A cross-sectional survey of supports for evidence-informed decision-making in healthcare organisations: a research protocol

Background: This protocol builds on the development of a) a framework that identified the various supports (i.e. positions, activities, interventions) that a healthcare organisation or health system can implement for evidence-informed decision-making (EIDM) and b) a qualitative study that showed the current mix of supports that some Canadian healthcare organisations have in place and the ones that are perceived to facilitate the use of research evidence in decision-making. Based on these findings, we developed a web survey to collect cross-sectional data about the specific supports that regional health authorities and hospitals in two Canadian provinces (Ontario and Quebec) have in place to facilitate EIDM. Methods/design This paper describes the methods for a cross-sectional web survey among 32 regional health authorities and 253 hospitals in the provinces of Quebec and Ontario (Canada) to collect data on the current mix of organisational supports that these organisations have in place to facilitate evidence-informed decision-making. The data will be obtained through a two-step survey design: a 10-min survey among CEOs to identify key units and individuals in regard to our objectives (step 1) and a 20-min survey among managers of the key units identified in step 1 to collect information about the activities performed by their unit regarding the acquisition, assessment, adaptation and/or dissemination of research evidence in decision-making (step 2). The study will target three types of informants: CEOs, library/documentation centre managers and all other key managers whose unit is involved in the acquisition, assessment, adaptation/packaging and/or dissemination of research evidence in decision-making. We developed an innovative data collection system to increase the likelihood that only the best-informed respondent available answers each survey question. The reporting of the results will be done using descriptive statistics of supports by organisation type and by province. Discussion This study will be the first to collect and report large-scale cross-sectional data on the current mix of supports health system organisations in the two most populous Canadian provinces have in place for evidence-informed decision-making. The study will also provide useful information to researchers on how to collect organisation-level data with reduced risk of self-reporting bias

Genetic diversity and phylogeny of Aedes aegypti, the main arbovirus vector in the Pacific

Background The Pacific region is an area unique in the world, composed of thousands of islands with differing climates and environments. The spreading and establishment of the mosquito Aedes aegypti in these islands might be linked to human migration. Ae. aegypti is the major vector of arboviruses (dengue, chikungunya and Zika viruses) in the region. The intense circulation of these viruses in the Pacific during the last decade led to an increase of vector control measures by local health authorities. The aim of this study is to analyze the genetic relationships among Ae. aegypti populations in this region. Methodology/Principal Finding We studied the genetic variability and population genetics of 270 Ae. aegypti, sampled from 9 locations in New Caledonia, Fiji, Tonga and French Polynesia by analyzing nine microsatellites and two mitochondrial DNA regions (CO1 and ND4). Microsatellite markers revealed heterogeneity in the genetic structure between the western, central and eastern Pacific island countries. The microsatellite markers indicate a statistically moderate differentiation (FST = 0.136; P < = 0.001) in relation to island isolation. A high degree of mixed ancestry can be observed in the most important towns (e.g. Noumea, Suva and Papeete) compared with the most isolated islands (e.g. Ouvea and Vaitahu). Phylogenetic analysis indicated that most of samples are related to Asian and American specimens. Conclusions/Significance Our results suggest a link between human migrations in the Pacific region and the origin of Ae. aegypti populations. The genetic pattern observed might be linked to the island isolation and to the different environmental conditions or ecosystems

Analysis of CATMA transcriptome data identifies hundreds of novel functional genes and improves gene models in the Arabidopsis genome

<p>Abstract</p> <p>Background</p> <p>Since the finishing of the sequencing of the <it>Arabidopsis thaliana </it>genome, the Arabidopsis community and the annotator centers have been working on the improvement of gene annotation at the structural and functional levels. In this context, we have used the large CATMA resource on the Arabidopsis transcriptome to search for genes missed by different annotation processes. Probes on the CATMA microarrays are specific gene sequence tags (GSTs) based on the CDS models predicted by the Eugene software. Among the 24 576 CATMA v2 GSTs, 677 are in regions considered as intergenic by the TAIR annotation. We analyzed the cognate transcriptome data in the CATMA resource and carried out data-mining to characterize novel genes and improve gene models.</p> <p>Results</p> <p>The statistical analysis of the results of more than 500 hybridized samples distributed among 12 organs provides an experimental validation for 465 novel genes. The hybridization evidence was confirmed by RT-PCR approaches for 88% of the 465 novel genes. Comparisons with the current annotation show that these novel genes often encode small proteins, with an average size of 137 aa. Our approach has also led to the improvement of pre-existing gene models through both the extension of 16 CDS and the identification of 13 gene models erroneously constituted of two merged CDS.</p> <p>Conclusion</p> <p>This work is a noticeable step forward in the improvement of the Arabidopsis genome annotation. We increased the number of Arabidopsis validated genes by 465 novel transcribed genes to which we associated several functional annotations such as expression profiles, sequence conservation in plants, cognate transcripts and protein motifs.</p

Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma

Protein families encoded by transcripts that are differentially spliced in various types of HCC. Table S2. Bioinformatical prediction of functional changes caused by some of ASEs identified. Table S3. List of tumor suppressors for which AS is dysregulated in various types of HCC. Table S4. List of oncogenes for which AS is dysregulated in various types of HCC. Table S5. List of kinases for which AS is dysregulated in various types of HCC. Table S6. List of transcription factors for which AS is dysregulated in various types of HCC. Table S7. List of genes for which AS is dysregulated in all types of HCC. Table S8. List of genes uniquely dysregulated in HBV-associated HCC. Table S9. List of genes uniquely dysregulated in HCV-associated HCC. Table S10. List of genes uniquely dysregulated in HBV&HCV-associated HCC. Table S11. List of genes uniquely dysregulated in virus-free HCC. Figure S1. Characterization of splicing mysregulation in HCC. Figure S2. Characterization of ASEs that are modified in HBV- and HCV-associated HCC. Figure S3. AS modifications in transcripts encoded by kinases and transcriptions factores in HBV- and HCV-associated HCC. Figure S4. Global profiling of ASE modifications in both HBV&HCV-associated HCC and virus-free-associated HCC. Figure S5. RNA splicing factors in HCC. Figure S6. Modifications to AS of 96 transcripts in response to knockdown of splicing factors with specific siRNAs (PDF 6675 kb

Physical activity mediates the relationship between outdoor time and mental health

Both spending time outdoors and participating in physical activity improve mental health. Given that the outdoor environment provides an ideal location for physical activity, better understanding of the relationships among time spent outdoors, physical activity and positive mental health is needed to help guide interventions. The aim was to examine if physical activity moderates or mediates the relationship between outdoor time and positive mental health. Two-hundred-forty-two participants (15 ± 1 years old, 59% girls) from New Brunswick, Canada were included in the current analysis. Youth self-reported time spent outdoors and moderate-to-vigorous physical activity (MVPA) three times between October 2016 and June 2017. Data on their mental health were collected in October 2017. Values of outdoor time and MVPA were averaged across the three time points to represent the exposure and mediator variables, respectively. Mental health, dichotomized as flourishing/not flourishing, was the outcome in the mediation analysis. An interaction term tested if the mediation effect depended on outdoor time. Analyses were undertaken in 2019 using the mediation package in R. In univariate analyses, both MVPA (p < 0.001) and outdoor time (p = 0.05) were positive predictors of flourishing mental health. In mediation analyses, a small indirect mediation (OR: 1.02, 95% CI: 1.01–1.04) and no direct (1.00, 0.98–1.05) effect were noted, suggesting that MVPA mediates the effect of outdoor time on positive mental health. This effect did not vary as a function of outdoor time (interaction: 1.00, 0.99–1.01). Physical activity mediates the relationship between outdoor time and positive mental health. Outdoor time could promote positive mental health among youth through increases in physical activity

Experimental study and numerical reproduction of self-weight consolidation behavior of thickened tailings

Abstract: Thickened tailings, defined as mineral wastes that behave as a non-Newtonian fluid, show a small yield stress and release a small amount of water following deposition. Thickening has become an increasingly used option in tailings management. This paper presents a detailed examination of gold mine thickened tailings undergoing self-weight consolidation, which is an important mechanism affecting soft soils immediately after deposition. Self-weight consolidation was evaluated using a column equipped with water pressure transmitters whereas a slurry consolidometer was employed to obtain the compressibility relationship under low vertical effective stresses. The piecewise-linear model CS2 was used to model the experimental self-weight consolidation test. This model proved very accurate in reproducing the observed behavior. Both the test results and the model results also confirmed the absence of sedimentation in the thickened tailings, which is in agreement with values reported in the literature related to similar materials

Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement

Background: The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in TTC7A have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. Objectives: This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. Methods: Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. Results: We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. Conclusions: These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.</p