331 research outputs found

    Float processing of high-temperature complex silicate glasses and float baths used for same

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    A float glass process for production of high melting temperature glasses utilizes a binary metal alloy bath having the combined properties of a low melting point, low reactivity with oxygen, low vapor pressure, and minimal reactivity with the silicate glasses being formed. The metal alloy of the float medium is exothermic with a solvent metal that does not readily form an oxide. The vapor pressure of both components in the alloy is low enough to prevent deleterious vapor deposition, and there is minimal chemical and interdiffusive interaction of either component with silicate glasses under the float processing conditions. Alloys having the desired combination of properties include compositions in which gold, silver or copper is the solvent metal and silicon, germanium or tin is the solute, preferably in eutectic or near-eutectic compositions

    Management Strategies for the Control of Soybean Rust

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    The identification of Asian soybean rust in Paraguay in 2001(Morel and Yorinori, 2002) and its spread to over 90% of the soybean production in Brazil through the 2003 season has heightened the awareness that this disease will soon be a threat to production on the continental USA. With the yield losses this disease can cause it will have a big impact on the profitability of soybean production

    Posttranscriptional regulation controls calretinin expression in malignant pleural mesothelioma

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    Calretinin (CALB2) is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM). We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide) 3′ untranslated region (3′UTR) predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE) in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3′UTR in the posttranscriptional regulation of calretinin expression in MPM. CALB2-3′UTR was inserted downstream of the luciferase reporter gene using pmiRGLO vector and reporter expression was determined after transfection into MPM cells. Targeted mutagenesis was used to generate variants harboring mutated miR-30 family and ARE binding sites. Electrophoretic mobility shift assay was used to test for the presence of ARE binding proteins. CALB2-3′UTR significantly decreased luciferase activity in MPM cells. Analysis of mutation in the ARE site revealed a further destabilization of the reporter and human antigen R (HuR) binding to the ARE sequence was detected. The mutation of two miR-30 binding sites abolished CALB2-3′UTR destabilization effect; a transient delivery of miR-30e-5p mimics or anti-miR into MPM cells resulted in a significant decrease/increase of the luciferase reporter expression and calretinin protein, respectively. Moreover, overexpression of CALB2-3′UTR quenched the effect of miR-30e-5p mimics on calretinin protein levels, possibly by sequestering the mimics, thereby suggesting a competitive endogenous RNA network. Finally, by data mining we observed that expression of miR-30e-5p was negatively correlated with the calretinin expression in a cohort of MPM patient samples. Our data show the role of (1) adenine-uridine (AU)-binding proteins in calretinin stabilization and (2) miR-30e-5p in the posttranscriptional negative regulation of calretinin expression via interaction with its 3′UTR. Furthermore, our study demonstrates a possible physiological role of calretinin’s alternatively spliced transcripts

    for Cancer Research-Cancer Institute,

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    Cell-free microRNAs: potential biomarkers in need o

    Effect of electronic medication reconciliation at the time of hospital discharge on inappropriate medication use in the community: an interrupted time-series analysis

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    BACKGROUND: It is unclear if enhanced electronic medication reconciliation systems can reduce inappropriate medication use and improve patient care. We evaluated trends in potentially inappropriate medication use after hospital discharge before and after adoption of an electronic medication reconciliation system. METHODS: We conducted an interrupted time-series analysis in 3 tertiary care hospitals in London, Ontario, using linked health care data (2011-2019). We included patients aged 66 years and older who were discharged from hospital. Starting between Apr. 13 and May 21, 2014, physicians were required to complete an electronic medication reconciliation module for each discharged patient. As a process outcome, we evaluated the proportion of patients who continued to receive a benzodiazepine, antipsychotic or gastric acid suppressant as an outpatient when these medications were first started during the hospital stay. The clinical outcome was a return to hospital within 90 days of discharge with a fall or fracture among patients who received a new benzodiazepine or antipsychotic during their hospital stay. We used segmented linear regression for the analysis. RESULTS: We identified 15 932 patients with a total of 18 405 hospital discharge episodes. Before the implementation of the electronic medication reconciliation system, 16.3% of patients received a prescription for a benzodiazepine, antipsychotic or gastric acid suppressant after their hospital stay. After implementation, there was a significant and immediate 7.0% absolute decline in this proportion (95% confidence interval [CI] 4.5% to 9.5%). Before implementation, 4.1% of discharged patients who newly received a benzodiazepine or antipsychotic returned to hospital with a fracture or fall within 90 days. After implementation, there was a significant and immediate 2.3% absolute decline in this outcome (95% CI 0.3% to 4.3%). INTERPRETATION: Implementation of an electronic medication reconciliation system in 3 tertiary care hospitals reduced potentially inappropriate medication use and associated adverse events when patients transitioned back to the community. Enhanced electronic medication reconciliation systems may allow other hospitals to improve patient safety

    Validation of predictive equations to estimate resting metabolic rate of females and males across different activity levels

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    ACKNOWLEDGMENTS The authors are sincerely grateful to all the volunteers involved in this experimental study. This research was performed in the Human Integrative Physiology Laboratory (Dept. of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, USA). OPN is funded by a Virginia Tech Presidential Postdoctoral Fellowship, KHR by a Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education Predoctoral Fellow-ship, and GZR is funded by Next Generation EU funds Margarita Salas Postdoctoral Fellowship. FUNDING INFORMATION OPN is funded by a Virginia Tech Presidential Postdoctoral Fellowship, and KHR by a Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education Predoctoral FellowshipPeer reviewedPublisher PD

    Integrating administrative and clinical datasets to improve patient outcomes.

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    Integrating electronic health records (EHR) with health administrative data offer opportunities for enhanced decision support, health systems evaluations and research for improved patient care. We describe the process of integrating EHR data from 12 hospitals in Southwestern Ontario, Canada and present a health systems evaluation enabled by this linkage. With support and buy-in from the hospital Chief Executive Officers, a data sharing agreement (DSA) with ICES was executed, outlining the process to approve data transfer requests. Due to the complexity and volume of the EHR, complete data were not immediately transferred to ICES; instead, a project subcommittee comprising of physician leadership, local and regional privacy and risk officers, and ICES staff was assembled to review and approve project-specific data integration requests. An evaluation of the adoption of an electronic medication reconciliation system within the EHR on potentially inappropriate prescribing after hospital discharge was conducted using interrupted time-series analyses. The data integration request process begins with confirmation of data availability and accuracy within the EHR, enabled by a dedicated health information analyst and institutional decision support teams. Once data feasibility is confirmed, project rationale is submitted to the project subcommittee approval. Following approval, the request undergoes privacy and legal assessment as per the DSA and a project-ready dataset is submitted for linkage. An evaluation of the adoption of an electronic medication reconciliation system demonstrated an immediate and dramatic reduction in inappropriate medication prescribing and associated adverse events such as a fall or fracture among elderly patients discharged following acute inpatient stays. Administrative data are valuable at assessing population-based health, but often lack key clinical information present in EHRs. Integrating both data sources offers a more comprehensive picture of patient care and allows for robust analyses. Rigorous investigations generate trusted evidence for decision makers to inform policy and quality improvements within the healthcare system

    The importance of RT-qPCR primer design for the detection of siRNA-mediated mRNA silencing

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    <p>Abstract</p> <p>Background</p> <p>The use of RNAi to analyse gene function <it>in vitro </it>is now widely applied in biological research. However, several difficulties are associated with its use <it>in vivo</it>, mainly relating to inefficient delivery and non-specific effects of short RNA duplexes in animal models. The latter can lead to false positive results when real-time RT-qPCR alone is used to measure target mRNA knockdown.</p> <p>Findings</p> <p>We observed that detection of an apparent siRNA-mediated knockdown <it>in vivo </it>was dependent on the primers used for real-time RT-qPCR measurement of the target mRNA. Two siRNAs specific for <it>RRM1 </it>with equivalent activity <it>in vitro </it>were administered to A549 xenografts via intratumoural injection. In each case, apparent knockdown of <it>RRM1 </it>mRNA was observed only when the primer pair used in RT-qPCR flanked the siRNA cleavage site. This false-positive result was found to result from co-purified siRNA interfering with both reverse transcription and qPCR.</p> <p>Conclusions</p> <p>Our data suggest that using primers flanking the siRNA-mediated cleavage site in RT-qPCR-based measurements of mRNA knockdown <it>in vivo </it>can lead to false positive results. This is particularly relevant where high concentrations of siRNA are introduced, particularly via intratumoural injection, as the siRNA may be co-purified with the RNA and interfere with downstream enzymatic steps. Based on these results, using primers flanking the siRNA target site should be avoided when measuring knockdown of target mRNA by real-time RT-qPCR.</p
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