A molecular and cellular analysis of human embryonic optic fissure closure related to the eye malformation coloboma

Ocular coloboma is a congenital eye malformation, resulting from a failure in optic fissure closure (OFC), and causing visual impairment. There has been little study of the epithelial fusion process underlying closure in the human embryo and coloboma aetiology remains poorly understood. We performed RNAseq of cell populations isolated using laser capture microdissection to identify novel human OFC signature genes and probe the expression profile of known coloboma genes, along with a comparative murine analysis. Gene set enrichment patterns showed conservation between species. Expression of genes involved in epithelial-to-mesenchymal transition was transiently enriched in the human fissure margins during OFC at days 41-44. Electron microscopy and histological analyses showed that cells transiently delaminate at the point of closure, and produce cytoplasmic protrusions, before rearranging to form two continuous epithelial layers. Apoptosis was not observed in the human fissure margins. These analyses support a model of human OFC in which epithelial cells at the fissure margins undergo a transient epithelial-to-mesenchymal-like transition, facilitating cell rearrangement to form a complete optic cup

The 20-item prosopagnosia index (PI20): a self-report instrument for identifying developmental prosopagnosia

Self-report plays a key role in the identification of developmental prosopagnosia (DP), providing complementary evidence to computer-based tests of face recognition ability, aiding interpretation of scores. However, the lack of standardized self-report instruments has contributed to heterogeneous reporting standards for self-report evidence in DP research. The lack of standardization prevents comparison across samples and limits investigation of the relationship between objective tests of face processing and self-report measures. To address these issues, this paper introduces the PI20; a 20-item self-report measure for quantifying prosopagnosic traits. The new instrument successfully distinguishes suspected prosopagnosics from typically developed adults. Strong correlations were also observed between PI20 scores and performance on objective tests of familiar and unfamiliar face recognition ability, confirming that people have the necessary insight into their own face recognition ability required by a self-report instrument. Importantly, PI20 scores did not correlate with recognition of non-face objects, indicating that the instrument measures face recognition, and not a general perceptual impairment. These results suggest that the PI20 can play a valuable role in identifying DP. A freely available self-report instrument will permit more effective description of self-report diagnostic evidence, thereby facilitating greater comparison of prosopagnosic samples, and more reliable classification

Population tobacco control interventions and their effects on social inequalities in smoking: systematic review

OBJECTIVE: To assess the effects of population tobacco control interventions on social inequalities in smoking. DATA SOURCES: Medical, nursing, psychological, social science and grey literature databases, bibliographies, hand-searches and contact with authors. STUDY SELECTION: Studies were included (n = 84) if they reported the effects of any population-level tobacco control intervention on smoking behaviour or attitudes in individuals or groups with different demographic or socioeconomic characteristics. DATA EXTRACTION: Data extraction and quality assessment for each study were conducted by one reviewer and checked by a second. DATA SYNTHESIS: Data were synthesised using graphical ("harvest plot") and narrative methods. No strong evidence of differential effects was found for smoking restrictions in workplaces and public places, although those in higher occupational groups may be more likely to change their attitudes or behaviour. Smoking restrictions in schools may be more effective in girls. Restrictions on sales to minors may be more effective in girls and younger children. Increasing the price of tobacco products may be more effective in reducing smoking among lower-income adults and those in manual occupations, although there was also some evidence to suggest that adults with higher levels of education may be more price-sensitive. Young people aged under 25 are also affected by price increases, with some evidence that boys and non-white young people may be more sensitive to price. CONCLUSIONS: Population-level tobacco control interventions have the potential to benefit more disadvantaged groups and thereby contribute to reducing health inequalities

Using automation to produce a ‘living map’ of the COVID-19 research literature

The COVID-19 pandemic has disrupted life worldwide and presented unique challenges in the health evidencesynthesis space. The urgent nature of the pandemic required extreme rapidity for keeping track of research, andthis presented a unique opportunity for long-proposed automation systems to be deployed and evaluated. Wecompared the use of novel automation technologies with conventional manual screening; and Microsoft AcademicGraph (MAG) with the MEDLINE and Embase databases locating the emerging research evidence. We foundthat a new workflow involving machine learning to identify relevant research in MAG achieved a much higherrecall with lower manual effort than using conventional approaches

Cost-effectiveness of Microsoft Academic Graph with machine learning for automated study identification in a living map of coronavirus disease 2019 (COVID-19) research

BACKGROUND: Conventionally, searching for eligible articles to include in systematic reviews and maps of research has relied primarily on information specialists conducting Boolean searches of multiple databases and manually processing the results, including deduplication between these multiple sources. Searching one, comprehensive source, rather than multiple databases, could save time and resources. Microsoft Academic Graph (MAG) is potentially such a source, containing a network graph structure which provides metadata that can be exploited in machine learning processes. Research is needed to establish the relative advantage of using MAG as a single source, compared with conventional searches of multiple databases. This study sought to establish whether: (a) MAG is sufficiently comprehensive to maintain our living map of coronavirus disease 2019 (COVID-19) research; and (b) eligible records can be identified with an acceptably high level of specificity. METHODS: We conducted a pragmatic, eight-arm cost-effectiveness analysis (simulation study) to assess the costs, recall and precision of our semi-automated MAG-enabled workflow versus conventional searches of MEDLINE and Embase (with and without machine learning classifiers, active learning and/or fixed screening targets) for maintaining a living map of COVID-19 research. Resource use data (time use) were collected from information specialists and other researchers involved in map production. RESULTS: MAG-enabled workflows dominated MEDLINE-Embase workflows in both the base case and sensitivity analyses. At one month (base case analysis) our MAG-enabled workflow with machine learning, active learning and fixed screening targets identified n=469 more new, eligible articles for inclusion in our living map – and cost £3,179 GBP ($5,691 AUD) less – than conventional MEDLINE-Embase searches without any automation or fixed screening targets. CONCLUSIONS: MAG-enabled continuous surveillance workflows have potential to revolutionise study identification methods for living maps, specialised registers, databases of research studies and/or collections of systematic reviews, by increasing their recall and coverage, whilst reducing production costs

Advancing practice for back pain through stratified care (STarT Back)

Background Low back pain (LBP) is common, however research comparing the effectiveness of different treatments over the last two decades conclude either no or small differences in the average effects of different treatments. One suggestion to explain this is that patients are not all the same and important subgroups exist that might require different treatment approaches. Stratified care for LBP involves identifying subgroups of patients and then delivering appropriate matched treatments. Research has shown that stratified care for LBP in primary care can improve clinical outcomes, reduce costs and increase the efficiency of health-care delivery in the UK. The challenge now is to replicate and evaluate this approach in other countries health care systems and to support services to implement it in routine clinical care. Results The STarT Back approach to stratified care has been tested in the National Health Service, within the UK, it reduces unnecessary overtreatment in patients who have a good prognosis (those at low risk) yet increases the likelihood of appropriate healthcare and associated improved outcomes for those who are at risk of persistent disabling pain. The approach is cost-effective in the UK healthcare setting and has been recommended in recent guidelines and implemented as part of new LBP clinical pathways of care. This approach has subsequently generated international interest, a replication study is currently underway in Denmark, however, some lessons have already been learnt. There are potential obstacles to implementing stratified care in low-and-middle-income settings and in other high-income settings outside of the UK, however, implementation science literature can inform the development of innovations and efforts to support implementation of stratified care. Conclusions The STarT Back approach to stratified care for LBP is a promising method to advance practice that has demonstrated clinical and cost effectiveness in the UK. Over time, further evidence for both the effectiveness and the adaptations needed to test and implement the STarT Back stratified care approach in other countries is needed

The Bivariate Normal Copula

We collect well known and less known facts about the bivariate normal distribution and translate them into copula language. In addition, we prove a very general formula for the bivariate normal copula, we compute Gini's gamma, and we provide improved bounds and approximations on the diagonal.Comment: 24 page

Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669)

Background Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. Methods/Design This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. Discussion This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Trial registration Current Controlled Trials ISRCTN52269669