Mixtures of long-term exposure to ambient air pollution, built environment and temperature and stroke incidence across Europe

Introduction: The complex interplay of multiple environmental factors and cardiovascular has scarcely been studied. Within the EXPANSE project, we evaluated the association between long-term exposure to multiple environmental indices and stroke incidence across Europe. Methods: Participants from three traditional adult cohorts (Germany, Netherlands and Sweden) and four administrative cohorts (Catalonia [region Spain], Rome [city-wide], Greece and Sweden [nationwide]) were followed until incident stroke, death, migration, loss of follow-up or study end. We estimated exposures at residential addresses from different exposure domains: air pollution (nitrogen dioxide (NO2), particulate matter < 2.5 μm (PM2.5), black carbon (BC), ozone), built environment (green/blue spaces, impervious surfaces) and meteorology (seasonal mean and standard deviation of temperatures). Associations between environmental exposures and stroke were estimated in single and multiple-exposure Cox proportional hazard models, and Principal Component (PC) Analyses derived prototypes for specific exposures domains. We carried out random effects meta-analyses by cohort type. Results: In over 15 million participants, increased levels of NO2 and BC were associated with increased higher stroke incidence in both cohort types. Increased Normalized Difference Vegetation Index (NDVI) was associated with a lower stroke incidence in both cohort types, whereas an increase in impervious surface was associated with an increase in stroke incidence. The first PC of the air pollution domain (PM2.5, NO2 and BC) was associated with an increase in stroke incidence. For the built environment, higher levels of NDVI and lower levels of impervious surfaces were associated with a protective effect [%change in HR per 1 unit = −2.0 (95 %CI, −5.9;2.0) and −1.1(95 %CI, −2.0; −0.3) for traditional adult and administrative cohorts, respectively]. No clear patterns were observed for distance to blue spaces or temperature parameters. Conclusions: We observed increased HRs for stroke with exposure to PM2.5, NO2 and BC, lower levels of greenness and higher impervious surface in single and combined exposure models

Air pollution: metabolites and respiratory health across the life-course

Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data

Disentangling associations between multiple environmental exposures and all-cause mortality: an analysis of European administrative and traditional cohorts

BACKGROUND: We evaluated the independent and joint effects of air pollution, land/built environment characteristics, and ambient temperature on all-cause mortality as part of the EXPANSE project. METHODS: We collected data from six administrative cohorts covering Catalonia, Greece, the Netherlands, Rome, Sweden, and Switzerland and three traditional cohorts in Sweden, the Netherlands, and Germany. Participants were linked to spatial exposure estimates derived from hybrid land use regression models and satellite data for: air pollution [fine particulate matter (PM 2.5), nitrogen dioxide (NO₂), black carbon (BC), warm season ozone (O 3)], land/built environment [normalized difference vegetation index (NDVI), distance to water, impervious surfaces], and ambient temperature (the mean and standard deviation of warm and cool season temperature). We applied Cox proportional hazard models accounting for several cohort-specific individual and area-level variables. We evaluated the associations through single and multiexposure models, and interactions between exposures. The joint effects were estimated using the cumulative risk index (CRI). Cohort-specific hazard ratios (HR) were combined using random-effects meta-analyses. RESULTS: We observed over 3.1 million deaths out of approximately 204 million person-years. In administrative cohorts, increased exposure to PM 2.5, NO 2, and BC was significantly associated with all-cause mortality (pooled HRs: 1.054, 1.033, and 1.032, respectively). We observed an adverse effect of increased impervious surface and mean season-specific temperature, and a protective effect of increased O 3, NDVI, distance to water, and temperature variation on all-cause mortality. The effects of PM 2.5 were higher in areas with lower (10th percentile) compared to higher (90th percentile) NDVI levels [pooled HRs: 1.054 (95% confidence interval (CI) 1.030-1.079) vs. 1.038 (95% CI 0.964-1.118)]. A similar pattern was observed for NO 2. The CRI of air pollutants (PM 2.5 or NO 2) plus NDVI and mean warm season temperature resulted in a stronger effect compared to single-exposure HRs: [PM 2.5 pooled HR: 1.061 (95% CI 1.021-1.102); NO 2 pooled HR: 1.041 (95% CI 1.025-1.057)]. Non-significant effects of similar patterns were observed in traditional cohorts. DISCUSSION: The findings of our study not only support the independent effects of long-term exposure to air pollution and greenness, but also highlight the increased effect when interplaying with other environmental exposures

Belgian and Dutch Jihadist Foreign Fighters (2012–2015): Characteristics, Motivations, and Roles in the War in Syria and Iraq

In recent years, Belgium and the Netherlands have been confronted with relatively many citizens or residents who have traveled to Syria and Iraq to join and fight with jihadist groups — 388 Belgian and 220 Dutch as estimated by the respective authorities. This article provides an overview of the phenomenon of jihadist foreign fighters in the Low Countries, analyzing their characteristics, motivations, and roles in the war in Syria and Iraq. It compares the Belgian and Dutch cases, focusing on key aspects, such as age, sex, and geographical and socioeconomic background.Security and Global Affair

Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis

The objective of this study was to identify differentially expressed and prognostically important genes in pediatric medulloblastoma and pediatric ependymoma by Affymetrix microarray analysis. Among the most discriminative genes, three members of the SOX transcription factor family were differentially expressed. Both SOX4 and SOX11 were significantly overexpressed in medulloblastoma (median, 11-fold and 5-fold, respectively) compared with ependymoma and normal cerebellum. SOX9 had greater expression in ependymoma (median, 16-fold) compared with normal cerebellum and medulloblastoma (p < 0.001 for all comparisons). The differential expression of the SOX genes was confirmed at the protein level by immunohistochemical analysis. Survival analysis of the most discriminative probe sets for each subgroup showed that 35 and 13 probe sets were predictive of survival in patients with medulloblastoma and ependymoma, respectively. There was a trend toward better survival with increasing SOX4 expression in medulloblastoma. SOX9 expression was predictive for favorable outcome in ependymoma. The mRNA levels of BCAT1, a mediator of amino acid breakdown, were higher (median, 15-fold) in medulloblastoma patients with metastases compared with those without metastasized disease (p < 0.01). However, the correlation between BCAT1 expression and metastatic medulloblastoma could not be confirmed at the protein level. The potential prognostic effect of the genes associated with outcome should be evaluated in ongoing studies using larger groups of patients. Furthermore, our findings support further analysis of the functional properties of the selected genes, especially SOX4 and BCAT1 for medulloblastoma and SOX9 for ependymoma, to evaluate the use of these genes as potential tumor markers, prognostic markers, and drug targets in pediatric brain tumors

Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis

The aim of this study was to identify aberrantly expressed proteins in pediatric primitive neuroectodermal tumors (PNETs) and ependymornas. Tumor tissue of 29 PNET and 12 ependymoma patients was subjected to 2-dimensional difference gel electrophoresis. Gel analysis resulted in 79 protein spots being differentially expressed between PNETs and ependymomas (p <0.0 1, fold change difference in expression > 2). Three proteins, stathmin, annexin At, and calcyphosine, were chosen for validation by immunohistochemistry. Stathmin was expressed 2.6-fold higher in PNETs than in ependymomas, and annexin A1 and calcyphosine were expressed 2.5- and 37.6-fold higher, respectively, in ependymomas. All PNETs showed strong staining for stathmin, and all ependymomas were strongly positive for annexin A1, whereas control tissues were negative. Calcyphosine immunoreactivity was observed in 59% of the ependymomas and was most profound in ependymoma tissue showing epithelial differentiation. mRNA expression levels of stathmin, annexin A1, and calcyphosine significantly correlated (R-s = 0.65 [p <0.0001], R-s = 0.50 [p = 0.001], and R, = 0.72 [p <0.0001], respectively) with protein expression levels. In conclusion, using a protcome-wide approach, stathmin, annexin At, and calcyphosine were successfully identified as tumor-specific proteins in pediatric PNETs and ependymornas. Ongoing studies are focused on characterizing the role of these proteins as tumor markers and potential drug targets in pediatric brain tumors