Exposure to air pollution near a steel plant is associated with reduced heart rate variability: a randomised crossover study

Abstract Background Epidemiological studies have shown that as ambient air pollution (AP) increases the risk of cardiovascular mortality also increases. The mechanisms of this effect may be linked to alterations in autonomic nervous system function. We wished to examine the effects of industrial AP on heart rate variability (HRV), a measure of subtle changes in heart rate and rhythm representing autonomic input to the heart. Methods Sixty healthy adults were randomized to spend five consecutive 8-h days outdoors in one of two locations: (1) adjacent to a steel plant in the Bayview neighbourhood in Sault Ste Marie Ontario or (2) at a College campus, several kilometers from the plant. Following a 9\u201316 day washout period, participants spent five consecutive days at the other site. Ambient AP levels and ambulatory electrocardiogram recordings were collected daily. HRV analysis was undertaken on a segment of the ambulatory ECG recording during a 15\ua0min rest period, near the end of the 8-h on-site day. Standard HRV parameters from both time and frequency domains were measured. Ambient AP was measured with fixed site monitors at both sites. Statistical analysis was completed using mixed-effects models. Results Compared to the College site, HRV was statistically significantly reduced at the Bayview site by 13% (95%CI 3.6,19.2) for the standard deviation of normal to normal, 8% (95%CI 0.1, 4.9) for the percent normal to normal intervals differing by more than 50 ms, and 15% (95%CI 74.9, 571.2) for low frequency power. Levels of carbon monoxide, sulphur dioxide, nitrogen dioxide, and fine and ultrafine particulates were slightly, but statistically significantly, elevated at Bayview when compared to College. Interquartile range changes in individual air pollutants were significantly associated with reductions in HRV measured on the same day. The patterns of effect showed a high degree of consistency, with nearly all pollutants significantly inversely associated with at least one measure of HRV. Conclusions The significant associations between AP and changes in HRV suggest that ambient AP near a steel plant may impact autonomic nervous system control of the heart

How does playing adapted sports affect quality of life of people with mobility limitations? Results from a mixed-method sequential explanatory study

Abstract Background Occupations, including physical activity, are a strong determinant of health. However, mobility limitations can restrict opportunities to perform these occupations, which may affect quality of life. Some people will turn to adapted sports to meet their need to be involved in occupations. Little is known, however, about how participation in adapted sports affects the quality of life of people with mobility limitations. This study thus aimed to explore the influence of adapted sports on quality of life in adult wheelchair users. Methods A mixed-method sequential explanatory design was used, including a quantitative and a qualitative component with a clinical research design. A total of 34 wheelchair users aged 18 to 62, who regularly played adapted sports, completed the Quality of Life Index (/30). Their scores were compared to those obtained by people of similar age without limitations (general population). Ten of the wheelchair users also participated in individual semi-structured interviews exploring their perceptions regarding how sports-related experiences affected their quality of life. Results The participants were 9 women and 25 men with paraplegia, the majority of whom worked and played an individual adapted sport (athletics, tennis or rugby) at the international or national level. People with mobility limitations who participated in adapted sports had a quality of life comparable to the group without limitations (21.9\u2009\ub1\u20093.3 vs 22.3\u2009\ub1\u20092.9 respectively), except for poorer family-related quality of life (21.0\u2009\ub1\u20095.3 vs 24.1\u2009\ub1\u20094.9 respectively). Based on the interviews, participants reported that the positive effect of adapted sports on the quality of life of people with mobility limitations operates mainly through the following: personal factors (behavior-related abilities and health), social participation (in general and through interpersonal relationships), and environmental factors (society\u2019s perceptions and support from the environment). Some contextual factors, such as resources and the accessibility of organizations and training facilities, are important and contributed indirectly to quality of life. Negative aspects, such as performance-related stress and injury, also have an effect. Conclusions People with mobility limitations playing adapted sports and people without limitations have a ..

Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution

Abstract We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking

3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets

Abstract Many mutations in cancer are of unknown functional significance. Standard methods use statistically significant recurrence of mutations in tumor samples as an indicator of functional impact. We extend such analyses into the long tail of rare mutations by considering recurrence of mutations in clusters of spatially close residues in protein structures. Analyzing 10,000 tumor exomes, we identify more than 3000 rarely mutated residues in proteins as potentially functional and experimentally validate several in RAC1 and MAP2K1. These potential driver mutations (web resources: 3dhotspots.org and cBioPortal.org) can extend the scope of genomically informed clinical trials and of personalized choice of therapy

Whole genome sequencing reveals high-resolution epidemiological links between clinical and environmental Klebsiella pneumoniae

Abstract Background Klebsiella pneumoniae is a gram-negative bacterial species capable of occupying a broad range of environmental and clinical habitats. Known as an opportunistic pathogen, it has recently become a major causative agent of clinical infections worldwide. Despite growing knowledge about the highly diverse population of K. pneumoniae , the evolution and clinical significance of environmental K. pneumoniae , as well as the relationship between clinical and environmental K. pneumoniae , are poorly defined. Methods We isolated and sequenced K. pneumoniae from in-patients in a single hospital in Thailand, as well as hospital sewage, and surrounding canals and farms within a 20-km radius. Results Phylogenetic analysis of 77\u2009 K. pneumoniae (48 clinical and 29 non-clinical isolates) demonstrated that the two groups were intermixed throughout the tree and in some cases resided in the same clade, suggesting recent divergence from a common ancestor. Phylogenetic comparison of the 77 Thai genomes with 286\u2009 K. pneumoniae from a global collection showed that Thai isolates were closely related to the clinical sub-population of the global collection, indicating that Thai clinical isolates belonged to globally circulating lineages. Dating of four Thai K. pneumoniae clades indicated that they emerged between 50 and 150\ua0years ago. Despite their phylogenetic relatedness, virulence factors and \u3b2-lactamase resistance genes were more numerous in clinical than in environmental isolates. Our results indicate that clinical and environmental K. pneumoniae are closely related, but that hospitals may select for isolates with a more resistant and virulent genotype. Conclusions These findings highlight the clinical relevance of environmental K. pneumoniae isolates

Combining omics data to identify genes associated with allergic rhinitis

Abstract Allergic rhinitis is a common chronic disorder characterized by immunoglobulin E-mediated inflammation. To identify new genes associated with this trait, we performed genome- and epigenome-wide association studies and linked marginally significant CpGs located in genes or its promoter and SNPs located 1\ua0Mb from the CpGs, by identifying cis methylation quantitative trait loci (mQTL). This approach relies on functional cellular aspects rather than stringent statistical correction. We were able to identify one gene with significant cis -mQTL for allergic rhinitis, caudal-type homeobox 1 ( CDX1 ). We also identified 11 genes with marginally significant cis -mQTLs ( p \u2009<\u20090.05) including one with both allergic rhinitis with or without asthma ( RNF39 ). Moreover, most SNPs identified were not located closest to the gene they were linked to through cis -mQTLs counting the one linked to CDX1 located in a gene previously associated with asthma and atopic dermatitis. By combining omics data, we were able to identify new genes associated with allergic rhinitis and better assess the genes linked to associated SNPs

Is health care a necessary or luxury product for Asian countries? An answer using panel approach

Abstract A number of studies have estimated the income elasticity of health care expenditure to identify whether health care is a necessary or luxury product. However, the issue has received less attention in developing countries, especially in Asian economies. The current study for the first time has used the panel data covering 36 Asian countries for the period 1995\u20132013 for revealing the nature of health care as a product. Along with conventional econometric techniques we have addressed the issue of cross section dependence and used Westerlund (2007) panel cointegration test which is robust against cross section dependence and heterogeneity for detecting the presence of panel cointegration. By applying Fully Modified OLS (FMOLS) and Dynamic OLS (DOLS) it was found that the long run elasticity of Health Care Expenditure (HCE) with Gross Domestic Product (GDP) is less than unit implying that the health care can be regarded as necessary in nature for these countries. JEL Classification: I10, C51

Native flexibility of structurally homologous proteins: insights from anisotropic network model

Abstract Background Single-molecule microscopic experiments can measure the mechanical response of proteins to pulling forces applied externally along different directions (inducing different residue pairs in the proteins by uniaxial tension). This response to external forces away from equilibrium should in principle, correlate with the flexibility or stiffness of proteins in their folded states. Here, a simple topology-based atomistic anisotropic network model (ANM) is shown which captures the protein flexibility as a fundamental property that determines the collective dynamics and hence, the protein conformations in native state. Methods An all-atom ANM is used to define two measures of protein flexibility in the native state. One measure quantifies overall stiffness of the protein and the other one quantifies protein stiffness along a particular direction which is effectively the mechanical resistance of the protein towards external pulling force exerted along that direction. These measures are sensitive to the protein sequence and yields reliable values through computations of normal modes of the protein. Results ANM at an atomistic level (heavy atoms) explains the experimental (atomic force microscopy) observations viz., different mechanical stability of structurally similar but sequentially distinct proteins which, otherwise were implied to possess similar mechanical properties from analytical/theoretical coarse-grained (backbone only) models. The results are exclusively demonstrated for human fibronectin (FN) protein domains. Conclusions The topology of interatomic contacts in the folded states of proteins essentially determines the native flexibility. The mechanical differences of topologically similar proteins are captured from a high-resolution (atomic level) ANM at a low computational cost. The relative trend in flexibility of such proteins is reflected in their stability differences that they exhibit while unfolding in atomic force microscopic (AFM) experiments

The extinction and persistence of a stochastic SIR model

Abstract The objective of this paper is to explore the long time behavior of a stochastic SIR model. We establish a threshold condition called the basic reproduction number under stochastic perturbation for persistence or extinction of the disease. Especially, some numerical simulations are applied to support our theoretical results. MSC: 49K15, 60H10, 93E15

Livestock ownership, animal source foods and child nutritional outcomes in seven rural village clusters in Sub-Saharan Africa

Abstract Background Sub-Saharan Africa currently has the highest prevalence of malnutrition worldwide. In children under the age of 5\ua0years, malnutrition can have long-term effects on physical and cognitive development, with implications at the national scale. Theoretically, livestock-based interventions are well placed to overcome constraints faced by micronutrient and/or food-based interventions. However, there is limited empirical evidence to support this hypothesis. Methods This study utilised agriculture, nutrition and anthropometry data from the Millennium Villages Project to investigate relationships between livestock ownership, animal source foods (ASF) consumption and child nutritional outcomes across seven rural village clusters in Sub-Saharan Africa. Village clusters were located in different agro-ecological zones and included: Bonsaaso, Ghana; Mayange, Rwanda; Mwandama, Malawi; Tiby, Mali; Pampaida, Nigeria; Potou, Senegal; and Ruhiira, Uganda. Data from 1624 households (including 1543 children) were included in the analysis. Results Overall, the proportion of children with stunting, underweight or wasting across the seven village clusters was 40, 18 and 5%, respectively. Livestock ownership, ASF consumption and child nutritional outcomes varied between village clusters. Households that owned livestock were generally more likely to consume associated ASF. For example, the proportion of households that consumed milk was higher in households that owned cows compared to those that did not in Pampaida, Mayange and Ruhiira ( P \ua0<\ua00.05), while poultry meat consumption was generally higher in poultry-keeping households in Mayange and Ruhiira ( P \ua0<\ua00.05). The relationship between ASF consumption and anthropometric measurements was complex, ranging from positively to negatively associated depending on the food commodity and village cluster. For instance, in Ruhiira, the mean weight-for-age Z score\ua0(WAZ) was significantly higher (better) in children from households that consumed eggs in the last 30\ua0days, while in Potou, mean WAZ was significantly lower (worse) in children from households that consumed eggs in the last 30\ua0days ( P \ua0<\ua00.05). Conclusions This study contributes to the growing body of research that investigates the relationships between livestock ownership, ASF consumption and nutritional outcomes in children. Our results reveal complex patterns that vary across agro-ecological zones. More research is needed to assess seasonal variations in these factors, effects of gender roles on intra-household ..