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Rosas S.E.,Philadelphia Veterans Administration Medical Center | Reese P.P.,University of Pennsylvania | Huan Y.,Thomas Jefferson University | Doria C.,Thomas Jefferson University | And 2 more authors.
American Journal of Nephrology | Year: 2012

Background: Low physical activity (PA) has been associated with higher rates of cardiovascular disease (CVD) and mortality in the general population. Despite the benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at elevated risk for CVD and mortality compared to individuals without kidney disease. Methods: A prospective cohort of 507 adult KTRs from three academic centers completed the Physical Activity Scale for the Elderly (PASE) at transplantation. PASE scores were divided into tertiles. Results: PA was lower with older age, history of CVD, smoking, and diabetes. During the median 8-year follow-up period, 128 individuals died, among whom 101 had a functioning allograft. In multivariable Cox regression for all-cause mortality, greater PA was strongly associated with better survival (HR: 0.52 for most active vs. inactive tertiles, 95% CI: 0.31-0.87, p = 0.01). Secondary analyses, in which (1) death with a functioning graft was the primary outcome, and (2) PASE scores were converted to the metabolic equivalent of task, revealed similar results. We did not find an association between change of PA after transplantation and mortality. Conclusions: PA at the time of kidney transplantation is a strong predictor of all-cause mortality and death with graft function. Evaluation of PA level among kidney transplant candidates may be a useful method to risk-stratify patients for survival after kidney transplantation. Kidney transplant candidates and recipients should also be encouraged to be physically active. Copyright © 2011 S. Karger AG, Basel.


Roalf D.R.,University of Pennsylvania | Gur R.E.,University of Pennsylvania | Ruparel K.,University of Pennsylvania | Calkins M.E.,University of Pennsylvania | And 6 more authors.
Neuropsychology | Year: 2014

Objective: The transition from childhood to adulthood is characterized by improved motor and cognitive performance in many domains. Developmental studies focus on average performance in single domains but ignore consistency of performance across domains. Within-individual variability (WIV) provides an index of that evenness and is a potential marker of development. Method: We gave a computerized battery of 14 neurocognitive tests to 9138 youths ages 8-21 from the Philadelphia Neurodevelopmental Cohort. Results: As expected, performance improved with age, with both accuracy and speed peaking in adulthood. WIV, however, showed a U-shaped course: highest in childhood, declining yearly into mid-adolescence, and increasing again into adulthood. Young females outperformed and were less variable than males, but by early adulthood male performance matched that of females despite being more variable. Conclusion: We conclude that WIV declines from childhood to adolescence as developmental lags are overcome, and then increases into adulthood reflecting the emergence of cognitive specializations related to skill-honing and brain maturation. © 2014 American Psychological Association.


Fisher M.B.,University of Pennsylvania | Fisher M.B.,Philadelphia Veterans Administration Medical Center | Mauck R.L.,University of Pennsylvania | Mauck R.L.,Philadelphia Veterans Administration Medical Center
Tissue Engineering - Part B: Reviews | Year: 2013

The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent "hot topics" and transformative publications within the field. Through this process, several key themes emerged: (1) tissue engineering: grafts and materials, (2) regenerative medicine: scaffolds and factors that control endogenous tissue formation, (3) clinical trials, and (4) novel cell sources: induced pluripotent stem cells. Within these focus areas, we summarize the highly impactful articles that emerged from our objective analysis and review additional recent publications to augment and expand upon these key themes. Finally, we discuss where the TERM field may be headed and how to monitor such a broad-based and ever-expanding community. © 2013 Mary Ann Liebert, Inc.


Adeseun G.A.,University of Pennsylvania | Rosas S.E.,University of Pennsylvania | Rosas S.E.,Philadelphia Veterans Administration Medical Center
Current Hypertension Reports | Year: 2010

Obstructive sleep apnea (OSA) is an important clinical problem in the chronic kidney disease (CKD) population. OSA is associated with hypoxemia and sleep fragmentation, which activates the sympathetic nervous system, the renin-angiotensin-aldosterone system, alters cardiovascular hemodynamics, and results in free radical generation. In turn, a variety of deleterious processes such as endothelial dysfunction, inflammation, platelet aggregation, atherosclerosis, and fibrosis are triggered, predisposing individuals to adverse cardiovascular events and likely renal damage. Independent of obesity, OSA is associated with glomerular hyperfiltration and may be an independent predictor of proteinuria, a risk factor for CKD progression. OSA is also associated with hypertension, another important risk factor for CKD progression, particularly proteinuric CKD. OSA may mediate renal damage via several mechanisms, and there is a need to better elucidate the impact of OSA on incident renal disease and CKD progression. © 2010 US Government.


Lei H.,University of Michigan | Nahum-Shani I.,University of Michigan | Lynch K.,University of Pennsylvania | Oslin D.,University of Pennsylvania | And 2 more authors.
Annual Review of Clinical Psychology | Year: 2012

Interventions often involve a sequence of decisions. For example, clinicians frequently adapt the intervention to an individual's outcomes. Altering the intensity and type of intervention over time is crucial for many reasons, such as to obtain improvement if the individual is not responding or to reduce costs and burden when intensive treatment is no longer necessary. Adaptive interventions utilize individual variables (severity, preferences) to adapt the intervention and then dynamically utilize individual outcomes (response to treatment, adherence) to readapt the intervention. The Sequential Multiple Assignment Randomized Trial (SMART) provides high-quality data that can be used to construct adaptive interventions. We review the SMART and highlight its advantages in constructing and revising adaptive interventions as compared to alternative experimental designs. Selected examples of SMART studies are described and compared. A data analysis method is provided and illustrated using data from the Extending Treatment Effectiveness of Naltrexone SMART study. © Copyright ©2012 by Annual Reviews. All rights reserved.


Plebani J.G.,University of Pennsylvania | Oslin D.W.,University of Pennsylvania | Oslin D.W.,Philadelphia Veterans Administration Medical Center | Lynch K.G.,University of Pennsylvania
American Journal on Addictions | Year: 2011

Prior clinical findings have indicated a potential lack of naltrexone efficacy among African Americans with alcohol dependence. However, no definitive conclusions have been drawn due to the relatively small numbers of African Americans in most alcohol treatment trials. The purpose of this study was to examine alcohol and naltrexone effects on healthy African-American individuals in a laboratory environment. Nonalcohol-dependent social drinking adults of African descent (n = 43) were recruited for participation. After consenting and completing the baseline assessment, they participated in four separate alcohol challenge sessions each separated by at least 10 days. During each of the sessions, subjects were administered alcohol or sham drinks, after pretreatment with either naltrexone (50 mg/day) or placebo in a double-blind fashion. The order of the four sessions was randomly assigned. During each session, breath alcohol levels and subjective responses were measured. Results indicate an alcohol effect among these subjects for subjective responses, but no naltrexone effect. Similar to the apparent lack of clinical efficacy findings, naltrexone does not appear to impact alcohol effects in African-American social drinkers. Future studies should investigate African-American populations with heavy drinking as well as alcohol-dependent subjects in order to strengthen the parallels to clinical findings. © American Academy of Addiction Psychiatry.


Fisher M.B.,University of Pennsylvania | Fisher M.B.,Philadelphia Veterans Administration Medical Center | Henning E.A.,University of Pennsylvania | Henning E.A.,Philadelphia Veterans Administration Medical Center | And 5 more authors.
Acta Biomaterialia | Year: 2013

The menisci are crescent-shaped fibrocartilaginous tissues whose structural organization consists of dense collagen bundles that are locally aligned but show a continuous change in macroscopic directionality. This circumferential patterning is necessary for load transmission across the knee joint and is a key design parameter for tissue engineered constructs. To address this issue we developed a novel electrospinning method to produce scaffolds composed of circumferentially aligned (CircAl) nanofibers, quantified their structure and mechanics, and compared them with traditional linearly aligned (LinAl) scaffolds. Fibers were locally oriented in CircAl scaffolds, but their orientation varied considerably as a function of position (P < 0.05). LinAl fibers did not change in orientation over a similar length scale (P > 0.05). Cell seeding of CircAl scaffolds resulted in a similar cellular directionality. Mechanical analysis of CircAl scaffolds revealed significant interactions between scaffold length and region (P < 0.05), with the tensile modulus near the edge of the scaffolds decreasing with increasing scaffold length. No such differences were detected in LinAl specimens (P > 0.05). Simulation of the fiber deposition process produced "theoretical" fiber populations that matched the fiber organization and mechanical properties observed experimentally. These novel scaffolds, with spatially varying local orientations and mechanics, will enable the formation of functional anatomic meniscus constructs. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Rubin M.F.,Massachussetts General Hospital | Rosas S.E.,Philadelphia Veterans Administration Medical Center | Rosas S.E.,University of Pennsylvania | Chirinos J.A.,Philadelphia Veterans Administration Medical Center | And 2 more authors.
American Journal of Kidney Diseases | Year: 2011

Although clinical cardiovascular outcomes, such as heart attack, stroke, and sudden cardiac death, have a dramatic onset, they result from prolonged exposure to an ever-growing array of risk factors. Several noninvasive procedures are available to assess the cumulative effect of these exposures with the goal of more precisely estimating a person's cardiovascular risk. These include ankle-brachial index, which provides an estimation of obstruction in major-vessel lumen caliber; carotid ultrasound, which evaluates carotid intima-media thickness and plaque, visibly quantifying atherosclerotic burden; aortic pulse wave velocity, which provides a measure of large-artery stiffness; and echocardiography, which measures left ventricular mass, providing a measure of subclinical hypertensive heart disease. In this narrative review, we discuss the role of each of these measures, with a particular emphasis on patients with chronic kidney disease. © 2011 National Kidney Foundation, Inc.


Workman A.D.,University of Pennsylvania | Cohen N.A.,University of Pennsylvania | Cohen N.A.,Philadelphia Veterans Administration Medical Center
American Journal of Rhinology and Allergy | Year: 2014

Background: Cilia in the human respiratory tract play a critical role in clearing mucus and debris from the airways. Their function can be affected by a number of drugs or other substances, many of which alter ciliary beat frequency (CBF). This has implications for diseases of the respiratory tract and nasal drug delivery. This article is a systematic review of the literature that examines 229 substances and their effect on CBF. Methods: MEDLINE was the primary database used for data collection. Eligibility criteria based on experimental design were established, and 152 studies were ultimately selected. Each individual trial for the substances tested was noted whenever possible, including concentration, time course, specific effect on CBF, and source of tissue. Results: There was a high degree of heterogeneity between the various experiments examined in this article. Substances and their general effects (increase, no effect, decrease) were grouped into six categories: antimicrobials and antivirals, pharmacologics, human biological products, organisms and toxins, drug excipients, and natural compounds/other manipulations. Conclusion: Organisms, toxins, and drug excipients tend to show a cilioinhibitory effect, whereas substances in all other categories had mixed effects. All studies examined were in vitro experiments, and application of the results in vivo is confounded by several factors. The data presented in this article should be useful in future respiratory research and examination of compounds for therapeutic and drug delivery purposes. Copyright © 2014, OceanSide Publications, Inc. U.S.A.


News Article | November 8, 2016
Site: globenewswire.com

PHILADELPHIA and OXFORD, United Kingdom, Nov. 08, 2016 (GLOBE NEWSWIRE) -- Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, today announced the appointment of Tal Zaks, M.D., Ph.D., to its Board of Directors as an independent Non-Executive Director effective from November 14, 2016. Dr. Zaks will also serve as a member of the Remuneration Committee. “We are very pleased that such a high caliber individual as Tal Zaks is joining our Board of Directors,” said Dr. Jonathan Knowles, Adaptimmune’s Chairman. “He brings extensive research and development and commercialization experience to augment our existing Board members’ expertise and support the advancement of our clinical programs.” “I am honored to join Adaptimmune,” commented Dr. Zaks. “I am impressed by the Company’s achievements, which include trials of its SPEAR T-cell therapies across multiple cancers allied to substantial research expertise and a prestigious network of partners. I look forward to working with the team as we translate our science and technology into effective therapies for cancer patients.” Tal Zaks, M.D., Ph.D. has served as the Chief Medical Officer of Moderna Therapeutics, Inc. since March 2015. He previously served as Senior Vice President and Head of Global Oncology at Sanofi Inc, where he was responsible for all aspects of oncology drug discovery, development and commercialization. Dr. Zaks began his industry career at GlaxoSmithKline in the genetics research group, where he built the oncology translational medicine team and led translational research on lapatinib as well as the in-licensing and clinical development of foretinib. In addition to his industry work, Dr. Zaks is an Adjunct Associate Professor of Medicine at the University of Pennsylvania and has served as a volunteer physician at the Philadelphia Veterans Administration Medical Center, treating patients with genitourinary cancers. Dr. Zaks received his M.D. and Ph.D. degrees from the Ben Gurion University in Israel and conducted post-doctoral research at the U.S. National Institutes of Health. He completed his clinical training in internal medicine at Temple University Hospital followed by a fellowship in medical oncology at the University of Pennsylvania. About Adaptimmune Adaptimmune is a clinical stage biopharmaceutical company focused on novel cancer immunotherapy products based on its SPEAR™ (Specific Peptide Enhanced Affinity Receptor) T-cell platform. Established in 2008, the Company aims to utilize the body’s own machinery - the T-cell - to target and destroy cancer cells by using engineered, increased affinity TCRs as a means of strengthening natural patient T-cell responses. Adaptimmune’s lead program is a SPEAR T-cell therapy targeting the NY-ESO cancer antigen. Its NY-ESO SPEAR T-cell therapy has demonstrated signs of efficacy and tolerability in Phase 1/2 trials in solid tumors and in hematologic cancer types, including synovial sarcoma and multiple myeloma. Adaptimmune has a strategic collaboration and licensing agreement with GlaxoSmithKline for the development and commercialization of the NY-ESO TCR program. In addition, Adaptimmune has a number of proprietary programs. These include SPEAR T-cell therapies targeting the MAGE-A10 and AFP cancer antigens, which both have open INDs, and a further SPEAR T-cell therapy targeting the MAGE-A4 cancer antigen that is in pre-clinical phase with IND acceptance targeted for 2017. The Company has identified over 30 intracellular target peptides preferentially expressed in cancer cells and is currently progressing 12 through unpartnered research programs. Adaptimmune has over 250 employees and is located in Oxfordshire, U.K. and Philadelphia, USA. For more information: http://www.adaptimmune.com Forward-Looking Statements This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 8, 2016, and our other SEC filings. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances.

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