Neighbourhood unemployment and other socio-demographic predictors of emergency hospitalisation for infectious intestinal disease in England: A longitudinal ecological study

BACKGROUND:Previous studies have observed that infectious intestinal disease (IID) related hospital admissions are higher in more deprived neighbourhoods. These studies have mainly focused on paediatric populations and are cross-sectional in nature. This study examines recent trends in emergency IID admission rates, and uses longitudinal methods to investigate the effects of unemployment (as a time varying measure of neighbourhood deprivation) and other socio-demographic characteristics on IID admissions for adults and children in England. METHODS:A longitudinal ecological analysis was performed using Hospital Episode Statistics on emergency hospitalisations for IID, collected over the time period 2012-17 across England. Analysis was conducted at the neighbourhood (Lower-layer Super Output Area) level for three age groups (0-14; 15-64; 65+ years). Mixed-effect Poisson regression models were used to assess the relationship between trends in neighbourhood unemployment and emergency IID admission rates, whilst controlling for measures of primary and secondary care access, underlying morbidity and the ethnic composition of each neighbourhood. RESULTS:From 2012-17, declining trends in emergency IID admission rates were observed for children and older adults overall, while rates increased for some sub-groups in the population. Each 1 percentage point increase in unemployment was associated with a 6.3, 2.4 and 4% increase in the rate of IID admissions per year for children [IRR=1.06, 95%CI 1.06-1.07], adults [IRR=1.02, 95%CI 1.02-1.03] and older adults [IRR=1.04, 95%CI 1.036-1.043], respectively. Increases in poor primary care access, the percentage of people from a Pakistani ethnic background, and the prevalence of long-term health problems, in a neighbourhood, were also associated with increases in IID admission rates. CONCLUSIONS:Increasing trends in neighbourhood deprivation, as measured by unemployment, were associated with increases in emergency IID admission rates for children and adults in England, despite controlling for measures of healthcare access, underlying morbidity and ethnicity. Research is needed to improve understanding of the mechanisms that explain these inequalities, so that effective policies can be developed to reduce the higher emergency IID admission rates experienced by more disadvantaged communities

Carbon isotope discrimination in leaves of the common paperbark tree, Melaleuca quinquenervia, as a tool for quantifying past tropical and subtropical rainfall

Quantitative reconstructions of terrestrial climate are highly sought after but rare, particularly in Australia. Carbon isotope discrimination in plant leaves (Δleaf) is an established indicator of past hydroclimate because the fractionation of carbon isotopes during photosynthesis is strongly influenced by water stress. Leaves of the evergreen tree Melaleuca quinquenervia have been recovered from the sediments of some perched lakes on North Stradbroke and Fraser Islands, south-east Queensland, eastern Australia. Here, we examine the potential for using M. quinquenervia ∆leaf as a tracer of past rainfall by analysing carbon isotope ratios (δ13C) of modern leaves. We firstly assess Δleaf variation at the leaf and stand scale and find no systematic pattern within leaves or between leaves due to their position on the tree. We then examine the relationships between climate and Δleaf for an 11 year timeseries of leaves collected in a litter tray. M. quinquenervia retains its leaves for 1-4 years; thus cumulative average climate data are used. There is a significant relationship between annual mean ∆leaf and mean annual rainfall of the hydrological year for 1-4 years (i.e. 365-1460 days) prior to leaf fall (r2=0.64, p=0.003, n=11). This relationship is marginally improved by accounting for the effect of pCO2 on discrimination (r2=0.67, p=0.002, n=11). The correlation between rainfall and Δleaf, and the natural distribution of Melaleuca quinquenervia around wetlands of eastern Australia, Papua New Guinea and New Caledonia offers significant potential to infer past rainfall on a wide range of spatial and temporal scales

The role of the chemokine receptor CXCR4 in infection with feline immunodeficiency virus

Infection with feline immunodeficiency virus (FIV) leads to the development of a disease state similar to AIDS in man. Recent studies have identified the chemokine receptor CXCR4 as the major receptor for cell culture-adapted strains of FIV, suggesting that FIV and human immunodeficiency virus (HIV) share a common mechanism of infection involving an interaction between the virus and a member of the seven transmembrane domain superfamily of molecules. This article reviews the evidence for the involvement of chemokine receptors in FIV infection and contrasts these findings with similar studies on the primate lentiviruses HIV and SIV (simian immunodeficiency virus)

Investigating the Influence of Ribavirin on Human Respiratory Syncytial Virus RNA Synthesis by Using a High-Resolution Transcriptome Sequencing Approach

Human respiratory syncytial virus (HRSV) is a major cause of serious respiratory tract infection. Treatment options include administration of ribavirin, a purine analog, although the mechanism of its anti-HRSV activity is unknown. We used transcriptome sequencing (RNA-seq) to investigate the genome mutation frequency and viral mRNA accumulation in HRSV-infected cells that were left untreated or treated with ribavirin. In the absence of ribavirin, HRSV-specific transcripts accounted for up to one-third of total RNA reads from the infected-cell RNA population. Ribavirin treatment resulted in a>90% reduction in abundance of viral mRNA reads, while at the same time no such reduction was detected for the abundance of cellular transcripts. The presented data reveal that ribavirin significantly increases the frequency of HRSV-specific RNA mutations, suggesting a direct influence on the fidelity of the HRSV polymerase. The presented data show that transitions and transversions occur during HRSV replication and that these changes occur in hot spots along the HRSV genome. Examination of nucleotide substitution rates in the viral genome indicated an increase in the frequency of transition but not transversion mutations in the presence of ribavirin. In addition, our data indicate that in the continuous cell types used and at the time points analyzed, the abundances of some HRSV mRNAs do not reflect the order in which the mRNAs are transcribed

Social patterning of telephone health-advice for diarrhoea and vomiting: analysis of 24 million telehealth calls in England.

OBJECTIVES:Gastrointestinal (GI) infections are common and most people do not see a physician. There is conflicting evidence of the impact of socioeconomic status (SES) on risk of GI infections. We assessed the relationship between SES and GI calls to two National Health Service (NHS) telephone advice services in England. METHODS:Over 24 million calls to NHS Direct (2010-13) and NHS 111 (2013-15) were extracted from Public Health England (PHE) syndromic surveillance systems. The relationship between SES and GI calls was assessed using generalised linear models (GLM). RESULTS:Adjusting for rurality and age-sex interactions, in NHS Direct, children in disadvantaged areas were at lower risk of GI calls; in NHS 111 there was a higher risk of GI calls in disadvantaged areas for all ages (0-4 years RR 1.27, 95% CI 1.25-1.29; 5-9 years RR 1.43, 95% CI 1.36-1.51; 10-14 years RR 1.36, 95% CI 1.26-1.41; 15-19 years RR 1.59, 95% CI 1.52-1.67; 20-59 years RR 1.50, 95% CI 1.47-1.53, 60 years and over RR 1.12, 95% CI 1.09-1.14). CONCLUSIONS:Disadvantaged areas had higher risk of GI calls in NHS 111. This may relate to differences in exposure or vulnerability to GI infections, or propensity to call about GI infections

Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma

Esophageal adenocarcinoma (EA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation, operating downstream of disease-associated exposures, is considered an important contributor to EA pathogenesis. Several risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), including symptomatic reflux, obesity, and smoking. The role of inherited genetic susceptibility remains an area of active investigation. To explore whether germline variation related to inflammatory processes influences susceptibility to BE/EA, we used data from a genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls. Our analysis included 7,863 single nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signaling, oxidative stress, human leukocyte antigen, and NFκB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. We identified a significant signal for the COX pathway in relation to BE risk (P=0.0059, FDR q=0.03), and in gene-level analyses found an association with MGST1 (microsomal glutathione-S-transferase 1; P=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Of these, four were subsequently confirmed (P<5.5 × 10−5) in a meta-analysis encompassing an independent set of 1,851 BE cases and 3,496 controls. Three of these SNPs (rs3852575, rs73112090, rs4149204) were associated with similar elevations in EA risk. This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/EA, and suggests that variants in MGST1 influence disease susceptibility