Pultrusion Die Assembly

This invention relates generally to pultrusion die assemblies, and more particularly, to a pultrusion die assembly which incorporates a plurality of functions in order to produce a continuous, thin composite fiber reinforced thermoplastic material. The invention is useful for making high performance thermoplastic composite materials in sheets which can be coiled on a spool and stored for further processing

Probabilities of Large Earthquakes in the San Francisco Bay Region, California

In 1987 a Working Group on California Earthquake Probabilities was organized by the U.S. Geological Survey at the recommendation of the National Earthquake Prediction Evaluation Council (NEPEC). The membership included representatives from private industry, academia, and the U.S. Geological Survey. The Working Group computed long-term probabilities of earthquakes along the major faults of the San Andreas fault system on the basis of consensus interpretations of information then available. Faults considered by the Working Group included the San Andreas fault proper, the San Jacinto and Imperial-faults of southern California, and the Hayward fault of northern California. The Working Group issued a final report of its findings in 1988 (Working Group, 1988) that was reviewed and endorsed by NEPEC. As a consequence of the magnitude 7.1 Loma Prieta, California, earthquake of October 17, 1989, a second Working Group on California Earthquake Probabilities was organized under the auspices of NEPEC. Its charge was to review and, as necessary, revise the findings of the 1988 report on the probability of large earthquakes in the San Francisco Bay region. In particular, the Working Group was requested to examine the probabilities of large earthquakes in the context of new interpretations or physical changes resulting from the Loma Prieta earthquake. In addition, it was to consider new information pertaining to the San Andreas and other faults in the region obtained subsequent to the release of the 1988 report. Insofar as modified techniques and improved data have been used in this study, the same approach might also, of course, modify the probabilities for southern California. This reevaluation has, however, been specifically limited to the San Francisco Bay region. This report is intended to summarize the collective knowledge and judgments of a diverse group of earthquake scientists to assist in formulation of rational earthquake policies. A considerable body of information about active faults in the San Francisco Bay region leads to the conclusion that major earthquakes are likely within the next tens of years. Several techniques can be used to compute probabilities of future earthquakes, although there are uncertainties about the validity of specific assumptions or models that must be made when applying these techniques. The body of this report describes the data and detailed assumptions that lead to specific probabilities for different fault segments. Additional data and future advances in our understanding of earthquake physics may alter the way that these probabilities are estimated. Even though this uncertainty must be acknowledged, we emphasize that the findings of this report are supported by other lines of argument and are consistent with our best understanding of the likelihood for the occurrence of earthquakes in the San Francisco Bay region

Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials.</p> <p>Methods</p> <p>The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For <it>in vivo </it>studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired <it>t </it>test using GraphPad prism software.</p> <p>Results</p> <p>Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug concentrations, there was no effect on phosphorylated pools at drug combinations that were synergistic. The amount of troxacitabine incorporated into DNA was also not affected by the presence of gemcitabine. <it>In vivo </it>testing against a human pancreatic (AsPC-1) xenograft mouse tumor model indicated that both drugs were more than additive at well-tolerated doses and schedule. The biological basis for this synergy is unclear as we did not observe changes in apoptosis, DNA repair, troxacitabine incorporation into DNA or troxacitabine metabolism in the presence of gemcitabine.</p> <p>Conclusion</p> <p>These data, together with phase I clinical data showing tolerability of both agents when combined, suggest combination therapy with troxacitabine and gemcitabine warrants further evaluation in advanced pancreatic cancer patients.</p

Does Cultural Competency Training of Health Professionals Improve Patient Outcomes? A Systematic Review and Proposed Algorithm for Future Research

BACKGROUND: Cultural competency training has been proposed as a way to improve patient outcomes. There is a need for evidence showing that these interventions reduce health disparities. OBJECTIVE: The objective was to conduct a systematic review addressing the effects of cultural competency training on patient-centered outcomes; assess quality of studies and strength of effect; and propose a framework for future research. DESIGN: The authors performed electronic searches in the MEDLINE/PubMed, ERIC, PsycINFO, CINAHL and Web of Science databases for original articles published in English between 1990 and 2010, and a bibliographic hand search. Studies that reported cultural competence educational interventions for health professionals and measured impact on patients and/or health care utilization as primary or secondary outcomes were included. MEASUREMENTS: Four authors independently rated studies for quality using validated criteria and assessed the training effect on patient outcomes. Due to study heterogeneity, data were not pooled; instead, qualitative synthesis and analysis were conducted. RESULTS: Seven studies met inclusion criteria. Three involved physicians, two involved mental health professionals and two involved multiple health professionals and students. Two were quasi-randomized, two were cluster randomized, and three were pre/post field studies. Study quality was low to moderate with none of high quality; most studies did not adequately control for potentially confounding variables. Effect size ranged from no effect to moderately beneficial (unable to assess in two studies). Three studies reported positive (beneficial) effects; none demonstrated a negative (harmful) effect. CONCLUSION: There is limited research showing a positive relationship between cultural competency training and improved patient outcomes, but there remains a paucity of high quality research. Future work should address challenges limiting quality. We propose an algorithm to guide educators in designing and evaluating curricula, to rigorously demonstrate the impact on patient outcomes and health disparities

A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes.</p> <p>Methods/Design</p> <p>A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates.</p> <p>Discussion</p> <p>Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic.</p> <p>Trial Registration Number</p> <p><a href="http://www.controlled-trials.com/ISRCTN45190901">ISRCTN45190901</a></p

Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs