A Feedback-Based Regularized Primal-Dual Gradient Method for Time-Varying Nonconvex Optimization

This paper considers time-varying nonconvex optimization problems, utilized to model optimal operational trajectories of systems governed by possibly nonlinear physical or logical models. Algorithms for tracking a Karush-Kuhn-Tucker point are synthesized, based on a regularized primal-dual gradient method. In particular, the paper proposes a feedback-based primal-dual gradient algorithm, where analytical models for system state or constraints are replaced with actual measurements. When cost and constraint functions are twice continuously differentiable, conditions for the proposed algorithms to have bounded tracking error are derived, and a discussion of their practical implications is provided. Illustrative numerical simulations are presented for an application in power systems

Quality of life of chronic stable angina patients 4 years after coronary angioplasty or coronary artery bypass surgery

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72244/1/j.1365-2796.2001.00782.x.pd

Alcohol, Tobacco, and Other Drugs: Future Directions for Screening and Intervention in the Emergency Department

This article is a product of a breakout session on injury prevention from the 2009 Academic Emergency Medicine consensus conference on “Public Health in the ED: Screening, Surveillance, and Intervention.” The emergency department (ED) is an important entry portal into the medical care system. Given the epidemiology of substance use among ED patients, the delivery of effective brief interventions (BIs) for alcohol, drug, and tobacco use in the ED has the potential to have a large public health impact. To date, the results of randomized controlled trials of interventional studies in the ED setting for substance use have been mixed in regard to alcohol and understudied in the area of tobacco and other drugs. As a result, there are more questions remaining than answered. The work group developed the following research recommendations that are essential for the field of screening and BI for alcohol, tobacco, and other drugs in the ED. 1) Screening—develop and validate brief and practical screening instruments for ED patients and determine the optimal method for the administration of screening instruments. 2) Key components and delivery methods for intervention—conduct research on the effectiveness of screening, brief intervention, and referral to treatment (SBIRT) in the ED on outcomes (e.g., consumption, associated risk behaviors, and medical psychosocial consequences) including minimum dose needed, key components, optimal delivery method, interventions focused on multiple risk behaviors and tailored based on assessment, and strategies for addressing polysubstance use. 3) Effectiveness among patient subgroups—conduct research to determine which patients are most likely to benefit from a BI for substance use, including research on moderators and mediators of intervention effectiveness, and examine special populations using culturally and developmentally appropriate interventions. 4) Referral strategies—a) promote prospective effectiveness trials to test best strategies to facilitate referrals and access from the ED to preventive services, community resources, and substance abuse and mental health treatment; b) examine impact of available community services; c) examine the role of stigma of referral and follow-up; and d) examine alternatives to specialized treatment referral. 5) Translation—conduct translational and cost-effectiveness research of proven efficacious interventions, with attention to fidelity, to move ED SBIRT from research to practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78664/1/j.1553-2712.2009.00552.x.pd

A Feedback-Based Regularized Primal-Dual Gradient Method for Time-Varying Nonconvex Optimization

This paper considers time-varying nonconvex optimization problems, utilized to model optimal operational trajectories of systems governed by possibly nonlinear physical or logical models. Algorithms for tracking a Karush-Kuhn-Tucker point are synthesized, based on a regularized primal-dual gradient method. In particular, the paper proposes a feedback-based primal-dual gradient algorithm, where analytical models for system state or constraints are replaced with actual measurements. When cost and constraint functions are twice continuously differentiable, conditions for the proposed algorithms to have bounded tracking error are derived, and a discussion of their practical implications is provided. Illustrative numerical simulations are presented for an application in power systems

Role of Peroxisome Proliferator-Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifunctional transcription factor with important regulatory roles in inflammation, cellular growth, differentiation, and apoptosis. PPARγ is expressed in a variety of immune cells as well as in numerous leukemias and lymphomas. Here, we review recent studies that provide new insights into the mechanisms by which PPARγ ligands influence hematological malignant cell growth, differentiation, and survival. Understanding the diverse properties of PPARγ ligands is crucial for the development of new therapeutic approaches for hematological malignancies

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Modulation of Cell Surface Protein Free Thiols: A Potential Novel Mechanism of Action of the Sesquiterpene Lactone Parthenolide

There has been much interest in targeting intracellular redox pathways as a therapeutic approach for cancer. Given recent data to suggest that the redox status of extracellular protein thiol groups (i.e. exofacial thiols) effects cell behavior, we hypothesized that redox active anti-cancer agents would modulate exofacial protein thiols.To test this hypothesis, we used the sesquiterpene lactone parthenolide, a known anti-cancer agent. Using flow cytometry, and western blotting to label free thiols with Alexa Fluor 633 C(5) maleimide dye and N-(biotinoyl)-N-(iodoacetyl) ethylendiamine (BIAM), respectively, we show that parthenolide decreases the level of free exofacial thiols on Granta mantle lymphoma cells. In addition, we used immuno-precipitation techniques to identify the central redox regulator thioredoxin, as one of the surface protein thiol targets modified by parthenolide. To examine the functional role of parthenolide induced surface protein thiol modification, we pretreated Granta cells with cell impermeable glutathione (GSH), prior to exposure to parthenolide, and showed that GSH pretreatment; (a) inhibited the interaction of parthenolide with exofacial thiols; (b) inhibited parthenolide mediated activation of JNK and inhibition of NFkappaB, two well established mechanisms of parthenolide activity and; (c) blocked the cytotoxic activity of parthenolide. That GSH had no effect on the parthenolide induced generation of intracellular reactive oxygen species supports the fact that GSH had no effect on intracellular redox. Together these data support the likelihood that GSH inhibits the effect of parthenolide on JNK, NFkappaB and cell death through its direct inhibition of parthenolide's modulation of exofacial thiols.Based on these data, we postulate that one component of parthenolide's anti-lymphoma activity derives from its ability to modify the redox state of critical exofacial thiols. Further, we propose that cancer cell exofacial thiols may be important and novel targets for therapy

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Over and Under-utilization of Cyclooxygenase-2 Selective Inhibitors by Primary Care Physicians and Specialists: The Tortoise and the Hare Revisited

To compare prescribing trends and appropriateness of use of traditional and cyclooxygenase-2 selective (COX-2) nonsteroidal anti-inflammatory drugs (NSAIDs) by primary care physicians (PCPs) and specialists. DESIGN : Retrospective cohort study. PATIENTS : One thousand five hundred and seventy-six adult patients continuously enrolled for at least 1 year with an independent practice association of a University-associated managed care plan who were started on a traditional NSAID or a COX-2 inhibitor from 1999 to 2002 and received at least 3 separate medication fills. MEASUREMENTS : Physician specialty was identified from office visits. Appropriateness of utilization was based on gastrointestinal risk characteristics. RESULTS : Primary care patients were younger and less likely to have comorbid conditions. Despite similar GI risk, COX-2 use among patients seen by PCPs was half that of patients seen by specialists (21% vs 44%, P <.001). While PCPs overused cyclooxygenase-2-specific inhibitors (COX-2s) less often than specialists (19% vs 41%, P <.001), they also tended to underuse COX-2s in patients who were at increased GI risk (46% vs 32%, P =.063). This represents a 3-fold and 8-fold difference in overuse versus underuse for PCPs and specialists, respectively. CONCLUSIONS : Using COX-2s as a model for physician adoption of new therapeutic agents, specialists were more likely to use these new medications for patients likely to benefit but were also significantly more likely to use them for patients without a clear indication. This study demonstrates the tension between appropriate adoption of innovative therapies for those individuals who would benefit from their use and those individuals who would receive no added clinical benefit but would incur added cost and be placed at increased risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75173/1/j.1525-1497.2006.00463.x.pd