523 research outputs found

    Development of a novel tool for assessing coverage of implementation factors in health promotion program resources

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    This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Katharine B. Richardson Research Award at Children's Mercy Kansas CityNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number F32DK115146Institute of Education Sciences and U.S. Department of Education by grant R305A15027

    Prognostic value of upper respiratory tract microbes in children presenting to primary care with respiratory infections:a prospective cohort study

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    BACKGROUND: The association between upper respiratory tract microbial positivity and illness prognosis in children is unclear. This impedes clinical decision-making and means the utility of upper respiratory tract microbial point-of-care tests remains unknown. We investigated for relationships between pharyngeal microbes and symptom severity in children with suspected respiratory tract infection (RTI). METHODS: Baseline characteristics and pharyngeal swabs were collected from 2,296 children presenting to 58 general practices in Bristol, UK with acute cough and suspected RTI between 2011ā€“2013. Post-consultation, parents recorded the severity of six RTI symptoms on a 0ā€“6 scale daily for ā‰¤28 days. We used multivariable hurdle regression, adjusting for clinical characteristics, antibiotics and other microbes, to investigate associations between respiratory microbes and mean symptom severity on days 2ā€“4 post-presentation. RESULTS: Overall, 1,317 (57%) children with complete baseline, microbiological and symptom data were included. Baseline characteristics were similar in included participants and those lacking microbiological data. At least one virus was detected in 869 (66%) children, and at least one bacterium in 783 (60%). Compared to children with no virus detected (mean symptom severity score 1.52), adjusted mean symptom severity was 0.26 points higher in those testing positive for at least one virus (95% CI 0.15 to 0.38, p<0.001); and was also higher in those with detected Influenza B (0.44, 0.15 to 0.72, p = 0.003); RSV (0.41, 0.20 to 0.60, p<0.001); and Influenza A (0.25, -0.01 to 0.51, p = 0.059). Children positive for Enterovirus had a lower adjusted mean symptom severity (-0.24, -0.43 to -0.05, p = 0.013). Children with detected Bordetella pertussis (0.40, 0.00 to 0.79, p = 0.049) and those with detected Moraxella catarrhalis (-0.76, -1.06 to -0.45, p<0.001) respectively had higher and lower mean symptom severity compared to children without these bacteria. CONCLUSIONS: There is a potential role for upper respiratory tract microbiological point-of-care tests in determining the prognosis of childhood RTIs

    Study Protocol for a Cluster-Randomized Trial of a Bundle of Implementation Support Strategies to Improve the Fidelity of Implementation of Schoolwide Positive Behavioral Interventions and Supports in Rural Schools

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    Background: Improving the implementation of evidence-based interventions is important for population-level impacts. Positive Behavioral Interventions and Supports (PBIS) is effective for improving school climate and studentsā€™ behavioral outcomes, but rural schools often lag behind urban and suburban schools in implementing such initiatives. Methods/Design: This paper describes a Type 3 hybrid implementation-effectiveness trial of Rural School Support Strategies (RS3), a bundle of implementation support strategies selected to improve implementation outcomes in rural schools. In this two-arm parallel group trial, 40 rural public schools are randomized to receive: 1) a series of trainings about PBIS; or 2) an enhanced condition with training plus RS3. The trial was planned for two years, but due to the pandemic has been extended another year. RS3 draws from the Interactive Systems Framework, with a university-based team (support system) that works with a team at each school (school-based delivery system), increasing engagement through strategies such as: providing technical assistance, facilitating school team functioning, and educating implementers. The primary organizational-level outcome is fidelity of implementation, with additional implementation outcomes of feasibility, acceptability, appropriateness, and cost. Staff-level outcomes include perceived climate and self-reported adoption of PBIS core components. Student-level outcomes include disciplinary referrals, academic achievement, and perceived climate. Mediators being evaluated include organizational readiness, school team functioning, and psychological safety. Discussion: The study tests implementation strategies, with strengths including a theory-based design, mixed methods data collection, and consideration of mediational mechanisms. Results will yield knowledge about how to improve implementation of universal prevention initiatives in rural schools

    The histone deacetylase inhibitor sodium valproate causes limited transcriptional change in mouse embryonic stem cells but selectively overrides Polycomb-mediated Hoxb silencing.

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    BACKGROUND: Histone deacetylase inhibitors (HDACi) cause histone hyperacetylation and H3K4 hypermethylation in various cell types. They find clinical application as anti-epileptics and chemotherapeutic agents, but the pathways through which they operate remain unclear. Surprisingly, changes in gene expression caused by HDACi are often limited in extent and can be positive or negative. Here we have explored the ability of the clinically important HDACi valproic acid (VPA) to alter histone modification and gene expression, both globally and at specific genes, in mouse embryonic stem (ES) cells. RESULTS: Microarray expression analysis of ES cells exposed to VPA (1 mM, 8 h), showed that only 2.4% of genes showed a significant, >1.5-fold transcriptional change. Of these, 33% were down-regulated. There was no correlation between gene expression and VPA-induced changes in histone acetylation or H3K4 methylation at gene promoters, which were usually minimal. In contrast, all Hoxb genes showed increased levels of H3K9ac after exposure to VPA, but much less change in other modifications showing bulk increases. VPA-induced changes were lost within 24 h of inhibitor removal. VPA significantly increased the low transcription of Hoxb4 and Hoxb7, but not other Hoxb genes. Expression of Hoxb genes increased in ES cells lacking functional Polycomb silencing complexes PRC1 and PRC2. Surprisingly, VPA caused no further increase in Hoxb transcription in these cells, except for Hoxb1, whose expression increased several fold. Retinoic acid (RA) increased transcription of all Hoxb genes in differentiating ES cells within 24 h, but thereafter transcription remained the same, increased progressively or fell progressively in a locus-specific manner. CONCLUSIONS: Hoxb genes in ES cells are unusual in being sensitive to VPA, with effects on both cluster-wide and locus-specific processes. VPA increases H3K9ac at all Hoxb loci but significantly overrides PRC-mediated silencing only at Hoxb4 and Hoxb7. Hoxb1 is the only Hoxb gene that is further up-regulated by VPA in PRC-deficient cells. Our results demonstrate that VPA can exert both cluster-wide and locus-specific effects on Hoxb regulation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Tracking elusive and shifting identities of the global fishing fleet

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    Illegal, unreported, and unregulated (IUU) fishing costs billions of dollars per year and is enabled by vessels obfuscating their identity. Here, we combine identities of ~35,000 vessels with a decade of GPS data to provide a global assessment of fishing compliance, reflagging patterns, and fishing by foreign-owned vessels. About 17% of high seas fishing is by potentially unauthorized or internationally unregulated vessels, with hot spots of this activity in the west Indian and the southwest Atlantic Oceans. In addition, reflagging, a tactic often used to obscure oversight, occurs in just a few ports primarily by fleets with high foreign ownership. Fishing by foreign-owned vessels is concentrated in parts of high seas and certain national waters, often flying flags of convenience. These findings can address the global scope of potential IUU fishing and enable authorities to improve oversight

    Shape controlled assembly of carboxylic acids : formation of a binary monolayer by intercalation into molecular nanotunnels

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    Support by the Leverhulme Trust (RGP -2013-177) and EPSRC via doctoral training grants (R .O .d.l.M .,H.A.) and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) (PhD studentship to K.T.) is gratefully acknowledged. A. A. acknowledges the financial support by the DAAD-Aceh Scholarship of Excellence.Binary self-assembled monolayers (SAMs) combining a Y-shaped aromatic carboxylic acid (1,3,5-benzenetribenzoic acid, H3BTB) and a cage-type alicyclic carboxylic acid (adamantane carboxylic acid, AdCA) were investigated by scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and near edge X-ray absorption fine structure (NEXAFS) spectroscopy. The SAMs, prepared by molecular adsorption from solution on Au substrates modified by underpotential deposition of Ag, exhibit a pronounced dependence of their structure on the assembly protocol. Exposing an H3BTB SAM to AdCA, the highly regular row structure of the native H3BTB layer persists and STM imaging does not show signs of AdCA adsorption. This is in striking contrast to the disordered arrangements of H3BTB and the presence of AdCA employing the inverted adsorption sequence or coadsorption of the two molecules. However, spectroscopic analysis of the H3BTB SAM exposed to AdCA reveals the presence also of the latter, suggesting that the AdCA molecules are hidden in the nanotunnels of the H3BTB monolayer. Direct evidence for the intercalation of AdCA is obtained by STM manipulation experiments which lay bare areas of AdCA molecules upon local removal of H3BTB. Surprisingly, these are densely packed and arranged into a highly ordered monolayer. Formation of such a compact AdCA layer is explained by expulsion of AdCA from the H3BTB nanotunnels of the surrounding intact mixed SAM, driven by release of stress in the nanotunnels built up when AdCA is intercalated.PostprintPeer reviewe

    Polyclonal epitope mapping reveals temporal dynamics and diversity of human antibody responses to H5N1 vaccination

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    Novel influenza A virus (IAV) strains elicit recall immune responses to conserved epitopes, making them favorable antigenic choices for universal influenza virus vaccines. Evaluating these immunogens requires a thorough understanding of the antigenic sites targeted by the polyclonal antibody (pAb) response, which single-particle electron microscopy (EM) can sensitively detect. In this study, we employ EM polyclonal epitope mapping (EMPEM) to extensively characterize the pAb response to hemagglutinin (HA) after H5N1 immunization in humans. Cross-reactive pAbs originating from memory B cells immediately bound the stem of HA and persisted for more than a year after vaccination. In contrast, de novo pAb responses to multiple sites on the head of HA, targeting previously determined key neutralizing sites on H5 HA, expanded after the second immunization and waned quickly. Thus, EMPEM provides a robust tool for comprehensively tracking the specificity and durability of immune responses elicited by novel universal influenza vaccine candidates

    European Paediatric Formulation Initiative (EuPFI)-Formulating Ideas for Better Medicines for Children.

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    Ā© American Association of Pharmaceutical Scientists 2016, published by Springer US, available online at doi: https://doi.org/10.1208/s12249-016-0584-1The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.Peer reviewedFinal Accepted Versio
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