577 research outputs found

    Patient and clinician factors associated with prehospital pain treatment and outcomes: cross sectional study

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    Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.Objective: We aimed to identify how patient (age, sex, condition) and paramedic factors (sex, role) affected prehospital analgesic administration and pain alleviation. Methods: We used a cross-sectional design with a 7-day retrospective sample of adults aged 18 years or over requiring primary emergency transport to hospital, excluding patients with Glasgow Coma Scale below 13, in two UK ambulance services. Multivariate multilevel regression using Stata 14 analysed factors independently associated with analgesic administration and a clinically meaningful reduction in pain (≥2 points on 0–10 numerical verbal pain score [NVPS]). Results: We included data on 9574 patients. At least two pain scores were recorded in 4773 (49.9%) patients. For all models fitted there was no significant relationship between analgesic administration or pain reduction and sex of the patient or ambulance staff. Reduction in pain (NVPS ≥2) was associated with ambulance crews including at least one paramedic (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.14 to 2.04, p < 0.01), with any recorded pain score and suspected cardiac pain (OR 2.2, 95% CI 1.02 to 4.75). Intravenous morphine administration was also more likely where crews included a paramedic (OR 2.82, 95% CI 1.93 to 4.13, P < 0.01), attending patients aged 51 to 64 years (OR 2.04, 95% CI 1.21 to 3.45, p = 0.01), in moderate to severe (NVPS 4–10) compared with lower levels of pain for any clinical condition group compared with the reference condition. Conclusion: There was no association between patient sex or ambulance staff sex or grade and analgesic administration or pain reduction.Peer reviewedFinal Accepted Versio

    Repo-Man/protein phosphatase 1 SUMOylation mediates binding to lamin A and serine 22 dephosphorylation

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    © 2022 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License. http://creativecommons.org/licenses/by/4.0/Lamin A phosphorylation/de-phosphorylation is an important process during cells division as it allows for nuclear envelope (NE) disassembly at mitotic entry and its re-assembly during mitotic exit. Several kinases have been identified as responsible for these phosphorylations, but no protein phosphatase has been implicated in their reversal. One of the mitotic phosphosites in lamin A responsible for its dynamic behaviour is serine 22 (S22) which is de-phosphorylated during mitotic exit. Recent evidence has also linked the nuclear pool of lamin A S22ph in interphase to gene expression regulation. Previous work suggested that the phosphatase responsible for lamin A S22 de-phosphorylation is chromatin bound and interacts with lamin A via SUMO-SIM motives. We have previously reported that Repo-Man/protein phosphatase 1 (PP1) is a chromatin-associated phosphatase that regulates NE reformation. Here we propose that Repo-Man/PP1 phosphatase mediates lamin A S22 de-phosphorylation. We indeed show that depletion of Repo-Man leads to NE defects, causes hyperphosphorylation of lamin A S22 that can be rescued by a wild-type but not a SUMOylation-deficient mutant. Lamin A and Repo-Man interact in vivo and in vitro, and the interaction is mediated by SUMOylation. Moreover, the localization of Repo-Man/PP1 to the chromatin is essential for lamin A S22 de-phosphorylation.Peer reviewedFinal Published versio

    The Nakuru eye disease cohort study: methodology & rationale.

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    BACKGROUND: No longitudinal data from population-based studies of eye disease in sub-Saharan-Africa are available. A population-based survey was undertaken in 2007/08 to estimate the prevalence and determinants of blindness and low vision in Nakuru district, Kenya. This survey formed the baseline to a six-year prospective cohort study to estimate the incidence and progression of eye disease in this population. METHODS/DESIGN: A nationally representative sample of persons aged 50 years and above were selected between January 2007 and November 2008 through probability proportionate to size sampling of clusters, with sampling of individuals within clusters through compact segment sampling. Selected participants underwent detailed ophthalmic examinations which included: visual acuity, autorefraction, visual fields, slit lamp assessment of the anterior and posterior segments, lens grading and fundus photography. In addition, anthropometric measures were taken and risk factors were assessed through structured interviews. Six years later (2013/2014) all subjects were invited for follow-up assessment, repeating the baseline examination methodology. DISCUSSION: The methodology will provide estimates of the progression of eye diseases and incidence of blindness, visual impairment, and eye diseases in an adult Kenyan population

    The COMPLETE Survey of Star-Forming Regions: Phase I Data

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    We present an overview of data available for the Ophiuchus and Perseus molecular clouds from ``Phase I'' of the COMPLETE Survey of Star-Forming Regions. This survey provides a range of data complementary to the Spitzer Legacy Program ``From Molecular Cores to Planet Forming Disks.'' Phase I includes: Extinction maps derived from 2MASS near-infrared data using the NICER algorithm; extinction and temperature maps derived from IRAS 60 and 100um emission; HI maps of atomic gas; 12CO and 13CO maps of molecular gas; and submillimetre continuum images of emission from dust in dense cores. Not unexpectedly, the morphology of the regions appears quite different depending on the column-density tracer which is used, with IRAS tracing mainly warmer dust and CO being biased by chemical, excitation and optical depth effects. Histograms of column-density distribution are presented, showing that extinction as derived from 2MASS/NICER gives the closest match to a log-normal distribution as is predicted by numerical simulations. All the data presented in this paper, and links to more detailed publications on their implications are publically available at the COMPLETE website.Comment: Accepted by AJ. Full resolution version available from: http://www.cfa.harvard.edu/COMPLETE/papers/complete_phase1.pd

    Six-Year Incidence of Blindness and Visual Impairment in Kenya: The Nakuru Eye Disease Cohort Study.

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    PURPOSE: To describe the cumulative 6-year incidence of visual impairment (VI) and blindness in an adult Kenyan population. The Nakuru Posterior Segment Eye Disease Study is a population-based sample of 4414 participants aged ?50 years, enrolled in 2007-2008. Of these, 2170 (50%) were reexamined in 2013-2014. METHODS: The World Health Organization (WHO) and US definitions were used to calculate presenting visual acuity classifications based on logMAR visual acuity tests at baseline and follow-up. Detailed ophthalmic and anthropometric examinations as well as a questionnaire, which included past medical and ophthalmic history, were used to assess risk factors for study participation and vision loss. Cumulative incidence of VI and blindness, and factors associated with these outcomes, were estimated. Inverse probability weighting was used to adjust for nonparticipation. RESULTS: Visual acuity measurements were available for 2164 (99.7%) participants. Using WHO definitions, the 6-year cumulative incidence of VI was 11.9% (95%CI [confidence interval]: 10.3-13.8%) and blindness was 1.51% (95%CI: 1.0-2.2%); using the US classification, the cumulative incidence of blindness was 2.70% (95%CI: 1.8-3.2%). Incidence of VI increased strongly with older age, and independently with being diabetic. There are an estimated 21 new cases of VI per year in people aged ?50 years per 1000 people, of whom 3 are blind. Therefore in Kenya we estimate that there are 92,000 new cases of VI in people aged ?50 years per year, of whom 11,600 are blind, out of a total population of approximately 4.3 million people aged 50 and above. CONCLUSIONS: The incidence of VI and blindness in this older Kenyan population was considerably higher than in comparable studies worldwide. A continued effort to strengthen the eye health system is necessary to support the growing unmet need in an aging and growing population

    The incidence of diabetes mellitus and diabetic retinopathy in a population-based cohort study of people age 50 years and over in Nakuru, Kenya.

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    BACKGROUND: The epidemic rise of diabetes carries major negative public health and economic consequences particularly for low and middle-income countries. The highest predicted percentage growth in diabetes is in the sub-Saharan Africa (SSA) region where to date there has been no data on the incidence of diabetic retinopathy from population-based cohort studies and minimal data on incident diabetes. The primary aims of this study were to estimate the cumulative six-year incidence of Diabetes Mellitus (DM) and DR (Diabetic Retinopathy), respectively, among people aged ≥50 years in Kenya. METHODS: Random cluster sampling with probability proportionate to size were used to select a representative cross-sectional sample of adults aged ≥50 years in 2007-8 in Nakuru District, Kenya. A six-year follow-up was undertaken in 2013-14. On both occasions a comprehensive ophthalmic examination was performed including LogMAR visual acuity, digital retinal photography and independent grading of images. Data were collected on general health and risk factors. The primary outcomes were the incidence of diabetes mellitus and the incidence of diabetic retinopathy, which were calculated by dividing the number of events identified at 6-year follow-up by the number of people at risk at the beginning of follow-up. Age-adjusted risk ratios of the outcomes (DM and DR respectively) were estimated for each covariate using a Poisson regression model with robust error variance to allow for the clustered design and including inverse-probability weighting. RESULTS: At baseline, 4414 participants aged ≥50 years underwent complete examination. Of the 4104 non-diabetic participants, 2059 were followed-up at six-years (50 · 2%). The cumulative incidence of DM was estimated at 61 · 0 per 1000 (95% CI: 50 · 3-73 · 7) in people aged ≥50 years. The cumulative incidence of DR in the sample population was estimated at 15 · 8 per 1000 (95% CI: 9 · 5-26 · 3) among those without DM at baseline, and 224 · 7 per 1000 (116.9-388.2) among participants with known DM at baseline. A multivariable risk factor analysis demonstrated increasing age and higher body mass index to be associated with incident DM. DR incidence was strongly associated with increasing age, and with higher BMI, urban dwelling and higher socioeconomic status. CONCLUSIONS: Diabetes Mellitus is a growing public health concern with a major complication of diabetic retinopathy. In a population of 1 · 6 million, of whom 150,000 are ≥50 years, we estimated that 1650 people aged ≥50 develop DM per year, and 450 develop DR. Strengthening of health systems is necessary to reduce incident diabetes and its complications in this and similar settings

    Implementation of an electronic monitoring and evaluation system for the antiretroviral treatment programme in the Cape Winelands district, South Africa: a qualitative evaluation

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    BACKGROUND: A pragmatic three-tiered approach to monitor the world's largest antiretroviral treatment (ART) programme was adopted by the South African National Department of Health in 2010. With the rapid expansion of the programme, the limitations of the paper-based register (tier 1) were the catalyst for implementation of the stand-alone electronic register (tier 2), which offers simple digitisation of the paper-based register. This article engages with theory on implementation to identify and contextualise enabling and constraining factors for implementation of the electronic register, to describe experiences and use of the register, and to make recommendations for implementation in similar settings where standardisation of ART monitoring and evaluation has not been achieved. METHODS: We conducted a qualitative evaluation of the roll-out of the register. This comprised twenty in-depth interviews with a diverse sample of stakeholders at facility, sub-district, and district levels of the health system. Facility-level participants were selected across five sub-districts, including one facility per sub-district. Responses were coded and analysed using a thematic approach. An implementation science framework guided interpretation of the data. Results & DISCUSSION: We identified the following seven themes: 1) ease of implementation, 2) perceived value of an electronic M&E system, 3) importance of stakeholder engagement, 4) influence of a data champion, 5) operational and logistical factors, 6) workload and role clarity, and 7) importance of integrating the electronic register with routine facility monitoring and evaluation. Interpreting our findings through an implementation theory enabled us to construct the scaffolding for implementation across the five facility-settings. This approach illustrated that implementation was not a linear process but occurred at two nodes: at the adoption of the register for roll-out, and at implementation at facility-level. CONCLUSION: In this study we found that relative advantage of an intervention and stakeholder engagement are critical to implementation. We suggest that without these aspects of implementation, formative and summative outcomes of implementation at both the adoption and coalface stages of implementation would be negatively affected

    Interphase chromosome positioning in in vitro porcine cells and ex vivo porcine tissues

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    Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.BACKGROUND: In interphase nuclei of a wide range of species chromosomes are organised into their own specific locations termed territories. These chromosome territories are non-randomly positioned in nuclei which is believed to be related to a spatial aspect of regulatory control over gene expression. In this study we have adopted the pig as a model in which to study interphase chromosome positioning and follows on from other studies from our group of using pig cells and tissues to study interphase genome re-positioning during differentiation. The pig is an important model organism both economically and as a closely related species to study human disease models. This is why great efforts have been made to accomplish the full genome sequence in the last decade. RESULTS: This study has positioned most of the porcine chromosomes in in vitro cultured adult and embryonic fibroblasts, early passage stromal derived mesenchymal stem cells and lymphocytes. The study is further expanded to position four chromosomes in ex vivo tissue derived from pig kidney, lung and brain. CONCLUSIONS: It was concluded that porcine chromosomes are also non-randomly positioned within interphase nuclei with few major differences in chromosome position in interphase nuclei between different cell and tissue types. There were also no differences between preferred nuclear location of chromosomes in in vitro cultured cells as compared to cells in tissue sections. Using a number of analyses to ascertain by what criteria porcine chromosomes were positioned in interphase nuclei; we found a correlation with DNA content.This study is partly supported by Sygen International PLC

    Dental and craniofacial defects in the Crtap−/− mouse model of osteogenesis imperfecta type VII

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    BackgroundInactivating mutations in the gene for cartilage‐associated protein (CRTAP) cause osteogenesis imperfecta type VII in humans, with a phenotype that can include craniofacial defects. Dental and craniofacial manifestations have not been a focus of case reports to date. We analyzed the craniofacial and dental phenotype of Crtap−/− mice by skull measurements, micro‐computed tomography (micro‐CT), histology, and immunohistochemistry.ResultsCrtap−/− mice exhibited a brachycephalic skull shape with fusion of the nasofrontal suture and facial bones, resulting in mid‐face retrusion and a class III dental malocclusion. Loss of CRTAP also resulted in decreased dentin volume and decreased cellular cementum volume, though acellular cementum thickness was increased. Periodontal dysfunction was revealed by decreased alveolar bone volume and mineral density, increased periodontal ligament (PDL) space, ectopic calcification within the PDL, bone‐tooth ankylosis, altered immunostaining of extracellular matrix proteins in bone and PDL, increased pSMAD5, and more numerous osteoclasts on alveolar bone surfaces.ConclusionsCrtap−/− mice serve as a useful model of the dental and craniofacial abnormalities seen in individuals with osteogenesis imperfecta type VII.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155878/1/dvdy166.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155878/2/dvdy166_am.pd
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