The complex relationship between weather and dengue virus transmission in Thailand.

Using a novel analytical approach, weather dynamics and seasonal dengue virus transmission cycles were profiled for each Thailand province, 1983-2001, using monthly assessments of cases, temperature, humidity, and rainfall. We observed systematic differences in the structure of seasonal transmission cycles of different magnitude, the role of weather in regulating seasonal cycles, necessary versus optimal transmission "weather-space," basis of large epidemics, and predictive indicators that estimate risk. Larger epidemics begin earlier, develop faster, and are predicted at Onset change-point when case counts are low. Temperature defines a viable range for transmission; humidity amplifies the potential within that range. This duality is central to transmission. Eighty percent of 1.2 million severe dengue cases occurred when mean temperature was 27-29.5°C and mean humidity was > 75%. Interventions are most effective when applied early. Most cases occur near Peak, yet small reductions at Onset can substantially reduce epidemic magnitude. Monitoring the Quiet-Phase is fundamental in effectively targeting interventions pre-emptively

Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process

Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded several times and then unfolded. Here we adapt such methods to study the breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2^(n(n-1)/2) qualitatively distinct evolutions involving n breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the fold positions, to determine evolution likelihoods, and also describe how amplicons become localised. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples

Generic prognostic factors for musculoskeletal pain in primary care: a systematic review.

OBJECTIVES: To summarise the evidence for generic prognostic factors across a range of musculoskeletal (MSK) conditions. SETTING: primary care. METHODS AND OUTCOMES: Comprehensive systematic literature review. MEDLINE, CINAHL, PsychINFO and EMBASE were searched for prospective cohort studies, based in primary care (search period-inception to December 2015). Studies were included if they reported on adults consulting with MSK conditions and provided data on associations between baseline characteristics (prognostic factors) and outcome. A prognostic factor was identified as generic when significantly associated with any outcome for 2 or more different MSK conditions. Evidence synthesis focused on consistency of findings and study quality. RESULTS: 14 682 citations were identified and 78 studies were included (involving more than 48 000 participants with 18 different outcome domains). 51 studies were on spinal pain/back pain/low back pain, 12 on neck/shoulder/arm pain, 3 on knee pain, 3 on hip pain and 9 on multisite pain/widespread pain. Total quality scores ranged from 5 to 14 (mean 11) and 65 studies (83%) scored 9 or more. Out of a total of 78 different prognostic factors for which data were provided, the following factors are considered to be generic prognostic factors for MSK conditions: widespread pain, high functional disability, somatisation, high pain intensity and presence of previous pain episodes. In addition, consistent evidence was found for use of pain medications not to be associated with outcome, suggesting that this factor is not a generic prognostic factor for MSK conditions. CONCLUSIONS: This large review provides new evidence for generic prognostic factors for MSK conditions in primary care. Such factors include pain intensity, widespread pain, high functional disability, somatisation and movement restriction. This information can be used to screen and select patients for targeted treatment in clinical research as well as to inform the management of MSK conditions in primary care

Reimagining laboratory‐based immunology education in the time of COVID‐19

The pandemic has brought challenges to teaching lab and research skills. Here Nigel Francis and colleagues explore the diverse approaches taken to replace lab-based immunology teaching, explain how networks of educators have driven this innovation and discuss the importance of retaining best practice into the future

International Society of Sports Nutrition position stand: beta-alanine

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4–6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4–6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine

On the asymptotic reduction of a bifurcation equation for edge-buckling instabilities

Weakly clamped uniformly stretched thin elastic plates can experience edge buckling when subjected to a transverse pressure. This situation is revisited here for a circular plate, under the assumption of finite rotations and negligible bending stiffness in the pre-buckling range. The eigenproblem describing this instability is formulated in terms of two singularly perturbed fourth-order differential equations involving the non-dimensional bending stiffness ε>0. By using an extension of the asymptotic reduction technique proposed by Coman and Haughton (Acta Mech 55:179–200, 2006), these equations are formally reduced to a simple second-order ordinary differential equation in the limit ε→0+. It is further shown that the predictions of this reduced problem are in excellent agreement with the direct numerical simulations of the original bifurcation equations

Development and formative evaluation of the e-Health implementation toolkit

<b>Background</b> The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format.<p></p> <b>Results</b> The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls<p></p> <b>Conclusions</b> The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations

A qualitative study of primary care clinicians' views of treating childhood obesity

Background: The prevalence of childhood obesity is rising and the UK Government have stated a commitment to addressing obesity in general. One method has been to include indicators relating to obesity within the GP pay-for-performance Quality and Outcomes Framework (QOF) contract. This study aimed to explore general practitioners' and practice nurses' views in relation to their role in treating childhood obesity. Methods: We interviewed eighteen practitioners (twelve GPs and six nurses) who worked in general practices contracting with Rotherham Primary Care Trust. Interviews were face to face and semi structured. The transcribed data were analysed using framework analysis. Results: GPs and practice nurses felt that their role was to raise the issue of a child's weight, but that ultimately obesity was a social and family problem. Time constraint, lack of training and lack of resources were identified as important barriers to addressing childhood obesity. There was concern that the clinician-patient relationship could be adversely affected by discussing what was often seen as a sensitive topic. GPs and practice nurses felt ill-equipped to tackle childhood obesity given the lack of evidence for effective interventions, and were sceptical that providing diet and exercise advice would have any impact upon a child's weight. Conclusion: GPs and practice nurses felt that their role in obesity management was centred upon raising the issue of a child's weight, and providing basic diet and exercise advice. Clinicians may find it difficult to make a significant impact on childhood obesity while the evidence base for effective management remains poor. Until the lack of effective interventions is addressed, implementing additional targets (for example through the QOF) may not be effective