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Introduction : A search for strategies to address saphenous vein graft (SVG) failure – the main factor limiting the long-term success of coronary bypass grafting – has led to trialing of external stenting technologies. Areas covered : The manuscript covers historical development and current status of external scaffolding for the treatment of SVG intimal hyperplasia. Comprehensive literature review and personal communication with VGS leadership, the developer of the VEST device, served as the sources. Expert opinion : If the external scaffolding concept proves to be successful in mitigating the intimal hyperplasia inherent to arterialized saphenous vein conduits, it could have a dramatic impact on the recurrence of anginal symptoms, the need for repeat revascularization, and the incidence of myocardial infarction following CABG surgery. These laudable sequelae could ultimately convey significant public health repercussions by reducing healthcare resource use and improving the long-term survival and quality of life of CABG recipients. [ABSTRACT FROM AUTHOR]

Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) is associated with worse survival after standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) chemoimmunotherapy compared to germinal center B-cell-like (GCB) subtype. Preliminary evidence suggests that benefits from novel agents may vary by subtype. Hypothesizing that treatment stratified by DLBCL subtype could be potentially cost-effective, we developed micro-simulation models to compare three first-line treatment strategies: (1) standard RCHOP for all patients (2) subtype testing followed by RCHOP for GCB and novel treatment for ABC DLBCL, and (3) novel treatment for all patients. Based on phase 2 evidence, we used lenalidomide + RCHOP as a surrogate novel treatment. The subtype-based approach showed a favorable incremental cost-effectiveness ratio of $15,015/quality-adjusted life year compared with RCHOP. Although our exploratory analyses demonstrated a wide range of conditions where subtype-based treatment remained cost-effective, data from phase 3 trials are needed to validate our models’ findings and draw definitive conclusions. [ABSTRACT FROM AUTHOR]

Introduction: Despite its FDA approval and incorporation into the National Comprehensive Cancer Network (NCCN) treatment guidelines, ramucirumab (RAM) is associated with a drug acquisition cost that is substantially higher than other approved options. Given its substantial cost, the presence of a viable alternative treatment option, and its minimal survival improvement, the usefulness of RAM in clinical practice has been called into question. Areas covered: In this paper, we outline the cost, benefits, and economic implications of RAM from a US perspective, as it is used in the treatment of mCRC. We also dissect its use in other tumor types and in other healthcare systems around the world, and briefly compare it with similar drugs targeting the vascular endothelial growth factor pathway. We used the search engine PubMed using the following as search terms: cost-effectiveness; ramucirumab; metastatic colon cancer; angiogenesis; and value-based medicine. Expert commentary: The use of ramucirumab in the treatment of mCRC serves as a microcosm of the worsening healthcare crisis within the US and the ongoing controversy regarding oncology drug costs, benefits, and value. Therefore, there must be a joint effort in moving towards value based pricing models. [ABSTRACT FROM AUTHOR]

We have previously described high rates of executive function impairment in clients referred by Adult Protective Services (APS) to geriatric psychiatry for decision-making capacity assessments. The purpose of this study was to determine the independent relationship between neuropsychological screening instruments, particularly instruments sensitive to executive function, and performance-based functional tasks in elder referrals. Our retrospective medical review (n = 75/157 referrals completed all neuropsychological and functional assessments) revealed that only the Executive Interview (EXIT25) contributed independent variance to money management performance (R2= 0.29, p < 0.001), telephone use ability (R2= 0.39, p < 0.001), and summed performance (R2= 0.45, p < 0.001). Executive instruments may specifically inform decision-making capacity assessments. [ABSTRACT FROM AUTHOR]

Context. The case fatality from acute poisoning with glyphosate-containing herbicides is approximately 7.7% from the available studies but these have major limitations. Large prospective studies of patients with self-poisoning from known formulations who present to primary or secondary hospitals are needed to better describe the outcome from acute poisoning with glyphosate-containing herbicides. Furthermore, the clinical utility of the glyphosate plasma concentration for predicting clinical outcomes and guiding treatment has not been determined. Objective. To describe the clinical outcomes, dose–response, and glyphosate kinetics following self-poisoning with glyphosate-containing herbicides. Methods. This prospective observational case series was conducted in two hospitals in Sri Lanka between 2002 and 2007. We included patients with a history of acute poisoning. Clinical observations were recorded until discharge or death. During a specified time period, we collected admission (n = 216, including five deaths) and serial (n = 26) blood samples in patients. Severity of poisoning was graded using simple clinical criteria. Results. Six hundred one patients were identified; the majority ingested a concentrated formulation (36%, w/v glyphosate). Twenty-seven percent were asymptomatic, 63.7% had minor poisoning, and 5.5% of patients had moderate to severe poisoning. There were 19 deaths (case fatality 3.2%) with a median time to death of 20 h. Gastrointestinal symptoms, respiratory distress, hypotension, altered level of consciousness, and oliguria were observed in fatal cases. Death was strongly associated with greater age, larger ingestions, and high plasma glyphosate concentrations on admission (>734 μg/mL). The apparent elimination half-life of glyphosate was 3.1 h (95% CI = 2.7–3.6 h). Conclusions. Despite treatment in rural hospitals with limited resources, the mortality was 3.2%, which is lower than that reported in previous case series. More research is required to define the mechanism of toxicity, better predict the small group at risk of death, and find effective treatments. [ABSTRACT FROM AUTHOR]

Stochastic coherent adaptive large eddy simulation (SCALES) is an extension of large eddy simulation that uses a wavelet filter-based dynamic grid adaptation strategy to solve for the most energetic coherent structures in a turbulent flow field, while modeling the effect of the less energetic ones. A localized dynamic subgrid scale model is needed to fully exploit the ability of the method to track coherent structures. In this paper, new local Lagrangian models based on a modified Germano dynamic procedure, redefined in terms of wavelet thresholding filters, are proposed. These models extend the original path-line formulation of Meneveau et al. [J. Fluid Mech. 319 (1996)] in two ways: as Lagrangian path-line diffusive and Lagrangian path-tube averaging procedures. The proposed models are tested for freely decaying homogeneous turbulence with initial Reλ = 72. It is shown that the SCALES results, obtained with less than 0.4% of the total non-adaptive nodes required for a DNS with the same wavelet solver, closely match reference DNS data. In contrast to classical LES, this agreement holds not only for large scale global statistical quantities, but also for energy and, more importantly, enstrophy spectra up to the dissipative wavenumber range. [ABSTRACT FROM AUTHOR]

Solid organ transplantation is a valuable therapeutic modality for a variety of end-organ diseases. The success of this therapy is largely a consequence of the development of modern immunosuppressive agents. However, these agents also lead to significant side effects that have not reduced the development of chronic rejection. Hence, modalities that induce transplantation tolerance would be of great benefit to solid organ transplant recipients. Most studies that have examined the mechanisms involved in transplantation tolerance have focused on adaptive immunity. Over the last 10 years, there has been an increasingly large appreciation of the importance of the innate immune system in immunological responses. This review will highlight recent experimental articles that investigate the role of the Toll-like receptors, which are critical innate immune receptors, in the induction of transplantation tolerance. [ABSTRACT FROM AUTHOR]

Concerns regarding human milk in our society are diverse, ranging from the presence of environmental chemicals to the health of breastfed infants and the economic value of breastfeeding to society. The panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on 24–26 September 2004, considered how human milk research may contribute to environmental health initiatives to benefit society. The panel concluded that infant, maternal, and community health can benefit from studies using human milk biomonitoring. Unlike other biological specimens, human milk provides information regarding exposure of the mother and breastfed infant to environmental chemicals. Some of the health topics relevant to this field of research include disorders of growth and development in infants, cancer origins in women, and characterization of the trend of exposure to environmental chemicals in the community. The research focus will determine the design of the study and the need for the collection of alternative biological specimens and the long-term storage of these specimens. In order to strengthen the ability to interpret study results, it is important to identify reference ranges for the chemicals measured and to control for populations with high environmental chemical exposure, because the amount of data on environmental chemical levels in human milk that is available for comparison is extremely limited. In addition, it will be necessary to validate models used to assess infant exposure from breastfeeding because of the variable nature of current models. Information on differences between individual and population risk estimates for toxicity needs to be effectively communicated to the participant. Human milk research designed to answer questions regarding health will require additional resources to meet these objectives. [ABSTRACT FROM AUTHOR]

This article presents the conclusions and recommendations of the expert panel for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the U.S. and held at the Hershey S. Medical Center in Pennsylvania State University College of Medicine on September 24-26, 2004. The Technical Workshop focused on questions related to interpretation of information gathered from human milk biomonitoring studies. Biomonitoring can measure a person's exposure to a chemical in his/her tissue. It is noted here that many of the conclusions and research needs enumerated by the panel from the first workshop remain important and relevant.

In this work coherent vortex simulation (CVS) and stochastic coherent adaptive large eddy simulation (SCALES) simulations of decaying incompressible isotropic turbulence are compared to DNS and large eddy simulation (LES) results. Current LES relies on, at best, a zonally adapted filter width to reduce the computational cost of simulating complex turbulent flows. While there is an improvement over a uniform filter width, this approach has two limitations. First, it does not capture the high wave number components of the coherent vortices that make up the organized part of turbulent flows, thus losing essential physical information. Secondly, the flow is over-resolved in the regions between the coherent vortices, thus wasting computational resources. The SCALES approach addresses these shortcomings of LES by using a dynamic grid adaptation strategy that is able to resolve and track the most energetic coherent structures in a turbulent flow field. This corresponds to a dynamically adaptive local filter width. Unlike CVS, which we show is able to recover low order statistics with no subgrid scale (SGS) stress model, the higher compression used in SCALES necessitates that the effect of the unresolved SGS stresses must be modeled. These SGS stresses are approximated using a new dynamic eddy viscosity model based on Germano's classical dynamic procedure redefined in terms of two wavelet thresholding filters. [ABSTRACT FROM AUTHOR]

Glyphosate is among the pesticides most frequently reported to the California EPA Pesticide Illness Surveillance Program. We analyzed glyphosate-related calls to the Pesticide Illness Surveillance Program in order to assess the number of reports involving systemic symptoms and to better understand the nature and severity of reported cases. Data on glyphosate and other pesticides are available for the years 1982–1997 including: type of exposure (agricultural/other); target organ(s) affected (skin/eye/respiratory/systemic); exposure(s); an assessment of causal relationship (possible, probable, or definite); and limited medical text. Of 815 total glyphosate calls, most involved topical irritation of the eye (n=399), skin (n=250), upper airway (n=7), or combinations of these sites (n=32) without systemic symptoms. Of the 187 systemic cases, only 22 had symptoms recorded as probably or definitely related to glyphosate exposure alone. The reported symptoms were not severe, expected to be limited in duration, and frequently inconsistent with the route of exposure and/or previous experience with glyphosate. We conclude that call volume is not a reliable indicator of the actual incidence or severity of glyphosate-related incidents in California. [ABSTRACT FROM AUTHOR]

Scientific discovery has long been explained in terms of theory, data, and little else. We propose a new approach to scientific discovery in which tools play a central role by suggesting themselves as scientific theories, by way of what we call the tools-to-theories heuristic of scientific discovery. In this article, we extend our previous analysis of statistical tools that became theories of mind to the computer and its impact on psychological theorizing. We first show how a conceptual separation of intelligence and calculation in the early 19th century made mechanical computation, and later the electronic computer, conceivable. We next show how in this century, when computers finally became standard laboratory tools, the computer was proposed—and eventually adopted—as a model of mind. Thus, we travel the full circle from mind to computer and back. [ABSTRACT FROM AUTHOR]