6,197 research outputs found

    Independent Orbiter Assessment (IOA): Analysis of the orbiter main propulsion system

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    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items (PCIs). To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results for the Orbiter Main Propulsion System (MPS) hardware are documented. The Orbiter MPS consists of two subsystems: the Propellant Management Subsystem (PMS) and the Helium Subsystem. The PMS is a system of manifolds, distribution lines and valves by which the liquid propellants pass from the External Tank (ET) to the Space Shuttle Main Engines (SSMEs) and gaseous propellants pass from the SSMEs to the ET. The Helium Subsystem consists of a series of helium supply tanks and their associated regulators, check valves, distribution lines, and control valves. The Helium Subsystem supplies helium that is used within the SSMEs for inflight purges and provides pressure for actuation of SSME valves during emergency pneumatic shutdowns. The balance of the helium is used to provide pressure to operate the pneumatically actuated valves within the PMS. Each component was evaluated and analyzed for possible failure modes and effects. Criticalities were assigned based on the worst possible effect of each failure mode. Of the 690 failure modes analyzed, 349 were determined to be PCIs

    Association between insulin monotherapy versus insulin plus metformin and the risk of all-cause mortality and other serious outcomes: a retrospective cohort study

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    Aims To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE), and cancer in people with type 2 diabetes treated with insulin. Methods For this retrospective cohort study, people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards were identified from the UK Clinical Practice Research Datalink (≈7% sample of the UK population). The risks of all-cause mortality, MACE and incident cancer were evaluated using multivariable Cox models comparing insulin monotherapy with insulin plus metformin. We accounted for insulin dose. Results 12,020 subjects treated with insulin were identified, including 6,484 treated with monotherapy. There were 1,486 deaths, 579 MACE (excluding those with a history of large vessel disease), and 680 cancer events (excluding those in patients with a history of cancer). Corresponding event rates were 41.5 (95% CI 39.4–43.6) deaths, 20.8 (19.2–22.5) MACE, and 21.6 (20.0–23.3) cancer events per 1,000 person-years. The adjusted hazard ratios (aHRs) for people prescribed insulin plus metformin versus insulin monotherapy were 0.60 (95% CI 0.52–0.68) for all-cause mortality, 0.75 (0.62–0.91) for MACE, and 0.96 (0.80–1.15) for cancer. For patients who were propensity-score matched, the corresponding aHRs for all-cause mortality and cancer were 0.62 (0.52–0.75) and 0.99 (0.78–1.26), respectively. For MACE, the aHR was 1.06 (0.75–1.49) prior to 1,275 days and 1.87 (1.22–2.86) after 1,275 days post-index. Conclusions People with type 2 diabetes treated with insulin plus concomitant metformin had a reduced risk of death and MACE compared with people treated with insulin monotherapy. There was no statistically significant difference in the risk of cancer between people treated with insulin as monotherapy or in combination with metformin

    Attitudes Toward Breast Cancer Genetic Testing in Five Special Population Groups

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    Purpose: This study examined interest in and attitudes toward genetic testing in 5 different population groups. Methods: The survey included African American, Asian American, Latina, Native American, and Appalachian women with varying familial histories of breast cancer. A total of 49 women were interviewed in person. Descriptive and nonparametric statistical techniques were used to assess ethnic group differences. Results: Overall, interest in testing was high. All groups endorsed more benefits than risks. There were group differences regarding endorsement of specific benefits and risks: testing to “follow doctor recommendations” (p=0.017), “concern for effects on family” (p=0.044), “distrust of modern medicine” (p=0.036), “cost” (p=0.025), and “concerns about communication of results to others” (p=0.032). There was a significant inverse relationship between interest and genetic testing cost (p Conclusion: Cost may be an important barrier to obtaining genetic testing services, and participants would benefit by genetic counseling that incorporates the unique cultural values and beliefs of each group to create an individualized, culturally competent program. Further research about attitudes toward genetic testing is needed among Asian Americans, Native Americans, and Appalachians for whom data are severely lacking. Future study of the different Latina perceptions toward genetic testing are encouraged

    Sampling Effects on Gene Expression Data from a Human Tumour Xenograft

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    Human tumour tissue transplanted to and passed through immunodeficient mice as xenografts make powerful  model systems to study tumour biology, in particular to investigate the dynamics of treatment responses,  e.g. to chemotherapeutic agents. Before embarking on large-scale gene expression analysis of chemotherapy  response in human sarcoma xenografts, we investigated the reproducibility of expression  patterns derived from such samples. We compared expression profiles from tumours from the same or different  mice and of various sizes, as well as central and peripheral parts of the same tumours. Twenty-three  microarray hybridisations were performed on cDNA arrays representing 13000 genes, using direct labelling  of target cDNAs. An ANOVA-based linear mixed-effects model was constructed, and variances of  experimental and biological factors contributing to variability were estimated. With our labelling procedure  used, the effect of switching the dyes was pronounced compared to all other factors. We detected a small  variation in gene expression between two tumours in the same mouse as well as between tumours from different  mice. Furthermore, central or peripheral position in the tumour had only moderate influence on the  variability of the expression profiles. The biological variability was comparable to experimental variability  caused by labelling, confirming the importance of both biological and technical replicates. We further  analysed the data by pair-wise Fisher’s linear discriminant method and identified genes that were significantly  differentially expressed between samples taken from peripheral or central parts of the tumours.  Finally, we evaluated the result of pooling biological samples to estimate the recommended number of  arrays and hybridisations for microarray experiments in this model.

    Providers' assessment of a novel interactive health information technology in a pediatric intensive care unit

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    Objective: To explore perceptions of critical care providers about a novel collaborative inpatient health information technology (HIT) in a pediatric intensive care unit (PICU) setting. Methods: This cross-sectional, concurrent mixed methods study was conducted in the PICU of a large midwestern children's hospital. The technology, the Large Customizable Interactive Monitor (LCIM), is a flat panel touch screen monitor that displays validated patient information from the electronic health record. It does not require a password to login and is available in each patient's room for viewing and interactive use by physicians, nurses, and families. Quantitative data were collected via self-administered, standardized surveys, and qualitative data via in-person, semistructured interviews between January and April 2015. Data were analyzed using descriptive statistics and inductive thematic analysis. Results: The qualitative analysis showed positive impacts of the LCIM on providers' workflow, team interactions, and interactions with families. Providers reported concerns regarding perceived patient information overload and associated anxiety and burden for families. Sixty percent of providers thought that LCIM was useful for their jobs at different levels, and almost 70% of providers reported that LCIM improved information sharing and communication with families. The average overall satisfaction score was 3.4 on a 0 to 6 scale, between "a moderate amount" and "pretty much." Discussion and Conclusion: This study provides new insight into collaborative HIT in the inpatient pediatric setting and demonstrates that using such technology has the potential to improve providers' experiences with families and just-in-time access to EHR information in a format more easily shared with families

    Building professional discourse in emerging markets: Language, context and the challenge of sensemaking

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    Using ethnographic evidence from the former Soviet republics, this article examines a relatively new and mainly unobserved in the International Business (IB) literature phenomenon of communication disengagement that manifests itself in many emerging markets. We link it to the deficiencies of the local professional business discourse rooted in language limitations reflecting lack of experience with the market economy. This hampers cognitive coherence between foreign and local business entities, adding to the liability of foreignness as certain instances of professional experience fail to find adequate linguistic expression, and complicates cross-cultural adjustments causing multi-national companies (MNCs) financial losses. We contribute to the IB literature by examining cross-border semantic sensemaking through a retrospectively constructed observational study. We argue that a relative inadequacy of the national professional idiom is likely to remain a feature of business environment in post-communist economies for some time and therefore should be factored into business strategies of MNCs. Consequently, we recommend including discursive hazards in the risk evaluation of international projects

    Donor characteristics and the allocation of aid to climate mitigation finance

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    We make use of a panel dataset of 22 donor countries from 1998 to 2009 to examine the links between donor characteristics and the share of overseas development assistance allocated to climate mitigation finance. We find that donors with a larger green domestic budget tend to allocate a smaller portion of overseas aid to mitigation finance (possibly as a result of a competing interest between spending on domestic environmental projects and international climate projects). The opposite holds for donor countries with better institutions (governance) that have ratified the Kyoto Protocol. We also find important discrepancies when comparing the effects of donor characteristics on committed versus disbursed mitigation finance (as a share of aid). For the latter, only commitment to the Kyoto Protocol appears to be of high statistical significance

    Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin

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    Introduction Insulin analogues have become increasingly popular despite their greater cost compared with human insulin. The aim of this study was to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Methods Open-source data from the four UK prescription pricing agencies from 2000 to 2009 were analysed. Cost was adjusted for inflation and reported in UK pounds at 2010 prices. Results Over the 10-year period, the NHS spent a total of £2732 million on insulin. The total annual cost increased from £156 million to £359 million, an increase of 130%. The annual cost of analogue insulin increased from £18.2 million (12% of total insulin cost) to £305 million (85% of total insulin cost), whereas the cost of human insulin decreased from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). If it is assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin was £625 million. Conclusion Given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin would have resulted in considerable financial savings over the period

    An inter-platform repeatability study investigating real-time amplification of plasmid DNA

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    BACKGROUND: The wide variety of real-time amplification platforms currently available has determined that standardisation of DNA measurements is a fundamental aspect involved in the comparability of results. Statistical analysis of the data arising from three different real-time platforms was conducted in order to assess inter-platform repeatability. On three consecutive days two PCR reaction mixes were used on each of the three amplification platforms – the LightCycler(®), ABI PRISM(® )7700 and Rotor Gene 3000™. Real-time PCR amplification using a fluorogenic 5' exonuclease assay was performed in triplicate on negative controls and DNA plasmid dilutions of 10(8)–10(2 )copies to give a total of 24 reactions per PCR experiment. RESULTS: The results of the statistical analyses indicated that the platform with the most precise repeatability was the ABI PRISM(® )7700 when coupled with the FastStart PCR reaction mix. It was also found that there was no obvious relationship between plasmid copy number and repeatability. An ANOVA approach identified the factors that significantly affected the results, in descending order of magnitude, as: plasmid copy number, platform, PCR reaction mix and day (on which the experiment was performed). CONCLUSION: In order to deliver useful, informative genetic tests, standardisation of real-time PCR detection platforms to provide repeatable, reliable results is warranted. In addition, a better understanding of inter-assay and intra-assay repeatability is required
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