An intervention to facilitate 'high quality' physical education - from gymnastics to athletics

The summer edition of Research Matters included a short article on facilitating ‘high quality’ physical education and ‘high quality’ gymnastics in a city school (see Cale et al., 2011). The article provided a summary of the first phase of a research project which aimed to: i) facilitate high quality teaching and learning in physical education, and ii) identify key principles that contribute to high quality outcomes and which could be applied across the physical education curriculum. This article follows on and presents a summary of phase 2 of the research, which focused on athletics, as well as of the key findings and recommendations from the project overall

Postnatal mental health and mothers' processing of infant emotion: an eye-tracking study

BACKGROUND: Postnatal mental illnesses are associated with less maternal sensitivity. Differences in how mothers with and without mental illness process infant emotions could explain this. People with mental illness in non-perinatal populations show certain processing patterns when viewing emotional faces, but it is not clear whether these patterns are present in mothers. OBJECTIVE: Compared to mothers without affective symptoms (anxiety, depression and post-traumatic stress). Task 1 aimed to identify whether mothers with affective symptoms show an attentional bias towards negative infant faces; and Task 2 aimed to identify whether mothers with affective symptoms look less at infants' eyes compared to eyes and mouth. DESIGN: An experimental design was used in two tasks to answer the research objective. METHODS: Mothers with affective symptoms (n = 23) and without affective symptoms (n = 47) had their eye movements tracked whilst: Task 1, viewing pairs of infant faces; and Task 2, viewing morphed infant faces. RESULTS: In Task 1 mothers with affective symptoms were more likely to fixate first on neutral faces when the choice was between negative and neutral. In Task 2, no differences were found between groups. CONCLUSIONS: The findings from Task 1 are unexpected given previous research. More research is needed to identify potential explanations for this

Climate change could increase the geographic extent of Hendra virus spillover risk

Disease risk mapping is important for predicting and mitigating impacts of bat-borne viruses, including Hendra virus (Paramyxoviridae:Henipavirus), that can spillover to domestic animals and thence to humans. We produced two models to estimate areas at potential risk of HeV spillover explained by the climatic suitability for its flying fox reservoir hosts, Pteropus alecto and P. conspicillatus. We included additional climatic variables that might affect spillover risk through other biological processes (such as bat or horse behaviour, plant phenology and bat foraging habitat). Models were fit with a Poisson point process model and a log-Gaussian Cox process. In response to climate change, risk expanded southwards due to an expansion of P. alecto suitable habitat, which increased the number of horses at risk by 175–260% (110,000–165,000). In the northern limits of the current distribution, spillover risk was highly uncertain because of model extrapolation to novel climatic conditions. The extent of areas at risk of spillover from P. conspicillatus was predicted shrink. Due to a likely expansion of P. alecto into these areas, it could replace P. conspicillatus as the main HeV reservoir. We recommend: (1) HeV monitoring in bats, (2) enhancing HeV prevention in horses in areas predicted to be at risk, (3) investigate and develop mitigation strategies for areas that could experience reservoir host replacements

Climatic suitability influences species specific abundance patterns of Australian flying foxes and risk of Hendra virus spillover

Hendra virus is a paramyxovirus of Australian flying fox bats. It was first detected in August 1994, after the death of 20 horses and one human. Since then it has occurred regularly within a portion of the geographical distribution of all Australian flying fox (fruit bat) species. There is, however, little understanding about which species are most likely responsible for spillover, or why spillover does not occur in other areas occupied by reservoir and spillover hosts. Using ecological niche models of the four flying fox species we were able to identify which species are most likely linked to spillover events using the concept of distance to the niche centroid of each species. With this novel approach we found that 20 out of 27 events occur disproportionately closer to the niche centroid of two species (P. alecto and P. conspicillatus). With linear regressions we found a negative relationship between distance to the niche centroid and abundance of these two species. Thus, we suggest that the bioclimatic niche of these two species is likely driving the spatial pattern of spillover of Hendra virus into horses and ultimately humans

Medication burden in the first 5 years following diagnosis of type 2 diabetes: findings from the ADDITION-UK trial cohort.

INTRODUCTION: Individuals with screen-detected diabetes are likely to receive intensified pharmacotherapy to improve glycaemic control and general cardiometabolic health. Individuals are often asymptomatic, and little is known about the degree to which polypharmacy is present both before, and after diagnosis. We aimed to describe and characterize the pharmacotherapy burden of individuals with screen-detected diabetes at diagnosis, 1 and 5 years post-diagnosis. METHODS: The prescription histories of 1026 individuals with screen-detected diabetes enrolled in the ADDITION-UK trial of the promotion of intensive treatment were coded into general medication types at diagnosis, 1 and 5 years post-diagnosis. The association between change in the count of several medication types and age, baseline 10-year UK Prospective Diabetes Study (UKPDS) cardiovascular disease (CVD risk), sex, intensive treatment group and number of medications was explored. RESULTS: Just under half of individuals were on drugs unrelated to cardioprotection before diagnosis (42%), and this increased along with a rise in the number of prescribed diabetes-related and cardioprotective drugs. The medication profile over the first 5 years suggests multimorbidity and polypharmacy is present in individuals with screen-detected diabetes. Higher modeled CVD risk at baseline was associated with a greater increase in cardioprotective and diabetes-related medication, but not an increase in other medications. CONCLUSION: As recommended in national guidelines, our results suggest that treatment of diabetes was influenced by the underlying risk of CVD. While many individuals did not start glucose lowering and cardioprotective therapies in the first 5 years after diagnosis, more information is required to understand whether this represents unmet need, or patient-centered care. TRIAL REGISTRATION NUMBER: CNT00237549.This study was supported by the Welcome Trust (grant number G061895), the Medical Research Council (Grant numbers G0001164 and MC_UU_12015/4) and the National Institute for Health Research (Grant number RP-PG-0606-1259).This is the final version of the article. It first appeared from BMJ via http://dx.doi.org/10.1136/bmjdrc-2014-00007

A mathematical investigation into the uptake kinetics of nanoparticles in vitro.

Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Here we develop a mathematical model to simulate the uptake of polymersomes via endocytosis, a process by which polymersomes bind to the cell surface before becoming internalised by the cell where they then break down, releasing their contents which could include chemotherapy drugs. We focus on two in vitro configurations relevant to the testing and development of cancer therapies: a well-mixed culture model and a tumour spheroid setup. Our mathematical model of the well-mixed culture model comprises a set of coupled ordinary differential equations for the unbound and bound polymersomes and associated binding dynamics. Using a singular perturbation analysis we identify an optimal number of ligands on the polymersome surface which maximises internalised polymersomes and thus intracellular chemotherapy drug concentration. In our mathematical model of the spheroid, a multiphase system of partial differential equations is developed to describe the spatial and temporal distribution of bound and unbound polymersomes via advection and diffusion, alongside oxygen, tumour growth, cell proliferation and viability. Consistent with experimental observations, the model predicts the evolution of oxygen gradients leading to a necrotic core. We investigate the impact of two different internalisation functions on spheroid growth, a constant and a bond dependent function. It was found that the constant function yields faster uptake and therefore chemotherapy delivery. We also show how various parameters, such as spheroid permeability, lead to travelling wave or steady-state solutions

Novel in vitro and mathematical models for the prediction of chemical toxicity

The focus of much scientific and medical research is directed towards understanding the disease process and defining therapeutic intervention strategies. Whilst the scientific basis of drug safety has received relatively little attention, despite the fact that adverse drug reactions (ADRs) are a major health concern and a serious impediment to development of new medicines. Toxicity issues account for ~21% drug attrition during drug development and safety testing strategies require considerable animal use. Mechanistic relationships between drug plasma levels and molecular/cellular events that culminate in whole organ toxicity underpins development of novel safety assessment strategies. Current in vitro test systems are poorly predictive of toxicity of chemicals entering the systemic circulation, particularly to the liver. Such systems fall short because of 1) the physiological gap between cells currently used & human hepatocytes existing in their native state, 2) the lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity, 3) the inability to assess how low level cell damage induced by chemicals may develop into overt organ toxicity in a minority of patients, 4) lack of consideration of systemic effects. Reproduction of centrilobular & periportal hepatocyte phenotypes in in vitro culture is crucial for sensitive detection of cellular stress. Hepatocyte metabolism/phenotype is dependent on cell position along the liver lobule, with corresponding differences in exposure to substrate, oxygen & hormone gradients. Application of bioartificial liver (BAL) technology can encompass in vitro predictive toxicity testing with enhanced sensitivity and improved mechanistic understanding. Combining this technology with mechanistic mathematical models describing intracellular metabolism, fluid-­‐flow, substrate, hormone and nutrient distribution provides the opportunity to design the BAL specifically to mimic the in vivo scenario. Such mathematical models enable theoretical hypothesis testing, will inform the design of in vitro experiments, and will enable both refinement and reduction of in vivo animal trials. In this way, development of novel mathematical modelling tools will help to focus and direct in vitro and in vivo research, and can be used as a framework for other areas of drug safety science

Analysis of Hendra Virus Fusion Protein N-Terminal Transmembrane Residues

Hendra virus (HeV) is a zoonotic enveloped member of the family Paramyoxviridae. To successfully infect a host cell, HeV utilizes two surface glycoproteins: the attachment (G) protein to bind, and the trimeric fusion (F) protein to merge the viral envelope with the membrane of the host cell. The transmembrane (TM) region of HeV F has been shown to have roles in F protein stability and the overall trimeric association of F. Previously, alanine scanning mutagenesis has been performed on the C-terminal end of the protein, revealing the importance of β-branched residues in this region. Additionally, residues S490 and Y498 have been demonstrated to be important for F protein endocytosis, needed for the proteolytic processing of F required for fusion. To complete the analysis of the HeV F TM, we performed alanine scanning mutagenesis to explore the residues in the N-terminus of this region (residues 487–506). In addition to confirming the critical roles for S490 and Y498, we demonstrate that mutations at residues M491 and L492 alter F protein function, suggesting a role for these residues in the fusion process