Documentation of a fully integrated epidemiological-demographic-macroeconomic model of Malaria: The case of Ghana

We develop a novel and fully integrated epidemiological-demographic-macroeconomic EDM-malaria simulation model framework for modelling of P. falciparum malaria transmission in Ghana. Our model framework represents a milestone, as the first fully integrated EDM model framework for any type of infectious disease. The complex specification and integration of regional epidemiological-demographic models within a malaria-focussed macroeconomic Computable General Equilibrium model is fully described and documented, and ideas are outlined for future applications to investigate the interplay between macroeconomic and health disease burdens, to measure the health and economic impacts of economic growth and malaria interventions, and to study the importance (or lack thereof) of the general omission of proper epidemiological underpinnings and integration of economic incentive feedback effects in the existing literature on macroeconomic assessment of infectious disease

The macro-economic effects of health co-benefits associated with climate change mitigation strategies

The UK government has specific targets for greenhouse gas (GHG) emission reduction to lower the risk of dangerous climate change. Strategies to reduce GHG emissions are sometimes perceived as expensive and difficult to implement but previous work has demonstrated significant potential health co-benefits from ‘Active Travel and low carbon driving’, ‘Housing Insulation/Ventilation’, and ‘Healthy Diet’ scenarios which may be attractive to policymakers. Here a Computable General Equilibrium model is used to assess the financial effects of such health co-benefits on the wider economy including changes in labour force, social security payments and healthcare costs averted. Results suggest that for all scenarios the financial impacts of the health co-benefits will be positive and increased active travel in particular is likely to make a substantial contribution, largely due to health care costs averted. Strategies to reduce GHG emissions and improve health are likely to result in substantial and increasing positive contributions to the economy which may offset some potential economic costs and thereby be seen more favourably in times of economic austerity

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

Self-healing dielectric elastomers for damage-Tolerant actuation and energy harvesting

The actuation and energy-harvesting performance of dielectric elastomers are strongly related to their intrinsic electrical and mechanical properties. For future resilient smart transducers, a fast actuation response, efficient energy-harvesting performance, and mechanical robustness are key requirements. In this work, we demonstrate that poly(styrene-butadiene-styrene) (SBS) can be converted into a self-healing dielectric elastomer with high permittivity and low dielectric loss, which can be deformed to large mechanical strains; these are key requirements for actuation and energy-harvesting applications. Using a one-step click reaction at room temperature for 20 min, methyl-3-mercaptopropionate (M3M) was grafted to SBS and reached 95.2% of grafting ratios. The resultant M3M–SBS can be deformed to a high mechanical strain of 1000%, with a relative permittivity of εr = 7.5 and a low tan δ = 0.03. When used in a dielectric actuator, it can provide 9.2% strain at an electric field of 39.5 MV m–1 and can also generate an energy density of 11 mJ g–1 from energy harvesting. After being subjected to mechanical damage, the self-healed elastomer can recover 44% of its breakdown strength during energy harvesting. This work demonstrates a facile route to produce self-healing, high permittivity, and low dielectric loss elastomers for both actuation and energy harvesting, which is applicable to a wide range of diene elastomer systems

Hydroxylases regulate intestinal fibrosis through the suppression of ERK mediated TGF-β1 signaling

Fibrosis is a complication of chronic inflammatory disorders such as inflammatory bowel disease (IBD), a condition which has limited therapeutic options and often requires surgical intervention. Pharmacologic inhibition of oxygen-sensing prolyl hydroxylases (PHD), which confer oxygen-sensitivity upon the hypoxia inducible factor (HIF) pathway, has recently been shown to have therapeutic potential in colitis, although the mechanisms involved remain unclear. Here, we investigated the impact of hydroxylase inhibition on inflammation-driven fibrosis in a murine colitis model. Mice exposed to dextran sodium sulfate followed by period of recovery developed intestinal fibrosis characterized by alterations in the pattern of collagen deposition and infiltration of activated fibroblasts. Treatment with the hydroxylase inhibitor dimethyloxalylglycine (DMOG) ameliorated fibrosis. TGF-β1 is a key regulator of fibrosis which acts through the activation of fibroblasts. Hydroxylase inhibition reduced TGF-β1-induced expression of fibrotic markers in cultured fibroblasts suggesting a direct role for hydroxylases in TGF-β1 signalling. This was at least in part due to inhibition of non-canonical activation of extracellular signal-regulated kinase (ERK) signalling. In summary, pharmacologic hydroxylase inhibition ameliorates intestinal fibrosis, through suppression of TGF-β1-dependent ERK activation in fibroblasts. We hypothesize that in addition to previously reported immunosupressive effects, hydroxylase inhibitors independently suppress pro-fibrotic pathway

Recommendations for and compliance with social restrictions during implementation of school closures in the early phase of the influenza A (H1N1) 2009 outbreak in Melbourne, Australia

Background Localized reactive school and classroom closures were implemented as part of a suite of pandemic containment measures during the initial response to influenza A (H1N1) 2009 in Melbourne, Australia. Infected individuals, and those who had been in close contact with a case, were asked to stay in voluntary home quarantine and refrain from contact with visitors for seven days from the date of symptom onset or exposure to an infected person. Oseltamivir (Tamiflu®) was available for treatment or prophylaxis. Methods We surveyed affected families through schools involved in the closures. Analyses of responses were descriptive. We characterized recommendations made to case and contact households and quantified adherence to guidelines and antiviral therapy. Results Of the 314 respondent households, 51 contained a confirmed case. The prescribed quarantine period ranged from 1-14 days, reflecting logistic difficulties in reactive implementation relative to the stated guidelines. Household-level compliance with the requirement to stay at home was high (84.5%, 95% CI 79.3,88.5) and contact with children outside the immediate family infrequent. Conclusions Levels of compliance with recommendations in our sample were high compared with other studies, likely due to heightened public awareness of a newly introduced virus of uncertain severity. The variability of reported recommendations highlighted the difficulties inherent in implementing a targeted reactive strategy, such as that employed in Melbourne, on a large scale during a public health emergency. This study emphasizes the need to understand how public health measures are implemented when seeking to evaluate their effectiveness

Integrating economic and health evidence to inform Covid-19 policy in low- and middle- income countries

This is the final version. Available on open access from F1000 Research via the DOI in this recordData availability: No data are associated with this article.Covid-19 requires policy makers to consider evidence on both population health and economic welfare. Over the last two decades, the field of health economics has developed a range of analytical approaches and contributed to the institutionalisation of processes to employ economic evidence in health policy. We present a discussion outlining how these approaches and processes need to be applied more widely to inform Covid-19 policy; highlighting where they may need to be adapted conceptually and methodologically, and providing examples of work to date. We focus on the evidential and policy needs of low- and middle-income countries; where there is an urgent need for evidence to navigate the policy trade-offs between health and economic well-being posed by the Covid-19 pandemic.Wellcome Trus

Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.

BACKGROUND: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series. METHODS: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as 'oligogenic'. RESULTS: The majority of oligogenic variant combinations consisted of a highly penetrant allele or known risk factor in combination with another rare but likely benign allele. The presence of oligogenic variants did not influence the age of onset or disease severity. After controlling for the single known major risk allele, the frequency of oligogenic variants was no different between cases and controls. CONCLUSIONS: A priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a known genetic risk factor, and it is the burden of these variants in combination with rare benign alleles that is likely to be responsible for some oligogenic associations. Controlling for this bias is essential in studies investigating a potential role for oligogenic variation in neurodegenerative diseases

Leptin mediates the increase in blood pressure associated with obesity.

Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with loss-of-function mutations in leptin and the LepR have low BP despite severe obesity. Leptin's effects on BP are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), as blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH caused a rapid reduction of BP in DIO mice, independent of changes in weight. Re-expression of LepRs in the DMH of DIO LepR-deficient mice caused an increase in BP. These studies demonstrate that leptin couples changes in weight to changes in BP in mammalian species

Integrating economic and health evidence to inform Covid-19 policy in low- and middle- income countries

Covid-19 requires policy makers to consider evidence on both population health and economic welfare. Over the last two decades, the field of health economics has developed a range of analytical approaches and contributed to the institutionalisation of processes to employ economic evidence in health policy. We present a discussion outlining how these approaches and processes need to be applied more widely to inform Covid-19 policy; highlighting where they may need to be adapted conceptually and methodologically, and providing examples of work to date. We focus on the evidential and policy needs of low- and middle-income countries; where there is an urgent need for evidence to navigate the policy trade-offs between health and economic well-being posed by the Covid-19 pandemic.</ns3:p