Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.

BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer

Supporting Remote Survey Data Analysis by Co-researchers with Learning Disabilities through Inclusive and Creative Practices and Data Science Approaches

Through a process of robust co-design, we created a bespoke accessible survey platform to explore the role of co-researchers with learning disabilities (LDs) in research design and analysis. A team of co-researchers used this system to create an online survey to challenge public understanding of LDs [3]. Here, we describe and evaluate the process of remotely co-analyzing the survey data across 30 meetings in a research team consisting of academics and nonacademics with diverse abilities amid new COVID-19 lockdown challenges. Based on survey data with >1,500 responses, we first coanalyzed demographics using graphs and art & design approaches. Next, co-researchers co-analyzed the output of machine learningbased structural topic modelling (STM) applied to open-ended text responses. We derived an efficient five-steps STM co-analysis process for creative, inclusive, and critical engagement of data by coresearchers. Co-researchers observed that by trying to understand and impact public opinion, their own perspectives also changed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pre clinical and clinical studies of the effects of resveratrol, a phytochemical with potential chemopreventive efficacy

Resveratrol, found in grape skins and red wine, has potential chemopreventive activity in vitro at concentrations ≥5μM. This project explored the tolerability, pharmacokinetics and pharmacodynamics of resveratrol in two clinical phase 1 studies. In vivo data were supported by in vitro studies designed to mimic the daily dosing protocol, using concentrations observed clinically. Forty healthy volunteers received 29 oral daily doses of 0.5, 1.0, 2.5 and 5.0g resveratrol and 20 colorectal cancer patients 8 oral daily doses of 0.5 and 1.0g prior to surgical resection. The pharmacodynamics of resveratrol were assessed by measuring changes in plasma levels of proteins involved in the IGF system, oxidative DNA damage in whole blood and colorectal tissue (M1dG), effects on inflammatory pathways in plasma (PGE2) and colorectal tissue (COX-2), as well as colorectal tissue proliferation (Ki-67). No serious adverse events were reported. In volunteers, mean peak plasma levels of resveratrol across the dose groups ranged from 44.7-954ng/mL (0.20-4.20μM), and for the main metabolite, resveratrol-3-sulfate, were 4-13 fold-higher. Despite low systemic bioavailability, resveratrol concentrations associated with potential chemopreventive efficacy were observed in colorectal tumour tissue with a mean of 44.0nmol/g detected in patients receiving the 1.0g dose (range 0.30-195nmol/g). Post dosing, IGF-1 levels were reduced by 8% (P=0.03) in volunteers and by 33% (P<0.001) in colorectal cancer patients. In tissue, a reduction in cell proliferation of 5.5% (P=0.05) was observed, whilst there was an increase in COX-2 staining (P=0.004). Apart from the 2.5g dose in volunteers, where a significant increase was observed in blood M1dG (21.6%, P=0.02), resveratrol did not significantly affect plasma PGE2 or markers of DNA damage in either study. In cultured colon cancer cells, daily exposure to resveratrol was associated with increased antiproliferative activity compared to an equivalent single dose, supporting the indication that chronic administration may cause pharmacodynamic changes in humans. The work presented here suggests resveratrol has potential as a cancer chemopreventive agent and controlled clinical trials are now warranted.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A reflection on dialogic diving boards and decolonising school art: The African mask project

In this paper, four colleagues working in teacher education reflect on a conversation. The conversation in question was a tangible discussion documented through frequent and purposeful email exchange, exploring traditionalist school art curricula through reference to lived experience, academic theory, and professional anecdote. The primary objective of this dialogic self‐enquiry was informal critical analysis of the cultural diversity and positioning of art objects that populate classroom curricula in English schools, starting with the ‘African mask’. The secondary objective of our conversation was exploration of how complex talk on culture and curriculum might be modelled for schoolteachers yet to initiate similar conversations in their own professional contexts. We each provide reflections on the success of our conversation against these objectives and find that while email exchange provided some formal advantages for the structure of our discourse, this was not as we might have expected. The dialogue facilitated a rhizomatic deepening of our individual questioning of culturality in the classroom, which while nourishing was arguably unproductive in instrumental terms. Collectively, our reflections suggest that dialogue may be a critical catalyst for the latter, inherently private work of decolonising one's own critical teaching praxis

Individual trophic specialization in juvenile European seabass: implications for the management of a commercially important species

Individual differences in diet can play an important role defining a population's ecological niche and its role within food webs and habitats, but individual trophic specialization is rarely considered in a fisheries context. Stocks of European seabass, Dicentrarchus labrax, have declined in recent years, and policy has focused on managing fishing effort. Inshore nursery grounds represent a critical habitat in terms of recruitment to standing stocks, and improved understanding of the ecology of juvenile seabass at the level of the individual may assist the development of management strategies aimed at maximizing their survival and growth. We quantified levels of individual trophic specialization in juvenile seabass using stomach contents and stable isotope analyses at a monthly resolution over an annual cycle. We found significant, seasonally varying levels of individual specialization in stomach contents, with reduced specialization observed in the spring. This was corroborated by stable isotope analyses, where isotopic variance among seabass individuals was significantly higher compared to that in two other concurrently sampled, sympatric bentho-pelagic predators. Our findings suggest that juvenile seabass form trophic-generalist populations composed of specialized individuals. Considering variation in individual behaviours may improve management strategies aimed at protecting the vulnerable life stages of this commercially important species