Reductions in cardiovascular, cerebrovascular, and respiratory mortality following the national Irish smoking ban: Interrupted time-series analysis

Copyright @ 2013 Stallings-Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality. Methods: A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results: Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76-0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63-0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54-0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46-0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35-64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32-0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305-4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking. Conclusions: The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in cerebrovascular and respiratory causes

Obstructive sleep apnoea in Type 2 diabetes mellitus: increased risk for overweight as well as obese people included in a national primary care database analysis

AIMS: To determine obstructive sleep apnoea prevalence in people with Type 2 or Type 1 diabetes in a national primary care setting, stratified by BMI category, and to explore the relationship between patient characteristics and obstructive sleep apnoea. METHODS: Using the Royal College of General Practitioners Research and Surveillance Centre database, a cross-sectional analysis was conducted. Diabetes type was identified using a seven-step algorithm and was grouped by Type 2 diabetes, Type 1 diabetes and no diabetes. The clinical characteristics of these groups were analysed, BMI-stratified obstructive sleep apnoea prevalence rates were calculated, and a multilevel logistic regression analysis was completed on the Type 2 diabetes group. RESULTS: Analysis of 1 275 461 adult records in the Royal College of General Practitioners Research and Surveillance Centre network showed that obstructive sleep apnoea was prevalent in 0.7%. In people with Type 2 diabetes, obstructive sleep apnoea prevalence increased with each increasing BMI category, from 0.5% in those of normal weight to 9.6% in those in the highest obesity class. By comparison, obstructive sleep apnoea prevalence rates for these BMI categories in Type 1 diabetes were 0.3% and 4.3%, and in those without diabetes 1.2% and 3.9%, respectively. Obstructive sleep apnoea was more prevalent in men than women in both diabetes types. When known risk factors were adjusted for, there were increased odds ratios for obstructive sleep apnoea in people with Type 2 diabetes in the overweight and higher BMI categories. CONCLUSIONS: Obstructive sleep apnoea was reported in people with both types of diabetes across the range of overweight categories and not simply in the highest obesity class

Discovery and characterization of chromatin states for systematic annotation of the human genome

A plethora of epigenetic modifications have been described in the human genome and shown to play diverse roles in gene regulation, cellular differentiation and the onset of disease. Although individual modifications have been linked to the activity levels of various genetic functional elements, their combinatorial patterns are still unresolved and their potential for systematic de novo genome annotation remains untapped. Here, we use a multivariate Hidden Markov Model to reveal 'chromatin states' in human T cells, based on recurrent and spatially coherent combinations of chromatin marks. We define 51 distinct chromatin states, including promoter-associated, transcription-associated, active intergenic, large-scale repressed and repeat-associated states. Each chromatin state shows specific enrichments in functional annotations, sequence motifs and specific experimentally observed characteristics, suggesting distinct biological roles. This approach provides a complementary functional annotation of the human genome that reveals the genome-wide locations of diverse classes of epigenetic function.National Science Foundation (U.S.). (Award 0905968)National Human Genome Research Institute (U.S.) (Award U54-HG004570)National Human Genome Research Institute (U.S.) (Award RC1-HG005334

Production properties of K*(892) vector mesons and their spin alignment as measured in the NOMAD experiment

First measurements of K*(892) mesons production properties and their spin alignment in nu_mu charged current (CC) and neutral current (NC) interactions are presented. The analysis of the full data sample of the NOMAD experiment is performed in different kinematic regions. For K*+ and K*- mesons produced in nu_mu CC interactions and decaying into K0 pi+/- we have found the following yields per event: (2.6 +/- 0.2 (stat.) +/- 0.2 (syst.))% and (1.6 +/- 0.1 (stat.) +/- 0.1 (syst.))% respectively, while for the K*+ and K*- mesons produced in nu NC interactions the corresponding yields per event are: (2.5 +/- 0.3 (stat.) +/- 0.3 (syst.))% and (1.0 +/- 0.3 (stat.) +/- 0.2 (syst.))%. The results obtained for the rho00 parameter, 0.40 +/- 0.06 (stat) +/- 0.03 (syst) and 0.28 +/- 0.07 (stat) +/- 0.03 (syst) for K*+ and K*- produced in nu_mu CC interactions, are compared to theoretical predictions tuned on LEP measurements in e+e- annihilation at the Z0 pole. For K*+ mesons produced in nu NC interactions the measured rho00 parameter is 0.66 +/- 0.10 (stat) +/- 0.05 (syst).Comment: 20 p

Too close for comfort: spatial patterns in acorn barnacle populations

Spatial patterns in aggregations form as a result of the interplay between costs and benefits experienced by individuals. Such self-organisation of aggregations can be explained using a zonal model in which a short-range zone of repulsion and longer-range zone of attraction surrounding individuals leads to emergent pattern properties. The signal of these processes can be detected using spatial pattern analyses. Furthermore, in sessile organisms, post-settlement mortality reveals the relative costs and benefits of positions within the aggregation. Acorn barnacles are known to require contact with conspecifics for reproduction and are therefore believed to aggregate for this purpose; isolated individuals may also be more susceptible to abiotic stress and predation. At short distances, however, competition for space and resources is likely to occur. In this study spatial patterns of barnacles (Semibalanus balanoides L.) were analysed using pair-correlation functions. Individuals were dispersed at distances below 0.30 cm, but peak relative density occurred at a distance of 0.36 cm from conspecifics. This is much closer than required for reproductive access, implying a strong aggregative drive, up to the point of physical contact with neighbours. Nevertheless, analysis of dead barnacles illustrated that such proximity carries a cost as barnacles with many neighbours were more likely to have died. The inferences obtained from these patterns are that barnacles aggregate as closely as they can, and that local neighbourhood competition is a powerful determinant of mortality. These processes give rise to the observed pattern properties

Influence of emphysema distribution on pulmonary function parameters in COPD patients

Objective: To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD. Methods: The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings. We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD. We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD). Results: Eighty-six patients were included. The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years). The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%. Type 2 emphysema distribution was associated with lower FEV1 , FVC, FEV1 /FVC ratio, and DLCO. In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003). The type 3 patients had a higher RV/TLC ratio, although the difference was not significant. Conclusions: The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation. The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans

DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 � 10?6). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability

The effects of integrated care: a systematic review of UK and international evidence

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725

Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19–recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19–recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19–uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2–specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2–specific antibody responses and has implications for long-term protection from COVID-19