Does a biomedical research centre affect patient care in local hospitals?

BACKGROUND: Biomedical research can have impacts on patient care at research-active hospitals. We qualitatively evaluated the impact of the Oxford Biomedical Research Centre (Oxford BRC), a university-hospital partnership, on the effectiveness and efficiency of healthcare in local hospitals. Effectiveness and efficiency are conceptualised in terms of impacts perceived by clinicians on the quality, quantity and costs of patient care they deliver. METHODS: First, we reviewed documentation from Oxford BRC and literature on the impact of research activity on patient care. Second, we interviewed leaders of the Oxford BRC's research to identify the direct and indirect impacts they expected their activity would have on local hospitals. Third, this information was used to inform interviews with senior clinicians responsible for patient care at Oxford's acute hospitals to discover what impacts they observed from research generally and from Oxford BRC's research work specifically. We compared and contrasted the results from the two sets of interviews using a qualitative approach. Finally, we identified themes emerging from the senior clinicians' responses, and compared them with an existing taxonomy of mechanisms through which quality of healthcare may be affected in research-active settings. RESULTS: We were able to interview 17 research leaders at the Oxford BRC and 19 senior clinicians at Oxford's acute hospitals. The research leaders identified a wide range of beneficial impacts that they expected might be felt at local hospitals as a result of their research activity. They expected the impact of their research activity on patient care to be generally positive. The senior clinicians responsible for patient care at those hospitals presented a more mixed picture, identifying many positive impacts, but also a smaller number of negative impacts, from research activity, including that of the Oxford BRC. We found the existing taxonomy of benefit types to be helpful in organising the findings, and propose modifications to further improve its usefulness. CONCLUSIONS: Impacts from research activity on the effectiveness and efficiency of patient care at the local acute hospitals, as perceived by senior clinicians, were more often beneficial than harmful. The Oxford BRC contributed to those impacts.

Unmixing of fluorescence spectra to resolve quantitative time-series measurements of gene expression in plate readers.

BACKGROUND: To connect gene expression with cellular physiology, we need to follow levels of proteins over time. Experiments typically use variants of Green Fluorescent Protein (GFP), and time-series measurements require specialist expertise if single cells are to be followed. Fluorescence plate readers, however, a standard in many laboratories, can in principle provide similar data, albeit at a mean, population level. Nevertheless, extracting the average fluorescence per cell is challenging because autofluorescence can be substantial. RESULTS: Here we propose a general method for correcting plate reader measurements of fluorescent proteins that uses spectral unmixing and determines both the fluorescence per cell and the errors on that fluorescence. Combined with strain collections, such as the GFP fusion collection for budding yeast, our methodology allows quantitative measurements of protein levels of up to hundreds of genes and therefore provides complementary data to high throughput studies of transcription. We illustrate the method by following the induction of the GAL genes in Saccharomyces cerevisiae for over 20 hours in different sugars and argue that the order of appearance of the Leloir enzymes may be to reduce build-up of the toxic intermediate galactose-1-phosphate. Further, we quantify protein levels of over 40 genes, again over 20 hours, after cells experience a change in carbon source (from glycerol to glucose). CONCLUSIONS: Our methodology is sensitive, scalable, and should be applicable to other organisms. By allowing quantitative measurements on a per cell basis over tens of hours and over hundreds of genes, it should increase our understanding of the dynamic changes that drive cellular behaviour.

Understanding mental health in the research environment: A Rapid Evidence Assessment.

This study aimed to establish what is known about the mental health of researchers based on the existing literature. There is limited published evidence on the prevalence of specific mental health conditions among researchers. The majority of the identified literature on prevalence relates to work-related stress among academic staff and postgraduate students in university settings. Survey data indicate that the majority of university staff find their job stressful. Levels of burnout appear higher among university staff than in general working populations and are comparable to "high-risk" groups such as healthcare workers. The proportions of both university staff and postgraduate students with a risk of having or developing a mental health problem, based on self-reported evidence, were generally higher than for other working populations. Large proportions (>40 per cent) of postgraduate students report symptoms of depression, emotion or stress-related problems, or high levels of stress. Factors including increased job autonomy, involvement in decision making and supportive management were linked to greater job satisfaction among academics, as was the amount of time spent on research. Opportunities for professional development were also associated with reduced stress. UK higher education (HE) and research staff report worse wellbeing, as compared to staff in other sectors, in most aspects of work that can affect workers' stress levels. The evidence around the effectiveness of interventions to support the mental health of researchers specifically is thin. Few interventions are described in the literature and even fewer of those have been evaluated.

Transforming Urgent and Emergency Care and the Vanguard Initiative: Learning from Evaluation of the Southern Cluster.

Urgent and Emergency Care (UEC) vanguards aim to improve the quality, efficiency and effectiveness of UEC services so that patients receive the most appropriate care at the right time and in the right place, and so that unnecessary admissions to accident and emergency (A&E) and hospitals are reduced. The Southern Cluster comprises three such UEC vanguards. RAND Europe's evaluation examined the impacts of the vanguards, the processes underpinning delivery (and associated enablers and challenges), and implications for future policy and practice. The evaluation used a multi-method approach, including theories of change, document review, workshops, interviews, surveys and data dashboards. The Southern Cluster UEC vanguards have made progress across core activities. Clinical hubs are operational across the sites. Direct booking capacity into primary care is progressing more with out-of-hours than with in-hours services. Gradual but variable progress has been made towards joint planning and governance of UEC services. Efforts to ensure seamless data sharing between providers, and interoperable IT infrastructure are progressing somewhat slower than originally hoped. Vanguard funding, committed leadership and practical mechanisms to support joint working helped drive progress. Public engagement, workforce-capacity and data interoperability will need to be addressed for longer-term impact at scale. The study makes recommendations concerning: (i) UEC health and care workforce capacity-building, (ii) local-national coordination around UEC transformation, (iii) collaboration across localities and professions, (iv) support for an end-to-end UEC pathway with mutually reinforcing activities, (v) cost and outcome data, (vi) an interoperable data infrastructure, and (vii) capacity for evaluation and learning.

100 Metrics to Assess and Communicate the Value of Biomedical Research: An Ideas Book.

Biomedical research affects society in many ways. It has been shown to improve health, create jobs, add to our knowledge, and foster new collaborations. Despite the complexity of modern research, many of the metrics used to evaluate the impacts of research still focus on the traditional, often academic, part of the research pathway, covering areas such as the amount of grant funding received and the number of peer-reviewed publications. In response to increasing expectations of accountability and transparency, the Association of American Medical Colleges (AAMC), in collaboration with RAND Europe, undertook a project to help communicate the wider value of biomedical research. The initiative developed resources to support academic medical centers in evaluating the outcomes and impacts of their research using approaches relevant to various stakeholders, including patients, providers, administrators, and legislators. This study presents 100 ideas for metrics that can be used to assess and communicate the value of biomedical research. The list is not comprehensive, and the metrics are not fully developed, but they should serve to stimulate and broaden thinking about how academic medical centers can communicate the value of their research to a broad range of stakeholders.

Mapping the Global Mental Health Research Funding System.

This study maps the global funding of mental health research between 2009 and 2014. It builds from the bottom up a picture of who the major funders are, what kinds of research they support and how their strategies relate to one another. It uses the funding acknowledgements on journal papers as a starting point for this. The study also looks to the future, considering some of the areas of focus, challenges and opportunities which may shape the field in the coming few years.

How policy can help develop and sustain workforce capacity in UK dementia research: insights from a career tracking analysis and stakeholder interviews.

OBJECTIVES: To identify research support strategies likely to be effective for strengthening the UK's dementia research landscape and ensuring a sustainable and competitive workforce. DESIGN: Interviews and qualitative analysis; systematic internet search to track the careers of 1500 holders of UK doctoral degrees in dementia, awarded during 1970-2013, to examine retention in this research field and provide a proxy profile of the research workforce. SETTING AND PARTICIPANTS: 40 interviewees based in the UK, whose primary role is or has been in dementia research (34 individuals), health or social care (3) or research funding (3). Interviewees represented diverse fields, career stages and sectors. RESULTS: While the UK has diverse strengths in dementia research, needs persist for multidisciplinary collaboration, investment in care-related research, supporting research-active clinicians and translation of research findings. There is also a need to better support junior and midlevel career opportunities to ensure a sustainable research pipeline and future leadership. From a sample of 1500 UK doctorate holders who completed a dementia-related thesis in 1970-2013, we identified current positions for 829 (55%). 651 (43% of 1500) could be traced and identified as still active in research (any field) and 315 (21%) as active in dementia research. Among recent doctoral graduates, nearly 70% left dementia research within 4-6 years of graduation. CONCLUSIONS: A dementia research workforce blueprint should consider support for individuals, institutions and networks. A mix of policy interventions are needed, aiming to attract and retain researchers; tackle bottlenecks in career pathways, particularly at early and midcareer stages (eg, scaling-up fellowship opportunities, rising star programmes, bridge-funding, flexible clinical fellowships, leadership training); and encourage research networks (eg, doctoral training centres, succession and sustainability planning). Interventions should also address the need for coordinated investment to improve multidisciplinary collaboration; balanced research portfolios across prevention, treatment and care; and learning from evaluation.

The future of anticoagulation management in atrial fibrillation in Europe: An assessment of today's challenges with recommendations for the future.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting approximately 1-2 per cent of the population worldwide. Those who suffer from AF have a five times higher risk of stroke. AF prevalence increases with age and it affects roughly 18 per cent of the population over 85. Consequently, as populations age, AF is becoming an increasingly significant public health issue. Over recent years there have been developments in treatment and management options, both for treating the arrhythmia directly, and assessing and reducing the risk of AF-related stroke, but there is a need to ensure that available knowledge is applied optimally to benefit patients so that opportunities to prevent AF-related stroke are not missed. The aims of this project were to assess the current landscape and explore the direction of future developments in AF management in Europe, with a focus on the use of anticoagulants in the prevention of AF-related stroke. Through rapid evidence assessment, key informant interviews, PESTLE analysis and the development and exploration of future scenarios, we have developed sets of shorter- and longer-term recommendations for improving AF-related patient outcomes. The short-term recommendations are: i) improve AF awareness among the public and policymakers; ii) support education about AF management for healthcare professionals and patients; and iii) maintain engagement in AF-related research across the health services.

A Bayesian method for inferring quantitative information from FRET data.

BACKGROUND: Understanding biological networks requires identifying their elementary protein interactions and establishing the timing and strength of those interactions. Fluorescence microscopy and Förster resonance energy transfer (FRET) have the potential to reveal such information because they allow molecular interactions to be monitored in living cells, but it is unclear how best to analyze FRET data. Existing techniques differ in assumptions, manipulations of data and the quantities they derive. To address this variation, we have developed a versatile Bayesian analysis based on clear assumptions and systematic statistics. RESULTS: Our algorithm infers values of the FRET efficiency and dissociation constant, Kd, between a pair of fluorescently tagged proteins. It gives a posterior probability distribution for these parameters, conveying more extensive information than single-value estimates can. The width and shape of the distribution reflects the reliability of the estimate and we used simulated data to determine how measurement noise, data quantity and fluorophore concentrations affect the inference. We are able to show why varying concentrations of donors and acceptors is necessary for estimating Kd. We further demonstrate that the inference improves if additional knowledge is available, for example of the FRET efficiency, which could be obtained from separate fluorescence lifetime measurements. CONCLUSIONS: We present a general, systematic approach for extracting quantitative information on molecular interactions from FRET data. Our method yields both an estimate of the dissociation constant and the uncertainty associated with that estimate. The information produced by our algorithm can help design optimal experiments and is fundamental for developing mathematical models of biochemical networks.