Research output on primary care in Australia, Canada, Germany, the Netherlands, the United Kingdom, and the United States: bibliometric analysis

Objective To compare the volume and quality of original research in primary care published by researchers from primary care in the United Kingdom against five countries with well established academic primary care

Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

Challenges in microbial ecology: building predictive understanding of community function and dynamics.

The importance of microbial communities (MCs) cannot be overstated. MCs underpin the biogeochemical cycles of the earth's soil, oceans and the atmosphere, and perform ecosystem functions that impact plants, animals and humans. Yet our ability to predict and manage the function of these highly complex, dynamically changing communities is limited. Building predictive models that link MC composition to function is a key emerging challenge in microbial ecology. Here, we argue that addressing this challenge requires close coordination of experimental data collection and method development with mathematical model building. We discuss specific examples where model-experiment integration has already resulted in important insights into MC function and structure. We also highlight key research questions that still demand better integration of experiments and models. We argue that such integration is needed to achieve significant progress in our understanding of MC dynamics and function, and we make specific practical suggestions as to how this could be achieved

Access to health care for people with learning disabilities in the UK: Mapping the issues and reviewing the evidence

BACKGROUND: People with learning disabilities are more prone to a wide range of additional physical and mental health problems than the general population. This paper seeks to map the issues and review the evidence on access to healthcare for these patients. The review aimed to identify theory, evidence and gaps in knowledge relating to the help-seeking behaviour of people with learning disabilities and their carers; barriers and problems they experience accessing the full range of health services; and practical and effective interventions aiming to improve access to healthcare. METHODS: A three strand approach was adopted, including searches of electronic databases, a consultation exercise, and a mail shot to researchers and learning disability health professionals. Evidence relevant to our model of ‘access’ was evaluated for scientific rigour and selected papers synthesised. FINDINGS: Overall, a lack of rigorous research in this area was noted and significant gaps in the evidence base were apparent. Evidence was identified on the difficulties identifying health needs among people with learning disabilities and the potentially empowering or obstructive influence of third parties on access to healthcare. Barriers to access identified within health services included problems with communication, inadequate facilities or rigid procedures, and lack of interpersonal skills amongst mainstream health professionals in caring for these patients. A number of innovations designed to improve access were identified, including a communication aid, a prompt card to support general practitioners, health check programmes and walk-in clinics. However the effectiveness of these strategies in improving access to appropriate healthcare remains to be established

PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews

BACKGROUND: Qualitative systematic reviews are increasing in popularity in evidence based health care. Difficulties have been reported in conducting literature searches of qualitative research using the PICO search tool. An alternative search tool, entitled SPIDER, was recently developed for more effective searching of qualitative research, but remained untested beyond its development team. METHODS: In this article we tested the ‘SPIDER’ search tool in a systematic narrative review of qualitative literature investigating the health care experiences of people with Multiple Sclerosis. Identical search terms were combined into the PICO or SPIDER search tool and compared across Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL Plus databases. In addition, we added to this method by comparing initial SPIDER and PICO tools to a modified version of PICO with added qualitative search terms (PICOS). RESULTS: Results showed a greater number of hits from the PICO searches, in comparison to the SPIDER searches, with greater sensitivity. SPIDER searches showed greatest specificity for every database. The modified PICO demonstrated equal or higher sensitivity than SPIDER searches, and equal or lower specificity than SPIDER searches. The modified PICO demonstrated lower sensitivity and greater specificity than PICO searches. CONCLUSIONS: The recommendations for practice are therefore to use the PICO tool for a fully comprehensive search but the PICOS tool where time and resources are limited. Based on these limited findings the SPIDER tool would not be recommended due to the risk of not identifying relevant papers, but has potential due to its greater specificity