The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation:A case-crossover analysis

In bronchiectasis, exacerbations are believed to be triggered by infectious agents, but often no pathogen can be identified. We hypothesised that acute air pollution exposure may be associated with bronchiectasis exacerbations.We combined a case-crossover design with distributed lag models in an observational record linkage study. Patients were recruited from a specialist bronchiectasis clinic at Ninewells Hospital, Dundee, UK.We recruited 432 patients with clinically confirmed bronchiectasis, as diagnosed by high-resolution computed tomography. After excluding days with missing air pollution data, the final model for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM; 10; ) was based on 6741 exacerbations from 430 patients and for nitrogen dioxide (NO; 2; ) it included 6248 exacerbations from 426 patients. For each 10 µg·m; -; ³ increase in PM; 10; and NO; 2; , the risk of having an exacerbation that same day increased significantly by 4.5% (95% CI 0.9-8.3) and 3.2% (95% CI 0.7-5.8) respectively. The overall (lag zero to four) increase in risk of exacerbation for a 10 μg·m; -3; increase in air pollutant concentration was 11.2% (95% CI 6.0-16.8) for PM; 10; and 4.7% (95% CI 0.1-9.5) for NO; 2; Subanalysis showed higher relative risks during spring (PM; 10; 1.198 (95% CI 1.102-1.303), NO; 2; 1.146 (95% CI 1.035-1.268)) and summer (PM; 10; 2.142 (95% CI 1.785-2.570), NO; 2; 1.352 (95% CI 1.140-1.602)) when outdoor air pollution exposure would be expected to be highest.In conclusion, acute air pollution fluctuations are associated with increased exacerbation risk in bronchiectasis

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Transport mode choice and body mass index: Cross-sectional and longitudinal evidence from a European-wide study.

BACKGROUND: In the fight against rising overweight and obesity levels, and unhealthy urban environments, the renaissance of active mobility (cycling and walking as a transport mode) is encouraging. Transport mode has been shown to be associated to body mass index (BMI), yet there is limited longitudinal evidence demonstrating causality. We aimed to associate transport mode and BMI cross-sectionally, but also prospectively in the first ever European-wide longitudinal study on transport and health. METHODS: Data were from the PASTA project that recruited adults in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich) to complete a series of questionnaires on travel behavior, physical activity levels, and BMI. To assess the association between transport mode and BMI as well as change in BMI we performed crude and adjusted linear mixed-effects modeling for cross-sectional (n = 7380) and longitudinal (n = 2316) data, respectively. RESULTS: Cross-sectionally, BMI was 0.027 kg/m2 (95%CI 0.015 to 0.040) higher per additional day of car use per month. Inversely, BMI was -0.010 kg/m2 (95%CI -0.020 to -0.0002) lower per additional day of cycling per month. Changes in BMI were smaller in the longitudinal within-person assessment, however still statistically significant. BMI decreased in occasional (less than once per week) and non-cyclists who increased cycling (-0.303 kg/m2, 95%CI -0.530 to -0.077), while frequent (at least once per week) cyclists who stopped cycling increased their BMI (0.417 kg/m2, 95%CI 0.033 to 0.802). CONCLUSIONS: Our analyses showed that people lower their BMI when starting or increasing cycling, demonstrating the health benefits of active mobility

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Traffic Air Pollution and Oxidized LDL

BACKGROUND: Epidemiologic studies indirectly suggest that air pollution accelerates atherosclerosis. We hypothesized that individual exposure to particulate matter (PM) derived from fossil fuel would correlate with plasma concentrations of oxidized low-density lipoprotein (LDL), taken as a marker of atherosclerosis. We tested this hypothesis in patients with diabetes, who are at high risk for atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study of non-smoking adult outpatients with diabetes we assessed individual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputum induction and by determining the distance from the patient's residence to a major road, through geocoding. These exposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogen activator inhibitor 1 (PAI-1). We could assess the carbon load of airway macrophages in 79 subjects (58 percent). Each doubling in the distance of residence from major roads was associated with a 0.027 µm(2) decrease (95% confidence interval (CI): -0.048 to -0.0051) in the carbon load of airway macrophages. Independently from other covariates, we found that each increase of 0.25 µm(2) [interquartile range (IQR)] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3 to 13.3) in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of -2.9 U/L (95% CI: -5.2 to -0.72) in oxidized LDL. Neither the carbon load of macrophages nor the distance from residence to major roads, were associated with plasma von Willebrand factor or PAI-1. CONCLUSIONS: The observed positive association, in a susceptible group of the general population, between plasma oxidized LDL levels and either the carbon load of airway macrophages or the proximity of the subject's residence to busy roads suggests a proatherogenic effect of traffic air pollution

Aberrant iPSC-derived human astrocytes in Alzheimer's disease

The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically-defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs). All astrocytes expressed functional markers including; glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 1 (EAAT1), S100B and glutamine synthetase (GS) comparable to that of adult astrocytes in vivo. However, induced astrocytes derived from both SAD and FAD patients exhibit a pronounced pathological phenotype, with a significantly less complex morphological appearance, overall atrophic profiles, and abnormal localisation of key functional astroglial markers. Furthermore, NPCs derived from identical patients did not show any differences, therefore, validating that remodelled astroglia are not as a result of defective neuronal intermediates. This work not only presents a novel model to study the mechanisms of human astrocytes in vitro, but also provides an ideal platform for further interrogation of early astroglial cell-autonomous events in AD and the possibility of identification of novel therapeutic targets for the treatment of AD

Short Telomeres in Hatchling Snakes: Erythrocyte Telomere Dynamics and Longevity in Tropical Pythons

Telomere length (TL) has been found to be associated with life span in birds and humans. However, other studies have demonstrated that TL does not affect survival among old humans. Furthermore, replicative senescence has been shown to be induced by changes in the protected status of the telomeres rather than the loss of TL. In the present study we explore whether age- and sex-specific telomere dynamics affect life span in a long-lived snake, the water python (Liasis fuscus)

First observation of Bs -> D_{s2}^{*+} X mu nu decays

Using data collected with the LHCb detector in proton-proton collisions at a centre-of-mass energy of 7 TeV, the semileptonic decays Bs -> Ds+ X mu nu and Bs -> D0 K+ X mu nu are detected. Two structures are observed in the D0 K+ mass spectrum at masses consistent with the known D^+_{s1}(2536) and $D^{*+}_{s2}(2573) mesons. The measured branching fractions relative to the total Bs semileptonic rate are B(Bs -> D_{s2}^{*+} X mu nu)/B(Bs -> X mu nu)= (3.3\pm 1.0\pm 0.4)%, and B(Bs -> D_{s1}^+ X munu)/B(Bs -> X mu nu)= (5.4\pm 1.2\pm 0.5)%, where the first uncertainty is statistical and the second is systematic. This is the first observation of the D_{s2}^{*+} state in Bs decays; we also measure its mass and width.Comment: 8 pages 2 figures. Published in Physics Letters

Kernel bandwidth optimization in spike rate estimation

Kernel smoother and a time-histogram are classical tools for estimating an instantaneous rate of spike occurrences. We recently established a method for selecting the bin width of the time-histogram, based on the principle of minimizing the mean integrated square error (MISE) between the estimated rate and unknown underlying rate. Here we apply the same optimization principle to the kernel density estimation in selecting the width or “bandwidth” of the kernel, and further extend the algorithm to allow a variable bandwidth, in conformity with data. The variable kernel has the potential to accurately grasp non-stationary phenomena, such as abrupt changes in the firing rate, which we often encounter in neuroscience. In order to avoid possible overfitting that may take place due to excessive freedom, we introduced a stiffness constant for bandwidth variability. Our method automatically adjusts the stiffness constant, thereby adapting to the entire set of spike data. It is revealed that the classical kernel smoother may exhibit goodness-of-fit comparable to, or even better than, that of modern sophisticated rate estimation methods, provided that the bandwidth is selected properly for a given set of spike data, according to the optimization methods presented here

Influence of mercury exposure on blood pressure, resting heart rate and heart rate variability in French Polynesians: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Populations which diet is rich in seafood are highly exposed to contaminants such as mercury, which could affect cardiovascular risk factors</p> <p>Objective</p> <p>To assess the associations between mercury and blood pressure (BP), resting heart rate (HR) and HR variability (HRV) among French Polynesians</p> <p>Methods</p> <p>Data were collected among 180 adults (≥ 18 years) and 101 teenagers (12-17 years). HRV was measured using a two-hour ambulatory electrocardiogram (Holter) and BP was measured using a standardized protocol. The association between mercury and HRV and BP parameters was studied using analysis of variance (ANOVA) and analysis of covariance (ANCOVA)</p> <p>Results</p> <p>Among teenagers, the high frequency (HF) decreased between the 2^ndand 3^rdtertile (380 vs. 204 ms², p = 0.03) and a similar pattern was observed for the square root of the mean squared differences of successive R-R intervals (rMSSD) (43 vs. 30 ms, p = 0.005) after adjusting for confounders. In addition, the ratio low/high frequency (LF/HF) increased between the 2^ndand 3^rdtertile (2.3 vs. 3.0, p = 0.04). Among adults, the standard deviation of R-R intervals (SDNN) tended to decrease between the 1^stand 2^ndtertile (84 vs. 75 ms, p = 0.069) after adjusting for confounders. Furthermore, diastolic BP tended to increase between the 2^ndand 3^rdtertile (86 vs. 91 mm Hg, p = 0.09). No significant difference was observed in resting HR or pulse pressure (PP)</p> <p>Conclusions</p> <p>Mercury was associated with decreased HRV among French Polynesian teenagers while no significant association was observed with resting HR, BP, or PP among teenagers or adults</p