Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models

Over the past 20 years, huge advances have been made in modelling human diseases such as cancer using genetically modified mice. Accurate in vivo models are essential to examine the complex interaction between cancer cells, surrounding stromal cells, tumour-associated inflammatory cells, fibroblast and blood vessels, and to recapitulate all the steps involved in metastasis. Elucidating these interactions in vitro has inherent limitations, and thus animal models are a powerful tool to enable researchers to gain insight into the complex interactions between signalling pathways and different cells types. This review will focus on how advances in in vivo models have shed light on many aspects of cancer biology including the identification of oncogenes, tumour suppressors and stem cells, epigenetics, cell death and context dependent cell signalling

Electricity Market Operation: Transitioning from a Free Market to a Single Buyer structure: An econometric analysis of the Brazilian case using a Two-State Markov Switching Model

We examine electricity market reform in Brazil: from the 1990s till 2004 the largely hydro-powered market cleared using a market mechanism, and in March 2004 reformed to a single buyer structure. We model day-ahead returns using a Two-State Markov Switching Model with dummy variable analysis, allowing water storage and natural inflows to affect returns and volatility. Our results indicate the single buyer structure decreased volatility during stable periods but worsened energy crises. Post-reform, we find a more forgiving environment for the allocation of stored energy given natural water inflows, however sub-optimal water management leads to energy crises developing

Evidence that heat acclimation training may alter sleep and incidental activity

This randomized cross-over study tested the hypothesis that heat acclimation training would detrimentally affect sleep variables and alter incidental physical activity compared to a thermoneutral training control condition. Eight recreationally trained males (V̇ O2peak 49±4.9 mL. kg-1.min-1) completed two separate interventions separated by at least 31 days: 5 consecutive day training blocks of moderate-intensity cycling (60 min·day-1 at 50% peak power output) in a hot (34.9±0.7 °C and 53±4 % relative humidity) and a temperate (22.2±2.6 °C; 65±8 % relative humidity) environment. Wrist-mounted accelerometers were worn continuously for the length of the training blocks and recorded physical activity, sleep quality and quantity. Data were analysed in a Bayesian framework, with the results presented as the posterior probability that a coefficient was greater or less than zero. Compared to the temperate training environment, heat acclimation impaired sleep efficiency (Pr β0 = .917). Daily sedentary time was, on average, 35 min longer (Pr β>0 = .973) and light physical activity time 18 min shorter (Pr β>0 = .960) during the heat acclimation period. No differences were observed between conditions in sleep duration, subjective sleep quality, or moderate or vigorous physical activity. These findings may suggest that athletes and coaches need to be cognisant that heat acclimation training may alter sleep quality and increase sedentary behaviour

Years of good life based on income and health: re-engineering cost-benefit analysis to examine policy impacts on wellbeing and distributive justice

In this paper, we propose a practical measure of individual wellbeing to facilitate the economic evaluation of public policies. We propose to evaluate policies in terms of years of good life gained, in a way that complements and generalises conventional cost-benefit analysis in terms of money. We aim to show how years of good life could be measured in practice by harnessing readily available data on three important elements of individual wellbeing: income, health-related quality of life, and longevity. We also aim to identify the main ethical assumptions needed to use this measure

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

Summary Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model

Conservation measures or hotspots of disease transmission? Agri-environment schemes can reduce disease prevalence in pollinator communities

Insects are under pressure from agricultural intensification. To protect pollinators, conservation measures such as the EU agri-environment schemes (AES) promote planting wildflowers along fields. However, this can potentially alter disease ecology by serving as transmission hubs or by diluting infections. We tested this by measuring plant–pollinator interactions and virus infections (DWV-A, DWV-B and ABPV) across pollinator communities in agricultural landscapes over a year. AES had a direct effect on DWV-B, reducing prevalence and load in honeybees, with a tentative general dilution effect on load in early summer. DWV-A prevalence was reduced both under AES and with increasing niche overlap between competent hosts, likely via a dilution effect. By contrast, AES had no impact on ABPV, its prevalence driven by the proportion of bumblebees in the community. Epidemiological differences were also reflected in the virus phylogenies, with DWV-B showing recent rapid expansion, while DWV-A and ABPV showed slower growth rates and geographical population structure. Phylogenies indicate that all three viruses freely circulate across their host populations. Our study illustrates how complex interactions between environmental, ecological and evolutionary factors may influence wildlife disease dynamics. Supporting pollinator nutrition can mitigate the transmission of important bee diseases, providing an unexpected boost to pollinator conservation

Controversies in the Science of Sedentary Behaviour and Health: Insights, Perspectives and Future Directions from the 2018 Queensland Sedentary Behaviour Think Tank

The development in research concerning sedentary behaviour has been rapid over the past two decades. This has led to the development of evidence and views that have become more advanced, diverse and, possibly, contentious. These include the effects of standing, the breaking up of prolonged sitting and the role of moderate-to-vigorous physical activity (MVPA) in the association between sedentary behaviour and health outcomes. The present aim is to report the views of experts (n = 21) brought together (one-day face-to-face meeting in 2018) to consider these issues and provide conclusions and recommendations for future work. Each topic was reviewed and presented by one expert followed by full group discussion, which was recorded, transcribed and analysed. The experts concluded that (a). standing may bring benefits that accrue from postural shifts. Prolonged (mainly static) standing and prolonged sitting are both bad for health; (b). ‘the best posture is the next posture’. Regularly breaking up of sitting with postural shifts and movement is vital; (c). health effects of prolonged sitting are evident even after controlling for MVPA, but high levels of MVPA can attenuate the deleterious effects of prolonged sitting depending on the health outcome of interest. Expert discussion addressed measurement, messaging and future directions

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy