59 research outputs found

    Analysis of Hydrologic Data for the White River Basin

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    The value of the natural resources of the White River Basin (Basin), AR is recognized by the area's designation as a "Wetland of International Importance". The Basin constitutes one of the Nation's largest remaining intact forested wetland landscapes, second only to the Atchafalya Basin. It supports the North American continent's largest concentration of over-wintering mallard ducks, a world-class trout fishery, the last vestige of a big river fishery remaining in the Mississippi River Basin, and numerous threatened and endangered species. The continued viability of this wetland ecosystem depends on the suitability of the hydrologic environment to the resident flora and fauna. Numerous modifications of the Basin hydrologic features in the past century have seriously impaired the sustainability of these resources. The Basinwide alterations of hydrologic processes (e.g., impoundment and regulatory releases of flows and volumes in the upper reaches, navigational modifications of lower reaches, and consumptive demands for agricultural use throughout) have affected the hydrology of the system profoundly. The result is highly regulated flows and stages, vastly altered hydrologic patterns, over-stabilized water levels, and disruption of seasonal water distribution patterns. Given the critical nature of hydrology in regulating the structure and function of wetland ecosystems, the impacts have been devastating, particularly to the critical bottomland hardwoods that support the Basin's fish and wildlife resources. To date these piece-meal, system-wide, hydrologic alterations have cornmutatively degraded the habitat value of this resource for fish and wildlife in the Basin, and have lead to changes in their numbers and distributions. In spite of the enormous stakes involved, there has been no comprehensive characterization of the Basin hydrology. System alterations such as channel deepening, dam construction, water allocation plans, and flood control measures are currently pending. These projects will potentially hrther modify the hydrologic environments of the Basin, and no doubt require mitigation measures. In addition, there is genuine interest in restoring aspects of the Basin's historic hydrologic regime within some set of reasonable limits. In order to proceed with this effort, the anticipated effects of these modifications and restorations on the Basin ecology require thorough study of the area's historic hydrology, so that connectivity among Basin precipitation patterns, flow fluctuations, and land use changes can be made. A basin hydrologic characterization is an initial component of this effort. The focus of this effort was to determine and assemble the data set from which characterization of the hydrologic environments of the Basin using historic and recent water level, flow, (primarily by USGS-WRD) at locations throughout the Basin could proceed. ( Document has 11 pages.

    Microdevices and Methods of Manufacture

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    Illustrative embodiments of microdevices and methods of manufacturing such microdevices are disclosed. In at least one illustrative embodiment, a method of manufacturing one or more microdevices may include forming a liquid dispersion containing cellulose nanocrystals (CNC), depositing the liquid dispersion containing the CNC on a substrate, drying the liquid dispersion containing the CNC to form a solid film on the substrate, where the liquid dispersion contains a sufficient concentration of CNC to form a continuous solid film having a controlled microstructure, and processing the solid film to form the one or more microdevices on the substrate

    Microdevices and methods of manufacture

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    Illustrative embodiments of microdevices and methods of manufacturing such microdevices are disclosed. In at least one illustrative embodiment, one or more microdevices may be formed on a substrate, with each of the one or more microdevices comprising a body micromachined from a continuous film formed on the substrate, the continuous film having a controlled microstructure of cellulose nanocrystals (CNC)

    Partial abdominal evisceration and intestinal autotransplantation to resect a mesenteric carcinoid tumor

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    <p>Abstract</p> <p>Background</p> <p>Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia.</p> <p>Case Presentation</p> <p>We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds. While his tumor was thought to be unresectable by conventional techniques, it was successfully resected using intestinal autotransplantation to safely gain access to the tumor. This case is the first described application of this technique to carcinoid tumors.</p> <p>Conclusions</p> <p>Intestinal autotransplantation can be utilized to safely resect mesenteric carcinoid tumors from patients who were not previously thought to be surgical candidates. We review the literature concerning both carcinoid metastases to the intestinal mesentery and the use of intestinal autotransplantation to treat lesions involving the mesenteric root.</p

    Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

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    <p>Abstract</p> <p>Background</p> <p>Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.</p> <p>Methods</p> <p>A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.</p> <p>Results</p> <p>A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.</p> <p>Conclusions</p> <p>Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.</p

    Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts

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    To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

    In Situ-Targeting of Dendritic Cells with Donor-Derived Apoptotic Cells Restrains Indirect Allorecognition and Ameliorates Allograft Vasculopathy

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    Chronic allograft vasculopathy (CAV) is an atheromatous-like lesion that affects vessels of transplanted organs. It is a component of chronic rejection that conventional immuno-suppression fails to prevent, and is a major cause of graft loss. Indirect allo-recognition through T cells and allo-Abs are critical during CAV pathogenesis. We tested whether the indirect allo-response and its impact on CAV is down-regulated by in situ-delivery of donor Ags to recipient's dendritic cells (DCs) in lymphoid organs in a pro-tolerogenic fashion, through administration of donor splenocytes undergoing early apoptosis. Following systemic injection, donor apoptotic cells were internalized by splenic CD11chi CD8α+ and CD8− DCs, but not by CD11cint plasmacytoid DCs. Those DCs that phagocytosed apoptotic cells in vivo remained quiescent, resisted ex vivo-maturation, and presented allo-Ag for up to 3 days. Administration of donor apoptotic splenocytes, unlike cells alive, (i) promoted deletion, FoxP3 expression and IL-10 secretion, and decreased IFN-γ-release in indirect pathway CD4 T cells; and (ii) reduced cross-priming of anti-donor CD8 T cells in vivo. Targeting recipient's DCs with donor apoptotic cells reduced significantly CAV in a fully-mismatched aortic allograft model. The effect was donor specific, dependent on the physical characteristics of the apoptotic cells, and was associated to down-regulation of the indirect type-1 T cell allo-response and secretion of allo-Abs, when compared to recipients treated with donor cells alive or necrotic. Down-regulation of indirect allo-recognition through in situ-delivery of donor-Ag to recipient's quiescent DCs constitutes a promising strategy to prevent/ameliorate indirect allorecognition and CAV

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
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