Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California.

Rationale: Particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 µm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (ptrend = .003) and cumulative exposure (ptrend = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Long-term exposure to air pollution and incidence of gastric and the upper aerodigestive tract cancers in a pooled European cohort: The ELAPSE project.

Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone in the warm season (O3w) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 5,305,133 and 5,434,843 person-years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM2.5, NO2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00-1.33) per 5 µg/m3 increase in PM2.5, 1.19 (1.08-1.30) per 10 µg/m3 increase in NO2, 1.14 (1.04-1.26) per 0.5 × 10-5 m-1 increase in BC and 0.81 (0.72-0.92) per 10 µg/m3 increase in O3w. We found no association between long-term ambient air pollution exposure and incidence of gastric cancer, while for long-term exposure to PM2.5, NO2 and BC increased incidence of UADT cancer was observed.

Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients.

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

Associations of Anti-COVID-19 Measures and Lifestyle Changes During the COVID-19 Pandemic With Sleep Patterns in the Netherlands: A Longitudinal Study.

Although there is scientific evidence for an increased prevalence of sleep disorders during the coronavirus disease 2019 (COVID-19) pandemic, there is still limited information on how lifestyle factors might have affected sleep patterns. Therefore, we followed a large cohort of participants in the Netherlands (n = 5,420) for up to 1 year (September 2020-2021) via monthly Web-based questionnaires to identify lifestyle changes (physical activity, cigarette smoking, alcohol consumption, electronic device use, and social media use) driven by anti-COVID-19 measures and their potential associations with self-reported sleep (latency, duration, and quality). We used the Containment and Health Index (CHI) to assess the stringency of anti-COVID-19 measures and analyzed associations through multilevel ordinal response models. We found that more stringent anti-COVID-19 measures were associated with higher use of electronic devices (per interquartile-range increase in CHI, odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.40, 1.53), less physical activity (OR = 0.94, 95% CI: 0.90, 0.98), lower frequency of alcohol consumption (OR = 0.63, 95% CI: 0.60, 0.66), and longer sleep duration (OR = 1.11, 95% CI: 1.05, 1.16). Lower alcohol consumption frequency and higher use of electronic devices and social media were associated with longer sleep latency. Lower physical activity levels and higher social media and electronic device use were related to poorer sleep quality and shorter sleep duration.

Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of 4 regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case analysis, and multiple imputation in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the United Kingdom. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with complete-case analysis or multiple imputation. We showed that RC methods resulted in more accurate estimation of the relationship between mobile phone use and health outcomes by combining self-reported data with objective operator-recorded data available for a subset of participants.

Clinical implications of airway obstruction with normal or low FEV1 in childhood and adolescence.

BACKGROUND: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV1 (classic) or a normal FEV1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear. AIMS: To investigate the association between airway obstruction with a low or normal FEV1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR). METHODS: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV1:FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV1

Time-varying exposure to food retailers and cardiovascular disease hospitalization and mortality in the netherlands: a nationwide prospective cohort study.

BACKGROUND: Very few studies to date investigated the prospective association of changes in exposure to the food environment with cardiovascular disease (CVD) risk. We aim to explore if time-varying exposure to the food environment was associated with hospitalization and mortality due to total and specific types of CVD in The Netherlands. METHODS: In this prospective cohort study, 4,641,435 Dutch adults aged 35 + years who did not change residence in 2002-2018 were identified through registry data. Exposure to the food environment was defined as time-varying Food Environment Healthiness Index (FEHI) scores (range: - 5 to 5) and time-varying kernel density of specific food retailers (e.g., fast food outlets, supermarkets) around the home location between 2004 and 2018. The main outcome measures were hospitalization and mortality due to overall CVD, stroke, HF, and CHD occurring between 2004 and 2020, based on hospital and death registries. RESULTS: In Cox regression models, each unit increase in the FEHI was associated with a lower hospitalization and mortality of CVD (hospitalization hazard ratio (HRh) = 0.90 (0.89 to 0.91), mortality hazard ratio (HRm) = 0.85 (0.82 to 0.89)), CHD (HRh = 0.88 (0.85 to 0.91), HRm = 0.80 (0.75 to 0.86)), stroke (HRh = 0.89 (0.84 to 0.93)), HRm = 0.89 (0.82 to 0.98)), and HF (HRh = 0.90 (0.84-0.96), HRm = 0.84 (0.76 to 0.92)). Increased density of local food shops, fast food outlets, supermarkets, and convenience stores and decreased density of food delivery outlets and restaurants were associated with a higher risk of CVD, CHD, stroke, and HF hospitalization and mortality. CONCLUSIONS: In this observational longitudinal study, changes in exposure to a healthier food environment over 14 years were associated with a risk reduction in CVD hospitalization and mortality, in particular in urbanized areas and for younger adults and those with higher incomes.

Socioeconomic status, smoking, and lung cancer: mediation and bias analysis in the SYNERGY study.

BACKGROUND: Increased lung-cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits, and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects (NDE) and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately as well as by multiple quantitative bias analysis, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung-cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung-cancer risk in the multiple bias analysis. Lung-cancer risks remained increased for lower SES groups, with higher risks in men [4th versus 1st (highest) SES quartile: CDE 1.50 (SI 1.32-1.69)] than women [CDE 1.20 (SI 1.01-1.45)]. NDE were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung-cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis.

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Associations of light exposure patterns with sleep among Dutch children: The ABCD cohort study.

Light exposure affects the circadian system and consequently can affect sleep quality. Only few studies examined this relationship in children. We evaluated associations between light exposure patterns and sleep metrics in children. We measured the sleep parameters of 247 Dutch children, aged between 11 and 13 years and recruited from the ABCD cohort, using actigraphy and sleep records for 7 consecutive nights. Personal light exposures were measured with a light meter during the whole day and night. We applied generalized mixed-effects regression models, adjusted for possible confounders, to evaluate the associations of light exposure patterns on sleep duration, sleep efficiency and sleep-onset delay. In the models mutually adjusted for potential confounders, we found the amount of hours between the first time of bright light in the morning and going to sleep and the duration of bright light to be significantly associated with decreased sleep duration (in min; ß: -2.02 [95% confidence interval: -3.84, -0.25], ß: -8.39 [95% confidence interval: -16.70, -0.07], respectively) and with shorter sleep-onset delay (odds ratio: 0.88 [95% confidence interval: 0.80, 0.97], odds ratio: 0.40 [95% confidence interval: 0.19, 0.87], respectively). Increased light intensities at night were associated with decreased sleep duration (T2 ß: -8.54 [95% confidence interval: -16.88, -0.20], T3 ß: -14.83 [95% confidence interval: -28.04, -1.62]), while increased light intensities before going to bed were associated with prolonged sleep onset (odds ratio: 4.02 [95% confidence interval: 2.09, 7.73]). These findings further suggest that children may be able to influence their sleep quality by influencing the light exposure patterns during day and night.

Chronotype in relation to shift work: A cohort study among 37,731 female nurses.

Chronotype may affect tolerance for circadian disruption induced by shift work. This study examines the association between chronotype, self-reported sleep timing, shift type preference, and sleep problems among nurses, and studies chronotype stability over time. The study included 37,731 Dutch female nurses who completed a baseline (2011) and follow-up questionnaire (2017), with information on shift work (e.g., job history, shift type preference [collected in 2017 only]), and sleep characteristics (e.g., chronotype, preferred sleep-wake time in a work-free period [collected in 2017 only], and sleep problems between working days according to Medical Outcomes Study-Sleep Problem Index II [MOS-SPI-II]). The association between chronotype and sleep timing was examined using (age-adjusted) linear regression. Associations between chronotype and shift type preference and sleep problems (MOS-SPI-II >30) were examined using ordered logistic and Poisson regression, respectively. With later chronotype, midsleep time increased (definite evening vs. intermediate types [reference]: ß = 55 min, 95% confidence interval [95% CI]: 54-55), the odds ratio (OR) for 1-point increase in preference for night (2.68; 95% CI: 2.48-2.90) and evening shifts increased (OR 2.20; 95% CI: 2.03-2.38), while the odds for day (OR 0.17; 95% CI: 0.16-0.18) and morning shifts (OR 0.22; 95% CI: 0.21-0.24) decreased. Intermediate chronotype was associated with fewer sleep problems (median MOS-SPI-II = 27.2, p < 0.01), compared with definite morning (28.9) and evening types (31.7). This study shows that chronotype is associated with sleep-wake times in a work-free period, shift type preference, and sleep problems in nurses. Future studies on the association of shift work-induced circadian disruption and health outcomes should therefore consider chronotype as effect-modifier.

Hyperlocal Air Pollution Mapping: A Scalable Transfer Learning LUR Approach for Mobile Monitoring.

Addressing the challenge of mapping hyperlocal air pollution in areas without local monitoring, we evaluated unsupervised transfer learning-based land-use regression (LUR) models developed using mobile monitoring data from other cities: CORrelation ALignment (Coral) and its inverse distance-weighted modification (IDW_Coral). These models mitigated domain shifts and transferred patterns learned from mobile air quality monitoring campaigns in Copenhagen and Rotterdam to estimate annual average air pollution levels in Amsterdam (50m road segments) without involving any Amsterdam measurements in model development. For nitrogen dioxide (NO2), IDW_Coral outperformed Copenhagen and Rotterdam LUR models directly applied to Amsterdam, achieving MAE (4.47 µg/m3) and RMSE (5.36 µg/m3) comparable to a locally fitted LUR model (AMS_SLR) developed using Amsterdam mobile measurements collected for 160 days. IDW_Coral yielded an R2 of 0.35, similar to that of the AMS_SLR based on 20 collection days, suggesting a minimum requirement of 20-day mobile monitoring to capture city-specific insights. For ultrafine particles (UFP), IDW_Coral's citywide predictions strongly correlated with previously published mixed-effect models fitted with 160-day Amsterdam measurements (Pearson correlation of 0.71 for UFP and 0.72 for NO2). IDW_Coral demands no direct measurements in the target area, showcasing its potential for large-scale applications and offering significant economic efficiencies in executing mobile monitoring campaigns.

Validity of Mobility-Based Exposure Assessment of Air Pollution: A Comparative Analysis with Home-Based Exposure Assessment.

Air pollution exposure is typically assessed at the front door where people live in large-scale epidemiological studies, overlooking individuals' daily mobility out-of-home. However, there is limited evidence that incorporating mobility data into personal air pollution assessment improves exposure assessment compared to home-based assessments. This study aimed to compare the agreement between mobility-based and home-based assessments with personal exposure measurements. We measured repeatedly particulate matter (PM2.5) and black carbon (BC) using a sample of 41 older adults in the Netherlands. In total, 104 valid 24 h average personal measurements were collected. Home-based exposures were estimated by combining participants' home locations and temporal-adjusted air pollution maps. Mobility-based estimates of air pollution were computed based on smartphone-based tracking data, temporal-adjusted air pollution maps, indoor-outdoor penetration, and travel mode adjustment. Intraclass correlation coefficients (ICC) revealed that mobility-based estimates significantly improved agreement with personal measurements compared to home-based assessments. For PM2.5, agreement increased by 64% (ICC: 0.39-0.64), and for BC, it increased by 21% (ICC: 0.43-0.52). Our findings suggest that adjusting for indoor-outdoor pollutant ratios in mobility-based assessments can provide more valid estimates of air pollution than the commonly used home-based assessments, with no added value observed from travel mode adjustments.

Dioxin(-like)-Related Biological Effects through Integrated Chemical-wide and Metabolome-wide Analyses.

Dioxin(-like) exposures are linked to adverse health effects, including cancer. However, metabolic alterations induced by these chemicals remain largely unknown. Beyond known dioxin(-like) compounds, we leveraged a chemical-wide approach to assess chlorinated co-exposures and parent compound products [termed dioxin(-like)-related compounds] among 137 occupational workers. Endogenous metabolites were profiled by untargeted metabolomics, namely, reversed-phase chromatography with negative electrospray ionization (C18-negative) and hydrophilic interaction liquid chromatography with positive electrospray ionization (HILIC-positive). We performed a metabolome-wide association study to select dioxin(-like) associated metabolic features using a 20% false discovery rate threshold. Metabolic features were then characterized by pathway enrichment analyses. There are no significant features associated with polychlorinated dibenzo-p-dioxins (PCDDs), a subgroup of known dioxin(-like) compounds. However, 3,110 C18-negative and 2,894 HILIC-positive features were associated with at least one of the PCDD-related compounds. Abundant metabolic changes were also observed for polychlorinated dibenzofuran-related and polychlorinated biphenyl-related compounds. These metabolic features were primarily enriched in pathways of amino acids, lipid and fatty acids, carbohydrates, cofactors, and nucleotides. Our study highlights the potential of chemical-wide analysis for comprehensive exposure assessment beyond targeted chemicals. Coupled with advanced endogenous metabolomics, this approach allows for an in-depth exploration of metabolic alterations induced by environmental chemicals.