Recommendation report for the implementation of research data management policy and for a sustainable research data management service at the University of Exeter

This is the Open Access and Research Data Management Policy Task and Finish Group's recommendation report for the implementation of research data management policy and a sustainable research data management service at the University of Exeter.JIS

Building PRM in sub-Saharan Africa

It is estimated that about 50% of people in low- and middle- income countries who require rehabilitation do not get it. Multidisciplinary rehabilitation services led by Physical and Rehabilitation Medicine (PRM) physicians have been shown to improve functioning, independence and the quality of life of persons with reduced functioning or disability. However, there is a dearth of PRM physicians in low to middle income countries (LMICs), particularly in sub-Saharan Africa. One potential solution to this lack of specialists is the establishment of PRM training programs, which are currently lacking. The International Rehabilitation Forum (IRF) developed and implemented a fellowship program to train physicians in rehabilitation medicine and has been successful in Ghana, Ethiopia and Cameroon, all LMICs in sub-Saharan Africa. However, ongoing challenges include inadequate PRM trainers, availability of logistics and services for hands on experience, and funding. The fellowship program has a promising future and an ultimate goal of having locally trained fellows leading the program and expanding it to other LMICs. There has however been no publication of the process followed to achieve this or of a similar process undertaken anywhere in Africa. The process followed in this publication highlights the journey from engaging stakeholders to the admission of new and current fellows in training

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Legionella pneumophila occurrence in reduced-occupancy buildings in 11 cities during the COVID-19 pandemic

ABSTRACT: In spring 2020, numerous buildings were closed or operated at reduced occupancies to slow the spread of COVID-19. An unintended consequence of these social distancing measures was a reduction in water demand in many buildings. Concerns arose that contaminants associated with water stagnation, such as Legionella pneumophila, could become prevalent. To investigate the potential public health risk associated with L. pneumophila, samples from 26 reduced-occupancy buildings in 11 cities in the United States, Canada, and Switzerland were analyzed for L. pneumophila using liquid culture (Legiolert, n = 258) and DNA-based methods (qPCR/ddPCR, n = 138). L. pneumophila culture-positivity was largely associated with five buildings, each of which had specific design or operational deficiencies commonly associated with L. pneumophila occurrence. Samples from buildings with free chlorine residual disinfection had higher culture-positivity (37%) than samples from buildings with chloramine (1%). Additionally, 78% of culture-positive samples occurred when the disinfectant residual was ≤0.1 mg L−1 Cl2 and only three free chlorine samples were culture-positive when the disinfectant residual was >0.2 mg L−1 as Cl2. Although overall sample positivity using culture- and DNA-based methods was equivalent (34% vs. 35%), there was disagreement between the methods in 13% of samples (n = 18 of 138). Few buildings reported any water management activities, and L. pneumophila concentrations in flushed samples were occasionally greater than in first-draw samples. This study provides insight into how building plumbing characteristics and water management practices contribute to L. pneumophila occurrence during low water use periods and can inform targeted prevention and mitigation efforts

Endosperm development : dynamic processes and cellular innovations underlying sibling altruism

The endosperm is a product of fertilization that evolved to support and nourish its genetic twin sibling embryo. Cereal endosperm accumulates starch and protein stores, which later support the germinating seedling. These nutritional stores prompted the domestication of cereals and are the focus of ongoing efforts for crop improvement and biotechnological innovations. Endosperm development entails several novel modifications to basic cellular and developmental processes. Cereals display nuclear endosperm development, which begins with a period of free nuclear division to generate a coenocyte. Cytoskeletal arrays distribute nuclei around the periphery of the cytoplasm and direct the subsequent deposition of cell wall material during cellularization. Positional cues and signaling systems function dynamically in the specification of the four major cell types: transfer cells, embryo-surrounding cells, starchy endosperm (SE), and aleurone. Genome balance, epigenetic gene regulation, and parent-of-origin effects are essential for directing these processes. Transfer cells transport solutes, including sugars and amino acids, from the maternal plant tissues into the developing grain where they are partitioned between embryo and SE cells. Cells of the embryo-surrounding region appear to coordinate development of the embryo and endosperm. As the seed matures, SE cells assimilate starch and protein stores, undergo DNA endoreduplication, and finally undergo programmed cell death. In contrast, aleurone cells follow a maturation program similar to the embryo, allowing them to survive desiccation. At germination, the aleurone cells secrete amylases and proteases that hydrolyze the storage products of the SE to nourish the germinating seedlin