Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude.

BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N). CONCLUSIONS: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.

The impact of black carbon (BC) on mode-specific galvanic skin response (GSR) as a measure of stress in urban environments.

Previous research has shown that walking and cycling could help alleviate stress in cities, however there is poor knowledge on how specific microenvironmental conditions encountered during daily journeys may lead to varying degrees of stress experienced at that moment. We use objectively measured data and a robust causal inference framework to address this gap. Using a Bayesian Doubly Robust (BDR) approach, we find that black carbon exposure statistically significantly increases stress, as measured by Galvanic Skin Response (GSR), while cycling and while walking. Augmented Outcome Regression (AOR) models indicate that greenspace exposure and the presence of walking or cycling infrastructure could reduce stress. None of these effects are statistically significant for people in motorized transport. These findings add to a growing evidence-base on health benefits of policies aimed at decreasing air pollution, improving active travel infrastructure and increasing greenspace in cities.

Day-to-day intrapersonal variability in mobility patterns and association with perceived stress: A cross-sectional study using GPS from 122 individuals in three European cities.

Many aspects of our life are related to our mobility patterns and individuals can exhibit strong tendencies towards routine in their daily lives. Intrapersonal day-to-day variability in mobility patterns has been associated with mental health outcomes. The study aims were: (a) calculate intrapersonal day-to-day variability in mobility metrics for three cities; (b) explore interpersonal variability in mobility metrics by sex, season and city, and (c) describe intrapersonal variability in mobility and their association with perceived stress. Data came from the Physical Activity through Sustainable Transport Approaches (PASTA) project, 122 eligible adults wore location measurement devices over 7-consecutive days, on three occasions during 2015 (Antwerp: 41, Barcelona: 41, London: 40). Participants completed the Short Form Perceived Stress Scale (PSS-4). Day-to-day variability in mobility was explored via six mobility metrics using distance of GPS point from home (meters:m), distance travelled between consecutive GPS points (m) and energy expenditure (metabolic equivalents:METs) of each GPS point collected (n = 3,372,919). A Kruskal-Wallis H test determined whether the median daily mobility metrics differed by city, sex and season. Variance in correlation quantified day-to-day intrapersonal variability in mobility. Levene's tests or Kruskal-Wallis tests were applied to assess intrapersonal variability in mobility and perceived stress. There were differences in daily distance travelled, maximum distance from home and METS between individuals by sex, season and, for proportion of time at home also, by city. Intrapersonal variability across all mobility metrics were highly correlated; individuals had daily routines and largely stuck to them. We did not observe any association between stress and mobility. Individuals are habitual in their daily mobility patterns. This is useful for estimating environmental exposures and in fuelling simulation studies.

Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies Participants.

Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

The effects of traveling in different transport modes on galvanic skin response (GSR) as a measure of stress: An observational study.

BACKGROUND: Stress is one of many ailments associated with urban living, with daily travel a potential major source. Active travel, nevertheless, has been associated with lower levels of stress compared to other modes. Earlier work has relied on self-reported measures of stress, and on study designs that limit our ability to establish causation. OBJECTIVES: To evaluate effects of daily travel in different modes on an objective proxy measure of stress, the galvanic skin response (GSR). METHODS: We collected data from 122 participants across 3 European cities as part of the Physical Activity through Sustainable Transport Approaches (PASTA) study, including: GSR measured every minute alongside confounders (physical activity, near-body temperature) during three separate weeks covering 3 seasons; sociodemographic and travel information through questionnaires. Causal relationships between travel in different modes (the "treatment") and stress were established by using a propensity score matching (PSM) approach to adjust for potential confounding and estimating linear mixed models (LMM) with individuals as random effects to account for repeated measurements. In three separate analyses, we compared GSR while cycling to not cycling, then walking to not walking then motorized (public or private) travel to any activity other than motorized travel. RESULTS: Depending on LMM formulations used, cycling reduces 1-minute GSR by 5.7% [95% CI: 2.0-16.9%] to 11.1% [95% CI: 5.0-24.4%] compared to any other activity. Repeating the analysis for other modes we find that: walking is also beneficial, reducing GSR by 3.9% [95% CI: 1.4-10.7%] to 5.7% [95% CI: 2.6-12.3%] compared to any other activity; motorized mode (private or public) in reverse increases GSR by up to 1.1% [95% CI: 0.5-2.9%]. DISCUSSION: Active travel offers a welcome way to reduce stress in urban dwellers' daily lives. Stress can be added to the growing number of evidence-based reasons for promoting active travel in cities.

Denser Retinal Microvascular Network Is Inversely Associated With Behavioral Outcomes and Sustained Attention in Children.

Changes in geometry of the retinal microvascular network, including vessel width, vessel density, and tortuosity, have been associated with neurological disorders in adults. We investigated metrics of the retinal microvasculature in association with behavior and cognition in 8- to 12-year-old children. Digital fundus images of 190 children (48.2% girls, mean age 9.9 years) were used to calculate retinal vessel diameters, fractal dimension, lacunarity, and tortuosity. Parents filled out a Strengths and Difficulties Questionnaire (SDQ) for behavioral screening. Cognitive performance testing included a computerized version of the Stroop test (selective attention), the Continuous Performance (sustained attention), the Digit-Symbol (visual scanning and information-processing speed) and the Pattern Comparison (visuospatial analytic ability) tests from the Neurobehavioral Evaluation System (NES3) battery. Retinal vessel geometry was significantly associated with the SDQ problem score, which increased with 1.1 points (95% CI: 0.3 to 1.9 points) per interquartile (IQR) increment in retinal fractal dimension, and decreased 1.4 points (95% CI: -2.4 to -0.4 points) or decreased 1.0 points (95% CI: -2.1 to 0.1 points) per IQR increment in retinal vascular lacunarity or tortuosity, respectively. Sensitivity analyses showed that results were driven by the hyperactivity/inattention and conduct problem scales of the SDQ. Correspondingly, mean reaction time on the Continuous Performance test increased by 11 ms (95% CI: 4.4 to 17.6 ms) with an IQR increase in fractal dimension. The results indicate that a denser retinal microvascular network, exemplified by a higher fractal dimension and lower lacunarity, are inversely associated with behavioral outcomes and sustained attention in children.

Retinal microvascular complexity comparing mono- and multifractal dimensions in relation to cardiometabolic risk factors in a Middle Eastern population.

PURPOSE: Metrics that capture changes in the retinal microvascular structure are relevant in the context of cardiometabolic disease development. The microvascular topology is typically quantified using monofractals, although it obeys more complex multifractal rules. We study mono- and multifractals of the retinal microvasculature in relation to cardiometabolic factors. METHODS: The cross-sectional retrospective study used data from 3000 Middle Eastern participants in the Qatar Biobank. A total of 2333 fundus images (78%) passed quality control and were used for further analysis. The monofractal (Df ) and five multifractal metrics were associated with cardiometabolic factors using multiple linear regression and were studied in clinically relevant subgroups. RESULTS: Df and multifractals are lowered in function of age, and Df is lower in males compared to females. In models corrected for age and sex, Df is significantly associated with BMI, insulin, systolic blood pressure, glycated haemoglobin (HbA1c), albumin, LDL and total cholesterol concentrations. Multifractals are negatively associated with systolic and diastolic blood pressure, glucose and the WHO/ISH cardiovascular risk score. Df was higher, and multifractal curve asymmetry was lower in diabetic patients (HbA1c > 6.5%) compared to healthy individuals (HbA1c < 5.7%). Insulin resistance (insulin ≥ 23 mcU/mL) was associated with significantly lower Df values. CONCLUSION: One or more fractal metrics are in association with sex, age, BMI, systolic and diastolic blood pressure and biochemical blood measurements in a Middle Eastern population study. Follow-up studies aiming at investigating retinal microvascular changes in relation to cardiometabolic risk should analyse both monofractal and multifractal metrics for a more comprehensive microvascular picture.

Combination of snapshot hyperspectral retinal imaging and optical coherence tomography to identify Alzheimer's disease patients.

INTRODUCTION: The eye offers potential for the diagnosis of Alzheimer's disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. METHODS: In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460-620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. RESULTS: Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60-0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. CONCLUSIONS: This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

Evaluation of Different Recruitment Methods: Longitudinal, Web-Based, Pan-European Physical Activity Through Sustainable Transport Approaches (PASTA) Project.

BACKGROUND: Sufficient sample size and minimal sample bias are core requirements for empirical data analyses. Combining opportunistic recruitment with a Web-based survey and data-collection platform yields new benefits over traditional recruitment approaches. OBJECTIVE: This paper aims to report the success of different recruitment methods and obtain data on participants' characteristics, participation behavior, recruitment rates, and representativeness of the sample. METHODS: A longitudinal, Web-based survey was implemented as part of the European PASTA (Physical Activity through Sustainable Transport Approaches) project, between November 2014 and December 2016. During this period, participants were recruited from 7 European cities on a rolling basis. A standardized guide on recruitment strategy was developed for all cities, to reach a sufficient number of adult participants. To make use of the strengths and minimize weakness, a combination of different opportunistic recruitment methods was applied. In addition, the random sampling approach was applied in the city of Örebro. To reduce the attrition rate and improve real-time monitoring, the Web-based platform featured a participant's and a researchers' user interface and dashboard. RESULTS: Overall, 10,691 participants were recruited; most people found out about the survey through their workplace or employer (2300/10691, 21.51%), outreach promotion (2219/10691, 20.76%), and social media (1859/10691, 17.39%). The average number of questionnaires filled in per participant varied significantly between the cities (P<.001), with the highest number in Zurich (11.0, SE 0.33) and the lowest in Örebro (4.8, SE 0.17). Collaboration with local organizations, the use of Facebook and mailing lists, and direct street recruitment were the most effective approaches in reaching a high share of participants (P<.001). Considering the invested working hours, Facebook was one of the most time-efficient methods. Compared with the cities' census data, the composition of study participants was broadly representative in terms of gender distribution; however, the study included younger and better-educated participants. CONCLUSIONS: We observed that offering a mixed recruitment approach was highly effective in achieving a high participation rate. The highest attrition rate and the lowest average number of questionnaires filled in per participant were observed in Örebro, which also recruited participants through random sampling. These findings suggest that people who are more interested in the topic are more willing to participate and stay in a survey than those who are selected randomly and may not have a strong connection to the research topic. Although direct face-to-face contacts were very effective with respect to the number of recruited participants, recruiting people through social media was not only effective but also very time efficient. The collected data are based on one of the largest recruited longitudinal samples with a common recruitment strategy in different European cities.

Effects of physical activity and air pollution on blood pressure.

AIM: To assess the main and interaction effects of black carbon and physical activity on arterial blood pressure in a healthy adult population from three European cities using objective personal measurements over short-term (hours and days) and long-term exposure. METHODS: A panel study of 122 healthy adults was performed in three European cities (Antwerp, Barcelona, and London). In 3 seasons between March 2015 and March 2016, each participant wore sensors for one week to objectively measure their exposure to black carbon and monitor their physical activity continuously. Blood pressure was assessed three times during the week: at the beginning (day 0), in the middle (day 4), and at the end (day 7). Associations of black carbon and physical activity with blood pressure and their interactions were investigated with linear regression models and multiplicative interaction terms, adjusting for all the potential confounders. RESULTS: In multiple exposure models, we did not see any effects of black carbon on blood pressure but did see effects on systolic blood pressure of moderate-to-vigorous physical activity effect that were statistically significant from 1 h to 8 h after exposure and for long-term exposure. For a 1METhour increase of moderate-to-vigorous physical activity, the difference in the expected mean systolic blood pressure varied from -1.46 mmHg (95%CI -2.11, -0.80) for 1 h mean exposure, to -0.29 mmHg (95%CI -0.55, -0.03) for 8 h mean exposure, and -0.05 mmHg (95%CI -0.09, -0.00) for long-term exposure. There were little to no interaction effects. CONCLUSIONS: Results from this study provide evidence that short-term and long-term exposure to moderate-to-vigorous physical activity is associated with a decrease in systolic blood pressure levels. We did not find evidence for a consistent main effect of black carbon on blood pressure, nor any interaction between black carbon and physical activity levels.

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.

Short-term effects of physical activity, air pollution and their interaction on the cardiovascular and respiratory system.

Physical activity (PA) in urban environments may lead to increased inhalation of air pollutants. As PA and air pollution (AP) have respectively beneficial and detrimental effects on the cardiorespiratory system, the responses to these exposures can interact. Therefore, we assessed the short-term effects of PA, AP and their interaction on a set of subclinical cardiovascular and respiratory outcomes in a panel of healthy adults: heart rate variability (HRV), retinal vessel diameters, lung function and fractional exhaled nitric oxide (FeNO). One hundred twenty two participants measured their PA level and exposure to black carbon (BC), a marker of AP exposure, with wearable sensors during an unscripted week in three different seasons. The study was part of the PASTA project in three European cities (Antwerp: 41 participants, Barcelona: 41 participants, London: 40 participants). At the end of each measurement week, the health outcomes were evaluated. Responses to PA, BC and their interaction were assessed with mixed effect regression models. Separate models were used to account for a 2-h and 24-h time window. During the 2-h time window, HRV and lung function changed statistically significantly in response to PA (METhours) and logarithmic BC (%change). Changes in HRV marked an increased sympathetic tone with both PA (logarithmic LF/HF: +7%; p < 0.01) and BC (logarithmic HF: -19%; p < 0.05). In addition, PA provoked bronchodilation which was illustrated by a significant increase in lung function (FEV1: +15.63 mL; p < 0.05). While a BC %increase was associated with a significant lung function decrease (PEF: -0.10 mL; p < 0.05), the interaction indicated a potential protective effect of PA (p < 0.05). We did not observe a response of the retinal vessel diameters. Most subclinical outcomes did not change in the 24-h time window (except for a few minor changes in LF/HF, FeNO and PEF). Our results on the separate and combined effects of short-term PA and AP exposure on subclinical markers of the cardiorespiratory system are relevant for public health. We provide insights on the physiological responses of multiple, complementary markers. This may move further research towards elucidating potential pathways to disease and the long-term clinical impact of the observed physiological changes.

Black Carbon Reduces the Beneficial Effect of Physical Activity on Lung Function.

INTRODUCTION: When physical activity is promoted in urban outdoor settings (e.g., walking and cycling), individuals are also exposed to air pollution. It has been reported that short-term lung function increases as a response to physical activity, but this beneficial effect is hampered when elevated air pollution concentrations are observed. Our study assessed the long-term impact of air pollution on the pulmonary health benefit of physical activity. METHODS: Wearable sensors were used to monitor physical activity levels (SenseWear) and exposure to black carbon (microAeth) of 115 healthy adults during 1 wk in three European cities (Antwerp, Barcelona, London). The experiment was repeated in three different seasons to approximate long-term behavior. Spirometry tests were performed at the beginning and end of each measurement week. All results were averaged on a participant level as a proxy for long-term lung function. Mixed effect regression models were used to analyze the long-term impact of physical activity, black carbon and their interaction on lung function parameters, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow (FEF)25-75, and peak expiratory flow. Interaction plots were used to interpret the significant interaction effects. RESULTS: Negative interaction effects of physical activity and black carbon exposure on FEV1 (P = 0.07), FEV1/FVC (P = 0.03), and FEF25-75 (P = 0.03) were observed. For black carbon concentrations up to approximately 1 µg·m, an additional MET·h·wk resulted in a trend toward lung function increases (FEV1, FEV1/FVC, and FEF25-75 increased 5.6 mL, 0.1% and 14.5 mL·s, respectively). CONCLUSIONS: We found that lung function improved with physical activity at low black carbon levels. This beneficial effect decreased in higher air pollution concentrations. Our results suggest a greater need to reduce air pollution exposures during physical activity.

Short-term air pollution exposure decreases lung function: a repeated measures study in healthy adults.

BACKGROUND: Daily changes in ambient concentrations of particulate matter, nitrogen oxides and ozone are associated with increased cardiopulmonary morbidity and mortality, with the lungs and their function being a vulnerable target. METHODS: To evaluate the association between daily changes in air pollution and lung function in healthy adults we obtained annual lung function measurements from a routine worker health surveillance program not designed for research purposes. Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), FEV1/FVC and Peak Expiratory flow (PEF) from a cohort of 2449 employees were associated with daily measurements of PM10, NO2 and ozone at a nearby monitoring station in the North of Belgium. Repeated measures were available for the period 2011-2015. RESULTS: The mean (SD) PM10 concentration on the day of the lung function test was 24.9 (15.5) µg/m3. A 10 µg PM10/m3 increase on the day of the clinical examination was associated with a 18.9 ml lower FVC (95% CI: -27.5 to -10.3, p < 0.0001), 12.8 ml lower FEV1 (-19.1 to -6.5; p < 0.0001), and a 51.4 ml/s lower PEF (-75.0 to -27.0; p < 0.0001). The FEV1/FVC-ratio showed no associations. An increase of 10 µgNO2/m3 was associated with a reduction in PEF (-66.1 ml/s (-106.6 to -25.6; p < 0.001)) on the day of the examination. CONCLUSIONS: We found negative associations between daily variations in ambient air pollution and FVC, FEV1 and PEF in healthy adults.

Physical activity and sedentary behaviour in daily life: A comparative analysis of the Global Physical Activity Questionnaire (GPAQ) and the SenseWear armband.

Reduction of sedentary time and an increase in physical activity offer potential to improve public health. However, quantifying physical activity behaviour under real world conditions is a major challenge and no standard of good practice is available. Our aim was to compare the results of physical activity and sedentary behaviour obtained with a self-reported instrument (Global Physical Activity Questionnaire (GPAQ)) and a wearable sensor (SenseWear) in a repeated measures study design. Healthy adults (41 in Antwerp, 41 in Barcelona and 40 in London) wore the SenseWear armband for seven consecutive days and completed the GPAQ on the final day. This was repeated three times. We used the Wilcoxon signed rank sum test, Spearman correlation coefficients, mixed effects regression models and Bland-Altman plots to study agreement between both methods. Mixed models were used to assess the effect of personal characteristics on the absolute and relative difference between estimates obtained with the GPAQ and SenseWear. Moderate to vigorous energy expenditure and duration derived from the GPAQ were significantly lower (p<0.05) compared to the SenseWear, yet these variables showed significant correlations ranging from 0.45 to 0.64. Estimates of vigorous-intensity physical activity in particular showed high similarity (r>0.59). Results for sedentary behaviour did not differ, yet were poorly correlated (r<0.25). The differences between all variables were reproducible across repeated measurements. In addition, we observed a relationship between these differences and BMI, body fat and physical activity domain. Due to the lack of a standardized protocol, results from different studies measuring physical activity and sedentary behaviour are difficult to compare. Therefore, we suggested an easy-to-implement approach for future studies adding the GPAQ to the wearable of choice as a basis for comparisons.

Wearable Sensors for Personal Monitoring and Estimation of Inhaled Traffic-Related Air Pollution: Evaluation of Methods.

Physical activity and ventilation rates have an effect on an individual's dose and may be important to consider in exposure-response relationships; however, these factors are often ignored in environmental epidemiology studies. The aim of this study was to evaluate methods of estimating the inhaled dose of air pollution and understand variability in the absence of a true gold standard metric. Five types of methods were identified: (1) methods using (physical) activity types, (2) methods based on energy expenditure, METs (metabolic equivalents of task), and oxygen consumption, (3) methods based on heart rate or (4) breathing rate, and (5) methods that combine heart and breathing rate. Methods were compared using a real-life data set of 122 adults who wore devices to track movement, black carbon air pollution, and physiological health markers for 3 weeks in three European cities. Different methods for estimating minute ventilation performed well in relative terms with high correlations among different methods, but in absolute terms, ignoring increased ventilation during day-to-day activities could lead to an underestimation of the daily dose by a factor of 0.08-1.78. There is no single best method, and a multitude of methods are currently being used to approximate the dose. The choice of a suitable method for determining the dose in future studies will depend on both the size and the objectives of the study.

Multimedia & PBPK modelling with MERLIN-Expo versus biomonitoring for assessing Pb exposure of pre-school children in a residential setting.

This paper reports on a case study - conducted within the European FP7 project "4FUN" - focusing on exposure of pre-school children to lead resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed and simulated with the MERLIN-Expo tool to estimate external Pb exposure as well as the Pb body burden in children living in the vicinity of the former industrial sites as compared to children living in adjacent areas and a reference area. Simulations were run for several scenarios ranging from very simple to rather complex in order to study the effect of different simulation approaches (e.g., deterministic vs. probabilistic, individual vs. aggregated population exposure) and different exposure scenarios (e.g., with vs. without considering local food consumption or time activity patterns) on the model outcomes (predicted concentrations of Pb in environmental and human matrices). This paper discusses the two most complex scenarios, namely exposure at the aggregated population level and at the individual level for a random sub-sample of subjects, respectively. In the final and most realistic exposure scenario, simulating individual lead exposure, model predictions were shown to be higher than the biomonitoring data. Blood Pb levels in children, irrespective of the area they lived in, were overpredicted by MERLIN-Expo with a factor of about 2 on average. The model predictions for individual children overlap with the prediction interval calculated by MERLIN-Expo based on population averages, demonstrating the use of probabilistic approaches in risk assessment. While these results constitute a first verification of the model performance of MERLIN-Expo dealing with inorganic pollutants in a complex real-world exposure scenario and a demonstration of the robustness of the modelling tool, further validation and benchmarking efforts are required for a larger number of inorganic pollutants and different exposure settings.

Assessing multimedia/multipathway exposures to inorganic arsenic at population and individual level using MERLIN-Expo.

In this study, we report on model simulations performed using the newly developed exposure tool, MERLIN-Expo, in order to assess inorganic arsenic (iAs) exposure to adults resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed to estimate external iAs exposure as well as the toxicologically relevant As (tAs, i.e., iAs, MMA and DMA) body burden in adults living in the vicinity of the former industrial sites as compared to adults living in adjacent areas and a reference area. Two scenarios are discussed: a first scenario studying exposure to iAs at the aggregated population level and a second scenario studying exposure at the individual level for a random sub-sample of subjects in each of the three different study areas. These two scenarios only differ in the type of human related input data (i.e., time-activity data, ingestion rates and consumption patterns) that were used, namely averages (incl. probability density functions, PDFs) in the simulation at population level and subject-specific values in the simulation at individual level. The model predictions are shown to be lower than the corresponding biomonitoring data from the monitoring campaign. Urinary tAs levels in adults, irrespective of the area they lived in, were under-predicted by MERLIN-Expo by 40% on average. The model predictions for individual adults, by contrast, under-predict the biomonitoring data by 7% on average, but with more important under-predictions for subjects at the upper end of exposure. Still, average predicted urinary tAs levels from the simulations at population level and at individual level overlap, and, at least for the current case, lead to similar conclusions. These results constitute a first and partial verification of the model performance of MERLIN-Expo when dealing with iAs in a complex site-specific exposure scenario, and demonstrate the robustness of the modelling tool for these situations.

Physical Activity through Sustainable Transport Approaches (PASTA): a study protocol for a multicentre project.

INTRODUCTION: Only one-third of the European population meets the minimum recommended levels of physical activity (PA). Physical inactivity is a major risk factor for non-communicable diseases. Walking and cycling for transport (active mobility, AM) are well suited to provide regular PA. The European research project Physical Activity through Sustainable Transport Approaches (PASTA) pursues the following aims: (1) to investigate correlates and interrelations of AM, PA, air pollution and crash risk; (2) to evaluate the effectiveness of selected interventions to promote AM; (3) to improve health impact assessment (HIA) of AM; (4) to foster the exchange between the disciplines of public health and transport planning, and between research and practice. METHODS AND ANALYSIS: PASTA pursues a mixed-method and multilevel approach that is consistently applied in seven case study cities. Determinants of AM and the evaluation of measures to increase AM are investigated through a large scale longitudinal survey, with overall 14,000 respondents participating in Antwerp, Barcelona, London, Örebro, Rome, Vienna and Zurich. Contextual factors are systematically gathered in each city. PASTA generates empirical findings to improve HIA for AM, for example, with estimates of crash risks, factors on AM-PA substitution and carbon emissions savings from mode shifts. Findings from PASTA will inform WHO's online Health Economic Assessment Tool on the health benefits from cycling and/or walking. The study's wide scope, the combination of qualitative and quantitative methods and health and transport methods, the innovative survey design, the general and city-specific analyses, and the transdisciplinary composition of the consortium and the wider network of partners promise highly relevant insights for research and practice. ETHICS AND DISSEMINATION: Ethics approval has been obtained by the local ethics committees in the countries where the work is being conducted, and sent to the European Commission before the start of the survey. The PASTA website (http://www.pastaproject.eu) is at the core of all communication and dissemination activities.

Physical Activity through Sustainable Transport Approaches (PASTA): protocol for a multi-centre, longitudinal study.

BACKGROUND: Physical inactivity is one of the leading risk factors for non-communicable diseases, yet many are not sufficiently active. The Physical Activity through Sustainable Transport Approaches (PASTA) study aims to better understand active mobility (walking and cycling for transport solely or in combination with public transport) as an innovative approach to integrate physical activity into individuals' everyday lives. The PASTA study will collect data of multiple cities in a longitudinal cohort design to study correlates of active mobility, its effect on overall physical activity, crash risk and exposure to traffic-related air pollution. METHODS/DESIGN: A set of online questionnaires incorporating gold standard approaches from the physical activity and transport fields have been developed, piloted and are now being deployed in a longitudinal study in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich). In total, 14000 adults are being recruited (2000 in each city). A first questionnaire collects baseline information; follow-up questionnaires sent every 13 days collect prospective data on travel behaviour, levels of physical activity and traffic safety incidents. Self-reported data will be validated with objective data in subsamples using conventional and novel methods. Accelerometers, GPS and tracking apps record routes and activity. Air pollution and physical activity are measured to study their combined effects on health biomarkers. Exposure-adjusted crash risks will be calculated for active modes, and crash location audits are performed to study the role of the built environment. Ethics committees in all seven cities have given independent approval for the study. DISCUSSION: The PASTA study collects a wealth of subjective and objective data on active mobility and physical activity. This will allow the investigation of numerous correlates of active mobility and physical activity using a data set that advances previous efforts in its richness, geographical coverage and comprehensiveness. Results will inform new health impact assessment models and support efforts to promote and facilitate active mobility in cities.