728 research outputs found

    bGWAS: an R package to perform Bayesian genome wide association studies.

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    Increasing sample size is not the only strategy to improve discovery in Genome Wide Association Studies (GWASs) and we propose here an approach that leverages published studies of related traits to improve inference. Our Bayesian GWAS method derives informative prior effects by leveraging GWASs of related risk factors and their causal effect estimates on the focal trait using multivariable Mendelian randomization. These prior effects are combined with the observed effects to yield Bayes Factors, posterior and direct effects. The approach not only increases power, but also has the potential to dissect direct and indirect biological mechanisms. bGWAS package is freely available under a GPL-2 License, and can be accessed, alongside with user guides and tutorials, from https://github.com/n-mounier/bGWAS. Supplementary data are available at Bioinformatics online

    Phase II study of paclitaxel combined with capecitabine as second-line treatment for advanced gastric carcinoma after failure of cisplatin-based regimens

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    Purpose To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. Methods Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m2 twice daily (1,650 mg/m2 per day) on days 1–14 and paclitaxel 175 mg/m2 by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. Results Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41–84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2–55.7%) with one complete response and 42.3% (95%CI = 17.2–55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4–4.5 months). Median overall survival was 7.5 months (95%CI = 6–10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11–18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). Conclusions Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts

    Structural variant calling: the long and the short of it.

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    Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, and large-scale chromosome evolution-giving rise to the differences within populations and among species. Nevertheless, characterizing SVs and determining the optimal approach for a given experimental design remains a computational and scientific challenge. Multiple approaches have emerged to target various SV classes, zygosities, and size ranges. Here, we review these approaches with respect to their ability to infer SVs across the full spectrum of large, complex variations and present computational methods for each approach

    BLOOD GLUCOSE LOWERING EFFECT OF AQUEOUS LEAF EXTRACTS OF AGERATUM CONYZOIDES IN RATS.

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    This study was undertaken to investigate the effect of aqueous extracts from leaves of Ageratum conyzoides (300mg/kg) on blood glucose in normoglycemic and streptozotocin-diabetic rats. The extract was administered orally and the blood glucose level was measured hourly for 4h. The hypoglycaemic activity was evaluated by comparing with the initial blood glucose level. In streptozotocin-diabetic rats, the aqueous extract from leaves of Ageratum conyzoides showed a significant reduction of blood glucose level of 9.5% after 1hour and 21.3% after 4 hour

    The value of demonstration projects for new interventions: The case of human papillomavirus vaccine introduction in low- and middle-income countries.

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    Demonstration projects or pilots of new public health interventions aim to build learning and capacity to inform country-wide implementation. Authors examined the value of HPV vaccination demonstration projects and initial national programmes in low-income and lower-middle-income countries, including potential drawbacks and how value for national scale-up might be increased. Data from a systematic review and key informant interviews, analyzed thematically, included 55 demonstration projects and 8 national programmes implemented between 2007-2015 (89 years' experience). Initial demonstration projects quickly provided consistent lessons. Value would increase if projects were designed to inform sustainable national scale-up. Well-designed projects can test multiple delivery strategies, implementation for challenging areas and populations, and integration with national systems. Introduction of vaccines or other health interventions, particularly those involving new target groups or delivery strategies, needs flexible funding approaches to address specific questions of scalability and sustainability, including learning lessons through phased national expansion

    HPV vaccine introduction in Rwanda: Impacts on the broader health system.

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    OBJECTIVES: Rwanda was the first country in Africa to introduce the human papillomavirus (HPV) vaccine. This was achieved through multi-year school-based campaigns. Our study evaluated the impact of the HPV vaccine introduction on the country's immunisation programme and health system. METHODS: Thirty key informants were interviewed at national and district levels, and in participating schools. Twenty-seven health facilities completed a questionnaire exploring the effects of the new vaccine introduction on six health system building blocks, as defined by the World Health Organization. Routine service activity data were collected during a 90-day period around the introduction. RESULTS: Routine vaccination activities were not disrupted during the delivery, likely due to a strong Expanded Program on Immunization, appropriate planning and a well-resourced operation. Opportunities were seized to co-deliver other interventions targeted at children and adolescents, such as health promotion. Collaboration with the Ministry of Education was strengthened at national level. Although there were some temporary increases in staff workload, no major negative effects were reported. CONCLUSION: Despite its delivery through school-based campaigns, the HPV vaccine integrated well into the immunisation programme and health system. The introduction had no major negative effects. Some opportunities were seized to expand services and collaborations

    Direct Observation of Propagating Gigahertz Coherent Guided Acoustic Phonons in Free Standing Single Copper Nanowires

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    We report on gigahertz acoustic phonon waveguiding in free-standing single copper nanowires studied by femtosecond transient reflectivity measurements. The results are discussed on the basis of the semianalytical resolution of the Pochhammer and Chree equation. The spreading of the generated Gaussian wave packet of two different modes is derived analytically and compared with the observed oscillations of the sample reflectivity. These experiments provide a unique way to independently obtain geometrical and material characterization. This direct observation of coherent guided acoustic phonons in a single nano-object is also the first step toward nanolateral size acoustic transducer and comprehensive studies of the thermal properties of nanowires
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