The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Medical Students As Standardized Patients In A Second-Year Performance-Based Assessment Experience

: Performance-based assessments of medical students using standardized patients (SPs) have been conducted in a variety of formats during both pre-clinical and clinical years. At Michigan State University College of Human Medicine, a series of performance-based assessment (PBA) experiences have been established in the second year to evaluate students' abilities to integrate basic skills and medical knowledge. The format developed was based on classmates acting as SPs. The PBA experiences were perceived by students as being effective in reinforcing the goals of the curriculum and the format was viewed positively. The smallgroup learning experience provided by the patient training session was valued by students, and was an important part of their positive attitude toward the time required for acting as an SP. Thus using students as SPs can be an excellent cost-effective approach for performance-based assessments used as formative evaluation. Performance-based assessments of medi..

Carers' experiences of involvement in care planning: a qualitative exploration of the facilitators and barriers to engagement with mental health services.

BACKGROUND: Formal recognition and involvement of carers in mental health services has been the focus of recent policy and practice initiatives as well as being supported by carers themselves. However, carers still report feeling marginalised and distanced from services. A prominent theme is that that they are not listened to and their concerns are not taken seriously. Compared to service user views, the reasons underpinning carers’ dissatisfaction with care-planning procedures have been relatively neglected in the research literature, despite the substantial and significant contribution that they make to mental health services. The aim of the study was to explore carers’ experiences of the care planning process for people with severe mental illness. METHODS: Qualitative interviews and focus groups were undertaken with carers. Data were combined and analysed using framework analysis. RESULTS: Whilst identifying a shared desire for involvement and confirming a potential role for carers within services, our data highlighted that many carers perceive a lack of involvement in care planning and a lack of recognition and appreciation of their role from health professionals. Barriers to involvement included structural barriers, such as the timing and location of meetings, cultural barriers relating to power imbalances within the system and specific barriers relating to confidentiality. CONCLUSIONS: This qualitative study led by a researcher who was a carer herself has developed the understanding of the potential role of carers within the care planning process within mental health services, along with the facilitators and barriers to achieving optimal involvement

Gene duplication and environmental adaptation within yeast populations

Population-level differences in the number of copies of genes resulting from gene duplication and loss have recently been recognized as an important source of variation in eukaryotes. However, except for a small number of cases, the phenotypic effects of this variation are unknown. Data from the Saccharomyces Genome Resequencing Project permit the study of duplication in genome sequences from a set of individuals within the same population. These sequences can be correlated with available information on the environments from which these yeast strains were isolated. We find that yeast show an abundance of duplicate genes that are lineage specific, leading to a large degree of variation in gene content between individual strains. There is a detectable bias for specific functions, indicating that selection is acting to preferentially retain certain duplicates. Most strikingly, we find that sets of over- and underrepresented duplicates correlate with the environment from which they were isolated. Together, these observations indicate that gene duplication can give rise to substantial phenotypic differences within populations that in turn can offer a shortcut to evolutionary adaptation