98 research outputs found

    A DevOps Capability - The IVI DevOps Effectiveness Assessment

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    The DevOps Effectiveness Assessment (DEA) is a new IVI assessment drawing on the IT Capability Maturity Framework (IT-CMF). The assessment provides a holistic analysis of an organization’s DevOps maturity, and identifies the key relevant IT-CMF Critical Capabilities (CCs) to aid improvement. DevOps refers to a set of technical, architectural, and cultural practices aimed at increasing the efficiency and effectiveness of delivering business needs into production, through improved communication and collaboration between business, development, and IT operations. The DEA is based on rigorous academic research and collaboration with experts from leading organizations. This paper outlines the key insights from this research, which have informed the development of the DEA

    Targeting Astrocytes Ameliorates Neurologic Changes in a Mouse Model of Alzheimer\u27s Disease

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    Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer\u27s disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically activated phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes in APP/PS1 mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes with the immune/inflammatory calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway, shown by our laboratory and others to orchestrate biochemical cascades leading to astrocyte activation. After several months of treatment with Gfa2-VIVIT, APP/PS1 mice exhibited improved cognitive and synaptic function, reduced glial activation, and lower amyloid levels. The results confirm a deleterious role for activated astrocytes in AD and lay the groundwork for exploration of other novel astrocyte-based therapies

    Exploring the Production and Utilisation of Pre-sentence Reports (PSRs) in the Youth Justice System

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    Ipsos and Manchester Metropolitan University (MMU) were commissioned by the Youth Justice Board (YJB) to conduct research into Pre-Sentence Reports (PSRs). PSRs bring together important information about the child to help inform the court’s sentencing decision. The research was exploratory and the primary research objectives were to: Understand commonalities and differences in PSR reports associated with custodial or community outcomes for Black children compared with White children; and Develop learning around the processes and decision-making involved in producing and utilising PSRs in these cases, including the perceived purpose of PSRs. This work builds on previous research which showed that Black children were more likely to receive harsher sentencing outcome after controlling for other factor

    Advice for journalists covering Covid-19: Welsh NHS confederation

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    The outbreak of COVID-19 is placing an unprecedented strain on health services in Wales and across the world. At the same time, coverage of the outbreak is essential, and there is a great demand from media organisations and their audiences to receive information about the outbreak and its frontline. This can put additional pressures on health care organisations and staff and may in certain cases interfere with their operations in dealing with the outbreak. This document has been prepared by Professor Karin Wahl-Jorgensen, Cardiff University, to support the work of the Welsh NHS Confederation. It draws on input from leading academics, journalists and PR practitioners (full list of contributors on p. 9). The document provides a number of suggestions for media organisations designed to facilitate coverage in and around healthcare facilities in Wales. The experts involved in preparing this document are independent from the NHS, and the document does not reflect official NHS policy. Here is a summary of our advice: 1. Responsible, detailed, and accurate reporting of COVID-19 is an essential public service. 2. Use credible experts as sources and be wary of unverified rumour 3. News organisations should use pooled materials whenever possible. 4. If looking for information verification, check other sources first before contacting NHS. 5. Ensure compliance with procedures for risk assessment and consent. 6. Enforce social distancing and ensure safe use of equipment. 7. Ensure risk assessments have been carried out prior to hospital visits and face-toface interactions with NHS staff. 8. Obtain consent from anyone interviewed or filmed. 9. When making requests for interviews or information, be specific about who you need to speak to, and where, what and how the information will be used

    Calcineurin/NFAT Signaling in Activated Astrocytes Drives Network Hyperexcitability in A\u3cem\u3eβ\u3c/em\u3e-Bearing Mice

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    Hyperexcitable neuronal networks are mechanistically linked to the pathologic and clinical features of Alzheimer\u27s disease (AD). Astrocytes are a primary defense against hyperexcitability, but their functional phenotype during AD is poorly understood. Here, we found that activated astrocytes in the 5xFAD mouse model were strongly associated with proteolysis of the protein phosphatase calcineurin (CN) and the elevated expression of the CN-dependent transcription factor nuclear factor of activated T cells 4 (NFAT4). Intrahippocampal injections of adeno-associated virus vectors containing the astrocyte-specific promoter Gfa2 and the NFAT inhibitory peptide VIVIT reduced signs of glutamate-mediated hyperexcitability in 5xFAD mice, measured in vivo with microelectrode arrays and ex vivo brain slices, using whole-cell voltage clamp. VIVIT treatment in 5xFAD mice led to increased expression of the astrocytic glutamate transporter GLT-1 and to attenuated changes in dendrite morphology, synaptic strength, and NMDAR-dependent responses. The results reveal astrocytic CN/NFAT4 as a key pathologic mechanism for driving glutamate dysregulation and neuronal hyperactivity during AD

    The BpTRU automatic blood pressure monitor compared to 24 hour ambulatory blood pressure monitoring in the assessment of blood pressure in patients with hypertension

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    BACKGROUND: Increasing evidence suggests that ABPM more closely predicts target organ damage than does clinic measurement. Future guidelines may suggest ABPM as routine in the diagnosis and monitoring of hypertension. This would create difficulties as this test is expensive and often difficult to obtain. The purpose of this study is to determine the degree to which the BpTRU automatic blood pressure monitor predicts results on 24 hour ambulatory blood pressure monitoring (ABPM). METHODS: A quantitative analysis comparing blood pressure measured by the BpTRU device with the mean daytime blood pressure on 24 hour ABPM. The study was conducted by the Centre for Studies in Primary Care, Queen's University, Kingston, Ontario, Canada on adult primary care patients who are enrolled in two randomized controlled trials on hypertension. The main outcomes were the mean of the blood pressures measured at the three most recent office visits, the initial measurement on the BpTRU-100, the mean of the five measurements on the BpTRU monitor, and the daytime average on 24 hour ABPM. RESULTS: The group mean of the three charted clinic measured blood pressures (150.8 (SD10.26) / 82.9 (SD 8.44)) was not statistically different from the group mean of the initial reading on BpTRU (150.0 (SD21.33) / 83.3 (SD12.00)). The group mean of the average of five BpTRU readings (140.0 (SD17.71) / 79.8 (SD 10.46)) was not statistically different from the 24 hour daytime mean on ABPM (141.5 (SD 13.25) / 79.7 (SD 7.79)). Within patients, BpTRU average correlated significantly better with daytime ambulatory pressure than did clinic averages (BpTRU r = 0.571, clinic r = 0.145). Based on assessment of sensitivity and specificity at different cut-points, it is suggested that the initial treatment target using the BpTRU be set at <135/85 mmHG, but achievement of target should be confirmed using 24 hour ABPM. CONCLUSION: The BpTRU average better predicts ABPM than does the average of the blood pressures recorded on the patient chart from the three most recent visits. The BpTRU automatic clinic blood pressure monitor should be used as an adjunct to ABPM to effectively diagnose and monitor hypertension

    Costs and Consequences: Hepatitis C Seroprevalence in the Military and Its Impact on Potential Screening Strategies

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    UNLABELLED: Knowledge of the contemporary epidemiology of hepatitis C viral (HCV) infection among military personnel can inform potential Department of Defense screening policy. HCV infection status at the time of accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period 2007-2010. A cost model was developed from the perspective of the Department of Defense for a military applicant screening program. Return on investment was based on comparison between screening program costs and potential treatment costs avoided. The prevalence of HCV antibody-positive and chronic HCV infection at accession among younger recently deployed military personnel born after 1965 was 0.98/1000 (95% confidence interval 0.45-1.85) and 0.43/1000 (95% confidence interval 0.12-1.11), respectively. Among these, service-related incidence was low; 64% of infections were present at the time of accession. With no screening, the cost to the Department of Defense of treating the estimated 93 cases of chronic HCV cases from a single year\u27s accession cohort was 9.3million.ScreeningwiththeHCVantibodytestfollowedbythenucleicacidtestforconfirmationyieldedanetannualsavingsanda9.3 million. Screening with the HCV antibody test followed by the nucleic acid test for confirmation yielded a net annual savings and a 3.1 million dollar advantage over not screening. CONCLUSIONS: Applicant screening will reduce chronic HCV infection in the force, result in a small system costs savings, and decrease the threat of transfusion-transmitted HCV infection in the battlefield blood supply and may lead to earlier diagnosis and linkage to care; initiation of an applicant screening program will require ongoing evaluation that considers changes in the treatment cost and practice landscape, screening options, and the epidemiology of HCV in the applicant/accession and overall force populations

    Hepatitis B Seroprevalence in the U.S. Military and its Impact on Potential Screening Strategies

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    INTRODUCTION: Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. MATERIALS AND METHODS: HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. RESULTS: The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. CONCLUSIONS: Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice

    Advice for journalists covering Covid-19: Welsh NHS confederation

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    The outbreak of COVID-19 is placing an unprecedented strain on health services in Wales and across the world. At the same time, coverage of the outbreak is essential, and there is a great demand from media organisations and their audiences to receive information about the outbreak and its frontline. This can put additional pressures on health care organisations and staff and may in certain cases interfere with their operations in dealing with the outbreak. This document has been prepared by Professor Karin Wahl-Jorgensen, Cardiff University, to support the work of the Welsh NHS Confederation. It draws on input from leading academics, journalists and PR practitioners (full list of contributors on p. 9). The document provides a number of suggestions for media organisations designed to facilitate coverage in and around healthcare facilities in Wales. The experts involved in preparing this document are independent from the NHS, and the document does not reflect official NHS policy. Here is a summary of our advice: 1. Responsible, detailed, and accurate reporting of COVID-19 is an essential public service. 2. Use credible experts as sources and be wary of unverified rumour 3. News organisations should use pooled materials whenever possible. 4. If looking for information verification, check other sources first before contacting NHS. 5. Ensure compliance with procedures for risk assessment and consent. 6. Enforce social distancing and ensure safe use of equipment. 7. Ensure risk assessments have been carried out prior to hospital visits and face-toface interactions with NHS staff. 8. Obtain consent from anyone interviewed or filmed. 9. When making requests for interviews or information, be specific about who you need to speak to, and where, what and how the information will be used

    Differential Expression of Iron Acquisition Genes by Brucella melitensis and Brucella canis during Macrophage Infection

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    Brucella spp. cause chronic zoonotic disease often affecting individuals and animals in impoverished economic or public health conditions; however, these bacteria do not have obvious virulence factors. Restriction of iron availability to pathogens is an effective strategy of host defense. For brucellae, virulence depends on the ability to survive and replicate within the host cell where iron is an essential nutrient for the growth and survival of both mammalian and bacterial cells. Iron is a particularly scarce nutrient for bacteria with an intracellular lifestyle. Brucella melitensis and Brucella canis share ∼99% of their genomes but differ in intracellular lifestyles. To identify differences, gene transcription of these two pathogens was examined during infection of murine macrophages and compared to broth grown bacteria. Transcriptome analysis of B. melitensis and B. canis revealed differences of genes involved in iron transport. Gene transcription of the TonB, enterobactin, and ferric anguibactin transport systems was increased in B. canis but not B. melitensis during infection of macrophages. The data suggest differences in iron requirements that may contribute to differences observed in the lifestyles of these closely related pathogens. The initial importance of iron for B. canis but not for B. melitensis helps elucidate differing intracellular survival strategies for two closely related bacteria and provides insight for controlling these pathogens
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