, grade of dysplasia, and size of histologically proven branch-duct IPMNs. Four patients (2.3 %) with invasive IPMN developed peritoneal seeding in the EUS-FNA group, whereas three (4.4 %, two with invasive IPMN and one with high-grade dysplasia) developed peritoneal seeding in the No Sampling group (P = 0.403). No peritoneal seeding was noted during surgery in these cases. Except for one patient in the EUS-FNA group, no spillage occurred during resection in these patients. Conclusions: In this cohort of patients undergoing resection of IPMN, the difference in the frequency of peritoneal seeding in the EUS-FNA group and the No Sampling group was not significant. C1 [Yoon, Won Jae; Daglilar, Ebubekir S.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Yoon, Won Jae] Inje Univ, Coll Med, Seoul Paik Hosp, Dept Internal Med, Seoul, South Korea. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org FU RedPath; Asuragen FX Dr. Brugge receives research funding from RedPath and Asuragen. NR 24 TC 19 Z9 20 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD MAY PY 2014 VL 46 IS 5 BP 382 EP 387 DI 10.1055/s-0034-1364937 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AI8HV UT WOS:000337153800003 PM 24619804 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Responsiveness to loop diuretics in heart failure SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID WORSENING RENAL-FUNCTION; OUTCOMES; RESISTANCE C1 [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 10 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2014 VL 35 IS 19 BP 1235 EP 1237 DI 10.1093/eurheartj/ehu121 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI6QB UT WOS:000336999400008 PM 24685713 ER PT J AU Valente, MAE Voors, AA Damman, K Van Veldhuisen, DJ Massie, BM O'Connor, CM Metra, M Ponikowski, P Teerlink, JR Cotter, G Davison, B Cleland, JGF Givertz, MM Bloomfield, DM Fiuzat, M Dittrich, HC Hillege, HL AF Valente, Mattia A. E. Voors, Adriaan A. Damman, Kevin Van Veldhuisen, Dirk J. Massie, Barrie M. O'Connor, Christopher M. Metra, Marco Ponikowski, Piotr Teerlink, John R. Cotter, Gad Davison, Beth Cleland, John G. F. Givertz, Michael M. Bloomfield, Daniel M. Fiuzat, Mona Dittrich, Howard C. Hillege, Hans L. TI Diuretic response in acute heart failure: clinical characteristics and prognostic significance SO EUROPEAN HEART JOURNAL LA English DT Article DE Diuretics; Heart failure; Diuretic resistance; Cardiorenal syndrome; Worsening renal function; Renal dysfunction; Prognosis; Mortality; Rehospitalization ID WORSENING RENAL-FUNCTION; CARDIORENAL SYNDROME; CONTINUOUS-INFUSION; BOLUS INJECTION; DYSPNEA RELIEF; ROLOFYLLINE; FUROSEMIDE; MORTALITY; ULTRAFILTRATION; RESISTANCE AB Aim Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome. Methods and results We examined diuretic response (defined as Delta weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable models. The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal. Conclusions Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study. C1 [Valente, Mattia A. E.; Voors, Adriaan A.; Damman, Kevin; Van Veldhuisen, Dirk J.; Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Massie, Barrie M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barrie M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Connor, Christopher M.; Fiuzat, Mona] Duke Univ, Med Ctr, Durham, NC USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Cotter, Gad; Davison, Beth] Momentum Res, Durham, NC USA. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard C.] Univ Iowa, Cardiovasc Res Ctr, Carver Coll Med, Iowa City, IA USA. [Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713 GZ Groningen, Netherlands. RP Voors, AA (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU Merck; NovaCardia; Amgen; BG Medicine; Biocontrol; Johnson and Johnson; Novartis; Sorbent; Vifor; Abbott; Biogen Idec; Corthera; Cytokinetics; Johnson and Johnson/ Scios; Relypsa; Solvay FX M.A.E.V, K. D., M. F., and H. L. H. have nothing to disclose. A. A. V. has received speaker and consultancy fees from Merck and NovaCardia. D.J.V.V. has received Board Membership fees from Amgen, BG Medicine, Biocontrol, Johnson and Johnson, Novartis, Sorbent, and Vifor. B. M. M. has received consulting fees from NovaCardia, sponsors of the study, and from Merck, that purchased the rights to rolofylline after the completion of the PROTECT pilot study. C.M.O.C. is a consultant to Merck. M. M. has received honoraria and reimbursements from NovaCardia, sponsors of the study, and from Merck, that purchased the rights to rolofylline after completion of the PROTECT pilot study. P. P. has received honoraria from Merck. J.R.T. has received research funds and consulting fees from Merck, the producer of rolofylline for the conduct of this study and has also received research funds and consulting fees from Abbott, Amgen, Biogen Idec, Corthera, Cytokinetics, Johnson and Johnson/ Scios, Novartis, Relypsa, and Solvay for research in related areas. G. C. and B. A. W. are employees of Momentum Research, Inc., which was contracted to perform work on the project by Merck & Co., Inc., J.G.F.C. was on the Steering Committee for the study, served on the Advisory Board for MSD, and received payments for both. M. M. G. has received institutional research support and served on a scientific Advisory Board for Merck. D. A. B. is an employee of Merck. H. C. D was an employee of NovaCardia and a consultant to Merck. NR 49 TC 36 Z9 37 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2014 VL 35 IS 19 BP 1284 EP + DI 10.1093/eurheartj/ehu065 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI6QB UT WOS:000336999400014 PM 24585267 ER PT J AU De Berardinis, B Januzzi, J Zampini, G Zancla, B Magrini, L Gaggin, H Nagurney, J Cardelli, P Di Stasio, E Di Somma, S AF De Berardinis, B. Januzzi, J. Zampini, G. Zancla, B. Magrini, L. Gaggin, H. Nagurney, J. Cardelli, P. Di Stasio, E. Di Somma, S. TI Short and long term mortality prognostic value of ST2 in patients with Acute Heart Failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [De Berardinis, B.; Zampini, G.; Zancla, B.; Magrini, L.; Cardelli, P.; Di Somma, S.] Univ Roma La Sapienza, St Andrea Hosp, Fac Med 2, I-00185 Rome, Italy. [Januzzi, J.; Gaggin, H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nagurney, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Di Stasio, E.] Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. 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 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2014 VL 16 SU 2 MA 96 BP 7 EP 8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH2QT UT WOS:000335966800009 ER PT J AU Vodovar, N Seronde, MF Laribi, S Nouira, S Samuel, JL Cohen-Solal, A Januzzi, JL Richards, AM Launay, JM Mabazaa, A AF Vodovar, NNicolas Seronde, M. F. Laribi, S. Nouira, S. Samuel, J. L. Cohen-Solal, A. Januzzi, J. L. Richards, A. M. Launay, J. M. Mabazaa, A. TI Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Vodovar, NNicolas; Samuel, J. L.] Natl Inst Hlth & Med Res INSERM Home, Paris, France. [Seronde, M. F.] Univ Hosp Jean Minjoz, Dept Cardiol, Besancon, France. [Laribi, S.] Hospital Lariboisiere, Dept Emmergency Med, Paris, France. [Nouira, S.] Fattouma Bourguiba Univ Hosp, Monastir, Tunisia. [Cohen-Solal, A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Januzzi, J. L.] Univ Otago Christchurch, Christchurch, New Zealand. RI Laribi, Said/D-5229-2014; Laribi, said/S-3693-2016 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 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2014 VL 16 SU 2 BP 112 EP 112 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH2QT UT WOS:000335966800380 ER PT J AU Gerhardt, LMS Hilgendorf, I Tan, TC Zirlik, A Scherer-Crosbie, M Hedrick, CC Libby, P Nahrendorf, M Weissleder, R Swirski, FK AF Gerhardt, L. M. S. Hilgendorf, I. Tan, T. C. Zirlik, A. Scherer-Crosbie, M. Hedrick, C. C. Libby, P. Nahrendorf, M. Weissleder, R. Swirski, F. K. TI Ly-6Chigh monocytes orchestrate both inflammatory and reparative phases of infarct healing and depend on nuclear orphan receptor Nur77 to promote optimal healing SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Gerhardt, L. M. S.; Hilgendorf, I.; Zirlik, A.] Univ Freiburg, Dept Cardiol, D-79106 Freiburg, Germany. [Tan, T. C.; Scherer-Crosbie, M.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Hedrick, C. C.] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Libby, P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2014 VL 16 SU 2 BP 213 EP 213 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH2QT UT WOS:000335966800742 ER PT J AU Lee, SJ AF Lee, Sei J. TI So Much Insulin, So Much Hypoglycemia SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID OLDER PATIENTS; RISK C1 [Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Lee, Sei J.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Bldg 1,Room 220F, San Francisco, CA 94121 USA. EM sei.lee@ucsf.edu FU NIA NIH HHS [K23 AG040779, P30 AG044281] NR 11 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2014 VL 174 IS 5 BP 686 EP 688 DI 10.1001/jamainternmed.2013.13307 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NS UT WOS:000336842700008 PM 24614940 ER PT J AU Makam, AN Auerbach, AD Steinman, MA AF Makam, Anil N. Auerbach, Andrew D. Steinman, Michael A. TI Blood Culture Use in the Emergency Department in Patients Hospitalized for Community-Acquired Pneumonia SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Makam, Anil N.] Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, Dallas, TX 75390 USA. [Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Makam, AN (reprint author), Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM anil.makam@utsouthwestern.edu OI Makam, Anil/0000-0001-7072-9946 FU NIA NIH HHS [K23 AG030999]; PHS HHS [T32HP19025-07-00] NR 7 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2014 VL 174 IS 5 BP 803 EP 806 DI 10.1001/jamainternmed.2013.13808 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NS UT WOS:000336842700030 PM 24614986 ER PT J AU Seabury, SA Chandra, A Jena, AB AF Seabury, Seth A. Chandra, Amitabh Jena, Anupam B. TI Gender Income Disparities Can Be Explained by Alternative Factors SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Seabury, Seth A.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA. [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Chandra, Amitabh] Harvard Univ, Harvard Kennedy Sch Govt, Cambridge, MA 02138 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2014 VL 174 IS 5 BP 822 EP 823 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NS UT WOS:000336842700044 PM 24799008 ER PT J AU Blanco, CL Moreira, AG McGill-Vargas, LL Anzueto, DG Nathanielsz, P Musi, N AF Blanco, Cynthia L. Moreira, Alvaro G. McGill-Vargas, Lisa L. Anzueto, Diana G. Nathanielsz, Peter Musi, Nicolas TI Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle SO JOURNAL OF ENDOCRINOLOGY LA English DT Article DE insulin; fetus; primate; muscle; glucocorticoid; corticosteroid; preterm ID BRONCHOPULMONARY DYSPLASIA; GLUCOSE-HOMEOSTASIS; PRETERM INFANTS; KINASE-B; GROWTH; DEXAMETHASONE; FETUS; GLUCOCORTICOIDS; HYPERGLYCEMIA; RESISTANCE AB We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 mg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals tomeasure the protein content and gene expression of insulin receptor beta (IRb; INSR), IRb Tyr 1361 phosphorylation (pIRb), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKTand AKT1 (respectively, 73 and 72% from 0.67 GA control, P! 0.001); IRb and pIRb were also decreased (respectively, 94 and 85%, P! 0.01) in themuscle of premature GCexposedfetusesbut not intermfetuses. GLUT1andGLUT4tendedto increasewithGCexposure in preterm animals (PZ0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P! 0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation. C1 [Blanco, Cynthia L.; Moreira, Alvaro G.; McGill-Vargas, Lisa L.; Anzueto, Diana G.] Univ Texas Hlth Sci Ctr San Antonio, Div Neonatol, Dept Pediat, San Antonio, TX 78229 USA. [Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, San Antonio, TX 78229 USA. [Musi, Nicolas] South Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. [Musi, Nicolas] Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Nathanielsz, Peter] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA. RP Blanco, CL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Neonatol, Dept Pediat, San Antonio, TX 78229 USA. EM blanco@uthscsa.edu OI Nathanielsz, Peter/0000-0001-8410-6280 FU Robert Wood Johnson Foundation; UTHSCSA CTSA [UL1RR025767]; American Diabetes Association; National Institutes of Health [HL52636, AG030979] FX This work was supported by grants from the Robert Wood Johnson Foundation (C L B), UTHSCSA CTSA (UL1RR025767; C L B), American Diabetes Association (C L B and N M), the National Institutes of Health (HL52636 to BPD resource Center, AG030979 to N M), P51RR13986 for facility support at the Southwest Foundation for Biomedical Research, the San Antonio Nathan Shock Center (N M), the UTHSCSA Executive Research Committee (N M), and the South Texas Health Research Center (N M). NR 40 TC 5 Z9 5 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 2014 VL 221 IS 2 BP 253 EP 260 DI 10.1530/JOE-13-0504 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI7WC UT WOS:000337110900012 PM 24756099 ER PT J AU Lai, PS Mita, C Thompson, BT AF Lai, P. S. Mita, C. Thompson, B. T. TI What is the clinical significance of pulmonary hypertension in acute respiratory distress syndrome? A review SO MINERVA ANESTESIOLOGICA LA English DT Review DE Hypertension, pulmonary; Acute lung injury; Respiratory distress syndrome, adult ID ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; END-EXPIRATORY PRESSURE; DEAD-SPACE FRACTION; RIGHT-VENTRICULAR FUNCTION; SEVERE ARDS; PROTECTIVE VENTILATION; MECHANICAL VENTILATION; VASCULAR DYSFUNCTION; CYCLIC CHANGES AB Elevated pulmonary arterial pressures appear to be a prominent feature of the acute respiratory distress syndrome (ARDS). Current clinical guidelines for the management of ARDS do not specifically address treatment of pulmonary hypertension or associated right ventricular dysfunction because the clinical significance of this entity remains unclear. Interpretation of elevated pulmonary arterial pressures, pulmonary vascular resistance, and transpulmonary gradient as well as signs of right ventricular dysfunction is confounded by the effects of positive pressure ventilation. There does not appear to be a consistent relationship between the diagnosis of pulmonary hypertension or right ventricular failure and mortality in patients with ARDS, but it is unclear if right ventricular failure contributes to the mortality risk per se or if the underlying cause of pulmonary hypertension, including intravascular micro and macro thrombosis, are simply markers for systemic dysregulation of coagulation and fibrinolysis that may lead to multiorgan failure in ARDS. While studies of pulmonary vasodilator therapies have not shown a mortality benefit in ARDS, such trials have targeted improved oxygenation rather than improved pulmonary hemodynamics so that the possible contribution of improved right ventricular function to better outcomes has not been directly tested in large trials. Future studies are needed to determine if treatment of pulmonary hypertension and associated right ventricular dysfunction will affect mortality in patients with ARDS. C1 [Lai, P. S.; Thompson, B. T.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. [Mita, C.] Harvard Univ, Countway Lib Med, Boston, MA 02115 USA. RP Lai, PS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch Suite 148,55 Fruit St, Boston, MA 02114 USA. EM plai@partners.org FU NHLBI NIH HHS [R01 HL060710, P01 HL108801, R01 HL112747]; NIEHS NIH HHS [K23 ES023700, F32 ES020082] NR 71 TC 3 Z9 4 U1 0 U2 3 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 EI 1827-1596 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD MAY PY 2014 VL 80 IS 5 BP 574 EP 585 PG 12 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA AI4XN UT WOS:000336870000008 PM 24193181 ER PT J AU Sepulcre, J AF Sepulcre, Jorge TI Integration of visual and motor functional streams in the human brain SO NEUROSCIENCE LETTERS LA English DT Article DE Visual streams; Motor streams; Visuo-motor integration; Brain network; Graph theory; Mirror neuron system ID HUMAN PARIETAL OPERCULUM; CEREBRAL-CORTEX; PREMOTOR CORTEX; MIRROR NEURONS; CONNECTIVITY; ORGANIZATION; AREAS; FMRI; RECOGNITION; EXECUTION AB A long-standing difficulty in brain research has been to disentangle how information flows across circuits composed by multiple local and distant cerebral areas. At the large-scale level, several brain imaging methods have contributed to the understanding of those circuits by capturing the covariance or coupling patterns of blood oxygen level-dependent (BOLD) activity between distributed brain regions. The hypothesis is that underlying information processes are closely associated to synchronized brain activity, and therefore to the functional connectivity structure of the human brain. In this study, we have used a recently developed method called stepwise functional connectivity analysis. Our results show that motor and visual connectivity merge in a multimodal integration network that links together perception, action and cognition in the human functional connectome. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Boston, MA USA. [Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Athinioula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Sepulcre, J (reprint author), Harvard Univ, 52 Oxford St,Northwest Bldg 280-02, Cambridge, MA 02138 USA. EM sepulcre@nmr.mgh.harvard.edu NR 52 TC 7 Z9 8 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 1 PY 2014 VL 567 BP 68 EP 73 DI 10.1016/j.neulet.2014.03.050 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AI6VL UT WOS:000337015000014 PM 24699175 ER PT J AU Gong, JJ Munoz, AR Chan, D Ghosh, R Kumar, AP AF Gong, Jingjing Munoz, Amanda R. Chan, Daniel Ghosh, Rita Kumar, Addanki P. TI STAT3 down regulates LC3 to inhibit autophagy and pancreatic cancer cell growth SO ONCOTARGET LA English DT Article DE Pancreatic cancer; Nexrutine (R); STAT3; inflammation; autophagy; LC3 ID PROSTATE-CANCER; BINDING-PROTEIN; DEATH; NEXRUTINE; APOPTOSIS; ACTIVATION; RECEPTOR; AKT; ADENOCARCINOMA; GLIOBLASTOMA AB The dismal 5-year survival (<5%) for pancreatic cancer (PanCA) underscores the need for developing effective therapeutic options. Recent studies from our laboratory have shown that Nexrutine (R) (Nx), a bark extract from Phellodendron amurense exhibits excellent anticancer activity in human pancreatic cancer cells through inhibition of inflammatory signaling via STAT3/NF kappa B/Cox-2. Given the apparent high oxidative stress and autophagic activity in pancreatic tumors, we investigated the potential of Nx to modulate autophagy, reactive oxygen species (ROS), and their crosstalk. Our results show that Nx inhibits autophagy and decreases ROS generation. Pharmacological inhibition of autophagy led to decreased ROS generation and proliferation with no significant effect on apoptosis. Further, using combination index analysis we also found that combination of late-stage autophagy inhibitor with Nx exhibited a moderate synergistic to additive effect. Additionally, genetic or pharmacological inactivation of STAT3 reduced LC3-II levels and expression indicating a possible role for STAT3 in transcriptional regulation of autophagy. Since both inflammatory and oxidative stress signaling activate STAT3, our data implicates that STAT3 plays a vital role in the regulation of autophagy through its contributions to the positive feedback loop between ROS and autophagy. Overall, our findings reveal an important role for STAT3/LC3/ROS in Nx-mediated anti-pancreatic cancer effects. C1 [Gong, Jingjing; Munoz, Amanda R.; Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Chan, Daniel] Univ Colorado, Div Med Oncol, Aurora, CO USA. [Ghosh, Rita; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kumar, AP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. EM kumara3@uthscsa.edu FU NCCAM [AT005513-01A1, AT 007448-01]; Veterans Affairs-Merit Award [1 I01 BX 000766-01]; NCI [1R01 CA149516]; TST predoctoral fellowship [8UL1 TR000149]; Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio through the National Cancer Institute [2P30 CA 054174-17] FX This work was supported in part by funds from NCCAM AT005513-01A1, AT 007448-01 and Veterans Affairs-Merit Award 1 I01 BX 000766-01(APK); NCI 1R01 CA149516 (RG); TST predoctoral fellowship 8UL1 TR000149 (JJ). We acknowledge support provided by flow cytometry and optical imaging cores of Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio through the National Cancer Institute support grant # 2P30 CA 054174-17 (APK). NR 63 TC 19 Z9 21 U1 0 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2014 VL 5 IS 9 BP 2529 EP 2541 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6FI UT WOS:000336966600016 PM 24796733 ER PT J AU Alam, M Rajabi, H Ahmad, R Jin, CN Kufe, D AF Alam, Maroof Rajabi, Hasan Ahmad, Rehan Jin, Caining Kufe, Donald TI Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells SO ONCOTARGET LA English DT Article DE MUC1; breast cancer; stem-like cells; mammospheres; tumorigenicity; NF-kappa B ID NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; MAMMARY-GLAND; STEM/PROGENITOR CELLS; MAMMOSPHERE CULTURE; ESTROGEN-RECEPTOR; CARCINOMA-CELLS; IN-VITRO; MECHANISMS AB The capacity of breast cancer cells to form mammospheres in non-adherent serum-free culture is used as a functional characteristic of the self-renewing stem-like cell population. The present studies demonstrate that silencing expression of the MUC1-C oncoprotein inhibits growth of luminal MCF-7 and HER2-overexpressing SKBR3 breast cancer cells as mammospheres. We also show that triple-negative MDAMB-468 breast cancer cells are dependent on MUC1-C for growth as mammospheres and tumor xenografts. Similar results were obtained when MUC1-C function was inhibited by expression of a MUC1-C(CQC -> AQA) mutant. Moreover, treatment with the MUC1-C inhibitor GO-203, a cell penetrating peptide that binds to the MUC1-C cytoplasmic domain and blocks MUC1-C function, confirmed the importance of this target for self-renewal. The mechanistic basis for these findings is supported by the demonstration that MUC1-C activates NF-kappa B, occupies the IL-8 promoter with NF-kappa B, and induces IL-8 transcription. MUC1-C also induces NF-kappa B-dependent expression of the IL-8 receptor, CXCR1. In concert with these results, targeting MUC1-C with GO-203 suppresses IL-8/CXCR1 expression and disrupts the formation of established mammospheres. Our findings indicate that MUC1-C contributes to the self-renewal of breast cancer cells by activating the NF-kappa B -> IL-8/CXCR1 pathway and that targeting MUC1-C represents a potential approach for the treatment of this population. C1 [Alam, Maroof; Rajabi, Hasan; Ahmad, Rehan; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute of the National Institutes of Health [CA97098, CA166480] FX Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers CA97098 and CA166480. NR 55 TC 27 Z9 28 U1 0 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2014 VL 5 IS 9 BP 2622 EP 2634 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6FI UT WOS:000336966600024 PM 24770886 ER PT J AU Choi, YE Battelli, C Watson, J Liu, J Curtis, J Morse, AN Matulonis, UA Chowdhury, D Konstantinopoulos, PA AF Choi, Young Eun Battelli, Chiara Watson, Jacqueline Liu, Joyce Curtis, Jennifer Morse, Alexander N. Matulonis, Ursula A. Chowdhury, Dipanjan Konstantinopoulos, Panagiotis A. TI Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells SO ONCOTARGET LA English DT Article DE Epithelial ovarian cancer; platinum; PARP inhibitors; Heat Shock Protein 90 inhibitors; homologous recombination ID NEGATIVE BREAST-CANCER; POLY(ADP-RIBOSE) POLYMERASE; CONNECTIVITY MAP; HSP90 INHIBITOR; PARP INHIBITION; RESISTANCE; EXPRESSION; MUTATIONS; CARCINOMA; GELDANAMYCIN AB The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more gamma H2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC. C1 [Choi, Young Eun; Watson, Jacqueline; Chowdhury, Dipanjan; Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Cambridge, MA 02138 USA. [Battelli, Chiara] Maine Ctr Canc Med, Scarborough, ME USA. [Liu, Joyce; Curtis, Jennifer; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Med Gynecol Oncol Program, Cambridge, MA 02138 USA. [Morse, Alexander N.] NYU, Global Inst Publ Hlth, New York, NY 10003 USA. RP Konstantinopoulos, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Cambridge, MA 02138 USA. EM panagiotis_konstantinopoulos@dfci.harvard.edu FU Ovarian Cancer Research Fund Program Project Grant FX This work was supported by the Ovarian Cancer Research Fund Program Project Grant to Dr Matulonis and Dr Konstantinopoulos. NR 33 TC 14 Z9 14 U1 1 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2014 VL 5 IS 9 BP 2678 EP 2687 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6FI UT WOS:000336966600028 PM 24798692 ER PT J AU Perandones, C Giugni, JC Calvo, DS Raina, GB Lopez, LDJ Volpini, V Zabetian, CP Mata, IF Caputo, M Corach, D Radrizzani, M Micheli, FE AF Perandones, C. Giugni, J. C. Calvo, D. S. Raina, G. B. De Jorge Lopez, L. Volpini, V. Zabetian, C. P. Mata, I. F. Caputo, M. Corach, D. Radrizzani, M. Micheli, F. E. TI Mosaicism of alpha-synuclein gene rearrangements: Report of two unrelated cases of early-onset parkinsonism SO PARKINSONISM & RELATED DISORDERS LA English DT Letter DE Parkinson's disease; alpha-Synuclein; Mosaicism; Gene multiplication ID DISEASE; MITOCHONDRIAL; DUPLICATION; DNA C1 [Perandones, C.; Giugni, J. C.; Calvo, D. S.; Raina, G. B.; Micheli, F. E.] Univ Buenos Aires, Parkinsons Dis & Movement Disorders Program, Hosp Clin, RA-1053 Buenos Aires, DF, Argentina. [Perandones, C.] Natl Agcy Labs & Hlth Inst Argentina ANUS, Buenos Aires, DF, Argentina. [De Jorge Lopez, L.; Volpini, V.] Inst Invest Biomed Bellvitge, Barcelona, Spain. [Zabetian, C. P.; Mata, I. F.] Univ Washington, Seattle, WA 98195 USA. [Zabetian, C. P.; Mata, I. F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Caputo, M.; Corach, D.] Univ Buenos Aires, Sch Pharm & Biochem, Serv Huellas Digit Genet, RA-1053 Buenos Aires, DF, Argentina. [Radrizzani, M.] Natl Univ San Martin, CONICET, Lab Neuro & Mol Cytogenet, Buenos Aires, DF, Argentina. RP Perandones, C (reprint author), Univ Buenos Aires, Parkinsons Dis & Movement Disorders Program, Hosp Clin, Ciudad Autonoma Buenos Aires C1120AAR, RA-1053 Buenos Aires, DF, Argentina. EM claudia.perandones@gmail.com OI Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [R01 NS065070] NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2014 VL 20 IS 5 BP 558 EP 561 DI 10.1016/j.Parkreldis.2013.11.014 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AI7LE UT WOS:000337071300017 PM 24552873 ER PT J AU Chasman, DI Anttila, V Buring, JE Ridker, PM Schurks, M Kurth, T AF Chasman, Daniel I. Anttila, Verneri Buring, Julie E. Ridker, Paul M. Schuerks, Markus Kurth, Tobias CA Int Headache Genetics Consortium TI Selectivity in Genetic Association with Sub-classified Migraine in Women SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; SUSCEPTIBILITY LOCI; PRIMARY PREVENTION; RISK LOCI; HEALTH; AURA; POPULATION; FEATURES; INHERITANCE AB Migraine can be sub-classified not only according to presence of migraine aura (MA) or absence of migraine aura (MO), but also by additional features accompanying migraine attacks, e. g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies (GWAS) have identified 12 independent loci at which single nucleotide polymorphisms (SNPs) are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of migraine. C1 [Chasman, Daniel I.; Buring, Julie E.; Ridker, Paul M.; Kurth, Tobias] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chasman, Daniel I.; Anttila, Verneri; Buring, Julie E.; Ridker, Paul M.; Kurth, Tobias] Harvard Univ, Sch Med, Boston, MA USA. [Anttila, Verneri] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Schuerks, Markus] Univ Hosp Essen, Dept Neurol, Essen, Germany. [Kurth, Tobias] INSERM, U897, Team Neuroepidemiol, Res Ctr Epidemiol & Biostat, Bordeaux, France. [Kurth, Tobias] Univ Bordeaux, Coll Hlth Sci, Bordeaux, France. RP Chasman, DI (reprint author), Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. EM dchasman@research.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Anttila, Verneri/0000-0002-0073-4675 FU National Heart, Lung, and Blood Institute [HL043851, HL080467]; National Cancer Institute [CA047988]; Amgen; National Institute of Neurological Disorders and Stroke [NS061836] FX The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, with collaborative scientific support and funding for genotyping provided by Amgen. Genetic analyses of migraine in WGHS have been supported by NS061836 from the National Institute of Neurological Disorders and Stroke. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 14 Z9 14 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2014 VL 10 IS 5 AR e1004366 DI 10.1371/journal.pgen.1004366 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AI8FP UT WOS:000337145100056 PM 24852292 ER PT J AU Kukurba, KR Zhang, R Li, X Smith, KS Knowles, DA Tan, MH Piskol, R Lek, M Snyder, M MacArthur, DG Li, JB Montgomery, SB AF Kukurba, Kimberly R. Zhang, Rui Li, Xin Smith, Kevin S. Knowles, David A. Tan, Meng How Piskol, Robert Lek, Monkol Snyder, Michael MacArthur, Daniel G. Li, Jin Billy Montgomery, Stephen B. TI Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues SO PLOS GENETICS LA English DT Article ID OF-FUNCTION VARIANTS; RNA-SEQ; REGULATORY VARIATION; GENE-EXPRESSION; SEQUENCING DATA; MUTATIONS; PATTERNS; DISEASE; CELLS; RARE AB Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants. C1 [Kukurba, Kimberly R.; Li, Xin; Smith, Kevin S.; Montgomery, Stephen B.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Kukurba, Kimberly R.; Zhang, Rui; Li, Xin; Smith, Kevin S.; Tan, Meng How; Piskol, Robert; Snyder, Michael; Li, Jin Billy; Montgomery, Stephen B.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Knowles, David A.; Montgomery, Stephen B.] Stanford Univ, Dept Comp Sci, Sch Med, Stanford, CA 94305 USA. [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Kukurba, KR (reprint author), Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. EM jin.billy.li@stanford.edu; smontgom@stanford.edu RI Tan, Meng How/M-8605-2015 FU DoD, Air Force Office of Scientific Research [32 CFR 168a]; Edward Mallinckrodt Jr. Foundation FX This research was conducted with government support under and awarded by DoD, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEG) Fellowship, 32 CFR 168a. SBM is funded by the Edward Mallinckrodt Jr. Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 17 Z9 17 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2014 VL 10 IS 5 AR e1004304 DI 10.1371/journal.pgen.1004304 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AI8FP UT WOS:000337145100010 PM 24786518 ER PT J AU Lee, H Lee, MY Bhang, SH Kim, BS Kim, YS Ju, JH Kim, KS Hahn, SK AF Lee, Hwiwon Lee, Min-Young Bhang, Suk Ho Kim, Byung-Soo Kim, Yun Seop Ju, Ji Hyeon Kim, Ki Su Hahn, Sei Kwang TI Hyaluronate-Gold Nanoparticle/Tocilizumab Complex for the Treatment of Rheumatoid Arthritis SO ACS NANO LA English DT Article DE gold nanoparticle; tocilizumab; hyaluronic acid; drug delivery; rheumatoid arthritis ID COLLAGEN-INDUCED ARTHRITIS; RECEPTOR INHIBITION; NANOPARTICLES; TOCILIZUMAB; THERAPY; ACID; DISEASE AB Rheumatoid arthritis (RA) is a chronic inflammatory immune disease causing the inflammation of synovial membrane and the articular cartilage destruction. In this work, hyaluronate gold nanoparticle/Tocilizumab (HA-AuNP/TCZ) complex was prepared for the treatment of RA. AuNP was used as a drug carrier with antiangiogenic effect. in is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and used as an immunosuppressive drug by Interfering IL-6 in the pathogenesis of RA. HA is known to have cartilage-protective and lubricant effects. HA was modified with cystamine via reductive amination, which was reduced with dithiothreitol (DTT) to prepare end-group thiolated HA (HA-SH). AuNP was chemically modified with HA-SH and physically modified with T. The formation of HA-AuNP/TCZ complex was corroborated by UV-vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The therapeutic effect of HA-AuNP/TCZ complex on RA was confirmed In collagen-induced arthritis (CIA) model mice by ELISA, histological, and Western blot analyses. C1 [Lee, Hwiwon; Lee, Min-Young; Kim, Yun Seop; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Bhang, Suk Ho; Kim, Byung-Soo] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151744, South Korea. [Ju, Ji Hyeon] Catholic Univ Korea, Coll Med, Dept Internal Med, Seoul 137701, South Korea. [Kim, Ki Su] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Kim, Ki Su] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Kyungbuk, South Korea. EM skhanb@postech.ac.kr RI Kim, Byung-Soo/O-2352-2013 FU Converging Research Center Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2009-0081871]; Midcareer Researcher Program through NRF - MEST [2012R1A2A2A06045773] FX This work was supported by the Converging Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0081871). This study was also supported by Midcareer Researcher Program through NRF grant funded by the MEST (No. 2012R1A2A2A06045773). NR 32 TC 21 Z9 21 U1 7 U2 86 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD MAY PY 2014 VL 8 IS 5 BP 4790 EP 4798 DI 10.1021/nn500685h PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA AI1UM UT WOS:000336640600069 PM 24730974 ER PT J AU Perrault, SD Shih, WM AF Perrault, Steven D. Shih, William M. TI Virus-Inspired Membrane Encapsulation of DNA Nanostructures To Achieve In Vivo Stability SO ACS NANO LA English DT Article DE DNA; nanotechnology; lipid bilayer; in vivo; nanostructure; imaging; immune; pharmacokinetics; biodistribution; PEG ID NANOSCALE SHAPES; FOLDING DNA; NANOPARTICLES; DELIVERY; OLIGONUCLEOTIDES; CLEARANCE; LIPOSOMES; RELEASE; ENZYME AB DNA nanotechnology enables engineering of molecular-scale devices with exquisite control over geometry and site-specific functionalization. This capability promises compelling advantages in advancing nanomedicine; nevertheless, instability in biological environments and innate immune activation remain as obstacles for in vivo application. Natural particle systems (i.e., viruses) have evolved mechanisms to maintain structural integrity and avoid immune recognition during infection, including encapsulation of their genome and protein capsid shell in a lipid envelope. Here we introduce virus-inspired enveloped DNA nanostructures as a design strategy for biomedical applications. Achieving a high yield of tightly wrapped unilamellar nanostructures, mimicking the morphology of enveloped virus particles, required precise control over the density of attached lipid conjugates and was achieved at 1 per similar to 180 nm(2). Envelopment of DNA nanostructures in PEGylated lipid bilayers conferred protection against nuclease digestion. Immune activation was decreased 2 orders of magnitude below controls, and pharmacokinetic bioavailability improved by a factor of 17. By establishing a design strategy suitable for biomedical applications, we have provided a platform for the engineering of sophisticated, translation-ready DNA nanodevices. C1 [Perrault, Steven D.; Shih, William M.] Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Perrault, Steven D.; Shih, William M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. EM William_Shih@dfci.harvard.edu FU Canadian Institutes of Health Research; Wyss Institute Technology Development Fellowship; NIH [1DP2OD004641]; ARO MURI [W911NF-12-1-0420]; Wyss Institute at Harvard FX We thank Dr. James Rothman and Jing Wang for their contribution of the oligonucleotide-lipid conjugate, Dr. Paul Gottlieb for his contribution of phi12 bacteriophage, Thomas Ferrante, Amanda Graveline, and Garry Cuneo for technical support, and Dr. Chenxiang Lin for discussions. S.D.P. holds a Canadian Institutes of Health Research Fellowship and a Wyss Institute Technology Development Fellowship, and this work was supported by NIH Grant 1DP2OD004641 and ARO MURI Grant W911NF-12-1-0420 to W.M.S., and by the Wyss Institute at Harvard. NR 38 TC 69 Z9 69 U1 5 U2 88 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD MAY PY 2014 VL 8 IS 5 BP 5132 EP 5140 DI 10.1021/nn5011914 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA AI1UM UT WOS:000336640600105 PM 24694301 ER PT J AU Malo, MS Moaven, O Muhammad, N Biswas, B Alam, SN Economopoulos, KP Gul, SS Hamarneh, SR Malo, NS Teshager, A Mohamed, MMR Tao, QS Narisawa, S Millan, JL Hohmann, EL Warren, HS Robson, SC Hodin, RA AF Malo, Madhu S. Moaven, Omeed Muhammad, Nur Biswas, Brishti Alam, Sayeda N. Economopoulos, Konstantinos P. Gul, Sarah Shireen Hamarneh, Sulaiman R. Malo, Nondita S. Teshager, Abeba Mohamed, Mussa M. Rafat Tao, Qingsong Narisawa, Sonoko Millan, Jose Luis Hohmann, Elizabeth L. Warren, H. Shaw Robson, Simon C. Hodin, Richard A. TI Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gut flora; microbiotal homeostasis; dysbiosis; intestinal loop model; CpG DNA; flagellin; lipopolysaccharides ID RANDOMIZED CONTROLLED-TRIAL; SACCHAROMYCES-BOULARDII; GASTROINTESTINAL-TRACT; ULCERATIVE-COLITIS; MICROBIAL ECOLOGY; TRICHURIS-SUIS; PREBIOTICS; PROBIOTICS; ATP; MAINTENANCE AB The intestinal microbiota plays a pivotal role in maintaining human health and well-being. Previously, we have shown that mice deficient in the brush-border enzyme intestinal alkaline phosphatase (IAP) suffer from dysbiosis and that oral IAP supplementation normalizes the gut flora. Here we aimed to decipher the molecular mechanism by which IAP promotes bacterial growth. We used an isolated mouse intestinal loop model to directly examine the effect of exogenous IAP on the growth of specific intestinal bacterial species. We studied the effects of various IAP targets on the growth of stool aerobic and anaerobic bacteria as well as on a few specific gut organisms. We determined the effects of ATP and other nucleotides on bacterial growth. Furthermore, we examined the effects of IAP on reversing the inhibitory effects of nucleotides on bacterial growth. We have confirmed that local IAP bioactivity creates a luminal environment that promotes the growth of a wide range of commensal organisms. IAP promotes the growth of stool aerobic and anaerobic bacteria and appears to exert its growth promoting effects by inactivating (dephosphorylating) luminal ATP and other luminal nucleotide triphosphates. We observed that compared with wild-type mice, IAP-knockout mice have more ATP in their luminal contents, and exogenous IAP can reverse the ATP-mediated inhibition of bacterial growth in the isolated intestinal loop. In conclusion, IAP appears to promote the growth of intestinal commensal bacteria by inhibiting the concentration of luminal nucleotide triphosphates. C1 [Malo, Madhu S.; Moaven, Omeed; Muhammad, Nur; Biswas, Brishti; Alam, Sayeda N.; Economopoulos, Konstantinos P.; Gul, Sarah Shireen; Hamarneh, Sulaiman R.; Malo, Nondita S.; Teshager, Abeba; Mohamed, Mussa M. Rafat; Tao, Qingsong; Hodin, Richard A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Narisawa, Sonoko; Millan, Jose Luis] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA USA. [Hohmann, Elizabeth L.; Warren, H. Shaw] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Infect Dis Unit, Boston, MA USA. [Hohmann, Elizabeth L.; Warren, H. Shaw] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Infect Dis Unit, Boston, MA USA. [Robson, Simon C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM rhodin@mgh.harvard.edu OI Moaven, Omeed/0000-0002-0560-0457; Economopoulos, Konstantinos/0000-0003-4856-0405 FU NIH [R01DK050623, R01DK047186]; MGH Department of Surgery; Bill and Melinda Gates Foundation; Nutrition Obesity Research Center at Harvard (NORCH, NIH) [P30 DK40561] FX This work was supported by NIH grants R01DK050623 and R01DK047186 to R. A. Hodin, a Junior Faculty Award to M. S. Malo from the MGH Department of Surgery, a Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation to M. S. Malo, and a Feasibility Grant from Nutrition Obesity Research Center at Harvard (NORCH, NIH Grant P30 DK40561) to M. S. Malo. NR 64 TC 21 Z9 21 U1 1 U2 17 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2014 VL 306 IS 10 BP G826 EP G838 DI 10.1152/ajpgi.00357.2013 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA AI4OH UT WOS:000336844200003 PM 24722905 ER PT J AU Pinello, L Lo Bosco, G Yuan, GC AF Pinello, Luca Lo Bosco, Giosue Yuan, Guo-Cheng TI Applications of alignment-free methods in epigenomics SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE epigenetics; nucleosome; DNA sequence; alignment-free method; machine learning ID EMBRYONIC STEM-CELLS; HUMAN GENOME; DNA METHYLATION; EPIGENETIC DOMAINS; CHROMATIN STATES; GENE-REGULATION; NUCLEOSOME; SEQUENCE; IDENTIFICATION; PREDICTION AB Epigenetic mechanisms play an important role in the regulation of cell type-specific gene activities, yet how epigenetic patterns are established and maintained remains poorly understood. Recent studies have supported a role of DNA sequences in recruitment of epigenetic regulators. Alignment-free methods have been applied to identify distinct sequence features that are associated with epigenetic patterns and to predict epigenomic profiles. Here, we review recent advances in such applications, including the methods to map DNA sequence to feature space, sequence comparison and prediction models. Computational studies using these methods have provided important insights into the epigenetic regulatory mechanisms. C1 [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lo Bosco, Giosue] Univ Palermo, Dept Math & Comp Sci, I-90133 Palermo, Italy. RP Lo Bosco, G (reprint author), Dipartimento Matemat & Informat, Via Archirafi 34, I-90123 Palermo, Italy. EM giosue.lobosco@unipa.it; gcyuan@jimmy.harvard.edu OI Lo Bosco, Giosue/0000-0002-1602-0693 FU NIH [HG005085] FX This research was supported by the NIH grant HG005085 to GY. NR 87 TC 2 Z9 3 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 EI 1477-4054 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAY PY 2014 VL 15 IS 3 SI SI BP 419 EP 430 DI 10.1093/bib/bbt078 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AI0IO UT WOS:000336530600008 PM 24197932 ER PT J AU Findlay, VJ Wang, C Watson, DK Camp, ER AF Findlay, V. J. Wang, C. Watson, D. K. Camp, E. R. TI Epithelial-to-mesenchymal transition and the cancer stem cell phenotype: insights from cancer biology with therapeutic implications for colorectal cancer SO CANCER GENE THERAPY LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; METASTATIC COLON-CANCER; TUMOR-INITIATING CELLS; ACUTE MYELOID-LEUKEMIA; E-CADHERIN EXPRESSION; BREAST-CANCER; RECTAL-CANCER; PANCREATIC-CANCER; DOWN-REGULATION; FACTOR RECEPTOR AB Although mortality from colorectal cancer (CRC) is decreasing, CRC is still the second highest cause of cancer-related deaths in America. Chemotherapy and radiation therapy now have central roles in our strategies to fight cancer, although we continue to lack novel strategies overcoming therapeutic resistance. Molecular mechanisms of therapeutic resistance in CRC continue to be under intense investigation. In this review, we highlight the recent evidence linking epithelial-to-mesenchynnal transition (EMT) with aggressive tumor biology as well as with the cancer stem cells (CSCs) across multiple organ systems including colon cancer. Furthermore, in the era of neo-adjuvant treatment, the clinical implications are concerning that our treatments may have the potential to induce more aggressive cancer cells through EMT, perhaps even generating CSCs more capable of metastasis and further resistant to treatment. This concern and potential reality highlights the critical need for further understanding the impact of clinical therapy on the pathobiology of cancer and further supports the need to therapeutically target the CSC. Besides serving as potential biomarkers for aggressive tumor biology and therapeutic resistance, EMT and CSC molecular pathways may highlight novel therapeutic targets as strategies for improving the response to conventional anti-neoplastic agents translating into improved oncologic outcomes. C1 [Findlay, V. J.; Watson, D. K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Wang, C.; Camp, E. R.] Med Univ S Carolina, Dept Surg, Div Surg Oncol, Charleston, SC 29425 USA. [Watson, D. K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Watson, D. K.; Camp, E. R.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Camp, E. R.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, Div Surg Oncol, 25 Courtenay Dr,Room 7018, Charleston, SC 29425 USA. EM campe@musc.edu FU National Institutes of Health [5R 1K08CA142904]; Hollings Cancer Center Translational Research Award; American Cancer Society: Institutional Research Grant FX This study was supported by National Institutes of Health, 5R 1K08CA142904 (ERC), Hollings Cancer Center Translational Research Award and American Cancer Society: Institutional Research Grant. NR 106 TC 41 Z9 43 U1 4 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAY PY 2014 VL 21 IS 5 BP 181 EP 187 DI 10.1038/cgt.2014.15 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA AI3QK UT WOS:000336776800002 PM 24787239 ER PT J AU Mela, T AF Mela, Theofanie TI Preface: Pacemakers and ICDs SO CARDIOLOGY CLINICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Pacer & ICD Clin, Boston, MA 02114 USA. RP Mela, T (reprint author), Massachusetts Gen Hosp, Pacer & ICD Clin, 75 Fruit St, Boston, MA 02114 USA. EM tmela@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 EI 1558-2264 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2014 VL 32 IS 2 BP XI EP XII DI 10.1016/j.ccl.2014.02.001 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI1TD UT WOS:000336636800001 PM 24793807 ER PT J AU Laserna, E Sibila, O Fernandez, JF Maselli, DJ Mortensen, EM Anzueto, A Waterer, G Restrepo, MI AF Laserna, Elena Sibila, Oriol Fernandez, Juan Felipe Maselli, Diego Jose Mortensen, Eric M. Anzueto, Antonio Waterer, Grant Restrepo, Marcos I. TI Impact of Macrolide Therapy in Patients Hospitalized With Pseudomonas aeruginosa Community-Acquired Pneumonia SO CHEST LA English DT Article ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; RANDOMIZED CONTROLLED-TRIAL; CARE-ASSOCIATED PNEUMONIA; GRAM-NEGATIVE BACILLI; RISK-FACTORS; BETA-LACTAM; MORTALITY; OUTCOMES; AZITHROMYCIN; EXACERBATIONS AB Background: Several studies have described a clinical benefit of macrolides due to their immunomodulatory properties in various respiratory diseases. We aimed to assess the effect of macrolide therapy on mortality in patients hospitalized for Pseudomonas aeruginosa community-acquired pneumonia (CAP). Methods: We performed a retrospective population-based study of > 150 hospitals in the US Veterans Health Administration. Patients were included if they had a diagnosis of CAP and P aeruginosa was identified as the causative pathogen. Patients with health-care-associated pneumonia and immunosuppression were excluded. Macrolide therapy was considered when administered within the first 48 h of admission. Univariate and multivariable analyses were performed using 30-day mortality as the dependent measure. Results: We included 402 patients with P aeruginosa CAP, of whom 171 (42.5%) received a macrolide during the first 48 h of admission. These patients were older and white. Macrolide use was not associated with lower 30-day mortality (hazard ratio, 1.14; 95% CI, 0.70-1.83; P=.5). In addition, patients treated with macrolides had no differences in ICU admission, use of mechanical ventilation, use of vasopressors, and length of stay (LOS) compared with patients not treated with macrolides. A subgroup analysis among patients with P aeruginosa CAP in the ICU showed no differences in baseline characteristics and outcomes. Conclusions: Macrolide therapy in the first 48 h of admission is not associated with decreased 30-day mortality, ICU admission, need for mechanical ventilation, and LOS in hospitalized patients with P aeruginosa CAP. Larger cohort studies should address the benefit of macrolides as immuno-modulators in patients with P aeruginosa CAP. C1 [Laserna, Elena] Hosp Comarcal de Mollet, Mollet Del Valles, Spain. [Laserna, Elena; Sibila, Oriol; Fernandez, Juan Felipe; Maselli, Diego Jose; Anzueto, Antonio; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Sibila, Oriol] Inst Invest Biomed St Pau, Barcelona, Spain. [Fernandez, Juan Felipe; Maselli, Diego Jose; Anzueto, Antonio; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Mortensen, Eric M.] North Texas Vet Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Waterer, Grant] Univ Western Australia, Perth, WA 6009, Australia. [Waterer, Grant] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst, Audrey L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Howard Hughes Medical Institute faculty [00378-001]; Department of Veterans Affairs Veterans Integrated Service Network 17 new faculty grant; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia (SOCAP); Fundacio Catalana de Pneumologia (FUCAP); Instituto de Salud Carlos III [BAE11/00102] FX This research was supported by Howard Hughes Medical Institute faculty [Start-up Grant 00378-001] and a Department of Veterans Affairs Veterans Integrated Service Network 17 new faculty grant. Drs Laserna and Sibila are supported by Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Societat Catalana de Pneumologia (SOCAP), and Fundacio Catalana de Pneumologia (FUCAP). Dr Sibila is supported by Instituto de Salud Carlos III [BAE11/00102]. Dr Restrepo's time is partially protected by K23-HL096054 from the National Heart, Lung, and Blood Institute. NR 33 TC 4 Z9 4 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2014 VL 145 IS 5 BP 1114 EP 1120 DI 10.1378/chest.13-1607 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AI0IZ UT WOS:000336532100029 PM 24458223 ER PT J AU Naik, AD AF Naik, Aanand D. TI Peering Inside the Black Box of Patient-Centered Care SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE Ediorials; health care quality, access, and evaluation; decision support techniques; patient-centered care; patient participation; shared decision making ID DECISION-MAKING; DIABETES-MELLITUS; ENDOSCOPY C1 [Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Ctr Innovat Qual Effectiveness & Safety IQuESt, Houston, TX USA. [Naik, Aanand D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Innovat Qual Effectiveness & Safety, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.edu FU HSRD VA [I01 HX000486] NR 18 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2014 VL 7 IS 3 BP 347 EP 349 DI 10.1161/CIRCOUTCOMES.114.001038 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3WQ UT WOS:000336796300001 PM 24823950 ER PT J AU Miedema, MD Duprez, DA Misialek, JR Blaha, MJ Nasir, K Silverman, MG Blankstein, R Budoff, MJ Greenland, P Folsom, AR AF Miedema, Michael D. Duprez, Daniel A. Misialek, Jeffrey R. Blaha, Michael J. Nasir, Khurram Silverman, Michael G. Blankstein, Ron Budoff, Matthew J. Greenland, Philip Folsom, Aaron R. TI Use of Coronary Artery Calcium Testing to Guide Aspirin Utilization for Primary Prevention: Estimates From the Multi-Ethnic Study of Atherosclerosis SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE aspirin; coronary disease; prevention ID LOW-DOSE ASPIRIN; RANDOMIZED-CONTROLLED-TRIALS; ALL-CAUSE MORTALITY; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; HEART-DISEASE; RISK-ASSESSMENT; EVENTS; POPULATION; CALCIFICATION AB Background-Aspirin for the primary prevention of coronary heart disease (CHD) is only recommended for individuals at high risk for CHD although the majority of CHD events occur in individuals who are at low to intermediate risk. Methods and Results-To estimate the potential of coronary artery calcium (CAC) scoring to guide aspirin use for primary prevention of CHD, we studied 4229 participants from the Multi-Ethnic Study of Atherosclerosis who were not on aspirin at baseline and were free of diabetes mellitus. Using data from median 7.6-year follow-up, 5-year number-needed-to-treat estimations were calculated by applying an 18% relative CHD reduction to the observed event rates. This was contrasted to 5-year number-needed-to-harm estimations based on the risk of major bleeding reported in an aspirin meta-analysis. Results were stratified by a 10% 10-year CHD Framingham Risk Score (FRS). Individuals with CAC >= 100 had an estimated net benefit with aspirin regardless of their traditional risk status (estimated 5-year number needed to treat of 173 for individuals <10% FRS and 92 for individuals >= 10% FRS, estimated 5-year number needed to harm of 442 for a major bleed). Conversely, individuals with zero CAC had unfavorable estimations (estimated 5-year number needed to treat of 2036 for individuals <10% FRS and 808 for individuals >= 10% FRS, estimated 5-year number needed to harm of 442 for a major bleed). Sex-specific and age-stratified analyses showed similar results. Conclusions-For the primary prevention of CHD, Multi-Ethnic Study of Atherosclerosis participants with CAC >= 100 had favorable risk/benefit estimations for aspirin use while participants with zero CAC were estimated to receive net harm from aspirin. C1 [Miedema, Michael D.] Minneapolis Heart Inst, Minneapolis, MN 55414 USA. [Miedema, Michael D.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Miedema, Michael D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Miedema, Michael D.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. [Duprez, Daniel A.] Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA. [Misialek, Jeffrey R.; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Blaha, Michael J.; Nasir, Khurram; Silverman, Michael G.] Johns Hopkins Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Nasir, Khurram] Baptist Hlth South Florida, Ctr Prevent & Wellness Res, Miami, FL USA. [Nasir, Khurram] Florida Int Univ, Dept Epidemiol, Robert Stempel Coll Publ Hlth, Miami, FL 33199 USA. [Nasir, Khurram] Herbert Wertheim Coll Med, Dept Med, Miami, FL USA. [Blankstein, Ron] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Budoff, Matthew J.] Los Angeles Biomed Res Inst Harbor UCLA, Torrance, CA USA. [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Greenland, Philip] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Miedema, MD (reprint author), Minneapolis Heart Inst, 800 East 28th St, Minneapolis, MN 55414 USA. EM mdm307@mail.harvard.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]; National Center for Research Resources [UL1-RR-024156, UL1-RR-025005] FX This research was supported by grants N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-RR-024156 and UL1-RR-025005 from the National Center for Research Resources. NR 41 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2014 VL 7 IS 3 BP 453 EP 460 DI 10.1161/CIRCOUTCOMES.113.000690 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3WQ UT WOS:000336796300016 PM 24803472 ER PT J AU Kaiser, J Bledowski, C Dietrich, J AF Kaiser, Jochen Bledowski, Christoph Dietrich, Joerg TI Neural correlates of chemotherapy-related cognitive impairment SO CORTEX LA English DT Review DE Chemotherapy; Cognitive deficits; Event-related potentials; Functional imaging; Review ID BREAST-CANCER SURVIVORS; HIGH-DOSE CHEMOTHERAPY; TEST-RETEST RELIABILITY; CENTRAL-NERVOUS-SYSTEM; CEREBRAL WHITE-MATTER; PRIMARY CNS LYMPHOMA; GAMMA-BAND ACTIVITY; ADJUVANT CHEMOTHERAPY; WORKING-MEMORY; PROTON SPECTROSCOPY AB Cancer survivors frequently experience cognitive deficits following chemotherapy. The most commonly affected functions include memory, attention and executive control. The present paper reviews animal research and clinical studies including event-related potential (ERP) and neuroimaging investigations of chemotherapy-related changes of brain structure and function. In rodents, chemotherapeutic substances have been shown to damage neural precursor cells and white matter tracts and are associated with impairments of learning and memory. Structural and functional changes associated with chemotherapy have also been observed in humans. Structural imaging has revealed gray and white matter volume reductions and altered white matter microstructure. Functional studies using either ERPs or hemodynamic imaging have shown that chemotherapy alters the activation patterns of cortical networks involved in higher cognitive functions. Collectively, these findings support the existence of the "chemobrain" phenomenon beyond the patients' subjective reports. However, the rather small number of studies and methodological limitations of some of the pioneering investigations call for further research of high methodological quality, including larger numbers of subjects with appropriate controls to delineate the temporal and spatial pattern of chemotherapy-associated central nervous system (CNS) toxicity. Brain activation studies in humans might systematically vary task difficulty levels to distinguish between compensatory hyper-activations on the one hand and deficient recruitment of resources on the other hand. Integrative functions could be tested by connectivity analyses using both electrophysiological and hemodynamic measures. The ultimate goal should be the development of cognitive-behavioral and pharmacological interventions to reduce the cognitive side effects of the medically indispensable but neurotoxic chemotherapeutic treatments. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kaiser, Jochen; Bledowski, Christoph] Goethe Univ Frankfurt, Fac Med, Inst Med Psychol, D-60528 Frankfurt, Germany. [Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr,Dept Neurol, Boston, MA USA. [Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. RP Kaiser, J (reprint author), Goethe Univ Frankfurt, Fac Med, Inst Med Psychol, Heinrich Hoffmann Str 10, D-60528 Frankfurt, Germany. EM j.kaiser@med.uni-frankfurt.de NR 143 TC 15 Z9 15 U1 3 U2 30 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD MAY PY 2014 VL 54 BP 33 EP 50 DI 10.1016/j.cortex.2014.01.010 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AH9LW UT WOS:000336464900004 PM 24632463 ER PT J AU Kumar, V Alt, FW Oksenych, V AF Kumar, Vipul Alt, Frederick W. Oksenych, Valentyn TI Reprint of "Functional overlaps between XLF and the ATM-dependent DNA double strand break response" SO DNA REPAIR LA English DT Article DE Cernunnos; ATM; DNA-PKcs; NHEJ; V(D)J recombination; 53BP1 ID CLASS-SWITCH RECOMBINATION; SIGNAL JOINT FORMATION; INCREASED GENOMIC INSTABILITY; LEAKY SCID PHENOTYPE; V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; LIGASE-IV; PROTEIN-KINASE; HISTONE H2AX; DAMAGE-RESPONSE AB Developing B and T lymphocytes generate programmed DNA double strand breaks (DSBs) during the V(D)J recombination process that assembles exons that encode the antigen-binding variable regions of antibodies. In addition, mature B lymphocytes generate programmed DSBs during the immunoglobulin heavy chain (IgH) class switch recombination (CSR) process that allows expression of different antibody heavy chain constant regions that provide different effector functions. During both V(D)J recombination and CSR, DSB intermediates are sensed by the ATM-dependent DSB response (DSBR) pathway, which also contributes to their joining via classical non-homologous end-joining (C-NHEJ). The precise nature of the interplay between the DSBR and C-NHEJ pathways in the context of DSB repair via C-NHEJ remains under investigation. Recent studies have shown that the XLF C-NHEJ factor has functional redundancy with several members of the ATM-dependent DSBR pathway in C-NHEJ, highlighting unappreciated major roles for both XLF as well as the DSBR in V(D)J recombination, CSR and C-NHEJ in general. In this review, we discuss current knowledge of the mechanisms that contribute to the repair of DSBs generated during B lymphocyte development and activation with a focus on potential functionally redundant roles of XLF and ATM-dependent DSBR factors. (C) 2014 Elsevier B.V. C1 [Kumar, Vipul; Alt, Frederick W.; Oksenych, Valentyn] Harvard Univ, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston Childrens Hosp,Dept Genet,Med Sch, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston Childrens Hosp,Dept Genet,Med Sch, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; oksenych@gmail.com OI Oksenych, Valentyn/0000-0002-5088-3791 FU NIH [GM007226-38, AI076210] FX V.K. is supported by an NIH T32 training grant GM007226-38. F.W.A. is supported by NIH grant AI076210. F.W.A. is an Investigator of the Howard Hughes Medical Institute. NR 148 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD MAY PY 2014 VL 17 SI SI BP 52 EP 63 DI 10.1016/j.dnarep.2014.04.004 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA AI4IS UT WOS:000336829500007 PM 24767946 ER PT J AU Sheth, SA Aronson, JP Shafi, MM Phillips, HW Velez-Ruiz, N Walcott, BP Kwon, CS Mian, MK Dykstra, AR Cole, A Eskandar, EN AF Sheth, Sameer A. Aronson, Joshua P. Shafi, Mouhsin M. Phillips, H. Wesley Velez-Ruiz, Naymee Walcott, Brian P. Kwon, Churl-Su Mian, Matthew K. Dykstra, Andrew R. Cole, Andrew Eskandar, Emad N. TI Utility of foramen ovale electrodes in mesial temporal lobe epilepsy SO EPILEPSIA LA English DT Article DE Foramen ovale; Depth electrodes; Epilepsy; Mesial temporal sclerosis ID SURGERY; ONSET; LOCALIZATION; RECORDINGS; SEIZURES; SCALP; LONG AB ObjectivesTo determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE). MethodsWe identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision. ResultsForty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5months). SignificanceMore than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . C1 [Sheth, Sameer A.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Neurosurg, New York, NY USA. [Aronson, Joshua P.; Phillips, H. Wesley; Walcott, Brian P.; Kwon, Churl-Su; Mian, Matthew K.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Shafi, Mouhsin M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Epilepsy,Dept Neurol, Boston, MA 02215 USA. [Velez-Ruiz, Naymee] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Dykstra, Andrew R.; Cole, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Sheth, SA (reprint author), Neurol Inst, 4th Floor,710 W 168th St, New York, NY 10032 USA. EM sheth@post.harvard.edu OI Cole, Andrew/0000-0002-0828-826X FU KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources and National Center for Advancing Translational Sciences, National Institutes of Health (NIH)) [8KL2TR000168-05] FX MMS is supported by a KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and National Center for Advancing Translational Sciences, National Institutes of Health (NIH) Award 8KL2TR000168-05). NR 22 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD MAY PY 2014 VL 55 IS 5 BP 713 EP 724 DI 10.1111/epi.12571 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA AI1PK UT WOS:000336623200018 PM 24605889 ER PT J AU Srinivasa, S Grinspoon, SK AF Srinivasa, Suman Grinspoon, Steven K. TI MECHANISMS IN ENDOCRINOLOGY Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Review ID NAIVE HIV-1-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE INHIBITORS; ONCE-DAILY DARUNAVIR/RITONAVIR; RANDOMIZED CONTROLLED-TRIAL; INDUCED MITOCHONDRIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE RISK; BOOSTED PROTEASE INHIBITORS; MULTICENTER AIDS COHORT; NON-INFERIORITY TRIAL; ENDOTHELIAL FUNCTION AB In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks. C1 [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@mgh.harvard.edu FU Bristol-Myers Squibb; EMD Serono FX Dr Grinspoon has received research funding from Bristol-Myers Squibb and EMD Serono and served as a consultant for Navidea Inc., Aileron, Inc., and BMS/AstraZeneca unrelated to this manuscript. NR 112 TC 12 Z9 12 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAY PY 2014 VL 170 IS 5 BP R185 EP R202 DI 10.1530/EJE-13-0967 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI2ZQ UT WOS:000336728100005 PM 24523497 ER PT J AU Berkowitz, SA Karter, AJ Lyles, CR Liu, JY Schillinger, D Adler, NE Moffet, HH Sarkar, U AF Berkowitz, Seth A. Karter, Andrew J. Lyles, Courtney R. Liu, Jennifer Y. Schillinger, Dean Adler, Nancy E. Moffet, Howard H. Sarkar, Urmimala TI Low Socioeconomic Status is Associated with Increased Risk for Hypoglycemia in Diabetes Patients: the Diabetes Study of Northern California (DISTANCE) SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Socioeconomic factors; hypoglycemia; diabetes mellitus; vulnerable populations ID BLOOD-GLUCOSE CONTROL; QUALITY-OF-LIFE; OLDER-ADULTS; GLYCEMIC CONTROL; FOOD INSECURITY; MELLITUS; HEALTH; POPULATION; COMPLICATIONS; DISPARITIES AB Background. Social risk factors for hypoglycemia are not well understood. Methods. Cross-sectional analysis from the DISTANCE study, a multi-language, ethnically-stratified random sample of adults in the Kaiser Permanente Northern California diabetes registry, conducted in 2005-2006 (response rate 62%). Exposures were income and educational attainment; outcome was patient report of severe hypoglycemia. To test the association, we used multivariable logistic regression to adjust for demographic and clinical factors. Results. 14,357 patients were included. Reports of severe hypoglycemia were common (11%), and higher in low-income vs. high-income (16% vs. 8.8) and low-education vs. high-education (11.9% vs. 8.9%) groups. In multivariable analysis, incomes of less than $15,000 (OR 1.51 95%CI 1.19-1.91), $15,000-$24,999 (OR 1.57 95%CI 1.27-1.94), and high school or less education (OR 1.42, 95%CI 1.24-1.63) were associated with increased hypoglycemia, similar to insulin use (OR 1.44 95%CI 1.19-1.74). Conclusions. Low income and educational attainment are important risk factors for hypoglycemia. C1 [Berkowitz, Seth A.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Karter, Andrew J.; Liu, Jennifer Y.; Moffet, Howard H.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Lyles, Courtney R.; Schillinger, Dean; Sarkar, Urmimala] Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA. [Lyles, Courtney R.; Schillinger, Dean; Sarkar, Urmimala] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA 94143 USA. [Adler, Nancy E.] Univ Calif San Francisco, Ctr Hlth & Community, San Francisco, CA 94143 USA. [Schillinger, Dean] Calif Dept Publ Hlth, Calif Diabet Program, Sacramento, CA USA. [Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Berkowitz, SA (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM SABerkowitz@partners.org OI Berkowitz, Seth/0000-0003-1030-4297 FU NICHD NIH HHS [R01 HD046113, R01 HD46113]; NIDDK NIH HHS [P30 DK092924, R01 DK065664, R01 DK081796]; PHS HHS [T32HP10251] NR 44 TC 11 Z9 11 U1 0 U2 9 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2014 VL 25 IS 2 BP 478 EP 490 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AH7VJ UT WOS:000336343100005 PM 24858863 ER PT J AU Allen, JD Leyva, B Torres, MI Ospino, H Tom, L Rustan, S Bartholomew, A AF Allen, Jennifer D. Leyva, Bryan Torres, Maria Idali Ospino, Hosffman Tom, Laura Rustan, Sarah Bartholomew, Amanda TI Religious Beliefs and Cancer Screening Behaviors among Catholic Latinos: Implications for Faith-based Interventions SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Religion; spirituality; Catholicism; Hispanic; Latino; health; cancer screening; faith-based intervention; health promotion; qualitative research ID AFRICAN-AMERICAN-WOMEN; COLORECTAL-CANCER; MEXICAN-AMERICANS; HEALTH-CARE; EXPLANATORY MODELS; PROSTATE-CANCER; HISPANIC-WOMEN; SOCIAL TIES; LOW-INCOME; CHURCH AB Although most U.S. Latinos identify as Catholic, few studies have focused on the influence of this religious tradition on health beliefs among this population. This study explores the role of Catholic religious teachings, practices, and ministry on cancer screening knowledge, attitudes, and behaviors among Latinos. Eight focus groups were conducted with 67 Catholic Latino parishioners in Massachusetts. Qualitative analysis provided evidence of strong reliance on faith, God, and parish leaders for health concerns. Parishes were described as vital sources of health and social support, playing a central role in the community's health. Participants emphasized that their religious beliefs promote positive health behaviors and health care utilization, including the use of cancer screening services. In addition, they expressed willingness to participate in cancer education programs located at their parishes and provided practical recommendations for implementing health programs in parishes. Implications for culturally appropriate health communication and faith-based interventions are discussed. C1 [Allen, Jennifer D.; Tom, Laura; Bartholomew, Amanda] Dana Farber Canc Inst, Boston, MA 02215 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Torres, Maria Idali; Rustan, Sarah] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Phyllis F Cantor Ctr Nursing Res & Patient Care S, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCCDPHP CDC HHS [U48 DP001946, U48DP001946]; NCI NIH HHS [U54 CA156732, U54CA156732]; NIMHD NIH HHS [R21 MD005976] NR 109 TC 4 Z9 4 U1 3 U2 18 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2014 VL 25 IS 2 BP 503 EP 526 PG 24 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AH7VJ UT WOS:000336343100007 PM 24858865 ER PT J AU Kangovi, S Levy, K Barg, FK Carter, T Long, JA Grande, D AF Kangovi, Shreya Levy, Kathryn Barg, Frances K. Carter, Tamala Long, Judith A. Grande, David TI Perspectives of Older Adults of Low Socioeconomic Status on the Post-hospital Transition SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Low socioeconomic status; dually-eligible individuals; post-hospital transition; disparities ID RANDOMIZED CONTROLLED-TRIAL; LOW-INCOME SENIORS; HEART-FAILURE; MEDICARE BENEFICIARIES; CARE; READMISSION; EXPERIENCES; MORTALITY; QUALITY; HEALTH AB Background. Older adults of low socioeconomic status are at high risk for poor post-hospital outcomes. Design. A qualitative researcher, who was also an outreach worker from the West Philadelphia community, conducted in-depth interviews with 25 participants within 30 days of their hospital discharge. Participants. Eligible participants were: 1) residents of high-poverty ZIP codes; 2) dually eligible for Medicare and Medicaid; 3) had capacity or a caregiver who could be interviewed as a proxy; 4) general medicine or cardiology patients. Results. Participants were unable to access the care and accommodations needed to cope with post-hospital frailty. As a result, medical disability was amplified by socioeconomic disability. Participants were ashamed of the resulting loss of control and had difficulty asking for help, particularly from potential supports who were perceived as emotionally controlling or judgmental. Conclusion. Strategies that address socioeconomic stressors of hospitalization and provide empathic support may improve the post-hospital transition for these high-risk individuals. C1 [Kangovi, Shreya; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kangovi, Shreya] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Levy, Kathryn; Long, Judith A.; Grande, David] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Long, Judith A.; Grande, David] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Barg, Frances K.; Carter, Tamala] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kangovi, S (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kangovi@upenn.edu NR 46 TC 1 Z9 1 U1 0 U2 9 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2014 VL 25 IS 2 BP 746 EP 756 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AH7VJ UT WOS:000336343100025 PM 24858883 ER PT J AU Lyerly, MJ Albright, KC Boehme, AK Shahripour, RB Houston, JT Rawal, PV Kapoor, N Alvi, M Sisson, A Alexandrov, AW Alexandrov, AV AF Lyerly, Michael J. Albright, Karen C. Boehme, Amelia K. Shahripour, Reza Bavarsad Houston, James T. Rawal, Pawan V. Kapoor, Niren Alvi, Muhammad Sisson, April Alexandrov, Anne W. Alexandrov, Andrei V. TI Safety of Protocol Violations in Acute Stroke tPA Administration SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Acute ischemic stroke; thrombolysis; patient safety; protocol violation; symptomatic intracerebral hemorrhage ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; OFF-LABEL THROMBOLYSIS; INTRAVENOUS THROMBOLYSIS; HEMORRHAGIC COMPLICATIONS; ALTEPLASE; US AB Background: Intravenous (IV) tissue plasminogen activator remains the only approved therapy for acute ischemic stroke (AIS) in the United States; however, less than 10% of patients receive treatment. This is partially because of the large number of contraindications, narrow treatment window, and physician reluctance to deviate from these criteria. Methods: We retrospectively analyzed consecutive patients who received IV thrombolysis at our stroke center for National Institute of Neurological Disorders and Stroke (NINDS) protocol violations and rates of symptomatic intracerebral hemorrhage (sICH). Other outcome variables included systemic hemorrhage, modified Rankin Scale at discharge, and discharge disposition. Results: A total of 212 patients were identified in our stroke registry between 2009 and 2011 and included in the analysis. Protocol violations occurred in 76 patients (36%). The most common violations were thrombolysis beyond 3 hours (26%), aggressive blood pressure management (15%), elevated prothrombin time (PT) or partial thromboplastin time (PTT) (6.6%), minor or resolving deficits (4.2%), unclear time of onset (3.9%), and stroke within 3 months (3%). There were no significant differences in any of the safety outcomes or discharge disposition between patients with or without protocol violations. Controlling for age, National Institutes of Health Stroke Scale on admission, and glucose on admission, there was no significant increase in sICH (odds ratio: 3.8; 95% confidence interval: .37-38.72) in the patients who had protocol violations. Conclusions: Despite more than one third of patients receiving thrombolysis with protocol violations, overall rates of hemorrhage remained low and did not differ from those who did not have violations. Our data support the need to expand access to thrombolysis in AIS patients. C1 [Lyerly, Michael J.; Albright, Karen C.; Boehme, Amelia K.; Shahripour, Reza Bavarsad; Houston, James T.; Rawal, Pawan V.; Kapoor, Niren; Alvi, Muhammad; Sisson, April; Alexandrov, Anne W.; Alexandrov, Andrei V.] Univ Alabama Birmingham, Dept Neurol, Sch Med, Birmingham, AL 35294 USA. [Lyerly, Michael J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Albright, Karen C.; Boehme, Amelia K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Albright, Karen C.] Univ Alabama Birmingham, Hlth Serv, Birmingham, AL 35294 USA. [Albright, Karen C.] Univ Alabama Birmingham, Outcomes Res Ctr Outcome & Effectiveness Res & Ed, Birmingham, AL 35294 USA. [Albright, Karen C.] Univ Alabama Birmingham, Ctr Excellence Comparat Effectiveness Res Elimina, Minor Hlth & Hlth Dispar Res Ctr, Birmingham, AL 35294 USA. [Alexandrov, Anne W.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL 35294 USA. RP Lyerly, MJ (reprint author), Univ Alabama Birmingham, Dept Neurol, Stroke Program, 1813 6th Ave S,RWUH M226, Birmingham, AL 35294 USA. EM mjlyerly@uab.edu OI Alexandrov, Andrei V/0000-0001-8871-1023; Boehme, Amelia/0000-0002-7109-6025; Lyerly, Michael/0000-0003-4236-1018 FU Agency for Healthcare Research and Quality [5 T32 HS013852-10]; National Institute on Minority Health and Health Disparities [3 P60 MD000502-08S1]; National Institutes of Health; American Heart Association [13PRE13830003] FX K.C.A. is supported by award numbers 5 T32 HS013852-10 from The Agency for Healthcare Research and Quality, 3 P60 MD000502-08S1 from The National Institute on Minority Health and Health Disparities, and National Institutes of Health. A.K.B. is supported by award 13PRE13830003 from the American Heart Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality, American Heart Association, or the National Institutes of Health. NR 25 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY-JUN PY 2014 VL 23 IS 5 BP 855 EP 860 DI 10.1016/j.jstrokecerebrovasdis.2013.07.019 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AH9SI UT WOS:000336482000026 PM 23954609 ER PT J AU Walcott, BP Kamel, H Castro, B Kimberly, WT Sheth, KN AF Walcott, Brian P. Kamel, Hooman Castro, Brandyn Kimberly, W. Taylor Sheth, Kevin N. TI Tracheostomy after Severe Ischemic Stroke: A Population-based Study SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Brain edema; brain injuries; decompressive craniectomy; intracranial pressure; stroke; tracheostomy ID VENTILATOR-ASSOCIATED PNEUMONIA; CEREBRAL-ARTERY INFARCTION; QUALITY-OF-CARE; MECHANICAL VENTILATION; INTENSIVE-CARE; RISK-FACTORS; ADMINISTRATIVE DATA; HEMISPHERIC STROKE; COPENHAGEN-STROKE; CONTROLLED-TRIAL AB Background: Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke. Methods: Using the Nationwide Inpatient Sample database from 2007 to 2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates. Results: In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% confidence interval [CI], 1.2-1.4%), with a 1.3% (95% CI, 1.1-1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26-39%) rate in the surgical treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (odds ratio, 3.95; 95% CI, 1.95-6.91). Conclusions: Tracheostomy is common after decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Kamel, Hooman] Weill Cornell Med Coll, Dept Neurol, New York, NY USA. [Castro, Brandyn] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Rm 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU American Academy of Neurology; Brain Aneurysm Foundation FX The funding for this research was provided by the American Academy of Neurology (BC) and the Brain Aneurysm Foundation (BPW). NR 59 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY-JUN PY 2014 VL 23 IS 5 BP 1024 EP 1029 DI 10.1016/j.jstrokecerebrovasdis.2013.08.019 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AH9SI UT WOS:000336482000047 PM 24103666 ER PT J AU Montagnini, M Kaiser, RM Clark, PG Dodd, MA Goodwin, C Periyakoil, VS Ramsel, D Sanchez-Reilly, SE Semla, TP Smith, H Supiano, K Tsukuda, RA Zeiss, A OngChansanchai, LC AF Montagnini, Marcos Kaiser, Robert M. Clark, Phillip G. Dodd, Melanie A. Goodwin, Carol Periyakoil, Vyjeyanthi S. Ramsel, Dee Sanchez-Reilly, Sandra E. Semla, Todd P. Smith, Heather Supiano, Katherine Tsukuda, Ruth Ann Zeiss, Antonette OngChansanchai, Li-Chia CA Partnership Hlth Aging Workgrp Int TI Position Statement on Interdisciplinary Team Training in Geriatrics: An Essential Component of Quality Health Care for Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE interdisciplinary; team training; geriatrics education ID RANDOMIZED CONTROLLED-TRIAL; ALL-INCLUSIVE CARE; INTERPROFESSIONAL EDUCATION; PROGRAM; MANAGEMENT; LESSONS; MODEL; PACE AB Interdisciplinary team training (IDT) is an important component of ensuring quality geriatric care delivery, which can be complex and time intensive, requiring coordination of many medical, psychosocial, and therapeutic interventions and professionals. The Partnership for Health in Aging (PHA), a loose coalition of more than 30 organizations representing healthcare professionals who care for older adults supported by the American Geriatrics Society, identified IDT training in geriatrics as a priority area in addressing the geriatrics workforce shortage described in the 2008 Institute of Medicine report, Retooling for An Aging America: Building the Health Care Workforce. A PHA Workgroup on Interdisciplinary Team Training in Geriatrics was convened to review the literature focused on geriatrics IDT training and to develop a position statement that would inform and influence groups involved in the development and expansion of academic and continuing education programs in IDT training, including professional associations, credentialing and licensing bodies, accreditation organizations, and university administrators. There are significant challenges to expanding the development and implementation of geriatrics IDT training for health professionals, and such training will be successful only with substantial and sustained advocacy from the above professional groups. C1 [Montagnini, Marcos] Univ Michigan, VA Ann Arbor Healthcare Syst, GRECC, Ann Arbor, MI 48109 USA. [Kaiser, Robert M.] George Washington Univ, Sch Med, DC Vet Affairs Med Ctr, Washington, DC USA. [Clark, Phillip G.] Univ Rhode Isl, Providence, RI 02908 USA. [Dodd, Melanie A.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Goodwin, Carol] Amer Geriatr Soc, New York, NY USA. [Periyakoil, Vyjeyanthi S.] Stanford Univ, Sch Med, Palo Alto Hlth Care Syst, Stanford, CA 94305 USA. [Ramsel, Dee] Med Coll Wisconsin, VHA Natl Ctr Org Dev, Milwaukee, WI 53226 USA. [Sanchez-Reilly, Sandra E.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Smith, Heather] Med Coll Wisconsin, Clement J Zablocki VAMC, Milwaukee, WI 53226 USA. [Supiano, Katherine] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Tsukuda, Ruth Ann] Portland VA Med Ctr, Portland, OR USA. [Zeiss, Antonette] Dept Vet Affairs, VA Cent Off, Washington, DC USA. RP Montagnini, M (reprint author), VA Ann Arbor Healthcare Syst, GRECC, 2215 Fuller Rd 11-G, Ann Arbor, MI 48105 USA. EM mmontag@umich.edu OI Supiano, Katherine/0000-0001-7267-7705 FU MedEd Portal Interprofessional Educational Collaborative Collection FX Dr. Dodd has received grant support from MedEd Portal Interprofessional Educational Collaborative Collection and a 10% salary release from Donald W. Reynolds Foundation Next Steps in Physician's Training in Geriatrics Grant. NR 48 TC 10 Z9 10 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2014 VL 62 IS 5 BP 961 EP 965 DI 10.1111/jgs.12822 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AH8JY UT WOS:000336385300027 ER PT J AU Heringa, SM Walraven, I Moll, AC van den Berg, E Nijpels, G Stehouwer, CDA Reijmer, YD Kappelle, LJ Dekker, JM Biessels, GJ AF Heringa, Sophie M. Walraven, Iris Moll, Annette C. van den Berg, Esther Nijpels, Giel Stehouwer, Coen D. A. Reijmer, Yael D. Kappelle, L. J. Dekker, Jacqueline M. Biessels, Geert Jan TI VASCULAR RETINOPATHY IN RELATION TO COGNITIVE FUNCTIONING IN AN OLDER POPULATION-THE HOORN STUDY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID DEMENTIA; ABNORMALITIES; ASSOCIATIONS C1 [Heringa, Sophie M.; van den Berg, Esther; Kappelle, L. J.; Biessels, Geert Jan] Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Walraven, Iris; Moll, Annette C.] Vrije Univ Amsterdam, Med Ctr, Dept Ophthalmol, Inst Res Extramural Med,EMGO Inst, Amsterdam, Netherlands. [van den Berg, Esther] Univ Utrecht, Helmholtz Inst, Utrecht, Netherlands. [Nijpels, Giel] Vrije Univ Amsterdam, Med Ctr, Dept Gen Practice, Inst Res Extramural Med,EMGO Inst, Amsterdam, Netherlands. [Stehouwer, Coen D. A.] Maastricht Univ, Med Ctr, Dept Internal Med, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. [Reijmer, Yael D.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Dekker, Jacqueline M.] Vrije Univ Amsterdam, Med Ctr, Inst Res Extramural Med, EMGO Inst, Amsterdam, Netherlands. RP Heringa, SM (reprint author), Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2014 VL 62 IS 5 BP 977 EP 979 DI 10.1111/jgs.12815 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AH8JY UT WOS:000336385300035 PM 24828928 ER PT J AU Zhu, CW Sano, M Ferris, SH Whitehouse, PJ Patterson, MB Galasko, D Schneider, LS Aisen, PS AF Zhu, Carolyn W. Sano, Mary Ferris, Steven H. Whitehouse, Peter J. Patterson, Marian B. Galasko, Douglas Schneider, Lon S. Aisen, Paul S. TI ALZHEIMER'S DISEASE COOPERATIVE STUDY PREVENTION INSTRUMENT PROJECT ASSESSING RESOURCE USE AND VOLUNTEER AND PAID WORK IN HEALTHY ELDERS: A LONGITUDINAL STUDY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID DEMENTIA C1 [Zhu, Carolyn W.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, Alzheimer Dis Res Ctr, New York, NY USA. [Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Ferris, Steven H.] NYU, Alzheimers Dis Ctr, Langone Med Ctr, New York, NY USA. [Whitehouse, Peter J.; Patterson, Marian B.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Galasko, Douglas; Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. RP Zhu, CW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. OI Ferris, Steven/0000-0001-8641-6223 FU NIA NIH HHS [P50 AG005142, U01AG10483, P50 AG005131, U01 AG010483, U19 AG010483, P50 AG005138, P30 AG008051] NR 7 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2014 VL 62 IS 5 BP 985 EP 988 DI 10.1111/jgs.12816 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AH8JY UT WOS:000336385300040 PM 24828933 ER PT J AU Aschenbrenner, M Ham, B Rauch, PK Sambolin, Z Silver, M Shockney, LD AF Aschenbrenner, Martha Ham, Bruce Rauch, Paula K. Sambolin, Zoraida Silver, Maya Shockney, Lillie D. TI NCCN Roundtable: Talking to Children About Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article AB A roundtable presentation at the NCCN 19th Annual Conference focused on the child's experience when a parent has cancer and concluded that honest communication, appropriate to the child's age and temperament, is essential, and that oncology providers should institute programs that help families deal with the illness. C1 [Shockney, Lillie D.] Johns Hopkins Breast Ctr, Baltimore, MD USA. [Aschenbrenner, Martha] Univ Texas MD Anderson Canc Ctr, Acute Palliat Care Inpatient Unit, Houston, TX 77030 USA. [Ham, Bruce] YMCA, Triangle Area North Carolina, Raleigh, NC 27605 USA. [Rauch, Paula K.] Massachusetts Gen Hosp, Ctr Canc, Marjorie E Korff PACT Program, Boston, MA USA. RP Aschenbrenner, M (reprint author), Univ Texas MD Anderson Canc Ctr, Acute Palliat Care Inpatient Unit, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2014 VL 12 IS 5.5 SI SI BP 777 EP 779 PG 3 WC Oncology SC Oncology GA AH9QF UT WOS:000336476200008 PM 24853215 ER PT J AU Anderson, K AF Anderson, Kenneth TI Multiple Myeloma: Advances Reported in 2013 Are Useful in the Clinic SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID LENALIDOMIDE AB Studies on multiple myeloma reported in 2013 offer support for maintenance after induction and consolidation in newly diagnosed patients eligible for transplantation and for continued lenalidomide in patients not eligible for transplantation. The newest available agents, carfilzomib and pomalidomide, are approved to treat relapsed/refractory myeloma, and in combination they produce impressive response rates and durability. On the horizon, new classes of agents promise even more impressive gains in remission and survival. C1 [Anderson, Kenneth] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Kenneth] LeBow Inst Myeloma Therapeut, Boston, MA USA. [Anderson, Kenneth] Dana Farber Brigham & Womens Canc Ctr, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. RP Anderson, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU OncoPep; Acetylon FX Dr. Anderson has disclosed that he has served as a scientific advisor for Celgene Corporation, Gilead, OncoPep, Onyx, and sanofi-aventis, and has received other financial benefit from OncoPep and Acetylon. NR 12 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2014 VL 12 IS 5.5 SI SI BP 808 EP 811 PG 4 WC Oncology SC Oncology GA AH9QF UT WOS:000336476200015 PM 24853222 ER PT J AU Gkotzamanidou, M Terpos, E Bamia, C Kyrtopoulos, SA Sfikakis, PP Dimopoulos, MA Souliotis, VL AF Gkotzamanidou, M. Terpos, E. Bamia, C. Kyrtopoulos, S. A. Sfikakis, P. P. Dimopoulos, M. A. Souliotis, V. L. TI Progressive changes in chromatin structure and DNA damage response signals in bone marrow and peripheral blood during myelomagenesis SO LEUKEMIA LA English DT Article DE myelomagenesis; epigenetics; DNA damage response signals; monoclonal gammopathy of undetermined significance; smoldering multiple myeloma; multiple myeloma ID SMOLDERING MULTIPLE-MYELOMA; STEM-CELL TRANSPLANTATION; GENE-EXPRESSION; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; CANCER; REPAIR; METHYLATION; MELPHALAN; P53 AB The molecular pathways implicated in multiple myeloma (MM) development are rather unknown. We studied epigenetic and DNA damage response (DDR) signals at selected model loci (N- ras, p53, d-globin) in bone marrow plasma cells and peripheral blood mononuclear cells (PBMCs) from patients with monoclonal gammopathy of undetermined significance (MGUS; n=20), smoldering/asymptomatic MM (SMM; n=29) and MM (n=18), as well as in healthy control-derived PBMCs (n=20). In both tissues analyzed, a progressive, significant increase in the looseness of local chromatin structure, gene expression levels and DNA repair efficiency from MGUS to SMM and finally to MM was observed (all P<0.002). Following ex vivo treatment with melphalan, a gradual suppression of the apoptotic pathway occurred in samples collected at different stages of myelomagenesis, with the severity and duration of the inhibition of RNA synthesis, p53 phosphorylation at serine15 and induction of apoptosis being higher in MGUS than SMM and lowest in MM patients (all P<0.0103). Interestingly, for all endpoints analyzed, a strong correlation between plasma cells and corresponding PBMCs was observed (all P<0.0003). We conclude that progressive changes in chromatin structure, transcriptional activity and DDR pathways during myelomagenesis occur in malignant plasma cells and that these changes are also reflected in PBMCs. C1 [Gkotzamanidou, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gkotzamanidou, M.; Terpos, E.; Dimopoulos, M. A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Bamia, C.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Kyrtopoulos, S. A.; Souliotis, V. L.] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, Athens 11635, Greece. [Sfikakis, P. P.] Sch Med, Dept Propedeut Med 1, Athens, Greece. RP Souliotis, VL (reprint author), Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, 48 Vassileos Constantinou Ave, Athens 11635, Greece. EM vls@eie.gr FU ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility) Network of Excellence of the European Union [513943] FX This work was partly supported by the ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility) Network of Excellence of the European Union (contract no. 513943). NR 49 TC 6 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAY PY 2014 VL 28 IS 5 BP 1113 EP 1121 DI 10.1038/leu.2013.284 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA AI2BJ UT WOS:000336661500015 PM 24089038 ER PT J AU Anderson, NM Harrold, I Mansour, MR Sanda, T McKeown, M Nagykary, N Bradner, JE Zhang, GL Look, AT Feng, H AF Anderson, N. M. Harrold, I. Mansour, M. R. Sanda, T. McKeown, M. Nagykary, N. Bradner, J. E. Zhang, G. Lan Look, A. T. Feng, H. TI BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more-differentiated T- ALL cell lines SO LEUKEMIA LA English DT Letter ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER; POTENT; FAMILY C1 [Anderson, N. M.; Harrold, I.; Nagykary, N.; Feng, H.] Boston Univ, Sch Med, Sect Hematol & Med Oncol, Dept Pharmacol & Expt Therapeut,Ctr Canc Res, Boston, MA 02118 USA. [Mansour, M. R.; Look, A. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mansour, M. R.] UCL, Univ Coll London Canc Inst, Dept Haematol, London, England. [Sanda, T.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [McKeown, M.; Bradner, J. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, G. Lan] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA. RP Anderson, NM (reprint author), Boston Univ, Sch Med, Sect Hematol & Med Oncol, Dept Pharmacol & Expt Therapeut,Ctr Canc Res, Boston, MA 02118 USA. EM Thomas_look@dfci.harvard.edu FU NCI NIH HHS [R00 CA134743, 1R01 CA176746, 4R00CA134743, P01 CA109901, R01 CA176746]; NHLBI NIH HHS [T32 HL007501, T32 HL7501] NR 12 TC 11 Z9 11 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAY PY 2014 VL 28 IS 5 BP 1145 EP 1148 DI 10.1038/leu.2013.377 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AI2BJ UT WOS:000336661500024 PM 24342948 ER PT J AU Goswami, M Hensel, N Smith, BD Prince, GT Qin, L Levitsky, HI Strickland, SA Jagasia, M Savani, BN Fraser, JW Sadrzadeh, H Rajkhowa, T Ito, S Jain, NA Battiwalla, M Fathi, AT Levis, MJ Barrett, AJ Hourigan, CS AF Goswami, M. Hensel, N. Smith, B. D. Prince, G. T. Qin, L. Levitsky, H. I. Strickland, S. A. Jagasia, M. Savani, B. N. Fraser, J. W. Sadrzadeh, H. Rajkhowa, T. Ito, S. Jain, N. A. Battiwalla, M. Fathi, A. T. Levis, M. J. Barrett, A. J. Hourigan, C. S. TI Expression of putative targets of immunotherapy in acute myeloid leukemia and healthy tissues SO LEUKEMIA LA English DT Letter ID CANCER-TESTIS ANTIGEN; CELLS; RESPONSES C1 [Goswami, M.; Hourigan, C. S.] NHLBI, Myeloid Malignancies Sect, NIH, Bethesda, MD 20892 USA. [Hensel, N.; Ito, S.; Jain, N. A.; Battiwalla, M.; Barrett, A. J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Smith, B. D.; Prince, G. T.; Qin, L.; Levitsky, H. I.; Rajkhowa, T.; Levis, M. J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Levitsky, H. I.] Roche Glycart AG, Canc Immunol Expt Med Pharma Res & Early Dev, Schlieren, Switzerland. [Strickland, S. A.; Jagasia, M.; Savani, B. N.] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. [Fraser, J. W.; Sadrzadeh, H.; Fathi, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Leukaemia, Boston, MA USA. [Fraser, J. W.; Sadrzadeh, H.; Fathi, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit,Div Hematol Oncol, Boston, MA USA. RP Goswami, M (reprint author), NHLBI, Myeloid Malignancies Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hourigan@nih.gov RI Hourigan, Christopher/S-2476-2016; OI Hourigan, Christopher/0000-0002-6189-8067; Strickland, Stephen/0000-0002-6861-2041 FU Intramural NIH HHS [ZIA HL006163-01]; NCATS NIH HHS [UL1 TR001079]; NCI NIH HHS [P01 CA015396] NR 15 TC 14 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAY PY 2014 VL 28 IS 5 BP 1167 EP 1170 DI 10.1038/leu.2014.14 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AI2BJ UT WOS:000336661500030 PM 24472813 ER PT J AU Harisinghani, MG AF Harisinghani, Mukesh G. TI The Male Pelvis Preface SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mharisinghani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 EI 1557-9786 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2014 VL 22 IS 2 BP XI EP XI DI 10.1016/j.mric.2014.02.001 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI1TC UT WOS:000336636700001 PM 24792681 ER PT J AU Sheth, RA Bittencourt, LK Guimaraes, AR AF Sheth, Rahul A. Bittencourt, Leonardo K. Guimaraes, Alexander R. TI Diffusion-Weighted Imaging of the Male Pelvis SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Diffusion-weighted imaging; Male pelvis; Magnetic resonance imaging; Cancer ID ADVANCED RECTAL-CANCER; NEOADJUVANT CHEMORADIATION THERAPY; RADICAL PROSTATECTOMY SPECIMENS; PATHOLOGICAL COMPLETE RESPONSE; SEMINAL-VESICLE INVASION; MAGNETIC-RESONANCE; RADIATION-THERAPY; BLADDER-CANCER; PREOPERATIVE CHEMORADIATION; COEFFICIENT VALUES AB Diffusion-weighted (DW) imaging is playing an increasingly important role in disease detection, prognostication, and monitoring of treatment response. Particularly in the realm of oncology, the potential applications for DW imaging continue to expand. In this article, the authors detail the role of DW imaging for pathologic processes involving the male pelvis. The authors describe the current data, new insights, and ongoing controversies regarding DW imaging of the male pelvis with a particular emphasis on oncologic applications. The authors also discuss imaging techniques and common pitfalls for DW imaging in this anatomic region. C1 [Sheth, Rahul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bittencourt, Leonardo K.] Univ Fed Rio de Janeiro, Dept Radiol, Clin Diagnost Imagem CDPI, BR-22640902 Rio De Janeiro, Brazil. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM aguimaraes@mgh.harvard.edu NR 82 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 EI 1557-9786 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2014 VL 22 IS 2 BP 145 EP + DI 10.1016/j.mric.2014.01.003 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI1TC UT WOS:000336636700005 PM 24792675 ER PT J AU Abtahi, SM Mao, Y Prapruttam, D Elmi, A Hedgire, SS AF Abtahi, Seyed Mahdi Mao, Yun Prapruttam, Duangkamon Elmi, Azadeh Hedgire, Sandeep S. TI Magnetic Resonance Imaging of Pelvic Metastases in Male Patients SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Pelvic metastases; MR imaging; Nodal metastases; Skeletal metastases; Peritoneal metastases ID SKELETAL-MUSCLE METASTASES; URINARY-BLADDER CANCER; LYMPH-NODE INVOLVEMENT; H-1 MR SPECTROSCOPY; PROSTATE-CANCER; TESTICULAR NEOPLASMS; RECTAL-CANCER; VERTEBRAL METASTASES; BONE-SCINTIGRAPHY; CARCINOMA AB Magnetic resonance (MR) imaging offers a noninvasive tool for diagnosis of primary and metastatic pelvic tumors. The diagnosis of a pelvic metastatic lesion implies an adverse prognosis and dictates the management strategies. Knowledge of normal MR imaging anatomy of the pelvis and the signal characteristics of normal and abnormal structures is essential for accurate interpretation of pelvic MR imaging. This article reviews imaging manifestations of nodal, visceral, and musculoskeletal metastatic lesions of the pelvis along with current and evolving MR imaging techniques. C1 [Abtahi, Seyed Mahdi; Mao, Yun; Prapruttam, Duangkamon; Elmi, Azadeh; Hedgire, Sandeep S.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Hedgire, SS (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM hedgire.sandeep@mgh.harvard.edu NR 90 TC 1 Z9 1 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 EI 1557-9786 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2014 VL 22 IS 2 BP 201 EP + DI 10.1016/j.mric.2014.01.006 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI1TC UT WOS:000336636700008 PM 24792678 ER PT J AU Motiejunaite, R Aranda, J Kazlauskas, A AF Motiejunaite, Ruta Aranda, Jorge Kazlauskas, Andrius TI Pericytes prevent regression of endothelial cell tubes by accelerating metabolism of lysophosphatidic acid SO MICROVASCULAR RESEARCH LA English DT Article ID BLOOD-VESSELS; VASCULAR DEVELOPMENT; SELECTIVE AGONIST; PHOSPHATASE LPP3; LPA(3) RECEPTOR; AUTOTAXIN; VEGF; ANGIOGENESIS; EXPRESSION; LYSOPHOSPHOLIPIDS AB Efforts to eradicate pathological vessels in neovascular diseases and induce growth of mature, functional vasculature in ischemic diseases are limited by our incomplete understanding of molecular mechanisms of vessel stabilization. While it is well known that pericytes stabilize blood vessels, the underlying mechanisms have not been fully elucidated. The goal of this study was to further investigate the mechanisms by which pericytes stabilize vessels. In an in vitro model of blood vessels, in which regression is driven by lysophosphatidic acid (LPA), pericyte-mediated stabilization was associated with a decrease in the concentration of LPA. The decline in the concentration of LPA was not caused by a reduction in activity or expression of autotaxin, the main enzyme implicated in LPA production. Rather, pericytes accelerated LPA metabolism. Stabilization of tubes by pericytes correlated with accelerated LPA dephosphorylation and increased expression of lipid phosphate phosphatases (LPPs). Finally, pericytes failed to stabilize tubes exposed to an LPA analogue, which was resistant to degradation. Our results suggest that pericytes stabilize endothelial cell tubes by accelerating the metabolism of LPA. (C) 2014 Elsevier Inc. All rights reserved. C1 [Motiejunaite, Ruta; Aranda, Jorge; Kazlauskas, Andrius] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Motiejunaite, Ruta] Vilnius Univ, Dept Biochem & Biophys, LT-03101 Vilnius, Lithuania. RP Kazlauskas, A (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu FU NIH [EY018344]; Lithuanian National Science Foundation FX We thank Dr. Andrew Morris (University of Kentucky) for mass spectrometry analysis and helpful discussions. We also thank Dr. Huib Ovaa (Netherlands Cancer Institute) for the gift of HA130, Drs. Timothy Clair and Mary Stracke (National Institutes of Health) for the ATX antibody, Dr. Kazuhiko Kume (Tokyo University) for the plasmid encoding LPA acyl transferase and Dr. George Davis (University of Missouri Columbia) for bovine retinal pericytes. VEGF-A used in this study was generously provided by the Biological Resources Branch Preclinical Repository at the National Cancer Institute. We thank Drs. Sarah Jacobo, Steven Pennock, and Guoxiang Ruan for critical reading of the manuscript. This work was supported by NIH grant EY018344 to A.K. R.M. received support from the Lithuanian National Science Foundation. NR 59 TC 8 Z9 10 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 EI 1095-9319 J9 MICROVASC RES JI Microvasc. Res. PD MAY PY 2014 VL 93 BP 62 EP 71 DI 10.1016/j.mvr.2014.03.003 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AI0TD UT WOS:000336562000011 PM 24681425 ER PT J AU Stricker, TP La Madrid, AM Chlenski, A Guerrero, L Salwen, HR Gosiengfiao, Y Perlman, EJ Furman, W Bahrami, A Shohet, JM Zage, PE Hicks, MJ Shimada, H Suganuma, R Park, JR So, S London, WB Pytel, P Maclean, KH Cohn, SL AF Stricker, Thomas P. La Madrid, Andres Morales Chlenski, Alexandre Guerrero, Lisa Salwen, Helen R. Gosiengfiao, Yasmin Perlman, Elizabeth J. Furman, Wayne Bahrami, Armita Shohet, Jason M. Zage, Peter E. Hicks, M. John Shimada, Hiroyuki Suganuma, Rie Park, Julie R. So, Sara London, Wendy B. Pytel, Peter Maclean, Kirsteen H. Cohn, Susan L. TI Validation of a prognostic multi-gene signature in high-risk neuroblastoma using the high throughput digital NanoString nCounter (TM) system SO MOLECULAR ONCOLOGY LA English DT Article DE High-risk neuroblastoma; Gene signature; Molecular classifier; NanoString; nCounter ID GENE-EXPRESSION; CLASSIFICATION; PREDICTION; THERAPY; SAMPLES; TRIAL; CHILDREN AB Microarray-based molecular signatures have not been widely integrated into neuroblastoma diagnostic classification systems due to the complexities of the assay and requirement for high-quality RNA. New digital technologies that accurately quantify gene expression using RNA isolated from formalin-fixed paraffin embedded (FFPE) tissues are now available. In this study, we describe the first use of a high-throughput digital system to assay the expression of genes in an "ultra-high risk" microarray classifier in FFPE high-risk neuroblastoma tumors. Customized probes corresponding to the 42 genes in a published multi-gene neuroblastoma signature were hybridized to RNA isolated from 107 FFPE high-risk neuroblastoma samples using the NanoString nCounter (TM) Analysis System. For classification of each patient, the Pearson's correlation coefficient was calculated between the standardized nCounter (TM) data and the molecular signature from the microarray data. We demonstrate that the nCounter (TM) 42-gene panel sub-stratified the high-risk cohort into two subsets with statistically significantly different overall survival (p = 0.0027) and event-free survival (p = 0.028). In contrast, none of the established prognostic risk markers (age, stage, tumor histology, MYCN status, and ploidy) were significantly associated with survival. We conclude that the nCounter (TM) System can reproducibly quantify expression levels of signature genes in FFPE tumor samples. Validation of this microarray signature in our high-risk patient cohort using a completely different technology emphasizes the prognostic relevance of this classifier. Prospective studies testing the prognostic value of molecular signatures in high-risk neuroblastoma patients using FFPE tumor samples and the nCounter (TM) System are warranted. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Stricker, Thomas P.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA. [La Madrid, Andres Morales; Chlenski, Alexandre; Guerrero, Lisa; Salwen, Helen R.; Cohn, Susan L.] Univ Chicago, Comer Childrens Hosp, Dept Pediat, Chicago, IL 60637 USA. [Gosiengfiao, Yasmin] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Perlman, Elizabeth J.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Furman, Wayne] St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. [Bahrami, Armita] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Shohet, Jason M.; Zage, Peter E.] Baylor Coll Med, Dept Pediat, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Hicks, M. John] Baylor Coll Med, Dept Pathol, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Shimada, Hiroyuki; Suganuma, Rie] Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. [Park, Julie R.; So, Sara] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Park, Julie R.; So, Sara] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [London, Wendy B.] Stat & Data Ctr, Childrens Oncol Grp, Boston, MA USA. [London, Wendy B.] Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Pytel, Peter] Univ Chicago, Comer Childrens Hosp, Dept Pathol, Chicago, IL 60637 USA. [Maclean, Kirsteen H.] NanoString Technol, Seattle, WA USA. RP Cohn, SL (reprint author), Univ Chicago, Comer Childrens Hosp, Dept Pediat, KCBD, Rm 5100,900 E 57th St, Chicago, IL 60637 USA. EM scohn@peds.bsd.uchicago.edu OI Gosiengfiao, Yasmin/0000-0002-8064-2462 FU Conquer Cancer Foundation; St. Baldrick's Foundation; Children's Neuroblastoma Cancer Foundation; Neuroblastoma Children's Cancer Society; Elise Anderson Foundation; National Cancer Institute [1K08CA148912] FX This work was supported by Conquer Cancer Foundation (AML); St. Baldrick's Foundation (AML); Children's Neuroblastoma Cancer Foundation (SLC); Neuroblastoma Children's Cancer Society (SLC); Elise Anderson Foundation (SLC), and The National Cancer Institute 1K08CA148912 (TPS). NR 31 TC 15 Z9 15 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD MAY PY 2014 VL 8 IS 3 BP 669 EP 678 DI 10.1016/j.molonc.2014.01.010 PG 10 WC Oncology SC Oncology GA AH9OQ UT WOS:000336472100019 PM 24560446 ER PT J AU Desai, RJ Hernandez-, S Bateman, BT Huybrechts, KF AF Desai, Rishi J. Hernandez-, Sonia Bateman, Brian T. Huybrechts, Krista F. TI Increase in Prescription Opioid Use During Pregnancy Among Medicaid-Enrolled Women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID UNITED-STATES; NONCANCER PAIN; TRENDS AB OBJECTIVE: To report the prevalence of prescription opioid use and evaluate the trends in a large cohort of Medicaid-enrolled pregnant women. METHODS: A cohort of pregnancies was identified using data from the Medicaid Analytical eXtract for the period of 2000-2007. Dispensing of opioids, as a class and separately for individual agents, was evaluated using claims from filled prescriptions. Variations in patterns of prescription opioid fills were examined by demographic characteristics, by geographic region, and over time. Median number of opioid prescriptions dispensed and cumulative days of availability for prescription opioids during pregnancy were reported. RESULTS: The study population consisted of more than 1.1 million women with completed pregnancies from 46 U. S. states and Washington, DC. One of five women from our cohort (21.6%) filled a prescription for an opioid during pregnancy; this proportion increased from 18.5% in 2000 to 22.8% in 2007. Substantial regional variation was seen with the proportion of women who filled a prescription during pregnancy, ranging between 9.5% and 41.6% across the states. Codeine and hydrocodone were the most commonly prescribed opioids. Among women filling at least one opioid prescription, the median (interquartile range) number of prescriptions filled was 1 (1-2) and the median (interquartile range) cumulative days of opioid availability during pregnancy were 5 (3-13) days. CONCLUSION: We observed high and increasing number of filled prescriptions for opioids during pregnancy among Medicaid-enrolled women. These findings call for further safety evaluations of these drugs and their effects on the developing fetus to inform clinical practice. C1 [Desai, Rishi J.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02120 USA. [Desai, Rishi J.] Harvard Univ, Sch Med, Boston, MA 02120 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02120 USA. Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02120 USA. RP Desai, RJ (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, 1620 Tremont St,Suite 3030-R, Boston, MA 02120 USA. EM rdesai2@partners.org FU K-award (from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [K08HD075831] FX Dr. Hernandez-Diaz has consulted for Novartis, AstraZeneca, and GSK_biologics for unrelated projects. Dr. Bateman is supported through a K-award (K08HD075831 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The other authors did not report any potential conflicts of interest. NR 16 TC 40 Z9 40 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2014 VL 123 IS 5 BP 997 EP 1002 DI 10.1097/AOG.0000000000000208 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BD UT WOS:000336809400014 PM 24785852 ER PT J AU Groah, SL Ljungberg, I Lichy, A Oyster, M Boninger, ML AF Groah, Suzanne L. Ljungberg, Inger Lichy, Alison Oyster, Michelle Boninger, Michael L. TI Disparities in Wheelchair Procurement by Payer Among People With Spinal Cord Injury SO PM&R LA English DT Article ID ELECTRIC-POWERED WHEELCHAIRS; MANUAL WHEELCHAIRS; ANSI/RESNA STANDARDS; PROPULSION; PARTICIPATION; BIOMECHANICS; DURABILITY; POSITION; COST AB Objective: To identify insurance provider-related disparities in the receipt of lightweight, customizable manual wheelchairs or power wheelchairs with programmable controls among community-dwelling people with spinal cord injury (SCI). Setting: Six Spinal Cord Injury Model System centers. Design: A multicenter cross-sectional study. Participants: A total of 359 individuals at least 16 years of age or older and 1 year after SCI who use a manual or power wheelchair as their. primary means of mobility. The subjects were stratified by payer, and payers were grouped according to reimbursement characteristics as follows: Medicaid/Department of Vocational Rehabilitation (DVR), private/prepaid, Medicare, Worker's Compensation (WC)/Veterans Affairs (VA), and self pay. Methods: Demographic, wheelchair, and payer data were collected by medical record review and face-to-face interview. Results: There were 125 participants in the Medicaid/DVR group, 120 in the private/ prepaid group, 55 in the Medicare group, 30 in the WC/VA group, and 29 in the self-pay group. For manual wheelchair users, the likelihood of having a lightweight, customizable wheelchair was 97.5% for private/prepaid, 96.3% for Medicaid/DVR, 94.1% for WC/VA, 87.5% for Medicare, and 82.6% for self pay. For power wheelchair users, those with WC/ VA (100%) were most likely to receive a customizable power wheelchair with programmable controls, followed by private/prepaid (95.1%), Medicaid/DVR (86.0 %), Medicare (83.9%), and self pay (50.0%). Conclusions: The only payer group for which all beneficiaries received wheelchairs that met standard of care were power wheelchairs provided by WC/VA. Fewer than 90% of people whose manual wheelchair was paid for by Medicare and self pay, and whose power wheelchair was paid for by Medicaid/DVR, Medicare, and self pay did not meet standard of care. Although these findings need to be correlated with long-term risks, such as overuse injuries, breakdowns, and participation, this study demonstrates that disparities in wheelchair procurement by insurance provider persist. C1 [Groah, Suzanne L.] Natl Rehabil Hosp, Washington, DC 20010 USA. [Ljungberg, Inger; Lichy, Alison] MedStar Natl Rehabil Hosp, Washington, DC USA. [Oyster, Michelle; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Oyster, Michelle; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Sch Med, Pittsburgh, PA USA. [Oyster, Michelle; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Associated Rehabil E, Pittsburgh, PA USA. RP Groah, SL (reprint author), Natl Rehabil Hosp, 102 Irving St, Washington, DC 20010 USA. EM suzanne.l.groah@medstar.net OI Boninger, Michael/0000-0001-6966-919X FU Department of Education/National Institute on Disability and Rehabilitation Research; National Institute on Disability and Rehabilitation Research FX grant, Department of Education/National Institute on Disability and Rehabilitation Research; Grant, National Institute on Disability and Rehabilitation Research NR 24 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAY PY 2014 VL 6 IS 5 BP 412 EP 417 DI 10.1016/j.pmrj.2013.11.004 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI0SR UT WOS:000336560700007 PM 24211695 ER PT J AU Furman, MB Plastaras, CT Popescu, A Tekmyster, G Davidoff, S Kennedy, DJ AF Furman, Michael B. Plastaras, Christopher T. Popescu, Adrian Tekmyster, Gene Davidoff, Scott Kennedy, David J. TI Should Antiplatelet Medications Be Held Before Cervical Epidural Injections? SO PM&R LA English DT Editorial Material ID THERAPY; DISCONTINUATION; CLOPIDOGREL; RISK; PAIN C1 [Furman, Michael B.] OSS Hlth, York, PA USA. [Plastaras, Christopher T.] Univ Penn, Dept Phys Med & Rehabil, Perelman Sch Med, Penn Spine Ctr, Philadelphia, PA 19104 USA. [Popescu, Adrian] Hosp Univ Penn, Philadelphia VA Med Ctr, Pain Med Div, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Tekmyster, Gene] Orthopaed & Sports Med Ctr, Trumbull, CT USA. [Davidoff, Scott] Main Line Spine, King Of Prussia, PA USA. [Kennedy, David J.] Stanford Univ, Dept Orthopaed, Redwood City, CA 94063 USA. RP Kennedy, DJ (reprint author), Stanford Univ, Dept Orthopaed, 450 Broadway St,MC 6342, Redwood City, CA 94063 USA. EM djkenned@stanford.edu NR 14 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAY PY 2014 VL 6 IS 5 BP 442 EP 445 DI 10.1016/j.pmrj.2014.04.012 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI0SR UT WOS:000336560700011 PM 24863733 ER PT J AU Furman, MB Plastaras, CT Popescu, A Tekmyster, G Davidoff, S Kennedy, DJ AF Furman, Michael B. Plastaras, Christopher T. Popescu, Adrian Tekmyster, Gene Davidoff, Scott Kennedy, David J. TI Should Antiplatelet Medications Be Held Before Cervical Epidural Injections? Response SO PM&R LA English DT Editorial Material ID TRANSFORAMINAL INJECTIONS; PERIOPERATIVE MANAGEMENT; CLOPIDOGREL THERAPY; PRACTICE GUIDELINES; EUROPEAN-SOCIETY; CARDIOLOGY ESC; TASK-FORCE; STENT; IMPLANTATION; DURATION C1 [Furman, Michael B.] OSS Hlth, York, PA USA. [Plastaras, Christopher T.] Univ Penn, Penn Spine Ctr, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Popescu, Adrian] Hosp Univ Penn, Philadelphia VA Med Ctr, Pain Med Div, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Tekmyster, Gene] Orthopaed & Sports Med Ctr, Trumbull, CT USA. [Davidoff, Scott] Main Line Spine, King Of Prussia, PA USA. [Kennedy, David J.] Stanford Univ, Dept Orthopaed, Redwood City, CA 94063 USA. RP Kennedy, DJ (reprint author), Stanford Univ, Dept Orthopaed, 450 Broadway St,MC 6342, Redwood City, CA 94063 USA. EM djkenned@stanford.edu NR 19 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAY PY 2014 VL 6 IS 5 BP 445 EP 447 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI0SR UT WOS:000336560700012 ER PT J AU Furman, MB Plastaras, CT Popescu, A Tekmyster, G Davidoff, S Kennedy, DJ AF Furman, Michael B. Plastaras, Christopher T. Popescu, Adrian Tekmyster, Gene Davidoff, Scott Kennedy, David J. TI Should Antiplatelet Medications Be Held Before Cervical Epidural Injections? SO PM&R LA English DT Editorial Material ID ANGIOGRAPHY C1 [Furman, Michael B.] OSS Hlth, York, PA USA. [Plastaras, Christopher T.] Univ Penn, Penn Spine Ctr, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Popescu, Adrian] Hosp Univ Penn, Dept Phys Med & Rehabil, Pain Med Div, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Tekmyster, Gene] Orthopaed & Sports Med Ctr, Trumbull, CT USA. [Davidoff, Scott] Main Line Spine, King Of Prussia, PA USA. [Kennedy, David J.] Stanford Univ, Dept Orthopaed, Redwood City, CA 94063 USA. RP Kennedy, DJ (reprint author), Stanford Univ, Dept Orthopaed, 450 Broadway St,MC 6342, Redwood City, CA 94063 USA. EM djkenned@stanford.edu NR 5 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAY PY 2014 VL 6 IS 5 BP 447 EP 448 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI0SR UT WOS:000336560700013 ER PT J AU Furman, MB Plastaras, CT Popescu, A Tekmyster, G Davidoff, S Kennedy, DJ AF Furman, Michael B. Plastaras, Christopher T. Popescu, Adrian Tekmyster, Gene Davidoff, Scott Kennedy, David J. TI Should Antiplatelet Medications Be Held Before Cervical Epidural Injections? SO PM&R LA English DT Editorial Material ID LONG-TERM DURATION; HEMATOMA; THERAPY; MANAGEMENT; TRIAL; PAIN C1 [Furman, Michael B.] OSS Hlth, York, PA USA. [Plastaras, Christopher T.] Univ Penn, Dept Phys Med & Rehabil, Perelman Sch Med, Penn Spine Ctr, Philadelphia, PA USA. [Popescu, Adrian] Hosp Univ Penn, Philadelphia VA Med Ctr, Pain Med Div, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Tekmyster, Gene] Orthopaed & Sports Med Ctr, Trumbull, CT USA. [Davidoff, Scott] Main Line Spine, King Of Prussia, PA USA. [Kennedy, David J.] Stanford Univ, Dept Orthopaed, Redwood City, CA 94063 USA. RP Kennedy, DJ (reprint author), Stanford Univ, Dept Orthopaed, 450 Broadway St,MC 6342, Redwood City, CA 94063 USA. EM djkenned@stanford.edu NR 13 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAY PY 2014 VL 6 IS 5 BP 448 EP 450 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI0SR UT WOS:000336560700014 ER PT J AU Samuelson, KW Koenig, CJ McCamish, N Choucroun, G Tarasovsky, G Bertenthal, D Seal, KH AF Samuelson, Kristin W. Koenig, Christopher J. McCamish, Nicole Choucroun, Gerard Tarasovsky, Gary Bertenthal, Daniel Seal, Karen H. TI Web-Based PTSD Training for Primary Care Providers: A Pilot Study SO PSYCHOLOGICAL SERVICES LA English DT Article DE posttraumatic stress disorder; primary care; veterans; Web-based ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; MENTAL-HEALTH DIAGNOSES; AFGHANISTAN VETERANS; FUNCTIONAL IMPAIRMENT; SURVEY REPLICATION; ANXIETY DISORDERS; IRAQ; SERVICES; BARRIERS AB Veterans with posttraumatic stress disorder (PTSD) symptoms frequently present to primary care providers (PCPs) and are reluctant to seek out or accept referrals to specialty mental health care. Most PCPs have not been trained to assess for and manage symptoms of PTSD. Web-based programs are increasingly used for medical education, but there are no published evaluations of online PTSD trainings for PCPs. We developed a 70-min Web-based training that focused on military-related PTSD for PCPs practicing in Veterans Affairs (VA) hospitals, but was applicable to PCPs treating veterans and other trauma-exposed patients outside VA settings. The training consisted of four modules: (1) Detection and Assessment; (2) Comorbid Conditions and Related Problems; (3) Pharmacological Interventions; and (4) Psychotherapeutic Interventions. Clinical vignettes dramatized key training concepts. Seventy-three PCPs completed the training and assessments pre- and posttraining and 30 days later. Paired t tests compared change in PTSD-related knowledge and comfort with PTSD-related skills, and qualitative methods were used to summarize participant feedback. After the training, mean knowledge score improved from 46% to 75% items correct, with sustained improvement at 30 days. Thirty days posttraining, PCPs reported significantly greater comfort regarding PTSD-related skills assessed; 47% reported using training content in their clinical practice. Qualitatively, PCPs appreciated the flexibility of asynchronous, self-paced online modules, but suggested more interactive content. Given the numerous barriers to specialty mental health treatment, coupled with a preference among veterans with PTSD for accessing treatment through primary care, improving PTSD competency among PCPs may help better serve veterans' mental health needs. C1 [Samuelson, Kristin W.] Alliant Int Univ, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94133 USA. [Samuelson, Kristin W.] Alliant Int Univ, Dept Mental Hlth, San Francisco, CA 94133 USA. [Samuelson, Kristin W.] Alliant Int Univ, Calif Sch Profess Psychol, San Francisco, CA 94133 USA. [Koenig, Christopher J.; McCamish, Nicole; Choucroun, Gerard; Tarasovsky, Gary; Bertenthal, Daniel; Seal, Karen H.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Koenig, Christopher J.; McCamish, Nicole; Choucroun, Gerard; Tarasovsky, Gary; Bertenthal, Daniel] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. [Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Samuelson, KW (reprint author), Alliant Int Univ, 1 Beach St,Suite 100, San Francisco, CA 94133 USA. EM ksamuelson@alliant.edu OI Koenig, Christopher J./0000-0003-0884-4120 NR 40 TC 0 Z9 0 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2014 VL 11 IS 2 BP 153 EP 161 DI 10.1037/a0034855 PG 9 WC Psychology, Clinical SC Psychology GA AI3TC UT WOS:000336784900004 PM 24364595 ER PT J AU Elbogen, EB Johnson, SC Newton, VM Timko, C Vasterling, JJ Van Male, LM Wagner, HR Beckham, JC AF Elbogen, Eric B. Johnson, Sally C. Newton, Virginia M. Timko, Christine Vasterling, Jennifer J. Van Male, Lynn M. Wagner, H. Ryan Beckham, Jean C. TI Protective Mechanisms and Prevention of Violence and Aggression in Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE violence; aggression; protective factors; veterans; rehabilitation ID POSTTRAUMATIC-STRESS-DISORDER; AFGHANISTAN WAR VETERANS; MENTAL-HEALTH PROBLEMS; COMBAT VETERANS; VIETNAM VETERANS; RISK-ASSESSMENT; MILITARY VETERANS; PSYCHOSOCIAL REHABILITATION; DECISION-MAKING; IRAQ AB Although a subset of Iraq and Afghanistan Veterans show aggression toward others after they return home from military service, little is known about protective mechanisms that could be bolstered to prevent violence. A national longitudinal survey was conducted between 2009 and 2011 using a random sample of veterans who served in Operation Iraqi Freedom or Operation Enduring Freedom. One thousand and ninety veterans, from 50 states representing all military branches, completed 2 waves of data collection, 1 year apart (retention rate = 79%). The final sample resembled the U.S. military post 9/11 in terms of age, sex, ethnicity, geography, and service branch. Protective mechanisms in socioeconomic (money to cover basic needs, stable employment), psychosocial (resilience, perceiving control over one's life, social support), and physical (healthy sleep, no physical pain) domains were examined. We found these protective mechanisms predicted decreased aggression and violence at follow-up, particularly among higher risk veterans. Multivariable analyses confirmed that protective mechanisms lowered violence through their interaction with risk factors. This study identifies protective mechanisms related to decreased community violence in veterans and indicates that rehabilitation aimed at improving socioeconomic, psychosocial, and physical well-being has potential promise to reduce aggression and violence among veterans after returning home from military service. C1 [Elbogen, Eric B.; Johnson, Sally C.; Newton, Virginia M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Elbogen, Eric B.; Wagner, H. Ryan; Beckham, Jean C.] Durham VA Med Ctr, Durham, NC USA. [Timko, Christine] VA Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, Hlth Serv Res & Dev Serv, Palo Alto, CA USA. [Timko, Christine] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Van Male, Lynn M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wagner, H. Ryan; Beckham, Jean C.] Midatlantic Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [Wagner, H. Ryan; Beckham, Jean C.] Duke Univ, Med Ctr, Durham, NC 27706 USA. RP Elbogen, EB (reprint author), Univ N Carolina, Chapel Hill Sch Med, Forens Psychiat Program & Clin, Dept Psychiat, CB 7167, Chapel Hill, NC 27599 USA. EM eric.elbogen@unc.edu FU NIMH NIH HHS [R01 MH080988, R01MH080988] NR 69 TC 3 Z9 3 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2014 VL 11 IS 2 BP 220 EP 228 DI 10.1037/a0035088 PG 9 WC Psychology, Clinical SC Psychology GA AI3TC UT WOS:000336784900012 PM 24512537 ER PT J AU Sherman, MD Kauth, MR Shipherd, JC Street, RL AF Sherman, Michelle D. Kauth, Michael R. Shipherd, Jillian C. Street, Richard L., Jr. TI Communication Between VA Providers and Sexual and Gender Minority Veterans: A Pilot Study SO PSYCHOLOGICAL SERVICES LA English DT Article DE veteran; sexual minority; gender minority; patient-provider communication; lesbian gay bisexual transgender ID HEALTH-CARE PROVIDERS; QUALITY-OF-CARE; TRANSGENDER VETERANS; GYNECOLOGIC CARE; HOMOSEXUAL-MEN; LESBIANS; WOMEN; ORIENTATION; EXPERIENCES; DISCLOSURE AB Approximately one million gay and lesbian Americans are veterans, and rates of engagement in the Veterans Affairs (VA) health care system may be increasing for both sexual and gender minority veterans. Very little research has examined the experience of these veterans when receiving care at VA health care facilities. The purpose of this study was to explore the experiences, beliefs, and preferences of lesbian, gay, bisexual, or transgender (LGBT) veterans in their communication with VA health care providers. LGBT veterans (n = 58) participated in focus groups or individual interviews and completed self-report measures at two southern VA hospitals. Approximately 2/3 of veterans report that none of their VA providers have specifically asked about their sexual orientation, and 24% of the veterans indicate that they have not disclosed their orientation to any VA provider. Although some veterans want providers to initiate these discussions, veterans also expressed fears about disclosure and its possible negative consequences. Similarly, LGBT veterans report varied opinions about the appropriateness of routine assessment of minority status. Only 28% of these veterans experience VA as welcoming to them as LGBT veterans. Systematic training is needed for all VA providers about the rationale for assessing sexual and gender orientation. Staff education should include specific skills for initiating these assessments, and ways of responding to veteran concerns about discussing this topic in the VA health care system. C1 [Sherman, Michelle D.] Oklahoma City VA Med Ctr, Oklahoma City, OK USA. [Sherman, Michelle D.] Oklahoma South Cent Mental Illness Res Educ & Cli, Oklahoma City, OK USA. [Kauth, Michael R.] Michael E DeBakey VA Med Ctr, South Cent Mental Illness Res Educ & Clin Ctr MIR, Houston, TX USA. [Kauth, Michael R.] VA Hlth Serv Res & Dev Houston Ctr Excellence, Houston, TX USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, Houston, TX USA. [Street, Richard L., Jr.] VA Hlth Serv Res & Dev Houston Ctr Innovat Qual E, Houston, TX USA. RP Sherman, MD (reprint author), 921 NE 13th St,116A, Oklahoma City, OK 73104 USA. EM michelle-sherman@ouhsc.edu NR 51 TC 18 Z9 18 U1 3 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD MAY PY 2014 VL 11 IS 2 BP 235 EP 242 DI 10.1037/a0035840 PG 8 WC Psychology, Clinical SC Psychology GA AI3TC UT WOS:000336784900014 PM 24588107 ER PT J AU Watanabe, H Brooks, AN Meyerson, M AF Watanabe, Hideo Brooks, Angela N. Meyerson, Matthew TI Breaking Down RET Breakpoints in Lung Adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID THYROID CARCINOMAS; GENE FUSIONS; CANCER; IDENTIFICATION; LEUKEMIA; TRANSLOCATION; ALK; GENERATION; RADIATION; ONCOGENE C1 [Watanabe, Hideo; Brooks, Angela N.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Watanabe, Hideo; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Watanabe, Hideo; Brooks, Angela N.; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu FU NCI NIH HHS [R01 CA109038, P01 CA154303]; NIA NIH HHS [P01 AG039355] NR 23 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2014 VL 9 IS 5 BP 590 EP 592 DI 10.1097/JTO.0000000000000168 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AF3QQ UT WOS:000334627500003 PM 24722148 ER PT J AU Gaspari, RJ Blehar, D Polan, D Montoya, A Alsulaibikh, A Liteplo, A AF Gaspari, Romolo J. Blehar, David Polan, David Montoya, Anthony Alsulaibikh, Amal Liteplo, Andrew TI The Massachusetts Abscess Rule: A Clinical Decision Rule Using Ultrasound to Identify Methicillin-resistant Staphylococcus aureus in Skin Abscesses SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID SOFT-TISSUE INFECTIONS; RISK-FACTORS; SONOGRAPHY; CELLULITIS; VALIDATION; DIAGNOSIS; TRENDS; MRSA AB ObjectivesTreatment failure rates for incision and drainage (I&D) of skin abscesses have increased in recent years and may be attributable to an increased prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Previous authors have described sonographic features of abscesses, such as the presence of interstitial fluid, characteristics of abscess debris, and depth of abscess cavity. It is possible that the sonographic features are associated with MRSA and can be used to predict the presence of MRSA. The authors describe a potential clinical decision rule (CDR) using sonographic images to predict the presence of CA-MRSA. MethodsThis was a pilot CDR derivation study using databases from two emergency departments (EDs) of patients presenting to the ED with uncomplicated skin abscesses who underwent I&D and culture of the abscess contents. Patients underwent ultrasound (US) imaging of the abscesses prior to I&D. Abscess contents were sent for culture and sensitivity. Two independent physicians experienced in soft tissue US blinded to the culture results and clinical data reviewed the images in a standardized fashion for the presence or absence of the predetermined image characteristics. In the instance of a disagreement between the initial two investigators, a third reviewer adjudicated the findings prior to analysis. The association between the primary outcome (presence of MRSA) and each sonographic feature was assessed using univariate and multivariate analysis. The reliability of each sonographic feature was measured by calculating the kappa () coefficient of interobserver agreement. The decision tree model for the CDR was created with recursive partitioning using variables that were both reliable and strongly associated with MRSA. ResultsOf the total of 2,167 patients who presented with skin and soft tissue infections during the study period, 605 patients met inclusion criteria with US imaging and culture and sensitivity of purulence. Among the pathogenic organisms, MRSA was the most frequently isolated, representing 50.1% of all patients. Six of the sonographic features were associated with the presence of MRSA, but only four of these features were reliable using the kappa analysis. Recursive partitioning identified three independent variables that were both associated with MRSA and reliable: 1) the lack of a well-defined edge, 2) small volume, and 3) irregular or indistinct shape. This decision rule demonstrates a sensitivity of 89.2% (95% confidence interval [CI] = 84.7% to 92.7%), a specificity of 44.7% (95% CI = 40.9% to 47.8%), a positive predictive value of 57.9 (95% CI = 55.0 to 60.2), a negative predictive value of 82.9 (95% CI = 75.9 to 88.5), and an odds ratio (OR) of 7.0 (95% CI = 4.0 to 12.2). ConclusionsAccording to our putative CDR, patients with skin abscesses that are small, irregularly shaped, or indistinct, with ill-defined edges, are seven times more likely to demonstrate MRSA on culture. Resumen ObjetivosLos porcentajes de fracaso terapeutico para la incision y el drenaje (IyD) de los abscesos cutaneos se han incrementado en los ultimos anos y puede ser atribuible a una prevalencia creciente de Staphylococcus aureus meticilin-resistente adquirido en la comunidad (SARM-AC). Algunos autores han descrito hallazgos ecograficos de los abscesos, como la presencia de liquido intersticial, las caracteristicas de los detritus del absceso y la profundidad de la cavidad del absceso. Es posible que los hallazgos ecograficos se asocien con SARM y puedan ser usados para predecir la presencia de SARM. Los autores describen un potencial regla de decision clinica (RDC) que usa imagenes ecograficas para predecir la presencia de SARM-AC. MetodologiaEstudio piloto de derivacion de una RDC que utilizo las bases de pacientes que acudieron a dos servicios de urgencias (SU) por un absceso cutaneo no complicado y en los que se llevo a cabo IyD y cultivo de los contenidos del absceso. A los pacientes se les realizo una ecografia de partes blandas previamente a la IyD. Los contenidos del absceso se enviaron para cultivo y antibiograma. Dos medicos independientes con experiencia en ecografia de partes blandas, ciegos a los resultados del cultivo y a los datos clinicos, revisaron las imagenes de una manera estandarizada para comprobar la presencia o la ausencia de los hallazgos de la imagen predeterminada. En caso de desacuerdo entre los investigadores, un tercer revisor asigno los hallazgos previamente al analisis. La asociacion entre el resultado principal (presencia de SARM) y cada hallazgo ecografico se evaluo mediante un analisis univariado y multivariado. La fiabilidad de cada hallazgo ecografico se midio calculando el coeficiente kappa (k) de concordancia interobservador. Se creo un modelo de arbol de decision para la RDC con particion recursiva usando variables que fueron tanto fiables como fuertemente asociadas con el SARM. ResultadosDel total de 2.167 pacientes que acudieron por una infeccion de piel y partes blandas durante el periodo del estudio, 605 cumplieron los criterios de inclusion con imagenes ecograficas y cultivo y antibiograma del exudado. Entre los organismos patogenos, SARM fue el mas frecuentemente aislado, y represento un 50,1% de todos los pacientes. Seis de los hallazgos ecograficos se asociaron con la presencia de SARM, pero solo cuatro fueron fiables mediante el analisis kappa. La particion recursiva identifico tres variables independientes que fueron fiables y asociadas con la presencia de SARM: 1) la falta de borde bien definido; 2) el volumen pequeno; y 3) la forma irregular o indeterminada. Esta regla de decision demuestra una sensibilidad del 89% (IC 95% = 85% a 93%), una especificidad del 45% (IC 95% = 41% a 48%), un valor predictivo positivo del 57,9% (IC 95% = 55,0 a 60,2), un valor predictivo negativo del 82,9% (IC 95% = 75,9% a 88,5%), y una razon de ventajas de 7,0 (IC 95% = 4,0 a 12,2). ConclusionesConforme a nuestra supuesta RDC, los pacientes con un absceso cutaneo que es pequeno, de forma irregular o indeterminada y con borde poco definido tienen una probabilidad 7 veces mayor de que se identifique SARM en el cultivo. C1 [Gaspari, Romolo J.; Blehar, David; Montoya, Anthony] UMass Mem Med Ctr, Dept Emergency Med, Worcester, MA 01605 USA. [Alsulaibikh, Amal; Liteplo, Andrew] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Gaspari, RJ (reprint author), UMass Mem Med Ctr, Dept Emergency Med, Worcester, MA 01605 USA. EM Romolo.Gaspari@umassmemorial.org RI Gaspari, Romolo/I-4649-2014; alsulaibikh, amal/F-9145-2015 OI Gaspari, Romolo/0000-0002-8411-0308; NR 26 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2014 VL 21 IS 5 BP 558 EP 567 DI 10.1111/acem.12379 PG 10 WC Emergency Medicine SC Emergency Medicine GA AH6VI UT WOS:000336269600011 PM 24842508 ER PT J AU Wu, H Wang, WC Liu, FY Weisberg, EL Tian, B Chen, YF Li, BH Wang, AL Wang, BL Zhao, Z McMillin, DW Hu, C Li, H Wang, JH Liang, YK Buhrlage, SJ Liang, JT Liu, J Yang, G Brown, JR Treon, SP Mitsiades, CS Griffin, JD Liu, QS Gray, NS AF Wu, Hong Wang, Wenchao Liu, Feiyang Weisberg, Ellen L. Tian, Bei Chen, Yongfei Li, Binhua Wang, Aoli Wang, Beilei Zhao, Zheng McMillin, Douglas W. Hu, Chen Li, Hong Wang, Jinhua Liang, Yanke Buhrlage, Sara J. Liang, Junting Liu, Jing Yang, Guang Brown, Jennifer R. Treon, Steven P. Mitsiades, Constantine S. Griffin, James D. Liu, Qingsong Gray, Nathanael S. TI Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma SO ACS CHEMICAL BIOLOGY LA English DT Article ID BRUTONS TYROSINE KINASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; TEC FAMILY KINASES; IRREVERSIBLE INHIBITORS; GENE REARRANGEMENT; TARGETING BTK; IBRUTINIB; PROTEIN; DOMAIN; DIFFERENTIATION AB BTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling and cellular assays to develop a potent, selective, and irreversible BTK kinase inhibitor, QL47, which covalently modifies Cys481. QL47 inhibits BTK kinase activity with an IC50 of 7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with an EC50 of 475 nM, and inhibits phosphorylation of a downstream effector PLC gamma 2 (Tyr759) with an EC50 of 318 nM. In Ramos cells QL47 induces a Cl cell cycle arrest that is associated with pronounced degradation of BTK protein. QL47 inhibits the proliferation of B-cell lymphoma cancer cell lines at submicromolar concentrations. C1 [Wu, Hong; Wang, Wenchao; Liu, Feiyang; Chen, Yongfei; Li, Binhua; Wang, Aoli; Wang, Beilei; Zhao, Zheng; Hu, Chen; Li, Hong; Liu, Jing; Liu, Qingsong] Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China. [Wu, Hong; Liu, Feiyang; Liu, Qingsong] Univ Sci & Technol China, Hefei 230036, Anhui, Peoples R China. [Weisberg, Ellen L.; McMillin, Douglas W.; Yang, Guang; Brown, Jennifer R.; Treon, Steven P.; Mitsiades, Constantine S.; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tian, Bei] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing 100730, Peoples R China. [Tian, Bei] Beijing Ophthalmol & Visual Sci Key Lab, Beijing 100730, Peoples R China. [Wang, Jinhua; Liang, Yanke; Buhrlage, Sara J.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liang, Junting] Chinese Acad Sci, Hefei Inst Phys Sci, Key Lab Ion Beam Bioengn, Hefei 230031, Anhui, Peoples R China. [Yang, Guang; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Liu, QS (reprint author), Chinese Acad Sci, High Field Magnet Lab, Mailbox 1110,350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China. EM Qsliu97@hmfl.ac.cn; nathanael_gray@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU Chinese Academy of Sciences; LINCS center [U54 HG006097] FX We are thankful for a Chinese Academy of Sciences training grant for support of H.W. and F.L. We also want to thank LINCS center U54 HG006097 (N.S.G.). NR 33 TC 12 Z9 13 U1 6 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD MAY PY 2014 VL 9 IS 5 BP 1086 EP 1091 DI 10.1021/cb4008524 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH5VO UT WOS:000336199400003 PM 24556163 ER PT J AU Kloverpris, HN Adland, E Koyanagi, M Stryhn, A Harndahl, M Matthews, PC Shapiro, R Walker, BD Ndung'u, T Brander, C Takiguchi, M Buus, S Goulder, P AF Kloverpris, Henrik N. Adland, Emily Koyanagi, Madoka Stryhn, Anette Harndahl, Mikkel Matthews, Philippa C. Shapiro, Roger Walker, Bruce D. Ndung'u, Thumbi Brander, Christian Takiguchi, Masafumi Buus, Soren Goulder, Philip TI HIV Subtype Influences HLA- B*07: 02-Associated HIV Disease Outcome SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; CLASS-I; IMMUNE CONTROL; ESCAPE PATHWAYS; CELL RESPONSES; GAG EPITOPE; VIRAL LOAD; INFECTION; TYPE-1 AB Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag GL9 (Gag355-363, GPSHKARVL) epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed. C1 [Kloverpris, Henrik N.; Adland, Emily; Matthews, Philippa C.; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. [Kloverpris, Henrik N.; Stryhn, Anette; Harndahl, Mikkel; Buus, Soren] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [Kloverpris, Henrik N.; Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Sch Med, K RITH, Durban, South Africa. [Koyanagi, Madoka; Takiguchi, Masafumi] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan. [Shapiro, Roger] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa. [Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, Irsicaixa AIDS Res Inst HIVACAT, Badalona, Spain. [Brander, Christian] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain. RP Kloverpris, HN (reprint author), Univ Kwazulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Sch Med, K RITH, 719 Umbilo Rd, ZA-4001 Durban, South Africa. EM henrik.kloverpris@k-rith.org RI Buus, Soren/F-5446-2010; Takiguchi, Masafumi/E-7468-2013; OI Buus, Soren/0000-0001-8363-1999; Brander, Christian/0000-0002-0548-5778; Ndung'u, Thumbi/0000-0003-2962-3992 FU Welcome Trust; National Institutes of Health [R01 AI46995]; Danish Agency for Science, Technology and Innovation [12-132295] FX This work was supported by the Welcome Trust (P.G.) and the National Institutes of Health, grant R01 AI46995. H.N.K holds a grant from the Danish Agency for Science, Technology and Innovation #12-132295. NR 41 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 2014 VL 30 IS 5 BP 468 EP 475 DI 10.1089/aid.2013.0197 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AG8IL UT WOS:000335661900010 PM 24010680 ER PT J AU Mendez, MF Fong, SS Shapira, JS Jimenez, EE Kaiser, NC Kremen, SA Tsai, PH AF Mendez, Mario F. Fong, Sylvia S. Shapira, Jill S. Jimenez, Elvira E. Kaiser, Natalie C. Kremen, Sarah A. Tsai, Po-Heng TI Observation of Social Behavior in Frontotemporal Dementia SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE dementia; frontotemporal lobar degeneration; Alzheimer's disease; social behavior; autism ID LOBAR DEGENERATION; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; MIND DEFICITS; RATING-SCALE; VARIANT; COGNITION; CONSENSUS AB Background: The most characteristic manifestations of behavioral variant frontotemporal dementia (bvFTD) are abnormalities in social behavior. However, distinguishing bvFTD based on social behavior can be difficult in structured clinical settings. Methods: Using a Social Observation Inventory, 10 patients with bvFTD and 10 patients with Alzheimer's disease (AD) were compared to their caregiver interlocutors on 1-hour mealtime, in-home videotaped segments. Results: Compared to caregivers and patients with AD, patients with bvFTD were significantly disturbed in social behavior. In contrast, patients with AD were indistinguishable from their caregivers. The lack of you comments and decreased tact and manners distinguished 92.6% of the patients with bvFTD from patients with AD and caregivers. The Social Observation Inventory scores correlated with scores on frontal-executive tests and socioemotional scales. Conclusions: The systematic observation of social behavior during routine activities may be one of the best ways to distinguish patients with bvFTD from normal individuals and from patients with other dementias. C1 [Mendez, Mario F.; Fong, Sylvia S.; Shapira, Jill S.; Jimenez, Elvira E.; Kaiser, Natalie C.; Kremen, Sarah A.; Tsai, Po-Heng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Fong, Sylvia S.; Shapira, Jill S.; Jimenez, Elvira E.; Kaiser, Natalie C.; Tsai, Po-Heng] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU NIH [R01AG034499-03] FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by NIH grant #R01AG034499-03. NR 37 TC 13 Z9 13 U1 2 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD MAY PY 2014 VL 29 IS 3 BP 215 EP 221 DI 10.1177/1533317513517035 PG 7 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA AI0HL UT WOS:000336527000005 PM 24370617 ER PT J AU Foley, JM Salat, DH Stricker, NH Zink, TA Grande, LJ McGlinchey, RE Milberg, WP Leritz, EC AF Foley, Jessica M. Salat, David H. Stricker, Nikki H. Zink, Tyler A. Grande, Laura J. McGlinchey, Regina E. Milberg, William P. Leritz, Elizabeth C. TI Interactive Effects of Apolipoprotein E4 and Diabetes Risk on Later Myelinating White Matter Regions in Neurologically Healthy Older Aged Adults SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Review DE Alzheimer's disease; diabetes; APOE4; healthy aging; white matter ID E EPSILON-4 ALLELE; MILD-COGNITIVE-IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; MEDIAL TEMPORAL-LOBE; ALZHEIMERS-DISEASE; DIFFUSION-TENSOR; MAGNETIC-RESONANCE; E GENOTYPE; AFRICAN-AMERICANS; APOE EPSILON-4 AB Possession of the apolipoprotein E4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI). Data were prepared using Tract-Based Spatial Statistics, and a priori regions of interest (ROIs) were extracted from T1-based WM parcellations. Regions of interest included later myelinating frontal/temporal/parietal WM regions and control regions measured by fractional anisotropy (FA). There were no APOE group differences in DTI for any ROI. Within the APOE4 group, we found negative relationships between hemoglobin A(1c)/fasting glucose and APOE4 on FA for all later myelinating WM regions but not for early/middle myelinating control regions. Results also showed APOE4/diabetes risk interactions for WM underlying supramarginal, superior temporal, precuneus, superior parietal, and superior frontal regions. Results suggest interactive effects of APOE4 and diabetes risk on later myelinating WM regions, which supports preclinical detection of AD among this particularly susceptible subgroup. C1 [Foley, Jessica M.; Salat, David H.; Stricker, Nikki H.; Zink, Tyler A.; Grande, Laura J.; McGlinchey, Regina E.; Milberg, William P.; Leritz, Elizabeth C.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Foley, Jessica M.; Salat, David H.; Zink, Tyler A.; Grande, Laura J.; McGlinchey, Regina E.; Milberg, William P.; Leritz, Elizabeth C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Salat, David H.; Leritz, Elizabeth C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Stricker, Nikki H.; Zink, Tyler A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Leritz, Elizabeth C.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Foley, JM (reprint author), VA Boston Med Ctr 116B, 150S Huntington Ave, Jamaica Plain, MA 02130 USA. EM jfoley@post.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU National Institute of Neurologic Disorders and Stroke [K23NS062148]; National Institute of Nursing Research [R01NR010827]; National Institute on Aging [P60AG08812, P01AG004390]; American Psychological Association Division [40]; The Rosalind and Arthur Gilbert Foundation/AFAR New Investigator Award in Alzheimer's Disease; Medical Research Service VA Merit Review Awards FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Neurologic Disorders and Stroke (K23NS062148), the National Institute of Nursing Research (R01NR010827), the National Institute on Aging (P60AG08812 and P01AG004390), American Psychological Association Division 40, The Rosalind and Arthur Gilbert Foundation/AFAR New Investigator Award in Alzheimer's Disease, and by Medical Research Service VA Merit Review Awards to William Milberg and Regina McGlinchey. NR 111 TC 4 Z9 4 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD MAY PY 2014 VL 29 IS 3 BP 222 EP 235 DI 10.1177/1533317513517045 PG 14 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA AI0HL UT WOS:000336527000006 PM 24381137 ER PT J AU Kasckow, J Golshan, S Zisook, S AF Kasckow, John Golshan, Shahrokh Zisook, Sidney TI Does Age Moderate the Relationship Between Depressive Symptoms and Suicidal Ideation in Middle-Aged and Older Patients with Schizophrenia and Subthreshold Depression? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Age; depression; moderation; schizophrenia; suicidal ideation ID RATING-SCALE AB Background: Suicidal deaths in middle-aged and older individuals with schizophrenia are a public health concern. Depression and schizophrenia are major risk factors for suicide. However, it is unknown whether age moderates the relationship between depression and suicidal ideation in patients with schizophrenia and subthreshold depression. Methods: Suicidal ideation was assessed with the InterSePT Scale for Suicidal Ideation and the Clinical Global Impression-Suicide Severity Scale in outpatients older than 39 years with schizophrenia and subthreshold depression (n = 213). Using linear regression, we examined whether depression (based on Calgary Depression Rating Scale scores), age, and "age by depressive symptoms" predicted suicidal ideation. Results: Depressive symptoms predicted suicidal ideation. Neither age nor "depressive symptoms by age" predicted suicidal ideation. Conclusions: In this population, age does not appear to moderate the relationship between depressive symptoms and suicidal behavior. Thus, assessing depressive symptoms as a risk factor is important at all ages in this population. C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, MIRECC, Pittsburgh, PA 15240 USA. [Kasckow, John] Univ Pittsburgh, Med Ctr, Behav Hlth Serv, Pittsburgh, PA USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Golshan, Shahrokh; Zisook, Sidney] VA San Diego Hlth Care Syst, San Diego, CA USA. [Golshan, Shahrokh; Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Kasckow, J (reprint author), VA Pittsburgh Hlth Care Syst, Behav Hlth, Univ Dr, Pittsburgh, PA 15240 USA. EM kasckowjw@upmc.edu FU VA HSRD [PPO 10-249-2]; VISN [4, 22 MIRECC]; University of California, San Diego Center for Community-Based Research in Older People with Psychoses; Cincinnati VAMC; University of Cincinnati College of Medicine; PamLab; Astra Zeneca; [MH6398] FX This work was supported by MH6398 (SZ and JK), VA HSRD PPO 10-249-2 (JK), the VISN 4 and VISN 22 MIRECC, and the University of California, San Diego Center for Community-Based Research in Older People with Psychoses. The authors thank the Cincinnati VAMC and the University of Cincinnati College of Medicine for support. The contents of this article do not represent the views of the US government or the Department of Veterans Affairs of the US government. SZ has received research support from PamLab, and JK has received research support from Astra Zeneca. NR 10 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAY PY 2014 VL 22 IS 5 BP 437 EP 441 DI 10.1016/j.jagp.2013.01.039 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH4HE UT WOS:000336087200003 PM 23567374 ER PT J AU Harper, DG Jensen, JE Ravichandran, C Sivrioglu, Y Silveri, M Iosifescu, DV Renshaw, PF Forester, BP AF Harper, David G. Jensen, J. Eric Ravichandran, Caitlin Sivrioglu, Yusuf Silveri, Marisa Iosifescu, Dan V. Renshaw, Perry F. Forester, Brent P. TI Tissue-Specific Differences in Brain Phosphodiesters in Late-Life Major Depression SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE MRSI; P-31 MRS; elderly; aging; membranes ID MAGNETIC-RESONANCE-SPECTROSCOPY; INDEPENDENT PHOSPHOLIPASE A(2); WHITE-MATTER LESIONS; PHOSPHATIDYLCHOLINE METABOLISM; EXECUTIVE DYSFUNCTION; VASCULAR DEPRESSION; CULTURED-CELLS; FRONTAL-LOBE; 4 TESLA; PHOSPHATIDYLETHANOLAMINE AB Objective: Late-life depression has been hypothesized to have a neurodegenerative component that leads to impaired executive function and increases in subcortical white matter hyperintensities. Phosphorus magnetic resonance spectroscopy (MRS) can quantify several important phosphorus metabolites in the brain, particularly the anabolic precursors and catabolic metabolites of the constituents of cell membranes, which could be altered by neurodegenerative activity. Methods: Ten patients with late-life major depression who were medication free at time of study and 11 aged normal comparison subjects were studied using P-31 MRS three-dimensional chemical shift imaging at 4 Tesla. Phosphatidylcholine and phosphatidylethanolamine comprise 90% of cell membranes in brain but cannot be quantified precisely with 31P MRS. We measured phosphocholine and phosphoethanolamine, which are anabolic precursors, as well as glycerophosphocholine and glycerophosphoethanolamine, which are catabolic metabolites of phosphatidylcholine and phosphatidylethanolamine. Results: In accordance with our hypotheses, glycerophosphoethanolamine was elevated in white matter of depressed subjects, suggesting enhanced breakdown of cell membranes in these subjects. Glycerophosphocholine did not show any significant difference between comparison and depressed subjects but both showed an enhancement in white matter compared with gray matter. Contrary to our hypotheses, neither phosphocholine nor phosphoethanolamine showed evidence for reduction in late-life depression. Conclusion: These findings support the hypothesis that neurodegenerative processes occur in white matter in patients with late-life depression more than in the normal elderly population. C1 [Harper, David G.; Forester, Brent P.] McLean Hosp, Geriatr Psychiat Program, Belmont, MA 02478 USA. [Jensen, J. Eric; Silveri, Marisa] McLean Hosp, Neuroimaging Ctr, Belmont, MA 02478 USA. [Ravichandran, Caitlin] McLean Hosp, Lab Psychiat Biostat, Belmont, MA 02478 USA. [Harper, David G.; Jensen, J. Eric; Ravichandran, Caitlin; Silveri, Marisa; Iosifescu, Dan V.; Forester, Brent P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sivrioglu, Yusuf] Uludag Univ, Fac Med, Dept Psychiat, Bursa, Turkey. [Iosifescu, Dan V.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT USA. RP Harper, DG (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM dharper@mclean.harvard.edu FU Rogers' Family Foundation; National Association for Research on Schizophrenia and Affective Disease (NARSAD); Pfizer [K23 MH07728, R01 MH058681, R01 DA015116, R01 AG20654]; Harvard Catalyst; Janssen; Eli Lilly; Organon; NARSAD; NIA; GSK; Roche; Pfizer, Inc.; Glaxo Smith Kline; National Institute of Mental Health; Aspect Medical Systems; Forest Laboratories; Janssen Pharmaceutica FX This study was funded by The Rogers' Family Foundation, National Association for Research on Schizophrenia and Affective Disease (NARSAD), Pfizer, K23 MH07728, R01 MH058681, R01 DA015116, R01 AG20654, and Harvard Catalyst.; The authors have no competing financial interests to disclose. Dr. Harper receives grant support from Janssen, Eli Lilly, The Rogers' Family Foundation, Organon, NARSAD, and NIA. Dr. Renshaw reports that he is a consultant for Novartis, Ridge Diagnostics, and Kyowa Hakko. He receives research support from GSK and Roche. Dr. Forester reports work with Speaker's Bureaus for Eli Lilly, Novartis, and Astra Zeneca, all of which ended on September 1, 2010. He served on a Data Safety Management Board for Repligen ending January 2010, and has grant support from Pfizer, Inc., Glaxo Smith Kline, NARSAD, Rogers' Family Foundation, and National Institute of Mental Health. In the past 3 years, Dr. Iosifescu has received research support from Aspect Medical Systems, Forest Laboratories, and Janssen Pharmaceutica; he has received speaker honoraria from Eli Lilly & Co., Pfizer, Inc., and Reed Elsevier Medical. Dr. Silveri, Dr. Sivrioglu, and Dr. Jensen report no conflicts. NR 51 TC 11 Z9 11 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAY PY 2014 VL 22 IS 5 BP 499 EP 509 DI 10.1016/j.jagp.2012.08.005 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH4HE UT WOS:000336087200010 PM 23567437 ER PT J AU Mull, HJ Borzecki, AM Chen, Q Shin, MH Rosen, AK AF Mull, Hillary J. Borzecki, Ann M. Chen, Qi Shin, Marlena H. Rosen, Amy K. TI Using AHRQ Patient Safety Indicators to Detect Postdischarge Adverse Events in the Veterans Health Administration SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE PSI; Veterans Health Administration; administrative data; patient safety; adverse event ID POSITIVE PREDICTIVE-VALUE; POSTOPERATIVE HEMORRHAGE; READMISSIONS; HEMATOMA; VALIDITY; QUALITY; IMPACT; CARE AB Patient safety indicators (PSIs) use inpatient administrative data to flag cases with potentially preventable adverse events (AEs) attributable to hospital care. This study explored how many AEs the PSIs identified in the 30 days post discharge. PSI software was run on Veterans Health Administration 2003-2007 administrative data for 10 recently validated PSIs. Among PSI-eligible index hospitalizations not flagged with an AE, this study evaluated how many AEs occurred within 1 to 14 and 15 to 30 days post discharge using inpatient and outpatient administrative data. Considering all PSI-eligible index hospitalizations, 11 141 postdischarge AEs were identified, compared with 40 578 inpatient-flagged AEs. More than 60% of postdischarge AEs were detected within 14 days of discharge. The majority of postdischarge AEs were decubitus ulcers and postoperative pulmonary embolisms or deep vein thromboses. Extending PSI algorithms to the postdischarge period may provide a more complete picture of hospital quality. Future work should use chart review to validate postdischarge PSI events. C1 [Mull, Hillary J.; Chen, Qi; Shin, Marlena H.; Rosen, Amy K.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Mull, Hillary J.; Borzecki, Ann M.; Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Borzecki, Ann M.] Bedford VAMC, Bedford, MA USA. RP Mull, HJ (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res COLMR, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM hillary.mull@va.gov FU Department of Veterans Affairs Health Services Research and Development Service [SDR 07-002] FX The authors received the following financial support for the research, authorship, and/or publication of this article: This work was supported by Department of Veterans Affairs Health Services Research and Development Service Grant Number SDR 07-002. NR 31 TC 3 Z9 3 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY PY 2014 VL 29 IS 3 BP 213 EP 219 DI 10.1177/1062860613494751 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AG6SJ UT WOS:000335548400005 PM 23939485 ER PT J AU Prentice, JC Davies, ML Pizer, SD AF Prentice, Julia C. Davies, Michael L. Pizer, Steven D. TI Which Outpatient Wait-Time Measures Are Related to Patient Satisfaction? SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE wait-time measures; access to care; VHA; VA; patient satisfaction ID HEALTH-CARE; ADVANCED ACCESS; INSURANCE; VETERANS; OUTCOMES AB Long waits for appointments decrease patient satisfaction. Administrative wait-time measures are used by managers, but relationships between these measures and satisfaction have not been studied. Data from the Veterans Health Administration are used to examine the relationship between wait times and satisfaction. Outcome measures include patient-reported satisfaction and timely appointment access. Capacity and retrospective and prospective time stamp measures are calculated separately for new and returning patients. The time stamp measures consist of the date when the appointment was created in the scheduling system (create date [CD]) or the date the appointment was desired as the start date for wait-time computation. Logistic regression models predict patient satisfaction using these measures. The new-patient capacity, new-patient time stamp measures using CD, and the returning-patient desired-date prospective measure were significantly associated with patient satisfaction. Standard practices can be improved by targeting wait-time measures to patient subpopulations. C1 [Prentice, Julia C.; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Prentice, Julia C.; Pizer, Steven D.] Sch Med, Boston, MA 02130 USA. [Davies, Michael L.] Natl Director Syst Redesign, Dept Vet Affairs, Ft Meade, SD USA. RP Prentice, JC (reprint author), Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, 150 S Huntington Ave,Mailstop 152H, Boston, MA 02130 USA. EM Julia.Prentice@va.gov FU Department of Veterans Affairs, Veterans Health Administration Systems Redesign office FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: Funding for this research was provided by the Department of Veterans Affairs, Veterans Health Administration Systems Redesign office. NR 28 TC 3 Z9 3 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY PY 2014 VL 29 IS 3 BP 227 EP 235 DI 10.1177/1062860613494750 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AG6SJ UT WOS:000335548400007 PM 23939488 ER PT J AU Boroughs, MS Thompson, JK AF Boroughs, Michael S. Thompson, J. Kevin TI Correlates of Body Depilation: An Exploratory Study Into the Health Implications of Body Hair Reduction and Removal Among College-Aged Men SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE body depilation; body hair; muscularity; masculinity; body dysmorphia; men's health ID RESISTANT STAPHYLOCOCCUS-AUREUS; DYSMORPHIC DISORDER; HAIRLESSNESS NORM; GENDER; IMAGE; INTERNET; WOMEN; FEMININITY; CULTURE; PLAYERS AB Recent studies suggest that body hair may be of increasing importance in men's overall body image. Body depilation is a relatively new area of clinical and research inquiry among men with much of the documented evidence of the phenomenon split between mass media accounts and descriptive scientific investigations. This study was undertaken to further our understanding of this behavior by examining the relationship between depilation and other dimensions of body image in a nonclinical sample. A total of 364 men completed measures assessing self-reported hair growth, body depilation, drive for muscularity, gender role conflict, body dysmorphia, and social comparison. The correlates of body depilation included a drive for muscularity, gender role conflict, and physical appearance social comparison. Significant differences were identified among men who depilate, compared with those who do not, on measures of social comparison and a drive for muscularity. These findings lend support for the idea that body hair, and its reduction or removal, is a key aspect of men's body image that translates into some challenges in assessment and prevention among health care practitioners. C1 [Boroughs, Michael S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boroughs, Michael S.] Harvard Univ, Sch Med, Boston, MA USA. [Thompson, J. Kevin] Univ S Florida, Tampa, FL USA. RP Boroughs, MS (reprint author), Massachusetts Gen Hosp, Behav Med Serv, One Bowdoin Sq, Boston, MA 02114 USA. EM mboroughs@mgh.harvard.edu NR 54 TC 4 Z9 4 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 EI 1557-9891 J9 AM J MENS HEALTH JI Am. J. Mens Health PD MAY PY 2014 VL 8 IS 3 BP 217 EP 225 DI 10.1177/1557988313506460 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AF0UP UT WOS:000334429900004 PM 24128670 ER PT J AU Chang, RSK Cole, AJ AF Chang, Richard Shek-Kwan Cole, Andrew J. TI Lamotrigine-Induced Lupus-Like Syndrome: A Case Report and Literature Review SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE lamotrigine; drug-induced lupus; epilepsy; adverse effect ID DRUG-INDUCED LUPUS AB Lamotrigine, as a new generation anticonvulsant, has been widely used in treating epilepsy. It is also a mood stabilizer for bipolar disorder. Common adverse effects include nausea and vomiting, dyspepsia, insomnia, somnolence, and rash. However, drug-induced lupus (DIL) due to lamotrigine has been rarely reported. We report a case of lupus-like syndrome associated with lamotrigine. A 39-year-old male developed arthralgias and positive serum antinuclear antibody repeatedly with introductions of lamotrigine. The strong temporal relationship between the rheumatological features and drug exposure is illustrative of the disease course of DIL. Two hitherto reported lamotrigine-related DIL cases are compared with our case. C1 [Chang, Richard Shek-Kwan] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, VBK 830,55 Fruit St, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 EI 1536-3686 J9 AM J THER JI Am. J. Ther. PD MAY-JUN PY 2014 VL 21 IS 3 BP E85 EP E87 DI 10.1097/MJT.0b013e3182491c31 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH2UT UT WOS:000335977800007 PM 23011169 ER PT J AU McDaniel, SH Grus, CL Cubic, BA Hunter, CL Kearney, LK Schuman, CC Karel, MJ Kessler, RS Larkin, KT McCutcheon, S Miller, BF Nash, J Qualls, SH Connolly, KS Stancin, T Stanton, AL Sturm, LA Johnson, SB AF McDaniel, Susan H. Grus, Catherine L. Cubic, Barbara A. Hunter, Christopher L. Kearney, Lisa K. Schuman, Catherine C. Karel, Michele J. Kessler, Rodger S. Larkin, Kevin T. McCutcheon, Stephen Miller, Benjamin F. Nash, Justin Qualls, Sara H. Connolly, Kathryn Sanders Stancin, Terry Stanton, Annette L. Sturm, Lynne A. Johnson, Suzanne Bennett TI Competencies for Psychology Practice in Primary Care SO AMERICAN PSYCHOLOGIST LA English DT Article DE primary care; competence; education and training ID CENTERED MEDICAL HOME; PROFESSIONAL PSYCHOLOGY; BEHAVIORAL HEALTH; POPULATION HEALTH; MODEL; EDUCATION; PROJECT; GEROPSYCHOLOGY; BENCHMARKS; SERVICES AB This article reports on the outcome of a presidential initiative of 2012 American Psychological Association President Suzanne Bennett Johnson to delineate competencies for primary care (PC) psychology in six broad domains: science, systems, professionalism, relationships, application, and education. Essential knowledge, skills, and attitudes are described for each PC psychology competency. Two behavioral examples are provided to illustrate each competency. Clinical vignettes demonstrate the competencies in action. Delineation of these competencies is intended to inform education, practice, and research in PC psychology and efforts to further develop team-based competencies in PC. C1 [McDaniel, Susan H.] Univ Rochester, Med Ctr, Inst Family, Dept Psychiat, Rochester, NY 14620 USA. [McDaniel, Susan H.] Univ Rochester, Med Ctr, Dept Family Med, Rochester, NY 14620 USA. [Grus, Catherine L.] Amer Psychol Assoc, Educ Directorate, Washington, DC 20036 USA. [Cubic, Barbara A.] Eastern Virginia Med Sch, Dept Family Med, Norfolk, VA USA. [Hunter, Christopher L.] Def Hlth Agcy, Patient Ctr Med Home Branch, Clin Support Div, Falls Church, VA USA. [Kearney, Lisa K.] Vet Hlth Adm, Off Mental Hlth Operat, Dept Vet Affairs, Cent Off, Washington, DC USA. [Kearney, Lisa K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Schuman, Catherine C.] Harvard Univ, Sch Med, Dept Psychiat, Div Psychol, Cambridge, MA 02138 USA. [Karel, Michele J.] Dept Vet Affairs, Off Mental Hlth Serv, Cent Off, Washington, DC USA. [Kessler, Rodger S.] Vermont Coll Med, Dept Family Med, Burlington, VT USA. [Larkin, Kevin T.] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. [McCutcheon, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Miller, Benjamin F.] Univ Colorado Denver, Sch Med, Dept Family Med, Denver, CO USA. [Nash, Justin] Brown Univ, Dept Family Med, Pawtucket, RI USA. [Nash, Justin] Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. [Qualls, Sara H.] Univ Colorado, Dept Psychol, Colorado Springs, CO 80933 USA. [Connolly, Kathryn Sanders] Vet Affairs Connecticut Healthcare Syst, Psychol Serv, West Haven, CT USA. [Connolly, Kathryn Sanders] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Stancin, Terry] MetroHlth Med Ctr, Div Child & Adolescent Psychiat & Psychol, Cleveland, OH USA. [Stancin, Terry] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Stanton, Annette L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Sturm, Lynne A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Johnson, Suzanne Bennett] Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA. RP McDaniel, SH (reprint author), Univ Rochester, Med Ctr, Dept Family Med, 777 S Clinton Ave, Rochester, NY 14620 USA. EM susanh2_mcdaniel@urmc.rochester.edu OI Miller, Benjamin/0000-0003-1647-0122 NR 71 TC 36 Z9 36 U1 2 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD MAY-JUN PY 2014 VL 69 IS 4 SI SI BP 409 EP 429 DI 10.1037/a0036072 PG 21 WC Psychology, Multidisciplinary SC Psychology GA AH5ER UT WOS:000336151800009 PM 24820690 ER PT J AU Tubelli, AA Zosuls, A Ketten, DR Mountain, DC AF Tubelli, Andrew A. Zosuls, Aleks Ketten, Darlene R. Mountain, David C. TI Elastic Modulus of Cetacean Auditory Ossicles SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE cetacean; ossicles; middle ear; hearing; elastic modulus ID BONE MECHANICAL-PROPERTIES; MIDDLE-EAR; CORTICAL BONE; BALAENOPTERA-ACUTOROSTRATA; TRABECULAR BONE; MINKE WHALE; NANOINDENTATION; TISSUE; LAMELLAE; HARDNESS AB In order to model the hearing capabilities of marine mammals (cetaceans), it is necessary to understand the mechanical properties, such as elastic modulus, of the middle ear bones in these species. Biologically realistic models can be used to investigate the biomechanics of hearing in cetaceans, much of which is currently unknown. In the present study, the elastic moduli of the auditory ossicles (malleus, incus, and stapes) of eight species of cetacean, two baleen whales (mysticete) and six toothed whales (odontocete), were measured using nanoindentation. The two groups of mysticete ossicles overall had lower average elastic moduli (35.2 +/- 13.3 GPa and 31.6 +/- 6.5 GPa) than the groups of odontocete ossicles (53.3 +/- 7.2 GPa to 62.3 +/- 4.7 GPa). Interior bone generally had a higher modulus than cortical bone by up to 36%. The effects of freezing and formalin-fixation on elastic modulus were also investigated, although samples were few and no clear trend could be discerned. The high elastic modulus of the ossicles and the differences in the elastic moduli between mysticetes and odontocetes are likely specializations in the bone for underwater hearing. Anat Rec, 297:892-900, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Tubelli, Andrew A.; Zosuls, Aleks; Mountain, David C.] Boston Univ, Hearing Res Ctr, Dept Biomed Engn, Boston, MA 02215 USA. [Ketten, Darlene R.] Woods Hole Oceanog Inst, Dept Biol, Marine Res Facil, Woods Hole, MA 02543 USA. [Ketten, Darlene R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Tubelli, AA (reprint author), Boston Univ, Hearing Res Ctr, 44 Cummington St, Boston, MA 02215 USA. EM atubelli@bu.edu OI Mountain, David/0000-0001-7537-9148 FU Living Marine Resources program [N00244-100-0053]; Joint Industry Program FX Grant sponsor: Joint Industry Program and the Living Marine Resources program; Grant number: N00244-100-0053. NR 44 TC 1 Z9 1 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8486 EI 1932-8494 J9 ANAT REC JI Anat. Rec. PD MAY PY 2014 VL 297 IS 5 BP 892 EP 900 DI 10.1002/ar.22896 PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA AF5XH UT WOS:000334787000012 PM 24523260 ER PT J AU Williams, BA Schott, NJ Mangione, MP Ibinson, JW AF Williams, Brian A. Schott, Nicholas J. Mangione, Michael P. Ibinson, James W. TI Perineural Dexamethasone and Multimodal Perineural Analgesia: How Much Is Too Much? SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID SCIATIC-NERVE BLOCK; ELIMINATING POSTOPERATIVE NAUSEA; OFF-PATENT ANTIEMETICS; OUTPATIENT SURGERY; LOCAL-ANESTHETICS; ROPIVACAINE; DURATION; RAT; DEXMEDETOMIDINE; METAANALYSIS C1 [Williams, Brian A.; Ibinson, James W.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Schott, Nicholas J.] UPMC, Dept Anesthesiol, Pittsburgh, PA USA. [Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. RP Williams, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, Vet Affairs Pittsburgh Healthcare Syst, 200 Lothrop St,A-1305, Pittsburgh, PA 15261 USA. EM Williamsba@anes.upmc.edu NR 20 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2014 VL 118 IS 5 BP 912 EP 914 DI 10.1213/ANE.0000000000000203 PG 3 WC Anesthesiology SC Anesthesiology GA AG4NE UT WOS:000335395900008 PM 24781562 ER PT J AU Bayes, J Gayer, S AF Bayes, Joseph Gayer, Steven TI Ophthalmic Anesthesia Society 2013 Annual Meeting Summary SO ANESTHESIA AND ANALGESIA LA English DT Article C1 [Bayes, Joseph] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. [Gayer, Steven] Univ Miami, Miller Sch Med, Dept Anesthesia, Bascom Palmer Eye Inst, Miami, FL 33136 USA. RP Bayes, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. EM joseph_bayes@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2014 VL 118 IS 5 BP 1143 EP 1144 DI 10.1213/ANE.0000000000000132 PG 2 WC Anesthesiology SC Anesthesiology GA AG4NE UT WOS:000335395900043 ER PT J AU Kruse, JL Jeffrey, JK Davis, MC Dearlove, J IsHak, WW Brooks, JO AF Kruse, Jennifer L. Jeffrey, Jessica K. Davis, Michael C. Dearlove, Joanna IsHak, Waguih William Brooks, John O., III TI Anti-N-methyl-D-aspartate receptor encephalitis: A targeted review of clinical presentation, diagnosis, and approaches to psychopharmacologic management SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Review DE N-methyl-D-aspartate receptor; limbic encephalitis; behavioral symptoms; benzodiazepines; antipsychotic agents ID NMDAR ENCEPHALITIS; ANTIBODIES; ADOLESCENTS; DISEASES; CHILDREN AB BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis was formally described in 2007 and includes a range of psychiatric and neurologic symptoms. Most patients with anti-NMDAR encephalitis initially present to psychiatrists for diagnosis and treatment. However, there is limited literature summarizing treatment strategies for psychiatric symptoms. In an effort to improve identification and treatment, this review article provides an overview of anti-NMDAR encephalitis, with a focus on psychopharmacologic treatment strategies. Two case reports provide a clinical context for the literature review. METHODS: The authors conducted a PubMed search. RESULTS: Prominent psychiatric symptoms of anti-NMDAR encephalitis include psychosis, agitation, insomnia, and catatonia. Neuroleptics may be helpful for managing psychosis and agitation, but may exacerbate movement abnormalities. Diphenhydramine and benzodiazepines are helpful for agitation and insomnia. In addition, the anticholinergic affinity of diphenhydramine can improve dystonia or rigidity attributable to anti-NMDAR encephalitis, while benzodiazepines and electroconvulsive therapy have been used for catatonia associated with this condition. CONCLUSIONS: Psychiatrists play an important role in the diagnosis and treatment of anti-NMDAR encephalitis. Recognizing the typical clinical progression and closely monitoring for accompanying neurologic symptoms will facilitate diagnosis and timely treatment. Careful selection of psychopharmacological interventions may reduce suffering. C1 [Kruse, Jennifer L.; Jeffrey, Jessica K.; Davis, Michael C.; Brooks, John O., III] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Kruse, Jennifer L.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Davis, Michael C.] VA Greater Los Angeles, Los Angeles, CA USA. [Dearlove, Joanna] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [IsHak, Waguih William] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Dept Psychiat & Behav Neurosci,Cedars Sinai Med C, Los Angeles, CA 90095 USA. RP Brooks, JO (reprint author), UCLA Semel Inst, 760 Westwood Plaza,B3-267, Los Angeles, CA 90024 USA. EM john.brooks@ucla.edu RI Davis, Michael/L-8920-2013 OI Davis, Michael/0000-0003-2293-5694 FU Pfizer FX Dr. Brooks has received a research grant from Pfizer, and is a speaker for Sunovion. Drs. Kruse, Jeffrey, Davis, Dearlove, and IsHak report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products. NR 23 TC 15 Z9 15 U1 1 U2 5 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 EI 1547-3325 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD MAY PY 2014 VL 26 IS 2 BP 111 EP 119 PG 9 WC Psychiatry SC Psychiatry GA AH7WX UT WOS:000336347200005 PM 24501734 ER PT J AU Klein, MB Goverman, J Hayden, DL Fagan, SP McDonald-Smith, GP Alexander, AK Gamelli, RL Gibran, NS Finnerty, CC Jeschke, MG Arnoldo, B Wispelwey, B Mindrinos, MN Xiao, WZ Honari, SE Mason, PH Schoenfeld, DA Herndon, DN Tompkins, RG AF Klein, Matthew B. Goverman, Jeremy Hayden, Douglas L. Fagan, Shawn P. McDonald-Smith, Grace P. Alexander, Andrew K. Gamelli, Richard L. Gibran, Nicole S. Finnerty, Celeste C. Jeschke, Marc G. Arnoldo, Brett Wispelwey, Bram Mindrinos, Michael N. Xiao, Wenzhong Honari, Shari E. Mason, Philip H. Schoenfeld, David A. Herndon, David N. Tompkins, Ronald G. CA Inflammation Host Response Injury Large-Scale Collaborative Res TI Benchmarking Outcomes in the Critically Injured Burn Patient SO ANNALS OF SURGERY LA English DT Article DE benchmark; burns; inhalation injury; mortality; organ failure; outcomes ID RESPIRATORY-DISTRESS-SYNDROME; STANDARD OPERATING PROCEDURES; MULTIPLE ORGAN FAILURE; PROMPT ESCHAR EXCISION; MORTALITY; CARE; MANAGEMENT; QUALITY; DEATH AB Objective: To determine and compare outcomes with accepted benchmarks in burn care at 6 academic burn centers. Background: Since the 1960s, US morbidity and mortality rates have declined tremendously for burn patients, likely related to improvements in surgical and critical care treatment. We describe the baseline patient characteristics and well-defined outcomes for major burn injuries. Methods: We followed 300 adults and 241 children from 2003 to 2009 through hospitalization, using standard operating procedures developed at study onset. We created an extensive database on patient and injury characteristics, anatomic and physiological derangement, clinical treatment, and outcomes. These data were compared with existing benchmarks in burn care. Results: Study patients were critically injured, as demonstrated by mean % total body surface area (TBSA) (41.2 18.3 for adults and 57.8 +/- 18.2 for children) and presence of inhalation injury in 38% of the adults and 54.8% of the children. Mortality in adults was 14.1% for those younger than 55 years and 38.5% for those aged 55 years and older. Mortality in patients younger than 17 years was 7.9%. Overall, the multiple organ failure rate was 27%. When controlling for age and % TBSA, presence of inhalation injury continues to be significant. Conclusions: This study provides the current benchmark for major burn patients. Mortality rates, notwithstanding significant % TBSA and presence of inhalation injury, have significantly declined compared with previous benchmarks. Modern day surgical and medically intensive management has markedly improved to the point where we can expect patients younger than 55 years with severe burn injuries and inhalation injury to survive these devastating conditions. C1 [Klein, Matthew B.; Gibran, Nicole S.] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Klein, Matthew B.; Gibran, Nicole S.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Goverman, Jeremy; Tompkins, Ronald G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Goverman, Jeremy; Fagan, Shawn P.; Xiao, Wenzhong; Schoenfeld, David A.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hayden, Douglas L.; Wispelwey, Bram] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McDonald-Smith, Grace P.; Alexander, Andrew K.; Mason, Philip H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gamelli, Richard L.] Loyola Univ, Dept Surg, Sch Med, Maywood, IL 60153 USA. [Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Jeschke, Marc G.] Univ Toronto, Dept Surg & Plast Surg, Toronto, ON M5S 1A1, Canada. [Arnoldo, Brett] Univ Texas SW Med Ctr Dallas, Dept Surg, Parkland Mem Hosp, Dallas, TX 75390 USA. [Mindrinos, Michael N.] Stanford Genome Technol Ctr, Palo Alto, CA USA. [Honari, Shari E.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Schoenfeld, David A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Tompkins, RG (reprint author), Harvard Univ, Sch Med, 55 Fruit St,GRB 1302, Boston, MA 02114 USA. EM rtompkins@mgh.harvard.edu FU National Institute of General Medical Sciences [5U54GM062119] FX This study was supported by the Inflammation and the Host Response to Injury Large-Scale Collaborative Research Grant from the National Institute of General Medical Sciences, 5U54GM062119. The authors declare no conflicts of interest. NR 25 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2014 VL 259 IS 5 BP 833 EP 841 DI 10.1097/SLA.0000000000000438 PG 9 WC Surgery SC Surgery GA AH2BK UT WOS:000335925500007 PM 24722222 ER PT J AU Sahani, DV Bajwa, MA Andrabi, Y Bajpai, S Cusack, JC AF Sahani, Dushyant V. Bajwa, Mohammad Ali Andrabi, Yasir Bajpai, Surabhi Cusack, James C. TI Current Status of Imaging and Emerging Techniques to Evaluate Liver Metastases From Colorectal Carcinoma SO ANNALS OF SURGERY LA English DT Review DE colorectal cancer; imaging; liver metastases; treatment options; treatment response monitoring ID POSITRON-EMISSION-TOMOGRAPHY; SPIO-ENHANCED MRI; PORTAL-VEIN EMBOLIZATION; BODY RADIATION-THERAPY; DIFFUSION-WEIGHTED MRI; HEPATIC RESECTION; COMPUTED-TOMOGRAPHY; INTRAOPERATIVE ULTRASOUND; DIAGNOSTIC-ACCURACY; FDG-PET AB Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. Liver is a common site of tumor spread and in approximately 30% of the cases; synchronous liver disease is present at the time of diagnosis. Early detection of liver metastases is crucial to appropriately select patients who may benefit from hepatic resection among those needing chemotherapy, to improve 5-year survival. Advances in imaging techniques have contributed greatly to the management of these patients. Multidetector computed tomography is the most useful test for initial staging and in posttreatment surveillance settings. Magnetic resonance imaging is considered superior to multidetector computed tomography and positron emission tomography for the detection and characterization of small lesions and for liver evaluation in the presence of background fatty liver changes. Positron emission tomography-computed tomography has a problem-solving role in the detection of distant metastasis and in posttreatment evaluation. The advanced imaging methods also serve a role in selecting appropriate patients for radiologically targeted therapies and in monitoring response to conventional and novel therapies. C1 [Sahani, Dushyant V.; Bajwa, Mohammad Ali; Andrabi, Yasir; Bajpai, Surabhi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Cusack, James C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 119 TC 18 Z9 19 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2014 VL 259 IS 5 BP 861 EP 872 DI 10.1097/SLA.0000000000000525 PG 12 WC Surgery SC Surgery GA AH2BK UT WOS:000335925500012 PM 24509207 ER PT J AU Fiore, M Coppola, S Cannell, AJ Colombo, C Bertagnolli, MM George, S Le Cesne, A Gladdy, RA Casali, PG Swallow, CJ Gronchi, A Bonvalot, S Raut, CP AF Fiore, Marco Coppola, Sara Cannell, Amanda J. Colombo, Chiara Bertagnolli, Monica M. George, Suzanne Le Cesne, Axel Gladdy, Rebecca A. Casali, Paolo G. Swallow, Carol J. Gronchi, Alessandro Bonvalot, Sylvie Raut, Chandrajit P. TI Desmoid-Type Fibromatosis and Pregnancy A Multi-institutional Analysis of Recurrence and Obstetric Risk SO ANNALS OF SURGERY LA English DT Article DE aggressive fibromatosis; desmoid-type fibromatosis; pregnancy; prognosis; wait and see ID AGGRESSIVE FIBROMATOSIS; ABDOMINAL-WALL; TUMORS; EXPRESSION; RECEPTOR; DISEASE; SERIES AB Background: Many women who present with desmoid-type fibromatosis (DF) have had a recent pregnancy. Long-term data about disease behavior during and after pregnancy are lacking. Objective: To investigate the possible relationship between DF and pregnancy. Patients and Methods: A cohort of women with DF and pregnancy was identified from 4 sarcoma centers. Four groups were identified: diagnosis during pregnancy (A); diagnosis after delivery (B); DF clinically evident during pregnancy (C); and DF resected before pregnancy (D). Progression/regression rates, recurrence rates after resection, and obstetric outcomes were analyzed. Results: Ninety-two women were included. Forty-four women (48%) had pregnancy-related DF (A + B), whereas 48 (52%) had a history of DF before conception (C + D). Initial treatment was resection in 52%, medical therapy in 4%, and watchful waiting in 43%. Postsurgical relapse rate in A + B was 13%, although progression during watchful waiting was 63%. Relapse/progression in C + D was 42%. After pregnancy, 46% underwent treatment of DF, whereas 54% were managed with watchful waiting. Eventually, only 17% experienced further progression after treatment. Spontaneous regression occurred in 14%. After further pregnancies, only 27% progressed. The only related obstetric event was a cesarean delivery. Conclusions: Pregnancy-related DF has good outcomes. Progression risk during pregnancy is high, but it can be safely managed. DF does not increase obstetric risk, and it should not be a contraindication to future pregnancy. C1 [Fiore, Marco; Colombo, Chiara; Gronchi, Alessandro] Fdn IRCCS Ist Nazl Tumori, Dept Surg, I-20133 Milan, Italy. [Coppola, Sara; Bonvalot, Sylvie] Inst Gustave Roussy, Dept Surg, Villejuif, France. [Cannell, Amanda J.; Gladdy, Rebecca A.; Swallow, Carol J.] Univ Toronto, Mt Sinai Hosp, Div Gen Surg, Toronto, ON M5G 1X5, Canada. [Cannell, Amanda J.; Gladdy, Rebecca A.; Swallow, Carol J.] Univ Toronto, Dept Surg Oncol, Princess Margaret Hosp, Toronto, ON, Canada. [Cannell, Amanda J.; Gladdy, Rebecca A.; Swallow, Carol J.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Bertagnolli, Monica M.; Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Med Sch, Boston, MA 02115 USA. [George, Suzanne] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Med Sch, Boston, MA 02115 USA. [Le Cesne, Axel] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Casali, Paolo G.] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, I-20133 Milan, Italy. RP Fiore, M (reprint author), Fdn IRCCS Ist Nazl Tumori, Dept Surg, Via Venezian 1, I-20133 Milan, Italy. EM marco.fiore@istitutotumori.mi.it; craut@partners.org RI Gladdy, Rebecca/A-2516-2013; Fiore, Marco/M-6587-2016; Colombo, Chiara/C-4303-2017; casali, Paolo Giovanni/D-1524-2017; OI Gladdy, Rebecca/0000-0003-4143-6620; Fiore, Marco/0000-0001-8220-424X; Colombo, Chiara/0000-0001-8031-5528; casali, Paolo Giovanni/0000-0003-4056-8023; Gronchi, Alessandro/0000-0002-4703-3534 NR 26 TC 18 Z9 18 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD MAY PY 2014 VL 259 IS 5 BP 973 EP 978 DI 10.1097/SLA.0000000000000224 PG 6 WC Surgery SC Surgery GA AH2BK UT WOS:000335925500027 PM 24477160 ER PT J AU Hoogeveen, RC Gaubatz, JW Sun, WS Dodge, RC Crosby, JR Jiang, J Couper, D Virani, SS Kathiresan, S Boerwinkle, E Ballantyne, CM AF Hoogeveen, Ron C. Gaubatz, John W. Sun, Wensheng Dodge, Rhiannon C. Crosby, Jacy R. Jiang, Jennifer Couper, David Virani, Salim S. Kathiresan, Sekar Boerwinkle, Eric Ballantyne, Christie M. TI Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease The Atherosclerosis Risk in Communities ( ARIC) Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary disease; genome-wide association study; triglycerides ID MAGNETIC-RESONANCE-SPECTROSCOPY; GENOME-WIDE ASSOCIATION; TREATMENT PANEL-III; LDL PARTICLE-SIZE; PROPROTEIN CONVERTASES; MYOCARDIAL-INFARCTION; ARTERY DISEASE; LIPASE ACTIVITY; TRIGLYCERIDE; VARIANTS AB Objective To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. Approach and Results Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of approximate to 11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non-diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21-1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04-2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. Conclusions sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism. C1 [Hoogeveen, Ron C.; Gaubatz, John W.; Sun, Wensheng; Jiang, Jennifer; Virani, Salim S.; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hoogeveen, Ron C.; Gaubatz, John W.; Sun, Wensheng; Jiang, Jennifer; Virani, Salim S.; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Dodge, Rhiannon C.; Crosby, Jacy R.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Virani, Salim S.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Hoogeveen, RC (reprint author), Baylor Coll Med, Dept Med, Mail Stn F701,6565 Fannin St, Houston, TX 77030 USA. EM ronh@bcm.tmc.edu OI Virani, Salim/0000-0001-9541-6954 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human Genome Research Institute [U01HG004402]; NIH [HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research; Department of Veterans Affairs Health Services Research; Development Career Development Grant; [R01HL087641]; [R01HL59367]; [R01HL086694] FX The Atherosclerosis Risk in Communities (ARIC) Study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The support for the exome chip geno-typing and centralized calling was provided by Building on genome-wide association study (GWAS) for NHLBI-diseases: the US CHARGE consortium through the National Institutes of Health (NIH) American Recovery and Reinvestment Act of 2009 (ARRA; 5RC2HL102419; PI: Dr Boerwinkle). GWA support was funded by R01HL087641, R01HL59367, R01HL086694, National Human Genome Research Institute contract U01HG004402, and NIH contract HHSN268200625226C. The infrastructure was partly supported by grant UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. Dr Virani is supported by a Department of Veterans Affairs Health Services Research and Development Career Development Grant. NR 43 TC 63 Z9 69 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2014 VL 34 IS 5 BP 1069 EP 1077 DI 10.1161/ATVBAHA.114.303284 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AF0AJ UT WOS:000334373500018 PM 24558110 ER PT J AU Huang, J Huffman, JE Yamkauchi, M Trompet, S Asselbergs, FW Sabater-Lleal, M Tregouet, DA Chen, WM Smith, NL Kleber, ME Shin, SY Becker, DM Tang, WH Dehghan, A Johnson, AD Truong, V Folkersen, L Yang, Q Oudot-Mellkah, T Buckley, BM Moore, JH Williams, FMK Campbell, H Silbernagel, G Vitart, V Rudan, I Tofler, GH Navis, GJ DeStefano, A Wright, AF Chen, MH de Craen, AJM Worrall, BB Rudnicka, AR Rumley, A Bookman, EB Psaty, BM Chen, F Keene, KL Franco, OH Bohm, BO Uitterlinden, AG Carter, AM Jukema, JW Sattar, N Bis, JC Ikram, MA Sale, MM McKnight, B Fornage, M Ford, I Taylor, K Slagboom, PE McArdle, WL Hsu, FC Franco-Cereceda, A Goodall, AH Yanek, LR Furie, KL Cushman, M Hofman, A Witteman, JCM Folsom, AR Basu, S Matijevic, N van Gilst, WH Wilson, JF Westendorp, RGJ Kathiresan, S Reilly, MP Tracy, RP Polasek, O Winkelmann, BR Grant, PJ Hillege, HL Cambien, F Stott, DJ Lowe, GD Spector, TD Meigs, JB Marz, W Eriksson, P Becker, LC Morange, PE Soranzo, N Williams, SM Hayward, C van der Harst, P Hamsten, A Lowenstein, CJ Strachan, DP O'Donnell, CJ AF Huang, Jie Huffman, Jennifer E. Yamkauchi, Munekazu Trompet, Stella Asselbergs, Folkert W. Sabater-Lleal, Maria Tregouet, David-Alexandre Chen, Wei-Min Smith, Nicholas L. Kleber, Marcus E. Shin, So-Youn Becker, Diane M. Tang, Weihong Dehghan, Abbas Johnson, Andrew D. Vinh Truong Folkersen, Lasse Yang, Qiong Oudot-Mellkah, Tiphaine Buckley, Brendan M. Moore, Jason H. Williams, Frances M. K. Campbell, Harry Silbernagel, Guenther Vitart, Veronique Rudan, Igor Tofler, Geoffrey H. Navis, Gerjan J. DeStefano, Anita Wright, Alan F. Chen, Ming-Huei de Craen, Anton J. M. Worrall, Bradford B. Rudnicka, Alicja R. Rumley, Ann Bookman, Ebony B. Psaty, Bruce M. Chen, Fang Keene, Keith L. Franco, Oscar H. Boehm, Bernhard O. Uitterlinden, Andre G. Carter, Angela M. Jukema, J. Wouter Sattar, Naveed Bis, Joshua C. Ikram, Mohammad A. Sale, Michele M. McKnight, Barbara Fornage, Myriam Ford, Ian Taylor, Kent Slagboom, P. Eline McArdle, Wendy L. Hsu, Fang-Chi Franco-Cereceda, Anders Goodall, Alison H. Yanek, Lisa R. Furie, Karen L. Cushman, Mary Hofman, Albert Witteman, Jacqueline C. M. Folsom, Aaron R. Basu, Saonli Matijevic, Nena van Gilst, Wiek H. Wilson, James F. Westendorp, Rudi G. J. Kathiresan, Sekar Reilly, Muredach P. Tracy, Russell P. Polasek, Ozren Winkelmann, Bernhard R. Grant, Peter J. Hillege, Hans L. Cambien, Francois Stott, David J. Lowe, Gordon D. Spector, Timothy D. Meigs, James B. Marz, Winfried Eriksson, Per Becker, Lewis C. Morange, Pierre-Emmanuel Soranzo, Nicole Williams, Scott M. Hayward, Caroline van der Harst, Pim Hamsten, Anders Lowenstein, Charles J. Strachan, David P. O'Donnell, Christopher J. CA CHARGE Consortium Hemostatic TI Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE fibrinolysis; genome-wide association study; hemostasis; meta-analysis; tissue plasminogen activator ID VON-WILLEBRAND-FACTOR; CORONARY-ARTERY-DISEASE; ACUTE ISCHEMIC-STROKE; MYOCARDIAL-INFARCTION; PLASMA-LEVELS; GENETIC-VARIATION; RISK; HEART; POLYMORPHISMS; INHIBITOR-1 AB Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA. Approach and Results Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0x10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9x10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3x10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0x10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0x10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke. Conclusions We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. C1 [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Huffman, Jennifer E.; Vitart, Veronique; Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Yamkauchi, Munekazu; Lowenstein, Charles J.] Univ Rochester, Sch Med & Dent, Dept Med, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RA Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RA Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RA Leiden, Netherlands. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [Asselbergs, Folkert W.] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England. [Sabater-Lleal, Maria; Folkersen, Lasse; Slagboom, P. Eline; Hofman, Albert] Karolinska Univ Hosp, Karolinska Inst, Cardiovasc Genet & Genom Grp, Atherosclerosis Res Unit,Dept Med, Stockholm, Sweden. [Tregouet, David-Alexandre; Vinh Truong; Oudot-Mellkah, Tiphaine; Chen, Fang] Univ Paris 06, INSERM, UMRS 937, Paris, France. [Tregouet, David-Alexandre; Vinh Truong; Chen, Fang] ICAN Inst Cardiometab & Nutr, Paris, France. [Chen, Wei-Min; Worrall, Bradford B.; Chen, Fang] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Smith, Nicholas L.; Psaty, Bruce M.; McKnight, Barbara] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA USA. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, VA Off Res & Dev, Seattle, WA USA. [Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89069 Ulm, Germany. [Kleber, Marcus E.; McArdle, Wendy L.] Heidelberg Univ, Mannheim Inst Publ Hlth, Med Fac Mannheim, Mannheim, Germany. [Shin, So-Youn; Sattar, Naveed] Wellcome Trust Sanger Inst, Hinxton, England. [Shin, So-Youn] Univ Bristol, MRC Ctr CAiTE, Sch Social & Community Med, Bristol, Avon, England. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Dept Social Med, Bristol, Avon, England. [Becker, Diane M.; Yanek, Lisa R.; Becker, Lewis C.] Johns Hopkins Sch Med, Div Internal Med, Baltimore, MD USA. [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Dehghan, Abbas; Franco, Oscar H.; Ikram, Mohammad A.; Goodall, Alison H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.; Grant, Peter J.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Ikram, Mohammad A.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Ikram, Mohammad A.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Dehghan, Abbas; Franco, Oscar H.; Uitterlinden, Andre G.; Slagboom, P. Eline; Goodall, Alison H.; Witteman, Jacqueline C. M.; Westendorp, Rudi G. J.] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Yang, Qiong; DeStefano, Anita; Chen, Ming-Huei] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Moore, Jason H.; Williams, Scott M.] Gesiel Sch Med Dartmouth, Dept Genet, Lebanon, NH USA. [Moore, Jason H.] Gesiel Sch Med Dartmouth, Dept Community & Family Med, Lebanon, NH USA. [Williams, Frances M. K.; Spector, Timothy D.; Soranzo, Nicole] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Silbernagel, Guenther] Swiss Cardiovasc Ctr, Dept Angiol, Bern, Switzerland. [Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Navis, Gerjan J.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [van Gilst, Wiek H.; Hillege, Hans L.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Rudnicka, Alicja R.; Strachan, David P.] St Georges Univ London, Div Populat Hlth Sci & Educ, London, England. [Rumley, Ann; Stott, David J.; Lowe, Gordon D.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Bookman, Ebony B.] NHGRI, Div Genom Med, Framingham, MA USA. [Keene, Keith L.] E Carolina Univ, Dept Biol, Greenville, NC USA. [Keene, Keith L.] E Carolina Univ, Ctr Hlth Dispar Res, Greenville, NC USA. [Boehm, Bernhard O.] Nanyang Technol Univ, LKC Sch Med, Singapore 639798, Singapore. [Carter, Angela M.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA. [Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Hemostasis Lab, Houston, TX 77030 USA. [Taylor, Kent] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden. [Goodall, Alison H.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Keene, Keith L.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Cushman, Mary; Tracy, Russell P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Polasek, Ozren] Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia. [Winkelmann, Bernhard R.] Cardiol Team Sachsenhausen, Frankfurt, Germany. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Marz, Winfried] Synlab Acad, Mannheim, Germany. [Marz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria. [Marz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria. [Morange, Pierre-Emmanuel] Aix Marseille Univ, INSERM, UMRS 1062, Marseille, France. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte St,2nd Floor, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Boehm, Bernhard/F-8750-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Tregouet, David-Alexandre/E-3961-2016; Rudan, Igor/I-1467-2012; Hayward, Caroline/M-8818-2016; Johnson, Andrew/G-6520-2013; Slagboom, P. Eline/R-4790-2016; OI Soranzo, Nicole/0000-0003-1095-3852; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Rudan, Igor/0000-0001-6993-6884; Hayward, Caroline/0000-0002-9405-9550; Slagboom, P. Eline/0000-0002-2875-4723; Williams, Frances/0000-0002-2998-2744; Folkersen, Lasse/0000-0003-0708-9530; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Sabater Lleal, Maria/0000-0002-0128-379X FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Swedish Research Council [12660]; Stockholm County Council [20090077]; Swedish Heart-Lung Foundation [20090541, 8691]; European Commission (FAD) [Health F2 2008 200647]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); Juvenile Diabetes Research Foundation International; Wellcome Trust; National Institute for Health Research (NIHR); Cambridge Biomedical Research Centre; Wellcome Trust Strategic Award [079895]; EU [018996, LSHM-CT-2006-037593]; French Ministry of Research; NHLBI [HHSN268201200036C, N01HC85239, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756, N01-HC-35129, N01 HC-15103, N01-HC-75150, N01-HC-45133]; National Institute of Neurological Disorders and Stroke NINDS; National Institute on Aging (NIA) [AG023629]; National Center for Research Resources [UL1RR033176]; National Center for Advancing Translational Sciences, Clinical & Translational Science Institute [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease grant [DK063491]; Medical Research Council UK; Ministry of Science, Education, and Sport of the Republic of Croatia [108-10803150302]; EU 6th Framework Programme EUROSPAN project [LSHG-CT-2006-018947]; NHLBI's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; GeneSTAR from the National Institutes of Health (NIH) [1U01 HL072518, R01 HL59684]; Johns Hopkins University School of Medicine General Clinical Research Center; NIH [M01 RR00052, LM010098, HL65234, HL67466, RR018787, P01 HL56091, R01 HL074061, R01 HL78635, P01 HL65608]; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Torsten and Ragnar Sderberg Foundation; Strategic Cardiovascular Program of Karolinska Institutet; Stockholm County Council; Foundation for Strategic Research; Marie Curie Intra European Fellowship within the EU [PIEF-GA-2009-252361]; EU 6th Framework Programme [LSHG-CT-2006-018947, LSHM-CT-2004-503485]; EU 7th Framework Programme (Atheroremo) [201668]; EU 7th Framework Programme (RiskyCAD) [305739]; Program Hospitalier de Recherche Clinique; Fondation pour la Recherche Medicale; La Region Ile de France (CODDIM); Genomic Network of the Pierre and Marie Curie University, Paris; Chief Scientist Office of the Scottish Government; Royal Society; Wellcome Trust Clinical Research Facility in Edinburgh, United Kingdom; Dutch Kidney Foundation [E033]; Netherlands Heart Foundation [2006B140, 2006T003, 2001 D 032]; EU project grant GENECURE [2006037697]; NWO VENI [91676170]; Dutch Inter University Cardiology Institute Netherlands (ICIN); Netherlands Organization for Health Research and Development (ZonMw) [90700342]; Bristol-Myers Squibb; 7th Framework Programme of the European commission [223004]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]; Scottish Executive Chief Scientist Office, Health Services Research Committee [CZG/4/306]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for ZonMw; Research Institute for Diseases in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; NWO [175.010.2005.011, 911-03-012, 918-76-619, 916.12.154]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; EUR Fellowship; European Community [005268]; ENGAGE project [HEALTH-F4-2007-201413]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; Department of Health via the NIHR comprehensive Biomedical Research Centre; Biotechnology and Biological Sciences Research Council (BBSRC) project [G20234]; National Eye Institute via an NIH/Center for Inherited Disease Research (CIDR) genotyping project; Oak Foundation; American Heart Association (AHA) [EIG 0140210N]; Paul N. Yu Professorship; AHA [0835446N]; National Human Genome Research Institute (NHGRI) [U01 HG005160]; NIH; United States Public Health Service [R01 NS34447]; NINDS/NIH; ARIC [U01 HL096917, R01-HL093029]; NIA [AG-023629, AG-15928, AG-20098, AG-027058, NS17950, AG08122, AG033193]; NINDS; [U01 DK062418] FX The Atherosclerosis Risk in Communities (ARIC) study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Advanced Study of Aortic Pathology (ASAP) work was supported by the Swedish Research Council (12660), the Stockholm County Council (20090077), the Swedish Heart-Lung Foundation (20090541), the European Commission (FAD, Health F2 2008 200647), and a donation by Fredrik Lundberg. British 1958 Birth Cohort (B58C) was funded by the Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02; http://www.b58cgene.sgul.ac.uk/). Genotyping for the B58C-WTCCC subset was funded by the Wellcome Trust (grant 076113/B/04/Z). The B58C-T1DGC genotyping used resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF), and supported by U01 DK062418. B58CT1DGC genome-wide association study (GWAS) data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, which is funded by Juvenile Diabetes Research Foundation International, the Wellcome Trust, and the National Institute for Health Research (NIHR), Cambridge Biomedical Research Centre; the CIMR is in receipt of a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the EU 6th Framework Programme (018996) and grants from the French Ministry of Research. CardioGenics was funded by the EU 6th Framework Programme (LSHM-CT-2006-037593). The Cardiovascular Health Study (CHS) was supported by NHLBI contracts HHSN268201200036C, N01HC85239, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at - http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping at Cedars-Sinai Medical Center was supported in part by the National Center for Research Resources (grant UL1RR033176) and is now at the National Center for Advancing Translational Sciences, Clinical & Translational Science Institute (grant UL1TR000124), in addition to the National Institute of Diabetes and Digestive and Kidney Disease grant (DK063491) to the Southern California Diabetes Endocrinology Research Center. The CROATIAVis study in the Croatian island of Vis was supported through the grants from the Medical Research Council UK and Ministry of Science, Education, and Sport of the Republic of Croatia (number 108-10803150302) and the EU 6th Framework Programme EUROSPAN project (contract no. LSHG-CT-2006-018947). The Framingham Heart Study was partially supported by NHLBI's Framingham Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (contract no. N02-HL-6-4278).; A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Partial investigator support was provided by National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140, to J. B. M). GeneSTAR was supported by grants 1U01 HL072518 and R01 HL59684 from the National Institutes of Health (NIH) and the Johns Hopkins University School of Medicine General Clinical Research Center, and the NIH grant M01 RR00052. The Precocious Coronary Artery Disease Study (PROCARDIS) was supported by the Swedish Research Council (8691), the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Sderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research, and the Stockholm County Council. M. S.-L. is a recipient of a Marie Curie Intra European Fellowship within the EU 7th Framework Programme (PIEF-GA-2009-252361). The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study has received funding from the EU 6th Framework Programme (integrated project Bloodomics; grant LSHM-CT-2004-503485) and from the EU 7th Framework Programme (Atheroremo, grant agreement no. 201668; RiskyCAD, grant agreement no. 305739). The Marseille Thrombosis Association (MARTHA) project was supported by a grant from the Program Hospitalier de Recherche Clinique. T.O.M. was supported by a grant from the Fondation pour la Recherche Medicale. Statistical analyses in MARTHA benefit from the C2BIG Computing Centre funded by the Fondation pour la Recherche Medicale, La Region Ile de France (CODDIM), and the Genomic Network of the Pierre and Marie Curie University, Paris. The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, and the EU 6th Framework Programme EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh, United Kingdom. Prevention of Renal and Vascular Endstage Disease (PREVEND) genetics is supported by the Dutch Kidney Foundation (grant E033), The Netherlands Heart Foundation (grant 2006B140, 2006T003), NIH (grants LM010098, HL65234, HL67466, RR018787), and the EU project grant GENECURE (FP-6 LSHM CT 2006037697). P.v.d.H. is supported by the NWO VENI grant 91676170 and the Dutch Inter University Cardiology Institute Netherlands (ICIN). F.W.A. is supported by a clinical fellowship from the Netherlands Organization for Health Research and Development (ZonMw; grant 90700342). Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER) was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. J.W.J. is an established clinical investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping for the PROSPER/ Pharmacogenetic Study of Statins in the Elderly at Risk (PHASE) study was provided by the 7th Framework Programme of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging; grant 050-060-810). Measurement of plasma tissue plasminogen activator was funded by the Scottish Executive Chief Scientist Office, Health Services Research Committee grant number CZG/4/306.; The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for ZonMw, the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Heart Foundation, the Ministry of Education, Culture and Science, the Ministry of Health Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Support for genotyping was provided by NWO (no. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project no. 050-060-810. J.C.M.W. is supported by NWO grant (vici, 918-76-619). A.D. is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship. The Twins UK study was funded by the Wellcome Trust, European Community's 6th and 7th Framework Programmes (FP-6/2005-2008, FP7/2007-2013) LIFE SCIENCES & HEALTH (Ref 005268 Genetic regulation of the end stage clotting process that leads to thrombotic stroke: the EuroClot Consortium), ENGAGE project HEALTH-F4-2007-201413 and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The study also received support from the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. T.D.S. is an NIHR Senior Investigator. The project also received support from a Biotechnology and Biological Sciences Research Council (BBSRC) project grant (G20234). The authors acknowledge the funding and support of the National Eye Institute via an NIH/Center for Inherited Disease Research (CIDR) genotyping project (PI: Terri Young). S.-Y.S. is supported by a Post-Doctoral Research Fellowship from the Oak Foundation. Research at the University of Rochester was supported by grants from the NIH (P01 HL56091, R01 HL074061, R01 HL78635, P01 HL65608), American Heart Association (AHA; EIG 0140210N), and the Paul N. Yu Professorship to C.J.L. Supported by grants from the AHA (0835446N) to M. Y. The GWAS component of the Vitamin Intervention for Stroke Prevention (VISP) study was supported by the National Human Genome Research Institute (NHGRI) grant U01 HG005160 (PIs: Michele Sale amd Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University's CIDR, which is fully funded through a federal contract from the NIH to the Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI: Bruce S. Weir). Study recruitment and collection of data sets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI: James Toole) from the United States Public Health Service, NINDS/NIH. The Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium Neurology Working Group was supported by U01 HL096917 and R01-HL093029 for ARIC; by NHLBI contracts N01-HC-35129, N01 HC-15103, N01-HC-75150, N01-HC-45133, and AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA, for CHS; and by NINDS and NIA grants NS17950, AG08122, and AG033193 for Framingham Heart Study. NR 29 TC 14 Z9 14 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2014 VL 34 IS 5 BP 1093 EP 1101 DI 10.1161/ATVBAHA.113.302088 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AF0AJ UT WOS:000334373500021 PM 24578379 ER PT J AU Saylor, PJ AF Saylor, Philip J. TI Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer SO ASIAN JOURNAL OF ANDROLOGY LA English DT Review DE denosumab; osteoporosis; osteopenia; osteoclast; RANK (receptor activator of nuclear factor-kappa B); skeletal-related events ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; ORAL SODIUM CLODRONATE; PLACEBO-CONTROLLED TRIAL; ZOLEDRONIC ACID; FRACTURE RISK; DOUBLE-BLIND; POSTMENOPAUSAL WOMEN; COST-EFFECTIVENESS; MINERAL DENSITY AB Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-k-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed. C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. EM psaylor@partners.org FU Prostate Cancer Foundation FX Dr. Philip J Saylor is supported by a Young Investigator Award from the Prostate Cancer Foundation. NR 79 TC 4 Z9 5 U1 1 U2 6 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1008-682X EI 1745-7262 J9 ASIAN J ANDROL JI Asian J. Androl. PD MAY PY 2014 VL 16 IS 3 BP 341 EP 347 DI 10.4103/1008-682X.122591 PG 7 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA AH4FI UT WOS:000336082200003 PM 24435057 ER PT J AU Nasri, HZ Deutsch, CK Holmes, LB AF Nasri, H. Z. Deutsch, C. K. Holmes, L. B. TI Quantifying the "Anticonvulsant Face" SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Nasri, H. Z.; Holmes, L. B.] MassGen Hosp Children, Med Genet Unit, Boston, MA USA. [Deutsch, C. K.] Eunice Kennedy Shriver Ctr Mental Retardat Inc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 397 EP 397 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800072 ER PT J AU Toufaily, MH Westgate, MN Holmes, LB AF Toufaily, M. H. Westgate, M-N Holmes, L. B. TI Triploidy: Variations in Phenotype SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Toufaily, M. H.; Westgate, M-N; Holmes, L. B.] MassGen Hosp Children, Boston, MA USA. [Toufaily, M. H.; Westgate, M-N; Holmes, L. B.] Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 420 EP 420 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800116 ER PT J AU Rezende, FA Qian, CX Sapieha, P AF Rezende, Flavio A. Qian, Cynthia X. Sapieha, Przemyslaw TI Evaluation of the vitreous microbial contamination rate in office-based three-port microincision vitrectomy surgery using Retrector technology SO BMC OPHTHALMOLOGY LA English DT Article ID PARS-PLANA VITRECTOMY; RETINAL VEIN OCCLUSION; 25-GAUGE VITRECTOMY; BACTERIAL-CONTAMINATION; DIAGNOSTIC DILEMMAS; CATARACT-SURGERY; ANTERIOR-CHAMBER; POVIDONE-IODINE; ENDOPHTHALMITIS; 20-GAUGE AB Background: To perform a microbiological contamination analysis of the vitreous during office-based micro-incision vitrectomy surgery (MIVS) assessing whether the bacteria detected correlated with patient's ocular conjunctival flora. Methods: This is a prospective, interventional, nonrandomized case series of patients undergoing office-based MIVS, anti-VEGF, and dexamethasone intravitreal injections (triple therapy) for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME). All patients were operated at a small procedure room in an ambulatory clinic of the Department of Ophthalmology, University of Montreal, Quebec, Canada. Conjunctival samples were done before placing the sclerotomies. The MIVS was done with a 23-gauge retractable vitrector, a 27-gauge infusion line, and a 29-gauge chandelier. Undiluted and diluted vitreous were collected for aerobic, anaerobic and fungal cultures. Outcomes measured were bacterial species identification within samples collected from the conjunctiva and the vitreous. Results: Thirty-seven patients (37 eyes) were recruited and completed over 17 months of follow-up. Twenty-eight had wet AMD and nine had DME. There were 13 men and 24 women, with a mean age of 78 years. Eighteen patients (46%) had culture positive conjunctival flora. Twenty-six bacterial colonies were tabulated in total from the conjunctival swabs. All bacteria detected were gram-positive bacteria (100%), most commonly: Staphylococcus epidermitis in 11 (42%) and Corynebacterium sp. in 6 (23%). Only 1/18 patients had more than 3 species isolated, 6/18 patients had 2 species and 11/18 patients had 1 species identified on the conjunctival swab. Only 1 of the 37 undiluted midvitreous samples was culture positive, equating to a contamination rate of 2.7%. None of the diluted vitreous samples were culture positive. All cultures were negative for fungus. No serious postoperative complications occurred, including bacterial endophthalmitis, choroidal detachment, and retinal detachment. Conclusion: This preliminary study of office-based MIVS gives us insights on the ocular surface microbial profile and vitreous contamination rate of performing such procedures outside the OR-controlled environment. Our initial results seem to indicate that there is little risk of bacterial translocation and contamination from the conjunctiva into the vitreous. Therefore, if endophthalmitis occurs post-operatively, the source may likely arise after the procedure. Larger studies are needed to confirm our data. C1 [Rezende, Flavio A.; Qian, Cynthia X.; Sapieha, Przemyslaw] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada. [Rezende, Flavio A.] Pontificia Univ Catolica Rio de Janeiro, Dept Ophthalmol, Rio De Janeiro, Brazil. [Qian, Cynthia X.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. [Rezende, Flavio A.] Hop Maison Neuve Rosemont, Dept Ophthalmol, Montreal, PQ H1T 2M4, Canada. RP Rezende, FA (reprint author), Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada. EM frezendef@hotmail.com FU Fonds de Recherche en Ophtalmologie de l'Universite de Montreal (FROUM); University of Montreal, (Montreal, Quebec, Canada); Retina Foundation of Canada; Novartis Canada; Retina Foundation of Canada clinical research grant; Alcon Research Institute New Investigator Award; Canadian Institute of Health Research (CIHR); Canadian National Institute for the Blind (CNIB); Canadian Diabetes Association FX Supported in part by a research grant from the Fonds de Recherche en Ophtalmologie de l'Universite de Montreal (FROUM), University of Montreal, (Montreal, Quebec, Canada), a research grant from Retina Foundation of Canada (clinical research grant to Dr. Rezende); and an instrument grant from Novartis Canada. The sponsors or funding organizations had no role in the design or conduct of this research. The authors report no financial conflict of interest. Dr. Rezende received a Retina Foundation of Canada clinical research grant. Dr. Sapieha is an Alcon Research Institute New Investigator Award recipient and has operating grants from the Canadian Institute of Health Research (CIHR), the Canadian National Institute for the Blind (CNIB), and the Canadian Diabetes Association. NR 31 TC 1 Z9 1 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD MAY 1 PY 2014 VL 14 AR 58 DI 10.1186/1471-2415-14-58 PG 7 WC Ophthalmology SC Ophthalmology GA AH5MO UT WOS:000336174400001 PM 24886149 ER PT J AU Faquin, WC AF Faquin, William C. TI Use of conventional smears versus liquid-based preparations for fine-needle aspirate specimens: The time has not come to abandon your conventional smears! SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID INTERLABORATORY COMPARISON PROGRAM; CYTOLOGY; PITFALLS; BIOPSY; GLAND C1 [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org NR 17 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2014 VL 122 IS 5 BP 340 EP 342 DI 10.1002/cncy.21407 PG 3 WC Oncology; Pathology SC Oncology; Pathology GA AG9DL UT WOS:000335718800006 PM 24591441 ER PT J AU Ebi, H Faber, AC Engelman, JA Yano, S AF Ebi, Hiromichi Faber, Anthony C. Engelman, Jeffrey A. Yano, Seiji TI Not just gRASping at flaws: Finding vulnerabilities to develop novel therapies for treating KRAS mutant cancers SO CANCER SCIENCE LA English DT Review DE Apoptosis; Kirsten rat-sarcoma; MEK; phosphatidylinositol 3-kinase; synthetic lethality ID CELL LUNG-CANCER; SYNTHETIC LETHAL INTERACTION; ONCOGENIC KRAS; RAL GTPASES; AZD6244 ARRY-142886; COLORECTAL CANCERS; MEK1/2 INHIBITOR; BREAST-CANCER; PI3 KINASE; ACTIVATION AB Mutations in Kirsten rat-sarcoma (KRAS) are well appreciated to be major drivers of human cancers through dysregulation of multiple growth and survival pathways. Similar to many other non-kinase oncogenes and tumor suppressors, efforts to directly target KRAS pharmaceutically have not yet materialized. As a result, there is broad interest in an alternative approach to develop therapies that induce synthetic lethality in cancers with mutant KRAS, therefore exposing the particular vulnerabilities of these cancers. Fueling these efforts is our increased understanding into the biology driving KRAS mutant cancers, in particular the important pathways that mutant KRAS governs to promote survival. In this mini-review, we summarize the latest approaches to treat KRAS mutant cancers and the rationale behind them. C1 [Ebi, Hiromichi; Yano, Seiji] Kanazawa Univ, Canc Res Inst, Div Med Oncol, Kanazawa, Ishikawa 9200934, Japan. [Faber, Anthony C.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Faber, Anthony C.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. RP Ebi, H (reprint author), Kanazawa Univ, Canc Res Inst, Div Med Oncol, 13-1 Takaramachi, Kanazawa, Ishikawa 9200934, Japan. EM hebi@staff.kanazawa-u.ac.jp OI Ebi, Hiromichi/0000-0003-3155-7576 NR 63 TC 7 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 EI 1349-7006 J9 CANCER SCI JI Cancer Sci. PD MAY PY 2014 VL 105 IS 5 BP 499 EP 505 DI 10.1111/cas.12383 PG 7 WC Oncology SC Oncology GA AH0RP UT WOS:000335828300001 PM 24612015 ER PT J AU Kuchimaru, T Hoshino, T Aikawa, T Yasuda, H Kobayashi, T Kadonosono, T Kizaka-Kondoh, S AF Kuchimaru, Takahiro Hoshino, Takuya Aikawa, Tomoya Yasuda, Hisataka Kobayashi, Tatsuya Kadonosono, Tetsuya Kizaka-Kondoh, Shinae TI Bone resorption facilitates osteoblastic bone metastatic colonization by cooperation of insulin-like growth factor and hypoxia SO CANCER SCIENCE LA English DT Article DE Bone resorption; hypoxia; IGF; IGFR signal; multimodality in vivo imaging; osteoblastic bone metastasis ID BREAST-CANCER CELLS; PROSTATE-CANCER; MULTIPLE-MYELOMA; TUMOR-GROWTH; EXPRESSION; HIF-1; RISK; OSTEOCLASTOGENESIS; CROSSTALK; SURVIVAL AB Bone metastasis is a multistep process that includes cancer cell dissemination, colonization, and metastatic growth. Furthermore, this process involves complex, reciprocal interactions between cancer cells and the bone microenvironment. Bone resorption is known to be involved in both osteolytic and osteoblastic bone metastasis. However, the precise roles of the bone resorption in the multistep process of osteoblastic bone metastasis remain unidentified. In this study, we show that bone resorption plays important roles in cancer cell colonization during the initial stage of osteoblastic bone metastasis. We applied bioluminescence/X-ray computed tomography multimodal imaging that allows us to spatiotemporally analyze metastasized cancer cells and bone status in osteoblastic bone metastasis models. We found that treatment with receptor activator of factor-B ligand (RANKL) increased osteoblastic bone metastasis when given at the same time as intracardiac injection of cancer cells, but failed to increase metastasis when given 4days after cancer cell injection, suggesting that RANKL-induced bone resorption facilitates growth of cancer cells colonized in the bone. We show that insulin-like growth factor-1 released from the bone during bone resorption and hypoxia-inducible factor activity in cancer cells cooperatively promoted survival and proliferation of cancer cells in bone marrow. These results suggest a mechanism that bone resorption and hypoxic stress in the bone microenvironment cooperatively play an important role in establishing osteoblastic metastasis. C1 [Kuchimaru, Takahiro; Hoshino, Takuya; Aikawa, Tomoya; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Tokyo 152, Japan. [Yasuda, Hisataka] Oriental Yeast Co Ltd, Planning & Dev Bioind Div, Tokyo, Japan. [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. RP Kizaka-Kondoh, S (reprint author), 4259-B-60 Nagatsuda Cho,Midori Ku, Yokohama, Kanagawa 2268501, Japan. EM skondoh@bio.titech.ac.jp RI Kuchimaru, Takahiro/B-9269-2015; Kondoh, Shinae/C-6937-2015 OI Kuchimaru, Takahiro/0000-0002-5355-3165; Kondoh, Shinae/0000-0003-3085-5782 FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Mitsubishi Foundation; Japan Society for the Promotion of Science (JSPS) FX Ministry of Education, Culture, Sports, Science and Technology of Japan. Mitsubishi Foundation. Japan Society for the Promotion of Science (JSPS) Fellows. NR 36 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1349-7006 J9 CANCER SCI JI Cancer Sci. PD MAY PY 2014 VL 105 IS 5 BP 553 EP 559 DI 10.1111/cas.12391 PG 7 WC Oncology SC Oncology GA AH0RP UT WOS:000335828300008 PM 24597654 ER PT J AU Kornides, ML Nansel, TR Quick, V Haynie, DL Lipsky, LM Laffel, LMB Mehta, SN AF Kornides, M. L. Nansel, T. R. Quick, V. Haynie, D. L. Lipsky, L. M. Laffel, L. M. B. Mehta, S. N. TI Associations of family meal frequency with family meal habits and meal preparation characteristics among families of youth with type 1 diabetes SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE adolescents; diabetes; family meals; nutrition ID CHOICE COPING STRATEGIES; DIET QUALITY; EMPLOYED PARENTS; ADOLESCENTS; PATTERNS; CHILDREN; DINNER; FOOD; VALIDATION; BEHAVIORS AB BackgroundWhile benefits of family mealtimes, such as improved dietary quality and increased family communication, have been well-documented in the general population, less is known about family meal habits that contribute to more frequent family meals in youth with type 1 diabetes. MethodsThis cross-sectional study surveyed 282 youth ages 8-18 years with type 1 diabetes and their parents on measures regarding diabetes-related and dietary behaviours. T-tests determined significant differences in youth's diet quality, adherence to diabetes management and glycaemic control between those with and without regular family meals (defined as 5 meals per week). Logistic regression analyses determined unadjusted and adjusted associations of age, socio-demographics, family meal habits, and family meal preparation characteristics with regular family meals. Results57% of parents reported having regular family meals. Families with regular family meals had significantly better diet quality as measured by the Healthy Eating Index (P < 0.05) and the NRF9.3 (P < 0.01), and adherence to diabetes management (P < 0.001); the difference in glycaemic control approached statistical significance (P = 0.06). Priority placed on, pleasant atmosphere and greater structure around family meals were each associated with regular family meals (P < 0.05). Meals prepared at home were positively associated with regular family meals, while convenience and fast foods were negatively associated (P < 0.05). Families in which at least one parent worked part-time or stayed at home were significantly more likely to have regular family meals than families in which both parents worked full-time (P < 0.05). In the multivariate logistic regression model, greater parental priority given to family mealtimes (P < 0.001) and more home-prepared meals (P < 0.001) predicted occurrence of regular family meals; adjusting for parent work status and other family meal habits. ConclusionsStrategies for promoting families meals should not only highlight the benefits of family meals, but also facilitate parents' skills for and barriers to home-prepared meals. C1 [Kornides, M. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nansel, T. R.; Quick, V.; Haynie, D. L.; Lipsky, L. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Laffel, L. M. B.; Mehta, S. N.] Harvard Univ, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Joslin Diabet Ctr,Med Sch, Boston, MA 02115 USA. RP Kornides, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM melanie.kornides@mail.harvard.edu RI Kornides, Melanie/N-5862-2016; OI Haynie, Denise/0000-0002-8270-6079; Kornides, Melanie/0000-0003-1900-4530; Quick, Virginia/0000-0002-4338-963X; Nansel, Tonja/0000-0002-8298-7595 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Developmen [HHSN267200703434C]; National Institute of Child Health and Human Development, National Institutes of Health [T32HD060454] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN267200703434C.; Melanie Kornides was supported by Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. NR 25 TC 3 Z9 3 U1 5 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0305-1862 EI 1365-2214 J9 CHILD CARE HLTH DEV JI Child Care Health Dev. PD MAY PY 2014 VL 40 IS 3 BP 405 EP 411 DI 10.1111/cch.12078 PG 7 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA AE8WI UT WOS:000334283300013 PM 23731337 ER PT J AU Cavender, MA Rassi, AN Schwamm, LH Fonarow, GC Cannon, CP Peacock, WF Laskey, WK Hernandez, AF Peterson, ED Cox, M Grau-Sepulveda, M Bhatt, DL AF Cavender, Matthew A. Rassi, Andrew N. Schwamm, Lee H. Fonarow, Gregg C. Cannon, Christopher P. Peacock, W. Frank Laskey, Warren K. Hernandez, Adrian F. Peterson, Eric D. Cox, Margueritte Grau-Sepulveda, Marie Bhatt, Deepak L. TI Authors' Reply SO CLINICAL CARDIOLOGY LA English DT Letter C1 [Cavender, Matthew A.] Brigham & Womens Hosp, Heart & Vasc Ctr, TIMI Study Grp, Boston, MA 02115 USA. [Cavender, Matthew A.; Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Rassi, Andrew N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Dept Med, Los Angeles, CA USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Clin Res Inst, Boston, MA USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Hernandez, Adrian F.; Peterson, Eric D.; Cox, Margueritte; Grau-Sepulveda, Marie] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Heart & Vasc Ctr, Boston, MA 02115 USA. RP Cavender, MA (reprint author), Brigham & Womens Hosp, Heart & Vasc Ctr, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. OI Schwamm, Lee/0000-0003-0592-9145; Fuh, Jong-Ling/0000-0001-9135-3351 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 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 2014 VL 37 IS 5 BP 323 EP 323 DI 10.1002/clc.22265 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH0IK UT WOS:000335802400010 PM 24596074 ER PT J AU Urban, T Lim, R Merker, VL Muzikansky, A Harris, GJ Kassarjian, A Bredella, MA Plotkin, SR AF Urban, Trinity Lim, Ruth Merker, Vanessa L. Muzikansky, Alona Harris, Gordon J. Kassarjian, Ara Bredella, Miriam A. Plotkin, Scott R. TI Anatomic and Metabolic Evaluation of Peripheral Nerve Sheath Tumors in Patients With Neurofibromatosis 1 Using Whole-Body MRI and F-18\-FDG PET Fusion SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE neurofibromatosis 1; neurofibroma; malignant peripheral nerve sheath tumor; PET; malignancy ID POSITRON-EMISSION-TOMOGRAPHY; PLEXIFORM NEUROFIBROMA; DIAGNOSTIC EVALUATION; F-18-FDG PET/CT; TYPE-1; BENIGN; NF1; PROGRESSION; PET/MRI; LESION AB Purpose Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death for patients with neurofibromatosis type 1 (NF1). Identification of hypermetabolic lesions on PET may help identify patients at risk for MPNST. The objective of this study was to identify clinical and MRI-derived variables that predicted increased metabolic activity of neurofibromas in NF1 patients as determined by PET. Methods This prospective study included NF1 patients with neurofibromas of 5 cm in diameter or greater. All patients underwent whole-body MRI and F-18-FDG PET imaging. Tumor volume was calculated from the MR scans using a semiautomated 3-dimensional segmentation method. SUVmax's were calculated to quantify metabolic activity. Logistic regression analyses were performed to determine the relationship among SUVmax, tumor volume, location (extremity vs trunk), type (plexiform vs circumscribed), depth (superficial vs deep), patient age, and whole-body tumor burden. Results A total of 311 neurofibromas were identified in 19 NF1 patients (mean age, 38 years; range, 19-58 years). One extreme outlier was excluded from analysis. Whole-body tumor volumes ranged from 0.4 to 1182.4 mL. Fifty of 310 tumors were FDG-avid on PET (16%) with median SUVmax of 2.2 (range, 0.4-9.6). Metabolic activity (SUVmax >2.5) correlated with tumor location (deep > superficial, trunk > extremity) in tumors with PET avidity. Conclusions In NF1 patients with neurofibromas of 5 cm or greater, the majority of internal tumors are not metabolically active on PET. Tumors with increased metabolic activity as defined by SUVmax greater than 2.5 (ie, suggestive of MPNST) are more likely to be deep and located within the trunk. C1 [Urban, Trinity; Lim, Ruth; Harris, Gordon J.; Kassarjian, Ara; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Kassarjian, Ara] Corades SL, Madrid, Spain. RP Plotkin, SR (reprint author), Yawkey Ctr Outpatient Care, Dept Neurol, 55 Fruit St,YAW 9E, Boston, MA 02114 USA. EM splotkin@partners.org OI Merker, Vanessa/0000-0002-4542-5227 FU Department of Defense Neurofibromatosis Research Program [NF0502020]; Neurofibromatosis, Inc; Children's Tumor Foundation FX This work was supported by grants from the Department of Defense Neurofibromatosis Research Program (NF0502020); Neurofibromatosis, Inc; and Children's Tumor Foundation. NR 32 TC 7 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD MAY PY 2014 VL 39 IS 5 BP E301 EP E307 DI 10.1097/RLU.0b013e3182a757d3 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AF3KK UT WOS:000334610900002 PM 24152623 ER PT J AU Uneyama, H Takeuchi, K Tache, YF AF Uneyama, Hisayuki Takeuchi, Koji Tache, Yvette F. TI Molecular Basis of Gastrointestinal Chemical Senses SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material DE Taste; gut nutrient-sensing; gastrointestinal diseases ID GUT C1 [Uneyama, Hisayuki] Ajinomoto Co Inc, Inst Innovat, Frontier Res Labs, Umami Wellness Res Grp, Kawasaki, Kanagawa 2108681, Japan. [Takeuchi, Koji] Kyoto Pharmaceut Univ, Dept Pharmacol & Expt Therapeut, Div Pathol Sci, Yamashina Ku, Kyoto 6078414, Japan. [Tache, Yvette F.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Tache, Yvette F.] Univ Calif Los Angeles, Ctr Neurobiol Stress, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Digest Dis Div, Los Angeles, CA 90024 USA. [Tache, Yvette F.] VA Greater Los Angeles Healght Care Syst, Los Angeles, CA USA. RP Uneyama, H (reprint author), Ajinomoto Co Inc, Inst Innovat, Frontier Res Labs, Umami Wellness Res Grp, 1-1 Suzuki Cho, Kawasaki, Kanagawa 2108681, Japan. EM hisayuki_uneyama@ajinomoto.com NR 21 TC 0 Z9 0 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2014 VL 20 IS 16 BP 2667 EP 2668 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5NB UT WOS:000336175700001 PM 24828701 ER PT J AU Tache, Y Adelson, D Yang, H AF Tache, Yvette Adelson, David Yang, Hong TI TRH/TRH-R1 Receptor Signaling in the Brain Medulla as a Pathway of Vagally Mediated Gut Responses During the Cephalic Phase SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Dorsal vagal complex; enteric nervous system; gastric secretion; TRH; sham feeding and vagus ID THYROTROPIN-RELEASING-HORMONE; GASTRIC-ACID-SECRETION; DORSAL MOTOR NUCLEUS; RAPHE PALLIDUS NEURONS; CENTRAL-NERVOUS-SYSTEM; SUBSTANCE-P; NUTRITIONAL IMPLICATIONS; INTRACISTERNAL TRH; STABILIZED ANALOG; MYENTERIC NEURONS AB Pavlov's seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the cephalic phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response triggered by the cephalic phase. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr David Geffen Sch, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Ctr Neurobiol Stress,Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE DDRC, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIHDDK [DK 33061]; Center (Animal Core) [DK 41301] FX The authors' work was supported by the NIHDDK grant DK 33061, the Center grant DK 41301 (Animal Core), VA Merit Award and VA Research Career Scientist Award. We thank Eugenia Hu for helping in the preparation of to the manuscript. NR 102 TC 7 Z9 7 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2014 VL 20 IS 16 BP 2725 EP 2730 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5NB UT WOS:000336175700007 PM 23886382 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Yasutada Kaunitz, Jonathan D. TI Duodenal Luminal Chemosensing; Acid, ATP, and Nutrients SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Luminal nutrient; G-protein coupled receptors and gut hormone release ID PROTEIN-COUPLED RECEPTOR; DIPEPTIDYL-PEPTIDASE-IV; GLUCAGON-LIKE PEPTIDE-2; BICARBONATE SECRETION; RAT DUODENUM; GASTROINTESTINAL-TRACT; TASTE RECEPTORS; HCO3-SECRETION; CARBONIC-ANHYDRASES; CALCIUM-ABSORPTION AB Intestinal chemosensing of endogenous and exogenous luminal compounds, including acid, CO2, bile acids and nutrients is an emerging area of gastrointestinal research, since gut hormones, particularly including incretins and glucagon-like peptide-2 (GLP-2) are released in response to luminal nutrients. Identification of luminal chemosensors such as nutrient-ligand G-protein coupled receptors (GPCRs) in enteroendocrine cells has linked luminal compounds to the corresponding gut hormone release. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We have been studying the mechanisms by which luminal compounds are sensed via mucosal acid sensors and GPCRs, which trigger mucosal defense mechanisms. In addition to luminal acid/CO2 sensing in the duodenum, recent studies also show that compounds present post-prandially such as amino acids, bile acids and fatty acids, enhance duodenal mucosal defenses, with digestion following the initial gastric processing. These studies may form the basis for therapies in which luminal nutrients release gut hormones that affect the mucosal protection, appetite, satiety, and systemic metabolisms. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Vet Affairs Greater Los Angles Healthcare Syst, Los Angeles, CA 90073 USA. Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. RP Akiba, Y (reprint author), West Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU Ajinomoto Inc., Japan; AstraZeneca [IRUSESOM0424]; Department of Veterans Affairs Merit Review Award; NIH-NIDDK [R01 DK54221] FX Supported by a research grant from Ajinomoto Inc., Japan (Y. Akiba), Investigator-Sponsored Study Program of AstraZeneca IRUSESOM0424 (Y. Akiba), Department of Veterans Affairs Merit Review Award (J. Kaunitz), and NIH-NIDDK R01 DK54221 (J. Kaunitz). NR 65 TC 7 Z9 7 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2014 VL 20 IS 16 BP 2760 EP 2765 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5NB UT WOS:000336175700013 PM 23886391 ER PT J AU Goldfine, AB Patti, ME AF Goldfine, Allison B. Patti, Mary Elizabeth TI Diabetes Improvement Following Roux-en-Y Gastric Bypass: Understanding Dynamic Changes in Insulin Secretion and Action SO DIABETES LA English DT Editorial Material ID BARIATRIC SURGERY; GLUCOSE-METABOLISM; MEDICAL THERAPY; OBESE-PATIENTS; MELLITUS; HUMANS; TRIAL C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [R56-DK-036836, P30 DK036836, R56 DK095451, R56-DK-095451] NR 22 TC 6 Z9 6 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2014 VL 63 IS 5 BP 1454 EP 1456 DI 10.2337/db13-1918 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF6AK UT WOS:000334796600009 PM 24757197 ER PT J AU Wang, P Yoo, B Yang, JS Zhang, XL Ross, A Pantazopoulos, P Dai, GP Moore, A AF Wang, Ping Yoo, Byunghee Yang, Jingsheng Zhang, Xueli Ross, Alana Pantazopoulos, Pamela Dai, Guangping Moore, Anna TI GLP-1R-Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging SO DIABETES LA English DT Article ID IRON-OXIDE NANOPARTICLES; BETA-CELL MASS; PEPTIDE-1 RECEPTOR; GLP-1 RECEPTOR; TRANSPLANTED ISLETS; IMMUNE REJECTION; SIRNA DELIVERY; CONTRAST AGENT; EXENDIN-4; ENDOCYTOSIS AB Noninvasive assessment of pancreatic -cell mass would tremendously aid in managing type 1 diabetes (T1D). Toward this goal, we synthesized an exendin-4 conjugated magnetic iron oxide-based nanoparticle probe targeting glucagon-like peptide 1 receptor (GLP-1R), which is highly expressed on the surface of pancreatic -cells. In vitro studies in TC-6, the -cell line, showed specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared with nontargeted (termed MN-Cy5.5). In vivo magnetic resonance imaging showed a significant transverse relaxation time (T2) shortening in the pancreata of mice injected with the MN-Ex10-Cy5.5 probe compared with control animals injected with the nontargeted probe at 7.5 and 24 h after injection. Furthermore, T2 of the pancreata of prediabetic NOD mice was significantly higher than that of diabetic NOD mice after the injection of MN-Ex10-Cy5.5, indicating the decrease of probe accumulation in these animals due to -cell loss. Of note, T2 of prediabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly changed, reflecting the nonspecific mode of accumulation of nontargeted probe. We believe our results point to the potential for using this agent for monitoring the disease development and response of T1D to therapy. C1 [Wang, Ping; Yoo, Byunghee; Zhang, Xueli; Ross, Alana; Pantazopoulos, Pamela; Moore, Anna] Harvard Univ, Sch Med,Massachusetts Gen Hosp, Dept Radiol,Massachusetts Inst Technol, Mol Imaging Lab,Athinoula A Martinos Ctr Biomed I, Boston, MA 02115 USA. [Yang, Jingsheng; Dai, Guangping] Harvard Univ, Sch Med,Massachusetts Gen Hosp, Dept Radiol,Massachusetts Inst Technol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Zhang, Xueli] China Pharmaceut Univ, Sch Pharm, Ctr Drug Discovery, Nanjing, Jiangsu, Peoples R China. RP Moore, A (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Dept Radiol,Massachusetts Inst Technol, Mol Imaging Lab,Athinoula A Martinos Ctr Biomed I, Boston, MA 02115 USA. EM amoore@helix.mgh.harvard.edu OI Wang, Ping/0000-0001-6712-8939 FU JDRF [JDRF 37-2009-30]; Harvard/Massachusetts General Hospital Nuclear Medicine Training Program - U.S. Department of Energy [DE-SC0008430] FX This work was partly supported by a JDRF award (JDRF 37-2009-30) to A.M. and through the Harvard/Massachusetts General Hospital Nuclear Medicine Training Program funded by the U.S. Department of Energy (DE-SC0008430). NR 57 TC 11 Z9 11 U1 0 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2014 VL 63 IS 5 BP 1465 EP 1474 DI 10.2337/db13-1543 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF6AK UT WOS:000334796600013 PM 24458362 ER PT J AU Tabata, M Rodgers, JT Hall, JA Lee, Y Jedrychowski, MP Gygi, SP Puigserver, P AF Tabata, Mitsuhisa Rodgers, Joseph T. Hall, Jessica A. Lee, Yoonjin Jedrychowski, Mark P. Gygi, Steven P. Puigserver, Pere TI Cdc2-Like Kinase 2 Suppresses Hepatic Fatty Acid Oxidation and Ketogenesis Through Disruption of the PGC-1a and MED1 Complex SO DIABETES LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; YIN YANG 1; NONALCOHOLIC STEATOHEPATITIS; TRANSCRIPTIONAL REGULATION; MITOCHONDRIAL BIOGENESIS; COACTIVATOR PGC-1; SPLICING FACTORS; PROTEIN-KINASES; SKELETAL-MUSCLE; SR PROTEINS AB Hepatic ketogenesis plays an important role in catabolism of fatty acids during fasting along with dietary lipid overload, but the mechanisms regulating this process remain poorly understood. Here, we show that Cdc2-like kinase 2 (Clk2) suppresses fatty acid oxidation and ketone body production during diet-induced obesity. In lean mice, hepatic Clk2 protein is very low during fasting and strongly increased during feeding; however, in diet-induced obese mice, Clk2 protein remains elevated through both fed and fasted states. Liver-specific Clk2 knockout mice fed a high-fat diet exhibit increased fasting levels of blood ketone bodies, reduced respiratory exchange ratio, and increased gene expression of fatty acid oxidation and ketogenic pathways. This effect of Clk2 is cell-autonomous, because manipulation of Clk2 in hepatocytes controls genes and rates of fatty acid utilization. Clk2 phosphorylation of peroxisome proliferator-activated receptor coactivator (PGC-1) disrupts its interaction with Mediator subunit 1, which leads to a suppression of PGC-1 activation of peroxisome proliferator-activated receptor target genes in fatty acid oxidation and ketogenesis. These data demonstrate the importance of Clk2 in the regulation of fatty acid metabolism in vivo and suggest that inhibition of hepatic Clk2 could provide new therapies in the treatment of fatty liver disease. C1 [Tabata, Mitsuhisa; Rodgers, Joseph T.; Hall, Jessica A.; Lee, Yoonjin; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Tabata, Mitsuhisa; Rodgers, Joseph T.; Hall, Jessica A.; Lee, Yoonjin; Jedrychowski, Mark P.; Gygi, Steven P.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu FU American Heart Association; American Diabetes Association; Manpei Suzuki Diabetes Foundation; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [1-R01-DK-089883-01A1] FX M.T. was partly supported by postdoctoral fellowships from the American Heart Association, the American Diabetes Association, and the Manpei Suzuki Diabetes Foundation. J.A.H. was partly supported by a predoctoral fellowship from the American Heart Association. This work was supported by the American Diabetes Association and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases 1-R01-DK-089883-01A1. NR 43 TC 7 Z9 8 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2014 VL 63 IS 5 BP 1519 EP 1532 DI 10.2337/db13-1304 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF6AK UT WOS:000334796600017 PM 24458359 ER PT J AU Milan, D Singh, JP AF Milan, David Singh, Jagmeet P. TI Device implantation and complications: time to recalibrate our expectations? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID CARDIOVERTER-DEFIBRILLATOR; MYOCARDIAL-INFARCTION C1 [Milan, David; Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Cardiol Div,Heart Ctr, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. EM jsingh@partners.org NR 7 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2014 VL 35 IS 18 BP 1167 EP 1168 DI 10.1093/eurheartj/eht568 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH9RT UT WOS:000336480300006 PM 24482308 ER PT J AU Pier, DB Nunes, FP Plotkin, SR Stemmer-Rachamimov, AO Kim, JC Shih, HA Brastianos, P Lin, AE AF Pier, Danielle B. Nunes, Fabio P. Plotkin, Scott R. Stemmer-Rachamimov, Anat O. Kim, James C. Shih, Helen A. Brastianos, Priscilla Lin, Angela E. TI Turner syndrome and meningioma: Support for a possible increased risk of neoplasia in Turner syndrome SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Aortic dissection; Meningioma; NF2; Pseudocoarctation; Sex chromosome abnormality syndrome; Turner syndrome ID HORMONE REPLACEMENT THERAPY; NONMELANOMA SKIN-CANCER; MULTIPLE MENINGIOMAS; REPRODUCTIVE FACTORS; COHORT; WOMEN; TUMORS AB Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45, X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Pier, Danielle B.; Lin, Angela E.] MassGen Hosp Children, Med Genet Unit, Boston, MA USA. [Nunes, Fabio P.; Plotkin, Scott R.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.; Kim, James C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Brastianos, Priscilla] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Brastianos, Priscilla] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brastianos, Priscilla] Broad Inst MIT & Harvard, Boston, MA USA. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet Unit, CPZN-2222,185 Cambridge St, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu OI Pier, Danielle/0000-0001-8621-9131; Brastianos, Priscilla/0000-0003-4470-8425 NR 28 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 EI 1878-0849 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD MAY-JUN PY 2014 VL 57 IS 6 BP 269 EP 274 DI 10.1016/j.ejmg.2014.03.005 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AH8QE UT WOS:000336402300006 PM 24675142 ER PT J AU Chen, WL Walwyn, W Ennes, HS Kim, H McRoberts, JA Marvizon, JCG AF Chen, Wenling Walwyn, Wendy Ennes, Helena S. Kim, Hyeyoung McRoberts, James A. Marvizon, Juan Carlos G. TI BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE microglia; mouse; neurokinin 1 receptor; rat; substance P; trkB receptor ID RAT SPINAL-CORD; DORSAL-ROOT GANGLIA; SUBSTANCE-P RELEASE; PRIMARY SENSORY NEURONS; D-ASPARTATE RECEPTORS; SRC FAMILY KINASES; NEUROTROPHIC FACTOR; MEDIATED PHOSPHORYLATION; NEUROKININ-1 RECEPTOR; SYNAPTIC-TRANSMISSION AB NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substanceP release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was mediated by tropomyosin-related kinaseB (trkB) receptors and not p75 neurotrophin receptors (p75(NTR)), because it was not produced by proBDNF and was inhibited by the trkB antagonist ANA-12 but not by the p75(NTR) inhibitor TAT-Pep5. These effects are probably mediated through the truncated form of the trkB receptor as there is little expression of full-length trkB in dorsal root ganglion (DRG) neurons. Src family kinase inhibitors blocked the effect of BDNF, suggesting that trkB receptors promote the activation of these NMDA receptors by Src family kinase phosphorylation. Western blots of cultured DRG neurons revealed that BDNF increased Tyr(1472) phosphorylation of the NR2B subunit of the NMDA receptor, known to have a potentiating effect. Patch-clamp recordings showed that BDNF, but not proBDNF, increased NMDA receptor currents in cultured DRG neurons. NMDA-induced NK1R internalization was also enabled in a neuropathic pain model or by activating dorsal horn microglia with lipopolysaccharide. These effects were decreased by a BDNF scavenger, a trkB receptor antagonist and a Src family kinase inhibitor, indicating that BDNF released by microglia potentiates NMDA receptors in primary afferents during neuropathic pain. C1 [Chen, Wenling; McRoberts, James A.; Marvizon, Juan Carlos G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Chen, Wenling; Ennes, Helena S.; Kim, Hyeyoung; McRoberts, James A.; Marvizon, Juan Carlos G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Walwyn, Wendy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. RP Marvizon, JCG (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu FU National Institute of Drug Abuse [R01-DA033059]; Rehabilitation Research & Development Service, Department of Veterans Affairs [1I01RX000378]; Division of Digestive Diseases at the David Geffen School of Medicine, UCLA; NIH [1S10RR028124] FX Supported by grant R01-DA033059 to J.C.M and J.A.M. from the National Institute of Drug Abuse, grant 1I01RX000378 to J.C.M. from the Rehabilitation Research & Development Service, Department of Veterans Affairs and research funds from the Division of Digestive Diseases at the David Geffen School of Medicine, UCLA. Mutant mice were provided by the UCLA Behavioral Core by under the direction of Michael Fanselow and supported by NIH grant 1S10RR028124. This study was done under the umbrella of the following UCLA institutes: Brain Research Institute, Center for the Study of Opioid Receptors and Drugs of Abuse, CURE: Digestive Diseases Research Center and the Oppenheimer Family Center for Neurobiology of Stress. The authors declare no competing financial interests. NR 83 TC 14 Z9 14 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2014 VL 39 IS 9 BP 1439 EP 1454 DI 10.1111/ejn.12516 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AG1ZP UT WOS:000335215000005 PM 24611998 ER PT J AU Rogers, HJ Vardiman, JW Anastasi, J Raca, G Savage, NM Cherry, AM Arber, D Moore, E Morrissette, JJD Bagg, A Liu, YC Mathew, S Orazi, A Lin, P Wang, SA Bueso-Ramos, CE Foucar, K Hasserjian, RP Tiu, RV Karafa, M Hsi, ED AF Rogers, Heesun J. Vardiman, James W. Anastasi, John Raca, Gordana Savage, Natasha M. Cherry, Athena M. Arber, Daniel Moore, Erika Morrissette, Jennifer J. D. Bagg, Adam Liu, Yen-Chun Mathew, Susan Orazi, Attilio Lin, Pei Wang, Sa A. Bueso-Ramos, Carlos E. Foucar, Kathryn Hasserjian, Robert P. Tiu, Ramon V. Karafa, Matthew Hsi, Eric D. TI Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study SO HAEMATOLOGICA LA English DT Article ID SCORING SYSTEM; CYTOGENETIC ABNORMALITIES; CLINICAL-FEATURES; EVI1 EXPRESSION; SELF-RENEWAL; REARRANGEMENTS; AML; PROGNOSIS; INV(3)(Q21Q26)/T(3/3)(Q21,Q26); THERAPY AB Acute myeloid leukemia and myelodysplastic syndrome with inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) have a poor prognosis. Indeed, the inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) has been recognized as a poor risk karyotype in the revised International Prognostic Scoring System. However, inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) is not among the cytogenetic abnormalities pathognomonic for diagnosis of acute myeloid leukemia irrespective of blast percentage in the 2008 WHO classification. This multicenter study evaluated the clinico-pathological features of acute myeloid leukemia/myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) and applied the revised International Prognostic Scoring System to myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3; 3)(q21; q26.2). A total of 103 inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) patients were reviewed and had a median bone marrow blast count of 4% in myelodysplastic syndrome (n=40) and 52% in acute myeloid leukemia (n=63) (P<0.001). Ninety-one percent of patients showed characteristic dysmegakaryopoiesis. There was no difference in overall survival between acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) (12.9 vs. 7.9 months; P=0.16). Eighty-three percent of patients died (median follow up 7.9 months). Complex karyotype, monosomal karyotype and dysgranulopoiesis (but not blast percentage) were independent poor prognostic factors in the entire cohort on multivariable analysis. The revised International Prognostic Scoring System better reflected overall survival of inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) than the International Prognostic Scoring System but did not fully reflect the generally dismal prognosis. Our data support consideration of myelodysplastic syndrome with inv(3)(q21q26.2)/t(3; 3)(q21; q26.2) as an acute myeloid leukemia with recurrent genetic abnormalities, irrespective of blast percentage. C1 [Rogers, Heesun J.; Hsi, Eric D.] Cleveland Clin, Robert J Tomsich Pathol & Lab Med Inst, Dept Clin Pathol, Cleveland, OH 44195 USA. [Vardiman, James W.; Anastasi, John] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Raca, Gordana] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Savage, Natasha M.; Cherry, Athena M.; Arber, Daniel] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Moore, Erika; Morrissette, Jennifer J. D.; Bagg, Adam] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Liu, Yen-Chun; Mathew, Susan; Orazi, Attilio] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. [Lin, Pei; Wang, Sa A.; Bueso-Ramos, Carlos E.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Foucar, Kathryn] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tiu, Ramon V.] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Cleveland, OH USA. [Karafa, Matthew] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA. RP Rogers, HJ (reprint author), Cleveland Clin, Robert J Tomsich Pathol & Lab Med Inst, Dept Clin Pathol, Cleveland, OH 44195 USA. EM rogersj5@ccf.org FU NCI NIH HHS [P30 CA016672] NR 38 TC 12 Z9 12 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2014 VL 99 IS 5 BP 821 EP 829 DI 10.3324/haematol.2013.096420 PG 9 WC Hematology SC Hematology GA AH6RD UT WOS:000336257500009 PM 24463215 ER PT J AU Murphy, JM McCarthy, AE Baer, L Zima, BT Jellinek, MS AF Murphy, J. Michael McCarthy, Alyssa E. Baer, Lee Zima, Bonnie T. Jellinek, Michael S. TI Alternative National Guidelines for Treating Attention and Depression Problems in Children: Comparison of Treatment Approaches and Prescribing Rates in the United Kingdom and United States SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE attention-deficit disorder with hyperactivity; child; depression; practice guidelines ID DEFICIT/HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDER; ADOLESCENTS; PREVALENCE; CHILDHOOD; CARE; PERSPECTIVE; IMPAIRMENT; DIAGNOSIS; UK AB The use of psychotropic medications for children and adolescents with attention and depression problems continues to generate both attention in the news media and controversy within the field. Given that the United Kingdom has recently issued guidelines for its national health service that differ substantially from those in the United States, the time is ripe to reexamine the evidence. The purpose of this article is to describe the UK's new "stepped care" guidelines for treating attention and depression problems in children and to compare them to the US guidelines issued by the American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry. Our findings are that, despite many similarities, the UK guidelines are generally more conservative in their recommendations for medication use, especially for children experiencing only moderate impairment. Our article also compares prescription and diagnosis rates in the UK and the US, and reports evidence for lower rates of prescribing in the UK, despite some evidence that the rates of problems may not differ substantially. We conclude by noting that the existence of an alternative standard provides validation for clinicians or families who prefer to take a more conservative approach to medication use. The two different approaches to care also provide a valuable opportunity for research to determine whether the approaches result in different treatment outcomes. C1 [Murphy, J. Michael; Baer, Lee; Jellinek, Michael S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jellinek, Michael S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Murphy, J. Michael; McCarthy, Alyssa E.; Baer, Lee; Jellinek, Michael S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Zima, Bonnie T.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Yawkey 6a, Boston, MA 02114 USA. EM mmurphy6@partners.org FU Foundation for Excellence in Mental Health Care FX Supported, in part, by a grant from the Foundation for Excellence in Mental Health Care (Drs. Murphy and Baer, and Ms. McCarthy). NR 47 TC 1 Z9 1 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2014 VL 22 IS 3 BP 179 EP 192 DI 10.1097/HRP.0000000000000026 PG 14 WC Psychiatry SC Psychiatry GA AH4EN UT WOS:000336079700004 PM 24736521 ER PT J AU Sheikh, HU Cho, TA AF Sheikh, Huma U. Cho, Tracey A. TI Clinical Aspects of Headache in HIV SO HEADACHE LA English DT Review DE HIV; headache; preventive; abortive; migraine; opportunistic ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY STANDARDS SUBCOMMITTEE; EPISODIC MIGRAINE; AMERICAN ACADEMY; INFECTION; GUIDELINES; ADULTS; PREVENTION; PREVALENCE; NEUROLOGY AB BackgroundHeadaches are commonly seen in those patients with human immunodeficiency virus (HIV) and are the most common form of pain reported among HIV patients. There have been relatively few studies attempting to determine the rates and phenotypes of the headaches that occur in patients with HIV. DiscussionPatients with HIV are susceptible to a much broader array of secondary headache causes, sometimes with atypical manifestations due to a dampened inflammatory response. The investigation of a headache in the HIV patient should be thorough and focused on making sure that secondary and HIV-specific causes are either ruled out or treated if present. ConclusionAn effective treatment plan should incorporate the use of appropriate pharmacological agents along with the integration of non-pharmacological therapies, such as relaxation and lifestyle regulation. When treating for headaches in patients with HIV, it is important to keep in mind comorbidities and other medications, especially combination antiretroviral therapy. For those with complicated headache histories, referral to a specialized headache center may be appropriate. C1 [Sheikh, Huma U.] Harvard Univ, Sch Med, Dept Neurol, John Graham Headache Ctr,Brigham & Womens Faulkne, Boston, MA 02115 USA. [Cho, Tracey A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurol Infect Dis Program, Boston, MA 02114 USA. RP Cho, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurol Infect Dis Program, 55 Fruit St, Boston, MA 02114 USA. NR 28 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD MAY PY 2014 VL 54 IS 5 BP 939 EP 945 DI 10.1111/head.12357 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AG8IW UT WOS:000335663000017 PM 24750042 ER PT J AU Joshi, SG Cho, TA AF Joshi, Shivang G. Cho, Tracey A. TI Clinical Aspects of Headache in HIV SO HEADACHE LA English DT Review DE opportunistic; preventive; abortive; HIV; migraine; headache ID VIRUS TYPE-1 INFECTION; COAT PROTEIN; NERVOUS-SYSTEM; DURA-MATER; IN-VITRO; IMMUNODEFICIENCY; BRAIN; RECEPTOR; NEUROTOXICITY; AIDS AB Background Headaches are commonly seen in those patients with human immunodeficiency virus (HIV) and are the most common form of pain reported among HIV patients. There have been relatively few studies attempting to determine the rates and phenotypes of the headaches that occur in patients with HIV. Discussion Patients with HIV are susceptible to a much broader array of secondary headache causes, sometimes with atypical manifestations due to a dampened inflammatory response. The investigation of a headache in the HIV patient should be thorough and focused on making sure that secondary and HIV-specific causes are either ruled out or treated if present. Conclusion An effective treatment plan should incorporate the use of appropriate pharmacological agents along with the integration of non-pharmacological therapies, such as relaxation and lifestyle regulation. When treating for headaches in patients with HIV, it is important to keep in mind comorbidities and other medications, especially combination antiretroviral therapy. For those with complicated headache histories, referral to a specialized headache center may be appropriate. C1 [Joshi, Shivang G.] Univ Massachusetts, Sch Med, Dept Neurol, New England Reg Headache Ctr, Worcester, MA 01655 USA. [Cho, Tracey A.] Harvard Univ, Sch Med, Dept Neurol, Neurol Infect Dis Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Cho, TA (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, New England Reg Headache Ctr, 85 Prescott St,Suite 101, Worcester, MA 01655 USA. NR 42 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 EI 1526-4610 J9 HEADACHE JI Headache PD MAY PY 2014 VL 54 IS 5 BP 946 EP 950 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AG8IW UT WOS:000335663000018 PM 24735239 ER PT J AU Hoge, EA Anderson, E Lawson, EA Bui, E Fischer, LE Khadge, SD Barrett, LF Simon, NM AF Hoge, Elizabeth A. Anderson, Eric Lawson, Elizabeth A. Bui, Eric Fischer, Laura E. Khadge, Shradha D. Barrett, Lisa Feldman Simon, Naomi M. TI Gender moderates the effect of oxytocin on social judgments SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE oxytocin; visual perception; affective learning; facial expression; social learning; neuropeptide ID INTRANASAL OXYTOCIN; MALE-RATS; HUMANS; FACES; EXPRESSION; ANXIETY AB ObjectiveThe neuropeptide oxytocin is implicated in social processing, and recent research has begun to explore how gender relates to the reported effects. This study examined the effects of oxytocin on social affective perception and learning. MethodsForty-seven male and female participants made judgments of faces during two different tasks, after being randomized to either double-blinded intranasal oxytocin or placebo. In the first task, unseen affective stimuli were presented in a continuous flash suppression paradigm, and participants evaluated faces paired with these stimuli on dimensions of competence, trustworthiness, and warmth. In the second task, participants learned affective associations between neutral faces and affective acts through a gossip learning procedure and later made affective ratings of the faces. ResultsIn both tasks, we found that gender moderated the effect of oxytocin, such that male participants in the oxytocin condition rated faces more negatively, compared with placebo. The opposite pattern of findings emerged for female participants: they rated faces more positively in the oxytocin condition, compared with placebo. ConclusionsThese findings contribute to a small but growing body of research demonstrating differential effects of oxytocin in men and women. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Hoge, Elizabeth A.; Bui, Eric; Fischer, Laura E.; Khadge, Shradha D.; Barrett, Lisa Feldman; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hoge, Elizabeth A.; Lawson, Elizabeth A.; Bui, Eric; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Eric; Khadge, Shradha D.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Lawson, Elizabeth A.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Bui, Eric] Univ Toulouse, Toulouse, France. [Bui, Eric] CHU Toulouse, Toulouse, France. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ehoge@partners.org RI Bui, Eric/J-8347-2015; Hoge, Elizabeth/H-5879-2012; OI Bui, Eric/0000-0002-1413-6473; Hoge, Elizabeth/0000-0002-5513-2292; Anderson, Eric/0000-0002-4215-6308 FU Highland Street Foundation; NIH [R01MH093394]; [DP1OD003312] FX The authors would like to thank everyone involved in this project, including Victoria Smith. The research was supported by the Highland Street Foundation (Hoge, Simon, and Fischer), by grant DP1OD003312 (Barrett), and NIH grant R01MH093394 (Simon). NR 30 TC 13 Z9 13 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6222 EI 1099-1077 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD MAY PY 2014 VL 29 IS 3 BP 299 EP 304 DI 10.1002/hup.2402 PG 6 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA AF2DP UT WOS:000334523100013 PM 24911580 ER PT J AU Sanfilippo, KM McTigue, KM Fidler, CJ Neaton, JD Chang, YF Fried, LF Liu, SM Kuller, LH AF Sanfilippo, Kristen M. McTigue, Kathleen M. Fidler, Christian J. Neaton, James D. Chang, Yuefang Fried, Linda F. Liu, Simin Kuller, Lewis H. TI Hypertension and Obesity and the Risk of Kidney Cancer in 2 Large Cohorts of US Men and Women SO HYPERTENSION LA English DT Article DE blood pressure; body weight; epidemiology; kidney neoplasms; obesity ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU GENE; BLOOD-PRESSURE; ANTIHYPERTENSIVE MEDICATION; POSTMENOPAUSAL WOMEN; LIPID-PEROXIDATION; CIGARETTE-SMOKING; UNITED-STATES; MECHANISMS; ASCERTAINMENT AB Kidney cancer incidence is increasing globally. Reasons for this rise are unclear but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity and kidney cancer incidence in 156 774 participants of the Women's Health Initiative clinical trials and observational studies over 10.8 years. In addition, we examined the effect of blood pressure (BP) on kidney cancer deaths for over 25 years among the 353 340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the Women's Health Initiative, systolic BP (SBP) was categorized in 6 groups from <120 to >160 mm Hg, and body mass index was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (P value for trend <0.0001) and body mass index categories (P value for trend <0.0001). In adjusted Cox proportional hazards models, both SBP levels and body mass index were predictors of kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer among the 353 340 participants aged 35 to 57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (hazard ratio, 1.87 for SBP>160 versus <120 mm Hg; 95% confidence interval, 1.38-2.53). Risk was increased among cigarette smokers. Further research is needed to determine the pathophysiologic basis of relationships between both higher BP and the risk of kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk. C1 [Sanfilippo, Kristen M.] Washington Univ, Dept Hematol, St Louis, MO USA. [Sanfilippo, Kristen M.] VA St Louis Healthcare Syst, Res Serv, St Louis, MO USA. [McTigue, Kathleen M.; Fried, Linda F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Chang, Yuefang] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [McTigue, Kathleen M.; Fried, Linda F.; Kuller, Lewis H.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Fidler, Christian J.] Abington Mem Hosp, Rosenfeld Canc Ctr, Abington, PA 19001 USA. [Neaton, James D.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Dept Peritoneal Dialysis, Pittsburgh, PA USA. [Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. RP McTigue, KM (reprint author), Univ Pittsburgh, Dept Med & Epidemiol, 230 McKee Pl Suite 600, Pittsburgh, PA 15213 USA. EM kmm34@pitt.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU Women's Health Initiative (WHI); National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; University of Pittsburgh Internal Medicine Residency program; NHLBI, NIH, Bethesda, MD; NIH/NHLBI [R01-HL-43232, R01-HL-68140] FX The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Dr Sanfilippo's time on this project was supported by the University of Pittsburgh Internal Medicine Residency program. The Multiple Risk Factor Intervention Trial was contracted by the NHLBI, NIH, Bethesda, MD. Followup after the end of the trial was supported with NIH/NHLBI grants -R01-HL-43232 and R01-HL-68140. NR 35 TC 9 Z9 10 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD MAY PY 2014 VL 63 IS 5 BP 934 EP 941 DI 10.1161/HYPERTENSIONAHA.113.02953 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AE9IG UT WOS:000334320900021 PM 24637660 ER PT J AU Ananthakrishnan, AN Nguyen, DD Sauk, J Yajnik, V Xavier, RJ AF Ananthakrishnan, Ashwin N. Nguyen, Deanna D. Sauk, Jenny Yajnik, Vijay Xavier, Ramnik J. TI Genetic Polymorphisms in Metabolizing Enzymes Modifying the Association Between Smoking and Inflammatory Bowel Diseases SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE ulcerative colitis; genetics; smoking; Crohn's disease ID GLUTATHIONE S-TRANSFERASES; CROHNS-DISEASE; ULCERATIVE-COLITIS; CIGARETTE-SMOKING; NICOTINE METABOLISM; CLINICAL-COURSE; OLMSTED COUNTY; HEAVY SMOKING; LUNG-CANCER; MOIST SNUFF AB Background: Cigarette smoking is a well-established environmental risk factor for Crohn's disease (CD) and ulcerative colitis (UC). The exact mechanism of its effect remains unexplained. Genetic polymorphisms in metabolizing enzymes may influence susceptibility to the effect of smoking and shed light on its mechanism of action. Methods: We used a prospective cohort of patients with CD, UC, and healthy controls. Smoking status was defined as current, former, or never smoking. Patients were genotyped for polymorphisms in CYP2A6, glutathione transferase enzymes (GSTP1 and GSTM1), NAD(P)H quinone oxidoreductase (NQO), and heme oxygenase 1 using a Sequenom platform. Multivariate logistic regression models with CD or UC as the outcome, stratified by genotype, were developed and interaction P-values calculated. Results: Our study included 634 patients with CD, 401 with UC, and 337 healthy controls. Ever smokers had an increased risk of CD (odds ratio = 3.88, 95% confidence interval = 2.35-6.39) compared with nonsmokers among patients with AG/AA genotypes at CYP2A6. However, ever smoking was not associated with CD among patients with the AA genotype (P-interaction = 0.001). Former smoking was associated with an increased risk for UC only in the presence of GG/AG genotypes for GSTP1 but not in those with the AA genotype (P-interaction = 0.012). Polymorphisms at the NQO and HMOX loci did not demonstrate a statistically significant interaction with smoking and risk of CD or UC. Conclusions: Genetic polymorphisms in metabolizing enzymes may influence the association between smoking and CD and UC. Further studies of gene-environment interaction in inflammatory bowel disease are warranted. C1 [Ananthakrishnan, Ashwin N.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Broad Inst, Cambridge, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health (NIH) [P30 DK043351, K23 DK097142, U01 DK062432, R01 DK064869]; American College of Gastroenterology FX Supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. A. N. Ananthakrishnan is supported in part by a grant from the NIH (K23 DK097142) and the American College of Gastroenterology. R. J. Xavier is supported by Grants U01 DK062432 and R01 DK064869 from the NIH. NR 43 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2014 VL 20 IS 5 BP 783 EP 789 DI 10.1097/MIB.0000000000000014 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH0CU UT WOS:000335787500003 PM 24651583 ER PT J AU Tran, HT Lee, IA Low, D Kamba, A Mizoguchi, A Shi, HN Lee, CG Elias, JA Mizoguchi, E AF Tran, Hoa T. Lee, In-Ah Low, Daren Kamba, Alan Mizoguchi, Atsushi Shi, Hai N. Lee, Chun G. Elias, Jack A. Mizoguchi, Emiko TI Chitinase 3-like 1 Synergistically Activates IL6-mediated STAT3 Phosphorylation in Intestinal Epithelial Cells in Murine Models of Infectious Colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE chitinase; STAT3; cytokine; intestinal epithelial cells ID INFLAMMATORY-BOWEL-DISEASE; INVASIVE ESCHERICHIA-COLI; CROHNS-DISEASE; SALMONELLA-TYPHIMURIUM; BACTERIAL ADHESION; MICE; HOST; REGRESSION; RESPONSES; PROTEIN AB Background: Chitinase 3-like 1 (CHI3L1) is an inducible molecule on intestinal epithelial cells during the development of inflammatory bowel disease. Methods: To investigate the role of CHI3L1 in bacterial infectious colitis, we orally inoculated pathogenic Salmonella typhimurium and potentially pathogenic adherent-invasive Escherichia coli (AIEC) LF82 virulent strain into C57Bl/6 wild-type mice or CHI3L1 knockout (KO) mice. Results: Both S. typhimurium and AIEC LF82 were found to efficiently induce severe intestinal inflammation in wild-type mice but not in CHI3L1 KO mice. These bacteria-infected CHI3L1 KO mice exhibit decreased cellular infiltration, bacterial translocation, and production of interleukin (IL)-6 and IL-22, as compared with those of wild-type mice. More importantly, CHI3L1 KO mice displayed aberrant STAT3 activation after bacterial infections. Co-stimulation of CHI3L1 and IL-6, but not IL-22, synergistically activates STAT3 signaling pathway in intestinal epithelial cells in an NF-kappa B/MAPK-dependent manner. Conclusions: CHI3L1 promotes the onset of selected gram-negative bacterial infectious colitis through IL-6/STAT3 pathway. C1 [Tran, Hoa T.; Lee, In-Ah; Low, Daren; Kamba, Alan; Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Atsushi; Shi, Hai N.] Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Mizoguchi, Atsushi; Mizoguchi, Emiko] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Boston, MA 02114 USA. [Shi, Hai N.] Massachusetts Gen Hosp, Dept Pediat, Div Mucosal Immunol, Boston, MA 02114 USA. [Mizoguchi, Emiko] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Chun G.; Elias, Jack A.] Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, New Haven, CT 06510 USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, GRJ 825D,55 Fruit St, Boston, MA 02114 USA. EM emizoguchi@mgh.harvard.edu FU National Institutes of Health [R01-DK80070]; Broad Medical Foundation; American Gastroenterological Association Foundation; A*STAR Graduate Academy (Singapore); I-A; National Research Foundation of Korea FX Supported by the National Institutes of Health (R01-DK80070) and grants from the Broad Medical Foundation and American Gastroenterological Association Foundation to E. Mizoguchi. D. Low has been awarded the fellowship grant supported by A*STAR Graduate Academy (Singapore), and I-A. Lee was supported by the National Research Foundation of Korea. NR 28 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2014 VL 20 IS 5 BP 835 EP 846 DI 10.1097/MIB.0000000000000033 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH0CU UT WOS:000335787500008 PM 24694795 ER PT J AU Martins, PNA Tullius, SG Markmann, JF AF Martins, Paulo Ney Aguiar Tullius, Stefan G. Markmann, James F. TI Immunosenescence and Immune Response in Organ Transplantation SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE aging; elderly; immunosenescence; transplantation ID AGE-RELATED-CHANGES; CELL TOLERANCE INDUCTION; HEAT-SHOCK RESPONSE; REGULATORY T-CELLS; DENDRITIC CELLS; RECIPIENT AGE; ANTIGEN-EXPRESSION; INNATE IMMUNITY; B-CELLS; IMMUNOLOGICAL-TOLERANCE AB The immune system undergoes a complex and continuous remodeling with aging. Immunosenescence results into both quantitative and qualitative changes of specific cellular subpopulations that have major impact on allorecognition and alloresponse, and consequently on graft rejection and tolerance. Here, we are going to review the immunological changes associated with the aging process relevant for transplantation. Interventions to selectively target changes associated with the senescence process seem promising therapeutic strategies to improve transplantation outcome. C1 [Martins, Paulo Ney Aguiar; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat,Dept Surg, Boston, MA 02114 USA. [Tullius, Stefan G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Transplantat,Dept Surg, Boston, MA 02114 USA. RP Martins, PNA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat,Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM Martins.Paulo@mgh.harvard.edu FU NIAID NIH HHS [R01 AI057851] NR 142 TC 5 Z9 6 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0883-0185 EI 1563-5244 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD MAY-JUN PY 2014 VL 33 IS 3 BP 162 EP 173 DI 10.3109/08830185.2013.829469 PG 12 WC Immunology SC Immunology GA AH9IO UT WOS:000336455500002 PM 24127845 ER PT J AU Nunes, MCP Handschumacher, MD Levine, RA Barbosa, MM Carvalho, VT Esteves, WA Zeng, X Guerrero, JL Zheng, H Tan, TC Hung, J AF Nunes, Maria Carmo P. Handschumacher, Mark D. Levine, Robert A. Barbosa, Marcia M. Carvalho, Vinicius T. Esteves, William A. Zeng, Xin Guerrero, J. Luis Zheng, Hui Tan, Timothy C. Hung, Judy TI Role of LA Shape in Predicting Embolic Cerebrovascular Events in Mitral Stenosis Mechanistic Insights From 3D Echocardiography SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE echocardiography; embolic events; left atrial function; left atrial shape; mitral stenosis ID SPONTANEOUS ECHO CONTRAST; LEFT ATRIAL VOLUME; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; SYSTEMIC EMBOLISM; VALVE DISEASE; SINUS RHYTHM; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CHAMBER QUANTIFICATION; FUTURE-DIRECTIONS; RISK PREDICTION AB OBJECTIVES This study was designed to assess the role of left atrial (LA) shape in predicting embolic cerebrovascular events (ECE) in patients with mitral stenosis (MS). BACKGROUND Patients with rheumatic MS are at increased risk for ECE. LA remodeling in response to MS involves not only chamber dilation but also changes in the shape. We hypothesized that a more spherical LA shape may be associated with increased embolic events due to predisposition to thrombus formation or to atrial arrhythmias compared with an elliptical-shaped LA of comparable volume. METHODS A total of 212 patients with MS and 20 control subjects were enrolled. LA volume, LA emptying fraction, and cross-sectional area were measured by 3-dimensional (3D) transthoracic echocardiography. LA shape was expressed as the ratio of measured LA end-systolic volume to hypothetical sphere volume ([4/ 3 pi r(3)] where r was obtained from 3D cross-sectional area). The lower the LA shape index, the more spherical the shape. RESULTS A total of 41 patients presented with ECE at the time of enrollment or during follow-up. On multivariate analysis, LA 3D emptying fraction (adjusted odds ratio [OR]: 0.96; 95% confidence interval [Cl]: 0.92 to 0.99; p = 0.028) and LA shape index (OR: 0.73; 95% Cl: 0.61 to 0.87; p < 0.001) emerged as important factors associated with ECE, after adjustment for age and anticoagulation therapy. In patients in sinus rhythm, LA shape index remained associated with ECE (OR: 0.79; 95% Cl: 0.67 to 0.94; p = 0.007), independent of age and LA function. An in vitro phantom atrial model demonstrated more stagnant flow profiles in spherical compared with ellipsoidal chamber. CONCLUSIONS In rheumatic MS patients, differential LA remodeling affects ECE risk. A more spherical LA shape was independently associated with an increased risk for ECE, adding incremental value in predicting events beyond that provided by age and LA function. (c) 2014 by the American College of Cardiology Foundation C1 [Nunes, Maria Carmo P.; Barbosa, Marcia M.; Carvalho, Vinicius T.; Esteves, William A.] Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG, Brazil. [Nunes, Maria Carmo P.; Handschumacher, Mark D.; Levine, Robert A.; Zeng, Xin; Tan, Timothy C.; Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Guerrero, J. Luis] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Lab, Boston, MA USA. [Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasilia, Brazil); National Institutes of Health/National Heart, Lung, and Blood Institute [R01 HL092101] FX This study was partly supported by grants from CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasilia, Brazil) and by the National Institutes of Health/National Heart, Lung, and Blood Institute grant no. R01 HL092101 (Dr. Hung). All authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 32 TC 3 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 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2014 VL 7 IS 5 BP 453 EP 461 DI 10.1016/j.jcmg.2014.01.013 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH5SY UT WOS:000336192600002 PM 24831206 ER PT J AU Shah, RV Heydari, B Coelho-Filho, O Abbasi, SA Feng, JH Neilan, TG Francis, S Blankstein, R Steigner, M Jerosch-Herold, M Kwong, RY AF Shah, Ravi V. Heydari, Bobak Coelho-Filho, Otavio Abbasi, Siddique A. Feng, Jiazhuo H. Neilan, Tomas G. Francis, Sanjeev Blankstein, Ron Steigner, Michael Jerosch-Herold, Michael Kwong, Raymond Y. TI Vasodilator Stress Perfusion CMR Imaging Is Feasible and Prognostic in Obese Patients SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; obesity; stress testing ID CARDIAC MAGNETIC-RESONANCE; CORONARY-ARTERY-DISEASE; EMISSION-COMPUTED-TOMOGRAPHY; BODY-MASS INDEX; MYOCARDIAL-INFARCTION; MR-IMPACT; MULTICENTER; PREVALENCE; TRIAL; RISK AB OBJECTIVES This study sought to determine feasibility and prognostic performance of stress cardiac magnetic resonance (CMR) in obese patients (body mass index [BMI] >= kg/m(2)). BACKGROUND Current stress imaging methods remain limited in obese patients. Given the impact of the obesity epidemic on cardiovascular disease, alternative methods to effectively risk stratify obese patients are needed. METHODS Consecutive patients with a BMI >= 30 kg/m(2) referred for vasodilating stress CMR were followed for major adverse cardiovascular events (MACE), defined as cardiac death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic association of inducible ischemia or late gadolinium enhancement (LGE) by CMR beyond traditional clinical risk indexes. RESULTS Of 285 obese patients, 272 (95%) completed the CMR protocol, and among these, 255 (94%) achieved diagnostic imaging quality. Mean BMI was 35.4 +/- 4.8 kg/m(2), with a maximum weight of 200 kg. Reasons for failure to complete CMR included claustrophobia (n = 4), intolerance to stress agent (n = 4), poor gating (n = 4), and declining participation (n = 1). Sedation was required in 19 patients (7%; 2 patients with intravenous sedation). Sixteen patients required scanning by a 70-cm bore system (6%). Patients without inducible ischemia or LGE experienced a substantially lower annual rate of MACE (0.3% vs. 6.3% for those with ischemia and 6.7% for those with ischennia and LGE). Median follow-up of the cohort was 2.1 years. In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, inducible ischemia (hazard ratio 7.5; 95% confidence interval: 2.0 to 28.0; p = 0.002) remained independently associated with MACE. When patients with early coronary revascularization (within 90 days of CMR) were censored on the day of revascularization, both presence of inducible ischemia and ischemia extent per segment maintained a strong association with MACE. CONCLUSIONS Stress CMR is feasible and effective in prognosticating obese patients, with a very low negative event rate in patients without ischemia or infarction. (c) 2014 by the American College of Cardiology Foundation C1 [Shah, Ravi V.; Heydari, Bobak; Abbasi, Siddique A.; Feng, Jiazhuo H.; Neilan, Tomas G.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,Noninvas Cardiovasc Imagi, Boston, MA 02115 USA. [Shah, Ravi V.; Heydari, Bobak; Abbasi, Siddique A.; Feng, Jiazhuo H.; Neilan, Tomas G.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shah, Ravi V.; Neilan, Tomas G.; Francis, Sanjeev] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Coelho-Filho, Otavio] Univ Estadual Campinas, Div Cardiol, Campinas, SP, Brazil. RP Kwong, RY (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM rykwong@partners.org OI Abbasi, Siddique/0000-0002-9601-7565 FU American Heart Association Post-Doctoral Fellowship Award [11POST000002]; Heart Failure National Institutes of Health Clinical Research Network [U01-HL084877]; Clinical Fellowship Award from the Alberta Heritage Foundation for Medical Research; National Institutes of Health grant [RO1-HL091157]; Astellas Pharma US FX Dr. Shah is supported by an American Heart Association Post-Doctoral Fellowship Award (11POST000002) and a training grant from the Heart Failure National Institutes of Health Clinical Research Network (U01-HL084877). Dr. Heydari is supported by a Clinical Fellowship Award from the Alberta Heritage Foundation for Medical Research. Dr. Kwong is supported by National Institutes of Health grant RO1-HL091157. Dr. Kwong receives research support from Astellas Pharma US. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Shah and Heydari contributed equally to this work. NR 27 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2014 VL 7 IS 5 BP 462 EP 472 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH5SY UT WOS:000336192600003 PM 24726254 ER PT J AU Jansen, K Mani, N Mehrotra, P Tan, TC Zeng, X Dinwoodey, D Picard, MH Hung, J AF Jansen, Katrijn Mani, Navin Mehrotra, Praveen Tan, Timothy C. Zeng, Xin Dinwoodey, Danya Picard, Michael H. Hung, Judy TI Left Atrial Volumes Should We Reset the Reference Standard? SO JACC-CARDIOVASCULAR IMAGING LA English DT Letter C1 [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 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 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2014 VL 7 IS 5 BP 530 EP 531 DI 10.1016/j.jcmg.2013.09.024 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH5SY UT WOS:000336192600014 PM 24831215 ER PT J AU Hanson, L VandeVusse, L Duster, M Warrack, S Safdar, N AF Hanson, Lisa VandeVusse, Leona Duster, Megan Warrack, Simone Safdar, Nasia TI Feasibility of Oral Prenatal Probiotics against Maternal Group B Streptococcus Vaginal and Rectal Colonization SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE pregnancy; probiotics; group B Streptococcus ID PATIENT PREFERENCE; ANTIBIOTICS; INFECTIONS; WOMEN; RISK; LACTOBACILLI; PROPHYLAXIS; EXPOSURE; EFFICACY; OUTCOMES AB ObjectiveTo examine the effect of an oral prenatal probiotic on group B Streptococcus (GBS) colonization and to demonstrate the feasibility of a larger randomized controlled trial. DesignThis pilot study was an open-label, two-group quasi-experiment. SettingAn urban central city nurse-midwifery and wellness center serving a diverse population. ParticipantsTen pregnant participants received the oral probiotic (Florajen3) taken once daily, and 10 participants served as controls. MethodsA questionnaire on dietary practices, vaginal cleansing, sexual history, and symptoms and GBS colony count samples were taken at 28-, 32-, and 36-weeks gestation. ResultsParticipants in the probiotic group reported no adverse events or minor side effects; one half reported improved gastrointestinal symptoms. Although two women in each group had positive qualitative prenatal GBS cultures at 36weeks, the probiotic group participants had lower quantitative GBS colony counts. The eight GBS negative averaged 90% probiotic adherence compared with two GBS positive women who averaged 68%. Yogurt ingestion was inversely related (p=.02) to GBS colonization. ConclusionsPrenatal probiotic therapy has the potential to reduce GBS colonization. The potential of the probiotic intervention appears to be linked to daily adherence. A controlled clinical trial with a larger, adequately powered sample is feasible and justified. C1 [Hanson, Lisa; VandeVusse, Leona] Marquette Univ, Coll Nursing, Nurse Midwifery Program, Milwaukee, WI 53201 USA. [Hanson, Lisa] Aurora Sinai Midwifery & Wellness Ctr, Milwaukee, WI USA. [Duster, Megan] Univ Wisconsin, Sch Med & Publ Hlth, Infect Dis Res Lab, Div Infect Dis, Madison, WI USA. [Warrack, Simone] Univ Wisconsin, Sch Med & Publ Hlth, Infect Dis Res Lab, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med & Infect Dis, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Hanson, L (reprint author), Marquette Univ, Coll Nursing, Clark Hall 341,POB 1881, Milwaukee, WI 53201 USA. EM lisa.hanson@mu.edu FU American Lifeline Inc. FX Funded by an unrestricted research grant from American Lifeline Inc. NR 37 TC 7 Z9 7 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-2175 EI 1552-6909 J9 JOGNN-J OBST GYN NEO JI JOGNN PD MAY PY 2014 VL 43 IS 3 BP 294 EP 304 DI 10.1111/1552-6909.12308 PG 11 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA AH0SB UT WOS:000335829500007 PM 24754328 ER PT J AU Stefan, M Zhang, WJ Concepcion, E Yi, ZZ Tomer, Y AF Stefan, Mihaela Zhang, Weijia Concepcion, Erlinda Yi, Zhengzi Tomer, Yaron TI DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Type I diabetes; DNA methylation; Monozygotic twins; Transcriptional regulation ID RHEUMATOID-ARTHRITIS; MELLITUS; PROMOTER AB Type 1 diabetes (T1D) shows similar to 40% concordance rate in monozygotic twins (MZ) suggesting a role for environmental factors and/or epigenetic modifications in the etiology of the disease. The aim of our study was to dissect the contribution of epigenetic factors, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell lines from 3 monozygotic (MZ) twin pairs discordant for T1D and 6 MZ twin pairs concordant for the disease using HumanMethylation27 BeadChip. This assay assesses the methylation state of 27,578 CpG sites, mostly located within proximal promoter regions. We identified 88 CpG sites displaying significant methylation changes in all T1D-discordant MZ twin pairs. Functional annotation of the genes with distinct CpG methylation profiles in T1D samples showed differential DNAm of immune response and defense response pathways between affected and unaffected twins. Integration of DNAm data with GWAS data mapped several known T1D associated genes, HLA, INS, IL-2RB, CD226, which showed significant differences in DNAm between affected and unaffected of twins. Our findings suggest that abnormalities of DNA methylation patterns, known to regulate gene transcription, may be involved in the pathogenesis of TI D. Published by Elsevier Ltd. C1 [Stefan, Mihaela; Concepcion, Erlinda; Tomer, Yaron] Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA. [Zhang, Weijia; Yi, Zhengzi] Mt Sinai Sch Med, Dept Med, Bioinformat Core, New York, NY 10029 USA. [Stefan, Mihaela; Tomer, Yaron] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Div Endocrinol, Box 1055,One Gustave L Levy Pl, New York, NY 10029 USA. EM Yaron.Tomer@mssm.edu FU NIDDK [DK061659, DK067555 82, DK073681]; Department of Veterans Affairs,Veterans Health Administration, Office of Research and Development; VA Biomedical Laboratory Research and Development Merit Award [1I01BX002031] FX We thank the National Disease Research Interchange (NDRI, Philadelphia, PA) for providing us with the DNA samples of the diabetes twins. This work was supported in part by grants DK061659, DK067555 82 DK073681 from NIDDK (to YT). In addition this material is based upon 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 1I01BX002031 (to YT). NR 22 TC 35 Z9 39 U1 2 U2 21 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2014 VL 50 BP 33 EP 37 DI 10.1016/j.jaut.2013.10.001 PG 5 WC Immunology SC Immunology GA AH4RB UT WOS:000336114600004 PM 24210274 ER PT J AU Joseph, CS Patel, R Neel, VA Giles, RH Yaroslavsky, AN AF Joseph, Cecil S. Patel, Rakesh Neel, Victor A. Giles, Robert H. Yaroslavsky, Anna N. TI Imaging of ex vivo nonmelanoma skin cancers in the optical and terahertz spectral regions SO JOURNAL OF BIOPHOTONICS LA English DT Article DE optical imaging; terahertz imaging; polarization; nonmelanoma skin cancer ID BASAL-CELL CARCINOMA; POLARIZED-LIGHT; IN-VIVO; TISSUE; SPECTROSCOPY; MICROSCOPY; DIAGNOSIS; MELANOMA; MARGINS; RANGE AB We tested the hypothesis that polarization sensitive optical and terahertz imaging may be combined for accurate nonmelanoma skin cancer (NMSC) delineation. Nine NMSC specimens were imaged. 513 m and 440 nm wavelengths were used for terahertz and optical imaging, respectively. Histopathology was processed for evaluation. Terahertz reflectance of NMSC was quantified. Our results demonstrate that cross-polarized terahertz images correctly identified location of the tumours, whereas cross-polarized and polarization difference optical images accurately presented morphological features. Cross-polarized terahertz images exhibited lower reflectivity values in cancer as compared to normal tissue. Combination of optical and terahertz imaging shows promise for intraoperative delineation of NMSC ((c) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) C1 [Joseph, Cecil S.; Giles, Robert H.] Univ Massachusetts Lowell, Submillimeter Wave Technol Lab, Lowell, MA USA. [Patel, Rakesh; Yaroslavsky, Anna N.] Univ Massachusetts Lowell, Adv Biophoton Lab, Lowell, MA 01854 USA. [Neel, Victor A.; Yaroslavsky, Anna N.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Yaroslavsky, AN (reprint author), Univ Massachusetts Lowell, Adv Biophoton Lab, Lowell, MA 01854 USA. EM Anna_Yaroslavsky@uml.edu NR 36 TC 11 Z9 12 U1 4 U2 36 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD MAY PY 2014 VL 7 IS 5 BP 295 EP 303 DI 10.1002/jbio.201200111 PG 9 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA AG7ON UT WOS:000335607600003 PM 22987857 ER PT J AU Schneider, JC Mathews, K Ryan, CM AF Schneider, Jeffrey C. Mathews, Katie Ryan, Colleen M. TI Burn Rehabilitation Outcomes: Lessons Learned From the Uniform Data System for Medical Rehabilitation SO JOURNAL OF BURN CARE & RESEARCH LA English DT Editorial Material ID INJURY C1 [Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Schneider, Jeffrey C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schneider, Jeffrey C.; Ryan, Colleen M.] Harvard Univ, Sch Med, Boston, MA USA. [Schneider, Jeffrey C.; Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. [Mathews, Katie] Spaulding Rehabil Hosp, Boston, MA USA. [Ryan, Colleen M.] Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Boston, MA 02114 USA. RP Schneider, JC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2014 VL 35 IS 3 BP 212 EP 213 DI 10.1097/BCR.0b013e318299d505 PG 2 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AG4MS UT WOS:000335394600010 PM 23799485 ER PT J AU Liu, YM Ibrahim, A Jan, T Chang, P Fagan, S Goverman, J AF Liu, Yuk Ming Ibrahim, Amir Jan, Taha Chang, Phillip Fagan, Shawn Goverman, Jeremy TI Skin Necrosis as a Complication of Therapeutic Hypothermia SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CARDIAC-ARREST AB This case report describes a complication caused by cooling pads used for therapeutic hypothermic resuscitation. The authors hope to highlight and emphasize the importance of a thorough evaluation of all skin surfaces that are in direct contact with such cooling pads. Skin injury from the cooling pads used for therapeutic hypothermia should be recognized as a potential complication of treatment. C1 [Liu, Yuk Ming] Waterbury Hosp & Hlth Ctr, Dept Surg, Waterbury, CT USA. [Ibrahim, Amir; Jan, Taha; Chang, Phillip; Fagan, Shawn; Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Div Burns, Boston, MA 02114 USA. RP Goverman, J (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Burns, GR B-13-1302,55 Fruit St, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2014 VL 35 IS 3 BP E184 EP E186 DI 10.1097/BCR.0b013e3182a22730 PG 3 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AG4MS UT WOS:000335394600008 PM 24043239 ER PT J AU Todoran, TM Basile, JN Zile, MR AF Todoran, Thomas M. Basile, Jan N. Zile, Michael R. TI Renal Sympathetic Denervation for Blood Pressure Control: A Review of the Current Evidence and Ongoing Studies SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID DRUG-RESISTANT HYPERTENSION; AMERICAN-HEART-ASSOCIATION; GLOBAL SYMPLICITY REGISTRY; ARTERY DENERVATION; NERVOUS-SYSTEM; TRIAL; CATHETER; ULTRASOUND; RATIONALE; STATEMENT AB Few randomized trials have compared visit-to-visit variability (VVV) of systolic blood pressure (SBP) across drug classes. The authors compared VVV of SBP among 24,004 participants randomized to chlorthalidone, amlodipine, or lisinopril in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). VVV of SBP was calculated across 5 to 7 visits occurring 6 to 28months following randomization. The standard deviation (SD) of SBP was 10.6 (SD=5.0), 10.5 (SD=4.9), and 12.2 (SD=5.8) for participants randomized to chlorthalidone, amlodipine, and lisinopril, respectively. After multivariable adjustment including mean SBP across visits and compared with participants randomized to chlorthalidone, participants randomized to amlodipine had a 0.36 (standard error [SE]: 0.07) lower SD of SBP and participants randomized to lisinopril had a 0.77 (SE=0.08) higher SD of SBP. Results were consistent using other VVV of SBP metrics. These data suggest chlorthalidone and amlodipine are associated with lower VVV of SBP than lisinopril. C1 [Todoran, Thomas M.; Basile, Jan N.; Zile, Michael R.] Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. [Todoran, Thomas M.; Basile, Jan N.; Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Todoran, TM (reprint author), 25 Courtenay Dr MSC 592, Charleston, SC 29425 USA. EM todoran@musc.edu NR 33 TC 4 Z9 4 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD MAY PY 2014 VL 16 IS 5 BP 331 EP 341 DI 10.1111/jch.12290 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AH0IL UT WOS:000335802500004 PM 24655555 ER PT J AU Breu, AC Allen-Dicker, J Mueller, S Palamara, K Hinami, K Herzig, SJ AF Breu, Anthony C. Allen-Dicker, Joshua Mueller, Stephanie Palamara, Kerri Hinami, Keiki Herzig, Shoshana J. TI Hospitalist and Primary Care Physician Perspectives on Medication Management of Chronic Conditions for Hospitalized Patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID MULTIPLE CHRONIC CONDITIONS; LENGTH-OF-STAY; UNITED-STATES; READMISSION; PREVALENCE; QUALITY; SYSTEM AB BACKGROUNDLittle is currently known regarding physicians' opinions on the relative appropriateness of inpatient management of medical conditions unrelated to the reason for admission. OBJECTIVEInvestigate physician attitudes on the appropriateness of inpatient medication interventions, based on the interventions' relatedness to the reason for admission. DESIGN, SETTING, AND PARTICIPANTSCase-based survey of hospitalists and hospital-based primary care physicians at 3 academic medical centers in Boston, Massachusetts. METHODSPhysicians were emailed a survey consisting of 6 pairs of clinical cases. Each pair included 1 case with an inpatient management decision related to the reason for admission, followed by a case involving the same management decision but unrelated to the reason for admission. Respondents rated the appropriateness of the interventions, and results were compared based on the relatedness to the reason for admission and based on the respondents' primary role. RESULTSOverall, 162 out of 295 providers (55%) responded to the survey. Physicians were significantly more likely to rate inpatient interventions as appropriate when they were related, compared to unrelated, to the reason for admission (78.9% vs 38.8%; P<0.001). Primary care physicians were significantly more likely than hospitalists to feel that inpatient interventions were appropriate. (64.1% vs 52.1%, P<0.001; relative risk: 1.3, 95% confidence interval: 1.1-1.4). CONCLUSIONPhysicians are more likely to rate inpatient medication changes as appropriate when they are related to the reason for admission. Our results suggest that opportunities for meaningful medical interventions may be underutilized in current systems that adhere to a strict dichotomy of inpatient and outpatient roles. Journal of Hospital Medicine 2014;9:303-309. (c) 2013 Society of Hospital Medicine C1 [Breu, Anthony C.; Hinami, Keiki] NW Mem Hosp, Div Hosp Med, Chicago, IL 60611 USA. [Breu, Anthony C.; Hinami, Keiki] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Allen-Dicker, Joshua] Mt Sinai Med Ctr, Div Hosp Med, New York, NY 10029 USA. [Mueller, Stephanie] Brigham & Womens Hosp, Hospitalist Serv, Boston, MA 02115 USA. [Mueller, Stephanie] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Mueller, Stephanie; Palamara, Kerri; Herzig, Shoshana J.] Harvard Univ, Sch Med, Boston, MA USA. [Palamara, Kerri] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Herzig, Shoshana J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Breu, AC (reprint author), VA Boston Healthcare Syst, Med Serv 111, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM anthony.breu@va.gov OI Allen-Dicker, Joshua/0000-0003-3831-1050 FU National Institute on Aging [K23 AG042459] FX Dr. Herzig is supported by a grant from the National Institute on Aging (K23 AG042459). Dr. Herzig had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Author contributions: study concept and design, Breu, Allen-Dicker, Mueller, Herzig; acquisition of data, Breu, Allen-Dicker, Mueller, Palamara, Herzig; analysis and interpretation of data, Breu, Allen-Dicker, Hinami, Herzig; drafting of the manuscript, Breu; critical revision of the manuscript for important intellectual content, Breu, Allen-Dicker, Mueller, Palamara, Hinami, Herzig; statistical analysis, Allen-Dicker, Hinami, Herzig; study supervision, Breu, Herzig. This study was presented as a poster at the Society of Hospital Medicine National Meeting, Washington, DC, May 17, 2013. NR 16 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD MAY PY 2014 VL 9 IS 5 BP 303 EP 309 DI 10.1002/jhm.2137 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AG8JI UT WOS:000335664200005 PM 24616183 ER PT J AU Eng, JA Steinman, MA AF Eng, Jessica A. Steinman, Michael A. TI Changing Chronic Medications in Hospitalized Patients-Bridging the Inpatient-Outpatient Divide SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID DECISION-MAKING; DISCHARGE C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Eng, Jessica A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Eng, JA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,181G, San Francisco, CA 94121 USA. EM jessica.eng@ucsf.edu FU NIA NIH HHS [P30 AG044281, 1K23-AG030999, K23 AG030999] 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 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD MAY PY 2014 VL 9 IS 5 BP 332 EP 333 DI 10.1002/jhm.2172 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AG8JI UT WOS:000335664200011 PM 24616285 ER PT J AU Porhomayon, J Nader, ND Leissner, KB El-Solh, AA AF Porhomayon, Jahan Nader, Nader D. Leissner, Kay B. El-Solh, Ali A. TI Respiratory Perioperative Management of Patients With Obstructive Sleep Apnea SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article DE obstructive sleep apnea; positive pressure ventilation; obesity; complications; respiratory ID POSTOPERATIVE COMPLICATIONS; CLINICAL-PREDICTION; RECURRENT HYPOXEMIA; SURGICAL-PATIENTS; INTENSIVE-CARE; SCREENING TOOL; OBESE-PATIENTS; RISK-FACTORS; NASAL CPAP; SURGERY AB Obstructive sleep apnea (OSA) has become a major public health problem in the United State and Europe. However, perioperative strategies regarding diagnostic options and management of untreated OSA remain inadequate. Preoperative screening and identification of patients with undiagnosed OSA may lead to early perioperative interventions that may alter cardiopulmonary events associated with surgery and anesthesia.(1) Hence, clinicians need to become familiar with the preoperative screening and diagnosis of OSA. Perioperative management of a patient with OSA should be modified and may include regional anesthesia and alternative analgesic techniques such as nonsteroidal anti-inflammatory drugs that may reduce the need for systemic opioids. Additionally, supplemental oxygen and continuous pulse oximetry monitoring should be utilized to maintain baseline oxygen saturation. Postoperatively patients should remain in a semi-upright position and positive pressure therapy should be used in patients with high-risk OSA. C1 [Porhomayon, Jahan] SUNY Buffalo, Sch Med & Biomed Sci, VA Western New York Healthcare Syst, Dept Anesthesiol,Div Crit Care Med Anesthesiol &, Buffalo, NY 14260 USA. [Nader, Nader D.] SUNY Buffalo, Sch Med & Biomed Sci, VA Western New York Healthcare Syst, Dept Anesthesiol Surg & Pathol,Div Cardiothorac A, Buffalo, NY 14260 USA. [Leissner, Kay B.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Div Anesthesia & Crit Care Med, West Roxbury, MA USA. [Leissner, Kay B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [El-Solh, Ali A.] SUNY Buffalo, Sch Med & Biomed Sci, VA Western New York Healthcare Syst, Dept Med,Div Pulm Crit Care & Sleep, Buffalo, NY 14260 USA. RP Porhomayon, J (reprint author), VA Med Ctr, Rm 203C,3495 Bailey Ave, Buffalo, NY 14215 USA. EM jahan.porhomayon@va.gov OI Nader, Nader/0000-0002-5744-7319 NR 90 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0885-0666 EI 1525-1489 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD MAY PY 2014 VL 29 IS 3 BP 145 EP 153 DI 10.1177/0885066612446411 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA AG1XS UT WOS:000335210100004 PM 22588375 ER PT J AU Dutcher, JP Neuberg, D Atkins, MB Tester, WJ Wadler, S Stewart, JA Chachoua, A Schuchter, LM AF Dutcher, Janice P. Neuberg, Donna Atkins, Michael B. Tester, William J. Wadler, Scott Stewart, James A. Chachoua, Abraham Schuchter, Lynn M. TI Report of a Phase I Evaluation of Dose and Schedule of Interleukin-1 Alpha and Cyclophosphamide in Patients with Advanced Tumors: An Eastern Cooperative Oncology Group Study (PX990) and Review of IL-1-Based Studies of Hematopoietic Reconstitution SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-1-ALPHA; LYMPHOCYTE-ACTIVATING FACTOR; ENDOTHELIAL-CELLS; MICE; IL-1; IMMUNOTHERAPY; INFLAMMATION; INDUCTION; CANCER; CHEMOTHERAPY AB Interleukin-1 (IL-1) is a cytokine critical to inflammation, immunological activation, response to infection, and bone marrow hematopoiesis. Cyclophosphamide downmodulates immune suppressor cells and is cytotoxic to a variety of tumors. A phase I trial of IL-1 and cyclophosphamide was conducted by the Eastern Cooperative Oncology Group. This study evaluated 3 dose levels and 3 schedules in patients with solid tumors. The goal was to evaluate the hematopoietic supportive care effect and possible antitumor effect. Toxicity was fever, chills, hypotension, nausea/emesis, hepatic, and neutropenia. Toxicity increased with dose increases of interleukin-1. Treatment at all dose levels resulted in significant increases in total white blood cell (WBC) counts above baseline. Nadir WBC and nadir absolute neutrophil counts were not significantly different by dose level of IL-1 or schedule of IL-1. Toxicity due to IL-1 at higher doses prohibited further evaluation of this agent for hematopoietic support, particularly in view of the activity and tolerability of more lineage-specific hematopoietic cytokines. Therapeutic interventions in the role of IL-1 in inflammatory conditions and cancer may be further informed by our definition of its clinical and biological effects in this evaluation of dose and schedule. C1 [Dutcher, Janice P.; Wadler, Scott] Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Atkins, Michael B.] Beth Israel Deaconess, Div Oncol, Boston, MA USA. [Tester, William J.] Albert Einstein Med Ctr, Div Oncol, Philadelphia, PA 19141 USA. [Stewart, James A.] Univ Wisconsin, Div Oncol, Madison, WI USA. [Chachoua, Abraham] NYU, Med Ctr, Div Oncol, New York, NY 10016 USA. [Schuchter, Lynn M.] Univ Penn, Div Oncol, Philadelphia, PA 19104 USA. RP Dutcher, JP (reprint author), Canc Res Fdn, 750 Kappock St, Bronx, NY 10463 USA. EM jpd4401@aol.com FU Public Health Service [CA23318, CA66636, CA21115, CA14958, CA80775, CA20176, CA15488]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA14958, CA80775, CA20176, and CA15488 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 40 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD MAY PY 2014 VL 34 IS 5 BP 376 EP 384 DI 10.1089/jir.2013.0010 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA AH9ZD UT WOS:000336504000008 PM 24433038 ER PT J AU Wittenberg, E Paczynski, M Wiese, H Jackendoff, R Kuperberg, G AF Wittenberg, Eva Paczynski, Martin Wiese, Heike Jackendoff, Ray Kuperberg, Gina TI The difference between "giving a rose" and "giving a kiss": Sustained neural activity to the light verb construction SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article DE Event-related potential; Sentence processing; Light verb constructions; Argument structure; Syntax-semantics interface; Sustained negativity ID EVENT-RELATED POTENTIALS; BRAIN POTENTIALS; LANGUAGE COMPREHENSION; THEMATIC RELATIONSHIPS; ASPECTUAL COERCION; ERP; SENTENCE; DISCOURSE; ANIMACY; CONTEXT AB We used event-related potentials (ERPs) to investigate the neurocognitive mechanisms associated with processing light verb constructions such as "give a kiss". These constructions consist of a semantically underspecified light verb ("give") and an event nominal that contributes most of the meaning and also activates an argument structure of its own ("kiss"). This creates a mismatch between the syntactic constituents and the semantic roles of a sentence. Native speakers read German verb-final sentences that contained light verb constructions (e.g., "Julius gave Anne a kiss"), non-light constructions (e.g., "Julius gave Anne a rose"), and semantically anomalous constructions (e.g., 'Julius gave Anne a conversation"). ERPs were measured at the critical verb, which appeared after all its arguments. Compared to non-light constructions, the light verb constructions evoked a widely distributed, frontally focused, sustained negative-going effect between 500 and 900 ms after verb onset. We interpret this effect as reflecting working memory costs associated with complex semantic processes that establish a shared argument structure in the light verb constructions. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wittenberg, Eva; Paczynski, Martin; Jackendoff, Ray; Kuperberg, Gina] Tufts Univ, Medford, MA 02155 USA. [Wittenberg, Eva; Wiese, Heike] Univ Potsdam, Potsdam, Germany. [Kuperberg, Gina] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wittenberg, E (reprint author), Tufts Univ, Ctr Cognit Studies, 11 Miner Hall, Medford, MA 02155 USA. EM eva.wittenberg@tufts.edu FU NIMH [R01 MH071635]; Brain and Behavior Research Foundation (NARSAD); Sidney Baer Trust; German Federal Ministry of Economics and Technology FX This work was supported by NIMH (R01 MH071635) and the Brain and Behavior Research Foundation (NARSAD, with the Sidney Baer Trust) to Gina R. Kuperberg, as well as by a "European Recovery Program" scholarship to Eva Wittenberg, provided by the German Federal Ministry of Economics and Technology. We also thank Claire Bonial for help with the English corpus data, the conference audiences at CUNY 2011, AMLaP 2011, and SPR 2011, Hugh Rabagliati, as well as three anonymous reviewers and the editor, Martin Pickering, for many helpful comments. NR 63 TC 6 Z9 6 U1 4 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X EI 1096-0821 J9 J MEM LANG JI J. Mem. Lang. PD MAY PY 2014 VL 73 BP 31 EP 42 DI 10.1016/j.jml.2014.02.002 PG 12 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA AH4PS UT WOS:000336111100003 PM 24910498 ER PT J AU Boruta, DM Fagotti, A Bradford, LS Escobar, PF Scambia, G Kushnir, CL Michener, CM Fader, AN AF Boruta, David M. Fagotti, Anna Bradford, Leslie S. Escobar, Pedro F. Scambia, Giovanni Kushnir, Christina L. Michener, Chad M. Fader, Amanda Nickles TI Laparoendoscopic Single-site Radical Hysterectomy With Pelvic Lymphadenectomy: Initial Multi-institutional Experience for Treatment of Invasive Cervical Cancer SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Cervical cancer; Laparoendoscopic single-site surgery; Radical hysterectomy ID SURGERY LESS; ENDOMETRIAL CANCER; LAPAROTOMY; LAPAROSCOPY; INSTITUTION; TRIAL AB Study Objective: To describe the feasibility, safety, and outcomes of women with stage I cervical cancer treated with laparoendoscopic single-site surgery radical hysterectomy (LESS-RH). Design: A retrospective descriptive study (Canadian Task Force classification III). Setting: Multiple academic teaching hospitals. Patients: Women with Federation Internationale de Gynecologie et d'Obstetrique FIGO stage IAI to IBI cervical cancer. Interventions: LESS-RH as the primary therapy for cervical cancer performed by a gynecologic oncologist with expertise in LESS. A multichannel, single-port access device; a flexible-tipped 5-mm laparoscope; and a multifunctional instrument were used in all cases. Clinicopathologic, surgical, and perioperative outcomes were analyzed. Measurements and Main Results: Twenty-two women were identified in whom a LESS-RH was attempted; 20(91%) successfully underwent the procedure, including 19 in whom pelvic lymphadenectomy (PLND) was completed. Of the 2 converted procedures, 1 patient underwent 2-port laparoscopy secondary to truncal obesity, and I patient underwent conversion to laparotomy secondary to external iliac vein laceration during PLND. The median age and body mass index were 46 years and 23.3 kg/m(2), respectively. The median number of pelvic lymph nodes removed was 22. One patient experienced an intraoperative complication, and no patient required reoperation. The margins of excision were negative. One patient with 2 positive pelvic nodes and 1 patient with microscopic parametrial disease received adjuvant chemosensitized radiation; 3 additional patients received adjuvant radiation therapy secondary to an intermediate risk for recurrence. After a median follow up of 11 months, no recurrences were detected. Conclusion: LESS-RH/PLND is feasible and safe for select patients with stage I cervical cancer. Larger studies are needed to confirm whether the increased technical difficulty of this procedure justifies its use in routine gynecologic oncology practice. (C) 2014 AAGL. All rights reserved. C1 [Boruta, David M.; Bradford, Leslie S.] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Fagotti, Anna] Univ Perugia, St Maria Hosp, Div Minimally Invas Gynecol, Terni, Italy. [Escobar, Pedro F.] HIMA San Pablo, Div Gynecol Oncol, Caguas, PR USA. [Escobar, Pedro F.; Michener, Chad M.] Cleveland Clin, Div Gynecol Oncol, Cleveland, OH 44106 USA. [Scambia, Giovanni] Univ Cattolica Sacro Cuore, Div Gynecol Oncol, I-00168 Rome, Italy. [Kushnir, Christina L.; Fader, Amanda Nickles] Johns Hopkins Univ Hosp, Div Gynecol Oncol, Baltimore, MD USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Vincent Obstet & Gynecol Serv, Gillette Ctr Gynecol Oncol, Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM dboruta@partners.org NR 35 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 EI 1553-4669 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD MAY-JUN PY 2014 VL 21 IS 3 BP 394 EP 398 DI 10.1016/j.jmig.2013.10.005 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH5SP UT WOS:000336191700014 PM 24161887 ER PT J AU Ginat, DT Schaefer, PW AF Ginat, Daniel Thomas Schaefer, Pamela W. TI Imaging guidelines and findings of extracranial glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Glioblastoma; Metastases; Extracranial; Imaging; Guidelines ID CEREBROSPINAL-FLUID DISSEMINATION; ACR APPROPRIATENESS CRITERIA(R); CERVICAL-SPINAL CORD; INTRACRANIAL GLIOBLASTOMA; CUTANEOUS METASTASIS; RECIST GUIDELINE; MULTIFORME; ASTROCYTOMAS; DISEASE; CANCER AB Extracranial manifestations of glioblastoma are uncommon and include a wide spectrum of entities, such as primary spinal cord glioblastoma, spinal leptomeningeal metastasis, seeding into the scalp following intracranial glioblastoma resection, direct extension of an intracranial glioblastoma though a craniotomy defect, dissemination via shunt catheter, and systemic metastasis, including lymphatic and hematogenous spread. Imaging plays an important role in the management of patients with extracranial glioblastomas and guidelines for the imaging evaluation of these lesions are reviewed. For example, MRI is the modality of choice for evaluating glioblastoma involving the scalp and spine. In particular, advanced imaging techniques such as MR spectroscopy, MR perfusion, diffusion-weighted imaging, and diffusion-tensor imaging can be useful for early detection and characterization of these lesions. CT and (18)FDG-PET are suitable modalities for evaluating systemic and CSF shunt-related metastases. C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Schaefer, Pamela W.] Massachusetts Gen Hosp & Massachusetts, Dept Radiol, Boston, MA USA. RP Ginat, DT (reprint author), Univ Chicago, Dept Radiol, 5841 S,Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com NR 46 TC 5 Z9 6 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2014 VL 118 IS 1 BP 9 EP 18 DI 10.1007/s11060-014-1404-7 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH8HC UT WOS:000336376700002 PM 24557958 ER PT J AU Han, XS Li, R Zhang, WB Yang, XH Wheeler, CG Friedman, GK Province, P Ding, Q You, ZY Fathallah-Shaykh, HM Gillespie, GY Zhao, XY King, PH Nabors, LB AF Han, Xiaosi Li, Rong Zhang, Wenbin Yang, Xiuhua Wheeler, Crystal G. Friedman, Gregory K. Province, Paula Ding, Qiang You, Zhiying Fathallah-Shaykh, Hassan M. Gillespie, G. Yancey Zhao, Xinyang King, Peter H. Nabors, L. Burt TI Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Diffuse astrocytoma; Anaplastic astrocytoma; Glioblastoma; PRMT5; ERK1/2 ID PROTEIN ARGININE METHYLTRANSFERASE; CANCER CELLS; GERM-CELLS; METHYLATION; ACTIVATION; HISTONE; DIFFERENTIATION; GLIOBLASTOMA; DIMETHYLARGININE; TRANSCRIPTION AB Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of omega-NG,N'G-symmetric dimethylarginine residues on histones as well as other proteins. These modifications play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth. C1 [Han, Xiaosi; Zhang, Wenbin; Yang, Xiuhua; Wheeler, Crystal G.; Province, Paula; Fathallah-Shaykh, Hassan M.; King, Peter H.; Nabors, L. Burt] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Han, Xiaosi; King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35295 USA. [Li, Rong] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Friedman, Gregory K.] Univ Alabama Birmingham, Dept Pediat, Div Hematol Oncol, Birmingham, AL 35294 USA. [Ding, Qiang] Univ Alabama Birmingham, Div Pulm Med, Dept Med, Birmingham, AL 35294 USA. [You, Zhiying] Univ Alabama Birmingham, Dept Prevent Med, Birmingham, AL 35294 USA. [Gillespie, G. Yancey] Univ Alabama Birmingham, Dept Neurosurg, Birmingham, AL 35294 USA. [Zhao, Xinyang] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. RP Han, XS (reprint author), Univ Alabama Birmingham, Dept Neurol, FOT 1020,1530 3rd Ave S, Birmingham, AL 35294 USA. EM xhan@uab.edu OI Friedman, Gregory/0000-0002-6653-7420; Zhao, Xinyang/0000-0001-6677-7072 FU NIH NCI [P30CA013148, P50CA097247, P20CA151129]; St. Baldrick's Foundation; VA Merit Review FX NIH NCI Grants P30CA013148 (UAB Comprehensive Cancer Center Core Support Grant); P50CA097247, P20CA151129 (G. Y. Gillespie); St. Baldrick's Foundation (G. K. Friedman); VA Merit Review (P. H. King). NR 42 TC 13 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2014 VL 118 IS 1 BP 61 EP 72 DI 10.1007/s11060-014-1419-0 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH8HC UT WOS:000336376700007 PM 24664369 ER PT J AU Reuter, M Gerstner, ER Rapalino, O Batchelor, TT Rosen, B Fischl, B AF Reuter, Martin Gerstner, Elizabeth R. Rapalino, Otto Batchelor, Tracy T. Rosen, Bruce Fischl, Bruce TI Impact of MRI head placement on glioma response assessment SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE High Grade Glioma; MRI head placement; RANO; Macdonald criteria; Reliability; Treatment assessment ID HIGH-GRADE GLIOMAS; CRITERIA; NEUROONCOLOGY AB Diagnosis of progressive disease or (partial) response during tumor treatment is based on manual size estimates of enhancing tumor area: an expert measures two perpendicular diameters of the enhancing tumor region in a single MRI slice with the largest enhancing area. This paper analyzes the reliability of the area measure with respect to head placement in the MRI scanner and compares it with 3D volume measures in a dataset of eight subjects (5-7 follow-up scans each) with high-grade glioma. We show that the manual area measure is highly sensitive to head position changes, with a root mean squared error of 22 %, compared to volume estimates with less than 5 % error. In our simulated study using the 2D manual measurements, the majority of subjects would have been incorrectly diagnosed with progressive disease without any true anatomical changes. These results highlight the urgent need for revised and more reliable response assessment criteria, for example, based on increased slice resolution, 3D volume analysis and percent change computation with respect to an average of patient specific longitudinal measurements instead of a single measurement to define progression or response. C1 [Reuter, Martin; Gerstner, Elizabeth R.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Reuter, Martin; Rapalino, Otto; Rosen, Bruce; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Reuter, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM mreuter@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU National Center for Research Resources [P41-RR14075, U24-RR021382, 1UL1-RR025758-01, 1S10-RR023401, 1S10-RR019307, 1S10-RR023043]; National Institute for Biomedical Imaging and Bioengineering [5P41-EB015896-15, R01-EB006758]; National Cancer Institute [5U01-CA154601-03, N01-CM-2008-00060C]; National Institute on Aging [AG022381, 5R01-AG008122-22]; National Center for Alternative Medicine [RC1-AT005728-01]; National Institute for Neurological Disorders and Stroke [R01-NS052585-01, 1R21-NS072652-01, 1R01-NS070963]; Merck; Ellison Medical Foundation (The Autism & Dyslexia Project); National Institute of Health Blueprint for Neuroscience Research [5U01-MH093765] FX Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, U24-RR021382, 1UL1-RR025758-01, 1S10-RR023401, 1S10-RR019307, 1S10-RR023043), the National Institute for Biomedical Imaging and Bioengineering (5P41-EB015896-15, R01-EB006758), the National Cancer Institute (5U01-CA154601-03, N01-CM-2008-00060C), the National Institute on Aging (AG022381, 5R01-AG008122-22), the National Center for Alternative Medicine (RC1-AT005728-01), the National Institute for Neurological Disorders and Stroke (R01-NS052585-01, 1R21-NS072652-01, 1R01-NS070963), Merck, the Ellison Medical Foundation (The Autism & Dyslexia Project) and by the National Institute of Health Blueprint for Neuroscience Research (5U01-MH093765 Human Connectome Project). NR 13 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2014 VL 118 IS 1 BP 123 EP 129 DI 10.1007/s11060-014-1403-8 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH8HC UT WOS:000336376700014 PM 24566765 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI The Commitment to Influential Nursing Administration Research SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB This department highlights nursing leaders who have demonstrated a commitment to nursing leadership in research, practice, policy, education and theory. This interview profiles Donna Sullivan Havens, PhD, RN, FAAN, professor, The University of North Carolina at Chapel Hill. C1 [Adams, Jeffrey M.] Ctr Innovat Care Delivery, Boston, MA USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM Jeff.adams@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2014 VL 44 IS 5 BP 254 EP 256 DI 10.1097/NNA.0000000000000063 PG 3 WC Nursing SC Nursing GA AG6YZ UT WOS:000335566300004 ER PT J AU Rodrigues, EG Smith, K Maule, AL Sjodin, A Li, Z Romanoff, L Kelsey, K Proctor, S McClean, MD AF Rodrigues, Ema G. Smith, Kristen Maule, Alexis L. Sjodin, Andreas Li, Zheng Romanoff, Lovisa Kelsey, Karl Proctor, Susan McClean, Michael D. TI Urinary Polycyclic Aromatic Hydrocarbon (OH-PAH) Metabolite Concentrations and the Effect of GST Polymorphisms Among US Air Force Personnel Exposed to Jet Fuel SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID GENETIC POLYMORPHISMS; INHALATION EXPOSURE; NAPHTHALENE; BIOMARKERS; 1-HYDROXYPYRENE; 2-NAPHTHOL; NAPHTHOLS; CYP1A1; CYP2E1; JP-8 AB Objective: To evaluate the association between inhalation exposure to jet propulsion fuel 8 (JP-8) and urinary metabolites among US Air Force (USAF) personnel, and investigate the role of glutathione S-transferase polymorphisms. Methods: Personal air samples were collected from 37 full-time USAF personnel during 4 consecutive workdays and analyzed for JP-8 constituents and total hydrocarbons. Pre- and postshift urine samples were collected each day and analyzed for polycyclic aromatic hydrocarbon urinary metabolites. Results: Work shift exposure to total hydrocarbons was significantly associated with postshift urinary 1-naphthol ( = 0.17; P = <0.0001), 2-naphthol ( = 0.09; P = 0.005), and 2-hydroxyfluorene concentrations ( = 0.08; P = 0.006), and a significant gene-environment interaction was observed with glutathione S-transferase mu-1. Conclusions: USAF personnel experience inhalation exposure to JP-8, which is associated with absorption of JP-8 constituents while performing typical job-related tasks, and in our data the glutathione S-transferase mu-1 polymorphism was associated with differential metabolism of naphthalene. C1 [Rodrigues, Ema G.; Smith, Kristen] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Maule, Alexis L.; Proctor, Susan; McClean, Michael D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Sjodin, Andreas; Li, Zheng; Romanoff, Lovisa] Ctr Dis Control & Prevent, Organ Analyt Toxicol Branch, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Kelsey, Karl] Brown Univ, Sch Med, Dept Epidemiol, Providence, RI 02912 USA. [Proctor, Susan] US Army, Mil Performance Div, Environm Med Res Inst, Natick, MA 01760 USA. [Proctor, Susan] VA Boston Healthcare Syst, Boston, MA USA. RP Rodrigues, EG (reprint author), 665 Huntington Ave,Bldg 1 Room 1404F, Boston, MA 02115 USA. EM emarod@hsph.harvard.edu RI Sjodin, Andreas/F-2464-2010; McClean, Michael/J-2934-2015 FU US Army Medical Research and Materiel Command Award [W81XWH-06-1-0105] FX This research project was funded by the US Army Medical Research and Materiel Command Award (W81XWH-06-1-0105; PI: SP Proctor) to the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. NR 24 TC 4 Z9 4 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2014 VL 56 IS 5 BP 465 EP 471 DI 10.1097/JOM.0000000000000142 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH1FZ UT WOS:000335866500003 PM 24806557 ER PT J AU Duan, ZF Shen, J Yang, XQ Yang, P Osaka, E Choy, E Cote, G Harmon, D Zhang, Y Nielsen, GP Spentzos, D Mankin, H Hornicek, F AF Duan, Zhenfeng Shen, Jacson Yang, Xiaoqian Yang, Pei Osaka, Eiji Choy, Edwin Cote, Gregory Harmon, David Zhang, Yu Nielsen, G. Petur Spentzos, Dimitrios Mankin, Henry Hornicek, Francis TI Prognostic Significance of miRNA-1(miR-1) Expression in Patients with Chordoma SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE chordoma; miR-1; Met; prognostic biomarker ID LUNG-CANCER; CELL-LINE; HUMAN OSTEOSARCOMA; DOWN-REGULATION; MIR-1; MET; PROLIFERATION; MICRORNA-1; TARGETS; MIRNA AB Reliable prognostic biomarkers for chordoma have not yet been established. Recent studies revealed that expression of miRNA-1 (miR-1) is frequently downregulated in several cancer types including chordoma. The goal of this follow-up study is to investigate the expression of miR-1 as a prognostic biomarker and further confirm the functional role of miR-1 in chordoma cell growth and proliferation. We determined the relative expression levels of miR-1 and Met in chordoma tissue samples and correlated those to clinical variables. The results showed that miR-1 was downregulated in 93.7% of chordoma tissues and expression was inversely correlated with Met expression. miR-1 expression levels also correlated with clinical prognosis. To characterize and confirm the functional role of miR-1 in the growth and proliferation of chordoma cells, miR-1 precursors were stably transfected into chordoma cell lines UCH-1 and CH-22. Cell Proliferation Assay and MTT were used to evaluate cell growth and proliferation. Restoring expression of miR-1 precursor decreased cell growth and proliferation in UCH-1 and CH-22 cells. These results indicate that suppressed miR-1 expression in chordoma may in part be a driver for tumor growth, and that miR-1 has potential to serve as prognostic biomarker and therapeutic target for chordoma patients. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:695-701, 2014. C1 [Duan, Zhenfeng; Shen, Jacson; Yang, Xiaoqian; Yang, Pei; Osaka, Eiji; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry; Hornicek, Francis] Massachusetts Gen Hosp, Dept Orthoped Surg, Sarcoma Biol Lab, Boston, MA 02114 USA. [Zhang, Yu] Liu Hua Qiao Hosp, Dept Orthoped Surg, Guangzhou 510010, Guangdong, Peoples R China. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Spentzos, Dimitrios] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Sarcoma Program,Div Hematol Oncol, Boston, MA 02215 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Sarcoma Biol Lab, Boston, MA 02114 USA. EM zduan@partners.org OI Cote, Gregory/0000-0003-0181-886X FU Stephan L. Harris Fund; Gattegno and Wechsler Funds; Chordoma Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA151452-01]; Academic Enrichment Fund of MGH Orthopedic Surgery FX Grant sponsor: Stephan L. Harris Fund; Grant sponsor: Gattegno and Wechsler Funds; Grant sponsor: Chordoma Foundation; Grant sponsor: Sarcoma Foundation of America (SFA); Grant sponsor: National Cancer Institute (NCI)/National Institutes of Health (NIH); Grant numbers: UO1, CA151452-01; Grant sponsor: Academic Enrichment Fund of MGH Orthopedic Surgery. NR 33 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2014 VL 32 IS 5 BP 695 EP 701 DI 10.1002/jor.22589 PG 7 WC Orthopedics SC Orthopedics GA AC9GL UT WOS:000332842300011 PM 24501096 ER PT J AU Kelley, AS Langa, KM Smith, AK Cagle, J Ornstein, K Silveira, MJ Nicholas, L Covinsky, KE Ritchie, CS AF Kelley, Amy S. Langa, Kenneth M. Smith, Alexander K. Cagle, John Ornstein, Katherine Silveira, Maria J. Nicholas, Lauren Covinsky, Kenneth E. Ritchie, Christine S. TI Leveraging the Health and Retirement Study To Advance Palliative Care Research SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID LAST 6 MONTHS; RESEARCH PRIORITIES; UNITED-STATES; SERIOUS ILLNESS; OLDER-ADULTS; LATER LIFE; NURSING-HOMES; DEMOGRAPHICS; DEMENTIA; MEMORY AB Background: The critical need to expand and develop the palliative care evidence base was recently highlighted by the Journal of Palliative Medicine's series of articles describing the Research Priorities in Geriatric Palliative Care. The Health and Retirement Study (HRS) is uniquely positioned to address many priority areas of palliative care research. This nationally representative, ongoing, longitudinal study collects detailed survey data every 2 years, including demographics, health and functional characteristics, information on family and caregivers, and personal finances, and also conducts a proxy interview after each subject's death. The HRS can also be linked with Medicare claims data and many other data sources, e.g., U.S. Census, Dartmouth Atlas of Health Care. Setting: While the HRS offers innumerable research opportunities, these data are complex and limitations do exist. Therefore, we assembled an interdisciplinary group of investigators using the HRS for palliative care research to identify the key palliative care research gaps that may be amenable to study within the HRS and the strengths and weaknesses of the HRS for each of these topic areas. Conclusion: In this article we present the work of this group as a potential roadmap for investigators contemplating the use of HRS data for palliative care research. C1 [Kelley, Amy S.; Ornstein, Katherine] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kelley, Amy S.] James J Peters VA Med Ctr, Geriatr Res Educ Ctr, Bronx, NY USA. [Kelley, Amy S.] James J Peters VA Med Ctr, Clin Ctr, Bronx, NY USA. [Langa, Kenneth M.; Silveira, Maria J.] Vet Adm Ann Arbor, Ctr Clin Mangement Res, Ann Arbor, MI USA. [Langa, Kenneth M.; Silveira, Maria J.] Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. [Langa, Kenneth M.; Nicholas, Lauren] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Langa, Kenneth M.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [Langa, Kenneth M.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Smith, Alexander K.; Covinsky, Kenneth E.; Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Cagle, John] Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA. RP Kelley, AS (reprint author), Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM amy.kelley@mssm.edu FU National Palliative Care Research Center; Advanced Illness and Multimorbidity Geriatric Academic Leadership Award [1K07AG31779]; Improving Care for Older Adults with Serious Illness National Institute on Aging [1K23AG040774-01A1]; American Federation for Aging Research; National Institute on Aging [U01 AG009740]; Social Security Administration FX Funded by the National Palliative Care Research Center; Advanced Illness and Multimorbidity Geriatric Academic Leadership Award (1K07AG31779); Improving Care for Older Adults with Serious Illness National Institute on Aging (1K23AG040774-01A1); and the American Federation for Aging Research.; The Health and Retirement Study is funded by the National Institute on Aging (U01 AG009740) and the Social Security Administration, and is performed at the Institute for Social Research, University of Michigan. NR 40 TC 2 Z9 2 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY 1 PY 2014 VL 17 IS 5 BP 506 EP 511 DI 10.1089/jpm.2013.0648 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AG7EV UT WOS:000335581800005 PM 24694096 ER PT J AU Berkowitz, RS Horowitz, NS Goldstein, DP AF Berkowitz, Ross S. Horowitz, Neil S. Goldstein, Donald P. TI Gestational Trophoblastic Disease Presentations from the XVIIth World Congress on Gestational Trophoblastic Diseases SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE gestational trophoblastic disease; gestational trophoblastic neoplasms; international collaboration; International Society for the Study of Trophoblastic Disease C1 [Goldstein, Donald P.] Harvard Univ, Brigham & Womens Hosp,Dana Farber Canc Inst, New England Trophoblast Dis Ctr,Dept Obstet & Gyn, Trophoblast Tumor Registry,Div Gynecol Oncol,Med, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2014 VL 59 IS 5-6 BP 187 EP 187 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH8WS UT WOS:000336419500002 PM 24937954 ER PT J AU Vargas, R Barroilhet, LM Esselen, K Diver, E Bernstein, M Goldstein, DP Berkowitz, RS AF Vargas, Roberto Barroilhet, Lisa M. Esselen, Katharine Diver, Elisabeth Bernstein, Marilyn Goldstein, Donald P. Berkowitz, Ross S. TI Subsequent Pregnancy Outcomes After Complete and Partial Molar Pregnancy, Recurrent Molar Pregnancy, and Gestational Trophoblastic Neoplasia An Update from the New England Trophoblastic Disease Center SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE gestational trophoblastic disease; gestational trophoblastic neoplasia; hydatidiform mole; NLRP7 protein human; pregnancy outcome ID QUALITY-OF-LIFE; HYDATIDIFORM MOLE; REPRODUCTIVE WASTAGE; NLRP7 MUTATIONS; PRETERM BIRTH; CHEMOTHERAPY; TUMORS; WOMEN; MISCARRIAGE; RISK AB OBJECTIVE: To review and update the subsequent reproductive outcomes in patients with complete, partial, and recurrent hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) at the New England Trophoblastic Disease Center. STUDY DESIGN: Patients with complete and partial hydatidiform mole, recurrent hydatidiform mole, and GTN were identified from the Donald P. Goldstein, M.D., Trophoblastic Tumor Registry. Questionnaires regarding subsequent pregnancies were mailed to patients with current mailing addresses available. Additional patient data was obtained from electronic medical records. RESULTS: A total of 2,432 subsequent pregnancies have been reported since 1965. Of those, 1,388 pregnancies were after complete mole, 357 after partial mole, and 667 after GTN. The subsequent reproductive outcomes in patients with complete and partial molar pregnancies and persistent GTN remain similar to those in the general population. However, approximately 1.7% of patients with a prior molar pregnancy had a molar pregnancy in a later gestation. Furthermore, after successful chemotherapy for GTN the incidence of stillbirth was slightly increased to 1.3% in later pregnancies. CONCLUSION: Patients with molar pregnancies and GTN should expect similar reproductive outcomes as compared to the general population. However, patients receiving chemotherapy for GTN have a slightly increased risk of stillbirth in subsequent pregnancies. C1 Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol,Dana Farber Canc Inst,Med S, Boston, MA 02115 USA. [Goldstein, Donald P.] New England Trophoblast Dis Ctr, Trophoblast Tumor Registry, Boston, MA USA. Univ Wisconsin Hosp & Clin, Div Gynecol Oncol, Madison, WI 53792 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 45 TC 11 Z9 13 U1 1 U2 7 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2014 VL 59 IS 5-6 BP 188 EP 194 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH8WS UT WOS:000336419500003 PM 24937955 ER PT J AU Fulop, V Szigetvari, I Szepesi, J Vegh, G Berkowitz, RS AF Fueloep, Vihnos Szigetvari, Ivan Szepesi, Janos Vegh, Gyoergy Berkowitz, Ross S. TI Changes in the Management of High-risk Gestational Trophoblastic Neoplasia in the National Trophoblastic Disease Center of Hungary SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE anatomical stages; chemotherapy; gestational trophoblastic disease; gestational trophoblastic neoplasia; prognostic score ID FACTOR SCORING SYSTEM; ACTINOMYCIN-D; CHEMOTHERAPY; METHOTREXATE; ETOPOSIDE; REGIMEN; TUMORS AB OBJECTIVE: To compare the clinical management of patients with high-risk gestational trophoblastic neoplasia (GTN) among the periods of 1977-1990, 1991-2000, and 2001-2012 at the National Trophoblastic Disease Center of Hungary and to assess the efficacy of the FIGO 2000 staging and risk factor scoring system in comparison to the original WHO prognostic scoring system (1983). STUDY DESIGN: We reviewed the medical records of 185 patients with high-risk GTN. From 1977-2000, patients were classified according to the original WHO prognostic scoring system (1983). From 2001-2012, high-risk patients were categorized by the FIGO 2000 system. We assessed the efficacy of MAC and EMA-CO primary combination chemotherapies. For 1977-2006 and 2007-2012 we assessed the efficacy of MAC and EMA-CO primary combination chemotherapies. RESULTS: From 1977-1990, 63 high-risk patients (average, 4-5 patients/year), from 1991-2000, 50 high-risk patients (average, 5 patients/year), and from 2001-2012, 72 high-risk patients (average, 6 patients/year) were treated primarily with combination chemotherapy (MAC and/or EMA-CO and/or CEB). From 1977-2006, 100 high-risk patients received MAC primary combination chemotherapy and 17 cases received EMA-CO. The ratio of primary MAC and EMA-CO therapy among our high-risk patients was 5.9 (100/17) over the referred period. From 2007 2012, 21 high-risk patients were treated with primary MAC chemotherapy and 16 patients received EMA-CO. The MAC/EMA-CO ratio over this time interval was 1.3 (21/16)., CONCLUSION: We attained complete remission in 95.7% of the high-risk patients. During the last 6 years the use of EMA-CO primary combination chemotherapy increased among our high-risk patients, which has resulted in increased efficacy and fewer side effects. C1 [Fueloep, Vihnos] State Hlth Ctr, Dept Obstet & Gynecol, H-1062 Budapest, Hungary. Peterfy Hosp, Budapest, Hungary. Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol,Med Sch, New England Trophoblast Dis Ctr,Dana Farber Canc, Boston, MA 02115 USA. RP Fulop, V (reprint author), State Hlth Ctr, Dept Obstet & Gynecol, 111 Podmaniczky St, H-1062 Budapest, Hungary. EM fulopvilmos@freemail.hu NR 15 TC 0 Z9 0 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2014 VL 59 IS 5-6 BP 227 EP 234 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH8WS UT WOS:000336419500010 PM 24937962 ER PT J AU Mehta, DD Rudoy, D Wolfe, PJ AF Mehta, Daryush D. Rudoy, Daniel Wolfe, Patrick J. TI Kalman-based autoregressive moving average modeling and inference for formant and antiformant tracking (vol 132, pg 1732, 2012) SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Correction C1 [Mehta, Daryush D.; Rudoy, Daniel] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Wolfe, Patrick J.] UCL, Dept Stat Sci, London WC1E 6BT, England. [Wolfe, Patrick J.] UCL, Dept Comp Sci, London WC1E 6BT, England. RP Mehta, DD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. EM daryush.mehta@alum.mit.edu NR 2 TC 0 Z9 0 U1 0 U2 2 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 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2014 VL 135 IS 5 BP 3128 EP 3128 DI 10.1121/1.4869982 PG 1 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AH5HV UT WOS:000336160000067 ER PT J AU Boland, GW Duszak, R Kalra, M AF Boland, Giles W. Duszak, Richard, Jr. Kalra, Mannudeep TI Protocol Design and Optimization SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID CT; RADIATION C1 [Boland, Giles W.; Kalra, Mannudeep] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Boland, GW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 7 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2014 VL 11 IS 5 BP 440 EP 441 DI 10.1016/j.jacr.2014.01.021 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH5TE UT WOS:000336193200004 PM 24793037 ER PT J AU Lackey, AE Moshiri, M Pandey, T Lall, C Lalwani, N Bhargava, P AF Lackey, Amanda E. Moshiri, Mariam Pandey, Tarun Lall, Chandana Lalwani, Neeraj Bhargava, Puneet TI Productivity, Part 1: Getting Things Done, Using E-Mail, Scanners, Reference Managers, Note-taking Applications, and Text Expanders SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Productivity; workflow; time management AB In an era of declining reimbursements and tightening of the job market, today's radiologists are forced to "make do with less." With the rollout of the Patient Protection and Affordable Care Act, commonly called "Obamacare," radiologists will be expected not only to interpret studies but to also take on many additional roles, adding a new layer of complexity to already demanding daily duties. These changes make it more important than ever to develop a personal workflow management system incorporating some of the most potent productivity tools. In this article, the authors discuss current productivity techniques and related software with the most potential to help radiologists keep up with the ever increasing demands on their time at the work place and help us lead more balanced lives. C1 [Lackey, Amanda E.; Pandey, Tarun] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. [Moshiri, Mariam; Lalwani, Neeraj] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Lall, Chandana] Univ Calif Irvine, Orange, CA 92668 USA. [Bhargava, Puneet] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Bhargava, P (reprint author), Univ Washington, Mail Box 358280,S-114 Radiol, Seattle, WA 98108 USA. EM bhargp@uw.edu RI Lalwani, Neeraj/A-3490-2011; OI Lalwani, Neeraj/0000-0001-5514-2805; Bhargava, Puneet/0000-0002-3849-9666 NR 24 TC 3 Z9 3 U1 3 U2 14 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 MAY PY 2014 VL 11 IS 5 BP 481 EP 489 DI 10.1016/j.jacr.2013.11.020 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH5TE UT WOS:000336193200012 PM 24656443 ER PT J AU Prabhakar, AM Oklu, R Harvey, HB Harisinghani, MG Rosman, DA AF Prabhakar, Anand M. Oklu, Rahmi Harvey, H. Benjamin Harisinghani, Mukesh G. Rosman, David A. TI The Radiology Job Market: Analysis of the ACR Jobs Board SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiologist; employment; job market AB Purpose: The aim of this study was to assess the status of the radiology job market as represented by the ACR Jobs Board from October 2010 to June 2013. Methods: With the assistance of the ACR, data from the ACR Jobs Board from October 2010 through June 2013, including the numbers of monthly new job seekers, new job postings, and job posting clicks, were gathered and used to calculate a monthly competitive index, defined as the ratio of new job seekers to new job postings. Results: During the study period, the mean number of new job seekers was 168 per month, which was significantly greater than the 84 average new job postings for any given month (P = .0002). There was no significant difference between 2011 and 2012 with regard to the number of new job seekers or job postings. Over the time period assessed, more new job seekers registered in October and November 2010, August to November 2011, and October and November 2012. These periods were also associated with the highest competitive index values. There were less job seekers in the winter and spring of 2011, 2012, and 2013, periods associated with lower competitive index values. ACR Jobs Board activity, measured by job posting clicks, was significantly higher in 2012 than in 2011 (P < .004). Conclusions: On the basis of the ACR Jobs Board, there were consistently more new job seekers than job postings throughout the study period, and fall is the period in the year most associated with the highest competitive index for radiologist employment. C1 [Prabhakar, Anand M.; Harisinghani, Mukesh G.; Rosman, David A.] Harvard Univ, Massachusetts Gen Hosp, Div Abdominal Imaging, Med Sch,Dept Radiol, Boston, MA 02114 USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Med Sch,Dept Radiol, Boston, MA 02114 USA. [Harvey, H. Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Abdominal Imaging, Med Sch,Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM aprabhakar@partners.org NR 7 TC 3 Z9 3 U1 1 U2 1 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 MAY PY 2014 VL 11 IS 5 BP 507 EP 511 DI 10.1016/j.jacr.2013.10.001 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH5TE UT WOS:000336193200016 PM 24429184 ER PT J AU Sabir, SH Aran, S Abujudeh, H AF Sabir, Sharjeel H. Aran, Shima Abujudeh, Hani TI Simulation-Based Training in Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiology; simulation; training; quality; principle of nonmaleficence; apprenticeship model ID ON-CALL RESPONSIBILITIES; HIGH-FIDELITY SIMULATION; MEDICAL-EDUCATION; HEALTH-CARE; WORK HOURS; RESIDENTS; READINESS; COMPETENCE; MANAGEMENT; HISTORY AB Although the apprenticeship model of medical training has been in use for centuries, there are several problems with its use. The fundamental ethical principle of nonmaleficence requires that no preventable harm come to patients involved in the training process. In addition, changing medical practice patterns with shorter hospital stays and duty-hour restrictions are making it difficult for trainees to be exposed to enough patients to prepare them to deal with the many possible scenarios they may face in practice. Despite these limitations, the apprenticeship model cannot be completely rejected because it is essential for trainees to perfect their technique by caring for real patients with the guidance of experienced practitioners. Simulation-based training can allow novices to learn from their mistakes in a safe environment and in accordance with the principles of deliberate practice, thus allowing simulation to be a bridge to help get trainees from the novice state, in which they have a higher risk of causing harm, to a more experienced state in which they are more likely to do what is needed for patients. C1 [Sabir, Sharjeel H.; Aran, Shima; Abujudeh, Hani] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Abujudeh, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM habujudeh@partners.org NR 40 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAY PY 2014 VL 11 IS 5 BP 512 EP 517 DI 10.1016/j.jacr.2013.02.008 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH5TE UT WOS:000336193200017 PM 23770063 ER PT J AU Hakroush, S Cebulla, A Schaldecker, T Behr, D Mundel, P Weins, A AF Hakroush, Samy Cebulla, Angelika Schaldecker, Thomas Behr, Daniel Mundel, Peter Weins, Astrid TI Extensive Podocyte Loss Triggers a Rapid Parietal Epithelial Cell Response SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; ADRIAMYCIN NEPHROPATHY; ANIMAL-MODELS; INJURY; PROTEIN; HIV; DNA; PATHOGENESIS; RECRUITMENT; PAMIDRONATE AB Damage to podocytes is a central pathomechanism of proteinuric kidney disease. However, it is not fully understood how podocyte injury evolves to progressive glomerulopathies such as FSGS or collapsing glomerulopathy. In particular, the role of parietal epithelial cells remains controversial. Here, we show that adriamycin induces DNA damage and podocyte lysis in mice without evidence of autophagy, endoplasmic reticulum stress, or necroptosis. After extensive podocyte loss, activated parietal cells mediated tuft re-epithelialization by two distinct mechanisms. In the majority of glomeruli, vacuolized parietal epithelial cells attached to denuded glomerular basement membrane and, occasionally, disengaged from the parietal basement membrane. Less frequently, parietal epithelial cells covered the denuded visceral basement membrane via formation of proliferative pseudocrescents. Notably, visceralized parietal epithelial cells did not express vascular endothelial growth factor but upregulated hypoxia-inducible factor 1 expression. The presence of visceralized parietal epithelial cells in sclerosing and collapsing lesions in a kidney biopsy from a patient with diabetes underscores the human relevance of our findings. In conclusion, repopulation of the glomerular tuft by parietal cells may represent a compensatory response to extensive podocyte loss. Our results suggest, however, that visceralized parietal epithelial cells cannot induce revascularization of the hyalinized tuft, resulting in hypoxic cell death and irreversible destruction of the glomerulus. C1 [Hakroush, Samy; Cebulla, Angelika; Schaldecker, Thomas; Behr, Daniel; Mundel, Peter; Weins, Astrid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA. [Weins, Astrid] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weins, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Amory 3,75 Francis St, Boston, MA 02115 USA. EM aweins@partners.org FU Deutsche Forschungsgemeinschaft [HA 6334/1-1]; Boehringer Ingelheim Fonds; NIH National Institute of Diabetes and Digestive and Kidney Diseases [DK57683, DK062472, DK091218, DK093378] FX S.H. is supported by a research stipend from the Deutsche Forschungsgemeinschaft (HA 6334/1-1). A.C., T.S., and D.B. are supported by student fellowship stipends from Boehringer Ingelheim Fonds. P.M. and A.W. are supported by grants from the NIH National Institute of Diabetes and Digestive and Kidney Diseases (DK57683, DK062472, and DK091218 to P.M. and DK093378 to A.W.). NR 35 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2014 VL 25 IS 5 BP 927 EP 938 DI 10.1681/ASN.2013070687 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA AG7FM UT WOS:000335583700013 PM 24335975 ER PT J AU Coca, SG Garg, AX Thiessen-Philbrook, H Koyner, JL Patel, UD Krumholz, HM Shlipak, MG Parikh, CR AF Coca, Steven G. Garg, Amit X. Thiessen-Philbrook, Heather Koyner, Jay L. Patel, Uptal D. Krumholz, Harlan M. Shlipak, Michael G. Parikh, Chirag R. CA TRIBE-AKI Consortium TI Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; PERITUBULAR CAPILLARIES; POOR OUTCOMES; DISEASE; RECLASSIFICATION; ASSOCIATION; PROTEINURIA; DAMAGE; RISK AB The endothelin system has emerged as a novel target for the treatment of diabetic nephropathy. Endothelin-1 promotes mesangial cell proliferation and sclerosis. However, no direct pathogenic effect of endothelin-1 on podocytes has been shown in vivo and endothelin-1 signaling in podocytes has not been investigated. This study investigated endothelin effects in podocytes during experimental diabetic nephropathy. Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs). We then generated mice with a podocyte-specific double deletion of ETAR and ETBR (NPHS2-CrexEdnra(lox/lox)xEdnrb(lox/lox) [Pod-ETRKO]). In vitro, treatment with endothelin-1 increased total beta-catenin and phospho-NF-kappa B expression in wild-type glomeruli, but this effect was attenuated in Pod-ETRKO glomeruli. After streptozotocin injection to induce diabetes, wild-type mice developed mild diabetic nephropathy with microalbuminuria, mesangial matrix expansion, glomerular basement membrane thickening, and podocyte loss, whereas Pod-ETRKO mice presented less albuminuria and were completely protected from glomerulosclerosis and podocyte loss, even when uninephrectomized. Moreover, glomeruli from normal and diabetic Pod-ETRKO mice expressed substantially less total beta-catenin and phospho-NF-kappa B compared with glomeruli from counterpart wild-type mice. This evidence suggests that endothelin-1 drives development of glomerulosclerosis and podocyte loss through direct activation of endothelin receptors and NF-kappa B and beta-catenin pathways in podocytes. Notably, both the expression and function of the ETBR subtype were found to be important. Furthermore, these results indicate that activation of the endothelin-1 pathways selectively in podocytes mediates pathophysiologic crosstalk that influences mesangial architecture and sclerosis. C1 [Coca, Steven G.; Parikh, Chirag R.] Yale Univ, Sch Med, Program Appl Translat Res, Sch Med,Vet Affairs Connecticut Healthcare Syst, New Haven, CT 06510 USA. [Garg, Amit X.; Thiessen-Philbrook, Heather] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Koyner, Jay L.] Univ Chicago, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Krumholz, Harlan M.] Yale Univ, Ctr Outcomes Res & Evaluat, Yale New Haven Hosp, Sect Cardiovasc Med,Dept Internal Med,Sch Med, New Haven, CT 06510 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Parikh, CR (reprint author), Yale Univ, Sch Med, Nephrol Sect, 60 Temple Street,Suite 6C, New Haven, CT 06510 USA. EM chirag.parikh@yale.edu FU National Institutes of Health (NIH) [R01HL085757]; NIH [K23DK080132, K24DK090203, U01DK082185]; Ontario Ministry of Health and Long-Term Care FX The urine biomarker assays were donated by Abbott Diagnostics (IL-18 and NGAL) and Sekisui Diagnostics LLC (KIM-1 and L-FABP). This study was supported by the National Institutes of Health (NIH) (R01HL085757 to C.R.P.) to fund the TRIBE-AKI Consortium to study novel biomarkers of AKI in cardiac surgery. S.G.C. has been supported by an NIH Career Development Award (K23DK080132). C.R.P. is supported by the NIH (K24DK090203). S.G.C., A.X.G., and C.R.P. are also members of the NIH-sponsored Assess, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Consortium (U01DK082185). The granting agencies, Abbott Diagnostics, and Sekisui Diagnostics, Inc. did not participate in the design and conduct of the study, collection, management, analysis, and interpretation of the data, and preparation, review, or approval of the manuscript. The Institute for Clinical Evaluative Sciences receives funding from the Ontario Ministry of Health and Long-Term Care. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. The results presented in this article have not been published previously in whole or part, except in abstract form. NR 27 TC 31 Z9 31 U1 1 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2014 VL 25 IS 5 BP 1063 EP 1071 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AG7FM UT WOS:000335583700024 PM 24357673 ER PT J AU Corbelli, J Borrero, S Bonnema, R McNamara, M Kraemer, K Rubio, D Karpov, I McNeil, M AF Corbelli, Jennifer Borrero, Sonya Bonnema, Rachel McNamara, Megan Kraemer, Kevin Rubio, Doris Karpov, Irina McNeil, Melissa TI Differences Among Primary Care Physicians' Adherence to 2009 ACOG Guidelines for Cervical Cancer Screening SO JOURNAL OF WOMENS HEALTH LA English DT Article ID BREAST-CANCER; HUMAN-PAPILLOMAVIRUS; WOMENS HEALTH; HEART-FAILURE; UNITED-STATES; ATTITUDES; RECOMMENDATIONS; PREFERENCES; MANAGEMENT; INTERVALS AB Background: In 2009, the American Congress of Obstetrics and Gynecology (ACOG) guidelines for cervical cancer screening changed significantly, to recommend less frequent screening than prior guidelines. The extent to which physicians in different specialties implemented these guidelines in the years following publication is unknown. Methods: Cross-sectional survey completed by 316 physicians in internal medicine, family medicine, and gynecology. Survey items assessed respondents' cervical cancer screening practices in women of different ages and medical histories. We used descriptive statistics to generate response distribution for survey items, and logistic regression models to compare responses among specialties. Results: Our response rate was 55% (316/575). Thirty-four percent of respondents' screening practices were inconsistent with ACOG guidelines for women under age 21, and 49% were inconsistent with guidelines for women over age 30. Internists (50%) were less likely than family medicine (89%, p<0.001) and gynecology (80%, p=0.02) physicians to delay pap testing until age 21. Internists (41%) were less likely than both family medicine (60%, p=0.009) and gynecology (68%, p=0.03) physicians to follow guidelines for women over age 30 (p=0.003). Overall 22% percent of physicians followed guidelines for women ages 21-29 years, with no significant differences between specialties. Differences remained significant in multivariable models. Conclusions: Despite consensus among national organizations as to optimal regimens for cervical cancer screening, a significant proportion of providers, especially in internal medicine, do not adhere to ACOG's 2009 guidelines. The lack of comprehensive guideline implementation suggests that adherence to new 2012 guidelines, which advocate for less frequent screening, will likely be suboptimal and discrepant by specialty. C1 [Corbelli, Jennifer; Borrero, Sonya; Kraemer, Kevin; Rubio, Doris; McNeil, Melissa] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Res Hlth Equity & Promot, Pittsburgh, PA USA. [Borrero, Sonya; Kraemer, Kevin; Rubio, Doris; Karpov, Irina] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Bonnema, Rachel] Univ Nebraska Med Ctr, Div Gen Internal Med, Omaha, NE USA. [McNamara, Megan] Case Western Reserve Univ, Sch Med, Div Gen Internal Med, Cleveland, OH USA. [McNamara, Megan] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. RP Corbelli, J (reprint author), Univ Pittsburgh, Dept Gen Internal Med, Med Ctr, 200 Lothrop St,MUH 9W-33, Pittsburgh, PA 15213 USA. EM corbellija@upmc.edu FU Thomas H. Nimick Jr. Competitive Research Fund; Department of Medicine at University of Pittsburgh; U.S. Department of Veteran's Affairs FX The Thomas H. Nimick Jr. Competitive Research Fund provided money for the purchase of iPads that were given as incentives to two randomly selected study participants. The Department of Medicine at University of Pittsburgh provided funding for data management. Dr. Corbelli's fellowship training is funded by the U.S. Department of Veteran's Affairs. These funding sources had no role in the study design or implementation, analysis of results, or manuscript preparation. NR 33 TC 11 Z9 11 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD MAY 1 PY 2014 VL 23 IS 5 BP 397 EP 403 DI 10.1089/jwh.2013.4475 PG 7 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 AG9KY UT WOS:000335739300006 PM 24380500 ER PT J AU Danielson, CK Walsh, K McCauley, J Ruggiero, KJ Brown, JL Sales, JM Rose, E Wingood, GM DiClemente, RJ AF Danielson, Carla Kmett Walsh, Kate McCauley, Jenna Ruggiero, Kenneth J. Brown, Jennifer L. Sales, Jessica M. Rose, Eve Wingood, Gina M. DiClemente, Ralph J. TI HIV-Related Sexual Risk Behavior Among African American Adolescent Girls SO JOURNAL OF WOMENS HEALTH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE; PREVENTION INTERVENTIONS; ABUSE; STRESS; IMPACT; WOMEN; DISPARITIES; PREDICTORS; PARTNERS AB Background: Latent class analysis (LCA) is a useful statistical tool that can be used to enhance understanding of how various patterns of combined sexual behavior risk factors may confer differential levels of HIV infection risk and to identify subtypes among African American adolescent girls. Methods: Data for this analysis is derived from baseline assessments completed prior to randomization in an HIV prevention trial. Participants were African American girls (n=701) aged 14-20 years presenting to sexual health clinics. Girls completed an audio computer-assisted self-interview, which assessed a range of variables regarding sexual history and current and past sexual behavior. Results: Two latent classes were identified with the probability statistics for the two groups in this model being 0.89 and 0.88, respectively. In the final multivariate model, class 1 (the higher risk group; n=331) was distinguished by a higher likelihood of >5 lifetime sexual partners, having sex while high on alcohol/drugs, less frequent condom use, and history of sexually transmitted diseases (STDs), when compared with class 2 (the lower risk group; n=370). The derived model correctly classified 85.3% of participants into the two groups and accounted for 71% of the variance in the latent HIV-related sexual behavior risk variable. The higher risk class also had worse scores on all hypothesized correlates (e.g., self-esteem, history of sexual assault or physical abuse) relative to the lower risk class. Conclusions: Sexual health clinics represent a unique point of access for HIV-related sexual risk behavior intervention delivery by capitalizing on contact with adolescent girls when they present for services. Four empirically supported risk factors differentiated higher versus lower HIV risk. Replication of these findings is warranted and may offer an empirical basis for parsimonious screening recommendations for girls presenting for sexual healthcare services. C1 [Danielson, Carla Kmett; McCauley, Jenna; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Walsh, Kate] Columbia Univ, Dept Epidemiol, New York, NY USA. [Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Brown, Jennifer L.; Sales, Jessica M.; Rose, Eve; Wingood, Gina M.; DiClemente, Ralph J.] Texas Tech Univ, Dept Psychol, Lubbock, TX 79409 USA. [Sales, Jessica M.; Wingood, Gina M.; DiClemente, Ralph J.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Sales, Jessica M.; Wingood, Gina M.; DiClemente, Ralph J.] Emory Univ, Rollins Sch Publ Hlth, Ctr AIDS Res, Atlanta, GA 30322 USA. [Sales, Jessica M.; Wingood, Gina M.; DiClemente, Ralph J.] Emory Univ, Sch Med, Dept Pediat, Div Infect Dis Epidemiol & Immunol, Atlanta, GA USA. RP Danielson, CK (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, MSC 861,Suite 207, Charleston, SC 29425 USA. EM danielso@musc.edu FU National Institute of Mental Health (NIMH) [5R01MH070537]; National Institute on Drug Abuse (NIDA) [K23DA018686, R01DA031285]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [P50 AA010761] FX The study was supported by grant award 5R01MH070537 from the National Institute of Mental Health (NIMH; PI: DiClemente). The preparation of this manuscript was supported by grant awards K23DA018686 and R01DA031285 from the National Institute on Drug Abuse (NIDA; PI: Danielson) and grant award P50 AA010761 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA; Center PI: Becker). The views, policies, and opinions expressed in this article are those of the authors and do not necessarily reflect those of NIMH, NIDA, and NIAAA. NR 40 TC 3 Z9 3 U1 3 U2 14 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD MAY 1 PY 2014 VL 23 IS 5 BP 413 EP 419 DI 10.1089/jwh.2013.4599 PG 7 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 AG9KY UT WOS:000335739300008 PM 24749895 ER PT J AU Kinsey, CM Estepar, RSJ Zhao, Y Yu, X Diao, N Heist, RS Wain, JC Mark, EJ Washko, G Christiani, DC AF Kinsey, C. Matthew Estepar, Raul San Jose Zhao, Yang Yu, Xiaojin Diao, Nancy Heist, Rebecca Suk Wain, John C. Mark, Eugene J. Washko, George Christiani, David C. TI Invasive adenocarcinoma of the lung is associated with the upper lung regions SO LUNG CANCER LA English DT Article DE Non-small cell lung cancer; Tumor location; Emphysema ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; COMPUTED-TOMOGRAPHY; CANCER-RISK; EMPHYSEMA; VOLUME; CT; METAANALYSIS; LOCATION; SCAN AB Objectives: We postulated that ventilation perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior inferior regional distribution, and associated variables such as emphysema. Materials and Methods: One hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema. Results: The majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P=0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P=0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P=0.008, compared to lower region), whereas lobar location of tumor was not (P=0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (P=0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P=0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P=0.217). Conclusion: Invasive adenocarcinoma of the lung is highly associated with the upper lung regions. This association is not related to smoking, history of COPD, or total emphysema. The regional distribution of invasive adenocarcinoma may be due to V/Q relationships or other local factors. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Kinsey, C. Matthew] Univ Vermont, Div Pulm & Crit Care, Coll Med, Burlington, VT 05405 USA. [Estepar, Raul San Jose; Diao, Nancy; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth & Epidemiol, Boston, MA 02115 USA. [Estepar, Raul San Jose] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Zhao, Yang] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Yu, Xiaojin] Southeast Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Heist, Rebecca Suk] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Wain, John C.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Washko, George] Brigham & Womens Hosp, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth & Epidemiol, Bldg 1,Room 1401,665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU [CA092824]; [CA074386]; [CA090578] FX Research Support: Supported by Grants No. CA092824 (D.C.C.), CA074386 (D.C.C.), and CA090578 (D.C.C.) NR 25 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD MAY PY 2014 VL 84 IS 2 BP 145 EP 150 DI 10.1016/j.lungcan.2014.02.002 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AH7WN UT WOS:000336346200010 PM 24598367 ER PT J AU Golob, AL Wipf, JE AF Golob, Anna L. Wipf, Joyce E. TI Low Back Pain SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Acute low back pain; Chronic low back pain; Risk factors; Cause; Diagnosis; Imaging; Treatment; Sciatica ID CLINICAL-PRACTICE GUIDELINE; RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; LUMBAR SPINE; AMERICAN-COLLEGE; INCEPTION COHORT; PREVALENCE; SOCIETY; EPIDEMIOLOGY; DISABILITY AB Low back pain is one of the most frequent complaints for which patients are seen in primary care. Low back pain has a substantial economic impact, estimated at $100 billion per year including direct and indirect costs. The evaluation of low back pain involves a thorough history and physical examination. Imaging is only indicated when a more serious underlying cause or neurologic abnormality is suspected. Abnormalities detected on imaging do not strongly correlate with symptoms. Generally, a specific underlying cause for low back pain is not identified. Treatment consists of a multidisciplinary approach with goal to maintain function and minimize disability. C1 [Golob, Anna L.; Wipf, Joyce E.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Golob, Anna L.; Wipf, Joyce E.] VA Puget Sound Healthcare Syst, Gen Med Serv, Seattle, WA 98108 USA. RP Golob, AL (reprint author), VA Puget Sound Healthcare Syst, Gen Med Serv, S-123 PCC,1660 South Columbian Way, Seattle, WA 98108 USA. EM zilanna@uw.edu FU UpToDate chapter royalties FX Financial Disclosures: None (A.L. Golob); UpToDate chapter royalties (J.E. Wipf). NR 48 TC 6 Z9 10 U1 1 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2014 VL 98 IS 3 BP 405 EP + DI 10.1016/j.mcna.2014.01.003 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA AH5RK UT WOS:000336188500003 PM 24758954 ER PT J AU Berger, D AF Berger, Douglas TI Leg Discomfort: Beyond the Joints SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Leg pain; Paresthesia; Claudication; Neuropathy; Myalgia; Cramp ID LUMBAR SPINAL STENOSIS; PERIPHERAL ARTERIAL-DISEASE; CLINICAL-PRACTICE GUIDELINES; DEEP-VEIN THROMBOSIS; MERALGIA-PARESTHETICA; LOWER-EXTREMITY; MUSCLE CRAMPS; MUSCULOSKELETAL PAIN; DIAGNOSTIC-CRITERIA; AMERICAN-COLLEGE AB Although discussions of leg pain usually begin with the hip, knee, and ankle, patients often present with leg symptoms unrelated to articular or periarticular structures. Pain, paresthesias, cramping, heaviness, or numbness may arise from a variety of vascular, neurologic, and musculoskeletal causes beyond the joints. This article describes the presentation, diagnosis, and treatment of common causes of such symptoms, including peripheral arterial disease, chronic venous insufficiency, deep vein thrombosis, lumbosacral radiculopathy, lumbar spinal stenosis, peripheral neuropathy, statin myalgia, cramps, and restless legs syndrome. C1 Univ Washington, VA Puget Sound, Dept Med, Gen Med Serv, Seattle, WA 98108 USA. RP Berger, D (reprint author), Univ Washington, VA Puget Sound, Dept Med, Gen Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM douglas.berger@va.gov NR 91 TC 2 Z9 2 U1 0 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2014 VL 98 IS 3 BP 429 EP + DI 10.1016/j.mcna.2014.01.004 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA AH5RK UT WOS:000336188500004 PM 24758955 ER PT J AU Overland, MK AF Overland, Maryann Katherine TI Dyspepsia SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Functional dyspepsia; Helicobacter pylori test and treat; Peptic ulcer disease; Gastroesophageal reflux disease ID PLACEBO-CONTROLLED TRIAL; GASTROESOPHAGEAL-REFLUX DISEASE; FUNCTIONAL GASTRODUODENAL DISORDERS; HELICOBACTER-PYLORI ERADICATION; RANDOMIZED CLINICAL-TRIAL; PROTON PUMP INHIBITOR; DOUBLE-BLIND; GASTRIC ACCOMMODATION; NONULCER DYSPEPSIA; SYMPTOMS AB Dyspepsia is a common and complex condition consisting of chronic upper gastrointestinal symptoms. A rational approach to diagnosis and treatment of dyspepsia includes identifying those patients with alarm symptoms and referring them for prompt endoscopy. Those without alarm symptoms can be differentiated into patients who do and do not have symptoms consistent with gastroesophageal reflux disease. In the absence of predominant heartburn and regurgitation, patients should be tested and treated for Helicobacter pylori. Functional (nonulcer) dyspepsia is a multifactorial disorder with several possible pathophysiologic mechanisms, but no clear guidelines for therapy. There is some evidence of efficacy of proton pump inhibitors, antisecretory agents, antidepressants, and psychotherapy for functional dyspepsia. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Primary Care Clin, Div Gen Internal Med, Seattle, WA 98108 USA. RP Overland, MK (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Primary Care Clin, Div Gen Internal Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Maryann.Overland@va.gov NR 68 TC 5 Z9 6 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2014 VL 98 IS 3 BP 549 EP + DI 10.1016/j.mcna.2014.01.007 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA AH5RK UT WOS:000336188500009 PM 24758960 ER PT J AU Molnar, A McGee, S AF Molnar, Alexandra McGee, Steven TI Diagnosing and Treating Dizziness SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Dizziness; Vertigo; Epley; Primary care ID PAROXYSMAL POSITIONAL VERTIGO; HEAD IMPULSE TEST; MENIERES-DISEASE; DIZZY PATIENT; PERSISTENT DIZZINESS; EMERGENCY-DEPARTMENT; ELDERLY-PATIENTS; PRIMARY-CARE; POPULATION; COMMUNITY AB Dizziness is a common presenting concern in primary care practice. The most useful diagnostic approach in distinguishing different types of dizziness is a thorough history and physical examination; additional tests are rarely necessary. Effective treatments exist for many causes of dizziness, and these treatments are often accomplished in the clinic or at home without the need for medication. C1 [Molnar, Alexandra] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [McGee, Steven] Univ Washington, Dept Med, Vet Affairs Puget Sound Healthcare Syst, Seattle Div, Seattle, WA 98108 USA. RP Molnar, A (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Box 359895,325 9th Ave, Seattle, WA 98104 USA. EM amolnar@uw.edu OI Molnar, Alexandra/0000-0003-3258-6782 NR 35 TC 3 Z9 3 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2014 VL 98 IS 3 BP 583 EP + DI 10.1016/j.mcna.2014.01.014 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA AH5RK UT WOS:000336188500011 PM 24758962 ER PT J AU Evans, G AF Evans, Ginger TI Identifying and Treating the Causes of Neck Pain SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Neck pain; Cervical spondylosis; Radiculopathy; Myelopathy; Chronic pain ID 2000-2010 TASK-FORCE; CERVICAL SPONDYLOTIC MYELOPATHY; GENERAL-POPULATION; DISK DISEASE; DIAGNOSTIC-ACCURACY; DISORDERS; RADICULOPATHY; SPINE; BONE; ROOT AB Chronic neck pain is a common and often disabling problem. It can describe pain in the neck region alone or include related disorders of radiculopathy or myelopathy. This review of the literature is aimed at the practicing primary care provider, who is diagnosing and managing non-traumatic neck pain in the clinic. It includes an anatomic review, definition of related disorders, differential diagnosis, and discussion of common diagnostic uncertainty for mechanical neck pain. Important history and physical examination techniques, the role of imaging, and the available literature on conservative and invasive treatment options are reviewed. C1 Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Evans, G (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, 1660 South Columbia Way,S-123-PCC, Seattle, WA 98108 USA. EM gingere@u.washington.edu NR 73 TC 2 Z9 2 U1 1 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2014 VL 98 IS 3 BP 645 EP + DI 10.1016/j.mcna.2014.01.015 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA AH5RK UT WOS:000336188500015 PM 24758966 ER PT J AU Stahl, JE Balasubramanian, HJ Gao, XL Overko, S Fosburgh, B AF Stahl, James E. Balasubramanian, Hari Jagannathan Gao, Xiaoling Overko, Steven Fosburgh, Blair TI Balancing Clinical Experience in Outpatient Residency Training SO MEDICAL DECISION MAKING LA English DT Article DE patient panels; access to care; continuity; resident training; education ID PRIMARY-CARE; IMPACT; MIX AB Background. To receive adequate training experience, resident panels in teaching clinics must have a sufficiently diverse patient case-mix. However, case-mix can differ from one resident panel to another, resulting in inconsistent training. Method. Encounter data from primary care residency clinics at Massachusetts General Hospital from July 2008 to May 2010 (64 residents and similar to 3800 patients) were used to characterize patients by gender, age, major disease category (both acute and chronic, e.g., Cardio Acute, Cardio Chronic, etc., for a total of 44 disease categories), and number of disease categories. Imbalance across resident panels was characterized by the standard deviation for disease category, patient panel size, and annual visit frequency. To balance case-mix in resident panels, patient reassignment algorithms were proposed. First, patients were sorted by complexity; then patients were allocated sequentially to the panel with the least overall complexity. Patient reassignment across resident panels was considered under 3 scenarios: 1) within preceptor, 2) within a group of preceptors, and 3) across the entire practice annually. Results were compared with case-mix (pre-July 2012) and post-July 2012. Results. All 3 reassignment algorithms produced significant reductions in standard deviation of either number of disease categories or diagnoses across residents when compared with baseline (pre-July 2012) and actual July 2012 reassignment. Reassignment across the clinic and group provided the best and second best scenarios, respectively, although both came at the cost of initially reduced patient-preceptor continuity. Conclusion. Systematically reallocating patient panels in teaching clinics potentially can improve the consistency and breadth of the educational experience. The method in principle can be extended to any target of health care system reform where there is patient or clinician turnover. C1 [Balasubramanian, Hari Jagannathan; Gao, Xiaoling; Overko, Steven] Univ Massachusetts, Dept Mech & Ind Engn, Amherst, MA 01003 USA. [Fosburgh, Blair] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Stahl, James E.] MGH Inst Technol Assessment, Boston, MA USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM jstahl@partners.org FU AHRQ [R03 HS 018795]; NSF [CMMI 1031550] FX Received 21 January 2013 from Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, MA (HJB, XG, SO); Division of General Medicine, Massachusetts General Hospital, Boston, MA (BWF); and MGH Institute for Technology Assessment, Boston, MA (JES). Supported by AHRQ R03 HS 018795 and NSF CMMI 1031550. Revision accepted for publication 13 January 2014. NR 15 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY PY 2014 VL 34 IS 4 BP 464 EP 472 DI 10.1177/0272989X14524304 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AF0JA UT WOS:000334398900008 PM 24639474 ER PT J AU Fritscher, KD Peroni, M Zaffino, P Spadea, MF Schubert, R Sharp, G AF Fritscher, Karl D. Peroni, Marta Zaffino, Paolo Spadea, Maria Francesca Schubert, Rainer Sharp, Gregory TI Automatic segmentation of head and neck CT images for radiotherapy treatment planning using multiple atlases, statistical appearance models, and geodesic active contours SO MEDICAL PHYSICS LA English DT Article DE radiation therapy planning; atlas-based segmentation; geodesic active contours; InShape models ID AUTO-SEGMENTATION; RISK; CONSTRUCTION; REGISTRATION; VALIDATION; SELECTION; ORGANS AB Purpose: Accurate delineation of organs at risk (OARs) is a precondition for intensity modulated radiation therapy. However, manual delineation of OARs is time consuming and prone to high inter-observer variability. Because of image artifacts and low image contrast between different structures, however, the number of available approaches for autosegmentation of structures in the head-neck area is still rather low. In this project, a new approach for automated segmentation of head-neck CT images that combine the robustness of multiatlas-based segmentation with the flexibility of geodesic active contours and the prior knowledge provided by statistical appearance models is presented. Methods: The presented approach is using an atlas-based segmentation approach in combination with label fusion in order to initialize a segmentation pipeline that is based on using statistical appearance models and geodesic active contours. An anatomically correct approximation of the segmentation result provided by atlas-based segmentation acts as a starting point for an iterative refinement of this approximation. The final segmentation result is based on using model to image registration and geodesic active contours, which are mutually influencing each other. Results: 18 CT images in combination with manually segmented labels of parotid glands and brainstem were used in a leave-one-out cross validation scheme in order to evaluate the presented approach. For this purpose, 50 different statistical appearance models have been created and used for segmentation. Dice coefficient (DC), mean absolute distance and max. Hausdorff distance between the autosegmentation results and expert segmentations were calculated. An average Dice coefficient of DC = 0.81 (right parotid gland), DC = 0.84 (left parotid gland), and DC = 0.86 (brainstem) could be achieved. Conclusions: The presented framework provides accurate segmentation results for three important structures in the head neck area. Compared to a segmentation approach based on using multiple atlases in combination with label fusion, the proposed hybrid approach provided more accurate results within a clinically acceptable amount of time. (C) 2014 American Association of Physicists in Medicine. C1 [Fritscher, Karl D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Peroni, Marta] Paul Scherrer Inst, CH-5232 Villigen, Switzerland. [Zaffino, Paolo; Spadea, Maria Francesca] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. [Schubert, Rainer] Private Univ Hlth Sci Med Informat & Technol, Inst Biomed Image Anal, A-6060 Hall In Tirol, Austria. [Sharp, Gregory] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Fritscher, KD (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM Karl.Fritscher@umit.at FU National Institutes of Health through NIH Roadmap for Medical Research [U54 EB005149] FX This work is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant No. U54 EB005149. Information on the National Centers for Biomedical Computing can be obtained from http://nihroadmap.nih.gov/bioinformatics. NR 37 TC 13 Z9 14 U1 0 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 MAY PY 2014 VL 41 IS 5 AR 051910 DI 10.1118/1.4871623 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH3VD UT WOS:000336053100026 PM 24784389 ER PT J AU Sharp, G Fritscher, KD Pekar, V Peroni, M Shusharina, N Veeraraghavan, H Yang, JZ AF Sharp, Gregory Fritscher, Karl D. Pekar, Vladimir Peroni, Marta Shusharina, Nadya Veeraraghavan, Harini Yang, Jinzhong TI Vision 20/20: Perspectives on automated image segmentation for radiotherapy SO MEDICAL PHYSICS LA English DT Article DE segmentation; radiation therapy; image processing ID ATLAS-BASED SEGMENTATION; LYMPH-NODE REGIONS; NECK CT IMAGES; INTENSITY-MODULATED RADIOTHERAPY; COMPUTED-TOMOGRAPHY IMAGES; CLINICAL TARGET VOLUME; ACTIVE SHAPE MODELS; CELL LUNG-CANCER; HEAD-AND-NECK; AUTO-SEGMENTATION AB Due to rapid advances in radiation therapy (RT), especially image guidance and treatment adaptation, a fast and accurate segmentation of medical images is a very important part of the treatment. Manual delineation of target volumes and organs at risk is still the standard routine for most clinics, even though it is time consuming and prone to intra- and interobserver variations. Automated segmentation methods seek to reduce delineation workload and unify the organ boundary definition. In this paper, the authors review the current autosegmentation methods particularly relevant for applications in RT. The authors outline the methods' strengths and limitations and propose strategies that could lead to wider acceptance of autosegmentation in routine clinical practice. The authors conclude that currently, autosegmentation technology in RT planning is an efficient tool for the clinicians to provide them with a good starting point for review and adjustment. Modern hardware platforms including GPUs allow most of the autosegmentation tasks to be done in a range of a few minutes. In the nearest future, improvements in CT-based autosegmentation tools will be achieved through standardization of imaging and contouring protocols. In the longer term, the authors expect a wider use of multi-modality approaches and better understanding of correlation of imaging with biology and pathology. (C) 2014 American Association of Physicists in Medicine. C1 [Sharp, Gregory; Fritscher, Karl D.; Shusharina, Nadya] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Pekar, Vladimir] Philips Healthcare, Markham, ON 6LC 2S3, Canada. [Peroni, Marta] Paul Scherrer Inst, Ctr Proton Therapy, CH-5232 Villigen, Switzerland. [Veeraraghavan, Harini] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10065 USA. [Yang, Jinzhong] MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Sharp, G (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM gcsharp@partners.org OI Yang, Jinzhong/0000-0002-9254-4501 FU National Alliance for Medical Image Computing (NAMIC); National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149] FX This work was funded in part by the National Alliance for Medical Image Computing (NAMIC) and funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant No. U54 EB005149. NR 105 TC 15 Z9 16 U1 2 U2 18 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 MAY PY 2014 VL 41 IS 5 AR 050902 DI 10.1118/1.4871620 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH3VD UT WOS:000336053100003 PM 24784366 ER PT J AU Brown, DN AF Brown, Douglas N. TI Ovary and unilateral oophorectomy: is having one the same as having two? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID NURSES HEALTH; CANCER; HYSTERECTOMY; EPIDEMIOLOGY; CONSERVATION; LATERALITY; OVULATION C1 Massachusetts Gen Hosp, Ctr Minimally Invas Gynecol Surg, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Brown, DN (reprint author), Massachusetts Gen Hosp, Ctr Minimally Invas Gynecol Surg, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY PY 2014 VL 21 IS 5 BP 435 EP 436 DI 10.1097/GME.0000000000000229 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH0SF UT WOS:000335829900002 PM 24667355 ER PT J AU Tanner, CM Meng, CC Ravina, B Lang, A Kurlan, R Marek, K Oakes, D Seibyl, J Flagg, E Gauger, L Guest, DD Goetz, CG Kieburtz, K DiEuliis, D Fahn, S Elliott, RA Shoulson, I AF Tanner, Caroline M. Meng, Cheryl C. Ravina, Bernard Lang, Anthony Kurlan, Roger Marek, Kenneth Oakes, David Seibyl, John Flagg, Emily Gauger, Lisa Guest, Dolores D. Goetz, Christopher G. Kieburtz, Karl DiEuliis, Diane Fahn, Stanley Elliott, Robin A. Shoulson, Ira TI A Practical Approach to Remote Longitudinal Follow-up of Parkinson's Disease: The FOUND Study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; longitudinal; follow-up ID RATING-SCALE; SYDNEY MULTICENTER; CLINICAL-TRIAL; PROGRESSION; RETENTION; DEMENTIA; RECRUITMENT; ASSESSMENTS; IMPAIRMENT; DISABILITY AB The objective of this study was to examine a remote method for maintaining long-term contact with Parkinson's disease (PD) patients participating in clinical studies. Long-term follow-up of PD patients is needed to fill critical information gaps on progression, biomarkers, and treatment. Prospective in-person assessment can be costly and may be impossible for some patients. Remote assessment using mail and telephone contact may be a practical follow-up method. Patients enrolled in the multi-center Longitudinal and Biomarker Study in Parkinson's Disease (LABS-PD) in-person follow-up study in 2006 were invited to enroll in Follow-up of Persons With Neurologic Diseases (FOUND), which is overseen by a single center under a separate, central institutional review board protocol. FOUND uses mailed questionnaires and telephone interviews to assess PD status. FOUND follow-up continued when LABS-PD in-person visits ended in 2011. Retention and agreement between remote and in-person assessments were determined. In total, 422 of 499 (84.5%) of eligible patients volunteered, AND 96% of participants were retained. Of 60 patients who withdrew consent from LABS-PD, 51 were retained in FOUND. Of 341 patients who were active in LABS-PD, 340 were retained in FOUND (99.7%) when the in-person visits ceased. Exact agreement between remote and in-person assessments was 80% for diagnosis, disease features (eg, dyskinesias), and PD medication. Correlation between expert-rated and self-reported Unified Parkinson's Disease Rating Scale and Movement Disorder Society Unified Parkinson's Disease Rating Scale, which were examined at times separated by several months, was moderate or substantial for most items. Retention was excellent using remote follow-up of research participants with PD, providing a safety net when combined with in-person visits, and also is effective as a stand-alone assessment method, providing a useful alternative when in-person evaluation is not feasible. (c) 2014 International Parkinson and Movement Disorder Society C1 [Tanner, Caroline M.; Meng, Cheryl C.; Guest, Dolores D.; Fahn, Stanley] Parkinsons Inst, Sunnyvale, CA USA. [Tanner, Caroline M.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. [Ravina, Bernard] Biogen Idec Inc, Cambridge, MA USA. [Lang, Anthony] Univ Toronto, Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5S 1A1, Canada. [Kurlan, Roger] Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA. [Marek, Kenneth; Seibyl, John] Inst Neurodegenerat Disorders, New Haven, CT USA. [Oakes, David; Flagg, Emily; Kieburtz, Karl] Univ Rochester, Dept Neurol, Rochester, NY USA. [Gauger, Lisa] Duke Univ, Dept Neurol, Med Ctr, Durham, NC USA. [Goetz, Christopher G.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [DiEuliis, Diane] US Dept HHS, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA. Columbia Univ, Dept Neurol, New York, NY USA. [Elliott, Robin A.] Parkinsons Dis Fdn, New York, NY USA. [Shoulson, Ira] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. RP Tanner, CM (reprint author), San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, 4150 Clement St 127P, San Francisco, CA 94121 USA. EM ctannermd@aol.com FU Parkinson's Disease Foundation; National Institutes of Health; H. Lundbeck A/S; James Sharron Clark; Cephalon, Inc. FX This study was supported by the Parkinson's Disease Foundation; the National Institutes of Health; Cephalon, Inc.; H. Lundbeck A/S; and James & Sharron Clark. NR 40 TC 5 Z9 5 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2014 VL 29 IS 6 BP 743 EP 749 DI 10.1002/mds.25814 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AG4BI UT WOS:000335363300008 PM 24515275 ER PT J AU Cholerton, BA Zabetian, CP Wan, JY Montine, TJ Quinn, JF Mata, IF Chung, KA Peterson, A Espay, AJ Revilla, FJ Devoto, J Watson, GS Hu, SC Leverenz, JB Edwards, KL AF Cholerton, Brenna A. Zabetian, Cyrus P. Wan, Jia Y. Montine, Thomas J. Quinn, Joseph F. Mata, Ignacio F. Chung, Kathryn A. Peterson, Amie Espay, Alberto J. Revilla, Fredy J. Devoto, Johnna Watson, G. Stennis Hu, Shu-Ching Leverenz, James B. Edwards, Karen L. TI Evaluation of Mild Cognitive Impairment Subtypes in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson disease; cognition; mild cognitive impairment; neuropsychological assessment ID MINI-MENTAL-STATE; DIAGNOSTIC-CRITERIA; NORMATIVE DATA; DEMENTIA; TASK; ALZHEIMERS; CIRCUITRY; INCIDENT; DECLINE; COHORT AB Mild cognitive impairment in Parkinson's disease (PD-MCI) is common and increases the risk for dementia. Establishing distinct PD-MCI cognitive subtypes could be valuable for eventually predicting those most likely to convert to dementia. However, the study of PD-MCI subtypes has not yielded consistent results among cohorts. To determine whether there are distinct cognitive subtypes among participants diagnosed with PD-MCI in the Pacific Northwest Udall Center Clinical Consortium, we cognitively subtyped 95 patients with PD-MCI, using the Movement Disorders Society Task Force diagnostic guidelines. Psychometric test scores were then subjected to principle components factor analysis to determine whether similar cognitive subgroups could be identified using statistical methodology. Multiple-domain PD-MCI was diagnosed in 95% of the sample, and a range of cognitive impairments were noted. Factor analysis yielded seven factors and demonstrated overlap of phonemic verbal fluency on two factors, as well as the loading of verbal fluency on the same factor as a visuospatial measure; however, these factors did not partition the sample into distinct cognitive subtypes. Separation of cognitive subtypes based on the current PD-MCI criteria, or via statistical methods, may not provide sufficient information to describe distinct PD groups. Future efforts to validate the PD-MCI criteria and identify combinations of genetic or other risk factors for cognitive impairment are warranted. (c) 2014 International Parkinson and Movement Disorder Society C1 [Cholerton, Brenna A.; Zabetian, Cyrus P.; Mata, Ignacio F.; Leverenz, James B.] Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Cholerton, Brenna A.; Watson, G. Stennis; Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Zabetian, Cyrus P.; Hu, Shu-Ching; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Wan, Jia Y.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie] Portland VA Med Ctr, Portland, OR USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Revilla, Fredy J.] Cincinnati Veteran Affairs Med Ctr, Cincinnati, OH USA. RP Cholerton, BA (reprint author), VA Puget Sound Hlth Care Syst, GRECC A-182,9600 Vet Dr SW, Tacoma, WA 98493 USA. EM bchol@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306; Espay, Alberto/0000-0002-3389-136X FU Nancy and Buster Alvord Endowment; Department of Veterans Affairs; [NS065070]; [NS062684] FX This study was supported by NS062684 and NS065070, the Nancy and Buster Alvord Endowment, and the Department of Veterans Affairs. The funding sources did not provide scientific input for the study. NR 48 TC 16 Z9 16 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2014 VL 29 IS 6 BP 756 EP 764 DI 10.1002/mds.25875 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AG4BI UT WOS:000335363300010 PM 24710804 ER PT J AU Nuytemans, K Inchausti, V Beecham, GW Wang, LY Dickson, DW Trojanowski, JQ Lee, VMY Mash, DC Frosch, MP Foroud, TM Honig, LS Montine, TJ Dawson, TM Martin, ER Scott, WK Vance, JM AF Nuytemans, Karen Inchausti, Vanessa Beecham, Gary W. Wang, Liyong Dickson, Dennis W. Trojanowski, John Q. Lee, Virginia M. -Y. Mash, Deborah C. Frosch, Matthew P. Foroud, Tatiana M. Honig, Lawrence S. Montine, Thomas J. Dawson, Ted M. Martin, Eden R. Scott, William K. Vance, Jeffery M. TI Absence of C9ORF72 Expanded or Intermediate Repeats in Autopsy-Confirmed Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE autopsy confirmed; Parkinson's disease; C9ORF72 repeat; parkinsonism ID AMYOTROPHIC-LATERAL-SCLEROSIS; GGGGCC-HEXANUCLEOTIDE REPEAT; EXPANSIONS; PHENOTYPE; SPECTRUM; ALS; POPULATION; DISORDERS; COHORT; FTD AB BackgroundWe have reported that intermediate repeat lengths of the C9ORF72 repeat are a risk factor for Parkinson's disease (PD) in a clinically diagnosed data set. Because 10% to 25% of clinically diagnosed PD have different diagnoses upon autopsy, we hypothesized that this may reflect phenotypic heterogeneity or concomitant pathology of other neurodegenerative disorders. MethodsWe screened 488 autopsy-confirmed PD cases for expansion haplotype tag rs3849942T. In 196 identified haplotype carriers, the C9ORF72 repeat was genotyped using the repeat-primed polymerase chain reaction assay. ResultsNo larger (intermediate or expanded) repeats were found in these autopsy-confirmed PD samples. This absence of larger repeats is significantly different from the frequency in clinically diagnosed datasets (P=0.002). ConclusionsOur results suggest that expanded or intermediate C9ORF72 repeats in clinically diagnosed PD or parkinsonism might be an indication of heterogeneity in clinically diagnosed PD cases. Further studies are needed to elucidate the potential contribution of the C9ORF72 repeat to autopsy-confirmed PD. (c) 2014 International Parkinson and Movement Disorder Society C1 [Nuytemans, Karen; Inchausti, Vanessa; Beecham, Gary W.; Wang, Liyong; Martin, Eden R.; Scott, William K.; Vance, Jeffery M.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Beecham, Gary W.; Wang, Liyong; Martin, Eden R.; Scott, William K.; Vance, Jeffery M.] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USA. [Dickson, Dennis W.] Mayo Clin Florida, Dept Neurosci, Jacksonville, FL USA. [Trojanowski, John Q.; Lee, Virginia M. -Y.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA USA. [Mash, Deborah C.] Univ Miami, Miller Sch Med, Brain Endowment Bank, Miami, FL 33136 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Charlestown, MA USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Kubik Lab Neuropathol, Charlestown, MA USA. [Foroud, Tatiana M.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Honig, Lawrence S.] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA. [Honig, Lawrence S.] Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Inst Cell Engn, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. RP Vance, JM (reprint author), Univ Miami, Miller Sch Med, 1501 NW 10th Ave,Biomed Res Bldg,Suite 616, Miami, FL 33136 USA. EM jvance@med.miami.edu OI Dickson, Dennis W/0000-0001-7189-7917 FU NeuroBioBank [HHSN271201300028C]; JPB Foundation; [NS039764]; [NS071674]; [P50 NS072187]; [P50 AG016574]; [P50 NS053488]; [NS38377]; [P01 AG007232]; [AG06781]; [AG005136]; [NS062684]; [R01NS37167]; [P30AG10133]; [U24AG021886]; [P50 AG005134] FX This project was supported by NS039764 and NS071674 (to G. W. B., W. K. S., E. R. M., L. W., K.N., D. M. D., and J.M.V.), P50 NS072187 and P50 AG016574 (to D. W. D.), P50 NS053488 (to J.Q.T. and V.M.-Y.L.), NeuroBioBank HHSN271201300028C (to D. C. M.), NS38377 and the JPB Foundation (to T. M. D.), P01 AG007232 (to L. S. H.), AG06781, AG005136, and NS062684 (to T.J.M.), P01 AG007232 (to L. S. H.), R01NS37167, P30AG10133, and U24AG021886 (to T. F.), and P50 AG005134 and P50 NS038372 (to M.P.F.). NR 38 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2014 VL 29 IS 6 BP 827 EP 830 DI 10.1002/mds.25838 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AG4BI UT WOS:000335363300020 PM 24573903 ER PT J AU Green, AK Jacques, PF Rogers, G Fox, CS Meigs, JB McKeown, NM AF Green, Angela K. Jacques, Paul F. Rogers, Gail Fox, Caroline S. Meigs, James B. McKeown, Nicola M. TI Sugar-Sweetened Beverages and Prevalence of the Metabolically Abnormal Phenotype in the Framingham Heart Study SO OBESITY LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; INSULIN-RESISTANCE; HEALTHY OBESE; CARDIOVASCULAR-DISEASE; NORMAL-WEIGHT; AGED ADULTS; US ADULTS; RISK; CONSUMPTION; REPRODUCIBILITY AB Objective: The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories. Methods: The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Adults were classified as normal weight, overweight or obese and, within these categories, metabolic health was defined based on five criteria-hypertension, elevated fasting glucose, elevated triglycerides, low HDL cholesterol, and insulin resistance. Individuals without metabolic abnormalities were considered metabolically healthy. Logistic regression was used to examine the associations between categories of SSB consumption and risk of metabolic health after stratification by BMI. Results: Comparing the highest category of SSB consumers (median of 7 SSB per week) to the lowest category (non-consumers), odds ratios (95% confidence intervals) for metabolically abnormal phenotypes, compared to the metabolically normal, were 1.9 (1.1-3.4) among the obese, 2.0 (1.4-2.9) among the overweight, and 1.9 (1.4-2.6) among the normal weight individuals. Conclusions: In this cross-sectional analysis, it is observed that, irrespective of weight status, consumers of SSB were more likely to display metabolic abnormalities compared to non-consumers in a dosedependent manner. C1 [Green, Angela K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Jacques, Paul F.; Rogers, Gail; McKeown, Nicola M.] Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP McKeown, NM (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu FU National Heart Lung and Blood Institute [NO1-HC-25195]; USDA Agricultural Research Service [58-1950-0-014] FX This study was supported by grants from the National Heart Lung and Blood Institute (contract NO1-HC-25195) and the USDA Agricultural Research Service (agreement 58-1950-0-014). The funding providers did not play a role in any aspect of this study. NR 36 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAY PY 2014 VL 22 IS 5 BP E157 EP E163 DI 10.1002/oby.20724 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AH3OR UT WOS:000336034400024 PM 24550031 ER PT J AU Nguyen, J Fay, A Yadav, P MacIntosh, PW Metson, R AF John Nguyen Fay, Aaron Yadav, Prashant MacIntosh, Peter W. Metson, Ralph TI Stereotactic Microdebrider in Deep Lateral Orbital Decompression for Patients With Thyroid Eye Disease SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GRAVES OPHTHALMOPATHY; SURGERY; BONE; WALL; ORBITOPATHY; REMOVAL; NAVIGATION AB Purpose: Stereotactic navigation systems have been used in neurosurgery and otolaryngology with great success. The current investigation illustrates the novel use of a microdebrider with built-in stereotactic guidance in a series of thyroid orbitopathy patients who underwent deep lateral orbital wall decompression surgery. Methods: A noncomparative, interventional, retrospective case series of patients who underwent deep lateral deep orbital wall decompression from 2006 to 2013 was conducted in accordance with Institutional Review Board policy and the Declaration of Helsinki. Patient demographics, indications for surgery, pre-, intra-, and postoperative findings along with complications were recorded. Results: One hundred eight deep lateral orbital decompression surgeries were performed in 69 patients using the Straightshot M4 Microdebrider with built-in stereotactic guidance (Medtronics). Seventy-eight cases were in women and 30 cases were in men. The average age was 50.4 years (SD = 11.9 years). Indications for surgery included proptosis, exposure keratopathy, or compressive optic neuropathy. No patient experienced intraoperative complications. Specifically, cerebrospinal fluid leak, visual loss, infection, or unanticipated inflammation were not encountered. The average postoperative follow-up time was 5.35 months. Mean reduction in proptosis was 3.72 mm (SD = 2.1). Visual acuity improved in 32.4% (35/108) of cases. Conclusions: This surgical instrument combines a single handpiece locator, microdebrider, irrigator, retractor, and suction device into one. It enhances anatomical localization during orbital decompression and, with an integrated tissue guard, may decrease the risk of injury to orbital soft tissues. Stereotactic navigation enhances the surgeon's ability to determine the maximal limits of decompression in real time by confirming depth of bone removal and may potentially increase surgeons' confidence in orbital decompression surgery. C1 [John Nguyen] W Virginia Univ, Dept Ophthalmol, Morgantown, WV 26506 USA. [Fay, Aaron; Yadav, Prashant; MacIntosh, Peter W.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Fay, Aaron; Yadav, Prashant; MacIntosh, Peter W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 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 NR 28 TC 5 Z9 5 U1 0 U2 2 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 MAY-JUN PY 2014 VL 30 IS 3 BP 262 EP 266 DI 10.1097/IOP.0000000000000132 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AH2XX UT WOS:000335986500026 PM 24777260 ER PT J AU Gonzalez-Saldivar, G Lee, NG Chodosh, J Freitag, SK Stacy, RC AF Gonzalez-Saldivar, Gerardo Lee, N. Grace Chodosh, James Freitag, Suzanne K. Stacy, Rebecca C. TI Dacryops in the Setting of a Boston Type II Keratoprosthesis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Dacryops of the lacrimal tissue can develop under diverse circumstances. Recent evidence suggests that scarring or obstruction of the lacrimal ducts may lead to their dilatation and formation of a cystic structure. Patients who undergo repeated orbital surgery may therefore be at greater risk of dacryops formation. In this report, a patient who underwent multiple corneal and glaucoma procedures including Boston type II keratoprosthesis, after acid burns to both eyes, is described. Over time, a fluid-filled collection developed in the lower orbit. On surgical exploration and incision, fluid was drained from a cystic lesion which abutted the lacrimal gland and spanned the upper and lower orbits. The lesion was removed and was proven by histopathology and immunohistochemistry to be dacryops. This is the first known case of dacryops associated with Boston type II keratoprosthesis. C1 [Gonzalez-Saldivar, Gerardo] Univ Autonoma Nuevo Leon, Fac Med, Monterrey, Nuevo Leon, Mexico. [Lee, N. Grace; Chodosh, James; Freitag, Suzanne K.; Stacy, Rebecca C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Stacy, RC (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St,3rd Floor Pathol Lab, Boston, MA 02114 USA. EM Rebecca_Stacy@meei.harvard.edu NR 8 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 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2014 VL 30 IS 3 BP E73 EP E75 DI 10.1097/IOP.0b013e31829d0270 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AH2XX UT WOS:000335986500011 PM 24026001 ER PT J AU Higgins, DM Kerns, RD Brandt, CA Haskell, SG Bathulapalli, H Gilliam, W Goulet, JL AF Higgins, Diana M. Kerns, Robert D. Brandt, Cynthia A. Haskell, Sally G. Bathulapalli, Harini Gilliam, Wesley Goulet, Joseph L. TI Persistent Pain and Comorbidity Among Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans SO PAIN MEDICINE LA English DT Article DE Anxiety; Depression; Obesity; Pain Management; Persistent Pain; Post-traumatic Stress Syndrome; Substance Abuse ID LOW-BACK-PAIN; TRAUMATIC BRAIN-INJURY; POLYTRAUMA REHABILITATION; OLDER-ADULTS; VA USERS; HEALTH; CARE; PREVALENCE; DEPRESSION; DISORDERS AB ObjectiveChronic pain is a significant concern for the Veterans Health Administration (VHA), with chronic pain conditions among those most frequently reported by Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans. The current study examined VHA electronic medical record data to examine variation in demographics and high prevalence and high impact medical and mental health conditions in order to characterize the differences between patients with persistent pain and no pain. DesignA conservative operational definition of chronic or persistent pain based on multiple indicators of pain (i.e., pain intensity ratings, prescription opioids, pain clinic visits, International Classification of Diseases, Ninth Revision codes) was employed. Analyses included the entire roster of longitudinal clinical data on OEF/OIF/OND veterans who used VHA care to compare those with persistent pain with those with no clinical evidence of pain. ResultsResults of logistic regression models suggest that sex, race, education, military variables, body mass index (BMI), traumatic brain injury (TBI), and mental health conditions, but not age, reliably discriminate the two groups. Those with persistent pain were more likely to be Black, female, on active duty, enlisted, Army service members, have a high school education or less, and have diagnoses of mood disorders, post-traumatic stress disorder, substance use disorders, anxiety disorders, TBI, and have a BMI consistent with overweight and obesity. ConclusionsThe operational definition of chronic pain used in this study may have research implications for examining predictors of incident and chronic pain. These data have important clinical implications in that addressing comorbid conditions of persistent pain may improve adaptive coping and functioning in these patients. C1 [Higgins, Diana M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Higgins, Diana M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kerns, Robert D.; Brandt, Cynthia A.; Haskell, Sally G.; Goulet, Joseph L.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Kerns, Robert D.; Brandt, Cynthia A.; Haskell, Sally G.; Bathulapalli, Harini; Goulet, Joseph L.] Yale Univ, Sch Med, New Haven, CT USA. RP Higgins, DM (reprint author), VA Boston Healthcare Syst, Res Serv Psychol Serv 116B-2,150 South Huntington, Boston, MA 02130 USA. EM diana.higgins2@va.gov RI Bathulapalli, Harini/B-7451-2015; OI Goulet, Joseph/0000-0002-0842-804X FU VA Health Services Research and Development award [DHI07-065] FX This research was supported by a VA Health Services Research and Development award (PI: SH & CB), #DHI07-065. NR 33 TC 24 Z9 24 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD MAY PY 2014 VL 15 IS 5 BP 782 EP 790 DI 10.1111/pme.12388 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AH9JS UT WOS:000336458900011 PM 24548466 ER PT J AU Bagatell, R Norris, R Ingle, AM Ahern, C Voss, S Fox, E Little, AR Weigel, BJ Adamson, PC Blaney, S AF Bagatell, Rochelle Norris, Robin Ingle, Ashish M. Ahern, Charlotte Voss, Stephan Fox, Elizabeth Little, Anthony R. Weigel, Brenda J. Adamson, Peter C. Blaney, Susan TI Phase 1 Trial of Temsirolimus in Combination with Irinotecan and Temozolomide in Children, Adolescents and Young Adults with Relapsed or Refractory Solid Tumors: A Children's Oncology Group Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE phase 1; solid tumors; temsirolimus ID RENAL-CELL CARCINOMA; MAMMALIAN TARGET; RAPAMYCIN; MTOR; RHABDOMYOSARCOMA; CANCER; EVEROLIMUS; GROWTH; NEUROBLASTOMA; INHIBITION AB BackgroundmTOR inhibitors have activity in pediatric tumor models. A phase I trial of the mTOR inhibitor temsirolimus (TEM) with irinotecan (IRN) and temozolomide (TMZ) was conducted in children with recurrent/refractory solid tumors, including central nervous system (CNS) tumors. MethodsEscalating doses of intravenous (IV) TEM were administered on days 1 and 8 of 21-day cycles. IRN (50mg/m(2)/dose escalated to a maximum of 90mg/m(2)/dose) and TMZ (100mg/m(2)/dose escalated to a maximum of 150mg/m(2)/dose) were administered orally (PO) on days 1-5. When maximum tolerated doses (MTD) were identified, TEM frequency was increased to weekly. ResultsSeventy-one eligible pts (median age 10.9 years, range 1.0-21.5) with neuroblastoma (16), osteosarcoma (7), Ewing sarcoma (7), rhabdomyosarcoma (4), CNS (22) or other (15) tumors were enrolled. Dose-limiting hyperlipidemia occurred in two patients receiving oral corticosteroids. The protocol was subsequently amended to preclude chronic steroid use. The MTD was identified as TEM 35mg/m(2) IV weekly, with IRN 90mg/m(2) and TMZ 125mg/m(2) PO on days 1-5. At higher dose levels, elevated serum alanine aminotransferase and triglycerides, anorexia, and thrombocytopenia were dose limiting. Additional grade 3 regimen-related toxicities included leukopenia, neutropenia, lymphopenia, anemia, and nausea/vomiting. Six patients had objective responses confirmed by central review; three of these had sustained responses through 14 cycles of therapy. ConclusionThe combination of TEM (35mg/m(2)/dose IV weekly), IRN (90mg/m(2)/dose days 1-5) and TMZ (125mg/m(2)/dose days 1-5) administered PO every 21 days is well tolerated in children. Phase 2 trials of this combination are ongoing. Pediatr Blood Cancer 2014;61:833-839. (c) 2013 Wiley Periodicals, Inc. C1 [Bagatell, Rochelle; Fox, Elizabeth; Little, Anthony R.; Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Norris, Robin] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Ingle, Ashish M.] Childrens Oncol Grp Stat & Data Ctr, Arcadia, CA USA. [Ahern, Charlotte; Blaney, Susan] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Voss, Stephan] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. [Weigel, Brenda J.] Univ Minnesota, Minneapolis, MN USA. RP Bagatell, R (reprint author), Childrens Hosp Philadelphia, CTRB 4022,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bagatellr@email.chop.edu FU NCI NIH HHS [U10 CA098543, U10 CA098413, UM1 CA097452, U01 CA097452] NR 32 TC 21 Z9 21 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 IS 5 BP 833 EP 839 DI 10.1002/pbc.24874 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AD7ZI UT WOS:000333485600012 PM 24249672 ER PT J AU Kassam, A Skiadaresis, J Alexander, S Wolfe, J AF Kassam, Alisha Skiadaresis, Julia Alexander, Sarah Wolfe, Joanne TI Parent and Clinician Preferences for Location of End-of-Life Care: Home, Hospital or Freestanding Hospice? SO PEDIATRIC BLOOD & CANCER LA English DT Article DE palliative care; end of life care; paediatric oncology; quality of life ID PALLIATIVE CARE; CANCER-PATIENTS; CHILDREN; DEATH; PLACE; DIE; DETERMINANTS; PERSPECTIVES AB BackgroundCurrent options for location of end-of-life (EOL) care for children with cancer include home, hospital, and freestanding pediatric hospice (FSPH). However, access to these options varies greatly depending on geographical location. We aimed to determine bereaved parent and clinician preferences for location to EOL care and death. ProcedureWe administered questionnaires to 75 bereaved parents (response rate 54%) and 48 pediatric oncology clinicians (response rate 91%) at a large teaching hospital. Main outcome measure was parent and clinician ranking for preferred location of EOL care and death if given the options of home, hospital or FSPH. ResultsMajority of parents and clinicians ranked home as their first choice for EOL care (70.2% and 87%, respectively) and death (70.8% and 89.1%, respectively). Compared to clinicians, parents gave a higher ranking to hospital (P<0.01) and lower ranking to FSPH (P<0.01) as the preferred location for EOL care and death. Congruence between actual and preferred location of EOL care was more likely when a palliative care team was involved (P<0.01) and less likely for children with haematologic malignancies (P=0.03). ConclusionsParents and clinicians prefer home as the location for EOL care and death for children with cancer. Hospital based palliative care is a preferred alternative if home is not desired. FSPH is a relatively recent phenomena and further research needs to be directed towards understanding its cost benefit in comparison to home and hospital-based EOL care. Pediatr Blood Cancer 2014;61:859-864. (c) 2013 Wiley Periodicals, Inc. C1 [Kassam, Alisha] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Kassam, Alisha] Southlake Reg Hlth Ctr, Dept Med, Div Palliat Med, Newmarket, ON, Canada. [Skiadaresis, Julia] Univ Toronto, Fac Social Work, Toronto, ON M5S 1A1, Canada. [Alexander, Sarah] Univ Toronto, Hosp Sick Children, Dept Paediat, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada. [Wolfe, Joanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Wolfe, Joanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Wolfe, Joanne] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. RP Wolfe, J (reprint author), Paediat Palliat Care Childrens Hosp Boston, Dept Psychosocial Oncol & Palliat Care, Paediat Palliat Care Serv, Div Chief,Dana Farber Canc Inst, Dana 2012,450 Brookline Ave, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu FU Paediatric Oncology Group of Ontario FX Grant sponsor: Paediatric Oncology Group of Ontario NR 25 TC 20 Z9 20 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 IS 5 BP 859 EP 864 DI 10.1002/pbc.24872 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AD7ZI UT WOS:000333485600017 PM 24265171 ER PT J AU Williams, DA Bennett, C Bertuch, A Bessler, M Coates, T Corey, S Dror, Y Huang, J Lipton, J Olson, TS Reiss, UM Rogers, ZR Sieff, C Vlachos, A Walkovich, K Wang, W Shimamura, A AF Williams, David A. Bennett, Carolyn Bertuch, Alison Bessler, Monica Coates, Thomas Corey, Seth Dror, Yigal Huang, James Lipton, Jeffrey Olson, Timothy S. Reiss, Ulrike M. Rogers, Zora R. Sieff, Colin Vlachos, Adrianna Walkovich, Kelly Wang, Winfred Shimamura, Akiko TI Diagnosis and Treatment of Pediatric Acquired Aplastic Anemia (AAA): An Initial Survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC) SO PEDIATRIC BLOOD & CANCER LA English DT Article DE acquired aplastic anemia; diagnosis; NAPAAC; treatment ID IMMUNOSUPPRESSIVE THERAPY; ANTITHYMOCYTE GLOBULIN; STIMULATING FACTOR; CHILDREN; EPIDEMIOLOGY; CHILDHOOD; TRANSPLANTATION; CYCLOSPORINE; MULTICENTER; EXPERIENCE AB BackgroundRandomized clinical trials in pediatric aplastic anemia (AA) are rare and data to guide standards of care are scarce. ProcedureEighteen pediatric institutions formed the North American Pediatric Aplastic Anemia Consortium to foster collaborative studies in AA. The initial goal of NAPAAC was to survey the diagnostic studies and therapies utilized in AA. ResultsOur survey indicates considerable variability among institutions in the diagnosis and treatment of AA. There were areas of general consensus, including the need for a bone marrow evaluation, cytogenetic and specific fluorescent in situ hybridization assays to establish diagnosis and exclude genetic etiologies with many institutions requiring results prior to initiation of immunosuppressive therapy (IST); uniform referral for hematopoietic stem cell transplantation as first line therapy if an HLA-identical sibling is identified; the use of first-line IST containing horse anti-thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling donor is not identified; supportive care measures; and slow taper of CSA after response. Areas of controversy included the need for telomere length results prior to IST, the time after IST initiation defining a treatment failure; use of hematopoietic growth factors; the preferred rescue therapy after failure of IST; the use of specific hemoglobin and platelet levels as triggers for transfusion support; the use of prophylactic antibiotics; and follow-up monitoring after completion of treatment. ConclusionsThese initial survey results reflect heterogeneity in diagnosis and care amongst pediatric centers and emphasize the need to develop evidence-based diagnosis and treatment approaches in this rare disease. Pediatr Blood Cancer 2014;61:869-874. (c) 2013 Wiley Periodicals, Inc. C1 [Williams, David A.; Sieff, Colin] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Williams, David A.; Sieff, Colin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bennett, Carolyn] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA. [Bertuch, Alison] Texas Childrens Hosp, Houston, TX 77030 USA. [Bertuch, Alison] Baylor Coll Med, Houston, TX 77030 USA. [Bessler, Monica; Olson, Timothy S.] Childrens Hosp Philadelphia, Comprehens Bone Marrow Failure Ctr, Div Hematol, Dept Pediat, Philadelphia, PA 19104 USA. [Bessler, Monica; Olson, Timothy S.] Univ Penn, Dept Med, Div Hematooncol, Perlman Sch Med, Philadelphia, PA 19104 USA. [Coates, Thomas] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Corey, Seth] Lurie Childrens Hosp Chicago, Div Hematol Oncol, Chicago, IL USA. [Dror, Yigal] Univ Toronto, Hosp Sick Children, Genet & Genome Biol Program, Res Inst, Toronto, ON M5G 1X8, Canada. [Dror, Yigal] Univ Toronto, Hosp Sick Children, Marrow Failure & Myelodysplasia Program, Div Hematol Oncol,Dept Pediat, Toronto, ON M5G 1X8, Canada. [Huang, James] Univ Calif San Francisco, Dept Pediat, Div Pediat Hematol Oncol, San Francisco, CA USA. [Huang, James] Benioff Childrens Hosp, San Francisco, CA USA. [Lipton, Jeffrey; Vlachos, Adrianna] Cohen Childrens Med Ctr New York, New Hyde Pk, NY USA. [Lipton, Jeffrey; Vlachos, Adrianna] Feinstein Inst Med Res, Manhasset, NY USA. [Reiss, Ulrike M.; Wang, Winfred] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. [Rogers, Zora R.] Univ Texas Southwestern, Dallas, TX USA. [Walkovich, Kelly] Univ Michigan, Div Hematol Oncol, Dept Pediat & Communicable Dis, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Shimamura, Akiko] Fred Hutchison Canc Res Ctr, Seattle, WA USA. [Shimamura, Akiko] Seattle Childrens Hosp, Seattle, WA USA. RP Williams, DA (reprint author), 1 Blackfan Circle,Karp 08125, Boston, MA 02115 USA. EM david.williams2@childrens.harvard.edu OI Coates, Thomas/0000-0001-9878-6029 FU NCI NIH HHS [P30 CA016520]; NHLBI NIH HHS [K12 HL087064, K08 HL122306] NR 22 TC 5 Z9 8 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 IS 5 BP 869 EP 874 DI 10.1002/pbc.24875 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AD7ZI UT WOS:000333485600019 PM 24285674 ER PT J AU Vrooman, L Blonquist, T Neuberg, D Athale, U Clavell, L Kelly, K Laverdiere, C Michon, B Place, A Welch, J Sallan, S Silverman, L AF Vrooman, Lynda Blonquist, Traci Neuberg, Donna Athale, Uma Clavell, Luis Kelly, Kara Laverdiere, Caroline Michon, Bruno Place, Andrew Welch, Jennifer Sallan, Stephen Silverman, Lewis TI HEALTH-RELATED QUALITY OF LIFE ASSESSMENT IN CHILDREN AND ADOLESCENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL): A REPORT FROM DANA-FARBER CANCER INSTITUTE (DFCI) ALL CONSORTIUM PROTOCOL 05-001 SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Vrooman, Lynda; Blonquist, Traci; Neuberg, Donna; Athale, Uma; Clavell, Luis; Kelly, Kara; Laverdiere, Caroline; Michon, Bruno; Place, Andrew; Welch, Jennifer; Sallan, Stephen; Silverman, Lewis] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 SU 1 SI SI BP S85 EP S85 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG5WT UT WOS:000335490100296 ER PT J AU Blume, ED Balkin, EM Aiyagari, R Ziniel, S Beke, DM Thiagarajan, R Taylor, L Kulik, T Pituch, K Wolfe, J AF Blume, Elizabeth D. Balkin, Emily Morell Aiyagari, Ranjit Ziniel, Sonja Beke, Dorothy M. Thiagarajan, Ravi Taylor, Laura Kulik, Thomas Pituch, Kenneth Wolfe, Joanne TI Parental Perspectives on Suffering and Quality of Life at End-of-Life in Children With Advanced Heart Disease: An Exploratory Study SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE echocardiography; pediatric intensive care; clinical outcomes; pediatric cardiology; pediatric; diagnostic utility ID INTENSIVE-CARE-UNIT; PALLIATIVE CARE; CANCER AB Objectives: Although transthoracic echocardiography is commonly performed in the PICU, its utility is not specifically known. The purpose of this investigation was to evaluate the clinical impact of echocardiography in the PICU in terms of frequency of unanticipated findings and the frequency and nature of clinical management changes attributed to the results of echocardiography. Design: Prospective cohort study. Setting: Nineteen-bed combined medical-surgical-cardiac PICU at a tertiary care children's hospital. Patients: All patients in PICU undergoing transthoracic echocardiography. Interventions < span class="punctuation">< span class="punctuation">, Measurements < span class="punctuation">< span class="punctuation">, and Main Results: Data collected included echocardiography indications, pre-echocardiography clinical assessment of anticipated echocardiography findings, height, weight, primary diagnosis, age, and urgency (stat vs routine) of echocardiography. Input of the attending care team (intensivist, cardiologist, and/or cardiovascular surgeon) allowed classification of echocardiography results as either confirming the pre-echocardiography impression, altering the pre-echocardiography clinical impression regarding the indication for which the test was performed, or altering the impression by virtue of new findings unrelated to the specific indication. The nature of the new findings were recorded and categorized. The team recorded clinical management changes made in response to the echocardiography results; the nature of these were listed and categorized. Echocardiograms (n = 416) were performed in 132 patients. Of these, 244 echocardiograms (59%) were ordered on male patients, 31% were under 30 days old, median age was 103 days, 379 (91%) had a primary cardiac diagnosis, and 92 (22%) were ordered stat. Sixty-three percent of echocardiograms confirmed and 24% altered the pre-echocardiography impression regarding the indication for the echocardiography; 13% introduced new findings unrelated to the indication. Cardiac surgical revision was the management change required in 26 patients (6.3%). Stat echocardiography was more likely to alter the pre-echocardiography assessment than routine echocardiography (p < 0.001). Management changes were more commonly associated with stat echocardiograms (p = 0.002) and those with new unexpected findings (p < 0.001) but had no demonstrable association with age less than 30 days (p = 0.332). Conclusions: Unanticipated echocardiography results are common in the PICU, and they often alter the clinical impressions that prompted the echocardiogram or introduce new findings unrelated to the reason for which the echocardiogram was recorded. Clinical management changes attributable to echocardiography findings are frequent in the PICU, including occasional surgical intervention. Echocardiography adds diagnostic value and contributes to the management approach in the PICU, accounting for its frequent use. C1 [Blume, Elizabeth D.; Balkin, Emily Morell; Beke, Dorothy M.; Thiagarajan, Ravi; Kulik, Thomas] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Aiyagari, Ranjit; Taylor, Laura; Pituch, Kenneth] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Ziniel, Sonja] Boston Childrens Hosp, Dept Adolescent Med, Boston, MA USA. [Ziniel, Sonja] Boston Childrens Hosp, Program Patient Safety & Qual, Boston, MA USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Blume, ED (reprint author), Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. EM elizabeth.blume@cardio.chboston.org FU Kara Duclos Family Fund; Heart Transplant Research and Education Fund at Boston Children's Hospital; Transplant Education and Research Fund; Kara Duclos Fund FX Supported, in part, by the Kara Duclos Family Fund and the Heart Transplant Research and Education Fund at Boston Children's Hospital.; Dr. Blume received grant support (family of the patient donated $5,000 for mailing costs and statistical support associated with the project) and received provision of writing assistance from the Transplant Education and Research Fund and the Kara Duclos Fund. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 18 TC 14 Z9 14 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAY PY 2014 VL 15 IS 4 BP 336 EP 342 DI 10.1097/PCC.0000000000000099 PG 7 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA AG7CZ UT WOS:000335576900012 PM 24583501 ER PT J AU Gulur, P El Saleeby, C Watt, LD Koury, KM Cohen, AR AF Gulur, Padma El Saleeby, Chadi Watt, Lisa D. Koury, Katharine M. Cohen, Ari R. TI Elevated Lidocaine Serum Levels Following the Use of a Needle Free Device in Healthy Adult Volunteers SO PEDIATRIC EMERGENCY CARE LA English DT Article DE lidocaine toxicity; elevated serum levels; systemic circulation; lidocaine; needle-free device ID PHARMACOKINETICS AB There is increased concern regarding circulating levels of lidocaine immediately after the use of a needle-free device with buffered lidocaine. As a result, we conducted a prospective study to assess lidocaine circulation after the use of a needle-free device for the delivery of a local anesthetic in 10 healthy adult subjects. After informed consent, 2 peripheral intravenous catheters were placed in the antecubital fossa of each arm. Two milligrams of 1% buffered lidocaine was administered by the study physician via the needle-free device on the dorsum of the subject's hand. Within 2 minutes, a third intravenous catheter was placed in the location of the lidocaine administration and 5 mL of blood was collected from all 3 sites. If blood samples returned positive for lidocaine, they were also collected 1 hour and 2 hours after administration. Toxic levels of lidocaine were found in blood drawn from 2 subjects immediately after lidocaine administration. Results also showed that certain subjects had increasing levels of lidocaine over time. Other subjects also had increasing lidocaine serum levels from blood drawn on the arm opposite the administration site. We concluded that there may be systemic lidocaine levels with the administration of the needle-free device and that these levels may reach the toxic range in adults. Further investigation will be required to determine whether this finding has clinical significance, especially considering the smaller body mass of children. C1 [Gulur, Padma; Watt, Lisa D.; Koury, Katharine M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gulur, Padma; El Saleeby, Chadi; Cohen, Ari R.] Harvard Univ, Sch Med, Boston, MA USA. [El Saleeby, Chadi] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Cohen, Ari R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 15 Parkman St,WACC330, Boston, MA 02114 USA. EM pgulur@yahoo.com NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 EI 1535-1815 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD MAY PY 2014 VL 30 IS 5 BP 335 EP 339 DI 10.1097/PEC.0000000000000125 PG 5 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA AG9ON UT WOS:000335749100008 PM 24786988 ER PT J AU Boeke, CE Tamimi, RM Berkey, CS Colditz, GA Eliassen, AH Malspeis, S Willett, WC Frazier, AL AF Boeke, Caroline E. Tamimi, Rulla M. Berkey, Catherine S. Colditz, Graham A. Eliassen, A. Heather Malspeis, Susan Willett, Walter C. Frazier, A. Lindsay TI Adolescent Carotenoid Intake and Benign Breast Disease SO PEDIATRICS LA English DT Article DE cancer; adolescent health; diet; vitamin A; breast ID FOOD FREQUENCY QUESTIONNAIRE; YOUNG-WOMEN; CANCER-RISK; PROSPECTIVE COHORT; POOLED ANALYSIS; BETA-CAROTENE; VITAMIN-A; METAANALYSIS; REPRODUCIBILITY; PROLIFERATION AB BACKGROUND:Carotenoids may reduce risk of benign breast disease (BBD), an independent risk factor for breast cancer, through antioxidative or antiproliferative mechanisms. Exposure to carotenoids may be most important during adolescence when breast tissue is still developing. We examined adolescent carotenoid intake in relation to BBD in young women.METHODS:In 6593 adolescent girls in the prospective Growing Up Today Study cohort, intakes of -carotene, -carotene, -cryptoxanthin, lutein/zeaxanthin, and lycopene were assessed by using the means from food-frequency questionnaires in 1996, 1997, and 1998. Girls reported biopsy-confirmed BBD on questionnaires in 2005, 2007, and 2010 (n = 122). We conducted logistic regression of energy-adjusted carotenoid intakes in relation to BBD, adjusted for age, family history of breast cancer or BBD, age at menarche, nulliparity, alcohol intake, BMI, and physical activity.RESULTS:Mean (SD) age at baseline was 12.0 (1.6) years. -Carotene intake was inversely associated with BBD; comparing the highest to lowest quartile, the multivariate-adjusted odds ratio was 0.58 (95% confidence interval: 0.34-1.00; P-trend = .03). -Carotene and lutein/zeaxanthin were also inversely associated with BBD, but the associations were not statistically significant.CONCLUSIONS:Adolescent carotenoid intake may be associated with lower BBD risk; these findings warrant further study. C1 [Boeke, Caroline E.; Tamimi, Rulla M.; Eliassen, A. Heather; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Boeke, Caroline E.; Tamimi, Rulla M.; Berkey, Catherine S.; Eliassen, A. Heather; Malspeis, Susan; Willett, Walter C.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Tamimi, Rulla M.; Berkey, Catherine S.; Eliassen, A. Heather; Willett, Walter C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Boeke, CE (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM caroline.boeke@mail.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU National Institutes of Health [R01 DK084001, UM1 CA176726, CA 050385]; Breast Cancer Research Foundation; American Institute for Cancer Research; National Institutes of Health (NIH); [T32 CA 09001] FX Funded by National Institutes of Health grants R01 DK084001, UM1 CA176726, and CA 050385 as well as the Breast Cancer Research Foundation. Dr Boeke was funded by T32 CA 09001. Dr Frazier was supported by an award from the American Institute for Cancer Research. Funded by the National Institutes of Health (NIH). NR 29 TC 5 Z9 5 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2014 VL 133 IS 5 BP E1292 EP E1298 DI 10.1542/peds.2013-3844 PG 7 WC Pediatrics SC Pediatrics GA AG2HK UT WOS:000335236800051 PM 24709924 ER PT J AU Raffetto, JD AF Raffetto, Joseph D. TI Which dressings reduce inflammation and improve venous leg ulcer healing SO PHLEBOLOGY LA English DT Review DE Venous leg ulcer; inflammation; venous hypertension; wound care; leukocytes; macrophage; fibroblasts; adhesions molecules; selectins; chemokines; growth factors; proteases; proteinases; matrix metalloproteinases; compression; biologic skin substitutes; extracellular matrix ID RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; COMPRESSION THERAPY; LOCAL-MANAGEMENT; MATRIX; KERATINOCYTES; INSUFFICIENCY; FIBROBLASTS; GUIDELINES; EFFICACY AB Chronic venous leg ulcers (VLU) affect around 1% of the adult population in the Western world. The impact of VLU is both social and economic, with significant expenditures on active venous ulcers to provide medical treatment and eventual healing. At the core of VLU is venous hypertension which affects the venous macrocirculation. The changes incurred in venous hemodynamics leads to microcirculatory changes affecting the postcapillary venule and surrounding tissues. Inflammation by leukocytes affecting the venous endothelium, promotes a complex cascade and activation of adhesion molecules expression, chemokines and cytokines released, altered growth factor responses, and activation of protease (e.g. tPA) and proteinase (e.g. MMPs) activity that causes dysregulation and compromise of tissue integrity with eventual dermal damage and ulcer development. A critical component to treating VLU is correcting the abnormal venous hemodynamics and compression therapy. Unfortunately, VLU recurrence ranges between 30-70%, and other modalities in therapy along with compression are required. The goal for adjuvant products is to restore the balance from an inflammatory chronic wound to that of a reparative wound that will promote provisional matrix and epithelialization. There are many products on the market that can be used as adjuvant to compression therapy, but it must be recognized that there is a paucity of clinical trials that have evaluated the clinical effectiveness of specific products with clearly defined end points, and most importantly a healed VLU with a low recurrence rate. This review will discuss the fundamentals of VLU inflammation, and evaluate the available literature that may have benefit in reducing inflammation and lead to effective VLU healing. C1 [Raffetto, Joseph D.] VA Boston Healthcare Syst, Div Vasc Surg, West Roxbury, MA USA. [Raffetto, Joseph D.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Raffetto, Joseph D.] Harvard Univ, Sch Med, Boston, MA USA. RP Raffetto, JD (reprint author), VA Boston, HCS Surg, 112 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov NR 35 TC 4 Z9 4 U1 1 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0268-3555 EI 1758-1125 J9 PHLEBOLOGY JI Phlebology PD MAY PY 2014 VL 29 SU 1 BP 157 EP 164 DI 10.1177/0268355514529225 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AH6TA UT WOS:000336262400026 PM 24843103 ER PT J AU Meffert, SM Abdo, AO Abd Alla, OA Elmakki, YOM Omer, AA Yousif, S Metzler, TJ Marmar, CR AF Meffert, Susan M. Abdo, Akram Osman Abd Alla, Omayma Ahmed Elmakki, Yasir Omer Mustafa Omer, Afrah Abdelrahim Yousif, Sahar Metzler, Thomas J. Marmar, Charles R. TI A Pilot Randomized Controlled Trial of Interpersonal Psychotherapy for Sudanese Refugees in Cairo, Egypt SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE refugee; Sudan; global mental health; PTSD; depression; violence ID POSTTRAUMATIC-STRESS-DISORDER; WORLD-TRADE-CENTER; SOCIAL SUPPORT; VIETNAM VETERANS; TRAUMATIC STRESS; MENTAL-HEALTH; RURAL UGANDA; RISK-FACTORS; ATTACHMENT; DEPRESSION AB Approximately one third of a population exposed to mass violence develops posttraumatic stress disorder (PTSD) and approximately half develops depression, yet little is known about how to effectively treat these populations. This study's objective was to examine the impact of interpersonal psychotherapy (IPT) on Sudanese refugees living in Cairo, Egypt, who had symptoms of PTSD. A randomized controlled trial (April-August 2008) with 22 Sudanese refugees in Cairo, Egypt, tested two hypotheses: (1) After IPT, participants will have fewer symptoms of depression and PTSD compared with waitlist controls. (2) After IPT, participants will have less interpersonal violence compared with waitlist controls. Participants were randomly assigned to either 6 sessions of IPT delivered by Sudanese community therapists without previous mental health training or a waitlist control group. Measures taken at baseline and trial conclusion included the Harvard Trauma Questionnaire, the Beck Depression Index-II, the Conflict Tactics Scale, and the State-Trait Anger Inventory, all translated and adapted for local use. The effect sizes of IPT treatment for PTSD symptoms, depression, state anger, trait anger, and Conflict Tactics Scale-Violence Toward Household were -2.52, -2.38, -1.21, -1.43, and -0.84, respectively. IPT predicted a significant decrease in symptoms of PTSD, state anger, and depression using a conservative intent-to-treat analysis. This study represents the first randomized controlled trial of IPT to address PTSD, depression, and interpersonal violence in a refugee population. The study's preliminary success has positive implications for development of effective and sustainable mental health interventions to support the recovery of traumatized populations. C1 [Meffert, Susan M.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Abdo, Akram Osman; Abd Alla, Omayma Ahmed; Elmakki, Yasir Omer Mustafa; Omer, Afrah Abdelrahim; Yousif, Sahar] Maan Org, Cairo, Egypt. [Abd Alla, Omayma Ahmed] St Andrews United Church Cairo, Cairo, Egypt. [Metzler, Thomas J.] San Francisco Vet Adm Med Ctr, Mental Hlth Serv, San Francisco, CA USA. RP Meffert, SM (reprint author), 50 Beale St,Suite 1200,Box 1224, San Francisco, CA 94105 USA. EM SusanM@lppi.uscf.edu NR 55 TC 5 Z9 5 U1 8 U2 21 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAY PY 2014 VL 6 IS 3 BP 240 EP 249 DI 10.1037/a0023540 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AH4FC UT WOS:000336081500007 ER PT J AU Nickels, PC Ke, YG Jungmann, R Smith, DM Leichsenring, M Shih, WM Liedl, T Hogberg, B AF Nickels, Philipp C. Ke, Yonggang Jungmann, Ralf Smith, David M. Leichsenring, Marc Shih, William M. Liedl, Tim Hogberg, Bjorn TI DNA Origami Structures Directly Assembled from Intact Bacteriophages SO SMALL LA English DT Article DE DNA nanotechnology; DNA origami; DNA structures; self-assembly; bacteriophage ID NANOSCALE SHAPES; FOLDING DNA; NANOSTRUCTURES; SCAFFOLD; TILES C1 [Jungmann, Ralf; Smith, David M.; Shih, William M.] Univ Munich, Dept Phys, D-80539 Munich, Germany. [Jungmann, Ralf; Smith, David M.; Shih, William M.] Univ Munich, Ctr Nanosci CeNS, D-80539 Munich, Germany. [Liedl, Tim] Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, S-17177 Stockholm, Sweden. [Nickels, Philipp C.; Ke, Yonggang; Leichsenring, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liedl, T (reprint author), Univ Munich, Dept Phys, Geschwister Scholl Pl 1, D-80539 Munich, Germany. EM tim.liedl@physik.lmu.de; bjorn.hogberg@ki.se RI Jungmann, Ralf/A-6357-2015; OI Jungmann, Ralf/0000-0003-4607-3312; /0000-0002-7455-3359; Liedl, Tim/0000-0002-0040-0173; Hogberg, Bjorn/0000-0003-2715-7887 FU NIH [1DP2OD004641-01]; Swedish Research Council [2010-6296, 2010-5060]; Deutsche Forschungsgemeinschaft DFG [TI 329/5-1]; Carl Bennet AB; Karolinska Institutet; Vinnova FX We thank J. Wohrstein for help with pipetting, S. Kempter for experimental support and S. Douglas, H. HOiberg and R. Schreiber for helpful discussions. This work was funded by a NIH New Investigator grant (1DP2OD004641-01) to W.M.S., the Swedish Research Council (Vetenskapsradet) through a repatriation grant and a project grant to B.H. (grants 2010-6296 and 2010-5060) and the Deutsche Forschungsgemeinschaft DFG (TI 329/5-1). B.H. is a recipient of an assistant professorship with startup funding by Carl Bennet AB, Karolinska Institutet and Vinnova. NR 30 TC 11 Z9 11 U1 7 U2 47 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 EI 1613-6829 J9 SMALL JI Small PD MAY PY 2014 VL 10 IS 9 BP 1765 EP 1769 DI 10.1002/smll.201303442 PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AG7BR UT WOS:000335573500015 PM 24532395 ER PT J AU Moriguchi, Y Touroutoglou, A Dickerson, BC Barrett, LF AF Moriguchi, Yoshiya Touroutoglou, Alexandra Dickerson, Bradford C. Barrett, Lisa Feldman TI Sex differences in the neural correlates of affective experience SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE anterior insula; anterior cingulate; interoceptive; extraceptive; fMRI ID EMOTIONALLY INFLUENCED MEMORY; GENDER-DIFFERENCES; ASPERGER-SYNDROME; VISUAL-CORTEX; HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; AMYGDALA RESPONSE; IMMEDIATE MEMORY; INSULAR CORTEX; SELF-REPORT AB People believe that women are more emotionally intense than men, but the scientific evidence is equivocal. In this study, we tested the novel hypothesis that men and women differ in the neural correlates of affective experience, rather than in the intensity of neural activity, with women being more internally (interoceptively) focused and men being more externally (visually) focused. Adult men (n = 17) and women (n = 17) completed a functional magnetic resonance imaging study while viewing affectively potent images and rating their moment-to-moment feelings of subjective arousal. We found that men and women do not differ overall in their intensity of moment-to-moment affective experiences when viewing evocative images, but instead, as predicted, women showed a greater association between the momentary arousal ratings and neural responses in the anterior insula cortex, which represents bodily sensations, whereas men showed stronger correlations between their momentary arousal ratings and neural responses in the visual cortex. Men also showed enhanced functional connectivity between the dorsal anterior insula cortex and the dorsal anterior cingulate cortex, which constitutes the circuitry involved with regulating shifts of attention to the world. These results demonstrate that the same affective experience is realized differently in different people, such that women's feelings are relatively more self-focused, whereas men's feelings are relatively more world-focused. C1 [Moriguchi, Yoshiya] Natl Ctr Neurol & Psychiat, Dept Psychophysiol, Natl Inst Mental Hlth, Kodaira, Tokyo 1870031, Japan. [Moriguchi, Yoshiya] Natl Ctr Neurol & Psychiat, Integrat Brain Imaging Ctr, Kodaira, Tokyo 1870031, Japan. [Moriguchi, Yoshiya; Touroutoglou, Alexandra; Dickerson, Bradford C.; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Moriguchi, Yoshiya; Touroutoglou, Alexandra; Dickerson, Bradford C.; Barrett, Lisa Feldman] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Touroutoglou, Alexandra; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Moriguchi, Y (reprint author), Natl Ctr Neurol & Psychiat, Dept Psychophysiol, Natl Inst Mental Hlth, 4-1-1 Ogawahigashi, Kodaira, Tokyo 1870031, Japan. EM ymorigu@ncnp.go.jp FU National Institutes of Health [DP10D003312]; National Institute on Aging [R01 AG030311]; [R01-AG029480]; [NCRR P41-RR14075]; [1S10RR023401]; [1S10RR019307]; [1S10RR023043] FX This work was supported in part by the National Institutes of Health Director's Pioneer Award (DP10D003312) and a National Institute on Aging grant (R01 AG030311) to L. F. B, as well as the following grants: R01-AG029480 to B. C. D. and shared resource/instrumentation grants NCRR P41-RR14075, 1S10RR023401, 1S10RR019307 and 1S10RR023043. NR 94 TC 15 Z9 15 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD MAY PY 2014 VL 9 IS 5 BP 591 EP 600 DI 10.1093/scan/nst030 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AH9UK UT WOS:000336489000004 PM 23596188 ER PT J AU Hankey, GJ Stevens, SR Piccini, JP Lokhnygina, Y Mahaffey, KW Halperin, JL Patel, MR Breithardt, G Singer, DE Becker, RC Berkowitz, SD Paolini, JF Nessel, CC Hacke, W Fox, KAA Califf, RM AF Hankey, Graeme J. Stevens, Susanna R. Piccini, Jonathan P. Lokhnygina, Yuliya Mahaffey, Kenneth W. Halperin, Jonathan L. Patel, Manesh R. Breithardt, Guenter Singer, Daniel E. Becker, Richard C. Berkowitz, Scott D. Paolini, John F. Nessel, Christopher C. Hacke, Werner Fox, Keith A. A. Califf, Robert M. CA ROCKET AF Steering Comm Investigat TI Intracranial Hemorrhage Among Patients With Atrial Fibrillation Anticoagulated With Warfarin or Rivaroxaban The Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation SO STROKE LA English DT Article DE anticoagulation; atrial fibrillation; intracranial hemorrhage; risk prediction ID CHRONIC KIDNEY-DISEASE; NET CLINICAL BENEFIT; RISK-FACTORS; INTRACEREBRAL HEMORRHAGE; BLEEDING RISK; ELDERLY-PATIENTS; ISCHEMIC-STROKE; POPULATION; VALIDATION; MANAGEMENT AB Background and Purpose Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. Methods We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used. Results During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210x10(9)/L (1.08; 1.02-1.13 per 10x10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Conclusions Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations. C1 [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Hankey, Graeme J.] Sir Charles Gairdner Hosp, Dept Neurol, Perth, WA, Australia. [Stevens, Susanna R.; Piccini, Jonathan P.; Lokhnygina, Yuliya; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. [Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Breithardt, Guenter] Hosp Univ Munster, Dept Cardiovasc Med, Munster, Germany. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Dept Global Clin Dev, Whippany, NJ USA. [Paolini, John F.] Cerenis Therapeut, Labege, France. [Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Hankey, GJ (reprint author), Univ Western Australia, Sch Med & Pharmacol, QEII Med Ctr, Harry Perkins Inst Med Res, Room 222,QQ Block,6 Verdun St, Perth, WA 6009, Australia. EM graeme.hankey@uwa.edu.au 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) FX The trial was supported by research grants from Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ) and Bayer HealthCare AG (Leverkusen, Germany). NR 43 TC 36 Z9 37 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2014 VL 45 IS 5 BP 1304 EP 1312 DI 10.1161/STROKEAHA.113.004506 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AG7DK UT WOS:000335578100031 PM 24743444 ER PT J AU Xian, Y Smith, EE Zhao, X Peterson, ED Olson, DM Hernandez, AF Bhatt, DL Saver, JL Schwamm, LH Fonarow, GC AF Xian, Ying Smith, Eric E. Zhao, Xin Peterson, Eric D. Olson, DaiWai M. Hernandez, Adrian F. Bhatt, Deepak L. Saver, Jeffrey L. Schwamm, Lee H. Fonarow, Gregg C. TI Strategies Used by Hospitals to Improve Speed of Tissue-Type Plasminogen Activator Treatment in Acute Ischemic Stroke SO STROKE LA English DT Article DE quality of health care; quality improvement; stroke ID ELEVATION MYOCARDIAL-INFARCTION; DOOR-TO-BALLOON; GUIDELINES-STROKE; INTRAVENOUS THROMBOLYSIS; EARLY MANAGEMENT; NEEDLE TIMES; CARE; ASSOCIATION; QUALITY; DELAYS AB Background and Purpose The benefits of intravenous tissue-type plasminogen activator in acute ischemic stroke are time dependent, and several strategies have been reported to be associated with more rapid door-to-needle (DTN) times. However, the extent to which hospitals are using these strategies and their association with DTN times have not been well studied. Methods We surveyed 304 Get With The Guidelines-Stroke hospitals joining Target: Stroke regarding their baseline use of strategies to reduce DTN times in the January 2008 to December 2009 time frame before the initiation of Target: Stroke and determined the association between hospital strategies and DTN times. Results Among 5460 patients receiving tissue-type plasminogen activator within 3 hours of symptom onset in surveyed hospitals, the median DTN time was 72 minutes (interquartile range, 55-94). Reported use of the different strategies varied considerably. Of 11 hospital strategies analyzed individually by multivariable analysis, 3 strategies were independently associated with shorter DTN times. These included rapid triage/stroke team notification (209/304 [69%] hospitals, 8.1-minute reduction in DTN time), single-call activation system (190/304 [63%] hospitals, 4.3 minutes), and tissue-type plasminogen activator stored in the emergency department (189/304 [62%] hospitals, 3.5 minutes). When analyzed incrementally, hospitals that used a greater number of strategies had shorter DTN times with 1.3 minutes (adjusted mean difference) saved for each strategy implemented (14 minutes if all strategies were used). Conclusions Although the majority of participating hospitals reported using some strategy to reduce delays in tissue-type plasminogen activator administration for acute ischemic stroke, the strategies applied vary considerably and those most strongly associated with shorter DTN times were applied relatively less frequently. C1 [Xian, Ying; Zhao, Xin; Peterson, Eric D.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Olson, DaiWai M.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu RI Hernandez, Adrian F./A-7818-2016; OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU American Heart Association/American Stroke Association FX Target: Stroke is an initiative provided by the American Heart Association/American Stroke Association. NR 36 TC 25 Z9 25 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2014 VL 45 IS 5 BP 1387 EP 1395 DI 10.1161/STROKEAHA.113.003898 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AG7DK UT WOS:000335578100044 PM 24713527 ER PT J AU Abou-Chebl, A Zaidat, OO Castonguay, AC Gupta, R Sun, CHJ Martin, CO Holloway, WE Mueller-Kronast, N English, JD Linfante, I Dabus, G Malisch, TW Marden, FA Bozorgchami, H Xavier, A Rai, AT Froehler, MT Badruddin, A Nguyen, TN Taqi, M Abraham, MG Janardhan, V Shaltoni, H Novakovic, R Yoo, AJ Chen, PR Britz, GW Kaushal, R Nanda, A Issa, MA Nogueira, RG AF Abou-Chebl, Alex Zaidat, Ossama O. Castonguay, Alicia C. Gupta, Rishi Sun, Chung-Huan J. Martin, Coleman O. Holloway, William E. Mueller-Kronast, Nils English, Joey D. Linfante, Italo Dabus, Guilherme Malisch, Timothy W. Marden, Franklin A. Bozorgchami, Hormozd Xavier, Andrew Rai, Ansaar T. Froehler, Micahel T. Badruddin, Aamir Nguyen, Thanh N. Taqi, Muhammad Abraham, Michael G. Janardhan, Vallabh Shaltoni, Hashem Novakovic, Roberta Yoo, Albert J. Chen, Peng R. Britz, Gavin W. Kaushal, Ritesh Nanda, Ashish Issa, Mohammad A. Nogueira, Raul G. TI North American SOLITAIRE Stent-Retriever Acute Stroke Registry Choice of Anesthesia and Outcomes SO STROKE LA English DT Article DE anesthesia; stroke ID ACUTE ISCHEMIC-STROKE; BLOOD-PRESSURE; ENDOVASCULAR THERAPY; GENERAL-ANESTHESIA; CLINICAL-OUTCOMES; POOLED ANALYSIS; TRIAL; THROMBOLYSIS; REVASCULARIZATION; THROMBECTOMY AB Background and Purpose Previous work that predated the availability of the safer stent-retriever devices has suggested that general anesthesia (GA) may have a negative impact on outcomes in patients with acute ischemic stroke undergoing endovascular therapy. Methods We reviewed demographic, clinical, procedural (GA versus local anesthesia [LA], etc), and site-adjudicated angiographic and clinical outcomes data from consecutive patients treated with the Solitaire FR device in the investigator-initiated North American SOLITAIRE Stent-Retriever Acute Stroke (NASA) Registry. The primary outcomes were 90-day modified Rankin Scale, mortality, and symptomatic intracranial hemorrhage. Results A total of 281 patients from 18 centers were enrolled. GA was used in 69.8% (196/281) of patients. Baseline demographic and procedural factors were comparable between the LA and GA groups, except the former demonstrated longer time-to-groin puncture (395.4254 versus 337.4 +/- 208 min; P=0.04), lower National Institutes of Health Stroke Scale (NIHSS; 16.2 +/- 5.8 versus 18.8 +/- 6.9; P=0.002), lower balloon-guide catheter usage (22.4% versus 49.2%; P=0.0001), and longer fluoroscopy times (39.5 +/- 33 versus 28 +/- 22.8 min; P=0.008). Recanalization (thrombolysis in cerebral infarction 2b; 72.94% versus 73.6%; P=0.9) and rate of symptomatic intracranial hemorrhage (7.1% versus 11.2%; P=0.4) were similar but modified Rankin Scale 2 was achieved in more LA patients, 52.6% versus 35.6% (odds ratio, 1.4 [1.1-1.8]; P=0.01). In multivariate analysis, hypertension, NIHSS, unsuccessful revascularization, and GA use (odds ratio, 3.3 [1.6-7.1]; P=0.001) were associated with death. When only anterior circulation and elective GA patients were included, there was a persistent difference in good outcomes in favor of LA patients (50.7% versus 35.5%; odds ratio, 1.3 [1.01-1.6]; P=0.04). Conclusions The NASA Registry has demonstrated that clinical outcomes and survival are significantly better in patients treated with LA, without increased symptomatic intracranial hemorrhage risk. Future trials should prospectively evaluate the effect of GA on outcomes. C1 [Abou-Chebl, Alex; Janardhan, Vallabh] Texas Stroke Inst, Plano, TX 75075 USA. [Zaidat, Ossama O.; Castonguay, Alicia C.; Issa, Mohammad A.] Med Coll Wisconsin, Froedtert Hosp, Dept Neurol, Atlanta, GA USA. [Zaidat, Ossama O.; Castonguay, Alicia C.; Issa, Mohammad A.] Med Coll Wisconsin, Froedtert Hosp, Dept Neurosurg, Atlanta, GA USA. [Zaidat, Ossama O.; Castonguay, Alicia C.; Issa, Mohammad A.] Med Coll Wisconsin, Froedtert Hosp, Dept Radiol, Atlanta, GA USA. [Gupta, Rishi] Wellstar Neurosurg Kennestone Hosp, Atlanta, GA USA. [Sun, Chung-Huan J.; Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Martin, Coleman O.; Holloway, William E.] St Lukes Kansas City, Kansas City, MO USA. [Mueller-Kronast, Nils] Delray Med Ctr, Dept Neurol, Delray Beach, FL USA. [English, Joey D.] Calif Pacif Med Ctr, San Francisco, CA USA. [Linfante, Italo; Dabus, Guilherme] Baptist Cardiac & Vasc Inst, Div Intervent Neuroradiol, Miami, FL USA. [Malisch, Timothy W.; Marden, Franklin A.] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Bozorgchami, Hormozd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Xavier, Andrew] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Rai, Ansaar T.] West Virginia Univ Hosp, Dept Radiol, Morgantown, WV USA. [Froehler, Micahel T.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN USA. [Badruddin, Aamir] Provena St Joseph Med Ctr, Joliet, IL USA. [Nguyen, Thanh N.] Boston Med Ctr, Dept Neurol, Boston, MA USA. [Taqi, Muhammad] Desert Reg Med Ctr, Palm Springs, CA USA. [Abraham, Michael G.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Shaltoni, Hashem] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Novakovic, Roberta] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. [Chen, Peng R.] Univ Texas Houston, Houston, TX USA. [Britz, Gavin W.] Houston Methodist, Methodist Neurol Inst, Dept Neurosurg, Houston, TX USA. [Kaushal, Ritesh] St Louis Univ, St Louis, MO 63103 USA. [Nanda, Ashish] Univ Missouri, Columbia, MO USA. RP Abou-Chebl, A (reprint author), Texas Stroke Inst, 1600 Coit Rd, Plano, TX 75075 USA. EM achebl@yahoo.com RI Demchuk, Andrew/E-1103-2012 OI Demchuk, Andrew/0000-0002-4930-7789 NR 26 TC 29 Z9 29 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2014 VL 45 IS 5 BP 1396 EP 1401 DI 10.1161/STROKEAHA.113.003698 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AG7DK UT WOS:000335578100045 PM 24668201 ER PT J AU Blasi, F Wei, Y Balkaya, M Tikka, S Mandeville, JB Waeber, C Ayata, C Moskowitz, MA AF Blasi, Francesco Wei, Ying Balkaya, Mustafa Tikka, Saara Mandeville, Joseph B. Waeber, Christian Ayata, Cenk Moskowitz, Michael A. TI Recognition Memory Impairments After Subcortical White Matter Stroke in Mice SO STROKE LA English DT Article DE mild cognitive impairment; models; animal; stroke; lacunar; white matter diseases ID CHRONIC CEREBRAL HYPOPERFUSION; CAROTID-ARTERY OCCLUSION; SMALL VESSEL DISEASE; COGNITIVE IMPAIRMENT; EPISODIC MEMORY; L-ARGININE; IN-VIVO; LESIONS; MODEL; ENDOTHELIN-1 AB Background and Purpose Small subcortical white matter infarcts are a common stroke subtype often associated with cognitive deficits. The lack of relevant models confined to white matter has limited the investigation of its pathophysiology. Here, we examine tissue and functional outcome after an ischemic lesion within corpus callosum in wild-type (WT) mice and in mice null for a gene, NOTCH3, linked to white matter ischemic injury in patients. Methods WT and NOTCH3 knockout mice were subjected to stereotactic microinjections of the potent vasoconstrictor endothelin-1 at the level of periventricular white matter to induce a focal ischemic lesion. Infarct location was confirmed by MRI, and brains were examined for lesion size and histology; behavioral deficits were assessed 1 month in WT mice. Results Ischemic damage featured an early cerebral blood flow deficit, blood-brain barrier opening, and a lesion largely confined to white matter. At later stages, myelin and axonal degeneration and microglial/macrophage infiltration were found. WT mice displayed prolonged cognitive deficit when tested using a novel object recognition task. NOTCH3 mutants showed larger infarcts and greater cognitive deficit at 7 days post stroke. Conclusions Taken together, these data show the usefulness of microinjections of endothelin-1 into periventricular white matter to study focal infarcts and cognitive deficit in WT mice. In short-term studies, stroke outcome was worse in NOTCH3 null mice, consistent with the notion that the lack of the NOTCH3 receptor affects white matter stroke susceptibility. C1 [Blasi, Francesco; Wei, Ying; Balkaya, Mustafa; Ayata, Cenk; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Res Lab,Dept Radiol, Boston, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit,Dept Neurol, Boston, MA USA. [Tikka, Saara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cell Biol, Boston, MA USA. [Mandeville, Joseph B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Martinos Ctr Biomed Imaging, Boston, MA USA. [Waeber, Christian] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Dept Pharmacol, Cork, Ireland. RP Blasi, F (reprint author), Massachusetts Gen Hosp, Dept Radiol, Bldg 149,13th St,Room 6401, Charlestown, MA 02129 USA. EM Blasi.Francesco@mgh.harvard.edu RI Blasi, Francesco/G-1055-2015; Waeber, Christian/A-8333-2009 OI Blasi, Francesco/0000-0002-6616-8418; Waeber, Christian/0000-0001-6078-0027 FU National Institutes of Health; Fondation Leducq; Neuroendovascular Research Fund from the Andrew David Heitman Foundation; Ellison Foundation FX This work was supported by grants from National Institutes of Health (Dr Moskowitz), Fondation Leducq, Neuroendovascular Research Fund from the Andrew David Heitman Foundation, and The Ellison Foundation (Dr Ayata). NR 28 TC 11 Z9 11 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2014 VL 45 IS 5 BP 1468 EP 1473 DI 10.1161/STROKEAHA.114.005324 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AG7DK UT WOS:000335578100056 PM 24723319 ER PT J AU Davis, MM Freeman, M Kaye, J Vuckovic, N Buckley, DI AF Davis, Melinda M. Freeman, Michele Kaye, Jeffrey Vuckovic, Nancy Buckley, David I. TI A Systematic Review of Clinician and Staff Views on the Acceptability of Incorporating Remote Monitoring Technology into Primary Care SO TELEMEDICINE AND E-HEALTH LA English DT Article DE home health monitoring; e-health; telehealth ID NORTHERN GERMANY; CHRONIC DISEASE; TELEHOMECARE; PILOT; PROGRAM; DEVICES; DESIGN; ISSUES; HEALTH; HOME AB Objective:Remote monitoring technology (RMT) may enhance healthcare quality and reduce costs. RMT adoption depends on perceptions of the end-user (e.g., patients, caregivers, healthcare providers). We conducted a systematic review exploring the acceptability and feasibility of RMT use in routine adult patient care, from the perspectives of primary care clinicians, administrators, and clinic staff.Materials and Methods:We searched the databases of Medline, IEEE Xplore, and Compendex for original articles published from January 1996 through February 2013. We manually screened bibliographies of pertinent studies and consulted experts to identify English-language studies meeting our inclusion criteria.Results:Of 939 citations identified, 15 studies reported in 16 publications met inclusion criteria. Studies were heterogeneous by country, type of RMT used, patient and provider characteristics, and method of implementation and evaluation. Clinicians, staff, and administrators generally held positive views about RMTs. Concerns emerged regarding clinical relevance of RMT data, changing clinical roles and patterns of care (e.g., reduced quality of care from fewer patient visits, overtreatment), insufficient staffing or time to monitor and discuss RMT data, data incompatibility with a clinic's electronic health record (EHR), and unclear legal liability regarding response protocols.Conclusions:This small body of heterogeneous literature suggests that for RMTs to be adopted in primary care, researchers and developers must ensure clinical relevance, support adequate infrastructure, streamline data transmission into EHR systems, attend to changing care patterns and professional roles, and clarify response protocols. There is a critical need to engage end-users in the development and implementation of RMT. C1 [Davis, Melinda M.; Buckley, David I.] Oregon Hlth & Sci Univ, Oregon Rural Practice Based Res Network, Portland, OR 97239 USA. [Davis, Melinda M.; Buckley, David I.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Buckley, David I.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Buckley, David I.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97239 USA. [Freeman, Michele] Portland VA Med Ctr, VA Evidence Based Synth Program, Portland, OR USA. [Kaye, Jeffrey] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. [Vuckovic, Nancy] Intel Corp, Hillsboro, OR 97124 USA. RP Davis, MM (reprint author), Oregon Hlth & Sci Univ, Dept Family Med, 3181 SW Sam Jackson Pk Rd,Mail Code L222, Portland, OR 97239 USA. EM davismel@ohsu.edu; freemanm@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU Oregon Roybal Center for Translational Research on Aging at OHSU, Portland, OR [P30AG024978]; Clinical and Translational Science Award from the National Center for Research Resources, National Institutes of Health [1 UL1 RR024140 01]; National Institute on Aging, National Institutes of Health [P30AG024978, P30AG008017] FX We thank Andrew Hamilton, Oregon Health & Science University (OHSU) senior reference and instruction librarian, for his assistance with the search strategy. Funding for this project is provided by the Oregon Roybal Center for Translational Research on Aging (grant P30AG024978) at OHSU, Portland, OR, and by a Clinical and Translational Science Award to OHSU (grant 1 UL1 RR024140 01 from the National Center for Research Resources, National Institutes of Health). J.K.'s time was supported by grants P30AG024978 and P30AG008017 from the National Institute on Aging, National Institutes of Health. NR 28 TC 6 Z9 6 U1 0 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD MAY 1 PY 2014 VL 20 IS 5 BP 428 EP 438 DI 10.1089/tmj.2013.0166 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AG4MG UT WOS:000335393400006 PM 24731239 ER PT J AU Vagefi, PA Patel, MS LaMuraglia, GM AF Vagefi, Parsia A. Patel, Madhukar S. LaMuraglia, Glenn M. TI Endovascular Stent for Iatrogenic Penetrating Injury of the Thoracic Aorta SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE aortic injury; thoracic aortic stent graft; endovascular therapy ID SINGLE-CENTER EXPERIENCE; GRAFTS; REPAIR; ANEURYSMS; RUPTURE AB Purpose: This is a report of the endovascular management of an iatrogenic descending thoracic aortic injury with long-term follow-up. Case Report: A 74-year-old medically complex female underwent the inadvertent percutaneous placement of a 6F sheath directly into the descending thoracic aorta during an attempted pericardiocentesis at an outside hospital. Upon transfer, the patient underwent endovascular placement of a thoracic stent graft to cover the entry site and recovered without incidence. The patient has remained free of complications for nearly 8 years of follow-up care. Conclusions: Endovascular stent graft utilization of the thoracic aorta has increased the treatment scope for the management of emergent and elective aortic pathology. This is particularly useful in clinical scenarios deemed too high an open surgical risk secondary to significant comorbidities. C1 [Vagefi, Parsia A.; Patel, Madhukar S.; LaMuraglia, Glenn M.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,White 544b, Boston, MA 02114 USA. EM pvagefi@partners.org NR 15 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 EI 1938-9116 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD MAY PY 2014 VL 48 IS 4 BP 333 EP 336 DI 10.1177/1538574413518617 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AH2HD UT WOS:000335941200005 PM 24407508 ER PT J AU Gifford, KA Liu, DD Lu, ZQ Tripodis, Y Cantwell, NG Palmisano, J Kowall, N Jefferson, AL AF Gifford, Katherine A. Liu, Dandan Lu, Zengqi Tripodis, Yorghos Cantwell, Nicole G. Palmisano, Joseph Kowall, Neil Jefferson, Angela L. TI The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults SO ALZHEIMERS & DEMENTIA LA English DT Article DE Mild cognitive impairment; Alzheimer's disease; Cognitive complaints; Prognosis; Conversion ID SUBJECTIVE MEMORY COMPLAINTS; UNIFORM DATA SET; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; INTERNATIONAL WORKSHOP; PATHOLOGICAL DIAGNOSIS; PHYSICAL-ACTIVITY; TASK-FORCE; IMPAIRMENT; DEMENTIA AB Objective: The objective of this study was to compare whether different sources of cognitive complaint (i.e., subjective and informant) predict diagnostic conversion in nondemented older adults. Methods: Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 4414; mean age, 73 +/- 8 years; 69% female) or mild cognitive impairment (MCI; n = 1843; mean age, 74 +/- 8 years; 52% female). Multinomial logistic regression related baseline cognitive complaint (no complaint, self only, informant only, or both self and informant) to diagnostic outcome (reversion, stable, or conversion). Results: At follow-up, 14% of NC participants converted to MCI/dementia (3.5 +/- 1.8 years), and 41% of MCI participants converted to dementia (3.0 +/- 1.6 years). Among NC participants, self complaint only (odds ratio [OR], 2.1; 99% confidence interval (CI),1.5-2.9; P < .001), informant complaint only (OR, 2.2; 99% CI, 1.2-3.9; P < .001), and both self and informant complaint (OR, 4.2; 99% CI, 2.9-6.0; P < .001) were associated with diagnostic conversion compared with no complaint. Among participants with MCI-compared with no complaint, informant complaint only (OR, 2.2; 99% CI, 1.2-4.3, P = .002), and both self and informant complaint (OR, 2.9; 99% CI, 1.8-4.8; P < .001) were associated with conversion. Conclusions: Cognitive complaints are related to conversion among nondemented older adults. Complaint from both (i.e. mutual complaint) sources was most predictive of diagnostic outcome, followed by informant complaint, highlighting the need for obtaining informant corroboration to enhance prognosis and distinguish underlying pathological processes from normal cognitive aging. Self complaint was related inconsistently to diagnostic outcome. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Gifford, Katherine A.; Jefferson, Angela L.] Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN 37235 USA. [Liu, Dandan; Lu, Zengqi] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Tripodis, Yorghos; Cantwell, Nicole G.; Palmisano, Joseph; Kowall, Neil] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Tripodis, Yorghos] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Palmisano, Joseph] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Kowall, Neil] VA Boston Healthcare Syst, Boston, MA USA. RP Jefferson, AL (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN 37235 USA. EM angela.jefferson@vanderbilt.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Tripodis, Yorghos/0000-0003-2190-7608 FU NACC Junior Investigator [2011-JI-08]; Alzheimer's Association [IIRG-08-88733, R01-AG034962, R01-HL11516]; Vanderbilt Memory & Alzheimer's Center; [T32-AG036697]; [K23-AG030962]; [P30-AG013846]; [M01-RR00533]; [U01-A0016976] FX This research was supported by NACC Junior Investigator Award no. 2011-JI-08 (K.A.G.); T32-AG036697 (K.A.G), K23-AG030962 (Paul, B. Beeson Career Development Award in Aging [A.L.J.]), Alzheimer's Association IIRG-08-88733 (A.L.J.), R01-AG034962 (A.L.J.), R01-HL11516 (A.L.J.), P30-AG013846 (Boston University Alzheimer's Disease Core Center), M01-RR00533 (General Clinical Research Centers Program of the National Center for Research Resources, National Institutes of Health), U01-A0016976 (NACC), and the Vanderbilt Memory & Alzheimer's Center, (K.A.G., A.L.J.). NR 51 TC 24 Z9 24 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2014 VL 10 IS 3 BP 319 EP 327 DI 10.1016/j.jalz.2013.02.007 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AG7WG UT WOS:000335628900006 PM 23871264 ER PT J AU Gandaglia, G Karakiewicz, PI Briganti, A Trinh, QD Schiffmann, J Tian, Z Kim, SP Nguyen, PL Graefen, M Montorsi, F Sun, M Abdollah, F AF Gandaglia, G. Karakiewicz, P. I. Briganti, A. Trinh, Q. D. Schiffmann, J. Tian, Z. Kim, S. P. Nguyen, P. L. Graefen, M. Montorsi, F. Sun, M. Abdollah, F. TI Intensity-modulated radiation therapy leads to survival benefit only in patients with high-risk prostate cancer: a population-based study SO ANNALS OF ONCOLOGY LA English DT Article DE prostate cancer; intensity-modulated radiation therapy; survival; cancer-specific mortality; competing risks ID PROPENSITY SCORE METHODS; RADICAL PROSTATECTOMY; INITIAL TREATMENT; MEN; TECHNOLOGIES; TOXICITY AB During the last years, there has been a rapid adoption of intensity-modulated radiation therapy (IMRT) in patients with prostate cancer (PCa), despite the lack of randomized trials evaluating its effectiveness. The aim of our study was to evaluate the survival benefit associated with IMRT in patients with PCa. Overall, 42 483 patients with PCa treated with IMRT or initial observation between 2001 and 2007 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare were evaluated. Patients in both treatment arms were matched using propensity-score methodology. After propensity-score matching, 19 064 patients remained in our analyses. Eight-year cancer-specific mortality (CSM) rates were estimated, and the number needed to treat (NNT) was calculated. Competing risks regression analyses tested the relationship between treatment type and CSM. Overall, the 8-year CSM rates were 3.4% and 4.1% for patients treated with IMRT versus initial observation, respectively (P < 0.001). The corresponding 8-year NNT was 142. In patients with low/intermediate-risk disease, IMRT was not associated with lower CSM rates compared with observation (P = 0.7). In patients with high-risk disease, the 8-year CSM rates for IMRT versus observation were 5.8% versus 10.5%, respectively (P < 0.001). The corresponding NNT was 21. When high-risk patients were stratified according to age (< 73 versus a parts per thousand yen73), and Charlson comorbidity index (a parts per thousand currency sign1 versus > 1) the 8-year CSM rates for IMRT versus observation were 4.3% versus 9.4% and 6.9% versus 11.9% and 5.3% versus 11.4% and 6.1% versus 10.1%, respectively (all Ps < 0.001). The corresponding NNTs were 19, 21, 16, and 25, respectively. In multivariate analyses, the protective effect of IMRT was more evident in high-risk patients with younger age and lower comorbidities. IMRT leads to a survival advantage only in patients with high-risk disease. Conversely, patients with low/intermediate-risk disease did not benefit from IMRT at 8-year follow-up. C1 [Gandaglia, G.; Karakiewicz, P. I.; Briganti, A.; Schiffmann, J.; Tian, Z.; Sun, M.; Abdollah, F.] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Gandaglia, G.; Montorsi, F.; Abdollah, F.] Univ Vita Salute San Raffaele, Urol Res Inst, San Raffaele Sci Inst, Dept Urol, Milan, Italy. [Karakiewicz, P. I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ, Canada. [Trinh, Q. D.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA. [Kim, S. P.] Yale Univ, Dept Urol, New Haven, CT USA. [Nguyen, P. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Graefen, M.] Univ Med Ctr Hamburg Eppendorf, Martiniclin, Hamburg, Germany. [Abdollah, F.] Vattikuti Urol Inst, Detroit, MI USA. [Abdollah, F.] VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. RP Abdollah, F (reprint author), Henry Ford Hosp, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM firas.abdollah@gmail.com OI , Jonas/0000-0002-0654-5920 NR 20 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2014 VL 25 IS 5 BP 979 EP 986 DI 10.1093/annonc/mdu087 PG 8 WC Oncology SC Oncology GA AG9XV UT WOS:000335774200010 PM 24562445 ER PT J AU Lippa, SM Pastorek, NJ Romesser, J Linck, J Sim, AH Wisdom, NM Miller, BI AF Lippa, Sara M. Pastorek, Nicholas J. Romesser, Jennifer Linck, John Sim, Anita H. Wisdom, Nick M. Miller, Brian I. TI Ecological Validity of Performance Validity Testing SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Performance validity test; Mild traumatic brain injury; Response bias; Veterans; Mayo-Portland Adaptability Inventory Participation Index ID TRAUMATIC BRAIN-INJURY; MALINGERED NEUROCOGNITIVE DYSFUNCTION; FAKE-BAD SCALE; SYMPTOM VALIDITY; NEUROPSYCHOLOGICAL ASSESSMENT; HEAD-INJURY; MMPI-2; COMPENSATION; EXAGGERATION; INCENTIVES AB Performance validity tests (PVTs) have been shown to relate to neuropsychological performance, but no studies have looked at the ecological validity of these measures. Data from 131 veterans with a history of mild traumatic brain injury from a multicenter Veterans Administration consortium were examined to determine the relation between scores on a self-report version of the Mayo-Portland Adaptability Inventory Participation Index, a measure of community participation, and the Word Memory Test, a PVT. A restricted regression model, including education, age, history of loss of consciousness, cognitive measures, and a measure of symptom validity test performance, was not significantly associated with self-reported community reintegration. Adding PVT results to the restricted model, however, did significantly improve the prediction of community reintegration as PVT failure was associated with lower self-reported community participation. The results of this study indicate that PVTs may also serve as an indicator of patients' functioning in the community. C1 [Lippa, Sara M.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders, Boston, MA 02130 USA. [Pastorek, Nicholas J.; Wisdom, Nick M.; Miller, Brian I.] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Pastorek, Nicholas J.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Romesser, Jennifer] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. [Linck, John] Oklahoma City VA Med Ctr, Oklahoma City, OK 73104 USA. [Sim, Anita H.] Minneapolis VA Hlth Care Syst, Minneapolis, MN 55417 USA. [Wisdom, Nick M.; Miller, Brian I.] Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. RP Pastorek, NJ (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd RECL 117, Houston, TX 77030 USA. EM nicholas.pastorek@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA RR&D Traumatic Brain Injury Center of Excellence, Neurorehabilitation: Neurons to Networks [B6812C]; Minnesota Veterans Medical Research & Education Foundation FX No pharmaceutical or corporate funding was used in the preparation of this manuscript or collection of data. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; B6812C (PI-Levin HS) VA RR&D Traumatic Brain Injury Center of Excellence, Neurorehabilitation: Neurons to Networks, as well as the Minnesota Veterans Medical Research & Education Foundation. NR 48 TC 8 Z9 8 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAY PY 2014 VL 29 IS 3 BP 236 EP 244 DI 10.1093/arclin/acu002 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA AG9WC UT WOS:000335769700003 PM 24681945 ER PT J AU Fazeli, PL Doyle, KL Scott, JC Iudicello, JE Casaletto, KB Weber, E Moore, DJ Morgan, EE Grant, I Woods, SP AF Fazeli, Pariya L. Doyle, Katie L. Scott, J. Cobb Iudicello, Jennifer E. Casaletto, Kaitlin B. Weber, Erica Moore, David J. Morgan, Erin E. Grant, Igor Woods, Steven Paul CA HIV Neurobehav Res Program HNRP TI Shallow Encoding and Forgetting Are Associated with Dependence in Instrumental Activities of Daily Living Among Older Adults Living with HIV Infection SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Aging; Disability; Everyday functioning; Learning and memory ID HUMAN-IMMUNODEFICIENCY-VIRUS; VERBAL MEMORY PERFORMANCE; NEUROCOGNITIVE DISORDERS; NEUROPSYCHOLOGICAL PERFORMANCE; COGNITIVE IMPAIRMENT; MEDICATION ADHERENCE; CORTICAL HYPOTHESIS; CONSTRUCT-VALIDITY; YOUNGER ADULTS; LEARNING TEST AB Aging and HIV are both risk factors for memory deficits and declines in real-world functioning. However, we know little about the profile of memory deficits driving instrumental activities of daily living (IADL) declines across the lifespan in HIV. This study examined 145 younger (< 50 years) and 119 older (a parts per thousand yen50 years) adults with HIV who completed the California Verbal Learning Test-Second Edition (CVLT-II), the Wechsler Memory Scale-Third Edition Logical Memory subtest (WMS-III LM), and a modified Lawton and Brody ADL questionnaire. No memory predictors of IADL dependence emerged in the younger cohort. In the older group, IADL dependence was uniquely associated with worse performance on all primary CVLT-II variables, as well as elevated recency effects. Poorer immediate and delayed recall of the WMS-III LM was also associated with IADL dependence, although recognition was intact. Findings suggest older HIV-infected adults with shallow encoding and forgetting are at risk for IADL dependence. C1 [Fazeli, Pariya L.; Doyle, Katie L.; Iudicello, Jennifer E.; Casaletto, Kaitlin B.; Weber, Erica; Moore, David J.; Morgan, Erin E.; Grant, Igor; Woods, Steven Paul] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Doyle, Katie L.; Casaletto, Kaitlin B.; Weber, Erica] San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. [Doyle, Katie L.; Casaletto, Kaitlin B.; Weber, Erica] Univ Calif San Diego, San Diego, CA 92103 USA. [Scott, J. Cobb] Univ Penn, Dept Psychiat, Perelman Sch Med, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Scott, J. Cobb] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Scott, J. Cobb] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA. RP Woods, SP (reprint author), Univ Calif San Diego, Dept Psychiat 8231, 220 Dickinson St,Suite B, San Diego, CA 92103 USA. EM spwoods@ucsd.edu FU National Institutes of Health (NIH) [R01-MH073419, T32-DA031098, P30-MH062512, F31-DA034510, F31-DA035708, L30-DA032120, L30-DA034362]; California HIV/AIDS Research Program (CHRP) [R25-MH081482, R01-MH099987, L30-AG045921, ID10-SD-057] FX This research was supported by National Institutes of Health (NIH) grants R01-MH073419, T32-DA031098, P30-MH062512, F31-DA034510, F31-DA035708, L30-DA032120, and L30-DA034362. Dr. Fazeli is supported by R25-MH081482, R01-MH099987, L30-AG045921, and ID10-SD-057 from California HIV/AIDS Research Program (CHRP). NR 64 TC 2 Z9 2 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAY PY 2014 VL 29 IS 3 BP 278 EP 288 DI 10.1093/arclin/acu009 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA AG9WC UT WOS:000335769700007 PM 24695591 ER PT J AU Blashill, AJ Mayer, KH Crane, HM Baker, JS Willig, JH Willig, AL Grasso, C O'Cleirigh, C Safren, SA AF Blashill, Aaron J. Mayer, Kenneth H. Crane, Heidi M. Baker, Joshua S. Willig, James H. Willig, Amanda L. Grasso, Chris O'Cleirigh, Conall Safren, Steven A. TI Body Mass Index, Depression, and Condom Use Among HIV-Infected Men who have Sex with Men: A Longitudinal Moderation Analysis SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE HIV/AIDS; Depression; Obesity; Sexual risk; Body mass index; Condom use ID RISK BEHAVIORS; ANTIRETROVIRAL THERAPY; PRIMARY-CARE; OBESITY; COHORT; IMAGE; SATISFACTION; COINFECTION; PROGRESSION; OVERWEIGHT AB Findings have been inconsistent regarding the association of obesity and sexual risk behaviors. The purpose of the current study was to assess the prospective nature of body mass index (BMI), depression, and their interaction in predicting condom use during anal intercourse among HIV-infected men who have sex with men (MSM). The sample (N = 490) was obtained from a large, HIV clinical cohort from four sites across the U.S. The following inclusion criteria were employed: identification as MSM and had completed at least one wave of patient-reported measures (e.g., depression, as measured by the PHQ-9) in the clinical cohort study. Longitudinal linear mixed-effects modeling revealed a significant BMI by depression interaction. Depressive symptoms were predictive of less frequent condom use for obese but not overweight men. Analogous results were found in regard to comparisons between normal weight and overweight men. Obesity, in the context of depression, is a risk factor for unprotected anal intercourse among HIV-infected MSM. Cognitive behavioral interventions to reduce HIV transmission risk behaviors among HIV-infected MSM should adopt an integrated perspective, combining sexual risk reduction with treatment for depression and body-related concerns. C1 [Blashill, Aaron J.; O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.; Baker, Joshua S.; Grasso, Chris; O'Cleirigh, Conall; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Blashill, Aaron J.; Baker, Joshua S.; Grasso, Chris; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Crane, Heidi M.] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. [Willig, James H.; Willig, Amanda L.] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org OI Willig, Amanda/0000-0001-8802-4311 FU NIAAA NIH HHS [U01 AA020793]; NIAID NIH HHS [P30 AI060354, P30 AI027757, R24 AI067039, R24AI067039]; NIAMS NIH HHS [U01 AR057954, U01AR057954]; NIMH NIH HHS [K24MH094214, K24 MH094214, R01 MH084759, K23MH096647, K23 MH096647] NR 33 TC 3 Z9 3 U1 5 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 EI 1573-2800 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD MAY PY 2014 VL 43 IS 4 BP 729 EP 734 DI 10.1007/s10508-013-0155-4 PG 6 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA AG9UL UT WOS:000335765300008 PM 23979782 ER PT J AU Shum, WW Smith, TB Cortez-Retamozo, V Grigoryeva, LS Roy, JW Hill, E Pittet, MJ Breton, S Da Silva, N AF Shum, Winnie W. Smith, Tegan B. Cortez-Retamozo, Virna Grigoryeva, Lubov S. Roy, Jeremy W. Hill, Eric Pittet, Mikael J. Breton, Sylvie Da Silva, Nicolas TI Epithelial Basal Cells Are Distinct from Dendritic Cells and Macrophages in the Mouse Epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article DE basal cells; dendritic cells; epididymis; immunology; macrophages; male reproductive tract; reproductive immunology ID MALE REPRODUCTIVE-TRACT; TRANSCRIPTION FACTOR FOXI1; LUMINAL ACIDIFICATION; POSTNATAL-DEVELOPMENT; RAT EPIDIDYMIS; STEM-CELLS; V-ATPASE; IN-VIVO; MOLECULAR SIGNATURES; REGIONAL-VARIATION AB The epithelium that lines the epididymal duct establishes the optimal milieu in which spermatozoa mature, acquire motility, and are stored. This finely tuned environment also protects antigenic sperm against pathogens and autoimmunity, which are potential causes of transient or permanent infertility. The epididymal epithelium is pseudostratified and contains basal cells (BCs) that are located beneath other epithelial cells. Previous studies showed that in the mouse epididymis, BCs possess macrophage-like characteristics. However, we previously identified a dense population of cells belonging to the mononuclear phagocyte (MP) system (comprised of macrophages and dendritic cells) in the basal compartment of the mouse epididymis and showed that a subset of MPs express the macrophage marker F4/80. In the present study, we evaluate the distribution of BCs and MPs in the epididymis of transgenic CD11c-EYFP mice, in which EYFP is expressed exclusively in MPs, using antibodies against the BC marker keratin 5 (KRT5) and the macrophage marker F4/80. Immunofluorescence labeling for laminin, a basement membrane marker, showed that BCs and most MPs are located in the basal region of the epithelium. Confocal microscopy showed that in the initial segment, both BCs and MPs project intraepithelial extensions and establish a very intricate network. Flow cytometry experiments demonstrated that epididymal MPs and BCs are phenotypically distinct. BCs do not express F4/80, and MPs do not express KRT5. Therefore, despite their proximity and some morphological similarities with peritubular macrophages and dendritic cells, BCs do not belong to the MP system. C1 [Shum, Winnie W.; Smith, Tegan B.; Grigoryeva, Lubov S.; Roy, Jeremy W.; Hill, Eric; Breton, Sylvie; Da Silva, Nicolas] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Shum, Winnie W.; Smith, Tegan B.; Cortez-Retamozo, Virna; Grigoryeva, Lubov S.; Roy, Jeremy W.; Hill, Eric; Pittet, Mikael J.; Breton, Sylvie; Da Silva, Nicolas] Harvard Univ, Sch Med, Boston, MA USA. [Shum, Winnie W.; Smith, Tegan B.; Cortez-Retamozo, Virna; Grigoryeva, Lubov S.; Roy, Jeremy W.; Hill, Eric; Pittet, Mikael J.; Breton, Sylvie; Da Silva, Nicolas] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Da Silva, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Program Membrane Biol, 185 Cambridge St,CPZN 8-218, Boston, MA 02114 USA. EM dasilva.nicolas@mgh.harvard.edu FU National Institutes of Health [R01HD069623, RO1DK085715, R01AI084880]; Boston Area Diabetes and Endocrinology Research Center [DK057521]; MGH Center for the Study of Inflammatory Bowel Disease [DK043351] FX Supported by National Institutes of Health grants R01HD069623 (N.D.S.), RO1DK085715 (S.B.), and R01AI084880 (M.J.P.). S.B. is a Massachusetts General Hospital ( MGH) Charles and Ann Sanders Research Scholar. The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK057521) and the MGH Center for the Study of Inflammatory Bowel Disease (DK043351). NR 69 TC 11 Z9 11 U1 0 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 2014 VL 90 IS 5 AR 90 DI 10.1095/biolreprod.113.116681 PG 10 WC Reproductive Biology SC Reproductive Biology GA AH3NU UT WOS:000336031600001 PM 24648397 ER PT J AU Martinod, K Wagner, DD AF Martinod, Kimberly Wagner, Denisa D. TI Thrombosis: tangled up in NETs SO BLOOD LA English DT Review ID NEUTROPHIL EXTRACELLULAR TRAPS; VON-WILLEBRAND-FACTOR; DEEP-VEIN THROMBOSIS; MYOCARDIAL ISCHEMIA/REPERFUSION INJURY; GROUP-A STREPTOCOCCUS; VENOUS THROMBOSIS; IN-VIVO; DNA TRAPS; PLASMA FIBRONECTIN; INNATE IMMUNITY AB The contributions by blood cells to pathological venous thrombosis were only recently appreciated. Both platelets and neutrophils are now recognized as crucial for thrombus initiation and progression. Here we review the most recent findings regarding the role of neutrophil extracellular traps (NETs) in thrombosis. We describe the biological process of NET formation (NETosis) and how the extracellular release of DNA and protein components of NETs, such as histones and serine proteases, contributes to coagulation and platelet aggregation. Animal models have unveiled conditions in which NETs form and their relation to thrombogenesis. Genetically engineered mice enable further elucidation of the pathways contributing to NETosis at the molecular level. Peptidylarginine deiminase 4, an enzyme that mediates chromatin decondensation, was identified to regulate both NETosis and pathological thrombosis. A growing body of evidence reveals that NETs also form in human thrombosis and that NET biomarkers in plasma reflect disease activity. The cell biology of NETosis is still being actively characterized and may provide novel insights for the design of specific inhibitory therapeutics. After a review of the relevant literature, we propose new ways to approach thrombolysis and suggest potential prophylactic and therapeutic agents for thrombosis. C1 [Martinod, Kimberly] Harvard Univ, Sch Med, Grad Program Immunol, Div Med Sci, Boston, MA USA. [Martinod, Kimberly; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM denisa.wagner@childrens.harvard.edu OI Martinod, Kimberly/0000-0002-1026-6107 FU National Heart, Lung, and Blood Institute [R01HL095091, R01HL041002, R01HL102101] FX This work was supported by National Heart, Lung, and Blood Institute grants R01HL095091, R01HL041002, and R01HL102101 (to D.D.W.). NR 127 TC 109 Z9 111 U1 3 U2 21 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 2014 VL 123 IS 18 BP 2768 EP 2776 DI 10.1182/blood-2013-10-463646 PG 9 WC Hematology SC Hematology GA AH1QP UT WOS:000335896300010 PM 24366358 ER PT J AU Treon, SP Cao, Y Xu, L Yang, G Liu, X Hunter, ZR AF Treon, Steven P. Cao, Yang Xu, Lian Yang, Guang Liu, Xia Hunter, Zachary R. TI Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; WHIM SYNDROME; L265P; LYMPHOMA; FEATURES; CELLS AB Whole genome sequencing has revealed activating somatic mutations in MYD88 (L265P) and CXCR4 in Waldenstrom macroglobulinemia (WM). CXCR4 somatic mutations in WM are the first ever reported in human cancer and are similar to nonsense (NS) and frameshift (FS) germline mutations found in warts, hypogammaglobulinemia, infections and myelokathexis (WHIM) syndrome. We genotyped lymphoplasmacytic cells from 175 WM patients and observed significantly higher bone marrow (BM) disease involvement, serum immunoglobulin-M levels, and symptomatic disease requiring therapy, including hyperviscosity syndrome in those patients with MYD88(L265P) CXCR4(WHIM/NS) mutations (P < .03). Patients with MYD88(L265P) CXCR4(WHIM/FS) or MYD88(L265P) CXCR4 WILDTYPE (WT) had intermediate BM and serum immunoglobulin-M levels; those with MYD88(WT) CXCR4(WT) showed lowest BM disease burden. Fewer patients with MYD88(L265P) and CXCR4(WHIM/FS or NS) vs MYD88(L265P) CXCR4(WT) presented with adenopathy (P < .01), further delineating differences in disease tropism based on CXCR4 status. Neither MYD88 nor CXCR4 mutations correlated with SDF-1a (RS1801157) polymorphisms in 54 patients who were genotyped for these variants. Unexpectedly, risk of death was not impacted by CXCR4 mutation status, but by MYD88(WT) status (hazard ratio 10.54; 95% confidence interval 2.4-46.2, P = .0018). Somatic mutations in MYD88 and CXCR4 are important determinants of clinical presentation and impact overall survival in WM. Targeted therapies directed against MYD88 and/or CXCR4 signaling may provide a personalized treatment approach to WM. C1 [Treon, Steven P.; Cao, Yang; Xu, Lian; Yang, Guang; Liu, Xia; Hunter, Zachary R.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Treon, Steven P.; Cao, Yang; Xu, Lian; Yang, Guang; Liu, Xia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hunter, Zachary R.] Boston Univ, Grad Sch Med Sci, Dept Pathol, Boston, MA 02215 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M548,450 Brookline Ave, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU Peter and Helen Bing Foundation; International Waldenstrom's Macroglobulinemia Foundation; Coyote Fund for WM; D'Amato Family Fund for Genomic Discovery; Edward and Linda Nelson Fund for WM Research FX This study was supported by the Peter and Helen Bing Foundation, the International Waldenstrom's Macroglobulinemia Foundation, the Coyote Fund for WM, the D'Amato Family Fund for Genomic Discovery, and the Edward and Linda Nelson Fund for WM Research. NR 22 TC 66 Z9 67 U1 2 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 2014 VL 123 IS 18 BP 2791 EP 2796 DI 10.1182/blood-2014-01-550905 PG 6 WC Hematology SC Hematology GA AH1QP UT WOS:000335896300013 PM 24553177 ER PT J AU Adamia, S Bar-Natan, M Haibe-Kains, B Pilarski, PM Bach, C Pevzner, S Calimeri, T Avet-Loiseau, H Lode, L Verselis, S Fox, EA Galinsky, I Mathews, S Dagogo-Jack, I Wadleigh, M Steensma, DP Motyckova, G Deangelo, DJ Quackenbush, J Tenen, DG Stone, RM Griffin, JD AF Adamia, Sophia Bar-Natan, Michal Haibe-Kains, Benjamin Pilarski, Patrick M. Bach, Christian Pevzner, Samuel Calimeri, Teresa Avet-Loiseau, Herve Lode, Laurence Verselis, Sigitas Fox, Edward A. Galinsky, Ilene Mathews, Steven Dagogo-Jack, Ibiayi Wadleigh, Martha Steensma, David P. Motyckova, Gabriela Deangelo, Daniel J. Quackenbush, John Tenen, Daniel G. Stone, Richard M. Griffin, James D. TI NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML SO BLOOD LA English DT Article ID MUTATIONS; DISEASE; DIFFERENTIATION; EXPRESSION; ISOFORM; MARKERS; VARIANT; GENOME AB Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34(+) bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (> 70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics. C1 [Adamia, Sophia; Calimeri, Teresa; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Quackenbush, John; Stone, Richard M.; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Bar-Natan, Michal; Bach, Christian; Tenen, Daniel G.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Bioinformat & Computat Genom Lab, Montreal, PQ H2W 1R7, Canada. [Pilarski, Patrick M.] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada. [Pevzner, Samuel] Boston Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02118 USA. [Pevzner, Samuel] Boston Univ, Sch Med, Dept Genet, Boston, MA 02118 USA. [Calimeri, Teresa] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Calimeri, Teresa] Tommaso Campanella Canc Ctr, Catanzaro, Italy. [Avet-Loiseau, Herve] Ctr Hosp Univ Rangueil, Univ Hosp, Unite Genom Myelome, Lab Unite Genom Myelome, Toulouse, France. [Lode, Laurence] Univ Hosp, Hematol Lab, Nantes, France. [Lode, Laurence] INSERM, U892, Nantes, France. [Verselis, Sigitas; Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02215 USA. [Galinsky, Ilene; Mathews, Steven; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Stone, Richard M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02215 USA. [Dagogo-Jack, Ibiayi] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Adamia, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM sophia_adamia@dfci.harvard.edu; James_Griffin@harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011; OI Bach, Christian/0000-0003-4675-7896; Haibe-Kains, Benjamin/0000-0002-7684-0079; Tenen, Daniel/0000-0002-6423-3888 FU National Cancer Institute [PO1CA66996-13]; American Society of Hematology scholar award for Clinical/Translational Research; American Association for Cancer Research-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research; National Library of Medicine of the National Institutes of Health [R01 LM010129-01]; Institut de Recherches Cliniques de Montreal; Alberta Innovates Centre for Machine Learning; German Research Foundation (DFG) [BA 4186/1-1] FX This study was supported in part by National Cancer Institute grant PO1CA66996-13. S.A. is supported by the American Society of Hematology scholar award for Clinical/Translational Research and supported by the American Association for Cancer Research-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research. J.Q. was supported by National Library of Medicine of the National Institutes of Health grant R01 LM010129-01. B.H.-K. was supported by internal funding at the Institut de Recherches Cliniques de Montreal. P.M.P. is supported by the Alberta Innovates Centre for Machine Learning. C.B. was supported by the German Research Foundation (DFG Fellowship BA 4186/1-1). NR 39 TC 13 Z9 13 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 2014 VL 123 IS 18 BP 2816 EP 2825 DI 10.1182/blood-2013-02-481507 PG 10 WC Hematology SC Hematology GA AH1QP UT WOS:000335896300016 PM 24574459 ER PT J AU Elbogen, EB Johnson, SC Wagner, HR Sullivan, C Taft, CT Beckham, JC AF Elbogen, Eric B. Johnson, Sally C. Wagner, H. Ryan Sullivan, Connor Taft, Casey T. Beckham, Jean C. TI Violent behaviour and post-traumatic stress disorder in US Iraq and Afghanistan veterans SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID INTIMATE PARTNER VIOLENCE; UK MILITARY PERSONNEL; MENTAL-HEALTH PROBLEMS; RISK-ASSESSMENT; COMBAT; WAR; AGGRESSION; FORCES; SAMPLE; PTSD AB Background Violence towards others in the community has been identified as a significant problem for a subset of Iraq and Afghanistan veterans. Aims To investigate the extent to which post-traumatic stress disorder (PTSD) and other risk factors predict future violent behaviour in military veterans. Method A national, multiwave survey enrolling a random sample of all US veterans who served in the military after 11 September 2001 was conducted. A total of 1090 veterans from 50 US states and all military branches completed two survey waves mailed 1 year apart (retention rate=79%). Results Overall, 9% endorsed engaging in severe violence and 26% in other physical aggression in the previous year, as measured at Wave 2. Younger age, financial instability, history of violence before military service, higher combat exposure, PTSD, and alcohol misuse at Wave 1 were significantly associated with higher severe violence and other physical aggression in the past year at Wave 2. When combinations of these risk factors were present, predicted probability of violence in veterans rose sharply. Veterans with both PTSD and alcohol misuse had a substantially higher rate of subsequent severe violence (35.9%) compared with veterans with alcohol misuse without PTSD (10.6%), PTSD without alcohol misuse (10.0%) or neither PTSD nor alcohol misuse (5.3%). Using multiple regression, we found that veterans with PTSD and without alcohol misuse were not at significantly higher risk of severe violence than veterans with neither PTSD nor alcohol misuse. There was a trend for other physical aggression to be higher in veterans with PTSD without alcohol misuse. Conclusions Co-occurring PTSD and alcohol misuse was associated with a marked increase in violence and aggression in veterans. Compared with veterans with neither PTSD nor alcohol misuse, veterans with PTSD and no alcohol misuse were not significantly more likely to be severely violent and were only marginally more likely to engage in other physical aggression. Attention to cumulative effects of multiple risk factors beyond diagnosis - including demographics, violence history, combat exposure, and veterans' having money to cover basic needs like food, shelter, transportation, and medical care - is crucial for optimising violence risk management. C1 [Elbogen, Eric B.; Johnson, Sally C.; Sullivan, Connor] Univ N Carolina, Sch Med, Dept Psychiat, Forens Psychiat Program & Clin, Chapel Hill, NC 27599 USA. [Elbogen, Eric B.] Durham VA Med Ctr, Midatlantic Mental Illness Res Educ & Clin Ctr MI, Durham, NC USA. [Wagner, H. Ryan; Beckham, Jean C.] Durham VA Med Ctr, MIRECC, Durham, NC USA. [Wagner, H. Ryan; Beckham, Jean C.] Duke Univ, Dept Psychiat, Sch Med, Durham, NC 27706 USA. [Taft, Casey T.] VA Boston Healthcare, VA Natl Ctr PTSD, Psychol Serv, Boston, MA USA. [Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Elbogen, EB (reprint author), Univ N Carolina, Box 7160, Chapel Hill, NC 27599 USA. EM eric.elbogen@unc.edu FU US National Institute of Mental Health (NIMH); NIMH [R01MH080988]; Office for Research and Development Clinical Science and Health Services, Department of Veterans Affairs; Mid-Atlantic Mental Illness Research, Education and Clinical Center FX The US National Institute of Mental Health (NIMH) funded this project. The US Department of Veterans Affairs provided infrastructure to conduct the project. The authors' work on this manuscript was independent of the US NIMH and US Department of Veterans Affairs, which had no role in the analysis, interpretation or decision to submit this research report Preparation of this manuscript was supported by the NIMH (R01MH080988), the Office for Research and Development Clinical Science and Health Services, Department of Veterans Affairs, and the Mid-Atlantic Mental Illness Research, Education and Clinical Center. NR 43 TC 13 Z9 13 U1 2 U2 22 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 2014 VL 204 IS 5 BP 368 EP 375 DI 10.1192/bjp.bp.113.134627 PG 8 WC Psychiatry SC Psychiatry GA AH3HY UT WOS:000336015500010 PM 24578444 ER PT J AU Pietrzak, RH Scott, JC Neumeister, A Lim, YY Ames, D Ellis, KA Harrington, K Lautenschlager, NT Szoeke, C Martins, RN Masters, CL Villemagne, VL Rowe, CC Maruff, P AF Pietrzak, Robert H. Scott, J. Cobb Neumeister, Alexander Lim, Yen Ying Ames, David Ellis, Kathryn A. Harrington, Karra Lautenschlager, Nicola T. Szoeke, Cassandra Martins, Ralph N. Masters, Colin L. Villemagne, Victor L. Rowe, Christopher C. Maruff, Paul CA Australian Imaging Biomarkers TI Anxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID COGNITIVE IMPAIRMENT; DEPRESSION AB Although beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d=0.65) and episodic (Cohen's d=0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid. C1 [Pietrzak, Robert H.; Scott, J. Cobb] VA Connecticut Healthcare Syst, Clin Neurosci Div, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Pietrzak, Robert H.; Scott, J. Cobb] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Neumeister, Alexander] NYU, Dept Radiol, Sch Med, New York, NY 10016 USA. [Lim, Yen Ying; Ellis, Kathryn A.; Harrington, Karra; Masters, Colin L.; Villemagne, Victor L.; Maruff, Paul] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. [Ames, David; Ellis, Kathryn A.] Univ Melbourne, Kew & Natl Ageing Res Inst, Dept Psychiat, Acad Unit Psychiat Old Age,St Vincents Hlth, Parkville, Vic 3052, Australia. [Lautenschlager, Nicola T.] Univ Melbourne, Dept Psychiat, Acad Unit Psychiat Old Age, St Vincents Hlth, Kew, Vic, Australia. [Lautenschlager, Nicola T.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. [Lautenschlager, Nicola T.] Univ Western Australia, WA Ctr Hlth & Ageing, Perth, WA 6009, Australia. [Szoeke, Cassandra] Natl Ageing Res Inst, Parkville, Vic, Australia. [Szoeke, Cassandra] Univ Melbourne, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Szoeke, Cassandra] CSIRO Preventat Hlth Flagship, Parkville, Vic, Australia. [Martins, Ralph N.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res & Care, Perth, WA, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Heidelberg, Vic, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Austin Hlth, Ctr PET, Heidelberg, Vic, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Univ Melbourne, Austin Hlth, Dept Med, Heidelberg, Vic, Australia. [Maruff, Paul] Cog State Ltd, Melbourne, Vic, Australia. RP Pietrzak, RH (reprint author), VA Connecticut Healthcare Syst, Natl Ctr PTSD, 950 Campbell Ave 161E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu OI Maruff, Paul/0000-0002-6947-9537; Szoeke, Cassandra/0000-0002-3698-2590 NR 10 TC 8 Z9 8 U1 0 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 2014 VL 204 IS 5 BP 400 EP 401 DI 10.1192/bjp.bp.113.134239 PG 2 WC Psychiatry SC Psychiatry GA AH3HY UT WOS:000336015500015 PM 24526746 ER PT J AU Wagle, N Grabiner, BC Van Allen, EM Hodis, E Jacobus, S Supko, JG Stewart, M Choueiri, TK Gandhi, L Cleary, JM Elfiky, AA Taplin, ME Stack, EC Signoretti, S Loda, M Shapiro, GI Sabatini, DM Lander, ES Gabriel, SB Kantoff, PW Garraway, LA Rosenberg, JE AF Wagle, Nikhil Grabiner, Brian C. Van Allen, Eliezer M. Hodis, Eran Jacobus, Susanna Supko, Jeffrey G. Stewart, Michelle Choueiri, Toni K. Gandhi, Leena Cleary, James M. Elfiky, Aymen A. Taplin, Mary Ellen Stack, Edward C. Signoretti, Sabina Loda, Massimo Shapiro, Geoffrey I. Sabatini, David M. Lander, Eric S. Gabriel, Stacey B. Kantoff, Philip W. Garraway, Levi A. Rosenberg, Jonathan E. TI Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib SO CANCER DISCOVERY LA English DT Article ID TUBEROUS SCLEROSIS; SOLID TUMORS; CANCER; SIROLIMUS; LYMPHANGIOLEIOMYOMATOSIS; ANGIOMYOLIPOMA; HETEROGENEITY; SENSITIVITY; INHIBITION; RAPAMYCIN AB Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders : rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors. Whole-exome sequencing of a patient with a 14-month complete response on this trial revealed two concurrent mutations in mTOR, the target of everolimus. In vitro experiments demonstrate that both mutations are activating, suggesting a biologic mechanism for exquisite sensitivity to everolimus in this patient. The use of precision (or "personalized") medicine approaches to screen patients with cancer for alterations in the mTOR pathway may help to identify subsets of patients who may benefit from targeted therapies directed against mTOR. SIGNIFICANCE: The study of exceptional responders represents a promising approach to better understanding the mechanisms that underlie sensitivity to targeted anticancer therapies. Here, we identify two activating mTOR mutations in a patient with exquisite sensitivity to everolimus and pazopanib, suggesting an approach to identifying patients who might benefit most from mTOR inhibitors. (C) 2014 AACR. C1 [Wagle, Nikhil; Van Allen, Eliezer M.; Choueiri, Toni K.; Gandhi, Leena; Cleary, James M.; Elfiky, Aymen A.; Taplin, Mary Ellen; Stack, Edward C.; Signoretti, Sabina; Loda, Massimo; Shapiro, Geoffrey I.; Kantoff, Philip W.; Garraway, Levi A.; Rosenberg, Jonathan E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jacobus, Susanna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Stack, Edward C.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Wagle, Nikhil; Van Allen, Eliezer M.; Choueiri, Toni K.; Gandhi, Leena; Cleary, James M.; Elfiky, Aymen A.; Taplin, Mary Ellen; Shapiro, Geoffrey I.; Kantoff, Philip W.; Garraway, Levi A.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Stack, Edward C.; Signoretti, Sabina; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Supko, Jeffrey G.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Wagle, Nikhil; Van Allen, Eliezer M.; Hodis, Eran; Stewart, Michelle; Loda, Massimo; Sabatini, David M.; Lander, Eric S.; Gabriel, Stacey B.; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Grabiner, Brian C.; Sabatini, David M.] Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA 02142 USA. [Grabiner, Brian C.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D1542, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu; rosenbj1@mskcc.org OI Rosenberg, Jonathan/0000-0003-2637-4249; Gandhi, Leena/0000-0002-2398-9179 FU Next Generation Fund at the Broad Institute of MIT and Harvard; National Institute of Health [T32GM007753]; National Human Genome Research Institute [5U54HG003067-11]; GlaxoSmithkline; Novartis FX This work was supported by The Next Generation Fund at the Broad Institute of MIT and Harvard (to N. Wagle), the National Institute of Health T32GM007753 (to E. Hodis), the National Human Genome Research Institute 5U54HG003067-11 (to E.S. Lander, S.B. Gabriel, and L.A. Garraway), GlaxoSmithkline (to T.K. Choueiri and J.E. Rosenberg), and Novartis (to J.G. Supko, T.K. Choueiri, and J.E. Rosenberg). NR 24 TC 102 Z9 103 U1 0 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2014 VL 4 IS 5 BP 546 EP 553 DI 10.1158/2159-8290.CD-13-0353 PG 8 WC Oncology SC Oncology GA AH1ZA UT WOS:000335919200025 PM 24625776 ER PT J AU Grabiner, BC Nardi, V Birsoy, K Possemato, R Shen, K Sinha, S Jordan, A Beck, AH Sabatini, DM AF Grabiner, Brian C. Nardi, Valentina Birsoy, Kivan Possemato, Richard Shen, Kuang Sinha, Sumi Jordan, Alexander Beck, Andrew H. Sabatini, David M. TI A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity SO CANCER DISCOVERY LA English DT Article ID RENAL-CELL CARCINOMA; SOMATIC MUTATIONS; RAG GTPASES; KINASE; GROWTH; HETEROGENEITY; ACTIVATION; RESISTANCE; INHIBITORS; DISCOVERY AB Genes encoding components of the PI3K-AKT-mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency. SIGNIFICANCE: We report that a diverse set of cancer-associated MTOR mutations confer increased mTORC1/2 pathway activity and that cells harboring these mutations are highly sensitive to rapamycin in culture and in vivo. These findings are clinically relevant as the MTOR mutations characterized herein may serve as biomarkers for predicting tumor responses to mTOR inhibitors. (C) 2014 AACR. C1 [Grabiner, Brian C.; Birsoy, Kivan; Possemato, Richard; Shen, Kuang; Sinha, Sumi; Jordan, Alexander; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Grabiner, Brian C.; Birsoy, Kivan; Possemato, Richard; Shen, Kuang; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Grabiner, Brian C.; Birsoy, Kivan; Possemato, Richard; Shen, Kuang; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Grabiner, Brian C.; Birsoy, Kivan; Possemato, Richard; Shen, Kuang; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Grabiner, Brian C.; Birsoy, Kivan; Possemato, Richard; Shen, Kuang; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Nardi, Valentina] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Pathol,Med Sch, Boston, MA 02114 USA. [Beck, Andrew H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, Nine Cambridge Ctr, Cambridge, MA 02142 USA. EM sabatini@wi.mit.edu RI Shen, Kuang/H-9441-2016; OI Possemato, Richard/0000-0002-2401-0030 FU American Cancer Society [118855-PF-10-069-01-TBG]; Leukemia and Lymphoma Society; Jane Coffin Childs Fund; NIH [K99 CA168940, CA103866, CA129105, AI07389]; Starr Cancer Consortium; David H. Koch Institute for Integrative Cancer Research at MIT; Alexander and Margaret Stewart Trust Fund FX This research is supported in part by a postdoctoral fellowship (#118855-PF-10-069-01-TBG) from The American Cancer Society (to B.C. Grabiner), The Leukemia and Lymphoma Society and The Jane Coffin Childs Fund (to K. Birsoy), NIH K99 CA168940 (to R. Possemato), and grants from the Starr Cancer Consortium, the David H. Koch Institute for Integrative Cancer Research at MIT, The Alexander and Margaret Stewart Trust Fund, and the NIH (CA103866, CA129105, and AI07389) to D.M. Sabatini. D.M. Sabatini is an investigator of the Howard Hughes Medical Institute. NR 41 TC 78 Z9 78 U1 2 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2014 VL 4 IS 5 BP 554 EP 563 DI 10.1158/2159-8290.CD-13-0929 PG 10 WC Oncology SC Oncology GA AH1ZA UT WOS:000335919200026 PM 24631838 ER PT J AU Purrington, KS Slager, S Eccles, D Yannoukakos, D Fasching, PA Miron, P Carpenter, J Chang-Claude, J Martin, NG Montgomery, GW Kristensen, V Anton-Culver, H Goodfellow, P Tapper, WJ Rafiq, S Gerty, SM Durcan, L Konstantopoulou, I Fostira, F Vratimos, A Apostolou, P Konstanta, I Kotoula, V Lakis, S Dimopoulos, MA Skarlos, D Pectasides, D Fountzilas, G Beckmann, MW Hein, A Ruebner, M Ekici, AB Hartmann, A Schulz-Wendtland, R Renner, SP Janni, W Rack, B Scholz, C Neugebauer, J Andergassen, U Lux, MP Haeberle, L Clarke, C Pathmanathan, N Rudolph, A Flesch-Janys, D Nickels, S Olson, JE Ingle, JN Olswold, C Slettedahl, S Eckel-Passow, JE Anderson, SK Visscher, DW Cafourek, VL Sicotte, H Prodduturi, N Weiderpass, E Bernstein, L Ziogas, A Ivanovich, J Giles, GG Baglietto, L Southey, M Kosma, VM Fischer, HP Reed, MWR Cross, SS Deming-Halverson, S Shrubsole, M Cai, QY Shu, XO Daly, M Weaver, J Ross, E Klemp, J Sharma, P Torres, D Rudiger, T Wolfing, H Ulmer, HU Forsti, A Khoury, T Kumar, S Pilarski, R Shapiro, CL Greco, D Heikkila, P Aittomaki, K Blomqvist, C Irwanto, A Liu, JJ Pankratz, VS Wang, XS Severi, G Mannermaa, A Easton, D Hall, P Brauch, H Cox, A Zheng, W Godwin, AK Hamann, U Ambrosone, C Toland, AE Nevanlinna, H Vachon, CM Fergus, J AF Purrington, Kristen S. Slager, Susan Eccles, Diana Yannoukakos, Drakoulis Fasching, Peter A. Miron, Penelope Carpenter, Jane Chang-Claude, Jenny Martin, Nicholas G. Montgomery, Grant W. Kristensen, Vessela Anton-Culver, Hoda Goodfellow, Paul Tapper, William J. Rafiq, Sajjad Gerty, Susan M. Durcan, Lorraine Konstantopoulou, Irene Fostira, Florentia Vratimos, Athanassios Apostolou, Paraskevi Konstanta, Irene Kotoula, Vassiliki Lakis, Sotiris Dimopoulos, Meletios A. Skarlos, Dimosthenis Pectasides, Dimitrios Fountzilas, George Beckmann, Matthias W. Hein, Alexander Ruebner, Matthias Ekici, Arif B. Hartmann, Arndt Schulz-Wendtland, Ruediger Renner, Stefan P. Janni, Wolfgang Rack, Brigitte Scholz, Christoph Neugebauer, Julia Andergassen, Ulrich Lux, Michael P. Haeberle, Lothar Clarke, Christine Pathmanathan, Nirmala Rudolph, Anja Flesch-Janys, Dieter Nickels, Stefan Olson, Janet E. Ingle, James N. Olswold, Curtis Slettedahl, Seth Eckel-Passow, Jeanette E. Anderson, S. Keith Visscher, Daniel W. Cafourek, Victoria L. Sicotte, Hugues Prodduturi, Naresh Weiderpass, Elisabete Bernstein, Leslie Ziogas, Argyrios Ivanovich, Jennifer Giles, Graham G. Baglietto, Laura Southey, Melissa Kosma, Veli-Matti Fischer, Hans-Peter Reed, Malcom W. R. Cross, Simon S. Deming-Halverson, Sandra Shrubsole, Martha Cai, Qiuyin Shu, Xiao-Ou Daly, Mary Weaver, JoEllen Ross, Eric Klemp, Jennifer Sharma, Priyanka Torres, Diana Rudiger, Thomas Wolfing, Heidrun Ulmer, Hans-Ulrich Forsti, Asta Khoury, Thaer Kumar, Shicha Pilarski, Robert Shapiro, Charles L. Greco, Dario Heikkila, Paivi Aittomaki, Kristiina Blomqvist, Carl Irwanto, Astrid Liu, Jianjun Pankratz, Vernon Shane Wang, Xianshu Severi, Gianluca Mannermaa, Arto Easton, Douglas Hall, Per Brauch, Hiltrud Cox, Angela Zheng, Wei Godwin, Andrew K. Hamann, Ute Ambrosone, Christine Toland, Amanda Ewart Nevanlinna, Heli Vachon, Celine M. Couch, Fergus J. CA GENICA Network TI Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer SO CARCINOGENESIS LA English DT Article ID ESTROGEN-RECEPTOR; EXPRESSION; VARIANTS; CONSORTIUM; PROTEIN; CELLS; TBX3 AB In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction. C1 [Purrington, Kristen S.; Slager, Susan; Olson, Janet E.; Olswold, Curtis; Slettedahl, Seth; Eckel-Passow, Jeanette E.; Anderson, S. Keith; Cafourek, Victoria L.; Sicotte, Hugues; Prodduturi, Naresh; Pankratz, Vernon Shane; Vachon, Celine M.; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Eccles, Diana; Tapper, William J.; Rafiq, Sajjad; Gerty, Susan M.; Durcan, Lorraine] Univ Southampton IBJ, Fac Med, Southampton, Hants, England. [Yannoukakos, Drakoulis; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Apostolou, Paraskevi; Konstanta, Irene] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab INRASTES, Athens 15310, Greece. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ruebner, Matthias; Renner, Stefan P.; Lux, Michael P.; Haeberle, Lothar] Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, D-91012 Erlangen, Germany. [Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ruebner, Matthias; Renner, Stefan P.; Lux, Michael P.; Haeberle, Lothar] Univ Erlangen Nurnberg, D-91012 Erlangen, Germany. [Miron, Penelope] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Carpenter, Jane] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Westmead, NSW 2145, Australia. [Chang-Claude, Jenny; Rudolph, Anja; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, QIMR GWAS Collect, Brisbane, Qld 4006, Australia. [Kristensen, Vessela] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Department Genet, N-0316 Oslo, Norway. [Kristensen, Vessela] Univ Oslo, Fac Med, Fac Div Ahus, N-0316 Oslo, Norway. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA. [Goodfellow, Paul; Ivanovich, Jennifer] Washington Univ, Barnes Jewish Hosp, Sch Med, St Louis, MO 63110 USA. [Goodfellow, Paul; Ivanovich, Jennifer] Siteman Canc Ctr, St Louis, MO 63110 USA. [Kotoula, Vassiliki] Aristotle Univ Thessaloniki, Mol Oncol Lab, Dept Pathol, Thessaloniki 54124, Greece. [Lakis, Sotiris] Aristotle Univ Thessaloniki, Lab Mol Oncol, Thessaloniki 54124, Greece. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Alexandra Hosp, GR-11527 Athens, Greece. [Skarlos, Dimosthenis] Metropolitan Hosp, Dept Med Oncol 2, Athens 15125, Greece. [Pectasides, Dimitrios] Univ Athens, Sch Med, Hippokrat Hosp, Dept Internal Med 2,Oncol Sect, GR-11527 Athens, Greece. [Fountzilas, George] Aristotle Univ Thessaloniki, Sch Med, Papageorgiou Hosp, Dept Med Oncol, Thessaloniki 54124, Greece. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91012 Erlangen, Germany. [Hartmann, Arndt] Univ Erlangen Nurnberg, Inst Pathol, D-91012 Erlangen, Germany. [Schulz-Wendtland, Ruediger] Univ Erlangen Nurnberg, Inst Diagnost Radiol, D-91012 Erlangen, Germany. [Janni, Wolfgang; Scholz, Christoph] Univ Hosp Ulm, Dept Gynecol & Obstet, D-89069 Ulm, Germany. [Rack, Brigitte; Neugebauer, Julia; Andergassen, Ulrich] Univ Munich, Dept Gynecol & Obstet, Univ Hosp, D-80539 Munich, Germany. [Clarke, Christine] Univ Sydney, Westmead Inst Canc Res, Sydney Med Sch Westmead, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Pathmanathan, Nirmala] Westmead Hosp, Westmead Breast Canc Inst, Westmead, NSW 2145, Australia. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Ingle, James N.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Visscher, Daniel W.; Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Visscher, Daniel W.; Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Weiderpass, Elisabete] Univ Tromso, Dept Community Med, N-9019 Tromso, Norway. [Weiderpass, Elisabete] Folkh lsan Res Canc Ctr, Helsinki 00250, Finland. [Weiderpass, Elisabete] Canc Registry Norway, N-0304 Oslo, Norway. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia. [Southey, Melissa] Univ Melbourne, Dept Pathol, Melbourne, Vic 3053, Australia. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Kuopio Univ Hosp, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio 80130, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Kuopio Univ Hosp, Bioctr Kuopio, Canc Ctr Eastern Finland & Imaging Ctr,Dept Clin, Kuopio 80130, Finland. [Fischer, Hans-Peter] Univ Bonn, Dep Pathol, Fac Med, D-53127 Bonn, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. Evangel Kliniken Bonn gGmbH, Dept Internal Med, D-53127 Bonn, Germany. Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, D-20246 Hamburg, Germany. Inst Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, D-44789 Bochum, Germany. Univ Bonn, Inst Pathol, Fac Med, D-53127 Bonn, Germany. [Torres, Diana; Hamann, Ute; GENICA Network] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Reed, Malcom W. R.; Cox, Angela] Univ Sheffield, Dept Oncol, Canc Res UK, Yorkshire Canc Res Sheffield Canc Res Ctr, Sheffield S10 2TN, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Sheffield S10 2TN, S Yorkshire, England. [Deming-Halverson, Sandra; Shrubsole, Martha; Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN 37232 USA. [Daly, Mary] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. [Weaver, JoEllen] Univ Penn, Sch Med, PennMed Biobank, Philadelphia, PA 19104 USA. [Ross, Eric] Fox Chase Canc Ctr, Dept Biostat & Bioinformat, Philadelphia, PA 19111 USA. [Klemp, Jennifer; Sharma, Priyanka] Univ Kansas, Med Ctr, Dept Oncol Hematol, Kansas City, KS 66160 USA. [Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota 11001000, DC, Colombia. [Rudiger, Thomas; Wolfing, Heidrun] Stadt Klinikum Karlsruhe, Inst Pathol, D-76133 Karlsruhe, Germany. [Ulmer, Hans-Ulrich] Frauenklin Stadtklin Baden Baden, D-76530 Baden Baden, Germany. [Forsti, Asta] Lund Univ, Ctr Primary Hlth Care Res, S-22363 Malmo, Sweden. [Forsti, Asta] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany. [Khoury, Thaer] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. [Kumar, Shicha] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Pilarski, Robert] Ohio State Univ, Dept Internal Med, Div Human Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Shapiro, Charles L.] Ohio State Univ, Dept Internal Med, Div Med Oncol, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Greco, Dario; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki 00014, Finland. [Heikkila, Paivi] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki 00014, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki 00014, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki 00014, Finland. [Irwanto, Astrid; Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore. [Easton, Douglas] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Hall, Per] Karolinska Inst, S-17177 Stockholm, Sweden. [Godwin, Andrew K.] Univ Kansas, Dept Pathol & Lab Med, Med Ctr, Kansas City, KS 66160 USA. [Ambrosone, Christine] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Toland, Amanda Ewart] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. RP Fergus, J (reprint author), Mayo Clin, Stabile 2-42,200 First St SW, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu RI Hein, Alexander/F-6999-2010; Pilarski, Robert/E-3871-2011; Shrubsole, Martha/K-5052-2015; Montgomery, Grant/B-7148-2008; Weiderpass, Elisabete/M-4029-2016; Renner, Stefan/F-1158-2014; OI Yannoukakos, Drakoulis/0000-0001-7509-3510; Giles, Graham/0000-0003-4946-9099; Martin, Nicholas/0000-0003-4069-8020; Nevanlinna, Heli/0000-0002-0916-2976; Rafiq, Sajjad/0000-0003-4873-4540; Cross, Simon/0000-0003-2044-1754; Cox, Angela/0000-0002-5138-1099; Hein, Alexander/0000-0003-2601-3398; Shrubsole, Martha/0000-0002-5591-7575; Montgomery, Grant/0000-0002-4140-8139; Weiderpass, Elisabete/0000-0003-2237-0128; Renner, Stefan/0000-0003-2057-1268; Konstantopoulou, Irene/0000-0002-0470-0309; Lux, Michael Patrick/0000-0002-2781-2178 FU Mayo Clinic Genotyping Core; Mayo Clinic Expression Core SKKDKFZS FX We acknowledge the support of the Mayo Clinic Genotyping Core and Mayo Clinic Expression Core SKKDKFZS. We are grateful to all the patients for their participation. We thank the physicians, other hospital staff and research assistants who contributed to the patient recruitment, data collection and sample preparation. KBCP thank Eija Myohanen and Helena Kemilainen for technical assistance. HEBCS thank research nurses Hanna Jantti and Irja Erkkila for their help with the patient data and samples and Drs Ari Ristimaki, Tuomas Heikkinen, Mira Heinonen and Laura Hautala for their help with the tumor marker and pathology information, and gratefully acknowledges the Finnish Cancer Registry for the cancer data. NR 30 TC 39 Z9 40 U1 1 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2014 VL 35 IS 5 BP 1012 EP 1019 DI 10.1093/carcin/bgt404 PG 8 WC Oncology SC Oncology GA AH3RW UT WOS:000336043800006 PM 24325915 ER PT J AU Lovly, CM Shaw, AT AF Lovly, Christine M. Shaw, Alice T. TI Molecular Pathways: Resistance to Kinase Inhibitors and Implications for Therapeutic Strategies SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; CHRONIC MYELOID-LEUKEMIA; RECEPTOR TYROSINE KINASE; CHROMOSOME-POSITIVE LEUKEMIAS; METASTATIC BREAST-CANCER; ACQUIRED-RESISTANCE; TUMOR MICROENVIRONMENT; GEFITINIB RESISTANCE; IMATINIB MESYLATE; EGFR AB The development of targeted therapies has revolutionized the treatment of cancer patients. The identification of "druggable" oncogenic kinases and the creation of small-molecule inhibitors designed to specifically target these mutant kinases have become an important therapeutic paradigm across several different malignancies. Often these inhibitors induce dramatic clinical responses in molecularly defined cohorts. However, resistance to such targeted therapies is an inevitable consequence of this therapeutic approach. Resistance can be either primary (de novo) or acquired. Mechanisms leading to primary resistance may be categorized as tumor intrinsic factors or as patient/drug-specific factors. Acquired resistance may bemediated by target genemodification, activation of "bypass tracks" that serve as compensatory signaling loops, or histologic transformation. This brief review is a snapshot of the complex problem of therapeutic resistance, with a focus on resistance to kinase inhibitors in EGF receptor mutant and ALK rearranged non-small cell lung cancer, BRAF-mutant melanoma, and BCR-ABL- positive chronic myeloid leukemia. We describe specific mechanisms of primary and acquired resistance and then review emerging strategies to delay or overcome drug resistance. (C) 2014 AACR. C1 [Lovly, Christine M.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Lovly, Christine M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM ashaw1@partners.org FU K12 CA [0906525]; Damon Runyon Clinical Investigator Award; [R01: 5R01CA164273- 03] FX This work was supported by K12 CA 0906525 and a Damon Runyon Clinical Investigator Award (to C.M.Lovly) and by R01: 5R01CA164273- 03 (to A.T.Shaw). NR 60 TC 45 Z9 47 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2014 VL 20 IS 9 BP 2249 EP 2256 DI 10.1158/1078-0432.CCR-13-1610 PG 8 WC Oncology SC Oncology GA AH1XN UT WOS:000335915200003 PM 24789032 ER PT J AU Haq, R Fisher, DE Widlund, HR AF Haq, Rizwan Fisher, David E. Widlund, Hans R. TI Molecular Pathways: BRAF Induces Bioenergetic Adaptation by Attenuating Oxidative Phosphorylation SO CLINICAL CANCER RESEARCH LA English DT Article ID THERAPEUTIC TARGET; CANCER-CELLS; BRAF(V600E) INHIBITION; PYRUVATE-DEHYDROGENASE; METASTATIC MELANOMA; THYROID-CARCINOMA; IMPROVED SURVIVAL; LINEAGE SURVIVAL; BREAST-CANCER; LUNG-CANCER AB Cancers acquire mutations in cooperating pathways that sustain their growth and survival. To support continued proliferation, tumor cells adapt their metabolism to balance energy production with their augmented biosynthetic needs. Although most normal differentiated cells use mitochondrial oxidative phosphorylation (OXPHOS) as the bioenergetic source, cancer cells have been proposed to rely principally on cytoplasmic glycolysis. The molecular basis for this shift, termed the Warburg effect, is the subject of intense investigation, because mechanistic understanding may lead to novel approaches to target the altered metabolism of cancer cells. Recently, mutations BRAF(V600E) have emerged as a major regulator of metabolic homeostasis. Melanoma cells may use a metabolic shift to circumvent BRAF(V600E)-induced senescence though limiting their reliance on OXPHOS and promote proliferation. Furthermore, BRAF(V600E) acts to suppress expression of the melanocyte master regulator microphthalmia-associated transcription factor (MITF) and the mitochondrial biogenesis coactivator PGC1 alpha. Accordingly, therapeutic inhibition of BRAF(V600E) reverses metabolic reprogramming in melanoma cells and elevates OXPHOS through increased MITF-PGC1 alpha levels. BRAF-targeted drugs modulate the metabolic state of malignant melanoma cells, and counteracting these adaptive responses using pharmacologic agents may prove useful in combinatorial therapeutic strategies. (C) 2014 AACR. C1 [Haq, Rizwan; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA USA. [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA. [Widlund, Hans R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol,Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. RP Widlund, HR (reprint author), Brigham & Womens Hosp, 77 Ave Louis Pasteur,Rm 671, Boston, MA 02115 USA. EM hwidlund@bics.bwh.harvard.edu FU American Skin Association; National Institutes of Health [R01AR043369]; Dermatology Foundation; Dr.Miriam and Sheldon G.Adelson Medical Research Foundation FX This work was supported in part by funds from the American Skin Association (to R.Haq), the Dr.Miriam and Sheldon G.Adelson Medical Research Foundation and National Institutes of Health under award number R01AR043369 (to D.E.Fisher), and the Dermatology Foundation (to H.R.Widlund). NR 67 TC 13 Z9 14 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2014 VL 20 IS 9 BP 2257 EP 2263 DI 10.1158/1078-0432.CCR-13-0898 PG 7 WC Oncology SC Oncology GA AH1XN UT WOS:000335915200004 PM 24610826 ER PT J AU DeLisi, LE AF DeLisi, Lynn E. TI Ethical issues in the use of genetic testing of patients with schizophrenia and their families SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE DNA; ethics; genome; pharmacogenetics; prediction ID INCIDENTAL FINDINGS; TARDIVE-DYSKINESIA; ALZHEIMERS-DISEASE; RISK; DISORDERS; PHARMACOGENETICS; ASSOCIATION; DISCLOSURE; BEHAVIOR; REVEAL AB Purpose of reviewThis review outlines the positive and negative aspects of DNA testing and provides an account of the issues particularly relevant to schizophrenia.Recent findingsModern technology has changed the field of medicine so rapidly that patients and their families have become much more independent in their healthcare decisions than in the previous decade. Simply by finding information on the Internet, they gain knowledge about disease diagnosis, treatment options and their side-effects. No medical field likely has been more affected and more controversial than that of genetics. It is now possible to sequence the individual human genome and detect single nucleotide variations, microdeletions and duplications within it. Commercial companies have sprung up in a similar manner to the software or electronic industries and have begun to market direct-to-consumer DNA testing. Much of this may be performed to satisfy curiosity about one's ancestry; but commercially available results that appear incidentally can also be distributed to the consumer.SummaryEthicists, genetics researchers, clinicians and government agencies are currently in discussion about concerns raised about commercially available DNA testing, while at the same time recognizing its value in some instances to be able to predict very serious disabilities. C1 [DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, Boston, MA USA. RP DeLisi, LE (reprint author), VA Boston Healthcare Syst, 940 Belmont Ave, Brockton, MA 02301 USA. EM Lynn_DeLisi@hms.harvard.edu NR 28 TC 1 Z9 1 U1 3 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 EI 1473-6578 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2014 VL 27 IS 3 BP 191 EP 196 DI 10.1097/YCO.0000000000000060 PG 6 WC Psychiatry SC Psychiatry GA AG3WB UT WOS:000335349500005 PM 24662960 ER PT J AU Chen, JW Galloway, JL AF Chen, Jessica W. Galloway, Jenna L. TI The development of zebrafish tendon and ligament progenitors SO DEVELOPMENT LA English DT Article DE Tendon; Craniofacial; Zebrafish ID MYOGENIC REGULATORY FACTORS; DANIO-RERIO OSTARIOPHYSI; PREMAXILLARY PROTRUSION; FUNCTIONAL-MORPHOLOGY; MUSCLE-CONTRACTION; COLLAGEN GENE; LIMB TENDONS; CELL FATE; EXPRESSION; SCLERAXIS AB Despite the importance of tendons and ligaments for transmitting movement and providing stability to the musculoskeletal system, their development is considerably less well understood than that of the tissues they serve to connect. Zebrafish have been widely used to address questions in muscle and skeletal development, yet few studies describe their tendon and ligament tissues. We have analyzed in zebrafish the expression of several genes known to be enriched in mammalian tendons and ligaments, including scleraxis (scx), collagen 1a2 (col1a2) and tenomodulin (tnmd), or in the tendon-like myosepta of the zebrafish (xirp2a). Co-expression studies with muscle and cartilage markers demonstrate the presence of scxa, col1a2 and tnmd at sites between the developing muscle and cartilage, and xirp2a at the myotendinous junctions. We determined that the zebrafish craniofacial tendon and ligament progenitors are neural crest derived, as in mammals. Cranial and fin tendon progenitors can be induced in the absence of differentiated muscle or cartilage, although neighboring muscle and cartilage are required for tendon cell maintenance and organization, respectively. By contrast, myoseptal scxa expression requires muscle for its initiation. Together, these data suggest a conserved role for muscle in tendon development. Based on the similarities in gene expression, morphology, collagen ultrastructural arrangement and developmental regulation with that of mammalian tendons, we conclude that the zebrafish tendon populations are homologous to their force-transmitting counterparts in higher vertebrates. Within this context, the zebrafish model can be used to provide new avenues for studying tendon biology in a vertebrate genetic system. C1 [Chen, Jessica W.; Galloway, Jenna L.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Chen, Jessica W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Galloway, JL (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM jenna_galloway@hms.harvard.edu FU National Institiutes of Health (NIH) [PO1 DK056246]; National Science Foundation (NSF); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH [K99/R00HD069533]; Harvard Stem Cell Institute (HSCI) FX J.W.C. is supported by the National Institiutes of Health (NIH) [PO1 DK056246] and by a National Science Foundation (NSF) Predoctoral Fellowship. J.L.G. is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH [K99/R00HD069533] and the Harvard Stem Cell Institute (HSCI). Deposited in PMC for release after 12 months. NR 75 TC 15 Z9 15 U1 1 U2 11 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD MAY 1 PY 2014 VL 141 IS 10 BP 2035 EP 2045 DI 10.1242/dev.104067 PG 11 WC Developmental Biology SC Developmental Biology GA AH4VH UT WOS:000336126400006 PM 24803652 ER PT J AU Cho, NL Moalem, J Chen, L Lubitz, CC Moore, FD Ruan, DT AF Cho, Nancy L. Moalem, Jacob Chen, Lily Lubitz, Carrie C. Moore, Francis D., Jr. Ruan, Daniel T. TI SURGEONS AND PATIENTS DISAGREE ON THE POTENTIAL CONSEQUENCES OF HYPOPARATHYROIDISM SO ENDOCRINE PRACTICE LA English DT Article ID INFORMED-CONSENT; THYROID-SURGERY; QUESTIONNAIRE AB Objective: To test the hypothesis that surgeons and their patients underestimate the potential negative impact that permanent hypoparathyroidism has on quality of life (QOL). Methods: We used a modified SF-36 assessment tool to compare the perceptions of patients with permanent hypoparathyroidism to the perceptions of control subjects who were given a standardized preoperative statement about the complications of hypoparathyroidism. We also elicited the perceptions of endocrine surgeons regarding the QOL impacts of hypoparathyroidism using a subset of questions from the modified SF-36. Results: A total of 340 postsurgical patients with permanent hypoparathyroidism, 200 controls, and 102 surgeons participated in the study. Both surgeons and controls underestimated the negative impact of hypoparathyroidism on QOL when compared to patients living with permanent hypoparathyroidism. Forty-seven percent of hypoparathyroid patients believed that their health was "much worse" than before surgery, compared with 16% of surgeons (P<.001) and 7% of controls (P<.001). Postoperative hypoparathyroid patients also reported far more negative effects on QOL, from interference with social activities, paresthesias, muscle cramping, and medications than were anticipated by surgeons or controls (P<.05 for all comparisons). In each of the 8 dimensions of QOL, including physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health, hypoparathyroid patients reported a significantly lower mean score compared to the control group (P<.001 for all comparisons). Conclusion: The impact of postoperative hypoparathyroidism on patient QOL is consistently and significantly underestimated by surgeons and subjects receiving surgical consultation. C1 [Cho, Nancy L.; Chen, Lily; Moore, Francis D., Jr.; Ruan, Daniel T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Moalem, Jacob] Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA. [Lubitz, Carrie C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cho, NL (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM nlcho@partners.org NR 14 TC 7 Z9 7 U1 2 U2 5 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAY PY 2014 VL 20 IS 5 BP 427 EP 446 DI 10.4158/EP13321.OR PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AH3SL UT WOS:000336045500010 PM 24325999 ER PT J AU Pace-Schott, EF Tracy, LE Rubin, Z Mollica, AG Ellenbogen, JM Bianchi, MT Milad, MR Pitman, RK Orr, SP AF Pace-Schott, Edward F. Tracy, Lauren E. Rubin, Zoe Mollica, Adrian G. Ellenbogen, Jeffrey M. Bianchi, Matt T. Milad, Mohammed R. Pitman, Roger K. Orr, Scott P. TI Interactions of time of day and sleep with between-session habituation and extinction memory in young adult males SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Sleep; Habituation; Extinction; Startle; Orienting ID FEAR EXTINCTION; EXPOSURE THERAPY; EMOTIONAL REACTIVITY; PREFRONTAL CORTEX; AMYGDALA ACTIVITY; CONDITIONED FEAR; FEMALE RATS; BEHAVIOR; HUMANS; PTSD AB Within-session habituation and extinction learning co-occur as do subsequent consolidation of habituation (i.e., between-session habituation) and extinction memory. We sought to determine whether, as we predicted: (1) between-session habituation is greater across a night of sleep versus a day awake; (2) time-of-day accounts for differences; (3) between-session habituation predicts consolidation of extinction memory; (4) sleep predicts between-session habituation and/or extinction memory. Participants (N = 28) completed 4-5 sessions alternating between mornings and evenings over 3 successive days (2 nights) with session 1 in either the morning (N = 13) or evening (N = 15). Twelve participants underwent laboratory polysomnography. During 4 sessions, participants completed a loud-tone habituation protocol, while skin conductance response (SCR), blink startle electromyography (EMG), heart-rate acceleration and heart-rate deceleration (HRD) were recorded. For sessions 1 and 2, between-session habituation of EMG, SCR and HRD was greater across sleep. SCR and HRD were generally lower in the morning. Between-session habituation of SCR for sessions 1 and 2 was positively related to intervening (first night) slow wave sleep. In the evening before night 2, participants also underwent fear conditioning and extinction learning phases of a second protocol. Extinction recall was tested the following morning. Extinction recall was predicted only by between-session habituation of SCR across the same night (second night) and by intervening REM. We conclude that: (1) sleep augments between-session habituation, as does morning testing; (2) extinction recall is predicted by concurrent between-session habituation; and (3) both phenomena may be influenced by sleep. C1 [Pace-Schott, Edward F.; Tracy, Lauren E.; Rubin, Zoe; Mollica, Adrian G.; Milad, Mohammed R.; Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Pace-Schott, Edward F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Ellenbogen, Jeffrey M.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Bianchi, Matt T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pace-Schott, EF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CNY 149 13th St Room 2510, Charlestown, MA 02129 USA. EM epace-schott@mgh.harvard.edu FU NIMH NIH HHS [R21 MH090357] NR 56 TC 5 Z9 5 U1 4 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 EI 1432-1106 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2014 VL 232 IS 5 SI SI BP 1443 EP 1458 DI 10.1007/s00221-014-3829-9 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AH0OH UT WOS:000335819100005 PM 24481663 ER PT J AU Connors, EC Chrastil, ER Sanchez, J Merabet, LB AF Connors, Erin C. Chrastil, Elizabeth R. Sanchez, Jaime Merabet, Lotfi B. TI Virtual environments for the transfer of navigation skills in the blind: a comparison of directed instruction vs. video game based learning approaches SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE early blind; late blind; navigation; spatial cognition; games for learning; videogames; virtual; environment; near transfer of learning ID SPATIAL KNOWLEDGE; VISUAL EXPERIENCE; INDIVIDUAL-DIFFERENCES; GENDER-DIFFERENCES; COGNITIVE MAPS; PEOPLE; REALITY; ROUTE; REPRESENTATION; MEMORY AB For profoundly blind individuals, navigating in an unfamiliar building can represent a significant challenge. We investigated the use of an audio-based, virtual environment called Audio-based Environment Simulator (AbES) that can be explored for the purposes of learning the layout of an unfamiliar, complex indoor environment. Furthermore, we compared two modes of interaction with AbES. In one group, blind participants implicitly learned the layout of a target environment while playing an exploratory, goal-directed video game. By comparison, a second group was explicitly taught the same layout following a standard route and instructions provided by a sighted facilitator. As a control, a third group interacted with AbES while playing an exploratory, goal-directed video game however, the explored environment did not correspond to the target layout. Following interaction with AbES, a series of route navigation tasks were carried out in the virtual and physical building represented in the training environment to assess the transfer of acquired spatial information. We found that participants from both modes of interaction were able to transfer the spatial knowledge gained as indexed by their successful route navigation performance. This transfer was not apparent in the control participants. Most notably, the game-based learning strategy was also associated with enhanced performance when participants were required to find alternate routes and short cuts within the target building suggesting that a ludic-based training approach may provide for a more flexible mental representation of the environment. Furthermore, outcome comparisons between early and late blind individuals suggested that greater prior visual experience did not have a significant effect on overall navigation performance following training. Finally, performance did not appear to be associated with other factors of interest such as age, gender, and verbal memory recall. We conclude that the highly interactive and immersive exploration of the virtual environment greatly engages a blind user to develop skills akin to positive near transfer of learning. Learning through a game play strategy appears to confer certain behavioral advantages with respect to how spatial information is acquired and ultimately manipulated for navigation. C1 [Connors, Erin C.; Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Lab Visual Neuroplast, Boston, MA 02114 USA. [Chrastil, Elizabeth R.] Boston Univ, Dept Psychol, Ctr Memory & Brain, Boston, MA 02215 USA. [Sanchez, Jaime] Univ Chile, Dept Comp Sci, Ctr Adv Res Educ, Santiago, Chile. RP Merabet, LB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 20 Staniford St, Boston, MA 02114 USA. EM lotfi_merabet@meei.harvard.edu OI Chrastil, Elizabeth/0000-0003-2544-0152 FU NIH/NEI RO1 [EY019924]; Chilean National Fund of Science and Technology, [1120330] FX This work was supported by an NIH/NEI RO1 GRANT EY019924 (Lotfi B. Merabet) and also funded by the Chilean National Fund of Science and Technology, Fondecyt #1120330 and Project CIE05 Program Center Education PBCT-Conicyt (Jaime Sanchez). The authors would like to thank the research participants, as well as Rabih Dow, Padma Rajagopal and the staff of the Carroll Center for the Blind (Newton MA, USA) for their support in carrying out this research. NR 68 TC 2 Z9 2 U1 4 U2 38 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAY 1 PY 2014 VL 8 AR 223 DI 10.3389/fnhum.2014.00223 PG 13 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AH4JY UT WOS:000336094400001 PM 24822044 ER PT J AU Lacerte, G Langlois, MF Doyon, M Brown, C Carpentier, AC Hivert, MF AF Lacerte, G. Langlois, M. -F. Doyon, M. Brown, C. Carpentier, A. C. Hivert, M. -F. TI Differential Impact of Changes in Adiposity Distribution on Insulin Resistance and Adiponectin Variations Over 4 Years in Normal Weight Young Adults SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE weight gain; waist circumference; percent body fat; adiponectin; insulin resistance; young adults ID FAT DISTRIBUTION; RISK-FACTORS; FITNESS TEST; GLUCOSE; OBESITY; CARDIA; GAIN; ASSOCIATIONS; TISSUE; MEN AB The aim of the study was to evaluate the influence of weight gain and changes in adiposity distribution on insulin resistance and circulating adiponectin variations over 4 years in free-living normal weight young adults. In this prospective observational cohort (n=42 women, 18 men), anthropometric measurements and blood samples were collected in the fasting state at baseline and at 4 years. Insulin resistance was estimated using the homeostatic model assessment (HOMA-IR). Circulating adiponectin levels were determined by radioimmunoassay. To investigate increase in adiposity more specifically, subsidiary analyses were performed in a subgroup of individuals (n=31) who gained adiposity over the course of the 4-year follow-up (defined as gain >1% in percent body fat). Regression analyses were performed to adjust for sex, age, parental education, lifestyle, and fitness levels. At baseline, the participants were young adults (age=20.0 years old) in the normal weight range [body mass index (BMI)=22.7kg/m(2) (IQR=21.1-24.4)]. Median change in body fat percentage was +1.4% (IQR=-0.3-3.4; p=0.01) and in waist circumference was +1.2cm (IQR=-2.6-5.3; p=0.05). In the subgroup of individuals who gained more than 1% body fat, increase in HOMA-IR was associated with an increase in BMI (r=0.44; p=0.01; p<0.01 in fully adjusted model), while decrease in adiponectin levels was associated with an increase in waist circumference (r=-0.38; p=0.03) but this was no longer significant after adjustment for sex and other potential confounders (p=0.14). In a population of young adults, small variations in adiposity within the normal weight range were associated with increase in insulin resistance. C1 [Lacerte, G.; Langlois, M. -F.; Doyon, M.; Brown, C.; Carpentier, A. C.; Hivert, M. -F.] CHU Sherbrooke, Ctr Rech Clin Etienne LeBel, Sherbrooke, PQ J1H 5N4, Canada. [Langlois, M. -F.; Carpentier, A. C.; Hivert, M. -F.] Univ Sherbrooke, Div Endocrinol, Dept Med, Sherbrooke, PQ J1H 5N4, Canada. [Hivert, M. -F.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Univ Sherbrooke, Fac Med, Dept Med, 3001,12th Ave North, Sherbrooke, PQ J1H 5N4, Canada. EM marie-france.hivert@usherbrooke.ca FU Canadian Diabetes Association (CDA); Danone Institute; Centre de recherche clinique Etienne-Le Bel is a Fonds de la recherche en sante du Quebec (FRSQ); FRSQ; CDA; CIHR-GSK Chair in Diabetes FX This work was supported by grants from the Canadian Diabetes Association (CDA) and the Danone Institute. The Centre de recherche clinique Etienne-Le Bel is a Fonds de la recherche en sante du Quebec (FRSQ)-funded research center. MFH received career awards from the FRSQ (Research Scholar Award, junior 1 level) and from the CDA (Clinical Scientist). MFL is recipient of a career award from the FRSQ (National researcher). ACC is the recipient of the CIHR-GSK Chair in Diabetes and is supported by a career award from the FRSQ (Research Scholar Award, Senior level). NR 23 TC 3 Z9 3 U1 0 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD MAY PY 2014 VL 46 IS 5 BP 354 EP 359 DI 10.1055/s-0033-1363224 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG6SE UT WOS:000335547900009 PM 24446154 ER PT J AU Chong, TA Strazzula, L Hoang, MP Arakaki, R Kroshinsky, D AF Chong, Tracie Ann Strazzula, Lauren Hoang, Mai P. Arakaki, Ryan Kroshinsky, Daniela TI Giant Primary Melanoma With No Apparent Metastases: A Report of 2 Cases SO JAMA DERMATOLOGY LA English DT Letter C1 [Chong, Tracie Ann] Univ Hawaii, John A Burns Sch Med, Sch Med, Honolulu, HI 96822 USA. [Strazzula, Lauren; Hoang, Mai P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoang, Mai P.; Arakaki, Ryan; Kroshinsky, Daniela] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,Ste 200, Boston, MA 02114 USA. EM dkroshinsky@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAY PY 2014 VL 150 IS 5 BP 574 EP 575 DI 10.1001/jamadermatol.2013.6892 PG 2 WC Dermatology SC Dermatology GA AH2NH UT WOS:000335957700023 PM 24477240 ER PT J AU Frigerio, A Hadlock, TA Murray, EH Heaton, JT AF Frigerio, Alice Hadlock, Tessa A. Murray, Elizabeth H. Heaton, James T. TI Infrared-Based Blink-Detecting Glasses for Facial Pacing Toward a Bionic Blink SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID SYSTEM; STIMULATION; ELECTROMYOGRAPHY; DROWSINESS; MOVEMENTS AB IMPORTANCE Facial paralysis remains one of the most challenging conditions to effectively manage, often causing life-altering deficits in both function and appearance. Facial rehabilitation via pacing and robotic technology has great yet unmet potential. A critical first step toward reanimating symmetrical facial movement in cases of unilateral paralysis is the detection of healthy movement to use as a trigger for stimulated movement. OBJECTIVE To test a blink detection system that can be attached to standard eyeglasses and used as part of a closed-loop facial pacing system. DESIGN, SETTING, AND PARTICIPANTS Standard safety glasses were equipped with an infrared (IR) emitter-detector unit, oriented horizontally across the palpebral fissure, creating a monitored IR beam that became interrupted when the eyelids closed, and were tested in 24 healthy volunteers from a tertiary care facial nerve center community. MAIN OUTCOMES AND MEASURES Video-quantified blinking was compared with both IR sensor signal magnitude and rate of change in healthy participants with their gaze in repose, while they shifted their gaze from central to far-peripheral positions, and during the production of particular facial expressions. RESULTS Blink detection based on signal magnitude achieved 100% sensitivity in forward gaze but generated false detections on downward gaze. Calculations of peak rate of signal change (first derivative) typically distinguished blinks from gaze-related eyelid movements. During forward gaze, 87% of detected blink events were true positives, 11% were false positives, and 2% were false negatives. Of the 11% false positives, 6% were associated with partial eyelid closures. During gaze changes, false blink detection occurred 6% of the time during lateral eye movements, 10% of the time during upward movements, 47% of the time during downward movements, and 6% of the time for movements from an upward or downward gaze back to the primary gaze. Facial expressions disrupted sensor output if they caused substantial squinting or shifted the glasses. CONCLUSIONS AND RELEVANCE Our blink detection system provides a reliable, noninvasive indication of eyelid closure using an invisible light beam passing in front of the eye. Future versions will aim to mitigate detection errors by using multiple IR emitter-detector units mounted on glasses, and alternative frame designs may reduce shifting of the sensors relative to the eye during facial movements. C1 [Frigerio, Alice] Univ Milan, Dept Pathophysiol & Transplantat, Human Physiol Sect, Milan, Italy. [Frigerio, Alice; Hadlock, Tessa A.] Harvard Univ, Sch Med,Carolyn & Peter Lynch Ctr Laser & Reconst, Massachusetts Eye & Ear Infirm,Facial Nerve Ctr, Dept Otol & Laryngol,Div Facial Plast & Reconstru, Boston, MA 02114 USA. [Murray, Elizabeth H.; Heaton, James T.] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA USA. [Heaton, James T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Facial Nerve Ctr, Dept Otol & Laryngol,Div Facial Plast & Reconstru, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu OI Frigerio, Alice/0000-0001-9202-9553 FU NINDS NIH HHS [R01 NS071067] NR 21 TC 4 Z9 4 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAY-JUN PY 2014 VL 16 IS 3 BP 211 EP 218 DI 10.1001/jamafacial.2014.1 PG 8 WC Surgery SC Surgery GA AH2PE UT WOS:000335962600010 PM 24699708 ER PT J AU Kahle, KT Khanna, A Clapham, DE Woolf, CJ AF Kahle, Kristopher T. Khanna, Arjun Clapham, David E. Woolf, Clifford J. TI Therapeutic Restoration of Spinal Inhibition via Druggable Enhancement of Potassium-Chloride Cotransporter KCC2-Mediated Chloride Extrusion in Peripheral Neuropathic Pain SO JAMA NEUROLOGY LA English DT Article ID DORSAL-HORN; GABAERGIC INHIBITION; ANION GRADIENT; NERVE INJURY; CORD; NEURONS; KCC2; HYPERSENSITIVITY; DISINHIBITION; HOMEOSTASIS AB Peripheral neuropathic pain, typified by the development of spontaneous pain or pain hypersensitivity following injury to the peripheral nervous system, is common, greatly impairs quality of life, and is inadequately treated with available drugs. Maladaptive changes in chloride homeostasis due to a decrease in the functional expression of the potassium-chloride cotransporter KCC2 in spinal cord dorsal horn neurons are a major contributor to the central disinhibition of gamma-aminobutyric acid type A receptor- and glycine receptor- mediated signaling that characterizes neuropathic pain. A compelling novel analgesic strategy is to restore spinal ionotropic inhibition by enhancing KCC2-mediated chloride extrusion. We review the data on which this theory of alternative analgesia is based, discuss recent high-throughput screens that have searched for small-molecule activators of KCC2, and propose other strategies of KCC2 activation based on recent developments in the basic understanding of KCC2's functional regulation. Exploiting the chloride-dependent functional plasticity of the gamma-aminobutyric acid and glycinergic system by targeting KCC2 may be a tenable method of restoring ionotropic inhibition not only in neuropathic pain but also in other "hyperexcitable" diseases of the nervous system such as seizures and spasticity. C1 [Kahle, Kristopher T.; Khanna, Arjun] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.; Khanna, Arjun] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02124 USA. [Kahle, Kristopher T.; Clapham, David E.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02124 USA. [Kahle, Kristopher T.; Clapham, David E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02124 USA. [Kahle, Kristopher T.; Clapham, David E.] Manton Ctr Orphan Dis Res, Boston, MA USA. [Woolf, Clifford J.] Harvard Univ, Boston Childrens Hosp, Sch Med, FM Kirby Neurobiol Ctr, Boston, MA 02124 USA. [Woolf, Clifford J.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02124 USA. RP Kahle, KT (reprint author), Harvard Univ, Manton Ctr Orphan Dis Res, Sch Med, Dept Neurosurg,Massachusetts Gen Hosp,Dept Neurob, 300 Longwood Ave,Enders Bldg,Room 1309, Boston, MA 02124 USA. EM kkahle@enders.tch.harvard.edu FU National Institutes of Health; Howard Hughes Medical Institute; Manton Center for Orphan Disease Research FX This work was supported by the National Institutes of Health (Drs Kahle, Clapham, and Woolf), the Howard Hughes Medical Institute (Dr Clapham), and the Manton Center for Orphan Disease Research (Drs Kahle and Clapham). NR 24 TC 11 Z9 11 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAY PY 2014 VL 71 IS 5 BP 640 EP 645 DI 10.1001/jamaneurol.2014.21 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AH2MX UT WOS:000335956700019 PM 24615367 ER PT J AU Friedman, MJ AF Friedman, Matthew J. TI Suicide Risk Among Soldiers Early Findings From Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) SO JAMA PSYCHIATRY LA English DT Editorial Material ID US MILITARY PERSONNEL; MENTAL-HEALTH C1 [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, Washington, DC USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA. RP Friedman, MJ (reprint author), VA Med Ctr, US Natl Ctr PTSD, Geisel Sch Med Dartmouth, Dept Pharmacol & Psychiat, 215 N Main St, White River Jct, VT 05009 USA. EM matthew.j.friedman@dartmouth.edu NR 10 TC 8 Z9 8 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2014 VL 71 IS 5 BP 487 EP 489 DI 10.1001/jamapsychiatry.2014.24 PG 3 WC Psychiatry SC Psychiatry GA AH2JP UT WOS:000335947600003 PM 24590002 ER PT J AU Byers, AL Covinsky, KE Neylan, TC Yaffe, K AF Byers, Amy L. Covinsky, Kenneth E. Neylan, Thomas C. Yaffe, Kristine TI Chronicity of Posttraumatic Stress Disorder and Risk of Disability in Older Persons SO JAMA PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; WORLD-HEALTH-ORGANIZATION; QUALITY-OF-LIFE; FUNCTIONAL IMPAIRMENT; PHYSICAL-DISABILITY; PRIMARY-CARE; GERIATRIC DEPRESSION; FUTURE-RESEARCH; SYMPTOMS; DECLINE AB IMPORTANCE Little is known about the association between posttraumatic stress disorder (PTSD) and disability into later life. Most studies of late-life psychiatric disorders and function have focused on depression and generalized anxiety disorder. OBJECTIVES To determine the association between PTSD and disability among older adults and investigate if association differs by chronicity of PTSD. DESIGN, SETTING, AND PARTICIPANTS In total, 3287 participants 55 years and older (mean [SD] age, 66.0 [8.7] years, 60.1% women) involved in the Collaborative Psychiatric Epidemiology Surveys (2001-2003), including 3 aggregated, nationally representative studies (National Comorbidity Survey Replication, National Survey of American Life, and National Latino and Asian American Study). Analyses used weights and complex design-corrected statistical tests to infer generalizability to the US population. MAIN OUTCOMES AND MEASURES Disability defined by 5 domains (out of role, self-care, mobility, cognition, and social) using theWorld Health Organization Disability Assessment Schedule. RESULTS Of the 3.7% older adults who had a history of PTSD defined by DSM-IV criteria, 1.8% had persistent PTSD into later life (age of onset < 55 years as well as a recent diagnosis). Frequency of any disability was 79.7% for persistent PTSD, 69.6% for pre-late life (age of onset < 55 years and age at last diagnosis < 55 years), and 36.9% for no PTSD (P <.001). In logistic regression analyses, adjusting for demographics, smoking, individual medical conditions, depression, generalized anxiety disorder, and substance use disorders, respondents with persistent PTSD were 3 times more likely to have any disability than were respondents with no PTSD (odds ratio, 3.18; 95% CI, 1.32-7.64). Global disability results were nonsignificant for pre-late life relative to no PTSD (odds ratio, 1.99; 95% CI, 0.97-4.08). CONCLUSIONS AND RELEVANCE Disability in older Americans is strongly associated with PTSD, particularly PTSD that persists into later life. These findings suggest that monitoring and treatment of PTSD are important over the long term. C1 [Byers, Amy L.; Neylan, Thomas C.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Byers, Amy L.; Covinsky, Kenneth E.; Neylan, Thomas C.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Byers, AL (reprint author), San Francisco VA Med Ctr, Dept Psychiat, 4150 Clement St,Mail Code 116H, San Francisco, CA 94121 USA. EM amy.byers@ucsf.edu FU Department of Defense [W81XWH-11-2-0189]; National Institute of Mental Health [U01-MH60220, U01-MH57716, U01-MH062209, U01-MH62207]; National Institute of Drug Abuse [R01-DA12058-05]; Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044708]; National Institutes of Health; University of Michigan, Ann Arbor FX This study was supported by Department of Defense grant W81XWH-11-2-0189, which was administered by the Northern California Institute for Research and Education and with resources of the San Francisco Veterans Affairs Medical Center (Dr Byers), and in part by a K24 Midcareer Investigator Award (AG031155) from the National Institute on Aging (Dr Yaffe). The National Comorbidity Survey Replication was supported by the National Institute of Mental Health (U01-MH60220), with supplemental support from the National Institute of Drug Abuse (R01-DA12058-05), the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation (044708), and the JohnW. Alden Trust. The National Survey of American Life was supported by the National Institute of Mental Health (U01-MH57716), with supplemental support from the Office of Behavioral and Social Sciences Research at the National Institutes of Health and the University of Michigan, Ann Arbor. The National Latino and Asian American Study was supported by the National Institute of Mental Health (U01-MH062209 and U01-MH62207), with supplemental support from the Office of Behavioral and Social Sciences Research at the National Institutes of Health, the Substance Abuse and Mental Health Services Agency, and the Latino Research Program Project (P01-MH059876). NR 40 TC 11 Z9 11 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2014 VL 71 IS 5 BP 540 EP 546 DI 10.1001/jamapsychiatry.2014.5 PG 7 WC Psychiatry SC Psychiatry GA AH2JP UT WOS:000335947600011 PM 24647756 ER PT J AU Yeghiazarians, Y Honbo, N Imhof, I Woods, B Aguilera, V Ye, JQ Boyle, AJ Karliner, JS AF Yeghiazarians, Yerem Honbo, Norman Imhof, Isabella Woods, Brandon Aguilera, Vanessa Ye, Jianqin Boyle, Andrew J. Karliner, Joel S. TI IL-15: A Novel Prosurvival Signaling Pathway in Cardiomyocytes SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE stem cell; IL-15; survival; cardiomyocyte ID SPHINGOSINE 1-PHOSPHATE; ISCHEMIC-HEART; STEM-CELLS; FUNCTIONAL IMPROVEMENT; INTERLEUKIN-15; APOPTOSIS; HYPOXIA; ASSOCIATION; FIBROBLASTS; MYOCARDIUM AB Cardiovascular disease is the leading cause of death in Western countries. A major limitation of current treatments is the inability to efficiently repair or replace dead myocardium. Recently, stem cell-based therapies have been explored as an avenue to circumvent current therapeutic limitations. Overall, these therapies seem to result in small improvements in the contractile function of the heart. The exact mechanism(s) of action that underlie these improvements remain unknown, and it is believed that paracrine effects play a significant role. Previously, we had reported that an extract derived from bone marrow cells, in the absence of any live cell, contained cardioprotective soluble factors. In this study, we identify IL-15 as a putative cardioprotectant within the bone marrow cells paracrine profile. Using an in vitro culture system, we assessed the ability of IL-15 to protect cardiomyocytes under hypoxic conditions. For the first time, we have identified IL-15 receptors on the surface of cardiomyocytes and delineated the signaling system by which hypoxic cardiomyocytes may be protected from cellular death and rescued from oxidative stress with IL-15 treatment. C1 [Yeghiazarians, Yerem; Woods, Brandon; Aguilera, Vanessa; Ye, Jianqin; Boyle, Andrew J.; Karliner, Joel S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Yeghiazarians, Yerem; Boyle, Andrew J.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Yeghiazarians, Yerem; Karliner, Joel S.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Honbo, Norman; Imhof, Isabella; Karliner, Joel S.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Yeghiazarians, Y (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Box 0103, San Francisco, CA 94143 USA. EM yeghiaza@medicine.ucsf.edu FU UCSF Translational Cardiac Stem Cell Program; Leone-Perkins Foundation; Torian Foundation; Vadasz Foundation; Foundation for Cardiac Research; Chatterjee Center for Cardiac Research; [HL R01 090606] FX Supported by the UCSF Translational Cardiac Stem Cell Program, the Leone-Perkins Foundation, the Torian Foundation and the Vadasz Foundation (all to Y.Y.), and by HL R01 090606, the Foundation for Cardiac Research, and the Chatterjee Center for Cardiac Research (all to J.S.K.). NR 27 TC 3 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAY PY 2014 VL 63 IS 5 BP 406 EP 411 DI 10.1097/FJC.0000000000000061 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA AH2KZ UT WOS:000335951500003 PM 24805144 ER PT J AU Baker, KM Zavotsky, KE Wolf, LA Carman, MJ Clark, PR Langkeit, K Lenehan, G Moon, M AF Baker, Kathy M. Zavotsky, Kathleen E. Wolf, Lisa A. Carman, Margaret J. Clark, Paul R. Langkeit, Kevin Lenehan, Gail Moon, Michael TI STATISTICS FOR EMERGENCY NURSES SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Baker, Kathy M.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Zavotsky, Kathleen E.] Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA. [Wolf, Lisa A.] Emergency Nurses Assoc, Inst Emergency Nursing Res, Des Plaines, IL 60016 USA. [Carman, Margaret J.] Duke Univ, Sch Nursing, Durham, NC USA. [Clark, Paul R.] Norton Healthcare Inst Nursing, Louisville, KY USA. [Langkeit, Kevin] Intermt Med Ctr, Emergency Dept, Bountiful, UT USA. [Lenehan, Gail] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moon, Michael] Univ Incarnate Word, Sch Nursing, San Antonio, TX USA. RP Wolf, LA (reprint author), Emergency Nurses Assoc, Inst Emergency Nursing Res, 915 Lee St, Des Plaines, IL 60016 USA. EM lwolf@ena.org NR 3 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 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAY PY 2014 VL 40 IS 3 BP 286 EP 288 DI 10.1016/j.jen.2014.02.005 PG 3 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA AG6XE UT WOS:000335561500026 PM 24810509 ER PT J AU Scarparo, RK Dondoni, L Boettcher, DE Grecca, FS Figueiredo, JAP Kantarci, A Van Dyke, TE Batista, EL AF Scarparo, Roberta Kochenborger Dondoni, Lenara Boettcher, Daiana Elisabeth Grecca, Fabiana Soares Figueiredo, Jose Antonio P. Kantarci, Alpdogan Van Dyke, Thomas E. Batista, Eraldo Luiz, Jr. TI Intracanal Delivery of Resolvin E1 Controls Inflammation in Necrotic Immature Rat Teeth SO JOURNAL OF ENDODONTICS LA English DT Article DE Immature teeth; inflammation resolution; Resolvin E1; root development ID PERMANENT TEETH; STEM-CELLS; APICAL PERIODONTITIS; PULP NECROSIS; CALCIUM HYDROXIDE; REVASCULARIZATION; MEDICATION; MEDIATORS; MODEL; PASTE AB Introduction: Pulp necrosis in immature teeth and the resulting periodontal apical inflammation negatively affect root formation. Resolvin E1 (RvE1) is a lipidderived endogenous pro-resolution molecule that controls inflammation. The aim of this investigation was to evaluate the impact of RvE1 applied as an intracanal medication on root formation in nonvital immature teeth. Methods: To arrest root development, pulpectomy was performed in the lower first molars of 4week-old Wistar rats. After 3 weeks, irrigation with 2.5% sodium hypochlorite and 0.9% sterile saline was performed, and either a triple antibiotic paste (TAP) or RvE1 in saline was applied into the root canals. In the control group, access openings drilled into molars were left exposed to the oral environment. Root development and periapical repair were evaluated radiographically and histologically at 3 and 6 weeks after treatment. Results: RvE1 reduced periapical lesion size compared with the control at 3 weeks, which was similar to TAP. Inflammatory response in the RvE1 treated group was markedly reduced compared with both TAP and control specimens. At 6 weeks, root development was observed in both groups, but RvE1 treatment produced less cellularity with more regular calcified tissue deposition. Conclusions: RvE1 and TAP had a positive impact on reducing inflammation and promoting root formation. RvE1 was more effective in reducing inflammation at earlier stages. RvE1 has potential to be used as root canal dressing to control inflammation in endodontically compromised teeth before complete root formation. Stability of RvE1 within the root canal and its delivery are issues to be addressed before its clinical use. C1 [Scarparo, Roberta Kochenborger; Dondoni, Lenara; Figueiredo, Jose Antonio P.] Pontificia Univ Catolica Rio Grande do Sul PUCRS, Porto Alegre, RS, Brazil. [Boettcher, Daiana Elisabeth; Grecca, Fabiana Soares] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol & Translat Biol Res, Cambridge, MA USA. [Batista, Eraldo Luiz, Jr.] Univ Manitoba, Div Periodontol, Dept Diagnost & Surg Sci, Fac Dent, Winnipeg, MB, Canada. [Batista, Eraldo Luiz, Jr.] Univ Manitoba, Fac Dent, Dept Oral Biol, Winnipeg, MB, Canada. RP Batista, EL (reprint author), Univ Manitoba, Fac Dent, D3429-790 Bannatyne Ave, Winnipeg, MB R3E 0W2, Canada. EM eraldo.batistajunior@umanitoba.ca RI Figueiredo, Jose Antonio/I-4805-2012 OI Figueiredo, Jose Antonio/0000-0002-8876-5993 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Brazil FX This study was supported by grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Brazil. NR 28 TC 0 Z9 1 U1 5 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 EI 1878-3554 J9 J ENDODONT JI J. Endod. PD MAY PY 2014 VL 40 IS 5 BP 678 EP 682 DI 10.1016/j.joen.2013.12.037 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AH1IG UT WOS:000335873200014 PM 24767563 ER PT J AU Tritos, NA Biller, BMK AF Tritos, Nicholas A. Biller, Beverly M. K. TI Medical management of Cushing's disease SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Cushing's syndrome; Cushing's disease; Pituitary adenoma; Medical therapy ID TRANSSPHENOIDAL SURGERY; LAPAROSCOPIC ADRENALECTOMY; DOPAMINE AGONISTS; SINGLE-CENTER; THERAPY; KETOCONAZOLE; PASIREOTIDE; MIFEPRISTONE; CABERGOLINE; METYRAPONE AB Cushing's disease (CD), caused by excess adrenocorticotropin secretion from tumorous pituitary corticotrophs, is associated with substantial morbidity and mortality. The primary, definitive therapy for patients with CD is selective pituitary adenomectomy, generally performed via a transsphenoidal approach. Medical therapy has an important adjunctive role in the management of patients with CD, including preoperative patient preparation in patients with severe disease, and temporizing management of hypercortisolism while awaiting the effects of radiation therapy to occur in patients who are not in remission postoperatively. Medical therapy can also be used in patients with hypercortisolism of unclear origin or in the few patients who decline or are unfit for surgery. Available medical options for patients with CD include centrally acting agents (cabergoline and pasireotide), steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane and etomidate) and a glucocorticoid receptor antagonist (mifepristone). Pasireotide and mifepristone have been recently granted regulatory approval in some countries for use in patients with CD, whereas other medications are used "off label" in this patient population. As clinical trials using comparator agents have not been reported, the choice between different medications is based on patient characteristics and preference. Despite impressive advances in pharmacotherapy for patients with CD, much remains to be done. The long term efficacy and safety of medical therapies for hypercortisolism need to be evaluated and the role of combination therapy must be further characterized. As the pathogenesis of CD becomes better understood at the molecular level, it is likely that novel, targeted medical therapies will be developed to treat CD. C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Tritos, Nicholas A.; Biller, Beverly M. K.] Harvard Univ, Sch Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA. EM ntritos@partners.org FU Pfizer; Ipsen; Novartis; Corcept FX Dr. Tritos has served as the principal investigator of research sponsored by Pfizer and Ipsen, has consulted for Pfizer and participated in scientific advisory board meetings organized by Pfizer and Corcept Therapeutics. Dr. Biller has served as the principal investigator of Grants to the MGH Neuroendocrine Clinical Center from Novartis and Corcept and as an occasional consultant to Novartis and HRA Pharma. NR 49 TC 12 Z9 13 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2014 VL 117 IS 3 SI SI BP 407 EP 414 DI 10.1007/s11060-013-1269-1 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH3LK UT WOS:000336024700004 PM 24146187 ER PT J AU Awad, AJ Rowland, NC Mian, M Hiniker, A Tate, M Aghi, MK AF Awad, Ahmed J. Rowland, Nathan Christopher Mian, Matthew Hiniker, Annie Tate, Matthew Aghi, Manish Kumar TI Etiology, prognosis, and management of secondary pituitary abscesses forming in underlying pituitary adenomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Meningitis; Pituitary abscess; Pituitary adenoma; Transsphenoidal ID INFECTION; DIAGNOSIS; APOPLEXY; SERIES; MRI AB Pituitary abscesses occurring in pre-existing pituitary pathology like Rathke's cleft cyst or adenomas (secondary pituitary abscesses) are rare and of unclear etiology. While surgery and antibiotics have been effective in some cases reported to date, leading to the suggestion that secondary pituitary abscesses are mostly indolent, we investigated the hypothesis that infected adenomas, given their propensity to invade the paranasal sinuses and subarachnoid space, could carry a worse prognosis than uninfected adenomas or secondary abscesses forming in other pituitary pathologies. We identified infected adenomas from our center through retrospective review. Given the rarity of this diagnosis at any single center, we also reviewed published cases of secondary pituitary abscesses occurring in pituitary adenomas to look for common features. Twenty-three cases (19 from the literature and four from our center) of infected adenomas were identified. The mean age at presentation was 46 years, with 65 % male. The most common presenting symptoms were visual disturbances (83 %) and headache (65 %), followed by infectious signs like fever (39 %) and meningitis (26 %). The sphenoidal sinus was the most common site of extrasellar invasion. While good outcome occurred in 74 % of patients, and most achieved vision improvement, the mortality was 26 %. Patients with infected pituitary adenomas commonly present with visual disturbances and headache, with symptoms of infection also occurring. Surgery and antibiotics are indicated for these lesions. While the infection is more indolent than other intracranial abscesses, it is associated with high mortality even after prompt operation and antibiotic treatment. C1 [Awad, Ahmed J.] An Najah Natl Univ, Fac Med & Hlth Sci, Nablus, Israel. [Rowland, Nathan Christopher; Tate, Matthew; Aghi, Manish Kumar] Univ Calif San Francisco, Dept Neurol Surg, Calif Ctr Pituitary Disorders, San Francisco, CA 94143 USA. [Mian, Matthew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Surg, Boston, MA USA. [Hiniker, Annie] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Aghi, Manish Kumar] Univ Calif San Francisco, Dept Neurol Surg, Ctr Minimally Invas Skull Base Surg, San Francisco, CA 94143 USA. RP Aghi, MK (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Calif Ctr Pituitary Disorders, 505 Parnassus Ave,Rm M-779, San Francisco, CA 94143 USA. EM aghim@neurosurg.ucsf.edu NR 35 TC 3 Z9 3 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2014 VL 117 IS 3 SI SI BP 469 EP 476 DI 10.1007/s11060-013-1285-1 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH3LK UT WOS:000336024700011 PM 24185442 ER PT J AU Coit, DG Thompson, JA Andtbacka, R Anker, CJ Bichakjian, CK Carson, WE Daniels, GA Daud, A DiMaio, D Fleming, MD Gonzalez, R Guild, V Halpern, AC Hodi, S Kelley, MC Khushalani, NI Kudchadkar, RR Lange, JR Martini, MC Olszanski, AJ Ross, MI Salama, A Swetter, SM Tanabe, KK Trisal, V Urist, MM McMillian, NR Ho, M AF Coit, Daniel G. Thompson, John A. Andtbacka, Robert Anker, Christopher J. Bichakjian, Christopher K. Carson, William E., III Daniels, Gregory A. Daud, Adil DiMaio, Dominick Fleming, Martin D. Gonzalez, Rene Guild, Valerie Halpern, Allan C. Hodi, Stephen, Jr. Kelley, Mark C. Khushalani, Nikhil I. Kudchadkar, Ragini R. Lange, Julie R. Martini, Mary C. Olszanski, Anthony J. Ross, Merrick I. Salama, April Swetter, Susan M. Tanabe, Kenneth K. Trisal, Vijay Urist, Marshall M. McMillian, Nicole R. Ho, Maria TI Melanoma, Version 4.2014 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RADIATION-THERAPY; ADJUVANT RADIOTHERAPY; METASTATIC MELANOMA; CUTANEOUS MELANOMA; IMPROVED SURVIVAL; MEK INHIBITION; OPEN-LABEL; HIGH-RISK; PHASE-II; BRAF AB The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease. C1 [Coit, Daniel G.; Halpern, Allan C.] Univ Utah, Mem Sloan Kettering Canc Ctr, Salt Lake City, UT 84112 USA. [Thompson, John A.] Univ Utah, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Salt Lake City, UT 84112 USA. [Andtbacka, Robert; Anker, Christopher J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bichakjian, Christopher K.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Carson, William E., III] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Carson, William E., III] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Daniels, Gregory A.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Daud, Adil] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [DiMaio, Dominick] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Fleming, Martin D.] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Gonzalez, Rene] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Guild, Valerie] Aim Melanoma, Richmond, CA USA. [Hodi, Stephen, Jr.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Kelley, Mark C.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Khushalani, Nikhil I.] Roswell Pk Canc Inst, Buffalo, NY USA. [Kudchadkar, Ragini R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Lange, Julie R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Martini, Mary C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Olszanski, Anthony J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Ross, Merrick I.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Salama, April] Duke Canc Inst, Durham, NC USA. [Swetter, Susan M.] Stanford Canc Inst, Stanford, CA USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Trisal, Vijay] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Urist, Marshall M.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. RP Coit, DG (reprint author), Univ Utah, Mem Sloan Kettering Canc Ctr, Salt Lake City, UT 84112 USA. RI Carson, William/E-2846-2011 NR 22 TC 28 Z9 29 U1 0 U2 3 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 MAY PY 2014 VL 12 IS 5 BP 621 EP 629 PG 9 WC Oncology SC Oncology GA AG9DJ UT WOS:000335718600004 PM 24812131 ER PT J AU Gafter-Gvili, A Steensma, DP Auerbach, M AF Gafter-Gvili, Anat Steensma, David P. Auerbach, Michael TI Should the ASCO/ASH Guidelines for the Use of Intravenous Iron in Cancer- and Chemotherapy-Induced Anemia Be Updated? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ERYTHROPOIESIS-STIMULATING AGENTS; RECOMBINANT-HUMAN-ERYTHROPOIETIN; EVERY 3 WEEKS; DARBEPOETIN-ALPHA; RANDOMIZED-TRIAL; BREAST-CANCER; EPOETIN-ALPHA; METAANALYSIS; MULTICENTER; SUPPLEMENTATION AB Coadministration of intravenous (IV) iron improves responses to erythropoiesis-stimulating agents (ESAs) in the treatment of cancer-associated (CAA) and chemotherapy-induced anemia (CIA). Twelve prospective studies have demonstrated synergy between parenteral iron and ESAs, with variable degrees of improved hemoglobin (Hgb) response rates, shorter times to target Hgb levels, and a lower ESA dose required for equivalent Hgb responses. Clinically significant adverse events (AEs) with currently available IV iron products are uncommon. Pretreatment serum hepcidin levels may predict response magnitude. Safety concerns among many oncologists are driven by reports of serious AEs from older IV iron formulations that are no longer available, and misinterpretation of the nature and frequency of minor infusion reactions. Premedication with antihistamines is of unproven benefit and can cause symptoms that mimic anaphylaxis, prompting intervention with vasopressors and converting self-limited reactions into hemodynamically significant AEs. Payer rules proscribing the administration of ESAs and IV iron on the same day also have limited the clinical adoption of IV iron and ESA coadministration. At a time when financial resources are scarce, the ability to reduce use of costly ESAs is beneficial. Despite a favorable risk/benefit ratio for IV iron in CAA and CIA, current IV iron recommendations in guidelines from ASCO/ASH, NCCN, and ESMO are inconsistent. The authors believe more routine use of IV iron for CAA and CIA is appropriate in view of existing evidence, and suggest reconsideration of the current ASCO/ASH guidelines, which state "there is insufficient evidence to consider the use of intravenous iron as a standard of care." C1 [Gafter-Gvili, Anat] Inst Hematol, Davidoff Canc Ctr, Rabin Med Ctr, Petah Tiqwa, Israel. [Gafter-Gvili, Anat] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Auerbach, Michael] Georgetown Univ, Sch Med, Baltimore, MD 21237 USA. RP Auerbach, M (reprint author), Georgetown Univ, Sch Med, 5233 King Ave 308, Baltimore, MD 21237 USA. EM mauerbachmd@abhemonc.com OI Steensma, David/0000-0001-5130-9284 NR 35 TC 7 Z9 7 U1 0 U2 1 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 MAY PY 2014 VL 12 IS 5 BP 657 EP 664 PG 8 WC Oncology SC Oncology GA AG9DJ UT WOS:000335718600007 PM 24812134 ER PT J AU Mohler, JL Kantoff, PW Armstrong, AJ Bahnson, RR Cohen, M D'Amico, AV Eastham, JA Enke, CA Farrington, TA Higano, CS Horwitz, EM Kane, CJ Kawachi, MH Kuettel, M Kuzel, TM Lee, RJ Malcolm, AW Miller, D Plimack, ER Pow-Sang, JM Raben, D Richey, S Roach, M Rohren, E Rosenfeld, S Schaeffer, E Small, EJ Sonpavde, G Srinivas, S Stein, C Strope, SA Tward, J Shead, DA Ho, M AF Mohler, James L. Kantoff, Philip W. Armstrong, Andrew J. Bahnson, Robert R. Cohen, Michael D'Amico, Anthony Victor Eastham, James A. Enke, Charles A. Farrington, Thomas A. Higano, Celestia S. Horwitz, Eric Mark Kane, Christopher J. Kawachi, Mark H. Kuettel, Michael Kuzel, Timothy M. Lee, Richard J. Malcolm, Arnold W. Miller, David Plimack, Elizabeth R. Pow-Sang, Julio M. Raben, David Richey, Sylvia Roach, Mack, III Rohren, Eric Rosenfeld, Stan Schaeffer, Edward Small, Eric J. Sonpavde, Guru Srinivas, Sandy Stein, Cy Strope, Seth A. Tward, Jonathan Shead, Dorothy A. Ho, Maria TI Prostate Cancer, Version 2.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID EXTERNAL-BEAM RADIOTHERAPY; DOSE-RATE BRACHYTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; STEREOTACTIC BODY RADIOTHERAPY; ANDROGEN DEPRIVATION THERAPY; QUALITY-OF-LIFE; PHASE-III TRIAL; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; PERMANENT INTERSTITIAL BRACHYTHERAPY; ASSISTED LAPAROSCOPIC PROSTATECTOMY AB Prostate cancer has surpassed lung cancer as the most common cancer in men in the United States. The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer based on clinical evidence and expert consensus. NCCN Panel guidance on treatment decisions for patients with localized disease is represented in this version. Significant updates for early disease include distinction between active surveillance and observation, a new section on principles of imaging, and revisions to radiation recommendations. The full version of these guidelines, including treatment of patients with advanced disease, can be found online at the NCCN website. C1 [Mohler, James L.; Kuettel, Michael] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kantoff, Philip W.; D'Amico, Anthony Victor] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Armstrong, Andrew J.] Duke Canc Inst, Durham, NC USA. [Bahnson, Robert R.] Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Bahnson, Robert R.] Solove Res Inst, Columbus, OH USA. [Cohen, Michael] Huntsman Canc Inst, Salt Lake City, UT USA. [Cohen, Michael; Tward, Jonathan] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Eastham, James A.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Enke, Charles A.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Higano, Celestia S.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Horwitz, Eric Mark; Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Kane, Christopher J.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Kawachi, Mark H.; Stein, Cy] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Kuzel, Timothy M.] Northwestern Univ, Robert H Laurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lee, Richard J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malcolm, Arnold W.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Miller, David] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Pow-Sang, Julio M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Raben, David] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Richey, Sylvia] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Roach, Mack, III; Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Rosenfeld, Stan] Univ Calif San Francisco, Urol Patient Serv Comm, San Francisco, CA 94143 USA. [Schaeffer, Edward] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Sonpavde, Guru] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Srinivas, Sandy] Stanford Canc Inst, Stanford, CA USA. [Strope, Seth A.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Strope, Seth A.] Univ Washington, Siteman Canc Ctr, Seattle, WA 98195 USA. RP Mohler, JL (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 177 TC 151 Z9 157 U1 1 U2 13 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 MAY PY 2014 VL 12 IS 5 BP 686 EP 718 PG 33 WC Oncology SC Oncology GA AG9DJ UT WOS:000335718600010 PM 24812137 ER PT J AU Payne, VL Singh, H Meyer, AND Levy, L Harrison, D Graber, ML AF Payne, Velma L. Singh, Hardeep Meyer, Ashley N. D. Levy, Lewis Harrison, David Graber, Mark L. TI Patient-Initiated Second Opinions: Systematic Review of Characteristics and Impact on Diagnosis, Treatment, and Satisfaction SO MAYO CLINIC PROCEEDINGS LA English DT Review ID CANCER-PATIENTS; ALTERNATIVE MEDICINE; ANATOMIC PATHOLOGY; SURGICAL PATHOLOGY; ERRORS; NEURORADIOLOGY; 2ND-OPINION; CARE; INTERVENTIONS; CONSULTATION AB The impact of second opinions on diagnosis in radiology and pathology is well documented; however, the value of patient-initiated second opinions for diagnosis and treatment in general medical practice is unknown. We conducted a systematic review of patient-initiated second opinions to assess their impact on clinical outcomes and patient satisfaction and to determine characteristics and motivating factors of patients who seek a second opinion. We searched PubMed, EMBASE, Cochrane, and Academic OneFile databases using Medical Subject Headings (MeSH) indexes and keyword searches. Search terms included referral and consultation, patient-initiated, patient preference, patient participation, second opinion, second review, and diagnosis. Multiple reviewers screened abstracts and articles to determine eligibility and extract data. We assessed risk of bias using the Cochrane Risk of Bias Tool and rated study quality using Cochrane's GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. We screened 1342 abstracts and reviewed full text of 41 articles, identifying 7 articles that reported clinical agreement data and 10 that discussed patient characteristics, motivation, and satisfaction. We found that a second opinion typically confirms the original diagnosis or treatment regimen but that 90% of patients with poorly defined conditions remain undiagnosed. However, 10% to 62% of second opinions yield a major change in the diagnosis, treatment, or prognosis. A larger fraction of patients receive different advice on treatment than on diagnosis. Factors motivating a second opinion include diagnosis or treatment confirmation, dissatisfaction with a consultation, desire for more information, persistent symptoms, or treatment complications. Patients generally believed that second opinions were valuable. Second opinions can result in diagnostic and treatment differences. The literature on patient-initiated second opinions is limited, and the accuracy of the second opinion through follow-up is generally unknown. Standardized methods and outcome measures are needed to determine the value of second opinions, and the potential of second opinions to reduce diagnostic errors merits more rigorous evaluation. (C) 2014 Mayo Foundation for Medical Education and Research C1 [Payne, Velma L.; Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Houston Vet Affairs Hlth Serv, Res & Dev Ctr Innovat Qual Effectiveness & Safety, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Payne, Velma L.; Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Levy, Lewis; Harrison, David] Best Doctors Inc, Boston, MA USA. [Graber, Mark L.] RTI Int, Res Triangle Pk, NC USA. RP Graber, ML (reprint author), 1 Breezy Hollow, St James, NY 11780 USA. EM mgraber@rti.org OI Graber, Mark/0000-0002-3600-0446; Meyer, Ashley/0000-0001-7993-8584 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [CIN 13-413]; Center for Innovations in Quality, Effectiveness and Safety; VA Office of Academic Affiliations, Washington; Houston VA Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX This work was supported in part by grant CIN 13-413 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and the Center for Innovations in Quality, Effectiveness and Safety. Dr Payne is supported by the VA Office of Academic Affiliations, Washington, DC. Drs Singh and Meyer are supported by the Houston VA Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 56 TC 7 Z9 7 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAY PY 2014 VL 89 IS 5 BP 687 EP 696 DI 10.1016/j.mayocp.2014.02.015 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AG6WU UT WOS:000335560400016 PM 24797646 ER PT J AU Fiskus, W Sharma, S Qi, J Valenta, JA Schaub, LJ Shah, B Peth, K Portier, BP Rodriguez, M Devaraj, SGT Zhan, M Sheng, JT Iyer, SP Bradner, JE Bhalla, KN AF Fiskus, Warren Sharma, Sunil Qi, Jun Valenta, John A. Schaub, Leasha J. Shah, Bhavin Peth, Karissa Portier, Bryce P. Rodriguez, Melissa Devaraj, Santhana G. T. Zhan, Ming Sheng, Jianting Iyer, Swaminathan P. Bradner, James E. Bhalla, Kapil N. TI Highly Active Combination of BRD4 Antagonist and Histone Deacetylase Inhibitor against Human Acute Myelogenous Leukemia Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; THERAPEUTIC TARGET; TRANSCRIPTIONAL REGULATION; HEMATOLOGIC MALIGNANCIES; BROMODOMAIN INHIBITION; SELECTIVE-INHIBITION; BET BROMODOMAINS; AML CELLS; C-MYC; CANCER AB The bromodomain and extra-terminal (BET) protein family members, including BRD4, bind to acetylated lysines on histones and regulate the expression of important oncogenes, for example, c-MYC and BCL2. Here, we demonstrate the sensitizing effects of the histone hyperacetylation-inducing pan-histone deacetylase (HDAC) inhibitor panobinostat on human acute myelogenous leukemia (AML) blast progenitor cells (BPC) to the BET protein antagonist JQ1. Treatment with JQ1, but not its inactive enantiomer (R-JQ1), was highly lethal against AML BPCs expressing mutant NPM1c+ with or without coexpression of FLT3-ITD or AML expressing mixed lineage leukemia fusion oncoprotein. JQ1 treatment reduced binding of BRD4 and RNA polymerase II to the DNA of c-MYC and BCL2 and reduced their levels in the AML cells. Cotreatment with JQ1 and the HDAC inhibitor panobinostat synergistically induced apoptosis of the AML BPCs, but not of normal CD34(+) hematopoietic progenitor cells. This was associated with greater attenuation of c-MYC and BCL2, while increasing p21, BIM, and cleaved PARP levels in the AML BPCs. Cotreatment with JQ1 and panobinostat significantly improved the survival of the NOD/SCID mice engrafted with OCI-AML3 or MOLM13 cells (P < 0.01). These findings highlight cotreatment with a BRD4 antagonist and an HDAC inhibitor as a potentially efficacious therapy of AML. (C) 2014 AACR. C1 [Fiskus, Warren; Valenta, John A.; Schaub, Leasha J.; Shah, Bhavin; Peth, Karissa; Portier, Bryce P.; Rodriguez, Melissa; Devaraj, Santhana G. T.; Zhan, Ming; Sheng, Jianting; Iyer, Swaminathan P.; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX 77030 USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bhalla, KN (reprint author), Houston Methodist Res Inst, 6670 Bertner Ave,R9-113, Houston, TX 77030 USA. EM knbhalla@tmhs.org FU NCI NIH HHS [P30 CA016672] NR 33 TC 46 Z9 47 U1 4 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2014 VL 13 IS 5 BP 1142 EP 1154 DI 10.1158/1535-7163.MCT-13-0770 PG 13 WC Oncology SC Oncology GA AH2OU UT WOS:000335961600011 PM 24435446 ER PT J AU Liu, SH Walker, SR Nelson, EA Cerulli, R Xiang, M Toniolo, PA Qi, J Stone, RM Wadleigh, M Bradner, JE Frank, DA AF Liu, Suhu Walker, Sarah R. Nelson, Erik A. Cerulli, Robert Xiang, Michael Toniolo, Patricia A. Qi, Jun Stone, Richard M. Wadleigh, Martha Bradner, James E. Frank, David A. TI Targeting STAT5 in Hematologic Malignancies through Inhibition of the Bromodomain and Extra-Terminal (BET) Bromodomain Protein BRD2 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE INHIBITORS; SIGNAL TRANSDUCER; MYELOID-LEUKEMIA; C-MYC; TRANSCRIPTION; GENE; EXPRESSION; CELLS; IDENTIFICATION AB The transcription factor signal STAT5 is constitutively activated in a wide range of leukemias and lymphomas, and drives the expression of genes necessary for proliferation, survival, and self-renewal. Thus, targeting STAT5 is an appealing therapeutic strategy for hematologic malignancies. Given the importance of bromodomain-containing proteins in transcriptional regulation, we considered the hypothesis that a pharmacologic bromodomain inhibitor could inhibit STAT5-dependent gene expression. We found that the small-molecule bromodomain and extra-terminal (BET) bromodomain inhibitor JQ1 decreases STAT5-dependent (but not STAT3-dependent) transcription of both heterologous reporter genes and endogenous STAT5 target genes. JQ1 reduces STAT5 function in leukemia and lymphoma cells with constitutive STAT5 activation, or inducibly activated by cytokine stimulation. Among the BET bromodomain subfamily of proteins, it seems that BRD2 is the critical mediator for STAT5 activity. In experimental models of acute T-cell lymphoblastic leukemias, where activated STAT5 contributes to leukemia cell survival, Brd2 knockdown or JQ1 treatment shows strong synergy with tyrosine kinase inhibitors (TKI) in inducing apoptosis in leukemia cells. In contrast, mononuclear cells isolated form umbilical cord blood, which is enriched in normal hematopoietic precursor cells, were unaffected by these combinations. These findings indicate a unique functional association between BRD2 and STAT5, and suggest that combinations of JQ1 and TKIs may be an important rational strategy for treating leukemias and lymphomas driven by constitutive STAT5 activation. (C) 2014 AACR. C1 [Liu, Suhu; Walker, Sarah R.; Nelson, Erik A.; Cerulli, Robert; Xiang, Michael; Toniolo, Patricia A.; Qi, Jun; Stone, Richard M.; Wadleigh, Martha; Bradner, James E.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Liu, Suhu; Walker, Sarah R.; Nelson, Erik A.; Cerulli, Robert; Xiang, Michael; Toniolo, Patricia A.; Qi, Jun; Stone, Richard M.; Wadleigh, Martha; Bradner, James E.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Liu, Suhu; Walker, Sarah R.; Nelson, Erik A.; Cerulli, Robert; Xiang, Michael; Toniolo, Patricia A.; Qi, Jun; Stone, Richard M.; Wadleigh, Martha; Bradner, James E.; Frank, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Toniolo, Patricia A.] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, Brazil. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM david_frank@dfci.harvard.edu FU NIH [R01-CA160979]; Lymphoma Research Foundation; Gabrielle's Angel Foundation; Brent Leahey Fund; Kittredge Foundation; Joan Harris Cancer Foundation; Leukemia & Lymphoma Society; American Society of Hematology FX This work was supported by NIH grant R01-CA160979, the Lymphoma Research Foundation, Gabrielle's Angel Foundation, the Brent Leahey Fund, the Kittredge Foundation, and the Joan Harris Cancer Foundation (to D. A. Frank), and the Leukemia & Lymphoma Society and the American Society of Hematology (to J.E. Bradner). NR 38 TC 21 Z9 21 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2014 VL 13 IS 5 BP 1194 EP 1205 DI 10.1158/1535-7163.MCT-13-0341 PG 12 WC Oncology SC Oncology GA AH2OU UT WOS:000335961600015 PM 24435449 ER PT J AU Decker, S Finter, J Forde, AJ Kissel, S Schwaller, J Mack, TS Kuhn, A Gray, N Follo, M Jumaa, H Burger, M Zirlik, K Pfeifer, D Miduturu, CV Eibel, H Veelken, H Dierks, C AF Decker, Sarah Finter, Johannes Forde, Aaron James Kissel, Sandra Schwaller, Juerg Mack, Thomas Sebastian Kuhn, Anabel Gray, Nathanael Follo, Marie Jumaa, Hassan Burger, Meike Zirlik, Katja Pfeifer, Dietmar Miduturu, Chandrasekhar V. Eibel, Hermann Veelken, Hendrik Dierks, Christine TI PIM Kinases Are Essential for Chronic Lymphocytic Leukemia Cell Survival (PIM2/3) and CXCR4-Mediated Microenvironmental Interactions (PIM1) SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MARROW STROMAL CELLS; GENE MUTATION STATUS; B-CELLS; CHEMOKINE RECEPTORS; IN-VITRO; C-MYC; EXPRESSION; MIGRATION; INHIBITOR; CXCR4 AB Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic leukemia (CLL) and is important for CLL cell survival, migration, and interaction with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1 was shown to regulate the surface expression of the CXCR4 receptor. Here, we show that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1-3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339 in CLL compared with normal lymphocytes. Furthermore, CXCR4 phosphorylation correlates with PIM1 protein expression and PIM1 transcript levels in CLL. PIM kinase inhibition with three different PIM kinase inhibitors induced apoptosis in CLL cells independent of the presence of protective stromal cells. In addition, PIM inhibition caused dephosphorylation of the CXCR4 receptor on Ser339, resulting in enhanced ligand-dependent CXCR4 internalization and reduced re-externalization after withdrawal of CXCL12. Furthermore, PIM inhibition in CLL cells blocked CXCR4 functions, such as migration toward CXCL12-or CXCL12-induced extracellular signal-regulated kinase (ERK) phosphorylation. In concordance, pretreatment of CLL cells with PIM kinase inhibitors strongly reduced homing of CLL cells toward the bone marrow and the spleen of Rag2(-/-) gamma c(-/-) mice in vivo. Interestingly, the knockdown of PIM kinases in CLL cells demonstrated diverging functions, with PIM1 regulating CXCR4 surface expression and PIM2 and PIM3 as important for the survival of CLL cells. Our results show that PIM kinase inhibitors are an effective therapeutic option for CLL, not only by impairing PIM2/3-mediated CLL cell survival, but also by blocking the PIM1/CXCR4-mediated interaction of CLL cells with their protective microenvironment. (C) 2014 AACR. C1 [Decker, Sarah; Finter, Johannes; Forde, Aaron James; Kissel, Sandra; Mack, Thomas Sebastian; Kuhn, Anabel; Follo, Marie; Burger, Meike; Zirlik, Katja; Pfeifer, Dietmar; Veelken, Hendrik; Dierks, Christine] Univ Med Ctr Freiburg, Dept Hematol Oncol, D-79106 Freiburg, Germany. [Eibel, Hermann] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79106 Freiburg, Germany. [Decker, Sarah; Jumaa, Hassan] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany. [Dierks, Christine] Univ Freiburg, BIOSS Ctr Biol Signaling Studies, D-79106 Freiburg, Germany. [Schwaller, Juerg] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Gray, Nathanael; Miduturu, Chandrasekhar V.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Gray, Nathanael; Miduturu, Chandrasekhar V.] Dana Faber Canc Inst, Dept Canc Biol, Boston, MA USA. [Veelken, Hendrik] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands. RP Dierks, C (reprint author), Univ Med Ctr Freiburg, Dept Hematol Oncol, Hugstetter Str 55, D-79106 Freiburg, Germany. EM christine.dierks@uniklinik-freiburg.de RI schwaller, juerg/A-3044-2016; OI Veelken, Hendrik/0000-0002-9108-3125 FU Deutsche Krebshilfe [110670]; BIOSS Centre for Biological Signalling Studies; DFG [DI 1664/1-1] FX This work was supported by the Deutsche Krebshilfe (grant 110670) to C. Dierks. H. Jumaa and C. Dierks are supported by the "BIOSS Centre for Biological Signalling Studies." The position of C. Dierks is supported by the Emmy-Noether program of the DFG (DI 1664/1-1). NR 53 TC 23 Z9 23 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2014 VL 13 IS 5 BP 1231 EP 1245 DI 10.1158/1535-7163.MCT-13-0575-T PG 15 WC Oncology SC Oncology GA AH2OU UT WOS:000335961600018 PM 24659821 ER PT J AU Yin, R Wang, M Huang, YY Huang, HC Avci, P Chiang, LY Hamblin, MR AF Yin, Rui Wang, Min Huang, Ying-Ying Huang, Huang-Chiao Avci, Pinar Chiang, Long Y. Hamblin, Michael R. TI Photodynamic therapy with decacationic [60]fullerene monoadducts: Effect of a light absorbing electron-donor antenna and micellar formulation SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Photodynamic therapy; Decacationic fullerene monoadducts; Nanomedicine; Structure-function relationship; Reactive oxygen species; Light absorbing antenna; Apoptosis; Micelles ID CREMOPHOR EL; FULLERENE DERIVATIVES; CANCER-CELLS; FUNCTIONALIZED FULLERENES; BIOLOGICAL APPLICATIONS; ENDOPLASMIC-RETICULUM; CENTRAL METAL; C-60; MECHANISMS; PHOTOSENSITIZERS AB We report the synthesis and anticancer photodynamic properties of two new decacationic fullerene (LC14) and red light-harvesting antenna-fullerene conjugated monoadduct (LC15) derivatives. The antenna of LC15 was attached covalently to C-60 > with distance of only <3.0 angstrom to facilitate ultrafast intramolecular photoinduced-electron-transfer (for type-I photochemistry) and photon absorption at longer wavelengths. Because LC15 was hydrophobic we compared formulation in Cremophor EL micelles with direct dilution from dimethylacetamide. LC14 produced more O-1(2) than LC15, while LC15 produced much more HO center dot than LC14 as measured by specific fluorescent probes. When delivered by DMA, LC14 killed more HeLa cells than LC15 when excited by UVA light, while LC15 killed more cells when excited by white light consistent with the antenna effect. However LC15 was more effective than LC14 when delivered by micelles regardless of the excitation light. Micellar delivery produced earlier apoptosis and damage to the endoplasmic reticulum as well as to lysosomes and mitochondria. From the Clinical Editor: This team of authors report the synthesis and the photodynamic properties of two new derivatives for cancer treatment; one is a decacationic fullerene (LC14) and the other is a red light-harvesting antenna-fullerene conjugated monoadduct (LC15) utilizing a HeLa cell model. (C) 2014 Elsevier Inc. All rights reserved. C1 [Yin, Rui; Huang, Ying-Ying; Huang, Huang-Chiao; Avci, Pinar; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yin, Rui; Huang, Ying-Ying; Huang, Huang-Chiao; Avci, Pinar; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China. [Wang, Min; Chiang, Long Y.] Univ Massachusetts, Dept Chem, Lowell, MA USA. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, Budapest, Hungary. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01CA137108, R01AI050875]; National Natural Science Foundation of China [81172495] FX This work was funded by US NIH grants R01CA137108 to LYC and R01AI050875 to MRH. Rui Yin was supported in part by National Natural Science Foundation of China (No. 81172495) in this work. NR 60 TC 13 Z9 14 U1 4 U2 47 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD MAY PY 2014 VL 10 IS 4 BP 795 EP 808 DI 10.1016/j.nano.2013.11.014 PG 14 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA AH3OE UT WOS:000336032800011 PM 24333585 ER PT J AU Lohr, JG Adalsteinsson, VA Cibulskis, K Choudhury, AD Rosenberg, M Cruz-Gordillo, P Francis, JM Zhang, CZ Shalek, AK Satija, R Trombetta, JJ Lu, D Tallapragada, N Tahirova, N Kim, S Blumenstiel, B Sougnez, C Lowe, A Wong, B Auclair, D Van Allen-, EM Nakabayashi, M Lis, RT Lee, GSM Li, T Chabot, MS Taplin, ME Taplin, ME Clancy, TE Loda, M Regev, A Meyerson, M Hahn, WC Kantoff, PW Golub, TR Getz, G Boehm, JS Love, JC AF Lohr, Jens G. Adalsteinsson, Viktor A. Cibulskis, Kristian Choudhury, Atish D. Rosenberg, Mara Cruz-Gordillo, Peter Francis, Joshua M. Zhang, Cheng-Zhong Shalek, Alex K. Satija, Rahul Trombetta, John J. Lu, Diana Tallapragada, Naren Tahirova, Narmin Kim, Sora Blumenstiel, Brendan Sougnez, Carrie Lowe, Alarice Wong, Bang Auclair, Daniel Van Allen-, Eliezer M. Nakabayashi, Mari Lis, Rosina T. Lee, Gwo-Shu M. Li, Tiantian Chabot, Matthew S. Ly, Amy Taplin, Mary-Ellen Clancy, Thomas E. Loda, Massimo Regev, Aviv Meyerson, Matthew Hahn, William C. Kantoff, Philip W. Golub, Todd R. Getz, Gad Boehm, Jesse S. Love, J. Christopher TI Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer SO NATURE BIOTECHNOLOGY LA English DT Article ID COPY-NUMBER; RNA-SEQ; MUTATIONAL LANDSCAPE; BREAST-CANCER; GENOME; DNA; HETEROGENEITY; PROGRESSION; EVOLUTION; FRAMEWORK AB Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of > 99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic. C1 [Lohr, Jens G.; Adalsteinsson, Viktor A.; Cibulskis, Kristian; Choudhury, Atish D.; Rosenberg, Mara; Cruz-Gordillo, Peter; Francis, Joshua M.; Zhang, Cheng-Zhong; Satija, Rahul; Trombetta, John J.; Lu, Diana; Kim, Sora; Blumenstiel, Brendan; Sougnez, Carrie; Wong, Bang; Auclair, Daniel; Van Allen-, Eliezer M.; Loda, Massimo; Regev, Aviv; Meyerson, Matthew; Hahn, William C.; Golub, Todd R.; Getz, Gad; Boehm, Jesse S.; Love, J. Christopher] Eli & Edythe L Broad Inst & Harvard, Cambridge, MA 02142 USA. [Lohr, Jens G.; Choudhury, Atish D.; Francis, Joshua M.; Zhang, Cheng-Zhong; Satija, Rahul; Trombetta, John J.; Lu, Diana; Van Allen-, Eliezer M.; Nakabayashi, Mari; Lis, Rosina T.; Lee, Gwo-Shu M.; Li, Tiantian; Chabot, Matthew S.; Meyerson, Matthew; Hahn, William C.; Kantoff, Philip W.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lohr, Jens G.; Choudhury, Atish D.; Van Allen-, Eliezer M.; Clancy, Thomas E.; Loda, Massimo; Meyerson, Matthew; Hahn, William C.; Kantoff, Philip W.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA USA. [Adalsteinsson, Viktor A.; Tallapragada, Naren; Tahirova, Narmin; Love, J. Christopher] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Shalek, Alex K.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Lowe, Alarice; Hahn, William C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ly, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Regev, Aviv] MIT, Dept Biol, Cambridge, MA USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Love, J. Christopher] Ragon Inst MGH & Harvard, Cambridge, MA USA. RP Love, JC (reprint author), Eli & Edythe L Broad Inst & Harvard, Cambridge, MA 02142 USA. EM gadgetz@broadinstitute.org; boehm@broadinstitute.org; clove@mit.edu RI Kim, Sora/D-7707-2015; OI Kim, Sora/0000-0002-9856-9574; Boehm, Jesse/0000-0002-6795-6336; Shalek, Alex K./0000-0001-5670-8778 FU Conquer Cancer Foundation Young Investigator Award; US National Institutes of Health (DF/HCC SPORE) [5P50CA100707-10]; Wong Family Award; National Science Foundation; Prostate Cancer Foundation Young Investigator Award; Department of Defense Physician Scientist Training Award FX G. L. was supported by a Conquer Cancer Foundation Young Investigator Award, US National Institutes of Health grant 5P50CA100707-10 (DF/HCC SPORE) and the Wong Family Award. V. A. A. was supported in part by a graduate fellowship from the National Science Foundation. A. D. C. is supported by the Prostate Cancer Foundation Young Investigator Award and the Department of Defense Physician Scientist Training Award. J. C. L. is a Camille Dreyfus Teacher-Scholar. We acknowledge the Arthur and Linda Gelb Center for Translational Research for the acquisition and annotation of clinical samples and A. Abbott and A. Van Den Abbeele from the Dana-Farber Cancer Institute (DFCI) Department of Imaging for positron-emission tomography (PET) images. We also acknowledge P. K. Brastianos (Department of Medical Oncology, DFCI) and I. Dunn (Department of Neurosurgery, Brigham and Women's Hospital) for contributing samples for CTC analysis, D. Peck for help with technology development, O. Voznesensky and S. Balk for purification of DNA from the metastatic tumor for sequencing, C. Whittaker and S. S. Levine for advice on sequencing and analysis and the Broad Genomics Platform for the development of new sequencing approaches used here. This work was also supported in part by the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute, and we thank the Koch Institute Swanson Biotechnology Center for technical support, specifically the BioMicroCenter. This work was also supported in part by Janssen Pharmaceuticals, Inc. and the Klarman Family Foundation. We would like to thank Illumina for providing the MagSweeper. The authors dedicate this paper to the memory of Officer Sean Collier, for his caring service to the MIT community and for his sacrifice. NR 42 TC 151 Z9 157 U1 16 U2 89 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2014 VL 32 IS 5 BP 479 EP U202 DI 10.1038/nbt.2892 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AH3PH UT WOS:000336036100024 PM 24752078 ER PT J AU Im, H Shao, HL Park, YI Peterson, VM Castro, CM Weissleder, R Lee, H AF Im, Hyungsoon Shao, Huilin Park, Yong Il Peterson, Vanessa M. Castro, Cesar M. Weissleder, Ralph Lee, Hakho TI Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor SO NATURE BIOTECHNOLOGY LA English DT Article ID EPITHELIAL OVARIAN-CANCER; PROTEIN; MARKER; MICROARRAYS; EXPRESSION; BIOMARKERS; CARCINOMA; KNOWLEDGE; SURVIVAL; EXCHANGE AB Exosomes show potential for cancer diagnostics because they transport molecular contents of the cells from which they originate. Detection and molecular profiling of exosomes is technically challenging and often requires extensive sample purification and labeling. Here we describe a label-free, high-throughput approach for quantitative analysis of exosomes. Our nano-plasmonic exosome (nPLEX) assay is based on transmission surface plasmon resonance through periodic nanohole arrays. Each array is functionalized with antibodies to enable profiling of exosome surface proteins and proteins present in exosome lysates. We show that this approach offers improved sensitivity over previous methods, enables portable operation when integrated with miniaturized optics and allows retrieval of exosomes for further study. Using nPLEX to analyze ascites samples from ovarian cancer patients, we find that exosomes derived from ovarian cancer cells can be identified by their expression of CD24 and EpCAM, suggesting the potential of exosomes for diagnostics. C1 [Im, Hyungsoon; Shao, Huilin; Park, Yong Il; Peterson, Vanessa M.; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU US National Institutes of Health (NIH) [R01-HL113156, R01-EB010011, R01-EB00462605A1, T32CA79443, K12CA087723-11A1]; National Heart, Lung, and Blood Institute [HHSN268201000044C]; Center for Nanoscale Systems (CNS) at Harvard University (National Science Foundation award) [ECS-0335765] FX The authors thank S. Skates (Massachusetts General Hospital) for helpful discussion on statistical analyses; M. Birrer for facilitating sample collection; K. Joyes for reviewing the manuscript. This work was supported in part by US National Institutes of Health (NIH) grants R01-HL113156 (H.L.), R01-EB010011 (R.W.), R01-EB00462605A1 (R.W.), T32CA79443 (R.W.), K12CA087723-11A1 (C.M.C) and National Heart, Lung, and Blood Institute contract HHSN268201000044C (R.W.). The device was fabricated using the facilities at the Center for Nanoscale Systems (CNS) at Harvard University (National Science Foundation award ECS-0335765). NR 36 TC 130 Z9 131 U1 40 U2 241 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2014 VL 32 IS 5 BP 490 EP U219 DI 10.1038/nbt.2886 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AH3PH UT WOS:000336036100026 PM 24752081 ER PT J AU Reardon, DA Wen, PY AF Reardon, David A. Wen, Patrick Y. TI Further delineating bevacizumab's response spectrum SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID NEWLY-DIAGNOSED GLIOBLASTOMA; TUMOR VASCULATURE; RADIOTHERAPY; TEMOZOLOMIDE; SURVIVAL; TRIAL AB The use of antiangiogenic drugs, such as bevacizumab, represents an appealing intervention against cancer. However, not all malignancies are equally responsive to such treatment. Recent trials demonstrate the efficacy of this drug for advanced-stage cervical cancer and, despite limitations, bevacizumab provides an important clinical respite for most patients with progressive glioblastoma. C1 [Reardon, David A.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Dept Med Oncol, Boston, MA 02215 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu NR 10 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2014 VL 11 IS 5 BP 243 EP 244 DI 10.1038/nrclinonc.2014.61 PG 2 WC Oncology SC Oncology GA AH1VL UT WOS:000335909200001 PM 24710578 ER PT J AU Sobrin, L Seddon, JM AF Sobrin, Lucia Seddon, Johanna M. TI Nature and nurture- genes and environment- predict onset and progression of macular degeneration SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Age-related macular degeneration; Epidemiology; Genetics; Risk factors ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; C-REACTIVE PROTEIN; BODY-MASS INDEX; HEMOLYTIC-UREMIC SYNDROME; GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; DENSE DEPOSIT DISEASE; BLUE-MOUNTAINS-EYE; RISK-FACTORS AB Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including antioxidants and dietary fat intake influence onset and progression of AMD. There are also several lines of evidence that link cardiovascular, immune and inflammatory biomarkers to AMD. The genetic etiology of AMD has been and continues to be an intense and fruitful area of investigation. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing our knowledge of how rare genetic variants strongly impact disease. Evidence for interactions between environmental, therapeutic and genetic factors is emerging and elucidating the mechanisms of this interplay remains a major challenge in the field. Genotype-phenotype associations are evolving. The knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and our ability to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future. (C) 2014 Published by Elsevier Ltd. C1 [Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. RP Seddon, JM (reprint author), Tufts Med Ctr, 800 Washington St 450, Boston, MA 02111 USA. EM jseddon@tuftsmedicalcenter.org FU National Institutes of Health [K12-EY16335, R01-EY11309]; Massachusetts Lions Eye Research Fund, Inc.; Foundation Fighting Blindness; Macular Vision Research Foundation; Research to Prevent Blindness Career Development Award; Research to Prevent Blindness Challenge Grant; Department of Ophthalmology; Tufts University School of Medicine; American Macular Degeneration Foundation; Arnold and Mabel Beckman Initiative for Macular Research; Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service; New England Eye Center; Tufts Medical Center FX This research was supported by grants K12-EY16335 and R01-EY11309 from the National Institutes of Health; Massachusetts Lions Eye Research Fund, Inc.; the Foundation Fighting Blindness; the Macular Vision Research Foundation; Research to Prevent Blindness Career Development Award; Research to Prevent Blindness Challenge Grant to the New England Eye Center, Department of Ophthalmology, Tufts University School of Medicine; American Macular Degeneration Foundation; The Arnold and Mabel Beckman Initiative for Macular Research; and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine. NR 172 TC 30 Z9 30 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD MAY PY 2014 VL 40 BP 1 EP 15 DI 10.1016/j.preteyeres.2013.12.004 PG 15 WC Ophthalmology SC Ophthalmology GA AH3EK UT WOS:000336006200001 PM 24374240 ER PT J AU Pennock, S Haddock, LJ Eliott, D Mukai, S Kazlauskas, A AF Pennock, Steven Haddock, Luis J. Eliott, Dean Mukai, Shizuo Kazlauskas, Andrius TI Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy? SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Proliferative vitreoretinopathy; Retinal detachment; Vitreous; Growth factors; Signaling; PDGFR ID PIGMENT EPITHELIAL-CELLS; RHEGMATOGENOUS RETINAL-DETACHMENT; PDGF-BETA-RECEPTOR; COLLAGEN GEL CONTRACTION; SMOOTH-MUSCLE-CELLS; PROTEIN 2 EMP2; MASSIVE PERIRETINAL PROLIFERATION; RANDOMIZED CONTROLLED-TRIAL; MOLECULAR-WEIGHT HEPARIN; FACTOR-ALPHA RECEPTOR AB Proliferative vitreoretinopathy (PVR) is a blinding disorder that occurs in eyes with rhegmatogenous retinal detachment and in eyes that have recently undergone retinal detachment surgery. There are presently no treatment strategies to reduce the risk of developing PVR in eyes with retinal detachment, and surgical intervention is the only option for eyes with retinal detachment and established PVR. Given the poor visual outcome associated with the surgical treatment of PVR, considerable work has been done to identify pharmacologic agents that could antagonize the PVR process. Intensive efforts to identify molecular determinants of PVR implicate vitreal growth factors. A surprise that emerged in the course of testing the 'growth factor hypothesis' of PVR was the existence of a functional relationship amongst growth factors that engage platelet-derived growth factor (PDGF) receptor alpha (PDGFR alpha), a receptor tyrosine kinase that is key to pathogenesis of experimental PVR. Vascular endothelial cell growth factor A (VEGF), which is best known for its ability to activate VEGF receptors (VEGFRs) and induce permeability and/or angiogenesis, enables activation of PDGFRa by a wide spectrum of vitreal growth factors outside of the PDGF family (non-PDGFs) in a way that triggers signaling events that potently enhance the viability of cells displaced-into vitreous. Targeting these-growth-factors-or signaling. ements_effectively neutralizes the bioactivity of PVR vitreous and prevents PVR in a number of preclinical models. In this review, we discuss recent conceptual advances in understanding the role of growth factors in PVR, and consider the tangible treatment strategies for clinical application. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Pennock, Steven; Haddock, Luis J.; Eliott, Dean; Mukai, Shizuo; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu FU Department of Defense [WB1XWH-10-1-0392]; NIH [EY012509]; Mukai Fund of the Massachusetts Eye and Ear Infirmary (Boston); Canadian Institutes of Health Research (CIHR) FX Funding for this research was provided by grants from the Department of Defense grant WB1XWH-10-1-0392 and NIH grant EY012509 (A.K.), Mukai Fund of the Massachusetts Eye and Ear Infirmary (Boston) gifts (S.M.), and fellowship support from the Canadian Institutes of Health Research (CIHR) (S.P.). NR 179 TC 28 Z9 29 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD MAY PY 2014 VL 40 BP 16 EP 34 DI 10.1016/j.preteyeres.2013.12.006 PG 19 WC Ophthalmology SC Ophthalmology GA AH3EK UT WOS:000336006200002 PM 24412519 ER PT J AU Kostin, A Siegel, JM Alam, MN AF Kostin, Andrey Siegel, Jerome M. Alam, Md. Noor TI Lack of Hypocretin Attenuates Behavioral Changes Produced by Glutamatergic Activation of the Perifornical-Lateral Hypothalamic Area SO SLEEP LA English DT Article DE orexin; hypocretin; perifornical area; prepro-orexin knockout; sleep; dorsomedial hypothalamus; lateral hypothalamus; N-methyl-D-aspartate ID OREXIN KNOCKOUT MICE; OREXIN/HYPOCRETIN NEURONS; SLEEP REGULATION; MOUSE MODELS; MCH NEURONS; NARCOLEPSY; WAKEFULNESS; RATS; DISCHARGE; WAKING AB Study Objectives: The hypocretins (HCRTs) are two hypothalamic peptides predominantly localized to neurons in the perifornical, dorsomedial, and lateral hypothalamic area (PF-LHA). Evidence suggests that HCRT signaling is critical for the promotion and stabilization of active-arousal and its loss or malfunction leads to symptoms of narcolepsy. In the PF-LHA, HCRT neurons are intermingled with glutamate-expressing neurons and also co-express glutamate. Evidence suggests that HCRT-glutamate interactions within the PF-LHA may play a critical role in maintaining behavioral arousal. However, the relative contributions of the glutamate and HCRT in sleep-wake regulation are not known. Design: We determined whether a lack of HCRT signaling in the prepro-orexin-knockout (HCRT-KO) mouse attenuates/compromises the wake-promoting ability of glutamatergic activation of the PF-LHA region. We used reverse microdialysis to deliver N-methyl-D-aspartate (NMDA) into the HCRT zone of the PF-LHA in HCRT-KO and wild-type (WT) mice to evaluate the contributions of glutamatergic vs. HCRT signaling in sleep-wake regulation. Measurements and Results: As compared to respective controls, local perfusion of NMDA into the PF-LHA, dose-dependently increased active-waking with concomitant reductions in nonREM and REM sleep in spontaneously sleeping WT as well as HCRT-KO mice. However, compared to WT, the NMDA-induced behavioral changes in HCRT-KO mice were significantly attenuated, as evidenced by the higher dose of NMDA needed and lower magnitude of changes induced in sleep-wake parameters. Although not observed in WT mice, the number of cataplectic events increased significantly during NMDA-induced behavioral arousal in HCRT-KO mice. Conclusions: The findings of this study are consistent with a hypothesis that synergistic interactions between hypocretin and glutamatergic mechanisms within the perifornical, dorsomedial, and lateral hypothalamic area are critical for maintaining behavioral arousal, especially arousal involving elevated muscle tone. C1 [Kostin, Andrey; Siegel, Jerome M.; Alam, Md. Noor] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151A3, Sepulveda, CA 91343 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Alam, Md. Noor] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Alam, MN (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, Sepulveda, CA 91343 USA. EM noor@ucla.edu FU Medical Research Service, US Department of Veterans Affairs [MH064109] FX This was not an industry supported study. This work was supported by the Medical Research Service, US Department of Veterans Affairs and MH064109. The authors have indicated no financial conflicts of interest. NR 55 TC 7 Z9 7 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD MAY 1 PY 2014 VL 37 IS 5 BP 1011 EP 1020 DI 10.5665/sleep.3680 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH3UZ UT WOS:000336052600023 PM 24790280 ER PT J AU Williams, DA Thrasher, AJ AF Williams, David A. Thrasher, Adrian J. TI Concise Review: Lessons Learned From Clinical Trials of Gene Therapy in Monogenic Immunodeficiency Diseases SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Review DE Clinical trials; Gene therapy; Immunodeficiency; Hematopoietic cells; Progenitor cells ID CHRONIC GRANULOMATOUS-DISEASE; ADENOSINE-DEAMINASE DEFICIENCY; WISKOTT-ALDRICH SYNDROME; INTEGRATION SITE SELECTION; RETROVIRAL VECTOR INSERTION; LEUKEMIA-VIRUS INTEGRATION; STEM-CELL TRANSPLANTATION; HEMATOPOIETIC-CELLS; GAMMARETROVIRAL VECTOR; REPOPULATING CELLS AB Thirty years ago, retroviral transfer of genetic material into hematopoietic stem and progenitor cells (HSC/Ps) led to predictions that this technology would transform modern medicine [Nature 1983;305: 556-558; Nature 1984;310:476-480]. Studies in several immunodeficiency diseases in the past 15 years have demonstrated clear proof of principle that gene therapy can have long-lasting, potentially curative effects without the need to search for allogeneic donors and without risk of graft-versus-host disease. Improvement in gene transfer efficiency for target HSC/Ps brought to light issues of insertional mutagenesis caused by transfer vectors, resulting in oncogene transactivation and leukemias. Lessons from these adverse events have now led to a new generation of vectors, refinements in conditioning regimens, and manufacturing, which are paving the way for expanded applications of the current technology and recent emphasis on gene targeting/genome editing as the next advancements in the field. C1 [Williams, David A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Thrasher, Adrian J.] Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, London, England. RP Williams, DA (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM dawilliams@childrens.harvard.edu FU Wellcome Trust; National Institute of Health Research; Great Ormond Street Hospital National Health Service Trust Biomedical Research Center; Medical Research Council; [U01A1087628]; [U01HL117720]; [HLBII-S-11-001403] FX We thank Jonathan Li and Natasha Rossi for administrative assistance. A.J.T. is supported by the Wellcome Trust, National Institute of Health Research, Great Ormond Street Hospital National Health Service Trust Biomedical Research Center, and Medical Research Council; D.A.W. is supported by U01A1087628, U01HL117720, and HLBII-S-11-001403. NR 87 TC 16 Z9 16 U1 0 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD MAY PY 2014 VL 3 IS 5 BP 636 EP 642 DI 10.5966/sctm.2013-0206 PG 7 WC Cell & Tissue Engineering SC Cell Biology GA AH2GH UT WOS:000335939000020 PM 24682287 ER PT J AU Schapira, MM Mackenzie, ER Lam, R Casarett, D Seluzicki, CM Barg, FK Mao, JJ AF Schapira, Marilyn M. Mackenzie, Elizabeth R. Lam, Regina Casarett, David Seluzicki, Christina M. Barg, Frances K. Mao, Jun J. TI Breast cancer survivors willingness to participate in an acupuncture clinical trial: a qualitative study SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Breast cancer survivors; Acupuncture; Clinical trials; Decision making ID ALTERNATIVE MEDICINE USE; AFRICAN-AMERICANS; HOT FLASHES; COMPLEMENTARY; ATTITUDES; RECRUITMENT; CARE; MINORITIES; BARRIERS; ONCOLOGY AB Purpose Acupuncture is a complementary and alternative medicine (CAM) modality that shows promise as a component of supportive breast cancer care. Lack of robust recruitment for clinical trial entry has limited the evidence base for acupuncture as a treatment modality among breast cancer survivors. The objective of this study is to identify key decision-making factors among breast cancer survivors considering entry into an acupuncture clinical trial for treatment of symptoms. Methods Semistructured interviews were conducted among African-American (n = 12) and Caucasian (n = 13) breast cancer survivors. Verbatim transcripts were made and analyzed by two or more independent coders using NVivo software. Major recurring themes were identified and a theoretical framework developed. Results Six themes emerged reflecting key attributes of the decision to enter a clinical trial: (1) symptom appraisal, (2) practical barriers (e. g., distance and travel), (3) beliefs about the interventions (e. g., fear of needles and dislike of medications), (4) comfort with elements of clinical trial design (e. g., randomization, the nature of the control intervention, and blinding), (5) trust, and (6) altruism. African-American and Caucasian women weighed similar attributes but differed in the information sources sought regarding clinical trial entry and in concerns regarding the use of a placebo in a clinical trial. Conclusions Our findings contribute to the development of a theoretical model of decision making for breast cancer survivors considering participation in a CAM clinical trial. Insights regarding the decision making process can inform interventions to support informed decision making and robust recruitment to CAM trials among cancer survivors. C1 [Schapira, Marilyn M.] Univ Penn, Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.; Mao, Jun J.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mackenzie, Elizabeth R.] Univ Penn, Div Appl Psychol Human Dev, Grad Sch Educ, Philadelphia, PA 19104 USA. [Lam, Regina; Seluzicki, Christina M.; Barg, Frances K.; Mao, Jun J.] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA. [Casarett, David] Univ Penn, Dept Med, Div Geriatr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Dept Anthropol, Sch Arts & Sci, Philadelphia, PA 19104 USA. RP Schapira, MM (reprint author), Univ Penn, Abramson Canc Ctr, Perelman Sch Med, 1122 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mschap@upenn.edu FU American Cancer Society [CCCDA-08-107]; National Institute of Health/National Center for Complementary and Alternative Medicine [R21 AT004695, K23004112] FX This research is funded in part from American Cancer Society CCCDA-08-107 award. Mao is a recipient of the National Institute of Health/National Center for Complementary and Alternative Medicine grants R21 AT004695 and K23004112. The funding agencies had no role in the design and conduct of the study. NR 35 TC 3 Z9 4 U1 0 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 2014 VL 22 IS 5 BP 1207 EP 1215 DI 10.1007/s00520-013-2073-3 PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA AG9XY UT WOS:000335774600008 PM 24362843 ER PT J AU Serrano, C George, S AF Serrano, Cesar George, Suzanne TI Recent advances in the treatment of gastrointestinal stromal tumors SO THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY LA English DT Review DE c-KIT; gastrointestinal stromal tumors; imatinib; masitinib; nilotinib; regorafenib; sorafenib; sunitinib ID PHASE-II TRIAL; IMATINIB-RESISTANT MUTANTS; TERM-FOLLOW-UP; TYROSINE KINASE; SUCCINATE-DEHYDROGENASE; ACQUIRED-RESISTANCE; ADJUVANT IMATINIB; PDGFRA MUTATIONS; RANDOMIZED-TRIAL; KIT MUTATIONS AB Constitutively activating mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) RTKs play a crucial role in the biology of gastrointestinal stromal tumors (GISTs), and this disease has served as an effective model for targeting gain-of-function kinase mutations in cancer. Imatinib has entered the clinical arena in the last decade and substantially improved the outcome in these formerly untreatable cancers. However, most advanced GISTs responding to imatinib progress within 2-3 years due to heterogeneous subclones harboring a range of imatinib-resistant secondary KIT mutations. Sunitinib, and more recently, regorafenib, have obtained US Food and Drug Administration approval for the treatment of GISTs after imatinib failure, and thus expanded the treatment options in resistant disease. Within this framework, we present an evaluation of current GIST management, emphasizing the most recent advances in the field together with a discussion on future steps to be taken in refractory disease. C1 [Serrano, Cesar; George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. RP George, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM sgeorge2@partners.org FU American Society of Clinical Oncology (ASCO) FX Cesar Serrano: American Society of Clinical Oncology (ASCO) Young Investigator Award. NR 74 TC 20 Z9 20 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1758-8340 EI 1758-8359 J9 THER ADV MED ONCOL JI Ther. Adv. Med. Oncol. PD MAY PY 2014 VL 6 IS 3 BP 115 EP 127 DI 10.1177/1758834014522491 PG 13 WC Oncology SC Oncology GA AH0NQ UT WOS:000335817200003 PM 24790651 ER PT J AU Zimmerman, N Izard, J Klatt, C Zhou, JZ Aronson, E AF Zimmerman, Naupaka Izard, Jacques Klatt, Christian Zhou, Jizhong Aronson, Emma TI The unseen world: environmental microbial sequencing and identification methods for ecologists SO FRONTIERS IN ECOLOGY AND THE ENVIRONMENT LA English DT Article ID RIBOSOMAL-RNA GENE; COMMUNITY STRUCTURE; DNA; DIVERSITY; SOIL; METAGENOMES; LIBRARIES; SYSTEMS; SAMPLES AB Microorganisms inhabit almost every environment, comprise the majority of diversity on Earth, are important in biogeochemical cycling, and may be vital to ecosystem responses to large-scale climatic change. In recent years, ecologists have begun to use rapidly advancing molecular techniques to address questions about microbial diversity, biogeography, and responses to environmental change. Studies of microbes in the environment generally focus on three broad objectives: determining which organisms are present, what their functional capabilities are, and which are active at any given time. However, comprehending the range of methodologies currently in use can be daunting. To provide an overview of environmental microbial sequence data collection and analysis approaches, we include case studies of microbiomes ranging from the human mouth to geothermal springs. We also suggest contexts in which each technique can be applied and highlight insights that result from their use. C1 [Zimmerman, Naupaka] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Zimmerman, Naupaka] Univ Arizona, Sch Plant Sci, Tucson, AZ 85721 USA. [Izard, Jacques] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Klatt, Christian] Swedish Univ Agr Sci, Dept Forest Ecol & Management, S-90183 Umea, Sweden. [Zhou, Jizhong] Univ Oklahoma, Inst Environm Genom, Norman, OK 73019 USA. [Zhou, Jizhong] Univ Oklahoma, Dept Microbiol & Plant Biol, Norman, OK 73019 USA. [Zhou, Jizhong] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Earth Sci, Berkeley, CA 94720 USA. [Zhou, Jizhong] Tsinghua Univ, Sch Environm, State Key Joint Lab Environm Simulat & Pollut Con, Beijing 100084, Peoples R China. [Aronson, Emma] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA. RP Zimmerman, N (reprint author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA. EM emma.aronson@ucr.edu RI Zimmerman, Naupaka/N-9128-2015; OI Zimmerman, Naupaka/0000-0003-2168-6390; Izard, Jacques/0000-0002-5904-5436 FU NSF Graduate Research Fellowship; Gordon and Betty Moore Postdoctoral Fellowship from the Life Sciences Research Foundation; National Cancer Institute [CA166150]; NSF IGERT in Geobiological Systems [DGE 0654336]; DOE Office of Biological and Environmental Research as part of ENIGMA, a Scientific Focus Area [DE-AC02-05CH11231]; NASA Graduate Student Researchers Program Fellowship; NOAA Climate and Global Change Fellowship FX This work was funded in part by an NSF Graduate Research Fellowship and a Gordon and Betty Moore Postdoctoral Fellowship from the Life Sciences Research Foundation to NZ; a grant from the National Cancer Institute (CA166150) to JI; an NSF IGERT in Geobiological Systems (DGE 0654336) to CK; a grant from the DOE Office of Biological and Environmental Research (DE-AC02-05CH11231, as part of ENIGMA, a Scientific Focus Area) to JZ; and a NASA Graduate Student Researchers Program Fellowship and a NOAA Climate and Global Change Fellowship to EA. CK would also like to thank C Hendrix and S Guenther (Center for Resources at Yellowstone National Park) for permitting assistance in Yellowstone National Park (Permit No YELL-0129). NR 49 TC 6 Z9 7 U1 5 U2 49 PU ECOLOGICAL SOC AMER PI WASHINGTON PA 1990 M STREET NW, STE 700, WASHINGTON, DC 20036 USA SN 1540-9295 EI 1540-9309 J9 FRONT ECOL ENVIRON JI Front. Ecol. Environ. PD MAY PY 2014 VL 12 IS 4 BP 224 EP 231 DI 10.1890/130055 PG 8 WC Ecology; Environmental Sciences SC Environmental Sciences & Ecology GA AG0QP UT WOS:000335120900016 ER PT J AU Thames, AD Arbid, N Sayegh, P AF Thames, April D. Arbid, Natalie Sayegh, Philip TI Cannabis use and neurocognitive functioning in a non-clinical sample of users SO ADDICTIVE BEHAVIORS LA English DT Article DE Cannabis; Cognition; Premorbid IQ; Abstinence; Past use; Abuse ID ADOLESCENT MARIJUANA USERS; ALCOHOL-USE; NEUROPSYCHOLOGICAL PERFORMANCE; EXECUTIVE FUNCTION; USE-DISORDERS; SUBSTANCE USE; YOUNG-ADULTS; DRUG-USE; BEHAVIOR; OUTCOMES AB Objective: With the recent debates over marijuana legalization and increases in use, it is critical to examine its role in cognition. While many studies generally support the adverse acute effects of cannabis on neurocognition, the non-acute effects remain less clear. The current study used a cross-sectional design to examine relationships between recent and past cannabis use on neurocognitive functioning in a non-clinical adult sample. Method: One hundred and fifty-eight participants were recruited through fliers distributed around local college campuses and the community. All participants completed the Brief Drug Use History Form, the Structured Clinical Interview for DSM-IV Disorders, and neurocognitive assessment, and underwent urine toxicology screening. Participants consisted of recent users (n = 68), past users (n = 41), and non-users (n = 49). Results: Recent users demonstrated significantly (p < .05) worse performance than non-users across cognitive domains of attention/working memory (M = 42.4, SD = 16.1 vs. M = 50.5, SD = 10.2), information processing speed (M = 44.3, SD = 7.3 vs. M = 52.1, SD = 11.0), and executive functioning (M = 43.6, SD = 13.4 vs. M = 48.6, SD = 7.2). There were no statistically significant differences between recent users and past users on neurocognitive performance. Frequency of cannabis use in the last 4 weeks was negatively associated with global neurocognitive performance and all individual cognitive domains. Similarly, amount of daily cannabis use was negatively associated with global neurocognitive performance and individual cognitive domains. Conclusions: Our results support the widespread adverse effects of cannabis use on neurocognitive functioning. Although some of these adverse effects appear to attenuate with abstinence, past users' neurocognitive functioning was consistently lower than non-users. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Thames, April D.; Sayegh, Philip] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Arbid, Natalie] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90024 USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 740 Westwood Plaza C8-226, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU National Academy of Neuropsychology; NIH/NIMH [K-23 MH095661] FX Funding for this study was provided by the National Academy of Neuropsychology. Dr. Thames is currently supported by an NIH/NIMH Career Development Award (K-23 MH095661). NAN and NIH/NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 63 TC 20 Z9 20 U1 3 U2 46 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD MAY PY 2014 VL 39 IS 5 BP 994 EP 999 DI 10.1016/j.addbeh.2014.01.019 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AG7QH UT WOS:000335612400026 PM 24556155 ER PT J AU Rosenberg, MA Maziarz, M Tan, AY Glazer, NL Zieman, SJ Kizer, JR Ix, JH Djousse, L Siscovick, DS Heckbert, SR Mukamal, KJ AF Rosenberg, Michael A. Maziarz, Marlena Tan, Alex Y. Glazer, Nicole L. Zieman, Susan J. Kizer, Jorge R. Ix, Joachim H. Djousse, Luc Siscovick, David S. Heckbert, Susan R. Mukamal, Kenneth J. TI Circulating fibrosis biomarkers and risk of atrial fibrillation: The Cardiovascular Health Study (CHS) SO AMERICAN HEART JOURNAL LA English DT Article ID GROWTH-FACTOR BETA-1; HEART-FAILURE; STRUCTURAL ABNORMALITIES; CARDIAC FIBROSIS; III PROCOLLAGEN; OLDER-ADULTS; MODEL; AGE; OVEREXPRESSION; CARDIOMYOPATHY AB Background Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited. Methods We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor beta 1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years. Results Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 mu g/L), adjusted hazard ratios (95% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor beta 1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk. Conclusion In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship. C1 [Rosenberg, Michael A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Cardiac Electrophysiol, Boston, MA USA. [Rosenberg, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Maziarz, Marlena] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Tan, Alex Y.] Virginia Commonwealth Univ, Div Electrophysiol, Richmond, VA USA. [Glazer, Nicole L.] Merck Pharmaceut, Translat & Hlth Informat, Boston, MA USA. [Zieman, Susan J.] NIA, Dept Med, Div Cardiol, Johns Hopkins Med Inst, Baltimore, MD 21224 USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. [Djousse, Luc] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Mukamal, Kenneth J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Mukamal, Kenneth J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. RP Rosenberg, MA (reprint author), 1400 VFW Pkwy,111CA, Boston, MA 02132 USA. EM Michael.rosenberg@va.gov RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [U01 HL080295, HHSN268200800007C, HHSN268201200036C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 HL080295]; NIA NIH HHS [R01 AG023629, R56 AG023629] NR 45 TC 8 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 BP 723 EP U114 AR 723-728.e2 DI 10.1016/j.ahj.2014.01.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800013 PM 24766983 ER PT J AU Ho, JE Yin, XY Levy, D Vasan, RS Magnani, JW Ellinor, PT McManus, DD Lubitz, SA Larson, MG Benjamin, EJ AF Ho, Jennifer E. Yin, Xiaoyan Levy, Daniel Vasan, Ramachandran S. Magnani, Jared W. Ellinor, Patrick T. McManus, David D. Lubitz, Steven A. Larson, Martin G. Benjamin, Emelia J. TI Galectin 3 and incident atrial fibrillation in the community SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; PREDICTING STROKE; FIBROSIS; FRAMINGHAM; DYSFUNCTION; MARKER; RISK; OVEREXPRESSION; EPIDEMIOLOGY; MACROPHAGES AB Background Galectin 3 (Gal-3) is a potential mediator of cardiac fibrosis, and Gal-3 concentrations predict incident heart failure. The same mechanisms that lead to cardiac fibrosis in heart failure may influence development of atrial fibrosis and atrial fibrillation (AF). We examined the association of Gal-3 and incident AF in the community. Methods Plasma Gal-3 concentrations were measured in 3,306 participants of the Framingham Offspring cohort who attended the sixth examination cycle (1995-1998, mean age 58 years, 54% women). Cox proportional hazards regression models were used to assess the association of baseline Gal-3 concentrations and incident AF. Results Over a median follow-up period of 10 years, 250 participants developed incident AF. Crude incidence rates of AF by increasing sex-specific Gal-3 quartiles were 3.7%, 5.9%, 9.1%, and 11.5% (log-rank test P < .0001). In age-and sex-adjusted analyses, each 1-SD increase in log(e)-Gal-3 was associated with a 19% increased hazard of incident AF (hazard ratio 1.19, 95% CI 1.05-1.36, P = .009). This association was not significant after adjustment for traditional clinical AF risk factors (hazard ratio 1.12, 95% CI 0.98-1.28, P = .10). Conclusion Higher circulating Gal-3 concentrations were associated with increased risk of developing AF over the subsequent 10 years in age-and sex-adjusted analyses but not after accounting for other traditional clinical AF risk factors. Our results do not support a role for Gal-3 in AF risk prediction. Further studies are needed to evaluate whether Gal-3 plays a role in the development of AF substrate similar to HF. C1 [Ho, Jennifer E.; Yin, Xiaoyan; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Ho, Jennifer E.; Yin, Xiaoyan; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Magnani, Jared W.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02459 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02459 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02459 USA. [Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02459 USA. RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02459 USA. EM jenho@bu.edu OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [KL2 RR031981]; NHLBI NIH HHS [K23 HL116780, K24 HL105780, N01 HC025195, R01 HL092577, R01 HL102214, RC1 HL101056, U01 HL105268]; NINDS NIH HHS [R01 NS017950] NR 38 TC 27 Z9 28 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 BP 729 EP U121 AR 729-734.e1 DI 10.1016/j.ahj.2014.02.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800014 PM 24766984 ER PT J AU Lu, LY Krumholz, HM Tu, JV Ross, JS Ko, DT Jackevicius, CA AF Lu, Lingyun Krumholz, Harlan M. Tu, Jack V. Ross, Joseph S. Ko, Dennis T. Jackevicius, Cynthia A. TI Impact of the ENHANCE Trial on the use of ezetimibe in the United States and Canada SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIOVASCULAR-DISEASE; SIMVASTATIN; PREVENTION; THERAPY; RECOMMENDATIONS; DYSLIPIDEMIA; PUBLICATION; DIAGNOSIS; OUTCOMES; ONTARIO AB Background We previously found that the use of ezetimibe increased rapidly with different patterns between the United States (US) and Canada prior to the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhance Atherosclerosis Regression (ENHANCE) trial, which was reported in January 2008, and failed to show that the drug slowed the progression of atherosclerosis. What is not known is how practice in the 2 countries changed after the ENHANCE trial. We examined ezetimibe use trends in the US and Canada before and after the reporting of the ENHANCE trial. Methods We conducted a population-based, retrospective, time-series analysis using the data collected by IMS Health in the US and CompuScript in Canada from January 1, 2002, to December 31, 2009. The main outcome measure was monthly number of prescriptions for ezetimibe-containing products. Results The monthly number of ezetimibe prescriptions/100,000 population rose from 6 to 1,082 in the US from November 2002 to January 2008, then significantly declined to 572/100,000 population by December 2009 after the release of the ENHANCE trial, a decrease of 47.1% (P < .001). In contrast, in Canada, use continuously rose from 2 to 495/100,000 population from June 2003 to December 2009 (P = .2). United States expenditures totaled $2.24 billion in 2009. Conclusions Ezetimibe remains commonly used in both the US and Canada. Ezetimibe use has decreased in the US post-ENHANCE, whereas use has gradually but steadily increased in Canada. The diverging patterns of ezetimibe use in the US and Canada require further investigation, as they reveal that a common evidence base is eliciting very different utilization patterns in neighboring countries. C1 [Lu, Lingyun; Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA. [Lu, Lingyun; Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Krumholz, Harlan M.] Yale Univ, Dept Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Krumholz, Harlan M.; Ross, Joseph S.] Yale Univ, Yale New Haven Hosp, Sch Med, Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06520 USA. [Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Tu, Jack V.; Ko, Dennis T.; Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Tu, Jack V.; Ko, Dennis T.; Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Tu, Jack V.; Ko, Dennis T.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada. [Ross, Joseph S.] Yale Univ, Dept Med, Gen Internal Med Sect, New Haven, CT 06520 USA. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E Second St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu FU College of Pharmacy of Western University of Health Sciences, Pomona, CA; Canadian Institutes of Health Research; National Heart, Lung, and Blood Institute [U01-HL105270]; Heart and Stroke Foundation of Ontario, Toronto, Ontario; National Institute on Aging [K08 AG032886]; American Federation of Aging Research through the Paul B. Beeson Career Development Award Program; Heart and Stroke Foundation of Ontario; Ontario Ministry of Health and Long-Term Care, Toronto, Ontario FX This study was funded in part by the College of Pharmacy of Western University of Health Sciences, Pomona, CA, and in part by a Canadian Institutes of Health Research team grant in cardiovascular outcomes research to the Canadian Cardiovascular Outcomes Research Team. Neither funding source had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Dr Krumholz is chair of a cardiac scientific advisory board for UnitedHealth and supported by grant U01-HL105270 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute. Drs Krumholz and Ross receive support from Medtronic, Inc, to develop methods of clinical trial data sharing; from the Centers of Medicare and Medicaid Services to develop and maintain performance measures that are used for public reporting; and from the Food and Drug Administration to develop methods for postmarket surveillance of medical devices. Dr Tu is supported by a Canada Research Chair in Health Services Research and by a Career Investigator award of the Heart and Stroke Foundation of Ontario, Toronto, Ontario. Dr Ross is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. Dr Ko is supported by a Clinician Scientist (Phase II) Award from the Heart and Stroke Foundation of Ontario. The Institute for Clinical Evaluative Sciences is supported by an operating grant from the Ontario Ministry of Health and Long-Term Care, Toronto, Ontario. NR 30 TC 10 Z9 10 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 AR 683 DI 10.1016/j.ahj.2014.01.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800008 PM 24766978 ER PT J AU Mangalmurti, S Seabury, SA Chandra, A Lakdawalla, D Oetgen, WJ Jena, AB AF Mangalmurti, Sandeep Seabury, Seth A. Chandra, Amitabh Lakdawalla, Darius Oetgen, William J. Jena, Anupam B. TI Medical professional liability risk among US cardiologists SO AMERICAN HEART JOURNAL LA English DT Article ID MALPRACTICE LITIGATION; PHYSICIANS; CLAIMS; SYSTEM; COSTS AB Background Medical professional liability (MPL) remains a significant burden for physicians, in general, and cardiologists, in particular, as recent research has shown that average MPL defense costs are higher in cardiology than other specialties. Knowledge of the clinical characteristics and outcomes of lawsuits against cardiologists may improve quality of care and risk management. Methods We analyzed closed MPL claims of 40,916 physicians and 781 cardiologists insured by a large nationwide insurer for >= 1 policy year between 1991 and 2005. Results The annual percentage of cardiologists facing an MPL claim was 8.6%, compared with 7.4% among physicians overall (P < .01). Among 530 claims, 72 (13.6%) resulted in an indemnity payment, with a median size of $ 164,988. Mean defense costs for claims resulting in payment were $ 83,593 (standard deviation (s.d.) $ 72,901). The time required to close MPL claims was longer for claims with indemnity payment than claims without (29.6 versus 18.9 months; P < .001). More than half of all claims involved a patient's death (304; 57.4%), were based on inpatient care (379; 71.5%), or involved a primary cardiovascular condition (416; 78.4%). Acute coronary syndrome was the most frequent condition (234; 44.2%). Medical professional liability claims involving noncardiovascular conditions were common (66; 12.5%) and included falls or mechanical injuries had while under a cardiologist's care and a failure to diagnose cancer. Conclusions Rates of malpractice lawsuits are higher among cardiologists than physicians overall. A substantial portion of claims are noncardiovascular in nature. C1 [Mangalmurti, Sandeep] Bassett Heart Care Inst, Cooperstown, NY 13326 USA. [Seabury, Seth A.] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles, CA 90033 USA. [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Chandra, Amitabh] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. [Lakdawalla, Darius] Univ So Calif, Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Lakdawalla, Darius] Univ So Calif, Sch Policy Planning & Dev, Los Angeles, CA USA. [Oetgen, William J.] Amer Coll Cardiol, Div Sci & Qual, Washington, DC USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mangalmurti, S (reprint author), Bassett Heart Care Inst, One Atwell Rd, Cooperstown, NY 13326 USA. EM sandeep.mangalmurti@bassett.org OI Lakdawalla, Darius/0000-0001-5934-8042 FU NIA NIH HHS [5P30AG024968, 7R01AG031544, P01 AG019783, P01 AG19783-02, P30 AG024968]; NIH HHS [DP5 OD017897, 1DP5OD017897-01] NR 18 TC 6 Z9 6 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 AR 690 DI 10.1016/j.ahj.2014.02.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800009 PM 24766979 ER PT J AU Ordulu, Z Wong, KE Currall, BB Iyanov, AR Pereira, S Althari, S Gusella, JF Talkowski, ME Morton, CC AF Ordulu, Zehra Wong, Kristen E. Currall, Benjamin B. Iyanov, Andrew R. Pereira, Shahrin Althari, Sara Gusella, James F. Talkowski, Michael E. Morton, Cynthia C. TI Describing Sequencing Results of Structural Chromosome Rearrangements with a Suggested Next-Generation Cytogenetic Nomenclature SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN GENOME; MICROARRAY ANALYSIS; MEDICAL GENETICS; AMERICAN-COLLEGE; DATABASE; CANCER; ABNORMALITIES; STANDARDS; TRANSLOCATION; DISRUPTION AB With recent rapid advances in genomic technologies, precise delineation of structural chromosome rearrangements at the nucleotide level is becoming increasingly feasible. In this era of "next-generation cytogenetics" (i.e., an integration of traditional cytogenetic techniques and next-generation sequencing), a consensus nomenclature is essential for accurate communication and data sharing. Currently, nomenclature for describing the sequencing data of these aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic Nomenclature, which is concordant with the International System for Human Cytogenetic Nomenclature (2013). This system starts with the alignment of rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a concise and detailed description of chromosomal changes. To facilitate usage and implementation of this nomenclature, we are developing a program designated BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of which is accessible online. A standardized characterization of structural chromosomal rearrangements is essential both for research analyses and for application in the clinical setting. C1 [Ordulu, Zehra; Wong, Kristen E.; Currall, Benjamin B.; Iyanov, Andrew R.; Pereira, Shahrin; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Althari, Sara; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. EM cmorton@partners.org FU NIH [GM061354, HD060530, HD065286, MH087123, MH095867]; Simons Foundation for Autism Research; Nancy Lurie Marks Family Foundation; [F32 DC012466]; [T32 GM007748] FX We are grateful to all participating subjects and families and to the many healthcare professionals who have contributed to the Developmental Genome Anatomy Project. We especially thank Ye Cao, Richard Choy, Cary Scott Gallagher, Anne Giersch, Anita Hawkins, Linda Johnson, Nahid Robertson, and Jun Shen for their contributions during manuscript preparation. This work was supported by NIH grants (GM061354 to C.C.M. and J.F.G., HD060530 to C.C.M., HD065286 to J.F.G., and MH087123 and MH095867 to M.E.T.). B.B.C. is supported by F32 DC012466 and previously by T32 GM007748. M.E.T. and J.F.G. are supported by the Simons Foundation for Autism Research and the Nancy Lurie Marks Family Foundation. NR 44 TC 16 Z9 16 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 1 PY 2014 VL 94 IS 5 BP 695 EP 709 DI 10.1016/j.ajhg.2014.03.020 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AG5VB UT WOS:000335485700004 PM 24746958 ER PT J AU Wang, SR Agarwala, V Flannick, J Chiang, CWK Altshuler, D Hirschhorn, JN AF Wang, Sophie R. Agarwala, Vineeta Flannick, Jason Chiang, Charleston W. K. Altshuler, David Hirschhorn, Joel N. CA GoT2D Consortium TI Simulation of Finnish Population History, Guided by Empirical Genetic Data, to Assess Power of Rare-Variant Tests in Finland SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COMPLEX TRAITS; LINKAGE DISEQUILIBRIUM; SEQUENCING DATA; DISEASE; ARCHITECTURE; MUTATION; NUCLEOTIDE; DNA; DISCOVERY AB Finnish samples have been extensively utilized in studying single-gene disorders, where the founder effect has clearly aided in discovery, and more recently in genome-wide association studies of complex traits, where the founder effect has had less obvious impacts. As the field starts to explore rare variants' contribution to polygenic traits, it is of great importance to characterize and confirm the Finnish founder effect in sequencing data and to assess its implications for rare-variant association studies. Here, we employ forward simulation, guided by empirical deep resequencing data, to model the genetic architecture of quantitative polygenic traits in both the general European and the Finnish populations simultaneously. We demonstrate that power of rare-variant association tests is higher in the Finnish population, especially when variants' phenotypic effects are tightly coupled with fitness effects and therefore reflect a greater contribution of rarer variants. SKAT-O, variable-threshold tests, and single-variant tests are more powerful than other rare-variant methods in the Finnish population across a range of genetic models. We also compare the relative power and efficiency of exome array genotyping to those of high-coverage exome sequencing. At a fixed cost, less expensive genotyping strategies have far greater power than sequencing; in a fixed number of samples, however, genotyping arrays miss a substantial portion of genetic signals detected in sequencing, even in the Finnish founder population. As genetic studies probe sequence variation at greater depth in more diverse populations, our simulation approach provides a framework for evaluating various study designs for gene discovery. C1 [Wang, Sophie R.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Wang, Sophie R.; Agarwala, Vineeta; Flannick, Jason; Altshuler, David; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Wang, Sophie R.; Altshuler, David; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Agarwala, Vineeta] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Agarwala, Vineeta] Harvard Univ, Program Biophys, Grad Sch Arts & Sci, Cambridge, MA 02138 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Chiang, Charleston W. K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Hirschhorn, JN (reprint author), Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. EM joelh@broadinstitute.org RI Meisinger, Christine/B-5358-2014; Meitinger, Thomas/O-1318-2015; Hrabe de Angelis, Martin/F-5531-2012; OI Hrabe de Angelis, Martin/0000-0002-7898-2353; Wang, Sophie Ran/0000-0002-7897-8389; Fuchsberger, Christian/0000-0002-5918-8947; Kumar, Ashish/0000-0002-7075-5930; van de Bunt, Martijn/0000-0002-6744-6125; Chiang, Charleston/0000-0002-0668-7865; Tuomi, Tiinamaija/0000-0002-8306-6202; Hattersley, Andrew/0000-0001-5620-473X; Locke, Adam/0000-0001-6227-198X FU NIH [2R01DK075787, T32GM007753, T32GM008313, T32GM007748-33]; Pfizer; NIH National Research Service Award Postdoctoral Fellowship [F32GM106656]; National Institute of Diabetes and Digestive and Kidney Diseases [1RC2DK088389-01] FX We gratefully acknowledge B. Lambert and K. Weiss (authors of the simulation tool ForSim) for helpful technical assistance. Without their software, this work would not have been possible. We also thank M. McCarthy and M. Boehnke for discussion and insightful critiques and M. Lin for helping with the preparation of figures. This work was supported by NIH grant 2R01DK075787 to J.N.H. and NIH training grants T32GM007753 and T32GM008313 to V.A. and T32GM007748-33 to J.F. (who also received funding from Pfizer). C.W.K.C. is supported by NIH National Research Service Award Postdoctoral Fellowship F32GM106656. The Genetics of Type 2 Diabetes Study is supported by grant 1RC2DK088389-01 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 35 TC 6 Z9 6 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 1 PY 2014 VL 94 IS 5 BP 710 EP 720 DI 10.1016/j.ajhg.2014.03.019 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AG5VB UT WOS:000335485700005 PM 24768551 ER PT J AU Sergouniotis, PI Chakarova, C Murphy, C Becker, M Lenassi, E Arno, G Lek, M MacArthur, DG Bhattacharya, SS Moore, AT Holder, GE Robson, AG Wolfrum, U Webster, AR Plagnol, V AF Sergouniotis, Panagiotis I. Chakarova, Christina Murphy, Cian Becker, Mirjana Lenassi, Eva Arno, Gavin Lek, Monkol MacArthur, Daniel G. Bhattacharya, Shomi S. Moore, Anthony T. Holder, Graham E. Robson, Anthony G. Wolfrum, Uwe Webster, Andrew R. Plagnol, Vincent CA UCL-Exomes Consortium TI Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DNA-SEQUENCING DATA; GLUCOCORTICOID-RECEPTOR; PROTEIN; CILIA; POLYGLUTAMYLATION; GENE; DEGENERATION; CILIOPATHIES; ASSOCIATION; MECHANISMS AB In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with "cone-first" retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TILLS, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs(star)2];[Glu529Valfs(star)2], and c.[401delT(;) 3354G>A], p.[Leu134Argfs(star)45(;)Trp1118(star)]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543(star)) in TILLS. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TILLS mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TILLS has been previously reported to be essential for the correct function of sperm flagella-in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families. C1 [Sergouniotis, Panagiotis I.; Chakarova, Christina; Lenassi, Eva; Arno, Gavin; Bhattacharya, Shomi S.; Moore, Anthony T.; Holder, Graham E.; Robson, Anthony G.; Webster, Andrew R.] UCL Inst Ophthalmol, London EC1V 9EL, England. [Sergouniotis, Panagiotis I.; Lenassi, Eva; Moore, Anthony T.; Holder, Graham E.; Robson, Anthony G.; Webster, Andrew R.] Moorfields Eye Hosp, London EC1V 2PD, England. [Murphy, Cian; Plagnol, Vincent] UCL Genet Inst, London WC1E 6BT, England. [Becker, Mirjana; Wolfrum, Uwe] Johannes Gutenberg Univ Mainz, Inst Zool, Focus Program Translat Neurosci, D-55099 Mainz, Germany. [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Webster, AR (reprint author), UCL Inst Ophthalmol, London EC1V 9EL, England. EM andrew.webster@ucl.ac.uk OI Sergouniotis, Panos/0000-0003-0986-4123; Plagnol, Vincent/0000-0002-5597-9215 FU Macular Society UK; UK National Institute for Health Research (Biomedical Research Centre); RP Fighting Blindness; Fight for Sight (including the Mercer Fund); US Foundation Fighting Blindness; UK Medical Research Council; Wellcome Trust; German Ministry of Education and Research ("HOPE2"); FAUN-Stiftung; European Commission [EC FP7/2009/241955]; NIH National Institute of General Medical Sciences [1R01GM104371]; UK National Institute for Health Research (Moorfields Eye Hospital); UK National Institute for Health Research (Institute of Ophthalmology) FX We acknowledge the cooperation and help provided by the family members in this study. We are grateful to colleagues who referred affected individuals to us at Moorfields Eye Hospital and to those who contributed to the assembly of the cone-rod and macular dystrophy panel, particularly Kaoru Fujinami, Alice Davidson, Alan Bird, Michel Michaelides, Genevieve Wright, Sophie Devery, Ravinder Chana, Beverley Scott, and Naushin Waseem. We thank our colleagues from the cornea bank of the Department of Ophthalmology at Johannes Gutenberg University Mainz for providing the human donor eye and our colleagues at University College London for kindly contributing to the UCL-exomes Control panel. We acknowledge the following sources of funding: Macular Society UK (www.maculardisease.org), the UK National Institute for Health Research (Biomedical Research Centre, Moorfields Eye Hospital, and Institute of Ophthalmology), RP Fighting Blindness, Fight for Sight (including the Mercer Fund), the US Foundation Fighting Blindness; the UK Medical Research Council, the Wellcome Trust, the German Ministry of Education and Research ("HOPE2"), FAUN-Stiftung, and the European Commission Seventh Framework Program (EC FP7/2009/241955, SYSCILIA). D.G.M. and M.L. were funded by the NIH National Institute of General Medical Sciences under award 1R01GM104371. NR 38 TC 16 Z9 17 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 1 PY 2014 VL 94 IS 5 BP 760 EP 769 DI 10.1016/j.ajhg.2014.04.003 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AG5VB UT WOS:000335485700010 PM 24791901 ER PT J AU Christov, M Corbin, B Maeda, A Gardella, TJ Juppner, H AF Christov, Marta Corbin, Braden Maeda, Akira Gardella, Thomas J. Jueppner, Harald TI USE OF PTH TO LOWER PHOSPHORUS AND FGF23 IN CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF) CY APR 22-26, 2014 CL Las Vegas, NV SP Natl Kidney Fdn C1 [Christov, Marta; Corbin, Braden; Maeda, Akira; Gardella, Thomas J.; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 MA 86 BP A40 EP A40 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600088 ER PT J AU Hernandez, J Tarbox, L Anstead, G Dyer, C AF Hernandez, Judith Tarbox, Lauren Anstead, Gregory Dyer, Christopher TI TENOFOVIR RELATED ACUTE INTERSTITIAL NEPHRITIS: A CASE SERIES SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF) CY APR 22-26, 2014 CL Las Vegas, NV SP Natl Kidney Fdn C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 MA 147 BP A55 EP A55 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600149 ER PT J AU Khawaja, Z AF Khawaja, Zeeshan TI CHRONIC ANTIBODY MEDIATED REJECTION: C1q FIXATION BY DSA CORRELATES WITH C4d DEPOSITION IN THE GRAFT AND MORE SEVERE PATHOLOGY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF) CY APR 22-26, 2014 CL Las Vegas, NV SP Natl Kidney Fdn C1 [Khawaja, Zeeshan] Lahey Clin Fdn, Dept Transplantat, Burlington, MA USA. [Khawaja, Zeeshan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 MA 198 BP A68 EP A68 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600200 ER PT J AU Nassar, T Tarbox, L Hernandez, J Dyer, C AF Nassar, Tareq Tarbox, Lauren Hernandez, Judith Dyer, Christopher TI PHYSICAL ACTIVITY AMONGST VETERANS WITH ESRD: PERCEPTIONS AND BARRIERS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF) CY APR 22-26, 2014 CL Las Vegas, NV SP Natl Kidney Fdn C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 MA 251 BP A81 EP A81 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600253 ER PT J AU Rohatgi, R Gentile, D Cancel-Santiago, R Gharitza, R Rindt, J Post, J He, JC Malina, J Langhoff, E AF Rohatgi, Rajeev Gentile, Denise Cancel-Santiago, Rosemarie Gharitza, Retha Rindt, John Post, James He, John Cijiang Malina, Joanne Langhoff, Erik TI TELENEPHROLOGY: A MODEL OF PATIENT CENTERED CARE SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF) CY APR 22-26, 2014 CL Las Vegas, NV SP Natl Kidney Fdn C1 James J Peters VAMC, Bronx, NY USA. Hudson Valley VAMC, Castle Point, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 MA 307 BP A95 EP A95 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600309 ER PT J AU Creanga, AA Bateman, BT Kuklina, EV Callaghan, WM AF Creanga, Andreea A. Bateman, Brian T. Kuklina, Elena V. Callaghan, William M. TI Racial and ethnic disparities in severe maternal morbidity: a multistate analysis, 2008-2010 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ethnicity; race; severe maternal morbidity ID PREGNANCY-RELATED MORTALITY; UNITED-STATES; DELIVERY; FETAL; HOSPITALIZATIONS; PREVALENCE; INFANTS; RACE AB OBJECTIVE: The purpose of this study was to examine racial and ethnic disparities in severe maternal morbidity during delivery hospitalizations in the United States. STUDY DESIGN: We identified delivery hospitalizations from 20082010 in State Inpatient Databases from 7 states. We used International Classification of Diseases, 9th Revision, codes to create severe maternal morbidity indicators during delivery hospitalizations. We calculated the rates of severe maternal morbidity that were measured with and without blood transfusion for 5 racial/ethnic groups: non-Hispanic white, non-Hispanic black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women. Poisson regression models were fitted to explore the associations between race/ethnicity and severe maternal morbidity after we controlled for potential confounders. RESULTS: Overall, severe maternal morbidity rates that were measured with and without blood transfusion were 150.7 and 64.3 per 10,000 delivery hospitalizations, respectively. Non-Hispanic black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women had 2.1, 1.3, 1.2, and 1.7 times (all P < .05), respectively, higher rates of severe morbidity that were measured with blood transfusion compared with non-Hispanic white women; similar increased rates were observed when severe morbidity was measured without blood transfusion. Other significant positive predictors of severe morbidity were age <20 and >= 30 years, self-pay or Medicaid coverage for delivery, low socioeconomic status, and presence of chronic medical conditions. CONCLUSION: Severe maternal morbidity disproportionally affects racial/ ethnic minority women, especially non-Hispanic black women. There is a need for a systematic review of severe maternal morbidities at the facility, state, and national levels to guide the development of quality improvement interventions to reduce the racial/ ethnic disparities in severe maternal morbidity. C1 [Creanga, Andreea A.; Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. RP Creanga, AA (reprint author), Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, 4770 Buford Hwy NE,Mail Stop K-23, Atlanta, GA 30341 USA. EM acreanga@cdc.gov NR 24 TC 10 Z9 12 U1 2 U2 5 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 MAY PY 2014 VL 210 IS 5 AR 435.e1 DI 10.1016/j.ajog.2013.11.039 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700011 PM 24295922 ER PT J AU Wu, E Kaimal, AJ Houston, K Yee, LM Nakagawa, S Kuppermann, M AF Wu, Erica Kaimal, Anjali J. Houston, Kathryn Yee, Lynn M. Nakagawa, Sanae Kuppermann, Miriam TI Strength of preference for vaginal birth as a predictor of delivery mode among women who attempt a vaginal delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE delivery mode; patient preferences ID CESAREAN DELIVERY; DECISION-MAKING; PROVIDER PREFERENCES; FOLLOW-UP; SECTION; PATIENT; CHILDBIRTH; MANAGEMENT; PREGNANCY AB OBJECTIVE: We sought to assess the relationship between strength of preference for vaginal birth and likelihood of vaginal delivery among women attempting this delivery mode. STUDY DESIGN: We conducted a longitudinal study of mode of delivery preferences among women who were <36 weeks' pregnant. Participants completed a sociodemographic and clinical questionnaire and were asked if they preferred vaginal or cesarean delivery. Participants who preferred vaginal delivery completed a standard gamble exercise to assess the strength of this preference on a 0-to-1 scale (higher scores indicate stronger preference for vaginal delivery); those preferring cesarean delivery were assigned a value of 0. Data on clinical characteristics and delivery mode were obtained via telephone interview or chart review. Logistic regression was used to identify predictors of delivery mode among women who attempted a vaginal delivery. RESULTS: Of 210 participants, 156 attempted a vaginal delivery. Their mean and median vaginal delivery preference scores were 0.70 (SD 0.31) and 0.75 (interquartile range, 0.50-0.99), respectively. In multivariate analyses, women with a prior cesarean delivery (adjusted odds ratio [aOR], 0.08; 95% confidence interval [CI], 0.02-0.39) or who delivered an infant >= 4000 g (aOR, 0.04; 95% CI, 0.01-0.28) had significantly lower odds of having a vaginal delivery. After controlling for potential confounders, participants with a stronger preference for vaginal delivery were at significantly higher odds of having a vaginal delivery (aOR, 1.54; 95% CI, 1.01-2.34 for every 0.2 increase on the 0-to-1 scale). CONCLUSION: Among women who attempt a vaginal delivery, the strength of preference for vaginal birth is predictive of the delivery mode ultimately undergone. C1 [Wu, Erica] Univ Calif Irvine, Sch Med, Dept Obstet & Gynecol, Orange, CA 92668 USA. [Kaimal, Anjali J.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Houston, Kathryn; Nakagawa, Sanae; Kuppermann, Miriam] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Kuppermann, Miriam] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Yee, Lynn M.] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. RP Wu, E (reprint author), Univ Calif Irvine, Sch Med, Dept Obstet & Gynecol, Orange, CA 92668 USA. FU National Center for Research Resources; National Center for Advancing Translational Sciences; National Institutes of Health, through the University of California, San Francisco; Clinical & Translational Science Institute [UL1 RR024131]; University of California, San Francisco, Clinical & Translational Science Institute [UL1 TR000004] FX This project was supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through the University of California, San Francisco, Clinical & Translational Science Institute, grant number UL1 RR024131 and the University of California, San Francisco, Clinical & Translational Science Institute, grant number UL1 TR000004. NR 32 TC 4 Z9 4 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 MAY PY 2014 VL 210 IS 5 AR 440.e1 DI 10.1016/j.ajog.2013.11.021 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700013 PM 24246523 ER PT J AU Young, BC Stanic, AK Panda, B Rueda, BR Panda, A AF Young, Brett C. Stanic, Aleksandar K. Panda, Britta Rueda, Bo R. Panda, Alexander TI Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE dendritic cells; innate immune system; pregnancy; toll-like receptors ID FETAL DNA; TROPHOBLAST CELLS; CESAREAN-SECTION; MATERNAL PLASMA; PREECLAMPSIA; ACTIVATION; LABOR; TERM; RECOGNITION; RESPONSES AB OBJECTIVE: Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. STUDY DESIGN: This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. RESULTS: TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. CONCLUSION: Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies. C1 [Young, Brett C.; Stanic, Aleksandar K.; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Panda, Britta] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. [Panda, Alexander] Yale Univ, Sch Med, Dept Med, Div Pulm Crit Care & Sleep Med, New Haven, CT 06510 USA. RP Young, BC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. OI Stanic-Kostic, Aleksandar/0000-0003-1946-6436 FU Vincent Memorial Research Funds FX This research received financial support from Vincent Memorial Research Funds (BRR). NR 26 TC 1 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 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2014 VL 210 IS 5 AR 445.e1 DI 10.1016/j.ajog.2013.11.037 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700015 PM 24291497 ER PT J AU Wong, RM Ianculescu, I Sharma, S Gage, DL Olevsky, OM Kotova, S Kostic, MN Grundfest, WS Hou, DM Cameron, RB AF Wong, Raymond M. Ianculescu, Irina Sharma, Sherven Gage, Diana L. Olevsky, Olga M. Kotova, Svetlana Kostic, Marko N. Grundfest, Warren S. Hou, Dongmei Cameron, Robert B. TI Immunotherapy for Malignant Pleural Mesothelioma Current Status and Future Prospects SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Review DE mesothelioma; immunotherapy; immunosuppression; multimodality ID T-REGULATORY CELLS; BETA GENE-TRANSFER; IMMUNE-RESPONSES; SURGICAL DEBULKING; ANTI-PD-1 ANTIBODY; ADVANCED MELANOMA; INTERFERON-BETA; TUMOR-CELLS; GM-CSF; THERAPY AB Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resistant to conventional therapies. Immunotherapy is a promising investigational approach for MPM that has shown some evidence of clinical benefit in select patients. However, tumor-induced immunosuppression is likely a major impediment to achieving optimal clinical responses to immunotherapeutic intervention. MPM contains a variable degree of infiltrating T-regulatory cells and M2 macrophages, which are believed to facilitate tumor evasion from the host immune system. Additional immunosuppressive factors identified in other human tumor types, such as tumor-associated programmed death ligand-1 expression, may be relevant for investigation in MPM. Conventional cytoreductive therapies, such as radiation, chemotherapy, and surgery, may play a critical role in successful immunotherapeutic strategies by ablating intratumoral and/or systemic immunosuppressive factors, thus creating a host environment more amenable to immunotherapy. This article reviews the immunotherapeutic approachesbeing evaluated in patientswithMPM and discusses howimmunotherapymight be rationally combinedwith conventional tumor cytoreductive therapies for this disease. C1 [Wong, Raymond M.; Ianculescu, Irina] Pacific Heart Lung & Blood Inst, Pacific Meso Ctr, Los Angeles, CA 90025 USA. [Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med Pulm & Crit Care, Los Angeles, CA USA. [Gage, Diana L.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Radiat Oncol, Los Angeles, CA USA. [Kotova, Svetlana; Cameron, Robert B.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Thorac Surg, Los Angeles, CA USA. [Olevsky, Olga M.] Univ Calif Los Angeles, Dept Hematol & Oncol, Los Angeles, CA USA. [Kostic, Marko N.; Grundfest, Warren S.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA. [Hou, Dongmei; Cameron, Robert B.] Univ Calif Los Angeles, Div Thorac Surg, Los Angeles, CA USA. [Hou, Dongmei; Cameron, Robert B.] Univ Calif Los Angeles, Comprehens Mesothelioma Program, Los Angeles, CA USA. RP Wong, RM (reprint author), Pacific Heart Lung & Blood Inst, Pacific Meso Ctr, 10780 Santa Monica Blvd 101, Los Angeles, CA 90025 USA. EM rwong@phlbi.org NR 48 TC 7 Z9 7 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2014 VL 50 IS 5 BP 870 EP 875 DI 10.1165/rcmb.2013-0472TR PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AG8DB UT WOS:000335647900009 PM 24450537 ER PT J AU Uddin, T Aktar, A Xu, P Johnson, RA Rahman, MA Leung, DT Afrin, S Akter, A Alam, MM Rahman, A Chowdhury, F Khan, AI Bhuiyan, TR Bufano, MK Rashu, R Yu, YN Wu-Freeman, Y Harris, JB LaRocque, RC Charles, RC Kovac, P Calderwood, SB Ryan, ET Qadri, F AF Uddin, Taher Aktar, Amena Xu, Peng Johnson, Russell A. Rahman, M. Arifur Leung, Daniel T. Afrin, Sadia Akter, Aklima Alam, Mohammad Murshid Rahman, Atiqur Chowdhury, Fahima Khan, Ashraful I. Bhuiyan, Taufiqur Rahman Bufano, Meagan K. Rashu, Rasheduzzaman Yu, Yanan Wu-Freeman, Ying Harris, Jason B. LaRocque, Regina C. Charles, Richelle C. Kovac, Pavol Calderwood, Stephen B. Ryan, Edward T. Qadri, Firdausi TI Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral Killed Cholera Vaccine and Comparison to Responses in Patients with Cholera SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MEMORY B-CELL; ANTIBODY-SECRETING CELL; INFECTION-DERIVED IMMUNITY; WHOLE-CELL; STRUCTURAL-ANALYSIS; HOUSEHOLD CONTACTS; CONTROLLED-TRIAL; CORE REGION; ANTIGEN; CHILDREN AB Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae 01 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection. C1 Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Uddin, Taher; Aktar, Amena; Johnson, Russell A.; Rahman, M. Arifur; Afrin, Sadia; Akter, Aklima; Alam, Mohammad Murshid; Chowdhury, Fahima; Khan, Ashraful I.; Rashu, Rasheduzzaman; Qadri, Firdausi] Icddr B, Immunol Lab, Dhaka, Bangladesh. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Harris, Jason B.; LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Bufano, Meagan K.; Rashu, Rasheduzzaman; Yu, Yanan; Wu-Freeman, Ying] Massachusetts Gen Hosp, Boston, MA 02114 USA. [LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rahman, Atiqur] Univ Dhaka, Dept Biochem & Mol Biol, Dhaka, Bangladesh. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), 68 Shaheed Tajuddin Ahmed Sharani, Dhaka 1212, Bangladesh. EM taher_imm@icddrb.org; bio_amn015@yahoo.com; xup3@mail.nih.gov; russell.a.johnson@gmail.com; marifur@icddrb.org; dleung@partners.org; sadia_afrin89@yahoo.com; aklima17@gmail.com; shafiul@icddrb.org; atique303@gmail.com; fchowdhury@icddrb.org; ashrafk@icddrb.org; MBUFANO@partners.org; rashedimm@yahoo.co; YYVAUGHN@PARTNERS.ORG; YWUFREEMAN@PARTNERS.ORG; jbharris@partners.org; RCLAROCQUE@PARTNERS.ORG; RCCHARLES@PARTNERS.ORG; Kovac@maihnh.gov; SCALDERWOOD@PARTNERS.ORG; ETRYAN@PARTNERS.ORG; fqadri@icddrb.org RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012; OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801 FU icddr,b; National Institutes of Health; NIDDK; National Institutes of Health [U01 AI058935, R03 AI063079, U01 AI077883, AI106878, K08 AI089721, K08A1100923]; Fogarty International Center; Training Grant in Vaccine Development and Public Health [TW005572]; Career Development Awards [K01 TW07409, K01 TW07144]; Fogarty International Clinical Research Scholars Award [R24 TW007988]; Swedish Sida [INT-ICDDR,B-HN-01-AV]; Howard Hughes Medical Institute; American Society for Tropical Medicine and Hygiene - Burroughs Wellcome Fund; Thrasher Research Fund Early Career Award FX This research was supported by the icddr,b, by the Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [S.B.C., E.T.R.], R03 AI063079 [F.Q.], U01 AI077883 and AI106878 [E.T.R.]), K08 AI089721 [R.C.C.], K08A1100923 [D.T.L.]) and the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [T.U., M.M.A., R.R., and F.Q.]), Career Development Awards (K01 TW07409 [J.B.H.] and K01 TW07144 [R.C.L.], and a Fogarty International Clinical Research Scholars Award (R24 TW007988 [T.U., R.A.J.]), as well as by Swedish Sida grant INT-ICDDR,B-HN-01-AV (F.Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R.C.L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene - Burroughs Wellcome Fund (D.T.L.), and a Thrasher Research Fund Early Career Award (D.T.L.). NR 49 TC 7 Z9 7 U1 1 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2014 VL 90 IS 5 BP 873 EP 881 DI 10.4269/ajtmh.13-0498 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AG8ZN UT WOS:000335707600020 PM 24686738 ER PT J AU Burris, HH Rifas-Shiman, SL Huh, SY Kleinman, K Litonjua, AA Oken, E Rich-Edwards, JW Camargo, CA Gillman, MW AF Burris, Heather H. Rifas-Shiman, Sheryl L. Huh, Susanna Y. Kleinman, Ken Litonjua, Augusto A. Oken, Emily Rich-Edwards, Janet W. Camargo, Carlos A., Jr. Gillman, Matthew W. TI Vitamin D status and hypertensive disorders in pregnancy SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Pregnancy; Preeclampsia; Hypertension; Pregnancy-induced; Vitamin D; 25-Hydroxyvitamin D ID 25-HYDROXYVITAMIN D; D DEFICIENCY; GESTATIONAL HYPERTENSION; BLOOD-PRESSURE; PREECLAMPSIA; RISK; OUTCOMES; DIET; TERM; AGE AB Purpose: Several studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25 [OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear. Methods: Among women enrolled in the Project Viva prenatal cohort in Massachusetts, we examined associations of 25(OH)D levels obtained at 16.4-36.9 weeks of gestation (mean 27.9 weeks) with hypertensive disorders of pregnancy, including preeclampsia (56/1591, 3.5%) and gestational hypertension (109/1591, 6.9%). Results: We did not detect an association between plasma 25(OH)D concentration (mean 58, standard deviation 22 nmol/L) and preeclampsia. For each 25 nmol/L increase in 25(OH)D, the adjusted odds ratio for preeclampsia was 1.14 (95% confidence interval, 0.77-1.67). By contrast and contrary to hypothesis, higher 25(OH)D concentrations were associated with higher odds of gestational hypertension: adjusted odds ratio for gestational hypertension was 1.32 (95% confidence interval, 1.01-1.72) per each 25 nmol/L increment in 25(OH)D. Vitamin D intake patterns suggest that this association was not because of reverse causation. Although the elevated hypertension risk may be due to chance, randomized trials of vitamin D supplementation during pregnancy should monitor for gestational hypertension. Conclusions: These data do not support the hypothesis that higher 25(OH)D levels lower the overall risk of hypertensive disorders of pregnancy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Burris, Heather H.] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA. [Burris, Heather H.] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. [Burris, Heather H.; Huh, Susanna Y.; Kleinman, Ken; Litonjua, Augusto A.; Oken, Emily; Rich-Edwards, Janet W.; Camargo, Carlos A., Jr.; Gillman, Matthew W.] Harvard Univ, Sch Med, Boston, MA USA. [Rifas-Shiman, Sheryl L.; Oken, Emily; Gillman, Matthew W.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med,Obes Prevent Program, Boston, MA USA. [Huh, Susanna Y.] Boston Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA USA. [Litonjua, Augusto A.; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. [Oken, Emily; Rich-Edwards, Janet W.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. [Rich-Edwards, Janet W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Burris, HH (reprint author), Beth Israel Deaconess Med Ctr, Dept Neonatol, 330 Brookline Ave,RO 318, Boston, MA 02215 USA. EM heburris@bidmc.harvard.edu OI Burris, Heather/0000-0003-4510-9547 FU National Institutes of Health [R01 HD034568, R01 HL064925, K24 HL068041, K23 ES022242, K24 HD069408]; Harvard Pilgrim Health Care Foundation; Klarman Scholars Program at Beth Israel Deaconess Medical Center FX This work was supported by the National Institutes of Health (R01 HD034568, R01 HL064925, K24 HL068041, K23 ES022242, K24 HD069408), The Harvard Pilgrim Health Care Foundation, and the Klarman Scholars Program at Beth Israel Deaconess Medical Center. NR 43 TC 14 Z9 16 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2014 VL 24 IS 5 BP 399 EP 403 DI 10.1016/j.annepidem.2014.02.001 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG9BB UT WOS:000335712500010 PM 24631523 ER PT J AU Graziani, L Jaff, MR AF Graziani, Lanfroi Jaff, Michael R. TI Drug-eluting Balloons: Are These Failed Solutions for the Treatment of Below-the-knee Peripheral Artery Disease? SO ANNALS OF VASCULAR SURGERY LA English DT Letter ID DIABETIC SUBJECTS; MAJOR AMPUTATION; INSULIN; ATHEROSCLEROSIS; MACROANGIOPATHY; CALCIFICATION; ANGIOPLASTY; ASSOCIATION C1 [Graziani, Lanfroi] Ist Clin Citta Brescia Hosp, Dept Intervent Cardiol, I-25124 Brescia, Italy. [Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Dept Vasc Med, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Sch Med, Dept Vasc Med, Boston, MA USA. RP Graziani, L (reprint author), Ist Clin Citta Brescia Hosp, Dept Intervent Cardiol, Via Gualla 15, I-25124 Brescia, Italy. EM langrazi@tin.it NR 14 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAY PY 2014 VL 28 IS 4 BP 1078 EP 1079 DI 10.1016/j.avsg.2014.02.002 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AG8GB UT WOS:000335655700069 PM 24530717 ER PT J AU George, MS Raman, R Benedek, DM Pelic, CG Grammer, GG Stokes, KT Schmidt, M Spiegel, C DeAlmeida, N Beaver, KL Borckardt, JJ Sun, XY Jain, S Stein, MB AF George, Mark S. Raman, Rema Benedek, David M. Pelic, Christopher G. Grammer, Geoffrey G. Stokes, Karen T. Schmidt, Matthew Spiegel, Chad DeAlmeida, Nancy Beaver, Kathryn L. Borckardt, Jeffrey J. Sun, Xiaoying Jain, Sonia Stein, Murray B. TI A Two-site Pilot Randomized 3 Day Trial of High Dose Left Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for Suicidal Inpatients SO BRAIN STIMULATION LA English DT Article DE TMS; Transcranial; Suicide; Prefrontal; Magnetic ID LEARNED HELPLESSNESS; RESISTANT DEPRESSION; BEHAVIORAL-CONTROL; MOTOR THRESHOLD; HEALTHY-ADULTS; PAIN; CORTEX; LITHIUM; PERCEPTION; PREVENTION AB Background: Suicide attempts and completed suicides are common, yet there are no proven acute medication or device treatments for treating a suicidal crisis. Repeated daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4-6 weeks is a new FDA-approved treatment for acute depression. Some open-label rTMS studies have found rapid reductions in suicidality. Design: This study tests whether a high dose of rTMS to suicidal inpatients is feasible and safe, and also whether this higher dosing might rapidly improve suicidal thinking. This prospective, 2-site, randomized, active sham-controlled (1: 1 randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality treatment. The setting was two inpatient military hospital wards (one VA, the other DOD). Patients: Research staff screened approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis. Because of the funding source, all patients also had either post-traumatic stress disorder, mild traumatic brain injury, or both. TMS methods: Repetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total 9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal insert blocking the magnetic field and utilized electrodes on the scalp, which delivered a matched somatosensory sensation. Main outcome measure: Primary outcomes were the daily change in severity of suicidal thinking as measured by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily, as well as subjective visual analog scale measures before and after each TMS session. Mixed model repeated measures (MMRM) analysis was performed on modified intent to treat (mITT) and completer populations. Results: This intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side effects occurred, none differing by arm, and the 3-day retention rate was 88%. No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores declined rapidly over the 3 days for both groups (sham change -15.3 points, active change -15.4 points), with a trend for more rapid decline on the first day with active rTMS (sham change -6.4 points, active -10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change -5.9 (95% CI: -10.1, -1.7), active -13 points (95% CI: -18.7, -7.4); P = 0.054]. Subjective ratings of 'being bothered by thoughts of suicide' declined non- significantly more with active rTMS than with sham at the end of 9 sessions of treatment in the mITT analysis [sham change 31.9 (95% CI: 41.7, 22.0), active change 42.5 (95% CI: 53.8, 31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change -24.9 (95% CI: -34.4, -15.3), active change -43.8 (95% CI: -57.2, -30.3); P = 0.028]. Conclusions: Delivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is possible and safe, with few side effects and no worsening of suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue Scale data over the 3 days) need to be tested for replication in a larger sample. (C) 2014 Elsevier Inc. All rights reserved. C1 [George, Mark S.; Pelic, Christopher G.; Schmidt, Matthew; Beaver, Kathryn L.; Borckardt, Jeffrey J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [George, Mark S.; Pelic, Christopher G.; Schmidt, Matthew; Beaver, Kathryn L.; Borckardt, Jeffrey J.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Div, Charleston, SC 29425 USA. [Benedek, David M.; Grammer, Geoffrey G.; Spiegel, Chad; DeAlmeida, Nancy] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Raman, Rema; Stokes, Karen T.; Sun, Xiaoying; Jain, Sonia; Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP George, MS (reprint author), MUSC, IOP, 502 N,67 President St, Charleston, SC 29425 USA. EM georgem@musc.edu FU U.S. Army Medical Research and Materiel Command (USAMRMC); DOD INTRuST [W81XWH-08-2-0159] FX Funded by U.S. Army Medical Research and Materiel Command (USAMRMC).; Funding mechanism: Contract # W81XWH-08-2-0159, DOD INTRuST. NR 59 TC 16 Z9 18 U1 6 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2014 VL 7 IS 3 BP 421 EP 431 DI 10.1016/j.brs.2014.03.006 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG9KZ UT WOS:000335739400012 PM 24731434 ER PT J AU Chahine, G Short, B Spicer, K Schmidt, M Burns, C Atoui, M George, MS Sackeim, HA Nahas, Z AF Chahine, George Short, Baron Spicer, Ken Schmidt, Matthew Burns, Carol Atoui, Mia George, Mark S. Sackeim, Harold A. Nahas, Ziad TI Regional Cerebral Blood Flow Changes Associated With Focal Electrically Administered Seizure Therapy (FEAST) SO BRAIN STIMULATION LA English DT Article DE ECT; Electroconvulsive therapy; FEAST; Focally electrically administered seizure therapy; SPECT; Depression; Brain stimulation ID ELECTROCONVULSIVE-THERAPY; MAJOR DEPRESSION; ECT; STIMULATION; METABOLISM; RECEPTORS; DISORDER; SPECT; FORM AB Introduction: Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). Methods: A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Results: Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. Conclusion: FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. (C) 2014 Elsevier Inc. All rights reserved. C1 [Chahine, George; Atoui, Mia; Nahas, Ziad] Amer Univ Beirut, Dept Psychiat, Beirut 11072020, Lebanon. [Short, Baron; Schmidt, Matthew; Burns, Carol; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC USA. [Spicer, Ken] Med Univ S Carolina, Dept Radiol, Charleston, SC USA. [Schmidt, Matthew; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Sackeim, Harold A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Sackeim, Harold A.] Columbia Univ, Dept Radiol, New York, NY USA. RP Nahas, Z (reprint author), Amer Univ Beirut, Dept Psychiat, POB 11-0236, Beirut 11072020, Lebanon. EM zn17@aub.edu.lb NR 23 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2014 VL 7 IS 3 BP 483 EP 485 DI 10.1016/j.brs.2014.02.011 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG9KZ UT WOS:000335739400020 PM 24795198 ER PT J AU Gray, ZA Greenberg, SM Press, DZ AF Gray, Zachary A. Greenberg, Steven M. Press, Daniel Z. TI rTMS for Treatment of Depression in a Patient With Cerebral Amyloid Angiopathy: A Case Report on Safety and Efficacy SO BRAIN STIMULATION LA English DT Letter C1 [Gray, Zachary A.; Press, Daniel Z.] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Ctr Stroke Res, Boston, MA 02114 USA. RP Press, DZ (reprint author), Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, 330 Brookline Ave,KS 158, Boston, MA 02215 USA. EM dpress@bidmc.harvard.edu FU NIA NIH HHS [R01 AG26484, R01 AG026484] NR 8 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD MAY-JUN PY 2014 VL 7 IS 3 BP 495 EP 497 DI 10.1016/j.brs.2014.02.013 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG9KZ UT WOS:000335739400028 PM 24674781 ER PT J AU Luo, X Mitra, D Sullivan, RJ Wittner, BS Kimura, AM Pan, SW Hoang, MP Brannigan, BW Lawrence, DP Flaherty, KT Sequist, LV McMahon, M Bosenberg, MW Stott, SL Ting, DT Ramaswamy, S Toner, M Fisher, DE Maheswaran, S Haber, DA AF Luo, Xi Mitra, Devarati Sullivan, Ryan J. Wittner, Ben S. Kimura, Anya M. Pan, Shiwei Hoang, Mai P. Brannigan, Brian W. Lawrence, Donald P. Flaherty, Keith T. Sequist, Lecia V. McMahon, Martin Bosenberg, Marcus W. Stott, Shannon L. Ting, David T. Ramaswamy, Sridhar Toner, Mehmet Fisher, David E. Maheswaran, Shyamala Haber, Daniel A. TI Isolation and Molecular Characterization of Circulating Melanoma Cells SO CELL REPORTS LA English DT Article ID GENE-EXPRESSION ANALYSIS; TUMOR-CELLS; CUTANEOUS MELANOMA; SINGLE-CELL; IN-SITU; METASTASIS; CARCINOMAS; STAGE; RNA AB Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma. C1 [Luo, Xi; Sullivan, Ryan J.; Wittner, Ben S.; Kimura, Anya M.; Pan, Shiwei; Brannigan, Brian W.; Lawrence, Donald P.; Flaherty, Keith T.; Sequist, Lecia V.; Stott, Shannon L.; Ting, David T.; Ramaswamy, Sridhar; Fisher, David E.; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Mitra, Devarati; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Sullivan, Ryan J.; Lawrence, Donald P.; Flaherty, Keith T.; Sequist, Lecia V.; Stott, Shannon L.; Ting, David T.; Ramaswamy, Sridhar; Haber, Daniel A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sullivan, Ryan J.; Hoang, Mai P.; Lawrence, Donald P.; Flaherty, Keith T.; Sequist, Lecia V.; Stott, Shannon L.; Ting, David T.; Ramaswamy, Sridhar; Toner, Mehmet; Fisher, David E.; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Bosenberg, Marcus W.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA. [Stott, Shannon L.; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA 02129 USA. [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Toner, Mehmet; Maheswaran, Shyamala] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Luo, Xi; Haber, Daniel A.] Howard Hughes Med Inst, Bethesda, MD 20815 USA. RP Maheswaran, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM maheswaran@helix.mgh.harvard.edu; haber@helix.mgh.harvard.edu OI Ting, David/0000-0002-3261-2322 FU Stand Up To Cancer; Howard Hughes Medical Institute; Melanoma Research Foundation; National Foundation for Cancer Research; NIH [NIH CA129933, NIBIB EB008047] FX The authors thank C. Hart, A. McGovern, C. Koris, and the Massachusetts General Hospital clinical research coordinators for help with clinical studies; L. Libby for mouse studies; F. Ozsolak and P. Milos (Helicos) for RNA-seq; and J. Walsh, J. Lennerz, and M. Ulman for microscopy expertise. This work was supported by grants from Stand Up To Cancer (D.A.H., M.T., and S.M.), the Howard Hughes Medical Institute (D.A.H.), the Melanoma Research Foundation (X.L.), the National Foundation for Cancer Research (D.A.H.), and the NIH (NIH CA129933 to D.A.H. and NIBIB EB008047 to D.A.H. and M.T.). Massachusetts General Hospital has filed for patent protection for CTC technology. NR 32 TC 23 Z9 23 U1 1 U2 25 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 MAY PY 2014 VL 7 IS 3 BP 645 EP 653 DI 10.1016/j.celrep.2014.03.039 PG 9 WC Cell Biology SC Cell Biology GA AG6WZ UT WOS:000335560900006 PM 24746818 ER PT J AU Wolf, AR Mootha, VK AF Wolf, Ashley R. Mootha, Vamsi K. TI Functional Genomic Analysis of Human Mitochondrial RNA Processing SO CELL REPORTS LA English DT Article ID RICH PENTATRICOPEPTIDE-REPEAT; MESSENGER-RNA; GENE-EXPRESSION; RESPIRATORY COMPLEXES; BINDING DOMAIN; HELA-CELLS; PROTEIN; MUTATION; IMPORT; LRPPRC AB Both strands of human mtDNA are transcribed in continuous, multigenic units that are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory chain biogenesis. We sought to systematically identify nuclear-encoded proteins that contribute to processing of mtRNAs within the organelle. First, we devised and validated a multiplex MitoString assay that quantitates 27 mature and precursor mtDNA transcripts. Second, we applied MitoString profiling to evaluate the impact of silencing each of 107 mitochondrial-localized, predicted RNA-binding proteins. With the resulting data set, we rediscovered the roles of recently identified RNA-processing enzymes, detected unanticipated roles of known disease genes in RNA processing, and identified new regulatory factors. We demonstrate that one such factor, FASTKD4, modulates the half-lives of a subset of mt-mRNAs and associates with mtRNAs in vivo. MitoString profiling may be useful for diagnosing and deciphering the pathogenesis of mtDNA disorders. C1 [Wolf, Ashley R.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Wolf, Ashley R.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wolf, Ashley R.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Wolf, Ashley R.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02141 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu OI Wolf, Ashley R./0000-0001-8631-9837 FU NSF graduate research fellowship; NIH [GM077465] FX We thank J. Baughman, X.R. Bao, S. Calvo, Y. Sancak, L. Strittmatter, I. Jain, N. Delaney, E. Kovacs-Bogdan, A. Li, S. Vafai, M. Staller, and N.M. Cabili for comments and helpful discussions. We thank the Broad Institute RNAi Platform for shRNA reagents, S. Silver and S. Gopal for advice, R. Boykin and G. Geiss of NanoString Technologies for technical assistance, and the Regev and Shamji groups for access to the nCounter analysis system. We thank M. Guttman, D. Shechner, J. Rinn, D. Scott, and F. Zhang for guidance on experimental protocols. This work was supported by an NSF graduate research fellowship to A.R.W. and an NIH grant (GM077465) to V.K.M. NR 53 TC 23 Z9 23 U1 1 U2 7 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 MAY PY 2014 VL 7 IS 3 BP 918 EP 931 DI 10.1016/j.celrep.2014.03.035 PG 14 WC Cell Biology SC Cell Biology GA AG6WZ UT WOS:000335560900031 PM 24746820 ER PT J AU Binney, ZO Quest, TE Feingold, PL Buchman, T Majesko, AA AF Binney, Zachary O. Quest, Tammie E. Feingold, Paul L. Buchman, Timothy Majesko, Alyssa A. TI Feasibility and Economic Impact of Dedicated Hospice Inpatient Units for Terminally Ill ICU Patients* SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; hospice care; terminal care; healthcare costs; palliative care ID INTENSIVE-CARE-UNIT; OF-LIFE CARE; PALLIATIVE CARE; CONTROLLED-TRIAL; FAMILY-MEMBERS; CRITICALLY-ILL; SUSTAINING TREATMENT; MEDICAL EXPENDITURE; CANCER-PATIENTS; END AB Objectives: End-of-life care is frequently provided in the ICU because patients receiving life-sustaining treatments are often unsuitable for transfer to home or community hospices. In-hospital dedicated hospice inpatient units are a novel option. This study was designed to 1) demonstrate the feasibility of ICU to dedicated hospice inpatient unit transfer in critically ill terminal patients; 2) describe the clinical characteristics of those transferred and compare them to similar patients who were not transferred; and 3) assess the operational and economic impact of dedicated hospice inpatient units. Design: Retrospective chart review. Setting: ICUs and dedicated hospice inpatient units at two southeast urban university hospitals. Interventions: Charts of ICU and dedicated hospice inpatient unit deaths over a 6-month period were reviewed. Patients: Dedicated hospice inpatient unit transfers were identified from hospice administrator records. Missed opportunities were patients admitted to the hospital for more than 48 hours who either adopted a comfort care course or had a planned termination of life-sustaining therapy. Patients were excluded if they were declared brain dead, were organ donors, required high-frequency ventilation, or if there was insufficient information in the medical record to make a determination. Measurements and Main Results: We identified 167 transfers and 99 missed opportunities; 37% of appropriate patients were not transferred. Transfers were older (66.9 vs 60.4 yr; p < 0.05), less likely to use mechanical ventilation (71.9% vs 90.9%) and vasopressors (70.9% vs 95.0%; p < 0.05), and less likely to receive a palliative care consult (70.4% vs 43.4%; p < 0.05) than missed opportunities. Transfers saved 585 ICU bed days. Conclusions: Dedicated hospice inpatient units are a feasible way to provide care for terminal ICU patients, but barriers including lack of knowledge of the units and provider or family comfort with leaving the ICU remain. Dedicated hospice inpatient units are potentially significant sources of bed days and cost savings for hospitals and the healthcare system overall. C1 [Binney, Zachary O.; Majesko, Alyssa A.] Emory Univ, Emory Palliat Care Ctr, Atlanta, GA 30322 USA. [Quest, Tammie E.] Emory Univ, Sch Med, US Dept Vet Affairs, Med Ctr, Atlanta, GA USA. [Quest, Tammie E.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. [Feingold, Paul L.; Buchman, Timothy] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Buchman, Timothy; Majesko, Alyssa A.] Emory Univ, Emory Ctr Crit Care Med, Atlanta, GA 30322 USA. RP Binney, ZO (reprint author), Emory Univ, Emory Palliat Care Ctr, Atlanta, GA 30322 USA. EM zbinney@emory.edu OI Buchman, Timothy/0000-0001-7350-5921; Feingold, Paul/0000-0002-3194-4309 FU James S. McDonnell Foundation FX Dr. Quest is employed by Gentiva Hospice. Dr. Buchman's institution received grant support from the James S. McDonnell Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 41 TC 3 Z9 3 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2014 VL 42 IS 5 BP 1074 EP 1080 DI 10.1097/CCM.0000000000000120 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA AG4IU UT WOS:000335383900022 PM 24351372 ER PT J AU Stahl, D Bittner, EA AF Stahl, David Bittner, Edward A. TI Glucose Control in Pediatric Burn Patients: Refining the Search for the "Sweet Spot"* SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE blood glucose; insulin; burns ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; HYPERGLYCEMIA; MORTALITY; CHILDREN; TRIAL C1 [Stahl, David; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Stahl, D (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2014 VL 42 IS 5 BP 1315 EP 1317 DI 10.1097/CCM.0000000000000200 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA AG4IU UT WOS:000335383900066 PM 24736355 ER PT J AU Pati, S Cole, AJ AF Pati, Sandipan Cole, Andrew J. TI How focal is generalized epilepsy: A distinction with a difference? SO EPILEPSY & BEHAVIOR LA English DT Editorial Material ID ABSENCE SEIZURES; PATHOPHYSIOLOGY C1 [Pati, Sandipan; Cole, Andrew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Epilepsy Serv, WACC 739-L,Fruit St, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.edu OI Cole, Andrew/0000-0002-0828-826X NR 9 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2014 VL 34 BP 127 EP 128 DI 10.1016/j.yebeh.2014.03.007 PG 2 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AG5GN UT WOS:000335447600026 PM 24713435 ER PT J AU Das, S Sarkar, A Ryan, KA Fox, S Berger, AH Juncadella, IJ Bimczok, D Smythies, LE Harris, PR Ravichandran, KS Crowe, SE Smith, PD Ernst, PB AF Das, Soumita Sarkar, Arup Ryan, Kieran A. Fox, Sarah Berger, Alice H. Juncadella, Ignacio J. Bimczok, Diane Smythies, Lesley E. Harris, Paul R. Ravichandran, Kodi S. Crowe, Sheila E. Smith, Phillip D. Ernst, Peter B. TI Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells SO FASEB JOURNAL LA English DT Article DE efferocytosis; mucosal immunity; stomach; bacteria; gastritis ID PHOSPHATIDYLSERINE RECEPTOR; CYTOKINE PRODUCTION; CORPSE CLEARANCE; STEM-CELLS; DIFFERENTIATION; MACROPHAGES; DISEASE; SYSTEM; IDENTIFICATION; HOMEOSTASIS AB After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5-fold increase in the binding of apoptotic GECs to THP-1 cells or peripheral blood monocyte-derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP-1 cells to apoptotic cells inhibited IL-6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects.Das, S., Sarkar, A., Ryan, K. A., Fox, S., Berger, A. H., Juncadella, I. J., Bimczok, D., Smythies, L. E., Harris, P. R., Ravichandran, K. S., Crowe, S. E., Smith, P. D., Ernst, P. B. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells. C1 [Das, Soumita; Sarkar, Arup; Fox, Sarah; Ernst, Peter B.] Univ Calif San Diego, Dept Pathol, Div Comparat Pathol & Med, San Diego, CA 92093 USA. [Crowe, Sheila E.] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA. [Ryan, Kieran A.] Natl Univ Ireland Univ Coll Cork, Dept Microbiol, Cork, Ireland. [Ryan, Kieran A.] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland. [Berger, Alice H.] Broad Inst Massachusetts Inst Technol & Harvard U, Canc Program, Cambridge, MA USA. [Berger, Alice H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Juncadella, Ignacio J.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Juncadella, Ignacio J.; Ravichandran, Kodi S.] Univ Virginia, Beirne Carter Ctr Immunol, Charlottesville, VA USA. [Bimczok, Diane; Smythies, Lesley E.; Smith, Phillip D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Bimczok, Diane; Smythies, Lesley E.; Smith, Phillip D.] Univ Alabama Birmingham, Dept Gastroenterol, Birmingham, AL USA. [Harris, Paul R.] Pontificia Univ Catolica Chile, Sch Med, Unit Gastroenterol & Nutr, Div Pediat, Santiago, Chile. RP Ernst, PB (reprint author), Univ Calif San Diego, Dept Pathol, Div Comparat Pathol & Med, MC 0063, San Diego, CA 92093 USA. EM pernst@ucsd.edu FU U.S. National Institutes of Health [AI079145, DK084063, AI070491, DK61769, DK54495, DK84063, AI83539, RR20136]; University of Alabama at Birmingham Mucosal HIV and Immunobiology Center (Center for Clinical and Translational Science and Immunology, Autoimmunity and Transplantation Pilot Program) [DK64400]; Research Service of the Veterans Administration; University of Virginia Digestive Health Research Center Immunology and Cell Isolation Core and Morphology/Imaging Core [DK67629]; UCSD Neuroscience Microscopy Shared Facility [P30 NS047101]; UCSD Moores Cancer Center Biorepository Tissue Technology Shared Resources [2P30 CA023100]; UCSD Digestive Diseases Research Development Center [DK80506] FX The authors thank Amber Ablack for technical assistance in the maintenance of AGS cells and H. pylori strains; Drs. Scott Vandenberg and Donald Pizzo [University of California, San Diego (UCSD) histology core facility] for the immunohistochemical analysis; Joanne Lannigan, William Ross, Mike Solga, and Elizabeth Wiznerowicz (University of Virginia) for technical assistance; and the University of Texas Medical Branch Protein Biosynthesis and Biomarker Core Laboratory (Galveston, TX, USA) for protein purification. This work was supported by U.S. National Institutes of Health grants AI079145, DK084063, and AI070491 (to P.B.E.), DK61769 (to S.E.C.), and DK54495, DK84063, AI83539, and RR20136; as well as grants to the University of Alabama at Birmingham Mucosal HIV and Immunobiology Center (Center for Clinical and Translational Science and Immunology, Autoimmunity and Transplantation Pilot Program; DK64400), the Research Service of the Veterans Administration (to P.D.S.), the University of Virginia Digestive Health Research Center Immunology and Cell Isolation Core and Morphology/Imaging Core (DK67629), the UCSD Neuroscience Microscopy Shared Facility (P30 NS047101), the UCSD Moores Cancer Center Biorepository Tissue Technology Shared Resources (2P30 CA023100), and the UCSD Digestive Diseases Research Development Center (DK80506). The authors declare no conflict of interest. NR 53 TC 9 Z9 9 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAY PY 2014 VL 28 IS 5 BP 2214 EP 2224 DI 10.1096/fj.13-243238 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AG3RA UT WOS:000335336000024 PM 24509909 ER PT J AU Ablonczy, Z Dahrouj, M Marneros, AG AF Ablonczy, Zsolt Dahrouj, Mohammad Marneros, Alexander G. TI Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels SO FASEB JOURNAL LA English DT Article DE age-related macular degeneration; visual cycle; retinoids; choroidal neovascularization ID AGE-RELATED MACULOPATHY; SUBRETINAL DRUSENOID DEPOSITS; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; BETA-CAROTENE; RANIBIZUMAB; PREVALENCE; EXPRESSION; VISION; EYES AB Patients with nonexudative (dry) age-related macular degeneration (AMD) frequently also develop neovascular (wet) AMD, suggesting a common pathomechanism. Increased vascular endothelial growth factor A (VEGF-A) has been implicated in the pathogenesis of choroidal neovascularization (CNV) in neovascular AMD, while its role in nonexudative AMD that manifests with progressive retinal pigment epithelium (RPE) and photoreceptor degeneration is not well defined. Mice with overall increased VEGF-A levels develop progressive morphological features of both forms of AMD, suggesting that an increase in VEGF-A has a direct age-dependent adverse effect on RPE and photoreceptor function independently of its CNV-promoting proangiogenic effect. Here we provide evidence for this hypothesis and show that morphological RPE abnormalities and retinal thinning in mice with increased VEGF-A levels correlate with progressive age-dependent attenuation of visual function with abnormal electroretinograms and reduced retinal rhodopsin levels. Retinoid profiling revealed a progressive reduction of 11-cis and all-trans retinal in the retinas of these mice, consistent with an impaired retinoid transport between the RPE and photoreceptors. These findings suggest that increased VEGF-A leads to an age-dependent RPE and retinal dysfunction that occurs also at sites where no CNV lesions form. The data support a central role of increased VEGF-A not only in the pathogenesis of neovascular but also of nonexudative AMD.Ablonczy, Z., Dahrouj, M., Marneros, A. G. Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels. C1 [Ablonczy, Zsolt; Dahrouj, Mohammad] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Marneros, Alexander G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Marneros, Alexander G.] Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA USA. RP Marneros, AG (reprint author), CNY 149,Room 3-216,CBRC,MGH East,13thSt, Charlestown, MA 02129 USA. EM amarneros@mgh.harvard.edu FU U.S. National Institutes of Health (NIH)/National Eye Institute (NEI) [NEI R01-EY019297]; NIH/NEI [NEI R01-EY019065]; Medical Scientist Training Program at the Medical University of South Carolina (MUSC); NIH/National Institute of General Medical Sciences [T32 GM008716]; Research to Prevent Blindness; South Carolina Lions Association FX The authors thank Drs. Andras Nagy, Lucile Miquerol, and Annette Damert (University of Toronto, Toronto, ON, Canada) for providing VEGF-Ahyper mice and VEGF-Ahypo mice, Patrice Goletz for technical help, and Drs. Rosalie Crouch and Jie Fan for helpful discussions. This work was supported by a U.S. National Institutes of Health (NIH)/National Eye Institute (NEI) grant to A.G.M. (NEI R01-EY019297), an NIH/NEI grant to Z.A. (NEI R01-EY019065), funding from the Medical Scientist Training Program at the Medical University of South Carolina (MUSC; NIH/National Institute of General Medical Sciences grant T32 GM008716) to M. D., an unrestricted grant of Research to Prevent Blindness to the Department of Ophthalmology at MUSC, and the South Carolina Lions Association. NR 28 TC 19 Z9 19 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAY PY 2014 VL 28 IS 5 BP 2369 EP 2379 DI 10.1096/fj.13-248021 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AG3RA UT WOS:000335336000037 PM 24558195 ER PT J AU Afeiche, MC Bridges, ND Williams, PL Gaskins, AJ Tanrikut, C Petrozza, JC Hauser, R Chavarro, JE AF Afeiche, Myriam C. Bridges, Naima D. Williams, Paige L. Gaskins, Audrey J. Tanrikut, Cigdem Petrozza, John C. Hauser, Russ Chavarro, Jorge E. TI Dairy intake and semen quality among men attending a fertility clinic SO FERTILITY AND STERILITY LA English DT Article DE Infertility; sperm quality; dairy; diet ID GROWTH-FACTOR-I; FOOD FREQUENCY QUESTIONNAIRE; UNITED-STATES; IGF-I; DIETARY PATTERNS; YOUNG MEN; INSULIN; ESTROGENS; MILK; INFERTILITY AB Objective: To examine the relationship between dairy food intake and semen parameters. Design: Longitudinal study. Setting: Academic medical center fertility clinic. Patient(s): One hundred fifty-five men. Intervention(s): None. Main Outcome Measure(s): Total sperm count, sperm concentration, progressive motility, morphology, and semen volume. Result(s): Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22-3.54 servings/d) had 33% (95% confidence interval [CI] 1, 55) higher sperm concentration and 9.3 percentage units (95% CI 1.4, 17.2) higher sperm motility than men in the lowest quartile of intake (<= 0.28 servings/d). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95% CI 1, 51) higher sperm concentration and 8.7 percentage units (95% CI 3.0, 14.4) higher sperm motility. Cheese intake was associated with lower sperm concentration among ever-smokers. In this group, men in the highest tertile of intake (0.82-2.43 servings/d) had 53.2% (95% CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/d). Conclusion(s): Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, whereas cheese intake is related to lower sperm concentration among past or current smokers. (C) 2014 by American Society for Reproductive Medicine. C1 [Afeiche, Myriam C.; Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Bridges, Naima D.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Global Hlth MPH Program, Boston, MA 02115 USA. [Bridges, Naima D.] Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gaskins, Audrey J.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tanrikut, Cigdem] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Tanrikut, Cigdem; Petrozza, John C.; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Petrozza, John C.; Hauser, Russ] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Afeiche, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM mafeiche@hsph.harvard.edu FU National Institutes of Health from National Institutes of Environmental Health Sciences [R01-ES009718]; National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK046200]; Ruth L. Kirschstein National Research Service from National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK 007703-16] FX Supported by National Institutes of Health grants R01-ES009718 from National Institutes of Environmental Health Sciences, P30 DK046200 from National Institute of Diabetes and Digestive and Kidney Diseases. M. C. A. and A.J.G. were supported by a Ruth L. Kirschstein National Research Service Award T32 DK 007703-16 from National Institute of Diabetes and Digestive and Kidney Diseases. NR 38 TC 14 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2014 VL 101 IS 5 BP 1280 EP U24 DI 10.1016/j.fertnstert.2014.02.003 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AG6BX UT WOS:000335504600025 PM 24636397 ER PT J AU Valente, AJ Irimpen, AM Siebenlist, U Chandrasekar, B AF Valente, Anthony J. Irimpen, Anand M. Siebenlist, Ulrich Chandrasekar, Bysani TI OxLDL induces endothelial dysfunction and death via TRAF3IP2: Inhibition by HDL3 and AMPK activators SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Atherosclerosis; Oxidative stress; NADPH oxidases; Endothelial dysfunction; Free radicals ID LOW-DENSITY-LIPOPROTEIN; PROTEIN-KINASE; AIRWAY INFLAMMATION; CELL APOPTOSIS; UP-REGULATION; OXIDIZED LDL; CIKS ACT1; OX-LDL; OXIDATION; RECEPTOR AB Oxidized low-density lipoprotein (oxLDL) induces endothelial cell death through the activation of NF-kappa B and AP-1 pathways. TRAF3IP2 is a redox-sensitive cytoplasmic adapter protein and an upstream regulator of IKK/NF-kappa B and JNK/AP-1. Here we show that oxLDL-induced death in human primary coronary artery endothelial cells (ECs) was markedly attenuated by the knockdown of TRAF3IP2 or the lectin-like oxLDL receptor I (LOX-1). Further, oxLDL induced Nox2/superoxide-dependent TRAF3IP2 expression, IKK/p65 and JNK/c-Jun activation, and LOX-I upregulation, suggesting a reinforcing mechanism. Similarly, the lysolipids present in oxLDL (16:0-LPC and 18:0-LPC) and minimally modified LDL also upregulated TRAF3IP2 expression. Notably, whereas native HDL3 reversed oxLDL-induced TRAF3IP2 expression and cell death, 15-lipoxygenase-modified HDL3 potentiated its proapoptotic effects. The activators of the AMPK/Akt pathway, adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2 expression, and oxLDL/TRAF3IP2-mediated EC death. Further, both HDL3 and adiponectin reversed oxLDL/TRAF3IP2-dependent monocyte adhesion to endothelial cells in vitro. Importantly, TRAF3IP2 gene deletion and the AMPK activators reversed oxLDL-induced impaired vasorelaxation ex vivo. These results indicate that oxLDL-induced endothelial cell death and dysfunction are mediated via TRAF3IP2 and that native HDL3 and the AMPK activators inhibit this response. Targeting TRAF3IP2 could potentially inhibit progression of atherosclerotic vascular diseases. (c) 2014 Elsevier Inc. All rights reserved. C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Irimpen, Anand M.; Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. [Irimpen, Anand M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Siebenlist, Ulrich] NIAID, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu FU Department of Veterans Affairs Research Career Scientist award; VA Office of Research and Development Biomedical Laboratory Research and Development Service Award [1I01BX000246]; NIH/NHLBI [HL-86787] FX B.C. is the recipient of a 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 1I01BX000246 and NIH/NHLBI Grant HL-86787. U.S. is supported by the Intramural Research Program of the NIH/NIAID. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States government. NR 41 TC 15 Z9 18 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY PY 2014 VL 70 BP 117 EP 128 DI 10.1016/j.freeradbiomed.2014.02.014 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AG5VP UT WOS:000335487100012 PM 24561578 ER PT J AU Vargas, R Rauh-Hain, JA Clemmer, J Clark, RM Goodman, A Growdon, WB Schorge, JO del Carmen, MG Horowitz, NS Boruta, DM AF Vargas, Roberto Rauh-Hain, J. Alejandro Clemmer, Joel Clark, Rachel M. Goodman, Annekathryn Growdon, Whitfield B. Schorge, John O. del Carmen, Marcela G. Horowitz, Neil S. Boruta, David M., II TI Tumor size, depth of invasion, and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial neoplasms; Lymph node excision ID CORPUS CANCER; METASTASIS; RISK; LYMPHADENECTOMY; ADENOCARCINOMA; DISSEMINATION; SURVIVAL; TRIAL AB Objectives. The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis. Materials and methods. Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement. Results. The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p < 0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p < 0.001). Conclusions. In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis. (C) 2014 Elsevier Inc. All rights reserved. C1 [Vargas, Roberto; Rauh-Hain, J. Alejandro; Clemmer, Joel; Clark, Rachel M.; Goodman, Annekathryn; Growdon, Whitfield B.; Schorge, John O.; del Carmen, Marcela G.; Boruta, David M., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. [Vargas, Roberto; Horowitz, Neil S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM dboruta@partners.org OI Vargas, Roberto/0000-0003-4262-7824 FU MGH Deborah Kelly Center FX The authors have no financial disclosures to report at this time. Funding for this study was provided by the MGH Deborah Kelly Center. NR 23 TC 18 Z9 21 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2014 VL 133 IS 2 BP 216 EP 220 DI 10.1016/j.ygyno.2014.02.011 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AG6PK UT WOS:000335540700014 PM 24548726 ER PT J AU Bradford, LS Rauh-Hain, A Clark, RM Groeneweg, JW Zhang, L Borger, D Zukerberg, LR Growdon, WB Foster, R Rueda, BR AF Bradford, Leslie S. Rauh-Hain, Alejandro Clark, Rachel M. Groeneweg, Jolijn W. Zhang, Ling Borger, Darrell Zukerberg, Lawrence R. Growdon, Whitfield B. Foster, Rosemary Rueda, Bo R. TI Assessing the efficacy of targeting the phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway in endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; PI3K inhibitor; PI3K/AKT/mTOR pathway ID CLINICAL-TRIALS; PI3K PATHWAY; PARP INHIBITOR; BREAST-CANCER; PHASE-I; CARCINOMA; PTEN; RECURRENT; MUTATIONS; THERAPY AB Objective. Alterations in the PI3K pathway are prevalent in endometrial cancer due to PIK3CA mutation and loss of PTEN. We investigated the anti-tumor activity of the PI3K inhibitor NVP BKM-120 (BKM) as a single agent and in combination with standard cytotoxic chemotherapy in a human primary endometrial xenograft model. Methods. NOD/SCID mice bearing xenografts of primary human tumors with and without PIK3CA gene mutations were divided into two and four arm cohorts with equivalent tumor volumes. BKM was administered alone and in combination with paclitaxel and carboplatin (P/C) and endometrial xenograft tumor volumes were assessed. Tumors from the BKM, P/C, P/C + BKM and vehicle treated mice were processed for determination of PI3K/AKT/mTOR pathway activation. Results. In both single agent experiments, BKM resulted in significant tumor growth suppression starting at days 5-10 compared to the linear growth observed in vehicle treated tumors (p < 0.04 in all experiments). Tumor resurgence manifested between days 14 and 25 (p < 0.03). When BKM was combined with P/C, this resistance pattern failed to develop in three separate xenograft lines (p < 0.05). Synergistic tumor growth suppression (p < 0.05) of only one xenograft tumor with no detected PIK3CA mutation was observed. Acute treatment with BKM led to a decrease in pAKT levels. Conclusion. Independent of PIK3CA gene mutation, BKM mediated inhibition of the PI3K/AKT/mTOR pathway in endometrial tumors precludes tumor growth in a primary xenograft model. While a pattern of resistance emerges, this effect appears to be mitigated by the addition of conventional cytotoxic chemotherapy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bradford, Leslie S.; Rauh-Hain, Alejandro; Clark, Rachel M.; Groeneweg, Jolijn W.; Zhang, Ling; Growdon, Whitfield B.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Bradford, Leslie S.; Rauh-Hain, Alejandro; Clark, Rachel M.; Growdon, Whitfield B.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Borger, Darrell] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Bradford, Leslie S.; Rauh-Hain, Alejandro; Clark, Rachel M.; Groeneweg, Jolijn W.; Borger, Darrell; Zukerberg, Lawrence R.; Growdon, Whitfield B.; Foster, Rosemary; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, THR 901,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU Advanced Medical Research Fund; Vincent Memorial funds; VSB Foundation FX Funding for this project was provided by the Advanced Medical Research Fund (BRR) and Vincent Memorial funds (BRR). We appreciate the efforts of Minji Kim for conducting protein analysis. In addition, we would like to acknowledge the contributions of the clinical research coordinators (Celeste DiGloria and Virginia Byron) who were responsible for educating and consenting our gynecologic patients. Jolijn W. Groeneweg, MD received financial support via a scholarship awarded by the VSB Foundation. Finally, we want to give special thanks to all the patients who have consented to allow their malignant tumors to be part of our research efforts. NR 38 TC 13 Z9 15 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2014 VL 133 IS 2 BP 346 EP 352 DI 10.1016/j.ygyno.2014.02.022 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AG6PK UT WOS:000335540700037 PM 24561032 ER PT J AU Liu, JF Konstantinopoulos, PA Matulonis, UA AF Liu, Joyce F. Konstantinopoulos, Panagiotis A. Matulonis, Ursula A. TI PARP inhibitors in ovarian cancer: Current status and future promise SO GYNECOLOGIC ONCOLOGY LA English DT Review DE PARP inhibitors; BRCA; Ovarian cancer ID RIBOSE POLYMERASE INHIBITOR; NEGATIVE BREAST-CANCER; PEGYLATED LIPOSOMAL DOXORUBICIN; RECURRENT EPITHELIAL OVARIAN; REFRACTORY SOLID TUMORS; BRCA MUTATION CARRIERS; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; PHASE-I; SOMATIC MUTATIONS AB Clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer treatment has rapidly evolved from observations of single-agent in vitro activity of these agents in BRCA-deficient cancer cells in 2005 to the initiation of multiple phase III studies in 2013. With clinical trial design and treatment of ovarian cancer increasingly based on histological and molecular characteristics, PARP inhibitors are on the horizon of becoming the first biologic agents to be used to treat ovarian cancer based upon pre-selection characteristics of the patient's cancer. PARP inhibitors are most active in ovarian cancers that have defects or aberrations in DNA repair; use of these agents has been of particular interest in high grade serous cancers (HGSC), where studies have shown that similar to 50% of HGSC have abnormalities of DNA repair through BRCA germline and somatic mutation, post-translational changes of BRCA, and abnormalities of other DNA repair molecules. In addition, as aberrant DNA pathways in other histological subtypes of ovarian cancer are identified, and through the combination of PARP inhibitors with other biologic agents, the pool of eligible patients who may benefit from PARP inhibitors will likely expand. Pending review by the Food and Drug Administration (FDA) and the outcome of confirmatory phase III studies, PARP inhibitors could become the first FDA-approved biologic agent for ovarian cancer and also the first new FDA-approval in ovarian cancer since carboplatin and gemcitabine were approved for platinum sensitive ovarian cancer in 2006. This review discusses the PARP inhibitors that are currently in testing for ovarian cancer treatment and the future of this class of anti-cancer agents. (C) 2014 Elsevier Inc. All rights reserved. C1 [Liu, Joyce F.; Konstantinopoulos, Panagiotis A.; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Gynecol Oncol Program, Boston, MA 02215 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ursula_matulonis@dfci.harvard.edu FU Stand Up to Cancer [NCT01623349, BKM120]; National Cancer Institute [NCT01116648] FX Joyce Liu and Panagiotis Konstantinopoulos have no financial conflicts. Ursula Matulonis has served on advisory boards for Clovis Pharmaceuticals and Tesaro. Ursula Matulonis is the overall Principal Investigator (PI) of the Stand Up to Cancer-funded study NCT01623349 (Phase I of olaparib and BKM120 for the treatment of recurrent HGSC of the ovary or triple negative breast cancer). Joyce Liu is the PI of the National Cancer Institute-funded study NCT01116648 (Phase land randomized phase II study of olaparib and cediranib for recurrent platinum sensitive ovarian cancer). NR 64 TC 49 Z9 50 U1 3 U2 55 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2014 VL 133 IS 2 BP 362 EP 369 DI 10.1016/j.ygyno.2014.02.039 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AG6PK UT WOS:000335540700039 PM 24607283 ER PT J AU Shapiro, A Chowdary, P Quon, D Lin, J Neelakantan, S Jiang, HY Dodd, N Brennan, A Allen, G Pierce, GF AF Shapiro, Amy Chowdary, Pratima Quon, Doris Lin, Judith Neelakantan, Srividya Jiang, Haiyan Dodd, Nigel Brennan, Aoife Allen, Geoff Pierce, Glenn F. TI Recombinant factor VIII Fc fusion protein as episodic treatment for bleeding: Analysis from the A-LONG Study SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Shapiro, Amy] Univ Clin Bonn, Inst Expt Haematol & Transfus Med, Bonn, Germany. [Chowdary, Pratima] Royal Free Hosp, KD Haemophilia Ctr, London NW3 2QG, England. [Chowdary, Pratima] Royal Free Hosp, Thrombosis Unit, London NW3 2QG, England. [Quon, Doris] Orthoped Hosp, Hemophilia Treatment Ctr, Los Angeles, CA USA. [Lin, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neelakantan, Srividya; Jiang, Haiyan; Dodd, Nigel; Brennan, Aoife; Allen, Geoff; Pierce, Glenn F.] Biogen Idec Hemophilia, Cambridge, MA USA. RI Allen, Geoffrey/S-3535-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 EI 1365-2516 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2014 VL 20 SU 3 SI SI BP 16 EP 16 PG 1 WC Hematology SC Hematology GA AF9BH UT WOS:000335009500063 ER PT J AU Jacobs, RL Harper, N He, WJ Andrews, CP Rather, CG Ramirez, DA Ahuja, SK AF Jacobs, Robert L. Harper, Nathan He, Weijing Andrews, Charles P. Rather, Cynthia G. Ramirez, Daniel A. Ahuja, Sunil K. TI Effect of confounding cofactors on responses to pollens during natural season versus pollen challenge chamber exposure SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergy; pollen; challenge; confounding; season ID ALLERGIC RHINOCONJUNCTIVITIS; VALIDATION; EFFICACY; UNIT AB Background: The severity of allergic rhinoconjunctivitis (AR) symptomatology elicited after exposure to pollen in the absence versus the presence of confounding cofactors, such as in a pollen challenge chamber (PCC) and the natural pollinating season, respectively, might differ. Objective: We sought to determine the correlation of AR severity in the natural season versus out-of-season PCC exposures. Methods: Twenty-four Virginia live oak (VLO)-positive, 14 VLO-negative, 16 mountain cedar (MC) 2 positive, 8 MCnegative, and 26 ragweed-positive participants recorded AR symptoms (total symptom score [TSS]) during the VLO, MC, and ragweed pollinating seasons and during 2 consecutive PCC exposures of 3 hours each to these pollens separately. Results: The TSSs recorded before the natural season were higher than the pre-PCC values. This prepriming was greater among VLO 1 than MC 1 participants, and it blunted further increases in TSSs during the VLO natural season. Nonatopic participants were nonreactive in the PCC. There was wide variation in the level of AR symptomatology after exposure to VLO, MC, or ragweed pollen in the PCC. Prepriming formed the basis for higher AR responses observed in the natural season than in the PCC, resulting in the identification of distinct PCC/natural season endophenotypes and a partial correlation between the TSSs recorded in the natural season versus those recorded in the PCC (r = 5 0.34, 0.54, and 0.65 for VLO+, MC+, and ragweed-positive participants, respectively). Conclusions: Prepriming in the natural pollinating season might obscure the true correlation between AR severity in the natural season versus the PCC. By mitigating confounding cofactors, PCC exposures have utility for evaluation of novel AR therapeutics. C1 [Jacobs, Robert L.; Andrews, Charles P.; Rather, Cynthia G.; Ramirez, Daniel A.] Biogen Res Chamber LLC, San Antonio, TX 78229 USA. [Harper, Nathan; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. [Harper, Nathan; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. RP Jacobs, RL (reprint author), Biogen Res Chamber LLC, 8299 Fredericksburg Rd, San Antonio, TX 78229 USA. EM robert.jacobs7025@sbcglobal.net RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Jacobs, Robert/0000-0002-2831-9086 FU Doris Duke Distinguished Clinical Scientist Award; Burroughs Wellcome Clinical Scientist in Translational Research Award; Max and Minnie Tomerlin Voelcker Scholar Award; Center for Personalized Medicine at the South Texas Veterans Health Care System FX the Doris Duke Distinguished Clinical Scientist Award, the Burroughs Wellcome Clinical Scientist in Translational Research Award, the Max and Minnie Tomerlin Voelcker Scholar Award, and the Center for Personalized Medicine at the South Texas Veterans Health Care System. NR 20 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2014 VL 133 IS 5 BP 1340 EP U558 DI 10.1016/j.jaci.2013.09.051 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA AG5HS UT WOS:000335450700015 PM 24331377 ER PT J AU Bunyavanich, S Rifas-Shiman, SL Platts-Mills, TA Workman, L Sordillo, JE Camargo, CA Gillman, MW Gold, DR Litonjua, AA AF Bunyavanich, Supinda Rifas-Shiman, Sheryl L. Platts-Mills, Thomas A. Workman, Lisa Sordillo, Joanne E. Camargo, Carlos A., Jr. Gillman, Matthew W. Gold, Diane R. Litonjua, Augusto A. TI Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Maternal diet; pregnancy; food allergy; sensitization; asthma; allergic rhinitis; peanut; milk; wheat; childhood ID MATERNAL FOOD-CONSUMPTION; UNITED-STATES; ANTIOXIDANT INTAKE; ATOPIC DISEASE; BIRTH COHORT; RISK-FACTORS; FOLLOW-UP; PREVALENCE; CHILDHOOD; INFANT AB Background: Maternal diet during pregnancy may affect childhood allergy and asthma. Objective: We sought to examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma. Methods: We studied 1277 mother-child pairs from a US prebirth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age, 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum-specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood. Results: Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least 1 food allergen (28.0%). Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs, 3.6 to 8.1). Conclusion: Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma. C1 [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Div Pediat Allergy & Immunol, Dept Pediat, New York, NY 10029 USA. [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Bunyavanich, Supinda] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Rifas-Shiman, Sheryl L.; Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Rifas-Shiman, Sheryl L.; Sordillo, Joanne E.; Camargo, Carlos A., Jr.; Gillman, Matthew W.; Gold, Diane R.; Litonjua, Augusto A.] Harvard Univ, Sch Med, Boston, MA USA. [Platts-Mills, Thomas A.; Workman, Lisa] Univ Virginia Hlth Syst, Asthma & Allerg Dis Ctr, Charlottesville, VA USA. [Sordillo, Joanne E.; Camargo, Carlos A., Jr.; Gold, Diane R.; Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Gold, Diane R.; Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. RP Bunyavanich, S (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl 1198, New York, NY 10029 USA. EM supinda@post.harvard.edu FU National Institutes of Health [AI093538, HL61907, HL64925, HD34568, AI35786, HL68041, AI102960, HL007427] FX This study was supported by the National Institutes of Health (grant nos. AI093538, HL61907, HL64925, HD34568, AI35786, HL68041, AI102960, and HL007427). NR 63 TC 26 Z9 29 U1 7 U2 34 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2014 VL 133 IS 5 BP 1373 EP 1382 DI 10.1016/j.jaci.2013.11.040 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA AG5HS UT WOS:000335450700020 PM 24522094 ER PT J AU Jackevicius, CA Fan, CS Warner, A AF Jackevicius, Cynthia A. Fan, Cindy Shutieng Warner, Alberta TI Clinical Outcomes of Erythropoietin Use in Heart Failure Patients With Anemia of Chronic Kidney Disease SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Cardiac; health policy; outcome research ID PRESERVED EJECTION FRACTION; DARBEPOETIN-ALPHA; EPOETIN-ALPHA; SUBCUTANEOUS ERYTHROPOIETIN; STIMULATING AGENTS; HEMOGLOBIN LEVEL; INTRAVENOUS IRON; MORTALITY; MORBIDITY; TRIAL AB Background: Anemia and chronic kidney disease are common disorders in heart failure (HF) patients and are associated with increased morbidity and mortality. This study assessed clinical outcomes associated with erythropoietin (EPO) treatment in this cardiorenal anemia syndrome (CRAS) population. Methods and Results: This was a retrospective cohort study of Veterans Affairs patients with CRAS from January 2003 to December 2006. The primary outcome was a composite of death, acute coronary syndrome (ACS), HF, and stroke. Multiple Cox regression modeling was used to evaluate the outcome in patients prescribed (n = 213) and not prescribed EPO (n = 1845). Adjusted incidence of mortality was statistically significantly higher in EPO than in non-EPO users (33.8% vs 19.7%; hazard ratio 1.40, 95% confidence interval 1.06-1.85; P = .02). The unadjusted composite of cardiovascular events/death was higher in the EPO group, but not statistically significant when adjusted for confounders (P = .12). Crude ACS events were documented in 18.8% and 10.8% patients (P = .001), and stroke events occurred in 22.5% and 18.3% patients (P = .14) in EPO and non-EPO groups, respectively. Conclusions: We found that in CRAS patients, EPO use was associated with increased risk of mortality and a trend toward increased cardiovascular events. Therefore, clinicians considering EPO use in CRAS patients should assess whether any potential benefits outweigh the risks of use. C1 [Jackevicius, Cynthia A.; Fan, Cindy Shutieng] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. [Jackevicius, Cynthia A.; Fan, Cindy Shutieng; Warner, Alberta] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Warner, Alberta] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E 2nd St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu FU American College of Clinical Pharmacy Watson Anemia Investigator Development Research Award FX American College of Clinical Pharmacy Watson Anemia Investigator Development Research Award. NR 35 TC 4 Z9 5 U1 1 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD MAY PY 2014 VL 20 IS 5 BP 327 EP 333 DI 10.1016/j.cardfai1.2014.02.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG9AI UT WOS:000335710500007 PM 24530942 ER PT J AU Bakker, JP Campana, LM Montesi, SB Balachandran, J DeYoung, PN Smales, E Patel, SR Malhotra, A AF Bakker, Jessie P. Campana, Lisa M. Montesi, Sydney B. Balachandran, Jayshankar DeYoung, Pamela N. Smales, Erik Patel, Sanjay R. Malhotra, Atul TI A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Obstructive sleep apnea; Heart rate variability; Weight-loss surgery; Continuous positive airway pressure ID HEART-RATE-VARIABILITY; REPRODUCIBILITY; ASSOCIATION; IMPACT; BAROREFLEX; STATISTICS; FAILURE; DISEASE; HUMANS; TONE AB Background: We have previously demonstrated that severity of obstructive sleep apnea (OSA) as measured by the apnea-hypopnea index (AHI) is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability (HRV). Methods: We aimed to assess time-domain HRV measured over 5-min while awake in a trial of obese subjects undergoing one of two OSA therapies: weight-loss surgery (n = 12, 2 males, median and interquartile range (IQR) for BMI 43.7 [42.0, 51.4] kg/m(2), and AHI 18.1 [16.3, 67.5] events/h) or continuous positive airway pressure (CPAP) (n = 15, 11 males, median BMI 33.8 [31.3, 37.9] kg/m(2), and AHI 36.5 [24.7, 77.3] events/h). Polysomnography was followed by electrocardiography during wakefulness; measurements were repeated at 6 and 12-18 months post-intervention. Results: Despite similar measurements at baseline, subjects who underwent surgery exhibited greater improvement in short-term HRV than those who underwent CPAP (p = 0.04). Conclusions: Our data suggest a possible divergence in autonomic function between the effects of weight loss resulting from bariatric surgery, and the amelioration of obstructive respiratory events resulting from CPAP treatment. Randomized studies are necessary before clinical recommendations can be made. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bakker, Jessie P.; Campana, Lisa M.; Montesi, Sydney B.; Patel, Sanjay R.; Malhotra, Atul] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Bakker, Jessie P.; Campana, Lisa M.; Montesi, Sydney B.; Patel, Sanjay R.; Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA. [Montesi, Sydney B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Balachandran, Jayshankar] Univ Chicago, Dept Med, Sect Pulm & Crit Care, Sleep Disorders Ctr, Chicago, IL 60637 USA. [DeYoung, Pamela N.; Smales, Erik; Malhotra, Atul] Univ Calif San Diego, Pulm & Crit Care Div, La Jolla, CA 92093 USA. RP Bakker, JP (reprint author), Div Sleep Med, 221 Longwood Ave 036BLI, Boston, MA 02115 USA. EM jpbakker@partners.org OI Balachandran, Jay/0000-0001-5574-4662; Patel, Sanjay/0000-0002-9142-5172 FU USA National Institutes of Health [5R01HL048531-16, R01 B1085188-02, R01 HL090897-01A2, 1R01HL110350-01A1, R01HL110350-01, K24HL093218-01A1, P01 HL 095491]; American Heart Association [0840159 N] FX This work was supported by the USA National Institutes of Health (5R01HL048531-16, R01 B1085188-02, R01 HL090897-01A2, 1R01HL110350-01A1, R01HL110350-01, K24HL093218-01A1, and P01 HL 095491) and the American Heart Association (0840159 N). NR 31 TC 2 Z9 2 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAY-JUN PY 2014 VL 47 IS 3 BP 364 EP 373 DI 10.1016/j.jelectrocard.2014.02.008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG9BD UT WOS:000335712700017 PM 24636793 ER PT J AU Njoku, VC Howard, TJ Shen, C Zyromski, NJ Schmidt, CM Pitt, HA Nakeeb, A Lillemoe, KD AF Njoku, Victor C. Howard, Thomas J. Shen, Changyu Zyromski, Nicholas J. Schmidt, C. Max Pitt, Henry A. Nakeeb, Attila Lillemoe, Keith D. TI Pyogenic Liver Abscess Following Pancreaticoduodenectomy: Risk Factors, Treatment, and Long-Term Outcome SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Pyogenic liver abscess; Complications; Pancreas; Surgery; Pancreaticoduodenectomy ID PREOPERATIVE BILIARY DRAINAGE; INTERNATIONAL STUDY-GROUP; PANCREATIC RESECTION; CONSECUTIVE PATIENTS; BLOOD-TRANSFUSION; HEPATIC-ABSCESS; COMPLICATIONS; SURGERY; DEFINITION; THROMBOSIS AB Pancreaticoduodenectomy (PD) remains a challenging operation with a 40 % postoperative complication rate. Pyogenic liver abscess (PLA) is an uncommon complication following PD with little information on its incidence or treatment. This study was done to examine the incidence, risk factors, treatment, and long-term outcome of PLA after PD. We retrospectively reviewed 1,189 patients undergoing PD (N = 839) or distal pancreatectomy (DP) (N = 350) at a single institution over a 14-year period (January 1, 1994-January 1, 2008). Pancreatic databases (PD and DP) were queried for postoperative complications and cross-checked through a hospital-wide database using ICD-9 codes 572.0 (PLA) and 006.3 (amebic liver abscess) as primary or secondary diagnoses. No PLA occurred following DP. Twenty-two patients (2.6 %) developed PLA following PD. These 22 patients were matched (1:3) for age, gender, year of operation, and indication for surgery with 66 patients without PLA following PD. PLA occurred in 2.6 % (22/839) of patients following PD, with 13 patients (59.1 %) having a solitary abscess and 9 (40.9 %) multiple abscesses. Treatment involved antibiotics and percutaneous drainage (N = 15, 68.2 %) or antibiotics alone (N = 7, 31.8 %) with a mean hospital stay of 12 days. No patient required surgical drainage, two abscesses recurred, and all subsequently resolved. Three patients (14 %) died related to PLA. Postoperatively, patients with biliary fistula (13.6 vs. 0 %, p = 0.014) or who required reoperation (18.2 vs. 1.5 %, p = 0.013) had a significantly higher rate of PLA than matched controls. Long-term follow-up showed equivalent 1-year (79 vs.74 %), 2-year (50 vs. 57 %), and 3-year (38 vs. 33 %) survival rates and hepatic function between patients with PLA and matched controls. Postoperative biliary fistula and need for reoperation are risk factors for PLA following PD. Antibiotics and selective percutaneous drainage was effective in 86 % of patients with no adverse effects on long-term hepatic function or survival. C1 [Njoku, Victor C.; Howard, Thomas J.; Shen, Changyu] Indiana Univ Sch Med, Dept Surg & Biostat, Indianapolis, IN 46202 USA. [Zyromski, Nicholas J.; Schmidt, C. Max] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Pitt, Henry A.] Temple Univ, Dept Surg, Philadelphia, PA 19122 USA. [Nakeeb, Attila; Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Zyromski, NJ (reprint author), Indiana Univ Sch Med, Dept Surg, Emerson Hall 519,545 Barnhill Dr, Indianapolis, IN 46202 USA. EM nzyromsk@iupui.edu NR 32 TC 4 Z9 5 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2014 VL 18 IS 5 BP 922 EP 928 DI 10.1007/s11605-014-2466-8 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AG9NE UT WOS:000335745300006 PM 24510300 ER PT J AU Goldberg, RF Reid-Lombardo, KM Hoyt, D Pellegrini, C Rattner, DW Kent, T Jones, D AF Goldberg, Ross F. Reid-Lombardo, Kaye M. Hoyt, David Pellegrini, Carlos Rattner, David W. Kent, Tara Jones, Daniel TI Will There Be A Good General Surgeon When You Need One? SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Surgeon shortage; Health care policy; Affordable health care act; Advocacy ID SURGICAL CARE; SHORTAGE; ACCESS; HEALTH; STATES AB The Public Policy & Advocacy Committee sponsored the panel on the topic of "Will There Be a General Surgeon When You Need One?" at the 2012 Annual Meeting of the SSAT. The panel of experts was convened to formulate recommendations to help general surgeons adapt to the changing landscape which will undoubtedly affect the practice of surgery in the future. The invited speakers were Drs. David Hoyt, Carlos Pellegrini, Kaye M. Reid-Lombardo, and David Rattner. The session was moderated by Drs. Ross Goldberg and Tara Kent. The invited presentations and audience commentary are the basis of this manuscript. C1 [Goldberg, Ross F.] Maricopa Cty Gen Hosp, Dept Surg, Phoenix, AZ USA. [Reid-Lombardo, Kaye M.] Mayo Clin, Dept Surg, Rochester, MN 55905 USA. [Hoyt, David] Amer Coll Surg, Chicago, IL USA. [Pellegrini, Carlos] Univ Washington, Dept Surg, Med Ctr, Seattle, WA 98195 USA. [Rattner, David W.] Massachusetts Gen Hosp, Div Gastrointestinal & Gen Surg, Boston, MA 02114 USA. [Kent, Tara; Jones, Daniel] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Kent, Tara; Jones, Daniel] SSAT Soc Surg Alimentary Tract, Publ Policy & Advocacy Comm, Beverly, MA USA. RP Reid-Lombardo, KM (reprint author), Mayo Clin, Dept Surg, 200 First St SW, Rochester, MN 55905 USA. EM Reidlombardo.kaye@mayo.edu FU NHLBI NIH HHS [R01 HL119248]; NIBIB NIH HHS [R01 EB009362, R01 EB014305, R01 EB010037, R01 EB005807] NR 25 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2014 VL 18 IS 5 BP 1032 EP 1039 DI 10.1007/s11605-013-2416-x PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AG9NE UT WOS:000335745300021 PM 24352612 ER PT J AU Bordeianou, L Hicks, CW Kaiser, AM Alavi, K Sudan, R Wise, PE AF Bordeianou, Liliana Hicks, Caitlin W. Kaiser, Andreas M. Alavi, Karim Sudan, Ranjan Wise, Paul E. TI Rectal Prolapse: An Overview of Clinical Features, Diagnosis, and Patient-Specific Management Strategies SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Rectal prolapse; Management; Surgery; Rectopexy; D'Hoore Procedure; Altemeier Procedure; Delorme Procedure ID PELVIC FLOOR DISORDERS; QUALITY-OF-LIFE; ABDOMINAL RECTOPEXY; PERINEAL PROCTECTOMY; SURGICAL-MANAGEMENT; PRACTICE PARAMETERS; FECAL INCONTINENCE; RANDOMIZED-TRIAL; RECURRENCE; INTUSSUSCEPTION AB Rectal prolapse can present in a variety of forms and is associated with a range of symptoms including pain, incomplete evacuation, bloody and/or mucous rectal discharge, and fecal incontinence or constipation. Complete external rectal prolapse is characterized by a circumferential, full-thickness protrusion of the rectum through the anus, which may be intermittent or may be incarcerated and poses a risk of strangulation. There are multiple surgical options to treat rectal prolapse, and thus care should be taken to understand each patient's symptoms, bowel habits, anatomy, and pre-operative expectations. Preoperative workup includes physical exam, colonoscopy, anoscopy, and, in some patients, anal manometry and defecography. With this information, a tailored surgical approach (abdominal versus perineal, minimally invasive versus open) and technique (posterior versus ventral rectopexy +/- sigmoidectomy, for example) can then be chosen. We propose an algorithm based on available outcomes data in the literature, an understanding of anorectal physiology, and expert opinion that can serve as a guide to determining the rectal prolapse operation that will achieve the best possible postoperative outcomes for individual patients. C1 [Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hicks, Caitlin W.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. [Kaiser, Andreas M.] Univ So Calif, Dept Colorectal Surg, Los Angeles, CA 90033 USA. [Alavi, Karim] UMass Mem Med Ctr, Dept Surg, Worcester, MA 01605 USA. [Sudan, Ranjan] Duke Univ, Dept Surg, Med Ctr, Durham, NC 27710 USA. [Wise, Paul E.] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org OI Wise, Paul/0000-0003-3798-7913 FU Cancer Prevention Pharmaceuticals FX L.B., C. W. H., A. M. K., K. A., and R. S. have no disclosures. P. E. W. has no disclosures related to this work but does have a research grant from Cancer Prevention Pharmaceuticals and has served on an advisory board for Myriad Genetics. NR 47 TC 14 Z9 14 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2014 VL 18 IS 5 BP 1059 EP 1069 DI 10.1007/s11605-013-2427-7 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AG9NE UT WOS:000335745300025 PM 24352613 ER PT J AU Goldsmith, EC Bradshaw, AD Zile, MR Spinale, FG AF Goldsmith, Edie C. Bradshaw, Amy D. Zile, Michael R. Spinale, Francis G. TI Myocardial fibroblast-matrix interactions and potential therapeutic targets SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Review DE Extracellular matrix; Fibroblast; Myofibroblast; Integrin; Discoidin Domain Receptor; Transformation ID RECEPTOR TYROSINE KINASE; DISCOIDIN DOMAIN RECEPTOR-1; PROCOLLAGEN C-PROTEINASE; VASCULAR SMOOTH-MUSCLE; MESENCHYMAL STEM-CELLS; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; CARDIAC FIBROBLASTS; PRESSURE-OVERLOAD; ACTIVATION PROTEIN AB The cardiac extracellular matrix (ECM) is a dynamic structure, adapting to physiological and pathological stresses placed on the myocardium. Deposition and organization of the matrix fall under the purview of cardiac fibroblasts. While often overlooked compared to myocytes, fibroblasts play a critical role in maintaining ECM homeostasis under normal conditions and in response to pathological stimuli assume an activated, myofibroblast phenotype associated with excessive collagen accumulation contributing to impaired cardiac function. Complete appreciation of fibroblast function is hampered by the lack of fibroblast-specific reagents and the heterogeneity of fibroblast precursors. This is further complicated by our ability to dissect-the role of myofibroblasts versus fibroblasts in myocardial in remodeling. This review highlights critical points in the regulation of collagen deposition by fibroblasts, the current panel of molecular tools used to identify fibroblasts and the role of fibroblast-matrix interactions in fibroblast function and differentiation into the myofibroblast phenotype. The clinical potential of exploiting differences between fibroblasts and myofibroblasts and using them to target specific fibroblast populations is also discussed. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium." (C) 2014 Elsevier Ltd. All rights reserved. C1 [Goldsmith, Edie C.; Spinale, Francis G.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA. [Bradshaw, Amy D.; Zile, Michael R.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Bradshaw, Amy D.; Zile, Michael R.] Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. [Spinale, Francis G.] Univ S Carolina, Sch Med, Cardiovasc Translat Res Ctr, Columbia, SC USA. [Spinale, Francis G.] WJB Dorn Vet Affairs Med Ctr, Columbia, SC USA. RP Goldsmith, EC (reprint author), Univ S Carolina, Sch Med, Dept Cell Biol & Anat, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM edie.goldsmith@uscmed.sc.edu FU American Heart Association; National Institutes of Health grant [HL095608]; Veterans' Affairs Health Administration [1101BX001385-01A1]; Research Service of the Department of Veterans Affairs FX This work was supported by an American Heart Association Grant-In-Aid (ECG), by the National Institutes of Health grant HL095608 (FGS), and Merit Award 1101BX001385-01A1 to ADB from the Veterans' Affairs Health Administration. Drs. Francis Spinale and Michael Zile are supported by the Research Service of the Department of Veterans Affairs. The authors would like to thank Shaun Riffle for graphics assistance and Charity Fix and Lorain Junor for staining and microscopy. NR 99 TC 21 Z9 21 U1 1 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2014 VL 70 BP 92 EP 99 DI 10.1016/j.yjmcc2014.01.008 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA AG9BY UT WOS:000335714900012 PM 24472826 ER PT J AU Hausmann, LRM Parks, A Youk, AO Kwoh, CK AF Hausmann, Leslie R. M. Parks, Acacia Youk, Ada O. Kwoh, C. Kent TI Reduction of Bodily Pain in Response to an Online Positive Activities Intervention SO JOURNAL OF PAIN LA English DT Article DE Pain management; internet; intervention studies; mind-body therapies; happiness ID HEALTH SURVEY QUESTIONNAIRE; OUTCOME MEASURE; SOCIAL SUPPORT; PSYCHOLOGY; DIRECTIONS; SF-36; CARE; PSYCHOTHERAPY; METAANALYSIS; PEOPLE AB Inducing temporary positive states reduces pain and increases pain tolerance in laboratory studies. We tested whether completing positive activities in one's daily life produces long-term reductions in self-reported bodily pain in a randomized controlled trial of an online positive activities intervention. Participants recruited via the Web were randomly assigned to complete 0, 2, 4, or 6 positive activities administered online over a 6-week period. Follow-up assessments were collected at the end of 6 weeks and at 1, 3, and 6 months postintervention. We used linear mixed effects models to examine whether the intervention reduced pain over time among those who had a score <67 on the bodily pain subscale of the Short Form-36 at baseline (N = 417; pain scores range from 0 to 100; higher scores indicate less pain). Mean pain scores improved from baseline to 6 months in the 2-activity (55.7 to 67.4), 4-activity (54.2 to 71.0), and 6-activity (50.9 to 67.9) groups. Improvements were significantly greater (P < .05) in the 4-activity and 6-activity groups than in the 0-activity control group (54.1 to 62.2) in unadjusted and adjusted models. This study suggests that positive activities administered online can reduce bodily pain in adults with at least mild to moderate baseline pain. Perspective: This study demonstrates that teaching people simple positive activities can decrease reported levels of bodily pain; moreover, these activities can be administered over the internet, a potential avenue for broadly disseminating health interventions at relatively low costs and with high sustainability. Published by Elsevier Inc. on behalf of the American Pain Society C1 [Hausmann, Leslie R. M.; Youk, Ada O.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Hausmann, Leslie R. M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Youk, Ada O.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Parks, Acacia] Hiram Coll, Dept Psychol, Hiram, OH USA. [Kwoh, C. Kent] Univ Arizona, Div Rheumatol, Tucson, AZ USA. [Kwoh, C. Kent] Univ Arizona, Arthrit Ctr, Tucson, AZ USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot CHERP, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM leslie.hausmann@gmail.com OI Youk, Ada/0000-0001-6912-9759 NR 35 TC 6 Z9 6 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAY PY 2014 VL 15 IS 5 BP 560 EP 567 DI 10.1016/j.jpain.2014.02.004 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG9AU UT WOS:000335711700011 PM 24568751 ER PT J AU O'Donovan, A AF O'Donovan, Aoife TI Inflammation and Depression: Unraveling the Complex Interplay in Inflammatory Bowel Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material C1 [O'Donovan, Aoife] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP O'Donovan, A (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, 4150 Clement St,Bldg 16, San Francisco, CA 94121 USA. EM aoife.odonovan@ucsf.edu NR 12 TC 5 Z9 5 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2014 VL 58 IS 5 BP 541 EP 542 DI 10.1097/MPG.0000000000000292 PG 2 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AG8FG UT WOS:000335653600007 PM 24385077 ER PT J AU Modarressi, T AF Modarressi, Taher TI Question of an Infectious Etiology or Contribution to the Pathogenesis of Infantile Hypertrophic Pyloric Stenosis SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE pyloric stenosis; NOS1; nitric oxide; neuronal nitric oxide synthase; Heliobacter pylori; infantile hypertrophic pyloric stenosis; infectious etiology ID NITRIC-OXIDE SYNTHASE; EPSTEIN-BARR-VIRUS; HELICOBACTER-PYLORI; SEX-DIFFERENCES; CELLS; EXPRESSION; ULCER; SUSCEPTIBILITY; ERADICATION; PERFORATION AB Infantile hypertrophic pyloric stenosis is a concerning cause of nonbilious vomiting in the neonatal population. Although a number of etiological theories exist, its exact cause remains nebulous. The question of an infectious etiology (or contribution) has been previously examined in case reports and case series, with recent support through suggestions of seasonality and familial aggregation with unclear inheritance patterns. The present review discusses the published literature regarding infectious etiologies of infantile hypertrophic pyloric stenosis. Furthermore, it attempts to demonstrate that newer research regarding an NOS1 genetic etiology does not exclude, but rather can be consistent with, an infectious etiology. C1 [Modarressi, Taher] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Modarressi, T (reprint author), Dept Internal Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM tmodarressi@partners.org NR 60 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2014 VL 58 IS 5 BP 546 EP 548 DI 10.1097/MPG.0000000000000261 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AG8FG UT WOS:000335653600011 PM 24345839 ER PT J AU Russell, GH Kaplan, JL Youngster, I Baril-Dore, M Schindelar, L Hohmann, E Winter, HS AF Russell, George H. Kaplan, Jess L. Youngster, Ilan Baril-Dore, Mariah Schindelar, Lili Hohmann, Elizabeth Winter, Harland S. TI Fecal Transplant for Recurrent Clostridium difficile Infection in Children With and Without Inflammatory Bowel Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE recurrent Clostridium difficile infection; fecal microbiome transplant; ulcerative colitis; inflammatory bowel disease; Crohn disease ID ANTIBIOTIC-ASSOCIATED DIARRHEA; MICROBIOTA TRANSPLANTATION; ULCERATIVE-COLITIS; GUT MICROBIOTA; DONOR FECES; BACTERIOTHERAPY; ENEMA; FLORA; EPIDEMIOLOGY AB Ten children at our institution received single-infusion fecal microbiome transplant (FMT) using healthy, related screened donor stool to treat recurrent Clostridium difficile infection (RCDI) via nasogastric tube (2 patients) or colonoscopic delivery. Nine of the 10 (90%) children had resolution of their symptoms after a single-infusion FMT with follow-up of 1 month to 4 years. No concerning related adverse events were recognized during short- or long-term follow-up. Three of these children had concomitant inflammatory bowel disease and 2 of these 3 (66%) patients cleared RCDI with no clinical change in their underlying inflammatory bowel disease clinical activity as assessed by Physician's Global Assessment. All of the patients who had clinical improvement of gastrointestinal symptoms of RCDI while treated with antibiotics had lasting return of baseline health after FMT. C1 [Russell, George H.; Kaplan, Jess L.; Baril-Dore, Mariah; Schindelar, Lili; Winter, Harland S.] MassGen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. [Youngster, Ilan] Childrens Hosp Boston, Div Pediat Infect Dis, Boston, MA USA. [Hohmann, Elizabeth] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Russell, GH (reprint author), MassGen Hosp Children, 175 Cambridge St,CPZ S5, Boston, MA 02114 USA. EM ghrussell@partners.org RI Youngster, Ilan/J-5047-2014 OI Youngster, Ilan/0000-0001-5233-1213 NR 35 TC 21 Z9 23 U1 1 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2014 VL 58 IS 5 BP 588 EP 592 DI 10.1097/MPG.0000000000000283 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AG8FG UT WOS:000335653600018 PM 24792627 ER PT J AU Duro, D Mitchell, PD Mehta, NM Bechard, LJ Yu, YM Jaksic, T Duggan, C AF Duro, Debora Mitchell, Paul D. Mehta, Nilesh M. Bechard, Lori J. Yu, Yong-Ming Jaksic, Tom Duggan, Christopher TI Variability of Resting Energy Expenditure in Infants and Young Children With Intestinal Failure-Associated Liver Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE intestinal failure-associated liver disease; intestinal failure; resting energy expenditure; short bowel syndrome ID SHORT-BOWEL SYNDROME; CRITICALLY-ILL CHILDREN; TERM PARENTERAL-NUTRITION; BODY-COMPOSITION; UNITED-STATES; FAT; CHOLESTASIS; EXPERIENCE; MANAGEMENT; SURVIVAL AB Objective: The aim of the study was to determine, in a cohort of young children with intestinal failure (IF), whether the estimates of basal metabolic rate (BMR) by standard equations can approximate measured resting energy expenditure (REE) by indirect calorimetry (IC). Methods: IC was performed using the dilutional canopy technique. REE measurements were compared with standard, age-based estimation equations (World Health Organization) for BMR. Subjects were classified as hypermetabolic (REE > 110% BMR), hypometabolic (REE < 90% BMR), or normal (REE = 90%-110% BMR). Results: Twenty-eight IF patients (11 girls, 17 boys) had an underlying diagnosis of necrotizing enterocolitis (n = 10) or a congenital gastrointestinal defect (n = 18). Median age was 5.3 months. Median interquartile range (IQR) REE was 46 (42-58) kcal center dot kg(-1) center dot day(-1). Median (IQR) total energy intake provided 209% (172%-257%) of REE, with parenteral nutrition providing 76% (23%) of total energy intake. REE was variable, with 39% (n = 11) of measurements hypermetabolic, 39% (n = 11) hypometabolic, and the remaining 21% (n = 6) normal. Although REE was well correlated with estimated BMR (r = 0.82, P < 0.0001), estimated BMR was not consistently an adequate predictor of REE. BMR over- or underestimated REE by >10 kcal center dot kg(-1) center dot day(-1) in 15 of 28 (54%) patients. REE was not significantly correlated with severity of liver disease, nutritional status, total energy intake, or gestational age. Conclusions: Energy expenditure is variable among children with IF and IF-associated liver disease, with approximately 80% of our cohort exhibiting either hypo- or hypermetabolism. Standard estimation equations frequently do not correctly predict individual REE. Longitudinal studies of energy expenditure and body composition may be needed to guide provision of nutrition regimens. C1 [Duro, Debora; Bechard, Lori J.; Duggan, Christopher] Boston Childrens Hosp, Div GI Nutr, Boston, MA 02115 USA. [Mitchell, Paul D.] Boston Childrens Hosp, Ctr Clin Res, Boston, MA 02115 USA. [Jaksic, Tom] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Mehta, Nilesh M.] Boston Childrens Hosp, Dept Crit Care, Boston, MA 02115 USA. [Yu, Yong-Ming] Massachusetts Gen Hosp, Burn Unit, Boston, MA 02114 USA. [Yu, Yong-Ming] Shriners Hosp Children, Boston, MA USA. RP Duggan, C (reprint author), Boston Childrens Hosp, Div GI Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.duggan@childrens.harvard.edu RI Mehta, Nilesh/G-7073-2016 FU NIH [T32-HD43034-05A1]; Clinical Nutrition Research Center (NIH) [P30 DK40561-13]; Children's Hospital, Boston; NICHD [K24HD058795] FX D.D. was supported by the following grants: Institutional Grant (NIH T32-HD43034-05A1), Pilot Feasibility from the Clinical Nutrition Research Center (NIH #P30 DK40561-13), and the Junior Faculty Career Development Award from Children's Hospital, Boston. C. D. was supported in part by NICHD K24HD058795. The other authors report no conflicts of interest. NR 34 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2014 VL 58 IS 5 BP 637 EP 641 DI 10.1097/MPG.0000000000000288 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AG8FG UT WOS:000335653600028 PM 24361903 ER PT J AU Kirwan, JR Boers, M Hewlett, S Beaton, D Bingham, CO Choy, E Conaghan, PG D'Agostino, MA Dougados, M Furst, DE Guillemin, F Gossec, L van der Heijde, DM Kloppenburg, M Kvien, TK Landewe, RBM Mackie, SL Matteson, EL Mease, PJ Merkel, PA Ostergaard, M Saketkoo, LA Simon, L Singh, JA Strand, V Tugwell, P AF Kirwan, John R. Boers, Maarten Hewlett, Sarah Beaton, Dorcas Bingham, Clifton O., III Choy, Ernest Conaghan, Philip G. D'Agostino, Maria-Antonietta Dougados, Maxime Furst, Daniel E. Guillemin, Francis Gossec, Laure van der Heijde, Desiree M. Kloppenburg, Margreet Kvien, Tore K. Landewe, Robert B. M. Mackie, Sarah L. Matteson, Eric L. Mease, Philip J. Merkel, Peter A. Ostergaard, Mikkel Saketkoo, Lesley Ann Simon, Lee Singh, Jasvinder A. Strand, Vibeke Tugwell, Peter TI Updating the OMERACT Filter: Core Areas as a Basis for Defining Core Outcome Sets SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OUTCOME MEASURES IN RHEUMATOLOGY; CLINICAL TRIALS; OUTCOME AND PROCESS ASSESSMENT; CONSENSUS DEVELOPMENT CONFERENCE ID RHEUMATOID-ARTHRITIS; PATIENT PERSPECTIVE; INTERNATIONAL PATIENT; FATIGUE; FLARE AB Objective. The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter presupposes an explicit framework for identifying the relevant core outcomes that are universal to all studies of the effects of intervention effects. There is no published outline for instrument choice or development that is aimed at measuring outcome, was derived from broad consensus over its underlying philosophy, or includes a structured and documented critique. Therefore, a new proposal for defining core areas of measurement ("Filter 2.0 Core Areas of Measurement") was presented at OMERACT 11 to explore areas of consensus and to consider whether already endorsed core outcome sets fit into this newly proposed framework. Methods. Discussion groups critically reviewed the extent to which case studies of current OMERACT Working Groups complied with or negated the proposed framework, whether these observations had a more general application, and what issues remained to be resolved. Results. Although there was broad acceptance of the framework in general, several important areas of construction, presentation, and clarity of the framework were questioned. The discussion groups and subsequent feedback highlighted 20 such issues. Conclusion. These issues will require resolution to reach consensus on accepting the proposed Filter 2.0 framework of Core Areas as the basis for the selection of Core Outcome Domains and hence appropriate Core Outcome Sets for clinical trials. C1 [Kirwan, John R.] Univ Bristol, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol, Avon, England. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, Amsterdam, Netherlands. [Hewlett, Sarah] Univ W England, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol BS16 1QY, Avon, England. [Beaton, Dorcas] Univ Toronto, Inst Hlth Policy Management & Evaluat, Dept Occupat Sci & Occupat Therapy, Toronto, ON, Canada. [Bingham, Clifton O., III] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Choy, Ernest] Cardiff Univ, Sch Med, Rheumatol Sect, Cardiff CF10 3AX, S Glam, Wales. [Conaghan, Philip G.] Univ Leeds, Div Musculoskeletal Dis, Leeds, W Yorkshire, England. UK Natl Inst Hlth Res NIHR Leeds Musculoskeletal, Leeds, W Yorkshire, England. [D'Agostino, Maria-Antonietta] Versailles St Quentin Yvelines Univ, Dept Rheumatol, Ambroise Pare Hosp, AP HP, Boulogne, France. [Dougados, Maxime] Paris Descartes Univ, Fac Med, Cochin Hosp, AP HP, Paris, France. [Furst, Daniel E.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. [Guillemin, Francis] Univ Paris 05, Univ Lorraine, Nancy, France. Univ Paris 06, Paris, France. [Gossec, Laure] Hop La Pitie Salpetriere, AP HP, Dept Rheumatol, Paris, France. [van der Heijde, Desiree M.; Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands. [Kvien, Tore K.] Diakonhjemmet Hosp, Dept Rheumatol, Oslo, Norway. [Landewe, Robert B. M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1012 WX Amsterdam, Netherlands. [Landewe, Robert B. M.] Atrium Med Ctr Heerlen, Heerlen, Netherlands. [Mackie, Sarah L.] Univ Leeds, Div Rheumat & Musculoskeletal Dis, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Matteson, Eric L.] Mayo Clin, Coll Med, Div Rheumatol, Rochester, MN USA. Univ Washington, Sch Med, Seattle Rheumatol Associates, Swedish Med Ctr,Rheumatol Res Div, Seattle, WA USA. [Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Ostergaard, Mikkel] Copenhagen Univ Hosp Glostrup, Dept Rheumatol, Copenhagen, Denmark. [Saketkoo, Lesley Ann] Louisiana State Univ, Rheumatol Sect, Hlth Sci Ctr, New Orleans, LA USA. [Simon, Lee] SDG LLC, Cambridge, MA USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. RP Kirwan, JR (reprint author), Univ Bristol, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol, Avon, England. EM john.kirwan@bristol.ac.uk RI DOUGADOS, MAXIME/P-5287-2016; OI Tugwell, Peter/0000-0001-5062-0556; Kirwan, John/0000-0002-6617-3217 FU Novartis; American College of Rheumatology; European League Against Rheumatism;; Takeda pharmaceutical; Savient pharmaceutical; Ardea pharmaceutical; Regeneron pharmaceutical; Allergan pharmaceutical; URL pharmaceutical; Takeda; Savient FX Dr. Matteson is supported in part by grants from Novartis, the American College of Rheumatology, and the European League Against Rheumatism; and was a consultant to Horizon Pharmaceuticals; Dr. Singh received research grants from Takeda and Savient, consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL pharmaceuticals and Novartis; is a member of the OMERACT executive, which receives arms-length funding from 36 companies; and is a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee and the Veterans Affairs Rheumatology Field Advisory Committee. NR 15 TC 10 Z9 10 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2014 VL 41 IS 5 BP 994 EP 999 DI 10.3899/jrheum.131309 PG 6 WC Rheumatology SC Rheumatology GA AG6FN UT WOS:000335514500028 PM 24634204 ER PT J AU Tugwell, P Boers, M D'Agostino, MA Beaton, D Boonen, A Bingham, CO Choy, E Conaghan, PG Dougados, M Duarte, C Furst, DE Guillemin, F Gossec, L Heiberg, T van der Heijde, DM Hewlett, S Kirwan, JR Kvien, TK Landewe, RB Mease, PJ Ostergaard, M Simon, L Singh, JA Strand, V Wells, G AF Tugwell, Peter Boers, Maarten D'Agostino, Maria-Antonietta Beaton, Dorcas Boonen, Annelies Bingham, Clifton O., III Choy, Ernest Conaghan, Philip G. Dougados, Maxime Duarte, Catia Furst, Daniel E. Guillemin, Francis Gossec, Laure Heiberg, Turid van der Heijde, Desiree M. Hewlett, Sarah Kirwan, John R. Kvien, Tore K. Landewe, Robert B. Mease, Philip J. Ostergaard, Mikkel Simon, Lee Singh, Jasvinder A. Strand, Vibeke Wells, George TI Updating the OMERACT Filter: Implications of Filter 2.0 to Select Outcome Instruments Through Assessment of "Truth": Content, Face, and Construct Validity SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OMERACT; RANDOMIZED CONTROLLED TRIALS; OUTCOME AND PROCESS ASSESSMENT; CONSTRUCT VALIDITY; CONTENT VALIDITY; FACE VALIDITY AB Objective. The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter requires that criteria be met to demonstrate that the outcome instrument meets the criteria for content, face, and construct validity. Methods. Discussion groups critically reviewed a variety of ways in which case studies of current OMERACT Working Groups complied with the Truth component of the Filter and what issues remained to be resolved. Results. The case studies showed that there is broad agreement on criteria for meeting the Truth criteria through demonstration of content, face, and construct validity; however, several issues were identified that the Filter Working Group will need to address. Conclusion. These issues will require resolution to reach consensus on how Truth will be assessed for the proposed Filter 2.0 framework, for instruments to be endorsed by OMERACT. C1 [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON K1N 6N5, Canada. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, Amsterdam, Netherlands. [D'Agostino, Maria-Antonietta] Versailles St Quentin Yvelines Univ, Dept Rheumatol, Ambroise Pare Hosp, AP HP, Boulogne, France. [Dougados, Maxime] Paris Descartes Univ, Cochin Hosp, AP HP, Fac Med, Paris, France. [Beaton, Dorcas] Univ Toronto, Inst Hlth Policy Management & Evaluat, Dept Occupat Sci & Occupat Therapy, Toronto, ON, Canada. [Boonen, Annelies] Maastricht Univ, Med Ctr, Dept Internal Med, Div Rheumatol, Maastricht, Netherlands. [Boonen, Annelies] Maastricht Univ, Caphri Res Inst, Maastricht, Netherlands. [Bingham, Clifton O., III] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Choy, Ernest] Cardiff Univ, Rheumatol Sect, Sch Med, Cardiff CF10 3AX, S Glam, Wales. Univ Leeds, Div Musculoskeletal Dis, Leeds LS2 9JT, W Yorkshire, England. UK Natl Inst Hlth Res NIHR Leeds Musculoskeletal, Leeds, W Yorkshire, England. [Duarte, Catia] Ctr Hosp & Univ Coimbra, Dept Rheumatol, Coimbra, Portugal. [Furst, Daniel E.] Univ Calif Los Angeles, Dept Rheumatol, Geffen Sch Med, Los Angeles, CA USA. Univ Lorraine, EA APEMAC 4360, Nancy, France. [Gossec, Laure] Univ Paris 06, Pitie Salpetriere Hosp, AP HP, Dept Rheumatol,GRC UMPC EEMOIS 08, Paris, France. [Heiberg, Turid] Oslo Univ Hosp, Oslo, Norway. [Heiberg, Turid] Lovisenberg Diaconal Univ Coll, Oslo, Norway. [van der Heijde, Desiree M.] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. [Hewlett, Sarah] Univ W England, Acad Rheumatol Unit, Bristol Royal Infirm, Bristol BS16 1QY, Avon, England. [Kvien, Tore K.] Diakonhjemmet Hosp, Dept Rheumatol, Oslo, Norway. [Landewe, Robert B.] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, Heerlen, Netherlands. [Landewe, Robert B.] Atrium Med Ctr Heerlen, Heerlen, Netherlands. [Mease, Philip J.] Seattle Rheumatol Associates, Seattle, WA USA. [Mease, Philip J.] Swedish Med Ctr, Rheumatol Res Div, Seattle, WA USA. [Mease, Philip J.] Univ Washington, Sch Med, Seattle, WA USA. Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Ostergaard, Mikkel] Copenhagen Univ Hosp Glostrup, Dept Rheumatol, Copenhagen, Denmark. [Simon, Lee] SDG LLC, Cambridge, MA USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Immunol Rheumatol, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Wells, George] Univ Ottawa, Dept Epidemiol & Community Med, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. RP Tugwell, P (reprint author), Univ Ottawa, Ctr Global Hlth, Inst Populat Hlth, 1 Stewart St,Room 312, Ottawa, ON K1N 6N5, Canada. EM tugwell.bb@uottawa.ca RI DOUGADOS, MAXIME/P-5287-2016; OI Duarte, Catia/0000-0001-9327-6935; Tugwell, Peter/0000-0001-5062-0556 FU AHRQ HHS [HS013852, HS013852-07]; None [HS013852, HS013852-07] NR 4 TC 13 Z9 13 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2014 VL 41 IS 5 BP 1000 EP 1004 DI 10.3899/jrheum.131310 PG 5 WC Rheumatology SC Rheumatology GA AG6FN UT WOS:000335514500029 PM 24692531 ER PT J AU Wells, G Beaton, DE Tugwell, P Boers, M Kirwan, JR Bingham, CO Boonen, A Brooks, P Conaghan, PG D'Agostino, MA Dougados, M Furst, DE Gossec, L Guillemin, F Helliwell, P Hewlett, S Kvien, TK Landewe, RB March, L Mease, PJ Ostergaard, M Simon, L Singh, JA Strand, V van der Heijde, DM AF Wells, George Beaton, Dorcas E. Tugwell, Peter Boers, Maarten Kirwan, John R. Bingham, Clifton O., III Boonen, Annelies Brooks, Peter Conaghan, Philip G. D'Agostino, Maria-Antonietta Dougados, Maxime Furst, Daniel E. Gossec, Laure Guillemin, Francis Helliwell, Philip Hewlett, Sarah Kvien, Tore K. Landewe, Robert B. March, Lyn Mease, Philip J. Ostergaard, Mikkel Simon, Lee Singh, Jasvinder A. Strand, Vibeke van der Heijde, Desiree M. TI Updating the OMERACT Filter: Discrimination and Feasibility SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE OUTCOME MEASURES IN RHEUMATOLOGY; OUTCOME AND PROCESS ASSESSMENT; FEASIBILITY; DISCRIMINATION ID CLINICALLY IMPORTANT DIFFERENCE; HEALTH-STATUS; QUALITY AB The "Discrimination" part of the OMERACT Filter asks whether a measure discriminates between situations that are of interest. "Feasibility" in the OMERACT Filter encompasses the practical considerations of using an instrument, including its ease of use, time to complete, monetary costs, and interpretability of the question(s) included in the instrument. Both the Discrimination and Reliability parts of the filter have been helpful but were agreed on primarily by consensus of OMERACT participants rather than through explicit evidence-based guidelines. In Filter 2.0 we wanted to improve this definition and provide specific guidance and advice to participants. C1 [Wells, George] Univ Ottawa, Cardiovasc Res Methods Ctr, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON K1H 8M5, Canada. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, Amsterdam, Netherlands. [Kirwan, John R.] Univ Bristol, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol, Avon, England. [Beaton, Dorcas E.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Dept Occupat Sci & Occupat Therapy, Toronto, ON, Canada. [Bingham, Clifton O., III] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Boonen, Annelies] Maastricht Univ, Dept Internal Med, Div Rheumatol, Med Ctr, Maastricht, Netherlands. [Boonen, Annelies] Maastricht Univ, Caphri Res Inst, Maastricht, Netherlands. [Brooks, Peter] Univ Melbourne, Sch Populat Hlth, AHWI, Melbourne, Vic, Australia. [Conaghan, Philip G.] Univ Leeds, Div Musculoskeletal Dis, Leeds, W Yorkshire, England. UK Natl Inst Hlth Res NIHR, Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [D'Agostino, Maria-Antonietta] Versailles St Quentin Yvelines Univ, Dept Rheumatol, Ambroise Pare Hosp, AP HP, Boulogne, France. [Dougados, Maxime] Paris Descartes Univ, Cochin Hosp, AP HP, Fac Med, Paris, France. Cardiff Univ, Sch Med, Rheumatol Sect, Cardiff CF10 3AX, S Glam, Wales. [Furst, Daniel E.] Univ Calif Los Angeles, Geffen Sch Med, Dept Rheumatol, Los Angeles, CA USA. [Gossec, Laure] Univ Paris 06, Pitie Salpetriere Hosp, AP HP, Dept Rheumatol,GRC UMPC EEMOIS 08, Paris, France. [Guillemin, Francis] Univ Paris 05, Univ Lorraine, Nancy, France. [Helliwell, Philip] Univ Leeds, Sect Musculoskeletal Dis, LIMM Chapel Allerton Hosp, Leeds, W Yorkshire, England. [Hewlett, Sarah] Univ W England, Acad Rheumatol Unit, Bristol Royal Infirm, Bristol BS16 1QY, Avon, England. [Kvien, Tore K.] Diakonhjemmet Hosp, Dept Rheumatol, Oslo, Norway. [Landewe, Robert B.] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1012 WX Amsterdam, Netherlands. [Landewe, Robert B.] Atrium Med Ctr Heerlen, Heerlen, Netherlands. Univ Sydney, Inst Bone & Joint Res, Sydney Med Sch, Sydney, NSW 2006, Australia. [March, Lyn] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [March, Lyn] Royal North Shore, Dept Rheumatol, St Leonards, NSW, Australia. Univ Washington, Sch Med, Seattle Rheumatol Associates, Swedish Med Ctr,Rheumatol Res Div, Seattle, WA USA. [Ostergaard, Mikkel] Copenhagen Univ Hosp Glostrup, Dept Rheumatol, Glostrup, Denmark. [Simon, Lee] SDG LLC, Cambridge, MA USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Immunol Rheumatol, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [van der Heijde, Desiree M.] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. RP Wells, G (reprint author), Univ Ottawa, 40 Ruskin St, Ottawa, ON K1H 8M5, Canada. EM gawells@ottawaheart.ca RI DOUGADOS, MAXIME/P-5287-2016; OI Tugwell, Peter/0000-0001-5062-0556 FU AHRQ HHS [HS013852, HS013852-07]; None [HS013852, HS013852-07] NR 17 TC 8 Z9 8 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2014 VL 41 IS 5 BP 1005 EP 1010 DI 10.3899/jrheum.131311 PG 6 WC Rheumatology SC Rheumatology GA AG6FN UT WOS:000335514500030 PM 24692522 ER PT J AU D'Agostino, MA Boers, M Kirwan, J van der Heijde, D Ostergaard, M Schett, G Landewe, RB Maksymowych, WP Naredo, E Dougados, M Iagnocco, A Bingham, CO Brooks, PM Beaton, DE Gandjbakhch, F Gossec, L Guillemin, F Hewlett, SE Kloppenburg, M March, L Mease, PJ Moller, I Simon, LS Singh, JA Strand, V Wakefield, RJ Wells, GA Tugwell, P Conaghan, PG AF D'Agostino, Maria-Antonietta Boers, Maarten Kirwan, John van der Heijde, Desiree Ostergaard, Mikkel Schett, Georg Landewe, Robert B. Maksymowych, Walter P. Naredo, Esperanza Dougados, Maxime Iagnocco, Annamaria Bingham, Clifton O., III Brooks, Peter M. Beaton, Dorcas E. Gandjbakhch, Frederique Gossec, Laure Guillemin, Francis Hewlett, Sarah E. Kloppenburg, Margreet March, Lyn Mease, Philip J. Moller, Ingrid Simon, Lee S. Singh, Jasvinder A. Strand, Vibeke Wakefield, Richard J. Wells, George A. Tugwell, Peter Conaghan, Philip G. TI Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE BIOMARKERS; IMAGING; OUTCOME AND PROCESS ASSESSMENT; OMERACT FILTER; VALIDATION FRAMEWORK ID EARLY RHEUMATOID-ARTHRITIS; SPONDYLOARTHRITIS RESEARCH CONSORTIUM; SACROILIAC JOINT INFLAMMATION; POWER DOPPLER ULTRASONOGRAPHY; PAINFUL KNEE OSTEOARTHRITIS; RANDOMIZED CONTROLLED-TRIAL; ULTRASOUND TASK-FORCE; ACUTE-PHASE RESPONSE; DAMAGE END-POINTS; ANKYLOSING-SPONDYLITIS AB Objective. The Outcome Measures in Rheumatology (OMERACT) Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges because of their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment. Methods. A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting, and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient-centered or disease-centered variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondy-loarthritis, and knee osteoarthritis were then evaluated using the original OMERACT Filter and the newly proposed structure. Breakout groups critically reviewed the extent to which the candidate biomarkers complied with the proposed stepwise approach, as a way of examining the utility of the proposed 3-dimensional structure. Results. Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials. Conclusion. General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0. C1 [D'Agostino, Maria-Antonietta] Versailles St Quentin Yvelines Univ, Dept Rheumatol, Ambroise Pare Hosp, AP HP, Boulogne, France. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Dept Rheumatol, Amsterdam, Netherlands. [Kirwan, John] Univ Bristol, Acad Rheumatol Unit, Bristol Royal Infirm, Bristol, Avon, England. [van der Heijde, Desiree; Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. [Ostergaard, Mikkel] Copenhagen Univ Hosp Glostrup, Copenhagen Ctr Arthrit Res, Ctr Rheumatol & Spine Dis, Copenhagen, Denmark. [Schett, Georg] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. [Schett, Georg] Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany. [Landewe, Robert B.] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. [Landewe, Robert B.] Atrium Med Ctr, Amsterdam, Netherlands. [Maksymowych, Walter P.] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Naredo, Esperanza] Hosp Gen Gregorio Maranon, Dept Rheumatol, Madrid, Spain. [Dougados, Maxime] Paris Descartes Univ, Fac Med, Cochin Hosp, AP HP, Paris, France. [Iagnocco, Annamaria] Univ Roma La Sapienza, Rheumatol Unit, I-00185 Rome, Italy. [Bingham, Clifton O., III] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Brooks, Peter M.] Univ Melbourne, Melbourne, Vic, Australia. St Michaels Hosp, Mobil Program Clin Res Unit, Toronto, ON M5B 1W8, Canada. Inst Work & Hlth, Toronto, ON, Canada. Univ Toronto, Dept Hlth Policy Management & Evaluat, Dept Rehabil Sci, Toronto, ON, Canada. Dept Occupat Sci & Occupat Therapy, Toronto, ON, Canada. [Gossec, Laure] Univ Paris 06, Pitie Salpetriere Hosp, AP HP, Dept Rheumatol,GRC UPMC EEMOIS 08, Paris, France. [Guillemin, Francis] Univ Paris 05, Univ Lorraine, EA APEMAC 4360, Nancy, France. [Guillemin, Francis] CHU Nancy, Inserm CIC EC, Nancy, France. [Hewlett, Sarah E.] Univ W England, Dept Nursing, Bristol BS16 1QY, Avon, England. [Mease, Philip J.] Swedish Med Ctr, Seattle, WA USA. [Mease, Philip J.] Univ Washington, Seattle, WA 98195 USA. [Moller, Ingrid] Inst Poal, Barcelona, Spain. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Wakefield, Richard J.; Conaghan, Philip G.] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England. UK Natl Inst Hlth Res, Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. RP D'Agostino, MA (reprint author), Hop Ambroise Pare, AP HP, Dept Rheumatol, 9 Ave Charles de Gaulle, F-92100 Boulogne, France. EM maria-antonietta.dagostino@apr.aphp.fr RI DOUGADOS, MAXIME/P-5287-2016; OI Tugwell, Peter/0000-0001-5062-0556 FU AHRQ HHS [HS013852, HS013852-07]; None [HS013852, HS013852-07] NR 79 TC 5 Z9 5 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2014 VL 41 IS 5 BP 1016 EP 1024 DI 10.3899/jrheum.131313 PG 9 WC Rheumatology SC Rheumatology GA AG6FN UT WOS:000335514500032 PM 24584916 ER PT J AU Sartor, CE Kranzler, HR Gelernter, J AF Sartor, Carolyn E. Kranzler, Henry R. Gelernter, Joel TI Characteristics and Course of Dependence in Cocaine-Dependent Individuals Who Never Used Alcohol or Marijuana or Used Cocaine First SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID DRUG-USE; SUBSTANCE USE; SEMISTRUCTURED ASSESSMENT; GATEWAY HYPOTHESIS; INITIATION; SEQUENCE; ADOLESCENTS; CANNABIS; ASSOCIATIONS; COMORBIDITY AB Objective: Cocaine users typically try alcohol or marijuana before cocaine, but this ordering of substance use initiation is not universal. Characterizing cocaine-dependent users who deviate from the typical sequence may be informative for understanding the multiple pathways to cocaine dependence. Method: Data were drawn from cocaine-dependent participants (N=6,333; 41% female) in a multisite study of the genetics of substance dependence who completed in-person structured psychiatric interviews. Participants were categorized with respect to alcohol or marijuana use as (a) never used, (b) used cocaine first, or (c) first used at the same age as or after first cocaine use. The association of a range of demographic, psychiatric, and childhood risk factors with sequences of initiation and the association of those sequences with indicators of dependence course (e.g., severity) were investigated in a series of regression analyses. Results: Women and non-European Americans were overrepresented in the atypical sequence groups. The atypical sequence groups also differed from the typical sequence groups with respect to rates of other substance use disorders. Sequences of substance use initiation were largely unrelated to other psychiatric disorders or childhood risk factors. Individuals who never used marijuana had a lower severity of dependence. Conclusions: Although only a minority of dependent cocaine users deviate from the typical sequence of substance use initiation, several characteristics distinguish them from those who follow the typical sequence. Findings underscore the diversity in pathways to cocaine dependence. C1 [Sartor, Carolyn E.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia Vet Affairs Med Ctr, Vet Integrated Serv Network 4, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, West Haven, CT 06516 USA. RP Sartor, CE (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, 950 Campbell Ave 151D, West Haven, CT 06516 USA. EM carolyn.sartor@yale.edu FU National Institutes of Health [AA017921, DA12849, DA12690, AA11330, AA13736]; Veterans Affairs (VA) Connecticut; Philadelphia VA Mental Illness Research, Education, and Clinical Centers (MIRECCs) FX This work was supported by National Institutes of Health Grants AA017921, DA12849, DA12690, AA11330, and AA13736 and the Veterans Affairs (VA) Connecticut and Philadelphia VA Mental Illness Research, Education, and Clinical Centers (MIRECCs). NR 20 TC 3 Z9 3 U1 2 U2 4 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 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2014 VL 75 IS 3 BP 423 EP 427 PG 5 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA AG7WY UT WOS:000335630700007 PM 24766754 ER PT J AU Rolland, Y Resnick, B Katz, PR Little, MO Ouslander, JG Bonner, A Geary, CR Schumacher, KL Thompson, S Martin, FC Wilbers, J Zuniga, F Ausserhofer, D Schwendimann, R Schussler, S Dassen, T Lohrmann, C Levy, C Whitfield, E Barreto, PD Etherton-Beer, C Dilles, T Azermai, M Bourgeois, J Orrell, M Grossberg, GT Kergoat, H Thomas, DR Visschedijk, J Taylor, SJC Handajani, YS Widjaja, NT Turana, Y Rantz, MJ Skubic, M Morley, JE AF Rolland, Yves Resnick, Barbara Katz, Paul R. Little, Milta O. Ouslander, Joseph G. Bonner, Alice Geary, Carol R. Schumacher, Karen L. Thompson, Sarah Martin, Finbarr C. Wilbers, Joachim Zuniga, Franziska Ausserhofer, D. Schwendimann, R. Schuessler, S. Dassen, Theo Lohrmann, Christa Levy, Cari Whitfield, Emily Barreto, Philipe de Souto Etherton-Beer, Christopher Dilles, Tinne Azermai, Majda Bourgeois, Jolyce Orrell, Martin Grossberg, George T. Kergoat, Helene Thomas, David R. Visschedijk, Jan Taylor, Stephanie J. C. Handajani, Yvonne S. Widjaja, Nelly T. Turana, Yuda Rantz, Marilyn J. Skubic, Marjorie Morley, John E. CA OPERA Study Team TI Nursing Home Research: The First International Association of Gerontology and Geriatrics (IAGG) Research Conference SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Research in long-term care; nursing home research; physician practice; transitions; quality improvement; European nursing homes; medical foster home; culture change; Pharmanurse; psychotropic drugs; cognitive stimulus therapy; depression in the nursing home; pressure ulcers; fear of falling; exercise intervention; homecare; technological nursing home; eye care in the nursing home ID POTENTIALLY AVOIDABLE HOSPITALIZATIONS; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM-CARE; MEDICAL STAFF ORGANIZATION; QUALITY-OF-LIFE; MDS 3.0; EXERCISE INTERVENTION; RESIDENTIAL CARE; OLDER PERSONS; OPERA TRIAL AB The International Association of Gerontology and Geriatrics held its first conference on nursing home research in St Louis, MO, in November 2013. This article provides a summary of the presentations. (C) 2014 - American Medical Directors Association, Inc. All rights reserved. C1 [Rolland, Yves; Barreto, Philipe de Souto] Gerontopole, Toulouse, France. [Resnick, Barbara] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Katz, Paul R.] Univ Toronto, Baycrest Hlth Ctr, Toronto, ON, Canada. [Little, Milta O.; Morley, John E.] St Louis Univ, Sch Med, Div Geriatr Med, St Louis, MO 63104 USA. [Ouslander, Joseph G.] Florida Atlantic Univ, Charles E Schmidt Coll Med, Geriatr Programs, Boca Raton, FL 33431 USA. [Bonner, Alice] Northeastern Univ, Sch Nursing, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Geary, Carol R.; Schumacher, Karen L.] Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA. [Thompson, Sarah] Univ Colorado, Coll Nursing, Denver, CO 80202 USA. [Martin, Finbarr C.] Guys & St Thomas NHS Trust, London, England. [Martin, Finbarr C.] Kings Coll London, London, England. [Wilbers, Joachim] ProjectCare, Frankfurt, Germany. [Zuniga, Franziska; Ausserhofer, D.; Schwendimann, R.] Univ Basel, Inst Nursing Sci, Basel, Switzerland. [Schuessler, S.; Lohrmann, Christa] Med Univ Graz, Inst Nursing Sci, Graz, Austria. [Dassen, Theo] Charite, Inst Hlth Sci Educ & Nursing Sci, D-13353 Berlin, Germany. [Levy, Cari; Whitfield, Emily] Denver Vet Affairs Med Ctr, Denver, CO USA. [Levy, Cari] Univ Colorado, Sch Med, Aurora, CO USA. [Etherton-Beer, Christopher] Univ Western Australia, Western Australian Ctr Hlth & Ageing, Crawley, WA, Australia. [Etherton-Beer, Christopher] Royal Perth Hosp, Perth, WA 6001, Australia. [Dilles, Tinne] Univ Antwerp, Ctr Res & Innovat Care, B-2020 Antwerp, Belgium. [Dilles, Tinne] Thomas More Univ Coll, Lier, Belgium. [Azermai, Majda; Bourgeois, Jolyce; Orrell, Martin] Univ Ghent, Heymans Inst Pharmacol, Clin Pharmacol Res Unit, B-9000 Ghent, Belgium. [Orrell, Martin] UCL, London, England. [Grossberg, George T.] St Louis Univ, Div Geriatr Psychiat, Dept Neurol & Psychiat, St Louis, MO 63104 USA. [Kergoat, Helene] Univ Montreal, Ecole Optometrie, Montreal, PQ, Canada. [Kergoat, Helene] Inst Univ Geriatrie Montreal, Montreal, PQ, Canada. [Visschedijk, Jan] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands. [Taylor, Stephanie J. C.] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Primary Care & Publ Hlth, Blizard Inst, London, England. [Handajani, Yvonne S.; Widjaja, Nelly T.] Atma Jaya Catholic Univ, Sch Med, Ctr Hlth Res, Dept Publ Hlth, Jakarta, Indonesia. [Turana, Yuda] Atma Jaya Catholic Univ, Sch Med, Ctr Hlth Res, Dept Neurol, Jakarta, Indonesia. [Rantz, Marilyn J.] Univ Missouri, Sinclair Sch Nursing, Aging Pl Project, Columbia, MO USA. [Skubic, Marjorie] Univ Missouri, Ctr Eldercare & Rehabil Technol, Columbia, MO USA. RP Morley, JE (reprint author), St Louis Univ, Sch Med, Div Geriatr Med, 1402 S Grand Blvd,M238, St Louis, MO 63104 USA. EM morley@slu.edu RI Etherton-Beer, Christopher/B-2714-2014; Dilles, Tinne/F-3393-2013; OI Etherton-Beer, Christopher/0000-0001-5148-0188; Dilles, Tinne/0000-0003-2817-0944; Zuniga, Franziska/0000-0002-8844-4903; Taylor, Stephanie/0000-0001-7454-6354; Lohrmann, Christa/0000-0002-0778-5854 FU National Institute of Nursing Research of the National Institutes of Health [1F31NR013596-01A1]; Fondation Caroline-Durand; Canadian National Institute for the Blind; Societe Alzheimer du Canada; National Institute for Health Research Health Technology Assessment Programme UK [01/02/01] FX The research for Methodology for Study of Care Transitions (CRG, KLS, ST) was supported by National Institute of Nursing Research of the National Institutes of Health under award number 1F31NR013596-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Vision in Older Institutionalized Individuals (HK) was funded by Fondation Caroline-Durand, Canadian National Institute for the Blind, Societe Alzheimer du Canada.; The OPERA project (SJCT) was funded by the National Institute for Health Research Health Technology Assessment Programme UK (project no. 01/02/01). The sponsors of the study played no part in the preparation of this paper. The views and opinions expressed here are those of the authors and do not necessarily reflect those of the Health Technology Assessment Programme, the National Institute for Health Research, or the Department of Health. NR 88 TC 14 Z9 14 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAY PY 2014 VL 15 IS 5 BP 313 EP 325 DI 10.1016/j.jamda.2014.03.004 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AG5DF UT WOS:000335438700004 PM 24767432 ER PT J AU Ting, B Zurakowski, D Herder, L Wagner, K Appleton, P Rodriguez, EK AF Ting, Beverlie Zurakowski, David Herder, Lindsay Wagner, Katiri Appleton, Paul Rodriguez, Edward K. TI Preinjury ambulatory status is associated with 1-year mortality following lateral compression Type I fractures in the geriatric population older than 80 years SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Geriatric; pelvic fracture; LC-1 ID HIP FRACTURE; PELVIC FRACTURE; PUBIC RAMI; EPIDEMIOLOGY; OUTCOMES; PEOPLE; WOMEN AB BACKGROUND: Lateral compression pelvic Type I fractures in the elderly population are most often low-energy osteoporosis related fractures. Previous literature comparing pelvic fractures in young versus elderly patients called into question the general consideration of these injuries as benign injuries with favorable prognoses; however, the geriatric population older than 80 years is often underrepresented. This article focuses on the mortality and functional outcomes after low-energy pelvic fractures in a population of patients older than 80 years. METHODS: We prescreened potential subjects in a Level I trauma institution's electronic medical record database between January 1, 2002, and April 30, 2012, to identify isolated lateral compression Type 1 fractures treated nonoperatively in patients older than 80 years. This study was composed of a retrospective review of medical records followed by a prospective survey data collection to examine mechanisms of injury, length of hospital stay, complications, medical comorbidities, ambulatory function, living situation, pain, and 1 year mortality rates. RESULTS: We present a large case series of 85 patients older than 80 years and report a 1-year mortality rate of 20%. We found that patients who were household ambulators or nonfunctional ambulators were five times more likely (24.4% vs. 6.1%) to die within 1 year after injury. Multivariate logistic regression confirmed that the risk of 1-year mortality was significantly higher for household-bound patients compared with community ambulators, independent of sex, smoking, Charlson comorbidity index, or length of hospital stay. CONCLUSION: This is the first study to demonstrate a difference in 1-year mortality between patients who were community ambulators versus those who were household ambulators or nonfunctional ambulators before injury. With our aging population, these findings have important implications. Maintenance of general conditioning and early mobilization with physical therapy after injury is a key part of geriatric orthopedic rehabilitation. (J Trauma Acute Care Surg. 2014; 76: 1306-1309. Copyright (C) 2014 by Lippincott Williams & Wilkins) C1 [Ting, Beverlie] Massachusetts Gen Hosp, Harvard Combined Orthoped Residency Program, Boston, MA 02114 USA. [Zurakowski, David] Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Herder, Lindsay; Wagner, Katiri; Appleton, Paul; Rodriguez, Edward K.] Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA. RP Rodriguez, EK (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Stoneman 10, Boston, MA 02215 USA. EM ekrodrig@bidmc.harvard.edu NR 19 TC 2 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAY PY 2014 VL 76 IS 5 BP 1306 EP 1309 DI 10.1097/TA.0000000000000212 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AG6YA UT WOS:000335563800028 PM 24747465 ER PT J AU Niewczas, MA Sirich, TL Mathew, AV Skupien, J Mohney, RP Warram, JH Smiles, A Huang, XP Walker, W Byun, J Karoly, ED Kensicki, EM Berry, GT Bonventre, JV Pennathur, S Meyer, TW Krolewski, AS AF Niewczas, Monika A. Sirich, Tammy L. Mathew, Anna V. Skupien, Jan Mohney, Robert P. Warram, James H. Smiles, Adam Huang, Xiaoping Walker, Walker Byun, Jaeman Karoly, Edward D. Kensicki, Elizabeth M. Berry, Gerard T. Bonventre, Joseph V. Pennathur, Subramaniam Meyer, Timothy W. Krolewski, Andrzej S. TI Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study SO KIDNEY INTERNATIONAL LA English DT Article ID PROTEIN C-MANNOSYLATION; PROXIMAL TUBULAR CELLS; CHRONIC KIDNEY-DISEASE; AMINO-ACID-TRANSPORT; D-CHIRO-INOSITOL; MYOINOSITOL OXYGENASE; MASS-SPECTROMETRY; MOLECULAR-CLONING; TOXINS; SERUM AB Here we studied plasma metabolomic profiles as determinants of progression to end-stage renal disease (ESRD) in patients with type 2 diabetes (T2D). This nested case-control study evaluated 40 cases who progressed to ESRD during 8-12 years of follow-up and 40 controls who remained alive without ESRD from the Joslin Kidney Study cohort. Controls were matched with cases for baseline clinical characteristics, although controls had slightly higher eGFR and lower levels of urinary albumin excretion than cases. Plasma metabolites at baseline were measured by mass spectrometry-based global metabolomic profiling. Of the named metabolites in the library, 262 were detected in at least 80% of the study patients. The metabolomic platform recognized 78 metabolites previously reported to be elevated in ESRD (uremic solutes). Sixteen were already elevated in the baseline plasma of our cases years before ESRD developed. Other uremic solutes were either not different or not commonly detectable. Essential amino acids and their derivatives were significantly depleted in the cases, whereas certain amino acid-derived acylcarnitines were increased. All findings remained statistically significant after adjustment for differences between study groups in albumin excretion rate, eGFR, or HbAlc. Uremic solute differences were confirmed by quantitative measurements. Thus, abnormal plasma concentrations of putative uremic solutes and essential amino acids either contribute to progression to ESRD or are a manifestation of an early stage(s) of the disease process that leads to ESRD in T2D. C1 [Niewczas, Monika A.; Skupien, Jan; Warram, James H.; Smiles, Adam; Walker, Walker; Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. [Niewczas, Monika A.; Skupien, Jan; Warram, James H.; Berry, Gerard T.; Bonventre, Joseph V.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sirich, Tammy L.; Meyer, Timothy W.] Stanford Sch Med, Dept Med, Div Renal, Stanford, CA USA. [Mathew, Anna V.; Byun, Jaeman; Pennathur, Subramaniam] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Skupien, Jan] Jagiellonian Univ, Dept Metab Dis, Krakow, Poland. [Mohney, Robert P.; Karoly, Edward D.; Kensicki, Elizabeth M.] Metabolon Inc, Durham, NC USA. [Huang, Xiaoping; Berry, Gerard T.] Boston Childrens Hosp, Metab Program, Boston, MA USA. [Bonventre, Joseph V.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Niewczas, MA (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, One Joslin Pl, Boston, MA 02215 USA. EM monika.niewczas@joslin.harvard.edu OI Berry, Gerard/0000-0001-5299-3313; Mathew, Anna/0000-0002-7043-4221 FU National Institutes of Health (NIH): Diabetes Research Center-Joslin, Pilot and Feasibility Grant [P30DK036836, DK41526, DK67638, DK39773, DK 72381, DK94292, DK89503, DK097153, DK84439, DK80123]; Mitsubishi Tanabe Pharma Corporation NKF Fellowship for the Study of Uremia; JDRF Fellowship Grant [3-2009-397] FX This study was supported by grants from the National Institutes of Health (NIH): Diabetes Research Center-Joslin, Pilot and Feasibility Grant, P30DK036836 to MAN; DK41526 and DK67638 to ASK; DK39773 and DK 72381 to JVB; DK94292, DK89503, and DK097153 to SP; and DK84439 and DK80123 to TWM. TLS was supported by the Mitsubishi Tanabe Pharma Corporation NKF Fellowship for the Study of Uremia, and JS by the JDRF Fellowship Grant 3-2009-397. NR 77 TC 33 Z9 33 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2014 VL 85 IS 5 BP 1214 EP 1224 DI 10.1038/ki.2013.497 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AG9BJ UT WOS:000335713300030 PM 24429397 ER PT J AU Tombal, B Borre, M Rathenborg, P Werbrouck, P Van Poppel, H Heidenreich, A Iversen, P Braeckman, J Heracek, J Baskin-Bey, E Ouatas, TK Perabo, F Phung, D Hirmand, M Smith, MR AF Tombal, Bertrand Borre, Michael Rathenborg, Per Werbrouck, Patrick Van Poppel, Hendrik Heidenreich, Axel Iversen, Peter Braeckman, Johan Heracek, Jiri Baskin-Bey, Edwina Ouatas, Taoufi K. Perabo, Frank De Phung Hirmand, Mohammad Smith, Matthew R. TI Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study SO LANCET ONCOLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; BODY-COMPOSITION; 2ND-GENERATION ANTIANDROGEN; BICALUTAMIDE MONOTHERAPY; CLINICAL-TRIALS; FOLLOW-UP; CASTRATION; EFFICACY AB Background The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. Methods This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. Findings 67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. Interpretation Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer. C1 [Tombal, Bertrand] Catholic Univ Louvain, Inst Rech Clin, B-1200 Brussels, Belgium. [Borre, Michael] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Rathenborg, Per] Herlev Hosp, DK-2730 Herlev, Denmark. [Werbrouck, Patrick] AZ Groeninge Kortrijk, Kortrijk, Belgium. [Van Poppel, Hendrik] UZ Leuven, Louvain, Belgium. [Heidenreich, Axel] Rhein Westfal TH Aachen, Klin & Poliklin Urol, Aachen, Germany. [Iversen, Peter] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. [Braeckman, Johan] UZ Brussel, Brussels, Belgium. [Heracek, Jiri] Charles Univ Prague, Prague, Czech Republic. [Baskin-Bey, Edwina; Ouatas, Taoufi K.; De Phung] Astellas Pharma Global Dev, Leiden, Netherlands. [Perabo, Frank] Astellas Pharma Global Dev, Northbrook, IL USA. [Hirmand, Mohammad] Medivation Inc, San Francisco, CA USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tombal, B (reprint author), Catholic Univ Louvain, Clin Univ St Luc, Inst Rech Clin, Ave Hippocrate 10, B-1200 Brussels, Belgium. EM bertrand.tombal@uclouvain.be FU Astellas; Tanya Chaudry (Complete HealthVizion); National Institute of Health K24 Midcareer Investigator Award [K24 CA121990]; Medivation FX The study was sponsored by Astellas and Medivation. Medical writing assistance, supported financially by Astellas and Medivation, was provided by Tanya Chaudry (Complete HealthVizion) under the authors' conceptual direction and was based on feedback from all authors. MRS is supported by a National Institute of Health K24 Midcareer Investigator Award (K24 CA121990) and a competitive research award from the Prostate Cancer Foundation. NR 32 TC 26 Z9 26 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2014 VL 15 IS 6 BP 592 EP 600 DI 10.1016/S1470-2045(14)70129-9 PG 9 WC Oncology SC Oncology GA AG6ES UT WOS:000335512100046 PM 24739897 ER PT J AU Almagro, JC Gilliland, GL Breden, F Scott, JK Sok, D Pauthner, M Reichert, JM Helguera, G Andrabi, R Mabry, R Blery, M Voss, JE Lauren, J Abuqayyas, L Barghorn, S Ben-Jacob, E Crowe, JE Huston, JS Johnston, SA Krauland, E Lund-Johansen, F Marasco, WA Parren, PWHI Xu, KY AF Almagro, Juan Carlos Gilliland, Gary L. Breden, Felix Scott, Jamie K. Sok, Devin Pauthner, Matthias Reichert, Janice M. Helguera, Gustavo Andrabi, Raiees Mabry, Robert Blery, Mathieu Voss, James E. Lauren, Juha Abuqayyas, Lubna Barghorn, Stefan Ben-Jacob, Eshel Crowe, James E., Jr. Huston, James S. Johnston, Stephen Albert Krauland, Eric Lund-Johansen, Fridtjof Marasco, Wayne A. Parren, Paul W. H. I. Xu, Kai Y. TI Antibody Engineering & Therapeutics, The Annual Meeting of The Antibody Society SO MABS LA English DT Article DE antibody therapeutics; antibody-drug conjugate; bispecific antibodies; protein scaffolds ID BROADLY NEUTRALIZING ANTIBODIES; CHRONIC LYMPHOCYTIC-LEUKEMIA; RABBIT IMMUNOGLOBULIN-G; PROTEIN-COUPLED RECEPTOR; IN-VIVO; MONOCLONAL-ANTIBODIES; DIRECTED EVOLUTION; T-CELLS; B-CELLS; HIV-1-NEUTRALIZING ANTIBODIES AB The 24(th) Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. C1 [Almagro, Juan Carlos] Pfizer, CTI Boston, Boston, MA USA. [Gilliland, Gary L.] Janssen Res & Dev LLC, Spring House, PA USA. [Breden, Felix; Scott, Jamie K.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Sok, Devin; Pauthner, Matthias; Andrabi, Raiees; Voss, James E.] Scripps Res Inst, La Jolla, CA 92037 USA. [Reichert, Janice M.] Reichert Biotechnol Consulting LLC, Framingham, MA 01701 USA. [Helguera, Gustavo] IBYME, Inst Biol Med & Expt, Lab Biotecnol Farmaceut, CONICET, Buenos Aires, DF, Argentina. [Mabry, Robert; Krauland, Eric] Adimab LLC, Lebanon, NH USA. [Blery, Mathieu] Innate Pharma, Marseille, France. [Lauren, Juha] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Abuqayyas, Lubna] Amgen Inc, Thousand Oaks, CA USA. [Barghorn, Stefan] AbbVie, Ludwigshafen, Germany. [Ben-Jacob, Eshel] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Huston, James S.] Huston BioConsulting LLC, Newton, MA USA. [Johnston, Stephen Albert] Arizona State Univ, Phoenix, AZ USA. [Lund-Johansen, Fridtjof] Oslo Univ Hosp, Oslo, Norway. [Marasco, Wayne A.] Dana Farber Canc Ctr, Boston, MA USA. [Parren, Paul W. H. I.] Genmab, Utrecht, Netherlands. [Xu, Kai Y.] Univ Maryland, Baltimore, MD 21201 USA. RP Reichert, JM (reprint author), Reichert Biotechnol Consulting LLC, Framingham, MA 01701 USA. EM reichert.biotechconsulting@gmail.com RI Crowe, James/B-5549-2009; OI Crowe, James/0000-0002-0049-1079; Helguera, Gustavo/0000-0003-1509-3564; Reichert, Janice/0000-0003-0400-1951; Parren, Paul/0000-0002-4365-3859 FU NIAID NIH HHS [R21 AI076176] NR 158 TC 1 Z9 1 U1 2 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD MAY 1 PY 2014 VL 6 IS 3 BP 577 EP 618 DI 10.4161/mabs.28421 PG 42 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG4JC UT WOS:000335384800001 PM 24589717 ER PT J AU Ling, XH Han, ZD Xia, D He, HC Jiang, FN Lin, ZY Fu, X Deng, YH Dai, QS Cai, C Chen, JH Liang, YX Zhong, WD Wu, CL AF Ling, Xiao-hui Han, Zhao-dong Xia, Dan He, Hui-chan Jiang, Fu-neng Lin, Zhuo-yuan Fu, Xin Deng, Ye-han Dai, Qi-shan Cai, Chao Chen, Jia-hong Liang, Yu-xiang Zhong, Wei-de Wu, Chin-lee TI MicroRNA-30c serves as an independent biochemical recurrence predictor and potential tumor suppressor for prostate cancer SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE Prostate cancer; miR-30c; Tumor suppressor; Biochemical recurrence; Prognosis ID EXPRESSION PROFILE; CELLS; PROGRESSION; MIRNAS; CARCINOMA; REVEALS AB MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P < 0.05). In addition, the downregulation of miR-30c in PCa tissues was significantly associated with higher Gleason score (P = 0.009), advanced pathological stage (P = 0.016) and biochemical recurrence (P = 0.034). Moreover, Kaplan-Meier survival analysis showed that the reduced expression of miR-30c was correlated with shorter biochemical recurrence-free survival (P = 0.023). The multivariate analysis also identified miR-30c as an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation, migration and invasion of PCa cells in vitro. Our data indicated the involvement of miR-30c in PCa progression and suggested its potential role as an independent predictor of biochemical recurrence in PCa. On cellular level, miR-30c may function as a tumor suppressor for PCa cells by inhibiting tumor cell proliferation, migration and invasion. C1 [Ling, Xiao-hui; Han, Zhao-dong; He, Hui-chan; Jiang, Fu-neng; Lin, Zhuo-yuan; Fu, Xin; Deng, Ye-han; Dai, Qi-shan; Cai, Chao; Chen, Jia-hong; Liang, Yu-xiang; Zhong, Wei-de] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Guangdong Key Lab Clin Mol Med & Diagnost, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. [Ling, Xiao-hui; Cai, Chao; Zhong, Wei-de] Southern Med Univ, Guangdong Prov Inst Nephrol, Guangzhou 510515, Guangdong, Peoples R China. [Xia, Dan] Zhejiang Univ, Dept Urol, Coll Med, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China. [Wu, Chin-lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Chin-lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Chin-lee] Harvard Univ, Sch Med, Boston, MA USA. RP Zhong, WD (reprint author), Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Guangdong Key Lab Clin Mol Med & Diagnost, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. EM zhongwd2009@live.cn OI Zhong, Weide/0000-0002-0430-2845 FU Key Personnel Plan of Zhejiang Province Medical and Health Platform (Class A) [2011RCA019]; National Natural Science Foundation of China [81170699, 81272813, 81200550]; Science and Technology Project of Guangdong Province [2012B031800008]; Medical Research Fund of Guangdong Province [A2012489]; Guangzhou Municipal Science and Technology Key Project [11C23150711]; Key Projects of Bureau of Health in Guangzhou Municipality [201102A212015] FX This work was supported by grants from Key Personnel Plan of Zhejiang Province Medical and Health Platform (Class A) (2011RCA019), National Natural Science Foundation of China (81170699, 81272813, 81200550), Science and Technology Project of Guangdong Province (2012B031800008), Medical Research Fund of Guangdong Province (A2012489), Guangzhou Municipal Science and Technology Key Project (11C23150711), Key Projects of Bureau of Health in Guangzhou Municipality (201102A212015). NR 40 TC 8 Z9 9 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD MAY PY 2014 VL 41 IS 5 BP 2779 EP 2788 DI 10.1007/s11033-014-3132-7 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG9JC UT WOS:000335734400009 PM 24452717 ER PT J AU Kolacinska, A Morawiec, J Fendler, W Malachowska, B Morawiec, Z Szemraj, J Pawlowska, Z Chowdhury, D Choi, YE Kubiak, R Pakula, L Zawlik, I AF Kolacinska, Agnieszka Morawiec, Jan Fendler, Wojciech Malachowska, Beata Morawiec, Zbigniew Szemraj, Janusz Pawlowska, Zofia Chowdhury, Dipanjan Choi, Young Eun Kubiak, Robert Pakula, Lukasz Zawlik, Izabela TI Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE Breast cancer; microRNA; Pathologic response ID CELLS; LANDSCAPE AB Triple negative breast cancer (TNBC) has caught the attention of oncologists worldwide because of poor prognosis and paucity of targeted therapies. Gene pathways have been widely studied, but less is known about epigenetic factors such as microRNAs (miRNAs) and their role in tailoring an individual systemic and surgical approach for breast cancer patients. The aim of the study was to examine selected miRNAs in TNBC core biopsies sampled before preoperative chemotherapy and the subsequent pathologic response in mastectomy or breast conservation specimens. Prior to treatment, core needle biopsies were collected from 11 female patients with inoperable locally advanced TNBC or large resectable tumors suitable for down-staging. In all 11 TNBC core biopsies we analyzed 19 miRNAs per sample: 512, 190, 200, 346, 148, 449, 203, 577, 93, 126, 423, 129, 193, 182, 136, 135, 191, 122 and 222 (miRCURY LNA (TM) Universal RT microRNA polymerase chain reaction Custom Pick & Mixpanels). The Wilcoxon signed-rank test was used to compare related samples. Ingenuity pathway analysis was used to evaluate potential functional significance of differentially expressed miRNAs. Statistical analysis showed that 3 of 19 miRNAs differed in relation to pathologic response i.e. good versus poor. These differences failed to reach statistical significance, although a trend was observed (p = 0.06). Among these miRNAs, we identified-miR-200b-3p, miR-190a and miR-512-5p. In summary, our results indicate that higher miR-200b-3p, higher miR-190a and lower miR-512-5p expression levels in core biopsies sampled from TNBC patients may be associated with better pathologic response to chemotherapy and the increased feasibility of breast conserving surgery in these patients. Although these results were from a small cohort, they provide an important basis for larger, prospective, multicenter studies to investigate the potential role of miRNAs in neoadjuvant setting. C1 [Kolacinska, Agnieszka; Morawiec, Jan; Morawiec, Zbigniew] Copernicus Mem Hosp, Dept Surg Oncol, Ctr Canc, PL-93509 Lodz, Poland. [Morawiec, Jan] Med Univ Lodz, Dept Gen & Colorectal Surg, PL-90647 Lodz, Poland. [Fendler, Wojciech; Malachowska, Beata] Med Univ Lodz, Dept Pediat Oncol Hematol & Diabetol, PL-91738 Lodz, Poland. [Szemraj, Janusz] Med Univ Lodz, Dept Med Biochem, PL-92215 Lodz, Poland. [Pawlowska, Zofia] Med Univ Lodz, Cent Lab Corelab, PL-92215 Lodz, Poland. [Chowdhury, Dipanjan; Choi, Young Eun] Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Sch Med, Boston, MA 02215 USA. [Kubiak, Robert] Med Univ Lodz, Dept Pathol, PL-93513 Lodz, Poland. [Pakula, Lukasz] Copernicus Mem Hosp, Dept Anesthesiol, PL-93513 Lodz, Poland. [Zawlik, Izabela] Univ Rzeszow, Inst Nursing & Hlth Sci, Dept Med Genet, Dept Med, PL-35959 Rzeszow, Poland. RP Kolacinska, A (reprint author), Copernicus Mem Hosp, Dept Surg Oncol, Ctr Canc, Paderewskiego 4, PL-93509 Lodz, Poland. EM info@drkolacinska.pl RI Fendler, Wojciech/S-9592-2016 OI Fendler, Wojciech/0000-0002-5083-9168 FU Ministry of Science and Higher Education, Poland [2011/01/B/NZ4/03345] FX This study was supported by the grant of the Ministry of Science and Higher Education, Poland, 2011/01/B/NZ4/03345. NR 18 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD MAY PY 2014 VL 41 IS 5 BP 2851 EP 2857 DI 10.1007/s11033-014-3140-7 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG9JC UT WOS:000335734400017 PM 24469723 ER PT J AU Fontebasso, AM Papillon-Cavanagh, S Schwartzentruber, J Nikbakht, H Gerges, N Fisett, PO Bechet, D Faury, D De Jay, N Ramkissoon, LA Corcoran, A Jones, DTW Sturm, D Johann, P Tomita, T Goldman, S Nagib, M Bendel, A Goumnerova, L Bowers, DC Leonard, JR Rubin, JB Alden, T Browd, S Geyer, JR Leary, S Jallo, G Cohen, K Gupta, N Prados, MD Carret, AS Ellezam, B Crevier, L Klekner, A Bognar, L Hauser, P Garami, M Myseros, J Dong, ZF Siege, PM Malkin, HL Ligon, AH Albrecht, S Pfister, SM Ligon, KL Majewski, J Jabado, N Kieran, MW AF Fontebasso, Adam M. Papillon-Cavanagh, Simon Schwartzentruber, Jeremy Nikbakht, Hamid Gerges, Noha Fisett, Pierre-Olivier Bechet, Denise Faury, Damien De Jay, Nicolas Ramkissoon, Lori A. Corcoran, Aoife Jones, David T. W. Sturm, Dominik Johann, Pascal Tomita, Tadanori Goldman, Stewart Nagib, Mahmoud Bendel, Anne Goumnerova, Liliana Bowers, Daniel C. Leonard, Jeffrey R. Rubin, Joshua B. Alden, Tord Browd, Samuel Geyer, J. Russell Leary, Sarah Jallo, George Cohen, Kenneth Gupta, Nalin Prados, Michael D. Carret, Anne-Sophie Ellezam, Benjamin Crevier, Louis Klekner, Almos Bognar, Laszlo Hauser, Peter Garami, Miklos Myseros, John Dong, Zhifeng Siege, Peter M. Malkin, Hay Ley Ligon, Azra H. Albrecht, Steffen Pfister, Stefan M. Ligon, Keith L. Majewski, Jacek Jabado, Nada Kieran, Mark W. TI Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma SO NATURE GENETICS LA English DT Article ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; INTRINSIC PONTINE GLIOMAS; BMP RECEPTOR; HISTONE H3.3; I RECEPTOR; GLIOBLASTOMA; GENES; MOUSE; ALK2; SUBGROUPS AB Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with histone H3.1 p.Lys27Met substitution, whereas FGFR1 mutations or fusions occur in thalamic tumors associated with histone H3.3 p.Lys27Met substitution. Hyperactivation of the bone morphogenetic protein (BMP)-ACVR1 developmental pathway in mHGAs harboring ACVR1 mutations led to increased levels of phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of BMP downstream early-response genes in tumor cells. Global DNA methylation profiles were significantly associated with the p.Lys27Met alteration, regardless of the mutant histone H3 variant and irrespective of tumor location, supporting the role of this substitution in driving the epigenetic phenotype. This work considerably expands the number of potential treatment targets and further justifies pretreatment biopsy in pediatric mHGA as a means to orient therapeutic efforts in this disease. C1 [Fontebasso, Adam M.; Jabado, Nada] McGill Univ, Montreal Childrens Hosp, Div Expt Med, Montreal, PQ H3H 1P3, Canada. [Fontebasso, Adam M.; Jabado, Nada] McGill Univ, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [Papillon-Cavanagh, Simon; Nikbakht, Hamid; Gerges, Noha; Bechet, Denise; Faury, Damien; De Jay, Nicolas; Majewski, Jacek; Jabado, Nada] McGill Univ, Dept Human Genet, Montreal, PQ H3H 1P3, Canada. [Schwartzentruber, Jeremy] Wellcome Trust Sanger Inst, Hinxton, England. [Fisett, Pierre-Olivier; Albrecht, Steffen] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pathol, Montreal, PQ H3H 1P3, Canada. [Faury, Damien] McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. [Ramkissoon, Lori A.; Corcoran, Aoife; Ligon, Azra H.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Jones, David T. W.; Sturm, Dominik; Johann, Pascal; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany. [Tomita, Tadanori; Alden, Tord] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Dept Neurol Surg, Chicago, IL 60611 USA. [Goldman, Stewart] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat Hematol Oncol, Chicago, IL 60611 USA. [Nagib, Mahmoud] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Bendel, Anne] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, Minneapolis, MN USA. [Goumnerova, Liliana] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Goumnerova, Liliana; Ligon, Azra H.; Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA USA. [Bowers, Daniel C.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Leonard, Jeffrey R.] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO USA. [Rubin, Joshua B.] Washington Univ, Sch Med, Dept Pediat Hematol Oncol, St Louis, MO USA. [Browd, Samuel] Seattle Childrens Hosp, Dept Neurosurg, Seattle, WA USA. [Geyer, J. Russell; Leary, Sarah] Seattle Childrens Hosp, Canc & Blood Disorders Ctr, Seattle, WA USA. [Jallo, George] Johns Hopkins Univ Hosp, Dept Neurol Surg, Baltimore, MD 21287 USA. [Cohen, Kenneth] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Pediat Hematol Oncol, Baltimore, MD USA. [Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Carret, Anne-Sophie] Univ Montreal, CHU St Justine, Dept Hematol Oncol, Montreal, PQ, Canada. [Ellezam, Benjamin] Univ Montreal, CHU St Justine, Dept Pathol, Montreal, PQ, Canada. [Crevier, Louis] Univ Montreal, CHU St Justine, Dept Neurosurg, Montreal, PQ, Canada. [Klekner, Almos; Bognar, Laszlo] Univ Debrecen, Med & Hlth Sci Ctr, Dept Neurosurg, Debrecen, Hungary. [Hauser, Peter; Garami, Miklos] Semmelweis Univ, Dept Pediat 2, H-1085 Budapest, Hungary. [Myseros, John] Childrens Natl Med Ctr, Dept Neurosurg, Washington, DC 20010 USA. [Dong, Zhifeng; Siege, Peter M.] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ, Canada. [Malkin, Hay Ley] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ligon, Azra H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Kieran, Mark W.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. RP Ligon, KL (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. EM keith_ligon@dfci.harvard.edu; jacek.majewski@mcgill.ca; nada.jabado@mcgill.ca; mark_kieran@dfci.harvard.edu RI Pfister, Stefan/F-6860-2013; OI Pfister, Stefan/0000-0002-5447-5322; Leary, Sarah/0000-0003-0225-6184; Schwartzentruber, Jeremy/0000-0002-6183-2092; Kieran, Mark/0000-0003-2184-7692; Sturm, Dominik/0000-0003-0250-1696 FU Genome Canada; McGill University; Montreal Children's Hospital Foundation; Hungarian Scientific Research Fund (OTKA) [T-04639]; National Research and Development Fund (NKFP) [1A/002/2004]; TAMOP [-4.2.2A-11/1/KONV-2012-0025]; NCI [P01CA142536]; Zach Carson DIPG Fund at Dana-Farber Cancer Institute (DFCI); Mikey Czech Foundation; Maria Foundation; CIHR; Cedars Cancer Institute; McGill Integrated Cancer Research Training Program; Genome Quebec; Institute for Cancer Research of the Canadian Institutes for Health Research (CIHR); Chercheur Clinicien Senior Award; Ellie Kavalieros Fund (DFCI); Caroline Fund (DFCI); Ryan Harvey DIPG Fund (DFCI); Stop&Shop Pediatric Brain Tumor Program (DFCI); Pediatric Brain Tumor Clinical and Research Fund (DFCI); CIHR Systems Biology Training Program at McGill University; T.D.Trust/Montreal Children's Hospital Foundation FX The authors would like to express their sincere gratitude toward all staff at the McGill University and Genome Quebec Innovation Centre for excellent technical expertise, library preparation and sequencing. The authors are very grateful to J.-J. Lebrun (McGill University) for primer sequences and materials for SMAD signaling studies. This work was performed within the context of the I-CHANGE (International Childhood Astrocytoma Integrated Genomics and Epigenomics) Consortium and was supported by funding from Genome Canada, Genome Quebec, the Institute for Cancer Research of the Canadian Institutes for Health Research (CIHR), McGill University and the Montreal Children's Hospital Foundation. This work was also supported by Hungarian Scientific Research Fund (OTKA) contract T-04639: National Research and Development Fund (NKFP) contract 1A/002/2004 (P.H.and M.G.) and TAMOP-4.2.2A-11/1/KONV-2012-0025 (A.K. and LB.). N.J.is a member of the Penny Cole laboratory and the recipient of a Chercheur Clinicien Senior Award. J.Majewski holds a Canada Research Chair (tier 2). L.G., K.L.L. and M.W.K. are supported by NCI P01CA142536. We acknowledge the support of the Zach Carson DIPG Fund at the Dana-Farber Cancer Institute (DFCI), the Ellie Kavalieros Fund (DFCI), the Mikey Czech Foundation, the Prayer From Maria Foundation, the Hope for Caroline Fund (DFCI), the Ryan Harvey DIPG Fund (DFCI), the Stop&Shop Pediatric Brain Tumor Program (DFCI) and the Pediatric Brain Tumor Clinical and Research Fund (DFCI). A.M.F.is supported by a studentship from CIHR, as well as by an award from the CIHR Systems Biology Training Program at McGill University. D.B. is supported by a studentship from the T.D. Trust/Montreal Children's Hospital Foundation, and N. Gerges is supported by a studentship from the Cedars Cancer Institute. N.D.J. is supported by an award from the McGill Integrated Cancer Research Training Program. NR 22 TC 87 Z9 89 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 2014 VL 46 IS 5 BP 462 EP 466 DI 10.1038/ng.2950 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA AG4XE UT WOS:000335422900012 PM 24705250 ER PT J AU McNally, R Eck, MJ AF McNally, Randall Eck, Michael J. TI JAK-cytokine receptor recognition, unboxed SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID SIGNAL-TRANSDUCTION; FERM DOMAIN; JANUS KINASES; I INTERFERONS; SH2 DOMAIN; ALPHA; ACTIVATION; BINDING AB The crystal structure of the FERM-SH2 region of Tyk2 in complex with the cytoplasmic tail of an interferon-a receptor provides a first view of specific JAK-receptor recognition and reveals a central role of the heretofore-marginalized JAK SH2 domain in recognizing the cytokine-receptor box2 motif. C1 [McNally, Randall; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [McNally, Randall; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP McNally, R (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu NR 20 TC 2 Z9 2 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2014 VL 21 IS 5 BP 431 EP 433 DI 10.1038/nsmb.2824 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AG9CW UT WOS:000335717300003 PM 24799036 ER PT J AU Verfaellie, M Lafleche, G Spiro, A Bousquet, K AF Verfaellie, Mieke Lafleche, Ginette Spiro, Avron, III Bousquet, Kathryn TI Neuropsychological Outcomes in OEF/OIF Veterans With Self-Report of Blast Exposure: Associations With Mental Health, but not mTBI SO NEUROPSYCHOLOGY LA English DT Article DE TBI; blast injuries; PTSD; depression; neuropsychological outcome ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MILD HEAD-INJURY; IRAQ-WAR; POSTCONCUSSIVE SYMPTOMS; PROCESSING SPEED; COMBAT VETERANS; PERFORMANCE; SOLDIERS; PTSD AB Objective: To examine neuropsychological outcomes in veterans of Operations Enduring and Iraqi Freedom (OEF/OIF) with self-reported histories of blast exposure and determine the contribution of deployment-related mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD) and depression to performance. The effect of number of blast exposures and distance from the blast was also assessed. Method: OEF/OIF veterans who reported exposure to blast underwent structured interviews and were assigned to no-TBI (n = 39), mTBI without loss of consciousness (LOC; n = 53), or mTBI with LOC (n = 35) groups. They were administered tests of executive function, memory, and motor function at least 6 months after the index event. Results: Neuropsychological outcomes did not differ as a function of mTBI group. Blast load and distance from the blast also did not affect neuropsychological performance. Both PTSD and depression symptoms were significantly associated with neuropsychological outcomes. Conclusions: A history of mTBI with or without LOC during deployment does not contribute to objective cognitive impairment in the chronic phase post injury. In contrast, PTSD and depression symptoms are associated with cognitive performance decrements. This finding is thought to reflect at least in part the impact of psychiatric distress on neuropsychological performance. C1 [Verfaellie, Mieke; Lafleche, Ginette; Bousquet, Kathryn] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Verfaellie, Mieke; Lafleche, Ginette; Spiro, Avron, III; Bousquet, Kathryn] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 South Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu FU Clinical Science Research and Development; Rehabilitation Research and Development Services of the Department of Veterans Affairs FX This research was supported by the Clinical Science Research and Development and the Rehabilitation Research and Development Services of the Department of Veterans Affairs. The authors have no conflict of interest affecting this article. NR 65 TC 19 Z9 19 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAY PY 2014 VL 28 IS 3 BP 337 EP 346 DI 10.1037/neu0000027 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA AG3QH UT WOS:000335334000002 PM 24245929 ER PT J AU Tarnoki, AD Tarnoki, DL Medda, E Cotichini, R Stazi, MA Fagnani, C Nistico, L Lucatelli, P Boatta, E Zini, C Fanelli, F Baracchini, C Meneghetti, G Schillaci, G Osztovits, J Jermendy, G Kiss, RG Preda, I Karlinger, K Lannert, A Metneki, J Molnar, AA Garami, Z Berczi, V Halasz, I Baffy, G AF Tarnoki, Adam D. Tarnoki, David L. Medda, Emanuela Cotichini, Rodolfo Stazi, Maria A. Fagnani, Corrado Nistico, Lorenza Lucatelli, Pierleone Boatta, Emanuele Zini, Chiara Fanelli, Fabrizio Baracchini, Claudio Meneghetti, Giorgio Schillaci, Giuseppe Osztovits, Janos Jermendy, Gyorgy Kiss, Robert G. Preda, Istvan Karlinger, Kinga Lannert, Agnes Metneki, Julia Molnar, Andrea A. Garami, Zsolt Berczi, Viktor Halasz, Ildiko Baffy, Gyorgy TI Bioimpedance analysis of body composition in an international twin cohort SO OBESITY RESEARCH & CLINICAL PRACTICE LA English DT Article DE Genetics; Body composition parameters; Bioelectrical impedance analysis; Twin study ID X-RAY ABSORPTIOMETRY; MASS INDEX; ENVIRONMENTAL-INFLUENCES; REARED APART; MIDDLE-AGE; OBESITY; HERITABILITY; GENETICS; OVERWEIGHT; ADIPOSITY AB Objective: Multiple twin studies have demonstrated the heritability of anthropometric and metabolic traits. However, assessment of body composition parameters by bioimpedance analysis (BIA) has not been routinely performed in this setting. Design: A cross-sectional study. Setting: Study subjects were recruited and assessed at twin festivals or at major university hospitals in Italy, Hungary, and the United States to estimate the influence of genetic and environmental components on body composition parameters in a large, wide age range, international twin cohort by using bioelectrical impedance analysis. Subjects: 380 adult twin pairs (230 monozygotic and 150 dizygotic pairs; male:female ratio, 68:32; age years 49.1 +/- 15.4; mean +/- standard deviation; age range 18-82) were included in the analysis. Results: Heritability was calculated for weight (82%; 95% confidence interval [CI]: 78-85), waist and hip circumferences (74%; 95%CI: 68-79), body fat percentage (74%; 95%CI: 69-79), fat-free mass (74%; 95%CI: 69-79) and body mass index (79%; 95%CI: 74-83). The completely environmental model showed no impact of shared environmental effects on the variance, while unshared environmental effects were estimated as between 18% and 26%. Conclusions: BIA findings provide additional evidence to the heritability of anthropometric attributes related to obesity and indicate the practical value of this simple method in supporting efforts to prevent obesity-related adverse health events. (C) 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. C1 [Tarnoki, Adam D.; Tarnoki, David L.; Karlinger, Kinga; Berczi, Viktor] Semmelweis Univ, Dept Radiol & Oncotherapy, H-1082 Budapest, Hungary. [Medda, Emanuela; Cotichini, Rodolfo; Stazi, Maria A.; Fagnani, Corrado; Nistico, Lorenza] Ist Super Sanita, Genet Epidemiol Unit, I-00161 Rome, Italy. [Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio] Univ Roma La Sapienza, Dept Radiol Sci, Vasc & Intervent Radiol Unit, I-00162 Rome, Italy. [Baracchini, Claudio; Meneghetti, Giorgio] Univ Padua, Sch Med, Dept Neurosci, I-35128 Padua, Italy. [Schillaci, Giuseppe] Univ Perugia, Osped S Maria, Unite Med Interna, I-05100 Terni, Italy. [Osztovits, Janos; Jermendy, Gyorgy] Bajcsy Zsilinszky Hosp, Dept Internal Med 3, H-1106 Budapest, Hungary. [Kiss, Robert G.; Preda, Istvan; Molnar, Andrea A.] Hungarian Acad Sci, Res Grp Inflammat Biol & Immunogenom, H-1134 Budapest, Hungary. [Kiss, Robert G.; Preda, Istvan; Molnar, Andrea A.] Semmelweis Univ, H-1134 Budapest, Hungary. [Kiss, Robert G.; Preda, Istvan; Molnar, Andrea A.] Mil Hosp, State Hlth Ctr, Dept Cariol, H-1134 Budapest, Hungary. [Lannert, Agnes] Semmelweis Univ, Sch Pharm, H-1085 Budapest, Hungary. [Metneki, Julia] Natl Inst Hlth Dev, H-1096 Budapest, Hungary. [Garami, Zsolt] Methodist Hosp, DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Halasz, Ildiko; Baffy, Gyorgy] Harvard Univ, Sch Med, Dept Med, VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Tarnoki, AD (reprint author), Semmelweis Univ, Dept Radiol & Oncotherapy, 78-A Ulloi U, H-1082 Budapest, Hungary. EM tarnoki4@gmail.com RI Fagnani, Corrado/J-9069-2016; stazi, maria /K-4597-2016; Lucatelli, Pierleone/R-3188-2016 OI Fagnani, Corrado/0000-0001-5771-7772; Lucatelli, Pierleone/0000-0002-7448-1404 FU Balassi Institute - Hungarian Scholarship Board Office; Twins Days Festival committee; Istvan Luczek, MD FX Medexpert Ltd. has provided financial support for the development and maintenance of this study. Italian part of the research was supported by the Balassi Institute - Hungarian Scholarship Board Office. We would like to acknowledge the support of Twins Days Festival committee and Istvan Luczek, MD for the American part of the study. Studies were approved by local ethical committees (IRB committee names and project approval numbers: Semmelweis University Regional and Institutional Committee of Science and Research Ethics, 29/2009; Twins Days Festival Ethical Board, 1/2009; Ethical Committee of Istituto Superiore di Sanita). NR 36 TC 0 Z9 0 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1871-403X EI 1878-0318 J9 OBES RES CLIN PRACT JI Obes. Res. Clin. Pract. PD MAY-JUN PY 2014 VL 8 IS 3 BP E291 EP E297 DI 10.1016/j.orcp.2012.09.001 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AG8JB UT WOS:000335663500011 ER PT J AU Dizon, DS AF Dizon, Don S. TI Guilt and the Burden on Oncology Providers SO ONCOLOGIST LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM ddizon@partners.org NR 3 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2014 VL 19 IS 5 BP 441 EP 442 DI 10.1634/theoncologist.2014-0116 PG 2 WC Oncology SC Oncology GA AG5XS UT WOS:000335492700002 PM 24721814 ER PT J AU Krajewski, KM Franchetti, Y Nishino, M Fay, AP Ramaiya, N Van den Abbeele, AD Choueiri, TK AF Krajewski, Katherine M. Franchetti, Yoko Nishino, Mizuki Fay, Andre P. Ramaiya, Nikhil Van den Abbeele, Annick D. Choueiri, Toni K. TI 10% Tumor Diameter Shrinkage on the First Follow-Up Computed Tomography Predicts Clinical Outcome in Patients With Advanced Renal Cell Carcinoma Treated With Angiogenesis Inhibitors: A Follow-Up Validation Study SO ONCOLOGIST LA English DT Article DE Renal cell carcinoma; VEGF targeted therapy; RECIST 1.0; Choi; Tumor shrinkage ID CHOI RESPONSE CRITERIA; GUIDELINE VERSION 1.1; TARGETED THERAPY; SOLID TUMORS; SIZE; SUNITINIB; ATTENUATION; CT; SORAFENIB; SURVIVAL AB Background. Vascular endothelial growth factor (VEGF)targeted agents are standard therapies formetastatic renal cell carcinoma (mRCC), associated with variable tumor shrinkage. Response Evaluation Criteria in Solid Tumors (RECIST) is of limited utility in this setting, and other imaging changes are sought to reliably predict outcome early. We aim to validate 10% tumor shrinkage as the best early indicator of outcome. Methods. In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study, 66 mRCC patients with 165 lesions on clinical trials of VEGF-targeted agents underwent thoracic and abdominal computed tomography at baseline and at first follow-up after therapy. Measurements were performed according to RECIST and tumor shrinkage of >= 10% decrease in sum of the longest diameter (-10% SLD). Correlation with time-to-treatment failure (TTF) and overall survival (OS) were compared and stratified by response to the radiologic criteria. Receiver-operating characteristics (ROC) analysis yielded the optimal threshold change in SLD, defining patients with prolonged survival. Results. More than 210% SLD significantly differentiated responders from nonresponders (median TTF 8.4 vs. 4.1 months, p = .001), whereas partial response by RECIST did not (median TTF6.9vs.5.5months in responders vs. nonresponders, p = .34). 210% SLD was also significantly predictive of OS (median OS 35.1 vs. 15.0 months in responders vs. nonresponders, p = .003). ROC curve analysis yielded -9.3% in SLD as the optimal threshold for response/no response. Conclusion. Ten percent tumor shrinkage is validated as a reliable early predictor of outcome in mRCC patients receiving VEGF-targetedtherapies andmay providea practicalmeasureto guide therapeutic decisions. C1 [Krajewski, Katherine M.; Nishino, Mizuki; Ramaiya, Nikhil; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Krajewski, Katherine M.; Nishino, Mizuki; Ramaiya, Nikhil; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Franchetti, Yoko] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Franchetti, Yoko] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fay, Andre P.; Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. RP Krajewski, KM (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM kmkrajewski@partners.org FU NCI NIH HHS [K23 CA157631] NR 27 TC 16 Z9 16 U1 1 U2 3 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 MAY PY 2014 VL 19 IS 5 BP 507 EP 514 DI 10.1634/theoncologist.2013-0391 PG 8 WC Oncology SC Oncology GA AG5XS UT WOS:000335492700011 PM 24755461 ER PT J AU LeBaron, V Beck, SL Maurer, M Black, F Palat, G AF LeBaron, Virginia Beck, Susan L. Maurer, Martha Black, Fraser Palat, Gayatri TI An Ethnographic Study of Barriers to Cancer Pain Management and Opioid Availability in India SO ONCOLOGIST LA English DT Article DE Morphine; Palliative care; Cancer; World health; India; Opioids; Nursing; Pain management; Ethnography ID PALLIATIVE CARE; SOUTH-AFRICA; NURSES; RELIEF AB Background. The world's global cancer burden disproportionally affects lower income countries, where 80% of patients present with late-stage disease and have limited access to palliative care and effective pain-relieving medications, such as morphine. Consequently, millions die each year with unrelieved pain. Objective. The objective of this study was to examine barriers to opioid availability and cancer pain management in India, with an emphasis on the experiences of nurses, who are often the front-line providers of palliative care. Methods. Fifty-nine participants were recruited using a purposive, snowball sampling strategy. Ethnographic data collection included in-depth, semistructured interviews (n = 54), 4001 hours of participant observation, and review of documents over 9 months at a government cancer hospital in South India. Systematic qualitative analysis led to identification of key barriers that are exemplified by representative quotes. Results. Morphine is more available at this study site than in most of India, but access is limited to patients seen by the palliative care service, and significant gaps in supply still occur. Systems to measure and improve pain outcomes are largely absent. Key barriers related to pain management include the role of nursing, opioid misperceptions, bureaucratic hurdles, and sociocultural/infrastructure challenges. Implications. Interventions must streamline process details of morphine procurement, work within the existing sociocultural infrastructure to ensure opioids reach patients most in need, target unexpected audiences for symptom management education, and account for role expectations of health care providers. Conclusion. Macro-and micro-level policy and practice changes are needed to improve opioid availability and cancer pain management in India. C1 [LeBaron, Virginia] Univ Massachusetts, Dana Farber Canc Inst, Harvard Global Equ Initiat, Boston, MA 02125 USA. [Beck, Susan L.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Maurer, Martha] Univ Wisconsin, Carbone Canc Ctr, Pain & Policy Studies Grp, Madison, WI USA. [Black, Fraser] Victoria Hosp, Victoria, BC, Canada. RP LeBaron, V (reprint author), Phyllis F Cantor Ctr Res Nursing & Patient Care S, Dana Farber Canc Inst, 450 Brookline Ave,LG-517, Boston, MA 02215 USA. EM virginia_lebaron@dfci.harvard.edu NR 44 TC 9 Z9 9 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAY PY 2014 VL 19 IS 5 BP 515 EP 522 DI 10.1634/theoncologist.2013-0435 PG 8 WC Oncology SC Oncology GA AG5XS UT WOS:000335492700012 PM 24755460 ER PT J AU Schapira, L Blaszkowsky, LS Cashavelly, BJ Kim, CY Riley, JP Wold, MC Ryan, DP Penson, RT AF Schapira, Lidia Blaszkowsky, Lawrence S. Cashavelly, Barbara J. Kim, Christina Y. Riley, John P. Wold, Mali C. Ryan, David P. Penson, Richard T. TI Caring for One of Our Own SO ONCOLOGIST LA English DT Article DE Oncology; Support; Psychosocial; Cancer ID EMPATHY; VISITS AB Schwartz Center Rounds are monthly multidisciplinary meetings where caregivers reflect on important psychosocial issues that they, along with patients and their families, face and gain insightand support from fellow staff members, with the goal of advancing compassionate health care, supporting caregivers, and fostering the connection between a clinician and his or her patients. This Schwartz Round focused on boundaries and the particular privileges and pressures of caring for a member of the staff. The article explores the tension between professional courtesy and empathic engagement. Major transitions can include the intrinsic fear of abandonment. Being "connected" is an important aspect of the patient-caregiver relationship. Patient-centered care requires that we balance clinical acumen and medical technology with humanism throughout the different phases of a patient's experience with a life-threatening illness. C1 [Schapira, Lidia; Blaszkowsky, Lawrence S.; Cashavelly, Barbara J.; Kim, Christina Y.; Riley, John P.; Wold, Mali C.; Ryan, David P.; Penson, Richard T.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Yawkey Ctr Outpatient Care, 32 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 10 TC 4 Z9 4 U1 4 U2 6 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 MAY PY 2014 VL 19 IS 5 BP 545 EP 549 DI 10.1634/theoncologist.2014-0079 PG 5 WC Oncology SC Oncology GA AG5XS UT WOS:000335492700016 PM 24721818 ER PT J AU Sayegh, AI Washington, MC Raboin, SJ Aglan, AH Reeve, JR AF Sayegh, Ayman I. Washington, Martha C. Raboin, Shannon J. Aglan, Amnah H. Reeve, Joseph R., Jr. TI CCK-58 prolongs the intermeal interval, whereas CCK-8 reduces this interval: Not all forms of cholecystokinin have equal bioactivity SO PEPTIDES LA English DT Article DE Cholecystokinin; Satiation; Satiety; Satiety ratio; Intermeal interval ID PANCREATIC ACINAR-CELLS; DECREASES FOOD-INTAKE; FREE-FEEDING RATS; MEAL SIZE; BIOLOGICAL-ACTIVITY; ENZYME-SECRETION; SATIETY; PANCREOZYMIN; METABOLISM; RECEPTORS AB It has been accepted for decades that "all forms of cholecystokinin (CCK) have equal bioactivity," despite accumulating evidence to the contrary. To challenge this concept, we compared two feeding responses, meal size (MS, 10% sucrose) and intermeal interval (IMI), in response to CCK-58, which is the major endocrine form of CCK, and CCK-8, which is the most abundantly utilized form. Doses (0, 0.1, 0.5, 0.75, 1, 3 and 5 nmol/kg) were administered intraperitoneally over a 210-min test to Sprague Dawley rats that had been food-deprived overnight. We found that (1) all doses of CCK-58, except the lowest dose, and all doses of CCK-8, except the lowest two doses, reduced food intake more than vehicle did; (2) at two doses, 0.75 and 3 nmol/kg, CCK-58 increased the IMI, while CCK-8 failed to alter this feeding response; and (3) CCK-58, at all but the lowest two doses, increased the satiety ratio (IMI between first and second meals (min) divided by first MS (ml)) relative to vehicle, while CCK-8 did not affect this value. These findings demonstrate that the only circulating form of CCK in rats, CCK-58, prolongs the IMI more than CCK-8, the peptide generally utilized in feeding studies. Taken together, these results add to a growing list of functions where CCK-8 and CCK-58 express qualitatively different bioactivities. In conclusion, the hypothesis that "all forms of cholecystokinin (CCK) have equal bioactivity" is not supported. Published by Elsevier Inc. C1 [Sayegh, Ayman I.; Washington, Martha C.; Raboin, Shannon J.] Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. [Aglan, Amnah H.] Wayne State Univ, Sch Med, Detroit, MI USA. [Reeve, Joseph R., Jr.] Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Reeve, Joseph R., Jr.] Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Sayegh, AI (reprint author), Tuskegee Univ, Coll Vet Med, Dept Biomed Sci, Gastroenterol Lab, Tuskegee, AL 36088 USA. EM sayeghai@mytu.tuskegee.edu FU NIH [15C1DK094972-01A1]; Birmingham Racing Commission; [R01 DK083449] FX This study was supported by NIH 15C1DK094972-01A1 and the Birmingham Racing Commission (AIS) and R01 DK083449 (JRR, Jr.). NR 41 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD MAY PY 2014 VL 55 BP 120 EP 125 DI 10.1016/j.peptides.2014.02.014 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA AG6BR UT WOS:000335503900017 PM 24607725 ER PT J AU Wang, LX Mogami, S Karasawa, H Yamada, C Yakabi, S Yakabi, K Hattori, T Tache, Y AF Wang, Lixin Mogami, Sachiko Karasawa, Hiroshi Yamada, Chihiro Yakabi, Seiichi Yakabi, Koji Hattori, Tomohisa Tache, Yvette TI Preventive effect of rikkunshito on gastric motor function inhibited by L-dopa in rats SO PEPTIDES LA English DT Article DE Gastric motility; Ghrelin; L-dopa; Parkinson's disease; Rats; Rikkunshito ID TRADITIONAL JAPANESE MEDICINE; PARKINSONS-DISEASE; RESPONSE FLUCTUATIONS; GASTROINTESTINAL MOTILITY; GASTROESOPHAGEAL-REFLUX; HEALTHY-VOLUNTEERS; INDUCED ANOREXIA; HERBAL MEDICINE; PLASMA GHRELIN; ACYL GHRELIN AB We previously reported that ghrelin prevented L-dopa (LD)-induced inhibition of gastric emptying (GE) of a non-nutrient solution in rats. Parkinson's disease treatment involves the combined administration of L-dopa with the enzyme L-amino acid decarboxylase inhibitor, carbidopa (CD) to reduce peripheral formation of dopamine. We investigated the effect LD/CD given orogastrically (og) on GE of a non-nutrient or nutrient meal and whether og pretreatment with rikkunshito, a kampo medicine clinically used to treat gastroparesis, influenced LD/CD effect on GE and postprandial antral and duodenal motility in conscious rats. LD/CD (2012 mg kg) decreased significantly GE to 26.3 +/- 6.0% compared to 61.2 +/- 3.2% in og vehicle monitored 20-min after a non-nutrient meal and to 41.9 +/- 5.8% compared to 72.9 +/- 5.2% in og vehicle monitored 60 min after a nutrient meal. Rikkunshito (0.5 or 1.0 g kg(-1)) reduced the LD/CD (20/2 mg kg-1) inhibition of GE of non-nutrient meal (36.9 +/- 7.4% and 46.6 +/- 4.8% respectively vs. 12.1 +/- 7.4% in og vehicle plus LD/CD) while having no effect alone (56.6 +/- 8.5%). The ghrelin antagonist, [D-Lys(3)]-GHRP-6 (1 mg kg(-1)) injected intraperitoneally partially reversed rikkunshito preventive effect on LD/CD-inhibited GE. Rikkunshito (1.0 g kg(-1)) blocked LD/CD (20/2 mg kg(-1))-induced delayed GE of a nutrient meal and the reduction of postprandial antral motility. In 6-hydroxydopamine-induced Parkinson's disease rat model, rikkunshito (1.0 gkg(-1), og) also prevented LD/CD-inhibited gastric emptying of a nutrient meal and enhanced fasting plasma levels of acylated ghrelin. These data indicate that oral rikkunshito alleviates the delayed GE induced by LD/CD in naive and PD rat model in part through ghrelin-related mechanisms. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wang, Lixin; Karasawa, Hiroshi; Yakabi, Seiichi; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Ctr, Los Angeles, CA USA. [Wang, Lixin; Karasawa, Hiroshi; Yakabi, Seiichi; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Div Digest Dis, Ctr Neurobiol Stress, Los Angeles, CA 90024 USA. [Wang, Lixin; Karasawa, Hiroshi; Yakabi, Seiichi; Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Mogami, Sachiko; Yamada, Chihiro; Hattori, Tomohisa] Tsumura Res Labs, Ibaraki, Japan. [Yakabi, Koji] Saitama Med Univ, Saitama Med Ctr, Dept Gastroenterol & Hepatol, Saitama, Japan. RP Wang, LX (reprint author), 11301 Wilshire Blvd,Bldg 115, Los Angeles, CA 90073 USA. EM lixinw@ucla.edu RI Xu, Meiqu/C-5311-2016 FU Tsumura & Co. (Animal core, YT, LW) [NIHDDK-41303]; Fox Foundation Target Validation grant; Veterans Administration Research Career Scientist Award FX This work was supported by Tsumura & Co., NIHDDK-41303 (Animal core, YT, LW), Fox Foundation Target Validation grant (LW, YT), and Veterans Administration Research Career Scientist Award (YT). We are grateful to Mrs. Honghui Liang for excellent technical support and we thank Ms. Eugenia Hu for reviewing the manuscript. NR 66 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 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD MAY PY 2014 VL 55 BP 136 EP 144 DI 10.1016/j.peptides.2004.02.011 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA AG6BR UT WOS:000335503900020 PM 24631952 ER PT J AU Akil, O Hall-Glenn, F Chang, JL Li, A Chang, WH Lustig, LR Alliston, T Hsiao, EC AF Akil, Omar Hall-Glenn, Faith Chang, Jolie Li, Alfred Chang, Wenhan Lustig, Lawrence R. Alliston, Tamara Hsiao, Edward C. TI Disrupted Bone Remodeling Leads to Cochlear Overgrowth and Hearing Loss in a Mouse Model of Fibrous Dysplasia SO PLOS ONE LA English DT Article ID PROTEIN-COUPLED RECEPTOR; ENGINEERED G(S)-COUPLED RECEPTOR; MICE LACKING PROSAPOSIN; TEMPORAL BONE; OTIC CAPSULE; OSTEOBLAST EXPRESSION; G(I)-COUPLED RECEPTOR; INNER-EAR; OSTEOPROTEGERIN; OTOSCLEROSIS AB Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG) that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased G(s) G-protein coupled receptor (GPCR) signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3)(+)/Rs1(+) mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3)(+)/Rs1(+) mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3)(+)/Rs1(+) cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP) activity and receptor activator of nuclear factor kappa-B ligand (Rankl) mRNA expression. ColI(2.3)(+)/Rs1(+) cochleae also showed decreased expression of Sclerostin (Sost), an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3)(+)/Rs1(+) cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3)(+)/Rs1(+) cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13) and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the cochlea as well. Our findings suggest that factors regulating bone remodeling, including peri-lacunar remodeling by osteocytes, may be useful targets for treating the bony overgrowths and hearing changes of fibrous dysplasia and other bony pathologies. C1 [Akil, Omar; Chang, Jolie; Lustig, Lawrence R.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94117 USA. [Hall-Glenn, Faith; Alliston, Tamara] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. [Li, Alfred; Chang, Wenhan] San Francisco VA Med Ctr, Endocrine Unit, San Francisco, CA USA. [Li, Alfred; Chang, Wenhan] San Francisco VA Med Ctr, Bone Imaging Core, San Francisco, CA USA. [Hsiao, Edward C.] Univ Calif San Francisco, Dept Med, Div Endocrinol & Metab, San Francisco, CA USA. [Hsiao, Edward C.] Univ Calif San Francisco, Inst Human Genet, Dept Med, San Francisco, CA USA. RP Lustig, LR (reprint author), Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94117 USA. EM llustig@ohns.ucsf.edu; tamara.alliston@ucsf.edu; Edward.Hsiao@ucsf.edu OI Alliston, Tamara/0000-0001-9992-2897 FU Hearing Research Inc; NIH [R01 DE019284, K08 AR056299] FX This work was supported by Hearing Research Inc (TA, LL), NIH R01 DE019284 (TA), and NIH K08 AR056299 (ECH). The funders had no role in study design, data collection/analysis, decision to publish, or preparation of the manuscript. NR 54 TC 4 Z9 4 U1 0 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e94989 DI 10.1371/journal.pone.0094989 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600023 PM 24788917 ER PT J AU Kasper, L Seider, K Gerwien, F Allert, S Brunke, S Schwarzmuller, T Ames, L Zubiria-Barrera, C Mansour, MK Becken, U Barz, D Vyas, JM Reiling, N Haas, A Haynes, K Kuchler, K Hube, B AF Kasper, Lydia Seider, Katja Gerwien, Franziska Allert, Stefanie Brunke, Sascha Schwarzmueller, Tobias Ames, Lauren Zubiria-Barrera, Cristina Mansour, Michael K. Becken, Ulrike Barz, Dagmar Vyas, Jatin M. Reiling, Norbert Haas, Albert Haynes, Ken Kuchler, Karl Hube, Bernhard TI Identification of Candida glabrata Genes Involved in pH Modulation and Modification of the Phagosomal Environment in Macrophages SO PLOS ONE LA English DT Article ID KAPPA-B ACTIVATION; SACCHAROMYCES-CEREVISIAE; MYCOBACTERIUM-TUBERCULOSIS; HISTOPLASMA-CAPSULATUM; INVASIVE CANDIDIASIS; CRYPTOCOCCUS-NEOFORMANS; TORULOPSIS-GLABRATA; IMMUNE-RESPONSE; INNATE IMMUNE; HOST-DEFENSE AB Candida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine), differentiation (M1-/M2-type) or activation status (vitamin D-3 stimulation). We observed no differential activation of macrophage MAPK or NF kappa B signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NF kappa B signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore, protein mannosylation may play a key role in alterations of phagosomal properties caused by C. glabrata. C1 [Kasper, Lydia; Seider, Katja; Gerwien, Franziska; Allert, Stefanie; Brunke, Sascha; Zubiria-Barrera, Cristina; Hube, Bernhard] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Microbial Pathogen Mech, Jena, Germany. [Brunke, Sascha; Hube, Bernhard] Univ Hosp, Ctr Sepsis Control & Care, Integrated Res & Treatment Ctr, Jena, Germany. [Schwarzmueller, Tobias; Kuchler, Karl] Med Univ, Max F Perutz Labs, Dept Med Biochem, Vienna, Austria. [Ames, Lauren; Haynes, Ken] Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England. [Mansour, Michael K.; Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Becken, Ulrike] Labs Constant Burg, Paris, France. [Barz, Dagmar] Univ Hosp, Inst Transfus Med, Jena, Germany. [Reiling, Norbert] Res Ctr Borstel, Leibniz Ctr Med & Biosci, Div Microbial Interface Biol, Borstel, Germany. [Haas, Albert] Univ Bonn, Inst Cell Biol, Bonn, Germany. [Hube, Bernhard] Univ Jena, Jena, Germany. RP Hube, B (reprint author), Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Microbial Pathogen Mech, Jena, Germany. EM bernhard.hube@hki-jena.de RI Reiling, Norbert/D-6796-2013; Brunke, Sascha/G-1486-2012; Vyas, Jatin/Q-1627-2016; OI Reiling, Norbert/0000-0001-6673-4291; Brunke, Sascha/0000-0001-7740-4570; Vyas, Jatin/0000-0002-9985-9565; Hube, Bernhard/0000-0002-6028-0425 FU Deutsche Forschungsgemeinschaft [Hu 528/15-1, 16-1, Ha 1929/11-1, Re 1228/5-1, SPP1580]; National Institutes of Health [NIAID 1K08AI110655, 1R01AI079198, 1R01AI092084]; Wellcome Trust [097377/Z/11/Z]; BBSRC [BB/F005210/1]; [FWF-I 746-B11-DACH] FX This work was mainly supported by grants from the Deutsche Forschungsgemeinschaft to B. H. (Hu 528/15-1 and 16-1), A. H. (Ha 1929/11-1) and N.R. (Re 1228/5-1) within the priority program SPP1580 (www.spp1580.uni-bonn.de). Further, this work was in part supported by National Institutes of Health grants NIAID 1K08AI110655 (M. K. M.), 1R01AI079198 (J.M.V.), and 1R01AI092084 (J.M.V.). K. K. was funded by FWF-I 746-B11-DACH. Work in the Haynes lab was supported by grants from The Wellcome Trust (097377/Z/11/Z) and BBSRC (BB/F005210/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 14 Z9 14 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e96015 DI 10.1371/journal.pone.0096015 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600065 PM 24789333 ER PT J AU Stone, AEL Mitchell, A Brownell, J Miklin, DJ Golden-Mason, L Polyak, SJ Gale, MJ Rosen, HR AF Stone, Amy E. L. Mitchell, Angela Brownell, Jessica Miklin, Daniel J. Golden-Mason, Lucy Polyak, Stephen J. Gale, Michael J., Jr. Rosen, Hugo R. TI Hepatitis C Virus Core Protein Inhibits Interferon Production by a Human Plasmacytoid Dendritic Cell Line and Dysregulates Interferon Regulatory Factor-7 and Signal Transducer and Activator of Transcription (STAT) 1 Protein Expression SO PLOS ONE LA English DT Article ID CHRONIC HCV INFECTION; IFN-ALPHA PRODUCTION; RIG-I; ANTIVIRAL RESPONSE; RECOGNITION; THERAPY; IRF-7; GC1QR; INDUCTION; LIGAND AB Plasmacytoid Dendritic Cells (pDCs) represent a key immune cell population in the defense against viruses. pDCs detect viral pathogen associated molecular patterns (PAMPs) through pattern recognition receptors (PRR). PRR/PAMP interactions trigger signaling events that induce interferon (IFN) production to initiate local and systemic responses. pDCs produce Type I and Type III (IFNL) IFNs in response to HCV RNA. Extracellular HCV core protein (Core) is found in the circulation in chronic infection. This study defined how Core modulates PRR signaling in pDCs. Type I and III IFN expression and production following exposure to recombinant Core or beta-galactosiade was assessed in human GEN2.2 cells, a pDC cell line. Core suppressed type I and III IFN production in response to TLR agonists and the HCV PAMP agonist of RIG-I. Core suppression of IFN induction was linked with decreased IRF-7 protein levels and increased non-phosphorylated STAT1 protein. Circulating Core protein interferes with PRR signaling by pDCs to suppress IFN production. Strategies to define and target Core effects on pDCs may serve to enhance IFN production and antiviral actions against HCV. C1 [Stone, Amy E. L.; Mitchell, Angela; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Integrated Dept Immunol, Denver, CO 80202 USA. [Stone, Amy E. L.; Mitchell, Angela; Golden-Mason, Lucy; Rosen, Hugo R.] Natl Jewish Hlth, Denver, CO USA. [Stone, Amy E. L.; Mitchell, Angela; Miklin, Daniel J.; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Dept Med, Hepatitis C Ctr, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. [Brownell, Jessica; Polyak, Stephen J.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Polyak, Stephen J.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Gale, Michael J., Jr.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA. [Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Univ Colorado, Integrated Dept Immunol, Denver, CO 80202 USA. EM Hugo.Rosen@UCDENVER.edu OI Gale, Michael/0000-0002-6332-7436 FU NIH [U19 AI 1066328]; VA Merit Review grant; NIH/NCATS Colorado CTSI [TL1 TR000155] FX This work was supported by NIH U19 AI 1066328, a VA Merit Review grant and NIH/NCATS Colorado CTSI Grant Number TL1 TR000155. Contents are the authors' sole responsibility and do not necessarily represent official NIH views. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 9 Z9 9 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e95627 DI 10.1371/journal.pone.0095627 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600044 PM 24788809 ER PT J AU Maly, AG Steel, TL Fu, RW Lieberman, DA Becker, TM AF Maly, Annika G. Steel, Tessa L. Fu, Rongwei Lieberman, David A. Becker, Thomas M. TI Colorectal Cancer Screening Among American Indians in a Pacific Northwest Tribe: Cowlitz Tribal BRFSS Project, 2009-2010 SO PUBLIC HEALTH REPORTS LA English DT Article ID ALASKA-NATIVES; UNITED-STATES; COLON-CANCER; HEALTH; RISK; RECOMMENDATION; PREDICTORS; BARRIERS; NATION AB Objectives. Colorectal cancer (CRC) screening is low among American Indians (AIs). We describe the demographics, health status, prevalence of modifiable CRC risk factors, and use of CRC screening modalities in a Pacific Northwest AI tribe. Methods. We conducted a survey among Cowlitz tribal members using a Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. We analyzed demographic, health status, behavioral risk factor, and CRC screening variables. Using the Washington State 2010 BRFSS, we compared tribal members with non-Hispanic white (NHW) people. We used logistic regression to examine factors associated with CRC screening for tribal members. Results. A greater proportion of tribal members than NHW people reported living below the federal poverty level (12% vs. 7%, p=0.013). A greater proportion of tribal members than NHW people aged >= 50 years had poor self-reported health (27% vs. 16%, p=0.006) and were without health insurance (12% vs. 6%, p=0.004). A greater proportion of tribal members than NHW people had a fecal occult blood test within the past year (20% vs. 13%, p=0.006). Being 60-69 years of age (odds ratio [OR] = 2.6, 95% confidence interval [CI] 1.4, 4.9), >= 70 years of age (OR=2.2, 95% CI 1.1, 4.5), and having a personal health-care provider (OR=3.7, 95% CI 1.4, 9.6) were associated with increased screening adherence in tribal members. Conclusion. Data from the Cowlitz Tribal BRFSS demonstrate that members are receiving CRC screening in the same proportions as NHW people despite lower sociodemographic and health status indicators among members. Unique characteristics of the tribe likely contribute to this finding. C1 [Maly, Annika G.; Steel, Tessa L.; Fu, Rongwei; Becker, Thomas M.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Steel, Tessa L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Lieberman, David A.] Oregon Hlth & Sci Univ, Dept Gastroenterol, Portland, OR 97201 USA. [Becker, Thomas M.] Northwest Tribal Epidemiol Ctr, Northwest Area Indian Hlth Board, Portland, OR USA. RP Maly, AG (reprint author), Family Med Residence Idaho, 777 N Raymond St, Boise, ID 83704 USA. EM annika.maly@fmridaho.org FU Northwest Portland Area Indian Health Board (NPAIHB); Oregon Health and Science University (OHSU) FX The study was supported by the Northwest Portland Area Indian Health Board (NPAIHB) and Oregon Health and Science University (OHSU). The protocol was approved by Institutional Review Boards at NPAIHB and OHSU as well as by tribal leadership. Researchers were committed to following the principles of community-based participatory research and involved the Cowlitz Tribe Health and Human Services department at each step of the project. A community advisory board was developed to evaluate the results and provide feedback for this article. NR 39 TC 0 Z9 0 U1 0 U2 0 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 2014 VL 129 IS 3 BP 280 EP 288 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG4XH UT WOS:000335423200010 PM 24791026 ER PT J AU Maestre, JM Szyld, D del Moral, I Ortiz, G Rudolph, JW AF Maestre, J. M. Szyld, D. del Moral, I. Ortiz, G. Rudolph, J. W. TI The making of expert clinicians: Reflective practice SO REVISTA CLINICA ESPANOLA LA Spanish DT Article DE Debriefing; Reflective practice; Learning; Education; Clinical expert ID SIMULATION-BASED EDUCATION; DELIBERATE PRACTICE; PATIENT SAFETY; PERFORMANCE; ACQUISITION; DESIGN AB Debriefing is a rigorous reflection process which helps trainees recognize and resolve clinical and behavioral dilemmas raised by a clinical case. This approach emphasizes eliciting trainees'assumptions about the situation and their reasons for performing as they did (mental models). It analyses their impact on actions, to understand if it is necessary to maintain them or construct new ones that may lead to better performance in the future. It blends evidence and theory from education research, the social and cognitive sciences, and experience drawn from conducting and teaching debriefing to clinicians worldwide, on how to improve professional effectiveness through "reflective practice". (C) 2013 Elsevier Espana, S.L. All rights reserved. C1 [Maestre, J. M.; del Moral, I.] Hosp Valdecilla, Hosp Virtual Valdecilla, Serv Anestesiol & Reanimac, Santander, Spain. [Szyld, D.] NYU, Sch Med, New York Simulat Ctr Hlth Sci, Nueva York, NY USA. [Ortiz, G.] Hosp Santa Clara, Inst Simulac Med, Bogota, Colombia. [Rudolph, J. W.] Massachusetts Gen Hosp, Ctr Med Simulat, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Maestre, JM (reprint author), Hosp Valdecilla, Hosp Virtual Valdecilla, Serv Anestesiol & Reanimac, Santander, Spain. EM jmmaestre@hvvaldecilla.es OI Szyld, Demian/0000-0001-6609-7384 NR 30 TC 4 Z9 6 U1 1 U2 5 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0014-2565 EI 1578-1860 J9 REV CLIN ESP JI Rev. Clin. Esp. PD MAY PY 2014 VL 214 IS 4 BP 216 EP 220 DI 10.1016/j.rce.2013.12.001 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AG9BZ UT WOS:000335715000008 PM 24439667 ER PT J AU Zechmeister, I de Blasio, BF Garnett, G Neilson, AR Siebert, U AF Zechmeister, Ingrid de Blasio, Birgitte Freiesleben Garnett, Geoff Neilson, Aileen Rae Siebert, Uwe TI Cost-effectiveness analysis of human papillomavirus-vaccination programs to prevent cervical cancer in Austria (vol 27, pg 5133, 2009) SO VACCINE LA English DT Correction C1 [Zechmeister, Ingrid] Ludwig Boltzmann Inst Hlth Technol Assessment, A-1090 Vienna, Austria. [de Blasio, Birgitte Freiesleben] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Garnett, Geoff] Univ London Imperial Coll Sci Technol & Med, Inst Microparasite Epidemiol, London, England. [Neilson, Aileen Rae] Norwegian Knowledge Ctr Hlth Serv, Oslo, Norway. [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & HTA, Hall I T, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Zechmeister, I (reprint author), Ludwig Boltzmann Inst Hlth Technol Assessment, Garnisongasse 7-20, A-1090 Vienna, Austria. EM Ingrid.zechmeister@hta.lbg.ac.at RI Garnett, Geoffrey/A-9312-2008 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 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 1 PY 2014 VL 32 IS 21 BP 2520 EP 2520 DI 10.1016/j.vaccine.2014.03.006 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AG7RJ UT WOS:000335615200022 ER PT J AU Blumenthal, KG Saff, RR Banerji, A AF Blumenthal, Kimberly G. Saff, Rebecca R. Banerji, Aleena TI Evaluation and management of a patient with multiple drug allergies SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID INTRADERMAL SKIN-TEST; HYPERSENSITIVITY REACTIONS; IMMEDIATE HYPERSENSITIVITY; INTOLERANCE SYNDROME; PENICILLIN ALLERGY; CROSS-REACTIVITY; DIAGNOSIS; TESTS; CHALLENGE; CLARITHROMYCIN AB Multiple drug allergy syndrome (MDAS) is a clinical diagnosis made in patients with adverse reactions to two or more structurally unrelated drugs with an underlying immune-mediated mechanism causing the reaction. The evaluation of a patient with MDAS begins with a comprehensive drug allergy history and consideration of the underlying immune mechanism for each reaction. Skin testing is a useful diagnostic tool; however, the only validated immediate hypersensitivity skin testing is for penicillin where the antigenic determinants have been identified. Skin testing to most other drugs, although not validated, can be considered using a nonirritating concentration (NIC). In general, skin test positivity using an NIC suggests that the drug should be avoided, but a negative result does not rule out an IgE-mediated allergy. A test dose, also called a drug provocation test, graded oral challenge, or incremental challenge, should be performed when there is a low likelihood of an IgE-mediated mechanism for the reaction. In patients with a recent IgE-mediated hypersensitivity reaction or positive skin testing with no reasonable alternative treatment options, desensitization protocols can be used to allow the patient to safely receive a necessary drug. The evaluation of patients with MDAS is both challenging and time-consuming for the practicing allergist, who must systematically evaluate each reaction to help determine which drugs can be safely used again in the future. The molecular mechanisms and risk factors for this condition remain poorly understood, but research to further understand this condition is ongoing. C1 [Blumenthal, Kimberly G.; Saff, Rebecca R.; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Banerji, A (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. EM abanerji@partners.org NR 49 TC 4 Z9 4 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 EI 1539-6304 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAY-JUN PY 2014 VL 35 IS 3 BP 197 EP 203 DI 10.2500/aap.2014.35.3739 PG 7 WC Allergy SC Allergy GA AG6PD UT WOS:000335540000002 PM 24801461 ER PT J AU Vegh, EM Kandala, J Orencole, M Upadhyay, GA Sharma, A Miller, A Merkely, B Parks, KA Singh, JP AF Vegh, Eszter Maria Kandala, Jagdesh Orencole, Mary Upadhyay, Gaurav A. Sharma, Ajay Miller, Alexandra Merkely, Bela Parks, Kimberly A. Singh, Jagmeet P. TI Device-Measured Physical Activity Versus Six-Minute Walk Test as a Predictor of Reverse Remodeling and Outcome After Cardiac Resynchronization Therapy for Heart Failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TEST-PERFORMANCE; DIAGNOSTICS AB Implanted devices can provide objective assessment of physical activity over prolonged periods. The purpose of this study was to investigate the prognostic value of devicemeasured physical activity data compared with a six-minute walk test (6MWT) in predicting clinical response to cardiac resynchronization therapy (CRT). This was a singlecenter study in which patients who underwent CRT for standard indications were evaluated. Daily physical activity and 6MWT were evaluated postimplant at 1, 3, and 6 months. The primary end point was a composite of heart failure hospitalization, transplant, left ventricular (LV) assist device, and all-cause death at 3 years. Echocardiographk response, defined as a >= 10% improvement in LV ejection fraction (LVEF); at 6 months was the secondary end point. About 164 patients were included: average age was 67.3 +/- 12.9 years, 77% were men, baseline LVEF was 25% +/- 7%. Kaplan-Meier curves showed superior freedom from the composite end point in the highest tertile of both 6MWT and physical activity compared with the lowest tertile (41 vs 23 cases, respectively, p < 0.001) for 6MWT and for activity (22 vs 7 cases, respectively, p = 0.001). In an adjusted multivariate model, independent predictors of improved clinical outcome included 1-month physical activity (hazard ratio 0.546, 95% confidence interval [CI] 0.361 to 0.824, p = 0.004) and 6MWT (hazard ratio 0.581, 95% CI 0.425 to 0.795, p = 0.001). An additional hour of higher activity at 1 mouth translated to a 1.38 times (95% CI 1.075 to 1.753, p = 0.011) higher likelihood of improved echocardiographic response. In conclusion, device-based measures of physical-activity may be Useful in predicting echocardiographic reverse remodeling and long-term clinical outcome in patients receiving CRT. (C) 2014 Elsevier Inc. All rights reserved. C1 [Vegh, Eszter Maria; Kandala, Jagdesh; Orencole, Mary; Upadhyay, Gaurav A.; Sharma, Ajay; Miller, Alexandra; Parks, Kimberly A.; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Dept Cardiol, Boston, MA 02115 USA. [Vegh, Eszter Maria; Merkely, Bela] Semmelweis Univ, Dept Cardiol, Heart & Vasc Ctr, H-1085 Budapest, Hungary. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Dept Cardiol, Boston, MA 02115 USA. EM jsingh@partners.org NR 18 TC 5 Z9 5 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2014 VL 113 IS 9 BP 1523 EP 1528 DI 10.1016/j.amjcard.2014.01.430 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG4WS UT WOS:000335421700014 PM 24641966 ER PT J AU Sandora, TJ Graham, DA Conway, M Dodson, B Potter-Bynoe, G Margossian, SP AF Sandora, Thomas J. Graham, Dionne A. Conway, Margaret Dodson, Brenda Potter-Bynoe, Gail Margossian, Steven P. TI Impact of needleless connector change frequency on central line-associated bloodstream infection rate SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Pediatrics; Catheter-related infections ID INTENSIVE-CARE-UNIT; NOSOCOMIAL INFECTIONS; RISK-FACTORS; ATTRIBUTABLE MORTALITY; HOSPITAL COSTS; PREVENTION; PATIENT; DEVICE AB Background: Bloodstream infection is the most common pediatric health care-associated infection and is strongly associated with catheter use. These infections greatly increase the cost of hospital stay. Methods: To assess the association between needleless connector (NC) change frequency and central line-associated bloodstream infection (CLABSI) rate, we modeled monthly pediatric stem cell transplant (SCT) CLABSI rate in 3 periods: baseline period during which NC were changed every 96 hours regardless of infusate (period 1); trial period in which NC were changed every 24 hours with blood or lipid infusions (period 2); and a return to NC change every 96 hours regardless of infusate (period 3). Data on potential confounders were collected retrospectively. Autocorrelated segmented regression models were used to compare SCT CLABSI rates in each period, adjusting for potential confounders. CLABSI rates were also assessed for a nonequivalent control group (oncology unit) in which NC were changed every 24 hours with blood or lipid use in periods 2 and 3. Results: SCT CLABSI rates were 0.41, 3.56, and 0.03 per 1,000 central line-days in periods 1, 2, and 3, respectively. In multivariable analysis, the CLABSI rate was significantly higher in period 2 compared with both period 1 (P=.01) and period 3 (P=.003). In contrast, CLABSI rates on the oncology unit were not significantly different among periods. Conclusion: In pediatric SCT patients, changing needleless connectors every 24 hours when blood or lipids are infused is associated with increased CLABSI rates. National recommendations regarding NC change frequency should be clarified. Copyright (C) 2014 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Sandora, Thomas J.] Boston Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Sandora, Thomas J.] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Graham, Dionne A.] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Boston, MA 02115 USA. [Conway, Margaret] Boston Childrens Hosp, Dept Nursing, Boston, MA 02115 USA. [Dodson, Brenda] Boston Childrens Hosp, Dept Pharm, Boston, MA 02115 USA. [Potter-Bynoe, Gail] Boston Childrens Hosp, Boston, MA 02115 USA. [Margossian, Steven P.] Boston Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Margossian, Steven P.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Sandora, TJ (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM thomas.sandora@childrens.harvard.edu NR 26 TC 1 Z9 1 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAY PY 2014 VL 42 IS 5 BP 485 EP 489 DI 10.1016/j.ajic.2014.01.022 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AG5FE UT WOS:000335444000006 PM 24773786 ER PT J AU Alasil, T Wang, K Yu, F Field, MG Lee, H Baniasadi, N de Boer, JF Coleman, AL Chen, TC AF Alasil, Tarek Wang, Kaidi Yu, Fei Field, Matthew G. Lee, Hang Baniasadi, Neda de Boer, Johannes F. Coleman, Anne L. Chen, Teresa C. TI Correlation of Retinal Nerve Fiber Layer Thickness and Visual Fields in Glaucoma: A Broken Stick Model SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; SPECTRAL-DOMAIN OCT; LINEAR-MODEL; NORMAL EYES; STRATUS OCT; SENSITIVITY; REPRODUCIBILITY; NUMBER; DAMAGE; AGE AB PURPOSE: To determine the retinal nerve fiber layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss. DESIGN: Retrospective cross-sectional study. METHODS: Eighty-seven healthy and 108 glaucoma subjects (1 eye per subject) were recruited from an academic institution. All patients had VF examinations (Swedish Interactive Threshold Algorithm 24-2 test of the Humphrey Visual Field Analyzer 750i) and spectral-domain optical coherence tomography RNFL scans. Comparison of RNFL thickness values with VF threshold values showed a plateau of VF threshold values at high RNFL thickness values and then a sharp decrease at lower RNFL thickness values. A broken stick statistical analysis was used to estimate the tipping point at which RNFL thickness values are associated with VF defects. The slope for the association between structure and function was computed for data above and below the tipping point. RESULTS: The mean RNFL thickness value that was associated with initial VF loss was 89 mu m. The superior RNFL thickness value that was associated with initial corresponding inferior VF loss was 100 mu m. The inferior RNFL thickness value that was associated with initial corresponding superior VF loss was 73 mu m. The differences between all the slopes above and below the aforementioned tipping points were statistically significant (P < .001). CONCLUSIONS: In open-angle glaucoma, substantial RNFL thinning or structural loss appears to be necessary before functional visual field defects become detectable. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Field, Matthew G.; Baniasadi, Neda; Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wang, Kaidi; Chen, Teresa C.] Harvard Univ, Sch Med, Boston, MA USA. [Yu, Fei; Coleman, Anne L.] Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, Amsterdam, Netherlands. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM Teresa_Chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU Agency for Healthcare Research and Quality; Massachusetts Lions Eye Research Fund; American Glaucoma Society Mid-Career Award; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. Teresa C. Chen has received funding from the Agency for Healthcare Research and Quality, the Massachusetts Lions Eye Research Fund, and the American Glaucoma Society Mid-Career Award. Dr Chen has also received support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05) and financial contributions from Harvard University and its affiliated academic health care centers. Contributions of authors: design of the study (T.A., F,Y., H.L., T.C.C.); conduct of the study (T.A., J.F.D., T.C.C.); collection of data (T.A., K.W., M.G.F., N.B.), management (T.A., A.L.C., T.C.C.); analysis (T.A., F.Y., H.L., A.L.C., T.C.C.); interpretation of the data (T.A., F.Y., H.L., T.C.C.); preparation (T.A., T.C.C.), review (T.A., F.Y., H.L., T.C.C.), and approval of the manuscript (TA., K.W., F.Y., M.G.F., N.B., H.L., J.F.D., A.L.C., T.C.C.). NR 40 TC 11 Z9 12 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2014 VL 157 IS 5 BP 953 EP 959 DI 10.1016/j.ajo.2014.01.014 PG 7 WC Ophthalmology SC Ophthalmology GA AG1TU UT WOS:000335199900005 PM 24487047 ER PT J AU Keshavan, MS Vinogradov, S Rumsey, J Sherrill, J Wagner, A AF Keshavan, Matcheri S. Vinogradov, Sophia Rumsey, Judith Sherrill, Joel Wagner, Ann TI Cognitive Training in Mental Disorders: Update and Future Directions SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID DIRECT-CURRENT STIMULATION; REMEDIATION THERAPY CRT; PRIMARY MOTOR CORTEX; ADULT OWL MONKEYS; WORKING-MEMORY; ENHANCEMENT THERAPY; CORTICAL PLASTICITY; BIAS MODIFICATION; CONTROLLED-TRIAL; HAND REPRESENTATION AB Objective: This article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders. Method: The authors review the current state of the knowledge on cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future. Results: While much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including-attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitive training harnesses the inherent neuroplastic capacities of the brain, targeting neural system function across psychiatric disorders, thus improving the cognitive processes that play a, role in emotion regulation, clinical symptoms, and adaptive community functioning. Conclusions: Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in a-meliorating cognitive deficits. However, more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings. C1 [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NIMH, Clin Neurosci Res Branch, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. NIMH, Treatment & Prevent Intervent Res Branch, Div Serv & Intervent Res, Bethesda, MD 20892 USA. NIMH, Neurobehav Mechanisms Mental Disorders Branch, Div Dev Translat Res, Bethesda, MD 20892 USA. RP Keshavan, MS (reprint author), Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. EM mkeshava@bidmc.harvard.edu FU Sunovion; AmGen; Brain Plasticity Institute; EnVivo; Genentech; Hoffman La Roche; NIH [MH092440, MH060902, MH082818, MH068725, MH081051, MH081807]; Stanley Medical Research Institute; NIMH FX Dr. Keshavan has received grant funding from Sunovion. Dr. Vinogradov has received consulting fees from AmGen, Brain Plasticity Institute, EnVivo, Genentech, and Hoffman La Roche. The other authors report no financial relationships with commercial interests.; Dr. Keshavan has been supported by NIH grants MH092440 and MH060902. Dr. Vinogradov has been supported by NIH grants MH068725, MH082818, MH068725, MH081051, and MH081807 and the Stanley Medical Research Institute.; This research is based on a workshop sponsored by NIMH that was held on April 9 and 10, 2012. The workshop participants were Matcheri Keshavan, Harvard University (co-chair); Ann Wagner, NIMH (co-chair); Yair Bar-Haim, Tel Aviv University; Cameron Carter, University of California Davis; David Chambers, NIMH; Bruce Cuthbert, NIMH; Daniel Dickstein, Bradley Hospital/Brown University; Amy Dorin, FEGS Health and Human Services System, New York; Shaun Eack, University of Pittsburgh; Amit Etkin, Stanford University; Adam Gazzaley, University of California San Francisco; Russ Glasgow, National Cancer Institute; Adam Haim, NIMH; Jeffrey Halperin, Queens College; Courtenay Harding, The Coalition of Behavioral Health Agencies, New York; Robert Heinssen, NIMH; Thomas Insel, NIMH; Wendy Kates, SUNY Upstate Medical Center; Ellen Leibenluft, NIMH; Susan McGurk, Boston University; Alice Medalia, Columbia University; Sarah Morris, NIMH; Alvaro Pascual-Leone, Harvard Medical School; Daniel Pine, NIMH; Judith Rumsey, NIMH; Christopher Sarampote, NIMH; Suzy Scherf, Pennsylvania State University; Joel Sherrill, NIMH; David Sommers, NIMH; Leanne Tamm, Cincinnati Children's Hospital Medical Center; Carol Tamminga, University of Texas Southwestern Medical Center; Sophia Vinogradov, University of California San Francisco; Bruce Wexler, Yale University; Til Wykes, University of London Institute of Psychiatry. NR 99 TC 48 Z9 49 U1 8 U2 74 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2014 VL 171 IS 5 BP 510 EP 522 DI 10.1176/appi.ajp.2013.13081075 PG 13 WC Psychiatry SC Psychiatry GA AG0SI UT WOS:000335125500010 PM 24700194 ER PT J AU Tregellas, JR Smucny, J Harris, JG Olincy, A Maharajh, K Kronberg, E Eichman, LC Lyons, E Freedman, R AF Tregellas, Jason R. Smucny, Jason Harris, Josette G. Olincy, Ann Maharajh, Keeran Kronberg, Eugene Eichman, Lindsay C. Lyons, Emma Freedman, Robert TI Intrinsic Hippocampal Activity as a Biomarker for Cognition and Symptoms in Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; TEMPORAL-LOBE ABNORMALITIES; FUNCTIONAL CONNECTIVITY; NEGATIVE SYMPTOMS; HEMODYNAMIC-RESPONSE; BRAIN STRUCTURE; BATTERY MCCB; FMRI DATA; MEMORY; MRI AB Objective: Identification of biomarkers for cognitive dysfunction in schizophrenia is a priority for psychiatry research. Functional imaging studies suggest that intrinsic "resting state" hippocampal hyperactivity is a characteristic feature of schizophrenia. The relationships between this phenotype and symptoms of the illness, however, are largely unexplored. The authors examined resting hippocampal activity in schizophrenia patients and healthy comparison subjects and analyzed the relationship between intrinsic hippocampal activity and cognitive function in patients as measured by the MATRICS Consensus Cognitive Battery (MCCB). Method: Twenty-eight schizophrenia patients and 28 age-matched healthy comparison subjects underwent functional "resting state" 3-T MR scanning. Hippocampal activity was extracted by group independent component analysis. Correlation analyses were used to examine the relationship between hippocampal activity and MCCB composite and domain scores in patients, as well as between hippocampal activity and positive and negative symptoms. Results: Greater activity of the right hippocampus at rest was observed in patients relative to comparison subjects. In patients, a significant negative correlation was observed between right hippocampal activity and composite MCCB T-score. The correlation was driven by the MCCB domains of attention/vigilance, working memory, and visual learning. Hippocampal activity was positively correlated with negative symptoms. MCCB scores were inversely correlated with negative symptoms. Conclusions: These findings suggest that greater intrinsic hippocampal activity is a characteristic feature of schizophrenia that is broadly associated with cognitive dysfunction, and they support hippocampal activity as a candidate biomarker for therapeutic development. C1 [Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. Univ Colorado, Sch Med, Neurosci Program, Aurora, CO USA. Denver VA Med Ctr, Res Serv, Denver, CO USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Anschutz Med Campus, Aurora, CO 80045 USA. EM jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Smucny, Jason/0000-0001-5656-7987 FU NIMH Conte Center Grant [MH-086383]; VA Biomedical Laboratory and Clinical Science Research and Development Service; Brain and Behavior Research Foundation; Blowitz-Ridgeway Foundation FX Supported by NIMH Conte Center Grant MH-086383; the VA Biomedical Laboratory and Clinical Science Research and Development Service; the Brain and Behavior Research Foundation; and the Blowitz-Ridgeway Foundation. NR 57 TC 33 Z9 33 U1 4 U2 22 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2014 VL 171 IS 5 BP 549 EP 556 DI 10.1176/appi.ajp.2013.13070981 PG 8 WC Psychiatry SC Psychiatry GA AG0SI UT WOS:000335125500013 PM 24435071 ER PT J AU Kor, DJ Lingineni, RK Gajic, O Park, PK Blum, JM Hou, PC Hoth, JJ Anderson, HL Bajwa, EK Bartz, RR Adesanya, A Festic, E Gong, MN Carter, RE Talmor, DS AF Kor, Daryl J. Lingineni, Ravi K. Gajic, Ognjen Park, Pauline K. Blum, James M. Hou, Peter C. Hoth, J. Jason Anderson, Harry L., III Bajwa, Ednan K. Bartz, Raquel R. Adesanya, Adebola Festic, Emir Gong, Michelle N. Carter, Rickey E. Talmor, Daniel S. TI Predicting Risk of Postoperative Lung Injury in High-risk Surgical Patients A Multicenter Cohort Study SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; CLINICAL PREDICTORS; THORACIC-SURGERY; CARDIAC-SURGERY; SEPTIC SHOCK; TIDAL-VOLUME; ARDS; FAILURE; SEPSIS; CANCER AB Background: Acute respiratory distress syndrome (ARDS) remains a serious postoperative complication. Although ARDS prevention is a priority, the inability to identify patients at risk for ARDS remains a barrier to progress. The authors tested and refined the previously reported surgical lung injury prediction (SLIP) model in a multicenter cohort of at-risk surgical patients. Methods: This is a secondary analysis of a multicenter, prospective cohort investigation evaluating high-risk patients undergoing surgery. Preoperative ARDS risk factors and risk modifiers were evaluated for inclusion in a parsimonious risk-prediction model. Multiple imputation and domain analysis were used to facilitate development of a refined model, designated SLIP-2. Area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test were used to assess model performance. Results: Among 1,562 at-risk patients, ARDS developed in 117 (7.5%). Nine independent predictors of ARDS were identified: sepsis, high-risk aortic vascular surgery, high-risk cardiac surgery, emergency surgery, cirrhosis, admission location other than home, increased respiratory rate (20 to 29 and 30 breaths/min), Fio(2) greater than 35%, and Spo(2) less than 95%. The original SLIP score performed poorly in this heterogeneous cohort with baseline risk factors for ARDS (area under the receiver operating characteristic curve [95% CI], 0.56 [0.50 to 0.62]). In contrast, SLIP-2 score performed well (area under the receiver operating characteristic curve [95% CI], 0.84 [0.81 to 0.88]). Internal validation indicated similar discrimination, with an area under the receiver operating characteristic curve of 0.84. Conclusions: In this multicenter cohort of patients at risk for ARDS, the SLIP-2 score outperformed the original SLIP score. If validated in an independent sample, this tool may help identify surgical patients at high risk for ARDS. C1 [Kor, Daryl J.] Mayo Clin, Dept Anesthesiol, Rochester, MN 55905 USA. [Lingineni, Ravi K.; Carter, Rickey E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Gajic, Ognjen] Mayo Clin, Dept Med, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. [Park, Pauline K.] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. [Blum, James M.] Univ Michigan, Dept Anesthesiol, Sch Med, Ann Arbor, MI 48109 USA. [Anderson, Harry L., III] St Joseph Mercy Hosp, Dept Surg, Ann Arbor, MI 48104 USA. [Hou, Peter C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Hoth, J. Jason] Wake Forest Univ Hlth Sci, Dept Surg, Winston Salem, NC USA. [Bajwa, Ednan K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Bartz, Raquel R.] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. [Adesanya, Adebola] Univ Texas SW Med Ctr Dallas, Dept Anesthesiol, Dallas, TX 75390 USA. [Festic, Emir] Mayo Clin, Dept Crit Care, Jacksonville, FL 32224 USA. [Gong, Michelle N.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Talmor, Daniel S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Kor, DJ (reprint author), Mayo Clin, Dept Anesthesiol, 200 First St SW, Rochester, MN 55905 USA. EM kor.daryl@mayo.edu FU Foundation for Anesthesia Education and Research, Rochester, Minnesota; National Institutes of Health, Bethesda, Maryland [U01-HL108712-01, UL1 TR000135, KL2 TR000136]; Mayo Clinic Critical Care Research Committee, Rochester, Minnesota FX This study is supported by a Career Development Grant provided by the Foundation for Anesthesia Education and Research, Rochester, Minnesota; grant numbers U01-HL108712-01, UL1 TR000135, and KL2 TR000136, National Institutes of Health, Bethesda, Maryland; and the Mayo Clinic Critical Care Research Committee, Rochester, Minnesota. NR 57 TC 27 Z9 32 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2014 VL 120 IS 5 BP 1168 EP 1181 DI 10.1097/ALN.0000000000000216 PG 14 WC Anesthesiology SC Anesthesiology GA AG1KW UT WOS:000335175100017 PM 24755786 ER PT J AU Bateman, BT Hernandez-Diaz, S Rathmell, JP Seeger, JD Doherty, M Fischer, MA Huybrechts, KF AF Bateman, Brian T. Hernandez-Diaz, Sonia Rathmell, James P. Seeger, John D. Doherty, Michael Fischer, Michael A. Huybrechts, Krista F. TI Patterns of Opioid Utilization in Pregnancy in a Large Cohort of Commercial Insurance Beneficiaries in the United States SO ANESTHESIOLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; PRESCRIPTION DRUG-USE; POPULATION; EXPOSURES; TRENDS AB Background: There are few data regarding the utilization of opioids during pregnancy. The objective of this study was to define the prevalence and patterns of opioid use in a large cohort of pregnant women who were commercial insurance beneficiaries. Methods: Data for the study were derived from a deidentified research database of women from across the United States who had both medical and prescription benefits. By using diagnostic codes, the authors defined a cohort of 534,500 women with completed pregnancies who were enrolled in a commercial insurance plan from 6 months before pregnancy through delivery. Results: Overall, 76,742 women (14.4%) were dispensed an opioid at some point during pregnancy. There were 30,566 women (5.7%) dispensed an opioid during the first trimester, 30,434 women (5.7%) during the second trimester, and 34,906 women (6.5%) during the third trimester. Of these, 11,747 women (2.2%) were dispensed opioids three or more times during pregnancy. The most commonly dispensed opioids during pregnancy were hydrocodone (6.8%), codeine (6.1%), and oxycodone (2.0%). The prevalence of exposure at anytime during pregnancy decreased slightly during the study period from 14.9% for pregnancies that delivered in 2005 to 12.9% in 2011. The prevalence of exposure varied significantly by region and was lowest in the Northeast and highest in the South. Conclusions: This study demonstrates that opioids are very common exposures during pregnancy. Given the small and inconsistent body of literature on their safety in pregnancy, these findings suggest a need for research in this area. C1 [Bateman, Brian T.; Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Bateman, Brian T.; Seeger, John D.; Doherty, Michael; Fischer, Michael A.; Huybrechts, Krista F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM bbateman@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Bethesda, Maryland) [K08HD075831] FX Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Bethesda, Maryland) under Award Number K08HD075831 (to Dr. Bateman). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 27 TC 27 Z9 27 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2014 VL 120 IS 5 BP 1216 EP 1224 DI 10.1097/ALN.0000000000000172 PG 9 WC Anesthesiology SC Anesthesiology GA AG1KW UT WOS:000335175100021 PM 24525628 ER PT J AU Chen, KY Chen, L Mao, JR AF Chen, Kelly Yan Chen, Lucy Mao, Jianren TI Buprenorphine-Naloxone Therapy in Pain Management SO ANESTHESIOLOGY LA English DT Review ID OPIOID-INDUCED HYPERALGESIA; LOW-BACK-PAIN; PRIMARY-CARE; TRANSDERMAL BUPRENORPHINE; UNITED-STATES; DOUBLE-BLIND; CANCER PAIN; SUBLINGUAL BUPRENORPHINE; DEPENDENT PATIENTS; OPIATE ADDICTION AB Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone((R)); Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management. C1 [Chen, Kelly Yan] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. [Chen, Lucy; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. EM jmao@partners.org FU Foundation for Anesthesia Education and Research (Rochester, Minnesota); National Institutes of Health (Bethesda, Maryland) [DE18538, DE 22901, DA36564] FX Supported by Foundation for Anesthesia Education and Research (Rochester, Minnesota) Summer Research Grant (to Kelly Yan Chen) and National Institutes of Health (Bethesda, Maryland) R01 grants DE18538, DE 22901, DA36564 (to Jianren Mao and Lucy Chen). NR 73 TC 9 Z9 9 U1 7 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2014 VL 120 IS 5 BP 1262 EP 1274 DI 10.1097/ALN.0000000000000170 PG 13 WC Anesthesiology SC Anesthesiology GA AG1KW UT WOS:000335175100027 PM 24509068 ER PT J AU Leffert, LR Schwamm, LH AF Leffert, Lisa R. Schwamm, Lee H. TI Laterality of Motor Control and Breathing Share the Same Hemisphere: Considerations Regarding Neuroaxial Anesthesia in Cases with Intracranial Pathology In Reply SO ANESTHESIOLOGY LA English DT Letter ID ACUTE KIDNEY INJURY; NONCARDIAC SURGERY; PREDICTORS; TROPONIN C1 [Leffert, Lisa R.; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Leffert, LR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lleffert@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2014 VL 120 IS 5 BP 1278 EP 1278 DI 10.1097/ALN.0000000000000168 PG 1 WC Anesthesiology SC Anesthesiology GA AG1KW UT WOS:000335175100029 PM 24755789 ER PT J AU Ge, L Morrel, WG Ward, A Mishra, R Zhang, ZH Guccione, JM Grossi, EA Ratcliffe, MB AF Ge, Liang Morrel, William G. Ward, Alison Mishra, Rakesh Zhang, Zhihong Guccione, Julius M. Grossi, Eugene A. Ratcliffe, Mark B. TI Measurement of Mitral Leaflet and Annular Geometry and Stress After Repair of Posterior Leaflet Prolapse: Virtual Repair Using a Patient-Specific Finite Element Simulation SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVE REPAIR; LEFT-VENTRICLE; REGURGITATION; ANNULOPLASTY; DISEASE; DURABILITY; SOCIETY; MODEL; SHAPE AB Background. Recurrent mitral regurgitation after mitral valve (MV) repair for degenerative disease occurs at a rate of 2.6% per year and reoperation rate progressively reaches 20% at 19.5 years. We believe that MV repair durability is related to initial postoperative leaflet and annular geometry with subsequent leaflet remodeling due to stress. We tested the hypothesis that MV leaflet and annular stress is increased after MV repair. Methods. Magnetic resonance imaging was performed before and intraoperative three-dimensional (3D) transesophageal echocardiography was performed before and after repair of posterior leaflet prolapse in a single patient. The repair consisted of triangular resection and annuloplasty band placement. Images of the heart were manually co-registered. The left ventricle and MV were contoured, surfaced, and a 3D finite element (FE) model was created. Elements of the posterior leaflet region were removed to model leaflet resection and virtual sutures were used to repair the leaflet defect and attach the annuloplasty ring. Results. The principal findings of the current study are the following: (1) FE simulation of MV repair is able to accurately predict changes in MV geometry including changes in annular dimensions and leaflet coaptation; (2) average posterior leaflet stress is increased; and (3) average anterior leaflet and annular stress are reduced after triangular resection and mitral annuloplasty. Conclusions. We successfully conducted virtual mitral valve prolapse repair using FE modeling methods. Future studies will examine the effects of leaflet resection type as well as annuloplasty ring size and shape. (C) 2014 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, Dept Bioengn, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA USA. New York Sch Med, Dept Cardiothorac Surg, New York, NY USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Div Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@va.gov OI GROSSI, eugene/0000-0002-2066-7035 FU NIH [R01-HL-084431, 077921, 86400] FX This study was supported by NIH grants R01-HL-084431, 077921 and 86400. NR 25 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2014 VL 97 IS 5 BP 1496 EP 1503 DI 10.1016/j.athoracsur.2013.12.036 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AG5HX UT WOS:000335451200014 PM 24630767 ER PT J AU Shahian, DM He, X Jacobs, JP Rankin, JS Welke, KF Edwards, FH Filardo, G Fazzalari, FL Furnary, A Kurlansky, PA Brennan, JM Badhwar, V O'Brien, SM AF Shahian, David M. He, Xia Jacobs, Jeffrey P. Rankin, J. Scott Welke, Karl F. Edwards, Fred H. Filardo, Giovanni Fazzalari, Frank L. Furnary, Anthony Kurlansky, Paul A. Brennan, J. Matthew Badhwar, Vinay O'Brien, Sean M. TI The STS AVR plus CABG Composite Score: A Report of the STS Quality Measurement Task Force SO ANNALS OF THORACIC SURGERY LA English DT Article ID INTERNAL MAMMARY ARTERY; AORTIC-VALVE-REPLACEMENT; ADULT CARDIAC-SURGERY; BYPASS-SURGERY; SAPHENOUS-VEIN; CORONARY; GRAFTS; FLOW; OPERATIONS; MORTALITY AB Background. The Society of Thoracic Surgeons (STS) is developing a portfolio of composite performance measures for the most commonly performed adult cardiac procedures. This manuscript describes the third composite measure in this series, aortic valve replacement (AVR) combined with coronary artery bypass grafting surgery (CABG). Methods. We identified all patients in the STS Adult Cardiac Surgery Database who underwent AVR + CABG during recent 3-year (July 1, 2009, through June 30, 2012) and 5-year (July 1, 2007, through June 30, 2012) periods. Variables from the STS risk model for AVR + CABG were used to adjust morbidity and mortality outcomes. Evidence for internal mammary artery use in AVR + CABG was examined. We compared composite measures constructed using 3 or 5 years of outcomes with Bayesian credible intervals of 90%, 95%, or 98%. The final STS AVR + CABG composite performance measure is based on 3 years of data and 95% credible intervals. It includes risk-adjusted mortality and morbidity but not internal mammary artery use. Results. Median composite score is 91.0% (interquartile range, 89.5% to 92.2%). There were 2.6% (24 of 915) one-star (lower performing) and 6.5% (59 of 915) three-star (higher performing) programs. Morbidity and mortality decrease monotonically as star ratings increase. The percentage of three-star programs increased substantially among programs that performed more than 150 procedures over 3 years compared with those performing 25 to 50 procedures (32.8% versus 1.6 %). Measure reliability was 0.51. Conclusions. The STS has developed a composite performance measure for AVR + CABG based on 3-year data samples and 95% credible intervals. This composite measure identified 9.1% of STS participants as having higher or lower than expected performance. (C) 2014 by The Society of Thoracic Surgeons C1 [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Qual & Safety, Boston, MA USA. [He, Xia; Brennan, J. Matthew; O'Brien, Sean M.] Duke Clin Res Inst, Durham, NC USA. [Jacobs, Jeffrey P.] Johns Hopkins Univ, All Childrens Hosp, St Petersburg, FL USA. [Rankin, J. Scott] Vanderbilt Univ, Centennial Med Ctr, Nashville, TN 37235 USA. [Welke, Karl F.] Childrens Hosp Illinois, Peoria, IL USA. [Welke, Karl F.] Univ Illinois, Coll Med, Peoria, IL 61656 USA. [Edwards, Fred H.] Univ Florida, Coll Med, Jacksonville, FL USA. [Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [Fazzalari, Frank L.] Univ Michigan, Hlth Syst Cardiac Surg Dept, Crittenton Hosp, Rochester, MI USA. [Furnary, Anthony] Starr Wood Cardiac Grp, Portland, OR USA. [Kurlansky, Paul A.] Columbia HeartSource, New York, NY USA. [Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 28 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2014 VL 97 IS 5 BP 1604 EP 1609 DI 10.1016/j.athoracsur.2013.10.114 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AG5HX UT WOS:000335451200037 PM 24657032 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI The Sweet Approach Is Still Worthwhile in Modern Esophagectomy INVITED COMMENTARY SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 2 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2014 VL 97 IS 5 BP 1733 EP 1733 DI 10.1016/j.athoracsur.2014.02.001 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AG5HX UT WOS:000335451200063 PM 24792257 ER PT J AU Wright, C AF Wright, Cameron TI Thymoma Patients With Pleural Dissemination: Nationwide Retrospective Study of 136 Cases in Japan INVITED COMMENTARY SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID MULTIMODALITY THERAPY C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02144 USA. RP Wright, C (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St, Boston, MA 02144 USA. EM cdwright@partners.org NR 4 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2014 VL 97 IS 5 BP 1749 EP U346 DI 10.1016/j.athoracsur.2014.02.007 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AG5HX UT WOS:000335451200067 PM 24792259 ER PT J AU Roussos, P AF Roussos, Panos TI The Effect of Dopamine D1 Receptor on Cognitive Performance SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Roussos, Panos] James J Peters VAMC, Mt Sinai Sch Med, New York, NY USA. RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 9 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800011 ER PT J AU Siever, L AF Siever, Larry TI Dihydrexidine and Working Memory in the Schizophrenia Spectrum SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Dihydrexidine; working memory; D1 agonist; schizophrenia spectrum; schizotpal personality disorder C1 [Siever, Larry] James J Peters VAMC, Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 11 BP 4S EP 5S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800013 ER PT J AU Sachs, G AF Sachs, Gary TI Use of Quality Metrics as Eligibility Criteria to Improve Signal Detection SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Placebo response; Tandem Ratings; Computer Administered Rating; Quality Metrics; Methodology C1 [Sachs, Gary] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachs, Gary] Bracket, Wayne, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 94 BP 31S EP 31S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800096 ER PT J AU Jochems, J Lee, BG Blendy, JA Jarpe, M Mazitschek, R Van Duzer, JH Jones, S Berton, O AF Jochems, Jeanine Lee, Bridgin G. Blendy, Julie A. Jarpe, Matthew Mazitschek, Ralph Van Duzer, John H. Jones, Simon Berton, Olivier TI Antidepressant-like Properties of Novel HDAC6 Selective Inhibitors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE HDAC6; Social Defeat; HDAC inhibition; Depression; Antidepressant C1 [Jochems, Jeanine; Lee, Bridgin G.; Blendy, Julie A.; Berton, Olivier] Univ Penn, Philadelphia, PA 19104 USA. [Jarpe, Matthew; Van Duzer, John H.; Jones, Simon] Acetylon Pharmaceut, Res & Dev, Boston, MA USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 104 BP 34S EP 34S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800106 ER PT J AU Singh, J Fedgchin, M Daly, E De Boer, P Cooper, K Lim, P Pinter, C Murrough, J Sanacora, G Shelton, R Kurian, B Winokur, A Fava, M Manji, H Drevets, W Van Nueten, L AF Singh, Jaskaran Fedgchin, Maggie Daly, Ella De Boer, Peter Cooper, Kimberly Lim, Pilar Pinter, Christine Murrough, James Sanacora, Gerard Shelton, Richard Kurian, Benji Winokur, Andrew Fava, Maurizio Manji, Husseini Drevets, Wayne Van Nueten, Luc TI A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Dose Frequency Study of Intravenous Ketamine in Patients with Treatment-Resistant Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Ketamine; Treatment-Resistant Depression; Efficacy; Safety C1 [Singh, Jaskaran; Fedgchin, Maggie; Daly, Ella; Manji, Husseini; Drevets, Wayne] Janssen Res & Dev LLC, Neurosci, Titusville, NJ USA. [De Boer, Peter; Van Nueten, Luc] Janssen Res & Dev LLC, Neurosci, Beerse, Belgium. [Cooper, Kimberly] Janssen Res & Dev LLC, Clin Biostat, Spring House, PA USA. [Lim, Pilar] Janssen Res & Dev LLC, Clin Biostat, Titusville, NJ USA. [Pinter, Christine] Janssen Res & Dev LLC, GTM, Titusville, NJ USA. [Murrough, James] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Sanacora, Gerard] Yale Univ, Sch Med, New Haven, CT USA. [Shelton, Richard] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Kurian, Benji] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Winokur, Andrew] Inst Living, Hartford, CT USA. [Winokur, Andrew] Univ Connecticut, Farmington, CT USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. RI Murrough, James/J-7129-2013 OI Murrough, James/0000-0001-6286-1242 NR 0 TC 0 Z9 0 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 144 BP 44S EP 44S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800138 ER PT J AU Greenberg, T Chase, HW Almeida, J Stiffler, R Zevallos, CR Aslam, H Deckersbach, T Weyandt, S Cooper, C Kurian, BT McGrath, PJ Fava, M Weissman, MM Parsey, RV Trivedi, M Phillips, ML AF Greenberg, Tsafrir Chase, Henry W. Almeida, Jorge Stiffler, Richelle Zevallos, Carlos R. Aslam, Haris Deckersbach, Thilo Weyandt, Sarah Cooper, Crystal Kurian, Benji T. McGrath, Patrick J. Fava, Maurizio Weissman, Myrna M. Parsey, Ramin V. Trivedi, Madhukar Phillips, Mary L. TI Distinct Association Patterns in the Ventral Striatum between Reward Expectancy and Prediction Error Reactivity in Major Depressive Disorder versus Healthy Comparisons: Consistent Findings across Four Clinical Sites in the EMBARC Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE MDD; Reward; Prediction Error; Ventral Striatum; fMRI C1 [Greenberg, Tsafrir; Chase, Henry W.; Stiffler, Richelle; Zevallos, Carlos R.; Aslam, Haris; Phillips, Mary L.] Univ Pittsburgh, Pittsburgh, PA USA. [Almeida, Jorge] Brown Univ, Providence, RI 02912 USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weyandt, Sarah; Cooper, Crystal; Kurian, Benji T.; Trivedi, Madhukar] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [McGrath, Patrick J.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Weissman, Myrna M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Parsey, Ramin V.] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. RI Parsey, Ramin/J-8254-2014; Greenberg, Tsafrir /Q-7831-2016 NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 153 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800147 ER PT J AU Demanuele, C Bartsch, U Wamsley, EJ Shinn, AK Goff, DC Jones, MW Stickgold, R Manoach, DS AF Demanuele, Charmaine Bartsch, Ullrich Wamsley, Erin J. Shinn, Ann K. Goff, Donald C. Jones, Matthew W. Stickgold, Robert Manoach, Dara S. TI The Effects of Eszopiclone on Slow Wave Modulation of Sleep Spindles in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Sleep; Schizophrenia; Memory consolidation; Spindles; Slow waves C1 [Demanuele, Charmaine; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Demanuele, Charmaine; Goff, Donald C.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Bartsch, Ullrich; Jones, Matthew W.] Univ Bristol, Sch Physiol & Pharmacol, Bristol, Avon, England. [Wamsley, Erin J.; Stickgold, Robert] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Shinn, Ann K.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 187 BP 58S EP 58S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800181 ER PT J AU Walsh-Messinger, J Ramirez, PM Wong, P Antonius, D Aujero, N McMahon, K Opler, LA Malaspina, D AF Walsh-Messinger, Julie Ramirez, Paul Michael Wong, Philip Antonius, Daniel Aujero, Nicole McMahon, Kevin Opler, Lewis A. Malaspina, Dolores TI Impairment of Emotional Modulation of Attention and Memory in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Schizophrenia; Emotion Processing; Amygdala; Negative Symptoms C1 [Walsh-Messinger, Julie] Icahn Sch Med Mt Sinai, New York, NY USA. [Walsh-Messinger, Julie] James J Peters VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr MIRECC 3, Bronx, NY USA. [Ramirez, Paul Michael; Wong, Philip] Long Isl Univ, Brooklyn, NY USA. [Antonius, Daniel] SUNY Buffalo, Buffalo, NY 14260 USA. [Antonius, Daniel] Erie Cty Med Ctr & Labs, Forens Mental Hlth Serv, Buffalo, NY USA. [Antonius, Daniel; Aujero, Nicole; McMahon, Kevin] NYU, Sch Med, InSPIRES, New York, NY USA. [Opler, Lewis A.] Columbia Univ, New York, NY USA. [Malaspina, Dolores] NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 185 BP 58S EP 58S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800179 ER PT J AU Manoach, DS Demanuele, C Wamsley, EJ Montrose, D Miewald, J Kupfer, D Buysse, DJ Stickgold, R Keshavan, M AF Manoach, Dara S. Demanuele, Charmaine Wamsley, Erin J. Montrose, Debra Miewald, Jean Kupfer, David Buysse, Daniel J. Stickgold, Robert Keshavan, Matcheri TI Sleep Spindle Deficit in First Degree Relatives of Patients with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Schizophrenia; Sleep; Spindles; Memory; Genetic risk C1 [Manoach, Dara S.; Demanuele, Charmaine] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Manoach, Dara S.; Demanuele, Charmaine] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Wamsley, Erin J.; Stickgold, Robert; Keshavan, Matcheri] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Montrose, Debra; Miewald, Jean; Kupfer, David; Buysse, Daniel J.] Western Psychiat Inst & Clin, UPMC Hlth Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 188 BP 59S EP 59S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800182 ER PT J AU Wolthusen, R Boeke, EA Nasr, S Milad, MR Tootell, RBH Holt, DJ AF Wolthusen, Rick Boeke, Emily A. Nasr, Shahin Milad, Mohammed R. Tootell, Roger B. H. Holt, Daphne J. TI A Comparison of Autonomic and Explicit Measures of Fear Generalization SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Fear Generalization; Just Noticeable Difference; Autonomic and Explicit Measures; (Non-)Aversive Stimuli; Schizophrenia C1 [Wolthusen, Rick; Boeke, Emily A.; Nasr, Shahin; Milad, Mohammed R.; Tootell, Roger B. H.; Holt, Daphne J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wolthusen, Rick; Boeke, Emily A.; Nasr, Shahin; Milad, Mohammed R.; Tootell, Roger B. H.; Holt, Daphne J.] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Wolthusen, Rick] Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 197 BP 61S EP 62S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800191 ER PT J AU Gjeluci, K Leussis, M Meyer, F Eijsink, V Poelmans, G Martens, G Tracey, LP AF Gjeluci, Klaudio Leussis, Melanie Meyer, Francisca Eijsink, Vivian Poelmans, Geert Martens, Gerard Tracey, L. Petryshen TI Function of the Ankryin 3 Bipolar Disorder GWAS Gene in Response to Stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE ANK3; Bipolar; Stress; RNA-Seq; Disorders C1 [Gjeluci, Klaudio; Leussis, Melanie; Tracey, L. Petryshen] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Gjeluci, Klaudio; Leussis, Melanie; Tracey, L. Petryshen] Massachusetts Gen Hosp, Ctr Human Gene, Boston, MA 02114 USA. [Gjeluci, Klaudio] Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. [Gjeluci, Klaudio; Tracey, L. Petryshen] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Leussis, Melanie] Univ Cambridge Emmanuel Coll, Boston, MA USA. [Meyer, Francisca; Eijsink, Vivian; Poelmans, Geert; Martens, Gerard] Radboud Univ Nijmegen, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [Meyer, Francisca; Eijsink, Vivian; Poelmans, Geert; Martens, Gerard] Radboud Univ Nijmegen, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Meyer, Francisca; Eijsink, Vivian; Poelmans, Geert; Martens, Gerard] Radboud Univ Nijmegen, Med Ctr, Dept Mol Anim Physiol, NL-6525 ED Nijmegen, Netherlands. [Tracey, L. Petryshen] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RI Martens, Gerard/D-1925-2010; Poelmans, Geert/K-5997-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 219 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800213 ER PT J AU Blokland, GAM Petryshen, TL AF Blokland, Gabriella A. M. Petryshen, Tracey L. CA GENUS Consortium TI Genetic Association Studies of Cognitive and Neuroimaging Traits with Schizophrenia Risk Variants in the GENUS Consortium SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; genetics; cognition; neuroimaging; association C1 [Blokland, Gabriella A. M.; Petryshen, Tracey L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Blokland, Gabriella A. M.; Petryshen, Tracey L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Blokland, Gabriella A. M.; Petryshen, Tracey L.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 246 BP 77S EP 77S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800240 ER PT J AU Evans, KC McLaren, DG Song, TY Zimmerman, JP Dougherty, DD McNally, RJ Buckner, RL AF Evans, Karleyton C. McLaren, Donald G. Song, Tian-Yue Zimmerman, Jared P. Dougherty, Darin D. McNally, Richard J. Buckner, Randy L. TI Hypercapnia Evokes Differential Anxiety and Amygdala Blood Flow in Panic Disorder: Evidence for a Respiratory Subtype SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE panic; amygdala; carbon dioxide; fMRI; limbic C1 [Evans, Karleyton C.; McLaren, Donald G.; Song, Tian-Yue; Zimmerman, Jared P.; Dougherty, Darin D.; Buckner, Randy L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Evans, Karleyton C.; Dougherty, Darin D.] Harvard Univ, Sch Med, Boston, MA USA. [McNally, Richard J.; Buckner, Randy L.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 268 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800262 ER PT J AU Admon, R Holsen, LM Goldstein, JM Pizzagalli, DA AF Admon, Roee Holsen, Laura M. Goldstein, Jill M. Pizzagalli, Diego A. TI Reward Circuitry Hyperactivity during Stress in Remitted Individuals with Recurrent Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Stress; Reward; Depression; fMRi; Nucleus Accumbens C1 [Admon, Roee] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02178 USA. [Admon, Roee; Holsen, Laura M.; Goldstein, Jill M.; Pizzagalli, Diego A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Pizzagalli, Diego A.] McLean Hosp, McLean Imaging Ctr, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 285 BP 89S EP 90S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800279 ER PT J AU Blood, AJ Kuster, JK Lee, MJ Kim, B Lee, S Breiter, HC AF Blood, Anne J. Kuster, John K. Lee, Myung Joo Kim, Byoungwoo Lee, Sang Breiter, Hans C. TI fMRI Evidence Validating Structurally-Defined Depression Subtypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE depression; subtyping; expectancy; substantia nigra/ventral tegmental area; nucleus accumbens C1 [Blood, Anne J.; Kuster, John K.] Massachusetts Gen Hosp, Dept Psychiat, Lab Neuroimaging & Genet, Mood & Motor Control Lab, Charlestown, MA USA. [Lee, Myung Joo; Kim, Byoungwoo; Lee, Sang; Breiter, Hans C.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Warren Wright Adolescent Ctr, Chicago, IL 60611 USA. [Breiter, Hans C.] Harvard Univ, Sch Med, Dept Psychiat, Lab Neuroimaging & Genet, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 284 BP 89S EP 89S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800278 ER PT J AU Cobia, D Makris, N Lee, MJ Kim, B Lee, S Wang, L Blood, A Breiter, H AF Cobia, Derin Makris, Nikos Lee, Myung Joo Kim, Byoungwoo Lee, Sang Wang, Lei Blood, Anne Breiter, Hans TI Genetics-based Brain Mapping of Family with Benign Hereditary Chorea and Substance Abuse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Genetics; Chr14; Striatum; neuroimaging C1 [Cobia, Derin; Lee, Myung Joo; Kim, Byoungwoo; Lee, Sang; Wang, Lei; Breiter, Hans] Northwestern Univ, Chicago, IL 60611 USA. [Makris, Nikos; Blood, Anne] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 317 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800311 ER PT J AU Gilman, JM Kuster, JK Lee, S Lee, MJ Kim, B Makris, N van der Kouwe, A Blood, AJ Breiter, HC AF Gilman, Jodi M. Kuster, John K. Lee, Sang Lee, Myung Joo Kim, Byoungwoo Makris, Nikos van der Kouwe, Andre Blood, Anne J. Breiter, Hans C. TI Cannabis Use is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Cannabis; Nucleus Accumbens; Amygdala; Multimodal imaging; gray matter density C1 [Gilman, Jodi M.; Breiter, Hans C.] Harvard Univ, Sch Med, Dept Psychiat, Lab Neuroimaging & Genet, Charlestown, MA USA. [Kuster, John K.] Massachusetts Gen Hosp, Dept Psychiat, Mood & Motor Control Lab, Lab Neuroimaging & Genet, Charlestown, MA USA. [Lee, Sang; Lee, Myung Joo; Kim, Byoungwoo; Breiter, Hans C.] Northwestern Univ, Dept Psychiat & Behav Sci, Warren Wright Adolescent Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Makris, Nikos] Harvard Univ, Ctr Morphometr Anal, Sch Med, Dept Psychiat, Charlestown, MA USA. [van der Kouwe, Andre] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Blood, Anne J.] Harvard Univ, Sch Med, Dept Psychiat, Mood & Motor Control Lab,Lab Neuroimaging & Genet, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 324 BP 103S EP 103S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800318 ER PT J AU Hirano, Y Oribe, N Kanba, S Onitsuka, T Mesholam-Gately, R Seidman, LJ Shenton, ME Niznikiewicz, MA McCarley, RW Spencer, KM AF Hirano, Yoji Oribe, Naoya Kanba, Shigenobu Onitsuka, Toshiaki Mesholam-Gately, Raquelle Seidman, Larry J. Shenton, Martha E. Niznikiewicz, Margaret A. McCarley, Robert W. Spencer, Kevin M. TI Progressive gamma-Band Auditory Steady-State Responses Reduction in Clinical High Risk Subjects and First-Episode Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Auditory steady-state response; EEG; gamma oscillation; first-episode schizophrenia; clinical high risk C1 [Hirano, Yoji; Oribe, Naoya; Mesholam-Gately, Raquelle; Seidman, Larry J.; Shenton, Martha E.; Niznikiewicz, Margaret A.; McCarley, Robert W.; Spencer, Kevin M.] Harvard Univ, Sch Med, Boston, MA USA. [Hirano, Yoji; Oribe, Naoya; Spencer, Kevin M.] VA Boston Healthcare Syst, Neural Dynam Lab, Res Serv, Psychiat, Boston, MA USA. [Hirano, Yoji; Oribe, Naoya; Kanba, Shigenobu; Onitsuka, Toshiaki] Kyushu Univ, Grad Sch Med Sci, Fukuoka 812, Japan. [Mesholam-Gately, Raquelle; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Niznikiewicz, Margaret A.; McCarley, Robert W.] VA Boston Healthcare Syst, Lab Neurosci, Psychiat, Res Serv, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 325 BP 103S EP 103S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800319 ER PT J AU Lener, MS Wong, E Tang, CY Byne, W Goldstein, KE Blair, NJ Haznedar, MM New, AS Chemerinski, E Chu, KW Rimsky, LS Siever, LJ Koenigsberg, HW Hazlett, EA AF Lener, Marc S. Wong, Edmund Tang, Cheuk Y. Byne, William Goldstein, Kim E. Blair, Nicholas J. Haznedar, M. Mehmet New, Antonia S. Chemerinski, Eran Chu, King-Wai Rimsky, Liza S. Siever, Larry J. Koenigsberg, Harold W. Hazlett, Erin A. TI White Matter Abnormalities in Schizophrenia and Schizotypal Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE DTI; Schizophrenia; Schizotypal; White Matter; Structural C1 [Lener, Marc S.; Byne, William; Goldstein, Kim E.; Blair, Nicholas J.; Haznedar, M. Mehmet; New, Antonia S.; Rimsky, Liza S.; Siever, Larry J.; Koenigsberg, Harold W.; Hazlett, Erin A.] Icahn Sch Med Mt Sinai, New York, NY USA. [Wong, Edmund; Tang, Cheuk Y.] Icahn Sch Med Mt Sinai, Dept Radiol, Translat & Mol Imaging Inst, New York, NY USA. [Byne, William; Blair, Nicholas J.; New, Antonia S.; Chemerinski, Eran; Chu, King-Wai; Siever, Larry J.; Hazlett, Erin A.] Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Byne, William; Haznedar, M. Mehmet; New, Antonia S.; Chemerinski, Eran; Siever, Larry J.; Koenigsberg, Harold W.] James J Peters Vet Affairs Med Ctr, Outpatient Psychiat Dept, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 337 BP 107S EP 108S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800331 ER PT J AU Vuper, TC Xiao, JJ Agam, Y Robertson, EM Stickgold, R Manoach, DS AF Vuper, Tessa C. Xiao, Jingjing Agam, Yigal Robertson, Edwin M. Stickgold, Robert Manoach, Dara S. TI Resting State Connectivity of Primary Motor Cortex with the Hippocampus Predicts Subsequent Sleep-dependent Consolidation of Motor Sequence Learning SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE functional connectivity; hippocampus; resting state activity; memory consolidation; sleep C1 [Vuper, Tessa C.; Xiao, Jingjing; Agam, Yigal; Manoach, Dara S.] Massachusetts Gen Hosp, Charlestown, MA USA. [Robertson, Edwin M.; Stickgold, Robert] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 346 BP 111S EP 111S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800340 ER PT J AU Sher, L Grunebaum, MF Sullivan, GM Burke, AK Cooper, TB Mann, JJ Oquendo, MA AF Sher, Leo Grunebaum, Michael F. Sullivan, Gregory M. Burke, Ainsley K. Cooper, Thomas B. Mann, J. John Oquendo, Maria A. TI The Association of Testosterone Levels and Suicide Attempts in Women with Bipolar Disorder: A Prospective Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Testosterone; Bipolar; Suicide; Female; Prospective study C1 [Sher, Leo] James J Peters VA Med Ctr, New York, NY USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. 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Wolkowitz, Owen Epel, Elissa Mathalon, Daniel Vinogradov, Sophia TI Childhood Trauma, Cortisol Response to Psychosocial Stressors and Risk for Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Schizophrenia; Psychosis; Risk; Trauma; Stress C1 [Loewy, Rachel; Fulford, Daniel; Hua, Jessica; Schlosser, Danielle; Stuart, Barbara K.; Wolkowitz, Owen; Epel, Elissa; Mathalon, Daniel; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pearson, Rahel] Univ Texas Austin, Austin, TX 78712 USA. [Mathalon, Daniel; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 364 BP 116S EP 116S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800358 ER PT J AU Wang, WAD Ansari, A Osser, DN AF Wang, Wen Ao Dana Ansari, Arash Osser, David N. TI The Psychopharmacology Algorithm Project at the Harvard South Shore Program: 2014 Update on Bipolar Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Wang, Wen Ao Dana; Osser, David N.] Harvard Univ, VA Boston Hlth Care Syst, Dept Psychiat, Med Sch,Brockton Div, Brockton, MA 02401 USA. [Ansari, Arash] Harvard Univ, Brigham & Womens Faulkner Hosp, Dept Psychiat, Sch Med, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 404 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800398 ER PT J AU Perez-Rodriguez, MD AF Perez-Rodriguez, Maria De Las Mercedes TI Neuropeptides and BDNF and Emotion Dysregulation in Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE BDNF; amygdala; habituation; borderline personality disorder; emotion processing C1 [Perez-Rodriguez, Maria De Las Mercedes] Icahn Sch Med Mt Sinai, New York, NY USA. [Perez-Rodriguez, Maria De Las Mercedes] James J Peters VAMC, MIRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 537 BP 147S EP 147S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801038 ER PT J AU Perlis, RH Wang, J Haggarty, S AF Perlis, Roy H. Wang, Jennifer Haggarty, Steven TI A High-throughput Screening Approach for Lithium Responsiveness in Cellular Models of Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE iPS; cellular model; lithium; bipolar disorder; screening C1 [Perlis, Roy H.; Wang, Jennifer; Haggarty, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 594 BP 166S EP 166S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801095 ER PT J AU Kling, MA Appleby, DH Zhu, HJ Motsinger-Reif, AA Matson, W Arnold, SE Kaddurah-Daouk, R AF Kling, Mitchel A. Appleby, Dina H. Zhu, Hongjie Motsinger-Reif, Alison A. Matson, Wayne Arnold, Steven E. Kaddurah-Daouk, Rima CA Pharmacometabolomics Res Network TI Perturbations in Metabolic Pathways in Alzheimer-type Dementia and Mild Cognitive Impairment: Translational Implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Metabolomics; Alzheimer; networks; pathways; biomarkers C1 [Kling, Mitchel A.; Appleby, Dina H.; Arnold, Steven E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kling, Mitchel A.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Zhu, Hongjie; Kaddurah-Daouk, Rima] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA. [Motsinger-Reif, Alison A.] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Matson, Wayne] Bedford VA Med Ctr, Dept Syst Biochem, Bedford, MA USA. [Arnold, Steven E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 599 BP 168S EP 168S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801100 ER PT J AU Yao, JK AF Yao, Jeffrey K. TI Metabolic Perturbations of Monoamine Pathways in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Monoamine Pathways; Schizophrenia; First-episode psychosis; Neuroleptic-naive; Targeted metabolomics C1 [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 600 BP 168S EP 168S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801101 ER PT J AU Richardson, KA Buerger, E Ghorashi, S Whitford, TJ Mears, RP Buran, B Levenson, JM Gerber, D Spencer, KM Levin, ME AF Richardson, Kristen A. Buerger, Eric Ghorashi, Shahab Whitford, Thomas J. Mears, Ryan P. Buran, Brad Levenson, Jonathan M. Gerber, David Spencer, Kevin M. Levin, Margaret E. TI Identification of Neurophysiological (EEG) Signatures Associated with Novelty in Mouse and Man SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE EEG; Schizophrenia; Cognition; Biomarker; Novel Object Recognition Task C1 [Richardson, Kristen A.; Buerger, Eric; Buran, Brad; Levenson, Jonathan M.; Gerber, David; Levin, Margaret E.] Galenea, Translat Electrophysiol Grp, Wakefield, MA USA. [Ghorashi, Shahab; Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Res Serv,VA Boston Healthcare Syst, Boston, MA 02115 USA. [Whitford, Thomas J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 620 BP 175S EP 176S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801121 ER PT J AU Gatchel, JR Jordan-Arthur, B Lewandowski, KE McCabe, CF Harper, D Forester, B AF Gatchel, Jennifer R. Jordan-Arthur, Brittany Lewandowski, Kathryn E. McCabe, Cara F. Harper, David Forester, Brent TI Neuropsychological Function and Predictors of Cognitive Impairment in Geriatric Mood Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Major Depressive Disorder; Bipolar Disorder; Cognitive; Geriatric; Gender C1 [Gatchel, Jennifer R.] McLean Hosp, Massachusetts Gen Hosp, Boston, MA USA. 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TI Cognitive Contributions to Anxiety in Williams Syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Williams; Anxiety; Attention Bias; Dot Probe Task C1 [Dai, Yael; Clements, Caitlin; Weill, Sydney; Hoffnagle, Alison; Anderson, Erin; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [McGrath, Lauren M.] Amer Univ, Sch Educ Teaching & Hlth, Washington, DC 20016 USA. [Waxler, Jessica; Mullett, Jennifer; McDougle, Chris; Pober, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oates, Joyce] Amer Univ, Washington, DC 20016 USA. [MacRae, Rebecca] MIT, Boston, MA USA. [Dodd, Helen] Univ Reading, Sch Psychol & Clin Language Sci, Reading RG6 2AH, Berks, England. NR 0 TC 0 Z9 0 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 665 BP 190S EP 190S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801166 ER PT J AU Rimsky, L Reddan, M Brosch, T Koenigsberg, H Schiller, D AF Rimsky, Liza Reddan, Marianne Brosch, Tobias Koenigsberg, Harold Schiller, Daniela TI The Fundamental Attribution Error in Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE fundamental attribution error; borderline personality disorder; affective neuroscience; social decision-making C1 [Rimsky, Liza; Koenigsberg, Harold; Schiller, Daniela] Icahn Sch Med Mt Sinai, New York, NY USA. [Rimsky, Liza; Koenigsberg, Harold] James J Peters Bronx VA Med Ctr, Bronx, NY USA. [Reddan, Marianne] Univ Colorado Boulder, Boulder, CO USA. [Brosch, Tobias] Univ Geneva, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 698 BP 199S EP 200S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801198 ER PT J AU Soehner, AM Saletin, J Kaplan, KA Talbot, LS Hairston, IS Eidelman, P Gruber, J Walker, MP Harvey, AG AF Soehner, Adriane M. Saletin, Jared Kaplan, Katherine A. Talbot, Lisa S. Hairston, Ilana S. Eidelman, Polina Gruber, June Walker, Matthew P. Harvey, Allison G. TI You'll Feel Better in the Morning: Slow Wave Activity and Overnight Mood Regulation in Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Sleep; Mood C1 [Soehner, Adriane M.; Saletin, Jared; Walker, Matthew P.; Harvey, Allison G.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Kaplan, Katherine A.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Talbot, Lisa S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hairston, Ilana S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Eidelman, Polina] San Francisco Bay Area Ctr Cognit Therapy, Oakland, CA USA. [Gruber, June] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 697 BP 199S EP 199S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801197 ER EF