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Summary: Background: Transportation noise has been linked with cardiometabolic outcomes, yet whether it is a risk factor for atrial fibrillation (AF) remains inconclusive. We aimed to assess whether transportation noise was associated with AF in a large, pooled Nordic cohort. Methods: We pooled data from 11 Nordic cohorts, totaling 161,115 participants. Based on address history from five years before baseline until end of follow-up, road, railway, and aircraft noise was estimated at a residential level. Incident AF was ascertained via linkage to nationwide patient registries. Cox proportional hazards models were utilized to estimate associations between running 5-year time-weighted mean transportation noise (Lden) and AF after adjusting for sociodemographics, lifestyle, and air pollution. Findings: We identified 18,939 incident AF cases over a median follow-up of 19.6 years. Road traffic noise was associated with AF, with a hazard ratio (HR) and 95% confidence interval (CI) of 1.02 (1.00–1.04) per 10-dB of 5-year mean time-weighted exposure, which changed to 1.03 (1.01–1.06) when implementing a 53-dB cut-off. In effect modification analyses, the association for road traffic noise and AF appeared strongest in women and overweight and obese participants. Compared to exposures ≤40 dB, aircraft noise of 40.1–50 and > 50 dB were associated with HRs of 1.04 (0.93–1.16) and 1.12 (0.98–1.27), respectively. Railway noise was not associated with AF. We found a HR of 1.19 (1.02–1.40) among people exposed to noise from road (≥45 dB), railway (>40 dB), and aircraft (>40 dB) combined. Interpretation: Road traffic noise, and possibly aircraft noise, may be associated with elevated risk of AF. Funding: NordForsk.

Abstract Increasing recognition of germline DDX41 variants in patients with hematological malignancies prompted us to provide DDX41‐specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the DDX41 predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%–5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline DDX41 variant, while half of them acquire a somatic second hit in the other allele. DDX41‐associated MNs exhibit unique clinical characteristics compared to other hematological malignancies with germline predisposition: MNs occur mostly at advanced age and follow an indolent clinical course. Male carriers are more prone to develop MDS or AML than females. DDX41‐associated MN is often hypoplastic, and the malignancy may be preceded by cytopenias.

BACKGROUND: Urban-rural differences in schizophrenia risk have been widely evidenced across Western countries. However, explanation of these differences is lacking. We aimed to identify contextual risk factors for schizophrenia that explain urban-rural differences in schizophrenia risk. METHODS: Utilizing Danish population-based registers, we partitioned Denmark into 1885 geographic neighborhoods homogeneously sized in terms of population. Information on the entire Danish population from 1981 to 2016 was used to quantify a spectrum of neighborhood-level domains. We subsequently conducted multilevel survival analyses following persons born in Denmark from 1971 to 1982 for the development of schizophrenia allowing for clustering of people within neighborhoods. We used this method to tease apart the effects of individual, specific, and general contextual risk factors for schizophrenia. RESULTS: A significant general contextual effect in schizophrenia risk across neighborhoods was estimated (Medium Incidence Rate Ratio (MRR):1.41; 95% CI:1.35-1.48). Most of the specific contextual factors examined were associated with schizophrenia risk. For instance, neighborhood-level proportion of lone adult households (Incidence Rate Ratios (IRR):1.53; 95% CI:1.44-1.63) had largest risk estimate. Adjustment for all individual-level and specific contextual constructs reduced the IRR for urbanicity from 1.98 (95% CI:1.77-2.22) to 1.30 (95% CI:1.11-1.51). CONCLUSIONS: In the largest prospective multilevel survival analyses of schizophrenia risk conducted to date, multiple neighborhood-level characteristics were associated with raised schizophrenia risk, with these contextual factors explaining most of the elevated risk linked with urbanicity. However, the unexplained heterogeneity that was evident in our multilevel models indicates that our understanding of the role of urbanicity in schizophrenias etiology remains incomplete.

Abstract Background Anticoagulants (AC) were introduced in March 2020 as standard of care in nursing home (NH) residents affected with COVID‐19 in the Stockholm region, Sweden. ACs are proven to reduce the risk of complications and mortality from COVID‐19 among patients of other ages and settings, but there is limited scientific evidence underpinning this practice in the NH setting. Methods This matched cohort study included 182 NH residents in the Stockholm Region diagnosed with COVID‐19 in March–May 2020. The main exposure was any AC treatment. Exposed (n = 91), 49% prevalent (pre‐COVID‐19 diagnosis) AC and 51% incident AC were compared with unexposed controls (n = 91). The outcome was 28‐days all‐cause mortality after COVID‐19 infection. The mortality odds ratios (OR) were assessed using logistic regression, adjusted for age, sex, multimorbidity, and mobility, also stratified by incident or prevalent AC‐type, age group, and sex. Results Of the 182 individuals diagnosed with COVID‐19 (median age 88 years, 68% women), 39% died within 28 days after diagnosis. Use of either incident or prevalent AC was associated with a reduced, adjusted 28‐day mortality (OR[95% CI]: 0.31[0.16–0.62]). In stratified analyses, the association was significant in both age groups: 70–89 (OR: 0.37 [0.15–0.89]) and 90–99 years of age (OR: 0.22 [0.07–0.65]. In sex‐stratified analysis, the AC‐lowering effect was significant in women only (OR: 0.28[0.11–0.67]). In the analyses stratified by AC type, the mortality‐lowering effect was observed for both prevalent AC (OR: 0.35[0.12–0.99]) and incident AC (OR: 0.29[0.11–0.76]). Conclusions Both prevalent and incident use of ACs in prophylactic dosing was associated with reduced 28‐day mortality among older individuals with COVID‐19 in a NH setting. The effect was seen across age‐strata and in women. The findings present new insight in best practice for individuals diagnosed with COVID‐19 in the NH setting.

Background: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. Objectives: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. Methods: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50–64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. Results: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (

Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using

Sustainable production of drinking water requires safe and efficient production, operation, and maintenance of the entire production line. Rapid gravity granular filters in water production require periodic backwash to ensure water quantity and quality. Therefore, an efficient backwash strategy plays a key role in ensuring a sustainable operation of the filters. In this study, a real-time monitoring method based on electrical resistivity tomography has been developed and tested at full scale for a period of six months in a rapid gravity granular filter during drinking water production. It provides proof of concept for a developed equipment and monitoring strategy within the given production environment. The time series of collected data, with different depth sensitivities of the upper 40 cm filter bed, demonstrates the temporal and spatial resolution capability of the method. Results show temporal development related to dynamic operation and backwash which in this study is combined with snapshot diagnostic tools and operational parameters to increase the spatial understanding of the active processes within the filter. These results suggest electrical resistivity tomography to be a suitable method for monitoring backwash efficiency. HIGHLIGHTS Spatial variation within rapid sand filtration is monitored in real time.; The applied electrical resistivity tomography monitoring strategy reveals vertical and temporal variations directly related to the operational and physical state of the filter.; Good and bad backwash efficiency can be differentiated based on the real-time monitoring data.;

Abstract Introduction In order to fulfill the enormous potential of digital health in the healthcare sector, digital health must become an integrated part of medical education. We aimed to investigate which knowledge, skills and attitudes should be included in a digital health curriculum for medical students through a scoping review and Delphi method study. Methods We conducted a scoping review of the literature on digital health relevant for medical education. Key topics were split into three sub-categories: knowledge (facts, concepts, and information), skills (ability to carry out tasks) and attitudes (ways of thinking or feeling). Thereafter, we used a modified Delphi method where experts rated digital health topics over two rounds based on whether topics should be included in the curriculum for medical students on a scale from 1 (strongly disagree) to 5 (strongly agree). A predefined cut-off of ≥4 was used to identify topics that were critical to include in a digital health curriculum for medical students. Results The scoping review resulted in a total of 113 included articles, with 65 relevant topics extracted and included in the questionnaire. The topics were rated by 18 experts, all of which completed both questionnaire rounds. A total of 40 (62%) topics across all three sub-categories met the predefined rating cut-off value of ≥4. Conclusion An expert panel identified 40 important digital health topics within knowledge, skills, and attitudes for medical students to be taught. These can help guide medical educators in the development of future digital health curricula.

Background: Ambient fine particulate matter (PM2.5) causes millions of deaths every year worldwide. Identification of the most harmful types of PM2.5 would facilitate efficient prevention strategies. Objectives: The aim of this study was to investigate associations between components of PM2.5 and mortality in a nation-wide Danish population. Methods: Our study base was Danes born 1921–1985 and aged 30–85 years, who were followed up for mortality from 1991 to 2015. We included 678,465 natural cause mortality cases and selected five age, sex and calendar time matched controls to each case from the study base. We retrieved the address history of the study population from Danish registries and assessed five-year average concentrations of eight PM2.5 components using deterministic Chemistry-Transport Models air pollution models. We estimated mortality rate ratios (MRRs) by conditional logistic regression and adjusted for socio-demographical factors at individual and neighborhood level. Results: Single pollutant models showed the strongest associations between natural cause mortality and an interquartile increase in sulfate particles (SO4−-) (MRR: 1.123; 95 % CI: 1.100–1.147 per 1.5 µg/m3) and secondary organic aerosol (SOA) (MRR: 1.054; 95 % CI: 1.048–1.061 per 0.050 µg/m3). Two-pollutant models showed robust associations between SO4−− and SOA and natural cause mortality. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality. Conclusion: This nation-wide study found robust associations between natural cause mortality and SO4−− particles and SOA, which is in line with the results of previous studies. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality.

BackgroundAlthough studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines.MethodsWe present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies.ResultsThere was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living

Objective: Air pollution, road traffic noise and lack of greenness coexist in urban environments and have all been associated with type 2 diabetes. We aimed to investigate how these co-exposures were associated with type 2 diabetes in a multi-exposure perspective. Methods: We estimated 5-year residential mean exposure to fine particles (PM2.5), ultrafine particles (UFP), elemental carbon (EC), nitrogen dioxide (NO2) and road traffic noise at the most (LdenMax) and least (LdenMin) exposed facade for all persons aged > 50 years living in Denmark in 2005 to 2017. For each air pollutant, we estimated total concentrations and traffic contributions. Based on land use maps, we estimated proportion of green and non-green space within 150 and 1000 m of all residences. In total, 1.9 million persons were included and 128,358 developed type 2 diabetes during follow-up. We performed analyses using Cox proportional hazards models, with adjustment for individual and neighborhood-level sociodemographic co-variates. Results: In single-pollutant models, all air pollutants, noise and lack of green space were associated with higher risk of diabetes. In two-, three- and four-pollutant analyses of the air pollutants, only UFP and NO2 remained associated with higher diabetes risk in all models. LdenMax, LdenMin and the two proxies of green space remained associated with diabetes in two-pollutant models of, respectively, noise and green space. In a multi-pollutant analysis, we found hazard ratios (95 % confidence intervals) per interquartile range of 1.021 (1.005; 1.038) for UFP, 1.012 (0.996; 1.028) for NO2, 1.022 (1.012; 1.033) for LdenMin, 1.013 (1.004; 1.022) for LdenMax, and 1.038 (1.031; 1.044) and 1.018 (1.010; 1.025) for lack of green space within, respectively, 150 m and 1000 m, and a cumulative risk index of 1.131 (1.113; 1.149). Conclusions: Air pollution, road traffic noise and lack of green space were independently associated with higher risk of type 2 diabetes.

Summary: Introduction: Diagnostic confirmation of SARS-CoV-2 by self-collection of specimens is a reliable method compared with healthcare worker collected samples. Citizens’ preferences for collection methods are unknown, but at-home collection could have several advantages. Methods: This study investigated the preference for guided at-home self-collection versus at-hospital specimen collection by healthcare workers. Results: Among the 3709 participants, at-home swab collection was the preferred setting for 2362 (63.7%) compared with 1347 (36.3%) reporting a preference for an at-hospital swabbing procedure. Conclusion: A high preference for guided at-home self-collection of oropharyngeal/nasal SARS-CoV-2 specimens exists and could be a future norm beyond COVID-19.

Background: The majority of studies have shown higher greenness exposure associated with reduced mortality risks, but few controlled for spatially correlated air pollution and traffic noise exposures. We aim to address this research gap in the ELAPSE pooled cohort. Methods: Mean Normalized Difference Vegetation Index (NDVI) in a 300-m grid cell and 1-km radius were assigned to participants’ baseline home addresses as a measure of surrounding greenness exposure. We used Cox proportional hazards models to estimate the association of NDVI exposure with natural-cause and cause-specific mortality, adjusting for a number of potential confounders including socioeconomic status and lifestyle factors at individual and area-levels. We further assessed the associations between greenness exposure and mortality after adjusting for fine particulate matter (PM2.5), nitrogen dioxide (NO2) and road traffic noise. Results: The pooled study population comprised 327,388 individuals who experienced 47,179 natural-cause deaths during 6,374,370 person-years of follow-up. The mean NDVI in the pooled cohort was 0.33 (SD 0.1) and 0.34 (SD 0.1) in the 300-m grid and 1-km buffer. In the main fully adjusted model, 0.1 unit increment of NDVI inside 300-m grid was associated with 5% lower risk of natural-cause mortality (Hazard Ratio (HR) 0.95 (95% CI: 0.94, 0.96)). The associations attenuated after adjustment for air pollution [HR (95% CI): 0.97 (0.96, 0.98) adjusted for PM2.5; 0.98 (0.96, 0.99) adjusted for NO2]. Additional adjustment for traffic noise hardly affected the associations. Consistent results were observed for NDVI within 1-km buffer. After adjustment for air pollution, NDVI was inversely associated with diabetes, respiratory and lung cancer mortality, yet with wider 95% confidence intervals. No association with cardiovascular mortality was found. Conclusions: We found a significant inverse association between surrounding greenness and natural-cause mortality, which remained after adjusting for spatially correlated air pollution and traffic noise.

Background: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure. Methods: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5–16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority. Results: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors. Conclusions: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.

Abstract Background Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15–20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. Methods This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, “low intensity” group) or an intervention (“high-intensity” group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and “buddy-matching” (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. Discussion The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. Trial registration ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019

Abstract Background Inconclusive evidence has suggested a possible link between air pollution and central nervous system (CNS) tumors. We investigated a range of air pollutants in relation to types of CNS tumors. Methods We identified all (n = 21,057) intracranial tumors in brain, meninges and cranial nerves diagnosed in Denmark between 1989 and 2014 and matched controls on age, sex and year of birth. We established personal 10-year mean residential outdoor exposure to particulate matter

Nature-based solutions (NBS) can protect, manage and restore natural or modified ecosystems. They are a multidisciplinary, integrated approach to address societal challenges and some natural hazards effectively and adaptively, simultaneously providing human well-being and biodiversity benefits. NBS applications can be easily noticed in circular cities, establishing an urban system that is regenerative and accessible. This paper aims to offer a review on NBS for urban water management from the literature and some relevant projects running within the COST Action ‘Implementing nature-based solutions for creating a resourceful circular city’. The method used in the study is based on a detailed tracking of specific keywords in the literature using Google Scholar, ResearchGate, Academia.edu, ScienceDirect and Scopus. Based on this review, three main applications were identified: (i) flood and drought protection; (ii) the water-food-energy nexus; and (iii) water purification. The paper shows that NBS provide additional benefits, such as improving water quality, increasing biodiversity, obtaining social co-benefits, improving urban microclimate, and the reduction of energy consumption by improving indoor climate. The paper concludes that a systemic change to NBS should be given a higher priority and be preferred over conventional water infrastructure.

Summary: Background: Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). Methods: In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000–11; follow-up until 2011–17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis. Findings: We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2·5, NO2, and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021–1·085) per 5 μg/m3 increment in PM2·5, 1·044 (1·019–1·069) per 10 μg/m3 NO2, and 1·039 (1·018–1·059) per 0·5 × 10−5/m black carbon. Associations with PM2·5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2·5 (10 μg/m3) and NO2 (40 μg/m3) were 1·078 (1·046–1·111) per 5 μg/m3 PM2·5 and 1·049 (1·024–1·075) per 10 μg/m3 NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032–1·092) for exposure lower than 1·5× 10−5/m, and 1·081 (0·966–1·210) for exposure lower than 1·0× 10−5/m. Interpretation: Long-term exposure to concentrations of PM2·5 and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions. Funding: Health Effects Institute.

Abstract Objective To study if treatment with triheptanoin, a 7‐carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen‐dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxidation. We hypothesized that triheptanoin metabolism generates substrates for the TCA, which potentially boosts fat oxidation and improves exercise tolerance in McArdle disease. Methods Double‐blind, placebo‐controlled, crossover study in patients with McArdle disease completing two treatment periods of 14 days each with a triheptanoin or placebo diet (1 g/kg/day). Primary outcome was change in mean heart rate during 20 min submaximal exercise on a cycle ergometer. Secondary outcomes were change in peak workload and oxygen uptake along with changes in blood metabolites and respiratory quotients. Results Nineteen of 22 patients completed the trial. Malate levels rose on triheptanoin treatment versus placebo (8.0 ± SD2.3 vs. 5.5 ± SD1.8 µmol/L, P

Air pollutants such as NO2 and PM2.5 have consistently been linked to mortality, but only few previous studies have addressed associations with long-term exposure to black carbon (BC) and ozone (O3).We investigated the association between PM2.5, PM10, BC, NO2, and O3 and mortality in a Danish cohort of 49,564 individuals who were followed up from enrollment in 1993–1997 through 2015. Residential address history from 1979 onwards was combined with air pollution exposure obtained by the state-of-the-art, validated, THOR/AirGIS air pollution modelling system, and information on residential traffic noise exposure, lifestyle and socio-demography.We observed higher risks of all-cause as well as cardiovascular disease (CVD) mortality with higher long-term exposure to PM2.5, PM10, BC, and NO2. For PM2.5 and CVD mortality, a hazard ratio (HR) of 1.29 (95% CI: 1.13–1.47) per 5 μg/m3 was observed, and correspondingly HRs of 1.16 (95% CI: 1.05–1.27) and 1.11 (95% CI: 1.04–1.17) were observed for BC (per 1 μg/m3) and NO2 (per 10 μg/m3), respectively. Adjustment for noise gave slightly lower estimates for the air pollutants and CVD mortality. Inverse relationships were observed for O3. None of the investigated air pollutants were related to risk of respiratory mortality. Stratified analyses suggested that the elevated risks of CVD and all-cause mortality in relation to long-term PM, NO2 and BC exposure were restricted to males.This study supports a role of PM, BC, and NO2 in all-cause and CVD mortality independent of road traffic noise exposure. Keywords: Particulate matter, NO2, Black carbon, Ozone, CVD, Mortality, Epidemiology

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50–64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 μg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 – 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 – 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.

Background: We evaluated methods for the analysis of multi-level survival data using a pooled dataset of 14 cohorts participating in the ELAPSE project investigating associations between residential exposure to low levels of air pollution (PM2.5 and NO2) and health (natural-cause mortality and cerebrovascular, coronary and lung cancer incidence). Methods: We applied five approaches in a multivariable Cox model to account for the first level of clustering corresponding to cohort specification: (1) not accounting for the cohort or using (2) indicator variables, (3) strata, (4) a frailty term in frailty Cox models, (5) a random intercept under a mixed Cox, for cohort identification. We accounted for the second level of clustering due to common characteristics in the residential area by (1) a random intercept per small area or (2) applying variance correction. We assessed the stratified, frailty and mixed Cox approach through simulations under different scenarios for heterogeneity in the underlying hazards and the air pollution effects. Results: Effect estimates were stable under approaches used to adjust for cohort but substantially differed when no adjustment was applied. Further adjustment for the small area grouping increased the effect estimates’ standard errors. Simulations confirmed identical results between the stratified and frailty models. In ELAPSE we selected a stratified multivariable Cox model to account for between-cohort heterogeneity without adjustment for small area level, due to the small number of subjects and events in the latter. Conclusions: Our study supports the need to account for between-cohort heterogeneity in multi-center collaborations using pooled individual level data.

Background/aim: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence. Methods: The “Effects of Low-level Air Pollution: a Study in Europe” (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O3) to assign exposure to cohort participants’ residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines. Results: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O3 (warm season) were 24.2 µg/m3 (19.5, 29.7), 15.4 µg/m3 (12.8, 17.3), 1.6 10−5m−1 (1.3, 1.8), and 86.6 µg/m3 (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m3). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m3. We did not observe associations between NO2, BC or O3 and lung cancer incidence. Conclusions: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.

Background: Air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD), but evidence is sparse and inconsistent. Objectives: We examined the association between long-term exposure to low-level air pollution and COPD incidence. Methods: Within the ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE) study, we pooled data from three cohorts, from Denmark and Sweden, with information on COPD hospital discharge diagnoses. Hybrid land use regression models were used to estimate annual mean concentrations of particulate matter with a diameter

This paper proposes and demonstrates, in full scale, a novel type of energy geostructure (“the Climate Road”) that combines a ground-source heat pump (GSHP) with a sustainable urban drainage system (SUDS) by utilizing the gravel roadbed simultaneously as an energy source and a rainwater retarding basin. The Climate Road measures 50 m × 8 m × 1 m (length, width, depth, respectively) and has 800 m of geothermal piping embedded in the roadbed, serving as the heat collector for a GSHP that supplies a nearby kindergarten with domestic hot water and space heating. Model analysis of operational data from 2018–2021 indicates sustainable annual heat production levels of around 0.6 MWh per meter road, with a COP of 2.9–3.1. The continued infiltration of rainwater into the roadbed increases the amount of extractable heat by an estimated 17% compared to the case of zero infiltration. Using the developed model for scenario analysis, we find that draining rainwater from three single-family houses and storing 30% of the annual heating consumption in the roadbed increases the predicted extractable energy by 56% compared to zero infiltration with no seasonal energy storage. The Climate Road is capable of supplying three new single-family houses with heating, cooling, and rainwater management year-round.

Background: The etiology of childhood cancer is poorly understood. The role of environmental factors, including air pollution (AP) exposure, has been addressed previously, but results so far have been inconclusive. In this study, we investigate the association between long-term AP exposures in relation to childhood cancer subtypes in Denmark (1981–2013). Methods: We conducted a nationwide register-based case-control study. We identified 7745 incident cases of childhood cancers (

Background: Studies have shown higher mortality in association with exposure to air pollution. We investigated this association with focus on differences between socioeconomic groups. Methods: We included all Danes born between 1921 and 1985 aged 30–85 years from 1991 to 2015 (N = 4,401,348). We applied a nested case-control design and identified those who died during follow-up and selected five controls per case. We modelled NO2, fine particulate matter (PM2·5), black carbon (BC) particles, and ozone (O3) as five-year average concentrations at the residential addresses of 672,895 all natural cause mortality cases and 3,426,533 controls in conditional logistic regression with adjustment for individual and neighbourhood level socio-demographic variables. Findings: In single pollutant models, a 10 μg/m3 (BC: 1 μg/m3) increase in NO2, PM2·5, BC, and O3 was associated with natural cause mortality rate ratios (MRR) of 1·05 (95% confidence interval 1·04–1·06), 1·08 (1·04–1·13), 1·05 (1·02–1·08), and 0·96 (0·95–0·97), respectively. The patterns were similar for respiratory disease and lung cancer mortality. O3 was associated with higher risk of CVD mortality. The rate differences for a unit increase in PM2·5, NO2, and BC were largest among those with the lowest income; this pattern was not detected when considering the relative risk measure, MRR. Interpretation: Long-term concentration of air pollution at the residence was associated with higher natural cause mortality in the Danish population and the strength of the association differed by socioeconomic group. We recommend that future studies express socioeconomic differences in absolute rather than relative risk.

Background: Air pollution is an established carcinogen. Evidence for an association with brain tumors is, however, inconclusive. We investigated if individual particulate matter constituents were associated with brain tumor risk. Methods: From comprehensive national registers, we identified all (n = 12 928) brain tumor cases, diagnosed in Denmark in the period 1989–2014, and selected 22 961 controls, matched on age, sex and year of birth. We established address histories and estimated 10-year mean residential outdoor concentrations of particulate matter

Noise from wind turbines (WTs) has been reported more annoying than traffic noise at similar levels, and concerns have been raised about whether WT noise (WTN) can increase risk for cardiovascular disease. We aimed to investigate if long-term exposure to WTN increases risk for hypertension, estimated as redemption of prescriptions for antihypertensive drugs. We identified all Danish dwellings within a radius of 20 WT heights from a WT and 25% randomly selected dwellings within 20–40 WT heights radius. Using data on WT type and hourly wind conditions at each WT, we estimated hourly outdoor (10–10,000 Hz) and low frequency (LF: 10–160 Hz) indoor WTN for all dwellings, and aggregated it as long-term nighttime running means. From nationwide registries, we identified 535,675 persons age 25–85 years living in these dwellings for >1 year from 1996 to 2013, of whom 83,729 fulfilled our case definition of redeeming ≥2 prescriptions and ≥180 defined daily doses of antihypertensive drugs within a year. Data were analyzed using Poisson regression according to categories of WTN exposure and adjustment for individual and area-level covariates. We found no associations between 5-year mean exposure to WTN during night and redemption of antihypertensives, with hazard ratios (HR) of 0.91 (95% confidence intervals (CI): 0.78–1.06) for outdoor WTN ≥ 42 dB(A) and of 1.06 (CI: 0.83–1.35) for indoor LF WTN ≥ 15 dB(A) when compared to the reference WTN levels (

Introduction: High arsenic concentration in drinking water is associated with a higher incidence rate of stroke, but only few studies have investigated an association with arsenic in drinking water at low concentration (

OBJECTIVES: Exposure to traffic noise and air pollution is suspected to increase susceptibility to viral infections – the main triggering factor for febrile seizures. No studies have examined these two exposures in relation to febrile seizures. We aimed to investigate whether exposure to road traffic noise and air pollution are associated with risk of febrile seizures in childhood. METHODS: From our study base of 51 465 singletons from a national birth cohort, we identified 2175 cases with febrile seizures using a nationwide registry. Residential address history from conception to six years of age were found in national registers, and road traffic noise (L_den) and air pollution (NO_2) were modeled for all addresses. Analyses were done using Cox proportional hazard model with adjustment for potential confounders, including mutual exposure adjustment. RESULTS: An interquartile range (IQR) increase in childhood exposure to road traffic noise and air pollution was associated with an 11% [incidence rate ratio (IRR) 1.11, 95% confidence interval (CI) 1.04–1.19) and 5% (IRR 1.05, 95% CI 1.02–1.07) higher risk for febrile seizures, respectively, after adjustment for potential confounders. Weaker tendencies were seen for pregnancy exposure. In models with mutual exposure adjustment, the estimates were slightly lower, with IRR of 1.08 (95% CI 1.00–1.16) and 1.03 (95% CI 0.99–1.06) per IQR increase in childhood exposure to road traffic noise and air pollution, respectively. CONCLUSIONS: This study suggests that residential exposure to road traffic noise and air pollution is associated with higher risk for febrile seizures.