712 research outputs found

    Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study

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    INTRODUCTION: Type 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research. METHODS AND ANALYSIS: Using the National Institute for Health Research Clinical Research Network, patients >5 years of age diagnosed clinically with type 1 diabetes (and their siblings) are recruited within 6 months of diagnosis. Participants agree to have their clinical, laboratory and demographic data stored on a secure database, for their clinical progress to be monitored using information held by NHS Digital, and to be contacted about additional research, in particular immunotherapy and other interventions. An optional blood sample is taken for islet autoantibody measurement and storage of blood and DNA for future analyses. Data will be analysed statistically to describe the presentation of incident type 1 diabetes in a contemporary UK population. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent NHS Research Ethics Service. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals.This work was supported by Diabetes UK grant number 09/0003919 and the Juvenile Diabetes Research Foundation grant number 9-2010-407. Recruitment is supported by staff at the National Institute for Health Research Clinical Research Network

    Mediation Analysis of High Blood Pressure Targets, Arrhythmias, and Shock Mortality

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    In vivo editing of the pan-endothelium by immunity evading simian adenoviral vector

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    Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought to limit the potential of off-target editing. To this end, we have exploited the molecular promiscuities of adenovirus (Ad) to address the key requirements of CRISPR/Cas9-facilitated gene therapy. In this regard, we have endeavored capsid engineering of a simian (chimpanzee) adenovirus isolate 36 (SAd36) to achieve targeted modifications of vector tropism. The SAd36 vector with the myeloid cell-binding peptide (MBP) incorporated in the capsid has allowed selective in vivo modifications of the vascular endothelium. Importantly, vascular endothelium can serve as an effective non-hepatic cellular source of deficient serum factors relevant to several inherited genetic disorders. In addition to allowing for re-directed tropism, capsid engineering of nonhuman primate Ads provide the means to circumvent pre-formed vector immunity. Herein we have generated a SAd36. MBP vector that can serve as a single intravenously administered agent allowing effective and selective in vivo editing for endothelial target cells of the mouse spleen, brain and kidney. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request

    Epidemiology of ventilator-associated pneumonia in a long-term acute care hospital

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    objective. To characterize the epidemiology and microbiology of ventilator-associated pneumonia (VAP) in a long-term acute care hospital (LTACH). design. Retrospective study of prospectively identified cases of VAP. setting. Single-center, 207-bed LTACH with the capacity to house 42 patients requiring mechanical ventilation, evaluated from April 1, 2006, through January 31, 2008 methods. Data on the occurrence of VAP were collected prospectively as part of routine infection surveillance at Radius Specialty Hospital. After March 2006, Radius Specialty Hospital implemented a bundle of interventions for the prevention of VAP (hereafter referred to as the VAP-bundle approach). A case of VAP was defined as a patient who required mechanical ventilation at Radius Specialty Hospital for at least 48 hours before any symptoms of pneumonia appeared and who met the Centers for Disease Control and Prevention criteria for VAP. Sputum samples were collected from a tracheal aspirate if there was clinical suspicion of VAP, and these samples were semiquantitatively cultured. results. During the 22-month study period, 23 cases of VAP involving 19 patients were associated with 157 LTACH admissions (infection rate, 14.6%), corresponding to a rate of 1.67 cases per 1,000 ventilator-days, which is a 56% reduction from the VAP rate of 3.8 cases per 1,000 ventilator-days reported before the implementation of the VAP-bundle approach ( ). Microbiological data were available for P ! .001 21 (91%) of 23 cases of VAP. Cases of VAP in the LTACH were frequently polymicrobial (mean number ‫ע‬ SD, pathogens per 1.78 ‫ע‬ 1.0 case of VAP), and 20 (95%) of 21 cases of VAP had at least 1 pathogen (Pseudomonas species, Acinetobacter species, gram-negative bacilli resistant to more than 3 antibiotics, or methicillin-resistant Staphylococcus aureus) cultured from a sputum sample. LTACH patients with VAP were more likely to have a neurological reason for ventilator dependence, compared with LTACH patients without VAP (69.6% of cases of VAP vs 39% of cases of respiratory failure; ). In addition, patients with VAP had a longer length of LTACH stay, compared P p .014 with patients without VAP (median length of stay, 131 days vs 39 days; ). In 6 (26%) of 23 cases of VAP, the patient was eventually P p .002 weaned from use of mechanical ventilation. Of the 19 patients with VAP, 1 (5%) did not survive the LTACH stay. conclusions. The VAP rate in the LTACH is lower than the VAP rate reported in acute care hospitals. Cases of VAP in the LTACH were frequently polymicrobial and were associated with multidrug-resistant pathogens and increased length of stay. The guidelines from the Centers for Disease Control and Prevention that are aimed at reducing cases of VAP appear to be effective if applied in the LTACH setting. Ventilator-associated pneumonia (VAP) is the second most common nosocomial infection in the critical care setting. Infect Control Hosp Epidemiol 1 It is associated with increased morbidity and increased use of healthcare resources. 2 The epidemiology of VAP in intensive care units (ICUs) of acute care hospitals has been widely characterized

    Complete nucleotide sequences and genome organization of a cherry isolate of cherry leaf roll virus

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    The complete nucleotide sequence of cherry leaf roll virus (CLRV, genus Nepovirus) from a naturally infected cherry tree (Prunus avium cv. Bing) in North America was determined. RNA1 and RNA2 consist of 7,893 and 6,492 nucleotides, respectively, plus a poly-(A) tail. Each RNA encodes a single potential open reading frame. The first 657 nucleotides of RNA1 and RNA2 are 99% identical and include the 5′-UTR and the first 214 deduced amino acids of the polyproteins following the first of two in-frame start codons. Phylogenetic analysis reveals close relationships between CLRV and members of subgroup C of the genus Nepovirus

    Epidemiology of ventilator-associated pneumonia in a long-term acute care hospital

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    JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaborating with JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology

    Promoting the achievement in schools of children and young people in care

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    As of March 2017, there were 72,670 children and young people in care in England. The number of looked after children has continued to increase steadily over the last eight years. Sixty per cent of these children are in care because of abuse or neglect and three-quarters are placed in foster care arrangements. Children and young people who are in or have experienced care remain one of the lowest performing groups in terms of educational outcomes. The average Attainment 8 score for children in care is 19.3 compared to 44.5 for non-looked after children and 19.3 for children in need. In 2017 there was an increase in the percentage of children in care achieving a pass in English and Mathematics from 17.4% to 17.5% and also in entering EBacc. Care leavers can experience poorer employment and health outcomes after leaving school compared to their peers. They are over-represented amongst the offender population and those who experience homelessness. However, research is emerging to show that children and young people in care can have very positive experiences of school if they are supported effectively to reach their full potential academically and socially. The purpose of this report is to share practice in local authorities (LA) from across England and Wales that is contributing to improved outcomes and school experiences for children and young people in care. The case studies were all undertaken as part of the Promoting the Achievement of Looked after Children (PALAC) programme between 2014 and 2017. This report presents an account of the programme, including the activities undertaken by the participants and the outcomes of the programme to date for pupils in care and staff in the participating virtual schools (VS) and local authorities
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